Diabetes Screening by Race and Ethnicity in the United States: Equivalent Body Mass Index and Age Thresholds.

BACKGROUND: Racial/ethnic minority populations in the United States have increased rates of diabetes compared with White populations. The 2021 guidelines from the U.S. Preventive Services Task Force recommend diabetes screening for adults aged 35 to 70 years with a body mass index (BMI) of 25 kg/m2 or greater. OBJECTIVE: To determine the BMI threshold for diabetes screening in major racial/ethnic minority populations with benefits and harms equivalent to those of the current diabetes screening threshold in White adults. DESIGN: Cross-sectional study. SETTING: NHANES (National Health and Nutrition Examination Survey), 2011 to 2018. PARTICIPANTS: Nonpregnant U.S. adults aged 18 to 70 years (n = 19 335). MEASUREMENTS: A logistic regression model was used to estimate diabetes prevalence at various BMIs for White, Asian, Black, and Hispanic Americans. For each racial/ethnic minority group, the equivalent BMI threshold was defined as the BMI at which the prevalence of diabetes in 35-year-old persons in that group is equal to that in 35-year-old White adults at a BMI of 25 kg/m2. Ranges were estimated to account for the uncertainty in prevalence estimates for White and racial/ethnic minority populations. RESULTS: Among adults aged 35 years with a BMI of 25 kg/m2, the prevalence of diabetes in Asian Americans (3.8% [95% CI, 2.8% to 5.1%]), Black Americans (3.5% [CI, 2.7% to 4.7%]), and Hispanic Americans (3.0% [CI, 2.1% to 4.2%]) was significantly higher than that in White Americans (1.4% [CI, 1.0% to 2.0%]). Compared with a BMI threshold of 25 kg/m2 in White Americans, the equivalent BMI thresholds for diabetes prevalence were 20 kg/m2 (range, <18.5 to 23 kg/m2) for Asian Americans, less than 18.5 kg/m2 (range, <18.5 to 23 kg/m2) for Black Americans, and 18.5 kg/m2 (range, <18.5 to 24 kg/m2) for Hispanic Americans. LIMITATION: Sample size limitations precluded assessment of heterogeneity within racial/ethnic groups. CONCLUSION: Among U.S. adults aged 35 years or older, offering diabetes screening to Black Americans and Hispanic Americans with a BMI of 18.5 kg/m2 or greater and Asian Americans with a BMI of 20 kg/m2 or greater would be equivalent to screening White adults with a BMI of 25 kg/m2 or greater. Using screening thresholds specific to race/ethnicity has the potential to reduce disparities in diabetes diagnosis. PRIMARY FUNDING SOURCE: Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology.

Prevalence and predictors of mood disturbances in idiopathic REM sleep behaviour disorder.

Depression and anxiety are commonly associated with synucleinopathies. Mood disturbances have also been reported in patients with idiopathic REM sleep behaviour disorder (iRBD) and are difficult to treat due to exacerbation of sleep symptoms with standard antidepressants. Despite this, detailed prevalence studies of mood symptomatology and contributors to mood disturbances in iRBD are limited. Mood, sleep, autonomic, cognitive and motor symptoms were assessed in 49 well-characterized patients with iRBD using a variety of clinical scales. Spearman correlations, factor analysis and multiple linear regression were used to uncover associations between mood and non-motor and motor symptoms. The prevalence of significant depression was 17.0% and that of anxiety was 14.6% in the iRBD cohort. Age and disease duration were not correlated with these affective symptoms in iRBD patients. We found depression was significantly predicted by the presence and severity of motor, sleep and cognitive symptoms. Anxiety was predicted by the severity of nocturnal and daytime sleep-related symptoms, cognitive symptoms and autonomic symptoms, with a differential effect depending on the questionnaire used. Depression and anxiety are common in iRBD patients and can be significantly explained by specific sets of non-motor and motor symptoms. These associations provide insight into the underlying pathophysiology and emphasize the importance of a holistic approach to mood disturbance in this population, which may circumvent the reliance on pharmacotherapy that can exacerbate dream enactment behaviour.

Prevalence of angina and use of medical therapy among US adults: A nationally representative estimate.

Recent results from the ISCHEMIA trial highlight the importance of medical management for patients with stable ischemic heart disease. We determine the prevalence of angina in the United States, as well as the use of first-line goal directed therapy by US patients with angina. We used individual patient level data from the National Health and Nutrition Examination Survey (NHANES), 2007-2016. Using the complex survey weights, we create projections for the US population with angina as well as those using ß-blockers, antiplatelet agents, or statins-3 first-line medications for patients with angina. Among adults ≥40 years old, 4,469,934 US adults are estimated to have physician-diagnosed angina. Of the patients with angina, 2,757,171 (61.7%) were on ß-blockers, 2,984,902 (66.8%) were on statins, and 2,433,088 (54.4%) were on any antiplatelet medication; 1,457,983 patients were on all 3 medications, for an overall proportion of 32.6% of angina patients taking all three first-line medications in the United States. While the prevalence of angina in the US is high, the use of goal-directed medical therapy remains low. Strategies to improve the use of medications for preventing secondary events are urgently needed.

Enteral and parenteral nutrition in cancer patients, a comparison of complication rates: an updated systematic review and (cumulative) meta-analysis.

INTRODUCTION: Weight loss in cancer patients is a worrisome constitutional change predicting disease progression and shortened survival time. A logical approach to counter some of the weight loss is to provide nutritional support, administered through enteral nutrition (EN) or parenteral nutrition (PN). The aim of this paper was to update the original systematic review and meta-analysis previously published by Chow et al., while also assessing publication quality and effect of randomized controlled trials (RCTs) on the meta-conclusion over time. METHODS: A literature search was carried out; screening was conducted for RCTs published in January 2015 up until December 2018. The primary endpoints were the percentage of patients achieving no infection and no nutrition support complications. Secondary endpoints included proportion of patients achieving no major complications and no mortality. Review Manager (RevMan 5.3) by Cochrane IMS and Comprehensive Meta-Analysis (version 3) by Biostat were used for meta-analyses of endpoints and assessment of publication quality. RESULTS: An additional seven studies were identified since our prior publication, leading to 43 papers included in our review. The results echo those previously published; EN and PN are equivalent in all endpoints except for infection. Subgroup analyses of studies only containing adults indicate identical risks across all endpoints. Cumulative meta-analysis suggests that meta-conclusions have remained the same since the beginning of publication time for all endpoints except for the endpoint of infection, which changed from not favoring to favoring EN after studies published in 1997. There was low risk of bias, as determined by assessment tool and visual inspection of funnel plots. CONCLUSIONS: The results support the current European Society of Clinical Nutrition and Metabolism guidelines recommending enteral over parenteral nutrition, when oral nutrition is inadequate, in adult patients. Further studies comparing EN and PN for these critical endpoints appear unnecessary, given the lack of change in meta-conclusion and low publication bias over the past decades.

Correction to: Enteral and parenteral nutrition in cancer patients, a comparison of complication rates: an updated systematic review and (cumulative) meta-analysis.

The appendices were incorrectly numbered in the original article. Please see below correcct appendices.

Diagnostic Imaging Modalities to Assess Treatment Response of Bone Metastasis in Patients Receiving Palliative Radiotherapy: A Scoping Review of the Literature.

PURPOSE: Several studies have used objective radiologic data to assess the effect of palliative radiotherapy on tumor burden. The purpose of this literature review was to survey the various metrics that have been used to quantify bone tumor response to palliative radiotherapy by radiographical means and to determine whether any of these metrics were associated with clinical palliative outcomes. METHODS: In accordance with PRISMA extension for Scoping Reviews guidelines, a literature search Ovid Medline and OldMedline from 1946 to February 6, 2019, Embase Classic/Embase from 1947 to 2019 week 5, and Cochrane Central Register of Controlled Trials February 2019 to extract articles related to quantified radiologic evaluation of bone metastases following palliative radiotherapy. Imaging modality, quantification metric, and association between imaging modality and clinical response were recorded. RESULTS: Fourteen articles selected for full-text review utilized computed tomography (10 studies), fluorodeoxyglucose-positron emission tomography (3 studies), magnetic resonance imaging (1 study), diffusion-weighted magnetic resonance imaging (3 studies), and X-ray (1 study) imaging modalities. Variables assessed included tumor volume regression, bone density, metabolic activity, and signal intensity. Studies differed both in the type of imaging modality used and metric derived to quantify the radiologic findings. Fifty percent of the included studies aimed to identify a relationship between a quantified radiologic metric and clinical palliative response. Of these studies, 86% reported a correlation. CONCLUSION: Quantified radiologic metrics can provide an objective measure of response to palliative radiotherapy and may be useful in predicting clinical palliative response. More studies are needed to validate these metrics and develop a standardized protocol for radiologic evaluation that can be implemented into a clinical workflow.

Compliance monitoring via a Bluetooth-enabled retainer: A prospective clinical pilot study.

OBJECTIVES: To conduct a prospective pilot trial to test the clinical efficacy and accuracy of a newly developed Bluetooth-enabled retainer, which was synchronized with an iOS mobile application, cloud database and provider webpage. SETTING AND SAMPLE POPULATION: Five orthodontic residents in a university setting. MATERIAL AND METHODS: At the delivery of the retainers (T0), each participant was given an Bluetooth-enabled retainer, logbook and iPod Touch installed with the mobile application. Participants were instructed to wear the retainer for 12 hours per day and record in the logbook each time the retainer was inserted or removed and trained to synchronize the device daily to the mobile application. After the 5-day study period (T1), statistical analysis was performed comparing the device-reported data to the logbook data using two calculation methods. RESULTS: From T0 - T1, the participants wore their retainers for a median of 11.55 hours per day and the median difference between the self-reported (logbook) data and the device data was 35 minutes or 5.1% over the 5-day study period. Using an adjusted method to calculate the device-reported wear time, the median error was 13 minutes or 1.9%. CONCLUSION: Subjects were able to successfully wear the retainer and upload the data to the mobile application and cloud database. Patient compliance and technical issues could be monitored daily via the provider webpage, and early intervention was possible with reminder messaging. The Bluetooth-enabled retainer showed a clinically acceptable level of accuracy and usability that validates it for future clinical testing.

A prospective study of docetaxel-associated pain syndrome.

PURPOSE: To investigate the natural history of taxane-associated acute pain syndrome (TAPS) in a docetaxel patient cohort and to examine the long-term manifestation of TAPS. PATIENTS AND METHODS: For three consecutive treatment cycles, taxane-naive breast cancer patients completed diaries on days 1-7, 14, and 21 and telephone questionnaires 1, 3, 6, 9, and 12 months following treatment. Questionnaires to assess pain and interference were adapted from the Brief Pain Inventory. To examine the experience of arthralgia and myalgia as one syndrome, information on patient experiences with arthralgia or myalgia was elicited separately in order to determine how closely experiences of each toxicity correlated with each other. A ≥2 point increase from baseline was defined as an arthralgia or myalgia "pain flare," and only those with "flare" were included in calculations of incidence. RESULTS: A total of 278 patients were accrued. Thirty-eight patients were omitted due to missing information, and 24 patients were omitted due to metastatic disease, for a total of 216 patients overall and 188 in the docetaxel cohort. A total of 74.5% of docetaxel patients experienced joint pain flare, and 78.2% experienced muscle pain flare at some point in the overall course of three treatment cycles. Joint and muscle pain peaked on days 4-5 for each cycle, and median pain severity for both joint and muscle pain was 4/10 during the 21-day period. Median onset of joint pain flare was 3 days for cycle 1 and 4 days for cycles 2 and 3, with an average median duration of 4 days. Median onset of muscle pain flare was 4 days for all three cycles, with a median duration of 4 days for cycles 1 and 2, and 5 days for cycle 3. Both joint and muscle pain persisted 1 year after treatment in approximately half of responding patients. CONCLUSION: This study documents the significant incidence of TAPS in patients treated with docetaxel chemotherapy and shows a long-term persistence of the syndrome.

Low-Density Lipoprotein Cholesterol Levels in Adults With Coronary Artery Disease in the US, January 2015 to March 2020.

This study uses National Health and Nutrition Examination Survey data to examine lipid control among adults in the US with coronary artery disease from January 2015 to March 2020.

Taxane-induced arthralgia and myalgia: A literature review.

Purpose Arthralgia and myalgia following taxane chemotherapy has been documented in the literature. However, these two toxicities associated with taxane treatment have not been closely examined in the literature, and data remain inconsistent in terms of the reported incidences of these toxicities. The purpose of this literature review was to provide a more comprehensive understanding of the incidence of taxane-induced arthralgia and myalgia, as well as to document the risk factors and preventative and therapeutic treatments that have been investigated. Methods A literature search was conducted in Ovid Medline, OldMedline, Embase, Embase Classic, and Cochrane Central Register of Controlled Trials using relevant subject headings and keywords such as: "arthralgia," "myalgia," "muscle pain," "joint pain," "taxane," "chemotherapy," "docetaxel," "paclitaxel." Results The reported incidences of arthralgia and myalgia were variable. Taxane chemotherapy was found to be associated with greater incidences of arthralgia and myalgia than non-taxane forms of chemotherapy. Moreover, docetaxel and nab-paclitaxel seem to be associated with lower incidences of arthralgia and myalgia than paclitaxel. Finally, the literature on prevention and therapeutic treatment of taxane-induced arthralgia and myalgia is scarce. Conclusion More studies should be done in order to more conclusively identify optimal therapeutic and preventative treatments as well as different risk factors. We recommend that a prospective study be done in order to better understand the true incidence of arthralgia and myalgia in patients being treated with the paclitaxel, docetaxel, and nab-paclitaxel.

Efficacy and safety of olanzapine for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) as reported in phase I and II studies: a systematic review.

INTRODUCTION: Olanzapine is an atypical antipsychotic drug that inhibits serotonergic, dopaminergic, alpha-1 adrenergic, histaminic, and muscarinic receptors. Several phase I and II trials have been published documenting the use of olanzapine in controlling chemotherapy-induced nausea and vomiting (CINV). This review aims to summarize all phase I and II trials that reported on olanzapine for the prophylaxis of CINV. METHODS: A literature search was conducted in Ovid MEDLINE from 1946 to July week 1 2015, Embase Classic and Embase from 1947 to 2015 week 28, and the Cochrane Central Register of Controlled Trials up until June 2015. Phase I and II trials reporting on olanzapine for the prophylaxis for CINV were included if they reported on at least one of four primary endpoints: complete response (CR), complete control (CC), no nausea, and no emesis. Other endpoints of interest included the safety of olanzapine as measured by the M.D. Anderson Symptom Inventory. RESULTS: Across the seven included studies, there were a total of 201 patients. The CR across four studies was 97.2, 83.1, and 82.8 % for the acute, delayed, and overall phases, respectively. The CC for acute, delayed, and overall phases was 92.5, 87.5, and 82.5 %, respectively. The overall no nausea rate was 92.7, 71.8, and 70.6 % for the acute, delayed, and overall phases, respectively. The overall no emesis rates for the acute, delayed, and overall phases were 100, 94.5, and 90.4 %, respectively. Fatigue, drowsiness, and disturbed sleep were common side effects. CONCLUSION: Olanzapine is efficacious and safe when used as a prophylaxis for CINV.

Symptoms and quality of life in patients with brain metastases receiving whole-brain radiation therapy.

PURPOSE: Patients with multiple brain metastases may be treated with whole-brain radiation therapy (WBRT). For these patients, symptom palliation and improvement of quality of life (QOL) and performance status is of the upmost importance. The objective of the present study was to determine the symptom experience and overall QOL in patients with brain metastases before and after WBRT. METHODS: A total of 14 symptom scores and overall QOL were collected prospectively in 217 patients for up to 3 months. Wilcoxon signed rank test was applied to determine significant symptoms and QOL changes. Spearman's correlations were applied to determine the relationship between symptom scores and QOL. RESULTS: Appetite loss, weakness, and nausea significantly increased from baseline, while balance, headache, and anxiety significantly decreased from baseline. At baseline, all symptoms other than coordination were significantly correlated with QOL. At 1-month follow-up (FU), changes in concentration, weakness, coordination, and balance were significantly associated with QOL changes. At 2-month FU, changes in pain, insomnia, concentration, balance, and depression were significantly associated with QOL changes. At 3-month FU, only change in nausea was significantly associated with QOL changes. CONCLUSIONS: Following WBRT, certain symptoms may influence overall QOL to a greater extent than others, which may fluctuate with time.

Efficacy of olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis.

PURPOSE: Olanzapine is a potent antipsychotic medication that inhibits a wide variety of receptors. It has been used in trials for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV). This study systematically investigates the efficacy of olanzapine in relation to other antiemetics in the prophylaxis and rescue of CINV. METHODS: A literature search of Ovid MEDLINE, EMBASE, and CENTRAL was conducted to identify randomized controlled trials (RCTs) comparing olanzapine to other standard antiemetics for either prevention or rescue. The primary endpoints were the percentage of patients achieving no emesis or no nausea, in the acute, delayed, and overall phases. RESULTS: Ten RCTs in the preventative setting and three RCTs in the breakthrough setting were identified. Subgroup analysis demonstrated a similar degree of benefit from a 5- and 10-mg dose of olanzapine for the no emesis endpoint in the overall phase. In the prophylaxis setting, olanzapine was statistically superior in five of six endpoints and clinically superior in four of six endpoints. In the breakthrough setting, olanzapine was statistically and clinically superior in the only endpoint analyzed: no emesis. CONCLUSION: Olanzapine is more efficacious than other standard antiemetics for the rescue of CINV and its inclusion improves control in the prevention setting. Given the possible reduction in side effects, the use of a 5-mg dose of olanzapine should be considered. Future RCTs should compare the 5-mg versus the 10-mg dosages further and report on the efficacy and percentage of patients developing side effects. Further analyses should be done without the influence of corticosteroids.

Which pain intensity scale from the Brief Pain Inventory correlates most highly with functional interference scores in patients experiencing taxane-induced arthralgia and myalgia?

PURPOSE: The purpose of this study was to assess which pain intensity dimension scale (worst, least, average, or current pain) from the Brief Pain Inventory (BPI) correlates most highly with functional interference scores in patients experiencing taxane-induced arthralgia and myalgia. METHODS: Breast cancer patients scheduled to receive docetaxel, paclitaxel, or albumin-bound paclitaxel (nab-paclitaxel) were enrolled in the study. Patients completed an initial baseline questionnaire and subsequently filled out a diary based on the BPI on days 1-7, 14, and 21 for three consecutive treatment cycles. Pain scores for worst, least, average, and current pain intensity dimensions as well as pain interference scores were recorded in the diaries and questionnaires using the BPI. Worst, least, average, and current pain scores were correlated with functional pain interference scores using Spearman's rank correlation coefficients. A general linear mixed model of each functional interference measure was performed over time for cycles 1-3 with each pain intensity dimension scale. RESULTS: Among worst, average, least, and current joint pain dimensions, average joint pain scores correlated best with all BPI interference responses while average muscle pain scores correlated best with all BPI interference responses except for sleeping probability and normal work. CONCLUSION: We recommend the BPI scale measuring average pain for future studies evaluating pain scores in patients experiencing taxane-induced arthralgia and myalgia.

Inadequacy of Palliative Training in the Medical School Curriculum.

This report examines the literature on palliative training in the current medical school curriculum. A literature search was conducted to identify relevant articles. Physicians and medical students both report feeling that their training in end-of-life care and in palliative issues is lacking. The literature expresses concerns about the varied and non-uniform approach to palliative care training across medical schools. The authors recommend the development of more palliative training assessment tools in order to aid in the standardization of curriculum involving end-of-life care. In addition, increased exposure to dying patients will aid students in building comfort with palliative care issues. Such a goal may be accomplished through required clerkships or other similar programs.

The impact of clinical and sociodemographic features on quality of life in patients with early stage cancers using the Functional Assessment of Cancer Therapy-General assessment tool.

PURPOSE: This study aims to compare the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life (QOL) scores of patient groups with varying clinical and sociodemographic features in the early stage cancer population. METHODS: A literature search was conducted on both the Embase and OvidSP platforms. Weighted analysis of variance (ANOVA) was performed for binary predictors and weighted linear regression analysis was conducted for continuous predictors. RESULTS: Six binary features predicted at least one domain of QOL: primary cancer site (homogeneous versus heterogeneous), total per capita healthcare expenditures, mean age, previous chemotherapy, radiotherapy, and previous hormonal therapy. Two continuous factors had predictive value with respect to QOL: completion of postsecondary education and marital status. CONCLUSION: Although there are limitations of the current study, similar correlations to our own have been previously described between QOL and healthcare expenditures, mean age and education. Currently, the literature conflicts in its analysis of previous radiotherapy and chemotherapy as predictors of QOL. No published evidence exists describing the presently found relationships in primary cancer site, marital status and hormonal therapy. Future work may focus on determining cause and effect relationships between these predictors and QOL.

Trends in Blood Pressure Treatment Intensification in Older Adults With Hypertension in the United States, 2008 to 2018.

BACKGROUND: Hypertension control has worsened nationally, and treatment intensification is important for control. National trends for appropriate blood pressure intensification for older adults are unknown. We determine the proportion of ambulatory visits where older adults with hypertension were appropriately intensified on antihypertensives from 2008 to 2018. METHODS: Data from National Ambulatory Medical Care Survey were used. National Ambulatory Medical Care Survey is a nationally representative sample of ambulatory visits. Adults 60 years or older were included. Appropriate antihypertensive intensification was defined as addition of an antihypertensive for a blood pressure reading above target. We examined appropriate intensification by blood pressure targets set by the American College of Cardiology-American Heart Association, the European Society of Cardiology, and the American College of Physicians-American Academy of Family Physicians guidelines for older adults. Further, we defined an additional all-inclusive criterion meeting all 3 guidelines. RESULTS: From 2008 to 2018, appropriate intensification by American College of Cardiology/American Heart Association occurred at 11.1% (95% CI, 9.8%-12.5%) of visits, decreasing from 13.6% (95% CI, 15.6%-28.7%) of visits in 2008 to 2009 to 10.4% (95% CI, 10.9%-26.4%) in 2015 to 2018. Appropriate intensification by European Society of Cardiology occurred at 14.2% (12.1%-16.6%) of visits over 2008 to 2018, decreasing from 16.9% (95% CI, 13.5%-21.0%) in 2008 to 2009 to 12.5% (95% CI, 7.4%-20.3%) from 2015 to 2018. Appropriate intensification by American Academy of Family Physicians/American College of Physicians occurred at 18.9% (16.2%-22.0%) of visits over 2008 to 2018, decreasing from 24.7% (95% CI, 20.2%-29.0%) in 2008 to 2009 to 14.9% (95% CI, 9.0%-23.7%) from 2015 to 2018. By all-inclusive criteria, intensification trended toward worsening with time: odds ratio: 0.93 ([95% CI, 0.87-1.00]; P=0.07). CONCLUSIONS: Appropriate treatment intensification for older adults with hypertension in the United States was suboptimal over the past decade.

Dimensional structure of one-year post-COVID-19 neuropsychiatric and somatic sequelae and association with role impairment.

This study examined the latent structure of the broad range of complex neuropsychiatric morbidities occurring 1 year after COVID-19 infection. As part of the CU-COVID19 study, 248 (response rate=39.3%) of 631 adults hospitalized for COVID-19 infection in Hong Kong completed an online survey between March-2021 and January-2022. Disorder prevalence was compared against a random non-infected household sample (n=1834). 248 surveys were received on average 321 days post-infection (Mean age: 48.9, 54% female, moderate/severe/critical infection: 58.2%). 32.4% were screened to have at least one mental disorder, 78.7% of whom had concurrent fatigue/subjective cognitive impairment (SCI). Only PTSD (19.1%) was significantly more common than control (14%, p=0.047). Latent profile analysis classified individuals into P1 (12·4%)-no current neuropsychiatric morbidities, P2 (23.1%)-SCI/fatigue, P3 (45.2%)-anxiety/PTSD, P4 (19.3%)-depression. SCI and fatigue pervaded in all profiles (P2-4) with neuropsychiatric morbidities one-year post-infection. PTSD, anxiety and depressive symptoms were most important in differentiating P2-4. Past mental health and P4 independently predicted functional impairment. Neuropsychiatric morbidity was associated with past mental health, reduced resilience, financial problems, but not COVID-19 severity. Their confluence with depressive and anxiety symptoms predicted impairment and are associated with psychological and environmental factors.

Identifying the core genome of the nucleus-forming bacteriophage family and characterization of Erwinia phage RAY.

We recently discovered that some bacteriophages establish a nucleus-like replication compartment (phage nucleus), but the core genes that define nucleus-based phage replication and their phylogenetic distribution were still to be determined. Here, we show that phages encoding the major phage nucleus protein chimallin share 72 conserved genes encoded within seven gene blocks. Of these, 21 core genes are unique to nucleus-forming phage, and all but one of these genes encode proteins of unknown function. We propose that these phages comprise a novel viral family we term Chimalliviridae. Fluorescence microscopy and cryoelectron tomography studies of Erwinia phage vB_EamM_RAY confirm that many of the key steps of nucleus-based replication are conserved among diverse chimalliviruses and reveal variations on this replication mechanism. This work expands our understanding of phage nucleus and PhuZ spindle diversity and function, providing a roadmap for identifying key mechanisms underlying nucleus-based phage replication.

Identifying the core genome of the nucleus-forming bacteriophage family and characterization of Erwinia phage RAY.

We recently discovered that some bacteriophages establish a nucleus-like replication compartment (phage nucleus), but the core genes that define nucleus-based phage replication and their phylogenetic distribution were unknown. By studying phages that encode the major phage nucleus protein chimallin, including previously sequenced yet uncharacterized phages, we discovered that chimallin-encoding phages share a set of 72 highly conserved genes encoded within seven distinct gene blocks. Of these, 21 core genes are unique to this group, and all but one of these unique genes encode proteins of unknown function. We propose that phages with this core genome comprise a novel viral family we term Chimalliviridae. Fluorescence microscopy and cryo-electron tomography studies of Erwinia phage vB_EamM_RAY confirm that many of the key steps of nucleus-based replication encoded in the core genome are conserved among diverse chimalliviruses, and reveal that non-core components can confer intriguing variations on this replication mechanism. For instance, unlike previously studied nucleus-forming phages, RAY doesn't degrade the host genome, and its PhuZ homolog appears to form a five-stranded filament with a lumen. This work expands our understanding of phage nucleus and PhuZ spindle diversity and function, providing a roadmap for identifying key mechanisms underlying nucleus-based phage replication.