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The RCGP and its Junior International Committee have a long history of supporting early career GPs to undertake observational exchanges to experience international primary care systems first-hand. The benefits of international exchanges are wide-ranging and include allowing participants to develop collaborations, learn more about primary healthcare in the host country, reflect on that learning, and bring it back to their own practice. This article discusses the current opportunities for early career GPs and describes some of the existing evidence regarding the educational, personal and professional benefits, as well as challenges these may bring to participants, patients and the wider health system. [ABSTRACT FROM AUTHOR]

The polyamines (putrescine, spermidine, and spermine) are synthesized by almost all organisms and are universally required for normal growth. Ornithine decarboxylase (ODC), an initial enzyme of polyamine synthesis, is one of the most highly regulated enzymes of eucaryotic organisms. Unusual mechanisms have evolved to control ODC, including rapid, polyamine-mediated turnover of the enzyme and control of the synthetic rate of the protein without change of its mRNA level. The high amplitude of regulation and the rapid variation in the level of the protein led biochemists to infer that polyamines had special cellular roles and that cells maintained polyamine concentrations within narrow limits. This view was sustained in part because of our continuing uncertainty about the actual biochemical roles of polyamines. In this article, we challenge the view that ODC regulation is related to precise adjustment of polyamine levels. In no organism does ODC display allosteric feedback inhibition, and in three types of organism, bacteria, fungi, and mammals, the size of polyamine pools may vary radically without having a profound effect on growth. We suggest that the apparent stability of polyamine pools in unstressed cells is due to their being largely bound to cellular polyanions. We further speculate that allosteric feedback inhibition, if it existed, would be inappropriately responsive to changes in the small, freely diffusible polyamine pool. Instead, mechanisms that control the amount of the ODC protein have appeared in most organisms, and even these are triggered inappropriately by variation of the binding of polyamines to ionic binding sites. In fact, feedback inhibition of ODC might be maladaptive during hypoosmotic stress or at the onset of growth, when organisms appear to require rapid increases in the size of their cellular polyamine pools.

Reviews the web site www.qplmed.org or the Clinician's Guide to the Choice of Instruments for Quality of Life Assessment in Medicine, developed by Marcello Tamburini.

Introduction: We examine ways intraoperative neuromonitoring during spinal cord stimulation (SCS) varies between a high-resolution investigational SCS (HR-SCS) paddle and a commercial paddle. Furthermore, the presence of evoked motor responses (eg, electromyography [EMG]) in painful regions during surgery is correlated to outcomes., Materials and Methods: We used HR-SCS to assess EMG response from 18 patients (NCT05459324). Maximum percentage change in root mean squared (maxRMS) EMG values was determined. Correlations were performed with magnetic resonance imaging measurements and patient outcomes collected preoperatively and at three months (numerical rating scale [NRS], McGill Pain, Beck Depression Inventory, Oswestry Disability Index [ODI], and Pain Catastrophizing Score)., Results: Of the 18 patients (12 women to six men; mean age 56 years; eight with neuropathic pain, eight with persistent spinal pain syndrome, two with complex regional pain syndrome), nine had a response at three months based on 50% reduction in NRS, 14 by achieving minimal clinically important difference (MCID) on NRS, and 11 by reaching MCID on ≥three outcome metrics. The anterior posterior diameter (APD) of the spinal column at level of testing correlated with all three responses (p < 0.05). We examined RMS at muscles correlating with individual patient pain distributions and found correlations between RMS and MCID NRS and MCID ODI (p < 0.05). maxRMS in abductor hallucis correlated with improvement in NRS and ODI across the group (p < 0.05)., Conclusions: We found that eliciting EMGs over the painful areas during surgery caused alleviation of pain intensity and disability. Obtaining stimulation of abductor hallucis (AH) was more predictive of pain improvement than any other muscle group, and APD alone correlated with improvements in pain intensity and holistic outcomes. These pilot data suggest that implanters should consider APD and EMG responses from painful regions and AH during surgery., Competing Interests: Conflict of Interest Julie G. Pilitsis receives grant support from Medtronic, Boston Scientific, Abbott, Focused Ultrasound Foundation, National Institutes of Health (NIH) 2R01CA166379, NIH R01EB030324, and NIH-NeuroBlueprint MedTech 5U54EB033650. She is the medical advisor for Aim Medical Robotics and has stock equity. Ilknur Telkes has grant support from NIH R00NS119672, NIH U44NS115111, and Florida Atlantic University College of Engineering & Computer Science/Institute for Sensing and Embedded Network Systems Engineering (FAU COECS/I-SENSE). Bryan L. McLaughlin has grant support from NIH U44NS115111 and is an employee of Micro-Leads, Inc. Yohannes Iyassu is an employee of Micro-Leads Inc. Steven Paniccioli is an employee of Nuvasive. The remaining authors report no conflict of interest., (Copyright © 2024 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

The African leopard ( Panthera pardus pardus ) has lost a significant proportion of its historical range, notably in north-western Africa and South Africa. Recent studies have explored the genetic diversity and population structure of African leopards across the continent. A notable genetic observation is the presence of two divergent mitochondrial lineages, PAR-I and PAR-II. Both lineages appeared to be distributed widely, with PAR-II frequently found in southern Africa. Until now, no study has attempted to date the emergence of either lineage, assess haplotype distribution, or explore their evolutionary histories in any detail. To investigate these underappreciated questions, we compiled the largest and most geographically representative leopard data set of the mitochondrial NADH-5 gene to date. We combined samples ( n = 33) collected in an altitudinal transect across the Mpumalanga province of South Africa, where two populations of leopard are known to be in genetic contact, with previously published sequences of African leopard ( n = 211). We estimate that the maternal PAR-I and PAR-II lineages diverged approximately 0.7051 (0.4477-0.9632) million years ago (Ma). Through spatial and demographic analyses, we show that while PAR-I underwent a mid-Pleistocene population expansion resulting in several closely related haplotypes with little geographic structure across much of its range, PAR-II remained at constant size and may even have declined slightly in the last 0.1 Ma. The higher genetic drift experienced within PAR-II drove a greater degree of structure with little haplotype sharing and unique haplotypes in central Africa, the Cape, KwaZulu-Natal and the South African Highveld. The phylogeographic structure of PAR-II, with its increasing frequency southward and its exclusive occurrence in south-eastern South Africa, suggests that this lineage may have been isolated in South Africa during the mid-Pleistocene. This hypothesis is supported by historical changes in paleoclimate that promoted intense aridification around the Limpopo Basin between 1.0-0.6 Ma, potentially reducing gene flow and promoting genetic drift. Interestingly, we ascertained that the two nuclear DNA populations identified by a previous study as East and West Mpumalanga correspond to PAR-I and PAR-II, respectively, and that they have come into secondary contact in the Lowveld region of South Africa. Our results suggest a subdivision of African leopard mtDNA into two clades, with one occurring almost exclusively in South Africa, and we identify the potential environmental drivers of this observed structure. We caution that our results are based on a single mtDNA locus, but it nevertheless provides a hypothesis that can be further tested with a dense sample of nuclear DNA data, preferably whole genomes. If our interpretation holds true, it would provide the first genetic explanation for the smaller observed size of leopards at the southernmost end of their range in Africa., Competing Interests: Jannie Coetzee is employed by Mpumalanga Tourism and Parks Agency. The authors declare that they have no competing interests., (© 2024 Morris et al.)