Search

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic condition that affects up to 20% of premenopausal women. (1) It is multifactorial, with its etiology largely unknown. The syndrome is [...]

The placenta, composed of chorionic villi, changes dramatically across gestation. Understanding differences in ongoing pregnancies are essential to identify the role of chorionic villi at specific times in gestation and develop biomarkers and prognostic indicators of maternal–fetal health. The normative mRNA profile is established using next-generation sequencing of 124 first trimester and 43 third trimester human placentas from ongoing healthy pregnancies. Stably expressed genes (SEGs) not different between trimesters and with low variability are identified. Differential expression analysis of first versus third trimester adjusted for fetal sex is performed, followed by a subanalysis with 23 matched pregnancies to control for subject variability using the same genetic and environmental background. Placenta expresses 14,979 polyadenylated genes above sequencing noise (transcripts per million > 0.66), with 10.7% SEGs across gestation. Differentially expressed genes (DEGs) account for 86.7% of genes in the full cohort [false discovery rate (FDR) < 0.05]. Fold changes highly correlate between the full cohort and subanalysis (Pearson = 0.98). At stricter thresholds (FDR < 0.001, fold change > 1.5), there remains 50.1% DEGs (3353 upregulated in first and 4155 upregulated in third trimester). This is the largest mRNA atlas of healthy human placenta across gestation, controlling for genetic and environmental factors, demonstrating substantial changes from first to third trimester in chorionic villi. Specific differences and SEGs may be used to understand the specific role of the chorionic villi throughout gestation and develop first trimester biomarkers of placental health that transpire across gestation, which can be used for future development of biomarkers for maternal–fetal health.Comparison of first versus third trimester human placenta mRNA finds a subset of SEGs as well as significant changes in 86.7% of transcripts, highlighting the dynamic nature of placental function across gestation.Graphical Abstract

Mass spectrometry (MS) is a valuable tool for plasma proteome profiling and disease biomarker discovery. However, wide-ranging plasma protein concentrations, along with technical and biological variabilities, present significant challenges for deep and reproducible protein quantitation. Here, we evaluated the qualitative and quantitative performance of timsTOF HT and timsTOF Pro 2 mass spectrometers for analysis of neat plasma samples (unfractionated) and plasma samples processed using the Proteograph Product Suite (Proteograph) that enables robust deep proteomics sampling prior to mass spectrometry. Samples were evaluated across a wide range of peptide loading masses and liquid chromatography (LC) gradients. We observed up to a 76% increase in total plasma peptide precursors identified and a >2-fold boost in quantifiable plasma peptide precursors (CV < 20%) with timsTOF HT compared to Pro 2. Additionally, approximately 4.5 fold more plasma peptide precursors were detected by both timsTOF HT and timsTOF Pro 2 in the Proteograph analyzed plasma vs neat plasma. In an exploratory analysis of 20 late-stage lung cancer and 20 control plasma samples with the Proteograph, which were expected to exhibit distinct proteomes, an approximate 50% increase in total and statistically significant plasma peptide precursors (q< 0.05) was observed with timsTOF HT compared to Pro 2. Our data demonstrate the superior performance of timsTOF HT for identifying and quantifying differences between biologically diverse samples, allowing for improved disease biomarker discovery in large cohort studies. Moreover, researchers can leverage data sets from this study to optimize their liquid chromatography–mass spectrometry (LC–MS) workflows for plasma protein profiling and biomarker discovery. (ProteomeXchange identifier: PXD047854 and PXD047839).

To determine whether ovarian volume (OV) alone is an independent marker for metabolic dysfunction in women with suspected androgen excess.

Diffuse lung diseases are a heterogeneous group of disorders that can be difficult to differentiate by imaging using traditional methods of evaluation. The overlap between various disorders results in difficulty when medical professionals attempt to interpret images. Artificial intelligence offers new tools for the evaluation and quantification of imaging of patients with diffuse lung disease.

Background: Embryonic development may be compromised by dietary and genetic disruptions in folate metabolism because of the critical role of folate in homocysteine metabolism, methylation, and nucleotide synthesis. Methylenetetrahydrofolate reductase (MTHFR), choline, and riboflavin play distinct roles in homocysteine detoxification and generation of one-carbon donors for methylation. The effect of low dietary choline and riboflavin on pregnancy complications and heart development has not been adequately addressed. Objective: Our goal was to determine whether dietary deficiencies of choline and riboflavin in pregnant mice, with and without mild MTHFR deficiency, affect embryonic development. Design: Female [Mthfr.sup.+/+] and [Mthfr.sup.+/-] mice were fed a control diet (CD), a choline-deficient diet (ChDD), or a riboflavin-deficient diet (RbDD) and were then mated with male [Mthfr.sup.+/-] mice. Embryos were collected 14.5 d postcoitum and examined for reproductive outcomes and cardiac defects. Results: Plasma homocysteine was higher in ChDD- than in CD-fed females. Liver MTHFR enzyme activity was greater in ChDD-fed [Mthfr.sup.+/+] than in CD-fed [Mthfr.sup.+/+] females. The RbDD resulted in a higher percentage of delayed embryos and smaller embryos than did the CD. There were more heart defects, which were all ventricular septal defects, in embryos from the ChDD- and RbDD-fed females than from the CD-fed females. Dietary riboflavin and MTHFR deficiency resulted in decreased left ventricular wall thickness in embryonic hearts compared with embryos from CD-fed [Mthfr.sup.+/+] females. Conclusions: Low dietary choline and riboflavin affect embryonic growth and cardiac development in mice. Adequate choline and riboflavin may also play a role in the prevention of these pregnancy complications in women. Am J Clin Nutr 2010;91:1035-43. doi: 10.3945/ajcn.2009.28754.

This article traces the evolution of the screen kiss and the discourse surrounding it in Republican Shanghai leftwing cinema in the 1930s. The period from the 1910s to the 1930s in semi-colonial Shanghai witnessed an influx of Hollywood motion pictures that featured the screen kiss. By the 1930s, the circulation of images of Hollywood screen kiss in semi-colonial Shanghai triggered erotic imagination, comparison with Hollywood norms and most importantly the desire to appropriate, if not to reproduce, Hollywood screen kisses despite censorship. Two Shanghai leftist films, Street Angel(Malu tianshi, Yuan 1937) and Crossroads(Shizi jietou, Shen 1937), released shortly before the second Sino-Japanese War in 1937, appropriated and subverted Hollywood representational conventions of the screen kiss, fulfilling both the entertainment and pedagogical functions of cinema by constructing a sexually desiring and potentially class-conscious subject with aspirations for free love and social betterment at a critical moment of national crisis.1

Maternal and fetal pregnancy outcomes related to placental function vary based on fetal sex, which may be due to sexually dimorphic epigenetic regulation of RNA expression. We identified sexually dimorphic miRNA expression throughout gestation in human placentae. Next-generation sequencing identified miRNA expression profiles in first and third trimester uncomplicated pregnancies using tissue obtained at chorionic villous sampling (n= 113) and parturition (n= 47). Sequencing analysis identified 986 expressed mature miRNAs from female and male placentae at first and third trimester (baseMean>10). Of these, 11 sexually dimorphic (FDR < 0.05) miRNAs were identified in the first and 4 in the third trimester, all upregulated in females, including miR-361-5p, significant in both trimesters. Sex-specific analyses across gestation identified 677 differentially expressed (DE) miRNAs at FDR < 0.05 and baseMean>10, with 508 DE miRNAs in common between female-specific and male-specific analysis (269 upregulated in first trimester, 239 upregulated in third trimester). Of those, miR-4483 had the highest fold changes across gestation. There were 62.5% more female exclusive differences with fold change>2 across gestation than male exclusive (52 miRNAs vs 32 miRNAs), indicating miRNA expression across human gestation is sexually dimorphic. Pathway enrichment analysis identified significant pathways that were differentially regulated in first and third trimester as well as across gestation. This work provides the normative sex dimorphic miRNA atlas in first and third trimester, as well as the sex-independent and sex-specific placenta miRNA atlas across gestation, which may be used to identify biomarkers of placental function and direct functional studies investigating placental sex differences.Sex dimorphism in miRNA expression is more pronounced in first compared to third trimester placenta, and there are 62.5% more female exclusive gestational differences, indicating miRNA abundance across human gestation is also sexually dimorphic.

An efficient catalytic method to convert an α-C–H bond of N-alkylamines into an α-C–alkynyl bond was developed. In the past, such transformations were carried out under oxidative conditions, and the enantioselective variants were confined to tetrahydroisoquinoline derivatives. Here, we disclose a method for the union of N-alkylamines and trimethylsilyl alkynes, without the presence of an external oxidant and promoted through cooperative actions of two Lewis acids, B(C6F5)3and a Cu-based complex. A variety of propargylamines can be synthesized in high diastereo- and enantioselectivity. The utility of the approach is demonstrated by the late-stage site-selective modification of bioactive amines. Kinetic investigations that shed light on various mechanistic nuances of the catalytic process are presented.

Copyright of Vie Économique (Berne) is the property of State Secretariat for Economic Affairs (SECO) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An efficient deuteration process of β-amino C–H bonds in various N-alkylamine-based pharmaceutical compounds has been developed. Catalytic reactions begin with the action of Lewis acidic B(C6F5)3and Brønsted basic N-alkylamine, converting a drug molecule into the corresponding enamine. The acid/base catalysts also promote the dedeuteration of acetone-d6to afford a deuterated ammonium ion. Ensuing deuteration of the enamine then leads to the formation of β-deuterated bioactive amines with up to 99% deuterium incorporation.

Infertility affects 10% of the reproductive-age population. Even the most successful treatments such as assisted reproductive technologies still result in failed implantation. In addition, adverse pregnancy outcomes associated with infertility have been attributed to these fertility treatments owing to the presumed epigenetic modifications of in vitro fertilization and in vitro embryo development. However, the diagnosis of infertility has been associated with adverse outcomes, and the etiologies leading to infertility have been associated with adverse pregnancy and long-term outcomes.

No studies have examined the fertility priorities of women undergoing treatment for their glioma. Glioma patients frequently undergo chemotherapy as part of their treatment; however, it is unknown whether patients truly are aware of its possible effects on their fertility. Our objective was to assess the fertility priorities of glioma patients and ascertain whether female glioma patients are being effectively counseled on the effects of chemotherapy on their fertility prior to beginning treatment.

Maternal metabolic status reflects underlying physiological changes in the maternal-placental-fetal unit that may help identify contributors to adverse pregnancy outcomes associated with infertility and treatments used.

An efficient method for the coupling of N-alkylamines with silicon enolates to generate β-amino carbonyl compounds is disclosed. These reactions proceed by activation of α-amino C–H bonds by B(C6F5)3, which likely generates a “frustrated” acid/base complex in the presence of large N-alkylamines. The transformation requires no external oxidant and releases hydrosilane as a byproduct. The utility of this method is demonstrated in the late-stage functionalization of bioactive molecules such as citalopram, atomoxetine, and fluoxetine.

Catalytic transformations of α-amino C–H bonds to afford valuable enantiomerically enriched α-substituted amines, entities that are prevalent in pharmaceuticals and bioactive natural products, have been developed. Typically, such processes are carried out under oxidative conditions and require precious metal-based catalysts. Here, we disclose a strategy for an enantioselective union of N-alkylamines and α,β-unsaturated compounds, performed under redox-neutral conditions, and promoted through concerted action of seemingly competitive Lewis acids, B(C6F5)3, and a chiral Mg–PyBOX complex. Thus, a wide variety of β-amino carbonyl compounds may be synthesized, with complete atom economy, through stereoselective reaction of an in situ-generated enantiomerically enriched Mg-enolate and an appropriate electrophile.

EDITOR'S SUMMARY 3D printing enables physical objects to be constructed from a virtual 3D model with the aid of a computer-aided design (CAD) program. The CAD files and printed physical product may be protected by copyright law, covering rights to reproduce and distribute copies of the work, make derivative works and publicly display or perform the work. Copyright does not cover useful articles or works in the public domain. Libraries could become entangled in copyright infringement directly or secondarily by providing the equipment that may be used to infringe on a copyright. Libraries can manage their risks by developing and implementing policies regarding 3D printer use, including using a mediated service model and being mindful of the 'unsupervised copying' exception in the copyright law for libraries and archives. Patron education on 3D printing provides an opportunity to explain library policies on use and copyright issues. [ABSTRACT FROM AUTHOR]

AbstractIn his formalist reading, David Bordwell (2001: 73, 80) uses the term ‘pause-burst-pause’ pattern to refer to the ‘cinematic expressivity’ of Hong Kong action cinema. Although the ‘pause-burst-pause’ paradigm locates stasis and action that lie at the heart of the performance and cinematic representation of physical action, the ‘pause-burst-pause’ punctuation undergoes aesthetic transformation in the digital age. Through a comparative analysis of five representative films from the 1960s to the millennium, this article explores Hong Kong action cinema’s historical evolution from the display of physical combat (swordplay, kung fu and gunplay) to intense psychological mind game and heightened aestheticization in four stylistic turns – fantastic, realist, formalist and digital. Wong Kar-wai’s Yi dai zong shi/The Grandmaster (2013), following the box office success of transnational Chinese martial arts cinemas, serves as a prime example of the digital turn as postcolonial Hong Kong action cinema positions and articulates itself to an increasingly international film scene. Taking Lisa Purse’s (2005: 152) notion of ‘hypermediacy’ as a springboard, I argue that the combined use of computer-generated imagery (CGI) and aestheticized slow motion in The Grandmaster represents a new appreciation of slowness and softness, reinventing corporeal authenticity that the action genre is premised on.

Acinetobacterhas low virulence but causes infections in subjects with reduced immunity. It has been reported in ocular infections including those of patients using contact lenses. Treatment is difficult because Acinetobacteris frequently multidrug resistant. Antibiotic-resistant strains frequently also harbor genes for antiseptic resistance (quaternary ammonium compound QAC) genes. Because Acinetobacteris part of the normal flora, it may contaminate contact lens and accessories. This study aims to investigate carriage rates of QAC genes in household and clinical isolates of Acinetobacterand to determine the effectiveness of two multipurpose solutions (MPSs) for soft lenses against organisms carrying QAC genes.

AbstractAtherosclerosis is a disease characterized by excess cholesterol and inflammation in the blood vessels. The liver X receptors (á and â) are members of the nuclear hormone receptor family that are activated by endogenous cholesterol metabolites. These receptors are widely expressed with a tissue distribution that includes the liver, intestine and macrophage. Upon activation, these receptors have been shown to increase reverse cholesterol transport from the macrophage back to the liver to aid in the removal of excess cholesterol. More recently, they have also been shown to inhibit the inflammatory response in macrophages. These functions are accomplished through direct regulation of gene transcription. Herein, we will describe the key benefits and potential risks of targeting the liver X receptors for the treatment of atherosclerosis.

Neoplastic T cells in mycosis fungoides (MF) are resistant to apoptotic agents, including galectin-1 that is abundant in skin. Although MF cells are typically CD7–, and thus galectin-1 resistant, CD7+HH cells, derived from a patient with MF, were also resistant to galectin-1. HH cells demonstrate altered cell surface glycosylation, with loss of core 2 O-glycan ligands for galectin-1 created by core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT-I). Loss of core 2 O-glycans on tumor cells was also seen in primary CD7+MF lesions. Surprisingly, HH cells are heterozygous for a C2GnT-I point mutation, yet this mutation resulted in a dramatic reduction in cellular glycosyltransferase activity. Expression of wild-type C2GnT-I in human HH cells, or murine lymphoma cells that lack C2GnT-I, restored core 2 O-glycan expression and susceptibility to galectin-1, whereas mutant enzyme lacked activity and did not restore core 2 O-glycan expression or susceptibility to galectin-1. Mutant enzyme did not have a dominant negative effect by affecting dimerization or activity of wild-type enzyme; rather, C2GnT-I haploinsufficiency is sufficient for loss of core 2 O-glycan expression and galectin-1 resistance. Thus, glycosyltransferase haploinsufficiency results in altered cellular glycosylation and resistance to cell death, identifying a new survival mechanism for T-lymphoma cells.

This study describes the development and implementation of a large-scale primary fall and fracture prevention programme in Hong Kong and its effect on increasing the awareness and knowledge of fall and fracture prevention among older people. The effect of promotion of community participation is also investigated in the implementation of this primary prevention programme. The programme includes educational seminars, a train-the-trainers programme and a staff training programme. The effect of the educational seminars is shown by the increase in the knowledge and awareness of fall and fracture prevention among these participants (p<0.01), while that of the train-the-trainers programme and staff-training programme is confirmed by the continuous expansion and continuation of the fall and fracture prevention programme in the community. The experience from this primary prevention programme has given us direction for future implementation of a more comprehensive prevention programme in our community.

Background:Follicular lymphoma (FL) is the most common indolent non-Hodgkin's lymphoma, with 8% of patients presenting with stage II disease. Stage II FL is potentially curable with radiation therapy (RT), but more than half of patients relapse within 10 years. The Ann Arbor stage II definition encompasses a broad spectrum of disease extents and distributions; understanding how these factors affect outcomes could enable identification of patients at higher risk for progression. The purpose of this study was to investigate the impact of disease extent and distribution on outcomes in stage II FL.

Features the top ten best cities in Asia, according to `Asiaweek' magazine. Tokyo, Japan; Singapore; Bandar Seri Begawan, Brunei; Osaka, Japan; Sendai, Japan; Hong Kong; Kuala Lumpur, Malaysia; Cebu, Philippines; Chiang Mai, Thailand; Georgetown, Malaysia.