Using Wearable Devices to Profile Demographic-Specific Recovery After Pediatric Appendectomy.

INTRODUCTION: Counseling patients and parents about the postoperative recovery expectations for physical activity after pediatric appendectomy varies significantly and is not specific to patients' demographic characteristics. Consumer wearable devices (CWD) can be used to objectively assess patients' normative postoperative recovery of physical activity. This study aimed to develop demographic-specific normative physical activity recovery trajectories using CWD in pediatric patients undergoing appendectomy. METHODS: Children ages 3-18 y old undergoing laparoscopic appendectomy for acute appendicitis were recruited. Patients wore a Fitbit device for 21 d postoperatively and daily step counts were measured. Patients with postoperative complications were excluded. Segmented regression models were fitted and time-to-plateau was estimated for patients with simple and complicated appendicitis separately for each age group, sex, race/ethnicity, and body mass index category. RESULTS: Among 147 eligible patients; 76 (51.7%) were female, 86 (58.5%) were in the younger group, and 79 (53.7%) had complicated appendicitis. Patients 3-11 y old demonstrated a faster trajectory to a physical activity plateau compared to those 12-18 in both simple (postoperative day [POD] 9 versus POD 17) and complicated appendicitis (POD 17 versus POD 21). Males and females had a similar postoperative recovery trajectory in simple and complicated appendicitis. There was no clear pattern differentiating trajectories based on race/ethnicity. Overweight/obese patients demonstrated a slower recovery trajectory in simple appendicitis. CONCLUSIONS: This study demonstrates that factors other than the disease itself, such as age, may affect recovery, suggesting the need for more tailored discharge instructions. CWDs can improve our understanding of recovery and allow for better data-driven counseling perioperatively.

Consumer Wearables Define a Normative Recovery Trajectory Following the Modified Nuss Procedure.

INTRODUCTION: The modified Nuss procedure is an elective procedure associated with a lengthy recovery, uncontrolled pain, and risk of infrequent, yet life-threatening complications. The absence of objective measures of normative postoperative recovery creates uncertainty about the postdischarge period, which remains highly dependent on the patients' and their caregivers' expectations and management of recovery. We aimed to describe an objective-normative, physical activity recovery trajectory after the modified Nuss procedure, using step counts from the Fitbit. METHODS: This observational study enrolled children ≤18 y with pectus excavatum who underwent the modified Nuss procedure from 2021 to 2022. The Fitbit was worn for 21 postoperative days. Postdischarge outcomes and health-care utilization were evaluated. For patients without postoperative complications, piecewise linear regression analysis was conducted to generate a normative recovery trajectory model of daily step counts. RESULTS: Of 80 patients enrolled, 66 (86%) met eligibility criteria (mean age, 15.1 ± 1.3 y; 89.4% male, 62.1% non-Hispanic White). The mean number of telephone and electronic message encounters regarding concerns with the patient's recovery within 30 d postoperatively was 2.1 (standard deviation = 2.7). Ten patients (15.2%) returned to the emergency department (ED) within the 30-d postoperative period. Seven patients (10.6%) presented to the ED one time, and three patients (4.5%) presented to the ED twice. Thirty-day readmission rate was four patients (6.0%). Piecewise regression model showed that patients without complications steadily increased their daily step count on each postoperative day and plateaued on day 18. CONCLUSIONS: We have developed a normative recovery trajectory following the modified Nuss procedure using step count data collected by a consumer wearable device. This offers the potential to inform preoperative patient expectations and reduce avoidable health-care utilization through informed preoperative counseling, thus laying the ground work for the use of consumer wearable devices as a postdischarge remote monitoring tool.

Lessons learnt from the process of designing care coordination interventions through participatory action research in public healthcare networks of six Latin American countries.

BACKGROUND: The participation of health professionals in designing interventions is considered vital to effective implementation, yet in areas such as clinical coordination is rarely promoted and evaluated. This study, part of Equity-LA II, aims to analyse the design process of interventions to improve clinical coordination, taking a participatory-action-research (PAR) approach, in healthcare networks of Argentina, Brazil, Chile, Colombia, Mexico and Uruguay. This participatory process was planned in four phases, led by a local steering committee (LSC): (1) dissemination of problem analysis results and creation of professionals' platform, (2) selection of problems and intervention (3) intervention design and planning (4) adjustments after evaluation of first implementation stage. METHODS: A descriptive qualitative study based on documentary analysis, using a topic guide, was conducted in each intervention network. Documents produced regarding the intervention design process were selected. Thematic content analysis was conducted, generating mixed categories taken from the topic guide and identified from data. Main categories were LSC characteristics, type of design process (phases, participants' roles, methods) and associated difficulties, coordination problems and interventions selected. RESULTS: LSCs of similar composition (managers, professionals and researchers) were established, with increasing membership in Chile and high turnover in Argentina, Colombia and Mexico. Following results dissemination and selection of problems and interventions (more participatory in Chile and Colombia: 200-479 participants), the interventions were designed and planned, resulting in three different types of processes: (1) short initial design with adjustments after first implementation stage, in Colombia, Brazil and Mexico; (2) longer, more participatory process, with multiple cycles of action/reflection and pilot tests, in Chile; (3) open-ended design for ongoing adaptation, in Argentina and Uruguay. Professionals' time and the political cycle were the main barriers to participation. The clinical coordination problem selected was limited communication between primary and secondary care doctors. To address it, through discussions guided by context and feasibility criteria, interventions based on mutual feedback were selected. CONCLUSIONS: As expected in a flexible PAR process, its rollout differed across countries in participation and PAR cycles. Results show that PAR can help to design interventions adapted to context and offers lessons that can be applied in other contexts.

Changes in knowledge and use of clinical coordination mechanisms between care levels in healthcare networks of Colombia.

Clinical coordination mechanisms (CCMs) have become key tools in healthcare networks for improving coordination between primary care (PC) and secondary care (SC) and are particularly relevant in health systems with highly fragmented healthcare provision. However, their implementation has been little studied to date in Latin America and particularly in Colombia. This study analyses the level of knowledge and use of CCMs between care levels and their changes between 2015 and 2017 in two public healthcare networks in Bogotá, Colombia. Comparison of two cross-sectional studies based on surveys among PC and SC doctors working in their networks (174 doctors per network/year). The COORDENA questionnaire was used for measuring knowledge concerning CCMs and the frequency of use and difficulties involved in using referral/reply letters (R/RLs) and hospital discharge reports (HDRs). Descriptive bivariate analysis and Poisson regression models with robust variance were used for analysing differences between networks and years. The results for both networks and years revealed greater knowledge and use of information coordination mechanisms than those regarding clinical management coordination (though their knowledge increased in 2017). Although widely known and used, significant problems regarding infrequent and late receipt of RLs and HDRs in PC as well as the poor quality of their contents limits their effective use, which may affect the quality of care. Strategies are required to improve CCMs use.

The PI3Kδ Inhibitor Idelalisib Diminishes Platelet Function and Shows Antithrombotic Potential.

BACKGROUND: Clinical management of ischemic events and prevention of vascular disease is based on antiplatelet drugs. Given the relevance of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) as a candidate target in thrombosis, the main goal of the present study was to identify novel antiplatelet agents within the existing inhibitors blocking PI3K isoforms. METHODS: We performed a biological evaluation of the pharmacological activity of PI3K inhibitors in platelets. The effect of the inhibitors was evaluated in intracellular calcium release and platelet functional assays, the latter including aggregation, adhesion, and viability assays. The in vivo drug antithrombotic potential was assessed in mice undergoing chemically induced arterial occlusion, and the associated hemorrhagic risk evaluated by measuring the tail bleeding time. RESULTS: We show that PI3K Class IA inhibitors potently block calcium mobilization in human platelets. The PI3K p110δ inhibitor Idelalisib inhibits platelet aggregation mediated by ITAM receptors GPVI and CLEC-2, preferentially by the former. Moreover, Idelalisib also inhibits platelet adhesion and aggregation under shear and adhesion to collagen. Interestingly, an antithrombotic effect was observed in mice treated with Idelalisib, with mild bleeding effects at high doses of the drug. CONCLUSION: Idelalisib may have antiplatelet effects with minor bleeding effects, which provides a rationale to evaluate its antithrombotic efficacy in humans.

Can care coordination across levels be improved through the implementation of participatory action research interventions? Outcomes and conditions for sustaining changes in five Latin American countries.

BACKGROUND: Finding new strategies for care integration has become a policy priority for many fragmented health systems in Latin America. Although the implementation of interventions through a participatory action research (PAR) approach is considered to be more effective in achieving organizational change, its application is scarce. This study, part of the research project Equity-LA II, aims to analyze the impact of PAR interventions on care coordination across levels, and key aspects for their sustainability and transferability, from the stakeholder viewpoint in healthcare networks of Brazil, Chile, Colombia, Mexico and Uruguay. Different interventions were designed and implemented through a PAR process to improve communication and clinical agreement between primary care and secondary care doctors: joint meetings to discuss clinical cases and/or training; shared care guidelines; offline virtual consultations; a referral and reply letter; and an induction program. METHODS: A qualitative, descriptive-interpretative study was conducted in the healthcare network of each country. Focus groups and semi-structured individual interviews were conducted with a criterion sample of participants: local steering committee (29) and professional platform members (28), other health professionals (49) and managers (28). Thematic content analysis was conducted, segmented by country and type of intervention. RESULTS: Informants highlighted that joint meetings based on reflexive methods contributed substantially to improving contextually relevant elements of clinical management coordination - communication in patient follow-up, clinical agreement, appropriateness of referrals - and also administrative coordination. The meetings, alongside the PAR process, also helped to improve interaction between professionals - knowing each other personally and mutual trust - thus fostering willingness to collaborate. The PAR approach, moreover, served to spread awareness of the coordination problems and need for intervention, encouraging greater commitment and interest in participating. No noteworthy contributions were identified in remaining interventions due to low uptake. A necessary condition for the sustainability and replicability was that PAR process had to be used appropriately in a favourable context. CONCLUSIONS: Evidence is provided on the substantial contribution of interventions to improving locally relevant clinical coordination elements and professional interaction when implemented through an adequate PAR process (in terms of time, method and participation levels), a necessary condition for their sustainability and replicability.

A Repressor Protein Complex Regulates Leaf Growth in Arabidopsis.

Cell number is an important determinant of final organ size. In the leaf, a large proportion of cells are derived from the stomatal lineage. Meristemoids, which are stem cell-like precursor cells, undergo asymmetric divisions, generating several pavement cells adjacent to the two guard cells. However, the mechanism controlling the asymmetric divisions of these stem cells prior to differentiation is not well understood. Here, we characterized PEAPOD (PPD) proteins, the only transcriptional regulators known to negatively regulate meristemoid division. PPD proteins interact with KIX8 and KIX9, which act as adaptor proteins for the corepressor TOPLESS. D3-type cyclin encoding genes were identified among direct targets of PPD2, being negatively regulated by PPDs and KIX8/9. Accordingly, kix8 kix9 mutants phenocopied PPD loss-of-function producing larger leaves resulting from increased meristemoid amplifying divisions. The identified conserved complex might be specific for leaf growth in the second dimension, since it is not present in Poaceae (grasses), which also lack the developmental program it controls.

Room temperature sintering of polar ZnO nanosheets: I-evidence.

Polar ZnO nanosheets of a high specific surface area (∼120 m2 g-1) were subjected to storage under different atmospheres at room temperature and analyzed for changes in their textural and crystal properties. During their storage under laboratory conditions (in closed transparent polypropylene vials kept under the light of the laboratory on worktop tables) the nanosheets lost up to 75% of their specific surface area in approximately two months, with most of the loss occurring during the first two weeks. The narrow mesoporosity (∼5 nm pore size) became filled with ZnO during the process. No loss or gain in weight was detected. The loss of specific surface area took place under all of the atmospheres assayed, in the following order: moist air (with or without light) > moist CO2-free atmosphere (with or without light and/or oxygen) > dry CO2-free oxygen-containing atmosphere (with or without light) > dry inert atmosphere (with light) > dry inert atmosphere (in the dark). During storage the ZnO crystals grew mainly by the partial merging of their polar surfaces in a process triggered by the action of moisture, oxygen and, in the absence of these two agents, light. The mechanism of this intriguing phenomenon will be analyzed in detail in the second part of this work.

Room temperature sintering of polar ZnO nanosheets: II-mechanism.

In a previous work by the authors (A. Fernández-Pérez el al., Room temperature sintering of polar ZnO nanosheets: I-evidence, 2017, DOI: 10.1039/C7CP02306E), polar ZnO nanosheets were stored at room temperature under different atmospheres and the evolution of their textural and crystal properties during storage was followed. It was found that the specific surface area of the nanosheets drastically decreased during storage, with a loss of up to 75%. The ZnO crystals increased in size mainly through the partial merging of their polar surfaces at the expense of narrow mesoporosity, in a process triggered by the action of moisture, oxygen and, in their absence, by light. In the present work, a set of spectroscopic techniques (FTIR, Raman and XPS) has been used in an attempt to unravel the mechanism behind this spontaneous sintering process. The mechanism starts with the molecular adsorption of water, which takes place on Zn atoms close to oxygen vacancies on the (100) surface, where H2O dissociates to form two hydroxyl groups and to heal one oxygen vacancy. This process triggers the room temperature migration of Zn interstitials towards the outer surface of the polar region. What were previously interstitial Zn atoms now gradually occupy the mesopores, with interstitial oxygen being used to build up the O sublattice until total occupancy of the narrow mesoporosity is achieved.

NINJA connects the co-repressor TOPLESS to jasmonate signalling.

Jasmonoyl-isoleucine (JA-Ile) is a plant hormone that regulates a broad array of plant defence and developmental processes. JA-Ile-responsive gene expression is regulated by the transcriptional activator MYC2 that interacts physically with the jasmonate ZIM-domain (JAZ) repressor proteins. On perception of JA-Ile, JAZ proteins are degraded and JA-Ile-dependent gene expression is activated. The molecular mechanisms by which JAZ proteins repress gene expression remain unknown. Here we show that the Arabidopsis JAZ proteins recruit the Groucho/Tup1-type co-repressor TOPLESS (TPL) and TPL-related proteins (TPRs) through a previously uncharacterized adaptor protein, designated Novel Interactor of JAZ (NINJA). NINJA acts as a transcriptional repressor whose activity is mediated by a functional TPL-binding EAR repression motif. Accordingly, both NINJA and TPL proteins function as negative regulators of jasmonate responses. Our results point to TPL proteins as general co-repressors that affect multiple signalling pathways through the interaction with specific adaptor proteins. This new insight reveals how stress-related and growth-related signalling cascades use common molecular mechanisms to regulate gene expression in plants.

Do existing mechanisms contribute to improvements in care coordination across levels of care in health services networks? Opinions of the health personnel in Colombia and Brazil.

BACKGROUND: The fragmentation of healthcare provision has given rise to a wide range of interventions within organizations to improve coordination across levels of care, primarily in high income countries but also in some middle and low-income countries. The aim is to analyze the use of coordination mechanisms in healthcare networks and its implications for the delivery of health care. This is studied from the perspective of health personnel in two countries with different health systems, Colombia and Brazil. METHODS: A qualitative, exploratory and descriptive-interpretative study was conducted, based on a case study of healthcare networks in two municipalities in each country. Individual semi-structured interviews were conducted with a three stage theoretical sample of a) health (112) and administrative (66) professionals of different care levels, and b) managers of providers (42) and insurers (14). A thematic content analysis was conducted, segmented by cases, informant groups and themes. RESULTS: The results show that care coordination mechanisms are poorly implemented in general. However, the results are marginally better in certain segments of the Colombian networks analyzed (ambulatory centres with primary and secondary care co-location owned by or tied to the contributory scheme insurers, and public providers of the subsidized scheme); and in the network of the state capital in Brazil. Professionals point to numerous problems in the use of existing mechanisms, such as the insufficient recording of information in referral forms, low frequency and level of participation in shared clinical sessions, low adherence to the few available clinical guidelines and the lack of or inadequate referral of patients by the patient referral centres, particularly in the Brazilian networks. The absence or limited use of care coordination mechanisms leads, according to informants, to the inadequate follow-up of patients, interruptions in care and duplication of tests. Professionals use informal strategies to try to overcome these limitations. CONCLUSIONS: The results indicate not only the limited implementation of mechanisms for coordination across care levels, but also a limited use of existing mechanisms in the healthcare networks analyzed. This has a negative impact on coordination, efficiency and quality of care. Organizational changes are required in the networks and healthcare systems to address these problems.

Inequities in access to health care in different health systems: a study in municipalities of central Colombia and north-eastern Brazil.

INTRODUCTION: Health system reforms are undertaken with the aim of improving equity of access to health care. Their impact is generally analyzed based on health care utilization, without distinguishing between levels of care. This study aims to analyze inequities in access to the continuum of care in municipalities of Brazil and Colombia. METHODS: A cross-sectional study was conducted based on a survey of a multistage probability sample of people who had had at least one health problem in the prior three months (2,163 in Colombia and 2,167 in Brazil). The outcome variables were dichotomous variables on the utilization of curative and preventive services. The main independent variables were income, being the holder of a private health plan and, in Colombia, type of insurance scheme of the General System of Social Security in Health (SGSSS). For each country, the prevalence of the outcome variables was calculated overall and stratified by levels of per capita income, SGSSS insurance schemes and private health plan. Prevalence ratios were computed by means of Poisson regression models with robust variance, controlling for health care need. RESULTS: There are inequities in favor of individuals of a higher socioeconomic status: in Colombia, in the three different care levels (primary, outpatient secondary and emergency care) and preventive activities; and in Brazil, in the use of outpatient secondary care services and preventive activities, whilst lower-income individuals make greater use of the primary care services. In both countries, inequity in the use of outpatient secondary care is more pronounced than in the other care levels. Income in both countries, insurance scheme enrollment in Colombia and holding a private health plan in Brazil all contribute to the presence of inequities in utilization. CONCLUSIONS: Twenty years after the introduction of reforms implemented to improve equity in access to health care, inequities, defined in terms of unequal use for equal need, are still present in both countries. The design of the health systems appears to determine access to the health services: two insurance schemes in Colombia with different benefits packages and a segmented system in Brazil, with a significant private component.

Jasmonate signaling involves the abscisic acid receptor PYL4 to regulate metabolic reprogramming in Arabidopsis and tobacco.

The phytohormones jasmonates (JAs) constitute an important class of elicitors for many plant secondary metabolic pathways. However, JAs do not act independently but operate in complex networks with crosstalk to several other phytohormonal signaling pathways. Here, crosstalk was detected between the JA and abscisic acid (ABA) signaling pathways in the regulation of tobacco (Nicotiana tabacum) alkaloid biosynthesis. A tobacco gene from the PYR/PYL/RCAR family, NtPYL4, the expression of which is regulated by JAs, was found to encode a functional ABA receptor. NtPYL4 inhibited the type-2C protein phosphatases known to be key negative regulators of ABA signaling in an ABA-dependent manner. Overexpression of NtPYL4 in tobacco hairy roots caused a reprogramming of the cellular metabolism that resulted in a decreased alkaloid accumulation and conferred ABA sensitivity to the production of alkaloids. In contrast, the alkaloid biosynthetic pathway was not responsive to ABA in control tobacco roots. Functional analysis of the Arabidopsis (Arabidopsis thaliana) homologs of NtPYL4, PYL4 and PYL5, indicated that also in Arabidopsis altered PYL expression affected the JA response, both in terms of biomass and anthocyanin production. These findings define a connection between a component of the core ABA signaling pathway and the JA responses and contribute to the understanding of the role of JAs in balancing tradeoffs between growth and defense.

Chest Wall Dermatitis Patterns Following Thoracoscopic Intercostal Nerve Cryoablation for Surgical Correction of Pectus Excavatum.

BACKGROUND: Intercostal nerve cryoablation (INC) has been shown to reduce postoperative pain and length of stay following surgical correction of pectus excavatum (SCOPE). Some patients have developed chest wall dermatological symptoms after INC that can be mistaken for metal allergy or infection. The purpose of this study is to report the symptoms, severity, incidence, and treatment of post-cryoablation dermatitis. METHODS: A retrospective single institution review was performed for patients who underwent SCOPE with and without INC between June 2016 and March 2023 to assess for incidence of postoperative dermatological findings. Characteristics associated with these findings were evaluated. RESULTS: During study period, 383 patients underwent SCOPE, 165 (43.1%) without INC and 218 (56.9%) with. Twenty-three (10.6%) patients who received INC developed exanthems characteristic of post-cryoablation dermatitis with two distinct phenotypes identified. No patients who underwent SCOPE without INC developed similar manifestations. Early dermatitis, characterized by a painless, erythematous, and blanching rash across the anterior thorax, was observed in 16 patients, presenting on median postoperative day 6.0 [IQR 6.0-8.5], with median time to resolution of 23.0 [IQR 12-71.0] days after symptom onset. Late dermatitis, characterized by hyperpigmentation spanning the anterior thorax, was observed in 7 patients, presenting on median postoperative day 129.0 [IQR 84.5-240.0], with median time to resolution of 114.0 [IQR 48.0-314.3] days. CONCLUSION: This is the first report of dermatological manifestations following SCOPE with INC, a phenomenon of unknown etiology and no known long-term sequela. In our experience, it is self-resolving and lacks systemic symptoms suggesting observation alone is sufficient for resolution. LEVEL OF EVIDENCE: IV.

Utility of White Light Scanning as an Alternative to Computed Tomography to Evaluate Severity of Pectus Excavatum Deformity.

BACKGROUND: Pectus excavatum (PE) severity and surgical candidacy are determined by computed tomography (CT)-delineated Haller Index (HI) and Correction Index (CI). White light scanning (WLS) has been proposed as a non-ionizing alternative. The purpose of this retrospective study is to create models to determine PE severity using WLS as a non-ionizing alternative to CT. METHODS: Between November 2015 and February 2023, CT and WLS were performed for children ≤18 years undergoing evaluation at a high-volume, chest-wall deformity clinic. Separate quadratic discriminate analysis models were developed to predict CT HI ≥ 3.25 and CT CI ≥ 28% indicating surgical candidacy. Two bootstrap forest models were trained on WLS measurements and patient demographics to predict CT HI and CT CI values then compared to actual index values by intraclass correlation coefficient (ICC). RESULTS: In total, 242 patients were enrolled (86.4% male, mean [SD] age 15.2 [1.3] years). Quadratic discriminate analysis models predicted CT HI ≥ 3.25 with specificity = 91.7%, PPV = 97.7% (AUC = 0.91), and CT CI ≥ 28% with specificity = 92.3%, PPV = 93.5% (AUC = 0.84). Bootstrap forest model predicted CT HI with training dataset ICC (95% CI) = 0.91 (0.88-0.93, R2 = 0.85) and test dataset ICC (95% CI) = 0.86 (0.71-0.94, R2 = 0.77). For CT CI, training dataset ICC (95% CI) = 0.91 (0.81-0.93, R2 = 0.86) and test dataset ICC (95% CI) = 0.75 (0.50-0.88, R2 = 0.63). CONCLUSIONS: Using noninvasive and nonionizing WLS imaging, we can predict PE severity at surgical threshold with high specificity obviating the need for CT. Furthermore, we can predict actual CT HI and CI with moderate-excellent reliability. We anticipate this point-of-care tool to obviate the need for most cross-sectional imaging during surgical evaluation of PE. LEVEL OF EVIDENCE: Level III. STUDY TYPE: Study of Diagnostic Test.

Frequency of Dengue Virus-Specific T Cells is related to Infection Outcome in Endemic Settings.

Dengue is widespread in tropical and subtropical regions globally and leads to a considerable burden of disease. Annually, dengue virus (DENV) causes up to 400 million infections, of which ~25% present with clinical symptoms ranging from mild to fatal. Despite its significance as a growing public health concern, the development of effective DENV vaccines has been highly challenging. One of the reasons is the lack of comprehensive understanding of the influence exerted by prior DENV infections and immune responses with cross-reactive properties. To investigate this, we collected samples from a pediatric cohort study in dengue-endemic Managua, Nicaragua. We characterized T cell responses in a group of 71 healthy children who had previously experienced one or more natural DENV infections and who, within one year after sample collection, had a subsequent DENV infection that was either symptomatic (n=25) or inapparent (n=46, absence of clinical disease). Thus, our study was designed to investigate the impact of pre-existing DENV specific T cell responses on the clinical outcomes of subsequent DENV infection. We assessed the DENV specific T cell responses using an activation-induced marker assay (AIM). Children who had experienced only one prior DENV infection displayed heterogeneous DENV specific CD4+ and CD8+ T cell frequencies. In contrast, children who had experienced two or more DENV infections showed significantly higher frequencies of DENV specific CD4+ and CD8+ T cells that were associated with inapparent as opposed to symptomatic outcomes in the subsequent DENV infection. Taken together, these findings demonstrate the protective role of DENV specific T cells against symptomatic DENV infection and constitute an advancement toward identifying protective immune correlates against dengue fever and clinical disease.

Effects of managed care mechanisms on access to healthcare: results from a qualitative study in Colombia.

BACKGROUND: Managed competition has underpinned most health sector reforms aimed at improving access and efficiency, in Latin America and other countries. The aim of the paper is to analyse barriers to healthcare that emerge from the introduction of managed care mechanisms in Colombia. METHODS: Qualitative, exploratory, and descriptive-interpretative research was carried out on the basis of case studies of four healthcare networks, comprised of insurers and their providers. Individual semi-structured interviews were conducted with a theoretical sample of informants (managers, professionals, and users), between 24 and 61 per network. The final sample size was reached by saturation of information. An inductive thematic content analysis was conducted. The study areas were two municipalities of Colombia, in which most of the population live in poverty. RESULTS: A number of managed care mechanisms that act as barriers to access were identified by all informants, regardless of area and type of insurance regime. These mechanisms act directly on the patient (authorizations, fragmented insurance) or on the providers (purchasing mechanisms or limits to medical practice). The predominant mechanism appears to be related to the type of agreement established between insurers and providers. The reason for these barriers, according to informants, is insurers' search for profitability. As a consequence, there is delay in or no access to adequate treatment. This is particularly evident in secondary care. CONCLUSION: A variety of managed care strategies that effectively hinder access to healthcare have been introduced by insurers, casting doubt on the usefulness of their application in low-income countries and profit-making contexts.

Ultraviolet light spectroscopic characterization of ibuprofen acid aggregation in deionized water.

This work provides a description of the aggregation equilibria of ibuprofen acid in deionized water at temperatures between 20 and 40 °C in the 0.1-20.1 ppm concentration range. For this goal, we have made use of UV-Visible spectroscopy. A calculation algorithm was developed to obtain the aggregate orders and thermodynamic parameters from the experimental absorbance values. Monomeric ibuprofen acid was found to be absent in water solutions. In addition to the dimer, two aggregates formed by 32 and 128 monomeric units were found to co-exist in solution at the highest concentration tested. A critical micelle concentration of 7.8 ppm was estimated for this system. The appearance of the first aggregate occurs when the pH drops below the pKa value, which was determined to be 4.62. At higher ibuprofen concentrations, a sudden jump in the electrical conductivity coincides with the onset of formation of the second aggregate. A varied menu of alternatives is offered with respect to the calibration curve of ibuprofen in water, though the linear calibration of ibuprofen concentration with absorbance might be reasonably performed at 224 nm. Finally, the dissolution rate of the commercial ibuprofen used in this work was found to obey the Noyes-Whitney first order equation.

Immunization with nanovaccines containing mutated K-Ras peptides and imiquimod aggravates heterotopic pancreatic cancer induced in mice.

Purpose: The growing incidence and lethality of pancreatic cancer urges the development of new therapeutic approaches. Anti-tumoral vaccines can potentiate the immune response against the tumor, targeting specific antigens expressed only on tumor cells. In this work, we designed new vaccines for pancreatic cancer, composed by chitosan nanocapsules (CS NCs) containing imiquimod (IMQ) as adjuvant, and targeting the K-Ras mutation G12V. Experimental design: We tested the immunogenicity of our vaccines in mice, carrying different combinations of K-Ras mutated peptides. Then, we analyzed their prophylactic and therapeutic efficacy in mice bearing heterotopic pancreatic cancer. Results: Unexpectedly, although good results were observed at short time points, the different combinations of our CS NCs vaccines seemed to potentiate tumor growth and reduce survival rate. We propose that this effect could be due to an inadequate immune response, partially because of the induction of a regulatory tolerogenic response. Conclusion: Our results call for caution in the use of some NCs containing IMQ in the immunotherapy against pancreatic cancer.

Bordetella spp. block eosinophil recruitment to suppress the generation of early mucosal protection.

Bordetella spp. are respiratory pathogens equipped with immune evasion mechanisms. We previously characterized a Bordetella bronchiseptica mutant (RB50ΔbtrS) that fails to suppress host responses, leading to rapid clearance and long-lasting immunity against reinfection. This work revealed eosinophils as an exclusive requirement for RB50ΔbtrS clearance. We also show that RB50ΔbtrS promotes eosinophil-mediated B/T cell recruitment and inducible bronchus-associated lymphoid tissue (iBALT) formation, with eosinophils being present throughout iBALT for Th17 and immunoglobulin A (IgA) responses. Finally, we provide evidence that XCL1 is critical for iBALT formation but not maintenance, proposing a novel role for eosinophils as facilitators of adaptive immunity against B. bronchiseptica. RB50ΔbtrS being incapable of suppressing eosinophil effector functions illuminates active, bacterial targeting of eosinophils to achieve successful persistence and reinfection. Overall, our discoveries contribute to understanding cellular mechanisms for use in future vaccines and therapies against Bordetella spp. and extension to other mucosal pathogens.