Green synthesis of ethyl cinnamates under microwave irradiation: photophysical properties, cytotoxicity, and cell bioimaging.

A simple and green method for the synthesis of six ethyl cinnamates was performed via Horner-Wadsworth-Emmons reaction under microwave irradiation. The photoluminescent properties of all compounds in ethyl acetate solutions were evaluated demonstrating that all compounds exhibit fluorescence. Five compounds exhibited blue emissions in the 369-442 nm range, and another compound exhibited blue-green emission at 504 nm. This last compound showed the largest Stokes shift (134 nm), and the highest quantum yield (17.8%). Two compounds showed extinction coefficient values (ε) higher than 30 000 M-1 cm-1, which are appropriate for cell bioimaging applications. In this sense, cytotoxicity assays were performed using Vero cells at different concentrations; the results showed that these compounds were not cytotoxic at the highest concentration tested (20 µg mL-1). Finally, the analysis by fluorescence microscopy for localization and cellular staining using Vero cells demonstrated that the compounds stained the cytoplasm and the nuclei in a selective way.

Unnecessary thyroid surgery rate for suspicious nodule in the absence of molecular testing.

Background: Molecular tests for suspicious thyroid nodules decrease rates of unnecessary surgeries but are not widely used due to reimbursement issues. The aim of this study was to assess the rate of unnecessary surgery performed in real-life setting for Bethesda III, IV and V nodules in the absence of molecular testing. Method: This is a single-center retrospective study of consecutive patients undergoing fine needle aspiration cytology (FNAC) with rapid on-site evaluation between January 2017 and December 2021. Unnecessary surgery was defined as surgery performed because of Bethesda III, IV, or V results in the absence of local compressive symptoms with final benign pathology and as second surgery for completion thyroidectomy. Results: In the 862 patients (640 females, mean age: 54.2 years), 1010 nodules (median size: 24.4 mm) underwent 1189 FNAC. Nodules were EU-TIRADS 2, 3, 4, and 5 in 3%, 34%, 42%, and 22% of cases, respectively. FNAC was Bethesda I, II, III, IV, V, and VI in 8%, 48%, 17%, 17%, 3%, and 6%, respectively. Surgery was performed in 36% of Bethesda III nodules (benign on pathology: 81%), in 74% of Bethesda IV nodules (benign on pathology: 76%) and in 97% of Bethesda V nodules (benign on pathology: 21%). Surgery was considered unnecessary in 56%, 68%, and 21% of patients with Bethesda III, IV, and V nodules, respectively. Conclusion: In this real data cohort surgery was unnecessary in more than half of patients with Bethesda III and IV nodules and in 21% of patients with Bethesda V nodules.

Microwave-Assisted Synthesis of Aminophosphonic Derivatives and Their Antifungal Evaluation against Lomentospora prolificans.

Lomentospora prolificans is a pathogenic and multidrug-resistant fungus that can infect both immunocompetent and immunocompromised patients, with mortality rates up to 87%. The World Health Organization (WHO) included this fungal species in its first list of 19 priority fungal pathogens, which focused on fungal pathogens that can cause invasive acute and subacute systemic fungal infections. Therefore, there is a growing interest in finding new therapeutic alternatives. In this work, the synthesis of twelve α-aminophosphonates by the microwave-assisted Kabachnik-Fields reaction and twelve α-aminophosphonic acids by a monohydrolysis reaction is reported. All compounds were evaluated by the agar diffusion method as a preliminary screening in comparison with voriconazole, showing inhibition halos for compounds 7, 11, 13, 22 and 27. The five active compounds in the preliminary tests were evaluated against five strains of L. prolificans following protocol M38-A2 from CLSI. The results showed that these compounds exhibit antifungal activity in the concentration range of 900->900 µg/mL. Cytotoxicity against healthy COS-7 cells was also evaluated by the MTT assay, and it was shown that compound 22 was the least cytotoxic, with a viability of 67.91%, comparable to the viability exhibited by voriconazole (68.55%). Docking studies showed that the possible mechanism of action of the active compounds could be through the inhibition of the enzyme lanosterol-14-alpha-demethylase in an allosteric hydrophobic cavity.

Immunotherapies: How Do They Work?

The understanding of the immune system and the discovery of the proteins and processes involved in its regulation have enabled the emergence of new approaches against cancer. The development of antibodies (immune checkpoint inhibitors) able of blocking interactions that suppress the activation of T cells or their effector actions against cancer cells has modified the prognosis of several cancer forms. Bispecific antibodies as well as cellular immunotherapies (CARs/TILs) are new immunotherapy approaches that have already shown their effectiveness in certain onco-haematological diseases. Unfortunately, only a fraction of treated patients derives benefit from these treatments. The future challenge will be to understand the resistance mechanisms to immunotherapies so that treatment may be personalized for each patient.

Endocrine and Neurological Toxicities of Immunotherapies.

Immunotherapy has revolutionized cancer care but exposes patients to a new spectrum of complications that mimic autoimmune diseases, which are referred to as immune-related adverse events (irAEs). Endocrine complications are among the most common and involve nearly all endocrine tissues. Corticosteroids are not useful in endocrine irAEs, and definitive hormonal substitution is often indicated. Neurological irAEs can involve the central nervous system, the peripheral nervous system or the neuromuscular junction. Neurological irAEs are among the rarer complications but are associated with a higher morbidity and fatality. Therefore, prompt recognition and treatment are crucial. In this article, we discuss incidence, presentation, work-up, management, and common pitfalls in endocrine and neurological irAEs.

Angiogenic biomarkers for the follow-up of singleton pregnancies with suspected preeclampsia.

BACKGROUND: Preeclampsia (PE) is a hypertensive disorder of pregnancy and one of the leading causes of maternal and fetal morbidity and mortality worldwide. While the underlying cause of remains unknown, abnormal placentation in early stages of pregnancy is thought to be a main triggering event for the more severe and early-onset forms. A consequence of placental insufficiency is an imbalance of angiogenic factors in the maternal circulation. The objective was to assess the utility of the angiogenic biomarker sFlt-1/PlGF for the diagnosis, follow-up and prognosis of preeclampsia. METHODS: This was a retrospective cohort study based including 65 consecutive singleton pregnancies with suspected preeclampsia referred to our hospital between January 2018 and February 2019. PE was defined as early-onset (20-33+6 weeks) and late-onset (≥34 weeks). The main independent variable was sFlt-1/PlGF classified in women with early or late onset PE, respectively, as low when <38 or <38, intermediate when 38-84 or 38-109, and high when ≥85 or ≥110. RESULTS: PE was confirmed in 14 (4 early-onset, 10 late-onset) of the participants. 122 sFlt-1/PIGF ratio determinations were requested. The optimal sFlt-1/PlGF to predict PE was ≥86 with a sensitivity of 93% and a specificity of 96% (AUC 0.95; CI 95% 0.90-1.0; P<0.001). A multilevel logistic model for the diagnosis of PE was adjusted for age, Body Mass Index, diabetes, proteinuria and mean arterial pressure. Women were 16.5 times (P=0.013) more likely to develop PE if they had intermediate sFlt-1/PlGF levels and 451 times (P<0.001) more likely if they had high biomarker levels compared to those with levels below 38. The probability of PE was 3.73 times (P=0.046) greater in those with maternal and/or fetal complications. CONCLUSIONS: The biomarker proved useful to diagnose PE and assess its prognosis. Patients diagnosed with PE had a higher frequency of complications and their newborns were of lower birth weight.

Unexpected impairment of INa underpins reentrant arrhythmias in a knock-in swine model of Timothy syndrome.

Timothy syndrome 1 (TS1) is a multi-organ form of long QT syndrome associated with life-threatening cardiac arrhythmias, the organ-level dynamics of which remain unclear. In this study, we developed and characterized a novel porcine model of TS1 carrying the causative p.Gly406Arg mutation in CACNA1C, known to impair CaV1.2 channel inactivation. Our model fully recapitulated the human disease with prolonged QT interval and arrhythmic mortality. Electroanatomical mapping revealed the presence of a functional substrate vulnerable to reentry, stemming from an unforeseen constitutional slowing of cardiac activation. This signature substrate of TS1 was reliably identified using the reentry vulnerability index, which, we further demonstrate, can be used as a benchmark for assessing treatment efficacy, as shown by testing of multiple clinical and preclinical anti-arrhythmic compounds. Notably, in vitro experiments showed that TS1 cardiomyocytes display Ca2+ overload and decreased peak INa current, providing a rationale for the arrhythmogenic slowing of impulse propagation in vivo.

Fibroblast growth factor receptor (FGFR) inhibitor rogaratinib in patients with advanced pretreated squamous-cell non-small cell lung cancer over-expressing FGFR mRNA: The SAKK 19/18 phase II study.

BACKGROUND: Patients with advanced squamous-cell lung cancer (SQCLC) frequently (46%) exhibit tumor overexpression of fibroblast growth factor receptor (FGFR) messenger ribonucleic acid (mRNA). Rogaratinib is a novel oral pan-FGFR inhibitor with a good safety profile and anti-tumor activity in early clinical trials as a single agent in FGFR pathway-addicted tumors. SAKK 19/18 determined clinical activity of rogaratinib in patients with advanced SQCLC overexpressing FGFR1-3 mRNA. METHODS: Patients with advanced SQCLC failing standard systemic treatment and with FGFR1-3 mRNA tumor overexpression as defined in the protocol received rogaratinib 600 mg BID until disease progression or intolerable toxicity. A 6-months progression-free survival rate (6mPFS) ≤15 % was considered uninteresting (H0), whereas a 6mPFS ≥38 % was considered promising (H1). According to a Simon 2-stage design, 2 out of 10 patients of the first stage were required to be progression-free at 6 months. Comprehensive Genomic Profiling was performedusing the Oncomine Comprehensive Assay Plus (Thermo Fisher Scientific). RESULTS: Between July 2019 and November 2020, 49 patients were screened and 20 were classified FGFR-positive. Among a total of 15 patients, 6mPFS was reached in 1 patient (6.7 %), resulting in trial closure for futility after the first stage. There were 7 (46.7 %) patients with stable disease and 5 (33.3 %) patients with progressive disease. Median PFS was 1.6 (95 % CI 0.9-3.5) months and median overall survival (OS) 3.5 (95 % CI 1.0-5.9) months. Most frequent treatment-related adverse events (TRAEs) included hyperphosphatemia in 8 (53 %), diarrhea in 5 (33 %), stomatitis in 3 (20 %) and nail changes in 3 (20 %) patients. Grade ≥3 TRAEs occurred in 6 (40 %) patients. No associations between mutational profile and treatment outcome were observed. CONCLUSION: Despite preliminary signals of activity, rogaratinib failed to improve PFS in patients with advanced SQCLC overexpressing FGFR mRNA. FGFR inhibitors in SQCLC remain a challenging field, and more in-depth understanding of pathway crosstalks may lead to the development of drug combinations with FGFR inhibitors resulting in improved outcomes.

Novel α-Aminophosphonates and α-Aminophosphonic Acids: Synthesis, Molecular Docking and Evaluation of Antifungal Activity against Scedosporium Species.

The Scedosporium genus is an emerging pathogen with worldwide prevalence and high mortality rates that gives multidrug resistance to antifungals; therefore, pharmacological alternatives must be sought for the treatment of diseases caused by this fungus. In the present project, six new α-aminophosphates were synthesized by the Kabachnik-Fields multicomponent reaction by vortex agitation, and six new monohydrolyzed α-aminophosphonic acids were synthesized by an alkaline hydrolysis reaction. Antifungal activity was evaluated using the agar diffusion method as an initial screening to determine the most active compound compared to voriconazole; then it was evaluated against 23 strains of the genus Scedosporium following the M38-A2 protocol from CLSI (activity range: 648.76-700 µg/mL). Results showed that compound 5f exhibited the highest antifungal activity according to the agar diffusion method (≤1 mg/mL). Cytotoxicity against healthy COS-7 cells was also evaluated by the MTT assay and it was shown that compound 5f exhibits a lower toxicity in comparison to voriconazole at the same concentration (1000 µM). A docking study was conducted afterwards, showing that the possible mechanism of action of the compound is through the inhibition of allosteric 14-α-demethylase. Taking these results as a basis, 5f is presented as a compound with attractive properties for further studies.

[Does high-dose intravenous vitamin C has anti-cancer activity ?] / La vitamine C haute dose intraveineuse a-t-elle un effet antitumoral ?

High-dose intravenously (i.v) vitamin C in cancer patients is controversial. Numerous studies carried out on cancer cell lines and animal models demonstrated that millimolar vitamin C concentrations inhibit tumor cells viability, especially in association with chemotherapy. In cancer patients, high-dose i.v vitamin C in monotherapy does not show any anti-cancer activity. Clinical trials assessing high-dose i.v vitamin C concomitantly with chemotherapy do not conclude to reliable evidence for tumor control or overall survival benefit. Randomized double-blind trials are warranted.

La vitamine C administrée par voie intraveineuse (IV) chez les patients atteints de cancer est controversée. De nombreux travaux effectués sur des lignées cellulaires cancéreuses et des modèles animaux montrent que des concentrations plasmatiques pharmacologiques (≥ 15 mmol/l) de vitamine C sont capables de diminuer la viabilité des cellules cancéreuses. Chez les patients atteints de cancer, l'administration d'une haute dose IV de vitamine C seule ne montre pas de signe d'activité antitumorale. Elle a également été étudiée en association avec de la chimiothérapie, mais les essais cliniques réalisés ne permettent pas de conclure à un bénéfice pour les patients en termes de contrôle de la maladie oncologique ou de survie. Des études randomisées contre placebo et en double aveugle sont indispensables.

Long-term follow-up for childhood cancer survivors: the Geneva experience.

AIMS OF THE STUDY: Although the 5-year survival for pediatric cancer in Switzerland today is over 85%, two thirds of the survivors will develop chronic health conditions due to the disease or to the toxicity of treatments. In this context, a long-term personalized follow-up program (LTFU program), was set up at the University Hospitals of Geneva (HUG) since 2015. We aimed to describe this program, more particularly the specialized follow-ups set up, the cumulative burden of the chronic health conditions, and finally assess the satisfaction of patients and/or their parents with it. METHODS: A monocentric retrospective study was performed where data on follow-ups and chronic health conditions were collected from medical charts of people who had childhood cancer and who participated in the LTFU program. Chronic health conditions were classified and graded in severity with the Common Terminology Criteria of Adverse Events (CTCAE) classification, version 5.0. This study was completed by a satisfaction survey among patients and/or their parents. RESULTS: Out of 83 eligible patients, 51 (61.4%) accepted to participate, with an average age of 17.4 years (range, 10 to 35) at the time of study. Mean delay since end of treatment was 9.8 years (range: 4.5-31). The prevalence of any chronic health condition is 82.3%, 43.1% for having 1 or 2 chronic health conditions and 39.2% for having more than 3 chronic health conditions. The total number of Grade CTCAE 1-4 chronic health conditions was 118 for the 51 participants, with a mean of 2.3 (range, 0 to 7) disorders per patient. The most frequently affected systems were neurological (14.4%), musculoskeletal (13.6%), endocrine (9.3%) and renal (9.3%) systems. Sarcoma, central nervous system tumors and neuroblastoma were the diagnoses associated with the highest average number of chronic health conditions. Among the 118 questionnaires sent to patients and/or parents, we received 82 (69.5%) responses. The level of satisfaction was good to excellent for more than 90% of the participants, for all the items evaluated. CONCLUSIONS: Childhood cancer survivors present a significant number of chronic health conditions, confirming the need for appropriate long-term, multidisciplinary and patient-specific medical follow-up based on the primary diagnosis and therapies received. Moreover, the LTFU program at the HUG was highly appreciated by patients and/or their parents and this motivates its permanent conduct.

Synthesis of ɑ,ß-Unsaturated Benzotriazolyl-1,3,4-Oxadiazole Derivatives: Anticancer Activity, Cytotoxicity, and Cell Imaging.

A series of ten α , ß -unsaturated benzotriazolyl-1,3,4-oxadiazole derivatives was synthesized and all compounds were evaluated in vitro against three breast cancer cell lines (MCF-7, MDA-MB-231 and 4T1) at different concentrations (0.1, 0.5, 1, 2, 3, 4 and 5 mg/mL). The results showed that compounds 6a, 6c, 6d, 6f, 6g, and 6i displayed acceptable anticancer activity, where compound 6f was the most active on the three cell lines (IC50 = 0.80, 0.07, and 0.30 mg/mL, respectively). Regarding the cytotoxicity assay, the compounds exhibited modest toxicity on murine splenocytes and peripheral human blood cells at the highest concentration tested (5 mg/mL). Compound 6f was further evaluated at different concentrations showing moderate cytotoxicity at the 5 mg/mL concentration and negligible cytotoxicity at the minimum concentration evaluated (0.05 mg/mL). Finally, the compounds 6a, 6c, 6d, 6f, 6g, 6i, and 6j were evaluated as fluorescence markers due to their ability to be internalized into MCF-7 cells.

Sobrecarga y calidad de vida en cuidadoras de pacientes oncológicos al inicio de los cuidados paliativos. Estudio CUIDPALCOSTASOL / Burden and quality of life in caregivers of cancer patients at the beginning of palliative care. CUIDPALCOSTASOL Study

Objetivos: Describir la calidad de vida y sobrecarga de las cuidadoras familiares de pacientes oncológicos al inicio de los cuidados paliativos. Método: Estudio descriptivo transversal en la cohorte CUIDPACOSTASOL de cuidadoras familiares de pacientes con cáncer en fase paliativa incluidos entre febrero de 2017 y diciembre de 2019, de centros de salud del Distrito de Atención Primaria Costa del Sol y Málaga-Valle del Guadalhorce, y Fundación Cudeca. Se recogieron datos sociodemográficos de cuidadoras y pacientes, y se aplicaron cuestionarios específicos para medir la sobrecarga y satisfacción familiar (Zarit y FAMCARE), calidad de vida (SF-36) y diagnósticos enfermeros (NANDA), así como las características del paciente (PPI, PPSv2). Resultados: Se incluyó a 174 personas cuidadoras familiares, de las cuales el 86,8% eran mujeres con una edad media de 57 años. El 60,6% percibía su salud como buena y la puntuación media en la escala de Zarit fue 13,0. El diagnóstico enfermero (NANDA) más repetido fue «Riesgo de cansancio del rol del cuidador» (41,8%). Las dimensiones de calidad de vida con mayor puntuación fueron «Función física» (80,5), y «Rol físico» (67,2). El 62,6% de las personas cuidadas eran hombres con una edad media de 73 años, y requerían cuidados con una media de 19 horas al día. La puntuación media en la Escala Funcional Paliativa PPSv2 fue de 44,9% y en el Índice de pronóstico paliativo PPI, 3,9%. Conclusiones: Las cuidadoras familiares de este estudio presentaban sobrecarga moderada, alto riesgo de cansancio del rol de cuidador, y aceptables salud percibida y calidad de vida. Es probable que esto se deba a que estaban en el inicio de los cuidados paliativos.(AU)

Objectives: To describe the quality of life and caregiver burden of family caregivers of cancer patients at the beginning of palliative care. Method: Cross-sectional descriptive study in the CUIDPACOSTASOL cohort of family caregivers of palliative phase cancer patients, included between February 2017 and December 2019 from health centres of the Costa del Sol and Malaga-Valle del Guadalhorce Primary Care District, and Cudeca Foundation. Sociodemographic data on caregivers and patients, specific questionnaires related to family caregiver burden as well as satisfaction (Zarit and FAMCARE), quality of life (SF-36) and nursing diagnoses (NANDA), and patient characteristics (PPI, PPSv2) were collected. Results: 174 family caregivers were included, 86.8% were women with a mean age of 57 years. 60.6% perceived their health as good, and the mean score on the Zarit scale was 13.0. The most repeated nursing diagnosis (NANDA) was «Risk for caregiver role strain» (41.8%). The quality-of-life dimensions with the highest scores were «Physical function» (80.5), and «Physical role» (67.2). Of the people receiving care, 62.6% were men with a mean age of 73 years and required care for an average of 19 hours per day. The mean score on the Palliative Performance Scale, PPSv2, was 44.9%, and 3.9% on the PPI Palliative Prognostic Index. Conclusions: Family caregivers in this study had moderate burden, high risk for caregiver role strain, and acceptable perceived health and quality of life. This is probably because they were at the beginning of palliative care.(AU)

Burden and quality of life in caregivers of cancer patients at the beginning of palliative care. CUIDPALCOSTASOL Study.

OBJECTIVES: To describe the quality of life and caregiver burden of family caregivers of cancer patients at the beginning of palliative care. METHOD: Cross-sectional descriptive study in the CUIDPACOSTASOL cohort of family caregivers of palliative phase cancer patients, included between February 2017 and December 2019 from health centres of the Costa del Sol and Malaga-Valle del Guadalhorce Primary Care District, and Cudeca Foundation. Sociodemographic data on caregivers and patients, specific questionnaires related to family caregiver burden as well as satisfaction (Zarit and FAMCARE), quality of life (SF-36) and nursing diagnoses (NANDA), and patient characteristics (PPI, PPSv2) were collected. RESULTS: 174 family caregivers were included, 86.8% were women with a mean age of 57 years. 60.6% perceived their health as good, and the mean score on the Zarit scale was 13.0. The most repeated nursing diagnosis (NANDA) was «Risk for caregiver role strain¼ (41.8%). The quality-of-life dimensions with the highest scores were «Physical function¼ (80.5), and «Physical role¼ (67.2). Of the people receiving care, 62.6% were men with a mean age of 73 years and required care for an average of 19 h per day. The mean score on the Palliative Performance Scale, PPSv2, was 44.9%, and 3.9% on the PPI Palliative Prognostic Index. CONCLUSIONS: Family caregivers in this study had moderate burden, high risk for caregiver role strain, and acceptable perceived health and quality of life. This is probably because they were at the beginning of palliative care.

Redefining cancer of unknown primary: Is precision medicine really shifting the paradigm?

The concept of Cancer of Unknown Primary (CUP) has evolved with the advent of medical oncology. CUP can be difficult to diagnose and represents 2 to 5% of new cancers, therefore not exceptionally rare. Within CUPs can be identified a subset of favourable prognosis tumours, however the vast majority of CUP patients belongs to a poor prognosis group. CUP features significant oncological challenges, such as unravelling biological and transversal issues, and most importantly, improving patient's outcomes. In that regard, CUP patients' outcomes regrettably showed minimal improvement for decades and CUP remains a cancer group of very poor prognosis. The biology of CUP has two main hypotheses. One is that CUP is a subgroup of a given primary cancer, where the primary is present but cannot be seen due to its small size. The other, the "true" CUP hypothesis, states that CUP share features that make them a specific entity, whatever their tissue of origin. A true biological signature has not yet been described, but chromosomal instability is a hallmark of poor prognosis CUP group. Precision oncology, despite achieving identifying the putative origin of the CUP, so far failed to globally improve outcomes of patients. Targeting molecular pathways based on molecular analysis in CUP management is under investigation. Immunotherapy has not shown ground-breaking results, to date. Accrual is also a crucial issue in CUP trials. Herein we review CUP history, biological features and remaining questions in CUP biology, the two main approaches of molecular oncology in CUP management, in order to draw perspectives in the enormous challenge of improving CUP patient outcomes.

Burden and quality of life in caregivers of cancer patients at the beginning of palliative care. CUIDPALCOSTASOL Study. / Sobrecarga y calidad de vida en cuidadoras de pacientes oncológicos al inicio de los cuidados paliativos. Estudio CUIDPALCOSTASOL.

OBJECTIVES: To describe the quality of life and caregiver burden of family caregivers of cancer patients at the beginning of palliative care. METHOD: Cross-sectional descriptive study in the CUIDPACOSTASOL cohort of family caregivers of palliative phase cancer patients, included between February 2017 and December 2019 from health centres of the Costa del Sol and Malaga-Valle del Guadalhorce Primary Care District, and Cudeca Foundation. Sociodemographic data on caregivers and patients, specific questionnaires related to family caregiver burden as well as satisfaction (Zarit and FAMCARE), quality of life (SF-36) and nursing diagnoses (NANDA), and patient characteristics (PPI, PPSv2) were collected. RESULTS: 174 family caregivers were included, 86.8% were women with a mean age of 57 years. 60.6% perceived their health as good, and the mean score on the Zarit scale was 13.0. The most repeated nursing diagnosis (NANDA) was «Risk for caregiver role strain¼ (41.8%). The quality-of-life dimensions with the highest scores were «Physical function¼ (80.5), and «Physical role¼ (67.2). Of the people receiving care, 62.6% were men with a mean age of 73 years and required care for an average of 19 hours per day. The mean score on the Palliative Performance Scale, PPSv2, was 44.9%, and 3.9% on the PPI Palliative Prognostic Index. CONCLUSIONS: Family caregivers in this study had moderate burden, high risk for caregiver role strain, and acceptable perceived health and quality of life. This is probably because they were at the beginning of palliative care.

Maternal and fetal outcomes during pregnancy and puerperium in obese and overweight pregnant women. A cohort study.

PURPOSE: compare incidences of maternal-fetal complications during pregnancy, labor, and early puerperium according to baseline BMI in a consecutive cohort of pregnant women. METHODS: This retrospective cohort study compares pregnancy outcome indicators by body mass index (BMI) in 1236 pregnant women managed over the period January 2017 to May 2018. Data were collected regarding the personal history (smoking, diabetes and hypertension), obstetrics and BMI (kg/m2) (normoweight 18.5-24.9, overweight 25-29.9, obese ≥ 30). RESULTS: Of the 1236 women, 354 (28.6%) were overweight and 206 (16.7%) were obese at the start of pregnancy follow-up. Mean age at this time was 33 years (SD 6). Risk factors for a cesarean-section delivery assessed through logistic regression were maternal age (OR 1.05 95% CI 2.06-6.15; p < 0.001) and previous C-section (OR 4.21 95% CI 2.89-6.14; p < 0.001) regardless of BMI. In a propensity score analysis, pregnancy weight gain was found lower in obese vs normoweight (- 2.73 kg 95% CI - 3.74 to - 1.72 p < 0.001), and newborn weight higher in obese vs normoweight women (161.21 g 95% CI 57.94-264.48 p = 0.002). Labor duration and weight gain were reduced in overweight vs normoweight subjects (- 0.72 h 95% CI - 1.27 to - 0.17 p = 0.010 and 0.81 kg 95% CI - 1.50 to - 0.12 p = 0.021, respectively). CONCLUSIONS: In this cohort, obese women showed higher rates of prenatal complications yet obesity and overweight were not related to worse puerperium outcomes.

Attitudinal beliefs concerning suicidal behavior among healthcare professionals in the Western Costa del Sol healthcare district (Spain).

Suicide continues to be the leading external cause of death in Spain, according to the latest report on deaths by cause of death published by the National Statistics Institute (INE, for its initials in Spanish) in December 20191. According to this report, there were 3,539 deaths by suicide recorded in 2018. Ten people voluntarily ending their lives each day. Málaga province recorded 134 deaths by suicide in 2018, being therefore one of the provinces with the highest incidence in the autonomous community of Andalucía and the eighth nationally.

Creencias actitudinales sobre laconducta suicida en profesionalessanitarios del área sanitaria de laCosta del Sol Occidental / Attitudinal beliefs about suicidal suicidal behavior in health professionals health professionals in the health area of the Western Costa del Sol

Introducción: El suicidio sigue siendo la primera causa demuerte externa en España como describe el último informede defunciones según la causa de muerte publicada por elInstituto Nacional de Estadística (INE) en diciembre de 20191.Según este informe los fallecimientos por suicidio registrados en el año 2018 se situaron en 3.539 fallecimientos. Diezpersonas se quitan la vida de forma voluntaria diariamente.La provincia de Málaga registró 134 muertes por suicidio enel mismo año, siendo por tanto una de las provincias conmayor incidencia en la comunidad autónoma de Andalucíay la octava a nivel nacional.Metodología. La muestra del estudio fueron de 135 profesionales. Se trata de un estudio transversal descriptivo deperiodo mediante encuesta, realizado entre los profesionales sanitarios de un Área Sanitaria de Málaga. Las creenciasactitudinales fueron valoradas a través del Cuestionariode Creencias Actitudinales sobre Comportamiento Suicida(CCCS-18) que incluye cuatro factores: legitimización delsuicidio, suicidio en enfermos terminarles, dimensión moraly propio suicidio, medidas con una escala de respuesta enpromedio de 1 a 7 puntos, identificando creencias estigmatizantes aquellas puntuaciones promedias inferiores a 3,5.Resultados. Un total de 135 profesionales completaronel cuestionario, siendo un 58,5 % enfermeras, 25,9 % facultativos y 15,6 % trabajadores sociosanitarios. La puntuaciónmedia de la escala CCCS-18 fue de 3,6 (DE: 1,17) puntos,hallándose diferencias significativas en función de la profesión (p: 0,043), con una media 3,22 (DE: 1,17) en facultativos,3,66 (DE: 1,02) en enfermeras y 3,99 (DE: 1,52) en trabajadores sociosanitarios. En análisis por factores, se hallaronpuntuaciones promedias en la muestra inferior a 3,5, tantoen factor “legitimación del suicidio” (media: 2,59; DE: 1,28),como en factor “propio suicidio” (media: 2,9; DE: 1,47).Conclusiones. (AU)

Introduction: Suicide continues to be the leading external cause of death in Spain, according to the latest report ondeaths by cause of death published by the National StatisticsInstitute (INE, for its initials in Spanish) in December 20191.According to this report, there were 3,539 deaths by suiciderecorded in 2018. Ten people voluntarily ending their liveseach day. Málaga province recorded 134 deaths by suicide in2018, being therefore one of the provinces with the highestincidence in the autonomous community of Andalucía andthe eighth nationally.Method. This descriptive, cross-sectional period-prevalencesurvey of health professionals was carried out in one MálagaHealthcare Area (Spain). The main outcome variable was attitudinal beliefs, which were evaluated using the Questionnaire onAttitudinal Beliefs towards Suicide Behavior (CCCS-18), whichincludes four factors: legitimization of suicide, suicide in terminating patients, moral dimension and suicide itself, measuredwith an average response scale of 1 to 7 points, identifying stigmatizing attitudes or beliefs those average scores lower than 3.5.Results. A total of 135 health professionals completedthe questionnaire, being 58.5% nurses, 25.9% doctors and15.6% social health workers. The mean score of the CCCS-18scale was 3.6 (SD: 1.17) points, finding significant differences depending on the profession (p: 0.043), with a mean 3.22(SD: 1.17) in physicians, 3.66 (SD: 1.02) in nurses, and 3.99(SD: 1.52) in social health workers. In analysis by factors,mean scores were found in the sample below 3.5 both in thefactor “legitimation of suicide” (mean: 2.59; SD: 1.28), andin the factor “own suicide” (mean: 2 , 9; SD: 1.47). (AU)

Synthesis and in vitro evaluation of antimycobacterial and cytotoxic activity of new α,ß-unsaturated amide, oxazoline and oxazole derivatives from l-serine.

The synthesis of 19 compounds derived from l-serine and analogs of p-substituted cinnamic acid is reported. Oxazolines 9 and oxazoles 10 have high antitubercular activity with Minimum Inhibitory Concentration (MIC) of 0.7812-25.0 µg/mL (3.21-100.3 µM), against two strains of Mycobacterium tuberculosis sensitive to first-line drugs Isoniazid (INH), Rifampicin (RIF), Ethambutol (EMB), Pyrazinamide (PZE) (H37Rv) and a clinical isolate resistant to INH, RIF and EMB (G122). The cytotoxic evaluation shows that oxazoles have low activity, finding viability>96% against the VERO cell line. The results show these compounds could be considered as future alternatives for antitubercular treatment.