The two primary causes of surf zone injuries (SZIs)
worldwide, including fatal drowning and severe spinal injuries, are rip
currents (rips) and shore-break waves. SZIs also result from surfing and
...bodyboarding activity. In this paper we address the primary environmental
controls on SZIs along the high-energy meso–macro-tidal surf beach coast of
southwestern France. A total of 2523 SZIs recorded by lifeguards over 186 sample days
during the summers of 2007, 2009 and 2015 were combined with measured and/or
hindcast weather, wave, tide, and beach morphology data. All SZIs occurred
disproportionately on warm sunny days with low wind, likely because of
increased beachgoer numbers and hazard exposure. Relationships were
strongest for shore-break- and rip-related SZIs and weakest for surfing-related SZIs, the latter being also unaffected by tidal stage or range.
Therefore, the analysis focused on bathers. More shore-break-related SZIs
occur during shore-normal incident waves with average to below-average wave
height (significant wave height, Hs = 0.75–1.5 m) and around higher water
levels and large tide ranges when waves break on the steepest section of the
beach. In contrast, more rip-related drownings occur near neap low tide,
coinciding with maximised channel rip flow activity, under shore-normal
incident waves with Hs >1.25 m and mean wave periods longer
than 5 s. Additional drowning incidents occurred at spring high tide,
presumably due to small-scale swash rips. The composite wave and tide
parameters proposed by Scott et al. (2014) are key controlling factors
determining SZI occurrence, although the risk ranges are not necessarily
transferable to all sites. Summer beach and surf zone morphology is interannually highly
variable, which is critical to SZI patterns. The upper beach
slope can vary from 0.06 to 0.18 between summers, resulting in low and high
shore-break-related SZIs, respectively. Summers with coast-wide highly
(weakly) developed rip channels also result in widespread (scarce) rip-related drowning incidents. With life risk defined in terms of the number of
people exposed to life threatening hazards at a beach, the ability of
morphodynamic models to simulate primary beach morphology characteristics a
few weeks or months in advance is therefore of paramount importance for predicting
the primary surf zone life risks along this coast.
IMPORTANCE: A proportion of patients experience long-lasting symptoms following mild traumatic brain injury (MTBI). The postconcussion syndrome (PCS), included in the DSM-IV, has been proposed to ...describe this condition. Because these symptoms are subjective and common to other conditions, there is controversy whether PCS deserves to be identified as a diagnostic syndrome. OBJECTIVE: To assess whether persistent symptoms 3 months following head injury are specific to MTBI or whether they are better described as part of posttraumatic stress disorder (PTSD). DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective cohort study of injured patients recruited at the adult emergency department of the University Hospital of Bordeaux from December 4, 2007, to February 25, 2009. MAIN OUTCOMES AND MEASURES: At 3-month follow-up, we compared the prevalence and risk factors for PCS and PTSD. Multiple correspondence analyses were used to assess clustering of symptoms and their associations with the type of injury. RESULTS: We included 534 patients with head injury and 827 control patients with other nonhead injuries. Three months following the trauma, 21.2% of head-injured and 16.3% of nonhead-injured patients fulfilled the DSM-IV diagnosis of PCS; 8.8% of head-injured patients fulfilled the diagnostic criteria for PTSD compared with 2.2% of control patients. In multivariate analysis, MTBI was a predictor of PTSD (odds ratio, 4.47; 95% CI, 2.38-8.40) but not of PCS (odds ratio, 1.13; 95% CI, 0.82-1.55). Correspondence analysis suggested that symptoms considered part of PCS behave similarly to PTSD symptoms in the hyperarousal dimension. None of these 22 symptoms showed any pattern of clustering, and no clear proximity with head or nonhead injury status could be found. CONCLUSIONS AND RELEVANCE: Persistent subjective symptoms frequently reported 3 months after MTBI are not specific enough to be identified as a unique PCS and should be considered part of the hyperarousal dimension of PTSD.
Obesity is a major risk factor underlying the development of metabolic disease and a growing public health concern globally. Strategies to promote skeletal muscle metabolism can be effective to limit ...the progression of metabolic disease. Here, we demonstrate that the levels of the Hippo pathway transcriptional co-activator YAP are decreased in muscle biopsies from obese, insulin-resistant humans and mice. Targeted disruption of Yap in adult skeletal muscle resulted in incomplete oxidation of fatty acids and lipotoxicity. Integrated 'omics analysis from isolated adult muscle nuclei revealed that Yap regulates a transcriptional profile associated with metabolic substrate utilisation. In line with these findings, increasing Yap abundance in the striated muscle of obese (db/db) mice enhanced energy expenditure and attenuated adiposity. Our results demonstrate a vital role for Yap as a mediator of skeletal muscle metabolism. Strategies to enhance Yap activity in skeletal muscle warrant consideration as part of comprehensive approaches to treat metabolic disease.
Aims
To assess potential change in medicine exposure and association with the risk of road traffic crash across a time period that started before the implementation of a grading system warning of the ...effect of medicine on driving performance.
Methods
Data from three French national databases were extracted and matched: the national health care insurance database, police reports and the national police database of injurious crashes. Drivers involved in such crashes in France, from July 2005 to December 2011 and identified by their national identifier, were included. Association with the risk of crash was estimated using a case–control analysis comparing benzodiazepine and z‐hypnotic use among drivers responsible or not responsible for the crash.
Results
Totals of 69 353 responsible and 73 410 non‐responsible drivers involved in an injurious crash were included. Exposure to benzodiazepine anxiolytics was associated with an increased risk of being responsible for a road traffic crash during the pre‐intervention period (OR = 1.42 1.24–1.62). The association disappeared in the post‐intervention period, but became significant again thereafter. The risk of being responsible for a crash increased in users of z‐hypnotics across the study period.
Conclusions
Our results question the efficacy of the measures implemented to promote awareness about the effects of medicines on driving abilities. Prevention policies relating to the general driving population, but also to healthcare professionals, should be reviewed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
•The importance of receptor discovery for extracellular nucleotide signaling is critiqued.•How downstream signaling changes leading from receptor activation to growth changes is discussed.•The ...potential functions of apyrase enzymes in turning off the eATP signal and in regulating growth are evaluated.•The new phylogenetic and structural analyses of plant apyrases are provided.•The relationship of apyrases and eATP signaling to biotic and abiotic stress responses is documented and discussed.
Animal and plant cells release nucleotides into their extracellular matrix when touched, wounded, and when their plasma membranes are stretched during delivery of secretory vesicles and growth. These released nucleotides then function as signaling agents that induce rapid increases in the concentration of cytosolic calcium, nitric oxide and superoxide. These, in turn, are transduced into downstream physiological changes. These changes in plants include changes in the growth of diverse tissues, in gravitropism, and in the opening and closing of stomates. The concentration of extracellular nucleotides is controlled by various phosphatases, prominent among which are apyrases EC 3.6.1.5 (nucleoside triphosphate diphosphohydrolases, NTPDases). This review provides phylogenetic and pHMM analyses of plant apyrases as well as analysis of predicted post-translational modifications for Arabidopsis apyrases. This review also summarizes and discusses recent advances in research on the roles of apyrases and extracellular nucleotides in controlling plant growth and development. These include new findings that document how apyrases and extracellular nucleotides control auxin transport, modulate stomatal aperture, and mediate biotic and abiotic stress responses, and on how apyrase suppression leads to growth inhibition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The development of innovative antibacterial drugs against foodborne pathogens has led to an interest in novel materials such as nanomaterials. The unique features of nanomaterial qualify it for use ...as an antibacterial treatment. Noble metals and metal oxide nanoparticles, such as silver and magnetite nanoparticles, have been shown to be effective antibacterial medications against a range of microorganisms. In this work, Ag@Fe
3
O
4
-NPs were fabricated by using a wet chemical reduction and modified co-precipitation techniques. The antibacterial efficiency of the Ag/Fe
3
O
4
core shell nanoparticles was investigated by applying various techniques, such as the Kirby–Bauer Disk Diffusion test, minimum inhibitory concentration (MIC) and bactericidal concentration (MBC), Colony Forming Unit (CFU), and kill time assay. The toxicity mechanism of Ag@Fe
3
O
4
-NPs against
Salmonella typhimurium
and
Escherichia coli
was studied by apoptosis and reactive oxygen species (ROS) assays. The data revealed that a cubic core was surrounded by a silver shell, which indicated the regular morphology of silver magnetite core shell nanoparticles without any aggregation. Furthermore, Ag@Fe
3
O
4
-NPs is more toxic against
S. typhimurium
and
E. coli
than Ag-NPs and Fe
3
O
4
NPs. The MIC values for Ag/Fe
3
O
4
NPs against
S. typhimurium and E. coli
were 3.1 and 5.4 μg/ml, respectively, whereas the MIC values for Ag-NPs and MNPs against
S. typhimurium
and
E. coli
were 4.1 and 8.2 μg/ml for Ag-NPs and 6.9 and 10.3 μg/ml for MNPs. The results showed the ability of Ag@Fe
3
O
4
-NPs to induce apoptosis by generating ROS. Also, the ability of Ag@Fe
3
O
4
-NPs to liberate free Ag
+
and generate ROS
via
the Haber-Weiss cycle may be a plausible mechanism to explain the toxicity of Ag@Fe
3
O
4
-NPs - NPs.
While some medicinal drugs have been found to affect driving ability, no study has investigated whether a relationship exists between these medicines and crashes involving pedestrians. The aim of ...this study was to explore the association between the use of medicinal drugs and the risk of being involved in a road traffic crash as a pedestrian.
Data from 3 French nationwide databases were matched. We used the case-crossover design to control for time-invariant factors by using each case as its own control. To perform multivariable analysis and limit false-positive results, we implemented a bootstrap version of Lasso. To avoid the effect of unmeasured time-varying factors, we varied the length of the washout period from 30 to 119 days before the crash. The matching procedure led to the inclusion of 16,458 pedestrians involved in an injurious road traffic crash from 1 July 2005 to 31 December 2011. We found 48 medicine classes with a positive association with the risk of crash, with median odds ratios ranging from 1.12 to 2.98. Among these, benzodiazepines and benzodiazepine-related drugs, antihistamines, and anti-inflammatory and antirheumatic drugs were among the 10 medicines most consumed by the 16,458 pedestrians. Study limitations included slight overrepresentation of pedestrians injured in more severe crashes, lack of information about self-medication and the use of over-the-counter drugs, and lack of data on amount of walking.
Therapeutic classes already identified as impacting the ability to drive, such as benzodiazepines and antihistamines, are also associated with an increased risk of pedestrians being involved in a road traffic crash. This study on pedestrians highlights the necessity of improving awareness of the effect of these medicines on this category of road user.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pulmonary vascular leakage occurs early in acute respiratory distress syndrome (ARDS). Mortality is high (35-45%), but no effective pharmacotherapy exists. Production of anti-inflammatory adenosine ...by ecto-5'-nucleotidase (CD73) helps maintain endothelial barrier function. We tested whether interferon-beta-1a (IFN-beta-1a), which increases CD73 synthesis, can reduce vascular leakage and mortality in patients with ARDS.
In ex-vivo studies, we first established that IFN-beta-1a induced CD73 up-regulation in cultured human lung tissue samples. We then tested the safety, tolerability, and efficacy of intravenous human recombinant IFN-beta-1a (FP-1201) in patients with ARDS in an open-label study (comprising dose-escalation and expansion phases). We recruited patients from eight intensive care units in the UK. Eligible patients were aged 18 years or older, had ARDS, and were being treated with assisted ventilation. We established an optimal tolerated dose (OTD) in the first, dose-escalation phase. Once established, we gave all subsequently enrolled patients the OTD of intravenous FP-1201 for 6 days. We assessed 28-day mortality (our primary endpoint) in all patients receiving the OTD versus 28-day mortality in a group of patients who did not receive treatment (this control group comprised patients in the study but who did not receive treatment because they were screened during the safety windows after dose escalation). This trial is registered with ClinicalTrials.gov, number NCT00789685, and the EU Clinical Trials Register EudraCT, number 2008-000140-13.
IFN-beta-1a increased the number of CD73-positive vessels in lung culture by four times on day 1 (p=0·04) and by 14·3 times by day 4 (p=0·004). For the clinical trial, between Feb 23, 2009, and April 7, 2011, we identified 150 patients, of whom 37 were enrolled into the trial and given treatment. The control group consisted of 59 patients who were recruited to take part in the study, but who did not receive treatment. Demographic characteristics and severity of illness did not differ between treatment and control groups. The optimal tolerated FP-1201 dose was 10 μg per day for 6 days. By day 28, 3 (8%) of 37 patients in the treatment cohort and 19 (32%) of 59 patients in the control cohort had died-thus, treatment with FP-1201 was associated with an 81% reduction in odds of 28-day mortality (odds ratio 0·19 95% CI 0·03-0·72; p=0·01).
FP-1201 up-regulates human lung CD73 expression, and is associated with a reduction in 28-day mortality in patients with ARDS. Our findings need to be substantiated in large, prospective randomised trials, but suggest that FP-1201 could be the first effective, mechanistically targeted, disease-specific pharmacotherapy for patients with ARDS.
SARS-CoV-2 requires acidic pH to infect cells Kreutzberger, Alex J. B.; Sanyal, Anwesha; Saminathan, Anand ...
Proceedings of the National Academy of Sciences - PNAS,
09/2022, Volume:
119, Issue:
38
Journal Article
Peer reviewed
Open access
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry starts with membrane attachment and ends with spike (S) protein–catalyzed membrane fusion depending on two cleavage steps, ...namely, one usually by furin in producing cells and the second by TMPRSS2 on target cells. Endosomal cathepsins can carry out both. Using real-time three-dimensional single-virion tracking, we show that fusion and genome penetration require virion exposure to an acidic milieu of pH 6.2 to 6.8, even when furin and TMPRSS2 cleavages have occurred. We detect the sequential steps of S1-fragment dissociation, fusion, and content release from the cell surface in TMPRRS2-overexpressing cells only when exposed to acidic pH. We define a key role of an acidic environment for successful infection, found in endosomal compartments and at the surface of TMPRSS2-expressing cells in the acidic milieu of the nasal cavity.
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