Associations Between Vitamin D Deficiency/Insufficiency and Depression Expose Health Disparities in Older Rural West Texans: A Project FRONTIER Study.

OBJECTIVE: To determine associations between Vitamin D (VD) levels and clinical depression through the Geriatric Depression Scale (GDS) and its questions and subdomains, stratified by demographics and Hispanic/Latino ethnicity (HLE). DESIGN, SETTING, AND PARTICIPANTS: A cohort of 299 Project FRONTIER participants aged 62.6 ± 11.7 years old, 70.9% female, and 40.5% HLE were used. Standard correlation and regression analyses were employed. MEASUREMENTS: The main outcome measures were VD (serum 25(OH)-VD) level, GDS-30 (30-item questionnaire), GDS-30 subfactors and questions, and HLE status. VD categories were defined as VD deficiency (VDD; ≤20 ng/mL), VD insufficiency (VDI; 21-29 ng/mL), VD sufficiency (30-38 ng/mL) and high VD sufficiency (>38 ng/mL). RESULTS: The majority (61.5%) of samples fell into VDD/VDI categories. A significant negative association was found between VD level and GDS-30 total score. VD level was negatively correlated with Dysphoria and Meaninglessness GDS-30 subfactors. Although GDS subfactors were similar between HLE and non-HLE groups, VD levels were significantly lower in HLE samples. Finally, HLE/non-HLE groups were differentially stratified across VD categories. Only 4% of HLEs fell into the high VD sufficient category, suggesting low VD supplementation. CONCLUSION: A significant negative association between VD level and depressive symptoms was revealed in our aging Project FRONTIER participants. HLE individuals were overrepresented in VDD/VDI samples, and VDD/VDI was associated primarily with the Dysphoria GDS subdomain. Regression analysis predicted high VD sufficiency (95.5 ng/mL) to be associated with no depressive symptoms (GDS=0). Our results underscore troubling disparities in VD-related depressive symptoms between HLE and non-HLE populations.

Pain and aging: A unique challenge in neuroinflammation and behavior.

Chronic pain is one of the most common, costly, and potentially debilitating health issues facing older adults, with attributable costs exceeding $600 billion annually. The prevalence of pain in humans increases with advancing age. Yet, the contributions of sex differences, age-related chronic inflammation, and changes in neuroplasticity to the overall experience of pain are less clear, given that opposing processes in aging interact. This review article examines and summarizes pre-clinical research and clinical data on chronic pain among older adults to identify knowledge gaps and provide the base for future research and clinical practice. We provide evidence to suggest that neurodegenerative conditions engender a loss of neural plasticity involved in pain response, whereas low-grade inflammation in aging increases CNS sensitization but decreases PNS sensitivity. Insights from preclinical studies are needed to answer mechanistic questions. However, the selection of appropriate aging models presents a challenge that has resulted in conflicting data regarding pain processing and behavioral outcomes that are difficult to translate to humans.

Pomegranate peel extract is an effective agent against MDR bacteria.

Multidrug-resistant (MDR) bacteria are one of the major public health threats facing humanity. Infections with MDR strains are difficult or impossible to treat with standard antibiotics leading to severe illnesses and even deaths. The spread of MDR bacteria has necessitated the search for alternative approaches that tackle MDR pathogens. Natural plants can be utilized as alternative therapeutic agents against the rise of MDR bacteria. In this study, we aimed to assess the antimicrobial activity of pomegranate peel extracts (PPE) against MDR clinical isolates. A total of 9 clinical isolates (8 MDR and 1 non-MDR clinical isolates) were collected and examined for their susceptibility to PPE. Using the zone of inhibition assay, 4 isolates (S. aureus, three MRSA isolates, Vancomycin-resistant Enterococci (VRE), and Acinetobacter baumannii) were sensitive to PPE. In Broth assay, 4 mg/ml PPE significantly reduced the growth (S. aureus, three MRSA isolates, Vancomycin-resistant Enterococci (VRE), and Acinetobacter baumannii), while 40 mg/ml PPE either significantly reduced or completely inhibited the growth of the isolates. The minimum bactericidal concentration (MBC) of PPE against S. aureus and MRSA-88 was 10 mg/ml. This study showed the potential of PPE as an alternative compound for treating infections caused by PPE-sensitive MDR bacteria.

The Role of Red Cell Distribution Width as a Prognostic Marker in Chronic Liver Disease: A Literature Review.

Liver disease is one of the leading public health problems faced by healthcare practitioners regularly. As such, there has been a search for an inexpensive, readily available, non-invasive marker to aid in monitoring and prognosticating hepatic disorders. Recently, red blood cell distribution width (RDW) has been found to be associated with various inflammatory conditions with implications for its use as a potential marker for assessing disease progression and prognosis in multiple conditions. Multiple factors effect red blood cell production whereby a dysfunction in any process can lead to anisocytosis. Furthermore, a chronic inflammatory state leads to increased oxidative stress and produces inflammatory cytokines causing dysregulation and increased intracellular uptake and use of both iron and vitamin B12, which leads to a reduction in erythropoiesis causing an increase in RDW. This literature review reviews in-depth pathophysiology that may lead to an increase in RDW and its potential correlation with chronic liver diseases, including hepatitis B, hepatitis C, hepatitis E, non-alcoholic fatty liver disease, autoimmune hepatitis, primary biliary cirrhosis, and hepatocellular carcinoma. In our review, we examine the use of RDW as a prognostic and predictive marker for hepatic injury and chronic liver disease.

Consequences of NaCT/SLC13A5/mINDY deficiency: good versus evil, separated only by the blood-brain barrier.

NaCT/SLC13A5 is a Na+-coupled transporter for citrate in hepatocytes, neurons, and testes. It is also called mINDY (mammalian ortholog of 'I'm Not Dead Yet' in Drosophila). Deletion of Slc13a5 in mice leads to an advantageous phenotype, protecting against diet-induced obesity, and diabetes. In contrast, loss-of-function mutations in SLC13A5 in humans cause a severe disease, EIEE25/DEE25 (early infantile epileptic encephalopathy-25/developmental epileptic encephalopathy-25). The difference between mice and humans in the consequences of the transporter deficiency is intriguing but probably explainable by the species-specific differences in the functional features of the transporter. Mouse Slc13a5 is a low-capacity transporter, whereas human SLC13A5 is a high-capacity transporter, thus leading to quantitative differences in citrate entry into cells via the transporter. These findings raise doubts as to the utility of mouse models to evaluate NaCT biology in humans. NaCT-mediated citrate entry in the liver impacts fatty acid and cholesterol synthesis, fatty acid oxidation, glycolysis, and gluconeogenesis; in neurons, this process is essential for the synthesis of the neurotransmitters glutamate, GABA, and acetylcholine. Thus, SLC13A5 deficiency protects against obesity and diabetes based on what the transporter does in hepatocytes, but leads to severe brain deficits based on what the transporter does in neurons. These beneficial versus detrimental effects of SLC13A5 deficiency are separable only by the blood-brain barrier. Can we harness the beneficial effects of SLC13A5 deficiency without the detrimental effects? In theory, this should be feasible with selective inhibitors of NaCT, which work only in the liver and do not get across the blood-brain barrier.

Amyloid Beta in Aging and Alzheimer's Disease.

Alzheimer's disease (AD), is a progressive neurodegenerative disease that affects behavior, thinking, learning, and memory in elderly individuals. AD occurs in two forms, early onset familial and late-onset sporadic; genetic mutations in PS1, PS2, and APP genes cause early onset familial AD, and a combination of lifestyle, environment and genetic factors causes the late-onset sporadic form of the disease. However, accelerated disease progression is noticed in patients with familial AD. Disease-causing pathological changes are synaptic damage, and mitochondrial structural and functional changes, in addition to increased production and accumulation of phosphorylated tau (p-tau), and amyloid beta (Aß) in the affected brain regions in AD patients. Aß is a peptide derived from amyloid precursor protein (APP) by proteolytic cleavage of beta and gamma secretases. APP is a glycoprotein that plays a significant role in maintaining neuronal homeostasis like signaling, neuronal development, and intracellular transport. Aß is reported to have both protective and toxic effects in neurons. The purpose of our article is to summarize recent developments of Aß and its association with synapses, mitochondria, microglia, astrocytes, and its interaction with p-tau. Our article also covers the therapeutic strategies that reduce Aß toxicities in disease progression and discusses the reasons for the failures of Aß therapeutics.

Binding of Citrate-Fe3+ to Plastic Culture Dishes, an Artefact Useful as a Simple Technique to Screen for New Iron Chelators.

NaCT mediates citrate uptake in the liver cell line HepG2. When these cells were exposed to iron (Fe3+), citrate uptake/binding as monitored by the association of [14C]-citrate with cells increased. However, there was no change in NaCT expression and function, indicating that NaCT was not responsible for this Fe3+-induced citrate uptake/binding. Interestingly however, the process exhibited substrate selectivity and saturability as if the process was mediated by a transporter. Notwithstanding these features, subsequent studies demonstrated that the iron-induced citrate uptake/binding did not involve citrate entry into cells; instead, the increase was due to the formation of citrate-Fe3+ chelate that adsorbed to the cell surface. Surprisingly, the same phenomenon was observed in culture wells without HepG2 cells, indicating the adsorption of the citrate-Fe3+ chelate to the plastic surface of culture wells. We used this interesting phenomenon as a simple screening technique for new iron chelators with the logic that if another iron chelator is present in the assay system, it would compete with citrate for binding to Fe3+ and prevent the formation and adsorption of citrate-Fe3+ to the culture well. This technique was validated with the known iron chelators deferiprone and deferoxamine, and with the bacterial siderophore 2,3-dihydroxybenzoic acid and the catechol carbidopa.

Global Impact of COVID-19 on Colorectal Cancer Screening: Current Insights and Future Directions.

The coronavirus disease 2019 (COVID-19) pandemic has brought significant challenges to many aspects of healthcare delivery since the first reported case in early December 2019. Once in the body, SARS-CoV-2 can spread to other digestive organs, such as the liver, because of the presence of ACE2 receptors. Colorectal cancer (CRC) remains the second-leading cause of death in the United States (US). Therefore, individuals are routinely screened using either endoscopic methods (i.e., flexible sigmoidoscopy and colonoscopy) or stool-based tests, as per the published guidelines. At the beginning of the COVID-19 pandemic, the Centers for Medicare and Medicaid Services (CMS) recommended that all non-urgent surgical and medical procedures, including screening colonoscopies, be delayed until the pandemic stabilization. This article aims to review the impact of COVID-19 on CRC screening.

A Reappraisal of Oxandrolone in Burn Management.

Objective: Burn injuries remain among the most severe traumatic injuries globally. With the discovery of cortisol, the use of steroids has become an essential therapy for the management of inflammatory and metabolic conditions. Several studies have shown the steroid oxandrolone improves burn injuries through stimulating anabolic and reducing catabolic processes. In this review, we examine the efficacy and applications of oxandrolone with regard to burn management and treatment. Data Sources: A literature search was performed using the PubMed database from January 1990 to May 2020 to identify articles on oxandrolone and burn management. A total of 18 studies were included in our review. Study Selection and Criteria: The keywords used in our search strategy for PubMed included "oxandrolone" and "burns." Data Synthesis: The main benefit of oxandrolone is the improved long-term lean body, protein, and bone mineral mass of burn patients. In addition, 3 separate meta-analyses showed oxandrolone shortened length of hospital stay, donor-site healing time, reduced weight loss, and net protein loss. However, oxandrolone therapy did not affect mortality, infection, or liver function. Conclusion: Oxandrolone remains an effective therapy for reducing the hypermetabolic response and comorbidities from burn injuries. Future clinical trials are needed using larger sample sizes and long-term follow-up to determine whether oxandrolone in the context of rehabilitation programs can reduce mortality, lower treatment costs, and improve function outcomes among burn patients.

Functional analysis of a species-specific inhibitor selective for human Na+-coupled citrate transporter (NaCT/SLC13A5/mINDY).

The Na+-coupled citrate transporter (NaCT/SLC13A5/mINDY) in the liver delivers citrate from the blood into hepatocytes. As citrate is a key metabolite and regulator of multiple biochemical pathways, deletion of Slc13a5 in mice protects against diet-induced obesity, diabetes, and metabolic syndrome. Silencing the transporter suppresses hepatocellular carcinoma. Therefore, selective blockers of NaCT hold the potential to treat various diseases. Here we report on the characteristics of one such inhibitor, BI01383298. It is known that BI01383298 is a high-affinity inhibitor selective for human NaCT with no effect on mouse NaCT. Here we show that this compound is an irreversible and non-competitive inhibitor of human NaCT, thus describing the first irreversible inhibitor for this transporter. The mouse NaCT is not affected by this compound. The inhibition of human NaCT by BI01383298 is evident for the constitutively expressed transporter in HepG2 cells and for the ectopically expressed human NaCT in HEK293 cells. The IC50 is ∼100 nM, representing the highest potency among the NaCT inhibitors known to date. Exposure of HepG2 cells to this inhibitor results in decreased cell proliferation. We performed molecular modeling of the 3D-structures of human and mouse NaCTs using the crystal structure of a humanized variant of VcINDY as the template, and docking studies to identify the amino acid residues involved in the binding of citrate and BI01383298. These studies provide insight into the probable bases for the differential effects of the inhibitor on human NaCT versus mouse NaCT as well as for the marked species-specific difference in citrate affinity.

Clinical Insights into the Gastrointestinal Manifestations of COVID-19.

The month of December 2019 became a critical part of the time of humanity when the first case of coronavirus disease 2019 (COVID-19) was reported in the Wuhan, Hubei Province in China. As of April 13th, 2020, there have been approximately 1.9 million cases and 199,000 deaths across the world, which were associated with COVID-19. The COVID-19 is the seventh coronavirus to be identified to infect humans. In the past, Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome were the two coronaviruses that infected humans with a high fatality, particularly among the elderly. Fatalities due to COVID-19 are higher in patients older than 50 years of age or those with multimorbid conditions. The COVID-19 is mainly transmitted through respiratory droplets, with the most common symptoms being high fever, cough, myalgia, atypical symptoms included sputum production, headache, hemoptysis and diarrhea. However, the incubation period can range from 2 to 14 days without any symptoms. It is particularly true with gastrointestinal (GI) symptoms in which patients can still shed the virus even after pulmonary symptoms have resolved. Given the high percentage of COVID-19 patients that present with GI symptoms (e.g., nausea and diarrhea), screening patients for GI symptoms remain essential. Recently, cases of fecal-oral transmission of COVID-19 have been confirmed in the USA and China, indicating that the virus can replicate in both the respiratory and digestive tract. Moreover, the epidemiology, clinical characteristics, diagnostic procedures, treatments and prevention of the gastrointestinal manifestations of COVID-19 remain to be elucidated.

Evaluation of standard and semantically-augmented distance metrics for neurology patients.

BACKGROUND: Patient distances can be calculated based on signs and symptoms derived from an ontological hierarchy. There is controversy as to whether patient distance metrics that consider the semantic similarity between concepts can outperform standard patient distance metrics that are agnostic to concept similarity. The choice of distance metric can dominate the performance of classification or clustering algorithms. Our objective was to determine if semantically augmented distance metrics would outperform standard metrics on machine learning tasks. METHODS: We converted the neurological findings from 382 published neurology cases into sets of concepts with corresponding machine-readable codes. We calculated patient distances by four different metrics (cosine distance, a semantically augmented cosine distance, Jaccard distance, and a semantically augmented bipartite distance). Semantic augmentation for two of the metrics depended on concept similarities from a hierarchical neuro-ontology. For machine learning algorithms, we used the patient diagnosis as the ground truth label and patient findings as machine learning features. We assessed classification accuracy for four classifiers and cluster quality for two clustering algorithms for each of the distance metrics. RESULTS: Inter-patient distances were smaller when the distance metric was semantically augmented. Classification accuracy and cluster quality were not significantly different by distance metric. CONCLUSION: Although semantic augmentation reduced inter-patient distances, we did not find improved classification accuracy or improved cluster quality with semantically augmented patient distance metrics when applied to a dataset of neurology patients. Further work is needed to assess the utility of semantically augmented patient distances.

Association of Hypertension and Hyperthyroidism in a Subspecialty Clinic and a National Database.

OBJECTIVE: Hypertension can cause significant morbidity and reduced life expectancy. Most patients with hypertension have primary hypertension; however, 10% to 15% have secondary hypertension. Endocrine disorders as a secondary cause occur in approximately 10% of patients with secondary hypertension, and thyroid disorders account for approximately 1% of all patients with hypertension. The identification of patients with hyperthyroidism has important benefits for these particular patients. The objective of this study was to examine the occurrence of high blood pressure in patients with hyperthyroidism. METHODS: We reviewed the clinical information available from 414 new patients referred to an endocrinology clinic in west Texas for evaluation of hyperthyroidism. The final cohort included 96 patients who had both thyroid laboratory tests and blood pressure measurements at the time of their clinic visit. We also examined this relationship in a nationally representative sample of US adults (National Health and Nutrition Examination Survey 2007-2012), which included thyroid test results and at least one blood pressure measurement (N = 8837). RESULTS: Sixty-five of these clinic patients had elevated blood pressure based on criteria suggested by the American College of Cardiology/American Heart Association. These patients had similar thyroid hormone levels as patients who did not have hypertension but tended to be older. Ordinary least squares regression analysis of the National Health and Nutrition Examination Survey 2007-2012 data demonstrated a significant positive association between free T3 levels and systolic blood pressure, adjusting for age, sex, and the use of levothyroxine. CONCLUSIONS: These findings from a specialty clinic and a national sample suggest that clinicians should consider the possibility of hyperthyroidism in patients with hypertension, even in older patients.

Plasma Membrane Na⁺-Coupled Citrate Transporter (SLC13A5) and Neonatal Epileptic Encephalopathy.

SLC13A5 is a Na⁺-coupled transporter for citrate that is expressed in the plasma membrane of specific cell types in the liver, testis, and brain. It is an electrogenic transporter with a Na⁺:citrate3- stoichiometry of 4:1. In humans, the Michaelis constant for SLC13A5 to transport citrate is ~600 µM, which is physiologically relevant given that the normal concentration of citrate in plasma is in the range of 150-200 µM. Li⁺ stimulates the transport function of human SLC13A5 at concentrations that are in the therapeutic range in patients on lithium therapy. Human SLC13A5 differs from rodent Slc13a5 in two important aspects: the affinity of the human transporter for citrate is ~30-fold less than that of the rodent transporter, thus making human SLC13A5 a low-affinity/high-capacity transporter and the rodent Slc13a5 a high-affinity/low-capacity transporter. In the liver, SLC13A5 is expressed exclusively in the sinusoidal membrane of the hepatocytes, where it plays a role in the uptake of circulating citrate from the sinusoidal blood for metabolic use. In the testis, the transporter is expressed only in spermatozoa, which is also only in the mid piece where mitochondria are located; the likely function of the transporter in spermatozoa is to mediate the uptake of citrate present at high levels in the seminal fluid for subsequent metabolism in the sperm mitochondria to generate biological energy, thereby supporting sperm motility. In the brain, the transporter is expressed mostly in neurons. As astrocytes secrete citrate into extracellular medium, the potential function of SLC13A5 in neurons is to mediate the uptake of circulating citrate and astrocyte-released citrate for subsequent metabolism. Slc13a5-knockout mice have been generated; these mice do not have any overt phenotype but are resistant to experimentally induced metabolic syndrome. Recently however, loss-of-function mutations in human SLC13A5 have been found to cause severe epilepsy and encephalopathy early in life. Interestingly, there is no evidence of epilepsy or encephalopathy in Slc13a5-knockout mice, underlining the significant differences in clinical consequences of the loss of function of this transporter between humans and mice. The markedly different biochemical features of human SLC13A5 and mouse Slc13a5 likely contribute to these differences between humans and mice with regard to the metabolic consequences of the transporter deficiency. The exact molecular mechanisms by which the functional deficiency of the citrate transporter causes epilepsy and impairs neuronal development and function remain to be elucidated, but available literature implicate both dysfunction of GABA (γ-aminobutyrate) signaling and hyperfunction of NMDA (N-methyl-d-aspartate) receptor signaling. Plausible synaptic mechanisms linking loss-of-function mutations in SLC13A5 to epilepsy are discussed.

Mechanisms of pain in aging and age-related conditions: Focus on caregivers.

Pain is a complex, subjective experience that can significantly impact quality of life, particularly in aging individuals, by adversely affecting physical and emotional well-being. Whereas acute pain usually serves a protective function, chronic pain is a persistent pathological condition that contributes to functional deficits, cognitive decline, and emotional disturbances in the elderly. Despite substantial progress that has been made in characterizing age-related changes in pain, complete mechanistic details of pain processing mechanisms in the aging patient remain unknown. Pain is particularly under-recognized and under-managed in the elderly, especially among patients with Alzheimer's disease (AD), Alzheimer's disease-related dementias (ADRD), and other age-related conditions. Furthermore, difficulties in assessing pain in patients with AD/ADRD and other age-related conditions may contribute to the familial caregiver burden. The purpose of this article is to discuss the mechanisms and risk factors for chronic pain development and persistence, with a particular focus on age-related changes. Our article also highlights the importance of caregivers working with aging chronic pain patients, and emphasizes the urgent need for increased legislative awareness and improved pain management in these populations to substantially alleviate caregiver burden.

Neuro-ophthalmic challenges and multi-morbidity in vasculitis among the older adults.

INTRODUCTION: Vasculitides are a heterogeneous group of disorders producing inflammation of blood vessels (e.g. arteries or veins). All major vasculitides potentially have ophthalmological symptoms and signs including visual loss. Co-morbidity, multimorbidity, polypharmacy, and geriatric syndromes all play important roles in patient outcomes for these rheumatic conditions in the elderly. This monograph reviews the NCBI PubMed database (Feb 2023) literature on the neuro-ophthalmic and geriatric considerations in vasculitis. AREAS COVERED: Cogan Syndrome, Granulomatosis with Polyangiitis, Giant Cell Arteritis, Polyarteritis Nodosa, Takayasu Arteritis, Vasculitis epidemiology, and neuro-ophthalmological symptoms. EXPERT OPINION: Geriatric patient care for vasculitis with neuro-ophthalmological manifestations can be complicated by the interplay of multiple co-morbidities, polypharmacy, and specific geriatric syndromes. The valuation and treatment of vasculitis and the complications associated with the disease can negatively impact patient care. Advances in noninvasive imaging and updates in diagnostic criteria have enabled increased identification of patients at earlier stages with less severe disease burden. Novel therapeutic agents can be glucocorticoid sparing and might reduce the adverse effects of chronic steroid use. Holistic care models like the 5 M geriatric care model (mind, mobility, medications, multicomplexity, and matters most) allow patients' needs to be in the forefront with biopsychosocial aspects of a patient being addressed.

The Spanish Flu of 1918: A Historical Reflection and Lessons from Masonic Lodges.

A catastrophic Spanish flu pandemic spread throughout the world during 1918-1919. In the spring of 1918, an army training center at the Fort Riley Kansas reported the first cases of Spanish flu in the United States. The first reported cases of the Spanish Flu of the virus in Kansas were quite moderate. The Spanish flu took an ominous turn in the fall of 1918 when injured soldiers who contracted the Spanish flu returned to the United States, spreading the illness across urban and rural communities. During this period of the Spanish flu, the freemason lodges served as accessory hospitals to help manage the growing Spanish flu cases across the United States. In this paper, we explore the experiences, challenges, and lessons from Freemason lodges during the Spanish flu to provide context and historical insights into the overlaps between the Spanish Flu and the current COVID-19 pandemic.

The Influence of Religious Affiliation and Attitudes of Clinical Genetic Testing Among Medical Students in the West Texas Region.

Background: Genetic counseling is an essential and pertinent field in any society to lower the prevalence of hereditary disorders. However, the desire to undergo counseling and genetic testing varies widely depending on the cultural background and level of scientific literacy of the individual. In this survey, we examine the perspectives of medical students on clinical genetic testing based upon their religious tradition. Methods: The total number of participants in the study was 257 (122 male and 135 female) second year medical students at Texas Tech University Health Sciences Center (TTUHSC). The distribution of religious identification (Atheist, Christian, Hindu, Jewish, Muslim, Spiritual/not Affiliated, and Other) among the second-year medical students. The survey was available to students through TTUHSC's Omnibus survey program for a period of two weeks. Results: Most of the second-year medical students interviewed identified as being Christian (67%) with the next highest religious identification being Spiritual/not Affiliated (9%), Atheist (8%), and Muslim (6%). With regards to genetic tests, most of the students (95%), regardless of religious identification, have not used any commercial genetic testing services. Most second year medical students regardless of religious affiliation had similar agreement with questions regarding clinical genetic testing. However, there was a similar drop in agreement when it came on where students would want genetic screening to be performed regularly in clinics/hospitals. Conclusion: Given the numerous factors that must be considered, such as the patient's attitudes, knowledge, and beliefs towards the counseling process and genetic testing, genetic counseling is a challenging problem. Each target population's history, relevant exposure to, and domain expertise must be considered while promoting decision-making in genetic testing.