Adherence to prescription guidelines for medical cannabis in disability claimants.

OBJECTIVE: To examine a case series of 70 disability claimants who were referred to a clinic for multidisciplinary medical evaluation for physician compliance with cannabis prescription guidelines for pre-existing cannabis prescriptions. DESIGN: Retrospective case series analysis. SETTING: A private clinic in New Brunswick specializing in multidisciplinary medical assessment for institutional third-party insurers. PARTICIPANTS: All referrals for independent review of cannabis prescriptions between May 2016 and February 2018 (N = 70). MAIN OUTCOME MEASURES: Compliance with the cannabis prescription guidelines. RESULTS: Treating physicians were found to have not adhered to the guidelines in 53 of 61 patients (86.9%) who were prescribed cannabis products for pain management and in 8 of 9 patients (88.9%) who were prescribed cannabis products for treatment of posttraumatic stress disorder. Clinical assessment and radiologic review failed to identify a neuropathic cause of pain in 70.5% of pain cases. Adequate trials of noncannabinoid medications had not been attempted for 72.1% of patients with pain nor for any of the patients with posttraumatic stress disorder. Contraindications to cannabis were identified in 65.7% of cases, including evidence suggesting a past or present cannabis use disorder or currently active substance use disorder in 34.3% of cases. The prescriptions were found to be consistent with prescription guidelines in just 12.9% of cases. CONCLUSION: Very few of the reviewed cannabis prescriptions were found to be consistent with cannabis prescription guidelines. Respectful attention to guidelines might avoid unwarranted overprescribing, limit the secondary increase in comorbidity, and facilitate future scientific study and evaluation of medical cannabis.

Exaggerated Functional Impairment due to Malingered Neurocognitive Dysfunction Following Mild Traumatic Brain Injury.

OBJECTIVE: Functional impairment associated with Neurocognitive Disorder is often claimed in medico-legal settings after mild Traumatic Brain Injury (mTBI). This case-control study examined self-reported functional impairment and the plausibility of chronic disability claims following uncomplicated mTBI. METHOD: Independent Medical Evaluations included a battery of performance and symptom validity tests, along with self-reports of physical or emotional complaints and functional impairment. Slick and colleagues' (Slick, D. J., Sherman, E. M., & Iverson, G. L. (1999). Diagnostic criteria for malingered neurocognitive dysfunction: Proposed standards for clinical practice and research. The Clinical Neuropsychologist, 13, 545-561.) criteria ruled out probable malingering in 21 mTBI cases without psychiatric comorbidity and their self-reports were compared to those of seven non-malingering cases with a psychiatric comorbidity, 17 who were probable malingerers, and 31 orthopedic pain sufferers. Coherence Analysis of medical documentation corroborated assignment of mTBI cases to non-malingering versus probable malingering groups. RESULTS: Probable malingerers reported more postconcussion symptoms than non-malingerers (d = 0.79) but they did not differ significantly on tests of neurocognitive performance. Probable malingerers and orthopedic pain patients gave significantly higher ratings of functional impairment (d = 1.28 and 1.26) than non-malingerers. Orthopedic pain patients reported more disability due to pain than non-malingerers (d = 1.03), but pain catastrophizing was rated more highly by the probable malingerers (d = 1.21) as well as by the orthopedic pain patients (d = 0.98). The non-malingerers reported lower emotional distress than the other three groups, but only the probable malingerers reported elevated depression symptoms compared to the non-malingerers (d = 1.01). CONCLUSIONS: The combined evaluation of performance validity, function, and coherence analysis would appear to enhance the difficult clinical evaluation of postconcussion symptoms in the medical-legal setting.

Experienced EGM Players Know How to Control the Reinforcement Rate and Time on Device.

This experiment used motivational instructions to test whether experienced slot machine players are able to manipulate the frequency of winning outcomes and the time taken to deplete funds while playing a popular slot machine game. Twenty-four participants played in four conditions intended to motivate them to play the game as they normally do, to deplete funds quickly, to get a long losing streak, and to avoid getting a bonus round. Compared to how they normally play, participants significantly reduced the number of bought paylines when trying to get losing streaks or avoid bonus rounds. They also wagered significantly more credits per line when trying to deplete their funds quickly. This experiment shows that experienced slots gamblers have an implicit understanding of reinforcement rate and time on device, and that they are able to manipulate these game outputs at will by adjusting the number of paylines they buy and how many credits they choose to wager. When playing normally, they try to maximize reinforcement rate by purchasing the opportunity to win on many paylines. Player control over reinforcement rate and time on device does not alter payback percentage so there is no monetary advantage to manipulating these game outputs.

Geometric morphometric assessment of sexually dimorphic characteristics of the distal humerus.

A number of recent studies investigated the use of morphological characteristics of the distal humerus to estimate the sex of unknown individuals. Using visual assessment, accuracies ranging from 74% to more than 90% were reported. The aim of this study was to assess these traits with geometric morphometrics, in order to determine if they corroborate the findings described with pure visual assessment. A total sample of 155 female and 175 male humeri of South Africans were used. All humeri were photographed in standardized positions from a posterior and inferior view, and homologous landmarks assigned. Olecranon fossa shape, angle of the medial epicondyle and trochlear symmetry were assessed. Males and females could be separated with accuracies ranging from 78% to 91%. The results of this study confirm the existence of these traits and their usability in assessment of sex from skeletal remains, and the observed anatomical characteristics largely agree with what have been described by visual assessment.

The personality of pathological gamblers: a meta-analysis.

This review summarizes studies of pathological gambling and personality. Meta-analyses were conducted on 44 studies that reported personality traits of pathological gamblers (N = 2134) and nonpathological gambling control groups (N = 5321). Effect size estimates were calculated for 128 comparisons and organized according to the factors associated with two integrative accounts of personality. Four of the meta-analyses examined traits that have previously been found to load on the Urgency, Premeditation, Perseverance, and Sensation Seeking aspects of impulsivity (Whiteside & Lynam 2001). Substantial effects were found for traits associated with Negative Urgency (Cohen's d =.99) and Low Premeditation (d =.84), but not for Low Perseverance or Sensation Seeking. A second set of meta-analyses examined broad domains of personality that have previously been found to load on Negative Affect, Positive Affect, Disagreeable Disinhibition, and Unconscientious Disinhibition (Markon, Krueger, & Watson, 2005). Substantial effects were found for Unconscientious Disinhibition (d =.79), Negative Affect (d =.50), and Disagreeable Disinhibition (d =.50), but not Positive Affect. It was concluded that these individual personality characteristics may be important in the etiology of pathological gambling. The personality profile implicated in the etiology of pathological gambling is similar to that found in a recent meta-analysis of substance use disorders (Kotov, Gamez, Schmidt, & Watson, 2010). These results suggest that pathological gambling may be part of a broad cluster of externalizing psychopathology, and also call into question the current classification of pathological gambling as an Impulse Control Disorder in the DSM-IV.

Weight gain in breast cancer survivors: prevalence, pattern and health consequences.

Weight gain is a common and persistent problem for many breast cancer survivors and is associated with adverse health consequences. A comprehensive review of the English language literature was conducted to investigate the frequency, magnitude and pattern of weight gain among breast cancer survivors, to identify factors that are associated with these changes and to review the clinical significance of weight gain on disease free survival and overall health. While there appears to be a general trend toward a reduction in the magnitude of weight gain in recent years, as many as 50-96% of women experience weight gain during treatment and many, including some women who remain weight stable during treatment, report progressive weight gain in the months and years after diagnosis. Weight gain is more common in women receiving adjuvant chemotherapy, especially for women receiving longer duration treatments and seems to be especially pronounced in premenopausal women. With or without weight gain, unfavourable changes in body composition including fat gain and loss of lean tissue are prevalent. This unique pattern of weight gain and change in body composition is distressing for most women, poses significant risk for the development of co-morbid conditions and may impact on long term disease-free survival.

A cross-sectional analysis of age related changes in the osteometric dimensions of long bones in modern South Africans of European and African descent.

New techniques are continuously developed to establish individualizing characteristics of unknown skeletonized remains. However, the critical evaluations of older, and seemingly standardized, methods are also necessary. Since many of the methods to determine skeletal sex are used in a medico-legal arena, the application of proper techniques to achieve accurate results is paramount. The purpose of this study was to evaluate whether the osteometric variables that are often used in discriminant function formulae to determine sex, namely the dimensions of the proximal and distal articular surfaces and the mid-shaft diameters of the long bones, increase or decrease with the advancement of age. Twenty-three standard anthropometric measurements were taken from the long bones of 404 male (n=106 white, n=298 black) and 189 female (n=82 white, n=107 black) known skeletons housed at the medical schools of the Universities of Pretoria and the Witwatersrand in South Africa. Results indicated that males and females of both ancestral groups were sexually dimorphic for the long bone measurements. The mean size of these measurements demonstrated a statistically significant increase in size from young to old groups in white females and males, with black females remaining static for their measurements and changes with age. Reasons for an increase in size are multi-faceted and may include normal degenerative changes such as bone remodeling, microfractures at articular joint surfaces, and changes in the relationship of cortical and endosteal bone as well as disease (osteoporosis). Males also increase in robusticity long after their epiphyses had closed. These changes may pose challenges to the accurate determination of sex should only metric characteristics be used.

Multiple addictive behaviors in young adults: student norms for the Shorter PROMIS Questionnaire.

The Shorter PROMIS Questionnaire (SPQ; Christo, Jones, Haylett, Stephenson, Lefever & Lefever, 2003) is a multidimensional self report that measures 16 addictive behaviors. This study examined the psychometric properties of the SPQ and collected normative data from 948 students at two Canadian universities. Factor analysis confirmed the existence of two categories of addictive behavior, which Haylett and her colleagues (2004) labelled hedonistic and nurturant. The hedonistic categories included behaviors such as the use of prescription drugs, gambling, caffeine, illegal drugs, alcohol, tobacco and compulsive sex. The nurturant group included behaviors such as compulsive helping, work, relationships, shopping, disordered eating and exercise. Men (N=250) scored higher than women on dominant relationships, exercise, gambling, illegal drugs, alcohol, tobacco and sex. Women (N=698) scored higher on compulsive shopping, food binging and starving. These results suggest that the SPQ may be a useful index of multiple addictive behaviors in college-age people.

Female students' disordered eating and the big five personality facets.

Female undergraduate students at two Canadian universities (N = 378) completed the NEO PI-R (Costa, P.T. & McCrae, R.R. (1992). NEO PI-R Professional Manual. Lutz, FL: Psychological Assessment Resources) and the Eating Attitudes Test (EAT-26; Garner, D. M., Olmstead, M. P., Bohr, Y. & Garfinkel, P. E. (1982). The Eating Attitudes Test: Psychometric features and clinical correlates. Psychological Medicine, 12, 871-878.). Eating disorder symptomatic (N = 43) and nonsymptomatic (N = 335) women differed on facets of Neuroticism, Extraversion, and Agreeableness. Among symptomatic women, the Oral Control subscale of the EAT-26 was correlated significantly with facets of Neuroticism, Agreeableness and Conscientiousness. Specifically, the Impulsivity facet of Neuroticism was positively correlated with the Bulimia and Food Preoccupation subscale of EAT-26, but negatively correlated with the Oral Control and Dieting subscales. Overall, results suggest that high scores on Neuroticism may be a risk factor for development of disordered eating behavior and that the degree of Impulsiveness may predict the eating disorder subtype to which one is most susceptible.

Inhibition in adults with attention deficit/hyperactivity disorder: event-related potentials in the stop task.

The core deficit in Attention Deficit/Hyperactivity Disorder (ADHD) may be a deficiency in executive functions, particularly the processes that are associated with the inhibition of predominant responses. To test this notion in the adult population, healthy undergraduate volunteers and students with ADHD symptoms performed a visual Stop Signal Task (Logan et al. J Exp Psychol: Hum Percept Perform 10:276-291, 1984) while Event-Related brain Potentials were recorded. The two groups did not differ on behavioral measures of performance, but there was a significant difference in the N2-P3 component. These results underline the robustness of an N2-P3 difference between healthy adults and people with ADHD symptoms that have persisted into young adulthood.

Symptoms of exercise dependence and physical activity in students.

Health professionals recognize the benefits of moderate physical activity and encourage clients to engage in some form of activity on a regular basis. In spite of these recognized benefits, there are growing concerns that some may exercise at levels detrimental to health. The term exercise dependence refers to those individuals whose extreme exercise schedules interfere with their social, occupational, and family lives. The purpose of this study was to examine the relationship between weekly exercise habits and scores on the Exercise Dependence Questionnaire in a sample of undergraduate students (213 women and 79 men). Overall, participants who reported high activity scored higher than those reporting low activity on subscales measuring interference with family and social life, positive reward, withdrawal, exercise for social reasons, exercise for health reasons, and stereotyped behavior.

RNA silencing in plants--defense and counterdefense.

RNA silencing is a remarkable type of gene regulation based on sequence-specific targeting and degradation of RNA. The term encompasses related pathways found in a broad range of eukaryotic organisms, including fungi, plants, and animals. In plants, it serves as an antiviral defense, and many plant viruses encode suppressors of silencing. The emerging view is that RNA silencing is part of a sophisticated network of interconnected pathways for cellular defense, RNA surveillance, and development and that it may become a powerful tool to manipulate gene expression experimentally.

RNA-based silencing strategies in plants.

In plants, double-stranded RNA can silence genes by triggering degradation of homologous RNA in the cytoplasm and by directing methylation of homologous nuclear DNA sequences. Analyses of Arabidopsis mutants and plant viral suppressors of silencing are unraveling RNA-silencing mechanisms, which require common proteins in diverse organisms, and are assessing the role of methylation in transcriptional and posttranscriptional gene silencing.

HC-Pro suppression of transgene silencing eliminates the small RNAs but not transgene methylation or the mobile signal.

Post-transcriptional gene silencing (PTGS) is a sequence-specific RNA degradation mechanism that is widespread in eukaryotic organisms. It is often associated with methylation of the transcribed region of the silenced gene and with accumulation of small RNAs (21 to 25 nucleotides) homologous to the silenced gene. In plants, PTGS can be triggered locally and then spread throughout the organism via a mobile signal that can cross a graft junction. Previously, we showed that the helper component-proteinase (HC-Pro) of plant potyviruses suppresses PTGS. Here, we report that plants in which PTGS has been suppressed by HC-Pro fail to accumulate the small RNAs associated with silencing. However, the transgene locus of these plants remains methylated. Grafting experiments indicate that HC-Pro prevents the plant from responding to the mobile silencing signal but does not eliminate its ability to produce or send the signal. These results demonstrate that HC-Pro functions downstream of transgene methylation and the mobile signal at a step preceding accumulation of the small RNAs.

A calmodulin-related protein that suppresses posttranscriptional gene silencing in plants.

Posttranscriptional gene silencing (PTGS) is an ancient eukaryotic regulatory mechanism in which a particular RNA sequence is targeted and destroyed. The helper component-proteinase (HC-Pro) of plant potyviruses suppresses PTGS in plants. Using a yeast two-hybrid system, we identified a calmodulin-related protein (termed rgs-CaM) that interacts with HC-Pro. Here we report that rgs-CaM, like HC-Pro itself, suppresses gene silencing. Our work is the first report identifying a cellular suppressor of PTGS.

RNA viruses as inducers, suppressors and targets of post-transcriptional gene silencing.

Post-transcriptional gene silencing (PTGS) is a fundamental regulatory mechanism operating in diverse types of organisms, but the cellular components of the gene silencing machinery and the regulation of the process are not understood. Recent findings that cytoplasmically replicating RNA viruses act as both targets and inducers of PTGS has led to the idea that PTGS may have evolved as an anti-viral defense mechanism in plants. Consistent with this hypothesis, it has been found that certain plant viruses encode proteins that suppress PTGS. From a practical standpoint, an understanding of the mechanisms by which viruses regulate PTGS may well lead to better ways to control gene expression in plants. It is often desirable to overexpress selected beneficial genes or to silence detrimental ones in order to confer a particular phenotype. Induction of PTGS using RNA viruses as vectors or as transgenes provides a reliable and efficient way to interfere with the expression of a specific gene or with a family of genes. Conversely, expression of viral suppressors has significant potential to improve yields in technologies that use plants to express beneficial gene products. Given the antiviral nature of gene silencing in plants and the indications that PTGS is an ancient mechanism in eukaryotic organisms, understanding the phenomenon in plants could well lead to the development of anti-viral strategies in both plants and animals.

Plant viral suppressors of post-transcriptional silencing do not suppress transcriptional silencing.

Homology-dependent gene silencing is a regulatory mechanism that limits RNA accumulation from affected loci either by suppression of transcription (transcriptional gene silencing, TGS) or by activation of a sequence-specific RNA degradation process (post-transcriptional gene silencing, PTGS). The P1/HC-Pro sequence of plant potyviruses and the 2b gene of the cucumber mosaic virus have been shown to interfere with PTGS. The ability of these viral suppressors of PTGS to interfere with TGS was tested using the 271 locus which imposes TGS on transgenes under 35S or 19S promoters and PTGS on the endogenous nitrite reductase gene (Nii). Both P1/HC-Pro and 2b reversed PTGS of Nii genes in 271-containing tobacco plants, but failed to reverse TGS of 35S-GUS transgenes in the same plant. P1/HC-Pro expression from a transgene also failed to suppress either the initiation or maintenance of TGS imposed by the NOSpro-silencing locus, H2. These results indicate that PTGS and TGS operate through unlinked pathways or that P1/HC-Pro and 2b interfere at step(s) in PTGS that are downstream of any common components in the two pathways. The data suggest a simple assay to identify post-transcriptionally silenced transgenic lines with the potential to be stably converted to high expressing lines.

A viral suppressor of gene silencing in plants.

Gene silencing is an important but little understood regulatory mechanism in plants. Here we report that a viral sequence, initially identified as a mediator of synergistic viral disease, acts to suppress the establishment of both transgene-induced and virus-induced posttranscriptional gene silencing. The viral suppressor of silencing comprises the 5'-proximal region of the tobacco etch potyviral genomic RNA encoding P1, helper component-proteinase (HC-Pro) and a small part of P3, and is termed the P1/HC-Pro sequence. A reversal of silencing assay was used to assess the effect of the P1/HC-Pro sequence on transgenic tobacco plants (line T4) that are posttranscriptionally silenced for the uidA reporter gene. Silencing was lifted in offspring of T4 crosses with four independent transgenic lines expressing P1/HC-Pro, but not in offspring of control crosses. Viral vectors were used to assess the effect of P1/HC-Pro expression on virus-induced gene silencing (VIGS). The ability of a potato virus X vector expressing green fluorescent protein to induce silencing of a green fluorescent protein transgene was eliminated or greatly reduced when P1/HC-Pro was expressed from the same vector or from coinfecting potato virus X vectors. Expression of the HC-Pro coding sequence alone was sufficient to suppress virus-induced gene silencing, and the HC-Pro protein product was required for the suppression. This discovery points to the role of gene silencing as a natural antiviral defense system in plants and offers different approaches to elucidate the molecular basis of gene silencing.

Plant viral synergism: the potyviral genome encodes a broad-range pathogenicity enhancer that transactivates replication of heterologous viruses.

Synergistic viral diseases of higher plants are caused by the interaction of two independent viruses in the same host and are characterized by dramatic increases in symptoms and in accumulation of one of the coinfecting viruses. In potato virus X (PVX)/potyviral synergism, increased pathogenicity and accumulation of PVX are mediated by the expression of potyviral 5' proximal sequences encoding P1, the helper component proteinase (HC-Pro), and a fraction of P3. Here, we report that the same potyviral sequence (termed P1/HC-Pro) enhances the pathogenicity and accumulation of two other heterologous viruses: cucumber mosaic virus and tobacco mosaic virus. In the case of PVX-potyviral synergism, we show that the expression of the HC-Pro gene product, but not the RNA sequence itself, is sufficient to induce the increase in PVX pathogenicity and that both P1 and P3 coding sequences are dispensable for this aspect of the synergistic interaction. In protoplasts, expression of the potyviral P1/HC-Pro region prolongs the accumulation of PVX (-) strand RNA and transactivates expression of a reporter gene from a PVX subgenomic promoter. Unlike the synergistic enhancement of PVX pathogenicity, which requires only expression of HC-Pro, the enhancement of PVX (-) strand RNA accumulation in protoplasts is significantly greater when the entire P1/HC-Pro sequence is expressed. These results indicate that the potyviral P1/HC-Pro region affects a step in disease development that is common to a broad range of virus infections and suggest a mechanism involving transactivation of viral replication.