Protein signaling and morphological development of the tail fluke in the embryonic beluga whale (Delphinapterus leucas).

BACKGROUND: During the land-to-sea transition of cetaceans (whales, dolphins, and porpoises), the hindlimbs were lost and replaced by an elaborate tail fluke that evolved 32 Ma. All modern cetaceans utilize flukes for lift-based propulsion, and nothing is known of this organ's molecular origins during embryonic development. This study utilizes immunohistochemistry to identify the spatiotemporal location of protein signals known to drive appendage outgrowth in other vertebrates (e.g., Sonic Hedgehog [SHH], GREMLIN [GREM], wingless-type family member 7a [WNT], and fibroblast growth factors [FGFs]) and to test the hypothesis that signals associated with outgrowth and patterning of the tail fluke are similar to a tetrapod limb. Specifically, this study utilizes an embryo of a beluga whale (Delphinapterus leucas) as a case study. RESULTS: Results showed epidermal signals of WNT and FGFs, and mesenchymal/epidermal signals of SHH and GREM. These patterns are most consistent with vertebrate limb development. Overall, these data are most consistent with the hypothesis that outgrowth of tail flukes in cetaceans employs a signaling pattern that suggests genes essential for limb outgrowth and patterning shape this evolutionarily novel appendage. CONCLUSIONS: While these data add insights into the molecular signals potentially driving the evolution and development of tail flukes in cetaceans, further exploration of the molecular drivers of fluke development is required.

Universal DNA methylation age across mammalian tissues.

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.

Key factors for residency interview selection from the National Resident Matching Program: analysis of residency Program Director surveys, 2016-2020.

CONTEXT: As the number of medical school graduates continues to outpace the available residency training positions, applying for residency in the United States has become a highly competitive process, often associated with a low rate of selection and invitation for interview. The National Resident Matching Program (NRMP) Program Director survey provides data assessing factors considered by Program Directors (PD) in selecting and inviting candidates for interview. Assessing the evolution of these factors over time is efficacious to inform and guide prospective applicants toward improving preparation for residency application. OBJECTIVES: We aim to synthesize NRMP data showing factors that PDs reported and rated as important in their decision to select and invite applicants for interview. METHODS: Data from residency PD surveys from 2008 to 2021 were accessed, but after applying inclusion/exclusion criteria, only the data from 2016 to 2020 were reviewed and analyzed. The NRMP survey reports provided two metrics that characterized PDs' evaluation of the residency factors for interview, namely, "percent citing factor" and "average rating" on a 0 to 5 Likert-type scale. These two metrics were combined into an aggregate measure of importance (AI), and another measure of relative importance (RI) was constructed from normalizing the AI of each individual factor to the sum of the AI within each survey year. RESULTS: The top ranked factors were United States Medical Licensing Examination (USMLE) Step 1/Comprehensive Osteopathic Medical Licensing Examination (COMLEX) Level 1, Letter of Recommendation (LOR) in the specialty, Medical Student Performance Evaluation (MSPE/Dean's Letter), and USMLE Step 2 Clinical Knowledge (CK)/COMLEX Level 2 Cognitive Exam (CE) score, any failed attempt in USMLE/COMLEX, and perceived commitment to specialty. Factors rising in importance were Audition Elective/Rotation Within Your Department, Personal Statement (PS), Perceived Commitment to Specialty, Perceived Interest in Program, LOR in the Specialty, Other Life Experience, and Personal Prior Knowledge of the Applicant. Factors with declining importance were Interest in Academic Career, Awards or Special Honors in Basic Sciences, Graduate of Highly Regarded US Medical School, Awards or Special Honors in Clinical Clerkships, Lack of Gaps in Medical Education, Awards or Special Honors in Clerkship in Desired Specialty, and Consistency of Grades. Compared to the 2021 PD survey, our findings show continued predictive consistency, particularly related to specialty and program commitment. CONCLUSIONS: The factors identified for the selection of medical school graduates for interview into a residency program reveal that PDs move toward a more integrated approach. Specifically, PDs are placing increasing emphasis on factors that border on subjective qualities more so than the more traditional, quantitative, and objective metrics. Medical students and educators need to continually apprise themselves of the NRMP data to inform students' preparation endeavors throughout medical school to strengthen their application portfolios and enhance their competitiveness for the matching process.

Tribute to Dianne Rekow-Dental "Imagineer".

Elizabeth Dianne Rekow, BSME, MSME, MBA, DDS, MS, Certificate in Orthodontics, and PhD (1944-2022), was a dental science futurist pursuing brave new paths during her career. She was one of the pivotal scientists who initiated the CAD/CAM movement in the 1980s and went on to focus on digital dentistry for the rest of her career. Her professional contributions involved seven patents, 92 peer-reviewed publications, 10 book contributions, 31 proceeding contributions, and well over 100 national and international presentations. She was an avid supporter of women in science. Her greatest contribution was her expansive imagination. She served as 35th president of the American Association for Dental, Oral, and Craniofacial Research in 2006-2007 and 88th president of the International Association for Dental Research in 2011-2012. The present article reviews key elements of her career and includes testimonies from friends about her special relationships.

Optical feedback control loop for the precise and robust acoustic focusing of cells, micro- and nanoparticles.

Despite a long history and the vast number of applications demonstrated, very few market products incorporate acoustophoresis. Because a human operator must run and control a device during an experiment, most devices are limited to proof of concepts. On top of a possible detuning due to temperature changes, the human operator introduces a bias which reduces the reproducibility, performance and reliability of devices. To mitigate some of these problems, we propose an optical feedback control loop that optimizes the excitation frequency. We investigate the improvements that can be expected when a human operator is replaced for acoustic micro- and nanometer particle focusing experiments. Three experiments previously conducted in our group were taken as a benchmark. In addition to being automatic, this resulted in the feedback control loop displaying a superior performance compared to an experienced scientist in 1) improving the particle focusing by at least a factor of two for 5 µm diameter PS particles, 2) increasing the range of flow rates in which 1 µm diameter PS particles could be focused and 3) was even capable of focusing 600 nm diameter PS particles at a frequency of 1.72075 MHz. Furthermore, the feedback control loop is capable of focusing biological cells in one and two pressure nodes. The requirements for the feedback control loop are: an optical setup, a run-of-the-mill computer and a computer controllable function generator. Thus resulting in a cost-effective, high-throughput and automated method to rapidly increase the efficiency of established systems. The code for the feedback control loop is openly accessible and the authors explicitly wish that the community uses and modifies the feedback control loop to their own needs.

An experimental approach to analyze aerosol and splatter formations due to a dental procedure.

Throughout 2020 and beyond, the entire world has observed a continuous increase in the infectious spread of the novel coronavirus (SARS-CoV-2) otherwise known as COVID-19. The high transmission of this airborne virus has raised countless concerns regarding safety measures employed in the working conditions for medical professionals. Specifically, those who perform treatment procedures on patients which intrinsically create mists of fine airborne droplets, i.e., perfect vectors for this and other viruses to spread. The present study focuses on understanding the splatter produced due to a common dentistry technique to remove plaque buildup on teeth. This technique uses a high-speed dentistry instrument, e.g., a Cavitron ultrasonic scaler, to scrape along the surface of a patient's teeth. This detailed understanding of the velocity and the trajectory of the droplets generated by the splatter will aid in the development of hygiene mechanisms to guarantee the safety of those performing these procedures and people in clinics or hospitals. Optical flow tracking velocimetry (OFTV) method was employed to obtain droplet velocity and trajectory in a two-dimensional plane. Multiple data collection planes were taken in different orientations around a model of adult mandibular teeth. This technique provided pseudo-three-dimensional velocity information for the droplets within the splatter developed from this high-speed dental instrument. These results indicated that within the three-dimensional splatter produced there were high velocities (1-2 m/s) observed directly below the intersection point between the front teeth and the scaler. The splatter formed a cone-shape structure that propagated 10-15 mm away from the location of the scaler tip. From the droplet trajectories, it was observed that high velocity isolated droplets propagate away from the bulk of the splatter. It is these droplets which are concerning for health safety to those performing the medical procedures. Using a shadowgraphy technique, we further characterize the individual droplets' size and their individual velocity. We then compare these results to previously published distributions. The obtained data can be used as a first step to further examine flow and transport of droplets in clinics/dental offices.

Effect of H2O2 Antiseptic on Dispersal of Cavitation-Induced Microdroplets.

The persisting outbreak of SARS-CoV-2 has posed an enormous threat to global health. The sustained human-to-human transmission of SARS-CoV-2 via respiratory droplets makes the medical procedures around the perioral area vulnerable to the spread of the disease. Such procedures include the ultrasonic dental cleaning method, which occurs within the oral cavity and involves cavitation-induced sprays, thus increasing the risk of pathogen transmission via advection. To understand the associated health and safety risks for patients and clinicians, it is critical to understand the flow pattern of the spray cloud around the operating region, the size and velocity distribution of the emitted droplets, and the extent of fluid dispersion until ultimate deposit on surfaces or escape through air vents. In this work, the droplet size and velocity distributions of the spray emerging from the tip of a free-standing common ultrasonic dental cleaning device were characterized via high-speed imaging. Deionized water and 1.5% and 3% aqueous hydrogen peroxide (H2O2) solutions were used as working fluids, with the H2O2-an established oxidizing agent-intended to curb the survival of virus released in aerosols generated from dental procedures. The measurements reveal that the presence of H2O2 in the working fluid increases the mean droplet size and ejection velocity. Detailed computational fluid dynamic simulations with multiphase flow models reveal benefits of adding small amounts of H2O2 in the feed stream of the ultrasonic cleaner; this practice causes larger droplets with shorter residence times inside the clinic before settling down or escaping through air vents. The results suggest optimal benefits (in terms of fluid spread) of adding 1.5% H2O2 in the feed stream during dental procedures involving ultrasonic tools. The present findings are not specific to the COVID-19 pandemic but should also apply to future outbreaks caused by airborne droplet transmission.

Safety of emergency, elective and day case operating during the winter period at East Suffolk and North Essex NHS Foundation Trust: lessons from the outcomes of 4,254 surgical patients from the first COVID-19 wave.

BACKGROUND: There is limited evidence on perioperative outcomes of surgical patients during the COVID-19 pandemic to inform continued operating into the winter period. METHODS: We retrospectively analysed the rate of 30-day COVID-19 transmission and mortality of all surgical patients in the three hospitals in our trust in the East of England during the first lockdown in March 2020. All patients who underwent a swab were swabbed on or 24 hours prior to admission. RESULTS: There were 4,254 patients and an overall 30-day mortality of 0.99%. The excess surgical mortality in our region was 0.29%. There were 39 patients who were COVID-19 positive within 30 days of admission, 12 of whom died. All 12 were emergency admissions with a length of stay longer than 24 hours. There were three deaths among those who underwent day case surgery, one of whom was COVID-19 negative, and the other two were not swabbed but not suspected to have COVID-19. There were two COVID-19 positive elective cases and none in day case elective or emergency surgery. There were no COVID-19 positive deaths in elective or day case surgery. CONCLUSIONS: There was a low rate of COVID-19 transmission and mortality in elective and day case operations. Our data have allowed us to guide patients in the consent process and provided the evidence base to restart elective and day case operating with precautions and regular review. A number of regions will be similarly affected and should perform a review of their data for the winter period and beyond.

Reflecting on success in trauma research: experiences from the SGCNS and SIR studies.

The inclusion of British Service Personnel (SP) lacking capacity into research studies from the point of injury through to medium-term rehabilitation had not previously been undertaken until work to support operations in Afghanistan (2001-2014). The Surgeon General's Casualty Nutrition Study and the Steroids and Immunity from Injury through to Rehabilitation Study sought to address the nutrition, endocrine and immune responses in a military patient cohort. A fundamental part of research is to feedback to patients, their relatives and ward staff on data collection and outcomes, and how future research may be improved to better support both injured SP and trauma patients in the UK. This paper will provide an experiential view on the delivery, operations and infrastructure requirements that should be considered when developing military research at a role-3 facility, before, during and after a study.

A Prospective Pilot Study to Identify a Myocarditis Cohort who may Safely Resume Sports Activities 3 Months after Diagnosis.

International cardiovascular society recommendations to return to sports activities following acute myocarditis are based on expert consensus in the absence of prospective studies. We prospectively enrolled 30 patients with newly diagnosed myocarditis based on clinical parameters, laboratory measurements and cardiac magnetic resonance imaging with mildly reduced or preserved left ventricular ejection fraction (LVEF) with a follow-up of 12 months. Cessation of physical activity was recommended for 3 months. The average age was 35 (19-80) years with 73% male patients. One case of non-sustained ventricular tachycardia was recorded during 48-h-Holter electrocardiogram. Except for this case, all patients were allowed to resume physical exercise after 3 months. At 6- (n = 26) and 12-month (n = 19) follow-up neither cardiac events nor worsening LVEF were recorded. The risk of cardiac events at 1 year after diagnosis of myocarditis appears to be low after resumption of exercise after 3 months among patients who recover from acute myocarditis.

A unity of opposites: A prototypical case for the importance of primary-care providers in addressing mental health issues.

Primary-care providers are most often the first point of contact for patients presenting with mental illness. Highly stigmatized and with a litany of other medical issues requiring redress by providers, it may receive inadequate attention, despite its unintuitive consequences. Therefore, the purpose of this case is to demonstrate the potential catastrophic consequences of untreated mental illness by providers. As a result of a serious suicide attempt by a patient afflicted with bipolar disorder, this patient presented with significant blood loss secondary to multiple self-inflicted lacerations to the wrist, parasternal stab wounds, and a resultant hemopneumothorax. By juxtaposing this patient's mental illness with his other traditionally "more" concerning medical history (i.e., multiple myeloma, Factor V Leiden, and recurrent DVTs), we are forced to reexamine where mental illness resides in the hierarchy of treatment.

Meningococcal carriage by age in the African meningitis belt: a systematic review and meta-analysis.

Meningococcal carriage dynamics drive patterns of invasive disease. The distribution of carriage by age has been well described in Europe, but not in the African meningitis belt, a region characterised by frequent epidemics of meningitis. We aimed to estimate the age-specific prevalence of meningococcal carriage by season in the African meningitis belt. We searched PubMed, Web of Science, the Cochrane Library and grey literature for papers reporting carriage of Neisseria meningitidis in defined age groups in the African meningitis belt. We used a mixed-effects logistic regression to model meningococcal carriage prevalence as a function of age, adjusting for season, location and year. Carriage prevalence increased from low prevalence in infants (0.595% in the rainy season, 95% CI 0.482-0.852%) to a broad peak at age 10 (1.94%, 95% CI 1.87-2.47%), then decreased in adolescence. The odds of carriage were significantly increased during the dry season (OR 1.5 95% CI 1.4-1.7) and during outbreaks (OR 6.7 95% CI 1.6-29). Meningococcal carriage in the African meningitis belt peaks at a younger age compared to Europe. This is consistent with contact studies in Africa, which show that children 10-14 years have the highest frequency of contacts. Targeting older children in Africa for conjugate vaccination may be effective in reducing meningococcal transmission.

Experimental platform to facilitate novel back brace development for the improvement of spine stability.

The spine or 'back' has many functions including supporting our body frame whilst facilitating movement, protecting the spinal cord and nerves and acting as a shock absorber. In certain instances, individuals may develop conditions that not only cause back pain but also may require additional support for the spine. Common movements such as twisting, standing and bending motions could exacerbate these conditions and intensify this pain. Back braces can be used in certain instances to constrain such motion as part of an individual's therapy and have existed as both medical and retail products for a number of decades. Arguably, back brace designs have lacked the innovation expected in this time. Existing designs are often found to be heavy, overly rigid, indiscrete and largely uncomfortable. In order to facilitate the development of new designs of back braces capable of being optimised to constrain particular motions for specific therapies, a numerical and experimental design strategy has been devised, tested and proven for the first time. The strategy makes use of an experimental test rig in conjunction with finite element analysis simulations to investigate and quantify the effects of back braces on flexion, extension, lateral bending and torsional motions as experienced by the human trunk. This paper describes this strategy and demonstrates its effectiveness through the proposal and comparison of two novel back brace designs.

Use of antibacterial toothpaste is associated with higher urinary triclosan concentrations in Asian immigrant women living in Vancouver, Canada.

BACKGROUND: Triclosan is an antibacterial added to consumer products including toothpastes, cosmetics, and plastic cutting boards. Known to disrupt reproductive and hormonal functioning in animals, epidemiological studies indicate that exposure to triclosan may have similar effects on human health. METHODS: 100 women aged 19 to 45 years born in India or China, Hong Kong, and Taiwan new to the Vancouver (Canada) area were recruited in 2015-2016 by word of mouth, public advertisements, and contacts in health and cultural organizations. Participants completed an interview which queried potential sources of triclosan exposure at home and at work and their urine was tested for triclosan by GC-MS. Determinants of urinary triclosan were assessed by Wilcoxon signed-rank test. RESULTS: Triclosan was detected in 62% of urine samples, with an overall GM of 14.5 µg/L (95% CI: 9.7-21.7 µg/L; range:

C5L2 Regulates DMP1 Expression during Odontoblastic Differentiation.

The presence of stem cells within the dental-pulp tissue as well as their differentiation into a new generation of functional odontoblast-like cells constitutes an important step of the dentin-pulp regeneration. Recent investigations demonstrated that the complement system activation participates in 2 critical steps of dentin-pulp regeneration: pulp progenitor's recruitment and pulp nerve sprouting. Surprisingly, its implication in odontoblastic differentiation has not been addressed yet. Since the complement receptor C5a receptor-like 2 (C5L2) is expressed by different stem cells, the aim of this study is to investigate if the dental pulp stem cells express C5L2 and if this receptor participates in odontoblastic differentiation. Immunohistochemistry performed on human third molar pulp sections showed a perivascular co-localization of the mesenchymal stem cell markers STRO1 and C5L2. In vitro immunofluorescent staining confirmed that hDPSCs express C5L2. Furthermore, we determined by real-time polymerase chain reaction that the expression of C5L2 is highly modulated in human dental pulp stem cells (hDPSCs) undergoing odontoblastic differentiation. Moreover, we showed that this odontogenesis-regulated expression of C5L2 is specifically potentiated by the proinflammatory cytokine TNFα. Using a C5L2-siRNA silencing strategy, we provide direct evidence that C5L2 constitutes a negative regulator of the dentinogenic marker DMP1 (dentin matrix protein 1) expression by hDPSCs. Our findings suggest a direct correlation between the odontoblastic differentiation and the level of C5L2 expression in hDPSCs and identify C5L2 as a negative regulator of DMP1 expression by hDPSCs during the odontoblastic differentiation and inflammation processes. This work is the first to demonstrate the involvement of C5L2 in the biological function of stem cells, provides an important knowledge in understanding odontoblastic differentiation of dental pulp stem cells, and may be useful in future dentin-pulp engineering strategies.