Effects of lipopolysaccharide-induced inflammation on expression of growth-associated genes by corticospinal neurons

Background: Inflammation around cell bodies of primary sensory neurons and retinal ganglion cells enhances expression of neuronal growth-associated genes and stimulates axonal regeneration. We have asked if inflammation would have similar effects on corticospinal neurons, which normally show little response to spinal cord injury. Lipopolysaccharide (LPS) was applied onto the pial surface of the motor cortex of adult rats with or without concomitant injury of the corticospinal tract at C4. Inflammation around corticospinal tract cell bodies in the motor cortex was assessed by immunohistochemistry for OX42 ( a microglia and macrophage marker). Expression of growth-associated genes c-jun, ATF3, SCG10 and GAP-43 was investigated by immunohistochemistry or in situ hybridisation.Results: Application of LPS induced a gradient of inflammation through the full depth of the motor cortex and promoted c-Jun and SCG10 expression for up to 2 weeks, and GAP-43 upregulation for 3 days by many corticospinal neurons, but had very limited effects on neuronal ATF3 expression. However, many glial cells in the subcortical white matter upregulated ATF3. LPS did not promote sprouting of anterogradely labelled corticospinal axons, which did not grow into or beyond a cervical lesion site.Conclusion: Inflammation produced by topical application of LPS promoted increased expression of some growth-associated genes in the cell bodies of corticospinal neurons, but was insufficient to promote regeneration of the corticospinal tract

ATF3 upregulation in glia during Wallerian degeneration: differential expression in peripheral nerves and CNS white matter

Background: Many changes in gene expression occur in distal stumps of injured nerves but the transcriptional control of these events is poorly understood. We have examined the expression of the transcription factors ATF3 and c-Jun by non-neuronal cells during Wallerian degeneration following injury to sciatic nerves, dorsal roots and optic nerves of rats and mice, using immunohistochemistry and in situ hybridization.Results: Following sciatic nerve injury-transection or transection and reanastomosis-ATF3 was strongly upregulated by endoneurial, but not perineurial cells, of the distal stumps of the nerves by 1 day post operation (dpo) and remained strongly expressed in the endoneurium at 30 dpo when axonal regeneration was prevented. Most ATF3+ cells were immunoreactive for the Schwann cell marker, S100. When the nerve was transected and reanastomosed, allowing regeneration of axons, most ATF3 expression had been downregulated by 30 dpo. ATF3 expression was weaker in the proximal stumps of the injured nerves than in the distal stumps and present in fewer cells at all times after injury. ATF3 was upregulated by endoneurial cells in the distal stumps of injured neonatal rat sciatic nerves, but more weakly than in adult animals. ATF3 expression in transected sciatic nerves of mice was similar to that in rats. Following dorsal root injury in adult rats, ATF3 was upregulated in the part of the root between the lesion and the spinal cord (containing Schwann cells), beginning at 1 dpo, but not in the dorsal root entry zone or in the degenerating dorsal column of the spinal cord. Following optic nerve crush in adult rats, ATF3 was found in some cells at the injury site and small numbers of cells within the optic nerve displayed weak immunoreactivity. The pattern of expression of c-Jun in all types of nerve injury was similar to that of ATF3.Conclusion: These findings raise the possibility that ATF3/c-Jun heterodimers may play a role in regulating changes in gene expression necessary for preparing the distal segments of injured peripheral nerves for axonal regeneration. The absence of the ATF3 and c-Jun from CNS glia during Wallerian degeneration may limit their ability to support regeneration

Analysis of axonal regeneration in the central and peripheral nervous systems of the NG2-deficient mouse

<p>Abstract</p> <p>Background</p> <p>The chondroitin sulphate proteoglycan NG2 blocks neurite outgrowth in vitro and has been proposed as a major inhibitor of axonal regeneration in the CNS. Although a substantial body of evidence underpins this hypothesis, it is challenged by recent findings including strong expression of NG2 in regenerating peripheral nerve.</p> <p>Results</p> <p>We studied axonal regeneration in the PNS and CNS of genetically engineered mice that do not express NG2, and in sex and age matched wild-type controls. In the CNS, we used anterograde tracing with BDA to study corticospinal tract (CST) axons after spinal cord injury and transganglionic labelling with CT-HRP to trace ascending sensory dorsal column (DC) axons after DC lesions and a conditioning lesion of the sciatic nerve. Injury to these fibre tracts resulted in no difference between knockout and wild-type mice in the ability of CST axons or DC axons to enter or cross the lesion site. Similarly, after dorsal root injury (with conditioning lesion), most regenerating dorsal root axons failed to grow across the dorsal root entry zone in both transgenic and wild-type mice.</p> <p>Following sciatic nerve injuries, functional recovery was assessed by analysis of the toe-spreading reflex and cutaneous sensitivity to Von Frey hairs. Anatomical correlates of regeneration were assessed by: retrograde labelling of regenerating dorsal root ganglion (DRG) cells with DiAsp; immunostaining with PGP 9.5 to visualise sensory reinnervation of plantar hindpaws; electron microscopic analysis of regenerating axons in tibial and digital nerves; and by silver-cholinesterase histochemical study of motor end plate reinnervation. We also examined functional and anatomical correlates of regeneration after injury of the facial nerve by assessing the time taken for whisker movements and corneal reflexes to recover and by retrograde labelling of regenerated axons with Fluorogold and DiAsp. None of the anatomical or functional analyses revealed significant differences between wild-type and knockout mice.</p> <p>Conclusion</p> <p>These findings show that NG2 is unlikely to be a major inhibitor of axonal regeneration after injury to the CNS, and, further, that NG2 is unlikely to be necessary for regeneration or functional recovery following peripheral nerve injury.</p

The effect of processing treatments on the shelf life and nutritional quality of green chilli (Capsicum annuum L.) powder

An attempt was undertaken to investigate the effect of various common processing treatments, such as (a) without pedicle and cut longitudinally plus treated with 0.01% potassium metabisulphite (KMS), (b) without pedicle and sliced, (c) without pedicle as a whole, and (d) as a normal whole green chilli with pedicle, on the shelf life during storage in high density polyethylene (HDPE) and low density polyethylene (LDPE) packages at room temperature. The nutritional quality in terms of proximate compositions, Vitamin-C, beta-carotene and mineral contents of green chilli powder were also assessed. The chilli powder from the treatment (a) showed the highest stability up to 195 days in the HDPE pouches. In relation to proximate compositions and mineral contents, the processing treatments had a significant effect on them, except for Vitamin-C content at P<.0001. The results showed that the nutritional quality in all the samples of green chilli powder was better than that of the red chilli powder. Vitamin C content was reduced around 50% in all the samples due to the processing, while beta-carotene content was significantly increased as compared to the fresh green chilli. A simple calculation revealed the potential of green chilli powder as a value added and alternative spice

Studies of annealing impact on the morphological, opto-dielectric and mechanical behaviors of molybdenum-doped CrN coatings

In the present study, molybdenum doped chromium nitride coatings deposited onto silicon substrates via unbalanced magnetron sputtering, in as-deposited and annealed conditions, at 500–800 °C in steps of 100 °C, were studied to reveal their temperature dependent structural, morphological, optical and mechanical behaviors. An analysis of these features was carried out using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), ultraviolet visible (UV–Vis) spectroscopy, nanoindentation and finite element modeling (FEM) techniques. XRD results exhibited a significant improvement in the crystallinity of the Molybdenum (Mo)-doped chromium nitride (CrN) coatings along (111) and (200) diffraction planes, as the annealing temperatures increased. The lattice parameters gradually decreased from 4.20 to 4.12 Å as the temperature increased. The same tendency was also observed for lattice microstrains and residual stresses. Smooth grain-like surfaces were observed by FESEM imaging techniques. At an annealing temperature of 700 °C, the spectral absorptance of Mo:CrN films attained its peak value (86%), whereas the energy band-gaps were reduced from 2.48 to 1.14 eV. The other optical parameters such as complex dielectric constants, Urbach energy values, and steepness parameters of these coatings were also discussed. The hardness and elastic modulus of the as-deposited Mo:CrN films were estimated to be 18.4 and 287 GPa, respectively. At a film thickness of 1.0 μm, the highest stress of 20 GPa was evaluated, via FEM studies, at the interface between the film and the substrate. As the film thickness was enhanced, the stress level decreased. At higher annealing temperatures, both the mechanical hardness (H) and the elastic modulus (E) of Mo-doped CrN coatings dwindled

Electrocatalytic and structural properties and computational calculation of PAN-EC-PC-TPAI-I2 gel polymer electrolytes for dye sensitized solar cell application

In this study, gel polymer electrolytes (GPEs) were prepared using polyacrylonitrile (PAN) polymer, ethylene carbonate (EC), propylene carbonate (PC) plasticizers and different compositions of tetrapropylammonium iodide (TPAI) salt. Linear sweep voltammetry (LSV) and electrochemical impedance spectroscopy (EIS) measurements were done using non-blocking Pt-electrode symmetric cells. The limiting current (Jlim), apparent diffusion coefficient of triiodide ions ðD* I3 Þ and exchange current were found to be 12.76 mA cm2 , 23.41 107 cm2 s 1 and 11.22–14.24 mA cm2 , respectively, for the GPE containing 30% TPAI. These values are the highest among the GPEs with different TPAI contents. To determine the ionic conductivity, the EIS technique was employed with blocking electrodes. The GPE containing 30% TPAI exhibited the lowest bulk impedance, Rb (22 U), highest ionic conductivity (3.62 103 S cm1 ) and lowest activation energy. Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) techniques were utilized for structural characterization. Functional group interactions among PAN, EC, PC and TPAI were studied in the FTIR spectra of the GPEs. An up-shift of the XRD peak indicates the polymer–salt interaction and possible complexation of the cation (TPA+ ion) with the lone pair of electrons containing site –C^N at the N atom in the host polymer matrix. On the other hand, computational study shows that TPAI-PAN based GPE possesses the lowest frontier orbital bandgap, which coincided with the enhanced electrochemical and electrocatalytic performance of GPE. The dyesensitized solar cell (DSSC) fabricated with these GPEs showed that the JSC (19.75 mA cm2 ) and VOC (553.8 mV) were the highest among the GPEs and hence the highest efficiency, h (4.76%), was obtained for the same electrolyte

Effects of social determinants on children’s health in informal settlements in Bangladesh and Kenya through an intersectionality lens: a study protocol

Introduction Several studies have shown that residents of urban informal settlements/slums are usually excluded and marginalised from formal social systems and structures of power leading to disproportionally worse health outcomes compared to other urban dwellers. To promote health equity for slum dwellers, requires an understanding of how their lived realities shape inequities especially for young children 0–4 years old (ie, underfives) who tend to have a higher mortality compared with non-slum children. In these proposed studies, we aim to examine how key Social Determinants of Health (SDoH) factors at child and household levels combine to affect under-five health conditions, who live in slums in Bangladesh and Kenya through an intersectionality lens. Methods and analysis The protocol describes how we will analyse data from the Nairobi Cross-sectional Slum Survey (NCSS 2012) for Kenya and the Urban Health Survey (UHS 2013) for Bangladesh to explore how SDoH influence under-five health outcomes in slums within an intersectionality framework. The NCSS 2012 and UHS 2013 samples will consist of 2199 and 3173 under-fives, respectively. We will apply Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy approach. Some of SDoH characteristics to be considered will include those of children, head of household, mothers and social structure characteristics of household. The primary outcomes will be whether a child had diarrhoea, cough, fever and acute respiratory infection (ARI) 2 weeks preceding surveys. Ethics and dissemination The results will be disseminated in international peer-reviewed journals and presented in events organised by the Accountability and Responsiveness in Informal Settlements for Equity consortium and international conferences. Ethical approval was not required for these studies. Access to the NCSS 2012 has been given by Africa Population and Health Center and UHS 2013 is freely availabl

The burden of antimicrobial resistance in the Americas in 2019: a cross-country systematic analysis

Background Antimicrobial resistance (AMR) is an urgent global health challenge and a critical threat to modern health care. Quantifying its burden in the WHO Region of the Americas has been elusive—despite the region’s long history of resistance surveillance. This study provides comprehensive estimates of AMR burden in the Americas to assess this growing health threat. Methods We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen–drug combinations for countries in the WHO Region of the Americas in 2019. We obtained data from mortality registries, surveillance systems, hospital systems, systematic literature reviews, and other sources, and applied predictive statistical modelling to produce estimates of AMR burden for all countries in the Americas. Five broad components were the backbone of our approach: the number of deaths where infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of pathogens resistant to an antibiotic class, and the excess risk of mortality (or duration of an infection) associated with this resistance. We then used these components to estimate the disease burden by applying two counterfactual scenarios: deaths attributable to AMR (compared to an alternative scenario where resistant infections are replaced with susceptible ones), and deaths associated with AMR (compared to an alternative scenario where resistant infections would not occur at all). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. Findings We estimated 569,000 deaths (95% UI 406,000–771,000) associated with bacterial AMR and 141,000 deaths (99,900–196,000) attributable to bacterial AMR among the 35 countries in the WHO Region of the Americas in 2019. Lower respiratory and thorax infections, as a syndrome, were responsible for the largest fatal burden of AMR in the region, with 189,000 deaths (149,000–241,000) associated with resistance, followed by bloodstream infections (169,000 deaths [94,200–278,000]) and peritoneal/intra-abdominal infections (118,000 deaths [78,600–168,000]). The six leading pathogens (by order of number of deaths associated with resistance) were Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Together, these pathogens were responsible for 452,000 deaths (326,000–608,000) associated with AMR. Methicillin-resistant S. aureus predominated as the leading pathogen–drug combination in 34 countries for deaths attributable to AMR, while aminopenicillin-resistant E. coli was the leading pathogen–drug combination in 15 countries for deaths associated with AMR. Interpretation Given the burden across different countries, infectious syndromes, and pathogen–drug combinations, AMR represents a substantial health threat in the Americas. Countries with low access to antibiotics and basic health-care services often face the largest age-standardised mortality rates associated with and attributable to AMR in the region, implicating specific policy interventions. Evidence from this study can guide mitigation efforts that are tailored to the needs of each country in the region while informing decisions regarding funding and resource allocation. Multisectoral and joint cooperative efforts among countries will be a key to success in tackling AMR in the Americas.publishedVersio

CSF Rhinorrhea After Endonasal Intervention to the Skull Base (CRANIAL) — Part 2:Impact of COVID-19

Background During the pandemic, there has been a concern about the increased risk of perioperative mortality for patients with COVID-19, and the transmission risk to healthcare workers, particularly during endonasal neurosurgical operations. The Pituitary Society produced recommendations to guide management during this era. We sought to assess contemporary neurosurgical practice and the impact of COVID-19. Methods A multicentre, prospective, observational cohort study was conducted at twelve tertiary neurosurgical units (UK and Ireland). Data were collected from March 23rd-July 31st, 2020 inclusive. Data points collected were patient demographics, pre-operative COVID-19 testing, intra-operative operative modifications, and 30-day COVID infection rates. Results 124 patients were included. 116 patients (n=116/124, 94%) underwent COVID-19 testing pre-operatively (TSA: 97/105, 92%; EEA: 19/19, 100%). One patient (n=1/115, 1%) tested positively for COVID-19 pre-operatively, requiring a delay of operation until the infection was confirmed as resolved. Asides from transient diabetes insipidus; no other complications were reported for this case. All theatre staff wore at least level 2 PPE. Adaptations to surgical techniques included minimising drilling, draping modifications, and using nasal iodine wash. At 30 days postoperatively, there was no evidence of COVID infection (symptoms or on formal testing) in our cohort, and no mortality. Conclusions Preoperative screening protocols and operative modifications have facilitated endonasal neurosurgery during the COVID-19 pandemic, with Pituitary Society guidelines followed for the majority of these operations. There was no evidence of COVID infection in our cohort, and no mortality, supporting the use of risk mitigation strategies to continue endonasal neurosurgery in subsequent pandemic waves