Synthesis,Antimicrobial Activity and Molecular Docking Study of Novel α‐(Diphenylphosphoryl)‐ and α‐(Diphenylphosphorothioyl)cycloalkanone Oximes

A series of novel α‐(diphenylphosphoryl)‐ and α‐(diphenylphosphorothioyl)cycloalkanone oximes have been synthesized in search for novel bioactive molecules. Their structures were characterized by various spectroscopic methods including IR, NMR (¹H, ³¹P, ¹³C), mass spectrometry and single crystal X‐ray diffraction. The newly synthesized phosphorus‐containing oximes were screened for their in vitro antimicrobial activity against Gram‐positive bacteria (Staphylococcus aureus and Bacillus subtilis), Gram‐negative bacteria (Escherichia coli and Salmonella typhimurium) and fungal strains (Candida albicans and Candida glabrata). The biological assays showed that all the studied compounds exhibited high antibacterial and antifungal activities at only 0.1–2.1 μg/mL. In silico molecular docking studies in FabH enzyme active site were performed in order to predict the possible interaction modes and binding energies of the drug candidates at the molecular level.     

Chitinozoan zonation of the Late Ordovician and the Early Silurian of the island of Anticosti, Québec, Canada

A reappraisal of chitinozoan distribution across the Ordovician-Silurian boundary on the Island of Anticosti has led to the recognition of a new zone, the Ancyrochitina ellisbayensis biozone, in the uppermost part of the Ellis Bay Formation. This biozone lies between the well defined Upper Ordovician Spinachitina taugourdeaui biozone and the lowest Silurian (Rhuddanian) Plectochitina nodifera biozone of the Becscie Formation. The occurrence of such diagnostic species as P. nodifera, Belonechitina postrobusta, Conochitina electa and Ancyrochitina ramosaspina in the Lower Silurian of Anticosti points to a close similarity to faunas in Estonia and north Latvia and indicates an age ranging from the Parakidograptus acuminatus to the Coronograptus cyphus in terms of graptolite zones. The chitinozoan biozonation harmonizes with that based on conodonts and, to a lesser extent, with the known graptolite faunal succession. Five new species: Ancyrochitina ellisbayensis sp. nov., Clathrochitina postconcinna sp. nov., Conochitina gunriveris sp. nov., Clathrochitina perexilis sp. nov., Bursachitina basiconcava sp. nov. and three species in open nomenclature are described.     

Upper Ordovician and Lower Silurian chitinozoans from central Nevada and Arctic Canada

Late Ordovician and Early Silurian chitinozoans from the uppermost Vinini Formation, and the Hanson Creek Formation in central Nevada and the lower Cape Phillips Formation, Cape Manning section, in Arctic Canada have been re-investigated and a new chitinozoan biozonation is proposed. The Upper Ordovician of central Nevada can easily be correlated to that of Arctic Canada through the common occurrence of the Ordochitina nevadensis biozone in both regions. No such correlation, however, is possible with the Late Ordovician of Anticosti Island in eastern Canada because of the absence of the index Upper Ordovician chitinozoan zonal species of central Nevada such as Belonechitina tenuispinata sp. nov, Ordochitina nevadensis sp. nov. and Nevadachitina vininica gen. nov., sp. nov. in the former area.One new genus, Nevadachitina, and nine new species, Eisenackitina ripae, Belonechitina martinica, Nevadachitina vininica, Nevadachitina praevininica, Ordochitina nevadensis, Belonechitina tenuispinata, Belonechitina parvispinata, Tanuchitina laurentiana, Angochitina hansonica are described and illustrated in this paper and four species are left in open nomenclature.     

Rural and urban distribution of wild and domestic carnivore stools in the context of Echinococcus multilocularis environmental exposure

In zoonotic infections, the relationships between animals and humans lead to parasitic disease with severity that ranges from mild symptoms to life-threatening conditions. In cities and their surrounding areas, this statement is truer with the overcrowding of the protagonists of the parasites’ life cycle. The present study aims to investigate the distribution of a parasite, Echinococcus multilocularis, which is the causative agent of alveolar echinococcosis, using copro-sampling in historically endemic rural settlements of the eastern part of France and in newly endemic areas including urban parks and settlements surrounding Paris. Based on 2741 morphologically identified and geolocalized copro-samples, the density of fox faeces was generally higher in the surrounding settlements, except for one rural area where the faeces were at larger density downtown in the winter. Fox faeces are rare but present in urban parks. Dog faeces are concentrated in the park entrances and in the centre of the settlements. DNA was extracted for 1530 samples that were collected and identified from fox, dog, cat, stone marten and badger carnivore hosts. Echinococcus multilocularis diagnosis and host faecal tests were performed using real-time PCR. We failed to detect the parasite in the surroundings of Paris, but the parasite was found in the foxes, dogs and cats in the rural settlements and their surroundings in the historically endemic area. A spatial structuring of the carnivore stool distribution was highlighted in the present study with high densities of carnivore stools among human occupied areas within some potentially high-risk locations.     

Mutually exclusive distribution of the sap and eag S-layer genes and the lytB/lytA cell wall hydrolase genes in Bacillus thuringiensis

Recently, two Bacillus thuringiensis strains were reported to synthesize parasporal inclusion bodies made not of the expected crystal (Cry) proteins but rather of the surface layer proteins (SLP) Sap (encoded by sap) and EA1 (encoded by eag), respectively. Whether the presence of the sap and eag genes is restricted to these two B. thuringiensis strains or ubiquitous in B. thuringiensis is unknown. We report here the distribution of the sap and eag genes in B. thuringiensis. Strains in the Bacillus cereus group were added for comparison purposes. We show that sap and eag are either present in tandem in 35% of the B. thuringiensis strains analysed and absent in 65% of the strains. When absent, a different tandem, the lytB/lytA cell wall hydrolase genes, is present. The distribution of the sap and eag S-layer and the lytB/lytA cell wall hydrolase genes is not species-specific in B. thuringiensis, B. cereus and Bacillus weihenstephanensis. Bacillus anthracis and Bacillus mycoides harbor sap and eag but not lytB/lytA. The sap, eag and lytB/lytA genes were absent in Bacillus pseudomycoides. Clearly, the distribution of the sap and eag S-layer and the lytB/lytA cell wall hydrolase genes in B. thuringiensis and in the Bacillus cereus group is mutually exclusive. We also showed that two genes involved in cell wall metabolism, csaA and csaB, are present not only upstream of the sap and eag S-layer genes, but also upstream of the lytB/lytA tandem in strains where sap and eag are absent. Bootstrapped neighbor-joining trees were inferred from the translated amino acid sequences of sap, eag and the tandem lytB/lytA, respectively.     

Self-harm and risk of motor vehicle crashes among young drivers: findings from the DRIVE Study

Background

Some motor vehicle crashes, particularly single-vehicle crashes, may result from intentional self-harm. We conducted a prospective cohort study to assess the risk that intentional self-harm poses for motor vehicle crashes among young drivers.

Methods

We prospectively linked survey data from newly licensed drivers aged 17–24 years to data on licensing attempts and police-reported motor vehicle crashes during the follow-up period. We investigated the role of recent engagement in self-harm on the risk of a crash. We took into account potential confounders, including number of hours of driving per week, psychological symptoms and substance abuse.

Results

We included 18 871 drivers who participated in the DRIVE Study for whom data on self-harm and motor vehicle crashes were available. The mean follow-up was 2 years. Overall, 1495 drivers had 1 or more crashes during the follow-up period. A total of 871 drivers (4.6%) reported that they had engaged in self-harm in the year before the survey. These drivers were at significantly increased risk of a motor vehicle crash compared with drivers who reported no self-harm (relative risk [RR] 1.42, 95% confidence interval [CI] 1.15–1.76). The risk remained significant, even after adjustment for age, sex, average hours of driving per week, previous crash, psychological distress, duration of sleep, risky driving behaviour, substance use, remoteness of residence and socio-economic status (RR 1.37, 95% CI 1.09–1.72). Most of the drivers who reported self-harm and had a subsequent crash were involved in a multiple-vehicle crash (84.1% [74/88]).

Interpretation

Engagement in self-harm behaviour was an independent risk factor for subsequent motor vehicle crash among young drivers, with most crashes involving multiple vehicles.Globally, poor mental health and injuries (including suicide) are ranked as the first and second highest contributors of lost disability-adjusted life-years among young people.¹ Self-harm and suicide attempts are reported by 5%–17% of people aged 14–25 years and may be increasing in prevalence.^2–5 Self-harm refers to the deliberate injuring of oneself through such methods as superficial cutting, attempted hanging and poisoning.⁶ Self-harm is performed most often by people with mental health problems and is a risk factor for suicide and other causes of death.^6–8 Reasons for this behaviour are not well known. They may include coping with feelings of distress, suicidal intent, crying out for attention, addictive self-mutilation, impulsive behaviour, self-loathing and punishment, and attempting to feel in control. A recent study found the rate ratio of self-harm to suicide to be 36 (95% confidence interval [CI] 34.9–37.1).⁹The rate of death from motor vehicle crashes is hypothesized to be increased among individuals who have previously attempted suicide, and crashes are implicated as a mode of self-harm.^8,10,11 There are several possible reasons for this increased risk of crash-related injury and death. For example, individuals who self-harm may deliberately attempt to injure or kill themselves using a motor vehicle. Alternatively, an increased risk of crash may occur through an indirect association of self-harm with other risk factors associated with crashes. Poor mental health for example is associated with self-harm and has been linked to higher rates of crashes.⁸ Common symptoms of poor mental health include depressed or anxious mood, disturbed sleep and poor concentration, all of which may impair cognitive and psychomotor function and thereby impair a person’s ability to drive.¹² Self-harm is also commonly associated with alcohol and other substance use, which are also risk factors for motor vehicle crashes.^2,13,14 Finally, developmentally young adults and people who self-harm have poor impulse control, which suggests that they may be particularly vulnerable to a range of health risks, including accidental injury.^6,15,16Most studies of motor vehicle crashes among people who self-harm recruited patients seeking health services and used linked data from death registers to examine fatal outcomes. We conducted a prospective study to examine self-harm as a risk factor for nonfatal motor vehicle crashes. We used a cohort of young drivers of whom a subset engaged in self-harm. We also explored the role of associated risk factors, including symptoms of mental disorder and substance use, in explaining any difference in rates of crash.     

Idiopathic scrotal calcinosis: a non-elucidated pathogenesis and its surgical treatment

Scrotal calcinosis (SC) is a rare, benign entity defined as the presence of multiple calcified nodules within the scrotal skin. In most cases, there are no associated symptoms. We report the case of 27-year-old man with a massive SC. Treatment was surgical with complete excision of the affected part of the scrotum wall. Histopathologically, there was no epithelial lining around the calcified nodules and no cystic structure. Therefore, our case was considered idiopathic SC.     

Discrimination Between Mesophilic and Psychrotolerant Strains in the Bacillus cereus Group Based on the PstI Digestion of the pycA Gene

A simple and rapid assay for the detection of Bacillus weihenstephanensis isolates and other psychrotolerant strains in the Bacillus cereus group was developed. It is based on the presence of a nucleotide substitution at position 795 on the housekeeping pycA gene in all B. weihenstephanensis strains. This mutation creates a PstI recognition site. It is absent in mesophilic strains in the B. cereus group. The pycA gene is amplified by PCR and the amplicons submitted to PstI digestions. In mesophilic strains, a single band of 1,718 bp in length is visualised on an agarose gel. In B. weihenstephanensis strains and in all other psychrotolerant strains from the B. cereus group, the amplicons are cleaved and two bands of 1,175 and 543 bp, respectively, are visualised. This method could be used for the screening of B. cereus collections and for the identification of psychrotolerant and mesophilic isolates from different environments.     

Flagellin (FliC) protein sequence diversity among <Emphasis Type="Italic">Bacillus thuringiensis</Emphasis> does not correlate with H serotype diversity

In Escherichia coli, the fliC gene encodes flagellin, the protein responsible for eliciting the immunological reaction in H serotyping. Here, the presence of the flagellin fliC gene was studied in 86 Bacillus thuringiensis strains encompassing 67 H serotypes. Nineteen strains from four additional species in the B. cereus sensu lato group, B. cereus, B. anthracis, B. mycoides, and B. weihenstephanensis, were added for comparison purposes. The fliC genes were amplified, cloned and their nucleotide sequences determined and translated into amino acid sequences. A bootstrapped neighbor-joining tree was generated from the alignment of the translated amino acid sequences of the amplicons. Although most B. thuringiensis H serotypes had different flagellin amino acid sequences, some different B. thuringiensis serovars shared identical flagellin amino acid sequences. In addition, although serovars from the same H serotype were sometimes found clustered together, several serovars from the same H serotype carried flagellins with sufficiently different amino acid sequences as to be located on distant clusters. No correlations could be established between flagellin (FliC) protein sequence diversity among B. thuringiensis H serotypes and H serotype diversity. These suggest that the B. thuringiensis fliC gene does not code for the flagellin copy responsible for eliciting the immunological reaction in H serotyping. In a previous study, the authors have shown that the B. thuringiensis hag gene codes for the flagellin copy responsible for eliciting the immunological reaction in H serotyping. It is proposed that the B. thuringiensis fliC gene studied here be renamed and that the so-called hag gene studied before be renamed fliC, both in accordance with the E. coli nomenclature. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.