Plano de Negócios: Turismo em espaço rural na Serra de Tomar

O Plano de Negócios que se apresenta tem como principal objetivo a implementação e exploração de uma unidade de Casas de Campo – as “Casas de Santa Iria” – na região de Tomar. Sendo o Turismo sector fundamental para o desenvolvimento económico de um país, é pretendido através desta unidade de Turismo em Espaço Rural, estimular o desenvolvimento turístico da região, combatendo o abandono e a sazonalidade verificados nesta zona centro de Portugal. Através deste projeto empreendedor, que consiste na reabilitação casas rurais para utilização turística, é aspirado demonstrar o verdadeiro significado de ambiente rural em plena harmonia com a natureza, através da hospitalidade tipicamente portuguesa e atividades complementares oferecidas pelo estabelecimento de Turismo em Espaço Rural “Casas de Santa Iria”. Considerando o total de investimentos na ordem dos 220 mil euros, os fluxos de caixa previsionais e o custo de oportunidade do capital, o projeto apresenta um VAL de 913.749€, uma TIR de 57,41%% e um pay back period de quatro anos, critérios que garantem a sua viabilidade económico-financeira.The business plan here presented aims to implement a project of countryside houses, called "Casas de Santa Iria", in the Centro region of Portugal, Tomar Tourism emerges as a key sector for economic development of a country, so for is intended through the implementation of this unit of rural tourism, stimulate tourism development in the region, fighting abandonment and seasonality verified in this area. Through this entrepreneurial project, which consists in the rehabilitation of rural houses for tourist purpose, is drawn to show the true meaning of rural environment in harmony with nature, through the typical portuguese hospitality and complementary activities offered by the rural tourism unit "Casas de Santa Iria". Considering the total investment of 220 thousand euros, the forecast cash flows and the opportunity cost of capital, the project has an NPV of € 913,749, an IRR of 57.41% and a payback period of four years, criteria which ensures the project viability

A historical cohort study

OK Funding Information: Catarina R. Palma dos Reis acknowledges support from a Clarendon Fund Scholarship. Publisher Copyright: © 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).Introduction: The velocity of fetal deterioration in fetal growth restriction is extremely variable, which makes monitoring and counseling very challenging. The soluble fms-like tyrosine kinase to placental growth factor (sFlt1/PlGF) ratio provides a readout of the vasoactive environment that correlates with preeclampsia and fetal growth restriction and that could be useful to predict fetal deterioration. Previous studies showed a correlation between higher sFlt1/PlGF ratios and lower gestational ages at birth, although it is unclear whether this is due to the increased incidence of preeclampsia. Our goal was to evaluate whether the sFlt1/PlGF ratio predicts faster fetal deterioration in early fetal growth restriction. Material and methods: This was a historical cohort study in a tertiary maternity hospital. Data from singleton pregnancies with early fetal growth restriction (diagnosed before 32 gestational weeks) confirmed after birth monitored between January 2016 and December 2020 were retrieved from clinical files. Cases of chromosomal/fetal abnormalities, infection and medical terminations of pregnancy were excluded. The sFlt1/PlGF ratio was acquired at diagnosis of early fetal growth restriction in our unit. The correlation of log10 sFlt1/PlGF with latency to delivery/fetal demise was assessed with linear, logistic (positive sFlt1/PlGF if >85) and Cox regression excluding deliveries for maternal conditions and controlling for preeclampsia, gestational age at time of ratio test, maternal age and smoking during pregnancy. Receiver-operating characteristic (ROC) analysis tested the performance of sFlt1/PlGF ratio in predicting delivery for fetal reasons in the following week. Results: 125 patients were included. Mean sFlt1/PlGF ratio was 91.2 (SD 148.7) and 28% of patients had a positive ratio. A higher log10 sFlt1/PlGF ratio predicted shorter latency for delivery/fetal demise in linear regression after controlling for confounders, β = −3.001, (−3.713 to −2.288). Logistic regression with ratio positivity confirmed these findings (latency for delivery 5.7 ± 3.32 weeks for ratios ≤85 vs 1.9 ± 1.52 weeks for ratios >85); β = −0.698 (−1.064 to −0.332). Adjusted Cox regression showed that a positive ratio confers a significantly positive hazard ratio (HR) for earlier delivery/fetal demise, HR 9.869 (5.061–19.243). ROC analysis showed an area under the curve of 0.847 (SE ± 0.06). Conclusions: sFlt1/PlGF ratio is correlated with faster fetal deterioration in early fetal growth restriction, independently of preeclampsia.publishersversionepub_ahead_of_prin

Plasma Concentrations of Soluble Endoglin versus Standard Evaluation in Patients with Suspected Preeclampsia

Background: The purpose of this study was to compare plasma soluble endoglin (sEng) levels with standard clinical evaluation or plasma levels of other angiogenic proteins [soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF)] in predicting short-term adverse maternal and perinatal outcomes in women with suspected preeclampsia presenting prior to 34 weeks. Methods and Findings: Data from all women presenting at <34 weeks for evaluation of preeclampsia with singleton pregnancies (July 2009−October 2010) were included in this analysis and sEng levels were measured at presentation. Data was analyzed for 170 triage encounters and presented as median {25−75th centile}. Thirty-three percent of patients (56 of 170) experienced an adverse outcome. sEng levels (ng/ml) were significantly elevated in patients who subsequently experienced adverse outcomes compared to those who did not (32.3 {18.1, 55.8} vs 4.8 {3.2, 8.6}, p<0.0001). At a 10% false positive rate, sEng had higher detection rates of adverse outcomes than the combination of highest systolic blood pressure, proteinuria and abnormal laboratory tests (80.4 {70.0, 90.8} vs 63.8 {51.4, 76.2}, respectively). Subjects in the highest quartile of sEng were more likely to deliver early compared to those in the lowest quartile (HR: 14.96 95% CI: 8.73−25.62, p<0.0001). Natural log transformed sEng correlated positively with log sFlt1 levels (r = 0.87) and inversely with log PlGF levels (r = −0.79) (p<0.0001 for both). Plasma sEng had comparable area under the curve for prediction of adverse outcomes as measurement of sFlt1/PlGF ratio (0.88 {0.81, 0.95} for sEng versus 0.89 {0.83, 0.95} for sFlt1/PlGF ratio, p = 0.74). Conclusions: In women with suspected preeclampsia presenting prior to 34 weeks of gestation, sEng performs better than standard clinical evaluation in detecting adverse maternal and fetal outcomes occurring within two weeks of presentation. Soluble endoglin was strongly correlated with sFlt1 and PlGF levels, suggesting common pathogenic pathways leading to preeclampsia

Lipidomic Assessment of Plasma and Placenta of Women with Early-Onset Preeclampsia

Introduction: Adipose tissue is responsible for triggering chronic systemic inflammatory response and these changes may be involved in the pathophysiology of preeclampsia. Objective: To characterize the lipid profile in the placenta and plasma of patients with preeclampsia. Methodology Samples were collected from placenta and plasma of 10 pregnant women with preeclampsia and 10 controls. Lipids were extracted using the Bligh–Dyer protocol and were analysed by MALDI TOF-TOF mass spectrometry. Results: Approximately 200 lipid signals were quantified. The most prevalent lipid present in plasma of patients with preeclampsia was the main class Glycerophosphoserines-GP03 (PS) representing 52.30% of the total lipid composition, followed by the main classes Glycerophosphoethanolamines-GP02 (PEt), Glycerophosphocholines-GP01 (PC) and Flavanoids-PK12 (FLV), with 24.03%, 9.47% and 8.39% respectively. When compared to the control group, plasma samples of patients with preeclampsia showed an increase of PS (p<0.0001), PC (p<0.0001) and FLV (p<0.0001). Placental analysis of patients with preeclampsia, revealed the PS as the most prevalent lipid representing 56.28%, followed by the main class Macrolides/polyketides-PK04 with 32.77%, both with increased levels when compared with patients control group, PS (p<0.0001) and PK04 (p<0.0001). Conclusion: Lipids found in placenta and plasma from patients with preeclampsia differ from those of pregnant women in the control group. Further studies are needed to clarify if these changes are specific and a cause or consequence of preeclampsia

Placental extracellular vesicles express active dipeptidyl peptidase IV; levels are increased in gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy and is characterized by insulin resistance and decreased circulating glucagon-like peptide-1 (GLP-1). GDM resolves rapidly after delivery implicating the placenta in the disease. This study examines the biological functions that cause this pathology. The placenta releases syncytiotrophoblast-derived extracellular vesicles (STB-EVs) into the maternal circulation, which is enhanced in GDM. Dipeptidyl peptidase IV (DPPIV) is known to play a role in type 2 diabetes by breaking down GLP-1, which in turn regulates glucose-dependent insulin secretion. STB-EVs from control and GDM women were analysed. We show that normal human placenta releases DPPIV-positive STB-EVs and that they are higher in uterine than paired peripheral blood, confirming placental origin. DPPIV-bound STB-EVs from normal perfused placentae are dose dependently inhibited with vildagliptin. DPPIV-bound STB-EVs from perfused placentae are able to breakdown GLP-1 . STB-EVs from GDM perfused placentae show greater DPPIV activity. Importantly, DPPIV-bound STB-EVs increase eightfold in the circulation of women with GDM. This is the first report of STB-EVs carrying a biologically active molecule that has the potential to regulate maternal insulin secretion

A cross-sectional analysis of syncytiotrophoblast membrane extracellular vesicles–derived transcriptomic biomarkers in early-onset preeclampsia

BackgroundPreeclampsia (PE) is a pregnancy-specific hypertensive disorder affecting 2%–8% of pregnancies worldwide. Biomarker(s) for the disorder exists, but while these have excellent negative predictive value, their positive predictive value is poor. Extracellular vesicles released by the placenta into the maternal circulation, syncytiotrophoblast membrane extracellular vesicles (STB-EVs), have been identified as being involved in PE with the potential to act as liquid biopsies.ObjectiveThe objective of this study was to identify the difference in the transcriptome of placenta and STB-EVs between preeclampsia and normal pregnancy (NP) and mechanistic pathways.Methods/study designWe performed RNA-sequencing on placental tissue, medium/large and small STB-EVs from PE (n = 6) and NP (n = 6), followed by bioinformatic analysis to identify targets that could be used in the future for EV-based diagnostic tests for preeclampsia. Some of the identified biomarkers were validated with real-time polymerase chain reactions.ResultsOur analysis identified a difference in the transcriptomic STB-EV cargo between PE and NP. We then identified and verified the differential expression of FLNB, COL17A1, SLC45A4, LEP, HTRA4, PAPP-A2, EBI3, HSD17B1, FSTL3, INHBA, SIGLEC6, and CGB3. Our analysis also identified interesting mechanistic processes via an in silico prediction of STB-EV-based mechanistic pathways.ConclusionsIn this study, using comprehensive profiling of differentially expressed/carried genes of three linked sample subtypes in PE, we identified potential biomarkers and mechanistic gene pathways that may be important in the pathophysiology of PE and could be further explored in future studies

Modeling risk for severe adverse outcomes using angiogenic factor measurements in women with suspected preterm preeclampsia

Introduction: Preeclampsia (PE) is a pregnancy-specific syndrome associated with adverse maternal and fetal outcomes. Patient-specific risks based on angiogenic factors might better categorize those who might have a severe adverse outcome. Methods: Women evaluated for suspected PE at a tertiary hospital (2009–2012) had pregnancy outcomes categorized as ‘referent’ or ‘severe’, based solely on maternal/fetal findings. Outcomes that may have been influenced by a PE diagnosis were considered ‘unclassified’. Soluble fms-like tyrosine kinase (sFlt1) and placental growth factor (PlGF) were subjected to bivariate discriminant modeling, allowing patient-specific risks to be assigned for severe outcomes. Results: Three hundred twenty-eight singleton pregnancies presented at ≤34.0 weeks' gestation. sFlt1 and PlGF levels were adjusted for gestational age. Risks above 5 : 1 (10-fold over background) occurred in 77% of severe (95% CI 66 to 87%) and 0.7% of referent (95% CI <0.1 to 3.8%) outcomes. Positive likelihood ratios for the modeling and validation datasets were 19 (95% CI 6.2–58) and 15 (95% CI 5.8–40) fold, respectively. Conclusions: This validated model assigns patient-specific risks of any severe outcome among women attending PE triage. In practice, women with high risks would receive close surveillance with the added potential for reducing unnecessary preterm deliveries among remaining women. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd

The diversity and evolution of pollination systems in large plant clades: Apocynaceae as a case study

Background and Aims Large clades of angiosperms are often characterized by diverse interactions with pollinators, but how these pollination systems are structured phylogenetically and biogeographically is still uncertain for most families. Apocynaceae is a clade of >5300 species with a worldwide distribution. A database representing >10 % of species in the family was used to explore the diversity of pollinators and evolutionary shifts in pollination systems across major clades and regions. Methods The database was compiled from published and unpublished reports. Plants were categorized into broad pollination systems and then subdivided to include bimodal systems. These were mapped against the five major divisions of the family, and against the smaller clades. Finally, pollination systems were mapped onto a phylogenetic reconstruction that included those species for which sequence data are available, and transition rates between pollination systems were calculated. Key Results Most Apocynaceae are insect pollinated with few records of bird pollination. Almost three-quarters of species are pollinated by a single higher taxon (e.g. flies or moths); 7 % have bimodal pollination systems, whilst the remaining approx. 20 % are insect generalists. The less phenotypically specialized flowers of the Rauvolfioids are pollinated by a more restricted set of pollinators than are more complex flowers within the Apocynoids + Periplocoideae + Secamonoideae + Asclepiadoideae (APSA) clade. Certain combinations of bimodal pollination systems are more common than others. Some pollination systems are missing from particular regions, whilst others are over-represented. Conclusions Within Apocynaceae, interactions with pollinators are highly structured both phylogenetically and biogeographically. Variation in transition rates between pollination systems suggest constraints on their evolution, whereas regional differences point to environmental effects such as filtering of certain pollinators from habitats. This is the most extensive analysis of its type so far attempted and gives important insights into the diversity and evolution of pollination systems in large clades

Cistite idiopática felina e o aporte nutricional: uma dualidade a considerar

Dissertação de Mestrado Integrado em Medicina VeterináriaA cistite idiopática felina (CIF) é a causa mais comum da doença do trato urinário inferior felino (DTUIF), a qual constitui um importante problema na medicina felina. Apesar dos inúmeros estudos efetuados, a etiopatogenia da CIF não é totalmente conhecida, pelo que ainda não existe um tratamento padrão amplamente aceite e eficaz no controlo das recorrências desta doença. Neste estudo, o qual decorreu entre 1 de janeiro de 2015 e 31 de julho de 2016 pretendeu-se efetuar uma revisão bibliográfica da CIF, bem como a caraterização epidemiológica e clínica dos gatos com CIF. Durante este período foram analisados 40 gatos com DTUIF. Destes, 26 (65%) apresentavam CIF, 6 (15%) tampão uretral, 5 (12%) urolitíase, 2 (5%) infeção do trato urinário (ITU) e 1 (3%) atonia vesical. Para efetuar a caraterização epidemiológica e clínica dos gatos com CIF (grupo-alvo), recolheu-se a informação relativa à raça, idade, género, estado reprodutivo, peso, condição corporal, temperamento, estilo de vida, convívio com outros animais, tipo de dieta, exposição a fatores de stresse, época sazonal do aparecimento dos sinais clínicos, historial clínico da doença, sinais clínicos, resultados dos exames complementares de diagnóstico, diagnóstico final, tratamento prescrito e evolução clínica de cada caso. Os resultados desta análise encontram-se de acordo com o descrito em vários estudos, à exceção do temperamento dos gatos, pois neste estudo, contrariamente ao descrito, verificou-se uma percentagem elevada de gatos meigos. Do total da amostra de gatos com CIF (26 gatos), a 10 (38%) institui-se um tratamento nutricional com uma ração terapêutica (Hill’s c/d Feline Urinary Stress), 2 (20%) destes gatos apresentaram recorrência da doença. A 8 (31%) gatos recomendou-se um tratamento médico com amitriptilina, dos quais 2 (25%) recidivaram. A 5 (19%) gatos prescreveu-se um tratamento nutricional com uma ração terapêutica (Hill’s c/d Feline Urinary Stress) e um suplemento nutricional (Cystaid Plus). Destes, 2 (40%) gatos apresentaram um novo episódio da CIF e a 3 (12%) gatos, institui-se um tratamento com o suplemento nutricional (Calmurofel), dos quais 1 (33%) recidivou. A análise dos resultados parece indicar que a ração Hill’s c/d Feline Urinary Stress e o suplemento Calmurofel apresentam um efeito positivo no controlo da CIF. No entanto serão necessários estudos randomizados com um maior número de casos para clarificar os nossos resultados.Feline idiopathic cystitis (FIC) is the most common cause of feline lower urinary tract disease (FLUTD), which is a major problem in feline medicine. Despite many studies performed, the etiopathogenesis of FIC is still not fully known and there’s still no widely accepted and effective standard treatment in controlling recurrences of this disease. In this study, which took place between 1 January 2015 and 31 July 2016, was performed a intented to make a literature review of FIC, as well as epidemiological and clinical characterization of the cats with FIC. During this period, 40 cats with FLUTD were analysed. Of these, 26 (65%) were diagnosed with FIC, 6 (15%) with urethral plugs, 5 (12%) with urolithiasis, 2 (5%) with urinary tract infection and 1 (3%) with atonic bladder. For epidemiological and clinical characterization of cats with FIC (target group), information concerning breed, age, gender, reproductive status, weight, body condition, temper, lifestyle, living with others animals, type of diet, exposure to stressors, seasonal time of onset of clinical signs, clinical history of disease, clinical signs, results of diagnostic tests, prescribed treatment, diagnosis and clinical evolution of each cat, it was collected. The results of this analysis are in accordance with described in several studies, except for temper of the cats. Opposed to the described on the literature, a high percentage of kind cats was found in the present study. From the total sample of cats with FIC (26 cats), a nutritional treatment with therapeutic food (Hill’s c/d Feline urinary stress) was instituted in 10 (38%) cats of which 2 (20%) had recurrence of disease. A medical treatment with amitriptyline was recommended in 8 (31%) cats of which 2 (25%) relapsed. A nutritional treatment with therapeutic food (Hill’s c/d Feline urinary stress) and a nutritional supplement (Cystaid Plus) was prescribed in 5 (19%) cats. Of these, 2 (40%) had a new episode of FIC and a treatment with nutritional supplement (calmurofel) was instituted in 3 (12%) cats of which 1 (33%) relapsed. The analysis of the results seems to indicate that the therapeutic food Hill’s c/d Feline Urinary Stress and the nutritional supplement Calmurofel might have a positive effect on FIC control. However randomized studies will be necessary to confirm our results