Translational use of homing peptides: Tumor and placental targeting.

HYPOTHESIS: Tissue-specific homing peptides have been shown to improve chemotherapeutic efficacy due to their trophism for tumor cells. Other sequences that selectively home to the placenta are providing new and safer therapeutics to treat complications in pregnancy. Our hypothesis is that the placental homing peptide RSGVAKS (RSG) may have binding affinity to cancer cells, and that insight can be gained into the binding mechanisms of RSG and the tumor homing peptide CGKRK to model membranes that mimic the primary lipid compositions of the respective cells. EXPERIMENTS: Following cell culture studies on the binding efficacy of the peptides on a breast cancer cell line, a systematic translational characterization is delivered using ellipsometry, Brewster angle microscopy and neutron reflectometry of the extents, structures, and dynamics of the interactions of the peptides with the model membranes on a Langmuir trough. FINDINGS: We start by revealing that RSG does indeed have binding affinity to breast cancer cells. The peptide is then shown to exhibit stronger interactions and greater penetration than CGKRK into both model membranes, combined with greater disruption to the lipid component. RSG also forms aggregates bound to the model membranes, yet both peptides bind to a greater extent to the placental than cancer model membranes. The results demonstrate the potential for varying local reservoirs of peptide within cell membranes that may influence receptor binding. The innovative nature of our findings motivates the urgent need for more studies involving multifaceted experimental platforms to explore the use of specific peptide sequences to home to different cellular targets.

Control of the structure and morphology of polypeptide/surfactant spread films by exploiting specific interactions.

We demonstrate control of the structure and morphology of polypeptide/surfactant films at the air/water interface as a function of the maximum compression ratio of the surface area, exploiting a recently developed film formation mechanism that requires minimal quantities of materials involving the dissociation of aggregates. The systems studied are poly(L-lysine) (PLL) or poly(L-arginine) (PLA) with sodium dodecyl sulfate (SDS), chosen because the surfactant (i) interacts more strongly with the latter polypeptide due to the formation of hydrogen bonds between the guanidinium group and its oxygen atoms, and (ii) induces bulk ß-sheet and α-helix conformations of the respective polypeptides. The working hypothesis is that such different interactions may be used to tune the film properties when compressed to form extended structures (ESs). Neutron reflectometry reveals that application of a high compression ratio (4.5 : 1) results in the nanoscale self-assembly of ESs containing up to two PLL-wrapped SDS bilayers. Brewster angle microscopy provides images of the PLL/SDS ESs as discrete regions on the micrometre scale while additional linear regions of PLA/SDS ESs mark macroscopic film folding. Ellipsometry demonstrates high stability of the different ESs formed. The collapse of PLL/SDS films upon compression to a very high ratio (10 : 1) is irreversible due to the formation of solid domains that remain embedded in the film upon expansion while that of PLA/SDS films is reversible. These findings demonstrate that differences in the side group of a polypeptide can have a major influence on controlling the film properties, marking a key step in the development of this new film formation mechanism for the design of biocompatible and/or biodegradable films with tailored properties for applications in tissue engineering, biosensors and antimicrobial coatings.

A Pilot Randomized Controlled Trial Evaluating Essential Oils for Chemotherapy-Induced Peripheral Neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a painful, debilitating consequence of cancer treatment affecting up to 60% of patients. Pharmacological approaches to CIPN are often ineffective and cause adverse effects. Essential oils are an underutilized non-pharmacological approach to pain reduction. AIMS: To ascertain the efficacy of an essential oil intervention to reduce CIPN. DESIGN: A single-blind, pilot randomized controlled trial. METHODS: Participants (n = 27) were stratified by baseline pain scores and randomized to intervention (n = 13) and placebo groups (n = 14). Participants topically-applied the essential oil intervention or placebo every eight hours for six weeks. Pain was assessed using the Short-Form-McGill Pain Questionnaire-2 weekly and the Visual Analogue Scale daily. Quality-of-life was assessed using the Quality-of-Life: CIPN-20 and Quality-of-Life Adult Cancer Survivor questionnaires. Data were analyzed in SPSS using generalized estimating equations. RESULTS: No significant difference was observed between groups in pain or quality-of-life scores over seven weeks, but improvement was observed in both groups. Participants using the intervention with pain medications showed a significant reduction in pain compared to placebo (p = .001). Educational level (p = .041) and annual income (p = .005) were significant covariates mirroring these social determinates of pain. Older participants felt less negatively about their CIPN (p = .002). Positive placebo effect and spatiotemporal interactions were observed. CONCLUSIONS: This pilot study demonstrated that participants adhered to the intervention for six weeks. Essential oils have potential direct and adjuvant pain-reducing effects and should be studied further.

Longitudinal Assessment of Preterm Infants Treated with Erythropoiesis Stimulating Agents.

OBJECTIVE: We previously reported improved neurodevelopment at 2 and 4 years among preterm infants treated with erythropoietin or darbepoetin, known as erythropoiesis-stimulating agents (ESAs). We now characterize longitudinal outcomes through 6 years. METHODS: Children randomized to ESAs or placebo were evaluated at 6 years. Healthy-term children served as controls. Tests of cognition and executive function (EF) were performed. RESULTS: Cognitive/EF scores remained similar between 4 and 6 years within each group (ESA: 43 children; placebo: 17 children; term: 21 children). ESA recipients scored higher than placebo on Full-Scale IQ (94.2 ± 18.6 vs. 81.6 ± 16.7, p = 0.022), and Performance IQ (97.3 ± 16.2 vs. 81.7 ± 15.2, = 0.005). Aggregate EF trended better for the ESA group. Term controls scored better than placebo on all measures. ESA and term controls scored similarly on cognitive and EF tests. CONCLUSION: ESA recipients had better outcomes than placebo recipients, and were similar to term children. ESAs may improve long-term cognition and executive function in preterm infants.

Management of Massive Rotator Cuff Tears Without Arthropathy.

Arthroplasty is not an optimal treatment for massive rotator cuff tears in patients who are active and without glenohumeral arthritis. Several surgical techniques have been developed for these patients, including arthroscopic rotator cuff repair with single-/double-row repair (with or without interval slides, margin convergence, graft augmentation), graft bridging, superior capsular reconstruction, tuberoplasty, and tendon transfers. Complete, tension-free, anatomic repair is ideal; however, tendon atrophy and retraction associated with massive tears often complicate repairs. All surgical treatments significantly increase patient-reported functional outcomes 1 year after intervention, with many treatments demonstrating improved mid-term and long-term outcomes. [Orthopedics. 2023;46(1):e1-e12.].

Temporal association between invasive procedures and infective endocarditis.

OBJECTIVE: Antibiotic prophylaxis has been recommended for patients at increased risk of infective endocarditis (IE) undergoing specific invasive procedures (IPs) despite a lack of data supporting its use. Therefore, antibiotic prophylaxis recommendations ceased in the mid-2000s for all but those at high IE risk undergoing invasive dental procedures. We aimed to quantify any association between IPs and IE. METHODS: All 14 731 IE hospital admissions in England between April 2010 and March 2016 were identified from national admissions data, and medical records were searched for IP performed during the 15-month period before IE admission. We compared the incidence of IP during the 3 months immediately before IE admission (case period) with the incidence during the preceding 12 months (control period) to determine whether the odds of developing IE were increased in the 3 months after certain IP. RESULTS: The odds of IE were increased following permanent pacemaker and defibrillator implantation (OR 1.54, 95% CI 1.27 to 1.85, p<0.001), extractions/surgical tooth removal (OR 2.14, 95% CI 1.22 to 3.76, p=0.047), upper (OR 1.58, 95% CI 1.34 to 1.85, p<0.001) and lower gastrointestinal endoscopy (OR 1.66, 95% CI 1.35 to 2.04, p<0.001) and bone marrow biopsy (OR 1.76, 95% CI 1.16 to 2.69, p=0.039). Using an alternative analysis, bronchoscopy (OR 1.33, 95% CI 1.06 to 1.68, p=0.049) and blood transfusions/red cell/plasma exchange (OR 1.2, 95% CI 1.07 to 1.35, p=0.012) were also associated with IE. CONCLUSIONS: This study identifies a significant association between specific IPs (permanent pacemaker and defibrillator implantation, dental extraction, gastrointestinal endoscopy and bronchoscopy) and subsequent IE that warrants re-evaluation of current antibiotic prophylaxis recommendations to prevent IE in high IE risk individuals.

The shoulder function "tipping-point" for elective rotator cuff repair: demographic and longitudinal trends.

Background: A patient's decision to undergo an elective orthopedic procedure is largely based on their symptoms and functional limitations. This point where patients choose to undergo surgery is known as the "tipping point." The primary aim of this study is to determine the relationship between demographic parameters and the tipping point for elective rotator cuff repair. The secondary aim is to investigate if the tipping point is associated with mental health. The tertiary aim is to determine if the tipping point changes over time. Methods: Retrospective chart review was used to identify all patients who underwent primary arthroscopic rotator cuff repair between January 1, 2015, to January 1, 2020, with 1 of 3 board-certified orthopedic surgeons. Exclusion criteria included age <18 years, revision surgery, or incomplete datasets (American Shoulder and Elbow Surgeons [ASES], 12-item short form, demographic information, and surgical history). Preoperative ASES score was designated as the tipping point for an individual patient, with a lower score representing worse shoulder function and therefore a higher tipping point and vice versa. Demographic parameters (age, sex, body mass index [BMI], race, and insurance), hand dominance, and surgical history extracted from chart review were analyzed to determine associations with tipping point. Results: A total of 2153 patients were identified from chart review, with 1731 included in the final analysis. The patients had a mean age of 58.6 ± 9.66 years and a mean BMI of 29.2 ± 6.02 kg/m2. There was no significant difference in mean preoperative ASES score by year for the duration of this study (2015-2019, P = .27). Worker's compensation patients had a significantly lower mean preoperative ASES score than patients with commercial or government insurance (P < .01). Spearman's rank correlations showed no relationship between ASES score and patient demographics (age, sex, BMI, race, and hand dominance) or between ASES and previous orthopedic surgery. Preoperative ASES showed a weakly positive correlation (ρ = 0.26) with 12-item short form mental component score. Multivariate linear regression showed male sex is predictive of a lower tipping point (P < .01), whereas higher BMI, African American race, and history of arthroplasty are predictive of a higher tipping point (P ≤ .02). Conclusion: The tipping point was not demonstrated to change over time in our analysis. Male sex is predictive of a lower tipping point for arthroscopic rotator cuff repair, whereas elevated BMI, African American race, worker's compensation insurance, and prior arthroplasty are predictive of a higher tipping point. Also, better mental health function is associated with a lower tipping point.

Reducing Pediatric Intraoral Radiography Radiation Dose Using Reduced-Power Dental X-Ray Units: A Randomized Trial.

Purpose: To assess the diagnostic confidence of intraoral radiographic image quality while reducing the pediatric patient's radiation exposure using a longer position indicating device (PID), additional X-ray beam filtration and rectangular collimation while using modern, lower-power intraoral dental X-ray units.
Methods: A randomized prospective study scored bitewing intraoral dental images based on relevant clinical features. Observer studies with pediatric dentists and dental residents were conducted to verify whether diagnostic confidence remained unchanged after dose reduction modifications. The study involved a two-phase investigation to determine: (1) the best thickness of aluminum (Al) 2024-T3 alloy filter and (2) required increased exposure time to maintain intraoral radiographic image quality. A 30 cm PID with a rectangular collimator was used to further manage patient dose. For each phase, images from 125 patients were collected from February 2017 to September 2018 and analyzed.
Results: The results from the observer study using a 30 cm PID, 1.02 mm thick Al alloy filter, and a rectangular collimator resulted in a patient dose reduction between 64 percent (exposure time of 400 msec) to 77 percent (250 msec), without any statis- tically significant effect to the diagnostic confidence of the observers in evaluating the reduced radiation images.
Conclusion: Long recognized dose reduction methods, when implemented on a modern, low-power intraoral dental X-ray unit, do not impact confidence in bite- wing diagnostic images, but substantially reduce patient dose and should be adopted to increase patient safety, especially for children.

Insights into Extended Structures and Their Driving Force: Influence of Salt on Polyelectrolyte/Surfactant Mixtures at the Air/Water Interface.

This paper addresses the effect of polyelectrolyte stiffness on the surface structure of polyelectrolyte (P)/surfactant (S) mixtures. Therefore, two different anionic Ps with different intrinsic persistence length lP are studied while varying the salt concentration (0-10-2 M). Either monosulfonated polyphenylene sulfone (sPSO2-220, lP ∼20 nm) or sodium poly(styrenesulfonate) (PSS, lP ∼1 nm) is mixed with the cationic surfactant tetradecyltrimethylammonium bromide (C14TAB) well below its critical micelle concentration and studied with tensiometry and neutron reflectivity experiments. We kept the S concentration (10-4 M) constant, while we varied the P concentration (10-5-10-3 M of the monomer, denoted as monoM). P and S adsorb at the air/water interface for all studied mixtures. Around the bulk stoichiometric mixing point (BSMP), PSS/C14TAB mixtures lose their surface activity, whereas sPSO2-220/C14TAB mixtures form extended structures perpendicular to the surface (meaning a layer of S with attached P and additional layers of P and S underneath instead of only a monolayer of S with P). Considering the different P monomer structures as well as the impact of salt, we identified the driving force for the formation of these extended structures: compensation of all interfacial charges (P/S ratio ∼1) to maximize the gain of entropy. By increasing the flexibility of P, we can tune the interfacial structures from extended structures to monolayers. These findings may help improve applications based on the adsorption of P/S mixtures in the fields of cosmetic or oil recovery.

Lost to follow-up: does it matter after arthroscopic rotator cuff repair (a matched cohort analysis of functional outcomes).

BACKGROUND: Loss to follow-up after surgery is problematic in that it is thought to lead to poorer outcomes. There is little research on the long-term outcomes of people who have been lost to follow-up vs. patients who attended all follow-up appointments. Rotator cuff repair is unique in that the postoperative course is lengthy, and the rehabilitation program is typically tightly supervised. Therefore, the aim of this investigation is to determine whether there is any long-term difference in functional outcomes after arthroscopic rotator cuff repair between patients who are noncompliant with follow-up appointments vs. those who are compliant with all follow-up. METHODS: A database query was carried out which identified 782 patients who underwent arthroscopic rotator cuff repair at our institution during 2016. Patients were separated into 2 cohorts based on whether they were compliant with all follow-up appointments. Demographic variables such as age and sex were compiled along with objective details from surgery such as size of tear, number of anchors, and other pathologies treated. Patients who were lost to follow-up were contacted by phone to answer survey questions. A matching control group of patients who attended all follow-up appointments was identified based on demographics and surgery details using propensity score matching. The control group was then contacted by phone to answer survey questions. Statistical results were reported as P values. Minimum follow-up was set at 2 years. RESULTS: The nonsatisfactory follow-up cohort consisted of 44 people (average follow-up: 30 months), with the satisfactory follow-up cohort consisting of 57 people (average follow-up: 42 months). There was no statistical difference between groups in sex, age, American Shoulder and Elbow Surgeons scores, Single Assessment of Numeric Evaluation scores, number of anchors, number of tears, additional surgical procedures, and patient satisfaction with the surgery and the surgeon. Of the reasons patients gave for why they did not attend follow-up appointments, 25.0% felt fine or returned to work, 22.7% did not know why, 15.9% reported travel distance, 13.6% of patients gave other explanations, 11.4% reported unrelated medical issues, and 11.4% were unaware they missed any appointments. CONCLUSION: This study demonstrated that there is no difference in the outcomes of patients who attended all follow-up appointments vs. patients who prematurely discontinued follow-up after arthroscopic rotator cuff repair. Better communication with patients in the postoperative period may help to improve follow-up after arthroscopic rotator cuff repair.

Efficacy of transdermal 4% lidocaine patches for postoperative pain management after arthroscopic rotator cuff repair: a prospective trial.

BACKGROUND: Postoperative pain management continues to be a challenging aspect of patient care. Lidocaine patches have shown efficacy in reducing pain in other surgical specialties and mixed results in orthopedic trials. We sought to determine the effectiveness of nonprescription lidocaine patches in reducing postoperative pain after arthroscopic rotator cuff repair. METHODS: Patients undergoing primary arthroscopic rotator cuff repair were recruited from 3 surgeons at a single institution. All patients of each surgeon were randomized to a lidocaine patch or control group, with crossover occurring at the midpoint. Experimental group patients received 26 4% lidocaine gel-patches. They were provided written and visual instructions to begin wearing the lidocaine patches during daytime on postoperative day (POD) 2. They were to be switched every 8 hours and removed overnight. Control group patients received normal standard of care but did not receive a placebo control. Exclusion criteria included workmen's compensation claims, age <18 years, history of myocardial infarction, and history of lidocaine or adhesive allergies. The American Shoulder and Elbow Surgeons shoulder survey was completed preoperatively and 2-, 6-weeks, 3-, 4.5-, and 6-months postoperatively. A 14-day visual analog scale pain and medication log was completed three times daily following repair. All patients received interscalene nerve block with bupivacaine and general anesthesia. RESULTS: 80 (40 control, 40 lidocaine) patients were enrolled, with 53 completing follow-up. Groups were demographically similar in age (P = .22), gender (P = .20), and body mass index (P = .77). They were similar in tear pattern (P = .95), concomitant acromioplasty (P = .44), concomitant biceps tenodesis (P = .07), and number of anchors used (P = .25). There was no difference in American Shoulder and Elbow Surgeons scores at any time points (range P = .28-P = .97). Reported 14-day pain logs were not different between study groups at any time points (range P = .07-P = .99). There was no difference in opioid consumption in the first 14 days after surgery (P = .38). The lidocaine group reported less satisfaction with their pain management beginning in the evening of POD 2 (P = .05). This continued until the afternoon of POD 8 (P = .03). CONCLUSION: Transdermal 4% lidocaine patches are not effective in reducing pain or opioid consumption after arthroscopic rotator cuff repair and were associated with reduced patient satisfaction.

Comparison of technical errors in pediatric bitewing radiographs acquired with round vs rectangular collimation.

OBJECTIVE: To compare technical errors in bitewing radiographs acquired with round vs rectangular collimation in a hospital-based pediatric dentistry training program. STUDY DESIGN: A retrospective chart review was conducted of 176 digital bitewing radiographs exposed with round collimation and 106 exposed with rectangular collimation. The number of re-exposures was calculated, and errors in central ray entry (CRE; "cone cuts"), horizontal and vertical positioning, and angulation were measured. RESULTS: There were no greater re-exposures but significantly more CRE errors with rectangular collimation (21.7%; n = 23; 95% confidence interval [CI], 13.9%-30.0%) than with round collimation (3.4%; n = 6; 95% CI, 0.7%-6.1%). CRE error location, horizontal positioning errors, and size of horizontal overlapped contacts were statistically different but not clinically important. CONCLUSIONS: Use of rectangular collimation resulted in increased CRE errors but no other clinically significant problems. This technique should be used to reduce radiation exposure to patients.

Do Relaxation Exercises Decrease Pain After Arthroscopic Rotator Cuff Repair? A Randomized Controlled Trial.

BACKGROUND: Pain after rotator cuff repair is commonly managed with opioid medications; however, these medications are associated with serious adverse effects. Relaxation exercises represent a potential nonpharmacologic method of pain management that can be easily implemented without substantial adverse effects; however, the effects of relaxation exercises have not been studied in a practical, reproducible protocol after arthroscopic rotator cuff repair. QUESTIONS/PURPOSES: (1) Does performing relaxation exercises after arthroscopic rotator cuff repair (ARCR) decrease pain compared with standard pain management medication? (2) Does performing relaxation exercises after ARCR decrease opioid consumption? (3) What proportion of patients who used the relaxation techniques believed they decreased their pain level, and what proportion continued using these techniques at 2 weeks? (4) Does performing relaxation exercises after ARCR affect shoulder function? METHODS: During the study period, 563 patients were eligible for inclusion; however, only 146 were enrolled, randomized, and postoperatively followed (relaxation group: 74, control group: 72); 68% (384 of 563) of patients were not contacted due to patient and research staff availability. Thirty-three patients were unenrolled preoperatively or immediately postoperatively due to change in operative procedure (such as, only debridement) or patient request; no postoperative data were collected from these patients. Follow-up proportions were similar between the relaxation and control groups (relaxation: 80%, control: 81%; p = 0.90). The relaxation group received and reviewed educational materials consisting of a 5-minute video and an educational pamphlet explaining relaxation breathing techniques, while the control group did not receive relaxation education materials. Patients recorded their pain levels and opioid consumption during the 5 days after ARCR. Patients also completed the American Shoulder and Elbow Surgeons shoulder score preoperatively and 2, 6, 13, 18, and 26 weeks postoperatively. Linear mixed models were created to analyze postoperative pain, opioid consumption measured in morphine milligram equivalents (MMEs), and shoulder function outcomes. A per-protocol approach was used to correct for patients who were enrolled but subsequently underwent other procedures. RESULTS: There was no difference in pain scores between the relaxation and control groups during the first 5 days postoperatively. There was no difference in pain scores at 2 weeks postoperatively between the relaxation and control groups (3.3 ± 3 versus 3.5 ± 2, mean difference -0.22 [95% CI -1.06 to 0.62]; p = 0.60). There was no difference in opioid consumption during the first 5 days postoperatively between the relaxation and control groups. The use of relaxation exercises resulted in lower 2-week narcotics consumption in the relaxation group than in the control group (309 ± 241 MMEs versus 442 ± 307 MMEs, mean difference -133 [95% CI -225 to -42]; p < 0.01). Sixty-two percent (41 of 66) of patients in the relaxation group believed the relaxation exercises decreased their pain levels. Fifty-two percent (34 of 66) were still performing the exercises at 2 weeks postoperatively. During the 6-month follow-up period, there was no difference in shoulder function between the relaxation and control groups. CONCLUSION: The preoperative administration of quick, basic relaxation exercises allowed patients to use appreciably lower opioid analgesic doses over the first 2 weeks after ARCR, without any worsening of pain scores. We consider this result promising but preliminary; it is possible that a more intense mindfulness intervention-the one we studied here was disseminated using only a 5-minute video-would deliver reductions in pain and further reductions in opioid usage. LEVEL OF EVIDENCE: Level II, therapeutic study.

First quantitative assessment of the adsorption of a fluorocarbon gas on phospholipid monolayers at the air/water interface.

HYPOTHESIS: Fluorocarbon gases introduced above monolayers of phospholipids at the air/water interface were recently found to promote the adsorption of diverse molecular compounds, with potential application in drug-loaded microbubble design. Quantitative determination of the fluorocarbon present in the monolayers is strongly needed for the development of such applications. We hypothesized that neutron reflectometry (NR) and ellipsometry experiments would allow quantification of the fluorocarbon trapped in the monolayers. EXPERIMENTS: We report the first quantitative determination of the extents of adsorption of perfluorohexane (F-hexane) on different phospholipid monolayers with respect to both their phase and isotopic form. To this aim, we applied an approach based on co-modeling the data obtained from NR and ellipsometry. FINDINGS: We found that F-hexane adsorbs strongly in monolayers of dipalmitoylphosphatidylcholine (DPPC) when they are both in the liquid expanded (LE) and liquid condensed (LC) phases, but to different extents according to the isotopic form of the phospholipid. Kinetic resolution of the interfacial composition from data on both isotopic contrasts (assuming chemical identicality) was therefore not possible using NR alone, so an alternative NR/ellipsometry co-modeling treatment was applied to data from each isotopic contrast. F-hexane adsorbs more abundantly on monolayers of hydrogenous DPPC than chain-deuterated DPPC when they are in the LE phase, whilst the opposite was observed when they monolayers are in the LC phase. The extents of adsorption of F-hexane in monolayers of dimyristoylphosphatidylcholine (DMPC, LE phase) and distearoylphosphatidylcholine (DSPC, LC phase) concurs with the strong dependence of those with phospholipids of different isotopic contrasts according to the monolayer phase. This new methodology can lead to advances in the novel characterization of fluorocarbons interacting with phospholipid monolayers of relevance to applications such as in the shells of fluorocarbon-stabilized medically-oriented microbubbles.

Interactions of anticancer drugs doxorubicin and idarubicin with lipid monolayers: New insight into the composition, structure and morphology.

We quantify directly here for the first time the extents of interactions of two different anthracycline drugs with pure and mixed lipid monolayers with respect to the surface pressure and elucidate differences in the resulting interaction mechanisms. The work concerns interactions of doxorubicin (DOx) and idarubicin (IDA) with monolayers of the zwitterionic DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) and negatively charged DMPS (1,2-dimyristoyl-sn-glycero-3-phospho-L-serine (sodium salt)) as well as a 7:3 mixture of the two lipids. These drugs are used in current cancer treatments, while the lipid systems were chosen as phosphocholines are the major lipid component of healthy cell membranes, and phosphoserines are the major lipid component that is externalized into the outer leaflet of cancerous cell membranes. It is shown that DOx interacts with DMPS monolayers to a greater extent than with DMPC monolayers by lower limits of a factor of 5 at a surface pressure of 10 mN/m and a factor of 12 at 30 mN/m. With increasing surface pressure, the small amount of drug (~0.3 µmol/m2) bound to DMPC monolayers is excluded from the interface, yet its interaction with DMPS monolayers is enhanced until there is even more drug (~3.2 µmol/m2) than lipid (~2.6 µmol/m2) at the interface. Direct evidence is presented for all systems studied that upon surface area compression lipid is reproducibly expelled from the monolayer, which we infer to be in the form of drug-lipid aggregates, yet the nature of adsorption of material back to the monolayer upon expansion is system-dependent. At 30 mN/m, most relevant to human physiology, the interactions of DOx and IDA are starkly different. For DOx, there is a conformational change in the interfacial layer driven by aggregation, resulting in the formation of lateral domains that have extended layers of drug. For the more lipophilic IDA, there is penetration of the drug into the hydrophobic acyl chain region of the monolayer and no indication of lateral segregation. In addition to the Langmuir technique, these advances were made as a result of direct measurements of the interfacial composition, structure and morphology using two different implementations of neutron reflectometry and Brewster angle microscopy. The results provide new insight into key processes that determine the uptake of drugs such as limited drug penetration through cell membranes by passive diffusion as well as activation of drug removal mechanisms related to multidrug resistance.

The reaction of oleic acid monolayers with gas-phase ozone at the air water interface: the effect of sub-phase viscosity, and inert secondary components.

Organic films that form on atmospheric particulate matter change the optical and cloud condensation nucleation properties of the particulate matter and consequently have implications for modern climate and climate models. The organic films are subject to attack from gas-phase oxidants present in ambient air. Here we revisit in greater detail the oxidation of a monolayer of oleic acid by gas-phase ozone at the air-water interface as this provides a model system for the oxidation reactions that occur at the air-water interface of aqueous atmospheric aerosol. Experiments were performed on monolayers of oleic acid at the air-liquid interface at atmospherically relevant ozone concentrations to investigate if the viscosity of the sub-phase influences the rate of the reaction and to determine the effect of the presence of a second component within the monolayer, stearic acid, which is generally considered to be non-reactive towards ozone, on the reaction kinetics as determined by neutron reflectometry measurements. Atmospheric aerosol can be extremely viscous. The kinetics of the reaction were found to be independent of the viscosity of the sub-phase below the monolayer over a range of moderate viscosities, , demonstrating no involvement of aqueous sub-phase oxidants in the rate determining step. The kinetics of oxidation of monolayers of pure oleic acid were found to depend on the surface coverage with different behaviour observed above and below a surface coverage of oleic acid of ∼1 × 1018 molecule m-2. Atmospheric aerosol are typically complex mixtures, and the presence of an additional compound in the monolayer that is inert to direct ozone oxidation, stearic acid, did not significantly change the reaction kinetics. It is demonstrated that oleic acid monolayers at the air-water interface do not leave any detectable material at the air-water interface, contradicting the previous work published in this journal which the authors now believe to be erroneous. The combined results presented here indicate that the kinetics, and thus the atmospheric chemical lifetime for unsaturated surface active materials at the air-water interface to loss by reaction with gas-phase ozone, can be considered to be independent of other materials present at either the air-water interface or in the aqueous sub-phase.

Manufacturing drug co-loaded liposomal formulations targeting breast cancer: Influence of preparative method on liposomes characteristics and in vitro toxicity.

Developing more efficient manufacturing methods for nano therapeutic systems is becoming important, not only to better control their physico-chemical characteristics and therapeutic efficacy but also to ensure scale-up is cost-effective. The principle of cross-flow chemistry allows precise control over manufacturing parameters for the fabrication of uniform liposomal formulations, as well as providing reproducible manufacturing scale-up compared to conventional methods. We have herein investigated the use of microfluidics to produce PEGylated DSPC liposomes loaded with doxorubicin and compared their performance against identical formulations prepared by the thin-film method. The isoprenylated coumarin umbelliprenin was selected as a co-therapeutic. Umbelliprenin-loaded and doxorubicin:umbelliprenin co-loaded liposomes were fabricated using the optimised microfluidic set-up. The role of umbelliprenin as lipid bilayer fluidity modulation was characterized, and we investigated its role on liposomes size, size distribution, shape and stability compared to doxorubicin-loaded liposomes. Finally, the toxicity of all liposomal formulations was tested on a panel of human breast cancer cells (MCF-7, MDA-MB 231, BT-474) to identify the most potent formulation by liposomal fabrication method and loaded compound(s). We herein show that the microfluidic system is an alternative method to produce doxorubicin:umbelliprenin co-loaded liposomes, allowing fine control over liposome size (100-250 nm), shape, uniformity and doxorubicin drug loading (>80%). Umbelliprenin was shown to confer fluidity to model lipid biomembranes, which helps to explain the more homogeneous size and shape of co-loaded liposomes compared to liposomes without umbelliprenin. The toxicity of doxorubicin:umbelliprenin co-loaded liposomes was lower than that of free doxorubicin, due to the delayed release of doxorubicin from liposomes. An alternative, rapid and easy manufacturing method for the production of liposomes has been established using microfluidics to effectively produce uniform doxorubicin:umbelliprenin co-loaded liposomal formulations with proven cytotoxicity in human breast cancer cell lines in vitro.

Spatial access to primary care providers and colorectal cancer-specific survival in Cook County, Illinois.

BACKGROUND: Spatial access to primary care has been associated with late-stage and fatal breast cancer, but less is known about its relation to outcomes of other screening-preventable cancers such as colorectal cancer. This population-based retrospective cohort study examined whether spatial access to primary care providers associates with colorectal cancer-specific survival. METHODS: Approximately 26 600 incident colorectal cancers diagnosed between 2000 and 2008 in adults residing in Cook County, Illinois were identified through the state cancer registry and georeferenced to the census tract of residence at diagnosis. An enhanced two-step floating catchment area method measured tract-level access to primary care physicians (PCPs) in the year of diagnosis using practice locations obtained from the American Medical Association. Vital status and underlying cause of death were determined using the National Death Index. Fine-Gray proportional subdistribution hazard models analyzed the association between tract-level PCP access scores and colorectal cancer-specific survival after accounting for tract-level socioeconomic status, case demographics, tumor characteristics, and other factors. RESULTS: Increased tract-level access to PCPs was associated with a lower risk of death from colorectal cancer (hazard ratio [HR], 95% confidence interval [CI]) = 0.87 [0.79, 0.96], P = .008, highest vs lowest quintile), especially among persons diagnosed with regional-stage tumors (HR, 95% CI = 0.80 [0.69, 0.93], P = .004, highest vs lowest quintile). CONCLUSIONS: Spatial access to primary care providers is a predictor of colorectal cancer-specific survival in Cook County, Illinois. Future research is needed to determine which areas within the cancer care continuum are most affected by spatial accessibility to primary care such as referral for screening, accessibility of screening and diagnostic testing, referral for treatment, and access to appropriate survivorship-related care.

A survey on radiation exposure reduction methods including rectangular collimation for intraoral radiography by pediatric dentists in the United States.

BACKGROUND: The authors conducted a survey of the American Academy of Pediatric Dentistry (AAPD) to determine awareness of the Image Gently Campaign in Dentistry (IGCD) and to ascertain radiologic practices, including radiation dose-reduction strategies such as rectangular collimation. METHODS: An institutional review board approved an electronic survey sent to 7,087 AAPD members covering practitioner demographic characteristics, radiographic techniques, and dose-reduction practices, including rectangular collimation. Responses were tabulated and analyzed using binomial tests, χ2 tests, and Fisher exact tests. RESULTS: A total of 1,124 pediatric dentists or residents in pediatric dentistry responded, (response rate 16%, margin of error ± 2.7%). The largest group (23.8%) graduated after 2010. More than 90% indicated that they followed American Dental Association (ADA)-AAPD radiation exposure guidelines, but only 33.5% were aware of IGCD. Almost all respondents used direct digital systems, storage phosphor plates, or both. Only 22.3% (n = 220) used rectangular collimation. Nonusers indicated that they were unfamiliar with collimation (33.3%) or concerned about potential for increased cone cuts (30.2%), 11.6% of respondents were unaware of any regulatory requirements for inspections of radiographic equipment recurring at regular intervals, and 4.1% of respondents considered use of lead aprons optional. CONCLUSIONS: Although the pediatric dentists surveyed believe they are in compliance with ADA-AAPD guidelines, most are unaware of IGCD recommendations. Use of digital radiography is almost ubiquitous, but use of rectangular collimation is limited. PRACTICE IMPLICATIONS: Dentists treating children should be familiar with ADA-AAPD radiation exposure guidelines and should consider using the dose-reduction strategies recommended by IGCD.