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Evaluating the efficacy of wireless near infrared spectroscopy sensors for detecting central hypovolemia during simulated hemorrhage in humans
No full textResearch Appreciation Day Award Winner - Texas College of Osteopathic Medicine, 2024 Student Research Award - 2nd PlaceBackground: Early identification of blood loss is essential to decrease mortality from hemorrhage, a major cause of death in the military and civilian trauma settings. An industry partner has created noninvasive and wireless near infrared spectroscopy (NIRS) sensors to measure somatic tissue oxygenation (StO₂) for early detection of blood loss. In this study, we investigated the efficacy of these sensors for tracking the reduction in central blood volume (indexed by stroke volume) in humans undergoing simulated hemorrhage. We hypothesized that each NIRS sensor will progressively track the reduction in central blood volume during simulated hemorrhage in humans.
Methods: Eight healthy humans (3 F, 5M; 25.3 ± 2.0 y) participated in a simulated hemorrhage protocol induced via application of lower body negative pressure (LBNP) to presyncope. Following baseline, the LBNP chamber pressure was decreased every 5-min to -15, -30, -45, -60, -70, -80, -90 and -100 mmHg, or until the onset of presyncopal symptoms (defined as a systolic arterial pressure <80 mmHg or subjective symptoms). Heart rate (via lead II ECG) and arterial pressure (via finger photoplethysmography) were monitored continuously. Stroke volume was estimated from pulse contour analysis of the finger photoplethysmography waveform. A total of five NIRS sensors measured StO2 at different anatomical locations including the sternum, forearm, deltoid, thigh, and calf. Data were analyzed over the final 3-min of each LBNP stage and the 1-min immediately prior to the onset of presyncope. Correlations between the relative changes in StO₂ of each sensor and stroke volume were assessed.
Results: Stroke volume decreased by 46.9± 16.3 % at presyncope. StO₂ decreased by 1.5 ± 7.8 % at the sternum, 9.6 ± 7.4 % at the forearm, 1.5 ± 3.6 % at the deltoid, 21.3 ± 15.8 % at the thigh, and 30.4 ± 27.5 % at the calf. Of all the sites, the strongest relationship between decreases in StO₂ and stroke volume was at the calf (R-value range: 0.70-0.99, R-value mean: 0.89 ± 0.11). The sensors located at each of the other sites tracked stroke volume with high inter-participant variability (sternum, R-value range: -0.71-0.99, R-value mean: 0.24 ± 0.79; forearm, R-value range: -0.09-0.99, R-value mean: 0.61 ± 0.40; deltoid, R-value range: -0.97-0.96, R-value mean: 0.26 ± 0.83; thigh, R-value range: -0.75-0.99; R-value mean: 0.68 ± 0.64).
Conclusion: Unexpectedly, the NIRS sensor on the calf, which was inside the LBNP chamber, performed the best out of the five sites in tracking the progressive reduction in central blood volume in healthy human participants. This may be due to the pooling of blood volume in the lower limbs with the LBNP stimulus, which increased deoxygenated hemoglobin, resulting in an overall lower measurement of tissue oxygen saturation. This finding is interesting, and further modifications and testing of these sensors are required to reliably track blood volume loss in patient populations.Department of Defense (W911QY22P0135
Impact of sex and hypoxia on brain region-specific expression of membrane androgen receptor AR45 in rats
Get PDFBACKGROUND: Sex differences in oxidative stress-associated cognitive decline are influenced by sex hormone levels. Notably, oxidative stress-associated neuronal cell death can be exacerbated through testosterone signaling via membrane androgen receptor AR45, which is complexed with G protein G(alphaq) within plasma membrane-associated lipid rafts. The objective of this study was to elucidate the impact of sex on the expression of AR45 and G(alphaq) in brain regions associated with cognitive function, specifically hippocampus subregions and entorhinal cortex. Additionally, we investigated whether chronic intermittent hypoxia (CIH), an oxidative stressor with sex-specific effects, would modulate AR45 and G(alphaq) expression in these brain regions. METHODS: Adult male and female Sprague-Dawley rats were exposed to CIH or normoxia (room air) during their sleep phase for 14 days. We quantified AR45 and G(alphaq) protein expression in various cognition-associated brain regions [dorsal hippocampal CA1, CA3, dentate gyrus (DG), and entorhinal cortex (ETC)] via western blotting. For comparisons, AR45 and G(alphaq) protein expression were also assessed in brain regions outside the hippocampal-ETC circuit [thalamus (TH) and striatum (STR)]. RESULTS: The highest AR45 levels were expressed in the hippocampal CA1 and DG while the lowest expression was observed in the extrahippocampal STR. The highest G(alphaq) levels were expressed in the hippocampal-associated ETC while the lowest expression was observed in the extrahippocampal TH. Females expressed higher levels of AR45 in the hippocampal DG compared to males, while no sex differences in G(alphaq) expression were observed regardless of brain region assessed. Moreover, there was no effect of CIH on AR45 or G(alphaq) expression in any of the brain regions examined. AR45 expression was positively correlated with G(alphaq) expression in the CA1, DG, ETC, TH, and STR in a sex-dependent manner. CONCLUSION: Our findings reveal enrichment of AR45 and G(alphaq) protein expression within the hippocampal-ETC circuit, which is vulnerable to oxidative stress and neurodegeneration during cognitive decline. Nonetheless, CIH does not modulate the expression of AR45 or G(alphaq). Importantly, there are sex differences in AR45 expression and its association with G(alphaq) expression in various brain regions, which may underlie sex-specific differences in cognitive and motor function-associated declines with aging.The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by NIH R01 NS0091359 and UNTHSC Seed grant funding to RC, AHA 22POST-903250 to JB, AHA 22PRE-900431 to JG, and NIH T32 AG020494 to SM. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health
Recurrence and progression of Wolff-Parkinson-White syndrome in pediatric patient
No full textBackground
Wolff-Parkinson-White (WPW) syndrome is a rare cardiac condition characterized by ventricular pre-excitation leading to symptoms of arrhythmia and tachycardia with a risk for sudden cardiac death (SCD). WPW is uncommon in the general population and even less frequent in the pediatric population. Diagnosis of WPW is made by electrocardiogram (ECG) with the hallmark presentation of a short PR interval, widened QRS complex, and a slurred upstroke of the QRS complex known as a delta wave. Of the patients eliciting the WPW pattern, few will progress to a symptomatic state, known as WPW syndrome, and it is unknown what causes the transition from asymptomatic to symptomatic WPW. The case demonstrates WPW syndrome in a pediatric patient and identifies a potential cause for symptom development and progression in that population.
Case Information
A 16-year-old male presented with complaints of sudden onset episodes of palpitations and tachycardia with lightheadedness. The episodes occurred several times a month, lasting for a few seconds to an hour at a time before abruptly resolving. The symptoms appeared with actions such as bending over or getting up from a bent-over position. The patient reported having similar episodes of palpitations and tachycardia four years ago, which were less frequent, less noticeable, and subsequently self-resolved. At that time, the episodes occurred twice a month. The patient does not have a history of any other cardiac conditions.
An ECG was ordered to evaluate for supraventricular tachycardia. ECG findings revealed a shortened PR interval of 102 ms (normal is 120-200 ms), a widened QRS complex of 118 ms (normal is 80-100 ms), and a delta wave indicating pre-excitation from an accessory pathway. These results confirmed the diagnosis of WPW syndrome.
The patient underwent radiofrequency ablation therapy of a low-risk left lateral accessory pathway. Treatment was successful with the resolution of WPW abnormalities on ECG post-ablation therapy. The patient was allowed to return to activity one week after treatment and continues to be asymptomatic and without abnormalities on ECG four months after.
Conclusions
WPW syndrome is an uncommon condition symptomatically characterized by arrhythmias from ventricular preexcitation with the most dangerous associated risk of SCD. The patient underwent radiofrequency ablation therapy due to presentation with a recurrence of symptomatic episodes with increased frequency and progression. In this case, the patient fits the gender profile of WPW but developed symptoms at an unusual age. There is no clear evidence on why the patient's symptoms returned after four years with more frequency, severity, and noticeability. A probable explanation is that, in a pediatric patient, changes from puberty-related heart development and physical growth led to a progression of symptoms and a more apparent reflection of the delta wave on ECG. More research is needed to identify why symptoms reoccur or worsen and how this may impact the risk calculation for SCD in patients. If puberty is a trigger, pediatric patients must be monitored for WPW pattern on ECG and onset of symptoms for prompt delivery of treatment to avoid the risk of SCD
LIMITED RESOURCES EARLY IN DEVELOPMENT ARE ASSOCIATED WITH HYPERTENSION LATER IN LIFE VIA CEREBRAL PROINFLAMMATORY CYTOKINE IL-17
No full textBACKGROUND:
Poverty is pervasive and impacts nearly 17%of children in the U.S. While it is established that adverse childhood experiences (ACEs)such as poverty are associated with hypertension later in life, the mechanisms of this trend remain unclear. The limited bed and nesting (LBN) model simulates poverty in rodents by reducing available bedding by 80% for dams to create a nest for their offspring. The impact of inflammation on hypertension across the lifespan is unknown and is the focus of this study. Specifically, we evaluated 4-week and 17-week offspring to investigate the relationship of early-life stress and inflammation.
METHOD:
Timed pregnant Sprague Dawley dams gave birth naturally and their pups were weaned for 3 weeks. Postnatal days 2-9, dams and their pups were exposed to normal bedding (CON) or the LBN treatment. Offspring were divided by age, sex, and experimental status:at4weeks {LBN males (n=6), LBN females (n=3), CON males (n=5), CON females(n=5)} and at 17 weeks{ LBN males (n=5), LBN females (n=5), CON males (n=6) and CON females (n=6)}. On day 10, all rats were returned to normal bedding. At 4/17 weeks, offspring brain samples were harvested and analyzed via colorimetric assay to assess proinflammatory cytokineinterleukin-17 (IL-17). Carotid catheterizations were performed on 17-weekoffspring and blood pressures were measured.
RESULTS:
At 4 weeks, we found a trending difference between combined male and female LBN and CON groups(495.1 ±83.3 vs 291.1 ±64.8pg/mL/mg Protein; p=0.07,ns). Male offspring with LBN treatment had a significant increase in IL-17 concentration compared to CON males (964.3 ±108.5 vs 424.0 ±86.1; p<0.01). At 17 weeks, there was no longer a trending difference between LBN and CON groups with sexes combined, but there was a significant difference between male and female offspring with LBN and CON groups combined (7761 ±1005 vs 4511 ±901pg/mL/mg Protein; p<0.05). Although not significant, LBN Males had an upward trend of IL-17 compared to CON Males, while females showed no differences. Additionally, LBN Males had an upward trend in IL-17 compared to females exposed to LBN (9294 ±1279 vs 4198 ±1595pg/mL/mg Protein; p=0.08,ns). Blood pressure readings at sixteen weeks revealed LBN males have a significant increase in BP compared to CON males(128.17±3.93 vs 110.72±3.93 mmHg, p<0.05)and females showed no change(ns).
CONCLUSION:
Elevated cerebral IL-17 in male offspring suggests an increased inflammatory response to LBN treatment compared to females who showed no change. Accordingly, male sex may be a risk factor for high inflammatory responses to stress, like poverty. The differences in cytokine expression between males and females suggests that IL-17 contributes to hypertension experienced by LBN males later in life. More research is needed to understand the timeline of physiologic responses to ACEs and to investigate opportunities to intercept the inflammation response described in this study and literature. Future research should continue to develop an understanding of sex impacts on ACEs-related stress to refine treatment recommendations in the future.This research was supported by start-up funds and the American Heart Association Early Career Development Award [AHA 18CDA34110264 (Cunningham)] and the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health Award [5R25HL007786-29(Jones)]
Social Needs Assessment in Women of Reproductive Age vs. the General Population
No full textPurpose
The objective is to identify the most prominent social needs among women of reproductive age and how it impacts their health and ability to access health care.
In 2018, the CDC reported that most preventable deaths among women of reproductive age are due to broader failures of social support. Despite comprising over half of the population and influencing the majority of healthcare decisions, there is minimal discourse within the industry regarding the distinct impact of social determinants of health (SDOH) on women.
Methods
Retrospective chart review of 1,478 completed social needs assessments among patients who visited the University of North Texas Health Science Center Central Family Medicine Clinic from June 2020 to December 2023. The PRAPARE (Protocol for Responding to & Assessing Patients’ Assets, Risks, & Experiences) screening tool, a nationally standardized tool created by the National Association of Community Health Centers, was used to assess social needs.
The data was separated into two groups: reproductive-aged women 18-45 years old (288 patients) and the remainder of the study population (1,190 patients). The remainder of the study population was comprised of 752 females and 438 males, ranging in age from 1-90 years old.
Descriptive statistical analysis was used to quantify the social needs among reproductive-aged women compared to the remainder of the study population.
Results
In each social needs category assessed by the PRAPARE screening tool, reproductive-aged women constitute a comparable or larger percentage of individuals impacted by the social need in question compared to the general population. Reproductive-aged women are most significantly affected by increased stress levels, inadequate healthcare access, difficulty obtaining childcare, unemployment, and domestic violence.
Conclusions
Reproductive-aged women have elevated and diverse SDOH-related needs, with notable disparities observed across race, ethnicity, and socioeconomic dimensions.
In order to efficiently alleviate the effects of SDOH on reproductive-aged women, stakeholders must proactively invest in enhancing the capability of healthcare providers to identify and address SDOH-related needs. This includes actively involving reproductive health care providers, who often serve as the initial and primary point of contact within the healthcare system for women in this age group.
As healthcare expenses in the United States continue to rise and disparities in health care access and outcomes persist, concentrating solely on clinical aspects of health proves inadequate. It is evident that effectively mitigating health disparities requires industry leaders to comprehend and allocate resources toward addressing the unique needs arising from social conditions
Lentiviral mediated delivery of CRISPR/Cas9 reduces intraocular pressure in a mouse model of myocilin glaucoma
No full textMutations in myocilin (MYOC) are the leading known genetic cause of primary open-angle glaucoma, responsible for about 4% of all cases. Mutations in MYOC cause a gain-of-function phenotype in which mutant myocilin accumulates in the endoplasmic reticulum (ER) leading to ER stress and trabecular meshwork (TM) cell death. Therefore, knocking out myocilin at the genome level is an ideal strategy to permanently cure the disease. We have previously utilized CRISPR/Cas9 genome editing successfully to target MYOC using adenovirus 5 (Ad5). However, Ad5 is not a suitable vector for clinical use. Here, we sought to determine the efficacy of adeno-associated viruses (AAVs) and lentiviruses (LVs) to target the TM. First, we examined the TM tropism of single-stranded (ss) and self-complimentary (sc) AAV serotypes as well as LV expressing GFP via intravitreal (IVT) and intracameral (IC) injections. We observed that LV_GFP expression was more specific to the TM injected via the IVT route. IC injections of Trp-mutant scAAV2 showed a prominent expression of GFP in the TM. However, robust GFP expression was also observed in the ciliary body and retina. We next constructed lentiviral particles expressing Cas9 and guide RNA (gRNA) targeting MYOC (crMYOC) and transduction of TM cells stably expressing mutant myocilin with LV_crMYOC significantly reduced myocilin accumulation and its associated chronic ER stress. A single IVT injection of LV_crMYOC in Tg-MYOC(Y437H) mice decreased myocilin accumulation in TM and reduced elevated IOP significantly. Together, our data indicates, LV_crMYOC targets MYOC gene editing in TM and rescues a mouse model of myocilin-associated glaucoma.These studies were supported by the National Institutes of Health (EY026177 and EY030366) and facilitated by an NIH/NEI Center Support Grant to the University of Iowa (P30 EY025580). The authors acknowledge support from NIH grant P30EY034070 and from an unrestricted grant from Research to Prevent Blindness to the Gavin Herbert Eye Institute at the University of California, Irvine
The Association of Sleep Problems with Mild Cognitive Impairment in Older Adults in the United States (US): A Cohort Study
No full textBackground: The neuroprotective aspects of sleep include improvement of memory, problem-solving, creativity, emotional processing, and judgment. Sleep problems lead to neurological damage in the hippocampus. People with sleep problems have a higher risk of developing MCI. Examining the association of sleep problems with MCI is important for surveillance and prevention efforts of dementia because MCI often leads to dementia in 10%-15% of older adults. Objective: To examine the association of type of sleep problems with MCI among older adults (age > 50 years) using Health and Retirement Study (HRS), a nationally representative prospective cohort of older adults in the US. Methods: We used baseline (2018) and follow-up (2020) data from the HRS. We restricted the analysis to adults aged 50 years or older at baseline, alive in 2020, and did not have dementia in baseline and follow-up. All sleep variables were measured at baseline and MCI was measured during the follow-up period. The dependent variable (MCI) was based on the composite measure (immediate word recall test, delayed word recall, the serial 7s, counting backward), and total scores between 7-11 represent MCI without dementia. Sleep variables were based on responses (most of the time, some, and rare/never) to the following questions: “How often do you have trouble falling asleep?”, “How often do you have trouble waking up during the night?”, “How often do you have trouble with waking up too early and not being able to fall asleep again?” and “How often do you feel rested in the morning?”. Rao- unadjusted associations were tested with Rao-Scott chi-square and adjusted associations were examined with multivariable logistic regressions. All analyses accounted for the complex survey design, and SAS 9.4 Survey procedures were used. Results: Overall, 49.1% had trouble falling asleep, 62.2% had trouble waking up, 46.1% waking up too early, and 84.1% did not feel rested in the morning. A higher percentage of adults with trouble falling asleep (18.6% vs.11.7%), trouble waking up(15.5% vs, 12.3%), and waking up too early(18.9% vs. 11.1%) had MCI compared to those without sleep problems. In logistic regression that adjusted for sex, age, race and ethnicity, living alone, education, employment, poverty, and health insurance, those with sleep problems had higher odds of MCI (trouble sleeping: aOR=1.28(95%CI:1.05 1.56), waking up too early: aOR=1.48(95%CI:1.14, 1.94) compared to those without sleep problems. However, these associations became statistically insignificant when adjusted for health status and depression. In the fully-adjusted logistic regression, never feeling rested in the morning was associated with lower odds of MCI (aOR= 0.71,95% CI=0.55, 0.91, P<0.01). Conclusion: Most older adults reported sleep problems in trouble waking up or not feeling rested in the morning. Our study adds to the conflicting evidence in the literature; some studies report no association between sleep disturbance and cognition while others even report slightly better cognitive functioning in those with sleep problems. Our study findings suggest that the association of sleep disturbances with MCI varies by type of sleep problems
Compound Heterozygous Familial Hypercholesterolemia Detected by Cascade Screening
No full textThis report outlines the case of a 13-year-old non-Hispanic White male diagnosed with compound heterozygous Familial Hypercholesterolemia (FH) with a biallelic mutation in the LDLR gene. Notable clinical manifestations of the disease were observed such as: tendon xanthomas, total LDL-C and non-HDL that were all greater than or equal to the 95th percentile for age and sex.
The patient received diagnosis for compound heterozygous FH through cascade screening by identification of his sister who had been diagnosed with heterozygous FH. However, given the patient’s family history of hypercholesterolemia and adverse cardiovascular events, both patients should have been screened by the age of 2. This paper urges healthcare systems to consider stricter implementation of universal screening protocols for FH as these patients have a significantly higher risk for adverse cardiovascular events early in life without early intervention
Determining lineages between individuals with high density mitochondrial and Y chromosomal Single Nucleotide Polymorphisms
No full textGenetic genealogy is becoming frequently used in forensic investigations in identifying criminals. However, the current genetic genealogy applications usually do not consider lineage markers (including both Y and mitochondrial DNA). Some reasons for this are genetic; few distant relatives share the same lineage markers, however lineage markers may be better than the standard autosomal markers in some scenarios. In addition, there is no study to show how to use lineage markers and what methods or thresholds should be applied in genetic genealogy. In this study, we developed a method to quickly determine if two SNP profiles are from the same paternal or material lineages by using the SNP mismatch frequency of SNPs in Y chromosomal or mitochondrial DNA. For both Y and mitochondrial SNPs, profile pairs from the same or different lineages can be decided with high accuracies (i.e., 0.380% or 0.157% error rates with Y and mitochondrial DNA, respectively). With kinship coefficient filtering based on autosomal SNPs, the accuracies of determining maternal and paternal lineage can be further improved (i.e., 0.120% or 0.057% error rates with Y and mitochondrial DNA, respectively, using a threshold of kinship coefficient > 0). This study shows that lineage markers can be very powerful tools with high accuracies to determine lineages, which could help solve cases and reduce costs for genetic genealogy investigations
Understanding the Pressure Recovery Phenomenon: A Case Study on the Discrepancies Between Echocardiography and Cardiac Catheterization in Aortic Stenosis Assessment
No full textThis detailed case study addresses the significant clinical implications of the pressure recovery phenomenon in the assessment of aortic stenosis (AS), emphasizing the discrepancies that can arise between echocardiography (ECHO) and cardiac catheterization measurements. The focal point of this study is an 80-year-old male patient with a complex medical history of coronary artery disease, hypertension, diabetes, and dyslipidemia, who underwent evaluation for AS. Our patient presented with a grade 3/6 systolic murmur loudest at the right upper sternal border consistent with AS but was asymptomatic for common cardiac-related symptoms such as angina, dyspnea, extremity edema, and syncope.
The echocardiographic assessment indicated severe AS, with the aortic valve area measured at0.79 cm² and pressure gradients at 50 mmHg (mean) and86 mmHg (peak). However, a significant divergence was observed during cardiac catheterization, which showed a considerably lower gradient of30 mmHg, indicative of moderate AS. This discrepancy is analyzed through understanding the pressure recovery phenomenon. This phenomenon occurs when blood, having flowed through a narrowed valve at high velocity (and hence low pressure), enters a larger vessel like the ascending aorta, leading to a reconversion of kinetic energy into potential energy, and thus, a recovery of pressure. This results in an overestimation of pressure gradients when using ECHO, as opposed to the direct measurements obtained via cardiac catheterization.
The study delves into the broader clinical implications of this phenomenon, particularly its influence on the categorization of AS severity and the subsequent impact on clinical management decisions. The case demonstrates how a diagnosis of severe AS based on ECHO findings might lead to considerations for surgical or percutaneous interventions, which could be unnecessary or even risky for the patient, as highlighted by the more moderate classification derived from catheterization results.
In conclusion, this study emphasizes the necessity for clinicians to be aware of the pressure recovery phenomenon and its potential to skew AS assessments. It advocates for a comprehensive, multimodal diagnostic approach, integrating both echocardiography and catheterization findings along with a thorough clinical evaluation. This approach would ensure a more accurate assessment of AS severity, leading to safer and more effective patient management strategies. The study also suggests the need for enhanced educational efforts to increase awareness and understanding of this phenomenon among healthcare providers