Recommendations for the classification of group A rotaviruses using all 11 genomic RNA segments

Recently, a classification system was proposed for rotaviruses in which all the 11 genomic RNA segments are used (Matthijnssens et al. in J Virol 82:3204-3219, 2008). Based on nucleotide identity cut-off percentages, different genotypes were defined for each genome segment. A nomenclature for the comparison of complete rotavirus genomes was considered in which the notations Gx-P[x]-Ix-Rx-Cx-Mx-Ax-Nx-Tx-Ex-Hx are used for the VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5/6 encoding genes, respectively. This classification system is an extension of the previously applied genotype-based system which made use of the rotavirus gene segments encoding VP4, VP7, VP6, and NSP4. In order to assign rotavirus strains to one of the established genotypes or a new genotype, a standard procedure is proposed in this report. As more human and animal rotavirus genomes will be completely sequenced, new genotypes for each of the 11 gene segments may be identified. A Rotavirus Classification Working Group (RCWG) including specialists in molecular virology, infectious diseases, epidemiology, and public health was formed, which can assist in the appropriate delineation of new genotypes, thus avoiding duplications and helping minimize errors. Scientists discovering a potentially new rotavirus genotype for any of the 11 gene segments are invited to send the novel sequence to the RCWG, where the sequence will be analyzed, and a new nomenclature will be advised as appropriate. The RCWG will update the list of classified strains regularly and make this accessible on a website. Close collaboration with the Study Group Reoviridae of the International Committee on the Taxonomy of Viruses will be maintained.     

TNF-alpha promoter polymorphisms in sudden infant death

Several studies indicate that the immune system is stimulated in sudden infant death syndrome (SIDS). Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that strongly affects the cytokine cascade. A genetic variant associated with high production of TNF-alpha may thus be of significance in the pathogenesis of SIDS. The purpose of the current study was to investigate possible relationships among the promoter polymorphisms -1031T/C, -857C/T, -308G/A, -244G/A, and -238G/A in the TNF-alpha gene and SIDS. The subjects investigated consisted of 148 SIDS cases, 56 borderline SIDS cases, 41 cases of infectious death, and 131 adult controls. When investigating each single nuclear polymorphism (SNP) separately, associations between -238GG and SIDS (p=0.022) and between -308GA and borderline SIDS (p=0.005) were found. There were no associations between any of the other SNPs investigated. Furthermore, a SNP profile was constructed by creating a genotype pattern from the investigated SNPs. Fifteen gene combinations were obtained, and 4 profiles had significantly different frequencies in SIDS cases and controls. The two SNP profiles -1031CT, -238GG, -857CC, -308GG and -1031TT, -238GG, -857CC, -308AA were found more often in SIDS and may thus be unfavorable. The findings add evidence to the theory that an unfavorable genetic profile in the TNF-alpha gene may be involved in SIDS by exposing the infant to both a high level of and prolonged exposure to TNF-alpha.     

Enhancing behavioral science education at the Ohio State University College of Medicine.

The social and behavioral sciences play key roles in patient health outcomes. Given this reality, successful development of social and behavioral science curricula in medical education is critically important to the quality of patients' lives and the effectiveness of health care delivery systems. The Institute of Medicine, in a recent report, recommended that medical schools enhance their curricula in these areas and identified four institutions as "exemplars" of social and behavioral science education. The authors describe an ongoing curriculum development and improvement process that produced one such exemplary program at The Ohio State University College of Medicine.The authors provide a historical perspective on behavioral science education, discuss issues that led to curricular change, and describe the principles and processes used to implement reform. Critical factors underlying positive change are addressed: increase active learning, recruit a core group of small-group facilitators who are primary care physicians, diversify teaching methods, support student-directed educational initiatives, enhance student-teacher relationships, centralize course administration, obtain funding, implement a faculty development program, and apply curriculum quality improvement methods. Outcome data from evaluations completed by both students and small-group physician faculty are presented, and future directions regarding further revision are outlined. The authors believe that the strategies they describe can be applied at other institutions and assist behavioral science educators who may experience the challenges typically encountered in this important field of medical education.     

Mast Cell Adenosine Induced Calcium Mobilization Via Gi3 and Gq Proteins

Adenosine is an important mediator of mast cell secretory responses. Adenosine appears to act through one or more adenosine receptor subtypes to activate several signal transduction pathways; however, the specific mechanisms involved are not clearly defined. We studied the pathways involved in adenosine receptor-mediated calcium fluxes in RBL-2H3 cells, a mucosal mast cell-like line. The role of endogenous heterotrimeric G proteins in adenosine mediated calcium mobilization was investigated by microinjection of inhibitory antibodies that block specific G protein subtype function. The calcium transients associated with adenosine and antigen stimulation were compared in noninjected cells and cells that were microinjected with affinity purified neutralizing antibodies to the subunits of G_i3, G_q, or G_s. The percentage of cells responding to adenosine was decreased in the presence of antibodies to G_i3 and G_q, but not G_s. Pertussis toxin decreased the percentage of cells responding to adenosine, but not antigen. These studies demonstrated a functional requirement for the pertussis toxin sensitive G_i3 protein and the pertussis toxin insensitive G_q protein in adenosine mediated calcium mobilization in mast cells.     

Responses of plasma glutamine, free tryptophan and branched-chain amino acids to prolonged exercise after a regime designed to reduce muscle glycogen

Prolonged exercise can elicit a reduction in the plasma glutamine concentration and an increase in the plasma concentration ratio of free tryptophan (FTrp) to branched-chain amino acids (BCAA). The purpose of this investigation was to study the effects of a 60-min bout of vigorous treadmill running with dietary manipulation on plasma concentrations of glutamine, FTrp and BCAA after an exercise and diet regime designed to reduce muscle glycogen. Seven male distance runners [mean (SD) age: 29.3?(2.1) years; ˙VO _2max : 62.7?(3.3) ml?·?kg^?1?·?min^?1] acted as subjects. Each undertook a regime designed to reduce muscle glycogen, then performed a 60-min treadmill run (75% ˙VO _2max ) under two dietary conditions: after a 14-h fast (?fasted) and after ingestion of a high carbohydrate meal (30?kJ?·?kg^?1: 80% carbohydrate, 10% protein, 10% fat) 3?h before running (?fed). Plasma concentrations of glutamine, FTrp, BCAA, free fatty acids (FFA), glycerol and glucose were measured 5?min before and 5?min after the run, under each dietary condition. Plasma glutamine did not change in response to exercise when fasted (P > 0.05), but increased when fed (P = 0.007). Plasma FTrp increased under both dietary conditions (P < 0.001), but the magnitude of this increase was greater when fasted than when fed (P < 0.001). Plasma BCAA did not change under either dietary condition (P < 0.05). Increases in the plasma FTrp/BCAA ratio reflected increases in plasma FFA and glycerol concentrations (P < 0.001; both dietary conditions) and these changes were all greater under fasted conditions when a fall in blood glucose concentration was observed (P = 0.007). These data emphasise the importance of dietary carbohydrate intake between repeated bouts of prolonged exercise on responses of plasma glutamine, FTrp and BCAA during subsequent exercise.     

Physiological measures of mother–infant interactional synchrony

Mother–infant interactional synchrony has been hypothesized to be crucial for the development of many key neurodevelopmental behaviors in infants, including speech and language. Assessing synchrony is challenging because many interactive behaviors may be subtlety, if at all, observable in overt behaviors. Physiological measures, therefore, may provide valuable physiological/biological markers of mother–infant synchrony. We have developed a multilevel measurement platform to assess physiological synchrony, attention, and vocal congruency during dynamic face-to-face mother–infant interactions. The present investigation was designed to provide preliminary data on its application in a group of 10 mother–infant dyads (20 subjects) ranging in age from 7 to 8.5 months at the time of the experimentation. Respiratory kinematics, heart rate, and vocalization were recorded simultaneously from mothers and infants during nonstructured, face-to-face interactions. Novel statistical methods were used to identify reliable moments of synchrony from cross-correlated, mother–infant respiration and to tag infant attention from heart rate deceleration. Results revealed that attention, vocal contingency, and respiratory synchrony are temporally clustered within the dyad interaction. This temporal alignment is consistent with the notion that biological synchrony provides a supportive platform for infant attention and mother–infant contingent vocalization.     

Genetic basis of neurodevelopmental disorders in 103 Jordanian families

We recruited 103 families from Jordan with neurodevelopmental disorders (NDD) and patterns of inheritance mostly suggestive of autosomal recessive inheritance. In each family, we investigated at least one affected individual using exome sequencing and an in-house diagnostic variant interpretation pipeline including a search for copy number variation. This approach led us to identify the likely molecular defect in established disease genes in 37 families. We could identify 25 pathogenic nonsense and 11 missense variants as well as 3 pathogenic copy number variants and 1 repeat expansion. Notably, 11 of the disease-causal variants occurred de novo. In addition, we prioritized a homozygous frameshift variant in PUS3 in two sisters with intellectual disability. To our knowledge, PUS3 has been postulated only recently as a candidate disease gene for intellectual disability in a single family with three affected siblings. Our findings provide additional evidence to establish loss of PUS3 function as a cause of intellectual disability.     

Protein kinase inhibitors substantially improve the physical detection of T-cells with peptide-MHC tetramers

Flow cytometry with fluorochrome-conjugated peptide-major histocompatibility complex (pMHC) tetramers has transformed the study of antigen-specific T-cells by enabling their visualization, enumeration, phenotypic characterization and isolation from ex vivo samples. Here, we demonstrate that the reversible protein kinase inhibitor (PKI) dasatinib improves the staining intensity of human (CD8+ and CD4+) and murine T-cells without concomitant increases in background staining. Dasatinib enhances the capture of cognate pMHC tetramers from solution and produces higher intensity staining at lower pMHC concentrations. Furthermore, dasatinib reduces pMHC tetramer-induced cell death and substantially lowers the T-cell receptor (TCR)/pMHC interaction affinity threshold required for cell staining. Accordingly, dasatinib permits the identification of T-cells with very low affinity TCR/pMHC interactions, such as those that typically predominate in tumour-specific responses and autoimmune conditions that are not amenable to detection by current technology.     

Patterns and changes in prescriber attitudes toward PDA prescription-assistive technology

Context

Medication error prevention is a priority for the U.S. healthcare system in the 21st century. Use of technology is considered by some as critical to achieve this goal. Knowledge of the attitudinal barriers to such adoption, however, is limited.

Objective

To determine the attitudes of frontline prescriber clinicians towards technology in general, and PDAs specifically, before and after introduction of a PDA in the clinical setting of medication prescribing.

Design

A pre- and post-intervention web-based survey, 12-14 months apart.

Setting

Academic tertiary care children's hospital.

Participants

Total of 244 prescriber clinicians.

Intervention

Distribution of a PDA with pediatric-specific medication prescribing information after completion of an on-line medication safety certification and other safety focused educational sessions.

Main outcome measures

Ratings (5-point Likert scale) reflecting perceptions and attitudes towards technology in general and technology in medical settings along with self-reported usage of the PDA for Rx.

Results

Early Adopters and Late Adopters were identified statistically, and the group membership reflected their prior exposure to and ownership of other technologies. Early Adopters tended to be younger and less experienced clinically (e.g., residents) and more frequent owners and users of technology. Early Adopters expressed significantly more favorable attitudes toward technology and PDAs on both pre- to post-intervention survey occasions. They also utilized the PDA for Rx more often than LAs. Interestingly, PDA use for Early Adopters was based on its ease of use, while PDA use among later adopters was based on its clinical usefulness.

Conclusions

Provision of point of care information using PDAs and a user-friendly, pediatric-specific medication information software package did not positively affect the attitudes of prescriber clinicians among those already favorable toward technology. However, a significant change was found among those with initially less favorable attitudes. Organizations need to understand the nature of both Early and Late Adopters and plan appropriately for managing the respective needs and expectations when potentially beneficial technologies are introduced. In order to ensure the success of an implementation, the training and supportive interventions need to be carefully designed and specifically catered to the personality-based outcome expectations of the prescriber.