Photo-responsive functional gold nanocapsules for inactivation of community-acquired, highly virulent, multidrug-resistant MRSA.

The indiscriminate and sporadic use of antibiotics has contributed to the emergence of drug resistance phenomenon in bacteria including but not limited to Staphylococcus aureus. These drug-resistant bacteria have been threatening safety in hospitals and adversely affecting human health. Here we report a strategy to design photo-stimulated theranostic nanoprobes against methicillin-resistant Staphylococcus aureus (MRSA) "superbug" USA300. The nanocapsule probe is based on gold nanorods (GNRs) coated with pegylated thiol, mPEG-SH, which has been further modified by adding successively a natural antibacterial compound such as curcumin, and a cell targeting deoxyribonucleic acid (DNA) aptamer. We have used this novel gold nanocapsules for near-infrared (NIR) photophysical stimulation against pathogenic bacteria. We have found that the novel nanocapsule blocks biofilm formation and kills bacteria by photothermal action that causes disruption of the bacterial cell wall and membrane. In this approach, multiple drug-resistant Staphylococcus aureus has been captured by these nanocapsules through DNA aptamer targeting. All of the trapped bacteria could be killed in 30 minutes during the NIR stimulation due to the combination of photothermal effect, the generation of reactive oxygen species (ROS) and a loss of transmembrane potential (Δψ). Importantly we did not notice any resistance developed against the photothermal treatment. This is remarkable from an anti-biofilm activity point of view. Importantly, these multifunctional nanocapsules have also shown a surface enhanced Raman spectroscopy (SERS) effect, which could be used to evaluate the success of the inactivation effect during treatment. These results indicate that nanocapsule-based photo treatment can be an alternative antibacterial strategy without contributing to antibiotic resistance, and thus can be used for both environmental and therapeutic applications.

Nanomedicine-driven molecular targeting, drug delivery, and therapeutic approaches to cancer chemoresistance.

Cancer cell resistance to chemotherapeutics (chemoresistance) poses a significant clinical challenge that oncology research seeks to understand and overcome. Multiple anticancer drugs and targeting agents can be incorporated in nanomedicines, in addition to different treatment modalities, forming a single nanoplatform that can be used to address tumor chemoresistance. Nanomedicine-driven molecular assemblies using nucleic acids, small interfering (si)RNAs, miRNAs, and aptamers in combination with stimuli-responsive therapy improve the pharmacokinetic (PK) profile of the drugs and enhance their accumulation in tumors and, thus, therapeutic outcomes. In this review, we highlight nanomedicine-driven molecular targeting and therapy combination used to improve the 3Rs (right place, right time, and right dose) for chemoresistant tumor therapies.

Polarisation changes in guided infrared thermography using silver halide poly-crystalline mid-infrared fibre bundle.

Broadband mid-infrared (B-MIR) thermography using fibre optic waveguides can be critical in real-time imaging in harsh environments such as additive manufacturing, personalised medical diagnosis and therapy. We investigate the polarisation effect on thermal measurements through poly-crystalline fibre bundle employing a simple broadband cross-polarisation configuration experimental set-up. Silver halide poly-crystalline fibres AgCl1-xBrx (0 ≤ x≤1) (AgClBr-PolyC) have very wide transmission bandwidth spanning over the spectral range from 1 µm up to 31 µm FWHM. Moreover, they are non-toxic, non-hygroscopic, with relatively good flexibility, which make them very adequate for spectroscopic and thermal measurements in medical and clinical fields. In this study, we used a fibre bundle composed of seven single AgClBr-PolyC fibres, each with a core diameter of about 300 µm, inserted between two broadband MIR polarisers. A silicon carbide filament source was placed at the entrance of the fibre bundle, while a FLIR thermal camera with a close-up lens was employed to measure the spatial temperature distribution over the fibre-bundle end. Indeed, polarisation dependence of temperature measurements has been clearly observed in which the orientation of temperature extrema (minima and maxima) vary from one fibre to another within the bundle. Moreover, these observations have enabled the classification of AgClBr-PolyC fibres following their polarisation sensitivities by which some fibres are relatively highly sensitive to polarisation with polarisation temperature difference (PTD) that can reach 22.1 ± 2.8 °C, whereas some others show very low PTD values down to 3.1 ± 2.8 °C. Many applications can readily be found based on the advantages of both extreme cases.

Spectral drifts in surface textured Fe3O4-Au, core-shell nanoparticles enhance spectra-selective photothermal heating and scatter imaging.

We report a significant spectral drift (up to 110 nm) between optical scattering and extinction in magnetite-gold (Fe3O4-Au) core-shell nanostructures. The drift was observed experimentally using single-particle broadband dark-field scattering microspectroscopy and solution extinction experiments. Infrared thermography demonstrates an enhanced photothermal activity of these nanoparticles at extinction wavelengths that are far drifted from the wavelengths that produce the best results for imaging via scattering. For example, a relatively smooth gold shell leads to 19% more photothermal activity at 532 nm compared to 690 nm whereas a rough-texture, popcorn type morphology gold shell with three times higher drift, is 170% more efficient at 532 nm. We suggest that the enhanced photothermal response results directly from a reduced competition between absorption and scattering as a consequence of the spectral drift. This spectral drift can be advantageous in multimodal theranostics where therapy and imaging are performed independently at different wavelengths.

Surface Texturing Design to Enhance Echogenicity of Biopsy Needles During Endoscopic Ultrasound Imaging.

The ultrasonic visibility of a biopsy needle tip is of critical importance for the success and safety of endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) procedures. The aim of this study was to design a surface topology, in silico, which enhances the ultrasound visibility of a needle by controlling and optimising the direction of the reflections. Topographic enhancements to needle surface redirect scattered waves back to the transducer to enhance needle visibility, or "echogenicity." Echogenicity enhancement is demonstrated across insonification angles of 30°-90° on full-length scale of biopsy needles used in practice. By applying a textured surface across the full length of the needle surface, the signal being returned to the transducer can be tripled from that of a constant periodic dimple echogenic surface and seven times that of an untextured flat surface. Our first principles model provides a quantitative insight to echogenicity and its enhancement. The model allows in silico design of needles for USG-FNA and biopsy with enhanced echogenicity and consequent improvement in visibility, including but not limited to needle tip area.

Comprehensive approach of hybrid nanoplatforms in drug delivery and theranostics to combat cancer.

To date, various chemically synthesized and biosynthesized nanoparticles, or hybrid nanosystems and/or nanoplatforms, have been developed under the umbrella of nanomedicine. These can be introduced into the body orally, nasally, intratumorally or intravenously. Successfully translating hybrid nanoplatforms from preclinical proof-of-concept to therapeutic value in the clinic is challenging. Having made significant advances with drug delivery technologies, we must learn from other areas of oncology drug development, where patient stratification and target-driven design have improved patient outcomes. This review aims to identify gaps in our understanding of the current strengths of nanomedicine platforms in drug delivery and cancer theranostics. We report on the current approaches of nanomedicine at preclinical and clinical stages.

Implementation of artificial intelligence and non-contact infrared thermography for prediction and personalized automatic identification of different stages of cellulite.

BACKGROUND: Cellulite is a common physiological condition of dermis, epidermis, and subcutaneous tissues experienced by 85 to 98% of the post-pubertal females in developed countries. Infrared (IR) thermography combined with artificial intelligence (AI)-based automated image processing can detect both early and advanced cellulite stages and open up the possibility of reliable diagnosis. Although the cellulite lesions may have various levels of severity, the quality of life of every woman, both in the physical and emotional sphere, is always an individual concern and therefore requires patient-oriented approach. OBJECTIVES: The purpose of this work was to elaborate an objective, fast, and cost-effective method for automatic identification of different stages of cellulite based on IR imaging that may be used for prescreening and personalization of the therapy. MATERIALS AND METHODS: In this study, we use custom-developed image preprocessing algorithms to automatically select cellulite regions and combine a total of 9 feature extraction methods with 9 different classification algorithms to determine the efficacy of cellulite stage recognition based on thermographic images taken from 212 female volunteers aged between 19 and 22. RESULTS: A combination of histogram of oriented gradients (HOG) and artificial neural network (ANN) enables determination of all stages of cellulite with an average accuracy higher than 80%. For primary stages of cellulite, the average accuracy achieved was more than 90%. CONCLUSIONS: The implementation of computer-aided, automatic identification of cellulite severity using infrared imaging is feasible for reliable diagnosis. Such a combination can be used for early diagnosis, as well as monitoring of cellulite progress or therapeutic outcomes in an objective way. IR thermography coupled to AI sets the vision towards their use as an effective tool for complex assessment of cellulite pathogenesis and stratification, which are critical in the implementation of IR thermographic imaging in predictive, preventive, and personalized medicine (PPPM).

MRI Guided Magneto-chemotherapy with High-Magnetic-Moment Iron Oxide Nanoparticles for Cancer Theranostics.

Elevating and monitoring the temperature of tumors using magnetic nanoparticles (MNPs) still presents a challenge in magnetic hyperthermia therapy. The efficient heating of tumor volume can be achieved by preparing MNPs with high magnetization values. The next-generation approach to magnetic resonance image (MRI)-guided magneto-chemotherapy of cancer based on high-magnetic-moment iron oxide nanoparticles is proposed. The proof of concept is validated by cellular MRI experiments on breast cancer cells. To explore magneto-chemotherapy, we developed high-magnetic-moment iron oxide (Fe3O4) nanoparticles (NPs) using base diisopropylamine (DIPA), which plays a dual role as reducing agent and surface stabilizer. Spherical NPs with ∼12 nm size and a high magnetization value of about 92 emu g-1 at room temperature are obtained by this unique method. A high specific absorption rate value of ∼717 wg-1 was obtained for Fe3O4 NPs in water at an alternating magnetic field of 20 kAm-1 and frequency of 267 kHz, which is attributed to the high magnetization value. The magneto-polymeric micelle structure is formed by using Pluronic F127, and anticancer drug doxorubicin is conjugated in the micelle by electrostatic interactions for magneto-chemotherapy. Finally, the magnetic resonance imaging (MRI)-guided magneto-chemotherapy was achieved on breast cancer (MCF7) cells with an overall ∼96% killing of cancer cells attained in 30 min of magneto-chmeotherapy.

Silica nano supra-assembly for the targeted delivery of therapeutic cargo to overcome chemoresistance in cancer.

Cancer cells become resistant over the period to chemotherapeutic drugs and pose a challenging impediment for oncologists in providing effective treatment. Nanomedicine allows to overcome chemoresistance and is the focus of our investigation. Silica nanostructures have been highlighted as an interesting drug delivery platform in vitro and in vivo applications. Here we show the validity of nanomedicine approach for targeted chemotherapeutic cargo delivery to overcome chemoresistance in cancer cells both in vitro and in vivo. For demonstrating the concept, we functionalised ∼100 nm long porous silica nanoparticles (∼20 nm diameter ordered pore structure) by conjugating anticancer drug, cytochrome c enzyme and dual-function anticancer aptamer AS1411 in single supra-assembled nanocargos. The supra-assembly on the porous silica nanostructure allows for a high loading of catalytic enzyme cytochrome c, anticancer drug and aptamer. The silica supra-assembly is characterized by transmission electron microscopy (TEM) and Brunauer-Emmett-Teller (BET) surface area analysis. Conjugation of cargoes has been monitored at each step by UV-vis and Fluorescence spectroscopy. Finally, the constructed supra-assembled nanocarrier tested on chemoresistance colon cancer (HCT116) cells. A pH-responsive, intracellular theranostic cargo delivery has been achieved and the triple action of the nanocargo made an efficient killing of drug resistance colon cancer cells in vitro (∼ 92% cell death) through triplex therapy effects by supressing the P-glycoprotein (P-gp) level. Furthermore, in vivo animal toxicity studies demonstrated, the supra-assembled nanocargos have encouraging safety index to be used in cancer therapy and drug delivery applications.

Thermal effects of mobile phones on human auricle region.

Mobile phones have become an indispensable utility to modern society, with international use increasing dramatically each year. The GSM signal operates at 900 MHz, 1800 MHz and 2250 MHz, may potentially cause harm to human tissue. Yet there is no in silico model to aid design these devices to protect from causing potential thermal effect. Here we present a model of sources of heating in a mobile phone device with experimental verification during the phone call. We have developed this mobile phone thermal model using first principles on COMSOL® Multiphysics modelling platform to simulate heating effect in human auricle region due to mobile phone use. In particular, our model considered both radiative and non-radiative heating from components such as the lithium ion battery, CPU circuitry and the antenna. The model showed the distribution and effect of the heating effect due to mobile phone use and considered impact of battery discharge rate, battery capacity, battery cathode material, biological tissue distance, antenna radio-wave frequency and intensity. Furthermore, the lithium ion battery heating was validated during experiments using temperature sensors with an excellent agreement between simulated and experimental data (<1% variation). Mobile phone heating during a typical call has also been simulated and compared with experimental infrared thermographic imaging. Importantly, we found that 1800 MHz frequency of data transmission showed the highest temperature increase in the fat/water phantom used in this simulation. We also successfully compared heating distribution in human auricle region during mobile phone use with clinical thermographic images with reasonable qualitative and quantitative agreements. In summary, our model provides a foundation to conceive thermal and other physical effects caused by mobile phone use and allow for the understanding of potential negative health effects thus supporting and promoting personalized and preventive medicine using thermography.

Progress in Remotely Triggered Hybrid Nanostructures for Next-Generation Brain Cancer Theranostics.

Progress in nanomedicine has enabled the development of smart hybrid nanostructures (HNSs) for brain cancer theranostics, a novel platform that can diagnose the brain while concurrently beginning primary treatment, initiating secondary treatments where necessary, and monitoring the therapy response. These HNSs can release guest molecules/cargoes directly to brain tumors in response to external physical stimuli. Such physical stimulation is generally referred to as remote stimuli which can be externally applied examples include alternating magnetic field, visible or near-infrared light, ultrasound radiation, X-ray, and radiofrequency. The release of therapeutic cargoes in response to physical stimuli can be performed along with photodynamic therapy, photothermal therapy, phototriggered chemotherapeutics, sonodynamic therapy, electrothermal therapy, and magnetothermal therapy. Herein, we review different HNSs currently used as remotely triggered modalities in brain cancer, such as organic-inorganic HNSs, polymer micelles, and liposomes HNSs. We also summarize underlying mechanisms of remote triggering brain cancer therapeutics including single- and two-photon triggering, thermoresponsive HNSs, photoresponsive HNSs, magnetoresponsive HNSs, and electrically and ultrasound-stimulated HNSs. In addition to a brief synopsis of ongoing research progress on "smart" HNSs-based platforms of novel brain cancer therapeutics, the review offers an up-to-date development in this field for neuro-oncologists, material/nanoscientists, and radiologists so that a rapid clinical impact can be achieved through a convergence of multidisciplinary expertise.

Electrically Polarized Biomaterials.

Electrically polarized biomaterials and their interactions with the surrounding biological environment is important for understanding the host response, growth and inhibition of biological species as well as the long-term fate and performance of the implants. Polarized materials possess electrical charges at the surface due to polar or electret properties. As these surfaces are at the frontier of biological reactions understanding biological interactions at the interface with polarized biomaterials requires a convergence of understanding multiple disciplines. This article discusses progress that has taken place in the fields of surface and interface science, materials science and biomedical device engineering to obtain a better perspective of such interactions.

Leaving before discharge from a homeless Medical Respite program: predisposing factors and impact on selected outcomes.

BACKGROUND: Medical Respite addresses care needs of homeless patients post-hospital discharge and is linked to reduced rehospitalization compared with standard discharge. However, outcomes may differ for Respite patients who exit before completing post-acute treatment and discharge plans. METHODS: Using administrative data from a San Francisco Medical Respite center (2007-2010), this retrospective study compares patient characteristics, post-Respite connections to community services, and likelihood of rehospitalization within 90 days of Respite exit between patients who choose to leave before discharge and all other Respite patients (logistic regression, odds ratio). FINDINGS: Of 860 encounters, 31% ended when patient chose to leave before discharge. Female gender (OR 1.65), living on the street immediately prior to Respite (OR 1.36) and substance use (OR 1.55) were associated with increased risk of leaving early. Patients who left early were more likely than others to decline referrals to services and more likely to be re-admitted within 90 days.

The impact of citizenship documentation requirements on access to medicaid for pregnant women in Oregon.

The federal Deficit Reduction Act of 2005 mandated citizenship documentation from all Medicaid applicants as a condition of eligibility and was implemented in Oregon on September 1, 2006. We assessed whether new citizenship documentation requirements were associated with delays in Medicaid authorization for newly pregnant eligible applicants during the first nine months of DRA implementation in Oregon. We conducted a pre-post analysis of administrative records to compare the length of time between Medicaid application and authorization for all newly pregnant, Medicaid-eligible applicants in Oregon (n = 29,284), nine months before and after September 1, 2006. We compared mean days from application to authorization (McNemar's), and proportion of eligible applicants who waited over 7, 30 and 45 days to be authorized (Pearson's coefficient). The mean number of days women waited for authorization increased from 18 days in the 9 months before DRA implementation to 22.6 days in the post-implementation 9 month period (P ≤ .001). The proportion of eligible applicants who waited 7, 30 and 45 days increased significantly following DRA implementation (P ≤ .001). The proportion of eligible applicants who were not authorized within the standard 45-day period increased from 6.9 to 12.5% following the DRA. Implementation of new citizenship documentation requirements was associated with significant delays in Medicaid authorization for eligible pregnant women in Oregon. Such delays in gaining insurance coverage can detrimentally affect access to early prenatal care initiation among a vulnerable population known to be at higher risk for certain preventable pregnancy-related complications.

Overdose prevention and naloxone prescription for opioid users in San Francisco.

Opiate overdose is a significant cause of mortality among injection drug users (IDUs) in the United States (US). Opiate overdose can be reversed by administering naloxone, an opiate antagonist. Among IDUs, prevalence of witnessing overdose events is high, and the provision of take-home naloxone to IDUs can be an important intervention to reduce the number of overdose fatalities. The Drug Overdose Prevention and Education (DOPE) Project was the first naloxone prescription program (NPP) established in partnership with a county health department (San Francisco Department of Public Health), and is one of the longest running NPPs in the USA. From September 2003 to December 2009, 1,942 individuals were trained and prescribed naloxone through the DOPE Project, of whom 24% returned to receive a naloxone refill, and 11% reported using naloxone during an overdose event. Of 399 overdose events where naloxone was used, participants reported that 89% were reversed. In addition, 83% of participants who reported overdose reversal attributed the reversal to their administration of naloxone, and fewer than 1% reported serious adverse effects. Findings from the DOPE Project add to a growing body of research that suggests that IDUs at high risk of witnessing overdose events are willing to be trained on overdose response strategies and use take-home naloxone during overdose events to prevent deaths.

Silica sol-gel matrix doped with Photolon molecules for sensing and medical therapy purposes.

Photolon is one of the new photosensitisers that has found application in photodynamic therapy (PDT). Its chemical structure has a partially reduced porphyrin moiety and its molecular structure is comparable to chlorin e(6), which can be isolated after hydrolysis of the 5-membered exocyclic beta-ketoester moiety of pheophorbide a. For this study, a Photolon doped sol-gel matrix was produced in the form of coatings deposited on silica fibers cores. The material was produced from sols prepared from the silicate precursor TEOS mixed with ethyl alcohol. The sol-gel films were prepared with factor R=20, where R denotes the solvent-to-precursor molar ratio. Hydrochloric acid was added as a catalyst in the correct proportion to ensure acid hydrolysis (pH approximately 2). The mixture was stirred at room temperature for 4h using a magnetic stirrer (speed 400 rpm). The coated fibers were examined in different environments, liquid and gaseous, at different pH values and with various zinc cation concentrations. The chemical reactions were studied by means of spectroscopic methods, whereby the fluorescence response was studied. It was demonstrated that Photolon immobilized in a sol-gel matrix is accessible for the environment and shows visible response to the external changes. Furthermore, it was observed that these reactions are reversible. These biomaterials are also examined as carriers for PDT. It was also proved that a toxic effect is observed an environment with microorganisms, meaning that doped coatings have photodynamic activity.

[Assessment of the possibilities of application of the thermovision technique in medico-legal diagnosis. Theoretical basis]. / Ocena mozliwosci zastosowania techniki termowizyjnej w diagnostyce medyczno-sadowej. Podstawy teoretyczne.

The authors in their work wish to prove that technological advancement of modern thermovision technique opens for forensic medicine, as an applied science, new diagnostic possibilities, especially in the scope of the post-mortem examinations. In the past, some attempts were already undertaken to apply thermovision techniques in forensic medicine, those tests, however, were not put in the everyday medical-legal practice. Most of the factors which have an influence in decreasing the value of thermograph tests are not present while biological material is tested post-mortem, therefore, paradoxically, natural elimination of obstacles occurs in such cases, which allows for medical-legal post-mortem diagnostics based on thermograph images. In particular, the most promising is active dynamic thermography which is based on the analysis of thermograms' sequence registered during transitional thermal processes in the examined object (heating or cooling of the object), which is stimulated by an external heat source, and the object's response to this stimulation is a change of the temperature which function in time determines its internal structure. Pathological and injury changes and their results in the form of structural damages of tissues lead to thermal conductivity and capacity which can be noticeable in a thermovision test. There are, then, no theoretical obstacles to the use of active dynamic thermography in post-mortem tests of tissues to evaluate their structure. With today's technological progress, it should be expected that in the near future sensitivity of thermovision appliances will significantly influence the increase of the specificity of obtained images. It can not be excluded that thermography methods could become a back-up method or even an alternative for other imagining methods.