RESUMO
OBJECTIVES: This study aims to evaluate if low levels of serum maternal pregnancy associated plasma protein-A (PAPP-A) during the first trimester are related to increased umbilical artery pulsatility index (UA PI) later in pregnancy, in cases of estimated fetal weight between the 3rd and 10th percentiles, in order to establish PAPP-A as a predictor of this particular cases of fetal growth restriction (FGR). METHODS: An observational, retrospective cohort study, conducted at a tertiary University Hospital located in Oporto, Portugal. Pregnant women who did the first trimester combined screening, between May 2013 and June 2020 and gave birth in the same hospital, with an estimated fetal weight (EFW) between the 3rd and 10th percentiles were included. The primary outcome is the difference in increased UA PI prevalence between two groups: PAPP-A<0.45 MoM and PAPP-A≥0.45 MoM. As secondary outcomes were evaluated differences in neonatal weight, gestational age at delivery, cesarean delivery, neonatal intensive care unit hospitalization, 5-min Apgar score below 7 and live birth rate between the same two groups. RESULTS: We included 664 pregnancies: 110 cases of PAPP-A<0.45 MoM and 554 cases with PAPP-A≥0.45 MoM. Increased UA PI prevalence, which was the primary outcome of this study, was significantly different between the two groups (p=0.005), as the PAPP-A<0.45 MoM group presents a higher prevalence (12.7â¯%) when compared to the PAPP-A≥0.45 MoM group (5.4â¯%). The secondary outcome cesarean delivery rate was significantly different between the groups (p=0.014), as the PAPP-A<0.45 MoM group presents a higher prevalence (42.7â¯%) than the PAPP-A≥0.45 MoM group (30.1â¯%). No other secondary outcomes showed differences between the two groups. CONCLUSIONS: There is an association of low serum maternal PAPP-A (<0.45 MoM) during the first trimester and increased UA PI (>95th percentile) later in pregnancy, in cases of EFW between the 3rd and 10th percentiles. However, this association is not strong enough alone for low PAPP-A to be a reliable predictor of increased UA PI in this population.
Assuntos
Peso Fetal , Proteína Plasmática A Associada à Gravidez , Recém-Nascido , Gravidez , Humanos , Feminino , Artérias Umbilicais/diagnóstico por imagem , Estudos Retrospectivos , Ultrassonografia Pré-Natal , Retardo do Crescimento Fetal/diagnóstico , Idade GestacionalRESUMO
This brief report presents the findings of an epidemiological investigation into a large-scale outbreak of norovirus gastroenteritis that occurred in a hotel in Algarve, Portugal, in August 2022. A total of 244 cases were reported, primarily affecting Portuguese families, with the parents aged 40-50 years and the children aged 0-19 years. Reported symptoms included vomiting, nausea, abdominal pain, and diarrhoea. Norovirus genotype GI.3 [P3] was detected in stool samples from eight probable cases, while food samples tested negative for norovirus and common pathogenic bacteria. The investigation data collected suggest that the source of the outbreak was likely in the hotel's common areas, with subsequent person-to-person transmission in other areas. The final report emphasizes the importance of improving outbreak prevention and control measures, including the development of a foodborne outbreak investigation protocol, the establishment of an outbreak response team, and the enhancement of regional laboratory capacity.
Assuntos
Norovirus , Criança , Humanos , Norovirus/genética , Surtos de Doenças , Diarreia , Portugal/epidemiologia , VômitoRESUMO
Obesity is a predictive factor for the development of nonalcoholic steatohepatitis (NASH). Although some of the mechanisms associated with NASH development are still elusive, its pathogenesis relies on a complex broad spectrum of (interconnected) metabolic-based disorders. We analyzed the effects of voluntary physical activity (VPA) and endurance training (ET), as preventive and therapeutic nonpharmacological strategies, respectively, against hepatic endoplasmic reticulum (ER) stress, ER-related proapoptotic signaling, and oxidative stress in an animal model of high-fat diet (HFD)-induced NASH. Adult male Sprague-Dawley rats were divided into standard control liquid diet (SCLD) or HFD groups, with sedentary, VPA, and ET subgroups in both (sedentary animals with access to SCLD [SS], voluntarily physically active animals with access to SCLD [SV], and endurance-trained animals with access to SCLD [ST] in the former and sedentary animals with access to liquid HFD [HS], voluntarily physically active animals with access to liquid HFD [HV], and endurance-trained animals with access to liquid HFD [HT] in the latter, respectively). Hepatic ER stress and ER-related proapoptotic signaling were evaluated by Western blot and reverse transcriptase-polymerase chain reaction; redox status was evaluated through quantification of lipid peroxidation, protein carbonyls groups, and glutathione levels as well as antioxidant enzymes activity. In SCLD-treated animals, VPA significantly decreased eukaryotic initiation factor-2 alpha (eIF2α). In HFD-treated animals, VPA significantly decreased eIF2α and phospho-inositol requiring enzyme-1 alpha (IRE1α) but ET significantly decreased eIF2α and significantly increased both spliced X-box binding protein 1 (sXBP1) and unspliced X-box binding protein 1; a significant increase of phosphorylated-eIF2α (p-eIF2α) to eIF2α ratio occurred in ET versus VPA. HS compared to SS disclosed a significant increase of total and reduced glutathione, HV compared to SV a significant increase of oxidized glutathione, HT compared to ST a significant increase of p-eIF2α to eIF2α ratio and sXBP1. Physical exercise counteracts NASH-related ER stress and its associated deleterious consequences through a positive and dynamical modulation of the hepatic IRE1α-X-box binding protein 1 pathway.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Masculino , Ratos , Estresse do Retículo Endoplasmático , Endorribonucleases/metabolismo , Fator de Iniciação 2 em Eucariotos/metabolismo , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas Serina-Treonina Quinases , Ratos Sprague-Dawley , Proteína 1 de Ligação a X-Box , Condicionamento Físico AnimalRESUMO
The lipid mediators, platelet-activating factor (PAF) and lysophosphatidylcholine (LPC), play relevant pathophysiological roles in Trypanosoma cruzi infection. Several species of LPC, including C18:1 LPC, which mimics the effects of PAF, are synthesized by T. cruzi. The present study identified a receptor in T. cruzi, which was predicted to bind to PAF, and found it to be homologous to members of the progestin and adiponectin family of receptors (PAQRs). We constructed a three-dimensional model of the T. cruzi PAQR (TcPAQR) and performed molecular docking to predict the interactions of the TcPAQR model with C16:0 PAF and C18:1 LPC. We knocked out T. cruzi PAQR (TcPAQR) gene and confirmed the identity of the expressed protein through immunoblotting and immunofluorescence assays using an anti-human PAQR antibody. Wild-type and knockout (KO) parasites were also used to investigate the in vitro cell differentiation and interactions with peritoneal mouse macrophages; TcPAQR KO parasites were unable to react to C16:0 PAF or C18:1 LPC. Our data are highly suggestive that PAF and LPC act through TcPAQR in T. cruzi, triggering its cellular differentiation and ability to infect macrophages.
Assuntos
Lisofosfatidilcolinas/metabolismo , Fator de Ativação de Plaquetas/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Trypanosoma cruzi/genética , Trypanosoma cruzi/metabolismo , Sequência de Aminoácidos , Animais , Diferenciação Celular , Doença de Chagas/parasitologia , Técnicas de Inativação de Genes/métodos , Interações Hospedeiro-Parasita , Humanos , Lisofosfatidilcolinas/química , Macrófagos , Camundongos , Simulação de Acoplamento Molecular , Filogenia , Fator de Ativação de Plaquetas/química , Conformação Proteica , Proteínas de Protozoários/química , Receptores de Adiponectina/química , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Receptores de Progesterona/química , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Trypanosoma cruzi/químicaRESUMO
BACKGROUND: Neuregulin-1 (NRG-1) is a stress-mediated transmembrane growth factor. Reduced myocardial damage and higher NRG-1 levels upon treatment with remote ischemic conditioning (RIC) has been described in rats. However, the role of NRG-1 in patients with acute myocardial infarction (MI) is unknown. Thus, we conducted a post hoc analysis of a randomized controlled trial that tested RIC in patients with MI scheduled for primary percutaneous coronary intervention (PCI). METHODS: Blood was drawn from 30 patients before RIC/PCI, within 1 hour, 4 days and 1 month later. Median left ventricular ejection fraction (LVEF) in the overall study population following MI was 48.5%. RESULTS: NRG-1 plasma levels decreased significantly following PCI/RIC and remained decreased up to 1 month following MI (p < 0.0001). We observed no association of NRG-1 with other variables, including total ischemic time, LVEF or RIC. CONCLUSIONS: Thus, we identified NRG-1 may be independently affected by MI. However, further large clinical trials are warranted to clarify this hypothesis.
Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Animais , Humanos , Neuregulina-1 , Intervenção Coronária Percutânea/efeitos adversos , Ratos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Volume Sistólico , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
In this work, we show how the mechanical properties of the cellular microenvironment modulate the growth of tumour spheroids. Based on the composition of the extracellular matrix, its stiffness and architecture can significantly vary, subsequently influencing cell movement and tumour growth. However, it is still unclear exactly how both of these processes are regulated by the matrix composition. Here, we present a centre-based computational model that describes how collagen density, which modulates the steric hindrance properties of the matrix, governs individual cell migration and, consequently, leads to the formation of multicellular clusters of varying size. The model was calibrated using previously published experimental data, replicating a set of experiments in which cells were seeded in collagen matrices of different collagen densities, hence producing distinct mechanical properties. At an initial stage, we tracked individual cell trajectories and speeds. Subsequently, the formation of multicellular clusters was also analysed by quantifying their size. Overall, the results showed that our model could accurately replicate what was previously seen experimentally. Specifically, we showed that cells seeded in matrices with low collagen density tended to migrate more. Accordingly, cells strayed away from their original cluster and thus promoted the formation of small structures. In contrast, we also showed that high collagen densities hindered cell migration and produced multicellular clusters with increased volume. In conclusion, this model not only establishes a relation between matrix density and individual cell migration but also showcases how migration, or its inhibition, modulates tumour growth.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Esferoides Celulares , Algoritmos , Calibragem , Movimento Celular , Células Cultivadas , Microambiente Celular , Colágeno/química , Simulação por Computador , Matriz Extracelular/metabolismo , Fibroblastos , Humanos , Estresse Mecânico , Microambiente TumoralRESUMO
Blood-contacting devices are increasingly important for the management of cardiovascular diseases. Poly(ethylene glycol) (PEG) hydrogels represent one of the most explored hydrogels to date. However, they are mechanically weak, which prevents their use in load-bearing biomedical applications (e.g., vascular grafts, cardiac valves). Graphene and its derivatives, which have outstanding mechanical properties, a very high specific surface area, and good compatibility with many polymer matrices, are promising candidates to solve this challenge. In this work, we propose the use of graphene-based materials as nanofillers for mechanical reinforcement of PEG hydrogels, and we obtain composites that are stiffer and stronger than, and as anti-adhesive as, neat PEG hydrogels. Results show that single-layer and few-layer graphene oxide can strengthen PEG hydrogels, increasing their stiffness up to 6-fold and their strength 14-fold upon incorporation of 4% w/v (40 mg/mL) graphene oxide. The composites are cytocompatible and remain anti-adhesive towards endothelial cells, human platelets and Staphylococcus aureus, similar to neat hydrogels. To the best of our knowledge, this is the first work to report such an increase of the tensile properties of PEG hydrogels using graphene-based materials as fillers. This work paves the way for the exploitation of PEG hydrogels as a backbone material for load-bearing applications.
Assuntos
Grafite/química , Hidrogéis/química , Polietilenoglicóis/química , Adesivos/química , Materiais Biocompatíveis/química , Linhagem Celular , Células Endoteliais da Veia Umbilical Humana , Humanos , Polímeros/química , Engenharia Tecidual/métodosRESUMO
Three-dimensional (3D) in vitro models, such as organ-on-a-chip platforms, are an emerging and effective technology that allows the replication of the function of tissues and organs, bridging the gap amid the conventional models based on planar cell cultures or animals and the complex human system. Hence, they have been increasingly used for biomedical research, such as drug discovery and personalized healthcare. A promising strategy for their fabrication is 3D printing, a layer-by-layer fabrication process that allows the construction of complex 3D structures. In contrast, 3D bioprinting, an evolving biofabrication method, focuses on the accurate deposition of hydrogel bioinks loaded with cells to construct tissue-engineered structures. The purpose of the present work is to conduct a systematic review (SR) of the published literature, according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, providing a source of information on the evolution of organ-on-a-chip platforms obtained resorting to 3D printing and bioprinting techniques. In the literature search, PubMed, Scopus, and ScienceDirect databases were used, and two authors independently performed the search, study selection, and data extraction. The goal of this SR is to highlight the importance and advantages of using 3D printing techniques in obtaining organ-on-a-chip platforms, and also to identify potential gaps and future perspectives in this research field. Additionally, challenges in integrating sensors in organs-on-chip platforms are briefly investigated and discussed.
Assuntos
Bioimpressão , Dispositivos Lab-On-A-Chip , Animais , Humanos , Hidrogéis , Impressão Tridimensional , Engenharia TecidualRESUMO
BACKGROUND: Tenascin-C (TN-C) plays a maladaptive role in left ventricular (LV) hypertrophy following pressure overload. However, the role of TN-C in LV regression following mechanical unloading is unknown. METHODS: LV hypertrophy was induced by transverse aortic constriction for 10 weeks followed by debanding for 2 weeks in wild type (Wt) and TN-C knockout (TN-C KO) mice. Cardiac function was assessed by serial magnetic resonance imaging. The expression of fibrotic markers and drivers (angiotensin-converting enzyme-1, ACE-1) was determined in LV tissue as well as human cardiac fibroblasts (HCFs) after TN-C treatment. RESULTS: Chronic pressure overload resulted in a significant decline in cardiac function associated with LV dilation as well as upregulation of TN-C, collagen 1 (Col 1), and ACE-1 in Wt as compared to TN-C KO mice. Reverse remodeling in Wt mice partially improved cardiac function and fibrotic marker expression; however, TN-C protein expression remained unchanged. In HCF, TN-C strongly induced the upregulation of ACE 1 and Col 1. CONCLUSIONS: Pressure overload, when lasting long enough to induce HF, has less potential for reverse remodeling in mice. This may be due to significant upregulation of TN-C expression, which stimulates ACE 1, Col 1, and alpha-smooth muscle actin (α-SMA) upregulation in fibroblasts. Consequently, addressing TN-C in LV hypertrophy might open a new window for future therapeutics.
Assuntos
Aorta/fisiologia , Tenascina/metabolismo , Remodelação Ventricular , Animais , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/metabolismo , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Constrição Patológica , Fibroblastos/metabolismo , Ventrículos do Coração/metabolismo , Humanos , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Knockout , Peptidil Dipeptidase A/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Volume Sistólico , Função VentricularRESUMO
We report a multidrug-resistant Neisseria gonorrhoeae exhibiting resistance to ceftriaxone and cefixime, isolated in Portugal in 2019. Whole-genome sequencing was performed for typing and identification of genetic determinants of antimicrobial resistance. Because of its antimicrobial susceptibility profile, awareness should be raised for the circulation of this strain.
Assuntos
Antibacterianos/farmacologia , Cefixima/farmacologia , Ceftriaxona/farmacologia , Gonorreia/tratamento farmacológico , Neisseria gonorrhoeae/efeitos dos fármacos , Adulto , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Gonorreia/diagnóstico , Humanos , Masculino , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/isolamento & purificação , PortugalRESUMO
In many social species, individuals communally defend resources from conspecific outsiders. Participation in defence and in associated within-group interactions, both during and after contests with outgroup rivals, is expected to vary between group members because the threat presented by different outsiders is not the same to each individual. However, experimental tests examining both the contributions to, and the consequences of, outgroup conflict for all group members are lacking. Using groups of the cichlid Neolamprologus pulcher, we simulated territorial intrusions by different-sized female rivals and altered the potential contribution of subordinate females to defence. Dominant females and subordinate females defended significantly more against size- and rank-matched intruders, while males displayed lower and less variable levels of defence. Large and small, but not intermediate-sized, intruders induced increased levels of within-group aggression during intrusions, which was targeted at the subordinate females. Preventing subordinate females from helping in territorial defence led to significant decreases in post-contest within-group and female-specific submissive and affiliative displays. Together, these results show that the defensive contributions of group members vary greatly depending both on their own traits and on intruder identity, and this variation has significant consequences for within-group social dynamics both during and in the aftermath of outgroup contests.
Assuntos
Ciclídeos/fisiologia , Comportamento Social , Agressão , Animais , Feminino , Masculino , TerritorialidadeRESUMO
BACKGROUND/OBJECTIVES: The browning of white adipose tissue (WAT) has been in the spotlight during the last years, becoming an attractive approach to combat obesity. Melanocortin neuropeptides, such as α-melanocyte-stimulating hormone (α-MSH), are well-known regulators of appetite at the central nervous system, but its role in adipocyte metabolism is poorly elucidated. This study sought to verify if α-MSH can induce transdifferentiation of white to brown/beige adipocytes and to determine whether it can ameliorate the obesity phenotype. METHODS: The browning effect of α-MSH was determined in isolated adipocytes using the 3T3-L1 cell line and in inguinal subcutaneous adipose tissue (ingWAT) of diet-induced obese (DIO) mice by quantifying the expression of browning hallmark genes, oxygen consumption, and mitochondrial biogenesis. α-MSH protection from diet-induced obesity was evaluated by analyzing mice body weight, fat mass, and lipid and glucose serum profiles. RESULTS: Here, we report that α-MSH activates a thermogenic gene program and increases the mitochondrial respiratory rate in 3T3-L1 adipocytes and ingWAT of DIO mice. Without affecting food intake, peripheral administration of α-MSH decreases body weight and ingWAT mass, promoting a significant rise in the number of smaller adipocytes, whereas it lowered the larger ones. Additionally, there was an increase in the mass of brown adipose tissue. Browning activation occurs concomitantly with improvement on serum lipid profile, insulin resistance, and glucose homeostasis. CONCLUSIONS: This study highlights the anti-obesity properties of melanocortins by promoting ingWAT browning and provides new perspectives for future designing of more effective therapeutic strategies.
Assuntos
Adipócitos/metabolismo , Tecido Adiposo Bege/efeitos dos fármacos , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Melanocortinas/farmacologia , Obesidade/prevenção & controle , Termogênese/efeitos dos fármacos , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Tecido Adiposo Bege/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Células Cultivadas , Dieta Hiperlipídica , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Termogênese/fisiologiaRESUMO
Fetal lipomyelomeningocele was suspected during the second-trimester ultrasound and confirmed by magnetic resonance imaging. The pregnancy took its course and a term neonate was delivered. At 2 years of age lipomyelomeningocele surgical removal was performed. The patient is now 4 years old and, despite neurogenic bladder, is a healthy boy with normal psychomotor development for his age. This case illustrates the favorable prognosis of this entity and the importance of prompt diagnosis and multidisciplinary counseling.
Assuntos
Meningomielocele/diagnóstico , Segundo Trimestre da Gravidez , Ultrassonografia Pré-Natal/métodos , Adulto , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Meningomielocele/cirurgia , Defeitos do Tubo Neural/diagnóstico por imagem , GravidezRESUMO
PURPOSE: Autophagy and apoptosis play critical roles in both development and tissue homeostasis in response to (patho)physiological stimuli, such as high-fat diet (HFD) and endurance training (ET). Therefore, we aimed to investigate how ET modulates autophagy and apoptotic-related signaling in visceral adipose tissue of long-standing HFD-fed rats. METHODS: The study was conducted over a 17-week period on Sprague-Dawley rats, which were divided into four groups (n = 8/group): standard diet sedentary (STD+SED), high-fat diet sedentary (HFD+SED), standard diet ET (STD+ET) and high-fat diet ET (HFD+ET). After 9 weeks of dietary regimens, ET groups were trained for 8 weeks on treadmill (5 days/week at 25 m/min for 60 min/day), while maintaining dietary regimens. Autophagy and apoptotic-signaling markers in epididymal white adipose tissue (eWAT) were determined using RT-qPCR, Western blot and spectrometry techniques. RESULTS: ET reduced body weight, visceral fat mass and HOMA-IR in standard and HF diet-fed animals. Moreover, ET reverted the HFD-induced increases in the percentage of larger adipocytes and also reduced the percentage of smaller adipocytes. The HFD decreased pre-adipocyte factor 1 (DLK1/PREF1) and increased the pro-apoptotic markers (Bax protein and caspase 3-like activity), while having no impact on autophagy markers. However, ET increased DLK1/PREF1 and Bcl-2 in both diet types, while decreasing Bax and caspases 9, 8 and 3-like activities in HFD feeding rats. Additionally, Beclin-1 and p62 protein significantly increased in ET groups of both diet types. CONCLUSIONS: Data demonstrate that 8 weeks of ET was effective in attenuating apoptotic-related signaling in long-standing HFD-fed rats. Moreover, HFD and ET had no impact on VAT autophagy markers.
Assuntos
Tecido Adiposo/metabolismo , Autofagia , Dieta Hiperlipídica , Gordura Intra-Abdominal/metabolismo , Condicionamento Físico Animal , Animais , Dieta Hiperlipídica/efeitos adversos , Masculino , Obesidade , Ratos , Ratos Sprague-DawleyRESUMO
The species Phytomonas serpens is known to express some molecules displaying similarity to those described in trypanosomatids pathogenic to humans, such as peptidases from Trypanosoma cruzi (cruzipain) and Leishmania spp. (gp63). In this work, a population of P. serpens resistant to the calpain inhibitor MDL28170 at 70 µ m (MDLR population) was selected by culturing promastigotes in increasing concentrations of the drug. The only relevant ultrastructural difference between wild-type (WT) and MDLR promastigotes was the presence of microvesicles within the flagellar pocket of the latter. MDLR population also showed an increased reactivity to anti-cruzipain antibody as well as a higher papain-like proteolytic activity, while the expression of calpain-like molecules cross-reactive to anti-Dm-calpain (from Drosophila melanogaster) antibody and calcium-dependent cysteine peptidase activity were decreased. Gp63-like molecules also presented a diminished expression in MDLR population, which is probably correlated to the reduction in the parasite adhesion to the salivary glands of the insect vector Oncopeltus fasciatus. A lower accumulation of Rhodamine 123 was detected in MDLR cells when compared with the WT population, a phenotype that was reversed when MDLR cells were treated with cyclosporin A and verapamil. Collectively, our results may help in the understanding of the roles of calpain inhibitors in trypanosomatids.
Assuntos
Inibidores de Cisteína Proteinase/farmacologia , Dipeptídeos/farmacologia , Proteínas de Membrana Transportadoras/efeitos dos fármacos , Peptídeo Hidrolases/efeitos dos fármacos , Trypanosomatina/efeitos dos fármacos , Calpaína/antagonistas & inibidores , Calpaína/química , Calpaína/efeitos dos fármacos , Calpaína/genética , Cisteína Endopeptidases/imunologia , Resistência a Medicamentos , Glicoproteínas/farmacologia , Leishmania/química , Leishmania/fisiologia , Proteínas de Membrana Transportadoras/genética , Peptídeo Hidrolases/genética , Proteínas de Protozoários/imunologia , Trypanosoma cruzi/química , Trypanosoma cruzi/fisiologia , Trypanosomatina/genéticaRESUMO
In cooperative breeders, aggression from dominant breeders directed at subordinates may raise subordinate stress hormone (glucocorticoid) concentrations. This may benefit dominants by suppressing subordinate reproduction but it is uncertain whether aggression from dominants can elevate subordinate cooperative behaviour, or how resulting changes in subordinate glucocorticoid concentrations affect their cooperative behaviour. We show here that the effects of manipulating glucocorticoid concentrations in wild meerkats (Suricata suricatta) on cooperative behaviour varied between cooperative activities as well as between the sexes. Subordinates of both sexes treated with a glucocorticoid receptor antagonist (mifepristone) exhibited significantly more pup protection behaviour (babysitting) compared to those treated with glucocorticoids (cortisol) or controls. Females treated with mifepristone had a higher probability of exhibiting pup food provisioning (pup-feeding) compared to those treated with cortisol. In males, there were no treatment effects on the probability of pup-feeding, but those treated with cortisol gave a higher proportion of the food they found to pups than those treated with mifepristone. Using 19 years of behavioural data, we also show that dominant females did not increase the frequency with which they directed aggression at subordinates at times when the need for assistance was highest. Our results suggest that it is unlikely that dominant females manipulate the cooperative behaviour of subordinates through the effects of aggression on their glucocorticoid levels and that the function of aggression directed at subordinates is probably to reduce the probability they will breed.
Assuntos
Agressão , Comportamento Animal , Comportamento Cooperativo , Glucocorticoides/fisiologia , Herpestidae/fisiologia , Animais , Feminino , Masculino , Mifepristona/administração & dosagem , Receptores de Glucocorticoides/antagonistas & inibidores , Reprodução , Predomínio SocialRESUMO
OBJECTIVE: The purpose of this study was to describe and evaluate the effect of focused process improvements on protocol selection and scheduling in the MRI division of a busy academic medical center, as measured by examination and room times, magnet fill rate, and potential revenue increases and cost savings to the department. MATERIALS AND METHODS: Focused process improvements, led by a multidisciplinary team at a large academic medical center, were directed at streamlining MRI protocols and optimizing matching protocol ordering to scheduling while maintaining or improving image quality. Data were collected before (June 2013) and after (March 2015) implementation of focused process improvements and divided by subspecialty on type of examination, allotted examination time, actual examination time, and MRI parameters. Direct and indirect costs were compiled and analyzed in consultation with the business department. Data were compared with evaluated effects on selected outcome and efficiency measures, as well as revenue and cost considerations. Statistical analysis was performed using a t test. RESULTS: During the month of June 2013, 2145 MRI examinations were performed at our center; 2702 were performed in March 2015. Neuroradiology examinations were the most common (59% in June 2013, 56% in March 2015), followed by body examinations (25% and 27%). All protocols and parameters were analyzed and streamlined for each examination, with slice thickness, TR, and echo train length among the most adjusted parameters. Mean time per examination decreased from 43.4 minutes to 36.7 minutes, and mean room time per patient decreased from 46.3 to 43.6 minutes (p = 0.009). Potential revenue from increased throughput may yield up to $3 million yearly (at $800 net revenue per scan) or produce cost savings if the facility can reduce staffed scanner hours or the number of scanners in its fleet. Actual revenue and expense impacts depend on the facility's fixed and variable cost structure, payer contracts, MRI fleet composition, and unmet MRI demand. CONCLUSION: Focused process improvements in selecting MRI protocols and scheduling examinations significantly increased throughput in the MRI division, thereby increasing capacity and revenue. Shorter scan and department times may also improve patient experience.
Assuntos
Centros Médicos Acadêmicos/economia , Eficiência Organizacional/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Avaliação de Processos em Cuidados de Saúde/economia , Melhoria de Qualidade/economia , Serviço Hospitalar de Radiologia/economia , Centros Médicos Acadêmicos/estatística & dados numéricos , Boston/epidemiologia , Humanos , Serviço Hospitalar de Radiologia/estatística & dados numéricos , Carga de Trabalho/economia , Carga de Trabalho/estatística & dados numéricosRESUMO
OBJECTIVE: The objective of this study is to optimize MRI logistics through evaluation of MRI workflow and analysis of performance, efficiency, and patient throughput in a tertiary care academic center. SUBJECTS AND METHODS: For 2 weeks, workflow data from two outpatient MRI scanners were prospectively collected and stratified by value added to the process (i.e., value-added time, business value-added time, or non-value-added time). Two separate time cycles were measured: the actual MRI process cycle as well as the complete length of patient stay in the department. In addition, the impact and frequency of delays across all observations were measured. RESULTS: A total of 305 MRI examinations were evaluated, including body (34.1%), neurologic (28.9%), musculoskeletal (21.0%), and breast examinations (16.1%). The MRI process cycle lasted a mean of 50.97 ± 24.4 (SD) minutes per examination; the mean non-value-added time was 13.21 ± 18.77 minutes (25.87% of the total process cycle time). The mean length-of-stay cycle was 83.51 ± 33.63 minutes; the mean non-value-added time was 24.33 ± 24.84 minutes (29.14% of the total patient stay). The delay with the highest frequency (5.57%) was IV or port placement, which had a mean delay of 22.82 minutes. The delay with the greatest impact on time was MRI arthrography for which joint injection of contrast medium was necessary but was not accounted for in the schedule (mean delay, 42.2 minutes; frequency, 1.64%). Of 305 patients, 34 (11.15%) did not arrive at or before their scheduled time. CONCLUSION: Non-value-added time represents approximately one-third of the total MRI process cycle and patient length of stay. Identifying specific delays may expedite the application of targeted improvement strategies, potentially increasing revenue, efficiency, and overall patient satisfaction.
Assuntos
Eficiência , Imageamento por Ressonância Magnética/estatística & dados numéricos , Pacientes/estatística & dados numéricos , Desempenho Profissional , Fluxo de Trabalho , Humanos , Estudos Prospectivos , Registros , Centros de Atenção TerciáriaRESUMO
We aimed to investigate the effects of two physical exercise models, voluntary physical activity (VPA) and endurance training (ET) as preventive and therapeutic strategies, respectively, on lipid accumulation regulators and mitochondrial content in VAT of rats fed a high-fat diet (HFD). Sprague-Dawley rats (6 weeks old, n=60) were assigned into sedentary and VPA groups fed isoenergetic diets: standard (S, 35 kcal% fat) or HFD (71 kcal% fat). The VPA groups had free access to wheel running during the entire protocol. After 9 weeks, half of the sedentary animals were exercised on a treadmill while maintaining the dietary treatments. The HFD induced no changes in plasma non-esterified fatty acids (NEFA) and glycerol levels and decreased oxidative phosphorylation (OXPHOS) subunit IV and increased truncated/full-length sterol regulatory element-binding transcription factor 1c (SREBP1c) ratio in epididymal white adipose tissue (eWAT). VPA decreased plasma glycerol levels, aquaglyceroporin 7 (AQP7) and increased subunit I of cytochrome c oxidase (COX) protein, in standard diet fed animals. Eight weeks of ET decreased body weight, visceral adiposity and adipocyte size and plasma NEFA and glycerol levels, as well as AQP7 protein expression in eWAT. ET increased fatty acid translocase (FAT/CD36), mitochondrial content of complexes IV and V subunits, mitochondrial biogenesis and dynamic (mitofusins and optic atrophy 1)-related proteins. Moreover, lipogenesis-related markers (SREBP1c and acetyl CoA carboxylase) were reduced after 8 weeks of ET. In conclusion, ET-induced alterations reflect a positive effect on mitochondrial function and the overall VAT metabolism of HFD-induced obese rats.