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Still a Hard-to-Reach Population? Using Social Media to Recruit Latino Gay Couples for an HIV Intervention Adaptation Study
Online social networking use has increased rapidly among African American and Latino men who have sex with men (MSM), making it important to understand how these technologies can be used to reach, retain, and maintain individuals in care and promote health wellness. In particular, the Internet is increasingly recognized as a platform for health communication and education. However, little is known about how primarily Spanish-speaking populations use and engage with each other through social media platforms.
We aimed to recruit eligible couples for a study to adapt \"Connect 'n Unite\" (an HIV prevention intervention initially created for black gay couples) for Spanish-speaking Latino gay couples living in New York City.
In order to successfully design and implement an effective social media recruitment campaign to reach Spanish-speaking Latino gay couples for our ongoing \"Latinos en Pareja\" study, our community stakeholders and research team used McGuire's communication/persuasion matrix. The matrix guided our research, specifically each marketing \"channel\", targeted \"message\", and target population or \"receiver\". We developed a social media recruitment protocol and trained our research staff and stakeholders to conduct social media recruitment.
As a result, in just 1 month, we recruited all of our subjects (N=14 couples, that is, N=28 participants) and reached more than 35,658 participants through different channels. One of the major successes of our social media recruitment campaign was to build a strong stakeholder base that became involved early on in all aspects of the research process-from pilot study writing and development to recruitment and retention. In addition, the variety of \"messages\" used across different social media platforms (including Facebook, the \"Latinos en Pareja\" study website, Craigslist, and various smartphone applications such as Grindr, SCRUFF, and Jack'd) helped recruit Latino gay couples. We also relied on a wide range of community-based organizations across New York City to promote the study and build in the social media components.
Our findings highlight the importance of incorporating communication technologies into the recruitment and engagement of participants in HIV interventions. Particularly, the success of our social media recruitment strategy with Spanish-speaking Latino MSM shows that this population is not particularly \"hard to reach\", as it is often characterized within public health literature.
Journal Article
Ecosystem bioelement variability is associated with freshwater animal aggregations at the aquatic-terrestrial interface
The impacts of animals on the biogeochemical cycles of major bioelements like C, N, and P are well-studied across ecosystem types. However, more than 20 elements are necessary for life. The feedbacks between animals and the biogeochemical cycles of the other bioelements are an emerging research priority. We explored how much freshwater mussels (Bivalvia: Unionoida) were related to variability in ecosystem pools of 10 bioelements (Ca, Cu, Fe, K, Mn, Na, Mg, P, S and Zn) in streams containing a natural mussel density gradient in the US Interior Highlands. We studied the concentrations of these bioelements across the aquatic-terrestrial interface—in the porewater of riverine gravel bars, and the emergent macrophyte Justicia americana. Higher mussel density was associated with increased calcium in gravel bars and macrophytes. Mussel density also correlated with variability in iron and other redox-sensitive trace elements in gravel bars and macrophytes, although this relationship was mediated by sediment grain size. We found that two explanations for the patterns we observed are worthy of further research: (1) increased calcium availability in gravel bars near denser mussel aggregations may be a product of the buildup and dissolution of shells in the gravel bar, and (2) mussels may alter redox conditions, and thus elemental availability in gravel bars with fine sediments, either behaviorally or through physical structure provided by shell material. A better understanding of the physical and biogeochemical impacts of animals on a wide range of elemental cycles is thus necessary to conserve the societal value of freshwater ecosystems.
Journal Article
Bevacizumab, olaparib, and durvalumab in patients with relapsed ovarian cancer: a phase II clinical trial from the GINECO group
Most patients with advanced ovarian cancer (AOC) ultimately relapse after platinum-based chemotherapy. Combining bevacizumab, olaparib, and durvalumab likely drives synergistic activity. This open-label phase 2 study (NCT04015739) aimed to assess activity and safety of this triple combination in female patients with relapsed high-grade AOC following prior platinum-based therapy. Patients were treated with olaparib (300 mg orally, twice daily), the bevacizumab biosimilar FKB238 (15 mg/kg intravenously, once-every-3-weeks), and durvalumab (1.12 g intravenously, once-every-3-weeks) in nine French centers. The primary endpoint was the non-progression rate at 3 months for platinum-resistant relapse or 6 months for platinum-sensitive relapse per RECIST 1.1 and irRECIST. Secondary endpoints were CA-125 decline with CA-125 ELIMination rate constant K (KELIM-B) per CA-125 longitudinal kinetics over 100 days, progression free survival and overall survival, tumor response, and safety. Non-progression rates were 69.8% (90%CI 55.9%-80.0%) at 3 months for platinum-resistant relapse patients (N = 41), meeting the prespecified endpoint, and 43.8% (90%CI 29.0%-57.4%) at 6 months for platinum-sensitive relapse (N = 33), not meeting the prespecified endpoint. Median progression-free survival was 4.1 months (95%CI 3.5–5.9) and 4.9 months (95%CI 2.9–7.0) respectively. Favorable KELIM-B was associated with better survival. No toxic deaths or major safety signals were observed. Here we show that further investigation of this triple combination may be considered in AOC patients with platinum-resistant relapse.
Prognosis for patients diagnosed with advanced stage ovarian cancer remains poor. Here the authors report the results of a phase 2 study of a triple combination of the PARP inhibitor olaparib in combination with durvalumab (anti-PD1) and bevacizumab (antiVEGF) in advanced ovarian cancer.
Journal Article
Sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer
Neuronal nerve processes in the tumor microenvironment were highlighted recently. However, the origin of intra-tumoral nerves remains poorly known, in part because of technical difficulties in tracing nerve fibers via conventional histological preparations. Here, we employ three-dimensional (3D) imaging of cleared tissues for a comprehensive analysis of sympathetic innervation in a murine model of pancreatic ductal adenocarcinoma (PDAC). Our results support two independent, but coexisting, mechanisms: passive engulfment of pre-existing sympathetic nerves within tumors plus an active, localized sprouting of axon terminals into non-neoplastic lesions and tumor periphery. Ablation of the innervating sympathetic nerves increases tumor growth and spread. This effect is explained by the observation that sympathectomy increases intratumoral CD163
+
macrophage numbers, which contribute to the worse outcome. Altogether, our findings provide insights into the mechanisms by which the sympathetic nervous system exerts cancer-protective properties in a mouse model of PDAC.
The autonomic nervous systems densely innervate the pancreas, but its contribution to pancreatic ductal adenocarcinoma (PDAC) progression is not fully understood. Here, the authors characterize the pattern of sympathetic innervation by 3D imaging in a murine model of PDAC and show that sympathectomy aggravates cancer progression.
Journal Article
The apoptosis inhibitor Bcl-xL controls breast cancer cell migration through mitochondria-dependent reactive oxygen species production
The Bcl-xL apoptosis inhibitor plays a major role in vertebrate development. In addition to its effect on apoptosis, Bcl-xL is also involved in cell migration and mitochondrial metabolism. These effects may favour the onset and dissemination of metastasis. However, the underlying molecular mechanisms remain to be fully understood. Here we focus on the control of cell migration by Bcl-xL in the context of breast cancer cells. We show that Bcl-xL silencing led to migration defects in Hs578T and MDA-MB231 cells. These defects were rescued by re-expressing mitochondria-addressed, but not endoplasmic reticulum-addressed, Bcl-xL. The use of BH3 mimetics, such as ABT-737 and WEHI-539 confirmed that the effect of Bcl-xL on migration did not depend on interactions with BH3-containing death accelerators such as Bax or BH3-only proteins. In contrast, the use of a BH4 peptide that disrupts the Bcl-xL/VDAC1 complex supports that Bcl-xL by acting on VDAC1 permeability contributes to cell migration through the promotion of reactive oxygen species production by the electron transport chain. Collectively our data highlight the key role of Bcl-xL at the interface between cell metabolism, cell death, and cell migration, thus exposing the VDAC1/Bcl-xL interaction as a promising target for anti-tumour therapy in the context of metastatic breast cancer.
Journal Article
Animal aggregations promote emergent aquatic plant production at the aquatic–terrestrial interface
The roles mobile animals and abiotic processes play as vectors for resource transfers between ecosystems (“subsidies”) are well studied, but the idea that resources from animals with limited mobility may be transported across boundaries through intermediate taxa remains unexplored. Aquatic plants (“macrophytes”) are globally distributed and may mediate transfers of aquatic-derived nutrients from aggregations of aquatic animals to terrestrial ecosystems when consumed by terrestrial herbivores. We used mesocosms (94 × 44 cm) to test whether aquatic animal-generated biogeochemical hotspots increase growth and nutrient content in macrophytes using the macrophyte Justicia americana and freshwater mussels. Justicia americana biomass production increased and belowground biomass allocation changed with increasing mussel density. At high mussel density, water-column phosphorus increased and carbon: phosphorus ratios in J. americana tissues decreased. We deployed motion-sensing cameras to explore herbivory on J. americana growing along the margins of the Kiamichi River, Oklahoma, and documented feeding by large mammals (Odocoileus virginianus, Sus scrofa, and Bos taurus). Thus, biogeochemical hotspots generated by aquatic animal aggregations can promote macrophyte production that subsequently is transferred to terrestrial animals. More broadly, this suggests that reductions in aquatic animal biomass may have bottom-up impacts that indirectly affect terrestrial ecosystems via plant–animal interactions bridging ecosystem boundaries.
Journal Article
Non-invasive prediction of recurrence in bladder cancer by detecting somatic TERT promoter mutations in urine
Background:
Urothelial bladder cancer (UBC) is characterised by a high risk of recurrence. Patient monitoring is currently based on iterative cystoscopy and on urine cytology with low sensitivity in non-muscle-invasive bladder cancer (NMIBC). Telomerase reverse transcriptase (TERT) is frequently reactivated in UBC by promoter mutations.
Methods:
We studied whether detection of TERT mutation in urine could be a predictor of UBC recurrence and compared this to cytology/cystoscopy for patient follow-up. A total of 348 patients treated by transurethral bladder resection for UBC were included together with 167 control patients.
Results:
Overall sensitivity was 80.5% and specificity 89.8%, and was not greatly impacted by inflammation or infection. TERT remaining positive after initial surgery was associated with residual carcinoma
in situ
. TERT in urine was a reliable and dynamic predictor of recurrence in NMIBC (
P
<0.0001). In univariate analysis, TERT positive-status after initial surgery increased risk of recurrence by 5.34-fold (
P
=0.0004). TERT positive-status was still associated with recurrence in the subset of patients with negative cystoscopy (
P
=0.034).
Conclusions:
TERT mutations in urine might be helpful for early detection of recurrence in UBC, especially in NMIBC.
Journal Article
An apical protein, Pcr2, is required for persistent movement by the human parasite Toxoplasma gondii
The phylum Apicomplexa includes thousands of species of unicellular parasites that cause a wide range of human and animal diseases such as malaria and toxoplasmosis. To infect, the parasite must first initiate active movement to disseminate through tissue and invade into a host cell, and then cease moving once inside. The parasite moves by gliding on a surface, propelled by an internal cortical actomyosin-based motility apparatus. One of the most effective invaders in Apicomplexa is Toxoplasma gondii , which can infect any nucleated cell and any warm-blooded animal. During invasion, the parasite first makes contact with the host cell \"head-on\" with the apical complex, which features an elaborate cytoskeletal apparatus and associated structures. Here we report the identification and characterization of a new component of the apical complex, Preconoidal region protein 2 (Pcr2). Pcr2 knockout parasites replicate normally, but they are severely diminished in their capacity for host tissue destruction due to significantly impaired invasion and egress, two vital steps in the lytic cycle. When stimulated for calcium-induced egress, Pcr2 knockout parasites become active, and secrete effectors to lyse the host cell. Calcium-induced secretion of the major adhesin, MIC2, also appears to be normal. However, the movement of the Pcr2 knockout parasite is spasmodic, which drastically compromises egress. In addition to faulty motility, the ability of the Pcr2 knockout parasite to assemble the moving junction is impaired. Both defects likely contribute to the poor efficiency of invasion. Interestingly, actomyosin activity, as indicated by the motion of mEmerald tagged actin chromobody, appears to be largely unperturbed by the loss of Pcr2, raising the possibility that Pcr2 may act downstream of or in parallel with the actomyosin machinery.
Journal Article
BRD4-mediated repression of p53 is a target for combination therapy in AML
Acute myeloid leukemia (AML) is a typically lethal molecularly heterogeneous disease, with few broad-spectrum therapeutic targets. Unusually, most AML retain wild-type
TP53
, encoding the pro-apoptotic tumor suppressor p53. MDM2 inhibitors (MDM2i), which activate wild-type p53, and BET inhibitors (BETi), targeting the BET-family co-activator BRD4, both show encouraging pre-clinical activity, but limited clinical activity as single agents. Here, we report enhanced toxicity of combined MDM2i and BETi towards AML cell lines, primary human blasts and mouse models, resulting from BETi’s ability to evict an unexpected repressive form of BRD4 from p53 target genes, and hence potentiate MDM2i-induced p53 activation. These results indicate that wild-type
TP53
and a transcriptional repressor function of BRD4 together represent a potential broad-spectrum synthetic therapeutic vulnerability for AML.
MDM2 and BET inhibitors have shown efficacy in AML treatment. Here, the authors show that the two compounds can synergize through both p53 protein stabilization and inhibition of BRD4-mediated repression of p53 target genes.
Journal Article