Ultrasound and histological measurements of dividing membrane thickness in twin gestations.

OBJECTIVE: To determine how prenatal ultrasound measurements of dividing membrane thickness correlate with postnatal histological measurements and chorionicity in twin gestations. METHODS: This was a prospective, longitudinal cohort study of twin gestations. Dividing membrane thickness was measured by transabdominal ultrasound, with the insonation beam both parallel and perpendicular to the membrane, in the second or third trimester, depending on when care was established. Ultrasound examinations were performed every 4 weeks following initial assessment until delivery. Measurements of membrane thickness from the first ultrasound examination were compared with histological measurements after delivery. RESULTS: A total of 45 twin pregnancies (32 dichorionic, 13 monochorionic) were included. Mean gestational age at initial ultrasound examination was 24.1 ± 7.3 weeks. Parallel ultrasound measurements of membrane thickness were 1.6 ± 0.8 mm for monochorionic and 2.5 ± 0.9 mm for dichorionic gestations (P = 0.001). Perpendicular ultrasound measurements were 1.6 ± 0.3 mm for monochorionic and 2.2 ± 0.8 mm for dichorionic gestations (P = 0.009). Inter- and intraobserver reliability of ultrasound measurements were 0.847 and 0.950, respectively. Parallel and perpendicular ultrasound measurements correlated better with each other (R = 0.807, P < 0.001) than with histological measurements of membrane thickness (Rparallel = 0.538, P < 0.001; Rperpendicular = 0.529, P < 0.001). Receiver-operating characteristics curve analyses to predict histological membrane thickness > 50th percentile resulted in an area under the curve (AUC) of 0.828 for parallel (P < 0.001) and 0.874 for perpendicular (P < 0.001) measurements with a cut-off value of 1.9 mm for both approaches. The AUCs for parallel and perpendicular measurements to predict dichorionicity were 0.892 (P < 0.001) and 0.823 (P < 0.001) with cut-off values of 1.9 and 1.8 mm, respectively. CONCLUSION: Prenatal ultrasound measurement of twin dividing membrane thickness is positively correlated with postnatal histological measurement. Dichorionicity can be determined by a magnified dividing membrane thickness ≥ 1.9 mm. Measurements with the ultrasound beam parallel to the dividing membrane may be more accurate than perpendicular measurements. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Adaptive genetic changes related to haemoglobin concentration in native high-altitude Tibetans.

NEW FINDINGS: What is the topic of this review? Tibetans have genetic adaptations that are hypothesized to underlie the distinct set of traits they exhibit at altitude. What advances does it highlight? Several adaptive signatures in the same genomic regions have been identified among Tibetan populations resident throughout the Qinghai-Tibetan Plateau. Many highland Tibetans exhibit a haemoglobin concentration within the range expected at sea level, and this trait is associated with putatively adaptive regions harbouring the hypoxia-inducible factor pathway genes EGLN1, EPAS1 and PPARA. Precise functional variants at adaptive loci and relationships to physiological traits, beyond haemoglobin concentration, are currently being examined in this population. Some native Tibetan, Andean and Ethiopian populations have lived at altitudes ranging from 3000 to >4000 m above sea level for hundreds of generations and exhibit distinct combinations of traits at altitude. It was long hypothesized that genetic factors contribute to adaptive differences in these populations, and recent advances in genomics provide evidence that some of the strongest signatures of positive selection in humans are those identified in Tibetans. Many of the top adaptive genomic regions highlighted thus far harbour genes related to hypoxia sensing and response. Putatively adaptive copies of three hypoxia-inducible factor pathway genes, EPAS1, EGLN1 and PPARA, are associated with sea-level range, rather than elevated, haemoglobin concentration observed in many Tibetans at high altitude, and recent studies provide insight into some of the precise adaptive variants, timing of adaptive events and functional roles. While several studies in highland Tibetans have converged on a few hypoxia-inducible factor pathway genes, additional candidates have been reported in independent studies of Tibetans located throughout the Qinghai-Tibetan Plateau. Various aspects of adaptive significance have yet to be identified, integrated, and fully explored. Given the rapid technological advances and interdisciplinary efforts in genomics, physiology and molecular biology, careful examination of Tibetans and comparisons with other distinctively adapted highland populations will provide valuable insight into evolutionary processes and models for both basic and clinical research.

A novel approach to 3D modelling ground-penetrating radar (GPR) data - A case study of a cemetery and applications for criminal investigation.

Ground-penetrating radar (GPR) is an established geophysical technique used extensively for the accurate reconstruction of the shallow (<10 m) subsurface. Reconstructions have largely been completed and presented as 2D vertical and horizontal planes, leaving limited visualization of subsurface 3D shapes and their spatial relationships. With technological advancements, particularly the availability and integration of various software platforms, 3D modelling of GPR data is now emerging as the new standard. However, despite these developments, there remains an inadequate examination and testing of these techniques, particularly in determining if their application is beneficial and warranted. In this study we conducted a GPR grid survey on a churchyard cemetery to generate and evaluate 2D and 3D-modelled reconstructions of the cemetery burial sites. Data collection and processing was completed using a Sensors and Software Incorporated pulseEKKO™ Pro SmartCart GPR system and EKKO_Project™ software, respectively. The modelling component was achieved using Schlumberger's Petrel™ E & P software platform, which is tailored to the petroleum industry. The subsurface patterns present in the 2D and 3D models closely matched the cemetery plot plan, validating our data collection, processing, and modelling methods. Both models were adequate for 2D horizontal visualization of reflection patterns at any specific depth. The 3D model was used to identify the presence of a companion burial plot (stacked caskets) and possible leachate plumes below and encircling burial sites, both of which were not evident in the 2D model, highlighting the benefits of 3D modelling when discerning subsurface objects. We expect our findings to be of value to similar GPR studies, with particular significance to geoforensic studies and criminal investigations.

Large-scale analysis of acquired chromosomal alterations in non-tumor samples from patients with cancer.

Mosaicism, the presence of subpopulations of cells bearing somatic mutations, is associated with disease and aging and has been detected in diverse tissues, including apparently normal cells adjacent to tumors. To analyze mosaicism on a large scale, we surveyed haplotype-specific somatic copy number alterations (sCNAs) in 1,708 normal-appearing adjacent-to-tumor (NAT) tissue samples from 27 cancer sites and in 7,149 blood samples from The Cancer Genome Atlas. We find substantial variation across tissues in the rate, burden and types of sCNAs, including those spanning entire chromosome arms. We document matching sCNAs in the NAT tissue and the adjacent tumor, suggesting a shared clonal origin, as well as instances in which both NAT tissue and tumor tissue harbor a gain of the same oncogene arising in parallel from distinct parental haplotypes. These results shed light on pan-tissue mutations characteristic of field cancerization, the presence of oncogenic processes adjacent to cancer cells.

The fine structure of the exoerythrocytic stages of Plasmodium fallax.

The fine structure of the exoerythrocytic cycle of an avian malarial parasite, Plasmodium fallax, has been analyzed using preparations grown in a tissue culture system derived from embryonic turkey brain cells which were fixed in glutaraldehyde-OsO(4). The mature merozoite, an elongated cell 3- to 4-micro long and 1- to 2-micro wide, is ensheathed in a complex double-layered pellicle. The anterior end consists of a conoid, from which emanate two lobed paired organelles and several closely associated dense bodies. A nucleus is situated in the mid portion of the cell, while a single mitochondrion wrapped around a spherical body is found in the posterior end. On the pellicle of the merozoite near the nucleus a cytostomal cavity, 80 to 100 mmicro in diameter, is located. Based on changes in fine structure, the subsequent sequence of development is divided into three phases: first, the dedifferentiation phase, in which the merozoite loses many complex structures, i.e. the conoid, paired organelles, dense bodies, spherical body, and the thick inner layers of the pellicle, and transforms into a trophozoite; second, the growth phase, which consists of many nuclear divisions as well as parallel increases in mitochondria, endoplasmic reticulum, and ribosomes; and third, the redifferentiation and cytoplasmic schizogony phase, in which the specialized organelles reappear as the new merozoites bud off from the mother schizont.

Fine structure of the asexual stages of Plasmodium elongatum.

Plasmodium elongatum, an avian malarial parasite, differs from other such parasites by infecting both the circulating red blood cells and the hematopoietic cells. The exoerythrocytic development of P. elongatum occurs mainly in these red cell precursors. The fine structure of the asexual stages of P. elongatum has been studied in the bone marrow and peripheral blood of canaries and compared with that of the asexual stages of other avian malarial parasites. With minor differences, the merozoites of P. elongatum possess the same organelles as those in the exoerythrocytic merozoites of P. fallax and the erythrocytic stages of P. cathemerium, P. lophurae, P. fallax, and P. gallinaceum. The developmental sequence is also essentially similar to that of other avian malarial parasites, in that upon entry into a new host cell, the dedifferentiation, growth, and redifferentiation phases take place. However, we have found some important differences in the feeding mechanism of P. elongatum. The cytostome is involved in the ingestion of host cell cytoplasm in both exoerythrocytic and erythrocytic stages, in contrast to P. fallax, in which the cytostome is inactive in the exoerythrocytic stages. In P. elongatum, host cell cytoplasm is ingested through the cytostome, and "boluses" are formed and incorporated into a large digestive vacuole. Subsequently, the digestion of the boluses takes place in this digestive vacuole. Thus, in regard to the function of the cytostome, the exoerythrocytic stages of P. elongatum appear to be closely related to the erythrocytic stage which has a feeding mechanism similar to that of the erythrocytic stage of other avian malarial parasites.

The feeding mechanism of avian malarial parasites.

Electron microscope studies of the erythrocytic forms, including gametocytes and asexual schizonts, of the protozoa Plasmodium fallax, P. lophurae, and P. cathemerium, have revealed a "cytostome," a specialized organelle of the pellicular membrane which is active in the ingestion of host cell cytoplasm. In material fixed in glutaraldehyde and postfixed in OsO(4), the cytostome appears in face view as a pore limited by two dense circular membranes and having an inside diameter of approximately 190 mmicro. In cross-section, the cytostome is a cavity bounded on each side by two dense segments corresponding to the two dense circles observed in face view; its base consists of a single unit membrane. In the process of feeding, the cytostome cavity enlarges by expansion of its membrane, permitting a large quantity of red cell cytoplasm to come into contact with the cytostome wall. Subsequent digestion of erythrocyte cytoplasm occurs exclusively in food vacuoles which emanate from the cytostome invagination. As digestion progresses, the food vacuoles initially stain more densely and there is a marked build-up of hemozoin granules. In the final stage of digestion, a single membrane surrounds a cluster of residual pigment particles and very little of the original host cell cytoplasm remains. The cytostome in exoerythrocytic stages of P. fallax has been observed only in merozoites and does not seem to play the same role in the feeding mechanism.

Changes in photo-aged human skin following topical application of all-trans retinoic acid.

Although topical applications of retinoids on rodents and humans have been shown to cause epidermal hyperplasia, a detailed study of the influence of retinoids on epidermal differentiation in vivo has not been performed. In order to assess the pharmacologic effects of chronic topical tretinoin application used to improve the appearance of patients with photoaged skin, cutaneous biopsies from 25 patients in a controlled clinical study were examined histologically and immunocytochemically. Chronic application of tretinoin causes epidermal thickening (25 of 25 samples), stratum granulosum thickening (15 of 25), parakeratosis (13 of 25), a marked increase in the number of cell layers expressing epidermal transglutaminase (13 of 25), and focal expression of two keratins, K6 (12 of 25) and K13 (8 of 25), not normally expressed in the epidermis. The morphologic changes correlated with immunohistochemical abnormalities; neither of these correlated with the subjective cosmetic response. Three major epidermal differentiation products, keratins K1, K10, and K14 were not altered, within the limits of the methods used. Thus, chronic topical tretinoin reprograms some, but not all, aspects of human epidermal differentiation in vivo.

Hemoglobin Jackson, alpha 127 (H10) Lys replaced by Asn.

A new hemoglobin mutant was detected as a fast-moving variant on cellulose acetate electrophoresis at pH 8.4. The mutation is in the alpha-chain at position 127, where lysine is substituted by asparagine. This is an external residue, and mutation at this site does not lead to any altered physiologic function of the hemoglobin.

Antiepiligrin cicatricial pemphigoid. A subepithelial bullous disorder.

BACKGROUND: Epiligrin is a glycoprotein complex deposited in extracellular matrix by cultured human keratinocytes that serves as the major integrin ligand of these cells. In human skin, epiligrin is found at the interface of the lamina lucida and lamina densa in epidermal basement membrane where it is believed to be associated with anchoring filaments and plays an important role in keratinocyte adhesion. METHODS AND RESULTS: We have identified six patients with a subepithelial bullous disorder of mucous membranes and skin who have IgG anti-basement membrane autoantibodies that immunoprecipitate epiligrin from human keratinocyte extracts and culture media. These patients' IgG autoantibodies also bind epiligrin in human keratinocyte extracellular matrix and epidermal basement membrane as determined by immunofluorescence and immunoelectron microscopy. Studies of 10 patients who are clinically indistinguishable from subjects with anti-epiligrin autoantibodies (ie, cicatricial pemphigoid patients) found that while seven had anti-basement membrane autoantibodies, the latter are directed exclusively against a region of epidermal basement membrane that does not contain epiligrin, are present in low titer (ie, < or = 1:10), do not react with keratinocyte extracellular matrix, and do not bind epiligrin (or any other specific antigen) in immunoprecipitation studies of human keratinocyte extracts or media. Antiepiligrin autoantibodies were also not detected in studies of 36 additional patients with bullous diseases or six normal volunteers. CONCLUSIONS: Cicatricial pemphigoid is a disease phenotype in which patients' autoantibodies may target different constituents of epidermal basement membrane. Antiepiligrin autoantibodies are a specific immunologic marker for a group of patients with a disease entity that we propose to designate antiepiligrin cicatricial pemphigoid.

Myelodysplasia. The influence of the quadriceps and hip abductor muscles on ambulatory function and stability of the hip.

In an analysis of motor function, ambulatory function, and hip stability in sixty-five patients with myelodysplasia, four motor-function groups based on the strength of the quadriceps and hip abductor muscles were identified. Retrospectively, it was evident that based on these groups, it would have been possible to predict which hips would remain stable, what level of ambulatory function the patients could achieve, and whether treatment to reduce and stabilize the hips was indicated. Fifty-seven of fifty-eight hips in the twenty-nine patients with functioning quadriceps muscles but non-functioning hip-abductor muscles were either subluxated or dislocated. Thirty-nine of the remaining forty-six patients with functioning quadriceps muscles could walk. In this series, three operative procedures were used to treat hip subluxation: varus osteotomy, varus osteotomy combined with iliopsoas transfer, and iliopsoas transfer alone. One shelf procedure was also done. Varus osteotomy was the best procedure for hip subluxation while posterior iliopsoas transfer, either alone or in combination with a varus osteotomy, was of questionable value. Treatment of hip instability (subluxation or dislocation) in patients without quadriceps function was not necessary.

Quantitative applications: forecasting and costing nursing service at an Army community hospital.

The utilization of a quantitative method of forecasting, coupled with an existing patient classification system (the Army's Workload Management System for Nursing), provides a creative costing tool for managing nursing resources at military medical facilities. Although the nursing management options discussed in this article are focused on a downsizing situation at an Army Community Hospital, they are applicable throughout military medical facilities.

Cooperative learning: a model for teaching.

Cooperative learning provides a socially and intellectually stimulating model for the instruction of nursing students. It is one method of encouraging students to take responsibility for their own learning. Students are often able to explain a concept to another student in a unique way not used by faculty. This model harnesses and directs that student input in a constructive manner to increase achievement and accountability for all involved. Faculty must continue to examine how nursing is taught. The world is changing far too rapidly to do "business as usual." Cooperative learning is one strategy that can be used to motivate students to take active and responsible roles in their learning.

Source, recency, and degree of stress in adolescence and suicide ideation.

This study sought to identify factors related to stress that predict suicide ideation among adolescents. The sample consisted of 425 students aged 14 to 18 years. Multiple regression analysis revealed that recency and degree of stress were significant in the prediction of degree and recency of suicide ideation. The implications of these and other findings for prevention and intervention (e.g., health education, parent workshops, and adolescent support groups) are discussed.

Depression in diagnostic subtypes of delinquent boys.

Eighteen percent of the 120 delinquent boys in a training school were found to be depressed when DSM III criteria for Major Depressive Disorder were utilitzed. Contrary to expectations, the prevalence of depression was not significantly more frequent among socialized, undersocialized, aggressive or nonaggressive subtypes. A comparison of depressive symptomatology among the depressed and nondepressed delinquents revealed that psychomotor agitation was not significantly different in the two groups. Over one-third of all parents were depressed and the authors suggest that this could be a contributory factor in the development of delinquency.

The family continuity of care contract.

Continuity of care has been defined as a contract between a patient and physician for medical care. This study looks at continuity of care in a community family practice residency program before and after office contact has been made with at least one member of the family by the assigned physician. It is assumed that during such a visit a contract for care of the family is made. Using this premise, continuity of care increased significantly when the different resident levels and faculty were compared over a 2.5-month period. It seems reasonable to measure the continuity of care provided an assigned family only after a contract has been made. This contract should be accomplished in an initial intake interview or during the initial office contact with the assigned physician.

A net for newborns.

As part of the AHA's Campaign for Coverage, the Delaware Valley Healthcare Council aims to link every baby in the five-county Philadelphia area with its own doctor--regardless of insurance status.

Home-grown health plan.

Most companies in Sullivan County, N.H., employ fewer than five people, so a decade of economic decline meant many could't afford to offer health benefits. Valley Regional Healthcare saw its chance to help out the community, launching an HMO-style plan that keeps control--and spending--local.

Contract balks.

Fed up with insurers dictating contract terms, doctors are fighting back by putting the American Medical Association on the job. Yet the AMA's remedy--a bulky "model" agreement--may lack the power of persuasion.

Back to schools. Phoenix health system finds poor families more trusting of school-based centers.

Low-income families tend to trust school clinics to care for their kids, leading one Phoenix health care executive to ask why the model isn't more common. His system supports five school health centers that treat hundreds of kids too rich for Medicaid, yet too poor for private insurance.