Protein Content and Methyl Donors in Maternal Diet Interact to Influence the Proliferation Rate and Cell Fate of Neural Stem Cells in Rat Hippocampus

Maternal diet during pregnancy and early postnatal life influences the setting up of normal physiological functions in the offspring. Epigenetic mechanisms regulate cell differentiation during embryonic development and may mediate gene/environment interactions. We showed here that high methyl donors associated with normal protein content in maternal diet increased the in vitro proliferation rate of neural stem/progenitor cells isolated from rat E19 fetuses. Gene expression on whole hippocampi at weaning confirmed this effect as evidenced by the higher expression of the Nestin and Igf2 genes, suggesting a higher amount of undifferentiated precursor cells. Additionally, protein restriction reduced the expression of the insulin receptor gene, which is essential to the action of IGFII. Inhibition of DNA methylation in neural stem/progenitor cells in vitro increased the expression of the astrocyte-specific Gfap gene and decreased the expression of the neuron-specific Dcx gene, suggesting an impact on cell differentiation. Our data suggest a complex interaction between methyl donors and protein content in maternal diet that influence the expression of major growth factors and their receptors and therefore impact the proliferation and differentiation capacities of neural stem cells, either through external hormone signals or internal genomic regulation.     

Choroidal structural changes determined by the binarization method after intravitreal aflibercept treatment in neovascular age-related macular degeneration

AIM: To assess the choroidal structural alterations after intravitreal injection of aflibercept in neovascular age-related macular degeneration (nAMD). METHODS: Fifty eyes with treatment-naïve nAMD were evaluated at baseline, 3rd, and 12th month. Fifty eyes of 50 healthy subjects were also included as controls. Choroidal thickness (CT) was measured in the subfoveal region. Total circumscribed choroidal area (CA), luminal area (LA), stromal area (SA), and choroidal vascularity index (CVI) was calculated using Image J. RESULTS: At baseline, subfoveal CT was increased in nAMD patients compared to controls (P=0.321). Eyes with nAMD had a significantly increased total circumscribed CA and SA (P=0.041, 0.005, respectively). The CVI was decreased (P=0.038). In the 3rd month, the subfoveal CT, LA, and CVI revealed a decrease (P=0.005, P=0.039, 0.043, respectively). In the 12th month, subfoveal CT, LA, and CVI were decreased in comparison to baseline measures (P<0.001, 0.006, 0.010, respectively). CONCLUSION: Significant structural alterations are found after intravitreal aflibercept treatment during the 12-month follow-up, in particular at the third month, in eyes with nAMD.     

外周血CD4+CXCR5+Tfh水平对肺炎克雷伯菌感染者预后的影响

目的　检测肺炎克雷伯菌感染者外周血CD4+CXCR5+滤泡辅助性T细胞（T follicular helper cell, Tfh）水平，探讨其对患者预后的影响。方法　选取2017年7月—2019年5月于本院ICU住院治疗的147例患者为研究对象，根据患者入院后是否出现肺炎克雷伯菌感染，将其分为感染组（69例）和未感染组（78例）。采用流式细胞术检测147例患者外周血CD4+CXCR5+Tfh水平。采用单因素分析肺炎克雷伯菌感染的影响因素；采用单因素分析和多因素Logistic回归分析肺炎克雷伯菌感染者预后的影响因素。结果　感染组的住院时间、入住ICU时间、入住ICU时APACHE II评分、机械通气时间及心血管疾病、多器官功能障碍综合征、接受手术、恶性肿瘤患者比例均高于未感染组，差异均有统计学意义（P均＜0.05）。感染组外周血CD4+CXCR5+Tfh水平、死亡患者比例均高于未感染组（P均＜0.05）。感染组中死亡患者外周血CD4+CXCR5+Tfh水平高于生存患者（P＜0.05）。CD4+CXCR5+Tfh、碳青霉烯类耐药、入住ICU时APACHE II评分是影响肺炎克雷伯菌感染者死亡的独立危险因素（P均＜0.05）。结论　外周血CD4+CXCR5+Tfh水平在肺炎克雷伯菌感染者中显著升高，CD4+CXCR5+Tfh可能通过参与机体免疫应答影响感染者的预后。检测CD4+CXCR5+Tfh水平不仅对判断感染者的免疫状态有重要意义，也可为肺炎克雷伯菌感染者治疗提供依据。     

Microdensitometry of osteopontin as an immunohistochemical prognostic biomarker in colorectal carcinoma tissue microarrays: potential and limitations of the method in ‘biomarker pathology’

Prall F, Maletzki C & Linnebacher M
(2012) Histopathology  61, 823–832 Microdensitometry of osteopontin as an immunohistochemical prognostic biomarker in colorectal carcinoma tissue microarrays: potential and limitations of the method in ‘biomarker pathology’ Aims: To explore the potential and limitations of ‘biomarker pathology’ with quantitative immunohistochemistry on tissue microarrays, taking osteopontin and colorectal carcinoma as a model system. Methods and results: Microdensitometry for quantitative evaluation of osteopontin immunohistochemistry (clone OP3N) on digital microphotographs using the public domain software ImageJ was observed to be straightforward to perform and reliable. However, using colorectal carcinoma cell lines (n = 11) the correlation between densitometric evaluations of Western blots and microdensitometry of immunocytochemistry of slide cultures was only moderate. A virtual resampling method to simulate tissue microarrays showed that, due to heterogeneity of immunostaining, tumours were misclassified in nearly 20% of the arrays, even if four punches were used. With regard to prognosis, microdensitometric evaluation of a tissue microarray made of a clinicopathologically well‐characterized series of colorectal carcinomas with long‐term follow‐up (222 cases evaluable in the tissue microarray, UICC Stages I–III/R0) showed a moderate survival advantage of patients with high osteopontin expression by microdensitometry. Conclusions: These results challenge the basic assumption that microdensitometry is a precise technique for the quantification of proteins detected by immunohistochemistry and delineate drawbacks encountered when working with tissue microarrays in clinicopathological studies.     

Surgery for oligometastatic disease in non-small-cell lung cancer

In general, patients with additional metastatic nodules or distant metastases of a non-small-cell lung cancer (NSCLC) have a poor prognosis. However, published results suggest that in carefully selected patients with synchronous or metachronous metastatic lesions, long-term survival can be obtained when a complete resection of the primary site and metastasis – mostly single brain or adrenal – is achieved. Different subgroups of patients with metastatic NSCLC exist and a distinction should be made between additional malignant nodules in the ipsilateral and contralateral lung, malignant pleural effusion and extrathoracic, single or multiple metastases. Patients with additional malignant nodules in the same lobe or ipsilateral nonprimary lobe have a better prognosis than suggested by the current tumor–node–metastasis (TNM) classification. The other subgroups have a poor prognosis. In view of recent data from a large, international database, proposals have been made for the new TNM classification that will be introduced in 2009.     

Medical gases

Understanding the complex process of production, storage and delivery of medical gases is vitally important to ensure safe and efficient practice by anaesthetists. This article discusses the medical gases commonly used in anaesthesia and intensive care and details the journey of the commonly used medical gases from production to patient delivery. It includes core knowledge for the FRCA.     

Impact of disease severity on work productivity and activity impairment in Japanese patients with atopic dermatitis

Atopic dermatitis (AD) is a common inflammatory skin disease that is characterized by chronic and persisting pruritic and eczematous lesions. There has been no study of work productivity and activity in AD patients in relation to disease severity. The purpose of this study was to examine the impact of disease severity on work productivity and activity impairment (WPAI) in adult AD patients using the Japanese version of the questionnaire. Data were collected from 112 AD patients who visited the Jikei University Hospital. Outcomes as measured by the questionnaire included employment status, total work productivity impairment (TWPI) and total activity impairment (TAI). We investigated the correlation between TWPI or TAI scores and severity scoring of AD (SCORAD) for disease severity and dermatology life quality index (DLQI) for quality of life impairment. Both TWPI and TAI scores were significantly correlated with the SCORAD and DLQI scores (P < 0.001), indicating disease severity is significantly associated with WPAI in Japanese adult AD patients. Further studies are necessary to evaluate the effects of treatments on WPAI for severe AD patients.