Overcoming barriers in photodynamic therapy harnessing nano-formulation strategies.

Photodynamic therapy (PDT) has been extensively investigated for decades for tumor treatment because of its non-invasiveness, spatiotemporal selectivity, lower side-effects, and immune activation ability. It can be a promising treatment modality in several medical fields, including oncology, immunology, urology, dermatology, ophthalmology, cardiology, pneumology, and dentistry. Nevertheless, the clinical application of PDT is largely restricted by the drawbacks of traditional photosensitizers, limited tissue penetrability of light, inefficient induction of tumor cell death, tumor resistance to the therapy, and the severe pain induced by the therapy. Recently, various photosensitizer formulations and therapy strategies have been developed to overcome these barriers. Significantly, the introduction of nanomaterials in PDT, as carriers or photosensitizers, may overcome the drawbacks of traditional photosensitizers. Based on this, nanocomposites excited by various light sources are applied in the PDT of deep-seated tumors. Modulation of cell death pathways with co-delivered reagents promotes PDT induced tumor cell death. Relief of tumor resistance to PDT with combined therapy strategies further promotes tumor inhibition. Also, the optimization of photosensitizer formulations and therapy procedures reduces pain in PDT. Here, a systematic summary of recent advances in the fabrication of photosensitizers and the design of therapy strategies to overcome barriers in PDT is presented. Several aspects important for the clinical application of PDT in cancer treatment are also discussed.

Multifunctional Nanodroplets Encapsulating Naphthalocyanine and Perfluorohexane for Bimodal Image-Guided Therapy.

Although nanocarriers containing perfluorocarbon (PFC) have been widely investigated as an ultrasound (US) imaging agent and a high intensity focused ultrasound (HIFU) agent, these carriers have suffered from low stability and biocompatibility limiting their further biomedical applications. Here, we developed surface cross-linked polymer nanodroplets as a HIFU therapeutic agent guided by bimodal photoacoustic (PA) and US imaging. Pluronic F127 was reacted with 4-nitrophenyl chloroformate (NPC) and mixed with naphthalocyanine (Nc) in dichloromethane, which was added into the aqueous solution of amine-functionalized six-arm-branched poly(ethylene glycol) (PEG) to form an oil-in-water emulsion for the cross-linking reaction between the terminal NPC of Pluronic F127 and the primary amine of six-arm PEG. The resulting solution was sonicated with liquid perfluorohexane (PFH) to prepare PEG cross-linked Pluronic F127 nanoparticles encapsulating Nc and PFH (Nc/PFH@PCPN). Nc/PFH@PCPN appeared to be stable without any coalescence or vaporization in the physiological condition. Upon the application of HIFU, Nc/PFH@PCPN was vaporized and showed increased US intensity for 180 min. The Nc dye in the nanodroplets enabled the stable encapsulation of PFH and the bimodal US/PA imaging. In vivo PA/US image-guided HIFU ablation therapy confirmed that the nanodroplets increased the cavitation effect, induced necrosis and apoptosis of tumor cells, and reduced tumor growth significantly for 12 days. Taken together, the multifunctional Nc/PFH@PCPN was successfully developed as a new platform for PA/US image-guided HIFU therapy.

Correlation of occupational stress with depression, anxiety, and sleep in Korean dentists: cross-sectional study.

BACKGROUND: This study aimed to investigate the degree of occupational stress and the clinical mental state of dentists. In addition, we investigated the correlation of occupational stress with depression, anxiety, and sleep among dentists in Korea. METHODS: A cross-sectional survey on 231 dentists was conducted using the Doctor Job Stress Scale, Center for Epidemiologic Studies Depression Scale (CES-D), State-Trait Anxiety Index (STAI), and Pittsburgh Sleep Quality Index (PSQI). Correlation of occupational stress with mental health was investigated by adjusted multiple regression analysis. RESULTS: The scores of CES-D, STAI, and PSQI revealed a significant correlation with the Doctor Job Stress Scale (t = 3.93, P < 0.0001; t = 4.05, P < 0.0001; t = 4.18, P < 0.0001, respectively). In particular, patient factors and clinical responsibility/judgment factors were significantly associated with depression (t = 2.80, P = 0.0056; t = 4.93, P < 0.0001, respectively), anxiety (t = 2.35, P = 0.0195; t = 5.11, P < 0.0001, respectively), and sleep (t = 3.78, P = 0.0002; t = 4.30, P < 0.0001, respectively), whereas work factors were not associated with any mental health state. CONCLUSIONS: This study confirms that dentists as professions experience more severe mental states. For successful mental health care among dentists, stress management focusing on interpersonal relationship with patients and responsibility as an expert rather than the intensity of work should be considered.

Immunohistochemical localization and distribution of proliferating cell nuclear antigen in the rabbit mandibular condyle following experimental induction of anterior disk displacement.

The purpose of the present study was to identify proliferating cells in control versus experimental condyles two weeks following experimental induction of anterior disk displacement (ADD) in the rabbit craniomandibular joint (CMJ). The right joint of 15 rabbits was exposed surgically and all diskal attachments were severed except for the posterior attachment. The disk was then repositioned anteriorly and sutured to the zygomatic arch. The left joint served as a sham-operated control. Ten additional joints were used as nonoperated controls. Mandibular condyles were excised two weeks following surgery and processed for proliferating cell nuclear antigen (PCNA) immunostaining. In control and sham operated condyles, PCNA was localized in the nuclei of chondroblasts of the reserve cell layer, chondrocytes of the upper hypertrophic layer and bone marrow cells of the subchondral bone. In contrast to control joints, the PCNA positive cells of the experimental joints were located throughout the osteoarthritic condylar cartilage. In addition, the percentage of PCNA positive cells of the osteoarthritic condylar cartilage was statistically significantly higher when compared to the control group, p < 0.05. It was concluded that surgical induction of ADD in the rabbit CMJ leads to an increase in mitosis of chondrocytes, which lead to cell proliferation and subsequent hyperplasia of the condylar cartilage.

Mild copper-TBAF-catalyzed N-arylation of sulfoximines with aryl siloxanes.

An efficient copper-TBAF-catalyzed C-N bond formation of sulfoximines with arylsiloxanes in dichloromethane at room temperature, affording the desired N-aryl sulfoximines in good to excellent yields under an oxygen atmosphere, is reported. This method complements the existing synthetic approaches due to some advantageous properties of arylsiloxanes such as availability, low toxicity, ease of handling, high stability, and environmental benignity under mild reaction conditions, thus opening a new approach to practical C-N bond formation.

Simple liquid crystal display backlight unit comprising only a single-sheet micropatterned polydimethylsiloxane (PDMS) light-guide plate.

A simple liquid crystal display (LCD) backlight unit (BLU) comprising only a single-sheet polydimethylsiloxane (PDMS) light-guide plate (LGP) has been developed. The PDMS LGP, having micropatterns with an inverse-trapezoidal cross section, was fabricated by backside 3-D diffuser lithography followed by PDMS-to-PDMS replication. The fabricated BLU showed an average luminance of 2878 cd/m(2) with 73.3% uniformity when mounted in a 5.08 cm backlight module with four side view 0.85cd LEDs. The developed BLU can greatly reduce the cost and thickness of LCDs, and it can be applied to flexible displays as a flexible light source due to the flexible characteristic of the PDMS itself.

Experimental induction of anterior disk displacement of the rabbit craniomandibular joint: an immuno-electron microscopic study of collagen and proteoglycan occurrence in the condylar cartilage.

BACKGROUND: Results from our previous studies suggest that surgical induction of anterior disk displacement (ADD) in the rabbit craniomandibular joint (CMJ) leads to histopathological alterations consistent with osteoarthritis. In addition, molecular changes in collagens and glycosaminoglycans (GAGs) were observed using immunohistochemistry. The purpose of the present study was to further characterize those molecular changes in collagens and GAGs using immuno-electron microscopy. METHODS: The right joint of 15 rabbits was exposed surgically and all discal attachments were cut except for the posterior attachment (the bilaminar zone). The disc was then repositioned anteriorly and sutured to the zygomatic arch. The left joint was used as a sham-operated control. Ten additional joints were used as non-operated controls. Mandibular condyles were removed 2 weeks following surgery and processed for light and immuno-electron microscopy using colloidal gold-labeled antibodies against collagen type I, II, VI and IX and against keratan sulfate, chondroitin-4 and -6-sulfate, and link protein. RESULTS: Light microscopic results showed osteoarthritic changes. Immuno-electron microscopy of osteoarthritic cartilage demonstrated a decline in type II collagen, the abnormal presence of type I collagen and loss of type VI and IX collagens. Quantitative colloidal gold immuno-electron microscopy confirmed the depletion of keratan sulfate, chondroitin-4 and -6-sulfate, and link protein in osteoarthritic cartilage. CONCLUSION: Anterior disk displacement leads to molecular alterations in both the collagen and the proteoglycans of rabbit condylar cartilage characteristic of osteoarthritis in other synovial joints. These alterations are consistent with loss of the shock absorber function of the cartilage and injury of the underlying bone.