Modeling the effectiveness of One Health interventions against the zoonotic hookworm Ancylostoma ceylanicum

Hookworm disease is a major global public health concern, annually affecting 500-700 million of the world's poorest people. The World Health Organization is targeting the elimination of hookworm as a public health problem by 2030 using a strategy of mass drug administration (MDA) to at-risk human populations. However, in Southeast Asia and the Pacific the zoonotic hookworm species, Ancylostoma ceylanicum, is endemic in dogs and commonly infects people. This presents a potential impediment to the effectiveness of MDA that targets only humans. Here, we develop a novel multi-host (dog and human) transmission model of A. ceylanicum and compare the effectiveness of human-only and "One Health" (human plus dog) MDA strategies under a range of eco-epidemiological assumptions. We show that One Health interventions-targeting both dogs and humans-could suppress prevalence in humans to ≤ 1% by the end of 2030, even with only modest coverage (25-50%) of the animal reservoir. With increasing coverage, One Health interventions may even interrupt transmission. We discuss key unresolved questions on the eco-epidemiology of A. ceylanicum, the challenges of delivering MDA to animal reservoirs, and the growing importance of One Health interventions to human public health

Osteogenesis Imperfecta – Experience of Dona Estefânia’s Hospital Orthopedics’ Department

Introdução/Objectivos: A osteogénese imperfeita (OI) é uma doença genética caracterizada por fragilidade óssea e osteopenia. O tratamento implica uma abordagem multidisciplinar e tem como objectivo a melhoria da qualidade de vida. Os autores pretendem descrever as características de uma amostra de crianças com OI, avaliar o tratamento realizado e a evolução clínica pré e pós terapêutica. Material e Métodos: Estudo observacional, longitudinal, retrospectivo e analítico, com base nos dados obtidos da consulta dos processos de todos os doentes com OI incluídos no protocolo de tratamento com pamidronato no Hospital Dona Estefânia. As variáveis estudadas foram: sexo, idade de diagnóstico, antecedentes familiares de OI, idade de fractura, localização da fractura, número de fracturas, terapêutica médica/cirúrgica, idade de início do tratamento médico, número de ciclos de terapêutica médica, idade da terapêutica cirúrgica, complicações da terapêutica cirúrgica. Adoptou-se um nível de significância de 5%. Resultados: De 21 doentes, 61,9% eram do sexo masculino e 11 tinham registado o diagnóstico do tipo de OI (cinco do tipo I, três tipo III, três tipo IV). A idade média de diagnóstico foi de 20,6 meses, verificando-se dois picos diagnósticos: no primeiro mês – 37%, e aos 24 meses - 26%. Em média os doentes apresentaram 0,62 fracturas/doente/ano, 17,4% das quais no período perinatal e 62% antes dos três anos de idade. A maioria das fracturas ocorreu nos membros inferiores (55,6%). Todos os doentes realizaram tratamento médico, com início em média aos 4,3 anos. Na amostra com seguimento (n=14) verificou-se diminuição no número de fracturas após o início do tratamento com pamidronato (de 0,76 para 0,35 fracturas/doente/ano). Foram colocadas cavilhas endomedulares em nove doentes (64,3%). Em oito doentes foram colocadas nos fémures, quatro unilaterais e quatro bilaterais, não existindo antecedentes de fractura em três casos. Não se registaram novas fracturas nos ossos encavilhados. Conclusão: A OI é uma doença com uma ampla variabilidade clínica que depende maioritariamente do seu tipo. Apesar de não existir tratamento curativo, o tratamento médico com bifosfonatos e o tratamento cirúrgico, com colocação de cavilhas endomedulares, parece reduzir a incidência de novas fracturas

An early warning risk prediction tool (RECAP-V1) for patients diagnosed with COVID-19: the protocol for a statistical analysis plan

Background: Since the start of the Covid-19 pandemic efforts have been made to develop early warning risk scores to help clinicians decide which patient is likely to deteriorate and require hospitalisation. The RECAP (Remote COVID Assessment in Primary Care) study investigates the predictive risk of hospitalisation, deterioration, and death of patients with confirmed COVID-19, based on a set of parameters chosen through a Delphi process done by clinicians. The study aims to use rich data collected remotely through the use of electronic data templates integrated in the electronic health systems of a number of general practices across the UK to construct accurate predictive models that will use pre-existing conditions and monitoring data of a patient’s clinical parameters such as blood oxygen saturation to make reliable predictions as to the patient’s risk of hospital admission, deterioration, and death. Objective: We outline the statistical methods to build the prediction model to be used in the prioritisation of patients in the primary care setting. The statistical analysis plan for the RECAP study includes as primary outcome the development and validation of the RECAP-V1 prediction model. Such prediction model will be adapted as a three-category risk score split into red (high risk), amber (medium risk), and green (low risk) for any patient with suspected covid-19. The model will predict risk of deterioration, hospitalisation, and death. Methods: After the data has been collected, we will assess the degree of missingness and use a combination of traditional data imputation using multiple imputation by chained equations, as well as more novel machine learning approaches to impute the missing data for the final analysis. For predictive model development we will use multiple logistic regressions to construct the model on a training dataset, as well as validating the model on an independent dataset. The model will also be applied for multiple different datasets to assess both its performance in different patient groups, and applicability for different methods of data collection. Results: As of 5th of May 2021 we have recruited 2280 patients for the main dataset for model development, as well as a further 1741 patients for the validation dataset. Final analysis will commence as soon as data for 2880 are collected. Conclusions: We believe that the methodology for the development of the RECAP V1 prediction model as well as the risk score will provide clinicians with a statistically robust tool to help prioritise Covid-19 patients. Clinical Trial: Trial registration number: NCT0443504

Profiling the circulating miRnome reveals a temporal regulation of the bone injury response

Bone injury healing is an orchestrated process that starts with an inflammatory phase followed by repair and remodelling of the bone defect. The initial inflammation is characterized by local changes in immune cell populations and molecular mediators, including microRNAs (miRNAs). However, the systemic response to bone injury remains largely uncharacterized. Thus, this study aimed to profile the changes in the plasma miRnome after bone injury and determine its biological implications. Methods: A rat model of femoral bone defect was used, and animals were evaluated at days 3 and 14 after injury. Non-operated (NO) and sham operated animals were used as controls. Blood and spleen were collected and peripheral blood mononuclear cells (PBMC) and plasma were separated. Plasma miRnome was determined by RT-qPCR array and bioinformatics Ingenuity pathway analysis (IPA) was performed. Proliferation of bone marrow mesenchymal stem/stromal cells (MSC) was evaluated by Ki67 staining and high-throughput cell imaging. Candidate miRNAs were evaluated in splenocytes by RT-qPCR, and proteins found in the IPA analysis were analysed in splenocytes and PBMC by Western blot. Results: Bone injury resulted in timely controlled changes to the miRNA expression profile in plasma. At day 3 there was a major down-regulation of miRNA levels, which was partially recovered by day 14 post-injury. Interestingly, bone injury led to a significant up-regulation of let-7a, let-7d and miR-21 in plasma and splenocytes at day 14 relative to day 3 after bone injury, but not in sham operated animals. IPA predicted that most miRNAs temporally affected were involved in cellular development, proliferation and movement. MSC proliferation was analysed and found significantly increased in response to plasma of animals days 3 and 14 post-injury, but not from NO animals. Moreover, IPA predicted that miRNA processing proteins Ago2 and Dicer were specifically inhibited at day 3 post-injury, with Ago2 becoming activated at day 14. Protein levels of Ago2 and Dicer in splenocytes were increased at day 14 relative to day 3 post-bone injury and NO animals, while in PBMC, levels were reduced at day 3 (albeit Dicer was not significant) and remained low at day 14. Ephrin receptor B6 followed the same tendency as Ago2 and Dicer, while Smad2/3 was significantly decreased in splenocytes from day 14 relative to NO and day 3 post-bone injury animals. Conclusion: Results show a systemic miRNA response to bone injury that is regulated in time and is related to inflammation resolution and the start of bone repair/regeneration, unravelling candidate miRNAs to be used as biomarkers in the monitoring of healthy bone healing and as therapeutic targets for the development of improved bone regeneration therapies.This work was funded by project NORTE-01-0145-FEDER-000012, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and AO Foundation-Switzerland (project S-15-83S). AMS, MIA, CC and JHT were supported by FCT-Fundação para a Ciência e a Tecnologia, through fellowships SFRH/BD/ 85968/2012, SFRH/BPD/91011/2012, SFRH/BDP/ 87071/2012 and SFRH/BD/112832/2015, respecttively. Work in Dr. Calin's laboratory is supported by National Institutes of Health (NIH/NCATS) grant UH3TR00943-01 through the NIH Common Fund, Office of Strategic Coordination (OSC), the NIH/NCI grant 1R01CA182905-01, a U54 grant-UPR/MDACC Partnership for Excellence in Cancer Research 2016 Pilot Project, a Team DOD (CA160445P1) grant, a Ladies Leukemia League grant, a CLL Moonshot Flagship project, a SINF 2017 grant, and the Estate of C. G. Johnson, J

Correction to: Atypical pathogens in hospitalized patients with community-acquired pneumonia: a worldwide perspective.

An amendment to this paper has been published and can be accessed via the original article

Over 500 Days in the Life of the Photosphere of the Type Iax Supernova SN 2014dt

Type Iax supernovae (SNe Iax) are the largest known class of peculiar white dwarf SNe, distinct from normal Type Ia supernovae (SNe Ia). The unique properties of SNe Iax, especially their strong photospheric lines out to extremely late times, allow us to model their optical spectra and derive the physical parameters of the long-lasting photosphere. We present an extensive spectral timeseries, including 21 new spectra, of SN Iax 2014dt from +11 to +562 days after maximum light. We are able to reproduce the entire timeseries with a self-consistent, nearly unaltered deflagration explosion model from Fink et al. using TARDIS, an open source radiative-transfer code. We find that the photospheric velocity of SN 2014dt slows its evolution between +64 and +148 days, which closely overlaps the phase when we see SN 2014dt diverge from the normal spectral evolution of SNe Ia (+90 to +150 days). The photospheric velocity at these epochs, ~400-1000 km s-1, may demarcate a boundary within the ejecta below which the physics of SNe Iax and normal SNe Ia differ. Our results suggest that SN 2014dt is consistent with a weak deflagration explosion model that leaves behind a bound remnant and drives an optically thick, quasi-steady-state wind creating the photospheric lines at late times. The data also suggest that this wind may weaken at epochs past +450 days, perhaps indicating a radioactive power source that has decayed away

Ultraviolet Spectroscopy and TARDIS Models of the Broad-lined Type-Ic Supernova 2014ad

Few published ultraviolet (UV) spectra exist for stripped-envelope supernovae, and none to date for broad-lined Type Ic supernovae (SN Ic-bl). These objects have extremely high ejecta velocities and are the only supernova type directly linked to gamma-ray bursts (GRBs). Here we present two epochs of HST/STIS spectra of the SN Ic-bl 2014ad, the first UV spectra for this class. We supplement this with 26 new epochs of ground-based optical spectra, augmenting a rich spectral time series. The UV spectra do not show strong features, likely due to high opacity, and are consistent with broadened versions of other SN Ic spectra observed in the UV. We measure Fe II 5169 Angstrom velocities and show that SN 2014ad has even higher ejecta velocities than most SNe Ic both with and without observed GRBs. We construct models of the SN 2014ad UV+optical spectra using TARDIS, a 1D Monte-Carlo radiative-transfer spectral synthesis code. The models fit the data well at multiple epochs in the optical but underestimate the flux in the UV. We find that high densities at high velocities are needed to reproduce the spectra, with $\sim$3 M$_\odot$ of material at $v >$ 22,000 km s$^{-1}$, assuming spherical symmetry. Our nebular line fits suggest a steep density profile at low velocities. Together, these results imply a higher total ejecta mass than estimated from previous light curve analysis and expected from theory. This may be reconciled by a flattening of the density profile at low velocity and extra emission near the center of the ejecta.Comment: 25 pages, 14 figures, submitted to AAS Journal

Cell walls of the dimorphic fungal pathogens Sporothrix schenckii and Sporothrix brasiliensis exhibit bilaminate structures and sloughing of extensive and intact layers

This work was supported by the Fundação Carlos Chagas de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), grants E-26/202.974/2015 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grants 229755/2013-5, Brazil. LMLB is a senior research fellow of CNPq and Faperj. NG acknowledged support from the Wellcome Trust (Trust (097377, 101873, 200208) and MRC Centre for Medical Mycology (MR/N006364/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Over 500 Days in the Life of the Photosphere of the Type Iax Supernova SN 2014dt

Type Iax supernovae (SN Iax) are the largest known class of peculiar white dwarf supernovae, distinct from normal Type Ia supernovae (SN Ia). The unique properties of SN Iax, especially their strong photospheric lines out to extremely late times, allow us to model their optical spectra and derive physical parameters for the long-lasting photosphere. We present an extensive spectral timeseries, including 21 new spectra, of SN Iax 2014dt from +11 to +562 days after maximum light. We are able to reproduce the entire timeseries with a self-consistent, nearly unaltered deflagration explosion model from Fink et al. (2014) using TARDIS, an open-source radiative transfer code (Kerzendorf & Sim 2014; Kerzendorf et al. 2023). We find that the photospheric velocity of SN 2014dt slows its evolution between +64 and +148 days, which closely overlaps the phase when we see SN 2014dt diverge from the normal spectral evolution of SN Ia (+90 to +150 days). The photospheric velocity at these epochs, ~400$-$1000 km s$^{-1}$, may demarcate a boundary within the ejecta below which the physics of SN Iax and normal SN Ia differ. Our results suggest that SN 2014dt is consistent with a weak deflagration explosion model that leaves behind a bound remnant and drives an optically thick, quasi-steady-state wind creating the photospheric lines at late times. The data also suggest that this wind may weaken at epochs past +450 days, perhaps indicating a radioactive power source that has decayed away.Comment: Accepted to ApJ, 22 pages, 8 figures, 3 table