Cell-Penetrating Chaperone Nuc1 for Small- and Large-Molecule Delivery Into Retinal Cells and Tissues.

Purpose: There are currently no means available for the efficient delivery of recombinant proteins into retinal cells in vivo. Although cell-penetrating peptides have been somewhat effective in protein delivery to the retina, they generally require conjugation chemistry with the payload, negatively impacting function of the therapeutic protein. In this study, we developed a novel peptide (Nuc1) that acts as a chaperone for delivery of small and large molecules, including steroids, peptides, antibodies, recombinant proteins, and viruses (adeno-associated viruses [AAVs]) across biological membranes in vivo without the need for conjugation.

Comparative Analysis of Surgically Retrieved Sperms in Cases of Obstructive and Nonobstructive Azoospermia Treated for Infertility.

Background: Azoospermia is a highly evolving subject in the last few decades. In the past, use of donor sperm was the only option providing a realistic chance of conception for couples affected by azoospermia. Introduction of sperm retrieval techniques and assisted reproductive technologies, especially intracytoplasmic sperm injection (ICSI), has provided these men a chance to father their genetically own child and changed the management approach significantly.

Occurrence of extended-spectrum β-lactamase-producing bacteria in urban Clinton River habitat.

Objective: The aim of this study was to determine whether Clinton River water is contaminated with antibiotics and is a reservoir of antimicrobial-resistant bacteria.

Methods: Water samples were taken from two sites of Clinton River. Antimicrobial-resistant bacteria were enumerated on agar plates supplemented with six commonly used antibiotics.

Successful management of ureteric endometriosis by laparoscopic ureterolysis - A review and report of three further cases.

Objective: To review articles highlighting the effectiveness of conservative laparoscopic ureterolysis as a primary treatment option in patients with ureteric endometriosis and to report on a further three cases.

Patients And Methods: PubMed, EMBASE, Cochrane database were searched to identify articles reporting cases of laparoscopic management of ureteric endometriosis and, in particular management by ureterolysis. We further described three new cases of ureteric endometriosis managed at our institute.

G-quartet oligonucleotide mediated delivery of functional X-linked inhibitor of apoptosis protein into retinal cells following intravitreal injection.

There is currently no efficient method available for the delivery of full length functional proteins into the cytoplasm of retinal cells in vivo. Historically, the most successful approach for the treatment of retinal diseases has been intravitreal injection of antibodies or recombinant proteins, but this approach is not yet utilized for the delivery of proteins that require intracellular access for a therapeutic effect. Here we describe a platform for the delivery of functional proteins into ganglion cells, photoreceptors and retinal pigment epithelium via intravitreal injection.

Microscopic varicocelectomy as a treatment option for patients with severe oligospermia.

Purpose: Many studies have shown improved semen parameters after varicocele surgery; however, the benefit in terms of improved pregnancy rates and live births is still disputed in cases of severe oligoasthenozoospermia (OAS). The present study evaluated the outcome of microscopic subinguinal varicocelectomy in terms of the spontaneous pregnancy rate in patients with severe OAS.

Materials And Methods: This was a retrospective, observational, analytic study of 56 men with OAS who underwent microscopic varicocelectomy at our center between 2008 and 2015.

Occurrence of Multidrug Resistant Extended Spectrum Beta-Lactamase-Producing Bacteria on Iceberg Lettuce Retailed for Human Consumption.

Antibiotic resistance in bacteria is a global problem exacerbated by the dissemination of resistant bacteria via uncooked food, such as green leafy vegetables. New strains of bacteria are emerging on a daily basis with novel expanded antibiotic resistance profiles. In this pilot study, we examined the occurrence of antibiotic resistant bacteria against five classes of antibiotics on iceberg lettuce retailed in local convenience stores in Rochester, Michigan.

Catalase therapy corrects oxidative stress-induced pathophysiology in incipient diabetic retinopathy.

Purpose: Preclinical studies have highlighted retinal oxidative stress in the pathogenesis of diabetic retinopathy. We evaluated whether a treatment designed to enhance cellular catalase reduces oxidative stress in retinal cells cultured in high glucose and in diabetic mice corrects an imaging biomarker responsive to antioxidant therapy (manganese-enhanced magnetic resonance imaging [MEMRI]).

Methods: Human retinal Müller and pigment epithelial cells were chronically exposed to normal or high glucose levels and treated with a cell-penetrating derivative of the peroxisomal enzyme catalase (called CAT-SKL).

In Vivo Role of TLR2 and MyD88 Signaling in Eliciting Innate Immune Responses in Staphylococcal Endophthalmitis.

Purpose: The purpose of this study was to investigate the protective mechanisms evoked by TLR2 and MyD88 signaling in bacterial endophthalmitis in vivo.

Methods: Endophthalmitis was induced in wild-type (WT), TLR2(-/-), MyD88(-/-), and Cnlp(-/-) mice by intravitreal injections of a laboratory strain (RN6390) and two endophthalmitis isolates of Staphylococcus aureus. Disease progression was monitored by assessing corneal and vitreous haze, bacterial burden, and retinal tissue damage.

Pathogenicity of ocular isolates of Acinetobacter baumannii in a mouse model of bacterial endophthalmitis.

Purpose: To determine the virulence properties of ocular isolates of Acinetobacter baumannii in causing endophthalmitis in a mouse model.

Methods: Endophthalmitis was induced by intravitreal injections of the bacteria into C57BL/6 (B6) mouse eyes. The disease progression was monitored by ophthalmoscopic, electroretinography (ERG), histologic, cell death (TUNEL labeling), and microbiological parameters.

Virulence properties of multidrug resistant ocular isolates of Acinetobacter baumannii.

Purpose: Acinetobacter (A.) baumannii is an opportunistic pathogen and has been reported as a causative agent of ocular infections. The aim of this study is to identify virulence properties (biofilm formation, adhesion, invasion and cytotoxicity) and antibiotic resistance among A.

FK506 binding protein 12 deficiency in endothelial and hematopoietic cells decreases regulatory T cells and causes hypertension.

Patients treated with the immunosuppressive drug tacrolimus (FK506), which binds FK506 binding protein 12 (FKBP12) and then inhibits the calcium-dependent phosphatase calcineurin, exhibit decreased regulatory T cells, endothelial dysfunction, and hypertension; however, the mechanisms and whether altered T-cell polarization play a role are unknown. Tacrolimus treatment of mice for 1 week dose-dependently decreased splenic CD4(+)/FoxP3(+) (regulatory T cells), increased splenic CD4(+)/IL-17(+) (T-helper 17) cells, and caused endothelial dysfunction and hypertension. To determine the mechanisms, we crossed floxed FKBP12 mice with Tie2-Cre mice to generate offspring lacking FKBP12 in endothelial and hematopoietic cells only (FKBP12EC knockout [KO]).