Aberrant Behavior Research Articles

Neurotransmitter acetylcholine mediates the mummification of Ophiocordyceps sinensis-infected Thitarodes xiaojinensis larvae.

Parasites can manipulate host behavior to facilitate parasite transmission. One such host-pathogen interaction occurs between the fungus Ophiocordyceps sinensis and the ghost moth Thitarodes xiaojinensis. O. sinensis is involved in the mummification process of infected host larvae. However, the underlying molecular and chemical mechanism for this phenomenon is unknown. We characterized the small molecules regulating host behaviors and the altered metabolites in infected and mummified host larvae. Lipid-related metabolites, such as phosphatidylcholine, were identified in infected and mummified larvae. Decreased levels of the neurotransmitter acetylcholine (ACh) and elevated choline levels were observed in the brains of both the infected and mummified larvae. The aberrant activity of acetylcholinesterase (AChE) and relative mRNA expression of ACE2 (acetylcholinesterase) may mediate the altered transformation between ACh and choline, leading to the brain dysfunction of mummified larvae. Caspofungin treatment inhibited the mummification of infected larvae and the activity of AChE. These findings indicate the importance of ACh in the mummification of host larvae after O. sinensis infection.IMPORTANCEOphiocordyceps sinensis-infected ghost moth larvae are manipulated to move to the soil surface with their heads up in death. A fruiting body then grows from the caterpillar's head, eventually producing conidia for dispersal. However, the underlying molecular and chemical mechanism has not been characterized. In this study, we describe the metabolic profile of Thitarodes xiaojinensis host larvae after O. sinensis infection. Altered metabolites, particularly lipid-related metabolites, were identified in infected and mummified larvae, suggesting that lipids are important in O. sinensis-mediated behavioral manipulation of host larvae. Decreased levels of the neurotransmitter acetylcholine were observed in both infected and mummified larvae brains. This suggests that altered or reduced acetylcholine can mediate brain dysfunction and lead to aberrant behavior. These results reveal the critical role of acetylcholine in the mummification process of infected host larvae.

Exposure to low (10 cGy) doses of 4He ions leads to an apparent increase in risk taking propensity in female rats

The planned missions to the Moon and Mars will present more significant health challenges to astronauts compared to low earth orbit missions. During deep space missions, astronauts will be constantly exposed to Space radiation (SR). Multiple rodent studies suggest that < 25 cGy of SR impairs performance in executive functions, which play a key role in advanced cognitive processes, but also regulate response inhibition and impulse control. There is the possibility that SR exposure may exacerbate aberrant behaviors evoked by psychological stress related to exposure to isolated and confined (ICE) hostile environment or independently induce additional aberrant behaviors. This study has determined that female Wistar rats exposed to 10 cGy of 250 MeV/n He had an increased risk taking propensity (RTP)\\compared to shams. The increased RTP of the He-exposed rats was associated with significantly increased reaction times during the trials, suggesting a SR-induced loss of processing speed. The response times of the He-exposed rats were even further reduced in trials that immediately followed a loss, raising the possibility that conflict and interference avoidance may be impaired after SR exposure. Whether these findings occur following other types of SR exposure, and/or in male rats remains to be determined.

Factors Associated with an Increased Risk of Opioid Misuse Among Patients with Non-Cancer Pain in Malaysian Pain Clinic Settings

ABSTRACT This study examined the factors associated with a high risk of opioid misuse among patients receiving opioid treatment for their non-cancer pain in Malaysian pain clinics. The Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R), a validated instrument for predicting the risk of aberrant drug-related behaviors, were used as a proxy to indicate risk of opioid misuse. Data analysis was stratified into high-risk and low-risk patient groups. Patient factors assessed included pain intensity, pain interference with daily activities, and health-related quality of life. Prescription opioid exposure was examined via patient medical and prescription records review. Among the 61 patients recruited, 62.3% scored ≥18 on the SOAPP-R, which indicates a high risk for opioid misuse. Factors associated with a high risk of opioid misuse were found to be high level of pain interference with daily activities, poorer mental health, and younger age. High-risk patients were found to be prescribed a lower mean daily opioid dose of <20 mg/day compared to low-risk patients (20–49 mg/day). This highlights the need for further research to distinguish aberrant drug-related behaviors due to inadequate pain management from that of actual prescription opioid misuse among non-cancer pain patients attending pain clinics.

Integrative Care for Challenging Behaviors in People with Intellectual Disabilities to Reduce Challenging Behaviors and Inappropriate Psychotropic Drug Prescribing Compared with Care as Usual: A Cluster-Randomized Trial.

People with intellectual disabilities (IDs) often present with challenging behaviors (CBs) mostly due to inappropriate environments and mental and physical disorders. Integrative care is recommended to address CBs. However, in clinical practice, psychotropic drugs are often prescribed off-label for CBs, although the effectiveness is unclear, and side effects frequently occur. We conducted a cluster-randomized controlled study to investigate the effect of integrative care provided by a collaboration of an ID specialized mental healthcare team and participants' own ID service providers' care team on reducing CBs and inappropriate off-label psychotropic drug prescriptions compared with care as usual. Participants (N = 33, aged 19-81 years) had a moderate, severe, or profound intellectual disability and used off-label psychotropic drugs. The primary outcome measures were the Aberrant Behavior Checklist and the total dose of psychotropic drug prescriptions. At the study endpoint of 40 weeks, we found no effect of the intervention on the total ABC score and on the total dose of psychotropic drug prescriptions. In the intervention group, however, the psychotropic drug dose decreased significantly, while CBs did not change. The small sample size and not-completed interventions due to organizational problems may have affected our findings. This study illustrates the difficulties in the implementation of integrative care.

Preclinical studies of gene replacement therapy for CDKL5 deficiency disorder

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a rare neurodevelopmental disorder caused by a mutation in the X-linked CDKL5 gene. CDKL5 is a serine/threonine kinase that is critical for axon outgrowth and dendritic morphogenesis as well as synapse formation, maturation, and maintenance. This disorder is characterized by early-onset epilepsy, hypotonia, and failure to reach cognitive and motor developmental milestones. Because the disease is monogenic, delivery of the CDKL5 gene to the brain of patients should provide clinical benefit. To this end, we designed a gene therapy vector, adeno-associated virus (AAV)9.Syn.hCDKL5, in which human CDKL5 gene expression is driven by the synapsin promoter. In biodistribution studies conducted in mice, intracerebroventricular (i.c.v.) injection resulted in broader, more optimal biodistribution than did intra-cisterna magna (i.c.m.) delivery. AAV9.Syn.hCDKL5 treatment increased phosphorylation of EB2, a bona fide CDKL5 substrate, demonstrating biological activity invivo. Our data provide proof of concept that i.c.v. delivery of AAV9.Syn.hCDKL5 to neonatal male Cdkl5 knockout mice reduces pathology and reduces aberrant behavior. Functional improvements were seen at doses of 3e11 to 5e11 vector genomes/g brain, which resulted in transfection of ≥50% of the neurons. Functional improvements were not seen at lower doses, suggesting a requirement for broad distribution for efficacy.

A deterministic, c-di-GMP-dependent program ensures the generation of phenotypically similar, symmetric daughter cells during cytokinesis

Phenotypic heterogeneity in bacteria can result from stochastic processes or deterministic programs. The deterministic programs often involve the versatile second messenger c-di-GMP, and give rise to daughter cells with different c-di-GMP levels by deploying c-di-GMP metabolizing enzymes asymmetrically during cell division. By contrast, less is known about how phenotypic heterogeneity is kept to a minimum. Here, we identify a deterministic c-di-GMP-dependent program that is hardwired into the cell cycle of Myxococcus xanthus to minimize phenotypic heterogeneity and guarantee the formation of phenotypically similar daughter cells during division. Cells lacking the diguanylate cyclase DmxA have an aberrant motility behaviour. DmxA is recruited to the cell division site and its activity is switched on during cytokinesis, resulting in a transient increase in the c-di-GMP concentration. During cytokinesis, this c-di-GMP burst ensures the symmetric incorporation and allocation of structural motility proteins and motility regulators at the new cell poles of the two daughters, thereby generating phenotypically similar daughters with correct motility behaviours. Thus, our findings suggest a general c-di-GMP-dependent mechanism for minimizing phenotypic heterogeneity, and demonstrate that bacteria can ensure the formation of dissimilar or similar daughter cells by deploying c-di-GMP metabolizing enzymes to distinct subcellular locations.

Effectiveness of pharmacological interventions for managing ADHD symptoms in individuals with autism spectrum disorder: A systematic review and meta-analysis

ObjectivesThis systematic review sought to provide evidence for the effectiveness of common pharmacological interventions used for treating attention deficit hyperactivity disorder (ADHD) symptoms in the autism spectrum disorder (ASD) population, considering studies attempting to find safe and effective drugs. MethodsWe searched for randomized controlled trials describing the effectiveness and/or safety profile of pharmacological interventions for treating ASD and ADHD or ASD with ADHD symptoms using three bibliographic databases: PubMed, Cochrane Library, and Embase. We have chosen ADHD symptoms measured by any clinical scale as the primary outcome. As additional outcomes, we have used other symptoms of aberrant behavior measured by the aberrant behavior checklist, satisfaction with treatment, and peer satisfaction. ResultsTwenty-two publications met the inclusion criteria for the systematic review and eight for the meta-analysis. In our investigation, we found a few articles using clonidine, modafinil, and bupropion as interventions when compared to methylphenidate (MPH). Our meta-analysis showed that MPH had positive changes compared to placebo in symptoms such as hyperactivity, irritability, or inattention. However, no effect was found in stereotyped symptoms, and our data's quantitative analysis revealed a large effect of MPH-induced adverse effects on the dropout rate. On the other hand, atomoxetine initiation had positive effects when compared to placebo on symptoms of hyperactivity and inattention. We have found no effect of atomoxetine on stereotypes or irritability. Furthermore, atomoxetine did not influence side effects that caused dropouts from studies. ConclusionOur results indicated that atomoxetine has a modest effect on hyperactivity and inattention symptoms, with a relatively benign profile of side effects. MPH appears to be effective in handling hyperactivity, inattention, and irritability symptoms. However, our results on atomoxetine revealed increased dropouts due to adverse effects when compared to MPH or placebo. Evidence for other substances such as guanfacine, clonidine, bupropion, or modafinil is either preliminary or nonexistent.

Leaving Against Medical Advice: Current Problems and Plausible Solutions.

Leave against medical advice (LAMA) is defined as 'a decision to leave the hospital before the treating physician recommends discharge', and is associated with higher rates of readmission, longer subsequent hospitalization, and worse health outcomes. In addition to this, they also contribute to poor healthcare resource utilization. We conducted a single-center audit to establishpatient demographics and contributing factors of patients leaving against medical advice from our emergency department (ED). We benchmarked our data against locally available clinical policy guidelines.We interrogated our electronic health record system (known as Salamtak®), which is a Cerner-based platform (Cerner Corporation, Kansas City, MO 64138)for patients who signed LAMA from ED from 2018 to 2023. We selected a convenience pilot sample of 120 subjects. Based on a literature review, we identified patient demographics (age, gender, nationality, socioeconomic status, marital status, religion), possible contributing factors (time of attendance, insurance status, length of ED stay), and patient outcomes (reattendances within 1 week and mortality) to evaluate. Based on locally available guidance, we formulated six criteria to audit with a standard set at 100% for each. A team of emergency medicine residents collected data that was anonymized on an Excel spreadsheet (Microsoft Excel,Microsoft Corporation. (2018). Basic descriptive statistics were used to collate results. About 93 patients (77.5%) were 16 years and above, and 27 patients (22.5%) were below 16 years. There was a slight preponderance of males (64 patients, 53.3%) than females (56 patients, 46.6%). The majority of LAMA cases presented in the evening and night (97 patients, 80.8%). About 57 (47.5%) patients had an ED length of stay of 3 hours or more. The average ED length of stay for these patients was 3.4 hours. About 73 patients (60.3%) were insured. Out of 120 patients, only 12 (10%) had a mental capacity assessment documented. The commonest reason for signing LAMA was a social reason in 45 (37.5%) cases. In the remaining cases, the causes were a combination of family, financial, waiting, or other/undocumented reasons). When faced with a decision to LAMA, the involvement of a Public Relationship Officer (PRO) was only documented to be consulted in seven (5.8%) cases. About 14 cases were re-attended within 1 week (11.6%) and no mortalities were reported in any of the reattendances. LAMA is a not-so-rare phenomenon often occurring in EDs, and often a cause of trepidation for healthcare workers. Treating this as an aberrant behavior on the part of the patient, or laying the responsibility for this action on the healthcare provider is primitive, counter-productive, and not patient-centric. Familiarity with local guidelines around this contentious area is essential. Revised nomenclature like 'premature discharge' may be less stigmatizing for the patient.Where possible, a harm reduction approach should be used and frontline healthcare workers must be prepared with an escalation plan.In the United Arab Emirates, familiarity with Wadeema's Law as a child protection measure is essential.

α7nAChR-mediated astrocytic activation: A novel mechanism of Xiongzhi Dilong decoction in ameliorating chronic migraine

Ethnopharmacological relevanceAlpha 7 nicotinic acetylcholine receptor (α7nAChR)-mediated astrocytic activation is closely related to central sensitization of chronic migraine (CM). Xiongzhi Dilong decoction (XZDL), originated from Xiongzhi Shigao decoction of Yi-zong-jin-jian, has been confirmed to relieve CM in experiment and clinic. However, its underlying mechanism for treating CM has not been elucidated. Aim of the studyTo reveal the underlying mechanisms of XZDL to alleviate CM in vivo focusing mainly on α7nAChR-mediated astrocytic activation and central sensitization in TNC. Materials and methodsCM rat model was established by subcutaneous injection of nitroglycerin (NTG) recurrently, and treated with XZDL simultaneously. Migraine-like behaviors of rats (ear redness, head scratching, and cage climbing) and pain-related reactions (mechanical hind-paw withdrawal threshold) of rats were evaluated before and after NTG injection and XZDL administration at different points in time for nine days. The immunofluorescence single and double staining were applied to detect the levels of CGRP, c-Fos, GFAP and α7nAChR in NTG-induced CM rats. ELISA kits were employed to quantify levels of TNF-α, IL-1β, and IL-6 in medulla oblongata of CM rats. The expression levels of target proteins were examined using western blotting. Finally, methyllycaconitine citrate (MLA, a specific antagonist of α7nAChR) was applied to further validate the mechanisms of XZDL in vivo. ResultsXZDL significantly attenuated the pain-related behaviors of the NTG-induced CM rats, manifesting as constraints of aberrant migraine-like behaviors including elongated latency of ear redness and decreased numbers of head scratching and cage climbing, and increment of mechanical withdrawal threshold. Moreover, XZDL markedly lowered levels of CGRP and c-Fos, as well as inflammatory cytokines (IL-1β, IL-6 and TNF-α) in CM rats. Furthermore, XZDL significantly enhanced α7nAChR expression and its co-localization with GFAP, while markedly inhibited the expression of GFAP and the activation of JAK2/STAT3/NF-κB pathway in the TNC of CM rats. Finally, blocking α7nAChR with MLA reversed the effects of XZDL on astrocytic activation, central sensitization, and the pain-related behaviors in vivo. ConclusionXZDL inhibited astrocytic activation and central sensitization in NTG-induced CM rats by facilitating α7nAChR expression and suppressing JAK2/STAT3/NF-κB pathway, implying that the regulation of α7nAChR-mediated astrocytic activation represents a novel mechanism of XZDL for relieving CM.

Modeling Fragile X Syndrome: Characterizing Fmr1 Gene Knockout Mice across Genotype, Behavior, and Morphology

ABSTRACT Objective: Fragile X syndrome (FXS) is a hereditary condition resulting from dynamic mutations in the Fmr1 gene, leading to reduced or absent fragile X mental retardation protein (FMRP). Although molecular genetic diagnostics for FXS have advanced, there is currently a lack of effective clinical treatment. Hence, identifying a suitable FXS animal model is crucial for FXS therapeutic studies. This study primarily aims to evaluate whether Fmr1 mice display aberrant behaviors similar to those observed in human FXS patients, aiming to validate their feasibility as a model for FXS. Research Design and Methods: Polymerase chain reaction and immunoblotting were employed to genotype Fmr1 knockout (KO) mice and wild-type (WT) mice. Using hematoxylin and eosin staining and Golgi staining, testicular and dendritic spine morphology in both animal groups was observed. The animals were subjected to audiogenic seizure (AGS) observation, evaluating their learning and memory levels using the water maze and light avoidance methods, while their exploratory behavior capacity was assessed using the open-field and autonomous activity experiments. Anxiety behavior was evaluated using the elevated plus maze. Results: WT mice produced a 500 bp DNA fragment, while KO mice yielded an 800 bp fragment. KO mice exhibited a lack of FMRP expression, notably increased dendritic spine length and density, and presented with macroorchidism. KO mice showed increased susceptibility to AGS. In the Morris water maze experiment, KO mice displayed significantly increased escape latency and platform crossings. The spatial search experiment revealed that KO mice spent significantly less time in the target quadrant compared to WT mice. The light-avoidance and platform experiments indicated a significant reduction in latency for KO mice but an increase in errors. In the open-field experiment, KO mice spent significantly more time and made more entries into the central zone compared to WT mice. KO mice exhibited increased total travel distance and speed. The elevated plus maze experiment showed that KO mice spent significantly more time, made more entries, and traveled further in the open area compared to WT mice. The autonomous activity experiment revealed that KO mice had significantly more activity counts than WT mice but fewer standing counts. Conclusions: Findings from genotype, protein expression spectrum, morphology, and behavioral results suggest that Fmr1 gene KO mice demonstrate phenotypes similar to those observed in human FXS, making them a potential model for future FXS research. These phenotypes are associated with the absence of FMRP expression.

Burden and Coping Strategies of Hypoglycemia in People with Diabetes.

Hypoglycemia is a limiting adverse effect of glucose-lowering medications and particularly insulin replacement therapy. This review provides insights into the burden of hypoglycemia in the management of diabetes and outlines strategies available to reduce the risk of hypoglycemia and improve patients' well-being. People with type 1 diabetes are primarily affected by hypoglycemic episodes which are associated with direct physical harms like injuries and cardiac events as well as indirect psychosocial consequences including constant anxiety, absenteeism, increased healthcare costs and overall poorer quality of life. These complications are more prominent amongst individuals with hypoglycemia unawareness or overnight hypoglycemia and could even extend to caregivers such as parents of children with diabetes. Patients experiencing frequent or severe hypoglycemic events might also develop a pathological fear of hypoglycemia and adopt aberrant behaviors intending to maintain higher blood glucose levels. Modern pharmaceutical options with a safer profile in terms of hypoglycemia are available including novel basal insulins with lower rates of nocturnal hypoglycemia along with ultra-rapid-acting insulin analogs with a shorter duration of action that might avert late post-meal hypoglycemia. Continuous glucose monitoring and sensor-augmented insulin pump therapy with low glucose suspend technology can also prevent hypoglycemia, although concerns about cost and patient satisfaction remain. Advancements in insulin therapy and technological modalities should be coupled with ongoing education and support for patients to become co-managers of their disease and reduce the risk of hypoglycemia.

Homing of translocated native Indian pythons in Moyar River Valley, South India

Homing is often a critical aspect of an animal's behavioural and spatial ecology. Translocation is considered to be a wildlife management strategy that could reduce human-wildlife confrontation, but this strategy may not be effective if animals attempt to home to their original capture location. Translocation of animals from sites where possible human-wildlife interaction occurs is a widespread but controversial intervention to resolve conflicts. In India, snakes are often the subject of such translocations, but there is a paucity of information on the behaviour of translocated snakes compared to resident snakes. The Indian python (Python molurus), one of the largest carnivores in the Indian subcontinent, is classified as Near Threatened by the IUCN. We conducted a two-year radio-tracking study (December 2018 to December 2020) on the movements of 14 adult Indian pythons in the Moyar River Valley, within the Sathyamangalam and Mudumalai Tiger Reserves. Eleven of the 14 pythons were translocated 0.28–55.7 kms from their capture locations, while 3 pythons were not translocated: 6 were translocated short distances (<5 km from capture; range 0.28–4.67 kms), 2 were translocated to medium distances (9–11 kms from capture location), and 3 were translocated to long distances (21–55.7 kms from capture location). Four of the six snakes translocated short distances all returned to within 500 m of their original capture locations, and all 6 returned over 60 % of the translocated distance to the initial capture location. Of the two snakes translocated medium distances, both returned to within 1.1 km of the capture location (∼90 % of the distance home). None of the three snakes that were translocated long distances successfully returned to their capture locations. Translocated pythons exhibited greater net movement distances than resident snakes within the first 2 months of release. Based on these results, long-distance translocation may be an effective strategy to minimize human-python conflict, while short or medium distance translocation is unlikely to be successful. However, more research is needed about the long-term survival of translocated snakes as well as soft-release methodologies that could prevent aberrant movement behaviour directly following release.

Effect of probiotics on children with autism spectrum disorders: a meta-analysis

BackgroundResearches have found that alteration of intestinal flora may be closely related to the development of autism spectrum disorder (ASD). However, whether probiotics supplementation has a protective effect on ASD remains controversial. This meta-analysis aimed to analyze the outcome of probiotics in the treatment of ASD children.MethodsThe Pubmed, Cochrane Library, Web of Science and Embase were searched until Sep 2022. Randomized controlled trials (RCTs) relevant to the probiotics and placebo treatment on ASD children were screened. Quality assessment of the included RCTs was evaluated by the Cochrane collaboration’s tool. The primary outcomes were ASD assessment scales, including ABC (aberrant behavior checklist) and CBCL (child behavior checklist) for evaluating the behavior improvement, SRS (social responsiveness scale) for social assessment, DQ (developmental quotient) for physical and mental development and CGI-I (clinical global impression improvement) for overall improvement. The secondary outcome was total 6-GSI (gastrointestinal severity index).ResultsIn total, 6 RCTs from 6 studies with 302 children were included in the systemic review. Total 6-GSI (MD=-0.59, 95%CI [-1.02,-0.17], P < 0.05) decreased significantly after oral administration of probiotics. Whereas, there was no statistical difference in ABC, CBCL, SRS, DQ and CGI-I between probiotics and placebo groups in ASD children.ConclusionProbiotics treatment could improve gastrointestinal symptoms, but there was no significant improvement in ASD.

Sleep and aberrant eating behaviors in metabolic/bariatric presurgical candidates

BackgroundMetabolic/bariatric surgery (MBS) is the most effective treatment for obesity, yet many factors influence successful individual weight loss. Among those are a variety of health behaviors that are assessed in the process of presurgical psychological evaluations, including eating pathology and sleep disturbance (both of which are relatively common among surgical candidates). ObjectivesThis study aims to examine the relationship between sleep, binge eating, and night eating behaviors among individuals seeking MBS. SettingMedical center and private psychological practice in Mississippi. MethodsPatients (N = 311) seeking presurgical psychological evaluations for bariatric surgery completed self-report measures. Of these, 83.0% were females and 70.7% of those with ethnicity data identified as White. Average body mass index (BMI) in the sample was 46.5 (standard deviation [SD] = 8.02). Correlations between variables were calculated and examination of the indirect effect of sleep disturbance on night eating as mediated by binge eating was conducted. ResultsSleep disturbance, binge eating, and night eating were significantly associated (b = .22–.45). Mediation analysis yielded a significant indirect effect, indicating that binge eating propensity explains the relationship between impaired sleep and night eating symptoms (b = .09, standard error [SE] = .03, confidence interval [CI]: .04–.18). ConclusionsThe observed relationship between sleep disturbance, night eating, and binge eating among bariatric candidates provides implications for future research and treatment approaches. Specifically, additional attention to sleep disturbance in the presurgical assessment process and consideration of sleep hygiene as a potential target for intervention may facilitate improvements in overall health, adjustment, and sustained weight loss.

Cross-Cultural Behaviors: A Comparative Analysis of Driving Behaviors in Pakistan and China

When analyzing road safety across cultural boundaries, driver behavior is a crucial component to consider. Given that driver behavior directly affects both the likelihood of accidents and the severity of their implications, it is crucial to comprehend and analyze it. The present study examined the differences in dangerous, aberrant, and positive driving behaviors across China and Pakistan. The effects of these behaviors on road traffic accidents were also considered. In the study, 1253 respondents completed a questionnaire package consisting of the Dula Dangerous Driving Index (DDDI), Aberrant Driving Behavior Questionnaire (DBQ), Positive Driving Behavior Scale (PDBS), and items related to demographics. Generalized linear models were utilized to compare and determine the factors responsible for dangerous driving behaviors. Mean scores for DBQ and PDBS items were compared. Finally, binary logistic regression models were used to find the factors responsible for traffic accidents across both countries. The results indicated that aggressive and risky driving predicted traffic accidents in both countries, followed by errors and violations, which also predicted traffic accidents significantly. Positive driving behaviors predicted accidents negatively in both samples. Furthermore, it was found that Chinese drivers compared to Pakistani drivers are less aggressive and risk-taking and commit fewer violations and errors while driving. To increase road safety in Pakistan, traffic laws must be strictly enforced uniformly, and violations must result in severe penalties, i.e., demerit points or cancellation of a driver’s license. Programs for road safety awareness and education must be expanded. Employing national culturally concentrated road safety strategies may be a more effective way to encourage safe driving behaviors.

Circ_0007611 modulates the miR-34c-5p/LPAR2 cascade to suppress proliferation and enhance apoptosis of HTR-8/SVneo cells

IntroductionThe aberrant biological behaviors of trophoblast cells actively take part in the pathogenesis of preeclampsia (PE). Herein, we defined the action of the circular RNA (circRNA) circ_0007611 on trophoblast cell apoptosis and growth to understand its role in PE. MethodsExpression of circ_0007611, miR-34c-5p and lysophosphatidic acid receptor 2 (LPAR2) mRNA was analyzed by qPCR. LPAR2 protein was determined by western blotting. Cell proliferation was analyzed by EdU assay. We assessed apoptosis through flow cytometry and analysis of caspase3 activity and apoptosis-related marker proteins. The binding of miR-34c-5p and circ_0007611 or LPAR2 was verified by dual-luciferase and pull-down assays. ResultsCirc_0007611 and LPAR2 levels were augmented, while miR-34c-5p was diminished in blood samples of PE. Circ_0007611 deficiency repressed cell apoptosis and enhanced the growth of HTR-8/SVneo cells. Circ_0007611 interacted with miR-34c-5p, and miR-34c-5p depletion reversed circ_0007611 deficiency-induced HTR-8/SVneo cell apoptotic inhibition and growth enhancement. MiR-34c-5p targeted LPAR2, and circ_0007611 affected LPAR2 expression via miR-34c-5p competition. Circ_0007611 deficiency-induced HHTR-8/SVneo cell apoptotic inhibition and growth enhancement were also counteracted by LPAR2 overexpression. DiscussionCirc_0007611 modulates the miR-34c-5p/LPAR2 cascade to enhance apoptosis and inhibit proliferation in HTR-8/SVneo cells, thereby contributing to the progression of PE.

The role of subjective risk perception and self-esteem in the relationship between sensation seeking and aberrant behaviors on the road: A moderated-moderation model

Introduction: Road crashes are still one of the main causes of death around the world. Risky behavior has been proposed as one of the foremost predictors, with the theoretical framework of aberrant behavior emerging as a predominant approach for its examination. Sensation seeking has been pointed out as one of the main personality predictors of aberrant behavior. The current research aimed to investigate the moderated-moderation effect of both risk perception and self-esteem in the relationship between sensation seeking and aberrant behavior. Method: Two studies were conducted. The first study aimed to analyze the psychometric properties of the Spanish version of the Risk Perception Scale (RPS), a 10-item self-report to assess risk perception. A sample composed of 471 Spanish drivers (319 female, Mage = 29.75) completed the RPS. In the second study, a different sample of 236 Spanish drivers (129 female, Mage = 38.49) completed a set of self-reports aiming both to analyze the concurrent and divergent validity of the RPS, and to test the main moderated-moderation hypothesis. Results: With respect to the first study, the confirmatory factor analysis (CFA) supported a 7-item version which fitted in a single reliable factor (α = .74). Regarding the second study, the results supported both the concurrent and divergent validity of the RPS. Likewise, it was verified the moderated-moderation effect in the case of ordinary violations (R2 = .34), aggressive violations (R2 = .20), and lapses (R2 = .12). Conclusions: The RPS is a useful self-report to assess subjective risk perception in Spanish drivers. Both self-esteem and risk perception affect the relationship between sensation seeking and aberrant driving behavior. Practical implications: Intervention programs aiming to reduce aberrant driving behavior should be focused on reducing sensation seeking tendencies while simultaneously enhancing both risk perception skills and self-esteem.

Robustness of Computer Adaptive Tests to the Presence of Item Preknowledge: A Simulation Study

Item preknowledge describes a scenario where candidates may have access to the some of the test items prior to the test administration. This involves the sharing of test materials and/or answers and it is difficult to identify the individuals with item preknowledge or the shared materials of test. Nevertheless, it is essential to investigate the ‘item preknowledge’ problem because it can significantly affect the validity of test results. It is believed that traditional linear tests are more robust to this type of aberrant response behavior than adaptive tests. In this context, the aim of this study is to examine the effect of item preknowledge on computer adaptive tests and to try to identify the conditions under which adaptive tests are most resistant to the item preknowledge. With this purpose, a Monte Carlo simulation study was performed and 28 different conditions were examined. The results of the study indicated the EAP estimation method provided better measurement precision than ML over all conditions. When 2PL and 3PL IRT models were compared, it was observed that 2PL had higher precision at most of the conditions. However, when the aberrancy ratio increased and reached to the 20% for both individuals and items, 3PL outperformed the 2PL model and gave the best results with the EAP combination. The results were discussed in line with literature on item preknowledge and CAT and implications for practitioners and further research were provided.

Aberrance: An R Package for Detecting Aberrant Behavior in Test Data.

aberrance: An R Package for Detecting Aberrant Behavior in Test Data.

Dangerous Variation or Patient-Centered Care? Palliative Care and Pain Providers' Comfort, Experiences, and Approaches when Treating Cancer Pain With Coexisting Aberrant Behaviors.

Patients with cancer-related pain are at high risk for aberrant drug use behaviors (ADB), including self-escalation, diversion and concurrent illicit substance or opioid misuse; however, limited evidence is available to guide opioid prescribing for patients with life-limiting illness and concurrent or suspected ADB. We sought to characterize how specialists evaluate for and manage these high-risk behaviors in patients with cancer-related pain. We conducted telephonic semi-structured interviews with palliative care and pain medicine providers. Participants discussed their own comfort and experience level with identifying and managing ADB in patients with life-limiting illness. They were subsequently presented with a series of standardized scenarios and asked to describe their concerns and management strategies. 95 interdisciplinary pain and palliative care specialists were contacted; 37 agreed to participate (38.9%). Analysis of interview contents revealed several central themes: (1) widespread discomfort and anxiety regarding safe and compassionate opioid prescribing for high-risk patients, (2) belief that widely used risk-mitigation tools such as opioid contracts and urine drug screens provided inadequate support for decision-making, and (3) lack of institutional and organizational support and guidance for safe prescribing strategies. Most clinicians reported self-education regarding addiction and alternative prescribing/pain management strategies. Providers varied widely in their willingness to discontinue opioid prescribing in a patient with aberrant behavior and pain associated with life-limiting illness. Providers caring for patients demonstrating ADB and cancer-related pain struggle to balance safe prescribing with symptom management. Increased guidance is needed regarding opioid prescribing, monitoring, and discontinuation in high-risk patients.