Ethanol alters opioid regulation of Ca(2+) influx through L-type Ca(2+) channels in PC12 cells

Background: Studies at the behavioral and synaptic level show that effects of ethanol on the central nervous system can involve the opioid signaling system. These interactions may alter the function of a common downstream target. In this study, we examined Ca²⁺ channel function as a potential downstream target of interactions between ethanol and μ or κ opioid receptor signaling. Methods: The studies were carried out in a model system, undifferentiated PC12 cells transfected with μ or κ opioid receptors. The PC12 cells express L‐type Ca²⁺ channels, which were activated by K⁺ depolarization. Ca²⁺ imaging was used to measure relative Ca²⁺ flux during K⁺ depolarization and the modulation of Ca²⁺ flux by opioids and ethanol. Results: Ethanol, μ receptor activation, and κ receptor activation all reduced the amplitude of the Ca²⁺ signal produced by K⁺ depolarization. Pretreatment with ethanol or combined treatment with ethanol and μ or κ receptor agonists caused a reduction in the amplitude of the Ca²⁺ signal that was comparable to or smaller than that observed for the individual drugs alone, indicating an interaction by the drugs at a downstream target (or targets) that limited the modulation of Ca²⁺ flux through L‐type Ca²⁺ channels. Conclusions: These studies provide evidence for a cellular mechanism that could play an important role in ethanol regulation of synaptic transmission and behavior through interactions with the opioid signaling.     

Association of frontal QRS-T angle--age risk score on admission electrocardiogram with mortality in patients admitted with an acute coronary syndrome

Risk assessment is central to the management of acute coronary syndromes. Often, however, assessment is not complete until the troponin concentration is available. Using 2 multicenter prospective observational studies (Evaluation of Methods and Management of Acute Coronary Events [EMMACE] 2, test cohort, 1,843 patients; and EMMACE-1, validation cohort, 550 patients) of unselected patients with acute coronary syndromes, a point-of-admission risk stratification tool using frontal QRS-T angle derived from automated measurements and age for the prediction of 30-day and 2-year mortality was evaluated. Two-year mortality was lowest in patients with frontal QRS-T angles <38° and highest in patients with frontal QRS-T angles >104° (44.7% vs 14.8%, p <0.001). Increasing frontal QRS-T angle-age risk (FAAR) scores were associated with increasing 30-day and 2-year mortality (for 2-year mortality, score 0 = 3.7%, score 4 = 57%; p <0.001). The FAAR score was a good discriminator of mortality (C statistics 0.74 [95% confidence interval 0.71 to 0.78] at 30 days and 0.77 [95% confidence interval 0.75 to 0.79] at 2 years), maintained its performance in the EMMACE-1 cohort at 30 days (C statistics 0.76 (95% confidence interval 0.71 to 0.8] at 30 days and 0.79 (95% confidence interval 0.75 to 0.83] at 2 years), in men and women, in ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction, and compared favorably with the Global Registry of Acute Coronary Events (GRACE) score. The integrated discrimination improvement (age to FAAR score at 30 days and at 2 years in EMMACE-1 and EMMACE-2) was p <0.001. In conclusion, the FAAR score is a point-of-admission risk tool that predicts 30-day and 2-year mortality from 2 variables across a spectrum of patients with acute coronary syndromes. It does not require the results of biomarker assays or rely on the subjective interpretation of electrocardiograms.     

Landscape-level spatial patterns of West Nile virus risk in the northern Great Plains

Understanding the landscape-level determinants of West Nile virus (WNV) can aid in mapping high-risk areas and enhance disease control and prevention efforts. This study analyzed the spatial patterns of human WNV cases in three areas in South Dakota during 2003-2007 and investigated the influences of land cover, hydrology, soils, irrigation, and elevation by using case-control models. Land cover, hydrology, soils, and elevation all influenced WNV risk, although the main drivers were different in each study area. Risk for WNV was generally higher in areas with rural land cover than in developed areas, and higher close to wetlands or soils with a high ponding frequency. In western South Dakota, WNV risk also decreased with increasing elevation and was higher in forested areas. Our results showed that the spatial patterns of human WNV risk were associated with landscape-level features that likely reflect variability in mosquito ecology, avian host communities, and human activity.     

Bone mineral density measurements performed by cone-beam computed tomography in the bisphosphonate-related osteonecrosis-affected jaw

Objectives

The aims of this study were to determine the bone mineral density (BMD) in bisphosphonate-related osteonecrosis of the jaw (BRONJ) by cone-beam computed tomography (CBCT) measurements and to correlate these measurements with the current stages recommended by the American Association of Oral and Maxillofacial Surgeons (AAOMS).

Methods

Bone mineral density measurements of various areas in 24 bisphosphonate-related osteonecrosis (BRON) jaws were evaluated by CBCT. Another 24 age- and sex-matched patients without any bone pathologies served as the control group. Data acquisition was highly standardized to ensure maximum reliability in the comparisons of BMD measurements by CBCT.

Results

Compared with the control group, the bisphosphonate patients had significantly higher (p????0.01) BMDs in the non-affected jaw areas ipsilateral and contralateral to the BRON within the maxilla and mandible. The highest BMDs within the BRON jaws were observed in the BRON-adjacent areas relative to the non-affected ipsilateral and contralateral areas. Regarding the correlation with the AAOMS stages, the BMDs of the evaluated areas of BRONJ showed no significant differences (p????0.05) between the stages.

Conclusions

Bisphosphonate-related bone pathologies can be detected by CBCT and are associated with increased BMDs, not only in clinically obvious BRONJ areas, but also in clinically unapparent areas, suggesting a subclinical general osteosclerosis of the jaw. The data transferability to other CBCT devices needs to be further elucidated and compared with multislice CT.     

Sequential second free fibula flap for the reconstruction of metachronous osteoradionecrosis of the mandible

Osteoradionecrosis (ORN) of the mandible is a potentially catastrophic complication of external beam radiation therapy for head and neck malignancies. A 55-year-old man treated with chemoradiation for base-of-tongue cancer presented with a necrotic left mandibular body and underwent left mandibulectomy with right free fibula osteocutaneous flap reconstruction. Two and a half years later, he presented with right mandibular body ORN and underwent a second mandibular resection and subsequent reconstruction with a left fibula osteocutaneous free flap fixed in the midline to the previously placed contralateral fibula. He recovered well from all procedures. To the best of our knowledge, we report the first case of a patient with metachronous ORN of the mandible requiring resection and subsequent reconstruction with sequential free fibula flaps. Even in the presence of prior microvascular reconstructions, patients can successfully undergo additional reconstructive procedures to restore their function, appearance, and quality of life.     

Innovation in anterior mandibular alveolar distraction osteogenesis: Introduction of a new bone-borne distraction device and first clinical results

Segmental distraction osteogenesis of the anterior mandibular alveolar process (frontblock) is a sufficient method to avoid extractions in patients with dental crowding and to decompensate retroalveolism. Up to now dental-borne devices were used, but limitate the indications for front-block distraction.A new bone-borne distraction device for mandibular alveolar front-block movement is introduced in this study. The distractor allows sufficient segmental transport without loading on the teeth. Clinical evaluations of 7 patients have been performed including the feasibility and predictability of the distraction, postoperative pain and patients’ discomfort. The results indicate that this technique is a promising strategy in the correction of dental crowding, correcting the curve of Spee and to decompensate mandibular retroalveolism even in patients with impaired periodontal health and a thin mandibular symphysis.