Farm animal exposure, respiratory illnesses, and nasal cell gene expression.

BACKGROUND: Farm exposures in early life reduce the risks for childhood allergic diseases and asthma. There is less information about how farm exposures relate to respiratory illnesses and mucosal immune development. OBJECTIVE: We hypothesized that children raised in farm environments have a lower incidence of respiratory illnesses over the first 2 years of life than nonfarm children. We also analyzed whether farm exposures or respiratory illnesses were related to patterns of nasal cell gene expression. METHODS: The Wisconsin Infant Study Cohort included farm (n = 156) and nonfarm (n = 155) families with children followed to age 2 years. Parents reported prenatal farm and other environmental exposures. Illness frequency and severity were assessed using illness diaries and periodic surveys. Nasopharyngeal cell gene expression in a subset of 64 children at age 2 years was compared to farm exposure and respiratory illness history. RESULTS: Farm versus nonfarm children had nominally lower rates of respiratory illnesses (rate ratio 0.82 [95% CI, 0.69, 0.97]) with a stepwise reduction in illness rates in children exposed to 0, 1, or ≥2 animal species, but these trends were nonsignificant in a multivariable model. Farm exposures and preceding respiratory illnesses were positively related to nasal cell gene signatures for mononuclear cells and innate and antimicrobial responses. CONCLUSIONS: Maternal and infant exposure to farms and farm animals was associated with nonsignificant trends for reduced respiratory illnesses. Nasal cell gene expression in a subset of children suggests that farm exposures and respiratory illnesses in early life are associated with distinct patterns of mucosal immune expression.

Student challenges during third-year perioperative clerkships through the lens of faculty and residents: A qualitative study.

PURPOSE: Studies of medical students suggest they often find the transition from the pre-clinical curriculum to clinical rotations particularly challenging during perioperative clerkships. Educators could add a new perspective into students' clerkship experiences and potential interventions to improve them. The purpose of this study was to examine the educator perspective on students' experiences in perioperative clerkships. The findings could inform potential curricular interventions to facilitate student transition from a didactic environment into perioperative clerkships. METHODS: Semi-structured qualitative interviews were conducted with 16 faculty and residents in the departments of anaesthesia, obstetrics and gynaecology (OBGYN), and general surgery across multiple clinical teaching sites at one institution. Interview questions explored their perceptions of the challenges students face during their transition into perioperative clerkships and probed thoughts on curriculum interventions they believed would be the most beneficial. Interviews were recorded, transcribed and analysed thematically. FINDINGS: Three themes were identified. Faculty and residents perceive that student experiences on perioperative clerkships are shaped by (1) students' ability to adapt to the specialty and operating room norms on these clerkships, (2) students' understanding of how they can meaningfully contribute to the clinical team, and (3) dedicated teaching time constraints. Interventions were suggested to address educator expectations and student gaps, such as implementing a pre-clerkship orientation across anaesthesia, general surgery and OBGYN. CONCLUSIONS: To facilitate the medical student transition to perioperative clerkships, interventions should aid students in adapting to clerkship norms for these specialties and clarifying their role and expectations within the care team.

Inadequate Lymph Node Yield: An Inadequate Indication for Adjuvant Chemotherapy in Stage II Colon Cancer.

Background: Optimal therapy for stage II colon cancer remains unclear, and national guidelines recommend "consideration" of adjuvant chemotherapy (ACT) in the presence of high-risk features, including inadequate lymph node yield (LNY, <12 nodes). This study aims to determine whether the survival benefit of ACT in stage II disease varies based on the adequacy of LNY. Methods: We used the National Cancer Database (NCDB) to identify adults who underwent resection for a single primary T3 or T4 colon cancer between 2006 and 2018. Multivariable logistic regression tested for associations between ACT and prespecified demographic and clinical characteristics, including the adequacy of LNY. We used Cox proportional hazards models to assess overall survival and restricted cubic splines to estimate the optimal LNY threshold to dichotomize patients based on overall survival. Results: Unadjusted 5- and 10-year survival rates were 84% and 75%, respectively, among patients who received ACT and 70% and 50% among patients who did not (log-rank P < 0.01). Inadequate LNY was independently associated with both receipt of ACT (odds ratios, 1.50; P < 0.01) and decreased overall survival [hazard ratio (HR), 1.56; P < 0.01]. ACT was independently associated with improved survival (HR, 0.67; P < 0.01); this effect size did not change based on the adequacy of LNY (interaction P = 0.41). Results were robust to re-analysis with our cohort-optimized threshold of 18 lymph nodes. Conclusions: Consistent with contemporary guidelines, patients with inadequate LNY are more likely to receive ACT. LNY adequacy is an independent prognostic factor but, in isolation, should not dictate whether patients receive ACT.

Human nucleolar protein 7 (NOL7) is required for early pre-rRNA accumulation and pre-18S rRNA processing.

The main components of the essential cellular process of eukaryotic ribosome biogenesis are highly conserved from yeast to humans. Among these, the U3 Associated Proteins (UTPs) are a small subunit processome subcomplex that coordinate the first two steps of ribosome biogenesis in transcription and pre-18S processing. While we have identified the human counterparts of most of the yeast Utps, the homologs of yeast Utp9 and Bud21 (Utp16) have remained elusive. In this study, we find that NOL7 is the likely ortholog of Bud21. Previously described as a tumour suppressor through regulation of antiangiogenic transcripts, we now show that NOL7 is required for early pre-rRNA accumulation and pre-18S rRNA processing in human cells. These roles lead to decreased protein synthesis and induction of the nucleolar stress response upon NOL7 depletion. Beyond Bud21's nonessential role in yeast, we establish human NOL7 as an essential UTP that is necessary to maintain both early pre-rRNA levels and processing.

Exploring the complexity and spectrum of racial/ethnic disparities in colon cancer management.

BACKGROUND: Colorectal cancer is a leading cause of morbidity and mortality across U.S. racial/ethnic groups. Existing studies often focus on a particular race/ethnicity or single domain within the care continuum. Granular exploration of disparities among different racial/ethnic groups across the entire colon cancer care continuum is needed. We aimed to characterize differences in colon cancer outcomes by race/ethnicity across each stage of the care continuum. METHODS: We used the 2010-2017 National Cancer Database to examine differences in outcomes by race/ethnicity across six domains: clinical stage at presentation; timing of surgery; access to minimally invasive surgery; post-operative outcomes; utilization of chemotherapy; and cumulative incidence of death. Analysis was via multivariable logistic or median regression, with select demographics, hospital factors, and treatment details as covariates. RESULTS: 326,003 patients (49.6% female, 24.0% non-White, including 12.7% Black, 6.1% Hispanic/Spanish, 1.3% East Asian, 0.9% Southeast Asian, 0.4% South Asian, 0.3% AIAE, and 0.2% NHOPI) met inclusion criteria. Relative to non-Hispanic White patients: Southeast Asian (OR 1.39, p < 0.01), Hispanic/Spanish (OR 1.11 p < 0.01), and Black (OR 1.09, p < 0.01) patients had increased odds of presenting with advanced clinical stage. Southeast Asian (OR 1.37, p < 0.01), East Asian (OR 1.27, p = 0.05), Hispanic/Spanish (OR 1.05 p = 0.02), and Black (OR 1.05, p < 0.01) patients had increased odds of advanced pathologic stage. Black patients had increased odds of experiencing a surgical delay (OR 1.33, p < 0.01); receiving non-robotic surgery (OR 1.12, p < 0.01); having post-surgical complications (OR 1.29, p < 0.01); initiating chemotherapy more than 90 days post-surgery (OR 1.24, p < 0.01); and omitting chemotherapy altogether (OR 1.12, p = 0.05). Black patients had significantly higher cumulative incidence of death at every pathologic stage relative to non-Hispanic White patients when adjusting for non-modifiable patient factors (p < 0.05, all stages), but these differences were no longer statistically significant when also adjusting for modifiable factors such as insurance status and income. CONCLUSIONS: Non-White patients disproportionately experience advanced stage at presentation. Disparities for Black patients are seen across the entire colon cancer care continuum. Targeted interventions may be appropriate for some groups; however, major system-level transformation is needed to address disparities experienced by Black patients.

Understanding and identifying the needs of parent caregivers of children with hydrocephalus: a qualitative study.

OBJECTIVE: Hydrocephalus is inherently unpredictable. Most parents whose child is diagnosed with hydrocephalus do not anticipate the diagnosis, nor can anyone predict if or when a child's shunt will fail and require emergency surgery. Previous research has shown that children with hydrocephalus and their caregivers experience significant posttraumatic stress symptoms secondary to the diagnosis. This study aims to understand caregiver experiences and needs, identify gaps in resources/support, and determine opportunities to improve care. METHODS: Semistructured interviews were conducted with parent caregivers of children with hydrocephalus to learn about their experiences with the hydrocephalus diagnosis, hospitalizations, surgeries, coping and support, challenges of caring for a child with hydrocephalus, and logistics for a proposed support program. De-identified interviews were audio-recorded, transcribed, and analyzed for themes. RESULTS: Thematic saturation was reached after 17 interviews. Five major themes emerged: 1) coping with the diagnosis, 2) received support, 3) hydrocephalus management, 4) implications for intervention, and 5) psychosocial stressors for caregivers. A top priority was balanced, trustworthy information delivered with compassion and updated throughout the child's life. Caregivers described a variety of coping strategies, but a majority reported a need for support in processing complex emotions and dealing with the uncertainty of their child's hydrocephalus. Most agreed that having a caregiver support network, medical professionals available for referrals and questions, and referrals to support services and therapies would facilitate feeling supported and providing the best care for their children. CONCLUSIONS: Parent caregivers are critical to the health and well-being of children with hydrocephalus, and it is essential to understand their experiences to improve care. Providing well-defined information, psychosocial support, and resources will help to equip parent caregivers to be advocates for their children and to improve both the caregiver and the child's quality of life.

Treatment and post-operative follow-up of pulmonary sclerosing pneumocytoma: A case report.

Introduction and importance: Pulmonary sclerosing pneumocytoma (PSP) is a rare tumor thought to originate from respiratory epithelial cells. It is usually benign, but may rarely metastasize to lymph nodes. Surgeons face unique challenges in diagnosis and management of this condition, and ideal surgical management is yet to be established. Case presentation: 48-year-old woman with a 7 × 7 mm pulmonary lesion discovered incidentally on computerized tomography (CT) imaging, which grew to 9 mm over the following year. Seven years later, follow-up imaging revealed that the mass had grown to 1.3 cm in largest dimension. Surgery was recommended and the mass was resected via a right video-assisted thoracic surgery (VATS) middle lobectomy with mediastinal lymph node dissection. All lymph nodes were negative and the patient's postoperative course was unremarkable. Clinical discussion: There are few evidence-based guidelines available on the treatment and postoperative surveillance of PSP. Research has shown comparable recurrence-free survival rates for sublobar resection and lobectomy, though recurrence can occur, especially following sublobar resection in larger or more centrally-located tumors. In absence of established guidelines, it was decided to follow this patient according to NCCN guidelines for surveillance of early-stage non-small cell lung cancer due to potential risk of recurrence. Conclusion: This case report adds to the limited literature on PSP and depicts a possible treatment and postoperative follow-up plan. Right VATS middle lobectomy can effectively treat some cases of central PSP. In absence of established guidelines for postoperative follow-up of PSP, NCCN guidelines may outline one possible strategy for postoperative management.

Outcomes of Anastomotic Evaluation Using Indocyanine Green Fluorescence during Minimally Invasive Esophagectomy.

BACKGROUND: Limited evidence exists assessing whether anastomotic evaluation using indocyanine green fluorescence (IGF) during minimally invasive esophagectomy (MIE) predicts or improves outcomes. We hypothesized that IGF helps surgeons predict anastomotic complications and reduces anastomotic leaks after MIE. METHODS: In September 2019, our institution began routinely using IGF for intraoperative evaluation of anastomoses during MIE. Data were collected from patients undergoing MIE in the two years before and after this technology began being routinely used. Baseline characteristics and outcomes, including anastomotic leak, in patients who underwent indocyanine green fluorescence evaluation (ICG) and those who did not (nICG) were compared. Outcomes were also compared between ICG patients with normal versus abnormal fluorescence. RESULTS: Overall, 181 patients were included. Baseline demographic and clinical characteristics did not differ between the ICG and nICG groups. ICG patients experienced higher rates of anastomotic leak (10.2% vs. 1.6%, P = .015) and 90-day mortality (8.5% vs. 1.6%, P = .04) compared to nICG patients. Due to lack of equipment availability, 19 nICG patients underwent MIE after the use of IGF became routine, and none developed leaks. ICG patients with abnormal fluorescence had higher rates of anastomotic leak (71.4% vs 1.9%, P < .001) and 30-day mortality (28.6% vs 0%, P = .012) compared to those with normal fluorescence. DISCUSSION: Abnormal intraoperative IGF was associated with increased rate of anastomotic leak, suggesting predictive potential of IGF. However, its use was associated with an increased leak rate and higher mortality. Further studies are warranted to assess possible physiologic effects of indocyanine green on the esophageal anastomosis.

Video-assisted thoracoscopic surgery (VATS) enucleation of large gastroesophageal junction leiomyoma: A case report.

INTRODUCTION AND IMPORTANCE: Esophageal leiomyomas are the most common benign esophageal tumors. They are typically smaller than 3 cm, but larger tumors can impede local structures to cause symptoms, including dysphagia and epigastric pain. Surgical treatment of esophageal leiomyomas has historically involved open thoracotomy, but this approach is being replaced by minimally invasive approaches, including video-assisted thoracoscopic surgery (VATS). CASE PRESENTATION: A 46-year-old female patient presented with upper abdominal pain. Computerized tomography (CT) scanning of the abdomen and chest revealed a large (6.0 × 4.0 × 3.0 cm) gastroesophageal junction (GEJ) mass. An endoscopic ultrasound (EUS) with fine needle aspiration confirmed diagnosis of esophageal leiomyoma. A right VATS esophageal mass resection was performed to enucleate the mass. An intraoperative EGD was performed to check mucosal integrity, ensure adequate lumen patency, and visualization and insufflation was negative for a mucosal leak. The post-operative course was unremarkable. CLINICAL DISCUSSION: This case report adds to the emerging evidence that VATS can be utilized for enucleation of larger leiomyomas (>5 cm in largest dimension). Additionally, the use of direct intraoperative endoscopic evaluation via esophagoscopy suggests that larger esophageal masses could potentially be enucleated with a combined VATS and endoscopic approach. CONCLUSION: The purpose of this report is to add to the limited literature on minimally invasive surgical treatment of a relatively large GEJ leiomyoma. This case highlights that VATS, in addition to simultaneous endoscopic visualization, is an efficacious and safe option for treatment of larger leiomyomas (>5 cm) and can be associated with minimal risk.

The effect of a smoke-evacuation unit on ultrafine particle concentrations in the operating room during approach to the proximal tibia for tibial plateau-leveling osteotomy surgery in dogs.

OBJECTIVE: To evaluate the effectiveness of a smoke-evacuation unit on reducing ultrafine particle concentration in the operating room (OR) during the approach to the proximal tibia for tibial plateau-leveling osteotomy (TPLO). STUDY DESIGN: Prospective, randomized, controlled clinical trial. SAMPLE POPULATION: Twenty-nine client-owned dogs undergoing unilateral TPLO at a single institution were assigned to either smoke-evacuator groups (SE; n = 15) or non-smoke-evacuator groups (NSE; n = 14). METHODS: Dogs were randomly assigned to the SE group or the NSE group. An airborne particle measuring device measured and recorded baseline and intraoperative particles per cm3 (ppc) during the approach to the proximal tibia during which electrosurgery was used to provide hemostasis, dissect subcutis, transect and elevate fascia. The mean ppc, maximum ppc, and baseline ppc were compared between groups. Mean ppc was also compared to the baseline ppc within each group. RESULTS: During surgery, mean ppc (1352) and maximum ppc (62 450) for the NSE group were higher in than mean ppc (763) and maximum ppc (10 100) for the SE group (P < .0001, P < .0001, respectively). Mean ppc was higher in both SE (mean ppc = 763; P < .0001) and NSE (mean ppc = 1352; P = .0001) than their respective baseline ppc (213 and 240). CONCLUSION: The use of a smoke evacuator decreased particle concentrations 56.4% during the approach to the proximal tibia. Performing the approach to the proximal tibia resulted in higher particle concentrations than the baseline, regardless of smoke-evacuator use. CLINICAL SIGNIFICANCE: Surgeons should be aware of smoke produced by electrosurgery, potential health consequences, and methods of smoke mitigation (smoke evacuation).

Determination of anatomic level of myelomeningocele by prenatal ultrasound.

PURPOSE: Ultrasound is the primary method for prenatal identification of myelomeningocele and is critical to prognostication and treatment planning. No study has considered the degree of inaccuracy of prenatal US lesion level estimates and anatomic lesion level on postnatal imaging using the weighted kappa coefficient (κw), nor the impact of maternal BMI on agreement. We examined the accuracy of prenatal ultrasound lesion level estimation in a cohort of patients with myelomeningocele using κw and determined whether BMI influenced accuracy. METHODS: The study is a retrospective review including patients born 2011-2019 who had prenatal imaging and primary myelomeningocele closure at a single institution. Lesion levels from prenatal ultrasound and postnatal imaging studies were analyzed for agreement at exact level, within 1 level, and within 2 levels using κw. Maternal BMI was examined for correlation with accuracy. RESULTS: Fifty-seven patients met inclusion criteria. Mean BMI was 31.2. There was no association between maternal BMI and agreement at any level. Lesion level on prenatal ultrasound agreed with postnatal imaging to the exact level in 13 (22.8%) cases, within 1 level in 38 (66.7%) cases, and within 2 levels in 50 (87.7%) cases. Weighted kappa showed moderate agreement at exact level (κw = 0.494) and substantial agreement within 1 (κw = 0.761) and 2 levels (κw = 0.902). CONCLUSION: Weighted kappa adds confidence for clinical decision making by accounting for accuracy. Prenatal ultrasound is a reliable and accurate method of determining lesion level with near-perfect agreement to postnatal imaging within 2 spinal levels. Maternal BMI may not influence lesion level determination after initial diagnosis.

Greater trochanter morphology and association with patient demographics, surgical factors, and post-operative stem position: a retrospective assessment of 150 cementless THRs in 135 dogs.

BACKGROUND: Total hip replacement (THR) in the gold standard surgical treatment for the canine hip. While it has been shown that greater trochanter morphology affects post-operative cementless stem position in humans, trochanter morphology and the effect on cementless stem position has not been extensively evaluated in dogs. The objective of this study was to classify greater trochanter morphology and identify potential associations between trochanter morphology and patient demographics, femoral canal geometry, surgical time, technique modifications, and post-operative stem position in client-owned dogs undergoing cementless THR. RESULTS: In this retrospective study, medical records and radiographs of 135 dogs undergoing 150 cementless total hip replacements from 2013 to 2020 were included. Trochanters were classified in the frontal plane using an ordinal grading system adapted from human THR. A Grade I trochanter denoted a trochanter positioned lateral to the periosteal surface of the lateral femoral cortex, whereas a Grade IV trochanter denoted a trochanter positioned medial to the anatomic axis of the femur. Associations between trochanter grade and other variables were examined using ANOVA, Kruskall-Wallis, or chi-squared tests. Significance was assumed at P ≤ .05. Trochanters were classified as follows: Grade I (44/150, 29.3%), Grade II (56/150, 37.4%), Grade III (44/150, 29.3%), Grade IV (6/150, 4.0%). Grade IV trochanters had lower anatomic lateral distal femoral angle (aLDFA; 91.0 ± 6.2°), angle of inclination (117.7 ± 10.5°), and canal flare index (1.53 ± 0.27). When compared to all groups, Grade IV trochanters were associated with longer surgical times (Grade IV: 227.0 ± 34.2 min; all grades: 183.2 ± 32.9 min) and technique modifications (Grade IV: 83.3%; all grades: 18%). Grade I trochanters had stems placed in valgus (- 1.8 ± 2.33°), whereas Grade II (0.52 ± 2.36°), III (0.77 ± 2.58°), and IV (0.67 ± 2.73°) trochanters exhibited varus stems. Depth of stem insertion was greater (11.2 ± 4.2 mm) for Grade IV trochanters. CONCLUSIONS: Trochanter grade was associated with post-operative stem alignment and translation in the frontal plane. Grade IV trochanters were associated with altered femoral geometry, increased surgical time, technique modifications, and stem insertion depth. Pre-operative greater trochanter classification may prove useful in identifying cases requiring prolonged surgical times or technique modifications.

Building skill-sets, confidence, and interest for diverse scientific careers in the biological and biomedical sciences.

Many biological science PhD graduates are increasingly pursuing careers outside of academia. Subsequently, PhD training programs are increasing their efforts to broaden their awareness of diverse career opportunities, with a firm knowledge of the skills necessary for success. At Yale University, for two semesters we have offered a new course for graduate students in the biological sciences titled "Skills Development for Diverse Scientific Careers" (BBS 550b). This course addressed career-related topics not covered in any curriculum at Yale such as how to run clinical trials, the business side of biotech, how to convert CVs into resumes, and resilience for early career scientists. We sought to better equip students to think broadly about their career options by exposing them to non-academic biomedical career avenues. Furthermore, the course fulfilled a gap in current curricular offerings to prepare students for multiple science career trajectories. Results on a pre-post course survey demonstrated increases in students' interest for, knowledge of, and confidence in securing a position in multiple nontraditional career sectors. Intentional course design can provide an adequate foundation to broaden awareness of myriad career options available to bioscientists. Broadening student knowledge and interest levels will contribute substantially to developing a robust scientific workforce.

Post-Traumatic Stress Symptoms in Caregivers and Children with Hydrocephalus.

OBJECTIVE: Hydrocephalus is a disorder of cerebrospinal fluid dynamics, traditionally treated by placement of a ventricular shunt. Shunts are effective but imperfect as they fail in an unpredictable pattern, and the patient's well-being is dependent on adequate shunt function. The omnipresent threat of shunt failure along with the potential need for invasive investigations can be stressful for patients and caregivers. Our objective was to measure post-traumatic stress symptoms (PTSS) in children with hydrocephalus and their caregivers. METHODS: A cross-sectional analysis of children with hydrocephalus and their caregivers was conducted. Caregivers completed a measure of their own PTSS (the Post-Traumatic Stress Disorders Checklist for the Diagnostic and Statistical Manual of Mental Disorders-V) and resilience (the Connor Davidson Resilience Scale). Pediatric patients rated their own PTSS and resilience using the Acute Stress Checklist for Kids and Connor Davidson Resilience Scale. RESULTS: Ninety-one caregivers completed the Post-Traumatic Stress Disorders Checklist for the Diagnostic and Statistical Manual of Mental Disorders-V. Mean score was 17.0 (standard deviation 15.7; median 13.0). Fourteen percent scored above 33, the threshold suggestive of a preliminary diagnosis of post-traumatic stress disorder. There was a statistically significant association between caregiver post-traumatic stress and marital status, child's race, and caregiver education. More than half (52%) of caregivers reported their child's hydrocephalus as the most significant source of their PTSS. Children did not have markedly elevated levels of PTSS. Forty-one percent of caregivers and 60% of children scored in the lowest resilience quartile compared with the general population. CONCLUSIONS: Results from this study suggest that post-traumatic stress affects caregivers with hydrocephalus, yet levels of resilience for caregivers and pediatric patients are low.

Responsibilities and capabilities of health engagement professionals (HEPs): Perspectives from HEPs and health consumers in Australia.

BACKGROUND: In Australia, the National Safety and Quality Health Service Standards (2012) stipulates that partnering with health consumers to improve health-care experiences is one of the criteria health-care organizations are assessed and accredited against. This standard has given rise to a role: health engagement professionals (HEPs). While there are no standard requirements for recruitment into this role, this study contributes to much needed research into understanding their responsibilities and capabilities, and their contributions to engagement outcomes. METHODS: Using a qualitative, interpretive approach, 16 HEPs and 15 health consumer representatives (who have experiences of interacting with HEPs) participated in an in-depth phone interview in December 2019. We explored (a) the purposes of the role, (b) the responsibilities and work activities and (c) the capabilities required to carry out the responsibilities. RESULTS: Health engagement professionals are specialists in designing engagement mechanisms for health-care organizations to co-design health services with health consumers. They facilitate partnerships between health-care organizations and health consumers. They play significant roles in listening to, facilitating understanding amongst different stakeholder groups (eg hospital management, health-care workers and health consumers) and navigating the bureaucratic structures to influence outcomes. Four major responsibilities (advocacy, education, facilitation and administration) and four categories of capabilities (relational, communication, professional and personal) were identified. CONCLUSION: A list of job responsibilities and desired capabilities of HEPs is provided to help health-care organizations better understand the requirements for the role. This would help them decide how applicants to these roles would meet the requirements (eg experience of navigating bureaucratic systems).

Paired Box 9 (PAX9), the RNA polymerase II transcription factor, regulates human ribosome biogenesis and craniofacial development.

Dysregulation of ribosome production can lead to a number of developmental disorders called ribosomopathies. Despite the ubiquitous requirement for these cellular machines used in protein synthesis, ribosomopathies manifest in a tissue-specific manner, with many affecting the development of the face. Here we reveal yet another connection between craniofacial development and making ribosomes through the protein Paired Box 9 (PAX9). PAX9 functions as an RNA Polymerase II transcription factor to regulate the expression of proteins required for craniofacial and tooth development in humans. We now expand this function of PAX9 by demonstrating that PAX9 acts outside of the cell nucleolus to regulate the levels of proteins critical for building the small subunit of the ribosome. This function of PAX9 is conserved to the organism Xenopus tropicalis, an established model for human ribosomopathies. Depletion of pax9 leads to craniofacial defects due to abnormalities in neural crest development, a result consistent with that found for depletion of other ribosome biogenesis factors. This work highlights an unexpected layer of how the making of ribosomes is regulated in human cells and during embryonic development.

Effect of sedation or general anesthesia on elbow goniometry and thoracic limb circumference measurements in dogs with naturally occurring elbow osteoarthritis.

OBJECTIVE: To evaluate the effect of sedation or general anesthesia (GA) on elbow goniometry and thoracic limb circumference (TLC) measurements in dogs with elbow osteoarthritis (OA). STUDY DESIGN: Prospective study. ANIMALS: Twenty-four client-owned dogs with radiographically confirmed elbow OA. METHODS: Elbow goniometry and TLC measurements were made before and after either sedation or GA by using a hand-held goniometer and spring tension measuring tape, respectively. Observers were not allowed to review their pre-sedation or pre-GA measurements at the time of obtaining measurements on dogs under sedation or GA. Mixed analysis of variance models were used to compare elbow goniometry and TLC measurements before and after sedation or GA. RESULTS: Eleven and thirteen dogs were included in the sedation and GA groups, respectively. Mean elbow flexion decreased by 5° and 3° and mean elbow extension increased by 6° and 2° under sedation and GA, respectively. Total range of motion increased by 11° under sedation and by 5° under GA. Each of these changes was statistically significant (P < .05) except elbow extension under GA (P = .129). Sedation and GA did not influence TLC measurements (P > .05). CONCLUSION: Sedation or GA led to slight and similar increase in elbow flexion and extension but did not influence TLC measurements in dogs with elbow OA. CLINICAL SIGNIFICANCE: Sedation or GA can cause slight alterations to goniometric measurements in canine elbows with OA. The protocols used in this study for sedation and GA seem interchangeably acceptable for goniometry and TLC measurements in dogs with elbow OA.