Pharmaceutical targeting of the cannabinoid type 1 receptor impacts the crosstalk between immune cells and islets to reduce insulitis in humans.

AIMS/HYPOTHESIS: Insulitis, a hallmark of inflammation preceding autoimmune type 1 diabetes, leads to the eventual loss of functional beta cells. However, functional beta cells can persist even in the face of continuous insulitis. Despite advances in immunosuppressive treatments, maintaining functional beta cells to prevent insulitis progression and hyperglycaemia remains a challenge. The cannabinoid type 1 receptor (CB1R), present in immune cells and beta cells, regulates inflammation and beta cell function. Here, we pioneer an ex vivo model mirroring human insulitis to investigate the role of CB1R in this process. METHODS: CD4+ T lymphocytes were isolated from peripheral blood mononuclear cells (PBMCs) from male and female individuals at the onset of type 1 diabetes and from non-diabetic individuals, RNA was extracted and mRNA expression was analysed by real-time PCR. Single beta cell expression from donors with type 1 diabetes was obtained from data mining. Patient-derived human islets from male and female cadaveric donors were 3D-cultured in solubilised extracellular matrix gel in co-culture with the same donor PBMCs, and incubated with cytokines (IL-1ß, TNF-α, IFN-γ) for 24-48 h in the presence of vehicle or increasing concentrations of the CB1R blocker JD-5037. Expression of CNR1 (encoding for CB1R) was ablated using CRISPR/Cas9 technology. Viability, intracellular stress and signalling were assayed by live-cell probing and real-time PCR. The islet function measured as glucose-stimulated insulin secretion was determined in a perifusion system. Infiltration of immune cells into the islets was monitored by microscopy. Non-obese diabetic mice aged 7 weeks were treated for 1 week with JD-5037, then euthanised. Profiling of immune cells infiltrated in the islets was performed by flow cytometry. RESULTS: CNR1 expression was upregulated in circulating CD4+ T cells from individuals at type 1 diabetes onset (6.9-fold higher vs healthy individuals) and in sorted islet beta cells from donors with type 1 diabetes (3.6-fold higher vs healthy counterparts). The peripherally restricted CB1R inverse agonist JD-5037 arrested the initiation of insulitis in humans and mice. Mechanistically, CB1R blockade prevented islet NO production and ameliorated the ATF6 arm of the unfolded protein response. Consequently, cyto/chemokine expression decreased in human islets, leading to sustained islet cell viability and function. CONCLUSIONS/INTERPRETATION: These results suggest that CB1R could be an interesting target for type 1 diabetes while highlighting the regulatory mechanisms of insulitis. Moreover, these findings may apply to type 2 diabetes where islet inflammation is also a pathophysiological factor. DATA AVAILABILITY: Transcriptomic analysis of sorted human beta cells are from Gene Expression Omnibus database, accession no. GSE121863, available at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM3448161 .

Discrimination against the female surgeon in the exercise of her profession.

OBJECTIVE: To describe the discrimination experienced by the general female surgeon. METHOD: Prospective, cross-sectional and descriptive study, with a survey of 30 questions, closed, anonymous, voluntary and confidential, distributed through a link in the WhatsApp chat in a closed group of female surgeons who are members of the Asociación Mexicana de Cirugía General. RESULTS: 146 female surgeons participated, with a response rate of 58.4%. The discrimination perceived by female surgeons in training was 86 (58.9%), and 28 (19.2%) when they are already surgeons by not allowing them to perform the same procedures as their peers. Regarding the patients, discrimination against female surgeons was 72 (49.3%). They do not call them doctors, but "ladies", in 126 (86.3%), and they are asked to perform nursing duties in 120 (82.2%). On the other hand, there is also discrimination against female surgeons by nursing staff in 87 (59.6%). CONCLUSIONS: Discrimination is common in the daily surgical practice of female surgeons in all three areas: peers, patients, and nursing staff. This is an initial work, where the quantification of discrimination in Mexico is carried out. Strategies must be implemented to avoid discrimination against female surgeons and be in an environment of equality.

OBJETIVO: Describir la discriminación que vive la cirujana general en México. MÉTODO: Estudio prospectivo, transversal y descriptivo, con una encuesta de 30 preguntas cerradas, de manera anónima, voluntaria y confidencial, distribuida a través de un enlace en el chat de WhatsApp en un grupo cerrado de cirujanas de todo el país que son miembros de la Asociación Mexicana de Cirugía General. RESULTADOS: Participaron 146 cirujanas, con un porcentaje de respuesta del 58.4%. La discriminación percibida por las cirujanas en formación fue de 86 (58.9%), frente a 28 (19.2%) cuando ya son cirujanas, al no permitirles realizar los mismos procedimientos que sus pares. La discriminación por parte de los pacientes fue de 72 (49.3%). No las llaman doctoras sino «señoritas¼ en 126 (86.3%) y les solicitan hacer funciones de enfermería en 120 (82.2%). También existe discriminación hacia las cirujanas por el personal de enfermería en 87 (59.6%). CONCLUSIONES: La discriminación hacia las cirujanas es frecuente en los tres ámbitos: pares, pacientes y personal de enfermería. Este es un trabajo inicial, donde se realiza la cuantificación de la discriminación en México. Se deberán implementar las estrategias para evitar la discriminación a las cirujanas y estar en un ambiente de igualdad.

"I would prefer to be dead than to live this way": Lived experiences of stigma and discrimination against khwaja sira in Swat, Pakistan.

Due to their identification as third gender people, khwaja sira have historically been subjected to experiences of social marginalization. However, the extant literature has not fully explored the lived experiences of stigma and discrimination against khwaja sira in the Swat Valley of Khyber Pakhtunkhwa, Pakistan. To address this gap, we conducted 45 interviews with khwaja sira in Mingora, Swat, Khyber Pakhtunkhwa to better understand their experiences of gender-nonconformity stigma and discrimination in various social contexts, including within their families, in accessing health care, and within education and work contexts. Applying Minority Stress Theory and utilizing thematic content analysis, the present study identified three dimensions of gender-nonconformity stigma: (1) internalized stigma, namely feelings of shame and embarrassment; (2) perceived stigma, namely opinions others had of khwaja sira regarding lack of employability or engagement in sex work; and (3) enacted stigma, namely exclusion from families, in educational settings, in religious spaces, and in healthcare settings. Findings should inform future social intervention and community practice engagements with khwaja sira communities in Pakistan.

Analysis of Knowledge and Satisfaction in Virtual Clinical Simulation among Nursing Students: A Mixed Study.

Virtual simulation offers a powerful educational tool with considerable, albeit underexplored potential. This technology immerses students in lifelike digital scenarios, fostering the acquisition of knowledge and skills necessary for their future careers. This study aimed to assess knowledge acquisition and satisfaction outcomes among students using a virtual simulation teaching approach. The specific objectives were (1) to compare pre-and posttest knowledge acquisition, (2) to investigate the influence of prior professional experience on knowledge, and (3) to explore satisfaction levels with virtual simulation. One hundred and fifty-nine nursing students participated in a virtual simulation-based clinical intervention, entailing the resolution of a virtual adult patient hospitalized with respiratory pathology. Sociodemographic data and prior professional experience were collected, and knowledge was evaluated through pre-to-post tests. Satisfaction levels were assessed using open-ended questions. Quantitative data were analyzed using descriptive statistics, Wilcoxon, Mann-Whitney U, and Cohen's tests, while qualitative data underwent keyword-in-context analysis. Significant differences were noted between pre- and posttest knowledge levels, with prior experience showing no significant impact on knowledge acquisition. Participants reported high levels of satisfaction. Lexicometric analysis identified four clusters of words related to the key terms "simulation", "learn", "activity", and "knowledge". Virtual clinical simulation effectively enhances knowledge acquisition and fosters satisfaction, with students recognizing the positive impact of this approach on their learning. Consequently, virtual simulation contributes to the training of competent health professionals.

Reversible Capture Mechanism of CO2 as a Zn(II)-Methylcarbonate.

In this study, we elucidate the reaction mechanism for capturing CO2 with the ZnL1(MeOH) complex (L1 = diacetyl-2-(4-methyl-3-thiosemicarbazone)-3-(2-hydrazinatopyridine)) in a methanol solution, using density functional theory calculations. One pathway involves the protonation of ZnL1(MeOH) by methylcarbonic acid, followed by ligand exchange of MeOH with MeOCO2-. An alternative mechanism suggests a tautomerization between ZnL1(MeOH) and Zn(HL1)(OMe), followed by CO2 insertion. This latter pathway is energetically more favorable than the former and more complex than initially proposed. In fact, we unveiled that the solvent catalyzes tautomerization, as one explicit methanol molecule acts as a proton transfer agent. Then, Zn(HL1)(OMe) captures CO2, yielding a methylcarbonate bound to the metal center. The final step involves a rearrangement that leads to the cleavage of the Zn-O(Me)(COO) bond and the formation of a new Zn-O(COOMe) bond, along with the rotation of the methylcarbonate group. Furthermore, we evaluated the ligand basicity through the pKa calculated values of the Zn(II) complexes, the effects of varying the ligand from 4-methyl-thiosemicarbazone to 4-ethyl (L2), 4-phenethyl (L3), and 4-benzyl (L4) derivatives, and reversibility of the reaction in an argon environment.

Analysing disease trajectories in a cohort of 71,849 Patients: A visual analytics and statistical approach.

BACKGROUND: Disease trajectories have become increasingly relevant within the context of an aging population and the rising prevalence of chronic illnesses. Understanding the temporal progression of diseases is crucial for enhancing patient care, preventive measures, and effective management. OBJECTIVE: The objective of this study is to propose and validate a novel methodology for trajectory impact analysis and interactive visualization of disease trajectories over a cohort of 71,849 patients. METHODS: This article introduces an innovative comprehensive approach for analysis and interactive visualization of disease trajectories. First, Risk Increase (RI) index is defined that assesses the impact of the initial disease diagnosis on the development of subsequent illnesses. Secondly, visual graphics methods are used to represent cohort trajectories, ensuring a clear and semantically rich presentation that facilitates easy data interpretation. RESULTS: The proposed approach is demonstrated over the disease trajectories of a cohort comprising 71,849 patients from Tolosaldea, Spain. The study finds several clinically relevant trajectories in this cohort, such as that after suffering a cerebral ischemic stroke, the probability of suffering dementia increases 10.77 times. The clinical relevance of the study outcomes have been assessed by an in-depth analysis conducted by expert clinicians. The identified disease trajectories are in agreement with the latest advancements in the field. CONCLUSION: The proposed approach for trajectory impact analysis and interactive visualization offers valuable graphs for the comprehensive study of disease trajectories for improved clinical decision-making. The simplicity and interpretability of our methods make them valuable approach for healthcare professionals.

Comparison of the intrageneric neutralization scope of monospecific, bispecific/monogeneric and polyspecific/monogeneric antisera raised in horses immunized with sub-Saharan African snake venoms.

BACKGROUND: Snakebite envenomation inflicts a high burden of mortality and morbidity in sub-Saharan Africa. Antivenoms are the mainstay in the therapy of envenomation, and there is an urgent need to develop antivenoms of broad neutralizing efficacy for this region. The venoms used as immunogens to manufacture snake antivenoms are normally selected considering their medical importance and availability. Additionally, their ability to induce antibody responses with high neutralizing capability should be considered, an issue that involves the immunization scheme and the animal species being immunized. METHODOLOGY/PRINCIPAL FINDINGS: Using the lethality neutralization assay in mice, we compared the intrageneric neutralization scope of antisera generated by immunization of horses with monospecific, bispecific/monogeneric, and polyspecific/monogeneric immunogens formulated with venoms of Bitis spp., Echis spp., Dendroaspis spp., spitting Naja spp. or non-spitting Naja spp. It was found that the antisera raised by all the immunogens were able to neutralize the homologous venoms and, with a single exception, the heterologous congeneric venoms (considering spitting and non-spitting Naja separately). In general, the polyspecific antisera of Bitis spp, Echis spp, and Dendroaspis spp gave the best neutralization profile against venoms of these genera. For spitting Naja venoms, there were no significant differences in the neutralizing ability between monospecific, bispecific and polyspecific antisera. A similar result was obtained in the case of non-spitting Naja venoms, except that polyspecific antiserum was more effective against the venoms of N. melanoleuca and N. nivea as compared to the monospecific antiserum. CONCLUSIONS/SIGNIFICANCE: The use of polyspecific immunogens is the best alternative to produce monogeneric antivenoms with wide neutralizing coverage against venoms of sub-Saharan African snakes of the Bitis, Echis, Naja (non-spitting) and Dendroaspis genera. On the other hand, a monospecific immunogen composed of venom of Naja nigricollis is suitable to produce a monogeneric antivenom with wide neutralizing coverage against venoms of spitting Naja spp. These findings can be used in the design of antivenoms of wide neutralizing scope for sub-Saharan Africa.

Experiences of nursing students in A peer mentoring program during their clinical practices. A qualitative study.

BACKGROUND: Clinical placements allow nursing students to develop the skills and attitudes necessary to provide care. Peer mentoring programmes seem to facilitate these achievements, but there are very few studies on the effects of peer mentoring on clinical placements and what it can bring to both mentors and mentees. AIM: To describe the perspectives of nursing students on a peer mentoring programme during their clinical placements. DESIGN: A qualitative descriptive and exploratory study. SETTINGS AND PARTICIPANTS: First year and third year nursing students were included. METHODS: Focus groups were conducted with students after they participated in a peer mentoring programme during their clinical practice rotation. RESULTS: The support received from the student mentors was very important both academically and personally. Mentors also acknowledged having improved their teaching and leadership skills. CONCLUSIONS: Our results can be applied to future studies to inform peer mentoring programmes as a complementary teaching tool in clinical placements to improve leadership and empowerment in nursing students.

Transcriptomic Analysis of Extracellular Vesicles in the Search for Novel Plasma and Thrombus Biomarkers of Ischemic Stroke Etiologies.

Accurate etiologic diagnosis provides an appropriate secondary prevention and better prognosis in ischemic stroke (IS) patients; still, 45% of IS are cryptogenic, urging us to enhance diagnostic precision. We have studied the transcriptomic content of plasma extracellular vesicles (EVs) (n = 21) to identify potential biomarkers of IS etiologies. The proteins encoded by the selected genes were measured in the sera of IS patients (n = 114) and in hypertensive patients with (n = 78) and without atrial fibrillation (AF) (n = 20). IGFBP-2, the most promising candidate, was studied using immunohistochemistry in the IS thrombi (n = 23) and atrium of AF patients (n = 13). In vitro, the IGFBP-2 blockade was analyzed using thromboelastometry and endothelial cell cultures. We identified 745 differentially expressed genes among EVs of cardioembolic, atherothrombotic, and ESUS groups. From these, IGFBP-2 (cutoff > 247.6 ng/mL) emerged as a potential circulating biomarker of embolic IS [OR = 8.70 (1.84-41.13) p = 0.003], which was increased in patients with AF vs. controls (p < 0.001) and was augmented in cardioembolic vs. atherothrombotic thrombi (p < 0.01). Ex vivo, the blockage of IGFBP-2 reduced clot firmness (p < 0.01) and lysis time (p < 0.001) and in vitro, diminished endothelial permeability (p < 0.05) and transmigration (p = 0.06). IGFBP-2 could be a biomarker of embolic IS and a new therapeutic target involved in clot formation and endothelial dysfunction.

Clinical decision making: validation of the nursing anxiety and self-confidence with clinical decision making scale (NASC-CDM ©) into Spanish and comparative cross-sectional study in nursing students.

BACKGROUND: Decision making is a pivotal component of nursing education worldwide. This study aimed to accomplish objectives: (1) Cross-cultural adaptation and psychometric validation of the Nursing Anxiety and Self-Confidence with Clinical Decision Making (NASC-CDM©) scale from English to Spanish; (2) Comparison of nursing student groups by academic years; and (3) Analysis of the impact of work experience on decision making. METHODS: Cross-sectional comparative study. A convenience sample comprising 301 nursing students was included. Cultural adaptation and validation involved a rigorous process encompassing translation, back-translation, expert consultation, pilot testing, and psychometric evaluation of reliability and statistical validity. The NASC-CDM© scale consists of two subscales: self-confidence and anxiety, and 3 dimensions: D1 (Using resources to gather information and listening fully), D2 (Using information to see the big picture), and D3 (Knowing and acting). To assess variations in self-confidence and anxiety among students, the study employed the following tests: Analysis of Variance tests, homogeneity of variance, and Levene's correction with Tukey's post hoc analysis. RESULTS: Validation showed high internal consistency reliability for both scales: Cronbach's α = 0.920 and Guttman's λ2 = 0.923 (M = 111.32, SD = 17.07) for self-confidence, and α = 0.940 and λ2 = 0.942 (M = 80.44, SD = 21.67) for anxiety; and comparative fit index (CFI) of: 0.981 for self-confidence and 0.997 for anxiety. The results revealed a significant and gradual increase in students' self-confidence (p =.049) as they progressed through the courses, particularly in D2 and D3. Conversely, anxiety was high in the 1st year (M = 81.71, SD = 18.90) and increased in the 3rd year (M = 86.32, SD = 26.38), and significantly decreased only in D3. Work experience positively influenced self-confidence in D2 and D3 but had no effect on anxiety. CONCLUSION: The Spanish version (NASC-CDM-S©) was confirmed as a valid, sensitive, and reliable instrument, maintaining structural equivalence with the original English version. While the students' self-confidence increased throughout their training, their levels of anxiety varied. Nevertheless, these findings underscored shortcomings in assessing and identifying patient problems.

Methyl N-{(1R)-2-[(meth-oxy-carbon-yl)-oxy]-1-phenyleth-yl}carbamate.

The title mol-ecule, C12H15NO5, is a methyl carbamate derivative obtained by reacting (R)-2-phenyl-glycinol and methyl chloro-formate, with calcium hydroxide as heterogeneous catalyst. Supra-molecular chains are formed in the [100] direction, based on N-H⋯O hydrogen bonds between the amide and carboxyl-ate groups. These chains weakly inter-act in the crystal, and the phenyl rings do not display significant π-π inter-actions.

Association between patient activation and delayed discharge in elective laparoscopic cholecystectomy: A prospective cohort analysis.

BACKGROUND: Improving patient activation may be an effective way to reduce healthcare costs and improve patient outcomes after surgery. OBJECTIVE: To determine whether preoperative patient activation is associated with delayed discharge (i.e., length of stay >24 h) after elective laparoscopic cholecystectomy. Postoperative symptoms, unscheduled access to healthcare facilities within seven days of surgery, unplanned hospital readmissions, and postoperative complications were analyzed as secondary outcomes. DESIGN: This cohort study was a secondary analysis of the DeDiLaCo study (Delayed Discharge after day-surgery Laparoscopic Cholecystectomy) collecting data of patients undergoing elective laparoscopic cholecystectomy during 2021 in Italy. Data was analyzed from June 2022 to April 2023. SETTING: 90 Italian surgical centers participating in the study. PARTICIPANTS: 4708 adult patients with an instrumental diagnosis of gallbladder disease and undergoing laparoscopic cholecystectomy. Patient activation was assessed using the Italian translation of Patient Activation Measure in the preoperative setting. RESULTS: Of 4532 cases analyzed the median (IQR) Patient Activation Measure score was 80.3 (71.2-92.3). Participants were on average 55.5 years of age and 58.1 % were female. Two groups based on the activation level were created: 270 (6 %) had low activation, and 4262 had high activation. The low activation level was associated with the likelihood of delayed discharge (odds ratio [OR] 1.47, 95 % CI, 1.11-1.95; P = .008), higher symptom burden (OR 1.99, 95 % CI 1.49-2.66, P < .0001), and unplanned healthcare utilization within seven days after hospital discharge (OR 1.85, 95 % CI, 1.29-2.63; P = .001). There was no difference between the high and low activation groups in the incidence of postoperative complications (OR 1.28, 95 % CI, 0.95-1.73; P = .10) and hospital readmission after discharge (OR 0.95, 95 % CI, 0.30-3.05; P = .93). CONCLUSIONS: Our results suggest that patients with low activation have 1.47 times the risk of delayed discharge compared with patients with higher activation, almost twice the risk of the onset of postoperative symptoms, and 1.85 times the risk of unscheduled use of hospital services. Screening for patient activation in the preoperative setting could not only identify patients not suitable for early discharge, but more importantly, help physicians and nurses develop tailored interventions.

Brain atlas of the annual Garcialebias charrua fish.

Annual fish have become attractive study models for a wide range of disciplines, including neurobiology. These fish have developed different survival strategies. As a result, their nervous system is under considerable selective pressure when facing extreme environmental situations. Fish from the Austrolebias group exhibit rapid neurogenesis in different brain regions, possibly as a result of the demanding conditions of a changing habitat. Knowledge of cerebral histology is essential for detecting ontogenic, anatomical, or cytoarchitectonic changes in the brain during the short lifespan of these fish, such as those reflecting functional adaptive plasticity in different systems, including sensory structures. The generation of an atlas of Garcialebias charrua (previously known as Austrolebias charrua) establishes its anatomical basis as a representative of a large group of fish that share similarities in their way of life. In this work, we present a detailed study of both gross anatomy and microscopic anatomy obtained through serial sections stained with the Nissl technique in three orientations: transverse, horizontal, and parasagittal planes. This atlas includes accurate drawings of the entire adult brain of the male fish Garcialebias charrua, showing dorsal, ventral, and lateral views, including where emergence and origin of cranial nerves. This brain atlas allows us to understand histoarchitecture as well as the location of neural structures that change during adult neurogenesis, enabling comparisons within the genus. Simultaneously, this atlas constitutes a valuable tool for comparing the brains of other fish species with different behaviors and neuroecologies.

Applicability of an unsupervised cluster model developed on first wave COVID-19 patients in second/third wave critically ill patients.

OBJECTIVE: To validate the unsupervised cluster model (USCM) developed during the first pandemic wave in a cohort of critically ill patients from the second and third pandemic waves. DESIGN: Observational, retrospective, multicentre study. SETTING: Intensive Care Unit (ICU). PATIENTS: Adult patients admitted with COVID-19 and respiratory failure during the second and third pandemic waves. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Collected data included demographic and clinical characteristics, comorbidities, laboratory tests and ICU outcomes. To validate our original USCM, we assigned a phenotype to each patient of the validation cohort. The performance of the classification was determined by Silhouette coefficient (SC) and general linear modelling. In a post-hoc analysis we developed and validated a USCM specific to the validation set. The model's performance was measured using accuracy test and area under curve (AUC) ROC. RESULTS: A total of 2330 patients (mean age 63 [53-82] years, 1643 (70.5%) male, median APACHE II score (12 [9-16]) and SOFA score (4 [3-6]) were included. The ICU mortality was 27.2%. The USCM classified patients into 3 clinical phenotypes: A (n = 1206 patients, 51.8%); B (n = 618 patients, 26.5%), and C (n = 506 patients, 21.7%). The characteristics of patients within each phenotype were significantly different from the original population. The SC was -0.007 and the inclusion of phenotype classification in a regression model did not improve the model performance (0.79 and 0.78 ROC for original and validation model). The post-hoc model performed better than the validation model (SC -0.08). CONCLUSION: Models developed using machine learning techniques during the first pandemic wave cannot be applied with adequate performance to patients admitted in subsequent waves without prior validation.

The Celiac-Disease Superantigen Oligomerizes and Increases Permeability in an Enterocyte Cell Model.

Celiac disease (CeD) is an autoimmune disorder triggered by gluten proteins, affecting approximately 1 % of the global population. The 33-mer deamidated gliadin peptide (DGP) is a metabolically modified wheat-gluten superantigen for CeD. Here, we demonstrate that the 33-mer DGP spontaneously assembles into oligomers with a diameter of approximately 24 nm. The 33-mer DGP oligomers present two main secondary structural motifs-a major polyproline II helix and a minor ß-sheet structure. Importantly, in the presence of 33-mer DGP oligomers, there is a statistically significant increase in the permeability in the gut epithelial cell model Caco-2, accompanied by the redistribution of zonula occludens-1, a master tight junction protein. These findings provide novel molecular and supramolecular insights into the impact of 33-mer DGP in CeD and highlight the relevance of gliadin peptide oligomerization.

Cost-effectiveness and cost-utility study of a psychoeducational group intervention for people with depression and physical comorbidity in primary care.

OBJECTIVE: To evaluate the cost-effectiveness and cost-utility of a psychoeducational group intervention led by primary care (PC) nurses in relation to customary care to prevent the depression and improve quality of life in patients with physical comorbidity. DESIGN: Economic evaluation based on data from randomized, multicenter clinical trial with blind response variables and a one-year follow-up, carried in the context of the PSICODEP study. LOCATION: 7 PC teams from Catalonia. PARTICIPANTS: >50 year-old patients with depression and some physical comorbidity: diabetes mellitus type 2, ischemic heart disease, chronic obstructive pulmonary disease, and/or asthma. INTERVENTION: 12 psychoeducational group sessions, 1 per week, led by 2 PC nurses with prior training. MEASUREMENTS: Effectiveness: depression-free days (DFD) calculated from the BDI-II and quality-adjusted life years (QALYs) from the Euroqol-5D. Direct costs: PC visits, mental health, emergencies and hospitalizations, drugs. Indirect costs: days of temporary disability (TD). The incremental cost-effectiveness ratios (ICER), cost-effectiveness (ΔCost/ΔDLD) and cost-utility (ΔCost/ΔQALY) were estimated. RESULTS: The study includes 380 patients (intervention group [IG] = 204; control group [CG] = 176). 81.6% women; mean age 68.4 (SD = 8.8). The IG had a higher mean cost of visits, less of hospitalizations and less TD than the CG. The difference in costs between the IG and the CG was -357.95€ (95% CI: -2026.96 to 1311.06) at one year of follow-up. There was a mean of 11.95 (95% CI: -15.98 to 39.88) more DFD in the IG than in the CG. QALYs were similar (difference -0.01, 95% CI -0.04 to 0.05). The ICERs were 29.95€/DLD and 35,795€/QALY. CONCLUSIONS: Psychoeducational intervention is associated with an improvement in DFD, as well as a reduction in costs at 12 months, although not significantly. QALYs were very similar between groups.

Intrageneric cross-reactivity of monospecific rabbit antisera against venoms of mamba (Elapidae: Dendroaspis spp.) snakes.

Snakebite envenomation is a neglected tropical disease posing a high toll of mortality and morbidity in sub-Saharan Africa. Polyspecific antivenoms of broad effectiveness and specially designed for this region require a detailed understanding of the immunological features of the mamba snake (Dendroaspis spp.) venoms for the selection of the most appropriate antigen combination to produce antivenoms of wide neutralizing scope. Monospecific antisera were generated in rabbits against the venoms of the four species of mambas. The toxic effects of the immunization scheme in the animals were evaluated, antibody titers were estimated using immunochemical assays, and neutralization of lethal activity was assessed. By the end of the immunization schedule, rabbits showed normal values of the majority of hematological parameters tested. No muscle tissue damage was noticed, and no alterations in most serum chemical parameters were observed. Immunological analyses revealed a variable extent of cross-reactivity of the monospecific antisera against the heterologous venoms. The venoms of D. jamesoni and D. viridis generated the antisera with broader cross-reactivity by immunochemical parameters. The venoms of D. polylepis and D. viridis generated the antisera with better cross-neutralization of lethality, although the neutralizing ability of all antisera was lower than 0.16 mg venom/mL antiserum against either homologous or heterologous venoms. These experimental results must be scaled to large animal models used in antivenom manufacture at industrial level to assess whether these predictions are reproducible.