[Importance of radiographic study in diagnosis of temporomandibular pathology].
The X-ray survey is an important complement in the diagnosis of the temporomandibular pathology, anyone be the modality of it. The complexity of the articular structure origins difficulties in order to obtain an objective analysis of them, and the presence of radio-transparent articular elements is another factor attempting against the radiological study. This X-ray survey must be realized by experimented professional in an multidisciplinary equipment in the temporomandibular management.


De novo protein synthesis in isolated axons of identified neurons.
Neurons are highly polarized cells that contain a wealth of cytoplasmic and membrane proteins required for neurotransmission, synapse formation and various forms of neuronal plasticity. Typically, these proteins are differentially distributed over somatic, dendritic and axonal compartments. Until recently, it was believed that all proteins destined for various neuronal sites were synthesized exclusively in the somata and were subsequently targeted to appropriate extrasomal compartments. The discovery of various messenger RNA molecules in both dendrites and axons is suggestive of de novo protein synthesis in extrasomatic regions. The latter process has been demonstrated in few neuronal svrstems, but direct proof for the axonal transcription of a specific protein from a given messenger RNA is still lacking. This lack of fundamental knowledge in the field of cellular and molecular neurobiology is due primarily to both anatomical and experimental difficulties encountered in most animal preparations studied thus far. In this study we developed a neuronal experimental system comprising of individually identified neurons and their isolated axons from the mollusc Lymnaea stagnalis. We injected a foreign messenger RNA encoding a peptide precursor into the isolated axons of cultured neurons; and utilizing cellular, molecular and immunocytochemical techniques, we provide direct evidence for specific protein synthesis in isolated axons. The Lymnaea model provides us with an opportunity to examine the role and specificity of de novo protein synthesis in the extrasomal regions.


Carbohydrate-binding proteins from the sieve-tube sap of Robinia pseudoacacia L.
Evidence is provided for the occurrence of lectins (phytohemagglutinins) in the sieve-tube sap of Robinia pseudoacacia L. The most potent sugars found to inhibit the complex formation of the soluble protein with rabbit erythrocytes were N-acetyl-galactosamine and glycosides containing galactose. Sucrose and inositol had weaker effects. The extract of the membraneous material present in the sieve-tube sap also contains lectins, but the sugar specifity is different.


Adsorption of cations onto the surfaces of silver nanoparticles.
The effects of cations on the absorption spectra of silver sols have been investigated by the UV-vis spectrometry and TEM. Experiments showed that injection of certain amounts of transition metal cations into silver sols resulted not only in the aggregation of silver nanoparticles but also in the appearance of a new band centered near 510 nm in the absorption spectra of silver sols. However, the new band was not observed in the presence of alkaline earth metal cations or the Mv2+ cations. The peak position of the new band depends on the nature as well as the concentration of metal cations used. Comparing the peak positions of the new bands, it was found that the new band induced by the injection of Cr3+ was red-shifted with respect to those induced by Cu2+, Zn2+, or the Cd2+ cations. It is reasonable that this band near 510 nm should be attributed to the coeffects of the adsorption of metal cations onto the surfaces of silver nanoparticles and the aggregation of silver nanoparticles.


Incontinence in the frail elderly: report from the 4th International Consultation on Incontinence.
To summarize current knowledge on the etiology, assessment, and management of urinary incontinence (UI) in frail older persons. "Frail" here indicates a person with a clinical phenotype combining impaired physical activity, mobility, muscle strength, cognition, nutrition, and endurance, associated with being homebound or in care institutions and a high risk of intercurrent disease, disability, and death. Revision of 3rd ICI report using systematic review covering years 2004-2008. We focus on the etiologic, management, and treatment implications of the key concept that UI in frail persons constitutes a syndromic model with multiple interacting risk factors, including age-related physiologic changes, comorbidity, and the common pathways between them. We present new findings with evidence summaries based on all previous data, and an evidence-based algorithm for evaluation and management of UI in frail elderly. We also present new evidence and summarize the data on etiology and management of nocturia and urinary retention in frail elderly. Despite the overwhelming burden of UI among this population, there remains a continuing paucity of new clinical trials in frail elderly, limiting evidence for the effectiveness of the full range of UI therapy. Future research is needed on current UI treatments (especially models of care delivery, and pharmacologic and surgical therapies), novel management approaches, and the etiologic mechanisms and pathways of the syndromic model.


Delipidating in vitro-produced bovine zygotes: effect on further development and consequences for freezability.
To study the effect of partial removal of intracytoplasmatic lipids from bovine zygotes on their in vitro and in vivo survival, presumptive zygotes were delipidated by micromanipulation and cocultured with Vero cells in B2+10% FCS. Blastocyst rates of delipidated (n=960), sham (centrifuged but not delipidated, n=830) and control embryos (n=950) were 42.1, 42.3 and 39.9% respectively (P > 0.05). Day 7 blastocysts derived from delipidated zygotes had a mean of 123.9 +/-45.6 nuclei compared to 137.5+/-32.9 for control blastocysts (P > 0.05). The full-term development of delipidated blastocysts after single transfer to recipients was similar to that of control IVF blastocysts (41.2% vs 45.4% respectively). To assess the effect of delipidation on the embryo tolerance to freezing/thawing, delipidated (n=73), control (n=67) and sham (n=50) Day 7 blastocysts were frozen in 1.36 M glycerol + 0.25 M sucrose in PBS. After thawing, embryos were cocultured for 72 h with Vero cells in B2+10% FCS. Survival rates at 24 h were not significantly different between groups. However, in the delipidated group, the survival rate after 48 h in culture was significantly higher than in the control group (56.2 vs 39.8, P < 0.02), resulting in a higher hatching rate after 3 days in culture (45.2 vs 22.4, P < 0.02). Pregnancy rates for delipidated and control frozen/thawed embryos were respectively 10.5 and 22.2% (P > 0.05). Electron microscopic observations showed much fewer lipid droplets (and smaller) in delipated blastocysts than in controls. Taken together, our data show that delipidation of one cell stage bovine embryos is compatible with their normal development to term and has a beneficial effect on their tolerance to freezing and thawing at the blastocyst stage. This procedure, however, alters the developmental potential of such blastocysts, suggesting that maternally inherited lipid stores interfere with metabolic recovery after thawing.


Effect of inter-individual blood pressure variability on the progression of atherosclerosis in carotid and coronary arteries: a post hoc analysis of the NORMALISE and PREVENT studies.
To investigate the relationship between visit-to-visit blood pressure variability (BPV) and the progression of both carotid and coronary artery disease (CAD). Data from two cardiovascular endpoint studies [Norvasc for Regression of Manifest Atherosclerotic Lesions by Intravascular Sonographic Evaluation (NORMALISE) and Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT)] were analysed separately. Systolic BPV was assessed as within-subject standard deviation of systolic BP across visits from 12-weeks onwards. Follow-up was 24 months (NORMALISE) or 36 months (PREVENT). Any association between BPV and progression of atherosclerosis was assessed using quantitative coronary angiography (QCA), intravascular ultrasound (IVUS), or B-mode ultrasound (depending on study). Patients from NORMALISE (n = 261) and PREVENT (n = 688 for QCA; n = 364 for ultrasound) were stratified within study according to median systolic BPV. No significant difference in change of minimal luminal diameter (by QCA in PREVENT) or change in percent atheroma volume or normalized total atheroma volume (by IVUS in NORMALISE) was detected for subjects with low BPV (BPV < median) compared with high BPV (BPV ≥ median), regardless of treatment. In PREVENT, a significantly greater reduction in maximum carotid intima-media thickness (IMT) (left and right common carotid artery far wall) was observed for patients with BPV < median compared with those with BPV ≥ median [least squares mean difference 0.06 (95% confidence interval 0.01, 0.11); P = 0.0271], after adjusting for treatment, carotid artery segment (left or right), baseline maximum carotid IMT, and other baseline and cardiovascular risk factors/covariates. In patients with existing CAD and well-controlled BP, visit-to-visit BPV was not associated with progression of coronary atherosclerosis; however, a significantly greater reduction in maximum carotid IMT was observed for patients with low BPV.


Alteplase use for prevention of central line occlusion in a preterm infant.
To report the use of alteplase for catheter clearance in a neonate of 27 weeks' gestation at day 50 of life. Neonatal Intensive Care Unit, Naval Medical Center. At day 50 of life, a neonate boy of 27 weeks' gestation had a clotted peripherally inserted central catheter line. He required central access to complete a 28-day course of amphotericin B. An alteplase dose of 0.3 mg/0.3 mL was instilled into the catheter, for an indwelling time of 1 hour. The initial attempt was successful, and the patient was able to finish the course of amphotericin B. When a catheter becomes occluded, the cause must be determined initially; then an appropriate treatment option can be initiated. Hydrochloric acid and ethanol are some of the pharmacologic agents available, with their use dependent on the precipitating cause of the occlusion. Thrombolytic agents, such as streptokinase and urokinase, have also been used in catheter clearance. The potential risk of anaphylactic reactions with streptokinase and the unavailability of urokinase have clinicians searching for other pharmacologic alternatives. Alteplase, a synthetic tissue plasminogen activator, has been shown to be a promising alternative agent. There are various reports of alteplase use in pediatric patients for catheter clearance, with different suggested doses ranging from 0.25 to 2 mg. To minimize the risk of bleeding events, initiation with low doses from the suggested range is recommended. Alteplase was shown to be safe and effective for clearance of an occluded central line in a preterm infant.


Metadynamics for automatic sampling of quantum property manifolds: exploration of molecular biradicality landscapes.
We present a general extension of the metadynamics allowing for an automatic sampling of quantum property manifolds (ASQPM) giving rise to functional landscapes that are analogous to the potential energy surfaces in the frame of the Born-Oppenheimer approximation. For this purpose, we employ generalized electronic collective variables to carry out biased molecular dynamics simulations in the framework of quantum chemical methods that explore the desired property manifold. We illustrate our method on the example of the "biradicality landscapes", which we explore by introducing the natural orbital occupation numbers (NOONs) as the electronic collective variable driving the dynamics. We demonstrate the applicability of the method on the simulation of p-xylylene and [8]annulene allowing to automatically extract the biradical geometries. In the case of [8]annulene the ASQPM metadynamics leads to the prediction of biradical scaffolds that can be stabilized by a suitable chemical substitution, leading to the design of novel functional molecules exhibiting biradical functionality.


Simple measurement of aneurysm residual after treatment: the SMART scale for evaluation of intracranial aneurysms treated with flow diverters.
Primary endovascular reconstruction with flow diversion represents a fundamental paradigm shift in the technique of endovascular aneurysm treatment. Unlike coil embolization, often there remains residual post-procedural filling within the aneurysm with flow diverters, the curative reconstruction presumably occurring over a period of weeks. Thus, conventional grading scales for post-procedural aneurysm occlusion and recanalization are inadequate. The aim of this paper is to propose a new angiographic grading scale that addresses this fundamentally new treatment option. A five-point grading scale describes the location of residual flow within the aneurysm in the venous phase [grade 1: patent aneurysm with diffuse inflow; grade 2: residual filling of the aneurysm dome (saccular) or wall (fusiform); grade 3: only residual neck (saccular) or only intra-aneurysmal filling with former boundaries covered (fusiform); grade 4: complete occlusion]. Grade 0 represents any aneurysm, regardless of occlusion rate with early phase, coherent inflow jet. Intra-aneurysmal flow stagnation is categorized into: (a) none, (b) capillary phase, and (c) venous phase. Prevailing parent vessel hemodynamics with in-stent stenosis (ISS) are divided into none (ISS0), mild (ISS1), moderate (ISS2), severe (ISS3), and total (ISS4) occlusion. The proposed grading scales allow assessment of the hemodynamic consequences of stent placement on endosaccular in-flow, stasis, and location of stasis as well as parent vessel hemodynamics. Further studies need to show the applicability and possible predictive value of this new grading scale on the efficacy of the stent in promoting intra-aneurysmal flow stagnation, thus creating the potential to harmonize the results of future papers. This may help to optimize treatment and future device design.


[Current concepts on prolactin physiology: molecular variants and mechanisms of action].
Prolactin is a polymorphic hormone with multiple biological functions. The versatility in the actions of prolactin depends on its structural polymorphism and perhaps on the feasibility of prolactin to be converted into different bioactive forms. In this review we attempt to summarize information concerning the synthesis, structure and mechanisms of action, including the heterogeneous nature of prolactin and its possible physiological significance in humans.


Efficacy of Deferasirox for the treatment of iron overload in Chinese thalassaemia major patients: results from a prospective, open-label, multicentre clinical trial.
To assess the efficacy and safety of deferasirox in Chinese thalassaemia major (TM) patients EPIC (Evaluation of Patients' Iron Chelation with Exjade(®)) was a large multi-national study and, notably, the first clinical trial of an iron chelator registered with the Chinese State Food and Drug Administration. Efficacy and safety of deferasirox were compared in Chinese (n = 117) and non-Chinese (n = 998) TM patients. Deferasirox was initiated at 20 mg kg(-1) day(-1), with titration increments of 5-10 mg kg(-1) day(-1), based on serum ferritin trends and safety parameters. At baseline, Chinese patients were younger than non-Chinese (mean age 6·8 versus 19·5 years), with higher median serum ferritin (4519 vs 3058 ng mL(-1)). Over 1 year, mean actual deferasirox dose was similar for Chinese and non-Chinese patients (24·6 and 24·0 mg kg(-1) day(-1), respectively); median serum ferritin did not change significantly from baseline in Chinese patients (+340 ng mL(-1), P = 0·102) and significantly decreased in non-Chinese patients (-220 ng mL(-1); P < 0·001). In the 1-year extension in Chinese patients, (mean actual deferasirox dose 33·6 mg kg(-1) day(-1)), median serum ferritin decreased (-756 ng mL(-1); P = 0·0397), with a numerically higher reduction in patients aged ≥6 to < 12 than <6 years (-982 vs -457 ng mL(-1), respectively). The safety profile of deferasirox in Chinese patients was similar to the overall population with respect to clinically-relevant findings. Age and deferasirox exposure influenced study findings, supporting the need for longer-term treatment and dose escalation to ≥30 mg kg(-1) day(-1) to achieve neutral or negative iron balance in heavily iron overloaded and younger Chinese patients.


Evaluation of late redislocation in patients who underwent open reduction and pelvic osteotomy as treament for developmental dysplasia of the hip.
The goal in the treatment of developmental dysplasia of the hip (DDH) is to achieve a stable and concentric reduction and to create a congruent relationship between the femoral head and the acetabulum. This study discusses the causes of loss of reduction in DDH patients who had a concentrically reduced hip at the time of removal of the hip spica cast and cessation of brace use and who later appeared with hip redislocation after mobilisation and ambulation. In addition, the possible interventions in such cases are also discussed. A retrospective evaluation was made of 13 patients diagnosed with DDH who developed redislocation following primary surgery. 6 of them had undergone the 1st surgery in our department between 2008 and 2016 and 7 had udergone surgery in another centre. For comparison reasons a 2nd group was formed of 13 demographically and clinically matched patients who had no loss of reduction. The groups were compared in terms of acetabular index, pelvic length, pelvic width, abduction degree of plaster, ossifying nucleus diameter, acetabular depth, and acetabular volume parameters. The average age of the patients was 23 months at initial surgery and 29 months at the time of revision surgery. No significant difference was found between the groups in terms of acetabular inclination angle, ossifying nucleus diameter, pelvic size, pelvic width, centre edge angle, acetabular volume, and depth. Contracted inferomedial capsule was found in 1 patient who underwent revision surgery and intact transverse acetabular ligament was seen in 1 patient. The loss of reduction in the remaining 11 patients was associated with high total anteversion of the femoral head and acetabulum. Correction of increased combined anteversion by femoral osteotomy can create a safe zone in terms of redislocation and can significantly contribute to the stability provided by capsulorrhaphy and pelvic osteotomy.


Change and correlates of change in high and low density lipoprotein cholesterol after six years: a prospective study.
Change and correlates of change in high and low density lipoprotein cholesterol (HDL and LDL) were studied in a prospective population-based study of 614 men and women in Rancho Bernardo, CA, 1972-1980. Correlations between baseline and follow-up examination an average of six years later were 0.72 for HDL and 0.68 for LDL, and 86% of HDL and 89% of LDL values were within +/- 30% of their original values. Predictions of HDL and LDL change were determined by multivariate analysis. Regression to the mean was the strongest single predictor of lipoprotein change and was more important than behavioral change. Among the behavioral variables, HDL change was positively associated with change in alcohol use in both sexes and with change in postmenopausal estrogen use in women and was inversely associated with change in obesity index in men. LDL change correlated positively with change in obesity index in both sexes. Change in reported cigarette use or exercise was unrelated to changes in HDL and LDL in this analysis. The similarity of lipoprotein values at baseline and follow-up suggests reasonable reliability and prognostic validity for a single HDL or LDL measurement. The multivariate analysis results generally confirm current cross-sectionally derived concepts about behavioral correlates of lipoproteins. However, the degree of regression to the mean indicates the wisdom of repeat measurements, particularly for persons with extreme values.


Constitutive androstane receptor (Car)-driven regeneration protects liver from failure following tissue loss.
Liver can recover following resection. If tissue loss is too excessive, however, liver failure will develop as is known from the small-for-size-syndrome (SFSS). The molecular processes underlying liver failure are ill-understood. Here, we explored the role and the clinical potential of Nr1i3 (constitutive androstane receptor, Car) in liver failure following hepatectomy. Activators of Car, various hepatectomies, Car(-/-) mice, humanized CAR mice, human tissue and ex vivo liver slice cultures were used to study Car in the SFSS. Pathways downstream of Car were investigated by in vivo siRNA knockdown. Excessive tissue loss causing liver failure is associated with deficient induction of Car. Reactivation of Car by an agonist normalizes all features associated with experimental SFSS. The beneficial effects of Car activation are relayed through Foxm1, an essential promoter of the hepatocyte cell cycle. Deficiency in the CAR-FOXM1 axis likewise is evident in human SFSS. Activation of human CAR mitigates SFSS in humanized CAR mice and improves the culture of human liver slices. Impaired hepatic Car-Foxm1 signaling provides a first molecular characterization of liver that fails to recover after tissue loss. Our findings place deficient regeneration as a principal cause behind the SFSS and suggest CAR agonists may bear clinical potential against liver failure. The unique regenerative capacity of liver has its natural limits. Following tissue loss that is too excessive, such as through extended resection in the clinic, liver failure may develop. This is known as small-for-size-syndrome (SFSS) and represents the most frequent cause of death due to liver surgery. Here we show that deficient induction of the protein Car, a central regulator of liver function and growth, is a cause of liver failure following extended resection; reactivation of Car through pharmacological means is sufficient to prevent or rescue the SFSS.


Supporting self-management in palliative care throughout the cancer care trajectory.
Despite increased survivorship and the subsequent need for chronic management of cancer, the association of self-management and palliative care is still emerging within cancer care. Routine and timely use of self-management strategies in the palliative setting can help reduce self-management burden and maximize quality of life. In this review, we consider the complementary relationship of self-management and palliative care and how they support living with cancer as a chronic illness. Recent studies provide evidence of support among patients, family caregivers and healthcare professionals for integration of self-management interventions into palliative cancer care. As a guiding framework, components of the revised Self and Family Management Framework correspond to the provision of palliative care across the care trajectory, including the phases of curative care, palliative care, end-of-life care and bereavement. Additional work among self-management partners facing cancer and other life-limiting illnesses, that is patients, family caregivers and healthcare professionals, would be useful in developing interventions that incorporate self-management and palliative care to improve health outcomes. There is an increasing acceptance of the complementarity of self-management and palliative care in cancer care. Their integration can support patients with cancer and their family caregivers across the care trajectory.


Three-dimensional spiral computed tomographic cysto-urethrography for post-traumatic complex posterior urethral strictures associated with urethral-rectal fistula.
To evaluate the value of three-dimensional spiral computed tomography/cysto-urethrography (CTCUG) in diagnosing posterior urethral strictures associated with urethrorectal fistulas (URF). Between June 2008 and March 2012, 38 patients with posterior urethral strictures associated with URFs were examined by CTCUG, retrograde urethrography (RUG) and cysto-urethrography (CUG). Urethral reconstruction was undertaken and URFs were surgically repaired in all patients. The length of the urethral defect, location and size of URFs were recorded. Data from radiological examinations were compared with surgical findings. No statistically significant difference was found in the length of stricture measured using CTCUG (4.31 ± 2.28 cm) or conventional urethrography (4.02 ± 3.12 cm; p > 0.05), However, the accuracy in determining the location of the stricture was higher with CTCUG (93.12%) than with conventional urethrography (70.59%; p < 0.05). CTCUG identified URFs in all 38 patients (100%), whereas URFs were only observed in 27 patients (71%) using conventional urethrography. In conclusion, CTCUG was more accurate, safer and provided more details of URFs and urethral defects than conventional urethrography in patients with posterior urethral strictures associated with URFs.


Risk and benefit perceptions of party drug use.
A cross-sectional survey of 372 regular ecstasy users was conducted to examine the benefits and risks perceived to be associated with the use of party drugs. A wide range of benefits and risks were reported across six drug types with some considered drug-specific. Commonly perceived risks included physical and psychological harms that were consistent with current harm reduction messages. Harm reduction campaigns may need to acknowledge benefits of drug use to ensure health promotion messages are considered credible and acceptable to users.


Kinetics of the inhibitory interaction of organophosphorus neuropathy inducers and non-inducers in soluble esterases in the avian nervous system.
Some published studies suggest that low level exposure to organophosphorus esters (OPs) may cause neurological and neurobehavioral effects at long term exposure. These effects cannot be explained by action on known targets. In this work, the interactions (inhibition, spontaneous reactivation and "ongoing inhibition") of two model OPs (paraoxon, non neuropathy-inducer, and mipafox, neuropathy-inducer) with the chicken brain soluble esterases were evaluated. The best-fitting kinetic model with both inhibitors was compatible with three enzymatic components. The amplitudes (proportions) of the components detected with mipafox were similar to those obtained with paraoxon. These observations confirm the consistency of the results and the model applied and may be considered an external validation. The most sensitive component (Eα) for paraoxon (11-23% of activity, I(50) (30 min)=9-11 nM) is also the most sensitive for mipafox (I(50) (30 min)=4 nM). This component is spontaneously reactivated after inhibition with paraoxon. The second sensitive component to paraoxon (Eβ, 71-84% of activity; I(50) (30 min)=1216 nM) is practically resistant to mipafox. The third component (Eγ, 5-8% of activity) is paraoxon resistant and has I(50) (30 min) of 3.4 μM with mipafox, similar to NTE (neuropathy target esterase). The role of these esterases remains unknown. Their high sensitivity suggests that they may either play a role in toxicity in low-level long-term exposure of organophosphate compounds or have a protective effect related with the spontaneous reactivation. They will have to be considered in further metabolic and toxicological studies.


[Muscle flap transfer of the treatment of infected tibial and malleolar fractures and chronic osteomyelitis of the tibia].
The aim of the study was to evaluate the results of treatment in patients with infected fractures or chronic osteomyelitis in the tibial and ankle regions by radical debridement of skeletal and soft tissues and coverage of the defect, using free flap transfer or muscle flap transposition. Between January 1, 2002 and December 31, 2004, 26 patients were treated by this method; 13 had infected tibial or ankle fractures and 13 showed osteomyelitis of the tibia. All patients, in the case of failure, would have been indicated for below-knee amputation. The group comprised six women and 20 men at an average age of 46 years (range, 10 to 67 years). In this retrospective study, the following data were recorded: type of injury (multiple trauma, combined trauma, single trauma), fracture type according to the AO classification, grade of injury in open fractures by the Gustillo and Anderson classification, number of previous operations in patients with infected fractures, microbiological findings in all patients before defect coverage with a flap, interval between the injury and flap coverage, number of post-operative complications, number of subsequent operations, period of relief for the treated limb, actual weight-bearing of the limb, patient's satisfaction with the therapy. Since one patient died of heart attack during follow-up, 25 patients (5 women and 20 men) were included in the final evaluation. The average follow-up was 27 months (range, 15 to 49 months). The healing of infection and union of bone were recorded in 21 patients (84 %). Healing with pseudoarthrosis development occurred in three patients (12 %). One patient (4 %) had to undergo leg amputation due to persistent secretion. The duration of treatment before coverage of the defect was on average 10 weeks (range, 4 weeks to 6 months) in the patients with infected fractures, and 9 years (range, 2 to 20 years) in the patients with osteomyelitis. Post-operative complications were recorded in seven patients (27 %). Impaired vascularization of the flap in the early post-operative period was found in two patients (8 %). In two patients (8 %) residual infected tissue under the flap resulted in purulent secretion. In three patients (12 %), at the time of evaluation, the lower extremity could not bear weight due to non-union of fractured bone. The use of free or transposition muscle is regarded as the optimal method for the treatment of extensive defects of soft tissues in limb traumatology. The advantages include: good quality coverage of the defect; ability of vascularized flap tissue to transport antibiotic to the defect area; long-term improved perfusion in the fracture region is important for fracture healing. The treatment of infected tibial and malleolar fractures by debridement and subsequent coverage of soft tissue defects, using muscle flap transfer, permits elimination of infection in most of the patients, but often requires subsequent surgery in order to provide biological stimulation for healing of defective fractures. Treatment of osteomyelitis of the tibia by this method is demanding, but has a good prospect of healing in a period shorter than is necessary for treatment without muscle flap transfer.


Attitudes of Swedish dentists to pain and pain management during dental treatment of children and adolescents.
This was to investigate the attitudes of Swedish general dental practitioners (GDPs) to pain perception in children and adolescents using a questionnaire survey. Their practice of pain control for dental treatment were also investigated. A questionnaire was sent to a random sample of 700 Swedish GDPs. Of these 421 (61%) were included in the analysis. About half of the dentists were of the opinion that children have difficulties in telling the difference between pain and discomfort and one third thought that young children report pain with some or great uncertainty. Swedish dentists tend to under use both local analgesia, analgesics and sedatives for pain management during dental treatment. Many dentists found it stressful to give local analgesia to preschool children. The results also showed that a group of dentists, about 35%, were more indifferent to their patient's experiences of pain and psychological management. Despite these results, experienced Swedish GDPs find little need for continuing education in pain management and local analgesia. Swedish GDPs under use local analgesia, analgesics and sedatives during dental treatment of children and adolescents. There is need for continuing education concerning pain management and an intensified discussion of attitudes to pain and pain management when treating children and adolescents.


Does coronary artery calcification in patients with diabetic nephropathy depend on the advancement of renal failure?
Calcium-phosphate disorders and vascular calcification are highly prevalent in patients with diabetes mellitus and nephropathy. The aim of the study was to compare the prevalence and advancement of vascular calcification in patients with end-stage diabetic nephropathy on peritoneal dialysis and diabetic patients with chronic renal disease stages 2-4. The study group included 31 patients with type 2 diabetes and diabetic nephropathy divided into 2 groups: 12 patients (aged 50-74 years: mean 58.6+/-8.8) undergoing peritoneal dialysis and 19 patients (aged 46-82 years; mean 65.8+/-9.7) with chronic kidney disease stages 2-4 (GFR range 24-78 ml/min/1.73 m2). Coronary artery calcification score, was assessed using multi-slice computed tomography. Coronary artery calcification score did not differ significantly between groups (CaSc values 1085.2 vs 452.4 AgU; NS). The patients undergoing peritoneal dialysis showed significantly higher levels of parathyroid hormone (658.2 vs. 74.3 pg/ml; p=0.001), fibrinogen (5.82 vs. 3.89 g/l; p<0.0001) and alkaline phosphatase (330.9 vs. 168.0 U/l; p=0.001). Despite more advanced abnormalities in calcium-phosphate balance parameters and more active inflammation in peritoneal dialysis subjects we failed to demonstrate any statistically significant difference in coronary artery calcification score between patients with diabetic nephropathy on peritoneal dialysis and those with chronic kidney disease stages 2-4.


Nutrient absorption in the preterm neonate.
The majority of what we know about the development of the absorptive process is derived from animal studies, studies in human fetal or stillborn tissues, and epidemiologic investigations derived from clinical experience. One can readily ascertain from this review that the absorption of nutrients in the intestine of the premature infant relates to a dynamic developmental process in which the consecutive stages are pre-programmed but can also be regulated by environmental factors. An understanding of these factors may lead to therapeutic intervention in premature infants, as has been the case for the developing lung and respiratory distress syndrome. Application of this knowledge to the critically ill premature infant in the intensive care unit will need to proceed cautiously, but it is likely to yield major benefits in terms of decreased short- and long-term morbidity in these highly vulnerable patients.


Protection of lungs from hyperoxic injury: gene expression analysis of cyclosporin A therapy.
We have previously shown that cyclosporin A (CsA), an inhibitor of protein phosphatase 2B (calcineurin), attenuates hyperoxia-induced reductions in murine lung compliance. CsA protected against hyperoxia-induced changes in neutrophil infiltration, capillary congestion, edema, and hyaline membrane formation. Gene expression studies were conducted to identify the gene expression patterns underlying the protective effects of CsA during hyperoxic lung injury. After 72 h of simultaneous treatment with >95% oxygen and CsA (50 mg x kg(-1) x day(-1)), RNA was isolated from murine lungs. RNA from treated and untreated lungs was reverse transcribed to cDNA, competitively hybridized, and used to probe 8,734 complimentary DNAs on the Incyte mouse GEM 1 array. Several known genes and expressed sequence tags (ESTs) showed increased (GenBank accession numbers: AA125385, AA241295, W87197, syntaxin, and cyclin G) or decreased [AA036517, AA267567, AA217009, W82577, uteroglobin, stromal cell-derived factor 1, and surfactant protein C (SP-C)] expression after hyperoxia. Hyperoxia-stimulated reductions in SP-C gene expression were confirmed through Northern blot analysis. The increase in gene expression of one expressed sequence tag (AA125385) with hyperoxia was reversed by CsA treatment. Sequence data demonstrated that this EST has high homology to murine cyclin B1. Western blot analysis did not demonstrate any changes in distal lung cyclin B1 expression after hyperoxia. Protein expression of cyclin B1 in the distal lung was observed in the endothelial cells, bronchiolar epithelial cells, and both the type I and type II alveolar epithelial cells. Further analysis of cyclin B1 may elucidate the protective actions of CsA in hyperoxic injury.


Anticipating drug side effects by comparative pharmacology.
Anticipating the likely side effect profile of drugs is an aspect of key importance in current drug discovery, development and marketing. It was recently shown that drug pairs having similar side effect profiles had also affinity for a common target. Acknowledging that most drugs have a rich polypharmacology, we provide proof that drugs related by side effect similarity have in fact affinities for multiple common targets beyond their primary targets and set the basis for the use of comparative pharmacology to anticipate drug side effects. Nomenclature issues to be able to identify and properly store drugs, targets and side effects from multiple public sources; the construction of drug networks from side effect similarity and the inference of common targets among them; polypharmacology and data completeness; methods for in silico target profiling; and comparative pharmacology and inference of common side effects. The reader is provided with a detailed step-by-step analysis of the entire process from predicting the target profile of a compound to anticipating its side effect profile, and a discussion on the particular needs and limitations found at each stage of the process through illustrative examples. Comparing preclinical pharmacology data obtained in vitro but also predicted in silico using modern virtual screening methods represents an attractive strategy to anticipate clinical drug side effects.


Iatrogenic thyrotoxicosis and the role of therapeutic plasma exchange.
Thyroid storm or severe thyrotoxicosis results from extreme thyroid hormone elevation. Therapy includes medical management to prevent hormone production, release, recycling, and peripheral conversion while stabilizing adrenergic tone. Thyroid dysfunction is the usual cause but it can be due to excessive thyroid hormone ingestion. Therapeutic plasma exchange (TPE) has been used to rapidly remove protein-bound thyroid hormone. American Society for Apheresis guidelines make a weak recommendation to perform TPE in selected patients in the treatment of thyrotoxicosis based on low quality evidence. We present a case of excessive thyroid replacement hormone ingestion treated by TPE. The patient presented with the clinical picture of thyroid storm, including cardiovascular compromise and massively elevated total and free T3 (525 ng/dL, nl 80-200 ng/dL and 28 pg/mL, nl 2.0-3.5 11 pg/mL), which failed medical therapy. A single, one plasma volume TPE was performed. Both total and free T3 demonstrated substantial declines immediately after TPE with the patient's mental status returning to near-normal. Thyroid hormone extraction efficiency and collection efficacy were calculated as 37.1% and 40.8%, respectively. Prior to discharge on day 6, the patient's compounding pharmacy indicated that a "bad batch" of bovine thyroid gland derived replacement hormone had been produced. TPE appears to be effective in removing protein bound thyroid hormone in extreme iatrogenic thyrotoxicosis.


Men's role in HIV/AIDS prevention for women: exploring different views.
Explore the role male partners should play in interventions that emerge from an empowerment perspective for the prevention of HIV/AIDS in women. Explore the social and cultural context, rationale and format for interventions if male partners are incorporated. Heterosexual women have become the most at risk group for HIV infection. Most of the HIV/AIDS prevention efforts have excluded the participation of male partners. Interventions with women have not been as affective as desired since the negotiation of safer sex method, such as the male condom, is not under their control. Thirteen focus groups were conducted in Puerto Rico, Dominican Republic and Mexico. Groups were conducted with HIV/AIDS prevention researchers, service providers, and heterosexual men and women who participated in HIV/AIDS prevention interventions. The taped conversations were transcribed and analyzed using content analysis according to a set of defined categories and subcategories. The majority of participants agreed that men must be incorporated in HIV prevention efforts with women. Many conditioned this participation, while some expressed their opposition. Regarding the ways of participation many favored working with men and women separately at the beginning and integrating at the end. They recommended considering working at a group level. The HIV/AIDS epidemic has put in the forefront the need to consider non-traditional approaches to promote behavior change. A group-base intervention with couples may be an effective way to prevent the HIV/AIDS epidemic.


[Osteoporosis treatment can be discontinued based on an individual assessment].
In most patients, treatment of osteoporosis is a long-term challenge. Because alendronate and zoledronic acid accumulate in bone with some persistent antifracture efficacy after therapy, it is reasonable to consider a "drug holiday" for low-risk patients. It is recommended that the duration and length of drug holiday should be individualized for each patient. For all other bisphosphonates data are limited. For other antiresorptive and anabolic agents "drug holiday" is not recommended.


Crohn's and Behçet's disease association presenting with superior vena cava thrombosis.
A 21-year-old male patient with a 6-year history of Crohn's disease presented with shoulder pain and edema in the neck and bilateral supraclavicular fossa. Color Doppler ultrasonography and computed tomography scan revealed bilateral thrombosis of the external jugular veins, brachiocephalic veins, and superior vena cava. Other etiologies were appropriately ruled out and the thrombosis was initially attributed to Crohn's disease. In the follow-up, the patient developed recurrent, painful orogenital ulcers and acne vulgaris-like skin eruptions. HLA tissue typing was HLA B-51. The diagnosis of Crohn's disease associated with Behçet's disease was made. Although there are several case reports describing such an association, a Medline research revealed that this was the first presentation of such an association with thrombosis. Thrombosis in unusual sites may reflect the uncommon association of Crohn's disease with hypercoagulable conditions such as Behçet's disease.


Hyperbranched fluoropolymer-polydimethylsiloxane-poly(ethylene glycol) cross-linked terpolymer networks designed for marine and biomedical applications: heterogeneous nontoxic antibiofouling surfaces.
Synthesis of terpolymer coatings composed of hyperbranched fluoropolymers cross-linked with bisamino-propyl poly(ethylene glycol) and bisamino-propyl polydimethylsiloxane (PDMS) was performed to generate antibiofouling surfaces. Nanoscale imaging and surface spectroscopy confirmed that this system possessed complex surface topographies and chemical compositions. Surface complexity was determined to be due to molecular interactions, phase segregation, and compositional gradients arising between the three components. A clear difference in surface behavior was observable before and after exposure to water. Antibiofouling characteristics were investigated by bovine serum albumin (BSA) adsorption studies; the terpolymer coating displayed a 60% greater resistance to protein adsorption in comparison to the fouling of a commercial antibiofouling silicone coating. The unique surface topography, topology, and chemical heterogeneity expressed at a variety of scales provide a robust regime for the generation of hardy, complex surfaces known to incorporate characteristics appropriate for antibiofouling applications. Thorough assessment of thermal responses and mechanical properties in relevant environments demonstrated a formulation platform immediately appropriate for consideration in marine and in vivo applications.


Radiocarpal arthroscopy portals and normal anatomy.
Wrist arthroscopy is now an accepted technique in the evaluation of radiocarpal intra-articular pathology. An understanding of the surface anatomic landmarks and articular anatomy is required to safely and effectively perform the technique. Multiple portals are used to arthroscopically view the radiocarpal joint and provide access for irrigation and surgical instruments.


Chart busters.
Poor design of bedside observational charts is causing staff to miss patient deterioration, a study has shown.


Thermoresponsive Catechol Based-Polyelectrolyte Complex Coatings for Controlled Release of Bortezomib.
To overcome the high relapse rate of multiple myeloma (MM), a drug delivery coating for functionalization of bone substitution materials (BSM) is reported based on adhesive, catechol-containing and stimuli-responsive polyelectrolyte complexes (PECs). This system is designed to deliver the MM drug bortezomib (BZM) directly to the anatomical site of action. To establish a gradual BZM release, the naturally occurring caffeic acid (CA) is coupled oxidatively to form poly(caffeic acid) (PCA), which is used as a polyanion for complexation. The catechol functionalities within the PCA are particularly suitable to form esters with the boronic acid group of the BZM, which are then cleaved in the body fluid to administer the drug. To achieve a more thorough control of the release, the thermoresponsive poly(N-isoproplyacrylamide-co-dimethylaminoethylmethacrylate) (P(NIPAM-co-DMAEMA)) was used as a polycation. Using turbidity measurements, it was proven that the lower critical solution temperature (LCST) character of this polymer was transferred to the PECs. Further special temperature dependent attenuated total reflection infrared spectroscopy (ATR-FTIR) showed that coatings formed by PEC immobilization exhibit a similar thermoresponsive performance. By loading the coatings with BZM and studying the release in a model system, via UV/Vis it was observed, that both aims, the retardation and the stimuli control of the release, were achieved.


Activation by adrenaline of a low-conductance G protein-dependent K+ channel in mouse pancreatic B cells.
Insulin is produced and secreted by the B cells in the endocrine pancreas. In vivo, insulin secretion is under the control of a number of metabolic, neural and hormonal substances. It is now clear that stimulation of insulin release by fuel secretagogues, such as glucose, involves the closure of K+ channels that are sensitive to the intracellular ATP concentration (KATP channels). This leads to membrane depolarization and the generation of Ca2(+)-dependent action potentials. The mechanisms whereby hormones and neurotransmitters such as adrenaline, galanin and somatostatin, which are released by intraislet nerve endings and the pancreatic D cells, produce inhibition of insulin secretion are not clear. Here we show that adrenaline suppresses B-cell electrical activity (and thus insulin secretion) by a G protein-dependent mechanism, which culminates in the activation of a sulphonylurea-insensitive low-conductance K+ channel distinct from the KATP channel.


Computerized histopathologic assessment of malignant potential. III. Refinements of measurement and data analysis.
The nucleolar area of uveal melanomas, measured from standard hematoxylin-and-eosin-stained microslides , has been shown in previous work to correlate well with survival following enucleation of the tumor-bearing eye. Despite this correlation, the accuracy of the original system for measuring nucleolar area was affected by several sources of error: (1) the algorithm by which area was computed underestimated true area, (2) geometric and optical factors caused overestimation of nucleolar area unless measured in the center of the microscopic field of view and (3) the area of small nucleoli, as the result of several possible mechanisms, contains less useful information than the area of large nucleoli. This paper presents methods introduced to reduce error from these sources and demonstrates that the predictive value of nucleolar measurements is relatively insensitive to high levels of random variation.


Susceptibility of TNF-alpha-deficient mice to Trypanosoma congolense is not due to a defective antibody response.
C57BL/6 mice deficient in one or two copies of the gene for tumor necrosis factor alpha (TNF-alpha) were more susceptible to Trypanosoma congolense infection than their resistant, wild-type counterparts. The number of TNF-alpha genes was correlated with the capacity to control parasitaemia and with survival time. Absence of TNF-alpha resulted in a diminished capacity to form germinal centres in lymph nodes and spleen. Since germinal centres are involved in antibody production and affinity maturation, the susceptibility of the TNF-alpha-deficient mice could have been due to this secondary defect. Despite the lack of the germinal centres, the antibody responses to internal and exposed trypanosome antigens and to non-trypanosome antigens were not significantly different. Also the relative avidities measured in infected sera did not significantly differ between the two mouse strains. These data suggest that the role of TNF-alpha in control of T. congolense was not due to its role in the development of an antibody response.


Antimicrobial activity of doubly-stapled alanine/lysine-based peptides.
In this study, we examined the potential of Verdine's double-stapling system for the de novo design of amphipathic helical antimicrobial peptides. We designed, synthesized, and tested a prototypical doubly-stapled helix of an alanine/lysine based model sequence, which showed reasonable antimicrobial activities and highly increased proteolytic stability. We then show that its hemolytic activity as well as antimicrobial activities can be further manipulated through the systematic modifications. Overall, the preliminary results obtained from this study imply that the doubly-stapled helices of short peptides can serve as a highly promising scaffold for the rational design of potent, selective, and metabolically stable antimicrobial peptides that can combat against the growing problems of antibiotic-resistance.


Unenhanced flow-independent MR venography by using signal targeting alternative radiofrequency and flow-independent relaxation enhancement.
The purpose of this study was to provide the initial description of the signal targeting using alternative radiofrequency and flow-independent relaxation enhancement (STARFIRE) technique and demonstrate clinical feasibility by imaging the deep and superficial veins of the lower extremities in a small cohort of healthy subjects and patients with peripheral venous disease. STARFIRE is a flow-independent technique for unenhanced magnetic resonance (MR) angiography. An adiabatic inversion pulse is applied to all spins on alternative acquisitions followed by complex subtraction. Blood vessels appear bright with uniform suppression of fat and muscle signals. Following approval by the hospital institutional review board and with written, informed consent, six healthy patients and four with peripheral venous disease were studied. The results demonstrate the clinical feasibility of STARFIRE to depict the deep and superficial venous systems of the lower extremities, and suggest the need for addition clinical evaluation.


Harvey Cushing and the Oxford connection.
Without apparently relaxing or detracting from his full clinical routine, Cushing was able, throughout his career, to cater to a panoply of interests. In an age when travel was, presumably, slower by ship and by train, his journeys across the ocean to Europe and the British Isles were legion. Primarily because of his relationship with Osler, then Sherrington, Cairns and his other friends, Oxford became an often visited and cherished place. The award of an honorary degree and final tribute from colleagues, admirers and students seemed a fitting climax to Cushing's connection with that city and its ancient university. Such a connection, enhanced by his students, his writings, his scholarship and his bibiliographies, became a natural extension of his personality.


Acute encephalopathy in the immune-compromised child: never forget toxoplasmosis.
Toxoplasma gondii is an opportunistic parasite, which very unusually may cause acute encephalitis in patients undergoing chemotherapy or hematopoietic stem cell transplant. The prognosis is usually dismal also because of late diagnosis, depending on the limited availability of specific diagnostic tools. An early diagnosis allows effective intervention with specific antibiotics, which may provide a chance for cure. We report 2 cases of cerebral toxoplasmosis in which the use of polymerase chain reaction on cerebrospinal fluid allowed a prompt diagnosis and specific therapy, which was followed by clinical response and negativization at follow-up studies of T. gondii genome on cerebrospinal fluid by polymerase chain reaction and by brain imaging.


Chan-Evans-Lam Amination of Boronic Acid Pinacol (BPin) Esters: Overcoming the Aryl Amine Problem.
The Chan-Evans-Lam reaction is a valuable C-N bond forming process. However, aryl boronic acid pinacol (BPin) ester reagents can be difficult coupling partners that often deliver low yields, in particular in reactions with aryl amines. Herein, we report effective reaction conditions for the Chan-Evans-Lam amination of aryl BPin with alkyl and aryl amines. A mixed MeCN/EtOH solvent system was found to enable effective C-N bond formation using aryl amines while EtOH is not required for the coupling of alkyl amines.


Real-time detection of H5N1 influenza virus through hyperbranched rolling circle amplification.
An isothermal amplification method was developed for the sensitive detection of the H5N1 influenza virus. The padlock probe specifically bound to the H5N1 target and circularized with T4 DNA ligase enzyme. Then this circular probe was amplified by hyperbranched rolling circle amplification (HRCA) using Phi29 DNA polymerase. The fluorescence intensity was recorded at different intervals by intercalation of SYBR green molecules into the double-stranded product of the HRCA reaction. At an optimum time of 88 min, a calibration plot with fine linearity was obtained. Using HRCA based on a padlock probe and Phi29 DNA polymerase, high selectivity and sensitivity were achieved. The biosensor response was linear toward H5N1 in the concentration range from 10 fM to 0.25 pM, with a detection limit of 9 fM at a signal/noise ratio of 3. By replacing the heat shock with pH shock, not only was the procedure for detection of H5N1 influenza simplified, but also the DNA molecules were protected from possible breaking at high temperature.


Synthesis of an HIV-1 Tat transduction domain-rotavirus enterotoxin fusion protein in transgenic potato.
A DNA fragment encoding a 12-amino acid (aa) HIV-1 Tat transduction peptide fused to a 90-aa murine rotavirus NSP4 enterotoxin protein (Tat-NSP4(90)) was transferred to Solanum tuberosum by Agrobacterium tumefaciens-mediated transformation. The fusion gene was detected in the genomic DNA of transformed plant leaf tissues by PCR DNA amplification. The Tat-NSP4(90 )fusion protein was identified in transformed tuber extracts by immunoblot analysis using anti-NSP4(90) and anti-Tat as the primary antibodies. Enzyme-linked immunosorbent assay results showed that the Tat-NSP4(90) fusion protein made up to 0.0015% of the total soluble tuber protein. The synthesis of Tat-NSP4(90) fusion protein in transformed potato tuber tissues demonstrates the feasibility of plant cell delivery of the HIV-1 Tat transduction domain as a carrier for non-specific targeting of fused antigens to the mucosal immune system.


[Clinical study on utilizing free palatal mucosa flap in reconstructing peri-implant attached soft tissue].
To evaluate the results and clinical characteristics of free palatal mucosa flap in reconstructing peri-implant attached soft tissue. 126 cases with partial edentulous or edentulous were undergone soft tissue reconstruction and implant treatment from July 1997 to June 2005. A total of 388 implants were placed. The mean follow-up period was over 13 months. Mucosa flaps were measured at the operation and compared the size changes one year after operation. Necrosis occurred in 3 mucosa flaps out of 126 cases 10 days postoperatively. Mean shrinkage of mucosa flap was 56%(37%-70%). No loss of implant was found in the last follow-up and attached soft tissue width was over 3 mm in 371 implants. Eight implants were diagnosed as peri-implantitis (2.06%). It is effective and predictable to reconstruct peri-implant attached soft tissue with free palatal mucosa flap.


Intact actin filaments are required for cytosolic phospholipase A2 translocation but not for its activation by norepinephrine in vascular smooth muscle cells.
Cytosolic phospholipase A(2) (cPLA(2)) is activated and translocated to the nuclear envelope by various vasoactive agents, including norepinephrine (NE), and releases arachidonic acid (AA) from tissue phospholipids. We previously demonstrated that NE-induced cPLA(2) translocation to the nuclear envelope is mediated via its phosphorylation by calcium/calmodulin-dependent kinase-II in rabbit vascular smooth muscle cells (VSMCs). Cytoskeletal structures actin and microtubule filaments have been implicated in the trafficking of proteins to various cellular sites. This study was conducted to investigate the contribution of actin and microtubule filaments to cPLA(2) translocation to the nuclear envelope and its activation by NE in rabbit VSMCs. NE (10 microM) caused cPLA(2) translocation to the nuclear envelope as determined by immunofluorescence. Cytochalasin D (CD; 0.5 microM) and latrunculin A (LA; 0.5 microM) that disrupted actin filaments, blocked cPLA(2) translocation elicited by NE. On the other hand, disruption of microtubule filaments by 10 microM colchicine did not block NE-induced cPLA(2) translocation to the nuclear envelope. CD and LA did not inhibit NE-induced increase in cytosolic calcium and cPLA(2) activity, determined from the hydrolysis of l-1-[(14)C]arachidonyl phosphatidylcholine and release of AA. Coimmunoprecipitation studies showed an association of actin with cPLA(2), which was not altered by CD or LA. Far-Western analysis showed that cPLA(2) interacts directly with actin. Our data suggest that NE-induced cPLA(2) translocation to the nuclear envelope requires an intact actin but not microtubule filaments and that cPLA(2) phosphorylation and activation and AA release are independent of its translocation to the nuclear envelope in rabbit VSMCs.


Some aspects of structural studies on aspartic proteinases.
This paper gives a brief overview over the differences and similarities in the structure of aspartic proteinases presently available. Comparison of the three-dimentional structure of different aspartic proteinases by a common intramolecular coordinate system have been performed. The intramolecular movable subdomains have been localized and the role of motion in substrate binding and zymogen activation is discussed.


H-ferritin is the major source of iron for oligodendrocytes.
There is a critical relationship between oligodendrocyte development, myelin production, and iron bioavailability. Iron deficiency leads to hypomyelination both in humans and animal models, and the neurological sequelae of hypomyelination are significant. Therefore, understanding molecular mechanisms of iron import into oligodendrocytes is necessary for devising effective strategies for iron supplementation. Although transferrin has been considered as an essential component of oligodendrocyte media in culture, oligodendrocytes in vivo lack transferrin receptors. We have established that receptors for H-ferritin (HF) exist on cells of oligodendroglial lineage and that uptake of extracellular HF by oligodendrocyte progenitors is via receptor mediated endocytosis. These data strongly argue that ferritin is a major source of iron for oligodendrocytes. In this study, we demonstrate that media deficient in transferrin results in loss of viability of oligodendrocyte progenitors in culture. Cell loss could be prevented by supplementing the media with HF. Moreover, the addition of extracellular HF stimulates development of oligodendrocyte progenitor cells (OPCs) by increasing expression of myelin basic protein (MBP) and olig2 proteins without increasing their proliferation. The effect of HF on the OPCs could be mimicked by addition of membrane permeable 3,5,5-trimethylhexanoyl ferrocene (TMH-Fe) as an iron source to the media, but not membrane-impermeable ferric ammonium citrate. Overall, therefore, our results demonstrate the importance of iron for OPCs viability and differentiation and identify extracellular HF as a critical source of iron for oligodendrocytes. Given that ferritin receptors, but not transferrin receptors can be demonstrated on oligodendrocytes in vivo, the delivery of iron to oligodendrocytes via ferritin may be the more biological relevant delivery system.


Migration of plasticizers phthalates, bisphenol A and alkylphenols from plastic containers and evaluation of risk.
This study investigates the potential migration of plasticisers, plastic components and additives from several plastic water bottles. Compounds studied were phthalates (dimethyl phthalate, di-n-butyl phthalate, benzylbutyl phthalate, bis(2-ethylhexyl) phthalate), bis(2-ethylhexyl) adipate, octylphenol, 4-nonylphenol and bisphenol A. Polycarbonate (PC), high-density polyethylene (HDPE), low-density polyethylene (LDPE), polyethylene terephthalate (PET) and polystyrene (PS) plastics used in the water bottling sector were tested using three kinds of total or specific migration tests: (1) standard method UNE-EN ISO 177; (2) ultrasonic forced extraction; and (3) standard method UNE-EN 13130-1. In addition, bottled waters contained in different plastic materials were analysed to determine the potential migration of target compounds in real conditions. In all cases, samples were solid-phase extracted using Oasis HLB 200 mg cartridges and analysed using GC-MS in scan-acquisition mode. Bisphenol A and 4-nonylphenol were detected in incubated samples, indicating that migration from food plastics can occur at the experimental conditions tested. The total daily intake was calculated according to the levels detected in bottled water and the assessment of the consumers' risk was evaluated taking into consideration toxicological and legislative values.


Anomalous toluene transport in model segmented polyurethane-urea/clay nanocomposites.
The kinetics of liquid solvent sorption in polymeric systems and their nanocomposites often deviate from normal Fickian behaviour. This needs to be understood and interpreted, in terms of their underlying mechanistic origins. In the present study, the results of time dependent toluene sorption measurements in model segmented polyurethane-urea/clay nanocomposites have been analysed at room temperature. The studies revealed pronounced S-shaped sorption curves and unusually higher swelling of the nanocomposites compared to the neat polyurethane-urea matrix. Dynamic mechanical analysis (DMA) and small angle X-ray scattering (SAXS) measurements on the nanocomposites in the dry and liquid toluene saturated state have been carried out. The DMA studies revealed a significant decrease in the α relaxation temperature and storage modulus of the nanocomposites in the swollen state compared to the dry samples. The SAXS results showed that the nanoclay dispersion morphology transformed from intercalation in the dry state to exfoliation in the swollen state and the interdomain distance between hard segments increased upon swelling. Thermodynamic analysis of the Flory-Huggins interaction parameter (χ) of nanocomposite/toluene systems revealed increasingly negative χ values with increased clay loading. These results imply a significant plasticization effect of toluene on the nanocomposites. An interpretation of these data, which relates the abovementioned results, is presented in the framework of differential swelling stress (DSS) induced deviation from Fickian transport characteristics. We expect that these findings and methods may provide new insight into the analysis of the solvent diffusion process in heterogeneous polymers and their nanocomposites.


Antioxidants and oxidative stress in BAL fluid of atopic asthmatic children.
Earlier studies in adults have indicated that increased oxidative stress may occur in the blood and airways of asthmatic subjects. Therefore the aim of this study was to compare the concentrations of antioxidants and protein carbonyls in bronchoalveolar lavage fluid of clinically stable atopic asthmatic children (AA, n = 78) with our recently published reference intervals for nonasthmatic children (C, n = 124). Additionally, lipid peroxidation products (malondialdehyde) in bronchoalveolar lavage fluid and several antioxidants in plasma were determined. Bronchoalveolar lavage concentrations (median and interquartile range) of ascorbate [AA: 0.433 (0.294-0.678) versus C: 0.418 (0.253-0.646) micromol/L], urate [AA: 0.585 (0.412-0.996) versus C: 0.511 (0.372-0.687) micromol/L], alpha-tocopherol [AA: 0.025 (0.014-0.031) versus C: 0.017 (0.017-0.260) micromol/L], and oxidized proteins as reflected by protein carbonyls [AA: 1.222 (0.970-1.635) versus C: 1.243 (0.813-1.685) nmol/mg protein] were similar in both groups (p > 0.05 in all cases). The concentration of protein carbonyls correlated significantly with the number of eosinophils, mast cells, and macrophages in AA children only. Concentrations of oxidized proteins and lipid peroxidation products (malondialdehyde) correlated significantly in AA children (r = 0.614, n = 11, p = 0.044). Serum concentrations of ascorbate, urate, retinol, alpha-tocopherol, beta-carotene, and lycopene were similar in both groups whereas alpha-carotene was significantly reduced in asthmatics. Overall, increased bronchoalveolar lavage eosinophils indicate ongoing airway inflammation, which may increase oxidatively modified proteins as reflected by increased protein carbonyl concentrations.


Experimental production of rabbit mucoid enteritis.
Rabbit mucoid enteritis (mucoid enteropathy) is a subacute fatal disease of weanling rabbits with unknown cause. Mucoid enteritis was experimentally produced by ligating the large intestines in rabbits. Of the rabbits with ligated cecum and those with ligated colon, 70% and 45%, respectively, had excessive production of mucus and passed large amounts of mucus with feces, closely resembling the naturally occurring mucoid enteritis. Injection of oxytetracycline into the cecum at the time of ligation prevented the development of mucoid enteritis, and injection of cholestyramine markedly reduced the frequency of the disease in the rabbits with ligated cecum.


Responses of single units in sixth lumbar dorsal root ganglion of female rats to mechanostimulation relevant for lordosis reflex.
1. The activity of single units (n = 312) was recorded from dorsal root ganglion L6 in female rats; 84% received input from cutaneous mechanoreceptors. 2. Among cutaneous mechanoreceptive units (n = 263), 22% responded to individual guard hair movement, 18% to down hair, 11% to clitoral hair, and 14% to stimulation of tylotrich hair-haarscheibe (type I) receptors, 5% responded to punctate skin deformation, but not hair movement of pressure, and 18% responded to pressure. 3. No significant differences between estrogen-treated and untreated ovariectomized rats were observed in receptive-field size, or von Frey hair, or pressure threshold of any given type of unit. 4. The lordosis reflex of female rats is triggered by pressure, but not hair deflection, on skin regions innervated by dorsal root L6 (10). Stimulation from the male rat mounting would cause a barrage of action potentials from most of the unit types identified here, but only pressure units and type I units gave sustained responses to a lordosis-triggering type of pressure stimulation.


Widespread Anthropogenic Nitrogen in Northwestern Pacific Ocean Sediment.
Sediment samples from the East China and Yellow seas collected adjacent to continental China were found to have lower δ15N values (expressed as δ15N = [15N:14Nsample/15N:14Nair - 1] × 1000‰; the sediment 15N:14N ratio relative to the air nitrogen 15N:14N ratio). In contrast, the Arctic sediments from the Chukchi Sea, the sampling region furthest from China, showed higher δ15N values (2-3‰ higher than those representing the East China and the Yellow sea sediments). Across the sites sampled, the levels of sediment δ15N increased with increasing distance from China, which is broadly consistent with the decreasing influence of anthropogenic nitrogen (NANTH) resulting from fossil fuel combustion and fertilizer use. We concluded that, of several processes, the input of NANTH appears to be emerging as a new driver of change in the sediment δ15N value in marginal seas adjacent to China. The present results indicate that the effect of NANTH has extended beyond the ocean water column into the deep sedimentary environment, presumably via biological assimilation of NANTH followed by deposition. Further, the findings indicate that NANTH is taking over from the conventional paradigm of nitrate flux from nitrate-rich deep water as the primary driver of biological export production in this region of the Pacific Ocean.


Variability of exposure measurements in environmental epidemiology.
In studies in environmental epidemiology, exposure to harmful agents is often highly variable in time and space. It is not usually possible to measure the relevant, personal exposure of study subjects to these agents directly. Instead, exposure measurements are performed at fixed sites and/or for limited periods of time in many cases. Such measurements are imperfect in the sense that they only approximate the "true" personal exposure of study subjects. When measures of exposure are highly variable in time and space, single measurements approximate the true exposure only to a limited extent. The variability of measures of exposure can be investigated by repetition of the measurements in time and space. Analysis of variance techniques can be used to separate the within-subject or "error" variance from the between-subjects or true variance. Computation of the ratio between the error variance and the true variance is a useful technique to evaluate the potential bias in correlation and regression coefficients calculated with these measures of exposure. Using data from a number of different studies, the authors have estimated the variance ratio of lead exposure and nitrogen dioxide exposure variables. The results suggest that these ratios may be large. Empirical illustrations are given of bias in regression coefficients of childhood blood levels on different lead exposure variables. It is recommended that pilot studies be performed more routinely to estimate the magnitude of the variance ratios of exposure variables of interest in studies in environmental epidemiology.


Synthesis and biological evaluation of alpha-MSH analogues substituted with alanine.
The influence of single amino acid replacements by alanine on the binding affinity and biological activity of alpha-MSH in B16 murine melanoma cells has been studied systematically. alpha-MSH analogues were synthesized by solid-phase peptide synthesis and their binding affinities to the melanocortin receptor expressed by B16 mouse melanoma cells were determined using a radioreceptor assay. Biological activity of the analogues was determined by measuring tyrosinase stimulation. Relative activity and affinity data were generally in agreement with earlier results using terminal deletion fragments of alpha-MSH, but the alanine scan revealed important new insights into the role of individual residues. The three terminal amino acids at either end were not necessary for binding or activity, with amino acids 4-9 forming a core sequence required for receptor binding and triggering of the biological response. It was observed that replacement of the glutamic acid residue in position 5 was possible without loss of affinity or activity, whereas replacement of Met4 resulted in a 100-fold loss of binding affinity and biological activity. Each residue within the conserved melanocortin sequence His-Phe-Arg-Trp was shown to be essential with Phe7, Arg8, and Trp9 being the most sensitive to replacement by alanine. Generally, there was a rank correlation between binding affinity and tyrosinase stimulation within the group of analogues studied. Tyrosinase activity was less affected by alanine substitution than binding affinity, which suggests that full receptor binding is not required for maximum biological response.


Enantioselective de novo synthesis of 4-deoxy-D-hexopyranoses via hetero-Diels-Alder cycloadditions: total synthesis of ezoaminuroic acid and neosidomycin.
The de novo synthesis of carbohydrates constitutes an important aspect of organic chemistry, and its application toward deoxy sugars is particularly noteworthy in targeting biologically active compounds. The enantioselective preparation of 4-deoxy-D-ribo-, 4-deoxy-D-lyxo-, and 4-deoxy-D-xylo-hexopyranosides, along with their uronate counterparts has been successfully accomplished using hetero-Diels-Alder reactions as the key step. Jacobsen chromium(III) catalyst and a titanium-binaphthol complex have been used to successfully catalyze diene and aldehyde cycloadditions, leading to optically active dihydropyran templates. 6-Hydroxydesosamine, orthogonally protected ezoaminuroic acid, and neosidomycin were synthesized using a comparative study. Also, a novel chiron approach to 4-deoxy-lyxo-hexopyranosiduronic acid methyl ester derivatives was efficiently accomplished starting from readily accessible starting materials. This work represents a systematic and comprehensive study toward a de novo synthesis of 4-deoxy-hexopyranoses via enantioselective hetero-Diels-Alder reactions.


Epidermal Langerhans cells resistance to solar-simulated radiation in actinic prurigo patients with low minimal erythema dose.
Actinic prurigo is a chronic photodermatosis of unclear pathogenesis. Epidermal Langerhans cell resistance to migration after ultraviolet radiation exposure has been proposed as a possible mechanism, as occurs in polymorphic light eruption patients. The purpose of this study was to evaluate the effect of solar-simulated radiation (SSR) on epidermal Langerhans cells in the uninvolved skin of actinic prurigo patients. Fifteen patients with actinic prurigo participated in the study. A biopsy from the uninvolved and unirradiated skin of the left buttock was performed, and another from the uninvolved skin of the right buttock, 72 hours after exposure to two MEDs of SSR. Immunohistochemistry staining was used to identify Langerhans cells (CD1a) in all samples. In actinic prurigo patients with normal MED, there was a significant decrease in the number of epidermal Langerhans cells on the buttock skin exposed to two MED of SSR compared with the unirradiated buttock skin (P = .02 and .035 respectively). On the contrary, in patients with low MED there were no significant differences in the number of epidermal Langerhans cells between irradiated and unirradiated skin (P = .39). Epidermal Langerhans cells migration after ultraviolet radiation exposure is decreased in actinic prurigo patients with low MED as has been reported in PLE patients, especially, those with low MED or positive UVB provocation tests. Langerhans cells resistance could be part of a common pathogenic mechanism in these two photodermatoses.


Diagramming patients' views of root causes of adverse drug events in ambulatory care: an online tool for planning education and research.
Diagram patients' views of the causes of adverse drug events (ADEs) in ambulatory care, examine characteristics of causes reported by patients, and identify those that have been studied in the medical and social science literatures. Twenty-two primary care patients were interviewed using a root cause analysis approach. Diagrams derived from interviews were consolidated and displayed online as a composite interactive causal diagram. Patient-reported causes were compared to evidence in the social science and medical literatures. Patients ascribed 164 causes to ADEs occurring through eight major pathways, including medication nonadherence, prescriber-patient miscommunication, patient medication error, failure to read medication label/insert, polypharmacy, patient characteristics, pharmacist-patient miscommunication, and self medication. Most frequently reported causes were intrapsychic and interpersonal in nature. Most patient-reported causes have been studied, however, several practical and motivational antecedents lack research. Conducting root cause analysis with patients reveals multiple logically linked aspects of medication safety in community settings that merit further research and consideration in patient and prescriber education. This causal diagram provides a broadly accessible planning tool for reducing ambulatory ADEs by showing a comprehensive picture of potential causes, identifying causal factors supported by evidence, and disclosing likely consequences of change efforts. Also, patient-centered medication safety strategies should address psychological and practical barriers patients face in their everyday lives.


Osteoarthritis and articular cartilage use, disuse, and abuse: experimental studies.
Recent investigations have distinguished 3 different patterns of articular cartilage use that have different consequences: normal use, marked decrease use (disuse), and use that damages the tissue (abuse). In vitro cyclic loading of cartilage in the physiologic range stimulates matrix synthesis. In vivo, lifelong moderate and probably even strenuous joint use does not cause cartilage degeneration in normal animal joints, i.e., joints with normal articular surfaces, alignment, stability, innervation, and muscle control. In contrast, static loading or the absence of loading causes matrix degradation and eventually loss of joint function. Abuse of normal joints by single or repetitive impact loads can lead to progressive degeneration of the articular surface. Normal use of abnormal joints, in particular joints with incongruous articular surfaces, malalignment, instability, or disturbances of joint or muscle innervation may also increase the risk of degenerative joint disease.


Tick paralysis: electrophysiologic studies.
A patient with tick paralysis had motor and sensory nerve conduction studies before and after removal of an engorged tick. The amplitudes of muscle action potentials evoked by stimulation of motor nerves were reduced initially, returning to normal after the tick was removed. Distal motor and sensory latencies also shortened after removal, and conduction velocities were improved 6 months later. Direct stimulation of muscle produced a normal response, and tests of neuromuscular transmission were normal, including the response to edrophonium. These findings are compatible with experimental results showing effects of the toxin on motor nerve terminals as well as on large sensory and motor nerves.


Determinants of sequence-specific DNA methylation: target recognition and catalysis are coupled in M.HhaI.
Sequence specificity studies of the wild-type bacterial DNA cytosine C5 methyltransferase HhaI were carried out with cognate (5'GCGC3') and noncognate DNA substrates containing single base pair changes at the first and the fourth position (underlined). Specificity for noncognate site methylation at the level of kcat/KDDNA is decreased 9000-80000-fold relative to the cognate site, manifested through changes in methylation, or a prior step, and changes in KDDNA. Analysis of a new high-resolution enzyme-DNA cocrystal structure provides a partial mechanistic understanding of this discrimination. To probe the significance of conformational transitions occurring prior to catalysis in determining specificity, we analyzed the double mutant (H127A/T132A). These amino acid substitutions disrupt the interface between the flexible loop (residues 80-99), which interacts with the DNA minor groove, and the active site. The mutant's methylation of the cognate site is essentially unchanged, yet its methylation of noncognate sites is decreased up to 460-fold relative to the wild-type enzyme. We suggest that a significant contribution to M.HhaI's specificity involves the stabilization of reaction intermediates prior to methyl transfer, mediated by DNA minor groove-protein flexible loop interactions.


Single-nucleotide polymorphisms in genes encoding toll-like receptor -2, -3, -4, and -9 in case-control study with breast cancer.
Genetic susceptibility to cancer is multifactorial, and it is known that impairment of the immune system could contribute to risk for getting cancer. Single-nucleotide polymorphisms (SNPs) of Toll-like receptor (TLR) 2, TLR3, TLR4, and TLR9 genes, which are important for innate immunity, were analyzed for the association with breast cancer. The SNPs comprised TLR2 (c.597T>C), TLR2 (c.1350T>C), TLR3 (c.1377C>T), TLR4 (c.896A>G), and TLR9 (c.1635A>G). The allelic and genotypic frequencies of these TLR SNPs were compared between patients (n = 130) and controls (n = 101) in a case-control study from Croatia. TLR SNPs were not significantly different. From the population genetics viewpoint, we found that a hypomorphic variant of TLR4 (p.Asp299Gly) allele has no specific allelic frequency (8.4%) in the Croatian population (n = 496) compared to other Caucasians (6.5-10%). These results suggest that polymorphisms in tested TLR genes are not likely to be associated with increased risk for developing breast cancer.


[Efficacy of standard antiviral therapy retreatment following interferon treatment failure in chronic hepatitis C patients].
To investigate the therapeutic efficacy of standard antiviral therapy applied after interferon (IFN) treatment failure in patients with chronic hepatitis C (CHC). CHC patients who completed a 48-week course of IFN therapy (pegylated (Peg)-IFNa-2a at 180 mug, qw, ih with or without ribavirin (RBV) at 15 mg/kg/w) in our hospital between January 2009 and June 2012 but who showed no response (at week 48) or who relapsed (at week 72) were enrolled in the study. Prior to initiating the 48-week course of retreatment therapy (Peg-IFNa-2a plus RBV as above), the hepatitis C virus (HCV) genotype was detected and the viral load measured (baseline) by PCR of HCV RNA. Each patient's response to therapy was classified as follows: baseline vs. week 4 (rapid virological response, RVR), vs. weeks 12 and 24 (early virological response, EVR), vs. week 48 (end of treatment virological response, ETVR) and vs. week 72 (sustained virological response, SVR). Of the total 235 cases administered retreatment therapy, 60.0% (n = 140) achieved RVR, 77.4% (n = 182) achieved EVR, 83.8% (n = 197) achieved ETVR, 68.0% (n = 68%) achieved SVR, and 15.7% (n = 37) relapsed. Stratification analysis of recurrence (n = 158) and non-responsive (n = 77) sub-groups showed that the recurrence group experienced significantly higher rates of RVR, EVR, ETVR and SVR, but a significantly lower rate of relapse. Stratification analysis of genotype 1b carrier (n = 206) and non-1b carrier (n = 29) sub-groups showed that the 1b carriers had significantly lower rates of RVR, EVR, ETVR and SVR, but a significantly higher rate of relapse. Finally, the patients who achieved RVR (vs. non RVR, n = 95) and EVR (vs. non-EVR, n = 53) showed higher rates of SVR and ETVR. CHC patients who fail to respond to the initial course of standard IFN-based therapy may achieve SVR upon retreatment, especially those infected with the HCV genotype 1b.


Characterization of KPC-encoding plasmids from two endemic settings, Greece and Italy.
Global dissemination of KPC-type carbapenemases is mainly associated with the spread of high-risk clones of Klebsiella pneumoniae and of KPC-encoding plasmids. In this study, we explored the population structure of KPC-encoding plasmids from the recent epidemics of KPC-producing K. pneumoniae (KPC-Kp) in Greece and Italy, the two major European endemic settings. Thirty-four non-replicate clinical strains of KPC-Kp representative of the early phases (2008-11) of the Greek (n = 22) and Italian (n = 12) epidemics were studied. Isolates were typed by MLST, and blaKPC-carrying plasmids were characterized by S1 profiling, PCR-based replicon typing and RFLP. Transfer experiments by conjugation or transformation were carried out with Escherichia coli recipients. Eleven plasmids, representative of all different restriction profiles, were completely sequenced. The representative Greek strains belonged to 14 sequence types (STs), with a predominance of ST258. The representative Italian strains belonged to three STs, with a predominance of clonal complex 258 (ST258, ST512). The 34 strains carried plasmids of variable size (78-166 kb), either with blaKPC-2 or blaKPC-3 gene embedded in a Tn4401a transposon. Plasmids from Greek strains were mostly of a single RFLP type (A) and resembled the archetypal pKpQIL KPC-encoding plasmid, while plasmids from Italian strains belonged to a more heterogeneous population, showing five RFLP profiles (A, C-F). Types A and C resembled pKpQIL or deletion derivatives thereof, while types D-F included plasmids with hybrid structures between pKpQIL, pKPN3 and pKPN101-IT. pKpQIL-like plasmids played a major role in the dissemination of blaKPC in Greece and Italy, but evolved with different dynamics in these endemic settings.


Does dynamical synchronization among neurons facilitate learning and enhance task performance?
Synchronization among groups of neurons is an interesting yet mysterious mechanism in the brain. We propose and demonstrate that the adjustable timing of neural activities can produce profound effect on learning and task implementation. On one hand, learning of more complex patterns becomes possible because of the enhanced capability of classification. On the other hand, implementation of a complex task is aided through active maintenance and control of multiple rules and items. This sheds light on the development of new intelligent system, as well as the cause of impaired learning and task performance in patients.


Fluorescence study of the effects of histone tyrosyl residues of DNA.
The fluorescence spectra of histone-DNA complexes at pH 7.0 were studied. These species showed fluorescence spectra broader than the characteristic histone spectrum, with the appearance of peaks at higher wavelengths. It is shown that the emission at higher wavelengths arises from the bases of DNA (specially from the A-T bases), when their hydrogen bonds are weakened or broken. These results corroborate those of other authors and it is postulated that tyrosine residues in histone form hydrogen bonds with DNA and/or stack with the bases of the nucleic acid.


Risk Factors and Outcomes From All-Terrain Vehicle Injuries Compared With Motor Vehicle Collisions in Children.
We compared risk factors and outcomes of children injured from all-terrain vehicle (ATV) injuries to those injured from motor vehicle collisions (MVC). We reviewed records of patients ≤18 years of age admitted to a trauma center with ATV- or MVC-related injuries between January 1, 2000, and December 31, 2015. Demographics were compared using logistic regression. Rates of injuries were compared using χ2 tests. Of 6293 patients, 1140 (18%) ATV and 5153 (82%) MVC events were identified. In multivariable analysis (adjusted odds ratio [aOR], 95% confidence interval [CI]), patients with ATV-related injuries occurred more at older age (≥12 years; aOR = 4.29, 95% CI = 3.20-5.77), in rural counties (aOR = 3.72, 95% CI = 2.62-5.28), in regions with lower median household income (aOR = 1.37, 95% CI = 1.03-1.83), and in the spring (aOR = 2.44, 95% CI = 1.87-3.18), and summer (aOR = 2.50, 95% CI = 1.93-3.25) compared with winter. ATV-related injuries occurred less frequently among females (aOR = 0.76, 95% CI = 0.65-0.89). Upper extremity injuries were associated with ATV-related injuries (P ≤ .001). Findings may facilitate identification of at-risk groups for targeted interventions.


The role of hair cell regeneration in an avian model of inner ear injury and repair from acoustic trauma.
The auditory system of young chicks (Gallus domesticus)is an important model for studying the structure and function of the inner ear. For over 20 years this model has gained interest because of the discovery that birds, and perhaps lower vertebrates in general, are capable of generating new hair cells to replace those lost to ototrauma, a capacity that is absent along the mammalian organ of Corti. Accompanying this remarkable capacity is the nearly complete restoration of auditory function to the chick peripheral ear. This article presents a review of findings on the toxic effect of exposure to extremely loud sound on the young chick ear, and the subsequent recovery from inner ear structural damage and accompanying recovery of auditory function. The evidence, surprisingly, suggests that the role of the regenerated hair cells in the latter may be minimal and that multiple other factors play more important roles. There is also a section on the unique problems encountered in using chicks as laboratory animal subjects in experiments designed to understand the consequences of acoustic trauma. The conclusion summarizes some of the issues that need to be addressed in future research.


Halothane-induced renal vasodilation.
Halothane-induced changes in renal function have generally been attributed to alterations in systemic hemodynamics, sympathetic tone, and various hormones. Studies were performed to determine whether halothane directly affects the kidney. Twenty-one canine kidneys were perfused in vitro utilizing hemodilution, pulsatile flow, and membrane oxygenation. Temperature and arterial blood-gas variables were controlled and mean and pulse pressures were maintained. Four experimental periods (I-IV)(each consisting of two 10-min sample collection periods) were conducted, with a 20-min "rest" period between succeeding experimental periods (elapsed time = 140 min). Responsiveness was assured by obtaining a normal response to furosemide, acetylcholine, or epinephrine after Period IV. In eight additional kidney preparations halothane was administered to achieve either a "low" (17 +/- 3 mg/100 ml) or "high" (35 +/- 5 mg/100 ml) concentration in Period II, the sequence reversed for Period III, and halothane eliminated by Period IV. Halothane produced marked increases in blood flow (21-26 per cent), total (203-267 per cent) and fractional (173-179 per cent) sodium excretion, osmolal clearance (62-111 per cent) and urinary volume (130-161 per cent). These changes were associated with a shift of microspheres from outer to inner cortex, and were completely reversible by eliminating the halothane. In the absence of external influences, halothane produces renal vasodilation and natriuresis. Direct tubular depression cannot be ruled out.


Immunohistochemical identification of androgen receptors in germ cell neoplasia.
The highest prevalence of testicular cancer occurs in young men with high androgen activity. The presence and distribution of androgen receptors (ARs) was therefore investigated in germ cell neoplasia, using two specific monoclonal antibodies. Tissue samples from 18 patients with seminoma and/or carcinoma-in-situ (CIS) of the testis were examined. An indirect immunohistochemical method with a biotin-streptavidin-peroxidase or an alkaline phosphatase detection system was used. 45% of seminoma samples and 42% of CIS samples were AR-positive with antibody AN 1-15. The values obtained using antibody F 39.4.1 were 44 and 40% respectively. Some differences in specificity between the two antibodies were observed. Unusual granular staining of germ cells in normal testes, also present in malignant germ cells, was noted when antibody F39.4.1 was used. The presence of AR protein immunoreactivity in neoplastic germ cells suggests that androgens may be involved in the pathogenesis of the disease.


Neuropsychiatric disease and Toxoplasma gondii infection.
Toxoplasma gondii infects approximately 30% of the world's population, but causes overt clinical symptoms in only a small proportion of people. In recent years, the ability of the parasite to manipulate the behaviour of infected mice and rats and alter personality attributes of humans has been reported. Furthermore, a number of studies have now suggested T. gondii infection as a risk factor for the development of schizophrenia and depression in humans. As T. gondii forms cysts that are located in various anatomical sites including the brain during a chronic infection, it is well placed anatomically to mediate these effects directly. The T. gondii genome is known to contain 2 aromatic amino acid hydroxylases that potentially could directly affect dopamine and/or serotonin biosynthesis. However, stimulation of the immune response has also recently been associated with mood and behavioural alterations in humans, and compounds designed to alter mood, such as fluoxetine, have been demonstrated to alter aspects of immune function. Herein, the evidence for T.-gondii-induced behavioural changes relevant to schizophrenia and depression is reviewed. Potential mechanisms responsible for these changes in behaviour including the role of tryptophan metabolism and the hypothalamic-pituitary-adrenal axis are discussed.


Protein misfolding and cellular stress: an overview.
Cell survival and death are complex matters. Too much survival may lead to cancer and too much cell death may result in tissue degeneration. In this chapter, we will first of all focus on the cellular survival mechanisms that promote correct folding and maintenance of protein function. These mechanisms include protein quality control (PQC) systems comprising molecular chaperones and intracellular proteases in the cytosol, endoplasmatic reticulum (ER) and in the mitochondria. In addition to the PQC systems, mechanisms elicited by misfolded proteins, known as unfolded protein responses (UPRs), including induction/activation of antioxidant systems are also present in the three compartments of the cell. Second, we will discuss the mechanisms by which misfolded proteins lead to the generation of oxidative stress in the form of reactive oxygen species (ROS) and reactive nitrogen species (RNS). These species are produced mainly from superoxide (O2-) generated in the mitochondrial respiratory chain and from nitrogen oxide (NO) produced by the mitochondrial nitrogen oxide synthetase (mtNOS). Third, the effects of oxidative stress will be discussed, both with respect to mitochondrial dynamics, i.e., fission and fusion, and the related elimination of dysfunctional mitochondria by cellular cleaning systems, i.e., mitophagy or mitoptosis, and related to the generation and cellular effects of oxidatively modified proteins, which closes a vicious cycle of protein misfolding and oxidative stress.


Density functional theory study of the hydrogen bond interaction between lactones, lactams, and methanol.
The structure and relative stability of methanol complexes with various cyclic ketones, lactones, lactams, and N-methyl lactams from three- to seven-membered rings have been investigated using the density functional theory method. The geometries, harmonic frequencies, and energies were calculated at the B3LYP/6-311+G(d,p) level. Three stable structures, cis-a, cis-b, and trans, with respect to the ring oxygen (nitrogen) atom, were found to be local minima of the potential energy surface. For lactones and N-methyl lactams, the most stable structure is trans; it is stabilized, as in cyclic ketones, through the conventional hydrogen bond (HB) interaction between the basic carbonyl oxygen and the acidic methanolic hydrogen and an unconventional HB interaction between the methanolic oxygen and the CH hydrogen, in the alpha position of the carbonyl group. For unsubstituted lactams, the cis-a structure, stabilized through a HB interaction between the NH group and the methanol oxygen in addition to the conventional HB interaction, is the most stable. The topological properties of the electron density ratify the existence of conventional (N,O-H. . .O) and unconventional (C-H. . .O) hydrogen bonding. A good correlation was found between the HB distances and the electron density at the HB critical point. The unsubstituted lactams yield more stable complexes with methanol than N-methyl lactams, lactones, and cyclic ketones. In the most stable complexes, both components behave simultaneously as a HB donor and as a HB acceptor.


Impact of Motivational Interviewing on Medication Adherence in Schizophrenia.
This literature review addresses the question of whether motivational interviewing (MI) is effective at improving medication adherence in patients with schizophrenia. The databases PsycINFO, OVID Medline, and PubMed were searched using the keywords "schizophrenia," "medication adherence," and one of the following: "motivational interviewing," "adherence therapy," or "compliance therapy." Relevant studies from the last ten years were included, resulting in six studies being included in this literature review. One study presented evidence for a direct relationship between motivational interviewing and medication adherence. Most studies did not support this relationship. Some studies found evidence for a relationship between motivational interviewing and other outcomes such as improved psychotic symptoms and decreased re-hospitalization rates. Motivational interviewing may be beneficial for some patients with schizophrenia but should not be considered a first line therapy. Clinicians not already using motivational interviewing in providing care to their patients with schizophrenia should not implement it for this population.