Association between heavy alcohol consumption and cryptogenic ischaemic stroke in young adults: a case-control study.

BACKGROUND: The underlying risk factors for young-onset cryptogenic ischaemic stroke (CIS) remain unclear. This multicentre study aimed to explore the association between heavy alcohol consumption and CIS with subgroup analyses stratified by sex and age. METHODS: Altogether, 540 patients aged 18-49 years (median age 41; 47.2% women) with a recent CIS and 540 sex-matched and age-matched stroke-free controls were included. Heavy alcohol consumption was defined as >7 (women) and >14 (men) units per week or at least an average of two times per month ≥5 (women) and ≥7 (men) units per instance (binge drinking). A conditional logistic regression adjusting for age, sex, education, hypertension, cardiovascular diseases, diabetes, hypercholesterolaemia, current smoking, obesity, diet and physical inactivity was used to assess the independent association between alcohol consumption and CIS. RESULTS: Patients were twice as more often heavy alcohol users compared with controls (13.7% vs 6.7%, p<0.001), were more likely to have hypertension and they were more often current smokers, overweight and physically inactive. In the entire study population, heavy alcohol consumption was independently associated with CIS (adjusted OR 2.11; 95% CI 1.22 to 3.63). In sex-specific analysis, heavy alcohol consumption was associated with CIS in men (2.72; 95% CI 1.25 to 5.92), but not in women (1.56; 95% CI 0.71 to 3.41). When exploring the association with binge drinking alone, a significant association was shown in the entire cohort (2.43; 95% CI 1.31 to 4.53) and in men (3.36; 95% CI 1.44 to 7.84), but not in women. CONCLUSIONS: Heavy alcohol consumption, particularly binge drinking, appears to be an independent risk factor in young men with CIS.

Standard Doses of Cholecalciferol Reduce Glucose and Increase Glutamine in Obesity-Related Hypertension: Results of a Randomized Trial.

In arterial hypertension, the dysregulation of several metabolic pathways is closely associated with chronic immune imbalance and inflammation progression. With time, these disturbances lead to the development of progressive disease and end-organ involvement. However, the influence of cholecalciferol on metabolic pathways as a possible mechanism of its immunomodulatory activity in obesity-related hypertension is not known. In a phase 2, randomized, single-center, 24-week trial, we evaluated, as a secondary outcome, the serum metabolome of 36 age- and gender-matched adults with obesity-related hypertension and vitamin D deficiency, before and after supplementation with cholecalciferol therapy along with routine medication. The defined endpoint was the assessment of circulating metabolites using a nuclear magnetic resonance-based metabolomics approach. Univariate and multivariate analyses were used to evaluate the systemic metabolic alterations caused by cholecalciferol. In comparison with normotensive controls, hypertensive patients presented overall decreased expression of several amino acids (p < 0.05), including amino acids with ketogenic and glucogenic properties as well as aromatic amino acids. Following cholecalciferol supplementation, increases were observed in glutamine (p < 0.001) and histidine levels (p < 0.05), with several other amino acids remaining unaffected. Glucose (p < 0.05) and acetate (p < 0.05) decreased after 24 weeks in the group taking the supplement, and changes in the saturation of fatty acids (p < 0.05) were also observed, suggesting a role of liposoluble vitamin D in lipid metabolism. Long-term cholecalciferol supplementation in chronically obese and overweight hypertensives induced changes in the blood serum metabolome, which reflected systemic metabolism and may have fostered a new microenvironment for cell proliferation and biology. Of note, the increased availability of glutamine may be relevant for the proliferation of different T-cell subsets.

Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A-Rearranged Acute Lymphoblastic and Myeloid Leukemia.

Pediatric acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) exhibit favorable survival rates. However, for AML and ALL patients carrying KMT2A gene translocations clinical outcome remains unsatisfactory. Key players in KMT2A-fusion-driven leukemogenesis include menin and DOT1L. Recently, menin inhibitors like revumenib have garnered attention for their potential therapeutic efficacy in treating KMT2A-rearranged acute leukemias. However, resistance to menin inhibition poses challenges, and identifying which patients would benefit from revumenib treatment is crucial. Here, we investigated the in vitro response to revumenib in KMT2A-rearranged ALL and AML. While ALL samples show rapid, dose-dependent induction of leukemic cell death, AML responses are much slower and promote myeloid differentiation. Furthermore, we reveal that acquired resistance to revumenib in KMT2A-rearranged ALL cells can occur either through the acquisition of MEN1 mutations or independently of mutations in MEN1. Finally, we demonstrate significant synergy between revumenib and the DOT1L inhibitor pinometostat in KMT2A-rearranged ALL, suggesting that such drug combinations represent a potent therapeutic strategy for these patients. Collectively, our findings underscore the complexity of resistance mechanisms and advocate for precise patient stratification to optimize the use of menin inhibitors in KMT2A-rearranged acute leukemia.

Factors Associated with Prospective Acceptability and Preferences for Unified Transdiagnostic Cognitive-Behavioral Treatments and Group Therapy in the Portuguese General Population.

Group transdiagnostic cognitive-behavioral therapy (CBT) offers a promising solution for limited mental health access in Portugal. Understanding barriers to patient adherence is crucial for successful implementation. This study aimed to characterize the prospective acceptability and preferences for unified transdiagnostic CBT and group therapy in the Portuguese general population and explore their correlates. A sample of 243 participants (18-88 years old), recruited online, completed an online survey collecting information on sociodemographic and clinical characteristics, acceptability of transdiagnostic CBT treatments, specifically of Unified Protocol (UP), acceptability of group therapy, therapeutic format preferences, beliefs about group therapy and help-seeking attitudes. Most participants were receptive to and perceived as useful both unified transdiagnostic CBT and group therapy. Overall, participants presented significantly more favorable attitudes than unfavorable attitudes toward unified transdiagnostic CBT and group therapy (p < .001). Multivariate analyses revealed that (1) favorable attitudes toward transdiagnostic treatments were negatively associated with being employed and positively associated with living in an urban area, and higher efficacy scores; (2) unfavorable attitudes toward transdiagnostic treatments were positively associated with being married/cohabitating and negatively associated with vulnerability scores; (3) being female, living in an urban area, and higher efficacy and myth scores emerged as positive predictors of favorable attitudes toward group therapy; and (4) efficacy and vulnerability scores and help-seeking propensity emerged as negative predictors of unfavorable attitudes toward group therapy. These findings highlight the importance of delineating strategies to increase knowledge and acceptance of unified transdiagnostic CBT and group therapy in the Portuguese population, addressing specific individual characteristics.

SchoolAIR: A Citizen Science IoT Framework Using Low-Cost Sensing for Indoor Air Quality Management.

Indoor air quality (IAQ) problems in school environments are very common and have significant impacts on students' performance, development and health. Indoor air conditions depend on the adopted ventilation practices, which in Mediterranean countries are essentially based on natural ventilation controlled through manual window opening. Citizen science projects directed to school communities are effective strategies to promote awareness and knowledge acquirement on IAQ and adequate ventilation management. Our multidisciplinary research team has developed a framework-SchoolAIR-based on low-cost sensors and a scalable IoT system architecture to support the improvement of IAQ in schools. The SchoolAIR framework is based on do-it-yourself sensors that continuously monitor air temperature, relative humidity, concentrations of carbon dioxide and particulate matter in school environments. The framework was tested in the classrooms of University Fernando Pessoa, and its deployment and proof of concept took place in a high school in the north of Portugal. The results obtained reveal that CO2 concentrations frequently exceed reference values during classes, and that higher concentrations of particulate matter in the outdoor air affect IAQ. These results highlight the importance of real-time monitoring of IAQ and outdoor air pollution levels to support decision-making in ventilation management and assure adequate IAQ. The proposed approach encourages the transfer of scientific knowledge from universities to society in a dynamic and active process of social responsibility based on a citizen science approach, promoting scientific literacy of the younger generation and enhancing healthier, resilient and sustainable indoor environments.

HIV infection among children in Malanje province, Angola: a twelve-year follow-up study.

INTRODUCTION: Human immunodeficiency virus (HIV) / acquired immunodeficiency syndrome (AIDS) infection has been a serious health problem in pediatric age groups globally, and especially in African countries such as Angola. Our aim was to determine the prevalence rate, accumulate incidence rate, and mortality rate of HIV/AIDS infection in children under 14 years of age residing in four municipalities of Malanje (Malanje, Cacuso, Calandula, and Caculama), from 2010 to 2021. METHODOLOGY: This was a documentary research study, with data from 2010 to 2021, developed from a sample size of 10,984 children. RESULTS: The prevalence rate data showed a certain level of dispersion, and no relationship was identified in its behavior over the years (R2 = 0.0036). On the other hand, the accumulate incidence rate presented a tendency to decrease, indicating a moderate level of correlation in its behavior over the years (R2 = 0.4278). Finally, the mortality rate has been decreasing and presented a high correlation in its association with the years under analysis (R2 = 0.8142). Primary schooling and low purchasing power were frequent (60% and 82%, respectively) among the families of HIV-infected children under study. CONCLUSIONS: Despite the temporal variation of HIV in children under 14 years of age living in the different municipalities, there was a tendency of its diminishing in the later part of the period, from 2010 to 2021. Nevertheless, the key players should focus on strengthening community strategies for prevention, investigation, and diagnosis of HIV infections in this population.

The relationship between healthcare satisfaction after miscarriage and perinatal grief symptoms: A cross-sectional study on Portugal residents.

OBJECTIVE: 15-20% of identified pregnancies result in miscarriage, which may lead to persistent symptoms of psychological morbidities in some women. Healthcare satisfaction is among the factors believed to influence such negative psychological responses. Here, we present the results of a study conducted in Portugal that analyzes the relationship between healthcare satisfaction, information and support provision and perinatal grief symptoms. METHODS: In a cross-sectional study, symptoms of perinatal grief, degree of satisfaction with healthcare received, and information and support provision data were collected through an online survey aimed at women in Portugal who suffered a miscarriage. 873 were considered eligible. Correlations were performed between perinatal grief scores and healthcare satisfaction rates. Finally, the proportions of information and support received were compared after distributing the sample in groups according to their perinatal grief levels. RESULTS: Healthcare satisfaction correlated significantly with perinatal grief scores, the latter increasing as satisfaction levels decreased. 61.1% of our sample received information about the physical consequences of miscarriage and showed a significantly lower rate of above-threshold perinatal grief symptoms in this group. 18.2% received information about its mental health consequences, with no significant differences in above-threshold symptom rates. 11.7% were offered or recommended mental health support, but no significant differences in above-threshold symptom rates were found. CONCLUSION: Healthcare satisfaction and information on after-miscarriage physical changes correlated significantly with reduced perinatal grief rates after miscarriage. However, any effects of mental health information and psychological support provision need further studies. Training for healthcare providers dealing with pregnancy loss, implementing national guidelines that include follow-up on the parents' physical and psychological health, and including a specialized area in medical structures are advised.

Relapsing-remitting multiple sclerosis patients exhibit differential natural killer functional subpopulations.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) and has been known as T-cell mediated. However, the contribution of multiple cell types, notably natural killer (NK) cells, has also been reported. AIM: To quantify circulating total NK cells and its subpopulations, CD56 dim and bright, and to characterize the functional phenotype and IFN-γ and TNF-α production in relapsing-remitting patients treated with IFN-ß and in apparently healthy controls. RESULTS: CD56bright NK cells were found to be the least represented subpopulation. In relapse patients, the frequencies of IFN-γ-producing NK cells and their subpopulations were significantly decreased. In remission patients, CD56dim NK cells expressed high levels of HLA-DR and CD54. CONCLUSION: These results suggest that remission RRMS patients, although in an inactive stage of MS, present circulating NK cells with an activation phenotype, supporting the idea that NK cells may be relevant mediators in the MS pathophysiology.

Characteristics and patient-reported outcomes of long-term lung cancer survivors.

Background: Due to advances in screening and treatment of lung cancer, there has been increased interest in long-term lung cancer survivors (LTLCS). The aim of this study was to evaluate the prevalence of LTLCS, their characteristics and patient-reported outcomes (PROs) of LTLCS. Methods: Cross-sectional study that included patients diagnosed with primary lung cancer between Jan 2012 and Dec 2016 whose overall survival (OS) was greater than 5 years. A self-administered questionnaire was applied, including European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30), Patient Health Questionnaire-4 (PHQ-4) and two open questions regarding quality of life (QoL) and suggestions for improvements. Factors potentially related to QoL were analysed. Results: Of 767 lung cancer patients, 158 (20.6%) were LTLCS and LTLCS' proportion increased yearly. Most patients were male (70.9%) with median age of 65 [interquartile range (IQR), 56-71] years. Fifty-seven percent had adenocarcinoma, 66.2% were diagnosed at early stages but 8.9% were at stage IV. During follow-up, 77.1% quitted smoking, 31.8% had disease progression/relapse and 15.2% developed other tumours. Of all living LTLCS, 100 (85%) patients answered the PROs questionnaire. The median Global Health score was 66.67 (IQR, 50-83), social functioning had the best score and emotional functioning the worst. Pain and fatigue were the symptoms with the worst impact on QoL. PHQ-4 identified mental distress in 36% and patients with a lower QoL were more likely to present anxiety (35.3% vs. 9.4%, P=0.007) or depression (27.9% vs. 3%, P=0.006). In the open questions, patients reported pain (17%), lack of familiar/financial support (16%), dyspnoea (14%), depression (8%), concern for the future (8%) and limitations performing daily activities (8%) as the aspects with most impact in QoL. The most suggested measures were improvement of care provided by health institutions (25%) and better social support (16%). Conclusions: Prevalence of LTLCS is increasing and survivors may experience a high prevalence of anxiety and depression as well as a high disease burden affecting QoL. Therefore, it's important to provide multidisciplinary continuous patient-centred care and a careful follow-up for all lung cancer patients, including LTLCS.

Development of handling energy factors for use of dustiness data in exposure assessment modelling.

Several exposure assessment models use dustiness as an input parameter for scaling or estimating exposure during powder handling. Use of different dustiness methods will result in considerable differences in the dustiness values as they are based on different emission generation principles. EN17199:2019 offers 4 different dustiness test methods considering different dust release scenarios (e.g. powder pouring, mixing and gentle agitation, and vibration). Conceptually, the dustiness value by a given method can be multiplied with a scenario-specific modifier, called a handling energy factor (Hi), that allows conversion of a dustiness value to a release constant. Therefore, a Hi, scaling the effective mechanical energy in the process to the energy supplied in the specific dustiness test, needs to be applied. To improve the accuracy in predictive exposure modelling, we derived experimental Hi to be used in exposure algorithms considering both the mass- and number-based dust release fraction determined by the EN17199-3 continuous drop (CD) and the EN17199-4 small rotating drum (SRD) test methods. Three materials were used to evaluate the relationship between dustiness and dust levels during pouring powder from different heights in a controlled environment. The results showed increasing scatter and difference between the Hi derived for the 2 test methods with increasing pouring height. Nearly all the Hi values obtained for both SRD and CD were <1 indicating that the dustiness tests involved more energy input than the simulated pouring activity and consequently de-agglomeration and dust generation were higher. This effect was most pronounced in CD method showing that SRD mechanistically resembles more closely the powder pouring.

Economic evaluation of Be a Mom, a web-based intervention to prevent postpartum depression in high-risk women alongside a randomized controlled trial.

BACKGROUND: Postpartum depression (PPD) poses significant challenges, affecting both mothers and children, with substantial societal and economic implications. Internet-based cognitive behavioral therapy interventions (iCBT) offer promise in addressing PPD, but their economic impact remains unexplored. This study aimed to evaluate the cost-utility of Be a Mom, a self-guided iCBT intervention, compared with a waiting-list control among postpartum women at high risk of PPD. METHODS: This economic evaluation was conducted alongside a 14-month randomized controlled trial adopting a societal perspective. Participants were randomized to Be a Mom (n = 542) or a waitlisted control group (n = 511). Self-report data on healthcare utilization, productivity losses, and quality-adjusted life years (QALYs) were collected at baseline, post-intervention, and 4 and 12 months post-intervention. Incremental cost-effectiveness ratios (ICERs) were calculated, and cost-effectiveness acceptability curves were generated using nonparametric bootstrapping. Sensitivity analyses were conducted to assess result robustness. RESULTS: Over 14 months, Be a Mom generated a QALY gain of 0.0184 (0.0022, 0.0346), and cost savings of EUR 34.06 (-176.16, 108.04) compared to the control group. At a willingness to pay of EUR 20,000, Be a Mom had a 97.6 % probability of cost-effectiveness. LIMITATIONS: Results have limitations due to self-selected sample, potential recall bias in self-reporting, missing data, limited follow-up, and the use of a waiting-list control group. CONCLUSIONS: This study addresses a critical gap by providing evidence on the cost-utility of an iCBT intervention tailored for PPD prevention. Further research is essential to identify scalable and cost-effective interventions for reducing the burden of PPD.

Use of the dustiness index in combination with the handling energy factor for exposure modelling of nanomaterials.

The use of modelling tools in the occupational hygiene community has increased in the last years to comply with the different existing regulations. However, limitations still exist mainly due to the difficulty to obtain certain key parameters such as the emission rate, which in the case of powder handling can be estimated using the dustiness index (DI). The goal of this work is to explore the applicability and usability of the DI for emission source characterization and occupational exposure prediction to particles during nanomaterial powder handling. Modelling of occupational exposure concentrations of 13 case scenarios was performed using a two-box model as well as three nano-specific tools (Stoffenmanager nano, NanoSafer and GUIDEnano). The improvement of modelling performance by using a derived handling energy factor (H) was explored. Results show the usability of the DI for emission source characterization and respirable mass exposure modelling of powder handling scenarios of nanomaterials. A clear improvement in modelling outcome was obtained when using derived quartile-3 H factors with, 1) Pearson correlations of 0.88 vs. 0.52 (not using H), and 2) ratio of modelled/measured concentrations ranging from 0.9 to 10 in 75% cases vs. 16.7% of the cases when not using H. Particle number concentrations were generally underpredicted. Using the most conservative H values, predictions with ratios modelled/measured concentrations of 0.4-3.6 were obtained.

For Whom and for How Long Does the "Be a Mom" Intervention Work? A Secondary Analysis of Data From a Randomized Controlled Trial Exploring the Mid-Term Efficacy and Moderators of Treatment Response.

This study explored clinical and sociodemographic moderators of treatment response to "Be a Mom", an internet-based cognitive behavioral therapy (iCBT) intervention, from baseline to postintervention, in women at high risk for postpartum depression (PPD). The study also assessed the stability of women's treatment gains from baseline to 4-months postintervention (follow-up). This open-label randomized controlled trial (RCT) involved a sample of 1,053 postpartum Portuguese women identified as being at high risk for PPD (i.e., having a score of 5.5 or higher on the Postpartum Depression Predictors Inventory-Revised); participants were allocated to "Be a Mom" intervention group or a waiting-list control group, and completed self-report measures at baseline, postintervention, and a 4-month follow-up (554 women completed follow-up assessments). Depressive and anxiety symptoms were measured using the Edinburgh Postnatal Depression Scale and the anxiety subscale of the Hospital Anxiety and Depression Scale, and flourishing/positive mental health was assessed with the Mental Health Continuum. Regression models and linear mixed models were used to examine moderators of treatment and the mid-term efficacy of the "Be a Mom" intervention, respectively. The results revealed that treatment completion, higher depression scores at baseline, and higher income levels were linked to greater symptom reduction and positive mental health enhancement. Moreover, the efficacy of the "Be a Mom" intervention was supported at the 4-month follow-up. The "Be a Mom" intervention appears to be an effective iCBT tool for reducing psychological distress and enhancing positive mental health in women at risk for PPD, with therapeutic improvements maintained over a 4-month period.

Silica-Poly(Vinyl Alcohol) Composite Aerogel: A Promising Electrolyte for Solid-State Sodium Batteries.

The transition from fossil fuels is in part limited by our inability to store energy at different scales. Batteries are therefore in high demand, and we need them to store more energy, be more reliable, durable and have less social and environmental impact. Silica-poly(vinyl alcohol) (PVA) composite aerogels doped with sodium perchlorate were synthesized as novel electrolytes for potential application in solid-state sodium batteries. The aerogels, synthesized by one-pot synthesis, are light (up to 214 kg m-3), porous (~85%), exhibit reduced shrinkage on drying (up to 12%) and a typical silica aerogel microstructure. The formation of a silica network and the presence of PVA and sodium perchlorate in the composite were confirmed by FTIR and TGA. The XRD analysis also shows that a predominantly amorphous structure is obtained, as crystalline phases of polymer and salt are present in a very reduced amount. The effects of increasing polymer and sodium salt concentrations on the ionic conductivity, assessed via electrochemical impedance spectroscopy, were studied. At a PVA concentration of 15% (w/w silica precursors), the sodium conduction improved significantly up to (1.1 ± 0.3) × 10-5 S cm-1. Thus, this novel material has promising properties for the envisaged application.

Psychometric properties of the Decisional Conflict Scale in a sample of perinatal women with depressive symptoms: A study in Portugal and Norway.

OBJECTIVE: To assess the psychometric properties, i.e., reliability and construct validity of the 16-item Decisional Conflict Scale (DCS) and sub-scales in women with perinatal depressive symptoms in Norway and Portugal. METHODS: We included 415 women in Portugal and 163 in Norway (≥18 years) who were pregnant or had given birth in the last 12 months and presenting with active depressive symptoms. Women replied to the original DCS items. We conducted confirmatory factor analysis, estimated internal consistency reliability, and examined factorial invariance across country, perinatal status, and treatment uptake. RESULTS: The DCS factor model had good fit to the data, with all items loading significantly on their respective factor (.585 to .958). There was configural invariance of the DCS across countries, treatment, and perinatal status. The internal consistency of the total DCS (Cronbach's alpha) was .958, and for the subscales it ranged from .798 to .947. CONCLUSIONS: The DCS is a valid and reliable measure of the decisional conflict in women with perinatal depressive symptoms in Portugal and Norway. PRACTICE IMPLICATIONS: Measuring the extent of decisional conflict regarding treatment and the effect of multiple interventions towards its reduction, is critical to facilitate the decision-making process of women with perinatal mental illness.

Association of Meal Timing with Sleep Quality and Anxiety According to Chronotype: A Study of University Students.

There are several determinants of mental health symptoms, ranging from individual characteristics to social factors. Consistent with patterns in the general population, students with evening characteristics tend to exhibit more anxiety symptoms and poorer sleep quality compared to morning students. Meal timing also appears to affect sleep and may be associated with mental health symptoms. In this context, the aim of the present study was to investigate the association of the timing of the main and last meals of the day with sleep quality and anxiety levels, according to the chronotype of university students. This study was conducted in colleges in São Paulo, Brazil, and involved application of a questionnaire to 162 university students. The questionnaire collected sociodemographic information meal and study times, and included scales assessing eveningness and morningness, sleep quality, and anxiety. Students demonstrating a phase delay in both chronotype and dinner timing exhibited higher levels of anxiety compared to morning-type students. Although no associations were observed between meal timing and sleep quality, sleeping later was associated with poorer sleep quality. The study suggests that evening students and those who eat late at night are more prone to presenting mental health symptoms. More studies are needed to further investigate this association.

Extensively drug-resistant Pseudomonas aeruginosa: clinical features and treatment with ceftazidime/avibactam and ceftolozane/tazobactam in a tertiary care university hospital center in Portugal - A cross-sectional and retrospective observational study.

Introduction: Extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) is a growing concern due to its increasing incidence, limited therapeutic options, limited data on the optimal treatment, and high mortality rates. The study aimed to characterize the population, the outcome and the microbiological characteristics of XDR-PA identified in a Portuguese university hospital center. Methods: All XDR-PA isolates between January 2019 and December 2021 were identified. XDR-PA was defined as resistance to piperacillin-tazobactam, third and fourth generation cephalosporins, carbapenems, aminoglycosides and fluoroquinolones. A retrospective analysis of the medical records was performed. Results: One hundred seventy-eight individual episodes among 130 patients with XDR-PA detection were identified. The most common sources of infection were respiratory (32%) and urinary tracts (30%), although skin and soft tissue infections (18%) and primary bacteremia (14%) were also prevalent. Colonization was admitted in 64 cases. Several patients had risk factors for complicated infections, most notably immunosuppression, structural lung abnormalities, major surgery, hemodialysis or foreign intravascular or urinary devices. XDR-PA identification was more frequent in male patients with an average age of 64.3 ± 17.5 years. One non-susceptibility to colistin was reported. Only 12.4% were susceptible to aztreonam. Ceftazidime-avibactam (CZA) was susceptible in 71.5% of the tested isolates. Ceftolozane-tazobactam (C/T) was susceptible in 77.5% of the tested isolates. Antibiotic regimens with XDR-PA coverage were reserved for patients with declared infection, except to cystic fibrosis. The most frequently administered antibiotics were colistin (41 cases), CZA (39 cases), and C/T (16 cases). When combination therapy was used, CZA plus colistin was preferred. The global mortality rate among infected patients was 35.1%, significantly higher in those with hematologic malignancy (50.0%, p < 0.05), followed by the ones with bacteremia (44.4%, p < 0.05) and those medicated with colistin (39.0%, p < 0.05), especially the ones with respiratory infections (60.0%). Among patients treated with CZA or C/T, the mortality rate seemed to be lower. Discussion: XDR-PA infections can be severe and difficult to treat, with a high mortality rate. Even though colistin seems to be a viable option, it is likely less safe and efficient than CZA and C/T. To the best of the authors' knowledge, this is the first description of the clinical infection characteristics and treatment of XDR-PA in Portugal.

Impact of elevated lipoprotein(a) on coronary artery disease phenotype and severity.

AIMS: A thorough characterization of the relationship between elevated lipoprotein(a) [Lp(a)] and coronary artery disease (CAD) is lacking. This study aimed to quantitatively assess the association of increasing Lp(a) levels and CAD severity in a real-world population. METHODS AND RESULTS: This non-interventional, cross-sectional, LipidCardio study included patients aged ≥21 years undergoing angiography (October 2016-March 2018) at a tertiary cardiology centre, who have at least one Lp(a) measurement. The association between Lp(a) and CAD severity was determined by synergy between PCI with taxus and cardiac surgery (SYNTAX)-I and Gensini scores and angiographic characteristics. Overall, 975 patients (mean age: 69.5 years) were included; 70.1% were male, 97.5% had Caucasian ancestry, and 33.2% had a family history of premature atherosclerotic cardiovascular disease. Median baseline Lp(a) level was 19.3 nmol/L. Patients were stratified by baseline Lp(a): 72.9% had < 65 nmol/L, 21.0% had ≥100 nmol/L, 17.2% had ≥125 nmol/L, and 12.9% had ≥150 nmol/L. Compared with the normal (Lp(a) < 65 nmol/L) group, elevated Lp(a) groups (e.g. ≥ 150 nmol/L) had a higher proportion of patients with prior CAD (48.4% vs. 62.7%; P < 0.01), prior coronary revascularization (39.1% vs. 51.6%; P = 0.01), prior coronary artery bypass graft (6.0% vs. 15.1%; P < 0.01), vessel(s) with lesions (68.5% vs. 81.3%; P = 0.03), diffusely narrowed vessels (10.9% vs. 16.5%; P = 0.01) or chronic total occlusion lesions (14.3% vs. 25.2%; P < 0.01), and higher median SYNTAX-I (3.0 vs. 5.5; P = 0.01) and Gensini (10.0 vs. 16.0; P < 0.01) scores. CONCLUSION: Elevated Lp(a) was associated with a more severe presentation of CAD. Awareness of Lp(a) levels in patients with CAD may have implications in their clinical management.

Patients with coronary artery disease (CAD) suffer with progressive plaque buildup in the walls of coronary blood vessels, which restricts blood flow and may result in serious cardiovascular outcomes such as chest pain (angina) and heart attacks (myocardial infarction). In this study, we assessed whether elevated levels of lipoprotein(a) [Lp(a)­a lipoprotein found in blood] are associated with more severe illness. We observed that elevated Lp(a) was associated with a higher proportion of patients with prior CAD, prior interventions on coronary blood vessels, and more diseased blood vessels. These collectively form what is considered a 'severe' clinical presentation of CAD, meaning a greater likelihood of adverse clinical outcomes.

Indoor paint life cycle particle release: Safer-by-design products and the importance of choosing the right formula.

In 2020, the European Commission published a regulation that states all producers of white paints containing titanium dioxide (TiO2) must provide a warning label on their products. Exposure during the production and application of products containing TiO2 can be harmful, and therefore these products must be labeled as "may cause cancer." The paint industry is a major user of TiO2 pigment. This study focuses on pigment release from three TiO2-based paints and discusses the effect of paint formulation, more precisely the Pigment Volume Concentration (PVC), to predict TiO2 pigment release from the paints during a simulated use phase and at the end of life (EoL). The use phase considered mild abrasion of painted panels that simulated cleaning or touching. The EoL phase was studied using leaching tests simulating landfill disposal. TiO2 release during both activities was evident with a high discrepancy between the three paints. While dry rubbing was similar for all paints, activities involving water present a high release link to paint matrix degradation. The paint pigment volume concentration and the paint permeability determines the TiO2 release during wet rubbing and leaching. This work represents an attempt to identify the paint permeability as a matrix-related parameter to predict TiO2 release and a way to use of this parameter to develop safer products.

Investigating antibiotic free feed additives for growth promotion in poultry: effects on performance and microbiota.

The poultry industry is evolving towards antibiotic-free production to meet market demands and decelerate the increasing spread of the antimicrobial resistance. The growing need for antibiotic free products has challenged producers to decrease or completely stop using antimicrobials as feed supplements in broiler diet to improve feed efficiency, growth rate, and intestinal health. Natural feed additives (e.g., probiotics and phytobiotics) are promising alternatives to substitute antimicrobial growth promoters. The goal of our study was to characterize the effects of a Probiotic and an Essential Oils blend on broilers' performance and perform a time-series analysis to describe their excreta microbiome. A total of 320 Cobb 500 (1-day-old) chicks were raised for 21 d in 32 randomly allocated cages. Treatments consisted of 4 experimental diets: a basal diet, and a basal diet mixed with an Antibiotic (bacitracin methylene disalicylate), an essential oils blend (oregano oil, rosemary, and red pepper), or a Probiotic (Bacillus subtilis). Body weight (on 1, 10, and 21d), and feed intake (10d and 21d) were recorded and feed conversion ratio was calculated. Droppings were collected daily (1-21d) to characterize broilers' excreta microbiota by targeted sequencing of the bacterial 16S rRNA gene. The Probiotic significantly improved feed conversion ratio for starter phase 1 to 10d (P = 0.03), grower phase 10 to 21d (P = 0.05), and total period 1 to 21d (P = 0.01) compared to the Antibiotic. Feed supplements did not affect alpha diversity but did impact microbial beta diversity (P < 0.01). Age also impacted microbiome turnover as differences in alpha and beta diversity were detected. Furthermore, when compared to the basal diet, the probiotic and antibiotic significantly impacted relative abundance of Bifidobacterium (log2 fold change -1.44, P = 0.03), Intestinimonas (log2 fold change 0.560, P < 0.01) and Ligilactobacillus (log2 fold change -1.600, P < 0.01). Overall, Probiotic supplementation but not essential oils supplementation positively impacted broilers' growth performance by directly causing directional shifts in broilers' excreta microbiota structure.