Marantic Endocarditis: A Case Report
marantic endocarditis; valvular vegetations; anticoagulation; transesophageal echocardiogram; transthoracic echocardiogram
Non-bacterial thrombotic endocarditis (NBTE), or Marantic Endocarditis, is a rare and complex condition characterized by a spectrum of non-infectious lesions of the heart valves, most commonly the mitral and aortic valves. While the pathogenesis is not entirely known, the presence of these sterile vegetations is associated with hypercoagulable states like cancer, autoimmune diseases, and HIV. Diagnosing marantic endocarditis is difficult and often discovered on autopsy; therefore, maintaining a high index of suspicion is pivotal. We present a case of an 84-year-old male with no significant past medical history who was recently diagnosed with new-onset atrial fibrillation and was consequently started on digoxin. Follow-up lab work demonstrated elevated digoxin levels, and he was sent to the emergency department (ED). Lab work in the ED revealed elevated proBNP and troponin levels, resulting in his admission for further evaluation and management. A transthoracic echocardiogram (TTE) showed valvular vegetation. The patient was started on empiric antibiotics due to suspicion of infective endocarditis. A transesophageal echocardiogram (TEE) done after completion of antibiotics showed persistence of vegetations, leading to a diagnosis of NBTE. The patient was discharged on anticoagulant therapy. His follow-up TEE echocardiogram did not detect any cardiac vegetations. Further evaluation of the patient did not reveal any underlying etiology for the diagnosis of his NBTE.
Sodhi A; Avasarala VS; Salmen N; Doshi P; Lisy T
Journal of Medical Sciences at NEOMED
2024
n/a
A Pilot Survey and Workshop Program to Understand and Address Sexual Harassment/Assault on a Health Professions Campus
sexual harassment; Title IX; campus resources
Sexual assault is prevalent on U.S. academic campuses, with 13% of students experiencing rape or sexual assault,1 even with Title IX programming and support.2 We sought to understand health professional student experiences (e.g. assault/reporting habits) and identify knowledge gaps in campus resources to improve academic environments and reporting practices. As a pilot study, all students (approx. 980) on a small regional health professions university were invited to respond to an anonymous, 14-item mixed methods survey aimed at gathering information about student sexual harassment/assault experiences and reporting behaviors. Surveys were distributed to included MD, PharmD, and Masters candidates in Graduate Studies via a Qualtrics link to their institutional email addresses. Thirty-six students (3% of the student body) participated. After synthesizing the results of the survey in a qualitative manner, we collaborated with the campus Title IX Resource Officer to develop a workshop and presentation aimed at addressing the issues identified in survey results, as well as providing general information on Title IX. The workshop was open to all students on the health professions campus, regardless of survey participation. After the workshop, participants (n=12) were invited to respond to a post-workshop survey including the same general knowledge questions as the initial survey to assess student learning in a pre-test/post-test manner. Due to low participation in the post-workshop survey (n=3), the results were not synthesized. 87.5% (n=7 of 8) of respondents who identified as a victim of sexual harassment/assault did not report the incident(s) because of: emotional difficulty, scrutiny/gossip, unsure harassment is sexual, fear of perpetrator, perceived lack of police/university assistance, and protection of perpetrator from professional/ criminal consequences, amongst other reasons. 67% (n=24 of 36) of respondents did not know or were unsure of the process for reporting sexual harassment or assault, and 76% (n=27 of 36) were not aware of the Title IX office for reporting. All participating students were more likely to report sexual harassment/ assault if the reporting process was anonymous, and 58% (n=21 of 36) of respondents indicated they would like to learn more about the reporting process. Due to the number of reasons why health professions students do not report sexual harassment and assault and the lack of knowledge about Title IX, it is critical that academic environments recognize these issues and improve awareness. Despite low study participation, in both the initial survey and subsequent workshop, pilot study results were sent to a Task Force on Mistreatment for further campus wide action to improve Title IX awareness and creating a safe reporting environment. A multi-institutional study is recommended.
Wani R; Aultman J
Journal of Medical Sciences At NEOMED
2024
n/a
Myxedema Coma: A Rare Manifestation of Hypothyroidism
myxedema coma; hypothyroidism; levothyroxine
Myxedema coma is a severe expression of longstanding uncontrolled hypothyroidism. Myxedema coma can be life-threatening and affects a multitude of organs, such as the heart, lungs, and kidneys. Patients typically present with altered mental status and abnormal vital signs. Prompt treatment with thyroid hormone replacement is crucial in the survival of patients with a myxedema coma. This patient case involves a 62-year-old female who presented to the emergency department with a chief complaint of altered mental status. The patient had symptoms and laboratory values consistent with a myxedema coma. The patient was given levothyroxine intravenously, which led to a drastic improvement in symptoms.
Tulcewicz P; Posendek K
Journal of Medical Sciences at NEOMED
2024
n/a
TURMERIC - The Golden Herb!
curcumin; inflammation; oxidative stress; polyphenols; turmeric
The curry spice, turmeric, is used to provide color and flavor to food, as well as for its health benefits. Turmeric contains many polyphenolic compounds known as curcuminoids, with curcumin being the most prominent curcuminoid. In this perspective, the health benefits of turmeric curcuminoids are highlighted. Specifically, this perspective summarizes the source, history, and the general use of turmeric. The pharmacology, especially the antioxidative and anti-inflammatory properties, safety, and the pharmacokinetic profile, as well as the therapeutic potential of curcuminoids in several disease conditions is discussed. The development of semi-synthetic forms and novel formulations for delivery of curcuminoids is mentioned. This article reflects upon the current status of turmeric use and the potential challenges, as well as future steps needed for development of curcuminoids as therapeutic agents in the clinic.
Darvesh AS
Journal of Medical Sciences at NEOMED
2024
n/a
Knowledge Concerning Physical Therapy Interventions for Neck Pain Among Local Referring Physicians for Interdisciplinary Care Improvement: A Follow-Up Survey on Clinical Practice Guideline Usage
physical therapy, clinical practice guidelines, exercise, physician education, manual therapy
Neck pain is an orthopedic condition for which physicians commonly refer to physical therapy (PT). Limited data exists on the extent of knowledge among referring physicians regarding PT clinical practice guideline (CPG) interventions. Our hypothesis is that physician knowledge about PT CPG interventions is low. The purpose of this study is to determine local physician knowledge about evidence-based PT treatment for neck pain. Local physicians (n=500) were surveyed within one hospital system to determine their knowledge of PT when referring patients with neck pain. Data recorded included specialty, years of practice, frequency of treating neck pain, frequency of referring neck pain to PT, interventions that the physicians desire to see being used (pick five), interventions that are being used (pick five), impression that PT is helpful, and willingness for education. Physician responses (n=23) were most commonly from family medicine (n=11) and orthopedic surgeons (n=6). Neck pain was frequently treated by physicians and referred to PT. The most desired interventions included upper trapezius stretches (65%), soft tissue massage (56%), and cervical mobilization (47%). Lowest desired interventions included thoracic manipulation (4%) and using ice (17%). Interventions that physicians see being used on their patients include general upper extremity (UE) exercise (56%), cervical mobilization (39%), electrical stimulation (34%), soft tissue massage (30%), and dry needling (30%). Most physicians were open to further education regarding neck pain treatment (73%). Many of the surveyed physicians commonly refer to PT for neck pain and believe PT to be helpful for neck pain. Among the interventions that physicians listed, support from CPG recommendations for PT treatment was mixed, only partially supporting our hypothesis. Further research is needed to determine impact on interdisciplinary care and patient outcomes.
Baumann AN; Patil N
Journal of Medical Sciences at NEOMED
2024
n/a
Paraneoplastic Cerebellar Degeneration Associated with Metastatic Neuroendocrine Tumor
paraneoplastic cerebellar degeneration; neuroendocrine tumor; dipeptidyl-peptidase-like protein 6 antibody; glutamic acid decarboxylase -65; type voltage gated calcium channel antibody
Paraneoplastic cerebellar degeneration (PCD) is a rare disorder characterized by progressively worsening cerebellar dysfunction associated with onconeural antibodies. Commonly, these antibodies are anti-neuronal nuclear antibody type 1 (ANNA-1, also known as anti-Hu) and Purkinje cell cytoplasmic antibody (PCA-1, also known as anti-Yo). Here, we report a unique presentation of PCD. A 60-year-old man presented to the outpatient clinic with worsening ataxia. Over the span of three weeks, he progressed to walking with a cane and then required a wheelchair. Upon examination, the patient was found to have moderate dysmetria and substantial gait and truncal ataxia. Magnetic resonance imaging (MRI) did not show any cerebellar atrophy or acute intracranial process; however, CT chest/abdomen and pelvis identified a right hepatic lesion with biopsy demonstrating a metastatic small-cell neuroendocrine tumor (NET) of unknown primary origin. The serum paraneoplastic antibody panel revealed three positive antibodies: dipeptidyl-peptidase–like protein 6 (anti-DPPX) antibody, glutamic acid decarboxylase-65 (GAD-65) antibody, and P/Q-type voltage-gated calcium channel (VGCC) antibody simultaneously. This is the first case of PCD with simultaneous detection of multiple antibodies in the context of a metastatic neuroendocrine tumor (NET).
Patel A; Brooks AK; Itrat A
Journal of Medical Sciences at NEOMED
2024
n/a
Enhancement of Early-Stage Cancer Detection by Liquid Biopsy using Nanoparticle Platforms
early-stage cancer; gold nanoparticles; quantum dots; magnetic nanoparticles
Cancer has consistently been a public health burden for many decades, responsible for high mortality and morbidity rates worldwide. Effective cancer diagnostic methods are crucial to improving patients' survival and timely implementation of therapeutic and surgical interventions. Current diagnostic technologies are much more efficient in detecting cancer at late stages (stages 3 and 4) than early stages (stages 1 and 2), typically in solid tumor-based cancers. Meanwhile, cancer metastasis is a prominent feature of late stages, which poses a significant barrier to the effectiveness of therapeutic and surgical interventions. Thus, detecting early-stage cancer is crucial when the disease remains within the primary site. Though liquid biopsy has gained attention for noninvasive and low-cost diagnosis, cancer biomarkers present at early stages are at concentrations too low for conventional methods to detect with specificity. The low concentrations of early-stage cancer biomarkers pose a significant barrier in diagnosing patients with high sensitivity and specificity. This drawback can be addressed through an innovative combination of diagnostic nanoparticle platforms with liquid biopsy procedures. The strategy has been demonstrated to remarkably improve the efficiency of detecting early-stage biomarkers at the lowest concentration possible, i.e., decreasing the limit of detection (LOD). This review will assess the utility of various nanoparticle platforms in developing novel diagnostic techniques for early-stage cancer detection.
Ghanta P; Winschel T; Oyewumi MO
Journal of Medical Sciences at NEOMED
2023
n/a
The Burden of Leadership: a Survey of Burnout Experiences Among Psychiatry Program Directors
Objective: The objectives of this study were to examine the prevalence of burnout, specify contributors to and protective factors against burnout, and gather suggestions to improve well-being in psychiatry Program Directors.
Methods: A survey regarding burnout and wellness was distributed to psychiatric Program Directors through the email listserv of the American Association of Directors of Psychiatric Residency Training (AADPRT).
Results: The survey response rate was 273 responses out of 880 members surveyed (31%). The majority of respondents were current residency or fellowship Program Directors or Associate Program Directors or had another current educational role (93%, 227/245). Almost half of current Program Directors or Associate Program Directors reported feeling burned out almost daily or once a week (44%, 93/210). These Program Directors reported a desire to resign (77%), experienced discrimination within the past 5 years (66%), and struggled with finding meaning in their job (44%). The most frequently endorsed contributors to burnout were increasing administrative burden and insufficient support.
Conclusions: The survey findings confirm that burnout characteristics are common among respondents, associated with a desire to resign and a struggle to find meaning in the highly demanding position of Program Director or Associate Program Director. Advocacy for resources, decreased administrative overload, and increased protected time would enhance well-being in Program Directors. Most striking was the frequency of discrimination reported and its relationship to burnout. Departments may benefit from a careful review of policies, procedures, and training to decrease hostile workplaces for women, international medical graduate, and under-represented in medicine Program Directors.
Sallie G De Golia
Lillian Joy Houston
Vishal Madaan
Isheeta Zalpuri
Randon Welton
Carol Bernstein
Sourav Sengupta
Muhammad A Chaudhry
Donna M Sudak
DOI: 10.1007/s40596-022-01675-4
Academic psychiatry
2023 Apr
English
Empowering Students Who Are Breastfeeding a Child While Enrolled in Pharmacy School
Pharmacy students wishing to maintain their breastfeeding relationship with their child while also excelling within a Doctor of Pharmacy program require important resources and a culture of support. This Commentary examines the challenges that pharmacy students who are breastfeeding face, highlights the importance of pharmacy schools and colleges providing breastfeeding and lactation support, and identifies best practices for implementing support measures for these students. We aim to guide institutions in not only supporting breastfeeding students but empowering them to excel personally, professionally, and academically.
Mary E Fredrickson
Jaclyn Boyle
M Petrea Cober
Cynthia A King
DOI: 10.5688/ajpe9023
American journal of pharmaceutical education
2023 Apr
English
Generational situatedness: Challenging generational stereotypes in health professions education
Purpose: Use of generation theory is pervasive within health professions education (HPE) literature, yet its application perpetuates unfounded generalizations that disadvantage learners. The objectives of this thematic analysis are first, to understand how generation theory is applied to 'Generation Z' HPE students and second, to propose a more productive framework for approaching evolutions within HPE.
Methods: A literature search was conducted to identify HPE publications pertaining to Gen Z learners. A thematic analysis was undertaken to identify a priori themes and uncover new themes.
Results: Qualitative analysis revealed evidence of three a priori themes as well as four newly identified themes across our sample.
Conclusion: The near ubiquity of essentialism and generational othering across our sample illustrates the ongoing challenges posed by generationalism in HPE discourse. While traces of generational humility and generational situatedness suggest a more holistic response to evolving student populations, we nevertheless discourage the continued use of generation theory to guide HPE pedagogy and instead urge educators to resist essentializing generalizations by thinking comprehensively about what evolutions in HPE must occur if we are to best prepare our students to practice in present and future healthcare settings.[Box: see text].
Rachel Conrad Bracken
Mary E Fredrickson
L Austin Fredrickson
Michael Appleman
DOI: 10.1080/0142159X.2022.2135428
Medical teacher
2023 Apr
English
Response to sirolimus in capillary lymphatic venous malformations and associated syndromes: Impact on symptomatology, quality of life, and radiographic response
Background: Capillary lymphatic venous malformations (CLVM) and associated syndromes, including Klippel-Trenaunay syndrome (KTS) and congenital lipomatous overgrowth, vascular malformation, epidermal nevi, skeletal, and spinal syndrome (CLOVES), are underrecognized disorders associated with high morbidity from chronic pain, recurrent infections, bleeding, and clotting complications. The rarity of these disorders and heterogeneity of clinical presentations make large-scale randomized clinical drug trials challenging. Identification of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [gene]) mutations in CLVM has made targeted medications, such as sirolimus, attractive treatment options. The aim of this study was to investigate the safety and efficacy of sirolimus therapy in CLVM.
Procedure: A combined prospective and retrospective cohort of pediatric and young adult patients with CLVM treated with sirolimus was evaluated for disease response, including symptom improvement, quality of life (QOL), and radiologic response. Sirolimus dosing regimens and toxicities were also assessed.
Results: Twenty-nine patients with CLVM, including KTS and CLOVES, were included. Ninety-three percent of patients reported improved QOL, and 86% had improvement in at least one symptom. Most significantly, improvement was noted in 100% of patients with bleeding and 89% with thrombotic complications with corresponding decreases in mean D-dimer (p = .008) and increases in mean fibrinogen (p = .016). No patients had progressive disease on sirolimus. Most common side effects included neutropenia, lymphopenia, infection, and aphthous ulcers/stomatitis. No toxicities were life-threatening, and none required long-term discontinuation of sirolimus.
Conclusion: Sirolimus appears to be effective at reducing complications and improving QOL in patients with CLVM and associated syndromes. In this patient cohort, sirolimus was well tolerated and resulted in few treatment-related toxicities.
Elissa R Engel
Adrienne Hammill
Denise Adams
Roderic J Phillips
Michael Jeng
Megha M Tollefson
Ionela Iacobas
Deborah Schiff
Shoshana Greenberger
Michael Kelly
Ilona Frieden
Nibal Zaghloul
Beth Drolet
Amy Geddis
Dov Goldenberg
Kiersten Ricci
DOI: 10.1002/pbc.30215
Pediatric blood & cancer
2023 Apr
English
Analysis of Survival Differences Between Cutaneous and Subcutaneous Malignant Peripheral Nerve Sheath Tumors
Background: Malignant peripheral nerve sheath tumors (MPNSTs) are clinically aggressive soft tissue sarcomas that can present as cutaneous or subcutaneous based tumors that are commonly associated with neurofibromatosis type 1. Historically, these tumors have poor outcomes. Previously, no study has compared survival of cutaneous versus subcutaneous MPNSTs.
Objective: This study aims to investigate the difference in overall survival (OS) among cutaneous MPNSTs, subcutaneous MPNSTs of the head and neck, and subcutaneous MPNSTs of the trunk and extremities.
Materials and methods: Nine hundred eighteen patients were included in this retrospective study using the Surveillance, Epidemiology, and End-Results (SEER-9) database with primary cutaneous or subcutaneous MPNSTs from 1975 to 2016. OS was calculated using cox proportional hazard models for each group.
Results: No significant difference was revealed in OS between cutaneous or subcutaneous MPNSTs, regardless of location. Factors associated with decreased OS included advanced age, higher grade, and nondefinitive surgical modality.
Conclusion: This study results implies that unlike other soft tissue sarcomas, cutaneous presentation does not improve OS in patients with MPNSTs compared with their subcutaneous counterparts.
Courtney M Kromer
Nour Yacoub
David Xiong
Thomas Knackstedt
DOI: 10.1097/DSS.0000000000003717
Dermatologic surgery
2023 Apr 1
English
Primary care Providers' approaches to cervical cancer screening in Muslim females
The utilization of the Papanicolaou (Pap) test and the human papillomavirus (HPV) vaccine has significantly decreased rates of cervical cancer and related mortality. Disparities in receiving these preventive screenings are scarcely studied in Muslim females. Our study explores primary care providers' (PCP) approaches to cervical cancer screening in Muslim females. We created a cross-sectional Qualtrics survey using convenience sampling of PCPs who perform Pap tests in central Ohio. Recruitment emails were disseminated via departmental email listservs. We had 200 analyzable responses and 78% of respondents reported having Muslim patients. Bivariate analysis was used to identify predictors of providers' approaches. Providers younger than 35 years obtained a sexual history from Muslim females less frequently, family medicine providers were more likely to obtain a sexual history from Muslim females, and gynecologists were more likely to offer the HPV vaccine to Muslim females. Providers who counseled patients about Pap tests (P<0.001) and HPV modes of transmission (P<0.004) were more likely to offer cervical cancer screening for Muslim females. Our findings suggested that providers' age and specialty may be predictors of proactive cervical cancer screening and prevention in Muslim females and that there is a gap between current guidelines and preventive clinical practices regarding the HPV vaccine and transmission counseling.
Sondos Al Sad
Radhika Pandit
Nooralhuda Alhashim
Mahmoud Abdel-Rasoul
DOI: 10.1016/j.pmedr.2023.102126
Preventive medicine reports
2023 Feb 4
English
Cryo-EM structure of amyloid fibril formed by α-synuclein hereditary A53E mutation reveals a distinct protofilament interface
Synucleinopathies like Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple systems atrophy (MSA), have the same pathologic feature of misfolded α-synuclein protein (α-syn) accumulation in the brain. PD patients who carry α-syn hereditary mutations tend to have earlier onset and more severe clinical symptoms than sporadic PD patients. Therefore, revealing the effect of hereditary mutations to the α-syn fibril structure can help us understand these synucleinopathies' structural basis. Here, we present a 3.38 Å cryo-electron microscopy structure of α-synuclein fibrils containing the hereditary A53E mutation. The A53E fibril is symmetrically composed of two protofilaments, similar to other fibril structures of WT and mutant α-synuclein. The new structure is distinct from all other synuclein fibrils, not only at the interface between proto-filaments, but also between residues packed within the same proto-filament. A53E has the smallest interface with the least buried surface area among all α-syn fibrils, consisting of only two contacting residues. Within the same protofilament, A53E reveals distinct residue re-arrangement and structural variation at a cavity near its fibril core. Moreover, the A53E fibrils exhibit slower fibril formation and lower stability compared to WT and other mutants like A53T and H50Q, while also demonstrate strong cellular seeding in α-synuclein biosensor cells and primary neurons. In summary, our study aims to highlight structural differences - both within and between the protofilaments of A53E fibrils - and interpret fibril formation and cellular seeding of α-synuclein pathology in disease, which could further our understanding of the structure-activity relationship of α-synuclein mutants.
Chuanqi Sun
Kang Zhou
Peter DePaola 4th
Woo Shik Shin
Trae Hillyer
Michael R Sawaya
Ruowei Zhu
Chao Peng
Z Hong Zhou
Lin Jiang
DOI: 10.1016/j.jbc.2023.104566
The Journal of biological chemistry
2023 Apr
English
Obesity-related glomerulopathy in children: connecting pathophysiology to clinical care
Obesity has continued to emerge as a worldwide pandemic and has been associated with a significant increase in associated comorbidities. These include well-known conditions such as hypertension and diabetes, as well as lesser-known conditions such as obesity-related glomerulopathy (ORG). The main etiology of ORG is podocyte damage, but contributing theories include dysfunctional renin-angiotensin-aldosterone system activation, hyperinsulinemia and lipid deposition. Recent advances have made strides in understanding the complex pathophysiology of ORG. The key to treating ORG is weight loss and proteinuria reduction. Lifestyle modification, pharmacological interventions and surgery are mainstays of management. A special focus on obese children is required, as childhood obesity tracks into adulthood and primary prevention is key. In this review we discuss the pathogenesis, clinical features and established and newer treatment modalities of ORG.
Guneive Mangat
Nikhil Nair
Oren Barat
Brian Abboud
Priya Pais
Sumedha Bagga
Rupesh Raina
DOI: 10.1093/ckj/sfac233
Clinical kidney journal
2022 Oct 28
English
Surgical Intervention is Effective for the Treatment of Crohn's-related Rectovaginal Fistulas: Experience From a Tertiary Inflammatory Bowel Disease Practice
Background and aims: Rectovaginal fistula occurs in up to 10-20% of women with Crohn's disease, significantly affecting their quality of life. We sought to determine outcomes of single and repeat operative interventions.
Methods: A retrospective review of all adult patients with a Crohn's-related rectovaginal fistula, who underwent an operation between 1995 and 2021, was performed. Data collected included patient demographics, Crohn's-related medical treatment, surgical intervention, postoperative outcomes, and fistula outcomes.
Results: A total of 166 patients underwent 360 operations; mean age was 42.8 [+/-13.2] years; 34 [20.7%] patients were current and 58 [35.4%] former smokers. The most commonly performed procedure was: a local approach [n = 160, 44.5%] using fibrin glue, fistulotomy/fistulectomy, or seton placement; followed by a transvaginal/transanal approach [n = 113, 31.4%] with an advancement flap repair [including Martius advancement flap] and episoproctotomy; a transabdominal approach [n = 98, 27.2%] including proctectomy or re-do anastomosis; and finally gracilis muscle interposition [n = 8, 2.2%]. The median number of operative interventions per patient was 2 [1.0-3.0] procedures. The overall fistula healing rate per patient was 71.7% [n = 119] at a median follow-up of 5.5 [1.2-9.8] years. Factors that impaired healing included former smoking (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.31-0.87, p = 0.014) and seton insertion [OR 0.42, 95% CI 0.21-0.83, p = 0.012].
Conclusion: Over two-thirds of Crohn's-related rectovaginal fistulas can achieve closure with multiple surgical interventions. Smoking and seton usage negatively affect healing rates and should be avoided.
Ana M Otero-Piñeiro
Xue Jia
Karina E Pedersen
Tracy Hull
Jeremy Lipman
Stefan Holubar
Scott R Steele
Amy L Lightner
DOI: 10.1093/ecco-jcc/jjac151
Journal of Crohn's & colitis
2023 Apr 3
English
Increasing Primary Care Utilization of Medication-Assisted Treatment (MAT) for Opioid Use Disorder
Background: With increasing prevalence of opioid use disorders (OUDs) there is an urgent need for OUD trained front line primary care providers (PCPs) who can help improve patient adherence to addiction treatment. Unfortunately, most physicians have had limited training for treating patients with addiction, leaving clinicians under prepared. To address this need, we created a Medication-Assisted Treatment (MAT) training program specifically designed for PCPs.
Intervention: A 4-hour PCP focused buprenorphine office-based implementation training was designed to supplement the 8-hour SAMHSA DATA 2000 waiver training. The intent of the supplemental training is to increase PCP likelihood of implementing MAT through practical evidenced-based implementation, addressing barriers reported by waivered PCPs.
Methods: We developed and validated a new pre- and postsurvey instrument that assesses changes in participants knowledge, skills, and attitudes. Data were entered into REDCap, and composite scales were created and analyzed to determine pre-post differences.
Results: A total of 183 participants completed pre-post evaluations. Pre-post comparisons indicated substantial improvement in learner levels of confidence in implementing MAT care processes and in their interactions with MAT patients (df = 4, F = 203.518, P < .001). Participants described themselves as more comfortable identifying patients who would benefit from MAT (t = 15.04, P < .001), more competent in implementing MAT (t = 21.27, P < .001) and more willing (t = 15.56, P < .001) to implement MAT after training.
Conclusion: Evidence suggests that a new MAT training program that supplements the SAMHSA waiver training increases confidence and willingness to implement MAT among PCPs. Efforts to replicate this success to allow for further generalization and policy recommendations are warranted.
Stacey L Gardner-Buckshaw
Adam T Perzynski
Russell Spieth
Poojajeet Khaira
Chris Delos Reyes
Laura Novak
Denise Kropp
Aleece Caron
John M Boltri
DOI: 10.3122/jabfm.2022.220281R2
Journal of the American Board of Family Medicine
2023 Apr 3
English
Can the positive buffer the negative? Testing the impact of protective childhood experiences on adjustment in adults following trauma exposure
Background: It is unclear if protective childhood experiences (PCEs), like emotional support and economic stability, exert influence on adulthood adjustment. Prior research suggests PCEs can promote childhood resilience through increased social connection. In contrast, research has demonstrated potential life-long negative impacts of adverse childhood experiences (ACEs) on psychological health. This study examined the role of PCEs and ACEs in psychological symptoms following potentially traumatic events (PTE) in adults.
Methods: Participants (N = 128) were adults admitted to two Level 1 Trauma Centers following violence, motor-vehicle crashes, or other accidents. Participants reported childhood experiences and completed assessments of depression, PTSD, and social support at one, four, and nine months post-PTE.
Results: Structural Equation Modeling was used to simultaneously model PCEs and ACEs as predictors of psychological symptoms over time, with potential mediation through social support. PCEs overall did not directly affect psychological symptoms nor indirectly through social support. However, the emotional support component of PCEs had an indirect effect on psychological symptoms at baseline through social support. ACEs predicted greater psychological symptoms at baseline and over time.
Conclusion: PCEs consisting of childhood emotional support indirectly promote adjustment in adults after PTEs through initial social support, while ACEs exert direct effects on psychological symptoms.
Tam N M Nguyen
David J Disabato
John Gunstad
Douglas L Delahanty
Richard George
Farid Muakkassa
Ali F Mallat
Karin G Coifman
doi: 10.1080/10615806.2023.2193888. Online ahead of print.
Anxiety, stress, and coping
2023 Apr 3
English
My lifelong dedication to bile acid research
It is a great honor to be invited to write a reflections article on my scientific journey and lifelong bile acid research for the Journal of Biological Chemistry, in which I am proud to have published 24 articles. I have also published 21 articles in the Journal of Lipid Research, another journal of the American Society of Biochemistry and Molecular Biology. I begin my reflections from my early education in Taiwan, my coming to America for graduate study, and continue with my postdoctoral training in cytochrome P450 research, and my lifelong bile acid research career at Northeast Ohio Medical University. I have witnessed and helped in the transformation of this rural not so visible medical school to a well-funded leader in liver research. Writing this reflections article on my long and rewarding journey in bile acid research brings back many good memories. I am proud of my scientific contributions and attribute my academic success to hard work, perseverance, good mentoring, and networking. I hope these reflections of my academic career would help inspire young investigators to pursue an academic career in biochemistry and metabolic diseases.
John Y L Chiang
doi: 10.1016/j.jbc.2023.104672. Online ahead of print.
The Journal of Biological Chemistry
2023 Apr 3
English
Efficacy assessment of methylcellulose-based thermoresponsive hydrogels loaded with gallium acetylacetonate in osteoclastic bone resorption
Homeostatic imbalance involving progressive stimulation of osteoclast (OC) differentiation and function will lead to an increased risk of fragility fractures. In this regard, we investigated gallium acetylacetonate (GaAcAc) as a possible treatment for osteoclastic bone resorption. Further, the extent to which suitable delivery systems can enhance the therapeutic potential of GaAcAc was evaluated. GaAcAc solution (10-50 µg/mL) suppressed OC differentiation using murine monocytic RAW 264.7 or hematopoietic stem cells. Methylcellulose-based hydrogels were fabricated and characterized based on biocompatibility with bone cells, GaAcAc loading, and thermoresponsive behavior using storage (G') and loss (G″) moduli parameters. Compared to GaAcAc solution, hydrogels loaded with GaAcAc (GaMH) were more effective in suppressing OC differentiation and function. The number and extent of bone resorption pits from ex vivo studies were markedly reduced with GaMH treatment. Mechanistic assessment of GaMH efficacy showed superiority, compared to GaAcAc solution, in downregulating the expression of key markers involved in mediating OC differentiation (such as NFAT2, cFos, TRAF6, and TRAP) as well as in bone resorption by OCs (cathepsin K or CTSK). Additional studies (in vitro and in vivo) suggested that the performance of GaMH could be ascribed to controlled release of GaAcAc and the ability to achieve prolonged bio-retention after injection in BALB/c mice, which plausibly maximized the therapeutic impact of GaAcAc. Overall, the work demonstrated, for the first time, the therapeutic efficacy of GaAcAc and the therapeutic potential of GaMH delivery systems in osteoclastic bone resorption.
Pratyusha Ghanta
Timothy Winschel
Evin Hessel
Oluyinka Oyewumi
Tori Czech
Moses O Oyewumi
doi: 10.1007/s13346-023-01336-5. Online ahead of print.
Drug delivery and translational research
2023 Apr 4
English
Truth or Lies? The Pitfalls and Limitations of ChatGPT in Systematic Review Creation
Daniel Najafali
Justin M Camacho
Erik Reiche
Logan Galbraith
Shane D Morrison
Amir H Dorafshar
doi: 10.1093/asj/sjad093. Online ahead of print.
Aesthetic Surgery Journal
2023 Apr 5
English
Prolonged Time to Brake Following Lower Extremity Injuries
Introduction: No guidelines exist for recommending return to driving. This study will examine time to brake (TTB) after lower extremity injuries versus in uninjured people. The potential effect of various types of lower extremity injuries on TTB will be measured.
Methods: Patients with injuries to the pelvis, hip, femur, knee, tibia, ankle, and foot underwent testing using a driving simulator to assess TTB. Comparison was with a control group of uninjured people.
Results: Two-hundred thirty-two patients with lower extremity injuries participated. The majority were in the tibia and ankle regions (47%). Mean TTB for control subjects was 0.74 seconds, compared with 0.83 for injured patients, noting a 0.09-second difference (P = 0.017). Left-sided injuries averaged TTB of 0.80 seconds, right-sided injuries averaged TTB of 0.86 seconds, and bilateral injuries averaged TTB of 0.83 seconds, all prolonged versus control subjects. The longest TTB was exhibited after ankle and foot injuries (0.89 seconds) while the shortest was after tibial shaft fractures (0.76 seconds).
Discussion: Any lower extremity injury caused a prolonged TTB compared with control patients. Left, right, and bilateral injuries all had longer TTB. Ankle and foot injuries experienced the longest TTB. Additional investigation is warranted to develop safe guidelines for return to driving.
Andrew L Alejo
Alexander Rascoe
Chang-Yeon Kim
Bryan O Ren
Matthew T Hoffa
Isabella M Heimke
Heather A Vallier
DOI: 10.5435/JAAOSGlobal-D-23-00018
Journal of the American Academy of Orthopaedic Surgeons
2023 Apr 5
English
Relationship between hepatic and mitochondrial ceramides: a novel in vivo method to track ceramide synthesis
Ceramides (CERs) are key intermediate sphingolipids implicated in contributing to mitochondrial dysfunction and the development of multiple metabolic conditions. Despite the growing evidence of CER role in disease risk, kinetic methods to measure CER turnover are lacking, particularly using in vivo models. The utility of orally administered 13C3, 15N l-serine, dissolved in drinking water, was tested to quantify CER 18:1/16:0 synthesis in 10-week-old male and female C57Bl/6 mice. To generate isotopic labeling curves, animals consumed either a control diet or high-fat diet (HFD; n = 24/diet) for 2 weeks and varied in the duration of the consumption of serine-labeled water (0, 1, 2, 4, 7, or 12 days; n = 4 animals/day/diet). Unlabeled and labeled hepatic and mitochondrial CERs were quantified using liquid chromatography tandem MS. Total hepatic CER content did not differ between the two diet groups, whereas total mitochondrial CERs increased with HFD feeding (60%, P < 0.001). Within hepatic and mitochondrial pools, HFD induced greater saturated CER concentrations (P < 0.05) and significantly elevated absolute turnover of 16:0 mitochondrial CER (mitochondria: 59%, P < 0.001 vs. liver: 15%, P = 0.256). The data suggest cellular redistribution of CERs because of the HFD. These data demonstrate that a 2-week HFD alters the turnover and content of mitochondrial CERs. Given the growing data on CERs contributing to hepatic mitochondrial dysfunction and the progression of multiple metabolic diseases, this method may now be used to investigate how CER turnover is altered in these conditions.
Justine M Mucinski
Jonas M McCaffrey
R Scott Rector
Takhar Kasumov
Elizabeth J Parks
DOI: 10.1016/j.jlr.2023.100366
Journal of Lipid Research
2023 Apr 5
English
A scoping review of veterinary pharmacy education within US schools and colleges of pharmacy
Background: Pharmacists trained in veterinary pharmacy play important roles in community, hospital, academic, and industry settings. To date, there is limited available veterinary pharmacy education within Doctor of Pharmacy (PharmD) curricula. The objectives of this scoping review are to 1) assess available literature on veterinary pharmacy education with United States (US) schools and colleges of pharmacy and 2) identify gaps in which additional research in this area would benefit pharmacy educators and students.
Methods: A comprehensive literature search was conducted across four databases. Authors screened studies against relevant inclusion and exclusion criteria using a two-stage screening process.
Results: Sixteen studies met the inclusion criteria. Nine studies described veterinary pharmacy elective courses, three articles described related educational activities, and four articles focused on experiential education. Within the elective courses, the primary method of content delivery was via didactic lecture, but various active learning strategies were also employed, including live animal encounters and trips to compounding pharmacies and humane societies. Various assessment methods were used, and studies undertook Kirkpatrick level 1 and 2 evaluations.
Implications: Little literature describes or evaluates veterinary pharmacy education within US schools and colleges of pharmacy. Future research may investigate additional ways in which institutions teach and assess this content, especially pertaining to interprofessional and experiential education. Research determining which skills pertaining to veterinary pharmacy should be assessed and how those assessments should occur would also be beneficial.
Mary E Fredrickson
Natalie N Blaha
Maranda C Liogas
Alesandra M Sakacs
Madison Villers
Kimvan Bui
doi: 10.1016/j.cptl.2023.03.014. Online ahead of print.
Currents in Pharmacy Teaching & Learning
2023 Apr 5
English
Evaluating The Precocial-altricial Axis of Motor Skill at Birth in A Preterm Pig Model
The pace of locomotor development is a critical component of lifetime evolutionary fitness. Developmental researchers often divide species into two broad categories based on functional competence at birth: precocial infants who can independently stand and locomote soon after birth versus altricial infants who are either incapable of independent movement or can only do so in a rudimentary manner. However, investigating the lower level neuromotor and biomechanical traits that account for perinatal variation in motor development is complicated by the lack of experimental control inherent to all comparative analyses. Precocial and altricial animals often differ along a host of dimensions that can obfuscate the specific factors controlling motor development per se. Here, we propose an alternative approach of examining locomotor development in a nominally precocial species-the domestic pig (Sus scrofa)-in which gestation length has been experimentally manipulated, thereby creating "functionally altricial" cohorts for comparison. We used standard biomechanical testing to evaluate balance and locomotor performance in preterm pigs born at 94% full-term gestation (N = 29 individuals) and compared these data to a similar dataset on age-matched full-term piglets (N = 15 individuals). Static balance tests showed that preterm pigs were characterized by increased postural sway, particularly in the fore-aft (anteroposterior) direction. Locomotor analyses showed that preterm piglets tended to take shorter, more frequent strides, use higher duty factors, and preferentially choose gait patterns that ensured they were supported by at least three limbs during most of the stride cycle, though differences between preterm and full-term animals were often modulated by variation in locomotor speed. Morphometric analysis showed no differences in relative extensor muscle mass between preterm and full-term animals, suggesting that neurological immaturity might be more determinant of preterm piglet motor dysfunctions than musculoskeletal immaturity per se (though much work remains to be done to fully document the neuromotor phenotype of the preterm infant pig model). In many ways, the postural and locomotor deficits shown by the preterm piglets paralleled the locomotor phenotype of altricial mammals. Overall, our study demonstrates the utility of a "within-species" design for studying the biomechanical correlates and neuromotor basis of evolutionary variation in motor skill at birth.
Jesse W Young
Christopher J Mayerl
Alekhya Mannava
Claire Lewis
Tianhui Fan
Manas Nair
Christopher Mamone
Nicole M Schapker
Angela M Mossor
Rebecca Z German
doi: 10.1093/icb/icad013. Online ahead of print.
Integrative and Comparative Biology
2023 Apr 6
English
The Incidence of Postoperative Shoulder Stiffness After Arthroscopic Rotator Cuff Repair: A Systematic Review
Rotator cuff tear (RCT) is a common shoulder condition frequently treated with arthroscopic rotator cuff repair (ARCR) after conservative interventions have failed. Postoperative shoulder stiffness (POSS) is a common complication after ARCR. The purpose of this study is to determine the incidence of POSS after ARCR in total and based on tear extent prior to ARCR. A systematic review was performed using PubMed, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Medical Literature Analysis and Retrieval System Online (MEDLINE), and ScienceDirect databases. The search terms were "rotator cuff repair" AND "arthrofibrosis" OR "postoperative shoulder stiffness." Articles were selected based on ARCR and the presence of POSS documentation. Twenty-five articles out of 284 articles met the final selection criteria after reviewing for patients who received ARCR. Out of all patients (n=9,373), 597 had POSS (6.4%). Out of the 2,424 patients with a specified tear pattern, 96 out of 1,862 (5.2%) patients with full-thickness tears and 58 out of 562 (10.3%) patients with partial-thickness tears had POSS after ARCR. Partial-thickness tears are associated with higher rates of POSS after ARCR as compared to full-thickness tears (p<0.001). Overall, POSS is a common complication after ARCR with an incidence of 6.4%, regardless of tear type. POSS is more common in patients who receive ARCR for partial-thickness RCT (10.3%) as compared to patients who receive ARCR for full-thickness RCT (5.2%). More research is needed to determine other factors impacting the incidence of POSS after ARCR.
Anthony N Baumann
Caleb Oleson
Deven P Curtis
Thad Indermuhle
John Martin Leland 3rd
DOI: 10.7759/cureus.37199
The Cureus Journal of Medical Science
2023 Apr 6
English
Left atrial volume by cardiac CTA prior to catheter ablation: comparison to echocardiography and association with recurrent atrial fibrillation
Objective: Left atrial volume index (LAVI) by echocardiography can be challenging and its accuracy is highly dependent on image quality. Cardiac computed tomography angiography (CTA) can overcome echocardiographic LAVI measurement challenges; however, data are limited. Therefore, we evaluated the reproducibility of LAVI by CTA, its correlation to echocardiography, and its association with recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI) in this retrospective cohort study of patients who underwent CTA prior to PVI. LAVI was measured by CTA and echocardiography using the area length method.
Results: 74 patients had echocardiography and CTA within 6 months and were included in this study. The interobserver variability of LAVI measured by CTA was low (1.2%). CTA correlated with echocardiography but found larger LAVI values by a factor of 1.6. Also, LAVI cut off of ≥ 55 ml/m2 measured by CTA correlated with recurrent AF after PVI (adjusted Odds Ratio 3.47, p = 0.033).
Wissam Alajaji
Ottorino Costantini
Tyler L Taigen
Mark A Iler
DOI: 10.1186/s13104-023-06313-2
BMC Research Notes
2023 Apr 7
English
Avoidance Coping as a Vulnerability Factor for Negative Drinking Consequences Among Injury Survivors Experiencing PTSD Symptoms:An Ecological Momentary Assessment Study
The purpose of this study was to examine the dynamic relationships between daily PTSD symptom severity (PTSS), cognitive and behavioral avoidance coping, and negative drinking consequences following recent injury. Participants consisted of 36 injury survivors (Mage = 34.0, SD = 10.8; 75.0% male; 69.4% White) who completed thrice daily assessments of PTSS, avoidance coping, and negative drinking consequences for 7 days at 6-weeks post-injury. Although hypothesized relationships were not statistically significant in full models with covariates that included alcohol consumption, the confidence intervals associated with focal predictors provided support for predictions. Follow-up analyses without covariates indicated that on occasions when an injury survivor engaged in more avoidance coping and experienced higher levels of PTSS, negative drinking consequences increased by 9% (b = 0.02, SE = 0.01, p = .006). This interaction was primarily driven by cognitive avoidance coping (b = 0.03, SE = 0.01, p = .008). Routine screening of avoidance coping, PTSS, and alcohol consumption in the aftermath of recent injury might assist with identifying survivors at risk for negative drinking consequences. Interventions that address cognitive avoidance coping and drinking among survivors experiencing elevated PTSS may help to prevent the development of this comorbidity.
Bryce Hruska
Maria L Pacella-LaBarbara
Richard L George
Douglas L Delahanty
The purpose of this study was to examine the dynamic relationships between daily PTSD symptom severity (PTSS), cognitive and behavioral avoidance coping, and negative drinking consequences following recent injury. Participants consisted of 36 injury survivors (Mage = 34.0, SD = 10.8; 75.0% male; 69.4% White) who completed thrice daily assessments of PTSS, avoidance coping, and negative drinking consequences for 7 days at 6-weeks post-injury. Although hypothesized relationships were not statistically significant in full models with covariates that included alcohol consumption, the confidence intervals associated with focal predictors provided support for predictions. Follow-up analyses without covariates indicated that on occasions when an injury survivor engaged in more avoidance coping and experienced higher levels of PTSS, negative drinking consequences increased by 9% (b = 0.02, SE = 0.01, p = .006). This interaction was primarily driven by cognitive avoidance coping (b = 0.03, SE = 0.01, p = .008). Routine screening of avoidance coping, PTSS, and alcohol consumption in the aftermath of recent injury might assist with identifying survivors at risk for negative drinking consequences. Interventions that address cognitive avoidance coping and drinking among survivors experiencing elevated PTSS may help to prevent the development of this comorbidity.
Journal of Psychoactive Drugs
2023 Apr 9
English
Cognitive dysfunction and increased phosphorylated tau are associated with reduced O-GlcNAc signaling in an aging mouse model of metabolic syndrome
Metabolic syndrome (MetS), characterized by hyperglycemia, obesity, and hyperlipidemia, can increase the risk of developing late-onset dementia. Recent studies in patients and mouse models suggest a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism. Impaired glucose metabolism reduces glucose flux through the hexosamine metabolic pathway triggering attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification. The goal of the current study was to investigate the link between cognitive function, tau pathology, and O-GlcNAc signaling in an aging mouse model of MetS, agouti KKAy<sup>+/-</sup> . Male and female C57BL/6, non-agouti KKAy<sup>-/-</sup> , and agouti KKAy<sup>+/-</sup> mice were aged 12-18 months on standard chow diet. Body weight, blood glucose, total cholesterol, and triglyceride were measured to confirm the MetS phenotype. Cognition, sensorimotor function, and emotional reactivity were assessed for each genotype followed by plasma and brain tissue collection for biochemical and molecular analyses. Body weight, blood glucose, total cholesterol, and triglyceride levels were significantly elevated in agouti KKAy<sup>+/-</sup> mice versus C57BL/6 controls and non-agouti KKAy<sup>-/-</sup> . Behaviorally, agouti KKAy<sup>+/-</sup> revealed impairments in sensorimotor and cognitive function versus age-matched C57BL/6 and non-agouti KKAy<sup>-/-</sup> mice. Immunoblotting demonstrated increased phosphorylated tau accompanied with reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy<sup>+/-</sup> versus C57BL/6 control mice. Together, these data demonstrate that impaired cognitive function and AD-related pathology are associated with reduced O-GlcNAc signaling in aging MetS KKAy<sup>+/-</sup> mice. Overall, our study suggests that interaction of tau pathology with O-GlcNAc signaling may contribute to MetS-induced cognitive dysfunction in aging.
Shreya Gupta
Sanjay K A Jinka
Saugat Khanal
Neha Bhavnani
Fayez Almashhori
Jason Lallo
Amy Mathias
Yasmine Al-Rhayyel
Danielle Herman
John G Holden
Sheila M Fleming
Priya Raman
doi: 10.1002/jnr.25196. Online ahead of print.
Journal of Neuroscience Research
2023 Apr 9
English
Evaluating Demographic Data to Improve Confidence in Equity Analytics in a Children's Hospital
Healthcare institutions are placing greater emphasis on equitable care. To accurately track and validate equity metrics, Akron Children's Hospital evaluated how key fields are collected, analyzed, and visualized throughout the organization. Standardized recommendations in this area vary, and this investigation provided specific ways to advance analytics in this field. In addition, the technical infrastructure needed a comprehensive evaluation to increase confidence in using demographic data.
Methods: First, we reviewed how staff are trained to collect data at registration. Next, the electronic health record team standardized race and ethnicity fields with federal definitions. We found that fields were not consistently accessible across reporting tools. However, when present, all fields are sourced from the same electronic health record field. Finally, 6 months of encounters were analyzed and validated, with limitations to a seldom-populated Race 2 field.
Results: We compared data, including and excluding null values, to provide concise recommendations for standard visualizations. We uncovered many consistencies and a few inconsistencies that informed the next steps.
Conclusions: The results informed 7 recommendations to align Akron Children's Hospital's advancement in analytics for health equity data: standardize race and ethnicity fields across all reporting tools, add Child Opportunity Index 2.0 to the enterprise data warehouse, utilize data at the time of the patient's encounter, include null fields (patient refused, unknown, and not specified) in analysis, increase reporting capabilities for social determinants of health (SDOH), standardize multiracial data visualizations, and optimize reliable upstream data collection to increase reliability for all health equity measures.
Anna M Straus
Alissa Hayes
Jodi Simon
Andrea Sims
Karen Skerlong
Michele Wilmoth
Michael T Bigham
doi: 10.1097/pq9.0000000000000642
Pediatric Quality & Safety
2023 Apr 10
English
Intralesional Triamcinolone Acetonide Injection of Keloid Resulting in Copious Purulence
Sarah J Eley
Bryan T Carroll
doi: 10.1097/DSS.0000000000003795. Online ahead of print.
Dermatological Surgery
2023 Apr 11
English
Postanoxia-Induced Chorea Treated with Intravenous Fentanyl
The case presented is that of a young male with postanoxic brain injury secondary to cocaine overdose who began to exhibit choreiform movements of the left upper extremity. Traditional treatment options for chorea were unsuccessful, leading to the administration of fentanyl, which rapidly resolved the patient's choreiform movements. There is a limited research involving the treatment of chorea in anoxic brain injury as well as fentanyl's role in the movement pathway. We hypothesize that chorea can be caused or exacerbated by opioid withdrawal in a patient with chronic opioid use through modulation of dopamine transmission.
Ashley Audi
Brittany Cunningham
Christopher Newey
doi: 10.1155/2023/7652013
Case Reports in Neurological Medicine
2023 Apr 11
English
Gene Editing as the Future of Cardiac Amyloidosis Therapeutics
Background and significance: Cardiac Amyloidosis (CA) is a manifestation of a systemic disorder resulting from the deposition of the transthyretin (TTR) in the myocardium, resulting in a myriad manifestations ranging from conduction defects to heart failure. Several proteins, many of which have a genetic predisposition, are responsible for its presentation. Clustered Regularly Interspaced Short Palindromic Repeats of genetic information-Cas9 endonuclease (CRISPR-Cas9) is a RNA-guided endonuclease, which can be targeted using an RNA guide to specific locations in the genome. Until recently, CRISPR-Cas9 was studied in small animal models for its ability to decrease extracellular deposition and accumulation of amyloid in tissues.
Observations: Previously considered a rare disease, but recent advances in diagnostics and therapeutics have revealed the prevalence to be higher than estimated. There are two major classes of treatments for transthyretin cardiac amyloidosis (ATTR-CA): TTR stabilizers, such as tafamidis and AG10, and RNA interference (siRNA), such as patisiran and vutrisiran. Recently, gene editing has demonstrated some early clinical promise as an emerging therapeutic modality in the treatment of CA.
Conclusions and relevance: In an introductory gene editing human trial involving 12 subjects with TTR amyloidosis and amyloid cardiomyopathy (ATTR-CM), CRISPR-Cas9 therapy has demonstrated a reduction of approximately 90% of serum TTR proteins after 28 days. In this article, the authors review the current literature on therapeutic gene editing as a prospective curative treatment modality for cardiac amyloidosis.
Yashendra Sethi
Arun Umesh Mahtani
Nimrat Khehra
Inderbir Padda
Neil Patel
Sneha Annie Sebastian
Gurnaaz Malhi
Oroshay Kaiwan
Sunil Saith
Gurpreet Johal
doi: 10.1016/j.cpcardiol.2023.101741. Online ahead of print.
Current Problems in Cardiology
2023 Apr 12
English
Novel differential calcium regulation of hematopoietic stem and progenitor cells under physiological low oxygen conditions
Low oxygen bone marrow (BM) niches (~1%-4% low O<sub>2</sub> ) provide critical signals for hematopoietic stem/progenitor cells (HSC/HSPCs). Our presented data are the first to investigate live, sorted HSC/HSPCs in their native low O<sub>2</sub> conditions. Transcriptional and proteomic analysis uncovered differential Ca<sup>2+</sup> regulation that correlated with overlapping phenotypic populations consisting of robust increases of cytosolic and mitochondrial Ca<sup>2+</sup> , ABC transporter (ABCG2) expression and sodium/hydrogen exchanger (NHE1) expression in live, HSC/HSPCs remaining in constant low O<sub>2.</sub> We identified a novel Ca<sup>2+</sup> high population in HSPCs predominantly detected in low O<sub>2</sub> that displayed enhanced frequency of phenotypic LSK/LSKCD150 in low O<sub>2</sub> replating assays compared to Ca<sup>2+</sup> low populations. Inhibition of the Ca<sup>2+</sup> regulator NHE1 (Cariporide) resulted in attenuation of both the low O<sub>2</sub> induced Ca<sup>2+</sup> high population and subsequent enhanced maintenance of phenotypic LSK and LSKCD150 during low O<sub>2</sub> replating. These data reveal multiple levels of differential Ca<sup>2+</sup> regulation in low O<sub>2</sub> resulting in phenotypic, signaling, and functional consequences in HSC/HSPCs.
Paige Dausinas Ni
Melissa Hartman
Jacob Slack
Christopher Basile
Sheng Liu
Jun Wan
Heather A O'Leary
doi: 10.1002/jcp.30942. Online ahead of print.
Journal of Cell Physiology
2023 Apr 13
English
Pump the brakes! The hindlimbs of three-toed sloths decelerate and support suspensory locomotion
Modern tree sloths are one of few mammalian taxa for which quadrupedal suspension is obligatory. Sloth limb musculature is specialized for slow velocity, large force contractions that stabilize their body below branches and conserve energy during locomotion. However, it is unknown whether two- and three-toed sloths converge in their use of limb kinetics and if these patterns are comparable to how primates perform arboreal suspensory locomotion. This study addressed this need by collecting limb loading data in three-toed sloths (Bradypus variegatus; N=5) during suspensory walking. Sloths performed locomotor trials at their preferred speed on an instrumented beam apparatus with a force platform as the central supporting segment. Peak forces and impulses of the forelimb and hindlimb were recorded and analyzed in three dimensions. The hindlimbs of B. variegatus apply large braking forces greater in magnitude than peak forces generated by the forelimbs in propulsion, a pattern consistent with that observed in two-toed sloths. However, B. variegatus exhibits hindlimb-biased body weight support in vertical peak forces and impulse, with appreciable laterally directed forces in each limb pair, both of which vary from limb loading distributions in two-toed sloths. Moreover, body weight distribution between limb pairs is opposite to that employed by primates during quadrupedal suspension. Thus, there appear to be multiple strategies for achieving suspensory locomotion in arboreal mammals. These differences may be attributable to anatomical variation or phylogenetic position, but as of yet an explanation remains unknown. Future EMG analyses are expected to provide insight into how specific hindlimb muscle groups contribute to braking forces and stabilizing the center of mass of sloths during suspension.
Andrew J McKamy
Melody W Young
Angela M Mossor
Jesse W Young
Judy A Avey-Arroyo
Michael C Granatosky
Michael T Butcher
DOI: 10.1242/jeb.245622
The Journal of Experimental Biology
2023 April 15
English
"Why Won't They Believe Me?"
Mark R Munetz
Lois S Freedman
DOI: 10.1176/appi.ps.20230141
Psychiatric Services
2023 Apr 18
English
Principal neuron diversity in the murine lateral superior olive supports multiple sound localization strategies and segregation of information in higher processing centers
Principal neurons (PNs) of the lateral superior olive nucleus (LSO) in the brainstem of mammals compare information between the two ears and enable sound localization on the horizontal plane. The classical view of the LSO is that it extracts ongoing interaural level differences (ILDs). Although it has been known for some time that LSO PNs have intrinsic relative timing sensitivity, recent reports further challenge conventional thinking, suggesting the major function of the LSO is detection of interaural time differences (ITDs). LSO PNs include inhibitory (glycinergic) and excitatory (glutamatergic) neurons which differ in their projection patterns to higher processing centers. Despite these distinctions, intrinsic property differences between LSO PN types have not been explored. The intrinsic cellular properties of LSO PNs are fundamental to how they process and encode information, and ILD/ITD extraction places disparate demands on neuronal properties. Here we examine the ex vivo electrophysiology and cell morphology of inhibitory and excitatory LSO PNs in mice. Although overlapping, properties of inhibitory LSO PNs favor time coding functions while those of excitatory LSO PNs favor integrative level coding. Inhibitory and excitatory LSO PNs exhibit different activation thresholds, potentially providing further means to segregate information in higher processing centers. Near activation threshold, which may be physiologically similar to the sensitive transition point in sound source location for LSO, all LSO PNs exhibit single-spike onset responses that can provide optimal time encoding ability. As stimulus intensity increases, LSO PN firing patterns diverge into onset-burst cells, which can continue to encode timing effectively regardless of stimulus duration, and multi-spiking cells, which can provide robust individually integrable level information. This bimodal response pattern may produce a multi-functional LSO which can encode timing with maximum sensitivity and respond effectively to a wide range of sound durations and relative levels.
Hariprakash Haragopal
Bradley D Winters
DOI: 10.1038/s42003-023-04802-5
Communications Biology
2023 Apr 19
English
Facial Feminization Considerations for the Transgender Patient
Facial feminization is a desire expressed by certain individuals who identify beyond the gender binary seeking to align their physical appearance and the gender with which they identify. Although there are many ways to achieve a more feminine facial appearance, several factors influence routes that patients choose. This Viewpoint explores the considerations of physicians aiming to advocate for transgender patients, and “leverage expertise to promote protection of gender-affirming care” through medical and surgical interventions to achieve facial feminization. Due to gaps in literature, this Viewpoint further addresses some of the clinical, ethical, and aesthetic issues that require support of physicians.
Logan G Galbraith
Maya Schnall
Julie M Aultman
doi: 10.1097/GOX.0000000000004933
Plastic and Reconstructive Surgery
2023 Apr 19
English
Can Chatbots Assist with Grant Writing in Plastic Surgery? Utilizing ChatGPT to Start an R01 Grant
Daniel Najafali
Chandler Hinson
Justin M Camacho
Logan G Galbraith
Rohun Gupta
Chris M Reid
doi: 10.1093/asj/sjad116. Online ahead of print.
Anesthetic Surgery Journal
2023 Apr 21
English
Lower Extremity Reconstruction with Anterolateral Thigh Free-Flap Anastomoses: A Computational Fluid Dynamic Analysis
Background: The anterolateral thigh free flap is an option for repairing soft tissue defects of the distal lower extremity. This flap uses the descending branch of the lateral circumflex femoral (LCF) artery as the flap vessel. The recipient vessel in these flaps is often the anterior tibial (AT), posterior tibial (PT), or peroneal (P) arteries. Computational fluid dynamic (CFD) evaluation of anastomoses between these vessels can optimize outcomes.
Methods: Thirty-eight CFD models were created to model end-to-side (ETS) and end-to-end (ETE) anastomoses for lower extremity reconstruction. Seven out of thirty-eight models represented ETS anastomoses between the LCF and AT arteries with varying anastomotic angles. Nine out of thirty-eight models represented 45-degree ETS anastomoses between varying diameters of the LCF and AT, PT, and P arteries. Nine out of thirty-eight models represented stenosis on the flap vessel and recipient vessel, pre- and post-bifurcation. Nine out of thirty-eight models represented ETE anastomoses, rather than ETS, with varying vessel diameters. Four out of thirty-eight models represented ETE anastomoses with varying regions and levels of stenosis.
Results: Stasis of blood flow in ETS models increased as anastomotic angle increased in a logarithmic relationship (R 2 = 0.918). Flow was optimized overall as flap and recipient vessel diameters approached one another. In ETS models, flap vessel and postbifurcation recipient vessel stenosis were found to substantially increase stasis.
Conclusion: Selection of flap and recipient vessels with similar diameters can optimize outcomes in microvascular anastomoses. In the context of lower extremity reconstruction with the ALT flap, the PT artery can be recommended as a first-line recipient vessel due to its similar vessel caliber to the LCF and relative ease of surgical access compared with the P artery. Avoidance of areas of stenosis is recommended to ensure laminar flow and reduce the operative difficulty associated with performing anastomoses on nonpliable arteries. Striving for increased acuity of anastomotic angles is recommended to optimize the flow in ETS microvascular anastomoses.
Sanjay K A Jinka
Ashoka G K Jinka
Jeffrey E Janis
doi: 10.1055/a-2056-0629. Online ahead of print.
Journal of Reconstructive Microsurgery
2023 Apr 24
English