Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 78
Filter
Add more filters

Country/Region as subject
Publication year range
1.
Ann Plast Surg ; 90(6): 547-550, 2023 06 01.
Article in English | MEDLINE | ID: mdl-37311310

ABSTRACT

BACKGROUND: Foley catheter placement is often advised in surgeries anticipated to exceed 3 hours; however, this time cutoff does not take into account the type of surgery. Complications from Foley catheter placement include urinary tract infections and genitourinary trauma that may be costly to healthcare systems. Our objective was to determine whether mastectomy with or without reconstruction can be done without Foley use, without an increase in urinary retention risk. METHODS: One hundred eighty-seven patients who underwent unilateral or bilateral mastectomies with or without reconstruction in 2020 and 2021 were reviewed. Chart review included intraoperative fluids given, estimated blood loss, lymph node dissection, and duration of procedure. RESULTS: After excluding patients with case duration under 180 minutes, 145 remained. Ninety-four patients did not have a Foley and 51 patients had an intraoperative Foley. None of the patients without a Foley experienced postoperative urinary retention, including 3 patients who also underwent lymphatic microsurgical preventive healing approach. Eighty-six percent of patients were discharged on the day of surgery. Patients with or without a Foley did not differ significantly in terms of race, rate of axillary lymph node dissection, body mass index, rate of same-day discharge, presence of hypertension or diabetes, estimated blood loss, or age. CONCLUSIONS: Patients undergoing unilateral and bilateral mastectomies with or without reconstruction or lymphatic microsurgical preventive healing approach may avoid Foley catheter placement without increased risk of urinary retention, even if the case is anticipated to exceed 3 hours. Advantages include elimination of catheter-associated urinary tract infections and their associated hospital costs, as well as avoiding genitourinary trauma.


Subject(s)
Body Fluids , Breast Neoplasms , Urinary Retention , Humans , Female , Urinary Retention/etiology , Urinary Retention/therapy , Breast Neoplasms/surgery , Mastectomy , Catheters
2.
BMC Med Educ ; 23(1): 457, 2023 Jun 20.
Article in English | MEDLINE | ID: mdl-37340427

ABSTRACT

OBJECTIVES: A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. METHODS: This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students' data. RESULTS: We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest-posttest differences in students' readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students' social interaction anxiety after the IPE simulation. CONCLUSIONS: The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education.


Subject(s)
Interprofessional Education , Students, Health Occupations , Humans , Learning , Problem Solving , Universities , Interprofessional Relations , Attitude of Health Personnel
3.
Langmuir ; 38(33): 10075-10080, 2022 Aug 23.
Article in English | MEDLINE | ID: mdl-35914231

ABSTRACT

The molecular architecture of sugar-based surfactants strongly affects their self-assembled structure, i.e., the type of micelles they form, which in turn controls both the dynamics and rheological properties of the system. Here, we report the segmental and mesoscopic structure and dynamics of a series of C16 maltosides with differences in the anomeric configuration and degree of tail unsaturation. Neutron spin-echo measurements showed that the segmental dynamics can be modeled as a one-dimensional array of segments where the dynamics increase with inefficient monomer packing. The network dynamics as characterized by dynamic light scattering show different relaxation modes that can be associated with the micelle structure. Hindered dynamics are observed for arrested networks of worm-like micelles, connected to their shear-thinning rheology, while nonentangled diffusing rods relate to Newtonian rheological behavior. While the design of novel surfactants with controlled properties poses a challenge for synthetic chemistry, we demonstrate how simple variations in the monomer structure can significantly influence the behavior of surfactants.

4.
Int J Mol Sci ; 23(5)2022 Feb 23.
Article in English | MEDLINE | ID: mdl-35269583

ABSTRACT

The fourth enzymatic reaction in the de novo pyrimidine biosynthesis, the oxidation of dihydroorotate to orotate, is catalyzed by dihydroorotate dehydrogenase (DHODH). Enzymes belonging to the DHODH Class II are membrane-bound proteins that use ubiquinones as their electron acceptors. We have designed this study to understand the interaction of an N-terminally truncated human DHODH (HsΔ29DHODH) and the DHODH from Escherichia coli (EcDHODH) with ubiquinone (Q10) in supported lipid membranes using neutron reflectometry (NR). NR has allowed us to determine in situ, under solution conditions, how the enzymes bind to lipid membranes and to unambiguously resolve the location of Q10. Q10 is exclusively located at the center of all of the lipid bilayers investigated, and upon binding, both of the DHODHs penetrate into the hydrophobic region of the outer lipid leaflet towards the Q10. We therefore show that the interaction between the soluble enzymes and the membrane-embedded Q10 is mediated by enzyme penetration. We can also show that EcDHODH binds more efficiently to the surface of simple bilayers consisting of 1-palmitoyl, 2-oleoyl phosphatidylcholine, and tetraoleoyl cardiolipin than HsΔ29DHODH, but does not penetrate into the lipids to the same degree. Our results also highlight the importance of Q10, as well as lipid composition, on enzyme binding.


Subject(s)
Dihydroorotate Dehydrogenase/chemistry , Dihydroorotate Dehydrogenase/metabolism , Escherichia coli/enzymology , Lipid Bilayers/metabolism , Ubiquinone/metabolism , Cardiolipins/metabolism , Escherichia coli Proteins/chemistry , Escherichia coli Proteins/metabolism , Humans , Hydrophobic and Hydrophilic Interactions , Models, Molecular , Phosphatidylcholines/metabolism , Protein Conformation , Protein Domains
5.
Int J Mol Sci ; 22(18)2021 Sep 07.
Article in English | MEDLINE | ID: mdl-34575837

ABSTRACT

Labeling of proteins with deuterium (2H) is often necessary for structural biology techniques, such as neutron crystallography, NMR spectroscopy, and small-angle neutron scattering. Perdeuteration in which all protium (1H) atoms are replaced by deuterium is a costly process. Typically, expression hosts are grown in a defined medium with heavy water as the solvent, which is supplemented with a deuterated carbon source. Escherichia coli, which is the most widely used host for recombinant protein production, can utilize several compounds as a carbon source. Glycerol-d8 is often used as a carbon source for deuterium labelling due to its lower cost compered to glucose-d7. In order to expand available options for recombinant protein deuteration, we investigated the possibility of producing a deuterated carbon source in-house. E. coli can utilize pyruvate as a carbon source and pyruvate-d3 can be made by a relatively simple procedure. To circumvent the very poor growth of E. coli in minimal media with pyruvate as sole carbon source, adaptive laboratory evolution for strain improvement was applied. E. coli strains with enhanced growth in minimal pyruvate medium was subjected to whole genome sequencing and the genetic changes were revealed. One of the evolved strains was adapted for the widely used T7 RNA polymerase overexpression systems. Using the improved strain E. coli DAP1(DE3) and in-house produced deuterated carbon source (pyruvic acid-d4 and sodium pyruvate-d3), we produce deuterated (>90%) triose-phosphate isomerase, at quantities sufficient enough for large volume crystal production and subsequent analysis by neutron crystallography.


Subject(s)
Deuterium/metabolism , Escherichia coli/metabolism , Pyruvic Acid/metabolism , Recombinant Proteins/metabolism , Sodium/metabolism , Adaptation, Physiological , Culture Media , Escherichia coli/genetics , Escherichia coli/growth & development , Gene Expression Regulation, Bacterial , Isotope Labeling , Magnetic Resonance Spectroscopy , Mutation , Recombinant Proteins/genetics
6.
J Surg Oncol ; 122(6): 1173-1178, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32638405

ABSTRACT

BACKGROUND AND OBJECTIVES: Due to the rarity of appendiceal mucinous neoplasms (AMNs), there are few established treatment guidelines. The clinical course varies from incidental detection to progressive spread with pseudomyxoma peritonei (PMP). This study investigated the extent of resection on the prognosis and outcomes of AMNs. METHODS: This multicenter retrospective study evaluated patients with AMN who underwent surgery between 4/2006 to 9/2017. Primary endpoints included overall survival (OS) and disease-specific survival (DSS). Secondary endpoints included PMP incidence and treatment with cytoreductive surgery (CRS). RESULTS: Of the 138 patients with AMN, 70 patients (54%) underwent appendectomy, 26 (19%) cecectomy, and 37 (27%) right hemicolectomy. The median age was 59.7 years and 57 patients (41%) were male. Males were less likely to undergo cecectomy (P = .03). Rupture rates, tumor characteristics, and incidence of PMP were similar across surgery groups. Median follow-up was 61.3 months. Five-year OS and DSS for the total cohort were 94.9% and 98.6%, respectively, and remained similar across all surgery groups. CRS patients were more likely to undergo right hemicolectomy with no difference in survival by surgery type (P = .03). CONCLUSIONS: Patients with AMN have a good overall prognosis and there may be minimal benefit to performing extended surgical resection in these patients.


Subject(s)
Adenocarcinoma, Mucinous/surgery , Appendectomy/mortality , Appendiceal Neoplasms/surgery , Cytoreduction Surgical Procedures/mortality , Peritoneal Neoplasms/surgery , Adenocarcinoma, Mucinous/pathology , Aged , Appendiceal Neoplasms/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Peritoneal Neoplasms/pathology , Prognosis , Retrospective Studies , Survival Rate
7.
Environ Monit Assess ; 192(7): 466, 2020 Jun 29.
Article in English | MEDLINE | ID: mdl-32602080

ABSTRACT

The concentrations of six heavy metal/metalloids (HMs) cadmium (Cd), copper (Cu), mercury (Hg), lead (Pb), zinc (Zn), and arsenic (As) were determined in the influent, effluent, and dewatered sludge of two sewage treatment works (Yuen Long Sewage Treatment Work (YLSTW) and Shek Wu Hui Sewage Treatment Work (SWHSTW)) and river waters and sediment (Shan Pui River and Ng Tung River) within the Mai Po Ramsar site in Hong Kong SAR, China. In both STWs, Pb had the highest removal efficiencies (YLSTW 86.5 ± 19.0% to 97.3 ± 3.04%; SWHSTW 87.4 ± 12.8% to 100 ± 0.0800%). In the whole effluent toxicity test, both STWs were effective in lowering the toxicity of the effluent to zebrafish and cherry shrimp. The environmental risk assessments of these HMs on three local aquatic organisms, three species of fish, two species of crustaceans, and three species of algae, were calculated based on measured HMs concentrations in river water and sewage samples, and the predicted no-effect concentrations. Results showed that Zn concentrations in all collected samples posed potential risks to all studied aquatic organisms (average risk quotient = 445). The concentrations of Cu in the rivers posed potential risks (average risk quotient = 5.42) to all fish species. It was concluded that Zn and Hg derived from the STWs might pose potential risks to the living organisms inhabiting the Ramsar site, and Cu, Cd, Pb, and As in the rivers were originated from the two rivers and possibly other tributaries.


Subject(s)
Metalloids/analysis , Metals, Heavy/analysis , Water Pollutants, Chemical/analysis , Animals , China , Environmental Monitoring , Geologic Sediments , Hong Kong , Risk Assessment , Rivers , Sewage
8.
Angew Chem Int Ed Engl ; 59(24): 9388-9392, 2020 Jun 08.
Article in English | MEDLINE | ID: mdl-32167645

ABSTRACT

The formation of excitons in OLEDs is spin dependent and can be controlled by electron-paramagnetic resonance, affecting device resistance and electroluminescence yield. We explore electrically detected magnetic resonance in the regime of very low magnetic fields (<1 mT). A pronounced feature emerges at zero field in addition to the conventional spin- 1 / 2 Zeeman resonance for which the Larmor frequency matches that of the incident radiation. By comparing a conventional π-conjugated polymer as the active material to a perdeuterated analogue, we demonstrate the interplay between the zero-field feature and local hyperfine fields. The zero-field peak results from a quasistatic magnetic-field effect of the RF radiation for periods comparable to the carrier-pair lifetime. Zeeman resonances are resolved down to 3.2 MHz, approximately twice the Larmor frequency of an electron in Earth's field. However, since reducing hyperfine fields sharpens the Zeeman peak at the cost of an increased zero-field peak, we suggest that this result may constitute a fundamental low-field limit of magnetic resonance in carrier-pair-based systems. OLEDs offer an alternative solid-state platform to investigate the radical-pair mechanism of magnetic-field effects in photochemical reactions, allowing models of biological magnetoreception to be tested by measuring spin decoherence directly in the time domain by pulsed experiments.

9.
Langmuir ; 35(25): 8344-8356, 2019 06 25.
Article in English | MEDLINE | ID: mdl-31122018

ABSTRACT

For evolving biological and biomedical applications of hybrid protein?lipid materials, understanding the behavior of the protein within the lipid mesophase is crucial. After more than two decades since the invention of the in meso crystallization method, a protein-eye view of its mechanism is still lacking. Numerous structural studies have suggested that integral membrane proteins preferentially partition at localized flat points on the bilayer surface of the cubic phase with crystal growth occurring from a local fluid lamellar L? phase conduit. However, studies to date have, by necessity, focused on structural transitions occurring in the lipid mesophase. Here, we demonstrate using small-angle neutron scattering that the lipid bilayer of monoolein (the most commonly used lipid for in meso crystallization) can be contrast-matched using deuteration, allowing us to isolate scattering from encapsulated peptides during the crystal growth process for the first time. During in meso crystallization, a clear decrease in form factor scattering intensity of the peptides was observed and directly correlated with crystal growth. A transient fluid lamellar L? phase was observed, providing direct evidence for the proposed mechanism for this technique. This suggests that the peptide passes through a transition from the cubic QII phase, via an L? phase to the lamellar crystalline Lc phase with similar layered spacing. When high protein loading was possible, the lamellar crystalline Lc phase of the peptide in the single crystals was observed. These findings show the mechanism of in meso crystallization for the first time from the perspective of integral membrane proteins.


Subject(s)
Crystallization/methods , Lipid Bilayers/chemistry , Glycerides/chemistry , X-Ray Diffraction
10.
J Environ Manage ; 225: 17-24, 2018 Nov 01.
Article in English | MEDLINE | ID: mdl-30071363

ABSTRACT

Restoration of disturbed habitats (e.g., landfills and mine tailings) is important to recover ecosystem services. Arbuscular mycorrhizal (AM) fungal community is an important indicator of ecological performance of ecosystems. Rhizospheric soils were collected in two sites (A1 and A2) within the restored area of a landfill (18 yrs after restoration), and two sites (B and C, serving as control) in the adjacent natural area. Soil properties were analysed. AM fungal communities in soils were analysed by sequencing 18S small subunit rRNA gene. Results showed that genera Glomus (the most abundant, relative abundance: 10-24%), Paraglomus and Rhizophagus were commonly found at all sites. Acaulospora and Redeckera were found exclusively at natural sites, while Scutellospora only at the restored site. On average, AM fungal species richness was lower (87 operational taxonomy units, OTUs), while diversity was higher (Shannon index 3.2) in restored site, compared with control (107 OTUs, Shannon index 2.8). The structure of the AM fungal communities was influenced by soil nitrogen and cation exchange capacity. The restored sites possessed a more phylogenetically heterogeneous fungal community than that in natural sites. AM fungal community at restored sites clearly deviated from that at natural sites, indicating that current restoration practice is certainly inadequate. The trend of ecological succession could be significantly influenced by rehabilitation methods, such as adjustment of initial soil properties and selection of plant species. This study highlights the necessity of assessing AM fungal community during ecological restoration for sustainable ecosystem, in addition to plant and bacteria.


Subject(s)
Mycorrhizae , Soil Microbiology , Waste Disposal Facilities , Biodiversity , Ecosystem , Soil
11.
Ann Surg Oncol ; 22(8): 2492-9, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25515198

ABSTRACT

BACKGROUND: For elderly patients with early-stage breast cancer, the standards of care often are not strictly followed due to either clinician biases or patient preferences. The authors hypothesized that forgoing radiation and lymph node (LN) staging for elderly patients with early-stage breast cancer would have a negative impact on survival. METHODS: From the Surveillance, Epidemiology, and End Results Program database, 53,619 women older than 55 years with stage 1 breast cancer who underwent breast conservation surgery were identified. Analyses were performed to compare the characteristics and outcomes of patients who received the standards of care with LN sampling and radiation and those of patients who did not, with control used for confounders. To account for selection bias from covariate imbalance, propensity score matching was performed. Survival was analyzed using the Kaplan-Meier method. RESULTS: Older patients were less likely to receive radiation and LN sampling. These standards of care were associated with improved overall survival rates of 15.8 and 27.1 % after 10 years, respectively (p ≤ 0.0001). This survival advantage persisted after propensity score matching, with a 7.4 % higher survival rate for patients who received radiation and a 16.8 % higher survival rate for those who underwent LN staging (p < 0.0001). Lymph node sampling and radiation therapy also conferred a statistically significant improvement in breast cancer-specific survival, with 1.3 and 2.6 % lower mortality rates respectively in the radiated and LN biopsy groups (p < 0.0001). CONCLUSIONS: As patients age, they are less likely to receive the standard of care for stage 1 breast cancer. Even after controlling for other factors, the study showed that failure to adhere to the standards of LN sampling and radiation therapy may have a negative impact in survival.


Subject(s)
Breast Neoplasms/pathology , Breast Neoplasms/radiotherapy , Lymph Nodes/pathology , Sentinel Lymph Node Biopsy , Standard of Care , Aged , Aged, 80 and over , Breast Neoplasms/surgery , Female , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Mastectomy, Segmental , Middle Aged , Neoplasm Staging , Patient Preference , Practice Patterns, Physicians' , Propensity Score , SEER Program , Survival Rate
12.
J Surg Res ; 193(1): 135-44, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25145901

ABSTRACT

BACKGROUND: The generation of reactive oxygen species (ROS) and their resultant oxidative damage is a common pathway for gastric mucosal injury. Developing strategies to protect the gastric epithelium against oxygen free radical damage is of profound pathophysiological interest. We have previously shown caspase-mediated apoptosis as a major cause of ROS-induced cell death in gastric mucosa. Because heat shock proteins (Hsps) confer protection against many cytotoxic agents, this study was undertaken to determine whether modulation of Hsps was protective against oxidative damage. MATERIALS AND METHODS: AGS cells (human gastric mucosal cell line) received either no pretreatment, heat shock pretreatment (1 h at 42 ± 1°C), or pretreatment with an Hsp modulating drug (geldanamycin or quercetin). Cells were then exposed to hydrogen peroxide (H2O2), a representative ROS (1 mM, a physiologically relevant concentration), for 24 h. Caspase-3 activation and Poly ADP Ribose Polymerase (PARP) inactivation, as well as DNA-histone complex formation were used as measures of apoptosis. Inducible Hsps (Hsp70 and Hsp90) were detected using Western blot analysis. RESULTS: Results showed heat shock pretreatment induced increased expression of Hsp70 without change in Hsp90. In response to H2O2 exposure alone, there was significant increase in DNA-histone complex formation as well as caspase-3 activation and PARP cleavage in gastric epithelium. Heat shock pretreatment resulted in statistically significant prevention in these measures of apoptosis. Geldanamycin increased Hsp70, but elicited cleavage of Hsp90 and subsequently resulted in an increase in H2O2-induced apoptosis. Quercetin decreased Hsp70 and resulted again in increased H2O2-induced apoptosis. CONCLUSIONS: These findings indicate that heat shock pretreatment protects gastric mucosal cells against H2O2-induced apoptosis and that Hsp70 and Hsp90 may play key roles in this process. These results further suggest that perturbations in Hsp metabolism may induce mucosal injury in response to oxygen free radicals.


Subject(s)
Adenocarcinoma/metabolism , Apoptosis/physiology , HSP70 Heat-Shock Proteins/metabolism , HSP90 Heat-Shock Proteins/metabolism , Reactive Oxygen Species/metabolism , Stomach Neoplasms/metabolism , Adenocarcinoma/pathology , Apoptosis/drug effects , Benzoquinones/pharmacology , Caspase 3/metabolism , Cell Line, Tumor , Enzyme Inhibitors/pharmacology , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Hot Temperature , Humans , Hydrogen Peroxide/pharmacology , Lactams, Macrocyclic/pharmacology , Oxidants/pharmacology , Poly(ADP-ribose) Polymerases/metabolism , Stomach Neoplasms/pathology
13.
Breast J ; 21(5): 526-32, 2015.
Article in English | MEDLINE | ID: mdl-26104795

ABSTRACT

Interest is growing in preventing readmissions as payers start to link reimbursement to readmission rates. The purpose of this study was to assess factors that contribute to 30-day readmission rates for women undergoing mastectomy for breast cancer. Data from the Pennsylvania Health Care Cost Containment Council were queried for women undergoing mastectomy for breast cancer during 2011 (n = 2,919). The outcomes measured were length of stay (LOS) and 30-day readmission. Univariate comparisons between characteristics of readmitted (n = 172) and nonreadmitted patients were performed using t-tests and chi-square tests. Readmission was modeled using logistic regression; LOS was modeled using linear regression and controlled for potential confounders. In multivariate analyses, patients with peripheral vascular disease were more likely to be readmitted (OR 4.36, p = 0.002). Increased LOS was also associated with increased odds of readmission (OR 1.26, p = <0.0001). Since LOS was an important predictor of readmission we also estimated determinants of LOS using linear regression. The occurrence of reconstructive surgery (p = <0.0001) and renal disease (p < 0.0001) were highly predictive of longer LOS. This study showed peripheral vascular disease and longer lengths of stay were associated with higher odds of readmission in women undergoing mastectomy. Clinicians should be cognizant that optimizing a patient's vascular status before mastectomy may lead to lower rates of readmission. Additional research is needed to determine whether the relationship between readmissions and length of hospital stay is a causative versus associative phenomenon since LOS is a modifiable factor that may lead to lower readmissions.


Subject(s)
Breast Neoplasms/therapy , Length of Stay/statistics & numerical data , Mastectomy/statistics & numerical data , Patient Readmission/statistics & numerical data , Adult , Breast Neoplasms/epidemiology , Female , Humans , Linear Models , Middle Aged , Multivariate Analysis , Postoperative Complications/epidemiology , Reoperation , Risk Factors , Severity of Illness Index
14.
Org Biomol Chem ; 12(41): 8239-46, 2014 Nov 07.
Article in English | MEDLINE | ID: mdl-25199510

ABSTRACT

The first enantioselective total syntheses of the proposed structures of the natural product prevezol B are reported. The reported syntheses complement the previously-reported syntheses of the proposed structures of prevezol C, a stereoisomer of prevezol B. It was previously shown that the structure of the naturally occurring prevezol C had been incorrectly assigned. This work has led us to conclude that the proposed structures of prevezol B are also incorrect and major revision of both of the structures of the prevezols B and C is required. Cytotoxicity studies on the human cervical cancer cell line HeLa revealed that the synthesized prevezol B and C compounds were not active even at the highest concentration used (100 µM). However, one of the synthetic precursors was shown to have modest potency against HeLa cells (IC50 = 23.5 ± 1.8 µM).


Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Diterpenes/pharmacology , Antineoplastic Agents/chemistry , Biological Products/chemical synthesis , Biological Products/chemistry , Cell Proliferation/drug effects , Diterpenes/chemical synthesis , Diterpenes/chemistry , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HeLa Cells , Humans , Molecular Conformation , Molecular Structure , Stereoisomerism , Structure-Activity Relationship
15.
ACS Nano ; 18(28): 18314-18326, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38949563

ABSTRACT

Proteins are adjustable units from which biomaterials with designed properties can be developed. However, non-native folded states with controlled topologies are hardly accessible in aqueous environments, limiting their prospects as building blocks. Here, we demonstrate the ability of a series of anhydrous deep eutectic solvents (DESs) to precisely control the conformational landscape of proteins. We reveal that systematic variations in the chemical composition of binary and ternary DESs dictate the stabilization of a wide range of conformations, that is, compact globular folds, intermediate folding states, or unfolded chains, as well as controlling their collective behavior. Besides, different conformational states can be visited by simply adjusting the composition of ternary DESs, allowing for the refolding of unfolded states and vice versa. Notably, we show that these intermediates can trigger the formation of supramolecular gels, also known as eutectogels, where their mechanical properties correlate to the folding state of the protein. Given the inherent vulnerability of proteins outside the native fold in aqueous environments, our findings highlight DESs as tailorable solvents capable of stabilizing various non-native conformations on demand through solvent design.


Subject(s)
Gels , Protein Folding , Proteins , Solvents , Solvents/chemistry , Proteins/chemistry , Gels/chemistry , Protein Conformation
16.
Am Surg ; : 31348241244632, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38567700

ABSTRACT

INTRODUCTION: Management of stage IV colorectal cancer with synchronous liver metastases remains debated, as colorectal and liver resections can be performed simultaneously or staged apart. OBJECTIVE: This study aims to determine any demographic or outcome differences between simultaneous and staged resection. PARTICIPANTS: Retrospective review was performed on patients diagnosed with synchronous colorectal primary and liver metastases within Southern California Kaiser Permanente (KP) hospitals between 2010 and 2020. Patients with other metastases on diagnosis or those who did not receive both primary and liver resections were excluded. Demographic and outcome data were collected and analyzed. RESULTS: Of the 113 patients who met criteria, 72 (63.7%) received simultaneous and 41 (36.3%) received staged resection. Demographic data were comparable between simultaneous and staged resection, respectively, including median age of diagnosis, sex, and race. Both groups had similar median length of stay, percentage of major colorectal resection, and percentage of major liver resection. Both groups also had similar rates of radiation therapy, chemotherapy, and immunotherapy. There were no statistically significant difference in complications rates, median follow-up time, median overall survival, and median disease-free survival. CONCLUSIONS: Practice patterns within Southern California KP hospitals favor minor colorectal and liver resections. However, there were no significant differences in demographics, treatment rates, or outcomes between simultaneous and staged resection. While not statistically significant, our findings of a 11.9% higher major liver resection rate and 7.5-month longer median disease-free survival in the staged resection group may benefit from further study with higher power datasets.

17.
J Colloid Interface Sci ; 672: 244-255, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-38838632

ABSTRACT

HYPOTHESIS: Nonionic surfactants can counter the deleterious effect that anionic surfactants have on proteins, where the folded states are retrieved from a previously unfolded state. However, further studies are required to refine our understanding of the underlying mechanism of the refolding process. While interactions between nonionic surfactants and tightly folded proteins are not anticipated, we hypothesized that intermediate stages of surfactant-induced unfolding could define new interaction mechanisms by which nonionic surfactants can further alter protein conformation. EXPERIMENTS: In this work, the behavior of three model proteins (human growth hormone, bovine serum albumin, and ß-lactoglobulin) was investigated in the presence of the anionic surfactant sodium dodecylsulfate, the nonionic surfactant ß-dodecylmaltoside, and mixtures of both surfactants. The transitions occurring to the proteins were determined using intrinsic fluorescence spectroscopy and far-UV circular dichroism. Based on these results, we developed a detailed interaction model for human growth hormone. Using nuclear magnetic resonance and contrast-variation small-angle neutron scattering, we studied the amino acid environment and the conformational state of the protein. FINDINGS: The results demonstrate the key role of surfactant cooperation in defining the conformational state of the proteins, which can shift away or toward the folded state depending on the nonionic-to-ionic surfactant ratio. Dodecylmaltoside, initially a non-interacting surfactant, can unexpectedly associate with sodium dodecylsulfate-unfolded proteins to further impact their conformation at low nonionic-to-ionic surfactant ratio. When this ratio increases, the protein begins to retrieve the folded state. However, the native conformation cannot be fully recovered due to remnant surfactant molecules still adsorbed to the protein. This study demonstrates that the conformational landscape of the protein depends on a delicate interplay between the surfactants, ultimately controlled by the ratio between them, resulting in unpredictable changes in the protein conformation.


Subject(s)
Lactoglobulins , Protein Unfolding , Serum Albumin, Bovine , Sodium Dodecyl Sulfate , Surface-Active Agents , Surface-Active Agents/chemistry , Humans , Lactoglobulins/chemistry , Protein Unfolding/drug effects , Sodium Dodecyl Sulfate/chemistry , Cattle , Serum Albumin, Bovine/chemistry , Animals , Human Growth Hormone/chemistry , Anions/chemistry , Protein Refolding/drug effects , Protein Conformation , Glucosides
18.
HPB (Oxford) ; 15(1): 40-8, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23216778

ABSTRACT

OBJECTIVES: Gallbladder carcinoma (GBC) is a rare disease that is often diagnosed incidentally in its early stages. Simple cholecystectomy is considered the standard treatment for stage I GBC. This study was conducted in a large cohort of patients with stage I GBC to test the hypothesis that the extent of surgery affects survival. METHODS: The National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database was queried to identify patients in whom microscopically confirmed, localized (stage I) GBC was diagnosed between 1988 and 2008. Surgical treatment was categorized as cholecystectomy alone, cholecystectomy with lymph node dissection (C + LN) or radical cholecystectomy (RC). Age, gender, race, ethnicity, T1 sub-stage [T1a, T1b, T1NOS (T1 not otherwise specified)], radiation treatment, extent of surgery, cause of death and survival were assessed by log-rank and Cox's regression analyses. RESULTS: Of 2788 patients with localized GBC, 1115 (40.0%) had pathologically confirmed T1a, T1b or T1NOS cancer. At a median follow-up of 22 months, 288 (25.8%) had died of GBC. Five-year survival rates associated with cholecystectomy, C + LN and RC were 50%, 70% and 79%, respectively (P < 0.001). Multivariate analysis showed that surgical treatment and younger age were predictive of improved disease-specific survival (P < 0.001), whereas radiation therapy portended worse survival (P = 0.013). CONCLUSIONS: In the largest series of patients with stage I GBC to be reported, survival was significantly impacted by the extent of surgery (LN dissection and RC). Cholecystectomy alone is inadequate in stage I GBC and its use as standard treatment should be reconsidered.


Subject(s)
Carcinoma/surgery , Cholecystectomy , Gallbladder Neoplasms/surgery , Age Factors , Aged , Aged, 80 and over , Carcinoma/mortality , Carcinoma/secondary , Cholecystectomy/adverse effects , Cholecystectomy/mortality , Female , Gallbladder Neoplasms/mortality , Gallbladder Neoplasms/pathology , Humans , Kaplan-Meier Estimate , Lymph Node Excision , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Proportional Hazards Models , Radiotherapy, Adjuvant , Risk Factors , SEER Program , Time Factors , Treatment Outcome , United States/epidemiology
19.
Environ Geochem Health ; 34(3): 323-35, 2012 Jun.
Article in English | MEDLINE | ID: mdl-21881861

ABSTRACT

Concentrations and distributions of selected fluoroquinolones (norfloxacin, ciprofloxacin and enrofloxacin) in water, sediments and nine kinds of fish species collected from 6 sites in two marine aquaculture regions of the Pearl River Delta, China, were analyzed by using high-performance liquid chromatography with fluorescence detector (HPLC). The results showed that the concentrations of ciprofloxacin and enrofloxacin were below the limits of quantification (LOQ) in all water samples except for norfloxacin. Norfloxacin and ciprofloxacin concentrations ranged from 1.88 to 11.20 ng g(-1) dry wt, 0.76-2.42 ng g(-1) dry wt in sediments collected from the Dapeng'ao region (sites 1-3) and ranged from 2.31 to 4.75 ng g(-1) dry wt, 1.26-1.76 ng g(-1) dry wt in sediments collected from the Hailing Island region (sites 4-6), respectively. However, no enrofloxacin was found in all sediment samples. The three fluoroquinolones (FQs) were detected in all fish samples, and the concentrations were higher in liver tissues than those in muscle tissues. The levels of norfloxacin were higher than ciprofloxacin and enrofloxacin in both liver and muscle tissues. Among the nine marine fish species, Siganus fuscescens from Hailing Island had a significantly high level of norfloxacin in liver tissue (254.58 ng g(-1) wet wt), followed by Sparus macrocephalus (133.15 ng g(-1) wet wt) from Dapeng'ao, and the lowest value was Lutianus argentimaculatus (5.18 ng g(-1) wet wt) from Hailing Island. The obtained results of FQs in present study do not represent a risk to the human health in Guangdong coastal area, based on the maximum residue limits (MRLs) established by Chinese Government and the acceptable daily intake (ADI) recommended by the Food and Agriculture Organization and World Health Organization (FAO/WHO).


Subject(s)
Anti-Infective Agents/analysis , Ciprofloxacin/analysis , Norfloxacin/analysis , Perciformes/metabolism , Water Pollutants, Chemical/analysis , Animals , Anti-Infective Agents/metabolism , China , Chromatography, High Pressure Liquid , Ciprofloxacin/metabolism , Environmental Monitoring/standards , Geologic Sediments/analysis , Humans , Limit of Detection , Norfloxacin/metabolism , Risk Assessment , Seawater/analysis , Species Specificity , Water Pollutants, Chemical/metabolism
20.
J Surg Res ; 168(2): 224-30, 2011 Jun 15.
Article in English | MEDLINE | ID: mdl-20036394

ABSTRACT

BACKGROUND: Lymph node involvement is a highly important prognostic factor in colorectal cancer staging. Examination of a minimum of 12 nodes is recommended for accurate staging. The purpose of this study was to identify factors affecting the number of lymph nodes harvested in colorectal cancer specimens. MATERIALS AND METHODS: Retrospective review of all patients undergoing colectomy for colorectal cancer at our VA hospital from 2002 to 2007 was done. Statistical analysis was done using univariate as well as multivariate analysis. One hundred eighty-three patients were analyzed. RESULTS: Average number of nodes retrieved was 14.9 with 92 (51%) containing fewer than 12 lymph nodes. Median number of nodes was 11. The only two factors found to have an effect on nodes harvested were pathologist P<0.05 and surgeon experience P=0.01. Factors not found to have an impact on number of nodes harvested were age of patient, previous operation, T stage of tumor, type of colectomy, bowel prep, laparoscopic versus open technique, or BMI. Multivariate analysis confirmed pathologist and surgeon experience as independent factors associated with number of nodes retrieved P<0.05. CONCLUSIONS: Operating surgeon and examining pathologist were the only factors found to have a significant impact on number of nodes harvested. Meticulous dissection both in and outside of the operating room are indicated.


Subject(s)
Colorectal Neoplasms/surgery , Lymph Node Excision/standards , Adult , Aged , Aged, 80 and over , Body Mass Index , Colectomy , Colorectal Neoplasms/pathology , Humans , Laparoscopy , Middle Aged , Multivariate Analysis , Neoplasm Staging , Retrospective Studies
SELECTION OF CITATIONS
SEARCH DETAIL