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1.
Brain ; 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38038360

RESUMO

AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs) mediate fast excitatory neurotransmission in the brain. AMPARs form by homo- or heteromeric assembly of subunits encoded by the GRIA1-GRIA4 genes, of which only GRIA3 is X-chromosomal. Increasing numbers of GRIA3 missense variants are reported in patients with neurodevelopmental disorders (NDD), but only a few have been examined functionally. Here, we evaluated the impact on AMPAR function of one frameshift and 43 rare missense GRIA3 variants identified in patients with NDD by electrophysiological assays. Thirty-one variants alter receptor function and show loss-of-function (LoF) or gain-of-function (GoF) properties, whereas 13 appeared neutral. We collected detailed clinical data from 25 patients (from 23 families) harbouring 17 of these variants. All patients had global developmental impairment, mostly moderate (9/25) or severe (12/25). Twelve patients had seizures, including focal motor (6/12), unknown onset motor (4/12), focal impaired awareness (1/12), (atypical) absence (2/12), myoclonic (5/12), and generalized tonic-clonic (1/12) or atonic (1/12) seizures. The epilepsy syndrome was classified as developmental and epileptic encephalopathy in eight patients, developmental encephalopathy without seizures in 13 patients, and intellectual disability with epilepsy in four patients. Limb muscular hypotonia was reported in 13/25, and hypertonia in 10/25. Movement disorders were reported in 14/25, with hyperekplexia or non-epileptic erratic myoclonus being the most prevalent feature (8/25). Correlating receptor functional phenotype with clinical features revealed clinical features for GRIA3-associated NDDs and distinct NDD phenotypes for LoF and GoF variants. GoF variants were associated with more severe outcomes: patients were younger at the time of seizure onset (median age one month), hypertonic, and more often had movement disorders, including hyperekplexia. Patients with LoF variants were older at the time of seizure onset (median age 16 months), hypotonic, and had sleeping disturbances. LoF and GoF variants were disease-causing in both sexes but affected males often carried de novo or hemizygous LoF variants inherited from healthy mothers, whereas all but one affected females had de novo heterozygous GoF variants.

2.
Eur J Clin Microbiol Infect Dis ; 41(8): 1133-1138, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35790590

RESUMO

Infections with hypervirulent Klebsiella pneumoniae (hvKp) commonly presents with primary liver infection, bacteremia, and metastatic abscesses. Here, we present 2 cases of severe community-acquired pulmonary infections by hvKp in patients in the Netherlands without recent travel history. Both bacterial isolates are closely related to an archetype ST23 hvKp reference isolate. Based on these findings, surveillance programs on hvKp may consider to include isolates from community-acquired pneumonia by K. pneumoniae.


Assuntos
Infecções Comunitárias Adquiridas , Infecções por Klebsiella , Pneumonia , Infecções Comunitárias Adquiridas/microbiologia , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae , Países Baixos , Virulência
3.
Mol Pharmacol ; 96(6): 835-850, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31582576

RESUMO

The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) constitute a subclass of the ionotropic glutamate receptor superfamily, which functions as glutamate-gated cation channels to mediate the majority of excitatory neurotransmission in the central nervous system. AMPARs are therapeutic targets in a range of brain disorders associated with abnormal glutamate hyperactivity. Multiple classes of AMPAR inhibitors have been developed during the past decades, including competitive antagonists, ion channel blockers, and negative allosteric modulators (NAMs). At present, the NAM is the only class of AMPAR ligands that have been developed into safe and useful drugs in humans in the form of perampanel (Fycompa), which was recently approved for treatment of epilepsy. Compared with the detailed understanding of other AMPAR ligand classes, surprisingly little information has been available regarding the molecular mechanism of perampanel and other classes of NAMs at AMPARs; including the location and structure of NAM binding pockets in the receptor complex. However, structures of the AMPAR GluA2 in complex with NAMs were recently reported that unambiguously identified the NAM binding sites. In parallel with this work, our aim with the present study was to identify specific residues involved in the formation of the NAM binding site for three prototypical AMPAR NAMs. Hence, we have performed a mutational analysis of the AMPAR region that links the four extracellular ligand-binding domains to the central ion channel in the transmembrane domain region. Furthermore, we perform computational ligand docking of the NAMs into structural models of the homomeric GluA2 receptor and optimize side chain conformations around the NAMs to model how NAMs bind in this specific site. The new insights provide potentially valuable input for structure-based drug design of new NAMs. SIGNIFICANCE STATEMENT: The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are glutamate-gated ion channels that mediate the majority of excitatory neurotransmission in the brain. Negative allosteric modulators of AMPA receptors are considered to have significant therapeutic potential in diseases linked to glutamate hyperactivity. The present work employs mutational analysis and molecular modeling of the binding site for prototypical NAMs to provide new molecular insight into how NAMs interact with the AMPA receptor, which is of potential use for future design of new types of NAMs.


Assuntos
Mutação/genética , Receptores de Glutamato/química , Receptores de Glutamato/genética , Regulação Alostérica/efeitos dos fármacos , Regulação Alostérica/fisiologia , Animais , Sítios de Ligação/efeitos dos fármacos , Sítios de Ligação/fisiologia , Cristalografia por Raios X , Feminino , Células HEK293 , Humanos , Nitrilas , Estrutura Secundária de Proteína , Piridonas/farmacologia , Receptores de Glutamato/metabolismo , Xenopus laevis
4.
Crit Care ; 23(1): 219, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31200780

RESUMO

BACKGROUND: The objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe. METHODS: A multinational, multicenter, retrospective study was conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU). RESULTS: During the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio [OR] 1.04 per year, 95% CI 1.02-1.06, p < 0.001), severe hepatic failure (OR 3.25, 95% 1.31-8.08, p 0.011), SOFA score at the onset of IC (OR 1.11 per point, 95% CI 1.04-1.17, p 0.001), and septic shock (OR 2.12, 95% CI 1.24-3.63, p 0.006) were associated with increased 30-day mortality in a secondary, exploratory analysis. CONCLUSIONS: The cumulative incidence of IC in 23 European ICUs was 7.07 episodes per 1000 ICU admissions. Future in-depth analyses will allow explaining part of the observed between-center variability, with the ultimate aim of helping to improve local infection control and antifungal stewardship projects and interventions.


Assuntos
Candidíase Invasiva/complicações , Idoso , Candidíase Invasiva/epidemiologia , Infecção Hospitalar/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/normas , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco
5.
J Exp Biol ; 221(Pt 14)2018 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-29798844

RESUMO

The fish gut is responsible for numerous potentially energetically costly processes, yet little is known about its metabolism. Here, we provide the first in vivo measurements of aerobic metabolism of the gut in a teleost fish by measuring gut blood flow, as well as arterial and portal venous oxygen content. At 10°C, gut oxygen uptake rate was 4.3±0.5 ml O2 h-1 kg-1 (∼11% of whole-animal oxygen uptake). Following acute warming to 15°C, gut blood flow increased ∼3.4-fold and gut oxygen uptake rate increased ∼3.7-fold (16.0±3.3 ml O2 h-1 kg-1), now representing ∼25% of whole-animal oxygen uptake. Although gut blood flow decreased following an acute stress event at 15°C, gut oxygen uptake remained unchanged as a result of a ∼2-fold increase in oxygen extraction. The high metabolic thermal sensitivity of the gut could have important implications for the overall aerobic capacity and performance of fish in a warming world and warrants further investigation.


Assuntos
Trato Gastrointestinal/fisiologia , Temperatura Alta/efeitos adversos , Oncorhynchus mykiss/fisiologia , Oxigênio/metabolismo , Aerobiose , Animais , Respiração Celular/fisiologia , Feminino , Masculino , Estresse Fisiológico
6.
J Fish Biol ; 93(3): 519-527, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29934951

RESUMO

The aim of the current work was to elucidate if there is a connection between stress-induced decrease in coeliacomesenteric artery blood flow (i.e. gastrointestinal blood flow; GBF) and disruption of the intestinal primary barrier in rainbow trout Oncorhynchus mykiss. Upon initiation of a 15 min acute chasing stress, the GBF decreased instantly by c. 92%. The GBF then slowly increased and reached c. 28% of resting values at the end of the stress protocol. After the stress was ceased, the GBF slowly increased and returned to resting values within c. 45 min. Intestinal permeability assessment in an Ussing-chambers set-up revealed impaired intestinal barrier function 24 h after stress. When the stress-induced GBF reduction was mimicked by an experimental occlusion of the coeliacomesenteric artery for 15 min followed by 24 h recovery, no effect on intestinal barrier function was observed. These results suggest that no direct causal relationship can be found between the GBF reduction and development of intestinal barrier dysfunction following periods of acute stress in this species of fish.


Assuntos
Trato Gastrointestinal/irrigação sanguínea , Mucosa Intestinal/metabolismo , Oncorhynchus mykiss/fisiologia , Circulação Esplâncnica , Estresse Psicológico/fisiopatologia , Animais , Permeabilidade
7.
Antimicrob Agents Chemother ; 60(11): 6924-6927, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27572403

RESUMO

Extended-spectrum-cephalosporin-resistant Enterobacteriaceae are a public health concern due to limited treatment options. Here, we report on the occurrence and the molecular characteristics of extended-spectrum-cephalosporin-resistant Enterobacteriaceae recovered from wild birds (kelp gulls). Our results revealed kelp gulls as a reservoir of various extended-spectrum cephalosporinase genes associated with different genetic platforms. In addition, we report for the first time the presence of a known epidemic clone of Salmonella enterica serotype Heidelberg (JF6X01.0326/XbaI.1966) among wild birds.


Assuntos
Resistência às Cefalosporinas/genética , Charadriiformes/microbiologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/genética , Animais , Antibacterianos/farmacologia , Resistência às Cefalosporinas/efeitos dos fármacos , Cefalosporinase/genética , Cefalosporinas/farmacologia , Enterobacteriaceae/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Plasmídeos/genética , Salmonella enterica/efeitos dos fármacos , Salmonella enterica/genética , América do Sul
8.
BMC Public Health ; 14: 66, 2014 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-24450797

RESUMO

BACKGROUND: Effective screening programs are urgently needed to provide undiagnosed hepatitis C virus (HCV)-infected individuals with therapy. This systematic review of characteristics and outcomes of screening programs for HCV focuses on strategies to identify HCV risk groups hidden in the general population. METHODS: We conducted a comprehensive search of MEDLINE and EMBASE databases for articles published between 1991-2010, including studies that screened the general population using either a newly developed (nonintegrated) screening program or one integrated in existing health care facilities. Look-back studies, prevalence studies, and programs targeting high-risk groups in care (e.g., current drug users) were excluded. RESULTS: After reviewing 7052 studies, we identified 67 screening programs: 24 nonintegrated; 41 programs integrated in a variety of health care facilities (e.g., general practitioner); and 2 programs with both integrated and nonintegrated strategies. Together, these programs identified approximately 25,700 HCV-infected individuals. In general, higher HCV prevalence was found in programs in countries with intermediate to high HCV prevalence, in psychiatric clinics, and in programs that used a prescreening selection based on HCV risk factors. Only 6 programs used a comparison group for evaluation purposes, and 1 program used theory about effective promotion for screening. Comparison of the programs and their effectiveness was hampered by lack of reported data on program characteristics, clinical follow-up, and type of diagnostic test. CONCLUSIONS: A prescreening selection based on risk factors can increase the efficiency of screening in low-prevalence populations, and we need programs with comparison groups to evaluate effectiveness. Also, program characteristics such as type of diagnostic test, screening uptake, and clinical outcomes should be reported systematically.


Assuntos
Hepacivirus/isolamento & purificação , Hepatite C/diagnóstico , Programas de Rastreamento/métodos , Idoso , Hepatite C/epidemiologia , Humanos , Prevalência , Avaliação de Programas e Projetos de Saúde , Fatores de Risco
9.
Acta Vet Scand ; 65(1): 15, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-37020257

RESUMO

BACKGROUND: Official meat inspections at small-scale slaughterhouses and game-handling establishments in geographically remote areas place a heavy burden on the meat-producing food business operators. By performing meat inspections remotely using live-streamed video, instead of on-site, the official control could meet the goals of sustainability, resilience and logistics. We investigated the agreement between the two approaches at pig slaughter. Two official veterinarians (OVs) inspected 400 pig carcasses at a Swedish slaughterhouse, with each pig being inspected on site by one OV and remotely by the other. After a period of 3 to 6 months, video recordings of the remote inspections were assessed again by the same OVs, thus enabling direct comparisons of previous on-site inspections and renewed video-based inspections within the same OV. RESULTS: Agreement across 22 finding codes was generally very high for both OVs. In all but one case (whether to fully condemn a carcass), for both OVs, Prevalence-Adjusted Bias-Adjusted kappa was well above 0.8, indicating 'almost perfect agreement'. CONCLUSIONS: This study supports earlier findings that reliable post-mortem inspections can be performed using video, and indicates higher agreement between remote and on-site inspections if the same OV performs both.


Assuntos
Inspeção de Alimentos , Carne de Porco , Animais , Matadouros , Prevalência , Suínos
10.
J Crit Care ; 76: 154272, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36801598

RESUMO

PURPOSE: COVID-19 associated pulmonary aspergillosis (CAPA) is associated with increased morbidity and mortality in ICU patients. We investigated the incidence of, risk factors for and potential benefit of a pre-emptive screening strategy for CAPA in ICUs in the Netherlands/Belgium during immunosuppressive COVID-19 treatment. MATERIALS AND METHODS: A retrospective, observational, multicentre study was performed from September 2020-April 2021 including patients admitted to the ICU who had undergone diagnostics for CAPA. Patients were classified based on 2020 ECMM/ISHAM consensus criteria. RESULTS: CAPA was diagnosed in 295/1977 (14.9%) patients. Corticosteroids were administered to 97.1% of patients and interleukin-6 inhibitors (anti-IL-6) to 23.5%. EORTC/MSGERC host factors or treatment with anti-IL-6 with or without corticosteroids were not risk factors for CAPA. Ninety-day mortality was 65.3% (145/222) in patients with CAPA compared to 53.7% (176/328) without CAPA (p = 0.008). Median time from ICU admission to CAPA diagnosis was 12 days. Pre-emptive screening for CAPA was not associated with earlier diagnosis or reduced mortality compared to a reactive diagnostic strategy. CONCLUSIONS: CAPA is an indicator of a protracted course of a COVID-19 infection. No benefit of pre-emptive screening was observed, but prospective studies comparing pre-defined strategies would be required to confirm this observation.


Assuntos
COVID-19 , Aspergilose Pulmonar , Humanos , Incidência , Tratamento Farmacológico da COVID-19 , Estudos Prospectivos , Estudos Retrospectivos
11.
EFSA J ; 21(5): e07992, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37200855

RESUMO

This Scientific Opinion concerns the welfare of Domestic ducks (Anas platyrhynchos domesticus), Muscovy ducks (Cairina moschata domesticus) and their hybrids (Mule ducks), Domestic geese (Anser anser f. domesticus) and Japanese quail (Coturnix japonica) in relation to the rearing of breeders, birds for meat, Muscovy and Mule ducks and Domestic geese for foie gras and layer Japanese quail for egg production. The most common husbandry systems (HSs) in the European Union are described for each animal species and category. The following welfare consequences are described and assessed for each species: restriction of movement, injuries (bone lesions including fractures and dislocations, soft tissue lesions and integument damage and locomotory disorders including lameness), group stress, inability to perform comfort behaviour, inability to perform exploratory or foraging behaviour and inability to express maternal behaviour (related to prelaying and nesting behaviours). Animal-based measures relevant for the assessment of these welfare consequences were identified and described. The relevant hazards leading to the welfare consequences in the different HSs were identified. Specific factors such as space allowance (including minimum enclosure area and height) per bird, group size, floor quality, characteristics of nesting facilities and enrichment provided (including access to water to fulfil biological needs) were assessed in relation to the welfare consequences and, recommendations on how to prevent the welfare consequences were provided in a quantitative or qualitative way.

12.
Animals (Basel) ; 12(4)2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35203199

RESUMO

Transporting cattle from farm to slaughterhouse is often stressful for the animal, which can impair the meat quality. With the gunshot method, the animal is stunned with a rifle shot while together with familiar herd members in their home environment, exsanguinated and transported to a nearby slaughterhouse. Aiming to assess the consequences for animal welfare and food safety, 20 Hereford steers aged 18-54 months were shot with .22 Magnum ammunition from an elevated position and distance of 6-12 m. Each time, only one out of four to seven animals in a 16 × 10 m corral was shot. Dressing was done on farm. Based on the animals' behaviour and blood concentrations of cortisol, glucose and lactate, stress levels before shooting were low. Eleven animals were deeply stunned, the consciousness of seven others was ambiguous, and two were poorly stunned. Two animals were reshot. The bleed-out was satisfactory for all animals, and little or no faecal contamination was found on the carcasses. We conclude that the gunshot method is applicable to large beef steers while maintaining a satisfactory level of animal welfare and food safety, provided that the necessary conditions can be attained.

13.
Animals (Basel) ; 12(11)2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35681905

RESUMO

In Sweden, the County Administrative Board (CAB) and Swedish Trotting Association (STA) both perform animal welfare inspections of the premises of trotting horse trainers. The CAB inspection checks for compliance with the legislation, and the STA inspection checks for compliance with the private 'Trotter Health Standard', which mainly sets the same requirements as the legislation. This study investigated the views of trainers on these inspections both as separate events and in relation to each other. A digital questionnaire was sent out to trotting horse trainers in Sweden during spring 2021, and 396 trainers responded. Descriptive and statistical analyses were used to evaluate the responses. In general, the trainers reported positive experiences of both the CAB and STA inspections, but they had consistently more positive views about the private STA inspections than the official CAB inspections. The outcome of the inspections, i.e., non-compliance or not, did not affect trainers' perceptions of the inspections, but inspectors' knowledge, manner, and responsiveness had a strong effect. The trainers were generally satisfied with the current control system but would like better coordination between the different inspections.

14.
Animals (Basel) ; 12(22)2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36428371

RESUMO

Hot-iron branding is still commonly performed in cattle farming in tropical countries, and possibly has negative consequences for animal welfare and weight gain. This study examined the behavioural and weight gain responses of pure and crossbred Nellore heifer calves subjected to hot-iron branding on the cheek, without and with use of anaesthesia and analgesia. Ninety-two heifer calves, around 120 days old, were studied prospectively when subjected to hot-iron branding on the cheek (a statutory procedure in Brazil following brucellosis vaccination). Four randomly selected groups of calves were allocated to four treatments: no pain control (CO); subcutaneous anaesthetic local block (LA); intramuscular analgesia (meloxicam) (LT); and local anaesthesia plus meloxicam (LL). Behaviour, flight speed and body weight were evaluated before, during, and five (5-d) and 60 days (60-d) after branding. For these parameters, the only difference observed was higher tension in the CO group 5-d post-branding, suggesting a short-term negative effect of branding without pain control. The limited effects of the pain control treatments suggest interference in pain assessment by other factors, such as expression of fear and stress. Despite the lack of differences observed in behaviour and production parameters, facial hot-iron branding is an obvious welfare issue and, due to the additional handling involved, adoption of a simple pain relief protocol is not sufficient to minimise the welfare impact.

15.
Infect Dis Ther ; 11(2): 827-840, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35182353

RESUMO

INTRODUCTION: Intra-abdominal infections represent the second most frequently acquired infection in the intensive care unit (ICU), with mortality rates ranging from 20% to 50%. Candida spp. may be responsible for up to 10-30% of cases. This study assesses risk factors for development of intra-abdominal candidiasis (IAC) among patients admitted to ICU. METHODS: We performed a case-control study in 26 European ICUs during the period January 2015-December 2016. Patients at least 18 years old who developed an episode of microbiologically documented IAC during their stay in the ICU (at least 48 h after admission) served as the case cohort. The control group consisted of adult patients who did not develop episodes of IAC during ICU admission. Matching was performed at a ratio of 1:1 according to time at risk (i.e. controls had to have at least the same length of ICU stay as their matched cases prior to IAC onset), ICU ward and period of study. RESULTS: During the study period, 101 case patients with a diagnosis of IAC were included in the study. On univariate analysis, severe hepatic failure, prior receipt of antibiotics, prior receipt of parenteral nutrition, abdominal drain, prior bacterial infection, anastomotic leakage, recurrent gastrointestinal perforation, prior receipt of antifungal drugs and higher median number of abdominal surgical interventions were associated with IAC development. On multivariate analysis, recurrent gastrointestinal perforation (OR 13.90; 95% CI 2.65-72.82, p = 0.002), anastomotic leakage (OR 6.61; 95% CI 1.98-21.99, p = 0.002), abdominal drain (OR 6.58; 95% CI 1.73-25.06, p = 0.006), prior receipt of antifungal drugs (OR 4.26; 95% CI 1.04-17.46, p = 0.04) or antibiotics (OR 3.78; 95% CI 1.32-10.52, p = 0.01) were independently associated with IAC. CONCLUSIONS: Gastrointestinal perforation, anastomotic leakage, abdominal drain and prior receipt of antifungals or antibiotics may help to identify critically ill patients with higher probability of developing IAC. Prospective studies are needed to identify which patients will benefit from early antifungal treatment.

16.
Clin Gastroenterol Hepatol ; 9(9): 786-792.e1, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21699803

RESUMO

BACKGROUND & AIMS: Most studies of progression of chronic hepatitis C virus (cHCV) infection were conducted in hospital settings and were therefore biased for patients with severe disease. We evaluated the long-term outcomes of hepatitis C virus (HCV) infection among injecting drug users, recruited from outside the hospital setting, and examined the effect of cHCV on mortality after seroconversion. METHODS: We studied data from 106 seroconverters with a documented or estimated date of HCV seroconversion. Cox proportional hazards analysis was used to determine the effect of HCV persistence, compared with HCV clearance, on survival after HCV seroconversion. The median follow-up time was 14.8 years (interquartile range, 7.8-19.6). RESULTS: cHCV infection developed in 71 of the subjects (67%; 95% confidence interval [CI], 57%-76%); 33 subjects died. One HCV-related death was observed 23 years after HCV seroconversion. Most causes of death were non-natural (n = 12) or acquired immune deficiency syndrome-related (n = 8). The effect of cHCV on mortality was nonproportional over time. When survival time was analyzed separately for 0-5 years, >5-10 years, and >10 years after HCV seroconversion, the age-adjusted hazard ratios for cHCV were 0.59 (95% CI, 0.16-2.20), 1.76 (95% CI, 0.36-8.53), and 8.28 (95% CI, 1.10-64.55), respectively, compared with resolved HCV infection. CONCLUSIONS: cHCV infection does not affect overall mortality in the first decade after seroconversion, compared with individuals who resolve HCV infection; however, during the second decade after infection, individuals with cHCV have an increased risk for all-cause mortality. Mortality from liver-related causes was low but might have been masked by competing mortality.


Assuntos
Hepatite C/complicações , Hepatite C/mortalidade , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/mortalidade , Adulto , Estudos de Coortes , Usuários de Drogas , Feminino , Seguimentos , Humanos , Incidência , Masculino , Estudos Prospectivos , Análise de Sobrevida
17.
Animals (Basel) ; 11(10)2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34679921

RESUMO

Sweden is often seen as a leading country in animal welfare and legislation, but some recent amendments to the legislation are perceived as relaxing animal welfare requirements in order to improve the competitiveness of the relevant industry and of farmers. In this study, we analysed the suggested and actual changes in the Swedish national animal welfare regulations relating to horses, cattle and pigs between 1988 and 2019 and the consequences for the intended animal welfare level. The regulations and amendments, including the proposals, the written motivations, the stakeholders' written responses to the proposed amendments and the final amendments, were scrutinised in detail. A sample of 77 requirements was then selected to assess whether and how the animal welfare level was affected by these legislative changes. The results indicated that the animal welfare protection level for cattle, pigs and horses increased overall during the 30-year period, but that a number of specific requirements had been relaxed to meet objectives other than animal welfare. It was more difficult to determine whether animal welfare improved in practice during the same period, due to the lack of systematic evaluations of the consequences of amending the regulations. Future evaluations are needed to evaluate the outcome of new legislative requirements and to monitor whether they serve their purpose in practice.

18.
ALTEX ; 38(3): 477-489, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33786636

RESUMO

The implementation of the 3Rs (replacement, reduction and refinement) is emphasized in EU Directive 2010/63. The task of the animal welfare bodies (AWB) is to strengthen animal welfare and develop the 3Rs at research animal facilities. In 2016, we surveyed the knowledge on, attitudes towards and implementation of the 3Rs within AWBs at eight major Swedish universities. Based on responses of 34 closed-ended questions from 44 of 90 AWB members, the overall attitude towards the 3Rs was positive. AWB members did not believe that the 3Rs slow down innovation or result in increased costs, and refinement was considered beneficial for research quality. AWB members were particularly positive towards refinement questions in the survey. A majority of the AWB members predicted that alternative methods will never replace animal use. Researchers as a group represented in the AWBs were significantly less positive towards the 3Rs compared to the group of veterinarians. The tasks of the AWBs, e.g., giving advice on the 3Rs and following up on animal use in projects, were often not carried out in the AWB or not known by the respondents. Our results indicate a need for more practical and regulatory guidance and support to the AWBs. To reach the goal of the EU Directive to phase out animal use in research and education, we suggest that technical expertise in replacement techniques is included in the AWBs. We emphasize the need to strengthen the awareness of the 3Rs among researchers at Swedish universities.


Assuntos
Experimentação Animal , Universidades , Alternativas aos Testes com Animais , Bem-Estar do Animal , Animais , Conhecimentos, Atitudes e Prática em Saúde , Inquéritos e Questionários , Suécia
19.
Animals (Basel) ; 11(7)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202333

RESUMO

A key issue in food governance and public administration is achieving coordinated implementation of policies. This study addressed this issue by systematically comparing the governance of animal welfare in Norway and Sweden, using published papers, reports, and legal and other public information, combined with survey and interview data generated in a larger research project (ANIWEL). Governing animal welfare includes a number of issues that are relevant across different sectors and policy areas, such as ethical aspects, choice of legal tools, compliance mechanisms and achieving uniform control. Based on the challenges identified in coordinating animal welfare in Norway and Sweden, relevant organisational preconditions for achieving uniform and consistent compliance were assessed. The results showed that Sweden's organisation may need more horizontal coordination, since its animal welfare management is divided between multiple organisational units (Swedish Board of Agriculture, National Food Agency and 21 regional County Administration Boards). Coordination in Norway is managed solely by the governmental agency Norwegian Food Safety Authority (NFSA), which has the full responsibility for inspection and control of food safety, animal health, plant health, as well as animal welfare. Thus, Norway has better preconditions than Sweden for achieving uniformity in animal welfare administration. However, in Norway, the safeguards for the rule of law might be an issue, due to NFSA acting as de facto "inspector", "prosecutor" and "judge".

20.
Animals (Basel) ; 11(2)2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33546170

RESUMO

The societal demand for good farm animal welfare (FAW) has increased over time. Yet, very little is known about the economic consequences of improvements in FAW in cow-calf operations. This study investigates on-farm economic consequences of improved FAW measures in cow-calf operations. It uses a stochastic partial budgeting approach to examine the relationship between contribution margins and improvements in FAW in terms of increased space allowance for a typical Swedish cow-calf operation, as compared to current practices. In the current practice, a cow should be given at least 5 m2 and the calf 2.2 m2. We found that a 0.5 m2 increase in space allowance per calf (achieved by a corresponding reduction of herd size) was associated with a 6.9 to 18.7% reduction in contribution margins in the short term. Our analysis does not include possible indirect gains like decrease in disease incidence and enhanced non-use or 'soft' values associated with increased FAW. However, our analysis indicates that high FAW standards can be costly and careful cost-benefit analysis should be a part of decision-making processes regarding FAW standards. Our results also suggest a need for government support payments and/or the development of market mechanisms to stimulate farmers to continue producing livestock-based foods with high FAW.

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