Biosynthesis of polyhydroxybutyrate from methane and carbon dioxide using type II methanotrophs.

Methane (CH4) and carbon dioxide (CO2) are the dominant greenhouse gases (GHGs) that are increasing at an alarming rate. Methanotrophs have emerged as potential CH4 and CO2 biorefineries. This study demonstrated the synchronous incorporation of CH4 and CO2 into polyhydroxybutyrate (PHB) for the first time using 13C-labeling experiments in methanotrophs. By supplying substantial amounts of CO2, PHB content was enhanced in all investigated type II methanotrophic strains by 140 %, 146 %, and 162 %. The highest content of PHB from CH4 and CO2 in flask-scale cultivation reached 38 % dry cell weight in Methylocystis sp. MJC1, in which carbon percentage in PHB from CO2 was 45 %. Flux balance analysis predicted the critical roles of crotonyl-CoA carboxylase/reductase and phosphoenolpyruvate carboxylase in CO2 recycling. This study provided proof of the conversion of GHGs into a valuable and practical product using methanotrophic bacteria, contributing to addressing GHG emissions.

Supervised Pelvic Floor Muscle Training Improves Sexual Function and Diminishes Sexual Distress in Women with Relapsing-Remitting Multiple Sclerosis: A Randomised Controlled Study.

This study investigates the impact of pelvic floor muscle training (PFMT) on sexual function and distress in women with multiple sclerosis (MS), a prevalent chronic nervous system disorder associated with sexual dysfunction. This study's primary aim was to assess the effectiveness of PFMT at improving sexual function and alleviating sexual distress in this population. In a randomised controlled trial, 82 women with MS were divided into two groups: Group A (41 women) underwent 12 weeks of PFMT, while Group B (41 women) served as a control group with no intervention. Both groups were assessed at the beginning and end of this study using the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R). Statistical analysis, including Chi-square tests, was employed to compare the outcomes between the two groups, with a p-value of less than 0.05 considered significant. The results revealed no significant differences in baseline sexual function and distress between the groups. However, at the conclusion of the 12-week period, Group A exhibited statistically significant improvements in nearly all domains of FSFI and FSDS-R compared to Group B, except in the pain domain. This study concludes that PFMT can effectively enhance sexual function and reduce sexual distress in women suffering from MS. These findings underscore the potential of PFMT as a therapeutic intervention in managing sexual dysfunction associated with MS.

Management of Male Infertility with Coexisting Sexual Dysfunction: A Consensus Statement and Clinical Recommendations from the Asia-Pacific Society of Sexual Medicine (APSSM) and the Asian Society of Men's Health and Aging (ASMHA).

Male infertility (MI) and male sexual dysfunction (MSD) can often coexist together due to various interplay factors such as psychosexual, sociocultural and relationship dynamics. The presence of each form of MSD can adversely impact male reproduction and treatment strategies will need to be individualized based on patients' factors, local expertise, and geographical socioeconomic status. The Asia Pacific Society of Sexual Medicine (APSSM) and the Asian Society of Men's Health and Aging (ASMHA) aim to provide a consensus statement and practical set of clinical recommendations based on current evidence to guide clinicians in the management of MI and MSD within the Asia-Pacific (AP) region. A comprehensive, narrative review of the literature was performed to identify the various forms of MSD and their association with MI. MEDLINE and EMBASE databases were searched for the following English language articles under the following terms: "low libido", "erectile dysfunction", "ejaculatory dysfunction", "premature ejaculation", "retrograde ejaculation", "delayed ejaculation", "anejaculation", and "orgasmic dysfunction" between January 2001 to June 2022 with emphasis on published guidelines endorsed by various organizations. This APSSM consensus committee panel evaluated and provided evidence-based recommendations on MI and clinically relevant MSD areas using a modified Delphi method by the panel and specific emphasis on locoregional socio-economic-cultural issues relevant to the AP region. While variations exist in treatment strategies for managing MI and MSD due to geographical expertise, locoregional resources, and sociocultural factors, the panel agreed that comprehensive fertility evaluation with a multidisciplinary management approach to each MSD domain is recommended. It is important to address individual MI issues with an emphasis on improving spermatogenesis and facilitating reproductive avenues while at the same time, managing various MSD conditions with evidence-based treatments. All therapeutic options should be discussed and implemented based on the patient's individual needs, beliefs and preferences while incorporating locoregional expertise and available resources.

Development of Activity Rules and Chemical Fragment Design for In Silico Discovery of AChE and BACE1 Dual Inhibitors against Alzheimer's Disease.

Multi-target drug development has become an attractive strategy in the discovery of drugs to treat of Alzheimer's disease (AzD). In this study, for the first time, a rule-based machine learning (ML) approach with classification trees (CT) was applied for the rational design of novel dual-target acetylcholinesterase (AChE) and ß-site amyloid-protein precursor cleaving enzyme 1 (BACE1) inhibitors. Updated data from 3524 compounds with AChE and BACE1 measurements were curated from the ChEMBL database. The best global accuracies of training/external validation for AChE and BACE1 were 0.85/0.80 and 0.83/0.81, respectively. The rules were then applied to screen dual inhibitors from the original databases. Based on the best rules obtained from each classification tree, a set of potential AChE and BACE1 inhibitors were identified, and active fragments were extracted using Murcko-type decomposition analysis. More than 250 novel inhibitors were designed in silico based on active fragments and predicted AChE and BACE1 inhibitory activity using consensus QSAR models and docking validations. The rule-based and ML approach applied in this study may be useful for the in silico design and screening of new AChE and BACE1 dual inhibitors against AzD.

Novel (E)-3-(3-Oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides as Histone Deacetylase Inhibitors: Design, Synthesis and Bioevaluation.

Herein, we report the design, synthesis and evaluation of novel (E)-3-(3-oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides (4 a-i, 7 a-g) targeting histone deacetylases. Three human cancer cell lines were used to test the cytotoxicity of the synthesized compounds (SW620, colon; PC-3, prostate; NCI-H23, lung cancer); inhibitory activity towards HDAC; anticancer activity; as well as their impact on the cell cycle and apoptosis. As a result, compounds 4 a-i bearing the alkyl substituents seemed to be less potent than the benzyl-containing compounds 7 a-g in all biological assays. Compounds 7 e-f were found to be the most active HDAC inhibitors with IC50 of 1.498±0.020 µM and 1.794±0.159 µM, respectively. In terms of cytotoxicity and anticancer assay, 7 e and 7 f also showed good activity with IC50 values in the micromolar range. In addition, the cell cycle and apoptosis of SW620 were affected by compound 7 f in almost a similar manner to that of reference compound SAHA. Docking assays were carried out for analysis the binding mode and selectivity of this compound toward 8 HDAC isoforms. Overall, our data confirmed that the inhibition of HDAC plays a pivotal role in their anticancer activity.

Clinical recommendations on penile reconstructive and prosthetic surgery: a consensus statement from the Asia-Pacific Society of Sexual Medicine.

Introduction: Penile reconstructive and prosthetic surgery remains a highly specialized field where potential complications can be devastating, and unrealistic patient expectations can often be difficult to manage. Furthermore, surgical practice can vary depending on locoregional expertise and sociocultural factors. Methods: The Asia Pacific Society of Sexual Medicine (APSSM) panel of experts reviewed contemporary evidence regarding penile reconstructive and prosthetic surgery with an emphasis on key issues relevant to the Asia-Pacific (AP) region and developed a consensus statement and set of clinical practice recommendations on behalf of the APSSM. The Medline and EMBASE databases were searched using the following terms: "penile prosthesis implant," "Peyronie's disease," "penile lengthening," "penile augmentation," "penile enlargement," "buried penis," "penile disorders," "penile trauma," "transgender," and "penile reconstruction" between January 2001 and June 2022. A modified Delphi method was undertaken, and the panel evaluated, agreed, and provided consensus statements on clinically relevant penile reconstructive and prosthetic surgery, namely (1) penile prosthesis implantation, (2) Peyronie's disease, (3) penile trauma, (4) gender-affirming (phalloplasty) surgery, and (5) penile esthetic (length and/or girth enlargement) surgery. Main outcome measures: Outcomes were specific statements and clinical recommendations according to the Oxford Centre for Evidence-Based Medicine, and if clinical evidence is lacking, a consensus agreement is adopted. The panel provided statements on clinical aspects of surgical management in penile reconstructive and prosthetic surgery. Results: There is a variation in surgical algorithms in patients based on sociocultural characteristics and the availability of local resources. Performing preoperative counseling and obtaining adequate informed consent are paramount and should be conducted to discuss various treatment options, including the pros and cons of each surgical intervention. Patients should be provided with information regarding potential complications related to surgery, and strict adherence to safe surgical principles, preoperative optimization of medical comorbidities and stringent postoperative care are important to improve patient satisfaction rates. For complex patients, surgical intervention should ideally be referred and performed by expert high-volume surgeons to maximize clinical outcomes. Clinical implications: Due to the uneven distribution of surgical access and expertise across the AP region, development of relevant comprehensive surgical protocols and regular training programs is desirable. Strengths and Limitations: This consensus statement covers comprehensive penile reconstructive and prosthetic surgery topics and is endorsed by the APSSM. The variations in surgical algorithms and lack of sufficient high-level evidence in these areas could be stated as a limitation. Conclusion: This APSSM consensus statement provides clinical recommendations on the surgical management of various penile reconstructive and prosthetic surgeries. The APSSM advocates for surgeons in AP to individualize surgical options based on patient condition(s) and needs, surgeon expertise, and local resources.

Methanotrophs as a reservoir for bioactive secondary metabolites: Pitfalls, insights and promises.

Methanotrophs are potent natural producers of several bioactive secondary metabolites (SMs) including isoprenoids, polymers, peptides, and vitamins. Cryptic biosynthetic gene clusters identified from these microbes via genome mining hinted at the vast and hidden SM biosynthetic potential of these microbes. Central carbon metabolism in methanotrophs offers rare pathway intermediate pools that could be further diversified using advanced synthetic biology tools to produce valuable SMs; for example, plant polyketides, rare carotenoids, and fatty acid-derived SMs. Recent advances in pathway reconstruction and production of isoprenoids, squalene, ectoine, polyhydroxyalkanoate copolymer, cadaverine, indigo, and shinorine serve as proof-of-concept. This review provides theoretical guidance for developing methanotrophs as microbial chassis for high-value SMs. We summarize the distinct secondary metabolic potentials of type I and type II methanotrophs, with specific attention to products relevant to biomedical applications. This review also includes native and non-native SMs from methanotrophs, their therapeutic potential, strategies to induce silent biosynthetic gene clusters, and challenges.

TSSNote-CyaPromBERT: Development of an integrated platform for highly accurate promoter prediction and visualization of Synechococcus sp. and Synechocystis sp. through a state-of-the-art natural language processing model BERT.

Since the introduction of the first transformer model with a unique self-attention mechanism, natural language processing (NLP) models have attained state-of-the-art (SOTA) performance on various tasks. As DNA is the blueprint of life, it can be viewed as an unusual language, with its characteristic lexicon and grammar. Therefore, NLP models may provide insights into the meaning of the sequential structure of DNA. In the current study, we employed and compared the performance of popular SOTA NLP models (i.e., XLNET, BERT, and a variant DNABERT trained on the human genome) to predict and analyze the promoters in freshwater cyanobacterium Synechocystis sp. PCC 6803 and the fastest growing cyanobacterium Synechococcus elongatus sp. UTEX 2973. These freshwater cyanobacteria are promising hosts for phototrophically producing value-added compounds from CO2. Through a custom pipeline, promoters and non-promoters from Synechococcus elongatus sp. UTEX 2973 were used to train the model. The trained model achieved an AUROC score of 0.97 and F1 score of 0.92. During cross-validation with promoters from Synechocystis sp. PCC 6803, the model achieved an AUROC score of 0.96 and F1 score of 0.91. To increase accessibility, we developed an integrated platform (TSSNote-CyaPromBERT) to facilitate large dataset extraction, model training, and promoter prediction from public dRNA-seq datasets. Furthermore, various visualization tools have been incorporated to address the "black box" issue of deep learning and feature analysis. The learning transfer ability of large language models may help identify and analyze promoter regions for newly isolated strains with similar lineages.

Comparison of the University Pharmacy Education Programs in Germany and Vietnam.

During the global COVID pandemic, the importance of professionals in the health care sector has been put in a new light, including pharmacists. In this context, the focus is also on how pharmacists are trained in different countries. Through an exchange of pharmacy teaching staff from a German to a Vietnamese university, the pharmacy education programs in both countries were compared. Aspects such as access to studies, structure of studies, and further training opportunities were considered. Differences and similarities emerged. In both countries, students first acquire basic knowledge and then delve deeper into pharmaceutical content in main studies. There is, expectedly, a great overlap in the content of the courses. Overall, the education at Vietnamese universities seems to be more practice-oriented due to a large number of placements. This also allows a specialization, which can be pursued in Germany with self-interest after graduation. There, the preparation for everyday work in the community pharmacy is separated from the university by a mandatory practical year. For the future, efforts are being made in both countries to strengthen the importance of clinical pharmacy in the curriculum. To this end, the Vietnamese are taking their inspiration from abroad in many cases, including Germany.

Reconstructing ethanol oxidation pathway in Pseudomonas putida KT2440 for bio-upgrading of ethanol to biodegradable polyhydroxybutanoates.

Ethanol has recently been demonstrated as a suitable carbon source for acetyl-CoA-derived products with high theoretical yield. Herein, the short-chain-length polyhydroxyalkanoates production pathway was constructed in an industrial platform P. putida KT2440, allowing the engineered strain to produce 674.97 ± 22.3 mg/L of Polyhydroxybutyrate (PHB) from ethanol as sole carbon source. Furthermore, the ethanol catabolic pathway was reconstructed to enhance the acetyl-coA pool by expressing the novel Aldehyde dehydrogenases from Klebsiella pneumonia and Dickeya zeae, resulting in a titer of 1385.34 ± 16.5 mg/L and 9300 ± 0.56 mg/L of PHB in shake flask and fermenter, respectively. Furthermore, transcriptome analysis was conducted to provide insights into the central metabolic pathways and different expression patterns in response to changes in substrate. Additionally, the production of co-polymer poly(3-hydroxybutyrate-co-3-hydroxypropionate) was shown using glycerol and ethanol as co-substrates from recombinant P. putida KT2440. This work demonstrates the potential of P. putida KT2440 as a promising industrial platform for short-chain-length PHAs production from structurally unrelated carbon sources.

Development of Methylorubrum extorquens AM1 as a promising platform strain for enhanced violacein production from co-utilization of methanol and acetate.

Violacein, a blue-violet compound with a wide range of beneficial bioactivities, is an attractive product for microbial production. Currently, violacein production has been demonstrated in several sugar heterotrophs through metabolic engineering; however, the cost of production remains an obstacle for business ventures. To address this issue, the development of host strains that can utilize inexpensive alternative substrates to reduce production costs would enable the commercialization of violacein. In this study, we engineered a facultative methylotroph, Methylorubrum extorquens AM1, to develop a methanol-based platform for violacein production. By optimizing expression vectors as well as inducer concentrations, 11.7 mg/L violacein production was first demonstrated using methanol as the sole substrate. Considering that unidentified bottlenecks for violacein biosynthesis in the shikimate pathway of M. extorquens AM1 would be difficult to address using generic metabolic engineering approaches, random mutagenesis and site-directed mutagenesis were implemented, and a 2-fold improvement in violacein production was achieved. Finally, by co-utilization of methanol and acetate, a remarkable enhancement of violacein production to 118 mg/L was achieved. Our results establish a platform strain for violacein production from non-sugar feedstocks, which may contribute to the development of an economically efficient large-scale fermentation system for violacein production.

Removal of beta-lactam antibiotic in water environment by adsorption technique using cationic surfactant functionalized nanosilica rice husk.

This study aims to investigate the adsorption characteristics of cationic surfactant, cetyltrimethylamonium bromide (CTAB) onto negatively nanosilica rice husk surface and the application for antibiotic treatment in water environment. Adsorption of CTAB onto nanosilica increased with an increase of solution pH, due to an enhancement of the electrostatic attraction between cationic methylamomethylamonium groups and negatively charged nanosilica surface enhanced at higher pH. Adsorption of CTAB decreased with a decrease of ionic strength while a common intersection point (CIP) was observed for adsorption isotherm at different ionic strengths, suggesting that hydrophobic interactions between alkyl chains in CTAB molecules significantly induced adsorption and admicelles with bilayer formation were dominant than monolayer of hemimicelles. The CTAB functionalized nanosilica (CFNS) was applied for removal of beta-lactam amoxicillin (AMX). The best conditions for AMX treatment using CFNS were selected as pH 10, contact time 60 min and CFNS dosage 10 mg/mL. Removal efficiency of AMX using CFNS reached to 100% under optimum conditions while it was only 25.01% using nanosilica without CTAB. The maximum AMX adsorption capacity using CFNS of about 25 mg/g was much higher than other adsorbents. The effects of different organics such as humic acid, anionic surfactant, and other antibiotics on AMX removal using CFNS were also studied. A two-step model can fit CTAB uptake isotherms onto nanosilica and AMX onto CFNS well at different KCl concentrations. Based on the desorption of CTAB with AMX adsorption as well as adsorption isotherms, the change in surface charge and functional vibration groups after adsorption, we indicate that AMX adsorption onto CFNS was mainly controlled by electrostatic interaction. We reveal that CFNS is an excellent adsorbent for antibiotic treatment from aqueous solution.

Adsorptive Removal of Anionic Azo Dye New Coccine Using Silica and Silica-gel with Surface Modification by Polycation.

In the present work, adsorption of anionic azo dye, new coccine (NCC) on silica and silica-gel in an aquatic environment was discovered. Effective conditions such as adsorption time, pH, the influence of dosage on NCC adsorption using strong polycation, poly-diallyl-dimethylammonium chloride (PDADMAC) modified silica (PMS) and PDADMAC modified silica-gel (PMSG) were systematically studied. The removal of NCC using PMS and PMSG were much higher than that using raw silica and silica-gel without PDADMAC in all pH ranges from 3 to 10. The adsorption of NCC onto PMS and PMSG was achieved maxima at the same conditions of contact time 30 min, pH 6. The optimum adsorbent dosages of PMS and PMSG for NCC removal were 10 and 20 mg·mL-1, respectively. Experimental results of NCC adsorption isotherms onto PMS and PMSG at different ionic strength were fitted by Langmuir and Freundlich models. The NCC removal efficiencies using PMS and PMSG were higher than 87%, indicating that PMS and PMSG are novel and reusable adsorbents for removal of anionic dye. Based on adsorption isotherms, and surface group changes after PDADMAC modification and NCC adsorption examined by Fourier transform infrared spectroscopy (FTIR), we demonstrate that electrostatic interaction between positively charged adsorbents' surfaces and negative sulfonic groups of NCC are the main driving force for anionic azo dye adsorption onto PMS and PMGS adsorbents.

COVID Pandemic Impact on Healthcare Provision and Patient Psychosocial Distress: A Multi-National Cross-Sectional Survey among Asia-Pacific Countries.

PURPOSE: COVID pandemic significantly affected the delivery and maintenance of healthcare system, resulting in greater utilization of digital health interventions. MATERIALS AND METHODS: This multi-national cross-sectional survey was administered to clinicians working in major Asia-Pacific cities during the mandatory social lockdown period in June 2020. Clinical demographics and professional data, delivery of Andrology-related healthcare services, and patient distress based on validated questionnaires such as Depression and Anxiety Stress Scales (DASS) and Decisional Engagement Scale (DES) were collected. RESULTS: Telehealth medicine was instituted in all the centres with the majority of centres (92.9%) reported a 50% or more reduction in out-patient related services. The numbers of phone calls, emails correspondence and educational webinars have significantly increased. Despite the provision of reasons for changes in healthcare service and delay in surgery, more than half of the patients (57.1%) rated 2 on the DASS score for the item on patients over-react to situations, while a third of the patients (35.7%) scored a 2 for DASS item on patients being more demanding or unreasonable. The DES scores were more positive with most patients reported a score above 7 out of 10 in terms of items on accepting current arrangement (85.7%), confident in clinician decision-making about treatment (92.9%) and comfortable that the decision is consistent with their preferences (71.4%). Most patients (85.7%) indicated their preferences for more detailed information on healthcare provision. CONCLUSIONS: Our study showed telehealth services were integrated early and successfully during the COVID pandemic and patients were generally receptive with minimal psychosocial distress.

Rapid Lipid Modification of Endothelial Cell Membranes in Cardiac Ischemia/Reperfusion Injury: a Novel Therapeutic Strategy to Reduce Infarct Size.

PURPOSE: Plasma membranes constitute a gathering point for lipids and signaling proteins. Lipids are known to regulate the location and activity of signaling proteins under physiological and pathophysiological conditions. Membrane lipid therapies (MLTs) that gradually modify lipid content of plasma membranes have been developed to treat chronic disease; however, no MLTs have been developed to treat acute conditions such as reperfusion injury following myocardial infarction (MI) and percutaneous coronary intervention (PCI). A fusogenic nanoliposome (FNL) that rapidly incorporates exogenous unsaturated lipids into endothelial cell (EC) membranes was developed to attenuate reperfusion-induced protein signaling. We hypothesized that administration of intracoronary (IC) FNL-MLT interferes with EC membrane protein signaling, leading to reduced microvascular dysfunction and infarct size (IS). METHODS: Using a myocardial ischemia/reperfusion swine model, the efficacy of FNL-MLT in reducing IS following a 60-min coronary artery occlusion was tested. Animals were randomized to receive IC Ringer's lactate solution with or without 10 mg/mL/min of FNLs for 10 min prior to reperfusion (n = 6 per group). RESULTS: The IC FNL-MLT reduced IS (25.45 ± 16.4% vs. 49.7 ± 14.1%, P < 0.02) and enhanced regional myocardial blood flow (RMBF) in the ischemic zone at 15 min of reperfusion (2.13 ± 1.48 mL/min/g vs. 0.70 ± 0.43 mL/min/g, P < 0.001). The total cumulative plasma levels of the cardiac injury biomarker cardiac troponin I (cTnI) were trending downward but were not significant (999.3 ± 38.7 ng/mL vs. 1456.5 ± 64.8 ng/mL, P = 0.1867). However, plasma levels of heart-specific fatty acid binding protein (hFABP), another injury biomarker, were reduced at 2 h of reperfusion (70.3 ± 38.0 ng/mL vs. 137.3 ± 58.2 ng/mL, P = 0.0115).  CONCLUSION: The IC FNL-MLT reduced IS compared to vehicle in this swine model. The FNL-MLT maybe a promising adjuvant to PCI in the treatment of acute MI.

Provision of Sexual Medicine Services During the Coronavirus Disease-2019 Pandemic: An Asia Pacific Society of Sexual Medicine Position Statement.

The coronavirus disease-2019 (COVID-19) pandemic has caused an unprecedented healthcare crisis with various governmental healthcare policies enforced to redirect medical prioritization and minimize the spread of COVID19 infection. Recognizing that the COVID-19 crisis will be protracted, it is important that clinicians and the healthcare industry continue to adapt existing resources and review contingency plan amidst this uncertain and difficult times. The Asia Pacific Society of Sexual Medicine supports ongoing precautionary healthcare measures implemented by various institutions and governmental policies to contain and eliminate COVID19 infection. Clinicians are encouraged to modify and adapt various strategies that will continue to provide, support, and treat sexual health-related conditions in a safe and efficient manner. Chung E, Jiann BP, Nagao L, et al. Provision of Sexual Medicine Services During the Coronavirus Disease-2019 Pandemic: An Asia Pacific Society of Sexual Medicine Position Statement. J Sex Med 2020;8:325-326.

Developments of Riboswitches and Toehold Switches for Molecular Detection-Biosensing and Molecular Diagnostics.

Riboswitches and toehold switches are considered to have potential for implementation in various fields, i.e., biosensing, metabolic engineering, and molecular diagnostics. The specific binding, programmability, and manipulability of these RNA-based molecules enable their intensive deployments in molecular detection as biosensors for regulating gene expressions, tracking metabolites, or detecting RNA sequences of pathogenic microorganisms. In this review, we will focus on the development of riboswitches and toehold switches in biosensing and molecular diagnostics. This review introduces the operating principles and the notable design features of riboswitches as well as toehold switches. Moreover, we will describe the advances and future directions of riboswitches and toehold switches in biosensing and molecular diagnostics.

Gold Nanoparticle-Based Fluorescent Contrast Agent with Enhanced Sensitivity.

Gold nanoparticle (GNP) based contrast agents that are highly specific and sensitive for both optical and X-ray/CT imaging modalities are being developed for detecting the cancer expressing nucleolin and matrix metallo-proteinase 14 (MMP-14) on the cell membrane: Nucleolin is normally present in the nucleus. For many cancer cells, however, it is over-expressed on the cell membrane, having it to be a good cancer marker. Aptamer AS1411 is known to be an excellent target for nucleolin and also known to treat several cancer types; and MMP-14 in cancer is involved in tumor angiogenesis, blood vessel re-organization, and metastasis. In the proposed agent, AS1411 is selected as the cancer targeting molecule; and the unique property of GNPs of modulating fluorescence are utilized to allow the agent to trigger its fluorescence upon reacting with MMP-14, at an enhanced fluorescence level. GNPs are also natural X-ray/CT contrast agent. Here, as a part of on-going development of the dual-modality contrast agent, we report that conjugating a safe, NIR fluorophore Cypate at a precisely determined distance from the GNP enhanced the Cypate fluorescence up to two times. In addition, successful conjugation of the nucleolin target AS1411 onto the GNP was confirmed and among the GNPs size range 5-30 nm tested, 10 nm GNPs showed the highest X-ray/CT enhancement.

Exploring Design Opportunities for a Context-Adaptive Medical Checklist Through Technology Probe Approach.

This paper explores the workflow and use of an interactive medical checklist for trauma resuscitation-an emerging technology developed for trauma team leaders to support decision making and task coordination among team members. We used a technology probe approach and ethnographic methods, including video review, interviews, and content analysis of checklist logs, to examine how team leaders use the checklist probe during live resuscitations. We found that team leaders of various experience levels use the technology differently. Some leaders frequently glance at the checklist and take notes during task performance, while others place the checklist on a stand and only interact with the checklist when checking items. We compared checklist timestamps to task activities and found that most items are checked off after tasks are performed. We conclude by discussing design implications and new design opportunities for a future dynamic, adaptive checklist.

MMP-14 Triggered Fluorescence Contrast Agent.

Matrix metalloproteinase-14 (MMP-14) is involved in cancer invasion, metastasis, and angiogenesis. Therefore, it is considered to be a biomarker for aggressive cancer types, including some of the triple-negative breast cancer. Accurate (i.e., specific) and sensitive detection of MMP-14 can, thus, be important for the early diagnosis of and accurate prognosis for aggressive cancer, including the breast cancer caused by cell line MDA-MB 231. Fluorophore-mediated molecular sensing has been used for detecting biomarkers, for a long time. One way to increase the specificity of the sensing is designing the fluorophore to emit its fluorescence only when it encounters the biomarker of interest. When a fluorophore is placed on the surface of, or very close to a gold nanoparticle (GNP), its fluorescence is quenched. Applying this relationship between the GNP and fluorophore, we have developed a GNP-based, near-infrared fluorescent contrast agent that is highly specific for MMP-14. This agent normally emits only 14-17 % fluorescence of the free fluorophore. When the agent encounters MMP-14, its fluorescence gets fully restored, allowing MMP-14 specific optical signal emission.