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1.
Br J Anaesth ; 133(3): 500-507, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39025778

RESUMO

BACKGROUND: Identifying candidates for extracorporeal cardiopulmonary resuscitation (eCPR) is challenging, and novel predictive markers are urgently needed. Hyperfibrinolysis is linked to tissue hypoxia and is associated with poor outcomes in out-of-hospital cardiac arrest (OHCA). Rotational thromboelastometry (ROTEM) can detect or rule out hyperfibrinolysis, and could, therefore, provide decision support for initiation of eCPR. We explored early detection of hyperfibrinolysis in patients with refractory OHCA referred for eCPR. METHODS: We analysed ROTEM results and resuscitation parameters of 57 adult patients with ongoing OHCA who presented to our ICU for eCPR evaluation. RESULTS: Hyperfibrinolysis, defined as maximum lysis ≥15%, was present in 36 patients (63%) and was associated with higher serum lactate, lower arterial blood pH, and increased low-flow intervals. Of 42 patients who achieved return of circulation, 28 had a poor 30-day outcome. The incidence of hyperfibrinolysis was higher in the poor outcome group compared with patients with good outcomes (75% [21 of 28] vs 7.1% [1 of 14]; P<0.001). The ratio of EXTEM A5 to lactate concentration showed good predictive value in detecting hyperfibrinolysis (AUC of 0.89 [95% confidence interval 0.8-1]). CONCLUSIONS: Hyperfibrinolysis was common in patients with refractory cardiac arrest, and was associated with poor prognosis. The combination of high lactate with early clot firmness values, such as EXTEM A5, appears promising for early detection of hyperfibrinolysis. This finding could facilitate decisions to perform eCPR, particularly for patients with prolonged low-flow duration but lacking hyperfibrinolysis.


Assuntos
Reanimação Cardiopulmonar , Fibrinólise , Parada Cardíaca Extra-Hospitalar , Tromboelastografia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Tromboelastografia/métodos , Reanimação Cardiopulmonar/métodos , Prognóstico , Idoso , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/sangue , Parada Cardíaca Extra-Hospitalar/complicações , Fibrinólise/fisiologia , Oxigenação por Membrana Extracorpórea/métodos , Adulto , Ácido Láctico/sangue , Estudos Retrospectivos
2.
Clin Teach ; 21(2): e13671, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37840475

RESUMO

INTRODUCTION: Breaking bad news is one of the hardest tasks performed by doctors. The news can significantly impact on the patient's life; however, the process also generates stress for the doctor. The aim of this study was to explore the lived experiences of breaking bad news for obstetrics trainees in Ireland. METHODS: A qualitative study using interpretative phenomenological analysis (IPA) was performed to capture the experience of breaking bad news for the trainees. Semi-structured interviews were conducted with trainees over Zoom. The transcripts were analysed in line with the IPA framework with the assistance of NVivo software. RESULTS: Seven trainees were interviewed, five at Basic Specialist Training (BST) level and two at Higher Specialist Training (HST) level. Four superordinate themes were identified from the analysis: "the reality of working in obstetrics," "the role of the doctor," "development of communication skills" and "the importance of the patient experience." The trainees described breaking bad news in a variety of clinical contexts. This task could be emotionally draining; however, only two trainees mentioned ways of coping with this. Their formal training was limited with the majority of learning occurring "on the job." CONCLUSIONS: This study provides an insight into factors that influence trainees experiences of breaking bad news. The results complemented existing literature and raised questions about how to better support trainees through increased training and psychological support.


Assuntos
Médicos , Revelação da Verdade , Humanos , Médicos/psicologia , Escolaridade , Pesquisa Qualitativa , Comunicação , Relações Médico-Paciente
3.
Eur J Endocrinol ; 189(6): 619-626, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38035766

RESUMO

OBJECTIVE: The effect of oral glucose-induced release of gastrointestinal hormones on satiety and appetite independently of prevailing plasma glucose excursions is unknown. The objective is to investigate the effect of oral glucose on appetite and satiety sensations as compared to isoglycemic IV glucose infusion (IIGI) in healthy volunteers. DESIGN: A crossover study involving two study days for each participant. PARTICIPANTS: Nineteen healthy participants (6 women, mean age 55.1 [SD 14.2] years; mean body mass index 26.7 [SD 2.2] kg/m2). INTERVENTIONS: Each participant underwent a 3-h 50-g oral glucose tolerance test (OGTT) and, on a subsequent study day, an IIGI mimicking the glucose excursions from the OGTT. On both study days, appetite and satiety were indicated regularly on visual analog scale (VAS), and blood was drawn regularly for measurement of pancreatic and gut hormones. PRIMARY OUTCOMES: Difference in appetite and satiety sensations during OGTT and IIGI. RESULTS: Circulating concentrations of glucose-dependent insulinotropic polypeptide (P < .0001), glucagon-like peptide 1 (P < .0001), insulin (P < .0001), C-peptide (P < .0001), and neurotensin (P = .003) increased significantly during the OGTT as compared to the IIGI, whereas glucagon responses were similarly suppressed (P = .991). Visual analog scale-assessed ratings of hunger, satiety, fullness, thirst, well-being, and nausea, respectively, were similar during OGTT and IIGI whether assessed as mean 0-3-h values or area under the curves. For both groups, a similar, slow increase in appetite and decrease in satiation were observed. Area under the curve, for prospective food consumption (P = .049) and overall appetite score (P = .044) were slightly lower during OGTT compared to IIGI, whereas mean 0-3-h values were statistically similar for prospective food consumption (P = .053) and overall appetite score (P = .063). CONCLUSIONS: Despite eliciting robust responses of appetite-reducing and/or satiety-promoting gut hormones, we found that oral glucose administration has little or no effect on appetite and satiety as compared to an IIGI, not affecting the release of appetite-modulating hormones. TRIAL REGISTRY NO: ClinicalTrials.gov: NCT01492283 and NCT06064084.


Assuntos
Hormônios Gastrointestinais , Glucose , Humanos , Feminino , Pessoa de Meia-Idade , Apetite/fisiologia , Glicemia , Estudos Cross-Over , Glucagon , Insulina , Saciação , Sensação
4.
Data Brief ; 48: 109181, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37180879

RESUMO

A dataset describing the occurrence of wild bees and their interaction with forage plants along livestock grazing gradient is critical in understanding bee-plant interaction networks and in developing conservation plans to ensure ecosystem services in human-modified landscapes. Despite this need, bee-plant datasets are scarce in Africa, and Tanzania is no exception. Therefore, in this article, we present a dataset of wild bee species richness, occurrence, and distribution collected across sites with different levels of livestock grazing intensity and forage resources thereby. The data presented in this paper supports a research article by Lasway et al., 2022 describing the effects of grazing intensity on East African bee assemblages. The paper presents primary data on bee species, collection method, date of collection, bee family, identifier, plant forage resource, forage plant life form, forage plant family, location (GPS coordinates), grazing intensity category, mean annual temperature (°C), and elevation (m asl). The data were collected intermittently between August 2018 and March 2020 from 24 study sites distributed along three levels of livestock grazing intensity with eight replicates for each: low, moderate, and high livestock grazing intensity. In each study site, two 50 × 50 m study plots were set from which bees and floral resources were sampled and quantified. The two plots were placed in a way to capture the overall structural heterogeneity of the respective habitat by placing the two plots in contrasting microhabitats where possible. For example, in moderately livestock-grazed habitats, plots were placed on sites with and without tree or shrub cover to ensure representativeness. This paper presents a dataset comprising 2,691 bee individuals from 183 species representing 55 genera of the five bee families: Halictidae (74), Apidae (63), Megachilidae (40), Andrenidae (5), and Colletidae (1). In addition, the dataset comprises 112 species of flowering plants that were identified as potential forage resources for bees. This paper supplements rare but critical data on bee pollinators in Northern Tanzania and advances our knowledge of the potential drivers of bee-pollinator whose populations diversity are declining globally. The dataset will also promote collaborations among researchers who would wish to combine and extend their data for further analysis to gain a broader understanding of the phenomenon on a larger spatial scale.

5.
Diabetes Obes Metab ; 25(6): 1566-1575, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36752677

RESUMO

AIM: To investigate changes in cardiac repolarization abnormalities (heart rate-corrected QT [QTc ] [primary endpoint], T-wave abnormalities) and heart-rate variability measures in people with type 1 diabetes during insulin-induced hypoglycaemia followed by recovery hyperglycaemia versus euglycaemia. METHODS: In a randomized crossover study, 24 individuals with type 1 diabetes underwent two experimental clamps with three steady-state phases during electrocardiographic monitoring: (1) a 45-minute euglycaemic phase (5-8 mmol/L), (2) a 60-minute insulin-induced hypoglycaemic phase (2.5 mmol/L), and (3) 60-minute recovery in either hyperglycaemia (20 mmol/L) or euglycaemia (5-8 mmol/L). RESULTS: All measured markers of arrhythmic risk indicated increased risk during hypoglycaemia. These findings were accompanied by a decrease in vagal tone during both hyperglycaemia and euglycaemia clamps. Compared with baseline, the QTc interval increased during hypoglycaemia, and 63% of the participants exhibited a peak QTc of more than 500 ms. The prolonged QTc interval was sustained during both recovery phases with no difference between recovery hyperglycaemia versus euglycaemia. During recovery, no change from baseline was observed in heart-rate variability measures. CONCLUSIONS: In people with type 1 diabetes, insulin-induced hypoglycaemia prolongs cardiac repolarization, which is sustained during a 60-minute recovery period independently of recovery to hyperglycaemia or euglycaemia. Thus, vulnerability to serious cardiac arrhythmias and sudden cardiac death may extend beyond a hypoglycaemic event, regardless of hyperglycaemic or euglycaemic recovery.


Assuntos
Diabetes Mellitus Tipo 1 , Hiperglicemia , Hipoglicemia , Síndrome do QT Longo , Humanos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hiperglicemia/induzido quimicamente , Frequência Cardíaca , Estudos Cross-Over , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemia/complicações , Arritmias Cardíacas/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina Regular Humana/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/complicações
7.
Diabetes Obes Metab ; 24(10): 2027-2037, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35670658

RESUMO

AIM: To investigate echocardiographic changes during acute hypoglycaemia followed by recovery to hyperglycaemia or euglycaemia in patients with type 1 diabetes. MATERIALS AND METHODS: In a randomized crossover study, 24 patients with type 1 diabetes took part in two experimental study days, consisting of a hyperinsulinaemic-euglycaemic phase (5.0-8.0 mmol/L) for 45 minutes followed by a hyperinsulinemic-hypoglycaemic phase (2.5 mmol/L) for 60 minutes, and a recovery phase in either hyperglycaemia (20 mmol/L) or euglycaemia (5.0-8.0 mmol/L) for 60 minutes. Cardiac function was evaluated with echocardiography during each phase. RESULTS: Acute hypoglycaemia increased all markers of left ventricular (LV) systolic function, including LV ejection fraction (LVEF), global longitudinal strain (GLS), GLS rate and peak systolic velocity of mitral annular longitudinal movement (s'; P < 0.001 for all). During the recovery phases, all markers of LV systolic function were increased during hyperglycaemia (P < 0.01 for all), and LVEF and GLS remained increased during euglycaemia (P = 0.0116 and P = 0.0092, respectively). The increment in LVEF during the recovery phase was greater during hyperglycaemia than euglycaemia (P = 0.0046). CONCLUSIONS: Hypoglycaemia, recent hypoglycaemia, and overcorrection of hypoglycaemia to rebound hyperglycaemia increased LV systolic function in type 1 diabetes and may imply consideration of plasma glucose when evaluating LV function in patients with type 1 diabetes. An increase in LV systolic function may cause increased strain on the heart and partly explain the link between hypoglycaemia, high glycaemic variability and cardiovascular disease.


Assuntos
Diabetes Mellitus Tipo 1 , Hiperglicemia , Hipoglicemia , Disfunção Ventricular Esquerda , Biomarcadores , Estudos Cross-Over , Diabetes Mellitus Tipo 1/complicações , Humanos , Hiperglicemia/complicações , Hipoglicemia/complicações , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia
8.
Artigo em Inglês | MEDLINE | ID: mdl-35633593

RESUMO

Cardiovascular disease is the leading cause of mortality in patients with renal failure. Red blood cells (RBCs) are potential reservoirs for epoxy fatty acids (oxylipins) that regulate cardiovascular function. Hemoglobin exhibits pseudo-lipoxygenase activity in vitro. We previously assessed the impact of single hemodialysis (HD) treatment on RBC epoxy fatty acids status in circulating arterial blood and found that eicosanoids in oxygenated RBCs could be particularly vulnerable in chronic kidney disease and hemodialysis. The purpose of the present study was to evaluate the differences of RBC epoxy fatty acids profiles in arterial and venous blood in vivo (AV differences) from patients treated by HD treatment. We collected arterial and venous blood samples in upper limbs from 12 end-stage renal disease (ESRD) patients (age 72±12 years) before and after HD treatment. We measured oxylipins derived from cytochrome P450 (CYP) monooxygenase and lipoxygenase (LOX)/CYP ω/(ω-1)-hydroxylase pathways in RBCs by LC-MS/MS tandem mass spectrometry. Our data demonstrate arteriovenous differences in LOX pathway metabolites in RBCs after dialysis, including numerous hydroxyeicosatetraenoic acids (HETEs), hydroxydocosahexaenoic acids (HDHAs) and hydroxyeicosapentaenoic acids (HEPEs). We detected more pronounced changes in free metabolites in RBCs after HD, as compared with the total RBC compartment. Hemodialysis treatment did not affect the majority of CYP and CYP ω/(ω-1)-hydroxylase products in RBCs. Our data indicate that erythro-metabolites of the LOX pathway are influenced by renal-replacement therapies, which could have deleterious effects in the circulation.


Assuntos
Ácidos Graxos Ômega-3 , Ácidos Graxos , Idoso , Idoso de 80 Anos ou mais , Biotransformação , Cromatografia Líquida , Sistema Enzimático do Citocromo P-450/metabolismo , Eritrócitos/metabolismo , Ácidos Graxos/metabolismo , Humanos , Lipoxigenase/metabolismo , Pessoa de Meia-Idade , Oxilipinas , Diálise Renal , Espectrometria de Massas em Tandem
9.
Metabolites ; 12(1)2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-35050156

RESUMO

Factors causing the increased cardiovascular morbidity and mortality in hemodialysis (HD) patients are largely unknown. Oxylipins are a superclass of lipid mediators with potent bioactivities produced from oxygenation of polyunsaturated fatty acids. We previously assessed the impact of HD on oxylipins in arterial blood plasma and found that HD increases several oxylipins. To study the phenomenon further, we now evaluated the differences in arterial and venous blood oxylipins from patients undergoing HD. We collected arterial and venous blood samples in upper extremities from 12 end-stage renal disease (ESRD) patients before and after HD and measured oxylipins in plasma by LC-MS/MS tandem mass spectrometry. Comparison between cytochrome P450 (CYP), lipoxygenase (LOX), and LOX/CYP ω/(ω-1)-hydroxylase metabolites levels from arterial and venous blood showed no arteriovenous differences before HD but revealed arteriovenous differences in several CYP metabolites immediately after HD. These changes were explained by metabolites in the venous blood stream of the upper limb. Decreased soluble epoxide hydrolase (sEH) activity contributed to the release and accumulation of the CYP metabolites. However, HD did not affect arteriovenous differences of the majority of LOX and LOX/CYP ω/(ω-1)-hydroxylase metabolites. The HD treatment itself causes changes in CYP epoxy metabolites that could have deleterious effects in the circulation.

10.
Biodivers Data J ; 9: e68190, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497474

RESUMO

BACKGROUND: Bees (Hymenoptera: Apoidea: Anthophila) are the most important group of pollinators with about 20,507 known species worldwide. Despite the critical role of bees in providing pollination services, studies aiming at understanding which species are present across disturbance gradients are scarce. Limited taxononomic information for the existing and unidentified bee species in Tanzania make their conservation haphazard. Here, we present a dataset of bee species records obtained from a survey in nothern Tanzania i.e. Kilimanjaro, Arusha and Manyara regions. Our findings serve as baseline data necessary for understanding the diversity and distribution of bees in the northern parts of the country, which is a critical step in devising robust conservation and monitoring strategies for their populations. NEW INFORMATION: In this paper, we present information on 45 bee species belonging to 20 genera and four families sampled using a combination of sweep-netting and pan trap methods. Most species (27, ~ 60%) belong to the family Halictidae followed by 16 species (35.5%) from the family Apidae. Megachilidae and Andrenidae were the least represented, each with only one species (2.2%). Additional species of Apidae and Megachilidae sampled during this survey are not yet published on Global Biodiversity Information Facility (GBIF), once they will be available on GBIF, they will be published in a subsequent paper. From a total of 953 occurrences, highest numbers were recorded in Kilimanjaro Region (n = 511), followed by Arusha (n = 410) and Manyara (n = 32), but this pattern reflects the sampling efforts of the research project rather than real bias in the distributions of bee species in northern Tanzania.

11.
J Surg Res ; 268: 411-418, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34416413

RESUMO

BACKGROUND: A novel Palladium-103 low-dose rate (LDR) brachytherapy device was developed to provide dose-escalation to the tumor bed after resection while shielding adjacent tissues. This multicenter report describes the initial experience with this device in patients with retroperitoneal sarcoma (RPS). MATERIALS AND METHODS: Patients with recurrent RPS, prior radiotherapy, and/or concern for positive margins were considered. An LDR brachytherapy dose of 20-60 Gy was administered, corresponding to biologically effective dose values of 15-53 Gy and equivalent dose values of 12-43 Gy. RESULTS: Six patients underwent implantation at four institutions. Of these, five had recurrent disease in the retroperitoneum or pelvic sidewall, one had untreated locally advanced leiomyosarcoma, two had prior external beam radiation therapy at the time of initial diagnosis, and four received neoadjuvant external beam radiation therapy plus brachytherapy. The device was easily implanted and conformed to the treatment area. Median follow-up was 16 mo; radiation was delivered to the at-risk margin with minimal irradiation of adjacent structures. No local recurrences at the site of implantation, device migration, or radiation-related toxicities were observed. CONCLUSIONS: The novel LDR directional brachytherapy device successfully delivered a targeted dose escalation to treat RPS high-risk margins. Lack of radiation-related toxicity demonstrates its safety.


Assuntos
Braquiterapia , Neoplasias Retroperitoneais , Sarcoma , Braquiterapia/efeitos adversos , Humanos , Recidiva Local de Neoplasia/cirurgia , Dosagem Radioterapêutica , Neoplasias Retroperitoneais/radioterapia , Neoplasias Retroperitoneais/cirurgia , Estudos Retrospectivos , Sarcoma/radioterapia , Sarcoma/cirurgia
12.
J Neurochem ; 159(3): 525-542, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34379806

RESUMO

Sepsis-associated encephalopathy (SAE) represents diverse cerebral dysfunctions in response to pathogen-induced systemic inflammation. Peripheral exposure to lipopolysaccharide (LPS), a component of the gram-negative bacterial cell wall, has been extensively used to model systemic inflammation. Our previous studies suggested that LPS led to hippocampal neuron death and synaptic destruction in vivo. However, the underlying roles of activated microglia in these neuronal changes remained unclear. Here, LPS from two different bacterial strains (Salmonella enterica or E. coli) were compared and injected in 14- to 16-month-old mice and evaluated for neuroinflammation and neuronal integrity in the hippocampus at 7 or 63 days post-injection (dpi). LPS injection resulted in persistent neuroinflammation lasting for seven days and a subsequent normalisation by 63 dpi. Of note, increases in proinflammatory cytokines, microglial morphology and microglial mean lysosome volume were more pronounced after E. coli LPS injection than Salmonella LPS at 7 dpi. While inhibitory synaptic puncta density remained normal, excitatory synaptic puncta were locally reduced in the CA3 region of the hippocampus at 63 dpi. Finally, we provide evidence that excitatory synapses coated with complement factor 3 (C3) decreased between 7 dpi and 63 dpi. Although we did not find an increase of synaptic pruning by microglia, it is plausible that microglia recognised and eliminated these C3-tagged synapses between the two time points of investigation. Since a region-specific decline of CA3 synapses has previously been reported during normal ageing, we postulate that systemic inflammation may have accelerated or worsened the CA3 synaptic changes in the ageing brain.


Assuntos
Envelhecimento/patologia , Região CA3 Hipocampal/patologia , Inflamação/patologia , Sinapses/patologia , Animais , Feminino , Imuno-Histoquímica , Lipopolissacarídeos , Camundongos , Camundongos Endogâmicos C57BL , Microglia/patologia , Salmonella , Sepse/patologia , Sinaptossomos/patologia
13.
PLoS One ; 15(1): e0228017, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32004331

RESUMO

Financial barriers are a major obstacle to accessing maternal health care services in low-resource settings. In Madagascar, less than half of live births are attended by skilled health staff. Although mobile money-based savings and payment systems are often used to pay for a variety of services, including health care, data on the implications of a dedicated mobile money wallet restricted to health-related spending during pregnancy-a mobile health wallet (MHW)-are not well understood. In cooperation with the Madagascan Ministry of Health, this study aims to elicit the perceptions, experiences, and recommendations of key stakeholders in relation to a MHW amid a pilot study in 31 state-funded health care facilities. We conducted a two-stage qualitative study using semi-structured in-depth interviews with stakeholders (N = 21) representing the following groups: community representatives, health care providers, health officials and representatives from phone provider companies. Interviews were conducted in Atsimondrano and Renivohitra districts, between November and December of 2017. Data was coded thematically using inductive and deductive approaches, and found to align with a social ecological model. Key facilitators for successful implementation of the MHW, include (i) close collaboration with existing communal structures and (ii) creation of an incentive scheme to reward pregnant women to save. Key barriers to the application of the MHW in the study zone include (i) disruption of informal benefits for health care providers related to the current cash-based payment system, (ii) low mobile phone ownership, (iii) illiteracy among the target population, and (iv) failure of the MHW to overcome essential access barriers towards institutional health care services such as fear of unpredictable expenses. The MHW was perceived as a potential solution to reduce disparities in access to maternal health care. To ensure success of the MHW, direct demand-side and provider-side financial incentives merit consideration.


Assuntos
Telefone Celular , Acessibilidade aos Serviços de Saúde , Serviços de Saúde Materna , Telemedicina , Adulto , Telefone Celular/economia , Telefone Celular/instrumentação , Feminino , Pessoal de Saúde , Necessidades e Demandas de Serviços de Saúde , Humanos , Madagáscar , Motivação , Projetos Piloto , Gravidez , Gestantes , Pesquisa Qualitativa , Qualidade da Assistência à Saúde , Telemedicina/economia , Telemedicina/instrumentação
14.
Brain Sci ; 9(10)2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31652564

RESUMO

Although early reperfusion after stroke salvages the still-viable ischemic tissue, peri-infarct selective neuronal loss (SNL) can cause sensorimotor deficits (SMD). We designed a longitudinal protocol to assess the effects of cytoprotectants on SMD, microglial activation (MA) and SNL, and specifically tested whether the KCa3.1-blocker TRAM-34 would prevent SNL. Spontaneously hypertensive rats underwent 15 min middle-cerebral artery occlusion and were randomized into control or treatment group, which received TRAM-34 intraperitoneally for 4 weeks starting 12 h after reperfusion. SMD was assessed longitudinally using the sticky-label test. MA was quantified at day 14 using in vivo [11C]-PK111195 positron emission tomography (PET), and again across the same regions-of-interest template by immunofluorescence together with SNL at day 28. SMD recovered significantly faster in the treated group (p = 0.004). On PET, MA was present in 5/6 rats in each group, with no significant between-group difference. On immunofluorescence, both SNL and MA were present in 5/6 control rats and 4/6 TRAM-34 rats, with a non-significantly lower degree of MA but a significantly (p = 0.009) lower degree of SNL in the treated group. These findings document the utility of our longitudinal protocol and suggest that TRAM-34 reduces SNL and hastens behavioural recovery without marked MA blocking at the assessed time-points.

15.
ALTEX ; 36(4): 555-571, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31026040

RESUMO

Ideally, humane endpoints allow for early termination of experiments by minimizing an animal's discomfort, distress and pain, while ensuring that scientific objectives are reached. Yet, lack of commonly agreed methodology and heterogeneity of cut-off values published in the literature remain a challenge to the accurate determination and application of humane endpoints. With the aim to synthesize and appraise existing humane endpoint definitions for commonly used physiological parameters, we conducted a systematic review of mouse studies of acute and chronic disease models, which used body weight, temperature and/or sickness scores for endpoint definition. In the second part of the study, we used previously published and unpublished data on weight, temperature and sickness scores from mouse models of sepsis and stroke and applied machine learning algorithms to assess the usefulness of this method for parameter selection and endpoint definition across models. Studies were searched for in two electronic databases (MEDLINE/Pubmed and Embase). Out of 110 retrieved full-text manuscripts, 34 studies were included. We found large intra- and inter-model variance in humane endpoint determination and application due to varying animal models, lack of standardized experimental protocols and heterogeneity of performance metrics (part 1). Machine learning models trained with physiological data and sickness severity score or modified DeSimoni neuroscore identified animals with a high risk of death at an early time point in both mouse models of stroke (male: 93.2% at 72h post-treatment; female: 93.0% at 48h post-treatment) and sepsis (96.2% at 24h post-treatment), thus demonstrating generalizability in endpoint determination across models (part 2).


Assuntos
Bem-Estar do Animal , Modelos Animais de Doenças , Aprendizado de Máquina Supervisionado , Revisões Sistemáticas como Assunto , Animais , Feminino , Masculino , Camundongos , Temperatura Corporal , Peso Corporal , Revisão Ética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Distribuição Aleatória , Sepse/fisiopatologia , Índice de Gravidade de Doença , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo
17.
Phys Med Biol ; 63(2): 025016, 2018 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-29243663

RESUMO

By collimating the photons scattered when a megavoltage therapy beam interacts with the patient, a Compton-scatter image may be formed without the delivery of an extra dose. To characterize and assess the potential of the technique, an analytical model for simulating scatter images was developed and validated against Monte Carlo (MC). For three phantoms, the scatter images collected during irradiation with a 6 MV flattening-filter-free therapy beam were simulated. Images, profiles, and spectra were compared for different phantoms and different irradiation angles. The proposed analytical method simulates accurate scatter images up to 1000 times faster than MC. Minor differences between MC and analytical simulated images are attributed to limitations in the isotropic superposition/convolution algorithm used to analytically model multiple-order scattering. For a detector placed at 90° relative to the treatment beam, the simulated scattered photon energy spectrum peaks at 140-220 keV, and 40-50% of the photons are the result of multiple scattering. The high energy photons originate at the beam entrance. Increasing the angle between source and detector increases the average energy of the collected photons and decreases the relative contribution of multiple scattered photons. Multiple scattered photons cause blurring in the image. For an ideal 5 mm diameter pinhole collimator placed 18.5 cm from the isocenter, 10 cGy of deposited dose (2 Hz imaging rate for 1200 MU min-1 treatment delivery) is expected to generate an average 1000 photons per mm2 at the detector. For the considered lung tumor CT phantom, the contrast is high enough to clearly identify the lung tumor in the scatter image. Increasing the treatment beam size perpendicular to the detector plane decreases the contrast, although the scatter subject contrast is expected to be greater than the megavoltage transmission image contrast. With the analytical method, real-time tumor tracking may be possible through comparison of simulated and acquired patient images.


Assuntos
Algoritmos , Neoplasias Pulmonares/radioterapia , Método de Monte Carlo , Imagens de Fantasmas , Fótons , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador , Espalhamento de Radiação
18.
Phys Med Biol ; 63(2): 025018, 2018 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-29176057

RESUMO

Acoustic-based proton range verification (protoacoustics) is a potential in vivo technique for determining the Bragg peak position. Previous measurements and simulations have been restricted to homogeneous water tanks. Here, a CT-based simulation method is proposed and applied to a liver and prostate case to model the effects of tissue heterogeneity on the protoacoustic amplitude and time-of-flight range verification accuracy. For the liver case, posterior irradiation with a single proton pencil beam was simulated for detectors placed on the skin. In the prostate case, a transrectal probe measured the protoacoustic pressure generated by irradiation with five separate anterior proton beams. After calculating the proton beam dose deposition, each CT voxel's material properties were mapped based on Hounsfield Unit values, and thermoacoustically-generated acoustic wave propagation was simulated with the k-Wave MATLAB toolbox. By comparing the simulation results for the original liver CT to homogenized variants, the effects of heterogeneity were assessed. For the liver case, 1.4 cGy of dose at the Bragg peak generated 50 mPa of pressure (13 cm distal), a 2× lower amplitude than simulated in a homogeneous water tank. Protoacoustic triangulation of the Bragg peak based on multiple detector measurements resulted in 0.4 mm accuracy for a δ-function proton pulse irradiation of the liver. For the prostate case, higher amplitudes are simulated (92-1004 mPa) for closer detectors (<8 cm). For four of the prostate beams, the protoacoustic range triangulation was accurate to ⩽1.6 mm (δ-function proton pulse). Based on the results, application of protoacoustic range verification to heterogeneous tissue will result in decreased signal amplitudes relative to homogeneous water tank measurements, but accurate range verification is still expected to be possible.


Assuntos
Acústica , Simulação por Computador , Neoplasias Hepáticas/radioterapia , Imagens de Fantasmas , Neoplasias da Próstata/radioterapia , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Método de Monte Carlo , Neoplasias da Próstata/diagnóstico por imagem , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios X/métodos
19.
J Appl Clin Med Phys ; 19(2): 48-53, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29105949

RESUMO

The sparing of the parotid glands in the treatment of head and neck cancers is of clinical relevance as high doses to the salivary glands may result in xerostomia. Xerostomia is a major cause of decreased quality of life for head and neck patients. This paper explores the relationship between the overlap of the target volumes and their expansions with the parotid glands for helical delivery plans and their ability to be spared. Various overlapping volumes were examined, and an overlap with a high statistical relevance was found. A model that predicts exceeding tolerance parotid mean dose based on its fractional overlapping volume with PTVs was developed. A fractional overlapping volume of 0.083 between the parotid gland and the high dose PTV plus 5 mm expansion - was determined to be the threshold value to predict parotid Dmean  > 26 Gy for parotids that overlap with the high dose PTV plus 5 mm expansion. If the parotid gland only overlaps with the intermediate dose target (and/or low dose target) and the overlapping volume of the parotid gland and the intermediate dose target is less than 25%, the parotid mean dose is likely less than 26 Gy. If the parotid overlaps with the low dose target only then the mean dose to the parotid is likely to be less than 26 Gy. This finding will prove as a very useful guide for the physicians and planners involved in the planning process to know prior whether the parotid glands will be able to be spared with the current set of target volumes or if revisions are necessary. This work will serve as a helpful guide in the planning process of head and neck target cases.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Tratamentos com Preservação do Órgão/normas , Órgãos em Risco/efeitos da radiação , Glândula Parótida/efeitos da radiação , Radioterapia Conformacional/efeitos adversos , Xerostomia/prevenção & controle , Humanos , Prognóstico , Qualidade de Vida , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos
20.
Vet World ; 10(2): 181-186, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28344401

RESUMO

BACKGROUND: Artificial insemination (AI) is a reproductive biotechnology that may be influenced by several factors, including the profile of the technicians and the practices used. Assessing technician's profile and their AI practices can be significant in improving AI success rate. AIM: This study aimed to know the profile and current practices used by AI technicians (AITs), to determine the success rates of AI in water buffaloes in Leyte, Samar, and Biliran from 2011 to 2015, and to evaluate the possible association between the parameters investigated. MATERIALS AND METHODS: A total of 50 AITs from Leyte, Samar and Biliran, Philippines, were interviewed using a fixed questionnaire about their profile and employed AI practices, and 20,455 AI-related records of the Philippine Carabao Center (PCC) at Visayas State University (VSU), Baybay City, Leyte, were screened and analyzed. AI success rates were determined by retrospective analysis of the gathered data. Statistical analysis was performed between the technician profile and practices and the AI success rates. RESULTS: Results revealed that most of the technicians were male, around 31-40 years old, married, college graduates, working under local government units, had other sources of income, and with 1-5 years of continuous AI practice averaging 51-100 inseminations per year. Most of them attended only one basic training seminar, which was conducted more than 3 years ago in PCC in VSU. AI success rates were recorded highest in 2011 and lowest in 2015. Statistical analyses showed that some technician profile parameters (civil status, average AI per year, and the training center) and several practices (checking of soft cervix, rectal palpation, thawing temperature method, straw cutting method, and semen deposition) might have an influence on the success of AI. CONCLUSION: This study documents the first report on AIT's profile and their employed AI practices and the AI success rates in Leyte, Samar, and Biliran, Philippines. Selected profile parameters and AI practices may influence AI success rates. AITs should perform more AI services and revisit the employed practices.

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