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The importance of Zn for human health becomes obvious during Zn deficiency. Even mild insufficiencies of Zn cause alterations in haematopoiesis and immune functions, resulting in a proinflammatory phenotype and a disturbed redox metabolism. Although immune system malfunction has the most obvious effect, the functions of several tissue cell types are disturbed if Zn supply is limiting. Adhesion molecules and tight junction proteins decrease, while cell death increases, generating barrier dysfunction and possibly organ failure. Taken together, Zn deficiency both weakens the resistance of the human body towards pathogens and at the same time increases the danger of an overactive immune response that may cause tissue damage. The case numbers of Corona Virus Disease 19 (COVID-19) are still increasing, which is causing enormous problems for health systems and economies. There is an urgent need to reduce both the number of severe cases and the resulting deaths. While therapeutic options are still under investigation, and first vaccines have been approved, cost-effective ways to reduce the likelihood of or even prevent infection, and the transition from mild symptoms to more serious detrimental disease, are highly desirable. Nutritional supplementation might be an effective option to achieve these aims. In this review, we discuss known Zn deficiency effects in the context of an infection with Severe Acute Respiratory Syndrome-Coronavirus-2 and its currently known pathogenic mechanisms and elaborate on how severe pre-existing Zn deficiency may pre-dispose patients to a severe progression of COVID-19. First published clinical data on the association of Zn homoeostasis with COVID-19 and registered studies in progress are listed.
Results of a co-morbid insomnia and depression study of eszopiclone and fluoxetine demonstrated that co-therapy produced greater improvements in sleep and depression than fluoxetine monotherapy. To determine if changes in the HAMD17 were due to sleep, individual HAMD17 items were evaluated.
Patients met DSM-IV criteria for MDD and insomnia, with screening HAMD17 >14. All patients received fluoxetine QAM for 10 weeks, and randomly received double-blind eszopiclone 3mg or placebo QHS for 8 weeks, followed by a single-blind placebo 2-week run-out. HAMD17 was completed at Weeks 4, 8, and 10. Individual items were compared with ANCOVA using an LOCF approach.
Mean baseline HAMD17 scores were 22 for each group. At Week 4, differences were noted between treatment groups in the total score, and the individual items of insight, the three insomnia items (p<0.02 vs monotherapy), with a trend for guilt (p=0.07). At Week 8, significant differences between groups were noted in total score (p=0.0005), in the clinician-administered Bech subscale (p<0.001), in the three insomnia items (p<0.001), guilt, work/activities, and anxiety psychic (p<0.05). At Week 10, the total score, guilt, the three insomnia items, work/activities, retardation, agitation, anxiety psychic, general somatic symptoms, and hypochondriasis demonstrated significant improvements (p<0.05 vs monotherapy) despite discontinuation of eszopiclone.
Eszopiclone/fluoxetine co-therapy resulted in significant improvements in the insomnia items of the HAMD17. In addition, several items related to core depressive symptoms were also improved with co-therapy compared with monotherapy.
We investigated the impact of eszopiclone 3mg on next day driving ability (on-the-road brake-reaction-time, BRT) and cognitive and psychomotor performance in patients with primary insomnia.
Patients with DSM-IV primary insomnia completed this study. Treatment was administered 30min before bedtime, and next day driving ability was assessed by on-the-road BRT approximately 9.5 hours postdose. A cognitive test battery measured residual effects on information processing, divided attention, psychomotor tasks, and working memory. Overnight polysomnography was conducted to assess sleep architecture; subjective ratings of morning sedation and sleep quality were also obtained.
There were no significant differences in BRT following night time administration of eszopiclone 3mg compared with placebo (p=0.39) and there were no significant differences in objective cognitive tests of information processing, divided attention, psychomotor tasks and working memory (p values>0.15). No significant effect on subjective next day ratings of morning sedation, coordination or mood was observed (p values>0.22). There was improvement compared with placebo (p<0.0001) in subjective ease of getting to sleep and quality of sleep the morning following dosing, and no perceived impairment of behavior following awakening or early morning awakenings. Polysomnography demonstrated significant improvements in sleep onset and maintenance.
In this study, the first to assess next day on-the-road driving in primary insomniacs following hypnotic use, eszopiclone 3mg improved both objective and subjective measures of sleep onset and maintenance without residual impairments on next day driving ability or cognitive and psychomotor performance.
Support for this study provided by Sepracor Inc., Marlborough, MA.
In the present study two broad hypotheses about the origins of self-mutilation in psychiatric patients were evaluated. The first hypothesis states that self-mutilation originates from child abuse and experiences of neglect and is connected to dissociation in later life. The second hypothesis views self-mutilation as the consequence of impulse control problems. To test these two hypotheses, data concerning traumatic childhood experiences and dissociative symptoms (hypothesis 1), as well as data concerning aggressiveness, obsessive-compulsiveness and sensation seeking (hypothesis 2) were collected in a sample of 54 psychiatric inpatients. Twenty-four out of 54 patients (44%) reported having engaged in self-mutilation. Mean age of onset of this behaviour was 23 years. Self-report measures of self-mutilators were more in line with the first than with the second hypothesis. That is, patients who engaged in self-mutilation reported more traumatic childhood experiences and dissociative symptoms than did control patients. The two groups did not differ in terms of aggressiveness, obsessive-compulsiveness, and sensation seeking. In line with earlier studies, the current results indicate that self-mutilating behaviour is linked to a history of abuse and neglect.
Rodent models of schizophrenia (SCZ) are indispensable when screening for novel treatments, but quantifying their translational relevance with the underlying human pathophysiology has proved difficult. A novel systems methodology (shown in Figure 1) was developed integrating and comparing proteomic data of anterior prefrontal cortex tissue from SCZ post-mortem brains and matched controls with data obtained from four established glutamatergic rodent models, with the aim of evaluating which of these models represent SCZ most closely. Liquid chromatography coupled tandem mass spectrometry (LC-MSE) proteomic profiling was applied comparing healthy and “disease state” in human post-mortem samples and rodent brain tissue samples. Protein-protein interaction networks were constructed from significant abundance changes and enrichment analyses enabled the identification of pathophysiological characteristics of the disorder, which were represented across all four rodent models. Subsequently, these functional domains were used for cross-species comparisons. Five functional domains such as “development and differentiation” represented across all four rodent models, were identified. It was quantified that the chronic phencyclidine (cPCP) model represented SCZ brain changes most closely for four of these functional domains, by using machine-learning techniques. This is the first study aiming to quantify which rodent model recapitulates the neuropathological features of SCZ most closely. The methodology and findings presented here support recent efforts to overcome translational hurdles of preclinical psychiatric research by associating behavioural endophenotypes with distinct biological processes.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Objectives: A wealth of studies provide evidence for action simulation during language comprehension. Recent research suggests such action simulations might be sensitive to fine-grained information, such as speed. Here, we present a crucial test for action simulation of speed in language by assessing speed comprehension in patients with Parkinson’s disease (PD). Based on the patients’ motor deficits, we hypothesized that the speed of motion described in language would modulate their performance in semantic tasks. Specifically, they would have more difficulty processing language about relatively fast speed than language about slow speed. Methods: We conducted a semantic similarity judgment task on fast and slow action verbs in patients with PD and age-matched healthy controls. Participants had to decide which of two verbs most closely matched a target word. Results: Compared to controls, PD patients were slower making judgments about fast action verbs, but not for judgments about slow action verbs, suggesting impairment in processing language about fast action. Moreover, this impairment was specific to verbs describing fast action performed with the hand. Conclusions: Problems moving quickly lead to difficulties comprehending language about moving quickly. This study provides evidence that speed is an important part of action representations. (JINS, 2017, 23, 412–420)
Reduction of the CP content in the diets of piglets requires supplementation with crystalline essential amino acids (AA). Data on the leucine (Leu) and histidine (His) requirements of young pigs fed low-CP diets are limited and have primarily been obtained from nonlinear models. However, these models do not consider the possible decline in appetite and growth that can occur when pigs are fed excessive amounts of AA such as Leu. Therefore, two dose-response studies were conducted to estimate the standardised ileal digestible (SID) Leu : lysine (Lys) and His : Lys required to optimise the growth performance of young pigs. In both studies, the average daily gain (ADG), average daily feed intake (ADFI) and gain-to-feed ratio (G : F) were determined during a 6-week period. To ensure that the diets had sub-limiting Lys levels, a preliminary Lys dose-response study was conducted. In the Leu study, 60 35-day-old piglets of both sexes were randomly assigned to one of five treatments and fed a low-CP diet (15%) with SID Leu : Lys levels of 83%, 94%, 104%, 115% or 125%. The His study used 120 31-day-old piglets of both sexes, which were allotted to one of five treatments and fed a low-CP diet (14%) with SID His : Lys levels of 22%, 26%, 30%, 34% or 38%. Linear broken-line, curvilinear-plateau and quadratic-function models were used for estimations of SID Leu : Lys and SID His : Lys. The minimum SID Leu : Lys level needed to maximise ADG, ADFI and G : F was, on average, 101% based on the linear broken-line and curvilinear-plateau models. Using the quadratic-function model, the minimum SID Leu : Lys level needed to maximise ADG, ADFI and G : F was 108%. Data obtained from the quadratic-function analysis further showed that a ±10% deviation from the identified Leu requirement was accompanied by a small decline in the ADG (−3%). The minimum SID His : Lys level needed to maximise ADG, ADFI and G : F was 27% and 28% using the linear broken-line and curvilinear-plateau models, respectively, and 33% using the quadratic-function model. The preferred model to estimate the His requirement was the curvilinear-plateau model. However, a 10% reduction in the SID His : Lys level was associated with an 11% reduction in the ADG. In conclusion, the SID Leu : Lys level needed to maximise growth was 108% when using the quadratic-function model as the best-fitting model. The minimum SID His : Lys level required to optimise growth was 28% when using the curvilinear-plateau model as the best-fitting model.
A lower molar of Castor fiber from the sandpit of Langenboom (the Netherlands) represents, so far, the oldest occurrence of a beaver in the North Sea Basin. Its presence in the marine sand deposit of the Langenboom Formation indicates that Castor fiber inhabited areas in or near the river systems of Rhine and Meuse in the Early Pliocene.
This study aimed to: (1) determine concordance rates of self-reported and subjectively determined indicators of oral malodor in twins; (2) determine the relative contributions of genetic and environmental factors to levels of volatile sulfur compounds (VSCs) in intraoral and exhaled breath. Fifty-one twin pairs participated in the study. Measurements of VSCs were obtained by a halimeter. The presence of tongue coatings was determined and twins filled out a 32-item questionnaire on oral malodor indicators independently of one another. Estimates of heritability (h2) for halimeter measurements were computed by SOLAR. The concordance rates for the presence of tongue coating among identical and fraternal twins were 67% and 11%, respectively. In the 10 most informative items, 70% exhibited higher concordance rates for identical than for fraternal twins. Of particular interest were the differences in concordance rates for dry mouth, sinus infection and unusual sweating. The h2 for intra-oral breath was 0.28 ± 0.17 (NS), whereas the h2 for exhaled breath was 0.50 ± 0.20 (p = .0207). The concordance rates of tongue coatings and malodor indicators were higher in identical twins than in fraternal twins. Intraoral breath VSC values were primarily attributable to environmental factors, whereas exhaled breath VSC values were partially explained by genetic factors.
Despite electrification, over 90% of rural households in certain areas of South Africa continue to depend on fuelwood, and this affects woody vegetation structure, with associated cascading effects on biodiversity within adjacent lands. To promote sustainable use, the interactions between anthropogenic and environmental factors affecting vegetation structure in savannahs need to be understood. Airborne light detection and ranging (LiDAR) data collected over 4758 ha were used to examine woody vegetation structure in five communal rangelands around 12 settlements in Bushbuckridge, a municipality in the Kruger to Canyons Biosphere Reserve (South Africa). The importance of underlying abiotic factors was evaluated by measuring size class distributions across catenas and using canonical correspondence analysis. Landscape position was significant in determining structure, indicating the importance of underlying biophysical factors. Differences in structure were settlement-specific, related to mean annual precipitation at one site, and human population density and intensity of use at the other four sites. Size class distributions of woody vegetation revealed human disturbance gradients around settlements. Intensity of use affected the amplitude, not the shape, of the size class distribution, suggesting the same height classes were being harvested across settlements, but amount harvested varied between settlements. Highly used rangelands result in a disappearance of disturbance gradients, leading to homogeneous patches of low woody cover around settlements with limited rehabilitation options. Reductions in disturbance gradients can serve as early warning indicators of woodland degradation, a useful tool in planning for conservation and sustainable development.
We report on the optical and charge transport properties of novel alkali metal chalcogenides, Cs2Hg6S7 and Cs2Cd3Te4, pertaining to their use in radiation detection. Optical absorption, photoconductivity, and gamma ray response measurements for undoped crystals were measured. The band gap energies of the Cs2Hg6S7 and Cs2Cd3Te4 compounds are 1.63 eV and 2.45 eV, respectively. The mobility-lifetime products for charge carriers are of the order of ~10-3 cm2/V for electrons and ~10-4 cm2/V for holes. Detectors fabricated from the ternary compound Cs2Hg6S7 shows well-resolved spectroscopic features at room temperature in response to ϒ -rays at 122 keV from a 57Co source, indicating its potential as a radiation detector.
We address the issue of decreasing band-gap with increasing atomic number, inherent in semiconducting materials, by introducing a concept we call dimensional reduction. The concept leads to semiconductor compounds containing high atomic number elements and simultaneously exhibiting a large band gap and high mass density suggesting that dimensional reduction can be successfully employed in developing new γ-ray detecting materials. As an example we discuss the compound Cs2Hg6S7 that exhibits a band-gap of 1.65eV and mobility-lifetime products comparable to those of optimized Cd0.9Zn0.1Te.
Scanning electron microscopy (SEM) can produce striking three-dimensional images of biological cells and tissues with submicron resolution of surface morphology. Such cell surfaces are often complex blends of folds, extrusions, and pockets that may be necessary in the positioning of specific molecules within interaction range of each other. Thus, surface changes can have a spatial control over some molecular functions, and identification of select molecules at distinct morphological locations becomes critical to our understanding of total cell function.
We simulate fusion in a Z-pinch, where the load is a xenon-plasma liner imploding onto a deuterium–tritium (DT) plasma target and the driver is a 2 MJ, 17 MA, 95 ns risetime pulser. The implosion system is modeled using the dynamic, 2D, radiation-magnetohydrodynamic code, MACH2. During implosion a shock forms in the Xe liner, transporting current and energy radially inward. After collision with the DT, a secondary shock forms pre-heating the DT to several hundred electronvolts. Adiabatic compression leads subsequently to a fusion burn, as the target is surrounded by a flux-compressed, intense, azimuthal-magnetic field. The intense-magnetic field confines fusion α-particles, providing an additional source of ion heating that leads to target ignition. The target remains stable up to the time of ignition. Predictions are for a neutron yield of 3.0 × 1019 and a thermonuclear energy of 84 MJ, that is, 42 times greater than the initial, capacitor-stored energy.
Oral microbes that colonize in the mouths of humans contribute to disease susceptibility, but it is unclear if host genetic factors mediate colonization. We therefore tested the hypothesis that the levels at which oral microbes colonize in the mouth are heritable. Dental plaque biofilms were sampled from intact tooth surfaces of 118 caries-free twins. An additional 86 caries-active twins were sampled for plaque from carious lesions and intact tooth surfaces. Using a reverse capture checkerboard assay the relative abundance of 82 bacterial species was determined. An integrative computational predictive model determined microbial abundance patterns of microbial species in caries-free twins as compared to caries-active twins. Heritability estimates were calculated for the relative microbial abundance levels of the microbial species in both groups. The levels of 10 species were significantly different in healthy individuals than in caries-active individuals, including, A. defectiva, S. parasanguinis, S. mitis/oralis, S. sanguinis, S. cristatus, S. salivarius, Streptococcus sp. clone CH016, G. morbillorum and G. haemolysans. Moderate to high heritability estimates were found for these species (h2 = 56%–80%, p < .0001). Similarity of the overall oral microbial flora was also evident in caries-free twins from multivariate distance matrix regression analysis. It appears that genetic and/or familial factors significantly contribute to the colonization of oral beneficial species in twins.
It is unclear whether medical or invasive (surgical or catheter interventional) treatment is preferable to prevent recurrence of cerebral ischemia in patients with patent foramen ovale (PFO) as the suspected cause of stroke and what the role of concomitant risk factors is in stroke recurrence.
Over a period of ten years, 124 patients (mean age 51 ± 15 years) with cryptogenic cerebral ischemia and PFO were included into the study and prospectively followed over a mean of 52 ± 32 months. Of these, 83 were treated medically, 34 underwent transcatheter closure, and seven had surgical closure of the foramen. Of the medically treated patients, 11 stopped medication during follow-up. Recurrent ischemic events and risk factors for recurrence were analyzed.
Annual stroke recurrence rates were generally low and comparable in catheter and medically treated patients, and in patients who had stopped medication (2.9%/2.1%/2.2%/year). Patients suffering from recurrence after transcatheter closure (n=2) both had residual shunts. No stroke recurrence was observed in the few surgically treated patients. An atrial septal aneurysm was not a predictor of recurrent or multiple strokes (p>0.05, OR=0.31, and OR=0.74). Large shunts and a history of previous ischemic events were considerably more frequent in patients with recurrent strokes (p<0.05, OR=5.0, and OR=4.4). Pulmonary embolism and case fatality rates were significantly higher in patients with stroke recurrence (p<0.001, and p<0.01).
The absolute risk of recurrent cerebrovascular events in patients with PFO receiving medical or catheter interventional therapy is low. The small group of untreated patients had a comparably low rate of stroke recurrences. Previous ischemic events and shunt size were risk factors in this observational study. Given conflicting findings across multiple studies, enrollment into a randomized controlled trial would be the optimal choice.