A small molecule UPR modulator for diabetes identified by high throughput screening

Unfolded protein response (UPR) is a stress response that is specific to the endoplasmic reticulum (ER). UPR is activated upon accumulation of unfolded (or misfolded) proteins in the ER's lumen to restore protein folding capacity by increasing the synthesis of chaperones. In addition, UPR also enhances degradation of unfolded proteins and reduces global protein synthesis to alleviate additional accumulation of unfolded proteins in the ER. Herein, we describe a cell-based ultra-high throughput screening (uHTS) campaign that identifies a small molecule that can modulate UPR and ER stress in cellular and

Modified Goldmann prism intraocular pressure measurement accuracy and correlation to corneal biomechanical metrics: multicentre randomised clinical trial.

PURPOSE: Clinically evaluate intraocular pressure (IOP) measurements taken with a Goldmann applanation tonometer (GAT) prism and a modified surface Goldmann prism examining measurement differences correlated to central corneal thickness (CCT) and corneal hysteresis (CH) values. DESIGN: Prospective, open-label, randomised, controlled, multicentre reference device accuracy analysis. METHODS: A GAT and a modified surface GAT prism measured IOP on 243 unique eyes. The study design and methodology complied with International Standard Organization (ISO) tonometer evaluation guidelines, except the inclusion of thin (<500 µm) and thick (>600 µm) corneas. All eyes were randomised to IOP measurement by one of five standard Goldmann prisms and five modified prisms. Pressures were measured by six investigators, two times with each prism for a total of 1936 IOP measurements. Analysis included a multiple linear regression including CCT and CH correlation. RESULTS: The difference in IOP measurements of the standard and modified Goldmann prisms correlated well to CCT particularly in thin (<500 µm) and thick (>600 µm) corneas (R2=0.404, p=0.007). Corneal hysteresis (CH) also significantly correlated to the difference in prism measurements (R2=0.125, p=0.039). There was no significant overall mean IOP bias between the two prisms (+0.43 mm Hg in modified, p=0.19). DISCUSSION: The paired IOP measurement difference between GAT and a modified surface Goldmann replacement prism indicated a statistically significant correlation to CCT and CH. A simple modified replacement prism for any Goldmann-type tonometer may significantly improve IOP measurement accuracy by minimising corneal biomechanical errors associated with CCT and CH. TRIAL REGISTRATION NUMBER: NCT02990169 and NCT02989909.

Laparoscopic colon resection: is it being utilized?

Since its inception, the use of laparoscopy for colon surgery has slowly increased, albeit at a slower rate than for cholecystectomy. Initial concerns about the safety and efficacy of laparoscopy have been addressed, and it is now known to have several potential short-term and long-term benefits for the patient. Early studies likely underestimated use of laparoscopy because of coding error. Currently, 40% to 50% of colectomies in the United States are performed laparoscopically, with a 10% to 20% rate of conversion to an open operation. The definitions oflaparoscopy and conversion to open remain at the discretion of the surgeons and their coders. Disparities still exist among use based on several patient, hospital, and surgeon factors. In the future, we will likely see a continuing increase in use as the new generation of surgeons enters practice, and there will be an increasing role for laparoscopy in rectal surgery. The benefit and extent of robotic surgery, natural orifice surgery, and single-incision surgery for minimally invasive colectomies are yet to be defined.

Functional organization of the circuits connecting the cerebral cortex and the basal ganglia: implications for the role of the basal ganglia in epilepsy.

The basal ganglia are composed of a set of forebrain structures implicated in the adaptive control of behaviour. These structures process information originating from the entire cerebral cortex, as well as from nonspecific thalamic nuclei and the amygdala. In turn, they redistribute the integrated signals toward thalamic and brainstem nuclei related to motor, premotor, prefrontal and limbic cortical areas. During the two last decades, there has been increasing experimental evidence that the basal ganglia circuitry may be part of a remote control system influencing the spread of epileptic seizures. In the present article, we review the basic principles of the functional organization of the basal ganglia and provide experimental data on the activity that is transmitted by the cerebral cortex to the input stage of the basal ganglia during absence seizures. The functional organization of the basal ganglia supports the current hypothesis that these structures can dynamically control generalized seizures through their input-output relationships.