Neuropathic pain in low back-related leg pain patients: What is the evidence of prevalence, characteristics, and prognosis in primary care? A systematic review of the literature.

This systematic review synthesizes literature describing prevalence, characteristics and prognosis of low back-related leg pain (LBLP) patients with neuropathic pain in primary care and/or similar settings. Inclusion and exclusion criteria were developed and used by independent reviewers to screen citations for eligibility. The initial search yielded 24,948 citations; after screening 12 studies were included. Neuropathic pain was identified by case ascertainment tools (n=5), by clinical history with examination (n=4), and by LBLP samples assumed neuropathic (n=3). Neuropathic pain prevalence varied from 19% to 80%. There was consistent evidence for higher back-related disability (n=3), poorer health-related quality of life (n=2) and some evidence for more severe depression (n=2), anxiety (n=3) and pain intensity (n=4) in patients with neuropathic pain. Results were less consistent when cases were identified through clinical history plus examination than those identified using case ascertainment tools. Prognosis (n=1) of LBLP patients with neuropathic pain was worse compared to those without, in all outcomes (leg pain intensity, leg and back-related disability, self-reported general health) except back pain intensity. No studies described prognostic factors. This systematic review highlights the evidence gap in neuropathic pain in LBLP in primary care, especially with respect to prognosis. PERSPECTIVE: Patients with low back-related leg pain may have neuropathic pain. This systematic review emphasises the paucity of evidence describing the characteristics and prognosis of neuropathic pain in this patient population. Future research investigating prognosis of these patients with neuropathic pain is likely to contribute to better understanding and management

Prevalence, Characteristics and Clinical Course of Neuropathic Pain in Primary Care Patients Consulting with Low Back-related Leg Pain.

OBJECTIVES: Little is known about the epidemiology of neuropathic pain in primary care patients consulting with low back-related leg pain. We aimed to describe prevalence, characteristics and clinical course of low back-related leg pain patients with and without neuropathic pain, consulting with their family doctor in the UK. METHODS: This was a prospective cohort study. Data were collected using a standardised baseline clinical examination and self-report questionnaires at baseline, 4, 12 and 36-months. We identified cases of neuropathic pain using three definitions: two based on clinical diagnosis (sciatica, with and without evidence of nerve root compression on MRI), one on the self-report version of Leeds Assessment for Neurological Symptoms and Signs (S-LANSS). Differences between patients with and without neuropathic pain were analysed comparing each definition. Clinical course (mean pain intensity measured as the highest of leg or back pain intensity: mean of three Numerical Rating Scales, each 0-10) was investigated using linear mixed models over 36-months. RESULTS: Prevalence of neuropathic pain varied from 48% to 74% according to definition used. At baseline, patients with neuropathic pain had more severe leg pain intensity, lower pain self-efficacy, more patients had sensory loss than those without. Distinct profiles were apparent depending on neuropathic pain definition. Mean pain intensity reduced after 4-months (6.1 to 3.9 (sciatica)), most rapidly in cases defined by clinical diagnosis. DISCUSSION: This research provides new information on the clinical course of neuropathic pain and a better understanding of neuropathic pain in low back-related leg pain patients consulting in primary care

Review of small-angle coronagraphic techniques in the wake of ground-based second-generation adaptive optics systems

Small-angle coronagraphy is technically and scientifically appealing because it enables the use of smaller telescopes, allows covering wider wavelength ranges, and potentially increases the yield and completeness of circumstellar environment - exoplanets and disks - detection and characterization campaigns. However, opening up this new parameter space is challenging. Here we will review the four posts of high contrast imaging and their intricate interactions at very small angles (within the first 4 resolution elements from the star). The four posts are: choice of coronagraph, optimized wavefront control, observing strategy, and post-processing methods. After detailing each of the four foundations, we will present the lessons learned from the 10+ years of operations of zeroth and first-generation adaptive optics systems. We will then tentatively show how informative the current integration of second-generation adaptive optics system is, and which lessons can already be drawn from this fresh experience. Then, we will review the current state of the art, by presenting world record contrasts obtained in the framework of technological demonstrations for space-based exoplanet imaging and characterization mission concepts. Finally, we will conclude by emphasizing the importance of the cross-breeding between techniques developed for both ground-based and space-based projects, which is relevant for future high contrast imaging instruments and facilities in space or on the ground.Comment: 21 pages, 7 figure

Ultrafast photochemistry produces superbright short-wave infrared dots for low-dose in vivo imaging

12 p.-5 fig.Optical probes operating in the second near-infrared window (NIR-II, 1,000-1,700 nm), where tissues are highly transparent, have expanded the applicability of fluorescence in the biomedical field. NIR-II fluorescence enables deep-tissue imaging with micrometric resolution in animal models, but is limited by the low brightness of NIR-II probes, which prevents imaging at low excitation intensities and fluorophore concentrations. Here, we present a new generation of probes (Ag2S superdots) derived from chemically synthesized Ag2S dots, on which a protective shell is grown by femtosecond laser irradiation. This shell reduces the structural defects, causing an 80-fold enhancement of the quantum yield. PEGylated Ag2S superdots enable deep-tissue in vivo imaging at low excitation intensities (<10 mW cm-2) and doses (<0.5 mg kg-1), emerging as unrivaled contrast agents for NIR-II preclinical bioimaging. These results establish an approach for developing superbright NIR-II contrast agents based on the synergy between chemical synthesis and ultrafast laser processing.Authors thank Dr A. Benayas (CICECO, U. Aveiro, Portugal), Prof G. Lifante and Prof J. García Sole (UAM) for helpful discussions. This work has been founded by Ministerio de Economı́a y Competitividad-MINECO (MAT2017-83111R and MAT2016-75362-C3-1-R) and the Comunidad de Madrid (B2017/BMD-3867 RENIM-CM) co-financed by European Structural and Investment Fund. D.M.-G. thanks UCM-Santander for a predoctoral contract (CT17/17-CT18/17). We thank the staff at the ICTS-National Centre for Electron Microscopy at the UCM for the help in the electron microscopy studies and C.M. at the beamline BL22-CLAESS of the Spanish synchrotron ALBA for his help in the XANES experiments. We also thank J.G.I at the Ultrafast Laser Laboratory at UCM for his help and fruitful discussion. Y.S. acknowledges the support from the China Scholarship Council (CSC File No. 201806870023). Additional funding was provided by the European Commission Horizon 2020 project NanoTBTech, the Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal project IMP18_38 (2018/0265). Ajoy K. Kar and Mark D. Mackenzie acknowledge support from the UK Engineering and Physical Sciences Research Council (Project CHAMP, EP/M015130/1). C. Jacinto thanks the financial support of the Brazilian agencies: CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) through the grants: Projeto Universal Nr. 431736/2018-9 and Scholarship in Research Productivity 1C under the Nr. 304967/20181; FINEP (Financiadora de Estudos e Projetos) through the grants INFRAPESQ-11 and INFRAPESQ-12; FAPEAL (Fundação de Amparo à Pesquisa do Estado de Alagoas) grant Nr. 1209/2016. H. D. A. Santos was supported by a graduate studentship from CNPq and by a sandwich doctoral program (PDSE-CAPES) developed at Universidad Autonoma de Madrid, Spain, Project Nr. 88881/2016-01.Peer reviewe

Mendelian gene identification through mouse embryo viability screening.

BACKGROUND: The diagnostic rate of Mendelian disorders in sequencing studies continues to increase, along with the pace of novel disease gene discovery. However, variant interpretation in novel genes not currently associated with disease is particularly challenging and strategies combining gene functional evidence with approaches that evaluate the phenotypic similarities between patients and model organisms have proven successful. A full spectrum of intolerance to loss-of-function variation has been previously described, providing evidence that gene essentiality should not be considered as a simple and fixed binary property. METHODS: Here we further dissected this spectrum by assessing the embryonic stage at which homozygous loss-of-function results in lethality in mice from the International Mouse Phenotyping Consortium, classifying the set of lethal genes into one of three windows of lethality: early, mid, or late gestation lethal. We studied the correlation between these windows of lethality and various gene features including expression across development, paralogy and constraint metrics together with human disease phenotypes. We explored a gene similarity approach for novel gene discovery and investigated unsolved cases from the 100,000 Genomes Project. RESULTS: We found that genes in the early gestation lethal category have distinct characteristics and are enriched for genes linked with recessive forms of inherited metabolic disease. We identified several genes sharing multiple features with known biallelic forms of inborn errors of the metabolism and found signs of enrichment of biallelic predicted pathogenic variants among early gestation lethal genes in patients recruited under this disease category. We highlight two novel gene candidates with phenotypic overlap between the patients and the mouse knockouts. CONCLUSIONS: Information on the developmental period at which embryonic lethality occurs in the knockout mouse may be used for novel disease gene discovery that helps to prioritise variants in unsolved rare disease cases

Recent Surveys in the Forests of Ulu Segama Malua, Sabah, Malaysia, Show That Orang-utans (P. p. morio) Can Be Maintained in Slightly Logged Forests

BACKGROUND: Today the majority of wild great ape populations are found outside of the network of protected areas in both Africa and Asia, therefore determining if these populations are able to survive in forests that are exploited for timber or other extractive uses and how this is managed, is paramount for their conservation. METHODOLOGY/PRINCIPAL FINDINGS: In 2007, the "Kinabatangan Orang-utan Conservation Project" (KOCP) conducted aerial and ground surveys of orang-utan (Pongo pygmaeus morio) nests in the commercial forest reserves of Ulu Segama Malua (USM) in eastern Sabah, Malaysian Borneo. Compared with previous estimates obtained in 2002, our recent data clearly shows that orang-utan populations can be maintained in forests that have been lightly and sustainably logged. However, forests that are heavily logged or subjected to fast, successive coupes that follow conventional extraction methods, exhibit a decline in orang-utan numbers which will eventually result in localized extinction (the rapid extraction of more than 100 m(3) ha(-1) of timber led to the crash of one of the surveyed sub-populations). Nest distribution in the forests of USM indicates that orang-utans leave areas undergoing active disturbance and take momentarily refuge in surrounding forests that are free of human activity, even if these forests are located above 500 m asl. Displaced individuals will then recolonize the old-logged areas after a period of time, depending on availability of food sources in the regenerating areas. CONCLUSION/SIGNIFICANCE: These results indicate that diligent planning prior to timber extraction and the implementation of reduced-impact logging practices can potentially be compatible with great ape conservation