Antepartum transabdominal amnioinfusion in oligohydramnios - a comparative study

Background: The purpose of this study was to evaluate the role of antepartum transabdominal amnioinfusion in oligohydramnios with the view to improving pregnancy outcome in oligohydramnios, a serious complication of pregnancy that is associated with a poor perinatal outcome and complicates 1-5% of pregnancies.Methods: The study comprised of a prospective analysis of 130 pregnant women with oligohydramnios, divided into two groups, the study and control group of 65 patients each and were similar with regard to age, gravidity, parity, gestational age. TAA was performed on all patients in the study group and the results were compared and analyzed.Results: Mean gestational age at first treatment was 29.98 weeks in study group. Mean pre-procedure amniotic fluid index was 4.01 and post-procedure was 12.49. A total of 106 infusions were done on 65 patients (mean1.63). Mean latency period in study group was 49.53 and in controls 26.49. There was significant decrease in fetal distress in patients in study group. 30 % of patients needed caesarean section in study group compared to 60% in controls. Number of preterm deliveries was 18 and 45 respectively in study and control groups. 61% of newborns in the study group weighed more than 2.5 kg compared to only 24% in control group. Neonatal ICU admissions and newborn deaths were lesser in study group.Conclusions: Transabdominal amnioinfusion is an extremely useful procedure to reduce complications arising from oligohyramnios. It significantly increases the latency period, decreases the occurrence of fetal distress preterm deliveries, need for caesarean or instrumental deliveries, improves birth weight of the newborns and significantly reduces the neonatal morbidity and mortality

Mechanisms controlling giant sea salt aerosol size distributions along a tropical orographic coastline

Sea salt aerosol (SSA) is a naturally occurring phenomenon that arises from the breaking of waves and consequent bubble bursting on the ocean's surface. The resulting particles exhibit a bimodal distribution spanning orders of magnitude in size that introduces significant uncertainties when estimating the total annual mass of SSA on a global scale. Although estimates of mass and volume are significantly influenced by the presence of giant particles (dry radius &gt;1 µm), effectively observing and quantifying these particles proves to be challenging. Additionally, uncertainties persist regarding the contribution of SSA production along coastlines, but preliminary studies suggest that coastal interactions may increase SSA particle concentrations by orders of magnitude. Moreover, our knowledge regarding the vertical distribution of SSA particles in the marine boundary layer remains limited, resulting in significant gaps in understanding the vertical mixing of giant aerosol particles and specific environmental conditions facilitating their dispersion. By addressing these uncertainties, particularly in regions where SSA particles constitute a substantial percentage of total aerosol loading, we can enhance our comprehension of the complex relationships between the air, sea, aerosols, and clouds. A case study conducted on the Hawaiian island of O`ahu offers insight into the influence of coastlines and orography on the production and vertical distribution of giant SSA size distributions. Along the coastline, the frequency of breaking waves is accelerated, serving as an additional source of SSA production. Furthermore, the steep island orography generates strong and consistent uplift under onshore trade wind conditions, facilitating vertical mixing of SSA particles along windward coastlines. To investigate this phenomenon, in situ measurements of SSA size distributions for particles with dry radii (rd) ≥ 2.8 µm were conducted for various altitudes, ranging from approximately 80 to 650 m altitude along the windward coastline and from 80 to 250 m altitude aboard a ship offshore. Comparing size distributions onshore and offshore confirmed significantly higher concentrations along the coastline, with 2.7–5.4 times greater concentrations than background open-ocean concentrations for supermicron particles. These size distributions were then analyzed in relation to environmental variables influencing SSA production and atmospheric dynamics. It was found that significant wave height exhibited the strongest correlation with changes in SSA size distributions. Additionally, simulated sea salt particle trajectories provided valuable insight into how production distance from the coastline impacts the horizontal and vertical advection of SSA particles of different sizes under varying trade wind speeds. Notably, smaller particles demonstrated reduced dependence on local wind speeds and production distance from the coastline, experiencing minimal dry deposition and high average maximum altitudes relative to larger particles. This research not only highlights the role of coastlines in enhancing the presence and vertical mixing potential of giant SSA particles, but also emphasizes how important it is to consider the influence of local factors on aerosol observations at different altitudes.</p

Transcriptional Regulator CNOT3 Defines an Aggressive Colorectal Cancer Subtype.

Cancer cells exhibit dramatic alterations of chromatin organization at cis-regulatory elements, but the molecular basis, extent, and impact of these alterations are still being unraveled. Here, we identify extensive genome-wide modification of sites bearing the active histone mark H3K4me2 in primary human colorectal cancers, as compared with corresponding benign precursor adenomas. Modification of certain colorectal cancer sites highlighted the activity of the transcription factor CNOT3, which is known to control self-renewal of embryonic stem cells (ESC). In primary colorectal cancer cells, we observed a scattered pattern of CNOT3 expression, as might be expected for a tumor-initiating cell marker. Colorectal cancer cells exhibited nuclear and cytoplasmic expression of CNOT3, suggesting possible roles in both transcription and mRNA stability. We found that CNOT3 was bound primarily to genes whose expression was affected by CNOT3 loss, and also at sites modulated in certain types of colorectal cancers. These target genes were implicated in ESC and cancer self-renewal and fell into two distinct groups: those dependent on CNOT3 and MYC for optimal transcription and those repressed by CNOT3 binding and promoter hypermethylation. Silencing CNOT3 in colorectal cancer cells resulted in replication arrest. In clinical specimens, early-stage tumors that included >5% CNOT3(+) cells exhibited a correlation to worse clinical outcomes compared with tumors with little to no CNOT3 expression. Together, our findings implicate CNOT3 in the coordination of colonic epithelial cell self-renewal, suggesting this factor as a new biomarker for molecular and prognostic classification of early-stage colorectal cancer. Cancer Res; 77(3); 766-79. ©2016 AACR

Genetic Susceptibility Loci of Idiopathic Interstitial Pneumonia do not Represent Risk for Systemic Sclerosis: a Case Control Study in Caucasian Patients

Background: Systemic sclerosis (SSc)-related interstitial lung disease (ILD) has phenotypic similarities to lung involvement in idiopathic interstitial pneumonia (IIP). We aimed to assess whether genetic susceptibility loci recently identified in the large IIP genome-wide association studies (GWASs) were also risk loci for SSc overall or severity of ILD in SSc. Methods: A total of 2571 SSc patients and 4500 healthy controls were investigated from the US discovery GWAS and additional US replication cohorts. Thirteen IIP-related selected single nucleotide polymorphisms (SNPs) were genotyped and analyzed for their association with SSc. Results: We found an association of SSc with the SNP rs6793295 in the LRRC34 gene (OR = 1.14, CI 95 % 1.03 to 1.25, p value = 0.009) and rs11191865 in the OBFC1 gene (OR = 1.09, CI 95 % 1.00 to 1.19, p value = 0.043) in the discovery cohort. Additionally, rs7934606 in MUC2 (OR = 1.24, CI 95 % 1.01 to 1.52, p value = 0.037) was associated with SSc-ILD defined by imaging. However, these associations failed to replicate in the validation cohort. Furthermore, SNPs rs2076295 in DSP ( β = -2.29, CI 95 % -3.85 to -0.74, p value = 0.004) rs17690703 in SPPL2C ( β = 2.04, CI 95 % 0.21 to 3.88, p value = 0.029) and rs1981997 in MAPT ( β = 2.26, CI 95 % 0.35 to 4.17, p value = 0.02) were associated with percent predicted forced vital capacity (FVC%) even after adjusting for the anti-topoisomerase (ATA)-positive subset. However, these associations also did not replicate in the validation cohort. Conclusions: Our results add new evidence that SSc and SSc-related ILD are genetically distinct from IIP, although they share phenotypic similarities

Subependymal giant cell astrocytomas are characterized by mTORC1 hyperactivation, a very low somatic mutation rate, and a unique gene expression profile

Subependymal giant-cell astrocytomas (SEGAs) are slow-growing brain tumors that are a hallmark feature seen in 5–10% of patients with Tuberous Sclerosis Complex (TSC). Though histologically benign, they can cause serious neurologic symptoms, leading to death if untreated. SEGAs consistently show biallelic loss of TSC1 or TSC2. Herein, we aimed to define other somatic events beyond TSC1/TSC2 loss and identify potential transcriptional drivers that contribute to SEGA formation. Paired tumor-normal whole-exome sequencing was performed on 21 resected SEGAs from 20 TSC patients. Pathogenic variants in TSC1/TSC2 were identified in 19/21 (90%) SEGAs. Copy neutral loss of heterozygosity (size range: 2.2–46 Mb) was seen in 76% (16/21) of SEGAs (44% chr9q and 56% chr16p). An average of 1.4 other somatic variants (range 0–7) per tumor were identified, unlikely of pathogenic significance. Whole transcriptome RNA-sequencing analyses revealed 190 common differentially expressed genes in SEGA (n = 16, 13 from a prior study) in pairwise comparison to each of: low grade diffuse gliomas (n = 530) and glioblastoma (n = 171) from The Cancer Genome Atlas (TCGA) consortium, ganglioglioma (n = 10), TSC cortical tubers (n = 15), and multiple normal tissues. Among these, homeobox transcription factors (TFs) HMX3, HMX2, VAX1, SIX3; and TFs IRF6 and EOMES were all expressed >12-fold higher in SEGAs (FDR/q-value < 0.05). Immunohistochemistry supported the specificity of IRF6, VAX1, SIX3 for SEGAs in comparison to other tumor entities and normal brain. We conclude that SEGAs have an extremely low somatic mutation rate, suggesting that TSC1/TSC2 loss is sufficient to drive tumor growth. The unique and highly expressed SEGA-specific TFs likely reflect the neuroepithelial cell of origin, and may also contribute to the transcriptional and epigenetic state that enables SEGA growth following two-hit loss of TSC1 or TSC2 and mTORC1 activation

The specter of empty countrysides and wetlands—Impact of hunting take on birds in Indo-Burma

Hunting for the wild meat trade, medicines and other human uses has decimated Indo-Burma's vertebrate biota and has led to widespread defaunation. Yet, there is surprisingly little data on how hunting impacts wild bird assemblages in different landscapes here. Based on concurrent snapshot surveys of bird hunting, food markets and hunting attitudes across six Indo-Burma countries, we found that hunting threatens species not only in forested landscapes but also wetlands and farmlands such as orchards and paddy fields—ecosystems overlooked by past studies, with at least 47 species associated with wetlands and agricultural lands identified from market surveys across the region. High rates of mortality are suffered when hunting tools such as nets are used to exclude perceived bird pests in both aquaculture and agricultural landscapes, with over 300 individual carcasses of at least 29 identifiable species detected in one aquaculture landscape sampled in Thailand. We warn that the potentially unsustainable trapping of species for consumption and trade in Indo-Burma, coupled with high incidental mortalities, could decimate the populations of erstwhile common and/or legally unprotected species. There is an urgent need for stronger regulatory oversight on the hunting take of wild birds and the use of hunting tools such as nets. Alongside this, conservation practitioners need to better engage with rural communities to address unsustainable hunting practices, especially outside of protected areas

Broad chromosomal domains of histone modification patterns in C. elegans

Chromatin immunoprecipitation identifies specific interactions between genomic DNA and proteins, advancing our understanding of gene-level and chromosome-level regulation. Based on chromatin immunoprecipitation experiments using validated antibodies, we define the genome-wide distributions of 19 histone modifications, one histone variant, and eight chromatin-associated proteins in Caenorhabditis elegans embryos and L3 larvae. Cluster analysis identified five groups of chromatin marks with shared features: Two groups correlate with gene repression, two with gene activation, and one with the X chromosome. The X chromosome displays numerous unique properties, including enrichment of monomethylated H4K20 and H3K27, which correlate with the different repressive mechanisms that operate in somatic tissues and germ cells, respectively. The data also revealed striking differences in chromatin composition between the autosomes and between chromosome arms and centers. Chromosomes I and III are globally enriched for marks of active genes, consistent with containing more highly expressed genes, compared to chromosomes II, IV, and especially V. Consistent with the absence of cytological heterochromatin and the holocentric nature of C. elegans chromosomes, markers of heterochromatin such as H3K9 methylation are not concentrated at a single region on each chromosome. Instead, H3K9 methylation is enriched on chromosome arms, coincident with zones of elevated meiotic recombination. Active genes in chromosome arms and centers have very similar histone mark distributions, suggesting that active domains in the arms are interspersed with heterochromatin-like structure. These data, which confirm and extend previous studies, allow for in-depth analysis of the organization and deployment of the C. elegans genome during development

Mechanisms of Response and Resistance to Combined Decitabine and Ipilimumab for Advanced Myeloid Disease

The challenge of eradicating leukemia in patients with acute myelogenous leukemia (AML) after initial cytoreduction has motivated modern efforts to combine synergistic active modalities including immunotherapy. Recently, the ETCTN/CTEP 10026 study tested the combination of the DNA methyltransferase inhibitor decitabine together with the immune checkpoint inhibitor ipilimumab for AML/myelodysplastic syndrome (MDS) either after allogeneic hematopoietic stem cell transplantation (HSCT) or in the HSCT-naïve setting. Integrative transcriptome-based analysis of 304 961 individual marrow-infiltrating cells for 18 of 48 subjects treated on study revealed the strong association of response with a high baseline ratio of T to AML cells. Clinical responses were predominantly driven by decitabine-induced cytoreduction. Evidence of immune activation was only apparent after ipilimumab exposure, which altered CD4+ T-cell gene expression, in line with ongoing T-cell differentiation and increased frequency of marrow-infiltrating regulatory T cells. For post-HSCT samples, relapse could be attributed to insufficient clearing of malignant clones in progenitor cell populations. In contrast to AML/MDS bone marrow, the transcriptomes of leukemia cutis samples from patients with durable remission after ipilimumab monotherapy showed evidence of increased infiltration with antigen-experienced resident memory T cells and higher expression of CTLA-4 and FOXP3. Altogether, activity of combined decitabine and ipilimumab is impacted by cellular expression states within the microenvironmental niche of leukemic cells. The inadequate elimination of leukemic progenitors mandates urgent development of novel approaches for targeting these cell populations to generate long-lasting responses. This trial was registered at www.clinicaltrials.gov as #NCT02890329

Return relationships among European equity sectors: a comparative analysis across selected sectors in small and large economies

This paper examines return interrelationships between numbers of equity sectors across several European markets. The markets comprise six Member States of the European Union (EU): namely, Belgium, Finland, France, Germany, Ireland and Italy. The five sectors include the consumer discretionary, consumer staples, financial, industrials and materials sectors. Generalised Autoregressive Conditional Heteroskedasticity in Mean (GARCH-M) models are used to consider the impact of returns in other European markets on the returns in each market across each sector. The results indicate that there are relatively few significant interrelationships between sectors in different markets, with most of these accounted for by the larger markets in France, Germany and Italy. The evidence also suggests the consumer discretionary, financial and materials sectors are relatively more interrelated than the consumer staples and industrials sectors. This has clear implications for portfolio diversification and asset pricing in the EU