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1.

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.

Objective

We investigated the efficacy of a flexible light-emitting diode (LED) unit that emits multiple wavelengths to improve PDT effects.

Methods

HaCaT cells were incubated with 5-ALA and subsequently irradiated with either a single wavelength or sequentially with two wavelengths. Cell viability and reactive oxygen species were analyzed. Nude mice were implanted with COLO679 cells by subcutaneous injection into the flank. 5-ALA was subcutaneously injected into the tumor. The tumor was irradiated with 50?J/cm2 (day 0) and assessed daily until day 21.

Results

The synergistic PDT effects of dual-wavelength irradiation and reactive oxygen species production were highest with the 405-nm and 505-nm wavelength combination. This dual wavelength combination was also the most effective in vivo.

Conclusion

We could therefore conclude that dual-wavelength PDT is an efficient strategy for improving the therapeutic effects of PDT. Using a flexible LED unit is expected to achieve more uniform irradiation of uneven areas.  相似文献   
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Background

In a pooled analysis of the phase 3 Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment I (COMFORT-I) and COMFORT-II clinical trials, adult patients with intermediate-2 or high-risk myelofibrosis who received oral ruxolitinib at randomization or after crossover from placebo or best available therapy (BAT) had improved overall survival (OS).

Methods

This post hoc analysis of pooled COMFORT data examined relevant disease outcomes based on the disease duration (≤12 or >12 months from diagnosis) before ruxolitinib initiation.

Results

The analysis included 525 patients (ruxolitinib: ≤12 months, n = 84; >12 months, n = 216; placebo/BAT: ≤12 months, n = 66; >12 months, n = 159); the median age was 65.0–70.0 years. Fewer thrombocytopenia and anemia events were observed among patients who initiated ruxolitinib treatment earlier. At Weeks 24 and 48, the spleen volume response (SVR) was higher for patients who initiated ruxolitinib earlier (47.6% vs. 32.9% at Week 24, p = .0610; 44.0% vs. 26.9% at Week 48, p = .0149). In a multivariable analysis of factors associated with spleen volume reduction, a logistic regression model that controlled for confounding factors found that a significantly greater binary reduction was observed among patients with shorter versus longer disease duration (p = .022). At Week 240, OS was significantly improved among patients who initiated ruxolitinib earlier (63% [95% CI, 51%‒73%] vs. 57% [95% CI, 49%‒64%]; hazard ratio, 1.53; 95% CI, 1.01‒2.31; p = .0430). Regardless of disease duration, a longer OS was observed for patients who received ruxolitinib versus those who received placebo/BAT.

Conclusions

These findings suggest that earlier ruxolitinib initiation for adult patients with intermediate-2 and high-risk myelofibrosis may improve clinical outcomes, including fewer cytopenia events, durable SVR, and prolonged OS.

Plain Language Summary

  • Patients with myelofibrosis, a bone marrow cancer, often do not live as long as the general population. These patients may also have an enlarged spleen and difficult symptoms such as fatigue.
  • Two large clinical trials showed that patients treated with the drug ruxolitinib lived longer and had improved symptoms compared to those treated with placebo or other standard treatments.
  • Here it was examined whether starting treatment with ruxolitinib earlier (i.e., within a year of diagnosis) provided benefits versus delaying treatment.
  • Patients who received ruxolitinib within a year of diagnosis lived longer and experienced fewer disease symptoms than those whose treatment was delayed.
  相似文献   
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ABSTRACT

Abortion is legal in South Africa, but negative abortion attitudes remain common and are poorly understood. We used nationally representative South African Social Attitudes Survey data to analyze abortion attitudes in the case of fetal anomaly and in the case of poverty from 2007 to 2016 (n = 20,711; ages = 16+). We measured correlations between abortion attitudes and these important predictors: religiosity, attitudes about premarital sex, attitudes about preferential hiring and promotion of women, and attitudes toward family gender roles. Abortion acceptability for poverty increased over time (b = 0.05, p < .001), but not for fetal anomaly (b = ?0.008, p = .284). Highly religious South Africans reported lower abortion acceptability in both cases (Odds Ratio (OR)anomaly = 0.85, p = .015; ORpoverty = 0.84, p = .02). Premarital sex acceptability strongly and positively predicted abortion acceptability (ORanomaly = 2.63, p < .001; ORpoverty = 2.46, p < .001). Attitudes about preferential hiring and promotion of women were not associated with abortion attitudes, but favorable attitudes about working mothers were positively associated with abortion acceptability for fetal anomaly ((ORanomaly = 1.09, p = .01; ORpoverty = 1.02, p = .641)). Results suggest negative abortion attitudes remain common in South Africa and are closely tied to religiosity, traditional ideologies about sexuality, and gender role expectations about motherhood.  相似文献   
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