Re-evaluation of phytohormone-independent division of tobacco protoplast-derived cells

We have used a [3H] thymidine incorporation assay and microscopic observation in order to reassess recently published data dealing with the response of tobacco protoplasts to phytohormones, lipochitooligosaccharides and peptides (Harling et al., 1997; Hayashi et al., 1992; Miklashevichs et al., 1996; Miklashevichs et al., 1997; Rohrig et al., 1995; Rohrig et al., 1996; van de Sande et al., 1996; Walden et al., 1994). These proliferation assays reveal that, in contrast to published data, isolated cells of the investigated mutant plant lines axi159 (Hayashi et al., 1992; Walden et al., 1994), axi4/1 (Harling et al., 1997) and cyil (Miklashevichs et al., 1997), which were generated by activation T-DNA tagging, were unable to grow in the absence of auxin or cytokinin. Furthermore, lipochitooligosaccharides which play a key role in the induction of nodules on roots of legumes were unable to promote auxin- or cytokinin-independent cell division in tobacco protoplasts as claimed by Rohrig et al. (1995, 1996). The finding of van de Sande et al. (1996) that ENOD40 confers tolerance of high auxin concentration to wild-type tobacco protoplasts was also reinvestigated. The results of our investigations show that we were unable to reproduce the proliferation data presented in this study, which were obtained by counting tobacco protoplast-derived cells undergoing division. In total, none of the published data on phytohormone-independent division of tobacco cells could be reproduced.Peer reviewe

Cost Effectiveness of Strategies for Caring for Critically Ill Patients with COVID-19 in Tanzania.

BACKGROUND: The resources for critical care are limited in many settings, exacerbating the significant morbidity and mortality associated with critical illness. Budget constraints can lead to choices between investing in advanced critical care (e.g. mechanical ventilators in intensive care units) or more basic critical care such as Essential Emergency and Critical Care (EECC; e.g. vital signs monitoring, oxygen therapy, and intravenous fluids). METHODS: We investigated the cost effectiveness of providing EECC and advanced critical care in Tanzania in comparison with providing 'no critical care' or 'district hospital-level critical care' using coronavirus disease 2019 (COVID-19) as a tracer condition. We developed an open-source Markov model ( https://github.com/EECCnetwork/POETIC_CEA ) to estimate costs and disability-adjusted life-years (DALYs) averted, using a provider perspective, a 28-day time horizon, patient outcomes obtained from an elicitation method involving a seven-member expert group, a normative costing study, and published literature. We performed a univariate and probabilistic sensitivity analysis to assess the robustness of our results. , RESULTS: EECC is cost effective 94% and 99% of the time when compared with no critical care (incremental cost-effectiveness ratio [ICER] $37 [-$9 to $790] per DALY averted) and district hospital-level critical care (ICER$14 [-$200 to$263] per DALY averted), respectively, relative to the lowest identified estimate of the willingness-to-pay threshold for Tanzania ($101 per DALY averted). Advanced critical care is cost effective 27% and 40% of the time, when compared with the no critical care or district hospital-level critical care scenarios, respectively. CONCLUSION: For settings where there is limited or no critical care delivery, implementation of EECC could be a highly cost-effective investment. It could reduce mortality and morbidity for critically ill COVID-19 patients, and its cost effectiveness falls within the range considered 'highly cost effective'. Further research is needed to explore the potential of EECC to generate even greater benefits and value for money when patients with diagnoses other than COVID-19 are accounted for

RARE-Bestpractices: a platform for sharing best practices for the management of rare diseases

No abstract available

RARE-Bestpractices: a platform for sharing best practices for the management of rare diseases

No abstract available

How Does the VSG Coat of Bloodstream Form African Trypanosomes Interact with External Proteins?

Variations on the statement "the variant surface glycoprotein (VSG) coat that covers the external face of the mammalian bloodstream form of Trypanosoma brucei acts a physical barrier" appear regularly in research articles and reviews. The concept of the impenetrable VSG coat is an attractive one, as it provides a clear model for understanding how a trypanosome population persists; each successive VSG protects the plasma membrane and is immunologically distinct from previous VSGs. What is the evidence that the VSG coat is an impenetrable barrier, and how do antibodies and other extracellular proteins interact with it? In this review, the nature of the extracellular surface of the bloodstream form trypanosome is described, and past experiments that investigated binding of antibodies and lectins to trypanosomes are analysed using knowledge of VSG sequence and structure that was unavailable when the experiments were performed. Epitopes for some VSG monoclonal antibodies are mapped as far as possible from previous experimental data, onto models of VSG structures. The binding of lectins to some, but not to other, VSGs is revisited with more recent knowledge of the location and nature of N-linked oligosaccharides. The conclusions are: (i) Much of the variation observed in earlier experiments can be explained by the identity of the individual VSGs. (ii) Much of an individual VSG is accessible to antibodies, and the barrier that prevents access to the cell surface is probably at the base of the VSG N-terminal domain, approximately 5 nm from the plasma membrane. This second conclusion highlights a gap in our understanding of how the VSG coat works, as several plasma membrane proteins with large extracellular domains are very unlikely to be hidden from host antibodies by VSG.The authors’ lab is funded by the Wellcome Trust (093008/Z10/Z) and the Medical Research Council (MR/L008246/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version of the article. It was first available from PLOS via http://dx.doi.org/10.1371/journal.ppat.100525

Post-COVID-19 Impairment of the Senses of Smell, Taste, Hearing, and Balance

Background: Various symptoms have been associated with COVID-19, but little is known about the impacts of COVID-19 on the sensory system, risk factors, and the duration of symptoms. This study assesses olfactory, gustatory, hearing, and vestibular systems after COVID-19. Methods: This cross-sectional, single-center study involved 50 patients one to six months after COVID-19 and reports their patient records and the extent, onset, and duration of olfactory, gustatory, hearing, and balance disorders using questionnaires during and after COVID-19. Sensory symptoms were objectively studied using the following clinical tests after COVID-19 Sniffin’ Sticks, taste tests, tone/speech audiometry, and video head impulse test. Results: Post-COVID-19-patients were suffering from olfactory and gustatory impairment for up to six months. According to the Dizziness Handicap Inventory, balance disorders were less noticed: Overall, about 40% of the patients during COVID-19 and nearly all patients recovered within six months. After COVID-19, clinical tests revealed that 75% were suffering from hyposomnia/anosmia, and 20% of all patients reported mild hypogeusia for up to six months. Vestibular disorders and hearing impairment rarely/did not occur. Females were significantly more affected by sensory impairments than males. Conclusions: COVID-19 particularly caused olfactory and gustatory impairment; balance disorders were present too; vestibular and auditory symptoms were negligible

Neural classification maps for distinct word combinations in Broca’s area

Humans are equipped with the remarkable ability to comprehend an infinite number of utterances. Relations between grammatical categories restrict the way words combine into phrases and sentences. How the brain recognises different word combinations remains largely unknown, although this is a necessary condition for combinatorial unboundedness. Here, we used functional magnetic resonance imaging and multivariate pattern analysis to explore whether distinct neural populations of a known language network hub —Broca’s area—are specialised for recognising distinct simple word combinations. The phrases consisted of a noun (flag) occurring either with a content word, an adjective (green flag), or with a function word, a determiner (that flag). The key result is that the distribution of neural populations classifying word combination in Broca’s area seems sensitive to neuroanatomical subdivisions within this area, irrespective of task. The information patterns for adjective + noun were localised in the anterior part (BA45) whereas those for determiner + noun were localised in the posterior part (BA44). Our findings provide preliminary answers to the fundamental question of how lexico-grammatical access and word combination interact during simple word combination, with the observation that Broca’s area is sensitive to the recognition of categorical relationships during combinatory processing, based on different demands placed on syntactic and semantic processing. This supports the hypothesis that the combinatorial power of language consists of some neural computation capturing phrasal differences when processing linguistic input

Assessing long-term, vestibulotoxic side effects after gentamicin therapy in neonatal sepsis or infection using video head impulse test

Study backgroundNewborn infection and sepsis remain serious problems. Guideline-compliant therapy includes, among other therapeutics, calculated intravenous antibiosis with gentamicin. One of the known side effects of gentamicin is severe vestibulotoxicity, which can be detected using the video head impulse test (VHIT), which is a sensitive examination method for the detection of vestibular hypofunction in children and adults. Previous studies on the vestibulotoxicity of gentamicin in newborns were carried out using caloric testing, rotary testing, and electronystagmography. Nevertheless, there are currently no data available on VHIT examinations in children who have been treated with neonatal gentamicin therapy.MethodsA single-center, prospective cross-sectional study, was conducted at a tertial referral center. VHIT was performed on 23 children aged 3–7 years who had received intravenous gentamicin therapy for at least five days as part of the treatment of newborn sepsis between 2012 and 2016. Main outcome was median gain and occurrence of refixational saccades as measured with VHIT. In addition, the children's parents received questionnaires to detect possible risk factors and vestibular and cochlear abnormalities.ResultsOut of 23 children with a mean age of four years and seven months (ranging from 3 to 7 years), 11 (47.8%) indicated abnormal results in VHIT. The VHIT results were unilaterally abnormal in six children (26.1%) and bilaterally abnormal in five others (21.7%). Additionally, five of the children with an abnormal HIT had abnormalities, as found in the questionnaire results.Conclusionand Relevance: Almost half of the children observed after having undergone gentamicin therapy as newborns showed abnormalities in VHIT, although they did not show any clinical signs of disbalance or vestibular hypofunction. VHIT can serve as a sensitive investigation method for the early screening of post-therapeutic vestibulotoxic side effects after gentamicin therapy in children. Additionally, VHIT can enable early intervention in these children

A literature review on the implementation of Peer Instruction interactive teaching method (1991 to 2015)

Este trabalho apresenta resultados de uma revisão da literatura acerca da implementação da metodologia interativa de ensino Peer Instruction (PI). Respondemos às seguintes questões de pesquisa: Em quais contextos de ensino (nível de ensino, país, área de ensino e disciplinas) pesquisadores têm investigado o PI? Que impactos o PI tem produzido na aprendizagem dos estudantes? Quais são os resultados instrucionais da implementação do PI em termos das atitudes dos professores em relação à metodologia e das modificações feitas na estrutura original da metodologia? Quais os principais aspectos teóricos e metodológicos que pesquisadores utilizam para investigar implementações do PI? Os resultados da literatura apontam que grande parte das publicações foram conduzidas em universidades norte americanas, em disciplinas da área STEM, com destaque à disciplina de Física. A adoção do PI apresneta impactos positivos na aprendizagem conceitual dos estudantes, na habilidade de resolução de problemas e no denesmpenho acadêmico. Desenvolve sentimentos positivosrelacionados à aprendizagem dos conteúdos e à metodologia. Professores realizam modificações ao implementar o PI integrando-o com outras metodologias, demonstrando sua flexibilidade; A maioria dos estudos é apoiada por análçises empíricas e estatísticas, mas não por estruturas conceituais ou referenciais teóricos. Esta lacuna apresenta oportunidades para constribuições futuras.This paper presents a review of literature on the implementation of the interactive student-centered teaching method Peer Instruction (PI). We answer the following research questions: In wich teaching contexts (education level, country, teaching area and disciplines) habe researchers investigated PI? What student outcomes are detailed in PI implementation studies? What are the instructional outcomes of PI adoption among instructors, in terms of teacher attitudes towards the methodology and modifications made to the original structure of the methodology? What are the theoretical and methodolojical approaches researchers use to study PI implementation? The results of the literature demonstrate that the large fields, particulary within the discipline of Physics. PI implementation shows increases in the conceptual learning teaching methods, demonstratin the methodology's flexible nature. Most studies on PI implementation are supported by empirical and statistical analysis but are not guided by formal conceptual or theoretical frameworks. This gap presents opportunities for future contribuitions