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Purpose: To develop and validate a deep learning system (DLS) for estimation of vertical cup-to-disc ratio (vCDR) in ultra-widefield (UWF) and smartphone-based fundus images., Methods: A DLS consisting of two sequential convolutional neural networks (CNNs) to delineate optic disc (OD) and optic cup (OC) boundaries was developed using 800 standard fundus images from the public REFUGE data set. The CNNs were tested on 400 test images from the REFUGE data set and 296 UWF and 300 smartphone-based images from a teleophthalmology clinic. vCDRs derived from the delineated OD/OC boundaries were compared with optometrists' annotations using mean absolute error (MAE). Subgroup analysis was conducted to study the impact of peripapillary atrophy (PPA), and correlation study was performed to investigate potential correlations between sectoral CDR (sCDR) and retinal nerve fiber layer (RNFL) thickness., Results: The system achieved MAEs of 0.040 (95% CI, 0.037-0.043) in the REFUGE test images, 0.068 (95% CI, 0.061-0.075) in the UWF images, and 0.084 (95% CI, 0.075-0.092) in the smartphone-based images. There was no statistical significance in differences between PPA and non-PPA images. Weak correlation (r = -0.4046, P < 0.05) between sCDR and RNFL thickness was found only in the superior sector., Conclusions: We developed a deep learning system that estimates vCDR from standard, UWF, and smartphone-based images. We also described anatomic peripapillary adversarial lesion and its potential impact on OD/OC delineation., Translational Relevance: Artificial intelligence can estimate vCDR from different types of fundus images and may be used as a general and interpretable screening tool to improve community reach for diagnosis and management of glaucoma.

Aquatic environments, under frequent anthropogenic pressure, could serve as reservoirs that provide an ideal condition for the acquisition and dissemination of antibiotic resistance genetic determinants. We investigated the prevalence and diversity of antibiotic-resistant Escherichia coli by focusing on their genetic diversity, virulence, and resistance genes in anthropogenic-impacted Larut River. The abundance of E. coli ranged from (estimated count) Est 1 to 4.7 × 10 5 (colony-forming units per 100 ml) CFU 100 ml -1 to Est 1 to 4.1 × 10 5 CFU 100 ml -1 with phylogenetic group B1 (46.72%), and A (34.39%) being the most predominant. The prevalence of multiple antibiotic resistance phenotypes of E. coli , with the presence of tet and sul resistance genes, was higher in wastewater effluents than in the river waters. These findings suggested that E. coli could be an important carrier of the resistance genes in freshwater river environments. The phylogenetic composition of E. coli and resistance genes was associated with physicochemical properties and antibiotic residues. These findings indicated that the anthropogenic inputs exerted an effect on the E. coli phylogroup composition, diversification of multiple antibiotic resistance phenotypes, and the distribution of resistance genes in the Larut River., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bong, Low, Chai and Lee.)

Post Endoscopic Retrograde Cholangiopancreatography (ERCP) pneumoperitoneum is commonly associated with perforated viscus but is rarely associated with benign causes. We present a case of 29 years old lady who underwent ERCP, who was found to have benign pneumoperitoneum subsequently. She was treated conservatively and recovered without complication. Although rare, post ERCP pneumoperitoneum of benign causes should be investigated as the course of treatment and outcome differ largely.

Purpose: Genome-wide association studies have identified several genes associated with glaucoma. However, their roles in the pathogenesis of glaucoma remain unclear, particularly their effects on retinal nerve fiber layer (RNFL) thickness. The aim of this study was to investigate the associations between the identified glaucoma risk genes and RNFL thickness., Methods: A total of 3843 participants (7,020 healthy eyes) were enrolled from the Singapore Epidemiology of Eye Diseases (SEED) study, a population-based study composing of three major ethnic groups-Malay, Indian, and Chinese-in Singapore. Ocular examinations were performed, and spectral-domain optical coherence tomography (SD-OCT) was used to measure circumpapillary RNFL thickness. We selected 35 independent glaucoma-associated genetic loci for analysis. An linear regression model was conducted to determine the association of these variants with circumpapillary RNFL, assuming an additive genetic model. We conducted association analysis in each of the three ethnic groups, followed by a meta-analysis of them., Results: The mean age of the included participants was 59.4 ± 8.9 years, and the mean RFNL thickesss is 92.3 ± 11.2 µm. In the meta-analyses, of the 35 glacuoma loci, we found that only SIX6 was significantly associated with reduction in global RNFL thickness (rs33912345; β = -1.116 um per risk allele, P = 1.64E-05), and the effect size was larger in the inferior RNFL quadrant (β = -2.015 µm, P = 2.9E-6), and superior RNFL quadrant (β = -1.646 µm, P = 6.54E-5). The SIX6 association were consistently observed across all three ethnic groups. Other than RNFL, we also found several genetic varaints associated with vertical cuo-to-disc ratio (ATOH7, CDKN2B-AS1, and TGFBR3-CDC7), rim area (SIX6 and CDKN2B-AS1), and disc area (SIX6, ATOH7, and TGFBR3-CDC7). The association of SIX6 rs33912345 with NRFL thickness remained similar after further adjusting for disc area and 3 other disc parameter associated SNPs (ATOH7, CDKN2B-AS1, and TGFBR3-CDC7)., Conclusions: Of the 35 glaucoma identified risk loci, only SIX6 is significantly and independently associated with thinner RNFL. Our study further supports the involvement of SIX6 with RNFL thickness and pathogensis of glaucoma.

Families with multiple male children with intellectual disability (ID) are usually suspected of having disease due to a X-linked mode of inheritance and genetic studies focus on analysis of segregating variants in X-linked genes. However, the genetic cause of ID remains elusive in approximately 50% of affected individuals. Here, we report the analysis of next-generation sequencing data in 274 affected individuals from 135 families with a family history suggestive of X-linked ID. Genetic diagnoses were obtained for 19% (25/135) of the families, and 24% (33/135) had a variant of uncertain significance. In 12% of cases (16/135), the variants were not shared within the family, suggesting genetic heterogeneity and phenocopies are frequent. Of all the families with reportable variants (43%, 58/135), we observed that 55% (32/58) were in X-linked genes, but 38% (22/58) were in autosomal genes, while the remaining 7% (4/58) had multiple variants in genes with different modes on inheritance. This study highlights that in families with multiple affected males, X linkage should not be assumed, and both individuals should be considered, as different genetic etiologies are common in apparent familial cases.

Allergic contact dermatitis (ACD) is an increasing problem in children. We sought to investigate the extent of haptens or contact allergens present in baby cosmetic products. Computer programming scripts were written to web-scrape UK supermarkets and pharmacies. In total, 438 unique 'baby products' were identified, and constituent ingredient information was extracted. Data were cross-referenced against 10 standardized patch test reference series. We found that 88% of products had at least one reference contact allergen. There was a mean of 2.21 (range 1-15) reference allergens per product. The most abundant compounds were parabens, fragrances, cetyl/steryl alcohol, methylisothiazolinone, sodium lauryl sulfate and lanolin alcohol. Branded products and those marketed as 'sensitive/gentle/organic/fragrance-free' appeared to contain a greater number of reference allergens than those not marketed as such. This study highlights the increasing number of cosmetic products targeted to children in the UK, and the extent of potential allergens present in these products., (© 2018 British Association of Dermatologists.)

Aim: With an aging Singapore population, there is an increasing demand for dementia care. The present study aimed to evaluate the effectiveness and cost-effectiveness of the Primary Care Dementia Clinic (PCDC) in comparison with the Memory Clinic (MC; hospital-based) and other polyclinics., Methods: A quasi-experimental design was implemented. Effectiveness of PCDC was assessed through caregiver satisfaction, quality of life (caregiver-rated) and adverse events rates. Quality-of-Life measures using the EuroQol 5 Dimension Questionnaire (EQ-5D) at baseline, 6 months and 12 months was assessed. Costs were calculated from a societal perspective. The incremental cost-effectiveness of the PCDC was compared with MC and other polyclinics., Results: The present study showed that quality of life and the rate of adverse events at 12 months were similar between the three groups. Caregiver satisfaction at 12 months was higher in the PCDC group when compared with other polyclinics. There were no observed differences in societal cost between the three groups. At 6-month follow up, direct medical costs for PCDC were significantly lower that of other polyclinics. At 12-month follow up, PCDC patients had higher Quality Adjusted Life Years (QALYs) compared with the MC group., Conclusion: PCDC provided effective care, similar to care at MC and better than care at other polyclinics. Caregiver satisfaction was higher for the PCDC group, and PCDC patients had lower direct medical costs at 6-month follow up. Given these findings, adopting a PCDC model in other polyclinics in Singapore can be beneficial for optimal right siting of patients. Geriatr Gerontol Int 2018; 18: 479-486., (© 2017 Japan Geriatrics Society.)

During differentiation, human embryonic stem cells (hESCs) shut down the regulatory network conferring pluripotency in a process we designated pluripotent state dissolution (PSD). In a high-throughput RNAi screen using an inclusive set of differentiation conditions, we identify centrally important and context-dependent processes regulating PSD in hESCs, including histone acetylation, chromatin remodeling, RNA splicing, and signaling pathways. Strikingly, we detected a strong and specific enrichment of cell-cycle genes involved in DNA replication and G2 phase progression. Genetic and chemical perturbation studies demonstrate that the S and G2 phases attenuate PSD because they possess an intrinsic propensity toward the pluripotent state that is independent of G1 phase. Our data therefore functionally establish that pluripotency control is hardwired to the cell-cycle machinery, where S and G2 phase-specific pathways deterministically restrict PSD, whereas the absence of such pathways in G1 phase potentially permits the initiation of differentiation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Considerable interest has arisen in precision fabrication of cell bearing scaffolds and structures by free form fabrication. Gelatin is an ideal material for creating cell entrapping constructs, yet its application in free form fabrication remains challenging. We demonstrate the use of gelatin, crosslinked with microbial transglutaminase (mTgase), as a material to print cell bearing hydrogels for both 2-dimensional (2-D) precision patterns and 3-dimensional (3-D) constructs. The precision patterning was attained with 3 % gelatin and 2 % high molecular weight poly (ethylene oxide) (PEO) whereas 3-D constructs were obtained using a 5 % gelatin solution. These hydrogels, referred to as "bioinks" supported entrapped cell growth, allowing cell spreading and proliferation for both HEK293 cells and Human Umbilical Vein Endothelial Cells (HUVECs). These bioinks were shown to be dispensable by robotic precision, forming patterns and constructs that were insoluble and of suitable stiffness to endure post gelation handling. The two bioinks were further characterized for fabrication parameters and mechanical properties.

A method has been developed to induce and retain a contractile phenotype for vascular smooth muscle cells, as the first step towards the development of a biomimetic blood vessel construct with minimal compliance mismatch. Melt spun PCL fibers were deposited on a mandrel to form aligned fibers of 10 μm in diameter. The fibers were bonded into aligned arrangement through dip coating in chitosan solution. This formed a surface of parallel grooves, 10 μm deep by 10 μm across, presenting a surface layer of chitosan to promote cell surface interactions. The aligned fiber surface was used to culture cells present in the vascular wall, in particular fibroblasts and smooth muscle cells. This topography induced "surface guidance" over the orientation of the cells, which adopted an elongated spindle-like morphology, whereas cells on the unpatterned control surface did not show such orientation, assuming more rhomboid shapes. The preservation of VSMC contractile phenotype on the aligned scaffold was demonstrated by the retention of α-SMA expression after several days of culture. The effect was assessed on a prototype vascular graft prosthesis fabricated from polylactide caprolactone; VSMCs aligned longitudinally along a fiberless tube, whereas, for the aligned fiber coated tubes, the VSMCs aligned in the required circumferential orientation.

Background: Kiwifruit is high in pectic polysaccharides and dietary fiber. This study aimed to find out how the ingestion of kiwifruit will affect intestinal microbiota populations, namely Lactobacillus, Bacteroides, Clostridium, Bifidobacterium, and Enterococcus., Methods: Freeze dried kiwifruit (equivalent of two fresh kiwifruits) was given to each of the six subjects daily for four days. Faecal samples were collected before, during and after kiwifruit consumption. The faecal bacteria were enumerated by qPCR and RT qPCR methods., Results: The effect of the kiwifruit on intestinal microbiota profile varied between individuals; in general, the kiwifruit demonstrated a prebiotic effect of promoting the content of faecal lactobacilli and bifidobacteria (as compared to the baselines of the same individual before consumption) for as long as the fruit was consumed. The effect was however transient, the levels of the two bacteria returned near to that of the baselines upon cessation of consumption., Conclusion: Kiwifruit is a prebiotic in selectively enhancing the growth of intestinal lactic acid bacteria.