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Characterization of a potentially new therapeutic gel for Candida albicans treatment
No full textCandida albicans is a dimorphic fungus that is found in many parts of the human body, such as the mouth, throat, and gut, and is the most common cause of fungal infection in humans. While this fungus can exist without causing harm, under certain conditions, it can lead to infection, especially in wounds. Due to a current rise in antifungal resistance throughout the world, research on C. albicans is necessary for the development of new antifungal treatments. To aid in this effort, an antimicrobial gel (AMG) was formulated as a topical gel originally created for pain relief for shingles. Our research has found that AMG also exhibits antifungal properties that can interrupt the yeast-hyphal transition of C. albicans. This research aims to decipher the ability of AMG to inhibit or kill the growth of C. albicans. Through experimentation with four types of Candida (yeast form, hyphal form, wild type, and C. glabrata), inhibition can be demonstrated in both planktonic and biofilm growth. Additionally, it was found that AMG can restrict morphology, or in other words, lock C. albicans into the yeast form, which is the less aggressive and commensal form and not associated with infection like the hyphal form. This would allow the fungus to be avirulent and easier to treat or manage. AMG, in all, has shown to have potential as a new topical therapeutic option for Candida infections
Decreased NADPH levels may impair C. elegans mitochondrial function during aging
No full textWith aging there is increased hydrogen peroxide (H2O2) release from mitochondria causing oxidative damage. H2O2 detoxification systems include catalase as well as the peroxiredoxin and glutathione systems that both require NADPH, with parallel systems for each operating in the cytoplasm and mitochondria. For detoxification, H2O2 is converted to water by peroxiredoxins (PRDXs) or glutathione peroxidases (GPXs). During this process glutathione, PRDX, and thioredoxin become oxidized, and glutathione reductase (GSR) or thioredoxin reductase (TRXR) oxidize NADPH to NADP+ to reduce the antioxidants back to their active forms. The NADP+ must then be recycled back to NADPH by one of several enzymes including cytoplasmic glucose-6-phosphate dehydrogenase (G6PD) or 6-phosphogluconate dehydrogenase (PGD) or mitochondrial malic enzyme 3 (ME3) or isocitrate dehydrogenase (IDH2). NADP+ is generated from NAD+ by two NAD kinase (NADK) genes. NADPH levels decline with aging, but whether this contributes to the rate of aging is not yet known. Here, we use the nematode C. elegans to decrease NADPH levels to model aging and subsequently measure H2O2 levels and the oxygen consumption rate (OCR), a measure of mitochondrial function that declines with age. C. elegans genes nadk-1, nadk-2, gspd-1 (G6PD), T25B9.9 (PGD), men-1 (ME3) and idh-2 were individually knocked down to decrease NADPH levels. We also measured H2O2 and mitochondrial function in C. elegans trxr-1, trxr-2, prdx-2, prdx-3, and gsr-1 antioxidant mutants with and without decreasing NADPH levels. While decreasing NADPH levels in wild-type worms increased H2O2 as expected, decreasing NADPH levels in some antioxidant mutants unexpectedly decreased H2O2, suggesting the activation of a transcriptional stress response. So, mutants for antioxidant stress response transcription factors skn-1 (Nrf2), daf-16 (FOXO), or hsf-1 were used to determine the mechanism. The results from these experiments will aid in the understanding of the roles of NADPH and H2O2 in human aging and aging-related diseases
Xanomeline, a novel cholinergic antipsychotic drug, shows dose dependent effects of rodent EEG
No full textSchizophrenia is a debilitating disorder of the mind, affecting nearly 1% of the worldwide population. Affected individuals experience reality in a highly distorted fashion. Symptoms can include delusions, hallucinations, disorganized speech, trouble with thinking and a profound lack of motivation to engage in social activities. For nearly seventy-five years, the standard of care has not evolved much in this area and involved the use of dopaminergic antagonists that are only partially effective at best. Principally, these dopaminergic D2 antagonists combatted the so called “positive symptoms” like hallucinations and delusions. Other symptoms were largely unaffected. Recently, there was a paradigmatic change in that, for the first time, the Federal Drugs Administration (FDA) has approved a new drug, a cholinergic agonist at the M1 and M4 receptors as a new treatment for this troubling condition. While this drug appears to be effective against positive and negative symptoms like social withdrawal upon use over many weeks, the brain-wide changes in neural network activity after acute use is not well understood. Knowing that it has an immediate effect on brain networks would be a good biomarker that can allow us to construct hypotheses to better understand its locus of action within the brain. As a first step, we tested quantitative electroencephalographic (EEG) changes in rodents implanted with chronic epidural electrodes. We hypothesized that xanomeline would increase the activity of the prefrontal cortex, reflected as a reduction in slow wave (0.5-9 Hz) activity and an increase in high frequency gamma (30-100 Hz) band activity. As hypothesized, we saw robust reductions (P\u3c0.005; two way-ANOVA with treatment and frequency as factors) in slow wave activity while gamma relative power (as a fraction of the total power) increased significantly. We conclude that quantitative EEG is a viable biomarker approach to monitor the brain activity of the latest antipsychotic drug, xanomeline. Our finding lay the groundwork for future translational studies in clinical subjects
Rural-Urban Disparities in Telehealth Services Provision Post Covid-19 Pandemic in South Carolina and Alabama.
No full textThe COVID-19 pandemic accelerated the adoption of telehealth services across the US, particularly in rural areas where access to healthcare is often constrained by distance, income, internet access, and time. This study investigates the variation in telehealth services between urban and rural health department (HD) and federally qualified health center (FQHC) clinics in Alabama (AL) and South Carolina (SC) from 2019 to 2022. The objective is to assess disparities in telehealth adoption, modalities, and sustainability disparities before and after the COVID-19 pandemic. Using survey data from HD and FQHC clinics in SC and AL on telehealth services, chi-square tests, and difference-in-differences (DiD) analysis were conducted. The DiD approach, utilizing generalized estimating equations and modified Poisson regression, assessed changes in telehealth service provision between rural and urban clinics over time. The analysis compared telehealth service provision and modalities in 2019 (pre-COVID) and 2022 (post-COVID), along with continued plans for telehealth provision. Findings indicate an overall increase in telehealth services from 2019 to 2022, with urban adopting telehealth more than rural areas (DiD: -16.8%, P=0.037). Primary healthcare services saw a greater increase in urban than in rural clinics (DiD: -20.8%, p=0.005). Mental/behavioral health services also increased, but at a slower rate in rural clinics compared to urban (DiD: -15.9%, p=0.023). While a combination of phone and video calls is the most common (53.3% in urban, 34.3% in rural), phone-only use was significantly higher in rural areas (41.1%) than in urban areas (21.5% p=0.027). Although most clinics plan to continue offering telehealth services, more rural clinics will offer limited services (36.0% urban; 41.6% rural) in the future. These findings highlight that, while telehealth expanded post-pandemic, urban clinics benefited more. Expanding telehealth infrastructure and addressing gaps in rural areas are essential for ensuring equitable healthcare access, particularly for reproductive and mental health services
Cervical Cancer Process Improvement
No full textBackground. Although preventable, cervical cancer (CC) still presents significant burden for women in the United States, particularly those belonging to marginalized groups. Federally Qualified Health Centers (FQHCs) play a crucial role in providing cervical cancer screening (CCS) to these individuals but often have suboptimal CCS rates. Purpose. The purpose of this quality improvement project is to improve the CCS process for an FQHC. Aims. By addressing identified process gaps, this project aims to increase CCS rates by implementing a formal screening process. Methods. A clinic provider meeting was held to educate PCPs on CCS guidelines and use of a process improvement. An alert was added to the electronic health record (HER) of each patient due for CCS. Education handouts are being provided to women of CCS age outlining what CC is, disease significance, risk factors, how to obtain screening, and prompts patients to talk to their PCP about CCS. Outcome Measures. The number of patient education handouts given, number of patients offered same day CCS or WH referral, number of same day screenings or referrals completed, number of patients who decline screening, and if an increase in CCS compliance has occurred at project completion will be measured. Findings. Although project implementation is still occurring, it has yielded some preliminary findings and limitations. There has been good utilization of the provider checklist, but they are often incomplete. Also, many patients report having had screening elsewhere. Without results, however, compliance cannot be confirmed. Lastly, this clinic will be changing EHRs during project implementation, resulting in the need to add the EHR prompt to the new system
Impact of Non-Alcoholic Fatty Liver Disease Severity on Coronary Artery Disease Progression: A Retrospective Cohort Study
No full textIntroduction Non-alcoholic fatty liver disease (NAFLD) is a known cardiometabolic risk factor, yet its impact on coronary artery disease (CAD) progression remains uncertain. Hepatic fibrosis in NAFLD may contribute to accelerated atherosclerosis via systemic inflammation, insulin resistance, and endothelial dysfunction. This study evaluates the association between NAFLD severity and CAD progression, focusing on liver fibrosis as a potential predictor of cardiovascular risk. Methods A retrospective cohort study was conducted from the Nationwide Inpatient Sample database on patients with NAFLD and CAD who underwent serial coronary imaging (angiography or coronary calcium scoring) between 2015–2023. NAFLD severity was categorized using the Fibrosis-4 Index (Fib-4): mild (\u3c1.3), moderate (1.3–2.67), and severe (\u3e2.67). Primary outcomes included CAD progression (≥20% stenosis increase or new obstructive lesion \u3e70%) and major adverse cardiac events (MACE: myocardial infarction, stroke, or cardiovascular death). Statistical analysis included multivariate logistic regression adjusted for age, diabetes, hypertension, dyslipidemia, BMI, and statin use. Results A total of 1,275 patients (mean age 62.4 ± 9.8 years, 54.2% male) were analyzed. CAD progression was observed in 15.2% of mild, 29.7% of moderate, and 48.4% of severe NAFLD patients (p\u3c0.001). After adjustment for confounders, severe NAFLD was associated with a 2.6-fold higher risk of CAD progression (OR 2.61, 95% CI 1.89–3.45, p\u3c0.001). MACE incidence was highest in the severe NAFLD group (21.5%) compared to moderate (12.3%) and mild (5.7%) (p=0.003). Fib-4 \u3e2.67 and liver stiffness \u3e10 kPa were independent predictors of CAD progression and MACE. Conclusion NAFLD severity, particularly advanced fibrosis, is strongly associated with CAD progression and increased cardiovascular events. These findings highlight the need for incorporating liver fibrosis assessment into cardiovascular risk stratification models to improve early intervention and patient outcomes
What’s my name? P300 event-related potential responses to participant’s own name versus a nickname
No full textThe P300 is a brainwave that is often associated with attention allocation. Previous research has demonstrated that the P300 is sensitive to self-relevance. Meaning, a participant elicits a large P300 when presented with autobiographical information, such as their own name. This effect has been extended to include other types of self-relevant presentations, including personal belongings. This suggests that our brain’s self-relevant attentional bias may be broader than what has been previously speculated. So, what makes something “self-relevant”? Does it have to do with emotion, or is it simply a matter of familiarity? To investigate this question, we measured P300s in response to the participant’s own name, and an animal name. The participant was then told that animal name would be their nickname for the study, and the P300 was measured again. For each of 6 days following the completion of the study, the participant filled out a survey stating their assigned nickname. On the 7th day, the participant returned to the lab and P300s from their own name and the nickname were measured again. We then administered a survey to find out how participants felt about their own name (example item: “I like my name.”). We expect to find that the P300 elicited by the participant’s nickname increases over time as they become more familiar with it. However, it likely will not become as robust as their actual name. Given the broad range of stimuli used in self-relevant experiments, we do not expect participant sentiment towards one’s name to correlate with their self-name P300. The current study will inform studies of self-relevance by helping to clarify the neural origins of self-referential processing
Using Borderline Hypertensive Rats to Study How Post-Traumatic Stress Syndrome Augments the Cardiogenic Sympathetic Afferent Reflex
No full textPost Traumatic Stress Disorder (PTSD) is a condition where individuals encounter extreme thoughts or feelings after a traumatic event. This can lead to flashbacks that can significantly impact their physical and mental well-being. PTSD can also increase sympathetic nervous system activity leading to hypertension and increased risk of myocardial ischemia. Increased sympathetic activity can also augment the severity of the cardiogenic sympathetic afferent reflex (CSAR), in which myocardial ischemia activates cardiac nerve endings and increases coronary blood flow. Paradoxically, it also increases the heart\u27s oxygen demand and may expand the locus of ischemic injury. Thus, PTSD not only increases the chances of myocardial ischemia but may also increase mortality. However, the effect of PTSD on this reflex has been largely overlooked. We have recently shown that in Sprague Dawley rats, chronic foot shock stress modeling PTSD augments the CSAR. We also showed that the CSAR is elevated in the spontaneous hypertensive rat, a model of sympathetically mediated hypertension. In this study, we generated a Borderline Hypertensive Rats (BHR) colony. These rats exhibit mildly elevated blood pressure under baseline conditions but experience a sharp, sustained increase when exposed to stress. We exposed BHRs to foot shock stress twice daily for two hours for fifteen consecutive days. After treatment, we measured blood pressure, heart rate, and sympathetic nerve activity and tested the CSAR. We hypothesized that BHRs exposed to chronic stress would show increased blood pressure and heart rate and augmented CSAR compared with unstressed BHRs. Strangely, blood pressure, heart rate, sympathetic nerve activity, or CSAR response in BHRs exposed to chronic stress was no different compared with unstressed BHRs. Our next step is to outfit rats with radiotelemetry devices to measure daily blood pressure and heart rate and increase the intensity of the foot-shock stress to ensure it elicits hypertension
Long COVID and Post-Covid Conditions (PCC) in 2025
No full textThe COVID/SARS-2 pandemic left a lasting impact on healthcare perspectives and the management of chronic illnesses. It has been seen that COVID leaves individuals with a myriad of health issues after infection, an illness known as Long COVID or Post-COVID Conditions (PCC). Long COVID is defined by signs and symptoms that develop four or more weeks after infection. Research suggests three scenarios: (1) Persistent, signs and symptoms that last for weeks, months and years after initial infection, (2) Recurrent, symptoms that come and go, and (3) New, meaning signs and symptoms that were not present in the initial phase of infection. People who experience these various symptoms are known as Covid “long haulers” There is a considerable volume of studies being conducted on Long COVID. A literature review of peer reviewed journal articles from 2021 to the present was done encompassing the fields of cardiopulmonary medicine, dermatology, neurology, and rheumatology. These fields were selected based on high prevalence of signs and symptoms in each respective specialty. Risk factors of Long COVID include severe COVID-19 infection requiring hospitalizations, comorbidities such as diabetes mellitus, asthma, or obesity, and lack of prior vaccination for COVID-19. Articles that stratified the symptoms on the basis of severity found that symptom severity correlated with illness severity. The most common long COVID cardiopulmonary manifestations include arrhythmias, chest pain, and shortness of breath. Dermatological manifestations include chronic urticaria, telogen effluvium (diffuse transient hair loss), chilblains (“COVID toes”), and flare-ups of other common skin conditions such as psoriasis, eczema, seborrheic dermatitis. Neurologic manifestations consist of issues with concentration and memory loss (“brain fog”), sleep disturbances, headaches, dizziness, tremors, anxiety and depression. Rheumatological symptoms comprised of generalized weakness, chronic fatigue, persistent joint pain and swelling, and myalgia. Knowledge of long-term Post-COVID Conditions (PCC) is essential in assessing COVID “long haulers”
Enhancing Anti-fungal Therapy: Evaluating Clove Oil vs. Alternative Oils in Nystatin Formulations
No full textBackground: Candida albicans infections present a significant challenge due to increasing antifungal resistance, necessitating more effective treatment strategies. This study explores clove oil as an enhancer for nystatin, a polyene antifungal, and compares its efficacy to oleic acid and Kollicream IPM, two commonly used excipients. Our previous research demonstrated synergism between clove oil and nystatin; this study further evaluates whether clove oil offers superior antifungal activity than other oils and its potential to combat resistance-related treatment failures. Methods: A 7.73% clove oil and 2.27% nystatin formulation was tested against C. albicans, alongside equivalent oleic acid and Kollicream IPM formulations. The intrinsic antifungal properties of each oil were also assessed. Agar diffusion assays were performed using C. albicans inoculated in Sabouraud Dextrose Broth. Wells (5 mm) were aseptically punched into agar plates, and each formulation was introduced. Plates were incubated at 31°C with 5.0% CO₂ for 7 days. Zones of inhibition were measured after 5 days to determine antifungal efficacy. Results: A solution containing 7.73% clove oil and 2.27% nystatin exhibited an inhibition zone of 2.9 cm. A mixture of 7.73% oleic acid and 2.27% nystatin showed an inhibition zone of 1.9 cm, while the combination of 7.73% Kollicream IPM and 2.27% nystatin resulted in an inhibition zone of 2.5 cm. When tested independently, only clove oil demonstrated inhibitory effects (zone of inhibition of 3.4 cm), while oleic acid and Kollicream IPM did not exhibit any inhibition. Discussion: Among the tested oils, clove oil was the only one to exhibit independent antifungal effects against C. albicans. Furthermore, when combined with nystatin, clove oil significantly enhanced the drug’s fungicidal activity compared to oleic acid and Kollicream IPM, reinforcing its potential as a valuable excipient for optimizing antifungal formulations