Characterization of the genomes of cluster CT Gordonia terrae phages, Horseradish and Yummy.

The genomes of lytic, cluster CT Gordonia terrae phages, Horseradish and Yummy, are 45,764 and 45,878 bp in length, respectively, and each encodes 71 protein-coding genes. The genomes are identical in sequence with the exception of a 38-bp insertion/deletion in the minor tail protein, gp26.

An implication of the mitochondrial carrier SLC25A3 as an oxidative stress modulator in NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is a type of steatosis not associated with excessive alcohol intake and includes nonalcoholic steatohepatitis (NASH), which can progress to advanced fibrosis and hepatocellular carcinoma. Mitochondrial dysfunction causes oxidative stress, triggering hepatocyte death and inflammation; therefore, the present study aimed to explore relationship between mitochondrial carriers and oxidative stress. Firstly, we established a high fat diet (HFD)-fed ICR mouse NAFLD model characterized by obesity with insulin resistance and found transcriptional upregulation of Slc25a17 and downregulation of Slc25a3 (isoform B) and Slc25a13 in their fatty liver. A mitochondrial phosphate and Cu carrier, SLC25A3, was further studied in wild-type (wt) and SLC25A3-defective HepG2 cells (C1 and C3). SLC25A3 deficiency had insignificant effect on mitochondrial membrane potential (MtMP) and oxygen consumption rate (OCR) in untreated cells but suppressed them when cells were exposed to oleic acid. C1 and C3 cells were prone to produce reactive oxygen species (ROS), and increased ROS was associated with reduced mRNA expression of glutathione peroxidase (GPX) 1 and glutathione disulfide reductase (GSX) in these cell lines. Interestingly, cytoplasmic and mitochondrial Cu accumulation significantly reduced in C1 cells, demonstrating a predominant contribution of SLC25A3 to Cu transport into mitochondrial matrix. Cytotoxicity of free fatty acids was unchanged between wt and SLC25A3-deficient cells. These results indicate that reduced expression of SLC25A3 in fatty liver contributes to electron leak from mitochondria by limiting Cu availability, rendering hepatocytes more susceptible to oxidative stress. This study provides evidence that SLC25A3 is a novel risk factor for developing NASH.

Heterogeneity of the group B streptococcal type VII secretion system and influence on colonization of the female genital tract.

Type VIIb secretion systems (T7SSb) in Gram-positive bacteria facilitate physiology, interbacterial competition, and/or virulence via EssC ATPase-driven secretion of small ɑ-helical proteins and toxins. Recently, we characterized T7SSb in group B Streptococcus (GBS), a leading cause of infection in newborns and immunocompromised adults. GBS T7SS comprises four subtypes based on variation in the C-terminus of EssC and the repertoire of downstream effectors; however, the intraspecies diversity of GBS T7SS and impact on GBS-host interactions remains unknown. Bioinformatic analysis indicates that GBS T7SS loci encode subtype-specific putative effectors, which have low interspecies and inter-subtype homology but contain similar domains/motifs and therefore may serve similar functions. We further identify orphaned GBS WXG100 proteins. Functionally, we show that GBS T7SS subtype I and III strains secrete EsxA in vitro and that in subtype I strain CJB111, esxA1 appears to be differentially transcribed from the T7SS operon. Furthermore, we observe subtype-specific effects of GBS T7SS on host colonization, as CJB111 subtype I but not CNCTC 10/84 subtype III T7SS promotes GBS vaginal colonization. Finally, we observe that T7SS subtypes I and II are the predominant subtypes in clinical GBS isolates. This study highlights the potential impact of T7SS heterogeneity on host-GBS interactions.

Exploring knowledge, perspectives, and misperceptions of palliative care: A mixed methods analysis.

OBJECTIVES: To better understand palliative care knowledge and beliefs of patients with stage II or greater bladder cancer and their caregivers. SUBJECTS AND METHODS: Participants were primarily patients diagnosed with muscle-invasive or locally advanced bladder cancer. All were encouraged to enroll with a caregiver (defined as the individual who most closely assists with a patient's care). Participants completed a survey and semistructured interview. Applied thematic analysis techniques were used to analyze the interview data. In total, we recruited 16 dyads, 11 patients who participated alone, and 1 caregiver who participated alone. RESULTS: Patients and caregivers had high levels of palliative care knowledge and there was no difference in baseline knowledge. Palliative care receptivity was also high, with most participants stating that they would be "very likely" to consider palliative care for themselves or a loved one. However, based on the analysis of multiple-choice palliative care questions and interview transcripts, many participants lacked a nuanced understanding of palliative care and harbored many common misconceptions of the basic tenants. Five main themes emerged related to palliative care: (1) Participants have a general lack of awareness of it, (2) Participants associate it with hospice and death, (3) Participants view it as primarily emotional or psychological support, (4) Participants believe it is for patients without a strong support system, and (5) Participants believe it is for people who have "given up." CONCLUSIONS: High educational attainment and baseline palliative care knowledge did not preclude the most common misperceptions related to palliative care. These study results indicate that patients need clearer counseling regarding the definition, goals, benefits, and availability of palliative care.

Heterogeneity of the group B streptococcal type VII secretion system and influence on colonization of the female genital tract.

Type VIIb secretion systems (T7SSb) in Gram-positive bacteria facilitate physiology, interbacterial competition, and/or virulence via EssC ATPase-driven secretion of small ɑ-helical proteins and toxins. Recently, we characterized T7SSb in group B Streptococcus (GBS), a leading cause of infection in newborns and immunocompromised adults. GBS T7SS comprises four subtypes based on variation in the C-terminus of EssC and the repertoire of downstream effectors; however, the intra-species diversity of GBS T7SS and impact on GBS-host interactions remains unknown. Bioinformatic analysis indicates that GBS T7SS loci encode subtype-specific putative effectors, which have low inter-species and inter-subtype homology but contain similar domains/motifs and therefore may serve similar functions. We further identify orphaned GBS WXG100 proteins. Functionally, we show that GBS T7SS subtype I and III strains secrete EsxA in vitro and that in subtype I strain CJB111, esxA1 appears to be differentially transcribed from the T7SS operon. Further, we observe subtype-specific effects of GBS T7SS on host colonization, as subtype I but not subtype III T7SS promotes GBS vaginal persistence. Finally, we observe that T7SS subtypes I and II are the predominant subtypes in clinical GBS isolates. This study highlights the potential impact of T7SS heterogeneity on host-GBS interactions.

Developing a Patient-Reported Outcome Measure for Radionuclide Therapy for Prostate Cancer.

The field of radionuclide therapy (RNT) for prostate cancer (PC) is growing rapidly, with recent Food and Drug Administration approval of the first 177Lu-PSMA ligand. We aimed to develop the first patient-reported outcome (PRO) measure for PC patients receiving RNT. Methods: We identified relevant symptoms and toxicities by reviewing published trials and interviews with PC patients receiving RNT (n = 29), caregivers (n = 14), and clinicians (n = 11). Second, we selected items for measure inclusion. Third, we refined the item list with input from experts in RNTs and PROs. Fourth, we finalized the Functional Assessment of Cancer Therapy-Radionuclide Therapy (FACT-RNT) with patient input. Results: This multistep process yielded a brief 15-item measure deemed by key stakeholders to be relevant and useful in the context of RNT for PC. Conclusion: The FACT-RNT is a new standardized tool to monitor relevant symptoms and toxicities among PC patients in RNT trials and real-world settings.

Psychological Impact of COVID-19 on Oncology Patients: Perceptions of Oncology Health Care Providers.

The COVID-19 pandemic profoundly impacted psychological well-being worldwide. Oncology health care professionals' (OHCPs') perceptions of psychological effects of COVID-19 among people in active cancer treatment were explored. Semi-structured interviews with a purposive sample of OHCPs actively providing care were conducted. Interviews were audio-recorded, transcribed, and coded using Atlas.ti v8 and thematic analysis. In total, 30 OHCPs participated. Most were registered nurses (70%), worked in outpatient setting (56.7%) and were in their current position 1-5 years (53.3%). Overarching themes are as follows: (a) cancer treatment disrupted due to patients' fear of exposure to COVID-19; (b) social distancing restrictions caused discontinued social support and supportive services that exacerbated psychological distress; (c) pandemic-related stressors led to overwhelmed coping skills; and (d) OHCPs played a vital role in providing emotional support and connecting patients with family/friends through technology. Behavioral health interventions should focus within the "new world of COVID-19" of reduced face-to-face support and increased online support for patients.

Genomic Characterization of the Cluster CZ4 Gordonia terrae Phage Oregano.

Oregano is a novel cluster CZ4 bacteriophage isolated from the soil using the bacterial host Gordonia terrae. The Oregano genome is 47,575 bp long and encodes two tyrosine integrases and a toxin/antitoxin system. It shares an immunity repressor with both Gordonia and Mycobacterium phages that spans 7 clusters.

Genome Sequence of the Cluster CD Gordonia Phage Widow.

Widow is a novel cluster CD bacteriophage isolated from a soil sample using the bacterial host Gordonia terrae. The Widow genome is 43,656 bp in length and encodes 64 protein-coding genes and no tRNAs. The genome shares 52 to 92% gene content with other cluster CD members.

Genome Sequence of Singleton Gordonia terrae Bacteriophage Finkle.

Bacteriophage Finkle is a temperate siphovirus isolated from soil on Gordonia terrae. The 47,895-bp genome has a GC content of 66.6% and encodes 84 protein-coding genes. The genome is not closely related to sequences in the Actinobacteriophage database, sharing less than 35% gene content, and was classified as a singleton.

"I Beat Cancer to Feel Sick:" Qualitative Experiences of Sleep Disturbance in Black Breast Cancer Survivors and Recommendations for Culturally Targeted Sleep Interventions.

BACKGROUND: Sleep disturbance is common and distressing among cancer survivors. Black breast cancer survivors (BBCS) suffer disproportionately from sleep disturbance, yet there is limited research on how to address this issue. PURPOSE: This study aimed to understand the multifaceted experiences of sleep disturbance among BBCS and how to culturally target a mobile health (mHealth) intervention to improve sleep outcomes in BBCS. METHODS: Semi-structured interviews were conducted in a purposive sample of 10 BBCS. Interviews were audio-recorded, transcribed, and coded for key barriers to sleep and potential solutions to incorporate into behavioral interventions using NVivo 12. Inductive applied thematic analysis techniques were employed to identify emergent themes. RESULTS: Ten BBCS (mean age = 54, SD = 10) described their experiences of sleep disturbance with themes including: (1) barriers to quality sleep (e.g., cancer worry, personal responsibilities), (2) psychosocial impacts of sleep disturbance (e.g., fatigue, distress), and (3) commonly used strategies to improve sleep. The second section discusses suggestions for developing mHealth interventions to improve sleep for BBCS including: (1) feedback on an existing mHealth intervention and (2) intervention topics suggested by BBCS. CONCLUSIONS: Our findings highlight the challenges associated with sleep disturbance in BBCS. Participants report culturally targeted mHealth interventions are needed for BBCS who experience chronic sleep disturbance that affects their overall quality of life. These interventions should address coping with sleep-related issues relevant to many breast cancer survivors and BBCS (e.g., sexual intimacy, fear of cancer recurrence) and should incorporate intervention strategies acceptable to BBCS (e.g., prayer, meditation).

Cancer Screening Among Rural and Urban Clinics During COVID-19: A Multistate Qualitative Study.

PURPOSE: The effects of COVID-19 have been understudied in rural areas. This study sought to (1) identify cancer screening barriers and facilitators during the pandemic in rural and urban primary care practices, (2) describe implementation strategies to support cancer screening, and (3) provide recommendations. METHODS: A qualitative study was conducted (N = 42) with primary care staff across 20 sites. Individual interviews were conducted through videoconference from August 2020 to April 2021 and recorded, transcribed, and analyzed using deductive and inductive coding (hybrid approach) in NVivo 12 Plus. Practices included federally qualified health centers, tribal health centers, rural health clinics, hospital/health system-owned clinics, and academic medical centers across 10 states including urban (55%) and rural (45%) sites. Staff included individuals serving in the dual role of health care provider and administrator (21.4%), health care administrator (23.8%), physician (19.0%), advanced practice provider (11.9%), or resident (23.8%). The interviews assessed perceptions about cancer screening barriers and facilitators, implementation strategies, and future recommendations. RESULTS: Participants reported multilevel barriers to cancer screening including policy-level (eg, elective procedure delays), organizational (eg, backlogs), and individual (eg, patient cancellation). Several facilitators to screening were noted, such as home-based testing, using telehealth, and strong partnerships with referral sites. Practices used strategies to encourage screening, such as incentivizing patients and providers and expanding outreach. Rural clinics reported challenges with backlogs, staffing, telehealth implementation, and patient outreach. CONCLUSION: Primary care staff used innovative strategies during the pandemic to promote cancer screening. Unresolved challenges (eg, backlogs and inability to implement telehealth) disproportionately affected rural clinics.

'They say you can get addicted': Exploring factors that fuel the fear of addiction to prescription opioids among cancer survivors.

OBJECTIVES: To explore misconceptions regarding addiction potential of prescription opioids among cancer survivors. METHODS: A qualitative study using semi-structured interviews were conducted with a purposive sample of cancer survivors (N = 25) treated with prescription opioids for pain management. Interviews were audio recorded, transcribed and coded using Atlas.ti version 8. Inductive applied thematic analysis techniques were employed to identify emergent themes. RESULTS: The majority of participants were breast cancer survivors (88%) who underwent a combination of surgery, chemotherapy and radiation (72%). Thematic analysis revealed that (1) cancer survivors view opioids as an illicit drug, (2) media narrative of the opioid epidemic increased negative perception of opioid use for cancer-related pain, (3) perceptions of opioids were also informed by experiences of friends and family with an opioid use disorder, (4) poor understanding of terminology resulted in misconceptions of opioid use and addiction and (5) fear of opioid addiction resulted in unrelieved cancer pain and poor quality of life. CONCLUSION: Our findings support previously identified concerns among cancer patients about fear of addiction to opioids, a barrier to effective pain management. It highlights the importance for health care providers caring for cancer survivors to continue to address misconceptions about prescribed opioids.

The LCP Family Protein, Psr, Is Required for Cell Wall Integrity and Virulence in Streptococcus agalactiae.

A robust cell envelope is the first line of protection for an infecting pathogen when encountering the immune defense of its host. In Gram-positive organisms, LytR-CpsA-Psr (LCP) family proteins play a major role in the synthesis and assembly of the cell envelope. While these proteins could be considered for potential new drug targets, not enough is known about how they function to support the integrity of the cell wall. Streptococcus agalactiae (group B streptococcus or GBS) is known to encode at least three LCP family proteins, including CpsA, LytR (BrpA) and Psr. Using strains of GBS that have mutations in two of the three LCP proteins, we were able to determine a role for these proteins in GBS cell wall integrity. The results presented here demonstrate that the absence of Psr results in a decreased growth rate, decreased viability over time, inconsistent cocci morphology and diminished cell wall integrity, as well as an increased penicillin susceptibility, decreased capsule levels and attenuation in virulence in a zebrafish model of infectious disease. A strain that is missing two of the LCP family proteins, CpsA and Psr, exhibits an increase in these defective phenotypes, indicating that CpsA and Psr are partially redundant in function.

Framing Cancer Survivors' Access to and Use and Disposal of Prescribed Opioids Within the Opioid Epidemic.

PURPOSE: To explore cancer survivors' access to and use and disposal of opioids in the context of the opioid epidemic. PARTICIPANTS & SETTING: Community-based recruitment strategies were employed for individuals aged 18 years or older who were previously diagnosed with cancer, completed cancer treatment within the past five years, or were cancer free, and who were prescribed opioids for cancer-related pain. METHODOLOGIC APPROACH: This qualitative study used semistructured interviews. Data were analyzed using applied thematic analysis techniques. FINDINGS: Themes included the following: (a) restrictive policies affecting opioid access and supply, (b) decreased opioid use because of concerns of addiction and other opioid-related side effects, and (c) lack of clarity on safeguarding and disposal of opioids. IMPLICATIONS FOR NURSING: Cancer survivors may encounter barriers to opioid access, alter medication-taking behavior over fear of addiction and side effects, and face inadequate education regarding proper disposal of opioids. Nurses can advocate for appropriate access to prescribed opioids, assess opioid-taking behavior, provide education regarding storage and disposal, and implement educational interventions accordingly.

The Use of Telehealth to Provide Continuity of Cancer Care during the COVID-19 Pandemic: Advantages, Disparities, and Implications to Promote Health Equity.

Perceptions of oncology health care providers use of telehealth to provide care to patients during the COVID-19 pandemic were explored. A qualitative study using semi-structured interviews and purposive sampling (N = 30) was conducted. Four themes emerged: 1) telehealth provided continuity of cancer care and used to decrease the risk of COVID-19 exposure; 2) advantages brought about convenience and inclusion of family caregivers; 3) telehealth revealed geographic, aging, and racial/ethnic disparities and digital illiteracy; and 4) rapid implementation was challenging. Telehealth provides a number of opportunities to support care for vulnerable cancer patients during this health crisis; however, disparities must be addressed.

Leisure-time physical activity, anthropometrics, and body composition as predictors of quality of life domains after spinal cord injury: an exploratory cross-sectional study.

The objective of the current work was to examine the relationships between quality of life (QOL) domains in persons with spinal cord injury (SCI) and their levels of weekly leisure-time physical activity (LTPA), anthropometric variables, and body composition variables. This exploratory cross-sectional study consisted of baseline data collected as part of a randomized clinical trial at a VA Medical Center and SCI center. A convenience sample of 36 community-dwelling persons with SCI participated in the current study. Outcome measures included the World Health Organization Quality of Life Short Form (WHOQOL-BREF), Leisure-Time Physical Activity Questionnaire for People with Spinal Cord Injury (LTPAQ-SCI), anthropomorphic measures (waist, hip, and abdominal circumference), and dual-energy x-ray absorptiometry (DXA) to quantify regional and total body composition. Multiple regression models suggested that engagement in LTPA accounted for 35.7% of the variance in physical health QOL, 33.5% in psychological QOL, 14.2% in social relationships QOL, and 38.2% in environmental QOL. Anthropometric measures accounted for 11.3%, 3.1%, 12.0%, and 6.7% of the variance in these QOL indices, respectively, and DXA indices accounted for 18.7%, 17.5%, 27.4%, and 21.9%. Within these models, the number of minutes of heavy LTPA per day uniquely predicted physical health QOL, the number of mild LTPA days per week uniquely predicted psychological QOL, and the amount of mild LTPA per day uniquely predicted environmental QOL. Bivariate analyses also suggested that android and trunk fat, as well as supine waist and abdominal circumferences, were positively associated with social relationships QOL. Encouraging individuals with SCI to engage in LTPA may robustly enhance multiple aspects of QOL while reducing the risk for cardiovascular and metabolic morbidities associated with SCI. Moreover, this may lead to a further understanding of how QOL may impact longitudinal intervention trials. The study protocol and procedures were reviewed and approved by the McGuire VA Research Institutional Review Board (IRB# 02152, approval date August 9, 2015; IRB# 02375, approval date May 2, 2018).

Subcortical brain structure in children with developmental coordination disorder: A T1-weighted volumetric study.

Developmental coordination disorder (DCD) is a neurodevelopmental disorder occurring in 5-6% of school-aged children. Converging evidence suggests that dysfunction within cortico-striatal and cortico-cerebellar networks may contribute to motor deficits in DCD, yet limited research has examined the brain morphology of these regions. Using T1-weighted magnetic resonance imaging the current study investigated cortical and subcortical volumes in 37 children with DCD, aged 8 to 12 years, and 48 controls of a similar age. Regional brain volumes of the thalamus, basal ganglia, cerebellum and primary motor and sensory cortices were extracted using the FreeSurfer recon-all pipeline and compared between groups. Reduced volumes within both the left and right pallidum (Left: F = 4.43, p = 0.039; Right: F = 5.24, p = 0.025) were observed in children with DCD; however, these results did not withstand correction for multiple comparisons. These findings provide preliminary evidence of altered subcortical brain structure in DCD. Future studies that examine the morphology of these subcortical regions are highly encouraged in order replicate these findings.

Improving Electronic Survey Response Rates Among Cancer Center Patients During the COVID-19 Pandemic: Mixed Methods Pilot Study.

BACKGROUND: Surveys play a vital role in cancer research. During the COVID-19 pandemic, the use of electronic surveys is crucial to improve understanding of the patient experience. However, response rates to electronic surveys are often lower compared with those of paper surveys. OBJECTIVE: The aim of this study was to determine the best approach to improve response rates for an electronic survey administered to patients at a cancer center during the COVID-19 pandemic. METHODS: We contacted 2750 patients seen at Moffitt Cancer Center in the prior 5 years via email to complete a survey regarding their experience during the COVID-19 pandemic, with patients randomly assigned to a series of variations of prenotifications (ie, postcard, letter) or incentives (ie, small gift, modest gift card). In total, eight combinations were evaluated. Qualitative interviews were conducted to understand the level of patient understanding and burden with the survey, and quantitative analysis was used to evaluate the response rates between conditions. RESULTS: A total of 262 (9.5%) patients completed the survey and 9 participated in a qualitative interview. Interviews revealed minimal barriers in understanding or burden, which resulted in minor survey design changes. Compared to sending an email only, sending a postcard or letter prior to the email improved response rates from 3.7% to 9.8%. Similarly, inclusion of an incentive significantly increased the response rate from 5.4% to 16.7%, especially among racial (3.0% to 12.2%) and ethnic (6.4% to 21.0%) minorities, as well as among patients with low socioeconomic status (3.1% to 14.9%). CONCLUSIONS: Strategies to promote effective response rates include prenotification postcards or letters as well as monetary incentives. This work can inform future survey development to increase response rates for electronic surveys, particularly among hard-to-reach populations.