An epigenetic signature for monoallelic olfactory receptor expression.

Constitutive heterochromatin is traditionally viewed as the static form of heterochromatin that silences pericentromeric and telomeric repeats in a cell cycle- and differentiation-independent manner. Here, we show that, in the mouse olfactory epithelium, olfactory receptor (OR) genes are marked in a highly dynamic fashion with the molecular hallmarks of constitutive heterochromatin, H3K9me3 and H4K20me3. The cell type and developmentally dependent deposition of these marks along the OR clusters are, most likely, reversed during the process of OR choice to allow for monogenic and monoallelic OR expression. In contrast to the current view of OR choice, our data suggest that OR silencing takes place before OR expression, indicating that it is not the product of an OR-elicited feedback signal. Our findings suggest that chromatin-mediated silencing lays a molecular foundation upon which singular and stochastic selection for gene expression can be applied.

Pediatric cochlear implantation: Early surgical intervention and parental quality of life.

OBJECTIVES: Pediatric cochlear implantation (CI) provides sound perception to children with significant sensorineural hearing loss and, despite its challenging process, early implantation can enhance children's speech/language outcomes and potentially improve parental quality of life (PQoL). This study aims to examine parental perspectives on quality of life and parenting children with CI. METHODS: This study combined retrospective chart review and parent reported outcomes. Data were abstracted from medical charts of 85 children who underwent CI between 2016 and 2022 at a tertiary pediatric hospital. Parents were administered the Acceptance and Action Questionnaire (AAQ-MCHL), an 8-item self-report assessment of quality of life for parents of children with CI. Multivariate linear regression analyses examined clinical factors associated with PQoL scores. RESULTS: Parents whose children were implanted at less than two years of age reported significantly higher PQoL, indicated by lower AAQ scores, with a mean AAQ-MCHL of 7.6 + 5.7. In contrast, implantation at age >2 years yielded a mean AAQ-MCHL of 16.2 + 9.6. Parents interviewed within one year post-surgery reported lower PQoL, with a mean AAQ-MCHL of 12.3 + 8.8 compared to those interviewed after one year, with 20.5 + 10.4. CONCLUSION: Early identification of profound hearing loss in children, coupled with early surgical CI, may be associated with higher parental quality of life. The beneficial outcomes appear to be potentiated over time. Further research is essential to fully comprehend the impact of CI on the quality of life of children and their parents.

Rapid assessment of changes in phage bioactivity using dynamic light scattering.

Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. Here, we use Dynamic Light Scattering (DLS) to measure changes in phage physical state in response to environmental factors and time, finding that phages tend to decay and form aggregates and that the degree of aggregation can be used to predict phage bioactivity. We then use DLS to optimize phage storage conditions for phages from human clinical trials, predict bioactivity in 50-year-old archival stocks, and evaluate phage samples for use in a phage therapy/wound infection model. We also provide a web-application (Phage-ELF) to facilitate DLS studies of phages. We conclude that DLS provides a rapid, convenient, and non-destructive tool for quality control of phage preparations in academic and commercial settings.

Cardiovascular hemodynamics in mice with tumor necrosis factor receptor-associated factor 2 mediated cytoprotection in the heart.

Introduction: Many studies in mice have demonstrated that cardiac-specific innate immune signaling pathways can be reprogrammed to modulate inflammation in response to myocardial injury and improve outcomes. While the echocardiography standard parameters of left ventricular (LV) ejection fraction, fractional shortening, end-diastolic diameter, and others are used to assess cardiac function, their dependency on loading conditions somewhat limits their utility in completely reflecting the contractile function and global cardiovascular efficiency of the heart. A true measure of global cardiovascular efficiency should include the interaction between the ventricle and the aorta (ventricular-vascular coupling, VVC) as well as measures of aortic impedance and pulse wave velocity. Methods: We measured cardiac Doppler velocities, blood pressures, along with VVC, aortic impedance, and pulse wave velocity to evaluate global cardiac function in a mouse model of cardiac-restricted low levels of TRAF2 overexpression that conferred cytoprotection in the heart. Results: While previous studies reported that response to myocardial infarction and reperfusion was improved in the TRAF2 overexpressed mice, we found that TRAF2 mice had significantly lower cardiac systolic velocities and accelerations, diastolic atrial velocity, aortic pressures, rate-pressure product, LV contractility and relaxation, and stroke work when compared to littermate control mice. Also, we found significantly longer aortic ejection time, isovolumic contraction and relaxation times, and significantly higher mitral early/atrial ratio, myocardial performance index, and ventricular vascular coupling in the TRAF2 overexpression mice compared to their littermate controls. We found no significant differences in the aortic impedance and pulse wave velocity. Discussion: While the reported tolerance to ischemic insults in TRAF2 overexpression mice may suggest enhanced cardiac reserve, our results indicate diminished cardiac function in these mice.

Rapid assessment of changes in phage bioactivity using dynamic light scattering.

Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. In this study, we use dynamic light scattering (DLS) to measure changes in phage physical state in response to environmental factors and time, finding that phages tend to decay and form aggregates and that the degree of aggregation can be used to predict phage bioactivity. We then use DLS to optimize phage storage conditions for phages from human clinical trials, predict bioactivity in 50-y-old archival stocks, and evaluate phage samples for use in a phage therapy/wound infection model. We also provide a web application (Phage-Estimator of Lytic Function) to facilitate DLS studies of phages. We conclude that DLS provides a rapid, convenient, and nondestructive tool for quality control of phage preparations in academic and commercial settings.

Evaluating delays for emergent CT scans from a rural British Columbia hospital.

OBJECTIVES: Computed Tomography (CT) scans help diagnose and triage life-threatening and time-sensitive emergency conditions, but most rural hospitals in British Columbia do not have access to a local CT scanner. We investigate how many transfers from a rural British Columbia hospital were for CT scans and describe the time delays to emergent CT imaging. METHODS: This was a prospective cohort study, over a 1-year period, on all patients requiring a transfer from the Golden and District Hospital, located 247 km from the closest CT scanner. Data collection forms were completed prospectively and the main measurements included age, transport triage level, reason for transfer, referral hospital, transfer request time, and CT scan time. The time interval between the CT request and CT imaging was calculated and represents the 'delay to CT scan' interval. RESULTS: The study hospital received 8672 emergency department (ED) visits and 220 were transferred to referral centres (2.5%). 61% of all transfers received a CT scan. Transfers for time-sensitive emergencies took an average of 6 h 52 min. Patients with acute stroke experienced a 4 h 44 min time interval. Less urgent and non-urgent conditions entailed an even greater time delay. CONCLUSIONS: This study highlights that the lack of a rural CT scanner is associated with increased transfers and significant time delays. Improving access to CT scanners for rural communities may be one of the many steps in addressing healthcare disparities between rural and urban communities.

RéSUMé: OBJECTIFS: La tomodensitométrie (TDM) aide à diagnostiquer et à trier les situations d'urgence qui mettent la vie en danger et pour lesquelles le temps est compté, mais la plupart des hôpitaux ruraux de la Colombie-Britannique n'ont pas accès à un tomodensitomètre local. Nous enquêtons sur le nombre de transferts d'un hôpital rural de la Colombie-Britannique pour des tomodensitogrammes et nous décrivons les délais pour l'imagerie tomographique émergente. MéTHODES: Il s'agit d'une étude de cohorte prospective, sur une période d'un an, sur tous les patients nécessitant un transfert de l'hôpital de Golden and district, situé à 247 km du scanner le plus proche. Les formulaires de collecte de données ont été remplis de manière prospective et les principales mesures comprenaient l'âge, le niveau de triage de transport, la raison du transfert, l'hôpital de référence, le temps de demande de transfert et le temps de tomodensitométrie. L'intervalle de temps entre la demande de tomodensitométrie et l'imagerie par tomodensitométrie a été calculé et représente l'intervalle « retard au scanner¼. RéSULTATS: L'hôpital d'étude a reçu 8 672 visites aux services d'urgence (SU) et 220 ont été transférés aux centres d'aiguillage (2,5%). 61% de tous les transferts ont fait l'objet d'un scanner. Les transferts pour les urgences sensibles au facteur temps ont pris en moyenne 6 h 52. Les patients ayant subi un accident vasculaire cérébral aigu ont connu un intervalle de temps de 4 h 44. Des conditions moins urgentes et non urgentes ont entraîné un délai encore plus long. CONCLUSIONS: Cette étude met en évidence que l'absence de tomodensitomètre en milieu rural est associée à une augmentation des transferts et à des retards importants. L'amélioration de l'accès aux tomodensitomètres pour les communautés rurales peut être l'une des nombreuses étapes pour remédier aux disparités en matière de soins de santé entre les communautés rurales et urbaines.

CPRural.

INTRODUCTION: The purpose of our study was to determine if regular cardiopulmonary resuscitation (CPR) practise improved the quality of nurses' chest compressions in a rural hospital. METHODS: The study was a prospective interventional trial measuring the effectiveness of brief, monthly CPR practice for rural nurses. The quality of nurses' chest compressions was measured before and after monthly practise with an interactive feedback device at the Golden and District Hospital, a rural facility in BC. RESULTS: All three components of high-quality CPR (depth, recoil and rate) improved significantly. CONCLUSION: Monthly practise of chest compressions with an interactive feedback device improved the quality and confidence of nurses' CPR skills. These results suggest that a higher frequency of CPR practice (than the minimum annual recertification) would improve both the quality and retention of CPR skills, specifically for low-volume rural hospitals.

Résumé Introduction: Notre étude visait à déterminer si la pratique régulière de la réanimation cardio-respiratoire (RCR) améliore la qualité des compressions thoraciques réalisées par le personnel infirmier dans un hôpital en région rurale. Méthodes: Il s'agit d'une étude interventionnelle prospective ayant mesuré l'efficacité de la brève pratique mensuelle de la RCR par le personnel infirmier des régions rurales. La qualité des compressions thoraciques effectuées par le personnel infirmier a été mesurée avant et après la pratique mensuelle avec un dispositif interactif de rétroaction à l'hôpital Golden and District; un établissement situé en région rurale de la Colombie-Britannique. Résultats: Les trois éléments de la RCR de grande qualité (profondeur, relaxation et rythme) se sont considérablement améliorés. Conclusion: La pratique mensuelle des compressions thoraciques avec un dis- positif interactif de rétroaction a permis d'améliorer la qualité des compétences en RCR du personnel infirmier et la confiance en ces compétences. Ces résultats laissent croire que la plus grande fréquence de la pratique de la RCR (plutôt que le renouvellement annuel minimal de la certification) améliorerait la qualité et la rétention des compétences en RCR, en particulier dans les hôpitaux des régions rurales à faible volume. Keywords: Réanimation cardio-respiratoire, réanimation cardio-pulmonaire, compressions thoraciques.