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1.
medRxiv ; 2024 May 03.
Article in English | MEDLINE | ID: mdl-38746428

ABSTRACT

Background: HIV status awareness and linkage to care are critical for ending the HIV epidemic and preventing tuberculosis (TB). Among household contacts of persons with TB, HIV greatly increases the risk of incident TB and death. However, almost half of household contacts in routine settings decline HIV test offers during routine contact investigation. We evaluated a brief social-behavioral norming intervention to increase acceptance of HIV testing during household TB contact investigation. Methods: We carried out a household-randomized, controlled trial to evaluate the effect of the norming strategy among household contacts of persons with pulmonary TB in Kampala, Uganda ( ClinicalTrials.gov # NCT05124665 ). Community health workers (CHW) visited homes of persons with TB to screen contacts for TB symptoms and offer free, optional, oral HIV testing. Households were randomized (1:1) to usual care or the norming strategy. Contacts were eligible if they were ≥ 15 years old, self-reported to be HIV-negative, and living in a multi-contact household. The primary outcome, the proportion of contacts accepting HIV testing, was analyzed using an intention-to-treat approach, using a mixed-effects model to account for clustering by household. We assessed HIV testing yield as a proportion of all contacts tested. Results: We randomized 328 contacts in 99 index households to the norming strategy, of whom 285 (87%) contacts were eligible. We randomized 224 contacts in 86 index households to the usual strategy, of whom 187 (84%) contacts were eligible. Acceptance of HIV testing was higher in the intervention arm (98% versus 92%, difference +6%, 95%CI +2% to +10%, p=0.004). Yield of HIV testing was 2.1% in the intervention arm and 0.6% in the control arm (p=0.22). Conclusion: A norming intervention significantly improved uptake of HIV testing among household contacts of persons with TB. Funding/Support: This work was supported by the Center for Interdisciplinary Research on AIDS (P30MH062294) and the Fogarty International Center of the National Institutes of Health (R21TW011270). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other sponsors.

2.
GigaByte ; 2024: gigabyte118, 2024.
Article in English | MEDLINE | ID: mdl-38746537

ABSTRACT

Marsupials exhibit distinctive modes of reproduction and early development that set them apart from their eutherian counterparts and render them invaluable for comparative studies. However, marsupial genomic resources still lag far behind those of eutherian mammals. We present a series of novel genomic resources for the fat-tailed dunnart (Sminthopsis crassicaudata), a mouse-like marsupial that, due to its ease of husbandry and ex-utero development, is emerging as a laboratory model. We constructed a highly representative multi-tissue de novo transcriptome assembly of dunnart RNA-seq reads spanning 12 tissues. The transcriptome includes 2,093,982 assembled transcripts and has a mammalian transcriptome BUSCO completeness score of 93.3%, the highest amongst currently published marsupial transcriptomes. This global transcriptome, along with ab initio predictions, supported annotation of the existing dunnart genome, revealing 21,622 protein-coding genes. Altogether, these resources will enable wider use of the dunnart as a model marsupial and deepen our understanding of mammalian genome evolution.

3.
Proc Natl Acad Sci U S A ; 121(21): e2320384121, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38743620

ABSTRACT

A recent advance in the study of emergent magnetic monopoles was the discovery that monopole motion is restricted to dynamical fractal trajectories [J. N. Hallén et al., Science 378, 1218 (2022)], thus explaining the characteristics of magnetic monopole noise spectra [R. Dusad et al., Nature 571, 234 (2019); A. M. Samarakoon et al., Proc. Natl. Acad. Sci. U.S.A. 119, e2117453119 (2022)]. Here, we apply this novel theory to explore the dynamics of field-driven monopole currents, finding them composed of two quite distinct transport processes: initially swift fractal rearrangements of local monopole configurations followed by conventional monopole diffusion. This theory also predicts a characteristic frequency dependence of the dissipative loss angle for AC field-driven currents. To explore these novel perspectives on monopole transport, we introduce simultaneous monopole current control and measurement techniques using SQUID-based monopole current sensors. For the canonical material Dy2Ti2O7, we measure [Formula: see text], the time dependence of magnetic flux threading the sample when a net monopole current [Formula: see text] is generated by applying an external magnetic field [Formula: see text] These experiments find a sharp dichotomy of monopole currents, separated by their distinct relaxation time constants before and after t ~[Formula: see text] from monopole current initiation. Application of sinusoidal magnetic fields [Formula: see text] generates oscillating monopole currents whose loss angle [Formula: see text] exhibits a characteristic transition at frequency [Formula: see text] over the same temperature range. Finally, the magnetic noise power is also dichotomic, diminishing sharply after t ~[Formula: see text]. This complex phenomenology represents an unprecedented form of dynamical heterogeneity generated by the interplay of fractionalization and local spin configurational symmetry.

4.
PLOS Glob Public Health ; 4(5): e0002609, 2024.
Article in English | MEDLINE | ID: mdl-38696500

ABSTRACT

Household-based tuberculosis (TB) contact evaluation may be an efficient strategy to reach people who could benefit from oral pre-exposure prophylaxis (PrEP) because of the epidemiological links between HIV and TB. This study estimated the number of HIV serodifferent couples in TB-affected households and potential HIV acquisitions averted through their PrEP use in 4 TB-HIV high-burden countries. We conducted a model-based analysis set in Ethiopia, Kenya, South Africa, and Uganda using parameters from population-based household surveys, systematic literature review and meta-analyses, and estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. We parameterized the nonlinear relationship between the proportion of serodifferent couples among people living with HIV and population-level HIV prevalence using Markov chain Monte Carlo methods. We integrated all parameters in a mathematical model and propagated uncertainty using a Monte Carlo approach. We estimated the HIV prevalence among adults aged 15-49 living in TB-affected households to be higher than in the general population in all 4 countries. The proportion of serodifferent couples among all couples in TB-affected households was also higher than in the general population (South Africa: 20.7% vs. 15.7%, Kenya: 15.7% vs. 5.7%, Uganda: 14.5% vs. 6.0%, Ethiopia: 4.1% vs. 0.8%). We estimated that up to 1,799 (95% UI: 1,256-2,341) HIV acquisitions in South Africa could be prevented annually by PrEP use in serodifferent couples in TB-affected households, 918 (95% UI: 409-1,450) in Kenya, 686 (95% UI: 505-871) in Uganda, and 408 (95% UI: 298-522) in Ethiopia. As couples in TB-affected households are more likely to be serodifferent than couples in the general population, offering PrEP during household TB contact evaluation may prevent a substantial number of HIV acquisitions.

6.
Auton Neurosci ; 253: 103175, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38677130

ABSTRACT

Social stress is a major risk factor for comorbid conditions including cardiovascular disease and depression. While women exhibit 2-3× the risk for these stress-related disorders compared to men, the mechanisms underlying heightened stress susceptibility among females remain largely unknown. Due to a lack in understanding of the pathophysiology underlying stress-induced comorbidities among women, there has been a significant challenge in developing effective therapeutics. Recently, a causal role for inflammation has been established in the onset and progression of comorbid cardiovascular disease/depression, with women exhibiting increased sensitivity to stress-induced immune signaling. Importantly, reduced vagal tone is also implicated in stress susceptibility, through a reduction in the vagus nerve's well-recognized anti-inflammatory properties. Thus, examining therapeutic strategies that stabilize vagal tone during stress may shed light on novel targets for promoting stress resilience among women. Recently, accumulating evidence has demonstrated that physical activity exerts cardio- and neuro-protective effects by enhancing vagal tone. Based on this evidence, this mini review provides an overview of comorbid cardiovascular and behavioral dysfunction in females, the role of inflammation in these disorders, how stress may impart its negative effects on the vagus nerve, and how exercise may act as a preventative. Further, we highlight a critical gap in the literature with regard to the study of females in this field. This review also presents novel data that are the first to demonstrate a protective role for voluntary wheel running over vagal tone and biomarkers of cardiac dysfunction in the face of social stress exposure in female rats.

7.
Genome Biol ; 25(1): 94, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622708

ABSTRACT

Recent innovations in single-cell RNA-sequencing (scRNA-seq) provide the technology to investigate biological questions at cellular resolution. Pooling cells from multiple individuals has become a common strategy, and droplets can subsequently be assigned to a specific individual by leveraging their inherent genetic differences. An implicit challenge with scRNA-seq is the occurrence of doublets-droplets containing two or more cells. We develop Demuxafy, a framework to enhance donor assignment and doublet removal through the consensus intersection of multiple demultiplexing and doublet detecting methods. Demuxafy significantly improves droplet assignment by separating singlets from doublets and classifying the correct individual.


Subject(s)
Single-Cell Analysis , Humans , Single-Cell Analysis/methods , Sequence Analysis, RNA/methods
8.
Sci Data ; 11(1): 349, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38589396

ABSTRACT

The Caribbean & Mesoamerica Biogeochemical Isotope Overview (CAMBIO) is an archaeological data community designed to integrate published biogeochemical data from the Caribbean, Mesoamerica, and southern Central America to address questions about dynamic interactions among humans, animals, and the environment in the region over the past 10,000 years. Here we present the CAMBIO human dataset, which consists of more than 16,000 isotopic measurements from human skeletal tissue samples (δ13C, δ15N, δ34S, δ18O, 87Sr/86Sr, 206/204Pb, 207/204Pb, 208/204Pb, 207/206Pb) from 290 archaeological sites dating between 7000 BC to modern times. The open-access dataset also includes detailed chronological, contextual, and laboratory/sample preparation information for each measurement. The collated data are deposited on the open-access CAMBIO data community via the Pandora Initiative data platform ( https://pandoradata.earth/organization/cambio ).


Subject(s)
Archaeology , Isotopes , Lead , Animals , Humans , Caribbean Region , Central America
9.
Phys Rev Lett ; 132(15): 152503, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38682970

ABSTRACT

The first complete measurement of the ß-decay strength distribution of _{17}^{45}Cl_{28} was performed at the Facility for Rare Isotope Beams (FRIB) with the FRIB Decay Station Initiator during the second FRIB experiment. The measurement involved the detection of neutrons and γ rays in two focal planes of the FRIB Decay Station Initiator in a single experiment for the first time. This enabled an analytical consistency in extracting the ß-decay strength distribution over the large range of excitation energies, including neutron unbound states. We observe a rapid increase in the ß-decay strength distribution above the neutron separation energy in _{18}^{45}Ar_{27}. This was interpreted to be caused by the transitioning of neutrons into protons excited across the Z=20 shell gap. The SDPF-MU interaction with reduced shell gap best reproduced the data. The measurement demonstrates a new approach that is sensitive to the proton shell gap in neutron rich nuclei according to SDPF-MU calculations.

10.
Nat Genet ; 56(4): 595-604, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38548990

ABSTRACT

Common genetic variants confer substantial risk for chronic lung diseases, including pulmonary fibrosis. Defining the genetic control of gene expression in a cell-type-specific and context-dependent manner is critical for understanding the mechanisms through which genetic variation influences complex traits and disease pathobiology. To this end, we performed single-cell RNA sequencing of lung tissue from 66 individuals with pulmonary fibrosis and 48 unaffected donors. Using a pseudobulk approach, we mapped expression quantitative trait loci (eQTLs) across 38 cell types, observing both shared and cell-type-specific regulatory effects. Furthermore, we identified disease interaction eQTLs and demonstrated that this class of associations is more likely to be cell-type-specific and linked to cellular dysregulation in pulmonary fibrosis. Finally, we connected lung disease risk variants to their regulatory targets in disease-relevant cell types. These results indicate that cellular context determines the impact of genetic variation on gene expression and implicates context-specific eQTLs as key regulators of lung homeostasis and disease.


Subject(s)
Pulmonary Fibrosis , Quantitative Trait Loci , Humans , Quantitative Trait Loci/genetics , Pulmonary Fibrosis/genetics , Gene Expression Regulation/genetics , Lung , Multifactorial Inheritance , Genome-Wide Association Study/methods , Polymorphism, Single Nucleotide
11.
Open Forum Infect Dis ; 11(3): ofae033, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38456193

ABSTRACT

Background: Preserved ratio impaired spirometry (PRISm), defined as a normal ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (≥0.70) with low FEV1 (<80% predicted), has been associated with increased mortality in the general population. Female sex has been associated with increased odds of PRISm in people without HIV. People with HIV (PWH) are at increased risk for lung function abnormalities, but whether HIV modifies the effect of sex on PRISm development is largely unknown. Methods: Adults with and without HIV underwent baseline followed by serial spirometry after completing therapy for pneumonia, predominantly tuberculosis (TB), in Kampala, Uganda. Using generalized estimating equations adjusted for age, body mass index, smoking, biomass fuel exposure, HIV, and TB status, we compared individuals with PRISm with those with normal spirometry. These models were stratified by HIV status. Results: Of 339 baseline participants, 153 (45%) were women; 129 (38%) had HIV, of whom 53% were women. Overall, 105/339 participants (31%) had PRISm at baseline. HIV was associated with lower odds of PRISm (adjusted odds ratio [aOR], 0.38; 95% CI, 0.21-0.68; P = .001). Female sex trended toward increased odds of PRISm among all participants (aOR, 1.65; 95% CI, 0.99-2.75; P = .052). The association between female sex and PRISm tended to be stronger among PWH (aOR, 3.16; 95% CI, 1.14-8.76; P = .03) than among those without HIV (aOR, 1.34; 95% CI, 0.73-2.45; P = .34); this study was underpowered to detect an HIV-sex interaction of this magnitude (P = .30). Conclusions: Among Ugandan adults who recovered from pneumonia, female sex was associated with increased odds and HIV with decreased odds of PRISm, suggesting independent sex and HIV effects on PRISm pathogenesis.

12.
Nat Mater ; 23(4): 492-498, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38438620

ABSTRACT

The primordial ingredient of cuprate superconductivity is the CuO2 unit cell. Theories usually concentrate on the intra-atom Coulombic interactions dominating the 3d9 and 3d10 configurations of each copper ion. However, if Coulombic interactions also occur between electrons of the 2p6 orbitals of each planar oxygen atom, spontaneous orbital ordering may split their energy levels. This long-predicted intra-unit-cell symmetry breaking should generate an orbitally ordered phase, for which the charge transfer energy ε separating the 2p6 and 3d10 orbitals is distinct for the two oxygen atoms. Here we introduce sublattice-resolved ε(r) imaging to CuO2 studies and discover intra-unit-cell rotational symmetry breaking of ε(r). Spatially, this state is arranged in disordered Ising domains of orthogonally oriented orbital order bounded by dopant ions, and within whose domain walls low-energy electronic quadrupolar two-level systems occur. Overall, these data reveal a Q = 0 orbitally ordered state that splits the oxygen energy levels by ~50 meV, in underdoped CuO2.

13.
Poult Sci ; 103(5): 103572, 2024 May.
Article in English | MEDLINE | ID: mdl-38428355

ABSTRACT

An experiment was conducted to determine the effect of feeding reduced crude protein (CP) diets to Ross × Ross 708 male broilers while providing adequate essential amino acid (AA) concentrations on growth performance, nitrogen (N) and ammonia output, and carcass characteristics from d 1 to 33 post hatch. Birds received 1 of 6 dietary treatments (10 replicate pens per treatment) varying in CP content. Diet 1 (control) was formulated with DL-Met, L-Lys, and L-Thr (23.2, 20.7, and 19.1% CP) in the starter (1-14 d of age), grower (15-25 d of age), and finisher (26-33 d of age) periods, respectively. Dietary L-Val, Gly (only in starter period), L-Ile, L-Arg, and L-Trp were sequentially supplemented in the order of limitation in Diets 2 through 6. Dietary CP was reduced gradually across the dietary treatments resulting in a CP reduction in Diets 1 to 6 by 3.4, 3.4, and 2.3% points in the starter, grower, and finisher periods, respectively. At d 14, 25, and 33 posthatch, feed conversion decreased (P < 0.05) with L-Val addition (Diet 2) and increased (P < 0.01) with L-Val to L-Trp addition (Diet 6) to the control. Dietary treatments did not alter weights and yields of carcass, breast, drum, or thighs. Dietary CP reduction with added L-Val (Diet 2), L-Val to L-Arg (Diet 5), or L-Val to L-Trp (Diet 6) increased abdominal fat (P < 0.01) compared with control. Nitrogen excretion (g/bird; P = 0.003) and equilibrium ammonia concentration (mg/kg; P = 0.041) at day 33 reduced by 16% and 48% respectively in birds fed reduced-CP diets with L-Val to L-Trp (Diet 6) compared with control-fed birds. This study indicated that sequential addition of supplemental AA in the order of limitation from DL-Met to L-Arg allowed reduction of dietary CP beyond 2%-point without depressing growth performance and meat yield of broilers from day 1 to 33 while reducing nitrogen excretion and ammonia emissions.


Subject(s)
Amino Acids, Essential , Ammonia , Animal Feed , Animal Nutritional Physiological Phenomena , Chickens , Diet , Nitrogen , Animals , Chickens/growth & development , Chickens/physiology , Animal Feed/analysis , Male , Nitrogen/metabolism , Ammonia/metabolism , Diet/veterinary , Amino Acids, Essential/administration & dosage , Amino Acids, Essential/metabolism , Animal Nutritional Physiological Phenomena/drug effects , Diet, Protein-Restricted/veterinary , Dietary Proteins/metabolism , Dietary Proteins/administration & dosage , Random Allocation , Meat/analysis , Dietary Supplements/analysis
14.
Front Public Health ; 12: 1321173, 2024.
Article in English | MEDLINE | ID: mdl-38500722

ABSTRACT

Background: The COVID-19 pandemic has convoluted hesitancy toward vaccines, including the seasonal influenza (flu) vaccine. Because of COVID-19, the flu season has become more complicated; therefore, it is important to understand all the factors influencing the uptake of these vaccines to inform intervention targets. This article assesses factors related to the uptake of influenza and COVID-19 vaccines among adults in Tennessee. Methods: A cross-sectional, secondary data analysis of 1,400 adults was conducted in Tennessee. The adult sample came from two data sources: Data source 1 completed a baseline survey from January to March 2022, and data source 2 was completed from May to August 2022. Data on vaccine attitudes, facilitators and barriers, and communication needs were collected via random digit dial by Scientific Telephone Samples (STS). Two multivariable logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) to predict sociodemographic and overall vaccine-related factors associated with receipt or non-receipt (referent) of COVID-19 and influenza vaccines. Results: Approximately 78% of the adult sample had received the COVID-19 vaccination. A significant positive association for COVID-19 vaccine uptake was seen among those who were older (aged 50-65) (aOR = 1.9; 95% CI: 1.2-3.2), Black (aOR = 2.0; 95% CI:1.3-2.8), and had a college education and higher (aOR = 2.3; 95% CI: 1.5-3.6). However, there was a significant negative association for persons reporting they were extremely religious (aOR = 0.5; 95% CI:0.3-0.9). Over 56% of the adult sample had received the influenza vaccination this season. Those who had a higher annual household income ($80,000+) (aOR = 1.9; 95% CI: 1.3-2.6) and had health insurance (aOR = 2.6; 95% CI: 1.4-4.8) had a significant positive association with influenza vaccine receipt. However, those who were employed part-time or were unemployed had a significant negative association for influenza vaccine receipt (aOR = 0.7; 95% CI: 0.5-0.9). Both COVID-19 and influenza vaccine receipt had strongly significant positive trends with increasing belief in effectiveness and trust (p < 0.0001) and strongly significant negative trends with higher levels of overall vaccine hesitancy (p < 0.0001). Conclusion: Strategies to increase COVID-19 and influenza vaccination should be age-specific, focus on increasing geographical and financial access, and offer tailored messages to address concerns about these vaccines.


Subject(s)
COVID-19 , Influenza Vaccines , Influenza, Human , Adult , Humans , Influenza, Human/epidemiology , Influenza, Human/prevention & control , COVID-19 Vaccines , Seasons , Tennessee/epidemiology , Cross-Sectional Studies , Pandemics , Vaccination Coverage , COVID-19/epidemiology , COVID-19/prevention & control , Health Knowledge, Attitudes, Practice , Vaccination
15.
Res Sq ; 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38410451

ABSTRACT

Introduction: Universal TB education and counseling (TEC) is routinely recommended for promoting knowledge and medication adherence, but the quality of delivery often varies because of inadequate clinic space, time, and health worker training. Peer-led counseling is a promising but understudied solution to these challenges. We sought to evaluate the efficacy of a peer-led TEC strategy among newly diagnosed adults initiating TB treatment in Kampala, Uganda. Methods: We conducted a longitudinal, pre-post implementation study comparing the routine, healthcare-worker-led and peer-led strategies for delivery of TEC to consecutive adult persons with TB at a large, public primary-care clinic. Trained staff administered a standardized TB knowledge survey to all persons with TB immediately following TEC. We compared TB knowledge by type of TEC received using t-tests. Results: We enrolled 161 persons with TB, 80 who received conventional TEC from health workers between June and July 2018, and 81 who received peer-led TEC between August and November 2019. The proportions of women (28% vs. 31%, p = 0.64) and persons living with HIV (36% vs 30%, p = 0.37) were similar in the pre- and post-implementation periods. Peer-led TEC was associated with a more significant increase in disease-specific (difference +21%, 95% CI +18% to + 24%, p < 0.0001) and treatment-specific TB knowledge scores (difference +14%, 95% CI + 10% to + 18%, p< 0.0001) than routine healthcare worker-delivered TEC. All TB knowledge constructs were significantly higher for those in the post-implementation period than those in the pre-implementation period. Nine participants met our threshold for adequate knowledge (score ≥ 90%) for disease-specific TB knowledge in the pre-implementation period compared to 63 (78%) in the post-implementation period (+67%, 95% CI + 55% - +78%, p < 0.001). Twenty-eight (35%) met the adequate knowledge threshold for TB treatment-specific knowledge in the pre-implementation period compared to 60 (74%) in the post-implementation period (+ 39%, 95% CI + 25 to + 53%, p < 0.0001). Finally, the proportion achieving TB treatment success (cure or completed) increased substantially from the pre-implementation period (n = 49, 68%) to the post-implementation period (n = 63, 88%), a difference of + 19% (95% CI + 6% to + 33%, p = 0.005). Conclusion: Our findings suggest that peer-led TEC is more efficacious than routine TEC at improving TB knowledge and treatment outcomes. Future studies should evaluate the implementation and effectiveness of the peer-led TEC strategy when scaled to a larger number of clinics.

16.
Genome Biol ; 25(1): 56, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38409056

ABSTRACT

BACKGROUND: The development of single-cell RNA sequencing (scRNA-seq) has enabled scientists to catalog and probe the transcriptional heterogeneity of individual cells in unprecedented detail. A common step in the analysis of scRNA-seq data is the selection of so-called marker genes, most commonly to enable annotation of the biological cell types present in the sample. In this paper, we benchmark 59 computational methods for selecting marker genes in scRNA-seq data. RESULTS: We compare the performance of the methods using 14 real scRNA-seq datasets and over 170 additional simulated datasets. Methods are compared on their ability to recover simulated and expert-annotated marker genes, the predictive performance and characteristics of the gene sets they select, their memory usage and speed, and their implementation quality. In addition, various case studies are used to scrutinize the most commonly used methods, highlighting issues and inconsistencies. CONCLUSIONS: Overall, we present a comprehensive evaluation of methods for selecting marker genes in scRNA-seq data. Our results highlight the efficacy of simple methods, especially the Wilcoxon rank-sum test, Student's t-test, and logistic regression.


Subject(s)
Benchmarking , Single-Cell Analysis , Single-Cell Analysis/methods , Exome Sequencing , Sequence Analysis, RNA , Gene Expression Profiling , Software
17.
mSphere ; 9(1): e0050423, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38073033

ABSTRACT

Cryptococcus is a ubiquitous environmental fungus and frequent colonizer of human lungs. Colonization can lead to diverse outcomes, from clearance to long-term colonization to life-threatening meningoencephalitis. Regardless of the outcome, the process starts with an encounter with phagocytes. Using the zebrafish model of this infection, we have noted that cryptococcal cells first spend time inside macrophages before they become capable of pathogenic replication and dissemination. What "licensing" process takes place during this initial encounter, and how are licensed cryptococcal cells different? To address this, we isolated cryptococcal cells after phagocytosis by cultured macrophages and found these macrophage-experienced cells to be markedly more virulent in both zebrafish and mouse models. Despite producing a thick polysaccharide capsule, they were still subject to phagocytosis by macrophages in the zebrafish. Analysis of antigenic cell wall components in these licensed cells demonstrated that components of mannose and chitin are more available for staining than they are in culture-grown cells or cells with capsule production induced in vitro. Cryptococcus is capable of exiting or transferring between macrophages in vitro, raising the likelihood that this fungus alternates between intracellular and extracellular life during growth in the lungs. Our results raise the possibility that intracellular life has its advantages over time, and phagocytosis-induced alteration in mannose and chitin exposure is one way that makes subsequent rounds of phagocytosis more beneficial to the fungus.IMPORTANCECryptococcosis begins in the lungs and can ultimately travel through the bloodstream to cause devastating infection in the central nervous system. In the zebrafish model, small amounts of cryptococcus inoculated into the bloodstream are initially phagocytosed and become far more capable of dissemination after they exit macrophages. Similarly, survival in the mouse lung produces cryptococcal cell types with enhanced dissemination. In this study, we have evaluated how phagocytosis changes the properties of Cryptococcus during pathogenesis. Macrophage-experienced cells (MECs) become "licensed" for enhanced virulence. They out-disseminate culture-grown cells in the fish and out-compete non-MECs in the mouse lung. Analysis of their cell surface demonstrates that MECs have increased availability of cell wall components mannose and chitin substances involved in provoking phagocytosis. These findings suggest how Cryptococcus might tune its cell surface to induce but survive repeated phagocytosis during early pathogenesis in the lung.


Subject(s)
Cryptococcosis , Cryptococcus neoformans , Animals , Mice , Humans , Zebrafish/microbiology , Cryptococcosis/microbiology , Virulence , Mannose , Macrophages/microbiology , Chitin/metabolism
18.
J Am Coll Radiol ; 21(1): 70-80, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37863151

ABSTRACT

OBJECTIVES: To decrease call burden on pediatric neuroradiologists, we developed guidelines for appropriate use of MR overnight. These guidelines were implemented using triage by in-house generalist pediatric radiologists. Process measures and balancing measures were assessed during implementation. METHODS: For this improvement project, interdepartmental consensus guidelines were developed using exploratory mixed-methods design. Implementation of triage used plan-do-study-act cycles. Process measures included reduction in the number of telephone calls, frequency of calls, triage decisions, and number and type of examinations ordered. Balancing measures included burden of time and effort to the generalist radiologists. Differences in examination orders between implementation intervals was assessed using Kruskal-Wallis, with significance at P < .05. RESULTS: Consensus defined MR requests as "do," "defer," or "divert" (to CT). Guidelines decreased neuroradiologist calls 74% while adding minimal burden to the generalist radiologists. Most nights had zero or one triage request and the most common triage decision was "do," and the most common examination was routine brain MR. Number of MR ordered and completed overnight did not significantly change with triage. DISCUSSION: Multidisciplinary consensus for use of pediatric neurological MR during limited resource hours overnight is an example of imaging stewardship that decreased the burden of calls and burnout for neuroradiologists while maintaining a comparable level of service to the ordering clinicians.


Subject(s)
Telephone , Triage , Humans , Child , Time Factors
19.
Respir Res ; 24(1): 311, 2023 Dec 13.
Article in English | MEDLINE | ID: mdl-38093373

ABSTRACT

QUESTION: Severe asthma and COPD exacerbations requiring hospitalization are linked to increased disease morbidity and healthcare costs. We sought to identify Electronic Health Record (EHR) features of severe asthma and COPD exacerbations and evaluate the performance of four machine learning (ML) and one deep learning (DL) model in predicting readmissions using EHR data. STUDY DESIGN AND METHODS: Observational study between September 30, 2012, and December 31, 2017, of patients hospitalized with asthma and COPD exacerbations. RESULTS: This study included 5,794 patients, 1,893 with asthma and 3,901 with COPD. Patients with asthma were predominantly female (n = 1288 [68%]), 35% were Black (n = 669), and 25% (n = 479) were Hispanic. Black (44 vs. 33%, p = 0.01) and Hispanic patients (30 vs. 24%, p = 0.02) were more likely to be readmitted for asthma. Similarly, patients with COPD readmissions included a large percentage of Blacks (18 vs. 10%, p < 0.01) and Hispanics (8 vs. 5%, p < 0.01). To identify patients at high risk of readmission index hospitalization data of a subset of 2,682 patients, 777 with asthma and 1,905 with COPD, was analyzed with four ML models, and one DL model. We found that multilayer perceptron, the DL method, had the best sensitivity and specificity compared to the four ML methods implemented in the same dataset. INTERPRETATION: Multilayer perceptron, a deep learning method, had the best performance in predicting asthma and COPD readmissions, demonstrating that EHR and deep learning integration can improve high-risk patient detection.


Subject(s)
Asthma , Deep Learning , Pulmonary Disease, Chronic Obstructive , Humans , Female , Male , Patient Readmission , Retrospective Studies , Asthma/diagnosis , Asthma/epidemiology , Asthma/therapy , Hospitalization , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/therapy
20.
PLOS Glob Public Health ; 3(12): e0001813, 2023.
Article in English | MEDLINE | ID: mdl-38051699

ABSTRACT

We conducted a pilot randomized controlled trial among patients initiating treatment for drug-sensitive tuberculosis (TB). Participants received real-time electronic adherence monitors and were randomized (1:1:1) to: (i) daily SMS (reminders to TB patients and notifications to social supporters sent daily for 3 months, then triggered by late or missed dosing for 3 months); (ii) weekly SMS (reminders to TB patients and notifications to social supporters sent weekly for 3 months, then triggered by late or missed dosing for 3 months); or (iii) control (no SMS). Feasibility was mainly verified by the technical function of the intervention at Month 6. The primary outcome was percent adherence as ascertained by the real time monitor. Quantitative feasibility/acceptability data were summarized descriptively. Percentage adherence and adherence patterns were assessed and compared by linear regression models. Qualitative acceptability data was collected through interviews and analyzed using content analysis. Among 63 participants, the median age was 35 years, 75% had no regular income, and 84% were living with HIV. Feasibility was demonstrated as most of the daily [1913/2395 (80%)] and weekly [631/872 (72%)] SMS reminders to TB patients were sent successfully. Also, most of the daily [1577/2395 (66%)] and weekly [740/872 (85%)] SMS notifications to social supporters and adherence data (96%) were sent successfully. Challenges included TB status disclosure, and financial constraints. All patients perceived the intervention to be useful in reminding and motivating them to take medication. Median adherence (IQR) in the daily SMS, weekly SMS, and control arms was 96.1% (84.8, 98.0), 92.5% (80.6, 96.3), and 92.2% (56.3, 97.8), respectively; however, differences between the intervention and control arms were not statistically significant. Real-time monitoring linked to SMS was feasible and acceptable and may have improved TB medication adherence. Larger studies are needed to further assess impact on adherence and clinical outcomes. Trial registration. ClinicalTrials.gov registration number: NCT03800888. https://ichgcp.net/clinical-trials-registry/NCT03800888.

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