Anesthesiology Commons^™

Molecular Characterization Of Streptococcus Pneumoniae Causing Disease Among Children In Nigeria During The Introduction Of Pcv10 (Gsk), Stephanie W. Lo, Paulina A. Hawkins, Binta Jibir, Fatimah Hassan-Hanga, Mahmoud Gambo, Rasaq Olaosebikan, Grace Olanipekun, Huda Munir, Nicholas Kocmich, Amy J. Rezac-Elgohary, Safiya Gambo, Danstan Bagenda, Paul D. Fey, Robert F. Breiman, Lesley Mcgee, Stephen D. Bentley, Stephen K. Obaro, Community Acquired Pneumonia And Invasive Bacterial Disease Capibd Consortium

Journal Articles: Anesthesiology

Streptococcus pneumoniae (pneumococcus) is a leading vaccine-preventable cause of childhood invasive disease. Nigeria has the second highest pneumococcal disease burden globally, with an estimated ~49 000 child deaths caused by pneumococcal infections each year. Ten-valent pneumococcal conjugate vaccine (GSK; PCV10) was introduced in December 2014 in a phased approach. However, few studies have characterized the disease-causing pneumococci from Nigeria. This study assessed the prevalence of serotypes, antibiotic susceptibility and genomic lineages using whole genome sequencing and identified lineages that could potentially escape PCV10 (GSK). We also investigated the potential differences in pneumococcal lineage features between children with and …

Novel Rna-Seq Signatures Post-Methamphetamine And Oxycodone Use In A Model Of Hiv-Associated Neurocognitive Disorders, Pranavi Athota, Nghi M. Nguyen, Victoria L. Schaal, Sankarasubramanian Jagadesan, Chittibabu Guda, Sowmya V. Yelamanchili, Gurudutt Pendyala

Journal Articles: Anesthesiology

In the 21st century, the effects of HIV-associated neurocognitive disorders (HAND) have been significantly reduced in individuals due to the development of antiretroviral therapies (ARTs). However, the growing epidemic of polysubstance use (PSU) has led to concern for the effects of PSU on HIV-seropositive individuals. To effectively treat individuals affected by HAND, it is critical to understand the biological mechanisms affected by PSU, including the identification of novel markers. To fill this important knowledge gap, we used an in vivo HIV-1 Transgenic (HIV-1 Tg) animal model to investigate the effects of the combined use of chronic methamphetamine (METH) and oxycodone …

Identification Of Ywhah As A Novel Brain-Derived Extracellular Vesicle Marker Post Long-Term Midazolam Exposure During Early Development, Nghi M. Nguyen, Daniel Meyer, Luke Meyer, Subhash Chand, Jagadesan Sankarasubramanian, Maireen Miravite, Chittibabu Guda, Sowmya V. Yelamanchili, Gurudutt Pendyala

Journal Articles: Anesthesiology

Recently, the long-term use of sedative agents in the neonatal intensive care unit (NICU) has raised concerns about neurodevelopmental outcomes in exposed neonates. Midazolam (MDZ), a common neonatal sedative in the NICU, has been suggested to increase learning disturbances and cognitive impairment in children. However, molecular mechanisms contributing to such outcomes with long-term MDZ use during the early stages of life remain unclear. In this study, we for the first time elucidate the role of brain-derived extracellular vesicles (BDEVs), including mining the BDEV proteome post long-term MDZ exposure during early development. Employing our previously established rodent model system that mimics …

In Utero And Post-Natal Opioid Exposure Followed By Mild Traumatic Brain Injury Contributes To Cortical Neuroinflammation, Mitochondrial Dysfunction, And Behavioral Deficits In Juvenile Rats, Austin M. Gowen, Jina Yi, Kelly L. Stauch, Luke Miles, Sanjay Srinivasan, Katherine Odegaard, Gurudutt Pendyala, Sowmya V. Yelamanchili

Journal Articles: Anesthesiology

Maternal opioid use poses a significant health concern not just to the expectant mother but also to the fetus. Notably, increasing numbers of children born suffering from neonatal opioid withdrawal syndrome (NOWS) further compounds the crisis. While epidemiological research has shown the heightened risk factors associated with NOWS, little research has investigated what molecular mechanisms underly the vulnerabilities these children carry throughout development and into later life. To understand the implications of in utero and post-natal opioid exposure on the developing brain, we sought to assess the response to one of the most common pediatric injuries: minor traumatic brain injury …

Periocular Manifestation Of Obstructive Sleep Apnea As A Novel Perioperative Screening Tool, Megan Folsom, James Gigantelli, Brent Timperley, Kurtis Johnson, Danstan Bagenda, Huiling Pang, Sheila Ellis

Journal Articles: Anesthesiology

PURPOSE: Obstructive sleep apnea (OSA) presents perioperative challenges with increased risk for complications. Floppy eyelid syndrome (FES) is associated with OSA yet has not been addressed perioperatively. The current standard for perioperative OSA screening includes assessing patient risk factors or the STOP-BANG tool, which requires an active participant. We aimed to confirm a connection between FES and OSA in presurgical patients and develop a screening method appropriate for patients with perioperative OSA risk.

MATERIALS AND METHODS: 162 presurgical pre-anesthesia clinic patients were enrolled. Screening questions determined eligibility. Those who were pregnant or aged < 19 were excluded. Control group included those with a STOP-BANG score < 3. Experimental group included those with BMI > 35 and OSA diagnosis. Examiners photographed participants' …

Performance Of The Universal Vital Assessment (Uva) Mortality Risk Score In Hospitalized Adults With Infection In Rwanda: A Retrospective External Validation Study, Riley Hazard, Danstan Bagenda, Andrew J. Patterson, Julie T. Hoffman, Steven J. Lisco, Olivier Urayeneza, Polyphile Ntihinyurwa, Christopher C. Moore

Journal Articles: Anesthesiology

BACKGROUND: We previously derived a Universal Vital Assessment (UVA) score to better risk-stratify hospitalized patients in sub-Saharan Africa, including those with infection. Here, we aimed to externally validate the performance of the UVA score using previously collected data from patients hospitalized with acute infection in Rwanda.

METHODS: We performed a secondary analysis of data collected from adults ≥18 years with acute infection admitted to Gitwe District Hospital in Rwanda from 2016 until 2017. We calculated the UVA score from the time of admission and at 72 hours after admission. We also calculated quick sepsis-related organ failure assessment (qSOFA) and modified …

Methamphetamine Induces The Release Of Proadhesive Extracellular Vesicles And Promotes Syncytia Formation: A Potential Role In Hiv-1 Neuropathogenesis, Subhash Chand, Catherine Demarino, Austin Gowen, Maria Cowen, Sarah Al-Sharif, Fatah Kashanchi, Sowmya V. Yelamanchili

Journal Articles: Anesthesiology

Despite the success of combinational antiretroviral therapy (cART), the high pervasiveness of human immunodeficiency virus-1 (HIV)-associated neurocognitive disorders (HAND) poses a significant challenge for society. Methamphetamine (meth) and related amphetamine compounds, which are potent psychostimulants, are among the most commonly used illicit drugs. Intriguingly, HIV-infected individuals who are meth users have a comparatively higher rate of neuropsychological impairment and exhibit a higher viral load in the brain than infected individuals who do not abuse meth. Effectively, all cell types secrete nano-sized lipid membrane vesicles, referred to as extracellular vesicles (EVs) that can function as intercellular communication to modulate the physiology …

Effect Of Combined Methamphetamine And Oxycodone Use On The Synaptic Proteome In An In Vitro Model Of Polysubstance Use, Daniel Meyer, Pranavi Athota, Austin Gowen, Nghi M. Nguyen, Victoria L. Schaal, Sowmya V. Yelamanchili, Gurudutt Pendyala

Journal Articles: Anesthesiology

Polysubstance use (PSU) generally involves the simultaneous use of an opioid along with a stimulant. In recent years, this problem has escalated into a nationwide epidemic. Understanding the mechanisms and effects underlying the interaction between these drugs is essential for the development of treatments for those suffering from addiction. Currently, the effect of PSU on synapses-critical points of contact between neurons-remains poorly understood. Using an in vitro model of primary neurons, we examined the combined effects of the psychostimulant methamphetamine (METH) and the prescription opioid oxycodone (oxy) on the synaptic proteome using quantitative mass-spectrometry-based proteomics. A further ClueGO analysis and …

Extracellular Vesicles From Infected Cells Are Released Prior To Virion Release, Yuriy Kim, Gifty A. Mensah, Sarah Al Sharif, Daniel O. Pinto, Heather Branscome, Sowmya V. Yelamanchili, Maria Cowen, James Erickson, Pooja Khatkar, Renaud Mahieux, Fatah Kashanchi

Journal Articles: Anesthesiology

Here, we have attempted to address the timing of EV and virion release from virally infected cells. Uninfected (CEM), HIV-1-infected (J1.1), and human T cell leukemia virus-1 (HTLV-1)-infected (HUT102) cells were synchronized in G₀. Viral latency was reversed by increasing gene expression with the addition of serum-rich media and inducers. Supernatants and cell pellets were collected post-induction at different timepoints and assayed for extracellular vesicle (EV) and autophagy markers; and for viral proteins and RNAs. Tetraspanins and autophagy-related proteins were found to be differentially secreted in HIV-1- and HTLV-1-infected cells when compared with uninfected controls. HIV-1 proteins were …

Integrated Systems Analysis Of Mixed Neuroglial Cultures Proteome Post Oxycodone Exposure, Rahul Guda, Katherine E. Odegaard, Chengxi Tan, Victoria L. Schaal, Sowmya V. Yelamanchili, Gurudutt Pendyala

Journal Articles: Anesthesiology

Opioid abuse has become a major public health crisis that affects millions of individuals across the globe. This widespread abuse of prescription opioids and dramatic increase in the availability of illicit opioids have created what is known as the opioid epidemic. Pregnant women are a particularly vulnerable group since they are prescribed for opioids such as morphine, buprenorphine, and methadone, all of which have been shown to cross the placenta and potentially impact the developing fetus. Limited information exists regarding the effect of oxycodone (oxy) on synaptic alterations. To fill this knowledge gap, we employed an integrated system approach to …

Child Health And The Implementation Of Community And District-Management Empowerment For Scale-Up (Codes) In Uganda: A Randomised Controlled Trial, Peter Waiswa, Flavia Mpanga, Danstan Bagenda, Rornald Muhumuza Kananura, Thomas O'Connell, Dorcus Kiwanuka Henriksson, Theresa Diaz, Florence Ayebare, Anne Ruhweza Katahoire, Eric Ssegujja, Anthony Mbonye, Stefan Swartling Peterson

Journal Articles: Anesthesiology

INTRODUCTION: Uganda's district-level administrative units buttress the public healthcare system. In many districts, however, local capacity is incommensurate with that required to plan and implement quality health interventions. This study investigates how a district management strategy informed by local data and community dialogue influences health services.

METHODS: A 3-year randomised controlled trial (RCT) comprised of 16 Ugandan districts tested a management approach, Community and District-management Empowerment for Scale-up (CODES). Eight districts were randomly selected for each of the intervention and comparison areas. The approach relies on a customised set of data-driven diagnostic tools to identify and resolve health system bottlenecks. …

A Holistic Systems Approach To Characterize The Impact Of Pre- And Post-Natal Oxycodone Exposure On Neurodevelopment And Behavior, Katherine E. Odegaard, Victoria L. Schaal, Alexander R. Clark, Sneh Koul, Jagadesan Sankarasubramanian, Zhiqiu Xia, Melissa Mellon, Mariano Uberti, Yutong Liu, Andrew Stothert, Matthew J. Van Hook, Han-Jun Wang, Chittibabu Guda, Steven J. Lisco, Gurudutt Pendyala, Sowmya V. Yelamanchili

Journal Articles: Anesthesiology

Background: Increased risk of oxycodone (oxy) dependency during pregnancy has been associated with altered behaviors and cognitive deficits in exposed offspring. However, a significant knowledge gap remains regarding the effect of in utero and postnatal exposure on neurodevelopment and subsequent behavioral outcomes. Methods: Using a preclinical rodent model that mimics oxy exposure in utero (IUO) and postnatally (PNO), we employed an integrative holistic systems biology approach encompassing proton magnetic resonance spectroscopy (¹H-MRS), electrophysiology, RNA-sequencing, and Von Frey pain testing to elucidate molecular and behavioral changes in the exposed offspring during early neurodevelopment as well as adulthood. Results: ^{1 …}

A Comprehensive Study To Delineate The Role Of An Extracellular Vesicle-Associated Microrna-29a In Chronic Methamphetamine Use Disorder, Subhash Chand, Austin Gowen, Mason Savine, Dalia Moore, Alexander Clark, Wendy Huynh, Niming Wu, Katherine Odegaard, Lucas Weyrich, Rick A. Bevins, Howard S. Fox, Gurudutt Pendyala, Sowmya V. Yelamanchili

Journal Articles: Anesthesiology

Extracellular vesicles (EVs), which express a repertoire of cargo molecules (cf. proteins, microRNA, lipids, etc.), have been garnering a prominent role in the modulation of several cellular processes. Here, using both non-human primate and rodent model systems, we provide evidence that brain-derived EV (BDE) miRNA, miR-29a-3p (mir-29a), is significantly increased during chronic methamphetamine (MA) exposure. Further, miR-29a levels show significant increase both with drug-seeking and reinstatement in a rat MA self-administration model. We also show that EV-associated miR-29a is enriched in EV pool comprising of small EVs and exomeres and further plays a critical role in MA-induced inflammation and synaptodendritic …

Role Of Extracellular Vesicles In Substance Abuse And Hiv-Related Neurological Pathologies, Katherine E. Odegaard, Subhash Chand, Sydney Wheeler, Sneham Tiwari, Adrian Flores, Jordan Hernandez, Mason Savine, Austin Gowen, Gurudutt Pendyala, Sowmya V. Yelamanchili

Journal Articles: Anesthesiology

Extracellular vesicles (EVs) are a broad, heterogeneous class of membranous lipid-bilayer vesicles that facilitate intercellular communication throughout the body. As important carriers of various types of cargo, including proteins, lipids, DNA fragments, and a variety of small noncoding RNAs, including miRNAs, mRNAs, and siRNAs, EVs may play an important role in the development of addiction and other neurological pathologies, particularly those related to HIV. In this review, we summarize the findings of EV studies in the context of methamphetamine (METH), cocaine, nicotine, opioid, and alcohol use disorders, highlighting important EV cargoes that may contribute to addiction. Additionally, as HIV and …

Preventing Hiv And Hsv-2 Through Knowledge And Attitudes: A Replication Study Of A Multi-Component Community-Based Intervention In Zimbabwe, Fang Yu, Nicholas A. Hein, Danstan S. Bagenda

Journal Articles: Anesthesiology

INTRODUCTION: Approximately two-thirds of HIV-infected individuals reside in sub-Saharan Africa. The region accounts for 68% of the new HIV infections occurring worldwide with almost one-half of these infections being among young adults aged 12-24 years. Cowan and colleagues conducted a community-based, multi-component HIV intervention aimed at youth in rural Zimbabwe. Despite some changes in knowledge and attitudes, the community-based intervention did not affect the prevalence of HIV or HSV-2. We selected this frequently cited study for replication since it incorporates individual-, community-, and structural- level intervention components that are often considered in global HIV/AIDS prevention programs. Additionally, the intervention could …

The President's Emergency Plan For Aids Relief And Adult Mortality: A Replication Study Of Hiv Development Assistance Effects In Sub-Saharan African Countries, Nicholas A. Hein, Danstan Bagenda, Jiangtao Luo

Journal Articles: Anesthesiology

The US budget for global health funding, which was by far the largest of similar funding in the world, increased from US $1.3 billion in 2001 to more than US $10 billion in recent years. More than 54% of this funding was allocated to the Global Fund to Fight HIV/AIDS through the US President's Emergency Plan for AIDS Relief (PEPFAR) in Africa. However, recent studies indicate contradictory results regarding the effectiveness of PEPFAR. One by Bendavid, Holmes, Bhattacharya, and Miller shows positive effects of PEPFAR in reducing adult mortality in Africa, while another by Duber, Coates, Szekeras, Kaji, and Lewis …

Mesenchymal Stem Cell-Derived Extracellular Vesicles: Challenges In Clinical Applications, Austin Gowen, Farah Shahjin, Subhash Chand, Katherine E. Odegaard, Sowmya V. Yelamanchili

Journal Articles: Anesthesiology

Stem cell therapy has garnered much attention and application in the past decades for the treatment of diseases and injuries. Mesenchymal stem cells (MSCs) are studied most extensively for their therapeutic roles, which appear to be derived from their paracrine activity. Recent studies suggest a critical therapeutic role for extracellular vesicles (EV) secreted by MSCs. EV are nano-sized membrane-bound vesicles that shuttle important biomolecules between cells to maintain physiological homeostasis. Studies show that EV from MSCs (MSC-EV) have regenerative and anti-inflammatory properties. The use of MSC-EV, as an alternative to MSCs, confers several advantages, such as higher safety profile, lower …

Cash Transfers And Hiv/Hsv-2 Prevalence: A Replication Of A Cluster Randomized Trial In Malawi, Lynette M. Smith, Nicholas A. Hein, Danstan Bagenda

Journal Articles: Anesthesiology

INTRODUCTION: In this paper we perform a replication analysis of "Effect of a cash transfer programme for schooling on prevalence of HIV and herpes simplex type 2 in Malawi: a cluster randomised trial" by Sarah Baird and others published in "The Lancet" in 2012. The original study was a two-year cluster randomized intervention trial of never married girls aged 13-22 in Malawi. Enumeration areas were randomized to either an intervention involving cash transfer (conditional or unconditional of school enrollment) or control. The study included 1708 Malawian girls, who were enrolled at baseline and had biological testing for HIV and herpes …

Isolated Prehospital Hypotension Correlates With Injury Severity And Outcomes In Patients With Trauma, Clayton D. Damme, Jiangtao Luo, Keely L. Buesing

Journal Articles: Anesthesiology

Objective Patients normotensive in the trauma bay despite documented prehospital hypotension may not be recognized as significantly injured. The purpose of this study was to determine whether isolated prehospital hypotension portends poor outcomes and correlates with injury severity.

Methods Prospective cohort study conducted at a level 1 university trauma center. The lowest recorded prehospital systolic blood pressure (SBP) and the first recorded SBP on hospital arrival were used to divide patients into either the normotensive (NP) or hypotensive (HP) group. Patients who failed to achieve normotension on hospital arrival were excluded. Hypotension was defined as SBP≤110 mmHg.

Results Compared to …