Disrupted development of the dominant hemisphere following prenatal irradiation

One hundred children, exposed prenatally to radiation after the Chernobyl nuclear power plant accident, and 50 nonexposed classmates were examined between the ages of 11 and 13 years old using neuropsychiatric tests, WISC, EEG, and visual evoked potentials. Individual prenatal radiation doses were reconstructed for all examined children. The exposed children were found to have more neuropsychiatric disorders, left-brain neurological signs, lower full-scale and verbal IQ, IQ discrepancies with verbal decrement, disorganized EEG patterns, an excess of lateralized-to-left frontotemporal region delta and beta power with depression of theta and alpha power, and interhemispheric inversion visual information processing. Mothers' mental health, stress, and prenatal irradiation contributed to these effects, along with several confounding factors.     

Neighborhood-level socioeconomic predictors of nonadherence to mammography screening guidelines.

As neighborhood context is increasingly recognized as an important predictor of health outcomes and health behaviors, this analysis sought to determine the relationship between neighborhood-level socioeconomic status (SES) and regular mammography screening behavior. One thousand four hundred fifty-one women ages 40 to 79 years who obtained an "index" screening mammogram at one of five urban hospitals in Connecticut between October 1996 and January 1998 were enrolled in this prospective study. The logistic regression analysis includes the 1,229 women [484 African-American (39%) and 745 White (61%)] who completed telephone interviews at baseline and follow-up (average 29.4 months later) and for whom the study outcome, nonadherence to age-specific mammography screening guidelines, was ascertained. Neighborhood-level SES was determined using 1990 census tract information. Neighborhood-level SES variables (quartiles) were associated with nonadherence for African-American women [neighborhood-level education and composite socioeconomic position index (SEP Index)] and White women (neighborhood-level crowding and neighborhood-level assets). Using race-specific categorizations reflective of individual-level SES distributions, the SEP Index and neighborhood-level education were associated with nonadherence to mammography screening guidelines for African-American women (marginally significant for White women), independent of individual-level SES and other known predictors of mammography screening use [African-American women: SEP Index odds ratio (OR), 3.55; 95% confidence interval (95% CI), 1.33-9.51; neighborhood-level education OR, 3.21; 95% CI, 1.25-8.26; White women: SEP Index OR, 2.13; 95% CI, 0.97-4.67; neighborhood-level education OR, 2.31; 95% CI, 0.93-5.76]. The results of this analysis underscore the importance of examining neighborhood social context as well as individual factors in the study of mammography screening behavior.     

Genetic and metabolomic analysis of AdeD and AdeI mutants of de novo purine biosynthesis: Cellular models of de novo purine biosynthesis deficiency disorders

Purines are molecules essential for many cell processes, including RNA and DNA synthesis, regulation of enzyme activity, protein synthesis and function, energy metabolism and transfer, essential coenzyme function, and cell signaling. Purines are produced via the de novo purine biosynthesis pathway. Mutations in purine biosynthetic genes, for example phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS, E.C. 6.3.2.6/E.C. 4.1.1.21), can lead to developmental anomalies in lower vertebrates. Alterations in PAICS expression in humans have been associated with various types of cancer. Mutations in adenylosuccinate lyase (ADSL, E.C. 4.3.2.2) or 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC, E.C. 2.1.2.3/E.C. 3.5.4.10) lead to inborn errors of metabolism with a range of clinical symptoms, including developmental delay, severe neurological symptoms, and autistic features. The pathogenetic mechanism is unknown for these conditions, and no effective treatments exist. The study of cells carrying mutations in the various de novo purine biosynthesis pathway genes provides one approach to analysis of purine disorders. Here we report the characterization of AdeD Chinese hamster ovary (CHO) cells, which carry genetic mutations encoding p.E177K and p.W363* variants of PAICS. Both mutations impact PAICS structure and completely abolish its biosynthesis. Additionally, we describe a sensitive and rapid analytical method for detection of purine de novo biosynthesis intermediates based on high performance liquid chromatography with electrochemical detection. Using this technique we detected accumulation of AIR in AdeD cells. In AdeI cells, mutant for the ADSL gene, we detected accumulation of SAICAR and SAMP and, somewhat unexpectedly, accumulation of AIR. This method has great potential for metabolite profiling of de novo purine biosynthesis pathway mutants, identification of novel genetic defects of purine metabolism in humans, and elucidating the regulation of this critical metabolic pathway.     

Six year results of the Rebalance mobile bearing total ankle replacement

BackgroundWe report the outcomes of a prospective consecutive series of 267 total ankle replacements (TARs) using a new mobile bearing Rebalance® prosthesis.MethodsBetween April 2011 and December 2018, 267 consecutive Rebalance® prostheses were implanted in 255 patients at 3 different centers. Estimated survival curves with 95% confidence intervals were produced with the Kaplan–Meier method. 110 ankles were followed for at least 5 years and clinical and radiological outcomes were assessed in 92 of these ankles.ResultsTwenty-one ankles were revised at a mean of 34 (7–60) months. The estimated survival was 90% (95% CI 86–95) at 5 years and 88.3% (95% CI 83.–94 at 6 years. The ankles followed for at least 5 years demonstrated a median Likert score of 1 (1–4). Radiolucent zones were detected in 14% and osteolytic cysts in 3%.ConclusionThe survival rate of the Rebalance prosthesis conforms with other reports of similar designs. The satisfaction rate was high. Radiological zones and osteolytic cysts were found at a lower rate than usually reported for mobile bearing TARs. These results favour further use of this implant.