Cannabis Use for Medicinal Purposes among Canadian University Students.

OBJECTIVE: The study sought to describe a Canadian sample of university students' medicinal use of cannabis, including prevalence of cannabis use disorder (CUD) and replacement of traditional treatments with cannabis. METHOD: A random sample of 4000 university students was asked to complete a cross-sectional web-based survey. The survey was completed by 2212 (average age 23.2 years, SD = 5.2 years), representing a 55.3% response rate. To be eligible, students had to be enrolled in a class on campus and were 18 years or older. RESULT: Half (52%) of respondents used cannabis at least once in their lifetime, with ∼11% reporting medicinal cannabis use. Recreational motives to use cannabis were common among medicinal users (85%), several (38%) replaced traditional medication with cannabis, and more than a third received authorization by a health care provider. Of the medicinal users, 13.6% met the criteria for CUD. Common ailments for medicinal cannabis use were anxiety, sleep problems, depression, and pain. When mental health-related categories are combined, 78.2% of medicinal users used for at least 1 mental health condition. CONCLUSIONS: Medicinal cannabis use occurs among university students. None of the ailments listed by medicinal users meet the Canadian Family Physicians prescribing guidelines, and most are not among those viewed by the National Academies of Science, Engineering, and Medicine as having strong evidence for therapeutic value. The results raise concerns for health care providers who are authorizing or counselling patients' considering medicinal cannabis.

Proton spectroscopy study of the dorsolateral prefrontal cortex in youth with familial depression.

AIM: Structural, functional, and metabolic changes in the dorsolateral prefrontal cortex (DLPFC) are implicated in the pathogenesis of major depressive disorder (MDD). We used proton magnetic resonance spectroscopy ((1) H-MRS) to examine the metabolite choline (glycerophosphocholine plus phosphocholine), which is used as an index of membrane integrity in the left DLPFC, in adolescents and young adults with MDD who were treatment-resistant and had a positive family history compared to healthy controls. Differences in the choline resonance indicate an imbalance between synthesis and degradation activity of neuronal and glia membrane phospholipids. METHODS: Seventeen adolescents with MDD and 11 healthy controls underwent (1) H-MRS. A short echo point-resolved spectroscopy (echo time = 30 ms, repetition time = 2000 ms) protocol was used with a voxel (4.5cm(3) , 128 averages) placed within the left DLPFC. RESULTS: There were significantly increased choline (P = 0.04) and creatine concentrations (P = 0.005) in the left DLPFC of the MDD group compared to controls. In MDD participants, choline concentration correlated with scores on the Beck Depression Inventory (r = 0.41, P = 0.03). CONCLUSION: Increased left DLPFC choline and creatine levels in depressed adolescents may be biomarkers for the disorder. The increased choline levels may indicate abnormalities in neuronal membrane integrity, and the increased creatine could be reflective of altered energy demands and metabolism.

Glass eel migration in an urbanized catchment: an integral bottleneck assessment using mark-recapture.

Diadromous fish such as the European eel (Anguilla anguilla L.) are hampered by a high density of barriers in estuaries and freshwater systems. Modified and fragmented waterbodies lack tidal flows, and habitat may be less accessible and underutilized compared to free-flowing rivers and estuaries. With rising sea levels and increased occurrence of droughts, the number of barriers may further increase, implying that the need to study migration in such areas may even become more urgent worldwide. To study glass eel migration and behaviour in such highly modified water systems, a mark-recapture study was carried out in the North Sea Canal (NSC) basin, which drains into the North Sea via a large sluice complex. In total, eight uniquely tagged groups (3,797 glass eels) were released near the sluice complex, and 11 groups (2,663 glass eels) were released at inland barriers upstream over a 28 km long stretch in the NSC in spring 2018. The sluice complex attracted 10.3 million glass eel and did not block or delay their immigration. The large and diurnally intensively used coastal ship locks and allowings some saltwater intrusion, efficiently facilitated glass eel migration. Once in the NSC, water outlets from adjacent polders attracted glass eels relative proportional to the discharge of pumping stations. In the NSC, average migration speeds of 0.7 km/day (max. 1.8 km/day) were measured, and this increased with higher temperatures. Redistribution of glass eel from accumulations at inland barriers to other outlet locations was observed in both upstream and downstream directions in the NSC. Passage success and residence time ('delays' of 4.1-13.7 days) varied between the different inland barriers. Most of the glass eel, however, appears to settle in the easily accessible habitats within the brackish NSC catchment. This study combined an integral assessment of successive bottlenecks in a modified inland water system.

The draft genome sequence of Arsenophonus nasoniae, son-killer bacterium of Nasonia vitripennis, reveals genes associated with virulence and symbiosis.

Four percent of female Nasonia vitripennis carry the son-killer bacterium Arsenophonus nasoniae, a microbe with notably different biology from other inherited parasites and symbionts. In this paper, we examine a draft genome sequence of the bacterium for open reading frames (ORFs), structures and pathways involved in interactions with its insect host. The genome data suggest that A. nasoniae carries multiple type III secretion systems, and an array of toxin and virulence genes found in Photorhabdus, Yersinia and other gammaproteobacteria. Of particular note are ORFs similar to those known to affect host innate immune functioning in other bacteria, and four ORFs related to pro-apoptotic exotoxins. The genome sequences for both A. nasoniae and its Nasonia host are useful tools for examining functional genomic interactions of microbial survival in hostile immune environments, and mechanisms of passage through gut epithelia, in a whole organism context.

Characteristics of the genome of Arsenophonus nasoniae, son-killer bacterium of the wasp Nasonia.

We report the properties of a draft genome sequence of the bacterium Arsenophonus nasoniae, son-killer bacterium of Nasonia vitripennis. The genome sequence data from this study are the first for a male-killing bacterium, and represent a microorganism that is unusual compared with other sequenced symbionts, in having routine vertical and horizontal transmission, two alternating hosts, and being culturable on cell-free media. The resulting sequence totals c. 3.5 Mbp and is annotated to contain 3332 predicted open reading frames (ORFs). Therefore, Arsenophonus represents a relatively large genome for an insect symbiont. The annotated ORF set suggests that the microbe is capable of a broad array of metabolic functions, well beyond those found for reproductive parasite genomes sequenced to date and more akin to horizontally transmitted and secondary symbionts. We also find evidence of genetic transfer from Wolbachia symbionts, and phage exchange with other gammaproteobacterial symbionts. These findings reflect the complex biology of a bacterium that is able to live, invade and survive multiple host environments while resisting immune responses.

Combined ground and aerial measurements resolve vent-specific gas fluxes from a multi-vent volcano.

Volcanoes with multiple summit vents present a methodological challenge for determining vent-specific gas emissions. Here, using a novel approach combining multiple ultraviolet cameras with synchronous aerial measurements, we calculate vent-specific gas compositions and fluxes for Stromboli volcano. Emissions from vent areas are spatially heterogeneous in composition and emission rate, with the central vent area dominating passive emissions, despite exhibiting the least explosive behaviour. Vents exhibiting Strombolian explosions emit low to negligible passive fluxes and are CO2-dominated, even during passive degassing. We propose a model for the conduit system based on contrasting rheological properties between vent areas. Our methodology has advantages for resolving contrasting outgassing dynamics given that measured bulk plume compositions are often intermediate between those of the distinct vent areas. We therefore emphasise the need for a vent-specific approach at multi-vent volcanoes and suggest that our approach could provide a transformative advance in volcano monitoring applications.

Author Correction: Combined ground and aerial measurements resolve vent-specific gas fluxes from a multi-vent volcanic system.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Repetitive Transcranial Magnetic Stimulation in Youth With Treatment Resistant Major Depression.

Background: Major depressive disorder (MDD) is common in youth and treatment options are limited. We evaluated the effectiveness and safety of repetitive transcranial magnetic stimulation (rTMS) in adolescents and transitional aged youth with treatment resistant MDD. Methods: Thirty-two outpatients with moderate to severe, treatment-resistant MDD, aged 13-21 years underwent a three-week, open-label, single center trial of rTMS (ClinicalTrials.gov identifier NCT01731678). rTMS was applied to the left dorsolateral prefrontal cortex (DLPFC) using neuronavigation and administered for 15 consecutive week days (120% rest motor threshold; 40 pulses over 4 s [10 Hz]; inter-train interval, 26 s; 75 trains; 3,000 pulses). The primary outcome measure was change in the Hamilton Depression Rating Scale (Ham-D). Treatment response was defined as a >50% reduction in Ham-D scores. Safety and tolerability were also examined. Results: rTMS was effective in reducing MDD symptom severity (t = 8.94, df = 31, p < 0.00001). We observed 18 (56%) responders (≥ 50% reduction in Ham-D score) and 14 non-responders to rTMS. Fourteen subjects (44%) achieved remission (Ham-D score ≤ 7 post-rTMS). There were no serious adverse events (i.e., seizures). Mild to moderate, self-limiting headaches (19%) and mild neck pain (16%) were reported. Participants ranked rTMS as highly tolerable. The retention rate was 91% and compliance rate (completing all study events) was 99%. Conclusions: Our single center, open trial suggests that rTMS is a safe and effective treatment for youth with treatment resistant MDD. Larger randomized controlled trials are needed. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01731678.

History of suicide attempt and right superior temporal gyrus volume in youth with treatment-resistant major depressive disorder.

BACKGROUND: Growing evidence suggests an endophenotype for suicidality, including brain morphometric features, could provide an improved platform for suicide risk assessment. Reduced right superior temporal gyrus (rSTG) volumes have been implicated in suicidality across psychiatric disorders. Treatment-resistant depression (TRD) has unique neurobiology and adolescents with TRD are at increased suicide risk. Here, we investigated whether reduced rSTG volume was present in adolescents with TRD and history of suicide attempt. METHODS: 45 adolescents - 14 with history of suicide attempt and TRD, 14 without a suicide attempt history and TRD, and 17 healthy controls - underwent magnetic resonance imaging and reconstructed rSTG volumes were compared. Depressive and anxious symptoms were assessed with Hamilton depression and anxiety rating scales, and differences between attempters and non-attempters were explored. RESULTS: Adolescents with TRD and history of suicide attempt showed reduced rSTG volume compared to healthy controls. Exploratory analyses revealed greater diurnal variation in depressive symptoms in the suicide attempt group compared to non-attempters. LIMITATIONS: Sample size and temporal separation between suicide attempt date and data collection limits interpretation of findings. CONCLUSIONS: Reduced rSTG volume may serve as a marker of suicide attempt in adolescence and specific symptom features may have a role in suicide risk assessment. Presently, risk assessment is limited by patient self-report and clinical judgement. A biological model of suicidality will be key to improve risk assessment and could lead to novel treatment approaches. Our findings extend previous results and contribute to our neurobiological understanding of suicidality.

A pilot study of hippocampal N-acetyl-aspartate in youth with treatment resistant major depression.

BACKGROUND: Smaller hippocampal volumes, as assessed by magnetic resonance imaging (MRI), and proton magnetic resonance spectroscopy (1H-MRS) indexed alterations in brain metabolites have been identified in adults with major depressive disorder (MDD). Our group has found similar effects in MDD youth. However, this has not been studied in youth with treatment resistant MDD (TRD), nor has the interaction between regional N-acetyl-aspartate and volume deficits. N-acetyl-aspartate is an amino acid in the synthesis pathway of glutamate, and serves a marker of neuronal viability/number. METHODS: Fifteen typically developing youth (16-22 years of age; 7 males, 8 females) and eighteen youth with TRD (14-22 years of age; 8 males, 10 females) underwent 1H-MRS and MRI on a 3T scanner. A short echo PRESS protocol was used with voxels in the right and left hippocampi (6mL each). Hippocampal volume was evaluated using FreeSurfer. RESULTS: Compared with the typically developing group, youth with TRD had lower concentrations of N-acetyl-aspartate in the left hippocampus (p=0.004), and a trend for smaller left hippocampal volume (p=0.067). In TRD subjects, hippocampal N-acetyl-aspartate was inversely correlated with left (r=-0.68, p=0.003) but not right hippocampal volume. Right hippocampal glutamate+glutamine was greater in TRD youth compared to typically developing controls (p=0.007). CONCLUSIONS: These results suggest a neurochemical and structural deficit in the hippocampi of youth with TRD. These findings fit with the role of N-acetyl-aspartate in glutamate neurotransmission and the effect of glutamate on brain morphology.

Insecticide-treated bed-nets for malaria mosquito control.

Pyrethroid-treated bed-nets act against late-night biting mosquitoes, like traps baited by the body odor of the occupant. The personal protective effect of treated nets is considerable, even if they are torn. However, some biting of the occupants does occur, as shown by matching microsatellite alleles in mosquito blood meals to those of net occupants. When whole communities were provided with treated nets, ovarian age grading showed that mosquito survival was reduced, and so was the number of sporozoite-positive mosquitoes in malarious communities. Thus, a high percentage of coverage of all members of malaria-endemic communities is considered to be the most effective way of providing protection for highly malaria-vulnerable children and pregnant women. Teams distributing nets or retreating them free of charge show high productivity, and we consider this the most cost-effective way to proceed. There is evidence for reduced anti-malaria antibody levels in children in communities where treated nets have long been used. However, overall benefits in reduced anemia and mortality are sustained. A high frequency of the kdr resistance gene has not prevented pyrethroid-treated nets from functioning, but it is important to develop alternative fabric treatments in case stronger forms of resistance emerge.

Childhood adversity and subsequent mental health status in adulthood: screening for associations using two linked surveys.

AIMS: Accumulating evidence links childhood adversity to negative health outcomes in adulthood. However, most of the available evidence is retrospective and subject to recall bias. Published reports have sometimes focused on specific childhood exposures (e.g. abuse) and/or specific outcomes (e.g. major depression). Other studies have linked childhood adversity to a large and diverse number of adult risk factors and health outcomes such as cardiovascular disease. To advance this literature, we undertook a broad examination of data from two linked surveys. The goal was to avoid retrospective distortion and to provide a descriptive overview of patterns of association. METHODS: A baseline interview for the Canadian National Longitudinal Study of Children and Youth collected information about childhood adversities affecting children aged 0-11 in 1994. The sampling procedures employed in a subsequent study called the National Population Health Survey (NPHS) made it possible to link n = 1977 of these respondents to follow-up data collected later when respondents were between the ages of 14 and 27. Outcomes included major depressive episodes (MDE), some risk factors and educational attainment. Cross-tabulations were used to examine these associations and adjusted estimates were made using the regression models. As the NPHS was a longitudinal study with multiple interviews, for most analyses generalized estimating equations (GEE) were used. As there were multiple exposures and outcomes, a statistical procedure to control the false discovery rate (Benjamini-Hochberg) was employed. RESULTS: Childhood adversities were consistently associated with a cluster of potentially related outcomes: MDE, psychotropic medication use and smoking. These outcomes may be related to one another since psychotropic medications are used in the treatment of major depression, and smoking is strongly associated with major depression. However, no consistent associations were observed for other outcomes examined: physical inactivity, excessive alcohol consumption, binge drinking or educational attainment. CONCLUSIONS: The conditions found to be the most strongly associated with childhood adversities were a cluster of outcomes that potentially share pathophysiological connections. Although prior literature has suggested that a very large number of adult outcomes, including physical inactivity and alcohol-related outcomes follow childhood adversity, this analysis suggests a degree of specificity with outcomes potentially related to depression. Some of the other reported adverse outcomes (e.g. those related to alcohol use, physical inactivity or more distal outcomes such as obesity and cardiovascular disease) may emerge later in life and in some cases may be secondary to depression, psychotropic medication use and smoking.

Retrospective and prospectively assessed childhood adversity in association with major depression, alcohol consumption and painful conditions.

BACKGROUND: Considerable evidence now links childhood adversity to a variety of adult health problems. Unfortunately, almost all of these studies have relied upon retrospective assessment of childhood events, creating a vulnerability to bias. In this study, we sought to examine three associations using data sources that allowed for both prospective and retrospective assessment of childhood events. METHODS: A 1994 national survey of children between the ages of 0 and 11 collected data from a 'person most knowledgeable' (usually the mother) about a child. It was possible to link data for n = 1977 of these respondents to data collected from the same people in a subsequent adult study. The latter survey included retrospective reports of childhood adversity. We examined three adult health outcomes in relation to prospectively and retrospectively assessed childhood adversity: major depressive episodes, excessive alcohol consumption and painful conditions. RESULTS: A strong association between childhood adversities (as assessed by both retrospective and prospective methods) and major depression was identified although the association with retrospective assessment was stronger. Weaker associations were found for painful conditions, but these did not depend on the method of assessment. Associations were not found for excessive alcohol consumption irrespective of the method of assessment. CONCLUSIONS: These findings help to allay concerns that associations between childhood adversities and health outcomes during adulthood are merely artefacts of recall bias. In this study, retrospective and prospective assessment strategies produced similar results.

Synthesis of novel thiol-containing citric acid analogues. Kinetic evaluation of these and other potential active-site-directed and mechanism-based inhibitors of ATP citrate lyase.

ATP citrate lyase is an enzyme involved in mammalian lipogenesis and cholesterogenesis. Inhibitors of the enzyme represent a potentially novel class of hypolipidemic agents. Citric acid analogues 5-16 bearing electrophilic and latent electrophilic substituents were synthesized and evaluated as irreversible inhibitors of the enzyme. The design of these agents was based on the classical enzymatic mechanism where an active-site nucleophile (thiol) was believed to be critically involved in catalysis. Reversible inhibition (Ki's ranging from ca. 20 to 500 microM) was observed for compounds 5, 10, and 12-16. Compounds 6-9 and 11 had no appreciable affinity for enzyme (Ki > 1 mM). Time-dependent inactivation of the enzyme by 5-16 was not detected following long incubation times (> 1 h, 37 degrees C) at 2 mM inhibitor concentrations.

Nonincisional correction of epiblepharon and congenital entropion.

Nonincisional suture techniques are used for the treatment of epiblepharon and congenital entropion. An explanation for the unstable eyelid seems to involve similar developmental anomalies of the eyelid retractor. Congenital entropion has been treated promptly in the past. Contrary to tradition, symptomatic epiblepharon should also be treated early.

Malignant melanoma of the orbit in a black patient with ocular melanocytosis.

Ocular melanocytosis has been associated with an increased incidence of choroidal melanomas in white patients. Recently reported was a case of a choroidal melanoma in a black patient with oculodermal melanocytosis. We treated a case of an orbital malignant melanoma arising in a black patient with ocular melanocytosis.

Treatment of Aspergillus fumigatus keratitis in rabbits with oral and topical ketoconazole.

Aspergillus fumigatus keratitis was established in rabbits by intrastromal injection of a suspension containing 5,000 spores. After a 48-hour incubation period, the animals were treated with oral and topical ketoconazole alone and in combination with topical natamycin for five days. Colony counts per cornea were obtained at the conclusion of the treatment period. Based on these colony counts, neither oral nor topical ketoconazole was effective despite moderate in vitro sensitivity of the fungus to ketoconazole. Oral and topical ketoconazole used in conjunction with natamycin, however, appeared to augment sterilization of A. fumigatus in this model of fungal keratitis.

Preliminary field observations on the flight speed of a phlebotomine sandfly.

From observations with a portable wind tunnel used in the field in southern France, it is estimated that the maximum flight speed of Phlebotomus ariasi is in the range 0.65-0.70 m/sec (2.3 to 2.5 km/h).

Mortality of under-fives in a rural area of holoendemic malaria transmission.

From January 1992 to December 1993, a total of 361 births and 243 deaths were recorded by village reporters in five villages in Muheza District, north eastern Tanzania. Among those aged less than one year 48 deaths were recorded, giving an infant mortality rate of 133 per 1000 live births (95% CI 97.9-168.0). There were 42 deaths among the censused population of 845 children aged 1-4 years (24.8/1000/year, 95% CI: 17.4-32.3). Verbal autopsy questionnaires were administered to parents or close relatives of 83 of the dead infants and children. From analysis of these, 30 of the deaths were tentatively attributed to malaria. The results are discussed in relation to other studies in East and West Africa and to the prospects for reducing mortality by use of insecticide impregnated bednets.

PIP: The rural areas of Muheza District in northeastern Tanzania are holoendemic for malaria. In Tanzania, malaria is the largest single cause of hospital attendance, the second largest cause for hospital admission, and one of the leading causes of hospital deaths. Hospital data, however, only reveal part of the picture of childhood mortality because most such deaths in rural areas occur at home. The authors investigated the causes of infant and child mortality in five villages near Muheza to collect baseline data in preparation for aa large-scale study planned to explore the impact of impregnated bednets upon infant and child mortality. Records of births, deaths, ages at death, and supposed causes of death were collected by village reporters, while verbal autopsies were obtained from parents or close relatives of dead infants and children. The study 361 births and 243 deaths were recorded by the village reporters from January 1992 to December 1993. There were 48 deaths to infants under one year old for an infant mortality rate of 133/1000 live births. 42 deaths were recorded among the censused population of 845 children aged 1-4 years. Verbal autopsy questionnaires were administered to parents or close relatives of 83 of the dead infants and children. On analysis, 30 deaths were tentatively attributed to malaria. These results are discussed in relation to other studies in East and West Africa, and to the prospects for reducing mortality through the use of insecticide-impregnated bednets.

Trial of pyrethroid impregnated bednets in an area of Tanzania holoendemic for malaria. Part 1. Operational methods and acceptability.

In five Tanzanian villages, nets impregnated with permethrin or lambdacyhalothrin were given out. The people received them enthusiastically and brought their nets for re-impregnation at six monthly intervals. Bioassays showed that the insecticidal power of permethrin impregnated nets remained adequate for six months unless the nets were washed. Nets with 30 mg lambdacyhalothrin/m2 retained high insecticidal power despite washing, but this dose caused temporary cold-like symptoms in those sleeping under freshly treated dry nets. Methods by which durable bednets might be made affordable by Tanzanian villagers are discussed.