Ehlers-Danlos syndromes (EDSs) are a group of inherited connective tissue disorders, and among them, classical EDS (cEDS) and hypermobile EDS (hEDS) are the most common. Mitral valve prolapse (MVP) and aortic root dilation (ARD) have previously been reported to occur at an increased frequency within cEDS and hEDS. More recently, a study performed in the pediatric population did not show increased prevalence (Ritter et al., American Journal of Medical Genetics Part A, 173(6), 1467-1472, 2017). The purpose of this study was to review a large population of individuals with cEDS, hEDS, and hypermobility spectrum disorders to determine the frequency of MVP and ARD. A retrospective chart review of 209 individuals with echocardiograms was performed. Overall, 6.4% (13/209) had MVP and 1.6% (3/189) were found to have ARD. Although the presence of MVP is higher than what has been reported in the general population, no patients had severe MVP or required surgical intervention. No patients in this cohort had an aortic root diameter requiring surgical repair. Based on the results of this study and previous studies, routine echocardiograms to assess for valvular diseases and ARD may not be necessary unless warranted by presence of symptoms or family history.

The tumor microenvironment is complex with the cancer stem cell (CSC) as a member within its community. This population possesses the capacity to self-renew and to cause cellular heterogeneity of the tumor. CSCs are resistant to conventional anti-proliferative drugs. In order to be curative, it is imperative that CSCs must be eliminated by cancer therapy. A variety of dietary phytochemicals and repositioned drugs can act synergistically with conventional anti-cancer agents. In this review, we advocate the development of a novel approach, namely combination therapy by incorporating both phytochemicals and repositioned drugs to target CSCs. We cover select dietary phytochemicals (curcumin, resveratrol, EGCG, genistein) and repurposed drugs (metformin, niclosamide, thioridazine, chloroquine). Five of the eight (curcumin, resveratrol, EGCG, genistein, metformin) are listed in "The Halifax Project", that explores "the concept of a low-toxicity 'broad-spectrum' therapeutic approach that could simultaneously target many key pathways and mechanisms" [1]. For these compounds, we discuss their mechanisms of action, in which models their anti-CSC activities were identified, as well as advantages, challenges and potentials of combination therapy.

C3 is a predatory strain of Gram-negative gliding bacteria that produces antifungal antibiotics by the polyketide synthetic pathway. Outer membrane vesicles (OMV) are formed as a stress response and can deliver virulence factors to host cells. The production of OMV by C3 and their role in antifungal activity are reported here. Vesicles in the range of 130 to 150 nm in diameter were discovered in the cell-free supernatants of C3 cultures. These OMV contain molecules characteristic of bacterial outer membranes, such as lipopolysaccharide and phospholipids. In addition, they contain chitinase activity and essentially all of the heat-stable antifungal activity in cell supernatants. We show here that C3 OMV can directly inhibit growth of the yeast as well as that of the filamentous fungus The activity is dependent on physical contact between OMV and the cells. Furthermore, fluorescent lipid labeling of C3 OMV demonstrated transfer of the membrane-associated probe to yeast cells, suggesting the existence of a mechanism of delivery for membrane-associated molecules. Mass spectrometric analysis of C3 OMV extracts indicates the presence of molecules with molecular weights identical to some of the previously identified antifungal products of C3. These data together suggest that OMV act as an important remote mobile component of predation by The data presented here suggest a newly discovered function of outer membrane vesicles (OMV) that are produced from the outer membrane of the bacterial species strain C3. We show that these OMV can be released from the surface of the cells to deliver antibiotics to target fungal organisms as a mechanism of killing or growth inhibition. Understanding the role of OMV in antibiotic delivery can generally lead to improved strategies for dealing with antibiotic-resistant organisms. These results also add to the evidence that some bacterially produced antibiotics can be discovered and purified using methods designed for isolation of nanoscale vesicles. Information on these systems can lead to better identification of active molecules or design of delivery vehicles for these molecules.

Objective: Pre-exposure prophylaxis (PrEP) is a recommended strategy for HIV prevention, yet PrEP prescribing rates in primary care remain low. The aim of this study was to further describe the current knowledge, attitudes, and prescribing behaviors of HIV PrEP in primary care providers with a focus on the perceived barriers and facilitators to PrEP prescribing. Methods: Cross-sectional survey of primary care providers at rural and suburban practices in a large academic institution. Results: Survey response rate was 48.0% (n = 134). Most respondents (96.3%) reported little clinical experience in care of persons living with HIV. Respondents self-reported positive attitudes and high overall knowledge of PrEP with low prescribing rates and less comfort with lab testing. More respondents are asked about PrEP by patients (54%) than start conversations about PrEP with patients (39%). Family Physicians and providers 5 to 10 years from completion of training overall reported higher knowledge, attitudes and prescribing behaviors. Lack of PrEP education was identified as the greatest barrier and an electronic medical record order set as the greatest facilitator to prescribing PrEP. Conclusions: With the goal to end the HIV epidemic, PrEP provision in nonurban primary care settings may be an important strategy for increased access to PrEP and reduced HIV transmission. This study, which includes a variety of providers that possess high knowledge, yet low experience prescribing PrEP, likely demonstrates the limitations of interventions which solely focus on provider education. System-based practice solutions, such as order sets, may be needed to target infrequent prescribers of PrEP.