Administration of a Cannabinoid Receptor Antagonist Following Chronic ∆\u3csup\u3e9\u3c/sup\u3e-Tetrahydrocannabinol Induces Physical Withdrawal in the Absence of a Dysphoric State

The selective cannabinoid CB1 receptor antagonist SR141716 has been shown to precipitate physical signs of withdrawal in ∆9-tetrahydrocannabinol (THC)-dependent rats; however, the affective state associated with this withdrawal state has not yet been well characterized. Thus, the aim of present study was to examine the physical and affective consequences of SR141716-precipitated THC withdrawal in male Sprague-Dawley rats. Rats were injected with THC (5 mg/kg, i.p.) or its vehicle twice daily for 13 consecutive days, and challenged with SRI 41716 (1 mg/kg, i.p.) or its vehicle 1 h later on days 3, 5, 7, 9, 11, and 13. Consistent with previous reports, SR141716 induced signs of physical withdrawal (e.g., increased scratching) in THC-dependent animals. The affective state induced by both SR141716-precipitated THC withdrawal and naloxoneprecipitated morphine withdrawal were then assessed using a tactile cue-conditioning paradigm, and withdrawal-induced anxiety was measured using a test battery consisting of the emergence test, elevated plus maze (EPM), and social interaction test. Precipitated morphine withdrawal induced both significant conditioned cue avoidance and anxiogenic-like behaviour; however, precipitated THC withdrawal failed to produce a conditioned cue avoidance, and did not induce anxiety in a manner different from that produced by administration of THC alone. These findings provide novel evidence that unlike opiate withdrawal, cannabinoid withdrawal manifests physical signs of withdrawal, but does not induce anxiety or a dysphoric state. Although there may be overt physical similarities between opiate and cannabinoid withdrawal, these syndromes likely represent distinct emotional and subjective states

Administration of a Cannabinoid Receptor Antagonist Following Chronic ∆\u3csup\u3e9\u3c/sup\u3e-Tetrahydrocannabinol Induces Physical Withdrawal in the Absence of a Dysphoric State

The selective cannabinoid CB1 receptor antagonist SR141716 has been shown to precipitate physical signs of withdrawal in ∆9-tetrahydrocannabinol (THC)-dependent rats; however, the affective state associated with this withdrawal state has not yet been well characterized. Thus, the aim of present study was to examine the physical and affective consequences of SR141716-precipitated THC withdrawal in male Sprague-Dawley rats. Rats were injected with THC (5 mg/kg, i.p.) or its vehicle twice daily for 13 consecutive days, and challenged with SRI 41716 (1 mg/kg, i.p.) or its vehicle 1 h later on days 3, 5, 7, 9, 11, and 13. Consistent with previous reports, SR141716 induced signs of physical withdrawal (e.g., increased scratching) in THC-dependent animals. The affective state induced by both SR141716-precipitated THC withdrawal and naloxoneprecipitated morphine withdrawal were then assessed using a tactile cue-conditioning paradigm, and withdrawal-induced anxiety was measured using a test battery consisting of the emergence test, elevated plus maze (EPM), and social interaction test. Precipitated morphine withdrawal induced both significant conditioned cue avoidance and anxiogenic-like behaviour; however, precipitated THC withdrawal failed to produce a conditioned cue avoidance, and did not induce anxiety in a manner different from that produced by administration of THC alone. These findings provide novel evidence that unlike opiate withdrawal, cannabinoid withdrawal manifests physical signs of withdrawal, but does not induce anxiety or a dysphoric state. Although there may be overt physical similarities between opiate and cannabinoid withdrawal, these syndromes likely represent distinct emotional and subjective states

UT researchers study why certain groups don't trust public health information on COVID

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Hip Strengthening Compared With Quadriceps Strengthening in Conservative Treatment of Patients With Patellofemoral Pain: A Critically Appraised Topic

Clinical Scenario: Patellofemoral pain is a common injury that affects both athletic and sedentary populations. Clinicians may treat patellofemoral pain more effectively through a comprehensive understanding of the most effective exercise protocols. Clinical Question: In patients with patellofemoral pain, are hip abductor and external rotator muscle strengthening exercises more effective in reducing pain and improving patient-reported function compared with isolated quadriceps strengthening? Summary of Key Findings: A comprehensive and systematic database search was conducted for studies of level 2 evidence or higher. The search yielded 253 studies; of these studies, four randomized control trials and one comparative control trial fit the inclusion and exclusion criteria. A combination of quadriceps and hip strengthening exercises or hip strengthening exercises alone reduced pain and improved patient-reported function compared with quadriceps strengthening alone. Clinical Bottom Line: There is strong evidence to support the use of hip strengthening or hip strengthening combined with quadriceps strengthening in the treatment of patellofemoral pain to decrease pain and improve patient reported function. Strength of Recommendation: The Strength of Recommendation Taxonomy recommends a grade of A for level 1 evidence with consistent patient-oriented findings

Evaluating Pharmaceutical Sorption to Soils and Ground Water from an Eastern North Carolinian Family Farm

The fate and transport of pharmaceuticals through soil and ground water is an important research topic because of their possible toxic environmental effects. Representative sites are often used for testing the probability of acompound to adsorb to the soil or spread within the groundwater. In this study, the Brisson Farm in North Carolina was selected as a representative site due to the recent disposal of multiple pharmaceuticals into the septic tank on the property and the lack of organic carbon in the soil. This research used batch experiments to calculate sorption coefficients for various pharmaceuticals that were disposed of on August 24, 2012. It is commonly thought thatorganic carbon content is the key factor in determining the fate of such chemicals. Data from this study provides evidence that soil minerals have a distinct role in the adsorption, fate, and transport of a medication. Results fromthe Brisson Farm were compared to other representative soils in the mountains of Western North Carolina and various soil components

Bone mineral density among men and women aged 35 to 50 years

© 2019 American Osteopathic Association. Context: Osteoporosis is characterized by low bone mineral density (BMD) and has been thought to only be a major health concern for postmenopausal women. However, osteoporosis and its risk factors have been greatly understudied in the middle-aged and male populations. Objective: To assess the likelihood of low BMD and its association with related risk factors in early–middle-aged (defined in this study as 35-50 years) men and women.Methods: Eligible men and women completed a questionnaire assessing calcium intake, hours per week of exercise, and other related risk factors associated with osteoporosis and osteopenia. The primary outcome variable, BMD, was attained using dual-energy x-ray absorptiometry scans taken at the femoral neck, trochanter, intertrochanteric crest, total femur, and lumbar spine.Results: Of the 173 participants in this study, 23 men (28%) and 24 women (26%) had osteopenia at the femoral neck. In men, there was a significant and negative correlation between exercise and femoral neck BMD (r=−0.296, P=.01). In women, correlation analyses showed significant positive correlations between exercise and BMD of the trochanter (r=0.329, P=.003), intertrochanteric crest (r=0.285, P=.01), total femur (r=0.30, P=.01), and lumbar spine (r=0.29, P=.01).Conclusions: Osteopenia was found in more than 25% of both male and female participants, which suggests that more osteoporosis screening and prevention programs need to be targeted to persons in the studied age group because osteopenia can lead to osteoporosis

Widespread genetic heterogeneity of human ribosomal RNA genes

Polymorphism drives survival under stress and provides adaptability. Genetic polymorphism of ribosomal RNA (rRNA) genes derives from internal repeat variation of this multicopy gene, and from interindividual variation. A considerable amount of rRNA sequence heterogeneity has been proposed but has been challenging to estimate given the scarcity of accurate reference sequences. We identified four rDNA copies on chromosome 21 (GRCh38) with 99% similarity to recently introduced reference sequence KY962518.1. We customized a GATK bioinformatics pipeline using the four rDNA loci, spanning a total 145 kb, for variant calling and used high-coverage whole-genome sequencing (WGS) data from the 1000 Genomes Project to analyze variants in 2504 individuals from 26 populations. We identified a total of 3791 variant positions. The variants positioned nonrandomly on the rRNA gene. Invariant regions included the promoter, early 5 ' ETS, most of 18S, 5.8S, ITS1, and large areas of the intragenic spacer. A total of 470 variant positions were observed on 28S rRNA. The majority of the 28S rRNA variants were located on highly flexible human-expanded rRNA helical folds ES7L and ES27L, suggesting that these represent positions of diversity and are potentially under continuous evolution. Several variants were validated based on RNA-seq analyses. Population analyses showed remarkable ancestry-linked genetic variance and the presence of both high penetrance and frequent variants in the 5 ' ETS, ITS2, and 28S regions segregating according to the continental populations. These findings provide a genetic view of rRNA gene array heterogeneity and raise the need to functionally assess how the 28S rRNA variants affect ribosome functions.Peer reviewe

Two cases of Kerstersia gyiorum isolated from sites of chronic infection

Kerstersia gyiorum is infrequently associated with human infection. We report the isolation of Kerstersia gyiorum from two patients: the first, a patient with chronic ear infections, and the second, a patient with a chronic leg wound. Both isolates were resistant to ciprofloxacin, which has not been previously reported

Identification of an E3 ligase that targets the catalytic subunit of RNA Polymerase I upon transcription stress

Publisher Copyright: © 2022 The AuthorsRNA Polymerase I (Pol I) synthesizes rRNA, which is the first and rate-limiting step in ribosome biogenesis. Factors governing the stability of the polymerase complex are not known. Previous studies characterizing Pol I inhibitor BMH-21 revealed a transcriptional stress-dependent pathway for degradation of the largest subunit of Pol I, RPA194. To identify the E3 ligase(s) involved, we conducted a cell-based RNAi screen for ubiquitin pathway genes. We establish Skp–Cullin–F-box protein complex F-box protein FBXL14 as an E3 ligase for RPA194. We show that FBXL14 binds to RPA194 and mediates RPA194 ubiquitination and degradation in cancer cells treated with BMH-21. Mutation analysis in yeast identified lysines 1150, 1153, and 1156 on Rpa190 relevant for the protein degradation. These results reveal the regulated turnover of Pol I, showing that the stability of the catalytic subunit is controlled by the F-box protein FBXL14 in response to transcription stress.Peer reviewe

The PhanSST global database of Phanerozoic sea surface temperature proxy data

Paleotemperature proxy data form the cornerstone of paleoclimate research and are integral to understanding the evolution of the Earth system across the Phanerozoic Eon. Here, we present PhanSST, a database containing over 150,000 data points from five proxy systems that can be used to estimate past sea surface temperature. The geochemical data have a near-global spatial distribution and temporally span most of the Phanerozoic. Each proxy value is associated with consistent and queryable metadata fields, including information about the location, age, and taxonomy of the organism from which the data derive. To promote transparency and reproducibility, we include all available published data, regardless of interpreted preservation state or vital effects. However, we also provide expert-assigned diagenetic assessments, ecological and environmental flags, and other proxy-specific fields, which facilitate informed and responsible reuse of the database. The data are quality control checked and the foraminiferal taxonomy has been updated. PhanSST will serve as a valuable resource to the paleoclimate community and has myriad applications, including evolutionary, geochemical, diagenetic, and proxy calibration studies