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Spatial disorientation is common in Alzheimer’s disease (AD), Mild Cognitive Impairment (MCI), and preclinical individuals with AD biomarkers. However, traditional neuropsychological tests lack ecological validity for the assessment of spatial orientation and to date, there is still no gold standard. The current study aimed to determine the validity and accuracy of two virtual reality tasks for the assessment of spatial orientation.
We adapted two spatial orientation tasks to immersive virtual environments: a “survey to route” task in which participants had to transfer information from a map to their body position within a maze [Spatial Orientation in Immersive Virtual Environment Test (SOIVET) Maze], and an allocentric-type, route learning task, with well-established topographic landmarks (SOIVET Route). A total of 19 MCI patients and 29 cognitively healthy older adults aged 61–92 participated in this study. Regular neuropsychological assessments were used for correlation analysis and participant performances were compared between groups. Receiver Operating Characteristic (ROC) curve analysis was performed for accuracy.
The SOIVET Maze correlated with measures of visuoperception, mental rotation, and planning, and was not related to age, educational level, or technology use profile. The SOIVET Route immediate correlated with measures of mental rotation, memory, and visuoconstruction, and was influenced only by education. Both tasks significantly differentiated MCI and control groups, and demonstrated moderate accuracy for the MCI diagnosis.
Traditional neuropsychological assessment presents limitations and immersive environments allow for the reproduction of complex cognitive processes. The two immersive virtual reality tasks are valid tools for the assessment of spatial orientation and should be considered for cognitive assessments of older adults.
A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls.
This cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate.
ES-SCZ was associated with the GAF dimensions in patients (symptom: B = −1.53, p-value = 0.001; disability: B = −1.44, p-value = 0.001), siblings (symptom: B = −3.07, p-value < 0.001; disability: B = −2.52, p-value < 0.001), and healthy controls (symptom: B = −1.50, p-value < 0.001; disability: B = −1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group.
Our findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management.
Sex selection through sperm sorting offers advantages in regards selection pressure in high-producing livestock. However, the sex-sorting process results in sperm membrane and DNA damage that ultimately decrease fertility. We hypothesized that given the role of protamines in DNA packaging, protamine deficiency could account, at least partially, for the DNA damage observed following sperm sex sorting. To test this, we compared protamine status between unsexed and sexed spermatozoa from two bulls using the fluorochrome chromomycin A3 (CMA3) and flow cytometry. Then, we assessed embryo development following in vitro fertilization (IVF) using the same sperm treatments. Overall, sperm protamination was not different between sexed and unsexed semen. However, one of the two bulls displayed higher rates of protamine deficiency for both unsexed and sexed semen (P < 0.05). Moreover, unsexed semen from this bull yielded lower blastocyst (P < 0.05) and blastocyst hatching rates than unsexed sperm from the other bull. CMA3-positive staining was negatively correlated with cleavage (R2 85.1, P = 0.003) and blastocyst hatching (R2 87.6, P = 0.006) rates in unsexed semen. In conclusion, while the sex-sorting process had no effect on sperm protamine content, we observed a bull effect for sperm protamination, which correlated to embryo development rates following IVF.
The efficacy is measured for a public health intervention related to community-based planning for population protection measures (PPMs; ie, shelter-in-place and evacuation).
This is a mixed (qualitative and quantitative) prospective study of intervention efficacy, measured in terms of usability related to effectiveness, efficiency, satisfaction, and degree of community engagement.
Two municipalities in the Commonwealth of Puerto Rico are included.
Community members consisting of individuals; traditional leaders; federal, territorial, and municipal emergency managers; municipal mayors; National Guard; territorial departments of education, health, housing, public works, and transportation; health care; police; Emergency Medical Services; faith-based organizations; nongovernmental organizations (NGOs); and the private sector.
The intervention included four community convenings: one for risk communication; two for plan-writing; and one tabletop exercise (TTX). This study analyzed data collected from the project work plan; participant rosters; participant surveys; workshop outputs; and focus group interviews.
Main Outcome Measures:
Efficacy was measured in terms of ISO 9241-11, an international standard for usability that includes effectiveness, efficiency, user satisfaction, and “freedom from risk” among users. Degree of engagement was considered an indicator of “freedom from risk,” measurable through workshop attendance.
Two separate communities drafted and exercised ~60-page-long population protection plans, each within 14.5 hours. Plan-writing workshops completed 100% of plan objectives and activities. Efficiency rates were nearly the same in both communities. Interviews and surveys indicated high degrees of community satisfaction. Engagement was consistent among community members and variable among governmental officials.
Frontline communities have successfully demonstrated the ability to understand the environmental health hazards in their own community; rapidly write consensus-based plans for PPMs; participate in an objective-based TTX; and perform these activities in a bi-lingual setting. This intervention appears to be efficacious for public use in the rapid development of community-based PPMs.
There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation.
We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls.
The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: −0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465).
The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.
This study attempted to replicate whether a bias in probabilistic reasoning, or ‘jumping to conclusions’(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation.
Data were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses.
JTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46–5.17 for siblings and aRR: 5.07 CI 95% 4.13–6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67–8.51, and in patients: 2.15 CI 95% 0.94–4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences.
These findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations.
To examine the associations between vitamins of the methionine-homocysteine (Hcys) cycle (B6, B12 and folate) and Hcys with metabolic syndrome (MetS) among Mesoamerican children and their adult parents.
We conducted a cross-sectional study. Exposures were plasma vitamins B6 and B12 concentrations, erythrocyte folate and plasma Hcys. In children, the outcome was a continuous metabolic risk score calculated through sex- and age standardisation of waist circumference, the homoeostatic model assessment for insulin resistance, mean arterial pressure (MAP), serum HDL-cholesterol and serum TAG. In parents, the outcome was the prevalence of MetS according to the Adult Treatment Panel III Criteria. We estimated mean differences in the metabolic risk score and prevalence ratios of MetS between quartiles of the exposures using multivariable-adjusted linear and Poisson regression models, respectively.
Capital cities of Belize, Guatemala, El Salvador, the Dominican Republic, Honduras, Nicaragua, Panama, Costa Rica and Chiapas State in Mexico.
In total, 237 school-aged children and 524 parents.
Among children, vitamin B12 was inversely associated with the metabolic risk score (quartiles 4–1 adjusted difference = –0·13; 95 % CI: –0·21, –0·04; Ptrend = 0·008) through MAP, HDL-cholesterol and TAG. In contrast, folate was positively associated with the metabolic risk score (quartiles 4–1 adjusted difference = 0·11; 95 % CI: 0·01, 0·20; Ptrend = 0·02). In adults, vitamin B6 was inversely associated with MetS prevalence, whereas vitamin B12 and folate were positively related to this outcome.
Vitamins of the methionine-Hcys cycle are associated with MetS in different directions. The associations differ between children and adults.
Although the literature recognizes the participation of patients in medical decisions as an important indicator of quality, there is a lack of consensus regarding the influence of advance directives (ADs) on reducing aggressive measures during end-of-life care involving cancer patients.
A systematic review was conducted to analyze the influence of ADs on reducing aggressive end-of-life care measures for cancer patients.
We searched the Medline, Embase, Web of Science, and Lilacs databases for studies published until March 2018 using the following keywords, without language restrictions: “advance directives,” “living wills,” “terminal care,” “palliative care,” “hospice care,” and “neoplasms.” Article quality was assessed using study quality assessment tools from the Department of Health and Human Services (NHLBI).
A total of 1,489 studies were identified; 7 met the inclusion criteria. The studies were recently published (after 2014, 71.4%). Patients with ADs were more likely to die at the site of choice (n = 3) and received less chemotherapy in the last 30 days (n = 1). ADs had no impact on intensive care unit admission (n = 1) or hospitalization (n = 1). One study found an association between ADs and referral to palliative care, but other did not find the same result.
Significance of results
Of the seven articles found, four demonstrated effects of ADs on the reduction in aggressive measures at the end of life of cancer patients. Heterogeneity regarding study design and results and poor methodological quality are challenges when drawing conclusions.
We present two complementary model-based methods for calculating the risk of international spread of the novel coronavirus SARS-CoV-2 from the outbreak epicentre. One model aims to calculate the number of cases that would be exported from an endemic country to disease-free regions by travellers. The second model calculates the probability that an infected traveller will generate at least one secondary autochthonous case in the visited country. Although this paper focuses on the data from China, our methods can be adapted to calculate the risk of importation and subsequent outbreaks. We found an average R0 = 5.31 (ranging from 4.08 to 7.91) and a risk of spreading of 0.75 latent individuals per 1000 travellers. In addition, one infective traveller would be able to generate at least one secondary autochthonous case in the visited country with a probability of 23%.
The co-infection between visceral leishmaniasis (VL) and human immunodeficiency virus (HIV) has increased in several countries in the world. The current serological tests are not suitable since they present low sensitivity to detect the most of VL/HIV cases, and a more precise diagnosis should be performed. In this context, in the present study, an immunoproteomics approach was performed using Leishmania infantum antigenic extracts and VL, HIV and VL/HIV patients sera, besides healthy subjects samples; aiming to identify antigenic markers for these clinical conditions. Results showed that 43 spots were recognized by antibodies in VL and VL/HIV sera, and 26 proteins were identified by mass spectrometry. Between them, β-tubulin was expressed, purified and tested in ELISA experiments as a proof of concept for validation of our immunoproteomics findings and results showed high sensitivity and specificity values to detect VL and VL/HIV patients. In conclusion, the identified proteins in the present work could be considered as candidates for future studies aiming to improvement of the diagnosis of VL and VL/HIV co-infection.
Several studies have independently suggested that patients with schizophrenia are more likely to have an enlarged cavum septum pellucidum (CSP) and an absent adhesio interthalamica (AI), respectively. However, neither finding has been consistently replicated and it is unclear whether there is an association between these two midline brain abnormalities. Thus, we compared the prevalence of absent AI and the prevalence, size and volume of CSP in 38 patients with schizophrenia and 38 healthy controls using magnetic resonance imaging (MRI). There were no between group differences in the presence or volume of CSP; however, an enlarged CSP was commoner among patients than controls. There was also a positive correlation between CSP ratings and volumes. No differences in the presence or absence of the AI were found between patients and controls; however, an absent AI was commoner in male patients with schizophrenia than females. There was absolutely no overlap between the presence of a large CSP and an absence of AI. In conclusion, our findings are in line with several case series and other MRI investigations that have shown a higher incidence of putatively developmental brain abnormalities in patients with schizophrenia, particularly in males, and support the neurodevelopmental model of this disorder.
Less invasive protocols are necessary to study energy expenditure (EE) of cats living in homes for expressing their normal living conditions. The present study compared sampling times and the use of saliva, urine and blood to measure 2H and 18O to apply the doubly labelled water method. In the first study, four cats were used to evaluate the enrichment (2, 4, 6, 7 and 8 h) and elimination (2, 4, 6, 8, 10, 12, 14, 16, 18 and 20 d) of 2H and 18O (subcutaneously injected). The maximum enrichment was after 5 h (R2 0·82) of injection, with an Ln linear elimination of both isotopes (P < 0·001; R2 0·99). The results of EE were similar, regardless of the sampling time used (P = 0·999). In the second study, seven male cats and seven female cats were used. Before and after isotope injection (5 h, 7 d, 10 d and 14 d), blood, saliva and urine were collected. Isotope enrichment was lower in urine (P < 0·05) and at the similar level in blood and saliva. Isotope elimination was similar for all fluids (P < 0·473). The EE calculated with blood and saliva was similar but higher for urine (P = 0·015). According to Bland–Altman statistics, blood and saliva presented low bias and high correlation (P < 0·001), but this was not observed for urine (P = 0·096). Higher EE was observed for male cats (384 (se 39) kJ/kg0·67 per d) than for female cats (337 (se 34) kJ/kg0·67 per d; P < 0·05). The sampling time for the method is flexible, and saliva can be used as a substitute for blood.
Multi-Robot System (MRS) is composed of a group of robots that work cooperatively. However, Multi-Agent System (MAS) is computational systems consisting of a group of agents that interact with each other to solve a problem. The central difference between MRS and MAS is that in the first case, the agent is a robot, and in the second, it is a software. Analyzing the scientific literature, it is possible to notice that few studies address the integration between MAS and MRS. In order to achieve the interdisciplinary integration, the theoretical background of these areas must be considered in this paper, so that the integration can be applied using a case study of decentralized MRS. The objective of this MRS is to track and surround a stationary target. Also, it has been implemented and validated in the robot simulator called Virtual Robot Experimentation Platform (V-REP). In the validation of the proposed MRS, a scenario with three robots and a stationary target were defined. In the tracking task, the robot can detect the target whose position is not known a priori. When the detection occurs, the V-REP informs the target position to the robot because the environment is discretized into a grid of rectangular cells. After that, all the robots are directed to the target, and the surround task is realized. In this task, a mathematical model with direct communication between the robots was used to keep the robots equidistant therefrom and from each other.
First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.
We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.
In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.
The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
The VISCACHA (VIsible Soar photometry of star Clusters in tApii and Coxi HuguA†) Survey is an ongoing project based on deep and spatially resolved photometric observations of Magellanic Cloud star clusters, collected using the SOuthern Astrophysical Research (SOAR) telescope together with the SOAR Adaptive Module Imager. So far we have used >300h of telescope time to observe ∼150 star clusters, mostly with low mass (M < 104M⊙) on the outskirts of the LMC and SMC. With this high-quality data set, we homogeneously determine physical properties using deep colour-magnitude diagrams (ages, metallicities, reddening, distances, mass, luminosity and mass functions) and structural parameters (radial density profiles, sizes) for these clusters which are used as a proxy to investigate the interplay between the Magellanic Clouds and their evolution. We present the VISCACHA survey and its initial results, based on our first two papers. The project’s long term goals and expected legacy to the community are also addressed.
In the current study, phage-exposed mimotopes as targets against tegumentary leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of TL patients and healthy subjects, besides the immune stimulation of peripheral blood mononuclear cells (PBMCs) collected from untreated and treated TL patients and healthy subjects. The clones were evaluated regarding their specific interferon-γ (IFN-γ) and interleukin-4 (IL-4) production in the in vitro cultures, and selectivity and specificity values were calculated, and those presenting the best results were selected for the in vivo experiments. Two clones, namely A4 and A8, were identified and used in immunization protocols from BALB/c mice to protect against Leishmania amazonensis infection. Results showed a polarized Th1 response generated after vaccination, being based on significantly higher levels of IFN-γ, IL-2, IL-12, tumour necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF); which were associated with lower production of specific IL-4, IL-10 and immunoglobulin G1 (IgG1) antibodies. Vaccinated mice presented significant reductions in the parasite load in the infected tissue and distinct organs, when compared with controls. In conclusion, we presented a strategy to identify new mimotopes able to induce Th1 response in PBMCs from TL patients and healthy subjects, and that were successfully used to protect against L. amazonensis infection.
The 2008-2011 food price spikes brought the issue of postharvest losses (PHL) back to the forefront of policy debate, and observers are again calling for a reduction in PHL as a tool to feed the expanding global population. Food losses due to improper postharvest handling, lack of appropriate infrastructure, and poor management techniques, have once again become a matter of serious concern. Food losses, defined as “any decrease in food mass throughout the edible food supply chain,” can occur in any point of the marketing stages–from production (e.g., crop damage, spillage), postharvest and processing stages (e.g., attacks from insect or microorganisms during storage), distribution, and retail sale until home consumption (e.g., spoilage, table waste) (Rosegrant et al. 2013). Kummu et al. (2012) suggest an additional 1 billion people could be fed if food crop losses were halved, which could potentially relieve some of the pressure on the significant increase in production that would be required. Achieving lower levels of food losses, however requires both investments in technologies that help prevent losses as well as in overall infrastructure. Understanding the magnitude of these investments and their impact is key to establish that a reduction in PHL has in fact an impact on food security.
The anti-leishmania effects of HIV peptidase inhibitors (PIs) have been widely reported; however, the biochemical target and mode of action are still a matter of controversy in Leishmania parasites. Considering the possibility that HIV-PIs induce lipid accumulation in Leishmania amazonensis, we analysed the effects of lopinavir on the lipid metabolism of L. amazonensis promastigotes. To this end, parasites were treated with lopinavir at different concentrations and analysed by fluorescence microscopy and spectrofluorimetry, using a fluorescent lipophilic marker. Then, the cellular ultrastructure of treated and control parasites was analysed by transmission electron microscopy (TEM), and the lipid composition was investigated by thin-layer chromatography (TLC). Finally, the sterol content was assayed by gas chromatography–mass spectrometry (GC/MS). TEM analysis revealed an increased number of lipid inclusions in lopinavir-treated cells, which was accompanied by an increase in the lipophilic content, in a dose-dependent manner. TLC and GC–MS analysis revealed a marked increase of cholesterol-esters and cholesterol. In conclusion, lopinavir-induced lipid accumulation and affected lipid composition in L. amazonensis in a concentration–response manner. These data contribute to a better understanding of the possible mechanisms of action of this HIV-PI in L. amazonensis promastigotes. The concerted action of lopinavir on this and other cellular processes, such as the direct inhibition of an aspartyl peptidase, may be responsible for the arrested development of the parasite.
Selenium (Se) is an essential micronutrient for humans, yet its dietary intake is low, mostly due to the low bioavailability in soils and therefore in edible plant tissues. To overcome Se deficiency, the breeding approach (i.e., genetic biofortification), namely in rice, is largely dependent on available Se pools. To ensure the success of genetic biofortification with Se, agronomic biofortification can be accomplished through foliar Se application. Considering this background, the main hypothesis of this work was centered in the foliar application of Se to attain agronomic biofortification of rice crops. This study also aimed to assess the full potential for increasing grain Se concentrations during rice filling, as well as the types of nutrients deposition. An experimental design applying two foliar fertilizers (sodium selenite and sodium selenate) was developed. As test systems, four rice genotypes (Ariete, Albatros, OP1105 and OP1109) were used and the kinetics of micro- and macro-nutrients accumulation and deposition were assessed. Biofortification was performed in field trials for two years with foliar fertilization ranging between 0 and 300 g Se ha−1. At the end of the plant cycle, selenite applications triggered 427- to 884-fold increases in grain Se concentrations among rice genotypes (Albatros > OP1105 > OP1109 > Ariete). The application of selenate also prompted 128- to 347-fold increases in grain Se concentrations in rice crops (Albatros > OP1105 > Ariete > OP1109). Regardless of the foliar fertilizer applied, Se deposition among genotypes occurred throughout the grain without relevant inhibitory effects on yields. In each genotype, micro and macronutrients varied among crop tissues.