Medicine and Health Sciences Commons^™

Myostatin Is A Negative Regulator Of Adult Neurogenesis After Spinal Cord Injury In Zebrafish, Vishnu Muraleedharan Saraswathy, Lili Zhou, Anthony R Mcadow, Brooke Burris, Deepika Dogra, Sven Reischauer, Mayssa H Mokalled

2020-Current year OA Pubs

Intrinsic and extrinsic inhibition of neuronal regeneration obstruct spinal cord (SC) repair in mammals. In contrast, adult zebrafish achieve functional recovery after complete SC transection. While studies of innate SC regeneration have focused on axon regrowth as a primary repair mechanism, how local adult neurogenesis affects functional recovery is unknown. Here, we uncover dynamic expression of zebrafish myostatin b (mstnb) in a niche of dorsal SC progenitors after injury. mstnb mutants show impaired functional recovery, normal glial and axonal bridging across the lesion, and an increase in the profiles of newborn neurons. Molecularly, neuron differentiation genes are upregulated, while the …

Chatbot-Delivered Cognitive Behavioral Therapy In Adolescents With Depression And Anxiety During The Covid-19 Pandemic: Feasibility And Acceptability Study, Ginger Nicol, Ruoyun Wang, Sharon Graham, Sherry Dodd, Jane Garbutt

2020-Current year OA Pubs

BACKGROUND: Symptoms of depression and anxiety, suicidal ideation, and self-harm have escalated among adolescents to crisis levels during the COVID-19 pandemic. As a result, primary care providers (PCPs) are often called on to provide first-line care for these youth. Digital health interventions can extend mental health specialty care, but few are evidence based. We evaluated the feasibility of delivering an evidence-based mobile health (mHealth) app with an embedded conversational agent to deliver cognitive behavioral therapy (CBT) to symptomatic adolescents presenting in primary care settings during the pandemic.

OBJECTIVE: In this 12-week pilot study, we evaluated the feasibility of delivering the …

Transversus Abdominis Plane Block With Different Bupivacaine Concentrations In Children Undergoing Unilateral Inguinal Hernia Repair: A Single-Blind Randomized Clinical Trial, Meltem Savran Karadeniz, Ayşe Gülşah Atasever, Emine Aysu Salviz, Emre Sertaç Bingül, Hayriye Şentürk Çiftçi, Müşerref Beril Dinçer, Mukadder Orhan Sungur

2020-Current year OA Pubs

BACKGROUND: Current knowledge on the ideal local anesthetic concentration for the ultrasound-guided transversus abdominis plane block (TAPB) in pediatrics is scarce. The purpose of this study is to compare the efficacy of US-guided TAPB at two different concentrations of bupivacaine in pediatrics undergoing unilateral inguinal hernia repair.

METHODS: After random allocation, 74 children aged 1-8 were randomized to receive US-guided TAPB by using 1 mg.kg

RESULTS: Sixty-four children were recruited for the study. Postoperative pain scores were equal between the two groups. There was no need for a rescue analgesic in any group after the postoperative 6

CONCLUSION: TAPB using …

Eeg-Based Grading Of Immune Effector Cell-Associated Neurotoxicity Syndrome, Daniel K Jones, Fábio A Nascimento, Et Al.

2020-Current year OA Pubs

CAR-T cell therapy is an effective cancer therapy for multiple refractory/relapsed hematologic malignancies but is associated with substantial toxicity, including Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). Improved detection and assessment of ICANS could improve management and allow greater utilization of CAR-T cell therapy, however, an objective, specific biomarker has not been identified. We hypothesized that the severity of ICANS can be quantified based on patterns of abnormal brain activity seen in electroencephalography (EEG) signals. We conducted a retrospective observational study of 120 CAR-T cell therapy patients who had received EEG monitoring. We determined a daily ICANS grade for each …

Structural Basis Of Synthetic Agonist Activation Of The Nuclear Receptor Rev-Erb, Meghan H Murray, Aurore Cecile Valfort, Thomas Koelblen, Céline Ronin, Fabrice Ciesielski, Arindam Chatterjee, Giri Babu Veerakanellore, Bahaa Elgendy, John K Walker, Lamees Hegazy, Thomas P Burris

2020-Current year OA Pubs

The nuclear receptor REV-ERB plays an important role in a range of physiological processes. REV-ERB behaves as a ligand-dependent transcriptional repressor and heme has been identified as a physiological agonist. Our current understanding of how ligands bind to and regulate transcriptional repression by REV-ERB is based on the structure of heme bound to REV-ERB. However, porphyrin (heme) analogues have been avoided as a source of synthetic agonists due to the wide range of heme binding proteins and potential pleotropic effects. How non-porphyrin synthetic agonists bind to and regulate REV-ERB has not yet been defined. Here, we characterize a high affinity …

Let's Talk About Antibiotics: A Randomised Trial Of Two Interventions To Reduce Antibiotic Misuse, Kathy Goggin, Emily A. Hurley, Brian R. Lee, Andrea Bradley-Ewing, Carey Bickford, Kimberly Pina, Evelyn Donis De Miranda, David Yu, Kirsten Weltmer, Sebastian Linnemayr, Christopher C. Butler, Jason G. Newland, Angela L Myers

2020-Current year OA Pubs

BACKGROUND: Children with acute respiratory tract infections (ARTIs) receive ≈11.4 million unnecessary antibiotic prescriptions annually. A noted contributor is inadequate parent-clinician communication, however, efforts to reduce overprescribing have only indirectly targeted communication or been impractical.

OBJECTIVES: Compare two feasible (higher vs lower intensity) interventions for enhancing parent-clinician communication on the rate of inappropriate antibiotic prescribing.

DESIGN: Multisite, parallel group, cluster randomised comparative effectiveness trial. Data collected between March 2017 and March 2019.

SETTING: Academic and private practice outpatient clinics.

PARTICIPANTS: Clinicians (n=41, 85% of eligible approached) and 1599 parent-child dyads (ages 1-5 years with ARTI symptoms, 71% of eligible approached). …

Return Of Non-Acmg Recommended Incidental Genetic Findings To Pediatric Patients: Considerations And Opportunities From Experiences In Genomic Sequencing, Kevin M Bowling, Michelle L Thompson, Melissa A Kelly, Sarah Scollon, Anne M Slavotinek, Bradford C Powell, Brian M Kirmse, Laura G Hendon, Kyle B Brothers, Bruce R Korf, Gregory M Cooper, John M Greally, Anna C E Hurst

2020-Current year OA Pubs

BACKGROUND: The uptake of exome/genome sequencing has introduced unexpected testing results (incidental findings) that have become a major challenge for both testing laboratories and providers. While the American College of Medical Genetics and Genomics has outlined guidelines for laboratory management of clinically actionable secondary findings, debate remains as to whether incidental findings should be returned to patients, especially those representing pediatric populations.

METHODS: The Sequencing Analysis and Diagnostic Yield working group in the Clinical Sequencing Evidence-Generating Research Consortium has collected a cohort of pediatric patients found to harbor a genomic sequencing-identified non-ACMG-recommended incidental finding. The incidental variants were not thought …

Multi-Method Investigation Of Factors Influencing Amyloid Onset And Impairment In Three Cohorts, Tobey J Betthauser, Dean F Wong, Et Al.

2020-Current year OA Pubs

Alzheimer's disease biomarkers are becoming increasingly important for characterizing the longitudinal course of disease, predicting the timing of clinical and cognitive symptoms, and for recruitment and treatment monitoring in clinical trials. In this work, we develop and evaluate three methods for modelling the longitudinal course of amyloid accumulation in three cohorts using amyloid PET imaging. We then use these novel approaches to investigate factors that influence the timing of amyloid onset and the timing from amyloid onset to impairment onset in the Alzheimer's disease continuum. Data were acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Baltimore Longitudinal Study of …

Effect Of Covid-19 On The Implementation Of A Multifaceted Intervention To Improve Teamwork And Quality For Hospitalized Patients: A Qualitative Interview Study, Iva A Terwilliger, Milisa Manojlovich, Julie K Johnson, Mark V Williams, Kevin J O'Leary

2020-Current year OA Pubs

BACKGROUND: Healthcare organizations made major adjustments to deliver care during the COVID pandemic, yet little is known about how these adjustments shaped ongoing quality and safety improvement efforts. We aimed to understand how COVID affected four U.S. hospitals' prospective implementation efforts in an ongoing quality improvement initiative, the REdesigning SystEms to Improve Teamwork and Quality for Hospitalized Patients (RESET) project, which implemented complementary interventions to redesign systems of care for medical patients.

METHODS: We conducted individual semi-structured interviews with 40 healthcare professionals to determine how COVID influenced RESET implementation. We used conventional qualitative content analysis to inductively code transcripts and …

De Novo Serine Biosynthesis From Glucose Predicts Sex-Specific Response To Antifolates In Non-Small Cell Lung Cancer Cell Lines, Jasmin Sponagel, Siddhartha Devarakonda, Joshua B Rubin, Jingqin Luo, Joseph E Ippolito

2020-Current year OA Pubs

Lung cancer is the leading cause of cancer-related death. Intriguingly, males with non-small cell lung cancer (NSCLC) have a higher mortality rate than females. Here, we investigated the role of serine metabolism as a predictive marker for sensitivity to the antifolate pemetrexed in male and female NSCLC cell lines. Using [

Evaluation Of Cisplatin-Induced Pathology In The Larval Zebrafish Lateral Line, David S Lee, Angela Schrader, Emily Bell, Mark E Warchol, Lavinia Sheets

2020-Current year OA Pubs

Cisplatin is an effective anticancer agent, but also causes permanent hearing loss by damaging hair cells-the sensory receptors essential for hearing. There is an urgent clinical need to protect cochlear hair cells in patients undergoing cisplatin chemotherapy. The zebrafish lateral line organ contains hair cells and has been frequently used in studies to screen for otoprotective compounds. However, these studies have employed a wide range of cisplatin dosages and exposure times. We therefore performed a comprehensive evaluation of cisplatin ototoxicity in the zebrafish lateral line with the goal of producing a standardized, clinically relevant protocol for future studies. To define …

An Mtorc1 To Hri Signaling Axis Promotes Cytotoxicity Of Proteasome Inhibitors In Multiple Myeloma, Odai Darawshi, Barbara Muz, Et Al.

2020-Current year OA Pubs

Multiple myeloma (MM) causes approximately 20% of deaths from blood cancers. Notwithstanding significant therapeutic progress, such as with proteasome inhibitors (PIs), MM remains incurable due to the development of resistance. mTORC1 is a key metabolic regulator, which frequently becomes dysregulated in cancer. While mTORC1 inhibitors reduce MM viability and synergize with other therapies in vitro, clinically, mTORC1 inhibitors are not effective for MM. Here we show that the inactivation of mTORC1 is an intrinsic response of MM to PI treatment. Genetically enforced hyperactivation of mTORC1 in MM was sufficient to compromise tumorigenicity in mice. In vitro, mTORC1-hyperactivated MM cells gained …

Open-Channel Structure Of A Pentameric Ligand-Gated Ion Channel Reveals A Mechanism Of Leaflet-Specific Phospholipid Modulation, John T Petroff 2nd, Noah M Dietzen, Ezry Santiago-Mcrae, Brett Deng, Maya S Washington, Lawrence J Chen, K Trent Moreland, Zengqin Deng, Michael Rau, James A J Fitzpatrick, Peng Yuan, Thomas T Joseph, Jérôme Hénin, Grace Brannigan, Wayland W L Cheng

2020-Current year OA Pubs

Pentameric ligand-gated ion channels (pLGICs) mediate synaptic transmission and are sensitive to their lipid environment. The mechanism of phospholipid modulation of any pLGIC is not well understood. We demonstrate that the model pLGIC, ELIC (Erwinia ligand-gated ion channel), is positively modulated by the anionic phospholipid, phosphatidylglycerol, from the outer leaflet of the membrane. To explore the mechanism of phosphatidylglycerol modulation, we determine a structure of ELIC in an open-channel conformation. The structure shows a bound phospholipid in an outer leaflet site, and structural changes in the phospholipid binding site unique to the open-channel. In combination with streamlined alchemical free energy …

Economic Evaluation Of Implementation Science Outcomes In Low- And Middle-Income Countries: A Scoping Review, Akash Malhotra, Abigail Barker, Victor G Davila-Roman, William Effah, Et Al.

2020-Current year OA Pubs

BACKGROUND: Historically, the focus of cost-effectiveness analyses has been on the costs to operate and deliver interventions after their initial design and launch. The costs related to design and implementation of interventions have often been omitted. Ignoring these costs leads to an underestimation of the true price of interventions and biases economic analyses toward favoring new interventions. This is especially true in low- and middle-income countries (LMICs), where implementation may require substantial up-front investment. This scoping review was conducted to explore the topics, depth, and availability of scientific literature on integrating implementation science into economic evaluations of health interventions in …

Collegiate Wrestler With A Bicuspid Aortic Valve And Aortic Dilation, Rahul Chhana, Christopher Rymer, Mahesh Vidula, Kristopher Fayock, Helene Glassberg, Chris Kusmiesz, Mustafa Husaini, Sanjay Sivalokanathan, Neel Chokshi, Sheela Krishnan

2020-Current year OA Pubs

Bicuspid aortic valve and aortopathy are generally considered contraindications to isometric exercise. For athletes with mild disease at low risk of adverse events, a shared decision-making approach for continued sports participation is reasonable. We present a case of a collegiate wrestler with bicuspid aortic valve and aortopathy to illustrate shared decision making. (

Slc7a8 Is A Key Amino Acids Supplier For The Metabolic Programs That Sustain Homeostasis And Activation Of Type 2 Innate Lymphoid Cells, Santosh K Panda, Do-Hyun Kim, Pritesh Desai, Patrick F Rodrigues, Raki Sudan, Susan Gilfillan, Marina Cella, Steven J Van Dyken, Marco Colonna

2020-Current year OA Pubs

Group 2 innate lymphoid cells (ILC2) are innate counterparts of T helper 2 (Th2) cells that maintain tissue homeostasis and respond to injuries through rapid interleukin (IL)-5 and IL-13 secretion. ILC2s depend on availability of arginine and branched-chain amino acids for sustaining cellular fitness, proliferation, and cytokine secretion in both steady state and upon activation. However, the contribution of amino acid transporters to ILC2 functions is not known. Here, we found that ILC2s selectively express

Relationship Of Neurite Architecture To Brain Activity During Task-Based Fmri, Christin Schifani, Colin Hawco, Arash Nazeri, Aristotle N Voineskos

2020-Current year OA Pubs

Functional MRI (fMRI) has been widely used to examine changes in neuronal activity during cognitive tasks. Commonly used measures of gray matter macrostructure (e.g., cortical thickness, surface area, volume) do not consistently appear to serve as structural correlates of brain function. In contrast, gray matter microstructure, measured using neurite orientation dispersion and density imaging (NODDI), enables the estimation of indices of neurite density (neurite density index; NDI) and organization (orientation dispersion index; ODI) in gray matter. Our study explored the relationship among neurite architecture, BOLD (blood-oxygen-level-dependent) fMRI, and cognition, using a large sample (n = 750) of young adults of …

Β-Amyloid Pet Harmonisation Across Longitudinal Studies: Application To Aibl, Adni And Oasis3, Pierrick Bourgeat, Manu Goyal, Pamela Lamontagne, John C Morris, Et Al.

2020-Current year OA Pubs

INTRODUCTION: The Centiloid scale was developed to harmonise the quantification of β-amyloid (Aβ) PET images across tracers, scanners, and processing pipelines. However, several groups have reported differences across tracers and scanners even after centiloid conversion. In this study, we aim to evaluate the impact of different pre and post-processing harmonisation steps on the robustness of longitudinal Centiloid data across three large international cohort studies.

METHODS: All Aβ PET data in AIBL (N = 3315), ADNI (N = 3442) and OASIS3 (N = 1398) were quantified using the MRI-based Centiloid standard SPM pipeline and the PET-only pipeline CapAIBL. SUVR were converted …

The Quality Of Energy- And Macronutrient-Balanced Diets Regulates Host Susceptibility To Influenza In Mice, Taylor A Cootes, Nayan D Bhattacharyya, Susie S Y Huang, Lina Daniel, Kim S Bell-Anderson, Sebastian A Stifter, Tracy Chew, Samantha M Solon-Biet, Luis R Saraiva, Yi Cai, Xinchun Chen, Stephen J Simpson, Carl G Feng

2020-Current year OA Pubs

Modulation of individual macronutrients or caloric density is known to regulate host resistance to infection in mice. However, the impact of diet composition, independent of macronutrient and energy content, on infection susceptibility is unclear. We show that two laboratory rodent diets, widely used as standard animal feeds and experimental controls, display distinct abilities in supporting mice during influenza infection. Mice placed on the highly processed AIN93G showed increased mortality to infection compared with those on a grain-based chow diet, suggesting a detrimental role for highly processed food in host defense. We further demonstrate that the heightened susceptibility of AIN93G-fed mice …

Race And Gender-Based Perceptions Of Older Septuagenarian Adults, Forest Melton, Kelly Palmer, Sade Solola, Luis Luy, Kathryn Herrera-Theut, Leanne Zabala, Shannon M Knapp, Ryan Yee, Erika Yee, Elizabeth Calhoun, Megan C Thomas Hebdon, Natalie Pool, Nancy Sweitzer, Khadijah Breathett

2020-Current year OA Pubs

OBJECTIVES: Older adults face racism, sexism, and ageism. As the U.S. population ages, it is important to understand how the current population views older adults.

METHODS: Participants recruited through Amazon's Mechanical Turk provided perceptions of older Black and White models' photographs. Using mixed-effect models, we assessed interactions between race and gender of participants and models.

RESULTS: Among Participants of Color and White participants (

DISCUSSION: Participants had few biases toward older Black and White models, while gender biases favored men.

Molecular Subclasses Of Clear Cell Ovarian Carcinoma And Their Impact On Disease Behavior And Outcomes, Kelly L Bolton, Irenaeus C C Chan, Brian J Wiley, Et Al.

2020-Current year OA Pubs

PURPOSE: To identify molecular subclasses of clear cell ovarian carcinoma (CCOC) and assess their impact on clinical presentation and outcomes.

EXPERIMENTAL DESIGN: We profiled 421 primary CCOCs that passed quality control using a targeted deep sequencing panel of 163 putative CCOC driver genes and whole transcriptome sequencing of 211 of these tumors. Molecularly defined subgroups were identified and tested for association with clinical characteristics and overall survival.

RESULTS: We detected a putative somatic driver mutation in at least one candidate gene in 95% (401/421) of CCOC tumors including ARID1A (in 49% of tumors), PIK3CA (49%), TERT (20%), and TP53 (16%). …

Inhibiting Ack1-Mediated Phosphorylation Of C-Terminal Src Kinase Counteracts Prostate Cancer Immune Checkpoint Blockade Resistance, Dhivya Sridaran, Surbhi Chouhan, Kiran Mahajan, Arun Renganathan, Cody Weimholt, Shambhavi Bhagwat, Melissa Reimers, Eric H Kim, Manish K Thakur, Muhammad A Saeed, Russell K Pachynski, Markus A Seeliger, W Todd Miller, Felix Y Feng, Nupam P Mahajan

2020-Current year OA Pubs

Solid tumours are highly refractory to immune checkpoint blockade (ICB) therapies due to the functional impairment of effector T cells and their inefficient trafficking to tumours. T-cell activation is negatively regulated by C-terminal Src kinase (CSK); however, the exact mechanism remains unknown. Here we show that the conserved oncogenic tyrosine kinase Activated CDC42 kinase 1 (ACK1) is able to phosphorylate CSK at Tyrosine 18 (pY18), which enhances CSK function, constraining T-cell activation. Mice deficient in the Tnk2 gene encoding Ack1, are characterized by diminished CSK Y18-phosphorylation and spontaneous activation of CD8

Structural Basis For Mechanotransduction In A Potassium-Dependent Mechanosensitive Ion Channel, Jonathan Mount, Grigory Maksaev, Brock T Summers, James A J Fitzpatrick, Peng Yuan

2020-Current year OA Pubs

Mechanosensitive channels of small conductance, found in many living organisms, open under elevated membrane tension and thus play crucial roles in biological response to mechanical stress. Amongst these channels, MscK is unique in that its activation also requires external potassium ions. To better understand this dual gating mechanism by force and ligand, we elucidate distinct structures of MscK along the gating cycle using cryo-electron microscopy. The heptameric channel comprises three layers: a cytoplasmic domain, a periplasmic gating ring, and a markedly curved transmembrane domain that flattens and expands upon channel opening, which is accompanied by dilation of the periplasmic ring. …

The Sod1-Mediated Als Phenotype Shows A Decoupling Between Age Of Symptom Onset And Disease Duration, Sarah Opie-Martin, Jennifer Jockel-Balsarotti, Taha Bali, Wade Self, Timothy Miller, Et Al.

2020-Current year OA Pubs

Superoxide dismutase (SOD1) gene variants may cause amyotrophic lateral sclerosis, some of which are associated with a distinct phenotype. Most studies assess limited variants or sample sizes. In this international, retrospective observational study, we compare phenotypic and demographic characteristics between people with SOD1-ALS and people with ALS and no recorded SOD1 variant. We investigate which variants are associated with age at symptom onset and time from onset to death or censoring using Cox proportional-hazards regression. The SOD1-ALS dataset reports age of onset for 1122 and disease duration for 883 people; the comparator population includes 10,214 and 9010 people respectively. Eight …

Enterotoxigenic Escherichia Coli Heat-Labile Toxin Drives Enteropathic Changes In Small Intestinal Epithelia, Alaullah Sheikh, Brunda Tumala, Tim J Vickers, John C Martin, Bruce A Rosa, Subrata Sabui, Supratim Basu, Rita D Simoes, Makedonka Mitreva, Chad Storer, Erik Tyksen, Richard D Head, Wandy Beatty, Hamid M Said, James M Fleckenstein

2020-Current year OA Pubs

Enterotoxigenic E. coli (ETEC) produce heat-labile (LT) and/or heat-stable (ST) enterotoxins, and commonly cause diarrhea in resource-poor regions. ETEC have been linked repeatedly to sequelae in children including enteropathy, malnutrition, and growth impairment. Although cellular actions of ETEC enterotoxins leading to diarrhea are well-established, their contributions to sequelae remain unclear. LT increases cellular cAMP to activate protein kinase A (PKA) that phosphorylates ion channels driving intestinal export of salt and water resulting in diarrhea. As PKA also modulates transcription of many genes, we interrogated transcriptional profiles of LT-treated intestinal epithelia. Here we show that LT significantly alters intestinal epithelial gene …

Collective Genomic Segments With Differential Pleiotropic Patterns Between Cognitive Dimensions And Psychopathology, Max Lam, Chia-Yen Chen, W David Hill, Charley Xia, Ruoyu Tian, Daniel F Levey, Joel Gelernter, Murray B Stein, Alexander S Hatoum, Hailiang Huang, Anil K Malhotra, Heiko Runz, Tian Ge, Todd Lencz

2020-Current year OA Pubs

Cognitive deficits are known to be related to most forms of psychopathology. Here, we perform local genetic correlation analysis as a means of identifying independent segments of the genome that show biologically interpretable pleiotropic associations between cognitive dimensions and psychopathology. We identify collective segments of the genome, which we call "meta-loci", showing differential pleiotropic patterns for psychopathology relative to either cognitive task performance (CTP) or performance on a non-cognitive factor (NCF) derived from educational attainment. We observe that neurodevelopmental gene sets expressed during the prenatal-early childhood period predominate in CTP-relevant meta-loci, while post-natal gene sets are more involved in NCF-relevant …

Sex Differences In Brain Tumor Glutamine Metabolism Reveal Sex-Specific Vulnerabilities To Treatment, Jasmin Sponagel, Jill K Jones, Cheryl Frankfater, Shanshan Zhang, Olivia Tung, Kevin Cho, Kelsey L Tinkum, Hannah Gass, Elena Nunez, Gary J Patti, Jingqin Luo, Joshua B Rubin, Joseph E Ippolito, Et Al.

2020-Current year OA Pubs

BACKGROUND: Brain cancer incidence and mortality rates are greater in males. Understanding the molecular mechanisms that underlie those sex differences could improve treatment strategies. Although sex differences in normal metabolism are well described, it is currently unknown whether they persist in cancerous tissue.

METHODS: Using positron emission tomography (PET) imaging and mass spectrometry, we assessed sex differences in glioma metabolism in samples from affected individuals. We assessed the role of glutamine metabolism in male and female murine transformed astrocytes using isotope labeling, metabolic rescue experiments, and pharmacological and genetic perturbations to modulate pathway activity.

FINDINGS: We found that male glioblastoma …

Imprinted Antibody Responses Against Sars-Cov-2 Omicron Sublineages, Young-Jun Park, Zhuoming Liu, Javier Janer, Sean P J Whelan, Herbert W Virgin, Et Al.

2020-Current year OA Pubs

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters elicit plasma-neutralizing antibodies against Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5, and that breakthrough infections, but not vaccination alone, induce neutralizing antibodies in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1, BA.2, and BA.4/5 receptor-binding domains, whereas Omicron primary infections elicit B cells of narrow specificity up to 6 months after …

Liquefied Petroleum Gas Or Biomass For Cooking And Effects On Birth Weight, Thomas F Clasen, Lindsay J Underhill, Et Al.

2020-Current year OA Pubs

BACKGROUND: Exposure during pregnancy to household air pollution caused by the burning of solid biomass fuel is associated with adverse health outcomes, including low birth weight. Whether the replacement of a biomass cookstove with a liquefied petroleum gas (LPG) cookstove would result in an increase in birth weight is unclear.

METHODS: We performed a randomized, controlled trial involving pregnant women (18 to <35 years of age and at 9 to <20 weeks' gestation as confirmed on ultrasonography) in Guatemala, India, Peru, and Rwanda. The women were assigned in a 1:1 ratio to use a free LPG cookstove and fuel (intervention group) or to continue using a biomass cookstove (control group). Birth weight, one of four prespecified primary outcomes, was the primary outcome for this report; data for the other three outcomes are not yet available. Birth weight was measured within 24 hours after birth. In addition, 24-hour personal exposures to fine particulate matter (particles with a diameter of ≤2.5 μm [PM

RESULTS: A total of 3200 women underwent randomization; 1593 were assigned to the intervention group, and 1607 to the control group. Uptake of the intervention was nearly complete, with traditional biomass cookstoves being used at a median rate …

Acute And Postacute Sequelae Associated With Sars-Cov-2 Reinfection, Benjamin Bowe, Yan Xie, Ziyad Al-Aly

2020-Current year OA Pubs

First infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risk of acute and postacute death and sequelae in various organ systems. Whether reinfection adds to risks incurred after first infection is unclear. Here we used the US Department of Veterans Affairs' national healthcare database to build a cohort of individuals with one SARS-CoV-2 infection (n = 443,588), reinfection (two or more infections, n = 40,947) and a noninfected control (n = 5,334,729). We used inverse probability-weighted survival models to estimate risks and 6-month burdens of death, hospitalization and incident sequelae. Compared to no reinfection, reinfection …