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EXAMININATION OF THE LONGITUDINAL ASSOCATION BETWEEN ALCOHOL-INDUCED BLACKOUTS AND AUDIT SCORES AND THE MODERATING EFFECTS OF IMPULSIVITY AMONG ADOLESCENTS AND YOUNG ADULTS
No full textPurpose: Adolescent and young adult alcohol consumption and related consequences present persistent public health concern and research highlights the role that alcohol-induced blackouts (AIB) may have on the development of alcohol use disorders. Moreover, impulsivity, specifically premeditation and urgency, are noted to have significant associations with drinking. However, less is known about these associations over time among adolescents and young adults. Therefore, this study examined longitudinal associations between AIB and hazardous alcohol use risk (AUDIT scores) in adolescents and young adults, while exploring the moderating effects of premeditation and urgency. Methods: Participants were recruited for a longitudinal ecological momentary assessment (EMA) study examining cognitions and alcohol use. Data were collected at baseline and 12-month follow-up from participants who reported past month alcohol use. The analytic sample consisted of 556 participants (58.6% females; 70.8% White Non-Hispanic, ages 15-25 [mean = 21.5, SD = 2.5]). Data were analyzed using generalized linear models (GLM). Results: Results revealed a significant association between baseline AIB and AUDIT scores at 12-month follow-up such that a one-unit increase in AIB scores was associated with a 12% increase in residual change of AUDIT scores (RR = 1.12, p = .001). Premeditation was inversely associated with AUDIT scores, such that on average, a one-unit increase corresponded to an 8% relative reduction in AUDIT scores (RR = 0.92, p = .032). Finally, urgency was not significantly associated with AUDIT scores (RR = 1.07, p = .053). Premeditation, but not urgency, significantly moderated the effect of AIB on change in AUDIT scores such that for those with relatively higher premeditation scores, a one-unit increase in AIB corresponds to a 22% increase in AUDIT scores (RR = 1.13, p= .009). Conclusion: Findings suggest a significant association between AIB and AUDIT scores one year later, controlling for baseline AUDIT scores. Furthermore, the moderating effect of premeditation suggests that those with higher premeditation who are still engaging in AIB may be doing so with intentions to engage in high-risk drinking. Targeting prevention programs, towards adolescents and young adults with a history of AIB, especially those who with elevated premeditation, may be effective in mitigating the risk of alcohol use disorder development
Consumer Needs for Long-Term Services and Supports and the Road to Improving the Texas No Wrong Door System
No full textPurpose: Long-term services and supports (LTSS) encompass a broad range of medical and personal care assistance needed by individuals who are unable to perform self-care tasks due to aging, chronic illness, or disability. The No Wrong Door (NWD) System is a statewide network that coordinates the system of access to long-term services and supports. As an offshoot of the person-centered planning movement, the NWD System is premised on ensuring that no matter where individuals first interact with the system, they are guaranteed comprehensive information, assessment, and services. The primary goal of this work is to identify strategies to optimize coordination between and awareness of the entry points of this system. The evaluation will help the Texas Health and Human Services Commission create a consumer-driven, cost-effective, and efficient system. Methods: Qualitative input was captured through listening sessions in five Texas cities (i.e. Amarillo, El Paso, Fort Worth, Pharr, and San Antonio) which were supplemented with a statewide survey launched in September 2023 to derive understanding from experiences with the NWD System. Target audiences included people with disabilities, veterans, adults aged 50 and over, family caregivers, and LTSS providers. Several tools (e.g., telephone, mail, and Internet) were utilized for increased survey accuracy and response rate. The survey was distributed in both English and Spanish, and a specific QR code and survey link was incorporated to track responses. Results: Of 4,185 survey respondents, 69% self-identified within the target group (excluding LTSS providers), and 61% expressed a need for LTSS in the past year. Of the 52% who applied for LTSS, 44% stated use of LTSS daily, and 14% weekly. The top three problems accessing LTSS include a confusing system, long wait times for services, and not knowing where to get help. 79% of consumers were unaware of the NWD System; 2% unsure. Of the 19% aware, 45% felt very or somewhat uninformed about the system in their community. The reasonability of time spent applying for services, ease of applying for services, and timeliness in handling service concerns were among the lowest-scoring statements regarding the system. Conclusions: Our results form the blueprint for facilitating access to care at the community and agency levels throughout Texas to ensure vulnerable populations obtain a high quality of life. Recommendations for the NWD system include effective community outreach and streamlined application processes for services and supports.Texas Health and Human Services Commissio
Impact of Annexin A2 on virus life cycles
No full textDue to the limited size of viral genomes, hijacking host machinery by the viruses taking place throughout the virus life cycle is inevitable for the survival and proliferation of the virus in the infected hosts. Recent reports indicated that Annexin A2 (AnxA2), a calcium- and lipid-binding cellular protein, plays an important role as a critical regulator in various steps of the virus life cycle. The multifarious AnxA2 functions in cells, such as adhesion, adsorption, endocytosis, exocytosis, cell proliferation and division, inflammation, cancer metastasis, angiogenesis, etc., are intimately related to the various clinical courses of viral infection. Ubiquitous expression of AnxA2 across multiple cell types indicates the broad range of susceptibility of diverse species of the virus to induce disparate viral disease in various tissues, and intracellular expression of AnxA2 in the cytoplasmic membrane, cytosol, and nucleus suggests the involvement of AnxA2 in the regulation of the different stages of various virus life cycles within host cells. However, it is yet unclear as to the molecular processes on how AnxA2 and the infected virus interplay to regulate virus life cycles and thereby the virus-associated disease courses, and hence elucidation of the molecular mechanisms on AnxA2-mediated virus life cycle will provide essential clues to develop therapeutics deterring viral disease.This work was supported, in whole or in part, by the National Institutes of Health grant R21CA283524 (to PC) and the UNTHSC Seed Grant to PC and IWP
Effectiveness of provider communication training for increasing human papillomavirus vaccine initiation at a safety-net health system
Get PDFBACKGROUND: Strong provider recommendation can increase uptake of human papillomavirus (HPV) vaccination. Therefore, we developed and implemented a provider education intervention on communication strategies for recommending HPV vaccination with clinic-level audit and feedback (HPV: Communicating about HPV to Adults and Teens [HPV CHAT]). We aimed to evaluate the effect of HPV CHAT on HPV vaccine uptake in seven family medicine and pediatric clinics in a large urban health system (USA). METHODS: We used a quasi-experimental design, where the eligible population included people aged 9-26 years with at least one encounter in June 2020-February 2023 at one of the participating community health clinics. We used interrupted time-series analysis to assess changes in the prevalence of HPV vaccine uptake. We used segmented Poisson regression with a log link function to estimate prevalence ratios (PR) and 95% confidence limits (CL) for level (immediate) and slope (over time) changes with adjustment for seasonality using Fourier transformation. RESULTS: Our study population comprised 60,328 observations in which the median age was 17 years (interquartile range: 13-21). A majority (58%) were female and 87% were racial/ethnic minorities. Overall, we observed no sizeable effect of the intervention on HPV vaccination uptake. Nonetheless, heterogeneity was observed by age group with modest increases in individuals aged 9-12 and 13-17 years. CONCLUSION: Our provider feedback intervention had minimal effect on increasing prevalence of HPV vaccination in seven family medicine and pediatric clinics. Novel strategies are needed to address provider barriers related to HPV vaccination.This project was supported by The University of Texas MD Anderson Cancer Center
Ocular Inflammation and Oxidative Stress as a Result of Chronic Intermittent Hypoxia: A Rat Model of Sleep Apnea
No full textObstructive sleep apnea (OSA) is a sleep disorder characterized by intermittent complete or partial occlusion of the airway. Despite a recognized association between OSA and glaucoma, the nature of the underlying link remains unclear. In this study, we investigated whether mild OSA induces morphological, inflammatory, and metabolic changes in the retina resembling those seen in glaucoma using a rat model of OSA known as chronic intermittent hypoxia (CIH). Rats were randomly assigned to either normoxic or CIH groups. The CIH group was exposed to periodic hypoxia during its sleep phase with oxygen reduction from 21% to 10% and reoxygenation in 6 min cycles over 8 h/day. The eyes were subsequently enucleated, and then the retinas were evaluated for retinal ganglion cell number, oxidative stress, inflammatory markers, metabolic changes, and hypoxic response modulation using immunohistochemistry, multiplex assays, and capillary electrophoresis. Statistically significant differences were observed between normoxic and CIH groups for oxidative stress and inflammation, with CIH resulting in increased HIF-1alpha protein levels, higher oxidative stress marker 8-OHdG, and increased TNF-alpha. Pyruvate dehydrogenase kinase-1 protein was significantly reduced with CIH. No significant differences were found in retinal ganglion cell number. Our findings suggest that CIH induces oxidative stress, inflammation, and upregulation of HIF-1alpha in the retina, akin to early-stage glaucoma.The authors declare no conflicts of interest
Sex-dependent effects of chronic intermittent hypoxia: implication for obstructive sleep apnea
No full textBACKGROUND: Obstructive sleep apnea (OSA) affects 10-26% of adults in the United States with known sex differences in prevalence and severity. OSA is characterized by elevated inflammation, oxidative stress (OS), and cognitive dysfunction. However, there is a paucity of data regarding the role of sex in the OSA phenotype. Prior findings suggest women exhibit different OSA phenotypes than men, which could result in under-reported OSA prevalence in women. To examine the relationship between OSA and sex, we used chronic intermittent hypoxia (CIH) to model OSA in rats. We hypothesized that CIH would produce sex-dependent phenotypes of inflammation, OS, and cognitive dysfunction, and these sex differences would be dependent on mitochondrial oxidative stress (mtOS). METHODS: Adult male and female Sprague Dawley rats were exposed to CIH or normoxia for 14 days to examine the impact of sex on CIH-associated circulating inflammation (IL-1beta, IL-6, IL-10, TNF-alpha), circulating steroid hormones, circulating OS, and behavior (recollective and spatial memory; gross and fine motor function; anxiety-like behaviors; and compulsive behaviors). Rats were implanted with osmotic minipumps containing either a mitochondria-targeting antioxidant (MitoTEMPOL) or saline vehicle 1 week prior to CIH initiation to examine how inhibiting mtOS would affect the CIH phenotype. RESULTS: Sex-specific differences in CIH-induced inflammation, OS, motor function, and compulsive behavior were observed. In female rats, CIH increased inflammation (plasma IL-6 and IL-6/IL-10 ratio) and impaired fine motor function. Conversely, CIH elevated circulating OS and compulsivity in males. These sex-dependent effects of CIH were blocked by inhibiting mtOS. Interestingly, CIH impaired recollective memory in both sexes but these effects were not mediated by mtOS. No effects of CIH were observed on spatial memory, gross motor function, or anxiety-like behavior, regardless of sex. CONCLUSIONS: Our results indicate that the impact of CIH is dependent on sex, such as an inflammatory response and OS response in females and males, respectively, that are mediated by mtOS. Interestingly, there was no effect of sex or mtOS in CIH-induced impairment of recollective memory. These results indicate that mtOS is involved in the sex differences observed in CIH, but a different mechanism underlies CIH-induced memory impairments. Sleep apnea is a common sleeping condition in adults with a wide range of symptoms that include inflammation, oxidative stress, memory problems, anxiety, and compulsivity. Men are diagnosed with sleep apnea more often than women. Although there is limited information on how sleep apnea affects men and women differently, previous studies suggest that women may exhibit different sleep apnea symptoms than men. To examine the impact of male and female sex on common sleep apnea symptoms, we exposed adult male and female rats to a model of sleep apnea called chronic intermittent hypoxia (CIH). We found that many effects of CIH were different in males and females. CIH females had increased inflammation and motor problems, whereas CIH males had increased oxidative stress and compulsivity. To investigate the reason for these CIH sex differences, we blocked mitochondrial oxidative stress. Blocking mitochondrial oxidative stress decreased CIH associated sex differences. However, blocking mitochondrial oxidative stress had no impact on CIH-induced memory impairment that was observed in male and female rats. Our findings support previous reports that suggest that women exhibit different sleep apnea symptoms than men. Further, we extend these findings by showing that mitochondrial oxidative stress is involved in these sex differences. Clinically, patients diagnosed with sleep apnea are typically treated with continuous positive airway pressure (CPAP) machines, which have high rates of non-compliance (15-40%). Therefore, understanding why sleep apnea is causing these symptoms will be important in developing therapeutics.This study was supported by NIH R01 NS0091359 and UNTHSC Seed Grant funding to RLC, AHA 22PRE-900431 to JJG, AHA 22POST-903250 to JLB, and NIH T32 AG020494 to SM
The Expression of Adipogenic Marker Is Significantly Increased in Estrogen-Treated Lipedema Adipocytes Differentiated from Adipose Stem Cells In Vitro
No full textLipedema is a chronic, idiopathic, and painful disease characterized by an excess of adipose tissue in the extremities. The goal of this study is to characterize the gene expression of estrogen receptors (ERalpha and ERbeta), G protein-coupled estrogen receptor (GPER), and ER-metabolizing enzymes: hydroxysteroid 17-beta dehydrogenase (HSD17B1, 7, B12), cytochrome P450 (CYP19A1), hormone-sensitive lipase (LIPE), enzyme steroid sulfatase (STS), and estrogen sulfotransferase (SULT1E1), which are markers in Body Mass Index (BMI) and age-matched non-lipedema (healthy) and lipedema ASCs and spheroids. Flow cytometry and cellular proliferation assays, RT-PCR, and Western Blot techniques were used to determine the expression of ERs and estrogen-metabolizing enzymes. In 2D monolayer culture, estrogen increased the proliferation and the expression of the mesenchymal marker, CD73, in hormone-depleted (HD) healthy ASCs compared to lipedema ASCs. The expression of ERbeta was significantly increased in HD lipedema ASCs and spheroids compared to corresponding healthy cells. In contrast, ERalpha and GPER gene expression was significantly decreased in estrogen-treated lipedema spheroids. CYP19A1 and LIPE gene expressions were significantly increased in estrogen-treated healthy ASCs and spheroids, respectively, while estrogen upregulated the expression of PPAR-Upsilon2 and ERalpha in estrogen-treated lipedema-differentiated adipocytes and spheroids. These results indicate that estrogen may play a role in adipose tissue dysregulation in lipedema.This work was supported by the Lipedema Foundation (LF 39_21)
Impact of Age on Cognitive Testing Practice Effects and Cardiorespiratory Responses
No full textObjective: This study tested the hypothesis that healthy aging attenuates cognitive practice effects and, consequently, limits the familiarity-associated reductions in heart rate (HR) and breathing frequency (BF) responses during retesting. Methods: Twenty-one cognitively normal older and younger adults (65 +/- 2 vs. 26 +/- 1 years old) participated in the study. Mini-Mental State Examination (MMSE), Digit-Span-Test (DST), Trail Making Test (TMT-B), and California Verbal Learning Test (CVLT-II) were administered twice at 3-week intervals, while HR and BF were monitored by electrocardiography and plethysmography, respectively. Results: Cognitive performances were not affected by the age factor, and the retest factor only affected CVLT-II. HR and BF increased only in the younger adults (p < .01) during cognitive tests; retesting attenuated these responses (retest factor p < .01). Long-delay free-recall in CVLT-II was unchanged in cognitively normal older versus younger adults. Healthy aging did not diminish short-term memory assessed by DST and CVLT-II short-delay or long-delay free-recalls. Conclusions: Only CVLT-II, but not MMSE, DST or TMT-B, demonstrated cognitive retesting practice effects in the younger and older adults. Cognitive testing at 3-week intervals in cognitively normal older and younger subjects revealed divergent cardiorespiratory responses to MMSE, DST, and TMT-B cognitive testing, particularly HR, which increased only in younger adults and to a lesser extent during retesting despite the absence of practice effects.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Funded by grant R01-AG076675 from National Institute on Aging
Upper Gastrointestinal Bleed with an Unusual Etiology: A Difficult Case with Unclear Imaging Findings.
No full textBackground: Atrial fibrillation (AF) is a cardiac arrhythmia which can be managed with AF ablations, used to control aberrant electrical activity. A serious complication of ablations includes atrioesophageal fistulas (AEF), with clinical manifestations of hematemesis, fever, neurological deficits, and mental status changes. A majority of documented cases utilize computed tomography (CT) scans which demonstrate the presence of a fistula, but there remains a paucity of AEF cases with unclear imaging findings. Case Presentation: A 63-year-old Caucasian male with symptomatic persistent AF underwent radiofrequency ablation with PVs and left atrial posterior wall isolation on December 12, 2016. The patient tolerated the procedure well. On January 11, 2017, the patient returned to the emergency department with hematemesis one day prior. The patient reported chills, nausea, mild headache and a temperature of 103.2F. Patient reported taking ibuprofen with no relief. Vital signs at admission: T 98.5 F, BP 107/57, HR 62 bpm, and oxygen saturation of 100% on room air. PE: normal with no neurologic deficits. Labs: CBC indicated leukocytosis with neutrophilic shift and bandemia, thrombocytopenia, and low hemoglobin. CMP: low serum albumin and total protein. Coagulation studies: elevated aPTT and INR. Serum troponin I: minimally elevated. ECG: nonspecific T wave changes. CXR: no evidence of cardiopulmonary disease. Cranial CT scan: nonspecific bilateral subcortical frontal lobe white matter changes. Chest CTA with contrast was recommended by the EP to assess for an AEF and revealed no atrial wall defects. Gastroenterology was consulted for an upper GI bleed (UGIB) caused by NSAID usage based on imaging findings. Patient further experienced vision changes, confusion, chills, and myalgias. Blood Gram stain was positive for gram-positive cocci. Patient was started on a course of piperacillin-tazobactam and vancomycin. Magnetic Resonance Imaging illustrated bihemispheric ischemic infarctions. EGD revealed a protuberance with a small opening thirty centimeters from the incisors. Patient continued to deteriorate, and a repeat CT angiogram displayed a possible atrial wall defect but no overt fistula, pneumomediastinum, or contrast media within the esophagus. Based on high clinical suspicion of an AEF, a cardiothoracic surgery consult was requested. A cardiothoracic surgery was performed with repair of the left atrium and esophageal fistula. A 2-3 millimeter punctate defect was present between the left and right inferior pulmonary veins. Fibrinous adhesions were present on the anterior esophagus at the level of the left atrium. A punctate mucosal perforation was present in the esophageal wall measuring 2-3 millimeters in diameter. A pericardial patch was placed. The patient tolerated the procedure well and was transferred to the cardiovascular ICU. Post-operatively, the patient developed sepsis, delirium, and difficulty swallowing and was placed on tube feeding. Over the following days, mental status improved. Final culture results on postoperative day seven confirmed Streptococcus oralis, Streptococcus mitis, and Granulicatella adiacens and were treated with IV ceftriaxone outpatient. On postoperative day nine, the patient was discharged with no neurological deficits. Conclusion: This case highlights the importance of including AEFs within differential diagnoses of UGIB given recent AF ablations when imaging results are inconclusive