Health-related quality of life in ethnically diverse Black prostate cancer survivors: a convergent parallel mixed-methods approach.

PURPOSE: This study examined the health-related quality of life (HRQoL) among ethnically diverse Black men (BM) with prostate cancer (CaP) in the United States. METHODS: A convergent parallel mixed-methods design, employing both qualitative and quantitative research, involved recruiting Black CaP survivors through multiple channels. The target population was native-born BM (NBBM), African-born BM (ABBM), and Caribbean-born BM (CBBM). QoL for all men was assessed using The Functional Assessment Cancer Therapy-Prostate (FACT-P) measure, which includes five domains: physical- (PWB), emotional- (EWB), social-(SWB), and functional-wellbeing (FWB), and a CaP subscale (PCS). A subset of men completed qualitative interviews. Demographic and clinical characteristics were also collected. RESULTS: Black CaP survivors aged 49-85 participated in the study (n = 108), with a subset (n = 31) completing a qualitative interview. Participants were mainly NBBM (72.2%) and treated with radiotherapy (51.9%). The FACT-P scale total mean score (± SD) was 114 ± 24.1 (theoretical range 0-156), with lower scores reported on the SWB, FWB, and EWB domains. The mixed-methods findings approach included meta-inferences derived from integrating the corresponding quantitative and qualitative data, covering all the domains within the FACT-P. CONCLUSION: Black CaP survivors experienced significant burdens that impacted their overall HRQoL. The analysis revealed impacts on physical, social, and emotional well-being, with variations among ethnic groups suggesting the need for culturally tailored interventions. EWB was also profoundly impacted by CaP treatment, with universal emotional burdens emphasized across all groups. Healthcare providers must recognize and address these multifaceted needs to promote better outcomes and HRQoL for Black CaP survivors.

Voices of Black men: reflecting on prostate cancer survivorship care plans.

PURPOSE: This study addresses the critical issue of survivorship care for Black prostate cancer survivors. The aim was to explore their awareness of survivorship care plans to improve prostate cancer care and survivorship within this high-risk group. METHODS: Utilizing a thematic analysis approach, we conducted in-depth interviews focused on analyzing post-treatment experiences of Black prostate cancer survivors by applying interpretive explanations to data collected from participants. RESULTS: Participants reported a significant gap in survivorship care plan communication post-treatment, as these plans were seldom discussed. Survivors highlighted the adoption of post-treatment strategies and self-education as means to enhance their comprehension of the survivorship process. Black survivors demonstrated an intrinsic motivation, after feeling "discarded," to find suitable resources to enhance their survivorship care for a better quality of life. CONCLUSION: The prioritization of post-treatment care for Black prostate cancer survivors is important. By offering comprehensive post-treatment education, improving symptom transparency, and establishing safe spaces for open discussion, the quality of life of Black survivors may be substantially improved. IMPLICATIONS FOR CANCER SURVIVORS: There is a pressing need for dynamic post-treatment care coordination tailored to Black prostate cancer survivors. A lack of crucial post-treatment education for this population that experiences disproportionate burden of prostate cancer may exacerbate cancer health disparities. Addressing this care coordination gap may improve support systems, survivor well-being, and better cancer outcomes.

Quality of life assessment among ethnically diverse Black prostate cancer survivors: a constructivist grounded theory approach.

PURPOSE: Prostate cancer (CaP) is the most common cancer in Black men (BM), and the number of Black CaP survivors is rapidly increasing. Although Black immigrants are among the fastest-growing and most heterogeneous ethnic groups in the USA, limited data exist regarding their CaP experiences. Therefore, this study aimed to explore and model the experiences of ethnically diverse Black men with CaP. METHODS: In-depth interviews were conducted with 34 participants: native-born BM (NBBM) (n = 17), African-born BM (ABBM) (n = 11), and Caribbean-born BM (CBBM) (n = 6) CaP survivors recruited through QR code-embedded flyers posted in Black businesses, clinics, social media platforms, and existing research networks within the USA. Guided by Charmaz's constructivist grounded theory methodology, the interviews were analyzed using constant comparison following key stages of initial, focused, and theoretical coding using Atlas.ti v23. RESULTS: Participants were thirty-four men aged 49-84 years (mean ± SD, 66 ± 8). Most were married (77%), likely to be diagnosed at stage I (35%), and treated with radiotherapy (56%). Our study findings explored the complex trajectory of Black prostate cancer (CaP) survivors, unveiling a comprehensive model termed "Journeying through Unfamiliar Terrain." Comprising three phases and 11 sub-phases, this model uniquely captures the pre-diagnosis awareness and post-treatment adaptation among survivors. CONCLUSION: The resulting theoretical model delineates the entire CaP survivorship process among BM, providing contextual and conceptual understanding for developing interventions and enhancing patient-centered care for ethnically diverse CaP survivors, pivotal in bridging the gaps in survivorship research and healthcare practices. IMPLICATIONS FOR CANCER SURVIVORS: Black CAP survivors experience significant burdens and challenges that impact their overall quality of life. Understanding the factors that impact the complex survivorship journey can inform design and implementation of interventions to address the multiple challenges and thus improve quality of life.

Systemic neutrophil degranulation and emergency granulopoiesis in patients with Clostridioides difficile infection.

OBJECTIVES: Clostridioides difficile infection (CDI) is characterized by neutrophilia in blood, with a high leukocyte count accompanying severe infection. In this study, we characterized peripheral blood neutrophil activation and maturity in CDI by (i) developing a method to phenotype stored neutrophils for disease-related developmental alterations and (ii) assessing neutrophil-associated biomarkers. METHODS: We stored fixed leukocytes from blood collected within 24 h of diagnosis from a cohort of hospitalized patients with acute CDI. Additional study cohorts included recurrent CDI patients at time of and two months after FMT therapy and a control healthy cohort. We assessed levels of neutrophil surface markers CD66b, CD11b, CD16 and CD10 by flow cytometry. Plasma neutrophil elastase and lipocalin-2 were measured using ELISA, while G-CSF, GM-CSF and cytokines were measured using O-link Proteomic technology. RESULTS: CD66b+ neutrophil abundance assessed by flow cytometry correlated well with complete blood counts, establishing that neutrophils in stored blood are sufficiently well-preserved for phenotyping by flow cytometry. Neutrophil abundance was significantly increased in CDI patients compared to healthy controls. Emergency granulopoiesis in acute CDI patients was evidenced by lower neutrophil surface expression of CD10, CD11b and CD16. CD10+ staining of neutrophils started to recover within 3-7 days of CDI treatment. Neutrophil activation and degranulation were higher in acute CDI as assessed by plasma neutrophil elastase and lipocalin-2. Biomarker levels in immunocompetent subjects were associated with recurrence and fatal outcomes. CONCLUSIONS: Neutrophil activation and emergency granulopoiesis characterize the early immune response in acute CDI, with plasma degranulation biomarkers predictive of disease severity.

The impact of existing total anti-toxin B IgG immunity in outcomes of recurrent Clostridioides difficile infection.

Late anti-toxin-B humoral immunity acquired after treatment is important for preventing recurrent Clostridioides difficile infection. We prospectively-measured anti-toxin-B IgG and neutralization titers at diagnosis as potential early predictors of recurrence. High anti-toxin-B-IgG/neutralizing antibodies were associated with short-lasting protection within 6-weeks, however, no difference in recurrence risk was observed by 90-days post-infection.

Quality of Life Assessment Among Ethnically Diverse Black Prostate Cancer Survivors: A Constructivist Grounded Theory Approach.

Purpose: Prostate cancer (CaP) is the most common cancer in Black men (BM), and the number of Black CaP survivors is rapidly increasing. Although Black immigrants are among the fastest-growing and most heterogeneous ethnic groups in the US, limited data exist regarding their CaP experiences. Therefore, this study aimed to explore and model the experiences of ethnically diverse Black men with CaP. Methods: In-depth interviews were conducted with 34 participants: Native-born BM (NBBM) (n=17), African-born BM (ABBM) (n=11), and Caribbean-born BM (CBBM) (n=6) CaP survivors recruited through QR-code embedded flyers posted in Black businesses, clinics, social media platforms, and existing research networks within the US. Guided by Charmaz's constructivist grounded theory methodology, the interviews were analyzed using constant comparison following key stages of initial, focused, and theoretical coding using Atlas.ti v23. Results: Participants were thirty-four men aged 49-84 years (mean±SD, 66±8). Most were married (77%), likely to be diagnosed at Stage I (35%), and treated with radiotherapy (56%). Our study findings explored the complex trajectory of Black prostate cancer (CaP) survivors, unveiling a comprehensive model termed "Journeying through Unfamiliar Terrain." Comprising three phases and 11 sub-phases, this model uniquely captures the pre-diagnosis awareness and post-treatment adaptation among survivors. Conclusion: The resulting theoretical model delineates the entire CaP survivorship process among BM, providing contextual and conceptual understanding for developing interventions and enhancing patient-centered care for ethnically diverse CaP survivors, pivotal in bridging the gaps in survivorship research and healthcare practices.

Publics' knowledge of, attitude to and motivation towards health-related genomics: a scoping review.

The use of genomic data in research and genomic information in clinical care is increasing as technologies advance and sequencing costs decrease. Using Rogers' Diffusion of Innovation (DOI) theory as a framework we reviewed recent literature examining publics' current knowledge of, attitude to, and motivation towards health-related genomics in clinical and research settings. The population of interest was described as 'publics' to denote the heterogeneity of 'the public'. Eligible studies were published in English between 2016-2022. We retrieved 1657 records, with 278 full-text reviewed against the eligibility criteria and concept definitions. In total, 99 articles were included in the review and descriptive numerical summaries were collated. Knowledge literature was categorized using deductive thematic analysis. For attitude and motivation, literature was coded using an analytic framework developed by the authors. There was wide variability in concept definition and measurement across studies. Overall, there was general positivity about genomics, with high awareness but little familiarity or factual knowledge. Publics had high expectations of genomics and perceived that it could provide them with information for their future. Only a few key attitudes were found to be important as motivators or barriers for participation in genomics; these were related to personal and clinical utility of the information. Context was often missing from studies, decreasing the utility of findings for implementation or public engagement. Future research would benefit by using theory-driven approaches to assess relevant publics' knowledge and attitudes of specific contexts or applications to support genomic implementation and informed decision-making.

Pulmonary Function and Survival 1 Year After Dupilumab Treatment of Acute Moderate to Severe Coronavirus Disease 2019: A Follow-up Study From a Phase 2a Trial.

Background: We previously conducted a phase 2a randomized placebo-controlled trial of 40 subjects to assess the efficacy and safety of dupilumab use in people hospitalized with coronavirus disease 2019 (COVID-19) (NCT04920916). Based on our preclinical data suggesting that downstream pulmonary dysfunction with COVID-19 induced type 2 inflammation, we contacted patients from our phase 2a study at 1 year for assessment of post-COVID-19 conditions. Methods: Subjects at 1 year after treatment underwent pulmonary function tests, high-resolution computed tomographic imaging, symptom questionnaires, neurocognitive assessments, and serum immune biomarker analysis, with subject survival also monitored. The primary outcome was the proportion of abnormal diffusion capacity for carbon monoxide (DLCO) or 6-minute walk test (6MWT) at the 1-year visit. Results: Of those survivors who consented to 1-year visits (n = 16), subjects who had originally received dupilumab were less likely than those who received placebo to have an abnormal DLCO or 6MWT (Fisher exact P = .011; adjusted P = .058). As a secondary endpoint, we saw that 16% of subjects in the dupilumab group died by 1 year compared to 38% in the placebo group, though this was not statistically significant (log-rank P = .12). We did not find significant differences in neurocognitive testing, symptoms, or chest computed tomography between treatment groups but observed a larger reduction in eotaxin levels in those who received dupilumab. Conclusions: In this observational study, subjects who received dupilumab during acute COVID-19 hospitalization were less likely to have a reduced DLCO or 6MWT, with a nonsignificant trend toward reduced mortality at 1 year compared to placebo.

Systematic review of the uptake and outcomes from returning secondary findings to adult participants in research genomic testing.

The increasing use of genomic sequencing in research means secondary findings (SF) is more frequently detected and becoming a more pressing issue for researchers. This is reflected by the recent publication of multiple guidelines on this issue, calling for researchers to have a plan for managing SF prior to commencing their research. A deeper understanding of participants' experiences and outcomes from receiving SF is needed to ensure that the return of SF is conducted ethically and with adequate support. This review focuses on the uptake and outcomes of receiving actionable SF for research participants. This review included studies from January 2010 to January 2023. Databases searched included Medline, Embase, PsycINFO, and Scopus. Of the 3903 studies identified, 29 were included in the analysis. The uptake of SF ranged between 20% and 97%, and outcomes were categorized into psychological, clinical, lifestyle and behavioral, and family outcomes. The results indicate there is minimal psychological impact from receiving SF. Almost all participants greatly valued receiving SF. These findings highlight considerations for researchers when returning results, including the importance of involving genetic health professionals in consenting, results return process, and ensuring continuity of care by engaging healthcare providers.

Pulmonary function and survival one year after dupilumab treatment of acute moderate to severe COVID-19: A follow up study from a Phase IIa trial.

Background: We previously conducted a Phase IIa randomized placebo-controlled trial of 40 subjects to assess the efficacy and safety of dupilumab use in those hospitalized with COVID-19 (NCT04920916). Based on our pre-clinical data suggesting downstream pulmonary dysfunction with COVID-19 induced type 2 inflammation, we contacted patients from our Phase IIa study at 1 year for assessment of Post Covid-19 Conditions (PCC). Methods: Subjects at 1 year after treatment underwent pulmonary function testing (PFTs), high resolution computed tomography (HRCT) imaging, symptom questionnaires, neurocognitive assessments, and serum immune biomarker analysis, with subject survival also monitored. The primary outcome was the proportion of abnormal PFTs, defined as an abnormal diffusion capacity for carbon monoxide (DLCO) or 6-minute walk testing (6MWT) at the 1-year visit. Results: Sixteen of the 29 one-year survivors consented to the follow up visit. We found that subjects who had originally received dupilumab were less likely to have abnormal PFTs compared to those who received placebo (Fisher's exact p=0.011, adjusted p=0.058). We additionally found that 3 out of 19 subjects (16%) in the dupilumab group died by 1 year compared to 8 out of 21 subjects (38%) in the placebo group (log rank p=0.12). We did not find significant differences in neurocognitive testing, symptoms or CT chest imaging between treatment groups but observed evidence of reduced type 2 inflammation in those who received dupilumab. Conclusions: We observed evidence of reduced long-term morbidity and mortality from COVID-19 with dupilumab treatment during acute hospitalization when added to standard of care regimens.

TRAFfic signals: High-throughput CAR discovery in NK cells reveals novel TRAF-binding endodomains that drive enhanced persistence and cytotoxicity.

Natural killer (NK) cells are a promising alternative therapeutic platform to CAR T cells given their favorable safety profile and potent killing ability. However, CAR NK cells suffer from limited persistence in vivo , which is, in part, thought to be the consequence of limited cytokine signaling. To address this challenge, we developed an innovative high-throughput screening strategy to identify CAR endodomains that could drive enhanced persistence while maintaining potent cytotoxicity. We uncovered a family of TRAF-binding endodomains that outperform benchmarks in primary NK cells along dimensions of persistence and cytotoxicity, even in low IL-2 conditions. This work highlights the importance of cell-type-specific cell therapy engineering and unlocks a wide range of high-throughput molecular engineering avenues in NK cells.

Patterns and drivers of macroalgal 'blue carbon' transport and deposition in near-shore coastal environments.

The role of macroalgae (seaweed) as a global contributor to carbon drawdown within marine sediments - termed 'blue carbon' - remains uncertain and controversial. While studies are needed to validate the potential for macroalgal­carbon sequestration in marine and coastal sediments, fundamental questions regarding the fate of dislodged macroalgal biomass need to be addressed. Evidence suggests macroalgal biomass may be advected and deposited within other vegetated coastal ecosystems and down to the deep ocean; however, contributions to near-shore sediments within coastal waters remain uncertain. In this study a combination of eDNA metabarcoding and surficial sediment sampling informed by seabed mapping from different physical environments was used to test for the presence of macroalgal carbon in near-shore coastal sediments in south-eastern Australia, and the physical factors influencing patterns of macroalgal transport and deposition. DNA products for a total of 68 macroalgal taxa, representing all major macroalgal groups (Phaeophyceae, Rhodophyta, and Chlorophyta) were successfully detected at 112 near-shore locations. These findings confirm the potential for macroalgal biomass to be exported into near-shore sediments and suggest macroalgal carbon donors could be both speciose and diverse. Modelling suggested that macroalgal transport and deposition, and total organic carbon (TOC), are influenced by complex interactions between several physical environmental factors including water depth, sediment grain size, wave orbital velocity, current speed, current direction, and the extent of the infralittoral zone around depositional areas. Extrapolation of the optimised model was used to predict spatial patterns of macroalgal deposition and TOC across the coastline and to identify potentially important carbon sinks. This study builds on recent studies providing empirical evidence for macroalgal biomass deposits in near-shore sediments, and a framework for predicting the spatial distribution of potential carbon sinks and informing future surveys aimed at determining the potential for long-term macroalgal carbon sequestration in marine sediments.

Development and evaluation of a novel educational program for providers on the use of polygenic risk scores.

PURPOSE: This study aimed to develop an online educational program for using polygenic risk score (PRS) for breast and ovarian cancer risk assessments and to evaluate the impact on the attitudes, confidence, knowledge, and preparedness of genetic health care providers (GHPs). METHODS: The educational program comprises an online module that covers the theoretical aspects of PRS and a facilitated virtual workshop with prerecorded role-plays and case discussions. Data were collected in pre- and posteducation surveys. Eligible participants were GHPs working in Australian familial cancer clinics registered to recruit patients for a breast and ovarian cancer PRS clinical trial (n = 12). RESULTS: A total of 124 GHPs completed the PRS education, of whom 80 (64%) and 67 (41%) completed the pre- and posteducation surveys, respectively. Before education, GHPs reported limited experience, confidence, and preparedness using PRS, but they recognized its potential benefits. After education, GHPs indicated improved attitudes (P ≤ .001), confidence (P ≤ .001), knowledge (P ≤ .001), and preparedness (P ≤ .001) to use PRS. Most GHPs thought that the program entirely met their learning needs (73%) and was completely relevant to their clinical practice (88%). GHPs identified PRS implementation barriers, including limited funding models, diversity issues, and need for clinical guidelines. CONCLUSION: Our education program improved GHP attitudes, confidence, knowledge, and preparedness for using PRS/personalized risk and provides a framework for the development of future programs.

Quantifying blue carbon stocks and the role of protected areas to conserve coastal wetlands.

Vegetated coastal ecosystems, in particular mangroves, tidal marshes and seagrasses are highly efficient at sequestering and storing carbon, making them valuable assets for climate change mitigation and adaptation. The state of Queensland, in northeastern Australia, contains almost half of the total area of these blue carbon ecosystems in the country, yet there are few detailed regional or state-wide assessments of their total sedimentary organic carbon (SOC) stocks. We compiled existing SOC data and used boosted regression tree models to evaluate the influence of environmental variables in explaining the variability in SOC stocks, and to produce spatially explicit blue carbon estimates. The final models explained 75 % (for mangroves and tidal marshes) and 65 % (for seagrasses) of the variability in SOC stocks. Total SOC stocks in the state of Queensland were estimated at 569 ± 98 Tg C (173 ± 32 Tg C, 232 ± 50 Tg C, and 164 ± 16 Tg C from mangroves, tidal marshes and seagrasses, respectively). Regional predictions for each of Queensland's eleven Natural Resource Management regions revealed that 60 % of the state's SOC stocks occurred within three regions (Cape York, Torres Strait and Southern Gulf Natural Resource Management regions) due to a combination of high values of SOC stocks and large areas of coastal wetlands. Protected areas in Queensland play an important role in conserving SOC assets in Queensland's coastal wetlands. For example, ~19 Tg C within terrestrial protected areas, ~27 Tg C within marine protected areas and ~ 40 Tg C within areas of matters of State Environmental Significance. Using multi-decadal (1987-2020) mapped distributions of mangroves in Queensland; we found that mangrove area increased by approximately 30,000 ha from 1987 to 2020, which led to temporal fluctuations in mangrove plant and SOC stocks. We estimated that plant stocks decreased from ~45 Tg C in 1987 to ~34.2 Tg C in 2020, while SOC stocks remained relatively constant from ~107.9 Tg C in 1987 to 108.0 Tg C in 2020. Considering the level of current protection, emissions from mangrove deforestation are potentially very low; therefore, representing minor opportunities for mangrove blue carbon projects in the region. Our study provides much needed information on current trends in carbon stocks and their conservation in Queensland's coastal wetlands, while also contributing to guide future management actions, including blue carbon restoration projects.

Novel Biomarkers, Including tcdB PCR Cycle Threshold, for Predicting Recurrent Clostridioides difficile Infection.

Traditional clinical models for predicting recurrent Clostridioides difficile infection do not perform well, likely owing to the complex host-pathogen interactions involved. Accurate risk stratification using novel biomarkers could help prevent recurrence by improving underutilization of effective therapies (i.e., fecal transplant, fidaxomicin, bezlotoxumab). We used a biorepository of 257 hospitalized patients with 24 features collected at diagnosis, including 17 plasma cytokines, total/neutralizing anti-toxin B IgG, stool toxins, and PCR cycle threshold (CT) (a proxy for stool organism burden). The best set of predictors for recurrent infection was selected by Bayesian model averaging for inclusion in a final Bayesian logistic regression model. We then used a large PCR-only data set to confirm the finding that PCR CT predicts recurrence-free survival using Cox proportional hazards regression. The top model-averaged features were (probabilities of >0.05, greatest to least): interleukin 6 (IL-6), PCR CT, endothelial growth factor, IL-8, eotaxin, IL-10, hepatocyte growth factor, and IL-4. The accuracy of the final model was 0.88. Among 1,660 cases with PCR-only data, cycle threshold was significantly associated with recurrence-free survival (hazard ratio, 0.95; P < 0.005). Certain biomarkers associated with C. difficile infection severity were especially important for predicting recurrence; PCR CT and markers of type 2 immunity (endothelial growth factor [EGF], eotaxin) emerged as positive predictors of recurrence, while type 17 immune markers (IL-6, IL-8) were negative predictors. In addition to novel serum biomarkers (particularly, IL-6, EGF, and IL-8), the readily available PCR CT may be critical to augment underperforming clinical models for C. difficile recurrence.

Human Genetics Society of Australasia Position Statement: Use of Polygenic Scores in Clinical Practice and Population Health.

Considerable progress continues to be made with regards to the value and use of disease associated polygenic scores (PGS). PGS aim to capture a person's genetic liability to a condition, disease, or a trait, combining information across many risk variants and incorporating their effect sizes. They are already available for clinicians and consumers to order in Australasia. However, debate is ongoing over the readiness of this information for integration into clinical practice and population health. This position statement provides the viewpoint of the Human Genetics Society of Australasia (HGSA) regarding the clinical application of disease-associated PGS in both individual patients and population health. The statement details how PGS are calculated, highlights their breadth of possible application, and examines their current challenges and limitations. We consider fundamental lessons from Mendelian genetics and their continuing relevance to PGS, while also acknowledging the distinct elements of PGS. Use of PGS in practice should be evidence based, and the evidence for the associated benefit, while rapidly emerging, remains limited. Given that clinicians and consumers can already order PGS, their current limitations and key issues warrant consideration. PGS can be developed for most complex conditions and traits and can be used across multiple clinical settings and for population health. The HGSA's view is that further evaluation, including regulatory, implementation and health system evaluation are required before PGS can be routinely implemented in the Australasian healthcare system.

Inhibiting myostatin signaling partially mitigates structural and functional adaptations to hindlimb suspension in mice.

Novel treatments for muscle wasting are of significant value to patients with disease states that result in muscle weakness, injury recovery after immobilization and bed rest, and for astronauts participating in long-duration spaceflight. We utilized an anti-myostatin peptibody to evaluate how myostatin signaling contributes to muscle loss in hindlimb suspension. Male C57BL/6 mice were left non-suspended (NS) or were hindlimb suspended (HS) for 14 days and treated with a placebo vehicle (P) or anti-myostatin peptibody (D). Hindlimb suspension (HS-P) resulted in rapid and significantly decreased body mass (-5.6% by day 13) with hindlimb skeletal muscle mass losses between -11.2% and -22.5% and treatment with myostatin inhibitor (HS-D) partially attenuated these losses. Myostatin inhibition increased hindlimb strength with no effect on soleus tetanic strength. Soleus mass and fiber CSA were reduced with suspension and did not increase with myostatin inhibition. In contrast, the gastrocnemius showed histological evidence of wasting with suspension that was partially mitigated with myostatin inhibition. While expression of genes related to protein degradation (Atrogin-1 and Murf-1) in the tibialis anterior increased with suspension, these atrogenes were not significantly reduced by myostatin inhibition despite a modest activation of the Akt/mTOR pathway. Taken together, these findings suggest that myostatin is important in hindlimb suspension but also motivates the study of other factors that contribute to disuse muscle wasting. Myostatin inhibition benefitted skeletal muscle size and function, which suggests therapeutic potential for both spaceflight and terrestrial applications.

Models of communication for polygenic scores and associated psychosocial and behavioral effects on recipients: A systematic review.

PURPOSE: This study aimed to systematically review current models for communicating polygenic scores (PGS) and psycho-behavioral outcomes of receiving PGSs. METHODS: Original research on communicating PGSs and reporting on psycho-behavioral outcomes was included. Search terms were applied to 5 databases and were limited by date (2009-2021). RESULTS: In total, 28 articles, representing 17 studies in several disease settings were identified. There was limited consistency in PGS communication and evaluation/reporting of outcomes. Most studies (n = 14) presented risk in multiple ways (ie, numerically, verbally, and/or visually). Three studies provided personalized lifestyle advice and additional resources. Only 1 of 17 studies reported using behavior change theory to inform their PGS intervention. A total of 8 studies found no evidence of long-term negative psychosocial effects up to 12 months post result. Of 14 studies reporting on behavior, 9 found at least 1 favorable change after PGS receipt. When stratified by risk, 7 out of 9 studies found high PGS was associated with favorable changes including lifestyle, medication, and screening. Low-risk PGS was not associated with maladaptive behaviors (n = 4). CONCLUSION: PGS has the potential to benefit health behavior. High variability among studies emphasizes the need for developing standardized guidelines for communicating PGSs and evaluating psycho-behavioral outcomes. Our findings call for development of best communication practices and evidence-based interventions informed by behavior change theories.

Attitudes of Australian dermatologists on the use of genetic testing: A cross-sectional survey with a focus on melanoma.

Background: Melanoma genetic testing reportedly increases preventative behaviour without causing psychological harm. Genetic testing for familial melanoma risk is now available, yet little is known about dermatologists' perceptions regarding the utility of testing and genetic testing ordering behaviours. Objectives: To survey Australasian Dermatologists on the perceived utility of genetic testing, current use in practice, as well as their confidence and preferences for the delivery of genomics education. Methods: A 37-item survey, based on previously validated instruments, was sent to accredited members of the Australasian College of Dermatologists in March 2021. Quantitative items were analysed statistically, with one open-ended question analysed qualitatively. Results: The response rate was 56% (256/461), with 60% (153/253) of respondents between 11 and 30 years post-graduation. While 44% (112/252) of respondents agreed, or strongly agreed, that genetic testing was relevant to their practice today, relevance to future practice was reported significantly higher at 84% (212/251) (t = -9.82, p < 0.001). Ninety three percent (235/254) of respondents reported rarely or never ordering genetic testing. Dermatologists who viewed genetic testing as relevant to current practice were more likely to have discussed (p < 0.001) and/or offered testing (p < 0.001). Respondents indicated high confidence in discussing family history of melanoma, but lower confidence in ordering genetic tests and interpreting results. Eighty four percent (207/247) believed that genetic testing could negatively impact life insurance, while only 26% (63/244) were aware of the moratorium on using genetic test results in underwriting in Australia. A minority (22%, 55/254) reported prior continuing education in genetics. Face-to-face courses were the preferred learning modality for upskilling. Conclusion: Australian Dermatologists widely recognise the relevance of genetic testing to future practice, yet few currently order genetic tests. Future educational interventions could focus on how to order appropriate genetic tests and interpret results, as well as potential implications on insurance.

Repressed Ang 1-7 in COVID-19 Is Inversely Associated with Inflammation and Coagulation.

The coronavirus SARS-CoV-2 infects host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, which belongs to an anti-inflammatory, anti-thrombotic counter-regulatory arm of the renin-angiotensin system (RAS). ACE2 dysfunction and RAS dysregulation has been explored as a driving force in acute respiratory distress syndrome (ARDS), but data from COVID-19 patients has been inconsistent and inconclusive. We sought to identify disruptions of the classical (ACE)/angiotensin (Ang) II/Ang II type-1 receptor (AT1R) and the counter-regulatory ACE2/Ang 1-7/Mas Receptor (MasR) pathways in patients with COVID-19 and correlate these with severity of infection and markers of inflammation and coagulation. Ang II and Ang 1-7 levels in plasma were measured by enzyme-linked immunosorbent assay (ELISA) for 230 patients, 166 of whom were SARS-CoV-2+. Ang 1-7 was repressed in COVID-19 patients compared to that in SARS-CoV-2 negative outpatient controls. Since the control cohort was less sick than the SARS-CoV-2+ group, this association between decreased Ang 1-7 and COVID-19 cannot be attributed to COVID-19 specifically as opposed to critical illness more generally. Multivariable logistic regression analyses demonstrated that every 10-pg/mL increase in plasma Ang 1-7 was associated with a 3% reduction in the odds of hospitalization (adjusted odds ratio [AOR] 0.97, confidence interval [CI] 0.95 to 0.99) and a 3% reduction in odds of requiring oxygen supplementation (AOR 0.97, CI 0.95 to 0.99) and/or ventilation (AOR 0.97, CI 0.94 to 0.99). Ang 1-7 was also inversely associated with pro-inflammatory cytokines and d-dimer in this patient cohort, suggesting that reduced activity in this protective counter-regulatory arm of the RAS contributes to the hyper-immune response and diffuse coagulation activation documented in COVID-19. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a unique disease, COVID-19, which ranges in severity from asymptomatic to causing severe respiratory failure and death. Viral transmission throughout the world continues at a high rate despite the development and widespread use of effective vaccines. For those patients who contract COVID-19 and become severely ill, few therapeutic options have been shown to provide benefits and mortality rates are high. Additionally, the pathophysiology underlying COVID-19 disease presentation, progression, and severity is incompletely understood. The significance of our research is in confirming the role of renin-angiotensin system dysfunction in COVID-19 pathogenesis in a large cohort of patients with diverse disease severity and outcomes. Additionally, to our knowledge, this is the first study to pair angiotensin peptide levels with inflammatory and thrombotic markers. These data support the role of ongoing clinical trials examining renin-angiotensin system-targeted therapeutics for the treatment of COVID-19.