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1.
J Am Chem Soc ; 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39001844

ABSTRACT

The utility of antibody therapeutics is hampered by potential cross-reactivity with healthy tissue. Over the past decade, significant advances have been made in the design of activatable antibodies, which increase, or create altogether, the therapeutic window of a parent antibody. Of these, antibody prodrugs (pro-antibodies) are masked antibodies that have advanced the most for therapeutic use. They are designed to reveal the active, parent antibody only when encountering proteases upregulated in the microenvironment of the targeted disease tissue, thereby minimizing off-target activity. However, current pro-antibody designs are relegated to fusion proteins that append masking groups restricted to the use of only canonical amino acids, offering excellent control of the site of introduction, but with no authority over where the masking group is installed other than the N-terminus of the antibody. Here, we present a palladium-based bioconjugation approach for the site-specific introduction of a masked tyrosine mimic in the complementary determining region of the FDA approved antibody therapeutic ipilimumab used as a model system. The approach enables the introduction of a protease cleavable group tethered to noncanonical polymers (polyethylene glycol (PEG)) resulting in 47-fold weaker binding to cells expressing CTLA-4, the target antigen of ipilimumab. Upon exposure to tumor-associated proteases, the masking group is cleaved, unveiling a tyrosine-mimic (dubbed hydroxyphenyl cysteine (HPC)) that restores (>90% restoration) binding affinity to its target antigen.

2.
Article in English | MEDLINE | ID: mdl-38981101

ABSTRACT

Organometallic molecules are promising for molecular electronic devices due to their potential to improve electrical conductance through access to complex orbital covalency that is not available to light-element organic molecules. However, studies of the formation of organometallic monolayers and their charge transport properties are scarce. Here, we report the cluster formation and charge transport properties of gold-triarylbismuthane-gold molecular junctions. We found that triarylbismuthane molecules with -CN anchoring groups form clusters during the creation of self-assembled submonolayers. This clustering is attributed to strong interactions between the bismuth (Bi) center and the nitrogen atom in the -CN group of adjacent molecules. Examination of the influence of -NH2 and -CN anchoring groups on junction conductance revealed that, despite a stronger binding energy between the -NH2 group and gold, the conductance per molecular unit (i.e., molecule for the -NH2 group and cluster for the -CN group) is higher with the -CN anchoring group. Further analysis showed that an increase in the number of -CN groups from one to three within the junctions leads to a decrease in conductance while increasing the size of the cluster. This demonstrates the significant effects of different anchoring groups and the impact of varying the number of -CN groups on both the charge transport and cluster formation. This study highlights the importance of selecting the appropriate anchoring group in the design of molecular junctions. Additionally, controlling the size and formation of clusters can be a strategic approach to engineering charge transport in molecular junctions.

3.
Ann Plast Surg ; 92(6S Suppl 4): S408-S412, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38857005

ABSTRACT

INTRODUCTION: The healthcare costs for treatment of community-acquired decubitus ulcers accounts for $11.6 billion in the United States annually. Patients with stage 3 and 4 decubitus ulcers are often treated inefficiently prior to reconstructive surgery while physicians attempt to optimize their condition (debridement, fecal/urinary diversion, physical therapy, nutrition, and obtaining durable medical goods). We hypothesized that hospital costs for inpatient optimization of decubitus ulcers would significantly differ from outpatient optimization costs, resulting in significant financial losses to the hospital and that transitioning optimization to an outpatient setting could reduce both total and hospital expenditures. In this study, we analyzed and compared the financial expenditures of optimizing patients with decubitus ulcers in an inpatient setting versus maximizing outpatient utilization of resources prior to reconstruction. METHODS: Encounters of patients with stage 3 or 4 decubitus ulcers over a 5-year period were investigated. These encounters were divided into two groups: Group 1 included patients who were optimized totally inpatient prior to reconstructive surgery; group 2 included patients who were mostly optimized in an outpatient setting and this encounter was a planned admission for their reconstructive surgery. Demographics, comorbidities, paralysis status, and insurance carriers were collected for all patients. Financial charges and reimbursements were compared among the groups. RESULTS: Forty-five encounters met criteria for inclusion. Group 1's average hospital charges were $500,917, while group 2's charges were $134,419. The cost of outpatient therapeutic items for patient optimization prior to wound closure was estimated to be $10,202 monthly. When including an additional debridement admission for group 2 patients (average of $108,031), the maximal charges for total care was $252,652, and hospital reimbursements were similar between group 1 and group 2 ($65,401 vs $50,860 respectively). CONCLUSIONS: The data derived from this investigation strongly suggests that optimizing patients in an outpatient setting prior to decubitus wound closure versus managing the patients totally on an inpatient basis will significantly reduce hospital charges, and hence costs, while minimally affecting reimbursements to the hospital.


Subject(s)
Pressure Ulcer , Humans , Pressure Ulcer/economics , Pressure Ulcer/therapy , Pressure Ulcer/surgery , Male , Female , Middle Aged , Aged , Ambulatory Care/economics , Retrospective Studies , United States , Health Care Costs/statistics & numerical data , Hospital Costs/statistics & numerical data , Hospitalization/economics , Plastic Surgery Procedures/economics , Plastic Surgery Procedures/methods , Quality Improvement/economics , Adult , Aged, 80 and over
4.
Am J Emerg Med ; 78: 112-119, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38244244

ABSTRACT

OBJECTIVES: In the Emergency Department (ED), ultrasound-guided nerve blocks (UGNBs) have become a cornerstone of multimodal pain regimens. We investigated current national practices of UGNBs across academic medical center EDs, and how these trends have changed over time. METHODS: We conducted a cross-sectional electronic survey of academic EDs with ultrasound fellowships across the United States. Twenty-item questionnaires exploring UGNB practice patterns, training, and complications were distributed between November 2021-June 2022. Data was manually curated, and descriptive statistics were performed. The survey results were then compared to results from Amini et al. 2016 UGNB survey to identify trends. RESULTS: The response rate was 80.5% (87 of 108 programs). One hundred percent of responding programs perform UGNB at their institutions, with 29% (95% confidence interval (CI), 20%-39%) performing at least 5 blocks monthly. Forearm UGNB are most commonly performed (96% of programs (95% CI, 93%-100%)). Pain control for fractures is the most common indication (84%; 95% CI, 76%-91%). Eighty-five percent (95% CI, 77%-92%) of programs report at least 80% of UGNB performed are effective. Eighty-five percent (95% CI, 66%-85%) of programs have had no reported complications from UGNB performed by emergency providers at their institution. The remaining 15% (95% CI, 8%-23%) report an average of 1 complication annually. CONCLUSIONS: All programs participating in our study report performing UGNB in their ED, which is a 16% increase over the last 5 years. UGNB's are currently performed safely and effectively in the ED, however practice improvements can still be made. Creating multi-disciplinary committees at local and national levels can standardize guidelines and practice policies to optimize patient safety and outcomes.


Subject(s)
Emergency Medicine , Nerve Block , Humans , United States , Cross-Sectional Studies , Nerve Block/methods , Ultrasonography , Emergency Service, Hospital , Pain , Ultrasonography, Interventional/methods
5.
Foot Ankle Spec ; : 19386400231226028, 2024 Jan 28.
Article in English | MEDLINE | ID: mdl-38282326

ABSTRACT

BACKGROUND: Parallax is an imaging phenomenon where an object appears to be at different positions when viewed from different angles. Distortion can occur secondary to internal fluoroscopic, or external environmental, factors. Fluoroscopy is a vital tool to assist surgeons intraoperatively. However, parallax and distortion can lead to inaccuracy, potentially leading to incorrect surgical decisions. The purpose of this study was to investigate the prevalence of parallax/distortion in large fluoroscopy units at a level-1 trauma center. METHODS: Two types of C-arm models were evaluated, including (1) round image intensifiers, and (2) flat plate detectors (FPD). A square plexiglass grid with embedded wire at ½-in intervals was created, with a round metal washer secured centrally. The grid was placed 16 in from the image intensifier. A metal ball bearing (BB) was secured to the center of the x-ray tube. Fluoroscopic images were obtained until the BB and washer were "center-center." A straight blade served as a fiducial marker to ensure there was no off-axis angulation. Standard anterior-posterior and lateral views were obtained. External factors were considered, tested, and limited. Images were printed and the patterns of parallax/distortion were identified. RESULTS: All 11/11 (100%) of fluoroscopy units had some degree of parallax and/or distortion. We noted 3 different patterns, including sigmoidal, converging, and diverging. The FPD units had less apparent distortion overall; however, two-thirds (66%) were off-axis in the x- and y-axes in relation to the fiducial marker. CONCLUSION: All fluoroscopy units had varying degrees and patterns of parallax/distortion. We noted less overall distortion in FPDs. However, some of these units may produce images that are off-axis. This research has important implications for improving the accuracy of intraoperative fluoroscopy. Musculoskeletal surgeons should understand the limitations of fluoroscopy and how to combat parallax distortion to improve surgical outcomes and reduce patient morbidity. LEVEL OF EVIDENCE: Level V.

7.
Langmuir ; 39(11): 3853-3861, 2023 Mar 21.
Article in English | MEDLINE | ID: mdl-36893476

ABSTRACT

Magnesium diboride (MgB2) has demonstrated, theoretically and experimentally, promise as a candidate material for hydrogen storage and has thus attracted much contemporary research interest. To study hydrogen gas adsorption on MgB2 thin films using a quartz crystal microbalance (QCM)─a workhorse apparatus for this specific experiment─MgB2 must be deposited uniformly on the active surface of the QCM without damaging the quartz's performance. In work presented here, a wet-chemistry colloid synthesis and deposition process of a MgB2 thin film on a gold (Au) surface was established to avoid the extreme conditions of conventional physical deposition methods. This process also counteracts the unwanted phenomena of drying droplets on a solid surface, particularly the coffee-ring effect. To verify the normal function of the QCM after MgB2 deposition and its ability to obtain meaningful data, simple gas adsorption tests were conducted on the QCM, and the MgB2 film on the QCM was characterized with X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) for elemental analysis and surface roughness, respectively. To obtain information about the thickness and the involvement of the coffee-ring effect, the same synthesis route was applied on a similar gold substrate─an evaporated Au film on glass. XPS characterization of the film and its precursor suspension shows the potential existence of both MgB2 and its oxide forms. The film's thickness on evaporated Au was measured by scanning transmission electron microscopy (STEM) to be 3.9 nm. The resulting samples show mitigation of the coffee-ring effect through roughness measurements with AFM at two scan sizes of 50 × 50 and 1 × 1 µm2.

8.
ACS Chem Biol ; 18(3): 518-527, 2023 03 17.
Article in English | MEDLINE | ID: mdl-36821521

ABSTRACT

The impermeable outer membrane of Pseudomonas aeruginosa is bypassed by antibacterial proteins known as S-type pyocins. Because of their properties, pyocins are investigated as a potential new class of antimicrobials against Pseudomonas infections. Their production and modification, however, remain challenging. To address this limitation, we employed automated fast-flow peptide synthesis for the rapid production of a pyocin S2 import domain. The N-terminal domain sequence (PyS2NTD) was synthesized in under 10 h and purified to yield milligram quantities of the desired product. To our knowledge, the 214 amino acid sequence of PyS2NTD is among the longest peptides produced from a "single-shot" synthesis, i.e., made in a single stepwise route without the use of ligation techniques. Biophysical characterization of the PyS2NTD with circular dichroism was consistent with the literature reports. Fluorescently labeled PyS2NTD binds to P. aeruginosa expressing the cognate ferripyoverdine receptor and is taken up into the periplasm. This selective uptake was validated with confocal and super resolution microscopy, flow cytometry, and fluorescence recovery after photobleaching. These modified, synthetic S-type pyocin domains can be used to probe import mechanisms of P. aeruginosa and leveraged to develop selective antimicrobial agents that bypass the outer membrane.


Subject(s)
Anti-Infective Agents , Pyocins , Pyocins/chemistry , Pyocins/metabolism , Amino Acids , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Amino Acid Sequence , Pseudomonas aeruginosa/metabolism
9.
Phys Chem Chem Phys ; 25(5): 4255-4265, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36683432

ABSTRACT

Hydrogen storage materials form a crucial research topic for future energy utilization employing hydrogen and among those of interest magnesium diboride (MgB2) has shown its prevalence. In this study, a first-principles analytical adsorption model of one hydrogen molecule in the vicinity of various magnesium diboride crystal surfaces was developed in order to obtain surface thermodynamic properties as a function of molecular and lattice properties. Henry's law constant (KH) and isosteric heat of adsorption (ΔHads) indicators of the affinity between a gaseous molecule and a solid surface are thus calculated. The results in this paper not only address questions pertaining to the first stage of hydrogen storage processes but also advance the understanding of physisorption thermodynamics of a neutral molecule (H2) coming in contact with a layered metallic-like surface (MgB2). Although the model is built from a framework of classical calculations, quantum effects are incorporated as the fractional charge of the ions on the free surfaces, which is essential for the calculation of analytic thermodynamic values that approximate calculations from other methods. To benchmark our theoretical models, periodic density functional calculations were performed to determine the interactions between H2 and different MgB2 surfaces from first-principles. By considering both the top and sublayers of MgB2 in calculating interaction energy, we have analytically and computationally calculated the interaction energies of H2 molecules and MgB2's terminated planes, and witnessed the strong dependence of interaction energies on surface charges. We have also observed a dipole flipping phenomenon which explains the discontinuity seen in the interaction energy graph of Mg(0001). Both analytical and computational results showed heat of adsorption at zero coverage varying at a very low range (<7 kJ mol-1).

10.
J Cancer Educ ; 38(1): 301-308, 2023 02.
Article in English | MEDLINE | ID: mdl-34767182

ABSTRACT

The current study evaluated formal training around spiritual care for healthcare providers and the relationships between that training, perceived barriers to spiritual care, and frequency of inquiry around spiritual topics. A mixed methods explanatory sequential design was used. Quantitative methods included an online survey administered to providers at The Ohio State University Comprehensive Cancer Center. Main and interactive effects of formal training and barriers to spiritual care on frequency of inquiry around spiritual topics were assessed with two-way ANOVA. Qualitative follow-up explored provider strategies to engage spiritual topics. Among 340 quantitative participants, most were female (82.1%) or White (82.6%) with over one-half identifying as religious (57.5%). The majority were nurses (64.7%) and less than 10% of all providers (n = 26) indicated formal training around spiritual care. There were main effects on frequency of inquiry around spiritual topics for providers who indicated "personal discomfort" as a barrier (p < 0.001), but not formal training (p = 0.526). Providers who indicated "personal discomfort" as a barrier inquired about spirituality less frequently, regardless of receiving formal training (M = 8.0, SD = 1.41) or not (M = 8.76, SD = 2.96). There were no interactive effects between training and "may offend patients" or "personal discomfort" (p = 0.258 and 0.125, respectively). Qualitative analysis revealed four strategies with direct and indirect approaches: (1) permission-giving, (2) self-awareness/use-of-self, (3) formal assessment, and (4) informal assessment. Training for providers should emphasize self-awareness to address intrapersonal barriers to improve the frequency and quality of spiritual care for cancer patients.


Subject(s)
Spiritual Therapies , Spirituality , Humans , Female , Male , Health Personnel/education , Surveys and Questionnaires , Ohio
11.
J Occup Environ Hyg ; 20(2): 55-83, 2023 02.
Article in English | MEDLINE | ID: mdl-36459063

ABSTRACT

California's Office of Environmental Health Hazard Assessment has updated the comprehensive age-specific model of lead metabolism in humans published by Richard W. Leggett in 1993. The updated model, called Leggett+, was introduced in a peer-reviewed report in 2013. The Leggett + model simulates the relationship between blood lead and exposure in the workplace. Leggett + includes a workplace exposure model comprising respiratory tract intake (workplace lead inhaled by a worker) and uptake (lead absorbed into the blood from the respiratory tract plus uptake from ambient air and diet). The latter is calculated as intake times an inhalation transfer coefficient plus background uptake. An adjusted adult systemic model describes the metabolism of the absorbed lead. This paper provides details about the workplace exposure and uptake elements of Leggett+, an updated approach to calibrating an inhalation transfer coefficient, confirmation of the model's performance in predicting blood lead levels from workplace studies, and predictions of blood lead levels from simulated exposures to workplace airborne lead over a working lifetime. Blood lead relative to airborne lead concentrations in a standard workplace scenario predicted by Leggett + was similar to corresponding relationships from four published workplace studies. Leggett + predictions displayed a good fit to regression equations when other key factors were considered such as pre-employment blood lead and ongoing background intake of lead, workplace air concentration, lead aerosol characteristics, and worker activity levels. The comprehensive Leggett + model can simulate plausible workplace air-blood lead relationships from a broad range of worker exposures. The inhalation transfer coefficient of 0.30, derived from empirical data described in the 2013 report has been reexamined. The original estimate continues to represent a plausible mid-point for a coefficient derived from an expanded range of theoretical particle size distributions deposited in the upper and lower regions of the respiratory tract considering intake during sedentary and outdoor activity breathing scenarios. This coefficient is slightly lower than the value of 0.35 estimated for unknown forms of lead by Leggett in 1993.


Subject(s)
Inhalation Exposure , Lead , Adult , Humans , Lead/analysis , Inhalation Exposure/analysis , Workplace , Aerosols
12.
Mol Phylogenet Evol ; 178: 107652, 2023 01.
Article in English | MEDLINE | ID: mdl-36306994

ABSTRACT

Molecular dating has been widely used to infer the times of past evolutionary events using molecular sequences. This paper describes three bootstrap methods to infer confidence intervals under a penalized likelihood framework. The basic idea is to use data pseudoreplicates to infer uncertainty in the branch lengths of a phylogeny reconstructed with molecular sequences. The three specific bootstrap methods are nonparametric (direct tree bootstrapping), semiparametric (rate smoothing), and parametric (Poisson simulation). Our extensive simulation study showed that the three methods perform generally well under a simple strict clock model of molecular evolution; however, the results were less positive with data simulated using an uncorrelated or a correlated relaxed clock model. Several factors impacted, possibly in interaction, the performance of the confidence intervals. Increasing the number of calibration points had a positive effect, as well as increasing the sequence length or the number of sequences although both latter effects depended on the model of evolution. A case study is presented with a molecular phylogeny of the Felidae (Mammalia: Carnivora). A comparison was made with a Bayesian analysis: the results were very close in terms of confidence intervals and there was no marked tendency for an approach to produce younger or older bounds compared to the other.


Subject(s)
Evolution, Molecular , Models, Genetic , Phylogeny , Bayes Theorem , Confidence Intervals
13.
Clin Pract Cases Emerg Med ; 6(4): 276-279, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36427038

ABSTRACT

INTRODUCTION: Pain scales are often used in peripheral nerve block studies but are problematic due to their subjective nature. Ultrasound-measured diaphragmatic excursion is an easily learned technique that could provide a much-needed objective measure of pain control over time with serial measurements. CASE SERIES: We describe three cases where diaphragmatic excursion was used as an objective measure of decreased pain and improved respiratory function after serratus anterior plane block in emergency department patients with anterior or lateral rib fractures. CONCLUSION: Diaphragmatic excursion may be an ideal alternative to pain scores to evaluate serratus anterior plane block efficacy. More data will be needed to determine whether this technique can be applied to other ultrasound-guided nerve blocks.

14.
Microorganisms ; 10(8)2022 Aug 16.
Article in English | MEDLINE | ID: mdl-36014071

ABSTRACT

We present observations from a laboratory-controlled study on the impacts of extreme wetting and drying on a wetland soil microbiome. Our approach was to experimentally challenge the soil microbiome to understand impacts on anaerobic carbon cycling processes as the system transitions from dryness to saturation and vice-versa. Specifically, we tested for impacts on stress responses related to shifts from wet to drought conditions. We used a combination of high-resolution data for small organic chemical compounds (metabolites) and biological (community structure based on 16S rRNA gene sequencing) features. Using a robust correlation-independent data approach, we further tested the predictive power of soil metabolites for the presence or absence of taxa. Here, we demonstrate that taking an untargeted, multidimensional data approach to the interpretation of metabolomics has the potential to indicate the causative pathways selecting for the observed bacterial community structure in soils.

15.
Rev Sci Instrum ; 93(6): 064105, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-35778017

ABSTRACT

The study of gas adsorption on a solid surface evaluates the affinity between sorbate gas and sorbent substrate and factors that contribute to this. This paper presents a test platform for adsorption experiments of various gases on various solid surfaces. Controlled environmental conditions enable investigations in materials surface science and increase the consistency among adsorption data. The system utilizes a quartz crystal microbalance to perform gravimetric analysis of deposition and adsorption, enabling investigation of the interaction of gaseous molecules with solid surfaces. In this study, a quartz crystal microbalance as gas adsorption detector was integrated with an environmental chamber to create a versatile tool for gas adsorption experiments on thin films. Experimental operation of this apparatus was demonstrated via acquisition of the adsorption isotherms of cyclohexane vapor on a gold surface at 55 and 70 °C. The result indicated International Union of Pure and Applied Chemistry Type II adsorption. Consequentially, application of the Brunauer-Emmett-Teller model to the isotherm data subject to predefined criteria for linear region selection yielded a surface area of the sorbent of 0.53 cm2 at 55 °C. From the monolayer region of the isotherms, the isosteric heat of adsorption of the cyclohexane vapor on gold was calculated to be 37 kJ mol-1.

16.
PLoS One ; 17(7): e0270798, 2022.
Article in English | MEDLINE | ID: mdl-35901080

ABSTRACT

Nutrient enrichment alters plant community structure and function at a global scale. Coastal plant systems are expected to experience increased rates of nitrogen and phosphorus deposition by 2100, caused mostly by anthropogenic activity. Despite high density of studies investigating connections between plant community structure and ecosystem function in response to nutrient addition, inconsistencies in system response based on the ecosystem in question calls for more detailed analyses of nutrient impacts on community organization and resulting productivity response. Here, we focus on nutrient addition impacts on community structure and organization as well as productivity of different lifeforms in a coastal grassland. We established long-term nutrient enrichment plots in 2015 consisting of control (C), nitrogen (N), phosphorus (P), and nitrogen + phosphorus (NP) treatments. In 2017 we collected graminoid and forb productivity, root productivity, and community composition for each plot. We found no N x P interaction, but N enrichment was a significant main effect on productivity, highlighting N limitation in coastal systems. Importantly, nutrient enrichment treatments did not alter root productivity. However, all treatments caused significant differences in community composition. Using rank abundance curves, we determined that community composition differences were driven by increased dominance of nitrophilous graminoids, re-organization of subordinate species, and species absences in N and NP plots. Results of this study highlight how coastal grassland communities are impacted by nutrient enrichment. We show that community re-organization, increased dominance, and absence of critical species are all important mechanisms that reflect community-level impacts of nutrient enrichment in our coastal grassland site.


Subject(s)
Ecosystem , Grassland , Nitrogen/analysis , Nutrients/analysis , Phosphorus/analysis , Plants , Soil/chemistry
17.
Med Vet Entomol ; 36(4): 456-468, 2022 12.
Article in English | MEDLINE | ID: mdl-35703533

ABSTRACT

Culicoides biting midges (Diptera: Ceratopogonidae) are biting nuisances and arbovirus vectors of both public health and veterinary significance in Trinidad. We compared sampling methods to define the behaviour and bionomics of adult Culicoides populations at a commercial dairy goat farm. Three static trap designs were compared: (a) Centre for Disease Control (CDC) downdraft UV trap; (b) CDC trap with an incandescent bulb and (c) CDC trap with semiochemical lure consisting of R-(-)-1-octen-3-ol and CO2 (no bulb). Sweep netting was used to define diel periodicity. A total of 30,701 biting midges were collected using static traps, dominated by female Culicoides furens (>70% of trap collections across all three designs). There was no significant difference in the Margalef's index between the three traps; however, trap designs A and C collected a significantly greater number of individuals than trap B, and trap C gained highest species richness. The greatest species richness and abundance of Culicoides collected by sweep net was observed between 6:00 and 6:15 pm and notable differences in the crepuscular activity pattern of several species were identified. Comparative data on Culicoides species richness, abundance, sex and reproductive status is discussed and can be used to improve surveillance strategies, research designs and risk management.


Subject(s)
Ceratopogonidae , Female , Animals , Trinidad and Tobago , Pheromones , Serogroup
19.
J Am Chem Soc ; 144(17): 7852-7860, 2022 05 04.
Article in English | MEDLINE | ID: mdl-35438502

ABSTRACT

Carboranes represent a class of compounds with increasing therapeutic potential. However, few general approaches to readily embed carboranes into small molecules, peptides, and proteins are available. We report a strategy based on palladium-mediated C-X (X = C, S, and N) bond formation for the installation of carborane-containing moieties onto small molecules and peptides. We demonstrate the ability of Pd-based reagents with appropriate ligands to overcome the high hydrophobicity of the carborane group and enable chemoselective conjugation of cysteine residues at room temperature in aqueous buffer. Accordingly, carboranes can be efficiently installed on proteins by employing a combination of a bis-sulfonated biarylphosphine-ligated Pd reagent in an aqueous histidine buffer. This method is successfully employed on nanobodies, a fully synthetic affibody, and the antibody therapeutics trastuzumab and cetuximab. The conjugates of the affibody ZHER2 and the trastuzumab antibody retained binding to their target antigens. Conjugated proteins maintain their activity in cell-based functional assays in HER2-positive BT-474 cell lines. This approach enables the rapid incorporation of carborane moieties into small molecules, peptides, and proteins for further exploration in boron neutron capture therapy, which requires the targeted delivery of boron-dense groups.


Subject(s)
Boranes , Palladium , Boranes/chemistry , Palladium/chemistry , Peptides , Proteins/chemistry , Trastuzumab
20.
Psychooncology ; 31(5): 705-716, 2022 05.
Article in English | MEDLINE | ID: mdl-35199401

ABSTRACT

OBJECTIVES: The objective of the current review was to synthesize the literature on intersectionality relative to disparities across the cancer care continuum. A model to support future intersectional cancer research was proposed. METHODS: Web-based discovery services and discipline-specific databases were queried for both peer-reviewed and gray literature. Study screening and data extraction were facilitated through the Covidence software platform. RESULTS: Among 497 screened studies, 28 met study inclusion criteria. Most articles were peer-reviewed empirical studies (n = 22) that focused on pre-diagnosis/screening (n = 19) and included marginalized racial/ethnic (n = 22) identities. Pre-cancer diagnosis, sexual orientation and race influenced women's screening and vaccine behaviors. Sexual minority women, particularly individuals of color, were less likely to engage in cancer prevention behaviors prior to diagnosis. Race and socioeconomic status (SES) were important factors in patient care/survivorship with worse outcomes among non-white women of low SES. Emergent themes in qualitative results emphasized the importance of patient intersectional identities, as well as feelings of marginalization, fears of discrimination, and general discomfort with providers as barriers to seeking cancer care. CONCLUSIONS: Patients with intersectional identities often experience barriers to cancer care that adversely impact screening, diagnosis, treatment, as well as survivorship. The use of an "intersectional lens" as a future clinical and research framework will facilitate a more multidimensional and holistic approach to the care of cancer patients.


Subject(s)
Neoplasms , Sexual and Gender Minorities , Female , Humans , Intersectional Framework , Male , Mass Screening , Neoplasms/therapy , Sexual Behavior
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