Evaluation of naturally acquired immune responses against novel pre-erythrocytic Plasmodium vivax proteins in a low endemic malaria population located in the Peruvian Amazon Basin.

BACKGROUND: Plasmodium vivax represents the most geographically widespread human malaria parasite affecting civilian and military populations in endemic areas. Targeting the pre-erythrocytic (PE) stage of the parasite life cycle is especially appealing for developing P. vivax vaccines as it would prevent disease and transmission. Here, naturally acquired immunity to a panel of P. vivax PE antigens was explored, which may facilitate vaccine development and lead to a better understanding of naturally acquired PE immunity. METHODS: Twelve P. vivax PE antigens orthologous to a panel of P. falciparum antigens previously identified as highly immunogenic in protected subjects after immunization with radiation attenuated sporozoites (RAS) were used for evaluation of humoral and cellular immunity by ELISA and IFN-γ ELISpot. Samples from P. vivax infected individuals (n = 76) from a low endemic malaria region in the Peruvian Amazon Basin were used. RESULTS: In those clinical samples, all PE antigens evaluated showed positive IgG antibody reactivity with a variable prevalence of 58-99% in recently P. vivax diagnosed patients. The magnitude of the IgG antibody response against PE antigens was lower compared with blood stage antigens MSP1 and DBP-II, although antibody levels persisted better for PE antigens (average decrease of 6% for PE antigens and 43% for MSP1, p < 0.05). Higher IgG antibodies was associated with one or more previous malaria episodes only for blood stage antigens (p < 0.001). High IgG responders across PE and blood stage antigens showed significantly lower parasitaemia compared to low IgG responders (median 1,921 vs 4,663 par/µl, p < 0.05). In a subgroup of volunteers (n = 17),positive IFN-γ T cell response by ELISPOT was observed in 35% vs 9-35% against blood stage MSP1 and PE antigens, respectively, but no correlation with IgG responses. CONCLUSIONS: These results demonstrate clear humoral and T cell responses against P. vivax PE antigens in individuals naturally infected with P. vivax. These data identify novel attractive PE antigens suitable for use in the potential development and selection of new malaria vaccine candidates which can be used as a part of malaria prevention strategies in civilian and military populations living in P. vivax endemic areas.

Influence of diet and red wine exposure on the velocity of at home bleaching: A randomized controlled clinical trial.

PURPOSE: To evaluate the influence of diet and exposure to red wine on the treatment velocity, clinical results, postoperative tooth sensitivity, and patient satisfaction after tooth bleaching. METHODS: 45 subjects undergoing home bleaching with 16% carbamide peroxide (CP) were randomly separated into three groups, depending on the restriction of colored food and the use of a red wine mouthwash. Shades of teeth 11 and 21 were assessed using a digital spectrophotometer (VITA Easy Shade) at T0 (before treatment), T7 (7 days after treatment), T15 (15 days after treatment), and T30 (30 days after treatment). The assessments were verified using the CIELab system (values of L*, a*, and b*) and the change in shade was calculated (ΔE, ΔL, Δa, and Δb). RESULTS: No statistically significant differences in ΔE, ΔL, Δa, and Δb were found between the groups. However, at T7, the group restricted from colored foods without red wine mouthwash had meaningful variations in L*, a*, and b*. Statistically, there was no difference in tooth sensitivity between the groups in the 7- and 15-day periods. Patients in the restricted colored foods without red wine mouthwash group were more satisfied after the end of treatment. CLINICAL SIGNIFICANCE: Tooth bleaching with 16% carbamide peroxide may be performed in subjects with colorant-rich diets without influencing the clinical outcome.

Potentially inappropriate medications with risk of cardiovascular adverse events in the elderly: A systematic review of tools addressing inappropriate prescribing.

WHAT IS KNOWN AND OBJECTIVE: In the last decades, many lists have been developed to screen for inappropriate prescribing. However, information on which potentially inappropriate medications (PIMs) could increase the cardiovascular risk in the elderly is not objectively presented. This review aimed to identify and quantify those PIMs by extracting information from published PIM-lists. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA), a systematic review of PIM-lists was conducted. The search strategy was run in PubMed, MEDLINE and Google Scholar (1991-09/2017). All PIMs described in those lists were extracted and stratified by their potential cardiovascular risk (including major adverse cardiovascular events-MACE). The number of times each PIM was reported on those lists was also assessed. RESULTS AND DISCUSSION: We identified 724 papers, and 24 were retained. From those, a total of 17 PIMs to be avoided by the elderly and 21 drug-disease interactions were retrieved. The reporting of PIMs with risk of cardiovascular adverse events was 15.3%, whereas the reporting of those with MACE risk was 7.2%. PIMs most frequently described were tricyclic antidepressants (TCAs; 12/24), centrally acting antiadrenergic agents (11/24), NSAIDs (7/24), antiarrhythmics (Class I and III; 6/24), peripherally acting antiadrenergic agents (6/24) and antithrombotic agents (5/24). Most frequently described PIMs with MACE risk were NSAIDs (7/24), antiarrhythmics (Class I and III) (7/24), selective calcium channel blockers with vascular effects (6/24) and antipsychotics (4/24). WHAT IS NEW AND CONCLUSION: Data suggest that PIM-lists focus mainly on common adverse events and often poorly describe the potential consequence for MACE occurrence. This systematic review could help healthcare professionals in the identification and deprescribing of these medicines in older patients with high cardiovascular risk during medication review.

Can honey bees discriminate between floral-fragrance isomers?

Many flowering plants present variable complex fragrances, which usually include different isomers of the same molecule. As fragrance is an essential cue for flower recognition by pollinators, we ask whether honey bees discriminate between floral-fragrance isomers in an appetitive context. We used the olfactory conditioning of the proboscis extension response, which allows training a restrained bee to an odor paired with sucrose solution. Bees were trained under an absolute (a single odorant rewarded) or a differential conditioning regime (a rewarded versus a non-rewarded odorant) using four different pairs of isomers. One hour after training, discrimination and generalization between pairs of isomers were tested. Bees trained under absolute conditioning exhibited high generalization between isomers and discriminated only one out of four isomer pairs; after differential conditioning, they learned to differentiate between two out of four pairs of isomers but in all cases generalization responses to the non-rewarding isomer remained high. Adding an aversive taste to the non-rewarded isomer facilitated discrimination of isomers that otherwise seemed non-discriminable but generalization remained high. Although honey bees discriminated isomers under certain conditions, they achieved the task with difficulty and tended to generalize between them, thus showing that these molecules were perceptually similar to them. We conclude that the presence of isomers within floral fragrances might not necessarily contribute to a dramatic extent to floral odor diversity.

Mosquito bite immunization with radiation-attenuated Plasmodium falciparum sporozoites: safety, tolerability, protective efficacy and humoral immunogenicity.

BACKGROUND: In this phase 1 clinical trial, healthy adult, malaria-naïve subjects were immunized with radiation-attenuated Plasmodium falciparum sporozoites (PfRAS) by mosquito bite and then underwent controlled human malaria infection (CHMI). The PfRAS model for immunization against malaria had previously induced >90 % sterile protection against homologous CHMI. This study was to further explore the safety, tolerability and protective efficacy of the PfRAS model and to provide biological specimens to characterize protective immune responses and identify protective antigens in support of malaria vaccine development. METHODS: Fifty-seven subjects were screened, 41 enrolled and 30 received at least one immunization. The true-immunized subjects received PfRAS via mosquito bite and the mock-immunized subjects received mosquito bites from irradiated uninfected mosquitoes. Sera and peripheral blood mononuclear cells (PBMCs) were collected before and after PfRAS immunizations. RESULTS: Immunization with PfRAS was generally safe and well tolerated, and repeated immunization via mosquito bite did not appear to increase the risk or severity of AEs. Local adverse events (AEs) of true-immunized and mock-immunized groups consisted of erythaema, papules, swelling, and induration and were consistent with reactions from mosquito bites seen in nature. Two subjects, one true- and one mock-immunized, developed large local reactions that completely resolved, were likely a result of mosquito salivary antigens, and were withdrawn from further participation as a safety precaution. Systemic AEs were generally rare and mild, consisting of headache, myalgia, nausea, and low-grade fevers. Two true-immunized subjects experienced fever, malaise, myalgia, nausea, and rigours approximately 16 h after immunization. These symptoms likely resulted from pre-formed antibodies interacting with mosquito salivary antigens. Ten subjects immunized with PfRAS underwent CHMI and five subjects (50 %) were sterilely protected and there was a significant delay to parasitaemia in the other five subjects. All ten subjects developed humoral immune responses to whole sporozoites and to the circumsporozoite protein prior to CHMI, although the differences between protected and non-protected subjects were not statistically significant for this small sample size. CONCLUSIONS: The protective efficacy of this clinical trial (50 %) was notably less than previously reported (>90 %). This may be related to differences in host genetics or the inherent variability in mosquito biting behavior and numbers of sporozoites injected. Differences in trial procedures, such as the use of leukapheresis prior to CHMI and of a longer interval between the final immunization and CHMI in these subjects compared to earlier trials, may also have reduced protective efficacy. This trial has been retrospectively registered at ISRCTN ID 17372582, May 31, 2016.

Color-advertising strategies of invasive plants through the bee eye.

Invasive plants represent a significant global challenge as they compete with native plants for limited resources such as space, nutrients and pollinators. Here, we focused on four invasive species that are widely spread in the French Pyrenees, Buddleja davidii, Reynoutria japonica, Spiraea japonica and Impatiens glandulifera, and analyzed their visual advertisement signals with respect to those displayed by their surrounding native species using a perceptual approach based on the neural mechanisms of bee vision given that bees are regular pollinators of these plants. We collected 543 spectral reflections from the 4 invasive species, and 66 native species and estimated achromatic and chromatic similarities to the bee eye. R. japonica, S. japonica and B. davidii were inconspicuous against the foliage background and could be hardly discriminated in terms of color from their surrounding native plants. These characteristics promote generalization, potentially attracting pollinators foraging on similar native species. Two morphs of I. glandulifera were both highly salient in chromatic and achromatic terms and different from their surrounding native species. This distinctive identity facilitates detection and learning in association with rich nectar. While visual signals are not the only sensory cue accounting for invasive-plant success, our study reveals new elements for understanding biological invasion processes from the perspective of pollinator perceptual processes.

Assessment of Ammonia Emissions and Greenhouse Gases in Dairy Cattle Facilities: A Bibliometric Analysis.

A deeper understanding of gas emissions in milk production is crucial for promoting productive efficiency, sustainable resource use, and animal welfare. This paper aims to analyze ammonia and greenhouse gas emissions in dairy farming using bibliometric methods. A total of 187 English-language articles with experimental data from the Scopus and Web of Science databases (January 1987 to April 2024) were reviewed. Publications notably increased from 1997, with the highest number of papers published in 2022. Research mainly focuses on ammonia and methane emissions, including quantification, volatilization, and mitigation strategies. Other gases like carbon dioxide, nitrous oxide, and hydrogen sulfide were also studied. Key institutions include the University of California-Davis and Aarhus University. Bibliometric analysis revealed research evolution, identifying trends, gaps, and future research opportunities. This bibliometric analysis offers insights into emissions, air quality, sustainability, and animal welfare in dairy farming, highlighting areas for innovative mitigation strategies to enhance production sustainability. This research contributes to academia, enhancing agricultural practices, and informing environmental policies. It is possible to conclude that this research is a valuable tool for understanding the evolution of research on gas emissions in dairy cattle facilities, providing guidance for future studies and interventions to promote more sustainable production.

Neonicotinoid effects on tropical bees: Imidacloprid impairs innate appetitive responsiveness, learning and memory in the stingless bee Melipona quadrifasciata.

Together with other anthropogenic factors, pesticides play a major role in pollinator decline worldwide. Most studies on their influence on pollinators have focused on honey bees given the suitability of this insect for controlled behavioral testing and raising. Yet, studies on pesticide impact should also contemplate tropical species, which contribute a major part of biodiversity and which have remained so far neglected. Here we focused on the stingless bee Melipona quadrifasciata and asked if the widely used neonicotinoid imidacloprid disrupts its learning and memory capabilities. We fed stingless bees with 0.1, 0.5 or 1 ng of imidacloprid, tested their innate appetitive responsiveness and trained them to associate odors and sucrose reward using the olfactory conditioning of the proboscis extension response. The same experiments were performed on Africanized honey bees. One hour after intoxication, both species decreased their innate responsiveness to sucrose but the effect was more accentuated in stingless bees. In both species, learning and memory were affected in a dose-dependent manner. These results indicate that pesticides have dramatic consequences on tropical bee species and claim for rational policies regulating their use in the tropics.

Sex and lifestyle dictate learning performance in a neotropical wasp.

In contrast to extensive investigations on bee cognition, the cognitive capacities of wasps remain largely unexplored despite their key role as pollinators and predators of insect pests. Here we studied learning and memory in the neotropical wasp Mischocyttarus cerberus using a Pavlovian conditioning in which harnessed wasps respond with conditioned movements of their mouthparts to a learned odorant. We focused on the different castes, sexes, and ages coexisting within a nest and found that adults of M. cerberus learned and memorized efficiently the odor-sugar associations. In contrast, newly emerged females, but not males, were unable to learn odorants. This difference concurs with their different lifestyle as young males perform regular excursions outside the nest while young females remain in it until older age. Our results thus highlight the importance of socio-ecological constraints on wasp cognition and set the basis for mechanistic studies on learning differences across ages and castes.

Healthcare Professionals' Views on the Management of Medication Complexities in the Elderly With Mental Health Disorders: A Cross-Sectional Study.

Background: Many challenges in elderly pharmacotherapy are identified, including the use of Potentially Inappropriate Medications (PIMs) which may increase the odds of adverse events, especially in elderly patients with mental health disorders (e. g., behavioral, and psychological symptoms of dementia-BPSD, schizophrenia, bipolar disorder). However, information on the knowledge and practice of healthcare professionals (HCPs) about this topic is still scarce. Methods: A cross-sectional study was undertaken from July-October 2019. An online questionnaire was specifically designed and validated for this study. We sought HCPs (physicians, pharmacists, and nurses) worldwide, using (a) social media, via Facebook, Twitter, and LinkedIn; and (b) email contacts of the research team (convenience sample). Either way participants were asked to share on their social media or via e-mail the questionnaires with other HCPs (snowballing sample). The survey assessed two main domains: knowledge and practice. Knowledge was evaluated by self-report (perceived knowledge by a 5-item Likert confidence scale) and using three clinical cases, scored between 0 and 30 points (each one rated from 0 to 10 points; real knowledge). Barriers in clinical practice were evaluated using a 5-item Likert scale judging practitioners' opinion. Results: A total of 165 questionnaires were collected. HCPs were mainly female (n = 114; 69.1%), with a mean age of 35.3 ± 11.3 years old. Seventy-two percent (n = 118) were pharmacists, 21.1% (n = 35) were physicians, and 7.3% (n = 12) nurses. There was a weak correlation, albeit significant, between perceived and real knowledge (r = 0.199; p = 0.001). The mean score of the clinical vignettes regarding elderly patients with dementia and bipolar disorder were 4.59 ± 4.08 and 4.86 ± 2.97 points, respectively. Most HCPs were classified as having an intermediate knowledge (n = 100; 60.6%) about medication complexities in the elderly with mental disorders. Most HCPs agreed that lack of time (81.6%; n = 138), lack of education and training on elderly pharmacotherapy (72.2%; n = 122), and lack of tools adapted to daily practice (61.8%; n = 105) were the main barriers. Conclusions: Most of the HCPs felt confident to manage medication complexities in elder patients with mental disorders, but only a minority obtained a good score in the knowledge assessment test. The main barriers identified included structural barriers (tools unfit for practice) and process barriers (time).

Identification of two new protective pre-erythrocytic malaria vaccine antigen candidates.

BACKGROUND: Despite years of effort, a licensed malaria vaccine is not yet available. One of the obstacles facing the development of a malaria vaccine is the extensive heterogeneity of many of the current malaria vaccine antigens. To counteract this antigenic diversity, an effective malaria vaccine may need to elicit an immune response against multiple malaria antigens, thereby limiting the negative impact of variability in any one antigen. Since most of the malaria vaccine antigens that have been evaluated in people have not elicited a protective immune response, there is a need to identify additional protective antigens. In this study, the efficacy of three pre-erythrocytic stage malaria antigens was evaluated in a Plasmodium yoelii/mouse protection model. METHODS: Mice were immunized with plasmid DNA and vaccinia virus vectors that expressed one, two or all three P. yoelii vaccine antigens. The immunized mice were challenged with 300 P. yoelii sporozoites and evaluated for subsequent infection. RESULTS: Vaccines that expressed any one of the three antigens did not protect a high percentage of mice against a P. yoelii challenge. However, vaccines that expressed all three antigens protected a higher percentage of mice than a vaccine that expressed PyCSP, the most efficacious malaria vaccine antigen. Dissection of the multi-antigen vaccine indicated that protection was primarily associated with two of the three P. yoelii antigens. The protection elicited by a vaccine expressing these two antigens exceeded the sum of the protection elicited by the single antigen vaccines, suggesting a potential synergistic interaction. CONCLUSIONS: This work identifies two promising malaria vaccine antigen candidates and suggests that a multi-antigen vaccine may be more efficacious than a single antigen vaccine.

No association between periodontal disease and GHQ-12 in a Brazilian Police population.

OBJECTIVES: We attempt to investigate a possible association between periodontal disease (PD) and mental disorders (MD) in a population of Brazilian Police. STUDY METHOD: From a total study population consisting of 803 policemen, 345 police officers were obtained by a sample calculation using the finite population correction who were randomly selected in Montes Claros, Minas Gerais, Brazil. Patients who had been prescribed steroids or those diagnosed with diabetes and cardiovascular diseases were excluded from this study. The General Health Questionnaire (GHQ-12) was used to assess mental disorders. Odds ratios (ORs) for periodontal diseases severity and their respective 95% confidence intervals (CIs) were estimated. The risk of advanced scores in Clinical Attachment Level (CAL) and Community Periodontal Index (CPI) were estimated using Poisson Regression analyses. RESULTS: Only smoking and age were associated with severity in CAL and CPI index. No relation between MD and PD was observed even in different positions within the police department. CONCLUSIONS: It was not observed relation between GHQ-12 and the incidence of Periodontal Disease in a Brazilian Police population. Classical factors like age and smoking, however, were associated with CAL and CPI index higher scores in this population.

Awareness about barriers to medication adherence in cardiovascular patients and strategies used in clinical practice by Portuguese clinicians: a nationwide study.

BACKGROUND: Although much is known about cardiovascular patients' medication adherence, the extent to which clinicians perceive non-adherence as a barrier in clinical practice is little explored. Objective To evaluate knowledge and awareness about potential barriers to medication adherence, and to evaluate strategies used in clinical practice by Portuguese clinicians on how to foster medication adherence of patients undergoing secondary cardiovascular prevention. Setting Nominal Group Technique (NGT) at the University of Lisbon; online survey addressed to physicians working in primary and secondary care in Portugal. Method A narrative literature review was conducted in Pubmed to identify studies describing interventions targeted at physicians to manage medication adherence. The NGT included 12 allied healthcare professionals with recognized expertise in medication adherence and was organised in four phases, resulting in survey development. The survey was used in a cross-sectional national study where clinicians reported their knowledge and perceptions about patients' medication adherence and their daily practice. Main outcome measures Knowledge and awareness about barriers to medication adherence; and practice patterns. Results A total of 296 papers were identified, 26 of which were included. Four main topics were selected to be used in the NGT: adherence determinants, detecting non-adherence, fostering adherence, and educating physicians. NGT resulted in a survey, reaching 451 physicians, mostly practicing in primary care. Most had specific education on medication adherence and considered patient interviews and prescription records the most useful assessment methods. Nonetheless, many recognised often using clinical judgement to evaluate adherence in practice. Barriers to medication adherence were perceived to occur often during implementation. Most perceived reasons for uncontrolled hypertension were non-adherence to lifestyle recommendations and to medication. Less than half the physicians asked their patients if medication was taken. More useful enabling strategies included reducing daily doses, reviewing therapeutic options and motivational interventions. Conclusions Clinicians seem well informed about the importance of medication adherence and aware of problems encountered in practice. Limited time during medical appointment may be a barrier for better patient support.

What pollinators see does not match what they smell: Absence of color-fragrance association in the deceptive orchid Ionopsis utricularioides.

Many deceptive orchids present variation in floral color and fragrance. This might be advantageous for the plant, as it can disturb the associative avoidance learning of pollinators, promoting more visits to the flowers. Some studies have shown that color and fragrance can be correlated in polymorphic deceptive orchids, but these studies employed color traits based on the human visual system and not the visual perception of pollinators. Thus, we investigated the composition of the floral fragrance of Ionopsis utricularioides (Sw.) Lindl., a polymorphic deceptive orchid, and analyzed possible correlations with the floral color as seen by bees, Apis mellifera L. and Melipona quadrifasciata Lepeletier, using the color hexagon model. We found high color and fragrance intraspecific variation, as expected for deceptive species. However, we found no color-fragrance association in individuals, either by comparing fragrance profiles with the color variable saturation or by comparing them with the placement of individuals in the color hexagon for both bee species. This lack of correlation contradicts the biochemical pathway hypothesis, which proposes that associations between floral color and scent in polymorphic flowers arise from shared biochemical pathways. However, a complete absence of correlation between floral signals is consistent with selection arising through pollinator cognitive ecology. Lack of correlation would increase the floral variability perceived by bees, given their multimodal learning, and this variability could disrupt avoidance learning of deceptive flowers, thus enhancing the efficacy of the plant's deceptive pollination mechanism.

Histopathological Characterization of Mitral Valvular Lesions from Patients with Rheumatic Heart Disease. / Caracterização Histológica das Lesões da Valva Mitral de Pacientes com Cardiopatia Reumática.

BACKGROUND: The underlying mechanisms by which rheumatic heart disease (RHD) lead to severe valve dysfunction are not completely understood. OBJECTIVE: The present study evaluated the histopathological changes in mitral valves (MV) seeking an association between the pattern of predominant valvular dysfunction and histopathological findings. METHODS: In 40 patients who underwent MV replacement due to RHD, and in 20 controls that underwent heart transplant, histological aspects of the excised MV were analyzed. Clinical and echocardiographic data were also collected. Histological analyses were performed using hematoxylin-eosin staining. Inflammation, fibrosis, neoangiogenesis, calcification and adipose metaplasia were determined. A p value<0.05 was considered to be statistically significant. RESULTS: The mean age of RHD patients was 53±13 years, 36 (90%) were female, whereas the mean age of controls was 50±12 years, similar to the cases, with the majority of males (70%). The rheumatic valve endocardium presented greater thickness than the controls (1.3±0.5 mm versus 0.90±0.4 mm, p=0.003, respectively), and a more intense inflammatory infiltrate in the endocardium (78% versus 36%; p=0.004), with predominance of mononuclear cells. Moderate to marked fibrosis occurred more frequently in rheumatic valves than in control valves (100% vs. 29%; p<0.001). Calcification occurred in 35% of rheumatic valves, especially among stenotic valves, which was associated with the mitral valve area (p=0.003). CONCLUSIONS: Despite intense degree of fibrosis, the inflammatory process remains active in the rheumatic mitral valve, even at late disease with valve dysfunction. Calcification predominated in stenotic valves and in patients with right ventricular dysfunction.

FUNDAMENTOS: Os mecanismos subjacentes pelos quais a doença cardíaca reumática (DCR) levam à disfunção valvar grave não são totalmente compreendidos. OBJETIVO: O presente estudo avaliou as alterações histopatológicas nas valvas mitrais (VM) buscando uma associação entre o padrão de disfunção valvar predominante e os achados histopatológicos. MÉTODOS: Em 40 pacientes submetidos à troca da VM devido a DCR e em 20 controles submetidos a transplante cardíaco, foram analisados os aspectos histológicos da VM excisada. Dados clínicos e ecocardiográficos também foram coletados. As análises histológicas foram realizadas usando coloração com hematoxilina-eosina. Determinou-se inflamação, fibrose, neoangiogênese, calcificação e metaplasia adiposa. Valores de p<0,05 foram considerados estatisticamente significativos. RESULTADOS: A idade média dos pacientes com DCR foi de 53±13 anos, sendo 36 (90%) do sexo feminino, enquanto a idade média dos controles foi de 50±12 anos, semelhante aos casos, sendo a maioria do sexo masculino (70%). O endocárdio valvar reumático apresentou espessura maior que os controles (1,3±0,5 mm versus 0,90±0,4 mm, p=0,003, respectivamente), e infiltrado inflamatório mais intenso no endocárdio (78% versus 36%; p=0,004), com predominância de células mononucleares. Ocorreu fibrose moderada a acentuada mais frequentemente em válvulas reumáticas do que em válvulas controle (100% vs. 29%; p<0,001). Ocorreu calcificação em 35% das valvas reumáticas, principalmente entre as valvas estenóticas, associada à área valvar mitral (p=0,003). CONCLUSÕES: Apesar do intenso grau de fibrose, o processo inflamatório permanece ativo na valva mitral reumática, mesmo em doença tardia com disfunção valvar. A calcificação predominou em valvas estenóticas e em pacientes com disfunção ventricular direita.

A cognitive analysis of deceptive pollination: associative mechanisms underlying pollinators' choices in non-rewarding colour polymorphic scenarios.

Intraspecific floral colour polymorphism is a common trait of food deceptive orchids, which lure pollinators with variable, attractive signals, without providing food resources. The variable signals are thought to hinder avoidance learning of deceptive flowers by pollinators. Here, we analysed the cognitive mechanisms underlying the choice of free-flying stingless bees Scaptotrigona aff. depilis trained to visit a patch of artificial flowers that displayed the colours of Ionopsis utricularioides, a food deceptive orchid. Bees were trained in the presence of a non-rewarding colour and later tested with that colour vs. alternative colours. We simulated a discrete-polymorphism scenario with two distinct non-rewarding test colours, and a continuous-polymorphism scenario with three non-rewarding test colours aligned along a chromatic continuum. Bees learned to avoid the non-rewarding colour experienced during training. They thus preferred the novel non-rewarding colour in the discrete-polymorphic situation, and generalized their avoidance to the adjacent colour of the continuum in the continuous-polymorphism situation, favouring thereby the most distant colour. Bees also visited less flowers and abandoned faster a non-rewarding monomorphic patch than a non-rewarding polymorphic patch. Our cognitive analyses thus reveal that variable deceptive orchids disrupt avoidance learning by pollinators and exploit their generalization abilities, which make them favour distinct morphs.

Identification of a Set of Patient-Related Features to Foster Safe Prescribing of Specific Antipsychotics in the Elderly With Dementia.

Background: Antipsychotics (APs) are widely used to manage behavioral and psychiatric symptoms in dementia, although with a variety of adverse drug reactions. Therefore, it is important to know which patient-related features should be considered to foster a safe prescribing of these medications. Objectives: To compile and validate a set of patient-related features (PRFs) to foster safe prescribing of specific APs in the elderly with dementia; and to evaluate the feasibility of using them in clinical practice by analyzing the exhaustiveness of medical records. Method: A rapid literature review was the starting point, where PRFs were identified through a search in PubMed combined with information from the Summary of Product Characteristics (SmPCs). In the next step, a two-round e-Delphi survey was undertaken, where a total of 450 participants were invited by e-mail, including prescribers and specialists in benefit-risk assessment. Finally, a cross-sectional study was undertaken, where 100 patients were randomly extracted from the psychiatric hospital database. Outcomes were defined as the assessment of the clinical relevance and feasibility of the PRFs, and the level of exhaustiveness of these features in medical records. Data analysis was performed using univariate statistics (IBM SPSS v.23.0). Results: A total of 92 experts participated in the e-Delphi. Forty-seven PRFs obtained consensus, where 12 were applicable to haloperidol, 14 to olanzapine/risperidone, 13 to quetiapine, and 8 to aripiprazole. Age, comorbidities, and co-medications were rated as important features regardless of the prescribed drug. All PRFs were rated as always or frequently available and, if not, they were easy or partially easy to obtain. Age, comorbidities, and co-medications were always available in the medical records, whereas cognitive status (between 41.4 and 78.8%) or hepatic function (between 17.2 and 30.4%) presented a low-level of exhaustiveness. Conclusions: Even though a high number of PRFs were rated as clinically relevant, some of them were identified as frequently missing from medical records. This may suggest that medical records should be complemented with other sources (e.g., nursing and pharmacy records) to ensure a safe prescribing of APs.

The association between receptor binding affinity and metabolic side effect profile of antipsychotics and major cardio- and cerebrovascular events: A case/non-case study using VigiBase.

Antipsychotics (APs) have been associated with major adverse cardio- and cerebrovascular events (MACCE), but the underlying mechanisms are unclear. Our aim was to elucidate the association between APs, stratified for receptor affinity and metabolic side effects (MSE), in the reporting of MACCE. A case/non-case study was conducted using data from the WHO global Individual Case Safety Report (ICSR) database, VigiBase, among all reports associated with an AP. Cases were ICSRs of MACCE, while non-cases were all other adverse drug reactions (ADRs). APs were classified by AP group, the degree of receptor affinity for adrenergic, dopaminergic, muscarinic, histaminic, and serotoninergic receptors and by MSE profile. The strength of the association was estimated with logistic regression and expressed as crude and adjusted reporting odds ratios (RORadj.) with corresponding 95% confidence intervals (95%CIs). We identified 4987 reports of MACCE and 328,907 reports of other ADRs. Atypical APs (RORadj. 2.46; 95%CI 2.20-2.74) were significantly associated with the reporting of MACCE compared to typical ones. APs with high affinity for Adrenergic alfa-1 (RORadj. 2.98; 95%CI 1.93-4.59), Histaminic H1 (RORadj. 2.31; 95%CI 1.98-2.68), Muscarinic M1 (RORadj. 1.87; 95%CI 1.74-2.01), and Serotoninergic 5-HT2A (RORadj. 3.19; 95%CI 2.07-4.92) were associated with a higher risk of reporting of MACCE compared to low affinity. APs with higher-risk of MSE were associated with higher risk of reporting of MACCE (RORadj. 1.88; 95%CI 1.73-2.05) compared to the lower-risk. APs with high affinity for Adrenergic alfa-1, Histaminic H1, Muscarinic M1, and Serotoninergic 5-HT2A receptors and with high-risk of MSE may explain the occurrence of those events.

Intrafloral Color Modularity in a Bee-Pollinated Orchid.

Flower color has been studied in different ecological levels of organization, from individuals to communities. However, it is unclear how color is structured at the intrafloral level. In bee-pollinated flowers, the unidirectional gradient in color purity and pollen mimicry are two common processes to explain intrafloral color patterns. Considering that floral traits are often integrated, usually reflecting evolutionary modules under pollinator-mediated selection, we hypothesize that such intrafloral color patterns are structured by intrafloral color modules as perceived by bee color vision system. Here, we studied the tropical bee-pollinated orchid Cattleya walkeriana, given its intrafloral color complexity and variation among individuals. Considering bee color vision, we investigated if intrafloral color modules arose among intrafloral patches (tip or base of the sepals, petals, and labellum). We expected a separate color module between the labellum patches (the main attractive structure in orchids) and petals and sepals. We measured the color reflectance and calculated the photoreceptor excitation, spectral purity, hue, and the chromatic contrast of the floral structures in the hexagon color model. Spectral purity (saturation) was higher in the labellum tip in comparison to petals and sepals, generating a unidirectional gradient. Labellum base presented a less saturated yellow UV-absorbing color, which may reflect a pollen mimicry strategy. C. walkeriana presented three intrafloral color modules corresponding to the color of petals and sepals, the color of the labellum tip, and the color of labellum base. These color modules were unrelated to the development of floral structures. Given the importance of intrafloral color patterns in bee attraction and guidance, our results suggest that intrafloral patterns could be the outcome of evolutionary color modularization under pollinator-mediated selection.