Role of circ-FOXO3 and miR-23a in radiosensitivity of breast cancer

Identifying the radiosensitivity of cells before radiotherapy (RT) in breast cancer (BC) patients allows appropriate switching between routinely used treatment regimens and reduces adverse side effects in exposed patients. In this study, blood was collected from 60 women diagnosed with Invasive Ductal Carcinoma (IDC) BC and 20 healthy women. To predict cellular radiosensitivity, a standard G2-chromosomal assay was performed. From these 60 samples, 20 BC patients were found to be radiosensitive based on the G2 assay. Therefore, molecular studies were finally performed on two equal groups (20 samples each) of patients with and without cellular radiosensitivity. QPCR was performed to examine the expression levels of circ-FOXO3 and miR-23a in peripheral blood mononuclear cells (PBMCs) and RNA sensitivity and specificity were determined by plotting Receiver Operating Characteristic (ROC) curves. Binary logistic regression was performed to identify RNA involvement in BC and cellular radiosensitivity (CR) in BC patients. Meanwhile, qPCR was used to compare differential RNA expression in the radiosensitive MCF-7 and radioresistant MDA-MB-231 cell lines. An annexin -V FITC/PI binding assay was used to measure cell apoptosis 24 and 48 h after 2 Gy, 4 Gy, and 8 Gy gamma-irradiation. Results indicated that circ-FOXO3 was downregulated and miR-23a was upregulated in BC patients. RNA expression levels were directly associated with CR. Cell line results showed that circ-FOXO3 overexpression induced apoptosis in the MCF-7 cell line and miR-23a overexpression inhibited apoptosis in the MDA-MB-231 cell line. Evaluation of the ROC curves revealed that both RNAs had acceptable specificity and sensitivity in predicting CR in BC patients. Binary logistic regression showed that both RNAs were also successful in predicting breast cancer. Although only circ-FOXO3 has been shown to predict CR in BC patients, circ-FOXO3 may function as a tumor suppressor and miR-23a may function as oncomiR in BC. Circ-FOXO3 and miR-23a may be promising potential biomarkers for BC prediction. Furthermore, Circ-FOXO3 could be a potential biomarker for predicting CR in BC patients.</p

Evaluation of a combined reflectance photoplethysmography and laser Doppler flowmetry surface probe

Photoplethysmographic (PPG) signals were recorded from the fingers of 16 healthy volunteers with periods of timed and forced respiration. The aim of this pilot study was to compare estimations of arterial oxygen saturation (SpO2) recorded using a dedicated pulse oximetry system while subjects were breathing regularly with and without a mouthpiece containing a flow resistor. The experiments were designed to mimic the effects of mechanical ventilation in manaesthetized patients. The effect of estimated airway pressures of ±15 cmH2O caused observable modulation in the recorded red and PPG signals. SpO2 values were calculated from the pre-recorded PPG signals. Mean SpO2 values were 95.4% with the flow resistor compared with 97.3% with no artificial resistance, with statistical significance demonstrated using a Student’s t-test (P = 0.006)

Evaluation of optical interference in a combined measurement system used for assessment of tissue blood flow

A dual-wavelength pulse oximetry system combined with laser Doppler was developed for the assessment of perfusion. Red and infrared PPG and Doppler signals were recorded from a healthy volunteer in three studies at different measurement sites to investigate the interference between PPG and laser Doppler flowmetry (LDF). Good quality photoplethysmographic (PPG) and Doppler signals were detected simultaneously using this combined probe from the skin of the finger. The influence of the PPG light sources on LDF measurements was investigated; also the influence of the LDF light sources to the PPG measurements was studied. In the worst case, the apparent change in PPG amplitude when the LDF system was switched on was less than 8%, and the change in LDF flux amplitude when the PPG system was switched on was 14.7%

Survival and growth response of mesic and dry-site sources of loblolly pine seedlings to cyclic soil moisture deficit

A growth chamber study compared height, biomass, and mortality rate of 4 to 12 old pine L.) seedlings of mesic and dry-site seed sources to 7 cyclic soil moisture stress levels, averaging between -0.3 to -2.4 Soil moisture stress was monitored gravimetrically throughout each dry-down cycle until a predetermined soil moisture potential was reached; soil was then rewatered. Shoot height was measured at two-month interval, from 4 to 12 months after the emergence of the seedlings. The oven dry weight of the seedlings and their roots were used for biomass determination. Mortality was recorded every 2 months throughout the experiment. Dry-site seedlings outgrew mesic seedlings in every soil moisture stress levels. Height growth declined with increasing moisture stress for both seed sources. The most abrupt reduction in height growth occurred between the nonstressed (-0.3 seedlings and those that grew under -0.6 Dry-site source produced more shoot biomass in all soil moisture stress levels

Comparison of knowledge, attitude and practice of Urban and rural households toward iron deficiency anemia in three provinces of Iran

Background: Lack of nutritional knowledge is one of the most important reasons of nutritional problems and consequently improper practice, which can lead to several complications. This study has been designed in order to compare knowledge, attitude and practices of the urban and rural households regarding iron deficiency anemia (IDA) in Boushehr, Golestan and Sistan & Balouchestan provinces in 2004. Methods: The sampling method at household's level in each province was the single-stage cluster sampling with equal size clusters. The necessary data were gathered with a structured questionnaire and via the interviews between the questioners and the eligible people in each household. Comparison of frequency of variables between urban and rural areas were tested by chi square test. Results: A total of 2306 households were selected as overall sample size. In urban areas, people recognized iron food sources better than rural areas. Knowledge level of respondents about vulnerable group for IDA and the favorite attitude of households toward IDA were better in urban areas of Sistan & Blouchestan and Golestan provinces. In Sistan & Balouchestan and Golestan, rural households who drank tea immediately before or after meal was more than urban ones. The majority of pregnant and lactating mothers (except for rural areas of Bushehr) did not take iron supplement regularly. Less than 60 percent of children used iron drop regularly. Conclusion: Knowledge, attitude, and practice levels of households toward IDA were not acceptable. One of the best ways of improving nutritional practice is nutritional education with focus on applying available food resources

Performance of a novel optical sensor for intraoperative assessment of intestinal viability - 'proof of principle' study

Introduction: Objective assessment of intestinal viability during surgery will allow surgeons to make informed decisions on the safety of intestinal anastomosis and to predict anastomotic related complications.1We investigated the performance of a novel dual sensor incorporating two established methods – photoplethysmography (PPG) and laser Doppler flowmetry (LDF) in a ‘proof of principle’ study. Method: Using the new probe, infrared and red PPG amplitude and LDF flux of the bowel surface were recorded by LDF and PPG simultaneously in 30 patients undergoing large bowel resection with or without anastomosis. Each patient had measurements at eight different time points: before and after colonic mobilisation, over the tumour, before and after ligation of major vascular pedicle, immediately before and after anastomosis (+/- 5 min) at distal and proximal limbs. Both laparoscopic and open resectional cases were included. The differences between the mean amplitude and flux between different measurements were analysed. Results: Twenty four laparoscopic and six open bowel resection cases had a total of 121 measurements recorded using the new probe. The mean IR AC amplitude in pre-ligation was 433 (± 189) mV and the mean IR AC in post ligation was 301 (± 152) mV. A statistically significant difference (P = 0.047) was observed between pre-ligation and post-ligation for the mean infrared PPG amplitude (student’s t-test). A considerable difference in mean amplitude between pre and post ligation for the red PPG was also observed (the mean amplitude for the red PPG fell by –25.6%). The amplitude of the infrared PPG increased after anastomosis by 38.2% at the proximal site and by 37.8% at the distal site. The amplitude of the red PPG also increased after anastomosis (by 6.3%) at the proximal site although the equivalent increase was not seen at the distal site. The LDF measurements did not follow the same pattern of the changes seen in PPG amplitude. Conclusion: The preliminary results show that simultaneous PPG/LDF measurements from a combined sensor is feasible and provide useful information on changes in pulse volume and blood flow. Although the differences in PPG amplitude achieved statistical significance, the LDF measurements produced confounding results, perhaps explained by motion artefacts. Further refinements in design of the probe are required to improve the probe-tissue optical interface and reduce motion artefact

Efficacy of flour fortification with folic acid in women of childbearing age in Iran

Background: Flour fortification with folic acid is one of the main strategies for improving folate status in women of childbearing age. No interventional trial on the efficacy of folic acid fortification has been conducted so far in Iran. Objectives: To study the effects of flour fortification with folic acid on any reduction in neural tube defects (NTDs) and folate status of women of childbearing age. Methods: In a longitudinal hospital-based study, 13,361 postpartum women were studied after admission for childbirth before and after fortification. In addition, two cross-sectional surveys were conducted before (2006) and after flour fortification (2008). The cluster sampling method was used and 580 women, 15-49 years old, were studied as a representative sample of Golestan province in the north of Iran. Fasting blood samples were collected to measure serum vitamin B 12, folate and plasma homocysteine. Sociodemographic data, health characteristics and dietary intake were determined. Results: The mean daily intakes of folate from natural food before and after flour fortification were 198.3 and 200.8 μg/day, respectively. The total folate intake increased significantly from 198.3 to 413.7 μg/day after fortification (p < 0.001). Folate intake increased by an average of 226 μg/day from fortified bread. The mean serum folate level increased from 13.6 to 18.1 nmol/l; folate deficiency decreased from 14.3 to 2.3% (p < 0.001). The incidence rate of NTDs declined by 31% (p < 0.01) in the post-fortification period (2.19 per 1,000 births; December 2007 to December 2008) compared to the pre-fortification period (3.16 per 1,000 births; September 2006 to July 2007). Conclusions: Implementation of mandatory flour fortification with folic acid can lead to a significant increase in serum folate and a significant decrease in NTDs. Copyright © 2011 S. Karger AG, Basel

Tacrolimus and mycophenolate mofetil as second-line treatment in autoimmune hepatitis:Is the evidence of sufficient quality to develop recommendations?

BACKGROUND The standard management of autoimmune hepatitis (AIH) is based on corticosteroids, alone or in combination with azathioprine. Second-line treatments are needed for patients who have refractory disease. However, high-quality data on the alternative management of AIH are scarce. AIM To evaluate the efficacy and safety of tacrolimus and mycophenolate mofetil (MMF) and the quality of evidence by using the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). METHODS A systematic review and meta-analysis of the available data were performed. We calculated pooled event rates for three outcome measures: Biochemical remission, adverse events, and mortality, with their corresponding 95% confidence intervals (CI). RESULTS The pooled biochemical remission rate was 68.9% (95%CI: 60.4-76.2) for tacrolimus, and 59.6% (95%CI: 54.8-64.2) for MMF, and rates of adverse events were 25.5% (95%CI: 12.4-45.3) for tacrolimus and 24.1% (95%CI: 15.4-35.7) for MMF. The pooled mortality rate was estimated at 11.5% (95%CI: 7.1-18.1) for tacrolimus and 9.01% (95%CI: 6.2-12.8) for MMF. Pooled biochemical remission rates for tacrolimus and MMF in patients with intolerance to standard therapy were 56.6% (CI: 43.4-56.6) vs 73.5% (CI: 58.1-84.7), and among non-responders were 59.1% (CI: 48.7-68.8) vs 40.8% (CI: 32.3-50.0), respectively. Moreover, the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups. CONCLUSION Tacrolimus and MMF are in practice considered effective for patients with AIH who are non-responders or intolerant to first-line treatment, but we found no high-quality evidence to support this statement

Intraoperative monitoring of intestinal viability: Evaluation of a new combined sensor

A dual wavelength photoplethysmography (PPG) and laser Doppler flowmetry (LDF) sensor was developed to investigate the suitability of these techniques for monitoring bowel viability intraoperatively. Clinical measurements were obtained from thirty patients undergoing bowel surgery. Three measurements were performed at different stages of the operation. The amplitude of infrared PPG decreased from the baseline measurement to the pre-anastomosis measurement by 36% and LDF flux decreased by 21% for the same measurements. An increase of 33% in amplitude for infrared PPG was observed from the pre-anastomotic to post-anastomosis measurement; the equivalent increase was not seen for LDF flux. The results revealed that the sensor could potentially indicate changes in perfusion and blood flow at critical phases of surgery, thereby assisting in the early detection of inadequate blood supply in bowel tissue. The results also suggest that laser Doppler is more sensitive to movement artefact compared to PPG

A solid‐phase transfection platform for arrayed CRISPR screens [Corrigendum]

Since the publication of this study, it has come to our attention that a citation to the study by Bulkescher et al (2017) was omitted from the Introduction. The following sentence should have been included in the introduction: “A previously reported solid‐phase reverse transfection method for proteins (Bulkescher et al , 2017) was used for the delivery of RNPs for three endogenous genes suggesting the potential of solid‐phase reverse transfection for CRISPR/Cas9‐based gene editing, despite its low efficiency”. We apologise for any inconvenience this omission may have caused