Smoke-induced microRNA and related proteome alterations. Modulation by chemopreventive agents

Dysregulation of microRNAs (miRNAs) has important consequences on gene and protein expression since a single miRNA targets a number of genes simultaneously. This article provides a review of published data and ongoing studies regarding the effects of cigarette smoke (CS), either mainstream (MCS) or environmental (ECS), on the expression of miRNAs and related proteins. The results generated in mice, rats, and humans provided evidence that exposure to CS results in an intense dysregulation of miRNA expression in the respiratory tract, which is mainly oriented in the sense of downregulation. In parallel, there was an upregulation of proteins targeted by the downregulated miRNAs. These trends reflect an attempt to defend the respiratory tract by means of antioxidant mechanisms, detoxification of carcinogens, DNA repair, anti-inflammatory pathways, apoptosis, etc. However, a long-lasting exposure to CS causes irreversible miRNA alterations that activate carcinogenic mechanisms, such as modulation of oncogenes and oncosuppressor genes, cell proliferation, recruitment of undifferentiated stem cells, inflammation, inhibition of intercellular communications, angiogenesis, invasion, and metastasis. The miRNA alterations induced by CS in the lung of mice and rats are similar to those observed in the human respiratory tract. Since a number of miRNAs that are modulated by CS and/or chemopreventive agents are subjected to single nucleotide polymorphisms in humans, they can be evaluated according to toxicogenomic/pharmacogenomics approaches. A variety of cancer chemopreventive agents tested in our laboratory modulated both baseline and CS-related miRNA and proteome alterations, thus contributing to evaluate both safety and efficacy of dietary and pharmacological agents.     

Morbidity of open retroperitoneal lymph node dissection for testicular cancer: contemporary perioperative data

Study Type – Therapy (prospective cohort)
Level of Evidence 2b

OBJECTIVE

To review differences between primary retroperitoneal lymph node dissection (P‐RPLND) and RPLND after chemotherapy (PC‐RPLND) in a contemporary series of patients with testicular cancer, to validate the proposed low morbidity.

PATIENTS AND METHODS

Patients who had undergone RPLND at our institution in 2001–2008 were identified and their clinical charts reviewed; in all, 190 were identified and perioperative data obtained.

RESULTS

Of the 190 patients who had RPLND, 98 (52%) and 92 (48%) had P‐ and PC‐RPLND, respectively. Histology of the orchidectomy specimen consisted of embryonal carcinoma in 146 (76%) patients, also including lymphovascular invasion in 83 (44%). The mean (range) operative duration was 206 (110–475) min and the mean blood loss was 294 (50–7000) mL. The median hospital stay was 4 days. Mean blood loss, operative duration and hospital stay were significantly less for the P‐RPLND than for PC‐RPLND groups (P < 0.05). There were 18 (9%) perioperative complications in all. There were no deaths in either group.

CONCLUSIONS

The short‐term morbidity of open RPLND is acceptable, and open RPLND is safe and effective at select tertiary centres. When compared with historical data, the present contemporary series shows that the operative duration, blood loss and hospital stay have improved, with few complications. These contemporary data should be considered when comparing laparoscopic with open RPLND.     

Benzodiazepines in Miami-Dade County, Florida driving under the influence (DUI) cases (1995-1998) with emphasis on Rohypnol: GC-MS confirmation, patterns of use, psychomotor impairment, and results of Florida legislation.

Benzodiazepines are central nervous system depressant drugs often detected in biological samples from driving under the influence (DUI) offenders. They are associated with marked psychomotor impairment and represent up to 20% of all Miami-Dade County, Florida DUI urine samples analyzed in our laboratory annually. Flunitrazepam emerged in the mid-1990s as an illegal drug in the U.S. that was predominantly abused recreationally and associated with sexual assaults. Immunoassays for benzodiazepines do not discriminate between different benzodiazepines, and certain metabolites, such as 7-aminoflunitrazepam, react poorly with immunoassay reagents. A simple and sensitive method for the detection and quantitation of major benzodiazepines and metabolites by gas chromatography with mass selective detection is presented. This method was used to confirm benzodiazepines in general and flunitrazepam in particular. Data collected over a three-and-a-half-year period are summarized. Whereas flunitrazepam was present in up to 10% of DUI cases in 1995 and 1996 and had fast become the most frequently encountered benzodiazepine in Miami-Dade County DUI-related urine samples, a dramatic drop in case numbers followed the legal reclassification of the drug as a Schedule I substance in Florida in February 1997. Flunitrazepam was often used alone or in combination with cannabis and cocaine. A recent rise in clonazepam cases coincides with the decrease in flunitrazepam confirmation and may indicate a new trend in the abuse of benzodiazepines in South Florida.     

Swallow segmentation with artificial neural networks and multi-sensor fusion

Swallow segmentation is a critical precursory step to the analysis of swallowing signal characteristics. In an effort to automatically segment swallows, we investigated artificial neural networks (ANN) with information from cervical dual-axis accelerometry, submental MMG, and nasal airflow. Our objectives were (1) to investigate the relationship between segmentation performance and the number of signal sources and (2) to identify the signals or signal combinations most useful for swallow segmentation. Signals were acquired from 17 healthy adults in both discrete and continuous swallowing tasks using five stimuli. Training and test feature vectors were constructed with variances from single or multiple signals, estimated within 200 ms moving windows with 50% overlap. Corresponding binary target labels (swallow or non-swallow) were derived by manual segmentation. A separate 3-layer ANN was trained for each participant–signal combination, and all possible signal combinations were investigated. As more signal sources were included, segmentation performance improved in terms of sensitivity, specificity, accuracy, and adjusted accuracy. The combination of all four signal sources achieved the highest mean accuracy and adjusted accuracy of 88.5% and 89.6%, respectively. A–P accelerometry proved to be the most discriminatory source, while the inclusion of MMG or nasal airflow resulted in the least performance improvement. These findings suggest that an ANN, multi-sensor fusion approach to segmentation is worthy of further investigation in swallowing studies.     

Cement mantle defects and the role of distal femoral centralising devices

We performed an in vitro study to examine the effect of distal femoral centralising devices on the cement mantle after introduction of a tapered femoral prosthesis (Exeter no2 44 mm offset stem). This was assessed in relation to the timing of insertion (early, middle and late) and three different cement products (CMW 1, Simplex and Palamed). Forty-seven identical sawbone^® femora model 1130 were examined after extraction of the stem. Each cement brand was divided into three groups (early, middle and late insertion times). A fourth group was added as a control, without a centraliser. Each of the femora was assessed using a 30° endoscope combined with VHS video analysis and 1 cm axial sectioning studies to examine the integrity of the cement mantle. The results were analysed statistically using the ANOVA method. These show that early insertion is important in preventing major cement mantle defects (P < 0.5). The addition of a centraliser to the stem and insertion in the late phase led to significantly greater defects in the cement mantle (P < 0.0001). This was independent of the cement type used. We conclude that there is a relationship between the late insertion of the femoral component with a distal centraliser and large cement mantle defects. We recommend insertion of the stem in the early phase of cement curing if a centraliser is used or removal of the centraliser if this stage has passed.