Variability of hemagglutinin-neuraminidase and nucleocapsid protein of vaccine and wild-type mumps virus strains.

The mumps virus (MuV) molecular evolution is characterized by the co-circulation of numerous distinct strains. Standardized phylogenetic analyses based on the nucleotide sequences of the SH gene are important for mumps surveillance, but lack the information regarding antigenic properties. So far, the location of antigenic epitopes has been determined for two MuV proteins, the hemagglutinin-neuraminidase (HN) and the nucleocapsid (N) protein. We performed multiple sequence comparisons of putative HN and N protein sequences in order to describe their diversity and plasticity, and to determine the level of similarity between vaccine and wild-type strains. The results of full-length HN or N protein phylogeny showed that MuV strains form a number of differing clades which are in concordance with grouping obtained by standard MuV genotyping. When vaccine strains are compared to all wild-type strains, the highest mean percentage of amino acid differences in both HN and N protein analysis was found for Jeryl Lynn 5 and Jeryl Lynn 2 strains while the lowest value was obtained for Leningrad-3 and L-Zagreb strains. When only 3 antigenic regions of the HN protein, comprising 45 amino acids in total, were investigated, the diversity is considerably diminished: 51.5% of all putative HN proteins show identical sequences (including those of vaccine strains L-Zagreb, Leningrad-3, Hoshino and Urabe). Another 26.5% proteins (including Miyahara vaccine strain) differ in only one amino acid, while the others differ in two to five amino acids from the most common sequence. Jeryl Lynn 2 and Jeryl Lynn 5 strains differ in four amino acids each. N protein antigenic sites have been mapped within its hypervariable C-terminus. Our results indicate that there might be genotype-specific amino acids residing in this antigenic region. The results of our study present the background information for investigations of MuV heterogeneity and antigenic diversity.     

Bidirectional effects of benzodiazepine binding site ligands in the passive avoidance task: differential antagonism by flumazenil and beta-CCt

Recent research on genetically modified mice has attributed the amnesic effect of benzodiazepines mainly to the alpha1-containing GABA(A) receptor subtypes. The pharmacological approach, using subtype selective ligands, is needed to complement genetic studies. We tested the effects of the non-selective antagonist flumazenil (0-20.0 mg/kg), the preferential alpha1-subunit selective antagonist beta-carboline-3-carboxylate-t-butyl ester (beta-CCt) (0-30.0 mg/kg), the non-selective agonist midazolam (0-2.0 mg/kg), the preferential alpha1-subunit selective agonist zolpidem (0-3.0 mg/kg), and the non-selective inverse agonist methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) (0-2.0 mg/kg) in the one-trial step-through passive avoidance task in rats. The compounds were administered intraperitoneally, before the acquisition test. Flumazenil and beta-CCt did not affect retention performance. Midazolam and zolpidem induced amnesia in a dose-dependent manner. The complete reversal of amnesia was unattainable. The effects of zolpidem were significantly attenuated by the both, flumazenil (10.0 mg/kg) and beta-CCt (30.0 mg/kg); by contrast, only flumazenil was considerably effective when combined with midazolam. DMCM exerted promnesic effects at 0.2mg/kg, in an inverted U-shape manner. Both antagonists tended to abolish this action. The results indicate that some other alpha-subunit(s), in addition to the alpha1-subunit, contribute to the amnesic actions of non-selective benzodiazepine site agonists in the passive avoidance task. On the other hand, a significant part of the DMCM-induced promnesic effect could involve the alpha1-subunit and/or other putative beta-CCt-sensitive binding site(s).     

Ulcerative colitis indications and timing for surgery

Surgery continues to have a major role in the management of ulcerative colitis because it may save the patient's life, eliminate the long-term risk of cancer, and most important, abolish the disease. Treatment of ulcerative colitis still remains the challenge despite growing knowledge about the disease, advances in medical treatment and surgical techniques. Indications and optimal timing for surgery are the mainstays of good outcome and are as important as the quality of medical therapy and surgery. Ulcerative colitis is a complex disease where medical and surgical treatment frequently overlap and clinical decision making should be in hands of well trained and experienced team consisting of surgeon, gastroenterologist, radiologist and pathologist. Recently developed drugs, with high potential in the treatment of severe attacks of ulcerative colitis brought some changes in therapy and indications for surgical treatment. Although as many as half of patients with inflammatory bowel disease require at least one surgical procedure to address complications derived from their disease, the decision in favor of a surgical approach and its timing is rarely an easy one.     

Early results of subvastus versus medial parapatellar approach in primary total knee arthroplasty

Introduction To evaluate the clinical and radiographic results immediately after total knee arthroplasty, we compared the parapatellar and subvastus approach.Materials and methods Fifty-two patients with osteoarthritis were randomly assigned to two groups. The measurement was based on clinical and radiographic features.Results There was a significant difference in passive range of motion. Patients in the subvastus approach group revealed a full knee extension and flexion of 90° significantly earlier than those in the parapatellar group. However, on the day of discharge, both groups were comparable. Radiological assessment revealed analogous results in both groups. Correction of varus or valgus deformity was required in 48 patients.Conclusion Regardless of the surgical approach, the anteroposterior tibial femoral angle improved significantly in both groups. Concerning pain, operation time, blood loss, blood substitution and complications, no major differences could be seen.     

Acupuncture conversion of fetal breech presentation

AIM: The aim of this study was to assess the value of acupuncture (AP) in the conversion of fetal breech presentation into vertex presentation. PATIENTS AND METHODS: A randomized prospective controlled clinical study included 67 pregnant women with fetal breech presentation: 34 women with singleton pregnancies treated with manual AP (urinary bladder 67, Zhiyin) and a control group which included 33 women with singleton pregnancies without AP treatment. The AP treatment lasted 30 min a day, and was conducted during and after 34 weeks of pregnancy with simultaneous cardiotocography. RESULTS: The success rate of the AP correction of fetal breech presentation is 76.4% (26 women), and spontaneous conversion without AP in vertex presentation is observed in 15 women (45.4%; p<0.001). CONCLUSIONS: We believe that AP correction of fetal malpresentation is a relatively simple, efficacious and inexpensive method associated with a lower percentage of operatively completed deliveries, which definitely reflects in improved parameters of vital and perinatal statistics.     

Modulation of electroencephalographic responses to transcranial magnetic stimulation: evidence for changes in cortical excitability related to movement

Transcranial magnetic stimulation (TMS) and multichannel electroencephalography (EEG) were used for the investigation of cortical excitability preceding voluntary movement in human subjects. The study showed the practical value of the combined TMS-EEG approach in differentiating between cortical and spinal-cord mechanisms, which is difficult with conventional electromyographic measures alone. TMS induced a pronounced negativity (N100) lasting for 150-200 ms, with the amplitude maximum in the stimulated hemisphere. When TMS was applied just before the onset of the visually triggered movement, N100 was markedly attenuated, although motor evoked potentials (MEPs) became larger. We suggest that the N100 component represents an inhibitory response following TMS. This interpretation is in agreement with intracellular recordings in animals, paired-pulse TMS studies and experiments showing increased premovement excitability on the basis of MEPs. N100 was not affected only by the subsequent movement, but also by the switching from rest to the motor-task condition, which caused a slight attenuation of the N100 component; no changes, however, were found in the amplitude of MEPs, suggesting that modified excitability did not affect the output of the corticospinal pyramidal cells. By contrast to MEPs, N100 was modulated also by the presentation of the visual stimulus alone, i.e. when no movement was required. This attenuation suggests that even in a rest condition visual stimuli have an access to the sensorimotor regions of the cortex, most probably through ascending arousal brain systems.     

Beckwith Wiedemann syndrome: A population-based study on prevalence,prenatal diagnosis,associated anomalies and survival in Europe

Beckwith Wiedemann syndrome is a complex developmental disorder characterized by somatic overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycemia, and predisposition to embryonal tumors. We present epidemiological and clinical aspects of patients with Beckwith Wiedemann syndrome diagnosed prenatally or in the early years of life, using data from EUROCAT (European Surveillance of Congenital Anomalies) registries. The study population consisted of 371 cases identified between January 1990 and December 2015 in 34 registries from 16 European countries. There were 15 (4.0%) terminations of pregnancy after prenatal detection of severe anomaly/anomalies, 10 fetal deaths (2.7%), and 346 (93.3%) live-births. Twelve (3.6%) of the 330 live-births with available information on survival died in the first week of life, of those eleven (91.6%) were preterm. First-year survival rate was 90.9%. Prematurity was present in 40.6% of males and 33.9% of females. Macrosomia was found in 49.2% and 43.3% of preterm males and females, respectively. Of term newborns, 41.1% of males and 24% of females were macrosomic. Out of 353 cases with known time of diagnosis, 39.9% were suspected prenatally, 36.3% at birth, 7.6% were diagnosed in the first week of life, and 16.2% in the first year of life. The mean gestational age at prenatal diagnosis by obstetric ultrasound was 19.8?±?6.2 (11–39) gestational weeks. The mean prenatal diagnosis of cases where parents opted for termination of pregnancy was 15.3?±?2.4 (11–22) gestational weeks, and the mean gestational age at termination was 19.3?±?4.1 (13–26) gestational weeks. The prenatal detection rate was 64.1% (141/220) with no significant change over time. There were 12.7% of familial cases. The study confirmed the association of assisted reproductive technologies with Beckwith Wiedemann syndrome, as 7.2% (13/181) of patients were conceived by one of the methods of assisted reproductive technologies, which was three times higher compared to the general population of the countries included in the study. Twin pregnancies of undetermined zygosity were recorded in 5.7% (21/365) cases, and were on average three to four times more common than in European countries that participated in the study. The estimated mean prevalence of classical Beckwith Wiedemann syndrome in Europe was 3.8 per 100,000 births or 1:26,000 births.     

Dental archforms in dentoalveolar Class I,II and III

Objective:To test the hypothesis that no differences exist in dental arch dimensions between dentoalveolar Classes I, II, and III, and between male and female subjects, as measured on virtual three-dimensional (3D) models.Materials and Methods:Samples included randomly selected plaster dental casts of 137 white patients (43 Class I, 50 Class II, and 44 Class III) from the Department of Orthodontics, School of Dental Medicine, University of Zagreb, Croatia. Dental models were scanned and digitized using ATOS II SO (“Small Objects”) scanning technology (GOM mbH, Braunschweig, Germany). Eight linear and two proportional measurements were calculated for both upper and lower dental arches.Results:In men, a significant difference in the upper dental arch was present in the incisor region, and in the lower dental arch, differences were found in intercanine and intermolar widths (P < .05). Significant differences were noted between male groups in the upper molar depth dimension (P  =  .022) and in the lower molar and canine depth dimensions (P < .05). Class III males had the greatest lower molar and canine width/depth ratios and the smallest lower canine depth/molar depth ratio. Class III women had wider and shorter mandibular arches when compared with Class I and Class II females.Conclusion:The hypothesis was rejected. The dimensions of the dental arches are related to gender and to dentoalveolar class. Class I and II subjects have similar dimensions of maxillary dental arch, but Class II subjects have a transverse deficit in the mandible. In Class III subjects, the maxillary dental arch is insufficient in transverse and sagittal dimensions, and the mandibular arch dominates in the transverse but not in the sagittal dimension.     

Parallel input makes the brain run faster

In serial sensory processing, information flows from the thalamus via primary sensory cortices to higher-order association areas. However, association cortices also receive, albeit weak, direct thalamocortical sensory inputs of unknown function. For example, while information proceeds from primary (SI) to secondary (SII) somatosensory cortex in a serial fashion, both areas are known to receive direct thalamocortical sensory input. The present study examines the potential roles of such parallel input arrangements. The subjects were presented with median nerve somatosensory stimuli with the instruction to respond with the contralateral hand. The locations and time courses of the activated brain areas were first identified with magnetoencephalography (MEG). In a subsequent session, these brain areas were modulated with single-pulse transcranial magnetic stimulation (TMS) at 15-210 ms after the somatosensory stimulus while electroencephalography (EEG) was recorded. TMS pulses at 15-40 ms post-stimulus significantly speeded up reaction times and somatosensory-evoked responses, with largest facilitatory effects when the TMS pulse was given to contralateral SII at about 20 ms. To explain the results, we propose that the early somatosensory-evoked physiological SII activation exerts an SII-->SI influence that facilitates the reciprocal SI-->SII pathway - with TMS to SII we apparently amplified this mechanism. The results suggest that the human brain may utilize parallel inputs to facilitate long-distance cortico-cortical connections, resulting in accelerated processing and speeded reaction times. This arrangement could also allow very early top-down modulation of the bottom-up stream of sensory information.