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Multi-system Effects of Delayed Porphyria Diagnosis
No full textBackground: Acute Intermittent Porphyria is a life-threatening, debilitating, but treatable condition that often eludes diagnosis. Symptoms can manifest in a variety of ways, making it critical to consider in patients that present with multisystem dysfunction. While some symptoms can include psychiatric disruptions, an underlying organic cause should not be discounted.
Case Information: A 17-year-old female with history of abdominal pain presented to the hospital due to severe abdominal pain, requiring continuous opioid medications. She underwent cholecystectomy but continued to suffer. She experienced a seizure like event, decompensated into respiratory arrest requiring CPR. She recovered and discharged home a week later. She continued to experience pain, rapidly progressive numbness, weakness, and inability to walk. She was hospitalized again, noted to have dysarthria, multiple electrolyte abnormalities, and evidence of end-organ damage. Initially, she was diagnosed with Functional Neurological Disorder. She was transferred to a higher level of care, where she underwent extensive lab work, MRI Brain (negative), and EEG (negative). She was transferred to a dedicated pediatric hospital, where she was immediately diagnosed with porphyria. She had notable respiratory insufficiency with acidosis, requiring tracheostomy and gastrostomy placement. She began treatment with Hemin, slowly recovered completely, and is now back to a normal life.
Conclusions: Individuals with porphyria are at increased risk for significant long-term effects if the diagnosis is delayed or missed entirely. Porphyria needs to be considered when patients exhibit a combination of polyneuropathy, psychological disturbances, hematuria and abdominal pain
Exploring Anatomical Variations: A Case Study of an Aortic Arch and Left Superior Intercostal Artery Variants with Clinical Considerations
No full textBackground: In its usual pattern, the aortic arch has three branches, namely, from right to left, brachiocephalic trunk, left common carotid artery, and left subclavian artery. Normally, as one of the branches off the left subclavian artery, the costocervical trunk gives off the left superior intercostal artery. The aim of this case is to describe a variation in the aortic arch wherein the left common carotid artery branches from the brachiocephalic trunk, with an additional rare finding of the left superior intercostal artery branching directly from the left subclavian artery.
Case Information: As part of the cadaveric anatomy laboratory requirement of the Cardiopulmonary System Course (MEDE7615), our group performed a dissector-directed study of the thoracic cavity of a 67-year-old female donor to the UNTHSC Willed Body Program. Upon removal of the anterior part of the rib cage and subsequent exposure of the mediastinum and its contents, a variation in the branching pattern of the aortic arch in the superior mediastinum was dissected, cleaned, and identified. Following dissection of the aortic arch and its branches, we observed variations in the aortic arch and left superior intercostal artery. In this donor, the left common carotid artery branched from the brachiocephalic artery. This created only two vessels off the aortic arch rather than the three typically seen. We also observed that, on the left side, the superior intercostal artery branched directly from the subclavian artery and not from the costocervical trunk of the subclavian artery. This variant placed the left superior intercostal artery in a position more inferior and posterior in the upper part of the left pleural cavity.
Conclusion: Awareness of the aortic arch and left superior intercostal artery variations are clinically relevant to ensure prevention of potential surgical errors and ambiguity when viewing radiologic images
Risk of Overuse Injury and Burnout as Consequences of Early Specialization in Youth Sports
No full textPurpose: In the US, 60 million children participate in organized youth sports yearly and there is a growing emphasis on athletes specializing in a particular sport and developing their skill. Sports Specialization has been defined as participation in a single sport, which entails quitting all other sports, while also participating in year-round training (>8 months per year). The consequences of specializing in one sport at an early age including risks of overuse injuries, greater susceptibility to early burnout, and lack of social development. The purpose of the present study is to explore the literature related to youth sports specialization and its relationship to burnout and overuse injuries. Methods: A literature review was conducted using electronic databases, and the reference list of the relevant articles was screened for titles and abstracts containing the keywords. The keywords used included specialization, youth athletics, burnout, adolescence, children, organized sport, overtraining syndrome, awareness, prevention. The retrospective search was limited to: articles in English; studies in the US; articles including athletes in high school or younger; articles including overuse injury, burnout, specialization in the title or abstract. Based on above criteria, the search yielded 28 articles that included case studies, qualitative and quantitative studies, and systematic reviews. Results: Specializing in a single sport as well as participating in many hours per week training can lead to overuse injuries. Youth athletes who participated in more hours of training or specialized early were more likely to report history of injuries, particularly in lower extremities. Early sports specialization was associated with an increased risk of developing anterior knee-pain pathologies compared to their multi-sport counterparts. Compared to healthy athletes, injured athletes spent more hours per week in sports and there was an independent risk of injury and overuse injury in athletes specializing in a single sport. Burnout and dropout are positively correlated in youth athletes. Main factors contributing to sports dropout were lack of support from school friends, lack of support from teammates, and pressure from parents. Additionally, players that dropped out began their training at a younger age and participated in more hours per year training between ages 12-13. One study used an athlete burnout questionnaire and found that, compared to multi-sport athletes, specialized athletes reported higher levels of burnout, a reduced sense of accomplishment, sport devaluation, and exhaustion. Conclusion: These findings indicate that levels of specialization are related to psychological burnout and increased rate of overuse injuries in youth athletes, primarily through time spent in sports. Yet there is a further need for more research into whether multisport athletes are at a decreased risk of injury due to engagement in a broader set of movements and thus overall muscle strength and stability, or whether it is due to less hours spent overtraining one muscle group. Overall, educational programs should be developed to educate parents and coaches about risks of overtraining, early signs of overuse injuries, and positive ways to build a youth athlete’s confidence in their ability to play sports to avoid injury and burnout
Investigating the mechanism of action of metformin and tolfenamic acid in medulloblastoma cells
No full textPurpose: Medulloblastoma, a highly malignant CNS tumor primarily diagnosed in children, presents a complex challenge in the field of medicine. While current multimodal treatment approaches, including total excision, chemotherapy, and radiation, yield relatively high survival rates, they are often accompanied by a range of significant adverse effects in adulthood, including neurological and motor deficits, endocrine dysfunction, hearing loss, and secondary tumors. Thus, more recent studies have shifted their focus to developing alternative, more precisely targeted anti-tumor therapies to mitigate the toxicity associated with existing therapies and enhance patient quality of life. An approach to address this problem involves investigating the synergistic potential of drug combination therapy using FDA-approved drugs to treat medulloblastoma. Among the drugs being investigated are Metformin (Met), an antidiabetic medication, and Tolfenamic Acid (TA), a nonsteroidal anti-inflammatory drug (NSAID) used for migraine treatment. Both drugs have been shown to exhibit anti-cancer activity. Previous work conducted in our laboratory has provided evidence of TA’s anticancer activity being mediated through the downregulation of pro-cancer Sp1 and survivin protein expression. The objective of this study was to enhance understanding of the mechanisms of action of metformin and tolfenamic acid by assessing their cell cycle-associated effects on DAOY human medulloblastoma cancer cells using Western blotting and flow cytometry techniques. Methods: The efficacies of Met and TA in terms of their anticancer effects were evaluated by determining the IC50 values of each drug using CellTiter-Glo and CCK-8 cell viability assays. The cell cycle effects of TA and Met were studied by Western blot analysis using protein extracts from treated DAOY cells. In addition, a cell cycle analysis of treated cells was performed using flow cytometry. Results: In our studies, both TA and Met were found to demonstrate anti-proliferative effects on DAOY cells. As demonstrated by Western blotting and flow cytometry analysis, the antiproliferative effects of both TA and Met were mediated through cell cycle arrest. Conclusion: This study suggests the significant potential of utilizing Met and TA in novel drug combination therapy for medulloblastoma. Their effects on protein expression open possibilities for enhancing cell cycle arrest or inducing apoptosis while decreasing the use of toxic therapies. Given the importance of minimizing long-term effects in children being treated for medulloblastoma and enhancing their quality of life, the mechanisms of Tolfenamic Acid and Metformin can be further explored
Total Hip Arthroplasty Using the United Orthopedic Conformity Stem Femoral Hip System: A Review of Outcomes
No full textPurpose: Total hip arthroplasty (THA) is one of the most common and successful orthopedic procedures, markedly enhancing patient quality of life, reducing pain severity, and maximizing post-operative function. This study assesses the United Conformity Stem Femoral Hip System, distinguished by its standard and high offset options and the ability for precise adjustment to optimize joint stability and tension based on the surrounding soft tissue, with the goal of improving patient outcomes for THA.
Methods: A cohort of 415 patients, who underwent primary THA with the United Conformity Stem Femoral Hip System from November 2019 to November 2021, was retrospectively reviewed to evaluate the clinical effectiveness, safety, and survival over the first 2 years post-operation. The primary endpoints of our study were significant improvements in four patient-reported outcome measures (PROMs), including Hip Disability and Osteoarthritis Outcome Score-Joint Replacement (HOOS-JR), Lower Extremity Activity Scale (LEAS), Visual Analog Scale (VAS), and Harris Hip Score (HHS) at 24 months post-procedure when compared to preoperative scores. Secondary outcomes included implant survival and radiographic assessment for stability.
Results: Within the cohort, a total of 209 females and 66 males achieved a minimum of 2-year follow-up (66%). The mean age was 61.5 ± 9.9 years, with a mean BMI of 26.0 ± 5.4 kg/m2. At the 2-year follow-up, statistically significant improvements in HOOS-JR, LEAS, VAS, and HHS were observed compared to their baseline preoperative scores. Radiographic evaluations of the implants by two independent observers corroborated these PROMs findings. The cohort reported three revisions, one of which involved stem revision.
Conclusions: Our study affirms that the United Conformity Stem Femoral Hip System yields notable enhancements in functional capability and short-term radiographic stability in our evaluation of 2-year outcomes in primary THA, irrespective of surgical approach (anterior or posterior). These findings support the United Conformity Stem System’s capacity to meet the rising expectations of patients and surgeons alike, while providing excellent short-term outcomes
The Differential Effects of Type II Diabetes Between Ethnicities: A Descriptive Study Comparing Hispanics, African American, and Non-Hispanic White Older Adults with Type II Diabetes
No full textAbstract
Purpose: Type II diabetes mellitus (T2DM) is a significant risk factor for cognitive impairment. Individuals with T2DM have an increased risk for developing depression and depressive episodes. Additionally, T2DM worsens other comorbid conditions such as hypertension and high cholesterol. To gain a better understanding of the etiology and risk factors for the complications of T2DM, it is important to assess how T2DM impacts different ethnic groups. This study aims to explore how T2DM effects Hispanics (H), Non-Hispanic Whites (NHW), and African American (AA) older adults regarding self-reported health and past medical history, objective measures, and clinical blood work.
Methods: Data was collected from 767 (187 AA, 161 NHW, 419 H) participants with T2DM from the Health and Aging Brain Study: Health Disparities, baseline studies. T2DM was defined as an HbA1C of greater than or equal to 6.5 or by self-report. The participants had an average age of 65 years. One-way ANOVAS were run to examine group differences in demographics, physical activity (RAPA), affect (Geriatric Depression Scale: depression; Penn State Worry Questionnaire: worry), blood pressure, and clinical blood work.
Results: ANOVAs demonstrated significant differences in education between H (M = 8.84, SD = 4.51), NHW (M = 15.32, SD = 2.62), AA (M = 14.57, SD = 2.66) groups (F = 246.74, p <0.001). Significant differences in income were also recorded between H (M= 30,530.31, SD = 28,055.79), NHW (M =65,265.45, SD = 53,241.75), AA (M = 61,423.46, SD = 69,393.76) groups (F = 44.63, p < 0.001). Clinically, significant differences in systolic blood pressure were found between H (M = 140.83, SD = 20.98), NHW (M = 137.58, SD = 18.69), AA (M = 136.44, SD = 20.56) groups (F = 3.52, p = 0.03). The cholesterols (total cholesterol, HDL, triglycerides, LDL, HDL ratios, and non-HDL) were all statistically significant between groups (F range 3.35 – 21.13, p range <0.001 – 0.036). ANOVAs also highlighted significant differences in physical activity (RAPA) between H (M = 3.84, SD = 1.49), NHW (M = 4.18, SD = 1.52), AA (M = 4.18, SD = 1.62) groups (F = 4.61, p = 0.01). Lastly, significant differences in affect (GDS) were found between H (M = 7.73, SD = 6.72), NHW (M = 5.84, SD = 6.02), AA (M = 6.81, SD = 5.76) groups (F = 5.42, p = 0.01).
Conclusion: This study demonstrates that Hispanic older adults with T2DM exhibit a greater decline in overall health and wellness compared to their AA and NHW counterparts. Future research should compare type II diabetic Hispanics with non-diabetic Hispanics to determine if Hispanics are already at a baseline risk for potential health complications.National Institute on Aging (NIA) Grant
Factors associated with the acceptability of Lopinavir/Ritonavir formulations among children living with HIV/AIDS attending care and treatment clinics in Mbeya and Mwanza, Tanzania
No full textResearch Appreciation Day Award Winner - School of Public Health, 2024 Community Engaged Research AwardFACTORS ASSOCIATED WITH THE ACCEPTABILITY OF LOPINAVIR/RITONAVIR FORMULATIONS AMONG CHILDREN LIVING WITH HIV/AIDS ATTENDING CARE AND TREATMENT CLINICS IN MBEYA AND MWANZA, TANZANIA
Authors:
Jiwa NA[1],*, Ketang’enyi E1, Nganyanyuka K1, Mbwanji R1, Mwenisongole D1, Masuka E1, Brown M1, Charles M1, Mwasomola DL2 , Nyangalima T[2], Olomi W[3], Komba L1, Gwimile J1, Kasambala B1 and Mwita L1
*Corresponding author:
Email addresses: [email protected] [[email protected]] (Nadiya Alnoor Jiwa- PI and Pharmacist) and [email protected] [[email protected]] (Dr Lumumba Mwita- Author and Executive Director).
URL: https://www.texaschildrensglobalhealth.org/tanzania [https://www.texaschildrensglobalhealth.org/tanzania] and https://baylortanzania.or.tz/ [https://baylortanzania.or.tz/]
[1] Baylor College of Medicine Children’s Foundation, Tanzania.
[2] Mbeya Zonal Referral Hospital (MZRH)
[3] National Institute of Medical Research (NIMR)- Mbeya Medical Research Center (MMRC)
ABSTRACT
INTRODUCTION
Children living with chronic illnesses are offered formulations based on manufacturer and distributor research. The aim of this study is to better understand the perspectives of children and their caregivers in accepting Lopinavir/ritonavir (LPV/r) formulations.
METHODS
362 participants were recruited from two pediatric HIV/AIDS clinics in Mbeya and Mwanza, Tanzania, from December 2021 to May 2022. A translated questionnaire was piloted and validated at both clinics, followed by the implementation of a cross-sectional study.
RESULTS
169 participants (47.1%) reported general difficulties in swallowing, regardless of formulation, while 34.3% and 38.5% reported vomiting tablets and syrups, respectively. Statistical significance is shown to support that children can swallow medications if they can eat stiffened porridge (Ugali). This correlated with the lower incidence of younger children being able to swallow compared to older children (above six years of age). Children older than six years preferred taking tablets (independent of daily dosage) better than other formulations. Significantly, older children who attend school were associated with high odds of swallowing medicine (AOR = 3.06, 95%CI; 1.32–7.05); however, age was not found to be statistically related to ease of administration for Lopinavir/Ritonavir in this study.
CONCLUSIONS
Lopinavir/Ritonavir tablets remain the most accepted formulation among children and adolescents with HIV/AIDS. This study highlights the impact of various factors affecting the acceptability of pediatric formulation, suggesting that children younger than six years, unable to eat Ugali and not attending schools may be most vulnerable regarding their ability to accept Lopinavir/Ritonavir formulations. Further studies are needed to assess the acceptability of other medications in chronically ill children.
Paper published on January 2nd, 2024 and available on: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0292424 [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0292424]
Acknowledgement: Am grateful to Dr Scott Walters in his immense support for me to continue propagating this research from my previous work in my home, Tanzania
Nadiya Alnoor Jiwa, Eunice Ketang’enyi, Kapongola Nganyanyuka, Ruth Mbwanji, Danistan Mwenisongole, Eutropia Masuka, Mary Brown, Mary Charles, Davance Leonard Mwasomola, Thomas Nyangalima, Willyhelmina Olomi, Lilian Komba, Judith Gwimile, Bertha Kasambala, Lumumba Mwita
Published: January 2, 2024
https://doi.org/10.1371/journal.pone.0292424 [https://doi.org/10.1371/journal.pone.0292424
Using the Socioecological Model to Explain Disparities in Pain Management Between Hispanic and White Adults: A Literature Review
No full textPurpose: There is a longstanding history of racial disparities in pain management in the United States. Previous research has highlighted a trend in which Black and Hispanic patients are disproportionately at risk of experiencing inadequate pain treatment. For instance, studies have established that they are less likely to be prescribed analgesia and opioids compared to their White counterparts. Despite this knowledge, the underlying factors contributing to these disparities remain largely unexplored, particularly those concerning the Hispanic adult population. The purpose of this literature review is to utilize the socioecological model to explore patient, provider, and societal factors contributing to disparities in pain management between White and Hispanic adults.
Methods: The literature review was conducted on PubMed. A combination of key terms was used to search for articles discussing disparities in pain management between Hispanic and White adults. Articles were included in the review if they were written in English, based in the United States, published in 2013 or later, and utilized one or many keywords in the title or abstract. Furthermore, only quantitative and qualitative studies, systematic reviews, and narrative reviews were considered. Using these criteria, a total of 18 articles were selected for review.
Results: The results of this literature review support the notion that socio-ecological factors interact with one another and collectively contribute to disparities in pain management. At the patient level, differences in coping styles, underreporting pain, and perceived racial discrimination influence Hispanic patients' decision to seek pain management care from healthcare providers. At the provider level, bias and discrimination against Hispanic patients regarding pain treatment, along with language barriers, contribute to unequal healthcare practices. Finally, at the societal level, social and economic barriers impact Hispanic patients' ability to access and afford pain management care.
Conclusion: This literature review aimed to identify patient, provider, and societal level factors that contribute to disparities in pain care between Hispanic and White adults in the US. Understanding the unique challenges the Hispanic adult population face is crucial for developing targeted interventions and improving equitable access to pain management services. Therefore, healthcare providers should strive to identify and mitigate as many of these factors as possible to alleviate disparities in pain management and deliver equitable care
ADAM19 and ADAMTS4 expression in Human Optic Nerve Head Astrocytes
No full textPurpose: Glaucoma is characterized by the degeneration and death of retinal ganglion cells and their axons causing irreversible blindness. Various risk factors contribute to glaucoma onset, including intraocular pressure (IOP), age, and family history. In glaucoma, the primary site of damage is the optic nerve head (ONH). ONH astrocytes, a major cell type in the LC, are believed to play a significant role in the pathological remodeling of extracellular matrix (ECM) during glaucoma. Glaucoma patients have increased levels of transforming growth factor beta 2 (TGFβ2) in their aqueous humor, trabecular meshwork and ONH. TGFβ2 is a profibrotic cytokine known to induce the synthesis and deposition of ECM. Previously, we performed RNA sequencing of ONH astrocytes in which disintegrin and metalloproteinases (ADAMs) and ADAM with thrombospondin motifs (ADAMTS) were significantly dysregulated with TGFβ2 treatment compared to controls. ADAMs and ADAMTS4 influence cell phenotype by affecting cell adhesion, migration, proteolysis, and signaling pathways. The purpose of the present study was to determine a) if ONH astrocytes express ADAM19 and ADAMTS4 in ONH astrocytes and b) determine if TGFβ2 regulates ADAM19 and ADAMTS4 expression in ONH astrocytes.
Methods: Primary human ONH astrocyte cell strains (n=3) were treated with TGFβ2 (5ng/ml) or with a vehicle control for 48 hours. The effects of TGFβ2 on ADAM19 and ADAMTS4 were determined by qPCR and western blots using primary human ONH astrocyte cell cultures.
Results: ADAM19 and ADAMTS4 were expressed in ONH astrocytes. Treatment with TGFβ2 significantly increased mRNA levels of ADAM19 and ADAMTS4. However, western blot analysis showed no significant change in ADAM19 protein expression compared to control, while ADAMTS4 was increased with TGFβ2 compared to control.
Conclusions: TGFβ2 modulated the expression of ADAM19 and ADAMTS4 in ONH astrocytes. ADAM19 and ADAMTS4 may contribute to the pathogenic remodeling of the ONH in glaucoma. While further studies are needed, this research aims to shed light on the intricate mechanisms underlying glaucoma pathogenesis
First-in-class Peptide Molecules Targeting the MIEN1 Cancer signaling Pathway for which no inhibitors are currently identified
No full textResearch Appreciation Day Award Winner - School of Biomedical Sciences, 2024 Postdoctoral Oral Presentation AwardMigration and invasion enhancer 1 (MIEN1) overexpression characterizes several cancers and facilitates cancer cell migration and invasion. Leveraging conserved ITAM and prenylation motifs within MIEN1, we identified potent anti-cancer peptides. Among them, bioactive peptides LA3IK and RP-7 induced pronounced transcriptomic and protein expression changes at sub-IC50 concentrations. The peptides effectively inhibited genes and proteins driving cancer cell migration, invasion, and EMT pathways, concurrently suppressing EGF-induced NF-kB nuclear translocation in metastatic breast cancer cells. Specifically, peptides targeted the same signal transduction pathway initiated by MIEN1. Molecular docking and circular dichroism spectroscopy indicated the formation of MIEN1-peptide complexes. The third-positioned isoleucine in LA3IK and CVIL motif in RP-7 were crucial for inhibiting breast cancer cell migration. This is evident from the limited migration inhibition observed when MDA-MB-231 cells were treated with scrambled peptides LA3IK SCR and RP-7 SCR. Additionally, LA3IK and RP-7 effectively suppressed tumor growth in an orthotopic breast cancer model. Notably, mice tolerated high peptide doses of up to 90 mg/Kg well, surpassing significantly lower doses of 5 mg/Kg intravenously (iv) and 30 mg/Kg intraperitoneally (ip) used in both in vivo pharmacokinetic studies and orthotopic mouse model assays. D-isomers of LA3IK and RP-7 showed enhanced anti-cancer activity compared to their L-isomers. D-LA3IK remained stable in mouse plasma for 24 h with 75% remaining, exhibiting superior pharmacokinetic properties over D/L-RP-7. In summary, our findings mark the first report of short peptides based on MIEN1 protein sequence capable of inhibiting cancer signaling pathways, effectively impeding cancer progression both in vitro and in vivo.This work was supported by awards from the National Institute of Health under awards R01CA220273, U54MD006882 ,S21MD012472 and Summerfield G. Roberts foundation grant to Dr. Jamboor K. Vishwanatha