'I'm a failure again, I can't do it': Attitudes towards, and experiences of, exercise participation in adults with class III obesity.

OBJECTIVES: Living within a larger body brings unique challenges to exercise participation, which are poorly understood. This qualitative study explored the attitudes towards, and experiences of, exercise participation in adults with class III obesity. DESIGN: Individual semi-structured qualitative interviews. METHODS: We recruited 30 adults with class III obesity (body mass index: 45.8 ± 8.6 kg/m2) from a specialist multidisciplinary weight management service. Participants took part in semi-structured interviews while participating in a 6-month home-based aerobic and resistance exercise intervention. Open-ended questions were used flexibly to explore their views and experiences of exercise, encompassing barriers, motives and perceived benefits. Transcripts were analysed using reflexive thematic analysis. RESULTS: Three themes were developed: (1) a web of barriers; (2) tailored exercise facilitates positive experiences; and (3) a desire to live a normal life. People with class III obesity perceived that they were unable to do exercise; a view that was attributed to perceived judgement, low physical function, pain during everyday activities and failed weight loss attempts. These complex physical and psychosocial barriers to exercise were described as contributing to exercise avoidance. High value was placed on tailored exercise that accommodates the unique needs of moving in a larger body. A desire to carry out everyday tasks underpinned motivations for exercise. CONCLUSIONS: Our findings suggest that multi-component obesity interventions should move away from generic exercise prescriptions designed to maximize energy expenditure, and instead move towards addressing the unique physical and psychosocial needs of people who have class III obesity with tailored person-centred and weight-neutral exercise prescriptions.

Efficacy and Safety of Dapagliflozin in Patients With Acute Heart Failure.

BACKGROUND: The primary goals during acute heart failure (AHF) hospitalization are decongestion and guideline-directed medical therapy (GDMT) optimization. Unlike diuretics or other GDMT, early dapagliflozin initiation could achieve both AHF goals. OBJECTIVES: The authors aimed to assess the diuretic efficacy and safety of early dapagliflozin initiation in AHF. METHODS: In a multicenter, open-label study, 240 patients were randomized within 24 hours of hospital presentation for hypervolemic AHF to dapagliflozin 10 mg once daily or structured usual care with protocolized diuretic titration until day 5 or hospital discharge. The primary outcome, diuretic efficiency expressed as cumulative weight change per cumulative loop diuretic dose, was compared across treatment assignment using a proportional odds model adjusted for baseline weight. Secondary and safety outcomes were adjudicated by a blinded committee. RESULTS: For diuretic efficiency, there was no difference between dapagliflozin and usual care (OR: 0.65; 95% CI: 0.41-1.02; P = 0.06). Dapagliflozin was associated with reduced loop diuretic doses (560 mg [Q1-Q3: 260-1,150 mg] vs 800 mg [Q1-Q3: 380-1,715 mg]; P = 0.006) and fewer intravenous diuretic up-titrations (P ≤ 0.05) to achieve equivalent weight loss as usual care. Early dapagliflozin initiation did not increase diabetic, renal, or cardiovascular safety events. Dapagliflozin was associated with improved median 24-hour natriuresis (P = 0.03) and urine output (P = 0.005), expediting hospital discharge over the study period. CONCLUSIONS: Early dapagliflozin during AHF hospitalization is safe and fulfills a component of GDMT optimization. Dapagliflozin was not associated with a statistically significant reduction in weight-based diuretic efficiency but was associated with evidence for enhanced diuresis among patients with AHF. (Efficacy and Safety of Dapagliflozin in Acute Heart Failure [DICTATE-AHF]; NCT04298229).

'I've learned a lot about myself this year': Young student women's perceptions of their cumulative use of digital fitness technologies across the Covid-19 pandemic.

Many young women turned to digital fitness technologies (DFT) to support their health and wellbeing during the covid-19 pandemic. The present study explores young student women's retrospective perceptions of their cumulative engagement with DFT, across periods of restriction and easing (March 2020-2021). Seventeen UK-based women (Age M = 20.29, SD = 1.72); Ethnicity White = 94.12% participated in one-on-one interviews using an adapted scroll-back technique. Data was analysed using narrative-informed reflexive thematic analysis. Three themes were developed: My lockdown #fitnesstransformation: DFT as information and inspiration, My unrealistic expectations: DFT as a source of comparison and concern and My new body positive and resilient self: DFT as a catalyst to self-development. Themes highlight how perceptions of DFT changed over time as a consequence of repeat engagement, sociocultural context and psychological meaning-making. Crucially, findings underscore the importance of examining the collective and cumulative effects of DFT engagement on health and wellbeing, both positive and negative.

Molecular discoveries in microbial DMSP synthesis.

Dimethylsulfoniopropionate (DMSP) is one of the Earth's most abundant organosulfur compounds because many marine algae, bacteria, corals and some plants produce it to high mM intracellular concentrations. In these organisms, DMSP acts an anti-stress molecule with purported roles to protect against salinity, temperature, oxidative stress and hydrostatic pressure, amongst many other reported functions. However, DMSP is best known for being a major precursor of the climate-active gases and signalling molecules dimethylsulfide (DMS), methanethiol (MeSH) and, potentially, methane, through microbial DMSP catabolism. DMSP catabolism has been extensively studied and the microbes, pathways and enzymes involved have largely been elucidated through the application of molecular research over the last 17 years. In contrast, the molecular biology of DMSP synthesis is a much newer field, with the first DMSP synthesis enzymes only being identified in the last 5 years. In this review, we discuss how the elucidation of key DMSP synthesis enzymes has greatly expanded our knowledge of the diversity of DMSP-producing organisms, the pathways used, and what environmental factors regulate production, as well as to inform on the physiological roles of DMSP. Importantly, the identification of key DMSP synthesis enzymes in the major groups of DMSP producers has allowed scientists to study the distribution and predict the importance of different DMSP-producing organisms to global DMSP production in diverse marine and sediment environments. Finally, we highlight key challenges for future molecular research into DMSP synthesis that need addressing to better understand the cycling of this important marine organosulfur compound, and its magnitude in the environment.

Clinical outcomes of de novo metastatic HER2-positive inflammatory breast cancer.

Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer that presents as de novo metastatic disease in 20-30% of cases, with one-third of cases demonstrating HER2-positivity. There has been limited investigation into locoregional therapy utilization following HER2-directed systemic therapy for these patients, and their locoregional progression or recurrence (LRPR) and survival outcomes. Patients with de novo HER2-positive metastatic IBC (mIBC) were identified from an IRB-approved IBC registry at Dana-Farber Cancer Institute. Clinical, pathology, and treatment data were abstracted. Rates of LRPR, progression-free survival (PFS), overall survival (OS), and pathologic complete response (pCR) were determined. Seventy-eight patients diagnosed between 1998 and 2019 were identified. First-line systemic therapy comprised chemotherapy for most patients (97.4%) and HER2-directed therapy for all patients (trastuzumab [47.4%]; trastuzumab+pertuzumab [51.3%]; or trastuzumab emtansine [1.3%]). At a median follow-up of 2.7 years, the median PFS was 1.0 year, and the median OS was 4.6 years. The 1- and 2-year cumulative incidence of LRPR was 20.7% and 29.0%, respectively. Mastectomy was performed after systemic therapy in 41/78 patients (52.6%); 10 had a pCR (24.4%) and all were alive at last follow-up (1.3-8.9 years after surgery). Among 56 patients who were alive and LRPR-free at one year, 10 developed LRPR (surgery group = 1; no-surgery group = 9). In conclusion, patients with de novo HER2-positive mIBC who undergo surgery have favorable outcomes. More than half of patients received systemic and local therapy with good locoregional control and prolonged survival, suggesting a potential role for local therapy.

Iron Deficiency in Heart Failure: A Scientific Statement from the Heart Failure Society of America.

Iron deficiency is present in approximately 50% of patients with symptomatic heart failure and is independently associated with worse functional capacity, lower quality of, life and increased mortality. The purpose of this document is to summarize current knowledge of how iron deficiency is defined in heart failure and its epidemiology and pathophysiology, as well as pharmacological considerations for repletion strategies. This document also summarizes the rapidly expanding array of clinical trial evidence informing when, how, and in whom to consider iron repletion.

Copy Number Variation in Inflammatory Breast Cancer.

Identification of a unique genomic biomarker in de novo inflammatory breast cancer (IBC) may provide an insight into the biology of this aggressive disease. The goal of our study was to elucidate biomarkers associated with IBC. We examined breast biopsies collected from Dana-Farber Cancer Institute patients with IBC prior to initiating preoperative systemic treatment (30 samples were examined, of which 14 were eligible). Patients without available biopsies (n = 1), with insufficient tumor epithelial cells (n = 10), or insufficient DNA yield (n = 5) were excluded from the analysis. Molecular subtype and tumor grade were abstracted from a medical records' review. Ten IBC tumors were estrogen-receptor-positive (ER+) and human epidermal growth factor receptor 2 (HER2)-negative (n = 10 out of 14). Sufficient RNA and DNA were simultaneously extracted from 14 biopsy specimens using the Qiagen AllPrep Kit. RNA was amplified using the Sensation kit and profiled using the Affymetrix Human Transcriptome Array 2.0. DNA was profiled for genome-wide copy number variation (CNV) using the Affymetrix OncoScan Array and analyzed using the Nexus Chromosome Analysis Suite. Among the 14 eligible samples, we first confirmed biological concordance and quality control metrics using replicates and gene expression data. Second, we examined CNVs and gene expression change by IBC subtype. We identified significant CNVs in IBC patients after adjusting for multiple comparisons. Next, to assess whether the CNVs were unique to IBC, we compared the IBC CNV data to fresh-frozen non-IBC CNV data from The Cancer Genome Atlas (n = 388). On chromosome 7p11.2, we identified significant CN gain located at position 58,019,983-58,025,423 in 8 ER+ IBC samples compared to 338 non-IBC ER+ samples (region length: 5440 bp gain and 69,039 bp, False Discovery Rate (FDR) p-value = 3.12 × 10-10) and at position 57,950,944-58,025,423 in 3 TN-IBC samples compared to 50 non-IBC TN samples (74,479 base pair, gain, FDR p-value = 4.27 × 10-5; near the EGFR gene). We also observed significant CN loss on chromosome 21, located at position 9,648,315-9,764,385 (p-value = 4.27 × 10-5). Secondarily, differential gene expression in IBC patients with 7p11.2 CN gain compared to SUM149 were explored after FDR correction for multiple testing (p-value = 0.0016), but the results should be interpreted with caution due to the small sample size. Finally, the data presented are hypothesis-generating. Validation of CNVs that contribute to the unique presentation and biological features associated with IBC in larger datasets may lead to the optimization of treatment strategies.

TRPS1 expression is sensitive and specific for primary extramammary Paget disease.

AIMS: Extramammary Paget disease (EMPD) is an epithelial neoplasm that can occur at many sites, including the vulva and scrotum. EMPD is characterised by the presence of neoplastic cells, in single cells and clusters, that infiltrate all layers of non-neoplastic squamous epithelium. The differential diagnosis for EMPD includes melanoma in situ and secondary involvement of tumours from other sites, such as urothelial or cervical; pagetoid spread of tumor cells can also been seen at other sites, such as anorectal mucosa. The most frequently utilised biomarkers for confirming the diagnosis of EMPD include CK7 and GATA3; however, these biomarkers lack specificity. The purpose of this study was to evaluate TRPS1, a newly described breast biomarker, in pagetoid neoplasms of the vulva, scrotum and anorectum. METHODS AND RESULTS: Fifteen cases of primary EMPD of the vulva (two with associated invasive carcinoma) and four primary EMPD of the scrotum showed strong nuclear immunoreactivity for TRPS1. In contrast, five cases of vulvar melanoma in situ, one case of urothelial carcinoma with secondary pagetoid spread into the vulva and two anorectal adenocarcinomas with pagetoid spread into anal skin (one with associated invasive carcinoma) were negative for TRPS1. Additionally, weak nuclear TRPS1 staining was observed in non-neoplastic tissues (e.g. keratinocytes), but always with less intensity when compared to tumour cells. CONCLUSIONS: These results demonstrate that TRPS1 is a sensitive and specific biomarker for EMPD, and may be especially useful for excluding secondary involvement of the vulva by urothelial and anorectal carcinomas.

HER2-low inflammatory breast cancer: Clinicopathologic features and prognostic implications.

BACKGROUND: HER2)-low expression is a predictive biomarker for novel anti-HER2 antibody-drug conjugates. However, little is known about its clinical significance in inflammatory breast cancer (IBC). METHODS: Patients diagnosed with HER2-negative IBC between December 1999 and December 2020 were identified from the Dana-Farber Cancer Institute IBC registry. Patients were divided into HER2-low (IHC 1+ or 2+/ISH-) and HER2-zero (IHC 0), comparing clinicopathologic features and disease outcomes between the two subgroups. RESULTS: The study included 276 patients. Among patients with stage III (n = 209) and stage IV (n = 67) IBC, 54% and 39% had HER2-low tumours, respectively. Oestrogen receptor (ER)-expressing tumours were more common in patients with HER2-low versus HER2-zero stage III IBC (65% versus 38%, p < 0.01). Among stage III patients undergoing surgery (n = 182), pathologic complete response (pCR) rates were higher for HER2-zero versus HER2-low IBC (11% versus 6%, OR: 1.8, 95%CI:0.6-5.3), but minimal differences persisted when separately analysing pCR by ER status. Similar invasive disease-free survival (iDFS) outcomes were observed among ER-positive HER2-zero versus HER2-low IBC (48-month iDFS: 63% versus 63%, HR: 1.10, 95%CI:0.57-2.13) and ER-negative HER2-zero versus HER2-low IBC (48-month iDFS: 28% versus 25%, HR: 1.19, 95%CI:0.69-2.04). Differences in overall survival (OS) were small, both among ER-positive HER2-zero versus HER2-low IBC (48-month OS: 80% versus 81%, HR: 0.82, 95%CI:0.39-1.73) and ER-negative HER2-zero versus HER2-low IBC (48-month OS: 34% versus 47%, HR: 1.34, 95%CI: 0.74-2.41). CONCLUSIONS: Marginal differences in clinicopathologic features and outcomes were observed in HER2-low versus HER2-zero IBC when controlling for ER status, not supporting the definition of HER2-low as a distinct subtype of IBC.

Early on-treatment transcriptional profiling as a tool for improving pathological response prediction in HER2-positive inflammatory breast cancer.

Background: Inflammatory breast cancer (IBC) is a rare and understudied disease, with 40% of cases presenting with human epidermal growth factor receptor 2 (HER2)-positive subtype. The goals of this study were to (i) assess the pathologic complete response (pCR) rate of short-term neoadjuvant dual-HER2-blockade and paclitaxel, (ii) contrast baseline and on-treatment transcriptional profiles of IBC tumor biopsies associated with pCR, and (iii) identify biological pathways that may explain the effect of neoadjuvant therapy on tumor response. Patients and Methods: A single-arm phase II trial of neoadjuvant trastuzumab (H), pertuzumab (P), and paclitaxel for 16 weeks was completed among patients with newly diagnosed HER2-positive IBC. Fresh-frozen tumor biopsies were obtained pretreatment (D1) and 8 days later (D8), following a single dose of HP, prior to adding paclitaxel. We performed RNA-sequencing on D1 and D8 tumor biopsies, identified genes associated with pCR using differential gene expression analysis, identified pathways associated with pCR using gene set enrichment and gene expression deconvolution methods, and compared the pCR predictive value of principal components derived from gene expression profiles by calculating and area under the curve for D1 and D8 subsets. Results: Twenty-three participants were enrolled, of whom 21 completed surgery following neoadjuvant therapy. Paired longitudinal fresh-frozen tumor samples (D1 and D8) were obtained from all patients. Among the 21 patients who underwent surgery, the pCR and the 4-year disease-free survival were 48% (90% CI 0.29-0.67) and 90% (95% CI 66-97%), respectively. The transcriptional profile of D8 biopsies was found to be more predictive of pCR (AUC = 0.91, 95% CI: 0.7993-1) than the D1 biopsies (AUC = 0.79, 95% CI: 0.5905-0.9822). Conclusions: In patients with HER2-positive IBC treated with neoadjuvant HP and paclitaxel for 16 weeks, gene expression patterns of tumor biopsies measured 1 week after treatment initiation not only offered different biological information but importantly served as a better predictor of pCR than baseline transcriptional analysis. Trial Registration: ClinicalTrials.gov identifier: NCT01796197 (https://clinicaltrials.gov/ct2/show/NCT01796197); registered on February 21, 2013.

Presence of Non-classic LCIS Is Not a Contraindication to Breast Conservation in Patients with Concomitant Invasive Breast Cancer or DCIS.

BACKGROUND: Non-classic lobular carcinoma in situ (NC-LCIS) represents a spectrum of lesions, histologically distinct from classic LCIS (C-LCIS) and ductal carcinoma in situ (DCIS). Several studies have reported on the safety of breast conservation (BCS) in patients with DCIS or invasive breast cancer and concomitant C-LCIS, yet there are no data addressing this question for patients with concomitant NC-LCIS. We evaluated local recurrence (LR) after BCS in patients with DCIS or invasive cancer and concomitant NC-LCIS. PATIENTS AND METHODS: We searched institutional databases using natural language processing to identify patients with DCIS or invasive breast cancer and concomitant NC-LCIS treated with BCS between 2000 and 2015. Charts were reviewed to collect demographics, disease and treatment details, and recurrence events. All results represent descriptive analyses. RESULTS: We identified 71 patients with DCIS (n = 13) or invasive cancer (n = 58) and concomitant NC-LCIS treated with BCS. Median patient age was 59 years (33-77 years), and median invasive tumor size was 1.2 cm (0.1-6.9 cm); 62% of DCIS and 79% of invasive cancer patients had hormone receptor (HR)-positive disease. Among DCIS patients, seven (54%) received radiation and none hormonal therapy. Among those with invasive cancer, 52 (90%) received radiation, 17 (29%) received chemotherapy and 44 of 55 with HR-positive disease (78%) received hormonal therapy. At median follow-up of 79 months (1-265 months), the LR rate was 8% and 2% among patients with DCIS and invasive cancer, respectively. CONCLUSION: NC-LCIS is rarely present in association with DCIS or invasive cancer, and it does not appear to impact LR outcomes following BCS.

Insights into methionine S-methylation in diverse organisms.

Dimethylsulfoniopropionate (DMSP) is an important marine anti-stress compound, with key roles in global nutrient cycling, chemotaxis and, potentially, climate regulation. Recently, diverse marine Actinobacteria, α- and γ-proteobacteria were shown to initiate DMSP synthesis via the methionine (Met) S-methyltransferase enzyme (MmtN), generating S-methyl-Met (SMM). Here we characterize a roseobacterial MmtN, providing structural and mechanistic insights into this DMSP synthesis enzyme. We propose that MmtN uses the proximity and desolvation mechanism for Met S-methylation with two adjacent MmtN monomers comprising the Met binding site. We also identify diverse functional MmtN enzymes in potentially symbiotic archaeal Candidatus Woesearchaeota and Candidate Phyla Radiation (CPR) bacteria, and the animalcule Adineta steineri, not anticipated to produce SMM and/or DMSP. These diverse MmtN enzymes, alongside the larger plant MMT enzyme with an N-terminus homologous to MmtN, likely utilize the same proximity and desolvation mechanism. This study provides important insights into the catalytic mechanism of SMM and/or DMSP production, and proposes roles for these compounds in secondary metabolite production, and SMM cycling in diverse organisms and environments.

Invasive lobular carcinoma with extracellular mucin (ILCEM): clinicopathologic and molecular characterization of a rare entity.

Invasive lobular carcinoma with extracellular mucin (ILCEM) is a rare histologic subtype of breast cancer. Little is known about the pathologic or genomic signatures that distinguish ILCEM from classic invasive lobular carcinoma (ILC) or mucinous carcinoma. We studied 17 breast cancers with lobular morphology and extracellular mucin. Thirteen tumors with sufficient tissue for DNA extraction were analyzed by a next generation sequencing (NGS) assay that interrogates 447 genes for mutations and copy number variations (CNVs). Median patient age was 66 yrs (range: 31-77 yrs). Sixteen patients presented with masses, 7 of which were >2 cm. Seven patients had lymph node metastases. The cases of ILCEM were moderately (n = 13) or poorly differentiated (n = 4), frequently exhibiting variant morphology that has not been previously described or emphasized, including grade 3 nuclei (n = 11), diffuse signet ring cells (n = 10), solid growth (n = 4), tumor necrosis (n = 3) or apocrine features (n = 2). All tumors showed absent or reduced membranous E-cadherin expression. Concurrent lobular carcinoma in situ (LCIS) was seen in 11/17 cases, 1 of which was a striking example of signet ring cell LCIS with extracellular mucin. Receptor profiles were ER+/HER2- (n = 15) and ER+/HER2+ (n = 2). With a median follow-up of 83.5 months (range: 3-171 months) in 12 patients with available information, 8 patients had recurrences resulting in 4 cancer-related deaths. The most common CNVs were 16q loss (n = 11) and 1q gain (n = 9). CDH1 gene-level alterations were detected in all but one case, including frameshift (n = 7), nonsense (n = 2), and donor splice site (n = 1) mutations and indels (n = 2). Recurrent mutations were also seen in PIK3CA (n = 3), POLQ (n = 3), TP53 (n = 3), ERBB3 (n = 3), ERBB2 (n = 2), and RUNX1 (n = 2). Genes with recurrent amplifications included GATA3 (n = 4), FOXA1 (n = 3), CCND1 (n = 2). Our data highlights ILCEM as a distinct variant of ILC that often presents with higher-grade and variant morphologic features and is associated with an aggressive clinical course. NGS data support an overall lobular-type molecular profile and reveal potentially targetable alterations in a subset of cases with recurrence.

Detecting Mental Health Behaviors Using Mobile Interactions: Exploratory Study Focusing on Binge Eating.

BACKGROUND: Binge eating is a subjective loss of control while eating, which leads to the consumption of large amounts of food. It can cause significant emotional distress and is often accompanied by purging behaviors (eg, meal skipping, overexercising, or vomiting). OBJECTIVE: The aim of this study was to explore the potential of mobile sensing to detect indicators of binge-eating episodes, with a view toward informing the design of future context-aware mobile interventions. METHODS: This study was conducted in 2 stages. The first involved the development of the DeMMI (Detecting Mental health behaviors using Mobile Interactions) app. As part of this, we conducted a consultation session to explore whether the types of sensor data we were proposing to capture were useful and appropriate, as well as to gather feedback on some specific app features relating to self-reporting. The second stage involved conducting a 6-week period of data collection with 10 participants experiencing binge eating (logging both their mood and episodes of binge eating) and 10 comparison participants (logging only mood). An optional interview was conducted after the study, which discussed their experience using the app, and 8 participants (n=3, 38% binge eating and n=5, 63% comparisons) consented. RESULTS: The findings showed unique differences in the types of sensor data that were triangulated with the individuals' episodes (with nearby Bluetooth devices, screen and app use features, mobility features, and mood scores showing relevance). Participants had a largely positive opinion about the app, its unobtrusive role, and its ease of use. Interacting with the app increased participants' awareness of and reflection on their mood and phone usage patterns. Moreover, they expressed no privacy concerns as these were alleviated by the study information sheet. CONCLUSIONS: This study contributes a series of recommendations for future studies wishing to scale our approach and for the design of bespoke mobile interventions to support this population.

Seroepidemiologic Investigation of a COVID-19 Outbreak Aboard a U.S. Navy Ship.

The crew of USS Kidd experienced a COVID-19 outbreak identified in April 2020. This is the earliest documented COVID-19 study with RT-PCR, serology, and pre-exposure test data on the entirety of the exposed population (n=333). Case definitions included 121 confirmed (36.3% of crewmembers) and 18 probable (5.4% of crewmembers) based on laboratory diagnostic test results. At the time of testing positive, 62 (44.6%) cases reported no symptoms. Hispanic ethnicity (AOR: 2.71, CI: 1.40-5.25) and non-smoker status (AOR: 2.28, CI: 1.26-4.12) were identified as statistically significant risk factors. This study highlights the value of rapid, onboard diagnostic testing to quickly identify an outbreak and enumerate cases, as well as the serological testing to flag potential cases missed with standard viral case identification methodologies.

MRI Changes in Breast Skin Following Preoperative Therapy for Patients with Inflammatory Breast Cancer.

RATIONALE AND OBJECTIVES: Preoperative systemic therapy (PST) followed by mastectomy and radiation improves survival for patients with inflammatory breast cancer (IBC). Residual disease within the skin post-PST adversely impacts surgical outcome and risk of local-regional recurrence (LRR). We aimed to assess magnetic resonance imaging (MRI) breast skin changes post-PST with pathologic response and its impact on surgical resectability. MATERIALS AND METHODS: We retrospectively reviewed 152 baseline and post-PST breast MRIs of 76 patients with IBC. Using the ACR-BIRADS MRI lexicon, we correlated skin thickness, qualitative enhancement, and kinetic analysis with pathologic response in the skin at mastectomy. RESULTS: Baseline MRI showed skin thickening in all 76 patients, 75/76 (99%) showed skin enhancement, 54/75 (72%) had medium/fast initial kinetics, usually with persistent delayed kinetics in 49/54 (91%). Following PST, 66/76 (87%) had residual skin thickening with 64/76 (84%) showing a decrease; 33/76 (43%) had persistent enhancement. The median thickness post-PST was 4.7 mm with residual tumor in the skin, and 3.0 mm without residual tumor (p = 0.008). Regardless of pathologic response, the majority of patients had persistent skin thickening on MRI following PST (100% [14/14] with residual tumor and 84% [52/62] without residual tumor). There was no association between post-PST skin thickness on breast MRI and rate of LRR. CONCLUSION: Patients with IBC have skin thickening and enhancement on baseline breast MRI, with a statistically significant reduction in skin thickness following successful PST. Despite persistent skin changes on MRI, patients achieving a partial or complete parenchymal response to PST may proceed to mastectomy with low LRR rates.

Digital Bodies: A controlled evaluation of a brief classroom-based intervention for reducing negative body image among adolescents in the digital age.

BACKGROUND: A growing body of research has linked social media use to negative body image. AIMS: The present research aimed to evaluate the efficacy of Digital Bodies, a brief classroom-based intervention that aims to improve adolescents' body image. METHODS: British adolescents (N = 290; Age M = 12.81; SD = 0.40; Range = 12-13; Female = 151) were cluster randomized to intervention or waiting list control groups. Measures of body satisfaction, appearance ideal internalization (thin and athletic ideal internalization) and self-objectification were completed at baseline (T1), 1-week post-intervention (T2) and 8-week follow-up (T3). RESULTS: Multi-level modelling showed adolescents in the intervention group reported improved body satisfaction at T2, in comparison to the control, and crucially this effect was sustained at T3. Additionally, girls reported less thin ideal internalization at T2 relative to the control, but this effect was not sustained at T3. No other intervention effects were found. CONCLUSIONS: Overall, the findings provide initial support for the efficacy of Digital Bodies as an intervention for improving adolescents' body satisfaction.

Mechanistic insights into the key marine dimethylsulfoniopropionate synthesis enzyme DsyB/DSYB.

Marine algae and bacteria produce approximately eight billion tonnes of the organosulfur molecule dimethylsulfoniopropionate (DMSP) in Earth's surface oceans annually. DMSP is an antistress compound and, once released into the environment, a major nutrient, signaling molecule, and source of climate-active gases. The methionine transamination pathway for DMSP synthesis is used by most known DMSP-producing algae and bacteria. The S-directed S-adenosylmethionine (SAM)-dependent 4-methylthio-2-hydroxybutyrate (MTHB) S-methyltransferase, encoded by the dsyB/DSYB gene, is the key enzyme of this pathway, generating S-adenosylhomocysteine (SAH) and 4-dimethylsulfonio-2-hydroxybutyrate (DMSHB). DsyB/DSYB, present in most haptophyte and dinoflagellate algae with the highest known intracellular DMSP concentrations, is shown to be far more abundant and transcribed in marine environments than any other known S-methyltransferase gene in DMSP synthesis pathways. Furthermore, we demonstrate in vitro activity of the bacterial DsyB enzyme from Nisaea denitrificans and provide its crystal structure in complex with SAM and SAH-MTHB, which together provide the first important mechanistic insights into a DMSP synthesis enzyme. Structural and mutational analyses imply that DsyB adopts a proximity and desolvation mechanism for the methyl transfer reaction. Sequence analysis suggests that this mechanism may be common to all bacterial DsyB enzymes and also, importantly, eukaryotic DSYB enzymes from e.g., algae that are the major DMSP producers in Earth's surface oceans.

Body talk in the digital age: A controlled evaluation of a classroom-based intervention to reduce appearance commentary and improve body image.

This research evaluates the efficacy of a classroom-based intervention - Body Talk in the Digital Age (BTIDA) - in reducing adolescents' appearance commentary and improving body image. British adolescents (N = 314; Age Range = 12-14) were cluster randomised to intervention or waiting-list control groups. Measures of appearance commentary, appearance ideal internalisation, self-objectification and body satisfaction were completed at baseline (T1), then one-week (T2) and eight-week (T3) post-intervention. Multi-level modelling showed girls who received BTIDA reported less appearance commentary engagement and thin ideal internalisation at T2 and T3, than the control, supporting the partial efficacy of BTIDA for girls. No intervention effects were found among boys.