Phenotypic diversity in siblings with partial androgen insensitivity syndrome

The androgen insensitivity syndrome is a heterogeneous disorder with a wide spectrum of phenotypic abnormalities, ranging from complete female to ambiguous forms that more closely resemble males. The primary abnormality is a defective androgen receptor protein due to a mutation of the androgen receptor gene. This prevents normal androgen action and thus leads to impaired virilisation. A point mutation of the androgen receptor gene affecting two siblings with partial androgen insensitivity syndrome is described. One had cliteromegaly and labial fusion and was raised as a girl, whereas the other sibling had micropenis and penoscrotal hypospadias and was raised as a boy. Both were shown to have the arginine 840 to cysteine mutation. The phenotypic variation in this family is thus dependent on factors other than abnormalities of the androgen receptor gene alone.     

Actuarial survival in the premature infant less than 30 weeks' gestation

OBJECTIVE: Because survival from admission to discharge does not provide parents and physicians information about future life expectancy in the premature neonate, we characterized the actuarial survival, defined as the future life expectancy from a given postnatal age, in a large inborn population of premature infants < 30 weeks' gestation. STUDY DESIGN: We determined daily actuarial survival of 1925 inborn infants (23 to 29 weeks' gestation) admitted to the Baylor Affiliated Nurseries from July 1986 through December 1994, stratified by 100-g birth weight and by 1-week gestational-age intervals. RESULTS: In the 501- to 600-g birth weight stratum, actuarial survival improved from 31% at birth, to 61% on day of life 7, and then to 75% on day of life 28; in the 901- to 1000-g birth weight stratum, actuarial survival improved from 88%, to 94%, and then to 98% throughout the same times, respectively. Similar trends were obtained when data were stratified by gestational age. CONCLUSIONS: Survival in the smallest infants improves dramatically during the first few days of life, but there is a significant risk for late death in the smallest of these infants.     

Antisense RNA-mediated reduction of p53 induces malignant phenotype in nontumorigenic rat urothelial cells

p53 mutation is commonly associated with high-grade, high-stage human urothelial carcinomas. Recent studies suggest that p53 mutation in low- grade, low-stage bladder carcinomas may be correlated with the progression of the disease. In the present study, we used antisense RNA methodology in vitro to evaluate the significance of the loss of p53 function at an early stage of urinary bladder carcinogenesis. An immortalized nontumorigenic rat urothelial cell line (MYP3) that strongly expresses wild-type (WT) p53 was transfected with a plasmid (pcDL-SR alpha-296) containing a rat WT p53 cDNA in antisense orientation. The transfection resulted in a significant reduction in p53 mRNA expression and protein synthesis, in stimulation of anchorage- dependent growth, and in acquisition of anchorage-independent growth potential. Three such clones, when tested in athymic nude mice, all formed muscle-invasive, high-grade transitional cell carcinomas at s.c. injection sites. When cells were inoculated into an orthotopic site (urinary bladder), one of two antisense transfectants tested formed bulky tumors in the bladder in all seven nude mice and metastases to lungs in three of the seven mice. Analysis of these cells revealed a decrease in the expression of p21 (WAF1, sdi1, or CIP1) and retinoblastoma (Rb) gene product. Phosphorylation of Rb protein was not inhibited when the cells were starved. No significant difference was observed in the expression of p16 protein. In cell cycle analysis, all antisense transfectants tested escaped from G1 arrest by starvation. Furthermore, secretion of interleukin (IL)-6 into culture medium was increased significantly. Treatment with anti-IL-6 antibody suppressed anchorage-dependent growth. This study directly demonstrates that the loss of p53 function at an early stage of urothelial carcinogenesis may result in acquisition of a malignant phenotype by regulating IL-6 production as well as cell cycle related genes.      

Behavioural insights and the evolving COVID-19 pandemic

Behavioural sciences have complemented medical and epidemiological sciences in the response to the SARS-CoV-2 pandemic. As vaccination uptake continues to increase across the EU/EEA – including booster vaccinations – behavioural science research remains important for both pandemic policy, planning of services and communication. From a behavioural perspective, the following three areas are key as the pandemic progresses: (i) attaining and maintaining high levels of vaccination including booster doses across all groups in society, including socially vulnerable populations, (ii) informing sustainable pandemic policies and ensuring adherence to basic prevention measures to protect the most vulnerable population, and (iii) facilitating population preparedness and willingness to support and adhere to the reimposition of restrictions locally or regionally whenever outbreaks may occur. Based on mixed-methods research, expert consultations, and engagement with communities, behavioural data and interventions can thus be important to prevent and effectively respond to local or regional outbreaks, and to minimise socioeconomic and health disparities. In this Perspective, we briefly outline these topics from a European viewpoint, while recognising the importance of considering the specific context in individual countries.     

Amlodipine reduces blood pressure during dynamic resistance exercise in hypertensive patients

This study investigated the effect of the dihydropyridine calcium channel antagonist, amlodipine, on blood pressure (BP) during resistance exercise performed at different intensities in hypertensives. Eleven hypertensives underwent 4 weeks of placebo and amlodipine (random double‐blinded crossover design). In each phase, they performed knee extension exercise until exhaustion following three protocols: one set at 100% of 1 RM (repetition maximum), three sets at 80% of 1 RM, and three sets at 40% of 1 RM. Intraarterial BP was measured before and during exercise. Amlodipine reduced maximal systolic/diastolic BP values achieved at all intensities (100% = 225 ± 6/141 ± 3 vs. 207 ± 6/130 ± 6 mmHg; 80% = 289 ± 8/178 ± 5 vs. 273 ± 10/169 ± 6 mmHg; 40% = 289 ± 10/176 ± 8 vs. 271 ± 11/154 ± 6 mmHg). Amlodipine blunted the increase in diastolic BP that occurred during the second and third sets of exercise at 40% of 1RM (+75 ± 6 vs. +61 ± 5 mmHg and +78 ± 7 vs. +64 ± 5 mmHg, respectively). Amlodipine was effective in reducing the absolute values of systolic and diastolic BP during resistance exercise and in preventing the progressive increase in diastolic BP that occurs over sets of low‐intensity exercise. These results suggest that systemic vascular resistance is involved in BP increase during resistance exercise, and imply that hypertensives receiving amlodipine are at lower risk of increased BP during resistance exercise than non‐medicated patients.