2-Aminophenanthroline Ligands Enable Mild, Undirected, Iridium-Catalyzed Borylation of Alkyl C-H Bonds.

The catalytic, undirected borylation of alkyl C-H bonds typically occurs at high reaction temperatures or with excess substrate, or both, because of the low reactivity of alkyl C-H bonds. Here we report a new iridium system comprising 2-anilino-1,10-phenanthroline as the ligand that catalyzes the borylation of alkyl C-H bonds with little to no induction period and with high reaction rates. This superior activation and reactivity profile of 2-aminophenanthroline-ligated catalysts leads to broader reaction scope, including reactions of sensitive substrates, such as epoxides and glycosidic acetals, enhanced diastereoselectivity, and higher yields of borylated products. These catalysts also enable the borylation of alkanes, amines, and ethers at room temperature for the first time. Mechanistic studies imply that facile N-borylation occurs under the reaction conditions and that iridium complexes containing N-boryl aminophenanthrolines are competent precatalysts for the reaction.

Intrapatient comparison of atopic dermatitis skin transcriptome shows differences between tape-strips and biopsies.

BACKGROUND: Our knowledge of etiopathogenesis of atopic dermatitis (AD) is largely derived from skin biopsies, which are associated with pain, scarring and infection. In contrast, tape-stripping is a minimally invasive, nonscarring technique to collect skin samples. METHODS: To construct a global AD skin transcriptomic profile comparing tape-strips to whole-skin biopsies, we performed RNA-seq on tape-strips and biopsies taken from the lesional skin of 20 moderate-to-severe AD patients and the skin of 20 controls. Differentially expressed genes (DEGs) were defined by fold-change (FCH) ≥2.0 and false discovery rate <0.05. RESULTS: We detected 4104 (2513 Up; 1591 Down) and 1273 (546 Up; 727 Down) DEGs in AD versus controls, in tape-strips and biopsies, respectively. Although both techniques captured dysregulation of key immune genes, tape-strips showed higher FCHs for innate immunity (IL-1B, IL-8), dendritic cell (ITGAX/CD11C, FCER1A), Th2 (IL-13, CCL17, TNFRSF4/OX40), and Th17 (CCL20, CXCL1) products, while biopsies showed higher upregulation of Th22 associated genes (IL-22, S100As) and dermal cytokines (IFN-γ, CCL26). Itch-related genes (IL-31, TRPV3) were preferentially captured by tape-strips. Epidermal barrier abnormalities were detected in both techniques, with terminal differentiation defects (FLG2, PSORS1C2) better represented by tape-strips and epidermal hyperplasia changes (KRT16, MKI67) better detected by biopsies. CONCLUSIONS: Tape-strips and biopsies capture overlapping but distinct features of the AD molecular signature, suggesting their respective utility for monitoring specific AD-related immune, itch, and barrier abnormalities in clinical trials and longitudinal studies.

Clinical and molecular effects of oral CCR4 antagonist RPT193 in atopic dermatitis: A Phase 1 study.

BACKGROUND: RPT193 is an orally administered small molecule antagonist of the human C-C motif chemokine receptor 4 (CCR4) that inhibits the migration and downstream activation of T-helper Type 2 (Th2) cells. We investigated single- and multiple-ascending doses of RPT193 in healthy subjects, and multiple doses of RPT193 in subjects with moderate-to-severe atopic dermatitis (AD). METHODS: This was a first-in-human randomized, placebo-controlled Phase 1a/1b monotherapy study (NCT04271514) to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and CCR4 surface receptor occupancy in eligible healthy subjects and subjects with moderate-to-severe AD. Clinical efficacy and skin biomarker effects of RPT193 monotherapy were assessed as exploratory endpoints in AD subjects. RESULTS: In healthy (n = 72) and AD subjects (n = 31), once-daily RPT193 treatment was generally well tolerated, with no serious adverse events reported and all treatment-emergent adverse events reported as mild/moderate. In AD subjects, numerically greater improvements in clinical efficacy endpoints were observed with RPT193 monotherapy versus placebo up to the end of the treatment period (Day 29), with statistically significant improvement, compared to Day 29 and placebo, observed 2 weeks after the end of treatment (Day 43) on several endpoints (p < .05). Moreover, significant changes in the transcriptional profile were seen in skin biopsies of RPT193-treated versus placebo-treated subjects at Day 29, which were also significantly correlated with improvements in clinical efficacy measures. CONCLUSIONS: To our knowledge, this is the first clinical study with an oral CCR4 antagonist that showed clinical improvement coupled with modulation of the cutaneous transcriptomic profile in an inflammatory skin disease.

Alcohol Use Disorder Polygenic Risk Scores and Trajectories of Early Adolescent Externalizing Behaviors: Examining the Role of Parenting and Family Conflict in the Racially/Ethnically Diverse ABCD Sample.

This study examined the independent and interactive effects of alcohol use disorder genome-wide polygenic scores (AUD-PGS) and parenting and family conflict on early adolescent externalizing behaviors. Data were drawn from White (N = 6181, 46.9% female), Black/African American (N = 1784, 50.1% female), and Hispanic/Latinx (N = 2410, 48.0% female) youth from the adolescent brain cognitive development Study (ABCD). Parents reported on youth externalizing behaviors at baseline (T1, age 9/10), 1-year (T2, age 10/11) and 2-year (T3, age 11/12) assessments. Youth reported on parenting and family environment at T1 and provided saliva or blood samples for genotyping. Results from latent growth models indicated that in general externalizing behaviors decreased from T1 to T3. Across all groups, higher family conflict was associated with more externalizing behaviors at T1, and we did not find significant associations between parental monitoring and early adolescent externalizing behaviors. Parental acceptance was associated with lower externalizing behaviors among White and Hispanic youth, but not among Black youth. Results indicated no significant main effect of AUD-PGS nor interaction effect between AUD-PGS and family variables on early adolescent externalizing behaviors. Post hoc exploratory analysis uncovered an interaction between AUD-PGS and parental acceptance such that AUD-PGS was positively associated with externalizing rule-breaking behaviors among Hispanic youth, but only when parental acceptance was very low. Findings highlight the important role of family conflict and parental acceptance in externalizing behaviors among early adolescents, and emphasize the need to examine other developmental pathways underlying genetic risk for AUD across diverse populations.

Mental Health Needs of Inpatient Psychiatric Nurses During the COVID-19 Pandemic.

INTRODUCTION: The lack of mental health supports and resources for psychiatric nurses during the COVID-19 pandemic contributed to stress, burnout, and reduced mental wellness. Simultaneously, the pandemic's safety mitigation measures made significant changes to the inpatient psychiatric population environment making it difficult to maintain a therapeutic milieu and increased mental health challenges among staff and patients. AIMS: This study aimed to identify external and internal resilience factors, mental health support, and resources provided by organizations, and additional mental health support and resources inpatient psychiatric nurses felt would have been beneficial during the pandemic. METHODS: An anonymous web-based survey was administered via American Psychiatric Nurses Association Member Bridge. Notably, 68 respondents represented 23 states across the United States. RESULTS: Interpersonal peer relationships, self-awareness, self-care, mindfulness, and purpose were identified resilience factors. Free counseling, decompression rooms, pastoral support, self-care discounts, and support groups were top support and resource options. Policies, time-off, personal protective equipment (PPE) availability, counseling and self-care, and appreciation were major themes reflecting what participants thought would have been beneficial. Coping strategies, organizational support, resilience, altruism, and family and peer support were instrumental in psychiatric nurses' survival during the pandemic. CONCLUSION: Identifying factors of resilience is key to supporting and protecting the mental health of psychiatric nurses. Organizations can better support their nurses when they understand what mental health support and resource options are perceived as most beneficial by inpatient nurses.

Age of onset defines two distinct profiles of atopic dermatitis in adults.

BACKGROUND: The incidence of adult-onset atopic dermatitis (AOAD) is increasing. However, the unique characteristics of AOAD compared to pediatric-onset AD persisting into adulthood (POAD) are underexplored, hampering the development of targeted-therapeutics for this growing population. We thus assessed the profile of AOAD in skin and blood compared to that of POAD. METHODS: We collected skin biopsies and blood from adults with AOAD, POAD, and healthy controls (n = 15 in each group). Skin samples were analyzed by RNA sequencing, qRT-PCR, and immunohistochemistry, and Olink Proseek multiplex assay was used to identify the serum proteomic profile. RESULTS: Compared to healthy controls, both AOAD and POAD showed cutaneous immune and barrier dysregulations with a shared Th2/Th22 hyperactivation. Overall, POAD showed greater inflammation in lesional skin, with more prominent expression of Th2/Th17/Th22 markers (CCL17/22, S100A8/9, IL-36A, PI3/Elafin, DEFB4) in POAD compared to AOAD (p-value < .05). In contrast, higher Th1-(IFN-γ, IL-2, IL-15, CCL5) upregulation and Th1-skewing were seen in AOAD. The epidermal barrier was also more compromised in POAD, with greater epidermal hyperplasia and lower expression of markers related to terminal differentiation, lipids, and cell adhesion. In parallel with increased rates of cardiovascular comorbidities, AOAD demonstrated many more significantly dysregulated proteins in serum (n = 148) compared to POAD (n = 86), including pro-inflammatory and cardiovascular-risk markers. Th1-related products showed significant correlations between their skin and blood expressions only in AOAD subjects. CONCLUSION: Age-of-onset delineates two distinct endophenotypes in adult AD potentially suggesting the need for broader (beyond Th2) therapeutic targeting in AOAD.

Scalp biomarkers during dupilumab treatment support Th2 pathway pathogenicity in alopecia areata.

BACKGROUND: The mechanisms driving alopecia areata (AA) are still unclear, hindering development of targeted therapeutics. Specific Th2 targeting with dupilumab in AA provides a unique opportunity to dissect its pathogenesis and explore the role of Th2 pathway. METHODS: We evaluated changes in scalp biomarkers in AA patients (with and without concomitant atopy) randomized to weekly dupilumab or placebo for 24 weeks, followed by open-label dupilumab for 24 weeks. Changes in biomarker levels were measured at weeks 12, 24, and 48 and were also correlated with clinical hair regrowth. RESULTS: At week 24, preceding clinical hair regrowth outcomes, only dupilumab-treated patients presented significant suppression of cellular infiltrates, and multiple Th2-related, markers (CCL13/MCP-4, CCL18/PARC, CCL26/eotaxin-3, CCL24/Eotaxin-2), coupled with significant upregulation in the hair keratins. Th1-related suppression was evident later (week 48) when all patients received open-label dupilumab. Results were more pronounced in atopic AA patients, that showed 48% and 97% improvements in the lesional AA scalp profile at weeks 24 and 48, respectively, while 2% worsening was seen in the placebo arm at week 24. Moreover, placebo-treated patients presented 54% worsening in hair keratins when compared with baseline at week 24. At week 24, increases in hair keratins showed significant correlations only with decreases in Th2-related markers. CONCLUSIONS: Scalp biomarkers provide evidence of dupilumab efficacy in AA, detected even prior to clinical response, with exclusive correlations between early suppression of Th2 markers and increased hair keratins. These findings strengthen previous reports suggesting a possible role for Th2 cytokines as AA drivers.

Fetal growth trajectories of babies born large-for-gestational age in the LIFECODES Fetal Growth Study.

BACKGROUND: Babies born large-for-gestational age have an increased risk of adverse health outcomes, including birth injuries, childhood obesity, and cardiometabolic disorders. However, little work has been done to characterize patterns of fetal growth among large-for-gestational age births, which may further elucidate high- and low-risk subgroups. OBJECTIVE: This study aimed to identify subgroups of large-for-gestational age births based on trajectories of fetal growth derived from prenatal ultrasound measurements and explore differences in sociodemographic, pregnancy, and birth outcome characteristics across subgroups. STUDY DESIGN: This study identified and described trajectories of fetal growth among large-for-gestational age births (n=235) in the LIFECODES Fetal Growth Study. Ultrasound measurements of fetal growth in middle to late pregnancy were abstracted from health records. Group-based multi-trajectory modeling was applied to measurements of head circumference, abdominal circumference, and femur length z-scores to identify multivariate trajectories of fetal growth. Moreover, sociodemographic variables, pregnancy characteristics, and birth outcomes based on trajectory membership were summarized. RESULTS: This study identified 4 multivariate trajectories of fetal growth among large-for-gestational age births: catch-up growth (n=28), proportional abdominal circumference-to-femur length growth (n=67), disproportional abdominal circumference-to-femur length growth (n=96), and consistently large (n=44). Fetuses in the "catch-up growth" group exhibited small relative sizes in midpregnancy (ie, below average head circumference, abdominal circumference, and femur length z-scores) and large relative sizes in late pregnancy. Growth among these births was driven by increases in relative abdominal circumference and head circumference sizes. Participants who delivered births assigned to this group were less likely to have normal glucose control (40% vs 65%-75%) and more likely to have pregestational diabetes mellitus (36% vs 10%-17%) than other large-for-gestational age subgroups. In addition, the babies in this trajectory group were more likely to have macrosomia (86% vs 67%-73%) and to be admitted to the neonatal intensive care unit (32% vs 14%-21%) than other large-for-gestational age subgroups. In contrast, babies in the "consistently large" group had the largest relative size for all growth parameters throughout gestation and experienced a lower risk of adverse birth outcomes than other large-for-gestational age subgroups. CONCLUSION: This study characterized several trajectories of fetal growth among large-for-gestational age births, which were related to different pregnancy characteristics and the distribution of adverse birth outcomes. Although the number of individuals within some trajectories was small, a subgroup that exhibited a catch-up growth phenotype during gestation was identified, which may be uniquely associated with exposure to pregestational diabetes mellitus and a higher risk of admission to the neonatal intensive care unit. These results have highlighted that the risk of adverse outcomes may not be evenly distributed across all large-for-gestational age births.

An application of group-based trajectory modeling to define fetal growth phenotypes among small-for-gestational-age births in the LIFECODES Fetal Growth Study.

BACKGROUND: Reductions in fetal growth are associated with adverse outcomes at birth and later in life. However, identifying fetuses with pathologically small growth remains challenging. Definitions of small-for-gestational age are often used as a proxy to identify those experiencing pathologic growth (ie, fetal growth restriction). However, this approach is subject to limitation as most newborns labeled small-for-gestational age are constitutionally, not pathologically, small. Incorporating repeated ultrasound measures to examine fetal growth trajectories may help distinguish pathologic deviations in growth from normal variability, beyond a simple definition of small-for-gestational age. OBJECTIVE: This study aimed to characterize phenotypes of growth using ultrasound trajectories of fetal growth among small-for-gestational-age births. STUDY DESIGN: This study identified and described trajectories of fetal growth among small-for-gestational-age births (<10th percentile weight for gestational age; n=245) in the LIFECODES Fetal Growth Study using univariate and multivariate trajectory modeling approaches. Available ultrasound measures of fetal growth (estimated fetal weight, head circumference, abdominal circumference, and femur length) from health records were abstracted. First, univariate group-based trajectory modeling was used to define trajectories of estimated fetal weight z scores during gestation. Second, group-based multi-trajectory modeling was used to identify trajectories based on concurrent measures of head circumference, abdominal circumference, and femur length z scores. Last, how these trajectories were related to patient demographics, pregnancy characteristics, and birth outcomes compared with those observed among appropriate-for-gestational-age controls was described. RESULTS: Of note, 3 univariate trajectories of estimated fetal weight and 4 multivariate trajectories of fetal growth among small-for-gestational-age births were identified. In our univariate approach, infants with the smallest estimated fetal weight trajectory throughout pregnancy had poorer outcomes, including the highest risk of neonatal intensive care unit admission. The remaining univariate trajectory groups did not have an elevated risk of adverse birth outcomes relative to appropriate-for-gestational-age controls. In our multivariate approach, 2 groups at increased or moderately increased risk of neonatal intensive care unit admission were identified, including infants that remained extremely small for all parameters throughout pregnancy and those who had disproportionately smaller femur length and abdominal circumference compared with head circumference. The remaining multivariate trajectory groups did not have an elevated risk of adverse birth outcome relative to appropriate-for-gestational-age controls. CONCLUSION: Latent class group-based trajectory modeling applied to ultrasound measures of fetal growth may help distinguish pathologic vs constitutional growth profiles among newborns born small-for-gestational age. Although trajectories cannot be fully characterized until delivery, limiting the direct clinical application of these methods, they may still contribute to the development of approaches for separating growth restriction from constitutional smallness.

Cross-Sectional Study of Psoriasis, Atopic Dermatitis, Rosacea, and Alopecia Areata Suggests Association With Cardiovascular Diseases.

BACKGROUND: A growing body of evidence suggests that several inflammatory skin diseases (ISDs) are associated with systemic inflammation and cardiovascular disease (CVDs). METHODS: We used the TriNetX analytics platform to conduct a retrospective, cross-sectional, single-center study in the Mount Sinai Health System network. Cases (all patients ≥18 years of age with a diagnosis of 1 of the 4 ISDs studied) were compared with matched controls (no history of any of these ISDs) to evaluate odds ratios for being diagnosed with CVD. RESULTS: We identified a total of 70,090 patients with ISDs, including 35,160 patients with atopic dermatitis, 19,490 with psoriasis, 12,470 with rosacea, and 2,970 with alopecia areata, and 70,090 propensity score-matched controls without any of these ISDs. Patients with atopic dermatitis and psoriasis had significantly increased odds of all CVD diagnoses analyzed compared to controls (P<0.001 for all comparisons). Patients with rosacea had significantly increased odds of being diagnosed with all diseases of the circulatory system (P<0.001), hypertensive diseases (P<0.001), cerebrovascular diseases (P=0.037), and arterial disease (P<0.001) compared to controls. Patients with alopecia areata had increased odds for all diseases of the circulatory system (P<0.001), hypertensive diseases (P<0.001), and arterial disease (P<0.001). The prevalence of patients with elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels was significantly greater in all ISD groups compared to controls. CONCLUSION: This study identified significant associations between ISDs and several CVD diagnoses. Furthermore, CRP and ESR were elevated in all ISD groups compared to controls. Pagan AD, Jung S, Caldas S, et al. Cross-sectional study of psoriasis, atopic dermatitis, rosacea, and alopecia areata suggests association with cardiovascular diseases. J Drugs Dermatol. 2023;22(6):576-581. doi:10.36849/JDD.7424.

Seasonal Patterns in Tetracycline-Associated Hyperpigmentation Among Patients With Acne Vulgaris.

BACKGROUND: Oral tetracyclines (TCNs) are commonly prescribed for acne, but they have been shown to increase the risk of hyperpigmentation, particularly in the setting of sun exposure. OBJECTIVE: We evaluated seasonal trends in TCN-associated hyperpigmentation incidence in addition to Google search trends for hyperpigmentation-related terms. METHODS: We performed a retrospective review of acne patients seen at Massachusetts General Brigham and Women’s Hospital between 1992 and 2022. We calculated the incidence of new hyperpigmentation diagnoses for each drug cohort. We also analyzed search volume of hyperpigmentation-related terms extracted from Google Trends. RESULTS: Seasonal differences in new hyperpigmentation diagnoses were identified among acne patients prescribed doxycycline (P=0.016), with peak incidence in April. In the control group of patients who had never received a TCN, diagnoses peaked in May. There were no significant seasonal differences among patients prescribed minocycline (P=0.885). There was greater search volume for hyperpigmentation-related terms in spring and summer compared to fall and winter (P<0.001). Limitations of this study include its retrospective nature and reliance on prescription and diagnosis coding data. CONCLUSIONS: Our findings support the seasonal periodicity of acne-related hyperpigmentation, underscoring the importance of photoprotection counseling for patients with acne. Additionally, doxycycline may be associated with an earlier onset of hyperpigmentation, suggesting a potential benefit of considering minocycline or other alternatives to doxycycline. J Drugs Dermatol. 2023;22(11):e9-e11    doi:10.36849/JDD.7409e.

Associations between mixtures of urinary phthalate metabolite concentrations and oxidative stress biomarkers among couples undergoing fertility treatment.

Phthalate exposure has been associated with adverse reproductive outcomes and oxidative stress is a potential mechanism by which they act. However, few human studies have explored co-exposure confounding or joint effects. Furthermore, most studies examine associations between biomarkers of exposure and oxidative stress from the same urine sample. We investigated single-exposure, co-exposure-adjusted, and joint associations between phthalate metabolites and oxidative stress in the Environment and Reproductive Health (EARTH) study among couples undergoing fertility treatment. We examined cross-sectional associations in both women and men, and longitudinal associations in women. Urine was collected in the follicular phase (women only) and at the time of fertility procedure (women and men), and analyzed for 11 phthalate metabolites. Urine from the time of fertility procedure was analyzed for oxidative stress biomarkers, including free 8-iso-prostaglandin F2α (8-iso-PGF2α), its primary metabolite (2,3-dinor-5,6-dihydro-15-F2t-isoprostane [F2-IsoP-M]), and prostaglandin F2α (PGF2α). Linear mixed effects models were used to estimate single-exposure associations. Bayesian Kernel Machine Regression (BKMR) was used to adjust for co-exposures and to estimate joint effects. Among women, we observed positive associations between all phthalate metabolites and oxidative stress biomarkers in single-exposure models, but there was clear co-exposure confounding. For instance, in a single-exposure model, we estimated a 63% (95% confidence interval: 51, 77) increase in the 8-iso-PGF2α metabolite per interquartile range (IQR) difference in mono-n-butyl phthalate (MBP) versus a 34% (95% credible interval: 12, 60) increase in co-adjusted models. However, several phthalate metabolites remained associated with oxidative stress in co-exposure models, and the joint effects of all exposures were high (e.g., an 114% increase in the 8-iso-PGF2α metabolite per IQR difference in all exposures). Longitudinal results were also attenuated compared to cross-sectional results in women; however, the joint effect of all exposures and the 8-iso-PGF2α metabolite remained positive and statistically significant (11% increase per IQR difference in all exposures, 95% credible interval: 0.2, 23). In men, associations were generally less pronounced, although the joint effect of the mixture on 8-iso-PGF2α was above the null. Because oxidative stress is related to reproductive success among couples seeking fertility treatment, mitigating phthalate exposure should be considered as a potentially beneficial measure.

A Novel Domain Transfer-Based Approach for Unsupervised Thermal Image Super-Resolution.

This paper presents a transfer domain strategy to tackle the limitations of low-resolution thermal sensors and generate higher-resolution images of reasonable quality. The proposed technique employs a CycleGAN architecture and uses a ResNet as an encoder in the generator along with an attention module and a novel loss function. The network is trained on a multi-resolution thermal image dataset acquired with three different thermal sensors. Results report better performance benchmarking results on the 2nd CVPR-PBVS-2021 thermal image super-resolution challenge than state-of-the-art methods. The code of this work is available online.

On the Prediction of In Vitro Arginine Glycation of Short Peptides Using Artificial Neural Networks.

One of the hallmarks of diabetes is an increased modification of cellular proteins. The most prominent type of modification stems from the reaction of methylglyoxal with arginine and lysine residues, leading to structural and functional impairments of target proteins. For lysine glycation, several algorithms allow a prediction of occurrence; thus, making it possible to pinpoint likely targets. However, according to our knowledge, no approaches have been published for predicting the likelihood of arginine glycation. There are indications that arginine and not lysine is the most prominent target for the toxic dialdehyde. One of the reasons why there is no arginine glycation predictor is the limited availability of quantitative data. Here, we used a recently published high-quality dataset of arginine modification probabilities to employ an artificial neural network strategy. Despite the limited data availability, our results achieve an accuracy of about 75% of correctly predicting the exact value of the glycation probability of an arginine-containing peptide without setting thresholds upon whether it is decided if a given arginine is modified or not. This contribution suggests a solution for predicting arginine glycation of short peptides.

Racial Discrimination and Alcohol Problems: Examining Interactions with Genetic Risk and Impulsivity among African American Young Adults.

Experiences of racial discrimination have been shown to increase risk for alcohol problems. Some individuals may be particularly vulnerable to the negative effects of racial discrimination. However, little research has examined interaction effects between racial discrimination and individual characteristics, such as genetic predispositions and personality, in relation to alcohol outcomes. This study examined whether genetic risk and dimensions of impulsivity moderate the association between racial discrimination and alcohol problems among African American young adults (n = 383, Mage = 20.65, SD = 2.28; 81% female). Participants completed online surveys and provided a saliva sample for genotyping. Results from multiple regression analyses indicated that both blatant and subtle forms of racial discrimination (i.e., experience of racist events and racial microaggressions) were associated with more alcohol problems. Racial microaggressions interacted with dimensions of impulsivity in relation to alcohol problems, such that racial microaggressions were associated with more alcohol problems when negative urgency was high or when sensation seeking was low. There was no significant interaction between alcohol use disorder genome-wide polygenic score and experience of racist events or racial microaggression in relation to alcohol problems, which may partly reflect low power due in part to limited representation of African-Americans in genetic research. The findings highlight the need to increase the representation of African Americans in genetically-informed research in order to better characterize genetic risk and understand gene-environment interaction in this understudied population, as well as the importance of examining impulsivity as a multidimensional construct that interacts with racial discrimination in relation to alcohol outcomes.

Cartilage Grafting Outcomes in Intermediate and Definitive Cleft Rhinoplasty.

OBJECTIVE: To compare cartilage grafting outcomes in intermediate versus definitive cleft rhinoplasty. DESIGN: A retrospective chart review was conducted. The χ2 and Fisher exact tests were used for statistical analyses. Results were considered statistically significant at P < .05. PARTICIPANTS: All subjects who underwent revision cleft rhinoplasties between July 2011 and June 2019 were included. Subjects with syndromic conditions were excluded. RESULTS: A total of 46 subjects with a cleft nose deformity underwent 65 rhinoplasty procedures. The ages averaged 17 years (range 5-50) with 34 (73.9%) males and 12 (26.1%) females. In the intermediate group, 6 (28.6%) subjects required cartilage grafting as part of 6 cleft rhinoplasties, whereas 15 (71.4%) subjects underwent a total of 26 cleft rhinoplasties that did not require grafting. In the definitive group, 18 (76%) subjects required cartilage grafting over 21 cleft rhinoplasties, whereas 7 (24%) subjects underwent a total of 9 cleft rhinoplasties where cartilage grafting was not required. The difference between the number of subjects requiring cartilage grafting in the intermediate versus the definitive group was statistically significant (P = .007). Ear concha and nose were the most frequently used cartilage donor sites, with no observed complications. CONCLUSIONS: Cartilage grafting was significantly more common in the definitive rhinoplasty group. Intermediate cleft rhinoplasty during the 5- to 13-year age period was effective, with a low-risk profile. In our experience, ear concha and nose were the preferred cartilage donor sites, with effective results and an excellent safety profile.

Fast CNN Stereo Depth Estimation through Embedded GPU Devices.

Current CNN-based stereo depth estimation models can barely run under real-time constraints on embedded graphic processing unit (GPU) devices. Moreover, state-of-the-art evaluations usually do not consider model optimization techniques, being that it is unknown what is the current potential on embedded GPU devices. In this work, we evaluate two state-of-the-art models on three different embedded GPU devices, with and without optimization methods, presenting performance results that illustrate the actual capabilities of embedded GPU devices for stereo depth estimation. More importantly, based on our evaluation, we propose the use of a U-Net like architecture for postprocessing the cost-volume, instead of a typical sequence of 3D convolutions, drastically augmenting the runtime speed of current models. In our experiments, we achieve real-time inference speed, in the range of 5-32 ms, for 1216 × 368 input stereo images on the Jetson TX2, Jetson Xavier, and Jetson Nano embedded devices.

SSD vs. YOLO for Detection of Outdoor Urban Advertising Panels under Multiple Variabilities.

This work compares Single Shot MultiBox Detector (SSD) and You Only Look Once (YOLO) deep neural networks for the outdoor advertisement panel detection problem by handling multiple and combined variabilities in the scenes. Publicity panel detection in images offers important advantages both in the real world as well as in the virtual one. For example, applications like Google Street View can be used for Internet publicity and when detecting these ads panels in images, it could be possible to replace the publicity appearing inside the panels by another from a funding company. In our experiments, both SSD and YOLO detectors have produced acceptable results under variable sizes of panels, illumination conditions, viewing perspectives, partial occlusion of panels, complex background and multiple panels in scenes. Due to the difficulty of finding annotated images for the considered problem, we created our own dataset for conducting the experiments. The major strength of the SSD model was the almost elimination of False Positive (FP) cases, situation that is preferable when the publicity contained inside the panel is analyzed after detecting them. On the other side, YOLO produced better panel localization results detecting a higher number of True Positive (TP) panels with a higher accuracy. Finally, a comparison of the two analyzed object detection models with different types of semantic segmentation networks and using the same evaluation metrics is also included.

Aetiology, diagnosis, and clinical management of vulvodynia.

Chronic vulvar pain or discomfort for which no obvious aetiology can be found, i.e. vulvodynia, can affect up to 16% of women, and it may be found in girls and women across all age groups and ethnicities. Most patients describe it as burning, stinging, irritation, or rawness. The symptoms may spread to the whole vulva (generalised vulvodynia) or only to part of it, such as the clitoris (clitorodynia) or the vestibule of the vagina (vestibulodynia). This condition is often underreported and underrecognised by health care providers. Vulvodynia is a significant burden to society, the health care system, the affected women, and their intimate partners. It has a negative impact on quality of life. Vulvodynia is a diagnosis of exclusion with unknown aetiology. The gynaecologist plays a key role in excluding other causes of vulvar pain, and collaborating with other health care providers to manage the patient's pain. Although many therapeutic options are available, such as vulvar care measures, psychological approaches, local treatment, oral medications, surgical procedures, electrical nerve stimulation, and laser therapy, there is no single treatment effective for all patients. That is why individualised management is needed. An individualised, holistic, and often multidisciplinary approach is needed to effectively manage the patient's pain and pain-related distress.

Uterine smooth muscle tumours of uncertain malignant potential: single-centre experience and review of the literature.

INTRODUCTION: Uterine smooth muscle tumours of uncertain malignant potential (STUMPs) are a rare histologically heterogeneous group of uterine smooth muscle tumours (SMTs). Their malignant potential and clinical differentiation between leiomyoma and leiomyosarcoma remain uncertain prior to surgical removal. AIM OF THE STUDY: To investigate the patients and tumour characteristics of patients with STUMPs and to propose algorithms for optimal diagnosis, treatment, and follow-up management. MATERIAL AND METHODS: This was a single-centre retrospective cohort study of all patients who underwent surgery for a preoperative diagnosis of uterine myoma at the University Hospital "Dr. Georgi Stranski", Pleven, Bulgaria during a period of 33 months (from January 2013 until October 2015). Data were obtained from the medical history records. We performed descriptive analysis to characterise the patient population (e.g. demographics, age, contraceptive use, and complaints that led to the diagnosis) and the tumour characteristics. Last data were obtained prior May 2019. RESULTS: A total of 320 medical records were retrospectively evaluated. The preoperative diagnosis of myoma was confirmed in 279 of the cases (89.4%). In 27 (8.3%) cases the final histological result was completely different. In 14 (2.3%) a histological postoperative diagnosis of STUMP was identified. All 14 STUMP lesions were intramural with a median size of 7.5 cm (range 3.5 to 15 cm). The median age at diagnosis of STUMP was 45.4 years (range 36 to 52 years), and 92.9% (n = 13) of the patients were premenopausal. Ultrasound data of a rapidly growing myoma were a reason for diagnosis in only three patients (25%), whereas 92.9% of the patients (n = 13) presented with heavy menstrual bleeding with or without anaemia. After surgery, none of the patients with STUMP experienced a relapse of the disease within the median follow-up time of 48 months (R = 40-78). CONCLUSIONS: STUMP tumours are rare tumours, predominantly diagnosed in premenopausal women. They define a group of patients with very good long-term prognosis. Therefore, longer follow-up is needed to allow for conclusions on recurrence rate and survival.