Affinity-Restricted Memory B Cells Dominate Recall Responses to Heterologous Flaviviruses.

Memory B cells (MBCs) can respond to heterologous antigens either by molding new specificities through secondary germinal centers (GCs) or by selecting preexisting clones without further affinity maturation. To distinguish these mechanisms in flavivirus infections and immunizations, we studied recall responses to envelope protein domain III (DIII). Conditional deletion of activation-induced cytidine deaminase (AID) between heterologous challenges of West Nile, Japanese encephalitis, Zika, and dengue viruses did not affect recall responses. DIII-specific MBCs were contained mostly within the plasma-cell-biased CD80+ subset, and few GCs arose following heterologous boosters, demonstrating that recall responses are confined by preexisting clonal diversity. Measurement of monoclonal antibody (mAb) binding affinity to DIII proteins, timed AID deletion, single-cell RNA sequencing, and lineage tracing experiments point to selection of relatively low-affinity MBCs as a mechanism to promote diversity. Engineering immunogens to avoid this MBC diversity may facilitate flavivirus-type-specific vaccines with minimized potential for infection enhancement.

Modeling endosymbioses: Insights and hypotheses from theoretical approaches.

Endosymbiotic relationships are pervasive across diverse taxa of life, offering key avenues for eco-evolutionary dynamics. Although a variety of experimental and empirical frameworks have shed light on critical aspects of endosymbiosis, theoretical frameworks (mathematical models) are especially well-suited for certain tasks. Mathematical models can integrate multiple factors to determine the net outcome of endosymbiotic relationships, identify broad patterns that connect endosymbioses with other systems, simplify biological complexity, generate hypotheses for underlying mechanisms, evaluate different hypotheses, identify constraints that limit certain biological interactions, and open new lines of inquiry. This Essay highlights the utility of mathematical models in endosymbiosis research, particularly in generating relevant hypotheses. Despite their limitations, mathematical models can be used to address known unknowns and discover unknown unknowns.

Lung surfactant negatively affects the photodynamic inactivation of bacteria-in vitro and molecular dynamic simulation analyses.

In the context of the rapid increase of antibiotic-resistant infections, in particular of pneumonia, antimicrobial photodynamic therapy (aPDT), the microbiological application of photodynamic therapy (PDT), comes in as a promising treatment alternative since the induced damage and resultant death are not dependent on a specific biomolecule or cellular pathway. The applicability of aPDT using the photosensitizer indocyanine green with infrared light has been successfully demonstrated for different bacterial agents in vitro, and the combination of pulmonary delivery using nebulization and external light activation has been shown to be feasible. However, there has been little progress in obtaining sufficient in vivo efficacy results. This study reports the lung surfactant as a significant suppressor of aPDT in the lungs. In vitro, the clinical surfactant Survanta® reduced the aPDT effect of indocyanine green, Photodithazine®, bacteriochlorin-trizma, and protoporphyrin IX against Streptococcus pneumoniae. The absorbance and fluorescence spectra, as well as the photobleaching profile, suggested that the decrease in efficacy is not a result of singlet oxygen quenching, while a molecular dynamics simulation showed an affinity for the polar head groups of the surfactant phospholipids that likely impacts uptake of the photosensitizers by the bacteria. Methylene blue is the exception, likely because its high water solubility confers a higher mobility when interacting with the surfactant layer. We propose that the interaction between lung surfactant and photosensitizer must be taken into account when developing pulmonary aPDT protocols.

Acute Ethanol Modulates Synaptic Inhibition in the Basolateral Amygdala via Rapid NLRP3 Inflammasome Activation and Regulates Anxiety-Like Behavior in Rats.

Chronic alcohol exposure leads to a neuroinflammatory response involving activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome and proinflammatory cytokine production. Acute ethanol (EtOH) exposure activates GABAergic synapses in the central and basolateral amygdala (BLA) ex vivo, but whether this rapid modulation of synaptic inhibition is because of an acute inflammatory response and alters anxiety-like behavior in male and female animals is not known. Here, we tested the hypotheses that acute EtOH facilitates inhibitory synaptic transmission in the BLA by activating the NLRP3 inflammasome-dependent acute inflammatory response, that the alcohol-induced increase in inhibition is cell type and sex dependent, and that acute EtOH in the BLA reduces anxiety-like behavior. Acute EtOH application at a binge-like concentration (22-44 mm) stimulated synaptic GABA release from putative parvalbumin (PV) interneurons onto BLA principal neurons in ex vivo brain slices from male, but not female, rats. The EtOH facilitation of synaptic inhibition was blocked by antagonists of the Toll-like receptor 4 (TLR4), the NLRP3 inflammasome, and interleukin-1 receptors, suggesting it was mediated by a rapid local neuroinflammatory response in the BLA. In vivo, bilateral injection of EtOH directly into the BLA produced an acute concentration-dependent reduction in anxiety-like behavior in male but not female rats. These findings demonstrate that acute EtOH in the BLA regulates anxiety-like behavior in a sex-dependent manner and suggest that this effect is associated with presynaptic facilitation of parvalbumin-expressing interneuron inputs to BLA principal neurons via a local NLRP3 inflammasome-dependent neuroimmune response.SIGNIFICANCE STATEMENT Chronic alcohol exposure produces a neuroinflammatory response, which contributes to alcohol-associated pathologies. Acute alcohol administration increases inhibitory synaptic signaling in the brain, but the mechanism for the rapid alcohol facilitation of inhibitory circuits is unknown. We found that acute ethanol at binge-like concentrations in the basolateral amygdala (BLA) facilitates GABA release from parvalbumin-expressing (PV) interneuron synapses onto principal neurons in ex vivo brain slices from male rats and that intra-BLA ethanol reduces anxiety-like behavior in vivo in male rats, but not female rats. The ethanol (EtOH) facilitation of inhibition in the BLA is mediated by Toll-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation and proinflammatory IL-1ß signaling, which suggests a rapid NLRP3 inflammasome-dependent neuroimmune cascade that plays a critical role in acute alcohol intoxication.

Role of corticotropin-releasing factor neurotransmission in the lateral hypothalamus on baroreflex impairment evoked by chronic variable stress in rats.

Despite the importance of physiological responses to stress in a short-term, chronically these adjustments may be harmful and lead to diseases, including cardiovascular diseases. The lateral hypothalamus (LH) has been reported to be involved in expression of physiological and behavioral responses to stress, but the local neurochemical mechanisms involved are not completely described. The corticotropin-releasing factor (CRF) neurotransmission is a prominent brain neurochemical system implicated in the physiological and behavioral changes induced by aversive threats. Furthermore, chronic exposure to aversive situations affects the CRF neurotransmission in brain regions involved in stress responses. Therefore, in this study, we evaluated the influence of CRF neurotransmission in the LH on changes in cardiovascular function and baroreflex activity induced by chronic variable stress (CVS). We identified that CVS enhanced baseline arterial pressure and impaired baroreflex function, which were followed by increased expression of CRF2, but not CRF1, receptor expression within the LH. Local microinjection of either CRF1 or CRF2 receptor antagonist within the LH inhibited the baroreflex impairment caused by CVS, but without affecting the mild hypertension. Taken together, the findings documented in this study suggest that LH CRF neurotransmission participates in the baroreflex impairment related to chronic stress exposure.

Tannic acid: A possible therapeutic agent for hypermethioninemia-induced neurochemical changes in young rats.

This study explores the therapeutic benefits of tannic acid (TnA) in an experimental protocol of chronic hypermethioninemia in rats. Rats were categorized into four groups: Group I - control, Group II - TnA 30 mg/kg, Group III - methionine (Met) 0.2-0.4 g/kg + methionine sulfoxide (MS) 0.05-0.1 g/kg, Group IV - TnA/Met + MS. Saline was administered by subcutaneous pathway into groups I and II twice daily from postnatal day 6 (P6) to P28, whereas those in groups III and IV received Met + MS. From P28 to P35, groups II and IV received TnA orally. Animals from group III presented cognitive and memory impairment assessed through object recognition and Y-maze tests (p < 0.05). Elevated levels of reactive species, lipid peroxidation, and nitrites followed by a decline in sulfhydryl content, catalase activity, and superoxide dismutase activity were observed in animals treated with Met + MS (p < 0.05). However, TnA treatment reversed all these effects (p < 0.05). In group III, there was an increase in acetylcholinesterase activity and IL-6 levels, coupled with a reduction in Na+/K+-ATPase activity (p < 0.05). TnA was able to protect against these effects (p < 0.05). The gene expression of catalase, brain-derived neurotrophic factor, and nuclear factor erythroid 2-related factor 2 was decreased in the hippocampus and striatum from group III (p < 0.05). TnA reversed almost all of these alterations (p < 0.05). These findings suggest that TnA is a therapeutic target for patients with hypermethioninemia.

IL-27-engineered CAR.19-NK-92 cells exhibit enhanced therapeutic efficacy.

Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells has shown promising results in early-phase clinical studies. However, advancing CAR-NK cell therapeutic efficacy is imperative. In this study, we investigated the impact of a fourth-generation CD19-targeted CAR (CAR.19) coexpressing IL-27 on NK-92 cells. We observed a significant improvement in NK-92 cell proliferation and cytotoxicity activity against B-cell cancer cell lines, both in vitro and in a xenograft mouse B-cell lymphoma model. Our systematic transcriptome analysis of the activated NK-92 CAR variants further supports the potential of IL-27 in fourth-generation CARs to overcome limitations of NK cell-based targeted tumor therapies by providing essential growth and activation signals. Integrating IL-27 into CAR-NK cells emerges as a promising strategy to enhance their therapeutic potential and elicit robust responses against cancer cells. These findings contribute substantially to the mounting evidence supporting the potential of fourth-generation CAR engineering in advancing NK cell-based immunotherapies.

Granulomatous meningoencephalitis and blindness associated with Mycobacterium tuberculosis complex infection in a senile female chimpanzee (Pan troglodytes).

A 40-year old female chimpanzee (Pan troglodytes) developed hyporexia, weight loss, followed by progressive and complete blindness. Tomography demonstrated an intracranial mass in the rostroventral brain involving the optic chiasm, with a presumptive diagnosis of neoplasm. However, histopathology revealed a granulomatous meningoencephalitis, and tissue samples tested positive for Mycobacterium tuberculosis.

Staphylococcus spp. as part of the microbiota and as opportunistic pathogen in free-ranging black-tuffed marmosets (Callithrix penicillata) from urban areas: Epidemiology, antimicrobial resistance, and pathology.

BACKGROUND: Marmosets (Callithrix sp.), including black-tuffed marmosets (C. penicillata), are neotropical primates that can be highly adapted to urban environments, especially parks and forested areas near cities. Staphylococcus spp. are part of the microbiota of many different hosts and lead to opportunistic severe infection. Isolates from wild animals can be resistant to antimicrobial drugs. However, there are a few studies that evaluated Staphylococcus spp. in neotropical primates. The goal of this study was to evaluate Staphylococcus spp. isolated from free-ranging black-tuffed marmosets. METHODS: Marmosets were captured in six urban parks. After sedation, skin and rectal swabs and feces were sampled. Staphylococcus spp. isolates were identified by MALDI-ToF and their antimicrobial susceptibility was determined. RESULTS: Over 30% of captured individuals were positive for Staphylococcus spp., and S. aureus was the most isolated species followed by Mammaliicoccus (Staphylococcus) sciuri. With the exception of the marmoset subjected to necropsy, none of the other had lesions, which supports that notion that Staphylococcus spp. are members of the microbiota, but also opportunistic pathogens. Most isolates were susceptible to all antimicrobials tested; however, one isolate of S. epidermidis was resistant to multiple antimicrobials (penicillin, cefoxitin, ciprofloxacin, clindamycin, and erythromycin). We considered S. aureus as the main staphylococci to colonize black-tuffed marmosets. CONCLUSIONS: Black-tuffed marmosets can be colonized by several Staphylococcus species, most frequently by S. aureus, and the majority of isolates were sensible to the antimicrobials tested. One S. epidermidis isolate was considered multidrug resistant.

Discovery of pyrazolo[3,4-d]pyrimidines as novel mitogen-activated protein kinase kinase 3 (MKK3) inhibitors.

The dual-specificity protein kinase MKK3 has been implicated in tumor cell proliferation and survival, yet its precise role in cancer remains inconclusive. A critical step in elucidating the kinase's involvement in disease biology is the identification of potent, cell-permeable kinase inhibitors. Presently, MKK3 lacks a dedicated tool compound for these purposes, along with validated methods for the facile screening, identification, and optimization of inhibitors. In this study, we have developed a TR-FRET-based enzymatic assay for the detection of MKK3 activity in vitro and a BRET-based assay to assess ligand binding to this enzyme within intact human cells. These assays were instrumental in identifying hit compounds against MKK3 that share a common chemical scaffold, sourced from a library of bioactive kinase inhibitors. Initial hits were subsequently expanded through the synthesis of novel analogs. The resulting structure-activity relationship (SAR) was rationalized using molecular dynamics simulations against a homology model of MKK3. We expect our findings to expedite the development of novel, potent, selective, and bioactive inhibitors, thus facilitating investigations into MKK3's role in various cancers.

Oral manifestations of amyloidosis and the diagnostic applicability of oral tissue biopsy.

BACKGROUND: Amyloidosis exhibits a variable spectrum of systemic signs and oral manifestations that can be difficult to diagnose. This study aimed to characterize the clinical, demographic, and microscopic features of amyloidosis in the oral cavity. METHODS: This collaborative study involved three Brazilian oral pathology centers and described cases with a confirmed diagnosis of amyloidosis on available oral tissue biopsies. Clinical data were obtained from medical records. H&E, Congo-red, and immunohistochemically stained slides were analyzed. RESULTS: Twenty-six oral biopsies from 23 individuals (65.2% males; mean age: 59.6 years) were included. Oral involvement was the first sign of the disease in 67.0% of cases. Two patients had no clinical manifestation in the oral mucosa, although the histological analysis confirmed amyloid deposition. Amyloid deposits were distributed in perivascular (88.0%), periacinar and periductal (80.0%), perineurial (80.0%), endoneurial (33.3%), perimuscular (88.2%), intramuscular (94.1%), and subepithelial (35.3%) sites as well as around fat cells (100.0%). Mild/moderate inflammation was found in 65.4% of cases and 23.1% had giant cells. CONCLUSIONS: Amyloid deposits were consistently found in oral tissues, exhibiting distinct deposition patterns. Oral biopsy is less invasive than internal organ biopsy and enables the reliable identification of amyloid deposits even in the absence of oral manifestations. These findings corroborate the relevance of oral biopsy for the diagnosis of amyloidosis.

Sex-specific negative affect-like behaviour and parabrachial nucleus activation induced by BNST stimulation in adult mice with adolescent alcohol history.

Adolescent alcohol use is a strong predictor for the subsequent development of alcohol use disorders later in life. Additionally, adolescence is a critical period for the onset of affective disorders, which can contribute to problematic drinking behaviours and relapse, particularly in females. Previous studies from our laboratory have shown that exposure to adolescent intermittent ethanol (AIE) vapour alters glutamatergic transmission in the bed nucleus of the stria terminalis (BNST) and, when combined with adult stress, elicits sex-specific changes in glutamatergic plasticity and negative affect-like behaviours in mice. Building on these findings, the current work investigated whether BNST stimulation could substitute for stress exposure to increase the latency to consume a palatable food in a novel context (hyponeophagia) and promote social avoidance in adult mice with AIE history. Given the dense connections between the BNST and the parabrachial nucleus (PBN), a region involved in mediating threat assessment and feeding behaviours, we hypothesized that increased negative affect-like behaviours would be associated with PBN activation. Our results revealed that the chemogenetic stimulation of the dorsolateral BNST induced hyponeophagia in females with AIE history, but not in female controls or males of either group. Social interaction remained unaffected in both sexes. Notably, this behavioural phenotype was associated with higher activation of calcitonin gene-related peptide and dynorphin cells in the PBN. These findings provide new insights into the neurobiological mechanisms underlying the development of negative affect in females and highlight the potential involvement of the BNST-PBN circuitry in regulating emotional responses to alcohol-related stimuli.

Enteropathogenic Escherichia coli modulates the virulence and pathogenicity of Entamoeba dispar.

Amoebiasis is a disease caused by Entamoeba histolytica, affecting the large intestine of humans and occasionally leading to extra-intestinal lesions. Entamoeba dispar is another amoeba species considered commensal, although it has been identified in patients presenting with dysenteric and nondysenteric colitis, as well as amoebic liver abscess. Amoebic virulence factors are essential for the invasion and development of lesions. There is evidence showing that the association of enterobacteria with trophozoites contributes to increased gene expression of amoebic virulence factors. Enteropathogenic Escherichia coli is an important bacterium causing diarrhea, with high incidence rates in the world population, allowing it to interact with Entamoeba sp. in the same host. In this context, this study aims to evaluate the influence of enteropathogenic Escherichia coli on ACFN and ADO Entamoeba dispar strains by quantifying the gene expression of virulence factors, including galactose/N-acetyl-D-galactosamine-binding lectin, cysteine proteinase 2, and amoebapores A and C. Additionally, the study assesses the progression and morphological aspect of amoebic liver abscess and the profile of inflammatory cells. Our results demonstrated that the interaction between EPEC and ACFN Entamoeba dispar strains was able to increase the gene expression of virulence factors, as well as the lesion area and the activity of the inflammatory infiltrate. However, the association with the ADO strain did not influence the gene expression of virulence factors. Together, our findings indicate that the interaction between EPEC, ACFN, and ADO Entamoeba dispar strains resulted in differences in vitro and in vivo gene expression of Gal/GalNAc-binding lectin and CP2, in enzymatic activities of MPO, NAG, and EPO, and consequently, in the ability to cause lesions.

Strategies for involving patients and the public in scaling initiatives in health and social services: A scoping review.

BACKGROUND: Scaling in health and social services (HSS) aims to increase the intended impact of proven effective interventions. Patient and public involvement (PPI) is critical for ensuring that scaling beneficiaries' interests are served. We aimed to identify PPI strategies and their characteristics in the science and practice of scaling in HSS. METHODS: In this scoping review, we included any scaling initiative in HSS that used PPI strategies and reported PPI methods and outcomes. We searched electronic databases (e.g., Medline) from inception to 5 February 2024, and grey literature (e.g., Google). Paired reviewers independently selected and extracted eligible reports. A narrative synthesis was performed and we used the PRISMA for Scoping Reviews and the Guidance for Reporting Involvement of Patients and the Public (GRIPP2). FINDINGS: We included 110 unique reports out of 24,579 records. In the past 5 years, the evidence on PPI in scaling has increased faster than in any previous period. We found 236 mutually nonexclusive PPI strategies among 120 scaling initiatives. Twenty-four initiatives did not target a specific country; but most of those that did so (n = 96) occurred in higher-income countries (n = 51). Community-based primary health care was the most frequent level of care (n = 103). Mostly, patients and the public were involved throughout all scaling phases (n = 46) and throughout the continuum of collaboration (n = 45); the most frequently reported ethical lens regarding the rationale for PPI was consequentialist-utilitarian (n = 96). Few papers reported PPI recruitment processes (n = 31) or incentives used (n = 18). PPI strategies occurred mostly in direct care (n = 88). Patient and public education was the PPI strategy most reported (n = 31), followed by population consultations (n = 30). CONCLUSIONS: PPI in scaling is increasing in HSS. Further investigation is needed to better document the PPI experience in scaling and ensure that it occurs in a meaningful and equitable way. PATIENT AND PUBLIC CONTRIBUTION: Two patients were involved in this review. They shared decisions on review questions, data collection instruments, protocol design, and findings dissemination. REVIEW REGISTRATION: Open Science Framework on 19 August 2020 (https://osf.io/zqpx7/).

Changes in intention to use an interprofessional approach to decision-making following training: a cluster before-and-after study.

BACKGROUND: Health professionals in home care work in interprofessional teams. Yet most training in decision support assumes a one-on-one relationship with patients. We assessed the impact of an in-person training session in interprofessional shared decision-making (IP-SDM) on home care professionals' intention to adopt this approach. METHODS: We conducted a secondary analysis of a cluster stepped-wedge trial using a before-and-after study design. We collected data among home care professionals from November 2016 to February 2018 in 9 health and social services centers in Quebec, Canada. The intervention was an in-person IP-SDM training session. Intention to engage in IP-SDM pre- and post-session (dependent variable) was compared using a continuing professional development evaluation scale (CPD-Reaction) informed by the Godin's Integrated Behavioral Model for health professionals. We also assessed socio-demographic and psychosocial variables (beliefs about capabilities, beliefs about consequences, social influence and moral norm). We performed bivariate and multivariate analysis to identify factors influencing post-intervention intention. We used the STROBE reporting guidelines for observational studies to report our results. RESULTS: Of 134 respondents who provided complete pairs of questionnaires (pre- and post-), most were female (90.9%), mean age was 42 (± 9.3) years and 66.9% were social workers. Mean intention scores decreased from 5.84 (± 1.19) to 5.54 (± 1.35) (Mean difference = -0.30 ± 1.16; p = 0.02). Factors associated with higher intention post-intervention were social influence (ß = 0.34, p = 0.01) and belief about capabilities (ß = 0.49, p < 0.01). CONCLUSION: After in-person IP-SDM training, healthcare professionals' intention to engage in IP-SDM decreased. However, the scope of this decrease is probably not clinically significant. Due to their association with intention, beliefs about capabilities, which translate into having a sense of self-competency in the new clinical behavior, and social influences, which translate into what important others think one should be doing, could be targets for future research aiming to implement IP-SDM in home care settings.

Leishmania (Leishmania) infantum DNA detection in Nyssomyia neivai in Vale do Ribeira, Paraná, Brazil.

BACKGROUND: The incidence of visceral leishmaniasis (VL) has increased in the Southern region of Brazil in recent years, especially in the State of Paraná. New species have been suggested with potential to act as vector in VL endemic areas. OBJECTIVES: Identify the Leishmania species in sand fly specimens collected from 2016 to 2018 in the municipality of Itaperuçu, Vale do Ribeira, Paraná, Brazil. METHODS: Light traps were used for collections and for the analysis of sand fly were used the multiplex polymerase chain reaction (PCR) methodology and subsequent sequencing. FINDINGS: Among the collected specimens, 88.62% were attributed to the species Nyssomyia neivai, which were grouped into 176 pools. Three positive pools were detected: two with Leishmania (Viannia) braziliensis and one with L. (Leishmania) infantum. The positivity rate for the parasite was 0.25% based on the presence of at least one infected insect in the pool. MAIN CONCLUSIONS: The detection of L. infantum in Ny. neivai draws attention due to its abundance and anthropophily in the State of Paraná. Moreover, this finding is considered as an alert and suggests that the vector competence of Ny. neivai and the criteria for its incrimination should be carried out, given its wide distribution in southern of Brazil.

Validation of qPCR reference genes in the endangered annual killifish Austrolebias charrua considering different tissues, gender and environmental conditions.

The annual killifish Austrolebias charrua is an endangered species, endemic to the southern region of South America, which inhabits temporary ponds that emerges in the rainy season. The main anthropogenic threat driving the extinction of A. charrua stems from extensive agriculture, primarily due to the widrespread use of glyphosate-based herbicides near their habitats. Annual killifishes have been used as models for ecotoxicological studies but, up to now, there are no studies about reference genes in any Austrolebias species. This represents an obstacle to the use of qPCR-based technologies, the standard method for gene expression quantification. The present study aimed to select and validate potential reference genes for qPCR normalization in the annual killifish Austrolebias charrua considering different tissues, gender and environmental conditions. The candidate reference genes 18 s, actb, gapdh, ef1a, shox, eif3g, and the control gene atp1a1 were evaluated in male and female individuals in three different tissues (brain, liver, and gills) under two experimental conditions (control and acute exposition to Roundup Transorb®). The collected tissues were submitted to RNA extraction, followed by cDNA synthesis, cloning, sequencing, and qPCR. Overall, 18 s was the most stable reference gene, and 18 s and ef1a were the most stable combination. Otherwise, considering all variables, gapdh and shox were the least stable candidate genes. Foremost, suitable reference genes were validated in A. charrua, facilitating accurate mRNA quantification in this species, which might be useful for developing molecular tools of ecotoxicological assessment based on gene expression analysis for environmental monitoring of annual killifish.

ChatGPT and dentistry: a step toward the future.

This article aims to explore the integration of ChatGPT, an advanced conversational artificial intelligence model, in the field of dentistry. The review primarily consists of information related to the capabilities and functionalities of ChatGPT and how these abilities can aid dental professionals. This study includes data from research papers, case studies, and relevant literature on language models, as well as papers on dentistry, patient communication, dental education, and clinical decision-making. A systematic approach was used to select relevant studies and literature. The selection criteria focused on papers that specifically discussed the integration of language models, ChatGPT in particular, in dentistry and their applications. The study findings revealed that ChatGPT has significant potential to revolutionize dentistry by offering various applications and benefits. It can enhance patient engagement and understanding through personalized oral health information and guidance. In dental education, ChatGPT can provide interactive learning, case studies, and virtual patient simulations. ChatGPT can also assist researchers in analyzing dental literature, identifying patterns, and generating insights. Moreover, it supports dentists with evidence-based recommendations, treatment options, and diagnostic support. Integrating ChatGPT in dentistry can be highly beneficial, but it is crucial to address ethical considerations, accuracy, and privacy concerns. Responsible implementation and continuous improvement of its functionalities are necessary to ensure that patient care and outcomes are improved.

Angiotensinergic neurotransmission in the bed nucleus of the stria terminalis is involved in cardiovascular responses to acute restraint stress in rats.

The brain angiotensin II acting via AT1 receptors is a prominent mechanism involved in physiological and behavioral responses during aversive situations. The AT2 receptor has also been implicated in stress responses, but its role was less explored. Despite these pieces of evidence, the brain sites related to control of the changes during aversive threats by the brain renin-angiotensin system (RAS) are poorly understood. The bed nucleus of the stria terminalis (BNST) is a limbic structure related to the cardiovascular responses by stress, and components of the RAS system were identified in this forebrain region. Therefore, we investigated the role of angiotensinergic neurotransmission present within the BNST acting via local AT1 and AT2 receptors in cardiovascular responses evoked by an acute session of restraint stress in rats. For this, rats were subjected to bilateral microinjection of either the angiotensin-converting enzyme inhibitor captopril, the selective AT1 receptor antagonist losartan, or the selective AT2 receptor antagonist PD123319 before they underwent the restraint stress session. We observed that BNST treatment with captopril reduced the decrease in tail skin temperature evoked by restraint stress, without affecting the pressor and tachycardic responses. Local AT2 receptor antagonism within the BNST reduced both the tachycardia and the drop in tail skin temperature during restraint. Bilateral microinjection of losartan into the BNST did not affect the restraint-evoked cardiovascular changes. Taken together, these data indicate an involvement of BNST angiotensinergic neurotransmission acting via local AT2 receptors in cardiovascular responses during stressful situations.

Open questions in the social lives of viruses.

Social interactions among viruses occur whenever multiple viral genomes infect the same cells, hosts, or populations of hosts. Viral social interactions range from cooperation to conflict, occur throughout the viral world, and affect every stage of the viral lifecycle. The ubiquity of these social interactions means that they can determine the population dynamics, evolutionary trajectory, and clinical progression of viral infections. At the same time, social interactions in viruses raise new questions for evolutionary theory, providing opportunities to test and extend existing frameworks within social evolution. Many opportunities exist at this interface: Insights into the evolution of viral social interactions have immediate implications for our understanding of the fundamental biology and clinical manifestation of viral diseases. However, these opportunities are currently limited because evolutionary biologists only rarely study social evolution in viruses. Here, we bridge this gap by (1) summarizing the ways in which viruses can interact socially, including consequences for social evolution and evolvability; (2) outlining some open questions raised by viruses that could challenge concepts within social evolution theory; and (3) providing some illustrative examples, data sources, and conceptual questions, for studying the natural history of social viruses.