Contribution of environmental determinants to the risk of developing type 2 diabetes mellitus in a life-course perspective: a systematic review protocol.

BACKGROUND: Prevention policies against type 2 diabetes mellitus (T2DM) focus solely on individual healthy lifestyle behaviours, while an increasing body of research recognises the involvement of environmental determinants (ED) (cultural norms of land management and planning, local foodscape, built environment, pollution, and neighbourhood deprivation). Precise knowledge of this relationship is essential to proposing a prevention strategy integrating public health and spatial planning. Unfortunately, issues related to the consistency and synthesis of methods, and results in this field of research limit the development of preventive strategies. This systematic review aims to improve knowledge about the relationship between the risk of developing T2DM in adulthood and long-term exposure to its ED during childhood or teenage years. METHODS: This protocol is presented according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) tools. PubMed, Embase, CINAHL, Web of Science, EBSCO, and grey literature from the Laval University Libraries databases will be used for data collection on main concepts such as 'type 2 diabetes mellitus', 'zoning' or 'regional, urban, or rural areas land uses', 'local food landscape', 'built environment', 'pollution', and 'deprivation'. The Covidence application will store the collected data for selection and extraction based on the Population Exposure Comparator Outcome and Study design approach (PECOS). Studies published until December 31, 2023, in English or French, used quantitative data about individuals aged 18 and over that report on T2DM, ED (cultural norms of land management and planning, local foodscape, built environment, and neighbourhood deprivation), and their association (involving only risk estimators) will be included. Then, study quality and risk of bias will be conducted according to the combined criteria and ratings from the ROBINS-E (Risk of Bias in Non-randomised Studies-of Exposures) tools and the 'Effective Public Health Practice Project' (EPHPP). Finally, the analytical synthesis will be produced using the 'Synthesis Without Meta-analysis' (SWiM) guidelines. DISCUSSION: This systematic review will summarise available evidence on ED associated with T2DM. The results will contribute to improving current knowledge and developing more efficient cross-sectoral interventions in land management and public health in this field of research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023392073.

Optimizing Fecal Occult Blood Test (FOBT) Colorectal Cancer Screening Using Gut Bacteriome as a Biomarker.

BACKGROUND: Colorectal cancer (CRC) is a major cause of cancer mortality in the world. One of the most widely used screening tests for CRC is the immunochemical fecal occult blood test (iFOBT), which detects human hemoglobin from patient's stool sample. Although it is highly efficient in detecting blood from patients with gastro-intestinal lesions, such as polyps and cancers, the iFOBT has a high rate of false positive discovery. Recent studies suggested gut bacteria as a promising noninvasive biomarker for improving the diagnosis of CRC. In this study, we examined the composition of gut bacteria using iFOBT leftover from patients undergoing screening test along with a colonoscopy. METHODS: After collecting data from more than 800 patients, we considered 4 groups for this study. The first and second groups were respectively "healthy" in which the patients had either no blood in their stool or had blood but no lesions. The third and fourth groups of patients had both blood in their stools with precancerous and cancerous lesions and considered either as low-grade and high-grade lesion groups, respectively. An amplification of 16S rRNA (V4 region) gene was performed, followed by sequencing along with various statistical and bioinformatic analysis. RESULTS: We analyzed the composition of the gut bacteriome at phylum, class, genus, and species levels. Although members of the Firmicute phylum increased in the 3 groups compared to healthy patients, the phylum Actinobacteriota was found to decrease. Moreover, Blautia obeum and Anaerostipes hadrus from the phylum Firmicutes were increased and Collinsella aerofaciens from phylum Actinobacteriota was found decreased when healthy group is compared to the patients with high-grade lesions. Finally, among the 5 machine learning algorithms used to perform our analysis, both elastic net (AUC > 0.7) and random forest (AUC > 0.8) performs well in differentiating healthy patients from 3 other patient groups having blood in their stool. CONCLUSION: Our study integrates the iFOBT screening tool with gut bacterial composition to improve the prediction of CRC lesions.

A nod to the bond between NOD2 and mycobacteria.

Mycobacteria are responsible for several human and animal diseases. NOD2 is a pattern recognition receptor that has an important role in mycobacterial recognition. However, the mechanisms by which mutations in NOD2 alter the course of mycobacterial infection remain unclear. Herein, we aimed to review the totality of studies directly addressing the relationship between NOD2 and mycobacteria as a foundation for moving the field forward. NOD2 was linked to mycobacterial infection at 3 levels: (1) genetic, through association with mycobacterial diseases of humans; (2) chemical, through the distinct NOD2 ligand in the mycobacterial cell wall; and (3) immunologic, through heightened NOD2 signaling caused by the unique modification of the NOD2 ligand. The immune response to mycobacteria is shaped by NOD2 signaling, responsible for NF-κB and MAPK activation, and the production of various immune effectors like cytokines and nitric oxide, with some evidence linking this to bacteriologic control. Absence of NOD2 during mycobacterial infection of mice can be detrimental, but the mechanism remains unknown. Conversely, the success of immunization with mycobacteria has been linked to NOD2 signaling and NOD2 has been targeted as an avenue of immunotherapy for diseases even beyond mycobacteria. The mycobacteria-NOD2 interaction remains an important area of study, which may shed light on immune mechanisms in disease.

Mice Dually Disrupted for Nod2 and Mincle Manifest Early Bacteriological Control but Late Susceptibility During Mycobacterium tuberculosis Infection.

Pattern recognition receptors Mincle and NOD2 have been implicated in mycobacterial immunity. However, knockout (KO) animal infection studies with Mycobacterium tuberculosis (Mtb) have had mild/delayed phenotypes. Given that genetic susceptibility to infectious diseases can be polygenic, we hypothesized that murine double knockout (DKO) of Mincle and Nod2 would result in exacerbation of altered immunity to mycobacterial infection leading to a more extreme phenotype than either KO alone. To test this hypothesis, we monitored bacterial burden, immune responses and survival following in vivo infections with Mtb in DKO mice for comparison to wildtype (WT) and single KOs. Bacterial burden and immune responses were not significantly affected at 3 and 6 weeks after infection in all mutant mice. At later timepoints, Nod2-KO mice had reduced survival compared to wildtype mice, and Mincle-KO survival was intermediate. Unexpectedly, dual disruption had no further effect; rather, DKO mice phenocopied Nod2-KO mice. We observed that Mtb-related death, exclusively in mice with disrupted Nod2, was accompanied by greater pulmonary cell death and distinct large necrotic foci. Therefore, determining how these receptors contribute to mycobacterial resistance will require analysis of immunophenotypes and their consequences on host pathology.

Revisiting Pierre Gy's formula (TOS) - A return to size-density classes for applications to contaminated soils, coated particular aggregates and mixed material systems.

For some real-world material systems, estimations of the incompressible sampling variance based on Gy's classical s2(FSE) formula from the Theory of Sampling (TOS) show a significant discrepancy with empirical estimates of sampling variance. In instances concerning contaminated soils, coated particular aggregates and mixed material systems, theoretical estimates of sampling variance are larger than empirical estimates, a situation which does not have physical meaning in TOS. This has led us to revisit the development of estimates of s2(FSE) from this famous constitutional heterogeneity equation and explore the use of size-density classes for mixed material systems (mixtures of both analyte-enriched and coated particles), an approach which has been mostly unused since Gy's original derivation. This approach makes it possible to avoid taking into account the granulometric and liberation factors from Gy's classical treatment, and present grounds for criticising the use of 'standard' input values of critical parameters such as f: = 0.5, and g: = 0.25. But, as always, the "liberation factor" (l) issue still plays an important role, which is paid due attention. The constitutional heterogeneity formula based on size-density classes is presented in a form that allows for easy implementation in practice, within specified limitations. We present extensive experimental results from real-world systems. Using the "SDCD model" with published data reproduced the relative sampling variances calculated for the standard "mineral-like matrices", but more importantly corrected the relative sampling variance calculated for real contaminants by several orders of magnitudes. In all cases, the recalculated relative sampling variances were decreased to below their corresponding experimental measurements, now fully as expected from TOS, substantiating our development.

Sampling particulate matter for analysis - Controlling uncertainty and bias using the theory of sampling.

Sampling particulate matter for measuring the content of an analyte is a routine operation in many fields of engineering and science. However, sampling can lead to important bias and variance in concentration estimation because of sampling errors stemming from particulate matter heterogeneity. The goal of this study was to quantify bias, reproducibility and the degree of representativeness of a probabilistic sampling (PS) technique following principles from the Theory of sampling (TOS) and grab sampling (GS). PS was designed to control sampling errors, while GS did not exert any control over them. GS also included a step of sieve screening, which is common during sampling in some fields (e.g. soil sampling). Both techniques were used with two different analytes, namely steel microspheres and copper sulfate, at two different concentrations, in order to assess sampling errors and sampling performance. The sampling method had the most significant effect on sampling bias and relative variance, and therefore, on the degree of sampling representativeness. The most important result is the demonstration that probabilistic sampling improves the degree of representativeness of concentrations measurements by more than two orders of magnitudes by significantly decreasing bias and relative variance. The lot containing the physical analyte lead to larger bias and relative variance compared to the lot containing the chemical analyte. GS resulted in largely biased results and a poor degree of representativeness. The results have also highlighted a significant problem associated with the screening of larger particles as performed in GS. This alteration of the primary sample decreased the variability of the resulting concentration measurements, but it also biased them significantly.

Underwhelming or Misunderstood? Genetic Variability of Pattern Recognition Receptors in Immune Responses and Resistance to Mycobacterium tuberculosis.

Human genetic control is thought to affect a considerable part of the outcome of infection with Mycobacterium tuberculosis (Mtb). Most of us deal with the pathogen by containment (associated with clinical "latency") or sterilization, but tragically millions each year do not. After decades of studies on host genetic susceptibility to Mtb infection, genetic variation has been discovered to play a role in tuberculous immunoreactivity and tuberculosis (TB) disease. Genes encoding pattern recognition receptors (PRRs) enable a consistent, molecularly direct interaction between humans and Mtb which suggests the potential for co-evolution. In this review, we explore the roles ascribed to PRRs during Mtb infection and ask whether such a longstanding and intimate interface between our immune system and this pathogen plays a critical role in determining the outcome of Mtb infection. The scientific evidence to date suggests that PRR variation is clearly implicated in altered immunity to Mtb but has a more subtle role in limiting the pathogen and pathogenesis. In contrast to 'effectors' like IFN-γ, IL-12, Nitric Oxide and TNF that are critical for Mtb control, 'sensors' like PRRs are less critical for the outcome of Mtb infection. This is potentially due to redundancy of the numerous PRRs in the innate arsenal, such that Mtb rarely goes unnoticed. Genetic association studies investigating PRRs during Mtb infection should therefore be designed to investigate endophenotypes of infection - such as immunological or clinical variation - rather than just TB disease, if we hope to understand the molecular interface between innate immunity and Mtb.

Determinants of pain assessment documentation in intensive care units.

PURPOSE: The underassessment of pain is a major barrier to effective pain management, and the lack of pain assessment documentation has been associated with negative patient outcomes. This study aimed to 1) describe the contextual factors related to pain assessment and management in five Québec intensive care units (ICUs); 2) describe their pain assessment documentation practices; and 3) identify sociodemographic and clinical determinants related to pain assessment documentation. METHODS: A descriptive-correlational retrospective design was used. Sociodemographic data (i.e., age, sex), clinical data (i.e., diagnosis, mechanical ventilation, level of consciousness, severity of illness, opioids, sedatives), and pain assessments were extracted from 345 medical charts of ICU admissions from five teaching hospitals between 2017 and 2019. Descriptive statistics and multiple linear regression were performed. RESULTS: All sites reported using the 0-10 numeric rating scale, but the implementation of a behavioural pain scale was variable across sites. A median of three documented pain assessments were performed per 24 hr, which is below the minimal recommendation of eight to 12 pain assessments per 24 hr. Overall, pain assessment was present in 70% of charts, but only 20% of opioid doses were followed by documented pain reassessment within one hour post-administration. Higher level of consciousness (ß = 0.37), using only breakthrough doses (ß = 0.24), and lower opioid doses (ß = -0.21) were significant determinants of pain assessment documentation (adjusted R2 = 0.25). CONCLUSION: Pain assessment documentation is suboptimal in ICUs, especially for patients unable to self-report or those receiving higher opioid doses. Study findings highlight the need to implement tools to optimize pain assessment and documentation.

RéSUMé: OBJECTIF: La sous-évaluation de la douleur constitue un obstacle majeur à une gestion efficace de la douleur, et le manque de documentation de l'évaluation de la douleur a été associé à des conséquences défavorables pour les patients. Cette étude visait à : 1) décrire les facteurs contextuels liés à l'évaluation et à la gestion de la douleur dans cinq unités de soins intensifs (USI) du Québec; 2) décrire leurs pratiques de documentation de l'évaluation de la douleur; et 3) identifier les déterminants sociodémographiques et cliniques liés à la documentation de l'évaluation de la douleur. MéTHODE: Un devis de recherche rétrospectif descriptif-corrélationnel a été utilisé. Les données sociodémographiques (c.-à-d. l'âge, le sexe), les données cliniques (c.-à-d. le diagnostic, la ventilation mécanique, le niveau de conscience, la gravité de la maladie, les opioïdes, les sédatifs) et les évaluations de la douleur ont été extraites de 345 dossiers médicaux avec admissions à l'USI de cinq hôpitaux universitaires entre 2017 et 2019. Des statistiques descriptives et une régression linéaire multiple ont été effectuées. RéSULTATS: Tous les sites ont déclaré utiliser l'échelle d'évaluation numérique de 0 à 10, mais l'implantation d'une échelle de douleur comportementale variait d'un site à un autre. Une médiane de trois évaluations de douleur étaient documentées par 24 heures, ce qui est inférieur à la recommandation minimale de huit à 12 évaluations de douleur par 24 heures. Dans l'ensemble, l'évaluation de la douleur était présente dans 70 % des dossiers, mais seulement 20 % des doses d'opioïdes étaient suivies d'une réévaluation documentée de la douleur dans l'heure suivant leur'administration. Un niveau de conscience plus élevé (ß = 0,37), l'utilisation exclusive d'entredoses d'opioïdes pour les percées de douleur (ß = 0,24) et des doses d'opioïdes plus faibles (ß = -0,21) ont constitué les déterminants significatifs dans la documentation de l'évaluation de la douleur (R2 ajusté = 0,25). CONCLUSION: La documentation de l'évaluation de la douleur est sous-optimale dans les USI, en particulier pour les patients incapables de s'exprimer ou ceux qui reçoivent des doses plus élevées d'opioïdes. Les résultats de cette étude soulignent l'importance d'implanter des outils pour optimiser l'évaluation et la documentation de la douleur.

Analysis of implementation outcomes of quality improvement initiatives in Haiti: the fingerprint initiative.

OBJECTIVE: To assess the process and outcomes of the implementation of an electronic fingerprint initiative as part of quality improvement in three health facilities in the Northern Department of Haiti, in terms of its acceptability, adoption, feasibility, fidelity, and sustainability. In Haiti, poor attendance of the healthcare workforce is a nationwide problem, closely related to the quality of care. Three health institutions have tried to implement an electronic fingerprint system to monitor and improve attendance. METHODS: An exploratory and qualitative descriptive study of the implementation outcomes of the fingerprint initiative. It was based on semi-structured interviews and one group discussion using purposeful sampling techniques to recruit participants, and an open coding system and deductive approach to analyze the data using ATLAS.ti 8. RESULTS: The fingerprint initiative was successfully implemented in a non-governmental organization supported health facility but, despite some planning, it was never implemented in the public health facilities. The acceptability of the implementation was high in the not-for-profit organization and low in the public settings, mostly in relation to the presence of champions and the leadership at each health facility. CONCLUSIONS: We recommend more involvement of the leadership of health facilities in the different phases of the implementation process in order to guarantee acceptability, adoption, fidelity and sustainabiliy. More research is needed to articulate this technology-driven initiative in the Haitian health system.

Analysis of implementation outcomes of quality improvement initiatives in Haiti: the fingerprint initiative

[ABSTRACT]. Objective. To assess the process and outcomes of the implementation of an electronic fingerprint initiative as part of quality improvement in three health facilities in the Northern Department of Haiti, in terms of its acceptability, adoption, feasibility, fidelity, and sustainability. In Haiti, poor attendance of the healthcare workforce is a nationwide problem, closely related to the quality of care. Three health institutions have tried to implement an electronic fingerprint system to monitor and improve attendance. Methods. An exploratory and qualitative descriptive study of the implementation outcomes of the fingerprint initiative. It was based on semi-structured interviews and one group discussion using purposeful sampling techniques to recruit participants, and an open coding system and deductive approach to analyze the data using ATLAS.ti 8. Results. The fingerprint initiative was successfully implemented in a non-governmental organization supported health facility but, despite some planning, it was never implemented in the public health facilities. The acceptability of the implementation was high in the not-for-profit organization and low in the public settings, mostly in relation to the presence of champions and the leadership at each health facility. Conclusions. We recommend more involvement of the leadership of health facilities in the different phases of the implementation process in order to guarantee acceptability, adoption, fidelity and sustainability. More research is needed to articulate this technology-driven initiative in the Haitian health system.

[RESUMEN]. Objetivo. Evaluar el proceso y los resultados de la puesta en práctica de una iniciativa de digitalización de huellas dactilares como parte de la mejora de la calidad en tres establecimientos de salud del departamento Norte de Haití, en cuanto a su aceptabilidad, adopción, viabilidad, fidelidad y sostenibilidad. En Haití, el absentismo de los trabajadores de atención de salud es un problema nacional, estrechamente relacionado con la calidad de la atención. Tres instituciones de salud han tratado de poner en práctica un sistema de huellas dactilares digitalizadas para monitorear y mejorar la asistencia. Métodos. Se ha llevado a cabo un estudio descriptivo cualitativo y exploratorio de los resultados de la puesta en práctica de la iniciativa de la huella dactilar. Este estudio empleó entrevistas semiestructuradas y una discusión de grupo mediante técnicas de muestreo con fines específicos para reclutar a los participantes, y un sistema de codificación abierta y enfoque deductivo para analizar los datos con ATLAS.ti 8. Resultados. La iniciativa de la huella dactilar se llevó a cabo satisfactoriamente en un establecimiento de salud no gubernamental; sin embargo, a pesar de cierta planificación, no llegó a ponerse en práctica en establecimientos públicos de salud. La aceptabilidad de la implementación fue alta en las organizaciones sin fines de lucro y baja en los entornos públicos, principalmente en lo que respecta a la presencia de líderes y dirigentes en cada establecimiento de salud. Conclusiones. Recomendamos una mayor participación de la gerencia de los establecimientos de salud en las diferentes fases del proceso de ejecución para garantizar aceptabilidad, adopción, fidelidad y sostenibilidad. Se necesita investigación adicional para integrar esta iniciativa impulsada por la tecnología en el sistema de salud haitiano.

[RESUMO]. Objetivo. Avaliar o processo e os resultados da implantação de uma iniciativa de controle de ponto eletrônico por biometria para melhoria da qualidade em três serviços de saúde no Departamento Norte do Haiti quanto à aceitabilidade, adoção, viabilidade, fidelidade e sustentabilidade. A baixa assiduidade no trabalho do pessoal da saúde é um problema em todo o país e está estreitamente relacionada à qualidade da atenção. Foi feita uma tentativa de implantar um sistema de ponto eletrônico por biometria em três instituições de saúde, para monitorar e aumentar a assiduidade no trabalho. Métodos. Estudo exploratório, descritivo e qualitativo dos resultados da implantação da iniciativa de ponto eletrônico por biometria. Os dados foram coletados em entrevistas semiestruturadas e em um grupo de discussão usando técnica de amostragem intencional para recrutar os participantes. A análise de dados foi realizada por codificação aberta e enfoque dedutivo com o uso do software ATLAS.ti 8. Resultados. A iniciativa de ponto eletrônico por biometria foi implantada com êxito em um serviço de saúde apoiado por uma organização não governamental. Porém, apesar do planejamento, ela nunca foi implantada nos serviços da rede pública. A aceitabilidade foi muito boa na entidade sem fins lucrativos, mas foi baixa na rede pública, sobretudo em relação à presença de apoiadores e dirigentes no local. Conclusões. Recomenda-se maior envolvimento dos dirigentes dos serviços de saúde nas diferentes fases do processo de implantação para garantir a aceitabilidade, adoção, fidelidade e sustentabilidade da iniciativa. Mais pesquisas são necessárias para estruturar esta iniciativa com uso de tecnologia no sistema de saúde do Haiti.

In Vivo Antigen Expression Regulates CD4 T Cell Differentiation and Vaccine Efficacy against Mycobacterium tuberculosis Infection.

New vaccines are urgently needed against Mycobacterium tuberculosis (Mtb), which kills more than 1.4 million people each year. CD4 T cell differentiation is a key determinant of protective immunity against Mtb, but it is not fully understood how host-pathogen interactions shape individual antigen-specific T cell populations and their protective capacity. Here, we investigated the immunodominant Mtb antigen, MPT70, which is upregulated in response to gamma interferon (IFN-γ) or nutrient/oxygen deprivation of in vitro-infected macrophages. Using a murine aerosol infection model, we compared the in vivo expression kinetics of MPT70 to a constitutively expressed antigen, ESAT-6, and analyzed their corresponding CD4 T cell phenotype and vaccine protection. For wild-type Mtb, we found that in vivo expression of MPT70 was delayed compared to ESAT-6. This delayed expression was associated with induction of less differentiated MPT70-specific CD4 T cells but, compared to ESAT-6, also reduced protection after vaccination. In contrast, infection with an MPT70-overexpressing Mtb strain promoted highly differentiated KLRG1+CX3CR1+ CD4 T cells with limited lung-homing capacity. Importantly, this differentiated phenotype could be prevented by vaccination, and against the overexpressing strain, vaccination with MPT70 conferred protection similar to vaccination with ESAT-6. Together, our data indicate that high in vivo antigen expression drives T cells toward terminal differentiation and that targeted vaccination with adjuvanted protein can counteract this phenomenon by maintaining T cells in a protective less differentiated state. These observations shed new light on host-pathogen interactions and provide guidance on how future Mtb vaccines can be designed to tip the immune balance in favor of the host.IMPORTANCE Tuberculosis, caused by Mtb, constitutes a global health crisis of massive proportions and the impact of the current coronavirus disease 2019 (COVID-19) pandemic is expected to cause a rise in tuberculosis-related deaths. Improved vaccines are therefore needed more than ever, but a lack of knowledge on protective immunity hampers their development. The present study shows that constitutively expressed antigens with high availability drive highly differentiated CD4 T cells with diminished protective capacity, which could be a survival strategy by Mtb to evade T cell immunity against key antigens. We demonstrate that immunization with such antigens can counteract this phenomenon by maintaining antigen-specific T cells in a state of low differentiation. Future vaccine strategies should therefore explore combinations of multiple highly expressed antigens and we suggest that T cell differentiation could be used as a readily measurable parameter to identify these in both preclinical and clinical studies.

In vivo antigen expression regulates CD4 T cell differentiation and vaccine efficacy against Mycobacterium tuberculosis infection.

New vaccines are urgently needed against Mycobacterium tuberculosis (Mtb), which kills more than 1.4 million people each year. CD4 T cell differentiation is a key determinant of protective immunity against Mtb, but it is not fully understood how host-pathogen interactions shape individual antigen-specific T cell populations and their protective capacity. Here, we investigated the immunodominant Mtb antigen, MPT70, which is upregulated in response to IFN-γ or nutrient/oxygen deprivation of in vitro infected macrophages. Using a murine aerosol infection model, we compared the in vivo expression kinetics of MPT70 to a constitutively expressed antigen, ESAT-6, and analysed their corresponding CD4 T cell phenotype and vaccine-protection. For wild-type Mtb, we found that in vivo expression of MPT70 was delayed compared to ESAT-6. This delayed expression was associated with induction of less differentiated MPT70-specific CD4 T cells but, compared to ESAT-6, also reduced protection after vaccination. In contrast, infection with an MPT70-overexpressing Mtb strain promoted highly differentiated KLRG1+CX3CR1+ CD4 T cells with limited lung-homing capacity. Importantly, this differentiated phenotype could be prevented by vaccination and, against the overexpressing strain, vaccination with MPT70 conferred similar protection as ESAT-6. Together our data indicate that high in vivo antigen expression drives T cells towards terminal differentiation and that targeted vaccination with adjuvanted protein can counteract this phenomenon by maintaining T cells in a protective less-differentiated state. These observations shed new light on host-pathogen interactions and provide guidance on how future Mtb vaccines can be designed to tip the immune-balance in favor of the host.

Interlaboratory bias of albuminuria and proteinuria in hypertensive pregnancy.

BACKGROUND: Measurement of proteinuria in women with hypertensive disorders of pregnancy is of major importance in the diagnosis and management of preeclampsia. Urinary protein/creatinine ratio, which is commonly used to detect kidney damage in preeclampsia, suffers from important analytical limitations, including poor harmonization of results between laboratories. Adoption of albuminuria could help reduce interlaboratory bias, since methods used to quantify it are better harmonized. METHODS: A total of 27 urinary samples collected from hypertensive women evaluated for preeclampsia were sent to four different clinical laboratories in Canada. Urinary proteins and albumin as well as urinary creatinine were measured in duplicates in one batch to calculate protein/creatinine (PCR) and albumin/creatinine (ACR) ratio. Statistical analyses were done to evaluate interlaboratory variability of urinary proteins and urinary albumin. RESULTS: Interlaboratory bias for urinary proteins ranged from 64.7% at low concentration to 3.9% at higher concentrations. In contrast, urinary albumin interlaboratory bias ranged from 29.2% to 4% from low to high concentrations. Coefficient of variation for urinary proteins reached a maximum of 91.5% in lower concentration while urinary albumin highest value was 42.7%. When looking at PCR and ACR ratio, eight samples had PCR measurement range that contained the diagnostic threshold used to detect kidney damage in HDP (30 mg/mmol), while only four samples had ACR ratio measurement range that contained the diagnostic threshold used outside of pregnancy in Canada (2 mg/mmol). CONCLUSION: Interlaboratory bias was lower for urinary albumin measurement compared to urinary proteins in hypertensive women evaluated for preeclampsia. Better harmonization with the use of albumin instead of protein measurement would reduce instances where results of different laboratories lead to opposite diagnosis of kidney damage in pregnancy.

Analysis of implementation outcomes of quality improvement initiatives in Haiti: the fingerprint initiative / Análisis de los resultados de la puesta en práctica de iniciativas para la mejora de la calidad en Haití: la iniciativa de la huella dactilar / Análise dos resultados da implantação de iniciativas para melhoria da qualidade no Haiti: iniciativa de leitura da impressão digital

ABSTRACT Objective. To assess the process and outcomes of the implementation of an electronic fingerprint initiative as part of quality improvement in three health facilities in the Northern Department of Haiti, in terms of its acceptability, adoption, feasibility, fidelity, and sustainability. In Haiti, poor attendance of the healthcare workforce is a nationwide problem, closely related to the quality of care. Three health institutions have tried to implement an electronic fingerprint system to monitor and improve attendance. Methods. An exploratory and qualitative descriptive study of the implementation outcomes of the fingerprint initiative. It was based on semi-structured interviews and one group discussion using purposeful sampling techniques to recruit participants, and an open coding system and deductive approach to analyze the data using ATLAS.ti 8. Results. The fingerprint initiative was successfully implemented in a non-governmental organization supported health facility but, despite some planning, it was never implemented in the public health facilities. The acceptability of the implementation was high in the not-for-profit organization and low in the public settings, mostly in relation to the presence of champions and the leadership at each health facility. Conclusions. We recommend more involvement of the leadership of health facilities in the different phases of the implementation process in order to guarantee acceptability, adoption, fidelity and sustainabiliy. More research is needed to articulate this technology-driven initiative in the Haitian health system.

RESUMEN Objetivo. Evaluar el proceso y los resultados de la puesta en práctica de una iniciativa de digitalización de huellas dactilares como parte de la mejora de la calidad en tres establecimientos de salud del departamento Norte de Haití, en cuanto a su aceptabilidad, adopción, viabilidad, fidelidad y sostenibilidad. En Haití, el absentismo de los trabajadores de atención de salud es un problema nacional, estrechamente relacionado con la calidad de la atención. Tres instituciones de salud han tratado de poner en práctica un sistema de huellas dactilares digitalizadas para monitorear y mejorar la asistencia. Métodos. Se ha llevado a cabo un estudio descriptivo cualitativo y exploratorio de los resultados de la puesta en práctica de la iniciativa de la huella dactilar. Este estudio empleó entrevistas semiestructuradas y una discusión de grupo mediante técnicas de muestreo con fines específicos para reclutar a los participantes, y un sistema de codificación abierta y enfoque deductivo para analizar los datos con ATLAS.ti 8. Resultados. La iniciativa de la huella dactilar se llevó a cabo satisfactoriamente en un establecimiento de salud no gubernamental; sin embargo, a pesar de cierta planificación, no llegó a ponerse en práctica en establecimientos públicos de salud. La aceptabilidad de la implementación fue alta en las organizaciones sin fines de lucro y baja en los entornos públicos, principalmente en lo que respecta a la presencia de líderes y dirigentes en cada establecimiento de salud. Conclusiones. Recomendamos una mayor participación de la gerencia de los establecimientos de salud en las diferentes fases del proceso de ejecución para garantizar aceptabilidad, adopción, fidelidad y sostenibilidad. Se necesita investigación adicional para integrar esta iniciativa impulsada por la tecnología en el sistema de salud haitiano.

RESUMO Objetivo. Avaliar o processo e os resultados da implantação de uma iniciativa de controle de ponto eletrônico por biometria para melhoria da qualidade em três serviços de saúde no Departamento Norte do Haiti quanto à aceitabilidade, adoção, viabilidade, fidelidade e sustentabilidade. A baixa assiduidade no trabalho do pessoal da saúde é um problema em todo o país e está estreitamente relacionada à qualidade da atenção. Foi feita uma tentativa de implantar um sistema de ponto eletrônico por biometria em três instituições de saúde, para monitorar e aumentar a assiduidade no trabalho. Métodos. Estudo exploratório, descritivo e qualitativo dos resultados da implantação da iniciativa de ponto eletrônico por biometria. Os dados foram coletados em entrevistas semiestruturadas e em um grupo de discussão usando técnica de amostragem intencional para recrutar os participantes. A análise de dados foi realizada por codificação aberta e enfoque dedutivo com o uso do software ATLAS.ti 8. Resultados. A iniciativa de ponto eletrônico por biometria foi implantada com êxito em um serviço de saúde apoiado por uma organização não governamental. Porém, apesar do planejamento, ela nunca foi implantada nos serviços da rede pública. A aceitabilidade foi muito boa na entidade sem fins lucrativos, mas foi baixa na rede pública, sobretudo em relação à presença de apoiadores e dirigentes no local. Conclusões. Recomenda-se maior envolvimento dos dirigentes dos serviços de saúde nas diferentes fases do processo de implantação para garantir a aceitabilidade, adoção, fidelidade e sustentabilidade da iniciativa. Mais pesquisas são necessárias para estruturar esta iniciativa com uso de tecnologia no sistema de saúde do Haiti.

Heterologous Production of 1-Tuberculosinyladenosine in Mycobacterium kansasii Models Pathoevolution towards the Transcellular Lifestyle of Mycobacterium tuberculosis.

Mycobacterium kansasii is an environmental nontuberculous mycobacterium that causes opportunistic tuberculosis-like disease. It is one of the most closely related species to the Mycobacterium tuberculosis complex. Using M. kansasii as a proxy for the M. kansasii-M. tuberculosis common ancestor, we asked whether introducing the M. tuberculosis-specific gene pair Rv3377c-Rv3378c into M. kansasii affects the course of experimental infection. Expression of these genes resulted in the production of an adenosine-linked lipid species, known as 1-tuberculosinyladenosine (1-TbAd), but did not alter growth in vitro under standard conditions. Production of 1-TbAd enhanced growth of M. kansasii under acidic conditions through a bacterial cell-intrinsic mechanism independent of controlling pH in the bulk extracellular and intracellular spaces. Production of 1-TbAd led to greater burden of M. kansasii in the lungs of C57BL/6 mice during the first 24 h after infection, and ex vivo infections of alveolar macrophages recapitulated this phenotype within the same time frame. However, in long-term infections, production of 1-TbAd resulted in impaired bacterial survival in both C57BL/6 mice and Ccr2-/- mice. We have demonstrated that M. kansasii is a valid surrogate of M. tuberculosis to study virulence factors acquired by the latter organism, yet shown the challenge inherent to studying the complex evolution of mycobacterial pathogenicity with isolated gene complementation.IMPORTANCE This work sheds light on the role of the lipid 1-tuberculosinyladenosine in the evolution of an environmental ancestor to M. tuberculosis On a larger scale, it reinforces the importance of horizontal gene transfer in bacterial evolution and examines novel models and methods to provide a better understanding of the subtle effects of individual M. tuberculosis-specific virulence factors in infection settings that are relevant to the pathogen.

Patient-Provider Communication and Information, Motivation, and Behavioral Skills in HIV-Positive Adults Initiating Antiretroviral Therapy in Haiti.

While Haiti has scaled up use of antiretroviral therapy (ART), current studies suggest sub-optimal adherence threatens long-term viral suppression in this understudied setting. Patient-provider communication (PPC) and information, motivation, and behavioral skills (IMB) have been implicated in ART adherence globally. However, no studies have examined their relevance in Haiti. The present mixed-methods study utilized cross-sectional survey data from 128 ART-initiating patients at 2 large HIV treatment sites in Haiti, as well as observational data from 12 clinic visits, to document associations between adherence-related PPC and IMB. Multivariate regression analyses suggested that PPC is associated with IMB constructs. At the bivariate level, more effective PPC was associated with higher levels of adherence-related information and motivation, but not behavioral skills. Observational findings indicate infrequent and non-collaborative adherence support. Taken together, findings lay the groundwork for additional research in the area of PPC, IMB, and ART adherence in Haiti.

Immune System Modulations by Products of the Gut Microbiota.

The gut microbiota, which consists of all bacteria, viruses, fungus, and protozoa living in the intestine, and the immune system have co-evolved in a symbiotic relationship since the origin of the immune system. The bacterial community forming the microbiota plays an important role in the regulation of multiple aspects of the immune system. This regulation depends, among other things, on the production of a variety of metabolites by the microbiota. These metabolites range from small molecules to large macro-molecules. All types of immune cells from the host interact with these metabolites resulting in the activation of different pathways, which result in either positive or negative responses. The understanding of these pathways and their modulations will help establish the microbiota as a therapeutic target in the prevention and treatment of a variety of immune-related diseases.

An EMR-Based Alert with Brief Provider-Led ART Adherence Counseling: Promising Results of the InfoPlus Adherence Pilot Study Among Haitian Adults with HIV Initiating ART.

To promote HIV antiretroviral therapy (ART) outcomes in Haiti, we developed a culturally relevant intervention (InfoPlus Adherence) that combines an electronic medical record alert identifying patients at elevated risk of treatment failure and provider-delivered brief problem-solving counseling. We conducted a quasi-experimental mixed-methods study among 146 patients at two large ART clinics in Haiti with 728 historical controls. We conducted quantitative assessments of patients at baseline and intervention completion (6 months) as well as focus groups with health workers and exit interviews with patients. The primary quantitative outcome measures were HIV viral suppression according to medical record and ART adherence in terms of ≥ 90% for "proportion of days covered" (PDC) according to pharmacy dispensing data. Results indicated that the proportion of intervention patients with suppressed VL during the study/historical periods was 80.0%/86.0% and 76.8%/87.4% for controls. In a difference-in-differences (DID) analytic model, the adjusted relative risk for viral suppression with the intervention was 1.15 (95% CI 0.92-1.45, p = 0.21), representing favorable but non-significant association between the intervention and the trajectory of VL outcomes. PDC ≥ 90% during the study/historical periods was 30.9%/11.0% among intervention participants and 16.9%/19.4% among controls. In the adjusted DID model, the relative risk for of PDC ≥ 90% with the intervention was 4.00 (95% CI 1.91-8.38, p < 0.001), representing a highly favorable association between the intervention and the trajectory of PDC outcomes. Qualitative data affirmed acceptability of the intervention, although providers reported some challenges consistently implementing it. Future research is needed to demonstrate efficacy and explore optimal implementation strategies.

Dataset related to the characteristics of the champion that influence the implementation of quality improvement programs in health facilities.

Analyses of the present data are reported in the article "What are the characteristics of the champion that influence the implementation of quality improvement programs?" [5]. Data were collected from April to September 2019 using a qualitative data collection tool, an interview guide (see Appendix 1). A total of 21 staff were interviewed from three different health facilities in the Northern Department of Haiti. They gave their perceptions about the qualities and the characteristics of the champions involved in the planning and implementation of quality improvement initiatives in the health facilities in order to introduce change for a better quality of care. This data article provides an overview of the content of those interviews in terms of the characteristics of the champions. In addition, instructions are included about the output of Atlas ti software. You could reuse those data to get a better understanding of the quality and the characteristics of the champions that play a critical role in the implementation of quality improvement programs. The dataset includes the following: - Raw data: interviews transcripts - The Atlas ti software outputs: codes and quotations - The codebook.

Synthetic mycobacterial molecular patterns partially complete Freund's adjuvant.

Complete Freund's adjuvant (CFA) has historically been one of the most useful tools of immunologists. Essentially comprised of dead mycobacteria and mineral oil, we asked ourselves what is special about the mycobacterial part of this adjuvant, and could it be recapitulated synthetically? Here, we demonstrate the essentiality of N-glycolylated peptidoglycan plus trehalose dimycolate (both unique in mycobacteria) for the complete adjuvant effect using knockouts and chemical complementation. A combination of synthetic N-glycolyl muramyl dipeptide and minimal trehalose dimycolate motif GlcC14C18 was able to upregulate dendritic cell effectors, plus induce experimental autoimmunity qualitatively similar but quantitatively milder compared to CFA. This research outlines how to substitute CFA with a consistent, molecularly-defined adjuvant which may inform the design of immunotherapeutic agents and vaccines benefitting from cell-mediated immunity. We also anticipate using synthetic microbe-associated molecular patterns (MAMPs) to study mycobacterial immunity and immunopathogenesis.