Structure-guided optimization of small molecules targeting the yeast casein kinase, Yck2, as a therapeutic strategy to combat Candida albicans.

is the most common cause of life-threatening fungal infection in the developed world but remains a therapeutic challenge. Protein kinases have been rewarding drug targets across diverse indications but remain untapped for antifungal development. Previously, screening kinase inhibitors against revealed a 2,3-aryl-pyrazolopyridine, GW461484A (GW), which targets casein kinase 1 (CK1) family member Yck2.

Plant nutrient concentrations inform white-tailed deer diet limitations.

Management of large herbivores often involves increasing availability of forages sufficient in nutrient density to allow animals to meet dietary demands. Nutritional carrying capacity (NCC) models commonly are used to compare plant communities and management strategies, but failure to use the most limiting nutrient could result in overestimating NCC. Moreover, the relationship between limiting nutrients often is not considered, which may influence the utility of NCC models based on a single nutrient, especially when herbivores must simultaneously meet multiple constraints.

Stereotactic radiosurgery for fourth ventricle brain metastases: tumor control outcomes and the need for CSF diversion. Patient series.

Background: Stereotactic radiosurgery is a favorable alternative to surgery for intracranial cerebral metastases. Fourth ventricle (V4) metastases are challenging because of the location and surrounding structures, with a high risk for obstructive hydrocephalus and brainstem compression. Here, the authors evaluate the effectiveness in terms of safety, tumor control rates, and permanent cerebrospinal fluid (CSF) diversion of primary Gamma Knife radiosurgery (GKRS) in treating V4 metastases.

Prochlorperazine maleate versus placebo for the prevention of acute mountain sickness: study protocol for a randomized controlled trial.

Background: Acute mountain sickness (AMS) is a debilitating condition that individuals may develop on ascent to high altitude. It is characterized by headache, nausea, vomiting, dizziness, and fatigue with the potential to progress to fatal disease. Although the pathophysiology of AMS remains unclear, proposed mechanisms are hypothesized to be similar to migraine.