Interorganelle communication, aging, and neurodegeneration.

Our cells are comprised of billions of proteins, lipids, and other small molecules packed into their respective subcellular organelles, with the daunting task of maintaining cellular homeostasis over a lifetime. However, it is becoming increasingly evident that organelles do not act as autonomous discrete units but rather as interconnected hubs that engage in extensive communication through membrane contacts. In the last few years, our understanding of how these contacts coordinate organelle function has redefined our view of the cell. This review aims to present novel findings on the cellular interorganelle communication network and how its dysfunction may contribute to aging and neurodegeneration. The consequences of disturbed interorganellar communication are intimately linked with age-related pathologies. Given that both aging and neurodegenerative diseases are characterized by the concomitant failure of multiple cellular pathways, coordination of organelle communication and function could represent an emerging regulatory mechanism critical for long-term cellular homeostasis. We anticipate that defining the relationships between interorganelle communication, aging, and neurodegeneration will open new avenues for therapeutics.

Ventilator Weaning and Terminal Extubation: Withdrawal of Life-Sustaining Therapy in Children. Secondary Analysis of the Death One Hour After Terminal Extubation Study.

OBJECTIVE: Terminal extubation (TE) and terminal weaning (TW) during withdrawal of life-sustaining therapies (WLSTs) have been described and defined in adults. The recent Death One Hour After Terminal Extubation study aimed to validate a model developed to predict whether a child would die within 1 hour after discontinuation of mechanical ventilation for WLST. Although TW has not been described in children, pre-extubation weaning has been known to occur before WLST, though to what extent is unknown. In this preplanned secondary analysis, we aim to describe/define TE and pre-extubation weaning (PW) in children and compare characteristics of patients who had ventilatory support decreased before WLST with those who did not. DESIGN: Secondary analysis of multicenter retrospective cohort study. SETTING: Ten PICUs in the United States between 2009 and 2021. PATIENTS: Nine hundred thirteen patients 0-21 years old who died after WLST. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 71.4% ( n = 652) had TE without decrease in ventilatory support in the 6 hours prior. TE without decrease in ventilatory support in the 6 hours prior = 71.4% ( n = 652) of our sample. Clinically relevant decrease in ventilatory support before WLST = 11% ( n = 100), and 17.6% ( n = 161) had likely incidental decrease in ventilatory support before WLST. Relevant ventilator parameters decreased were F io2 and/or ventilator set rates. There were no significant differences in any of the other evaluated patient characteristics between groups (weight, body mass index, unit type, primary diagnostic category, presence of coma, time to death after WLST, analgosedative requirements, postextubation respiratory support modality). CONCLUSIONS: Decreasing ventilatory support before WLST with extubation in children does occur. This practice was not associated with significant differences in palliative analgosedation doses or time to death after extubation.

Association of diastolic blood pressure with coronary perfusion pressure during resuscitation in pediatric swine.

BACKGROUND: Diastolic blood pressure (DBP) is suggested as a surrogate for coronary perfusion pressure (CPP) during cardiopulmonary resuscitation. We examined the correlation between DBP and CPP and hypothesized that both would be associated with survival in a pediatric swine model of asphyxial cardiac arrest. METHODS: We performed a retrospective, secondary analysis of 102 pediatric swine resuscitations. DBP and CPP were recorded every 30 s during resuscitation. Values were compared between survivors and non-survivors. RESULTS: DBP mirrored CPP in survivors and non-survivors throughout resuscitation and both were associated with survival. Improvements in DBP and CPP after the first epinephrine administration were greater in survivors (DBP: 25.1 ± 3.0 vs. 5.4 ± 0.8 mmHg, p < 0.01; CPP: 24.9 ± 3.2 vs. 4.8 ± 0.9 mmHg, p < 0.01). DBP and CPP after epinephrine administration were highly predictive of survival, with an area under the curve of 0.95 (0.89-1.00) for DBP and 0.90 (0.81-0.99) for CPP. The optimal threshold for DBP was 22.5 mmHg, whereas that for CPP was 14.5 mmHg. CONCLUSIONS: DBP and CPP were associated with survival throughout resuscitation, and the response of both to the first epinephrine administration was highly predictive of survival in this model. Clinically, the availability of DBP makes it useful as a target for physiologic feedback during resuscitation. IMPACT: Diastolic blood pressure (DBP) mirrored coronary perfusion pressure (CPP) throughout prolonged resuscitation in a pediatric model of asphyxial cardiac arrest. Mean DBP and CPP were significantly greater in survivors than in non-survivors both before and after administration of epinephrine. The response of both DBP and CPP to the first dose of epinephrine was highly predictive of return of spontaneous circulation. Given the clinical availability of DBP, these findings support its use as a surrogate for CPP to guide high-quality cardiopulmonary resuscitation in this pediatric swine model.

Community pharmacists' attitudes toward and practice of pharmacy-based harm reduction services in Pittsburgh, PA: a descriptive survey.

BACKGROUND: In Pittsburgh, PA, legal changes in recent decades have set the stage for an expanded role for community pharmacists to provide harm reduction services, including distributing naloxone and non-prescription syringes (NPS). In the wake of the syndemics of the COVID-19 pandemic and worsening overdose deaths from synthetic opioids, we examine knowledge, attitudes, and practices of harm reduction services among community pharmacists in Pittsburgh and identify potential barriers of expanded pharmacy-based harm reduction services. METHODS: We provided flyers to 83 community pharmacies within a 5-mile radius of the University of Pittsburgh Medical Center to recruit practicing community pharmacists to participate in an anonymous electronic survey. We used a 53-question Qualtrics survey consisting of multiple-choice, 5 or 6 point-Likert scale, and open-ended questions adapted from 5 existing survey instruments. Survey measures included demographics, knowledge, attitudes, and practices of harm reduction services (specifically naloxone and NPS provision), and explored self-reported barriers to future implementation. Data was collected July-August 2022. We conducted descriptive analysis using frequencies and proportions reported for categorical variables as well as means and standard deviations (SD) for continuous variables. We analyzed open-ended responses using inductive content analysis. RESULTS: Eighty-eight community pharmacists responded to the survey. 90% of participants agreed pharmacists had a role in overdose prevention efforts, and 92% of participants had previously distributed naloxone. Although no pharmacists reported ever refusing to distribute naloxone, only 29% always provided overdose prevention counseling with each naloxone distributed. In contrast, while 87% of participants had positive attitudes toward the usefulness of NPS for reducing disease, only 73% of participants ever distributed NPS, and 54% had refused NPS to a customer. Participants endorsed a lack of time and concerns over clientele who used drugs as the most significant barriers to offering more comprehensive harm reduction services. CONCLUSIONS: Our findings highlight that while most community pharmacists have embraced naloxone provision, pharmacy policies and individual pharmacists continue to limit accessibility of NPS. Future expansion efforts for pharmacy-based harm reduction services should not only address the time and labor constraints identified by community pharmacists, but also fear-based policy and stigma toward people who inject drugs and harm reduction more broadly.

Enhanced Lyn Activity Causes Severe, Progressive Emphysema and Lung Cancer.

The epidemiological patterns of incident chronic obstructive pulmonary disease (COPD) and lung adenocarcinoma are changing, with an increasing fraction of disease occurring in patients who are never-smokers or were not exposed to traditional risk factors. However, causative mechanism(s) are obscure. Overactivity of Src family kinases (SFKs) and myeloid cell-dependent inflammatory lung epithelial and endothelial damage are independent candidate mechanisms, but their pathogenic convergence has not been demonstrated. Here we present a novel preclinical model in which an activating mutation in Lyn, a nonreceptor SFK that is expressed in immune cells, epithelium, and endothelium-all strongly implicated in the pathogenesis of COPD-causes spontaneous inflammation, early-onset progressive emphysema, and lung adenocarcinoma. Surprisingly, even though activated macrophages, elastolytic enzymes, and proinflammatory cytokines were prominent, bone marrow chimeras formally demonstrated that myeloid cells were not disease initiators. Rather, lung disease arose from aberrant epithelial cell proliferation and differentiation, microvascular lesions within an activated endothelial microcirculation, and amplified EGFR (epidermal growth factor receptor) expression. In human bioinformatics analyses, LYN expression was increased in patients with COPD and was correlated with increased EGFR expression, a known lung oncogenic pathway, and LYN was linked to COPD. Our study shows that a singular molecular defect causes a spontaneous COPD-like immunopathology and lung adenocarcinoma. Furthermore, we identify Lyn and, by implication, its associated signaling pathways as new therapeutic targets for COPD and cancer. Moreover, our work may inform the development of molecular risk screening and intervention methods for disease susceptibility, progression, and prevention of these increasingly prevalent conditions.

Outcomes of the "BRCA Quality Improvement Dissemination Program": An initiative to improve patient receipt of cancer genetics services at five health systems.

OBJECTIVE: A quality improvement initiative (QII) was conducted with five community-based health systems' oncology care centers (sites A-E). The QII aimed to increase referrals, genetic counseling (GC), and germline genetic testing (GT) for patients with ovarian cancer (OC) and triple-negative breast cancer (TNBC). METHODS: QII activities occurred at sites over several years, all concluding by December 2020. Medical records of patients with OC and TNBC were reviewed, and rates of referral, GC, and GT of patients diagnosed during the 2 years before the QII were compared to those diagnosed during the QII. Outcomes were analyzed using descriptive statistics, two-sample t-test, chi-squared/Fisher's exact test, and logistic regression. RESULTS: For patients with OC, improvement was observed in the rate of referral (from 70% to 79%), GC (from 44% to 61%), GT (from 54% to 62%) and decreased time from diagnosis to GC and GT. For patients with TNBC, increased rates of referral (from 90% to 92%), GC (from 68% to 72%) and GT (81% to 86%) were observed. Effective interventions streamlined GC scheduling and standardized referral processes. CONCLUSION: A multi-year QII increased patient referral and uptake of recommended genetics services across five unique community-based oncology care settings.

Development and use of an infant resuscitation performance tool (Infa-RePT) to improve team performance.

BACKGROUND: Measurement of neonatal team resuscitation performance is critical to identify opportunities for improvement and to target education. An effective tool to measure team performance during infant resuscitations is lacking. METHODS: We developed an in-hospital infant resuscitation performance tool (Infa-RePT) using the modified Delphi method. We employed a QI framework and targeted interventions, including the use of role responsibility checklists, mock codes, and an educational video. We tracked Infa-RePT scores, mock code team attendance, and confidence surveys. Our specific aim was to improve Infa-RePT score from a baseline of 7.4 to <5 (lower is better) over a 26-month period. RESULTS: Twenty-five elements reached >80% consensus as essential components to include on the Infa-RePT. Independent observation showed 86% concordance on checklist items. Simulation (n = 26) and unit-based code (n = 10) Infa-RePT scores showed significant improvement after project start from 7.4 to 4.2 (p < 0.01) with special cause variation noted on control chart analysis. No significant difference was observed between simulations and in-unit codes. Staff confidence self-reports improved over the study period. CONCLUSIONS: Use of a novel scoring tool can help monitor team progress over time and identify areas for improvement. Focused interventions can improve resuscitation team performance. IMPACT: We developed and used a novel, comprehensive measurement tool for team infant resuscitation performance in both simulation and in-unit settings. Using QI methodology, team performance improved after the enhancement of a mock code simulation program. Review of team performance scores can highlight key areas to target interventions and monitor progress over time.

Improved detection of flaviviruses in Australian mosquito populations via replicative intermediates.

Mosquito-borne flaviviruses are significant contributors to the arboviral disease burdens both in Australia and globally. While routine arbovirus surveillance remains a vital exercise to identify known flaviviruses in mosquito populations, novel or divergent and emerging species can be missed by these traditional methods. The MAVRIC (monoclonal antibodies to viral RNA intermediates in cells) system is an ELISA-based method for broad-spectrum isolation of positive-sense and double-stranded RNA (dsRNA) viruses based on detection of dsRNA in infected cells. While the MAVRIC ELISA has successfully been used to detect known and novel flaviviruses in Australian mosquitoes, we previously reported that dsRNA could not be detected in dengue virus-infected cells using this method. In this study we identified additional flaviviruses which evade detection of dsRNA by the MAVRIC ELISA. Utilising chimeric flaviviruses we demonstrated that this outcome may be dictated by the non-structural proteins and/or untranslated regions of the flaviviral genome. In addition, we report a modified fixation method that enables improved detection of flavivirus dsRNA and inactivation of non-enveloped viruses from mosquito populations using the MAVRIC system. This study demonstrates the utility of anti-dsRNA monoclonal antibodies for identifying viral replication in insect and vertebrate cell systems and highlights a unique characteristic of flavivirus replication.

Novel monoclonal antibodies against Australian strains of negeviruses and insights into virus structure, replication and host -restriction.

We report the isolation of Australian strains of Bustos virus and Ngewotan virus, two insect-specific viruses in the newly identified taxon Negevirus, originally isolated from Southeast Asian mosquitoes. Consistent with the expected insect-specific tropism of negeviruses, these isolates of Ngewotan and Bustos viruses, alongside the Australian negevirus Castlerea virus, replicated exclusively in mosquito cells but not in vertebrate cells, even when their temperature was reduced to 34 °C. Our data confirmed the existence of two structural proteins, putatively one membrane protein forming the majority of the virus particle, and one glycoprotein forming a projection on the apex of the virions. We generated and characterized 71 monoclonal antibodies to both structural proteins of the two viruses, most of which were neutralizing. Overall, these data increase our knowledge of negevirus mechanisms of infection and replication in vitro.

Neurologic effects of short-term treatment with a soluble epoxide hydrolase inhibitor after cardiac arrest in pediatric swine.

BACKGROUND: Cardiac arrest (CA) is the most common cause of acute neurologic insult in children. Many survivors have significant neurocognitive deficits at 1 year of recovery. Epoxyeicosatrienoic acids (EETs) are multifunctional endogenous lipid signaling molecules that are involved in brain pathobiology and may be therapeutically relevant. However, EETs are rapidly metabolized to less active dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH), limiting their bioavailability. We hypothesized that sEH inhibition would improve outcomes after CA in an infant swine model. Male piglets (3-4 kg, 2 weeks old) underwent hypoxic-asphyxic CA. After resuscitation, they were randomized to intravenous treatment with an sEH inhibitor (TPPU, 1 mg/kg; n = 8) or vehicle (10% poly(ethylene glycol); n = 9) administered at 30 min and 24 h after return of spontaneous circulation. Two sham-operated groups received either TPPU (n = 9) or vehicle (n = 8). Neurons were counted in hematoxylin- and eosin-stained sections from putamen and motor cortex in 4-day survivors. RESULTS: Piglets in the CA + vehicle groups had fewer neurons than sham animals in both putamen and motor cortex. However, the number of neurons after CA did not differ between vehicle- and TPPU-treated groups in either anatomic area. Further, 20% of putamen neurons in the Sham + TPPU group had abnormal morphology, with cell body attrition and nuclear condensation. TPPU treatment also did not reduce neurologic deficits. CONCLUSION: Treatment with an sEH inhibitor at 30 min and 24 h after resuscitation from asphyxic CA does not protect neurons or improve acute neurologic outcomes in piglets.

The use of pressure-controlled mechanical ventilation in a swine model of intraoperative pediatric cardiac arrest.

BACKGROUND: Current pediatric resuscitation guidelines suggest that resuscitators using an advanced airway deliver 8-10 breaths per minute while carefully avoiding excessive ventilation. In the intraoperative setting, having a dedicated ventilation rescuer may be difficult because of limited personnel. Continuing pressure-controlled mechanical ventilation during resuscitation for intraoperative cardiac arrest reduces personnel needed and the risk of hyperventilation but might risk hypoventilation during chest compression delivery. AIMS: To determine whether the use of pressure-controlled mechanical ventilation at prearrest settings provides normoxia and normocarbia during resuscitation from cardiac arrest. METHODS: We retrospectively analyzed combined data from preclinical randomized controlled trials. Two-week-old swine (3-4 kg) underwent asphyxia-induced cardiac arrest. Animals were resuscitated with periods of basic and advanced life support. During resuscitation, pressure-controlled mechanical ventilation was delivered at the prearrest respiratory rate, peak inspiratory pressure, and positive end-expiratory pressure. Arterial blood gases were measured prearrest, at 11 minutes of asphyxia, and at 8 and 20 minutes of cardiopulmonary resuscitation. RESULTS: Piglets (n = 154) received pressure-controlled mechanical ventilation before and during cardiopulmonary resuscitation with a peak inspiratory pressure of 14-15 cm H2 O, positive end-expiratory pressure of 4 cm H2 O, 20 breaths/minute, and an inspiratory:expiratory ratio of 1:2. During asphyxia, the arterial blood gas showed the expected severe hypercarbia and hypoxia. Continuing pressure-controlled mechanical ventilation using prearrest parameters and increasing the FiO2 to 1.0 returned the PaCO2 to prearrest levels and slightly increased the partial pressure of arterial oxygen at 8 and 20 minutes of cardiopulmonary resuscitation. CONCLUSION: In this piglet model of resuscitation from asphyxial arrest, pressure-controlled mechanical ventilation during cardiopulmonary resuscitation at the prearrest ventilator settings with an FiO2 of 1.0 provides adequate oxygenation and restores normocarbia. Clinical investigation is warranted to determine the benefits of continuing pressure-controlled mechanical ventilation at prearrest parameters during pediatric cardiopulmonary resuscitation.

Hypoxia-Ischemia and Hypothermia Independently and Interactively Affect Neuronal Pathology in Neonatal Piglets with Short-Term Recovery.

Therapeutic hypothermia is the standard of clinical care for moderate neonatal hypoxic-ischemic encephalopathy. We investigated the independent and interactive effects of hypoxia-ischemia (HI) and temperature on neuronal survival and injury in basal ganglia and cerebral cortex in neonatal piglets. Male piglets were randomized to receive HI injury or sham procedure followed by 29 h of normothermia, sustained hypothermia induced at 2 h, or hypothermia with rewarming during fentanyl-nitrous oxide anesthesia. Viable and injured neurons and apoptotic profiles were counted in the anterior putamen, posterior putamen, and motor cortex at 29 h after HI injury or sham procedure. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) identified genomic DNA fragmentation to confirm cell death. Though hypothermia after HI preserved viable neurons in the anterior and posterior putamen, hypothermia prevented neuronal injury in only the anterior putamen. Hypothermia initiated 2 h after injury did not protect against apoptotic cell death in either the putamen or motor cortex, and rewarming from hypothermia was associated with increased apoptosis in the motor cortex. In non-HI shams, sustained hypothermia during anesthesia was associated with neuronal injury and corresponding viable neuron loss in the anterior putamen and motor cortex. TUNEL confirmed increased neurodegeneration in the putamen of hypothermic shams. Anesthetized, normothermic shams did not show abnormal neuronal cytopathology in the putamen or motor cortex, thereby demonstrating minimal contribution of the anesthetic regimen to neuronal injury during normothermia. We conclude that the efficacy of hypothermic protection after HI is region specific and that hypothermia during anesthesia in the absence of HI may be associated with neuronal injury in the developing brain. Studies examining the potential interactions between hypothermia and anesthesia, as well as with longer durations of hypothermia, are needed.

Volume-localized measurement of oxygen extraction fraction in the brain using MRI.

PURPOSE: T2 -relaxation-under-spin-tagging (TRUST) is an MR technique for the non-invasive assessment of whole-brain cerebral oxygen extraction fraction (OEF), through measurement of the venous blood T2 relaxation time in the sagittal sinus. A key limitation of TRUST, however, is the lack of spatial specificity of the measurement. We sought to develop a modified TRUST sequence, selective localized TRUST (SL-TRUST), having sensitivity to venous blood T2 within a targeted brain region, and therefore achieving spatially localized measurements of cerebral tissue OEF, while still retaining acquisition in the sagittal sinus. METHODS: A method for selective localization of TRUST sequence was developed, and the reproducibility of the technique was evaluated in healthy participants. Regional measurements were achieved for a single hemisphere and for a 3D-localized 70 × 70 × 80 mm3 tissue region using SL-TRUST and compared to a global TRUST measure. An additional measure of venous blood T1 in the sagittal sinus was used to estimate subject-specific hematocrit. Six subjects were scanned over 4 sessions, including intra-session repeat measurements. RESULTS: The average T2 in the sagittal sinus was found to be 60.8 ± 8.9, 62.7 ± 7.9, 64.6 ± 8.4, and 66.3 ± 10.3 ms (mean ± SD) for conventional TRUST, global SL-TRUST, hemispheric SL-TRUST, and 3D-localized SL-TRUST, respectively. Intra-, inter-session, and inter-subject coefficients of variation for OEF using SL-TRUST were found to be comparable and in some cases superior to those obtained using TRUST. CONCLUSION: OEF comparison of 2 contralateral regions was achievable in under 5 min suggesting SL-TRUST offers potential for quantifying regional OEF differences in both healthy and clinical populations.

The Effect of Asphyxia Arrest Duration on a Pediatric End-Tidal CO2-Guided Chest Compression Delivery Model.

OBJECTIVES: To determine the effect of the duration of asphyxial arrest on the survival benefit previously seen with end-tidal CO2-guided chest compression delivery. DESIGN: Preclinical randomized controlled study. SETTING: University animal research laboratory. SUBJECTS: Two-week-old swine. INTERVENTIONS: After either 17 or 23 minutes of asphyxial arrest, animals were randomized to standard cardiopulmonary resuscitation or end-tidal CO2-guided chest compression delivery. Standard cardiopulmonary resuscitation was optimized by marker, monitor, and verbal feedback about compression rate, depth, and release. End-tidal CO2-guided delivery used adjustments to chest compression rate and depth to maximize end-tidal CO2 level without other feedback. Cardiopulmonary resuscitation for both groups proceeded from 10 minutes of basic life support to 10 minutes of advanced life support or return of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS: After 17 minutes of asphyxial arrest, mean end-tidal CO2 during 10 minutes of cardiopulmonary resuscitation was 18 ± 9 torr in the standard group and 33 ± 15 torr in the end-tidal CO2 group (p = 0.004). The rate of return of spontaneous circulation was three of 14 (21%) in the standard group rate and nine of 14 (64%) in the end-tidal CO2 group (p = 0.05). After a 23-minute asphyxial arrest, neither end-tidal CO2 values (20 vs 26) nor return of spontaneous circulation rate (3/14 vs 1/14) differed between the standard and end-tidal CO2-guided groups. CONCLUSIONS: Our previously observed survival benefit of end-tidal CO2-guided chest compression delivery after 20 minutes of asphyxial arrest was confirmed after 17 minutes of asphyxial arrest. The poor survival after 23 minutes of asphyxia shows that the benefit of end-tidal CO2-guided chest compression delivery is limited by severe asphyxia duration.

A Community's Response to Adverse Childhood Experiences: Building a Resilient, Trauma-Informed Community.

Adverse childhood experiences, or ACEs, may be mitigated by trauma-informed social environments-programs, services, systems, communities-that offer responses to trauma that promote healing, recovery, and resilience. However, there is currently little empirical evidence to support the use of specific approaches to do so. Guided by a population health perspective, this paper describes a participatory community change process in response to ACEs that seeks to build a resilient, trauma-informed community in Pottstown, PA. We examine the initial implementation phase of this change process, centered originally on the education sector and the social and behavioral health services sector, and then eventually expanding to 14 community sectors across two years. A variety of data sources and methods are used to track individual and organizational processes, as well as service system network processes. A central feature of this research is the use of data to generate hypotheses rather than test them. Data were also used to guide understanding and decision-making during implementation. The results show that moving forward the community is well-positioned to establish stronger inter-agency and system supports for trauma-informed practice in the service system and in the broader community. We discuss results for their implications for building resilient, trauma-informed communities.

New genotypes of Liao ning virus (LNV) in Australia exhibit an insect-specific phenotype.

Liao ning virus (LNV) was first isolated in 1996 from mosquitoes in China, and has been shown to replicate in selected mammalian cell lines and to cause lethal haemorrhagic disease in experimentally infected mice. The first detection of LNV in Australia was by deep sequencing of mosquito homogenates. We subsequently isolated LNV from mosquitoes of four genera (Culex, Anopheles, Mansonia and Aedes) in New South Wales, Northern Territory, Queensland and Western Australia; the earliest of these Australian isolates were obtained from mosquitoes collected in 1988, predating the first Chinese isolates. Genetic analysis revealed that the Australian LNV isolates formed two new genotypes: one including isolates from eastern and northern Australia, and the second comprising isolates from the south-western corner of the continent. In contrast to findings reported for the Chinese LNV isolates, the Australian LNV isolates did not replicate in vertebrate cells in vitro or in vivo, or produce signs of disease in wild-type or immunodeficient mice. A panel of human and animal sera collected from regions where the virus was found in high prevalence also showed no evidence of LNV-specific antibodies. Furthermore, high rates of virus detection in progeny reared from infected adult female mosquitoes, coupled with visualization of the virus within the ovarian follicles by immunohistochemistry, suggest that LNV is transmitted transovarially. Thus, despite relatively minor genomic differences between Chinese and Australian LNV strains, the latter display a characteristic insect-specific phenotype.

Discovery of a novel iflavirus sequence in the eastern paralysis tick Ixodes holocyclus.

Ixodes holocyclus, the eastern paralysis tick, is a significant parasite in Australia in terms of animal and human health. However, very little is known about its virome. In this study, next-generation sequencing of I. holocyclus salivary glands yielded a full-length genome sequence which phylogenetically groups with viruses classified in the Iflaviridae family and shares 45% amino acid similarity with its closest relative Bole hyalomma asiaticum virus 1. The sequence of this virus, provisionally named Ixodes holocyclus iflavirus (IhIV) has been identified in tick populations from northern New South Wales and Queensland, Australia and represents the first virus sequence reported from I. holocyclus.

Non-rheumatic streptococcal myocarditis mimicking acute myocardial infarction in an adolescent male.

An adolescent male with a recent history of streptococcal pharyngitis presented with severe substernal chest pain, troponin leak, and ST-segment elevation, which are suggestive of acute inferolateral myocardial infarction. The coronary angiogram was normal. The patient was subsequently diagnosed with non-rheumatic streptococcal myocarditis. He was treated with amoxicillin and had excellent recovery. Non-rheumatic streptococcal myocarditis is an important mimic of acute myocardial infarction in young adults.

Residual Byproducts of Peroxide Crosslinked Vitamin E-Blended Ultrahigh Molecular Weight Polyethylene.

BACKGROUND: Wear resistance of ultrahigh molecular weight polyethylene (UHMWPE) is improved via ionizing radiation crosslinking and subsequent high temperature melting for improved toughness. Our group has previously reported that crosslinking can also be achieved chemically using organic peroxides. However, volatile peroxide byproducts are generated during consolidation. The purpose of this study was to quantify elution of volatile peroxide byproducts from UHMWPE before and after in vivo implantation, and to determine their effects on local tissues. METHODS: We prepared crosslinked UHMWPE samples with 5 times the nominal concentration of peroxide needed for improved wear resistance. Control samples (not crosslinked), crosslinked samples, and crosslinked high temperature melting samples were implanted subcutaneously in New Zealand white rabbits for 28 days. Fourier-transform infrared spectroscopy (FTIR) was used to quantify elution of residual peroxide byproducts, and biocompatibility was determined via histological analysis of periprosthetic tissues. RESULTS: Fourier-transform infrared spectroscopy demonstrated elution of residual peroxide byproducts in vivo. No histological differences were observed between tissues in contact with any of the 3 groups of implants; tissues were characterized by fibrosis and a synovial-like lining for all groups. CONCLUSION: UHMWPE chemically crosslinked with very high concentration of organic peroxide did not show any detrimental changes to surrounding subcutaneous tissues, further demonstrating feasibility of crosslinking UHMWPE with a peroxide, rather than irradiation, for the potential use of the material as a bearing surface for joint arthroplasty.