Dual wavelength 5-aminolevulinic acid photodynamic therapy using a novel flexible light-emitting diode unit

Background

Photosensitizers used for photodynamic therapy (PDT) to treat dermatologic disease are metabolized into mainly protoporphyrin IX (PpIX), which has five absorption wavelength peaks: 410?nm, 510?nm, 545?nm, 580?nm, and 630?nm. Although only red light around 635?nm and blue light around 400?nm are used as light sources for PDT, the efficiency of PDT might be improved by using multiple wavelengths, including those that correspond to the other absorption peaks of PpIX. Furthermore, because the target disease often occurs on the face, a flexible-type light-source unit that can be fitted to the lesion without unnecessarily exposing the mucous membranes, e.g., the eyes, nostrils, and mouth, is preferred.

Standard versus customised locking plates for fixation of schatzker ii tibial plateau fractures

Aim3D-printed implants could improve the capture of fracture fragments for improved stability of tibial plateau fracture fixation. The aim of this study was to compare the biomechanical strength of fixation constructs using standard and customised 3D-printed proximal tibial locking plates for fixation of tibial plateau fractures.MethodsThis is a biomechanical study utilising six pairs of cadaveric tibiae. Fractures were created in an identical fashion using an osteotome and mallet, and fixed using either a standard, commercially-available proximal tibia locking plate or a customised 3D-printed plate. Design and production of the customised plates followed a “3D printing at point-of-care” model. Customised stainless steel 316 L plates were produced within a local additive manufacturing laboratory based upon pre-operative CT scans. Determination of implant choice within each cadaver pair was performed via simple randomisation. Following fracture fixation, the tibiae were skeletalised and biomechanically tested using a customised loading jig and a size-matched femoral knee prosthesis. The constructs were loaded cyclically from 100 N to approximately three times the cadaveric body-weight at 5 Hz for 10 000 cycles. Every 1000 cycles, the test was paused and the tibia was physically checked for failure. If failure had not occurred by the end of the testing cycle, the construct was loaded to failure and the load at which the construct failed was noted.ResultsFixation constructs using the 3D-printed plates performed comparably to those using the standard plates. There was no significant difference in the degree of fracture fragment displacement in both constructs. Overall longitudinal construct stiffness and load to failure was higher in the 3D-plates group but this did not reach statistical significance.ConclusionProduction of customised plates for proximal tibia fractures at point-of-care is feasible, however fixation constructs with these plates did not provide any biomechanical advantage over standard plates in terms of axial loading stiffness.     

Low-dose all-trans retinoic acid enhances cytotoxicity of cisplatin and 5-fluorouracil on CD44+ cancer stem cells

Cis-diamminedichloridoplatinum(II)(CDDP)-based combination chemotherapy is frequently used in gastrointestinal cancer. The synergistic mechanism of all-trans retinoic acid (ATRA), cisplatin (CDDP) and 5-fluorouracil (5-FU) in combination remains unclear. Despite their potent antitumor properties, resistance to CDDP and 5-FU develops frequently in tumors. To clarify this mechanism, we determined the sensitivity to each drug and their combination in two gastrointestinal cancer stem cells (CSCs) subpopulation.Here, we report the identification and separation of CD44⁺ cells from human gastric carcinoma (AGS) and human esophageal squamous cell carcinoma (KYSE-30) cancer cell lines by magnetic activated cell sorting (MACS). We allowed the CD44^± cells to grow 6 days at a subtoxic concentration of ATRA and then treated with different concentration of CDDP and 5-FU for 24 h. The cytotoxicity was examined by cell proliferation MTT assay. Additionally, AO/EB staining was used for detection of apoptotic cells. In order to determine whether the growth inhibition was also associated with changes in cell cycle distribution, cell cycle analysis was performed using flow cytometry.Low concentration of ATRA (1 μM, 6days) followed by 5-FU and CDDP was found to be more effective than either drugs alone, thus resulting in synergistic cytotoxicity in Kyse-30 and AGSCD44^± cells. Furthermore, there was an indication that the combination of ATRA with 5FU and CDDP caused an increase in cell cycle arrest in G2/M and G0/G1.We conclude that low concentration of ATRA enhances the cytotoxicity of CDDP and 5FU by facilitating apoptosis and cell cycle arrest in gastrointestinal CSCs and provide a rational basis for the design of novel, well-tolerated CDDP- and 5FU-based chemotherapy in human gastrointestinal carcinoma.     

Evaluating the inhibitory potential of Withania somnifera on platelet aggregation and inflammation enzymes: An in vitro and in silico study

Context Withania somnifera (L.) Dunal is traditionally used for treating various ailments, but lacks scientific evaluation.

Objective This study evaluates Withania somnifera (WS) for its effect on platelet activity and inflammatory enzymes.

Materials and methods Aqueous and ethanolic (1:1) leaf extracts were subjected to in vitro indirect haemolytic activity using Naja naja venom, human platelet aggregation was quantified for lipid peroxidation using arachidonic acid (AA) as agonist and 5-lipoxygenase (5-LOX) levels were determined using standard spectrometric assays. Further, molecular docking was performed by the ligand fit method using molegro software package (Molegro ApS, Aarhus, Denmark).

Results The study found that aqueous and ethanol extracts have very negligible effect (15%) with an IC₅₀ value of 13.8?mg/mL on PLA₂ from Naja naja venom. Further, extracts of WS also had very little effect (18%) with an IC₅₀ value of 16.6?mg/mL on malondialdehyde (MDA) formation. However, a 65% inhibition of 5-LOX with an IC₅₀ value of 0.92?mg/mL was observed in 1:1 ethanol extracts. The same was evident from SAR model with the active ingredient withaferin A binding predominantly on Phe 77, Tyr 98, Arg 99, Asp 164, Leu 168, Ser 382, Arg 395, Tyr 396 and Tyr 614 with an atomic contact energy value of??128.96 compared to standard phenidone (?103.61). Thus, the current study validates the application of WS for inflammatory diseases.

Conclusion This study reveals the inhibitory potential of W. somnifera on inflammatory enzymes and platelet aggregation. Thus, WS can serve as a newer, safer and affordable medicine for inflammatory diseases.     

Infecciones de transmisión sexual en hombres internos en prisión: riesgo de desarrollo de nuevas infecciones

ObjectiveTo measure incidence and main risk factors related to sexually transmitted infections (STIs) in Daroca Prison (Zaragoza, Spain).MethodA retrospective cohort study (2005-2013) to measure the incidence of STI and a cross-sectional study to measure risk factors.ResultsOf the 203 inmates, 79 developed an STI, 37 had a previous STI, 55.2% lacked knowledge on STI prevention, and 28.9% showed behaviours unfavourable for STI prevention. The incidence rate was 6.5 STIs per 1,000 inmates-year. The most frequent STIs were hepatitis B (39.7%), Ureaplasma urealyticum (19.1%), herpes simplex (16.2%) and HIV (8.8%). The risk (hazard ratio, HR) of acquiring a new STI was significantly higher in inmates with a history of previous STI (HR = 2.61; 95%CI: 1.01 to 6.69), and was at the limit of significance for non-preventive behaviour (HR = 2.10; 95%CI: 0.98 to 4.53), but not in knowledge related to STIs (HR = 1.33; 95%CI: 0.58 to 3.07).ConclusionThe most important risk factors in prison are behaviours related to STIs and previous history of STIs. Other factors are being a repeat offender, injecting drug use, or being in a methadone programme. Health personnel and peer education can facilitate prevention and control.