A novel combinatory treatment against a CDDP-resistant non-small cell lung cancer based on a Ruthenium(II)-cyclopentadienyl compound.

The therapeutic approach to many solid tumors, including non-small cell lung cancer (NSCLC), is mainly based on the use of platinum-containing anticancer agents and is often characterized by acquired or intrinsic resistance to the drug. Therefore, the search for safer and more effective drugs is still an open challenge. Two organometallic ruthenium(II)-cyclopentadienyl compounds [Ru(η5-C5H4CHO)(Me2bipy)(PPh3)]+ (RT150) and [Ru(η5-C5H4CH2OH)(Me2bipy)(PPh3)][CF3SO3] (RT151) were tested against a panel of cisplatin-resistant NSCLC cell lines and xenografts. They were more effective than cisplatin in inducing oxidative stress and DNA damage, affecting the cell cycle and causing apoptosis. Importantly, they were found to be inhibitors of drug efflux transporters. Due to this property, the compounds significantly increased the retention and cytotoxicity of cisplatin within NSCLC cells. Notably, they did not display high toxicity in vitro against non-transformed cells (red blood cells, fibroblasts, bronchial epithelial cells, cardiomyocytes, and endothelial cells). Both compounds induced vasorelaxation and reduced endothelial cell migration, suggesting potential anti-angiogenic properties. RT151 confirmed its efficacy against NSCLC xenografts resistant to cisplatin. Either alone or combined with low doses of cisplatin, RT151 showed a good biodistribution profile in the liver, kidney, spleen, lung, and tumor. Hematochemical analysis and post-mortem organ pathology confirmed the safety of the compound in vivo, also when combined with cisplatin. To sum up, we have confirmed the effectiveness of a novel class of drugs against cisplatin-resistant NSCLC. Additionally, the compounds have a good biocompatibility and safety profile.

The First Brazilian Cardiovascular Registry of Atrial Fibrillation: Primary Results of the RECALL Study.

BACKGROUND: It is estimated that atrial fibrillation (AF) affects approximately 1.5 million people in Brazil; however, epidemiological data are limited. We sought to evaluate the characteristics, treatment patterns, and clinical outcomes in patients with AF in Brazil by creating the first nationwide prospective registry. METHODS: RECALL was a multicenter, prospective registry that included and followed for 1 year 4,585 patients with AF at 89 sites across Brazil from April 2012 to August 2019. Patient characteristics, concomitant medication use, and clinical outcomes were analyzed using descriptive statistics and multivariable models. RESULTS: Of 4,585 patients enrolled, the median age was 70 (61, 78) years, 46% were women, and 53.8% had permanent AF. Only 4.4% of patients had a history of previous AF ablation and 25.2% had a previous cardioversion. The mean (SD) CHA2DS2-VASc score was 3.2 (1.6); median HAS-BLED score was 2 (2, 3). At baseline, 22% were not on anticoagulants. Of those taking anticoagulants, 62.6% were taking vitamin K antagonists and 37.4% were taking direct oral anticoagulants. The primary reasons for not using an oral anticoagulant were physician judgment (24.6%) and difficulty in controlling (14.7%) or performing (9.9%) INR. Mean (SD) TTR for the study period was 49.5% (27.5). During follow-up, the use of anticoagulants and INR in the therapeutic range increased to 87.1% and 59.1%, respectively. The rates/100 patient-years of death, hospitalization due to AF, AF ablation, cardioversion, stroke, systemic embolism, and major bleeding were 5.76 (5.12-6.47), 15.8 (14.6-17.0), 5.0 (4.4-5.7), 1.8 (1.4-2.2), 2.77 (2.32-3.32), 1.01 (0.75-1.36), and 2.21 (1.81-2.70). Older age, permanent AF, New York Heart Association class III/IV, chronic kidney disease, peripheral arterial disease, stroke, chronic obstructive pulmonary disease, and dementia were independently associated with increased mortality while the use of anticoagulant was associated with lower risk of death. CONCLUSIONS: RECALL represents the largest prospective registry of patients with AF in Latin America. Our findings highlight important gaps in treatment, which can inform clinical practice and guide future interventions to improve the care of these patients.

2023 HRS/EHRA/APHRS/LAHRS Expert Consensus Statement on Practical Management of the Remote Device Clinic.

Remote monitoring is beneficial for the management of patients with cardiovascular implantable electronic devices by impacting morbidity and mortality. With increasing numbers of patients using remote monitoring, keeping up with higher volume of remote monitoring transmissions creates challenges for device clinic staff. This international multidisciplinary document is intended to guide cardiac electrophysiologists, allied professionals, and hospital administrators in managing remote monitoring clinics. This includes guidance for remote monitoring clinic staffing, appropriate clinic workflows, patient education, and alert management. This expert consensus statement also addresses other topics such as communication of transmission results, use of third-party resources, manufacturer responsibilities, and programming concerns. The goal is to provide evidence-based recommendations impacting all aspects of remote monitoring services. Gaps in current knowledge and guidance for future research directions are also identified.

Evaluation of Semiautomatic and Deep Learning-Based Fully Automatic Segmentation Methods on [18F]FDG PET/CT Images from Patients with Lymphoma: Influence on Tumor Characterization.

The objective is to assess the performance of seven semiautomatic and two fully automatic segmentation methods on [18F]FDG PET/CT lymphoma images and evaluate their influence on tumor quantification. All lymphoma lesions identified in 65 whole-body [18F]FDG PET/CT staging images were segmented by two experienced observers using manual and semiautomatic methods. Semiautomatic segmentation using absolute and relative thresholds, k-means and Bayesian clustering, and a self-adaptive configuration (SAC) of k-means and Bayesian was applied. Three state-of-the-art deep learning-based segmentations methods using a 3D U-Net architecture were also applied. One was semiautomatic and two were fully automatic, of which one is publicly available. Dice coefficient (DC) measured segmentation overlap, considering manual segmentation the ground truth. Lymphoma lesions were characterized by 31 features. Intraclass correlation coefficient (ICC) assessed features agreement between different segmentation methods. Nine hundred twenty [18F]FDG-avid lesions were identified. The SAC Bayesian method achieved the highest median intra-observer DC (0.87). Inter-observers' DC was higher for SAC Bayesian than manual segmentation (0.94 vs 0.84, p < 0.001). Semiautomatic deep learning-based median DC was promising (0.83 (Obs1), 0.79 (Obs2)). Threshold-based methods and publicly available 3D U-Net gave poorer results (0.56 ≤ DC ≤ 0.68). Maximum, mean, and peak standardized uptake values, metabolic tumor volume, and total lesion glycolysis showed excellent agreement (ICC ≥ 0.92) between manual and SAC Bayesian segmentation methods. The SAC Bayesian classifier is more reproducible and produces similar lesion features compared to manual segmentation, giving the best concordant results of all other methods. Deep learning-based segmentation can achieve overall good segmentation results but failed in few patients impacting patients' clinical evaluation.

Data-driven agent-based modelling of incentives for carbon sequestration: The case of sown biodiverse pastures in Portugal.

Sown biodiverse permanent pastures rich in legumes (SBP) offset animal farming emissions due to their potential to sequester carbon. From 2009 to 2014 Portugal implemented a programme that provided payments to incentivize the adoption of SBP. However, no proper evaluation of its outcome was conducted. To address this gap, we develop an agent-based model (ABM) at the municipality level to study the adoption of SBP in Portugal and assess the outcome of the programme. We applied the first pure data-driven approach in agricultural land-use ABM, which relies on machine learning algorithms to define the agents' behavioural rules and capture their interaction with biophysical conditions. The ABM confirms that the program effectively expanded the adoption of SBP. However, our estimates indicate that the adoption rate in the absence of payments would have been higher than originally predicted. Furthermore, the existence of the program decreased the adoption rate after its conclusion. These findings underscore the importance of using reliable models and considering residual effects to properly design land use policies. The ABM developed in this study provides a basis for future research aimed at supporting the development of new policies to further promote the adoption of SBP.

Perceived cognitive functioning in breast cancer patients treated with chemotherapy compared to matched healthy women: Evidence from a Portuguese study.

AIM: Cognitive concerns are one of the most frequently reported symptoms by breast cancer survivors. This study aimed to evaluate perceived cognitive functioning in Portuguese women with breast cancer treated with chemotherapy. METHODS: A cross-sectional study enrolling 146 women (73 with breast cancer and 73 healthy) was conducted from August to October 2017, invited to participate through online dissemination. Participants completed self-reported questionnaires to collect sociodemographic and clinical data and assess perceived cognitive functioning and psychological adjustment variables (anxiety and depression). RESULTS: Compared to healthy women, women with breast cancer showed significantly lower scores on the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) subscales and higher levels of depression. Both groups showed significant negative correlations between perceived cognitive functioning and anxiety and depression. Health status and depression seem to better explain perceived cognitive functioning, with health status adding significantly more explained variance beyond sociodemographic and psychological adjustment variables. CONCLUSION: The current findings provide evidence for the existence of more cognitive complaints among Portuguese women with breast cancer, compared to healthy individuals. Anxiety, depression, age and education also explain perceived cognitive functioning. Considering that health status and psychological adjustment seem to significantly explain perceived cognitive functioning, special attention should be given by health-care professionals, including nurses, to designing clinical interventions for breast cancer patients to help manage cognitive impairment.

Meaning of Life Therapy: A Pilot Study of a Novel Psycho-Existential Intervention for Palliative Care in Cancer.

Intervention in Palliative Care aims to provide physical, psychosocial, and spiritual relief for patients and family members. Brief interventions with a psycho-existential approach have shown positive responses; however, cultural adaptations are needed. This pilot study aimed to develop the Meaning of Life Therapy (MLT), a novel psycho-existential intervention, rooted in the Dignity Therapy, Life Review, and Meaning-Centered Psychotherapy. MLT was culturally adapted to the Portuguese context to include questions about forgiveness, apology, reconciliation, farewell, and a legacy document, i.e., the Life Letter. Nine PC cancer patients answered a 14-question MLT protocol, intended to help patients find purpose and meaning in life. Eight themes emerged: Family, Preservation of Identity, Life Retrospective, Clinical Situation, Achievements, Socio-Professional Valorization, Forgiveness/Apology/Reconciliation, and Saying Goodbye. MLT has proved its ability to respond to the psycho-existential needs of PC patients. Further studies should be conducted to gain extensive knowledge of the effectiveness of culturally responsive interventions.

Attitudes of dentists toward maintaining, repairing, or replacing direct composite resin restorations.

This study aimed to report the reasons for replacement of direct composite resin restorations in dental practices in Brazil. The study used a convenience sample of 213 dentists. A questionnaire was developed from previously validated instruments and sent electronically to prospective participants. The questions pertained to professional characteristics; criteria most frequently used in determining whether a direct composite resin restoration warranted replacement; and respondents' choice of treatment options (maintain, repair, or replace the restoration) in various clinical scenarios based on FDI World Dental Federation evaluation criteria, which are categorized into 3 groups: esthetic, functional, and biological properties. The descriptive statistical analysis was conducted using percentage frequencies, and associations between variables were tested using chi-square tests (α = 0.05). According to 47.9% of respondents, staining was the esthetic property that most often warranted replacement. For the functional property, 53.8% of respondents reported that fracture of material and retention was the most important factor indicating the need for replacement. For the clinical scenarios, 41.7% of respondents chose restoration replacement when evaluating esthetic properties, 59.8% when evaluating functional properties, and 64.4% when evaluating biological properties. Replacement, rather than maintenance or repair, was the most frequently reported clinical decision, and the dentists' professional profiles influenced treatment recommendations, with specialists exhibiting a slightly lower frequency of recommendations for replacement of direct composite resin restorations.

Half-Sandwich Ru(p-cymene) Compounds with Diphosphanes: In Vitro and In Vivo Evaluation As Potential Anticancer Metallodrugs.

Ruthenium(II) complexes are currently considered attractive alternatives to the widely used platinum-based drugs. We present herein the synthesis and characterization of half-sandwich ruthenium compounds formulated as [Ru(p-cymene)(L)Cl][CF3SO3] (L = 1,1-bis(methylenediphenylphosphano)ethylene, 1; L = 1,1-bis(diphenylphosphano)ethylene, 2), which were characterized by elemental analysis, mass spectrometry, 1H and 31P{1H} NMR, UV-vis and IR spectroscopy, conductivity measurements and cyclic voltammetry. The molecular structures for both complexes were determined by single-crystal X-ray diffraction. Their cytotoxic activity was evaluated using the MTT assay against human tumor cells, namely ovarian (A2780) and breast (MCF7 and MDA-MB-231). Both complexes were active against breast adenocarcinoma cells, with complex 1 exhibiting a quite remarkable cytotoxicity in the submicromolar range. Interestingly, at concentrations equivalent to the IC50 values in the MCF7 cancer cells, complexes 1 and 2 presented lower cytotoxicity in normal human primary fibroblasts. The antiproliferative effects of 1 and 2 in MCF7 cells might be associated with the induction of reactive oxygen species (ROS), leading to a combined cell death mechanism via apoptosis and autophagy. Despite the fact that in vitro a partial intercalation between complexes and DNA was observed, no MCF7 cell cycle delay or arrest was observed, indicating that DNA might not be a direct target. Complexes 1 and 2 both exhibited a moderate to strong interaction with human serum albumin, suggesting that protein targets may be involved in their mode of action. Their acute toxicity was evaluated in the zebrafish model. Complex 1 (the most toxic of the two) exhibited a lethal toxicity LC50 value about 1 order of magnitude higher than any IC50 concentrations found for the cancer cell models used, highlighting its therapeutic relevance as a drug candidate in cancer chemotherapy.

Brief emotional screening in oncology: Specificity and sensitivity of the emotion thermometers in the Portuguese cancer population.

OBJECTIVE: This study aimed to determine the cutoff and the specificity and sensitivity of the Emotion Thermometers (ET) in a Portuguese sample of cancer patients. METHOD: A total of 147 patients (mean age = 49.2; SD = 12.6) completed the ET, the Brief Symptom Inventory (BSI), and the Subjective Experiences of Illness Suffering Inventory. Data were collected in a cancer support institution and in a major hospital in the North of Portugal. RESULT: The optimal cutoff for the Anxiety Thermometer was 5v6 (until 5 and 6 or more), which identified 74% of the BSI-anxiety cases and 70% of noncases. The Depression Thermometer cutoff was 4v5 (until 4 and 5 or more), which identified 85% of BSI-depression cases and 82% of noncases. Cutoff for the Anger Thermometer was 4v5 (until 4 and 5 or more), which identified 83% of BSI-hostility cases and 73% of noncases; for the Distress Thermometer, the optimal cutoff was 4v5 (until 4 and 5 or more), which identified 84% of the suffering cases and 73% of noncases. Finally, for the Help Thermometer, it was 3v4 (until 3 and 4 or more), which helped to identify 93% of the suffering cases and 64% of noncases. SIGNIFICANCE OF RESULTS: Results supported the Portuguese version of the ET as an important screening tool for identifying the emotional distress in cancer patients.

The impact of informal cancer caregiving: A literature review on psychophysiological studies.

Caregiving can be experienced as a stressful process, which can cause psychological and physical consequences. The combination of prolonged stress and the physical demands of caregiving may impair the physiological functioning of caregivers and increase the risk of health problems creating considerable stress in the life of caregivers regarding emotional, physical, social and financial areas. This literature review explored studies that used measures of the autonomic nervous system in caregivers of oncology patients such as electrodermal and cardiovascular (re)activity. The results revealed that caregivers had elevated stress levels and a serious autonomic imbalance that may, in the long term, trigger negative health consequences such as infectious diseases, cancer progression, cardiovascular disease and even premature death. The results showed the need to carry out preventive strategies in this population, in order to improve the autonomic profile of caregivers of cancer patients.

Methyl-cyclopentadienyl Ruthenium Compounds with 2,2'-Bipyridine Derivatives Display Strong Anticancer Activity and Multidrug Resistance Potential.

New ruthenium methyl-cyclopentadienyl compounds bearing bipyridine derivatives with the general formula [Ru(η5-MeCp)(PPh3)(4,4'-R-2,2'-bpy)]+ (Ru1, R = H; Ru2, R = CH3; and Ru3, R = CH2OH) have been synthesized and characterized by spectroscopic and analytical techniques. Ru1 crystallized in the monoclinic P21/ c, Ru2 in the triclinic P1̅, and Ru3 in the monoclinic P21/ n space group. In all molecular structures, the ruthenium center adopts a "piano stool" distribution. Density functional theory calculations were performed for all complexes, and the results support spectroscopic data. Ru1 and Ru3 were poor substrates of the main multidrug resistance human pumps, ABCB1, ABCG2, ABCC1, and ABCC2, while Ru2 displayed inhibitory properties of ABCC1 and ABCC2 pumps. Importantly, all compounds displayed a very high cytotoxic profile for ovarian cancer cells (sensitive and resistant) that was much more pronounced than that observed with cisplatin, making them very promising anticancer agents.

A cohort study of cardiac resynchronization therapy in patients with chronic Chagas cardiomyopathy.

Aims: Cardiac resynchronization therapy (CRT) is an established procedure for patients with heart failure. However, trials evaluating its efficacy did not include patients with chronic Chagas cardiomyopathy (CCC). We aimed to assess the role of CRT in a cohort of patients with CCC. Methods and results: This retrospective study compared the outcomes of CCC patients who underwent CRT with those of dilated (DCM) and ischaemic cardiomyopathies (ICM). The primary endpoint was all-cause mortality and the secondary endpoints were the rate of non-advanced New York Heart Association (NYHA) class 12 months after CRT and echocardiographic changes evaluated at least 6 months after CRT. There were 115 patients in the CCC group, 177 with DCM, and 134 with ICM. The annual mortality rates were 25.4%, 10.4%, and 11.3%, respectively (P < 0.001). Multivariate analysis adjusted for potential confounders showed that the CCC group had a two-fold [hazard ratio 2.34 (1.47-3.71), P < 0.001] higher risk of death compared to the DCM group. The rate of non-advanced NYHA class 12 months after CRT was significantly higher in non-CCC groups than in the CCC group (DCM 74.0% vs. ICM 73.9% vs. 56.5%, P < 0.001). Chronic Chagas cardiomyopathy and ICM patients had no improvement in the echocardiographic evaluation, but patients in the DCM group had an increase in left ventricular ejection fraction and a decrease in left ventricular end-diastolic diameter. Conclusion: This study showed that CCC patients submitted to CRT have worse prognosis compared to patients with DCM and ICM who undergo CRT. Studies comparing CCC patients with and without CRT are warranted.

Consolidating Regionalized Global Characterization Factors for Soil Organic Carbon Depletion Due to Land Occupation and Transformation.

Land occupation and transformation change soil organic carbon (SOC) stocks, which are a priority indicator for biotic production potential (BPP) in life cycle impact assessment (LCIA). SOC is a potential umbrella indicator for land use-related impacts, but global LCIA characterization models have never been sufficiently regionalized. Regeneration times required for the calculation of transformation impacts are unknown and can only be estimated through expert judgment or using additional assumptions. In this paper, we calculate global midpoint characterization factors (CF) for SOC depletion following land use and land use change using data from the European Soil Data Center with a resolution of 30 arc second. We used three possible calculation procedures to determine regeneration times: (1) estimations based on literature; (2) equal regeneration duration for all land uses; (3) equal regeneration rates for all land uses. We then propose an innovative approach for LCIA that combines all CFs in this paper as well as prior models using a spatial consolidation approach to arrive at a single set of CFs. We show that this procedure combines the strengths of each individual model and dilutes their shortcomings, and recommend the use of these consolidated CFs rather than individual sets of factors. For endpoints, we applied a nutrient replacement method using fertilizer input to compensate for organic matter depletion and obtained monetary CFs for SOC-related damages caused by land use on BPP.

Indications for lung resection surgery and lung transplant in South American children with cystic fibrosis.

The current available literature evaluating lung resection surgery and lung transplantation in children with cystic fibrosis (CF) was reviewed through a PubMed search and references from selected studies were additionally included. Pulmonary resections, i.e. lobectomy, segmentectomy, and pneumonectomy, are seldom performed in CF. The main indications, in patients with a forced expiratory volume in 1second (FEV1) that is greater than 30% predicted, are localized bronchiectasis/atelectasis, severe hemoptysis, and bronchopleural fistula refractory to medical management. The potential benefits are decreased symptoms and pulmonary exacerbations, and an improved quality of life. Pre and postoperative intensive care is mandatory for surgical candidates. The risk of death should be taken into account when the procedure is considered. Selection for lung transplantation (LTx) candidates in children with CF in South America follows the International Society for Heart and Lung Transplantation (ISHLT) criteria. When compared to adults with CF, a poorer survival rate after LTx in children with CF has been observed in the literature, as well as in our LTx center in Brazil, reasons for which are still unknown. The main complications after LTx in children are early and late acute rejection, and infections. LTx is a therapeutic option for eligible children with CF, fulfilling the lung transplant candidacy criteria, as post-transplant survival rates are increasingly improving due to better management of the transplanted patient.

Experience of Lung Transplantation in Patients with Lymphangioleiomyomatosis at a Brazilian Reference Centre.

INTRODUCTION: Lung transplantation (LT) is the standard of care for patients with advanced lung diseases, including lymphangioleiomyomatosis (LAM). LAM accounts for only 1% of all LTs performed in the international registry. As a result, the global experience, including the use of mechanistic target of rapamycin (mTOR) inhibitors before and after LT in LAM, is still limited. METHODS: We conducted a retrospective review of all LAM patients who underwent LT at our centre between 2003 and 2016. Pre- and post-transplant data were assessed. RESULTS: Eleven women with LAM underwent LT, representing 3.3% of all procedures. Ten (91%) patients underwent double-LT. The mean age at diagnosis was 39 ± 6 years and the mean FEV1 before LT was 28 ± 14%. Only one patient underwent pleurodesis for recurrent pneumothorax. Pulmonary hypertension was confirmed in 3 (27%) patients. Four (36%) patients received sirolimus preoperatively; three of them received it until the day of LT, and there was no occurrence of bronchial anastomotic dehiscence after the procedure. Four patients (36%) received mTOR inhibitors post-transplant. The median follow-up from LT was 44 months. There were 3 deaths (27%) during the study and survival probabilities at 1, 3, and 5 years after LT were, 90, 90, and 77%, respectively. CONCLUSIONS: This data reinforces the role of LT for LAM patients with end-stage disease. The use of sirolimus seems to be safe before LT and the occurrence of complications after LT, including those LAM-related, should be continuously monitored.

Synthesis of disaccharides using ß-glucosidases from Aspergillus niger, A. awamori and Prunus dulcis.

OBJECTIVE: Glucose conversion into disaccharides was performed with ß-glucosidases from Prunus dulcis (ß-Pd), Aspergillus niger (ß-An) and A. awamori (ß-Aa), in reactions containing initial glucose of 700 and 900 g l-1. RESULTS: The reactions' time courses were followed regarding glucose and product concentrations. In all cases, there was a predominant formation of gentiobiose over cellobiose and also of oligosaccharides with a higher molecular mass. For reactions containing 700 g glucose l-1, the final substrate conversions were 33, 38, and 23.5% for ß-An, ß-Aa, and ß-Pd, respectively. The use of ß-An yielded 103 g gentiobiose l-1 (15.5% yield), which is the highest reported for a fungal ß-glucosidase. The increase in glucose concentration to 900 g l-1 resulted in a significant increase in disaccharide synthesis by ß-Pd, reaching 128 g gentiobiose l-1 (15% yield), while for ß-An and ß-Aa, there was a shift toward the synthesis of higher oligosaccharides. CONCLUSION: ß-Pd and the fungal ß-An and ß-Aa ß-glucosidases present quite dissimilar kinetics and selective properties regarding the synthesis of disaccharides; while ß-Pd showed the highest productivity for gentiobiose synthesis, ß-An presented the highest specificity.

How Well Does LCA Model Land Use Impacts on Biodiversity?--A Comparison with Approaches from Ecology and Conservation.

The modeling of land use impacts on biodiversity is considered a priority in life cycle assessment (LCA). Many diverging approaches have been proposed in an expanding literature on the topic. The UNEP/SETAC Life Cycle Initiative is engaged in building consensus on a shared modeling framework to highlight best-practice and guide model application by practitioners. In this paper, we evaluated the performance of 31 models from both the LCA and the ecology/conservation literature (20 from LCA, 11 from non-LCA fields) according to a set of criteria reflecting (i) model completeness, (ii) biodiversity representation, (iii) impact pathway coverage, (iv) scientific quality, and (v) stakeholder acceptance. We show that LCA models tend to perform worse than those from ecology and conservation (although not significantly), implying room for improvement. We identify seven best-practice recommendations that can be implemented immediately to improve LCA models based on existing approaches in the literature. We further propose building a "consensus model" through weighted averaging of existing information, to complement future development. While our research focuses on conceptual model design, further quantitative comparison of promising models in shared case studies is an essential prerequisite for future informed model choice.

Assessing biodiversity loss due to land use with Life Cycle Assessment: are we there yet?

Ecosystems are under increasing pressure from human activities, with land use and land-use change at the forefront of the drivers that provoke global and regional biodiversity loss. The first step in addressing the challenge of how to reverse the negative outlook for the coming years starts with measuring environmental loss rates and assigning responsibilities. Pinpointing the global pressures on biodiversity is a task best addressed using holistic models such as Life Cycle Assessment (LCA). LCA is the leading method for calculating cradle-to-grave environmental impacts of products and services; it is actively promoted by many public policies, and integrated as part of environmental information systems within private companies. LCA already deals with the potential biodiversity impacts of land use, but there are significant obstacles to overcome before its models grasp the full reach of the phenomena involved. In this review, we discuss some pressing issues that need to be addressed. LCA mainly introduces biodiversity as an endpoint category modeled as a loss in species richness due to the conversion and use of land over time and space. The functional and population effects on biodiversity are mostly absent due to the emphasis on species accumulation with limited geographic and taxonomical reach. Current land-use modeling activities that use biodiversity indicators tend to oversimplify the real dynamics and complexity of the interactions of species among each other and with their habitats. To identify the main areas for improvement, we systematically reviewed LCA studies on land use that had findings related to global change and conservation ecology. We provide suggestion as to how to address some of the issues raised. Our overall objective was to encourage companies to monitor and take concrete steps to address the impacts of land use on biodiversity on a broader geographical scale and along increasingly globalized supply chains.

Evidence for cardiac safety and antiarrhythmic potential of chloroquine in systemic lupus erythematosus.

AIMS: To perform a comprehensive evaluation of heart rhythm disorders and the influence of disease/therapy factors in a large systemic lupus erythematosus (SLE) cohort. METHODS AND RESULTS: Three hundred and seventeen consecutive patients of an ongoing electronic database protocol were evaluated by resting electrocardiogram and 142 were randomly selected for 24 h Holter monitoring for arrhythmia and conduction disturbances. The mean age was 40.2 ± 12.1 years and disease duration was 11.4 ± 8.1 years. Chloroquine (CQ) therapy was identified in 69.7% with a mean use of 8.5 ± 6.7 years. Electrocardiogram abnormalities were detected in 66 patients (20.8%): prolonged QTc/QTd (14.2%); bundle-branch block (2.5%); and atrioventricular block (AVB) (1.6%). Age was associated with AVB (P = 0.029) and prolonged QTc/QTd (P = 0.039) whereas anti-Ro/SS-A and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were not (P > 0.05). Chloroquine was negatively associated with AVB (P = 0.01) as was its longer use (6.1 ± 6.9 vs. 1.0 ± 2.5 years, P = 0.018). Time of CQ use was related with the absence of AVB [odds ratio (OR) = 0.103; 95% confidence interval (CI) = 0.011-0.934, P = 0.043] in multiple logistic regression. Holter monitoring revealed abnormalities in 121 patients (85.2%): supraventricular ectopies (63.4%) and tachyarrhythmia (18.3%); ventricular ectopies (45.8%). Atrial tachycardia/fibrillation (AT/AF) were associated with shorter CQ duration (7.05 ± 7.99 vs. 3.63 ± 5.02 years, P = 0.043) with a trend to less CQ use (P = 0.054), and older age (P < 0.001). Predictors of AT/AF in multiple logistic regression were age (OR = 1.115; 95% CI = 1.059-1.174, P < 0.001) and anti-Ro/SS-A (OR = 0.172; 95% CI = 0.047-0.629, P = 0.008). CONCLUSIONS: Chloroquine seems to play a protective role in the unexpected high rate of cardiac arrhythmias and conduction disturbances observed in SLE. Further studies are necessary to determine if this antiarrhythmic effect is due to the disease control or a direct effect of the drug.