Bactericidal Permeability-Increasing Protein (BPI) Inhibits Mycobacterium tuberculosis Growth.

Bactericidal permeability-increasing protein (BPI) is a multifunctional cationic protein produced by neutrophils, eosinophils, fibroblasts, and macrophages with antibacterial anti-inflammatory properties. In the context of Gram-negative infection, BPI kills bacteria, neutralizes the endotoxic activity of lipopolysaccharides (LPSs), and, thus, avoids immune hyperactivation. Interestingly, BPI increases in patients with Gram-positive meningitis, interacts with lipopeptides and lipoteichoic acids of Gram-positive bacteria, and significantly enhances the immune response in peripheral blood mononuclear cells. We evaluated the antimycobacterial and immunoregulatory properties of BPI in human macrophages infected with Mycobacterium tuberculosis. Our results showed that recombinant BPI entered macrophages, significantly reduced the intracellular growth of M. tuberculosis, and inhibited the production of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-α). Furthermore, BPI decreased bacterial growth directly in vitro. These data suggest that BPI has direct and indirect bactericidal effects inhibiting bacterial growth and potentiating the immune response in human macrophages and support that this new protein's broad-spectrum antibacterial activity has the potential for fighting tuberculosis.

Selinexor, daratumumab, bortezomib and dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma: results of the phase II, non-randomized, multicenter GEM-SELIBORDARA study.

The treatment landscape for multiple myeloma has significantly evolved in the last decade. Notwithstanding, a large proportion of patients continue to relapse and novel combinations continue to be needed. In this phase 2 study, selinexor, a first-in-class inhibitor of exportin-1 was evaluated in combination with standard daratumumab-bortezomib-dexamethasone (DVd), for the treatment of relapsed and refractory multiple myeloma (RRMM). The aim of the trial was to assess the efficacy and safety of the combination of selinexor with DVd (S-DVd). A total of 57 patients were enrolled in the two parts of the study. Part 1 enrolled a heavily pretreated population with at least 3 prior lines of therapy and part 2 enrolled an early relapse population with at least 1 prior therapy. The primary endpoint was complete response (CR) rate in part 2 and overall response rate (ORR) in part 1. In the latter, 24 patients were treated with a median of 3 prior lines. Overall response rate (ORR) was 50% with 2 CR. Median progressionfree survival (PFS) was 7 months. In part 2, 33 patients were enrolled, with a median of 1 prior lines. ORR was 82% and CR or better was 33%. Median PFS was 24 months. In lenalidomide refractory patients, a median PFS of 22.1 months was observed. Thrombocytopenia was the most common hematological adverse event (69%; grade 3-4: 34%) and nausea, the most frequent nonhematological AE (38%; grade 3-4: 6%). 62% of the patients required dose modifications. In summary, although the primary endpoint of the study was not met, the combination of S-DVd showed encouraging clinical efficacy with a generally manageable safety profile representing a potential option for the treatment of RRMM patients.

Delay in the residents' choice for General and Digestive Surgery: Analysis of the period 2018-2022.

INTRODUCTION: Every year hundreds of medical residents choose their specialization in various surgical fields. However, these numbers have been poorly analyzed. The objective of this study was to evaluate the selection of General and Digestive Surgery by medical residents and compare these results with the selection of other surgical specialties. METHODS: Cross-sectional observational study. The data from the selection of the medical residents from surgical specialties and the top 10 most demanded specialties between the years 2018 and 2022 were included. An analysis of adjusted ranking numbers based on the number of available positions was also conducted. RESULTS: The number of available positions in General and Digestive Surgery increased by 17.7% during the study period. However, the selection of our specialty has been delayed, with a median ranking number of 2419 (IQR: 1621-3284) in 2018, and 3484 (IQR: 2306-4156) in 2022 (p: .000). These differences remained significant after adjusting for the number of available positions (p: .000). The choice of Urology, Thoracic Surgery, Cardiovascular Surgery, Gastroenterology, and Paediatrics also declined during this period, while Plastic Surgery, Dermatology, Ophthalmology, Anesthesiology, and Endocrinology improved their numbers. CONCLUSION: The choice of General and Digestive Surgery has been delayed according to the data from the MIR selection of 2018-2022. The increase in the number of available positions has not been associated with a proportional increase in demand.

Nanosuspensions as carriers of active ingredients: Chemical composition, development methods, and their biological activities.

Nanosuspensions (NSps) are colloidal dispersions of particles that have the potential to solve the delivery problems of active ingredients associated with their low solubility in water or instability due to environmental factors. It is essential to consider their chemical composition and preparation methods because they directly influence drug loading, size, morphology, solubility, and stability; these characteristics of nanosuspensions influence the delivery and bioavailability of active ingredients. NSps provides high loading of drugs, protection against degrading agents, rapid dissolution, high particle stability, and high bioavailability of active ingredients across biological membranes. In addition, they provide lower toxicity compared to other nanocarriers, such as liposomes or polymeric nanoparticles, and can modify the pharmacokinetic profiles, thus improving their safety and efficacy. The present review aims to address all aspects related to the composition of NSps, the different methods for their production, and the main factors affecting their stability. Moreover, recent studies are described as carriers of active ingredients and their biological activities.

Exploring COX-2 inhibitors in tuberculosis: A whole-blood model approach for immune response and adjunt therapy evaluation.

Pulmonary tuberculosis (TB) inflammation is an underestimated disease complication which anti-inflammatory drugs may alleviate. This study explored the potential use of the COX-2 inhibitors acetylsalicylic acid (ASA) and celecoxib in 12 TB patients and 12 healthy controls using a whole-blood ex vivo model where TNFα, PGE2, and LTB4 plasma levels were quantitated by ELISA; we also measured COX-2, 5-LOX, 12-LOX, and 15-LOX gene expression. We observed a significant TNFα production in response to stimulation with LPS or M. tuberculosis (Mtb). Celecoxib, but not ASA, reduced TNFα and PGE2 production, while increasing LTB4 in patients after infection with Mtb. Gene expression of COX-2 and 5-LOX was higher in controls, while 12-LOX was significantly higher in patients. 15-LOX expression was similar in both groups. We concluded that COX-2 inhibitors downregulate inflammation after Mtb infection, and our methodology offers a straightforward time-efficient approach for evaluating different drugs in this context. Further research is warranted to elucidate the underlying mechanisms and assess the potential clinical benefit.

Analysis of recurrence and risk factors in laparoscopic sandwich technique for parastomal hernia repair.

INTRODUCTION: Parastomal hernias are frequent and highly recurrent. The sandwich technique is a combination of the keyhole and Sugarbaker techniques, using a double intraperitoneal mesh. The objective of this study was to assess the outcomes of the sandwich technique, specifically focusing on recurrence rates. MATERIALS AND METHODS: Observational retrospective study conducted in two tertiary referral centers in Catalonia, Spain. All consecutive patients who underwent parastomal hernia repair using the sandwich technique between 1st January 2016 and 31st December 2021 were included. RESULTS: A total of 38 patients underwent the laparoscopic sandwich technique for parastomal hernia repair. The overall recurrence rate was 7.9% (3/38), with a median follow-up of 39 months (IQR: 12.3-56.5). According to the EHS classification for parastomal hernia, there were 47.4% (18/38) type I defects, 10.5% (4/38) type II defects, 28.9% (11/38) type III defects, and 13.2% (5/38) type IV defects. The used mesh was predominantly TiMesh® (76.3%; 29/38), followed by DynaMesh® IPOM (23.7%; 9/38). Patients with recurrence exhibited higher rates of seroma, hematoma, surgical site infection, and one case of early recurrence attributed to mesh retraction. Consequently, postoperative complications emerged as the primary risk factor for hernia recurrence. CONCLUSION: The sandwich technique demonstrated recurrence rates consistent with those reported in the existing literature.

Serum pro-inflammatory biomarkers associated with improvement in quality of life in pulmonary tuberculosis.

Introduction: Pulmonary dysfunction is an underestimated complication in tuberculosis (TB) infection, affecting quality of life (QoL). Although respiratory function tests objectively reflect lung disturbances in a specific moment, predictors of illness severity at the time of diagnosis are still lacking. Methods: We measured serum pro-inflammatory cytokines (TNF-α and IL-8), eicosanoids (PGE2, LTB4, RvD1, Mar1, and LXA4), a marker of tissue damage (cell-free nucleosomes), and indicators of redox status (malonaldehyde, 8-isoprostane, total oxidants, and antioxidants), as well as a score of radiological abnormalities (SRA) and a QoL questionnaire, in 25 patients with pulmonary TB at the time of diagnosis (t0) and two months after the initiation of treatment (t2). Results: We found higher antioxidant levels in the patients with the worst QoL at t0, and all the indicators of the prooxidant state were significantly reduced at t2, while the total antioxidant levels increased. LTB4, a pro-inflammatory eicosanoid, was diminished at t2, while all the pro-resolutory lipids decreased substantially. Significant correlations between the SRA and the QoL scores were observed, the latter showing a substantial reduction at t2, ranking it as a reliable tool for monitoring disease evolution during TB treatment. Discussion: These results suggest that evaluating a combination of these markers might be a valuable predictor of QoL improvement and a treatment response indicator; in particular, the oxidation metabolites and eicosanoid ratios could also be proposed as a future target for adjuvant therapies to reduce inflammation-associated lung injury in TB disease.

Real-World Health Care Services Utilization Associated With the Management of Patients With Relapsed and Refractory Multiple Myeloma in Spain: The CharisMMa Study.

BACKGROUND: Most patients with multiple myeloma (MM) relapse or become refractory, resulting in high health care costs. However, real-world data regarding the utilization of health care services among the relapsed/refractory MM (RRMM) population are scarce. METHODS: Observational, cross-sectional, multicenter study of the utilization of health care services by RRMM patients who had relapsed within the previous 6 months in Spain in a real-world setting. Data were collected from the clinical records and during a single structured interview and included sociodemographic and clinical characteristics at last relapse, the treatment and health care services nature, and were presented using descriptive statistics. RESULTS: The 276 patients enrolled (53.3% males), with a mean [SD] age of 67.4 [10.5] years, had experienced their most recent relapse a median (IQR) of 1.61 (0.74, 3.14) months before entering the study. Patients lived a median (IQR) of 9.0 (3.0, 30.0) km away from the hospital and visited the hospital a median (IQR) of 3.0 (2.0, 5.0) times/month to receive treatment for their most recent relapse. They spent a median (IQR) of 15.84 (5.0, 42.0) euros/month on transportation. Since their most recent relapse, most patients had been admitted to a hospital unit (n = 155, 56.2%), had required ≥1 diagnostic tests (n = 227, 82.2%), and had consulted the hematologist (n = 270, 97.8%) a mean (SD) of 5.5 (5.4) times. In half of the visits, patients were accompanied by an actively working caregiver (n = 112, 54.4%). CONCLUSIONS: RRMM treatments are associated with a high utilization of health care services and pose a significant burden for patients and caregivers. TRIAL REGISTRATION NUMBER: NCT03188536.

Parietex™ Composite Ventral Patch for primary and incisional hernia repair.

BACKGROUNDS: Ventral hernia repair with a preformed device is a frequent intervention, but few reports exist with Parietex™ Composite Ventral Patch. The aim was to evaluate the results of this mesh with the open intraperitoneal onlay mesh (open IPOM) technique. METHODS: Observational retrospective single institution study of all consecutive patients intervened for ventral or incisional hernia with a diameter inferior to 4 cm, from January 2013 to June 2020. The surgical repair was performed according to the open IPOM technique with Parietex™ Composite Ventral Patch. RESULTS: A total of 146 patients were intervened: 61.6% with umbilical hernias, 8.2% with epigastric hernias, 26.7% with trocar incisional hernias, and 3.4% with other incisional hernias. The global recurrence rate was 7.5% (11/146). Specifically, it was 7.8% in umbilical hernias, 0% in epigastric hernias, 7.7% in trocar incisional hernias and 20% (1/5) in other incisional hernias. The median time for recurrence was 14 months (IQR: 4.4-18.7). The median indirect follow-up was 36.9 months (IQR: 27.2-49.6), and the median presential follow-up was 17.4 months (IQR: 6.5-27.3). CONCLUSION: The open IPOM technique with a preformed patch offered satisfactory results for the treatment of ventral and incisional hernias.

Reduced IL-8 Secretion by NOD-like and Toll-like Receptors in Blood Cells from COVID-19 Patients.

Severe inflammatory responses are associated with the misbalance of innate and adaptive immunity. TLRs, NLRs, and cytokine receptors play an important role in pathogen sensing and intracellular control, which remains unclear in COVID-19. This study aimed to evaluate IL-8 production in blood cells from COVID-19 patients in a two-week follow-up evaluation. Blood samples were taken at admission (t1) and after 14 days of hospitalization (t2). The functionality of TLR2, TLR4, TLR7/8, TLR9, NOD1, and NOD2 innate receptors and IL-12 and IFN-γ cytokine receptors was evaluated by whole blood stimulation with specific synthetic receptor agonists through the quantification of IL-8, TNF-α, or IFN-γ. At admission, ligand-dependent IL-8 secretion was 6.4, 13, and 2.5 times lower for TLR2, TLR4, and endosomal TLR7/8 receptors, respectively, in patients than in healthy controls. Additionally, IL-12 receptor-induced IFN-γ secretion was lower in COVID-19 patients than in healthy subjects. We evaluated the same parameters after 14 days and observed significantly higher responses for TLR2, TLR4, TLR7/8, TLR9, and NOD1, NOD2, and IFN-γ receptors. In conclusion, the low secretion of IL-8 through stimulation with agonists of TLR2, TLR4, TLR7/8, TLR9, and NOD2 at t1 suggests their possible contribution to immunosuppression following hyperinflammation in COVID-19 disease.

Hospitalización a domicilio para pacientes quirúrgicos ante una pandemia por SARS-CoV-2: nuestra experiencia / Hospitalization at home for surgical patients in the face of a SARS-CoV-2 pandemic: our experience

Introducción: La hospitalización a domicilio para pacientes quirúrgicos (HaDQ) es una al-ternativa a la hospitalización convencional para pacientes quirúrgicos estables clínicamente, que precisen procedimientos de enfermería complejos por intensidad, frecuencia o carac-terísticas, y control por especialista quirúrgico en el domicilio.Método: Estudio transversal, descriptivo y retrospectivo de la actividad de la HADQ de nuestro hospital durante los primeros seis me-ses del 2020, para analizar la repercusión de la pandemia por SARS-CoV-2 en la unidad. Se distinguen tres periodos: prepandemia (enero-febreo), confinamiento (marzo-abril), poscon-finamiento (mayo-junio). Se diferencian dos grupos: A (HaD convencional) y B (despistaje preoperatorio COVID19). Se recogieron diver-sas variables: mes, tipo, estancia (HaD y hospi-tal), procedimientos, reingresos, domicilio, tipo visitas, COVID+. Se realizó un análisis estadís-tico descriptivo cuantitativo y cualitativo de los resultados obtenidosResultados: Ingresaron 345 pacientes, 225 en el grupo A (fase Pre (34%), fase C (40%), y fase Pos (25%)), y 120 en el B (fase C (75%), fase Pos (25%)). El confinamiento (fase C) fue el pe-ríodo más activo de la HADQ, tanto por número de ingresos (53%), como por la complejidad del grupo A que requería más procedimientos (71%) y más visitas domiciliarias (52%). Tam-bién aumentaron los pacientes de zona de no cobertura (42%), que implicaron visitas médicas y de enfermería en Hospital de Día (HD) (21%), y aumento de consultas telefónicas médicas (36%). En la fase Pos disminuyeron un 37% los ingresos del grupo A.Conclusiones: La HaDQ se reorganizó por la pandemia para atender a más pacientes quirúr-gicos, siendo un recurso asistencial esencial, especialmente durante el confinamiento. (AU)

Introduction: The HaDQ is an alternative to conventional hospitalization for clinically stable surgical patients who require complex nursing procedures due to intensity, frequency or char-acteristics, and control by a surgical specialist at home.Method: Cross-sectional, descriptive and ret-rospective study of the HADQ activity of our hospital during the first six months of 2020, to analyze the impact of the SARSCov2 pandemic in the unit. Three periods are distinguished: pre-pandemic (Jan-Feb), lockdown (Mar-Apr), post-lockdown (May-Jun). Two groups are differen-tiated: A (conventional HaD) and B (COVID19 preoperative screening). Various variables were collected: month, type, stay (HaD and hospi-tal), procedures, readmissions, address, type of visits, covid+. A quantitative and qualitative descriptive statistical analysis of the results ob-tained was carried out.Results: 345 patients were admitted, 225 in group A (phase Pre (34%), Phase C (40%), and phase Post (25%)), and 120 in group B (Phase C (75%), phase Post (25%)). %)). The confinement (phase C) was the most active period of the HADQ, both due to the number of admissions (53%), and the complexity of group A, which re-quired more procedures (71%) and more home visits (52%). There was also an increase in pa-tients from the non-coverage area (42%), which involved medical and nursing visits at the Day Hospital (HD) (21%), and an increase in medi-cal telephone consultations (36%). In the phase Post, the income of group A decreased by 37%.Conclusions: The HaDQ was reorganized due to the pandemic to care for more surgical pa-tients, being an essential care resource, espe-cially during confinement. (AU)

Diagnostic Performance and Clinical Applicability of Blood-Based Biomarkers in a Prospective Memory Clinic Cohort.

BACKGROUND AND OBJECTIVES: Blood-based biomarkers have emerged as minimally invasive options for evaluating cognitive impairment. Most studies to date have assessed them in research cohorts, limiting their generalization to everyday clinical practice. We evaluated their diagnostic performance and clinical applicability in a prospective, real-world, memory clinic cohort. METHODS: All patients referred with suspected cognitive impairment between July 2019 and June 2021 were prospectively invited to participate. Five plasma biomarkers (tau phosphorylated at threonine 181 [p-tau181], glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL], total tau [t-tau], and ubiquitin C-terminal hydrolase L1 [UCH-L1]) were determined with single-molecule array. Performance was assessed in comparison to clinical diagnosis (blinded to plasma results) and amyloid status (CSF/PET). A group of cognitively unimpaired (CU) controls was also included. RESULTS: Three hundred forty-nine participants (mean age 68, SD 8.3 years) and 36 CU controls (mean age 61.7, SD 8.2 years) were included. In the subcohort with available Alzheimer disease (AD) biomarkers (n = 268), plasma p-tau181 and GFAP had a high diagnostic accuracy to differentiate AD from non-neurodegenerative causes (area under the receiver operating characteristic curve 0.94 and 0.92, respectively), with p-tau181 systematically outperforming GFAP. Plasma p-tau181 levels predicted amyloid status (85% sensitivity and specificity) with accurate individual prediction in approximately 60% of the patients. Plasma NfL differentiated frontotemporal dementia (FTD) syndromes from CU (0.90) and non-neurodegenerative causes (0.93), whereas the discriminative capacity with AD and between all neurodegenerative and non-neurodegenerative causes was less accurate. A combination of p-tau181 and NfL identified FTD with 82% sensitivity and 85% specificity and had a negative predictive value for neurodegenerative diagnosis of 86%, ruling out half of the non-neurodegenerative diagnoses. In the subcohort without AD biomarkers, similar results were obtained. T-tau and UCH-L1 did not offer added diagnostic value. DISCUSSION: Plasma p-tau181 predicted amyloid status with high accuracy and could have potentially avoided CSF/amyloid PET testing in approximately 60% of subjects in a memory clinic setting. NfL was useful for identifying FTD from non-neurodegenerative causes but behaved worse than p-tau181 in all other comparisons. Combining p-tau181 and NfL improved diagnostic performance for FTD and non-neurodegenerative diagnoses. However, the 14% false-negative results suggest that further improvement is needed before implementation outside memory clinics. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that plasma p-tau181 correlates with the presence or absence of AD and a combination of plasma p-tau181 and NfL correlates moderately well with a diagnosis of FTD.

Mendelian Susceptibility to Mycobacterial Disease: Retrospective Clinical and Genetic Study in Mexico.

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by impaired immunity against intracellular pathogens, such as mycobacteria, attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains, and environmental mycobacteria in otherwise healthy individuals. Retrospective study reviewed the clinical, immunological, and genetic characteristics of patients with MSMD in Mexico. Overall, 22 patients diagnosed with MSMD from 2006 to 2021 were enrolled: 14 males (64%) and eight females. After BCG vaccination, 12 patients (70%) developed BCG infection. Furthermore, 6 (22%) patients developed bacterial infections mainly caused by Salmonella, as what is described next in the text is fungal infections, particularly Histoplasma. Seven patients died of disseminated BCG disease. Thirteen different pathogenic variants were identified in IL12RB1 (n = 13), IFNGR1 (n = 3), and IFNGR2 (n = 1) genes. Interleukin-12Rß1 deficiency is the leading cause of MSMD in our cohort. Morbidity and mortality were primarily due to BCG infection.

Mycobacterium tuberculosis whiB3 and Lipid Metabolism Genes Are Regulated by Host Induced Oxidative Stress

The physiological state of the human macrophage may impact the metabolism and the persistence of Mycobacterium tuberculosis. This pathogen senses and counters the levels of O2, CO, reactive oxygen species (ROS), and pH in macrophages. M. tuberculosis responds to oxidative stress through WhiB3. The goal was to determine the effect of NADPH oxidase (NOX) modulation and oxidative agents on the expression of whiB3 and genes involved in lipid metabolism (lip-Y, Icl-1, and tgs-1) in intracellular mycobacteria. Human macrophages were first treated with NOX modulators such as DPI (ROS inhibitor) and PMA (ROS activator), or with oxidative agents (H2O2 and generator system O2•-), and then infected with mycobacteria. We determined ROS production, cell viability, and expression of whiB3, as well as genes involved in lipid metabolism. PMA, H2O2, and O2•- increased ROS production in human macrophages, generating oxidative stress in bacteria and augmented the gene expression of whiB3, lip-Y, Icl-1, and tgs-1. Our results suggest that ROS production in macrophages induces oxidative stress in intracellular bacteria inducing whiB3 expression. This factor may activate the synthesis of reserve lipids produced to survive in the latency state, which allows its persistence for long periods within the host.

Human Pulmonary Tuberculosis: Understanding the Immune Response in the Bronchoalveolar System.

Mycobacterium tuberculosis, the causal agent of one of the most devastating infectious diseases worldwide, can evade or modulate the host immune response and remain dormant for many years. In this review, we focus on identifying the local immune response induced in vivo by M. tuberculosis in the lungs of patients with active tuberculosis by analyzing data from untouched cells from bronchoalveolar lavage fluid (BALF) or exhaled breath condensate (EBC) samples. The most abundant resident cells in patients with active tuberculosis are macrophages and lymphocytes, which facilitate the recruitment of neutrophils. The cellular response is characterized by an inflammatory state and oxidative stress produced mainly by macrophages and T lymphocytes. In the alveolar microenvironment, the levels of cytokines such as interleukins (IL), chemokines, and matrix metalloproteinases (MMP) are increased compared with healthy patients. The production of cytokines such as interferon (IFN)-γ and IL-17 and specific immunoglobulin (Ig) A and G against M. tuberculosis indicate that the adaptive immune response is induced despite the presence of a chronic infection. The role of epithelial cells, the processing and presentation of antigens by macrophages and dendritic cells, as well as the role of tissue-resident memory T cells (Trm) for in situ vaccination remains to be understood.

Opinions of nurses regarding Euthanasia and Medically Assisted Suicide.

BACKGROUND: Safeguarding the right to die according to the principles of autonomy and freedom of each person has become more important in the last decade, therefore increasing regulation of Euthanasia and Medically Assisted Suicide (MAS). AIMS: To learn the opinions that the nurses of the autonomous region of Madrid have regarding Euthanasia and Medically Assisted Suicide. RESEARCH DESIGN: Cross-sectional descriptive study. PARTICIPANTS AND RESEARCH CONTEXT: All registered nurses in Madrid. The study was done by means of a self-completed anonymous questionnaire. The variables studied were social-demographic, giving opinions about Euthanasia and MAS. ETHICAL CONSIDERATIONS: Each participant was assured maximum confidentiality and anonymity, ensuring the ethical principles set out in the Declaration of Helsinki, as well as in the Organic Law 3/2018, on Personal Data Protection and guarantee of digital rights. FINDINGS: A total of 489 nurses answered the questionnaire. In total, 75.7% of the nurses confirmed that Euthanasia should be regulated in Spain. 66.3% indicated that information on Euthanasia should be provided jointly by doctors and nurses, and 42.3% considered that it could be applied by both medical and nursing professionals. A total of 87.2% advocated the participation of nurses in health policy, influencing the drafting of the law. In the face of possible regulation, 35% would request Conscientious Objection, being closely related to their religious beliefs. DISCUSSION: Different authors point out that nurses' perceptions and attitudes towards Euthanasia are conditioned by different factors, such as religion, gender, poor palliative care, legality and the patient's right to die. CONCLUSION: Nurses are positioned in favour of the regulation and practice of Euthanasia and MAS, depending on their age, years of experience, training, model of care and especially religious beliefs.

Ultrasound-Assisted Extraction of Phenolic Compounds from Psidium cattleianum Leaves: Optimization Using the Response Surface Methodology.

In this study, conditions for the ultrasound-assisted extraction (UAE) of soluble polyphenols from Psidium cattleianum (PC) leaves were optimized using response surface methodology (RSM) by assessing the effect of extraction time (XET = 2, 4, and 6 min), sonication amplitude (XSA = 60, 80, and 100%), and pulse cycle (XPC = 0.4, 0.7, and 1 s). Furthermore, the optimized UAE conditions were compared with a conventional aqueous-organic extraction (AOE) method for extracting total phenolics; moreover, a phenolic profile using HPLC and antioxidant activity (DPPH, ABTS, and FRAP) were also compared. According to the RSM, the best conditions for UAE to extract the highest soluble polyphenol content and yield (158.18 mg/g dry matter [DM] and 15.81%) include a 100% sonication amplitude for 4 min at 0.6 s of pulse cycle. The optimal UAE conditions exhibited an effectiveness of 1.71 times in comparison to the AOE method for extracting total phenolics, in 96.66% less time; moreover, PC leaf extracts by UAE showed higher antioxidant values than AOE. Additionally, gallic, protocateic, chlorogenic, caffeic, coumaric, trans-cinnamic, 4-hydroxybenzoic, and syringic acids, as well as kaempferol were identified in PC leaves under UAE. PC leaf extracts are widely used for therapeutic and other industrial purposes; thus, the UAE proves to be a useful technology with which to improve the yield extraction of PC leaf phytochemicals.

Sex-Dependent Differential Expression of Lipidic Mediators Associated with Inflammation Resolution in Patients with Pulmonary Tuberculosis.

There is a sex bias in tuberculosis's severity, prevalence, and pathogenesis, and the rates are higher in men. Immunological and physiological factors are fundamental contributors to the development of the disease, and sex-related factors could play an essential role in making women more resistant to severe forms of the disease. In this study, we evaluated sex-dependent differences in inflammatory markers. Serum samples were collected from 34 patients diagnosed with pulmonary TB (19 male and 15 female) and 27 healthy controls (18 male and 9 female). Cytokines IL2, IL4, IL6, IL8, IL10, IFNγ, TNFα, and GM-CSF, and eicosanoids PGE2, LTB4, RvD1, and Mar1 were measured using commercially available immunoassays. The MDA, a product of lipidic peroxidation, was measured by detecting thiobarbituric-acid-reactive substances (TBARS). Differential inflammation patterns between men and women were observed. Men had higher levels of IL6, IL8, and TNFα than women. PGE2 and LTB4 levels were higher in patients than healthy controls, but there were no differences for RvD1 and Mar1. Women had higher RvD1/PGE2 and RvD1/LTB4 ratios among patients. RvD1 plays a vital role in resolving the inflammatory process of TB in women. Men are the major contributors to the typical pro-inflammatory profile observed in the serum of tuberculosis patients.

A simple score to predict early severe infections in patients with newly diagnosed multiple myeloma.

Infections remain a common complication in patients with multiple myeloma (MM) and are associated with morbidity and mortality. A risk score to predict the probability of early severe infection could help to identify the patients that would benefit from preventive measures. We undertook a post hoc analysis of infections in four clinical trials from the Spanish Myeloma Group, involving a total of 1347 patients (847 transplant candidates). Regarding the GEM2010 > 65 trial, antibiotic prophylaxis was mandatory, so we excluded it from the final analysis. The incidence of severe infection episodes within the first 6 months was 13.8%, and majority of the patients experiencing the first episode before 4 months (11.1%). 1.2% of patients died because of infections within the first 6 months (1% before 4 months). Variables associated with increased risk of severe infection in the first 4 months included serum albumin ≤30 g/L, ECOG > 1, male sex, and non-IgA type MM. A simple risk score with these variables facilitated the identification of three risk groups with different probabilities of severe infection within the first 4 months: low-risk (score 0-2) 8.2%; intermediate-risk (score 3) 19.2%; and high-risk (score 4) 28.3%. Patients with intermediate/high risk could be candidates for prophylactic antibiotic therapies.