Planktonic microbial signatures of sinking particle export in the open ocean's interior.

A considerable amount of particulate carbon produced by oceanic photosynthesis is exported to the deep-sea by the "gravitational pump" (~6.8 to 7.7 Pg C/year), sequestering it from the atmosphere for centuries. How particulate organic carbon (POC) is transformed during export to the deep sea however is not well understood. Here, we report that dominant suspended prokaryotes also found in sinking particles serve as informative tracers of particle export processes. In a three-year time series from oceanographic campaigns in the Pacific Ocean, upper water column relative abundances of suspended prokaryotes entrained in sinking particles decreased exponentially from depths of 75 to 250 m, conforming to known depth-attenuation patterns of carbon, energy, and mass fluxes in the epipelagic zone. Below ~250 m however, the relative abundance of suspended prokaryotes entrained in sinking particles increased with depth. These results indicate that microbial entrainment, colonization, and sinking particle formation are elevated at mesopelagic and bathypelagic depths. Comparison of suspended and sinking particle-associated microbes provides information about the depth-variability of POC export and biotic processes, that is not evident from biogeochemical data alone.

Marine viral particles reveal an expansive repertoire of phage-parasitizing mobile elements.

Phage satellites are mobile genetic elements that propagate by parasitizing bacteriophage replication. We report here the discovery of abundant and diverse phage satellites that were packaged as concatemeric repeats within naturally occurring bacteriophage particles in seawater. These same phage-parasitizing mobile elements were found integrated in the genomes of dominant co-occurring bacterioplankton species. Like known phage satellites, many marine phage satellites encoded genes for integration, DNA replication, phage interference, and capsid assembly. Many also contained distinctive gene suites indicative of unique virus hijacking, phage immunity, and mobilization mechanisms. Marine phage satellite sequences were widespread in local and global oceanic virioplankton populations, reflecting their ubiquity, abundance, and temporal persistence in marine planktonic communities worldwide. Their gene content and putative life cycles suggest they may impact host-cell phage immunity and defense, lateral gene transfer, bacteriophage-induced cell mortality and cellular host and virus productivity. Given that marine phage satellites cannot be distinguished from bona fide viral particles via commonly used microscopic techniques, their predicted numbers (∼3.2 × 1026 in the ocean) may influence current estimates of virus densities, production, and virus-induced mortality. In total, the data suggest that marine phage satellites have potential to significantly impact the ecology and evolution of bacteria and their viruses throughout the oceans. We predict that any habitat that harbors bacteriophage will also harbor similar phage satellites, making them a ubiquitous feature of most microbiomes on Earth.

Diverse Genomic Traits Differentiate Sinking-Particle-Associated versus Free-Living Microbes throughout the Oligotrophic Open Ocean Water Column.

Bacteria and archaea are central to the production, consumption, and remineralization of dissolved and particulate organic matter and contribute critically to carbon delivery, nutrient availability, and energy transformations in the deep ocean. To explore environmentally relevant genomic traits of sinking-particle-associated versus free-living microbes, we compared habitat-specific metagenome-assembled genomes recovered throughout the water column in the North Pacific Subtropical Gyre. The genomic traits of sinking-particle-associated versus free-living prokaryotes were compositionally, functionally, and phylogenetically distinct. Substrate-specific transporters and extracellular peptidases and carbohydrate-active enzymes were more enriched and diverse in particle-associated microbes at all depths than in free-living counterparts. These data indicate specific roles for particle-attached microbes in particle substrate hydrolysis, uptake, and remineralization. Shallow-water particle-associated microbes had elevated genomic GC content and proteome nitrogen content and reduced proteome carbon content in comparison to abyssal particle-associated microbes. An inverse trend was observed for their sympatric free-living counterparts. These different properties of attached microbes are postulated to arise in part due to elevated organic and inorganic nitrogen availability inside sinking particles. Particle-attached microbes also were enriched in genes for environmental sensing via two-component regulatory systems, and cell-cell interactions via extracellular secretion systems, reflecting their surface-adapted lifestyles. Finally, particle-attached bacteria had greater predicted maximal growth efficiencies than free-living bacterioplankton at all depths. All of these particle-associated specific genomic and proteomic features appear to be driven by microhabitat-specific elevated nutrient and energy availability as well as surface-associated competitive and synergistic ecological interactions. Although some of these characteristics have been previously postulated or observed individually, we report them together here in aggregate via direct comparisons of cooccurring free-living and sinking-particle-attached microbial genomes from the open ocean. IMPORTANCE Particle-attached microbes play large roles in the ocean carbon cycle and help to sequester atmospheric CO2 and to deliver nutrients and energy on sinking particles to the deep sea. Here, we report on the genomic traits of particle-attached versus free-living microbes throughout the ocean water column to better differentiate their specific metabolic and ecological roles in the sea. In general, the genomic properties and contents of particle-attached microbes reflected the physical and chemical compositions of their environment as well as their microhabitat-specific adaptive traits. In comparison to cooccurring free-living microbes, particle-attached microbes had larger genomes, greater capacity for extracellular polymer degradation, greater environmental sensing and response capacity, greater potential for motility and attachment, and higher growth efficiencies. Our results present an integrated new perspective on sinking-particle-attached microbial adaptive traits that contribute to their critical ecological and biogeochemical roles and activities in the sea.

Multi-Omics Profiling Specifies Involvement of Alternative Ribosomal Proteins in Response to Zinc Limitation in Mycobacterium smegmatis.

Zinc ion (Zn2+) is an essential micronutrient and a potent antioxidant. However, Zn2+ is often limited in the environment. Upon Zn2+ limitation, Mycolicibacterium (basonym: Mycobacterium) smegmatis (Msm) undergoes a morphogenesis, which relies on alternative ribosomal proteins (AltRPs); i.e., Zn2+-independent paralogues of Zn2+-dependent ribosomal proteins. However, the underlying physiological changes triggered by Zn2+ limitation and how AltRPs contribute to these changes were not known. In this study, we expand the knowledge of mechanisms utilized by Msm to endure Zn2+ limitation, by comparing the transcriptomes and proteomes of Zn2+-limited and Zn2+-replete Msm. We further compare, corroborate and contrast our results to those reported for the pathogenic mycobacterium, M. tuberculosis, which highlighted conservation of the upregulated oxidative stress response when Zn2+ is limited in both mycobacteria. By comparing the multi-omics analysis of a knockout mutant lacking AltRPs (ΔaltRP) to the Msm wild type strain, we specify the involvement of AltRPs in the response to Zn2+ limitation. Our results show that AltRP expression in Msm does not affect the conserved oxidative stress response during Zn2+ limitation observed in mycobacteria, but AltRPs do significantly impact expression patterns of numerous genes that may be involved in morphogenesis or other adaptive responses. We conclude that AltRPs are not only important as functional replacements for their Zn2+-dependent paralogues; they are also involved in the transcriptomic response to the Zn2+-limited environment.

Zinc limitation triggers anticipatory adaptations in Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) has complex and dynamic interactions with the human host, and subpopulations of Mtb that emerge during infection can influence disease outcomes. This study implicates zinc ion (Zn2+) availability as a likely driver of bacterial phenotypic heterogeneity in vivo. Zn2+ sequestration is part of "nutritional immunity", where the immune system limits micronutrients to control pathogen growth, but this defense mechanism seems to be ineffective in controlling Mtb infection. Nonetheless, Zn2+-limitation is an environmental cue sensed by Mtb, as calprotectin triggers the zinc uptake regulator (Zur) regulon response in vitro and co-localizes with Zn2+-limited Mtb in vivo. Prolonged Zn2+ limitation leads to numerous physiological changes in vitro, including differential expression of certain antigens, alterations in lipid metabolism and distinct cell surface morphology. Furthermore, Mtb enduring limited Zn2+ employ defensive measures to fight oxidative stress, by increasing expression of proteins involved in DNA repair and antioxidant activity, including well described virulence factors KatG and AhpC, along with altered utilization of redox cofactors. Here, we propose a model in which prolonged Zn2+ limitation defines a population of Mtb with anticipatory adaptations against impending immune attack, based on the evidence that Zn2+-limited Mtb are more resistant to oxidative stress and exhibit increased survival and induce more severe pulmonary granulomas in mice. Considering that extracellular Mtb may transit through the Zn2+-limited caseum before infecting naïve immune cells or upon host-to-host transmission, the resulting phenotypic heterogeneity driven by varied Zn2+ availability likely plays a key role during early interactions with host cells.

Black-white disparities in 2009 H1N1 vaccination among adults in the United States: A cautionary tale for the COVID-19 pandemic.

BACKGROUND: Prior research has highlighted racial and ethnic disparities in H1N1 vaccination in the United States. Our study adds to this literature by utilizing an intersectionality framework to examine the joint influence of race and sex on H1N1 vaccination beliefs and behaviors among non-Hispanic blacks and non-Hispanic whites (hereafter blacks and whites). METHODS: Using data from the National H1N1 Flu Survey of U.S. adults, we measured differences in beliefs about the safety and efficacy of the H1N1 vaccine among black women, black men, white women, and white men. We then estimated a series of nested logistic regression models to examine how race/sex vaccination disparities were influenced by health beliefs, socioeconomic status (SES), pre-existing conditions, and healthcare. RESULTS: Black respondents were more likely than white respondents to express reservations about the safety and efficacy of the H1N1 vaccine. Consistent with those beliefs, white females reported the highest rate of H1N1 vaccination (28.4%), followed by white males (26.3%), black males (21.6%), and black females (17.5%). Differences in health beliefs, SES, pre-existing conditions, and healthcare explained lower odds of H1N1 vaccination among white men and black men, relative to white women. However, black women experienced 35-45% lower odds of vaccination than white women across all models, highlighting the intersectional nature of these associations. DISCUSSION: The 2009 H1N1 influenza pandemic provides a cautionary tale about the distribution of new vaccines across large populations with diverse racial, sex, and socioeconomic characteristics. Despite differences between the H1N1 and COVID-19 pandemics, our study warns that many black Americans will forego COVID-19 vaccines unless swift action is taken to address black-white disparities in access to vital resources. Public health stakeholders can also encourage widespread adoption of COVID-19 vaccines by tailoring health promotion messages for different groups of racial minorities, especially groups like black women who face intersecting disadvantages.

Assembly-free single-molecule sequencing recovers complete virus genomes from natural microbial communities.

Viruses are the most abundant biological entities on Earth and play key roles in host ecology, evolution, and horizontal gene transfer. Despite recent progress in viral metagenomics, the inherent genetic complexity of virus populations still poses technical difficulties for recovering complete virus genomes from natural assemblages. To address these challenges, we developed an assembly-free, single-molecule nanopore sequencing approach, enabling direct recovery of complete virus genome sequences from environmental samples. Our method yielded thousands of full-length, high-quality draft virus genome sequences that were not recovered using standard short-read assembly approaches. Additionally, our analyses discriminated between populations whose genomes had identical direct terminal repeats versus those with circularly permuted repeats at their termini, thus providing new insight into native virus reproduction and genome packaging. Novel DNA sequences were discovered, whose repeat structures, gene contents, and concatemer lengths suggest they are phage-inducible chromosomal islands, which are packaged as concatemers in phage particles, with lengths that match the size ranges of co-occurring phage genomes. Our new virus sequencing strategy can provide previously unavailable information about the genome structures, population biology, and ecology of naturally occurring viruses and viral parasites.

Hemodynamics of the diastolic pressure gradients in acute heart failure: implications for the diagnosis of pre-capillary pulmonary hypertension in left heart disease.

The diastolic pressure gradient (DPG) has been proposed as the metric of choice for the diagnosis of pulmonary vascular changes in left heart disease. We tested the hypothesis that this metric is less sensitive to changes in left atrial pressure and stroke volume (SV) than the transpulmonary gradient (TPG). We studied the effect of dynamic changes in pulmonary capillary wedge pressure (PCWP), SV, and pulmonary artery capacitance (PAC) on DPG and TPG in 242 patients with acute heart failure undergoing decongestive therapy with continuous hemodynamic monitoring. There was a close impact of PCWP reduction on TPG and DPG, with a 0.13 mmHg (95% confidence interval [CI] 0.07-0.19, P < 0.0001) and 0.21 mmHg (95% CI 0.16-0.25, P < 0.0001) increase for every 1 mmHg decrease in PCWP, respectively. Changes in SV had a negligible effect on TPG and DPG (0.19 and 0.13 mmHg increase, respectively, for every 10-mL increase in SV). Heart rate was positively associated with DPG (0.41-mmHg increase per 10 BPM [95% CI 0.22-0.60, P < 0.0001]). The resistance-compliance product was positively associated with both TPG and DPG (2.65 mmHg [95% CI 2.47-2.83] and 1.94 mmHg [95% CI 1.80-2.08] for each 0.1-s increase, respectively). In conclusion, DPG is not less sensitive to changes in left atrial pressure and SV compared with TPG. Although DPG was not affected by changes in PAC, the concomitant increase in the resistance-compliance product increases DPG.

The Influence of Hispanic Ethnicity and Nativity Status on 2009 H1N1 Pandemic Vaccination Uptake in the United States.

Previous research suggests Hispanic vaccination rates for H1N1 were similar to non-Hispanic whites. These previous estimates do not take into account nativity status. Using the 2010 National Health Interview Survey, we estimate adult H1N1 vaccination rates for non-Hispanic whites (n = 8780), U.S.-born Hispanics (n = 1142), and foreign-born Hispanics (n = 1912). To test Fundamental Cause Theory, we estimate odds of H1N1 vaccination while controlling for flexible resources (e.g., educational and economic capital), ethnicity, and nativity status. Foreign-born Hispanics experienced the lowest rates of H1N1 vaccination (15%), followed by U.S.-born Hispanics (18%) and non-Hispanic whites (21%). Regression models show odds of H1N1 vaccination did not differ among these three groups after controlling for sociodemographic characteristics. Insufficient access to flexible resources and healthcare coverage among foreign-born Hispanics was responsible for relatively low rates of H1N1 vaccination. Addressing resource disparities among Hispanics could increase vaccination uptake in the future, reducing inequities in disease burden.

Mutation of the toxR or mshA genes from Vibrio coralliilyticus strain OCN014 reduces infection of the coral Acropora cytherea.

Thermal stress increases the incidence of coral disease, which is predicted to become more common with climate change, even on pristine reefs such as those surrounding Palmyra Atoll in the Northern Line Islands that experience minimal anthropogenic stress. Here we describe a strain of Vibrio coralliilyticus, OCN014, which was isolated from Acropora cytherea during an outbreak of Acropora white syndrome (AWS), a tissue loss disease that infected 25% of the A. cytherea population at Palmyra Atoll in 2009. OCN014 recreated signs of disease in experimentally infected corals in a temperature-dependent manner. Genes in OCN014 with expression levels positively correlated with temperature were identified using a transposon-mediated genetic screen. Mutant strains harbouring transposon insertions in two such genes, toxR (a toxin regulator) and mshA (the 11th gene of the 16-gene mannose-sensitive hemagglutinin (MSHA) type IV pilus operon), had reduced infectivity of A. cytherea. Deletion of toxR and the MSHA operon in a second strain of V. coralliilyticus, OCN008, that induces acute Montipora white syndrome in a temperature-independent manner had similarly reduced virulence. This work provides a link between temperature-dependent expression of virulence factors in a pathogen and infection of its coral host.

Diuretic Response: Clinical and Hemodynamic Predictors and Relation to Clinical Outcome.

OBJECTIVE: The aims of this work were to investigate the clinical and hemodynamic profile underlying the response to loop diuretics in acute decompensated heart failure (ADHF), and to compare the relative usefulness of measures of diuretic resistance for predicting mortality. METHODS AND RESULTS: We studied 475 patients with ADHF, of whom 241 underwent right heart catheterization. Linear regression models were used to identify factors that affected urine output. Loop diuretics response was estimated as (1) net fluid loss per 40 mg furosemide equivalents and (2) urine output produced per 40 mg furosemide equivalents. In a multivariable regression model, key independent predictors of urine output included diuretic dose (partial r = 0.44), baseline renal function (partial r = 0.38), systolic blood pressure (partial r = 0.26), and fluid intake (partial r = 0.31; all P < .0001). Among hemodynamic variables, elevated right atrial pressure was associated with greater urine output (partial r = 0.19; P = .002). The partial correlation attributable to diuretic dose (partial R2 = 0.19) accounted for approximately one-half of the variance in urine output explained by the model (model R2 = 0.40).Cox regression models demonstrated inverse relationships between quartiles of net fluid loss (P = .004) and quartiles of urine output (P = .04) per 40 mg furosemide and 6-month mortality. When comparing nested models, the model based on net fluid loss was better than the model based on urine output for the prediction of mortality (χ2 = 8.1; 3 df; P = .04). CONCLUSIONS: In patients with ADHF, beyond diuretic dose, other parameters including renal function, hemodynamic status, the degree of volume overload, and fluids intake also affect urine output. Measures of loop diuretic response are associated with short-term mortality.

Cumulative exposure to short sleep and body mass outcomes: a prospective study.

Short sleep duration is associated with excess body mass among adolescents and young adults. The mechanisms theorized to drive that association suggest that persistent exposure to short sleep should be associated with greater accumulations of body mass. We use prospective cohort data from four waves of the National Longitudinal Study of Adolescent to Adult Health (1994-2009; n = 14 800) to examine associations between cumulative exposure to short sleep throughout adolescence and early adulthood and obesity and elevated waist circumference outcomes. We compare several clinical and distribution-based standards of short sleep to assess which measures are associated most strongly with body mass. Cumulative exposure to short sleep exhibits dose-response associations with obesity and elevated waist circumference. Relative to respondents with no instances of short sleep, those who slept -0.50 standard deviations or less than the age and sex-specific average sleep hours in all four waves had 1.45 [95% confidence interval (CI): 1.03, 2.04] times the odds of being obese and 1.45 (95% CI: 1.02, 2.06) times the odds of having an elevated waist circumference. Our findings suggest that cumulative exposure to short sleep during adolescence and young adulthood may play an important role in the etiology of obesity and elevated waist circumference during this important developmental period.

The trpE gene negatively regulates differentiation of heterocysts at the level of induction in Anabaena sp. strain PCC 7120.

Levels of 2-oxoglutarate (2-OG) reflect nitrogen status in many bacteria. In heterocystous cyanobacteria, a spike in the 2-OG level occurs shortly after the removal of combined nitrogen from cultures and is an integral part of the induction of heterocyst differentiation. In this work, deletion of one of the two annotated trpE genes in Anabaena sp. strain PCC 7120 resulted in a spike in the 2-OG level and subsequent differentiation of a wild-type pattern of heterocysts when filaments of the mutant were transferred from growth on ammonia to growth on nitrate. In contrast, 2-OG levels were unaffected in the wild type, which did not differentiate under the same conditions. An inverted-repeat sequence located upstream of trpE bound a central regulator of differentiation, HetR, in vitro and was necessary for HetR-dependent transcription of a reporter fusion and complementation of the mutant phenotype in vivo. Functional complementation of the mutant phenotype with the addition of tryptophan suggested that levels of tryptophan, rather than the demonstrated anthranilate synthase activity of TrpE, mediated the developmental response of the wild type to nitrate. A model is presented for the observed increase in 2-OG in the trpE mutant.

Monitoring receipt of seasonal influenza vaccines with BRFSS and NHIS data: challenges and solutions.

Despite the availability of vaccines that mitigate the health risks associated with seasonal influenza, most individuals in the U.S. remain unvaccinated. Monitoring vaccination uptake for seasonal influenza, especially among disadvantaged or high-risk groups, is therefore an important public health activity. The Behavioral Risk Factor Surveillance System (BRFSS) - the largest telephone-based health surveillance system in the world - is an important resource in monitoring population health trends, including influenza vaccination. However, due to limitations in the question that measures influenza vaccination status, difficulties arise in estimating seasonal vaccination rates. Although researchers have proposed various methodologies to address this issue, no systematic review of these methodologies exists. By subjecting these methods to tests of sensitivity and specificity, we identify their strengths and weaknesses and advance a new method for estimating national and state-level vaccination rates with BRFSS data. To ensure that our findings are not anomalous to the BRFSS, we also analyze data from the National Health Interview Survey (NHIS). For both studies, we find that restricting the sample to interviews conducted between January and September offers the best balance of sensitivity (>90% on average), specificity (>90% on average), and statistical power (retention of 92.2% of vaccinations from the target flu season) over other proposed methods. We conclude that including survey participants from these months provides a simple and effective way to estimate seasonal influenza vaccination rates with BRFSS and NHIS data, and we discuss potential ways to better estimate vaccination rates in future epidemiologic surveys.

Vibrio coralliilyticus strain OCN008 is an etiological agent of acute Montipora white syndrome.

Identification of a pathogen is a critical first step in the epidemiology and subsequent management of a disease. A limited number of pathogens have been identified for diseases contributing to the global decline of coral populations. Here we describe Vibrio coralliilyticus strain OCN008, which induces acute Montipora white syndrome (aMWS), a tissue loss disease responsible for substantial mortality of the coral Montipora capitata in Kane'ohe Bay, Hawai'i. OCN008 was grown in pure culture, recreated signs of disease in experimentally infected corals, and could be recovered after infection. In addition, strains similar to OCN008 were isolated from diseased coral from the field but not from healthy M. capitata. OCN008 repeatedly induced the loss of healthy M. capitata tissue from fragments under laboratory conditions with a minimum infectious dose of between 10(7) and 10(8) CFU/ml of water. In contrast, Porites compressa was not infected by OCN008, indicating the host specificity of the pathogen. A decrease in water temperature from 27 to 23°C affected the time to disease onset, but the risk of infection was not significantly reduced. Temperature-dependent bleaching, which has been observed with the V. coralliilyticus type strain BAA-450, was not observed during infection with OCN008. A comparison of the OCN008 genome to the genomes of pathogenic V. coralliilyticus strains BAA-450 and P1 revealed similar virulence-associated genes and quorum-sensing systems. Despite this genetic similarity, infections of M. capitata by OCN008 do not follow the paradigm for V. coralliilyticus infections established by the type strain.

The impact of obesity on US mortality levels: the importance of age and cohort factors in population estimates.

OBJECTIVES: To estimate the percentage of excess death for US Black and White men and women associated with high body mass, we examined the combined effects of age variation in the obesity-mortality relationship and cohort variation in age-specific obesity prevalence. METHODS: We examined 19 National Health Interview Survey waves linked to individual National Death Index mortality records, 1986-2006, for age and cohort patterns in the population-level association between obesity and US adult mortality. RESULTS: The estimated percentage of adult deaths between 1986 and 2006 associated with overweight and obesity was 5.0% and 15.6% for Black and White men, and 26.8% and 21.7% for Black and White women, respectively. We found a substantially stronger association than previous research between obesity and mortality risk at older ages, and an increasing percentage of mortality attributable to obesity across birth cohorts. CONCLUSIONS: Previous research has likely underestimated obesity's impact on US mortality. Methods attentive to cohort variation in obesity prevalence and age variation in obesity's effect on mortality risk suggest that obesity significantly shapes US mortality levels, placing it at the forefront of concern for public health action.

Fluid loss, venous congestion, and worsening renal function in acute decompensated heart failure.

AIMS: To investigate the relationship between decongestion, central venous pressure, and risk of worsening renal function (WRF) in patients with acute decompensated heart failure (ADHF). METHODS AND RESULTS: We studied 475 patients with ADHF, of whom 238 underwent right heart catheterization. Right atrial pressure (RAP) was measured at baseline and at 24 h. Net fluid loss was recorded in the first 24 h. WRF was defined as a >0.3 mg/dL increase in serum creatinine above baseline. WRF occurred in 84 catheterized patients (35.3%). There was a weak correlation between baseline RAP and baseline estimated glomerular filtration rate (r = -0.17, P = 0.009). The amount of fluid removed during the first 24 h did not correlate with the magnitude of RAP reduction (r = 0.06, P = 0.35). No association was observed between WRF and baseline RAP [odds ratio (OR) 1.06, 95% confidence interval (CI) 0.80-1.41, P = 0.68 per 6.6 mmHg] or the decrease in RAP (adjusted OR 1.13, 95% CI 0.85-1.49, P = 0.40 per 5.3 mmHg reduction in RAP). In contrast, smaller net fluid loss was strongly associated with increased WRF risk. Compared with the first net fluid loss tertile, the adjusted OR was 1.85 (95% CI 0.90-3.80, P = 0.10) and 2.58 (95% CI 1.27-5.25; P = 0.009) for the second and third tertile, respectively (P for trend <0.0001). CONCLUSION: Smaller early net fluid loss is associated with increased risk for WRF. RAP is not a reliable surrogate of the magnitude of decongestion and risk of WRF. Future research is necessary to determine if targeting congestion may help prevent WRF.

Hemodynamic determinants of dyspnea improvement in acute decompensated heart failure.

BACKGROUND: Dyspnea relief constitutes a major treatment goal and a key measure of treatment efficacy in decompensated heart failure. However, there are no data with regard to the relationship between hemodynamic measurements during treatment and dyspnea improvement. METHODS AND RESULTS: We studied 233 patients assigned to right heart catheterization in the Vasodilation in the Management of Acute Congestive Heart Failure trial. Dyspnea (assessed using a 7-point Likert scale) and hemodynamic parameters were measured simultaneously at 15 and 30 minutes and 1, 2, 3, 6, and 24 hours. Dyspnea relief was defined as moderate or marked improvement. There was a time-dependent association between the reductions in pulmonary capillary wedge pressure (PCWP; 25.4, 24.6, 24.0, 23.5, 23.4, 21.5, and 19.9 mm Hg) and the percentage of patients achieving dyspnea relief (17.7%, 24.6%, 32.2%, 36.2%, 37.8%, 47.4%, and 66.1%, in the respective time points). Multivariable logistic generalized estimating equations modeling demonstrated that reductions of both PCWP and mean pulmonary artery pressure were independently associated with dyspnea relief. Compared with the highest PCWP quartile, the adjusted odds ratios for dyspnea relief were 0.92 (95% confidence interval [CI], 0.67-1.29), 1.07 (95% CI, 0.75-1.55), and 1.80 (95% CI, 1.22-2.65) in the third, second, and first PCWP quartiles, respectively (P(trend)=0.003). Compared with the highest mean pulmonary artery pressure quartile, the adjusted odds ratios for dyspnea relief were 2.0 (95% CI, 1.41-2.82), 2.23 (95% CI, 1.52-3.27), and 2.98 (95% CI, 1.91-4.66) in the third, second, and first mean pulmonary artery pressure quartiles, respectively (P(trend)<0.0001). CONCLUSIONS: A clinically significant improvement in dyspnea is associated with a reduction in both PCWP and mean pulmonary artery pressure.

Herpes simplex virus-1 encephalitis: a review of current disease management with three case reports.

Herpes simplex virus-1 (HSV-1) is the most common cause of lethal sporadic encephalitis. Despite improved therapy with intraveneous acyclovir, HSV-1 encephalitis is associated with persistent severe neurological deficits. We report three cases of adult patients with HSV-1 encephalitis (HSE), discuss the current accepted guidelines for treatment as published by the Infectious Disease Society of America (IDSA) and review the literature pertaining to HSE. Our case presentations are consistent with the literature review noting a broad spectrum of clinical outcomes with HSE. We include the first published case of successful early transition to oral antiviral therapy. In the other two cases, repeat cerebrospinal fluid (CSF) analysis showed persistent lymphocytic pleocytosis necessitating prolonged viral suppression. Long-term neurological sequelae were noted in these two patients. The IDSA recommendation of 2-3 weeks of intraveneous acyclovir at 10 mg/kg every 8 h, depending on the clinical course, is sufficient for most cases of HSE. We recommend individualization of duration of treatment based on follow-up CSF analysis with quantification of HSV-1.