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BackgroundFunding agencies and researchers increasingly recognize the importance of patient stakeholder engagement in research. Despite calls for greater patient engagement, few studies have engaged a broad-based online community of patient stakeholders in the early stages of the research development process. ObjectiveThe objective of our study was to inform a research priority-setting agenda by using a Web-based survey to gather perceptions of important and difficult aspects of diabetes care from patient members of a social networking site-based community. MethodsInvitations to participate in a Web-based survey were sent by email to members of the PatientsLikeMe online diabetes community. The survey asked both quantitative and qualitative questions addressing individuals’ level of difficulty with diabetes care, provider communication, medication management, diet and exercise, and relationships with others. Qualitative responses were analyzed using content analysis. ResultsOf 6219 PatientsLikeMe members with diabetes who were sent survey invitations, 1044 (16.79%) opened the invitation and 320 (5.15% of 6219; 30.65% of 1044) completed the survey within 23 days. Of the 320 respondents, 33 (10.3%) reported having Type 1 diabetes; 107 (33.4%), Type 2 diabetes and taking insulin; and 180 (56.3%), Type 2 diabetes and taking oral agents or controlling their diabetes with lifestyle modifications. Compared to 2005-2010 National Health and Nutrition Examination Survey data for individuals with diabetes, our respondents were younger (mean age 55.8 years, SD 9.9 vs 59.4 years, SE 0.5); less likely to be male (111/320, 34.6% vs 48.4%); and less likely to be a racial or ethnic minority (40/312, 12.8% vs 37.5%). Of 29 potential challenges in diabetes care, 19 were categorized as difficult by 20% or more of respondents. Both quantitative and qualitative results indicated that top patient challenges were lifestyle concerns (diet, physical activity, weight, and stress) and interpersonal concerns (trying not to be a burden to others, getting support from family/friends). In our quantitative analysis, similar concerns were expressed across patient subgroups. ConclusionsLifestyle and interpersonal factors were particularly challenging for our online sample of adults with Type 1 or Type 2 diabetes. Our study demonstrates the innovative use of social networking sites and online communities to gather rapid, meaningful, and relevant patient perspectives that can be used to inform the development of research agendas.

BACKGROUND: Research shows the profound impact of social factors on health, lead many healths systems to incorporate social risk screening. To help healthcare systems select among various screening tools we compared two tools, the Your Current Life Situation (YCLS) and the Accountable Health Communities (AHC) Screening tools, on key psychometric properties. METHOD: Kaiser Permanente Southern California subsidized exchange members (n = 1008) were randomly invited to complete a survey containing either the YCLS or the AHC tool, as well as other measures related to care experience and health. Healthcare use was measured through the electronic health record. Agreement between the AHC and YCLS was assessed using adjusted kappas for six domains (food - worry, food - pay, insecure housing, housing quality, transportation, utilities). To assess predictive validity, items on the AHC and YCLS were compared to self-rated health and receipt of a flu shot. RESULTS: Responders (n = 450) and non-responders (n = 558) significantly differed on sex, language, and depression (P < 0.05) but not anxiety, race/ethnicity, or healthcare use. Agreement between the AHC and YCLS tools was substantial on all items (kappas > 0.60) except for housing quality (kappa 0.52). Four out of six screening questions on the AHC tool and four out of seven on the YCLS tool were associated with self-rated health (P < 0.03). No social needs were associated with flu shot receipt except utilities on the AHC tool (P = 0.028). CONCLUSION: In this sample, the AHC and YCLS tools are similar in their ability to screen for social risks. Differences observed likely stem from the timeframe and wording of the questions, which can be used to guide selection in healthcare systems.

The development of new radiopharmaceuticals for the detection of hidden infection foci has great relevance for early detection and the selection of the correct treatment, particularly in immunosuppressed patients. In that sense, the labelling of antimicrobial peptides (AMPs) that are capable of binding specifically to the pathogenic microorganism which causes the infection, should provide a sufficiently specific agent, able to distinguish an infection from a sterile inflammation. Defensins are particularly interesting molecules with antimicrobial activity, the EcgDf1 defensin was identified from the genome of a Uruguayan native plant, Erythrina crista‐galli, the 'Ceibo' tree. Our group has previously reported a synthetic biologically active short analogue EcgDf21 (ERFTGGHCRGFRRRCFCTKHC) successfully labelled with 99mTc. Herein we present a shorter analogue which also preserves the γ‐core domain, as a pharmacophore for a potential infection detection agent. This peptide was derivatized with the bifunctional chelating agent 1,4,7‐triazacyclononane‐1,4,7‐triacetic acid (NOTA) through a lysine linker in the amino‐terminal group (NOTA‐KGHCRGFRRRC) and radiolabelled with 68Ga ([68Ga]Ga‐NOTA‐K‐EcgDf1(10)). The [68Ga]Ga‐NOTA‐K‐EcgDf1(10) labelling procedure rendered a product with high radiochemical purity and stability in the labelling milieu. The Log P value indicated that the complex has a hydrophilic behaviour, confirmed by the biodistribution profile. The [68Ga]Ga‐NOTA‐K‐EcgDf1(10) complex demonstrated specific binding to cultures of Candida albicans and Aspergillus niger. Its biodistribution showed renal elimination and low accumulation in the rest of the body. It was possible to successfully differentiate sterile inflammation from infection by PET images in nude mice with a target/non‐target ratio of 3.3 for C. albicans and 3.7 for A. niger, respectively. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Adapting clinical care decisions for patient-reported social risks is essential to social health integration and patient-centered care. Most research in this area focuses on awareness and assistance (social-needs-targeted care), such as screening and referral to food, financial, and other resources. Limited evidence for adjustment strategies (social risk–informed care) or adapting care for social risks made it difficult for Kaiser Permanente to implement new initiatives. This article describes a codesign process to build a novel, adjustmentfocused continuing medical education course. METHODS: The authors codeveloped the online continuing medical education course with patients and clinicians using user-centered design. Transcripts from codesign activities were coded and analyzed by thematic analysis to identify major themes, including perceptions of social risk–informed care and barriers to care adjustment. RESULTS: Practical hurdles for implementing social risk–informed care emerged, including clinicians’ concerns about the ethics of adjustment as substandard care, particularly without robust assistance activities. However, patients expressed a desire for their care to be adapted to their social circumstances, to allow for more realistic care plans. DISCUSSION: Implementation barriers identified from the codesign were addressed through an interactive, case-study approach. Existing evidence on contextualized care and shared decision making informed a general framework for primary care providers to engage in awareness and adjustment activities, paired with 3 interactive case studies based on real-world, clinician-supplied scenarios. CONCLUSION: The authors recommend that multiple stakeholder perspectives be incorporated during the development of social health integration initiatives, particularly adjustment. Education complemented by active, nuanced, flexible implementation strategies may be necessary for the successful uptake of care-delivery-based social health integration activities. [ABSTRACT FROM AUTHOR]

Opportunistic infections are a problem of great relevance in public health and the precise detection and localization of infection in the early stages of the disease is of great importance for patient management as well as cost containment. Our proposal seeks to contribute to developing a new agent that meets the needs of diagnosis and follow‐up of fungal and bacterial infections, focused on the design of a radiotracer with the potential for recognition of hidden infection foci. Defensins are plant antimicrobial peptides that not only show activity against plant pathogens but also against human ones. A short analogue of EcgDf1 defensin, EcgDf21d (NH2‐ERFTGGHCRGFRRRCFCTKHC‐COOH), was labelled through the formation of a 99mTc‐HYNIC complex which was assessed for physicochemical and biological behaviour both in vitro and in vivo. The [99mTc]Tc‐HYNIC‐EcgDf21 labelling procedure rendered a single product with remarkably high RCP and stability in the labelling milieu. The Log p value indicated that [99mTc]Tc‐HYNIC‐EcgDf21 has a hydrophilic behaviour, confirmed by the biodistribution profiles. The optimal uptake value was obtained for Candida albicans infection model reaching a lesion/muscle ratio of 3, this correlates with in vitro binding studies, and the lesion can be definitely observed in the scintigraphic images. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases have mainly been associated with neuronal death. Recent investigations have shown that astroglia may modulate neuroinflammation in the early and late stages of the disease. [11C]Deuterodeprenyl ([11C]DED) is a tracer that has been used for reactive astrocyte detection in Alzheimer's disease, Creutzfeldt–Jakob disease and amyotrophic lateral sclerosis, among others, with some limitations. To develop a new radiotracer for detecting astrocytosis and overcoming associated difficulties, we recently reported the synthesis of a sulfonamide derivative of Sulforhodamine 101 (SR101), labeled with 18F, namely SR101 N -(3-[18F]Fluoropropyl) sulfonamide ([18F]2B-SRF101). The red fluorescent dye SR101 has been used as a specific marker of astroglia in the neocortex of rodents using in vivo models. In the present work we performed a biological characterisation of the new tracer including biodistribution and micro-PET/computed tomography (CT) images. PET/CT studies with [11C]DED were also done to compare with [18F]2B-SRF101 in order to assess its potential as an astrocyte marker. Biodistribution studies with [18F]2B-SRF101 were carried out in C57BL6J black and transgenic (3xTg) mice. A hepatointestinal metabolization as well as the pharmacokinetic profile were determined, showing appropriate characteristics to become a PET diagnostic agent. Dynamic PET/CT studies were carried out with [18F]2B-SRF101 and [11C]DED to evaluate the distribution of both tracers in the brain. A significant difference in [18F]2B-SRF101 uptake was especially observed in the cortex and hippocampus, and it was higher in 3xTg mice than it was in the control group. These results suggested that [18F]2B-SRF101 is a promising candidate for more extensive evaluation as an astrocyte tracer. The difference observed for [18F]2B-SRF101 was not found in the case of [11C]DED. The comparative studies between [18F]2B-SRF101 and [11C]DED suggest that both tracers have different roles as astrocytosis markers in this animal model, and could provide different and complementary information at the same time. In this way, by means of a multitracer approach, useful information could be obtained for the staging of the disease. [ABSTRACT FROM AUTHOR]

Background: Radiosynovectomy is a therapy used to relieve pain and inflammation from rheumatoid arthritis and related diseases. In this study three 188Re particulate compounds were characterized according to their physico-chemical properties and their biological behavior in rabbits. The results were compared in order to establish which was the radiopharmaceutical that better fits the requirements of this kind of radiotherapy. Methods: Three radiopharmaceutical formulations, tin colloid, hydroxyapatite particles (HA) and ferric hydroxide macroaggregates coated with tin colloid (FHMA), were physically characterized (number, volume and surface of the particles). For this purpose laser diffraction methodology was used. To evaluate cavity leakage of activity the following studies in New Zealand rabbits were performed: scintigraphic images for 48 hr after intraarticular injection of each radiopharmaceutical, biodistribution at 48 hr and urine samples collection during the first 24 hr post-radiopharmaceutical administration. Results: Labeling procedures for 188Re-HA and 188Re-Sn-FHMA were labour intensive while 188Re-Sn was easily prepared. Furthermore, 188Re-Sn colloid offered the greatest surface area in the 2-10 microm range and was obtained with a radiochemical purity over 95%, while percentage of bound activity for 188Re-HA and 188Re-Sn-FHMA were 55% and 92% respectively. Stability was verified for the three radiopharmaceuticals for 24 hr. Scintigraphic studies and biodistribution in rabbits after intraarticular administration of the radiopharmaceuticals showed relevant activity only in the knee, this being over 90% of the residual activity in the whole body at 48 hr in every case. Renal elimination of 188Re-Sn colloid and 188Re-Sn-FHMA was detected by activity measurements in urine samples, during the first 12 hr post-radiopharmaceutical injection. The percentage of activity retained in the knee was 69.1% for 188Re-Sn colloid, 55.1% for 188Re-Sn-FHMA and 33.6% for 188Re-HA. Conclusion: The 188Re-Sn colloid was easy to prepare, minimum facilities were required, was stable for 24 hr and showed minimal leakage from the joint after intraarticular injection into the rabbit's knee. Furthermore, 188Re-Sn colloid has greater retention in the knee when it is compared with the other radiopharmaceuticals, so it could provide the best therapeutic effect/ absorbed dose ratio for the patient. [ABSTRACT FROM AUTHOR]

Tablets containing drugs of different lipophilicity, ranitidine and cinarizine, and placebo were prepared and their in vitro behaviour was studied by dissolution and disintegration tests. [99mTc]Diethylenetriamine-pentaacetic acid (99mTc]DTPA) and [99mTc]ethyl cysteinate dimer ([99mTc]ECD) were used as tracers of the process. Both of them were added to tablets during wet granulation. Dissolution and disintegration profiles were assessed at different pH values (1, 4 and 7). Radioactivity was evaluated in filtered samples and scintigraphic studies were carried out in gamma camera. Stability in dissolution media was confirmed for both tracers under these conditions. Dissolution and disintegration velocity constants were calculated. [99mTc]DTPA proved to be an appropriate tracer for polar drugs such as ranitidine. Nevertheless, it was not a suitable tracer for lipophilic active drugs such as cinarizine. On the other hand, the most lipophilic tracer, [99mTc]ECD, exhibited the opposite behaviour. Scintigraphic studies of the disintegration process did not show significant differences between placebos and tablets containing active drugs. As disintegration is a physical process it does not discriminate between chemical differences in tablet formulations. Both methods complement each other because the dissolution process can be followed when a suitable radiotracer is chosen according to the physicochemical characteristics of the active drug. [Copyright &y& Elsevier]

Abstract: Introduction: There are many diseases associated with variations in the expression of apoptosis such as organ rejection after transplantation, myocardial ischemia or infarct and neurodegenerative diseases. For this reason, the early visualization of this process is relevant to set fast and effective therapeutic strategies. Methods: The precursor was prepared according to the procedure reported by R. Alberto, R. Schibli, P. Schubiger, U. Abram, and T. Kaden [Reactions with the technetium and rhenium carbonyl complexes (NEt4)[MX3(CO)3]. Synthesis and structure of Tc(CN-But)3(CO)3](NO3) and (Net4)[Tc2(μ-SCH2CH2OH)3(CO)3], Polyhedron 1996;15: 1079–89]. Recombinant annexin V was incubated with [99mTc](H2O)3(CO)3 + solution, previously neutralized with buffer. Biodistribution studies were performed in 8-week-old female Wistar rats. Animals were housed and treated in compliance with institutional guidelines related to animal experimentation. Work protocol was previously approved by the Animal Ethics Committee of the university. Two groups of rats were defined. One was used as control and the other group was previously injected with 150 mg/kg ip of cyclophosphamide to induce apoptosis. Results: The synthesis of carbonyl precursor achieved yields higher than 90%, and the radiolabeled protein was obtained with 92% of radiochemical purity and high stability in vitro. An important uptake in apoptotic tissues was confirmed by biodistributions, scintigraphic images and histological studies. Conclusions: Biodistribution studies revealed hepatobiliary elimination, high stability in vivo and important uptake in the reticuloendothelial system. In the pathologic model, higher uptake values correspond to the liver, spleen, lungs and femur. Histological studies confirmed the development of apoptosis at 8 and 24 h postinduction in the spleen and lymphocyte bulks in the peribronchial area. Scintigraphic images confirmed high uptake both the spleen and the lungs. [Copyright &y& Elsevier]

The development of new radiopharmaceuticals for the detection of hidden infection foci has great relevance for early detection and the selection of the correct treatment, particularly in immunosuppressed patients. In that sense, the labelling of antimicrobial peptides (AMPs) that are capable of binding specifically to the pathogenic microorganism which causes the infection, should provide a sufficiently specific agent, able to distinguish an infection from a sterile inflammation. Defensins are particularly interesting molecules with antimicrobial activity, the EcgDf1 defensin was identified from the genome of a Uruguayan native plant, Erythrina crista-galli, the 'Ceibo' tree. Our group has previously reported a synthetic biologically active short analogue EcgDf21 (ERFTGGHCRGFRRRCFCTKHC) successfully labelled with 99m Tc. Herein we present a shorter analogue which also preserves the γ-core domain, as a pharmacophore for a potential infection detection agent. This peptide was derivatized with the bifunctional chelating agent 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) through a lysine linker in the amino-terminal group (NOTA-KGHCRGFRRRC) and radiolabelled with 68 Ga ([ 68 Ga]Ga-NOTA-K-EcgDf1 (10) ). The [ 68 Ga]Ga-NOTA-K-EcgDf1 (10) labelling procedure rendered a product with high radiochemical purity and stability in the labelling milieu. The Log P value indicated that the complex has a hydrophilic behaviour, confirmed by the biodistribution profile. The [ 68 Ga]Ga-NOTA-K-EcgDf1 (10) complex demonstrated specific binding to cultures of Candida albicans and Aspergillus niger. Its biodistribution showed renal elimination and low accumulation in the rest of the body. It was possible to successfully differentiate sterile inflammation from infection by PET images in nude mice with a target/non-target ratio of 3.3 for C. albicans and 3.7 for A. niger, respectively., (© 2024 John Wiley & Sons Ltd.)

Background: Angiogenesis is a process that many tumors depend on for growth, development, and metastasis. Vascular endothelial growth factor (VEGF) is one of the major players in tumor angiogenesis in several tumor types, including melanoma. VEGF inhibition is achieved by bevacizumab, a humanized monoclonal antibody that binds with high affinity to VEGF and prevents its function. In order to successfully enable in vivo VEGF expression imaging in a murine melanoma model, we previously labeled bevacizumab with [ 99m Tc]Tc. We observed that this was feasible, but it had prolonged blood circulation and delayed tumor uptake., Objective: The aim of this study was to develop a radiolabeled Fab bevacizumab fragment, [ 99m Tc]Tc-HYNICFab( bevacizumab), for non-invasive in vivo VEGF expression molecular imaging., Methods: Flow cytometry was used to examine VEGF presence in the murine melanoma cell line (B16-F10). Bevacizumab was digested with papain for six hours at 37°C to produce Fab(bevacizumab), which was then conjugated to NHS-HYNIC-Tfa for radiolabeling with [ 99m Tc]Tc. Stability and binding affinity assays were also evaluated. Biodistribution and single photon emission computed tomography/computed tomography (SPECT/CT) were performed at 1, 3, and 6 h (n = 4) after injection of [ 99m Tc]Tc-HYNIC-Fab(Bevacizumab) in normal and B16-F10 tumor-bearing C57Bl/6J mice., Results: Using flow cytometry, it was shown that the B16-F10 murine melanoma cell line has intracellular VEGF expression. Papain incubation resulted in the complete digestion of bevacizumab with good purity and homogeneity. The radiolabeling yield of [ 99m Tc]Tc-HYNIC-Fab(bevacizumab) was 85.00 ± 6.06%, with a specific activity of 291.87 ± 18.84 MBq/mg (n=3), showing in vitro stability. Binding assays demonstrated significant intracellular in vitro VEGF expression. Fast blood clearance and high kidney and tumor uptake were observed in biodistribution and SPECT/CT studies., Conclusions: We present the development and evaluation of [ 99m Tc]Tc-HYNIC-Fab(bevacizumab), a novel molecular VEGF expression imaging agent that may be used for precision medicine in melanoma and potentially in other VEGF-expressing tumors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The role of monoamine oxidase A (MAO-A) in the aggressiveness of prostate cancer (PCa) has been established in recent years. The molecular imaging of MAO-A expression could offer a noninvasive tool for the visualization and quantification of highly aggressive PCa. This study reports the synthesis and preclinical evaluation of 11 C- and 18 F-labeled MAO-A inhibitors as positron emission tomography (PET) tracers for proof-of-concept studies in animal models of PCa. Good manufacturing practice production and quality control of these radiotracers using an automated platform was achieved. PET imaging was performed in an LNCaP tumor model with high MAO-A expression. The tumor-to-muscle (T/M) uptake ratio of [ 11 C]harmine (4.5 ± 0.5) was significantly higher than that for 2-[ 18 F]fluoroethyl-harmol (2.3 ± 0.7) and [ 11 C]clorgyline (2.0 ± 0.1). A comparable ex vivo biodistribution pattern in all radiotracers was observed. Furthermore, the tumor uptake of [ 11 C]harmine showed a dramatic reduction (T/M = 1) in a PC3 tumor model with limited MAO-A expression, and radioactivity uptake in LNCaP tumors was blocked in the presence of nonradioactive harmine. Our findings suggest that [ 11 C]harmine may serve as an attractive PET probe for the visualization of MAO-A expression in highly aggressive PCa. These radiotracers have the potential for clinical translation and may aid in the development of personalized therapeutic strategies for PCa patients., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Opportunistic infections are a problem of great relevance in public health and the precise detection and localization of infection in the early stages of the disease is of great importance for patient management as well as cost containment. Our proposal seeks to contribute to developing a new agent that meets the needs of diagnosis and follow-up of fungal and bacterial infections, focused on the design of a radiotracer with the potential for recognition of hidden infection foci. Defensins are plant antimicrobial peptides that not only show activity against plant pathogens but also against human ones. A short analogue of EcgDf1 defensin, EcgDf21d (NH 2 -ERFTGGHCRGFRRRCFCTKHC-COOH), was labelled through the formation of a 99m Tc-HYNIC complex which was assessed for physicochemical and biological behaviour both in vitro and in vivo. The [ 99m Tc]Tc-HYNIC-EcgDf21 labelling procedure rendered a single product with remarkably high RCP and stability in the labelling milieu. The Log p value indicated that [ 99m Tc]Tc-HYNIC-EcgDf21 has a hydrophilic behaviour, confirmed by the biodistribution profiles. The optimal uptake value was obtained for Candida albicans infection model reaching a lesion/muscle ratio of 3, this correlates with in vitro binding studies, and the lesion can be definitely observed in the scintigraphic images., (© 2022 John Wiley & Sons Ltd.)

Neurodegenerative diseases have mainly been associated with neuronal death. Recent investigations have shown that astroglia may modulate neuroinflammation in the early and late stages of the disease. [ 11 C]Deuterodeprenyl ([ 11 C]DED) is a tracer that has been used for reactive astrocyte detection in Alzheimer's disease, Creutzfeldt-Jakob disease and amyotrophic lateral sclerosis, among others, with some limitations. To develop a new radiotracer for detecting astrocytosis and overcoming associated difficulties, we recently reported the synthesis of a sulfonamide derivative of Sulforhodamine 101 (SR101), labeled with 18 F, namely SR101 N -(3-[ 18 F]Fluoropropyl) sulfonamide ([ 18 F]2B-SRF101). The red fluorescent dye SR101 has been used as a specific marker of astroglia in the neocortex of rodents using in vivo models. In the present work we performed a biological characterisation of the new tracer including biodistribution and micro-PET/computed tomography (CT) images. PET/CT studies with [ 11 C]DED were also done to compare with [ 18 F]2B-SRF101 in order to assess its potential as an astrocyte marker. Biodistribution studies with [ 18 F]2B-SRF101 were carried out in C57BL6J black and transgenic (3xTg) mice. A hepatointestinal metabolization as well as the pharmacokinetic profile were determined, showing appropriate characteristics to become a PET diagnostic agent. Dynamic PET/CT studies were carried out with [ 18 F]2B-SRF101 and [ 11 C]DED to evaluate the distribution of both tracers in the brain. A significant difference in [ 18 F]2B-SRF101 uptake was especially observed in the cortex and hippocampus, and it was higher in 3xTg mice than it was in the control group. These results suggested that [ 18 F]2B-SRF101 is a promising candidate for more extensive evaluation as an astrocyte tracer. The difference observed for [ 18 F]2B-SRF101 was not found in the case of [ 11 C]DED. The comparative studies between [ 18 F]2B-SRF101 and [ 11 C]DED suggest that both tracers have different roles as astrocytosis markers in this animal model, and could provide different and complementary information at the same time. In this way, by means of a multitracer approach, useful information could be obtained for the staging of the disease.