Hydration and Cognitive Function in Children

Adequate fluid intake is critical for survival. While adults are at liberty to drink fluids as wanted, children and infants are dependent upon caregivers for food and fluid. Children are at greater risk for dehydration than adults due to their higher surface-to-mass ratio. Additionally, children have different thirst sensitivities and body cooling mechanisms than adults. Children differ from adults in total body water content, and boys and girls differ in body water content with maturation. Research in young adults shows that mild dehydration corresponding to only 1% to 2% of body weight loss can lead to significant impairment in cognitive function. Dehydration in infants is associated with confusion, irritability, and lethargy; in children, it may produce decrements in cognitive performance.     

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Sans résumé     

A novel nucleotide-containing antigen for human blood γδ T lymphocytes

The stimulation of human γδ T cells by mycobacteria occurs through recognition of four distinct nonpeptide phosphorylated antigens termed TUBag1–4. Among these latter, TUBag4 has already been biochemically characterized as a γ-X derivative of 5′-deoxythymidine triphosphate (Constant, P., Davodeau, F., Peyrat, M. A., Poquet, Y., Puzo, G., Bonneville, M. and Fournié, J.-J., Science 1994. 264: 267). However, despite chemical synthesis of weakly stimulatory nucleotide-containing analogs, these mycobacterial compounds remained the sole nucleotide-containing antigens actually isolated from natural sources. Here, we present the complete isolation of the TUBag3 antigen from Mycobacterium fortuitum and demonstrate that this nonpeptide molecule contains a 5′-UTP nucleotide moiety. On selected Vγ9/Vδ2 clones, T cell responses can be triggered with nanomolar concentrations of TUBag3. Like crude mycobacterial extracts, this purified nucleotide conjugate elicits a strong polyclonal response of γδ PBL from healthy donors. Furthermore, we present evidence that this compound is distinct from the recently synthesized γ-isopentenyl 5′-UTP, a nucleotide conjugate of isopentenyl pyrophosphate that was found to be stimulatory for human γδ T cells (Tanaka, Y., Morita, C. T., Tanaka, Y., Nieves, E., Brenner, M. B. and Bloom, B. R., Nature 1995. 375: 155). Since it appears that both mycobacterial nucleotide antigens are molecules structurally related to peculiar precursors of nucleic acid synthesis, we propose that TUBag-reactive T cells might be specifically devoted to surveillance of proliferating cells.     

AMPK as a metabolic switch in rat muscle,liver and adipose tissue after exercise

An increasing body of evidence has revealed that activation of adenosine monophosphate (AMP)‐activated protein kinase (AMPK)‐activated protein kinase increases fatty acid oxidation by lowering the concentration of malonyl coenzyme A (CoA), an inhibitor of carnitine palmitoyl transferase 1. Studies carried out primarily in skeletal muscle suggest that AMPK modulates the concentration of malonyl CoA by concurrently phosphorylating and inhibiting acetyl CoA carboxylase (ACC), the rate limiting enzyme in malonyl CoA synthesis, and phosphorylating and activating malonyl CoA decarboxylase (MCD), an enzyme involved in its degradation. We have recently observed that AMPK and MCD activities are increased and ACC activity diminished in skeletal muscle, liver and, surprisingly, in adipose tissue 30 min following exercise (treadmill run) in normal rats. In liver and adipose tissue these changes were associated with a decrease in the activity of glycerol‐3‐phosphate acyltransferase (GPAT), which catalyses the first committed reaction in glycerolipid synthesis and, which like ACC, is phosphorylated and inhibited by AMPK. Similar changes in ACC, MCD and GPAT were observed following the administration of 5‐aminoimidazole 4‐carboxamide‐riboside (AICAR), further indicating that the exercise‐induced alterations in these enzymes were AMPK‐mediated. Conclusions: (1) AMPK plays a major role in regulating lipid metabolism in multiple tissues following exercise. (2) The net effect of its activation is to increase fatty acid oxidation and diminish glycerolipid synthesis. (3) The relevance of these findings to the regulation of muscle glycogen repletion in the post‐exercise state and to the demonstrated ability of AMPK activation to decrease adiposity and increase insulin sensitivity in rodents remains to be determined.     

Clinical effectiveness of a mite allergen-impermeable bed-covering system in asthmatic mite-sensitive patients

BACKGROUND: Exposure to allergens plays a role in the development of bronchial hyperresponsiveness and in the chronic inflammatory response seen in asthmatic patients. House dust mites (HDMs) are an important source of allergen. Reduction of these allergens might lead to better lung function and reduction of asthma symptoms. OBJECTIVE: The effect of HDM-impermeable covers on HDM allergen levels, peak flow values, and asthma symptoms were measured. Therefore a randomized clinical trial was carried out. METHODS: Fifty-two allergic asthmatic patients were randomly allocated to use the HDM-impermeable or placebo covers. During the study period, daily peak flow and asthma symptom scores were recorded. Dust samples were taken from the mattresses. RESULTS: We observed a significant reduction in HDM allergen levels on the mattresses after encasing them with HDM-impermeable covers (reduction of 87% of Der p 1 in micrograms per gram of dust; P <.001). Baseline symptoms were so low that no improvement could be established. Morning peak expiratory flow is significantly higher in the intervention group compared with that seen in the placebo group during the study period (beta=20.2; P <.01). CONCLUSIONS: HDM-impermeable covers significantly decreased the level of HDM allergens. Furthermore, morning peak flow was significantly increased during the intervention period. This study indicates that HDM allergen-avoidance measures might have beneficial effects on allergen reduction and asthma outcome.     

Are primed CD4+ T lymphocytes different from unprimed cells?

Primed and unprimed lymphocytes are usually classified as separate subsets of cells, based on phenotypic and functional distinctions. In the case of CD4⁺ T lymphocytes, primed cells are thought to proliferate more vigorously, quickly and easily, and to release a different profile of cytokines, than their naive equivalent. However, most of these data were obtained from studies in which populations of lymphocytes were compared before and after antigenic stimulation, and therefore did not distinguish between the effects resulting from the clonal expansion of specific precursor cells within such populations and those due to cell differentiation per se. We have investigated the contribution of precursor cell frequency to some of the functional changes observed in populations of CD4⁺ T cells following antigenic stimulation, using approaches in which antigen-specific precursor frequencies are high in both primary and secondary stimulations: mixed leukocyte reaction responses and cells from αβ T cell receptor transgenic mice. Our data suggest that when equivalent numbers of antigen-specific naive and previously primed CD4⁺ responder T cells are compared, there is no difference in their potency to proliferate but only the previously activated subset can generate cytokines such as interferon-γ.     

Maternal and neonatal outcome in pregnancies with no risk factors.

Between November 1979 and April 1984, 790 consecutive pregnant women who considered themselves as having a "normal" pregnancy were followed in private practice from 9 weeks' gestation until 6 weeks post partum. The women had no pre-existing disease or problem classified as a risk to the pregnancy at the time of their first visit, had a singleton pregnancy and gave birth at Notre-Dame Hospital, Montreal. Maternal complications occurred during the course of pregnancy in 181 women (23%). Complications were mostly related to obstetric conditions (10%), such as preterm labour, intrauterine growth retardation (IUGR) and antepartum hemorrhage, or to medical conditions (12%), the most prevalent of which was hypertension (77% of medical conditions). Neonatal complications occurred in 183 infants (23%). The corrected perinatal death rate was 2.5 per 1000. Prematurity, IUGR and dysmaturity/postmaturity accounted for nearly half of the complications. Hyperbilirubinemia occurred in 7% of the cases. Among women without any maternal complications during pregnancy, the frequency rate of neonatal complications was 19%, compared with 23% among the entire group of 790 women. Our results suggest that the absence of maternal complications does not protect the infant from a neonatal complication. Further refinement is needed to identify markers of obstetric, medical and neonatal complications in pregnancies with no risk factors.     

Testing a policy for skull radiography (and admission) following mild head injury

There has been, and continues to be, conflicting advice regarding skull radiography following an apparently uncomplicated head injury. Policies on admission are often ill defined. In 1983, representatives of the Royal College of Radiologists met neurosurgeons at a seminar in Harrogate organized by the DHSS and laid down clear, but little publicized, joint recommendations: "The Harrogate Criteria". The survey described here evaluated an existing liberal policy for skull radiography (and a loose policy for admissions) against these recommendations, and it was concluded that the number of patients having skull radiography (74% of head injury attenders) was excessive. Measured against the "Harrogate Criteria", requests for 36% of the adult and 47% of children's skull radiographs did not fulfil these criteria. As a corollary, it was also concluded that loose admissions policies could usefully be altered to comply more closely with the Harrogate recommendations. This would not necessarily reduce the numbers admitted, but would provide casualty officers with a framework on which to base this crucial aspect of clinical decision making, where presently there is often very little structure at all. The authors suggest that all the options have not been fully explored, and that a simple but important alteration to the Harrogate guidelines would provide an even closer link between policy on skull radiography and patient admission. Specifically, most patients who are to be admitted do not need skull radiographs.     

Vaccine-induced binding and neutralizing antibodies against Omicron 6 months after a homologous BNT162b2 booster

Evidence about the long-term persistence of the booster-mediated immunity against Omicron is mandatory for pandemic management and deployment of vaccination strategies. A total of 155 healthcare professionals (104 COVID-19 naive and 51 with a history of SARS-CoV-2 infection) received a homologous BNT162b2 booster. Binding antibodies against the spike protein and neutralizing antibodies against Omicron were measured at several time points before and up to 6 months after the booster. Geometric mean titers of measured antibodies were correlated to vaccine efficacy (VE) against symptomatic disease. Compared to the highest response, a significant 10.2- and 11.5-fold decrease in neutralizing titers was observed after 6 months in participants with and without history of SARS-CoV-2 infection. A corresponding 2.5- and 2.9-fold decrease in binding antibodies was observed. The estimated T_1/2 of neutralizing antibodies in participants with and without history of SARS-CoV-2 infection was 42 (95% confidence interval [CI]: 25–137) and 36 days (95% CI: 25–65). Estimated T_1/2 were longer for binding antibodies: 168 (95% CI: 116–303) and 139 days (95% CI: 113–180), respectively. Both binding and neutralizing antibodies were strongly correlated to VE (r = 0.83 and 0.89). However, binding and neutralizing antibodies were modestly correlated, and a high proportion of subjects (36.7%) with high binding antibody titers (i.e., >8434 BAU/ml) did not have neutralizing activity. A considerable decay of the humoral response was observed 6 months after the booster, and was strongly correlated with VE. Our study also shows that commercial assays available in clinical laboratories might require adaptation to better predict neutralization in the Omicron era.