An Integrated Assessment of the Introduction of Lionfish (Pterois volitans/miles complex) to the Western Atlantic Ocean.

Lionfish (Pterois volitans/miles complex) are venomous coral reef fishes from the Indian and western Pacific oceans that are now found in the western Atlantic Ocean. Adult lionfish have been observed from Miami, Florida to Cape Hatteras, North Carolina, and juvenile lionfish have been observed off North Carolina, New York, and Bermuda. The large number of adults observed and the occurrence of juveniles indicate that lionfish are established and reproducing along the southeast United States coast. Introductions of marine species occur in many ways. Ballast water discharge, a very common method of introduction for marine invertebrates, is responsible for many freshwater fish introductions. In contrast, most marine fish introductions result from intentional stocking for fishery purposes. Lionfish, however, likely were introduced via unintentional or intentional aquarium releases, and the introduction of lionfish into United States waters should lead to an assessment of the threat posed by the aquarium trade as a vector for fish introductions. Currently, no management actions are being taken to limit the effect of lionfish on the southeast United States continental shelf ecosystem. Further, only limited funds have been made available for research. Nevertheless, the extent of the introduction has been documented and a forecast of the maximum potential spread of lionfish is being developed. Under a scenario of no management actions and limited research, three predictions are made: ● With no action, the lionfish population will continue to grow along the southeast United States shelf. ● Effects on the marine ecosystem of the southeast United States will become more noticeable as the lionfish population grows. ● There will be incidents of lionfish envenomations of divers and/or fishers along the east coast of the United States. Removing lionfish from the southeast United States continental shelf ecosystem would be expensive and likely impossible. A bounty could be established that would encourage the removal of fish and provide specimens for research. However, the bounty would need to be lower than the price of fish in the aquarium trade (~$25-$50 each) to ensure that captured specimens were from the wild. Such a low bounty may not provide enough incentive for capturing lionfish in the wild. Further, such action would only increase the interaction between the public and lionfish, increasing the risk of lionfish envenomations. As the introduction of lionfish is very likely irreversible, future actions should focus on five areas. 1) The population of lionfish should be tracked. 2) Research should be conducted so that scientists can make better predictions regarding the status of the invasion and the effects on native species, ecosystem function, and ecosystem services. 3) Outreach and education efforts must be increased, both specifically toward lionfish and more generally toward the aquarium trade as a method of fish introductions. 4) Additional regulation should be considered to reduce the frequency of marine fish introduction into U.S. waters. However, the issue is more complicated than simply limiting the import of non-native species, and these complexities need to be considered simultaneously. 5) Health care providers along the east coast of the United States need to be notified that a venomous fish is now resident along the southeast United States. The introduction and spread of lionfish illustrates the difficulty inherent in managing introduced species in marine systems. Introduced species often spread via natural mechanisms after the initial introduction. Efforts to control the introduction of marine fish will fail if managers do not consider the natural dispersal of a species following an introduction. Thus, management strategies limiting marine fish introductions need to be applied over the scale of natural ecological dispersal to be effective, pointing to the need for a regional management approach defined by natural processes not by political boundaries. The introduction and success of lionfish along the east coast should change the long-held perception that marine fish invasions are a minimal threat to marine ecosystems. Research is needed to determine the effects of specific invasive fish species in specific ecosystems. More broadly, a cohesive plan is needed to manage, mitigate and minimize the effects of marine invasive fish species on ecosystems that are already compromised by other human activities. Presently, the magnitude of marine fish introductions as a stressor on marine ecosystems cannot be quantified, but can no longer be dismissed as negligible. (PDF contains 31 pages

Tumor microenvironment: becoming sick of Myc

Several years ago, we described Myc as “the oncogene from hell”, since evidence had just emerged that Myc, aside from being responsible for cell-cycle progression and tumor expansion, was also able to induce genomic instability in culture, wreaking havoc in tumor cells and accelerating tumor progression (Soucek and Evan, Cancer Cell 1:406–408, 2002; Vafa et al., Mol Cell 9:1031–1044, 2002). In this review, we discuss recent publications that expand Myc’s evil armory to include coordination of the crosstalk between tumor and microenvironment. Indeed, endogenous Myc, acting as a client for upstream oncogenic lesions, instructs the tumor stroma, engages a complex inflammatory response and induces angiogenesis, thus allowing the tumor to thrive. This is highly topical in light of the fact that Hanahan and Weinberg have recently redefined the hallmarks of cancer and pointed out that genomic instability and inflammation are essential for both their acquisition and development (Hanahan and Weinberg, Cell 144:646–674, 2011). Myc, it seems, is behind it all

The long journey to bring a Myc inhibitor to the clinic

Whitfield and Soucek discuss decades of research and a vast array of strategies that are finally yielding clinical trials for Myc inhibitors in cancer. The oncogene Myc is deregulated in the majority of human tumors and drives numerous hallmarks of cancer. Despite its indisputable role in cancer development and maintenance, Myc is still undrugged. Developing a clinical inhibitor for Myc has been particularly challenging owing to its intrinsically disordered nature and lack of a binding pocket, coupled with concerns regarding potentially deleterious side effects in normal proliferating tissues. However, major breakthroughs in the development of Myc inhibitors have arisen in the last couple of years. Notably, the direct Myc inhibitor that we developed has just entered clinical trials. Celebrating this milestone, with this Perspective, we pay homage to the different strategies developed so far against Myc and all of the researchers focused on developing treatments for a target long deemed undruggable

Familiarity with and preferences for oral and long-acting injectable HIV pre-exposure prophylaxis (PrEP) in a national sample of gay and bisexual men in the U.S.

Objectives: We sought to determine preferences for oral versus long-acting injectable (LAI) PrEP among gay and bisexual men (GBM). Methods: We surveyed a national U.S. sample of 1,071 GBM about forms of PrEP. Results: Overall, 46.0% preferred LAI, 14.3% oral, 21.7% whichever was most effective, 10.1% had no preference, and 7.8% would not take PrEP. There were no differences in PrEP preferences by race/ethnicity, income, region of residence, or relationship status. Those unwilling to take PrEP were significantly older than those who preferred LAI PrEP and those who would take either. Those who preferred the most effective form were younger, had less education, and reported more recent club drug use. Those who reported condomless anal sex and those who thought they were good PrEP candidates were more willing to take PrEP. Long-term health and side effects were of the greatest concern for both LAI and oral PrEP. Conclusions: The availability of LAI PrEP has the potential to increase uptake among GBM. The results of ongoing clinical trials of LAI PrEP will need to demonstrate similar or greater efficacy as daily Truvada for uptake to be maximized

Changes in familiarity with and willingness to take PrEP in a longitudinal study of highly sexually active gay and bisexual men

PURPOSE: For gay and bisexual men (GBM), research suggests that familiarity with Pre-Exposure Prophylaxis (PrEP) has been increasing since being approved by the U.S. FDA in 2012. However, it is less clear how willingness to start using PrEP has changed over time. Likewise, some have expressed concerns regarding the potential for risk compensation (i.e., reduced condom use) were one to start PrEP; however, again, it is unclear how these may have been changing over time. METHODS: We conducted baseline and 12 month assessments with 158 highly sexually active HIV-negative GBM in NYC who were assessed between 2011 and 2014. We examined change over time both between participants (based on when they entered the study), as well as within each participant (over the 12 months of his involvement). RESULTS: Familiarity with PrEP increased over time (both between and within participants); however, willingness to take PrEP did not change (neither between nor within participants). Few men believed taking PrEP would cause their condomless anal sex (CAS) to increase and this did not change over time. However, a majority believed PrEP would increase temptation for CAS, and this did not change over time within participants. Sexual compulsivity (SC) symptomology was associated with higher willingness to take PrEP and perceiving that PrEP would increase one’s temptations for CAS. Furthermore, recent CAS was associated with greater willingness to take PrEP, a perception that PrEP would increase one’s likelihood to engage in CAS, and a perception that being on PrEP would increase one’s temptation for CAS. CONCLUSIONS: Participants became more familiar with PrEP over time; however, willingness to start PrEP did not change, and this may serve as an opportunity for providers to 3 discuss PrEP with their patients. Higher risk men were interested in PrEP and pre-existing patterns of sexual behavior may be the primary determinant of CAS while on PrEP

Strategies to Inhibit Myc and Their Clinical Applicability

Myc is an oncogene deregulated in most-perhaps all-human cancers. Each Myc family member, c-, L-, and N-Myc, has been connected to tumor progression and maintenance. Myc is recognized as a "most wanted" target for cancer therapy, but has for many years been considered undruggable, mainly due to its nuclear localization, lack of a defined ligand binding site, and physiological function essential to the maintenance of normal tissues. The challenge of identifying a pharmacophore capable of overcoming these hurdles is reflected in the current absence of a clinically-viable Myc inhibitor. The first attempts to inhibit Myc used antisense technology some three decades ago, followed by small molecule inhibitors discovered through "classical" compound library screens. Notable breakthroughs proving the feasibility of systemic Myc inhibition were made with the Myc dominant negative mutant Omomyc, showing both the great promise in targeting this infamous oncogene for cancer treatment as well as allaying fears about the deleterious side effects that Myc inhibition might have on normal proliferating tissues. During this time many other strategies have appeared in an attempt to drug the undruggable, including direct and indirect targeting, knockdown, protein/protein and DNA interaction inhibitors, and translation and expression regulation. The inhibitors range from traditional small molecules to natural chemicals, to RNA and antisense, to peptides and miniproteins. Here, we briefly describe the many approaches taken so far, with a particular focus on their potential clinical applicability

Novel lung imaging biomarkers and skin gene expression subsetting in dasatinib treatment of systemic sclerosis-associated interstitial lung disease.

BackgroundThere are no effective treatments or validated clinical response markers in systemic sclerosis (SSc). We assessed imaging biomarkers and performed gene expression profiling in a single-arm open-label clinical trial of tyrosine kinase inhibitor dasatinib in patients with SSc-associated interstitial lung disease (SSc-ILD).MethodsPrimary objectives were safety and pharmacokinetics. Secondary outcomes included clinical assessments, quantitative high-resolution computed tomography (HRCT) of the chest, serum biomarker assays and skin biopsy-based gene expression subset assignments. Clinical response was defined as decrease of >5 or >20% from baseline in the modified Rodnan Skin Score (MRSS). Pulmonary function was assessed at baseline and day 169.ResultsDasatinib was well-tolerated in 31 patients receiving drug for a median of nine months. No significant changes in clinical assessments or serum biomarkers were seen at six months. By quantitative HRCT, 65% of patients showed no progression of lung fibrosis, and 39% showed no progression of total ILD. Among 12 subjects with available baseline and post-treatment skin biopsies, three were improvers and nine were non-improvers. Improvers mapped to the fibroproliferative or normal-like subsets, while seven out of nine non-improvers were in the inflammatory subset (p = 0.0455). Improvers showed stability in forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), while both measures showed a decline in non-improvers (p = 0.1289 and p = 0.0195, respectively). Inflammatory gene expression subset was associated with higher baseline HRCT score (p = 0.0556). Non-improvers showed significant increase in lung fibrosis (p = 0.0313).ConclusionsIn patients with SSc-ILD dasatinib treatment was associated with acceptable safety profile but no significant clinical efficacy. Patients in the inflammatory gene expression subset showed increase in skin fibrosis, decreasing pulmonary function and worsening lung fibrosis during the study. These findings suggest that target tissue-specific gene expression analyses can help match patients and therapeutic interventions in heterogeneous diseases such as SSc, and quantitative HRCT is useful for assessing clinical outcomes.Trial registrationClinicaltrials.gov NCT00764309

Concerted reductive coupling of an alkyl chloride at Pt(IV)

Oxidation of a doubly cyclometallated platinum(II) complex results in two isomeric platinum(IV) complexes. Whereas the trans isomer is robust, being manipulable in air at room temperature, the cis isomer decomposes at −20 °C and above. Reductive coupling of an alkyl chloride at the cis isomer gives a new species which can be reoxidised. The independence of this coupling on additional halide rules out the reverse of an SN2 reaction, leaving a concerted process as the only sensible reaction pathway

Willingness to take PrEP and potential for risk compensation among highly sexually active gay and bisexual men

Once-daily Truvada (Emtricitabine/Tenofovir) as a method of pre-exposure prophylaxis (PrEP) is one of the most promising biomedical interventions to eliminate new HIV infections; however, uptake among gay, bisexual, and other men who have sex with men has been slow amidst growing concern in popular/social media that PrEP use will result in reduced condom use (i.e., risk compensation). We investigated demographic, behavioral, and psychosocial differences in willingness to use PrEP as well as the perceived impact of PrEP on participants’ condom use in a sample of 206 highly sexually active HIV-negative gay and bisexual men. Nearly half (46.1%) said they would be willing to take PrEP if it were provided at no cost. Although men willing to take PrEP (vs. others) reported similar numbers of recent casual male partners (\u3c 6 weeks), they had higher odds of recent receptive condomless anal sex (CAS)—i.e., those already at high risk of contracting HIV were more willing to take PrEP. Neither age, race/ethnicity, nor income were associated with willingness to take PrEP, suggesting equal acceptability among subpopulations that are experiencing disparities in HIV incidence. There was limited evidence to suggest men would risk compensate. Only 10% of men who had not engaged in recent CAS felt that PrEP would result in them starting to have CAS. Men who had not tested for HIV recently were also significantly more likely than others to indicate willingness to take PrEP. Offering PrEP to men who test infrequently may serve to engage them more in routine HIV/STI testing and create a continued dialogue around sexual health between patient and provider in order to prevent HIV infection