Risk of recurrence in major central nervous system malformations between 1976 and 2005

OBJECTIVE: The goal of the current publication is to review isolated central nervous system malformations (CSMs) using a database in excess of 75 000 cases, with special regard to the risk of recurrence of these malformations alone or in combination. METHODS: In the period between 1 January 1976 and 31 December 2005, among the 75 320 documented cases, consultations were requested due to earlier isolated CSMs in the patients' histories in 3030 cases (4.2%). Processing the data we only considered disorders of genetic origin, and that was why we excluded the cases due to intrauterine infection. Monogenically inherited malformations were also excluded from the analysis. The diagnosis of the malformations was based on the prenatal diagnosis of ultrasonography as well as the findings of the foetopathological examination. RESULTS: In 65% of the cases, the couples sought counselling because of malformation in a previous pregnancy. In these cases, the risk of recurrence was thought to be 5.2%, while in the case of two affected children this figure stood at 21.9%. Analysing the values for the risk of recurrence in 5-year periods, neural tube defects (NTDs) (particularly anencephaly and spina bifida) showed a detectable decrease, which could be attributed to a growing use of folic acid supplementation around the time of conception and during pregnancy. CONCLUSION: There is a clear decrease of risk of recurrence of NTDs, while in the case of the other CSMs in this study, there is no noteworthy chronological change in their risk of recurrence.     

Predictive Value of Sonographic Features in Preoperative Evaluation of Malignant Thyroid Nodules in a Multinodular Goiter

BACKGROUND: The primary goal of ultrasonography (US) in the evaluation of a thyroid nodule is to determine its malignancy, although the diagnosis of a malignant nodule on the basis of US alone is nearly impossible. The aim of this prospective study was to evaluate the predictive value of sonographic features in the preoperative diagnosis of malignant thyroid nodules, and to determine the important features of sonography. METHODS: This prospective study included 550 consecutive patients with , thyroid nodules. Nodules were divided into two groups on the basis of pathological diagnosis: group 1 consisted of 1,633 nodules with a benign pathology, and group 2 consisted of 293 nodules with a malignant pathology. RESULTS: Microcalcifications, blurred nodular margins, and solid and hypoechoic appearance were more common in malignant nodules compared to benign nodules (89.1% versus 5%; 64.5% versus 4.7%; 81.6% versus 30.6% ; and 62.5% versus 43.1%, respectively; p < 0.001). There was a positive correlation between the detection of malignant thyroid nodules and microcalcification (rs = 0.791, p = 0.0001), blurred nodular margin (rs = 0.625, p = 0.0001), solid appearance (rs = 0.376, p = 0.0001), and hypoechoic appearance (rs = 0.141, p = 0.0001). Microcalcifications, blurred nodular margins, and solid and hypoechoic appearance were independent determinants of malignancy upon US examination of thyroid nodules (OR: 159, OR: 37, OR: 9.9, and OR: 2.2, respectively). CONCLUSION: Although we did not identify a single feature indicative of malignancy in the sonographic examination of nodules, microcalcification and blurred margin were the strongest correlates for malignancy.     

Analgesic effect of a low-level laser therapy (830 nm) in early orthodontic treatment

The aim of this study was to evaluate the pain sensation that orthodontic patients experience when elastic separators are placed between molars and premolars and to determine the degree of analgesic efficacy of low-level laser therapy (LLLT) compared to a placebo treatment. The study was conducted with 20 volunteers who were fitted with elastic separators between the maxillary molars and premolars. One quadrant was randomly chosen to be irradiated with an 830-nm laser, 100 mW, beam diameter of 7 mm, 250 mW/cm² applied for 20 s per point (5 J/cm²). Three points were irradiated in the buccal face and three were irradiated in the palate. The same procedure was applied in the contralateral quadrant with a placebo light. A visual analogue scale was used to assess pain 5 min, 6 h, 24 h, 48 h, and 72 h after placement of the separators. Maximum pain occurred 6–24 h after placement of the elastic separators. Pain intensity was significantly lower in the laser-treated quadrant (mean, 7.7 mm) than in the placebo-treated quadrant (mean, 14.14 mm; p?=?0.0001). LLLT at these parameters can reduce pain in patients following placement of orthodontic rubber separators.     

A glutamate residue at the C terminus regulates activity of inward rectifier K+ channels: implication for Andersen's syndrome

G protein-coupled inward rectifiers (GIRKs) are activated directly by G protein betagamma subunits, whereas classical inward rectifiers (IRKs) are constitutively active. We found that a glutamate residue of GIRK2 (E315), located on a hydrophobic domain of the C terminus, is crucial for the channel activation. This glutamate (or aspartate) residue is conserved in all members of the Kir family. Substitution of alanine for the glutamate on GIRK1, GIRK2, and IRK2, expressed in HEK293 cells, greatly reduced the whole-cell currents. The whole-cell current of GIRK channels with a constitutively active gate, GIRK2(V188A), [Yi, B. A., Lin, Y. F., Jan, Y. N. & Jan, L. Y. (2001) Neuron 29, 657-667] was also reduced by the same glutamate mutation. Mean open time and conductance of single channels in GIRK2 and IRK2 were not affected by the mutation, indicating that the reduced whole-cell current resulted from a lowered probability of channel activation. The mutated GIRK and IRK showed normal trafficking to the cell membrane. The mutated GIRK2 retained the ability to interact with G protein betagamma subunits, and it showed almost the same inwardly rectifying property as the wild type. The mutated GIRK1 and GIRK2 retained ion selectivity to K(+) ions. This glutamate residue corresponds to one of the residues causing Andersen's syndrome [Plaster, N. M., Tawil, R., Tristani-Firouzi, M., Canun, S., Bendahhou, S., Tsunoda, A., Donaldson, M. R., Iannaccone, S. T., Brunt, E., Barohn, R., et al. (2001) Cell 105, 511-519]. Our interpretation is that this region of the glutamate residue is crucial in relaying the activating message from the ligand sensor region to the gate.     

Stability of immune serum globulin during storage: effects of prior heating

Summary. Samples of Immune Serum Globulin (Human) [ISG] stored for 0–11 years at 5°C were examined by ultracentrifugation, starch gel electrophoresis, and solubility in trichloroacetic acid. The extent of proteolytic degradation was dependent on the manufacturing process (salt or ethanol precipitation) and the source (venous, placental, or mixed). Incubation of ISG with added plasmin at temperatures from -23°C to 50°C showed that maximum degradation to 3.5 S material occurred at 24°C, relatively little occurred at 45°C, and none occurred at -23°C or 50°C. Placental ISG was stored, without added plasmin, for up to 2 years, and the following observations were made: considerably more proteolysis took place at 24°C than at 5°C; heating at 45°C or 50°C prior to storage at 24°C markedly reduced the extent of degradation; and the magnitude of this reduction was the same for samples heated at 45°C for 36 h, 48 h, or 72 h, or at 50°C for 72 h. Heating at 45°C produced minimal changes in the electrophoretic or anticomplementary characteristics of ISG but did result in a marked decrease in the amount of 10 S material present.     

Cell‐free microRNAs as diagnostic,prognostic, and predictive biomarkers for lung cancer

Lung cancer is the most common cancer worldwide, accounting for over 1.37 million deaths annually. The clinical outcome and management of lung cancer patients could be substantially improved by the implementation of non‐invasive biomarker assays for the early detection, prognosis as well as prediction and monitoring of treatment response. MicroRNAs (miRNAs) have been implicated in the regulation of virtually all signaling circuits within a cell and their dysregulation has been shown to play an essential role in the development and progression of cancer. Recently, miRNAs were found to be released into the circulation and to exist there in a remarkably stable form. Furthermore, various cancers were shown to leave specific miRNA fingerprints in the blood of patients suggesting that cell‐free miRNAs could serve as non‐invasive biomarkers for the detection or monitoring of cancer and putative therapeutic targets. Since that, a considerable effort has been devoted to decode the information carried by circulating miRNAs. In the current review, we give an insight into the mechanisms of miRNA release into the bloodstream, their putative functional significance and systematically review the studies focused on the identification of cell‐free miRNAs with the diagnostic, prognostic, and predictive significance in lung cancer and discuss their potential clinical utility. © 2012 Wiley Periodicals, Inc.     

Hypothyroidism: age-related influence on cardiovascular nitric oxide system in rats

This study investigates whether changes in nitric oxide (NO) production participate in the cardiovascular manifestations of hypothyroidism and whether these changes are age-related. Sprague-Dawley rats aged 2 and 18 months old were treated with 0.02% methimazole (wt/vol) during 28 days. Left ventricular function was evaluated by echocardiography. Measurements of arterial blood pressure, heart rate, nitric oxide synthase (NOS) activity and NOS/caveolin-1 and -3 protein levels were performed. Hypothyroidism enhanced the age-related changes in heart function. Hypothyroid state decreased atrial NOS activity in both young and adult rats, associated with a reduction in protein levels of the three NOS isoforms in young animals and increased caveolin (cav) 1 expression in adult rats. Ventricle and aorta NOS activity increased in young and adult hypothyroid animals. In ventricle, changes in NOS activity were accompanied by an increase in inducible NOS isoform in young rats and by an increase in caveolins expression in adult rats. Greater aorta NOS activity level in young and in adult Hypo rats would derive from the inducible and the endothelial NOS isoform, respectively. Thyroid hormones would be one of the factors involved in the modulation of cardiovascular NO production and caveolin-1 and -3 tissue-specific abundance, regardless of age. Hypothyroidism appears to contribute in a differential way to aging-induced changes in the myocardium and aorta tissues. Low thyroid hormones levels would enhance the aging effect on the heart. Age-related changes in NO production participate in the cardiovascular manifestations of hypothyroidism.