Can Aging Develop as an Adaptation to Optimize Natural Selection? (Application of Computer Modeling for Searching Conditions When the "Fable of Hares" Can Explain the Evolution of Aging).

There are two points of view on the evolution of aging. The classical theory of aging suggests that natural selection does not efficiently eliminate mutations or alleles that are harmful to organisms at later age. Another hypothesis is that the genetic program of aging has evolved as an adaptation that contributes to the optimization of the evolutionary process. Academician V. P. Skulachev advocates the latter hypothesis, which he has illustrated with the "Fable of hares". In this paper, we have used computer simulation to search for conditions when, according to the "Fable", aging develops as an adaptation required for the evolution of useful traits. The simulation has shown that the evolutionary mechanism presented in the "Fable of hares" is only partially functional. We have found that under certain conditions, programmed deterioration of some organismal functions makes it possible to increase the efficiency of natural selection of other functions. However, we have not identified mechanisms that would ensure the distribution and support of genes of aging within the population.

Choosing between bad, worse and worst: what is the preferred mode of delivery for failure of the second stage of labor?

OBJECTIVE: To determine the preferred mode of delivery (vacuum, forceps or cesarean delivery) for second-stage dystocia. METHODS: Retrospective cohort study of women delivered by forceps, vacuum or cesarean delivery due to abnormalities of the second stage of labor. Primary outcome included neonatal and maternal composite adverse effects. RESULTS: A total of 547 women were included: 150 (27.4%) had forceps delivery, 200 (36.5%) had vacuum extraction, and 197 (36.1%) had cesarean section. The rate of neonatal composite outcome was significantly increased in vacuum extraction (27%) compared to forceps delivery (14.7%) or cesarean section (9.7%) (p < 0.001). There was no difference in the rate of maternal composite outcome among the groups. Both operative vaginal delivery modes were associated with significantly lower rate of postpartum infection compared to cesarean delivery (0% versus 3%, p = 0.004). CONCLUSION: Operative vaginal delivery was associated with reduced postpartum infection compared to cesarean section. Forceps delivery was associated with reduced risk for adverse neonatal outcome compared to vacuum extraction, with no increase in the risk of composite maternal complications.

Postharvest changes in water status and chlorophyll content of lettuce (Lactuca sativa L.) and their relationship with overall visual quality.

The purpose of this study was to evaluate water status, chlorophyll content (C), and overall visual quality (OVQ) of fresh butter lettuce (Lactuca sativa var. Lores) as well as these indexes' evolution during storage and their relationships, if any. Whole lettuce plants were stored at optimal postharvest conditions (0 to 2 degrees C and 97% to 99% relative humidity). Measured parameters during each sampling day were relative water content (RWC), water content (WC), free water (FW), bound water (BW), free water to total water ratio (FW/TW), C, and OVQ. All parameters were evaluated in the external, middle, and internal zones of lettuce heads. The external zone had higher initial values of RWC, WC, and FW than the internal zone. The external zone yielded the highest FW/TW ratio (85%), indicating that external leaves had more water available to be used in degradation reactions and were more perishable, with the lowest shelf life if compared with the other lettuce zones. During storage, water status index evolution differed from zone to zone. An increase in BW and a decrease in FW were detected in all lettuce zones. RWC turned out to be a more sensitive measurement than WC. Yet RWC showed no significant correlation with any index. The OVQ parameter correlates with FW directly, or indirectly through FW/TW in all lettuce zones; therefore, FW is an objective and quantitative measurement, which impacts on the visual quality of butter lettuce. The decrease in chlorophyll content observed in the external leaves strongly correlated with the decrease in OVQ.

Patterns of carpal development among anuran amphibians.

The unity and diversity of developmental processes in the vertebrate limb have singular importance in the interpretation of evolutionary hypotheses of tetrapod diversification. In anurans, the intraordinal diversity of forelimbs seems to be related to the fusion of distal carpals, whereas proximal carpals are invariable. However, there are different ontogenetic pathways involved in the differentiation of proximal carpals. This study presents a comparative analysis of early developmental features in one archeobatrachian and 23 neobatrachian species representing five families and explores the variability in the differentiation of carpal cartilages. We found new evidence supporting the presence of an embryonic intermedium that incorporates with the ulnare. Difference between the pipid Xenopus and the neobatrachians is interpreted as a change in the rate of differentiation of Distal Carpal 5 that does not affect the developmental pattern of digits. The developmental variability exhibited by the intermedium, radiale, and Element Y is combined in patterns that converge on the same adult carpal morphology among neobatrachians; these patterns appear to contain potentially useful phylogenetic information.

Activin A and follistatin are dynamically regulated during human pregnancy.

Activin A (beta A-beta A) and activin B (beta B-beta B) are related dimeric proteins that regulate numerous cellular activities. Activin activity is bioneutralized by follistatin, a specific and high-affinity binding protein. Recently, our group developed specific and sensitive enzyme-linked immunosorbent activin assays that do not detect either activin isoform when bound to follistatin, therefore, the assays are specific for biologically relevant ligands. Activin A is measurable in the serum of pregnant women (cross-sectional sample collection), while activin B is not detected in maternal serum. However, activin B is measurable in amniotic fluid and cord blood sera. The purpose of this study was to measure serum activin A, activin B, and follistatin prospectively in longitudinally collected samples during pregnancy. This study design offered observations of relative changes in serum hormone concentration with each person serving as an internal reference. Serum samples were collected bimonthly from seven pregnant women beginning within the second month of gestation, and up to, but not including, the onset of labor. Six of the seven women had normal labor and delivery. One patient required pitocin (an oxytocin agonist) for induction of labor which led to delivery. Activin A, activin B, total follistatin, free follistatin, human chorionic gonadotropin, estradiol, progesterone, FSH, and LH were measured in maternal serum samples using specific assays. Serum activin A levels increased in the final month of pregnancy in the six patients who delivered following normal labor (< 0.78 ng/ml (first trimester) to 1-6 ng/ml (term)). Activin B was not detected in any serum sample (< 0.78 pg/ml). Total serum follistatin (free follistatin, follistatin-activin, and follistatin-inhibin) increased 10- to 45-fold in the final month of pregnancy in four of the women undergoing normal labor (10 ng/ml (first trimester) to 100-450 ng/ml (final month)). Total follistatin was high and variable in two women throughout pregnancy. Total follistatin returned to basal serum concentration in three of the patients during the last 2 weeks of pregnancy. Free follistatin was detected throughout pregnancy (range < 2-35 ng/ml). Free follistatin represented a small percentage of the total follistatin throughout the time of pregnancy and did not rise coincident with the rise in total follistatin. Serum activin A and activin B were not detected during the entire course of pregnancy in the one patient who did not have normal labor and total follistatin did not rise in the last trimester of pregnancy. Gonadotropin and steroid hormones were measured in all patients and were within normative ranges for human pregnancy (inclusive of the non-laboring patient). The results suggest that immunodetectable activin A is present in the third trimester of pregnant women who have normal onset labor. The total follistatin assay results suggest that follistatin-activin (or -inhibin) complexes are upregulated during the third trimester of pregnancy. Importantly, activin A production exceeds the binding capacity of circulating follistatin. Because binding protein free activin A is biologically active we conclude that the activin A detected in late pregnancy is biologically relevant. The findings are consistent with our hypothesis that activin A is an endocrine factor during the last trimester of human pregnancy and may be involved in normal labor.

Pregnancy rates after operative endoscopic treatment of total (neosalpingostomy) or near total (salpingostomy) distal tubal occlusion.

OBJECTIVE: To determine the efficacy of the endoscopic treatment of complete distal tubal occlusion or moderate to severe tubal phimosis and to analyze outcome using contemporary statistical methodologies. DESIGN: Prospective cohort analysis. SETTING: Tertiary-care institution. PATIENTS: One hundred thirteen consecutive patients undergoing a neosalpingostomy or salpingostomy. INTERVENTIONS: KTP/532 laser (Laserscope, Santa Clara, CA) laparoscopy. Additional infertility factors were treated postoperatively. MAIN OUTCOME MEASURES: Crude pregnancy rate (PR), monthly fecundity rate, monthly probability of pregnancy, cure rate, and cumulative PRs. Outcome was compared on the basis of the surgical procedure performed. The impact of endometriosis as well as other fertility factors was analyzed. RESULTS: Twenty-three patients conceived yielding a crude PR of 20.4%, a monthly fecundity rate of 2.6%, a monthly probability of pregnancy of 6.4%, and a cure rate of 52.4%. There were six ectopic pregnancies (5.3%). A significant difference was found among the cumulative pregnancy curves. The cumulative pregnancy curve for unilateral salpingostomy differed significantly from that of unilateral neosalpingostomy. Patients with endometriosis and no other infertility factors had a significantly better cumulative pregnancy curve compared with patients without endometriosis or other factors as well as compared with patients with no endometriosis but with other infertility factors. Patients undergoing bilateral neosalpingostomy had a cure rate of 9.0% whereas patients undergoing bilateral salpingostomy had a cure rate of 34.2%. CONCLUSIONS: Operative endoscopy yields PRs that are comparable to those reported in the literature for laparotomy. The presence of complete bilateral distal tubal occlusion has a negative impact on outcome.

Inhibin suppresses human chorionic gonadotropin secretion in term, but not first trimester, placenta.

Inhibin is produced by the placenta, with serum concentrations rising throughout pregnancy. In contrast, hCG serum concentrations peak in the first trimester and are 80-90% lower at term. This study was designed to determine the effect of inhibin on hCG secretion both early and late in gestation. Villus tissue from 3 term and 3 first trimester (8-10 week) placentas was maintained in an in vitro explant culture model for 5 days. Tissue from each placenta was incubated with control medium in 24 replicate wells for the first 72 h. During the final 48 h, 12 wells received control medium, and 12 wells received medium containing 1% rabbit antiserum raised against the alpha-subunit (residues 1-32) of the human inhibin peptide. The antiserum demonstrated biological activity by increasing serum FSH concentrations in an immature female rat bioassay. The relative increase in hCG secretion at the conclusion of days 4 and 5 in control and antiserum-treated groups for each first trimester and term placenta were compared to pretreatment hCG concentrations on day 3. The relative increases in hCG secretion of first trimester control groups on day 4 (mean +/- SD, 34 +/- 11%) and day 5 (63 +/- 23%) were compared to those in antiserum-treated groups on day 4 (39 +/- 13%) and day 5 (54 +/- 5%) and showed no significant difference between groups on either day. The same comparison in term cultures showed the relative increases in hCG secretion of control groups on day 4 (31 +/- 10%) and day 5 (64 +/- 50%) to be significantly lower than those in antiserum-treated groups on day 4 (100 +/- 41%) and day 5 (150 +/- 108%; P less than 0.001). These findings suggest that inhibin suppresses hCG secretion in term, but not first trimester, placentas.

Substance misuse training in nursing, psychiatry, and social work.

This is a survey study of American schools of nursing, psychiatry residency programs, and schools of social work to develop information on the extent to which nurses, psychiatrists, and social workers are prepared in their professional education to identify and treat substance misusers. Results describing nature, format, and extent of training experiences are presented for didactic and patient contact components of programs. Results are discussed in light of the finding that not much time is devoted to substance misuse in the professional preparation of these health care providers.

A study of underreporting of Down's syndrome on birth certificates in an Ohio County, 1970-78.

In a previous statewide assessment in Ohio of the percentage reporting of Down's syndrome (DS) on birth certificates, it was found that 33.9 percent of the cases chromosomally analyzed were so recorded. The objectives of this study were to gain a greater understanding of the basis of this low reporting percentage by concentrating on Hamilton County births only, to compare these percentages among hospitals in the county, and to determine the commonality of their causes. Since it was anticipated that both a thorough search of hospital records and access to chromosome analysis records would provide essentially complete ascertainment of DS births in the county during 1970-78, the data were also used to test the validity of chromosome analysis as a sampling procedure in estimating the total number of DS births by means of the Lincoln-Peterson capturerecapture method.The percentage of reporting of DS on the birth certificates by hospital ranged from 0.0 to 57.1, with a mean of 26.0 for the 6 hospitals within the county. Although variation among some hospitals was statistically significant, three of the six hospitals had zero percent reporting. The explanation for these low reporting percentages was fundamentally similar for all hospitals-a communications flow problem, produced by poor timing and use of the wrong sources of available information. The only data typically available to the birth certificate clerk were derived from the labor and delivery sheet, the form with the worst reporting percentage of DS of any in the medical record. On the other hand, by the time of discharge, 92.5 percent of the cases had either been definitely diagnosed as DS and were recorded on the face sheet or were entered as "chromosome analysis pending" in the file.The use of the chromosome analysis data gave an estimate of total DS births (N = 201 +/- 34) statistically consistent with the total observed, thereby providing support for this estimation procedure. Annual incidence rates for DS were also calculated for 1970-78, with a total incidence rate for the 9-year period of 1.14 per 1,000 live births.

Down's syndrome: percentage reporting on birth certificates and single year maternal age risk rates for Ohio 1970-79: comparison with upstate New York data.

Estimates of single year maternal age risk rates for Down's Syndrome births to White residents of Ohio over the period 1970-79 are reported. The rates were estimated from birth certificate data, which first necessitated estimating the percentage of reporting of Down's Syndrome on Ohio birth certificates. Using data from cytogenetic laboratories within the state, percentages of Down's Syndrome cases reported were found to be 36.5 (319/875) for White and 33.9 (342/1,010) overall. Final single year maternal age risk rates reported here are corrected for underreporting using these figures. They should be useful for genetic counselors and obstetricians. Comparisons of observed, uncorrected single year maternal incidence rates were made within Ohio 1970-74 vs 1975-79, and between Ohio and upstate New York for various time periods using both a hierarchial log-linear model for multiway cross-tabulations and a weighted least squares solution. All comparisons showed excellent agreement, indicating no evidence for temporal or geographic differences and implying that environmental factors are unimportant in determining single year maternal age incidence rates in Down's Syndrome for the time periods and populations studied.

Haemopoietic stem cells in the foetal mouse thymus.

The presence of haemopoietic stem cells (HSC) in the foetal mouse thymus was assessed to determine whether all cells which enter the developing organ are precommitted to thymocyte differentiation, or if stem cell multipotentiality still exists. The Till and McCulloch spleen colony assay was used to delineate foetal-thymus derived HSC in lethally irradiated recipients. Of the range examined, between 13 days of gestation to birth, a peak of stem cell activity occurs in 15-day foetal thymus. The surface colonies produced by the thymus-derived HSC are small compared to colonies produced by the liver derived HSC, although well within the range of the latter. Histologically, five types of colonies were identifiable which were produced by the thymus-derived HSC, indicating that these cells retain the potential to form a wide range of differentiated colonies.

Maternal alloimmunisation in pregnancy. In vitro studies of T cell-dependent immunity to paternal alloantigens.

A secondary in vitro allograft reaction was used to demonstrate that spleen cells derived from allogeneically mated inbred mice were immunised against paternal alloantigens. In addition to the heightened alloantigen-specific in vitro response of these spleen cells, it was also found that spleen cells froma a wide variety of syngeneically and allogeneically mated mice were nonspecifically more reactive in the in vitro allograft reaction than spleen cells from virgin mice. However, when spleen cells freshly harvested from allogeneically mated mice were tested in a direct 51Cr release assay, lysis of target cells bearing the paternal alloantigens was demonstrable in only one-third of the experiments. It is proposed that T cell immunisation to paternal alloantigens occurs in pregnancy, but that cell-mediated cytotoxicity is inhibited.

Development of the rabbit appendix. I. Electron-microscopic observations.

The progressive lymphoepithelial development of the rabbit appendix was examined by light and electron microscopy. At 5 days postnatally, the appendix wall primitively resembles the mature organ but lacks both the discrete lymphoid organization and most cell types. The dome appears to be the first recipient of lymphoid cells. By 18 days the lymphoid nodule has become compartmentalized and lymphoid. The epithelium, although not fully developed, is in contact with the lymphocytes of the dome. The 5-week-old appendix has all the lymphoepithelial components of the adult but lacks the size of the mature organ. At all ages reported, plasma cells and dendritic cells are absent. Bacteria, thought to be essential to appendical lymphoid development, are not apparent at 5 or 18 days. The features common to central or peripheral lymphoid tissues are discussed.