Publications by authors named "L Monique Ward"

1,812 Publications

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Acute Effects of Cheddar Cheese Consumption on Circulating Amino Acids and Human Skeletal Muscle.

Nutrients 2021 Feb 13;13(2). Epub 2021 Feb 13.

Department of Nutrition and Integrative Physiology, University of Utah, 250 S 1850 E, Salt Lake City, UT 84112, USA.

Cheddar cheese is a protein-dense whole food and high in leucine content. However, no information is known about the acute blood amino acid kinetics and protein anabolic effects in skeletal muscle in healthy adults. Therefore, we conducted a crossover study in which men and women ( = 24; ~27 years, ~23 kg/m) consumed cheese (20 g protein) or an isonitrogenous amount of milk. Blood and skeletal muscle biopsies were taken before and during the post absorptive period following ingestion. We evaluated circulating essential and non-essential amino acids, insulin, and free fatty acids and examined skeletal muscle anabolism by mTORC1 cellular localization, intracellular signaling, and ribosomal profiling. We found that cheese ingestion had a slower yet more sustained branched-chain amino acid circulation appearance over the postprandial period peaking at ~120 min. Cheese also modestly stimulated mTORC1 signaling and increased membrane localization. Using ribosomal profiling we found that, though both milk and cheese stimulated a muscle anabolic program associated with mTORC1 signaling that was more evident with milk, mTORC1 signaling persisted with cheese while also inducing a lower insulinogenic response. We conclude that Cheddar cheese induced a sustained blood amino acid and moderate muscle mTORC1 response yet had a lower glycemic profile compared to milk.
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http://dx.doi.org/10.3390/nu13020614DOI Listing
February 2021

Epidemiology, Clinical Features, and Outcomes of Hospitalized Adults with COVID-19: Early Experience from an Academic Medical Center in Mississippi.

South Med J 2021 03;114(3):144-149

From the Department of Medicine, Divisions of Infectious Diseases, Pulmonary, and Critical Care, and Hospital Medicine, and the Department of Population Health Science, John D. Bower School of Population Health, University of Mississippi Medical Center, Jackson.

Objectives: To describe the demographics, clinical characteristics, and outcomes of hospitalized adults with coronavirus disease 2019 (COVID-19) in an academic medical center in the southern United States.

Methods: Retrospective, observational cohort study of all adult patients (18 years and older) consecutively admitted with laboratory-confirmed severe acute respiratory syndrome-coronavirus-2 infection between March 13 and April 25, 2020 at the University of Mississippi Medical Center. All of the patients either survived to hospital discharge or died during hospitalization. Demographics, body mass index, comorbidities, clinical manifestations, and laboratory findings were collected. Patient outcomes (need for invasive mechanical ventilation and in-hospital death) were analyzed.

Results: One hundred patients were included, 53% of whom were women. Median age was 59 years (interquartile range 44-70) and 66% were younger than 65. Seventy-five percent identified themselves as Black, despite representing 58% of hospitalized patients at our institution in 2019. Common comorbid conditions included hypertension (68%), obesity (65%), and diabetes mellitus (31%). Frequent clinical manifestations included shortness of breath (76%), cough (75%), and fever (64%). Symptoms were present for a median of 7 days (interquartile range 4-7) on presentation. Twenty-four percent of patients required mechanical ventilation and, overall, 19% died (67% of those requiring mechanical ventilation). Eighty-four percent of those who died were Black. On multivariate analysis, ever smoking (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.2-28.6) and history of diabetes mellitus (OR 5.9, 95% CI 1.5-24.3) were associated with mortality, and those admitted from home were less likely to die (vs outside facility, OR 0.2, 95% CI 0.0-0.7). Neither age, sex, race, body mass index, insurance status, nor rural residence was independently associated with mortality.

Conclusions: Our study adds evidence that Black patients appear to be overrepresented in those hospitalized with and those who die from COVID-19, likely a manifestation of adverse social determinants of health. These findings should help guide preventive interventions targeting groups at higher risk of acquiring and developing severe COVID-19 disease.
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http://dx.doi.org/10.14423/SMJ.0000000000001222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904045PMC
March 2021

EXPRESS: Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy for the Quantitative Analysis of Deuterium in Plasma: Application to Total Body Water Determination in Humans and Other Animals.

Authors:
Leigh Ward

Appl Spectrosc 2021 Feb 26:37028211002532. Epub 2021 Feb 26.

The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia, Brisbane, Queensland, Australia.

Conventional methods for measuring the concentration of deuterium in body fluids are by either isotope ratio mass spectrometry or Fourier transformed infra-red transmission (FTIR) spectroscopy. The latter method is often preferred as it is less expensive and time consuming; however, having a lower sensitivity means a larger sample volume is required. This study investigated an alternative FTIR spectroscopic method, attenuated total reflection Fourier transformed infra-red spectroscopy (ATR-FTIR), which has the potential to provide shorter analysis times while requiring smaller sample volumes. Deuterium was assayed by ATR-FTIR in plasma in the concentration range 0.5 to 2.5 mg mL-1, typical of those observed in tracer dilution measurements of total body water. Minimal sample preparation was required and analysis time was substantially decreased compared to transmission FTIR. Samples were analysed with high precision (CV < 0.5 %). Precision of assay was maintained when assaying plasma volumes of only 10 ï-L. The application of the method to the determination of total body water in humans and animals (horses) was demonstrated.A rapid and simple method for the measurement of deuterium in plasma is described that only requires very small sample volumes, rendering the method suitable for use in paediatrics where blood sampling is required to be kept to a minimum.
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http://dx.doi.org/10.1177/00037028211002532DOI Listing
February 2021

Importance of health assessments for conservation in noncaptive wildlife.

Conserv Biol 2021 Feb 25. Epub 2021 Feb 25.

College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, 4811, Australia.

Wildlife health assessments help identify populations at risk of starvation, disease, and decline from anthropogenic impacts on natural habitats. Here, we provide an overview of available health assessment studies in non-captive vertebrates, and propose a framework to strategically integrate health assessments in population monitoring. Using a systematic approach, we performed a thorough assessment of studies examining multiple health parameters of non-captive vertebrate species from 1982 to 2020 (n = 261). We quantified trends in study design and diagnostic methods across taxa. We found a spatial mismatch between biodiversity hotspots and study location. Only 35% of studies involved international or cross-border collaboration. IUCN Red List non-threatened species represented 49% of species assessed, a trend likely associated with the regional focus of most studies. We identified a critical need for using statistically adequate sample sizes for studies establishing reference ranges, and strongly suggest following strict protocols when planning the study design. The main health assessment methods used across all taxa were blood analysis (89%), body composition assessment methods (81%), physical examination (72%) and faecal analysis (24% of studies). Based on our findings, we propose a conceptual framework for improved design and standardization for quality wildlife health assessments. Integrating a physiological and ecological understanding of species resilience towards threatening processes will enable informed decision making regarding the conservation of threatened species. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/cobi.13724DOI Listing
February 2021

Partial biological and molecular characterization of a novel citrivirus from Nandina domestica.

Arch Virol 2021 Feb 23. Epub 2021 Feb 23.

Royal Horticultural Society (RHS), London, UK.

We report the complete genome sequence of a novel virus isolated from Nandina domestica 'Firepower' in Auckland, New Zealand. It was mechanically transmitted to Nicotiana species, although all of these infections were symptomless. The complete genome of the new virus is 8892 nucleotides (nt) long, excluding the 3' poly(A) tail, contains three open reading frames (ORF), and is most closely related to citrus leaf blotch virus (CLBV) Actinidia isolate (CLBV-Act; 72% nt sequence identity), a member of the genus Citrivirus. Replicase and coat proteins, encoded by genome ORFs 1 and 3 respectively, shared 81-83% and 76-79% amino acid (aa) sequence identity, respectively, with CLBV-Act. Computer-based analysis suggests that this novel virus is the result of recombination between CLBV-Act and an unknown virus, highlighting the importance of this phenomenon for betaflexivirus evolution.
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http://dx.doi.org/10.1007/s00705-020-04868-0DOI Listing
February 2021

Enabling deeper learning on big data for materials informatics applications.

Sci Rep 2021 Feb 19;11(1):4244. Epub 2021 Feb 19.

Department of Electrical and Computer Engineering, Northwestern University, Evanston, USA.

The application of machine learning (ML) techniques in materials science has attracted significant attention in recent years, due to their impressive ability to efficiently extract data-driven linkages from various input materials representations to their output properties. While the application of traditional ML techniques has become quite ubiquitous, there have been limited applications of more advanced deep learning (DL) techniques, primarily because big materials datasets are relatively rare. Given the demonstrated potential and advantages of DL and the increasing availability of big materials datasets, it is attractive to go for deeper neural networks in a bid to boost model performance, but in reality, it leads to performance degradation due to the vanishing gradient problem. In this paper, we address the question of how to enable deeper learning for cases where big materials data is available. Here, we present a general deep learning framework based on Individual Residual learning (IRNet) composed of very deep neural networks that can work with any vector-based materials representation as input to build accurate property prediction models. We find that the proposed IRNet models can not only successfully alleviate the vanishing gradient problem and enable deeper learning, but also lead to significantly (up to 47%) better model accuracy as compared to plain deep neural networks and traditional ML techniques for a given input materials representation in the presence of big data.
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http://dx.doi.org/10.1038/s41598-021-83193-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895970PMC
February 2021

Use of bioelectrical impedance spectroscopy to provide a measure of body composition in sows.

Animal 2020 Dec 29:100156. Epub 2020 Dec 29.

SunPork Group, Eagleview Place, Eagle Farm, Queensland, Australia.

The ability to accurately estimate fat mass and fat-free mass (FFM) has the potential to improve the way in which sow body condition can be managed in a breeding herd. Bioelectrical impedance spectroscopy (BIS) has been evaluated as a practical technique for assessment of body composition in several livestock species, but similar work is lacking in sows. Bioelectrical impedance uses population-specific algorithms that require values for the apparent resistivities of body fluids and body proportion factors. This study comprised three major aims: (i) to derive apparent resistivity coefficients for extracellular water (ECW) and intracellular water (ICW) required for validation of BIS predictions of total body water (TBW) in live sows against standard reference tracer dilution methods; (ii) to develop predictions of TBW to body composition prediction algorithms, namely FFM, by developing a body geometry correction factor (Kb) and (iii) to compare the BIS predictions of FFM against existing impedance predictors and published prediction equations for use in sows, based on physical measurements of back-fat depth and BW (P2-based predictors). Whole body impedance measurements and the determination of TBW by deuterium dilution and ECW by bromide dilution were performed on 40 Large White x Landrace sows. Mean apparent resistivity coefficients of body fluids were 431.1 Ω.cm for ECW and 1827.8 Ω.cm for ICW. Using these coefficients, TBW and ECW were over-estimated by 6.5 and 3.3%, respectively, compared to measured reference values, although these differences were not statistically different (P > 0.05). Mean Kb was 1.09 ± 0.14. Fat-free mass predictions were 194.9 kg, which equates to 60.9% of total sow weight, and 183.0 kg for BIS and the deuterium dilution method, respectively. Mean differences between the predicted and measured FFM values ranged from -8.2 to 32.7%, but were not statistically different (P > 0.05). Method validation (leave-one-out procedure) revealed that mean differences between predicted and measured values were not statistically significant (P > 0.05). Of the impedance-based predictors, equivalence testing revealed that BIS displayed the lowest test bias of 11.9 kg (8.2%), although the P2-based prediction equations exhibited the lowest bias and percentage equivalence, with narrow limits of agreement. Results indicate although differences between mean predicted and measured values were not significantly different, relatively wide limits of agreement suggest BIS as an impractical option for assessing body composition in individual sows compared to the use of existing prediction equations based on BW and back fat.
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http://dx.doi.org/10.1016/j.animal.2020.100156DOI Listing
December 2020

Bioelectrical impedance analysis for assessment of body composition in infants and young children-A systematic literature review.

Clin Obes 2021 Feb 9:e12441. Epub 2021 Feb 9.

Liggins Institute, University of Auckland, Auckland, New Zealand.

Bioelectrical impedance analysis (BIA) is an easy to use, portable tool, but the accuracy of the technique in infants and young children (<24 months) remains unclear. A systematic literature review was conducted to identify studies that have developed and validated BIA equations in this age group. MEDLINE, Scopus, EMBASE, and CENTRAL were searched for relevant literature published up until June 30, 2020, using terms related to bioelectrical impedance, body composition, and paediatrics. Two reviewers independently screened studies for eligibility, resulting in 15 studies that had developed and/or validated equations. Forty-six equations were developed and 34 validations were conducted. Most equations were developed in young infants (≤6 months), whereas only seven were developed among older infants and children (6-24 months). Most studies were identified as having a high risk of bias, and only a few included predominantly healthy children born at term. Using the best available evidence, BIA appears to predict body composition at least as well as other body composition tools; however, among younger infants BIA may provide little benefit over anthropometry-based prediction equations. Currently, none of the available equations can be recommended for use in research or in clinical practice.
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http://dx.doi.org/10.1111/cob.12441DOI Listing
February 2021

NICU-Specific Stress Following Traumatic Childbirth and Its Relationship With Posttraumatic Stress.

J Perinat Neonatal Nurs 2021 Jan-Mar 01;35(1):57-67

Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, Rhode Island (Drs Sharp and Ward); Women's Medicine Collaborative, The Miriam Hospital, Providence, Rhode Island (Dr Sharp); Department of Psychology, East Carolina University, Greenville, North Carolina (Ms Huber and Dr Dolbier); and Center for Behavioral and Preventative Medicine, The Miriam Hospital, Providence, Rhode Island (Dr Ward).

This mixed-methods pilot study investigated maternal perceived stress specific to infant neonatal intensive care unit (NICU) hospitalization as a moderator of the relationship between traumatic childbirth appraisal and symptoms of posttraumatic stress disorder (PTSD). NICU mothers (N = 77) were recruited via social media 1 to 4 months postpartum for a cross-sectional survey about perinatal experiences. Measures included traumatic childbirth, PTSD Checklist for DSM-5, and Parental Stressor Scale (PSS): NICU. Quantitative results indicated that, only at high levels of stress, women who reported traumatic childbirth (68%) reported significantly higher PTSD symptoms [b = 18.00, standard error = 7.18, t = 2.51, P = .015, 95% confidence interval (3.65, 32.36)]. Qualitative analysis identified additional stressors: maternal emotional well-being, dissatisfaction with care, infant health problems, breastfeeding, and additional characteristics of the NICU environment. Results provide supportive evidence that NICU mothers are at high risk for childbirth-related trauma and PTSD. Perceived stress related to the NICU may be an important intervention target when developing trauma-informed patient care. In addition to the domains captured by the PSS: NICU, maternal emotional well-being, interpersonal relationships with NICU staff, and stress related to breastfeeding are additional areas for improvement in the family-centered NICU.
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http://dx.doi.org/10.1097/JPN.0000000000000543DOI Listing
February 2021

Granick revisited: Synthesizing evolutionary and ecological evidence for the late origin of bacteriochlorophyll via ghost lineages and horizontal gene transfer.

PLoS One 2021 28;16(1):e0239248. Epub 2021 Jan 28.

Department of Plant Biology, University of California, Davis, California, United States of America.

Photosynthesis-both oxygenic and more ancient anoxygenic forms-has fueled the bulk of primary productivity on Earth since it first evolved more than 3.4 billion years ago. However, the early evolutionary history of photosynthesis has been challenging to interpret due to the sparse, scattered distribution of metabolic pathways associated with photosynthesis, long timescales of evolution, and poor sampling of the true environmental diversity of photosynthetic bacteria. Here, we reconsider longstanding hypotheses for the evolutionary history of phototrophy by leveraging recent advances in metagenomic sequencing and phylogenetics to analyze relationships among phototrophic organisms and components of their photosynthesis pathways, including reaction centers and individual proteins and complexes involved in the multi-step synthesis of (bacterio)-chlorophyll pigments. We demonstrate that components of the photosynthetic apparatus have undergone extensive, independent histories of horizontal gene transfer. This suggests an evolutionary mode by which modular components of phototrophy are exchanged between diverse taxa in a piecemeal process that has led to biochemical innovation. We hypothesize that the evolution of extant anoxygenic photosynthetic bacteria has been spurred by ecological competition and restricted niches following the evolution of oxygenic Cyanobacteria and the accumulation of O2 in the atmosphere, leading to the relatively late evolution of bacteriochlorophyll pigments and the radiation of diverse crown group anoxygenic phototrophs. This hypothesis expands on the classic "Granick hypothesis" for the stepwise evolution of biochemical pathways, synthesizing recent expansion in our understanding of the diversity of phototrophic organisms as well as their evolving ecological context through Earth history.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239248PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842958PMC
January 2021

Reconstitution of Human Necrosome Interactions in .

Biomolecules 2021 Jan 25;11(2). Epub 2021 Jan 25.

Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3083, Australia.

The necrosome is a large-molecular-weight complex in which the terminal effector of the necroptotic pathway, Mixed Lineage Kinase Domain-Like protein (MLKL), is activated to induce necroptotic cell death. The precise mechanism of MLKL activation by the upstream kinase, Receptor Interacting Serine/Threonine Protein Kinase 3 (RIPK3) and the role of Receptor Interacting Serine/Threonine Protein Kinase 1 (RIPK1) in mediating MLKL activation remain incompletely understood. Here, we reconstituted human necrosome interactions in yeast by inducible expression of these necrosome effectors. Functional interactions were reflected by the detection of phosphorylated MLKL, plasma membrane permeabilization, and reduced proliferative potential. Following overexpression of human necrosome effectors in yeast, MLKL aggregated in the periphery of the cell, permeabilized the plasma membrane and compromised clonogenic potential. RIPK1 had little impact on RIPK3/MLKL-mediated yeast lethality; however, it exacerbated the toxicity provoked by co-expression of MLKL with a RIPK3 variant bearing a mutated RHIM-domain. Small molecule necroptotic inhibitors necrostatin-1 and TC13172, and viral inhibitors M45 (residues 1-90) and BAV_Rmil, abated the yeast toxicity triggered by the reconstituted necrosome. This yeast model provides a convenient tool to study necrosome protein interactions and to screen for and characterize potential necroptotic inhibitors.
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http://dx.doi.org/10.3390/biom11020153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911209PMC
January 2021

Patient-Reported Outcomes from a Randomized, Active-Controlled, Open-Label, Phase 3 Trial of Burosumab Versus Conventional Therapy in Children with X-Linked Hypophosphatemia.

Calcif Tissue Int 2021 Jan 23. Epub 2021 Jan 23.

Department of Medicine and Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.

Changing to burosumab, a monoclonal antibody targeting fibroblast growth factor 23, significantly improved phosphorus homeostasis, rickets, lower-extremity deformities, mobility, and growth versus continuing oral phosphate and active vitamin D (conventional therapy) in a randomized, open-label, phase 3 trial involving children aged 1-12 years with X-linked hypophosphatemia. Patients were randomized (1:1) to subcutaneous burosumab or to continue conventional therapy. We present patient-reported outcomes (PROs) from this trial for children aged ≥ 5 years at screening (n = 35), using a Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire and SF-10 Health Survey for Children. PROMIS pain interference, physical function mobility, and fatigue scores improved from baseline with burosumab at weeks 40 and 64, but changed little with continued conventional therapy. Pain interference scores differed significantly between groups at week 40 (- 5.02, 95% CI - 9.29 to - 0.75; p = 0.0212) but not at week 64. Between-group differences were not significant at either week for physical function mobility or fatigue. Reductions in PROMIS pain interference and fatigue scores from baseline were clinically meaningful with burosumab at weeks 40 and 64 but not with conventional therapy. SF-10 physical health scores (PHS-10) improved significantly with burosumab at week 40 (least-squares mean [standard error] + 5.98 [1.79]; p = 0.0008) and week 64 (+ 5.93 [1.88]; p = 0.0016) but not with conventional therapy (between-treatment differences were nonsignificant). In conclusion, changing to burosumab improved PRO measures, with statistically significant differences in PROMIS pain interference at week 40 versus continuing with conventional therapy and in PHS-10 at weeks 40 and 64 versus baseline.Trial registration: ClinicalTrials.gov NCT02915705.
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http://dx.doi.org/10.1007/s00223-020-00797-xDOI Listing
January 2021

Phanerozoic radiation of ammonia oxidizing bacteria.

Sci Rep 2021 Jan 22;11(1):2070. Epub 2021 Jan 22.

Department of Plant Biology, University of California, Davis, Davis, CA, USA.

The modern nitrogen cycle consists of a web of microbially mediated redox transformations. Among the most crucial reactions in this cycle is the oxidation of ammonia to nitrite, an obligately aerobic process performed by a limited number of lineages of bacteria (AOB) and archaea (AOA). As this process has an absolute requirement for O, the timing of its evolution-especially as it relates to the Great Oxygenation Event ~ 2.3 billion years ago-remains contested and is pivotal to our understanding of nutrient cycles. To estimate the antiquity of bacterial ammonia oxidation, we performed phylogenetic and molecular clock analyses of AOB. Surprisingly, bacterial ammonia oxidation appears quite young, with crown group clades having originated during Neoproterozoic time (or later) with major radiations occurring during Paleozoic time. These results place the evolution of AOB broadly coincident with the pervasive oxygenation of the deep ocean. The late evolution AOB challenges earlier interpretations of the ancient nitrogen isotope record, predicts a more substantial role for AOA during Precambrian time, and may have implications for understanding of the size and structure of the biogeochemical nitrogen cycle through geologic time.
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http://dx.doi.org/10.1038/s41598-021-81718-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822890PMC
January 2021

Strengthening the U. S. Medication Safety Net by Connecting Abundance to Need.

J Health Care Poor Underserved 2020 ;31(2):503-518

Cost-related medication non-adherence (CRN) is a major population health concern in the United States, especially for patients with chronic conditions. It is associated with disease progression and increases the likelihood of emergency department utilization and hospitalization, thereby increasing overall health care expenditures. In this paper, we describe the prescription medication safety net in the United States and assess its reliability. We also introduce Dispensary of Hope (DoH), a charitable medication distribution network, as a reliable medication access program that is capable of filling gaps in medication coverage for low-income and uninsured Americans. Our critical assessment of the medication safety net in the United States suggests that an expansion of DoH could reduce CRN in the United States, improve chronic illness care, and help health systems achieve the triple aim of improving patient experiences and population health while reducing cost.
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http://dx.doi.org/10.1353/hpu.2020.0038DOI Listing
January 2020

Meet Me Where I Am: An Evaluation of an HIV Patient Navigation Intervention to Increase Uptake of PrEP Among Black Men Who Have Sex with Men in the Deep South.

J Racial Ethn Health Disparities 2021 Jan 5. Epub 2021 Jan 5.

John D. Bower School of Population Health, University of Mississippi Medical Center, 2500 North State Street, TR202-09, Jackson, MS, 39216, USA.

The southern region of the USA is the epicenter of the HIV epidemic. HIV disproportionately affects African Americans, particularly Black men who have sex with men (Black MSM). Given the alarming rates of new infections among Black MSM, there is an urgent need for culturally competent healthcare professionals who are trained to address the unique needs and barriers to uptake and adherence to HIV prevention, care, and treatment services. Utilizing a mixed method research approach, we conducted a process evaluation of Meet Me Where I Am, a 6-month, 6-session HIV/AIDS patient navigation training program for healthcare professionals and patient navigators working in organizations that provide HIV services to residents of central Mississippi, an area with high incidence and prevalence rates of HIV. A self-administered questionnaire after each session was given to participants to assess the acceptability, quality, and translational aspects of the training program. The overall positive feedback on the MMWIA training reflects the program's acceptability and feasibility. Participants found that the training was effective in providing the necessary knowledge and skills to deliver patient-centered HIV prevention-related navigation services. A majority (67%) of participants indicated that they felt they could apply the lessons learned within their healthcare settings to improve access to HIV prevention, care, and treatment services. If we are to reduce racial and ethnic disparities in HIV/AIDS, there is a critical need for culturally appropriate training programs designed to improve the ability of healthcare professionals and health systems to deliver culturally competent HIV prevention, care, and treatment services.
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http://dx.doi.org/10.1007/s40615-020-00933-1DOI Listing
January 2021

Glucocorticoid-Induced Osteoporosis: Why Kids Are Different.

Authors:
Leanne M Ward

Front Endocrinol (Lausanne) 2020 16;11:576. Epub 2020 Dec 16.

The Ottawa Pediatric Bone Health Research Group, The Children's Hospital of Eastern Ontario Genetic and Metabolic Bone Disease Clinic, University of Ottawa, Ottawa, ON, Canada.

Glucocorticoids (GC) are an important risk factor for bone fragility in children with serious illnesses, largely due to their direct adverse effects on skeletal metabolism. To better appreciate the natural history of fractures in this setting, over a decade ago the Canadian eroid-associated steoporosis in the ediatric opulation ("") Consortium launched a 6 year, multi-center observational cohort study in GC-treated children. This study unveiled numerous key clinical-biological principles about GC-induced osteoporosis (GIO), many of which are unique to the growing skeleton. This was important, because most GIO recommendations to date have been guided by adult studies, and therefore do not acknowledge the pediatric-specific principles that inform monitoring, diagnosis and treatment strategies in the young. Some of the most informative observations from the STOPP study were that vertebral fractures are the hallmark of pediatric GIO, they occur early in the GC treatment course, and they are frequently asymptomatic (thereby undetected in the absence of routine monitoring). At the same time, some children have the unique, growth-mediated ability to restore normal vertebral body dimensions following vertebral fractures. This is an important index of recovery, since spontaneous vertebral body reshaping may preclude the need for osteoporosis therapy. Furthermore, we now better understand that children with poor growth, older children with less residual growth potential, and children with ongoing bone health threats have less potential for vertebral body reshaping following spine fractures, which can result in permanent vertebral deformity if treatment is not initiated in a timely fashion. Therefore, pediatric GIO management is now predicated upon early identification of vertebral fractures in those at risk, and timely intervention when there is limited potential for spontaneous recovery. A single, low-trauma long bone fracture can also signal an osteoporotic event, and a need for treatment. Intravenous bisphosphonates are currently the recommended therapy for pediatric GC-induced bone fragility, typically prescribed to children with limited potential for medication-unassisted recovery. It is recognized, however, that even early identification of bone fragility, combined with timely introduction of intravenous bisphosphonate therapy, may not completely rescue the osteoporosis in those with the most aggressive forms, opening the door to novel strategies.
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http://dx.doi.org/10.3389/fendo.2020.00576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772619PMC
December 2020

First-Day Use of the Newborn Weight Loss Tool to Predict Excess Weight Loss in Breastfeeding Newborns.

Breastfeed Med 2021 Mar 18;16(3):230-237. Epub 2020 Dec 18.

Department of Rehabilitation, Exercise, and Nutritional Sciences, College of Allied Health Sciences, University of Cincinnati, Cincinnati, Ohio, USA.

Exclusive breastfeeding is recommended for most newborns. However, exclusively breastfed newborns sometimes experience excess weight loss (EWL, loss ≥10% of birth weight) while lactation is being established. Our primary objective was to evaluate the sensitivity and specificity of the Newborn Weight Loss Tool (NEWT) in early identification of exclusively breastfed newborns who develop EWL; and secondarily, identify breastfeeding variables associated with an at-risk NEWT trajectory. We conducted a secondary analysis of prospective data from mother-infant dyads screened for inclusion in the U.S. site of the WHO Growth Reference Study. We excluded records if: NEWT-specific criteria not met, missing key data, or >60 mL formula consumed. We defined NEWT "test-positive" based on an in-hospital weight at about 24 hours falling within the NEWT trajectory consistent with eventual EWL. We defined cases as true EWL based on weight measured at home on day of life 4 (DoL4). Of 280 original records, 60 were excluded ( = 27, NEWT-specific exclusion;  = 15, missing data;  = 18, >60 mL formula), resulting in 220 paired newborn weights measured in-hospital (17 ± 8 hours), and at DoL4 (84 ± 8 hours). NEWT status correctly identified 6/28 EWL cases (21% sensitivity [95% confidence interval, CI, 8-34%]), and 158/192 noncases (82% specificity [95% CI, 75-89%]). NEWT test-positive status was associated with greater weight loss, lower perceived breastfeeding support, and infant less often showing feeding cues on DoL4 ( < 0.05). Sensitivity in predicting EWL is low when applying NEWT at about 24 hours of life; however, early test-positive status is associated with indicators of breastfeeding difficulties on DoL4.
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http://dx.doi.org/10.1089/bfm.2020.0280DOI Listing
March 2021

Differential diagnosis of vergence and saccade disorders in dyslexia.

Sci Rep 2020 12 17;10(1):22116. Epub 2020 Dec 17.

IRIS Lab, Neurophysiology of Binocular Motor Control and Vision, CNRS FRE2022 Neurosciences, UFR Biomedical, University of Paris, 45 rue des Saints Pères, 75006, Paris, France.

Previous studies suggest vergence and saccade abnormalities in dyslexic adolescents. However, these studies are mainly clinically based and do not provide objective measurements of eye movements, but rather subjectively evaluate vergence using haplosopic conditions in which the two eyes are dissociated (via polarizers, prisms, or intermittent spectacles). Other studies have identified deficits with binocular coordination during reading in dyslexics. Yet, there are few studies that provide objective measurements of eye movements in the dyslexic population to help provide more information regarding if these deficits could be due to an intrinsic motor problem or if they are the consequence of poor reading. 47 dyslexic adolescents (18 female, 29 male; mean age 15.5) and 44 non-dyslexic adolescents (22 female, 22 male; mean age 14.8) wore a head-based eye tracker (PupilCore, Pupil Labs, Berlin) which recorded wide angle saccade and vergence eye movements at 200 Hz. Tests were run using the REMOBI device, which produced a saccade or vergence audiovisual target. Analysis of eye movements was performed with lab-developed software, AIDEAL. The results showed statistically significant abnormalities in vergence and saccades. In vergence, dyslexics displayed a reduced amplitude of the visually driven portion of convergence and a longer duration in the initial phase of divergence. In saccades, dyslexic adolescents demonstrated slower saccades in both directions. They also had an increased disconjugate drift in the first 80 or 160 ms following saccades to the right, suggesting poor binocular coordination. For both vergence and saccades, the peak velocity and time to peak velocity was higher and earlier, respectively, in non-dyslexics compared to dyslexics; yet the average velocity of both movements was lower in dyslexics. Thus, these results indicate peculiar velocity profiles in dyslexics, particularly a slow deceleration phase in both vergence and saccades. The study provides an objective method to diagnose vergence and saccade abnormalities while viewing targets in the real three-dimensional space in a dyslexic population. Vergence abnormalities are demonstrated to be a problem in dyslexics, occurring independently from reading. We hypothesize these disconjugate drifts following saccades are the result of slow vergence capacity. Rehabilitation programs, such as those using REMOBI, should aim to target these deficits in vergence velocity, as this has been shown to improve binocular control.
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http://dx.doi.org/10.1038/s41598-020-79089-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747706PMC
December 2020

Development of a Quality Improvement Learning Collaborative to Improve Pediatric Sepsis Outcomes.

Pediatrics 2021 Jan 16;147(1). Epub 2020 Dec 16.

Pediatric Infectious Diseases, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota.

Pediatric sepsis is a major public health problem. Published treatment guidelines and several initiatives have increased adherence with guideline recommendations and have improved patient outcomes, but the gains are modest, and persistent gaps remain. The Children's Hospital Association Improving Pediatric Sepsis Outcomes (IPSO) collaborative seeks to improve sepsis outcomes in pediatric emergency departments, ICUs, general care units, and hematology/oncology units. We developed a multicenter quality improvement learning collaborative of US children's hospitals. We reviewed treatment guidelines and literature through 2 in-person meetings and multiple conference calls. We defined and analyzed baseline sepsis-attributable mortality and hospital-onset sepsis and developed a key driver diagram (KDD) on the basis of treatment guidelines, available evidence, and expert opinion. Fifty-six hospital-based teams are participating in IPSO; 100% of teams are engaged in educational and information-sharing activities. A baseline, sepsis-attributable mortality of 3.1% was determined, and the incidence of hospital-onset sepsis was 1.3 cases per 1000 hospital admissions. A KDD was developed with the aim of reducing both the sepsis-attributable mortality and the incidence of hospital-onset sepsis in children by 25% from baseline by December 2020. To accomplish these aims, the KDD primary drivers focus on improving the following: treatment of infection; recognition, diagnosis, and treatment of sepsis; de-escalation of unnecessary care; engagement of patients and families; and methods to optimize performance. IPSO aims to improve sepsis outcomes through collaborative learning and reliable implementation of evidence-based interventions.
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http://dx.doi.org/10.1542/peds.2020-1434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874527PMC
January 2021

A practical contemporary approach to decision-making on subclinical hypothyroidism.

Arch Endocrinol Metab 2020 Dec 15. Epub 2020 Dec 15.

Laboratório de Genética Molecular do Câncer, Faculdade de Ciências Médicas (FCM), Universidade Estadual de Campinas (Unicamp), Campinas, SP, Brasil.

Subclinical hypothyroidism (Shypo) is an increasingly frequent condition in common medical practice. Its diagnosis continues to pose a challenge since a series of non-thyroidal and temporary conditions can elevate serum TSH levels. In addition, the consequences of Shypo are still up for debate. Although detrimental cardiovascular effects have been consistently demonstrated in the young, they are less evident in older adults (65-79 years), and even more so in the oldest old (≥80 years). In the absence of evidence of any benefits of treating Shypo in patients' clinical manifestations and unfavorable outcomes, the most effective decision-making approach should include a thorough investigation of the patient's condition integrating all relevant clinical data, such as TSH levels, age, quality of life, comorbidities, cardiovascular risk, safety, and personal preferences. The decision-making process needs to take into account the risk of levothyroxine overtreatment and the resulting adverse consequences, such as reduction of bone mineral density, heart failure, and atrial fibrillation. Hence, current evidence suggests that individuals with TSH > 10 mU/L, who test positive for TPO Ab or are symptomatic may benefit from levothyroxine treatment. However, a more cautious and conservative approach is required in older (≥65 years of age), and oldest-old (≥80 years) patients, particularly those with frailty, in which the risk of treatment can outweigh potential benefits. The latter may benefit from a wait-and-see approach.
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http://dx.doi.org/10.20945/2359-3997000000317DOI Listing
December 2020

Beyond Objectification: Understanding the Correlates and Consequences of Sexualization for Black and White Adolescent Girls.

J Res Adolesc 2020 Dec 10. Epub 2020 Dec 10.

Teachers College, Columbia University, USA.

Although objectification theory posits negative consequences of self-objectification for adolescent girls, few studies have tested how objectification and sexualization contribute to mental health for youth of color. Accordingly, the current study explores the relations among body surveillance, enjoyment of sexualization, and mental health for a sample of 473 Black and White adolescent girls (Mage = 15.21, SD = 1.43). As expected, body surveillance and enjoyment of sexualization were associated with various forms of diminished well-being. Race moderated two of these links, with Black girls who reported higher levels of body surveillance also reporting higher levels of depression and hostility compared with their White peers. Future work should examine the implications of enjoyment of sexualization for youth of color.
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http://dx.doi.org/10.1111/jora.12598DOI Listing
December 2020

Three Decades of Bioelectrical Impedance Spectroscopy in Lymphedema Assessment: An Historical Perspective.

Lymphat Res Biol 2020 Nov 25. Epub 2020 Nov 25.

School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.

Bioelectrical impedance spectroscopy (BIS) is a technology that is widely used for the assessment of body composition. The method is based on the measurement of the electrical resistance of the body or a body region that can be quantitatively related to the amount of water in the tissues. Lymphedema is characterized, at least in its early stages, as an accumulation of lymph, an extracellular fluid. In the late 1980s, it was recognized that it might be possible to adapt BIS protocols to measure this increase in lymph volume. Subsequently, the use of BIS for the early detection of breast cancer-related lymphedema was demonstrated in the early 1990s, with BIS reference values indicative of lymphedema published in 2001. The subsequent two decades have seen BIS become a widely accepted method for lymphedema assessment. This review traces the evolution of the BIS technique since its inception and presents the current state of the art, with particular emphasis on utility in clinical practice.
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http://dx.doi.org/10.1089/lrb.2020.0085DOI Listing
November 2020

Acute Cervical Radiculopathy Outcomes: Soft Disc Herniations vs Osteophytes.

Pain Med 2020 Nov 23. Epub 2020 Nov 23.

Emory University, Emory Spine Center, Atlanta, Georgia,USA.

Objective: Prospectively evaluate the clinical outcomes of acute cervical radiculopathy with respect to soft disc herniations vs osteophytes.

Methods: Sixty consecutive patients who had had cervical radiculopathy for ≤1 month were enrolled in the study. Inclusion criteria were radicular pain greater than axial pain and a pain score ≥4 out of 10 on a numerical rating scale. Patients had at least one positive clinical finding: motor, sensory, or reflex changes. Plain films and magnetic resonance imaging were ordered. Follow-up was at 6 weeks and 3, 6, and 12 months. Outcomes included pain scores (neck and upper limb), neck disability index, medication use, opioid use, and need for surgery. Two attending musculoskeletal radiologists reviewed imaging findings for osteophytes vs soft disc herniations at the symptomatic level.

Results: More than 75% reduction in pain was seen in 77% of patients with soft disc herniations and 66% of patients with osteophytes (P > 0.05) at 12 months. A pain score ≤2 out of 10 within 6 to 12 months was seen in 86% of patients with soft disc herniations and 81% of patients with osteophytes (P > 0.05). Moderate or marked improvement at 12 months was seen in 85% of patients with soft discs and 77% of patients with osteophytes (P > 0.05). Baseline-to-12-month numerical rating scale pain scores of patients with soft discs vs osteophytes had overlapping confidence intervals at each follow-up. At 12 months, very few had undergone surgery (7% of patients with soft discs, 11% of patients with osteophytes; P > 0.05) or were on opioids (7% of patients with soft discs, 9% of patients with osteophytes; P > 0.05).

Conclusions: The majority of patients, but not all patients, with acute radiculopathies improved with time. This was seen with both soft disc herniations and osteophytes.
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http://dx.doi.org/10.1093/pm/pnaa341DOI Listing
November 2020

Warped rhythms: Epileptic activity during critical periods disrupts the development of neural networks for human communication.

Behav Brain Res 2021 Feb 16;399:113016. Epub 2020 Nov 16.

University of British Columbia, Department of Psychology, 2136 West Mall, Vancouver BC V6T 1Z4, Canada; University of British Columbia, Djavad Mowafaghian Centre for Brain Health, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada.

It is well established that temporal lobe epilepsy-the most common and well-studied form of epilepsy-can impair communication by disrupting social-emotional and language functions. In pediatric epilepsy, where seizures co-occur with the development of critical brain networks, age of onset matters: The earlier in life seizures begin, the worse the disruption in network establishment, resulting in academic hardship and social isolation. Yet, little is known about the processes by which epileptic activity disrupts developing human brain networks. Here we take a synthetic perspective-reviewing a range of research spanning studies on molecular and oscillatory processes to those on the development of large-scale functional networks-in support of a novel model of how such networks can be disrupted by epilepsy. We seek to bridge the gap between research on molecular processes, on the development of human brain circuitry, and on clinical outcomes to propose a model of how epileptic activity disrupts brain development.
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http://dx.doi.org/10.1016/j.bbr.2020.113016DOI Listing
February 2021

Impact of Institutional Breastfeeding Support in Very Low-Birth Weight Infants.

Breastfeed Med 2021 Mar 18;16(3):238-244. Epub 2020 Nov 18.

Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Feeding of human milk is associated with improved health outcomes in preterm infants. Mothers of preterm infants have difficulty establishing and maintaining an adequate milk supply. Our institution participated in Best Fed Beginnings (BFB), a national breastfeeding quality improvement collaborative, in 2012. Although most practice changes targeted healthy term infants, we hypothesized that mother's milk feeding (MMF) to preterm infants would also improve. Our objective was to compare MMF in very low-birth weight (VLBW) infants at discharge before and after our participation in BFB. We completed a retrospective chart review of VLBW infants born between January 2006 and June 2016. The primary outcome measure was the percentage of VLBW infants receiving MMF at hospital discharge. We used Fisher's exact test to determine the difference before and after 2012 and performed the Kruskal-Wallis test to determine changes in median time to pump initiation in mothers of VLBW infants. Multiple logistic regression was used to determine variables associated with the primary outcome. A total of 1,077 VLBW infants were eligible. After launching BFB, MMF at discharge increased in VLBW infants, from 35.2% to 46.0%,  < 0.001. Median time to pump initiation decreased from 11 to 5 hours after 2012,  = 0.0001. Factors significantly associated with receiving MMF at discharge included birth post-BFB; private insurance; non-Black race; shorter length of stay; older maternal age; and mother's milk as first feeding. Hospital culture supportive of breastfeeding impacts not only healthy term infants but also VLBW infants. Earlier initiation of milk expression significantly improves provision of MMF to preterm infants at discharge.
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http://dx.doi.org/10.1089/bfm.2020.0137DOI Listing
March 2021

Resistance training decreases plasma levels of adipokines in postmenopausal women.

Sci Rep 2020 11 16;10(1):19837. Epub 2020 Nov 16.

Department of Obstetrics and Gynaecology in Linköping, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Physical inactivity and the onset of menopause increase the risk of cardiovascular disease amongst postmenopausal women. We aim to investigate the effect of resistance training (RT) on plasma levels of selected cytokines, adipokines, myokines, and sex hormones in postmenopausal women with vasomotor symptoms. This was a sub-study of a randomised controlled trial investigating the effects of RT on vasomotor symptoms in postmenopausal women. Women were randomised to join a 15-week RT program (n = 26) or remain sedentary as control (n = 29). Venous blood samples were taken at week-0 and week-15 for all participants. Enzyme-linked immunosorbent assays and multiple bead assays were used to measure cytokines, adipokines, myokines, and sex hormones in plasma. Plasma measurements of 16 of 33 analytes were within detectable limits. After adjusting for good compliance in the RT group (58% of RT participants), after 15 weeks, significantly lower plasma levels of adiponectin (p < 0.001), lipocalin-2 (p < 0.01) and resistin (p = 0.04) were found. Comparing control and RT women, using change-over-time values, significant increases in median testosterone and sex hormone binding globulin levels were seen in RT women. RT intervention lowers the levels of adipokines, particularly adiponectin, in postmenopausal women with vasomotor symptoms. These results were secondary outcomes of a clinical trial, and further investigations in a larger cohort are essential with the additional control of diet control and body composition analyses. Nevertheless, our study shows RT may be a beneficial intervention in reducing inflammation amongst postmenopausal women.
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http://dx.doi.org/10.1038/s41598-020-76901-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669850PMC
November 2020

Chronic white matter changes detected using diffusion tensor imaging following adult traumatic brain injury and their relationship to cognition.

Neuropsychology 2020 Nov;34(8):881-893

Australian E-Health Research Centre, CSIRO.

White matter (WM) changes detected using diffusion tensor imaging (DTI) are reportedly related to cognitive outcomes following traumatic brain injury (TBI), but much existing research is underpowered or has only examined general outcomes, rather than cognitive functioning. A large sample of adults who had sustained mild, moderate or severe TBIs seven months prior ( = 165) and a control group ( = 106) underwent DTI and cognitive testing. Fractional anisotropy and mean diffusivity were calculated for 5 regions (corpus callosum: genu, body, splenium; fornix; superior longitudinal fasciculus) that recent meta-analyses identified as being affected by TBI and related to cognition following TBI. Memory, attention and executive functioning, which are often affected by TBI, were assessed. Overall, mild TBI did not show significant WM or cognitive changes, relative to controls, but moderate to severe TBI was associated with large WM alterations (all regions) and poorer cognitive performance. No significant correlations were found between DTI findings and cognition in the moderate to severe group. The findings have shown that moderate to severe TBI leads to considerable WM and cognitive changes. Early and ongoing examination of mild TBI is needed to determine whether WM and cognitive changes are initially present and, if so, when they resolve. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/neu0000690DOI Listing
November 2020

Saliva collected in universal transport media is an effective, simple and high-volume amenable method to detect SARS-CoV-2.

Clin Microbiol Infect 2020 Nov 4. Epub 2020 Nov 4.

Alberta Public Health Laboratory, Alberta Precision Laboratories, Calgary, Canada; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada.

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http://dx.doi.org/10.1016/j.cmi.2020.10.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641592PMC
November 2020

Standardization of lower extremity quantitative lymphedema measurements and associated patient-reported outcomes in gynecologic cancers.

Gynecol Oncol 2021 Feb 4;160(2):625-632. Epub 2020 Nov 4.

National Cancer Institute, Division of Cancer Prevention, 9609 Medical Center Drive, Rockville, MD 20892-9785, USA. Electronic address:

Practice changing standardization of lower extremity lymphedema quantitative measurements with integrated patient reported outcomes will likely refine and redefine the optimal risk-reduction strategies to diminish the devastating limb-related dysfunction and morbidity associated with treatment of gynecologic cancers. The National Cancer Institute (NCI), Division of Cancer Prevention brought together a diverse group of cancer treatment, therapy and patient reported outcomes experts to discuss the current state-of-the-science in lymphedema evaluation with the potential goal of incorporating new strategies for optimal evaluation of lymphedema in future developing gynecologic clinical trials.
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http://dx.doi.org/10.1016/j.ygyno.2020.10.026DOI Listing
February 2021