Assessment of MUSASHI 1 and MUSASHI 2 expression in spermatozoa and testicular tissue

MUSASHI (MSI) family plays the main role in the spermatogenesis process. The purpose of this study was the assessment of sperm MSI1 and MSI2, and sperm functional tests in infertile men (n = 30) with varicocele and fertile men (n = 30). Furthermore, MSI1 and MSI2 proteins were assessed in testicular tissue of azoospermic men (n = 9) as well as epididymal spermatozoa and testis of mice. Expression of MSI1 and MSI2 was assessed at RNA and protein levels in human spermatozoa. Sperm concentration and motility were significantly lower, while abnormal sperm morphology, lipid peroxidation, DNA fragmentation and protamine deficiency were significantly higher in men with varicocele compared to fertile individuals. Any significant difference was not observed in the expression of MSI1 and MSI2 mRNA between the two groups. Unlike MSI1 protein that was not detectable in humans, the relative expression of MSI2 protein was similar in varicocele and fertile individuals. The expression level of both Msi1 and Msi2 proteins was also observable in mouse spermatozoa. No significant relationship was observed between sperm functional parameters with expression of these genes. The data of this study demonstrated that although MSI1 and MSI2 play important roles during spermatogenesis, their relative expression in spermatozoa was not affected by varicocele.     

Automated Continuous Acute Kidney Injury Prediction and Surveillance: A Random Forest Model

ObjectiveTo develop and validate a prediction model of acute kidney injury (AKI) of any severity that could be used for AKI surveillance and management to improve clinical outcomes.Patients and MethodsThis retrospective cohort study was conducted in medical, surgical, and mixed intensive care units (ICUs) at Mayo Clinic in Rochester, Minnesota, including adult (≥18 years of age) ICU-unique patients admitted between October 1, 2004, and April 30, 2011. Our primary objective was prediction of AKI using extant clinical data following ICU admission. We used random forest classification to provide continuous AKI risk score.ResultsWe included 4572 and 1958 patients in the training and validation mutually exclusive cohorts, respectively. Acute kidney injury occurred in 1355 patients (30%) in the training cohort and 580 (30%) in the validation cohort. We incorporated known AKI risk factors and routinely measured vital characteristics and laboratory results. The model was run throughout ICU admission every 15 minutes and achieved an area under the receiver operating characteristic curve of 0.88 on validation. It was 92% sensitive and 68% specific and detected 30% of AKI cases at least 6 hours before the criterion standard time (AKI stages 1-3). For discrimination of AKI stages 2 to 3, the model had 91% sensitivity, 71% specificity, and 53% detection of AKI cases at least 6 hours before AKI onset.ConclusionWe developed and validated an AKI prediction model using random forest for continuous monitoring of ICU patients. This model could be used to identify high-risk patients for preventive measures or identifying patients of prospective interventional trials.     

Surgical treatment of cerebellopontine angle meningiomas in elderly patients

Summary Background. The aim of this study is to assess the morbidity and mortality of meningioma surgery in patients over 70 years of age harbouring a tumour at the cerebellopontine angle as one representative location of the posterior fossa in comparison with a matched group of young patients.Method. A retrospective analysis based on clinical charts, surgical records, histological records, imaging studies and follow up records was conducted to select patients over 70 years who underwent surgery for cerebellopontine angle meningiomas. Tumours with comparable size and location were matched with the younger group.Findings. There were 421 meningiomas located in the cerebellopontine angle, 21 patients were older than 70 years (range 70–84). Median Karnofsky-Index at presentation was 80 (50–90), 16 patients had a physical status grading ASA 2 and 5 patients ASA 3. The average length of hospital stay was 22 days (7–99 days). The postoperative median Karnofsky score at time of discharge was 80 (50–90). The most common medical complication was postoperative pneumonia in 4 patients, among them 3 patients had lower cranial nerve disturbances postoperatively. There were 56 younger patients (mean age 52.4 years; range 24.5–69.75 years) with corresponding tumour size and location. Pre-op Karnofsky score was 80 (70–90), 53 patients were graded as ASA 2 and 3 patients as ASA 3. Length of hospital stay was 13.6 days (8–32 days). Post-op Karnofsky score was 80 (50–90). Among 5 patients with postoperative lower cranial nerve disturbances no patient had pneumonia postoperatively. There was no peri-operative mortality in either group.Conclusions. With modern neurosurgical techniques and neuro-anesthesia elderly patients with CPA meningiomas can be operated on with acceptable low morbidity and good neurological outcome but recovery from surgery lasts longer compared to younger patients. However, postoperative lower cranial nerve deficits in elderly patients may not be well tolerated compared with younger patients.     

Time-intensity trading in bilateral congenital aural atresia patients

In an effort to examine the rules by which information of bilaterally applied bone-conducted signals arising from interaural time differences (ITD) and interaural intensity differences (IID) is combined, data were measured for continuous 500 Hz narrow band noise at 65-70 dB HL in 11 patients with bilateral congenital aural atresia. Time-intensity trading functions were obtained by shifting the sound image towards one side using ITD, and shifting back to a centered sound image by varying the IID in the same ear (auditory midline task). ITD values were varied from -600 to +600 micros at 200 micros steps, where negative values indicate delays to the right ear. The results indicate that time-intensity trading is present in patients with bilateral aural atresia. The gross response properties of time-intensity trading in response to bone-conducted signals were comparable in patients with bilateral aural atresia and normal-hearing subjects, though there was a larger inter-subject variability and higher discrimination thresholds across IIDs in the atresia group. These results suggest that the mature auditory brainstem has a potential to employ binaural cues later in life, although to a restricted degree. A binaural fitting of a bone-conducted hearing aid might optimize binaural hearing and improve sound lateralization, and we recommend now systematically bilateral fitting in aural atresia patients.     

Involvement of the PI 3-kinase signaling pathway in progression of colon adenocarcinoma

The phosphoinositide 3-kinase (PI 3-kinase) signaling pathway has been shown to play a pivotal role in intracellular signal transduction pathways involved in cell growth, cellular transformation and tumorigenesis. Analysis of several colon adenocarcinoma cell lines indicates that the PI 3-kinase signaling pathway is up-regulated in colon cancers. In particular, the protein levels and phosphorylation status of Akt and p70 S6 kinase are up-regulated in colon adenocarcinoma cell lines. More significantly, we have demonstrated for the first time that the phosphorylation of FKHR, a downstream target of Akt, is increased in these cell lines. Intriguingly, phosphorylation of three components of the PI 3-kinase signaling pathway, namely Akt, p70 S6 kinase and FKHR, are in direct correlation with the degree of tumorigenic potential of the colon cell lines tested. No differences in the protein levels of the two subunits of PI 3-kinase, p85 and p110alpha, and PTEN were noted. Real-time quantitative PCR indicated an increase in levels of Akt message only, and not of the other signaling pathway components. Inhibition of the PI 3-kinase with wortmannin decreased the anchorage-independent growth of colon cells in a soft agar assay. Hence, the components of the PI 3-kinase signaling pathway could serve as potential candidates for drug development in treatment of colon cancer.     

Effect of Continuous Venovenous Hemofiltration Dose on Achievement of Adequate Vancomycin Trough Concentrations

The vancomycin dose necessary for the achievement of target serum trough concentrations during continuous venovenous hemofiltration (CVVH) remains to be elucidated. This was a retrospective cohort study of critically ill adults at a tertiary medical center on concurrent CVVH and vancomycin between 2006 and 2010 with a steady-state vancomycin trough concentration. The 87 included patients were grouped according to low (≤30 ml/kg/h; n = 10) or high (>30 ml/kg/h; n = 77) CVVH hemofiltration rate (HFR) for analysis. Vancomycin goal trough achievement occurred in only 32 (37%) patients. The primary endpoint of trough attainment significantly differed between HFR subgroups: 90% versus 30% in low- and high-HFR individuals, respectively (P < 0.001). Patients with subtherapeutic trough concentrations had a median (interquartile range) HFR of 40 ml/kg/h (range, 37 to 47 ml/kg/h) compared to 36 ml/kg/h (range, 30 to 39 ml/kg/h) in those who achieved the trough goal. Irrespective of goal trough, an inverse correlation existed between HFR and serum vancomycin concentration (r = −0.423; P < 0.001). In the subgroup of 14 methicillin-resistant Staphylococcus aureus (MRSA) patients, trough achievement was similar to the aggregate cohort (36%). Mortality at 28 days was unrelated to trough achievement in both the overall sample (P = 0.516) and in culture-positive MRSA patients (P = 0.396). Critically ill patients undergoing CVVH therapy may experience clinically significant reductions in goal vancomycin troughs. The results of the present study justify prospective evaluations in this population to determine the optimal vancomycin dosing strategy for attainment of goal trough concentrations.     

Vestibular evoked myogenic potentials evoked by multichannel cochlear implant - influence of C levels

CONCLUSIONS: This study showed that vestibular evoked myogenic potentials (VEMPs) evoked by cochlear implant (CI), could be related to the comfortable level (C level), particularly in the channels that are closer to the apical turn of the cochlea. OBJECTIVE: The purpose of this study was to investigate the correlation between VEMPs and C level of each channel. SUBJECTS AND METHODS: We investigated 24 children who underwent cochlear implantation. VEMPs were recorded from the operated ears with the CI switched 'off' or 'on'. To investigate the correlation between VEMPs and C level, we selected 13 patients with Nucleus 24 (SPrint), and divided them into group A (normal VEMPs) and B (absence of VEMPs). In these children, all the 22 electrodes were active, and were mapped in the same frequency range for each channel. RESULTS: Twenty children (83%) showed no VEMPs with the CI 'off'. Among them, 10 elicited VEMPs with the CI 'on', but the other 10 did not. In all channels, the mean C levels of CI were higher in group A than in group B. The p values in channels 1-12 were >0.10, in channels 13-16 were 0.06-0.09, and in channels 17-22 were 0.05-0.06, which were lower but not statistically significant.