We aimed to assess the profile of respiratory viruses in young children hospitalized for acute lower respiratory tract infection (ALRI) and its association with disease severity, defined as need for ...pediatric intensive care unit (PICU) admission.
Prospective observational cohort study.
A tertiary-care university hospital in Brazil.
Children younger than three years attending the pediatric emergency room with ALRI who were admitted to the hospital.
None.
Nasopharyngeal aspirates were collected from patients from June 1st, 2008 to May 31st, 2009within the first 48 hours of hospitalization. Nasopharyngeal aspirates were tested for 17humanrespiratory viruses by molecular and immunofluorescence based assays. Simple and multiple log-binomial regression models were constructed to assess associations of virus type with a need for PICU admission. Age, prematurity, the presence of an underlying disease and congenital heart disease were covariates. Nasopharyngeal aspirates were positive for at least one virus in 236 patients. Rhinoviruses were detected in 85.6% of samples, with a preponderance of rhinovirus C (RV-C) (61.9%). Respiratory syncytial virus was detected in 59.8% and human coronavirus (HCoV) in 11% of the samples. Co-detections of two to five viruses were found in 78% of the patients. The detection of HCoV alone (adjusted relative risk (RR) 2.18; 95% CI 1.15-4.15) or in co-infection with RV-C (adjusted RR 2.37; 95% CI 1.23-4.58) was independently associated with PICU admission.
The detection of HCoV alone or in co-infection with RV-C was independently associated with PICU admission in young children hospitalized for ALRI.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Transcription and pre-mRNA splicing are key steps in the control of gene expression and mutations in genes regulating each of these processes are common in leukaemia
. Despite the frequent overlap of ...mutations affecting epigenetic regulation and splicing in leukaemia, how these processes influence one another to promote leukaemogenesis is not understood and, to our knowledge, there is no functional evidence that mutations in RNA splicing factors initiate leukaemia. Here, through analyses of transcriptomes from 982 patients with acute myeloid leukaemia, we identified frequent overlap of mutations in IDH2 and SRSF2 that together promote leukaemogenesis through coordinated effects on the epigenome and RNA splicing. Whereas mutations in either IDH2 or SRSF2 imparted distinct splicing changes, co-expression of mutant IDH2 altered the splicing effects of mutant SRSF2 and resulted in more profound splicing changes than either mutation alone. Consistent with this, co-expression of mutant IDH2 and SRSF2 resulted in lethal myelodysplasia with proliferative features in vivo and enhanced self-renewal in a manner not observed with either mutation alone. IDH2 and SRSF2 double-mutant cells exhibited aberrant splicing and reduced expression of INTS3, a member of the integrator complex
, concordant with increased stalling of RNA polymerase II (RNAPII). Aberrant INTS3 splicing contributed to leukaemogenesis in concert with mutant IDH2 and was dependent on mutant SRSF2 binding to cis elements in INTS3 mRNA and increased DNA methylation of INTS3. These data identify a pathogenic crosstalk between altered epigenetic state and splicing in a subset of leukaemias, provide functional evidence that mutations in splicing factors drive myeloid malignancy development, and identify spliceosomal changes as a mediator of IDH2-mutant leukaemogenesis.
In this document, the Inter-American Committee of Cardiovascular Prevention and Rehabilitation, together with the South American Society of Cardiology, aimed to formulate strategies, measures, and ...actions for cardiovascular disease prevention and rehabilitation (CVDPR). In the context of the implementation of a regional and national health policy in Latin American countries, the goal is to promote cardiovascular health and thereby decrease morbidity and mortality. The study group on Cardiopulmonary and Metabolic Rehabilitation from the Department of Exercise, Ergometry, and Cardiovascular Rehabilitation of the Brazilian Society of Cardiology has created a committee of experts to review the Portuguese version of the guideline and adapt it to the national reality. The mission of this document is to help health professionals to adopt effective measures of CVDPR in the routine clinical practice. The publication of this document and its broad implementation will contribute to the goal of the World Health Organization (WHO), which is the reduction of worldwide cardiovascular mortality by 25% until 2025. The study group's priorities are the following: • Emphasize the important role of CVDPR as an instrument of secondary prevention with significant impact on cardiovascular morbidity and mortality; • Join efforts for the knowledge on CVDPR, its dissemination, and adoption in most cardiovascular centers and institutes in South America, prioritizing the adoption of cardiovascular prevention methods that are comprehensive, practical, simple and which have a good cost/benefit ratio; • Improve the education of health professionals and patients with education programs on the importance of CVDPR services, which are directly targeted at the health system, clinical staff, patients, and community leaders, with the aim of decreasing the barriers to CVDPR implementation.
We tested the hypothesis that concentrations of adipocytokines are altered in SLE and associated with coronary atherosclerosis, insulin resistance and inflammation. Concentrations of resistin, ...leptin, adiponectin and visfatin were measured in 109 patients with SLE and 78 control subjects. Coronary calcification was measured using electron beam-computed tomography, and insulin resistance was defined by the homeostasis model assessment index. Concentrations of adiponectin (28.7 ± 17.9 vs 22.0 ± 15.3 μg/mL, P = 0.003), leptin (41.1 ± 49.9 vs 19.8 ± 24.6 ng/mL, P < 0.001) and visfatin (7.5 ± 10.5 vs 4.5 ± 2.8 ng/mL, P < 0.001) were higher in patients with SLE than in controls. These differences remained significant after adjustment for age, race, sex and body mass index (BMI; all P values < 0.02). Concentrations of resistin (10.7 ± 7.6 vs 9.1 ± 5.1 ng/mL, P = 0.41) did not differ in patients and controls. In patients with SLE, leptin was positively associated with BMI (ρ = 0.80, P < 0.001), insulin resistance (ρ = 0.46, P < 0.001) and C-reactive protein (CRP) (ρ = 0.30, P = 0.002), whereas adiponectin was negatively associated with the same factors (ρ = –0.40, P < 0.001; ρ = −0.38, P < 0.001; ρ = –0.22, P = 0.02, respectively). None of the adipocytokines were associated with coronary atherosclerosis in SLE. In conclusion, patients with SLE have increased concentrations of adiponectin, leptin and visfatin. Lower concentrations of adiponectin and higher concentrations of leptin are associated with insulin resistance, BMI and CRP in patients with SLE.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
PURPOSE:Single-incision laparoscopic surgery is gaining momentum in general surgery but it is essentially unstudied for laparoscopic colectomy. The aim of our study was to compare outcomes for ...single-incision laparoscopic colectomy with laparoscopic-assisted colectomy.
METHODS:Patients undergoing laparoscopic colectomy were prospectively entered into an institutional review board-approved database. Those that underwent single-incision laparoscopic colectomy were case matched for sex, age, disease, surgery, body mass index, previous surgeries, and surgeon with patients undergoing LAC.
RESULTS:Twenty-nine single-incision laparoscopic segmental colectomies were performed for polyps (4), adenocarcinoma (12), diverticulitis (6), and Crohnʼs disease (7) and were case matched to laparoscopic-assisted colectomy for the same indications. Mean body mass index was 28.8 ± 3 kg/m. Operative time was longer for single-incision laparoscopic colectomy (134.4 ± 40 vs 103.8 ± 54 min; P = .0002). Four single-incision laparoscopic colectomies were converted to LAC requiring either one extra port (2) or 2 extra ports (2), and there was one conversion to laparotomy. Extraction scar length (millimeters) was similar (38 ± 6.0 vs 45 ± 6.2; P = .746). Postoperative morbidity (5/29 vs 7/29; P = .284) and length of stay (day) (3.7 ± 1.1 vs 3.9 ± 1.1; P = .445) were similar between groups.
CONCLUSIONS:Single-incision laparoscopic colectomy is feasible and safe but takes more time than laparoscopic-assisted colectomy. Although results approximate those for laparoscopic-assisted colectomy, an additional learning curve is involved, and extra incisions are sometimes required. Single-incision laparoscopic colectomy requires further prospective validation so that the cost of the device can be justified by an improved clinical outcome.
One century after its formulation, Einstein's general relativity (GR) has made remarkable predictions and turned out to be compatible with all experimental tests. Most of these tests probe the theory ...in the weak-field regime, and there are theoretical and experimental reasons to believe that GR should be modified when gravitational fields are strong and spacetime curvature is large. The best astrophysical laboratories to probe strong-field gravity are black holes and neutron stars, whether isolated or in binary systems. We review the motivations to consider extensions of GR. We present a (necessarily incomplete) catalog of modified theories of gravity for which strong-field predictions have been computed and contrasted to Einstein's theory, and we summarize our current understanding of the structure and dynamics of compact objects in these theories. We discuss current bounds on modified gravity from binary pulsar and cosmological observations, and we highlight the potential of future gravitational wave measurements to inform us on the behavior of gravity in the strong-field regime.
We develop a framework for joint constraints on the CO luminosity function based on power spectra (PS) and voxel intensity distributions (VID) and apply this to simulations of CO Mapping Array ...Pathfinder (COMAP), a CO intensity mapping experiment. This Bayesian framework is based on a Markov chain Monte Carlo (MCMC) sampler coupled to a Gaussian likelihood with a joint PS + VID covariance matrix computed from a large number of fiducial simulations and re-calibrated with a small number of simulations per MCMC step. The simulations are based on dark matter halos from fast peak patch simulations combined with the LCO(Mhalo) model of Li et al. We find that the relative power to constrain the CO luminosity function depends on the luminosity range of interest. In particular, the VID is more sensitive at large luminosities, while the PS and the VID are both competitive at small and intermediate luminosities. The joint analysis is superior to using either observable separately. When averaging over CO luminosities ranging between , and over 10 cosmological realizations of COMAP Phase 2, the uncertainties (in dex) are larger by 58% and 30% for the PS and VID, respectively, when compared to the joint analysis (PS + VID). This method is generally applicable to any other random field, with a complicated likelihood, as long a fast simulation procedure is available.
•Pedestrian crash decrease within two years after implementing VZ corridor upgrades.•The impact of gradual implementation is estimated using project completion dates.•A before-and-after treatment and ...control spatial point process analysis is conducted.•VZ corridor upgrades contribute to significant crash reductions on treated sites.•Greater crash dispersion is observed at the local level along treated corridors.
The long-term effects of the Vision-Zero (VZ) approach in Scandinavia are well documented. In contrast, information regarding the immediate effects of VZ at the starting phase upon gradual implementation is scarce. Taking New York City as the case study, we analyzed both the local and global effects of the Vision-Zero gradual implementation on pedestrian crashes in the early stage of implementation starting from 2014. The data analysis comprised 8,165 pedestrian injury crashes. Using location data, the crashes were matched to VZ infrastructure improvement location, start and completion dates. The experimental design included a treatment and two types of control conditions, and we controlled for well-known covariates including traffic exposure, land use, and risk-prone areas. We estimated a Geyer Saturation model and kernel density function for modeling the effect of Vision-Zero on crash intensity and dispersion two years before and after the implementation of Vision-Zero. The results reveal a significant global decrease of 6.1 % (p = 0.004) in pedestrian crash incidence in the treated sections compared with the control group two years after the treatment, and a greater dispersion of pedestrian injuries following the policy implementation.
Objectives
Sodium (Na+) is stored in the skin and muscle and plays an important role in immune regulation. In animal models, increased tissue Na+ is associated with activation of the immune system, ...and high salt intake exacerbates autoimmune disease and worsens hypertension. However, there is no information about tissue Na+ and human autoimmune disease. We hypothesized that muscle and skin Na+ content is (a) higher in patients with systemic lupus erythematosus (SLE) than in control subjects, and (b) associated with blood pressure, disease activity, and inflammation markers (interleukin (IL)-6, IL-10 and IL-17 A) in SLE.
Methods
Lower-leg skin and muscle Na+ content was measured in 23 patients with SLE and in 28 control subjects using 23Na+ magnetic resonance imaging. Demographic and clinical information was collected from interviews and chart review, and blood pressure was measured. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI). Plasma inflammation markers were measured by multiplex immunoassay.
Results
Muscle Na+ content was higher in patients with SLE (18.8 (16.7–18.3) mmol/L) than in control subjects (15.8 (14.7–18.3) mmol/L; p < 0.001). Skin Na+ content was also higher in SLE patients than in controls, but this difference was not statistically significant. Among patients with SLE, muscle Na+ was associated with SLEDAI and higher concentrations of IL-10 after adjusting for age, race, and sex. Skin Na+ was significantly associated with systolic blood pressure, but this was attenuated after covariate adjustment.
Conclusion
Patients with SLE had higher muscle Na+ content than control subjects. In patients with SLE, higher muscle Na+ content was associated with higher disease activity and IL-10 concentrations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE: Long-acting opioids increase the risk of unintentional overdose deaths but also may increase mortality from cardiorespiratory and other causes. OBJECTIVE: To compare all-cause mortality ...for patients with chronic noncancer pain who were prescribed either long-acting opioids or alternative medications for moderate to severe chronic pain. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study between 1999 and 2012 of Tennessee Medicaid patients with chronic noncancer pain and no evidence of palliative or end-of-life care. EXPOSURES: Propensity score–matched new episodes of prescribed therapy for long-acting opioids or either analgesic anticonvulsants or low-dose cyclic antidepressants (control medications). MAIN OUTCOMES AND MEASURES: Total and cause-specific mortality as determined from death certificates. Adjusted hazard ratios (HRs) and risk differences (difference in incidence of death) were calculated for long-acting opioid therapy vs control medication. RESULTS: There were 22 912 new episodes of prescribed therapy for both long-acting opioids and control medications (mean SD age, 48 11 years; 60% women). The long-acting opioid group was followed up for a mean 176 days and had 185 deaths and the control treatment group was followed up for a mean 128 days and had 87 deaths. The HR for total mortality was 1.64 (95% CI, 1.26-2.12) with a risk difference of 68.5 excess deaths (95% CI, 28.2-120.7) per 10 000 person-years. Increased risk was due to out-of-hospital deaths (154 long-acting opioid, 60 control deaths; HR, 1.90; 95% CI, 1.40-2.58; risk difference, 67.1; 95% CI, 30.1-117.3) excess deaths per 10 000 person-years. For out-of-hospital deaths other than unintentional overdose (120 long-acting opioid, 53 control deaths), the HR was 1.72 (95% CI, 1.24-2.39) with a risk difference of 47.4 excess deaths (95% CI, 15.7-91.4) per 10 000 person-years. The HR for cardiovascular deaths (79 long-acting opioid, 36 control deaths) was 1.65 (95% CI, 1.10-2.46) with a risk difference of 28.9 excess deaths (95% CI, 4.6-65.3) per 10 000 person-years. The HR during the first 30 days of therapy (53 long-acting opioid, 13 control deaths) was 4.16 (95% CI, 2.27-7.63) with a risk difference of 200 excess deaths (95% CI, 80-420) per 10 000 person-years. CONCLUSIONS AND RELEVANCE: Prescription of long-acting opioids for chronic noncancer pain, compared with anticonvulsants or cyclic antidepressants, was associated with a significantly increased risk of all-cause mortality, including deaths from causes other than overdose, with a modest absolute risk difference. These findings should be considered when evaluating harms and benefits of treatment.
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