Association of Mosaic Chromosomal Alterations and Genetic Factors with the Risk of Cirrhosis.

Background and Aims: Age-related mosaic chromosomal alterations (mCAs) detected from genotyping of blood-derived DNA are structural somatic variants that indicate clonal hematopoiesis. This study aimed to investigate whether mCAs contribute to the risk of cirrhosis and modify the effect of a polygenic risk score (PRS) on cirrhosis risk prediction. Methods: mCA call sets of individuals with European ancestry were obtained from the UK Biobank. The PRS was constructed based on 12 susceptible single-nucleotide polymorphisms for cirrhosis. Cox proportional hazard models were applied to evaluate the associations between mCAs and cirrhosis risk. Results: Among 448,645 individuals with a median follow-up of 12.5 years, we identified 2,681 cases of cirrhosis, 1,775 cases of compensated cirrhosis, and 1,706 cases of decompensated cirrhosis. Compared to non-carriers, individuals with copy-neutral loss of heterozygosity mCAs had a significantly increased risk of cirrhosis (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.12-1.81). This risk was higher in patients with expanded cell fractions of mCAs (cell fractions ≥10% vs. cell fractions <10%), especially for the risk of decompensated cirrhosis (HR 2.03 [95% CI 1.09-3.78] vs. 1.14 [0.80-1.64]). In comparison to non-carriers of mCAs with low genetic risk, individuals with expanded copy-neutral loss of heterozygosity and high genetic risk showed the highest cirrhosis risk (HR 5.39 [95% CI 2.41-12.07]). Conclusions: The presence of mCAs is associated with increased susceptibility to cirrhosis risk and could be combined with PRS for personalized cirrhosis risk stratification.

Association between concentrations of rare earth elements in chorionic villus and risk for unexplained spontaneous abortion.

Rare earth elements (REEs) exposure during pregnancy may increase the risk of unexplained spontaneous abortion. However, the association between REEs intrauterine exposure and unexplained spontaneous abortion had yet to be studied. In order to conduct this large case-control study, we thus collected chorionic villus from 641 unexplained spontaneous abortion and 299 control pregnant women and detected the concentrations of 15 REEs by inductively coupled plasma mass spectrometer (ICP-MS). Because the detection rates of 10 REEs were less than 80%, the remaining 5 REEs, which were lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd) and yttrium (Y), underwent to further analysis. The association between 5 REEs and unexplained spontaneous abortion was assessed by using the logistic regression, bayesian kernel regression (BKMR) and weighted quantile sum regression (WQS) models. In the adjusted logistic regression model, Pr, Nd and Y enhanced the incidence of unexplained spontaneous abortion in a dose-dependent way and Ce increased the risk only at high concentration group. The result of BKMR model demonstrated that the risk of unexplained spontaneous abortion increased as the percentile of five mixed REEs increased. Y and Nd were both significantly associated with an increased incidence of unexplained spontaneous abortion, but La was correlated with a decrease in the risk of unexplained spontaneous abortion. Pr was substantially associated with an increase in the risk of unexplained spontaneous abortion when other REEs concentrations were fixed at the 25th and 50th percentiles. According to WQS regression analysis, the WQS index was significantly associated with unexplained spontaneous abortion (OR = 3.75, 95% CI:2.40-5.86). Y had the highest weight, followed by Nd and Pr, which was consistent with the analysis results of our other two models. In short, intrauterine exposure to REEs was associated with an increased risk of unexplained spontaneous abortion, with Y, Nd and Pr perhaps playing an essential role.

Association between exposure to per- and polyfluoroalkyl substance and liver injury in American adults.

Epidemiological data is scarce regarding the association between exposure to mixtures of per- and polyfluoroalkyl substances (PFASs) and liver injury in the general populace. The current research used data from the National Health and Nutrition Examination Survey (2009-2018). The PFAS exposure levels were defined by the serum concentrations of PFASs with > 70% detection in samples, namely perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDeA), and perfluorooctane sulfonic acid (PFOS). Liver injury was assessed from two aspects: first, the degree of liver inflammation was determined based on serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyltransferase (GGT), and total bilirubin (TBIL) levels; second, the degree of liver fibrosis was determined based on fibrosis-4 (FIB-4) index. We assessed the associations between individual or total PFAS exposure and these outcomes using multivariable linear regression models and logistic regression models, restricted cubic splines, and weighted quantile sum regression. Among the samples of 7484 American adults, the median concentration of PFOS was the highest, followed by PFOA and PFHxS. Using multivariable linear regression, a positive correlation was observed between all PFASs and liver enzymes such as ALT, AST, and TBIL. Additionally, the weighted quantile sum model indicated an overall positive association between the five PFASs and liver injury indicators. For liver function biomarkers and liver fibrosis, PFNA and PFOS were the most heavily weighting chemicals, respectively. Our findings provide new epidemiological evidence indicating a potential association between PFAS exposure and adverse effects on liver injury biomarkers, highlighting the potentially harmful effects of PFAS exposure on liver health.

Low follistatin level is a causal risk factor for spontaneous abortion: a two-sample mendelian randomization study.

Background: Recurrent pregnancy loss is a distressing event during pregnancy, and understanding its causal factors is crucial. Follistatin, a glycoprotein involved in folliculogenesis and embryogenesis, has been implicated as a potential contributor to the risk of spontaneous abortion. However, establishing a causal relationship requires rigorous investigation using robust methods. Methods: In this study, we utilized mendelian randomization (MR), a powerful genetic epidemiological approach, to examine the causal relationship between follistatin levels and spontaneous abortion. We obtained instrumental variables strongly associated with follistatin levels from large-scale genome-wide association from the IEU database. The inverse variance weighting (IVW) method was taken as gold standard. We also performed sensitivity test to evaluate the robustness of our result. Results: MR analysis revealed a significant causal relationship between low follistatin levels and spontaneous abortion (p = 0.03). Sensitivity analyses, including pleiotropy test, heterogeneity test, and leave-one-out analysis, all supported the robustness of our findings. Conclusion: Our study provides compelling evidence supporting the causal relationship between low follistatin levels and increased risk of spontaneous abortion. These findings underscore the importance of follistatin in the etiology of spontaneous abortion and suggest potential preventive interventions. Modulating follistatin levels or relevant pathways could hold promise for reducing the incidence of spontaneous abortion and improving reproductive outcomes. The utilization of MRs strengthens the validity of our results by mitigating confounding and reverse causality biases. Further research is needed to elucidate the underlying molecular mechanisms and explore therapeutic strategies targeting follistatin levels.

PNGase H + variant from Rudaea cellulosilytica with improved deglycosylation efficiency for rapid analysis of eukaryotic N-glycans and hydrogen deuterium exchange mass spectrometry analysis of glycoproteins.

The analysis of glycoproteins and the comparison of protein N-glycosylation from different eukaryotic origins require unbiased and robust analytical workflows. The structural and functional analysis of vertebrate protein N-glycosylation currently depends extensively on bacterial peptide-N4-(N-acetyl-ß-glucosaminyl) asparagine amidases (PNGases), which are indispensable enzymatic tools in releasing asparagine-linked oligosaccharides (N-glycans) from glycoproteins. So far, only limited PNGase candidates are available for N-glycans analysis, and particularly the analysis of plant and invertebrate N-glycans is hampered by the lack of suitable PNGases. Furthermore, liquid chromatography-mass spectrometry (LC-MS) workflows, such as hydrogen deuterium exchange mass spectrometry (HDX-MS), require a highly efficient enzymatic release of N-glycans at low pH values to facilitate the comprehensive structural analysis of glycoproteins. Herein, we describe a previously unstudied superacidic bacterial N-glycanase (PNGase H+ ) originating from the soil bacterium Rudaea cellulosilytica (Rc), which has significantly improved enzymatic properties compared to previously described PNGase H+ variants. Active and soluble recombinant PNGase Rc was expressed at a higher protein level (3.8-fold) and with higher specific activity (~56% increase) compared to the currently used PNGase H+ variant from Dyella japonicum (Dj). Recombinant PNGase Rc was able to deglycosylate the glycoproteins horseradish peroxidase and bovine lactoferrin significantly faster than PNGase Dj (10 min vs. 6 h). The versatility of PNGase Rc was demonstrated by releasing N-glycans from a diverse array of samples such as peach fruit, king trumpet mushroom, mouse serum, and the soil nematode Caenorhabditis elegans. The presence of only two disulfide bonds shown in the AlphaFold protein model (so far all other superacidic PNGases possess more disulfide bonds) could be corroborated by intact mass- and peptide mapping analysis and provides a possible explanation for the improved recombinant expression yield of PNGase Rc.

Correction: Fast label-free recognition of NRBCs by deep-learning visual object detection and single-cell Raman spectroscopy.

Correction for 'Fast label-free recognition of NRBCs by deep-learning visual object detection and single-cell Raman spectroscopy' by Teng Fang et al., Analyst, 2022, https://doi.org/10.1039/D2AN00024E.

Fast label-free recognition of NRBCs by deep-learning visual object detection and single-cell Raman spectroscopy.

Nucleated red blood cells (NRBCs) as a type of rare cell present in an adult's peripheral blood is a concern in hematology, intensive care medicine and prenatal diagnostics. However, it is labor-intensive to screen such rare cells from real complex cell mixtures especially in a label-free way. Herein, we report a new label-free method that incorporates image recognition and Raman spectroscopy for fast recognition of the rare cells in blood. First, we identified unlabeled NRBCs based on both Raman signals of hemoglobin and nucleated morphology, and recorded their microscopic image characteristics which were different enough from other blood cells in unlabeled morphology. Then, two deep-learning algorithms of visual object detection, Faster RCNN and YOLOv3, were investigated for cell morphological recognition on a low-cost computer configuration, and YOLOv3 was demonstrated to be more competent for real-time detection despite slightly lower precision. Finally, several NRBCs were successfully found in maternal blood using this method, which verified the methodological feasibility. Thus, we believe such a labor-saving approach might inspire a new idea for detecting rare cells from complex cell mixtures in a label-free and computer-assisted way.

Single-copy Loss of Rho Guanine Nucleotide Exchange Factor 10 ( arhgef10) Causes Locomotor Abnormalities in Zebrafish Larvae.

OBJECTIVE: To determine if ARHGEF10 has a haploinsufficient effect and provide evidence to evaluate the severity, if any, during prenatal consultation. METHODS: Zebrafish was used as a model for generating mutant. The pattern of arhgef10 expression in the early stages of zebrafish development was observed using whole-mount in situ hybridization (WISH). CRISPR/Cas9 was applied to generate a zebrafish model with a single-copy or homozygous arhgef10 deletion. Activity and light/dark tests were performed in arhgef10 -/-, arhgef10 +/-, and wild-type zebrafish larvae. ARHGEF10 was knocked down using small interferon RNA (siRNA) in the SH-SY5Y cell line, and cell proliferation and apoptosis were determined using the CCK-8 assay and Annexin V/PI staining, respectively. RESULTS: WISH showed that during zebrafish embryonic development arhgef10 was expressed in the midbrain and hindbrain at 36-72 h post-fertilization (hpf) and in the hemopoietic system at 36-48 hpf. The zebrafish larvae with single-copy and homozygous arhgef10 deletions had lower exercise capacity and poorer responses to environmental changes compared to wild-type zebrafish larvae. Moreover, arhgef10 -/- zebrafish had more severe symptoms than arhgef10 +/- zebrafish. Knockdown of ARHGEF10 in human neuroblastoma cells led to decreased cell proliferation and increased cell apoptosis. CONCLUSION: Based on our findings, ARHGEF10 appeared to have a haploinsufficiency effect.

SP1-Mediated Upregulation of Long Noncoding RNA ZFAS1 Involved in Non-syndromic Cleft Lip and Palate via Inactivating WNT/ß-Catenin Signaling Pathway.

Non-syndromic cleft lip and palate (NSCLP) is one of the most common congenital malformations with multifactorial etiology. Although long non-coding RNAs (lncRNAs) have been implicated in the development of lip and palate, their roles in NSCLP are not fully elucidated. This study aimed to investigate how dysregulated lncRNAs contribute to NSCLP. Using lncRNA sequencing, bioinformatics analysis, and clinical tissue sample detection, we identified that lncRNA ZFAS1 was significantly upregulated in NSCLP. The upregulation of ZFAS1 mediated by SP1 transcription factor (SP1) inhibited expression levels of Wnt family member 4 (WNT4) through the binding with CCCTC-binding factor (CTCF), subsequently inactivating the WNT/ß-catenin signaling pathway, which has been reported to play a significant role on the development of lip and palate. Moreover, in vitro, the overexpression of ZFAS1 inhibited cell proliferation and migration in human oral keratinocytes and human umbilical cord mesenchymal stem cells (HUC-MSCs) and also repressed chondrogenic differentiation of HUC-MSCs. In vivo, ZFAS1 suppressed cell proliferation and numbers of chondrocyte in the zebrafish ethmoid plate. In summary, these results indicated that ZFAS1 may be involved in NSCLP by affecting cell proliferation, migration, and chondrogenic differentiation through inactivating the WNT/ß-catenin signaling pathway.

[Genetic analysis of an individual with a fragile site at 16q22].

OBJECTIVE: To analyze a patient with infertility and a fragile site found at 16q22 by using cytogenetic methods. METHODS: Peripheral blood sample was taken from the patient and subjected to chromosomal karyotyping and single nucleotide polymorphism microarray (SNP-array) analysis. RESULTS: The patient was found to be a mosaicism for a fragile site at 16q22, which has a variable morphology and cannot be induced by folic acid treatment. No abnormality was found by SNP-array analysis. CONCLUSION: A rare fragile site, which can be induced without folic acid treatment, has been identified at 16q22. The strategy of assisted reproduction for such individuals is yet to be explored.

Aberration of Serum and Tissue N-Glycans in Mouse ß1,4-GalT1 Y286L Mutant Variants.

ß1,4-GalT1 is a type II membrane glycosyltransferase. It catalyzes the production of lactose in the lactating mammary gland and is supposedly also involved in the galactosylation of terminal GlcNAc of complex-type N-glycans. In-vitro studies of the bovine ß4Gal-T1 homolog showed that replacing a single residue of tyrosine with leucine at position 289 alters the donor substrate specificity from UDP-Gal to UDP-N-acetyl-galactosamine (UDP-GalNAc). The effect of this peculiar change in ß1,4GalT1 specificity was investigated in-vivo, by generating biallelic Tyr286Leu ß1,4GalT1 mice using CRISPR/Cas9 and crossbreeding. Mice bearing this mutation showed no appreciable defects when compared to wild-type mice, with the exception of biallelic female B4GALT1 mutant mice, which were unable to produce milk. The detailed comparison of wild-type and mutant mice derived from liver, kidney, spleen, and intestinal tissues showed only small differences in their N-glycan pattern. Comparable N-glycosylation was also observed in HEK 293 wild-type and knock-out B4GALT1 cells. Remarkably and in contrast to the other analyzed tissue samples, sialylation and galactosylation of serum N-glycans of biallelic Tyr286Leu GalT1 mice almost disappeared completely. These results suggest that ß1,4GalT1 plays a special role in the synthesis of serum N-glycans. The herein described Tyr286Leu ß1,4GalT1 mutant mouse model may, therefore, prove useful in the investigation of the mechanism which regulates tissue-dependent galactosylation.

DeepACEv2: Automated Chromosome Enumeration in Metaphase Cell Images Using Deep Convolutional Neural Networks.

Chromosome enumeration is an essential but tedious procedure in karyotyping analysis. To automate the enumeration process, we develop a chromosome enumeration framework, DeepACEv2, based on the region based object detection scheme. The framework is developed following three steps. Firstly, we take the classical ResNet-101 as the backbone and attach the Feature Pyramid Network (FPN) to the backbone. The FPN takes full advantage of the multiple level features, and we only output the level of feature map that most of the chromosomes are assigned to. Secondly, we enhance the region proposal network's ability by adding a newly proposed Hard Negative Anchors Sampling to extract unapparent but essential information about highly confusing partial chromosomes. Next, to alleviate serious occlusion problems, besides the traditional detection branch, we novelly introduce an isolated Template Module branch to extract unique embeddings of each proposal by utilizing the chromosome's geometric information. The embeddings are further incorporated into the No Maximum Suppression (NMS) procedure to improve the detection of overlapping chromosomes. Finally, we design a Truncated Normalized Repulsion Loss and add it to the loss function to avoid inaccurate localization caused by occlusion. In the newly collected 1375 metaphase images that came from a clinical laboratory, a series of ablation studies validate the effectiveness of each proposed module. Combining them, the proposed DeepACEv2 outperforms all the previous methods, yielding the Whole Correct Ratio(WCR)(%) with respect to images as 71.39, and the Average Error Ratio(AER)(%) with respect to chromosomes as about 1.17.

Identification of a 6-month-old baby with a combination of WAGR and Potocki-Shaffer contiguous deletion syndromes by SNP array testing.

WAGR 11p13 deletion syndrome is associated with abnormalities including (W) ilms tumor, (A) niridia, (G) enitourinary abnormalities, and growth and mental (R) etardation (WAGR). Potocki-Schaffer syndrome is a contiguous gene syndrome associated with deletions in 11p11.2, principal features of which are multiple exostoses, parietal foramina development delay, mental retardation, and facial dysmorphism. In some cases, males may have enlarged anterior fontanels and genital abnormalities. Each of these syndromes is very rare. Here we report a patient with both WAGR and Potocki-Shaffer syndromes who presented with aniridia, nystagmus, macular dysplasia, enlarged anterior fontanel, mental retardation, ptosis, low-set ears, micrognathia, and atrial septal defect at 6 months old. SNP array revealed a large (26.25 Mb)deletion: arr[hg19]11p15.1p11.2(18742043-44991839)× 1. Genetic testing allowed for diagnosis of this patient at a very young age. In addition to the postnatal phenotype of the patient, we found one prenatal symptom of these syndromes is oligohydramnios, which when present might indicate advanced prenatal diagnosis. This made the possibility of prenatal diagnosis for these syndromes.

Effects of tenuifolin on rest/wake behaviour in zebrafish.

Insomnia is a common sleep disorder with a high prevalence and substantial adverse consequences. There is growing interest in identifying novel therapeutics from herbal medicine. Tenuifolin is a major constituent of the well-known anti-insomnia herb Radix Polygala. The present study investigated the neural activity in response to tenuifolin during rest/wake behaviour in zebrafish and identified the potential biological signalling pathways involved. An automatic video tracking system was used to monitor the behavioural response of zebrafish larvae for 24 h after treatment with tenuifolin. In total, six rest/wake parameters were measured and visualized with a behavioural fingerprint. Time series analysis was conducted by averaging the total rest and waking activity in 10 min intervals. A correlation analysis was performed between tenuifolin and well-known compounds to analyse the underlying biological signalling pathways. Reverse transcription-quantitative PCR was also performed to detect the effects of tenuifolin on the transcription of interesting genes associated with the signalling pathways that were potentially involved. The present results suggested tenuifolin significantly increased the total rest time during the dark phase, with a slight effect on the waking activity in zebrafish larvae. This behavioural phenotype induced by tenuifolin is similar to that of selective serotonin reuptake inhibitors and gamma-aminobutyric acid (GABA) agonists. Furthermore, the expression levels of GABA transporter 1 were significantly increased after tenuifolin treatment. No significant difference was determined in other associated genes in untreated control and tenuifolin-treated larvae. The present results suggested that tenuifolin caused sleep-promoting activity in zebrafish and that these effects may be mediated by the serotoninergic systems and the GABAergic systems.

Evidence of compliance with and effectiveness of guidelines for noninvasive prenatal testing in China: a retrospective study of 189,809 cases.

In China, the medical guidelines recommend performing noninvasive prenatal testing (NIPT) with caution for pregnant women aged 35 years or older. However, the Mother and Child Health Care Law suggests that all primiparous women whose age is older than 35 years undergo prenatal diagnosis. These two inconsistent suggestions/recommendations have made obstetricians confused about whether to offer NIPT to these older pregnant women. To face this issue and find out the solution we performed a retrospective study of 189,809 NIPT samples collected from 28 provincial-leveled administrative units in China. Of 1,564 women with high-risk pregnancies who underwent NIPT, 459 (29.3%) did not participate in follow-up. The compound sensitivity and specificity of NIPT for trisomies 21, 18 and 13 detection was 99.1% (95% CI, 98.0%-99.6%) and 99.9% (95% CI, 98.8%-99.9%), respectively. In secundiparous women, NIPT showed high sensitivity and specificity similar to that in primiparous women. The observed risk for trisomies 21 and 18 significantly increased when the maternal age was 39 and older. After the publication of the current NIPT policy, the follow-up rate at our center was 91.9%; however, a large number of women are not in maternal and infant care networks nationwide, and that makes the follow-up rate outside our center relatively low. Our study shows that to balance the prevention of major aneuploidies and the limited resources for prenatal diagnosis, the cut-off age of 35 for invasive prenatal diagnosis might be unnecessary. Although the NIPT guidelines are well written, how to practice it effectively, especially in less industrialized areas, is worth discussing.

Guidelines for the management of atopic dermatitis: A literature review and consensus statement of the Philippine Dermatological Society

@#Introduction: Atopic dermatitis (AD) is a complex disease with an interplay of genetic and environmental factors. In the United States, AD affects 10.7% of children andyc 7.2% of adults. Similarly in the Philippines, the prevalence of AD is 12.7% in the under 18 population, and 2% in the over 18 population. While AD affects all ages, the burden of the disease is greater in the pediatric population. The pathogenesis of AD is multifactorial. Variations in genes responsible for epidermal barrier function, keratinocyte terminal differentiation, and the innate and adaptive immune responses have been linked to AD. A null mutation involving the filaggrin gene is the strongest known risk factor for AD. This mutation results in a loss of filaggrin (FLG) protein by at least 50%. Filaggrin breakdown products form part of the natural moisturizing factor (NMF) of the skin, which is essential in skin hydration. A decrease in NMF and an increase in transepidermal water loss (TEWL) are observed in AD patients with FLG mutation. The defective barrier in AD patients decreases skin defenses against irritation and allergen penetration. Exposure to certain environmental chemicals like formaldehyde may worsen this barrier. This may lead to increased skin permeability to aeroallergens that leads to dermatitis in sensitized patients. Barrier defects may also play a role in epicutaneous sensitization and the subsequent development of other atopic conditions, such as bronchial asthma and allergic rhinitis. The Philippine Dermatological Society (PDS) consensus on AD aims to provide a comprehensive guideline and evidence-based recommendations in the management of this condition, with consideration of cultural factors that are often encountered in the Philippine setting. These guidelines are intended to provide practitioners with an overview of the holistic approach in the management of AD, ameliorating the negative effects of the disease and improving overall quality of life.. Methodology: A group of 21 board-certified dermatologists from the Philippine Dermatological Society (PDS) convened to discuss aspects in the clinical management of AD. Database and literature search included the full-text articles of observational studies, randomized controlled clinical trials, and observational studies using the Cochrane library, PubMed, Hardin (for Philippine based studies) as well as data from the PDS health information system. The terms used in combinations from the literature included “atopic dermatitis”, “atopic eczema”, “emollients”, “topical corticosteroids”, “topical calcineurin inhibitors”, “anti-histamines” and “phototherapy”. A total of fifty (50) full text articles were reviewed and found applicable for the scope of the study. Articles were assessed using the modified Jadad scale, with score interpretations as follows: (5- excellent, 3- good, 1– poor). Consensus guidelines for AD from within and outside of the region were also reviewed, from the 2013 Asia-Pacific guidelines, 2014 Taiwanese Dermatological Association consensus, 2016 guidelines in the management of AD in Singapore, 2014 American Academy of Dermatology guidelines, and the 2020 Japanese guidelines for AD. From the literature review, proposed consensus statements were developed, and a Delphi survey was conducted over two separate virtual meetings. Individual dermatologists provided Likert Scoring (1- strongly disagree to 5- strongly agree) based on consensus statements. A consensus was deemed reached at mean scores of > 4.00, a near consensus at > 3.5, and no consensus at <3.5. Summary: AD is a chronic relapsing condition with a significant burden of disease, most commonly affecting the pediatric population. The PDS AD Consensus Guidelines summarizes the standards of therapy and the therapeutic ladder in the management of AD based on published clinical trials and literature review. While these modalities remain the cornerstone of therapy, an individualized approach is the key to the holistic management of an AD patient. Knowledge and awareness of frequently associated conditions, whether in the realm of food allergies, contact allergies, or secondary infections, is paramount. In addition to the standard therapeutic armamentarium, the physician must also consider cultural practices and be knowledgeable of alternative therapeutic options. Referral to a specialist is recommended for recalcitrant cases of AD, or when initiation of systemic immunosuppressive agents, phototherapy, or biologic agents is contemplated.

A case report and mechanism analysis of a normal phenotype mosaic 47, XXY complicated by paternal iUPD (9) who had a normal PGD result.

BACKGROUND: Uniparental disomy (UPD) refers to the situation in which two copies of homologous chromosomes or part of a chromosome originate from the one parent and no copy is supplied by the other parent. CASE PRESENTATION: Here, we reported a woman whose karyotype was 46, XX, t (1;17)(q42;q21), has obtained 5 embryos by intracytoplasmic sperm injection (ICSI) after one cycle of in vitro fertility (IVF). After microarray-based comparative genomic hybridization (array-CGH) for preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR), two embryos were balanced, one balanced embryo was implanted and the patient successfully achieved pregnancy. Amniocentesis was performed at the 19th week of gestation for karyotype analysis and single nucleotide polymorphism (SNP)-array test. The result of karyotype analysis was: mos 47, XXY [19]/46, XY [81]; SNP-array results revealed 46, XY, iUPD (9) pat. After full genetic counseling for mosaic Klinefelter's syndrome and paternal iUPD (9), the couple decided to continue pregnancy, and the patient gave birth to a healthy boy. The newborn is now 3.5 years old, and developed normally. This case will provide counseling evidences of paternal iUPD (9) for doctors. CONCLUSIONS: This is the first case report of paternal iUPD9 with mosaic Klinefelter's syndrome, and no abnormality has been observed during the 3.5-year follow-up. Further observation is required to determine whether the imprinted genes on the chromosomes are pathogenic and whether recessive pathogenetic genes are activated.

ULK1 phosphorylates Mad1 to regulate spindle assembly checkpoint.

The spindle assembly checkpoint (SAC) ensures the fidelity of chromosome segregation during mitosis. Here, we show that ULK1, a serine/threonine kinase that plays a key role in initiation of autophagy, also has an important function in the activation of SAC. ULK1 phosphorylates the SAC protein Mad1 at Ser546 to recruit Mad1 to kinetochores. Furthermore, Rod/ZW10/Zwilch (RZZ) complex may serve as a receptor for phos-Ser546-Mad1 at kinetochore, since phosphorylation of Mad1 by ULK1 strengthens the interaction between Mad1 and RZZ complex. In addition, deletion of ULK1 increases chromosome instability and cytotoxicity of paclitaxel, resulting in significant impairment of cancer cell growth. These findings highlight the role of ULK1 as a protein kinase controlling the fidelity of chromosome segregation and cell-cycle progression.

Using polyethylene plastic bag to prevent moderate hypothermia during transport in very low birth weight infants: a randomized trial.

OBJECTIVE: Hypothermia remains a significant problem among very low birth weight (VLBW) infants. The use of occlusive polyethylene plastic bags immediately after birth has been proven to be effective for preterm infants to reduce hypothermia. This study aims to determine whether placing VLBW infants in plastic bags during transport reduces hypothermia. STUDY DESIGN: Study infants were randomly assigned to a standard thermoregulation protocol or to a standard thermoregulation protocol with placement of the torso and lower extremities inside a polyethylene plastic bag during transport. The primary outcome measures were axillary temperature before and after transport and the occurrence of moderate hypothermia upon neonatal intensive care unit admission. RESULT: The 108 VLBW infants recruited into the study were randomized to the plastic bag (n = 54) group or to standard group (n = 54) and had similar baseline characteristics. VLBW infants in the plastic bag group had a lower rate of moderate hypothermia (3.7 vs 27.8%; risk ratio 0.10; confidence interval 0.02-0.46; P < 0.001) and higher axillary temperatures (36.4 ± 0.4 °C vs 35.9 ± 0.9 °C; P = 0.001) upon NICU admission compared to infants receiving standard care. CONCLUSION: Placing VLBW infants in polyethylene plastic bags during transport reduces the occurrence of hypothermia, especially moderate hypothermia.

A de novo complex chromosome rearrangement associated with multisystematic abnormalities, a case report.

BACKGROUND: Complex chromosomal rearrangements (CCRs) are constitutional structural rearrangements that involve three or more chromosomes or that have more than two breakpoints. CASE PRESENTATION: Here, we describe a four-way CCR involving chromosomes 4, 5, 6 and 8. The patient had mild multisystematic abnormalities during his development, including defects in his eyes and teeth, exomphalos and asthenozoospermia. His wife had two spontaneous abortions during the first trimester. The translocations in 4q27, 5q22, 6q22.3, and 8p11.2 were diagnosed by conventional cytogenetic analysis and confirmed by fluorescence in situ hybridization(FISH). After analysis using a SNP array, we defined three microdeletions, including 0.89 Mb on chromosome 4, 5.39 Mb on chromosome 5 and 0.43 Mb on chromosome 8. His mother had a chimera karyotype of 47, XXX[5]/45, X[4]/46, XX[91]; the other chromosomes were normal. After one cycle of in vitro fertility (IVF) treatment followed by preimplantation genetic diagnosis (PGD), they obtained two embryos, but neither was balanced. CONCLUSIONS: The patient's phenotype resulted from the CCR and microdeletion of chromosomes 4, 5 and 8. The couple decided to use artificial insemination by donor (AID) technology.