Ten-year trends in the incidence,clinical profile and outcomes of acute-onset endophthalmitis following combined pars plana vitrectomy and sutureless,glueless and flapless scleral fixation of intraocular lenses

International Ophthalmology - To evaluate the frequency and outcomes of acute-onset endophthalmitis following combined pars plana vitrectomy and scleral fixation of intraocular lens. We evaluated...     

Using Artificial Intelligence to Improve the Quality and Safety of Radiation Therapy

Within artificial intelligence, machine learning (ML) efforts in radiation oncology have augmented the transition from generalized to personalized treatment delivery. Although their impact on quality and safety of radiation therapy has been limited, they are increasingly being used throughout radiation therapy workflows. Various data-driven approaches have been used for outcome prediction, CT simulation, clinical decision support, knowledge-based planning, adaptive radiation therapy, plan validation, machine quality assurance, and process quality assurance; however, there are many challenges that need to be addressed with the creation and usage of ML algorithms as well as the interpretation and dissemination of findings. In this review, the authors present current applications of ML in radiation oncology quality and safety initiatives, discuss challenges faced by the radiation oncology community, and suggest future directions.     

Alterations in GABA(A) receptor mediated inhibition in adjacent dorsal midline thalamic nuclei in a rat model of chronic limbic epilepsy

There is evidence that the dorsal midline thalamus is involved in the seizures of limbic epilepsy. However, little is known about the inhibitory synaptic function in this region. In the present study, inhibitory postsynaptic currents (IPSCs) mediated by GABA(A) receptors were recorded from the mediodorsal (MD) and paraventricular (PV) nuclei from control and epileptic animals. In the MD, the spontaneous (s)IPSCs for epileptic animals had a lower frequency, prolonged rise time, prolonged decay, but unaltered net charge transfer compared with controls. The miniature (m)IPSC parameters were unaltered in the epileptic animals. In contrast, in the PV, both sIPSCs and mIPSCs in the epileptic animals were more frequent with larger amplitudes and there was an increase in the net charge transfer compared with controls. The rise times of the sIPSCs of the PV neurons were significantly prolonged, whereas the weighted decay time of the mIPSC was significantly shortened in epileptic animals. These findings suggest that the changes associated with inhibitory synaptic transmission in limbic epilepsy are not uniform across regions in the thalamus that are part of the seizure circuit.     

Effect of Microenvironmental pH Modulation on the Dissolution Rate and Oral Absorption of the Salt of a Weak Acid – Case Study of GDC-0810

Purpose

The purpose of this work is to investigate the effect of microenvironmental pH modulation on the in vitro dissolution rate and oral absorption of GDC-0810, an oral anti-cancer drug, in human.

Methods

The pH-solubility profile of GDC-0810 free acid and pH_max of its N-Methyl-D-glucamine (NMG) salt were determined. Precipitation studies were conducted for GDC-0810 NMG salt at different pH values. GDC-0810 200-mg dose NMG salt tablet formulations containing different levels of sodium bicarbonate as the pH modifier were tested for dissolution under the dual pH-dilution scheme. Three tablet formulations were evaluated in human as a part of a relative bioavailability study. A 200-mg dose of GDC-0810 was administered QD with low fat food.

Results

Intrinsic solubility of GDC-0810 free acid was found to be extremely low. The pH_max of the NMG salt suggested a strong tendency for form conversion to the free acid under GI conditions. In vitro dissolution profiles showed that the dissolution rate and extent of GDC-0810 increased with increasing the level of sodium bicarbonate in the formulation. The human PK data showed a similar trend for the geometric mean of C_max and AUC_0-t for formulations containing 5%, 10%, and 15% sodium bicarbonate, but the difference is not statistically significant.

Conclusion

Incorporation of a basic pH modifier, sodium bicarbonate, in GDC-0810 NMG salt tablet formulations enhanced in vitro dissolution rate of GDC-0810 via microenvironmental pH modulation. The human PK data showed no statistically significant difference in drug exposure from tablets containing 5%, 10%, and 15% sodium bicarbonate.