Evidence of microplastics from benthic jellyfish (Cassiopea xamachana) in Florida estuaries.

Plastic pollution is a concern in many nearshore ecosystems, and it is critical to understand how microplastics (plastics <5 mm in length) affect nearshore marine biota. Here, we report the presence of microplastics in the benthic, upside-down jellyfish (Cassiopea xamachana) across three estuaries in south Florida. Microplastics were recovered from Cassiopea using an acid digestion, then enumerated via microscopy, and identified using micro Fourier-transform interferometer (µFTIR) analysis. Out of 115 specimens analyzed, 77% contained microplastics. Bell diameter and number of plastics per individual varied significantly across locations with the highest plastic densities and bell diameter observed in individuals from Big Pine Key, followed by Jupiter, and Sarasota. µFTIR analysis confirmed that synthetic microfibers were the dominant microplastic measured at all three locations and may indicate Cassiopea as potential sinks of microplastic. Cassiopea may be used as bioindicators of microplastic contamination in the future, allowing for potential plastic pollution mitigation.

Effects of chronic pesticide exposure on an epibenthic oyster reef community.

In recent decades, oyster reefs have been deteriorating throughout North America as a result of multiple interacting anthropogenic stressors, including pesticide pollution. Here we elucidated the potential chronic effects of the commonly utilized pesticide, carbaryl, on oyster reef communities in the Loxahatchee River Estuary in southeast Florida. Though carbaryl had a limited effect on total epifaunal community diversity, species richness and evenness, the results of this experiment indicate that carbaryl significantly shifted crustacean community composition, resulting in a substantial loss in total crustacean abundance. One crustacean in particular, Americorophium spp. (tube building amphipod), was significantly less abundant within the carbaryl treatment, driving the shift in crustacean community composition. Ultimately, our results signal that pesticide pollution in estuaries will negatively impact crustaceans. Over time, this may shift benthic community composition, potentially disrupting species interactions and threatening valuable economic and ecosystem services.

Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency.

OBJECTIVE: Pro-opiomelanocortin (POMC)-derived peptides act on neurons expressing the Melanocortin 4 receptor (MC4R) to reduce body weight. Setmelanotide is a highly potent MC4R agonist that leads to weight loss in diet-induced obese animals and in obese individuals with complete POMC deficiency. While POMC deficiency is very rare, 1-5% of severely obese individuals harbor heterozygous mutations in MC4R. We sought to assess the efficacy of Setmelanotide in human MC4R deficiency. METHODS: We studied the effects of Setmelanotide on mutant MC4Rs in cells and the weight loss response to Setmelanotide administration in rodent studies and a human clinical trial. We annotated the functional status of 369 published MC4R variants. RESULTS: In cells, we showed that Setmelanotide is significantly more potent at MC4R than the endogenous ligand alpha-melanocyte stimulating hormone and can disproportionally rescue signaling by a subset of severely impaired MC4R mutants. Wild-type rodents appear more sensitive to Setmelanotide when compared to MC4R heterozygous deficient mice, while MC4R knockout mice fail to respond. In a 28-day Phase 1b clinical trial, Setmelanotide led to weight loss in obese MC4R variant carriers. Patients with POMC defects upstream of MC4R show significantly more weight loss with Setmelanotide than MC4R deficient patients or obese controls. CONCLUSIONS: Setmelanotide led to weight loss in obese people with MC4R deficiency; however, further studies are justified to establish whether Setmelanotide can elicit clinically meaningful weight loss in a subset of the MC4R deficient obese population.

Relamorelin Reduces Vomiting Frequency and Severity and Accelerates Gastric Emptying in Adults With Diabetic Gastroparesis.

BACKGROUND & AIMS: Gastroparesis is an important complication of diabetes. We investigated the effects of relamorelin (a pentapeptide-selective agonist of the ghrelin receptor that speeds gastric emptying in patients with diabetes) in patients with diabetic gastroparesis. METHODS: We performed a double-blind trial of 204 patients (78% Caucasian; 67% female; mean age, 55 y; 88% with type 2 diabetes) with diabetic gastroparesis with moderate to severe symptoms and delayed gastric emptying at 27 clinical centers, from June 2012 until August 2013. Patients were assigned randomly (1:1:1) to groups given placebo or subcutaneous relamorelin 10 µg once or twice daily. The primary end point was the half-time of gastric emptying. Secondary end points included nausea, abdominal pain, bloating, early satiety, as well as the composite score of these 4 subjective symptoms and vomiting frequency and severity. RESULTS: Twice-daily relamorelin significantly accelerated gastric emptying (P < .03) and reduced vomiting frequency (by ∼60%) and severity vs placebo (P ≤ .033). Compared with placebo, relamorelin did not improve other gastrointestinal symptoms, such as abdominal pain and satiety. In the 119 patients (58.3%) with baseline vomiting, twice-daily relamorelin significantly reduced the half-time of gastric emptying and vomiting, as well as nausea, abdominal pain, bloating, and early satiety compared with placebo (composite score, P = .043). No overall safety concerns were identified. CONCLUSIONS: In a clinical trial of patients with diabetic gastroparesis, relamorelin (10 µg twice daily) significantly accelerated gastric emptying and significantly reduced vomiting, compared with placebo. Among patients with baseline vomiting, relamorelin had prokinetic effects and significantly reduced vomiting and also improved other symptoms of diabetic gastroparesis compared with placebo. ClincialTrials.gov number: NCT01571297.

Does landscape context mediate the nature of density dependence for a coral reef fish?

Over-harvest and landscape change are two of the greatest threats to marine ecosystems. Over-harvest may directly affect key population regulation mechanisms (e.g., density dependence), with the magnitude of the effects being further influenced by changes in landscape structure and associated resource availability. Because resource availability and conspecific density often co-vary within the natural landscape, manipulative experiments are needed to understand how changes in these two drivers may affect density dependence in wild populations. We used a common, shoaling, coral reef fish (white grunt, Haemulon plumierii) as our model species, and manipulated fish densities and landscape context of artificial reef habitats to assess the effects of each on fish condition. We found evidence of inverse density dependence, where individual condition was positively related to conspecific density; landscape context had little effect. Mean grunt condition on natural patch reefs was similar to that for our low grunt density treatment artificial reefs, possibly due to differences in fish densities or landscape context. These findings suggest that over-harvest may have detrimental effects on wild populations that extend beyond mere reductions in population size, especially for group-living species.

Thresholds of ecosystem response to nutrient enrichment from fish aggregations.

Biogeochemical hotspots can be driven by aggregations of animals, via excretion, that provide a concentrated source of limiting nutrients for primary producers. In a subtropical seagrass ecosystem, we characterized thresholds of ecological change associated with such hotspots surrounding artificial reef habitats. We deployed reefs of three sizes to aggregate fishes at different densities (and thus different levels of nutrient supply via excretion) and examined seagrass characteristics that reflect ecosystem processes. Responses varied as a function of reef size, with higher fish densities (on larger reefs) associated with more distinct ecological thresholds. For example, adjacent to larger reefs, the percentage of P content (%P) of seagrass (Thalassia testudinum) blades was significantly higher than background concentrations; fish densities on smaller reefs were insufficient to support sharp transitions in %P. Blade height was the only variable characterized by thresholds adjacent to smaller reefs, but lower fish densities (and hence, nutrient input) on smaller reefs were not sufficient for luxury nutrient storage by seagrass. Identifying such complexities in ecological thresholds is crucial for characterizing the extent to which biogeochemical hotspots may influence ecosystem function at a landscape scale.

Randomized controlled phase Ib study of ghrelin agonist, RM-131, in type 2 diabetic women with delayed gastric emptying: pharmacokinetics and pharmacodynamics.

OBJECTIVE: To investigate the pharmacokinetics (PK), pharmacodynamics, and safety of single-dose RM-131 in type 2 diabetic patients with gastrointestinal cardinal symptoms (GCSI) and previously documented delayed gastric emptying (DGE). RESEARCH DESIGN AND METHODS: In a randomized crossover study, 10 female patients received RM-131 (100 µg s.c.) or placebo and underwent scintigraphic gastric emptying (GE) and colonic filling at 6 h (CF6) of a solid-liquid meal administered 30 min postdosing. Adverse events, plasma glucose, and hormonal levels were assessed. GCSI daily diary (GCSI-DD) was completed during treatments. PK was assessed in this cohort and healthy volunteers (HVs). RESULTS: At screening, HbA(1c) was 7.2 ± 0.4% (SEM) and total GCSI-DD score was 1.32 ± 0.21. RM-131 accelerated GE t(1/2) of solids (P = 0.011); mean difference (Δ) in solid GE t(1/2) was 68.3 min (95% CI 20-117) or 66.1%. There were numerical differences in GE lag time, CF6 solids, and GE t(1/2) liquids (all P < 0.14). With a significant (P < 0.014) order effect, further analysis of the first treatment period (n = 5 per group) confirmed significant RM-131 effects on GE t(1/2) (solids, P = 0.016; liquids, P = 0.024; CF6, P = 0.013). PK was similar in DGE patients and HVs. There were increases in 120-min blood glucose (P = 0.07) as well as 30-90-min area under the curve (AUC) levels of growth hormone, cortisol, and prolactin (all P < 0.02) with single-dose RM-131. Only light-headedness was reported more on RM-131. CONCLUSIONS: RM-131 greatly accelerates the GE of solids in patients with type 2 diabetes and documented DGE. PK is similar in diabetic patients and HVs.

Effects of anthropogenic disturbance on the abundance and size of epibenthic jellyfish Cassiopea spp.

Jellyfish blooms in pelagic systems appear to be increasing on a global scale because of anthropogenic impacts, but much less is known about the link between human activities and epibenthic jellyfish abundance. The aim of this study was to investigate whether the epibenthic jellyfish, Cassiopea spp., were found in greater abundance, and attained larger sizes, in coastal habitats adjacent to high human population densities compared to sites adjacent to uninhabited areas on Abaco Island, Bahamas. Cassiopea spp. were found to be significantly more dense and larger in areas with high human population densities. Ambient nutrient levels and nutrient content of seagrass were elevated in high human population density sites, and may be one mechanism driving higher abundance and size of Cassiopea spp. Cassiopea spp. may have important effects on community structure and ecosystem function in critical coastal ecosystems (e.g., seagrass beds), and their impacts warrant further study.

Familial aggregation of bothersome benign prostatic hyperplasia symptoms.

OBJECTIVES: To evaluate familial aggregation and the mode of inheritance of bothersome benign prostatic hyperplasia (BPH). METHODS: During an extension of the North American Finasteride Trial, 301 of 895 patients and 158 spousal controls completed a family history questionnaire. Segregation analysis was performed to examine the mode of inheritance in first-degree relatives of the 301 probands. RESULTS: The lifetime cumulative probability of bothersome BPH was similar in relatives of those with BPH (0.35; 95% confidence interval [CI] 0.28 to 0.44) and spousal controls (0.36; 95% CI 0.22 to 0.56), but the age of onset was significantly earlier in relatives of cases than controls (P = 0.001). Fathers of those with BPH had a significantly elevated risk of bothersome BPH (unadjusted odds ratio [OR] 2.1; 95% CI 1.2 to 3.8) and brothers had a significantly elevated risk of both bothersome BPH (OR 3.5; 95% CI 1.7 to 7.3) and transurethral resection of the prostate (OR 3.6; 95% CI 1.4 to 8.8). After adjusting for family size, the risk of bothersome BPH increased approximately twofold with each additional affected first-degree relative (0 relatives, OR 1.0; 1 relative, OR 1.7; 2 relatives, OR 4.7). Segregation analysis suggested a rare autosomal codominant allele (frequency 0.0004). CONCLUSIONS: These findings confirm previous findings that family history and early age of onset are associated with an increased risk of BPH and that the most likely mode of inheritance is autosomal dominant or codominant. Bothersome BPH appears to have a weaker genetic component than more restrictive definitions of hereditary BPH. Thus, linkage studies are more likely to be successful if they focus on stricter definitions of hereditary BPH (eg, early onset, large volume, strong family history) rather than symptomatic or clinical BPH.

Long-term 6-year experience with finasteride in patients with benign prostatic hyperplasia.

OBJECTIVES: To summarize the 6-year clinical trial data with finasteride. Benign prostatic hyperplasia is a chronic and progressive disease and therefore assessment of long-term safety and efficacy is important. METHODS: The North American and International Phase III Finasteride trials enrolled symptomatic men with enlarged prostate glands. The initial 1-year placebo-controlled study was followed by a 5-year open-label extension. In total, 6-year finasteride data were available in 487 patients originally randomized to finasteride, and 5-year data were available on 238 patients originally randomized to placebo. RESULTS: After 6 years of treatment with finasteride 5 mg, the mean quasi-American Urological Association Symptom Score improved by 4.0 points, the median prostate volume decreased by 24%, and the mean maximal urinary flow rate increased by 2.9 mL/s (P <0.001 for all parameters). Long-term finasteride treatment was well tolerated, with a low incidence of drug-related sexual adverse events occurring during the first year and even fewer occurrences during the 5-year open extension. CONCLUSIONS: Treatment with finasteride leads to durable improvement in urinary tract symptoms, flow rate, and prostate volume, with no increase in the prevalence of drug-related adverse events over time.