Background
Studies of autopsies of military members dying in three US wars indicate that the prevalence of atherosclerosis in successive cohorts of healthy young men and women has dramatically ...decreased over the past half century.
Objective
The objective of this study was to compare the decline in the prevalence of atherosclerosis and myocardial infarction with previously published studies on the decline in the prevalence of duodenal ulcer.
Methods
A plot of the prevalence of coronary atherosclerosis and the prevalence of myocardial infarction in three cohorts of young men and women born from 1930 to 1980 was constructed.
Results
The figure shows a marked decline in prevalence in atherosclerosis beginning in a military cohort born around 1930 and a similar marked decline in prevalence of myocardial infarction in the US population beginning in 1970. In published studies duodenal ulcer began to decline in prevalence in 1960. As duodenal ulcers began to occur at age 30 and myocardial infarctions began to occur at age 40 at the time of peak prevalence, the cohort born in 1930 was the first to experience a decline in prevalence of both duodenal ulcer and heart attacks.
Conclusion
The study shows that the decline in heart attacks is temporally related to the decline in duodenal ulcer and by inference, Helicobacter pylori infection.
Intraspecific variation in host susceptibility to individual parasite species is common, yet how these effects scale to mediate the structure of diverse parasite communities in nature is less well ...understood. To address this knowledge gap, we tested how host genetic identity affects parasite communities on restored reefs seeded with juvenile oysters from different sources-a regional commercial hatchery or one of two wild progenitor lines. We assessed prevalence and intensity of three micro- and two macroparasite species for 4 years following restoration. Despite the spatial proximity of restored reefs, oyster source identity strongly predicted parasite community prevalence across all years, with sources varying in their relative susceptibility to different parasites. Oyster seed source also predicted reef-level parasite intensities across space and through time. Our results highlight that host intraspecific variation can shape parasite community structure in natural systems, and reinforce the importance of considering source identity and diversity in restoration design.
The rat has been used extensively as a model for evaluating chemical toxicities and for understanding drug mechanisms. However, its transcriptome across multiple organs, or developmental stages, has ...not yet been reported. Here we show, as part of the SEQC consortium efforts, a comprehensive rat transcriptomic BodyMap created by performing RNA-Seq on 320 samples from 11 organs of both sexes of juvenile, adolescent, adult and aged Fischer 344 rats. We catalogue the expression profiles of 40,064 genes, 65,167 transcripts, 31,909 alternatively spliced transcript variants and 2,367 non-coding genes/non-coding RNAs (ncRNAs) annotated in AceView. We find that organ-enriched, differentially expressed genes reflect the known organ-specific biological activities. A large number of transcripts show organ-specific, age-dependent or sex-specific differential expression patterns. We create a web-based, open-access rat BodyMap database of expression profiles with crosslinks to other widely used databases, anticipating that it will serve as a primary resource for biomedical research using the rat model.
Few studies have examined patterns of specific sleep problems among individuals with osteoarthritis (OA). The primary objective of this study was to examine prevalence of symptoms of insomnia and ...obstructive sleep apnea (OSA) among Veterans with OA. Secondary objectives were to assess proportions of individuals with insomnia and OSA symptoms who may have been undiagnosed and to examine Veterans' characteristics associated with insomnia and OSA symptoms.
Veterans (n = 300) enrolled in a clinical trial completed the Insomnia Severity Index (ISI) and the Berlin Questionnaire (BQ) at baseline; proportions of participants with symptoms consistent with insomnia and OSA were calculated, using standard cut-offs for ISI and BQ. For Veterans with insomnia and OSA symptoms, electronic medical records were searched to identify whether there was a diagnosis code for these conditions. Multivariable linear (ISI) and logistic (BQ) regression models examined associations of the following characteristics with symptoms of insomnia and OSA: age, gender, race, self-reported general health, body mass index (BMI), diagnosis of post-traumatic stress disorder (PTSD), pain severity, depressive symptoms, number of joints with arthritis symptoms and opioid use.
Symptoms consistent with insomnia and OSA were found in 53 and 66% of this sample, respectively. Among participants screening positive for insomnia and OSA, diagnosis codes for these disorders were present in the electronic medical record for 22 and 51%, respectively. Characteristics associated with insomnia were lower age (β (SE) = - 0.09 (0.04), 95% confidence interval CI = - 0.16, - 0.02), having a PTSD diagnosis (β (SE) = 1.68 (0.73), CI = 0.25, 3.11), greater pain severity (β (SE) = 0.36 (0.09), CI = 0.17, 0.55), and greater depressive symptoms (β (SE) = 0.84 (0.07), CI = 0.70, 0.98). Characteristics associated with OSA were higher BMI (odds ratio OR = 1.13, CI = 1.06, 1.21), greater depressive symptoms (OR = 1.12, CI = 1.05, 1.20), and opioid use (OR = 0.51, CI = 0.26, 0.99).
Insomnia and OSA symptoms were very common in Veterans with OA, and a substantial proportion of individuals with symptoms may have been undiagnosed. Characteristics associated with insomnia and OSA symptoms were consistent with prior studies.
NCT01130740 .
To develop a clinical practice guideline for red blood cell transfusion in adult trauma and critical care.
Meetings, teleconferences and electronic-based communication to achieve grading of the ...published evidence, discussion and consensus among the entire committee members.
This practice management guideline was developed by a joint taskforce of EAST (Eastern Association for Surgery of Trauma) and the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM). We performed a comprehensive literature review of the topic and graded the evidence using scientific assessment methods employed by the Canadian and U.S. Preventive Task Force (Grading of Evidence, Class I, II, III; Grading of Recommendations, Level I, II, III). A list of guideline recommendations was compiled by the members of the guidelines committees for the two societies. Following an extensive review process by external reviewers, the final guideline manuscript was reviewed and approved by the EAST Board of Directors, the Board of Regents of the ACCM and the Council of SCCM.
Key recommendations are listed by category, including (A) Indications for RBC transfusion in the general critically ill patient; (B) RBC transfusion in sepsis; (C) RBC transfusion in patients at risk for or with acute lung injury and acute respiratory distress syndrome; (D) RBC transfusion in patients with neurologic injury and diseases; (E) RBC transfusion risks; (F) Alternatives to RBC transfusion; and (G) Strategies to reduce RBC transfusion.
Evidence-based recommendations regarding the use of RBC transfusion in adult trauma and critical care will provide important information to critical care practitioners.
Cryptococcus neoformans is an opportunistic fungal pathogen and a leading cause of fungal-infection-related fatalities, especially in immunocompromised hosts. Several virulence factors are known to ...play a major role in the pathogenesis of cryptococcal infections, including the enzyme phospholipase B1 (Plb1). Compared to other well-studied Cryptococcus neoformans virulence factors such as the polysaccharide capsule and melanin production, very little is known about the contribution of Plb1 to cryptococcal virulence. Phospholipase B1 is a phospholipid-modifying enzyme that has been implicated in multiple stages of cryptococcal pathogenesis, including initiation and persistence of pulmonary infection and dissemination to the central nervous system, but the underlying reason for these phenotypes remains unknown. Here we demonstrate that a Δplb1 knockout strain of C. neoformans has a profound defect in intracellular growth within host macrophages. This defect is due to a combination of a 50% decrease in proliferation and a 2-fold increase in cryptococcal killing within the phagosome. In addition, we show for the first time that the Δplb1 strain undergoes a morphological change during in vitro and in vivo intracellular infection, resulting in a subpopulation of very large titan cells, which may arise as a result of the attenuated mutant's inability to cope within the macrophage.
Bacterial usage of the cyclic dinucleotide c‐di‐GMP is widespread, governing the transition between motile/sessile and unicellular/multicellular behaviors. There is limited information on c‐di‐GMP ...metabolism, particularly on regulatory mechanisms governing control of EAL c‐di‐GMP phosphodiesterases. Herein, we provide high‐resolution structures for an EAL enzyme Bd1971, from the predatory bacterium Bdellovibrio bacteriovorus, which is controlled by a second signaling nucleotide, cAMP. The full‐length cAMP‐bound form reveals the sensory N‐terminus to be a domain‐swapped variant of the cNMP/CRP family, which in the cAMP‐activated state holds the C‐terminal EAL enzyme in a phosphodiesterase‐active conformation. Using a truncation mutant, we trap both a half‐occupied and inactive apo‐form of the protein, demonstrating a series of conformational changes that alter juxtaposition of the sensory domains. We show that Bd1971 interacts with several GGDEF proteins (c‐di‐GMP producers), but mutants of Bd1971 do not share the discrete phenotypes of GGDEF mutants, instead having an elevated level of c‐di‐GMP, suggesting that the role of Bd1971 is to moderate these levels, allowing “action potentials” to be generated by each GGDEF protein to effect their specific functions.
Synopsis
The cyclic‐di‐GMP hydrolase Bd1971 is a sensor‐enzyme fusion protein controlling turnover and predatory behavior of the bacterium Bdellovibrio bacteriovorus. Here, structural work combined with enzyme assays and genetics reveal regulation of Bd1971 by cAMP, with important consequences for signalling during the Bdellovibrio lifecycle.
The Bd1971 structure identifies a sensor adapted from the dimeric CRP superfamily.
Bd1971 bound to stimulus cAMP renders the protein active to hydrolyse cyclic‐di‐GMP.
Empty and part‐occupied sensor structures reveal a “swing‐out” mechanism of regulation.
Bd1971 can bind GGDEF synthases and putatively allow “action potential” spikes of cyclic‐di‐GMP to be generated.
Structural and biochemical work shows how usage of the second messenger cyclic dinucleotide c‐di‐GMP is controlled by upstream cAMP.
Several years after sequencing the human genome and the mouse genome, much remains to be discovered about the functions of most human and mouse genes. Computational prediction of gene function ...promises to help focus limited experimental resources on the most likely hypotheses. Several algorithms using diverse genomic data have been applied to this task in model organisms; however, the performance of such approaches in mammals has not yet been evaluated.
In this study, a standardized collection of mouse functional genomic data was assembled; nine bioinformatics teams used this data set to independently train classifiers and generate predictions of function, as defined by Gene Ontology (GO) terms, for 21,603 mouse genes; and the best performing submissions were combined in a single set of predictions. We identified strengths and weaknesses of current functional genomic data sets and compared the performance of function prediction algorithms. This analysis inferred functions for 76% of mouse genes, including 5,000 currently uncharacterized genes. At a recall rate of 20%, a unified set of predictions averaged 41% precision, with 26% of GO terms achieving a precision better than 90%.
We performed a systematic evaluation of diverse, independently developed computational approaches for predicting gene function from heterogeneous data sources in mammals. The results show that currently available data for mammals allows predictions with both breadth and accuracy. Importantly, many highly novel predictions emerge for the 38% of mouse genes that remain uncharacterized.
A new data mode and new analysis methods are used to detect Terrestrial Gamma‐ray Flashes (TGFs) with the Fermi Gamma‐ray Burst Monitor (GBM) 10 times more frequently than previously. In 1037 h of ...observations at times and over regions for which TGFs are expected, 384 new TGFs were found in addition to the 39 TGFs and two Terrestrial Electron Beam events already detected without the new data mode and methodology. Cosmic ray showers were found to be an important background; they show characteristic signatures in the data of both GBM and the Fermi Large Area Telescope Calorimeter that enable their removal, leaving a sample estimated to consist of ≈98% TGFs. The sample includes shorter TGFs than previously found with GBM. The true duration distribution likely contains additional short TGFs because their detection by GBM is limited by detector dead time. One‐third of this sample has matches with locations from the World Wide Lightning Location Network (WWLLN)—maps of these locations show the geographic and meteorological features more clearly than maps of spacecraft locations. The intrinsic TGF rate is evaluated using the lightning rate maps of the Lightning Imaging Sensor, accounting for the detection efficiency of GBM as a function of spacecraft‐source offset, from which we estimate a global TGF rate of ≈400,000 per year. With continuous production of data in the new mode we estimate that GBM will detect ≈850 TGFs per year.
Key Points
A new data mode and analysis techniques increase the TGF rate of GBM x10.
Shorter TGFs are detected.
The global TGF rate is estimated as about 400,000 per year.
It is well established that individuals differ in their response to sleep loss. However, existing methods to predict an individual's sleep-loss phenotype are not scalable or involve effort-dependent ...neurobehavioural tests. To overcome these limitations, we sought to predict an individual's level of resilience or vulnerability to sleep loss using electroencephalographic (EEG) features obtained from routine night sleep. To this end, we retrospectively analysed five studies in which 96 healthy young adults (41 women) completed a laboratory baseline-sleep phase followed by a sleep-loss challenge. After classifying subjects into sleep-loss phenotypic groups, we extracted two EEG features from the first sleep cycle (median duration: 1.6 h), slow-wave activity (SWA) power and SWA rise rate, from four channels during the baseline nights. Using these data, we developed two sets of logistic regression classifiers (resilient versus not-resilient and vulnerable versus not-vulnerable) to predict the probability of sleep-loss resilience or vulnerability, respectively, and evaluated model performance using test datasets not used in model development. Consistently, the most predictive features came from the left cerebral hemisphere. For the resilient versus not-resilient classifiers, we obtained an average testing performance of 0.68 for the area under the receiver operating characteristic curve, 0.72 for accuracy, 0.50 for sensitivity, 0.84 for specificity, 0.61 for positive predictive value, and 3.59 for likelihood ratio. We obtained similar performance for the vulnerable versus not-vulnerable classifiers. These results indicate that logistic regression classifiers based on SWA power and SWA rise rate from routine night sleep can largely predict an individual's sleep-loss phenotype.
PDF
