A catch‐up validation study of an in vitro skin irritation test method using reconstructed human epidermis LabCyte EPI‐MODEL24

Three validation studies were conducted by the Japanese Society for Alternatives to Animal Experiments in order to assess the performance of a skin irritation assay using reconstructed human epidermis (RhE) LabCyte EPI‐MODEL24 (LabCyte EPI‐MODEL24 SIT) developed by the Japan Tissue Engineering Co., Ltd. (J‐TEC), and the results of these studies were submitted to the Organisation for Economic Co‐operation and Development (OECD) for the creation of a Test Guideline (TG). In the summary review report from the OECD, the peer review panel indicated the need to resolve an issue regarding the misclassification of 1‐bromohexane. To this end, a rinsing operation intended to remove exposed chemicals was reviewed and the standard operating procedure (SOP) revised by J‐TEC. Thereafter, in order to confirm general versatility of the revised SOP, a new validation management team was organized by the Japanese Center for the Validation of Alternative Methods (JaCVAM) to undertake a catch‐up validation study that would compare the revised assay with similar in vitro skin irritation assays, per OECD TG No. 439 (2010). The catch‐up validation and supplementary studies for LabCyte EPI‐MODEL24 SIT using the revised SOPs were conducted at three laboratories. These results showed that the revised SOP of LabCyte EPI‐MODEL24 SIT conformed more accurately to the classifications for skin irritation under the United Nations Globally Harmonised System of Classification and Labelling of Chemicals (UN GHS), thereby highlighting the importance of an optimized rinsing operation for the removal of exposed chemicals in obtaining consistent results from in vitro skin irritation assays. Copyright © 2013 John Wiley & Sons, Ltd.     

Mothers’ alexithymia,depression and anxiety levels and their association with the quality of mother-infant relationship: A preliminary study

Objective. To evaluate the relationship between mothers and their developmentally normal infants in terms of maternal alexithymia, depression and anxiety, and marital satisfaction. Methods. Fifty children between 18 and 48 months of age, and their mothers, were referred consecutively to the Infant Mental Health Unit of Ankara University School of Medicine, Department of Child and Adolescent Psychiatry. The sociodemographic features of the families and the depressive symptoms, anxiety, marital satisfaction and alexithymia levels of the mothers were assessed. The relationships between children in normal developmental stages and their mothers were evaluated and rated using a structured clinical procedure. Results. There was a negative correlation between the mothers’ alexithymia scores and the quality of the mother-infant relationship (p < 0.05). Mothers with high alexithymia showed higher depression and lower relationship qualities than mothers with low alexithymia, according to the correlation analysis. When depression and anxiety were controlled, high alexithymia levels were predictive of a low, impaired mother-infant relationship. Conclusion. Since alexithymia is a trait-like variable which has a negative correlation with impairment in a mother-infant relationship, it must be investigated in the assessment of mothers’ interactions with their babies.     

Stabilization and encapsulation of photosensitive resveratrol within yeast cell

The photosensitive resveratrol was successfully encapsulated in yeast cells for the first time, as characterized by FT-IR spectra, fluorescence and confocal micrographs of the yeast cells, resveratrol and microcapsules. The release characteristic of the obtained yeast-encapsulated resveratrol in simulated gastric fluid was evaluated, and its storage stability as a powder was investigated at 25 degrees C/75% relative humidity (RH), 25 degrees C/90% RH and 60 degrees C under the laboratory fluorescent lighting conditions (ca. 300 lx) or in the dark. Also, the scavenging capacity of yeast-encapsulated resveratrol on DPPH radical was compared with that of non-encapsulated resveratrol. It could be demonstrated clearly that no chemical changes occurred during the encapsulation. Besides, the DPPH radical-scavenging activity increased after the encapsulation. In addition, the yeast-encapsulated resveratrol exhibited good stability, and its bioavailability was enhanced as a result of increased solubility of resveratrol and sustained releasing.     

Seasonal variation of human sperm cells among 4,422 semen samples: A retrospective study in Turkey

We aimed to assess the possible presence of a seasonal pattern in three parameters of semen analysis: sperm concentration, morphology, and motility as a function of the time of ejaculation and sperm production (spermatogenesis) in normal and oligozoospermic men. This retrospective study included a consecutive series of 4,422 semen samples that were collected from patients as a part of the basic evaluation of the infertile couples attending the Reproductive Endocrine Outpatient Clinic of a tertiary women’s hospital in Ankara, Turkey, between January 1, 2012 and December 31, 2013. The samples were classified according to sperm concentration: ≥15 x10⁶/mL as normozoospermic samples and 4 -14.99 x10⁶/mL as oligozoospermic samples and seasonal analysis of the semen samples were carried out separately. When the data was analyzed according to the season of semen production, there was no seasonal effect on the sperm concentration. A gradual and consistent decrease in the rate of sperm with fast forward motility was observed from spring to fall with a recovery noticed during the winter. The percentage of sperms with normal morphology was found to be statistically significantly higher in the spring samples compared with the summer samples (p=0.001). Both normozoospermic and oligozoospermic semen samples appeared to have better sperm parameters in spring and winter. The circannual variation of semen parameters may be important in diagnosis and treatment desicions.

Abbreviations: WHO: World Health Organization; mRNA:messenger ribonucleic acid     

气囊导尿管在鼻出血后鼻孔填塞治疗中的应用

目的 介绍双腔气囊导尿管在鼻出血治疗中的应用方法及并发症的预防.方法 对我院2003 ～ 2010年接受双腔气囊导尿管后鼻孔填塞治疗的96例鼻出血患者进行临床分析.结果 96例患者全部治愈,治愈率100％.1例因导尿管压迫前鼻孔致前鼻孔狭窄,其余均未见明显并发症.结论 双腔气囊导尿管后鼻孔填塞,是治疗鼻出血的一种安全可靠的方法.操作中注意细节,可防止并发症的发生.     

Two cases of pulmonary aspergillosis successfully treated with combinated micafungin and itraconazole therapy

We report 2 cases of pulmonary aspergillosis treated successfully by combining micafungin and traconazole. Case 1: A 51-year-old man with hemoptysis and dyspnea on effort treated for pulmonary tuberculosis and aspergillosis was found on chest CT on admission to have a fungus ball in the left upper lobe and increasing consolidation around the cavity of both lung fields. Bronchoscopy proved positive for aspergillus PCR in bronchial lavage. He was diagnosed with chronic necrotizing pulmonary aspergillosis, based on clinical and radiological findings and the positive reaction for aspergillus PCR. He was treated with micafungin alone at first, this proved ineffective, so itraconazole was added, resulting in improvement. Case 2: A 24-year-old woman with stabilized Hodgkin's disease (mixed). She had suffered from a cough and back pain, and chest CT showed increasing consolidation inside and around a giant bulla. She was diagnosed with chronic necrotizing pulmonary aspergillosis, based on isolation for Aspergillus sp. in sputum culture and a positive reaction for Aspergillus antigen in bronchial lavage and Aspergillus antibody in serum. She was treated with the combined micafungin and itraconazole, which rapidly improved symptoms and radiological findings. Pulmonary aspergillosis therapy is often difficult, because delivery of the drug to the infection site is limited and drug tolerance is poor. We found that combination micafungin and itraconazole therapy is tolerable and effective in these cases.     

Leveraging Computerized Sign-Out to Increase Error Reporting and Addressing Patient Safety in Graduate Medical Education

SUMMARY Setting Electronic reporting systems are important components of the patient-safety movement but have been problematic particularly in capturing information from physicians. Objective In an attempt to increase error reporting in our community hospital residency program, we devised a convenient safety log integrated into the computerized resident-patient sign-out. Measurements and Main Results Safety-log events are discussed in weekly safety reports with emphasis on developing a safety culture and preventing further events. We report our experience implementing the safety log. The program quadrupled our contribution to the hospital quality assurance system and has led to significant system innovations. Challenges have included sharing information and improving accountability without humiliating participants or alienating co-workers, as well as sustaining the project over time. Conclusion Residents are uniquely placed to provide insight into hospital systems. An error-reporting system based in a resident sign-out can leverage this role into an important tool for safety education and care improvement.     

Curettage and multiple needle puncture-assisted methyl-aminolaevulinate photodynamic therapy of basal cell carcinoma

Background

The use of skin puncture techniques may facilitate the delivery of topically applied drugs for photodynamic therapy (PDT).

Objectives

The main aim of this prospective study was to evaluate the efficacy and cosmetic outcome of curettage, multiple needle puncture, and methyl-aminolaevulinate (MAL)-PDT in basal cell carcinoma (BCC).

Materials and methods

All tumours received curettage and 15-20 needle punctures/cm² before two sessions of MAL-PDT. The primary endpoint was clinically observed recurrence at follow-up. Overall, 284 patients with 299 histologically verified BCC (70 superficial, 190 nodular, 35 aggressive, and four not subtyped) were included. Following PDT, the mean follow-up period was 6.7 months.

Results

After follow-up, 274 (92%) of 299 treatment sites showed no clinical signs of recurrence, with >90% complete response for each BCC subtype. The cosmetic outcome was rated as excellent/good in 81% of cases.

Conclusion

Good short-term treatment results were shown following curettage, multiple needle puncture, and MAL-PDT for BCC of different subtypes.

     

High levels of chromosomal instability facilitate the tumor growth and sphere formation

Most cancer cells show chromosomal instability (CIN), a condition in which chromosome missegregation occurs at high rates. Growing evidence suggests that CIN is not just a consequence of, but a driving force for, oncogenic transformation, although the relationship between CIN and tumorigenesis has not been fully elucidated. Here we found that conventional two‐dimensional (2D) culture of HeLa cells, a cervical cancer‐derived cell line, was a heterogenous population containing cells with different CIN levels. Although cells with high‐CIN levels (high‐CIN cells) grew more slowly compared with cells with low‐CIN levels (low‐CIN cells) in 2D monolayer culture, they formed tumors in nude mice and larger spheres in three‐dimensional (3D) culture, which was more representative of the in vivo environment. The duration of mitosis was longer in high‐CIN cells, reflecting their higher mitotic defects. Single‐cell genome sequencing revealed that high‐CIN cells exhibited a higher karyotype heterogeneity compared with low‐CIN cells. Intriguingly, the karyotype heterogeneity was reduced in the spheres formed by high‐CIN cells, suggesting that cells with growth advantages were selected, although genomic copy number changes specific for spheres were not identified. When we examined gene expression profiles, genes related to the K‐ras signaling were upregulated, while those related to the unfolded protein response were downregulated in high‐CIN cells in 3D culture compared with 2D culture, suggesting the relevance of these genes for their survival. Our data suggested that, although CIN is disadvantageous in monolayer culture, it promotes the selection of cells with growth advantages under in vivo environments, which may lead to tumorigenesis.