Weight stigma as a stressor: A preliminary multi-wave, longitudinal study testing the biobehavioral pathways of the Cyclic Obesity/Weight-Based Stigma (COBWEBS) model.

Higher weight individuals often face significant weight stigma. According to the Cyclic Obesity/Weight-Based Stigma (COBWEBS) model, weight stigma operates as a stressor that increases the stress hormone cortisol and promotes comfort eating, thus resulting in weight gain. Such weight gain is harmful as it exposes individuals to further stigmatization. Thus far, no study has yet tested the mechanistic pathways of the COBWEBS model and prospective longitudinal studies are severely lacking. To fill this gap, the current study tested the biobehavioral pathways of the COBWEBS model using a 4-wave yearlong longitudinal study comprising 348 higher weight individuals. Using a structural equation modeling framework, we tested three cross lagged panel models for the putative mediator, comfort eating. The models examined either synchronous and/or lagged effects across weight stigma, perceived stress, comfort eating, weight, and future weight stigma. The best fitting model revealed significant associations between baseline weight stigma, perceived stress, and comfort eating within the same month. However, comfort eating did not significantly predict weight four months later. Weight status and baseline weight stigma both predicted future weight stigma as expected. Additionally, a separate path model with hair cortisol found that weight stigma predicted perceived stress four months later, but stress did not predict aggregate cortisol levels from months 10 and 11. Hair cortisol also did not predict later weight. This preliminary work lays the foundation for identifying modifiable targets of weight stigma, thereby offering potential avenues to reduce weight stigma's harm on higher weight individuals.

Perioperative Acute Kidney Injury.

Perioperative organ injury is among the leading causes of morbidity and mortality of surgical patients. Among different types of perioperative organ injury, acute kidney injury occurs particularly frequently and has an exceptionally detrimental effect on surgical outcomes. Currently, acute kidney injury is most commonly diagnosed by assessing increases in serum creatinine concentration or decreased urine output. Recently, novel biomarkers have become a focus of translational research for improving timely detection and prognosis for acute kidney injury. However, specificity and timing of biomarker release continue to present challenges to their integration into existing diagnostic regimens. Despite many clinical trials using various pharmacologic or nonpharmacologic interventions, reliable means to prevent or reverse acute kidney injury are still lacking. Nevertheless, several recent randomized multicenter trials provide new insights into renal replacement strategies, composition of intravenous fluid replacement, goal-directed fluid therapy, or remote ischemic preconditioning in their impact on perioperative acute kidney injury. This review provides an update on the latest progress toward the understanding of disease mechanism, diagnosis, and managing perioperative acute kidney injury, as well as highlights areas of ongoing research efforts for preventing and treating acute kidney injury in surgical patients.

Perioperative Telephone Encounters Should Be Included in the Relative Value Scale Update Committee Review of Time Spent on Total Hip and Knee Arthroplasty.

BACKGROUND: Providing care for patients undergoing hip and knee arthroplasty requires substantial effort beyond the actual replacement surgery to ensure a safe, clinical, and economically effective outcome. Recently, the Centers for Medicare and Medicaid Services has stated that the procedural codes for total hip (THA) and total knee arthroplasty (TKA) are potentially misvalued and has asked for a review by the Relative Value Scale Update Committee (RUC). The purpose of this study is to quantify one of the additional work efforts associated with telephone encounters during the perioperative episode of care. METHODS: We retrospectively reviewed all 47,841 telephone calls from patients to our office from 2015 to 2017 in a consecutive series of 3309 patients who underwent TKA and 3651 patients who underwent THA. We recorded reasons for communication, amount of communication, and the caller identity for both 30 days preoperatively and 90 days postoperatively. We then used the RUC Building Block Method to calculate the preservice and postservice work included in a review of the time and intensity of the codes for THA and TKA. RESULTS: The average number of preoperative patient calls per patient was 2.31 for TKA and 2.44 for THA, and the average number of postoperative calls was 5.01 for TKA and 4.00 for THA. The most common reasons for patient calls were perioperative care instructions, medications, medical clearance, paperwork/insurance, and complications. Using the RUC-approved work relative value units (wRVUs) assigned to each telephone encounter, an additional 1.83 wRVUs for perioperative telephone encounters for TKA and 1.61 for THA should be assigned. CONCLUSIONS: Providing patients with appropriate support during the arthroplasty episode of care requires substantial telephonic support, which should be acknowledged. As the RUC considers reviewing the time and intensity spent on perioperative care for patients undergoing THA and TKA, they should consider appropriately documenting the amount of work required for telephone communication.

A procedure for transforming indoles into indolequinones.

A procedure that converts a series of structurally diverse, readily available indole derivatives to their corresponding indolequinones is described. The three-step route commences with an iridium catalyzed C-H borylation to give a 7-borylindole that upon oxidation-hydrolysis affords the 7-hydroxyindole. Subsequent oxidation provides the indolequinone.

Reliability assessment and validation of the postacne hyperpigmentation index (PAHPI), a new instrument to measure postinflammatory hyperpigmentation from acne vulgaris.

BACKGROUND: There are no validated outcome measures for postinflammatory hyperpigmentation (PIH). OBJECTIVE: We sought to determine the reliability and validity of an outcome measure for PIH after acne in patients with skin of color. METHODS: A postacne hyperpigmentation index (PAHPI) was developed. Six raters scored 21 patients with PIH twice. Reliability was determined within and between raters, whereas validity was evaluated by comparing scores with severity ranking by an independent dermatologist. The pigment intensity scores were compared with the melanin index of each patient using a narrowband reflectance spectrophotometer. A quality-of-life score (Skindex-29) was also compared with PAHPI scores. RESULTS: Total PAHPI scores showed good reliability within and between raters and were valid when compared with clinical severity and melanin indices. Good correlation was achieved between the total PAHPI score and the emotion subscale of the Skindex-29. LIMITATIONS: Generalizability of results is limited to African American females. CONCLUSION: The PAHPI shows good reliability and validity when scored on patients with PIH from acne vulgaris. The PAHPI also correlates well with the emotional impact of PIH as measured by the Skindex-29. Future studies should assess the ability of the PAHPI to change with improvement of PIH from acne after treatment.

Examining the effect of weight-related recruitment information on participant characteristics: A randomized field experiment.

Objective: Although 82% of American adults have a body mass index (BMI) of over 25, individuals with elevated BMI are considered difficult to recruit for studies. Effective participant identification and recruitment are crucial to minimize the likelihood of sampling bias. One understudied factor that could lead to sampling bias is the study information presented in recruitment materials. In the context of weight research, potential participants with higher weight may avoid studies that advertise weight-related procedures. Thus, this study experimentally manipulated the phrasing of weight-related information included in recruitment materials and examined its impact on participants' characteristics. Methods: Two visually similar flyers, either weight-salient or neutral, were randomly posted throughout a university campus to recruit participants (N = 300) for a short survey, assessing their internalized weight bias, anticipated and experienced stigmatizing experiences, eating habits, and general demographic characteristics. Results: Although the weight-salient (vs. neutral) flyer took 18.5 days longer to recruit the target sample size, there were no between flyer differences in respondents' internalized weight bias, anticipated/experienced weight stigma, disordered eating behaviors, BMI, or perceived weight. Absolute levels of these variables, however, were low overall. Conclusion: Providing detailed information about study procedures allows participants to have more autonomy over their participation without differentially affecting participant characteristics.

Dietary Approaches to Stop Hypertension (DASH) diet and mental well-being: a systematic review.

CONTEXT: The Dietary Approaches to Stop Hypertension (DASH) diet is one of the most commonly prescribed diets for preventing and controlling hypertension. However, the relationship between the DASH diet and mental health and well-being has yet to be systematically understood. OBJECTIVE: To fill this gap, the present review systematically examined the current literature on the association between the DASH diet and mental health. DATA SOURCES: The Web of Science, PsycINFO, and PubMed databases were systematically searched to identify eligible publications up to May 2021. Interventional and observational studies published in English allowing for inferences about mental well-being were included. DATA EXTRACTION: Two authors independently assessed the quality of reviewed studies using the NIH quality assessment tool and extracted qualitative data. Conflicts were adjudicated by the senior author. DATA ANALYSIS: A total of 16 studies involving 48 824 participants were included in the final review: Ten were observational studies and 6 were randomized controlled trials. On average, the methodological quality of the studies was medium strength. Mixed results on psychological measures were reported, but in general, the DASH diet was associated with better mental well-being. Five observational studies supported a negative association between adherence to the DASH diet and depressive symptoms/depression. Four randomized controlled trials provided evidence of the beneficial effects of the DASH diet on mental health, including quality of life and emotional symptoms. CONCLUSION: The DASH diet likely has positive effects on mental well-being, but the results were inconsistent across different studies, which might be likely due to differences in methods of assessments of the DASH diet and mental health outcomes. Well-powered randomized controlled trials with mental well-being as the primary outcome are needed in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021267667.

A Novel Class of Ribosome Modulating Agents Exploits Cancer Ribosome Heterogeneity to Selectively Target the CMS2 Subtype of Colorectal Cancer.

Ribosomes in cancer cells accumulate numerous patient-specific structural and functional modifications that facilitate tumor progression by modifying protein translation. We have taken a unique synthetic chemistry approach to generate novel macrolides, Ribosome modulating agents (RMA), that are proposed to act distal to catalytic sites and exploit cancer ribosome heterogeneity. The RMA ZKN-157 shows two levels of selectivity: (i) selective translation inhibition of a subset of proteins enriched for components of the ribosome and protein translation machinery that are upregulated by MYC; and (ii) selective inhibition of proliferation of a subset of colorectal cancer cell lines. Mechanistically, the selective ribosome targeting in sensitive cells triggered cell-cycle arrest and apoptosis. Consequently, in colorectal cancer, sensitivity to ZKN-157 in cell lines and patient-derived organoids was restricted to the consensus molecular subtype 2 (CMS2) subtype that is distinguished by high MYC and WNT pathway activity. ZKN-157 showed efficacy as single agent and, the potency and efficacy of ZKN-157 synergized with clinically approved DNA-intercalating agents which have previously been shown to inhibit ribogenesis as well. ZKN-157 thus represents a new class of ribosome modulators that display cancer selectivity through specific ribosome inhibition in the CMS2 subtype of colorectal cancer potentially targeting MYC-driven addiction to high protein translation. Significance: This study demonstrates that ribosome heterogeneity in cancer can be exploited to develop selective ribogenesis inhibitors. The colorectal cancer CMS2 subtype, with a high unmet need for therapeutics, shows vulnerability to our novel selective ribosome modulator. The mechanism suggests that other cancer subtypes with high MYC activation could also be targeted.

Iridium-catalyzed C-H borylation-based synthesis of natural indolequinones.

An iridium-catalyzed C-H borylation provides the key step in a short synthesis of two indolequinone natural products. This regioselective C-H functionalization strategy delivers 7-borylindoles that undergo facile oxidation-hydrolysis to 7-hydroxyindoles and subsequent oxidation to the desired indolequinones, thereby demonstrating a powerful application of the iridium-catalyzed C-H borylation reaction. A significant result has arisen from the iridium-catalyzed borylation of N-diethylhydrosilyl-6-methoxyindole; even in the presence of a substituent at C6, the N-hydrosilyl group still directs borylation exclusively into the more sterically hindered C7 position in preference to C2.

Higher albumin levels on admission predict better prognosis in patients with confirmed COVID-19.

BACKGROUND: Research surrounding COVID-19 (coronavirus disease 2019) is rapidly increasing, including the study of biomarkers for predicting outcomes. There is little data examining the correlation between serum albumin levels and COVID-19 disease severity. The purpose of this study is to evaluate whether admission albumin levels reliably predict outcomes in COVID-19 patients. METHODS: We retrospectively reviewed 181 patients from two hospitals who had COVID-19 pneumonia confirmed by polymerase chain reaction (PCR) testing and radiologic imaging, who were hospitalized between March and July 2020. We recorded demographics, COVID-19 testing techniques, and day of admission labs. The outcomes recorded included the following: venous thromboembolism (VTE), acute respiratory distress syndrome (ARDS), intensive care unit (ICU) admission, discharge with new or higher home oxygen supplementation, readmission within 90 days, in-hospital mortality, and total adverse events. A multivariate modified Poisson regression analysis was then performed to determine significant predictors for increased adverse events in patients with COVID-19 pneumonia. RESULTS: A total of 109 patients (60.2%) had hypoalbuminemia (albumin level < 3.3 g/dL). Patients with higher albumin levels on admission had a 72% decreased risk of developing venous thromboembolism (adjusted relative risk [RR]:0.28, 95% confidence interval [CI]:0.14-0.53, p<0.001) for every 1 g/dL increase of albumin. Moreover, higher albumin levels on admission were associated with a lower risk of developing ARDS (adjusted RR:0.73, 95% CI:0.55-0.98, p = 0.033), admission to the ICU (adjusted RR:0.64, 95% CI:0.45-0.93, p = 0.019), and were less likely to be readmitted within 90 days (adjusted RR:0.37, 95% CI:0.17-0.81, p = 0.012). Furthermore, higher albumin levels were associated with fewer total adverse events (adjusted RR:0.65, 95% CI:0.52-0.80, p<0.001). CONCLUSIONS: Admission serum albumin levels appear to be a predictive biomarker for outcomes in COVID-19 patients. We found that higher albumin levels on admission were associated with significantly fewer adverse outcomes, including less VTE events, ARDS development, ICU admissions, and readmissions within 90 days. Screening patients may lead to early identification of patients at risk for developing in-hospital complications and improve optimization and preventative efforts in this cohort.

Schischkiniin support studies: synthetic access to 1,1'-bisindoles.

The first general synthetic approach to 1,1'-bisindoles is described. Two simultaneous, ambient temperature Mori-Ban reactions were used to effect bisindolization of several diallylated hydrazobenzenes with minimal cleavage of the N-N bond.

Total synthesis of the photoprotecting dipyrrolobenzoquinone (+)-terreusinone.

The first synthesis of (+)-terreusinone 1, a dipyrrolobenzoquinone with a potent UV-A protecting capability, is described. Key transformations include a one-pot Larock indolization-Sonogashira coupling reaction and the hydroamination of an unsubstituted ortho-alkynylaniline catalyzed by a cationic gold(I) complex. The synthesis proceeds in eight steps from commercially available starting materials, confirming the structure and absolute configuration of the natural product.