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1.
Science ; 375(6577): 167-172, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35025654

RESUMO

Filament assembly of amyloid-ß peptides ending at residue 42 (Aß42) is a central event in Alzheimer's disease. Here, we report the cryo­electron microscopy (cryo-EM) structures of Aß42 filaments from human brains. Two structurally related S-shaped protofilament folds give rise to two types of filaments. Type I filaments were found mostly in the brains of individuals with sporadic Alzheimer's disease, and type II filaments were found in individuals with familial Alzheimer's disease and other conditions. The structures of Aß42 filaments from the brain differ from those of filaments assembled in vitro. By contrast, in AppNL-F knock-in mice, Aß42 deposits were made of type II filaments. Knowledge of Aß42 filament structures from human brains may lead to the development of inhibitors of assembly and improved imaging agents.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/ultraestrutura , Química Encefálica , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/ultraestrutura , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Peptídeos beta-Amiloides/genética , Animais , Microscopia Crioeletrônica , Feminino , Técnicas de Introdução de Genes , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Modelos Animais , Modelos Moleculares , Fragmentos de Peptídeos/genética , Conformação Proteica , Conformação Proteica em Folha beta , Domínios Proteicos , Dobramento de Proteína
2.
Acta Neuropathol Commun ; 9(1): 189, 2021 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-34819144

RESUMO

Peripheral administration (oral, intranasal, intraperitoneal, intravenous) of assembled A53T α-synuclein induced synucleinopathy in heterozygous mice transgenic for human mutant A53T α-synuclein (line M83). The same was the case when cerebellar extracts from a case of multiple system atrophy with type II α-synuclein filaments were administered intraperitoneally, intravenously or intramuscularly. We observed abundant immunoreactivity for pS129 α-synuclein in nerve cells and severe motor impairment, resulting in hindlimb paralysis and shortened lifespan. Filaments immunoreactive for pS129 α-synuclein were in evidence. A 70% loss of motor neurons was present five months after an intraperitoneal injection of assembled A53T α-synuclein or cerebellar extract with type II α-synuclein filaments from an individual with a neuropathologically confirmed diagnosis of multiple system atrophy. Microglial cells changed from a predominantly ramified to a dystrophic appearance. Taken together, these findings establish a close relationship between the formation of α-synuclein inclusions in nerve cells and neurodegeneration, accompanied by a shift in microglial cell morphology. Propagation of α-synuclein inclusions depended on the characteristics of both seeds and transgenically expressed protein.


Assuntos
Doenças Neurodegenerativas/patologia , alfa-Sinucleína/metabolismo , alfa-Sinucleína/farmacologia , Idoso , Animais , Animais Geneticamente Modificados , Membro Posterior , Humanos , Imuno-Histoquímica , Masculino , Camundongos Mutantes Neurológicos , Microglia/patologia , Neurônios Motores/patologia , Transtornos dos Movimentos/patologia , Atrofia de Múltiplos Sistemas/patologia , Mutação , Doenças Neurodegenerativas/induzido quimicamente , Neurônios/metabolismo , Paralisia/induzido quimicamente , Paralisia/patologia , alfa-Sinucleína/administração & dosagem
3.
Neurology ; 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34050004

RESUMO

OBJECTIVE: To determine the variability in pediatric death by neurologic criteria (DNC) protocols between US pediatric institutions and compared to the 2011 DNC guidelines. METHODS: Cross-sectional study of DNC protocols obtained from pediatric institutions in the United States (US) via regional organ procurement organizations. Protocols were evaluated across five domains: general DNC procedures, prerequisites, neurologic examination, apnea testing and ancillary testing. Descriptive statistics compared protocols to each other and the 2011 guidelines. RESULTS: One hundred and thirty protocols were analyzed with 118 dated after publication of the 2011 guidelines. Of those 118 protocols, identification of a mechanism of irreversible brain injury was required in 97%, while 67% required an observation period after acute brain injury before DNC evaluation. Most protocols required guideline-based prerequisites such as exclusion of hypotension (94%), hypothermia (97%), and metabolic derangements (92%). On neurologic examination, 91% required a lack of responsiveness, 93% no response to noxious stimuli, and 99% loss of brainstem reflexes. 84% of protocols required the guideline-recommened two apnea tests. CO2 targets were consistent with guidelines in 64%. Contrary to guidelines, fifteen percent required ancillary testing for all patients and 15% permitted ancillary studies that are not validated in pediatrics. CONCLUSIONS: and Relevance: Variability exists between pediatric institutional DNC protocols in all domains of DNC determination, especially with respect to apnea and ancillary testing. Better alignment of DNC protocols with national guidelines may improve the consistency and accuracy of DNC determination.

4.
Pediatr Dent ; 43(2): 129-132, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33892838

RESUMO

Purpose: The purpose of this study was to compare the safety of three different sedation regimens for pediatric dental procedures to examine the safety of intranasal dexmedetomidine paired with nitrous oxide (N2O). Methods: This was a retrospective chart review of 149 three-to six-year-old healthy patients who underwent sedation to complete dental treatment. Forty-nine patients received intranasal dexmedetomidine with nitrous oxide (DEXNO), 47 received oral midazolam with nitrous oxide (MIDNO), and 53 received oral midazolam and oral hydroxyzine with nitrous oxide (MIDHYXNO). Demographic data, procedural times, vital signs, and adverse events were recorded. Results: No patients in any of the three groups experienced major adverse events. All groups experienced some degree of hypotension. One of the 49 DEXNO cases experienced bradycardia intraoperatively. No cases required clinical intervention. Conclusion: This pilot study suggested that intranasal dexmedetomidine with nitrous oxide is a safe sedation regimen for pediatric procedures, comparable to combinations of oral midazolam with nitrous oxide and oral midazolam and oral hydroxyzine with nitrous oxide.


Assuntos
Anestesia Dentária , Dexmedetomidina , Criança , Sedação Consciente , Dexmedetomidina/efeitos adversos , Humanos , Hipnóticos e Sedativos/efeitos adversos , Óxido Nitroso/efeitos adversos , Projetos Piloto , Estudos Retrospectivos
5.
ACS Chem Neurosci ; 12(11): 1885-1893, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-33689290

RESUMO

Aggregated tau protein is a core pathology present in several neurodegenerative diseases. Therefore, the development and application of positron emission tomography (PET) imaging radiotracers that selectively bind to aggregated tau in fibril form is of importance in furthering the understanding of these disorders. While radiotracers used in human PET studies offer invaluable insight, radiotracers that are also capable of visualizing tau fibrils in animal models are important tools for translational research into these diseases. Herein, we report the synthesis and characterization of a novel library of compounds based on the phenyl/pyridinylbutadienylbenzothiazoles/benzothiazolium (PBB3) backbone developed for this application. From this library, we selected the compound LM229, which binds to recombinant tau fibrils with high affinity (Kd = 3.6 nM) and detects with high specificity (a) pathological 4R tau aggregates in living cultured neurons and mouse brain sections from transgenic human P301S tau mice, (b) truncated human 151-351 3R (SHR24) and 4R (SHR72) tau aggregates in transgenic rat brain sections, and (c) tau neurofibrillary tangles in brain sections from Alzheimer's disease (3R/4R tau) and progressive supranuclear palsy (4R tau). With LM229 also shown to cross the blood-brain barrier in vivo and its effective radiolabeling with the radioisotope carbon-11, we have established a novel platform for PET translational studies using rodent transgenic tau models.


Assuntos
Doença de Alzheimer , Proteínas tau , Doença de Alzheimer/diagnóstico por imagem , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Camundongos , Camundongos Transgênicos , Emaranhados Neurofibrilares/metabolismo , Tomografia por Emissão de Pósitrons , Ratos , Ratos Transgênicos , Proteínas tau/metabolismo
7.
JAC Antimicrob Resist ; 2(3): dlaa065, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34223022

RESUMO

OBJECTIVES: To synthesize current evidence for the effectiveness of interventions to ensure the timely review of antibiotics in acute care hospitals. METHODS: Five databases were searched from 1 January 2015 to 8 March 2019 for studies in English, focused on the timely review of antibiotics in acute care hospitals. Randomized controlled trials, non-randomized studies, case-control and cohort study designs were eligible. Intervention strategies were categorized according to the Cochrane Effective Practice and Organisation of Care taxonomy of health interventions, then mapped to the intervention functions of the behaviour change wheel. RESULTS: Fourteen studies were included. Most studies (11 out of 14) were conducted in single sites. Nine out of 14 reported intervention delivery by more than one healthcare professional. Physicians were the main targets of interventions in all studies. Thirteen out of 14 studies tested interventions comprising more than one strategy. The three most commonly utilized strategies within interventions were clinical practice guidelines, audit and feedback, and educational materials. Only one study employed theory in intervention evaluation. Reported interventions led to timely review and switch of IV antibiotic therapy, and shortened durations of overall antibiotic therapy. CONCLUSIONS: Interventions to improve the review of antibiotics were found to be effective in the short to medium term, with limited evidence of long-term sustainability in multiple sites. Future research may benefit from the application of theory to intervention design and detailed specifications of interventions to aid their easy replication and implementation in different contexts.

8.
Bone Marrow Transplant ; 55(4): 780-786, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31664185

RESUMO

We compared CMV outcomes of three prophylactic approaches used for CBT and haploidentical cord transplants from December 2009 through 2018: letermovir (n = 32) through day 100 post transplant, "valacyclovir day 100" (valacyclovir 2 g orally three times daily through day 100) (n = 60), and "valacyclovir hospital discharge" (valacyclovir 2 g orally three times daily through hospital discharge then acyclovir 800 mg twice daily) (n = 41). Through day 100, none in the letermovir group, six (10%) in the "valacyclovir day 100," and nine (22%) in the "valacyclovir hospital discharge" group required CMV directed treatment (p = 0.005 and 0.06 comparing letermovir to "valacyclovir hospital discharge" and "valacyclovir day 100"). Fewer patients in the letermovir group (n = 7, 22%) had any CMV reactivation versus the "valacyclovir day 100" group (n = 20, 33%) versus the "valacyclovir hospital discharge" group (n = 23, 57%) (p = 0.003 and 0.21 comparing letermovir to "valacyclovir hospital discharge" and "valacyclovir day 100"). Among patients not reactivating CMV before 100 days, reactivation rates between day 100 and 180 were higher in the letermovir and "valacyclovir day 100" groups than the "valacyclovir hospital discharge" group. Letermovir is safe and effective compared with alternative prophylaxis approaches following CBT through day 100. Reactivation and monitoring after day 100 remain potential concerns.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Infecções por Citomegalovirus , Acetatos , Adulto , Antivirais/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/prevenção & controle , Sangue Fetal , Humanos , Quinazolinas
9.
Acta Neuropathol Commun ; 7(1): 44, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30885267

RESUMO

A pathological pathway leading from soluble monomeric to insoluble filamentous Tau is characteristic of many human neurodegenerative diseases, which also exhibit dysfunction and death of brain cells. However, it is unknown how the assembly of Tau into filaments relates to cell loss. To study this, we first used a mouse line transgenic for full-length human mutant P301S Tau to investigate the temporal relationship between Tau assembly into filaments, assessed using anti-Tau antibody AT100, and motor neuron numbers, in the lumbar spinal cord. AT100 immunoreactivity preceded nerve cell loss. Murine Tau did not contribute significantly to either Tau aggregation or neurodegeneration. To further study the relevance of filament formation for neurodegeneration, we deleted hexapeptides 275VQIINK280 and 306VQIVYK311, either singly or in combination, from human 0N4R Tau with the P301S mutation. These hexapeptides are essential for the assembly of Tau into filaments. Homozygous mice transgenic for P301S Tau with the hexapeptide deletions, which expressed Tau at a similar level to the heterozygous line transgenic for P301S Tau, had a normal lifespan, unlike mice from the P301S Tau line. The latter had significant levels of sarkosyl-insoluble Tau in brain and spinal cord, and exhibited neurodegeneration. Mice transgenic for P301S Tau with the hexapeptide deletions failed to show significant levels of sarkosyl-insoluble Tau or neurodegeneration. Recombinant P301S Tau with the hexapeptide deletions failed to form ß-sheet structure and filaments following incubation with heparin. Taken together, we conclude that ß-sheet assembly of human P301S Tau is necessary for neurodegeneration in transgenic mice.


Assuntos
Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Medula Espinal/patologia , Tauopatias/genética , Tauopatias/patologia , Proteínas tau/genética , Animais , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
10.
Neurobiol Dis ; 127: 323-338, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30905766

RESUMO

The assembly of tau protein into abnormal filaments and brain cell degeneration are characteristic of a number of human neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia and parkinsonism linked to chromosome 17. Several murine models have been generated to better understand the mechanisms contributing to tau assembly and neurodegeneration. Taking advantage of the more elaborate central nervous system and higher cognitive abilities of the rat, we generated a model expressing the longest human tau isoform (2N4R) with the P301S mutation. This transgenic rat line, R962-hTau, exhibits the main features of human tauopathies, such as: age-dependent increase in inclusions comprised of aggregated-tau, neuronal loss, global neurodegeneration as reflected by brain atrophy and ventricular dilation, alterations in astrocytic and microglial morphology, and myelin loss. In addition, substantial deficits across multiple memory and learning paradigms, including novel object recognition, fear conditioning and Morris water maze tasks, were observed at the time of advanced tauopathy. These results support the concept that progressive tauopathy correlates with brain atrophy and cognitive impairment.


Assuntos
Encéfalo/patologia , Disfunção Cognitiva/metabolismo , Tauopatias/metabolismo , Proteínas tau/metabolismo , Animais , Encéfalo/metabolismo , Disfunção Cognitiva/genética , Disfunção Cognitiva/patologia , Modelos Animais de Doenças , Corpos de Inclusão/metabolismo , Corpos de Inclusão/patologia , Ratos , Ratos Transgênicos , Tauopatias/genética , Tauopatias/patologia , Proteínas tau/genética
11.
Psychol Rep ; 122(4): 1529-1549, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29914343

RESUMO

The Conscientious Responders Scale is a five-item embeddable validity scale that differentiates between conscientious and indiscriminate responding in personality-questionnaire data (CR & IR). This investigation presents further evidence of its validity and generalizability across two experiments. Study 1 tests its sensitivity to questionnaire length, a known cause of IR, and tries to provoke IR by manipulating psychological reactance. As expected, short questionnaires produced higher Conscientious Responders Scale scores than long questionnaires, and Conscientious Responders Scale scores were unaffected by reactance manipulations. Study 2 tests concerns that the Conscientious Responders Scale's unusual item content could potentially irritate and baffle responders, ironically increasing rates of IR. We administered two nearly identical questionnaires: one with an embedded Conscientious Responders Scale and one without the Conscientious Responders Scale. Psychometric comparisons revealed no differences across questionnaires' means, variances, interitem response consistencies, and Cronbach's alphas. In sum, the Conscientious Responders Scale is highly sensitive to questionnaire length-a known correlate of IR-and can be embedded harmlessly in questionnaires without provoking IR or changing the psychometrics of other measures.


Assuntos
Personalidade , Inquéritos e Questionários , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Determinação da Personalidade , Psicometria , Reprodutibilidade dos Testes , Adulto Jovem
12.
Br J Health Psychol ; 24(1): 66-87, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30221433

RESUMO

OBJECTIVES: In an innovative approach to improve the contribution of health psychology to public health we have analysed the presence and nature of affect within the visual materials deployed in antimicrobial stewardship interventions targeting the public identified through systematic review. DESIGN: A qualitative analysis focused on the affective content of visual materials garnered from a systematic review of antibiotic stewardship (k = 20). METHODS: A novel method was devised drawing on concepts from semiotics to analyse the affective elements within intervention materials. RESULTS: Whilst all studies examined tacitly rely on affect, only one sought to explicitly deploy affect. Three thematic categories of affect are identified within the materials in which specific ideological machinery is deployed: (1) monsters, bugs, and superheroes; (2) responsibility, threat, and the misuse/abuse of antibiotics; (3) the figure of the child. CONCLUSIONS: The study demonstrates how affect is a present but tacit communication strategy of antimicrobial stewardship interventions but has not - to date - been adequately theorized or explicitly considered in the intervention design process. Certain affective features were explored in relation to the effectiveness of antimicrobial resistance interventions and warrant further investigation. We argue that further research is needed to systematically illuminate and capitalize upon the use of affect to effect behaviour change concerning antimicrobial stewardship. Statement of contribution What is already known on this subject? The (mis)use of antibiotics and consequent risk of antimicrobial resistance is a critical public health problem. If sufficient action is not taken, global society will face the 'post-antibiotic' era, in which common infections will lead to death for many millions. Key desirable behavioural changes are decreased patient demands for antibiotics, use of them for targeted purposes alone, and compliance with prescribed dosing. There is a growth of interest in the role of affect in mass media interventions designed to engage publics and produce health-related behavioural change. What does this study add? This article presents a novel analytic approach to understanding and intervening within behaviour change in public health that may complement other types of analysis. We present findings specifically from an 'affective' analysis based on semiotics in which we critically interrogated the visual imagery being deployed in mass media public health interventions concerning antimicrobial stewardship. Three thematic categories of affect are identified within the materials in which specific ideological machinery is deployed and that demonstrate some association with intervention effectiveness worthy of further investigation and testing.


Assuntos
Gestão de Antimicrobianos , Recursos Audiovisuais , Comportamentos Relacionados com a Saúde , Meios de Comunicação de Massa , Comunicação Persuasiva , Humanos , Saúde Pública
13.
Artigo em Inglês | MEDLINE | ID: mdl-30534365

RESUMO

Background: Carbapenemase Producing Enterobacteriaceae (CPE) has spread rapidly and presents a growing challenge in antimicrobial resistance (AMR) management internationally. Screening for CPE may involve a rectal swab, there are limited treatment options for affected patients, and colonised patients are cared for in isolation to protect others. These measures are sound infection prevention precautions; however, the acceptability of CPE screening and its consequences are currently unknown.The aim of this study was 'To determine factors influencing acceptability of CPE screening from the perspectives of nursing staff and the general public.' Methods: National cross-sectional surveys of nursing staff (n = 450) and the general public (n = 261). The Theoretical Domains Framework (TDF) guided data collection and analysis. Regression modelling was used to identify factors that predicted acceptability of CPE screening. Results: For nursing staff, the following predictor variables were significant: intention to conduct CPE screening (OR 14.19, CI 5.14-39.22); belief in the severity of the consequences of CPE (OR 7.13, CI 3.26-15.60); knowledge of hospital policy for screening (OR 3.04, CI 1.45-6.34); preference to ask patients to take their own rectal swab (OR 2.89, CI 1.39-6.0); awareness that CPE is an organism of growing concern (OR 2.44, CI 1.22-4.88). The following predictor variables were significant for the general public: lack of knowledge of AMR (ß - .11, p = .01); social influences (ß .14, p = .032); social norms (ß .21p = .00); acceptability of being isolated if colonised (ß .22, p = .000), beliefs about the acceptability of rectal swabbing (ß .15, p = .00), beliefs about the impact of careful explanation about CPE screening from a health professional (ß .32, p = .00).Integrating results from staff and public perspectives points to the importance of knowledge of AMR, environmental resources, and social influences in shaping acceptability. Conclusions: This is the first study to systematically examine the acceptability of CPE screening across nursing staff and the public. The use of TDF enabled identification of the mechanisms of action, or theoretical constructs, likely to be important in understanding and changing CPE related behaviour amongst professionals and public alike.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Infecção Hospitalar/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Programas de Rastreamento , Recursos Humanos de Enfermagem/psicologia , Adolescente , Adulto , Idoso , Infecção Hospitalar/microbiologia , Estudos Transversais , Infecções por Enterobacteriaceae/prevenção & controle , Feminino , Pesquisa sobre Serviços de Saúde , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Reto/microbiologia , Inquéritos e Questionários , Adulto Jovem
14.
Infect Control Hosp Epidemiol ; 39(12): 1449-1456, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30526716

RESUMO

OBJECTIVE: To synthesize the existing evidence base of systematic reviews of interventions to improve healthcare worker (HCW) hand hygiene compliance (HHC). METHODS: PRISMA guidelines were followed, and 10 information sources were searched in September 2017, with no limits to language or date of publication, and papers were screened against inclusion criteria for relevance. Data were extracted and risk of bias was assessed. RESULTS: Overall, 19 systematic reviews (n=20 articles) were included. Only 1 article had a low risk of bias. Moreover, 15 systematic reviews showed positive effects of interventions on HCW HHC, whereas 3 reviews evaluating monitoring technology did not. Findings regarding whether multimodal rather than single interventions are preferable were inconclusive. Targeting social influence, attitude, self-efficacy, and intention were associated with greater effectiveness. No clear link emerged between how educational interventions were delivered and effectiveness. CONCLUSIONS: This is the first systematic review of systematic reviews of interventions to improve HCW HHC. The evidence is sufficient to recommend the implementation of interventions to improve HCW HHC (except for monitoring technology), but it is insufficient to make specific recommendations regarding the content or how the content should be delivered. Future research should rigorously apply behavior change theory, and recommendations should be clearly described with respect to intervention content and how it is delivered. Such recommendations should be tested for longer terms using stronger study designs with clearly defined outcomes.


Assuntos
Infecção Hospitalar/prevenção & controle , Higiene das Mãos/normas , Pessoal de Saúde , Fidelidade a Diretrizes , Humanos , Revisões Sistemáticas como Assunto
15.
Br J Health Psychol ; 23(4): 804-819, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29804314

RESUMO

OBJECTIVES: Changing public awareness of antimicrobial resistance (AMR) represents a global public health priority. A systematic review of interventions that targeted public AMR awareness and associated behaviour was previously conducted. Here, we focus on identifying the active content of these interventions and explore potential mechanisms of action. METHODS: The project took a novel approach to intervention mapping utilizing the following steps: (1) an exploration of explicit and tacit theory and theoretical constructs within the interventions using the Theoretical Domains Framework (TDFv2), (2) retrospective coding of behaviour change techniques (BCTs) using the BCT Taxonomy v1, and (3) an investigation of coherent links between the TDF domains and BCTs across the interventions. RESULTS: Of 20 studies included, only four reported an explicit theoretical basis to their intervention. However, TDF analysis revealed that nine of the 14 TDF domains were utilized, most commonly 'Knowledge' and 'Environmental context and resources'. The BCT analysis showed that all interventions contained at least one BCT, and 14 of 93 (15%) BCTs were coded, most commonly 'Information about health consequences', 'Credible source', and 'Instruction on how to perform the behaviour'. CONCLUSIONS: We identified nine relevant TDF domains and 14 BCTs used in these interventions. Only 15% of BCTs have been applied in AMR interventions thus providing a clear opportunity for the development of novel interventions in this context. This methodological approach provides a useful way of retrospectively mapping theoretical constructs and BCTs when reviewing studies that provide limited information on theory and intervention content. Statement of contribution What is already known on this subject? Evidence of the effectiveness of interventions that target the public to engage them with AMR is mixed; the public continue to show poor knowledge and misperceptions of AMR. Little is known about the common, active ingredients of AMR interventions targeting the public and information on explicit theoretical content is sparse. Information on the components of AMR public health interventions is urgently needed to enable the design of effective interventions to engage the public with AMR stewardship behaviour. What does this study add? The analysis shows very few studies reported any explicit theoretical basis to the interventions they described. Many interventions share common components, including core mechanisms of action and behaviour change techniques. The analysis suggests components of future interventions to engage the public with AMR.


Assuntos
Farmacorresistência Bacteriana , Comportamentos Relacionados com a Saúde , Comunicação em Saúde/métodos , Conhecimentos, Atitudes e Prática em Saúde , Promoção da Saúde/métodos , Humanos , Masculino , Estudos Retrospectivos
16.
J Antimicrob Chemother ; 73(6): 1464-1478, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29554263

RESUMO

Background: A global antimicrobial resistance (AMR) awareness intervention targeting the general public has been prioritized. Objectives: To evaluate the effectiveness of interventions that aim to change AMR awareness and subsequent stewardship behaviours amongst the public. Methods: Five databases were searched between 2000 and 2016 for interventions to change the public's AMR awareness and/or antimicrobial stewardship behaviours. Study designs meeting the Cochrane Effective Practice and Organization of Care (EPOC) criteria, non-controlled before-and-after studies and prospective cohort studies were considered eligible. Participants recruited from healthcare settings and studies measuring stewardship behaviours of healthcare professionals were excluded. Quality of studies was assessed using EPOC risk of bias criteria. Data were extracted and synthesized narratively. Registration: PROSPERO international prospective register of systematic reviews (PROSPERO 2016: CRD42016050343). Results: Twenty studies were included in the review with nine meeting the EPOC criteria. The overall risk of bias was high. Nineteen studies were conducted in high-income countries. Mass media interventions were most common (n = 7), followed by school-based (n = 6) and printed material interventions (n = 6). Seventeen studies demonstrated a significant effect on changing knowledge, attitudes or the public's antimicrobial stewardship behaviours. Analysis showed that interventions targeting schoolchildren and parents have notable potential, but for the general public the picture is less clear. Conclusions: Our work provides an in-depth examination of the effectiveness of AMR interventions for the public. However, the studies were heterogeneous and the quality of evidence was poor. Well-designed, experimental studies on behavioural outcomes of such interventions are required.


Assuntos
Gestão de Antimicrobianos/métodos , Farmacorresistência Bacteriana , Conhecimentos, Atitudes e Prática em Saúde , Saúde Pública/métodos , Antibacterianos/farmacologia , Gestão de Antimicrobianos/estatística & dados numéricos , Ensaios Clínicos como Assunto , Humanos , Estudos Prospectivos , Saúde Pública/estatística & dados numéricos
17.
Lancet Infect Dis ; 18(5): e159-e171, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29100898

RESUMO

Evidence-based guidance for national infection prevention and control (IPC) programmes is needed to support national and global capacity building to reduce health-care-associated infection and antimicrobial resistance. In this systematic review we investigate evidence on the effectiveness of IPC interventions implemented at national or subnational levels to inform the development of WHO guidelines on the core components of national IPC programmes. We searched CENTRAL, CINAHL, Embase, MEDLINE, and WHO IRIS databases for publications between Jan 1, 2000, and April 19, 2017. 29 studies that met the eligibility criteria (ie, economic evaluations, cluster-randomised trials, non-randomised trials, controlled before-and-after studies, and interrupted time-series studies exploring the effective of these interventions) were categorised according to intervention type: multimodal, care bundles, policies, and surveillance, monitoring, and feedback. Evidence of effectiveness was found in all categories but the best quality evidence was on multimodal interventions and surveillance, monitoring, and feedback. We call for improvements in study design, reporting of research, and quality of evidence particularly from low-income countries, to strengthen the uptake and international relevance of IPC interventions.


Assuntos
Controle de Doenças Transmissíveis/economia , Controle de Doenças Transmissíveis/normas , Países Desenvolvidos , Política de Saúde , Humanos , Vigilância da População , Organização Mundial da Saúde
18.
Stem Cell Reports ; 9(4): 1139-1151, 2017 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-28943254

RESUMO

Satellite cells are skeletal-muscle-specific stem cells that are activated by injury to proliferate, differentiate, and fuse to enable repair. SOX7, a member of the SRY-related HMG-box family of transcription factors is expressed in quiescent satellite cells. To elucidate SOX7 function in skeletal muscle, we knocked down Sox7 expression in embryonic stem cells and primary myoblasts and generated a conditional knockout mouse in which Sox7 is excised in PAX3+ cells. Loss of Sox7 in embryonic stem cells reduced Pax3 and Pax7 expression. In vivo, conditional knockdown of Sox7 reduced the satellite cell population from birth, reduced myofiber caliber, and impaired regeneration after acute injury. Although Sox7-deficient primary myoblasts differentiated normally, impaired myoblast fusion and increased sensitivity to apoptosis in culture and in vivo were observed. Taken together, these results indicate that SOX7 is dispensable for myogenesis but is necessary to promote satellite cell development and survival.


Assuntos
Diferenciação Celular/genética , Autorrenovação Celular/genética , Fatores de Transcrição SOXF/genética , Células Satélites de Músculo Esquelético/citologia , Células Satélites de Músculo Esquelético/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/genética , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Expressão Gênica , Técnicas de Inativação de Genes , Camundongos , Camundongos Knockout , Desenvolvimento Muscular , Fibras Musculares Esqueléticas/fisiologia , Mioblastos/citologia , Mioblastos/metabolismo , Regeneração
19.
MMWR Morb Mortal Wkly Rep ; 66(13): 366-373, 2017 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-28384133

RESUMO

BACKGROUND: In collaboration with state, tribal, local, and territorial health departments, CDC established the U.S. Zika Pregnancy Registry (USZPR) in early 2016 to monitor pregnant women with laboratory evidence of possible recent Zika virus infection and their infants. METHODS: This report includes an analysis of completed pregnancies (which include live births and pregnancy losses, regardless of gestational age) in the 50 U.S. states and the District of Columbia (DC) with laboratory evidence of possible recent Zika virus infection reported to the USZPR from January 15 to December 27, 2016. Birth defects potentially associated with Zika virus infection during pregnancy include brain abnormalities and/or microcephaly, eye abnormalities, other consequences of central nervous system dysfunction, and neural tube defects and other early brain malformations. RESULTS: During the analysis period, 1,297 pregnant women in 44 states were reported to the USZPR. Zika virus-associated birth defects were reported for 51 (5%) of the 972 fetuses/infants from completed pregnancies with laboratory evidence of possible recent Zika virus infection (95% confidence interval [CI] = 4%-7%); the proportion was higher when restricted to pregnancies with laboratory-confirmed Zika virus infection (24/250 completed pregnancies [10%, 95% CI = 7%-14%]). Birth defects were reported in 15% (95% CI = 8%-26%) of fetuses/infants of completed pregnancies with confirmed Zika virus infection in the first trimester. Among 895 liveborn infants from pregnancies with possible recent Zika virus infection, postnatal neuroimaging was reported for 221 (25%), and Zika virus testing of at least one infant specimen was reported for 585 (65%). CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: These findings highlight why pregnant women should avoid Zika virus exposure. Because the full clinical spectrum of congenital Zika virus infection is not yet known, all infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy should receive postnatal neuroimaging and Zika virus testing in addition to a comprehensive newborn physical exam and hearing screen. Identification and follow-up care of infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy and infants with possible congenital Zika virus infection can ensure that appropriate clinical services are available.


Assuntos
Anormalidades Congênitas/virologia , Feto/virologia , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus , Encéfalo/anormalidades , Encéfalo/virologia , Doenças do Sistema Nervoso Central/epidemiologia , Doenças do Sistema Nervoso Central/virologia , Anormalidades Congênitas/epidemiologia , Anormalidades do Olho/epidemiologia , Anormalidades do Olho/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Microcefalia/epidemiologia , Microcefalia/virologia , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/virologia , Gravidez , Sistema de Registros , Estados Unidos/epidemiologia , Zika virus/isolamento & purificação , Infecção por Zika virus/epidemiologia
20.
Health Technol Assess ; 21(5): 1-164, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28145220

RESUMO

BACKGROUND: Men who have sex with men (MSM) experience significant inequalities in health and well-being. They are the group in the UK at the highest risk of acquiring a human immunodeficiency virus (HIV) infection. Guidance relating to both HIV infection prevention, in general, and individual-level behaviour change interventions, in particular, is very limited. OBJECTIVES: To conduct an evidence synthesis of the clinical effectiveness of behaviour change interventions to reduce risky sexual behaviour among MSM after a negative HIV infection test. To identify effective components within interventions in reducing HIV risk-related behaviours and develop a candidate intervention. To host expert events addressing the implementation and optimisation of a candidate intervention. DATA SOURCES: All major electronic databases (British Education Index, BioMed Central, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Educational Resource Index and Abstracts, Health and Medical Complete, MEDLINE, PsycARTICLES, PsycINFO, PubMed and Social Science Citation Index) were searched between January 2000 and December 2014. REVIEW METHODS: A systematic review of the clinical effectiveness of individual behaviour change interventions was conducted. Interventions were examined using the behaviour change technique (BCT) taxonomy, theory coding assessment, mode of delivery and proximity to HIV infection testing. Data were summarised in narrative review and, when appropriate, meta-analysis was carried out. Supplemental analyses for the development of the candidate intervention focused on post hoc realist review method, the assessment of the sequential delivery and content of intervention components, and the social and historical context of primary studies. Expert panels reviewed the candidate intervention for issues of implementation and optimisation. RESULTS: Overall, trials included in this review (n = 10) demonstrated that individual-level behaviour change interventions are effective in reducing key HIV infection risk-related behaviours. However, there was considerable clinical and methodological heterogeneity among the trials. Exploratory meta-analysis showed a statistically significant reduction in behaviours associated with high risk of HIV transmission (risk ratio 0.75, 95% confidence interval 0.62 to 0.91). Additional stratified analyses suggested that effectiveness may be enhanced through face-to-face contact immediately after testing, and that theory-based content and BCTs drawn from 'goals and planning' and 'identity' groups are important. All evidence collated in the review was synthesised to develop a candidate intervention. Experts highlighted overall acceptability of the intervention and outlined key ways that the candidate intervention could be optimised to enhance UK implementation. LIMITATIONS: There was a limited number of primary studies. All were from outside the UK and were subject to considerable clinical, methodological and statistical heterogeneity. The findings of the meta-analysis must therefore be treated with caution. The lack of detailed intervention manuals limited the assessment of intervention content, delivery and fidelity. CONCLUSIONS: Evidence regarding the effectiveness of behaviour change interventions suggests that they are effective in changing behaviour associated with HIV transmission. Exploratory stratified meta-analyses suggested that interventions should be delivered face to face and immediately after testing. There are uncertainties around the generalisability of these findings to the UK setting. However, UK experts found the intervention acceptable and provided ways of optimising the candidate intervention. FUTURE WORK: There is a need for well-designed, UK-based trials of individual behaviour change interventions that clearly articulate intervention content and demonstrate intervention fidelity. STUDY REGISTRATION: The study is registered as PROSPERO CRD42014009500. FUNDING: The National Institute for Health Research Health Technology Assessment programme.


Assuntos
Terapia Comportamental/métodos , Infecções por HIV/prevenção & controle , Homossexualidade Masculina/psicologia , Comportamento Sexual/psicologia , Análise Custo-Benefício , Competência Cultural , Objetivos , Humanos , Intenção , Masculino , Identificação Social , Apoio Social , Medicina Estatal , Reino Unido
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