Polymorphisms in the circadian expressed genes PER3 and ARNTL2 are associated with diurnal preference and GNβ3 with sleep measures

Sleep and circadian rhythms are intrinsically linked, with several sleep traits, including sleep timing and duration, influenced by both sleep homeostasis and the circadian phase. Genetic variation in several circadian genes has been associated with diurnal preference (preference in timing of sleep), although there has been limited research on whether they are associated with other sleep measurements. We investigated whether these genetic variations were associated with diurnal preference (Morningness-Eveningness Questionnaire) and various sleep measures, including: the global Pittsburgh Sleep Quality index score; sleep duration; and sleep latency and sleep quality. We genotyped 10 polymorphisms in genes with circadian expression in participants from the G1219 sample (n = 966), a British longitudinal population sample of young adults. We conducted linear regressions using dominant, additive and recessive models of inheritance to test for associations between these polymorphisms and the sleep measures. We found a significant association between diurnal preference and a polymorphism in period homologue 3 (PER3) (P < 0.005, recessive model) and a novel nominally significant association between diurnal preference and a polymorphism in aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) (P < 0.05, additive model). We found that a polymorphism in guanine nucleotide binding protein beta 3 (GNβ3) was associated significantly with global sleep quality (P < 0.005, recessive model), and that a rare polymorphism in period homologue 2 (PER2) was associated significantly with both sleep duration and quality (P < 0.0005, recessive model). These findings suggest that genes with circadian expression may play a role in regulating both the circadian clock and sleep homeostasis, and highlight the importance of further studies aimed at dissecting the specific roles that circadian genes play in these two interrelated but unique behaviours

Una evaluación de la escala sobre el miedo a la COVID-19 en docentes filipinos profesionales.

The global Coronavirus Disease 2019 (COVID-19) crisis has enormously induced psychological impacts on humans like fear. Considering this particular concern, there is a need to test instruments used to measure such psychological impact. This study aimed to evaluate the psychometric properties of the Fear of COVID-19 (FCV-19) Scale originally developed by Ahorsu et al. (2020). A sample of 1,060 K to 12 professional teachers from Mindanao, Philippines were selected to participate in the online survey. The preliminary analysis showed a high level of perceived fear of COVID-19 in the respondents of this study. The results of the series of tests are encouraging as the FCV-19 Scale generated a robust construct validity for both one- and two- factor structure models and a very high internal consistency complemented by strong inter-item correlations and item-total correlations. The results further supported the concurrent validity of the FCV-19 Scale with selected COVID-19-related characteristics significantly predicting fear of COVID-19. Overall, this paper provides an assessment of the fear of COVID-19 in a sample of professional teachers and the properties of the FCV-19 Scale in a particular context. The FCV-19 Scale, a seven-item scale, is a valid and reliable measure that can be used to assess the fear of COVID-19 of Filipino teachers.La crisis mundial de la enfermedad del coronavirus 2019 (COVID-19) ha inducido enormemente impactos psicológicos en los humanos como el miedo. Teniendo en cuenta esta preocupación particular, existe la necesidad de probar los instrumentos utilizados para medir dicho impacto psicológico. Este estudio tuvo como objetivo evaluar las propiedades psicométricas de la Escala Miedo a COVID-19 (FCV-19) desarrollada originalmente por Ahorsu et al. (2020). Se seleccionó una muestra de 1.060 profesores profesionales de K a 12 de Mindanao, Filipinas, para participar en la encuesta en línea. El análisis preliminar mostró un alto nivel de miedo percibido a COVID-19 en los encuestados de este estudio. Los resultados de la serie de pruebas son alentadores ya que la Escala FCV-19 generó una validez de constructo robusta para modelos de estructura de uno y dos factores y una consistencia interna muy alta complementada por fuertes correlaciones entre ítems y correlaciones ítem-total. Los resultados respaldaron aún más la validez concurrente de la escala FCV-19 con características seleccionadas relacionadas con COVID-19 que predicen significativamente el miedo al COVID-19. En general, este artículo proporciona una evaluación del miedo al COVID-19 en una muestra de profesores profesionales y las propiedades de la Escala FCV-19 en un contexto particular. La escala FCV-19, una escala de siete ítems, es una medida válida y confiable que puede usarse para evaluar el miedo al COVID-19 de los maestros filipinos

A latent class analysis of cannabis use products in a general population sample of adolescents and their association with paranoia, hallucinations, cognitive disorganisation and grandiosity

Adolescents have access to a wide range of cannabis products with patterns of use becoming increasingly diverse. This study aimed to identify subgroups of adolescents in the general population who use similar types of cannabis and their association with psychotic experiences. Data on cannabis use were obtained from 467 adolescents aged between 16 and 17 years. Latent class analysis (LCA) identified groups of adolescents based on the type of cannabis used in the past 12 months. Univariate analysis explored differences in socio-demographics, substance use and mental health symptoms between groups. Multivariate analysis examined associations between class membership and psychotic experiences controlling for frequency and amount of cannabis. Finally, we explored the association between motives for cannabis and class membership using multi-nominal logistic regression. LCA identified 3 classes of adolescents: (i) herbal only (47.9%); (ii) skunk only (20.8%) and (3) mixed use (31.3%). Relative to non-users, skunk only use was associated with a 2-fold increase in paranoia (OR = 2.45, 95% CI = 1.29-4.63), along with, sleep disturbance and anxiety. Monthly cannabis use and consuming 2 or more joints on one occasion was associated with a 2-fold increase in hallucinations (OR = 2.2; 95% CI = 1.0-4.8 and OR = 1.9; 95% CI = 1.2-3.2), but did not reach the Bonferroni corrected p-value. Expansion and conformity motives differentiated the mixed cannabis class from the herbal only class. The findings suggest that different subgroups of cannabis users exist in adolescence as defined by the type of cannabis consumed and are differentially related to psychotic experiences and motives for use.</p

A latent class analysis of cannabis use products in a general population sample of adolescents and their association with paranoia, hallucinations, cognitive disorganisation and grandiosity

Adolescents have access to a wide range of cannabis products with patterns of use becoming increasingly diverse. This study aimed to identify subgroups of adolescents in the general population who use similar types of cannabis and their association with psychotic experiences. Data on cannabis use were obtained from 467 adolescents aged between 16 and 17 years. Latent class analysis (LCA) identified groups of adolescents based on the type of cannabis used in the past 12 months. Univariate analysis explored differences in socio-demographics, substance use and mental health symptoms between groups. Multivariate analysis examined associations between class membership and psychotic experiences controlling for frequency and amount of cannabis. Finally, we explored the association between motives for cannabis and class membership using multi-nominal logistic regression. LCA identified 3 classes of adolescents: (i) herbal only (47.9%); (ii) skunk only (20.8%) and (3) mixed use (31.3%). Relative to non-users, skunk only use was associated with a 2-fold increase in paranoia (OR = 2.45, 95% CI = 1.29-4.63), along with, sleep disturbance and anxiety. Monthly cannabis use and consuming 2 or more joints on one occasion was associated with a 2-fold increase in hallucinations (OR = 2.2; 95% CI = 1.0-4.8 and OR = 1.9; 95% CI = 1.2-3.2), but did not reach the Bonferroni corrected p-value. Expansion and conformity motives differentiated the mixed cannabis class from the herbal only class. The findings suggest that different subgroups of cannabis users exist in adolescence as defined by the type of cannabis consumed and are differentially related to psychotic experiences and motives for use.</p

Miedo al COVID-19 y agotamiento de la Enseñanza online en los Maestros Filipinos (Infantil-12 años)

The COVID-19 crisis practically magnified the normal fear of people, bringing other negative psychological outcomes such as job burnout. Building on this assumption, this paper aimed to compare fear of COVID-19 and remote teaching burnout across sample characteristics and relate fear of COVID-19 to the remote teaching burnout. Following comparative and correlational research designs, a sample of 1069 K to 12 Filipino teachers was selected to participate in the online survey. The data were analyzed using descriptive and inferential statistics. The results showed that the teachers have a high level of fear of COVID-19 and a moderate level of remote teaching burnout. Furthermore, COVID-19 fear of teachers did not significantly differ across all sample characteristics tested; however, remote teaching burnout significantly differed across age, monthly income, educational attainment, and teaching experience, except gender. It was further revealed that there is a positive and moderate significant relationship between fear of COVID-19 and remote teaching burnout. This linear association implies that as fear of COVID-19 of teachers increases, their remote teaching burnout also increases. Considering the current persistence of COVID-19 cases and the role of teachers in the anticipated recovery phase of education, the results of the study indicate the urgent attention of education authorities to develop measures to address the needs of teachers who may have psychological issues brought by fear of COVID-19 and remote teaching burnout.La crisis de COVID-19 prácticamente magnificó el miedo normal de las personas, trayendo más resultados psicológicos negativos como el agotamiento laboral. Partiendo de esta suposición, este documento tuvo como objetivo comparar el miedo al COVID-19 y el agotamiento de la enseñanza remota a través de las características de la muestra y relacionar el miedo al COVID-19 con el agotamiento de la enseñanza remota. Siguiendo diseños de investigación comparativos y correlacionales, se seleccionó una muestra de 1069 profesores filipinos (infantil-12 años)para participar en la encuesta en línea. Los datos se analizaron mediante estadística descriptiva e inferencial. Los resultados mostraron que los docentes tienen un alto nivel de miedo al COVID-19 y un nivel moderado de agotamiento de la enseñanza a distancia. Además, el miedo de COVID-19 a los maestros no difirió significativamente en todas las características de la muestra evaluadas; sin embargo, el agotamiento de la enseñanza a distancia difirió significativamente según la edad, los ingresos mensuales, el nivel educativo y la experiencia docente, excepto el género. Además, se reveló que existe una relación significativa positiva y moderada entre el miedo al COVID-19 y el agotamiento de la enseñanza a distancia. Esta asociación lineal implica que a medida que aumenta el miedo al COVID-19 de los docentes, también aumenta el desgaste de la enseñanza a distancia. Considerando la actual persistencia de los casos de COVID-19 y el papel de los docentes en la fase de recuperación anticipada de la educación, los resultados del estudio indican la atención urgente de las autoridades educativas para desarrollar medidas para atender las necesidades de los docentes que puedan tener problemas psicológicos planteados por miedo al COVID-19 y al agotamiento de la enseñanza a distancia.Universidad Pablo de Olavid

Genotype/phenotype correlations in AARS-related neuropathy in a cohort of patients from the United Kingdom and Ireland.

Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy with heterogeneous clinical presentation and genetic background. The axonal form (CMT2) is characterised by decreased action potentials indicating primary axonal damage. The underlying pathology involves axonal degeneration which is supposed to be related to axonal protein dysfunction caused by various gene mutations. The overlapping clinical manifestation of CMT2 with distal hereditary motor neuropathy (dHMN) and intermediate CMT causes further diagnostic difficulties. Aminoacyl-tRNA synthetases have been implicated in the pathomechanism of CMT2. They have an essential role in protein translation by attaching amino acids to their cognate tRNAs. To date six families have been reported worldwide with dominant missense alanyl-tRNA synthetase (AARS) mutations leading to clinically heterogeneous axonal neuropathies. The pathomechanism of some variants could be explained by impaired amino acylation activity while other variants implicating an editing defect need to be further investigated. Here, we report a cohort of six additional families originating from the United Kingdom and Ireland with dominant AARS-related neuropathies. The phenotypic manifestation was distal lower limb predominant sensorimotor neuropathy but upper limb impairment with split hand deformity occasionally associated. Nerve conduction studies revealed significant demyelination accompanying the axonal lesion in motor and sensory nerves. Five families have the c.986G>A, p.(Arg329His) variant, further supporting that this is a recurrent loss of function variant. The sixth family, of Irish origin, had a novel missense variant, c.2063A>G, p.(Glu688Gly). We discuss our findings and the associated phenotypic heterogeneity in these families, which expands the clinical spectrum of AARS-related neuropathies

Stroke Prevention With Left Atrial Appendage Closure in Patients With Atrial Fibrillation and Prior Intracranial Hemorrhage

BACKGROUND Oral anticoagulation (OAC) is deemed a relative contraindication after intracranial hemorrhage (ICH) if the cause cannot be eliminated and the risk of recurrence is high. That leaves atrial fibrillation (AF) patients at high risk of thromboembolic events. Endovascular left atrial appendage closure (LAAC) can be an alternative to OAC for patients requiring stroke prevention. METHODS We performed a retrospective single-centre analysis of 138 consecutive ICH patients with nonvalvular AF and high stroke risk who underwent LAAC between 2010 and 2022 at Vancouver General Hospital. We report the baseline characteristics, procedural results, and follow-up data, comparing the observed stroke/transient ischemic attack (TIA) rate with the predicted event rate based on their CHA$_{2}$DS$_{2}$-VASc scores. RESULTS The average age was 76.1 ± 8.5 years; the mean CHA$_{2}$DS$_{2}$-VASc score was 4.4 ± 1.5; and the mean HAS-BLED score was 3.7 ± 0.9. The procedural success rate was 98.6%, and the complication rate was 3.6% with no periprocedural death, stroke, or TIA. The antithrombotic regimen post-LAAC consisted of short-term dual antiplatelet therapy (1-6 months) followed by aspirin alone for a minimum of 6 months in 86.2%. At mean follow-up of 14.7 ± 13.7 months, 9 deaths (6.5%, 7 cardiovascular, 2 noncardiovascular), 2 strokes (1.4%), and 1 TIA (0.7%) had occurred. The annualized observed stroke/TIA rate was 1.8%, which was lower than the adjusted predicted stroke rate of 7.0% (95% confidence interval: 4.8%-9.2%). Two patients (1.5%) suffered another ICH (both on aspirin monotherapy). One device-related thrombus (0.7%) was confirmed and treated with OAC without sequelae. CONCLUSION Endovascular LAAC is a feasible alternative to OAC for stroke prevention in patients with nonvalvular AF and prior ICH

Common schizophrenia alleles are enriched in mutation-intolerant genes and maintained by background selection

Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide such insight. We report the largest single cohort genome-wide association study of schizophrenia (11,260 cases and 24,542 controls) and through meta-analysis with existing data we identify 50 novel GWAS loci. Using gene-wide association statistics we implicate an additional set of 22 novel associations that map onto a single gene. We show for the first time that the common variant association signal is highly enriched among genes that are intolerant to loss of function mutations and that variants in these genes persist in the population despite the low fecundity associated with the disorder through the process of background selection. Associations point to novel areas of biology (e.g. metabotropic GABA-B signalling and acetyl cholinesterase), reinforce those implicated in earlier GWAS studies (e.g. calcium channel function), converge with earlier rare variants studies (e.g. NRXN1, GABAergic signalling), identify novel overlaps with autism (e.g. RBFOX1, FOXP1, FOXG1), and support early controversial candidate gene hypotheses (e.g. ERBB4 implicating neuregulin signalling). We also demonstrate the involvement of six independent central nervous system functional gene sets in schizophrenia pathophysiology. These findings provide novel insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation intolerant genes and suggest a mechanism by which common risk variants are maintained in the population

GPCRomics : GPCR Expression in Cancer Cells and Tumors Identifies New, Potential Biomarkers and Therapeutic Targets

Financial support for these studies was provided by Roche, the Lymphoma and Leukemia Society, Friends of ANCHOR, an ASPET Astellas Award and grants from the National Institutes of Health, National Cancer Institute (CA189477, CA121938, CA155620). National Cancer Institute (NCI) Therapeutic Training Grant 5T32CA121938, NIH/NCI Research Grants R21 CA189477, an ASPET David Lehr Award and the Padres Pedal the Cause #PTC2017 award.Peer reviewedPublisher PD

A randomized controlled trial of tenecteplase versus standard of care for minor ischemic stroke with proven occlusion (TEMPO-2): rational and design of a multicenter, randomized open-label clinical trial

Background: Almost half of acute ischemic stroke patients present with mild symptoms and there are large practice variations in their treatment globally. Individuals with an intracranial occlusion who present with minor stroke are at an increased risk of early neurological deterioration and poor outcomes. Individual patient data meta-analysis in the subgroup of patients with minor deficits showed benefit of alteplase in improving outcomes; however, this benefit has not been seen with intravenous alteplase in published randomized trials. Design: TEMPO-2 (A Randomized Controlled Trial of Tenecteplase Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion) is a prospective, open label with blinded outcome assessment, randomized controlled trial, designed to test the superiority of intravenous tenecteplase (0.25 mg/kg) over nonthrombolytic standard of care, with an estimated sample size of 1274 patients. Adult patients presenting with acute ischemic stroke with the National Institutes of Health Stroke Scale (NIHSS) ⩽ 5 and visible arterial occlusion or perfusion deficit within 12 h of onset are randomized to receive either tenecteplase (0.25 mg/kg) or standard of care. The primary outcome is return to baseline neurological functioning, measured by the modified Rankin scale (mRS) at 90 days. Safety outcomes include death and symptomatic hemorrhage (intra or extra-cranial). Other secondary outcomes include mRS 0–1, mRS 0–2, ordinal shift analysis of the mRS, partial, and full recanalization on follow-up computed tomography angiogram. Conclusion: Results of this trial will aid in determining whether there is benefit of using tenecteplase (0.25 mg/kg) in treating patients presenting with minor stroke who are at high risk of developing poor outcomes due to presence of an intracranial occlusion