Validation of Long-term Recall of Pregnancy-related Weight in the Life-course Experiences And Pregnancy Study.

BACKGROUND: Prepregnancy body mass index (BMI) and gestational weight gain (GWG) are determinants of maternal and child health. However, many studies of these factors rely on error-prone self-reported measures. METHODS: Using data from Life-course Experiences And Pregnancy (LEAP), a US-based cohort, we assessed the validity of prepregnancy BMI and GWG recalled on average 8 years postpartum against medical record data treated as alloyed gold standard ("true") values. We calculated probabilities of being classified into a self-reported prepregnancy BMI or GWG category conditional on one's true category (analogous to sensitivities and specificities) and probabilities of truly being in each prepregnancy BMI or GWG category conditional on one's self-reported category (analogous to positive and negative predictive values). RESULTS: There was a tendency toward under-reporting prepregnancy BMI. Self-report misclassified 32% (95% confidence interval [CI] = 19%, 48%) of those in LEAP with truly overweight and 13% (5%, 27%) with obesity into a lower BMI category. Self-report correctly predicted the truth for 72% (55%, 84%) with self-reported overweight to 100% (90%, 100%) with self-reported obesity. For GWG, both under- and over-reporting were common; self-report misclassified 32% (15%, 55%) with truly low GWG as having moderate GWG and 50% (28%, 72%) with truly high GWG as moderate or low GWG. Self-report correctly predicted the truth for 45% (25%, 67%) with self-reported high GWG to 85% (76%, 91%) with self-reported moderate GWG. Misclassification of BMI and GWG varied across maternal characteristics. CONCLUSION: Findings can be used in quantitative bias analyses to estimate bias-adjusted associations with prepregnancy BMI and GWG.

Associations of abuse and neglect with young adult health in a population-based longitudinal cohort: Findings from Project EAT.

Childhood maltreatment (abuse and neglect) is associated with a range of negative outcomes, but a gap remains in understanding of how specific maltreatment types, particularly neglect and non-familial sexual abuse, relate to health and behavior. This study examined the association of neglect and sexual abuse (both familial and non-familial), as well as familial physical and emotional abuse, with: depressive mood and eating disorders; tobacco and marijuana use; and BMI ≥ 25 kg/m2 and BMI ≥ 30 kg/m2 in young adults. Data came from Project EAT (Eating and Activity in Teens and Young Adults), a population-based longitudinal study of weight-related health from adolescence into young adulthood. Maltreatment before age 18 was retrospectively reported at ages 26-33. Risk differences (RDs) and 95% confidence intervals (CIs) were estimated for those with a given maltreatment type to those without, and also for the cumulative number of maltreatment types experienced. One in 3 participants reported abuse or neglect. All maltreatment types were associated with at least one adverse health outcome, with physical abuse being least consistently related to the outcomes. Emotional abuse showed the strongest association with depressive mood. All maltreatment types were associated with eating disorder diagnosis, tobacco use, and marijuana use (except physical abuse for eating disorder). There was little evidence of a maltreatment association with BMI ≥ 25 kg/m2; emotional abuse and neglect were associated with BMI ≥ 30 kg/m2. Prevention of maltreatment needs to be a top public health priority.

The Association of Payer Status and Injury Patterns in Pediatric Bicycle Injuries.

BACKGROUND: Bicycle injuries continue to cause significant morbidity in the United States. How insurance status affects outcomes in children with bicycle injuries has not been defined. We hypothesized that payer status would not impact injury patterns or outcomes in pediatric bicycle-related accidents. METHODS: The National Trauma Data Bank was used to identify pediatric (≤18 y) patients involved in bicycle-related crashes admitted in year 2016. Patients with private insurance were compared with all others (uninsured, Medicaid, and Medicare). RESULTS: There were 5619 patients that met study criteria. Of these, 2500 (44%) had private insurance. Privately insured were older (12 y versus 11, P < 0.001), more likely to be white (77% versus 56%, P < 0.001), and more likely to wear a helmet (26% versus 9%, P < 0.001). On multivariate analysis, factors associated with traumatic brain injury included age (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.06-1.08; P < 0.001) and helmet use (OR, 0.64; 95% CI, 0.55-0.74; P < 0.001). Patients without private insurance were significantly less likely to wear a helmet (OR, 0.52; 95% CI, 0.44-0.63; P < 0.001). Uninsured patients had significantly higher odds of a fatal injury (OR, 4.43; 95% CI, 1.52-12.92; P = 0.006). CONCLUSIONS: Uninsured children that present to a trauma center after a bicycle accident are more likely to die. Although helmet use reduced the odds of traumatic brain injury, minorities and children without private insurance were less likely to be helmeted. Public health interventions should increase helmet access to children without private insurance, especially uninsured children.

A call to action: Feasible strategies to reduce the discard of transplantable kidneys in the United States.

Changes to the United States kidney allocation system targeted at reducing organ discard have failed to improve organ utilization. High Kidney Donor Profile Index kidneys continue to be discarded at high rates as a result of the regulatory and financial barriers to widespread utilization of these organs. However, there are potential changes to clinical practice that could improve organ utilization. Expediting the time from initial offer to final organ acceptance would reduce cold ischemic time and should improve utilization. Implementation of procurement biopsy standards to avoid biopsy of low risk organs may prevent organ discards due to inaccurate data or excessive cold ischemia time. Further, standardization of procurement biopsy pathological interpretation coupled with electronic accessibility would enable early acceptance of difficult to transplant organs. These changes to allocation practice patterns are vital given proposals to expand the geographic sharing of deceased donor kidneys. Implementation of new allocation policies must be evaluated to ensure they result in higher transplant rates and acceptable post-transplant outcomes.

MEF2B is a member of the BCL6 gene transcriptional complex and induces its expression in diffuse large B-cell lymphoma of the germinal center B-cell-like type.

Myocyte enhancer-binding factor 2B (MEF2B) has been implicated as a transcriptional regulator for BCL6. However, details about the interaction between MEF2B and BCL6 during expression, as well as the relationship of MEF2B to the expression of other germinal center (GC) markers, have not yet been fully explained. Using germinal center B-cell-like diffuse large B-cell lymphoma (GC-DLBCL) and activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) cell lines, we analyzed the expression of MEF2B and its associations with BCL6, CD10, and ERK. Furthermore, small interfering RNA (siRNA) was used to study the possible effects of MEF2B knockdown on these proteins and cell growth. Analysis of the BCL6 transcriptional complex was performed using electrophoretic mobility shift assay. The correlation between MEF2B expression and the genetic type of DLBCL was assessed using immunohistochemistry on 111 patient samples, and via in silico analysis of publicly available microarray (Gene Expression Omnibus (GEO)) datasets. Our results indicate that the expression of MEF2B protein is important for the growth of GC-DLBCL cells, as evidenced by MEF2B knockdown inhibition of cell growth and the subsequent suppression of BCL6, CD10, and ERK phosphorylation. Analysis of BCL6 transcription factors in nuclear extracts of MEF2-expressing DLBCL cells showed involvement of MEF2B with AP-2α and BCL6 proteins in the formation of the BCL6 gene transcriptional complex. Indeed, differential expression of MEF2B in the GC-DLBCL is statistically significant compared to the ABC-DLBCL in the GEO datasets, as well as in tissue microarray, as indicated via immunohistochemistry (Visco-Young algorithm). Our findings indicate that MEF2B is an essential component of the BCL6 gene transcriptional complex for the regulation of DLBCL growth via the promotion of BCL6 expression. Beyond its regulatory role in DLBCL growth, MEF2B expression correlated positively with BCL6 and CD10 expression, and was preferentially expressed in the GBC-DLBCL group.

"It Feels Like Health Care With the Patient in Mind": VA Patient and Staff Perspectives on Self-Collected HPV Testing.

PURPOSE: Self-collected testing for human papillomavirus (HPV) is poised to transform cervical cancer screening. Self-tests demonstrate similar accuracy to clinician-collected tests, but for the half a million women served by the Veterans Health Administration (VA) and their clinicians, self-collected cervical cancer screening would be a new practice. We examined VA patient and staff perspectives to inform future implementation. METHODS: Semi-structured telephone interviews were conducted between 2021 and 2022 with female veterans receiving VA care (n = 22) and VA women's health nurses, clinicians, and administrators (n = 27). Interviews were audio-recorded and transcribed. Interview questions addressed knowledge and interest, potential advantages or disadvantages, and any questions participants had about self-collected screening. Responses were analyzed using rapid qualitative methods. MAIN FINDINGS: Five overarching themes were identified. Both patients and staff indicated high interest and enthusiasm for self-collected HPV testing, tempered by questions about test accuracy and logistical considerations. Familiarity with self-testing for other conditions such as colon-cancer screening or COVID made self-collection seem like a simple, convenient option. However, self-testing was not viewed as a good fit for all patients, and concerns about lost opportunities or missed incidental lesions were raised. Patients and staff described challenges with pelvic examinations for patients with past sexual trauma, particularly in the male-dominated VA environment. Pelvic exams can leave patients feeling vulnerable and exposed; self-collected testing was seen as a mechanism for patient empowerment. PRINCIPAL CONCLUSIONS: Veteran patients and VA staff shared common perspectives about potential advantages and disadvantages of self-collected HPV testing. Self-collected HPV testing has the potential to improve trauma-informed preventive health care for veterans.

Cohort profile: Life-course experiences and pregnancy (LEAP)-A retrospective pregnancy cohort for life-course reproductive health research.

BACKGROUND: Life course factors may be associated with pre-pregnancy body mass index and gestational weight gain; however, collecting information on pre-pregnancy exposures and pregnancy health in the same cohort is challenging. OBJECTIVES: The Life-course Experiences And Pregnancy (LEAP) study aims to identify adolescent and young adult risk factors for pre-pregnancy weight and gestational weight gain (GWG). We built upon an existing cohort study to overcome challenges inherent to studying life course determinants of pregnancy health. POPULATION: Participants in an ongoing prospective cohort study of weight-related health who identified as women. DESIGN: Retrospective cohort study. METHODS: In 2019-2020, 1,252 women participating since adolescence in a cohort study of weight-related health were invited to complete an online reproductive history survey. Participants who reported a live birth were invited to release their prenatal, delivery, and postpartum medical records for validation of survey reports. Descriptive analyses were conducted to assess the characteristics of the overall cohort and the medical record validation subsample, and to describe adolescent and young adult characteristics of those with high (>80th percentile), moderate (20th-80th percentile), and low (<20th percentile) GWG z-score for gestational age and pre-pregnancy weight status. PRELIMINARY RESULTS: Nine hundred seventy-seven women (78%) completed the LEAP survey and 656 reported a live birth. Of these, 379 (58%) agreed to release medical records, and 250 records were abstracted (66% of the 379). Of the 977 survey respondents 769 (79%) reported attempting a pregnancy, and 656 (67%) reported at least one live birth. The validation subsample was similar to the overall cohort. Women with a high GWG had a higher adolescent BMI percentile and prevalence of unhealthy weight control behaviors than those with moderate or low GWG. CONCLUSIONS: LEAP offers a valuable resource for identifying life course factors that may influence the health of pregnant people and their offspring.

Email recruitment for chronic pain clinical trials: results from the LAMP trial.

BACKGROUND: Recruitment for clinical trials and large-scale studies is challenging, especially for patients with complex conditions like chronic pain. Email recruitment has the potential to increase efficiency, to reduce costs, and to improve access for underrepresented patient populations. The objective of this study was to examine the effectiveness, efficiency, and equitability of email versus postal mail recruitment for the Learning to Apply Mindfulness to Pain (LAMP) study, a three-site clinical trial of mindfulness-based interventions for chronic pain. METHODS: Patients with chronic pain diagnoses were recruited from three United States Department of Veterans Affairs (VA) facilities using the VA electronic health record (EHR). Recruitment materials were sent using either postal mail (n = 7986) or email (n = 19,333). Patients in the email recruitment group were also mailed introductory postcards before any emails. Mailing addresses and email addresses were obtained from the EHR. Effectiveness was measured by the response rate of patients who logged into the secure LAMP study website. Efficiency was measured by the number of days from when the recruitment materials were sent to when patients logged into the LAMP portal as well as the estimated costs of each recruitment approach. To assess equitability, we examined whether email recruitment was less effective for underrepresented populations, based on demographic information from the EHR. RESULTS: Effectiveness-unadjusted response rates were greater for email versus postal-mail recruitment (18.9% versus 6.3%), and adjusted response rates were over three times greater for email recruitment (RR = 3.5, 95% CI 3.1-3.8) based on a multivariable analysis controlling for age, gender, race, ethnicity, rurality, and site. Efficiency-email recruitment had a significantly lower mean response time (1 day versus 8 days) and a lower cost. Equity-email recruitment led to higher response rates for all subpopulations, including older, non-White, Hispanic, rural, and female Veterans. CONCLUSIONS: Email recruitment is an effective, efficient, and equitable way to recruit VA patients to large-scale, chronic pain clinical trials. TRIAL REGISTRATION: Clinical Trial Registration Number: NCT04526158. Patient enrollment began on December 4, 2020.

Relationships between Applied Mindfulness Practice, Chronic Pain, and Pain-Related Functioning in Veterans.

Mindfulness-based interventions (MBIs) have been shown to improve chronic pain and associated conditions like depression, anxiety, and sleep disorders. However, there is limited research on how Veterans with chronic pain apply mindfulness skills to manage pain in daily life. This cross-sectional study examined the association between applied mindfulness practice, pain, and several pain-related conditions among 1,737 Veterans with chronic pain prior to enrollment in a trial of two MBIs. Applied mindfulness practice was assessed using the Applied Mindfulness Process Scale (AMPS). Outcomes included pain interference, pain intensity, pain catastrophizing, fatigue, sleep disturbance, anxiety, depression, PTSD, physical function, and social participation. Higher overall AMPS scores, as well as the positive and negative emotional regulation subscales of the AMPS, were associated with less pain interference and catastrophizing, as well as better outcomes for all pain-related conditions. The positive emotional regulation subscale had the strongest associations with outcomes. There was no significant association between the AMPS and pain intensity. Results suggest applied mindfulness practice, especially positive emotional regulation, may improve pain and functioning. In addition, the AMPS shows promise as a process measure of mindfulness skills applied in daily life. Additional research is needed to examine different aspects of mindfulness in the context of MBIs. PERSPECTIVE: This article describes the relationship between applied mindfulness practice and pain-related outcomes, prior to a mindfulness-based intervention, using a novel measure of mindfulness practice. These findings underscore the importance of measuring applied mindfulness practice prior to and during clinical interventions to treat chronic pain.

Gender differences in PTSD severity and pain outcomes: Baseline results from the LAMP trial.

BACKGROUND: Post-traumatic stress disorder (PTSD) and chronic pain are highly prevalent comorbid conditions. Veterans dually burdened by PTSD and chronic pain experience more severe outcomes compared to either disorder alone. Few studies have enrolled enough women Veterans to test gender differences in pain outcomes [catastrophizing, intensity, interference] by the severity of PTSD symptoms. AIM: Examine gender differences in the association between PTSD symptoms and pain outcomes among Veterans enrolled in a chronic pain clinical trial. METHODS: Participants were 421 men and 386 women Veterans with chronic pain who provided complete data on PTSD symptoms and pain outcomes. We used hierarchical linear regression models to examine gender differences in pain outcomes by PTSD symptoms. RESULTS: Adjusted multivariable models indicated that PTSD symptoms were associated with higher levels of pain catastrophizing (0.57, 95% CI [0.51, 0.63]), pain intensity (0.30, 95% CI [0.24, 0.37]), and pain interference (0.46, 95% CI [0.39, 0.52]). No evidence suggesting gender differences in this association were found in either the crude or adjusted models (all interaction p-values<0.05). CONCLUSION: These findings may reflect the underlying mutual maintenance of these conditions whereby the sensation of pain could trigger PTSD symptoms, particularly if the trauma and pain are associated with the same event. Clinical implications and opportunities testing relevant treatments that may benefit both chronic pain and PTSD are discussed.

Exploring Gender Differences in Veterans in a Secondary Analysis of a Randomized Controlled Trial of Mindfulness for Chronic Pain.

Background: Although studies have documented higher rates of chronic pain among women Veterans compared to men Veterans, there remains a lack of comprehensive information about potential contributors to these disparities. Materials and Methods: This study examined gender differences in chronic pain and its contributors among 419 men and 392 women Veterans, enrolled in a mindfulness trial for chronic pain. We conducted descriptive analyses summarizing distributions of baseline measures, obtained by survey and through the electronic health record. Comparisons between genders were conducted using chi-square tests for categorical variables and t-tests for continuous measures. Results: Compared to men, women Veterans were more likely to have chronic overlapping pain conditions and had higher levels of pain interference and intensity. Women had higher prevalence of psychiatric and sleep disorder diagnoses, greater levels of depression, anxiety, post-traumatic stress disorder, fatigue, sleep disturbance, stress and pain catastrophizing, and lower levels of pain self-efficacy and participation in social roles and activities. However, women were less likely to smoke or have a substance abuse disorder and used more nonpharmacological pain treatment modalities. Conclusion: Among Veterans seeking treatment for chronic pain, women differed from men in their type of pain, had greater pain intensity and interference, and had greater prevalence and higher levels of many known biopsychosocial contributors to pain. Results point to the need for pain treatment that addresses the comprehensive needs of women Veterans.Clinical Trial Registration Number: NCT04526158. Patient enrollment began on December 4, 2020.

The receptor for advanced glycation end products mediates lung endothelial activation by RBCs.

The receptor for advanced glycation end products (RAGE) is a multiligand pattern recognition receptor implicated in multiple disease states. Although RAGE is expressed on systemic vascular endothelium, the expression and function of RAGE on lung endothelium has not been studied. Utilizing in vitro (human) and in vivo (mouse) models, we established the presence of RAGE on lung endothelium. Because RAGE ligands can induce the expression of RAGE and stored red blood cells express the RAGE ligand N(ε)-carboxymethyl lysine, we investigated whether red blood cell (RBC) transfusion would augment RAGE expression on endothelium utilizing a syngeneic model of RBC transfusion. RBC transfusion not only increased lung endothelial RAGE expression but enhanced lung inflammation and endothelial activation, since lung high mobility group box 1 and vascular cell adhesion molecule 1 expression was elevated following transfusion. These effects were mediated by RAGE, since endothelial activation was absent in RBC-transfused RAGE knockout mice. Thus, RAGE is inducibly expressed on lung endothelium, and one functional consequence of RBC transfusion is increased RAGE expression and endothelial activation.

The role of prior trauma exposure and subsequent posttraumatic stress disorder in reactions to the COVID-19 pandemic: A qualitative study.

OBJECTIVE: A growing body of literature suggests that the COVID-19 pandemic is a traumatic stressor capable of causing posttraumatic stress symptoms. People with a history of trauma, particularly those with posttraumatic stress disorder (PTSD), may be particularly vulnerable to the negative mental health impacts of the pandemic. However, qualitative research exploring potential differences in the lived experiences of and reactions to COVID-19 between people with and without PTSD is lacking. METHOD: Semistructured interviews were conducted with 31 women (n = 15 women with probable PTSD, n = 16 women without probable PTSD) recruited from an ongoing U.S.-based cohort study. Themes were identified using inductive thematic analysis. RESULTS: The majority of women with PTSD described their level of fear or perceived safety related to COVID-19 as a major factor influencing their mental health during the pandemic. In contrast, women without PTSD indicated that their level of distress was largely driven by pandemic-related restrictions on normal activities and family events. Many women with PTSD also described feeling anger or frustration toward people they perceived as not taking the COVID-19 pandemic seriously. Only one participant without PTSD expressed similar feelings. CONCLUSIONS: This study found notable differences in reactions to the COVID-19 pandemic between people with and without PTSD, with findings that are likely relevant to future disasters. These findings can inform the development of preparedness policies for future disasters, pandemics, or other collective traumas to prevent distress and improve mental health, particularly for vulnerable populations such as individuals with preexisting PTSD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Succinate metabolism and membrane reorganization drives the endotheliopathy and coagulopathy of traumatic hemorrhage.

Acute hemorrhage commonly leads to coagulopathy and organ dysfunction or failure. Recent evidence suggests that damage to the endothelial glycocalyx contributes to these adverse outcomes. The physiological events mediating acute glycocalyx shedding are undefined, however. Here, we show that succinate accumulation within endothelial cells drives glycocalyx degradation through a membrane reorganization-mediated mechanism. We investigated this mechanism in a cultured endothelial cell hypoxia-reoxygenation model, in a rat model of hemorrhage, and in trauma patient plasma samples. We found that succinate metabolism by succinate dehydrogenase mediates glycocalyx damage through lipid oxidation and phospholipase A2-mediated membrane reorganization, promoting the interaction of matrix metalloproteinase 24 (MMP24) and MMP25 with glycocalyx constituents. In a rat hemorrhage model, inhibiting succinate metabolism or membrane reorganization prevented glycocalyx damage and coagulopathy. In patients with trauma, succinate levels were associated with glycocalyx damage and the development of coagulopathy, and the interaction of MMP24 and syndecan-1 was elevated compared to healthy controls.

Alcohol-related Opioid Overdose Deaths in Minnesota Between 2011 and 2020: Trends by Sex.

OBJECTIVES: To characterize the overall trend and differences by sex in opioid overdose death (OOD) and alcohol-related opioid overdose deaths (AOOD) in Minnesota between 2011 and 2020 in relation to drug overdose deaths. METHODS: Using Minnesota death certificate data from 2011 to 2020, we identified OOD and AOOD among Minnesota residents aged 15 and older who died of a drug overdose death. We calculated significant differences in the annual proportion of OOD and AOOD and sex differences using Pearson x2 tests. RESULTS: Approximately 59% of all drug overdose deaths are attributed to opioids, and 18% of those deaths are alcohol-related. Significant increases in the proportion of OOD were found between 2019 and 2020 and a significant decrease between 2017 and 2018 for women only. No significant changes were found in the overall proportion of AOOD. Men had higher on average proportions of OOD and alcohol-related OOD. CONCLUSIONS: Proportions of OOD in relation to overdose deaths increased between 2011 and 2020, with a precipitous increase between 2019 and 2020 while the proportion of AOOD remained relatively stable over the period. Alcohol remains a contributing factor in approximately 1 in 5 OODs in Minnesota. These results support the need for accessible, evidence-based prevention and treatment programs to prevent drug overdose.

Alterations to cavefish red blood cells provide evidence of adaptation to reduced subterranean oxygen.

Animals inhabiting extreme environments allow the powerful opportunity to examine adaptive evolution in response to diverse pressures. One such pressure is reduced oxygen, commonly present at high-altitude and subterranean environments. Cave-dwelling animals must also deal with darkness and starvation, both of which have been rigorously studied as key forces driving the evolution of cave-associated traits. Interestingly, hypoxia as an environmental pressure has received less attention. Here we examined putatively adaptive phenotypes evolving in a freshwater teleost fish, Astyanax mexicanus, which includes both surface- and cave-dwelling forms. This model system also provides the opportunity to identify convergent responses to hypoxia, owing to the presence of numerous natural and independently-colonised cave populations, alongside closely-related surface conspecifics. The focus of this study is hemoglobin, an essential molecule for oxygen transport and delivery. We found that multiple cave populations harbor a higher concentration of hemoglobin in their blood, which is coincident with an increase in cave morph erythrocyte size compared to surface fish. Interestingly, both cave and surface morphs have comparable numbers of erythrocytes per unit of blood, suggesting elevated hemoglobin is not due to overproduction of red blood cells. Alternatively, owing to an increased cell area of erythrocytes in cavefish, we reason that they contain more hemoglobin per erythrocyte. These findings support the notion that cavefish have adapted to hypoxia in caves through modulation of both hemoglobin production and erythrocyte size. This work reveals an additional adaptive feature of Astyanax cavefish, and demonstrates that coordinated changes between cellular architecture and molecular changes are necessary for organisms evolving under intense environmental pressure.

The influence of childhood and early adult adversities on substance use behaviours in racial/ethnically diverse young adult women: a latent class analysis.

Childhood and adult adversities occur more frequently among women and persons of colour, possibly influencing racial/ethnic disparities in substance use behaviours. This study investigates how childhood and adult adversities cluster together by race/ethnicity and how these clusters predict binge drinking, tobacco, e-cigarette, and marijuana use. Latent class analysis (LCA) was used in a combined sample from the 2015 to 2018 Minnesota College Student Health Survey to identify clusters of childhood and adult adversities among Asian, Black, Latina, and White women aged 18-25. Each substance use outcome was regressed on each adversity cluster across each race/ethnicity group. Across all racial/ethnic groups and substance use outcomes, the high adversity cluster exhibited the greatest risk. Significant racial/ethnic disparities were observed across several substance use behaviours; these were attenuated among women with fewer adversities. The reduced substance use disparities found among those with lower adversities suggest that prevention of adversities may advance health equity.

Resolution of Disseminated Angiosarcoma in a Kidney Transplant Recipient After Treatment With Sirolimus: A Case Report.

Angiosarcoma is a rare, almost universally fatal malignant neoplasm in kidney transplant recipients. No evidence-based guidelines are available for disseminated disease. Here, we report a case of a 66-year-old woman who developed disseminated angiosarcoma 4 months after living nonrelated kidney transplant. She underwent only 2 rounds of chemotherapy because of intolerable adverse effects. Her mycophenolic acid and tacrolimus were withdrawn and sirolimus use was started. In addition to its immunosuppressant effects, sirolimus has been shown to have antineoplastic properties. Remarkably, at almost 2 years post-transplant, the patient has had complete resolution of all gross metastatic disease with only immunosuppressant medication changes. This case highlights the interesting possibility that sirolimus is an effective adjunct treatment for disseminated angiosarcoma in kidney transplant recipients.

Ancillary treatment of patients with lung disease due to non-tuberculous mycobacteria: a narrative review.

Background and Objective: Non-tuberculous mycobacterial lung disease (NTM-LD) manifests with bronchiectasis, inflammatory bronchiolitis, nodules, and/or cavitation. Bronchiectasis is characterized by permanently dilated airways wherein mucus accumulates, creating a vicious cycle of chronic injurious inflammation and recurrent infections. While antibiotics are an important part of the treatment of NTM-LD, airway clearance techniques to mitigate this pathogenic mechanism of bronchiectasis as well as other ancillary measures are also important components of NTM-LD treatment. The objective of this contemporaneous Narrative Review is to emphasize the importance of such ancillary measures. Methods: We searched PubMed for the key words of "airway clearance", "pulmonary rehabilitation", "nutrition", "swallowing dysfunction", "gastroesophageal reflux", "vestibular dysfunction", or "cochlear dysfunction" with that of "non-tuberculous mycobacterial lung disease", "bronchiectasis", or "respiratory disease". The bibliographies of identified articles were further searched for relevant articles not previously identified. Each relevant article was reviewed by one or more of the authors and a narrative review was composed. Key Content and Findings: Herein, we discuss five ancillary treatment measures that are pertinent to patients with bronchiectasis and NTM-LD: (I) airway clearance; (II) physical and pulmonary rehabilitation; (III) nutrition; (IV) diagnosis and mitigation of swallowing dysfunction and of gastroesophageal reflux disease (GERD); and (V) minimization of vestibular and cochlear dysfunction associated with some anti-NTM drugs. Conclusions: While antibiotics is often the central focus of treatment of NTM-LD, given its propensity for recurrent and recalcitrant infection, other ancillary measures to break the vicious cycle of injurious inflammation and infection should also be emphasized to optimize treatment success.

Discovery of a potent and highly selective PDK1 inhibitor via fragment-based drug discovery.

We report the use of a fragment-based lead discovery method, Tethering with extenders, to discover a pyridinone fragment that binds in an adaptive site of the protein PDK1. With subsequent medicinal chemistry, this led to the discovery of a potent and highly selective inhibitor of PDK1, which binds in the 'DFG-out' conformation.