The Rb1 tumour suppressor gene modifies telomeric chromatin architecture by regulating TERRA expression.

The tumour suppressor gene (Rb1) is necessary for the maintenance of telomere integrity in osteoblastic cells. We now show that the compaction of telomeric chromatin and the appropriate histone modifications of telomeric DNA are both dependent upon Rb1-mediated transcription of the telomere-derived long non-coding RNA TERRA. Expression of TERRA was reduced in Rb1 haploinsufficient cells, and further decreased by shRNA-mediated reduction of residual Rb1 expression. Restoration of Rb1 levels through lentiviral transduction was sufficient to reestablish both transcription of TERRA and condensation of telomeric chromatin. The human chromosome 15q TERRA promoter contains predicted retinoblastoma control elements, and was able to confer Rb1-dependent transcription upon a promoterless reporter gene. Chromatin immunoprecipitation revealed preferential binding of phosphorylated over non-phosphorylated Rb1 at the TERRA promoter. As Rb1-deficient cells show increased genomic instability we suggest that this novel non-canonical action of Rb1 may contribute to the tumour suppressive actions of Rb1.

Detection of swing heel-off event in gait initiation using force-plate data.

This study investigated the accuracy and reliability of four methods using force-plate data for detecting the swing heel-off (HO) time in gait initiation. Results of these methods were compared to those obtained by means of a reference method using a footswitch. Ten young healthy adults performed 18 forward gait initiation trials at self-selected speed and at maximal speed. Results showed that the method based on vertical impulse was the most accurate and reliable in determining HO in both speed conditions. The mean error obtained with this method was -8±10ms in the self-selected speed condition (-7±10ms in the maximal speed condition), with no significant effect of gait speed (P>0.05). These findings suggest that this method based on force-plate data is valid and reliable for detecting HO in forward gait initiation in the absence of additional hardware.

The influence of variable resistance moment arm on knee extensor performance.

To enhance muscular strength, resistance training machines with a cam, incorporating a variable resistance moment arm, are widely used. However, little information is available about the influence of the variable resistance moment arm on torque, velocity, and power during muscle contraction. To address this, a knee extensor machine was equipped with a cam or with a semi-circular pulley that imposed a variable or a constant resistance moment arm, respectively. Fourteen physically active men performed two full knee extensions against loads of 40-80 kg in both conditions. Participants developed significantly higher torque with the pulley than with the cam (P < 0.001). The relative differences between pulley and cam conditions across all loads ranged from 8.72% to 19.87% (P < 0.001). Average knee extension velocity was significantly higher in the cam condition than in the pulley condition. No differences were observed in average and peak power, except at 50 and 55 kg. Torque-velocity and power-velocity relationships were modified when the resistance moment arm was changed. In conclusion, whatever the link, namely cam or pulley, the participants produced similar power at each load. However, the torque-velocity and power-velocity relationships were different in the cam and pulley conditions. The results further suggest that the influence of the machine's mechanism on muscular performance has to be known when prescribing resistance exercises.

Performance of Doppler ultrasonography as a screening test in low risk pregnancies: results of a multicentric study.

To assess the efficacy of the Doppler velocimetry of the uterine and umbilical arteries as a screening test for preeclampsia and fetal growth retardation, we studied 916 low risk pregnancies. The S/D ratios of the uterine and umbilical arteries were obtained at 19 to 24 weeks and at 26 to 31 weeks of gestational age. Mean values, receiver operator curves, and the diagnostic accuracy of the tests were calculated for the following end-points: (1) pregnancy-induced hypertension, (2) low birth weight for gestational age, (3) small for gestational age with abnormal outcome, (4) pregnancy-induced hypertension needing preterm delivery. The prevalences for these outcomes were 3.4%, 4.6%, 1%, and 0.7%, respectively. The study was blinded. The umbilical and uterine artery S/D ratios were significantly higher in the abnormal than in the normal outcome group. When uterine arteries were studied at 19 to 24 weeks, sensitivity was 59% in the detection of pregnancy-induced hypertension, 11% in the detection of small for gestational age fetuses, 33% in the detection of small for gestational age fetuses with abnormal outcome, and 83% in the detection of pregnancy induced hypertension needing preterm delivery; the corresponding values for specificity were 69%, 94%, 94%, and 68%. At 26 to 31 weeks the sensitivity values were respectively, 69%, 58%, 75%, and 100% and specificity values were 80%, 59%, 39%, and 79%. When umbilical arteries were studied at 19 to 24 weeks, sensitivity was 38% in the detection of pregnancy-induced hypertension, 46% in the detection of small for gestational age fetuses, 78% in the detection of small for gestational age fetuses with abnormal outcome, and 67% in the detection of pregnancy-induced hypertension needing preterm delivery. The corresponding values of specificity were 74% for all four groups. At 26 to 31 weeks the sensitivity values were 38%, 43%, 87%, and 67%, respectively, and specificity values were 80% for all four groups. We concluded that Doppler examinations of the uterine and umbilical arteries can detect, at midpregnancy, the severe forms of pregnancy-induced hypertension and small for gestational age fetuses but they cannot be used to screen a low risk population in which the prevalence of the disease is low, and hence the positive predictive value is low.

Can ultrasound be used to screen uterine malformations?

Eighty-nine patients were examined by ultrasound during the second phase of the menstrual cycle. The operators were not aware of the patients' history or results of previous ultrasonographic or radiologic investigations. The operators' aim was to diagnose uterine malformations graded as normal, suspected, or abnormal. Ultrasound identified 7 of 9 patients with a didelphic or complete septate uterus and 2 out of 3 with a bicornuate or partial septate uterus. Two other cases were suspected (one with a unicornuate, the other with a didelphic uterus). One false-positive case occurred, and 10 patients were not identified as having a malformed uterus (sensitivity, 42.9%; specificity, 97.8%). False-negatives involved mainly minor malformations.

Characteristics of women under 20 with cervical intraepithelial neoplasia.

The relationship between risk of cervical neoplasia and various sociodemographic, reproductive and sexual characteristics was studied in 126 women (cases) with an abnormal Papanicolaou test finding and 1914 controls seen at the same clinic in which cases were detected but showing no evidence of cervical neoplasia. All the subjects of this study were under the age of 20. Number of sexual partners and clinical occurrence of genital warts emerged as the most important determinants of the risk of cervical intraepithelial neoplasia (CIN) in these very young women (Relative Risk (RR) for three or more sexual partners = 2.45, 95% Confidence Interval (CI) 1.63-3.70, RR for occurrence of genital warts, adjusted for number of sexual partners = 9.15, 95% CI: 5.06-16.26). Also having grown up in a 'problem' family seemed to increase the probability of developing CIN (RR adjusted for number of partners = 1.64, 95% CI 1.06-2.52). For all other investigated characteristics, cases and controls were remarkably similar. These include socioeconomic status, parity, smoking habits, use of various contraceptive methods and also indicators of sexual activity such as age of first having sexual intercourse, and duration and frequency of intercourse. Although this group of women under 20 only allows the study of less severe precursors of cervical cancer, it helps to highlight the earliest effect of purported risk factors for cervical neoplasia, chiefly sexual habits, at a time very close to their being established.

[Socio-sanitary analysis of the first 300 voluntary interruptions of pregnancy carried out in the obstetrical-gynecological division of the Bassini Hospital of Milan]. / Analisi socio-sanitaria sulle prime 300 interruzioni volontarie di gravidanza effettuate dalla Divisione Ostetrico-Ginecologica dell'Ospedale Bassini di Milano.

PIP: 300 abortion seekers were interviewed to investigate the causes leading to interruption of pregnancy, and the characteristics of the women themselves. 19% were below 20, and 10% below 18 years of age; 26% were immigrants from the south of Italy, and most had a very low educational and socioeconomic status. About 30% were housewives, and 57% were married. 90% of partners were favorable to the intervention, while the great majority of parents did not know about it. Socioeconomic reasons were given more often for the request of abortion. 67.7% of interventions were performed after the 8th week of pregnancy; 93% of women declared they would have seeked abortion any way, even if it had not been legal. The most used contraceptive method at the time of conception was coitus interruptus; the pill or the IUD were used by only 1.5% of women, while 25% did not use any form of contraception.^ieng