The relationship between dry eye disease and human microbiota: A review of the science.

A complex relationship exists between human microbiota and the risk for ophthalmic disease. While the homeostatic composition of human microbiota is still being established, including what defines dysbiosis (i.e. changes in diversity and abundance), pilot research has begun to identify the potential influence of demographics, geography, and co-morbidities on the microbiota and describe their impact on ocular health. This review specifically focuses on the scientific relationships of the human oral and gut microbiota to dry eye disease (DED), a set of conditions impacting the tear film and ocular surface. Although data are sparse and often conflict across studies, the literature generally supports associations between microbial imbalance (dysbiosis) and DED and alterations in microbial diversity and abundance to specific aspects of DED. This review examines the relevant science and mechanistic relationships linking gut and oral dysbiosis and DED. Various physiochemical factors and therapeutic approaches that alter microbiota, including medications and fecal transplants are examined in relation to DED.

Endoplasmic Reticulum Stress Disrupts Mitochondrial Bioenergetics, Dynamics and Causes Corneal Endothelial Cell Apoptosis.

Purpose: Endoplasmic reticulum (ER) and mitochondrial stress are independently associated with corneal endothelial cell (CEnC) loss in many corneal diseases, including Fuchs' endothelial corneal dystrophy (FECD). However, the role of ER stress in mitochondrial dysfunction contributing to CEnC apoptosis is unknown. The purpose of this study is to explore the crosstalk between ER and mitochondrial stress in CEnC. Methods: Human corneal endothelial cell line (HCEnC-21T) and human corneal endothelial tissues were treated with ER stressor tunicamycin. ER stress-reducing chemical 4-phenyl butyric acid (4-PBA) was used in HCEnC-21T after tunicamycin. Fuchs' corneal endothelial cell line (F35T) was used to determine differential activation of ER stress with respect to HCEnC-21T at the baseline. ER stress, mitochondrial-mediated intrinsic apoptotic, mitochondrial fission, and fusion proteins were determined using immunoblotting and immunohistochemistry. Mitochondrial bioenergetics were assessed by mitochondrial membrane potential (MMP) loss and ATP production at 48 hours after tunicamycin. Mitochondria dynamics (shape, area, perimeter) were also analyzed at 24 hours using transmission electron microscopy. Results: Treatment of HCEnC-21T cell line with tunicamycin activated three ER stress pathways (PERK-eIF2α-CHOP, IRE1α-XBP1, and ATF6), reduced cell viability, upregulated mitochondrial-mediated intrinsic apoptotic molecules (cleaved caspase 9, caspase 3, PARP, Bax, cytochrome C), downregulated anti-apoptotic Bcl-2 protein, initiated mitochondrial dysfunction by loss of MMP and lowering of ATP production, and caused mitochondrial swelling and fragmentation with increased expression of mitochondrial fission proteins (Fis1 and p-Drp1). Fuchs' CEnC (F35T) cell line also showed activation of the ER stress-related proteins (p-eIF2α, GRP78, CHOP, XBP1) compared to HCEnC-21T at the baseline. The 4-PBA ameliorated cell loss and reduced cleaved caspase 3 and 9, thereby rescuing tunicamycin-induced cell death but not mitochondrial bioenergetics in HCEnC-21T cell line. Conclusions: Tunicamycin-induced ER stress disrupts mitochondrial bioenegetics, dynamics and contributes to the loss of CEnC viability. This novel study highlights the importance of ER-mitochondria crosstalk and its contribution to CEnCs apoptosis, seen in many corneal diseases, including FECD.

Surgical External Iliac Artery Access for Transcatheter Aortic Valve Replacement Is a Safe, Suitable Alternative to Common Femoral Artery Access.

Background Many patients undergoing transcatheter aortic valve replacement (TAVR) have peripheral artery disease necessitating surgical access. This study reviews the preoperative risk factors, procedural characteristics, and outcomes in patients undergoing surgical common femoral artery (CFA) and external iliac artery (EIA) access through a retro-inguinal groin incision for TAVR. Methods A single-center TAVR database was retrospectively analyzed for patients undergoing surgical cutdown (January 1, 2016 - December 31, 2020). Access sites were evaluated on preoperative imaging. Data on demographics, imaging, procedural characteristics, and outcomes were collected. The vascular surgeon selected the cutdown site. Results A hundred and thirty TAVR patients had surgical cutdown. The choice of access site was either the common femoral artery (82 patients, 63%) or the iliac artery (48 patients, 37%). There was no difference in age, BMI, or medical risk factors. There was no difference in iliac diameter or circumferential iliac calcium. In the iliac group, there was a smaller mean CFA size and a higher incidence of circumferential CFA calcium. In the femoral group, there was: a lower mean sheath-to-CFA ratio, a trend toward increased unplanned endarterectomy, and a higher incidence of 30-day readmission. There was no difference in adjunct procedure use. Conclusion EIA surgical access had similar complication rates and length of stay with a reduced tendency for unplanned endarterectomy when compared to CFA access. The EIA is a suitable access site for TAVR in select patients.

Complete Genome Sequence of Escherichia coli ML35.

We report here the complete genome sequence of Escherichia coli strain ML35. We assembled PacBio reads into a single closed contig with 169× mean coverage and then polished this contig using Illumina MiSeq reads, yielding a 4,918,774-bp sequence with 50.8% GC content.