Transdisciplinary unifying implications of circadian findings in the 1950s

A few puzzles relating to a small fraction of my endeavors in the 1950s are summarized herein, with answers to a few questions of the Editor-in-Chief, to suggest that the rules of variability in time complement the rules of genetics as a biological variability in space. I advocate to replace truisms such as a relative constancy or homeostasis, that have served bioscience very well for very long. They were never intended, however, to lower a curtain of ignorance over everyday physiology. In raising these curtains, we unveil a range of dynamics, resolvable in the data collection and as-one-goes analysis by computers built into smaller and smaller devices, for a continued self-surveillance of the normal and for an individualized detection of the abnormal. The current medical art based on spotchecks interpreted by reference to a time-unqualified normal range can become a science of time series with tests relating to the individual in inferential statistical terms. This is already doable for the case of blood pressure, but eventually should become possible for many other variables interpreted today only based on the quicksand of clinical trials on groups. These ignore individual differences and hence the individual's needs. Chronomics (mapping time structures) with the major aim of quantifying normalcy by dynamic reference values for detecting earliest risk elevation, also yields the dividend of allowing molecular biology to focus on the normal as well as on the grossly abnormal

Modified differentials and basic cohomology for Riemannian foliations

We define a new version of the exterior derivative on the basic forms of a Riemannian foliation to obtain a new form of basic cohomology that satisfies Poincar\'e duality in the transversally orientable case. We use this twisted basic cohomology to show relationships between curvature, tautness, and vanishing of the basic Euler characteristic and basic signature.Comment: 20 pages, references added, minor corrections mad

Chronobiology of high blood pressure

BIOCOS, the project aimed at studying BIOlogical systems in their COSmos, has obtained a great deal of expertise in the fields of blood pressure (BP) and heart rate (HR) monitoring and of marker rhythmometry for the purposes of screening, diagnosis, treatment, and prognosis. Prolonging the monitoring reduces the uncertainty in the estimation of circadian parameters; the current recommendation of BIOCOS requires monitoring for at least 7 days. The BIOCOS approach consists of a parametric and a non-parametric analysis of the data, in which the results from the individual subject are being compared with gender- and age-specified reference values in health. Chronobiological designs can offer important new information regarding the optimization of treatment by timing its administration as a function of circadian and other rhythms. New technological developments are needed to close the loop between the monitoring of blood pressure and the administration of antihypertensive drugs

Volcanoes: effusions and explosions. Interactive exhibits to understand how volcanoes work

The Educational & Outreach Group (EOG) of the Istituto Nazionale di Geofisica & Vulcanologia created a portable museum to provide educational opportunities in volcanology, volcanic risk and Earth science for students and visitors. The EOG developed this project for the "Festival della Scienza", organized in Genoa, Italy, in October - November, 2007, which was a parade of over 200 events, including scientific and technological exhibitions, workshops, meetings, lectures, books and video presentations. In this museum visitors can successively see many posters and movies and play with interactive exhibits. A little 3D-movie shows the Big Bang, the formation of Solar System and, in particular the formation of the Earth. Many interactive exhibits illustrate why, where and when earthquakes and volcanic eruptions occur around the world and allow to introduce the visitor to the plate tectonics theory. A 3D magnetic plate tectonic puzzle can be put down and reconstructed by visitors to understand the Earth’s surface configuration. Then two other 3D Earth models show what drives the plates and the inner Earth structure. An interactive program illustrates where and when earthquakes and volcanic eruptions occur in accelerated time on maps of various areas around the world. Playing with a block diagram it is possible to produce an earthquake along a 1 meter long strike slip fault in a destroying all the man-made constructions close to it. A little movie introduces to volcanoes’ world. Two small interactive exhibits allow visitors to understand the mechanism for the explosive and the effusive eruptions. Two other exciting interactive exhibits allow visitors to “create” two different eruptions: the explosive and the effusive ones. It is possible to get inside a volcano (a 2 meter high interactive exhibit) to attend an eruption from the magmatic chamber to the Earth surface. A big hall is completed dedicated to Italian volcanoes (Vesuvio, Campi Flegrei, Etna, Stromboli, Vulcano, Colli Albani); some of them are reproduced with 3D models or described by short movies. The museum finishes with the visit of the volcanic survey hall of Stromboli, seeing - in real time - seismic data, three different webcams, geochemical and strain data. The INGV Museum had remarkably successful, reaching more than 7,500 children and adults yet in 13 days, also thanks to 30 volcanologists as very special guides. The Educational & Outreach Group: M. Pignone, A. Tertulliani, M. De Lucia, M. Di Vito, P. Landi, P. Madonia, M. Martini, R. Nave, M. Neri, P. Scarlato, J. Taddeucci, R. Moschillo, S. Tarquini, G. Vilardo, A. Bonforte, L. Calderone, F. Cannavò, W. De Cesare, P. Ficeli, S. Inguaggiato, M. Mattia, G. Puglisi, S. Morici, D. Reitano, D. Richichi, G. Scarpato, B. Angioni, F. Di Laura, S. Palone, D. Riposat

Seasonal pattern of peptic ulcer hospitalizations: analysis of the hospital discharge data of the Emilia-Romagna region of Italy

BACKGROUND: Previous studies have reported seasonal variation in peptic ulcer disease (PUD), but few large-scale, population-based studies have been conducted. METHODS: To verify whether a seasonal variation in cases of PUD (either complicated or not complicated) requiring acute hospitalization exists, we assessed the database of hospital admissions of the region Emilia Romagna (RER), Italy, obtained from the Center for Health Statistics, between January 1998 and December 2005. Admissions were categorized by sex, age ( or = 75 yrs), site of PUD lesion (stomach or duodenum), main complication (hemorrhage or perforation), and final outcome (intended as fatal outcome: in-hospital death; nonfatal outcome: patient discharged alive). Temporal patterns in PUD admissions were assessed in two ways, considering a) total counts per single month and season, and b) prevalence proportion, such as the monthly prevalence of PUD admissions divided by the monthly prevalence of total hospital admissions, to assess if the temporal patterns in the raw data might be the consequence of seasonal and annual variations in hospital admissions per se in the region. For statistical analysis, the chi2 test for goodness of fit and inferential chronobiologic method (Cosinor and partial Fourier series) were used. RESULTS: Of the total sample of PUD patients (26,848 [16,795 males, age 65 +/- 16 yrs; 10,053 females, age 72 +/- 15 yrs, p or = 75 yrs of age. There were more cases of duodenal (DU). (89.8%) than gastric ulcer (GU) (3.6%), and there were 1,290 (4.8%) fatal events. Data by season showed a statistically difference with the lowest proportion of PUD hospital admissions in summer (23.3%) (p < 0.001), for total cases and rather all subgroups. Chronobiological analysis identified three major peaks of PUD hospitalizations (September-October, January-February, and April-May) for the whole sample (p = 0.035), and several subgroups, with nadir in July. Finally, analysis of the monthly prevalence proportions yielded a significant (p = 0.025) biphasic pattern with a main peak in August-September-October, and a secondary one in January-February. CONCLUSIONS: A seasonal variation in PUD hospitalization, characterized by three peaks of higher incidence (Autumn, Winter, and Spring) is observed. When data corrected by monthly admission proportions are analyzed, late summer-autumn and winter are confirmed as higher risk periods. The underlying pathophysiologic mechanisms are unknown, and need further studies. In subjects at higher risk, certain periods of the year could deserve an appropriate pharmacological protection to reduce the risk of PUD hospitalization

Altered time structure of neuro-endocrine-immune system function in lung cancer patients

<p>Abstract</p> <p>Background</p> <p>The onset and the development of neoplastic disease may be influenced by many physiological, biological and immunological factors. The nervous, endocrine and immune system might act as an integrated unit to mantain body defense against this pathological process and reciprocal influences have been evidenced among hypothalamus, pituitary, thyroid, adrenal, pineal gland and immune system. In this study we evaluated differences among healthy subjects and subjects suffering from lung cancer in the 24-hour secretory profile of melatonin, cortisol, TRH, TSH, FT4, GH, IGF-1 and IL-2 and circadian variations of lymphocyte subpopulations. </p> <p>Methods</p> <p>In ten healthy male volunteers (age range 45-66) and ten male patients with untreated non small cell lung cancer (age range 46-65) we measured melatonin, cortisol, TRH, TSH, FT4, GH, IGF-1 and IL-2 serum levels and percentages of lymphocyte subpopulations on blood samples collected every four hours for 24 hours. One-way ANOVA between the timepoints for each variable and each group was performed to look for a time-effect, the presence of circadian rhythmicity was evaluated, MESOR, amplitude and acrophase values, mean diurnal levels and mean nocturnal levels were compared.</p> <p>Results</p> <p>A clear circadian rhythm was validated in the control group for hormone serum level and for lymphocyte subsets variation. Melatonin, TRH, TSH, GH, CD3, CD4, HLA-DR, CD20 and CD25 expressing cells presented circadian rhythmicity with acrophase during the night. Cortisol, CD8, CD8^bright, CD8^dim, CD16, TcRδ1 and δTcS1 presented circadian rhythmicity with acrophase in the morning/at noon. FT4, IGF-1 and IL-2 variation did not show circadian rhythmicity. In lung cancer patients cortisol, TRH, TSH and GH serum level and all the lymphocyte subsubsets variation (except for CD4) showed loss of circadian rhythmicity. MESOR of cortisol, TRH, GH, IL-2 and CD16 was increased, whereas MESOR of TSH, IGF-1, CD8, CD8^bright, TcRδ1 and δTcS1 was decreased in cancer patients. The melatonin/cortisol mean nocturnal level ratio was decreased in cancer patients.</p> <p>Conclusion</p> <p>The altered secretion and loss of circadian rhythmicity of many studied factors observed in the subjects suffering from neoplastic disease may be expression of gradual alteration of the integrated function of the neuro-immune-endocrine system</p

The Role of Body Mass Index, Insulin, and Adiponectin in the Relation Between Fat Distribution and Bone Mineral Density

Despite the positive association between body mass index (BMI) and bone mineral density (BMD) and content (BMC), the role of fat distribution in BMD/BMC remains unclear. We examined relationships between BMD/BMC and various measurements of fat distribution and studied the role of BMI, insulin, and adiponectin in these relations. Using a cross-sectional investigation of 2631 participants from the Erasmus Rucphen Family study, we studied associations between BMD (using dual-energy X-ray absorptiometry (DXA]) at the hip, lumbar spine, total body (BMD and BMC), and fat distribution by the waist-to-hip ratio (WHR), waist-to-thigh ratio (WTR), and DXA-based trunk-to-leg fat ratio and android-to-gynoid fat ratio. Analyses were stratified by gender and median age (48.0 years in women and 49.2 years in men) and were performed with and without adjustment for BMI, fasting insulin, and adiponectin. Using linear regression (adjusting for age, height, smoking, and use of alcohol), most relationships between fat distribution and BMD and BMC were positive, except for WTR. After BMI adjustment, most correlations were negative except for trunk-to-leg fat ratio in both genders. No consistent influence of age or menopausal status was found. Insulin and adiponectin levels did not explain either positive or negative associations. In conclusion, positive associations between android fat distribution and BMD/BMC are explained by higher BMI but not by higher insulin and/or lower adiponectin levels. Inverse associations after adjustment for BMI suggest that android fat deposition as measured by the WHR, WTR, and DXA-based android-to-gynoid fat ratio is not beneficial and possibly even deleterious for bone