Consensus Recommendations for Studies of Outflow Facility and Intraocular Pressure Regulation Using Ex Vivo Perfusion Approaches.

Intraocular pressure (IOP) elevation is the primary risk factor and currently the main treatable factor for progression of glaucomatous optic neuropathy. In addition to direct clinical and living animal in vivo studies, ex vivo perfusion of anterior segments and whole eyes is a key technique for studying conventional outflow function as it is responsible for IOP regulation. We present well-tested experimental details, protocols, considerations, advantages, and limitations of several ex vivo model systems for studying IOP regulation.

Instrument-Free Point-of-Care Diagnostic for Leishmania Parasites.

Background/objective: Leishmaniasis is the second deadliest parasitic disease in the world, after malaria, with an estimated 1.6 million new cases each year. While cutaneous leishmaniasis can result in permanent scars from lesions after treatment, the mucocutaneous and visceral diseases can result in life-altering and life-threatening complications.

Versatile xylose and arabinose genetic switches development for yeasts.

Inducible transcription systems are essential tools in genetic engineering, where tight control, strong inducibility and fast response with cost-effective inducers are highly desired. However, existing systems in yeasts are rarely used in large-scale fermentations due to either cost-prohibitive inducers or incompatible performance. Here, we developed powerful xylose and arabinose induction systems in Saccharomyces cerevisiae, utilizing eukaryotic activators XlnR and AraR from Aspergillus species and bacterial repressors XylR and AraR.

Arthroscopic Chondral Nail Fixation for Treating Acetabular Cartilage Delamination Results in Improved Pain Relief at Minimum 2-Year Follow-Up in Patients With Femoroacetabular Impingement Syndrome: A Propensity-Matched Study.

Purpose: To investigate the clinical outcomes after arthroscopic chondral nail fixation for acetabular cartilage delamination (ACD) in patients with femoroacetabular impingement syndrome (FAIS), as well as the presentation of ACD on magnetic resonance imaging (MRI), at follow-up.

Methods: A retrospective review was performed between March 2021 and March 2022 at our institute. Patients undergoing primary hip arthroscopy for FAIS in whom ACD was diagnosed intraoperatively were included.

The Machine Learning Model for Predicting Inadequate Bowel Preparation Before Colonoscopy: A Multicenter Prospective Study.

Introduction: Colonoscopy is a critical diagnostic tool for colorectal diseases; however, its effectiveness depends on adequate bowel preparation (BP). This study aimed to develop a machine learning predictive model based on Chinese adults for inadequate BP.

Methods: A multicenter prospective study was conducted on adult outpatients undergoing colonoscopy from January 2021 to May 2023.

Safety, tolerability, pharmacokinetics and efficacy of HB0017, a humanized monoclonal antibody that targets interleukin-17A, in healthy participants and patients with moderate-to-severe plaque psoriasis.

Background: Several interleukin (IL)-17 inhibitors have been approved for the treatment of moderate-to-severe plaque psoriasis (PsO). There is still scope for the development of affordable treatments for PsO.

Objectives: To assess, in a phase Ia study, the safety, tolerability and pharmacokinetics (PK) of HB0017, a humanized monoclonal antibody that targets IL-17A, in healthy participants and patients with moderate-to-severe plaque PsO; and, in a phase Ib study, to assess the efficacy of HB0017 in patients with moderate-to-severe plaque PsO.

Early-Life Cardiovascular Risk Factor Trajectories and Vascular Aging in Midlife: A 30-Year Prospective Cohort Study.

Background: Vascular aging, as assessed by structural and functional arterial properties, is an independent predictor of cardiovascular outcomes. We aimed to explore the associations of individual cardiovascular risk factors from childhood to midlife and their accumulation over a 30-year span with vascular aging in midlife.

Methods: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, 2180 participants aged 6 to 18 years at baseline were followed for over 30 years.

mTORC1 upregulates B7-H3/CD276 to inhibit antitumor T cells and drive tumor immune evasion.

Identifying the mechanisms underlying the regulation of immune checkpoint molecules and the therapeutic impact of targeting them in cancer is critical. Here we show that high expression of the immune checkpoint B7-H3 (CD276) and high mTORC1 activity correlate with immunosuppressive phenotypes and worse clinical outcomes in 11,060 TCGA human tumors. We find that mTORC1 upregulates B7-H3 expression via direct phosphorylation of the transcription factor YY2 by p70 S6 kinase.

Recombinant Human Proteoglycan 4 (rhPRG4) Downregulates TNFα-Stimulated NFκB Activity and FAT10 Expression in Human Corneal Epithelial Cells.

Dry Eye Disease (DED) is a complex pathology affecting millions of people with significant impact on quality of life. Corneal inflammation, including via the nuclear factor kappa B (NFκB) pathway, plays a key etiological role in DED. Recombinant human proteoglycan 4 (rhPRG4) has been shown to be a clinically effective treatment for DED that has anti-inflammatory effects in corneal epithelial cells, but the underlying mechanism is still not understood.

Risk of Early Versus Later Rebleeding From Dural Arteriovenous Fistulas With Cortical Venous Drainage.

Background: Cranial dural arteriovenous fistulas with cortical venous drainage are rare lesions that can present with hemorrhage. A high rate of rebleeding in the early period following hemorrhage has been reported, but published long-term rates are much lower. No study has examined how risk of rebleeding changes over time.

Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms.

Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension.

Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

Background: New treatments are needed to reduce the risk of progression of coronavirus disease 2019 (Covid-19). Molnupiravir is an oral, small-molecule antiviral prodrug that is active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with molnupiravir started within 5 days after the onset of signs or symptoms in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed Covid-19 and at least one risk factor for severe Covid-19 illness.

Diffusion Tensor Imaging of Visual Pathway Abnormalities in Five Glaucoma Animal Models.

Purpose: To characterize the visual pathway integrity of five glaucoma animal models using diffusion tensor imaging (DTI).

Methods: Two experimentally induced and three genetically determined models of glaucoma were evaluated. For inducible models, chronic IOP elevation was achieved via intracameral injection of microbeads or laser photocoagulation of the trabecular meshwork in adult rodent eyes.

Optimizing Positivity Thresholds for a Risk-Adapted Screening Strategy in Colorectal Cancer Screening.

Introduction: Risk-adapted screening combining the Asia-Pacific Colorectal Screening score, fecal immunochemical test (FIT), and colonoscopy improved the yield of colorectal cancer screening than FIT. However, the optimal positivity thresholds of risk scoring and FIT of such a strategy warrant further investigation.

Methods: We included 3,407 participants aged 50-74 years undergoing colonoscopy from a colorectal cancer screening trial.

The development of - as anti-SARS-CoV-2 nanobody drug candidates.

Combating the COVID-19 pandemic requires potent and low-cost therapeutics. We identified a series of single-domain antibodies (i.e.

Negative-Pressure Isolation Mask for Endoscopic Examination During the Coronavirus Disease 2019 Pandemic: A Randomized Controlled Trial.

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, endoscopists have high risks of exposure to exhaled air from patients during gastroscopy. To minimize this risk, we transformed the oxygen mask into a fully closed negative-pressure gastroscope isolation mask. This study aimed to evaluate the effectiveness, safety, and feasibility of use of this mask during gastroscopy.

Natural History of Hemodynamics in Vertebrobasilar Disease: Temporal Changes in the VERiTAS Study Cohort.

Background And Purpose: The role of regional hypoperfusion as a contributor to stroke risk in atherosclerotic vertebrobasilar disease has recently been confirmed by the observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) Study. We examined the stability of hemodynamic status over time and its relationship to stroke risk in patients from this prospective cohort.

Methods: VERiTAS enrolled patients with recently symptomatic ≥50% atherosclerotic stenosis/occlusion of vertebral and/or basilar arteries.

Predominant classic circular-stapled double-tract reconstruction after totally laparoscopic proximal gastrectomy: safe, feasible, time-saving anastomoses by technical tie-up.

Background: The double-tract reconstruction (DTR) could be a preferable option in avoiding the postoperative esophageal reflux and anastomotic stenosis during totally laparoscopic proximal gastrectomy (TLPG). An optimal procedure to achieve the DTR in TLPG remains to be established.

Methods: During March 2018 to April 2019, 15 consecutive patients with gastric cancer in the upper third of the stomach underwent intracorporeal DTR after TLPG at our hospital.

A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry.

Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA.

Development and application of a rapid and sensitive LC-MS/MS method for simultaneous quantification of six diterpene lactones in rats after oral administration of Rhizoma Dioscoreae Bulbiferae extract.

Diterpene lactones have been considered as the main therapeutic and hepatotoxic constituents of Rhizoma Dioscoreae Bulbiferae in recent years. In this work, a simple, rapid and accurate LC-MS/MS method was established and validated to determine six diterpene lactones in rat plasma simultaneously, including Diosbulbin B (DIOB), Diosbulbin C (DIOC), Diosbulbin D (DIOD), Diosbulbin G (DIOG), Diosbulbin J (DIOJ) and Diosbulbin L (DIOL), after oral administration of Rhizoma Dioscoreae Bulbiferae extract. The six diterpene lactones, with the inclusion of two pairs of isomer (DIOB & D, DIOC & L), and Buspirone (internal standard, IS) were successfully separated using an XDB-C column with the gradient elution, consisting of water with 0.

Hypoperfusion Symptoms Poorly Predict Hemodynamic Compromise and Stroke Risk in Vertebrobasilar Disease.

Background and Purpose- Cerebral hypoperfusion symptoms (defined as symptoms related to change in position, effort or exertion, or recent change in antihypertensive medication) have been used in stroke studies as a surrogate for detecting hemodynamic compromise. However, the validity of these symptoms in identifying flow compromise in patients has not been well established. We examined whether hypoperfusion symptoms correlated with quantitative measurements of flow compromise in the prospective, observational VERiTAS study (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke).

A naturally occurring antiviral ribonucleotide encoded by the human genome.

Viral infections continue to represent major challenges to public health, and an enhanced mechanistic understanding of the processes that contribute to viral life cycles is necessary for the development of new therapeutic strategies . Viperin, a member of the radical S-adenosyl-L-methionine (SAM) superfamily of enzymes, is an interferon-inducible protein implicated in the inhibition of replication of a broad range of RNA and DNA viruses, including dengue virus, West Nile virus, hepatitis C virus, influenza A virus, rabies virus and HIV. Viperin has been suggested to elicit these broad antiviral activities through interactions with a large number of functionally unrelated host and viral proteins.

MR Imaging Grading System for Skull Base Chordoma.

Background And Purpose: Skull base chordoma has been widely studied in recent years, however, imaging characteristics of this tumor have not been well elaborated. The purpose of this study was to establish an MR imaging grading system for skull base chordoma.

Materials And Methods: In this study, 156 patients with skull base chordomas were retrospectively assessed.

Hemodynamic Features of Symptomatic Vertebrobasilar Disease.

Background And Purpose: Atherosclerotic vertebrobasilar disease is an important cause of posterior circulation stroke. To examine the role of hemodynamic compromise, a prospective multicenter study, Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS), was conducted. Here, we report clinical features and vessel flow measurements from the study cohort.