An examination of frontal asymmetry in relation to eating in the absence of hunger and loss-of-control eating.

Loss-of-control (LOC) eating involves a subjective feeling that one cannot stop eating or control one's eating. Individuals with LOC eating may exhibit strong appetitive drives and weak inhibitory control, and these two opposing motivations have been related to EEG measurements of frontal asymmetry or lateralized frontal activation. The present study investigated whether frontal asymmetry is related to hedonic hunger, LOC eating severity and frequency, and eating in the absence of hunger (EAH) in the laboratory. Fifty-nine individuals participated in an ostensible taste study after resting-state electroencephalogram (EEG) recordings. After the EEGs, they were provided a meal to eat until fullness, followed by an array of snacks and instructions to eat as much as they would like. The results indicated that several measures of right-frontal asymmetry were related to greater EAH and greater self-reported LOC eating severity. Although right-frontal asymmetry has been theorized to reflect avoidance motivation, recent evidence suggests it may indicate effortful control during approach-avoidance conflicts. Because individuals with LOC eating presumably experience heightened conflict between drives to eat beyond energy needs and to minimize such eating, those experiencing greater LOC may exert greater effort to manage these conflicting motivations. An integration of these neurobiological correlates of LOC eating may help provide a more comprehensive understanding of LOC eating and inform treatments.

Differential diagnosis of stage 2, 3 and 4 pressure injuries of the pelvis and lower extremity: a case series.

Constant, unrelieved pressure of local tissue, particularly over bony prominences, may provoke damage that progresses to necrosis and pressure injury (PI). Differentiating PIs from conditions of similar appearance is imperative to minimising complications and implementing prompt treatment. This case series describes several conditions that may be mistaken for a PI. Outlined are the key differences in patient history, presentation and clinical cues that assist in correctly identifying the true pathology behind these conditions. Conditions reviewed included: pyoderma gangrenosum; necrotising fasciitis; genital herpes; Marjolin ulcer, Rosai-Dorfman disease; vascular disease; coagulopathies; calciphylaxis; trauma and surgical wounds; pilonidal cysts; graft-versus-host disease; hidradenitis suppurativa; Stevens-Johnson syndrome; epidermolysis bullosa; radiation wounds; spider bites; and end-of-life skin failure pressure ulcers (also known as Kennedy ulcers). Although commonly recognised and diagnosed, stage 2, 3 and 4 PIs occasionally prove to be difficult to pinpoint, with undefined characteristics and similarities in presentation to several other conditions. Therefore, it is clinically vital to be aware of their appearance, risk factors and aetiology in order to make an appropriate patient assessment and avoid misdiagnosis.

Weight status is associated with clinical characteristics among individuals with bulimia nervosa.

Recent studies have found increasing rates of overweight and obesity in bulimia nervosa (BN). However, the relationships between body mass index (BMI) and BN symptoms and other clinically relevant constructs are unknown. Participants (N = 152 adults with BN) were assigned to three groups by BMI: group with no overweight or obesity (NOW-BN; BMI <25; N = 32), group with overweight (OW-BN; BMI ≥25 and <30; N = 66), and group with obesity (O-BN; BMI ≥30; N = 54). We compared the groups on demographics, diet and weight histories, body esteem, BN symptoms, and depression using chi square, analysis of variance, analysis of covariance, and Poisson regression models. The O-BN group was older (d = 0.57) and OW-BN and O-BN groups had greater proportions of race/ethnic minorities than NOW-BN group. The O-BN group was significantly younger at first diet (d = 0.41) and demonstrated significantly higher cognitive dietary restraint (d = 0.31). Compared to NOW-BN, O-BN participants had lower incidence of objective binge eating (incidence rate ratio [IRR] = 4.86) and driven exercise (IRR = 7.13), and greater incidence of vomiting (IRR = 9.30), laxative misuse (IRR = 4.01), and diuretic misuse (d = 2.08). O-BN participants also experienced higher shape (d = 0.41) and weight (d = 0.42) concerns than NOW-BN and OW-BN, although NOW-BN experienced higher shape (d = 0.44) and weight (d = 0.39) concerns than OW-BN. Groups did not differ on depression scores. These results were replicated when examining BMI as a continuous predictor across the full sample, with the exception of objective binge eating and driven exercise, which were not significantly associated with BMI. Individuals with BN and comorbid obesity have distinct clinical characteristics. Existing interventions may need to be adapted to meet clinical needs of these individuals.

The effect of weight suppression on eating behavior: Does the intentionality of weight loss matter?

Weight suppression (WS) has been consistently related to eating pathology. The weight loss that produces weight suppression has always been assumed to be intentional, but no study has tested whether unintentional weight loss would also be associated with eating pathology. The current study examined whether the association between WS and eating pathology may be moderated by intentionality of weight loss in a community-based sample of 520 adults. Participants were categorized into low WS (<5% weight loss from highest past weight), intentional, high WS (>5% intentional weight loss), and unintentional, high WS (>5% unintentional weight loss) groups. The intentional WS group reported greater restraint than the unintentional WS and low WS groups, and the low WS group reported greater restraint and more frequent loss-of-control (LOC) eating than those with unintentional WS. Further, WS was positively related to loss-of-control eating frequency only in the intentional WS group, and negatively associated with LOC eating frequency in the low WS group. Additionally, BMI was positively associated with LOC and binge eating frequency and restraint only in the low WS group. Given the relatively high prevalence of substantial but unintended weight loss found in this study, researchers studying weight suppression should consider asking about intentionality of weight loss and analyzing their data with and without unintentional weight suppressors included in the sample.

Correcting the reward imbalance in binge eating: A pilot randomized trial of reward re-training treatment.

Behavioral treatments for psychological disorders characterized by reward-driven maladaptive behaviors (e.g., substance use disorder, eating disorders, behavioral addictions) primarily seek to reduce hyper-reward response to disorder-specific stimuli. Suboptimal outcomes for these treatments highlight the need to also target hypo-reward response to day-to-day life activities. The present study sought to conduct an initial test of a novel behavioral treatment, Reward Re-Training (RRT) to target hyper- and hypo-reward response in individuals with binge eating. Individuals with binge eating (N = 23) were randomly assigned to either 10 weeks of outpatient, group-based RRT treatment or a waitlist control. RRT was found to be feasible and acceptable, demonstrated large impacts on both hypo- and hyper-reward response (measured by self-report (pre-to post-treatment ηp2 range 0.38-0.58) and neural activation via fMRI), and was efficacious in reducing eating disorder pathology (ηp2 range 0.40-0.64, including binge eating, ηp2 = 0.64) compared to waitlist control (ηp2 range 0.00-0.04). This pilot data provides preliminary support for the feasibility, acceptability, and effectiveness of a novel treatment targeting reward imbalance for individuals with binge eating. Future evaluations of RRT may benefit from an active treatment comparison condition and a follow-up assessment to examine persistence of positive outcomes.

Evaluating the use of lamotrigine to reduce mood lability and impulsive behaviors in adults with chronic and severe eating disorders.

BACKGROUND: Gold-standard psychological and pharmacological treatments for bulimic-spectrum eating disorders only result in remission for around 50% of patients; patients with affective lability and impulsivity represent a subgroup with particularly poor outcomes. Both dialectical behavior therapy (DBT), a treatment for emotion dysregulation, and lamotrigine, a mood stabilizer, have demonstrated promise for targeting affective lability and impulsivity; however, data exploring the combination of these interventions remain limited. OBJECTIVE: We followed a group of women with recurrent dysregulated eating behaviors (N = 62) throughout intensive DBT treatment and compared the symptom trajectory of those prescribed lamotrigine (n = 28) and those who were not (n = 34). METHOD: Participants completed surveys every 2 weeks throughout treatment. RESULTS: Group analyses suggested that all participants self-reported decreases in emotional reactivity, negative urgency, and symptoms of borderline personality disorder (BPD). The lamotrigine group reported greater elevations in BPD symptoms at baseline, but demonstrated steeper decreases in emotion and behavioral dysregulation than the non-matched comparison group. Within-subject analyses suggested that within the lamotrigine group, subjects reported greater decreases in symptoms following prescription of lamotrigine. CONCLUSIONS: Findings provide initial data suggesting that lamotrigine could be useful as an adjunctive treatment for patients with affective lability and impulsivity. LEVEL OF EVIDENCE: IV, time series without randomization.

Changes in cognitive and behavioral control after lamotrigine and intensive dialectical behavioral therapy for severe, multi-impulsive bulimia nervosa: an fMRI case study.

PURPOSE: Adults with bulimia nervosa (BN) and co-occurring emotional dysregulation and multiple impulsive behaviors are less responsive to existing interventions. Initial data suggest that the combination of Dialectical Behavior Therapy (DBT) and a mood stabilizer, lamotrigine, significantly reduces symptoms of affective and behavioral dysregulation in these patients. Identifying candidate neurobiological mechanisms of change for this novel treatment combination may help guide future randomized controlled trials and inform new and targeted treatment development. Here, we examined neurocognitive and symptom changes in a female patient with BN and severe affective and behavioral dysregulation who received DBT and lamotrigine. METHODS: Go/no-go task performance data and resting-state functional MRI scans were acquired before the initiation of lamotrigine (after 6 weeks in an intensive DBT program), and again after reaching and maintaining a stable dose of lamotrigine. The patient completed a battery of symptom measures biweekly for 18 weeks over the course of treatment. RESULTS: After lamotrigine initiation, the patient made fewer errors on a response inhibition task and showed increased and new connectivity within frontoparietal and frontolimbic networks involved in behavioral and affective control. Accompanying this symptom improvement, the patient reported marked reductions in bulimic symptoms, behavioral dysregulation, and reactivity to negative affect, along with increases in DBT skills use. CONCLUSION: Improved response inhibition and cognitive control network connectivity should be further investigated as neurocognitive mechanisms of change with combined DBT and lamotrigine for eating disorders. Longitudinal, controlled trials integrating neuroimaging and symptom measures are needed to fully evaluate the effects of this treatment. LEVEL OF EVIDENCE: IV: Evidence obtained from multiple time series with or without the intervention, such as case studies.

Within-subject weight variability in bulimia nervosa: Correlates and consequences.

OBJECTIVE: The oscillations between binge eating, purging, and dieting in bulimia nervosa (BN) may produce substantial within-subject weight variability. Although weight variability has been predictive of eating- and weight-related variables in community samples, it has not been empirically examined in eating disorders. The current study examined cross-sectional and prospective associations between weight variability and BN pathology. METHOD: Four weights were collected over an average of 42.02 days, and weight variability was calculated as the root mean square error around each individual's weight trajectory regression line. Linear regressions were performed to examine the association between weight variability and eating disorder psychopathology, cross-sectionally at baseline and prospectively at 6-month follow-up, adjusting for baseline BMI. RESULTS: Weight variability was cross-sectionally associated with eating pathology, but these relationships became non-significant after adjusting for BMI. However, at 6-month follow-up, greater baseline weight variability predicted increases in body dissatisfaction, shape and weight concerns, and global eating pathology, even after adjusting for baseline BMI. DISCUSSION: These findings demonstrate, for the first time, that within-subject weight variability predicts greater eating disorder pathology over time in BN. The results add to evidence that weight history variables contribute to BN psychopathology above and beyond well-documented psychological dysfunction in BN.

Associations of elevated weight status with symptom severity and treatment outcomes in binge/purge eating disorders.

OBJECTIVE: Binge-eating and purging behaviors commonly co-occur with overweight. However, little is known about the potential associations of elevated weight status with eating disorder severity or treatment outcomes. Thus, the present study compared binge-eating and purging patients with low, normal, and high weight statuses on eating disorder and mood symptoms at treatment admission, and tested whether weight status was associated with symptom change over treatment. METHOD: The sample included 135 adult female patients in an intensive outpatient program, who completed self-assessments at admission and discharge. MANOVAs compared the groups at treatment admission, and multilevel models examined changes over time. RESULTS: At admission, the high-weight group reported greater fasting frequency than the normal-weight group, and higher shape and weight concerns than the low-weight group. Over time, the high-weight group additionally showed higher eating disorder psychological symptom severity than the normal-weight group. The groups did not differ on mood symptoms at admission. Longitudinal results indicated that the groups showed comparable symptom improvements over treatment. DISCUSSION: These findings highlight the severity of higher-weight patients with bulimia nervosa. Additionally, although these patients may present with more severe symptoms, their response to an intensive treatment may be comparable to that of normal- or lower-weight groups.

Short Total Synthesis of [15N5]-Cylindrospermopsins from 15NH4Cl Enables Precise Quantification of Freshwater Cyanobacterial Contamination.

Fresh water cyanobacterial algal blooms represent a major health risk because these organisms produce cylindrospermopsin, a toxic, structurally complex, zwitterionic uracil-guanidine alkaloid recognized by the EPA as a dangerous drinking water contaminant. At present, the ability to detect and quantify the presence of cylindrospermospin in water samples is severely hampered by the lack of an isotopically labeled standard for analytical mass spectrometry. Herein, we present a concise, scaled total synthesis of 15N cylindrospermosin from 15N ammonium chloride, which leverages a unique stereoselective intramolecular double conjugate addition step to assemble the tricyclic guanidine core. In addition to providing the first pure isotopically labeled probe for precise quantification of this potent biotoxin in fresh water sources, our results demonstrate how unique constraints associated with isotope incorporation compel novel solutions to synthesis design.

SBOL Visual: A Graphical Language for Genetic Designs.

Synthetic Biology Open Language (SBOL) Visual is a graphical standard for genetic engineering. It consists of symbols representing DNA subsequences, including regulatory elements and DNA assembly features. These symbols can be used to draw illustrations for communication and instruction, and as image assets for computer-aided design. SBOL Visual is a community standard, freely available for personal, academic, and commercial use (Creative Commons CC0 license). We provide prototypical symbol images that have been used in scientific publications and software tools. We encourage users to use and modify them freely, and to join the SBOL Visual community: http://www.sbolstandard.org/visual.

Design, implementation and practice of JBEI-ICE: an open source biological part registry platform and tools.

The Joint BioEnergy Institute Inventory of Composable Elements (JBEI-ICEs) is an open source registry platform for managing information about biological parts. It is capable of recording information about 'legacy' parts, such as plasmids, microbial host strains and Arabidopsis seeds, as well as DNA parts in various assembly standards. ICE is built on the idea of a web of registries and thus provides strong support for distributed interconnected use. The information deposited in an ICE installation instance is accessible both via a web browser and through the web application programming interfaces, which allows automated access to parts via third-party programs. JBEI-ICE includes several useful web browser-based graphical applications for sequence annotation, manipulation and analysis that are also open source. As with open source software, users are encouraged to install, use and customize JBEI-ICE and its components for their particular purposes. As a web application programming interface, ICE provides well-developed parts storage functionality for other synthetic biology software projects. A public instance is available at public-registry.jbei.org, where users can try out features, upload parts or simply use it for their projects. The ICE software suite is available via Google Code, a hosting site for community-driven open source projects.

Decarboxylative C-N Coupling of 2,2-Difluorobicyclo[1.1.1]pentane (BCP-F2) Building Blocks.

Described herein is our effort toward achieving the decarboxylative functionalization of 2,2-difluorobicyclo[1.1.1]pentane (BCP-F2) building blocks. When compared with the nonfluorinated bicyclo[1.1.1]pentane (BCP) analogues, we discovered divergent reactivities. This is the first successful decarboxylative coupling of BCP-F2 building blocks reported via the photoredox mechanism.

Characterizing Asian American medical students' experiences with microaggression and the impact on their well-being.

PURPOSE: This mixed-methods study quantified and characterized incidents of microaggressions experienced by Asian American medical students. The authors report on their impact and suggest improvements to create a more equitable and supportive learning environment. METHOD: Quantitative and qualitative data were collected from 305 participants who self-identified as Asian American or Pacific Islander. An online, anonymous survey was sent to US medical students through the Asian Pacific American Medical Student Association (APAMSA). Questions explored incidence, characteristics of, and response to microaggressions. We conducted four focus groups to further characterize students' experiences. Data were organized and coded, and thematic analysis was used to identify core themes. RESULTS: Racial microaggressions were prevalent among Asian American medical students. Nearly 70% (n = 213) of survey respondents reported experiencing at least one incident during their medical training to date. The most common perpetrators were patients (n = 151, 70.9%) and fellow medical students (n = 126, 59.2%), followed by professors (n = 90, 42.3%). The most prevalent themes included being perceived as a perpetual foreigner, the assumption of timidness, and ascription of the model minority myth. Students rarely reported the incident and usually did not respond immediately due to fear of retaliation, uncertainties about the experience or how to respond appropriately, and perception that they would bear the burden of advocacy alone. Experiences with microaggressions led to feelings of frustration and burnout and had a negative impact on mental health. Recommendations were made to improve the anonymous reporting systems in medical schools, and to increase diversity and inclusion in medical education and leadership. CONCLUSIONS: Asian American medical students face high exposure to racial microaggressions during their medical education that adversely impact their mental health. Changes are needed in medical training to create a more equitable and inclusive learning environment.

Distraction Osteogenesis for Frontosphenoidal Craniosynostosis: a Novel Surgical Treatment Modality of a Rare Suture Fusion.

Frontosphenoidal craniosynostosis (FSC) is a rare premature fusion of the frontosphenoidal suture that results in anterior plagiocephaly. When associated with severe cranial deformity, surgical treatment is beneficial. All previously reported cases of FSC correction have utilized fronto-orbital remodeling and advancement to achieve improved anatomy and increased intracranial volume. For patients with isolated synostosis deformities, we believe that distraction osteogenesis can be a viable option, with the additional benefit of quicker operating time, shorter hospital stays, and less irregularity in final head contour. This case illustrates the feasibility of using distraction osteogenesis in the management of FSC.

Pediatric Mandibular Fracture Management: Intraoperative Thermoplastic Splint Fabrication and Circummandibular Wires, without Maxillomandibular Fixation.

Management of mandibular fractures often involves the use of maxillomandibular fixation (MMF) to attain immobility of the fractured segments. This can be used as a primary treatment modality or as an adjunct in fracture management. This technique, however, has its drawbacks due to the great burden of care imposed on patients. In the following case, fixation of a pediatric open mandibular body fracture was attained without the use of MMF, and bone union was achieved. Due to age, safety concerns, long-distance travel, and parent's preference, the routine management of this type of fracture with MMF using piriform aperture drop wires and circummandibular wires was not done. Instead, the fracture was reduced, and an intraoral mandibular impression was taken in the operating room, which was used to create a stone model. A 2-mm acrylic splint was designed and fabricated from the stone model, and two circummandibular wires were placed. The wires were tightened over the acrylic splint to achieve stabilization of the mandibular reduction. At 4 weeks postoperatively, the splint was removed, and the patient was maintained on a soft diet. At 6 weeks, bone union was appreciated clinically by immobility of the mandibular segments, and the patient was advanced to a regular diet. Occlusion was corrected to premorbid state by clinical findings and 6 months postoperative imaging. This technique represents an effective approach in managing pediatric mandibular fractures when MMF cannot be used.

Modifications to the WHISTLE Flap Procedure for Correction of Secondary Cleft Lip Deformities.

Background: The whistle deformity, a deficiency of tissue in the central upper lip, is a consequential outcome of primary cleft lip repair. Among multiple described reconstructive options, the wide-hinged island swing transposition labial enhancement (WHISTLE) flap procedure by Grewal et al has been shown to be a reliable technique that restores the continuity of the orbicularis oris muscle and creates a more natural appearing tubercle and central lip element. This article aims to refine the WHISTLE flap procedure with the addition of tailored mucomuscular flaps and an upper lip-lengthening mucosal Z-plasty. Methods: A total of 11 patients with a whistle deformity were examined. All underwent the WHISTLE flap procedure with tailored mucomuscular flaps and a mucosal Z-plasty. The patients were followed for a period of from 6 to 51.5 months. Pre- and postoperative photographs were used for objective outcome comparison. Results: From 2018 to 2023, a total of 11 patients with a whistle deformity were included in the final cohort, comprised four bilateral and seven unilateral cleft lips. Ten cases (90.1%) resulted in satisfactory postoperative cosmetic appearance and did not require further interventions. A single patient with a significant preoperative discrepancy between the upper and lower lip volumes had a postoperative residual deformity. None of the patients demonstrated any functional deficits associated with the procedure. Conclusions: The WHISTLE flap procedure with the proposed individual tailoring of the mucomuscular flap and Z-plasty for mucosal scar lengthening has excellent cosmetic outcomes and can be considered as the primary treatment modality in most patients with a whistle deformity.

Validation of a machine learning technique for segmentation and pose estimation in single plane fluoroscopy.

Kinematics of total knee replacements (TKR) play an important role in assessing the success of a procedure and would be a valuable addition to clinical practice; however, measuring TKR kinematics is time consuming and labour intensive. Recently, an automatic single-plane fluoroscopic method utilizing machine learning has been developed to facilitate a quick and simple process for measuring TKR kinematics. This study aimed to validate the new automatic single-plane technique using biplanar radiostereometric analysis (RSA) as the gold standard. Twenty-four knees were imaged at various angles of flexion in a dedicated RSA lab and 113 image pairs were obtained. Only the lateral RSA images were used for the automatic single-plane technique to simulate single-plane fluoroscopy. Two networks helped automate the kinematics measurement process, one segmented implant components and the other generated an initial pose estimate for the optimization algorithm. Kinematics obtained via the automatic single plane and manual biplane techniques were compared using root-mean-square error and Bland-Altman plots. Two observers measured the kinematics using the automated technique and results were compared with assess reproducibility. Root-mean-square errors were 0.8 mm for anterior-posterior translation, 0.5 mm for superior-inferior translation, 2.6 mm for medial-lateral translation, 1.0° for flexion-extension, 1.2° for abduction-adduction, and 1.7° for internal-external rotation. Reproducibility, reported as root-mean-square errors between operator measurements, was submillimeter for in-plane translations and below 2° for all rotations. Clinical Significance: The advantages of the automated single plane technique should aid in the kinematic measurement process and help researchers and clinicians perform TKR kinematic analyses.

Impaired belief updating and devaluation in adult women with bulimia nervosa.

Recent models of bulimia nervosa (BN) propose that binge-purge episodes ultimately become automatic in response to cues and insensitive to negative outcomes. Here, we examined whether women with BN show alterations in instrumental learning and devaluation sensitivity using traditional and computational modeling analyses of behavioral data. Adult women with BN (n = 30) and group-matched healthy controls (n = 31) completed a task in which they first learned stimulus-response-outcome associations. Then, participants were required to repeatedly adjust their responses in a "baseline test", when different sets of stimuli were explicitly devalued, and in a "slips-of-action test", when outcomes instead of stimuli were devalued. The BN group showed intact behavioral sensitivity to outcome devaluation during the slips-of-action test, but showed difficulty overriding previously learned stimulus-response associations on the baseline test. Results from a Bayesian learner model indicated that this impaired performance could be accounted for by a slower pace of belief updating when a new set of previously learned responses had to be inhibited (p = 0.036). Worse performance and a slower belief update in the baseline test were each associated with more frequent binge eating (p = 0.012) and purging (p = 0.002). Our findings suggest that BN diagnosis and severity are associated with deficits in flexibly updating beliefs to withhold previously learned responses to cues. Additional research is needed to determine whether this impaired ability to adjust behavior is responsible for maintaining automatic and persistent binge eating and purging in response to internal and environmental cues.

mTOR supports long-term self-renewal and suppresses mesoderm and endoderm activities of human embryonic stem cells.

Despite the recent identification of the transcriptional regulatory circuitry involving SOX2, NANOG, and OCT-4, the intracellular signaling networks that control pluripotency of human embryonic stem cells (hESCs) remain largely undefined. Here, we demonstrate an essential role for the serine/threonine protein kinase mammalian target of rapamycin (mTOR) in regulating hESC long-term undifferentiated growth. Inhibition of mTOR impairs pluripotency, prevents cell proliferation, and enhances mesoderm and endoderm activities in hESCs. At the molecular level, mTOR integrates signals from extrinsic pluripotency-supporting factors and represses the transcriptional activities of a subset of developmental and growth-inhibitory genes, as revealed by genome-wide microarray analyses. Repression of the developmental genes by mTOR is necessary for the maintenance of hESC pluripotency. These results uncover a novel signaling mechanism by which mTOR controls fate decisions in hESCs. Our findings may contribute to effective strategies for tissue repair and regeneration.