Identification of caries risk factors in toddlers

The purpose of this study was to identify risk factors to predict caries progression in toddlers in primary-healthcare settings for the cost-effective targeting of preventive and referral strategies. We examined 329 children (26 ± 6 mos old) twice, one year apart, in Indiana, USA. A 107-item structured interview was used to collect information from the primary caregiver and child on factors/beliefs/perceptions/behaviors that could affect caries development, transmission of bacteria, medical-dental health, and access to care. Bacterial levels, gingivitis, dental plaque, and caries experience were assessed. Multiple-variable logistic regression models of caries progression toward cavitation included family caries experience, transmission-related behaviors, dietary factors, health beliefs, and lower income, but differed in selected predictors/predictive power by race/ethnicity. Addition of clinical variables did not significantly improve the prediction.     

Chanzyme TRPM7 Mediates the Ca2+ Influx Essential for Lipopolysaccharide-Induced Toll-Like Receptor 4 Endocytosis and Macrophage Activation

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Deficient adenylate cyclase regulatory protein in renal membranes from a patient with pseudohypoparathyroidism

Recent studies have established that some patients with pseudohypoparathyroidism have a deficiency of the adenylate cyclase regulatory protein (the G unit) in plasma membranes from erythrocytes, platelets, and fibroblasts. We have directly measured the activity of the G unit in renal membranes from a patient with pseudohypoparathyroidism who, in addition to parathyroid hormone resistance, has resistance to thyrotropin and gonadotropins. Erythrocyte membrane G unit activity was 57% that of control erythrocyte membranes. Lubrol PX extracts of renal membranes had only 30% of the G unit activity of control renal membrane extracts, whether assayed with sodium fluoride or guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S). In cholate extracts, the G unit activity was 37 and 48% of control with fluoride or GTP-gamma-S, respectively. Cholera toxin-dependent incorporation of [32P]ADP-ribose into the 42,000-Mr subunit of the G unit was decreased in renal membranes from the patient compared with control renal membranes. The data demonstrate that the membrane G unit deficiency in pseudohypoparathyroidism extends to the cells of a clinically relevant parathyroid hormone target tissue.     

Deficient guanine nucleotide regulatory unit activity in cultured fibroblast membranes from patients with pseudohypoparathyroidism type I. A cause of impaired synthesis of 3'',5''-cyclic AMP by intact and broken cells

Deficient activity of the guanine nucleotide regulatory protein (G unit), an integral component of the membrane-bound adenylate cyclase complex, has been implicated as the biochemical lesion in many patients with pseudohypoparathyroidism (PHP) type I. In addition to renal resistance to parathyroid hormone in this disorder, there is decreased responsiveness of diverse tissues to hormones that act via 3',5'-cyclic AMP (cAMP). To assess whether a deficiency of G units could account for impaired adenylate cyclase activity, we studied cAMP production in intact cultured fibroblasts and fibroblast plasma membranes from five patients with PHP in response to several activators of adenylate cyclase.

The number of G units in PHP fibroblast membranes, measured by cholera toxin-dependent [³²P]ADP ribosylation of G-unit peptides, as well as the G-unit activity, determined by the ability of detergent extracts to reconstitute adenylate cyclase activity in G-unit-deficient S49 CYC^- membranes, were found to be markedly reduced compared with control membranes (43 and 40%, respectively), The activation of fibroblast membrane adenylate cyclase by effectors that act directly through the G unit (guanosine triphosphate, guanosine 5'-0-[3-thiotriphosphate] [GTP-γ-S], NaF) was significantly greater in control membranes than in membranes from patients with PHP. Moreover, we found that hormone (prostaglandin E₁) stimulated adenylate cyclase activity was also greater in control membranes than in PHP membranes. Neither the apparent affinity of membrane adenylate cyclase for GTP-γ-S (apparent K_m =5 X 10^-8 M) nor the rate of enzyme activation by GTP-γ-S was significantly different in fibroblast membranes from control subjects and patients with PHP. In contrast to the notable differences in hormone and G-unit-activated adenylate cyclase shown in fibroblast membranes from PHP patients and control subjects, the intrinsic catalytic activity of membranes, as determined by forskolin-stimulated adenylate cyclase, was not significantly different in the two groups.

Intact fibroblasts derived from patients with PHP accumulated significantly (P 0.001) less cAMP (46±21 pmol cAMP/mcg DNA, n = 5) than cells from normal individuals (170±51 pmol cAMP/mcg DNA, n = 11) when stimulated with PGE₁. PGE₁-stimulated accumulation of cAMP by intact fibroblast monolayers correlated closely with PGE₁ plus GTP-activated membrane adenylate cyclase activity in both patients and controls (r = 0.97, P < 0.001).

Our data show that, in patients with PHP, (a) fibroblast membranes show a decreased complement of G units, (b) membrane catalytic activity is normal, but adenylate cyclase activity is reduced when stimulated by hormone or by effectors which activate the G unit, (c) the ability of cells to accumulate cAMP in response to hormone stimulation is reduced, and (d) reduced membrane adenylate cyclase activity correlates well with impaired cellular cAMP synthesis. These results, taken together, indicate that a deficiency of G-unit activity can impair synthesis of cAMP by both intact and broken cells, and may explain the resistance of multiple tissues to hormones that act via cAMP observed in PHP.

     

Real-time continuous estimation of gas exchange by dual oximetry

We designed a ventilation-perfusion index (VQI) to estimate venous admixture (Q_sp/Q_t) in a real-time fashion by simultaneous pulse and pulmonary artery oximetry in 17 patients with acute respiratory failure. Changes in Q_sp/Q_t were produced by altering the level of continuous positive airway pressure. VQI correlated well with Q_sp/Q_t (r=0.78). This contrasts with the poor correlation found between Q_sp/Q_t and the commonly used oxygen tension based indices such as PaO₂/FIO₂ (r=-0.51), PaO₂/PAO₂ (r=-0.47), and PAO₂-PaO₂ (r=0.23). The use of dual oximetry to derive a VQI appears to be a reliable and accurate method for real-time assessment of pulmonary gas exchange in patients with acute respiratory failure.     

An exploratory survey into primary care nurses and dementia care

This article introduces findings from the first phase of a randomized controlled trial of educational interventions in primary care. The focus of the article is the knowledge, attitudes and confidence of primary care nursing staff to the diagnosis and ongoing management of dementia. A total 78 nurses with a mean age of 46.4 years and a mean time since qualification of 23.0 years were recruited in 36 practices in central Scotland and in London. Disciplines represented by this sample were predominantly district nurses, health visitors, practice nurses and community staff nurses. Each practitioner was administered an extensive self-completion questionnaire before the educational interventions were introduced to measure baseline knowledge, confidence and perceived difficulties in dementia care management and attitudes. Results from the quiz indicate lower levels of knowledge about epidemiology and diagnosis, but slightly higher levels about management strategies. Self-reported ratings of confidence were also low and were directly related to ratings of difficulty in identifying dementia and dealing with coexisting behavioural and mental health problems. Lower scores on all domains were recorded for practice nurses than for district nurses or health visitors.     

Fructose:Glucose Ratios—A Study of Sugar Self-Administration and Associated Neural and Physiological Responses in the Rat

This study explored whether different ratios of fructose (F) and glucose (G) in sugar can engender significant differences in self-administration and associated neurobiological and physiological responses in male Sprague-Dawley rats. In Experiment 1, animals self-administered pellets containing 55% F + 45% G or 30% F + 70% G, and Fos immunoreactivity was assessed in hypothalamic regions regulating food intake and reward. In Experiment 2, rats self-administered solutions of 55% F + 42% G (high fructose corn syrup (HFCS)), 50% F + 50% G (sucrose) or saccharin, and mRNA of the dopamine 2 (D2R) and mu-opioid (MOR) receptor genes were assessed in striatal regions involved in addictive behaviors. Finally, in Experiment 3, rats self-administered HFCS and sucrose in their home cages, and hepatic fatty acids were quantified. It was found that higher fructose ratios engendered lower self-administration, lower Fos expression in the lateral hypothalamus/arcuate nucleus, reduced D2R and increased MOR mRNA in the dorsal striatum and nucleus accumbens core, respectively, as well as elevated omega-6 polyunsaturated fatty acids in the liver. These data indicate that a higher ratio of fructose may enhance the reinforcing effects of sugar and possibly lead to neurobiological and physiological alterations associated with addictive and metabolic disorders.     

Psychometric properties of the Quality of Life Inventory-Disability (QI-Disability) measure

Quality of Life Research - Children with intellectual disability encounter daily challenges beyond those captured in current quality of life measures. This study evaluated a new parent-report...