Bridging the gap between in vitro and in vivo models: a way forward to clinical translation of mitochondrial transplantation in acute disease states.

Mitochondrial transplantation and transfer are being explored as therapeutic options in acute and chronic diseases to restore cellular function in injured tissues. To limit potential immune responses and rejection of donor mitochondria, current clinical applications have focused on delivery of autologous mitochondria. We recently convened a Mitochondrial Transplant Convergent Working Group (CWG), to explore three key issues that limit clinical translation: (1) storage of mitochondria, (2) biomaterials to enhance mitochondrial uptake, and (3) dynamic models to mimic the complex recipient tissue environment.

The utility of the abdominal series in the emergency setting: a retrospective review.

Purpose: The abdominal series (AXR) remains a frequently ordered test in the emergency department (ED), despite existing literature questioning its utility. The aim of this study was to characterize the use of the AXR in the ED by quantifying how often it is ordered and the frequency of subsequent imaging. Additionally, a time estimate in ED associated with the AXR was quantified.

Headache Over Heels: CT Negative Subarachnoid Hemorrhage.

Audience: This simulation is intended for MS4 or PGY-1 learners.

Introduction: Both headache and syncope are common chief complaints in the emergency department (ED); however, subarachnoid hemorrhage (SAH) is uncommon (accounting for 1-3% of all patients presenting to the ED with headache), with near 50% mortality.1-3 It is important to recognize the signs and symptoms that point to this specific diagnosis.

Mitochondrial transplant after ischemia reperfusion promotes cellular salvage and improves lung function during ex-vivo lung perfusion.

Background: In lung transplantation, ischemia-reperfusion injury associated with mitochondrial damage can lead to graft rejection. Intact, exogenous mitochondria provide a unique treatment option to salvage damaged cells within lung tissue.

Methods: We developed a novel method to freeze and store allogeneic mitochondria isolated from porcine heart tissue.

Topical treatment of actinic keratoses in organ transplant recipients: a feasibility study for SPOT (Squamous cell carcinoma Prevention in Organ transplant recipients using Topical treatments).

Background: The risk of cutaneous squamous cell carcinoma (cSCC) is significantly increased in organ transplant recipients (OTRs). Clearance of actinic keratoses (AKs) is generally regarded as a surrogate biomarker for cSCC prevention. OTR-cSCC chemoprevention with topical AK treatments has not been investigated in randomized controlled trials (RCTs), although there is evidence that 5% 5-fluorouracil (5-FU) may be chemoprotective in immunocompetent patients.

Mesenchymal stromal cell-derived extracellular vesicles reduce lung inflammation and damage in nonclinical acute lung injury: Implications for COVID-19.

Mesenchymal stem cell derived extracellular vesicles (MSC-EVs) are bioactive particles that evoke beneficial responses in recipient cells. We identified a role for MSC-EV in immune modulation and cellular salvage in a model of SARS-CoV-2 induced acute lung injury (ALI) using pulmonary epithelial cells and exposure to cytokines or the SARS-CoV-2 receptor binding domain (RBD). Whereas RBD or cytokine exposure caused a pro-inflammatory cellular environment and injurious signaling, impairing alveolar-capillary barrier function, and inducing cell death, MSC-EVs reduced inflammation and reestablished target cell health.

Interventions for basal cell carcinoma of the skin.

Background: Basal cell carcinoma (BCC) is the commonest cancer affecting white-skinned individuals, and worldwide incidence is increasing. Although rarely fatal, BCC is associated with significant morbidity and costs. First-line treatment is usually surgical excision, but alternatives are available.

Slow-oscillation activity is reduced and high frequency activity is elevated in older adults with insomnia.

Study Objectives: High-frequency electroencephalographic activity (> 16 Hz activity) is often elevated during nonrapid eye movement sleep among individuals with insomnia, in line with the hyperarousal theory of insomnia. Evidence regarding sleep depth marked by slow-wave activity (< 4 Hz) is more mixed. Distinguishing subcomponents of slow-wave activity (slow-oscillation [< 1 Hz] or delta activity [1-4 Hz)]) may be critical in understanding these discrepancies, given that these oscillations have different neural generators and are functionally distinct.

Rate of Nondiagnostic Computerized Tomography Pulmonary Angiograms (CTPAs) Performed for the Diagnosis of Pulmonary Embolism in Pregnant and Immediately Postpartum Patients.

Objective: To evaluate the nondiagnostic rate of computed tomography pulmonary angiography (CTPA) in pregnant and postpartum patients with suspected pulmonary embolism (PE) to determine whether CTPA or ventilation-perfusion (VQ) scan should be considered first line imaging in this patient population considering their equivalent accuracy and the greater radiation exposure to proliferating breast tissue of CTPA.

Methods: All pregnant/postpartum female patients between 18 and 50 years of age who had CTPA within the Eastern Health Authority between November 2012 and November 2016 were included. Each scan was evaluated for nondiagnosis based on two criteria: contrast density in the main pulmonary artery, and respiratory motion artefact.

Mesenchymal stromal cell-derived exosomes improve mitochondrial health in pulmonary arterial hypertension.

Secreted exosomes are bioactive particles that elicit profound responses in target cells. Using targeted metabolomics and global microarray analysis, we identified a role of exosomes in promoting mitochondrial function in the context of pulmonary arterial hypertension (PAH). Whereas chronic hypoxia results in a glycolytic shift in pulmonary artery smooth muscle cells (PASMCs), exosomes restore energy balance and improve O consumption.

Assessing the Prevalence of Incidental Findings Identified by CTPA in Women of Reproductive Age.

Background And Objective: Though multiple studies have evaluated the prevalence of incidental findings identified by CTPA, none have done so with a focus on reproductive-age females with normal chest X-ray (CXR). Due to a comparatively lower breast radiation dose, the oft-recommended alternative to CTPA in this patient group is a V/Q scan. However, these are limited in their assessment of these alternate findings; therefore, it is of particular importance to evaluate the likelihood of these findings on CT in this patient group, which is the goal of this study.

Outcomes of early intervention for deaf children with additional needs following an Auditory Verbal approach to communication.

Objectives: To determine and compare the rates of progress made by pre-school aged children with all degrees and types of hearing impairment and deafness, both with and without additional needs as catalogued using SNOMED CT, at the end of a non-statutory programme of individualised Auditory Verbal (AV) intervention.

Methods: An audit was conducted using a retrospective and comparative study design to examine spoken language outcomes in children who had spent more than two years on an AV programme and had completed their programmes between January 2007 and December 2017. The children were stratified according to i) whether they achieved age appropriate language (AAL) (n =102) or not (n =27); ii) whether they had deafness alone (n = 77) or deafness with additional needs (n =52); and iii) whether children with additional needs achieved AAL (n= 27) or not (n =25).

WhatsApp platforms in tropical public health resource-poor settings.

In order to deliver equal healthcare access to resource-poor settings, sustainable, cost-effective systems of communication should be used. As mobile phone use increases, remote care can be delivered via teledermatology using Apps. This commentary covers how WhatsApp could be used by dermatologists seeking to deliver healthcare in this context.

The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature.

Cutaneous squamous cell carcinoma (cSCC) has a high tumour mutational burden (50 mutations per megabase DNA pair). Here, we combine whole-exome analyses from 40 primary cSCC tumours, comprising 20 well-differentiated and 20 moderately/poorly differentiated tumours, with accompanying clinical data from a longitudinal study of immunosuppressed and immunocompetent patients and integrate this analysis with independent gene expression studies. We identify commonly mutated genes, copy number changes and altered pathways and processes.

Bcl-xL dependency coincides with the onset of neurogenesis in the developing mammalian spinal cord.

The bcl-2 family of survival and death promoting proteins play a key role in regulating cell numbers during nervous system development. Bcl-x, an anti-apoptotic bcl-2 family member is highly expressed in the developing nervous system. However; the early embryonic lethality of the bcl-x germline null mouse precluded an investigation into its role in nervous system development.

Decorin and colchicine as potential treatments for post-haemorrhagic ventricular dilatation in a neonatal rat model.

Background: Post-haemorrhagic ventricular dilatation (PHVD) after intraventricular haemorrhage (IVH) remains a significant problem in preterm infants. Due to serious disadvantages of ventriculoperitoneal shunt dependence, there is an urgent need for non-surgical interventions. Considerable experimental and clinical evidence implicates transforming growth factor β (TGFβ) in the pathogenesis of PHVD.

In vitro praziquantel test capable of detecting reduced in vivo efficacy in Schistosoma mansoni human infections.

Although great reductions in human schistosomiasis have been observed after praziquantel (PZQ) mass drug administration (MDA), some individuals remain infected after multiple treatments. Many MDA programs now require monitoring for drug efficacy as a key component. No molecular tools for PZQ resistance currently exist and investigations into the dose of PZQ required to kill 50% of adult worms in vivo (ED(50)) present ethical, logistical, and temporal restraints.

The importance of indirect cues for white-browed sparrow-weaver (Plocepasser mahali) risk assessment.

Both direct cues that provide information about the actual presence of a predator and indirect environmental cues that provide information about the probability of encountering a predator may be used by animals assessing predation risk, but relatively few studies manipulate both simultaneously to study their relative importance. We conducted two experiments to study the foraging decisions of white-browed sparrow-weavers (Plocepasser mahali). The first experiment manipulated both direct and indirect cues in a feeding array by simultaneously placing feeding stations at different distances from humans (to manipulate direct risk) and from protective cover (to manipulate indirect risk).

Students' perceptions of effective learning experiences in dental school: a qualitative study using a critical incident technique.

Students' views of their educational experience can be an important source of information for curriculum assessment. Although quantitative methods, particularly surveys, are frequently used to gather such data, fewer studies have employed qualitative methods to examine students' dental education experiences. The purpose of this study is to explore characteristics of effective learning experiences in dental school using a qualitative method.

Effects of otitis media with effusion (OME) on central auditory function.

Conductive hearing loss attenuates and delays sound passing through the middle ear. This impairs binaural hearing and other central auditory functions dependent on high fidelity sound transmission. Persistent conductive loss leads to central impairments that persist after the peripheral loss has resolved.

Impaired binaural hearing in children produced by a threshold level of middle ear disease.

Otitis media with effusion (OME), a form of middle ear disease, is the most common reason for young children both to visit their family doctor and to have surgery. Almost all children have at least a single episode of OME before their first birthday and annual incidence rates exceed 50% in each of the first five years. For most children, OME occurs infrequently, but about 10-15% of children have OME during more than half of their first six years.