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Articles 5971 - 6000 of 10535

Full-Text Articles in Medicine and Health Sciences

A Randomized Controlled Trial In Schools Aimed At Exploring Mechanisms Of Change Of A Multifaceted Implementation Strategy For Promoting Mental Health At The Workplace, Lydia Kwak, Anna Toropova, Byron J Powell, Rebecca Lengnick-Hall, Irene Jensen, Gunnar Bergström, Liselotte Schäfer Elinder, Kjerstin Stigmar, Charlotte Wåhlin, Christina Björklund Sep 2022

A Randomized Controlled Trial In Schools Aimed At Exploring Mechanisms Of Change Of A Multifaceted Implementation Strategy For Promoting Mental Health At The Workplace, Lydia Kwak, Anna Toropova, Byron J Powell, Rebecca Lengnick-Hall, Irene Jensen, Gunnar Bergström, Liselotte Schäfer Elinder, Kjerstin Stigmar, Charlotte Wåhlin, Christina Björklund

2020-Current year OA Pubs

BACKGROUND: This study will explore implementation mechanisms through which a single implementation strategy and a multifaceted implementation strategy operate to affect the implementation outcome, which is fidelity to the Guideline For The Prevention of Mental Ill Health within schools. The guideline gives recommendations on how workplaces can prevent mental ill health among their personnel by managing social and organizational risks factors in the work environment. Schools are chosen as the setting for the study due to the high prevalence of mental ill health among teachers and other personnel working in schools. The study builds on our previous research, in which …


Trends In Matriculation From Neurological Surgery Training Programs Into Academic Versus Private Practice, Neha Siddiqui, Vamsi P. Reddy, James L. Rogers, Donald K. E. Detchou, Imaima Casubhoy, Rhea Gopali, Subhang Bhalla, Mika Janbahan, Emily Morris, Meghna Priyanka Peesapati, Nitin Agarwal Sep 2022

Trends In Matriculation From Neurological Surgery Training Programs Into Academic Versus Private Practice, Neha Siddiqui, Vamsi P. Reddy, James L. Rogers, Donald K. E. Detchou, Imaima Casubhoy, Rhea Gopali, Subhang Bhalla, Mika Janbahan, Emily Morris, Meghna Priyanka Peesapati, Nitin Agarwal

2020-Current year OA Pubs

OBJECTIVE: A career in academic neurosurgery is an arduous endeavor. Specific factors influencing physician practice preferences remain unclear. This study analyzes data from the American Association of Neurological Surgeons membership identifying the impact of several demographic and educational characteristics influencing neurosurgical career choices centered on academia, private practice, or a combination in the United States.

METHODS: A list of all current neurosurgeons was obtained from the American Association of Neurological Surgeons membership, and information on physician characteristics was collected via internet searches and institutional databases. The practice type of all neurosurgeons considered in this study were categorized as follows: private …


Lack Of Vmp1 Impairs Hepatic Lipoprotein Secretion And Promotes Non-Alcoholic Steatohepatitis, Xiaoxiao Jiang, Yan Xie, Nicholas O Davidson, Et Al. Sep 2022

Lack Of Vmp1 Impairs Hepatic Lipoprotein Secretion And Promotes Non-Alcoholic Steatohepatitis, Xiaoxiao Jiang, Yan Xie, Nicholas O Davidson, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: Vacuole membrane protein 1 (VMP1) is an endoplasmic reticulum (ER) transmembrane protein that regulates the formation of autophagosomes and lipid droplets. Recent evidence suggests that VMP1 plays a critical role in lipoprotein secretion in zebra fish and cultured cells. However, the pathophysiological roles and mechanisms by which VMP1 regulates lipoprotein secretion and lipid accumulation in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are unknown.

METHODS: Liver-specific and hepatocyte-specific Vmp1 knockout mice as well as Vmp1 knock-in mice were generated by crossing Vmp1

RESULTS: Hepatocyte-specific deletion of Vmp1 severely impaired VLDL secretion resulting in massive hepatic …


Mild Hypothermia Fails To Protect Infant Macaques From Brain Injury Caused By Prolonged Exposure To Antiseizure Drugs, Chrysanthy Ikonomidou, Sophie H Wang, Nicole A Fuhler, Shreya Larson, Saverio Capuano 3rd, Kevin R Brunner, Kristin Crosno, Heather A Simmons, Andres F Mejia, Kevin K Noguchi Sep 2022

Mild Hypothermia Fails To Protect Infant Macaques From Brain Injury Caused By Prolonged Exposure To Antiseizure Drugs, Chrysanthy Ikonomidou, Sophie H Wang, Nicole A Fuhler, Shreya Larson, Saverio Capuano 3rd, Kevin R Brunner, Kristin Crosno, Heather A Simmons, Andres F Mejia, Kevin K Noguchi

2020-Current year OA Pubs

Barbiturates and benzodiazepines are GABA


Rapidplan Hippocampal Sparing Whole Brain Model Version 2-How Far Can We Reduce The Dose?, Hefei Liu, Ryan Clark, Anthony Magliari, Robert Foster, Francisco Reynoso, Matthew Schmidt, Vinai Gondi, Christopher Abraham, Heather Curry, Patrick Kupelian, Deepak Khuntia, Sushil Beriwal Sep 2022

Rapidplan Hippocampal Sparing Whole Brain Model Version 2-How Far Can We Reduce The Dose?, Hefei Liu, Ryan Clark, Anthony Magliari, Robert Foster, Francisco Reynoso, Matthew Schmidt, Vinai Gondi, Christopher Abraham, Heather Curry, Patrick Kupelian, Deepak Khuntia, Sushil Beriwal

2020-Current year OA Pubs

Whole-brain radiotherapy has been the standard palliative treatment for patients with brain metastases due to its effectiveness, availability, and ease of administration. Recent clinical trials have shown that limiting radiation dose to the hippocampus is associated with decreased cognitive toxicity. In this study, we updated an existing Knowledge Based Planning model to further reduce dose to the hippocampus and improve other dosimetric plan quality characteristics. Forty-two clinical cases were contoured according to guidelines. A new dosimetric scorecard was created as an objective measure for plan quality. The new Hippocampal Sparing Whole Brain Version 2 (HSWBv2) model adopted a complex recursive …


The Nepenthesin Insert In The Plasmodium Falciparum Aspartic Protease Plasmepsin V Is Necessary For Enzyme Function, Alexander J Polino, Justin J Miller, Soumendranath Bhakat, Sumit Mukherjee, Suhas Bobba, Gregory R Bowman, Daniel E Goldberg Sep 2022

The Nepenthesin Insert In The Plasmodium Falciparum Aspartic Protease Plasmepsin V Is Necessary For Enzyme Function, Alexander J Polino, Justin J Miller, Soumendranath Bhakat, Sumit Mukherjee, Suhas Bobba, Gregory R Bowman, Daniel E Goldberg

2020-Current year OA Pubs

Plasmepsin V (PM V) is a pepsin-like aspartic protease essential for growth of the malarial parasite Plasmodium falciparum. Previous work has shown PM V to be an endoplasmic reticulum-resident protease that processes parasite proteins destined for export into the host cell. Depletion or inhibition of the enzyme is lethal during asexual replication within red blood cells as well as during the formation of sexual stage gametocytes. The structure of the Plasmodium vivax PM V has been characterized by X-ray crystallography, revealing a canonical pepsin fold punctuated by structural features uncommon to secretory aspartic proteases; however, the function of this unique …


A Mid-Level Health Manager Intervention To Promote Uptake Of Isoniazid Preventive Therapy Among People With Hiv In Uganda: A Cluster Randomised Trial, Elijah Kakande, Elvin H Geng, Et Al. Sep 2022

A Mid-Level Health Manager Intervention To Promote Uptake Of Isoniazid Preventive Therapy Among People With Hiv In Uganda: A Cluster Randomised Trial, Elijah Kakande, Elvin H Geng, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite longstanding guidelines endorsing isoniazid preventive therapy (IPT) for people with HIV, uptake is low across sub-Saharan Africa. Mid-level health managers oversee IPT programmes nationally; interventions aimed at this group have not been tested. We aimed to establish whether providing structured leadership and management training and facilitating subregional collaboration and routine data feedback to mid-level managers could increase IPT initiation among people with HIV compared with standard practice.

METHODS: We conducted a cluster randomised trial in Uganda among district-level health managers. We randomly assigned clusters of between four and seven managers in a 1:1 ratio to intervention or control …


The Transition To Parenthood In Obstetrics: Enhancing Prenatal Care For 2-Generation Impact, Catherine Monk, Sona Dimidjian, Ellen Galinsky, Kimberly D. Gregory, M. Camille Hoffman, Elizabeth A. Howell, Emily S. Miller, Cynthia Osborne, Cynthia E. Rogers, Darby E. Saxbe, Mary E. D'Alton Sep 2022

The Transition To Parenthood In Obstetrics: Enhancing Prenatal Care For 2-Generation Impact, Catherine Monk, Sona Dimidjian, Ellen Galinsky, Kimberly D. Gregory, M. Camille Hoffman, Elizabeth A. Howell, Emily S. Miller, Cynthia Osborne, Cynthia E. Rogers, Darby E. Saxbe, Mary E. D'Alton

2020-Current year OA Pubs

Obstetrics, the specialty overseeing infant and parent health before birth, could be expanded to address the interrelated areas of parents' prenatal impact on children's brain development and their own psychosocial needs during a time of immense change and neuroplasticity. Obstetrics is primed for the shift that is happening in pediatrics, which is moving from its traditional focus on physical health to a coordinated, whole-child, 2- or multigeneration approach. Pediatric care now includes developmental screening, parenting education, parent coaching, access to developmental specialists, brain-building caregiving skills, linkages to community resources, and tiered interventions with psychologists. Drawing on decades of developmental origins …


Clinical Trial Data Of Anti-Pd-1/Pd-L1 Therapy For Recurrent Or Metastatic Nasopharyngeal Carcinoma: A Review, Douglas R Adkins, Robert I. Haddad Sep 2022

Clinical Trial Data Of Anti-Pd-1/Pd-L1 Therapy For Recurrent Or Metastatic Nasopharyngeal Carcinoma: A Review, Douglas R Adkins, Robert I. Haddad

2020-Current year OA Pubs

IMPORTANCE: Anti-programmed cell death receptor-1 (PD-1) therapy is standard of care for incurable recurrent or metastatic non-nasopharyngeal head and neck cancer. In contrast, there are no regulatory agency-approved anti-PD-1 agents indicated for the treatment of recurrent or metastatic nasopharyngeal carcinomas (RM-NPC) in the Western hemisphere, and no standard treatment option exists beyond first-line chemotherapy for RM-NPC. The pace of development of novel systemic therapy regimens for RM-NPC has been slow compared to many other advanced tumor types, leaving an unmet clinical need for these patients with a poor prognosis.

OBSERVATIONS: Recent clinical trials have documented the clinical activity of anti-PD-1 …


Reference Ranges For Corpus Callosum And Cavum Septi Pellucidi Biometry On Prenatal Ultrasound: Systematic Review And Meta-Analysis, Joshua I Rosenbloom, Lauren H Yaeger, Shay Porat Sep 2022

Reference Ranges For Corpus Callosum And Cavum Septi Pellucidi Biometry On Prenatal Ultrasound: Systematic Review And Meta-Analysis, Joshua I Rosenbloom, Lauren H Yaeger, Shay Porat

2020-Current year OA Pubs

We conducted a systematic review and meta-analysis of published nomograms for fetal corpus callosum and cavum septi pellucid biometry. A structured literature search was conducted to identify studies that reported normal measurements of the fetal corpus callosum and cavum septi pellucidi. Random effects metaanalysis was used to calculate normal ranges, and reference curves are provided. The quality assessment demonstrated that there was generally poor reporting regarding maternal characteristics and neonatal outcomes. Our findings emphasize that standardization of research protocols and publishing criteria for normal biometric ranges is needed.


A Narrative Review Of Irritable Bowel Syndrome With Diarrhea: A Primer For Primary Care Providers, Baha Moshiree, Joel J Heidelbaugh, Gregory S Sayuk Sep 2022

A Narrative Review Of Irritable Bowel Syndrome With Diarrhea: A Primer For Primary Care Providers, Baha Moshiree, Joel J Heidelbaugh, Gregory S Sayuk

2020-Current year OA Pubs

Irritable bowel syndrome with diarrhea (IBS-D) is a chronic disorder of gut-brain interaction, characterized by recurrent abdominal pain in association with more frequent, loose stools. The pathophysiology of irritable bowel syndrome (IBS) includes disordered gut motility, alterations in gut microbiota, neural-hormonal system abnormalities, immune reactivity, and visceral hypersensitivity. Timely diagnosis of IBS-D can be achieved easily using clinical criteria. Formal IBS diagnosis is important for optimizing treatment and patient outcomes and facilitating patient access to appropriate educational resources. Yet, given the symptom overlap with other gastrointestinal conditions, diagnosis of IBS-D often is perceived to be challenging. Treatment of IBS includes …


Pharmacophore Modeling For Biological Targets With High Flexibility: Lxrβ Case Study, Sophia Kchouk, Lamees Hegazy Sep 2022

Pharmacophore Modeling For Biological Targets With High Flexibility: Lxrβ Case Study, Sophia Kchouk, Lamees Hegazy

2020-Current year OA Pubs

No abstract provided.


Evolution Of Multiple Domains Of The Hiv-1 Envelope Glycoprotein During Coreceptor Switch With Ccr5 Antagonist Therapy, Yueqi Du, Ellen Wu, Xiang Gao, Jie Zhang, John C Martin, Bruce A Rosa, Makedonka Mitreva, Lee Ratner Aug 2022

Evolution Of Multiple Domains Of The Hiv-1 Envelope Glycoprotein During Coreceptor Switch With Ccr5 Antagonist Therapy, Yueqi Du, Ellen Wu, Xiang Gao, Jie Zhang, John C Martin, Bruce A Rosa, Makedonka Mitreva, Lee Ratner

2020-Current year OA Pubs

HIV-1 uses CD4 as a receptor and chemokine receptors CCR5 and/or CXCR4 as coreceptors. CCR5 antagonists are a class of antiretrovirals used to inhibit viral entry. Phenotypic prediction algorithms such as Geno2Pheno are used to assess CCR5 antagonist eligibility, for which the V3 region is screened. However, there exist scenarios where the algorithm cannot give an accurate prediction of tropism. The current study examined coreceptor shift of HIV-1 from CCR5-tropic strains to CXCR4-tropic or dual-tropic strains among five subjects in a clinical trial of the CCR5 antagonist vicriviroc. Envelope gene amplicon libraries were constructed and subjected to next-generation sequencing, as …


Membrane Integrity Contributes To Resistance Of Cryptococcus Neoformans To The Cell Wall Inhibitor Caspofungin, Brenda Moreira-Walsh, Abigail Ragsdale, Woei Lam, Rajendra Upadhya, Evan Xu, Jennifer K Lodge, Maureen J Donlin Aug 2022

Membrane Integrity Contributes To Resistance Of Cryptococcus Neoformans To The Cell Wall Inhibitor Caspofungin, Brenda Moreira-Walsh, Abigail Ragsdale, Woei Lam, Rajendra Upadhya, Evan Xu, Jennifer K Lodge, Maureen J Donlin

2020-Current year OA Pubs

The fungal pathogen Cryptococcus neoformans causes up to 278 000 infections each year globally, resulting in up to 180,000 deaths annually, mostly impacting immunocompromised people. Therapeutic options for C. neoformans infections are very limited. Caspofungin, a member of the echinocandin class of antifungals, is generally well tolerated but clinically ineffective against C. neoformans. We sought to identify biological processes that can be targeted to render the cell more susceptible to echinocandins by screening the available libraries of gene deletion mutants made in the KN99α background for caspofungin sensitivity. We adapted a Candida albicans fungal biofilm assay for the growth characteristics …


Proteomic Identification Of Potential Target Proteins Of Cathepsin W For Its Development As A Drug Target For Influenza, Sira C Günther, Carles Martínez-Romero, Milagros Sempere Borau, Christine T N Pham, Adolfo García-Sastre, Silke Stertz Aug 2022

Proteomic Identification Of Potential Target Proteins Of Cathepsin W For Its Development As A Drug Target For Influenza, Sira C Günther, Carles Martínez-Romero, Milagros Sempere Borau, Christine T N Pham, Adolfo García-Sastre, Silke Stertz

2020-Current year OA Pubs

Influenza A virus (IAV) coopts numerous host factors for efficient replication. The cysteine protease cathepsin W (CTSW) has been identified as one host factor required for IAV entry, specifically for the escape of IAVs from late endosomes. However, the substrate specificity of CTSW and the proviral mechanism are thus far unknown. Here, we show that intracellular but not secreted CTSW promotes viral entry. We reveal 79 potential direct and 31 potential indirect cellular target proteins of CTSW using the high-throughput proteomic approach terminal amine isotopic labeling of substrates (TAILS) and determine the cleavage motif shared by the substrates of CTSW. …


Optimal Urine Culture Diagnostic Stewardship Practice- Results From An Expert Modified-Delphi Procedure, Kimberly C Claeys, Stephen Y Liang, Et Al. Aug 2022

Optimal Urine Culture Diagnostic Stewardship Practice- Results From An Expert Modified-Delphi Procedure, Kimberly C Claeys, Stephen Y Liang, Et Al.

2020-Current year OA Pubs

BACKGROUND: Urine cultures are nonspecific and often lead to misdiagnosis of urinary tract infection and unnecessary antibiotics. Diagnostic stewardship is a set of procedures that modifies test ordering, processing, and reporting in order to optimize diagnosis and downstream treatment. In this study, we aimed to develop expert guidance on best practices for urine culture diagnostic stewardship.

METHODS: A RAND-modified Delphi approach with a multidisciplinary expert panel was used to ascertain diagnostic stewardship best practices. Clinical questions to guide recommendations were grouped into three thematic areas (ordering, processing, reporting) in practice settings of emergency department, inpatient, ambulatory, and long-term care. Fifteen …


N1-Methylpseudouridine Found Within Covid-19 Mrna Vaccines Produces Faithful Protein Products, Kyusik Q Kim, Bhagyashri D Burgute, Shin-Cheng Tzeng, Crystal Jing, Courtney Jungers, Junya Zhang, Liewei L Yan, Richard D Vierstra, Sergej Djuranovic, Bradley S Evans, Hani S Zaher Aug 2022

N1-Methylpseudouridine Found Within Covid-19 Mrna Vaccines Produces Faithful Protein Products, Kyusik Q Kim, Bhagyashri D Burgute, Shin-Cheng Tzeng, Crystal Jing, Courtney Jungers, Junya Zhang, Liewei L Yan, Richard D Vierstra, Sergej Djuranovic, Bradley S Evans, Hani S Zaher

2020-Current year OA Pubs

Synthetic mRNA technology is a promising avenue for treating and preventing disease. Key to the technology is the incorporation of modified nucleotides such as N1-methylpseudouridine (m1Ψ) to decrease immunogenicity of the RNA. However, relatively few studies have addressed the effects of modified nucleotides on the decoding process. Here, we investigate the effect of m1Ψ and the related modification pseudouridine (Ψ) on translation. In a reconstituted system, we find that m1Ψ does not significantly alter decoding accuracy. More importantly, we do not detect an increase in miscoded peptides when mRNA containing m1Ψ is translated in cell culture, compared with unmodified mRNA. …


Re-Examining Rotavirus Innate Immune Evasion: Potential Applications Of The Reverse Genetics System, Avan Antia, Amanda N Pinski, Siyuan Ding Aug 2022

Re-Examining Rotavirus Innate Immune Evasion: Potential Applications Of The Reverse Genetics System, Avan Antia, Amanda N Pinski, Siyuan Ding

2020-Current year OA Pubs

Rotaviruses represent one of the most successful pathogens in the world, with high infectivity and efficient transmission between the young of many animal species, including humans. To overcome host defenses, rotaviruses have evolved a plethora of strategies to effectively evade the innate immune response, establish initial infection in the small intestine, produce progeny, and shed into the environment. Previously, studying the roles and relative contributions of specific rotaviral factors in innate immune evasion had been challenging without a plasmid-only reverse genetics system. Although still in its infancy, current reverse genetics technology will help address important research questions regarding rotavirus innate …


Blocking Chop-Dependent Txnip Shuttling To Mitochondria Attenuates Albuminuria And Mitigates Kidney Injury In Nephrotic Syndrome, Sun-Ji Park, Yeawon Kim, Chuang Li, Junwoo Suh, Jothilingam Sivapackiam, Tassia M Goncalves, George Jarad, Guoyan Zhao, Fumihiko Urano, Vijay Sharma, Ying Maggie Chen Aug 2022

Blocking Chop-Dependent Txnip Shuttling To Mitochondria Attenuates Albuminuria And Mitigates Kidney Injury In Nephrotic Syndrome, Sun-Ji Park, Yeawon Kim, Chuang Li, Junwoo Suh, Jothilingam Sivapackiam, Tassia M Goncalves, George Jarad, Guoyan Zhao, Fumihiko Urano, Vijay Sharma, Ying Maggie Chen

2020-Current year OA Pubs

Albuminuria is a hallmark of glomerular disease of various etiologies. It is not only a symptom of glomerular disease but also a cause leading to glomerulosclerosis, interstitial fibrosis, and eventually, a decline in kidney function. The molecular mechanism underlying albuminuria-induced kidney injury remains poorly defined. In our genetic model of nephrotic syndrome (NS), we have identified CHOP (C/EBP homologous protein)-TXNIP (thioredoxin-interacting protein) as critical molecular linkers between albuminuria-induced ER dysfunction and mitochondria dyshomeostasis. TXNIP is a ubiquitously expressed redox protein that binds to and inhibits antioxidant enzyme, cytosolic thioredoxin 1 (Trx1), and mitochondrial Trx2. However, very little is known about …


A Pilot Randomized Trial To Examine Effects Of A Hybrid Closed-Loop Insulin Delivery System On Neurodevelopmental And Cognitive Outcomes In Adolescents With Type 1 Diabetes, Allan L Reiss, Ana Maria Arbelaez, Et Al Aug 2022

A Pilot Randomized Trial To Examine Effects Of A Hybrid Closed-Loop Insulin Delivery System On Neurodevelopmental And Cognitive Outcomes In Adolescents With Type 1 Diabetes, Allan L Reiss, Ana Maria Arbelaez, Et Al

2020-Current year OA Pubs

Type 1 diabetes (T1D) is associated with lower scores on tests of cognitive and neuropsychological function and alterations in brain structure and function in children. This proof-of-concept pilot study (ClinicalTrials.gov Identifier NCT03428932) examined whether MRI-derived indices of brain development and function and standardized IQ scores in adolescents with T1D could be improved with better diabetes control using a hybrid closed-loop insulin delivery system. Eligibility criteria for participation in the study included age between 14 and 17 years and a diagnosis of T1D before 8 years of age. Randomization to either a hybrid closed-loop or standard diabetes care group was performed …


A Multitrait Locus Regulates Sarbecovirus Pathogenesis, Alexandra Schäfer, Emma S Winkler, Michael S Diamond, Et Al Aug 2022

A Multitrait Locus Regulates Sarbecovirus Pathogenesis, Alexandra Schäfer, Emma S Winkler, Michael S Diamond, Et Al

2020-Current year OA Pubs

Infectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genome-wide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to severe acute respiratory syndrome coronavirus (SARS-CoV) disease outcomes. We find several loci control differential …


Spatiotemporal Correlation Analysis Of Hydraulic Fracturing And Stroke In The United States, Chuanbo Hu, Bin Liu, Shuo Wang, Zhenduo Zhu, Amelia Adcock, James Simpkins, Xin Li Aug 2022

Spatiotemporal Correlation Analysis Of Hydraulic Fracturing And Stroke In The United States, Chuanbo Hu, Bin Liu, Shuo Wang, Zhenduo Zhu, Amelia Adcock, James Simpkins, Xin Li

2020-Current year OA Pubs

Hydraulic fracturing or fracking has led to a rapid growth of oil and gas production in the United States, but the impact of fracking on public health is an important but underresearched topic. We designed a methodology to study spatiotemporal correlations between the risk of fracking and stroke mortality. An annualized loss expectancy (ALE) model is applied to quantify the risk of fracking. The geographically and temporally weighted regression (GTWR) model is used to analyze spatiotemporal correlations of stroke mortality, fracking ALE, and nine other socioeconomic- and health-related factors. The analysis shows that fracking ALE is moderately correlated with stroke …


Comparative Risks Of Initial Aortic Events Associated With Genetic Thoracic Aortic Disease, Ellen S. Regalado, Alan C. Braverman, Et Al. Aug 2022

Comparative Risks Of Initial Aortic Events Associated With Genetic Thoracic Aortic Disease, Ellen S. Regalado, Alan C. Braverman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Pathogenic variants in 11 genes predispose individuals to heritable thoracic aortic disease (HTAD), but limited data are available to stratify the risk for aortic events associated with these genes.

OBJECTIVES: This study sought to compare the risk of first aortic event, specifically thoracic aortic aneurysm surgery or an aortic dissection, among 7 HTAD genes and variant types within each gene.

METHODS: A retrospective cohort of probands and relatives with rare variants in 7 genes for HTAD (n = 1,028) was assessed for the risk of first aortic events based on the gene altered, pathogenic variant type, sex, proband status, …


Distinct Sensitivities To Sars-Cov-2 Variants In Vaccinated Humans And Mice, Alexandra C Walls, Laura A Vanblargan, Michael S Diamond, Et Al. Aug 2022

Distinct Sensitivities To Sars-Cov-2 Variants In Vaccinated Humans And Mice, Alexandra C Walls, Laura A Vanblargan, Michael S Diamond, Et Al.

2020-Current year OA Pubs

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has led to the development of a large number of vaccines, several of which are now approved for use in humans. Understanding vaccine-elicited antibody responses against emerging SARS-CoV-2 variants of concern (VOCs) in real time is key to inform public health policies. Serum neutralizing antibody titers are the current best correlate of protection from SARS-CoV-2 challenge in non-human primates and a key metric to understand immune evasion of VOCs. We report that vaccinated BALB/c mice do not recapitulate faithfully the breadth and potency of neutralizing antibody responses elicited …


Subcortical-Cortical Dynamical States Of The Human Brain And Their Breakdown In Stroke, Chiara Favaretto, Michele Allegra, Gustavo Deco, Nicholas V Metcalf, Joseph C Griffis, Gordon L Shulman, Andrea Brovelli, Maurizio Corbetta Aug 2022

Subcortical-Cortical Dynamical States Of The Human Brain And Their Breakdown In Stroke, Chiara Favaretto, Michele Allegra, Gustavo Deco, Nicholas V Metcalf, Joseph C Griffis, Gordon L Shulman, Andrea Brovelli, Maurizio Corbetta

2020-Current year OA Pubs

The mechanisms controlling dynamical patterns in spontaneous brain activity are poorly understood. Here, we provide evidence that cortical dynamics in the ultra-slow frequency range (<0.01-0.1 Hz) requires intact cortical-subcortical communication. Using functional magnetic resonance imaging (fMRI) at rest, we identify Dynamic Functional States (DFSs), transient but recurrent clusters of cortical and subcortical regions synchronizing at ultra-slow frequencies. We observe that shifts in cortical clusters are temporally coincident with shifts in subcortical clusters, with cortical regions flexibly synchronizing with either limbic regions (hippocampus/amygdala), or subcortical nuclei (thalamus/basal ganglia). Focal lesions induced by stroke, especially those damaging white matter connections between basal ganglia/thalamus and cortex, provoke anomalies in the fraction times, dwell times, and transitions between DFSs, causing a bias toward abnormal network integration. Dynamical anomalies observed 2 weeks after stroke recover in time and contribute to explaining neurological impairment and long-term outcome.


Capg Is Required For Ebola Virus Infection By Controlling Virus Egress From Infected Cells, Hiroyuki Mori, James P Connell, Callie J Donahue, Ruthmabel Boytz, Yen Thi Kim Nguyen, Daisy W Leung, Douglas J Lacount, Robert A Davey Aug 2022

Capg Is Required For Ebola Virus Infection By Controlling Virus Egress From Infected Cells, Hiroyuki Mori, James P Connell, Callie J Donahue, Ruthmabel Boytz, Yen Thi Kim Nguyen, Daisy W Leung, Douglas J Lacount, Robert A Davey

2020-Current year OA Pubs

The replication of Ebola virus (EBOV) is dependent upon actin functionality, especially at cell entry through macropinocytosis and at release of virus from cells. Previously, major actin-regulatory factors involved in actin nucleation, such as Rac1 and Arp2/3, were shown important in both steps. However, downstream of nucleation, many other cell factors are needed to control actin dynamics. How these regulate EBOV infection remains largely unclear. Here, we identified the actin-regulating protein, CAPG, as important for EBOV replication. Notably, knockdown of CAPG specifically inhibited viral infectivity and yield of infectious particles. Cell-based mechanistic analysis revealed a requirement of CAPG for virus …


Apoptosis Detection In Retinal Ganglion Cells Using Quantitative Changes In Multichannel Fluorescence Colocalization, Xudong Qiu, Seth T Gammon, James R Johnson, Federica Pisaneschi, Steven W Millward, Edward M Barnett, David Piwnica-Worms Aug 2022

Apoptosis Detection In Retinal Ganglion Cells Using Quantitative Changes In Multichannel Fluorescence Colocalization, Xudong Qiu, Seth T Gammon, James R Johnson, Federica Pisaneschi, Steven W Millward, Edward M Barnett, David Piwnica-Worms

2020-Current year OA Pubs

KcapTR488 is a dual-fluorophore peptide sensor for the real-time reporting of programmed cell death by fluorescence imaging. KcapTR488 contains a nuclear localization sequence (NLS) conjugated with Texas Red, a caspase-cleavable sequence (DEVD), and a C-terminus conjugated to Alexa Fluor 488 (AF488). The synthesis and preliminary evaluation in cellulo of KcapTR488 for monitoring cell death by fluorescence imaging has been previously reported, but its utility in vivo has yet to be tested or validated. Herein, in vitro solution experiments verified the intramolecular fluorescence resonance energy transfer (FRET) between the two fluorophores and enabled a quantitative analysis of enzyme rates and selectivity. …


Organization Of The Gravity-Sensing System In Zebrafish, Zhikai Liu, David G C Hildebrand, Joshua L Morgan, Yizhen Jia, Nicholas Slimmon, Martha W Bagnall Aug 2022

Organization Of The Gravity-Sensing System In Zebrafish, Zhikai Liu, David G C Hildebrand, Joshua L Morgan, Yizhen Jia, Nicholas Slimmon, Martha W Bagnall

2020-Current year OA Pubs

Motor circuits develop in sequence from those governing fast movements to those governing slow. Here we examine whether upstream sensory circuits are organized by similar principles. Using serial-section electron microscopy in larval zebrafish, we generated a complete map of the gravity-sensing (utricular) system spanning from the inner ear to the brainstem. We find that both sensory tuning and developmental sequence are organizing principles of vestibular topography. Patterned rostrocaudal innervation from hair cells to afferents creates an anatomically inferred directional tuning map in the utricular ganglion, forming segregated pathways for rostral and caudal tilt. Furthermore, the mediolateral axis of the ganglion …


Statistical Validation Of Risk Alleles In Genetic Addiction Risk Severity (Gars) Test: Early Identification Of Risk For Alcohol Use Disorder (Aud) In 74,566 Case-Control Subjects, Kenneth Blum, Mark S Gold, Et Al. Aug 2022

Statistical Validation Of Risk Alleles In Genetic Addiction Risk Severity (Gars) Test: Early Identification Of Risk For Alcohol Use Disorder (Aud) In 74,566 Case-Control Subjects, Kenneth Blum, Mark S Gold, Et Al.

2020-Current year OA Pubs

Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in


Neurogenetic And Epigenetic Aspects Of Cannabinoids, Catherine A Dennen, Kenneth Blum, Abdalla Bowirrat, Jag Khalsa, Panayotis K Thanos, David Baron, Rajendra D Badgaiyan, Ashim Gupta, Eric R Braverman, Mark S Gold Aug 2022

Neurogenetic And Epigenetic Aspects Of Cannabinoids, Catherine A Dennen, Kenneth Blum, Abdalla Bowirrat, Jag Khalsa, Panayotis K Thanos, David Baron, Rajendra D Badgaiyan, Ashim Gupta, Eric R Braverman, Mark S Gold

2020-Current year OA Pubs

Cannabis is one of the most commonly used and abused illicit drugs in the world today. The United States (US) currently has the highest annual prevalence rate of cannabis consumption in the world, 17.9% in individuals aged 12 or older, and it is on the rise. With increasing cannabis use comes the potential for an increase in abuse, and according to the Substance Abuse and Mental Health Services Administration (SAMHSA), approximately 5.1% of Americans had Cannabis Use Disorder (CUD) in 2020. Research has shown that genetics and epigenetics play a significant role in cannabis use and CUD. In fact, approximately …