Opportunities for Cancer Prevention During Midlife Highlights from a Meeting of Experts

AbstractThis paper provides highlights from a CDC-hosted meeting on opportunities for cancer prevention during midlife (roughly ages 45–64 years). Positive changes during this phase of life have the potential to prevent cancer incidence later in life, making this phase an opportune time for targeted prevention efforts to facilitate healthy aging and increased longevity. Risk and protective factors discussed during the meeting included exposure to radiation from medical imaging procedures, circadian disruption, chemical exposures, dietary factors, alcohol consumption, obesity, physical activity, diabetes, and the human microbiome. Although many of these factors are well recognized as being related to cancer incidence, others are not as widely recognized or have emerged as growing areas of research.Meeting participants discussed promising strategies for cancer prevention targeting this age group. Just as there are multiple determinants of cancer risk, there are likely multiple solutions. Changes to social and physical environments may facilitate healthy behaviors and minimize harmful exposures. Information shared during the meeting about health disparities in the U.S. highlighted the need to go beyond traditional approaches to cancer prevention to truly reach vulnerable populations. Partnerships are also a key component to prevention efforts; community-based and nonprofit organizations, the healthcare system, research institutions, state health departments, and federal agencies were all noted as important partners in prevention efforts. Coordinated, multi-disciplinary efforts across multiple chronic diseases may provide opportunities for synergistic effects. Further, leveraging key partnerships and existing communication channels can maximize success and facilitate timely translation of research findings into public health practice

Criteria for the diagnosis of corticobasal degeneration

Current criteria for the clinical diagnosis of pathologically confirmed corticobasal degeneration (CBD) no longer reflect the expanding understanding of this disease and its clinicopathologic correlations. An international consortium of behavioral neurology, neuropsychology, and movement disorders specialists developed new criteria based on consensus and a systematic literature review. Clinical diagnoses (early or late) were identified for 267 nonoverlapping pathologically confirmed CBD cases from published reports and brain banks. Combined with consensus, 4 CBD phenotypes emerged: corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS). Clinical features of CBD cases were extracted from descriptions of 209 brain bank and published patients, providing a comprehensive description of CBD and correcting common misconceptions. Clinical CBD phenotypes and features were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies. Probable CBD criteria require insidious onset and gradual progression for at least 1 year, age at onset ≥50 years, no similar family history or known tau mutations, and a clinical phenotype of probable CBS or either FBS or naPPA with at least 1 CBS feature. The possible CBD category uses similar criteria but has no restrictions on age or family history, allows tau mutations, permits less rigorous phenotype fulfillment, and includes a PSPS phenotype. Future validation and refinement of the proposed criteria are needed

Screening for Gynecologic Conditions With Pelvic Examination US Preventive Services Task Force Recommendation Statement

IMPORTANCE Many conditions that can affect women\u27s health are often evaluated through pelvic examination. Although the pelvic examination is a common part of the physical examination, it is unclear whether performing screening pelvic examinations in asymptomatic women has a significant effect on disease morbidity and mortality. OBJECTIVE To issue a new US Preventive Services Task Force(USPSTF) recommendation on screening for gynecologic conditions with pelvic examination for conditions other than cervical cancer, gonorrhea, and chlamydia, for which the USPSTF has already made specific recommendations. EVIDENCE REVIEW The USPSTF reviewed the evidence on the accuracy, benefits, and potential harms of performing screening pelvic examinations in asymptomatic, nonpregnant adult women 18 years and older who are not at increased risk for any specific gynecologic condition. FINDINGS Overall, the USPSTF found inadequate evidence on screening pelvic examinations for the early detection and treatment of a range of gynecologic conditions in asymptomatic, nonpregnant adult women. CONCLUSIONS AND RECOMMENDATION The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of performing screening pelvic examinations in asymptomatic, nonpregnant adult women. (I statement) This statement does not apply to specific disorders for which the USPSTF already recommends screening (ie, screening for cervical cancer with a Papanicolaou smear, screening for gonorrhea and chlamydia)

Surgical Explantation of Transcatheter Aortic Valve Bioprostheses: A Statewide Experience

BACKGROUND: Despite the rapid adoption of transcatheter aortic valve replacement (TAVR) since its initial approval in 2011, the frequency and outcomes of surgical explantation of TAVR devices (TAVR-explant) is poorly understood. METHODS: Patients undergoing TAVR-explant between January 2012 and June 2020 at 33 hospitals in Michigan were identified in the Society of Thoracic Surgeons Database and linked to index TAVR data from the Transcatheter Valve Therapy Registry through a statewide quality collaborative. The primary outcome was operative mortality. Indications for TAVR-explant, contraindications to redo TAVR, operative data, and outcomes were collected from Society of Thoracic Surgeons and Transcatheter Valve Therapy databases. Baseline Society of Thoracic Surgeons Predicted Risk of Mortality was compared between index TAVR and TAVR-explant. RESULTS: Twenty-four surgeons at 12 hospitals performed TAVR-explants in 46 patients (median age, 73). The frequency of TAVR-explant was 0.4%, and the number of explants increased annually. Median time to TAVR-explant was 139 days and among known device types explanted, most were self-expanding valves (29/41, 71%). Common indications for TAVR-explant were procedure-related failure (35%), paravalvular leak (28%), and need for other cardiac surgery (26%). Contraindications to redo TAVR included need for other cardiac surgery (28%), unsuitable noncoronary anatomy (13%), coronary obstruction (11%), and endocarditis (11%). Overall, 65% (30/46) of patients underwent concomitant procedures, including aortic repair/replacement in 33% (n=15), mitral surgery in 22% (n=10), and coronary artery bypass grafting in 16% (n=7). The median Society of Thoracic Surgeons Predicted Risk of Mortality was 4.2% at index TAVR and 9.3% at TAVR-explant (P=0.001). Operative mortality was 20% (9/46) and 76% (35/46) of patients had in-hospital complications. Of patients alive at discharge, 37% (17/37) were discharged home and overall 3-month survival was 73±14%. CONCLUSIONS: TAVR-explant is rare but increasing, and its clinical impact is substantial. As the utilization of TAVR expands into younger and lower-risk patients, providers should consider the potential for future TAVR-explant during selection of an initial valve strategy

A Cis-Regulatory Map of the Drosophila Genome

Systematic annotation of gene regulatory elements is a major challenge in genome science. Direct mapping of chromatin modification marks and transcriptional factor binding sites genome-wide1, 2 has successfully identified specific subtypes of regulatory elements3. In Drosophila several pioneering studies have provided genome-wide identification of Polycomb response elements4, chromatin states5, transcription factor binding sites6, 7, 8, 9, RNA polymerase II regulation8 and insulator elements10; however, comprehensive annotation of the regulatory genome remains a significant challenge. Here we describe results from the modENCODE cis-regulatory annotation project. We produced a map of the Drosophila melanogaster regulatory genome on the basis of more than 300 chromatin immunoprecipitation data sets for eight chromatin features, five histone deacetylases and thirty-eight site-specific transcription factors at different stages of development. Using these data we inferred more than 20,000 candidate regulatory elements and validated a subset of predictions for promoters, enhancers and insulators in vivo. We identified also nearly 2,000 genomic regions of dense transcription factor binding associated with chromatin activity and accessibility. We discovered hundreds of new transcription factor co-binding relationships and defined a transcription factor network with over 800 potential regulatory relationships

LATE-NC staging in routine neuropathologic diagnosis : an update

An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases with unusual features that do not fit with current diagnostic categories. The goal of this report is to update the neuropathologic criteria for the diagnosis and staging of LATE-NC, based primarily on published data. We provide practical suggestions about how to integrate available genetic information and comorbid pathologies [e.g., Alzheimer's disease neuropathologic changes (ADNC) and Lewy body disease]. We also describe recent research findings that have enabled more precise guidance on how to differentiate LATE-NC from other subtypes of TDP-43 pathology [e.g., frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)], and how to render diagnoses in unusual situations in which TDP-43 pathology does not follow the staging scheme proposed in 2019. Specific recommendations are also made on when not to apply this diagnostic term based on current knowledge. Neuroanatomical regions of interest in LATE-NC are described in detail and the implications for TDP-43 immunohistochemical results are specified more precisely. We also highlight questions that remain unresolved and areas needing additional study. In summary, the current work lays out a number of recommendations to improve the precision of LATE-NC staging based on published reports and diagnostic experience.Peer reviewe

Shelled pteropods in peril: Assessing vulnerability in a high CO2 ocean

The impact of anthropogenic ocean acidification (OA) on marine ecosystems is a vital concern facing marine scientists and managers of ocean resources. Euthecosomatous pteropods (holoplanktonic gastropods) represent an excellent sentinel for indicating exposure to anthropogenic OA because of the sensitivity of their aragonite shells to the OA conditions less favorable for calcification. However, an integration of observations, experiments and modelling efforts is needed to make accurate predictions of how these organisms will respond to future changes to their environment. Our understanding of the underlying organismal biology and life history is far from complete and must be improved if we are to comprehend fully the responses of these organisms to the multitude of stressors in their environment beyond OA. This review considers the present state of research and understanding of euthecosomatous pteropod biology and ecology of these organisms and considers promising new laboratory methods, advances in instrumentation (such as molecular, trace elements, stable isotopes, palaeobiology alongside autonomous sampling platforms, CT scanning and high-quality video recording) and novel field-based approaches (i.e. studies of upwelling and CO2 vent regions) that may allow us to improve our predictive capacity of their vulnerability and/or resilience. In addition to playing a critical ecological and biogeochemical role, pteropods can offer a significant value as an early-indicator of anthropogenic OA. This role as a sentinel species should be developed further to consolidate their potential use within marine environmental management policy making