Experimental and epidemiological studies implicate the cannabinoid 1 receptor (CB1R) in the pathophysiology of psychosis. However, whether CB1R levels are altered in the early stages of psychosis and ...whether they are linked to cognitive function or symptom severity remain unknown.
To investigate CB1R availability in first-episode psychosis (FEP) without the confounds of illness chronicity or the use of illicit substances or antipsychotics.
This cross-sectional, case-control study of 2 independent samples included participants receiving psychiatric early intervention services at 2 independent centers in Turku, Finland (study 1) and London, United Kingdom (study 2). Study 1 consisted of 18 volunteers, including 7 patients with affective or nonaffective psychoses taking antipsychotic medication and 11 matched controls; study 2, 40 volunteers, including 20 antipsychotic-naive or antipsychotic-free patients with schizophrenia or schizoaffective disorder and 20 matched controls. Data were collected from January 5, 2015, through September 26, 2018, and analyzed from June 20, 2016, through February 12, 2019.
The availability of CB1R was indexed using the distribution volume (VT, in milliliters per cubic centimeter) of 2 CB1R-selective positron emission tomography radiotracers: fluoride 18-labeled FMPEP-d2 (study 1) and carbon 11-labeled MePPEP (study 2). Cognitive function was measured using the Wechsler Digit Symbol Coding Test. Symptom severity was measured using the Brief Psychiatric Rating Scale for study 1 and the Positive and Negative Syndrome Scale for study 2.
A total of 58 male individuals were included in the analyses (mean SD age of controls, 27.16 5.93 years; mean SD age of patients, 26.96 4.55 years). In study 1, 7 male patients with FEP (mean SD age, 26.80 5.40 years) were compared with 11 matched controls (mean SD age, 27.18 5.86 years); in study 2, 20 male patients with FEP (mean SD age, 27.00 5.06 years) were compared with 20 matched controls (mean SD age, 27.15 6.12 years). In study 1, a significant main effect of group on 18FFMPEP-d2 VT was found in the anterior cingulate cortex (ACC) (t16 = -4.48; P < .001; Hedges g = 1.2), hippocampus (t16 = -2.98; P = .006; Hedges g = 1.4), striatum (t16 = -4.08; P = .001; Hedges g = 1.9), and thalamus (t16 = -4.67; P < .001; Hedges g = 1.4). In study 2, a significant main effect of group on 11CMePPEP VT was found in the ACC (Hedges g = 0.8), hippocampus (Hedges g = 0.5), striatum (Hedges g = 0.4), and thalamus (Hedges g = 0.7). In patients, 11CMePPEP VT in the ACC was positively associated with cognitive functioning (R = 0.60; P = .01), and 11CMePPEP VT in the hippocampus was inversely associated with Positive and Negative Syndrome Scale total symptom severity (R = -0.50; P = .02).
The availability of CB1R was lower in antipsychotic-treated and untreated cohorts relative to matched controls. Exploratory analyses indicated that greater reductions in CB1R levels were associated with greater symptom severity and poorer cognitive functioning in male patients. These findings suggest that CB1R may be a potential target for the treatment of psychotic disorders.
Cystic Fibrosis (CF) is an autosomal recessive genetic disease. Two models for screening CF are normally used: newborn screening and population-based CF carrier screening. In turn, there are three ...main models of population-based CF carrier screening: prenatal carrier screening, preconception carrier screening, and carrier screening outside clinical settings.
To evaluate, in the light of the personalist view, the use of carrier screenings for CF outside the clinic, i.e. in non-clinical settings, such as school and workplaces.
Analysis has been carried out according to the "Personalist approach" (also called "Triangular model"), an ethical method for performing ethical analysis within HTA process. It includes factual, anthropological and ethical data in a ''triangular'' normative reflection process.
Implementing carrier screening for cystic fibrosis outside the clinical settings allows acquisition of knowledge for informing reproductive choices, that can be considered as valuable; benefit-risk ratio seems to be not much favorable; autonomous and responsible decisions can be taken only under certain conditions; economic advantage is difficult to determine; therefore, from a personalist view, implementing carrier screenings outside the clinic seems not to be ethically justified.
In accordance with the personalist perspective, public health programs providing carrier screenings outside the clinic should not be implemented.
Genetic tests affect not only single patients but also their genetic relatives. In some cases, they in fact allow to acquire information not only about a single patient, but also about those who are ...genetically linked (genetic relatives). By appealing to the principle of autonomy, the patient can refuse to be informed of the test result, or to inform their relatives on the risk of a pathology. How might the relatives' right to know be reconciled with the will of a patient who refuses to know or to inform? Among the large number of moral dilemmas that this field can raise, the article aims to reply to the above mentioned question and to analyse in depth some aspects of intra-family communication within the field of genetic tests for cancer.
The Popeye domain-containing 1 (POPDC1) gene encodes a plasma membrane-localized cAMP-binding protein that is abundantly expressed in striated muscle. In animal models, POPDC1 is an essential ...regulator of structure and function of cardiac and skeletal muscle; however, POPDC1 mutations have not been associated with human cardiac and muscular diseases. Here, we have described a homozygous missense variant (c.602C>T, p.S201F) in POPDC1, identified by whole-exome sequencing, in a family of 4 with cardiac arrhythmia and limb-girdle muscular dystrophy (LGMD). This allele was absent in known databases and segregated with the pathological phenotype in this family. We did not find the allele in a further screen of 104 patients with a similar phenotype, suggesting this mutation to be family specific. Compared with WT protein, POPDC1(S201F) displayed a 50% reduction in cAMP affinity, and in skeletal muscle from patients, both POPDC1(S201F) and WT POPDC2 displayed impaired membrane trafficking. Forced expression of POPDC1(S201F) in a murine cardiac muscle cell line (HL-1) increased hyperpolarization and upstroke velocity of the action potential. In zebrafish, expression of the homologous mutation (popdc1(S191F)) caused heart and skeletal muscle phenotypes that resembled those observed in patients. Our study therefore identifies POPDC1 as a disease gene causing a very rare autosomal recessive cardiac arrhythmia and LGMD, expanding the genetic causes of this heterogeneous group of inherited rare diseases.
Abstract
Background
Genomic testing expansion for hereditary breast and ovarian cancer (HBOC) comes with an increased need for genetic counseling and intra-familial communication. Genetic counseling ...can play an important role in facilitating intra-familial communication and relationships, thus avoiding misunderstandings within the family.
Methods
We conducted a cross-sectional, multicenter study including 252 Italian women, using a questionnaire divided in two sections; the first to be filled after the pre-test counseling and the second after receiving the genetic test results. This aimed at assessing the factors influencing the disclosure of genetic information for HBOC, family members that probands share genetic information with, and the degree of understanding of the information received by the counselees during genetic counseling.
Results
Women were accompanied to the counseling more by their husbands/partners. Among those with a positive test result, 49% shared it with their offspring and 27 % with their husband/partner. Younger women, those living with their husbands/partners and those who described family communication as open/deep had a higher probability of being accompanied at the genetic counseling and discuss about it with relatives. Being alone at the genetic counseling was significantly associated to non-existing familial relationship (p = 0.003) and problematic intra-familial communication (p = 0.005). Sincere or joyful familial relations were associated with the decision to undergo genetic testing as a responsibility towards relatives. Women had a good understanding of the counseling (mean score 9.2 in a scale1-10).
Discussion
Genetic counseling providers should consider that the disclosure of genetic information does not depend only on the clarity of the information provided, but also on pre-existing intra-familial communication and relationship, family structure and marital status, indicating the need of a personalized approach based on these factors.
Key messages
The disclosure of genetic information from women to their relatives in the case of HBOC is a complex relational process, which poses practical and ethical problems for individuals and families. Genetic counseling providers should be able to advice their patients on the importance of genetic information disclosure, considering, also, the pre-existing intra-familial communication dynamics.
Geophysical sensors combined with machine learning
algorithms were used to understand the pedosphere system and landscape
processes and to model soil attributes. In this research, we used parent
...material, terrain attributes, and data from geophysical sensors in different
combinations to test and compare different and novel machine learning
algorithms to model soil attributes. We also analyzed the importance of
pedoenvironmental variables in predictive models. For that, we collected
soil physicochemical and geophysical data (gamma-ray emission from uranium,
thorium, and potassium; magnetic susceptibility and apparent electric
conductivity) by three sensors (gamma-ray spectrometer, RS 230;
susceptibilimeter KT10, Terraplus; and conductivimeter, EM38 Geonics) at
75 points and analyzed the data. The models with the best performance
(R2 0.48, 0.36, 0.44, 0.36, 0.25, and 0.31) varied for clay, sand,
Fe2O3, TiO2, SiO2, and cation exchange capacity
prediction, respectively. Modeling with the selection of covariates at three
phases (variance close to zero, removal by correction, and removal by
importance) was adequate to increase the parsimony. The results were
validated using the method “nested leave-one-out cross-validation”. The
prediction of soil attributes by machine learning algorithms yielded
adequate values for field-collected data, without any sample preparation,
for most of the tested predictors (R2 values ranging from 0.20 to
0.50). Also, the use of four regression algorithms proved to be important
since at least one of the predictors used one of the tested algorithms. The
performance values of the best algorithms for each predictor were higher
than those obtained with the use of a mean value for the entire area
comparing the values of root mean square error (RMSE) and mean absolute
error (MAE). The best combination of sensors that reached the highest model
performance was that of the gamma-ray spectrometer and the
susceptibilimeter. The most important variables for most
predictions were parent material,
digital elevation, standardized height, and magnetic susceptibility. We concluded that soil attributes can be efficiently modeled
by geophysical data using machine learning techniques and geophysical sensor
combinations. This approach can facilitate future soil mapping in a more
time-efficient and environmentally friendly manner.
•Lithology, pedogenesis and relief affect soil magnetic susceptibility.•Pedogenesis strongly affect magnetic susceptibility on more evolved soil classes.•Lithology contribute more to magnetic ...susceptibility in less evolved soil classes.•Magnetic susceptibility had good correlation with soil texture, CEC and iron content.•Field sensor can be used in delimitation of soil classes and digital soil mapping.
Soil magnetic susceptibility (κ) has potential to be used as a pedoenvironmental indicator from which mineralogy, pedogeochemical, pedogeomorphological and pedogenic processes can be inferred. It can be used in pedosphere studies, as an auxiliary information for appropriate and sustainable soil use and management. This research aimed to analyze how pedogenesis and geochemical processes affect the κ and some of its attributes, as well as its potential use in discriminating soil great groups, following the digital soil mapping approach. The study area is located in São Paulo State - Brazil. Soil samples were collected for physical–chemical analysis from 79 locations (0–20 cm depth). At these sites, magnetic susceptibility was measured with a portable field instrument and analyzed in terms of geology, relief and soil class. The results showed that geology strongly affects κ, mainly in diabase derived soils, followed by metamorphosed siltstone and siltstone. In fluvial sediments, the κ exhibits different behaviors due to different sediments deposited by the Capivari River. In less evolved soils, such as Cambisols, lithology is a more important contributor to κ than pedogenesis. In more evolved soils, pedogenesis increases κ, whereas argilluviation/ferralitization reduces it. The κ values did not decrease significantly or even increase downslope, due to the presence of diabase on the lower parts. Differences in κ where observed between diabase bedrock located in different parts of the study area, indicating more of an influence by geomorphic processes rather than lithology. With respect to soil attributes, positive correlations between κ and base saturation, cation exchange capacity, organic matter, and iron and clay content were found, whereas a negative correlation was found between κ and sand content. The κ correlates with changes in lithology and soil class demonstrating its application as a potential tool for the discrimination of soil great groups and digital soil mapping.
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