Conduction abnormalities are restricted to the central nervous system in experimental autoimmune encephalomyelitis induced by inoculation with proteolipid protein but not with myelin basic protein

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system (CNS) and can be induced by inoculation of animals with homogenized CNS tissue or highly purified myelin proteins such as myelin basic protein (MBP) or proteolipid protein (PLP). It is widely studied as a possible animal model of multiple sclerosis. We performed the present neurophysiological study to define the location of nerve conduction abnormalities in EAE induced by immunization with PLP (PLP-EAE) and in EAE induced by immunization with MBP (MBP-EAE) in the Lewis rat. In rats with tail weakness due to acute PLP-EAE, conduction was normal in the spinal nerve roots and peripheral nerves but there was evidence of conduction block in a high proportion of the fibres in the dorsal columns of the lumbosacral spinal cord. In contrast, in acute MBP-EAE, there was conduction block in a high proportion of fibres in the sacral dorsal and ventral roots of the peripheral nervous system (PNS) and in the dorsal columns of the lumbosacral spinal cord. The distribution of nerve conduction abnormalities is consistent with previous histological studies showing that inflammation and primary demyelination are restricted to the CNS in PLP-EAE, but are present in the CNS and in the spinal roots of the PNS in MBP-EAE. The restriction of functional abnormalities to the CNS in PLP-EAE but not in MBP-EAE may have implications for the human inflammatory demyelinating diseases, including multiple sclerosis

An innovative resuscitation training strategy for primary care nurses: feasibility study for a randomised controlled trial

Unexpected cardiac arrest remains a significant cause of out-of-hospital death world-wide, and prompt recognition of cardiac arrest and initiation of resuscitation is the predominating factor in quadrupling survival from out-of-hospital cardiac arrest. Patients with more complex needs are being cared for in primary care, yet primary care nurses lack access to a dedicated cardiac arrest team. An annual resuscitation training interval is frequently recommended, but the optimum resuscitation training interval is not known. Globally, resuscitation knowledge and skill retention is notoriously poor, and skills decay takes place well before the commonly adopted 12 month re-training interval.The primary aims were to develop and refine a new intervention with involvement of relevant stakeholders, determining the feasibility and acceptability of proposed study procedures and outcome measures. The secondary aim was to determine whether useful data were likely to result from the main study. The intended outcome was that the following post-doctoral, statistically-powered, full-scale randomised controlled trial to assess the effect of the new resuscitation training intervention will deliver maximum benefit. The development of a cost-effective, optimal model of resuscitation training should provide the best care for patients, resulting in more lives being saved. A stakeholder meeting gained consensus on the design of the strategy, content, delivery method and frequency of training, consistent with current Resuscitation Council UK guidelines. Consensus from the stakeholder meeting was the addition of the Lifesaver app as the intervention. A mixed methods design was adopted. Participants engaged in a scenario using a manikin and a scenario from the Lifesaver app to demonstrate resuscitation including defibrillation skills. Quantitative data were collected using the Lifesaver app, scenario observations sheets, QCPR app and questionnaires. Narrative data were elicited at each visit from a short, in-person focused interview. The study was conducted at a variety of NHS sites.Sampling worked well. Additional primary care roles were included during recruitment due to demand and feedback from participants. All data collection modes were effective and resulted in robust data. Minor changes were highlighted for the main study: removing ambiguity from the true/false questionnaire and improving the layout of the this and the observation sheet for easier completion. Participants were positive about the interactive app as the intervention. Debriefing was essential, and participants valued repeated practice as unconscious competence was revealed. Resuscitation knowledge and skills were maintained over time. Modifications to the study necessitated by the COVID-19 pandemic allowed the study to continue. This will inform essential training during future pandemics.The procedures used in this study were deemed to be feasible and acceptable, such that the main study can proceed. Application of the intervention at three-monthly intervals promoted maintenance of resuscitation knowledge and skills over time. This suggests sufficient justification to proceed to the main intervention study

Insensitivity of alkenone carbon isotopes to atmospheric CO₂ at low to moderate CO₂ levels

Atmospheric pCO2 is a critical component of the global carbon system and is considered to be the major control of Earth’s past, present and future climate. Accurate and precise reconstructions of its concentration through geological time are, therefore, crucial to our understanding of the Earth system. Ice core records document pCO2 for the past 800 kyrs, but at no point during this interval were CO2 levels higher than today. Interpretation of older pCO2 has been hampered by discrepancies during some time intervals between two of the main ocean-based proxy methods used to reconstruct pCO2: the carbon isotope fractionation that occurs during photosynthesis as recorded by haptophyte biomarkers (alkenones) and the boron isotope composition (δ11B) of foraminifer shells. Here we present alkenone and δ11B-based pCO2 reconstructions generated from the same samples from the Plio-Pleistocene at ODP Site 999 across a glacial-interglacial cycle. We find a muted response to pCO2 in the alkenone record compared to contemporaneous ice core and δ11B records, suggesting caution in the interpretation of alkenone-based records at low pCO2 levels. This is possibly caused by the physiology of CO2 uptake in the haptophytes. Our new understanding resolves some of the inconsistencies between the proxies and highlights that caution may be required when interpreting alkenone-based reconstructions of pCO2

The isotopic composition (d15N, d13C) of agricultural wastes and derived composts.

The aim of this study was to measure variations in the isotopic composition (d13C and d15N) during the composting of different agricultural wastes using bench-scale bioreactors. Four different feedstocks of agricultural wastes (Horse bedding manure + legumes residues; Dairy manure + Jatropha mill cake; Dairy manure + sugarcane residues; Dairy manure) were used for aerobic-thermophilic composting. During composting no significant differences were found between the d13C values of the source material and the compost, except for Dairy manure + sugarcane residues. d15N values increased significantly in composts of Horse bedding manure + legumes residues and Dairy manure + Jatropha mill cake. d15N values of composts may be related to NH3 volatilization during the composting process. Isotopic signatures (d13C, d15N) can be used to differentiate composts from different feedstock sources and d15N values may be a quantitative indicator of NH3 volatilization during composting. Use of bench-scale bioreactors is a promising apparatus to study the dynamics of C and N and stable isotopes signatures during composting, but future adjustments regarding sampling methodology are necessary

Activation of PTHrP-cAMP-CREB1 signaling following p53 loss is essential for osteosarcoma initiation and maintenance

Mutations in the P53 pathway are a hallmark of human cancer. The identification of pathways upon which p53-deficient cells depend could reveal therapeutic targets that may spare normal cells with intact p53. In contrast to P53 point mutations in other cancer, complete loss of P53 is a frequent event in osteosarcoma (OS), the most common cancer of bone. The consequences of p53 loss for osteoblastic cells and OS development are poorly understood. Here we use murine OS models to demonstrate that elevated Pthlh (Pthrp), cAMP levels and signalling via CREB1 are characteristic of both p53-deficient osteoblasts and OS. Normal osteoblasts survive depletion of both PTHrP and CREB1. In contrast, p53-deficient osteoblasts and OS depend upon continuous activation of this pathway and undergo proliferation arrest and apoptosis in the absence of PTHrP or CREB1. Our results identify the PTHrP-cAMP-CREB1 axis as an attractive pathway for therapeutic inhibition in OS.Mannu K Walia, Patricia MW Ho, Scott Taylor, Alvin JM Ng, Ankita Gupte, Alistair M Chalk, Andrew CW Zannettino, T John Martin, Carl R Walkle

A Systematic Review on the Use of Psychosocial Interventions in Conjunction with Medications for the Treatment of Opioid Addiction

Opioid use and overdose rates have risen to epidemic levels in the United States during the past decade. Fortunately, there are effective medications (ie, methadone, buprenorphine, and oral and injectable naltrexone) available for the treatment of opioid addiction. Each of these medications is approved for use in conjunction with psychosocial treatment; however, there is a dearth of empirical research on the optimal psychosocial interventions to use with these medications. In this systematic review, we outline and discuss the findings of 3 prominent prior reviews and 27 recent publications of empirical studies on this topic. The most widely studied psychosocial interventions examined in conjunction with medications for opioid addiction were contingency management and cognitive behavioral therapy, with the majority focusing on methadone treatment. The results generally support the efficacy of providing psychosocial interventions in combination with medications to treat opioid addictions, although the incremental utility varied across studies, outcomes, medications, and interventions. The review highlights significant gaps in the literature and provides areas for future research. Given the enormity of the current opioid problem in the United States, it is critical to gain a better understanding of the most effective ways to deliver psychosocial treatments in conjunction with these medications to improve the health and well-being of individuals suffering from opioid addiction