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Ameloblastoma (AB) is an odontogenic tumor that arises from ameloblast-lineage cells. Although relatively uncommon and rarely metastatic, AB tumors are locally invasive and destructive to the jawbone and surrounding structures. Standard-of-care surgical resection often leads to disfigurement, and many tumors will locally recur, necessitating increasingly challenging surgeries. Recent genomic studies of AB have uncovered oncogenic driver mutations, including in the mitogen-activated protein kinase (MAPK) and Hedgehog signaling pathways. Medical therapies targeting those drivers would be a highly desirable alternative or addition to surgery; however, a paucity of existing AB cell lines has stymied clinical translation. To bridge this gap, here we report the establishment of 6 new AB cell lines—generated by “conditional reprogramming”—and their genomic characterization that reveals driver mutations in FGFR2, KRAS, NRAS, BRAF, PIK3CA, and SMO. Furthermore, in proof-of-principle studies, we use the new cell lines to investigate AB oncogene dependency and drug sensitivity. Among our findings, AB cells with KRAS or NRAS mutation (MAPK pathway) are exquisitely sensitive to MEK inhibition, which propels ameloblast differentiation. AB cells with activating SMO-L412F mutation (Hedgehog pathway) are insensitive to vismodegib; however, a distinct small-molecule SMO inhibitor, BMS-833923, significantly reduces both downstream Hedgehog signaling and tumor cell viability. The novel cell line resource enables preclinical studies and promises to speed the translation of new molecularly targeted therapies for the management of ameloblastoma and related odontogenic neoplasms.

Objective:Efforts to improve the nutritional quality and health promotion in the charitable food system have been undertaken. Though methods exist to track these efforts in terms of food banks’ inventory, there are not research-tested tools to assess, monitor and influence policy, systems and environmental (PSE) changes. The study objective was to develop and evaluate a novel assessment tool that could be used to evaluate a food bank’s efforts to improve the promotion of health and nutritious foods.Design:The study had five phases: (1) initial development; (2) iterative review and revisions; (3) pilot testing; (4) content validity assessment and (5) inter-rater and test-retest assessment. The Food Bank Health and Nutrition Assessment (FB-HANA) was drafted after reviewing existing policies, nutrition-focused charitable food systems guidance and similar tools for food pantries.Setting:Midwestern United States.Participants:Eleven food banks.Results:Stakeholders and pilot testers provided initial feedback to refine the FB-HANA’s flow, ease of completion and collection of contextual information. External experts rated the FB-HANA and each of the eight objectives as content valid. A set of two assessments completed by twenty-six community-based professionals, employed by Extension and fourteen food bank staff across eleven food banks, supported moderate to excellent inter-rater and test-retest reliability for the FB-HANA overall and each of its objectives.Conclusions:Evidence suggests that the FB-HANA can be used by either food bank or community-based professionals, such as Extension staff, to provide a perspective on ways food banks promote health and nutrition through PSE approaches.

Schizophrenia (SZ) is characterized by neurobiological and associated cognitive and functional deficits, including pronounced cortical thinning, that lead to acute and long-term functional impairment. Research with older adults supports the role of non-pharmacological interventions, such as exercise (E) and cognitive training (CT), for cognitive impairments. This literature influenced the development of combined CTE treatments for individuals with SZ. However, the impact of longer combined treatment duration (6 months) on neuroanatomy has yet to be explored in patients in the early course of the illness. The impact of adding exercise to cognitive training for key brain regions associated with higher-order cognition was examined here using magnetic resonance imaging (MRI) in first-episode psychosis (FEP) patients.UCLA Aftercare Research Program patients with a recent first episode of schizophrenia were randomly assigned to either combined cognitive and exercise training (CTE) (N = 20) or cognitive training alone (CT) (N = 17) intervention. Cortical thickness was measured longitudinally and analyzed for two regions of interest using FreeSurfer.Compared to patients in the CT group, those in the CTE group demonstrated an increase in cortical thickness within the left anterior cingulate cortex over the six-month treatment period (ACC: FThese findings suggest that exercise and cognitive training may synergistically increase fronto-cingulate cortical thickness to mitigate progressive neural atrophy in the early course of SZ. This combined intervention appears to be a valuable adjunct to standard pharmacologic treatment in FEP patients.

The Cambrian olenid trilobite Peltura Milne-Edwards, 1840 is widespread in the Furongian strata of the Cambrian continents of Baltica and Avalonia, and has played a significant role in biostratigraphic zonations for both regions. Despite this importance, the genus is poorly known in Avalonian Canada. New collections from the Chelsey Drive Group on Cape Breton Island, Nova Scotia, yielded numerous sclerites of a new species, Peltura hutchinsoni sp. nov., that may also occur in the Parabolina lobata Zone of Baltica. Archival specimens from Sweden and Norway allow the revision of Peltura scarabaeoides ( Wahlenberg, 1821 ) and Peltura acutidens Brögger, 1882 , respectively.

Introduction Testosterone plays an important role in collagen metabolism, TGF-β1 expression, and wound healing, all critical factors in the pathogenesis of Peyronie’s disease (PD). While evidence is mixed, some clinical studies have suggested an association between PD and hypogonadism. Objective We seek to investigate whether baseline total serum testosterone (tT) influences response to intralesional collagenase clostridium histolyticum (CCh) for PD. Methods A retrospective review of patients undergoing CCh injections was conducted at a single institution. Only patients with available tT levels within one year of initial CCh injection were included. Curvature was assessed after in-office intracavernosal injection of vasodilatory agents or patient-provided photograph. Data was collected on baseline demographic characteristics, hypogonadal status, tT, number of CCh cycles, and pre- and post-treatment degree of curvature. Hypogonadism was defined as a tT Results A total of 36 men were included. The mean age was 58.2 years old (SD 10.4) and the mean BMI was 26.8 (SD 3.2). The mean pre-treatment tT was 459.2 ng/dL (SD 144.0), and 14 (39.9%) were hypogonadal. Of hypogonadal men, 5 (35.7%) were receiving hormonal replacement therapy, 4 on testosterone and 1 on clomiphene. Thirty (83.3%) men experienced some degree of erectile dysfunction. The mean pre-treatment curvature was 47.6° (SD 14.2) and the mean post-treatment curvature was 27.8°(SD 10.7), for a mean improvement of 19.9° (40.1%) after an average of 4 cycles (2-8) (Table 1). Baseline tT was not associated with baseline rigidity (β=-0.01; R2=0.02; p=0.41). However, hypogonadal status was significantly associated with more severe curvature, 54.6° among hypogonadal men compared to 43.2° among eugonadal men (p=0.03); however, baseline curvature and tT were not significantly associated (β=-0.03; R2=0.09; p=0.08). On linear regression analysis, tT did not significantly predict improvement in degrees (β=-0.02; R2=0.06; p=0.14; Figure 1) or percent (β=0.0; R2=0.05; p=0.18; Figure 2). Similarly, improvement in neither degrees nor percent differed significantly by hypogonadal status (p=0.14 and p=0.69, respectively). Number of cycles did significantly predict greater improvement in curvature on both univariate and multivariate analyses (β=5.7; R2=0.34; p Conclusions While hypogonadism is associated with more severe curvature, neither total testosterone nor hypogonadism is associated with degree of improvement after CCh treatment. Men should be offered CCh therapy according to guidelines independent of gonadal status. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast Clarus Therapeutics Antares Pharma Acerus.

Background Women are at risk for weight gain during the transition to menopause, but few have examined the contribution of menopause to weight gain in women with human immunodeficiency virus (WWH). Methods From 2000 to 2013, participants (621 WWH; 218 without HIV [WWOH]) from the Women's Interagency HIV Study were categorized by menopausal phase using serial measures of anti-Müllerian hormone (AMH). Multivariable linear mixed models examined the association of menopausal phase with body mass index (BMI) and waist circumference (WC) trajectory, stratified by HIV status. Results In models controlled for chronologic age, the estimated effects (95% confidence interval) of menopausal phase on annual rate of BMI change across early perimenopause, late perimenopause, and menopause, respectively, compared to premenopause were −0.55% (−.80 to −.30), −0.29% (−.61 to .03), and −0.67% (−1.12 to −.20) in WWH, whereas estimated effects were 0.43% (−.01 to .87) and 0.15% (−.42 to .71) across early and late perimenopause, respectively, and −0.40% (−1.24 to .45) across menopause in WWOH. The estimated effects on rate of WC change were negative across early perimenopause (−0.21% [−.44 to .03]) and menopause (−0.12% [−.5 to .26]) and positive across late perimenopause (0.18% [−.10 to .45]) in WWH, and positive across all 3 menopausal phases in WWOH, but these effects were not statistically significant. Conclusions In WWH, the menopausal transition was associated with BMI and WC trajectories that were mostly in a negative direction and opposite from WWOH after adjusting for age, suggesting that HIV blunts weight gain during the menopausal transition.

Contexte. La pandémie de COVID-19 a imposé une réorganisation rapide des services de santé. Les patients sont exposés à des risques importants de dommages associés aux soins. L’interruption totale des services de soins pendant la pandémie a contribué à accroître ces risques. Objectif. Le type et la nature des incidents liés à la sécurité des patients (i.e. événements indésirables) en soins de premier recours en France au cours de la première vague de COVID-19 a été exploré afin de formuler des recommandations provisoires en vue d’améliorations. Méthodes. Une enquête nationale de déclaration des incidents liés à la sécurité des patients a été envoyée aux médecins généralistes français le 28 avril 2020. Les déclarations ont été codées à l’aide d’un système de classification aligné sur la classification internationale pour la sécurité des patients de l’OMS (types d’incidents, facteurs contributifs, résultats de l’incident et gravité du préjudice). L’analyse a impliqué le codage des données, leur traitement, la génération itérative de résumés de données à l’aide d’une analyse statistique descriptive et thématique. Clinicaltrials.gov : NCT04346121. Résultats. Sur 132 incidents, 58 (44 %) étaient liés à des retards de diagnostic, d’évaluation et d’orientation. Des annulations de rendez-vous, d’hospitalisations ou de procédures ont été signalées dans 22 (17 %) de ces incidents. Les incidents liés au confinement à domicile ont fait l’objet de 15 déclarations (10 %), et l’arrêt inapproprié de médicaments de cinq déclarations (4 %). Les patients ont retardé leur consultation ou n’ont pas consulté leur médecin généraliste ou d’autres professionnels de santé par crainte de contracter une infection à la COVID-19 dans 26 (10 %) incidents, ou par crainte de surcharger leur médecin généraliste dans huit (3 %) incidents. Conclusion. Les contraintes découlant de la première vague de la pandémie de COVID-19 ont contribué aux incidents liés à la sécurité des patients lors d’affections non liées à la COVID-19. Les leçons tirées de ces incidents mettent en évidence les domaines dans lesquels les services de soins de premier recours en France peuvent concentrer leurs ressources pour concevoir des systèmes plus sûrs pour les patients.

The presence of a genetic condition is a risk factor for increased mortality in hypoplastic left heart syndrome (HLHS). Speckle tracking strain analysis in interstage echocardiograms have shown promise in identifying patients with HLHS at increased risk of mortality. We hypothesized that fetuses with a genetic condition and HLHS have impaired right ventricular global longitudinal strain compared with fetuses with HLHS and no evident genetic condition. We performed a retrospective analysis of 60 patients diagnosed in fetal life with HLHS from 11/2015 to 11/2019. We evaluated presenting echocardiograms and calculated right ventricular global longitudinal strain (RV GLS) and fractional area of change (FAC) using post-processing software. We first compared RV GLS and FAC between those with genetic conditions to those without. We examined the secondary outcome of mortality among those with and without genetic conditions and among HLHS subgroups. Of the 60 patients with available genetic testing, 11 (18%) had an identified genetic condition. Neither RV GLS nor FAC was significantly different between patients with and without genetic conditions. There was no difference in RV GLS or FAC among HLHS phenotype or those who died or survived as infants. However, patients with a genetic syndrome had increased neonatal and overall mortality. In this cohort, RV GLS did not differ between those with and without a genetic diagnosis, among HLHS phenotypes, or between those surviving and dying as infants. Further analysis of strain throughout gestation and after birth could provide insight into the developing heart in fetuses with HLHS.

Background Merkel cell carcinoma (MCC) is a rare malignant cutaneous tumor with frequent metastases. They often appear in the face where cosmetic and functional outcome is critical. Mohs micrographic surgery (MMS) is a controlled intervention that optimizes negative margins without sacrificing tissue. Objective A comprehensive assessment of outcomes of MMS-treated facial MCC will help guide clinicians in surgical and medical management. Methods & Materials Retrospective review identified facial MCC cases treated with MMS at a single institution from January 2005 to August 2020. Tumor characteristics and outcomes were recorded and descriptive and predictive analyses were performed. Results 34 cases were reviewed with a mean followup of 34.4 months. The most common sites were the forehead, cheek-jaw region, and nasal ala. 2 (5.9%) patients had local recurrence by a mean of 4.3 months. No documented variables were significantly associated with local recurrence. 8 (23.5%) patients had progression to metastasis by a mean of 9.4 months. Younger age at biopsy and surgery, male sex, and intraoperative detection of in-transit disease were significantly associated with progression to metastasis. Conclusions In summary, the tissue-sparing approach of MMS may be beneficial for MCC in cosmetically and functionally sensitive facial locations as it preserves tissue without compromising outcomes.

This chapter will advance understanding on how leadership learning occurs in graduate and professional school contexts and suggests how social class should be considered in the planning, implementation, and outcomes of preparing individuals to lead in their fields of choice.

Resume Position du probleme La consommation des antidepresseurs chez les enfants et les adolescents est en augmentation en France, bien que leur recommandation d’utilisation soit restreinte du fait des effets indesirables auxquels ils sont associes. L’objectif de cette etude etait de decrire les caracteristiques des delivrances des antidepresseurs chez les enfants et les adolescents en Midi-Pyrenees. Methode Les donnees ont ete extraites a partir de leurs codes ATC du systeme national des donnees de sante (SNDS) pour la region Midi-Pyrenees. Tous les remboursements d’antidepresseurs, de benzodiazepines et de neuroleptiques entre janvier 2015 et juin 2017 chez les patients âges de 6 a 17 ans (enfant : 6 a 11 ans, adolescents : 12 a 17 ans) ont ete analyses puis les donnees concernant les antidepresseurs ont ete selectionnees. La population a ete repartie en sous-groupes en fonction de l’âge. Resultats Au cours des 30 mois analyses, 12 783 antidepresseurs ont ete delivres a 3506 patients. Les antidepresseurs etaient plus delivres (90 %) aux adolescents. En termes de prevalence, 24,7 % des enfants ont eu au moins une delivrance d’amitriptyline et 31,2 % des adolescents avaient eu au moins une delivrance de sertraline. En termes de nombre de delivrances, la sertraline etait l’antidepresseur le plus delivre aux enfants (26,9 % et aux adolescents (40,7 %). La delivrance d’une benzodiazepine avec un antidepresseur concernait 35,1 % des enfants et des adolescents. Conclusion L’amitriptyline a la plus forte prevalence de delivrance chez les enfants et la sertraline chez les adolescents. Pourtant, la fluoxetine est recommandee en premiere intention dans la depression pour cette population. La mise en ligne d’un site d’aide a la prescription des psychotropes de type psychotropes.fr a destination du medecin generaliste devrait ameliorer l’application des recommandations de pratique clinique.

Background: There is growing recognition of the psychosocial burden of caregiving on relative caregivers of the mentally ill in low-and middle-income countries. Yet there remains limited formal research examining the challenges and psychosocial support needs of these relative caregivers, particularly with sensitivity to understanding caregiver experiences across diverse cultures and contexts. The purpose of this study was to study caregiver burden to inform potential intervention approaches among relative caregivers of treatment-engaged mentally ill patients in Cambodia. Methods: Participants were all relative caregivers identified through their connection to a non-governmental organization providing psychiatric care. Five focus group discussions were held with 37 participants to explore challenges experienced by relative caregivers. A total of 115 caregivers then completed a mental health assessment consisting of the Patient Health Questionnaire – 9 item scale, Generalized Anxiety Disorder – 7-item scale, and 21-item Depression, Anxiety, and Stress Scale. Internal consistencies ranged from α = .81 to .87 across scales. Results: Five themes emerged from the focus group discussions: financial burden, erratic behavior of patients, social alienation, somatic and emotional symptoms, and barriers to help-seeking. Assessment data indicated the sample was highly symptomatic. Women and those with no employment appeared to be at higher risk of distress, as were those caregivers with a biological relationship to the patient (parents, children, and siblings; relative to spouses or other relationships). Discussion: Findings suggest a need for regular screening and greater psychosocial support for relative caregivers. It is notable that the needs identified within the current study remain prominent even as this is a treatment-engaged sample.

Anywhere from 16% to 37% of patients undergoing bariatric and metabolic surgery are estimated to have a hiatal hernia. To address the lack of long-term data showing the efficacy of bioabsorbable mesh in reducing the recurrence of hiatal hernia in patients who undergo bariatric surgery, we evaluated the world literature and performed a meta-analysis.To evaluate hiatal hernia recurrence rates after placement of bioabsorbable mesh in bariatric patients.Meta-analysis of world literature.We performed a literature search using PubMed and MEDLINE with search terms including "hiatal hernia recurrence," "bariatric surgery," "bioabsorbable mesh," "Gore BIO-A," and "trimethylene carbonate." Analysis was conducted to compare surgical time, length of stay, recurrence rate, hernia size, and changes in body mass index before and after surgery between mesh-group (MG) and nonmesh (NM) patients. The meta-analysis was described using standardized mean difference, weighted mean difference, effect size, and 95% confidence interval (CI). An ITwelve studies with 1351 patients were included in our meta-analysis. Four studies had both an MG and an NM group. There were 668 patients in the MG and 683 patients in the NM group. Hernia size noted in the NM group (7 cmRepair with bioabsorbable mesh at the time of the index bariatric surgery is more effective at reducing the recurrence rate of hiatal hernia than suture cruroplasty. Further studies investigating the long-term outcomes of bioabsorbable mesh placed at the time of bariatric surgery are needed.