A Mixture of Four Probiotic Strains (Probiatop®) Mitigates Food Allergy to Ovalbumin in Mice.

Food allergy is a pathological condition caused by a disruption of oral tolerance. This condition leads to a pro-inflammatory environment that culminates in symptoms that varies from abdominal pain to anaphylaxis and death. The gold standard treatment consists of removing the food that triggers the allergy from diet. However, this conduct can cause nutritional impairment and social restrictions. Therefore, the need for new treatment strategies is notorious. In this context, probiotics are investigated due to their immunomodulatory mechanisms. Therefore, the objective of the present work is to investigate the probiotic potential of a mixture of four probiotic strains (Probiatop®) in an in vivo model of food allergy to ovalbumin (OVA). Our results demonstrated that oral administration of Probiatop® attenuated weight loss and diminished significantly anti-OVA IgE and IgG1 levels. Furthermore, it mitigated proximal jejunum injury, neutrophil recruitment and local IL17 levels. In addition, the probiotic mixture modulated positively the gut microbiota composition by decreasing the levels and frequency of Staphylococcus and yeast. In summary, our data suggest that Probiatop® has the potential to alleviate important symptoms of IgE-mediated food allergy, suggesting its probiotic potential as an adjuvant in the treatment of ovalbumin food allergy.

Can Vitamin D Levels Influence Bone Metabolism and Osseointegration of Dental Implants? An Umbrella Review.

INTRODUCTION: Due to the large amount of scientific evidence on the subject and the limitations and incongruities in previous reviews, the primary aim of this umbrella review is to gather all the information regarding the importance of vitamin D levels in the osseointegration of dental implants. METHODS: The literature search was performed in PubMed, Web of Science, CINAHL Plus, Cochrane Library, and Academic Search Complete throughout the search expression ["vitamin D" AND ("dental implant" OR "dental implants")]. RESULTS: The initial search yielded 351 results, but at the end of the process, only five systematic reviews were selected. CONCLUSIONS: Vitamin D seems to have a positive effect on the osseointegration of dental implants and on the reduction of dental implant failures; however, it is recommended that future studies take into account the limitations mentioned in this study in order to increase the validity and quality of scientific evidence on the subject.

Turning up the heat: Effects of temperature on agonistic acoustic communication in the two-spotted goby (Pomatoschistus flavescens).

Acoustic communication is linked to fitness traits in many animals, but under the current scenario of global warming, sound signals can be affected by rising temperatures, particularly in ectothermic organisms such as fishes. This study examines the effect of water temperature in acoustic communication in the two-spotted goby, Pomatoschistus flavescens. To address this, we looked at the effect of different temperatures on the acoustic features of drums produced by males during territorial defence and related it with their auditory sensitivity. We also analysed the differences in acoustic features between male agonistic drums and previously reported male courtship sounds, to better understand how acoustic communication may be affected by different temperature conditions. We recorded two-spotted goby males during territorial intrusions for 10 min at 16 °C, 19 °C, and 21 °C in the laboratory. We found that agonistic drums were shorter, had fewer pulses and shorter pulse periods at higher temperature, in contrast with the peak frequency that remained unaffected. Male agonistic and mating drums (recorded in a previous study) at 16 °C only differed in pulse period, which was higher in mating drums. Hearing thresholds obtained with Auditory Evoked Potentials at 16 °C, revealed higher sensitivity below 400 Hz, matching the main energy of agonistic and mating sounds. Our findings suggest that increasing temperature could potentially affect acoustic communication in this species by reducing the duration of agonistic drums, which might hinder effective communication. Nevertheless, the impact may not be significant as there was a good match between the best hearing sensitivity and the peak frequency range of their calls, which was not influenced by temperature. As fish and other organisms are increasingly threatened by multiple anthropogenic stressors, including warming, future research should address how changes in water temperature impact acoustic communication within a more realistic multi-stressor scenario.

Rapid progression of CD8 and CD4 T cells to cellular exhaustion and senescence during SARS-CoV2 infection.

Risk factors for the development of severe COVID-19 include several comorbidities, but age was the most striking one since elderly people were disproportionately affected by SARS-CoV-2 infection. Among the reasons for this markedly unfavorable response in the elderly, immunosenescence and inflammaging appear as major drivers of this outcome. A finding that was also notable was that hospitalized patients with severe COVID-19 have an accumulation of senescent T cells, suggesting that immunosenescence may be aggravated by SARS-CoV-2 infection. The present work was designed to examine whether these immunosenescence changes are characteristic of COVID-19 and whether it is dependent on disease severity using cross-sectional and longitudinal studies. Our cross-sectional data show that COVID-19, but not other respiratory infections, rapidly increased cellular senescence and exhaustion in CD4 and CD8 T cells during early infection. In addition, longitudinal analyses with patients from Brazil and Portugal provided evidence of increased frequencies of senescent and exhausted T cells over a 7-d period in patients with mild/moderate and severe COVID-19. Altogether, the study suggests that accelerated immunosenescence in CD4 and especially CD8 T-cell compartments may represent a common and unique outcome of SARS-CoV2 infection.

Development and Validation of a Game for Older Adults on Lifestyles and Frailty.

BACKGROUND: Games are a promising strategy for rehabilitating older adults. The effect of games on promoting healthy lifestyles and preventing frailty remains uncertain. This article aims to describe the process of development and validation of the game "Bem-me-quer para a saúde"® to promote the acquisition of healthy lifestyles and prevent frailty in over 65-year-olds. METHODS: This study comprised three distinct phases, spanning from December 2023 to June 2024. The first phase comprised a thorough review of the scientific literature on the frailty and lifestyles of older adults, a second phase of game design, and a third phase of content and semantic validation conducted by specialized nurses and older adults. RESULTS: After revising literature, this study utilized an e-Delphi with a panel of 14 specialist nurses who underwent two rounds of evaluation. The "Bem-me-quer para a saúde"® game includes a puzzle board with 54 pieces and 30 educational cards. In the final phase, we evaluated the game on a cohort of 50 older adults, highlighting its reflective, interactive, and educational aspects. CONCLUSIONS: The game presented sufficient evidence of content validity and relevance to clinical practice. We should conduct additional research to evaluate its impact on lifestyle modification and frailty prevention.

The metabolic and endocrine impact of diet-derived gut microbiota metabolites on ageing and longevity.

Gut dysbiosis has been recently recognized as a hallmark of ageing. At this stage of life, gut microbiota becomes depleted from bacteria involved in the production of short-chain fatty acids (SCFA), indole and its derivative indole-3-propionic acid (IPA), metabolites shown to improve host glycemic control as well as insulin sensitivity and secretion. Moreover, gut microbiota becomes enriched in pathobiont bacteria involved in the production of imidazole propionate, phenols and trimethylamine, metabolites that promote host insulin resistance and atherosclerosis. The magnitude of these changes is much more pronounced in unhealthy than in healthy ageing. On the other hand, a distinct gut microbiota signature is displayed during longevity, the most prominent being an enrichment in both SCFA and IPA bacterial producers. This short Review discusses, in an innovative and integrative way, cutting-edge research on the composition of gut microorganisms and profile of metabolites secreted by them, that are associated with a healthy and unhealthy ageing pattern and with longevity. A detailed description of the positive or detrimental metabolic effects, in the ageing host, of diet-derived gut microbial metabolites is provided. Finally, microbiota-targeted interventions that counteract gut dysbiosis associated with ageing, are briefly outlined.

Obesity alters the macrophages' response to Leishmania major in C57BL/6 mice.

Obesity is a global pandemic associated with several comorbidities, such as cardiovascular diseases and type 2 diabetes. It is also a predisposing factor for infectious diseases, increasing mortality rates. Moreover, diet-induced obesity can cause metabolic fluctuations that affect macrophage differentiation in various organs. In this sense, we investigated how bone marrow-derived macrophages and tissue-resident macrophages in the skin, which have been differentiated in a host with metabolic syndrome and with previous inflammatory burden, respond to Leishmania major infection. Our findings suggest that bone marrow-derived macrophages from obese C57BL/6 mice, even when cultivated in vitro with inflammatory stimuli, are more susceptible to L. major. These macrophages produce less tumor necrosing factor (TNF) and nitric oxide (NO) and show higher arginase activity. Furthermore, obese mice infected with an intermediate dose of L. major in the skin had more severe lesions when analyzed for ulceration, diameter, thickness, and parasite burden. The increase in lesion severity in obese mice was associated with a higher frequency of tissue-resident macrophages, which are less efficient in killing parasites. We also used CCR2-/- mice, which predominantly have tissue-resident macrophages, and found that lesion resolution was delayed in association with CCR2 deficiency. Additionally, obesity potentiated tissue damage, resulting in higher frequency of tissue-resident macrophages. Our results demonstrate that obesity can alter macrophage responses to infection, leading to increased susceptibility to L. major and more severe cutaneous leishmaniasis. These findings may have important implications for managing obesity-related infections and the development of new therapies for cutaneous leishmaniasis.

Sand smelt larvae's resilience to hypoxia and implications for thermal tolerance.

Deoxygenation is a growing threat to marine ecosystems, with an increase in the frequency, extent and intensity of hypoxia events in recent decades. These phenomena will pose various challenges to marine species, as it affects their survival, growth, body condition, metabolism and ability to handle other environmental stressors, such as temperature. Early life stages are particularly vulnerable to these changes. Thus, it is crucial to understand how these initial phases will respond to hypoxia to predict the impacts on marine populations and ecosystems. In this work, we aimed to evaluate the effect of oxygen (O2) availability on fitness related traits (mortality, growth and body condition), metabolism (Routine metabolic rates [RMR]) and thermal tolerance (CTmax), in early stages of Atherina presbyter, exposed for two weeks, to two O2 levels: normoxia (6.5-7.2 mg L-1) and hypoxia (2-2.5 mg L-1), through an experiment setup. Our findings showed that while low oxygen levels did not negatively impact mortality, total length, weight, or body condition (Fulton K), the larvae undergo metabolic depression when exposed to hypoxia, as an energy conservation mechanism. Furthermore, CTmax suffered a significant reduction in low O2 availability, due to the inability of the circulatory and respiratory systems to fulfill energy demands. These outcomes suggest that although early life stages of Atherina presbyter can survive under low oxygen environments, they are less capable of dealing with sudden increases in temperature when oxygen is scarce.

Cutaneous Application of Capsaicin Cream Reduces Clinical Signs of Experimental Colitis and Repairs Intestinal Barrier Integrity by Modulating the Gut Microbiota and Tight Junction Proteins.

Capsaicin, a pungent compound in chili peppers, is described as having potent anti-inflammatory, antioxidant, and antimicrobial properties. It is also described as a potential modulator of the immune system and intestinal microbiota. Oral or rectal administration of capsaicin has been studied to treat or prevent colitis. However, those vias are often not well accepted due to the burning sensation that capsaicin can cause. Our objective was to evaluate whether the application of capsaicin skin creams (0.075%) would be effective in improving inflammation and epithelial barrier function as well as the composition of the gut microbiota in a model of mild colitis induced by dextran sulfate sodium (1.5%). The results showed that the cutaneous application of capsaicin reversed weight loss and decreased colon shortening and diarrhea, all typical signs of colitis. There was also an improvement in the intestinal epithelial barrier, preserving proteins from tight junctions. We also evaluated the biodistribution of 99mtechnetium-radiolabeled capsaicin (99mTc-CAPS) applied to the back skin of the animals. We found significant concentrations of 99 mTc-Cap in the colon and small intestine after 2 and 4 h of administration. In addition, there was an increased expression of capsaicin receptor TRPV1 in the colon. Moreover, animals with colitis receiving cutaneous capsaicin presented a better short-chain fatty acid profile and increased levels of SIgA, suggesting increased microbiota diversity. In conclusion, our work opens avenues for further studies to better understand capsaicin's potential benefits and mechanisms in addressing colitis through cutaneous application.

Nurses' perspectives on nurses' work methods.

OBJECTIVES: To analyze nurses' perspectives on nurses' work methods in the hospital context. METHODS: A descriptive study with a qualitative approach was conducted in a hospital in northern Portugal, involving 17 nurses. Semi-structured interviews were used for data collection. Data collected between May and June 2023 underwent content analysis, supported by Atlas.ti software. RESULTS: Three thematic areas emerged: "Nurses' work methods in a hospital context," highlighting the conception and components of work methods and the methods in use; "Implementation of nurses' work methods," emphasizing influencing factors and challenges to implementation; and "Impact of nurses' work methods on patients, nurses, and institutions." FINAL CONSIDERATIONS: Nurses' work methods constitute the structure of nursing care. Some factors influence and some challenges arise in the implementation of these methods, producing impacts on patients, nurses, and institutions.

Biochemical and Anthropometric Outcomes in Paediatric Patients with Heterozygous Familial Hypercholesterolemia after COVID-19 Pandemic Lockdowns: An Exploratory Analysis.

The COVID-19 pandemic lockdowns affected the lifestyles of children and adolescents, leading to an increase in childhood obesity. Paediatric patients with familial hypercholesterolemia (FH) may be more susceptible to lockdown effects due to their increased cardiovascular risk. However, data are lacking. We investigated the effect of lockdowns on the metabolic profile of paediatric patients with FH. Blood lipids and anthropometry measured in September 2021-April 2022 were retrospectively compared with pre-pandemic values. Thirty participants were included (1-16 years; 57% female). From baseline to post-pandemic, median [P25, P75] blood LDL-C concentration was 125 [112, 150] mg/dL vs. 125 [100, 147] mg/dL (p = 0.894); HDL-C was 58 [52, 65] mg/dL vs. 56 [51, 61] mg/dL (p = 0.107); triglycerides were 64 [44, 86] mg/dL vs. 59 [42, 86] mg/dL (p = 0.178). The BMI z-score did not change significantly (0.19 [-0.58, 0.89] vs. 0.30 [-0.48, 1.10], p = 0.524). The lack of deterioration in metabolic profiles during lockdowns is positive, as some deterioration was expected. We speculate that patients and caregivers were successfully educated about healthy lifestyle and dietary habits. Our results should be interpreted with caution since the study sample was small and heterogeneous. Multicentre research is needed to better understand the impact of lockdowns on this population.

Scale for the environments evaluation of professional nursing practice-shortened version: Psychometric evaluation.

AIM: The aim of this study is to test the validity and reliability of the shortened version of the Scale for the Environments Evaluation of Professional Nursing Practice (SEE-Nursing Practice). METHODS: This methodological, cross-sectional study was conducted between September and December 2022. The original version of the SEE-Nursing Practice was administered in questionnaire format across 17 hospitals. Exploratory and confirmatory factor analyses were conducted to identify relevant items for the new shortened version of the scale and evaluate its construct validity. RESULTS: The study involved 1713 registered nurses from various regions of Portugal. From the exploratory factor analysis, the SEE-Nursing Practice was condensed to 59 items and 3 subscales. In the structure subscale, 14 items were removed, and the remaining 29 items distributed over four factors; in the process subscale, 18 items were removed, and the remaining 19 items organized into three factors; in the outcome subscale, 2 items were removed, and the remaining 11 items distributed over two factors. The Cronbach's alpha for the three subscales exceeded 0.90, indicating high reliability. Confirmatory factor analyses provided support for the validity of the 59-item model. CONCLUSION: The shortened version of the SEE-Nursing Practice shows adequate validity and reliability, reducing the burden associated with its longer version.

Dietary protein modulates intestinal dendritic cells to establish mucosal homeostasis.

Dietary proteins are taken up by intestinal dendritic cells (DCs), cleaved into peptides, loaded to major histocompatibility complexes, and presented to T cells to generate an immune response. Amino acid (AA)-diets do not have the same effects because AAs cannot bind to major histocompatibility complex to activate T cells. Here, we show that impairment in regulatory T cell generation and loss of tolerance in mice fed a diet lacking whole protein is associated with major transcriptional changes in intestinal DCs including downregulation of genes related to DC maturation, activation and decreased gene expression of immune checkpoint molecules. Moreover, the AA-diet had a profound effect on microbiome composition, including an increase in Akkermansia muciniphilia and Oscillibacter and a decrease in Lactococcus lactis and Bifidobacterium. Although microbiome transfer experiments showed that AA-driven microbiome modulates intestinal DC gene expression, most of the unique transcriptional change in DC was linked to the absence of whole protein in the diet. Our findings highlight the importance of dietary proteins for intestinal DC function and mucosal tolerance.

Physical Activity during Pregnancy and Risk of Gestational Diabetes Mellitus: A Meta-Review.

BACKGROUND: Nowadays, pregnant women require more individualized attention in their assistance process during pregnancy. One of the aspects that requires the most focus is the suitability of carrying out physical activity. The objective of this meta-review is to find out the effects of physical activity during pregnancy on the incidence of GDM compared to women who do not perform physical activity. METHODS: A search was conducted in Cochrane, CSIC, Ebscohost, Proquest, Pubmed, Scielo, and Scopus. The search focused on systematic reviews and meta-analyses published in the last five years. The AMSTAR-2 scale was used as a quality assessment tool for the final sample. RESULTS: A total of 18 systematic reviews and meta-analyses were included. Sixteen of them found out that physical activity during pregnancy has preventive effects for GDM compared with women who lacked physical activity. Among the studies, we found a reduction in the risk of GDM of between 24% and 38% and odds ratios ranging between 0.39 and 0.83 calculated for a 95% CI. Only two studies did not find statistically significant effects. Other variables such as type and duration of physical activity, overweight and obesity, gestational age, etc., were also considered. CONCLUSIONS: Physical activity prevents the incidence of GDM. The main characteristics that enhance this preventive effect are starting at the initial stages of pregnancy and maintaining during the whole pregnancy as well as combining strength and aerobic exercise at a low to moderate intensity.

Integrated behavioural and physiological responses of sand smelt larvae to the effects of warming and hypoxia as combined stressors.

Forecasts indicate that rising temperatures towards the future and the expansion of dead zones will change environmental suitability for fish early stages. Therefore, we assessed the chronic effects of warming (26 °C), hypoxia (<2-2.5 mg L-1) or their combination on mortality rate, growth, behaviour, energy metabolism and oxidative stress using Atherina presbyter larvae as a model species. There were no differences between the treatments in terms of mortality rate. The combination of warming and hypoxia induced faster loss of body mass (+22.7%). Warming, hypoxia or their combination enhanced boldness (+14.7-25.4%), but decreased exploration (-95%-121%), increased the time in frozen state (+60.6-80.5%) and depleted swimming speed (-45.6-50.5%). Moreover, routine metabolic rate was depleted under hypoxia or under the combination of warming and hypoxia (-56.6 and 57.2%, respectively). Under hypoxia, increased catalase activity (+56.3%) indicates some level of antioxidant defence capacity, although increased DNA damage (+25.2%) has also been observed. Larvae also exhibited a great capacity to maintain the anaerobic metabolism stable in all situations, but the aerobic metabolism is enhanced (+19.3%) when exposed to the combination of both stressors. The integrative approach showed that changes in most target responses can be explained physiologically by oxidative stress responses. Increased oxidative damages (lipid peroxidation and DNA damage) and increased interaction between antioxidant enzymes (superoxide dismutase and catalase) are associated to increased time in frozen state and decreased swimming activity, growth rates and boldness. Under all stressful situations, larvae reduced energy-consuming behaviours (e.g. depleted exploration and swimming activity) likely to stabilize or compensate for the aerobic and anaerobic metabolisms. Despite being an active small pelagic fish, we concluded that the sensitive larval phase exhibited complex coping strategies to physiologically acclimate under thermal and hypoxic stress via behavioural responses.

Lactobacillus delbrueckii CIDCA 133 fermented milk modulates inflammation and gut microbiota to alleviate acute colitis.

Lactobacillus delbrueckii subsp. lactis CIDCA 133 is a health-promoting bacterium that can alleviate gut inflammation and improve the epithelial barrier in a mouse model of mucositis. Despite these beneficial effects, the protective potential of this strain in other inflammation models, such as inflammatory bowel disease, remains unexplored. Herein, we examined for the first time the efficacy of Lactobacillus delbrueckii CIDCA 133 incorporated into a fermented milk formulation in the recovery of inflammation, epithelial damage, and restoration of gut microbiota in mice with dextran sulfate sodium-induced colitis. Oral administration of Lactobacillus delbrueckii CIDCA 133 fermented milk relieved colitis by decreasing levels of inflammatory factors (myeloperoxidase, N-acetyl-ß-D-glucosaminidase, toll-like receptor 2, nuclear factor-κB, interleukins 10 and 6, and tumor necrosis factor), secretory immunoglobulin A levels, and intestinal paracellular permeability. This immunobiotic also modulated the expression of tight junction proteins (zonulin and occludin) and the activation of short-chain fatty acids-related receptors (G-protein coupled receptors 43 and 109A). Colonic protection was effectively associated with acetate production and restoration of gut microbiota composition. Treatment with Lactobacillus delbrueckii CIDCA 133 fermented milk increased the abundance of Firmicutes members (Lactobacillus genus) while decreasing the abundance of Proteobacteria (Helicobacter genus) and Bacteroidetes members (Bacteroides genus). These promising outcomes influenced the mice's mucosal healing, colon length, body weight, and disease activity index, demonstrating that this immunobiotic could be explored as an alternative approach for managing inflammatory bowel disease.

Systematic challenges and opportunities in insect monitoring: a Global South perspective.

Insect monitoring is pivotal for assessing biodiversity and informing conservation strategies. This study delves into the complex realm of insect monitoring in the Global South-world developing and least-developed countries as identified by the United Nations Conference on Trade and Development-highlighting challenges and proposing strategic solutions. An analysis of publications from 1990 to 2024 reveals an imbalance in research contributions between the Global North and South, highlighting disparities in entomological research and the scarcity of taxonomic expertise in the Global South. We discuss the socio-economic factors that exacerbate the issues, including funding disparities, challenges in collaboration, infrastructure deficits, information technology obstacles and the impact of local currency devaluation. In addition, we emphasize the crucial role of environmental factors in shaping insect diversity, particularly in tropical regions facing multiple challenges including climate change, urbanization, pollution and various anthropogenic activities. We also stress the need for entomologists to advocate for ecosystem services provided by insects in addressing environmental issues. To enhance monitoring capacity, we propose strategies such as community engagement, outreach programmes and cultural activities to instill biodiversity appreciation. Further, language inclusivity and social media use are emphasized for effective communication. More collaborations with Global North counterparts, particularly in areas of molecular biology and remote sensing, are suggested for technological advancements. In conclusion, advocating for these strategies-global collaborations, a diverse entomological community and the integration of transverse disciplines-aims to address challenges and foster inclusive, sustainable insect monitoring in the Global South, contributing significantly to biodiversity conservation and overall ecosystem health. This article is part of the theme issue 'Towards a toolkit for global insect biodiversity monitoring'.

Dynamic changes in B cell subpopulations in response to triple-negative breast cancer development.

Despite presenting a worse prognosis and being associated with highly aggressive tumors, triple-negative breast cancer (TNBC) is characterized by the higher frequency of tumor-infiltrating lymphocytes, which have been implicated in better overall survival and response to therapy. Though recent studies have reported the capacity of B lymphocytes to recognize overly-expressed normal proteins, and tumor-associated antigens, how tumor development potentially modifies B cell response is yet to be elucidated. Our findings reveal distinct effects of 4T1 and E0771 murine tumor development on B cells in secondary lymphoid organs. Notably, we observe a significant expansion of total B cells and plasma cells in the tumor-draining lymph nodes (tDLNs) as early as 7 days after tumor challenge in both murine models, whereas changes in the spleen are less pronounced. Surprisingly, within the tumor microenvironment (TME) of both models, we detect distinct B cell subpopulations, but tumor development does not appear to cause major alterations in their frequency over time. Furthermore, our investigation into B cell regulatory phenotypes highlights that the B10 Breg phenotype remains unaffected in the evaluated tissues. Most importantly, we identified an increase in CD19 + LAG-3 + cells in tDLNs of both murine models. Interestingly, although CD19 + LAG-3 + cells represent a minor subset of total B cells (< 3%) in all evaluated tissues, most of these cells exhibit elevated expression of IgD, suggesting that LAG-3 may serve as an activation marker for B cells. Corroborating with these findings, we detected distinct cell cycle and proliferation genes alongside LAG-3 analyzing scRNA-Seq data from a cohort of TNBC patients. More importantly, our study suggests that the presence of LAG-3 B cells in breast tumors could be associated with a good prognosis, as patients with higher levels of LAG-3 B cell transcripts had a longer progression-free interval (PFI). This novel insight could pave the way for targeted therapies that harness the unique properties of LAG-3 + B cells, potentially offering new avenues for improving patient outcomes in TNBC. Further research is warranted to unravel the mechanistic pathways of these cells and to validate their prognostic value in larger, diverse patient cohorts.

Poly I:C elicits broader and stronger humoral and cellular responses to a Plasmodium vivax circumsporozoite protein malaria vaccine than Alhydrogel in mice.

Malaria remains a global health challenge, necessitating the development of effective vaccines. The RTS,S vaccination prevents Plasmodium falciparum (Pf) malaria but is ineffective against Plasmodium vivax (Pv) disease. Herein, we evaluated the murine immunogenicity of a recombinant PvCSP incorporating prevalent polymorphisms, adjuvanted with Alhydrogel or Poly I:C. Both formulations induced prolonged IgG responses, with IgG1 dominance by the Alhydrogel group and high titers of all IgG isotypes by the Poly I:C counterpart. Poly I:C-adjuvanted vaccination increased splenic plasma cells, terminally-differentiated memory cells (MBCs), and precursors relative to the Alhydrogel-combined immunization. Splenic B-cells from Poly I:C-vaccinated mice revealed an antibody-secreting cell- and MBC-differentiating gene expression profile. Biological processes such as antibody folding and secretion were highlighted by the Poly I:C-adjuvanted vaccination. These findings underscore the potential of Poly I:C to strengthen immune responses against Pv malaria.

Case report: Primary CDK4/6 inhibitor and endocrine therapy in locally advanced breast cancer and its effect on gut and intratumoral microbiota.

Locally advanced breast cancer poses significant challenges to the multidisciplinary team, in particular with hormone receptor (HR) positive, HER2-negative tumors that classically yield lower pathological complete responses with chemotherapy. The increasingly significant use of CDK 4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) in different breast cancer settings has led to clinical trials focusing on this strategy as a primary treatment, with promising results. The impact of the microbiota on cancer, and vice-versa, is an emerging topic in oncology. The authors report a clinical case of a postmenopausal female patient with an invasive breast carcinoma of the right breast, Luminal B-like, staged as cT4cN3M0 (IIIB). Since the lesion was considered primarily inoperable, the patient started letrozole and ribociclib. Following 6 months of systemic therapy, the clinical response was significant, and surgery with curative intent was performed. The final staging was ypT3ypN2aM0, R1, and the patient started adjuvant letrozole and radiotherapy. This case provides important insights on primary CDK4/6i plus ET in locally advanced unresectable HR+/HER2- breast cancer and its potential implications in disease management further ahead. The patient's gut microbiota was analyzed throughout the disease course and therapeutic approach, evidencing a shift in gut microbial dominance from Firmicutes to Bacteroidetes and a loss of microbial diversity following 6 months of systemic therapy. The analysis of the intratumoral microbiota from the surgical specimen revealed high microbial dissimilarity between the residual tumor and respective margins.