Differences in outcomes by race/ethnicity after thoracic surgery in a large integrated health system.

Background: Disparities exist throughout surgery. We aimed to assess for racial/ethnic disparities among outcomes in a large thoracic surgery patient population. Methods: We reviewed all thoracic surgery patients treated at our integrated health system from January 1, 2016-December 31, 2020. Post-operative outcomes including length of stay (LOS), 30-day return to the emergency department (30d-ED), 30-day readmission, 30- and 90-day outpatient appointments, and 30- and 90-day mortality were compared by race/ethnicity. Bivariate analyses and multivariable logistic regression were performed. Our multivariable models adjusted for age, sex, body mass index, Charlson Comorbidity Index, surgery type, neighborhood deprivation index, insurance, and home region. Results: Of 2730 included patients, 59.4 % were non-Hispanic White, 15.0 % were Asian, 11.9 % were Hispanic, 9.6 % were Black, and 4.1 % were Other. Median (Q1-Q3) LOS (in hours) was shortest among non-Hispanic White (37.3 (29.2-76.1)) and Other (36.5 (29.3-75.4)) patients followed by Hispanic (46.8 (29.9-78.1)) patients with Asian (51.3 (30.7-81.9)) and Black (53.7 (30.6-101.6)) patients experiencing the longest LOS (p < 0.01). 30d-ED rates were highest among Hispanic patients (21.3 %), followed by Black (19.2 %), non-Hispanic White (18.1 %), Asian (13.4 %), and Other (8.0 %) patients (p < 0.01). On multivariable analysis, Hispanic ethnicity (Odds Ratio (OR) 1.43 (95 % CI 1.03-1.97)) and Medicaid insurance (OR 2.37 (95 % CI 1.48-3.81)) were associated with higher 30d-ED rates. No racial/ethnic disparities were found among other outcomes. Conclusions: Despite parity across multiple surgical outcomes, disparities remain related to patient encounters within our system. Health systems must track such disparities in addition to standard clinical outcomes. Key message: While our large integrated health system has been able to demonstrate parity across many major surgical outcomes among our thoracic surgery patients, race/ethnicity disparities persist including in the number of post-operative return trips to the emergency department. Tracking outcome disparities to a granular level such as return visits to the emergency department and number of follow up appointments is critical as health systems strive to achieve equitable care.

Untargeted metabolomics-based identification of bioactive compounds from Mangifera indica L. seed extracts in drug discovery through molecular docking and assessment of their anticancer potential.

BACKGROUND: Mangifera indica L. (mango), a medicinal plant rich in biologically active compounds, has potential to be used in disease-preventing and health-promoting products. The present investigation reveals and uncovers bioactive metabolites with remarkable therapeutic efficiency from mango (family: Anacardiaceae) seeds. RESULTS: Biological activity was determined by antimicrobial, antioxidant and anticancer assays, and metabolite profiling was performed on gas chromatography coupled to quadrupole time-of-flight mass spectrometry (GC-QTOF-MS) and liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) platforms. Validation of active metabolites was carried out by in silico molecular docking (Molinspiration Cheminformatics Server and PASS). Extracted and identified metabolites were screened; 54 compounds associated with various groups were selected for the in silico interaction study. CONCLUSIONS: Molecular docking revealed lead molecules with a potential binding energy score, efficacy and stable modulation with a selected protein domain. Investigation, directed by in vitro and in silico analysis, confirms mango seeds as an excellent source of potential metabolites as a therapeutic agent. © 2024 Society of Chemical Industry.

Discovery of novel anticancer flavonoids as potential HDAC2 inhibitors: virtual screening approach based on molecular docking, DFT and molecular dynamics simulations studies.

Virtual screening of a library of 329 flavonoids obtained from the NPACT database was performed to find out potential novel HDAC2 inhibitors. Eleven out of 329 selected flavonoids were screened based on molecular docking studies, as they have higher binding affinities than the standard drugs vorinostat and panobinostat. All screened compounds occupying the catalytic site of HDAC2 showed important molecular interaction with Zn2+ and other important amino acids in the binding pocket. The screened compounds were validated using ADMET filtration and bioactivity prediction from which we obtained six compounds, NPACT00270, NPACT00676, NPACT00700, NPACT001008, NPACT001054, and NPACT001407, which were analyzed using DFT studies. DFT studies were performed for all six screened flavonoids. In DFT studies, three flavonoids, NPACT00700, NPACT001008, and NPACT001407, were found to be better based on HOMO-LUMO and molecular electrostatic potential (MEP) analyses. Furthermore, MD simulations were performed for 100 ns for the three compounds. In the MD analysis, NPACT001407 was found to be more stable in the active site of HDAC2 as zinc formed a coordination bond with ASP181, HIS183, ASP269, and GLY305, along with two hydroxyl groups of the ligand. Our findings reveal that these flavonoids can interact as ligands with the active site of HDAC2. Because of the absence of a hydroxamate group in flavonoids, there are no possibilities for the formation of isocyanate. This suggests that the major drawback of current HDACs inhibitors may be solved. Further experimental validation is needed to understand the selectivity of flavonoids as HDAC2 inhibitors. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03912-5.

Adjuvant Immunotherapy in Curative Intent Esophageal Cancer Resection Patients: Real-World Experience within an Integrated Health System.

BACKGROUND: Adjuvant immunotherapy has been shown in clinical trials to prolong the survival of patients with esophageal cancer. We report our initial experience with immunotherapy within an integrated health system. METHODS: A retrospective cohort study was performed reviewing patients undergoing minimally invasive esophagectomy at our institution between 2017 and 2021. The immunotherapy cohort was assessed for completion of treatment, adverse effects, and disease progression, with emphasis on patients who received surgery in 2021 and their eligibility to receive nivolumab. RESULTS: There were 39 patients who received immunotherapy and 137 patients who did not. In logistic regression, immunotherapy was not found to have a statistically significant impact on 1-year overall survival after adjusting for age and receipt of adjuvant chemoradiation. Only seven patients out of 39 who received immunotherapy successfully completed treatment (18%), with the majority failing therapy due to disease progression or side effects. Of the 17 patients eligible for nivolumab, 13 patients received it (76.4%), and three patients completed a full course of treatment. CONCLUSIONS: Despite promising findings of adjuvant immunotherapy improving the survival of patients with esophageal cancer, real-life practice varies greatly from clinical trials. We found that the majority of patients were unable to complete immunotherapy regimens with no improvement in overall 1-year survival.

Association of Surgical Timing with Outcomes in Early Stage Lung Cancer.

BACKGROUND: Optimal time to surgery for lung cancer is not well established. We aimed to assess whether time to surgery correlates with outcomes. METHODS: We assessed patients 18-84 years old who were diagnosed with stage I/II lung cancer at our integrated healthcare system from 2009 to 2019. Time to surgery was defined to start with disease confirmation (imaging or biopsy) prior to the surgery scheduling date. Outcomes of unplanned return to care within 30 days of lung cancer surgery, all-cause mortality, and disease recurrence were compared based on time to surgery before and after 2, 4, and 12 weeks. RESULTS: Of 2861 included patients, 70% were over 65 years old and 61% were female. Time to surgery occurred in 1-2 weeks for 6%, 3-4 weeks for 31%, 5-12 weeks for 58%, and 13-26 weeks for 5% of patients. Patients with time to surgery > 4 (vs. ≤ 4) weeks had greater risk of both death (hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.00-1.39) and recurrence (HR 1.33, 95% CI 1.10-1.62). Associations were not statistically significant when dichotomizing time to surgery at 2 or 12 weeks for death (2 week HR 1.23, 95% CI 0.93-1.64; 12 week HR 1.35, 95% CI 0.97-1.88) and recurrence (2 week HR 1.54, 95% CI 0.85-2.80; 12 week HR 2.28, 95% CI 0.80-6.46). CONCLUSIONS: Early stage lung cancer patients with time to surgery within 4 weeks experienced lower rates of recurrence. Optimal time to surgical resection may be shorter than previously reported.

Comparison of Survival by Multimodal Treatment Regimen Among Malignant Pleural Mesothelioma Patients in an Integrated Health System.

BACKGROUND: Optimal therapy for malignant pleural mesothelioma (MPM) remains unclear. We compared overall survival in patients with MPM after various multimodal treatment regimens including combinations of immunotherapy, chemotherapy, and surgery. PATIENTS AND METHODS: We examined MPM patients treated within our integrated health system from January 1, 2009 to December 31, 2020. Patients were grouped based on treatment regimen: chemotherapy alone (CT), immunotherapy with or without chemotherapy (iCT), surgery with chemotherapy (sCT), and surgery with immunotherapy and chemotherapy (siCT). We analyzed baseline characteristics and overall patient survival among these groups and several subgroups. RESULTS: One hundred seventy-nine patients were included. Among the study groups, there was no difference in age, sex, race/ethnicity, Charlson Comorbidity Index, or Eastern Cooperative Oncology Group performance status. Patients treated with CT (N = 109), iCT (N = 35), sCT (N = 26), and siCT (N = 9) had median (95% confidence interval) survivals of 11.7 (9.9-16.3), 18.2 (14.5-29.8), 20.7 (11.6-37.2), and 22.6 (19.7-37.8) months, respectively (P < .001). Median survival among patients with and without immunotherapy was 19.7 (17.4-29.8) and 12.3 (10.6-17.3) months, respectively (P = .023). Median survival among patients with and without surgery was 21.7 (17.6-34.8) and 13.6 (11.5-17.3) months, respectively (P = .007). Patients with biphasic/sarcomatoid subtypes who received immunotherapy experienced 76.2% (55.8%-100.0%) 12 month survival vs. 13.6% (4.8%-39.0%) among those who did not (P < .001). CONCLUSION: MPM patients receiving surgery and immunotherapy as part of multimodal treatment regimens experienced the longest survival. Surgery and immunotherapy are each associated with survival. Further investigations are warranted to assess the benefit of immunotherapy within multimodal treatment regimens for MPM.

Improving outcomes in malignant pleural mesothelioma in an integrated health care system.

Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor that should be managed by an experienced surgical and multidisciplinary group. Our objective was to determine the impact of proficient surgeons and MPM bi-disciplinary review on outcomes of patients with MPM. Methods: Through this cohort study, electronic medical records of 368 adult patients with MPM from 1/1/2009 to 12/31/2020 were reviewed and compared before and after MPM surgeries were regionalized to specialized surgeons and bi-disciplinary review of MPM patient treatment options. We used the Kaplan-Meier method and log-rank tests to compare survival rates by period, by treatment type, and by stage. Patients were followed from cancer diagnosis date until they died or end of study follow-up, whichever occurred first. We also conducted Cox proportional hazards regression model to examine the overall survival (OS) with adjustments for age, histology, stage, and Charlson comorbidity index (CCI). Results: Despite similar staging, more patients received any MPM directed treatment from 2015-2020 compared with those patients from 2009-2014. Specifically, there was an increase in patients who received pleurectomy/decortication (PD) from 2015-2020 compared to those who received PD in 2009-2014. Patients with similar age, CCI, stage, and histology had an increase in OS of 12 months with multimodality therapy (surgery, systemic therapy, +/- radiation) compared to those patients who received no treatment. Conclusions: Consolidating mesothelioma surgery to a specialized surgical team and regular bi-disciplinary review of MPM cases to determine appropriate multimodality therapy, increases the incorporation of surgical treatments in the management of patients with MPM.

Probiotic Formulations: A Patent Landscaping Using the Text Mining Approach.

The outstanding research outcomes and registrations of myriads of probiotic strains have flooded the health market with various innovative probiotic-based products and their patents. The study of patented formulations of probiotics can give an overall insight into its existing application. A landscaping review of patents for probiotic-based preparations is presented in the current work. The patent search was performed over commercially available patent databased and analysis tool-PatSeer Pro®. Search strings containing words "Formulation" and "Composition" resulted in more than 3700 patents. Landscaping review of 400 + patents from the last 20 years (2000-2020) was performed using the Text-Mining approach. Text-Mining helped to identify 19 technological clusters which represent these patents. These clusters include the patents of probiotic preparations on animal feed, human food, cosmetics, antimicrobial, antidiabetic, arthritis, etc. A review of this massive number of patents unveiled many exciting preparations. Probiotic-based innovative products for depression, diabetes, Parkinson's, tumor, acne, and animal husbandry are reviewed comprehensively. The present work also unravels a few new-flanged products like probiotic layered condoms, products for acute alcoholism, and traditional Chinese medicine with probiotics. The patent landscape of probiotic-based preparations has presented a whole scenario of probiotic-based preparations. It has also revealed many unexplored areas where innovation can be excelled.

Effect of thoracic surgery regionalization on long-term survival after lung cancer resection.

OBJECTIVE: Existing evidence demonstrates some benefit of regionalization on early postoperative outcomes following lung cancer resection, but data regarding the persistence of this effect in long-term mortality are lacking. We investigated whether previously reported improvements in short-term outcomes translated to long-term survival benefit. METHODS: We retrospectively reviewed patients undergoing major pulmonary resection (lobectomy, bilobectomy, or pneumonectomy) for cancer within our integrated health care system before (2011-2013; n = 782) and after (2015-2017; n = 845) thoracic surgery regionalization. Overall survival was compared by Kaplan-Meier analysis, and 1- and 3-year mortality was compared by the by χ2 or Fisher exact test. Multivariable Cox regression models evaluated the effect of regionalization on mortality adjusted for relevant factors. RESULTS: Kaplan-Meier curves showed that overall survival was better among patients undergoing surgery postregionalization (log-rank test, P < .0001). Both 1- and 3-year mortality were decreased after regionalization: to 5.7% from 11.1% (P < .0001) for 1 year and to 17.0% from 25.5% (P = .0002) for 3 years. The multivariable adjusted Cox regression analysis revealed that only regionalization (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.42-0.76), age (HR, 1.03; 95% CI, 1.02-1.04), cancer stage (HR, 1.72, 1.83, and 2.56 for stages II, III, and IV, respectively), and Charlson comorbidity index (HR, 1.80 for 1-2; 2.05 for ≥3) were independent predictors of mortality. CONCLUSIONS: We found that overall mortality as well as 1- and 3-year mortality for lung cancer resection were lower after thoracic surgery regionalization. The association between regionalization and reduced mortality was significant even after adjusting for other related factors in a multivariable Cox analysis. Notably, surgeon volume, facility volume, surgeon specialty, neoadjuvant treatment, and video-assisted thoracoscopic surgery approach did not significantly affect mortality in the adjusted model.

The ZEB2-dependent EMT transcriptional programme drives therapy resistance by activating nucleotide excision repair genes ERCC1 and ERCC4 in colorectal cancer.

Resistance to adjuvant chemotherapy is a major clinical problem in the treatment of colorectal cancer (CRC). The aim of this study was to elucidate the role of an epithelial to mesenchymal transition (EMT)-inducing protein, ZEB2, in chemoresistance of CRC, and to uncover the underlying mechanism. We performed IHC for ZEB2 and association analyses with clinical outcomes on primary CRC and matched CRC liver metastases in compliance with observational biomarker study guidelines. ZEB2 expression in primary tumours was an independent prognostic marker of reduced overall survival and disease-free survival in patients who received adjuvant FOLFOX chemotherapy. ZEB2 expression was retained in 96% of liver metastases. The ZEB2-dependent EMT transcriptional programme activated nucleotide excision repair (NER) pathway largely via upregulation of the ERCC1 gene and other components in NER pathway, leading to enhanced viability of CRC cells upon oxaliplatin treatment. ERCC1-overexpressing CRC cells did not respond to oxaliplatin in vivo, as assessed using a murine orthotopic model in a randomised and blinded preclinical study. Our findings show that ZEB2 is a biomarker of tumour response to chemotherapy and risk of recurrence in CRC patients. We propose that the ZEB2-ERCC1 axis is a key determinant of chemoresistance in CRC.

Regionalization of Lung Cancer Surgery Improves Outcomes in an Integrated Health Care System.

BACKGROUND: Current literature favors a volume-outcome relationship in pulmonary lobectomy that prompted centralization of these operations abroad, in national, single-payer health care settings. This study examined the impact of regionalization on outcomes after lung cancer resection within a US integrated health care system. METHODS: This study retrospectively reviewed major pulmonary resections (lobectomy, bilobectomy, pneumonectomy) for lung cancer that were performed before (2011 to 2013; n = 782) and after (2015 to 2017; n = 845) thoracic surgery regionalization during 2014. RESULTS: Case migration from 16 regionwide sites to 5 designated centers was complete by 2016. Facility volume increased from 17.4 to 48.3 cases/y (P = .002), and surgeon volume increased from 12.5 to 19.9 cases/y (P = .001). The postregionalization era was characterized by increased video-assisted thoracoscopic surgery (86% from 57%; P < .001), as well as decreased intensive care unit use (-1.0 days; P < .001) and hospital length of stay (-3.0 days; P < .001). Postregionalization patients experienced fewer total (26.2% from 38.6%; P < .001) and major (9.6% from 13.6%; P = .01) complications. The association between regionalization and decreased length of stay and morbidity was independent of surgical approach and case volume in mixed multivariate models. CONCLUSIONS: After the successful implementation of thoracic surgery regionalization in our US health care network, pulmonary resection volume increased, and practice shifted to majority video-assisted thoracoscopic surgery and minimum intensive care unit utilization. Regionalization was independently associated with significant reductions in length of stay and morbidity.

Regionalization of thoracic surgery improves short-term cancer esophagectomy outcomes.

BACKGROUND: Some studies have found that outcomes from cancer esophagectomy are better at higher-volume centers than at lower-volume centers. Reports on outcomes following systematic centralization have largely demonstrated subsequent improvements, but these originate in nationalized healthcare systems that are not very comparable to the heterogeneous private-payer systems that predominate in the United States. We examined how regionalization of thoracic surgery to Centers of Excellence (CoE) within our American integrated healthcare system changed overall care for our patients, and whether it changed outcomes. METHODS: We conducted a retrospective chart review of 461 consecutive patients undergoing cancer esophagectomy between 2009-2016, spanning the 2014 shift to regionalization. High-volume was defined as ≥5 esophagectomies per year. We compared characteristics of the surgeon, hospital, and operation pre- and post-regionalization using Chi-square or Fisher's exact test for categorical variables and Kruskal-Wallis test for age. We evaluated their associations with patient outcomes with hierarchical linear and logistic mixed models, which adjusted for clustering within surgeon and facility levels and relevant covariates. RESULTS: While there was no difference in their baseline demographics, patients undergoing esophagectomy post-regionalization were much more likely to have their surgery performed at a designated Center of Excellence (78.8% of cases versus 34.2%, P<0.001), at a high-volume hospital (92.1% from 75.7%, P<0.001), by a high-volume surgeon (78.8% from 58.8%, P<0.001), by a board-certified thoracic surgeon (82.5% from 64.0%, P<0.001), and by minimally-invasive, versus open, approach (60.8% from 22.1%, P<0.001). Post-regionalization patients were in higher American Society of Anesthesiologists classes (P=0.03) and trended toward higher-stage disease (P=0.14), indicative of the inclusion of higher-complexity patients. Despite that, regionalization was associated with improved short-term outcomes, most notably: average minimally-invasive esophagectomy (MIE) operative time decreased by 2 hours (-135.9 minutes, 95% CI: -172.2, -99.7 minutes); length of stay (LOS) decreased by 2.3 days (95% CI: -3.4, -1.2 days); and 30-day complication rate decreased significantly, from 50.7% to 30.2% (OR 0.45, 95% CI: 0.25, 0.79). Regionalization was the only variable significantly and independently associated with all three outcomes in our adjusted multivariable models. Mortality, both at 30 and 90 days, decreased modestly but was low pre-regionalization, and the difference did not reach significance. CONCLUSIONS: Regionalization of thoracic surgery in our hospital system resulted in esophagectomies being performed by more experienced surgeons at higher-volume centers, with a concomitant improvement in short-term outcomes. Patients undergoing esophagectomy, particularly MIE, post-regionalization benefited significantly from decreased LOS and perioperative complication rate. Our results suggest that, in a large integrated healthcare system, regionalization significantly improves overall outcomes for patients undergoing cancer esophagectomy.

Respiratory cancer database: An open access database of respiratory cancer gene and miRNA.

AIMS: Respiratory cancer database (RespCanDB) is a genomic and proteomic database of cancer of respiratory organ. It also includes the information of medicinal plants used for the treatment of various respiratory cancers with structure of its active constituents as well as pharmacological and chemical information of drug associated with various respiratory cancers. MATERIALS AND METHODS: Data in RespCanDB has been manually collected from published research article and from other databases. Data has been integrated using MySQL an object-relational database management system. MySQL manages all data in the back-end and provides commands to retrieve and store the data into the database. The web interface of database has been built in ASP. RESULTS AND CONCLUSIONS: RespCanDB is expected to contribute to the understanding of scientific community regarding respiratory cancer biology as well as developments of new way of diagnosing and treating respiratory cancer. Currently, the database consist the oncogenomic information of lung cancer, laryngeal cancer, and nasopharyngeal cancer. Data for other cancers, such as oral and tracheal cancers, will be added in the near future. The URL of RespCanDB is http://ridb.subdic-bioinformatics-nitrr.in/.

Risk stratification and stroke prevention therapy care gaps in Canadian atrial fibrillation patients (from the Co-ordinated National Network to Engage Physicians in the Care and Treatment of Patients With Atrial Fibrillation chart audit).

The objectives of this national chart audit (January to June 2013) of 6,346 patients with atrial fibrillation (AF; ≥18 years without a significant heart valve disorder) from 647 primary care physicians were to (1) describe the frequency of stroke and bleed risk assessments in patients with nonvalvular AF by primary care physicians, including the accuracy of these assessments relative to established predictive indexes; (2) outline contemporary methods of anticoagulation used; and (3) report the time in the therapeutic range among patients prescribed warfarin. An annual stroke risk assessment was not undertaken in 15% and estimated without a formal risk tool in 33%; agreement with CHADS2 score estimation was seen in 87% of patients. Major bleeding risk assessment was not undertaken in 25% and estimated without a formal risk tool in 47%; agreement with HAS-BLED score estimation was observed in 64% with physician overestimation in 26% of patients. Antithrombotic therapy included warfarin (58%), dabigatran (22%), rivaroxaban (14%), and apixaban (<1%). Among warfarin-treated patients, the median international normalized ratio was 2.4 and time in therapeutic range (TTR) was 73%; however, the TTR was <50% in 845 (25%), 50% to 69% in 674 (20%), and ≥70% in 1,827 (55%) patients. In conclusion, we describe a contemporary real-world elderly population with AF at important risk for stroke. There is apparent overestimation of bleeding risk in many patients. Warfarin was the dominant stroke prevention treatment; however, the suggested TTR target was achieved in only 55% of these patients.

Transfusion related iron overload in pediatric oncology patients treated at a tertiary care centre and treatment with chelation therapy.

We conducted a retrospective chart review to determine prevalence of, risk factors for, and liver toxicity associated with Transfusion Related Iron Overload (TRIO) in pediatric cancer patients, and report our experience with Iron Chelation Therapy (ICT). Total number of transfusions was identified as the major risk factor, with a prevalence of 37% in patients receiving ≥10 transfusions. Four patients with TRIO and abnormal liver function tests (LFT) received ICT. Significant decrease in serum ferritin and improvement in LFT were observed, with no serious adverse effects from ICT noted. Guidelines for screening and treatment of TRIO in pediatric oncology are needed.

Nursing home staff delivery of oral liquid nutritional supplements to residents at risk for unintentional weight loss.

OBJECTIVES: To describe nursing home (NH) staff delivery of oral liquid nutritional supplements to residents with an order to receive supplementation. DESIGN: Descriptive. SETTING: Six skilled NHs. PARTICIPANTS: One hundred thirty-two long-stay residents. MEASUREMENTS: Research staff conducted direct observations for 2 days during and between meals and documented NH staff delivery of supplements, amount consumed (fluid ounces), and amount of assistance (minutes) provided by staff to encourage consumption. RESULTS: Eighty-eight percent had an order to receive a supplement one to three times daily (mode = 3); 12% had an order to receive a supplement four to six times daily. Fewer than 10% received the supplement consistent with their orders during the 2 observation days. On average, NH staff provided a supplement less than once per participant per day during or between meals. When a supplement was provided, residents consumed an average+/-standard deviation of 4.91+/-2.19 fluid ounces during meals with 6.16+/-7.46 minutes of staff assistance and 3.98+/-2.60 fluid ounces between meals with less than 1 minute of staff assistance. Participants with orders that specified time of delivery received the supplement at a significantly higher frequency between meals. CONCLUSION: Oral liquid nutritional supplements are not provided consistent with orders in NH practice. Staff spends little time promoting supplement consumption during or between meals. The specificity of the order related to time of delivery may influence when and how often supplements are provided to residents.

Comparison of helix interactions in membrane and soluble alpha-bundle proteins.

Helix-helix interactions are important for the folding, stability, and function of membrane proteins. Here, two independent and complementary methods are used to investigate the nature and distribution of amino acids that mediate helix-helix interactions in membrane and soluble alpha-bundle proteins. The first method characterizes the packing density of individual amino acids in helical proteins based on the van der Waals surface area occluded by surrounding atoms. We have recently used this method to show that transmembrane helices pack more tightly, on average, than helices in soluble proteins. These studies are extended here to characterize the packing of interfacial and noninterfacial amino acids and the packing of amino acids in the interfaces of helices that have either right- or left-handed crossing angles, and either parallel or antiparallel orientations. We show that the most abundant tightly packed interfacial residues in membrane proteins are Gly, Ala, and Ser, and that helices with left-handed crossing angles are more tightly packed on average than helices with right-handed crossing angles. The second method used to characterize helix-helix interactions involves the use of helix contact plots. We find that helices in membrane proteins exhibit a broader distribution of interhelical contacts than helices in soluble proteins. Both helical membrane and soluble proteins make use of a general motif for helix interactions that relies mainly on four residues (Leu, Ala, Ile, Val) to mediate helix interactions in a fashion characteristic of left-handed helical coiled coils. However, a second motif for mediating helix interactions is revealed by the high occurrence and high average packing values of small and polar residues (Ala, Gly, Ser, Thr) in the helix interfaces of membrane proteins. Finally, we show that there is a strong linear correlation between the occurrence of residues in helix-helix interfaces and their packing values, and discuss these results with respect to membrane protein structure prediction and membrane protein stability.