A Machine Learning-Derived Score to Effectively Identify Heart Failure With Preserved Ejection Fraction.

Background: The diagnosis of heart failure with preserved ejection fraction (HFpEF) in the clinical setting remains challenging, especially in patients with obesity. Objectives: This study aimed to identify novel predictors of HFpEF well suited for patients with obesity. Methods: We performed a retrospective analysis of a well-characterized cohort of patients with obesity with HFpEF (n = 404; mean body mass index [BMI] 36.6 kg/m2) and controls (n = 67). We used the machine learning algorithm Gradient Boosting Machine to analyze the association of various parameters with the diagnosis of HFpEF and subsequently created a multivariate logistic model for the diagnosis. Results: Gradient Boosting Machine identified BMI, estimated glomerular filtration rate, left ventricular mass index, and left atrial to left ventricular volume ratio as the strongest predictors of HFpEF. These variables were used to build a model that identified HFpEF with a sensitivity of 0.83, a specificity of 0.82, and an area under the curve (AUC) of 0.88. Internal validation of the model with optimism-adjusted AUC showed an AUC of 0.87. Within the studied cohort, the novel score outperformed the H2FPEF score (AUC: 0.88 vs 0.74; P < 0.001). Conclusions: In a HFpEF cohort with obesity, BMI, estimated glomerular filtration rate, left ventricular mass index, and left atrial to left ventricular volume ratio most correlated with the identification of HFpEF, and a score based on these variables (HFpEF-JH score) outperformed the currently used H2PEF score. Further validation of this novel score is warranted, as it may facilitate improved diagnostic accuracy of HFpEF, particularly in patients with obesity.

B cell-mediated antigen presentation promotes adverse cardiac remodeling in chronic heart failure.

Cardiovascular disease remains the leading cause of death worldwide. A primary driver of cardiovascular mortality is ischemic heart failure, a form of cardiac dysfunction that can develop in patients who survive myocardial infarction. Acute cardiac damage triggers robust changes in the spleen with rapid migration of immune cells from the spleen to the heart. Activating this "cardio-splenic" axis contributes to progressive cardiac dysfunction. The cardio-splenic axis has, therefore, been identified as a promising therapeutic target to prevent or treat heart failure. However, our understanding of the precise mechanisms by which specific immune cells contribute to adverse cardiac remodeling within the cardio-splenic axis remains limited. Here, we show that splenic B cells contribute to the development of heart failure via MHC II-mediated antigen presentation. We found that the adoptive transfer of splenic B cells from mice with ischemic heart failure promoted adverse cardiac remodeling and splenic inflammatory changes in naïve recipient mice. Based on single-cell RNA sequencing analysis of splenic B cells from mice with ischemic heart failure, we hypothesized that B cells contributed to adverse cardiac remodeling through antigen presentation by MHC II molecules. This mechanism was confirmed using transgenic mice with B cell-specific MHC II deletion, and by analyzing circulating B cells from humans who experienced myocardial infarction. Our results broaden our understanding of B lymphocyte biology, reshape current models of immune activation in response to myocardial injury, and point towards MHC II-mediated signaling in B cells as a novel and specific therapeutic target in chronic heart failure.

B cell-mediated antigen presentation promotes adverse cardiac remodeling in chronic heart failure.

Cardiovascular disease remains the leading cause of death worldwide. A primary driver of cardiovascular mortality is ischemic heart failure, a form of cardiac dysfunction that can develop in patients who survive myocardial infarction. Acute cardiac damage triggers robust changes in the spleen with rapid migration of immune cells from the spleen to the heart. Activating this "cardio-splenic" axis contributes to progressive cardiac dysfunction. The cardio-splenic axis has, therefore, been identified as a promising therapeutic target to prevent or treat heart failure. However, our understanding of the precise mechanisms by which specific immune cells contribute to adverse cardiac remodeling within the cardio-splenic axis remains limited. Here, we show that splenic B cells contribute to the development of heart failure via MHC II-mediated antigen presentation. We found that the adoptive transfer of splenic B cells from mice with ischemic heart failure promoted adverse cardiac remodeling and splenic inflammatory changes in naïve recipient mice. Based on single-cell RNA sequencing analysis of splenic B cells from mice with ischemic heart failure, we hypothesized that B cells contributed to adverse cardiac remodeling through antigen presentation by MHC II molecules. This mechanism was confirmed using transgenic mice with B cell-specific MHC II deletion, and by analyzing circulating B cells from humans who experienced myocardial infarction. Our results broaden our understanding of B lymphocyte biology, reshape current models of immune activation in response to myocardial injury, and point towards MHC II-mediated signaling in B cells as a novel and specific therapeutic target in chronic heart failure.

Fatty acid concentrations in preterm infants fed the exclusive human milk diet: a prospective cohort study.

OBJECTIVE: Quantify blood fatty acids and growth outcomes in preterm infants fed the exclusive human milk diet. METHODS: A prospective cohort study of 30 infants 24-34 weeks gestation and ≤1250 g fed the exclusive human milk diet. Blood fatty acids were quantified at two time points. Comparisons were made using two-sample t-tests and Wilcoxon rank sum. RESULTS: Donor human milk-fed (n = 12) compared to mother's own milk-fed infants (n = 18) from birth to after 28 days of life, had an increased interval change of linoleic to docosahexaenoic acid ratio (5.5 vs. -1.1 mole percent ratio, p = 0.034). Docosahexaenoic and eicosapentaenoic acid interval changes were similar between groups. The arachidonic acid change was similar between groups (-2.3 vs. -0.9 mole percent, p = 0.37), however, both experienced a negative change across time. At 36 weeks postmenstrual age, growth velocities were similar for groups. CONCLUSION: An exclusive human milk diet maintains birth docosahexaenoic and eicosapentaenoic acid concentrations. However, the postnatal deficit in arachidonic acid was not prevented.

Serum Proteomic Analysis of Peripartum Cardiomyopathy Reveals Distinctive Dysregulation of Inflammatory and Cholesterol Metabolism Pathways.

BACKGROUND: The pathophysiology of peripartum cardiomyopathy (PPCM) and its distinctive biological features remain incompletely understood. High-throughput serum proteomic profiling, a powerful tool to gain insights into the pathophysiology of diseases at a systems biology level, has never been used to investigate PPCM relative to nonischemic cardiomyopathy. OBJECTIVES: The aim of this study was to characterize the pathophysiology of PPCM through serum proteomic analysis. METHODS: Aptamer-based proteomic analysis (SomaScan 7K) was performed on serum samples from women with PPCM (n = 67), women with nonischemic nonperipartum cardiomyopathy (NPCM) (n = 31), and age-matched healthy peripartum and nonperipartum women (n = 10 each). Serum samples were obtained from the IPAC (Investigation of Pregnancy-Associated Cardiomyopathy) and IMAC2 (Intervention in Myocarditis and Acute Cardiomyopathy) studies. RESULTS: Principal component analysis revealed unique clustering of each patient group (P for difference <0.001). Biological pathway analyses of differentially measured proteins in PPCM relative to NPCM, before and after normalization to pertinent healthy controls, highlighted specific dysregulation of inflammatory pathways in PPCM, including the upregulation of the cholesterol metabolism-related anti-inflammatory pathway liver-X receptor/retinoid-X receptor (LXR/RXR) (P < 0.01, Z-score 1.9-2.1). Cardiac recovery by 12 months in PPCM was associated with the downregulation of pro-inflammatory pathways and the upregulation of LXR/RXR, and an additional RXR-dependent pathway involved in the regulation of inflammation and metabolism, peroxisome proliferator-activated receptor α/RXRα signaling. CONCLUSIONS: Serum proteomic profiling of PPCM relative to NPCM and healthy controls indicated that PPCM is a distinct disease entity characterized by the unique dysregulation of inflammation-related pathways and cholesterol metabolism-related anti-inflammatory pathways. These findings provide insight into the pathophysiology of PPCM and point to novel potential therapeutic targets.

Myocardial Immune Cells: The Basis of Cardiac Immunology.

The mammalian heart is characterized by the presence of striated myocytes, which allow continuous rhythmic contraction from early embryonic development until the last moments of life. However, the myocardium contains a significant contingent of leukocytes from every major class. This leukocyte pool includes both resident and nonresident immune cells. Over recent decades, it has become increasingly apparent that the heart is intimately sensitive to immune signaling and that myocardial leukocytes exhibit an array of critical functions, both in homeostasis and in the context of cardiac adaptation to injury. Here, we systematically review current knowledge of all major leukocyte classes in the heart, discussing their functions in health and disease. We also highlight the connection between the myocardium, immune cells, lymphoid organs, and both local and systemic immune responses.

Fecal Elastase in Preterm Infants to Predict Growth Outcomes.

OBJECTIVES: Preterm infants are born functionally pancreatic insufficient with decreased pancreatic production of lipase and proteases. Developmental pancreatic insufficiency (PI) may contribute to reduced nutrient absorption and growth failure. We sought to determine longitudinal fecal elastase (ELA1) levels in a cohort of preterm infants and whether levels are associated with growth outcomes. METHODS: Prospective observational study of 30 infants 24-34 weeks gestational age and birth weight ≤1250 g fed the exclusive human milk diet, consisting of human milk with human milk-based fortifier. ELA1 was quantified by ELISA during the first 2 weeks of life [Early; 7.5 ± 1.8 days of life (DOL)] and after attainment of full, fortified feedings (Late; 63.6 ± 24.1 DOL). RESULTS: Early ELA1 levels were 192.2 ± 96.4 µg/g, and Late ELA1 levels were 268.0 ± 80.3 µg/g, 39.4% higher (P = 0.01). Infants with early PI (ELA1 < 200 µg/g) were more likely male and of lower gestational age, weight, length, and head circumference at birth. These variables, but not PI status, independently predicted somatic growth. CONCLUSIONS: Fecal ELA1 in preterm infants fed exclusive human milk diet increases with postnatal age. Although pancreatic function in preterm infants may serve as a biological contributor to early postnatal growth failure, additional studies using fecal ELA1 as a predictive biomarker for growth failure are needed in larger cohorts.

Quality Improvement to Promote Sepsis Reassessment: The Sepsis Reassessment Protocol Improvement Project (SRPIP).

BACKGROUND: Implementation of the Surviving Sepsis Campaign (SSC) guidelines into practice has demonstrated improved outcomes. LOCAL PROBLEM: Compliance with a sepsis protocol, based on the SSC guidelines, in an urban teaching hospital was below the national average. METHODS: A pre- and posttest intervention design was used to improve clinician knowledge, confidence, and compliance with the protocol. INTERVENTIONS: Educational modules were developed on the SSC guidelines and reminder system alerts (RSA) for timely revaluation of patients with sepsis and lactate monitoring were implemented. RESULTS: A total of 33 (48%) clinicians participated. There was an increase in knowledge, documentation of sepsis reassessment, and serum lactate monitoring. There was an improvement in clinician perceptions following the initiative. CONCLUSIONS: The results demonstrate that education, combined with RSAs, can improve protocol knowledge and compliance.

COVID-19 and Myocarditis: Review of Clinical Presentations, Pathogenesis and Management.

There are four main myocarditis presentations identified in the context of severe acute respiratory coronavirus 2 (SARS-CoV-2): myocarditis associated with acute coronavirus disease 2019 (COVID-19) infection, post-acute COVID-19 syndrome, multisystem inflammatory syndrome, and vaccination-associated myocarditis. This article reviews the clinical features and current management strategies for each of these presentations. The overall prevalence of myocarditis is considered to be rare, although accurate estimation is affected by heterogeneity in diagnostic criteria and reporting, as well as infrequent use of gold-standard diagnostic endomyocardial biopsy. Severity of disease can range from mild symptoms to fulminant myocarditis. Therapeutic interventions are typically supportive and extrapolated from treatment for non-COVID-19 viral myocarditis. Several pathogenic mechanisms for the development of myocarditis have been proposed, and ongoing research is critical for elucidating disease pathogenesis and potentially identifying therapeutic targets. The long-term cardiovascular sequelae of SARS-CoV-2 infections and associated myocarditis require further elucidation and understanding.

Development of a veterinary emergency open standard competency framework using a competency-based model of medical education.

OBJECTIVE: To address the shortage of emergency veterinarians, the profession is exploring accelerated training pathways. We sought to contribute to the solution by developing the foundation for an open standard, competency-based veterinary emergency training curriculum for use by any program. We also developed a curricular delivery, tracking, and assessment system to demonstrate how the framework can be integrated into training programs.  DESIGN: Hybrid Delphi method.  SETTING: Academia and referral practice.  ANIMALS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An emergency veterinary competency framework was developed by adapting the human Model of the Clinical Practice of Emergency Medicine, which aligns with the Competency-Based Veterinary Education framework, to produce 4 areas of core competency: Patient Care, Interpersonal/Communication, Professionalism, and Practice-based Learning/Improvement. A comprehensive list of veterinary emergency skills was generated and organized within the framework utilizing the hybrid Delphi method. An initial survey completed by 133 emergency and critical care specialists and emergency room clinicians produced data regarding the value of specific skills. An 11-member focus group consisting of survey participants iterated upon the survey results to produce a master library of skills and cases, including 56 Patient Care, 43 Interpersonal/Communication, 11 Practice-based Learning/Improvement, and 20 Professionalism skills, as well as 155 case types. The curricular delivery system tracks and assesses case management proficiency and development of knowledge and professional skills using a patient care eLearning program and simulation training environment.  CONCLUSIONS: The increasing need for emergency veterinarians is a shared industry-wide challenge. To contribute toward a collective solution, we have undergone an evidence-based process to create the foundation for an open standard competency framework composed of a library of skills and cases. We offer this open standard framework to the veterinary profession and hope it continues to grow and evolve as we drive toward developing competency-based training programs that address the shortage of emergency veterinarians.

Pulmonary Manifestations of GATA2 Deficiency.

BACKGROUND: GATA2 deficiency is a genetic disorder of hematopoiesis, lymphatics, and immunity caused by autosomal dominant or sporadic mutations in GATA2. The disease has a broad phenotype encompassing immunodeficiency, myelodysplasia, leukemia, and vascular or lymphatic dysfunction as well as prominent pulmonary manifestations. RESEARCH QUESTION: What are the pulmonary manifestations of GATA2 deficiency? STUDY DESIGN AND METHODS: A retrospective review was conducted of clinical medical records, diagnostic imaging, pulmonary pathologic specimens, and tests of pulmonary function. RESULTS: Of 124 patients (95 probands and 29 ascertained), the lung was affected in 56%. In addition to chronic infections, pulmonary alveolar proteinosis (11 probands) and pulmonary arterial hypertension (nine probands) were present. Thoracic CT imaging found small nodules in 54% (54 probands and 12 relatives), reticular infiltrates in 40% (45 probands and four relatives), paraseptal emphysema in 25% (30 probands and one relative), ground-glass opacities in 35% (41 probands and two relatives), consolidation in 21% (23 probands and two relatives), and a typical crazy-paving pattern in 7% (eight probands and no relatives). Nontuberculous mycobacteria were the most frequent organisms associated with chronic infection. Allogeneic hematopoietic stem cell transplantation successfully reversed myelodysplasia and immune deficiency and also improved pulmonary hypertension and pulmonary alveolar proteinosis in most patients. INTERPRETATION: GATA2 deficiency has prominent pulmonary manifestations. These clinical observations confirm the essential role of hematopoietic cells in many aspects of pulmonary function, including infections, alveolar proteinosis, and pulmonary hypertension, many of which precede the formal diagnosis, and many of which respond to stem cell transplantation.

Structural basis for the complex DNA binding behavior of the plant stem cell regulator WUSCHEL.

Stem cells are one of the foundational evolutionary novelties that allowed the independent emergence of multicellularity in the plant and animal lineages. In plants, the homeodomain (HD) transcription factor WUSCHEL (WUS) is essential for the maintenance of stem cells in the shoot apical meristem. WUS has been reported to bind to diverse DNA motifs and to act as transcriptional activator and repressor. However, the mechanisms underlying this remarkable behavior have remained unclear. Here, we quantitatively delineate WUS binding to three divergent DNA motifs and resolve the relevant structural underpinnings. We show that WUS exhibits a strong binding preference for TGAA repeat sequences, while retaining the ability to weakly bind to TAAT elements. This behavior is attributable to the formation of dimers through interactions of specific residues in the HD that stabilize WUS DNA interaction. Our results provide a mechanistic basis for dissecting WUS dependent regulatory networks in plant stem cell control.

MicroRNA-21 ablation exacerbates aldosterone-mediated cardiac injury, remodeling, and dysfunction.

Primary aldosteronism is characterized by excess aldosterone secretion by the adrenal gland independent of the renin-angiotensin system and accounts for ~10% of hypertensive patients. Excess aldosterone causes cardiac hypertrophy, fibrosis, inflammation, and hypertension. The molecular mechanisms that trigger the onset and progression of aldosterone-mediated cardiac injury remain incompletely understood. MicroRNAs (miRNAs) are endogenous, small, noncoding RNAs that have been implicated in multiple cardiac pathologies; however, their regulation and role in aldosterone-mediated cardiac injury and dysfunction remains mostly unknown. We previously reported that microRNA-21 (miR-21) is the most upregulated miRNA by excess aldosterone in the left ventricle in a rat experimental model of primary aldosteronism. To elucidate the role of miR-21 in aldosterone-mediated cardiac injury and dysfunction, miR-21 knockout mice and their wild-type littermates were treated with aldosterone infusion and salt in the drinking water for 2 or 8 wk. miR-21 genetic ablation exacerbated aldosterone/salt-mediated cardiac hypertrophy and cardiomyocyte cross-sectional area. Furthermore, miR-21 genetic ablation increased the cardiac expression of fibrosis and inflammation markers and fetal gene program. miR-21 genetic ablation increased aldosterone/salt-mediated cardiac dysfunction but did not affect aldosterone/salt-mediated hypertension. miR-21 target gene Sprouty 2 may be implicated in the cardiac effects of miR-21 genetic ablation. Our study shows that miR-21 genetic ablation exacerbates aldosterone/salt-mediated cardiac hypertrophy, injury, and dysfunction blood pressure independently. These results suggest that miR-21 plays a protective role in the cardiac pathology triggered by excess aldosterone. Furthermore, miR-21 supplementation may be a novel therapeutic approach to abolish or mitigate excess aldosterone-mediated cardiovascular deleterious effects in primary aldosteronism.

Loss of CaMKI Function Disrupts Salt Aversive Learning in C. elegans.

The ability to adapt behavior to environmental fluctuations is critical for survival of organisms ranging from invertebrates to mammals. Caenorhabditis elegans can learn to avoid sodium chloride when it is paired with starvation. This behavior may help animals avoid areas without food. Although some genes have been implicated in this salt-aversive learning behavior, critical genetic components, and the neural circuit in which they act, remain elusive. Here, we show that the sole worm ortholog of mammalian CaMKI/IV, CMK-1, is essential for salt-aversive learning behavior in C. elegans hermaphrodites. We find that CMK-1 acts in the primary salt-sensing ASE neurons to regulate this behavior. By characterizing the intracellular calcium dynamics in ASE neurons using microfluidics, we find that loss of cmk-1 has subtle effects on sensory-evoked calcium responses in ASE axons and their modulation by salt conditioning. Our study implicates the expression of the conserved CaMKI/CMK-1 in chemosensory neurons as a regulator of behavioral plasticity to environmental salt in C. elegansSIGNIFICANCE STATEMENT Like other animals, the nematode Caenorhabditis elegans depends on salt for survival and navigates toward high concentrations of this essential mineral. In addition to its role as an essential nutrient, salt also causes osmotic stress at high concentrations. A growing body of evidence indicates that C. elegans balances the requirement for salt with the danger it presents through a process called salt-aversive learning. We show that this behavior depends on expression of a calcium/calmodulin-dependent kinase, CMK-1, in the ASE salt-sensing neurons. Our study identifies CMK-1 and salt-sensitive chemosensory neurons as key factors in this form of behavioral plasticity.

Control of plant cell fate transitions by transcriptional and hormonal signals.

Plant meristems carry pools of continuously active stem cells, whose activity is controlled by developmental and environmental signals. After stem cell division, daughter cells that exit the stem cell domain acquire transit amplifying cell identity before they are incorporated into organs and differentiate. In this study, we used an integrated approach to elucidate the role of HECATE (HEC) genes in regulating developmental trajectories of shoot stem cells in Arabidopsis thaliana. Our work reveals that HEC function stabilizes cell fate in distinct zones of the shoot meristem thereby controlling the spatio-temporal dynamics of stem cell differentiation. Importantly, this activity is concomitant with the local modulation of cellular responses to cytokinin and auxin, two key phytohormones regulating cell behaviour. Mechanistically, we show that HEC factors transcriptionally control and physically interact with MONOPTEROS (MP), a key regulator of auxin signalling, and modulate the autocatalytic stabilization of auxin signalling output.

MicroRNA-21: Expression in oligodendrocytes and correlation with low myelin mRNAs in depression and alcoholism.

MiR-21 is a microRNA implicated in cancer, development, and cardiovascular diseases and expressed in the central nervous system (CNS), especially after injury. However, the cellular expression of miR-21 in the adult CNS has not been clearly established either in mice or human subjects, while its alteration in psychiatric disorders is unknown. MiR-21 expression was characterized in reporter mice expressing ß-galactosidase (LacZ) under the endogenous miR-21 promoter (miR-21/LacZ). Brain co-localization of miR-21/LacZ with specific neural markers was examined by double immunofluorescence in reporter mice, while extent of immunostaining for myelin basic protein and PDGFRα was determined in miR-21 knockout and wild-type mice. Levels of miR-21, and mRNAs of selected miR-21 targets, miR-21 regulator STAT3 and myelin-related proteins were measured by qRT-PCR in the white matter (WM) adjacent to the left postmortem orbitofrontal cortex (OFC) of human subjects with major depressive disorder (MDD), alcoholism, comorbid MDD plus alcoholism (MDA) and non-psychiatric control subjects. MiR-21/LacZ was highly expressed in cell bodies of WM and myelinated portions of gray matter (GM). Labeled cell bodies were identified as oligodendrocytes, while miR-21/LacZ was barely detectable in other cell types. MiR-21, as well as the mRNAs of several myelin-related proteins, were reduced in the WM of subjects with MDD and alcoholism. MiR-21 positively correlated with mRNA of myelin-related proteins and astrocytic GFAP. High expression of miR-21 in adult oligodendrocytes and the correlation of miR-21 decrease with mRNA of some myelin proteins, regulator STAT3, and oligodendrocyte-related transcription factors suggest an involvement of miR-21 in WM alterations in depression and alcoholism.

Role and Regulation of MicroRNAs in Aldosterone-Mediated Cardiac Injury and Dysfunction in Male Rats.

Primary aldosteronism is characterized by excess aldosterone (ALDO) secretion independent of the renin-angiotensin system and accounts for approximately 10% of hypertension cases. Excess ALDO that is inappropriate for salt intake status causes cardiac hypertrophy, inflammation, fibrosis, and hypertension. The molecular mechanisms that trigger the onset and progression of ALDO-mediated cardiac injury are poorly understood. MicroRNAs (miRNAs) are endogenous, small, noncoding RNAs that have been implicated in diverse cardiac abnormalities, yet very little is known about their regulation and role in ALDO-mediated cardiac injury. To elucidate the regulation of miRNAs in ALDO-mediated cardiac injury, we performed a time-series analysis of left ventricle (LV) miRNA expression. Uninephrectomized male Sprague-Dawley rats were treated with ALDO (0.75 µg/h) infusion and SALT (1.0% NaCl/0.3% KCl) in the drinking water for up to 8 weeks. ALDO/SALT time dependently modulated the expression of multiple miRNAs in the LV. miR-21 was the most upregulated miRNA after 2 weeks of treatment and remained elevated until the end of the study. To elucidate the role of miR-21 in ALDO/SALT-mediated cardiac injury, miR-21 was downregulated by using antagomirs in ALDO/SALT-treated rats. miR-21 downregulation exacerbated ALDO/SALT-mediated cardiac hypertrophy, expression of fibrosis marker genes, interstitial and perivascular fibrosis, OH-proline content, and cardiac dysfunction. These results suggest that ALDO/SALT-mediated cardiac miR-21 upregulation may be a compensatory mechanism that mitigates ALDO/SALT-mediated cardiac deleterious effects. We speculate that miR-21 supplementation would have beneficial effects in reverting or mitigating cardiac injury and dysfunction in patients with primary aldosteronism.

CO2 reduction over NaNbO3 and NaTaO3 perovskite photocatalysts.

The activity of NaNbO3 and NaTaO3 perovskites for the photocatalytic reduction of CO2 is studied in this work. For this purpose, sodium niobate and tantalate have been prepared using solid-state reactions, extensively characterised by means of powder X-ray diffraction, UV-vis, photoluminescence and Raman spectroscopies and N2 adsorption isotherms, and tested in the gas-phase reduction of CO2 under UV light in a continuous flow photoreactor. NaNbO3 is constituted of an orthorhombically distorted perovskite structure, while a ca. 4.5 : 1 combination of the orthorhombic and monoclinic modifications is found in the tantalate. Both catalysts exhibit interesting intrinsic activities, with the tantalate material giving rise to a slightly higher performance. This is attributed to a compromise situation between electron-hole recombination and the reducing potential of conduction band electrons. In addition, a decrease in the competition of water protons for photogenerated electrons is observed with both catalysts with respect to TiO2.

Mediastinal and Disseminated Mycobacterium kansasii Disease in GATA2 Deficiency.

RATIONALE: Mycobacterium kansasii usually causes chronic pulmonary infections in immunocompetent patients. In contrast, disseminated M. kansasii disease is commonly associated with advanced human immunodeficiency virus infection, but is reported infrequently in other immunocompromised patients. OBJECTIVES: To identify common clinical manifestations and potential risk factors for M. kansasii infection in patients with GATA2 deficiency. METHODS: We reviewed M. kansasii disease associated with GATA2 deficiency at one institution and disease associated with primary and other immunodeficiencies reported in the literature. MEASUREMENTS AND MAIN RESULTS: Nine patients with GATA2 deficiency developed M. kansasii infections. Six patients developed disseminated disease. All patients presented with significant mediastinal lymphadenopathy or abscesses. Seven patients had pulmonary risk factors, including six smokers. The majority of patients had low numbers of neutrophils, monocytes, B cells, CD4+ T cells, and natural killer cells. Other conditions associated with disseminated M. kansasii disease were thymic disorders and IFN-γ/IL-12 defects. CONCLUSIONS: Disseminated M. kansasii disease involving mediastinal lymph nodes is surprisingly common in GATA2 deficiency, but also occurs in defects of IFN-γ synthesis and response. Disseminated M. kansasii should be considered a marker indicating a need to evaluate for immunodeficiency syndromes.