De Salud Research Articles

Recombinant Surface Immunogenic Protein from S. agalactiaeand hemocyanin from Fisurella latimarginatapromote cross-presentation dependence on the TLR-4 signaling

Abstract Improved vaccine adjuvants are needed to address infectious diseases, cancer, and future pandemics. Toll-like receptors (TLRs) have been researched as targets of vaccine adjuvants because they modulate the innate immune system and activate adaptive immunity. TLR-based adjuvants induce cross-presentation of exogenous antigens to CD8 T lymphocytes. TLR4 signaling recruits the adapters myeloid differentiation marker 88 (MyD88), which mediates the recycling of endoplasmic reticulum fusion to the phagosome as well as the TIR-domain-containing adapter-inducing interferon-β (TRIF), which is essential for translocation from the endosome to the cytosol. Given the role of TLR4 agonists, most studies have used ligands based on lipopolysaccharides, but these have side effects (especially fever). Here we propose using TLR4 protein-based agonists (TLR-4-PBA), which have multiple advantages as adjuvants: They are naturally biocompatible and biodegradable substances that induce minimal reactogenicity and toxicity. We studied mollusk hemocyanin from Fissurella latimarginata(FLH) and the recombinant surface immunogenic protein from Streptococcus agalactiae(rSIP). These two proteins differ significantly in their structure, and we show Th1 immunomodulatory properties. Using mouse bone marrow-derived dendritic cells pulsed with ovoalbumin (OVA), we then showed that rSIP and FLH promote cross-presentation in OT-I CD8+ T lymphocytes. This effect depends on TLR4 and the recruitment of MyD88 and TRIF. Studies are in progress to evaluate IRF3 and NF-κ B activation.Our results illustrate how these TLR-4-PBAs could act as a clinically useful vaccine adjuvant for innate immunity and Th1 adaptive immune response. FONDECYT 1201600 (MIB); FONDEF ID21I10370 (AEV), Instituto de Salud Pública de Chile Funding (AEV, DD-D); ANID/PhD Nacional program 21210946 (MLS) and 21200880 (DD-D); FONDAP 15130011 (MT, SL).

Effect of walnut consumption on neuropsychological development in healthy adolescents: a multi-school randomised controlled trial

Omega-3 fatty acids are critical for neuropsychological functioning. Adolescence is increasingly believed to entail brain vulnerability to dietary intake. The potential benefit on adolescent neurodevelopment of consuming walnuts, a source of omega-3 alpha-linolenic acid (ALA), remains unclear. We conducted a 6-month multi-school-based randomised controlled nutrition intervention trial to assess whether walnut consumption has beneficial effects on the neuropsychological and behavioural development of adolescents. The study took place between 04/01/2016 and 06/30/2017 in twelve different high schools in Barcelona, Spain (ClinicalTrials.gov Identifier: NCT02590848). A total of 771 healthy teenagers aged 11-16 years were randomised into two equal groups (intervention or control). The intervention group received 30g/day of raw walnut kernels to be incorporated into their diet for 6 months. Multiple primary endpoints concerning neuropsychological (working memory, attention, fluid intelligence, and executive function) and behavioural (socio-emotional and attention deficit hyperactivity disorder [ADHD] symptoms) development were assessed at baseline and after intervention. Red blood cell (RBC) ALA status was determined at baseline and 6 months as a measure of compliance. Main analyses were based on intention-to-treat using a linear mixed-effects model. A per-protocol effect of the intervention was analysed using inverse-probability weighting to account for post-randomisation prognostic factors (including adherence) using generalised estimating equations. In intention-to-treat analyses, at 6 months there were no statistically significant changes between the intervention and control groups for all primary endpoints. RBC ALA (%) significantly increased only in the intervention group, coefficient=0.04 (95% Confidence Interval (CI)=0.03, 0.06; p<0.0001). The per-protocol (adherence-adjusted) effect on improvement in attention score (hit reaction time variability) was-11.26ms (95% CI=-19.92,-2.60; p=0.011) for the intervention group as compared to the control group, improvement in fluid intelligence score was 1.78 (95% CI=0.90, 2.67; p<0.0001), and reduction of ADHD symptom score was-2.18 (95% CI=-3.70,-0.67; p=0.0050). Our study suggested that being prescribed eating walnuts for 6 months did not improve the neuropsychological function of healthy adolescents. However, improved sustained attention, fluid intelligence, and ADHD symptoms were observed in participants who better complied with the walnut intervention. This study provides a foundation for further clinical and epidemiological research on the effect of walnuts and ALA on neurodevelopment in adolescents. This study was supported by Instituto de Salud Carlos III through the projects 'CP14/00108, PI16/00261, PI21/00266' (co-funded by European Union Regional Development Fund 'A way to make Europe'). The California Walnut Commission (CWC) has given support by supplying the walnuts for free for the Walnuts Smart Snack Dietary Intervention Trial.

Strategies on critical levels and nodes to improve self-management in people with cardiovascular risk factors in COVID-19 pandemic conditions

Chile faced the Sars-Cov-2 pandemic, which coexisted with food-nutritional problems related to non-communicable diseases (NCDs). Due to this context, individuals with chronic conditions had less chance to receive medical attention due to the restructuring of the public health system. The present study aimed to identify strategies that integrate the individual, community, and structural levels to improve health control in habitual and critical situations. The study included individuals attending the Cardiovascular Health Program (Programa de Salud Cardiovascular) at the primary care level in the capital city of Santiago during the COVID-19 pandemic. Nine hundred forty individuals attending the Cardiovascular Health Program answered a 40-question telephonic interview. With the results of the analysis (convergence analyses, the complement of quantitative and qualitative results), we performed a seminar with key stakeholders from the Ministry of Health and the primary care level. Our study describes integrative strategies that include the individual level, the community level, and structural aspects. These strategies may improve healthcare management among people with NCDs and could be helpful to face interruptions of health benefits and improve health control in everyday and critical situations. The strategies include three levels: 1) Cardiovascular Health Program redesign; 2) facing health attendance discontinuities, and 3) structural measures. It is necessary to re-evaluate primary care policies in light of these proposed strategies for sharing responsibility and empowering users about their abilities.

Patients who develop insulin resistance 4-months post-COVID-19 exhibited higher NETosis and miR-21-5p expression than COVID-19 patients without metabolic alterations.

Abstract Post COVID-19 has been associated with alterations in the glucidic metabolism and the presence of metabolic-related microRNAs (miRNAs). Since neutrophils response depends on glycolysis, it is unclear whether the formation of neutrophil extracellular traps (NETosis) is also affected in post COVID-19 patients that developed insulin resistance (IR) post infection. In addition, miR-21-5p has been described as a direct gene regulator of the innate immune response against COVID-19 and the presence of IR. In this study, we evaluated NETosis at 4-months post-COVID-19 and its association with the development of IR and the expression of circulating miR-21-5p. Sixty post-COVID-19 patients were recruited from Víctor-Rios-Ruiz Hospital, and post COVID-19 was evaluated 4-months after acute phase. Serum samples were used to determine biochemical parameters. NETosis was measured in patients at basal condition and in response to TLR agonists using flow cytometry. miR-21-5p expression was measured with RT-qPCR. From our cohort, 19 patients were excluded because of they had IR or type 2 diabetes mellitus before COVID-19, 25 patients developed new IR and 16 remained without glucidic alteration. Our analysis showed that COVID-19 patients with IR-Post-COVID-19 had a significant increment of NETosis in basal condition, reducing the capacity to respond efficiently to TRL3/7/8 agonists. We also found a significant increment of miR-21-5p expression in IR-Post-COVID-19 patients and a significant and positive correlation between miR-21-5p and vital NETosis. These results demonstrated that patients who developed IR post-COVID-19 exhibited higher basal NETosis and higher miR-21-5p expression in comparison with patients without alterations. Supported by grants from PROYECTO COVID1005, ACT210085, Fondecyt Regular 1211480, Instituto de Salud Carlos III (COV20/00110, CP20/00041), Programa de donaciones "estar preparados" UNESPA (Madrid, Spain), Fundación Francisco Soria Melguizo (Madrid, Spain).

Profile of serum biomarkers in seronegative NMOSD (S50.009)

Profile of serum biomarkers in seronegative NMOSD (S50.009)

Incidence of syndromes associated with Frontotemporal Lobar Degeneration (S19.004)

Incidence of syndromes associated with Frontotemporal Lobar Degeneration (S19.004)

Clinical characterisation of patients in the post-acute stage of anti-NMDA receptor encephalitis: a prospective cohort study and comparison with patients with schizophrenia spectrum disorders (S22.006)

Clinical characterisation of patients in the post-acute stage of anti-NMDA receptor encephalitis: a prospective cohort study and comparison with patients with schizophrenia spectrum disorders (S22.006)

Predicting MRI Changes in Patients with MS in the Absence of Acute Inflammation (P11-3.010)

Predicting MRI Changes in Patients with MS in the Absence of Acute Inflammation (P11-3.010)

Evobrutinib therapeutic response is associated with an increase in the number and maturation of peripheral and central classical dendritic cells (P7-3.005)

<h3>Objective:</h3> To assess the impact of evobrutinib on classical dendritic cells (cDCs) in the MOG_35–55-induced chronic-progressive experimental autoimmune encephalomyelitis (EAE) Multiple sclerosis (MS) model (with limited B cell contribution). <h3>Background:</h3> Evobrutinib is an oral, highly selective covalent Bruton’s tyrosine kinase (BTK) inhibitor with promising results in a Phase II trial for relapsing MS. Lately, the role of BTK in myeloid cell activity, including cDCs, has been gaining importance in MS pathogenesis. <h3>Design/Methods:</h3> Female EAE mice received individualized daily oral treatment of vehicle (EAE-Veh) or evobrutinib (EAE-Evo) for 4 days from the day of disease onset. EAE was scored clinically each day and flow cytometry analyses of spleens and spinal cords were performed. EAE-Evo mice with a clinical course indistinguishable from that of EAE-Veh were classified as non-responders (Evo-NR), whereas those with less severe disease were considered responders (Evo-R). <h3>Results:</h3> The therapeutic response in Evo-R was associated with an increase in MHC-II⁺ cDC (mature cDCs) in the spleen. Evobrutinib shifted the correlation between CD69⁺ T cells/cDCs from positive to inverse. However, Evo-NR mice showed myeloid content similar to EAE-Veh mice and Evo-R mice exhibited a lower myeloid cell infiltrate in the spinal cord, albeit enriched in mature cDCs. Evobrutinib induced specific modifications in the immunological synapse components in cDCs. Whereas both Evo-R and Evo-NR showed a decrease in MHC-II in splenic cDCs, only Evo-R exhibited a decrease in CD80. In contrast, spinal cord cDCs showed decreased CD80 with no modification of MHC-II brightness. <h3>Conclusions:</h3> In the EAE model, evobrutinib therapeutic response shows a clear relationship with the enrichment of mature cDCs at both the peripheral and central levels, with a decrease in activated T cell presence. The interpretation of the immunological alteration of cDCs by evobrutinib will be further investigated using functional <i>ex vivo</i> assays. <b>Disclosure:</b> The institution of Dr. Clemente has received research support from EMD Serono Research &amp; Development Institute, Inc.. The institution of Dr. Clemente has received research support from Bristol Myers Squibb. The institution of Dr. Clemente has received research support from Instituto de Salud Carlos III. Dr. Clemente has received personal compensation in the range of $500-$4,999 for serving as a Reviewer of Grants with Spanish National Investigation Agency. Dr. Serrano Regal has nothing to disclose. Dr. Calahorra has nothing to disclose. Miss Alonso García has nothing to disclose. Ursula Boschert has nothing to disclose. Philipp Haselmayer has received personal compensation for serving as an employee of Merck Healthcare KGaA. Dr. Ortega has nothing to disclose. Miss Díaz has nothing to disclose. Mrs. Camacho Toledano has nothing to disclose. Mrs. Arocha has nothing to disclose.

Effect of viral storm in patients admitted to intensive care units with severe COVID-19 in Spain: a multicentre, prospective, cohort study

The contribution of the virus to the pathogenesis of severe COVID-19 is still unclear. We aimed to evaluate associations between viral RNA load in plasma and host response, complications, and deaths in critically ill patients with COVID-19. We did a prospective cohort study across 23 hospitals in Spain. We included patients aged 18 years or older with laboratory-confirmed SARS-CoV-2 infection who were admitted to an intensive care unit between March 16, 2020, and Feb 27, 2021. RNA of the SARS-CoV-2 nucleocapsid region 1 (N1) was quantified in plasma samples collected from patients in the first 48 h following admission, using digital PCR. Patients were grouped on the basis of N1 quantity: VIR-N1-Zero (<1 N1 copies per mL), VIR-N1-Low (1-2747 N1 copies per mL), and VIR-N1-Storm (>2747 N1 copies per mL). The primary outcome was all-cause death within 90 days after admission. We evaluated odds ratios (ORs) for the primary outcome between groups using a logistic regression analysis. 1068 patients met the inclusion criteria, of whom 117 had insufficient plasma samples and 115 had key information missing. 836 patients were included in the analysis, of whom 403 (48%) were in the VIR-N1-Low group, 283 (34%) were in the VIR-N1-Storm group, and 150 (18%) were in the VIR-N1-Zero group. Overall, patients in the VIR-N1-Storm group had the most severe disease: 266 (94%) of 283 patients received invasive mechanical ventilation (IMV), 116 (41%) developed acute kidney injury, 180 (65%) had secondary infections, and 148 (52%) died within 90 days. Patients in the VIR-N1-Zero group had the least severe disease: 81 (54%) of 150 received IMV, 34 (23%) developed acute kidney injury, 47 (32%) had secondary infections, and 26 (17%) died within 90 days (OR for death 0·30, 95% CI 0·16-0·55; p<0·0001, compared with the VIR-N1-Storm group). 106 (26%) of 403 patients in the VIR-N1-Low group died within 90 days (OR for death 0·39, 95% CI 0·26-0·57; p<0·0001, compared with the VIR-N1-Storm group). The presence of a so-called viral storm is associated with increased all-cause death in patients admitted to the intensive care unit with severe COVID-19. Preventing this viral storm could help to reduce poor outcomes. Viral storm could be an enrichment marker for treatment with antivirals or purification devices to remove viral components from the blood. Instituto de Salud Carlos III, Canadian Institutes of Health Research, Li Ka-Shing Foundation, Research Nova Scotia, and European Society of Clinical Microbiology and Infectious Diseases. For the Spanish translation of the abstract see Supplementary Materials section.

Clinical characterization and outcome of 47 patients with neurologic adverse events of immune-checkpoint inhibitors (P4-5.026)

<h3>Objective:</h3> To report the clinical spectrum, treatment, and outcome of a case series of neurologic iAEs. <h3>Background:</h3> Cancer treatment with immune checkpoint inhibitors (ICI) can associate with immune-related adverse events (iAEs) which can be life-threatening. <h3>Design/Methods:</h3> Retrospective assessment of patients with neurologic iAEs whose serum or CSF samples were studied in our laboratory (Jan2018–Sep2022). Clinical information was obtained through a structured questionnaire. Exclusion criteria were lack of clinical information and evidence of other causes of neurologic dysfunction. Treatment response was assessed within one month of symptom onset, and outcome at last follow-up visit. <h3>Results:</h3> 47 patients (29 males, 62%), median age 67 years (IQR60–74) were included. The most frequent tumors were lung cancer (28, 60%) and melanoma (9, 19%). 26 (55%) patients received anti-PD1, 13 (28%) PDL-1, and 8 (17%) both. Median time to neurologic iAEs was 15 weeks (IQR3–32). The initial presentations were: encephalopathy (30 patients, 64%), muscle weakness (9, 19%), ataxia (3, 6%), visual dysfunction (3, 6%), and constipation (2, 4%). Median mRS at nadir was 4 (3–5), and 7 (15%) patients required ICU. Abs were detected in 10 (21%; Ma2=3, Hu=2, GFAP=2, GABAbR=1, GAD65=1, AQP4=1). 42 (89%) were treated; all received steroids, 17 (36%) intravenous immunoglobulins, and 9 (21%) other immunosuppressants. Patients without early neurologic improvement (14, 30%) were more likely to be older, have lung cancer (p=0.01), and higher mRS at nadir (p=0.001) than those who improved. After a median follow-up of 107 days (45–356), mRS was 3 (0–6), and 26 (55%) patients had a poor outcome: 23 (49%) died (10 [21%] related to neurologic iAE) and the other 3 didn’t improve or worsened. Good outcome was associated with early neurologic improvement (p=0.001). <h3>Conclusions:</h3> In this case series with predominant CNS iAEs, half of the patients had poor clinical outcome, and in 20% the neurologic iAE was the cause of death. <b>Disclosure:</b> Elianet Fonseca has nothing to disclose. Mr. Cabrera Maqueda has nothing to disclose. Raquel Ruiz-Garcia has nothing to disclose. Dr. Naranjo Rondan has nothing to disclose. Dr. Blanco Morgado has nothing to disclose. Dr. Dalmau has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas Research Institute of America. Dr. Dalmau has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen Research &amp; Development . Dr. Dalmau has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Academy of Neurology. An immediate family member of Dr. Dalmau has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Dalmau has received research support from Sage Therapeutics. The institution of Dr. Dalmau has received research support from Edmond J.Safra Foundation . The institution of Dr. Dalmau has received research support from La Caixa Foundation. The institution of Dr. Dalmau has received research support from Spanish Ministry of Health (ISCIII). The institution of Dr. Dalmau has received research support from Euroimmun, Inc. Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care. Dr. Graus has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MedLink. Dr. Graus has received intellectual property interests from a discovery or technology relating to health care. The institution of Dr. Martinez-Hernandez has received research support from Instituto de Salud Carlos III. Dr. Martinez-Hernandez has received personal compensation in the range of $0-$499 for serving as a travel and speaking honoraria with Biogen. Dr. Martinez-Hernandez has received personal compensation in the range of $0-$499 for serving as a travel honoraria with UCB.

Baseline predictors of disability worsening among patients wth a Clinically Isolated Syndrome. (P5-3.015)

Baseline predictors of disability worsening among patients wth a Clinically Isolated Syndrome. (P5-3.015)

Impact of the 'reserved therapeutic space' nursing intervention on patient health outcomes: An intervention study in acute mental health units.

To evaluate the effectiveness of the 'reserved therapeutic space' intervention for improving the nurse-patient therapeutic relationship in acute mental health units in Spain. Multicentre intervention study with control group. The study will be carried out in 12 mental health units. The 'reserved therapeutic space' intervention to be tested has been co-designed and validated by both nurses and patients. The quality of the therapeutic relationship, the care received and perceived coercion among patients will be assessed. An estimated 131 patients per group are expected to participate. Funding was granted by the Instituto de Salud Carlos III. Co-financed by the European Union (European Regional Development Fund (ERDF) (PI21/00605))andCollege of Nurses of Barcelona(PR-487/2021). The proposal was approved by all the Research Ethics Committees of participating centres. This project will lead to changes in clinical practice, transforming the current models of organization and care management in mental health hospitalization units. No patient or public contribution.

State-level prevalence of anemia in women of reproductive age. Ensanut 2006, 2012 and 2018-19

Objective. To compare the prevalence of anemia and iron deficiency, at state level in non-pregnant women between 20 and 49 years of age from the Encuesta Nacional de Salud y Nutrición (Ensanut, in Spanish) 2006, 2012 and 2018-19. Materials and methods. The Ensanut 2006, 2012 and 2018-19 have a probabilistic design. Hb in capillary blood was measured by HemoCue Hb201 and ferritin by venous sample. Anemia was diagnosed with Hb&lt;120g/L and iron deficiency with Ferritin&lt;15ng/mL. Results. At the national level, anemia increased 6.1 (p&lt;0.05) percentage points (pp) from 2006 to 2018-19. Baja California Norte, Campeche, Colima, Chiapas, Quintana Roo, Sinaloa and Sonora, went from low prevalence (5 to 19.9%) to moderate (20 to 39.9%); in Yucatán and Tamaulipas it went from low to severe (&gt;40). In Guanajuato, State of Mexico and Querétaro it was reduced from 2006 to 2018-19 (p&lt;0.05). Conclusions. Anemia continues to be a public health problem that requires actions at the state level, considering level of wellbeing index, food programs and affiliation to medical Services insurance.

Anaemia in adolescent women: A priority for the nutrition agenda in Mexico. A comparison of data from the ENSANUT 2012 and 2018–2019 surveys

The risk of anaemia in adolescence increases due to accelerated growth. This study aims to: (1) estimate the prevalence of anaemia in 2012 and 2018-2019 (Encuesta Nacional de Salud y Nutricion - ENSANUT [n = 5841 in 2012 and n = 2380 in 2018-2019]) in non-pregnant, Mexican adolescent women aged 12-19 years, and the changes in prevalence over this period according to sociodemographic, health and nutrition characteristics; (2) estimate the associations between anaemia and sociodemographic, health and nutrition characteristics in each year and overall, in non-pregnant Mexican adolescent women. Anaemia was defined as capillary haemoglobin <12 g/dL. The distribution of characteristics and their changes between 2012 and 2018-2019 were described. The covariate-adjusted prevalence of anaemia in 2012 and 2018-2019 and the changes over that period were estimated from a multiple log-binomial regression model and the factors associated with anaemia were assessed in each survey year and in both years combined. The prevalence of anaemia was 7.7% in 2012 and 13.1% in 2018-2019 (69% increase, Prevalence Ratio: PR = 1.69; 95%CI: 1.35, 2.13). The covariate-adjusted prevalence of anaemia increased from 6.9% to 10.5% in the overall population (PR = 1.53, 95%CI: 1.19, 1.96), and increased considerably in the age group 12-14 years (PR = 1.94, 95%CI: 1.36, 2.75), and in the northern region (PR = 3.68, 95%CI: 2.55, 5.32). Those receiving iron supplements or school breakfasts did not register a significant increase. A higher household wellbeing status and older age were associated with a lower prevalence of anaemia. Anaemia in non-pregnant adolescent women continues to be a public health problem. To improve the development and health of adolescent women in Mexico and to pave the way to a healthy pregnancy for the next generation, the causes of anaemia should be identified.

Etiology of acute febrile illness in the peruvian amazon as determined by modular formatted quantitative PCR: a protocol for RIVERA, a health facility-based case-control study

BackgroundThe study of the etiology of acute febrile illness (AFI) has historically been designed as a prevalence of pathogens detected from a case series. This strategy has an inherent unrealistic assumption that all pathogen detection allows for causal attribution, despite known asymptomatic carriage of the principal causes of acute febrile illness in most low- and middle-income countries (LMICs). We designed a semi-quantitative PCR in a modular format to detect bloodborne agents of acute febrile illness that encompassed common etiologies of AFI in the region, etiologies of recent epidemics, etiologies that require an immediate public health response and additional pathogens of unknown endemicity. We then designed a study that would delineate background levels of transmission in the community in the absence of symptoms to provide corrected estimates of attribution for the principal determinants of AFI.MethodsA case-control study of acute febrile illness in patients ten years or older seeking health care in Iquitos, Loreto, Peru, was planned. Upon enrollment, we will obtain blood, saliva, and mid-turbinate nasal swabs at enrollment with a follow-up visit on day 21–28 following enrollment to attain vital status and convalescent saliva and blood samples, as well as a questionnaire including clinical, socio-demographic, occupational, travel, and animal contact information for each participant. Whole blood samples are to be simultaneously tested for 32 pathogens using TaqMan array cards. Mid-turbinate samples will be tested for SARS-CoV-2, Influenza A and Influenza B. Conditional logistic regression models will be fitted treating case/control status as the outcome and with pathogen-specific sample positivity as predictors to attain estimates of attributable pathogen fractions for AFI.DiscussionThe modular PCR platforms will allow for reporting of all primary results of respiratory samples within 72 h and blood samples within one week, allowing for results to influence local medical practice and enable timely public health responses. The inclusion of controls will allow for a more accurate estimate of the importance of specific prevalent pathogens as a cause of acute illness.Study RegistrationProject 1791, Registro de Proyectos de Investigación en Salud Pública (PRISA), Instituto Nacional de Salud, Perú.

Toll-like receptor agonists enhance HIV-specific T cell response mediated by plasmacytoid dendritic cells in diverse HIV-1 disease progression phenotypes

Plasmacytoid dendritic cells (pDCs) sense viral and bacterial products through Toll-like receptor (TLR)-7 and-9 and translate this sensing into Interferon-α (IFN-α) production and T-cell activation. The understanding of the mechanisms involved in pDCs stimulation may contribute to HIV-cure immunotherapeutic strategies. The objective of the present study was to characterize the immunomodulatory effects of TLR agonist stimulations in several HIV-1 disease progression phenotypes and in non HIV-1 infected donors. pDCs, CD4 and CD8 T-cells were isolated from 450ml of whole blood from non HIV-1 infected donors, immune responders (IR), immune non responders (INR), viremic (VIR) and elite controller (EC) participants. pDCs were stimulated overnight with AT-2, CpG-A, CpG-C and GS-9620 or no stimuli. After that, pDCs were co-cultured with autologous CD4 or CD8 T-cells and with/without HIV-1 (Gag peptide pool) or SEB (Staphylococcal Enterotoxin B). Cytokine array, gene expression and deep immunophenotyping were assayed. pDCs showed an increase of activation markers levels, interferon related genes, HIV-1 restriction factors and cytokines levels after TLR stimulation in the different HIV-disease progression phenotypes. This pDC activation was prominent with CpG-C and GS-9620 and induced an increase of HIV-specific T-cell response even in VIR and INR comparable with EC. This HIV-1 specific T-cell response was associated with the upregulation of HIV-1 restriction factors and IFN-α production by pDC. These results shed light on the mechanisms associated with TLR-specific pDCs stimulation associated with the induction of a T-cell mediated antiviral response which is essential for HIV-1 eradication strategies. This work was supported by Gilead fellowship program, the Instituto de Salud Carlos III (Fondo Europeo de Desarrollo Regional, FEDER, "a way to make Europe") and the Red Temática de Investigación Cooperativa en SIDA and by the Spanish National Research Council (CSIC).

242 Listening to and Learning from the Community: A Model for Community Engagement and Building Trust

OBJECTIVES/GOALS: We have developed a community engagement model that embraces several core values: bi-directional, co-equal, co-created, inclusive, culturally centered, and trust. Our promotoras de salud and community health workers (CHWs) facilitate listening sessions to understand the most pressing health needs and concerns as perceived by the community. METHODS/STUDY POPULATION: Our Southern California CTSI Community Engagement team includes promotoras de salud and community health workers who are trusted individuals within our targeted communities–Latino and Black populations in South and the Eastside of Los Angeles. Listening sessions identify the community’s perceived health needs and concerns, and our team in turn delivers a workshop series that addresses those concerns. Workshops are co-developed by community members, offered in English and Spanish, and delivered both virtually and in-person in community venues. Workshop topics have included mental health, depression, anxiety in children; child development and autism; COVID-19 testing, variants, and vaccines; monkeypox; and a primer on understanding clinical research. RESULTS/ANTICIPATED RESULTS: In 2022, we held 49 workshops that delivered evidence-based information including how to access needed resources. We had a total of 1212 participants, 60% of whom were returning, meaning they had attended at least one prior workshop. An evaluation of the workshop program demonstrated that our promotoras de salud and community health workers are trusted by the community and that workshops are meeting community needs. 677 surveys were completed by participants, 87.5% of whom were female. 85% of respondents stated that they will use the information they learned in their daily life, and 90% said they would attend another workshop. Feedback from the evaluation will inform future workshop format and topics. DISCUSSION/SIGNIFICANCE: Academic-community partnerships are key to advancing health equity, especially in diverse and under-resourced communities. This is one model of community engagement, which includes promotoras de salud and CHWs that was designed to build trust, empower individuals through education, and to address the health needs as defined by the community.

Proline‐related metabolites: Towards biological diagnosis of depression

Psychiatry and Clinical NeurosciencesVolume 77, Issue 4 p. 195-195 Editorial Proline-related metabolites: Towards biological diagnosis of depression Jordi Mayneris-Perxachs, Corresponding Author Jordi Mayneris-Perxachs [email protected] orcid.org/0000-0003-3788-3815 Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, Spain Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IDIBGI), Girona, Spain CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain Correspondence: Jordi Mayneris-Perxachs, MD, PhD, Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital. Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IDIBGI). Avinguda de França s/n, 17007, Girona, Spain. Email: [email protected]Search for more papers by this authorJosé Manuel Fernández-Real, José Manuel Fernández-Real Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, Spain Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IDIBGI), Girona, Spain CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain Department of Medical Sciences, School of Medicine, University of Girona, Girona, SpainSearch for more papers by this author Jordi Mayneris-Perxachs, Corresponding Author Jordi Mayneris-Perxachs [email protected] orcid.org/0000-0003-3788-3815 Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, Spain Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IDIBGI), Girona, Spain CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain Correspondence: Jordi Mayneris-Perxachs, MD, PhD, Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital. Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IDIBGI). Avinguda de França s/n, 17007, Girona, Spain. Email: [email protected]Search for more papers by this authorJosé Manuel Fernández-Real, José Manuel Fernández-Real Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, Spain Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IDIBGI), Girona, Spain CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain Department of Medical Sciences, School of Medicine, University of Girona, Girona, SpainSearch for more papers by this author First published: 01 April 2023 https://doi.org/10.1111/pcn.13535Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume77, Issue4April 2023Pages 195-195 RelatedInformation

Cura seca versus cura en ambiente húmedo aplicadas a la cirugía menor en la exéresis de fibromas blandos: ensayo clínico aleatorizado

ObjectiveTo compare which skin tag approach tecniques, while adding a new technique, in order to find which produces less complications, less cost and an earlier healing. DesignNon-blinded randomized clinical trial with consecutive sampling. SiteÁrea Básica de Salud Balaguer. ParticipantsN = 240 skin tags. InterventionsThe corresponding randomized technique was performed and subsequent follow-up until epithelialization. Main measurementsSex, age, family history of skin tags, location of the lesion, diabetes, cost, healing time, complications and technique used. The techniques used were: cryotherapy, electrosurgery, excision with silver nitrate application (SNA) and excision with moist wound healing treatment (MWH). ResultsAccording to techniques, healing time is lower in MWH (3.3[±1.0] days) than in dry healing (cryotherapy 4.5[±2.3] days, electrosurgery 8.2[±4, 2] days and SNA 10.7 [±4.8] days), p < 0.001. There was also a significant difference in the number of complications in MWH (0.0%) compared to dry-healing techniques: cryotherapy 1 (3.0%), electrosurgery 4 (11.4%), SNA 22 (57.9%), p < 0.001. Finally, a lower economic cost was observed in skin tags treated with MWH (146[±9.0] euros) versus those treated with dry cure (cryotherapy 235[±22.2] euros, electrosurgery 272[±41.1] euros, SNA 213[±43.2] euros), p < 0.001. ConclusionsTreatment of skin tags by MWH is the best technique to treat these lesions because of its shorter healing time, lower cost and fewer complications. SNA stands out as the technique that has the highest number of complications and the longest healing time.