Identification of putative enhancer-like elements predicts regulatory networks active in planarian adult stem cells.

Planarians have become an established model system to study regeneration and stem cells, but the regulatory elements in the genome remain almost entirely undescribed. Here, by integrating epigenetic and expression data we use multiple sources of evidence to predict enhancer elements active in the adult stem cell populations that drive regeneration. We have used ChIP-seq data to identify genomic regions with histone modifications consistent with enhancer activity, and ATAC-seq data to identify accessible chromatin. Overlapping these signals allowed for the identification of a set of high-confidence candidate enhancers predicted to be active in planarian adult stem cells. These enhancers are enriched for predicted transcription factor (TF) binding sites for TFs and TF families expressed in planarian adult stem cells. Footprinting analyses provided further evidence that these potential TF binding sites are likely to be occupied in adult stem cells. We integrated these analyses to build testable hypotheses for the regulatory function of TFs in stem cells, both with respect to how pluripotency might be regulated, and to how lineage differentiation programs are controlled. We found that our predicted GRNs were independently supported by existing TF RNAi/RNA-seq datasets, providing further evidence that our work predicts active enhancers that regulate adult stem cells and regenerative mechanisms.

Monitoring Chromatin Regulation in Planarians Using Chromatin Immunoprecipitation Followed by Sequencing (ChIP-seq).

Planarians are an accessible model system to study animal regeneration and stem cells. Over the last two decades, new molecular techniques have provided us with powerful tools to understand whole-body regeneration and pluripotent adult stem cells specifically. We describe a method for performing Chromatin Immunoprecipitation followed by sequencing (ChIP-seq) on planarian cells that relies on FACS to isolate different cell populations followed by immunoprecipitation and library preparation for next-generation sequencing. Whole-genome profiling of histone modifications enables a greater understanding of epigenetic mechanisms in development, pluripotency, and differentiation. This protocol adds to the growing list of functional genomic approaches to study whole-body regeneration in animals.

Demographics of Surgical Specialty Residency Program Directors in the United States: A Cross-sectional Analysis.

OBJECTIVE: To evaluate program director (PD) demographics, training background, and academic productivity in 11 surgical specialties. SUMMARY BACKGROUND DATA: There is currently no comprehensive study comparing educational background, research output, and gender differences between PDs of surgical residencies in the United States. METHODS: The Accreditation Council for Graduate Medical Education (ACGME) and the Association of American Medical Colleges (AAMC) websites were used to identify residency PDs. Age, information related to service as PD, educational background, and research output were collected utilizing online searches including Doximity, PubMed, and Scopus.. The ACGME Data Resource Book was used to obtain data on the gender makeup of residents in each surgical specialty. Data collection occurred between December 14, 2019, and May 9, 2020. RESULTS: 1571 residency PDs across 11 surgical specialties were included. Significant differences between specialties were found with respect to PD gender, current age, age at appointment, years between residency and assignment, term duration, number of PubMed publications, and Scopus h-index. The current age (mean ± SD) ranged from 46.8 ± 8.5 years among Interventional Radiology (IR) PDs to 53.4 ± 9.1 years among Neurological Surgery (NEUROSURG) PDs. The proportion of female PDs ranged from 5.9% in NEUROSURG to 63.5% in Obstetrics and Gynecology (OB-GYN). Completion of a post-residency fellowship was least common for OB-GYN PDs at 9.1%, and most common for IR PDs at 98.8%. The number (mean ± SD) of PubMed publications and Scopus h-index ranged from 13.1 ± 22.3 publications and h index 4.5 ± 5.7 among OB-GYN PDs to 112.5 ± 103.0 publications and h index 27.4 ± 16.7 among Thoracic Surgery PDs. Age and academic productivity as measured by PubMed publications and Scopus h-index were significantly lower among female PDs in multiple surgical specialties. CONCLUSIONS: There were significant variations in the PDs of surgical specialties, particularly with respect to gender and academic productivity. Efforts should be made to support and encourage greater female representation in the role of surgical residency PD.

Ongoing repair of migration-coupled DNA damage allows planarian adult stem cells to reach wound sites.

Mechanical stress during cell migration may be a previously unappreciated source of genome instability, but the extent to which this happens in any animal in vivo remains unknown. We consider an in vivo system where the adult stem cells of planarian flatworms are required to migrate to a distal wound site. We observe a relationship between adult stem cell migration and ongoing DNA damage and repair during tissue regeneration. Migrating planarian stem cells undergo changes in nuclear shape and exhibit increased levels of DNA damage. Increased DNA damage levels reduce once stem cells reach the wound site. Stem cells in which DNA damage is induced prior to wounding take longer to initiate migration and migrating stem cell populations are more sensitive to further DNA damage than stationary stem cells. RNAi-mediated knockdown of DNA repair pathway components blocks normal stem cell migration, confirming that active DNA repair pathways are required to allow successful migration to a distal wound site. Together these findings provide evidence that levels of migration-coupled-DNA-damage are significant in adult stem cells and that ongoing migration requires DNA repair mechanisms. Our findings reveal that migration of normal stem cells in vivo represents an unappreciated source of damage, which could be a significant source of mutations in animals during development or during long-term tissue homeostasis.

Transthoracic Needle Biopsy of Pulmonary Nodules: Meteorological Conditions and the Risk of Pneumothorax and Chest Tube Placement.

The purpose of this paper is to evaluate whether meteorological variables influence rates of pneumothorax and chest tube placement after percutaneous transthoracic needle biopsy (PTNB) of pulmonary nodules. A retrospective review of 338 consecutive PTNBs of pulmonary nodules at a single institution was performed. All procedures implemented a coaxial approach, using a 19-gauge outer guide needle for access and a 20-gauge core biopsy gun with or without a small-gauge aspiration needle for tissue sampling. Correlation between age, sex, smoking history, lesion size, meteorological variables, and frequency of complications were evaluated. Fisher exact, trend and t tests were used to evaluate the relationship between each factor and rates of pneumothorax and chest tube placement. A p value of less than 0.05 was considered to indicate a statistically significant difference. Pneumothorax occurred in 115 of 338 patients (34%). Chest tube placement was required in 30 patients (8.9%). No significant relationship was found between pneumothorax rate and age (p = 0.172), sex (p = 0.909), smoking history (p = 0.819), or lesion location (p = 0.765). The presence or absence of special weather conditions did not correlate with the rate of pneumothorax (p = 0.241) or chest tube placement (p = 0.213). The mean atmospheric temperature (p = 0.619) and degree of humidity (p = 0.858) also did not correlate with differences in the rate of pneumothorax. Finally, mean atmospheric pressure on the day of the procedure demonstrated no correlation with the rate of pneumothorax (p = 0.277) or chest tube placement (p = 0.767). In conclusion, no correlation is demonstrated between the occurrence of pneumothorax after PTNB of pulmonary nodules and the studied meteorological variables.

Planarian flatworms as a new model system for understanding the epigenetic regulation of stem cell pluripotency and differentiation.

Planarian flatworms possess pluripotent stem cells (neoblasts) that are able to differentiate into all cell types that constitute the adult body plan. Consequently, planarians possess remarkable regenerative capabilities. Transcriptomic studies have revealed that gene expression is coordinated to maintain neoblast pluripotency, and ensure correct lineage specification during differentiation. But as yet they have not revealed how this regulation of expression is controlled. In this review, we propose that planarians represent a unique and effective system to study the epigenetic regulation of these processes in an in vivo context. We consolidate evidence suggesting that although DNA methylation is likely present in some flatworm lineages, it does not regulate neoblast function in Schmidtea mediterranea. A number of phenotypic studies have documented the role of histone modification and chromatin remodelling complexes in regulating distinct neoblast processes, and we focus on four important examples of planarian epigenetic regulators: Nucleosome Remodeling Deacetylase (NuRD) complex, Polycomb Repressive Complex (PRC), the SET1/MLL methyltransferases, and the nuclear PIWI/piRNA complex. Given the recent advent of ChIP-seq in planarians, we propose future avenues of research that will identify the genomic targets of these complexes allowing for a clearer picture of how neoblast processes are coordinated at the epigenetic level. These insights into neoblast biology may be directly relevant to mammalian stem cells and disease. The unique biology of planarians will also allow us to investigate how extracellular signals feed into epigenetic regulatory networks to govern concerted neoblast responses during regenerative polarity, tissue patterning, and remodelling.

Updates on MR-Guided Focused Ultrasound for Symptomatic Uterine Fibroids.

Magnetic-resonance-guided focused ultrasound (MRgFUS), also called high-intensity focused ultrasound (HIFU) is an effective, noninvasive uterine-preserving treatment for symptomatic uterine fibroids. As the use of this therapeutic modality is not yet widespread, it may remain unfamiliar to many interventional radiologists. The purpose of this review is to discuss MRgFUS, including technology, patient selection, technique, outcomes, complications, and recent data on fertility and comparative effectiveness.

Post-procedural Care in Interventional Radiology: What Every Interventional Radiologist Should Know-Part II: Catheter Care and Management of Common Systemic Post-procedural Complications.

Interventional radiology (IR) has evolved into a full-fledged clinical specialty with attendant comprehensive patient care responsibilities. Providing excellent and thorough clinical care is as essential to the practice of IR as achieving technical success in procedures. Basic clinical skills that every interventional radiologist should learn include routine management of percutaneously inserted drainage and vascular catheters and rapid effective management of common systemic post-procedural complications. A structured approach to post-procedural care, including routine follow-up and early identification and management of complications, facilitates efficient and thorough management with an emphasis on quality and patient safety. The aim of this second part, in conjunction with part 1, is to complete the comprehensive review of post-procedural care in patients undergoing interventional radiology procedures. We discuss common problems encountered after insertion of drainage and vascular catheters and describe effective methods of troubleshooting these problems. Commonly encountered systemic complications in IR are described, and ways for immediate identification and management of these complications are provided.

Post-procedural Care in Interventional Radiology: What Every Interventional Radiologist Should Know-Part I: Standard Post-procedural Instructions and Follow-Up Care.

Interventional radiology (IR) has evolved into a full-fledged clinical specialty with attendant patient care responsibilities. Success in IR now requires development of a full clinical practice, including consultations, inpatient admitting privileges, and an outpatient clinic. In addition to technical excellence and innovation, maintaining a comprehensive practice is imperative for interventional radiologists to compete successfully for patients and referral bases. A structured approach to periprocedural care, including routine follow-up and early identification and management of complications, facilitates efficient and thorough management with an emphasis on quality and patient safety.

Routine Antibiotic Prophylaxis for Totally Implantable Venous Access Device Placement: Meta-Analysis of 2,154 Patients.

PURPOSE: To provide a meta-analysis of currently available literature on the topic of antibiotic prophylaxis for totally implanted venous access device (TIVAD) placement. MATERIALS AND METHODS: A systematic review of MEDLINE/PubMed was performed to identify studies that met Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria reviewing antibiotic prophylaxis in TIVAD placement. Four studies were identified that met criteria. The analysis included 2,154 patients undergoing TIVAD placement; 360 (16.7%) received antibiotic prophylaxis, and 1,794 (83.3%) received no periprocedural antibiotics. RESULTS: In the period after TIVAD placement, 27 (1.25%) infections were identified. Of infections, five occurred in the antibiotic prophylaxis group (1.39%), and 22 occurred in the nonprophylaxis group (1.23%) with an odds ratio of 0.84 (CI = 0.29-2.35). CONCLUSIONS: The odds ratio of infection was 0.85 with antibiotic use but one was contained within the confidence interval suggesting no significant difference in infection rate when antibiotics were used.

Frequency map for the human cochlear spiral ganglion: implications for cochlear implants.

The goals of this study were to derive a frequency-position function for the human cochlear spiral ganglion (SG) to correlate represented frequency along the organ of Corti (OC) to location along the SG, to determine the range of individual variability, and to calculate an "average" frequency map (based on the trajectories of the dendrites of the SG cells). For both OC and SG frequency maps, a potentially important limitation is that accurate estimates of cochlear place frequency based upon the Greenwood function require knowledge of the total OC or SG length, which cannot be determined in most temporal bone and imaging studies. Therefore, an additional goal of this study was to evaluate a simple metric, basal coil diameter that might be utilized to estimate OC and SG length. Cadaver cochleae (n = 9) were fixed <24 h postmortem, stained with osmium tetroxide, microdissected, decalcified briefly, embedded in epoxy resin, and examined in surface preparations. In digital images, the OC and SG were measured, and the radial nerve fiber trajectories were traced to define a series of frequency-matched coordinates along the two structures. Images of the cochlear turns were reconstructed and measurements of basal turn diameter were made and correlated with OC and SG measurements. The data obtained provide a mathematical function for relating represented frequency along the OC to that of the SG. Results showed that whereas the distance along the OC that corresponds to a critical bandwidth is assumed to be constant throughout the cochlea, estimated critical band distance in the SG varies significantly along the spiral. Additional findings suggest that measurements of basal coil diameter in preoperative images may allow prediction of OC/SG length and estimation of the insertion depth required to reach specific angles of rotation and frequencies. Results also indicate that OC and SG percentage length expressed as a function of rotation angle from the round window is fairly constant across subjects. The implications of these findings for the design and surgical insertion of cochlear implants are discussed.

A frequency-position function for the human cochlear spiral ganglion.

Greenwood's frequency-position function for the organ of Corti (OC) is commonly used to estimate represented frequencies for cochlear implant (CI) electrodes, both in temporal bone studies and in imaging studies of living CI recipients. However, many contemporary CIs position stimulating electrodes near the modiolus, directly targeting the spiral ganglion (SG) cells within Rosenthal's canal. At the extreme base and apex, the SG does not extend as far as the OC, and the radial nerve fibers take a tangential course into the modiolus resulting in a potential offset between the frequency maps of the OC and SG. In this investigation, human cadaveric cochleae (n = 7) were studied in surface preparations after osmium staining. The OC and SG lengths were measured and radial fiber trajectories traced to identify frequency-matched points on each structure. These data allowed derivation of a mathematical function correlating represented frequency along the OC to position along the SG. A cubic function fit the data with a very high intersubject correlation. Better knowledge of the human SG 'neural frequency map' may help to refine electrode design, and to more accurately map CI channel filter bands to the appropriate cochlear place along the SG, which may be advantageous for more sophisticated CI outcomes, such as music appreciation. These data also could be valuable for electroacoustic stimulation, by defining the insertion distance of a CI electrode required to reach specific frequencies (based upon preoperative imaging) in an individual subject, thus helping to avoid trauma to cochlear regions with residual hearing.