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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. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Cat‐scratch disease (CSD) is caused by Bartonella henselae and usually presents with regional lymphadenopathy. Skull base osteomyelitis and cerebral venous sinus thrombosis are rarely reported, particularly in immunocompetent children. CSD should be considered in the differential diagnosis of any patient with persistent headaches in the setting of cat exposure. [ABSTRACT FROM AUTHOR]

Keywords: featureless melanoma; SDDI; sequential digital dermatoscopic imaging; sequential digital dermoscopic imaging; TBP; total body photography EN featureless melanoma SDDI sequential digital dermatoscopic imaging sequential digital dermoscopic imaging TBP total body photography e193 e196 4 05/12/23 20230501 NES 230501 It is known that dermatoscopy improves diagnostic accuracy for skin lesions whether pigmented or not,[[1]] but it is also known that approximately 10% of melanomas are featureless, lacking diagnostic dermatoscopic criteria.[3] SP (page 620) sp Of relevance, a recent, appropriately powered and controlled study found that 59.2% of monitored lesions did not have dermatoscopic features of malignancy when excised, only being excised because of evident differences when sequential dermatoscopic images were compared side-by-side.[3] SP (page 619) sp Consistent with this, Australian melanoma guidelines highlight the role of both total body photography (TBP) and sequential digital dermatoscopic imaging (SDDI) but recommend as a "Practice Point" that TBP should be the I primary i imaging intervention for early melanoma detection in patients at elevated risk who have high naevus counts.[4] We present two cases of high-risk young patients, whose clinically and dermatoscopically subtle melanomas were first detected by operator-recognition of size-enlargement in sequential TBP images, these changes in both cases I not i being detected by dedicated software. SDDI, sequential digital dermatoscopic imaging, featureless melanoma, sequential digital dermoscopic imaging, TBP, total body photography Semi-automated total body photography can identify subtle melanomas but false-negatives on automated comparison highlight the need for manual side-by-side image comparison. [Extracted from the article]

Aim: Topography, climate and plant water stress influence the spatial patterns of burn severity (damage to soils and vegetation associated with wildfires); however, the relative importance of these predictors remains contested. We hypothesized that high‐resolution pre‐fire vegetation water stress, measured using evapotranspiration (ET), evaporative stress index (ESI) and water use efficiency (WUE), are strong predictors of burn severity. Location: California, USA. Time period: 2019–2020. Major taxa studied: Forests, chaparral, oaks and grasslands. Methods: We used random forest regression modelling with remotely sensed ECOsystem and Spaceborne Thermal Radiometer Experiment on Space Station (ECOSTRESS) plant water stress from the spring–summer and year before the fires, predictors to represent spatial autocorrelation, and topography to predict the spatial patterns of burn severity for six fires in the Sierra Nevada and the Southern California Mountains. Results: Plant water stress was the dominant predictor for the Southern California Mountains, and spatial autocorrelation in Sierra Nevada. Elevation was a leading predictor for burn severity for both regions, with greater predictability in higher‐elevation and steeper terrain. Model results varied by vegetation type: for the Southern California Mountains, grasslands had the highest predictability [R2 =.50 (high elevation); R2 =.58 (steep)], followed by savanna and open shrublands, which are typified by chaparral‐type vegetation [R2 =.43 (savanna, high elevation); R2 =.40 (open shrubland, high elevation)]. For grasslands, annual ET was the leading predictor (R2 =.58), consistent with the idea that growing season grassland enhancement increases fuel availability. The predictability of burn severity was also sensitive to the time of day of the ECOSTRESS acquisition and varied by vegetation type. Afternoon ET was the leading predictor for high‐elevation grasslands (R2 =.50), and morning predictors were important for steep‐sloped woody savanna (R2 =.18). Main conclusions Our findings provide insights on how antecedent plant water stress predicts burn severity and can inform pre‐fire season monitoring and fuel management. [ABSTRACT FROM AUTHOR]

Background: Institutional data on initiating and maintaining a low-titer O positive whole blood (LTOWB) inventory for the civilian trauma sector may help other institutions start a LTOWB program. This study from a level 1 trauma center with a hospital-based donor center highlights challenges faced during the collection, maintenance, and utilization of LTOWB.Study Design and Methods: Male O positive donors with low (≤1:100) anti-A and anti-B antibody titers were recruited for LTOWB collection. The daily inventory goal of 4 LTOWB units was kept in the emergency department refrigerator and transfused to adult male trauma patients. Unused units older than 10 days were reprocessed into packed red blood cells.Results: Of 900 donors screened, 61% qualified and 52% of eligible donors provided a collective total of 505 LTOWB units over 2.5 years. The number of collected units directly correlated with the availability of inventory; 42% of the units were transfused, 54% were reprocessed, and 4% were discarded. The inventory goal was maintained for 56% of the year 2018 and 83% of the year 2019. Over these 2 years, 52% of patients had their transfusion needs fully met, 41% had their needs partially met, and 6.5% did not have their needs met.Discussion: Initial challenges to LTOWB implementation were inventory shortages, low utilization rates, and failure to meet clinical demand. Proposed solutions include allowing for a higher yet safe titer, extending shelf life, expanding the donor pool, identifying barriers to utilization, and permitting use in female trauma patients beyond childbearing age. [ABSTRACT FROM AUTHOR]

Background: Norm‐correcting interventions are an effective alcohol harm‐reduction approach, but innovation is needed to increase modest effect sizes. Recent social psychology research shows that individuals may be influenced by social norms that are increasing in prevalence. Contrary to static norms that reflect the current state of normative behavior, dynamic norms reflect behavioral norms that are shifting over time. This proof‐of‐concept study tested the utility of dynamic norms messages within norm‐correcting interventions. Method: Undergraduate student drinkers (N = 461; Mage = 19.97; 64.43% female) were randomly assigned to receive (a) dynamic norms messages highlighting a steady decrease over the past six years in heavy drinking among college students; (b) static norms messaging stating only the current norms; or (c) a control condition without normative information. Proximal outcomes assessed immediately following the experimental paradigm included intentions for total weekly drinks and heavy episodic drinking. Self‐reported information on alcohol use behavior was collected at 1‐month follow‐up. Results: Following the experimental paradigm, participants in the dynamic norms condition estimated that future drinking norms would decrease, while those in the static norms and control groups estimated that future drinking norms would increase. Participants in the dynamic norms condition reported lower intentions for weekly drinks and heavy episodic drinking than those in the static norms and control conditions. No significant differences between conditions were found on alcohol use indices reported at the 1‐month follow‐up. However, dynamic norms messaging had a favorable indirect effect on heavy episodic drinking intentions mediated through lower perceived future drinking norms. Conclusions: These findings provide proof‐of‐concept that dynamic norms messaging may be a prudent strategy for reducing alcohol use intentions, which can be integrated into or used alongside existing norm‐correcting strategies. [ABSTRACT FROM AUTHOR]

This study utilizes satellite data to investigate water quality conditions in the San Francisco Estuary and its upstream delta, the Sacramento--San Joaquin River Delta. To do this, this study derives turbidity from the European Space Agency satellite Sentinel-2 acquired from September 2015 to June 2019 and conducts a rigorous validation with in situ measurements of turbidity from optical sensors at continuous monitoring stations. This validation includes 965 matchup comparisons between satellite and in situ sensor data across 22 stations, yielding R² = 0.63 and 0.75 for Nephelometric Turbidity Unit and Formazin Nephelometric Unit (FNU) stations, respectively. This study then applies remote sensing to evaluate patterns in turbidity during the Suisun Marsh Salinity Control Gates Action ("Gates action"), a pilot study designed to increase habitat access and quality for the endangered Delta Smelt. The basic strategy was to direct more freshwater into Suisun Marsh, creating more low salinity habitat that would then have higher (and more suitable) turbidity than upstream river channels. For all seven acquisitions considered from June 29 to September 27, 2018, turbidity conditions in Bays and Sloughs subregions were consistently higher (and more suitable) (26-47 FNU) than what was observed in the upstream River region (13-25 FNU). This overall pattern was observed when comparing images acquired during similar tidal stages and heights. [ABSTRACT FROM AUTHOR]

A 3D‐printed array of hollow microneedles (HMNs) is designed and fabricated using a high‐resolution stereolithography 3D printer and assembled with a 3D‐printed reservoir that incorporates a Luer lock mechanism, ensuring standard and secure connection to syringes. The proof‐of‐concept needle designs consist of half‐eccentric and concentric conical tip shapes, each arrayed with two different interspacing values. After the geometrical features of the devices are characterized, the devices are tested ex vivo in porcine skin to evaluate the impact of tip shape and interspacing on the depth of penetration and the efficacy of the devices in delivering fluids (such as tattoo ink) into the dermis. Overall, the 3D‐printed HMNs can deliver fluids into the target layer of skin. Refinement of the design is ongoing with the ultimate aim to provide alternatives for intradermal drug delivery and diagnostic imaging, such as superficial lymphography. [ABSTRACT FROM AUTHOR]

According to some recent analyses, the ethnographic encounter takes place between a complicit, colonialist, white discipline and "natives" who are colonized and implicitly nonwhite. But by insisting that anthropology is an inherently white discipline, such binary frameworks ultimately recenter Westernness and whiteness, reinforcing the centrality of Western and white anthropology. In doing so, they conflate phenotypic and structural whiteness, flatten out how anthropological whiteness compels nonwhite bodies to adopt a white habitus, and obfuscate the shifting, unstable role played by phenotype in this process. For anthropologists of color, even those born and trained in the West, the whiteness of anthropology is variable, context‐dependent, and unevenly distributed. This is illustrated with vignettes from ethnographic work in Peru, a country where racialization has typically been framed in terms of a white‐indigenous binary, and as operating like class rather than determined through descent or phenotype. [race, whiteness, ethnography, Asian American, Peru, Andes] [ABSTRACT FROM AUTHOR]

The article discusses the nomadic states in Mongolia that started from the late Bronze Age. Topics discussed include a comparison of the rise and maintenance of nomadic societies, egalitarian nomadic societies, the pattern of social-political development and multiple ethnicities in Central Asian nomadic states.

Objective: Within the UPPS‐P model of impulsive personality, negative urgency, positive urgency, lack of premeditation, lack of perseverance, and sensation seeking dimensions have been linked to unique etiological mechanisms and outcomes. Yet, additional research is needed exploring direct relations among dimensions to determine how these relations may contribute to the nature of impulsive personality and its correlates. The current study used network analysis to clarify relations among UPPS‐P dimensions and assess global robustness of these relations across young adulthood. Method: Participants included a longitudinal sample of 525 college students (48% male, 18–26 years) who completed the UPPS‐P once per year for three consecutive years. Results: Network structure was globally robust with particularly strong relations emerging between positive and negative urgency, as well as between lack of premeditation and lack of perseverance, across waves. Lack of premeditation consistently emerged as a central dimension. Additional analyses suggested lack of premeditation and sensation seeking as most robustly related with retrospectively reported frequency of alcohol use. Conclusions: Results suggested general robustness in the relations among impulsive personality dimensions, with relations involving lack of premeditation being particularly important for characterizing impulsive personality's nature. Sensation seeking and lack of premeditation may warrant particular focus when linking impulsive personality with frequency of alcohol use. [ABSTRACT FROM AUTHOR]

TE measures liver stiffness to assess fibrosis. Its use in post‐transplant patients was reported in few small pediatric studies. We evaluated TE ability to predict liver graft fibrosis in a large cohort while comparing it to the performance of APRI and FIB‐4. We also investigated the effect of graft type on LSMs. Patients at Boston Children's Hospital who underwent LT and LSM ≤ 1 year from biopsy (2007‐2018) were eligible. Ninety‐four patients (45%M) aged 1‐21 years (89% < 18 years; 13% < 2 years) were eligible. Median time between transplant/biopsy and LSM was 5.1 years and 52 days, respectively. Thirty‐nine percent received whole‐liver grafts, 54% TV grafts, and 6% as part of MV. At LSM, median ALT was 25 [IQR 16‐33] IU/L. Twenty‐one percent had METAVIR ≥ F2. LSM was statistically higher among those with significant fibrosis (METAVIR ≥ F2) compared to those with METAVIR F0/F1 (median [IQR] 7.5 [4.6, 13.6] vs 5.1 [4.0, 6.4] kPa, respectively) (P =.005 by Wilcoxon rank‐sum test). APRI and FIB‐4 distributions were not different across METAVIR stages. The AUROC for LSM was 0.71 (95% CI 0.56‐0.85) with an optimal cut‐point of 6.5 kPa. Graft type had no influence on the AUROC for LSM. TE is useful for assessing significant graft fibrosis in children and young adult LT recipients and performs better than APRI and FIB‐4. TV grafts demonstrate similar correlation with histology as whole‐liver grafts. [ABSTRACT FROM AUTHOR]

Platelets play a critical role in both haemostasis and thrombosis, and it is now evident that not all platelets behave the same when they are called to action. A functionally distinct subpopulation of platelets forms in response to maximal agonist stimulation: the procoagulant platelet. This platelet subpopulation is defined by its ability to expose phosphatidylserine on its surface, allowing for coagulation factor complexes to form and generate bursts of thrombin and fibrin to stabilize platelet clots. Reduced levels of procoagulant platelets have been linked to bleeding in Scott's syndrome and haemophilia A patients, and elevated levels have been demonstrated in many thrombotic disorders, including identifying patients at higher risk for stroke recurrence. One obstacle for incorporating an assay for measuring procoagulant platelets into clinical management algorithms is the lack of consensus on the exact definition and markers for this subpopulation. This review will outline the biological characteristics of procoagulant platelets and the laboratory assays currently used to identify them in research settings. It will summarize the findings of clinical research demonstrating the relevance of measuring the procoagulant platelet levels in patients and will discuss how an appropriate assay can be used to elucidate the mechanism behind the formation of this subpopulation, facilitating novel drug discovery to improve upon current outcomes in cardiovascular and other thrombotic disorders. [ABSTRACT FROM AUTHOR]

Background: Alcohol and marijuana are psychoactive substances commonly used by young adults and are independently associated with numerous acute and long‐term consequences. Many young adults engage in simultaneous alcohol and marijuana (SAM) use to cross‐fade (i.e., to enhance the effects of intoxication), although the extent to which alcohol use and alcohol‐related consequences increase on SAM occasions compared to alcohol‐only occasions is unclear. This study examines daily data among a sample of SAM users comparing SAM days to other days when young adults only used alcohol. Methods: A sample of 409 young adults (age 18 to 25; Mage = 21.6, SD = 2.2; 50.9% women) who reported SAM use in the past month completed 2 bursts of 14 days of daily surveys (28 days in total) assessing alcohol use, alcohol‐related consequences, and SAM use. Results: Multilevel models based on alcohol‐only and SAM days (n = 3,016 days; 391 individuals) indicated young adults drank more alcohol on SAM days compared to alcohol‐only days (with no marijuana use). Similarly, days with SAM use were associated with more alcohol‐related positive and negative consequences. The daily association between SAM use and positive consequences was statistically significant, after accounting for the amount of alcohol consumed; in contrast, the association between SAM use and negative consequences was diminished and nonsignificant. Conclusions: Among young adult SAM users, days with SAM use were associated with more alcohol use and positive consequences compared to days they only drank alcohol. Further examination of the motivational context for engaging in SAM use, as well as potential physiological interactions between alcohol and marijuana use on alcohol's effects, is warranted. Alcohol interventions might benefit from addressing increased alcohol use and alcohol‐related consequences as risks associated with SAM use. Many young adults engage in simultaneous alcohol and marijuana (SAM) use, although less is known about comparative risk of these days compared to days with alcohol‐only use. Multilevel models with two 14‐day bursts of daily data indicated young adults drank more alcohol on SAM days compared to alcohol‐only days. Similarly, days with SAM use were associated with more alcohol‐related positive and negative consequences, although the association with negative consequences was accounted for by the increase in alcohol use. [ABSTRACT FROM AUTHOR]

Vincristine is a cytotoxic chemotherapeutic agent used as first‐line therapy for pediatric acute lymphocytic leukemia. It is cleared by hepatic oxidative metabolism by CYP3A4 and CYP3A5 and via hepatic (biliary) efflux mediated by P‐glycoprotein (P‐gp) transporter. Bottom‐up physiologically based pharmacokinetic (PBPK) models were developed to predict vincristine disposition in pediatric and adult populations. The models incorporated physicochemical properties, metabolism by CYP3A4/5, efflux by P‐gp, and intracellular binding to β‐tubulin. The adult and pediatric PBPK models predicted pharmacokinetics (PK) within twofold of the observed PK parameters (area under the curve, terminal half‐life, volume of distribution, and clearance). Simulating a higher hypothetical (4.9‐fold) pediatric expression of β‐tubulin relative to adult improved predictions of vincristine PKs. To our knowledge, this is the first time that intracellular binding has been incorporated into a pediatric PBPK model. Utilizing this PBPK modeling approach, safe and effective doses of vincristine could be predicted. [ABSTRACT FROM AUTHOR]

Background: Previous research on peer status of children with attention‐deficit/hyperactivity disorder (ADHD) has focused on already‐established peer groups, rendering the specific social behaviors that influence peers' initial impressions largely unknown. Recently, theorists have argued that emotion dysregulation is a key aspect of ADHD, with empirical work finding relations between emotion dysregulation and social outcomes. Therefore, the current study focuses on the initial interactions among children varying in ADHD symptoms duringh a novel playgroup, proposing that emotion dysregulation displayed during the playgroup may serve as a possible pathway between ADHD symptoms and peers' initial negative impressions. Methods: Participants were 233 elementary‐age children ranging from 8 to 10 years old (M = 8.83, 70% male). Parents and teachers rated children's ADHD symptoms and related impairment; 51% of the children met criteria for an ADHD diagnosis. Then, children participated with unfamiliar peers in a three‐hour playgroup that included three structured and two unstructured tasks. After the tasks, children and staff rated each child on social outcomes. Coders unaware of child's diagnostic status watched videos of the groups and rated each child's global emotion dysregulation during each task. Results: Using multiple raters and methods, ADHD severity was associated with more negative peer ratings, through observed emotion dysregulation. Results were consistent for both parent and teacher ratings of ADHD severity as well as for both peer ratings of likeability and staff ratings of perceived peer likeability. Conclusions: When focusing on improving peers' initial impressions of children with ADHD symptoms, emotion dysregulation may be a valuable target for intervention. [ABSTRACT FROM AUTHOR]

Glucose homeostasis is closely regulated to maintain energy requirements of vital organs and skeletal muscle plays a crucial role in this process. Mustn1 is expressed during embryonic and postnatal skeletal muscle development and its function has been implicated in myogenic differentiation and myofusion. Whether Mustn1 plays a role in glucose homeostasis in anyway remains largely unknown. As such, we deleted Mustn1 in skeletal muscle using a conditional knockout (KO) mouse approach. KO mice did not reveal any specific gross phenotypic alterations in skeletal muscle. However, intraperitoneal glucose tolerance testing (IPGTT) revealed that 2‐month‐old male KO mice had significantly lower glycemia than their littermate wild type (WT) controls. These findings coincided with mRNA changes in genes known to be involved in glucose metabolism, tolerance, and insulin sensitivity; 2‐month‐old male KO mice had significantly higher expression of GLUT1 and GLUT10 transporters, MUP‐1 while OSTN expression was lower. These differences in glycemia and gene expression were statistically insignificant after 4 months. Identical experiments in female KO and WT control mice did not indicate any differences at any age. Our results suggest a link between Mustn1 expression and glucose homeostasis during a restricted period of skeletal muscle development/maturation. While this is an observational study, Mustn1's relationship to glucose homeostasis appears to be more complex with a possible connection to other key proteins such as GLUTs, MUP‐1, and OSTN. Additionally, our data indicate temporal and sex differences. Lastly, our findings strengthen the notion that Mustn1 plays a role in the metabolic capacity of skeletal muscle. [ABSTRACT FROM AUTHOR]

Background Marijuana policies are rapidly evolving. In the United States, recreational use of marijuana is now legal in 4 states and medical marijuana is legal in 23 states. Research evaluating such policies has focused primarily on how policies affect issues of price, access to, use, and consequences of marijuana. Due to potential spillover effects, researchers also need to examine how marijuana policies may impact use and consequences of alcohol. Methods The current paper is a critical review of articles evaluating alcohol outcomes associated with marijuana decriminalization, medical marijuana legalization, and nonmedical or recreational marijuana legalization. We identified articles and reports through (1) online searches of EBSCO host database including Academic Search Premier, Econlit, Legal Collection, Medline, PsycARTICLES, and Psyc INFO, as well as PubMed and Google Scholar databases; (2) review of additional articles cited in papers identified through electronic searches; and (3) targeted searches of state and local government records regarding marijuana law implementation. We reviewed studies with respect to their data sources and sample characteristics, methodology, and the margin of alcohol and marijuana use, timing of policy change, and the aspects of laws examined. Results The extant literature provides some evidence for both substitution (i.e., more liberal marijuana policies related to less alcohol use as marijuana becomes a substitute) and complementary (i.e., more liberal marijuana policies related to increases in both marijuana and alcohol use) relationships in the context of liberalization of marijuana policies in the United States. Conclusions Impact of more liberal marijuana policies on alcohol use is complex, and likely depends on specific aspects of policy implementation, including how long the policy has been in place. Furthermore, evaluation of marijuana policy effects on alcohol use may be sensitive to the age group studied and the margin of alcohol use examined. Design of policy evaluation research requires careful consideration of these issues. [ABSTRACT FROM AUTHOR]

Immigration is a frequently debated topic in American politics and media, yet little work examined children's understanding of this issue. In order to explore how children's understanding of immigration may differ based on their immigration experience, 261 elementary school-aged children (M = 9 years; SD = 1 year, 1 month) answered open-ended questions regarding why people move to the United States and why it should be legal or not. The sample consisted of 196 immigrants (first and second generation Latino/a immigrants) and 65 nonimmigrants (non-Latino/a children living in America for at least three generations). Children also rated possible explanations for societal antiimmigration attitudes. As predicted, Latino/a immigrant children explained immigration as a means of attaining concrete benefits for immigrants, such as improved education or jobs. They also referenced reuniting with family members in the U.S. Nonimmigrant children focused more on immigrants seeking American freedoms, reflecting the school-based curriculum explaining early European immigration to the U.S. Results reflect how differing experiences with immigration (direct or indirect) may influence perceptions towards immigration. [ABSTRACT FROM AUTHOR]

Background:Applicator conspicuity in ultrasound-guided brachytherapy procedures is commonly impaired by imaging artifacts or non-ideal imaging geometry, which can slow down applicator position digitization and increase the geometric uncertainty of the delivered dose distribution. Purpose: The purpose of this study was to improve the conspicuity of highdose rate (HDR) brachytherapy needles under B-mode ultrasound imaging by applying an echogenic surface coating. Our hypothesis was that an echogenic coating would reduce artifacts and improve needle visualization within regions of signal degradation. Methods: In this study, 17-gauge,25-cm long titanium HDR brachytherapy needles were coated with acoustically reflective microspheres over a 2.5 cm region starting from the needle tip. Three coating thicknesses (27 μm, 40 μm, 64 μm) were compared against an uncoated control needle. The coated and uncoated needles were imaged using B-mode ultrasound in a tissue-equivalent prostate phantom and in a cadaverous male pelvis using a transrectal probe. Needle conspicuity was assessed under multiple conditions: a single needle implant, an implant with multiple needles between the probe and the needle of interest, and an angled needle implant. All images were assessed qualitatively for needle conspicuity and the presence of artifacts and quantitatively using grey-scale image intensity values. Results: The 64 μm echogenic coating reduced the magnitude of reverberation artifacts by 31 ± 14% and comet tail artifacts by 40%–70%.The echogenic coating also improved needle contrast,measured by the relative differences in signal intensity compared with the adjacent environment, when needles were angled up to 30° with respect to the transducer probe in the cadaver. The improvements in conspicuity and artifact reduction increased with increasing coating thickness.The performance of the needles coated with the 64 μmthickness was qualitatively superior and yielded high-contrast,well-circumscribed signals in the cadaverous male pelvis, even under situations where a needle was acoustically shadowed by multiple other needles. Conclusions: An echogenic surface coating reduced imaging artifacts and improved needle conspicuity under realistic clinical conditions for ultrasoundbased prostate or gynecological brachytherapy. The improved conspicuity has the potential to improve the efficiency of needle placement and the accuracy of needle position digitization during brachytherapy procedures. [ABSTRACT FROM AUTHOR]

Objectives To determine whether older women with diabetes mellitus have a greater longitudinal decline in physical performance than those without and whether any decline differs according to insulin sensitizer use. Design Prospective cohort study. Setting Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela, Pennsylvania. Participants Community-dwelling women (mean age 78.5 ± 3.6) enrolled in the Study of Osteoporotic Fractures in 1997-98 and restudied 4.9 ± 0.6 years later (N = 2,864). Measurements Women were categorized as having no diabetes mellitus (n = 2,680) or having diabetes mellitus (n = 184). A prescription medication inventory was used to determine use of insulin sensitizers (metformin and thiazolidinedione). The outcomes were longitudinal changes in physical performance measures, including grip strength, usual walk speed, and rapid walk speed. Results Estimates from fully adjusted models showed that women with diabetes mellitus had greater declines in usual walk speed (−0.16 m/s, 95% confidence interval ( CI) = −0.19 to −0.14) and rapid walk speed (−0.21 m/s, 95% CI = −0.24 to −0.17) than those without (usual walk speed −0.11 m/s, 95% CI = −0.12 to −0.11, P < .001; rapid walk speed −0.15 m/s, 95% CI = −0.16 to −0.14; P = .005). Women with diabetes mellitus taking insulin sensitizers had less decline in usual walk speed than those not taking insulin sensitizers ( P < .001). Declines in grip strength did not differ significantly by diabetes mellitus status or insulin sensitizer use. Conclusion Older women with diabetes mellitus have a greater decline in walk speed, but not grip strength, than older women without diabetes mellitus. Clinical studies in older adults to determine whether diabetes mellitus treatments such as insulin sensitizers can prevent loss in walk speed and mobility are needed. [ABSTRACT FROM AUTHOR]

Background Textbooks play an important role in engineering education, influencing instructors' pedagogical approaches and providing much of the information students learn. Research has explored students' recollections of the roles that textbooks played in their educational experiences, but how students actually use textbooks remains largely unexplored. Purpose This phenomenological study describes engineering students' textbook use during problem-solving activities. This study directly examined how students employed a textbook in order to generate detailed descriptions of students' behaviors, approaches, and reflections regarding their actual problem-solving experiences. Method Ten senior materials engineering students (8 males and 2 females) were asked to think aloud while solving engineering problems. Follow-up retrospective interviews regarding the think aloud session were conducted to gain in-depth information on students' textbook use during the problem-solving activities. Results Students used the textbook primarily to find information related to problem constraints that were explicitly stated in the problem. Furthermore, textbook example problems exerted a strong influence on students' problem-solving processes. Students also reported limitations of the textbook, contrasting it to the diversity of resources available via the Internet. Conclusions This study provides insight into students' textbook use during engineering problem-solving activities. Students' limited application of the textbook during problem solving suggests that textbooks may not be serving their intended purposes. [ABSTRACT FROM AUTHOR]

The hen harrier ( Circus cyaneus) is a bird of prey that is persecuted in the United Kingdom, and there is a need for a DNA-based individual identification and sexing system for the use in forensic investigations. This study reports a new set of PCR primers for the chromo-helicase- DNA-binding protein 1 gene, which allows sexing using PCR- RFLP. Instead of exonic primers that amplify across a large intron, this set consists of a primer within the intron, enabling reduction in amplicon sizes from 356 to 212 bp and 565 to 219 bp in W and Z chromosomes. DNA degradation and dilution experiments demonstrate that this set is significantly more robust than one that amplifies across the intron, and sequencing of the intronic primer-binding region across several individuals shows that it is highly conserved. While our objective is to incorporate this primer set into an STR-based individualization kit, it may in the meantime prove useful in forensic or conservation studies. [ABSTRACT FROM AUTHOR]

Drawing from research that shows a positive relationship between multicultural experiences and creative cognition, the present study investigates creative thinking as a possible cognitive benefit gained from studying abroad. The domain generality and specificity of creative thinking is also explored. Undergraduate students completed a general measure and a culture specific measure of creative thinking. Performance on the two creative thinking tasks were compared between students who have studied abroad, students who are planning to study abroad, and students who have not and do not plan to study abroad. Results showed that students who studied abroad outperformed the two groups of students who did not study abroad on both the general and culture specific measures of creative thinking. Findings from this study provide evidence that studying abroad supports complex cognitive processes that underlie creative thinking in culture specific and domain general settings. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic has led to unprecedented life disruptions among young adults, including increased job insecurity and financial strain. Mental health problems and substance use have also increased during the pandemic, with young adults particularly vulnerable to experiencing these challenges. This study examines trajectories of financial distress among young adults during the pandemic and their associations with depression, anxiety, and hazardous alcohol and cannabis use. Data from 473 young adults (ages 22–29) recruited in the Northwest United States were collected from April/May 2020 to July/August 2021. Financial distress trajectories were identified using growth mixture modeling. Negative binomial models were used to examine associations between financial distress trajectories and distal outcomes of depression, anxiety, alcohol, and cannabis use. Three distinct trajectories were identified, revealing Low, Moderate, and High financial distress experiences. Individuals with "Moderate" and "High" trajectories showed significantly greater depressive and anxiety symptom scores compared with those in the "Low" financial distress trajectory group. Trajectories were not associated with subsequent levels of alcohol or cannabis use. Young adult mental health remains a priority during periods of economic downturn. Providers must be aware of the psychological challenges imposed by financial distress among young adults to address worsening mental health symptoms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

With the exception of Carabelli's trait, the European dentition is better known for the morphological traits that it does not exhibit rather than the ones that it does. One root trait, however, runs counter to the characterization of reduced and simplified European crowns and roots. Although a rare trait in general, two-rooted lower canines are much more common in Europeans than in any other regional grouping and, given adequate sample sizes, can be useful in evaluating gene flow between Europeans and neighboring groups. In European samples, two-rooted lower canines consistently exhibit frequencies of 5-8%. In our sample from northern Spain, the trait attains a frequency of almost 10%. In contrast, in Sub-Saharan Africans the trait is virtually unknown while in Asian and Asian-derived populations, it varies between 0.0 and 1.0%. Here we show that two-rooted canine frequencies for new migrants along the western frontiers of China and Mongolia ranged from 0-4%. These data suggest European-derived populations migrated into western China (Xinjiang Province) and Mongolia (Bayan Olgii Aimag) sometime during the late Bronze age (1000-400 BCE). Am J Phys Anthropol, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To examine the associations between insulin resistance and changes in body composition in older men without diabetes mellitus. DESIGN: Longitudinal cohort study of older men participating in the Osteoporotic Fractures in Men (MrOS) study. SETTING: Six U.S. clinical centers. PARTICIPANTS: Three thousand one hundred thirty-two ambulatory men aged 65 and older at baseline. MEASUREMENTS: Baseline insulin resistance was calculated for men without diabetes mellitus using the homeostasis model assessment of insulin resistance (HOMA-IR). Total lean, appendicular lean, total fat, and truncal fat mass were measured using dual energy X-ray absorptiometry scans at baseline and 4.6 ±0.3 years later in 3,132 men with HOMA-IR measurements. RESULTS: There was greater loss of weight, total lean mass, and appendicular lean mass and less gain in total fat mass and truncal fat mass with increasing quartiles of HOMA-IR (P<.001 for trend). Insulin-resistant men in the highest quartile had higher odds of 5% or more loss of weight (odds ratio (OR)=1.88, 95% confidence interval (CI)=1.46–2.43), total lean mass (OR=2.09, 95% CI=1.60–2.73) and appendicular lean mass (OR=1.57, 95% CI=1.27–1.95) and lower odds of 5% or more gain in total fat mass (OR=0.56, 95% CI=0.45–0.68) and truncal fat mass (OR=0.52, 95% CI=0.42–0.64) than those in the lowest quartile. These findings remained significant after accounting for age, site, baseline weight, physical activity, and change in physical activity. These associations were also independent of other metabolic syndrome features and medications. CONCLUSION: Greater lean mass loss and lower fat mass gain occurred in insulin-resistant men without diabetes mellitus than in insulin-sensitive men. Insulin resistance may accelerate age-related sarcopenia. [ABSTRACT FROM AUTHOR]

To evaluate risk of all-cause mortality associated with changes in body weight, total lean mass, and total fat mass in older men. Longitudinal cohort study. Six U.S. clinical centers. Four thousand three hundred thirty-one ambulatory men aged 65 to 93 at baseline. Repeated measurements of body weight and total lean and fat mass were taken using dual-energy X-ray absorptiometry 4.6 ± 0.4 years apart. Percentage changes in these measures were categorized as gain (+5%), loss (-5%), or stable (−5% to +5%). Deaths were verified centrally according to death certificate reviews, and proportional hazard models were used to estimate the risk of mortality. After accounting for baseline lifestyle factors and medical conditions, a higher risk of mortality was found for men with weight loss (hazard rat (HR)=1.84, 95% confidence interval (CI)=1.50-2.26), total lean mass loss (HR=1.78, 95% CI=1.45-2.19), and total fat mass loss (HR=1.72, 95% CI=1.34-2.20) than for men who were stable for each body composition measure. Men with total fat mass gain had a slightly greater mortality risk (HR=1.29, 95% CI=0.99-1.67) than those who remained stable. These associations did not differ according to baseline age, obesity, or self-reported health status ( P for interactions >.10), although self-reported weight loss intent altered mortality risks with total fat mass ( P for interaction=.04) and total lean mass ( P for interaction=.09) change. Older men who lost weight, total lean mass, or total fat mass had a higher risk of mortality than men who remained stable. [ABSTRACT FROM AUTHOR]

Abstract: While recent attention suggests that positive and negative alcohol-related expectancies are important determinants of alcohol use, less is known about what types of consequences young people report actually experiencing when drinking alcohol. The present study (N = 742, 54% women) examined positive (Fun/Social, Relaxation/Coping, Positive Image) and negative (Physical, Behavioral, Driving) consequences of alcohol use among individuals with prior drinking histories who completed surveys the summer before their first year at university. Fun/Social consequences were reported more frequently than any negative consequences. Alcohol consequences were associated with drinking behaviors. In particular, positive Fun/Social consequences and negative Physical and Driving-related consequences were related to alcohol frequency, alcohol quantity, and frequency of heavy episodic drinking. Positive consequences were at least as strongly associated with drinking as were negative consequences. The possible role of Fun/Social consequences in the escalation and maintenance of high-risk drinking is discussed. [ABSTRACT FROM AUTHOR]

The article focuses on the readership success of the journal "Haemophilia." The impact factor of the journal in 2006 is 3.073, a reflection on the quality of its articles. The 2006 articles of the journal were downloaded 115,564 times in the Blackwell's Synergy and other online hosts. The circulation of the journal continues to grow worldwide as indicated on its 5556 institutional subscriptions, 2761 consortia libraries with paid access and 2684 institutions in the developing countries.

This paper presents a flexible modern approach to handling concomitant information for estimating the relative potency parameter in quantitative bioassays. This is accomplished in a semi-parametric framework where the concomitant variable is included non-parametrically. Estimation is then performed using smoothing splines where the point and interval estimators of the relative potency parameter exhibits desirable asymptotic properties. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

To determine the prevalence of von Willebrand disease in women presenting with menorrhagia.Systematic review of studies evaluating the prevalence of von Willebrand disease in women with menorrhagia.Hospital outpatient clinics (mainly gynaecological) and population surveys.Women presenting with menorrhagia.Relevant studies were extracted from MEDLINE search, bibliographies of identified articles and published proceedings of meetings and conferences.Number of women with von Willebrand disease.Eleven studies were included, totalling 988 women with menorrhagia. One hundred and thirty-one women were diagnosed to have von Willebrand disease with prevalences in individual studies ranging from 5% to 24%. The overall prevalence was 13% (95% CI 11–15.6%). The prevalence was higher in the European studies—18% (95% CI 15–23%) compared with that in North American studies—10% (95% CI 7.5–13%). This difference (P= 0.007) is likely to be the result of differences in the studies, which include method of recruitment of study population, method of assessing menstrual blood loss ethnic composition of study population, criteria for diagnosis and use of race- and ABO blood group-specific values for von Willebrand factor.The prevalence of von Willebrand disease is increased in women with menorrhagia and is the underlying cause in a small but significant group of women with menorrhagia across the world. Testing for this disorder should be considered when investigating women with menorrhagia, especially those of Caucasian origin, those with no obvious pelvic pathology or with additional bleeding symptoms. [ABSTRACT FROM AUTHOR]

There are very few true breast emergencies. While infrequent, women do present to emergency departments or urgent care centres with breast‐related concerns. In this case‐based review, both common and uncommon urgent and emergent breast lesions are presented, emphasising ultrasound characteristics and imaging optimisation to improve accurate diagnosis and appropriate recommendations. [ABSTRACT FROM AUTHOR]

The use of protease inhibitor (PI) drugs in treatment regimens for HIV-infected patients with hereditary bleeding disorders has been associated with an increased bleeding tendency. To characterize the nature of this bleeding tendency, a retrospective case record analysis was performed on 67 HIV-positive patients with hereditary bleeding disorders who had been treated with PI therapy. 34 patients (51%) developed an increased bleeding tendency on PI therapy, usually within the first few weeks of treatment. As well as an increase in usual joint bleeds, patients developed spontaneous atypical small joint, soft tissue and muscle bleeds. Haematuria was also common. Bleeding episodes tended to respond suboptimally to factor concentrate replacement. Ritonavir was most likely to be associated with bleeding. Nine patients switched first-line PI therapy as a direct consequence of bleeding and seven had no further bleeding problem on their second PI. Factor concentrate usage was significantly increased during the first 6 months of PI therapy compared to the 6 months preceeding treatment. PI therapy is frequently associated with increased bleeding in patients with hereditary bleeding disorders. The mechanism of the bleeding tendency remains to be elucidated. [ABSTRACT FROM AUTHOR]

Interviews Rosemary Biggs, an expert on hemophilia and founder of the Hemophilia Centers. Development of a method to measure factor VIII, the factor lacking in hemophilia; Center's members; Difference between Christmas disease and hemophilia.

Key Points: ETD symptoms are present in 16% patients with underlying skull base pathology.Preoperative ETD symptoms improve following surgical treatment of skull base pathology.ETD symptoms may worsen in patients with central, posterior, or malignant skull base pathology. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Estuaries worldwide are experiencing stress due to increased droughts, which often prompt intervention by environmental managers and government agencies. Effective management of water resources in estuarine systems can be enhanced by new technologies and methodologies to support decision-making processes. Here, we evaluate the use of high-frequency, high-resolution satellite remote sensing within two managementrelevant case studies in the San Francisco Estuary and the Sacramento--San Joaquin River Delta. We used a remote sensing-derived time series of turbidity maps to (1) identify favorable turbidity conditions for the endangered fish species, delta smelt (Hypomesus transpacificus), during the height of the great California drought in the dry season of 2015, and (2) evaluate changes in turbidity following the installation of an emergency saltwater intrusion barrier. The mapping results indicate several persistent areas of turbidity refugia throughout the summer in the north and west Delta; however, there was infrequent connectivity. A comparison of images captured during ebb tides before and after barrier installation showed a mean increase of 6.6 Nephelometric Turbidity Units (NTU) in the San Joaquin River and 4 NTU in Fisherman's Cut. Our assessment of the barrier supports previous findings, which used field samples to conclude barrier installation may have resulted in increased turbidity near the barrier and enhances these findings by providing spatial context. [ABSTRACT FROM AUTHOR]

Introduction: Exposure to media with alcohol‐related content is a known risk for alcohol use and related harms among young people. The present study used longitudinal self‐report data on exposure to media with alcohol‐related content to examine age trajectories across young adulthood and to estimate associations with heavy episodic drinking (HED) and negative consequences. Method: Participants were 201 high‐risk young adults enrolled in 2‐ and 4‐year colleges (ages 18–25 at screening; 63.7% female). Repeated assessments occurred at four timepoints across a 12‐month period. Results: Self‐reported exposure to both positively and negatively portrayed alcohol‐related media content decreased with age. Between‐persons, controlling for alcohol use frequency, exposure to positive alcohol‐related media content was positively associated with HED, and exposure to negative alcohol‐related media content was inversely associated with HED; no within‐person effects on HED were significant. For negative consequences, controlling for alcohol quantity, exposure to positive media content was associated with more negative consequences both between‐ and within‐persons. Unexpectedly, exposure to negatively portrayed media content was positively associated with negative consequences at the within‐person level. Discussion and Conclusions: Trajectories in exposure to media with alcohol‐related content showed that relatively younger participants reported greater exposure, highlighting the need for policy and prevention efforts to protect this vulnerable demographic. Findings generally indicated that positive portrayals of alcohol use increase alcohol‐related risks. Moreover, increased exposure to negative portrayals in a given assessment was associated with more negative consequences—potentially by normalising or glorifying high‐risk drinking and consequences, though mechanistic/causal research is needed. [ABSTRACT FROM AUTHOR]

Mustn1, a gene expressed exclusively in the musculoskeletal system, was shown in previous in vitro studies to be a key regulator of myogenic differentiation and myofusion. Other studies also showed Mustn1 expression associated with skeletal muscle development and hypertrophy. However, its specific role in skeletal muscle function remains unclear. This study sought to investigate the effects of Mustn1 in a conditional knockout (KO) mouse model in Pax7 positive skeletal muscle satellite cells. Specifically, we investigated the potential effects of Mustn1 on myogenic gene expression, grip strength, alterations in gait, ex vivo investigations of isolated skeletal muscle isometric contractions, and potential changes in the composition of muscle fiber types. Results indicate that Mustn1 KO mice did not present any substantial phenotypic changes or significant variations in genes related to myogenic differentiation and fusion. However, an approximately 10% decrease in overall grip strength was observed in the 2‐month‐old KO mice in comparison to the control wild type (WT), but this decrease was not significant when normalized by weight. KO mice also generated approximately 8% higher vertical force than WT at 4 months in the hindlimb. Ex vivo experiments revealed decreases in about 20 to 50% in skeletal muscle contractions and about 10%–20% fatigue in soleus of both 2‐ and 4‐month‐old KO mice, respectively. Lastly, immunofluorescent analyses showed a persistent increase of Type IIb fibers up to 15‐fold in the KO mice while Type I fibers decreased about 20% and 30% at both 2 and 4 months, respectively. These findings suggest a potential adaptive or compensatory mechanism following Mustn1 loss, as well as hinting at an association between Mustn1 and muscle fiber typing. Collectively, Mustn1's complex roles in skeletal muscle physiology requires further research, particularly in terms of understanding the potential role of Mustn1 in muscle repair and regeneration, as well as with influence of exercise. Collectively, these will offer valuable insights into Mustn1's key biological functions and regulatory pathways. [ABSTRACT FROM AUTHOR]

Nodular amyloidosis (NA) is a rare type of primary localized cutaneous amyloidosis in which light chain amyloid deposits in the skin without concurrent systemic involvement. We report a challenging case of NA on the scalp, mimicking primary scarring alopecia, in a relatively young and healthy 36‐year‐old man. In addition to a nonspecific clinical appearance with a broad differential, NA can be a difficult diagnosis because it may require ancillary testing, such as liquid chromatography–tandem mass spectrometry to type the amyloid protein, and hematology–oncology workup to exclude systemic disease. Pathologists can highlight the importance of systemic evaluation in their reports to ensure patients receive appropriate management. [ABSTRACT FROM AUTHOR]

We examined patterns of longitudinal trajectories of loneliness during the COVID‐19 pandemic using six time points (January 2020 [pre‐pandemic] to March/April 2021) and whether trajectories were associated with psychological distress (depression/anxiety) and substance use (alcohol/cannabis) outcomes in Spring 2021. Participants were 644 young adults who completed online assessments. Outcomes were regressed on most‐likely loneliness trajectory adjusting for pre‐pandemic measures. Three loneliness trajectories varied from consistently lower to consistently higher. Pre‐pandemic social support was associated with lower odds of a higher loneliness trajectory. Higher loneliness trajectories were associated with greater odds of past‐month cannabis use compared to Low trajectories, but not significantly associated with depression, anxiety, or alcohol use in Spring 2021. Interventions addressing co‐occurring loneliness and cannabis use are needed. [ABSTRACT FROM AUTHOR]

Background: Simultaneous alcohol and marijuana (SAM) use has been associated with greater alcohol use and consequences at the daily level, but limited research has examined SAM use in relation to marijuana use and its consequences. This study tested daily associations between SAM use and four outcomes: alcohol use (number of drinks), marijuana use (hours high), negative alcohol consequences, and negative marijuana consequences. Methods: A community sample of young adults [ages 18–25, mean (SD) = 21.61 (2.17) years] with recent alcohol and SAM use was recruited (N = 409; 50.9% female; 48.2% non‐Hispanic/Latinx White). Participants completed a baseline survey and six 2‐week bursts of daily surveys (81.1% of morning surveys completed) and reported on substance use and negative substance‐related consequences. Multilevel modeling was used to test the main aims and to explore each specific consequence. Results: Among days with any alcohol use, SAM use days were associated with consuming more drinks and experiencing more total negative alcohol‐related consequences than non‐SAM use days. Among days with any marijuana use, SAM use days were associated with more hours being high than non‐SAM use days. Exploratory models showed that SAM use was related to five specific alcohol‐related consequences and two specific marijuana‐related consequences. Conclusions: These findings build upon prior research by showing that SAM use days are linked to consuming more drinks, reporting more hours being high from marijuana, and experiencing more total alcohol‐related consequences even after controlling for the number of drinks, the number of hours high, any tobacco/nicotine use, and any other substance use. SAM use was also associated with a greater likelihood of experiencing some specific consequences related to alcohol and marijuana. The findings underscore the need for additional research on SAM use and marijuana‐related outcomes. The current study found that, among days with any alcohol use, SAM use days were associated with consuming more drinks and experiencing more total alcohol consequences and also experiencing some specific alcohol consequences. Among days with any marijuana use, SAM use days were associated with more hours high and experiencing some specific marijuana consequences. Findings build on prior research by showing effects of SAM use even after controlling for number of drinks, number of hours high, and other substance use. [ABSTRACT FROM AUTHOR]

Objective: Inhalational burns frequently lead to dysphonia and airway stenosis. We hypothesize local dexamethasone delivery via a novel drug‐eluting electrospun polymer‐mesh endotracheal tube (ETT) reduces biomechanical and histologic changes in the vocal folds in inhalational burn. Methods: Dexamethasone‐loaded polymer mesh was electrospun onto ETTs trimmed to transglottic endolaryngeal segments and secured in nine Yorkshire Crossbreed swine with directed 150°C inhalation burns. Uncoated ETTs were implanted in nine additional swine with identical burns. ETT segments were maintained for 3 and 7 days. Vocal fold (VF) structural stiffness was measured using automated‐indentation mapping and compared across groups and to four uninjured controls, and matched histologic assessment performed. Statistical analysis was conducted using two‐way ANOVA with Tukey's post hoc test and Wilcoxon rank‐sum test. Results: VF stiffness after burn decreased with longer intubation, from 19.4 (7.6) mN/mm at 3 days to 11.3 (5.2) mN/mm at 7 days (p <.0001). Stiffness similarly decreased with local dexamethasone, from 25.9 (17.2) mN/mm at 3 days to 18.1 (13.0) mN/mm at 7 days (p <.0001). VF stiffness in the dexamethasone group was increased compared to tissues without local dexamethasone (p =.0002), and all groups with ETT placement had higher tissue stiffness at 3 days (p <.001). No significant change in histologic evidence of epithelial ulceration or fibrosis was noted, while an increased degree of inflammation was noted in the dexamethasone group (p =.04). Conclusion: Local dexamethasone delivery increases VF stiffness and degree of inflammation compared to uncoated ETTs in an acute laryngeal burn model, reflected in early biomechanical and histologic changes in an inhalational burn model. [ABSTRACT FROM AUTHOR]

Background: The contexts in which young adults drink alcohol play a salient role in alcohol‐related outcomes and negative consequences at an event‐level, but less is known about longitudinal risks. We collected longitudinal monthly data across 2 years on (a) daytime drinking, (b) pregaming/pre‐partying, and (c) playing drinking games. We then examined associations between drinking in these contexts and within‐person variability in alcohol consumption, consequences, and simultaneous alcohol and marijuana (SAM) use in a given month. We also examined the extent to which drinking in these contexts predicted hazardous drinking (using Alcohol Use Disorders Identification Test (AUDIT) scores) at a distal follow‐up timepoint, controlling for baseline AUDIT scores. Method: A community sample of 759 young adults (Mage = 21.1 years; 56.4% female) completed monthly surveys for 24 consecutive months and a distal 30‐month follow‐up. Multilevel models estimated within‐ and between‐person associations between drinking context frequencies (daytime drinking, pregaming, drinking games) and alcohol‐related outcomes (weekly consumption, consequences, SAM use). A single‐level negative binomial regression tested associations between drinking context frequency averages across a two‐year period and changes in AUDIT scores from baseline to a follow‐up 2.5 years later. Results: Over 75% of the sample of non‐abstaining young adults reported drinking in each of the three contexts at least once during the 24‐month period. Within‐persons, young adults reported greater consumption, more negative consequences, and increased likelihood of SAM use during months that they drank in these contexts more often than usual. Each context was associated with negative consequences, even when controlling for alcohol use frequency. More frequent daytime drinking and pregaming, but not drinking games, were associated with increases in AUDIT scores at the 30‐month follow‐up, suggesting that there are potential long‐term risks of drinking in these contexts. Conclusions: Findings suggest that daytime drinking, pregaming, and playing drinking games are high‐risk contexts in terms of month‐to‐month and long‐term risks. Additional research is needed on the various contexts in which young adults drink alcohol and the extent to which contextual factors interact with one another to amplify/reduce risks and harms. [ABSTRACT FROM AUTHOR]