Acquisition of direct antiviral effector functions by CMV-specific CD4+ T lymphocytes with cellular maturation

The role of CD4+ T cells in the control of persistent viral infections beyond the provision of cognate help remains unclear. We used polychromatic flow cytometry to evaluate the production of the cytokines interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-2, the chemokine macrophage inflammatory protein (MIP)-1beta, and surface mobilization of the degranulation marker CD107a by CD4+ T cells in response to stimulation with cytomegalovirus (CMV)-specific major histocompatibility complex class II peptide epitopes. Surface expression of CD45RO, CD27, and CD57 on responding cells was used to classify CD4+ T cell maturation. The functional profile of virus-specific CD4+ T cells in chronic CMV infection was unique compared with that observed in other viral infections. Salient features of this profile were: (a) the simultaneous production of MIP-1beta, TNF-alpha, and IFN-gamma in the absence of IL-2; and (b) direct cytolytic activity associated with surface mobilization of CD107a and intracellular expression of perforin and granzymes. This polyfunctional profile was associated with a terminally differentiated phenotype that was not characterized by a distinct clonotypic composition. Thus, mature CMV-specific CD4+ T cells exhibit distinct functional properties reminiscent of antiviral CD8+ T lymphocytes.     

Practice patterns of VTE chemoprophylaxis after discharge following hepatic and pancreatic resections for cancer: A survey of hepatopancreatobiliary surgeons

Journal of Thrombosis and Thrombolysis - Patients with hepatopancreatobiliary (HPB) malignancies undergoing resection are prone to venous thromboembolism (VTE), and current guidelines recommend up...     

Diagnostic evaluation of the MRP-8/14 for the emergency assessment of chest pain

Elevated levels of myeloid-related protein (MRP)-8/14 (S100A8/A9) are associated with first cardiovascular events in healthy individuals and worse prognosis in patients with acute coronary syndrome (ACS). The diagnostic utility of MRP-8/14 in patients presenting to the emergency room with symptoms concerning for ACS is uncertain. MRP-8/14 was measured in serial serum and plasma samples in a single center prospective cohort-study of patients presenting to the emergency room with non-traumatic chest pain concerning for ACS. Final diagnosis was adjudicated by an endpoint committee. Of patients with baseline MRP-8/14 results (n = 411), the median concentration in serum was 1.57 μg/ml (25th, 75th: 0.87, 2.68) and in plasma was 0.41 μg/ml (<0.4, 1.15) with only moderate correlation between serum and plasma (ρ = 0.40). A final diagnosis of MI was made in 106 (26%). Peak serum MRP-8/14 was higher in patients presenting with MI (p < 0.001). However, the overall diagnostic performance of MRP-8/14 was poor: sensitivity 28% (95% CI 20-38), specificity 82% (78-86), positive predictive value 36% (26-47), and negative predictive value 77% (72-81). The area under the ROC curve for diagnosis of MI with MRP-8/14 was 0.55 (95% CI 0.51-0.60) compared with 0.95 for cTnI. The diagnostic performance was not improved in early-presenters, patients with negative initial cTnI, or using later MRP-8/14 samples. Patients presenting with MI had elevated levels of serum MRP-8/14 compared to patients with non-cardiac chest pain. However, overall diagnostic performance of MRP-8/14 was poor and neither plasma nor serum MRP-8/14 offered diagnostic utility comparable to cardiac troponin.     

Three small nucleolar RNAs of unique nucleotide sequences.

Three small RNA species were detected in human cells, and their cDNAs were synthesized and cloned. These RNAs are nucleolar, are 207, 154, and 135 nucleotides long, and are named E1, E2, and E3, respectively, and their unique nucleotide sequences suggest that they may belong to an additional family of small nucleolar RNAs. The 5' ends of these three RNAs do not appear to have a trimethylguanosine cap or another type of cap. Apparent homologs of these three RNAs were detected in mouse, rabbit, and frog cells, suggesting their universal importance. They are housekeeping RNA species, since they are present in all rabbit tissues analyzed.     

Longitudinal caries prevalence in a comprehensive,multicomponent, school-based prevention program

BackgroundGlobally, children’s caries prevalence exceeds 30% and has not markedly changed in 30 years. School-based caries prevention programs can be an effective method to reduce caries prevalence, obviate traditional barriers to care, and use aerosol-free interventions. The objective of this study was to explore the clinical effectiveness of a comprehensive school-based, aerosol-free, caries prevention program.MethodsThe authors conducted a 6-year prospective open cohort study in 33 US public elementary schools, providing care to 6,927 children in communities with and without water fluoridation. After dental examinations, dental hygienists provided twice-yearly prophylaxis, glass ionomer sealants, glass ionomer interim therapeutic restorations, fluoride varnish, toothbrushes, fluoride toothpaste, oral hygiene instruction, and referral to community dentists as needed. The authors used generalized estimating equations to estimate the change in the prevalence of untreated caries over time.ResultsThe prevalence of untreated caries decreased by more than 50%: from 39% through 18% in phase 1, and from 28% through 10% in phase 2. The per-visit adjusted odds ratio of untreated caries was 0.79 (95% confidence interval, 0.73 to 0.85).Conclusions and Practical ImplicationsThis school-based comprehensive caries prevention program was associated with substantial reductions in children’s untreated caries, supporting the concept of expanding traditional practices to include office- and community-based aerosol-free care.     

Attention and organization of behavior in high-risk infants

Preterm infants at 7 months, corrected age, and 7-month-old full-term infants were videotaped while they played with a series of novel objects for a minute apiece. Each infant's videotape was scored for duration of examining (focused visual inspection), duration of mouthing, and duration of slapping or banging the objects. Full-term infants examined the objects significantly more than the preterms; the two groups showed equivalent levels of mouthing and banging. Each minute was then divided into 15-second segments. Only examining showed a decline over time, and then only for the full-terms. When the three behaviors were compared on the latency to the first episode of the behavior in each trial, it was found that the behavior of the full-terms was clearly differentiated in terms of sequence with examining having the shortest latency, mouthing the next shortest, and banging the longest. For the preterms, however, there were no differences among the mean latencies. The major difference between the two groups was in the latency to examine, which was significantly longer in the preterms. In general, the results for the preterms were not related to developmental level, but appeared to be due to deficits in both reactivity to stimulation and ability to sustain attention.     

Early intervention in the context of foster care

There may be a number of specific foster care models that would facilitate infant development. The important point is that the emphasis should shift from foster care as maintenance to foster care as active intervention. Several other recent developments in public policy and public opinion suggest that the time is ripe for such a change; the federal government has mandated provision of early intervention services for young children at risk, and there is renewed interest in breaking the cycle of disadvantage. At this point, we must deal with the reality of the large number of infants and young children who enter the foster-care system and who stay for substantial periods of time. This situation represents an opportunity for professionals and foster parents alike to play a crucial role in changing the potentially adverse course of development for many children. It is an opportunity too important to be lost.     

Magnetic resonance microimaging for noninvasive quantification of myocardial function and mass in the mouse

The purpose of this work was to develop high-resolution cardiac magnetic resonance imaging techniques for the in vivo mouse model for quantification of myocardial function and mass. Eight male mice were investigated on a 7-Tesla MRI scanner. High-quality images in multiple short axis slices (in-plane resolution 117 μm², slice thickness 1 mm) were acquired with an ECG-gated cine sequence. Left ventricular end-diastolic and end-systolic volumes and mass were calculated from segmented slice volumes. There was precise agreement of left ventricular mass determined ex vivo and by MRI. lntraobserver (5%) and interobserver (5%) variability of in vivo MR measurements were low.