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Full-Text Articles in Medicine and Health Sciences

Hormonal Basis Of Sex Differences In Anesthetic Sensitivity, Andrzej Z Wasilczuk, Cole Rinehart, Adeeti Aggarwal, Martha E Stone, George A Mashour, Michael S Avidan, Max B Kelz, Alex Proekt, Reccognition Study Group Jan 2024

Hormonal Basis Of Sex Differences In Anesthetic Sensitivity, Andrzej Z Wasilczuk, Cole Rinehart, Adeeti Aggarwal, Martha E Stone, George A Mashour, Michael S Avidan, Max B Kelz, Alex Proekt, Reccognition Study Group

2020-Current year OA Pubs

General anesthesia-a pharmacologically induced reversible state of unconsciousness-enables millions of life-saving procedures. Anesthetics induce unconsciousness in part by impinging upon sexually dimorphic and hormonally sensitive hypothalamic circuits regulating sleep and wakefulness. Thus, we hypothesized that anesthetic sensitivity should be sex-dependent and modulated by sex hormones. Using distinct behavioral measures, we show that at identical brain anesthetic concentrations, female mice are more resistant to volatile anesthetics than males. Anesthetic sensitivity is bidirectionally modulated by testosterone. Castration increases anesthetic resistance. Conversely, testosterone administration acutely increases anesthetic sensitivity. Conversion of testosterone to estradiol by aromatase is partially responsible for this effect. In contrast, …


Postprandial Glucose Variability Following Typical Meals In Youth Living With Type 1 Diabetes., Susana R. Patton, Simon Bergford, Jennifer L. Sherr, Robin L. Gal, Peter Calhoun, Mark A. Clements, Michael C. Riddell, Corby K. Martin Jan 2024

Postprandial Glucose Variability Following Typical Meals In Youth Living With Type 1 Diabetes., Susana R. Patton, Simon Bergford, Jennifer L. Sherr, Robin L. Gal, Peter Calhoun, Mark A. Clements, Michael C. Riddell, Corby K. Martin

Manuscripts, Articles, Book Chapters and Other Papers

We explored the association between macronutrient intake and postprandial glucose variability in a large sample of youth living with T1D and consuming free-living meals. In the Type 1 Diabetes Exercise Initiative Pediatric (T1DEXIP) Study, youth took photographs before and after their meals on 3 days during a 10 day observation period. We used the remote food photograph method to obtain the macronutrient content of youth's meals. We also collected physical activity, continuous glucose monitoring, and insulin use data. We measured glycemic variability using standard deviation (SD) and coefficient of variation (CV) of glucose for up to 3 h after meals. …


Sarm1 Knockout Prevents Type 1 Diabetic Bone Disease In Females Independent Of Neuropathy, Jennifer M. Brazill, Ivana R. Shen, Clarissa S. Craft, Kristann L. Magee, Jay S. Park, Madelyn Lorenz, Amy Strickland, Natalie K. Wee, Xiao Zhang, Alec T. Beeve, Gretchen A. Meyer, Jeffrey Milbrandt, Aaron Diantonio, Erica L. Scheller Jan 2024

Sarm1 Knockout Prevents Type 1 Diabetic Bone Disease In Females Independent Of Neuropathy, Jennifer M. Brazill, Ivana R. Shen, Clarissa S. Craft, Kristann L. Magee, Jay S. Park, Madelyn Lorenz, Amy Strickland, Natalie K. Wee, Xiao Zhang, Alec T. Beeve, Gretchen A. Meyer, Jeffrey Milbrandt, Aaron Diantonio, Erica L. Scheller

2020-Current year OA Pubs

Patients with diabetes have a high risk of developing skeletal diseases accompanied by diabetic peripheral neuropathy (DPN). In this study, we isolated the role of DPN in skeletal disease with global and conditional knockout models of sterile-α and TIR-motif-containing protein-1 (Sarm1). SARM1, an NADase highly expressed in the nervous system, regulates axon degeneration upon a range of insults, including DPN. Global knockout of Sarm1 prevented DPN, but not skeletal disease, in male mice with type 1 diabetes (T1D). Female wild-type mice also developed diabetic bone disease but without DPN. Unexpectedly, global Sarm1 knockout completely protected female mice from T1D-associated bone …


Implementation And Outcomes Of A Pilot Collaborative Surgical Hydrocele Training In Côte D'Ivoire, Kevin Montes, Georgina Angoa, Catherine M Bjerum, Adama Guira, Olivier K Kouadio, Allassane F Ouattara, Gary J Weil, Peter U Fischer, Aboulaye Meite, Benjamin G Koudou, Philip J Budge Jan 2024

Implementation And Outcomes Of A Pilot Collaborative Surgical Hydrocele Training In Côte D'Ivoire, Kevin Montes, Georgina Angoa, Catherine M Bjerum, Adama Guira, Olivier K Kouadio, Allassane F Ouattara, Gary J Weil, Peter U Fischer, Aboulaye Meite, Benjamin G Koudou, Philip J Budge

2020-Current year OA Pubs

Lymphatic filariasis (LF) is a neglected tropical disease that can cause hydrocele and its associated stigma, loss of economic productivity, and depression. Hydrocele surgery is an essential part of LF morbidity management but can be difficult for national programs to implement. To improve access to hydrocele surgeries in Côte d'Ivoire, we provided a WHO-certified surgical training for six surgical teams from five health districts in Côte d'Ivoire. We then evaluated the surgical outcomes and assessed the impact of hydrocele surgery on quality of life of hydrocelectomy patients. Preoperative and operative records were reviewed to describe baseline hydrocele characteristics and operative …


Implications Of Preoperative Depression For Lumbar Spine Surgery Outcomes: A Systematic Review And Meta-Analysis, Saad Javeed, Braeden Benedict, Salim Yakdan, Samia Saleem, Justin K Zhang, Kathleen Botterbush, Madelyn R Frumkin, Angela Hardi, Brian Neuman, Jay F Piccirillo, Burel R Goodin, Thomas L Rodebaugh, Wilson Z Ray, Jacob K Greenberg, Et Al. Jan 2024

Implications Of Preoperative Depression For Lumbar Spine Surgery Outcomes: A Systematic Review And Meta-Analysis, Saad Javeed, Braeden Benedict, Salim Yakdan, Samia Saleem, Justin K Zhang, Kathleen Botterbush, Madelyn R Frumkin, Angela Hardi, Brian Neuman, Jay F Piccirillo, Burel R Goodin, Thomas L Rodebaugh, Wilson Z Ray, Jacob K Greenberg, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Comorbid depression is common among patients with degenerative lumbar spine disease. Although a well-researched topic, the evidence of the role of depression in spine surgery outcomes remains inconclusive.

OBJECTIVE: To investigate the association between preoperative depression and patient-reported outcome measures (PROMs) after lumbar spine surgery.

DATA SOURCES: A systematic search of PubMed, Cochrane Database of Systematic Reviews, Embase, Scopus, PsychInfo, Web of Science, and ClinicalTrials.gov was performed from database inception to September 14, 2023.

STUDY SELECTION: Included studies involved adults undergoing lumbar spine surgery and compared PROMs in patients with vs those without depression. Studies evaluating the correlation between …


A Dataset Of Digital Holograms Of Normal And Thalassemic Cells, Vahid Abbasian, Arash Darafsheh Jan 2024

A Dataset Of Digital Holograms Of Normal And Thalassemic Cells, Vahid Abbasian, Arash Darafsheh

2020-Current year OA Pubs

Digital holographic microscopy (DHM) is an intriguing medical diagnostic tool due to its label-free and quantitative nature, providing high-contrast images of phase samples. By capturing both intensity and phase information, DHM enables the numerical reconstruction of quantitative phase images. However, the lateral resolution is limited by the diffraction limit, which prompted the recent suggestion of microsphere-assisted DHM to enhance the DHM resolution straightforwardly. The use of such a technique as a medical diagnostic tool requires testing and validation of the proposed assays to prove their feasibility and viability. This paper publishes 760 and 609 microsphere-assisted DHM images of normal and …


Short-Stay Units Vs Routine Admission From The Emergency Department In Patients With Acute Heart Failure: The Ssu-Ahf Randomized Clinical Trial, Peter S Pang, Douglas Char, Et Al. Jan 2024

Short-Stay Units Vs Routine Admission From The Emergency Department In Patients With Acute Heart Failure: The Ssu-Ahf Randomized Clinical Trial, Peter S Pang, Douglas Char, Et Al.

2020-Current year OA Pubs

IMPORTANCE: More than 80% of patients who present to the emergency department (ED) with acute heart failure (AHF) are hospitalized. With more than 1 million annual hospitalizations for AHF in the US, safe and effective alternatives are needed. Care for AHF in short-stay units (SSUs) may be safe and more efficient than hospitalization, especially for lower-risk patients, but randomized clinical trial data are lacking.

OBJECTIVE: To compare the effectiveness of SSU care vs hospitalization in lower-risk patients with AHF.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial randomly assigned low-risk patients with AHF 1:1 to SSU or hospital admission …


Organ Preservation And Survival By Clinical Response Grade In Patients With Rectal Cancer Treated With Total Neoadjuvant Therapy: A Secondary Analysis Of The Opra Randomized Clinical Trial, Hannah M Thompson, Steven R Hunt, Et Al. Jan 2024

Organ Preservation And Survival By Clinical Response Grade In Patients With Rectal Cancer Treated With Total Neoadjuvant Therapy: A Secondary Analysis Of The Opra Randomized Clinical Trial, Hannah M Thompson, Steven R Hunt, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Assessing clinical tumor response following completion of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer is paramount to select patients for watch-and-wait treatment.

OBJECTIVE: To assess organ preservation (OP) and oncologic outcomes according to clinical tumor response grade.

DESIGN, SETTING, AND PARTICIPANTS: This was secondary analysis of the Organ Preservation in Patients with Rectal Adenocarcinoma trial, a phase 2, nonblinded, multicenter, randomized clinical trial. Randomization occurred between April 2014 and March 2020. Eligible participants included patients with stage II or III rectal adenocarcinoma. Data analysis occurred from March 2022 to July 2023.

INTERVENTION: Patients were randomized …


Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal Jan 2024

Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Prostate apoptosis response-4 (Par-4) tumor suppressor protein has gained attention as a potential therapeutic target owing to its unique ability to selectively induce apoptosis in cancer cells, sensitize them to chemotherapy and radiotherapy, and mitigate drug resistance. It has recently been reported that Par-4 interacts synergistically with cisplatin, a widely used anticancer drug. However, the mechanistic details underlying this relationship remain elusive. In this investigation, we employed an array of biophysical techniques, including circular dichroism spectroscopy, dynamic light scattering, and UV–vis absorption spectroscopy, to characterize the interaction between the active caspase-cleaved Par-4 (cl-Par-4) fragment and cisplatin. Additionally, elemental analysis was …


Digital Clock Drawing As An Alzheimer's Disease Susceptibility Biomarker: Associations With Genetic Risk Score And Apoe In Older Adults, L I Thompson, M Cummings, S Emrani, David J. Libon, A Ang, C Karjadi, R Au, C Liu Jan 2024

Digital Clock Drawing As An Alzheimer's Disease Susceptibility Biomarker: Associations With Genetic Risk Score And Apoe In Older Adults, L I Thompson, M Cummings, S Emrani, David J. Libon, A Ang, C Karjadi, R Au, C Liu

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia in older adults, but most people are not diagnosed until significant neuronal loss has likely occurred along with a decline in cognition. Non-invasive and cost-effective digital biomarkers for AD have the potential to improve early detection.

OBJECTIVE: We examined the validity of DCTclockTM (a digitized clock drawing task) as an AD susceptibility biomarker.

DESIGN: We used two primary independent variables, Apolipoprotein E (APOE) ε4 allele carrier status and polygenic risk score (PRS). We examined APOE and PRS associations with DCTclockTM composite scores as dependent measures.

SETTING: We used existing data …


A Global Multicohort Study To Map Subcortical Brain Development And Cognition In Infancy And Early Childhood, Ann M Alex, Kelly Botteron, Et Al. Jan 2024

A Global Multicohort Study To Map Subcortical Brain Development And Cognition In Infancy And Early Childhood, Ann M Alex, Kelly Botteron, Et Al.

2020-Current year OA Pubs

The human brain grows quickly during infancy and early childhood, but factors influencing brain maturation in this period remain poorly understood. To address this gap, we harmonized data from eight diverse cohorts, creating one of the largest pediatric neuroimaging datasets to date focused on birth to 6 years of age. We mapped the developmental trajectory of intracranial and subcortical volumes in ∼2,000 children and studied how sociodemographic factors and adverse birth outcomes influence brain structure and cognition. The amygdala was the first subcortical volume to mature, whereas the thalamus exhibited protracted development. Males had larger brain volumes than females, and …


Responsive Neurostimulation For People With Drug-Resistant Epilepsy And Autism Spectrum Disorder, Madeline C. Fields, Emily A. Johnson, John Zempel, Et Al. Jan 2024

Responsive Neurostimulation For People With Drug-Resistant Epilepsy And Autism Spectrum Disorder, Madeline C. Fields, Emily A. Johnson, John Zempel, Et Al.

2020-Current year OA Pubs

PURPOSE: Individuals with autism spectrum disorder (ASD) have comorbid epilepsy at much higher rates than the general population, and about 30% will be refractory to medication. Patients with drug-resistant epilepsy (DRE) should be referred for surgical evaluation, yet many with ASD and DRE are not resective surgical candidates. The aim of this study was to examine the response of this population to the responsive neurostimulator (RNS) System.

METHODS: This multicenter study evaluated patients with ASD and DRE who underwent RNS System placement. Patients were included if they had the RNS System placed for 1 year or more. Seizure reduction and …


Leveraging Mhealth To Mitigate The Impact Of Covid-19 In Black American Communities: Qualitative Analysis, Kelly M Harris, Tilicia Mayo Gamble, Madelyn G Yoo, Lindsay A Spell, Timira N Minor, Holly Jones, Donald Lynch Dec 2023

Leveraging Mhealth To Mitigate The Impact Of Covid-19 In Black American Communities: Qualitative Analysis, Kelly M Harris, Tilicia Mayo Gamble, Madelyn G Yoo, Lindsay A Spell, Timira N Minor, Holly Jones, Donald Lynch

2020-Current year OA Pubs

BACKGROUND: COVID-19 remains an ongoing public health crisis. Black Americans remain underrepresented among those vaccinated and overrepresented in both COVID-19 morbidity and mortality. Medical misinformation, specifically related to COVID-19, has exacerbated the impact of the disease in Black American communities. Communication tools and strategies to build relationships and disseminate credible and trustworthy diagnostic and preventative health information are necessary to improve outcomes and equity for historically oppressed populations.

OBJECTIVE: As the initial phase of a larger mixed methods project to develop, pilot, and evaluate a mobile health (mHealth) intervention among a population at high risk for COVID-19 and cardiovascular comorbidities, …


Dsm-5 Conduct Disorder And Symptoms In Youths At High Risk Of Psychosis In Kenya With Dsm-5 Mental Disorders And Substance Use: Towards Integrated Management, David M Ndetei, Victoria Mutiso, Christine Musyimi, Reinpeter Momanyi, Pascalyne Nyamai, Peter Tyrer, Daniel Mamah Dec 2023

Dsm-5 Conduct Disorder And Symptoms In Youths At High Risk Of Psychosis In Kenya With Dsm-5 Mental Disorders And Substance Use: Towards Integrated Management, David M Ndetei, Victoria Mutiso, Christine Musyimi, Reinpeter Momanyi, Pascalyne Nyamai, Peter Tyrer, Daniel Mamah

2020-Current year OA Pubs

Little is known about the prevalence of Conduct Disorder (CD) and symptoms of CD in high risk psychosis persons at both clinical and community populations in LMICs and in particular Kenya. This study aimed to document (1) the prevalence of CD diagnosis and symptoms in youth who screened positive for psychosis and (2) the associated mental disorders and substance use in the same cohort in LMIC. The sample size was 536 students who had screened positive on the Washington Early Recognition Center Affectivity and Psychosis (WERCAP) from a population of 9,742 high school, college and university students, but had not …


Mental Health Differences In Medical Students Based On Curriculum And Gender, Maxim Jestin, Shelly Sharma, Deval Jhaveri, Brittany Mitchell, Dean Micciche, Venkat Venkataraman, Kathryn Lambert Dec 2023

Mental Health Differences In Medical Students Based On Curriculum And Gender, Maxim Jestin, Shelly Sharma, Deval Jhaveri, Brittany Mitchell, Dean Micciche, Venkat Venkataraman, Kathryn Lambert

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: The prevalence of mental health struggles among students in medical school is widely reported; however, little is known about how it is impacted by the medical school curriculum. This study aimed to evaluate differences in anxiety, depression, and emotional exhaustion in medical students based on gender, class year, and curriculum.

METHODS: An anonymous online survey consisting of questions from established, validated questionnaires about demographics, anxiety, depression, emotional exhaustion, and personal health behaviors was sent to 817 medical students who attended Rowan-Virtua School of Osteopathic Medicine during the Spring of 2021. When applying to this school, each of these students …


Nucleus Accumbens Core Single Cell Ensembles Bidirectionally Respond To Experienced Versus Observed Aversive Events, Oyku Dinckol, Noah Harris Wenger, Jennifer E Zachry, Munir Gunes Kutlu Dec 2023

Nucleus Accumbens Core Single Cell Ensembles Bidirectionally Respond To Experienced Versus Observed Aversive Events, Oyku Dinckol, Noah Harris Wenger, Jennifer E Zachry, Munir Gunes Kutlu

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Fear learning is a critical feature of survival skills among mammals. In rodents, fear learning manifests itself through direct experience of the aversive event or social transmission of aversive stimuli such as observing and acting on conspecifics' distress. The neuronal network underlying the social transmission of information largely overlaps with the brain regions that mediate behavioral responses to aversive and rewarding stimuli. In this study, we recorded single cell activity patterns of nucleus accumbens (NAc) core neurons using in vivo optical imaging of calcium transients via miniature scopes. This cutting-edge imaging methodology not only allows us to record activity patterns …


Master Transcription Factor Reprogramming Unleashes Selective Translation Promoting Castration Resistance And Immune Evasion In Lethal Prostate Cancer, Sandra Santasusagna, Shijia Zhu, Vijayakumar Jawalagatti, Marc Carceles-Cordon, Adam Ertel, Saioa Garcia-Longarte, Won-Min Song, Naoto Fujiwara, Peiyao Li, Isabel Mendizabal, Daniel P. Petrylak, William Kevin Kelly, E. Premkumar Reddy, Liguo Wang, Matthew J. Schiewer, Amaia Lujambio, Jeffrey Karnes, Karen E. Knudsen, Carlos Cordon-Cardo, Haidong Dong, Haojie Huang, Arkaitz Carracedo, Yujin Hoshida, Veronica Rodriguez-Bravo, Josep Domingo-Domenech Dec 2023

Master Transcription Factor Reprogramming Unleashes Selective Translation Promoting Castration Resistance And Immune Evasion In Lethal Prostate Cancer, Sandra Santasusagna, Shijia Zhu, Vijayakumar Jawalagatti, Marc Carceles-Cordon, Adam Ertel, Saioa Garcia-Longarte, Won-Min Song, Naoto Fujiwara, Peiyao Li, Isabel Mendizabal, Daniel P. Petrylak, William Kevin Kelly, E. Premkumar Reddy, Liguo Wang, Matthew J. Schiewer, Amaia Lujambio, Jeffrey Karnes, Karen E. Knudsen, Carlos Cordon-Cardo, Haidong Dong, Haojie Huang, Arkaitz Carracedo, Yujin Hoshida, Veronica Rodriguez-Bravo, Josep Domingo-Domenech

Department of Medical Oncology Faculty Papers

Signaling rewiring allows tumors to survive therapy. Here we show that the decrease of the master regulator microphthalmia transcription factor (MITF) in lethal prostate cancer unleashes eukaryotic initiation factor 3B (eIF3B)-dependent translation reprogramming of key mRNAs conferring resistance to androgen deprivation therapy (ADT) and promoting immune evasion. Mechanistically, MITF represses through direct promoter binding eIF3B, which in turn regulates the translation of specific mRNAs. Genome-wide eIF3B enhanced cross-linking immunoprecipitation sequencing (eCLIP-seq) showed specialized binding to a UC-rich motif present in subsets of 5' untranslated regions. Indeed, translation of the androgen receptor and major histocompatibility complex I (MHC-I) through this motif …


Overall Survival Of Patients With Chl Who Progress After Autologous Stem Cell Transplant: Results In The Novel Agent Era, Sanjal H Desai, Brad Kahl, Raya Saba, Et Al. Dec 2023

Overall Survival Of Patients With Chl Who Progress After Autologous Stem Cell Transplant: Results In The Novel Agent Era, Sanjal H Desai, Brad Kahl, Raya Saba, Et Al.

2020-Current year OA Pubs

In the pre-novel agent era, the median postprogression overall survival (PPS) of patients with classic Hodgkin lymphoma (cHL) who progress after autologous stem cell transplant (ASCT) was 2 to 3 years. Recently, checkpoint inhibitors (CPI) and brentuximab vedotin (BV) have improved the depth and durability of response in this population. Here, we report the estimate of PPS in patients with relapsed cHL after ASCT in the era of CPI and BV. In this multicenter retrospective study of 15 participating institutions, adult patients with relapsed cHL after ASCT were included. Study objective was postprogression overall survival (PPS), defined as the time …


A Multilevel Mhealth Intervention Boosts Adherence To Hydroxyurea In Individuals With Sickle Cell Disease, Jane S Hankins, Allison A King, Ana A Baumann, Lisa M Klesges, Et Al. Dec 2023

A Multilevel Mhealth Intervention Boosts Adherence To Hydroxyurea In Individuals With Sickle Cell Disease, Jane S Hankins, Allison A King, Ana A Baumann, Lisa M Klesges, Et Al.

2020-Current year OA Pubs

Hydroxyurea reduces sickle cell disease (SCD) complications, but medication adherence is low. We tested 2 mobile health (mHealth) interventions targeting determinants of low adherence among patients (InCharge Health) and low prescribing among providers (HU Toolbox) in a multi-center, non-randomized trial of individuals with SCD ages 15-45. We compared the percentage of days covered (PDC), labs, healthcare utilization, and self-reported pain over 24 weeks of intervention and 12 weeks post-study with a 24-week preintervention interval. We enrolled 293 patients (51% male; median age 27.5 years, 86.8% HbSS/HbSβ0-thalassemia). The mean change in PDC among 235 evaluable subjects increased (39.7% to 56.0%; P < 0.001) and sustained (39.7% to 51.4%, P < 0.001). Mean HbF increased (10.95% to 12.78%; P = 0.03). Self-reported pain frequency reduced (3.54 to 3.35 events/year; P = 0.041). InCharge Health was used ≥1 day by 199 of 235 participants (84.7% implementation; median usage: 17% study days; IQR: 4.8-45.8%). For individuals with ≥1 baseline admission for pain, admissions per 24 weeks declined from baseline through 24 weeks (1.97 to 1.48 events/patient, P = 0.0045) and weeks 25-36 (1.25 events/patient, P = 0.0015). PDC increased with app use (P < 0.001), with the greatest effect in those with private insurance (P = 0.0078), older subjects (P = 0.033), and those with lower pain interference (P = 0.0012). Of the 89 providers (49 hematologists, 36 advanced care providers, 4 unreported), only 11.2% used HU Toolbox ≥1/month on average. This use did not affect change in PDC. Tailoring mHealth solutions to address barriers to hydroxyurea adherence can potentially improve adherence and provide clinical benefits. A definitive randomized study is warranted. This trial was registered at www.clinicaltrials.gov as #NCT04080167.


Design And Structural Validation Of Peptide-Drug Conjugate Ligands Of The Kappa-Opioid Receptor, Edin Muratspahić, Jianming Han, Balazs R Varga, Kevin Appourchaux, Susruta Majumdar, Tao Che, Et Al. Dec 2023

Design And Structural Validation Of Peptide-Drug Conjugate Ligands Of The Kappa-Opioid Receptor, Edin Muratspahić, Jianming Han, Balazs R Varga, Kevin Appourchaux, Susruta Majumdar, Tao Che, Et Al.

2020-Current year OA Pubs

Despite the increasing number of GPCR structures and recent advances in peptide design, the development of efficient technologies allowing rational design of high-affinity peptide ligands for single GPCRs remains an unmet challenge. Here, we develop a computational approach for designing conjugates of lariat-shaped macrocyclized peptides and a small molecule opioid ligand. We demonstrate its feasibility by discovering chemical scaffolds for the kappa-opioid receptor (KOR) with desired pharmacological activities. The designed De Novo Cyclic Peptide (DNCP)-β-naloxamine (NalA) exhibit in vitro potent mixed KOR agonism/mu-opioid receptor (MOR) antagonism, nanomolar binding affinity, selectivity, and efficacy bias at KOR. Proof-of-concept in vivo efficacy studies …


Trends In Ductus Arteriosus Stent Versus Blalock-Taussig-Thomas Shunt Use And Comparison Of Cost, Length Of Stay, And Short-Term Outcomes In Neonates With Ductal-Dependent Pulmonary Blood Flow: An Observational Study Using The Pediatric Health Information Systems Database, Bethan A Lemley, Lezhou Wu, Amy L Roberts, Russell T Shinohara, William O Quarshie, Athar M Qureshi, Christopher L Smith, Yoav Dori, Matthew J Gillespie, Jonathan J Rome, Andrew C Glatz, Sandra Amaral, Michael L O'Byrne Dec 2023

Trends In Ductus Arteriosus Stent Versus Blalock-Taussig-Thomas Shunt Use And Comparison Of Cost, Length Of Stay, And Short-Term Outcomes In Neonates With Ductal-Dependent Pulmonary Blood Flow: An Observational Study Using The Pediatric Health Information Systems Database, Bethan A Lemley, Lezhou Wu, Amy L Roberts, Russell T Shinohara, William O Quarshie, Athar M Qureshi, Christopher L Smith, Yoav Dori, Matthew J Gillespie, Jonathan J Rome, Andrew C Glatz, Sandra Amaral, Michael L O'Byrne

2020-Current year OA Pubs

BACKGROUND: The modified Blalock-Taussig-Thomas shunt is the gold standard palliation for securing pulmonary blood flow in infants with ductal-dependent pulmonary blood flow. Recently, the ductus arteriosus stent (DAS) has become a viable alternative.

METHODS AND RESULTS: This was a retrospective multicenter study of neonates ≤30 days undergoing DAS or Blalock-Taussig-Thomas shunt placement between January 1, 2017 and December 31, 2020 at hospitals reporting to the Pediatric Health Information Systems database. We performed generalized linear mixed-effects modeling to evaluate trends in intervention and intercenter variation, propensity score adjustment and inverse probability weighting with linear mixed-effects modeling to analyze length of stay …


Recombinant Human Perlecan Dv And Its Lg3 Subdomain Are Neuroprotective And Acutely Functionally Restorative In Severe Experimental Ischemic Stroke, Ifechukwude Joachim Biose, Ibolya Rutkai, Bryan Clossen, Gary Gage, Kenneth Schechtman, H Davis Adkisson 4th, Gregory J Bix Dec 2023

Recombinant Human Perlecan Dv And Its Lg3 Subdomain Are Neuroprotective And Acutely Functionally Restorative In Severe Experimental Ischemic Stroke, Ifechukwude Joachim Biose, Ibolya Rutkai, Bryan Clossen, Gary Gage, Kenneth Schechtman, H Davis Adkisson 4th, Gregory J Bix

2020-Current year OA Pubs

Despite recent therapeutic advancements, ischemic stroke remains a major cause of death and disability. It has been previously demonstrated that  ~ 85-kDa recombinant human perlecan domain V (rhPDV) binds to upregulated integrin receptors (α2β1 and α5β1) associated with neuroprotective and functional improvements in various animal models of acute ischemic stroke. Recombinant human perlecan laminin-like globular domain 3 (rhPDV


Survival Of Veterans Treated With Enzalutamide And Abiraterone For Metastatic Castrate Resistant Prostate Cancer Based On Comorbid Diseases, Martin W Schoen, Kenneth R Carson, Seth A Eisen, Charles L Bennett, Suhong Luo, Melissa A Reimers, Eric M Knoche, Alison L Whitmer, Yan Yan, Bettina F Drake, Kristen M Sanfilippo Dec 2023

Survival Of Veterans Treated With Enzalutamide And Abiraterone For Metastatic Castrate Resistant Prostate Cancer Based On Comorbid Diseases, Martin W Schoen, Kenneth R Carson, Seth A Eisen, Charles L Bennett, Suhong Luo, Melissa A Reimers, Eric M Knoche, Alison L Whitmer, Yan Yan, Bettina F Drake, Kristen M Sanfilippo

2020-Current year OA Pubs

BACKGROUND: Comorbid diseases influence patient outcomes, yet little is known about how comorbidities interact with treatments for metastatic castrate-resistant prostate cancer (mCRPC). No head-to-head trials have compared the efficacy of abiraterone and enzalutamide - oral androgen-receptor targeted agents (ARTAs) for mCRPC. In patients with comorbid disease, outcomes with ARTAs may differ due to disparate mechanisms of action, adverse events, and drug interactions.

METHODS: Retrospective observational study of US veterans initiating treatment for mCRPC with abiraterone or enzalutamide between September 2014 and June 2017. Treatment duration and overall survival (OS) was compared based on age and comorbid diseases. The association between …


Core Warming Of Coronavirus Disease 2019 Patients Undergoing Mechanical Ventilation: A Pilot Study, Nathaniel P Bonfanti, Nicholas M Mohr, David C Willms, Roger J Bedimo, Emily Gundert, Kristina L Goff, Erik B Kulstad, Anne M Drewry Dec 2023

Core Warming Of Coronavirus Disease 2019 Patients Undergoing Mechanical Ventilation: A Pilot Study, Nathaniel P Bonfanti, Nicholas M Mohr, David C Willms, Roger J Bedimo, Emily Gundert, Kristina L Goff, Erik B Kulstad, Anne M Drewry

2020-Current year OA Pubs

Fever is a recognized protective factor in patients with sepsis, and growing data suggest beneficial effects on outcomes in sepsis with elevated temperature, with a recent pilot randomized controlled trial (RCT) showing lower mortality by warming afebrile sepsis patients in the intensive care unit (ICU). The objective of this prospective single-site RCT was to determine if core warming improves respiratory physiology of mechanically ventilated patients with coronavirus disease 2019 (COVID-19), allowing earlier weaning from ventilation, and greater overall survival. A total of 19 patients with mean age of 60.5 (±12.5) years, 37% female, mean weight 95.1 (±18.6) kg, and mean …


Obesity And Outcomes Of Kawasaki Disease And Covid-19-Related Multisystem Inflammatory Syndrome In Children, Michael Khoury, William B Orr, Et Al. Dec 2023

Obesity And Outcomes Of Kawasaki Disease And Covid-19-Related Multisystem Inflammatory Syndrome In Children, Michael Khoury, William B Orr, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Obesity may affect the clinical course of Kawasaki disease (KD) in children and multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19.

OBJECTIVE: To compare the prevalence of obesity and associations with clinical outcomes in patients with KD or MIS-C.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, analysis of International Kawasaki Disease Registry (IKDR) data on contemporaneous patients was conducted between January 1, 2020, and July 31, 2022 (42 sites, 8 countries). Patients with MIS-C (defined by Centers for Disease Control and Prevention criteria) and patients with KD (defined by American Heart Association criteria) were included. Patients with …


Enlarged Perivascular Spaces In Infancy And Autism Diagnosis, Cerebrospinal Fluid Volume, And Later Sleep Problems, Dea Garic, Robert C Mckinstry, Kelly N Botteron, Et Al. Dec 2023

Enlarged Perivascular Spaces In Infancy And Autism Diagnosis, Cerebrospinal Fluid Volume, And Later Sleep Problems, Dea Garic, Robert C Mckinstry, Kelly N Botteron, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Perivascular spaces (PVS) and cerebrospinal fluid (CSF) are essential components of the glymphatic system, regulating brain homeostasis and clearing neural waste throughout the lifespan. Enlarged PVS have been implicated in neurological disorders and sleep problems in adults, and excessive CSF volume has been reported in infants who develop autism. Enlarged PVS have not been sufficiently studied longitudinally in infancy or in relation to autism outcomes or CSF volume.

OBJECTIVE: To examine whether enlarged PVS are more prevalent in infants who develop autism compared with controls and whether they are associated with trajectories of extra-axial CSF volume (EA-CSF) and sleep …


Local Treatment And Treatment-Related Adverse Effects Among Patients With Advanced Prostate Cancer, Saira Khan, Su-Hsin Chang, Mei Wang, Eric H Kim, Martin W Schoen, Carleena Rocuskie-Marker, Bettina F Drake Dec 2023

Local Treatment And Treatment-Related Adverse Effects Among Patients With Advanced Prostate Cancer, Saira Khan, Su-Hsin Chang, Mei Wang, Eric H Kim, Martin W Schoen, Carleena Rocuskie-Marker, Bettina F Drake

2020-Current year OA Pubs

IMPORTANCE: Recent data suggest that local treatment with radical prostatectomy or radiation may improve survival outcomes in men with advanced prostate cancer. However, evidence is lacking on treatment-related adverse effects among men with advanced prostate cancer.

OBJECTIVE: To assess the association of local treatment on treatment-related adverse effects among men diagnosed with advanced prostate cancer.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study assessed men diagnosed with advanced prostate cancer (defined as T4, N1, and/or M1 prostate cancer) between January 1, 1999, and December 31, 2013, with follow-up through December 31, 2021, who were treated at Veterans Health Administration medical centers. …


Greater Socioenvironmental Risk Factors And Higher Chronic Pain Stage Are Associated With Thinner Bilateral Temporal Lobes, Lisa H Antoine, Burel R Goodin, Et Al. Dec 2023

Greater Socioenvironmental Risk Factors And Higher Chronic Pain Stage Are Associated With Thinner Bilateral Temporal Lobes, Lisa H Antoine, Burel R Goodin, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Previous research indicates ethnic/race group differences in pain and neurodegenerative diseases. Accounting for socioenvironmental factors reduces ethnic/race group differences in clinical and experimental pain. In the current study sample, we previously reported that in individuals with knee pain, ethnic/race group differences were observed in bilateral temporal lobe thickness, areas of the brain associated with risk for Alzheimer's disease, and related dementias. The purpose of the study was to determine if socioenvironmental factors reduce or account for previously observed ethnic/race group differences and explore if a combined effect of socioenvironmental risk and chronic pain severity on temporal lobe cortices is …


Sex-Associated Differences In Frequencies And Prognostic Impact Of Recurrent Genetic Alterations In Adult Acute Myeloid Leukemia (Alliance, Amlcg), Michael Ozga, Geoffrey L Uy, Et Al. Nov 2023

Sex-Associated Differences In Frequencies And Prognostic Impact Of Recurrent Genetic Alterations In Adult Acute Myeloid Leukemia (Alliance, Amlcg), Michael Ozga, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

Clinical outcome of patients with acute myeloid leukemia (AML) is associated with demographic and genetic features. Although the associations of acquired genetic alterations with patients' sex have been recently analyzed, their impact on outcome of female and male patients has not yet been comprehensively assessed. We performed mutational profiling, cytogenetic and outcome analyses in 1726 adults with AML (749 female and 977 male) treated on frontline Alliance for Clinical Trials in Oncology protocols. A validation cohort comprised 465 women and 489 men treated on frontline protocols of the German AML Cooperative Group. Compared with men, women more often had normal …


Mycoplasma Genitalium In The Us (Mygenius): Surveillance Data From Sexual Health Clinics In 4 Us Regions, Lisa E Manhart, Gina Leipertz, Olusegun O Soge, Stephen J Jordan, Candice Mcneil, Preeti Pathela, Hilary Reno, Karen Wendel, Anika Parker, William M Geisler, Damon Getman, Matthew R Golden, Mygenius Study Team Nov 2023

Mycoplasma Genitalium In The Us (Mygenius): Surveillance Data From Sexual Health Clinics In 4 Us Regions, Lisa E Manhart, Gina Leipertz, Olusegun O Soge, Stephen J Jordan, Candice Mcneil, Preeti Pathela, Hilary Reno, Karen Wendel, Anika Parker, William M Geisler, Damon Getman, Matthew R Golden, Mygenius Study Team

2020-Current year OA Pubs

BACKGROUND: Mycoplasma genitalium (MG) is on the CDC Watch List of Antimicrobial Resistance Threats, yet there is no systematic surveillance to monitor change.

METHODS: We initiated surveillance in sexual health clinics in 6 cities, selecting a quota sample of urogenital specimens tested for gonorrhea and/or chlamydia. We abstracted patient data from medical records and detected MG and macrolide-resistance mutations (MRMs) by nucleic acid amplification testing. We used Poisson regression to estimate adjusted prevalence ratios (aPRs) and 95% CIs, adjusting for sampling criteria (site, birth sex, symptom status).

RESULTS: From October-December 2020 we tested 1743 urogenital specimens: 57.0% from males, 46.1% …