Carbon sequestration scenarios in Portugal: which way to go forward?

Assessing carbon storage and sequestration is key for defining effective conservation actions to mitigate climate change. Forest species changes have direct impacts on carbon stocks and may lead to undesirable climate trade-offs. In this paper, we measure aboveground biomass (AGB) and the impact of forest changes on climate regulation through three land policy scenarios by 2030 in continental Portugal. We found that a High intervention scenario, supported by an important increase in "Other coniferous trees" class, will provide 29.5% more of carbon sequestration, whereas a Low intervention scenario, in which there is a moderate increase in all forest classes, will result in an increase of 5.7%. A business as usual (BAU) scenario, supported by an increase in eucalyptus forests and a decrease in autochthonous species, will decrease carbon sequestration (-2.7%), particularly Lisboa, Algarve and North regions. Economic valuation shows that the High intervention scenario will generate the highest economic outcome for climate regulation by 2030. This study provides a spatial-based methodology for monitoring carbon sequestration and new insights about the impact of policies for Green House Gas (GHG) mitigation, supporting the 2030 Sustainable Development Goals achievement.

Trends in pediatric epilepsy surgery in Europe between 2008 and 2015: Country-, center-, and age-specific variation.

OBJECTIVE: To profile European trends in pediatric epilepsy surgery (<16 years of age) between 2008 and 2015. METHODS: We collected information on volumes and types of surgery, pathology, and seizure outcome from 20 recognized epilepsy surgery reference centers in 10 European countries. RESULTS: We analyzed retrospective aggregate data on 1859 operations. The proportion of surgeries significantly increased over time (P < .0001). Engel class I outcome was achieved in 69.3% of children, with no significant improvement between 2008 and 2015. The proportion of histopathological findings consistent with glial scars significantly increased between the ages of 7 and 16 years (P for trend = .0033), whereas that of the remaining pathologies did not vary across ages. A significant increase in unilobar extratemporal surgeries (P for trend = .0047) and a significant decrease in unilobar temporal surgeries (P for trend = .0030) were observed between 2008 and 2015. Conversely, the proportion of multilobar surgeries and unrevealing magnetic resonance imaging cases remained unchanged. Invasive investigations significantly increased, especially stereo-electroencephalography. We found different trends comparing centers starting their activity in the 1990s to those whose programs were developed in the past decade. Multivariate analysis revealed a significant variability of the proportion of the different pathologies and surgical approaches across countries, centers, and age groups between 2008 and 2015. SIGNIFICANCE: Between 2008 and 2015, we observed a significant increase in the volume of pediatric epilepsy surgeries, stability in the proportion of Engel class I outcomes, and a modest increment in complexity of the procedures.

Remotely Sensed Data Fusion for Spatiotemporal Geostatistical Analysis of Forest Fire Hazard.

Forest fires are a natural phenomenon which might have severe implications on natural and anthropogenic ecosystems. Future projections predict that, under a climate change environment, the fire season would be lengthier with higher levels of droughts, leading to higher fire severity. The main aim of this paper is to perform a spatiotemporal analysis and explore the variability of fire hazard in a small Greek island, Skiathos (a prototype case of fragile environment) where the land uses mixture is very high. First, a comparative assessment of two robust modeling techniques was examined, namely, the Analytical Hierarchy Process (AHP) knowledge-based and the fuzzy logic AHP to estimate the fire hazard in a timeframe of 20 years (1996-2016). The former technique was proven more representative after the comparative assessment with the real fire perimeters recorded on the island (1984-2016). Next, we explored the spatiotemporal dynamics of fire hazard, highlighting the risk changes in space and time through the individual and collective contribution of the most significant factors (topography, vegetation features, anthropogenic influence). The fire hazard changes were not dramatic, however, some changes have been observed in the southwestern and northern part of the island. The geostatistical analysis revealed a significant clustering process of high-risk values in the southwestern and northern part of the study area, whereas some clusters of low-risk values have been located in the northern territory. The degree of spatial autocorrelation tends to be greater for 1996 rather than for 2016, indicating the potential higher transmission of fires at the most susceptible regions in the past. The knowledge of long-term fire hazard dynamics, based on multiple types of remotely sensed data, may provide the fire and land managers with valuable fire prevention and land use planning tools.

Searching for Networks: Ecological Connectivity for Amphibians Under Climate Change.

Ecological connectivity depends on key elements within the landscape, which can support ecological fluxes, species richness and long-term viability of a biological community. Landscape planning requires clear aims and quantitative approaches to identify which key elements can reinforce the spatial coherence of protected areas design. We aim to explore the probability of the ecological connectivity of forest remnants and amphibian species distributions for current and future climate scenarios across the Central Corridor of the Brazilian Atlantic Forest. Integrating amphibian conservation, climate change and ecological corridors, we design a landscape ranking based on graph and circuit theories. To identify the sensitivity of connected areas to climate-dependent changes, we use the Model for Interdisciplinary Research on Climate by means of simulations for 2080-2100, representing a moderated emission scenario within an optimistic context. Our findings indicate that more than 70% of forest connectivity loss by climate change may drastically reduce amphibian dispersal in this region. We show that high amphibian turnover rates tend to be greater in the north-eastern edges of the corridor across ensembles of forecasts. Our spatial analysis reveals a general pattern of low-conductance areas in landscape surface, yet with some well-connected patches suggesting potential ecological corridors. Atlantic Forest reserves are expected to be less effective in a near future. For improved conservation outcomes, we recommend some landscape paths with low resistance values across space and time. We highlight the importance of maintaining forest remnants in the southern Bahia region by drafting a blueprint for functional biodiversity corridors.

Identification of novel genetic causes of Rett syndrome-like phenotypes.

BACKGROUND: The aim of this work was to identify new genetic causes of Rett-like phenotypes using array comparative genomic hybridisation and a whole exome sequencing approach. METHODS AND RESULTS: We studied a cohort of 19 Portuguese patients (16 girls, 3 boys) with a clinical presentation significantly overlapping Rett syndrome (RTT). Genetic analysis included filtering of the single nucleotide variants and indels with preference for de novo, homozygous/compound heterozygous, or maternally inherited X linked variants. Examination by MRI and muscle biopsies was also performed. Pathogenic genomic imbalances were found in two patients (10.5%): an 18q21.2 deletion encompassing four exons of the TCF4 gene and a mosaic UPD of chromosome 3. Variants in genes previously implicated in neurodevelopmental disorders (NDD) were identified in six patients (32%): de novo variants in EEF1A2, STXBP1 and ZNF238 were found in three patients, maternally inherited X linked variants in SLC35A2, ZFX and SHROOM4 were detected in two male patients and one homozygous variant in EIF2B2 was detected in one patient. Variants were also detected in five novel NDD candidate genes (26%): we identified de novo variants in the RHOBTB2, SMARCA1 and GABBR2 genes; a homozygous variant in EIF4G1; compound heterozygous variant in HTT. CONCLUSIONS: Network analysis reveals that these genes interact by means of protein interactions with each other and with the known RTT genes. These findings expand the phenotypical spectrum of previously known NDD genes to encompass RTT-like clinical presentations and identify new candidate genes for RTT-like phenotypes.

Geographic accessibility to primary healthcare centers in Mozambique.

BACKGROUND: Access to healthcare services has an essential role in promoting health equity and quality of life. Knowing where the places are and how much of the population is covered by the existing healthcare network is important information that can be extracted from Geographical Information Systems (GIS) and used in effective healthcare planning. The aim of this study is to measure the geographic accessibility of population to existing Healthcare Centers (HC), and to estimate the number of persons served by the health network of Mozambique. METHODS: Health facilities' locations together with population, elevation, and ancillary data were used to model accessibility to HC using GIS. Two travel time scenarios used by population to attend HC were considered: (1) Driving and; and (2) Walking. Estimates of the number of villages and people located in the region served, i.e. within 60 min from an HC, and underserved area, i.e. outside 60 min from an HC, are provided at national and province level. RESULTS: The findings from this study highlight accessibility problems, especially in the walking scenario, in which 90.2 % of Mozambique was considered an underserved area. In this scenario, Maputo City (69.8 %) is the province with the greatest coverage of HC. On the other hand, Tete (93.4 %), Cabo Delgado (93 %) and Gaza (92.8 %) are the provinces with the most underserved areas. The driving scenario was less problematic, with about 66.9 % of Mozambique being considered a served area. We also found considerable regional disparities at the province level for this scenario, ranging from 100 % coverage in Maputo City to 48.3 % in Cabo Delgado. In terms of population coverage we found that the problem of accessibility is more acute in the walking scenario, in which about 67.3 % of the Mozambican population is located in underserved areas. For the driving scenario, only 6 % of population is located in underserved areas. CONCLUSIONS: This study highlights critical areas in Mozambique in which HC are lacking when assessed by walking and driving travel time distance. The majority of Mozambicans are located in underserved areas in the walking scenario. The mapped outputs may have policy implications and can be used for future decision making processes and analysis. TRIAL REGISTRATION: Not applicable.

Correlation of morphologic and pathologic features of the various tendon groups around the ankle: MR imaging investigation.

OBJECTIVE: To determine if a statistical association exists between abnormalities in one ankle tendon group (i.e., peroneal, medial flexor, or Achilles) and those in another. MATERIALS AND METHODS: A retrospective analysis of 1.5-T and 3-T MR ankle examinations in 100 patients conducted between November 1, 2011 and April 1, 2012 was performed. The cross-sectional areas and diameters of the ankle tendons-Achilles (ACH), peroneus brevis (PB) and longus (PL), tibialis posterior (TP), flexor digitorum longus (FDL), and flexor hallux longus (FHL)-were measured, and the results were correlated to determine any association with the presence of qualitative abnormalities (tenosynovitis, tendinosis, and tendon tearing). RESULTS: Subjects with larger diameters of the ACH tendon also revealed larger PL, TP, FDL, and FHL tendon diameters and sectional areas. Furthermore, subjects with larger PL tendons generally revealed larger flexor tendons and the same was also true when medial compartment tendons were individually assessed and measurements compared among the three of them. There was a statistically significant association with regard to the presence of tendon abnormalities (tendinosis, tenosynovitis, and tearing) in both the peroneal and medial flexor tendons. The presence of an abnormality in the ACH tendon correlated strongly with increasing diameters and areas of all the other ankle tendons except for the PB tendon. CONCLUSIONS: There is an association between quantitative and qualitative abnormalities of one group of tendons when compared with the others with respect to the ACH, medial flexor, and peroneal tendons of the ankle, which is perhaps explained by a retinacular and fascial complex that anatomically connects the three groups.

Study of testosterone as a predictor of tumor aggressiveness in patients with prostate cancer.

PURPOSE: A growing body of evidence suggests that low testosterone can be an independent predictor of adverse clinicopathological features and worse prognosis in prostate cancer (PCa) patients. However, this association is still incompletely understood and the results are divisive. The aim of this study was to analyze testosterone as a predictor of aggressive disease in subjects with clinically localized PCa. MATERIALS AND METHODS: A cohort was conducted including the patients submitted to radical prostatectomy in our institution during a period of four years. The patients had clinically localized disease and their total testosterone (TT) was routinely measured preoperatively in the morning before surgery. They were stratified in groups with low (< 300 ng/dL) and normal TT (≥ 300 ng/dL). Tumor aggressiveness was inferred based on preoperative PSA levels, pathological Gleason score (lower, equal or greater than 7), TNM stage and surgical margins status. RESULTS: After analyzing 164 patients we found a significant association between mean preoperative TT and extraprostatic disease (379 for pT3 vs. 421 ng/for pT2 - p < 0.001, AUC > 0.99). Conversely, men with high Gleason score had similar mean TT compared to those with lower scores. Preoperative low TT (defined as TT < 300 ng/dL) could not be statistically correlated with either preoperative PSA levels, pathological Gleason score, extraprostatic extension, positive surgical margins or seminal vesicles involvement. CONCLUSIONS: This study indicates that testosterone may be a useful predictive tool once pathological extraprostatic extension was somewhat signaled by lower TT levels preoperatively. However, it does not consolidate a clear association between aggressive tumor biology and hypogonadism.

Global conservation prioritization areas in three dimensions of crocodilian diversity.

Crocodilians are a taxonomic group of large predators with important ecological and evolutionary benefits for ecosystem functioning in the face of global change. Anthropogenic actions affect negatively crocodilians' survival and more than half of the species are threatened with extinction worldwide. Here, we map and explore three dimensions of crocodilian diversity on a global scale. To highlight the ecological importance of crocodilians, we correlate the spatial distribution of species with the ecosystem services of nutrient retention in the world. We calculate the effectiveness of global protected networks in safeguarding crocodilian species and provide three prioritization models for conservation planning. Our results show the main hotspots of ecological and evolutionary values are in southern North, Central and South America, west-central Africa, northeastern India, and southeastern Asia. African species have the highest correlation to nutrient retention patterns. Twenty-five percent of the world's crocodilian species are not significantly represented in the existing protected area networks. The most alarming cases are reported in northeastern India, eastern China, and west-central Africa, which include threatened species with low or non-significant representation in the protected area networks. Our highest conservation prioritization model targets southern North America, east-central Central America, northern South America, west-central Africa, northeastern India, eastern China, southern Laos, Cambodia, and some points in southeastern Asia. Our research provides a global prioritization scheme to protect multiple dimensions of crocodilian diversity for achieving effective conservation outcomes.

Rutin ameliorates nitrergic and endothelial dysfunction on vessels and corpora cavernosa of diabetic animals.

Endothelial dysfunction is an early complication of diabetes and it is related to both micro- and macroangiopathies. In addition, >70% of diabetic patients develop autonomic neuropathies. Increased oxidative stress has a major role in the development of both nitrergic and endothelial dysfunction. The aim of this work is to evaluate whether rutin, a potent antioxidant, could ameliorate nitrergic and/or endothelial dysfunction in diabetic animals. Primary and secondary treatment protocols with rutin were investigated on rat aortic rings and the mesenteric arteriolar bed, and on rabbit aortic rings and corpora cavernosa (RbCC) from both euglycemic and alloxan-diabetic animals. Acetylcholine endothelium-dependent and sodium nitroprusside endothelium-independent relaxations were compared in tissues from euglycemic or diabetic animals. Electrical field stimulation (EFS)-induced relaxation was performed only in the RbCC. Endothelial-dependent relaxations were blunted by 40% in vessels and neuronal relaxation was blunted by 50% in RbCC taken from diabetic animals when compared to euglycemic animals. Pre-treatment with rutin restored both neuronal and endothelial dependent relaxations in diabetic animals towards the values achieved in control euglycemic tissues. Rutin was able to ameliorate both endothelial dysfunction and nitrergic neuropathy in animal experimental models. Rutin could be a lead compound in the primary or secondary preventive ancillary treatment of endothelial and nitrergic dysfunction in the course of diabetes.

Prognostic value of urethral mobility and valsalva leak point pressure for female transobturator sling procedure.

PURPOSE: To analyze the influence of urethral mobility and Valsalva leak point pressure on postoperative outcomes of transobturator sling (TOT) for female stress urinary incontinence. MATERIALS AND METHODS: A prospective cohort was conducted including 66 patients submitted to TOT from March 2006 to May 2009. Urethral hypermobility was defined as mobility ≥ 30° on Q-tip test, and Valsalva leak point pressure (VLPP) was classified as greater than 60 cmH2O or 60 and less on preoperative urodynamics. These parameters were compared through well defined postoperative objective and subjective success criteria. Intensity of urinary leakage and quality of life was analysed by ICIQ-SF. Statistical analysis was accomplished and the results rendered significant if p < 0.05. RESULTS: Mean follow up was 10 months (3 to 28). Mean age was 55 years (33 to 80), 70% were white and 30% African descendent, mean body mass index was 27 (21 to 38), average vaginal and abdominal deliveries were 2.8 and 0.5 respectively. A quarter had prior stress incontinence surgery. Patients with urethral hypermobility had higher objective success rates (98% versus 81.25%, p = 0.04). The subjective success rate was also greater in the hypermobility group (84% versus 62.5%), but statistical significance was not reached (p = 0.07). VLPP had no influence on either objective or subjective postoperative success rates (p = 0.17 and 0.34, respectively). In the subgroup analysis, those with low mobility and high VLPP had worse objective success rates in comparison to the group with hypermobility and low VLPP (p = 0.04) and also in relation to the remaining of the studied population. Other possible prognostic factors (previous surgery, mixed incontinence, gestational status) had no influence on success rates. CONCLUSIONS: High urethral mobility, regardless of the sphincteric status indicated by VLPP, is a favorable prognostic factor for tension-free transobturator tape procedure. No relationship was demonstrated between postoperative success rates and VLPP.

Statin Therapy Among Bariatric Patients: The Impact on Metabolic Outcomes and Diabetes Status.

INTRODUCTION: Statin therapy is associated with an increased risk of developing diabetes. Among bariatric patients, the influence of this therapy on various metabolic outcomes, such as diabetes status and its remission, is largely unknown. METHODS: This was a retrospective study of 1710 patients who underwent bariatric surgery at our hospital between January/2010 and June/2017. We compared patients with and without statin therapy at baseline, 12 and 24 months after surgery regarding statin use and its impact on several clinical and analytical parameters. Multiple linear regression was performed, adjusting differences for age, sex, surgery type, antidiabetic drugs at baseline, hypertension at baseline, LDL cholesterol ˃ 130 mg/dL, weight variation one year after surgery, and age of obesity onset. RESULTS: The overall prevalence of statin use was 20.2% before, 13.6% 12 months after surgery, and 15.0% 24 months after surgery. There was a larger reduction in fasting glucose and HbA1c at 12 and 24 months after surgery among statin-treated patients, with the opposite trend for weight reduction and BMI. Statin-treated patients with diabetes had lower diabetes remission rates (45.3 vs 68.5%) 12 months after surgery, with the highest reduction in HbA1c (1.3±1.3 vs -1.1±1.2%; p=0.042), fasting glucose (-40.8±48.8 vs -30.9±41.6 mg/dL; p=0.028), and insulin (-21.7±28.2 vs -13.4±14.2 mIU/L; p=0.039). The proportion of new-onset cases of diabetes was equal between statin-treated vs non-treated individuals at 12 months (1.9%) and 24 months (1.0%) after surgery. CONCLUSION: Bariatric surgery seems to lead to diabetes remission more frequently in patients not treated with statins. A larger reduction was observed in fasting glucose and HbA1c among statin-treated patients. Statin did not contribute to an increased proportion of new-onset diabetes after surgery.

Beta Cell Function as a Baseline Predictor of Weight Loss After Bariatric Surgery.

Background: Obesity is a multifactorial disease, which is strongly associated to other metabolic disorders. Bariatric surgery is the most effective treatment of morbid obesity. The role of beta cell function in weight loss after bariatric surgery is uncertain. Aim: To evaluate the association between beta cell function and percentage of total body weight loss (TBWL%) 1, 2, 3, and 4 years after bariatric surgery in patients with morbid obesity. Methods: Retrospective longitudinal study in patients with morbid obesity followed in our center between January 2010 and July 2018. Patients were excluded if they had diabetes at baseline or missing data on the needed parameters. We evaluated baseline Homeostatic Model Assessment of IR, Homeostatic Model Assessment of ß-cell function (HOMA-beta), Quantitative Insulin Sensitivity Check Index, and Matsuda and DeFronzo index, and TBWL% at years 1 to 4. Linear regression models were used to evaluate the association of indexes of insulin resistance with TBWL% (unadjusted and adjusted for age, sex, BMI, and type of surgery). Results: There were 1,561 patients included in this analysis. HOMA-beta was negatively associated with TBWL% at second, third, and fourth years post-surgery (ß = -1.04 [-1.82 to -0.26], p<0.01; ß = -1.16 [-2.13 to -0.19], p=0.02; ß = -1.29 [-2.64 to 0.06], p=0.061, respectively). This was not observed in the first year post-surgery nor for the other indexes. Glycemia at baseline was positively associated to EWL% at second and third years post-surgery. Conclusion: ß-cell function at baseline seems to be associated to long-term weight loss, explicitly after the first year post bariatric surgery. This might be a helpful predictor of weight loss in clinical practice.

Secondary Hyperparathyroidism Among Bariatric Patients: Unraveling the Prevalence of an Overlooked Foe.

INTRODUCTION: Bariatric surgery (BS) is the most effective therapeutic approach to obesity. It is associated with great gastrointestinal anatomic changes, predisposing the patients to altered nutrient absorption that impacts phosphocalcium metabolism. This study aimed to clarify the prevalence of secondary hyperparathyroidism (SHPT) and its predictors in patients submitted to BS. METHODS: Retrospective study of 1431 patients who underwent metabolic surgery between January 2010 and June 2017 and who were followed for at least 1 year. We compared the clinical and biochemical characteristics of patients with and without secondary hyperparathyroidism (considering SHPT a PTH ˃ 69 pg/mL). Two different analyses were performed: (1) paired analysis of participants before and 1 year after surgery (N = 441); (2) Cross sectional analysis of participants submitted to bariatric surgery before (N = 441), 1 year after (N = 1431) and 4 years after surgery (N = 333). Multiple logistic regression models were used to evaluate possible predictors of SHPT after BS. RESULTS: The overall prevalence of SHPT was 24.9% before surgery, 11.2% 1 year after surgery and 21.3% 4 years after surgery. Patients submitted to LAGB had the highest prevalence of SHPT 1 year after surgery (19.4%; vs RYGB, 12.8%, vs SG, 5.3%). Four years after surgery, RYGB had the highest prevalence of SHPT (27.0%), followed by LAGB (13.2%) and SG (6.9%). Higher body mass index and age, decreased levels of vitamin D and RYGB seem to be independent predictors of SHPT 1 year after surgery. The only independent predictor of SHPT 4 years after surgery was RYGB. CONCLUSION: The prevalence of SHPT is higher before and 4 years after BS than 1 year after surgery. This fact raises some questions about the efficacy of the implemented follow-up plans of vitamin D supplementation on the long term, mainly among patients submitted to RYGB.

The Impact of Vitamin D in Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study in Patients with Morbid Obesity.

PURPOSE: We aimed to evaluate the association between vitamin D status and hepatic function parameters and scores: Fatty Liver Index (FLI, predictor of hepatic steatosis) and BARD (BMI, AST/ALT ratio and DM, predictor of hepatic fibrosis) in patients with morbid obesity. PATIENTS AND METHODS: Cross-sectional study including patients with morbid obesity followed in our centre between January 2010 and July 2018. Patients with missing vitamin D levels or hepatic profile parameters were excluded. We divided the population according to two cut-offs of vitamin D levels (12ng/mL and 20ng/mL). RESULTS: The included population (n=1124) had an average age of 43.3±10.7 years and 84.3% were female. Seventy-point eight percent of the population had vitamin D levels lower than 20ng/mL and 34.8% lower than 12ng/dL. Patients with lower vitamin D levels (<12ng/mL) had higher BMI, hip and waist circumferences and higher prevalence of hypertension. Higher FLI scores [OR= 0.77 (0.07), p<0.01] and ALP levels [ß= -0.03 (-0.06, -0.01), p<0.01] associated to lower vitamin D levels. CONCLUSION: Vitamin D deficiency is associated with a higher risk of hepatic steatosis in individuals with morbid obesity. Correction of vitamin D deficiency may have a beneficial role in the management of NAFLD in patients with morbid obesity.

The Impact of Bariatric Surgery on Hepatic Function and Predictors of Liver Steatosis and Fibrosis.

PURPOSE: To evaluate the variation in parameters of hepatic function and in the scores Fatty Liver Index (FLI; predictor of hepatic steatosis) and BARD (BMI, AST/ALT ratio and DM, predictor of hepatic fibrosis), 1 year after bariatric surgery. MATERIAL AND METHODS: This is a observational retrospective cohort study in patients with morbid obesity that underwent bariatric surgery in our centre. We used two linear regression models: (1) unadjusted and (2) adjusted for surgery type, sex, age, body mass index, diabetes, and dyslipidaemia. RESULTS: The included population (n = 1955) had an average age of 43.1 ± 10 years and 85.8% were female. Diabetes was present in 32.4% of the patients, 45.1% had dyslipidaemia, and 62.2% had hypertension. Twelve percent were submitted to gastric band, 29.6% to sleeve gastrectomy, and 58.4% to gastric bypass. We observed a relevant decrease in transaminases and gamma-glutamyltransferase, and an increase in alkaline phosphatase and total bilirubin. Both FLI and BARD markedly decrease 1 year after surgery (p < 0.01). Comparing the surgical procedures, sleeve gastrectomy was associated with a greater reduction of hepatic enzymes and of both FLI and BARD compared with gastric band. Comparing with gastric bypass, sleeve was associated with a greater reduction of transaminases and alkaline phosphatase, but a smaller reduction of FLI and BARD. CONCLUSION: Bariatric surgery is associated with a reduction of the hepatic enzymes and an improvement of FLI and BARD. It may represent an effective therapeutic approach for NAFLD.

Antihypertensive potential of cis-[Ru(bpy)2(ImN)(NO)]3+, a ruthenium-based nitric oxide donor.

The aim of this study was to investigate the antihypertensive properties of cis-[Ru(bpy)2ImN(NO)]3+ (FOR0811) in normotensive and in Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Vasorelaxant effects were analyzed by performing concentration response curve to FOR0811 in rat aortic rings in the absence or presence of 1H-[1,2,4]-oxadiazolo-[4,3,-a]quinoxalin-1-one (ODQ), L-cysteine or hydroxocobalamin. Normotensive and L-NAME-hypertensive rats were treated with FOR0811 and the effects in blood pressure and heart rate variability in the frequency domain (HRV) were followed. FOR0811 induced relaxation in rat aortic rings. Neither endothelium removal nor L-cysteine altered the FOR0811 effects. However, the incubation with ODQ and hydroxocobalamin completely blunted FOR0811 effects. FOR0811 administered intravenously by bolus infusion (0.01-1 mg/bolus) or chronically by using subcutaneous implanted osmotic pumps significantly reduced the mean arterial blood pressure. The effect was long lasting and did not induce reflex tachycardia. FOR0811 prevented both LF and VLF increases in L-NAME hypertensive rats and has antihypertensive properties. This new ruthenium complex compound might be a promising nitric oxide donor to treat cardiovascular diseases.

Thyroid Function and the Risk of Non-Alcoholic Fatty Liver Disease in Morbid Obesity.

Background: An association between hypothyroidism and the risk of Non-alcoholic Fatty Liver Disease (NAFLD) has been suggested. This association remains to be elucidated in patients with morbid obesity. Aim: To evaluate the association between thyroid function and parameters of liver function and hepatic scores in patients with morbid obesity. Methods: Patients with morbid obesity followed in our center between January 2010 and July 2018 were included. The ones without evaluation of liver and thyroid functions were excluded. Fatty Liver Index (FLI) and BARD scores were used as predictors of hepatic steatosis and fibrosis, respectively. Results: We observed a positive association between TSH and both BARD (OR 1.14; p = 0.035) and FLI (OR 1.19; p = 0.010) in the unadjusted analysis. We found a negative association between free triiodothyronine levels and BARD (OR 0.70; p<0.01) and a positive association between free triiodothyronine levels and FLI (OR 1.48; p = 0.022). Concerning liver function, we found a positive association between total bilirubin and free thyroxine levels (ß = 0.18 [0.02 to 0.35]; p = 0.033) and a negative association between total bilirubin and free triiodothyronine levels (ß = -0.07 [-0.14 to -0.002]; p = 0.042). Conclusion: Higher levels of TSH and free triiodothyronine may be associated with a higher risk of NAFLD, particularly steatosis, in patients with morbid obesity.

A divergent mode of activation of a nitrosyl iron complex with unusual antiangiogenic activity.

Nitric oxide (NO) and nitroxyl (HNO) have gained broad attention due to their roles in several physiological and pathophysiological processes. Remarkably, these sibling species can exhibit opposing effects including the promotion of angiogenic activity by NO compared to HNO, which blocks neovascularization. While many NO donors have been developed over the years, interest in HNO has led to the recent emergence of new donors. However, in both cases there is an expressive lack of iron-based compounds. Herein, we explored the novel chemical reactivity and stability of the trans-[Fe(cyclam)(NO)Cl]Cl2 (cyclam = 1,4,8,11-tetraazacyclotetradecane) complex. Interestingly, the half-life (t1/2) for NO release was 1.8 min upon light irradiation, vs 5.4 h upon thermal activation at 37 °C. Importantly, spectroscopic evidence supported the generation of HNO rather than NO induced by glutathione. Moreover, we observed significant inhibition of NO donor- or hypoxia-induced HIF-1α (hypoxia-inducible factor 1α) accumulation in breast cancer cells, as well as reduced vascular tube formation by endothelial cells pretreated with the trans-[Fe(cyclam)(NO)Cl]Cl2 complex. Together, these studies provide the first example of an iron-nitrosyl complex with anti-angiogenic activity as well as the potential dual activity of this compound as a NO/HNO releasing agent, which warrants further pharmacological investigation.

Modelling youth pregnancy in continental Portugal through geographically weighted regression.

Youth pregnancy, a global public health problem with important social, educational and economic impact, has mostly been studied in the least developed countries. However, this condition also affects the industrialized countries. This article presents a youth pregnancy study at the municipality level in continental Portugal based on geographically weighted regression. The results indicate that youth pregnancy rates can be explained by several variables: i) proportion (%) of social security beneficiaries; ii) number of households without amenities; iii) the rate of those prematurely leaving school; iv) the unemployment rates of youths and females, ceteris paribus. In addition, it was found that the beneficiaries of social security had a higher impact on youth pregnancy in the southern part of the country, and in the Centre too; that households without amenities had a higher impact along the central coast and in the South; that rates of those leaving school prematurely had a higher influence in the North and the Interior than in the rest of the country; and that youth and female unemployment rates were more widespread in the Centre, particularly along the coast. Overall, the model identified a strong association of explanatory variables with youth pregnancy rates in the country as a whole, except in the Porto metropolitan area. These findings may help health planners to define policies to mitigate this important social problem.