Establishment, Immortalisation and Characterisation of Pteropid Bat Cell Lines

BACKGROUND: Bats are the suspected natural reservoir hosts for a number of new and emerging zoonotic viruses including Nipah virus, Hendra virus, severe acute respiratory syndrome coronavirus and Ebola virus. Since the discovery of SARS-like coronaviruses in Chinese horseshoe bats, attempts to isolate a SL-CoV from bats have failed and attempts to isolate other bat-borne viruses in various mammalian cell lines have been similarly unsuccessful. New stable bat cell lines are needed to help with these investigations and as tools to assist in the study of bat immunology and virus-host interactions. METHODOLOGY/FINDINGS: Black flying foxes (Pteropus alecto) were captured from the wild and transported live to the laboratory for primary cell culture preparation using a variety of different methods and culture media. Primary cells were successfully cultured from 20 different organs. Cell immortalisation can occur spontaneously, however we used a retroviral system to immortalise cells via the transfer and stable production of the Simian virus 40 Large T antigen and the human telomerase reverse transcriptase protein. Initial infection experiments with both cloned and uncloned cell lines using Hendra and Nipah viruses demonstrated varying degrees of infection efficiency between the different cell lines, although it was possible to infect cells in all tissue types. CONCLUSIONS/SIGNIFICANCE: The approaches developed and optimised in this study should be applicable to bats of other species. We are in the process of generating further cell lines from a number of different bat species using the methodology established in this study

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Prevalence and impact of depression in cystic fibrosis

Numerous studies have demonstrated that patients with chronic illnesses are at an increased risk for depression, with serious direct and indirect consequences for health outcomes. The few studies examining rates of depression in patients with cystic fibrosis (CF) or parent caregivers have found clinically significant elevations. Given the importance of identifying and treating symptoms of depression, the purpose of this review was to highlight recent data on the prevalence and impact of depression in CF patients and to propose recommendations for screening and treatment. Recent studies in CF have revealed higher rates of depression in children, adolescents, adults, and parent caregivers than in healthy populations. Evidence also suggests that depression has negative effects on treatment adherence, family functioning, and health-related quality of life. Briefly, well validated screening tools for depression are available but are not currently utilized in routine CF care. Effective psychological and pharmacological interventions are available to treat depression, but have not yet been evaluated in patients with CF. Depression is a significant risk factor for the effective management of CF. Screening and treatment of depression in CF centers is recommended and holds promise for improving social, emotional, and physical health outcomes

Challenges of Disorders of Sex Development: Diverse Perceptions across Stakeholders

BACKGROUND/AIMS: Disorders of Sex Development (DSD) are congenital conditions in which chromosomal, gonadal, or anatomic sex development is atypical. Optimal management is patient- and family-centered and delivered by interdisciplinary teams. The present pilot study elicits concerns held by important stakeholders on issues affecting young patients with DSD and their families. METHODS: Content from focus groups with expert clinicians (pediatric urologists [n=7], pediatric endocrinologists [n=10], mental health professionals [n=4]), DSD patient advocates (n=4), and interviews with parents of DSD-affected children (newborn to 6 yrs; n=11) was coded and content-analyzed to identify health-related quality of life issues. RESULTS: Key stressors varied across stakeholder groups. In general, family-centered issues were noted more than child-centered. In the child-centered domain, providers worried more about physical functioning; family and advocates emphasized gender concerns and body image. In the family-centered domain, parental concerns about medication management outweighed those of providers. Advocates reported more stressors regarding communication/information than other stakeholders. CONCLUSION: Variability exists across stakeholder groups in the key concerns affecting young children/families with DSD. Interdisciplinary DSD healthcare team development should account for varying perspectives when counseling families and planning treatment

Parenting Stress Among Parents of Deaf and Hearing Children: Associations with Language Delays and Behavior Problems

Objective. This study evaluates predictors of both general and context-specific parenting stress in a cross-sectional sample of hearing parents of young deaf and hearing children. Design. Participants were 181 children who were deaf and 92 children with normal hearing. Perceived parenting stress was measured using both general and context-specific measures. Predictors of parenting stress included parent-reported and observed child behavior problems and language delays. Results. After control for maternal education and family income, parents of deaf children reported more context-specific but not general parenting stress than parents of hearing children. Both parent-reported and observed behavior problems were higher in the deaf group compared with that in the hearing group. Children's hearing status related to child behavior problems by way of oral language delays. Furthermore, hearing status related to parenting stress by way of language delays and child behavior difficulties. Conclusions. Context-specific measures of parenting stress reflect unique challenges of this population. Both language delays and child behavior problems are associated with increased parenting stress. Identification of specific stressors related to parenting a deaf child helps to inform the development of early interventions

Improvements in visual attention in deaf infants and toddlers after cochlear implantation

The aims of this study were to examine the development of visual attention in deaf and hearing infants and toddlers, and assess whether improvements in visual attention were observed in the deaf sample after 12 months of cochlear implantation. A novel puppet task, based on a measure of attention developed with normally hearing infants, was administered to 88 deaf and 42 normal-hearing children at three time points: baseline, six and 12 months post-implantation for the deaf sample. At baseline, deaf children demonstrated significantly more inattentive looks during the puppet skits than hearing children, and these looks were of longer duration, confirming the results of prior studies which have documented deficits in visual attention in deaf children. Longitudinal analyses showed significant decreases in the frequency of inattentive looks for both groups, with a significant decrease in the duration of inattentive looks only for the cochlear implant group. The largest decrease in duration of off-task looks occurred at six months post-implantation, indicating that improvements occurred rapidly after restoration of auditory input. These results provided support for the 'division of labor' hypothesis which suggests that deaf children with no access or limited access to sound must monitor their environment visually, making it difficult for them to focus and attend to specific tasks. Cochlear implantation appeared to alter the developmental trajectory of visual attention in a positive manner. The clinical implications of visual attention for the development of early language, reading and social skills are discussed

Unrelated donor cord blood transplantation for children with severe sickle cell disease: results of one cohort from the phase II study from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN).

The Sickle Cell Unrelated Donor Transplant Trial (SCURT trial) of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) is a phase II study of the toxicity and efficacy of unrelated donor hematopoietic cell transplantation in children with severe sickle cell disease (SCD) using a reduced-intensity conditioning regimen. Here we report the results for the cord blood cohort of this trial. Eight children with severe SCD underwent unrelated donor cord blood transplantation (CBT) following alemtuzumab, fludarabine, and melphalan. Cyclosporine or tacrolimus and mycophenolate mofetil were administered for graft-versus-host disease (GVHD) prophylaxis. Donor/recipient HLA match status was 6 of 6 (n = 1) or 5 of 6 (n = 7), based on low/intermediate-resolution molecular typing at HLA -A, -B, and high-resolution typing at -DRB1. Median recipient age was 13.7 years (range: 7.4-16.2 years), and median weight was 35.0 kg (range: 25.2-90.2 kg). The median precryopreservation total nucleated cell dose was 6.4 × 107 /kg (range: 3.1-7.6), and the median postthaw infused CD34 cell dose was 1.5 × 105 /kg (range: 0.2-2.3). All patients achieved neutrophil recovery (absolute neutrophil count >500/mm3) by day 33 (median: 22 days). Three patients who engrafted had 100% donor cells by day 100, which was sustained, and 5 patients had autologous hematopoietic recovery. Six of 8 patients had a platelet recovery to >50,000/mm3 by day 100. Two patients developed grade II acute GVHD. Of these, 1 developed extensive chronic GVHD and died of respiratory failure 14 months posttransplantation. With a median follow-up of 1.8 years (range: 1-2.6), 7 patients are alive with a 1-year survival of 100%, and 3 of 8 are alive without graft failure or disease recurrence. Based upon the high incidence of graft rejection after unrelated donor CBT, enrollment onto the cord blood arm of the SCURT trial was suspended. However, because this reduced-intensity regimen has demonstrated a favorable safety profile, this trial remains open to enrollment for unrelated marrow donor transplants. Novel approaches aimed at improving engraftment will be needed before unrelated CBT can be widely adopted for transplanting patients with severe SCD