Conventional photodynamic therapy (PDT) is limited by the penetration depth of visible light needed for its activation. Here we used mesoporous-silica-coated upconversion fluorescent nanoparticles (UCNs) as a nanotransducer to convert deeply penetrating near-infrared light to visible wavelengths and a carrier of photosensitizers. We also used the multicolor-emission capability of the UCNs at a single excitation wavelength for simultaneous activation of two photosensitizers for enhanced PDT. We showed a greater PDT efficacy with the dual-photosensitizer approach compared to approaches using a single photosensitizer, as determined by enhanced generation of singlet oxygen and reduced cell viability. In vivo studies also showed tumor growth inhibition in PDT-treated mice by direct injection of UCNs into melanoma tumors or intravenous injection of UCNs conjugated with a tumor-targeting agent into tumor-bearing mice. As the first demonstration, to the best of our knowledge, of the photosensitizer-loaded UCN as an in vivo-targeted PDT agent, this finding may serve as a platform for future noninvasive deep-cancer therapy.

Near-infrared (NIR)-to-visible up-conversion fluorescent nanoparticles have potential to be used for photodynamic therapy (PDT) in deep tissue because NIR light can penetrate thick tissue due to weak absorption in the optical window. Here a uniform layer of mesoporous silica is coated onto NaYF(4) up-converting nanocrystals, with a large surface area of approximately 770 m(2) g(-1) and an average pore size of 2 nm. A photosensitizer, zinc phthalocyanine, is incorporated into the mesoporous silica. Upon excitation by a NIR laser, the nanocrystals convert NIR light to visible light, which further activates the photosensitizer to release reactive singlet oxygen to kill cancer cells. The photosensitizer encapsulated in mesoporous silica is protected from degradation in the harsh biological environment. It is demonstrated that the photosensitizers loaded into the porous silica shell of the nanoparticles are not released out of the silica while they continuously produce singlet oxygen upon excitation by a NIR laser. The nanoparticles are reusable as the photosensitizers encapsulated in the silica are removed by soaking in ethanol.

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The Headache Classification Committee of the International Headache Society listed impairments in cervical muscle function as criteria for headaches of cervical spine origin. Fifteen subjects with cervical headache and 15 controls were tested for the frequency of abnormal responses to passive stretching and abnormal muscle contraction. A new test of cranio-cervical flexion was used to assess the contraction of the deep neck flexors. Results indicated a trend towards a higher frequency of abnormal response to passive stretching of the muscles examined in the cervical headache group but only the upper trapezius proved significantly different to the control group. Deep neck flexor muscle contraction was significantly inferior in the cervical headache group. From the perspective of physical characterization of cervical headache, it appears that response from passive stretch of muscle may not be a strong criterion for cervical headache but deep neck flexor performance may have potential to identify musculoskeletal involvement in headache. The finding may also provide positive directions for conservative treatment of cervical headache.

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Cystoscopy is considered the gold standard for the clinical diagnosis of human bladder cancer (BC). As cystoscopy is expensive and invasive, it may compromise patients' compliance and account for the failure in detecting recurrent BC in some patients. In this paper, we investigated the role of urinary metabonomics in the diagnosis of human BC. Gas chromatography/time-of-flight mass spectrometry was applied for the urinary metabolic profiling of 24 BC patients and 51 non-BC controls. The acquired data were analyzed using multivariate principal component analysis followed by orthogonal partial least-squares discriminant analysis (OPLS-DA). Model validity was verified using permutation tests and receiver operating characteristic (ROC) analysis. BC patients were clearly distinguished from non-BC subjects based on their global urinary metabolic profiles (OPLS-DA, 4 latent variables, R(2)X = 0.420, R(2)Y = 0.912 and Q(2) (cumulative) = 0.245; ROC AUC of 0.90; 15 marker metabolites). One-hundred percent sensitivity in detecting BC was observed using urinary metabonomics versus 33% sensitivity achieved by urinary cytology. Additionally, urinary metabonomics exhibited potential in the staging and grading of bladder tumors. In summary, urinary metabonomics is amenable for the noninvasive diagnosis of human BC.

However, most attempts to detect in vitro-in vivo correlations were unsuccessful, emphasizing the challenges of anti-TB drug discovery. The objective of this work is to provide a reference dataset for the TB drug discovery community with a focus on comparative in vitro potency and pharmacokinetics.