Experiences of Mental Distress during COVID-19: Thematic Analysis of Discussion Forum Posts for Anxiety, Depression, and Obsessive-Compulsive Disorder.

The psychological impact of the COVID-19 pandemic on coronavirus patients, health care workers, and the general population is clear. Relatively few studies have, however, considered the impact of the pandemic on those with pre-existing mental health conditions. Therefore, the present study investigates the personal experiences of those with anxiety, depression, and obsessive-compulsive disorder during COVID-19. We conducted a qualitative study utilising Reddit discussion forum posts. We conducted three separate thematic analyses from 130 posts in subreddit forums aimed for people identifying with anxiety, depression, and obsessive-compulsive disorder. We identified a number of similar discussion forum themes (e.g., COVID-19 intensifying symptoms and a lack of social support), as well as themes that were unique to each forum type (e.g., hyperawareness and positive experiences during the pandemic). Findings should guide future practice and the support provided to those living with mental distress.

A large multicenter cohort on the use of full-thickness resection device for difficult colonic lesions.

BACKGROUND: Introduction of the full-thickness resection device (FTRD) has allowed endoscopic resection of difficult lesions such as those with deep wall origin/infiltration or those located in difficult anatomic locations. The aim of this study is to assess the outcomes of the FTRD among its early users in the USA. METHODS: Patients who underwent endoscopic full-thickness resection (EFTR) for lower gastrointestinal tract lesions using the FTRD at 26 US tertiary care centers between 10/2017 and 12/2018 were included. Primary outcome was R0 resection rate. Secondary outcomes included rate of technical success (en bloc resection), achievement of histologic full-thickness resection (FTR), and adverse events (AE). RESULTS: A total of 95 patients (mean age 65.5 ± 12.6 year, 38.9% F) were included. The most common indication, for use of FTRD, was resection of difficult adenomas (non-lifting, recurrent, residual, or involving appendiceal orifice/diverticular opening) (66.3%), followed by adenocarcinomas (22.1%), and subepithelial tumors (SET) (11.6%). Lesions were located in the proximal colon (61.1%), distal colon (18.9%), or rectum (20%). Mean lesion diameter was 15.5 ± 6.4 mm and 61.1% had a prior resection attempt. The mean total procedure time was 59.7 ± 31.8 min. R0 resection was achieved in 82.7% while technical success was achieved in 84.2%. Histologically FTR was demonstrated in 88.1% of patients. There were five clinical AE (5.3%) with 2 (2.1%) requiring surgical intervention. CONCLUSIONS: Results from this first US multicenter study suggest that EFTR with the FTRD is a technically feasible, safe, and effective technique for resecting difficult colonic lesions.

Impacting on factors promoting intra-group aggression in secure psychiatric settings.

Three preliminary and linked studies investigate the impact of making alterations to factors considered relevant to engaging in and experiencing intra-group aggression (bullying) among adult male patients detained in a single secure forensic hospital. Study one (n = 44) outlines the institutional factors, attitudes towards bullying and environmental factors that increase the likelihood of engaging in bullying and/or being victimised. Study two (n = 53 patients and 167 staff) assesses the effect of three variations of intervention that aimed to reduce intra-group aggression through direct alteration of the physical and psychosocial environment, using data from both patients and staff. Study three (n = 414) looks at the effects of two variations of the intervention used in study two, which offered patients' participation in individual and communal activities. It was predicted that changes to the physical and social environment would produce a reduction in the factors shown to predict intra-group aggression. Attitudes supportive of bullying and the presence of social hierarchies each increased the likelihood of engaging in bullying. Indirect changes to the social environment on the wards had more positive effects than those incorporating direct alterations to the physical and social environment. The differences in effectiveness of the two approaches are discussed in relation to the established predictors of intra-group aggression. The research concludes by noting the preliminary nature of the research and outlining potential directions for future research and intervention.

Behavioural responses of stable flies to cattle manure slurry associated odourants.

Stable flies (Stomoxys calcitrans [Diptera: Muscidae] L.) are blood-feeding synanthropic pests, which cause significant economic losses in livestock. Stable fly antennae contain olfactory sensilla responsive to host and host environment-associated odours. Field observation indicated that the abundance of stable flies increased significantly in grasslands or crop fields when cattle manure slurry was applied. Major volatile compounds emanating from manure slurry were collected and identified. Behavioural responses of stable flies to those compounds were investigated in laboratory bioassays and field-trapping studies. Results from olfactometer assays revealed that phenol, p-cresol and m-cresol were attractive to adult stable flies. When tested individually, attraction was higher with lower dosages. Stable flies were most attracted to blends of phenol and m-cresol or p-cresol. Traps with binary blend lures caught more stable flies in field trials as well.

Interleukin-17 enhances immunosuppression by mesenchymal stem cells.

IL-17 is one of the most potent and most actively investigated proinflammatory cytokines. In this study, we examined the effect of IL-17 on mesenchymal stem cells (MSCs) under the influence of inflammatory cytokines. Ironically, IL-17 dramatically enhanced the immunosuppressive effect of MSCs induced by IFNγ and TNFα, revealing a novel role of IL-17 in immunosuppression. Interestingly, we found that this action of IL-17 was dependent on the promoted expression of a key immune suppressive molecule, inducible nitric oxide synthase (iNOS), in MSCs. In a concanavalin A (ConA)-induced hepatitis mouse model, we found that IL-17 also enhanced the in vivo immunosuppressive effect of MSCs in an iNOS-dependent manner. Moreover, this promoting effect of IL-17 was found to be exerted through enhancing mRNA stability by modulating the protein level of ARE/poly(U)-binding/degradation factor 1 (AUF1), a well-known factor that promotes mRNA decay. In auf1(-/-) MSCs, IFNγ and TNFα could induce maximal immunosuppressive effect, both in vitro and in vivo, without the need for IL-17. Thus, our studies demonstrated that in the presence of MSCs, IL-17 promotes immunosuppression.

Nepetalactones from essential oil of Nepeta cataria represent a stable fly feeding and oviposition repellent.

The stable fly, Stomoxys calcitrans (L.) (Diptera: Muscidae), is one of the most serious pests to livestock. It feeds mainly on cattle and causes significant economic losses in the cattle industry. Standard stable fly control involving insecticides and sanitation is usually costly and often has limited effectiveness. As we continue to evaluate and develop safer fly control strategies, the present study reports on the effectiveness of catnip (Nepeta cataria L.) oil and its constituent compounds, nepetalactones, as stable fly repellents. The essential oil of catnip reduced the feeding of stable flies by >96% in an in vitro bioassay system, compared with other sesquiterpene-rich plant oils (e.g. amyris and sandalwood). Catnip oil demonstrated strong repellency against stable flies relative to other chemicals for repelling biting insects, including isolongifolenone, 2-methylpiperidinyl-3-cyclohexen-1-carboxamide and (1S,2'S)-2-methylpiperidinyl-3-cyclohexen-1-carboxamide. The repellency against stable flies of the most commonly used mosquito repellent, DEET, was relatively low. In field trials, two formulations of catnip oil provided >95% protection and were effective for up to 6 h when tested on cattle. Catnip oil also acted as a strong oviposition repellent and reduced gravid stable fly oviposition by 98%.

Characterization of olfactory sensilla of Stomoxys calcitrans and electrophysiological responses to odorant compounds associated with hosts and oviposition media.

Stable flies, Stomoxys calcitrans L. (Diptera: Muscidae), are economically important biting flies that have caused billions of dollars in losses in the livestock industry. Field monitoring studies have indicated that olfaction plays an important role in host location. To further our understanding of stable fly olfaction, we examined the antennal morphology of adults using scanning electron microscopy techniques. Four major types of sensillum were found and classified as: (a) basiconic sensilla; (b) trichoid sensilla with three subtypes; (c) clavate sensilla, and (d) coeloconic sensilla. No significant differences between male and female flies in abundances (total numbers) of these sensillum types were observed, except for medium-sized trichoid sensilla. The distinctive pore structures found on the surface of basiconic and clavate sensilla suggest their olfactory functions. No wall pores were found in trichoid and coeloconic sensilla, which suggests that these two types of sensillum may function as mechano-receptors. Details of the distributions of different sensillum types located on the funicle of the fly antenna were also recorded. Electroantennogram results indicated significant antennal responses to host-associated compounds. The importance of stable fly olfaction relative to host and host environment seeking is discussed. This research provides valuable new information that will enhance future developments in integrated stable fly management.

Chronic network stimulation enhances evoked action potentials.

Neurons cultured on multielectrode arrays almost always lack external stimulation except during the acute experimental phase. We have investigated the effects of chronic stimulation during the course of development in cultured hippocampal neural networks by applying paired pulses at half of the electrodes for 0, 1 or 3 r/day for 8 days. Spike latencies increased from 4 to 16 ms as the distance from the stimulus increased from 200 to 1700 microm, suggesting an average of four synapses over this distance. Compared to no chronic stimulation, our results indicate that chronic stimulation increased evoked spike counts per stimulus by 50% at recording sites near the stimulating electrode and increased the instantaneous firing rate. On trials where both pulses elicited responses, spike count was 40-80% higher than when only one of the pulses elicited a response. In attempts to identify spike amplitude plasticity, we found mainly amplitude variation with different latencies suggesting recordings from neurons with different identities. These data suggest plastic network changes induced by chronic stimulation that enhance the reliability of information transmission and the efficiency of multisynaptic network communication.

Kissing as an evolutionary adaptation to protect against Human Cytomegalovirus-like teratogenesis.

Mouth to mouth sexual kissing is seen in more than 90% of human cultures. Various theories have been put forward to account for this but none offer a full explanation within an evolutionary framework. As mouth to mouth sexual kissing exposes each participant to the diseases of the other, it must confer significant benefit. Human Cytomegalovirus (HCMV) is a ubiquitous infection that carries a severe teratogenic risk if primary infection is acquired during certain critical periods. As HCMV is present in salivary gland epithelial cells and sheds from periodontitis induced lesions, female inoculation with a specific male's HCMV is most efficiently achieved through mouth to mouth contact and saliva exchange, particularly where the flow of saliva is from the male to the typically shorter female. The current hypothesis proposes that mouth to mouth sexual kissing enables females to control when they become infected with a particular male's HCMV and so protect their offspring from the threat of teratogenesis from primary infection during vulnerable times in their development. Females only gain this benefit if they also avoid becoming infected by other males. Hence HCMV induced teratogenesis is a strong viral pressure towards the development of monogamy as well as kissing as a behavioural strategy to protect against it.

Neuron network activity scales exponentially with synapse density.

Neuronal network output in the cortex as a function of synapse density during development has not been explicitly determined. Synaptic scaling in cortical brain networks seems to alter excitatory and inhibitory synaptic inputs to produce a representative rate of synaptic output. Here, we cultured rat hippocampal neurons over a three-week period to correlate synapse density with the increase in spontaneous spiking activity. We followed the network development as synapse formation and spike rate in two serum-free media optimized for either (a) neuron survival (Neurobasal/B27) or (b) spike rate (NbActiv4). We found that while synaptophysin synapse density increased linearly with development, spike rates increased exponentially in developing neuronal networks. Synaptic receptor components NR1, GluR1 and GABA-A also increase linearly but with more excitatory receptors than inhibitory. These results suggest that the brain's information processing capability gains more from increasing connectivity of the processing units than increasing processing units, much as Internet information flow increases much faster than the linear number of nodes and connections.

Pertussis toxin B-oligomer suppresses human immunodeficiency virus-1 Tat-induced neuronal apoptosis through feedback inhibition of phospholipase C-beta by protein kinase C.

Human immunodeficiency virus (HIV)-1 Tat is a multifunctional protein involved in viral replication, inflammation and apoptosis. Tat activates phospholipase C-beta (PLC-beta), presumably via a pertussis toxin (PTX) sensitive G(i) protein, which is critical for neuronal apoptosis. In this study, we show that Tat-mediated intracellular Ca(2+) release in rat pheochromocytoma (PC-12) cells and rat primary cortical neuronal cultures was abrogated by pretreatment with either pertussis toxin and/or its B-oligomer subunit (PTX-B), devoid of ADP ribosyltransferase activity. PTX-B pretreatment also inhibited intracellular Ca(2+) release by bradykinin and 2,4,6-trimethyl-N-(m-3-trifluoromethylphenyl) benzenesulfonamide (m-3M3FBS), a director activator of phospholipase C. Activation of protein kinase C (PKC) by phorbol 12,13-dibutyrate (PdBu) mimicked the PTX-B-mediated inhibition of m-3M3FBS-stimulated intracellular Ca(2+) increase, while inhibition of PKC by bisindolylmaleimide I hydrochloride (BIM) reversed the inhibitory action of PTX-B. Functionally, PTX-B reduced Tat-induced Bax and caspase-3 proteins and reduced cell apoptosis. We conclude that PTX inhibition of Tat-mediated intracellular Ca(2+) release is independent of ADP ribosylation of the G(i) protein via the A protomer, but mediated by the B-oligomer. Furthermore, PTX-B suppresses HIV-1 Tat-mediated apoptosis by reducing its activation of PLC-beta through a PKC activation pathway.

Dopamine and Abeta-induced stress signaling and decrements in Ca2+ buffering in primary neonatal hippocampal cells are antagonized by blueberry extract.

We have shown previously that dietary blueberry (BB) extract supplementation (S) reversed several parameters of neuronal and behavioral (e.g., cognition) aging in rodents. Additionally, findings indicate that COS-7 cells transfected with muscarinic receptor subtypes (e.g., M1) showed decrements in Ca;{2+} clearance following depolarization (Ca;{2+} Recovery time, Ca;{2+}RT) that were antagonized by BB. Since it has been postulated that at least part of the loss of cognitive function in aging may be dependent upon a dysregulation in calcium homeostasis (i.e., Ca;{2+}RT), we assessed whether: a) Ca;{2+}RT would be altered in dopamine (DA)- or amyloid beta (Abeta)-exposed cultured primary hippocampal neuronal cells (HNC), and b) BB pre-treatment of the cells would prevent these deficits. Thus, control or BB (0.5 mg/ml)-treated HNC were exposed to DA (0.1 mM, 2 hrs), Abeta(40) (25 microM, 24 hrs), Abeta(42) (25 microM, 24 hrs), and Abeta(25-35) (25 microM, 24 hrs), and Ca;{2+}RT following KCl-induced depolarization assessed. Ca;{2+}RT was assessed as the % of HNC showing recovery to 50%-70% of control at 5, 10, or 15 min after depolarization. Results indicated that DA significantly lowered Ca;{2+}RT in the HNC at all time points examined after depolarization. However, BB treatment selectively prevented these declines in Ca;{2+}RT. In the case of Abeta, the greatest effects on Ca;{2+}RT were seen when the hippocampal cells were Abeta(42)-treated. These effects were antagonized by BB treatment. Abeta(40) produced fewer deficits on Ca;{2+}RT than those seen when the HNC were pre-treated with either A;{2+}(42) or A;{2+}(25-35), but BB was relatively ineffective in antagonizing the deficits in Ca;{2+}RT produced by A;{2+}(40) or A;{2+}(25-35). Additional analyses indicated that BBs may be exerting their protective effects in the hippocampal cells by altering levels of phosphorylated MAPK, PKCgamma, and phosphorylated CREB. Therefore it appears that at least part of the protective effect of BBs may involve alterations in stress signaling.

Independence of synaptic specificity from neuritic guidance.

Neuronal circuits are interconnected with a high degree of specificity. While axonal guidance has been demonstrated to be crucial for the choice of the correct target region, its role in specificity at the level of individual cells remains unclear. Specificity of synapse formation may either result from precise guidance of axonal outgrowth onto the target or depend on a molecular "match" between pre- and postsynapse. To distinguish between these possibilities, an in vitro system was used in which neuritic outgrowth of rat cortical neurons is accurately guided along the narrow pathways of a surface micropattern. The micropattern consisted of a blend of extracellular matrix molecules applied to a cell repellent background of polystyrene by microcontact printing. The system reproduces guidance by attractant and repellent surface cues while no other signals that may influence synapse formation, like gradients of trophic factors or accumulations of signaling molecules, are provided. While the number of contact points between neighboring cells was strongly reduced on patterned substrates due to the geometrical restrictions, frequency of synapse formation was not different from homogeneous cultures. Thus it was unaffected by stringent guidance onto the target cell or by the number of cell-cell contacts. Moreover, a statistically significant enrichment of reciprocal contacts between mixed pairs of excitatory and inhibitory neurons over probabilistic predictions was found, which has similarly been shown by others in dissociated neuronal cultures. Our results indicate that precise axonal guidance is insufficient for target-specific synapse formation and suggest that instead recognition between individual cells is required.

Connectivity patterns in neuronal networks of experimentally defined geometry.

Experimental control over the position and connectivity pattern of neurons on a surface is of central interest for applications in biotechnology, such as cell-based biosensors and tissue engineering. By restricting neuronal networks to a simple grid pattern, a drastic reduction of network complexity can be achieved relative to networks on homogeneous substrates. Therefore, patterned neuronal networks are also a valuable tool in research on neuronal signal transduction. Microcontact printing has emerged as a simple and efficient method for surface patterning to direct cellular attachment. Although the formation of synaptic contacts in networks of rat cortical cells on such surfaces has been demonstrated, evidence of more complex circuits has been lacking. Triple patch-clamp measurements were performed to analyze connectivity in neuronal networks complying with a grid-shaped micropattern. Cells adhered stringently to the pattern and interconnected to a range of different types of circuits: linear connections, feedback loops, as well as branching and converging pathways. We conclude that in spite of the severe geometric restrictions, a complex repertoire of different connectivity patterns can form along the provided pathways. At the same time, network complexity is kept low enough to allow the study of these patterns at the resolution of single cell-cell contacts.

Effects of lead-contaminated sediment and nutrition on mallard duckling brain growth and biochemistry.

Day-old mallard (Anas platyryhnchos) ducklings received either a clean sediment (24%) supplemented control diet, Coeur d'Alene River Basin, Idaho (CDARB) sediment (3449 microg/g lead) supplemented diets at 12% or 24%, or a positive control diet (24% clean sediment with equivalent lead acetate to the 24% CDARB diet) for 6 weeks. The 12% CDARB diet resulted in a geometric mean concentration of 396 ppb (WW) brain lead with decreased brain protein and ATP concentrations but increased oxidized glutathione (GSSG) relative to the control diet. The 24% CDARB diet resulted in a concentration of 485 ppb brain lead with lower brain weight and ATP concentration than controls but higher concentrations of reduced glutathione (GSH) and calcium. Lead acetate accumulated twice as well as CDARB derived lead and resulted in histopathological lesions of the brain. With a combination of a suboptimal diet and 24% CDARB, brain lead concentration was higher (594 ppb) than with 24% CDARB in the standard diet, histopathological lesions became apparent and GSH was higher than suboptimal diet controls.

Copper deficiency as an anti-cancer strategy.

Copper is a tightly regulated trace element. Disruptions of copper homeostasis are rare and they cause serious disorders such as Wilson's disease and Menkes disease. Copper also plays an important role in promoting physiological and malignant angiogenesis. Formation of new blood vessels by a tumor enables tumor growth, invasion and metastasis. The copper chelator tetrathiomolybdate (TM), which quickly and effectively depletes copper stores, is under investigation as an anti-angiogenic agent. Promising results in vitro, in pre-clinical animal models and in an early (phase I) clinical trial have led to ongoing phase II evaluation of TM in patients with advanced cancers.

Patterning to enhance activity of cultured neuronal networks.

Embryonic rat hippocampal neurons were cultured in order to gain insights into how small networks of neurons interact. The principal observations are the electrical activities recorded with the electrode arrays, primarily action potentials both spontaneous and evoked. Several lithographic techniques were developed for controlling with micrometer precision the patterns of surface molecules in order to control neuronal attachment and growth. Cytophilic polylysine against protein repellent and hence cytophobic polyethylene glycol were used. By combining the cellular lithography with the microelectrode arrays it was possible to guide neurons preferentially to electrodes and to begin to investigate the question as to whether the geometric pattern of a neuronal network influences the patterns of its neuroelectric activity. It is clear that the techniques are adequate to ensure contact of neurons to electrodes but not to ensure the recording of signals, even when neurons lie directly on top of electrodes. The maturation of neuroelectric activity depends on the growth of glia within the culture, such that spontaneous activity appears to become robust when the number of glia is roughly the same as the number of neurons.

Higher respiratory rates and improved creatine stimulation in brain mitochondria isolated with anti-oxidants.

We tested the effect of an anti-oxidant mixture on respiration in isolated rat brain mitochondria. Mitochondria were isolated in mannitol/sucrose/EGTA/BSA +/- SCAVEGR anti-oxidants (SOD, catalase, vitamin E, vitamin E acetate, and glutathione reduced). TBARS were reduced by greater than 40% with SCAVEGR. Respiration driven by ADP showed a two-fold higher V(max) and a 15% higher respiratory control ratio when mitochondria were prepared with SCAVEGR. SCAVEGR also stabilized the octameric state of mitochondrial creatine kinase and thus improved creatine-stimulated respiration. These results suggest that significant improvements in brain mitochondrial function are obtained by isolation in the presence of an anti-oxidants mixture.

Tetrathiomolybdate anticopper therapy for Wilson's disease inhibits angiogenesis, fibrosis and inflammation.

The need for agents to lower body copper in Wilson's disease, a disease which results from copper toxicity has been the driving force for the development of the effective anticopper drugs penicillamine, trientine, zinc, and now tetrathiomolybdate (TM). Because of its rapid action, potency, and safety, TM is proving to be a very effective drug for initial treatment of acutely ill Wilson's disease patients. Beyond this, TM has antiangiogenic effects, because many proangiogenic cytokines require normal levels of copper. This has led to use of TM in cancer, where it is generally effective in animal tumor models, and has shown efficacy in preliminary clinical studies. Most recently, it has been found that TM has antifibrotic and antiinflammatory effects through inhibition of profibrotic and proinflammatory cytokines.