Associations between compliance with very low nicotine content (VLNC) cigarettes, abstinence self-efficacy, and quit outcomes in a pilot smoking cessation trial.

BACKGROUND: Switching to Very Low Nicotine Content (VLNC) cigarettes reduces toxicant exposure and nicotine dependence, and may improve smoking cessation. However, non-compliance with VLNCs is often high, which may reduce their effectiveness. Here, we conducted secondary analyses of a pilot smoking cessation trial utilizing VLNCs to examine associations between pre-cessation VLNC compliance and changes in smoking rate, dependence, and abstinence self-efficacy, as well as quit outcomes. METHODS: People who smoke daily (n=35) engaged in a 4-week pre-cessation intervention including VLNCs, transdermal nicotine patch, and behavioral counseling. After quit date, participants received 8 weeks of nicotine replacement therapy and 4 additional behavioral sessions, and were followed for 10 weeks to assess abstinence. Compliance with VLNCs was assessed biweekly during pre-cessation using timeline follow-back. Statistical analyses examined associations between VLNC compliance and a) changes in smoking rate, dependence and abstinence self-efficacy over the course of study cigarette use; and b) time to relapse, controlling for other smoking variables. RESULTS: Greater compliance during the second half of study cigarette use was associated with subsequent improvement in self-efficacy (p<.05). Increased self-efficacy and VLNC compliance both predicted lower likelihood of relapse. Nicotine dependence and cigarettes per day both decreased following study cigarette use, but were unrelated to compliance or relapse. CONCLUSIONS: Compliance with VLNCs prior to quitting increased abstinence self-efficacy and predicted better quit outcomes above and beyond baseline smoking characteristics. Although preliminary, these findings suggest that identifying strategies to promote exclusive use of VLNCs during a brief pre-cessation window may be beneficial.

Large analysis of genetic manipulations reveals an inverse correlation between initial alcohol resistance and rapid tolerance phenotypes.

Tolerance occurs when, following an initial experience with a substance, more of the substance is required subsequently to induce identical behavioral effects. Tolerance is not well-understood, and numerous researchers have turned to model organisms, particularly Drosophila melanogaster, to unravel its mechanisms. Flies have high translational relevance for human alcohol responses, and there is substantial overlap in disease-causing genes between flies and humans, including those associated with Alcohol Use Disorder. Numerous Drosophila tolerance mutants have been described; however, approaches used to identify and characterize these mutants have varied across time and labs and have mostly disregarded any impact of initial resistance/sensitivity to ethanol on subsequent tolerance development. Here, we analyzed our own, as well as data published by other labs to uncover an inverse correlation between initial ethanol resistance and tolerance phenotypes. This inverse correlation suggests that initial resistance phenotypes can explain many 'perceived' tolerance phenotypes, thus classifying such mutants as 'secondary' tolerance mutants. Additionally, we show that tolerance should be measured as a relative increase in time to sedation between an initial and second exposure rather than an absolute change in time to sedation. Finally, based on our analysis, we provide a method for using a linear regression equation to assess the residuals of potential tolerance mutants. These residuals provide predictive insight into the likelihood of a mutant being a 'primary' tolerance mutant, where a tolerance phenotype is not solely a consequence of initial resistance, and we offer a framework for understanding the relationship between initial resistance and tolerance.

Probing the Paradox: Investigating the Impact of Affect, Exercise Type, and Cannabis Use on the Alcohol-Exercise Relationship in College Students.

Alcohol has previously shown a paradoxical positive relationship with exercise behaviors. However, the relationship has not been explored according to type of exercise (aerobic vs. anaerobic), nor has the research considered other contextual variables that commonly co-occur with alcohol use, such as cannabis and mood. This study sought to expand upon previous research to understand how the alcohol-exercise relationship may vary based on exercise type. Additionally, this study included cannabis use and mood as moderators of the alcohol-exercise association. Cross-sectional survey data was collected from college students (N = 335). Negative binomial regression was used to test associations between exercise and alcohol consumption, cannabis use, positive affect (PA), negative affect (NA), and moderating effects of these factors on the alcohol-exercise relationship. Effect sizes are reported from an Incidence Rate Ratio (IRR). Sex assigned at birth (male = 1, female = 0; IRR = 1.34, p = .017), PA (IRR = 1.57, p = .001), and alcohol consumption (IRR = 1.94, p = .037) exhibited positive relationships with exercise. Significant main effects were not observed for negative affect (IRR = 1.17, p = .230), or cannabis use (IRR = 1.00, p = .988). There was a significant interaction between positive affect and alcohol consumption (IRR = 0.87, p = .044) predicting exercise minutes. Alcohol was positively associated with exercise for those with low positive affect (n = 42, b = 12.61, p = .096) and this effect was attenuated as levels of positive affect increased (mean positive affect: n = 232, b = 0.55, p = .926; high positive affect: n = 61, b = -15.86, p = .146). These findings suggest that low positive affect may contribute to the positive link between alcohol use and exercise (especially aerobic exercise) in young people.

Bariatric surgery: trends in utilization, complications, conversions and revisions.

BACKGROUND: Sleeve gastrectomy (SG) increased in popularity after 2010 but recent data suggest it has concerning rates of gastroesophageal reflux and need for conversions. This study aims to evaluate recent trends in the utilization of bariatric procedures, associated complications, and conversions using an administrative claims database in the United States. METHODS: We included adults who had bariatric procedures from 2000 to 2020 with continuous enrollment for at least 6 months in the MarketScan Commercial Claims and Encounters database. Index bariatric procedures and subsequent revisions or conversions were identified using CPT codes. Baseline comorbidities and postoperative complications were identified with ICD-9-CM and ICD-10 codes. Cumulative incidences of complications were estimated at 30-days, 6-months, and 1-year and compared with stabilized inverse probability of treatment weighted Kaplan-Meier analysis. RESULTS: We identified 349,411 bariatric procedures and 5521 conversions or revisions. The sampled SG volume appeared to begin declining in 2018 while Roux-en-Y gastric bypass (RYGB) remained steady. Compared to RYGB, SG was associated with lower 1-year incidence [aHR, (95% CIs)] for 30-days readmission [0.65, (0.64-0.68)], dehydration [0.75, (0.73-0.78)], nausea or vomiting [0.70, (0.69-0.72)], dysphagia [0.55, (0.53-0.57)], and gastrointestinal hemorrhage [0.43, (0.40-0.46)]. Compared to RYGB, SG was associated with higher 1-year incidence [aHR, (95% CIs)] of esophagogastroduodenoscopy [1.13, (1.11-1.15)], heartburn [1.38, (1.28-1.49)], gastritis [4.28, (4.14-4.44)], portal vein thrombosis [3.93, (2.82-5.48)], and hernias of all types [1.36, (1.34-1.39)]. There were more conversions from SG to RYGB than re-sleeving procedures. SG had a significantly lower 1-year incidence of other non-revisional surgical interventions when compared to RYGB. CONCLUSIONS: The overall volume of bariatric procedures within the claims database appeared to be declining over the last 10 years. The decreasing proportion of SG and the increasing proportion of RYGB suggest the specific complications of SG may be driving this trend. Clearly, RYGB should remain an important tool in the bariatric surgeon's armamentarium.

Cryptic diversity in southern African kelp.

The southern coast of Africa is one of the few places in the world where water temperatures are predicted to cool in the future. This endemism-rich coastline is home to two sister species of kelps of the genus Ecklonia maxima and Ecklonia radiata, each associated with specific thermal niches, and occuring primarily on opposite sides of the southern tip of Africa. Historical distribution records indicate that E. maxima has recently shifted its distribution ~ 70 km eastward, to sites where only E. radiata was previously reported. The contact of sister species with contrasting thermal affinities and the occurrence of mixed morphologies raised the hypothesis that hybridization might be occurring in this contact zone. Here we describe the genetic structure of the genus Ecklonia along the southern coast of Africa and investigate potential hybridization and cryptic diversity using a combination of nuclear microsatellites and mitochondrial markers. We found that both species have geographically discrete genetic clusters, consistent with expected phylogeographic breaks along this coastline. In addition, depth-isolated populations were found to harbor unique genetic diversity, including a third Ecklonia lineage. Mito-nuclear discordance and high genetic divergence in the contact zones suggest multiple hybridization events between Ecklonia species. Discordance between morphological and molecular identification suggests the potential influence of abiotic factors leading to convergent phenotypes in the contact zones. Our results highlight an example of cryptic diversity and hybridization driven by contact between two closely related keystone species with contrasting thermal affinities.

Heterogeneity of tethered agonist signaling in adhesion G protein-coupled receptors.

Adhesion G protein-coupled receptor (aGPCR) signaling influences development and homeostasis in a wide range of tissues. In the current model for aGPCR signaling, ligand binding liberates a conserved sequence that acts as an intramolecular, tethered agonist (TA), yet this model has not been evaluated systematically for all aGPCRs. Here, we assessed the TA-dependent activities of all 33 aGPCRs in a suite of transcriptional reporter, G protein activation, and ß-arrestin recruitment assays using a new fusion protein platform. Strikingly, only ∼50% of aGPCRs exhibited robust TA-dependent activation, and unlike other GPCR families, aGPCRs showed a notable preference for G12/13 signaling. AlphaFold2 predictions assessing TA engagement in the predicted intramolecular binding pocket aligned with the TA dependence of the cellular responses. This dataset provides a comprehensive resource to inform the investigation of all human aGPCRs and for targeting aGPCRs therapeutically.

Knowledge, attitude, and practice of insulin among diabetic patients and pharmacists in Egypt: "cross-sectional observational study".

BACKGROUND: Diabetes recently has been identified as a growing epidemic. Although insulin's vital role in both types of diabetes, it is considered one of the harmful medications if used incorrectly. In Egypt, effective usage of insulin remains a challenge due to insufficient knowledge of insulin and diabetes management, leading to errors in insulin therapy. As pharmacists are experts in pharmacological knowledge, they are uniquely situated to assess adherence to treatment regimens, the effect of drug therapy, or potential alterations in drug therapy to meet patient goals. To provide effective patient education and counseling, community pharmacists in Egypt should be efficiently knowledgeable about diabetes and insulin. OBJECTIVE: To identify the knowledge, attitude, and practice of pharmacists and patients about insulin. To identify pharmacists' educational preparedness and confidence in counseling diabetic patients. METHODS: A descriptive, cross-sectional study was conducted with two knowledge, attitude, and practice surveys. This study was carried out from September 2016 to February 2023. Face-to-face interviews were conducted with patients, and a paper-based questionnaire was administered to pharmacists. The two questionnaires were adapted from previous studies. RESULTS: A total of 492 patients and 465 pharmacists participated in this study. The mean knowledge score of correct answers among patients and pharmacists was 10.67 ± 1.9 and 15 ± 3.6. Most of the patients and pharmacists had a positive attitude regarding insulin's role in improving health and to better control blood glucose. On the negative side, around half of the patients reported that they believe that regular use of insulin leads to addiction, while only 14.5% of the pharmacists believed that insulin could cause addiction. Self-confidence scores for pharmacists differed statistically with sex, years of experience, and pharmacist's direct exposure to diabetic patients. CONCLUSIONS: This study uncovers considerable deficiencies in patients' and pharmacists' knowledge about insulin therapy. This study also strongly recommends higher education and a more structured pharmacist training schedule.

Highly Concentrated Linear Guanidine Amides from the Marine Sipunculid Phascolosoma granulatum.

The chemical diversity of annelids, particularly those belonging to the class Sipuncula, remains largely unexplored. However, as part of a Marine Biodiscovery program in Ireland, the peanut worm Phascolosoma granulatum emerged as a promising source of unique metabolites. The purification of the MeOH/CH2Cl2 extract of this species led to the isolation of six new linear guanidine amides, named phascolosomines A-F (1-6). NMR analysis allowed for the elucidation of their structures, all of which feature a terminal guanidine, central amide linkage, and a terminal isobutyl group. Notably, these guanidine amides were present in unusually high concentrations, comprising ∼3% of the dry mass of the organism. The primary concentration of the phascolosomines in the viscera is similar to that previously identified in linear amides from sipunculid worms and marine fireworms. The compounds from sipunculid worms have been hypothesized to be toxins, while those from fireworms are reported to be defensive irritants. However, screening of the newly isolated compounds for inhibitory bioactivity showed no significant inhibition in any of the assays conducted.

Impacts of compounding drought and heatwave events on child mental health: insights from a spatial clustering analysis.

BACKGROUND: Concurrent heatwave and drought events may have larger health impacts than each event separately; however, no US-based studies have examined differential mental health impacts of compound drought and heatwave events in pediatric populations. OBJECTIVE: To examine the spatial patterns of mood disorders and suicide-related emergency department (ED) visits in children during heatwave, drought, and compound heatwave and drought events. We tested whether the occurrence of compound heatwave and drought events have a synergistic (multiplicative) effect on the risk of mental health related outcomes in children as compared to the additive effect of each individual climate hazard. Lastly, we identified household and community-level determinants of geographic variability of high psychiatric burden. METHODS: Daily counts of psychiatric ED visits in North Carolina from 2016 to 2019 (May to Sept) for pediatric populations were aggregated at the county scale. Bernoulli cluster analyses identified high-risk spatial clusters of psychiatric morbidity during heatwave, drought, or compound heatwave and drought periods. Multivariate adaptive regression models examined the individual importance of household and community-level determinants in predicting high-risk clustering of mood disorders or suicidality across the three climate threats. RESULTS: Results showed significant spatial clustering of suicide and mood disorder risks in children during heatwave, drought, and compound event periods. Periods of drought were associated with the highest likelihood of spatial clustering for suicide and mood disorders, where the risk of an ED visit was 4.48 and 6.32 times higher, respectively, compared to non-drought periods. Compounding events were associated with a threefold increase in both suicide and mood disorder-related ED visits. Community and household vulnerability factors that most contributed to spatial clustering varied across climate hazards, but consistent determinants included residential segregation, green space availability, low English proficiency, overcrowding, no broadband access, no vehicle access, housing vacancy, and availability of housing units. CONCLUSION: Findings advance understanding on the locations of vulnerable pediatric populations who are disproportionately exposed to compounding climate stressors and identify community resilience factors to target in public health adaptation strategies.

Effect of Lifestyle on Reducing Risk Factors for Type 2 Diabetes among Arab Canadian Muslim Women: A Randomized Control Trial.

PURPOSE: This study aimed to investigate whether modifiable risk factors for type 2 diabetes (T2D) can be reduced by an intensive healthy lifestyle intervention designed for Arab Muslim women of Middle Eastern descent (AWMD) who are at high risk for this disease. We hypothesized that among Canadian AWMD, the intervention would (a) reduce the identified health risk factors for T2D (body mass index [BMI], ≥30 kg·m-2; fasting blood glucose [FBG], ≥5.6 mmol·L-1; and waist circumference [WC], ≥80 cm); (b) improve anthropometric measurements; (c) improve lifestyle factors (physical activity level [steps per day] and dietary habits); and (d) improve cardiovascular fitness and reduce blood pressure. METHODS: After informed consent, 60 participants were randomized to either an exercise and nutrition group (ENG; n = 30) or a control group (CON; n = 30). ENG attended a women-only supervised exercise program that presented Arabic music and traditional Lebanese Dabka three times a week in a Mosque gym for 12 wk. A nutritionist was available 1 h·wk-1 for nutrition education. The CON followed their typical day. RESULTS: ENG and CON had similar increased risk profiles for diabetes at baseline. Large significant pre/posttreatment interaction effects were found for BMI, FBG, and WC with a reduced diabetes risk for ENG compared with CON for BMI (1,58) = 1184.8, P < 0.001), FBG (1,58) = 187.7, P < 0.001), and WC (1,58) = 326.4, P < 0.001). The ENG had significantly more participants reach postintervention target values (BMI: χ2(1) = 16.48, P = 0.001; FBG: χ2(1) = 52.26, P < 0.001; WC: χ2(1) = 4.29, P = 0.038) compared with the CON. Adherence to the program was 100%. CONCLUSIONS: Modifiable risk factors for T2D were reduced by using a culturally sensitive intervention program with high adherence through weight loss, regular exercise, and nutrition education.

Diagnostic Utility of Restriction Spectrum Imaging in Head and Neck Tumors: A Pilot Study.

OBJECTIVE: Imaging is crucial in the assessment of head and neck cancers for site, extension, and enlarged lymph nodes. Restriction spectrum imaging (RSI) is a new diffusion-weighted magnetic resonance imaging (MRI) technique that enhances the ability to differentiate aggressive cancer from low-grade or benign tumors and helps guide treatment and biopsy. Its contribution to imaging of brain and prostate tumors has been previously published. However, there are no prior studies using RSI sequence in head and neck tumors. The purpose of this study was to evaluate the feasibility of performing RSI in head and neck cancer. METHODS: An additional RSI sequence was added in the routine MRI neck protocol for 13 patients diagnosed with head and neck cancer between November 2018 and April 2019. Restriction spectrum imaging sequence was performed with b values of 0, 500, 1500, and 3000 s/mm 2 and 29 directions on 1.5T magnetic resonance scanners.Diffusion-weighted imaging (DWI) images and RSI images were compared according to their ability to detect the primary malignancy and possible metastatic lymph nodes. RESULTS: In 71% of the patients, RSI outperformed DWI in detecting the primary malignancy and possible metastatic lymph nodes, whereas in the remaining cases, the 2 were comparable. In 66% of the patients, RSI detected malignant lymph nodes that DWI/apparent diffusion coefficient failed to detect. CONCLUSIONS: This is the first study of RSI in head and neck imaging and showed its superiority over the conventional DWI sequence. Because of its ability to differentiate benign and malignant lymph nodes in some cases, the addition of RSI to routine head and neck MRI should be considered.

Functional profiling of the G protein-coupled receptor C3aR1 reveals ligand-mediated biased agonism.

G protein-coupled receptors (GPCRs) are leading druggable targets for several medicines, but many GPCRs are still untapped for their therapeutic potential due to poor understanding of specific signaling properties. The complement C3a receptor 1 (C3aR1) has been extensively studied for its physiological role in C3a-mediated anaphylaxis/inflammation, and in TLQP-21-mediated lipolysis, but direct evidence for the functional relevance of the C3a and TLQP-21 ligands and signal transduction mechanisms are still limited. In addition, C3aR1 G protein coupling specificity is still unclear, and whether endogenous ligands, or drug-like compounds, show ligand-mediated biased agonism is unknown. Here, we demonstrate that C3aR1 couples preferentially to Gi/o/z proteins and can recruit ß-arrestins to cause internalization. Furthermore, we showed that in comparison to C3a63-77, TLQP-21 exhibits a preference toward Gi/o-mediated signaling compared to ß-arrestin recruitment and internalization. We also show that the purported antagonist SB290157 is a very potent C3aR1 agonist, where antagonism of ligand-stimulated C3aR1 calcium flux is caused by potent ß-arrestin-mediated internalization. Finally, ligand-mediated signaling bias impacted cell function as demonstrated by the regulation of calcium influx, lipolysis in adipocytes, phagocytosis in microglia, and degranulation in mast cells. Overall, we characterize C3aR1 as a Gi/o/z-coupled receptor and demonstrate the functional relevance of ligand-mediated signaling bias in key cellular models. Due to C3aR1 and its endogenous ligands being implicated in inflammatory and metabolic diseases, these results are of relevance toward future C3aR1 drug discovery.

Ledipasvir/Sofosbuvir in Hepatitis C Virus-Infected Children With Hematological Malignancies: A Pharmacokinetic Study.

PURPOSE: Children with hematological malignancies and chronic hepatitis C virus (HCV) infection are at a higher risk for rapid progression of liver disease and malignancy relapse due to multiple hepatitis flares and chemotherapy interruption. They are therefore potential candidates for microelimination of HCV infection. This study aimed to assess the effect of acute lymphoblastic leukemia (ALL) on the pharmacokinetic (PK) profile of direct-acting antivirals, namely ledipasvir/sofosbuvir (LDV/SOF) and the SOF major metabolite GS-331007. METHODS: This was a 24-week, prospective, controlled, open-label, 2-arm PK study of patients receiving 45/200 mg once-daily LDV/SOF orally for 12 weeks. Eligible patients were HCV-RNA-positive, treatment-naive children aged 6 to <12 years and/or weighing 17 to <35 kg with genotype 4 chronic HCV infection without cirrhosis. The primary efficacy and safety end points were the achievement of sustained virologic response for all patients with absence of any adverse events leading to permanent discontinuation of the study drug. Steady-state noncompartmental analysis was performed to determine the PK parameters of SOF, GS-331007, and LDV as the primary PK outcome. Dose suitability was based on the 90% CI of exposure geometric mean ratio percentage within 50% to 200% compared with adults. FINDINGS: Ten HCV-infected children with ALL (chemotherapy treatment group) and 12 eligible children with no malignancy (control group) were enrolled and completed the study period. All 22 patients achieved the sustained virologic response with no adverse events leading to interruption or permanent discontinuation of the study drug. Compared with the control group, the ALL group patients had similar SOF, GS-331007, and LDV exposure. Compared with adults, the AUCτ of GS-331007 was lower and the AUCτ and Cmax,ss of SOF and the Cmax,ss of LDV were modestly higher in the ALL group (acceptance limit, 50%-200%). However, the observed efficacy and favorable safety profile made these changes not clinically significant. IMPLICATIONS: Weight-based dosing of LDV/SOF (45/200 mg) is highly effective and safe among genotype 4 HCV-infected children weighing 17 to <35 kg and diagnosed with ALL undergoing maintenance chemotherapy. The similarity in the drug exposure, efficacy, and safety clinical end points between patients with and without hematological malignancy support their therapeutic equivalence. Further studies with a larger sample size may be required to confirm the safety of LDV/SOF in patients with ALL and to recommend appropriate dosing in children with hematological malignancies, if needed. CLINICALTRIALS: gov identifier: NCT03903185.

Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential.

Serotonergic psychedelics possess considerable therapeutic potential. Although 5-HT2A receptor activation mediates psychedelic effects, prototypical psychedelics activate both 5-HT2A-Gq/11 and ß-arrestin2 transducers, making their respective roles unclear. To elucidate this, we develop a series of 5-HT2A-selective ligands with varying Gq efficacies, including ß-arrestin-biased ligands. We show that 5-HT2A-Gq but not 5-HT2A-ß-arrestin2 recruitment efficacy predicts psychedelic potential, assessed using head-twitch response (HTR) magnitude in male mice. We further show that disrupting Gq-PLC signaling attenuates the HTR and a threshold level of Gq activation is required to induce psychedelic-like effects, consistent with the fact that certain 5-HT2A partial agonists (e.g., lisuride) are non-psychedelic. Understanding the role of 5-HT2A Gq-efficacy in psychedelic-like psychopharmacology permits rational development of non-psychedelic 5-HT2A agonists. We also demonstrate that ß-arrestin-biased 5-HT2A receptor agonists block psychedelic effects and induce receptor downregulation and tachyphylaxis. Overall, 5-HT2A receptor Gq-signaling can be fine-tuned to generate ligands distinct from classical psychedelics.

Additional Sarasinosides from the Marine Sponge Melophlus sarasinorum Collected from the Bismarck Sea.

In our continuing efforts to describe the biological and chemical diversity of sponges from Kimbe Bay, Papua New Guinea, the known 30-norlanostane saponin sarasinoside C1 (1) was identified along with six new analogues named sarasinosides C4, C5, C6, C7, C8, and C9 (2-7) from the sponge Melophlus sarasinorum. The structures of the new compounds were elucidated by analysis of 1D and 2D NMR and HRMS data, as well as comparison with literature data. All new compounds are characterized by the same tetraose moiety, ß-d-Xylp-(1→6)-ß-d-GlcNAcp-(1→2)-[ß-d-GalNAcp-(1→4)]-ß-d-Xylp, as described previously for sarasinoside C1, but differed in their aglycone moieties. When comparing NMR data of sarasinoside C8 with those of known analogues, a misassignment was identified in the configuration of the C-8/C-9 diol for the previously described sarasinoside R (8), and it has been corrected here using a combination of ROESY analysis and molecular modeling.

Large genetic analysis of alcohol resistance and tolerance reveals an inverse correlation and suggests 'true' tolerance mutants.

Tolerance occurs when, following an initial experience with a substance, more of the substance is required subsequently to induce the same behavioral effects. Tolerance is historically not well-understood, and numerous researchers have turned to model organisms, particularly Drosophila melanogaster, to unravel its mechanisms. Flies have high translational relevance for human alcohol responses, and there is substantial overlap in disease-causing genes between flies and humans, including those associated with Alcohol Use Disorder. Numerous Drosophila tolerance mutants have been described; however, approaches used to identify and characterize these mutants have varied across time and between labs and have mostly disregarded any impact of initial resistance/sensitivity to ethanol on subsequent tolerance development. Here, we have analyzed a large amount of data - our own published and unpublished data and data published by other labs - to uncover an inverse correlation between initial ethanol resistance and tolerance phenotypes. This inverse correlation suggests that initial resistance phenotypes can explain many 'perceived' tolerance phenotypes. Additionally, we show that tolerance should be measured as a relative increase in time to sedation between an initial and second exposure rather than an absolute change in time to sedation. Finally, based on our analysis, we provide a method for using a linear regression equation to assess the residuals of potential tolerance mutants. We show that these residuals provide predictive insight into the likelihood of a mutant being a 'true' tolerance mutant, and we offer a framework for understanding the relationship between initial resistance and tolerance.

Activation of mTOR signaling in adult lung microvascular progenitor cells accelerates lung aging.

Reactivation and dysregulation of the mTOR signaling pathway are a hallmark of aging and chronic lung disease; however, the impact on microvascular progenitor cells (MVPCs), capillary angiostasis, and tissue homeostasis is unknown. While the existence of an adult lung vascular progenitor has long been hypothesized, these studies show that Abcg2 enriches for a population of angiogenic tissue-resident MVPCs present in both adult mouse and human lungs using functional, lineage, and transcriptomic analyses. These studies link human and mouse MVPC-specific mTORC1 activation to decreased stemness, angiogenic potential, and disruption of p53 and Wnt pathways, with consequent loss of alveolar-capillary structure and function. Following mTOR activation, these MVPCs adapt a unique transcriptome signature and emerge as a venous subpopulation in the angiodiverse microvascular endothelial subclusters. Thus, our findings support a significant role for mTOR in the maintenance of MVPC function and microvascular niche homeostasis as well as a cell-based mechanism driving loss of tissue structure underlying lung aging and the development of emphysema.

Case of Accidental Trauma Resulting in Condylar Fractures in 3-Month-Old.

While mandibular fractures represent the most common craniofacial injury in the pediatric population, craniofacial fractures in infants are rare. Diagnosis is challenging with nonspecific presenting symptoms and often limited radiographic imaging. We report a case of nondisplaced mandibular condylar head fractures in a 3-month-old patient as a result of a fall with impact onto the chin, with associated sublingual hematoma (Coleman's sign). Although the initially observed sole finding of sublingual hematoma raised concern for child physical abuse, detailed history, oral exam, and multidisciplinary review of radiologic records by pediatrics, otolaryngology, and child protection teams established the accidental trauma diagnosis. The patient was managed conservatively with normal resumption of feeding. Detailed history and multidisciplinary approach to the management of pediatric facial trauma are important in establishing diagnoses and management.

Resolving the identity of commercially cultivated Ulva (Ulvaceae, Chlorophyta) in integrated seaweed-abalone aquaculture farms in South Africa.

Species of Ulva have a wide range of commercial applications and are increasingly being recognized as promising candidates for integrated aquaculture. In South Africa, Ulva has been commercially cultivated in integrated seaweed-abalone aquaculture farms since 2002, with more than 2000 tonnes of biomass cultivated per annum in land-based paddle raceways. However, the identity of the species of Ulva grown on these farms remains uncertain. We therefore characterized samples of Ulva cultivated in five integrated multi-trophic aquaculture farms (IMTA) across a wide geographical range and compared them with foliose Ulva specimens from neighboring seashores. The molecular markers employed for this study were the chloroplast-encoded Ribulose-1,5-bisphosphate carboxylase oxygenase (rbcL), the Internal Transcribed Spacer (ITS) of the nuclear, and the chloroplast elongation factor tufA. All currently cultivated specimens of Ulva were molecularly resolved as a single species, U. lacinulata. The same species has been cultivated for over a decade, although a few specimens of two other species were also present in early South African IMTA systems. The name Ulva uncialis is adopted for the Ulva "Species A" by Fort et al. (2021), Molecular Ecology Resources, 22, 86) significantly extending the distribution range for this species. A comparison with wild Ulva on seashores close to the farms resulted in five new distribution records for South Africa (U. lacinulata, U. ohnoi, U. australis, U. stenophylloides, and U. aragoënsis), the first report of a foliose form of U. compressa in the region, and one new distribution record for Namibia (U. australis). This study reiterates the need for DNA confirmation, especially when identifying morphologically simple macroalgae with potential commercial applications.