Caffeine induces alveolar bone loss in rats submitted to orthodontic movement via activation of receptor activator of nuclear factor Ò¡B, receptor activator of nuclear factor Ò¡B ligand, and osteoprotegerin pathway.

INTRODUCTION: Caffeine is a widely consumed substance with several effects on bone metabolism. This study aimed to investigate the effect of caffeine on the bone tissue of rats submitted to orthodontic movement. METHODS: Twenty-five male Wistar rats underwent orthodontic movement (21 days) of the first permanent maxillary molars on the left side. The experimental group (caffeine; n = 13) and control group (n = 12) received caffeine and water, respectively, by gavage. Microcomputed tomography was performed to analyze orthodontic movement. Histologic analysis of the inflammatory infiltrate and osteoclast count by tartrate-resistant acid phosphatase were conducted. Maxilla tissue was evaluated for receptor activator of nuclear factor Ò¡B (RANK), RANK ligand (RANKL), and osteoprotegerin by immunohistochemistry. RESULTS: Caffeine exhibited a lower bone volume/tissue volume ratio (78.09% ± 5.83%) than the control (86.84% ± 4.89%; P <0.05). Inflammatory infiltrate was increased in the caffeine group compared with the control group (P <0.05). A higher number of tartrate-resistant acid phosphatase-positive cells was observed in the caffeine (9.67 ± 1.73) than in the control group (2.66 ± 0.76; P <0.01). Immunoexpression of RANK and RANKL in the caffeine group was greater than the control (P <0.05). CONCLUSIONS: The use of caffeine thermogenic induces alveolar bone loss in rats submitted to orthodontic movement via activation of RANK, RANKL, and osteoprotegerin signaling pathways.

Design and Rationale for the Direct Oral Anticoagulant Apixaban in Left Ventricular Assist Devices (DOAC LVAD) Study.

Implantable left ventricular assist device (LVAD) therapy is used to improve quality of life, alleviate symptoms and extend survival rates in patients with advanced heart failure. Patients with LVADs require chronic anticoagulation to reduce the risk of thromboembolic complications, and they commonly experience bleeding events. Apixaban is a direct oral anticoagulant that has become first-line therapy for patients with nonvalvular atrial fibrillation and venous thromboembolism; however, its safety in patients with LVADs has not been well characterized. The evaluation of the hemocompatibility in the DOAC LVAD (Direct Oral Anti-Coagulant apixaban in Left Ventricular Assist Devices) trial is a phase 2, open-label trial of patients with LVADs who were randomized to either apixaban or warfarin therapy. Patients randomized to apixaban will be started on a dosage of 5 mg twice daily, whereas those randomized to warfarin will be managed at an International Normalized Ratio goal of 2.0-2.5. All patients will be treated with aspirin at 81 mg daily. We plan to randomize and follow as many as 40 patients for 24 weeks to evaluate the primary outcomes of freedom from death or hemocompatibility-related adverse events (stroke, device thrombosis, bleeding, aortic root thrombus, and arterial non-CNS thromboembolism). The DOAC LVAD trial will establish the feasibility of apixaban anticoagulant therapy in patients with LVADs. Clinicaltrials.gov: NCT04865978.

Cardiovascular disease, surgery and outcomes in women: are they any different.

PURPOSE OF REVIEW: Cardiovascular disease is a leading cause of death for women worldwide and continues to be a major determinant of significant morbidity. Several studies have investigated the marked differences in diagnosis, treatment and etiology in cardiovascular disease and how it relates to gender. In this review, several key studies highlight the stark differences and bring light to the disparity and potential opportunities for further research. RECENT FINDINGS: One noted area of gender disparity is ischemic cardiac disease as it relates to surgical management. Women have historically had delays in diagnosis, inferior surgical revascularization techniques, and inadequate postoperative care when compared to men. SUMMARY: By highlighting the disparities in cardiovascular ischemic care, the hope is to bring attention and future research to a population group that is currently undertreated for their ischemic disease and suffering high mortality rates.

Percutaneous approach to left ventricular assist device decommissioning.

OBJECTIVE: To assess the outcomes of a single-center experience with percutaneous left ventricular assist device (LVAD) decommissioning. BACKGROUND: Patients with LVADs may eventually require their removal, either due to recovery of left ventricular function or recurrent complications. Traditionally, withdrawal of LVAD support has been managed with surgical device explantation, which carries significant procedural risks. Transcatheter LVAD decommissioning, with outflow graft occlusion and driveline transection, has recently been described as an alternative to surgical removal. METHODS: Here, we report on a retrospective cohort of five consecutive cases treated with transcatheter LVAD decommissioning. RESULTS: The procedure was effective in all cases, and no patient experienced procedure-related complications. At midterm follow-up, the three patients who had myocardial function recovery were alive and had not experienced heart failure-related symptoms or complications. CONCLUSION: Percutaneous LVAD decommissioning appears to be a safe and effective approach to LVAD treatment discontinuation.

Association of a longitudinal, preclinical ultrasound curriculum with medical student performance.

INTRODUCTION: Point-of-care ultrasound (US) is used in clinical practice across many specialties. Ultrasound (US) curricula for medical students are increasingly common. Optimal timing, structure, and effect of ultrasound education during medical school remains poorly understood. This study aims to retrospectively determine the association between participation in a preclinical, longitudinal US curriculum and medical student academic performance. METHODS: All first-year medical students at a medical school in the Midwest region of the United States were offered a voluntary longitudinal US curriculum. Participants were selected by random lottery. The curriculum consisted of five three-hour hands on-sessions with matching asynchronous content covering anatomy and pathologic findings. Content was paired with organ system blocks in the standard first year curriculum at our medical school. Exam scores between the participating and non-participating students were compared to evaluate the objective impact of US education on performance in an existing curriculum. We hypothesized that there would be an association between participation in the curriculum and improved medical student performance. Secondary outcomes included shelf exam scores for the surgery, internal medicine, neurology clerkships and USMLE Step 1. A multivariable linear regression model was used to evaluate the association of US curriculum participation with student performance. Scores were adjusted for age, gender, MCAT percentile, and science or engineering degree. RESULTS: 76 of 178 students applied to participate in the curriculum, of which 51 were accepted. US curriculum students were compared to non-participating students (n = 127) from the same class. The US curriculum students performed better in cardiovascular anatomy (mean score 92.1 vs. 88.7, p = 0.048 after adjustment for multiple comparisons). There were no significant differences in cumulative cardiovascular exam scores, or in anatomy and cumulative exam scores for the gastroenterology and neurology blocks. The effect of US curriculum participation on cardiovascular anatomy scores was estimated to be an improvement of 3.48 points (95% CI 0.78-6.18). No significant differences were observed for USMLE Step 1 or clerkship shelf exams. There were no significant differences in either preclinical, clerkship or Step 1 score for the 25 students who applied and were not accepted and the 102 who did not apply. CONCLUSIONS: Participation in a preclinical longitudinal US curriculum was associated with improved exam performance in cardiovascular anatomy but not examination of other cardiovascular system concepts. Neither anatomy or comprehensive exam scores for neurology and gastrointestinal organ system blocks were improved.

Dronabinol inhibits alveolar bone remodeling in tooth movement of rats.

INTRODUCTION: Orthodontic tooth movement is reliant on the process of bone remodeling, and a variety of medications impact the ability of teeth to move through bone. Marijuana is the most widely used recreational drug in the world, and early studies suggest the drug impacts bone remodeling as tetrahydrocannabinol binds to cannabinoid receptors which play a role in bone homeostasis. This study aimed to assess the impact of dronabinol on alveolar bone remodeling in rats with otherwise healthy tissue when subjected to orthodontic forces. METHODS: Thirty male Sprague Dawley rats were equally allocated into 2 groups. Orthodontic appliances were placed in all animals, which consisted of a nickel-titanium coil ligated from the maxillary first molar to the central incisor. The appliance was activated to deliver a force to move teeth together. Over 21 days, daily injections of either dronabinol or the control (solvent) were given to the rats. Cephalometric analysis, histology, and bone remodeling profiles of both groups were analyzed and compared. RESULTS: Teeth moved in both the dronabinol and control groups (P <0.05). Tooth movement in the control group followed the typical process of orthodontic tooth movement: periodontal width narrowing and bone resorption on the compression side of the tooth, with an overall decrease in the height of the alveolar bone. In contrast, the dronabinol group showed an abnormal response to tooth movement: no bone resorption on the compression side of the tooth, increased bone formation on the tension side, and the maintenance of the height of the alveolar crest. In the dronabinol group, there were also significantly more osteoclasts and osteoblasts in the alveolar bone than in the control group. CONCLUSIONS: These results demonstrate that dronabinol attenuates orthodontic tooth movement by decreasing bone resorption, which could have implications for other bone-related recovery processes.

Post-legalization Consumption of Cannabis at Massachusetts General Hospital Dental Group.

AIM: The aim of this study was to evaluate the profile of patients undergoing dental treatment in relation to cannabis use. MATERIALS AND METHODS: A comprehensive questionnaire was used to address the type of cannabis preparations, route of intake, frequency of usage, and potential reasoning for use (recreational vs medical use) of patients from the MGH Dental Group. RESULTS: Seventy-six adult patients completed the survey. Sixty-one percent of the participants were female, with the majority (59%) of the participants being ≥51 years or older. Twelve of the 76 participants (16%) were 18-30 years old. The remaining 19 patients (25%) who participated in the study were 31-50 years old. The sample included participants who were predominately non-Hispanic (63 patients, 83%) and White (59 patients, 78%). The majority of patients either had their first use of cannabis prior to 18 years of age (36%) or did not respond to this question (34%) at all. The predominant age at consistent cannabis use was 18-30 years (13%). The most common method of cannabis intake in the preceding year for participants was smoking, followed by ingesting, using cannabidiol (CBD), and vaping (least common). Recreational cannabis use was reported in 47% of the participants vs 28% of participants who reported cannabis intake for medical use. CONCLUSION: This preliminary study characterized the profile of patients undergoing dental treatment in relation to marijuana use. Diminishing restraints to cannabis use may affect the dental profession. CLINICAL SIGNIFICANCE: It is important for dentists to understand cannabis-related oral health conditions to provide customized patient treatments.

Molecular Evaluation of Fluoroquinolone Resistance in Serial Mycobacterium tuberculosis Isolates from Individuals Diagnosed with Multidrug-Resistant Tuberculosis.

Fluoroquinolones (FQ) are crucial components of multidrug-resistant tuberculosis (MDR TB) treatment. Differing levels of resistance are associated with specific mutations within the quinolone-resistance-determining region (QRDR) of gyrA We sequenced the QRDR from serial isolates of MDR TB patients in the Preserving Effective TB Treatment Study (PETTS) with baseline FQ resistance (FQR) or acquired FQ resistance (FQACQR) using an Ion Torrent Personal Genome Machine (PGM) to a depth of 10,000× and reported single nucleotide polymorphisms in ≥1% of reads. FQR isolates harbored 15 distinct alleles with 1.3 (maximum = 6) on average per isolate. Eighteen alleles were identified in FQACQR isolates with an average of 1.6 (maximum = 9) per isolate. Isolates from 78% of FQACQR individuals had mutant alleles identified within 6 months of treatment initiation. Asp94Gly was the predominant allele in the initial FQ-resistant isolates followed by Ala90Val. Seventy-seven percent (36/47) of FQACQR group patients had isolates with FQ resistance alleles prior to changes to the FQ component of their treatment. Unlike the individuals treated initially with other FQs, none of the 21 individuals treated initially with levofloxacin developed genotypic or phenotypic FQ resistance, although country of residence was likely a contributing factor since 69% of these individuals were from a single country. Initial detection of phenotypic resistance and genotypic resistance occurred simultaneously for most; however, phenotypic resistance occurred earlier in isolates harboring mixtures of alleles of very low abundance (<1% of reads), whereas genotypic resistance often occurred earlier for alleles associated with low-level resistance. Understanding factors influencing acquisition and evolution of FQ resistance could reveal strategies for improved treatment success.

HMGB2 is associated with pressure loading in chondrocytes of temporomandibular joint: In vitro and in vivo study.

High mobility group protein B2 (HMGB2) is an important protein attributed to tissue function and homeostasis in osteoarthritis (OA), however, its roles in the temporomandibular joint with mechanical pressure are unclear. This study investigated the expression patterns of HMGB2 in chondrocytes of TMJ on OA-related cellular and animal models. The transcriptional level and protein expression of HMGB2 as well as Col- II, MMP-13 and ß-catenin were examined in primary cultured chondrocytes from TMJs with hydrostatic pressures (HP). The immunohistochemistry of HMGB2, Col- II, MMP13 and ß-catenin in rabbits with surgical anterior disc displacement (ADD) were analyzed. The results indicated that HP decreased the mRNA expression of HMGB2, MMP-13, and ß-catenin. HMGB2 knockdown attenuated the sensitivity of chondrocytes response to pressure loading. Immunohistochemical results showed that the rabbits with ADD exhibited thinner condylar cartilage with disordered cell arrangement. The distribution of HMGB2 was chiefly in the fibrous layer and the proliferative layer of the condylar cartilage. In rabbit cartilage with ADD, the expression of HMGB2 and ß-catenin were elevated at 1 week followed by sustained decrease at 2 and 4 weeks. Our findings suggested that HMGB2 is necessary for TMJ chondrocytes to sense pressure loading, which plays an important role in the pathogenesis of chondrogenesis and TMJOA following mechanical loading.

Initial Public Health Laboratory Response After Hurricane Maria - Puerto Rico, 2017.

Hurricane Maria made landfall in Puerto Rico on September 20, 2017, causing major damage to infrastructure and severely limiting access to potable water, electric power, transportation, and communications. Public services that were affected included operations of the Puerto Rico Department of Health (PRDOH), which provides critical laboratory testing and surveillance for diseases and other health hazards. PRDOH requested assistance from CDC for the restoration of laboratory infrastructure, surveillance capacity, and diagnostic testing for selected priority diseases, including influenza, rabies, leptospirosis, salmonellosis, and tuberculosis. PRDOH, CDC, and the Association of Public Health Laboratories (APHL) collaborated to conduct rapid needs assessments and, with assistance from the CDC Foundation, implement a temporary transport system for shipping samples from Puerto Rico to the continental United States for surveillance and diagnostic and confirmatory testing. This report describes the initial laboratory emergency response and engagement efforts among federal, state, and nongovernmental partners to reestablish public health laboratory services severely affected by Hurricane Maria. The implementation of a sample transport system allowed Puerto Rico to reinitiate priority infectious disease surveillance and laboratory testing for patient and public health interventions, while awaiting the rebuilding and reinstatement of PRDOH laboratory services.

A Women in Radiology Group Fosters Career Development for Faculty and Trainees.

OBJECTIVE: The objective of our study was to evaluate the outcomes of a women in radiology (WIR) group during the first 6 years of its existence, including members' satisfaction, activities, and differences based on seniority. MATERIALS AND METHODS: An anonymous questionnaire was distributed to group members. Survey questions were related to the usefulness of sessions, mentoring, professional opportunities, and camaraderie. Comparisons were made on the basis of training status and seniority. Continuous variables were compared using means, t tests, and correlations, and categoric variables were compared using counts, percentages, and chi-square tests or Mantel-Haenszel tests. RESULTS: Surveys were sent to 61 women, including trainees and faculty; the response rate was 49% (38% of trainees and 53% of faculty). Overall satisfaction score for WIR sessions was high (mean summary score, 1.42 ± 0.37 [SD], with 1 meaning very satisfied and 4 meaning very unsatisfied). Trainees and junior faculty were more likely than senior faculty to report expanded internal networking opportunities (94% vs 69%; p = 0.07), to have gained a mentor (67% vs 8%; p = 0.001), and to have increased research involvement (33% vs 0%; p = 0.02). Both groups were equally likely to have become mentors. Almost all respondents (93%) reported increased camaraderie among women in the department. CONCLUSION: A WIR group can provide career development tools for its members. In this study, trainees and junior faculty reported increased networking and research involvement and gaining a mentor but were equally likely as senior faculty to have become mentors. Most members reported increased camaraderie among women in the department. A WIR group may help to accelerate professional development among trainees and junior faculty, thereby contributing to a more diverse and enabled workforce.

Breast care problems on call: training residents to manage effectively.

PURPOSE: Our aim was to assess and address the challenges radiology residents face when managing breast imaging emergencies on call and to determine if targeted educational interventions improved resident confidence and knowledge. METHODS: We created surveys to determine resident comfort level with and knowledge of appropriate management of breast imaging emergencies. We also created structured educational interventions to improve resident confidence and knowledge. The effectiveness of these interventions was assessed with pre- and post-intervention surveys given to the 43 residents at our institution. RESULTS: Thirty-six of the 43 residents at our institution completed both surveys. The results showed that 33 of 36 residents (91.7%) felt an increase in their comfort level after utilizing one or both of the interventions. There was also significant improvement in resident knowledge; the average resident score on the knowledge questions improved from 40 to 68% (p < 0.0001). CONCLUSION: Managing breast imaging emergencies on call can be challenging and stressful for residents. Educational interventions such as our targeted teaching tools can significantly improve resident confidence and knowledge. Presenting dedicated teaching materials directed at a previously identified knowledge deficit and source of stress significantly improved resident knowledge base and confidence in managing breast imaging emergencies on call.

Applied clinical anatomy: the successful integration of anatomy into specialty-specific senior electives.

PURPOSE: A strong foundation in anatomical knowledge is essential for physicians in all fields. Despite this established importance, anatomy continues to be primarily taught only during the pre-clinical years of medical school. Senior medical students have more mature clinical reasoning and analytical skills; therefore, advanced anatomy courses have great potential to integrate basic and clinical sciences to better prepare senior medical students for residency. METHODS: At our institution, five electives have been implemented that integrate anatomical education in clinical contexts in the fields of emergency medicine, musculoskeletal medicine, radiology, surgery, and obstetrics and gynecology. These 4-week courses are all offered in the spring of the final year of medical school. The course curricula, content, and evaluation data are described for each of the courses. RESULTS: The five electives have been extremely popular at our institution, and all have been consistently filled each year by students entering diverse disciplines. Course evaluations have been positive and students specifically note how these courses allow them the opportunity to integrate basic anatomical knowledge into clinical contexts. Students have marked improvement in anatomical knowledge after completion of these electives. CONCLUSIONS: Advanced anatomy courses that integrate anatomical education with clinical reasoning are important curricular innovations that are popular with students and lead to important improvements in anatomical knowledge. Anatomists can lead the charge for better integration of basic sciences into senior medical school curricula.

Breast imaging after dark: patient outcomes following evaluation for breast abscess in the emergency department after hours.

In our study, we sought to report the management, clinical outcomes, and follow-up rates of patients who presented for evaluation of breast abscess in the Emergency Department (ED) after hours. A retrospective search of ultrasound reports at our institution identified all patients from January 1, 2009 to June 30, 2013 who were scanned in the ED after hours to evaluate for breast abscess. Patient demographics, clinical information, imaging findings, follow-up rates, and outcomes were reviewed. One hundred eighty-five patients were included in the study. Forty-four percent (86/185) of the patients were diagnosed with abscess based on ultrasound findings in the ED. Twenty-seven percent (23/86) were recently post-operative, and 12 % (10/86) were postpartum/breastfeeding. Mastitis was the diagnosis in the remaining 54 % (99/185). Only 1/86 cases were associated with breast cancer. Seventy-seven percent (66/86) of patients were treated with an invasive procedure; 39 % (26/66) had surgical evacuation, 30 % (20/66) image-guided drainage, 23 % (15/66) bedside or clinic incision and drainage, and 8 % (5/66) palpation-guided fine needle aspiration (FNA). Seventy-seven percent (143/185) of patients had clinical and/or imaging follow-up. Forty-four percent (63/143) had long-term follow-up (≥ 3 months). Almost 50 % of the patients who presented to the ED for evaluation of abscess were diagnosed with abscess while the remaining patients were diagnosed with mastitis. Appropriate clinical and/or imaging follow-up occurred in 77 %. Long-term follow-up (≥ 3 months) occurred more frequently in patients older than 30 years of age. Appropriate follow-up does not occur in approximately one fourth of cases, suggesting that additional clinician and patient education is warranted.

Outcomes of solid palpable masses assessed as BI-RADS 3 or 4A: a retrospective review.

The purpose of this study was to evaluate the outcomes and cancer rate in solid palpable masses with benign features assessed as BI-RADS 3 or 4A. This study was Institutional Review Board approved. Mammography and breast ultrasound reports in our Radiology Information System were searched for solid, palpable masses with benign features described from 1/1/2000 to 12/31/2009, and retrospectively reviewed. Those masses prospectively assessed as BI-RADS 3 or 4A, or suggestive of a fibroadenoma or other benign pathology were retrieved. Chart review was used to assess outcomes and cancer rate. Basic summary measures were summarized and compared between BI-RADS 3 and 4A groups using Wilcoxon Rank Sum test for continuous data or Fisher's exact test for categorical data. The cancer rate across age quartiles was assessed using Cochran-Armitage trend test. 573 solid palpable masses with benign features in 487 women were identified. There were 197 BI-RADS 3 and 376 BI-RADS 4A masses. The overall cancer rate was 1.6 % (9/573). All cancers were BI-RADS 4A (cancer rate 2.4 %-9/376). Smaller mean size and younger age at presentation in BI-RADS 3 women was found compared to BI-RADS 4A (P < 0.0001). There was a significant increase in cancer rate across age quartiles (P = 0.03124). The cancer rate is very low in solid palpable masses with benign features. In particular, BI-RADS 3 palpable masses in young women may undergo close surveillance without immediate biopsy, confirming what other investigators have found. All cancers were in the BI-RADS 4A group with increasing incidence with age, with over half occurring in women over 40 years old. Palpable masses in women 40 and older with benign features should be considered for immediate biopsy.

The Habsburg Jaw-re-examined.

"Habsburg Jaw" is a frequently used eponymous designation for patients with mandibular prognathism, hyperplasia, or overgrowth. The purpose of this study was to evaluate portraits of the Spanish Habsburgs to determine the relative contributions of maxillary deficiency and mandibular prognathism to overall facial appearance. Representative portraits of the Spanish Habsburgs were assessed by 4 investigators for the presence of 11 anatomic features of maxillary deficiency and 7 of mandibular prognathism. Each characteristic was given a binary score of 1 if present and 0 if absent. Thus, the maximum score would be 11 for maxillary deficiency and 7 for mandibular prognathism. A semi-quantitative scale was established to determine the likelihood of each diagnosis: Maxillary deficiency: 0-4.99 (unlikely), 5-7.99 (likely), 8-11 (very likely); mandibular prognathism: 0-2.99 (unlikely), 3-5.99 (likely), 6-7 (very likely). Six of 7 Habsburg rulers were considered either likely or very likely to have maxillary deficiency, whereas 3/7 were assessed as likely and 4 unlikely to have mandibular prognathism. The results of this study suggest that the primary deformity of the "Habsburg Jaw" is maxillary deficiency rather than absolute mandibular prognathism.

Retrospective research in radiology from concept to publication: a stepwise guide for trainees and mentors.

OBJECTIVE: The purpose of this article is to describe a step-by-step approach to the successful mentorship of trainees completing retrospective radiology research projects. The topics addressed include selection of a mentor and mentee and the selection, planning, initiation, and completion of a retrospective research project. CONCLUSION: Mentoring a trainee in the completion of a retrospective research project is an ideal way to introduce a trainee to academics. The goals of such a project given the time constraints of radiology residents include completion of an educational exhibit, an oral scientific presentation, and a published manuscript.

Imaging of breast cancer-related changes after surgical therapy.

OBJECTIVE: The purpose of this article is to discuss the surgical treatment of breast cancer and its resultant thoracic CT and multimodality imaging manifestations. CONCLUSION: Many breast cancer patients undergo cross-sectional imaging at some point during or after treatment. Thoracic CT is an important modality performed for staging and surveillance. Thoracic CT examinations often show findings related to patients' surgical or adjuvant treatment. The postsurgical changes visible on thoracic CT may include those related to lumpectomy, mastectomy, breast reconstruction, and axillary surgery. Postsurgical complications may also be seen, including fluid collections, infection, fat necrosis, and lymphedema. Recognition and appropriate interpretation of the posttherapeutic spectrum of findings are important to avoid unnecessary diagnostic imaging and minimize patient anxiety.