CAnceR IN PreGnancy (CARING) - a retrospective study of cancer diagnosed during pregnancy in the United Kingdom.

BACKGROUND: The incidence of cancer diagnosed during pregnancy is increasing. Data relating to investigation and management, as well as maternal and foetal outcomes is lacking in a United Kingdom (UK) population. METHODS: In this retrospective study we report data from 119 patients diagnosed with cancer during pregnancy from 14 cancer centres in the UK across a five-year period (2016-2020). RESULTS: Median age at diagnosis was 33 years, with breast, skin and haematological the most common primary sites. The majority of cases were new diagnoses (109 patients, 91.6%). Most patients were treated with radical intent (96 patients, 80.7%), however, gastrointestinal cancers were associated with a high rate of palliative intent treatment (63.6%). Intervention was commenced during pregnancy in 68 (57.1%) patients; 44 (37%) had surgery and 31 (26.1%) received chemotherapy. Live births occurred in 98 (81.7%) of the cases, with 54 (55.1%) of these delivered by caesarean section. Maternal mortality during the study period was 20.2%. CONCLUSIONS: This is the first pan-tumour report of diagnosis, management and outcomes of cancer diagnosed during pregnancy in the UK. Our findings demonstrate proof of concept that data collection is feasible and highlight the need for further research in this cohort of patients.

Drought decreases water storage capacity of two arboreal epiphytes with differing ecohydrological traits.

Arboreal epiphytes, plants that grow on trees, can significantly increase rainwater storage and evaporation (i.e., "interception") within canopies. Drought conditions may affect this hydrological role, as epiphytes' physiological responses change leaf properties that affect water retention. Drought-induced changes in epiphyte water storage capacity could substantially alter canopy hydrology, but have not been studied. We tested the effects of drought on the water storage capacity (Smax) of leaves and leaf properties of two epiphytes with distinct ecohydrological traits: resurrection fern (Pleopeltis polypodioides), and Spanish moss (Tillandsia usneoides). Both species are common in maritime forests of the Southeastern USA, where climate change is expected to decrease precipitation in spring and summer. To simulate drought, we dried leaves to 75 %, 50 %, and ~25 % of fresh weight, and quantified their Smax in fog chambers. We measured relevant leaf properties: hydrophobicity, minimum leaf conductance (gmin; a measure of water loss under drought), and Normalized Difference Vegetative Index (NDVI). We found that drought significantly reduced Smax and increased leaf hydrophobicity for both species, indicating that lower Smax may be due to shedding of droplets. While the overall reduction in Smax did not differ between the two species, they exhibited distinct drought responses. Dehydrated T. usneoides leaves had lower gmin, demonstrating the ability to limit water loss under drought. P. polypodioides increased gmin when dehydrated, consistent with its extraordinary ability to withstand water loss. NDVI decreased with dehydration in T. usneoides but not P. polypodioides. Our results suggest that increased drought may have a dramatic effect on canopy water cycling by reducing the Smax of epiphytes. Reduced rainfall interception and storage in forest canopies could have widespread effects on hydrological cycling, thus understanding the potential feedbacks of plant drought response on hydrology is crucial. This study highlights the importance of connecting foliar-scale plant response with broader hydrological processes.

Particle-Size Variability of Aerosol Iron and Impact on Iron Solubility and Dry Deposition Fluxes to the Arctic Ocean.

This study provides unique insights into the properties of iron (Fe) in the marine atmosphere over the late summertime Arctic Ocean. Atmospheric deposition of aerosols can deliver Fe, a limiting micronutrient, to the remote ocean. Aerosol particle size influences aerosol Fe fractional solubility and air-to-sea deposition rate. Size-segregated aerosols were collected during the 2015 US GEOTRACES cruise in the Arctic Ocean. Results show that aerosol Fe had a single-mode size distribution, peaking at 4.4 µm in diameter, suggesting regional dust sources of Fe around the Arctic Ocean. Estimated dry deposition rates of aerosol Fe decreased from 6.1 µmol m-2 yr-1 in the areas of ~56°N-80°N to 0.73 µmol m-2 yr-1 in the areas north of 80°N. Aerosol Fe solubility was higher in fine particles (<1 µm) which were observed mainly in the region north of 80°N and coincided with relatively high concentrations of certain organic aerosols, suggesting interactions between aerosol Fe and organic ligands in the high-latitude Arctic atmosphere. The average molar ratio of Fe to titanium (Ti) was 2.4, substantially lower than the typical crustal ratio of 10. We speculate that dust sources around the Arctic Ocean may have been altered because of climate warming.

Pyrogenic iron: The missing link to high iron solubility in aerosols.

Atmospheric deposition is a source of potentially bioavailable iron (Fe) and thus can partially control biological productivity in large parts of the ocean. However, the explanation of observed high aerosol Fe solubility compared to that in soil particles is still controversial, as several hypotheses have been proposed to explain this observation. Here, a statistical analysis of aerosol Fe solubility estimated from four models and observations compiled from multiple field campaigns suggests that pyrogenic aerosols are the main sources of aerosols with high Fe solubility at low concentration. Additionally, we find that field data over the Southern Ocean display a much wider range in aerosol Fe solubility compared to the models, which indicate an underestimation of labile Fe concentrations by a factor of 15. These findings suggest that pyrogenic Fe-containing aerosols are important sources of atmospheric bioavailable Fe to the open ocean and crucial for predicting anthropogenic perturbations to marine productivity.

Vitamin D status and bone mineral density in African American children with Crohn disease.

BACKGROUND: Vitamin D deficiency and low bone mineral density (BMD) are complications of inflammatory bowel disease. Vitamin D deficiency is more prevalent among African Americans compared with whites. There are little data comparing differences in serum 25-hydroxyvitamin D (25OHD) concentrations and BMD between African American and white children with Crohn disease (CD). METHODS: We compared serum 25OHD concentrations of African American children with CD (n = 52) to white children with CD (n = 64) and healthy African American controls (n = 40). We also analyzed BMD using dual-energy x-ray absorptiometry results from our pediatric CD population. RESULTS: African American children with CD had lower serum 25OHD concentrations (16.1 [95% confidence interval, CI 14.5-17.9] ng/mL) than whites with CD (22.3 [95% CI 20.2-24.6] ng/mL; P < 0.001). African Americans with CD and controls exhibited similar serum 25OHD concentration (16.1 [95% CI 14.5-17.9] vs 16.3 [95% CI 14.4-18.4] ng/mL; NS). African Americans with CD exhibited no difference in serum 25OHD concentration when controlling for seasonality, disease severity, and surgical history, although serum 25OHD concentration was significantly decreased in overweight children (body mass index ≥85%, P = 0.003). Multiple regression analysis demonstrated that obese African American girls with CD had the lowest serum 25OHD concentrations (9.6 [95% CI 6.8-13.5] ng/mL). BMD was comparable between African American and white children with CD (z score -0.4 ± 0.9 vs -0.7 ± 1.2; NS). CONCLUSIONS: African American children with CD are more likely to have vitamin D deficiency compared with white children with CD, but have similar BMD. CD disease severity and history of surgery do not affect serum 25OHD concentrations among African American children with CD. African American children have low serum 25OHD concentrations, independent of CD, compared with white children. Future research should focus on how race affects vitamin D status and BMD in children with CD.

Isolation and characterization of dendritic cells and macrophages from the mouse intestine.

Within the intestine reside unique populations of innate and adaptive immune cells that are involved in promoting tolerance towards commensal flora and food antigens while concomitantly remaining poised to mount inflammatory responses toward invasive pathogens. Antigen presenting cells, particularly DCs and macrophages, play critical roles in maintaining intestinal immune homeostasis via their ability to sense and appropriately respond to the microbiota. Efficient isolation of intestinal DCs and macrophages is a critical step in characterizing the phenotype and function of these cells. While many effective methods of isolating intestinal immune cells, including DCs and macrophages, have been described, many rely upon long digestions times that may negatively influence cell surface antigen expression, cell viability, and/or cell yield. Here, we detail a methodology for the rapid isolation of large numbers of viable, intestinal DCs and macrophages. Phenotypic characterization of intestinal DCs and macrophages is carried out by directly staining isolated intestinal cells with specific fluorescence-labeled monoclonal antibodies for multi-color flow cytometric analysis. Furthermore, highly pure DC and macrophage populations are isolated for functional studies utilizing CD11c and CD11b magnetic-activated cell sorting beads followed by cell sorting.

Acute methotrexate toxicity seen as plaque psoriasis ulceration and necrosis: A diagnostic clue.

In addition to the well-known signs of methotrexate toxicity, rare cutaneous side effects have been described. These cutaneous signs may provide a diagnostic clue into the diagnosis of toxicity as well as facilitate early and aggressive therapy. We describe the case of a 37-year-old male, with a diagnosis of psoriasis, who developed characteristic signs and symptoms of acute methotrexate toxicity after receiving an unknown amount of intravenous methotrexate. The patient experienced a distinct change in the morphology of his existing psoriatic plaques, which became ulcerated and necrotic in the week following the methotrexate injection. Shortly after the development of cutaneous erosions, the patient developed pancytopenia, which ultimately led to his death. Ulceration and necrosis of cutaneous psoriasis plaques may serve as a herald for the impending development of life-threatening pancytopenia in patients with acute methotrexate toxicity.

Severe eye injuries in the war in Iraq, 2003-2005.

PURPOSE: To document the incidence and treatment of patients with severe ocular and ocular adnexal injuries during Operation Iraqi Freedom. DESIGN: Retrospective hospital-based observational analysis of injuries. PARTICIPANTS: All coalition forces, enemy prisoners of war, and civilians with severe ocular and ocular adnexal injuries. METHODS: The authors retrospectively examined severe ocular and ocular adnexal injuries that were treated by United States Army ophthalmologists during the war in Iraq from March 2003 through December 2005. MAIN OUTCOME MEASURES: Incidence, causes, and treatment of severe ocular and ocular adnexal injuries. RESULTS: During the time data were gathered, 797 severe eye injuries were treated. The most common cause of the eye injuries was explosions with fragmentation injury. Among those injured, there were 438 open globe injuries, of which 49 were bilateral. A total of 116 eyes were removed (enucleation, evisceration, or exenteration), of which 6 patients required bilateral enucleation. Injuries to other body systems were common. CONCLUSIONS: Severe eye injuries represent a significant form of trauma encountered in Operation Iraqi Freedom. These injuries were most commonly caused by explosion trauma.

Device for simulating anterior segment surgery.

To provide a more realistic method for practicing anterior segment surgery, a device was designed that incorporates aspects of currently available cadaver globe fixation methods. A Styrofoam head was fitted with a funnel and tubing system that allows for direct application of variable external suction to a globe placed in an artificial socket. Prototypes were tested in a wet lab environment, which demonstrated that this method provides reliable globe fixation and allows for variable control of intraocular pressure during a variety of anterior and posterior segment surgical techniques.

Gaze-evoked amaurosis: a report of five cases.

OBJECTIVE: To highlight the various causes of gaze-evoked amaurosis. DESIGN: Retrospective noncomparative interventional case series. PARTICIPANTS: Five patients treated at our facility over the past 6 years. METHODS: Clinical presentation, radiologic studies, surgical management, and postsurgical results are presented. MAIN OUTCOME MEASURES: Visual acuity, clinical findings of gaze-evoked amaurosis. RESULTS: Only two patients had classic intraorbital etiologies, one with an intraconal cavernous hemangioma and one with an intraconal foreign body. Three patients had extraorbital processes, two with orbital fractures and one with a sinus tumor. Only two of our patients initially were aware of the gaze-evoked amaurosis at presentation. Appropriate surgery was curative in all cases. CONCLUSIONS: Gaze-evoked amaurosis is a rare condition, classically implicating intraconal orbital pathology. In one of the largest case series published to date, we found extraorbital etiologies are also capable of producing gaze-evoked vision loss. Gaze-evoked amaurosis should be suspected and tested for in any orbital condition.

Warm balanced salt solution for clearing tear film precipitation during cataract surgery.

Adequate anterior segment visualization during cataract surgery can be hindered when excessive tear film secretions precipitate on the corneal surface before the initial corneal incision is made. In most cases, room-temperature balanced salt solution applied to the corneal surface clears the debris. However, in cases in which tear film precipitates persist after the use of room-temperature balanced salt solution, the application of warm balanced salt solution can provide rapid and sustained dispersion of the precipitates. We present our experience using this technique.

Analyses of the cag pathogenicity island of Helicobacter pylori.

Most strains of Helicobacter pylori from patients with peptic ulcer disease or intestinal-type gastric cancer carry cagA, a gene that encodes an immunodominant protein of unknown function, whereas many of the strains from asymptomatically infected persons lack this gene. Recent studies showed that the cagA gene lies near the right end of a approximately 37kb DNA segment (a pathogenicity island, or PAI) that is unique to cagA+ strains and that the cag PAI was split in half by a transposable element insertion in the reference strain NCTC11638. In complementary experiments reported here, we also found the same cag PAI, and sequenced a 39 kb cosmid clone containing the left 'cagII' half of this PAI. Encoded in cagII were four proteins each with homology to four components of multiprotein complexes of Bordetella pertussis ('Ptl'), Agrobacterium tumefaciens ('Vir'), and conjugative plasmids ('Tra') that help deliver pertussis toxin and T (tumour inducing) and plasmid DNA, respectively, to target eukaryotic or prokaryotic cells, and also homologues of eukaryotic proteins that are involved in cytoskeletal structure. To the left of cagII in this cosmid were genes for homologues of HsIU (heat-shock protein) and Era (essential GTPase); to the right of cagII were homologues of genes for a type I restriction endonuclease and ion transport functions. Deletion of the cag PAI had no effect on synthesis of the vacuolating cytotoxin, but this deletion and several cag insertion mutations blocked induction of synthesis of proinflammatory cytokine IL-8 in gastric epithelial cells. Comparisons among H. pylori strains indicated that cag PAI gene content and arrangement are rather well conserved. We also identified two genome rearrangements with end-points in the cag PAI. One, in reference strain NCTC11638, involved IS605, a recently described transposable element (as also found by others). Another rearrangement, in 3 of 10 strains tested (including type strain NCTC11637), separated the normally adjacent cagA and picA genes and did not involve IS605. Our results are discussed in terms of how cag-encoded proteins might help trigger the damaging inflammatory responses in the gastric epithelium and possible contributions of DNA rearrangements to genome evolution.

Characterization of the mouse beta-prime adaptin gene; cDNA sequence, genomic structure, and chromosomal localization.

Adaptins are important subunits of heterotetrameric complexes called adaptors, which participate in the clathrin-coated, vesicle-mediated endocytosis and intracellular receptor transport. The gene family of adaptins is divided into three classes, alpha, beta, and gamma, with further subdivision into beta- and beta-prime components. Two beta-prime adaptins, the rat AP105a and the human BAM22, have previously been characterized. The BAM22 gene is located on human Chromosome (Chr) 22q12 and can be considered a candidate meningioma tumor suppressor gene. We report here the characterization of the mouse ortholog of the BAM22 gene, and we suggest the name adtb1 for the mouse gene. Like the BAM22 gene, the adtb1 transcript is highly and ubiquitously expressed. We provide 3885-bp cDNA sequence, which entirely covers the open reading frame of the adtb1, capable of encoding a protein of 943 amino acids. The adtb1 protein is highly conserved (>96% identity) when compared with AP105a and BAM22 proteins. We also report the genomic organization of adtb1, which is similar to the BAM22 gene. The adtb1 gene has been assigned to mouse Chr 11, band 11A2, which confirms the synteny between human Chr 22q12 and mouse Chr 11.

Kahalalides: Bioactive Peptides from a Marine Mollusk Elysia rufescens and Its Algal Diet Bryopsis sp.(1).

In addition to the previously reported bioactive kahalalide F six new peptides are described. Six of these, including kahalalide F, are cyclic depsipeptides, ranging from a C(31) tripeptide to a C(75) tridecapeptide isolated from a sacoglossan mollusk, Elysiarufescens. The mollusk feeds on a green alga, Bryopsis sp., which has also been shown to elaborate some of these peptides in smaller yields, in addition to an acyclic analog of F, kahalalide G. The bioassay results of antitumor, antiviral, antimalarial, and OI (activity against AIDS opportunistic infections) tests are reported.

Structure of the promoter and genomic organization of the human beta'-adaptin gene (BAM22) from chromosome 22q12.

Adaptins are major structural components of heterotetrameric protein complexes called adaptors, which are essential in intracellular receptor transport via clathrin-coated vesicles. beta-adaptins constitute one of three known classes (alpha, beta, gamma) of adaptins, including beta and beta' subtypes. We previously cloned the human beta'-adaptin gene (BAM22) (GDB symbol, ADTB1) from chromosome 22q12 and proposed its involvement in the development of meningiomas. Here we describe the genomic organization of this gene, which consists of 22 exons spanning over approximately 100 kb. We also report results from point mutation screening of 7 randomly chosen exons analyzed in 110 sporadic meningiomas. As part of the genomic characterization of the BAM22 locus, we sequenced 40 kb covering exons 1-4 and 12 kb upstream from the start of gene transcription. Analysis of the sequence suggests that the BAM22 gene has a CG-rich promoter.

Sequence and analysis of the human ABL gene, the BCR gene, and regions involved in the Philadelphia chromosomal translocation.

The complete human BCR gene (152-141 nt) on chromosome 22 and greater than 80% of the human ABL gene (179-512 nt) on chromosome 9 have been sequenced from mapped cosmid and plasmid clones via a shotgun strategy. Because these two chromosomes are translocated with breakpoints within the BCR and ABL genes in Philadelphia chromosome-positive leukemias, knowledge of these sequences also might provide insight into the validity of various theories of chromosomal rearrangements. Comparison of these genes with their cDNA sequences reveal the positions of 23 BCR exons and putative alternative BCR first and second exons, as well as the common ABL exons 2-11, respectively. Additionally, these regions include the alternative ABL first exons 1b and 1a, a new gene 5' to the first ABL exon, and an open reading frame with homology to an EST within the BCR fourth intron. Further analysis reveals an Alu homology of 38.83 and 39.35% for the BCR and ABL genes, respectively, with other repeat elements present to a lesser extent. Four new Philadelphia chromosome translocation breakpoints from chronic myelogenous leukemia patients also were sequenced, and the positions of these and several other previously sequenced breakpoints now have been mapped precisely, although no consistent breakpoint features immediately were apparent. Comparative analysis of genomic sequences encompassing the murine homologues to the human ABL exons 1b and 1a, as well as regions encompassing the ABL exons 2 and 3, reveals that although there is a high degree of homology in their corresponding exons and promoter regions, these two vertebrate species show a striking lack of homology outside these regions.

The complete nucleotide sequences of the SacBII Kan domain of the P1 pAD10-SacBII cloning vector and three cosmid cloning vectors: pTCF, svPHEP, and LAWRIST16.

The complete nucleotide sequence of the 16,009-bp SacBII Kan domain of the P1 pAD10-SacBII cloning vector and the sequences of three cosmid cloning vectors, pTCF (7941 bp), svPHEP (9201 bp), and LAWRIST16 (5194 bp) have been determined. A modified diatomaceous earth (Prep-A-Gene)-based procedure, which rapidly yields highly supercoiled double-stranded DNA from recombinant P1 and cosmid clones suitable for generating shotgun libraries, also has been developed. The isolated recombinant DNAs were physically sheared to generate 1- to 2-kb fragments that then were blunt-ended and subcloned into double-stranded pUC-based sequencing vectors. The double-stranded sequencing templates were isolated by an alkaline lysis method and subjected to Taq polymerase catalyzed fluorescent end-labeled primer cycle sequencing. After shotgun sequence assembly, contig gaps were closed and ambiguities were resolved via Sequenase catalyzed fluorescent dye-terminator sequencing.

Experimental infection of broiler and Leghorn chickens with virulent and avirulent isolates of hemorrhagic enteritis virus.

The effects of virulent and avirulent isolates of hemorrhagic enteritis virus were studied in Leghorn and broiler chickens. The viruses caused subclinical infections in both strains of birds. The avirulent isolate produced enlarged spleens, inclusion bodies, and antibody in all inoculated Leghorns. In broilers the avirulent virus produced infection in only half of the inoculated birds. Inclusion bodies were widely dispersed in the spleens of both types of birds. The virulent virus produced infection in all inoculated birds of both strains. Inclusion bodies were numerous in the spleens of Leghorn birds and were widely scattered in the spleens of broilers.