In humans, homologous to the E6-AP carboxyl terminus (HECT) and regulator of chromosome condensation 1 (RCC1)-like domain-containing protein 5 (HERC5) is an interferon-induced protein that inhibits replication of evolutionarily diverse viruses, including human immunodeficiency virus type 1 (HIV-1). To better understand the origin, evolution, and function of HERC5, we performed phylogenetic, structural, and functional analyses of the entire human small-HERC family, which includes HERC3, HERC4, HERC5, and HERC6. We demonstrated that the HERC family emerged >595 million years ago and has undergone gene duplication and gene loss events throughout its evolution. The structural topology of the RCC1-like domain and HECT domains from all HERC paralogs is highly conserved among evolutionarily diverse vertebrates despite low sequence homology. Functional analyses showed that the human small HERCs exhibit different degrees of antiviral activity toward HIV-1 and that HERC5 provides the strongest inhibition. Notably, coelacanth HERC5 inhibited simian immunodeficiency virus (SIV), but not HIV-1, particle production, suggesting that the antiviral activity of HERC5 emerged over 413 million years ago and exhibits species- and virus-specific restriction. In addition, we showed that both HERC5 and HERC6 are evolving under strong positive selection, particularly blade 1 of the RCC1-like domain, which we showed is a key determinant of antiviral activity. These studies provide insight into the origin, evolution, and biological importance of the human restriction factor HERC5 and the other HERC family members.IMPORTANCE Intrinsic immunity plays an important role as the first line of defense against viruses. Studying the origins, evolution, and functions of proteins responsible for effecting this defense will provide key information about virus-host relationships that can be exploited for future drug development. We showed that HERC5 is one such antiviral protein that belongs to an evolutionarily conserved family of HERCs with an ancient marine origin. Not all vertebrates possess all HERC members, suggesting that different HERCs emerged at different times during evolution to provide the host with a survival advantage. Consistent with this, two of the more recently emerged HERC members, HERC5 and HERC6, displayed strong signatures of having been involved in an ancient evolutionary battle with viruses. Our findings provide new insights into the evolutionary origin and function of the HERC family in vertebrate evolution, identifying HERC5 and possibly HERC6 as important effectors of intrinsic immunity in vertebrates.

The Society of Nuclear Medicine and Molecular Imaging (SNMMI), founded in 1954, is an international scientific and professional organization with a purpose to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM), founded in 1985, is a nonprofit professional medical association with a purpose to facilitate international communication among individuals in nuclear medicine pursuing clinical and academic excellence. Members of the SNMMI and EANM are physicians, technologists, and scientists who specialize in the research and practice of nuclear medicine. The SNMMI and EANM will periodically publish new guidelines for nuclear medicine practice to further advance the science of nuclear medicine and improve patient care. Existing standards/guidelines will be reviewed for revision or renewal, as appropriate. Each standard/guideline, representing a policy statement by the SNMMI/EANM, has undergone a thorough review, and represents an expert consensus. The SNMMI and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging requires specific training and skills, as described in each document. These standards/guidelines are educational resources designed to assist practitioners in providing appropriate nuclear medicine care for patients. They are consensus documents, and are not mandatory provisions or requirements of practice. They are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the SNMMI and the EANM cautions against the use of these standards/guidelines in litigation procedures that call into question the clinical decisions of a practitioner. The ultimate judgment regarding the appropriateness and propriety of any specific procedure or course of action must be made by medical professionals, taking into account the unique context of each case. Thus, there is no implication that action differing from what is detailed in these standards/guidelines, on its own, is below the standard of care. On the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the standards/guidelines when, based on the reasonable judgment of the practitioner, such course of action is warranted based on the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the standards/guidelines. Practicing medicine involves not only the science, but also the art of dealing with the prevention, detection, diagnosis, and treatment of disease. The variety and complexity of human conditions make it impossible for general guidelines to consistently allow for an accurate diagnosis to be reached or a specific treatment response to be predicted. Therefore, it should be recognized that adhering to these standards/guidelines does not ensure a successful outcome. All that should be expected is that a practitioner follows a reasonable course of action based on their level of training, the current landscape of knowledge, the resources at their disposal, and the needs/context of the particular patient being treated. The purpose of this document is to provide nuclear medicine physicians, radiologists, and other clinicians with guidelines for the recommendation, performance and interpretation of 99mTc-dimercaptosuccinic acid renal cortical scintigraphy ([99mTc] Tc-DMSA scintigraphy) in pediatric patients. These recommendations represent the expert opinions of experienced leaders in this field, and these recommendations are not all supported by a high level of evidence. Further studies are required to have evidence-based recommendations for the application of [99mTc] Tc-DMSA renal cortical scintigraphy in pediatrics. This guideline summarizes the views of the SNMMI Renal Cortical Scintigraphy in Children Working Group and the EANM Pediatrics Committee. It reflects recommendations for which the SNMMI and EANM cannot be held responsible. The recommendations should be taken into context of good practice of nuclear medicine and do not substitute for national and international legal or regulatory provisions.

Elder abuse is an underdetected, under-reported issue with severe consequences. Its detection presents unique challenges based on characteristics of this vulnerable population, including cognitive impairment, age-related deconditioning, and an increased number of co-morbidities, all of which predispose to increase vulnerability to injury. While radiologists play a critical role in detection of child abuse, this role is currently not paralleled in detection of elder abuse. We conducted a thorough review of the literature using MEDLINE to describe the current knowledge on injury patterns and injury findings seen in elder abuse, as well as barriers to and recommendations for an increased role of diagnostic imaging in elder abuse detection. Barriers limiting the role of radiologists include lack of training and paucity of rigorous systematic research delineating distinctive imaging findings for physical elder abuse. We outline the current ways in which imaging can help raise clinical suspicion for elder abuse, including inconsistencies between purported mechanism of injury and imaging findings, injury location, multiple injuries at differing stages of healing, and particular patterns of injury likely to be intentionally inflicted. We additionally outline the mechanism by which medical education and clinical workflow may be modified to increase the role for imaging and radiologist participation in detecting abuse in older adult patients, and identify potential future directions for further systematic research.

The current study endeavored to closely compare the detection rate of 68-Gallium labelled prostate-specific membrane antigen ([68Ga]Ga-PSMA) versus [18F]Fluorocholine in men with prostate cancer (PC), to investigate the benefits and pitfalls of each modality in the setting of various patient characteristics. We retrospectively analyzed 29 biopsy-proven PC patients in two categories, staging and restaging, who underwent both scans within a maximum of 30 days of each other. Variables including patient demographics, prostate specific antigen (PSA) level, Gleason score, clinical course, and following treatments were recorded. The number and location of suspicious lesions as well as uptake values were noted. A total of 148 suspicious lesions were detected, of which 70.9% (105/148) were concordantly visualized in both imaging modalities. [68Ga]Ga-PSMA positron emission tomography/computed tomography (PET/CT) revealed a higher number of metastatic lesions per patients (91% vs 78%). The mean of maximum standardized uptake value (SUV max) in concordant lesions was significantly higher in [68Ga]Ga-PSMA compared to [18F]Fluorocholine PET/CT (14.6 ± 8.44 vs. 6.9 ± 3.4, p = 0.001). Discordant lesions were detected by both modalities, but more frequently by [68Ga]Ga-PSMA PET/CT (20.3% in [68Ga]Ga-PSMA versus 8.8% by [18F]Fluorocholine PET/CT). In patients with PSA levels below 1.0 ng/mL and <2.0 ng/mL, [18F]Fluorocholine PET/CT detection rate was half (57% and 55%, respectively) that of [68Ga]Ga-PSMA PET/CT. Tumor, nodes and metastases (TNM) staging, and subsequently patient management, was only influenced in 4/29 patients (14%), particularly by [68Ga]Ga-PSMA PET/CT with PSA values under 0.5 ng/mL. [68Ga]Ga-PSMA PET/CT revealed superior diagnostic performance to [18F]Fluorocholine PET/CT in staging and restaging of PC patients, especially in cases with low PSA levels. However, in a few hormone resistant high-risk PC patients, [18F]Fluorocholine PET/CT may improve overall diagnostic accuracy.