Alternative Splicing of the Chromodomain Protein Morf4l1 Pre-mRNA Has Implications on Cell Differentiation in the Developing Chicken Retina

The proliferation, cell cycle exit and differentiation of progenitor cells are controlled by several different factors. The chromodomain protein mortality factor 4-like 1 (Morf4l1) has been ascribed a role in both proliferation and differentiation. Little attention has been given to the existence of alternative splice variants of the Morf4l1 mRNA, which encode two Morf41l isoforms: a short isoform (S-Morf4l1) with an intact chromodomain and a long isoform (L-Morf4l1) with an insertion in or in the vicinity of the chromodomain. The aim of this study was to investigate if this alternative splicing has a function during development. We analysed the temporal and spatial distribution of the two mRNAs and over-expressed both isoforms in the developing retina. The results showed that the S-Morf4l1 mRNA is developmentally regulated. Over-expression of S-Morf4l1 using a retrovirus vector produced a clear phenotype with an increase of early-born neurons: retinal ganglion cells, horizontal cells and cone photoreceptor cells. Over-expression of L-Morf4l1 did not produce any distinguishable phenotype. The over-expression of S-Morf4l1 but not L-Morf4l1 also increased apoptosis in the infected regions. Our results suggest that the two Morf4l1 isoforms have different functions during retinogenesis and that Morf4l1 functions are fine-tuned by developmentally regulated alternative splicing. The data also suggest that Morf4l1 contributes to the regulation of cell genesis in the retina.     

A comparison of feasibility and safety of percutaneous fluoroscopic guided thoracic pedicle screws between Europeans and Asians: is there any difference?

Purpose

To directly compare the safety of fluoroscopic guided percutaneous thoracic pedicle screw placement between Caucasians and Asians.

Methods

This was a retrospective computerized tomography (CT) evaluation study of 880 fluoroscopic guided percutaneous pedicle screws. 440 screws were inserted in 73 European patients and 440 screws were inserted in 75 Asian patients. Screw perforations were classified into Grade 0: no violation; Grade 1: <2 mm perforation; Grade 2: 2–4 mm perforation; and Grade 3: >4 mm perforation. For anterior perforations, the pedicle perforations were classified into Grade 0: no violation, Grade 1: <4 mm perforation; Grade 2: 4–6 mm perforation; and Grade 3: >6 mm perforation.

Results

The inter-rater reliability was adequate with a kappa value of 0.83. The mean age of the study group was 58.3 ± 15.6 years. The indications for surgery were tumor (70.3 %), infection (18.2 %), trauma (6.8 %), osteoporotic fracture (2.7 %) and degenerative diseases (2.0 %). The overall screw perforation rate was 9.7 %, in Europeans 9.1 % and in Asians 10.2 % (p > 0.05). Grade 1 perforation rate was 8.4 %, Grade 2 was 1.2 % and Grade 3 was 0.1 % with no difference in the grade of perforations between Europeans and Asians (p > 0.05). The perforation rate was the highest in T1 (33.3 %), followed by T6 (14.5 %) and T4 (14.0 %). Majority of perforations occurred medially (43.5 %), followed by laterally (25.9 %), and anteriorly (23.5 %). There was no statistical significant difference (p > 0.05) in the perforation rates between right-sided pedicle screws and left-sided pedicle screws (R: 10.0 %, L: 9.3 %).

Conclusions

There were no statistical significant differences in the overall perforation rates, grades of perforations, direction of perforations for implantation of percutaneous thoracic pedicle screws insertion using fluoroscopic guidance between Europeans and Asians. The safety profile for this technique was comparable to the current reported perforation rates for conventional open pedicle screw technique.

     

A comparative study of dydrogesterone and micronized progesterone for luteal phase support during in vitro fertilization (IVF) cycles

The aim of the present study was to compare the efficacy, tolerability and patients’ satisfaction after the use of oral dydrogesterone with vaginal micronized progesterone for luteal-phase support (LPS) among infertile women undergoing in vitro fertilization (IVF). A total of 210 women (aged 20–40 years old) with a history of infertility, who underwent controlled ovarian stimulation for fresh intra-cytoplasmic sperm injection-embryo transfer cycles, were included in the study. Consequently, they were randomized to receive LPS with dydrogesterone 20?mg twice daily (n?=?96) or micronized progesterone 400?mg twice daily at the day of oocyte retrieval (n?=?114). The clinical success rate (31% versus 33%; p?=?0.888), miscarriage rate (5.0% versus 3.0%; p?=?0.721), ongoing pregnancy rate (30.0% versus 30.0%; p?=?1.000), implantation (22.0% versus 24.0%; p?=?0.254) and multiple pregnancy rate (5.30% versus 7.20%; p?=?0.394) were comparable among the two groups. Serum progesterone levels were significantly lower among the patients receiving dydrogesterone than the control group (13.62?±?13.83?ng/ml versus 20.66?±?18.09?ng/ml; p?=?0.001). However, there was no statistically significant difference regarding the patients’ satisfaction (p?=?0.825) and tolerability (0.790) between the two groups. Our results showed that oral dydrogesterone (40?mg/day) is as effective as vaginal micronized progesterone considering its clinical outcomes and patients’ satisfaction and tolerability, for LPS among women undergoing IVF.     

An electronic nose in the discrimination of patients with asthma and controls

BACKGROUND: Exhaled breath contains thousands of volatile organic compounds (VOCs) that could serve as biomarkers of lung disease. Electronic noses can distinguish VOC mixtures by pattern recognition. OBJECTIVE: We hypothesized that an electronic nose can discriminate exhaled air of patients with asthma from healthy controls, and between patients with different disease severities. METHODS: Ten young patients with mild asthma (25.1 +/- 5.9 years; FEV(1), 99.9 +/- 7.7% predicted), 10 young controls (26.8 +/- 6.4 years; FEV(1), 101.9 +/- 10.3), 10 older patients with severe asthma (49.5 +/- 12.0 years; FEV(1), 62.3 +/- 23.6), and 10 older controls (57.3 +/- 7.1 years; FEV(1), 108.3 +/- 14.7) joined a cross-sectional study with duplicate sampling of exhaled breath with an interval of 2 to 5 minutes. Subjects inspired VOC-filtered air by tidal breathing for 5 minutes, and a single expiratory vital capacity was collected into a Tedlar bag that was sampled by electronic nose (Cyranose 320) within 10 minutes. Smellprints were analyzed by linear discriminant analysis on principal component reduction. Cross-validation values (CVVs) were calculated. RESULTS: Smellprints of patients with mild asthma were fully separated from young controls (CVV, 100%; Mahalanobis distance [M-distance], 5.32), and patients with severe asthma could be distinguished from old controls (CVV, 90%; M-distance, 2.77). Patients with mild and severe asthma could be less well discriminated (CVV, 65%; M-distance, 1.23), whereas the 2 control groups were indistinguishable (CVV, 50%; M-distance, 1.56). The duplicate samples replicated these results. CONCLUSION: An electronic nose can discriminate exhaled breath of patients with asthma from controls but is less accurate in distinguishing asthma severities. CLINICAL IMPLICATION: These findings warrant validation of electronic noses in diagnosing newly presented patients with asthma.     

Epithelial differentiation is a determinant in the production of eotaxin-2 and -3 by bronchial epithelial cells in response to IL-4 and IL-13

The composition of the airway epithelium is dynamic and epithelial differentiation is regulated by endogenous mediators as well as inhaled substances. In atopic asthma the differentiation of the epithelium is altered. Various studies have addressed the ability of cultured airway epithelial cells to release the eosinophil-attractant chemokines eotaxin, eotaxin-2 and eotaxin-3 using epithelial cell lines or poorly differentiated primary cells. Since little is known about the role of the epithelial differentiation state in the response of epithelial cells to stimuli that increase production of mediators such as the eotaxins, we analyzed the effect of differentiation state on the production of the eotaxins. In particular, we investigated the effects of the Th2 cytokines IL-4 and IL-13 on eotaxin-2 and -3 production by primary human bronchial epithelial cells and examined whether their production is affected by epithelial cell differentiation using both submerged and air-liquid interface (ALI) cultures. The results show that both IL-4 and IL-13 increase eotaxin-2 and -3 mRNA expression and protein release in submerged- and ALI-cultures. Moreover, epithelial differentiation in ALI-cultures appeared an important determinant in the regulation of eotaxin-2 and -3. Mucociliary differentiation of the epithelial cells was induced by culture in the presence of a high concentration of retinoic acid (RA), whereas low concentrations of RA resulted in a flattened squamous epithelial phenotype. Mucociliary differentiated ALI-cultures expressed and released more eotaxin-3 upon stimulation with IL-4/IL-13, whereas eotaxin-2 production was predominantly found in squamous differentiated ALI-cultures. TNFalpha reduced IL-4-induced eotaxin-2 release in submerged cultures but not in ALI-cultures; no effects on eotaxin-3 synthesis were observed. The results indicate that epithelial differentiation is an important determinant in Th2 cytokine-induced eotaxin-2 and -3 release by airway epithelial cells. These findings may provide new insights into the role of airway epithelial differentiation and Th2 cytokines in the pathogenesis of inflammatory lung disorders such as asthma.     

Attitudes, awareness and perceptions on evidence based dentistry and scientific publications among dental professionals in the county of Halland, Sweden: a questionnaire survey

The objective was to identify dental professionals' attitudes and awareness on evidence based dentistry (EBD), and to elucidate perceived barriers and views on how to move towards EBD. A questionnaire was sent to 290 dental professionals (dental hygienists, general dentists, specialist dentists) in the county of Halland, Sweden. The questionnaire consisted of closed questions and free text sections, related to attitudes, awareness and skills on databases, EBD, and terms related to scientific publications, as well as perceived barriers towards EBD. A majority of the respondents had a welcoming attitude towards EBD. The respondents perceived their colleagues less positive towards EBD. The respondents considered EBD, at least partly, useful in daily dental practice. With the exception of general dentists in private practice, a vast majority of the dental professionals thought that EBD would improve the care of their patients. Dental professionals in the county of Halland, in Sweden, had a welcoming attitude towards EBD, and indicated an open attitude for learning more about interpretation of evidence from scientific publications. The most commonly perceived barriers towards EBD, were 'lack of time' and 'poor availability of evidence'.