Using cocrystals as a tool to study non-crystallizing molecules: crystal structure, Hirshfeld surface analysis and computational study of the 1:1 cocrystal of (E)-N-(3,4-difluorophenyl)-1-(pyridin-4-yl)methanimine and acetic acid.

Using a 1:1 cocrystal of (E)-N-(3,4-difluorophenyl)-1-(pyridin-4-yl)methanimine with acetic acid, C12H8F2N2·C2H4O2, we investigate the influence of F atoms introduced to the aromatic ring on promoting π-π interactions. The cocrystal crystallizes in the triclinic space group P1. Through crystallographic analysis and computational studies, we reveal the molecular arrangement within this cocrystal, demonstrating the presence of hydrogen bonding between the acetic acid molecule and the pyridyl group, along with π-π interactions between the aromatic rings. Our findings highlight the importance of F atoms in promoting π-π interactions without necessitating full halogenation of the aromatic ring.

An integrative review of parent education approaches in sport: Considerations for program planning and evaluation.

In recent years, there has been an increase in the delivery and evaluation of parent education programs within youth sport. Subsequently, some recent reviews of these programs have been conducted. However, one consistent issue across many of the programs and associated review papers is the lack of an appropriate evaluation framework to guide the planning or associated reporting of the outcomes of the interventions. This has limited understanding of the overall impact of sport parenting interventions. Thus, the purposes of the current study were as follows: (a) to identify commonalities in the reporting and evaluation of parent education programs; (b) to identify gaps in the reporting and evaluation of parent education programs; (c) to draw these insights together to provide suggestions regarding how the RE-AIM could be used to enhance planning and evaluation of evidence-based programs for parent education in sport. Specifically, utilizing the RE-AIM framework to provide insights into pertinent evaluation metrics, this integrative review aimed to identify commonalities and gaps in the reporting of parent education programs. The RE-AIM framework considers the essential elements to assess the external and internal validity of interventions through five dimensions: Reach, Effectiveness, Adoption, Implementation, and Maintenance (Am J Public Health. 1999;89(9):1322-1327). Subsequently, the review aimed to provide suggestions regarding strategies to enhance the planning and evaluation of evidence-based programs for parent education in sport. Overall, the analysis demonstrated that most studies presented some pertinent evaluation information related to the RE-AIM framework, such as the number of participants and contacts made, the measures used, and the program level. However, the studies also lacked information on participant exclusion criteria, the method used to select the delivery agent (e.g., parents engaged in the program), and cost measures. Overall, the current study identified various areas where programs could be enhanced, specifically related to reporting procedural elements (e.g., program design, target population, and costs) pertaining to the implementation of parent education programs.

Assessing the implementation of a multi-component hypertension program in a Guatemalan under-resourced dynamic context: an application of the RE-AIM/PRISM extension for sustainability and health equity.

BACKGROUND: The COVID-19 pandemic necessitated rapid changes in healthcare delivery in Guatemala's public primary care settings. A new hypertension program, implemented as part of a type 2 hybrid trial since 2019, exemplifies an implementation effort amidst a changing context in an under-resourced setting. We assessed the implementation of an evidence-based intervention (EBI; protocol-based hypertension treatment) and one of its main implementation strategies (team-based collaborative care), raising implications for health equity and sustainability. We present innovative application of systems thinking visuals. METHODS: Conducting a convergent mixed methods analysis, we assessed implementation in response to contextual changes across five Ministry of Health (MoH) districts at the pandemic's onset. Utilizing quantitative programmatic data and qualitative interviews with stakeholders (n=18; health providers, administrators, study staff), we evaluated dimensions of "Reach, Effectiveness, Adoption, Implementation and Maintenance," RE-AIM (Reach, Implementation delivery + adaptations), and "Practical Robust Implementation and Sustainability Model," PRISM (Organizational perspective on the EBI, Fit, Implementation and sustainability infrastructure) frameworks. We assessed representativeness by comparing participants to census data. To assess implementation delivery, we built behavior-over-time (BOT) graphs with quantitative programmatic data (July 2019-July 2021). To assess adaptations and contextual changes, we performed matrix-based thematic qualitative analysis. We converged quantitative implementation delivery data + qualitative adaptations data in joint displays. Finally, we analyzed qualitative and quantitative results across RE-AIM/PRISM and health districts to identify equity and sustainability considerations. RESULTS: Contextual factors that facilitated program delivery included the perception that the EBI was beneficial, program champions, and staff communication. Key barriers to implementation delivery included competition with other primary care activities and limited implementation infrastructure (e.g., equipment, medications). Contextual changes related to COVID-19 hindered implementation delivery, threatened sustainability, and may have exacerbated inequities. However, adaptations that were planned enhanced implementation delivery and may have supported improved equity and sustainability. CONCLUSIONS: Recognition of an EBI's benefits and program champions are important for supporting initial uptake. The ability to plan adaptations amid rapid contextual changes has potential advantages for sustainability and equitable delivery. Systems thinking tools and mixed methods approaches may shed light on the relations between context, adaptations, and equitable and sustainable implementation. TRIAL REGISTRATION: NCT03504124.

Pnictogen bond-driven control of the molecular interaction between organophosphorus and acetylcholinesterase enzyme.

This study addresses a comprehensive assessment of the interaction between chemical warfare agents (CWA) and acetylcholinesterase (AChE) systems, focus on the intriguing pnictogen-bond interaction (PnB). Utilizing the crystallographic data from the Protein Data Bank pertaining to the AChE-CWA complex involving Sarin (GB), Cyclosarin (GF), 2-[fluoro(methyl)phosphoryl]oxy-1,1-dimethylcyclopentane (GP) and venomous agent X (VX) agents, the CWA is systematically displaced by increments of 0.1 Å along the PO bond axis, extending its distance by 4 Å from the original position. The AIM analysis was carried out and consistently revealed the presence of a significant interaction along the PO bond. Investigating the intrinsic nature of the PnB, the NBO and the EDA analysis unearthed the contribution of orbital factors to the overall energy of the system. Strikingly, this observation challenges the conventional σ-hole explanation commonly associated with such interactions. This finding adds a layer of complexity to understanding of PnB, encouraging further exploration into the underlying mechanisms governing these intriguing chemical phenomena.

Implementation of the Baby-Friendly Hospital Initiative in Mexico: a systematic literature review using the RE-AIM framework.

The Baby-Friendly Hospital Initiative (BFHI) is a global strategy to encourage health facilities to promote, support, and protect breastfeeding by implementing a package of policies and practices known as the Ten Steps to Successful Breastfeeding. Prior studies have found that implementing the Ten Steps has a positive impact on breastfeeding outcomes. Yet, little is known about the implementation of the Ten Steps in Mexico. The objective of this study was to conduct a systematic review to evaluate the reach, efficacy/effectiveness, adoption, implementation, and maintenance of the Ten Steps in Mexico, using the RE-AIM framework. The systematic literature review included studies published in English or Spanish without date restrictions. Two of the authors coded each of the articles through a harmonized data extraction tool, and group meetings were used to discuss any discrepancies. The reviewed data were managed in the Rayyan platform. The risk of study bias was assessed through the Johanna Briggs Institute critical appraisal checklists. Of the 1,123 articles initially identified, 6 met the review inclusion criteria. None of the articles evaluated the reach and maintenance of the Ten Steps. The articles identified major gaps in the implementation of the Ten Steps. Most of the articles had important limitations in terms of their quality. In Mexico, it is necessary to rethink the BFHI and employ multiple strategies to improve implementation of the Ten Steps, including developing transparent BFHI monitoring mechanisms that produce data on implementation and that are publicly available, as well as investing in implementation research and evaluation to generate strong evidence to support the adoption and efficient maintenance of the Ten Steps in health facilities in Mexico. When properly implemented, BFHI becomes central to promote, protect, and support breastfeeding. Therefore, it is essential for Mexico to position BFHI as a top priority of the country's public policy agenda. Systematic Review Registration: identifier: CRD42021248118.

High cell-free DNA is associated with disease progression, inflammasome activation and elevated levels of inflammasome-related cytokine IL-18 in patients with myelofibrosis.

Myelofibrosis (MF) is a clonal hematopoietic stem cell disorder classified among chronic myeloproliferative neoplasms, characterized by exacerbated myeloid and megakaryocytic proliferation and bone marrow fibrosis. It is induced by driver (JAK2/CALR/MPL) and high molecular risk mutations coupled to a sustained inflammatory state that contributes to disease pathogenesis. Patient outcome is determined by stratification into risk groups and refinement of current prognostic systems may help individualize treatment decisions. Circulating cell-free (cf)DNA comprises short fragments of double-stranded DNA, which promotes inflammation by stimulating several pathways, including inflammasome activation, which is responsible for IL-1ß and IL-18 maturation and release. In this work, we assessed the contribution of cfDNA as a marker of disease progression and mediator of inflammation in MF. cfDNA was increased in MF patients and higher levels were associated with adverse clinical outcome, a high-risk molecular profile, advanced disease stages and inferior overall survival, indicating its potential value as a prognostic marker. Cell-free DNA levels correlated with tumor burden parameters and markers of systemic inflammation. To mimic the effects of cfDNA, monocytes were stimulated with poly(dA:dT), a synthetic double-stranded DNA. Following stimulation, patient monocytes released higher amounts of inflammasome-processed cytokine, IL-18 to the culture supernatant, reflecting enhanced inflammasome function. Despite overexpression of cytosolic DNA inflammasome sensor AIM2, IL-18 release from MF monocytes was shown to rely mainly on the NLRP3 inflammasome, as it was prevented by NLRP3-specific inhibitor MCC950. Circulating IL-18 levels were increased in MF plasma, reflecting in vivo inflammasome activation, and highlighting the previously unrecognized involvement of this cytokine in MF cytokine network. Monocyte counts were higher in patients and showed a trend towards correlation with IL-18 levels, suggesting monocytes represent a source of circulating IL-18. The close correlation shown between IL-18 and cfDNA levels, together with the finding of enhanced DNA-triggered IL-18 release from monocytes, suggest that cfDNA promotes inflammation, at least in part, through inflammasome activation. This work highlights cfDNA, the inflammasome and IL-18 as additional players in the complex inflammatory circuit that fosters MF progression, potentially providing new therapeutic targets.

Molecular Factors in PAD2 (PADI2) and PAD4 (PADI4) Are Associated with Interstitial Lung Disease Susceptibility in Rheumatoid Arthritis Patients.

Around 50% of rheumatoid arthritis (RA) patients show some extra-articular manifestation, with the lung a usually affected organ; in addition, the presence of anti-citrullinated protein antibodies (ACPA) is a common feature, which is caused by protein citrullination modifications, catalyzed by the peptidyl arginine deiminases (PAD) enzymes. We aimed to identify single nucleotide variants (SNV) in PADI2 and PADI4 genes (PAD2 and PAD4 proteins, respectively) associated with susceptibility to interstitial lung disease (ILD) in RA patients and the PAD2 and PAD4 levels. Material and methods: 867 subjects were included: 118 RA-ILD patients, 133 RA patients, and 616 clinically healthy subjects (CHS). Allelic discrimination was performed in eight SNVs using qPCR, four in PADI2 and four in PADI4. The ELISA technique determined PAD2 and PAD4 levels in serum and bronchoalveolar lavage (BAL) samples, and the population structure was evaluated using 14 informative ancestry markers. Results: The rs1005753-GG (OR = 4.9) in PADI2 and rs11203366-AA (OR = 3.08), rs11203367-GG (OR = 2.4) in PADI4 are associated with genetic susceptibility to RA-ILD as well as the ACTC haplotype (OR = 2.64). In addition, the PAD4 protein is increased in RA-ILD individuals harboring the minor allele homozygous genotype in PADI4 SNVs. Moreover, rs1748033 in PADI4, rs2057094, and rs2076615 in PADI2 are associated with RA susceptibility. In conclusion, in RA patients, single nucleotide variants in PADI4 and PADI2 are associated with ILD susceptibility. The rs1748033 in PADI4 and two different SNVs in PADI2 are associated with RA development but not ILD. PAD4 serum levels are increased in RA-ILD patients.

Variants in interferon gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) genes that modulate inflammatory response are associated with periodontitis.

OBJECTIVE: Evaluate the association of genetic variants of the interferon gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) genes with periodontitis. METHODS: The study involved 117 individuals with periodontitis and 389 without periodontitis, all Brazilians, miscegenated. Individuals with periodontitis presented at least 4 teeth with ≥ 1 site with probing depth ≥ 4 mm; clinical attachment level ≥ 3 mm on the same site and bleeding upon stimulus. Genotyping was performed using the Infinium Multi-Ethnic AMR/AFR-8 Bead Chip focused on Hispanic and African American populations with approximately 2 million markers of the human genome. Multivariate logistic regression was performed to identify associations in additive, dominant and recessive models adjusted for covariates age, obesity, mouth breathing, flossing, asthma, and ancestry. RESULTS: In IFI16, the rs75985579-A is positively associated with periodontitis in the additive (Odds Ratio adjusted (ORadjusted) 2.65, 95% confidence interval (CI):1.25-5.60, p value: 0.007) and dominant models (ORadjusted 2.56, 95%CI:1.13-5.81, p value: 0.017). In AIM2, the rs76457189-G, is associated negatively with periodontitis in two genetic models evaluated, additive (ORadjusted 0.21, 95%CI:0.05-0.94, p value: 0.022) and dominant (ORadjusted 0.21, 95%CI:0.05-0.94, p value: 0.022). CONCLUSIONS: These results have shown that variants in the IFI16 and AIM2 genes are associated with periodontitis. Individuals with at least one A (adenine) allele of the rs75985579 (IFI16) are more than twice as likely to have periodontitis, while individuals with the G (guanine) allele of rs76457189 (AIM2) are less likely to be diagnosed with periodontitis, providing a negative association with periodontitis.

Assessing the implementation of a multi-component hypertension program in a Guatemalan under-resourced dynamic context: An application of the RE-AIM/PRISM extension for sustainability and health equity.

Background: The COVID-19 pandemic necessitated rapid changes in the delivery of care across public primary care settings in rural Guatemala in 2020. In response, a hypertension program implemented within the public primary care system required multiple adaptations, providing an illustrative example of dynamic implementation amidst changing context in an under-resourced setting. This study describes the evolvability of an evidence-based intervention (EBI; protocol-based hypertension treatment) and one of its main implementation strategies (team-based collaborative care) during the COVID-19 pandemic and discusses implications for health equity and sustainability. Methods: This convergent mixed methods analysis assessed implementation across five Ministry of Health districts during the initial phase of the pandemic. Qualitative and quantitative data were collected, analyzed, and integrated, informed by the RE-AIM (Reach, Effectiveness, Adoption, Implementation Maintenance) Framework's extension for sustainability, and its contextual enhancement, PRISM (Pragmatic, Robust, Implementation and Sustainability Model). For RE-AIM, we focused on the "Implementation" domain, operationalizing it qualitatively as continued delivery and adaptations to the EBI and implementation strategy, and quantitatively as the extent of delivery over time. We conducted 18 in-depth interviews with health providers / administrators (n=8) and study staff (n=10) and performed a matrix-based thematic-analysis. Qualitative results informed the selection of quantitative implementation summarized as behavior over time graphs. Quantitative implementation data and illustrative quotes are presented as joint displays. Results: In relation to implementation, several organic adaptations hindered delivery, threatened sustainability, and may have exacerbated health inequities. Planned adaptations enhanced program delivery and may have supported improved equity and sustainability. Salient PRISM factors that influenced implementation included "Organizational perspective of the EBI", "Fit" and "Implementation and sustainability infrastructure". Facilitators to continued delivery included the perception that the EBI is beneficial, program champions, and healthcare team organization. Barriers included the perception that the EBI is complicated, competition with other primary care activities, and temporary suspension of services due to COVID-19. Conclusions: Multi-level contextual changes led to numerous adaptations of the EBI and implementation strategy. Systems thinking approaches may shed light on how a program's sustainability and its equitable delivery are influenced by adaptations over time in response to dynamic, multi-level contextual factors. Trial registration: NCT03504124.

The development of a physical therapy service to treat urinary incontinence: Results of a RE-AIM evaluation.

Background: A conservative physiotherapy service development addressed to treat urinary incontinence for older women was studied using the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework. Design: We conducted a pragmatic case study design based on RE-AIM. Settings/participants: Included women ≥ 60 years of age, with self-reported UI symptoms. Results: A total of 34 older women were enrolled in the service with a mean age of 61.53 years. There was a significant improvement in the strength of the pelvic floor muscles, power, endurance, and fast contraction capacity after the intervention, however, it was observed a high dropout rate. Program implementation was supported by Physical Therapy teams who engaged in care coordination. The program has been maintained for over 4 years. Conclusion: Our findings demonstrate that UI patients would benefit from physiotherapy treatment and that this intervention is feasible. This RE-AIM evaluation provides lessons learned and strategies for future adoption, implementation, and maintenance of a Physical Therapy pelvic service.

AIM2 inflammasome activation may mediate high mobility group box 1 release in murine allergic rhinitis / Ativação do inflamassoma AIM2 pode mediar a liberação da proteína do grupo Box-1 de alta mobilidade no modelo murino de rinite alérgica

Abstract Introduction: High mobility group box 1 protein participates in the pathogenesis of allergic rhinitis. Activation of the inflammasome can mediate the release of high mobility group box 1. The role of the absent in melanoma 2 inflammasome in allergic rhinitis remains unclear. Objective: This study aimed to investigate the function of absent in melanoma 2 inflammasome in murine allergic rhinitis and the interaction between high mobility group box 1 and the absent in melanoma 2 inflammasome. Methods: A murine allergic rhinitis model was established using twenty Balb/c mice. Expression of the components of the absent in melanoma 2 inflammasome: absent in melanoma 2, apoptosis-associated speck-like protein containing a CARD (Asc), caspase-1 p20, and additional nod-like receptor family pyrin domain containing 3 (Nlrp3) were detected by western blotting during allergic rhinitis. Alterations of absent in melanoma 2, caspase-1, and high mobility group box 1 after ovalbumin challenge were demonstrated by immunohistochemistry. TdT-mediated dUTP Nick end labeling, TUNEL assay, and cleavage of caspase-3 and PARP-1 were used for the observation of pyroptosis. Results: Eosinophilia and goblet cell infiltration were observed in the nasal mucosa of mice in the allergic rhinitis group. Absent in melanoma 2, Asc, and caspase-1 p20 increased after ovalbumin exposure while Nlrp3 did not. High mobility group box 1 was released in the nasal mucosa of allergic rhinitis mice. TUNEL-positive cells increased in the epithelium and laminae propria, whereas cleavage of caspase-3 and PARP-1 was not observed. Conclusions: The absent in melanoma 2 inflammasome was activated and pyroptosis may occur in the nasal mucosa after ovalbumin treatment. These may contribute to the translocation of high mobility group box 1 and the development of allergic rhinitis.

Resumo Introdução: A proteína do grupo Box-1 de alta mobilidade participa da patogênese da rinite alérgica. A ativação do inflamassoma pode mediar a liberação de proteína do grupo Box-1 de alta mobilidade. O papel do inflamassoma ausente no melanoma 2 na rinite alérgica permanece incerto. Objetivo: Investigar a função do inflamassoma ausente no melanoma 2 em um modelo murino de rinite alérgica e a interação entre a proteína do grupo Box-1 de alta mobilidade e o inflamassoma ausente no melanoma 2. Método: Um modelo murino de rinite alérgica foi estabelecido com 20 camundongos Balb/c. A expressão dos componentes do inflamassoma ausente no melanoma 2, da proteína speck-like associada à apoptose com CARD (Asc), da caspase-1 p20 e do domínio de pirina da família NLR adicional com 3 (Nlrp3) foi detectada por western blotting durante a rinite alérgica. Alterações de inflamassoma ausente no melanoma 2, na caspase-1 e na proteína do grupo Box-1 de alta mobilidade após o teste de provocação com ovalbumina foram demonstradas por imuno-histoquímica. O ensaio dUTP Nick-End Labeling mediado por TdT, TUNEL e clivagem de caspase-3 e PARP-1 foram usados para a observação de piroptose. Resultados: Eosinofilia e infiltração de células caliciformes foram observadas na mucosa nasal de camundongos do grupo rinite alérgica. Inflamassoma ausente no melanoma 2, Asc e caspase-1 p20 aumentou após a exposição à ovalbumina, enquanto Nlrp3 não aumentou. A proteína do grupo Box-1 de alta mobilidade foi liberada na mucosa nasal de camundongos com rinite alérgica. As células TUNEL-positivas aumentaram no epitélio e na lâmina própria, enquanto a clivagem da caspase-3 e a PARP-1 não foram observadas. Conclusão: O inflamassoma ausente no melanoma 2 foi ativado e pode ocorrer piroptose na mucosa nasal após o tratamento com ovalbumina. Esses fatores podem contribuir para a translocação de proteína do grupo Box-1 de alta mobilidade e o desenvolvimento de rinite alérgica.

Time-dependent contraction of the SARS-CoV-2-specific T-cell responses in convalescent individuals.

Background: Adaptive immunity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is decisive for disease control. Delayed activation of T cells is associated with a worse outcome in coronavirus disease 2019 (COVID-19). Although convalescent individuals exhibit solid T-cell immunity, to date, long-term immunity to SARS-CoV-2 is still under investigation. Objectives: We aimed to characterize the specific T-cell response on the basis of the in vitro recall of IFN-γ-producing cells to in silico-predicted peptides in samples from SARS-CoV-2 convalescent individuals. Methods: The sequence of the SARS-CoV-2 genome was screened, leading to the identification of specific and promiscuous peptides predicted to be recognized by CD4+ and CD8+ T cells. Next, we performed an in vitro recall of specific T cells from PBMC samples from the participants. The results were analyzed according to clinical features of the cohort and HLA diversity. Results: Our results indicated heterogeneous T-cell responsiveness among the participants. Compared with patients who exhibited mild symptoms, hospitalized patients had a significantly higher magnitude of response. In addition, male and older patients showed a lower number of IFN-γ-producing cells. Analysis of samples collected after 180 days revealed a reduction in the number of specific circulating IFN-γ-producing T cells, suggesting decreased immunity against viral peptides. Conclusion: Our data are evidence that in silico-predicted peptides are highly recognized by T cells from convalescent individuals, suggesting a possible application for vaccine design. However, the number of specific T cells decreases 180 days after infection, which might be associated with reduced protection against reinfection over time.

AIM2 as a putative target in acute kidney graft rejection.

Acute rejection (AR) is a process triggered via the recognition of grafted organ-derived antigens by the immune system, which could present as a life-threatening condition. In the context of a kidney transplant, despite improvement with immunosuppressive therapies, AR maintains a significant incidence of 10%, and currently available drugs generally act in similar and canonical pathways of lymphocyte activation. This prompted the research for different approaches to identify potential novel targets that could improve therapeutic interventions. Here, we conducted a transcriptome analysis comparing groups of acute rejection (including T cell-mediated rejection and antibody-mediated rejection) to stable grafts that included differentially expressed genes, transcription factor and kinase enrichment, and Gene Set Enrichment Analysis. These analyses revealed inflammasome enhancement in rejected grafts and AIM2 as a potential component linked to acute rejection, presenting a positive correlation to T-cell activation and a negative correlation to oxidative phosphorylation metabolism. Also, the AIM2 expression showed a global accuracy in discerning acute rejection grafts (area under the curve (AUC) = 0.755 and 0.894, p < 0.0001), and meta-analysis comprising different studies indicated a considerable enhancement of AIM2 in rejection (standardized mean difference (SMD) = 1.45, [CI 95%, 1.18 to 1.71]), especially for T cell-mediated rejection (TCMR) (SMD = 2.01, [CI 95%, 1.58 to 2.45]). These findings could guide future studies of AIM2 as either an adjuvant target for immunosuppression or a potential biomarker for acute rejection and graft survival.

Long-term Mammography Utilization after an Initial Randomized Intervention Period by all Underserved Chilean Women in the Clinics.

Chile has one of the highest rates of breast cancer in Latin America. Mammography rates among women, especially those of low socioeconomic status (SES), are thought to contribute to high breast cancer morbidity and mortality. A successful randomized controlled trial among women aged 50 to 70 in a low-SES primary care clinic in Chile led to a significant increase in mammography screening rates in a two-year intervention trial. This study assesses the sustainability of the intervention after ten years and identifies factors that might have been associated with a long-term effect using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. The mammography rates among women aged 50 to 70 in the low-SES intervention clinic were compared to two populations of women aged 50 to 70 from middle-SES clinics and to national data. Qualitative data were used to answer questions of adoption, implementation, and maintenance, while quantitative data assessed the reach and effectiveness. After ten years, low-SES women at the intervention clinic maintained significantly higher mammography screening rates vs. middle-SES women at the comparison clinics (36.2% vs. 30.1% and 19.4% p < 0.0001). Women of a low SES at the intervention clinic also had significantly higher screening rates compared to women of a low SES at a national level (44.2% vs. 34.2% p < 0.0001). RE-AIM factors contributed to understanding the long-term difference in rates. Mailed contact, outreach interventions, and the integration of health promoters as part of the Community Advisory Board were important factors associated with the effects observed. This study provides information on factors that could contribute to reducing the social gap on breast cancer screening.

Immunization With Lipopolysaccharide-Activated Dendritic Cells Generates a Specific CD8+ T Cell Response That Confers Partial Protection Against Infection With Trypanosoma cruzi.

Lipopolysaccharide (LPS) induces the activation of dendritic cells (DCs) throughout the engagement of toll-like receptor 4. LPS-activated DCs show increased capacity to process and present pathogen-derived antigens to activate naïve T cells. DCs-based vaccines have been successfully used to treat some cancer types, and lately transferred to the field of infectious diseases, in particular against HIV. However, there is no vaccine or DC therapy for any parasitic disease that is currently available. The immune response against Trypanosoma cruzi substantially relies on T cells, and both CD4+ and CD8+ T lymphocytes are required to control parasite growth. Here, we develop a vaccination strategy based on DCs derived from bone marrow, activated with LPS and loaded with TsKb20, an immunodominant epitope of the trans-sialidase family of proteins. We extensively characterized the CD8+ T cell response generated after immunization and compared three different readouts: a tetramer staining, ELISpot and Activation-Induced Marker (AIM) assays. To our knowledge, this work shows for the first time a proper set of T cell markers to evaluate specific CD8+ T cell responses in mice. We also show that our immunization scheme confers protection against T. cruzi, augmenting survival and reducing parasite burden in female but not male mice. We conclude that the immunization with LPS-activated DCs has the potential to prime significant CD8+ T cell responses in C57BL/6 mice independently of the sex, but this response will only be effective in female, possibly due to mice sexual dimorphisms in the response generated against T. cruzi.

AIM2-inflammasome role in systemic lupus erythematous and rheumatoid arthritis.

The inflammasome AIM2 regulates multiple aspects of innate immune functions and serves as a critical mediator of inflammatory responses. AIM2 inflammasome activation leads to the production of pro-inflammatory cytokines, IL-1ß and IL-18 and participates triggering a pyroptosis response needed to counteract excessive cell proliferation. In addition, AIM2 expression and activation is wide regulated since alteration in its activity may derived in pathological consequences. Consequently, deregulated AIM2 activation contributes to the pathogenic processes of various inflammatory diseases. In this review, we will discuss the activation and function of AIM2 inflammasome, as well as its contribution in rheumatoid arthritis and systemic lupus erythematous pathology. Finally, we highlight the participation of the AIM2-inflammasome at the level of joint in rheumatoid arthritis and at kidney in systemic lupus erythematous. The development of therapeutic strategies based on modulation of AIM2-inflammasome activity should have a tissue-specific focus.

Involvement of Inflammasome Components in Kidney Disease.

Inflammasomes are multiprotein complexes with an important role in the innate immune response. Canonical activation of inflammasomes results in caspase-1 activation and maturation of cytokines interleukin-1ß and -18. These cytokines can elicit their effects through receptor activation, both locally within a certain tissue and systemically. Animal models of kidney diseases have shown inflammasome involvement in inflammation, pyroptosis and fibrosis. In particular, the inflammasome component nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) and related canonical mechanisms have been investigated. However, it has become increasingly clear that other inflammasome components are also of importance in kidney disease. Moreover, it is becoming obvious that the range of molecular interaction partners of inflammasome components in kidney diseases is wide. This review provides insights into these current areas of research, with special emphasis on the interaction of inflammasome components and redox signalling, endoplasmic reticulum stress, and mitochondrial function. We present our findings separately for acute kidney injury and chronic kidney disease. As we strictly divided the results into preclinical and clinical data, this review enables comparison of results from those complementary research specialities. However, it also reveals that knowledge gaps exist, especially in clinical acute kidney injury inflammasome research. Furthermore, patient comorbidities and treatments seem important drivers of inflammasome component alterations in human kidney disease.

AIM2 inflammasome activation may mediate high mobility group box 1 release in murine allergic rhinitis.

INTRODUCTION: High mobility group box 1 protein participates in the pathogenesis of allergic rhinitis. Activation of the inflammasome can mediate the release of high mobility group box 1. The role of the absent in melanoma 2 inflammasome in allergic rhinitis remains unclear. OBJECTIVE: This study aimed to investigate the function of absent in melanoma 2 inflammasome in murine allergic rhinitis and the interaction between high mobility group box 1 and the absent in melanoma 2 inflammasome. METHODS: A murine allergic rhinitis model was established using twenty Balb/c mice. Expression of the components of the absent in melanoma 2 inflammasome: absent in melanoma 2, apoptosis-associated speck-like protein containing a CARD (Asc), caspase-1 p20, and additional nod-like receptor family pyrin domain containing 3 (Nlrp3) were detected by western blotting during allergic rhinitis. Alterations of absent in melanoma 2, caspase-1, and high mobility group box 1 after ovalbumin challenge were demonstrated by immunohistochemistry. TdT-mediated dUTP Nick end labeling, TUNEL assay, and cleavage of caspase-3 and PARP-1 were used for the observation of pyroptosis. RESULTS: Eosinophilia and goblet cell infiltration were observed in the nasal mucosa of mice in the allergic rhinitis group. Absent in melanoma 2, Asc, and caspase-1 p20 increased after ovalbumin exposure while Nlrp3 did not. High mobility group box 1 was released in the nasal mucosa of allergic rhinitis mice. TUNEL-positive cells increased in the epithelium and laminae propria, whereas cleavage of caspase-3 and PARP-1 was not observed. CONCLUSIONS: The absent in melanoma 2 inflammasome was activated and pyroptosis may occur in the nasal mucosa after ovalbumin treatment. These may contribute to the translocation of high mobility group box 1 and the development of allergic rhinitis.

Inclusión de la práctica colaborativa interprofesional para la promoción y prevención de la salud bucal / Inclusion of interprofessional collaborative practice for the promotion and prevention of oral health / Inclusão da prática interprofissional colaborativa para a promoção e prevenção da saúde bucal

Resumen Las actividades de promoción y prevención en Salud son relevantes en la Atención Primaria; no obstante, las relacionadas con el Programa de Salud Oral, en Chile, aparecen asociadas a los programas preventivos y no formando parte de ellos, situación que también ocurre en otros países. La presente revisión tiene como objetivos evidenciar las actuales políticas y lineamientos internacionales que indican que se debe propender a una Práctica Colaborativa Interprofesional para una mejor calidad en la atención; y proponer un trabajo interprofesional donde las acciones de promoción y prevención en Salud Bucal se incluyan en los programas preventivos existentes. La Práctica Colaborativa Interprofesional ocurre cuando los miembros del equipo de salud se organizan, planifican, gestionan y proporcionan servicios integrales de salud, evitando la fragmentación de los cuidados. Esto se logra estructurando las competencias comunes, colaborativas y específicas. El trabajo interdependiente permite complementar conocimientos y habilidades que contribuyen a cumplir con las políticas de Calidad de la Atención y Triple Meta en salud. De modo que, se proponen estrategias de trabajo en promoción y prevención de Salud Bucal a incorporar y ejecutar en los diversos programas preventivos ya existentes a lo largo del ciclo vital. En conclusión, es necesario un cambio de paradigma en la atención bucodental donde el foco ya no esté en el programa sino en el individuo, familia y comunidad para lograr una salud integral. Resulta relevante compartir experiencias de atención interprofesional y a incorporar la Educación Interprofesional y Practica Colaborativa en el proceso formativo de las futuras generaciones.

Abstract Health prevention and promotion actions are relevant in primary care; nevertheless, those related to the Oral Health Program in Chile are associated with preventive programs and are not part of them, which occurs in other countries as well. The objectives of this review are to display the current international policies and guidelines that indicate that an Interprofessional Collaborative Practice should be promoted for a better quality of care as well as to propose interprofessional work including promotion and prevention actions in Oral Health in the existing preventive programs. Interprofessional Collaborative Practice occurs when members of the health team organize, plan, manage and provide integral health services, avoiding fragmentation of care. This is achieved by structuring common, collaborative, and specific competencies. Interdependent work allows complementing knowledge and skills that contribute to comply with the policies of Quality of Care and Triple Aim in health. Therefore, work strategies in oral health promotion and prevention are proposed to be incorporated and implemented in the various preventive programs already in place throughout the life cycle. In conclusion, there is a need for a paradigm shift in oral health care, where the focus is no longer on the program but on the individual, family, and community to achieve comprehensive health. Finally, it becomes relevant to share experiences of interprofessional care, and incorporating Interprofessional Education and Collaborative Practice in the formative process of future generations.

Resumo As atividades de promoção e prevenção da saúde são relevantes na Atenção Básica; no entanto, aqueles relacionados ao Programa de Saúde Bucal no Chile aparecem associados aos programas preventivos e não fazem parte deles, situação que também ocorre em outros países. A presente revisão visa demonstrar as atuais políticas e diretrizes internacionais que indicam que uma Prática Interprofissional Colaborativa deve ser promovida para uma melhor qualidade de atendimento; e propor um trabalho interprofissional onde as ações de promoção e prevenção em Saúde Bucal estejam incluídas nos programas preventivos existentes. A Prática Colaborativa Interprofissional ocorre quando os membros da equipe de saúde organizam, planejam, gerenciam e prestam serviços de saúde integrais, evitando a fragmentação do cuidado. Isso é conseguido através da estruturação de competências comuns, colaborativas e específicas. O trabalho interdependente permite complementar conhecimentos e competências que contribuem para o cumprimento das políticas de Qualidade da Assistência e Triplo Objetivo em saúde. Assim, são propostas estratégias de trabalho na promoção e prevenção da Saúde Bucal a serem incorporadas e executadas nos diversos programas preventivos já existentes ao longo do ciclo vital. Conclui-se que é necessária uma mudança de paradigma na higiene bucal, onde o foco não seja mais o programa, mas sim o indivíduo, a família e a comunidade para o alcance da saúde integral. É relevante compartilhar experiências de cuidado interprofissional e incorporar a Educação Interprofissional e a Prática Colaborativa no processo de formação das futuras gerações.