The influence of sex on the relationship between heart rate recovery and other cardiovascular risk factors in apparently healthy subjects.

Heart rate recovery (HRR) is an important indicator of cardiovascular health. The purpose of the present investigation is to examine the influence of sex on the relationship between HRR and other markers of cardiovascular health. Two hundred and seventy-five apparently healthy subjects participated in this study. Subjects underwent cardiopulmonary exercise testing (outcome measures: VO(2max) and HRR 1 and 2 min into recovery), lipid analysis, measurement of resting systolic and diastolic blood pressure and measurement of aortic wave velocity (AWV in m/s) via magnetic resonance. HRR both at 1 min (HRR(1)) and at 2 min (HRR(2)) were higher in males. In general, the correlation between HRR(1) and other measures of interest was weaker than that found with HRR(2) in both male and female subjects. With respect to HRR(2), the relationship with other measures of interest was stronger in the female subgroup. Specific to arterial stiffness, the correlation between HRR(2) and AWV was -0.33 and -0.46 (P<0.001 for both) in male and female subgroups, respectively. The results of the present study indicate that both gender and the timing of HRR measurement influence its relationship with other important cardiovascular risk factors.

Loss of hepatic autoregulation after carbohydrate overfeeding in normal man.

To determine the effect of increased glycogen stores on hepatic carbohydrate metabolism, 15 nondiabetic volunteers were studied before and after 4 d of progressive overfeeding. Glucose production and gluconeogenesis were assessed with [2-3H] glucose and [6-14C] glucose (Study I, n = 6) or [3-3H] glucose and [U-14C]-alanine (Study II, n = 9) and substrate oxidation was determined by indirect calorimetry. Overfeeding was associated with significant (P < 0.01) increases in plasma glucose (4.97 +/- 0.10 to 5.09 +/- 0.11 mmol/liter), insulin (18.8 +/- 1.5 to 46.6 +/- 10.0 pmol/liter) and carbohydrate oxidation (4.7 +/- 1.4 to 18.0 +/- 1.5 mumol.kg-1.min-1) and a decrease in lipid oxidation (1.2 +/- 0.2 to 0.3 +/- 0.1 mumol.kg-1.min-1). Hepatic glucose output (HGO) increased in Study I (10.2 +/- 0.5 to 13.1 +/- 0.9 mumol.kg-1.min-1, P < 0.01) and Study II (11.17 +/- 0.67 to 13.33 +/- 0.83 mumol.kg-1.min-1, P < 0.01), and gluconeogenesis decreased (57.6 +/- 6.4 to 33.4 +/- 4.9 mumol/min, P < 0.01), indicating an increase in glycogenolysis. The increase in glycogenolysis was only partly compensated by an increase in glucose cycle activity (2.2 +/- 0.2 to 3.4 +/- 0.4 mumol.kg-1.min-1, P < 0.01) and the fall in gluconeogenesis, thus resulting in increased HGO. The suppression of gluconeogenesis despite increased lactate and alanine (glycerol was decreased) was associated with decreased free fatty acid (FFA) oxidation and negligible FFA enhanced gluconeogenesis. These studies suggest that increased liver glycogen stores alone can overwhelm normal intrahepatic mechanisms regulating carbohydrate metabolism resulting in increased HGO in nondiabetic man.

Pericardial adipose tissue and the metabolic syndrome is increased in patients with chronic major depressive disorder compared to acute depression and controls.

OBJECTIVE: Major depressive disorder (MDD) is associated with an estimated fourfold risk for premature death, largely attributed to cardiovascular disorders. Pericardial adipose tissue (PAT), a fat compartment surrounding the heart, has been implicated in the development of coronary artery disease. An unanswered question is whether people with chronic MDD are more likely to have elevated PAT volumes versus acute MDD and controls (CTRL). METHODS: The study group consists of sixteen patients with chronic MDD, thirty-four patients with acute MDD, and twenty-five CTRL. PAT and adrenal gland volume were measured by magnetic resonance tomography. Additional measures comprised factors of the metabolic syndrome, cortisol, relative insulin resistance, and pro-inflammatory cytokines (interleukin-6; IL-6 and tumor necrosis factor-α, TNF-α). RESULTS: PAT volumes were significantly increased in patients with chronic MDD>patients with acute MDD>CTRL. Adrenal gland volume was slightly enlarged in patients with chronic MDD>acute MDD>CTRL, although this difference failed to reach significance. The PAT volume was correlated with adrenal gland volume, and cortisol concentrations were correlated with depression severity, measured by BDI-2 and MADRS. Group differences were found concerning the rate of the metabolic syndrome, being most frequent in chronic MDD>acute MDD>CTRL. Further findings comprised increased fasting cortisol, increased TNF-α concentration, and decreased physical activity level in MDD compared to CTRL. CONCLUSION: Our results extend the existing literature in demonstrating that patients with chronic MDD have the highest risk for developing cardiovascular disorders, indicated by the highest PAT volume and prevalence of metabolic syndrome. The correlation of PAT with adrenal gland volume underscores the role of the hypothalamus-pituitary-adrenal system as mediator for body-composition changes. Metabolic monitoring, health advices and motivation for the improvement of physical fitness may be recommended in depressed patients, in particular in chronic depression.

Evidence for dual control mechanism regulating hepatic glucose output in nondiabetic men.

We previously reported a fall in hepatic glucose output (HGO) during sleep accompanied by reductions in glucose utilization (Rd) and free fatty acids (FFAs). This study was undertaken to determine the potential role of changes in Rd and FFA on HGO in nondiabetic men. To determine if the fall in HGO during sleep could be reversed by FFA elevation, seven nondiabetic men underwent [3-3H]glucose infusions from 2200 to 0800, with heparin (90 mU.kg-1.min-1) added at 0200. Glucose appearance (Ra) fell from 11.7 +/- 1.1 at 2430 to 8.9 +/- 0.8 mumol.kg-1.min-1 (P less than 0.05) at 0200. The fall in Ra was associated with decreases in FFA (0.57 +/- 0.10 to 0.48 +/- 0.07 mM) and glycerol (0.08 +/- 0.01 to 0.06 +/- 0.01 mM). Infusion of heparin significantly increased FFA and glycerol (1.09 +/- 0.21 and 0.11 +/- 0.01 mM, respectively, P less than 0.01) and resulted in a significant fall in plasma alanine, suggesting that gluconeogenesis had been increased. However, rates of glucose turnover were indistinguishable from overnight studies without heparin. In additional studies (n = 6), intralipid and heparin-induced FFA elevation (from 0.61 +/- 0.07 to 0.95 +/- 0.05 mM, P less than 0.01) stimulated gluconeogenesis ([U-14C]alanine to glucose) twofold (188 +/- 22% increase compared to 114 +/- 6% in saline control studies, P less than 0.01). However, despite increasing gluconeogenesis, overall HGO did not change (10.6 +/- 0.5 vs. 10.7 +/- 0.6 mumol.kg-1.min-1) during lipid infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired modulation of hepatic glucose output overnight after a 72-h fast in normal man.

We have previously reported a 25% fall in glucose utilization (Rd) and glucose production (Ra) in normal volunteers during an overnight fast, when glycogenolysis accounts for approximately 70% of hepatic glucose output (HGO). This reduction in Ra and Rd was positively correlated with reductions in glycerol and FFA. To determine if a similar fall in HGO occurs after a prolonged fast when HGO depends solely upon gluconeogenesis, seven normal male volunteers were fasted for 72 h. Glucose kinetics were then assessed overnight using a [3-3H]glucose infusion from 2200-0800 h. Plasma glucose (3.6 +/- 0.1 mM), immunoreactive insulin (2.7 +/- 0.4 mU/L), C-peptide (0.22 +/- 0.03 nmol/l), Rd (1.30 +/- 0.03 mg/kg.min), and Ra (1.28 +/- 0.03 mg/kg.min) were suppressed, and plasma glucagon (98.8 +/- 13.2 pmol/L) was elevated compared to values obtained during the overnight fast, but none of these parameters changed overnight after the 3-day fast. Plasma lactate (0.98 +/- 0.09 mmol/L) and alanine (0.18 +/- 0.03 mmol/L) levels were also unchanged throughout the night. Plasma glycerol (0.14 +/- 0.03 mmol/L) and FFA (0.98 +/- 0.07 mmol/L) were significantly elevated compared to values during the overnight fast, but failed to fall during the study as had been observed during a 14-h fast. We conclude that the modulation of HGO observed during an overnight fast does not occur during prolonged fasting. The lack of nocturnal modulation of HGO when plasma FFA and glycerol levels are fixed at elevated concentrations supports a role of FFA and/or glycerol in the modulation of HGO during an overnight fast.

Improved control of asthma in the office setting. A large-scale study of once-daily evening doses of theophylline.

A large-scale, multi-investigator open evaluation compared a once-daily regimen of controlled-release theophylline (Uniphyl tablets) with previous twice- or thrice-daily methylxanthine regimens. Three hundred asthmatic patients, 78 percent prone to nocturnal episodes during prior therapy, completed the investigation. Eighty-two percent of the patients were treated for moderate or severe disease. After a one-week evaluation of baseline theophylline therapy (with adjunctive medication), the patients substituted evening doses of the once-daily drug in approximate milligram-for-milligram equivalent doses. Concomitant medications were allowed as before. Nighttime and morning asthma control improved significantly without deterioration in the evening, and without increased side effects. Once-daily therapy resulted in markedly fewer night awakenings involving inhaler use (p less than 0.01), and near 60 percent reductions in the number of patients with nighttime or early morning exacerbations (p less than 0.01). Control of morning chest tightness, wheeze, and dyspnea improved significantly (p less than 0.01), and patients' as well as investigators' global evaluations favored once-daily treatment (p less than 0.01). Morning peak expiratory flow rates improved both at home (p less than 0.01) and at the office (p = 0.05). The forced expiratory volume in one second at the office increased modestly in the entire group. It is concluded that Uniphyl is effective and well tolerated when administered in once-daily evening doses.

Accelerated decline in hepatic glucose production during fasting in normal women compared with men.

Plasma glucose values have been reported to be lower in women than in men after a 72-hour fast. However, a comparison of glucose kinetics in fasting men and women has not been described. Therefore, five normal men and five normal women underwent sequential 3-3H-glucose infusions after both a 14- and a 64-hour fast. Plasma glucose levels fell similarly during the fast in men (5.23 +/- 0.03 v 3.96 +/- 0.14 mmol/L, P less than .01) and women (4.84 +/- 0.14 v 3.65 +/- 0.25 mmol/L, P less than .01). The fall in plasma glucose was associated with a significantly greater fall in glucose appearance (Ra) in women compared with men (P less than .05). Ra fell 15.8% +/- 3.0% in men (2.11 +/- 0.24 to 1.79 +/- 0.24 mg.kg-1.min-1, P less than .01) and 24.6% +/- 1.4% in women (2.22 +/- 0.17 to 1.67 +/- 0.12 mg.kg-1.min-1, P less than .001). During the fast, plasma glycerol, free fatty acids (FFA), and beta-hydroxybutyrate levels rose significantly and plasma alanine fell significantly in both sexes. Plasma glycerol levels were significantly higher in women compared with men after fasting (0.16 +/- 0.01 v 0.11 +/- 0.02 mmol/L, P less than .05). In addition, the transition from ambulation to bed rest demonstrated unexpected sex-related differences in glucose homeostasis after the 64-hour fast. During the two-hour equilibration period required for glucose kinetic studies (subjects reclining), significant decrements in glucose, FFA, and lactate were observed in the 64-hour fasted women but not in the men.(ABSTRACT TRUNCATED AT 250 WORDS)

Synthesis, photochemistry and application of (7-methoxycoumarin-4-yl)methyl-caged 8-bromoadenosine cyclic 3',5'-monophosphate and 8-bromoguanosine cyclic 3',5'-monophosphate photolyzed in the nanosecond time region.

New caged derivatives of hydrolysis-resistant 8-bromoadenosine cyclic 3',5'-monophosphate (8-Br-cAMP) and 8-bromoguanosine cyclic 3',5'-monophosphate (8-Br-cGMP) are described. The compounds are the axial and equatorial isomers of the (7-methoxycoumarin-4-yl)methyl (MCM) esters of cyclic nucleotides. Synthesis is accomplished by treatment of 4-bromomethyl-7-methoxycoumarin with the tetra-n-butylammonium salts of the 8-bromo-substituted cyclic nucleotides or with the free acids of 8-Br-cAMP and 8-Br-cGMP in the presence of silver(I) oxide. MCM-caged 8-Br-cAMP and MCM-caged 8-Br-cGMP liberate 8-Br-cAMP and 8-Br-cGMP during irradiation with ultraviolet light within a few nanoseconds. They show favorable absorption properties and quantum yields and are resistant to hydrolysis in aqueous buffer solutions. The moderate fluorescence properties of the caged compounds in comparison with the strongly fluorescent 4-hydroxymethyl-7-methoxycoumarin (MCM-OH) photoproduct allow the indirect estimation of the amount of photolytically released cyclic nucleotides in aqueous buffer solutions using fluorescence measurements. Their usefulness for physiological studies has been examined in a mammalian cell line expressing the cyclic nucleotide-gated ion channel of bovine olfactory sensory neurons using the patch-clamp technique and confocal laser scanning microscopy. The caged compounds serve as efficient and rapid intracellular sources of 8-Br-cAMP and 8-Br-cGMP. However, at least in HEK 293 cells, fluorescence signals cannot be used to monitor the photolysis of MCM-caged 8-Br-cAMP and 8-Br-cGMP, due to quenching of the fluorescence of MCM-OH.

Forecasts of preserved teeth and denture wearers among Danish adults early in the next century.

To assist in the planning of oral health services, forecasts were made and goals specified with regard to the numbers of preserved teeth and subjects wearing full or partial dentures among Danish adults in 1992 and 2002. Forecasting was based on existing data, viz. a survey in 1982, including clinical examination, of a representative sample of 20-80-yr-olds (n = 2548), on register data from the National Health Insurance, and survival rates. By combining information from these sources, an increase was estimated in number of preserved teeth among 20-99-yr-olds from 68 million in 1982 to 82 and 92 million in 1992 and 2002, respectively. Correspondingly, a 28% increase in the mean number of remaining teeth was proposed as a goal for the year 2002. A decrease was estimated in the number of denture wearers, from 1.4 million in 1982 to 1.07 and 0.74 million in 1992 and 2002, respectively. The corresponding goal was specified as a 50% reduction in the proportion of denture wearers in 2002. In the middle aged and older part of the population the increasing number of remaining teeth may be expected to imply considerable needs for professional care even in the beginning of the next century.

Orthodontic treatment priorities in the Danish Child Dental Health Services.

In 1980, the population of Danish schoolchildren in grade 9 formed the first cohort which, throughout all school grades, had been covered by the Child Dental Health Services, including free orthodontic care. National statistics on prevalence of malocclusion for this cohort of about 60 000 children in grades 3, 6, and 9 (approximate ages: 9, 12, and 15 years) were compared with corresponding frequencies in a population of schoolchildren in the 1960s among whom orthodontic treatment was rare. From the comparison it is inferred that treatment priority, based on professionally defined need, had been given to occlusal anomalies of the incisor segment, transverse anomalies of the lateral segments, and crowding.

Caries among Danish schoolchildren in birth-cohorts 1950-78.

Data on caries prevalence are reported from 8- and 16-yr-old children living in a Danish community which established the Public Child Dental Health Service in 1957. Every fourth birth-cohort from 1950 through 1970 was followed longitudinally. In the 8-yr-olds, caries prevalence decreased in the primary dentition from 17 to 3 dmfs and in the permanent dentition from 3.4 to 0.3 DMFS over a 28-yr period. Among the 16-yr-olds, a reduction was observed from 16.4 to 5.1 DMFS over 20 yr. Time trends in the decreasing caries prevalence are related to various organizational events and preventive measures. Moreover, the possible influence of general changes in living conditions and health behavior is pointed out.

A 15-year follow-up study of 30-year-old Danes with regard to orthodontic treatment experience and perceived need for treatment in a region without organized orthodontic care.

It was the aim to study orthodontic treatment experience and past and present perceived need for treatment in 30-year-old Danes who, at adolescence, had no access to organized orthodontic care. In order to identify the malocclusion traits which elicited treatment or need for treatment, the findings were related to the occurrence of various traits which had been registered in the same individuals 15 years earlier. From questionnaires (response rate 86%, n = 841) it appeared that 10% had received treatment and 20% perceived need for treatment either in childhood or at present. At adolescence, the subjects who had subsequently received treatment, displayed relatively high frequencies of ectopic eruption, anterior cross-bite, extreme maxillary overjet, deep bite, and crowding; among those who perceived need for treatment, extreme maxillary overjet, mandibular overjet and crowding were relatively prevalent.

Changes in prevalence of approximal caries in 17-year-olds and related restorative treatment strategies over a 6-year period.

Two cohorts of 17-yr-olds treated in a municipal child dental service in 1978-79 and 1984-85 had bitewing radiographs taken at the examination before the last course of treatment in the service. All radiographs were read by one examiner, who did not know to which cohort the individual belonged. The subsequent treatment was recorded from the treatment records by another examiner, who was unaware of the results of the radiographic examination. According to radiographic scores, the proportion of decayed or filled (DFS) approximal surfaces had decreased from 23.2% to 17.4% during the period (difference: 25%). The proportion of unfilled surfaces which were decayed (DS) had remained almost constant, while 9.6% of the surfaces were filled (FS) in 1978-79 compared to 3.1% in 1984-85 (difference: 68%). Thus, in spite of a 25% decrease in total caries experience (DFS), a reduction of 68% would be claimed if fillings (FS) were interpreted as expression of disease prevalence. The risk of an approximal surface being filled decreased to about one fifth from 1978-79 to 1984-85, and the risk of being filled was nearly three times as high for approximal surfaces of children who already had approximal fillings at the time of examination. Thus, both the year of examination and the subject's previously received treatment seemed to influence the treatment strategy of the dentist.

Timing of permanent tooth emergence in two Greenland Eskimo populations.

Mean times of emergence of the permanent teeth (except the first and third molars and mandibular central incisors) were studied cross-sectionally in an unmixed East Greenland population in 1957 and in present West Greenland Eskimo children. In spite of differences in racial and environmental conditions, practically no difference was found between the two samples in the timing of dental development in general, taking into account the average difference in emergence times of the individual teeth. Both samples showed advanced dental development in comparison with two unmixed Caucasoid and two unmixed Mongoloid populations. The mutual similarity in timing of tooth emergence between the East and West Greenland Eskimo children considerably greater than the similarity between each of the Eskimo samples and any of the other four populations.

Effect of separate malocclusion traits on concern for dental appearance.

Effects of separate traits of malocclusion on concern for dental appearance were isolated by means of multiple regression analysis in a 15-yr follow-up study of 30-yr-old Danes. On the basis of questionnaires (response rate 86%, n = 841), the dependent "concern-for-dental-appearance" variable was constructed from the respondents' replies about recalled perceptions and societal reactions concerning their dental appearance at the time of adolescence. In the same individuals, separate traits of malocclusion had been recorded clinically 15 yr earlier. These traits were inserted as independent dummy variables into the regression model. In both sexes the closest relationship with the dependent variable was displayed by the most conspicuous traits in the anterior region of the dentition. Some traits showed significant associations only in women, whose regression coefficients were, in general, higher than those of men. About half of the variation in the dependent variable was explained by the model.

Estimates of orthodontic treatment need in Danish schoolchildren.

Orthodontic treatment need has been assessed on the basis of complete orthodontic records in a random sample of 293 Danish children aged 13-17 years by a group of postgraduate orthodontic students and by three orthodontists. The estimates of treatment need ranged from 45% to 61%. Interexaminer agreement in pairs was observed in 77%-92% (mean 83%) of the cases. Uniformity in four individual assessments was reached in 69% of the cases: 38% were considered in need of treatment and 31% were considered not to present such need; conversely, 31% gave rise to disagreement. It is argued that, at present, the orthodontist's subjective estimate of treatment need probably constitutes a more realistic approach to the problem of assigning treatment priority than the various indices of malocclusion.

Meteorological influences on swarm emergence in honey bees (Hymenoptera: Apidae) as detected by crowdsourcing.

A crowdsourced dataset of 1,335 honey bee (Apis mellifera L.) swarm events in Germany in 2011 was created by beekeepers, public institutions, and members of the public and analyzed with respect to prevailing weather. The emergence of swarms appeared to be influenced by temperature and rainfall. On successive warm days in May the number of swarming events increased noticeably, but during a mid-month frost event the number of swarming events dropped markedly. Swarming events also occurred only rarely on rainy days. This study showed how crowdsourcing can be used to generate large, useful, phenological datasets.