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At least 19 recordsLinked to original sources
PubMed2026

Multi-Ancestry Survival GWAS of Substance Use Initiation in the ABCD Study.

BACKGROUND: Substance use initiation in adolescence is influenced by both genetic and environmental factors; however, large-scale genetic studies often treat initiation as a binary outcome and underuse longitudinal timing information. METHODS: We conducted time-to-event (survival) genome-wide association analyses (GWAS) of initiation for four outcomes-alcohol, nicotine, cannabis, and any substance use-using longitudinal follow-up data from the Adolescent Brain Cognitive Development (ABCD) Study. We performed ancestry-stratified GWAS within European (EUR), African (AFR), and Hispanic (HISP) groups, applying consistent quality control and covariate adjustment. Summary statistics were harmonized across ancestries and meta-analyzed using inverse-variance weighted fixed-effects and DerSimonian-Laird random-effects models. We evaluated genomic inflation and heterogeneity (Cochran's Q and I 2), identified independent lead variants at genome-wide and suggestive significance thresholds, and assessed cross-trait overlap of associated loci. RESULTS: In the multi-ancestry meta-analysis, we observed suggestive association signals across traits (minimum p-values: alcohol ~ 1 &#xd7; 10-7, any ~ 1 &#xd7; 10-7, cannabis ~ 5 &#xd7; 10-8, nicotine ~ 1 &#xd7; 10-8). Nicotine initiation showed one genome-wide significant variant in both fixed- and random-effects meta-analyses (p < 5 &#xd7; 10-8). Across traits, suggestive loci demonstrated limited overlap, with the strongest concordance between alcohol and any substance use, consistent with shared liability. Heterogeneity statistics indicated that some loci exhibited cross-ancestry variation in effect estimates. CONCLUSIONS: Survival GWAS leveraging initiation timing can identify genetic signals that may be missed by binary designs and enables principled multi-ancestry synthesis. Our results highlight both shared and trait-specific genetic contributions to early substance initiation and provide a foundation for downstream functional annotation and integrative modeling with environmental risk factors. These findings demonstrate the value of incorporating developmental timing into genetic discovery and provide a framework for integrating longitudinal risk modeling with genomic analyses.

ABCD↗
PubMed1992

Race differences in antisocial behaviors and attitudes and early initiation of substance use.

This article examines racial differences in self-reported delinquency, school trouble, antisocial attitudes, and toughness and in teacher-rated aggressive and inattentive behaviors among fifth grade black, white, and Asian American subjects. Also examined are the relationships of these variables to substance initiation within each racial group. Controlling for socio-economic status, racial groups differed from one another in self-reported delinquency, school trouble and toughness, and in teacher-rated aggressiveness and inattention. Antisocial behavior and attitudes were stronger predictors of substance initiation for Asian American than for black and white children. For white children both self-reported and teacher-rated behavior were significantly related to substance initiation. For black children, only self-reported antisocial behavior, and for Asian American children only self-reported delinquent behavior and attitudes predicted substance initiation. Implications for prevention and research are discussed.

Adolescent↗
PubMed1992

Ethnic differences in family factors related to early drug initiation.

The literature on family predictors of substance use for the general population is reviewed and compared to findings for three specific ethnic groups: black, white and Asian Americans. Rates of substance use initiation are examined in a sample of 919 urban 5th-grade students. Ethnic differences on measures of family predictors are examined and significant ethnic differences are found on several of these factors. Finally, separate regressions for black, white and Asian American youths of family factors on the variety of substances initiated examine ethnic similarities and differences in predictors. The results demonstrate significant differences by ethnicity in family management practices, involvement in family activity, sibling deviance, parental disapproval of children's drinking and family structure. The regression equations identified unique as well as common predictors of the variety of substances initiated by the end of 5th grade. Implications of the results are discussed.

Alcoholism↗
PubMed2026

Co-Use of Some Substances Associated With Higher Doses in Adolescents: Findings From the Adolescent Brain Cognitive Development Study.

PURPOSE: Adolescence is a critical developmental period marked by heightened vulnerability to initiating substance use, with long-term implications for health and behavior. Nicotine, alcohol, and cannabis are the most commonly used substances among adolescents. Their use often co-occurs but few studies have described or quantified the patterns and doses of substance co-use in this vulnerable population. METHODS: We used data from six waves of the Adolescent Brain Cognitive Development study. Substance use was measured through a web-based timeline followback interview, and outcomes are operationalized into substance use quantity (in standard units), single use, and co-use (use of two substances on the same day) of alcohol, cannabis, and nicotine. Group differences of average dose in standard units between single use and co-use for each substance class were analyzed using linear mixed-effects modeling in years 4-6. RESULTS: The average dose of nicotine was significantly higher when co-used with alcohol (4.32; 95% confidence interval [CI]: 2.55-6.09; p < .001) or when co-used with cannabis (4.41; 95% CI: 2.76-6.05; p < .001) in year 6; nicotine trends were similar in years four and five. In year 6, the average dose of alcohol was higher when co-used with cannabis (1.87; 95% CI: 0.37-3.36; p = .004) or co-used with nicotine (1.64; 95% CI: 0.06-3.22; p = .03) compared to single use of alcohol. The average dose of cannabis was not significantly different when used singularly or co-used with either alcohol or nicotine in our study years. DISCUSSION: During adolescence, the co-use of substances (namely alcohol and nicotine) may lead to higher average doses compared to single-substance use.

Humans↗
PubMedDate not supplied

Photometric extraction method for determination of cefalotin.

A selective, accurate and precise photometric method for the determination of cefalotin (1) is proposed. The method is based on a preliminary hydrolysis of the antibiotic in a strong sulphuric acid medium at 100 degrees C for 15 min. The 2-thienylacetic acid (2) formed as degradation product is determined photometrically with ninhydrin in strongly acidic solution. In these conditions 2 forms a yellow reaction product, which is extracted with chloroform and the absorbance measured at 423 nm. The reaction is practically specific as none of the initial substances used in the preparation of cefalotin or of its degradation products (except 2) reacts with ninhydrin under these conditions. The only other antibiotic which also gives a coloured product with ninhydrin in this strongly acidic medium is cefalexin. The latter however does not interfere at its coloured product absorbs at 520 nm. The method is simple, fast and with sufficient accuracy and precision (coefficient of variation 0,57--0,88% and relative error 0,41--0,64%).

Cephalothin↗
PubMedDate not supplied

Prediction of intravenous drug use.

Information about lifetime intravenous drug use (IVDU) was obtained from 1,062 relatives of hospitalized alcoholics, felons, and control subjects, of whom 92 had a history of IVDU and an additional 230 had a history of substantial, but non-IV drug use. The IVDUs were significantly more likely than all other subjects to have reported experiencing numerous behavioral and social difficulties relating to conduct difficulties, early initiation of substance use, and disrupted living situation before the age of 15. They were also more likely to have exhibited conduct problems than other drug users. In multivariate analyses, four symptoms (fighting in school, juvenile arrest, initiation of cannabis use before 15, or initiation of sexual activity before 15) differentiated IVDUs. A history of greater numbers of these problems was associated with increasing risk for IVDU, both when compared with the total sample and when compared with other drug users.

Adolescent↗
PubMed1992

Adolescents' multisubstance use patterns: the role of heavy alcohol and cigarette use.

OBJECTIVES: Knowledge about the roles that heavy alcohol and cigarette use play in patterns of concurrent substance use among adolescents is lacking despite studies showing that adolescent substance users are typically multisubstance users and that alcohol and cigarettes are commonly used heavily by those who use illicit substances. METHODS: The roles of increasing use and heavy first-time use of alcohol and cigarettes in multisubstance use patterns were examined in a cohort of 4192 secondary students who were surveyed three times over a 4-year period. RESULTS: When subsequent use patterns were compared for students who increased their levels of alcohol or cigarette use and those who initiated use for the first time but at heavy frequencies, analyses indicated that the former group was more likely to initiate the subsequent use of other substances and to maintain and increase use already initiated. CONCLUSIONS: These results suggest that adolescents are likely to have been involved in a history of licit substance use characterized by increasing levels of use before progressing to and maintaining the use of other substances. Increasing frequencies of alcohol and cigarette use, therefore, may be markers for more serious patterns of substance use.

Adolescent↗
PubMed1990

Localization of neuropeptide receptor mRNA in rat brain: initial observations using probes for neurotensin and substance P receptors.

The expression of receptors for neurotensin and substance P was examined in rat brain and spinal cord using in situ hybridization with synthetic oligonucleotide probes. Strong hybridization signals for neurotensin receptor mRNA were observed over neurons i.a. in the diagonal band, medial septal nucleus, nucleus basalis magnocellularis, suprachiasmatic nucleus, supramammillary area, substantia nigra and ventral tegmental area. Strong hybridization signals for substance P receptor mRNA were observed over scattered, large neurons in the striatum, and in the spinal cord over neurons in the dorsal horn, the area around the central canal and preganglionic autonomic neurons. Thus, discrete neurons in several brain regions express a G-protein-coupled receptor with which endogenous neurotensin and substance P may interact.

Animals↗
PubMed1976

Time-dependent reaction of human red cell deformability on sphering agents.

The viscosity of samples with normal and normovolemic sphered erythrocytes was tested, using high- and low-shear capillary viscometry, paper filtration of packed red blood cells, and low g-value centrifugation. Incubated serum, pure lysolecithin and bile were used as sphering substances. The initial reaction of the red blood cells with the sphering agents was accompanied by increased viscosities of the blood samples especially at low shear rates. Prolonged storage of the erythrocytes in these media lead to full restoration of normal flow properties.

Bile Acids and Salts↗
PubMedDate not supplied

Fracture-surface analysis of a glaze-strengthened magnesia core material.

The purpose of this research was to study fracture initiation in a glaze-strengthened magnesia ceramic substance used as a core material for all-ceramic crowns. The fracture surfaces of modulus of rupture bars were studied to locate the fracture initiation point. These points were located at the center of hackles that are oriented parallel to the direction of the crack advance. The distance from the fracture initiation point to the surface of the test bars was measured. A direct relationship was found between the flexure strength and the depth of the fracture initiation point. This is consistent with the theory that residual compressive stresses at the glaze-body interface inhibit the spread of flaws and are responsible for the increases in strengths observed.

Crowns↗
PubMed1991

Ethanol absorption across human skin measured by in vivo microdialysis technique.

Microdialysis, a new bioanalytical sampling technique enables measurement of substances in the extracellular space. This initial study investigates the technique's usefulness in the field of percutaneous absorption of solvents, using ethanol as test substance. Microdialysis probes are equipped at the tip with a semi-permeable polycarbonate membrane which permits passive diffusion of substances. Ethanol does not damage the membrane. In vitro recovery for ethanol is good. Probes were inserted via a guide into the skin of the ventral forearm in 7 volunteers. 99.5% ethanol was applied to the skin in excess in a glass reservoir. The probe was perfused at a flow of 1 microliter/min. 50 microliters samples were analysed by gas chromatography. Absorption of ethanol was demonstrated in all subjects. Values from the 9 probes inserted ranged from 10 micrograms/ml to 800 micrograms/ml. The variation may be explained by inter-test or inter-individual variability in ethanol absorption. Individual metabolic capacity may be of importance. The method opens new possibilities in the investigation of skin barrier function in man.

Chromatography, Gas↗
PubMed1979

Concurrent and sequential use of drugs and alcohol: patterns, characteristics of users, and implications for treatment and prevention.

A treatment population of 1,544 drug/alcohol abusers at 10 combined treatment centers was studied to determine the various patterns of sequential use and their corresponding policy implications. Most of the persons who began their substance abuse with alcohol continued to use only alcohol. Alcoholics who did use another substance, either sequentially or concurrently, tended to select a drug other than opiates or marijuana. Although a majority of opiate users eventually became concurrent or sequential users of another substance, a sizable number remained mono-users. A miniscule number of the opiate users moved on to alcohol or marijuana. Most of the users initiated into regular use with marijuana eventually began to use a nonopiate, nonalcoholic substance. A majority of the users who started with a nonalcohol, nonopiate, nonmarijuana substance eventually used marijuana. Sequential and concurrent users in general were more similar to each other than to mono-users. The implications of the development of drug use typologies for direct treatment are discussed. Having identified target groups, the author then suggests policies for controlling substance abuse indirectly, such as those dealing with employment.

Adult↗
PubMed1979

Studies on ocular blood flow and retinal capillary permeability to sodium in pigs.

A surgical technique was developed in pigs that permits access to the retinal venous plexus surrounding the optic nerve. The effect of surgery on ocular blood flow and capillary permeability was evaluated. Blood flow, determined by the labelled microsphere technique, did not differ significantly between operated and control eyes. Increased intraocular pressure in the operated eye reduced blood flow through the choroid and the anterior uvea in proportion to the reduction in perfusion pressure, while in the retina a smaller reduction in blood flow occurred indicating that autoregulatory mechanisms are involved in the control of retinal blood flow. The capillary permeability to sodium was studied by the single injection technique, using albumin as a reference substance. The fractional initial extractions from the choroidal and the retinal vessels were 0.77 and -0.001 respectively. The absence of a sodium extraction from the retinal vessel indicates that this part of the blood-retinal barrier was intact and that the blood drained by the retinal plexus is not mixed with blood from other sources.

Animals↗
PubMed1979

Bone blood flow measured by 85 Sr microspheres and bone seeker clearances in the rat.

This paper investigates further the relationship between the initial bone clearance of a bone-seeking radioisotope or labeled substance and the bone blood flow. The bone blood flow of rats was modified over the widest possible range of physiological values by heating and cooling their hindlimbs. Osseous blood flow was measured by the arteriolar trapping of labeled microspheres of 15 micrometer diameter injected into the left ventricle. The plasma clearances of 45Ca and 99 m Tc by bone were measured 10 min after the intravenous injection of radiocalcium and of 99 m technetium pyrophosphate. The extraction ratio for 45Ca over the 10-min interval (45Ca clearance/bone plasma flow) was 0.60 for low blood flows, 0.40 for blood flows at rest, and 0.25 for high values of flow. The data for 99 m Tc were, respectively, 0.68, 0.34, and 0.22. Initial bone clearances of either substance should not be used to measure the increases in bone blood flow over the values at rest.

Animals↗
PubMed1992

Two-year follow-up of a social-cognitive intervention to prevent substance use.

This study presents two-year follow-up results of the Adolescent Decision-Making Program initially implemented when students were in their sixth grade. The intervention was found to maintain a positive effect on mean tobacco use, but no differences were observed for mean alcohol, marijuana, or hard drug use. In a test of the differential effectiveness of the intervention, program students living with married parents reported lower mean tobacco use than control students living with married parents and program and control students living with single parents. Logistic regression analyses examining the proportion of users at follow-up revealed a negative program effect for alcohol and no differences for the other substances. Subsequent attrition analyses strongly suggested that the positive effect for tobacco use at follow-up was most likely even stronger, and that the negative effect for alcohol was spurious. The importance of examining both program and attrition effects when evaluating the impact of longitudinal preventive interventions was emphasized, and the need to consider alternative models to guide the conceptualization and evaluation of adolescent substance use prevention programs was discussed.

Adolescent↗
PubMed2026

Sex differences in the genetic and causal relationships between depression, smoking, and alcohol use: the role of socioeconomic status.

Major depressive disorder (MDD), smoking, and drinking frequently co-occur, with evidence suggesting these relationships may differ by sex. However, the direction of causality and the extent of sex-specific associations remain unclear. We investigated sex-specific genetic relationships between MDD and substance use phenotypes using genome-wide association studies (GWAS) from the UK Biobank and publicly available sex-stratified GWAS for MDD and problematic alcohol use (PAU). Causal effects were assessed using bidirectional, sex-stratified Mendelian randomization (MR). We further applied multivariable MR (MVMR) to evaluate the influence of socioeconomic status (SES). Genetic correlation analyses indicated significant shared genetic architecture between MDD and all substance use traits in sex-combined GWAS. In sex-specific analyses, the correlation between cigarettes per day and MDD was significantly stronger in females, and drinks per week were correlated with MDD only in females. MR analyses showed that genetic liability to MDD increased the risk of smoking initiation and PAU in females, and was associated with reduced alcohol drinking frequency in males. In contrast, no tested substance use trait showed evidence of a causal effect on MDD in either sex. MVMR adjusting for SES attenuated the association between MDD and smoking initiation. The effect on PAU in females remained. In males, the negative association between MDD and drinking frequency became non-significant after SES adjustment. These findings reveal sex-specific genetic and causal relationships between smoking, drinking, and MDD, and highlight the role of SES as a potential confounder. Incorporating sex and socioeconomic context is critical when examining these associations.

Humans↗
PubMedDate not supplied

[Relationship between avascular necrosis and lipid and purine metabolisms].

The serum levels of uric acid, triglycerides, cholesterol, and lipoproteins were determined in 35 patients suffering from primary avascular necrosis. The results were compared with those of a control group and with those of patients suffering from gout. The frequency distribution of the results in the three groups was of the log-normal type and statistical calculations were made on logarithmic transformations of the serum values. In comparison with the control group, significant increases in the levels of triglycerides, cholesterol, pre-beta-lipoproteins, and uric acid were observed in patients presenting an avascular necrosis. No significant differences were observed between these patients and patients with gout in the levels of lipids and lipoproteins. Uricaemia was higher in the gout patients. Contrary to observations made on the gout patients, there was no correlation in the avascular necrosis patients between the uric acid level and the serum levels of lipids or lipoproteins. In an earlier study the authors put forward an hypothesis according to which the close relationship between the lipid and purine metabolisms in gout patients was due to a genetic linkage based on a common enzyme defect, which directly affected the two metabolisms. In avascular necrosis there is no common enzyme defect; the initial event is a disturbance in the lipid metabolism. The authors conclude with data which tend to show that the bone necrosis observed in patients using steroids or alcohol is not directly induced by these substances, but that once again the initial event is a disturbance in the lipid metabolism.

Adrenal Cortex Hormones↗