Early Experiences of Threat,but Not Deprivation,Are Associated With Accelerated Biological Aging in Children and Adolescents

Background

Recent conceptual models argue that early life adversity (ELA) accelerates development, which may contribute to poor mental and physical health outcomes. Evidence for accelerated development in youths comes from studies of telomere shortening or advanced pubertal development following circumscribed ELA experiences and neuroimaging studies of circuits involved in emotional processing. It is unclear whether all ELA is associated with accelerated development across global metrics of biological aging or whether this pattern emerges following specific adversity types.

GeneYenta: A Phenotype­Based Rare Disease Case Matching Tool Based on Online Dating Algorithms for the Acceleration of Exome Interpretation

Advances in next‐generation sequencing (NGS) technologies have helped reveal causal variants for genetic diseases. In order to establish causality, it is often necessary to compare genomes of unrelated individuals with similar disease phenotypes to identify common disrupted genes. When working with cases of rare genetic disorders, finding similar individuals can be extremely difficult. We introduce a web tool, GeneYenta, which facilitates the matchmaking process, allowing clinicians to coordinate detailed comparisons for phenotypically similar cases. Importantly, the system is focused on phenotype annotation, with explicit limitations on highly confidential data that create barriers to participation. The procedure for matching of patient phenotypes, inspired by online dating services, uses an ontology­based semantic case matching algorithm with attribute weighting. We evaluate the capacity of the system using a curated reference data set and 19 clinician entered cases comparing four matching algorithms. We find that the inclusion of clinician weights can augment phenotype matching.     

Reducing postoperative pain by changing the process

Untreated postoperative pain is an important ethical and financial issue that can lead to unnecessary suffering and prolonged stays in hospital. Despite the availability of effective analgesics and a growing body of published material that supports their use, postoperative pain remains a problem worldwide. To reduce acute postoperative pain, we introduced an intervention combining evidence-based analgesic protocols with the education of staff and patients on a surgical ward. The experiences of 68 patients before and 80 patients after the intervention were compared (worst pain scores, duration of pain, and satisfaction). Inadequately controlled pain was significantly reduced after the intervention, which suggests that the introduction of analgesic protocols supported by the education of staff and patients can be beneficial. Despite this, severe pain remained relatively common, indicating room for improvement. Duration of pain and patient satisfaction were not affected by the intervention, and patient satisfaction remained high throughout the study.     

Eye tracking of attention in the affective disorders: A meta-analytic review and synthesis

A large body of research has demonstrated that affective disorders are characterized by attentional biases for emotional stimuli. However, this research relies heavily on manual reaction time (RT) measures that cannot fully delineate the time course and components of attentional bias. Eye tracking technology, which allows relatively direct and continuous measurement of overt visual attention, may provide an important supplement to RT measures. This article reviews eye tracking research on anxiety and depression, evaluating the experimental paradigms and eye movement indicators used to study attentional biases. Also included is a meta-analysis of extant eye tracking research (33 experiments; N = 1579) on both anxiety and depression. Relative to controls, anxious individuals showed increased vigilance for threat during free viewing and visual search, and showed difficulty disengaging from threat in visual search tasks, but not during free viewing. In contrast, depressed individuals were not characterized by vigilance for threat during free viewing, but were characterized by reduced orienting to positive stimuli, as well as reduced maintenance of gaze on positive stimuli and increased maintenance of gaze on dysphoric stimuli. Implications of these findings for theoretical accounts of attentional bias in anxiety and depression are discussed, and avenues for future research using eye-tracking technology are outlined.     

Osteoporotic Vertebral Fractures are Common in Hip Fracture Patients and are Under-recognized

Introduction: The vertebrae are the most common site for osteoporotic fracture. While they can result in disability and increased mortality, only one-third present clinically. People with multiple fractures are at greater risk of future fractures. Most hip fracture patients are neither diagnosed nor treated for their underlying osteoporosis. Computed tomography (CT) studies are often performed on hospitalised patients, can be used to diagnose osteoporosis and are gaining popularity for opportunistic osteoporosis screening by measuring BMD and other bone strength indices. The aim of this study was to assess the prevalence of vertebral fractures on CT pulmonary angiograms (CTPA) in a cohort of hip fracture patients and whether this increased their diagnosis and treatment rates. Methods: We retrospectively identified all hip fractures admitted to our institution between 2010 and 2017 to identify those who underwent CTPA scans. An independent, blinded consultant musculoskeletal radiologist reviewed the images for vertebral fractures and quantified severity using Genant criteria. Results were compared to the original radiology report, discharge diagnoses and treatment rates for osteoporosis. Results:Eleven percent (225/2122) of patients had CTPA images available. Seventy percent (158) were female with a mean age of 78 years (SD: 11). The median length of stay for all patients was 16 days (1–301). Forty percent (90) of patients had at least one vertebral fracture present and 20% (46) had more than one fracture. Only one in 5 radiology reports noted the fractures. 24% of subjects had osteoporosis treatment recorded at hospital discharge and there was no difference between those with vertebral fractures to those without. Conclusion: Many hip fracture patients have undiagnosed spine fractures. A screening strategy which evaluates CT scans for fractures has potential to increase diagnosis and treatment rates of osteoporosis. However, more work is needed to increase awareness.     

Ultra-Violet Light Emission from HPV-G Cells Irradiated with Low Let Radiation From 90Y; Consequences for Radiation Induced Bystander Effects

In this study, we aimed to establish the emission of UV photons when HPV-G cells and associated materials (such as the cell substrate and cell growth media) are exposed to low LET radiation. The potential role of UV photons in the secondary triggering of biological processes led us to hypothesize that the emission and absorption of photons at this wavelength explain some radiation induced “bystander effects” that have previously been thought to be chemically mediated. Cells were plated in Petri-dishes of two different sizes, having different thicknesses of polystyrene (PS) substrate, and were exposed to β-radiation from ⁹⁰Y produced by the McMaster Nuclear Reactor. UV measurements were performed using a single photon counting system employing an interference-type filter for selection of a narrow wavelength range, 340±5 nm, of photons. Exposure of the cell substrates (which were made of polystyrene) determined that UV photons were being emitted as a consequence of β particle irradiation of the Petri-dishes. For a tightly collimated β-particle beam exposure, we observed 167 photons in the detector per unit μCi in the shielded source for a 1.76 mm thick substrate and 158 photons/μCi for a 0.878 mm thick substrate. A unit μCi source activity was equivalent to an exposure to the substrate of 18 β-particles/cm² in this case. The presence of cells and medium in a Petri-dish was found to significantly increase (up to a maximum of 250%) the measured number of photons in a narrow band of wavelengths of 340±5 nm (i.e. UVA) as compared to the signal from an empty control Petri-dish. When coloured growth medium was added to the cells, it reduced the measured count rate, while the addition of transparent medium in equal volume increased the count rate, compared to cells alone. We attribute this to the fact that emission, scattering and absorption of light by cells and media are all variables in the experiment. Under collimated irradiation conditions, it was observed that increasing cell density in medium of fixed volume resulted in a decrease in the observed light output. This followed a roughly exponential decline. We suggest that this may be due to increased scattering at the cell boundary and absorption of the UV in the cells. We conclude that we have measured UVA emitted by cells, cell medium and cell substrates as a consequence of their irradiation by low LET β-particle radiation. We suggest that these secondary UV photons could lead to effects in non-targetted cells. Some effects that had previously been attributed to a chemically mediated “bystander effect” may in fact be due to secondary UV emission. Some radiation bystander effect studies may require re-interpretation as this phenomenon of UV emission is further investigated.