In an effort to elucidate and engineer interactions in type II nonribosomal peptide synthetases, we analyzed biomolecular recognition between the essential peptidyl carrier proteins and adenylation domains using NMR spectroscopy, molecular dynamics, and mutational studies. Three peptidyl carrier proteins, PigG, PltL, and RedO, in addition to their cognate adenylation domains, PigI, PltF, and RedM, were investigated for their cross species activity. Of the three peptidyl carrier proteins, only PigG, showed substantial cross-pathway activity. Characterization of the novel NMR solution structure of holo-PigG and molecular dynamic simulations of holo-PltL and holo-PigG revealed differences in structures and dynamics of these carrier proteins. NMR titration experiments revealed perturbations of the chemical shifts of the loop 1 residues of these peptidyl carrier proteins upon their interaction with adenylation domain. These experiments revealed a key region for the protein-protein interaction. Mutational studies supported the role of loop 1 in molecular recognition, as mutations to this region of the PCPs significantly modulated their activities.

PurposeAvailability of comorbidity assessment at multi-disciplinary team (MDT) discussions is cornerstone in making the MDT process more robust and decisive in optimising treatment and improving quality of survivorship. Comorbidity assessments using tools, such as the ACE-27 questionnaire would aid in optimising the decision-making process at MDTs so that treatment decisions can be made without delay. This study determined the availability of comorbidity data in a CRC MDT and the feasibility of routine comorbidity data collection using the validated ACE-27 questionnaire. Secondary aims determined the optimal time and method of collecting comorbidity data.MethodsA retrospective mapping exercise (phase I; 6-months) examined the availability of comorbidity data within the MDT. Phase II prospectively collected comorbidity data using ACE-27 for a 3-month period following a short pilot.ResultsIn phase I, 73/135 (54%) patients had comorbidity data readily available informing the MDT discussion; 62 patients lacked this information. After a review of the patient records, it was clear that 41 of these 62 also had comorbidities and 21 out of the 135 had ≥ 2 major system disorders. Common referral sources to the MDT were surgical outpatient clinics (42%) and the endoscopy unit (13%). The average lead-time from referral to MDT discussion was 14 days. In phase II, an ACE-27 questionnaire was prospectively administered in 50 patients, mean age 54 years (range 20–84). Male: female ratio 26:24. Average time to administer ACE-27 was 4.8 min (range 1–15).ConclusionsThe phase I study confirmed the widely acknowledged view of poor comorbidity data availability within a CRC MDT. Phase II demonstrated the feasibility of routinely collecting comorbidity data using ACE-27.

Background: Nearly half of U.S. women experienced new or worsening health-related socioeconomic risks (HRSRs) (food, housing, utilities and transportation difficulties, and interpersonal violence) early in the COVID-19 pandemic. We sought to examine racial/ethnic disparities in pandemic-related changes in HRSRs among women. Materials and Methods: We conducted a cross-sectional survey (04/2020) of 3200 women. Pre-and early pandemic HRSRs were described by race/ethnicity. Weighted, multivariable logistic regression models generated odds of incident and worsening HRSRs by race/ethnicity. Results: The majority of Black, East or Southeast (E/SE) Asian, and Hispanic women reported ‡1 prepandemic HRSR (51%-56% vs. 38% of White women, p < 0.001). By April 2020, 68% of Black, E/SE Asian, and Hispanic women and 55% of White women had ‡1 HRSR ( p < 0.001). For most HRSRs, the odds of an incident or worsening condition were similar across racial/ethnic groups, except Black, E/SE Asian and Hispanic women had 2-3.6 times the odds of incident transportation difficulties compared with White women. E/SE Asian women also had higher odds of worsening transportation difficulties compared with White women (adjusted odds ratios = 2.5, 95% confidence interval 1.1-5.6). In the early pandemic, 1/19 Hispanic, 1/28 E/SE Asian, 1/36 Black and 1/100 White women had all 5 HRSRs (extreme health-related socioeconomic vulnerability). Conclusions: Prepandemic racial/ethnic disparities in HRSRs persisted and prevalence rates increased for all groups early in the pandemic. Disparities in transportation difficulties widened. White women were much less likely than others to experience extreme health-related socioeconomic vulnerability. An equitable COVID-19 response requires attention to persistent and widening racial/ethnic disparities in HRSRs among women.

Key Points Breath analysis is a feasible novel method to detect and potentially monitor graft-versus-host disease.

PURPOSE Family and friends who provide regular care for a sick or dependent individual ("caregivers") are at increased risk of health-related socioeconomic vulnerabilities (HRSVs). This study examined pre-pandemic prevalence of and early pandemic changes in HRSVs among women caregivers compared with non-caregivers.METHODS A cross-sectional survey was conducted in April 2020 (early pandemic) with 3,200 English-speaking US women aged 18 years or older, 30% of whom identified as caregivers. We modeled adjusted odds of self-reported HRSVs (financial strain, food/ housing insecurity, interpersonal violence, transportation/utilities difficulties) before and changes during the early pandemic by caregiving status. Models were adjusted for age, race/ethnicity, marital status, education, income, number of people in household, number of children in household, physical and mental health, and number of comorbidities. RESULTSPre-pandemic, 63% of caregivers and 47% of non-caregivers reported 1 or more vulnerability (P <.01); food insecurity was most prevalent (48% of caregivers vs 33% of non-caregivers, P <.01). In the early pandemic, caregivers had higher odds than non-caregivers of financial strain, both incident (adjusted odds ratio [AOR] = 2.1; 95% CI, 1.6-2.7) and worsening (AOR = 2.0; 95% CI, 1.4-2.8); incident interpersonal violence (AOR = 2.0; 95% CI, 1.5 -2.7); incident food insecurity (AOR = 1.6; 95% CI, 1.2-2.1); incident transportation difficulties (AOR = 1.9; 95% CI, 1.3-2.6); and incident housing insecurity (AOR = 1.6; 95% CI, 1.1-2.3). CONCLUSIONThe coronavirus disease 2019 (COVID-19) pandemic increased risk of incident and worsening HRSVs for caregivers more than for non-caregivers. COVID-19 response and recovery efforts should target caregivers to reduce modifiable HRSVs and promote the health of caregivers and those who depend on them.

Untreated pain after surgery leads to poor patient satisfaction, longer hospital length of stay, lower health-related quality of life, and non-compliance with rehabilitation regimens. The aim of this study is to characterize the structure of acute pain trajectories during the postsurgical hospitalization period and quantify their association with pain at 30-days and 1-year after surgery. This cohort study included 2106 adult (≥18 years) surgical patients who consented to participate in the SATISFY-SOS registry (February 1, 2015 to September 30, 2017). Patients were excluded if they did not undergo invasive surgeries, were classified as outpatients, failed to complete follow up assessments at 30-days and 1-year following surgery, had greater than 4-days of inpatient stay, and/or recorded fewer than four pain scores during their acute hospitalization period. The primary exposure was the acute postsurgical pain trajectories identified by a machine learning-based latent class approach using patient-reported pain scores. Clinically meaningful pain (≥3 on a 0–10 scale) at 30-days and 1-year after surgery were the primary and secondary outcomes, respectively. Of the study participants (N = 2106), 59% were female, 91% were non-Hispanic White, and the mean (SD) age was 62 (13) years; 41% of patients underwent orthopedic surgery and 88% received general anesthesia. Four acute pain trajectory clusters were identified. Pain trajectories were significantly associated with clinically meaningful pain at 30-days (p = 0.007), but not at 1-year (p = 0.79) after surgery using covariate-adjusted logistic regression models. Compared to Cluster 1, the other clusters had lower statistically significant odds of having pain at 30-days after surgery (Cluster 2: [OR = 0.67, 95%CI (0.51–0.89)]; Cluster 3:[OR = 0.74, 95%CI (0.56–0.99)]; Cluster 4:[OR = 0.46, 95%CI (0.26–0.82)], all p<0.05). Patients in Cluster 1 had the highest cumulative likelihood of pain and pain intensity during the latter half of their acute hospitalization period (48–96 hours), potentially contributing to the higher odds of pain during the 30-day postsurgical period. Early identification and management of high-risk pain trajectories can help in ascertaining appropriate pain management interventions. Such interventions can mitigate the occurrence of long-term disabilities associated with pain.

No abstract

No abstract