Aspects of the normal human breast

Studies have been made on normal tissue from 50 whole breasts and 43 breast biopsies using subgross histological and duct injection techniques. The results obtained from the various investigations have been compared with factors which may affect the breast, notably age, the menstrual cycle, parity and laterality. It has been found that the ducts in the breast do not branch in a simple dichotomous manner, nor are individual lactiferous systems arranged about the nipple in discrete lobes like the spokes of a wheel. Rather, the duct systems are interwoven with each other in an intricate manner and may not be dissected out individually. The quantity of parenchymatous lobules in the breast was found to decrease significantly with age. Lobules occurred in areas of high focal density and their number was not related to the amount of fibrous stroma present. Lobules did not occur with greater frequency in the upper outer quadrant of the breast and lobule number was not related to tumour incidence. Parity and laterality were without significance in the present study. The presence of acid mucopolysaccharides in the intra-lobular breast stroma showed a cyclical variation which peaked at approx¬ imately day 24 of the menstrual cycle. It is suggested that hyaluronic acid is the principal component of the staining reaction and may be associated with premenstrual water retention in the breast. The incidence of intraluminal secretions within the ductules of lobules, and intracellular granules within ductular cells, did not reveal cyclical variation. Normal lobule types occurring in whole breasts were assessed by subgross techniques and significant variations were recorded with age. Parity and laterality were not of significance in these results. Examination of breasts following injection of lactiferous ducts with a radio-opaque medium indicated that more than one subgross lobule type was associated with a single lactiferous duct system. Comparisons have been made between the radiographic and subgross morphology of slices of breast tissue and results suggest that the parenchymal content of the breast cannot be predicted from radiographic appearances alone

Education in Time: Cohort Differences in Educational Attainment in African-American Twins

OBJECTIVES:Educational opportunities for African-Americans expanded throughout the 20(th) century. Twin pairs are an informative population in which to examine changes in educational attainment because each twin has the same parents and childhood socioeconomic status. We hypothesized that correlation in educational attainment of older twin pairs would be higher compared to younger twin pairs reflecting changes in educational access over time and potentially reflecting a "ceiling effect" associated with Jim Crow laws and discrimination. METHODOLOGY AND PRINCIPAL FINDINGS:We used data from 211 same-sex twin pairs (98 identical, 113 fraternal) in the Carolina African-American Twin Study of Aging who were identified through birth records. Participants completed an in-person interview. The twins were predominantly female (61%), with a mean age of 50 years (SD = 0.5). We found that older age groups had a stronger intra-twin correlation of attained educational level. Further analysis across strata revealed a trend across zygosity, with identical twins demonstrating more similar educational attainment levels than did their fraternal twin counterparts, suggesting a genetic influence. DISCUSSION:These findings suggest that as educational opportunities broadened in the 20th century, African-Americans gained access to educational opportunities that better matched their individual abilities

Shallow-water hydrothermal venting linked to the Palaeocene–Eocene Thermal Maximum

The Palaeocene–Eocene Thermal Maximum (PETM) was a global warming event of 5–6 °C around 56 million years ago caused by input of carbon into the ocean and atmosphere. Hydrothermal venting of greenhouse gases produced in contact aureoles surrounding magmatic intrusions in the North Atlantic Igneous Province have been proposed to play a key role in the PETM carbon-cycle perturbation, but the precise timing, magnitude and climatic impact of such venting remains uncertain. Here we present seismic data and the results of a five-borehole transect sampling the crater of a hydrothermal vent complex in the Northeast Atlantic. Stable carbon isotope stratigraphy and dinoflagellate cyst biostratigraphy reveal a negative carbon isotope excursion coincident with the appearance of the index taxon Apectodinium augustum in the vent crater, firmly tying the infill to the PETM. The shape of the crater and stratified sediments suggests large-scale explosive gas release during the initial phase of vent formation followed by rapid, but largely undisturbed, diatomite-rich infill. Moreover, we show that these vents erupted in very shallow water across the North Atlantic Igneous Province, such that volatile emissions would have entered the atmosphere almost directly without oxidation to CO2 and at the onset of the PETM

Bi-allelic loss-of-function OBSCN variants predispose individuals to severe recurrent rhabdomyolysis

Rhabdomyolysis is the acute breakdown of skeletal myofibres in response to an initiating factor, most commonly toxins and over exertion. A variety of genetic disorders predispose to rhabdomyolysis through different pathogenic mechanisms, particularly in patients with recurrent episodes. However, most cases remain without a genetic diagnosis. Here we present six patients who presented with severe and recurrent rhabdomyolysis, usually with onset in the teenage years; other features included a history of myalgia and muscle cramps. We identified 10 bi-allelic loss-of-function variants in the gene encoding obscurin (OBSCN) predisposing individuals to recurrent rhabdomyolysis. We show reduced expression of OBSCN and loss of obscurin protein in patient muscle. Obscurin is proposed to be involved in sarcoplasmic reticulum function and Ca2+ handling. Patient cultured myoblasts appear more susceptible to starvation as evidenced by a greater decreased in sarcoplasmic reticulum Ca2+ content compared to control myoblasts. This likely reflects a lower efficiency when pumping Ca2+ back into the sarcoplasmic reticulum and/or a decrease in Ca2+ sarcoplasmic reticulum storage ability when metabolism is diminished. OSBCN variants have previously been associated with cardiomyopathies. None of the patients presented with a cardiomyopathy and cardiac examinations were normal in all cases in which cardiac function was assessed. There was also no history of cardiomyopathy in first degree relatives, in particular in any of the carrier parents. This cohort is relatively young, thus follow-up studies and the identification of additional cases with bi-allelic null OBSCN variants will further delineate OBSCN-related disease and the clinical course of disease. Cabrera-Serrano et al. show that biallelic loss-of-function variants in the gene encoding obscurin (OBSCN) predispose individuals to recurrent and severe episodes of rhabdomyolysis, typically with onset in the teenage years.Peer reviewe

Genomic autopsy to identify underlying causes of pregnancy loss and perinatal death

Pregnancy loss and perinatal death are devastating events for families. We assessed ‘genomic autopsy’ as an adjunct to standard autopsy for 200 families who had experienced fetal or newborn death, providing a defnitive or candidate genetic diagnosis in 105 families. Our cohort provides evidence of severe atypical in utero presentations of known genetic disorders and identifes novel phenotypes and disease genes. Inheritance of 42% of defnitive diagnoses were either autosomal recessive (30.8%), X-linked recessive (3.8%) or autosomal dominant (excluding de novos, 7.7%), with risk of recurrence in future pregnancies. We report that at least ten families (5%) used their diagnosis for preimplantation (5) or prenatal diagnosis (5) of 12 pregnancies. We emphasize the clinical importance of genomic investigations of pregnancy loss and perinatal death, with short turnaround times for diagnostic reporting and followed by systematic research follow-up investigations. This approach has the potential to enable accurate counseling for future pregnancies