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Beside the reversible t-time of physics is introduced an irreversible logarithmical tau-time as a second time. This time is determined by growth, vitality, and reliability of an organism. Using the tau-time it is possible to divide the lifespan of an organism into four parts. Each segment is of approximately the same duration, namely a quarter of the lifespan. There is an analogy between tau-time and physical entropy.
Red cells are replaced before they become senescent. It is probable that red cell destruction is controlled by a biologic clock, essentially independent of metabolism, rather than by metabolic failure. The appearance of neo-antigens on the external surface of the red cell could be this "clock."
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Bancroftian filariasis is spreading in towns of endemic areas in Recife, northeastern Brazil, where it is a major public health problem. This paper deals with the prevalence of microfilaraemia and filarial disease in two urban areas of Recife, studying their association with individual characteristics and variables related to the exposure to the vectors. The parasitologic survey was performed through a "door-to-door" census and microfilaraemia was examined by the thick-drop technique using 45 microliters of peripheral blood collected between 20:00 and 24:00 o'clock. 2,863 individuals aged between 5 and 65 years were interviewed and submitted to clinical examination. Males aged between 15 and 44 years old presented the greatest risk of being microfilaraemic. Microfilaraemia was also significantly associated with no use of bednet to sleep. The risk of being microfilaraemic was greater among those who had lived in the studied areas for more than 5 years. The overall disease prevalence was 6.3%. Males presented the greatest risk of developing acute disease. The risk of developing chronic manifestations was also greater among males and increased with age. We found no association between time of residence, bednet use, microfilaraemia and acute and chronic disease. We may conclude that in endemic areas there are subgroups of individuals who has a higher risk of being microfilariae carriers due to different behaviours in relation to vector contact.
This review provides evidence that the bioengineering community needs to develop cost-effective, fully unobtrusive, truly ambulatory instrumentation for the surveillance of blood pressure and heart rate. With available instrumentation, we document a disease risk syndrome, circadian blood pressure overswinging (CHAT, short for circadian hyper-amplitude-tension). Circadian hyper-amplitude-tension is defined as a week-long overall increase in the circadian amplitude or otherwise-measured circadian variability of blood pressure above a mapped threshold, corresponding to the upper 95% prediction limit of clinically healthy peers of the corresponding gender and age. A consistently reduced heart rate variability, gauged by a circadian standard deviation below the lower 5% prediction limit of peers of the corresponding gender and age, is an index of a separate yet additive major risk, a deficient heart rate variability (DHRV). The circadian amplitude, a measure of the extent of reproducible variability within a day, is obtained by linear curve-fitting, which yields added parameters: a midline-estimating statistic of rhythm, the MESOR (a time structure or chronome-adjusted mean), the circadian acrophase, a measure of timing of overall high values recurring in each cycle, and the amplitudes and acrophases of the 12-hour (and higher order) harmonic(s) of the circadian variation that, with the characteristics of the fundamental 24-hour component, describe the circadian waveform. The MESOR is a more precise and more accurate estimate of location than the arithmetic mean. The major risks associated with CHAT and/or DHRV have been documented by measurements of blood pressure and heart rate at 1-hour or shorter intervals for 48 hours on populations of several hundred people, but these risks are to be assessed in a 7-day/24-hour record in individuals before a physical examination, for the following reasons. (1) The average derived from an around-the-clock series of blood pressure measurements, computed as its MESOR, the proven etiopathogenetic factor of catastrophic vascular disease, can be above chronobiologic as well as World Health Organization limits for 5 days or longer and can be satisfactory for months thereafter, as validated by continued automatic monitoring. The MESOR can be interpreted in light of clock-hour-, gender-, and age-specified reference limits and thus can be more reliably estimated with a systematic account of major sources of variability than by casual time-unspecified spot checks (that conventionally are interpreted by a fixed and, thus, rhythm, gender-, and age-ignoring limit). With spot checks, in a diagnostically critical range of "borderline" blood pressures, an inference can depend on the clock-hour of the measurement, usually providing a diagnosis of normotension in the morning and of hypertension in the afternoon (for the same diurnally active, nocturnally resting patient!). Long-term treatment must not be based upon the possibility of an afternoon vs a morning appointment. Moreover, the conventional approach will necessarily miss cases of CHAT that are not accompanied by MESOR hypertension. (2) Circadian hyper-amplitude-tension indicates a greater risk for stroke than does an increase in the around-the-clock average blood pressure (above 130/80 mm Hg) or old age, whereas (3) CHAT can be asymptomatic, as can MESOR hyptertension. (4) Deficient heart rate variability, the fall below a threshold of the circadian standard deviation of heart rate, an entity in its own right, is also a chronome alteration of heart rate variability (CAHRV). Deficient heart rate variability can be present together with CHAT, doubling the relative risk of morbid events. In each case--either combined with CHAT or as an isolated CAHRV--a DHRV constitutes an independent diagnostic assessment provided as a dividend by current blood pressure monitors that should be kept in future instrumentation designs. CHAT and DHRV can be screened by systematic focus on variability, preferably by the use of automatic instrumentation and analyses, which are both available (affordably) for research in actual practice, in conjunction with the Halberg Chronobiology Center at the University of Minnesota.
Young (20-30-year-old) and older (60-76-year-old) adults were tested on two measures of rhythmic performance. The first involved tapping at the subject's own preferred rate, a measure of so-called internal tempo. Over five sessions of testing, tapping rates were consistently and significantly slower on average in the older subjects than the younger ones, but rates were not relatively more variable in older subjects (i.e., coefficients of variation, standard deviation/mean, did not differ between the older and young people). In addition, both old and younger subjects performed on a synchronized-tapping and continuation task of the type used by Wing and Kristofferson (1973, Perception and Psychophysics, 14, 3-12). Target interresponse times were 300, 400, 500, 600, and 700 ms, and in all cases interresponse intervals produced by both the old and young adults matched the target times very closely. Wing and Kristofferson's analytical procedure was used to decompose tapping variance into that attributable to timing processes and that resulting from motor implementation of the timing signal. Both sorts of variance increased with increasing target interresponse time (with timer variance increasing most markedly), but no difference was found in either type of variance in comparisons between the old and younger subjects. If the internal tempo measure directly reflects the speed of internal timing processes, the data suggest that such processes are slower, but not relatively more variable, in older than younger subjects (consistent with some previous evidence and speculation), but that the calibration of performance forced by the synchronization task will make such an age-related difference in "internal clock speed" unobservable on synchronized-tapping tasks.
We examined the effects of age and time of day on balance performance in the gray mouse lemur (Microcebus murinus) in relation to body temperature variations. Groups of young, adult and aged animals were entrained to either short (SP, L/D 10/14) or long photoperiod (LP, L/D 14/10) and tested in the accelerating Rotarod at three phases of their light/dark cycle (beginning and end of the light phase, beginning of the dark phase). In addition, for each test, rectal temperature (Tr) was measured. Under LP, whatever the test phase, this primate showed a clear age-related decrease in balance performance. Under SP, no significant age-related decline in balance could be detected. Whatever the photoperiod, an effect of time of day on balance performance could only be seen in adults, with better performances at the beginning of the dark phase when Tr values were higher. Under LP, daily variations of both balance performance and Tr disappeared with advancing age. Consequently, age differences were substantially greater when testing was conducted during the dark phase of the light/dark cycle. The time of day effect on balance performance and the loss of daily variations with age suggest the influence of age-related changes within the biological clock.
OBJECTIVE: To investigate the relationship between drainage angle configuration with untreated intraocular pressure (IOP) and optic disc cupping in subjects with chronic angle-closure glaucoma (CACG). DESIGN: Prospective, observational study. PARTICIPANTS: Two hundred seventy-five Asian subjects with CACG who participated in a randomized controlled trial that investigated the IOP-reducing effect of latanoprost and timolol. METHODS: Chronic angle-closure glaucoma was defined as the presence of glaucomatous optic neuropathy (with or without a visual field defect), an anterior chamber angle in which the pigmented trabecular meshwork was not visible for at least 180 degrees on gonioscopy, and evidence of peripheral anterior synechiae (PAS) in association with elevated IOP of 21 mmHg or more. Static and dynamic gonioscopy were performed, the angles were graded in each quadrant according to the Shaffer scheme, and the number of clock hours of PAS was recorded. The untreated IOP and vertical cup-to-disc ratio were correlated with mean angle width and extent of PAS. MAIN OUTCOME MEASURES: Mean angle width, clock hours of PAS, IOP, and vertical cup-to-disc ratio. RESULTS: Most subjects were female (75%), and the mean age was 62.9+/-9.4 years. The mean angle width was 0.77+/-0.53 and the mean number of clock hours of PAS was 4.77+/-3.2 hours. Untreated IOP correlated with angle width (r = -0.23; P<0.001) and clock hours of PAS (r = 0.22; P<0.001). Vertical cup-to-disc ratio also correlated with angle width (r = -0.17; P = 0.004) and PAS (r = 0.28; P<0.001). Performing a multiple linear regression using baseline IOP as the outcome variable with age, gender, clock hours of PAS, and angle width as predictors, there was a 0.39-mmHg (95% confidence interval, 0.15-0.63) increase in baseline untreated IOP for each unit increase in clock hours of PAS (P = 0.002). CONCLUSIONS: In subjects with CACG, the extent of PAS and a narrower width of the drainage angle were associated with higher untreated IOP and a larger vertical cup-to-disc ratio.
The human genome harbors many distinct families of human endogenous retroviruses (HERVs) that stem from exogenous retroviruses that infected the germ line millions of years ago. Many HERV families remain to be investigated. We report in the present study the detailed characterization of the HERV-K14I and HERV-K14CI families as they are represented in the human genome. Most of the 68 HERV-K14I and 23 HERV-K14CI proviruses are severely mutated, frequently displaying uniform deletions of retroviral genes and long terminal repeats (LTRs). Both HERV families entered the germ line approximately 39 million years ago, as evidenced by homologous sequences in hominoids and Old World primates and calculation of evolutionary ages based on a molecular clock. Proviruses of both families were formed during a brief period. A majority of HERV-K14CI proviruses on the Y chromosome mimic a higher evolutionary age, showing that LTR-LTR divergence data can indicate false ages. Fully translatable consensus sequences encoding major retroviral proteins were generated. Most HERV-K14I loci lack an env gene and are structurally reminiscent of LTR retrotransposons. A minority of HERV-K14I variants display an env gene. HERV-K14I proviruses are associated with three distinct LTR families, while HERV-K14CI is associated with a single LTR family. Hybrid proviruses consisting of HERV-K14I and HERV-W sequences that appear to have produced provirus progeny in the genome were detected. Several HERV-K14I proviruses harbor TRPC6 mRNA portions, exemplifying mobilization of cellular transcripts by HERVs. Our analysis contributes essential information on two more HERV families and on the biology of HERV sequences in general.
The objective of this paper is to evaluate age and associated factors affecting anorectal pressure profilometry in anal-continent women with lower urinary tract symptoms. One hundred and ten anal-continent women (mean age, 47.7+/-12.8 years; range, 23-87 years) with lower urinary tract symptoms voluntarily participated in this study after undergoing a complete urogynecological evaluation including a multichannel urodynamic study. Anorectal pressure was evaluated by using a radial four-channel manometry with a water-filled catheter, which was placed 10 cm into the anorectum above the anal verge. We divided the anorectal pressure profile into five segments and four axes to clarify the axis-specific defect or site-specific damage in the sphincter profile. The aging process had a negative effect on the peak resting pressure from the 41 to 100th percentile of the anorectal pressure profile at 12 o'clock, 3 o'clock, and 6 o'clock (P<0.05). With voluntary squeezing, aging had negative effects on the peak squeeze pressure from the 41 to 100th percentile of the anorectal pressure profile at 3 o'clock, and 61 to 80 percentile at 12 o'clock (P<0.05). There is a trend where anorectal pressure reduces as a woman ages, especially at the anal sphincter area in women with lower urinary tract symptoms. The anterior and left sides of the anorectal sphincter seem to be the most vulnerable in the aging process.