An environmental health guideline for the development of local health policy

GGD'en spelen een belangrijke rol in de advisering van gemeenten bij de ontwikkeling van gemeentelijke nota's lokaal gezondheidsbeleid. Deze nota's beogen een integrale aanpak van gezondheidsbeleid met daarbij zowel aandacht voor het bevorderen van een gezonde leefstijl, als voor het bevorderen van een goede sociale en fysieke omgeving. Deze richtlijn gaat in op het laatstgenoemde onderwerp: milieufactoren en kenmerken van de fysieke omgeving die in relatie staan tot gezondheid. De richtlijn geeft informatie over wet- en regelgeving, over bestuur en bestuurlijke processen en over beleid. Informatie die nuttig is voor het belangrijkste onderdeel van de richtlijn: een stappenplan om beleid op het gebied van milieu en gezondheid te ontwikkelen.Municipal health offices play an important role in the Netherlands in advising local government on the development of local health policy. Policy plans envisage an integral vision on health where attention is paid to both the promotion of a healthy lifestyle and a good social and physical environment. This guideline focuses on the last topic: environmental factors and characteristics of the physical environment in relation to health. It also provides information on legislation and regulation local government and governmental processes and health policy. To sum up, this information that will be useful in building up stepwise guidance for developing environmental health policy.VW

Functional Consequences of the Postnatal Switch From Neonatal to Mutant Adult Glycine Receptor α1 Subunits in the Shaky Mouse Model of Startle Disease

Mutations in GlyR α1 or β subunit genes in humans and rodents lead to severe startle disease characterized by rigidity, massive stiffness and excessive startle responses upon unexpected tactile or acoustic stimuli. The recently characterized startle disease mouse mutant shaky carries a missense mutation (Q177K) in the β8-β9 loop within the large extracellular N-terminal domain of the GlyR α1 subunit. This results in a disrupted hydrogen bond network around K177 and faster GlyR decay times. Symptoms in mice start at postnatal day 14 and increase until premature death of homozygous shaky mice around 4–6 weeks after birth. Here we investigate the in vivo functional effects of the Q177K mutation using behavioral analysis coupled to protein biochemistry and functional assays. Western blot analysis revealed GlyR α1 subunit expression in wild-type and shaky animals around postnatal day 7, a week before symptoms in mutant mice become obvious. Before 2 weeks of age, homozygous shaky mice appeared healthy and showed no changes in body weight. However, analysis of gait and hind-limb clasping revealed that motor coordination was already impaired. Motor coordination and the activity pattern at P28 improved significantly upon diazepam treatment, a pharmacotherapy used in human startle disease. To investigate whether functional deficits in glycinergic neurotransmission are present prior to phenotypic onset, we performed whole-cell recordings from hypoglossal motoneurons (HMs) in brain stem slices from wild-type and shaky mice at different postnatal stages. Shaky homozygotes showed a decline in mIPSC amplitude and frequency at P9-P13, progressing to significant reductions in mIPSC amplitude and decay time at P18-24 compared to wild-type littermates. Extrasynaptic GlyRs recorded by bath-application of glycine also revealed reduced current amplitudes in shaky mice compared to wild-type neurons, suggesting that presynaptic GlyR function is also impaired. Thus, a distinct, but behaviorally ineffective impairment of glycinergic synapses precedes the symptoms onset in shaky mice. These findings extend our current knowledge on startle disease in the shaky mouse model in that they demonstrate how the progression of GlyR dysfunction causes, with a delay of about 1 week, the appearance of disease symptoms

Mixed exciton–charge-transfer states in photosystem II: Stark spectroscopy on site–directed mutants

AbstractWe investigated the electronic structure of the photosystem II reaction center (PSII RC) in relation to the light-induced charge separation process using Stark spectroscopy on a series of site-directed PSII RC mutants from the cyanobacterium Synechocystis sp. PCC 6803. The site-directed mutations modify the protein environment of the cofactors involved in charge separation (PD1, PD2, ChlD1, and PheD1). The results demonstrate that at least two different exciton states are mixed with charge-transfer (CT) states, yielding exciton states with CT character: (PD2δ+PD1δ−ChlD1)∗673nm and (ChlD1δ+PheD1δ−)∗681nm (where the subscript indicates the wavelength of the electronic transition). Moreover, the CT state PD2+PD1− acquires excited-state character due to its mixing with an exciton state, producing (PD2+PD1−)δ∗684nm. We conclude that the states that initiate charge separation are mixed exciton-CT states, and that the degree of mixing between exciton and CT states determines the efficiency of charge separation. In addition, the results reveal that the pigment-protein interactions fine-tune the energy of the exciton and CT states, and hence the mixing between these states. This mixing ultimately controls the selection and efficiency of a specific charge separation pathway, and highlights the capacity of the protein environment to control the functionality of the PSII RC complex

Two different charge-separation pathways in photosystem II

Charge separation is an essential step in the conversion of solar energy into chemical energy in photosynthesis. To investigate this process, we performed transient absorption experiments at 77 K with various excitation conditions on the isolated Photosystem II reaction center preparations from spinach. The results have been analyzed by global and target analysis and demonstrate that at least two different excited states, (Ch

Disruption of a structurally important extracellular element in the Glycine Receptor leads to decreased synaptic integration and signaling resulting in Severe Startle Disease

Functional impairments or trafficking defects of inhibitory glycine receptors (GlyRs) have been linked to human hyperekplexia/startle disease and autism spectrum disorders. We found that a lack of synaptic integration of GlyRs, together with disrupted receptor function, is responsible for a lethal startle phenotype in a novel spontaneous mouse mutant shaky, caused by a missense mutation, Q177K, located in the extracellular β8–β9 loop of the GlyR α1 subunit. Recently, structural data provided evidence that the flexibility of the β8–β9 loop is crucial for conformational transitions during opening and closing of the ion channel and represents a novel allosteric binding site in Cys-loop receptors. We identified the underlying neuropathological mechanisms in male and female shaky mice through a combination of protein biochemistry, immunocytochemistry, and both in vivo and in vitro electrophysiology. Increased expression of the mutant GlyR α1Q177K subunit in vivo was not sufficient to compensate for a decrease in synaptic integration of α1Q177Kβ GlyRs. The remaining synaptic heteromeric α1Q177Kβ GlyRs had decreased current amplitudes with significantly faster decay times. This functional disruption reveals an important role for the GlyR α1 subunit β8–β9 loop in initiating rearrangements within the extracellular–transmembrane GlyR interface and that this structural element is vital for inhibitory GlyR function, signaling, and synaptic clustering

Revival of the magnetar PSR J1622-4950: observations with MeerKAT, Parkes, XMM-Newton, Swift, Chandra, and NuSTAR

New radio (MeerKAT and Parkes) and X-ray (XMM-Newton, Swift, Chandra, and NuSTAR) observations of PSR J1622-4950 indicate that the magnetar, in a quiescent state since at least early 2015, reactivated between 2017 March 19 and April 5. The radio flux density, while variable, is approximately 100x larger than during its dormant state. The X-ray flux one month after reactivation was at least 800x larger than during quiescence, and has been decaying exponentially on a 111+/-19 day timescale. This high-flux state, together with a radio-derived rotational ephemeris, enabled for the first time the detection of X-ray pulsations for this magnetar. At 5%, the 0.3-6 keV pulsed fraction is comparable to the smallest observed for magnetars. The overall pulsar geometry inferred from polarized radio emission appears to be broadly consistent with that determined 6-8 years earlier. However, rotating vector model fits suggest that we are now seeing radio emission from a different location in the magnetosphere than previously. This indicates a novel way in which radio emission from magnetars can differ from that of ordinary pulsars. The torque on the neutron star is varying rapidly and unsteadily, as is common for magnetars following outburst, having changed by a factor of 7 within six months of reactivation.Comment: Published in ApJ (2018 April 5); 13 pages, 4 figure

Expression of pathogenesis related genes in response to salicylic acid, methyl jasmonate and 1-aminocyclopropane-1-carboxylic acid in Malus hupehensis (Pamp.) Rehd

<p>Abstract</p> <p>Background</p> <p>Many studies have been done to find out the molecular mechanism of systemic acquired resistance (SAR) in plants in the past several decades. Numbers of researches have been carried out in the model plants such as arabidopsis, tobacco, rice and so on, however, with little work done in woody plants especially in fruit trees such as apple. Components of the pathway of SAR seem to be extremely conserved in the variety of species. <it>Malus hupehensis</it>, which is origin in China, is strong resistance with rootstock. In the study, we attempted to make the expression pattern of pathogenesis related (PR) genes which were downstream components of the SAR pathway in response to salicylic acid(SA), methyl jasmonate(MeJA) and 1-aminocyclopropane-1-carboxylic acid(ACC) in <it>Malus hupehensis</it>.</p> <p>Findings</p> <p>In order to analyze the expression pattern, the partial sequence of three PR genes from <it>Malus hupehensis</it>, <it>MhPR1</it>, <it>MhPR5 </it>and <it>MhPR8 </it>was isolated. These three PR genes were induced by SA, MeJA and ACC. However, <it>MhPR1</it>, <it>MhPR5 </it>and <it>MhPR8 </it>performed a distinct pattern of expression in different plant organs. <it>MhPR5 </it>and <it>MhPR8 </it>were basal expression in leaves, stems and roots, and <it>MhPR1 </it>was basal expression only in stems. The expression of <it>MhPR1</it>, <it>MhPR5 </it>and <it>MhPR8 </it>was enhanced during the first 48 h post-induced with SA, MeJA and ACC.</p> <p>Conclusions</p> <p>The results showed that a distinct pattern of expression of PR genes in <it>Malus hupehensis </it>which differed from the previous reports on model plants arabidopsis, tobacco and rice. <it>MhPR1</it>, <it>MhPR5 </it>and <it>MhPR8 </it>were induced by SA, MeJA and ACC, which were regarded as the marker genes in the SAR response in <it>Malus hupehensis</it>. In contrast with herbal plants, there could be specific signal pathway in response to SA, JA and ET for woody plants.</p

SKA telescope manager: a status update

The international Square Kilometre Array (SKA) project to build two radio interferometers is approaching the end of its design phase, and gearing up for the beginning of formal construction. A key part of this distributed Observatory is the overall software control system: the Telescope Manager (TM). The two telescopes, a Low frequency dipole array to be located in Western Australia (SKA-Low) and a Mid-frequency dish array to be located in South Africa (SKA-Mid) will be operated as a single Observatory, with its global headquarters (GHQ) based in the United Kingdom at Jodrell Bank. When complete it will be the most powerful radio observatory in the world. The TM software must combine the observatory operations based at the GHQ with the monitor and control operations of each telescope, covering the range of domains from proposal submission to the coordination and monitoring of the subsystems that make up each telescope. It must also monitor itself and provide a reliable operating platform. This paper will provide an update on the design status of TM, covering the make-up of the consortium delivering the design, a brief description of the key challenges and the top level architecture, and its software development plans for tackling the construction phase of the project. It will also briefly describe the consortium’s response to the SKA Project’s decision in the second half of 2016 to adopt the processes set out by the Software Engineering Institute (SEI) for system architecture design and documentation, including a re-evaluation of its deliverables, documentation and approach to internal reviews.publishe

Shorter courses of parenteral antibiotic therapy do not appear to influence response rates for children with acute hematogenous osteomyelitis: a systematic review

BACKGROUND: Acute hematogenous osteomyelitis (AHO) occurs primarily in children and is believed to evolve from bacteremia followed by localization of infection to the metaphysis of bones. Currently, there is no consensus on the route and duration of antimicrobial therapy to treat AHO. METHODS: We conducted a systematic review of a short versus long course of treatment for AHO due primarily to Staphylococcus aureus in children aged 3 months to 16 years. We searched Medline, Embase and the Cochrane trials registry for controlled trials. Clinical cure rate at 6 months was the primary outcome variable, and groups receiving less than 7 days of intravenous therapy were compared with groups receiving one week or longer of intravenous antimicrobials. RESULTS: 12 eligible prospective studies, one of which was randomized, were identified. The overall cure rate at 6 months for the short course of intravenous therapy was 95.2% (95% CI = 90.4, 97.7) compared to 98.8% (95% CI = 93.6, 99.8) for the longer course of therapy. There was no significant difference in the duration of oral therapy between the two groups. CONCLUSIONS: Given the potential increased morbidity and cost associated with longer courses of intravenous therapy, this finding should be confirmed through a randomized controlled equivalence trial