Role of Optical Neuromonitoring in Neonatal Encephalopathy—Current State and Recent Advances

Neonatal encephalopathy (NE) in term and near-term infants is a significant global health problem; the worldwide burden of disease remains high despite the introduction of therapeutic hypothermia. Assessment of injury severity and effective management in the neonatal intensive care unit (NICU) relies on multiple monitoring modalities from systemic to brain-specific. Current neuromonitoring tools provide information utilized for seizure management, injury stratification, and prognostication, whilst systemic monitoring ensures multi-organ dysfunction is recognized early and supported wherever needed. The neuromonitoring technologies currently used in NE however, have limitations in either their availability during the active treatment window or their reliability to prognosticate and stratify injury confidently in the early period following insult. There is therefore a real need for a neuromonitoring tool that provides cot side, early and continuous monitoring of brain health which can reliably stratify injury severity, monitor response to current and emerging treatments, and prognosticate outcome. The clinical use of near-infrared spectroscopy (NIRS) technology has increased in recent years. Research studies within this population have also increased, alongside the development of both instrumentation and signal processing techniques. Increasing use of commercially available cerebral oximeters in the NICU, and the introduction of advanced optical measurements using broadband NIRS (BNIRS), frequency domain NIRS (FDNIRS), and diffuse correlation spectroscopy (DCS) have widened the scope by allowing the direct monitoring of oxygen metabolism and cerebral blood flow, both key to understanding pathophysiological changes and predicting outcome in NE. This review discusses the role of optical neuromonitoring in NE and why this modality may provide the next significant piece of the puzzle toward understanding the real time state of the injured newborn brain

Anaplastic Lymphoma Kinase Immunocytochemistry on Cell-Transferred Cytologic Smears of Lung Adenocarcinoma

Background: Anaplastic lymphoma kinase (ALK) immunohistochemical staining on formalin-fixed paraffin-embedded tissue or cell blocks (CB) has been reported as an effective alternative to fluorescence hybridization in situ (FISH) for the detection of ALK gene rearrangement. However, CB frequently lack adequate cellularity even when the direct smears are cellular. This study aims to assess the utility of ALK immunocytochemical (ICC) staining on direct smears using the cell transfer (CT) technique for the detection of ALK rearrangement. Methods: Fine-needle aspiration (FNA) cases of lung adenocarcinoma in which the ALK status had been determined by FISH on CB or a concurrent biopsy were identified. ICC staining for ALK was performed on alcohol-fixed Papanicolaou-stained direct smears using the CT technique. ALK immunoreactivity was evaluated using a modified semiquantitative scale. Results were compared with those of FISH. Results: A total of 47 FNA specimens were included. Five of 7 FISH-positive cases showed positive ALK ICC staining (71.4%), and 39 of 40 FISH-negative cases were negative on ALK ICC staining (97.5%). The overall correlation between ALK ICC and FISH was 93.6%. Conclusion: ICC performed on FNA smears using the CT technique is an alternative method for the assessment of ALK rearrangement, especially when CB lack adequate cellularity

Brain temperature monitoring in newborn infants:Current methodologies and prospects

Brain tissue temperature is a dynamic balance between heat generation from metabolism, passive loss of energy to the environment, and thermoregulatory processes such as perfusion. Perinatal brain injuries, particularly neonatal encephalopathy, and seizures, have a significant impact on the metabolic and haemodynamic state of the developing brain, and thereby likely induce changes in brain temperature. In healthy newborn brains, brain temperature is higher than the core temperature. Magnetic resonance spectroscopy (MRS) has been used as a viable, non-invasive tool to measure temperature in the newborn brain with a reported accuracy of up to 0.2 degrees Celcius and a precision of 0.3 degrees Celcius. This measurement is based on the separation of chemical shifts between the temperature-sensitive water peaks and temperature-insensitive singlet metabolite peaks. MRS thermometry requires transport to an MRI scanner and a lengthy single-point measurement. Optical monitoring, using near infrared spectroscopy (NIRS), offers an alternative which overcomes this limitation in its ability to monitor newborn brain tissue temperature continuously at the cot side in real-time. Near infrared spectroscopy uses linear temperature-dependent changes in water absorption spectra in the near infrared range to estimate the tissue temperature. This review focuses on the currently available methodologies and their viability for accurate measurement, the potential benefits of monitoring newborn brain temperature in the neonatal intensive care unit, and the important challenges that still need to be addressed

The Extracellular Vesicle Citrullinome and Signature in a Piglet Model of Neonatal Seizures

Neonatal seizures are commonly associated with acute perinatal brain injury, while understanding regarding the downstream molecular pathways related to seizures remains unclear. Furthermore, effective treatment and reliable biomarkers are still lacking. Post-translational modifications can contribute to changes in protein function, and post-translational citrullination, which is caused by modification of arginine to citrulline via the calcium-mediated activation of the peptidylarginine deiminase (PAD) enzyme family, is being increasingly linked to neurological injury. Extracellular vesicles (EVs) are lipid-bilayer structures released from cells; they can be isolated from most body fluids and act as potential liquid biomarkers for disease conditions and response to treatment. As EVs carry a range of genetic and protein cargo that can be characteristic of pathological processes, the current study assessed modified citrullinated protein cargo in EVs isolated from plasma and CSF in a piglet neonatal seizure model, also following phenobarbitone treatment. Our findings provide novel insights into roles for PAD-mediated changes on EV signatures in neonatal seizures and highlight the potential of plasma- and CSF-EVs to monitor responses to treatment

Is the pharmacy profession innovative enough?: meeting the needs of Australian residents with chronic conditions and their carers using the nominal group technique

Background Community pharmacies are ideally located as a source of support for people with chronic conditions. Yet, we have limited insight into what innovative pharmacy services would support this consumer group to manage their condition/s. The aim of this study was to identify what innovations people with chronic conditions and their carers want from their ideal community pharmacy, and compare with what pharmacists and pharmacy support staff think consumers want. Methods We elicited ideas using the nominal group technique. Participants included people with chronic conditions, unpaid carers, pharmacists and pharmacy support staff, in four regions of Australia. Themes were identified via thematic analysis using the constant comparison method. Results Fifteen consumer/carer, four pharmacist and two pharmacy support staff groups were conducted. Two overarching themes were identified: extended scope of practice for the pharmacist and new or improved pharmacy services. The most innovative role for Australian pharmacists was medication continuance, within a limited time-frame. Consumers and carers wanted improved access to pharmacists, but this did not necessarily align with a faster or automated dispensing service. Other ideas included streamlined access to prescriptions via medication reminders, electronic prescriptions and a chronic illness card. Conclusions This study provides further support for extending the pharmacist’s role in medication continuance, particularly as it represents the consumer’s voice. How this is done, or the methods used, needs to optimise patient safety. A range of innovative strategies were proposed and Australian community pharmacies should advocate for and implement innovative approaches to improve access and ensure continuity of care

The celebrity entrepreneur on television: profile, politics and power

This article examines the rise of the ‘celebrity entrepreneur’ on television through the emergence of the ‘business entertainment format’ and considers the ways in which regular television exposure can be converted into political influence. Within television studies there has been a preoccupation in recent years with how lifestyle and reality formats work to transform ‘ordinary’ people into celebrities. As a result, the contribution of vocationally skilled business professionals to factual entertainment programming has gone almost unnoticed. This article draws on interviews with key media industry professionals and begins by looking at the construction of entrepreneurs as different types of television personalities and how discourses of work, skill and knowledge function in business shows. It then outlines how entrepreneurs can utilize their newly acquired televisual skills to cultivate a wider media profile and secure various forms of political access and influence. Integral to this is the centrality of public relations and media management agencies in shaping media discourses and developing the individual as a ‘brand identity’ that can be used to endorse a range of products or ideas. This has led to policy makers and politicians attempting to mobilize the media profile of celebrity entrepreneurs to reach out and connect with the public on business and enterprise-related issues

The Extracellular Vesicle Citrullinome and Signature in a Piglet Model of Neonatal Seizures

Neonatal seizures are commonly associated with acute perinatal brain injury, while understanding regarding the downstream molecular pathways related to seizures remains unclear. Furthermore, effective treatment and reliable biomarkers are still lacking. Post-translational modifications can contribute to changes in protein function, and post-translational citrullination, which is caused by modification of arginine to citrulline via the calcium-mediated activation of the peptidylarginine deiminase (PAD) enzyme family, is being increasingly linked to neurological injury. Extracellular vesicles (EVs) are lipid-bilayer structures released from cells; they can be isolated from most body fluids and act as potential liquid biomarkers for disease conditions and response to treatment. As EVs carry a range of genetic and protein cargo that can be characteristic of pathological processes, the current study assessed modified citrullinated protein cargo in EVs isolated from plasma and CSF in a piglet neonatal seizure model, also following phenobarbitone treatment. Our findings provide novel insights into roles for PAD-mediated changes on EV signatures in neonatal seizures and highlight the potential of plasma- and CSF-EVs to monitor responses to treatment

Omicron neutralising antibodies after COVID-19 vaccination in haemodialysis patients.

Funder: Kidney Research U