Is the 21st birthday a turning point for alcohol and cannabis use? A monthly study of young adults.

BACKGROUND: An important life-course event with respect to alcohol and cannabis use is turning 21 years of age, which may be associated with increases in use of these substances due to celebrations during the month and easier access to them on and following this birthday. We examined the trajectories of alcohol and cannabis use behaviors in the months leading up to, during, and following the 21st birthday month. We also examined whether the use trajectories vary by college status and baseline levels of use. METHODS: We used data from 203 young adults recruited from the Greater Seattle region who turned 21 during the course of the study. Surveys were administered each month for 24 consecutive months. Measures included the typical number of drinks per week for the past month, the frequency of heavy episodic drinking, the number of cannabis use days, and any simultaneous alcohol and cannabis use. Multilevel spline models were run that estimated linear slopes over time at four intervals: (1) up to 1 month before the 21st birthday month; (2) from 1 month before to the month of the 21st birthday; (3) from the 21st birthday month to 1 month following; and (4) from 1 month following the 21st birthday month through all following months. RESULTS: Alcohol use, generally, and simultaneous alcohol and cannabis use showed sharp increases from the month before the 21st birthday month to the 21st birthday month and decreases following the 21st birthday month. For cannabis use, there were significant increases in the months leading up to the 21st birthday and no other significant changes during other time intervals. Patterns differed by baseline substance use and college status. CONCLUSIONS: Findings from the current study have implications for the timing and personalization of prevention and intervention efforts. Event-specific 21st birthday interventions may benefit from incorporating content targeting specific hazardous drinking behaviors in the month prior to the 21st birthday.

Long-Term Ultrasound Twinkling Detectability and Safety of a Polymethyl Methacrylate Soft Tissue Marker Compared to Conventional Breast Biopsy Markers-A Preclinical Study in a Porcine Model.

OBJECTIVE: We have studied the use of polymethyl methacrylate (PMMA) as an alternative biopsy marker that is readily detectable with ultrasound Doppler twinkling in cases of in vitro, ex vivo, or limited duration in vivo settings. This study investigates the long-term safety and ultrasound Doppler twinkling detectability of a PMMA breast biopsy marker following local perturbations and different dwell times in a 6-mo animal experiment. METHODS: This study, which was approved by our Institutional Animal Care and Use Committee, involved three pigs and utilized various markers, including PMMA (Zimmer Biomet), 3D-printed, and Tumark Q markers. Markers were implanted at different times for each pig. Mesh material or ethanol was used to induce a local inflammatory reaction near certain markers. A semiquantitative twinkling score assessed twinkling for actionable localization during monthly ultrasounds. At the primary endpoint, ultrasound-guided localization of lymph nodes with detectable markers was performed. Following surgical resection of the localized nodes, histomorphometric analysis was conducted to evaluate for tissue ingrowth and the formation of a tissue rind around the markers. RESULTS: No adverse events occurred. Twinkling scores of all markers for all three pigs decreased gradually over time. The Q marker exhibited the highest mean twinkling score followed by the PMMA marker, PMMA with mesh, and Q with ethanol. The 3D-printed marker with mesh and PMMA with ethanol had the lowest scores. All wire-localized lymph nodes were successfully resected. Despite varying percentages of tissue rind around the markers and a significant reduction in overall twinkling (p < 0.001) over time, mean PMMA twinkling scores remained clinically actionable at 6 and 5 mo using a General Electric C1-6 probe and 9L-probe, respectively. CONCLUSIONS: In this porcine model, the PMMA marker demonstrates an acceptable safety profile. Clinically actionable twinkling aids PMMA marker detection even after 6 mo of dwell time in porcine lymph nodes. The Q marker maintained the greatest twinkling over time compared to all the other markers studied.

Color VISION for improved ultrasound visualization of brachytherapy needles.

BACKGROUND: High dose rate brachytherapy is commonly used in the treatment of prostate cancer. Treatment planning is often performed under transrectal ultrasound (US) guidance, but brachytherapy needles can be challenging to digitize due to the presence of poor US conspicuity and imaging artifacts. The plan accuracy and quality, however, are dependent on the proper visualization of the needles with millimeter accuracy. PURPOSE: This work describes a technique for generating a color overlay of needle locations atop the grayscale US image. Prototype devices were developed to produce vibrations in the brachytherapy needles that generate a high contrast color Doppler (CD) signal that highlights the needle locations with superior contrast and reduced artifacts. Denoted by the acronym color VISION (Vibrationally Induced Shimmering for Identifying an Object's Nature), the technology has the potential to improve applicator conspicuity and facilitate automated applicator digitization. METHODS: Three prototype vibrational devices with frequencies between 200-450 Hz were designed in-house and evaluated with needle implants in a phantom and cadaveric male pelvis using: (1) an actuator attached to the front of a prostate needle template; (2) an actuator attached to the top of the needle template; and (3) a hand-held actuator with a stylet, inserted directly into a needle's inner lumen. Acquired images were postprocessed in MATLAB to evaluate the potential for automated digitization. RESULTS: All prototype devices produced localized shimmering in implanted brachytherapy needles in both the axial and sagittal planes. The template mounted actuators provided better vibrational coupling and ease of operation than the stylet prototype. The Michelson contrast, or visibility, of the shimmering CD signal was 100% compared with ≤40% for B-mode imaging of a single needle. Proof-of-principle for automated applicator digitization using only the CD signal was demonstrated. CONCLUSIONS: The color VISION prototype devices successfully coupled mechanical vibrations into brachytherapy needles to generate US CD shimmering and accurately highlight brachytherapy needle locations. The high contrast and natively registered signal are promising for future work to automate the needle digitization and provide a real-time visual overlay of the applicator on the B-mode US image.

Mutant IDH inhibitors induce lineage differentiation in IDH-mutant oligodendroglioma.

A subset of patients with IDH-mutant glioma respond to inhibitors of mutant IDH (IDHi), yet the molecular underpinnings of such responses are not understood. Here, we profiled by single-cell or single-nucleus RNA-sequencing three IDH-mutant oligodendrogliomas from patients who derived clinical benefit from IDHi. Importantly, the tissues were sampled on-drug, four weeks from treatment initiation. We further integrate our findings with analysis of single-cell and bulk transcriptomes from independent cohorts and experimental models. We find that IDHi treatment induces a robust differentiation toward the astrocytic lineage, accompanied by a depletion of stem-like cells and a reduction of cell proliferation. Furthermore, mutations in NOTCH1 are associated with decreased astrocytic differentiation and may limit the response to IDHi. Our study highlights the differentiating potential of IDHi on the cellular hierarchies that drive oligodendrogliomas and suggests a genetic modifier that may improve patient stratification.

A Radiological Clip Design Using Ultrasound Identification to Improve Localization.

OBJECTIVE: We demonstrate the use of ultrasound to receive an acoustic signal transmitted from a radiological clip designed from a custom circuit. This signal encodes an identification number and is localized and identified wirelessly by the ultrasound imaging system. METHODS: We designed and constructed the test platform with a Teensy 4.0 microcontroller core to detect ultrasonic imaging pulses received by a transducer embedded in a phantom, which acted as the radiological clip. Ultrasound identification (USID) signals were generated and transmitted as a result. The phantom and clip were imaged using an ultrasonic array (Philips L7-4) connected to a Verasonics™ Vantage 128 system operating in pulse inversion (PI) mode. Cross-correlations were performed to localize and identify the code sequences in the PI images. RESULTS: USID signals were detected and visualized on B-mode images of the phantoms with up to sub-millimeter localization accuracy. The average detection rate across 30,400 frames of ultrasound data was 98.1%. CONCLUSION: The USID clip produced identifiable, distinguishable, and localizable signals when imaged. SIGNIFICANCE: Radiological clips are used to mark breast cancer being treated by neoadjuvant chemotherapy (NAC) via implant in or near treated lesions. As NAC progresses, available marking clips can lose visibility in ultrasound, the imaging modality of choice for monitoring NAC-treated lesions. By transmitting an active signal, more accurate and reliable ultrasound localization of these clips could be achieved and multiple clips with different ID values could be imaged in the same field of view.

Short-term changes in social role statuses across young adulthood and their relation to heavy drinking in a given month.

Young adulthood is a developmental period during which individuals experience shifts in their social roles in various domains, which coincides with a period of time that is also high risk for lifetime peaks in alcohol use. The current study examined age-related changes in heavy episodic drinking (HED) and high-intensity drinking (HID) and associations with short-term (i.e., monthly) variation in young adults' social roles over a 2.5-year period in a community sample of young adults who reported past-year alcohol use (N = 778, baseline age range 18-23). Results showed probabilities of past-month HED and HID changed in a nonlinear fashion across ages 18-26 with greater probabilities of use at younger ages. Most participants did not report being in the same social role status every sampled month, underscoring the presence of short-term role variation. Living with parents and being in a serious romantic relationship in a given month were negatively associated with past-month HED. Living with parents in a given month was also negatively associated with past-month HID. Being a 4-year college student and being employed full-time in a given month were not significantly related to either outcome. Findings provided partial evidence that monthly statuses were associated with heavy drinking. Several avenues for future research are described in light of the findings.

Proposing a framework to quantify the potential impact of pharmacokinetic drug-drug interactions caused by a new drug candidate by using real world data about the target patient population.

Drug development teams must evaluate the risk/benefit profile of new drug candidates that perpetrate drug-drug interactions (DDIs). Real-world data (RWD) can inform this decision. The purpose of this study was to develop a predicted impact score for DDIs perpetrated by three hypothetical drug candidates via CYP3A, CYP2D6, or CYP2C9 in type 2 diabetes mellitus (T2DM), obesity, or migraine. Optum Market Clarity was analyzed to estimate use of CYP3A, CYP2D6, or CYP2C9 substrates classified in the University of Washington Drug Interaction Database as moderate sensitive, sensitive, narrow therapeutic index, or QT prolongation. Scoring was based on prevalence of exposure to victim substrates and characteristics (age, polypharmacy, duration of exposure, and number of prescribers) of those exposed. The study population of 14,163,271 adults included 1,579,054 with T2DM, 3,117,753 with obesity, and 410,436 with migraine. For T2DM, 71.3% used CYP3A substrates, 44.3% used CYP2D6 substrates, and 44.3% used CYP2C9 substrates. For obesity, 57.1% used CYP3A substrates, 34.6% used CYP2D6 substrates, and 31.0% used CYP2C9 substrates. For migraine, 64.1% used CYP3A substrates, 44.0% used CYP2D6 substrates, and 28.9% used CYP2C9 substrates. In our analyses, the predicted DDI impact scores were highest for DDIs involving CYP3A, followed by CYP2D6, and CYP2C9 substrates, and highest for T2DM, followed by migraine, and obesity. Insights from RWD can be used to estimate a predicted DDI impact score for pharmacokinetic DDIs perpetrated by new drug candidates currently in development. This score can inform the risk/benefit profile of new drug candidates in a target patient population.

DNA Reference Reagents for Genotyping RH Variants.

Patients who carry Rhesus (RH) blood group variants may develop Rh alloantibodies requiring matched red blood cell transfusions. Serologic reagents for Rh variants often fail to specifically identify variant Rh antigens and are in limited supply. Therefore, red blood cell genotyping assays are essential for managing transfusions in patients with clinically relevant Rh variants. Well-characterized DNA reference reagents are needed to ensure quality and accuracy of the molecular tests. Eight lyophilized DNA reference reagents, representing 21 polymorphisms in RHD and RHCE, were produced from an existing repository of immortalized B-lymphoblastoid cell lines at the Center for Biologics Evaluation and Research/US Food and Drug Administration. The material was validated through an international collaborative study involving 17 laboratories that evaluated each DNA candidate using molecular assays to characterize RHD and RHCE alleles, including commercial platforms and laboratory-developed testing, such as Sanger sequencing, next-generation sequencing, and third-generation sequencing. The genotyping results showed 99.4% agreement with the expected results for the target RH polymorphisms and 87.9% for RH allele agreement. Most of the discordant RH alleles results were explained by a limited polymorphism coverage in some genotyping methods. Results of stability and accelerated degradation studies support the suitability of these reagents for use as reference standards. The collaborative study results demonstrate the qualification of these eight DNA reagents for use as reference standards for RH blood group genotyping assay development and analytical validation.

An Expanded Daily Alcohol Expectancies Measure: Results on the Multilevel Factor Structure and Psychometric Properties.

OBJECTIVE: Alcohol expectancies are beliefs people have about the likelihood of experiencing various positive or negative consequences related to alcohol use. Expectancies have most commonly been treated as trait-like characteristics of individuals, but some researchers have assessed expectancies as state-level characteristics that vary within-persons across days. Previous work developed a 13-item daily alcohol expectancies measure. This study evaluated an expanded version of that measure that includes 10 additional expectancy items. METHOD: Participants were 2- and 4-year college students (N=201; 63.7% female; 55.2% White Non-Hispanic; 75.1% 4-year students) randomized to the control group of a longitudinal study designed to test the efficacy of a just-in-time adaptive intervention delivered via mobile app to reduce high-risk alcohol use. Multilevel exploratory factor analysis was used to determine the factor structure at the daily and person levels. Multilevel models were used to evaluate the convergent validity of the resulting subscales. RESULTS: Two factors, broadly representing positive and negative alcohol expectancies, were retained at the daily and person levels. Composite reliability (ω) estimates ranged from 0.85 to 0.96 and suggested that the reliability of the resulting subscales was good to strong. Associations between the daily expectancy subscales and baseline scores on an established expectancies measure provided preliminary evidence of convergent validity. CONCLUSIONS: Findings indicate that this expanded 23-item daily alcohol expectancies measure is psychometrically sound. This measure is appropriate for use in daily or just-in-time expectancy challenge interventions and is suitable for use among 2- and 4-year college students who drink alcohol regularly and occasionally in heavy quantities and who experience alcohol-related negative consequences.

A daily-level examination of willingness to pregame, blackout, and hook up across drinking days: Associations with respective behavioral outcomes among adolescents and young adults.

Research indicates general willingness to drink (i.e., "How willing are you to drink tonight?") fluctuates day-to-day and is associated with daily-level drinking. However, it is unknown whether willingness to engage in specific alcohol-related behaviors is associated with actual engagement in those behaviors above and beyond general willingness to drink at the daily level. The present study examined whether daily-level willingness to engage in specific behaviors (i.e., pre-gaming, blacking out, hooking up) predicted engaging in those respective behaviors on drinking days above and beyond one's general willingness to drink. Participants included adolescents and young adults who were part of a longitudinal ecological momentary assessment (EMA) study on cognitions and alcohol use. Participants (N = 675; 43 % male) who reported drinking on weekend days (i.e., Friday and Saturday [N = 3,727 days]), were included. The study involved a 3-week EMA burst design with bursts occurring quarterly over 12 months. Multilevel logistic regressions indicated on drinking days when participants reported being more willing than their own average to pre-game (OR = 1.77, p <.001), black out (OR = 1.46, p <.05), or drink before hooking up (OR = 1.68, p <.001), they were more likely to pregame, black out, and hook up, respectively, whereas general willingness to drink was not associated with any outcomes at the daily level.Results suggest willingness to engage in specific behaviors may be essential to target in prevention programming in comparison to general willingness to drink when aiming to reduce specific risk behaviors.

Endoscopic endonasal approach for olfactory groove meningioma resection: Strategies and outcomes in a retrospective case series.

OBJECTIVE: Though the endoscopic endonasal approach (EEA) is a widely accepted treatment for skull base tumors, the specific use of EEA for olfactory groove meningiomas (OGMs) is debated, with variable outcomes reported in the literature. We review the surgical results of OGM resections for one surgeon including the operative approach, surgical nuances, and outcomes, with a focus on factors relating to patient selection which favor EEA over transcranial approaches. METHODS: We retrospectively reviewed thirteen cases of endoscopic endonasal resection of olfactory groove meningiomas. Patient characteristics, clinical characteristics, surgical outcomes, and complications were analyzed. Extent of resection was determined based on volumetric analysis of pre- and postoperative MRI. RESULTS: Anatomic characteristics that render a tumor difficult to access fully are lateral extension beyond the mid-orbit and anterior extension to the falx. Simpson Grade I resection was achieved in 11/13 (84.6 %) cases. Mean pre-operative tumor volume was 8.99 cm3 (range 2.19-16.79 cm3), and 92 % of tumors were WHO grade I. We demonstrate 2 cases of smell preservation, possible with small unilateral tumors and tumors that are confined to either the anterior or posterior portion of the cribriform plate. The post-operative CSF leak rate was 7.7 %, without prophylactic lumbar CSF drainage. The mortality rate was 7.7 % (n = 1) after infectious complications following CSF leak. CONCLUSIONS: Endoscopic endonasal resection of olfactory groove meningiomas is an effective and safe operative method with outcomes and complication rates comparable to transcranial approaches. Key considerations include careful patient selection and familiarity with technical nuances of endoscopic endonasal approach for this specific tumor type.

Oral vancomycin is associated with improved inflammatory bowel disease clinical outcomes in primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD): A matched analysis from the Paediatric PSC Consortium.

BACKGROUND: Data on oral vancomycin for primary sclerosing cholangitis (PSC)-associated inflammatory bowel disease (IBD) are limited. AIMS: Using data from the Paediatric PSC Consortium, to examine the effect of vancomycin on IBD activity. METHODS: In this retrospective multi-centre cohort study, we matched vancomycin-treated and untreated patients (1:3) based on IBD duration at the time of primary outcome assessment. The primary outcome was Physician Global Assessment (PGA) of IBD clinical activity after 1 year (±6 months) of vancomycin. We used generalised estimating equations (GEE) to examine the association between vancomycin and PGA remission, adjusting for IBD type, severity and medication exposures. Secondary outcomes included serum labs and endoscopic remission (global rating of no activity) among those with available data and also analysed with GEE. RESULTS: 113 PSC-IBD patients received vancomycin (median age 12.7 years, 63% male). The matched cohort included 70 vancomycin-treated and 210 untreated patients. Vancomycin was associated with greater odds of IBD clinical remission (odds ratio [OR] 3.52, 95% CI 1.97-6.31; adjusted OR [aOR] 5.24, 95% CI 2.68-10.22). Benefit was maintained in sensitivity analyses restricted to non-transplanted patients and those with baseline moderate-severe PGA. Vancomycin was associated with increased odds of endoscopic remission (aOR 2.76, 95% CI 1.002-7.62; N = 101 with data), and with lower CRP (p = 0.03) and higher haemoglobin and albumin (both p < 0.01). CONCLUSION: Vancomycin was associated with greater odds of IBD clinical and endoscopic remission. Additional, preferably randomised, controlled studies are needed to characterise efficacy using objective markers of mucosal inflammation, and to examine safety and define optimal dosing.

A text message intervention aimed at nurturing peer outreach to help meet drinking limit goals: A remote pilot randomized trial in non-collegiate young adults.

OBJECTIVE: Scalable interventions attempting to nurture peer outreach to help young adults meet drinking limit goals remain under-developed. To address this gap, we developed ASPIRE, a text message intervention focused on coaching individuals to engage with close peers to assist them in meeting drinking limit goals. METHOD: Non-collegiate young adults who had reported one or more heavy drinking days in the preceding month and were at least contemplating change were recruited through social media. Participants were randomly assigned to one of three 6-week text message interventions: Control, Goal Support, or ASPIRE. All groups completed baseline assessments and received weekly text message assessments on Thursdays and Sundays. Control and ASPIRE groups were prompted to complete web-based outcome assessments at 6- and 12-weeks. RESULTS: We enrolled 92 young adults from 31 US states (65% female; 73% White). All groups had high text response rates but intervention usability was sub-optimal. Follow-up rates were 87% at 6-weeks and 79% at 12-weeks. Compared to Control, ASPIRE participants reported significantly more peer support and less peer pressure to drink. ASPIRE exhibited higher goal confidence compared to the Goal Support group. Using multiple imputation, there were no significant differences in drinking outcomes between groups. CONCLUSIONS: Preliminary findings from this pilot study suggest that a text message intervention focused on nurturing peer outreach to help meet drinking limit goals holds promise in altering peer support and pressure as well as boosting drinking limit goal confidence. Design improvements are needed to reduce alcohol consumption.

Prevalence of Distal Symmetrical Polyneuropathy by Diabetes Prevention Program Treatment Group, Diabetes Status, Duration of Diabetes, and Cumulative Glycemic Exposure.

OBJECTIVE: To assess associations between distal symmetric polyneuropathy (DSPN) and Diabetes Prevention Program (DPP) treatment groups, diabetes status or duration, and cumulative glycemic exposure approximately 21 years after DPP randomization. RESEARCH DESIGN AND METHODS: In the DPP, 3,234 adults ≥25 years old at high risk for diabetes were randomized to an intensive lifestyle (ILS), metformin, or placebo intervention to prevent diabetes. After the DPP ended, 2,779 joined the Diabetes Prevention Program Outcomes Study (DPPOS). Open-label metformin was continued, placebo was discontinued, ILS was provided in the form of semiannual group-based classes, and all participants were offered quarterly lifestyle classes. Symptoms and signs of DSPN were assessed in 1,792 participants at DPPOS year 17. Multivariable logistic regression models were used to evaluate DSPN associations with treatment group, diabetes status/duration, and cumulative glycemic exposure. RESULTS: At 21 years after DPP randomization, 66% of subjects had diabetes. DSPN prevalence did not differ by initial DPP treatment assignment (ILS 21.5%, metformin 21.5%, and placebo 21.9%). There was a significant interaction between treatment assignment to ILS and age (P < 0.05) on DSPN. At DPPOS year 17, the odds ratio for DSPN in comparison with ILS with placebo was 17.4% (95% CI 3.0, 29.3) lower with increasing 5-year age intervals. DSPN prevalence was slightly lower for those at risk for diabetes (19.6%) versus those with diabetes (22.7%) and was associated with longer diabetes duration and time-weighted HbA1c (P values <0.001). CONCLUSIONS: The likelihood of DSPN was similar across DPP treatment groups but higher for those with diabetes, longer diabetes duration, and higher cumulative glycemic exposure. ILS may have long-term benefits on DSPN for older adults.

Satellite Remote Sensing: A Tool to Support Harmful Algal Bloom Monitoring and Recreational Health Advisories in a California Reservoir.

Cyanobacterial harmful algal blooms (cyanoHABs) can harm people, animals, and affect consumptive and recreational use of inland waters. Monitoring cyanoHABs is often limited. However, chlorophyll-a (chl-a) is a common water quality metric and has been shown to have a relationship with cyanobacteria. The World Health Organization (WHO) recently updated their previous 1999 cyanoHAB guidance values (GVs) to be more practical by basing the GVs on chl-a concentration rather than cyanobacterial counts. This creates an opportunity for widespread cyanoHAB monitoring based on chl-a proxies, with satellite remote sensing (SRS) being a potentially powerful tool. We used Sentinel-2 (S2) and Sentinel-3 (S3) to map chl-a and cyanobacteria, respectively, classified chl-a values according to WHO GVs, and then compared them to cyanotoxin advisories issued by the California Department of Water Resources (DWR) at San Luis Reservoir, key infrastructure in California's water system. We found reasonably high rates of total agreement between advisories by DWR and SRS, however rates of agreement varied for S2 based on algorithm. Total agreement was 83% for S3, and 52%-79% for S2. False positive and false negative rates for S3 were 12% and 23%, respectively. S2 had 12%-80% false positive rate and 0%-38% false negative rate, depending on algorithm. Using SRS-based chl-a GVs as an early indicator for possible exposure advisories and as a trigger for in situ sampling may be effective to improve public health warnings. Implementing SRS for cyanoHAB monitoring could fill temporal data gaps and provide greater spatial information not available from in situ measurements alone.

Using 3-D-Printed Structures to Evaluate the Potential Causes of the Color Doppler Twinkling Signature.

OBJECTIVE: The color Doppler twinkling artifact has been attributed to existing microbubbles or cavitation occurring on rough objects such as kidney stones, some breast biopsy clips, catheter guidewires and sandpaper. The objective was to investigate the correlation between the surface characteristics of helical constructs with different groove geometries and the occurrence of twinkling, as well as to identify locations conducive to bubble retention and/or cavitation. METHODS: Six half-cylinders were created with a microscale 3-D printer with 5 µm resolution to replicate the geometry of twinkling helical constructs resembling catheter guidewires. Four copies of each marker including a non-twinkling control were printed. The half-cylinders had pitch (peak-to-peak distance) values ranging from 87.5 to 343 µm and amplitude (groove depth) values ranging from 41.5 to 209 µm. The half-cylinders were submerged in degassed water and optically imaged before and after ultrasound insonification to visualize bubbles on the cylinders. The cylinders remained submerged while scanning with the color Doppler mode at frequencies from 3.1 to 6.3 MHz using a GE Logiq E9 scanner and 9L linear array transducer. RESULTS: Two markers exhibited twinkling: one with pitch-to-amplitude ratio of 174/210 µm/µm (0.8) that twinkled only with pre-existing bubbles on the marker; the other had a ratio of 87/87 µm/µm (1.00) that twinkled without pre-existing bubbles on the marker. CONCLUSION: This work provides strong evidence that both existing bubbles and either cavitation or ultrasound wave interactions with patterned or rough surfaces are significant factors in producing the twinkling signature.

Morning cannabis use in young adults: Associations with overall levels of use, negative consequences, and cannabis use disorder symptoms across 2.5 years.

BACKGROUND: Emerging research suggests morning cannabis use may be associated with using more cannabis and experiencing more cannabis-related consequences. This paper examined whether months when young adults reported morning cannabis use (use between 6:00AM and 12:00PM) were associated with cannabis use frequency, negative cannabis-related consequences, and changes in cannabis use disorder (CUD) symptoms. METHODS: Participants were 778 young adults (Mage=21.11 years, 58.5% female) enrolled in a longitudinal study on substance use and social role transitions. Eligible participants were 18-23 years old at screening and reported past-year alcohol use. Participants completed a baseline survey, 24 consecutive monthly surveys, and a follow-up survey 30 months after baseline. Aims were tested using multilevel models and multiple regression. RESULTS: Analyses were limited to cannabis use months (N=4719; 28.9% of sampled months) and participants who reported cannabis use at least once (N=542; 69.7% of all participants). Morning use was reported in 12.3% of cannabis use months and at least once by 23.6% of participants who reported using cannabis. Relative to non-morning use months, morning use months were associated with greater cannabis use frequency and more negative consequences. However, the association between morning use and negative consequences was not statistically significant after controlling for cannabis use frequency. The percentage of cannabis use months with morning use was positively associated with increased CUD symptoms at the 30-month follow-up, relative to baseline. CONCLUSIONS: Morning cannabis use may be a useful marker of high-risk cannabis use and may contribute to the maintenance and worsening of CUD over time.

Idiopathic Granulomatous Mastitis.

Idiopathic granulomatous mastitis (IGM) is a rare, benign inflammatory disorder of the breast that is often underrecognized. The exact etiology and pathophysiology are unknown, but milk stasis is felt to play a role. Classically, this condition is noninfectious, but many cases are noted to be associated with Corynebacterium species. Most patients affected are parous women with a mean age of 35, and many have breastfed within five years of diagnosis. Patients typically present with a painful mass and symptoms of inflammation, and these features can sometimes mimic breast cancer. Biopsy is needed to make a definitive diagnosis, and noncaseating granulomas are found on core biopsy. Many patients have a waxing and waning course over a period of six months to two years. Goal of treatment is to avoid surgery given poor wound healing, high risk of recurrence, and poor cosmetic outcomes. Medical treatment is preferred and includes observation, antibiotics, steroids, and immune modulators such as methotrexate. In more recent years, topical and intralesional steroids have become the treatment of choice, with similar outcomes to oral steroids.

Endotracheal tubes with dexamethasone eluting electrospun coating improve tissue mechanical function after upper airway injury.

Corticosteroid-eluting endotracheal tubes (ETTs) were developed and employed in a swine laryngotracheal injury model to maintain airway patency and provide localized drug delivery to inhibit fibrotic scarring. Polycaprolactone (PCL) fibers with or without dexamethasone were electrospun onto the ETT surface PCL-only coated ETTs and placed in native airways of 18 Yorkshire swine. Regular and dexamethasone-PCL coated ETTs were placed in airways of another 18 swine injured by inner laryngeal mucosal abrasion. All groups were evaluated after 3, 7 and 14 days (n = 3/treatment/time). Larynges were bisected and localized stiffness determined by normal indentation, then sequentially matched with histological assessment. In the native airway, tissue stiffness with PCL-only ETT placement increased significantly from 3 to 7 days (p = 0.0016) and 3 to 14 days (p < 0.0001) while dexamethasone-PCL ETT placement resulted in stiffness decreasing from 7 to 14 days (p = 0.031). In the injured airway, localized stiffness at 14 days was significantly greater after regular ETT placement (23.1 ± 0.725 N/m) versus dexamethasone-PCL ETTs (17.10 ± 0.930 N/m, p < 0.0001). Dexamethasone-loaded ETTs were found to reduce laryngotracheal tissue stiffening after simulated intubation injury compared to regular ETTs, supported by a trend of reduced collagen in the basement membrane in injured swine over time. Findings suggest localized corticosteroid delivery allows for tissue stiffness control and potential use as an approach for prevention and treatment of scarring caused by intubation injury.