Overexpression of the astrocyte glutamate transporter GLT1 exacerbates phrenic motor neuron degeneration, diaphragm compromise, and forelimb motor dysfunction following cervical contusion spinal cord injury.

A major portion of spinal cord injury (SCI) cases affect midcervical levels, the location of the phrenic motor neuron (PhMN) pool that innervates the diaphragm. While initial trauma is uncontrollable, a valuable opportunity exists in the hours to days following SCI for preventing PhMN loss and consequent respiratory dysfunction that occurs during secondary degeneration. One of the primary causes of secondary injury is excitotoxic cell death due to dysregulation of extracellular glutamate homeostasis. GLT1, mainly expressed by astrocytes, is responsible for the vast majority of functional uptake of extracellular glutamate in the CNS, particularly in spinal cord. We found that, in bacterial artificial chromosome-GLT1-enhanced green fluorescent protein reporter mice following unilateral midcervical (C4) contusion SCI, numbers of GLT1-expressing astrocytes in ventral horn and total intraspinal GLT1 protein expression were reduced soon after injury and the decrease persisted for ≥6 weeks. We used intraspinal delivery of adeno-associated virus type 8 (AAV8)-Gfa2 vector to rat cervical spinal cord ventral horn for targeting focal astrocyte GLT1 overexpression in areas of PhMN loss. Intraspinal delivery of AAV8-Gfa2-GLT1 resulted in transduction primarily of GFAP(+) astrocytes that persisted for ≥6 weeks postinjury, as well as increased intraspinal GLT1 protein expression. Surprisingly, we found that astrocyte-targeted GLT1 overexpression increased lesion size, PhMN loss, phrenic nerve axonal degeneration, and diaphragm neuromuscular junction denervation, and resulted in reduced functional diaphragm innervation as assessed by phrenic nerve-diaphragm compound muscle action potential recordings. These results demonstrate that GLT1 overexpression via intraspinal AAV-Gfa2-GLT1 delivery exacerbates neuronal damage and increases respiratory impairment following cervical SCI

Sexual risk behavior and pregnancy in detained adolescent females: a study in Dutch detention centers

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to investigate the lifetime prevalence of teenage pregnancy in the histories of detained adolescent females and to examine the relationship between teenage pregnancy on the one hand and mental health and sexuality related characteristics on the other.</p> <p>Methods</p> <p>Of 256 admitted detained adolescent females aged 12–18 years, a representative sample (N = 212, 83%) was examined in the first month of detention. Instruments included a semi-structured interview, standardized questionnaires and file information on pregnancy, sexuality related characteristics (sexual risk behavior, multiple sex partners, sexual trauma, lack of assertiveness in sexual issues and early maturity) and mental health characteristics (conduct disorder, alcohol and drug use disorder and suicidality).</p> <p>Results</p> <p>Approximately 20% of the participants reported having been pregnant (before detention), although none had actually given birth. Sexuality related characteristics were more prevalent in the pregnancy group, while this was not so for the mental health characteristics. Age at assessment, early maturity, sexual risk behavior, and suicidality turned out to be the best predictors for pregnancy.</p> <p>Conclusion</p> <p>The lifetime prevalence of pregnancy in detained adolescent females is high and is associated with both sexuality related risk factors and mental health related risk factors. Therefore, prevention and intervention programs targeting sexual risk behavior and mental health are warranted during detention.</p

Developing key performance indicators to measure the progress of regional regulatory convergence and cooperation in Asia-Pacific Economic Cooperation (APEC)

Abstract Regulatory convergence and cooperation among the authorities in the field of medical products (medicines and medical devices) are essential to deliver safe and efficacious products quickly to patients. APEC established the Regulatory Harmonization Steering Committee (RHSC) to advance this cause among member economies. This paper identifies four areas of appropriate regulatory practice in which APEC economies could converge, and explores the feasible processes of how APEC economies could cooperate in order to bring about realization of a maximum level of regulatory convergence by 2020

Performances of C-BORD's Tagged Neutron Inspection System for Explosives and Illicit Drugs Detection in Cargo Containers

In the frame of the effective Container inspection at BORDer control points (C-BORD) project [H2020 program of the European Union (EU)], a Rapidly Relocatable Tagged Neutron Inspection System (RRTNIS) has been developed for a nonintrusive inspection of cargo containers, aiming at explosives and other illicit goods detection. Twenty large-volume NaI detectors are used to determine the elements composing inspected materials from their specific gamma-ray spectra signatures induced by fast neutrons. The RRTNIS inspection is focused on a specific suspect area selected by X-ray radiography. An unfolding algorithm decomposes the energy spectrum of this suspect area on a database of pure element gamma signatures. A classification is then performed between inorganic materials, such as metals, ceramics, or chemicals, and organic materials like wood, fabrics, or plastic goods. Concerning organic materials, the obtained elemental proportions of carbon, nitrogen, and oxygen allow discriminating explosives from illicit drugs and benign substances. This article reports on the final laboratory tests performed at Commissariat à \text{I}^\prime Énergie Atomique et aux Énergies Alternatives (CEA) Saclay, France, to assess the RRTNIS detection performances before further demonstration tests in a real seaport environment. Simulants of explosives and illicit drugs have been hidden at different depths inside iron or wood cargo materials, which are representative of the different neutron and gamma attenuation properties encountered in real cargo containers. Hundreds of experiments have been performed, showing that a few kilograms of explosives or narcotics can be detected by the RRTNIS in 10-min inspections

Persistent at-level thermal hyperalgesia and tactile allodynia accompany chronic neuronal and astrocyte activation in superficial dorsal horn following mouse cervical contusion spinal cord injury.

In humans, sensory abnormalities, including neuropathic pain, often result from traumatic spinal cord injury (SCI). SCI can induce cellular changes in the CNS, termed central sensitization, that alter excitability of spinal cord neurons, including those in the dorsal horn involved in pain transmission. Persistently elevated levels of neuronal activity, glial activation, and glutamatergic transmission are thought to contribute to the hyperexcitability of these dorsal horn neurons, which can lead to maladaptive circuitry, aberrant pain processing and, ultimately, chronic neuropathic pain. Here we present a mouse model of SCI-induced neuropathic pain that exhibits a persistent pain phenotype accompanied by chronic neuronal hyperexcitability and glial activation in the spinal cord dorsal horn. We generated a unilateral cervical contusion injury at the C5 or C6 level of the adult mouse spinal cord. Following injury, an increase in the number of neurons expressing ΔFosB (a marker of chronic neuronal activation), persistent astrocyte activation and proliferation (as measured by GFAP and Ki67 expression), and a decrease in the expression of the astrocyte glutamate transporter GLT1 are observed in the ipsilateral superficial dorsal horn of cervical spinal cord. These changes have previously been associated with neuronal hyperexcitability and may contribute to altered pain transmission and chronic neuropathic pain. In our model, they are accompanied by robust at-level hyperaglesia in the ipsilateral forepaw and allodynia in both forepaws that are evident within two weeks following injury and persist for at least six weeks. Furthermore, the pain phenotype occurs in the absence of alterations in forelimb grip strength, suggesting that it represents sensory and not motor abnormalities. Given the importance of transgenic mouse technology, this clinically-relevant model provides a resource that can be used to study the molecular mechanisms contributing to neuropathic pain following SCI and to identify potential therapeutic targets for the treatment of chronic pathological pain

Microbial community structure and relationship with physicochemical properties of soil stockpiles in selected South African opencast coal mines

At present, there is no comprehensive soil quality assessment practice for soil stockpiles in the South African coal mining industry. Soil microorganisms and enzymes are suitable indicators for soil quality monitoring. Therefore, this study investigated the microbial community and enzyme (beta-glucosidase and urease) activities in soil stockpiles of opencast coal mines in the coal-rich region of South Africa. Soil stockpiles of three opencast coal mines were sampled at depths of 0–20 cm (‘topsoil’) and >20 cm (‘subsoil’) across three seasons. Beta-glucosidase and urease activities were mostly higher in soil stockpiles than in unmined soils and were significantly influenced (P 0.05) influenced by soil properties, whereas microbial communities of subsoils were significantly (P < 0.05) influenced by pH, organic carbon, total nitrogen and phosphorus contents. Furthermore, operational taxonomic units (OTUs) belonging to genera of known phytobeneficial species such as Azomonas, Aureobasidium, Phialocephala, Phoma and Sordariomycetes were detected in these soils. Overall, results suggest that the microbial community structure and diversity observed in stockpiles is impaired (compared to the unmined site), although variations in the microbial community structure of soil stockpiles across seasons are site-specific. The impaired microbial community of stockpiles may have negative implications on soil biological processes driven by microbes; especially those that are critical for nutrient cycling and ecosystem sustainability. More importantly, such alteration in soil biodiversity may impair post-mining land use capability of stockpile soil

Unilateral contusion SCI induced a loss of ventral horn motor neurons at the injury epicenter.

<p>Harvested tissue was stained with Cresyl violet and Eriochrome cyanine. At the level of the laminectomy, uninjured control animals (A) exhibited large motor neurons in the ventral horn (arrowheads). At six weeks post-injury, animals receiving unilateral C5 (B) or C6 (C) contusion SCI showed a loss of these motor neurons at the injury epicenter but not 1.0 mm caudal to the injury (D). The spread of ventral horn motor neuron loss was approximately 1.0 mm rostrally and 1.0 mm caudally (2.0 mm total) from the epicenter (E). Immunohistochemical analyses of the injury models were performed in laminae I–II and lamina III of the cervical spinal cord dorsal horn (F–G). Lam = laminectomy.</p

Enhanced cell proliferation, including proliferation of astrocytes, was evident after cervical contusion SCI.

<p>In the superficial laminae of the injured ipsilateral dorsal horn, we observed cells co-expressing GFAP and Ki67 (A), representing activated and proliferating astrocytes. In laminectomy control animals, little to no cell proliferation was evident (B). However, the number of Ki67-positive cells was significantly increased at two weeks (C) and six weeks (D) after injury on the ipsilateral side both at the level of and caudal to the injury (E). Additionally, at two weeks, there was a significant increase in proliferating cells contralaterally at the injury site (E). At both two and six weeks, a significant percentage of Ki67-positive cells were also either GFAP-positive or CD11b-positive (F). Compared to laminectomy (G), the intensity of CD11b expression in the superficial dorsal horn was greater in animals with C6 SCI at both two (H–I) and six (I) weeks after injury. This increase was significant at the injury site both ipsilaterally and contralaterally, as well as caudal to the injury on the contralateral side (I). * = p<0.05; ** = p<0.01; **** = p<0.0001.</p