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    Isolation and characterization of a novel bacteriophage for Pseudomonas aeruginosa

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    Pseudomonas aeruginosa is a frequent nosocomial pathogen with emergent strains that display increasing resistance to a wide range of antibiotics including carbapenems. The goal of our study was to isolate and characterize novel bacteriophages with lytic activity against multidrugresistant (MDR) strains of P. aeruginosa. Isolation of wastewater phages was achieved through a series of plaque assays on a control strain (P. aeruginosa BAA-31). The host range of phage isolates was evaluated in vitro with MDR strains from the CDC Antibiotic-Resistance Isolate Bank. To prepare and sequence a library of phage genomes, we used Illumina's TruSeq® Nano DNA Library Prep Kit and MiSeq® system with reagent kit v2. The Center for Phage Technology's Galaxy platform was used for genome processing and annotation. We report the isolation of the novel Pseudomonas phage Jes517. Host range screening revealed 12 of 55 tested strains (21.8%) were at least partially susceptible to Jes517 with 3 showing consistently strong growth reduction in its presence. The ten closest relatives of Jes517 are in the genus Bruynoghevirus with percent identities ranging from 88.7% to 92.8%. Jes517 has a linear dsDNA genome of 45,608 bp encoding 76 open reading frames (ORFs) including three tRNAs. No known integrases, toxins, or resistance factors were identified during gene annotation. Based on its strong growth suppression of MDR P. aeruginosa and predicted lack of virulence genes, phage Jes517 makes a compelling candidate for further investigation and possible therapy

    Assessing Incontinence Reporting by Women at a Rural Texas Clinic

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    Abstract Urinary incontinence is estimated to affect between 20-45% of women in the US; a potential reason that estimates vary is due to underreporting of symptoms. In Eagle Lake, Texas, family physicians are the main source of health education concerning uro-gynecologic issues in women. No local Ob-Gyn or urology specialists practice in Eagle Lake. The two most established family physicians in Eagle Lake are male and they recently discontinued obstetric care. The goal of this project was to assess the prevalence of incontinence and reporting of symptoms by female patients in Eagle Lake, in lieu of a local Ob-Gyn or urologist. The goal of this project was to assess the prevalence of incontinence and reporting of symptoms by female patients in an Eagle Lake Family Medicine clinic, where factors exist which might present barriers to reporting. Methods A paper survey was created the Questionnaire for female Urinary Incontinence Diagnosis was used to screen for incontinence in female patients 55 years and older. Questions concerning willingness to discuss symptoms and use of UI medications were asked in multiple-choice format. Data was collected for 10 weeks, and percentages were calculated in Microsoft Excel. Results Out of 51 total participants, 50.9% screened positive for incontinence and 17.86% take bladder control medications. Out of women with incontinence, 60.71% indicated they have not brought up symptoms to a physician. Out of those who have not brought up symptoms, 13.89% indicated they would not see a physician for bladder symptoms, 13.89% indicated they would see a female physician only, and 69.44% indicated they would see either a female or male physician. Out of women with incontinence who have brought up symptoms with a physician, 27.27% reported symptoms to a female physician, 54.54% have reported symptoms to a male physician, and 18.18% reported symptoms to both a male and a female physician. Conclusions This data demonstrates that more than half of female patients 55 years and older at Rice Medical Associates are incontinent, that more than half of the incontinent women have not discussed their symptoms with a physician, and that less than twenty percent of the incontinent women are on medication for it. Some reasons for underreporting may include insufficient screening in clinic, lack of health literacy on when to seek care, and patient avoidance of discussions concerning "delicate” uro-gynecologic matters. The data shows that some women choose only to discuss bladder symptoms with a female physician, while some choose not to discuss their symptoms at all. Additionally, there were two patients who refused to complete the survey because they were uncomfortable with the topic. Due to research bias from sampling patients in a male family practitioner’s clinic, further studies should survey women outside of a healthcare setting and clarify whether reporting would be different at an Ob-Gyn office. This study indicates the need for purposeful screening for incontinence by rural family physicians, to compensate for underreporting of uro-gynecologic issues by women in areas with limited healthcare options

    Gaps in the Knowledge of Sexually Transmitted Infections in Young Adults: A Review of the Literature

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    Purpose Almost half of the 26 million sexually transmitted infections (STI) occur in young adults, although they are only 25% of the sexually active population in the US. Common STIs include chlamydia, gonorrhea, syphilis, genital herpes, Hepatitis B (HBV), Human Immunodeficiency Virus (HIV), and Human Papillomavirus (HPV). STIs are often associated with adverse health outcomes if left untreated, such as pelvic inflammatory disease, infertility, and ectopic pregnancies in women. The high rates of STIs in young adults, ages 18-25, may be due in part to a lack of knowledge about screening recommendations, symptoms, and available services for care. Because knowledge is a key factor associated with the prevention of STIs, the purpose of this study is to explore the current literature related to STI knowledge among young adults and identify the gaps in knowledge. Methods A literature review process was conducted using the following electronic databases: PubMed, Scopus, Medline, ScienceDirect, WILEY, EbscoHost. In addition to database search, the reference lists of the relevant articles were screened for titles and abstracts containing the keywords. The keywords used included: STI, STD, sexually transmitted infection, sexually transmitted diseases, knowledge, awareness, health literacy, health attitudes, information literacy, primary prevention, and secondary prevention. This retrospective search was limited to: (i) articles written in English, (ii) studies conducted in the United States, (iii) articles addressing genital herpes, HBV, HIV, HPV, chlamydia, or gonorrhea in the title or abstract, and (iv) included young adults 18-25 years old as participants. We excluded syphilis in the STI category, and the final search resulted in 41 articles that included qualitative and quantitative studies and systematic reviews. Results Gaps in the knowledge of STIs in young adults was subset into five categories: prevalence, transmission, symptoms, treatment and prevention, and testing services. Young adults lack awareness about the high STI rate in their age group, transmission factors such as skin-skin contact, or oral/genital sex, and that STIs can be asymptomatic. Many young adults have misconceptions about HPV vaccines, pre-exposure prophylaxis for HIV prevention, and condom use. Two of the most important factors to the success of STI prevention in programming are the promotion of self-efficacy and the reduction of stigma around STIs. Self-efficacy is defined as the "belief in one’s own ability to execute a particular behavior related to a specific domain of functioning.” A high level of self-efficacy in college students is one of the best predictors of STI and HIV testing and condom use. Additionally, higher levels of STI knowledge have been correlated with less stigma surrounding the diseases. Conclusion Understanding what the specific gaps are in young adults’ STI knowledge can guide college and community programs in narrowing their focus to provide complete education concerning STIs. Specifically, more programs should implement effective theory-based approaches, including those that focus on improving self-efficacy of STI prevention and treatment and decreasing the stigma around these diseases. Addressing these specific points among young adult populations may have a role in reducing the rates of STIs and preventing the adverse health outcomes

    Differential Expression of LLT1, SLAM Receptors CS1 and 2B4 and NCR Receptors NKp46 and NKp30 in Pediatric Acute Lymphoblastic Leukemia (ALL)

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    Acute lymphoblastic leukemia (ALL) represents the most common pediatric cancer. Most patients (85%) develop B-cell ALL; however, T-cell ALL tends to be more aggressive. We have previously identified 2B4 (SLAMF4), CS1 (SLAMF7) and LLT1 (CLEC2D) that can activate or inhibit NK cells upon the interaction with their ligands. In this study, the expression of 2B4, CS1, LLT1, NKp30 and NKp46 was determined. The expression profiles of these immune receptors were analyzed in the peripheral blood mononuclear cells of B-ALL and T-ALL subjects by single-cell RNA sequencing data obtained from the St. Jude PeCan data portal that showed increased expression of LLT1 in B-ALL and T-ALL subjects. Whole blood was collected from 42 pediatric ALL subjects at diagnosis and post-induction chemotherapy and 20 healthy subjects, and expression was determined at the mRNA and cell surface protein level. A significant increase in cell surface LLT1 expression in T cells, monocytes and NK cells was observed. Increased expression of CS1 and NKp46 was observed on monocytes of ALL subjects at diagnosis. A decrease of LLT1, 2B4, CS1 and NKp46 on T cells of ALL subjects was also observed post-induction chemotherapy. Furthermore, mRNA data showed altered expression of receptors in ALL subjects pre- and post-induction chemotherapy treatment. The results indicate that the differential expression of the receptors/ligand may play a role in the T-cell- and NK-cell-mediated immune surveillance of pediatric ALL.This work was supported by the Cancer Foundation of North Texas (CRFNT) with number (97313), Leukemia Texas Inc. (77313b), Institute for Cancer Research, UNTHSC (RI6062) and Team Connor Childhood Cancer Foundation

    Indications of musculoskeletal health in deceased male individuals with lower-limb amputations: comparison to non-amputee and diabetic controls

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    Individuals with lower-limb amputations, many of whom have type 2 diabetes, experience impaired musculoskeletal health. This study: (1) compared residual and intact limbs of diabetic and non-diabetic post-mortem individuals with amputation to identify structures vulnerable to injury, and (2) compared findings to diabetic and healthy control groups to differentiate influences of amputation and diabetes on musculoskeletal health. Postmortem CT scans of three groups, ten individuals each, were included: (1) individuals with transtibial or transfemoral amputations, half with diabetes (2) diabetic controls, and (3) healthy controls. Hip and knee joint spaces, cross-sectional thigh muscle and fat areas, and cross-sectional bone properties (e.g. area, thickness, geometry) were measured. Wilcoxon Signed-Rank and Kruskal-Wallis tests assessed statistical significance. Asymmetry percentages between limbs assessed clinical significance. Residual limbs of individuals with amputation, particularly those with diabetes, had significantly less thigh muscle area and thinner distal femoral cortical bone compared to intact limbs. Compared to control groups, individuals with amputation had significantly narrower joint spaces, less thigh muscle area bilaterally, and thinner proximal femoral cortical bone in the residual limb. Diabetic individuals with amputation had the most clinically significant asymmetry. Findings tended to align with those of living individuals. However, lack of available medical information and small sample sizes reduced the anticipated clinical utility. Larger sample sizes of living individuals are needed to assess generalizability of findings. Quantifying musculoskeletal properties and differentiating influences of amputation and diabetes could eventually help direct rehabilitation techniques.The Free Access Decedent Database was funded by the National Institute of Justice grant number 2016-DN-BX0144. MGF was supported by the National Institutes of Health/National Institute on Aging (T32 AG020494) and the Institute for Healthy Aging. CF was supported by the Summer Opportunities in Anatomy Research at the University of North Texas Health Science Center through the American Association for Anatomy Innovations Program

    Community perspectives on AI/ML and health equity: AIM-AHEAD nationwide stakeholder listening sessions

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    Artificial intelligence and machine learning (AI/ML) tools have the potential to improve health equity. However, many historically underrepresented communities have not been engaged in AI/ML training, research, and infrastructure development. Therefore, AIM-AHEAD (Artificial Intelligence/Machine Learning Consortium to Advance Health Equity and Researcher Diversity) seeks to increase participation and engagement of researchers and communities through mutually beneficial partnerships. The purpose of this paper is to summarize feedback from listening sessions conducted by the AIM-AHEAD Coordinating Center in February 2022, titled the "AIM-AHEAD Community Building Convention (ACBC)." A total of six listening sessions were held over three days. A total of 977 people registered with AIM-AHEAD to attend ACBC and 557 individuals attended the listening sessions across stakeholder groups. Facilitators led the conversation based on a series of guiding questions, and responses were captured through voice and chat via the Slido platform. A professional third-party provider transcribed the audio. Qualitative analysis included data from transcripts and chat logs. Thematic analysis was then used to identify common and unique themes across all transcripts. Six main themes arose from the sessions. Attendees felt that storytelling would be a powerful tool in communicating the impact of AI/ML in promoting health equity, trust building is vital and can be fostered through existing trusted relationships, and diverse communities should be involved every step of the way. Attendees shared a wealth of information that will guide AIM-AHEAD's future activities. The sessions highlighted the need for researchers to translate AI/ML concepts into vignettes that are digestible to the larger public, the importance of diversity, and how open-science platforms can be used to encourage multi-disciplinary collaboration. While the sessions confirmed some of the existing barriers in applying AI/ML for health equity, they also offered new insights that were captured in the six themes.Information reported in this publication was supported by the Office of the Director, National Institutes of Health Common Fund under award number 1OT2OD032581. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. More information can be found here: https://datascience.nih.gov/artificial-intelligence/aim-ahead

    Increased Fibronectin Serotonylation in Stretched Optic Nerve Head Astrocytes

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    Purpose: Elevated intraocular pressure contributes to glaucomatous optic nerve degeneration by inducing biomechanical stress at the optic nerve head (ONH), especially in the lamina cribrosa (LC). ONH astrocytes (ONHA) in the LC respond to biomechanical signals through extracellular matrix (ECM) remodeling activities, promoting tissue fibrosis and damage to retinal ganglion cell axons. The enzyme transglutaminase 2 (TG2) plays a role in ECM remodeling, in part, due to its ability to post-translationally modify and cross-link ECM proteins. A unique post-translational modification mediated by TG2 is "serotonylation” - the transamidation of the monoamine serotonin (5-hydroxytryptamine, 5HT) to glutamine residues on proteins. It is speculated that serotonylation contributes to fibrotic tissue remodeling, but this process has not been studied in ocular tissues or in primary glial cells. In this study, we examined changes in the serotonylation of fibronectin (FN; a major ECM glycoprotein) by ONHA after exposure to cyclic stretch. Methods: Primary human ONHA strains (n=3) were exposed to 0-12% cyclic stretch for 24h using a FlexCell FX-6000 system. Cell lysates and conditioned medium samples were collected from stretched and control cells. Serotonylation was assessed by probing for serotonin in samples of FN immunoprecipitated out of conditioned media. Protein levels for potential extra- and intra-cellular mediators of serotonylation were examined using western blotting of concentrated conditioned medium samples and cell lysates, respectively. Results: Serotonylated fibronectin was detected in ONHA. Exposure to stretch increased the amount of fibronectin that was serotonylated by 2.49-fold (p=0.0080). After stretching, extracellular FN levels were not changed. Extracellular TG2 levels were increased by 3.76-fold (p=0.0004). In cell lysates, post-stretch levels of both FN and TG2 were decreased by 5.56-fold (p=0.0181) and 2.51-fold (p=0.0441), respectively. Additionally, serotonin 2A and 2C (5HT2A, 5HT2C) receptor levels were unchanged, and serotonin transporter (SERT) levels decreased by 2.94-fold (p=0.0297). Conclusions: Increased FN serotonylation by TG2 is observed in ONHA after exposure to 24h of 0-12% cyclic stretch. Serotonylation may promote increased FN-crosslinking and fibrotic ECM remodeling, an important feature of glaucomatous pathology. The secreted TG2 – which was elevated in response to stretch – is likely to be the primary mediator of this increased serotonylation. The observed decrease in SERT may lead to increased extracellular 5HT levels, which increases the substrate availability for TG2-mediated serotonylation. Though unchanged, activity at the 5HT2A/C G-coupled protein receptors could increase the availability of intracellular calcium required for TG2 activity. Future experiments will be focused on furthering our understanding of how these proteins may interact to promote serotoynlation

    A Rare Occurrence of Cardiogenic Shock after Cardioversion: A Case Report

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    Background: Atrial fibrillation (AF) is a common cardiac arrhythmia that affects the health and lifespan of people and has been growing in prevalence with the aging population. AF leads to atrial remodeling, which increases the likelihood of developing treatment resistant AF. Risk factors for AF include obstructive sleep apnea, alcohol use, obesity, hypertension, and diabetes. Treatment consists of rhythm control, rate control, and thromboembolism prevention. If a patient fails to convert to sinus rhythm or remains symptomatic despite pharmacological treatment, the next step in management may include Direct Current Cardioversion (DCCV) or catheter ablation. DCCV restores sinus rhythm (SR) by using controlled shocks to the heart and is considered a safe and effective procedure for treating AF. Complications include arrhythmias, skin burns, and cardiac tissue damage. Following the restoration of SR, cardiac output (CO) generally improves. Cardiogenic shock is a rare occurrence after DCCV. This case report details one of these rare occurrences, where a patient with multiple comorbidities developed cardiogenic shock after DCCV for AF. Case Information: A 65-year-old male with a history of heart failure with reduced ejection fraction, AF with prior ablation, atrial flutter, dilated cardiomyopathy, obstructive sleep apnea, chronic kidney disease, and implantable cardioverter defibrillator (ICD), presented to the emergency department (ED) with symptoms of dyspnea and shortness of breath. ECG showed atrial flutter with rapid ventricular response (RVR). Urgent DCCV was performed, restoring SR but precipitating cardiogenic shock, which required intubation and vasopressors. Since stroke volume remains constant in patients with dilated cardiomyopathy, the ICD was reprogrammed to raise the HR. Thereby improving the CO and resolving the cardiogenic shock. The patient remained stable for one month but had recurrent decompensated heart failure. ECG showed AF with RVR with a HR greater than 130 bpm. The patient was cardioverted again to sinus rhythm. However, the patient's condition soon deteriorated, wherein he developed shortness of breath, orthopnea, diaphoresis, and cold extremities. He was intubated due to his respiratory distress and started on milrinone, norepinephrine, furosemide, and an amiodarone drip. He nonetheless converted to AF with RVR, compromising his CO. This was evident clinically by his decrease in urine output, despite furosemide treatment. Urgent AV node ablation with a biventricular ICD upgrade was thus recommended. Postoperatively, as his condition improved, the patient was extubated and switched to oral diuretics. Amiodarone was discontinued, and his heart failure medications were slowly reinstated. Upon discharge, the patient was referred to another facility that specializes in heart failure and transplants. Conclusion: Although DCCV is generally considered a safe and effective procedure, there are still risks associated with it. This case highlights the importance of considering underlying cardiac dysfunction in patients undergoing cardioversion for AF and the need for close monitoring and follow-up in these patients. Since not many cases showcasing these potential complications have been documented, this warrants further research to identify risk factors, complications, and ways to prevent harm to patients who may undergo DCCV

    Implementation of changing clinical practices: Prenatal syphilis screening in Texas

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    Research Appreciation Day Award Winner - SaferCare Texas, 2023 Excellence in Patient Safety Research Award - 2nd PlacePurpose: Congenital syphilis can cause negative health outcomes including stillbirths, miscarriages, birth defects, and infant death. From 2016-2020, national congenital syphilis rates have increased from 16.2 to 57.3 cases per 100,000 live births. Texas congenital syphilis rates are significantly higher than the national rates and have increased 835% from 2016-2020. Prenatal syphilis screening by providers can avert maternal and neonatal mortality and morbidity, although there are conflicts between national professional organization’s recommended guidelines and individual state screening mandates. State dissemination and clinical integration of updated screening mandates are imperative to reduce the rates of congenital syphilis in Texas. The purpose of this study is to understand the factors influencing implementation of prenatal syphilis screening guidelines into clinical practice. Methods: Prenatal providers including physicians (MD/DO) and mid-level providers (CNM/NP/PA) in Texas were recruited to participate in an in-depth interview. Recruitment strategies included social media advertising, newsletters of professional organizations, and direct email recruitment. The interview guide was based on constructs from the Consolidated Framework for Implementation Research, an implementation science theory focused on identifying determinants, or factors, that influence translation into practice. Interviews were approximately 45 minutes in length, were conducted via Zoom or phone, were audio recorded and then transcribed by a professional. Data were thematically analyzed with emergent and theory-based codes. Results: Respondents were certified nurse midwives and physicians (n=9) who discussed implementation of changing clinical practices in the context of the Texas Department of State Health Services (TDSHS) updated mandate for prenatal syphilis screening at delivery in 2019. Participants expressed difficulty with having clear communication and resources from TDSHS about changes, reliance on email updates from professional organizations for new screening recommendations, and both formal and informal colleague dialogues as sources of policy updates. Specific difficulties expressed were the confusing TDSHS website interface, ineffective email communications that are not practice-specific, and lack of data to understand the need for a change in practice for their populations. The interviewees discussed how population and professional ethics affect prenatal screening practices and the ease of changing orders once new policy changes were agreed upon by management stakeholders. Conclusion: Varied responses from participants regarding the source of TDSHS updated mandates for prenatal syphilis screening indicate that there are no universally effective methods of communication between TDSHS and clinicians to understand, be notified of, and/or implement new mandates in a timely and uniform manner. The clinicians also noted deference to national professional organizations as institutions that they could rely on for clear communication about policy recommendations that highlighted their practice needs while considering TDSHS communications as required for practice rather than a source of clinically relevant state and community health data. Understanding of how clinician perceptions of prenatal syphilis risk for their patient populations would change with relevant local statistics within TDSHS communications would further elucidate roadblocks to integration of state mandates into clinical practice. The development of context specific implementation strategies for providers in Texas can improve prenatal syphilis screening and ultimately reduce the adverse neonatal outcomes.UNTHSC Early Stage Investigator gran

    Title: Understanding Type II Diabetes Insulin Management During The COVID-19 Pandemic: Findings from a Hospital and a Clinic

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    Purpose: COVID-19 disrupted the care of people with diabetes. It is not clear how the disrupted care impacted medication safety and diabetic control outcomes. During the pandemic, questions emerged regarding whether patients experienced changes in care that led to higher glucose levels, inappropriate medication changes and poorer health outcomes. The role of strategies to control glucose, such as the use of antidiabetic drugs has been established. We examined safety issues related to the association between insulin use and diabetic control among diabetic patients during COVID-19. Results: After examining 42 patient cases, it is noted that most (55%) patients had controlled A1C (pre-Covid vs Covid-era). (55%) of patients whose A1C was < 8% (pre-Covid vs Covid era) were prescribed insulin compared to (45%) of patients who had an A1C >8% (pre-Covid vs Covid era). The cease in insulin prescribing (pre-Covid vs Covid era) increased the A1C levels for uncontrollable patients. Conclusion: During the COVID pandemic, gaps in insulin prescriptions were associated with occurrences of diabetic control status changing to uncontrolled status, indicating patient safety issues. Monitoring insulin prescribing among diabetic patients during the pandemic may identify care gaps and help to improve patient care outcomes

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