Engberghermann0511
Animals exposed to 14 days of CUELS showed an opposite anxious phenotype compared to 3 and 7 days of CUELS. No significant changes were observed in memory and cognition, social behavior and cortisol levels. In general, 7 days of CUELS protocol decreased anxiety in young and adult zebrafish, and could be used to understand the mechanisms underlying early-life experiences-derived alterations in neural circuits of anxiety.Despite high prevalence, medical impact and societal burden, anxiety, depression and other affective disorders remain poorly understood and treated. Clinical complexity and polygenic nature complicate their analyses, often revealing genetic overlap and cross-disorder heritability. However, the interplay or overlaps between disordered phenotypes can also be based on shared molecular pathways and 'crosstalk' mechanisms, which themselves may be genetically determined. We have earlier predicted (Kalueff et al., 2014) a new class of 'interlinking' brain genes that do not affect the disordered phenotypes per se, but can instead specifically determine their interrelatedness. To test this hypothesis experimentally, here we applied a well-established rodent chronic social defeat stress model, known to progress in C57BL/6J mice from the Anxiety-like stage on Day 10 to Depression-like stage on Day 20. The present study analyzed mouse whole-genome expression in the prefrontal cortex and hippocampus during the Day 10, thegenesis and, hence, determine the progression from one pathological state to another. This concept can potentially be extended to other brain conditions as well. This preclinical study also further implicates cilial and astrocytal mechanisms in the pathogenesis of affective disorders.
Patients with remitted major depressive disorder (rMDD) generally rely on maladaptive coping strategies for stressful situations. These maladaptive copings are associated with an elevated relapse risk of rMDD; however, their neural basis remains poorly understood.
We enrolled (1) 45 patients with rMDD (17-item Hamilton Depression Rating Scale [HRSD
] total score≤3) and (2) 56 healthy controls (HCs). Coping styles were measured using the Coping Inventory for Stressful Situations (CISS) according to three coping dimensions avoidance-, emotion-, and task-oriented copings. Trichostatin A The cognitive strategic processes of the prefrontal cortex were measured using a verbal fluency task (VFT). Furthermore, regional frontotemporal hemodynamic responses were monitored by near-infrared spectroscopy (NIRS).
Patients with rMDD had significantly lower task-oriented coping scores and significantly higher avoidance- and emotion-oriented coping scores than HCs. Predominantly in the left frontotemporal region, patients with rMDD had lower frontotemporal hemodynamic responses during a VFT than HCs. Hemodynamic responses in the right inferior frontal gyrus of patients with rMDD were significantly and negatively associated with avoidance-oriented coping scores, but not of HCs. Conversely, those responses of HCs were significantly and positively associated with task-oriented coping scores, but not of patients with rMDD.
Alteration in the right inferior frontal cortex plays an important role in dysfunction to stress response in patients with rMDD. Differential functioning patterns of the right inferior frontal cortex associated with coping strategies may link to MDD recurrence vulnerability.
Alteration in the right inferior frontal cortex plays an important role in dysfunction to stress response in patients with rMDD. Differential functioning patterns of the right inferior frontal cortex associated with coping strategies may link to MDD recurrence vulnerability.
In the context of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the supply of personal protective equipment remains under severe strain. To address this issue, re-use of surgical face masks and filtering facepiece respirators has been recommended; prior decontamination is paramount to their re-use.
We aim to provide information on the effects of three decontamination procedures on porcine respiratory coronavirus (PRCV)-contaminated masks and respirators, presenting a stable model for infectious coronavirus decontamination of these typically single-use-only products.
Surgical masks and filtering facepiece respirator coupons and straps were inoculated with infectious PRCV and submitted to three decontamination treatments, ultraviolet (UV) irradiation, vaporized H
O
, and dry heat treatment. Viruses were recovered from sample materials and viral titres were measured in swine testicle cells.
UV irradiation, vaporized H
O
and dry heat reduced infectious PRCV by mormore than three orders of magnitude of an infectious coronavirus in line with the United States Food and Drug Administration policy regarding face masks and respirators. It presents advantages of uncomplicated manipulation and utilization in a BSL2 facility, therefore being easily adaptable to other respirator and mask types.
Heater-cooler units (HCUs) used during cardiopulmonary bypass may become colonized with non-tuberculous mycobacteria (NTM), including Mycobacterium chimaera. Recently, a worldwide investigation conducted in hospitalized infected patients has detected M.chimaera in several Stockert 3T HCUs manufactured by LivaNova.
Microbiological surveillance on Stockert 3T (LivaNova) and Maquet HCU40 (Getinge) devices as well as an evaluation of the efficacy of their recommended decontamination protocols.
A total of 308 water samples were collected from 29 HCUs 264 samples were collected from 17 Stockert 3T HCUs and 44 samples from 12 Maquet HCU40 devices. Samples were tested for total viable counts (TVCs) at both 22 and 36°C, Pseudomonas aeruginosa, coliform bacteria, and NTM. The microbiological surveillance began in June 2017 and ran until October 2019.
A total of 308 HCU water samples were analysed, 65.5% of which yielded NTM. The most frequently colonized device with NTM was the Stockert 3T (88.2%), with a frequisk of NTM contamination is to closely monitor the water quality in the HCU, keep it as clean as possible, and treat it like any other biohazardous material.The phospholipase A2 (PLA2) inhibitors varespladib (LY315920) and its orally available derivative methyl-varespladib (LY333013) have been proposed as potential therapies for the treatment of snakebite envenomings in which toxicity depends on the action of PLA2s. In this study, the ability of LY315920 to abrogate the effect of the potent neurotoxic venom of Oxyuranus scutellatus (taipan) was assessed using the mouse phrenic nerve-diaphragm preparation. LY315920 inhibited the venom when (a) incubated with venom before addition to the medium; (b) added to the medium before addition of venom, and; (c) added to the medium within 30 min after addition of venom, and even after the onset of decline in twitch response. This contrasts with previous results with antivenom using the same experimental model, in which the window of time when antibodies are effective is shorter than 10 min. It is proposed that such differences may depend either on the higher affinity of the inhibitor for PLA2s or on the possibility that LY315920 reaches the cytosol of the nerve terminals, inhibiting neurotoxins that have been internalized. Our findings bear implications on the therapeutic potential of varespladib in neurotoxic snakebite envenomings mediated by presynaptically-acting PLA2s.Tetanus is an acute, fatal disease caused by exotoxin produced by Clostridium tetani. The current vaccine against tetanus is based on inactivated tetanus toxin (TeNT). To develop a recombinant TeNT vaccine suitable for replacement of full-length tetanus toxoid (TT) vaccine for use in humans, a recombinant non-tagged isoform of the Hc domain of the tetanus toxin (THc) was expressed in Escherichia coli and purified by sequential chromatography steps. The immunogenicity and protective effect of the THc antigen were explored and compared with those of TT in Balb/c mice. The THc-based subunit vaccine provided complete protection against TeNT challenge following a high dosage as a toxoid vaccine. While the anti-THc and neutralising antibody titres were higher for the THc-based vaccine than the TT vaccine because protective epitopes are located on the THc domain. Frequency- and dose-dependent immunoprotection were also observed in THc-immunised mice. Mice immunised with one injection of 1 μg or 4 μg THc antigen were completely protected against 102 or 103 50% mouse lethal dose (LD50) of TeNT, respectively. Furthermore, the THc protein was found to recognise and bind to ganglioside GT1b in a dose-dependent manner, and anti-THc sera antibodies also inhibited binding between THc and GT1b. Antigen on the form of recombinant non-tagged THc domain expressed in E. coli achieved strong immunoprotective potency, suggesting that it could be developed into a candidate subunit vaccine against tetanus as an alternative to the current TT vaccine.Acetylcholine binding proteins (AChBPs), structural and functional surrogates of the extracellular binding domain of nicotinic acetylcholine receptor (nAChRs), in complex with various antagonists and agonists have provided detailed insights into the neurotransmitter binding site of nAChRs. The classical long-chain α-neurotoxins bungarotoxin (44-fold) and cobratoxin (7-fold) bind to Lymnaea stagnalis (Ls)-AChBP with higher affinity compared to Aplysia californica (Ac)-AChBP. In this study, we describe a novel long chain α-neurotoxin Drysdalin, which has higher binding affinity (7-fold) to Ac-AChBP when compared to Ls-AChBP. This suggests an involvement of different regions or modes of interaction of drysdalin, when compared to the bungarotoxin and cobratoxin. We also found that the C-terminal 24-amino acid residues of drysdalin are critical for the binding to Ac-AChBP and its removal caused ~90-fold reduction in affinity. Further to understand the interaction of drysdalin with Ac-AChBP, we studied the role of three non-conserved amino acid residues of drysdalin, namely Arg30, Leu34 and Ala37. Substitution of Arg30 with the conserved Phe residue caused a ~100-fold reduction, Leu34 with conserved Arg caused a ~6-fold reduction, whereas substitution of Ala37 with conserved Arg enhanced the binding by 3-fold. The dramatic influence of this carboxyl terminal sequence enriched in arginine and proline residues suggests that the toxin binding pose is influenced primarily by this extended sequence.Ochratoxins (OTs) are a group of mycotoxins produced by Aspergillus and Penicillium spp. which are ubiquitous. They infect the crops during pre- and post-harvest conditions and contaminate various food and feed. Among all the OTs produced, ochratoxin A (OTA) poses serious health issues like neurotoxicity and carcinogenesis. The harmful impact of the toxins is observed in both humans and animals. The toxins get accumulated in the organs of animals through the contaminated animal-feed which further contaminate the products derived from them, such as milk and meat-based products. Therefore, sensitive and robust identification, detection, and quantification methods along with efficient management and control measures are crucial. Spectrometric and spectroscopy techniques are quite sensitive and lead to better detection of the toxin in the food products. Control and preventive measures during harvesting, storage and transportation are found to be effective in managing the production of such toxins. This review insight on the occurrence, chemistry, biosynthesis, effects on human health and agriculture, detections, management, and control strategies of ochratoxins.
