The Reddit cannabis subjective highness rating scale: Applying computational social science to explore psychological and environmental correlates of naturalistic cannabis use.

Social media data provide unprecedented access to discussions of active, naturalistic, and often real-time cannabis use in an era of cannabis policy liberalization. The aim of this study was to explore psychological and environmental correlates of cannabis effects by applying computational social science approaches to a large dataset of unprompted reports of naturalistic cannabis use with corresponding self-reported numerical ratings of subjective highness. Post title text was extracted via the Pushshift dataset from N = 328,865 posts to the r/trees Reddit community, where posters self-assess and disclose how high they feel on a scale from 1 to 10 (M = 6.9, SD = 1.8). Structural topic modelling and Linguistic Inquiry and Word Count (LIWC) dictionary-based approaches were applied to identify (1) frequently discussed topics and (2) text indicative of 5 psychological processes (affective, social, cognitive, perceptual, biological), respectively, as well as to examine relationships between subjective highness and (1) topic prevalence and (2) psychological process word counts. A 40-topic model was selected for interpretation based on semantic coherence and exclusivity. The most discussed topics in a 40-topic model were characterized by references to smoking places, social contexts, positive affect, cognitive states, as well as food and media consumed. In LIWC dictionary analyses, words mentioning affective, social, and cognitive processes were referenced more often than perceptual or body processes. Posters reported greater subjective highness when using language that referred to in-person social environments and lower subjective highness when using language that referred to online social environments and positive affect psychological states. This examination of unprompted online reports of naturalistic cannabis use identified textual content referring to affect and to other people as being associated with perceived effects of cannabis. These affective and social aspects of the cannabis use experience were salient to active posters in this online community and should be integrated into experience sampling methods and behavioral pharmacology research, as well as public health messaging.

Model for an Academic Medicine Interest Group: A student-led initiative.

Academic physicians are responsible for the education of medical students, residents, and other practicing physicians through clinical rotations lectures, seminars, research, and conferences. Therefore, the increasing need to recruit academic physicians holds immense value within the healthcare system. Academic Medicine Interest Group (AMIG) is a collective made up of students who share an interest in the growth and advancement of academic medicine. We present a guide and model on establishing an AMIG. We found that AMIG fostered professional growth by providing leadership, research, and teaching opportunities. Strategic planning, effective leadership, and group organization were all necessary for the success of the group.

Stool protein mass spectrometry identifies biomarkers for the early detection of diffuse-type gastric cancer.

There is a high unmet need for early detection approaches for diffuse gastric cancer (DGC). We examined whether the stool proteome of mouse models of GC or individuals with hereditary diffuse GC (HDGC) have utility as biomarkers for early detection. Proteomic mass spectrometry of stool from a genetically engineered mouse model driven by oncogenic KrasG12D and loss of p53 and Cdh1 in gastric parietal cells (known as TCON mice) identified differentially abundant proteins compared to littermate controls. Immunoblot assays validated a panel of proteins including actinin alpha 4 (ACTN4), N-acylsphingosine amidohydrolase 2 (ASAH2), dipeptidyl peptidase 4 (DPP4), and valosin-containing protein (VCP) as enriched in TCON stool compared to littermate control stool. Immunofluorescence analysis of these proteins in TCON stomach sections revealed increased protein expression as compared to littermate controls. Proteomic mass spectrometry of stool obtained from HDGC patients with CDH1 mutations identified increased expression of ASAH2, DPP4, VCP, lactotransferrin (LTF), and tropomyosin-2 (TPM2) relative to stool from healthy sex and age-matched donors. Chemical inhibition of ASAH2 using C6-urea ceramide was toxic to GC cell lines and patient derived-GC organoids. This toxicity was reversed by adding downstream products of the S1P synthesis pathway, suggesting a dependency on ASAH2 activity in GC. An exploratory analysis of the HDGC stool microbiome identified features which correlated with patient tumors. Here we provide evidence supporting the potential of analyzing stool biomarkers for the early detection of DGC.

SIRT7 regulates NUCKS1 chromatin binding to elicit metabolic and inflammatory gene expression in senescence and liver aging.

Sirtuins, a class of highly conserved histone/protein deacetylases, are heavily implicated in senescence and aging. The regulation of sirtuin proteins is tightly controlled both transcriptionally and translationally and via localization within the cell. While Sirtiun proteins are implicated with aging, how their levels are regulated during aging across cell types and eliciting tissue specific age-related cellular changes is unclear. Here, we demonstrate that SIRT7 is targeted for degradation during senescence and liver aging. To uncover the significance of SIRT7 loss, we performed proteomics analysis and identified a new SIRT7 interactor, the HMG box protein NUCKS1. We found that the NUCKS1 transcription factor is recruited onto chromatin during senescence and this is mediated by SIRT7 loss. Further, depletion of NUCKS1 delayed senescence upon DNA damage leading to reduction of inflammatory gene expression. Examination of NUCKS1 transcriptional regulation during senescence revealed gene targets of transcription factors NFKB1, RELA, and CEBPß. Consistently, in both Sirt7 KO mouse liver and in naturally aged livers, Nucks1 was recruited to chromatin. Further, Nucks1 was bound at promoters and enhancers of age-related genes, including transcription factor Rela, and, moreover, these bound sites had increased accessibility during aging. Overall, our results uncover NUCKS1 as a novel interactor of SIRT7, and show that loss of SIRT7 during senescence and liver aging promotes NUCKS1 chromatin binding to regulate metabolic and inflammatory genes.

Native American ancestry and breast cancer risk in Colombian and Mexican women: ruling out potential confounding through ancestry-informative markers.

BACKGROUND: Latin American and Hispanic women are less likely to develop breast cancer (BC) than women of European descent. Observational studies have found an inverse relationship between the individual proportion of Native American ancestry and BC risk. Here, we use ancestry-informative markers to rule out potential confounding of this relationship, estimating the confounder-free effect of Native American ancestry on BC risk. METHODS AND STUDY POPULATION: We used the informativeness for assignment measure to select robust instrumental variables for the individual proportion of Native American ancestry. We then conducted separate Mendelian randomization (MR) analyses based on 1401 Colombian women, most of them from the central Andean regions of Cundinamarca and Huila, and 1366 Mexican women from Mexico City, Monterrey and Veracruz, supplemented by sensitivity and stratified analyses. RESULTS: The proportion of Colombian Native American ancestry showed a putatively causal protective effect on BC risk (inverse variance-weighted odds ratio [OR] = 0.974 per 1% increase in ancestry proportion, 95% confidence interval [CI] 0.970-0.978, p = 3.1 × 10-40). The corresponding OR for Mexican Native American ancestry was 0.988 (95% CI 0.987-0.990, p = 1.4 × 10-44). Stratified analyses revealed a stronger association between Native American ancestry and familial BC (Colombian women: OR = 0.958, 95% CI 0.952-0.964; Mexican women: OR = 0.973, 95% CI 0.969-0.978), and stronger protective effects on oestrogen receptor (ER)-positive BC than on ER-negative and triple-negative BC. CONCLUSIONS: The present results point to an unconfounded protective effect of Native American ancestry on BC risk in both Colombian and Mexican women which appears to be stronger for familial and ER-positive BC. These findings provide a rationale for personalised prevention programmes that take genetic ancestry into account, as well as for future admixture mapping studies.

A Cohort Study Assessing the Impact of Anki as a Spaced Repetition Tool on Academic Performance in Medical School.

Introduction: Anki is an application that capitalizes upon the techniques of spaced repetition and is increasingly utilized by medical students for examination preparation. This study examines the impact of Anki usage in a medical school curriculum on academic performance. Secondary objectives analyzed individual Anki utilization and a qualitative assessment of Anki use. Methods: A cohort-control study was conducted at Boonshoft School of Medicine. One hundred thirty first-year medical students were enrolled in an Anki utilization training program from July 2021 to September 2021. Training included educational Anki courses and subsequent survey data collection over Anki usage. Data variables included all course final examinations, the Comprehensive Basic Science Exam (CBSE), individual Anki user statistics, nationally standardized exams scores, and Qualtrics surveys on student perceived ease of use. Results: Seventy-eight students reported using Anki for at least one of the exams, and 52 students did not use Anki for any exam. Anki users scored significantly higher across all four exams: Course I (6.4%; p < 0.001); Course II (6.2%; p = 0.002); Course III (7.0%; p = 0.002); and CBSE (12.9%; p = 0.003). Students who reported higher dependency on Anki for studying performed significantly better on the Course I, II, and CBSE exams. Conclusion: Anki usage may be associated with an increase in standardized examination scores. This supports Anki as an evidence-based spaced repetition and active retrieval learning modality for medical school standardized examinations. There was little correlation between its specific statistical markers and examination performance. This is pertinent to physicians and medical students alike as the learning and preservation of biomedical knowledge is required for examinations and effective clinical care.

An interlaboratory study to evaluate the utility of gas chromatography-mass spectrometry and gas chromatography-infrared spectroscopy spectral libraries in the forensic analysis of fentanyl-related substances.

Synthetic opioids such as fentanyl account for over 71,000 of the approximately 107,000 overdose deaths reported in the United States in 2021. Fentanyl remains the fourth most identified drug by state and local forensic laboratories, and the second most identified drug by federal laboratories. The unambiguous identification of fentanyl-related substances (FRS) is challenging due to the absence or low abundance of a molecular ion in a typical gas chromatography-mass spectrometry (GC-MS) analysis and due to a low number of fragment ions that are similar among the many potential isomers of FRS. This study describes the utility of a previously reported gas chromatography-infrared (GC-IR) library for the identification of FRS within a blind, interlaboratory study (ILS) involving seven forensic laboratories. Twenty FRS reference materials, including those with isomer pairs in the library, were selected based on either their presence in the NIST library and/or some similarity of the mass spectra information produced. The ILS participants were requested to use the Florida International University (FIU) GC-MS and GC-IR libraries supplied by FIU to search for matches to their unknown spectra generated from in-house GC-MS and GC-IR analysis. The laboratories reported improvement in the positive identification of unknown FRS from ~75% using GC-MS alone to 100% correct identification using GC-IR analysis. One laboratory participant used solid phase IR analysis, which produced spectra incompatible with the vapor phase GC-IR library to generate a good comparison spectrum. However, this improved when searched against a solid phase IR library.

Creation of an Application to Increase Surgical Resident Operative Case Coverage.

PURPOSE: Studies have shown that the confidence of surgical residents to perform procedures after completing residency can be affected by their volume of operative experiences. Many surgical residencies span multiple hospitals with a multitude of attendings providing additional educational opportunities available via cross-coverage. This study aims to evaluate the use of a mobile application (app) for operative cross-coverage to improve surgical opportunities in a large surgical residency program and decrease the number of uncovered cases. METHODS: An app allowing for uncovered cases to be sent to all surgical residents was used starting March 2022. A survey was completed by residents pre- and postapp implementation. A retrospective chart review was conducted of all general surgery procedures at the 2 major hospital systems 4 months before and after implementation to evaluate resident case coverage. RESULTS: In the preapp survey, 71% (27/38) of residents noted cross-covering 1 or more cases a month with 90% (34/38) reporting, they were unaware of all cases available. In the postapp survey, 100% of residents reported better awareness of available cases, 97% (35/36) reported uncovered cases were more easily accessible, 100% felt the app simplified finding coverage, and 100% wanted to continue the app long-term. On retrospective review, 7210 cases were identified in the preapp and postapp period with an increased volume of cases in the postapp period. After implementation of the case coverage app, there was a significant increase in total case coverage (p = <0.001) as well as a significant increase in coverage of endoscopic (p = 0.007), laparoscopic (p = 0.025), open (p = 0.015) and robotic cases (p = <0.001). CONCLUSIONS: This study shows the impact that technological innovation can play in the education and operative experiences of surgical residents. This can be used to improve operative experiences of residents in various surgical fields in any training program throughout the country.

Alternative Abdominal Wall Plication Techniques: A Review of Current Literature.

Abdominoplasty is one of the most common procedures performed in plastic surgery. By removing redundant skin and fat tissue, body contouring narrows the waist and achieves a naturally flattened appearance. To achieve this, one technique frequently utilized is plication of the abdominal rectus sheath. Although abdominal wall plication is commonly performed during abdominoplasty, there is a lack of consensus regarding which plication method provides the best outcomes. Each variation addresses some of the common intraoperative and postoperative complications of abdominoplasty. These include extended operating time, rupture of the plication, epigastric bulging, and patient postoperative dissatisfaction. Many plication techniques have been described in the literature, but no single technique has been adopted by plastic surgeons as the gold standard. Here we present a narrative comparison of current published literature reporting novel or modified abdominoplasty plication techniques. This includes diagrams of each procedure, sutures utilized, and key concepts of each plication technique. Discussion regarding how these modifications change operating time, alter epigastric bulging, and improve the ability to narrow the waist is provided. The purpose of this paper is to provide a concise source document for plastic surgeons to reference when choosing a plication method to use during abdominoplasty.

Monitoring for fentanyl within Australian supervised injecting facilities: Findings from feasibility testing of novel methods and collaborative workshops.

BACKGROUND: Australia is yet to see widespread fentanyl-contaminated heroin, despite the established presence of fentanyl in other countries. International mortality trends alongside a local cluster of fentanyl-related deaths prompted interest in developing methods to monitor for fentanyl and other potentially harmful novel psychoactive substances (NPS) in Australia. METHODS: We tested novel methods to monitor for fentanyl and other NPS. From 2017-2021, clients from supervised injecting facilities (SIFs) in Melbourne and Sydney, Australia, contributed urine screens (UDS) with BTNX Rapid Response™ fentanyl test strips (FTS) paired with surveys, and injecting equipment associated with opioid overdoses for laboratory analysis. A single site piloted drug checking using FTS with laboratory confirmation. Two workshops were conducted with SIF staff, content experts and people with lived experience to determine how results can inform practices within SIFs. RESULTS: Of the 911 UDS with FTS conducted, less than 1% (n=8) yielded positive results that were not explained by self-reported pharmaceutical fentanyl use, with two laboratory confirmed fentanyl positive results. Injecting equipment from 59 overdoses was tested and neither fentanyl nor other NPS were identified. Drug checking with FTS (n=34) indicated the presence of fentanyl on three tests. Two specimens were subsequently sent for laboratory testing and classified as false positives as the presence of fentanyl was not confirmed. Workshop participants (n=21) felt routine monitoring with FTS currently had limited value. A process for using pre-defined signals to trigger surveillance was developed. CONCLUSION: The high false positive rates with FTS, relative to the small number of positive results and potential for them to undermine confidence in FTS emphasised the need for confirmatory testing. The role of routine surveillance was unclear within the current low-fentanyl context, however, a process was developed to upscale testing should signals of increased fentanyl prevalence in the Australian heroin market emerge.

The role of sirtuins in dermal fibroblast function.

The sirtuins are a family of seven proteins that perform a variety of dermatological functions and help maintain both the structure and function of the skin. More specifically, the sirtuins have been shown to be altered in multiple dermal cell types including dermal fibroblasts. The functions of dermal fibroblasts are extensive, and include playing a significant role in wound healing as well as helping to maintain the integrity of the skin. As dermal fibroblasts age, they can undergo a state of permanent cell cycle arrest, known as cellular senescence. This senescent process can occur as a result of various stressors, including oxidative stress, ultraviolet radiation -induced stress, and replicative stress. In recent years, there has been a growing interest in both enhancing the cutaneous fibroblast's ability to facilitate wound healing and altering fibroblast cellular senescence. Thus, in this review, we examine the relationship between sirtuin signaling and dermal fibroblasts to understand how this family of proteins may modulate skin conditions ranging from the wound healing process to photocarcinogenesis associated with fibroblast senescence. Additionally, we offer supporting data from experiments examining the relationship between fibroblast senescence and sirtuin levels in an oxidative stress model indicating that senescent dermal fibroblasts exhibit diminished sirtuin levels. Furthermore, we survey the research on the role of sirtuins in specific dermatological disease states that where dermal fibroblast function has been implicated. Finally, we conclude with outlining potential clinical applications of sirtuins in dermatology. In sum, we find that the literature on the involvement of sirtuins in dermal fibroblasts is limited, with research still in its early stages. Nevertheless, intriguing preliminary findings merit additional investigation into the clinical implications of sirtuins in dermatology.

Cerebral Venous Sinus Thrombosis Following an mRNA COVID-19 Vaccination and Recent Oral Contraceptive Use.

Rising concerns of cerebral venous sinus thrombosis (CVST) and other forms of venous thromboembolism have been associated with the SARS-CoV-2 vaccinations. Adverse effects with vector-based vaccines are well documented in the literature, while less is known about the mRNA vaccines. This report documents a case of CVST in a 32-year-old female patient who received her second Pfizer mRNA COVID-19 vaccination 16 days prior to hospital admission and had started oral combined contraceptives approximately 4 months beforehand. Clinicians should be cognizant of the possibility that mRNA vaccines, when combined with other risk factors like oral contraceptive pill use, may enhance one's hypercoagulable status.

Prescription medication use and trends for U.S. Navy submariners from 2007 to 2018.

Introduction: This is the first study to examine population medication prescription rates among U.S. submariners by common therapeutic classifications. Methods: Individual-level pharmacy records during the years 2007 to 2018 were extracted from the Military Health System's Pharmacy Data Transaction Service (PDTS) file. Demographic and military factors captured from Navy personnel files were linked to PDTS records. Logistic regression models were used to identify characteristics and trends associated with prevalence. Published total rates for other active-duty components were compared to submariner rates. Results: There were data for 50,720 submariners, among whom 576,782 prescriptions were filled. Prevalence rates decreased significantly from 2007-2018 among most drug classes. Central nervous system agents accounted for 31% of the total prescriptions, followed by 12% for eye, ear, nose, and throat preparations, and 10% for anti-infective agents. Higher prescription rates were associated with being enlisted, younger, a woman, lower-ranked, or Hispanic. The mean yearly prescription rate was 2.7 per submariner, less than half of the overall rate of all military components. Conclusion: The survival benefit of HBO2 therapy observed in our unadjusted analysis suggests that there may be therapeutic benefits of HBO2 in treating COVID-19 hypoxia as an adjunct to standard care.

A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A.

Sirtuin 6 (SIRT6) is a deacylase and mono-ADP ribosyl transferase (mADPr) enzyme involved in multiple cellular pathways implicated in aging and metabolism regulation. Targeted sequencing of SIRT6 locus in a population of 450 Ashkenazi Jewish (AJ) centenarians and 550 AJ individuals without a family history of exceptional longevity identified enrichment of a SIRT6 allele containing two linked substitutions (N308K/A313S) in centenarians compared with AJ control individuals. Characterization of this SIRT6 allele (centSIRT6) demonstrated it to be a stronger suppressor of LINE1 retrotransposons, confer enhanced stimulation of DNA double-strand break repair, and more robustly kill cancer cells compared with wild-type SIRT6. Surprisingly, centSIRT6 displayed weaker deacetylase activity, but stronger mADPr activity, over a range of NAD+ concentrations and substrates. Additionally, centSIRT6 displayed a stronger interaction with Lamin A/C (LMNA), which was correlated with enhanced ribosylation of LMNA. Our results suggest that enhanced SIRT6 function contributes to human longevity by improving genome maintenance via increased mADPr activity and enhanced interaction with LMNA.

UVB-Induced Microvesicle Particle Release and Its Effects on the Cutaneous Microenvironment.

Ultraviolet B radiation (UVB) has profound effects on human skin that results in a broad spectrum of immunological local and systemic responses and is the major cause of skin carcinogenesis. One important area of study in photobiology is how UVB is translated into effector signals. As the skin is exposed to UVB light, subcellular microvesicle particles (MVP), a subtype of bioactive extracellular vesicles, are released causing a variety of local and systemic immunological effects. In this review, we highlight keratinocyte MVP release in keratinocytes in response to UVB. Specifically, Platelet-activating factor receptor agonists generated by UVB result in MVP released from keratinocytes. The downstream effects of MVP release include the ability of these subcellular particles to transport agents including the glycerophosphocholine-derived lipid mediator Platelet-activating factor (PAF). Moreover, even though UVB is only absorbed in the epidermis, it appears that PAF release from MVPs also mediates systemic immunosuppression and enhances tumor growth and metastasis. Tumor cells expressing PAF receptors can use this mechanism to evade chemotherapy responses, leading to treatment resistance for advanced cancers such as melanoma. Furthermore, novel pharmacological agents provide greater insight into the UVB-induced immune response pathway and a potential target for pharmacological intervention. This review outlines the need to more clearly elucidate the mechanism linking UVB-irradiation with the cutaneous immune response and its pathological manifestations. An improved understanding of this process can result in new insights and treatment strategies for UVB-related disorders from carcinogenesis to photosensitivity.

In-Situ Bromination Enables Formal Cross-Electrophile Coupling of Alcohols with Aryl and Alkenyl Halides.

Although alcohols are one of the largest pools of alkyl substrates, approaches to utilize them in cross-coupling and cross-electrophile coupling are limited. We report the use of 1° and 2° alcohols in cross-electrophile coupling with aryl and vinyl halides to form C(sp3)-C(sp2) bonds in a one-pot strategy utilizing a very fast (<1 min) bromination. The reaction's simple benchtop setup and broad scope (42 examples, 56% ± 15% ave yield) facilitates use at all scales. The potential in parallel synthesis applications was demonstrated by successfully coupling all combinations of 8 alcohols with 12 aryl cores in a 96-well plate.

Explicating How Skill Determines the Qualities of User-Avatar Bonds.

Many frameworks exist that explain how people interact with avatars. Our core argument is that the primary theoretical mechanisms of a user-avatar bond (i.e., UAB) rest with the way people engage avatars and, thereby, the broader digital environment. To understand and predict such engagement, we identify a person's skill in handling/engaging the avatar in the digital environment as an ordering parameter (i.e., organizing predictor). Accordingly, we define skill as a person's ability to enact their agency successfully to achieve desired states. To explain how skill orders experience, we ground our theorizing in ecological perception and systems theory. In our explication, we describe how stable action coupling (i.e., the linking of action inputs to perceived outcomes) enables a state of embeddedness (i.e., when the environment facilitates and constrains behaviors) in the digital environment. Then, we explain how embeddedness promotes motivational attunement (i.e., orienting of motivational systems) and what the digital environment affords to users at different levels of skill. Throughout, we consider how our theoretical scaffolding generates tractable contentions regarding how skill influences UABs.

Health Conditions Among Navy Submariners at the End of Active Duty; A Retrospective Cohort Study.

INTRODUCTION: Maintaining healthy, well-trained, and highly qualified armed forces is critical for ensuring military readiness. The purpose of this article is to contribute to the body of research focused on the health of U.S. Navy submariners and to identify the health conditions of U.S. Navy submariners during their final year of active duty service. MATERIALS AND METHODS: In this retrospective cohort study, we examined medical records and personnel files of separating U.S. Navy sailors who were: (1) active duty between 2009 and 2018; (2) separated before 2019; and (3) were assigned to a submarine for at least 30 days. Both officers and enlisted service members were included. We linked, described, and analyzed data from the Defense Health Agency, Military Health System Data Repository (MDR), and the Bureau of Naval Personnel (BUPERS). International Classification of Diseases (ICD) diagnoses codes were obtained from MDR. Data collected from BUPERS include age, sex, and rank. We determined the number of individuals who had at least one diagnosed condition (identified as a three-digit ICD code). We report the number of diagnoses and calculate prevalence rates and confidence intervals per condition, as well as prevalence rates per year, using standard formulas. The study was approved by the Naval Submarine Medical Research Laboratory Institutional Review Board. RESULTS: During the study period, 26,014 submariners separated from the Navy. The average number of separations per year was 2,601. About a third of the separating submariners were in the 25 to 29 age group and over 50% were under 30 years of age. Of the three-digit individual ICD codes, some of the highest operationally relevant rates over the 10-year study period (2009-2018) were for joint disorders (prevalence rate [PR] = 180 per 1,000 submariners), back disorders (PR = 128), and sleep disorders (PR = 134). Three mental-health-related conditions were also among the 20 conditions with the highest rates. CONCLUSIONS: High rates of specific diagnoses such as joint disorders indicate the need for additional study to examine causal relationships, to determine which conditions may contribute to lost work time, early separations, or low rates of reenlistment and which conditions might be a result of specific military occupations or duties. Study strengths are the large number of subjects and the long period of observations. A study weakness was the inability to identify submariners who separated because of health conditions. The overall impact of the study is that it identifies urgent health risks and establishes a way to prioritize future research. Future research should include a focus on medically separated personnel; compare rates for submariners to other military groups including all-Navy and all-Department of Defense; and determine specific and relative risks as a necessary precursor to developing, implementing, and testing risk reduction and health improvement interventions.