Photonic Lithotripsy: Near-Infrared Laser Activated Nanomaterials for Kidney Stone Comminution.

Near-infrared activated nanomaterials have been reported for biomedical applications ranging from photothermal tumor destruction to biofilm eradication and energy-gated drug delivery. However, the focus so far has been on soft tissues, and little is known about energy delivery to hard tissues, which have thousand-fold higher mechanical strength. We present photonic lithotripsy with carbon and gold nanomaterials for fragmenting human kidney stones. The efficacy of stone comminution is dependent on the size and photonic properties of the nanomaterials. Surface restructuring and decomposition of calcium oxalate to calcium carbonate support the contribution of photothermal energy to stone failure. Photonic lithotripsy has several advantages over current laser lithotripsy, including low operating power, noncontact laser operation (distances of at least 10 mm), and ability to break all common stones. Our observations can inspire the development of rapid, minimally invasive techniques for kidney stone treatment and extrapolate to other hard tissues such as enamel and bone.

Topical N-phosphonacetyl-l-aspartate is a dual action candidate for treating non-melanoma skin cancer.

Each year, 3.3 million Americans are diagnosed with non-melanoma skin cancers (NMSC) and an additional 40 million individuals undergo treatment of precancerous actinic keratosis lesions. The most effective treatments of NMSC (surgical excision and Mohs surgery) are invasive, expensive and require specialised training. More readily accessible topical therapies currently are 5-fluorouracil (a chemotherapeutic agent) and imiquimod (an immune modulator), but these can have significant side effects which limit their efficacy. Therefore, more effective and accessible treatments are needed for non-melanoma cancers and precancers. Our previous work demonstrated that the small molecule N-phosphonacetyl-L-aspartate (PALA) both inhibits pyrimidine nucleotide synthesis and activates pattern recognition receptor nucleotide-binding oligomerization domain 2. We propose that topical application of PALA would be an effective NMSC therapy, by combining the chemotherapeutic and immune modulatory features of 5-fluorouracil and imiquimod. Daily topical application of PALA to mouse skin was well tolerated and resulted in less irritation, fewer histopathological changes, and less inflammation than caused by either 5-fluorouracil or imiquimod. In an ultraviolet light-induced NMSC mouse model, topical PALA treatment substantially reduced the numbers, areas and grades of tumours, compared to vehicle controls. This anti-neoplastic activity was associated with increased expression of the antimicrobial peptide cathelicidin and increased recruitment of CD8+ T cells and F4/80+ macrophages to the tumours, demonstrating both immunomodulatory and anti-proliferative effects. These findings indicate that topical PALA is an excellent candidate as an effective alternative to current standard-of-care NMSC therapies.

Proof-of-concept for a novel nanotechnology-based treatment for urolithiasis.

Proof-of-concept of photonic lithotripsy in an in vitro setting and its ability to fragment the most common stone types is demonstrated. Effectiveness of different classes of photonic nanoparticles in fragmenting human stones is assessed. De-identified human stones were collected after institutional approval. Stones of a size range between 2-4 mm were rehydrated in simulated urine for 24 h. Stones were then coated with a solution of nanoparticles prior to activation with either a 785 nm or 1320 nm near-infrared energy source. Photonic lithotripsy achieved greater than 70% success rate in fragmentating calcium oxalate monohydrate stones using carbon-based nanoparticles for both near-infrared wavelengths. For gold-based nanoparticles, there was a similar success rate with the 785 nm wavelength but a significant decrease when using the 1320 nm wavelength energy source. All stones fragmented with the energy source at a distance ≥ 20 mm from the stone's surface. Limitations include the use of mixed-composition stones, a lack of complete stone immersion in liquid during treatment, and smaller stone size. Different classes of nanoparticles when excited with a near-infrared energy source can fragment common stone types in vitro. This technology has the potential to change the way we approach and treat patients with urolithiasis in a clinical setting.

Toward Accurate Calculation of Excitation Energies on Quantum Computers with ΔADAPT-VQE: A Case Study of BODIPY Derivatives.

Quantum chemistry simulations offer a cost-effective way to computationally design BODIPY photosensitizers. However, accurate predictions of excitation energies pose a challenge for time-dependent density functional theory and equation-of-motion coupled-cluster singles and doubles methods. By contrast, reliable predictions can be achieved by multireference quantum chemistry methods; unfortunately, their computational cost increases exponentially with the number of electrons. Alternatively, quantum computing holds potential for an exact simulation of the photophysical properties in a computationally more efficient way. Herein, we introduce the state-specific ΔUCCSD-VQE (unitary coupled-cluster singles and doubles-variational quantum eigensolver) and ΔADAPT-VQE methods in which the electronically excited state is calculated via a non-Aufbau configuration. We show for six BODIPY derivatives that the proposed methods predict accurate excitation energies that are in good agreement with those from experiments. Due to its performance and simplicity, we believe that ΔADAPT will become a useful approach for the simulation of BODIPY photosensitizers on near-term quantum devices.

Enzyme-independent catabolism of cysteine with pyridoxal-5'-phosphate.

Pyridoxal-5'-phosphate (PLP) is a versatile cofactor that assists in different types of enzymatic reactions. PLP has also been reported to react with substrates and catalyze some of these reactions independent of enzymes. One such catalytic reaction is the breakdown of cysteine to produce hydrogen sulfide (H2S) in the presence of multivalent metal ions. However, the enzyme-independent catalytic activity of PLP in catabolizing cysteine in the absence of multivalent ions is unknown. In this study, we show that PLP reacts with cysteine to form a thiazolidine product, which is supported by quantum chemical calculations of the absorption spectrum. The reaction of PLP with cysteine is dependent on ionic strength and pH. The thiazolidine product slowly decomposes to produce H2S and the PLP regenerates to its active form with longer reaction times (> 24 h), suggesting that PLP can act as a catalyst. We propose an enzyme-independent plausible reaction mechanism for PLP catalyzed cysteine breakdown to produce H2S, which proceeds through the formation of thiazolidine ring intermediates that later hydrolyzes slowly to regenerate the PLP. This work demonstrates that PLP catalyzes cysteine breakdown in the absence of enzymes, base, and multivalent metal ions to produce H2S.

Type C1 radical hysterectomy in advanced squamous cell carcinoma of the cervix postdefinitive concurrent chemoradiation: An argument.

Aims: This study aimed to evaluate the feasibility and outcomes of patients with advanced cervical cancer treated with definitive concurrent chemoradiotherapy followed by Type C 1 nerve-sparing radical hysterectomy. Settings and Design: This is a prospective study to assess the feasibility of Type C 1 nerve-sparing radical hysterectomy postdefinitive chemoradiation in advanced carcinoma cervix. Subjects and Methods: We analyzed 25 patients with cervical cancer evaluated and treated with concurrent chemoradiation followed by surgery. Twenty patients underwent Type C 1 nerve-sparing radical hysterectomy by open surgery and five patients by laparoscopic approach. Postoperative morbidity and pathology were analyzed. Statistical Analysis Used: Analysis of the outcomes was done by arithmetical calculations. Results: Eight patients (32%) had persistent residual disease after definitive chemoradiation followed by surgery. Rest of the patients had pathological complete response. Two patients (8%) had node-positive disease. None of the patients in the laparoscopic group had bladder morbidity. One patient in the laparoscopic group had persistent vaginal discharge. Conclusions: Type C1 nerve-sparing radical hysterectomy is technically feasible with minimal morbidity following definitive chemoradiation in advanced squamous cell carcinoma of the cervix.

Polyhydroxy Fullerenes Enhance Antibacterial and Electrocatalytic Activity of Silver Nanoparticles.

Silver nanoparticles (AgNPs) are known and widely used for their antibacterial properties. However, the ever-increasing resistance of microorganisms compels the design of novel nanomaterials which are able to surpass their capabilities. Herein, we synthesized silver nanoparticles using, for the first time, polyhydroxy fullerene (PHF) as a reducing and capping agent, through a one-pot synthesis method. The resulting nanoparticles (PHF-AgNPs) were compared to AgNPs that were synthesized using sodium citrate (citrate-AgNPs). They were characterized using high-resolution transmission electron microscopy (HR-TEM), dynamic light scattering, and UV-visible spectroscopy. Our results showed that PHF-AgNPs have a smaller size and a narrower size distribution than citrate-AgNPs, which suggests that PHF may be a better capping agent than citrate. Antibacterial assays using E. coli showed enhanced antimicrobial activity for PHF-AgNPs compared to citrate-AgNPs. The electrocatalytic activity of nanoparticles towards oxygen evolution and reduction reaction (OER and ORR, respectively) was tested through cyclic voltammetry. Both nanoparticles are found to promote OER and ORR, but PHF-AgNPs showed a significant increase in activity with respect to citrate-AgNPs. Thus, our results demonstrate that the properties of forming nanoparticles can be tuned by choosing the appropriate reducing/capping agent. Specifically, this suggests that PHF-AgNPs can find potential applications for both catalytic and biomedical applications.

The promise of nanotechnology for solving clinical problems in breast cancer.

Approaches for breast cancer treatment are invasive, disfiguring, have significant side-effects, and are not always curative. Nanotechnology is an emerging area which is focused on engineering of materials <100 × 10(-9) m. There is significant promise for advancing nanotechnology to improve breast cancer diagnosis and treatment including non-invasive therapy, monitoring response to therapy, advanced imaging, treatment of metastatic disease, and improved nodal staging. Current approaches and important future directions are discussed.

Copper coated silica nanoparticles for odor removal.

Copper species coated silica nanoparticles (CuOXS) were synthesized for odor removal application. Coating with copper increased the capacity of silica nanoparticles for eliminating a model odor-ethyl mercaptan. Surface area, pore size distribution, and electron paramagnetic resonance spectroscopy analyses indicated that, at lower copper concentrations, copper species preferentially adsorb in 20 Å pores of silica. These copper species in a dispersed state are effective in catalytic removal of ethyl mercaptan. The best performance of copper-coated silica nanoparticles was achieved at a copper concentration of 3 wt %, at which all 20 Å nanopores were filled with isolated copper species. At higher copper loading, copper species are present as clusters on silica surfaces, which were found to be less effective in removing ethyl mercaptan. Gas chromatography experiments were carried out to verify catalytic conversion of ethyl mercaptan to diethyl disulfide by CuOXS particles. The present study suggests that the nature of the copper species and their site of adsorption, as well as state of dispersion, are important parameters to be considered for catalytic removal of sulfur-containing compounds. These parameters are critical for designing high-performance catalytic copper-coated silica nanoparticles for applications such as deodorization, removal of sulfur compounds from crude oil, hydrogenation, and antimicrobial activity.

Photothermal Response of Polyhydroxy Fullerenes.

Photothermal therapy, utilizing photonic nanoparticles, has gained substantial interest as an alternative to systemic cancer treatments. Several different photothermal nanoparticles have been designed and characterized for their photothermal efficiency. However, a standardized experimental methodology to determine the photothermal efficiency is lacking leading to differences in the reported values for the same nanoparticles. Here, we have determined the role of different experimental parameters on the estimation of photothermal efficiency. Importantly, we have demonstrated the role of laser irradiation time and nanoparticle concentration as the two critical factors that can lead to errors in the estimation of photothermal efficiency. Based on the optimized parameters, we determined the photothermal conversion efficiency of polyhydroxy fullerenes to be 69%. Further, the photothermal response of polyhydroxy fullerenes was found to be stable with repeated laser irradiation and no changes in the molecular structure were observed. Given its high photothermal efficiency and superior stability, polyhydroxy fullerenes are an ideal candidate for photothermal therapy.

Effect of UVA irradiance on photocatalytic and UVA inactivation of Bacillus cereus spores.

The current study is the first to delineate the contribution of photocatalysis to inactivation of Bacillus cereus endospores on dry surfaces over a broad range (0-153W/m(2)) of UVA irradiance. Inactivation of spores at low UVA irradiance (30W/m(2)) was primarily due to photocatalysis, whereas at higher UVA irradiance inactivation was primarily due to UV alone. A linear relationship between UVA irradiance and the rate of spore inactivation was observed in the absence of photocatalyst. The rate of photocatalytic inactivation was non-linear with respect to UVA irradiance, exhibiting a maximum at 30W/m(2).

Toxicity of functionalized fullerene and fullerene synthesis chemicals.

Fullerene is one of the most studied carbon-based nanoparticles due to its unique structure and potential for diverse applications. This study focuses on toxicological effects of two fullerene nanomaterials, contributing to ecological as well as human risk assessment strategies. The biological responses from two basic fullerene materials, aqueous-nanoC60 and alkaline-synthesized fullerenol, were examined using four model organisms. Bioassays were conducted on bacteria (Pseudomonas aeruginosa and Staphylococcus aureus) to determine population impacts and to assess mechanisms of cellular effects for both Gram-negative and Gram-positive species. LC50 of aqu-nC60 stirred for 28 days for P. aeruginosa was estimated to be 1336 mg/L; however, toxicity of the same aqu-nC60 preparation for S. aureus was insignificant. Freshwater green algae Raphidocelus subcapitata and invertebrate Ceriodaphnia dubia were exposed to 28-day stirred aqu-nC60 with no significant toxicological impact. Aqu-nC60 stirred for 14 days bore no toxicity within two orders of magnitude greater than the highest concentration administered. LC50 for organisms exposed to alkaline-synthesized fullerenol prepared in the laboratory was 2409 mg/L for P. aeruginosa with no determinable toxicity to S. aureus, and 1462 mg/L and 45.2 mg/L for R. subcapitata and C. dubia, respectively. Toxicity thresholds for commercially-prepared fullerenol were lower for all species, an impact attributed to the presence of impurities. Mechanistic analysis of membrane damage on bacteria by laboratory-prepared fullerenol indicated necrotic and apoptotic responses with and without photoactivation. Toxicological responses from fullerenol synthesis by-products were only determinable for C. dubia with effects attributable to impurities.

Contaminant-Activated Visible Light Photocatalysis.

Pristine titanium dioxide (TiO2) absorbs ultraviolet light and reflects the entire visible spectrum. This optical response of TiO2 has found widespread application as white pigments in paper, paints, pharmaceuticals, foods and plastic industries; and as a UV absorber in cosmetics and photocatalysis. However, pristine TiO2 is considered to be inert under visible light for these applications. Here we show for the first time that a bacterial contaminant (Staphylococcus aureus-a MRSA surrogate) in contact with TiO2 activates its own photocatalytic degradation under visible light. The present study delineates the critical role of visible light absorption by contaminants and electronic interactions with anatase in photocatalytic degradation using two azo dyes (Mordant Orange and Procion Red) that are highly stable because of their aromaticity. An auxiliary light harvester, polyhydroxy fullerenes, was successfully used to accelerate photocatalytic degradation of contaminants. We designed a contaminant-activated, transparent, photocatalytic coating for common indoor surfaces and conducted a 12-month study that proved the efficacy of the coating in killing bacteria and holding bacterial concentrations generally below the benign threshold. Data collected in parallel with this study showed a substantial reduction in the incidence of infections.

Research strategies for safety evaluation of nanomaterials. Part VI. Characterization of nanoscale particles for toxicological evaluation.

To properly assign mechanisms or causes for toxic effects of nanoscale materials, their properties and characteristics both outside and within the biological environment must be well understood. Scientists have many tools for studying the size, shape, and surface properties of particulates outside of the physiological environment; however, it is difficult to measure many of these same properties in situ without perturbing the environment, leading to spurious findings. Characterizing nanoparticle systems in situ can be further complicated by an organism's active clearance, defense, and/or immune responses. As toxicologists begin to examine nanomaterials in a systematic fashion, there is consensus that a series of guidelines or recommended practices is necessary for basic characterization of nanomaterials. These recommended practices should be developed jointly by physical scientists skilled in nano characterization and biological scientists experienced in toxicology research. In this article, basic nanoparticle characterization techniques are discussed, along with the some of the issues and implications associated with measuring nanoparticle properties and their interactions with biological systems. Recommendations regarding how best to approach nanomaterial characterization include using proper sampling and measurement techniques, forming multidisciplinary teams, and making measurements as close to the biological action point as possible.

Enhancement of titanium dioxide photocatalysis by water-soluble fullerenes.

Fullerenes are known for their unique electronic properties including high electron affinity. Although use of fullerenes for scavenging photo-generated electrons from titanium dioxide particles has been demonstrated, no attempts have been made to utilize the unique properties of fullerenes to increase the efficacy of photocatalysis. The present study has demonstrated that a mixture of water-soluble polyhydroxy fullerenes (PHF) and titanium dioxide (anatase polymorph) enhances photocatalytic degradation of organic dye. The PHF molecules adsorbed to the surface of titanium dioxide due to electrostatic forces, with adsorption density being higher at lower pH values. The surface coverage of titanium dioxide nanoparticles by PHF molecules determined the extent of enhancement, with an optimum dosed weight ratio of PHF to titanium dioxide at 0.001. Hydroxylation and concomitant solubilization of fullerenes allow their unique electronic properties to be harnessed for photocatalysis.

Scombrotoxinism: Protracted Illness following Misdiagnosis in the Emergency Department.

Background. Scombrotoxinism is an acute toxin-induced illness caused primarily by bacterial synthesis of histamine in decomposed fish. Case Report. Immediately after taking 2-3 bites of cooked salmon, a clerical worker developed oral burning, urticaria, and asthma. In the emergency department, she was diagnosed with "allergies"; scombrotoxinism was never considered. She then developed wide-ranging symptoms (e.g., chronic fatigue, asthma, anxiety, multiple chemical sensitivity, and paresthesiae) and saw many specialists (in pulmonology, otorhinolaryngology, allergy, toxicology, neurology, psychology, and immunology). During the next 500+ days, she had extensive testing (allergy screens, brain MRI, electroencephalogram, electromyogram, nerve conduction velocity, heavy metal screen, and blood chemistry) with essentially normal results. She filed a workers' compensation claim since this injury occurred following a business meal. She was evaluated by a Qualified Medical Evaluator (GL) on day 504, who diagnosed scombrotoxinism. Comment. Scombrotoxinism should be considered in all patients presenting to the emergency department with "oral burning" or allergy symptoms following "fish consumption." Initial attention to such history would have led to a correct diagnosis and averted this patient's extended illness. Specialist referrals and tests should be ordered only if clinically indicated and not for diagnostic fishing expedition. Meticulous history is crucial in resolving clinical dilemmas.

Necrotizing fasciitis: diagnostic challenges in a mute bedridden patient with atypical laboratory parameters.

A 27-year-old mute bedridden patient required parenteral corticosteroids and antibiotics, and hospitalization for an acute respiratory illness. After 2 days, staff noted a ~0.3 cm blister on the patient's right heel. Within 19 hours, blistering increased and the foot became partly gangrenous. The patient developed high fever (40.3°C), and leukocytosis (count: 13 × 10(9)/L; was 6.5 × 10(9)/L ten days earlier). Necrotizing fasciitis (NF) was diagnosed and treated with emergency leg amputation. Histopathology revealed necrosis of fascia, muscle, subcutaneous tissue, and skin. In bedridden patients, corticosteroids may particularly facilitate serious infections, and initial NF blistering may be mistaken for pressure ulcers. Vigilant and frequent whole body monitoring is necessary for all patients incapable of verbalizing their symptoms.

Polyhydroxy fullerenes (fullerols or fullerenols): beneficial effects on growth and lifespan in diverse biological models.

Recent toxicological studies on carbon nanomaterials, including fullerenes, have led to concerns about their safety. Functionalized fullerenes, such as polyhydroxy fullerenes (PHF, fullerols, or fullerenols), have attracted particular attention due to their water solubility and toxicity. Here, we report surprisingly beneficial and/or specific effects of PHF on model organisms representing four kingdoms, including the green algae Pseudokirchneriella subcapitata, the plant Arabidopsis thaliana, the fungus Aspergillus niger, and the invertebrate Ceriodaphnia dubia. The results showed that PHF had no acute or chronic negative effects on the freshwater organisms. Conversely, PHF could surprisingly increase the algal culture density over controls at higher concentrations (i.e., 72% increase by 1 and 5 mg/L of PHF) and extend the lifespan and stimulate the reproduction of Daphnia (e.g. about 38% by 20 mg/L of PHF). We also show that at certain PHF concentrations fungal growth can be enhanced and Arabidopsis thaliana seedlings exhibit longer hypocotyls, while other complex physiological processes remain unaffected. These findings may open new research fields in the potential applications of PHF, e.g., in biofuel production and aquaculture. These results will form the basis of further research into the mechanisms of growth stimulation and life extension by PHF.

Optical heating and rapid transformation of functionalized fullerenes.

Irradiating single-walled carbon nanotubes can lead to heat generation or ignition. These processes could be used in medical and industrial applications, but the poor solvent compatibility and high aspect ratios of nanotubes have led to concerns about safety. Here, we show that certain functionalized fullerenes, including polyhydroxy fullerenes (which are known to be environmentally safe and to have therapeutic properties) are heated or ignited by exposure to low-intensity (<10(2 ) W cm(-2)) continuous-wave laser irradiation. We also show that polyhydroxy fullerenes and other functionalized fullerenes can be transformed into single-walled nanotubes, multiwalled nanotubes and carbon onions without the presence of a catalyst by exposure to low-intensity laser irradiation in an oxygen-free environment. To demonstrate the potential usefulness of these processes in applications, we disrupted animal cells dosed with polyhydroxy fullerenes by exposing them to a near-infrared laser for a few seconds, and also ignited an explosive charge in contact with a particle of carboxy fullerenes.