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1.
Perspect Public Health ; 143(3): 151-155, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37132024

RESUMO

AIMS: To propose that the language and concepts in public mental health are often medicalised and to suggest that the power threat meaning framework (PTMF), can be a useful resource for those wishing to take a de-medicalising approach. METHOD: Examples of medicalisation from the literature and from practice are discussed and key constructs in the PTMF are explained, drawing from the report which presented its research base. RESULTS: Examples of medicalisation in public mental health include: the uncritical use of psychiatric diagnostic categories; the 'illness like any other' approach in anti-stigma campaigns; and the implicit privileging of biology in the biopsychosocial model. The negative operations of power in society are seen as posing threats to human needs and people make sense of such situations in varied ways, though there are some commonalities. This gives rise to culturally available and bodily enabled threat responses which serve a variety of functions. From a medicalised perspective, these responses to threat are characteristically seen as 'symptoms' of underlying disorders. The PTMF is both a conceptual framework and a practical tool that can be used by individuals, groups and communities. CONCLUSION: Consistent with social epidemiological research, prevention efforts should focus on preventing adversity rather than 'disorders' but the added value of the PTMF is that varied problems can be understood in an integrated manner as responses to a variety of threats whose functions could be met in different ways. Its message that mental distress is often a response to adversity is comprehensible to the public and can be communicated in an accessible way.


Assuntos
Transtornos Mentais , Saúde Mental , Humanos , Transtornos Mentais/psicologia , Estigma Social , Saúde Pública
2.
Water Res ; 173: 115532, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32059128

RESUMO

Saline-alkaline lakes of the East African Rift are known to have an extremely high primary production supporting a potent carbon cycle. To date, a full description of carbon pools in these lakes is still missing. More specifically, there is not detailed information on the quality of dissolved organic matter (DOM), the main carbon energy source for heterotrophs prokaryotes. We report the first exhaustive description of DOM molecular properties in the water column of a meromictic saline-alkaline lake of the East African Rift. DOM availability, fate and origin were studied either quantitatively, in terms of dissolved organic carbon (DOC) and nitrogen (DON) or qualitatively, in terms of optical properties (absorbance) and molecular characterization of solid-phase extracted DOM (SPE-DOM) through negative electrospray ionization Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). DOM availability was high (DOC ∼ 8.1 mM in surface waters) and meromixis imprinted a severe quantitative and qualitative change on DOM pool. At the surface, DOM was rich in aliphatic and moderately in aromatic molecules and thus mirroring autochthonous microbial production together with photodegradation. At the bottom changes were extreme: DOC increased up to 5 times (up to 50 mM) and, molecular signature drifted to saturated, reduced and non-aromatic DOM suggesting intense microbial activity within organic sediments. At the chemocline, DOC was retained indicating that this interface is a highly reactive layer in terms of DOM processing. These findings underline that saline-alkaline lakes of the East African Rift are carbon processing hot spots and their investigation may broaden our understanding of carbon cycling in inland waters at large.


Assuntos
Carbono , Lagos , Ciclo do Carbono , Espectrometria de Massas , Nitrogênio
4.
Eur J Clin Nutr ; 72(12): 1603-1619, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30166640

RESUMO

BACKGROUND: In view of the ongoing debate on "chronic malnutrition" and the concept of "stunting" as "a better measure than underweight of the cumulative effects of undernutrition and infection (WHO)", we translate, briefly comment and re-publish three seminal historic papers on catch-up growth following re-feeding after severe food restriction of German children during and after World War I. The observations were published in 1920 and 1922, and appear to be of particular interest to the modern nutritionist. RESULTS: The papers of Abderhalden (1920) and Bloch (1920) describe German children of all social strata who were born shortly before World War I, and raised in apparently "normal" families. After severe long-standing undernutrition, they participated in an international charity program. They experienced exceptional catch-up growth in height of 3-5 cm within 6-8 weeks. Goldstein (1922) observed 512 orphans and children from underprivileged families. Goldstein described very different growth patterns. These children were much shorter (mean height between -2.0 and -2.8 SDS, modern WHO reference). They mostly failed to catch-up in height, but tended to excessively increase in weight particularly during adolescence. CONCLUSION: Whereas Abderhalden and Bloch illustrate rapid height catch-up in children from intact social background, Goldstein's observations in orphans and children from poor social background parallel the growth patterns observed in children of modern middle and low-income countries. The historic observations question the current concept of stunting as prima facie evidence of malnutrition and chronic infection, and support the view that "the child's longitudinal growth is largely independent of the extent and nature of the diet".


Assuntos
Dieta/história , Comportamento Alimentar/fisiologia , Transtornos do Crescimento/história , Crescimento , Desnutrição/história , Estatura , Peso Corporal , Criança , Estudos de Coortes , Feminino , Alemanha , Transtornos do Crescimento/fisiopatologia , História do Século XX , Humanos , Masculino , Desnutrição/fisiopatologia , Populações Vulneráveis/estatística & dados numéricos , I Guerra Mundial
5.
Appl Opt ; 57(21): 6061-6075, 2018 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-30118035

RESUMO

The NASA Langley airborne second-generation High Spectral Resolution Lidar (HSRL-2) uses a density-tuned field-widened Michelson interferometer to implement the HSRL technique at 355 nm. The Michelson interferometer optically separates the received backscattered light between two channels, one of which is dominated by molecular backscattering, while the other contains most of the light backscattered by particles. This interferometer achieves high and stable contrast ratio, defined as the ratio of particulate backscatter signal received by the two channels. We show that a high and stable contrast ratio is critical for precise and accurate backscatter and extinction retrievals. Here, we present retrieval equations that take into account the incomplete separation of particulate and molecular backscatter in the measurement channels. We also show how the accuracy of the contrast ratio assessment propagates to error in the optical properties. For both backscattering and extinction, larger errors are produced by underestimates of the contrast ratio (compared to overestimates), more extreme aerosol loading, and-most critically-smaller true contrast ratios. We show example results from HSRL-2 aboard the NASA ER-2 aircraft from the 2016 ORACLES field campaign in the southeast Atlantic, off the coast of Africa, during the biomass burning season. We include a case study where smoke aerosol in two adjacent altitude layers showed opposite differences in extinction- and backscatter-related Ångström exponents and a reversal of the lidar ratio spectral dependence, signatures which are shown to be consistent with a relatively modest difference in smoke particle size.

6.
Br J Oral Maxillofac Surg ; 56(2): 96-100, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29395449

RESUMO

Effusions are common among patients with disorders of the temporomandibular joint (TMJ), but publications are limited and results inconsistent about the correlation between them and important clinical variables, in particular severity of pain and degenerative disease. We organised a retrospective study of patients who presented for the evaluation and management of arthralgia of the TMJ and myofascial pain at the University of Michigan between 2011 and 2014. Inclusion criteria were: patients who had pain that was primarily arthrogenous, and coexisting myogenous pain, who had had initial non-surgical treatment, and arthroscopy of the TMJ with or without intramuscular injection of onabotulinumtoxinA (Botox,® Allegan, Weston, Fl, USA). The primary outcome variables were pain at rest as measured by visual analogue score (VAS) and the presence of degenerative disease of the joint. The secondary outcome variables included the position of the disc and whether it was perforated, signs of synovitis, maximal interincisal opening (MIO), and duration of symptoms. We studied 47 patients (94 TMJ) who met the inclusion criteria. We found no significant differences in pain at rest before or after arthroscopy, between patients with and without effusions, or in maximal MIO or duration of symptoms between the two groups. There was, however, a significant relation between effusions and degenerative joint disease. Effusions were also associated with a lower probability of the disc being in a normal position and a higher probability of anterior disc displacement without reduction.


Assuntos
Exsudatos e Transudatos/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Artralgia/diagnóstico por imagem , Artroscopia , Toxinas Botulínicas Tipo A/uso terapêutico , Feminino , Humanos , Masculino , Michigan , Pessoa de Meia-Idade , Fármacos Neuromusculares/uso terapêutico , Medição da Dor , Estudos Retrospectivos , Transtornos da Articulação Temporomandibular/terapia
7.
Aust Vet J ; 95(11): 431-436, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29076222

RESUMO

BACKGROUND: The northern hairy-nosed wombat (Lasiorhinus krefftii) is critically endangered, with only 200 individuals remaining in the wild. Individuals are rarely available for detailed pathological assessment and identification of disease threats to individuals is critically important to species conservation. CASE REPORT: Two male northern hairy-nosed wombats, part of the Richard Underwood Nature Refuge population, were presented for necropsy, 5 months apart. They were found to have succumbed to adiaspiromycosis caused by the fungus Emmonsia parva. Pathological presentations were of severe pulmonary oedema and fibrosis, and pleuritis, respectively. Characteristic fungal adiaspores were noted on histopathological examination. The wombats had concurrent variably severe ectoparasite and endoparasite burdens. CONCLUSION: These are the first reported cases of adiaspiromycosis in northern hairy-nosed wombats and the organism was associated with significant pathological changes. The rarity and the logistical challenges of presenting northern hairy-nosed wombats for pathological assessment are a challenge to identifying disease threats in this critically endangered species.


Assuntos
Chrysosporium/isolamento & purificação , Pneumopatias Fúngicas/veterinária , Marsupiais , Animais , Animais de Zoológico , Autopsia , Intestinos/parasitologia , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/patologia , Masculino , Micoses/diagnóstico , Micoses/veterinária
8.
Radiography (Lond) ; 23 Suppl 1: S58-S63, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28780954

RESUMO

OBJECTIVES: The aim of the study was to complete a collaborative review of Radiography continuing professional development (CPD) research material to support the production of European Federation of Radiographer Societies (EFRS) CPD recommendations. A meta-ethnography approach to literature review was applied focussing upon commonalities rather than discrepancies between research outcomes. This facilitated exploration of context across the geographical region of Europe with national variations in CPD governance. The seven phases of the meta-ethnographic approach were followed by two independent experienced researchers. A third researcher mediated the findings which were then explored collaboratively with the EFRS CPD working group for concordance. KEY FINDINGS: Phase seven of the meta-ethnography involved interpreting an expression of the synthesis from the previous stages. Six main corroborating themes emerged in this process and following mediation were expressed as themes; knowledge, skills & competency, needs/gap analysis, multi-layered/multi-modal, barriers and drivers; regulation vs autonomy; fostering collaboration - harnessing technology. CONCLUSION: The primary feature of CPD activity should be the resulting impact - to patients, the service, the profession and the individual; with all stakeholders working in partnership. CPD activity must be flexible/multi-modal to support the changing growth/dynamic workforce. All stakeholders should utilise communication and technology resources and make efforts to improve collaboration between the management, regulators and educators to support Radiographers to develop meaningful CPD. Health services across Europe are under increasing stress and a principal factor going forwards will be managing increasing demands on healthcare staff whilst supporting enhancement of the knowledge, skills and competency base.


Assuntos
Educação Continuada , Tecnologia Radiológica/educação , Europa (Continente) , Humanos
9.
Eur J Pain ; 21(9): 1591-1601, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28573748

RESUMO

BACKGROUND: The thermal grill illusion (TGI) refers to the perception of burning heat and often pain that arises from simultaneous cutaneous application of innocuous warm and cool stimuli. This study utilized conditioned pain modulation (CPM) to help elucidate the TGI's underlying neural mechanisms, including the debated role of ascending nociceptive signals in generating the illusion. METHODS: To trigger CPM, subjects placed the left hand in noxious cold (6 °C) water before placing the right volar forearm onto a thermal grill. Lower pain and unpleasantness ratings of the grill in this CPM run compared to those in a control run (i.e. 33 °C water) were taken as evidence of CPM. To determine whether CPM reduces noxious heat pain and illusory heat pain equally, an experimental group of subjects rated pain and unpleasantness of a grill consisting of innocuous alternating warm (42 °C) and cool (18 °C) bars, while a control group rated a grill with all bars controlled to a noxious temperature (45 °C). RESULTS: CPM produced significant and comparable reductions in pain, unpleasantness and perceived heat of both noxious heat and the TGI. CONCLUSIONS: This result suggests that the TGI results from signals in nociceptive dorsal horn convergent neurons, since CPM involves descending inhibition with high selectivity for this neuronal population. More broadly, CPM's ability to produce a shift in perceived thermal sensation of both noxious heat and the TGI from 'hot' to 'warm' implies that nociceptive signals generated by a cutaneous stimulus can contribute to its perceived thermal intensity. SIGNIFICANCE: Conditioned pain modulation reduces the perceived painfulness, unpleasantness and heat of the thermal grill illusion and noxious heat similarly. The results have important theoretical implications for both types of pain.


Assuntos
Ilusões/fisiologia , Percepção da Dor/fisiologia , Limiar da Dor/fisiologia , Dor/fisiopatologia , Sensação Térmica/fisiologia , Adolescente , Temperatura Baixa , Feminino , Temperatura Alta , Humanos , Masculino , Medição da Dor/métodos , Adulto Jovem
10.
Sci Total Environ ; 579: 1781-1793, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27939081

RESUMO

Wastewaters from oil and gas development pose largely unknown risks to environmental resources. In January 2015, 11.4ML (million liters) of wastewater (300g/L TDS) from oil production in the Williston Basin was reported to have leaked from a pipeline, spilling into Blacktail Creek, North Dakota. Geochemical and biological samples were collected in February and June 2015 to identify geochemical signatures of spilled wastewaters as well as biological responses along a 44-km river reach. February water samples had elevated chloride (1030mg/L) and bromide (7.8mg/L) downstream from the spill, compared to upstream levels (11mg/L and <0.4mg/L, respectively). Lithium (0.25mg/L), boron (1.75mg/L) and strontium (7.1mg/L) were present downstream at 5-10 times upstream concentrations. Light hydrocarbon measurements indicated a persistent thermogenic source of methane in the stream. Semi-volatile hydrocarbons indicative of oil were not detected in filtered samples but low levels, including tetramethylbenzenes and di-methylnaphthalenes, were detected in unfiltered water samples downstream from the spill. Labile sediment-bound barium and strontium concentrations (June 2015) were higher downstream from the Spill Site. Radium activities in sediment downstream from the Spill Site were up to 15 times the upstream activities and, combined with Sr isotope ratios, suggest contributions from the pipeline fluid and support the conclusion that elevated concentrations in Blacktail Creek water are from the leaking pipeline. Results from June 2015 demonstrate the persistence of wastewater effects in Blacktail Creek several months after remediation efforts started. Aquatic health effects were observed in June 2015; fish bioassays showed only 2.5% survival at 7.1km downstream from the spill compared to 89% at the upstream reference site. Additional potential biological impacts were indicated by estrogenic inhibition in downstream waters. Our findings demonstrate that environmental signatures from wastewater spills are persistent and create the potential for long-term environmental health effects.


Assuntos
Monitoramento Ambiental , Águas Residuárias/análise , Poluentes Químicos da Água/análise , North Dakota , Campos de Petróleo e Gás , Rios/química
11.
Anaesthesia ; 72(3): 328-334, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27981565

RESUMO

Despite the high number of central venous access devices inserted annually, there are limited data on the incidence of the associated procedural complications, many of which carry substantial clinical risk. This point was highlighted in the recently published Association of Anaesthetists of Great Britain and Ireland 'Safe vascular access 2016' guidelines. This trainee-led snapshot study aimed to identify the number of central venous catheter insertions and the incidence of serious complications across multiple hospital sites within a fixed two-week period. Secondary aims were to identify the availability of resources and infrastructure to facilitate safe central venous catheter insertion and management of potential complications. Fifteen hospital sites participated, completing an initial resource survey and daily identification of all adult central venous catheter insertions, with subsequent review of any complications detected. A total of 487 central venous catheter insertions were identified, of which 15 (3.1%) were associated with a significant procedural complication. The most common complication was failure of insertion, which occurred in seven (1.4%) cases. Facilities to enable safer central venous catheter insertion and manage complications varied widely between hospitals, with little evidence of standardisation of guidelines or protocols.


Assuntos
Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/métodos , Cateterismo Venoso Central/normas , Cateterismo Venoso Central/estatística & dados numéricos , Competência Clínica , Inglaterra , Pesquisas sobre Atenção à Saúde , Humanos , Incidência , Auditoria Médica/métodos , Gestão da Segurança/organização & administração , Gestão da Segurança/normas , Falha de Tratamento , Ultrassonografia de Intervenção/estatística & dados numéricos
12.
R Soc Open Sci ; 3(11): 160420, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28018620

RESUMO

The Sirius Passet Lagerstätte of North Greenland contains the first exceptionally preserved mat-ground community of the Cambrian, dominated, in terms of abundance, by trilobites but particularly characterized by iconic arthropods and lobopods, some also occurring in the Burgess shale. High-resolution photography, scanning electron imaging and elemental mapping have been carried out on a variety of specimens of the non-mineralized arthropod Campanamuta mantonae (Budd 2011 J. Syst. Palaeontol.9, 217-260 (doi:10.1080/14772019.2010.492644)) which has three-dimensional gut and muscle preservation. Results show that the guts contain a high concentration of calcium phosphate (approximating to the mineral francolite), whereas the adjacent muscles are silicified. This indicates a unique, tissue-specific taphonomy for this Cambrian taxon. We hypothesize that the precipitation of calcium phosphate in the guts occurs rapidly after death by 'crystal seed' processes in suboxic, slightly acidic conditions; critically, the gut wall remained intact during precipitation. We postulate that the calcium phosphate was derived from ingested cellular material. Silicification of the muscles followed as the localized water chemistry became saturated in silica, high in Fe2+, and low in oxygen and sulfate. We document here the unique occurrence of two distinct but mechanistically similar taphonomic pathways within a diverse suite of possibilities in an Early Cambrian Lagerstätte.

13.
J Dent Res ; 95(10): 1102-8, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27422858

RESUMO

Until recently, most clinicians and scientists believed that the experience of pain is perceptually proportional to the amount of incoming peripheral nociceptive drive due to injury or inflammation in the area perceived to be painful. However, many cases of chronic pain have defied this logic, leaving clinicians perplexed as to how patients are experiencing pain with no obvious signs of injury in the periphery. Conversely, there are patients who have a peripheral injury and/or inflammation but little or no pain. What makes some individuals experience intense pain with minimal peripheral nociceptive stimulation and others experience minimal pain with serious injury? It is increasingly well accepted in the scientific community that pain can be generated and maintained or, through other mechanisms, suppressed by changes in the central nervous system, creating a complete mismatch between peripheral nociceptive drive and perceived pain. In fact, there is no known chronic pain condition where the observed extent of peripheral damage reproducibly engenders the same level of pain across individuals. Temporomandibular disorders (TMDs) are no exception. This review focuses on the idea that TMD patients range on a continuum-from those whose pain is generated peripherally to those whose pain is centralized (i.e., generated, exacerbated, and/or maintained by central nervous system mechanisms). This article uses other centralized chronic pain conditions as a guide, and it suggests that the mechanistic variability in TMD pain etiology has prevented us from adequately treating many individuals who are diagnosed with the condition. As the field moves forward, it will be imperative to understand each person's pain from its own mechanistic standpoint, which will enable clinicians to deliver personalized medicine to TMD patients and eventually provide relief in even the most recalcitrant cases.


Assuntos
Sensibilização do Sistema Nervoso Central/fisiologia , Dor Crônica/fisiopatologia , Dor Facial/fisiopatologia , Percepção da Dor/fisiologia , Transtornos da Articulação Temporomandibular/fisiopatologia , Dor Crônica/etiologia , Odontologia Baseada em Evidências , Dor Facial/etiologia , Humanos , Transtornos da Articulação Temporomandibular/etiologia
14.
J Thromb Haemost ; 13(10): 1888-99, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26256688

RESUMO

BACKGROUND: Megakaryocytes express and store platelet factor 4 (PF4) in alpha granules. In vivo, PF4 is a clinically relevant, negative regulator of megakaryopoiesis and hematopoietic stem cell replication. These findings would suggest a regulated source of free intramedullary PF4. OBJECTIVES: Define the source of free intramedullary PF4 and its intramedullary life cycle. METHODS: We interrogated both murine and human bone marrow-derived cells during megakaryopoiesis in vitro by using confocal microscopy and enzyme-linked immunosorbent assay. With immunohistochemistry, we examined in vivo free PF4 in murine bone marrow before and after radiation injury and in the setting of megakaryocytopenia and thrombocytopenia. RESULTS: Exogenously added human PF4 is internalized by murine megakaryocytes. Human megakaryocytes similarly take up murine PF4 but not the related chemokine, platelet basic protein. Confocal microscopy shows that internalized PF4 colocalizes with endogenous PF4 in alpha granules and is available for release on thrombin stimulation. Immunohistochemistry shows free PF4 in the marrow, but not another alphagranule protein, von Willebrand factor. Free PF4 increases with radiation injury and decreases with megakaryocytopenia. Consistent with the known role of low-density lipoprotein receptor-related protein 1 in the negative paracrine effect of PF4 on megakaryopoiesis, PF4 internalization is at least partially low-density lipoprotein receptor-related protein 1 dependent. CONCLUSIONS: PF4 has a complex intramedullary life cycle with important implications in megakaryopoiesis and hematopoietic stem cell replication not seen with other tested alpha granule proteins.


Assuntos
Grânulos Citoplasmáticos/metabolismo , Megacariócitos/metabolismo , Fator Plaquetário 4/metabolismo , Trombocitopenia/metabolismo , Trombopoese , Animais , Transporte Biológico , Células Cultivadas , Grânulos Citoplasmáticos/efeitos da radiação , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Megacariócitos/efeitos da radiação , Camundongos Knockout , Microscopia Confocal , Fator Plaquetário 4/deficiência , Fator Plaquetário 4/genética , Interferência de RNA , Receptores de LDL/genética , Receptores de LDL/metabolismo , Trombocitopenia/sangue , Trombocitopenia/genética , Fatores de Tempo , Transfecção , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
15.
Appl Environ Microbiol ; 80(21): 6694-703, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25149517

RESUMO

Biofilms are major causes of impairment of wound healing and patient morbidity. One of the most common and aggressive wound pathogens is Staphylococcus aureus, displaying a large repertoire of virulence factors and commonly reduced susceptibility to antibiotics, such as the spread of methicillin-resistant S. aureus (MRSA). Bacteriophages are obligate parasites of bacteria. They multiply intracellularly and lyse their bacterial host, releasing their progeny. We isolated a novel phage, DRA88, which has a broad host range among S. aureus bacteria. Morphologically, the phage belongs to the Myoviridae family and comprises a large double-stranded DNA (dsDNA) genome of 141,907 bp. DRA88 was mixed with phage K to produce a high-titer mixture that showed strong lytic activity against a wide range of S. aureus isolates, including representatives of the major international MRSA clones and coagulase-negative Staphylococcus. Its efficacy was assessed both in planktonic cultures and when treating established biofilms produced by three different biofilm-producing S. aureus isolates. A significant reduction of biofilm biomass over 48 h of treatment was recorded in all cases. The phage mixture may form the basis of an effective treatment for infections caused by S. aureus biofilms.


Assuntos
Biofilmes/crescimento & desenvolvimento , Myoviridae/crescimento & desenvolvimento , Fagos de Staphylococcus/crescimento & desenvolvimento , Staphylococcus aureus/fisiologia , Staphylococcus aureus/virologia , Bacteriólise , DNA Viral/química , DNA Viral/genética , Especificidade de Hospedeiro , Dados de Sequência Molecular , Myoviridae/fisiologia , Myoviridae/ultraestrutura , Análise de Sequência de DNA , Fagos de Staphylococcus/fisiologia , Fagos de Staphylococcus/ultraestrutura , Carga Viral
16.
Pulm Pharmacol Ther ; 26(6): 672-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23380438

RESUMO

PRM-151, recombinant human Pentraxin-2 (PTX-2) also referred to as serum amyloid P (SAP), is under development for treatment of fibrosis. A First-in-Human (FIH) trial was performed to assess the safety, tolerability, and pharmacokinetics of single ascending intravenous doses of PRM-151 administered to healthy subjects, using a randomized, blinded, placebo controlled study design. Each cohort included three healthy subjects (PRM-151:placebo; 2:1). SAP levels were assessed using a validated ELISA method, non-discriminating between endogenous and exogenous SAP. At a dose level of 10 mg/kg, at which a physiologic plasma level of SAP was reached, two additional healthy volunteers and three pulmonary fibrosis (PF) patients were enrolled enabling comparison of the pharmacokinetic SAP profile between healthy volunteers and PF patients. In addition, the percentage of fibrocytes (CD45+/Procollagen-1+ cells) in whole blood samples was assessed to demonstrate biological activity of PRM-151 in the target population. PRM-151 administration was generally well tolerated. In two pulmonary fibrosis patients non-specific, transient skin reactions (urticaria and erythema) were observed. PRM-151 administration resulted in a 6-to 13-fold increase in mean baseline plasma SAP levels at dose levels of 5, 10, and 20 mg/kg. The estimated t1/2 of PRM-151 in healthy volunteers was 30 h. Pharmacokinetic profiles were comparable between healthy volunteers and PF patients. PRM-151 administration resulted in a 30-50% decrease in fibrocyte numbers 24 h post-dose. This suggests that administration of PRM-151 may be associated with a reduction of fibrocytes in PF patients, a population for which current pharmacotherapeutic options are limited. The pharmacological action of PRM-151 should be confirmed in future research.


Assuntos
Proteínas de Homeodomínio/administração & dosagem , Fibrose Pulmonar/tratamento farmacológico , Componente Amiloide P Sérico/administração & dosagem , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Relação Dose-Resposta a Droga , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Feminino , Meia-Vida , Proteínas de Homeodomínio/efeitos adversos , Proteínas de Homeodomínio/farmacocinética , Humanos , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/fisiopatologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacocinética , Componente Amiloide P Sérico/efeitos adversos , Componente Amiloide P Sérico/farmacocinética , Adulto Jovem
17.
Pharmacol Biochem Behav ; 105: 34-40, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23380525

RESUMO

Recent research using the partially-baited radial arm maze with rats has shown that acute or single-session high-dose exposure to +/-3,4-methylenedioxymethaphemtamine (MDMA) impairs reference memory processes more so than working memory processes. The current study examined the effect that an initial binge exposure of MDMA had on the ability to learn this task and whether such exposure produced tolerance or sensitization to subsequent low dose acute MDMA exposure. Following either an initial binge dose (4×10mg/kg) of MDMA or saline, rats received regular weekly injections of either MDMA (4.0mg/kg) or saline during task acquisition training. Although eventually able to acquire the task at a level comparable to controls, initial binge MDMA exposure significantly impaired task acquisition. Binge-treated rats displayed evidence of a tolerance effect to subsequent acute injections of MDMA; although with continued training this tolerance effect was reduced. However, initial binge treatment also produced a sensitized response to subsequent acute MDMA exposure that manifested as a prolonged period of impairment up to 24h following administration. Consistent with the effects seen following other regimes of exposure to MDMA, the pattern of errors made was best described as an impairment to reference memory processes as opposed to working memory processes.


Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Aprendizagem/efeitos dos fármacos , Aprendizagem em Labirinto , N-Metil-3,4-Metilenodioxianfetamina/toxicidade , Animais , Masculino , Ratos , Ratos Sprague-Dawley
18.
J Nutr Health Aging ; 16(10): 888-90, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23208027

RESUMO

Circadian rhythmicity was repeatedly determined in a patient with Alzheimer's disease by measuring his core temperature with a rectal thermistor and motor activity by an ambulatory activity monitor. The first recording, performed 9 years after he was diagnosed with Alzheimer's disease, showed well organized 24 hr circadian rhythm of core body temperature. The second recording, made four months later, showed very poor fit of core body temperature to 24 hour rhythm, but excellent fit with 36 hour rhythm. The third recording, made two months later, showed again good fit of core body temperature with 24 hour cycle. The last recording, which was performed 5 months later, showed almost complete disappearance of circadian rhythm of body temperature. These changes probably reflect gradual lengthening of the circadian cycle that at one point became extremely lengthened before returning to the 24 hr cycle.


Assuntos
Doença de Alzheimer/fisiopatologia , Temperatura Corporal/fisiologia , Ritmo Circadiano/fisiologia , Atividade Motora/fisiologia , Idoso , Humanos , Masculino , Monitorização Fisiológica/métodos
19.
Int J Cancer ; 131(1): 106-16, 2012 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-21858807

RESUMO

In the Phase III PATRICIA study (NCT00122681), the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (Cervarix(®), GlaxoSmithKline Biologicals) was highly efficacious against HPV-16/18 infections and precancerous lesions in women HPV-16/18 deoxyribose nucleic acid (DNA) negative and seronegative at baseline. We present further data on vaccine efficacy (VE) against HPV-16/18 in the total vaccinated cohort including women who may have been exposed to HPV-16/18 infection before vaccination. In women with no evidence of current or previous HPV-16/18 infection (DNA negative and seronegative), VE was 90.3% (96.1% confidence interval: 87.3-92.6) against 6-month persistent infection (PI), 91.9% (84.6-96.2) against cervical intraepithelial neoplasia (CIN)1+ and 94.6% (86.3-98.4) against CIN2+ [97.7% (91.1-99.8) when using the HPV type assignment algorithm (TAA)]. In women HPV-16/18 DNA negative but with serological evidence of previous HPV-16/18 infection (seropositive), VE was 72.3% (53.0-84.5) against 6-month PI, 67.2% (10.9-89.9) against CIN1+, and 68.8% (-28.3-95.0) against CIN2+ [88.5% (10.8-99.8) when using TAA]. In women with no evidence of current HPV-16/18 infection (DNA negative), regardless of their baseline HPV-16/18 serological status, VE was 88.7% (85.7-91.1) against 6-month PI, 89.1% (81.6-94.0) against CIN1+ and 92.4% (84.0-97.0) against CIN2+ [97.0% (90.6-99.5) when using TAA]. In women who were DNA positive for one vaccine type, the vaccine was efficacious against the other vaccine type. The vaccine did not impact the outcome of HPV-16/18 infections present at the time of vaccination. Vaccination was generally well tolerated regardless of the woman's HPV-16/18 DNA or serological status at entry.


Assuntos
Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Adjuvantes Imunológicos , Adolescente , Adulto , Anticorpos Antivirais/sangue , Estudos de Coortes , DNA Viral/sangue , Feminino , Humanos , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/efeitos adversos , Resultado do Tratamento , Vacinação , Adulto Jovem , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/prevenção & controle
20.
Accid Anal Prev ; 43(6): 2015-2023, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21819830

RESUMO

Accurate gap-acceptance decisions require individuals to take into account both the distance to and the speed of an oncoming vehicle. The aim of the present studies was to develop an intervention that could successfully teach road users to focus on speed as well as distance. Across three studies, participants judged whether it was safe to cross the road or not when an oncoming vehicle was approaching from different distances and at different speeds. Study 1 trialed two techniques ("standard feedback" versus "three-look") aimed at improving gap judgments. Standard feedback involved telling participants what the actual speed of a car was after they had made an estimate, whereas the three-look technique required participants to make timed and controlled head movements when scanning the road environment. Only standard feedback increased the participants' mean gap-acceptance accuracy (assessed using both verbal and behavioral response measures). Study 2 also trialed two techniques, the standard feedback intervention used in Study 1, and a "two-response" intervention in which participants judged whether the oncoming vehicle was traveling at an atypical or normal speed. Study 2 found the two-response intervention to be more promising than the standard feedback procedure. Finally, Study 3 used video footage of oncoming vehicles to train younger (18-27 years) and older (60-80 years) adults and found the two-response intervention to be successful at improving gap-acceptance accuracies for both age groups. However, the intervention also resulted in more conservative gap judgments from participants in the older population independent of improvements in accuracy.


Assuntos
Condução de Veículo , Tomada de Decisões , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Conhecimento Psicológico de Resultados , Masculino , Pessoa de Meia-Idade , Análise e Desempenho de Tarefas , Adulto Jovem
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