Urbanization comprehensively impairs biological rhythms in coral holobionts

Coral reefs are in global decline due to climate change and anthropogenic influences (Hughes et al., Conservation Biology, 27: 261–269, 2013). Near coastal cities or other densely populated areas, coral reefs face a range of additional challenges. While considerable progress has been made in understanding coral responses to acute individual stressors (Dominoni et al., Nature Ecology & Evolution, 4: 502–511, 2020), the impacts of chronic exposure to varying combinations of sensory pollutants are largely unknown. To investigate the impacts of urban proximity on corals, we conducted a year-long in-natura study—incorporating sampling at diel, monthly, and seasonal time points—in which we compared corals from an urban area to corals from a proximal non-urban area. Here we reveal that despite appearing relatively healthy, natural biorhythms and environmental sensory systems were extensively disturbed in corals from the urban environment. Transcriptomic data indicated poor symbiont performance, disturbance to gametogenic cycles, and loss or shifted seasonality of vital biological processes. Altered seasonality patterns were also observed in the microbiomes of the urban coral population, signifying the impact of urbanization on the holobiont, rather than the coral host alone. These results should raise alarm regarding the largely unknown long-term impacts of sensory pollution on the resilience and survival of coral reefs close to coastal communities

Perspectives and Update on the Global Shortage of Verteporfin (Visudyne®)

An ongoing global shortage of verteporfin (Visudyne®) limits the treatment possibilities for several chorioretinal diseases, including central serous chorioretinopathy, choroidal hemangioma, and polypoidal choroidal vasculopathy. Verteporfin is required to perform photodynamic therapy in these ocular diseases. Therefore, the current situation has a substantial impact on eye care worldwide. The worldwide supply of verteporfin appears to be manufactured by a single factory, which is situated in the United States. The distribution of verteporfin is done by different companies for different regions of the world. Official communication on the shortage by the responsible companies has been scarce and over the past years several promises with regards to resolution of the shortage have not been fulfilled. The delivery of new batches of verteporfin is at irregular intervals, unpredictable, and may not be fairly balanced between different regions or countries in the world. To ensure a fair distribution of available verteporfin within a country, several measures can be taken. In the Netherlands, a national committee, consisting of ophthalmologists, is in place to arrange this. On the European level, the European Union and European Medicine Agency have plans to monitor medicine shortages more closely and to intervene if necessary. With a more intensified monitoring and regulation of medicine supplies, future impending shortages may be prevented. Remarkably, the amount of medicine shortages is increasing, having a significant and sometimes irreversible impact on patient care. Thus, efforts should be undertaken to minimize the consequences and, whenever possible, to prevent future medicine shortages

Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer

BACKGROUND Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer. METHODS In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2: 1 ratio to receive niraparib (300 mg) or placebo once daily. The primary end point was progression-free survival. RESULTS Of 553 enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234 assigned to niraparib and 116 to placebo). Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval [CI], 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61; P < 0.001 for all three comparisons). The most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications. CONCLUSIONS Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274.)Tesaro; Amgen; Genentech; Roche; AstraZeneca; Myriad Genetics; Merck; Gradalis; Cerulean; Vermillion; ImmunoGen; Pfizer; Bayer; Nu-Cana BioMed; INSYS Therapeutics; GlaxoSmithKline; Verastem; Mateon Therapeutics; Pharmaceutical Product Development; Clovis Oncology; Janssen/Johnson Johnson; Eli Lilly; Merck Sharp DohmeThis article was published on October 8, 2016; 6 Month Embargo.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Untangling the molecular basis of coral response to sedimentation

10.1111/mec.16263Molecular Ecology1-1

The Risk of Rectal Temperature Measurement in Neutropenia

Background: Avoiding rectal thermometry is recommended in patients with neutropenic fever. Permeability of the anal mucosa may result in a higher risk of bacteremia in these patients. Still, this recommendation is based on only a few studies. Methods: This retrospective study included all individuals admitted to our emergency department during 2014–2017 with afebrile (body temperature <38.3°C) neutropenia (neutrophil count <500 cells/microL) who were over the age of 18. Patients were stratified by the presence or absence of a rectal temperature measurement. The primary outcome was bacteremia during the first five days of index hospitalization; the secondary outcome was in-hospital mortality. Results: The study included 40 patients with rectal temperature measurements and 407 patients whose temperatures were only measured orally. Among patients with oral temperature measurements, 10.6% had bacteremia, compared to 5.1% among patients who had rectal temperature measurements. Rectal temperature measurement was not associated with bacteremia, neither in non-matched (odds ratio [OR] 0.36, 95% confidence interval [CI] 0.07–1.77) nor in matched cohort analyses (OR 0.37, 95% CI 0.04–3.29). In-hospital mortality was also similar between the groups. Conclusions: Patients with neutropenia who had their temperature taken using a rectal thermometer did not experience a higher frequency of events of documented bacteremia or increased in-hospital mortality

Bacterial lifestyle switch in response to algal metabolites

Unicellular algae, termed phytoplankton, greatly impact the marine environment by serving as the basis of marine food webs and by playing central roles in the biogeochemical cycling of elements. The interactions between phytoplankton and heterotrophic bacteria affect the fitness of both partners. It is becoming increasingly recognized that metabolic exchange determines the nature of such interactions, but the underlying molecular mechanisms remain underexplored. Here, we investigated the molecular and metabolic basis for the bacterial lifestyle switch, from coexistence to pathogenicity, in Sulfitobacter D7 during its interaction with Emiliania huxleyi, a cosmopolitan bloom-forming phytoplankter. To unravel the bacterial lifestyle switch, we analyzed bacterial transcriptomes in response to exudates derived from algae in exponential growth and stationary phase, which supported the Sulfitobacter D7 coexistence and pathogenicity lifestyles, respectively. In pathogenic mode, Sulfitobacter D7 upregulated flagellar motility and diverse transport systems, presumably to maximize assimilation of E. huxleyi-derived metabolites released by algal cells upon cell death. Algal dimethylsulfoniopropionate (DMSP) was a pivotal signaling molecule that mediated the transition between the lifestyles, supporting our previous findings. However, the coexisting and pathogenic lifestyles were evident only in the presence of additional algal metabolites. Specifically, we discovered that algae-produced benzoate promoted the growth of Sulfitobacter D7 and hindered the DMSP-induced lifestyle switch to pathogenicity, demonstrating that benzoate is important for maintaining the coexistence of algae and bacteria. We propose that bacteria can sense the physiological state of the algal host through changes in the metabolic composition, which will determine the bacterial lifestyle during interaction.ISSN:2050-084

Urbanization comprehensively impairs biological rhythms in coral holobionts

Coral reefs are in global decline due to climate change and anthropogenic influences (Hughes et al., Conservation Biology, 27: 261-269, 2013). Near coastal cities or other densely populated areas, coral reefs face a range of additional challenges. While considerable progress has been made in understanding coral responses to acute individual stressors (Dominoni et al., Nature Ecology & Evolution, 4: 502-511, 2020), the impacts of chronic exposure to varying combinations of sensory pollutants are largely unknown. To investigate the impacts of urban proximity on corals, we conducted a year-long in-natura study-incorporating sampling at diel, monthly, and seasonal time points-in which we compared corals from an urban area to corals from a proximal non-urban area. Here we reveal that despite appearing relatively healthy, natural biorhythms and environmental sensory systems were extensively disturbed in corals from the urban environment. Transcriptomic data indicated poor symbiont performance, disturbance to gametogenic cycles, and loss or shifted seasonality of vital biological processes. Altered seasonality patterns were also observed in the microbiomes of the urban coral population, signifying the impact of urbanization on the holobiont, rather than the coral host alone. These results should raise alarm regarding the largely unknown long-term impacts of sensory pollution on the resilience and survival of coral reefs close to coastal communities.publishe

Developing A Broadly Protective MRNA Influenza Vaccine: A Review

Gemstone Team MUTATECurrent influenza vaccines are limited in their efficacy due to antigenic drift of the hemagglutinin target; advances in mRNA vaccines in response to the COVID-19 pandemic may provide a new direction for influenza vaccine development. Existing literature shows that mRNA vaccines have higher efficacy in preventing illness, hospitalizations, and death. We evaluated eleven influenza A viral proteins as potential targets for an mRNA vaccine under the following criteria: degree of conservation, ability to elicit a robust immune response, and ability to prevent illness and death. We recommend future researchers direct their efforts towards developing an annually administered tri-sequence mRNA vaccine targeting hemagglutinin head (HA1), the matrix 2 ectodomain (M2e), and nucleoprotein (NP). Development of a highly effective influenza mRNA vaccine would be significant for prevention of disease burden worldwide