HLA class II DR and DQ genotypes and haplotypes associated with rheumatic fever among a clinically homogeneous patient population of Latvian children

The HLA system is being paid more and more attention because it is very significant in polymorphous immunological reactions. Several studies have suggested that genetic susceptibility to rheumatic fever (RF) and rheumatic heart disease (RHD) is linked to HLA class II alleles. We hypothesized that HLA class II associations within RHD may be more consistent if analysed amongst patients with a relatively homogeneous clinical outcome. A total of 70 RF patients under the age of 18 years were surveyed and analysed in Latvia. HLA genotyping of DQA1, DQB1 and DRB1 was performed using PCR with amplification with sequence-specific primers. We also used results from a previous study of DQB1 and DRB1 genotyping. In the RF patients, HLA class II DQA1*0401 was found more frequently compared to DQA1*0102. In the RF homogeneous patient groups, DQA1*0402 has the highest odds ratio. This is also the case in the multivalvular lesion (MVL) group, together with DQA1*0501 and DQA1*0301. In the chorea minor patients, DQA1*0201 was often found. Significant HLA DQA1 protective genotypes were not detected, although DQA1 genotypes *0103/*0201 and *0301/*0501 were found significantly and frequently. In the distribution of HLA DRB1/DQA1 genotypes, *07/*0201 and *01/*0501 were frequently detected; these also occurred significantly often in the MVL group. The genotype *07/*0201 was frequently found in Sydenhamn's chorea patients that had also acquired RHD, but DRB1*04/DQA1*0401 was often apparent in RF patients without RHD. In the distribution of HLA DQA1/DQB1 genotypes, both in RF patients and in the homogeneous patient groups, the least frequent were *0102/*0602-8. The genotype DQA1*0501 with the DQB1 risk allele *0301 was often found in the MVL group. The genotype *0301/*0401-2 was frequently found in the RF and Sydenhamn's chorea patient groups. The haplotype *07-*0201-*0302 was frequently found in RF and homogeneous patient groups, including the MVL group. In addition, haplotypes *04-*0401-*0301 and *04-*0301-*0401-2 were frequent amongst patients with Sydenhamn's chorea. The protective alleles DQA1*0102 and DQB1*0602-8 in the haplotype DRB1*15 were less frequently found in RF patients. The results of the present study support our hypothesis and indicate that certain HLA class II haplotypes are associated with risk for or protection against RHD and that these associations are more evident in patients in clinically homogeneous groups.     

The reliability and validity of short-distance sprint performance assessed on a nonmotorized treadmill

This study examined the interday and intraday reliabilities and validities of various sprint performance variables on a nonmotorized treadmill (NMT) over distances of 10, 20, and 30 m. After habituation, 12 male team-sport players performed 3 sprints on the NMT on 2 separate days and an assessment of overground running performance, separated by 24 hours. Measurements included sprint times, mean and peak sprint speeds, and step length and frequency. Data analysis revealed no significant mean differences (p > 0.05) between NMT variables recorded on the same day or between days. Ratio limits of agreement indicated that the best levels of agreement were in 20-m (1.02 ×/÷ 1.09) and 30-m (1.02 ×/÷ 1.07) sprint times, peak (1.00 ×/÷ 1.06) and mean (0.99 ×/÷ 1.07) running speed, and step length (0.99 ×/÷ 1.09) and frequency (1.01 ×/÷ 1.06). The poorest agreement was observed for time to peak running speed (1.10 ×/÷ 1.47). These reliability statements were reinforced by coefficients of variation being <5% for all the variables except time to peak running speed (11%). Significant differences (p < 0.05) were observed between NMT and overground sprint times across all distances, with times being lower (faster) by approximately 25-30% overground. The correlations between NMT and overground variables were generally modest (0.44-0.67), and optimal for time to cover 30 m on day 2. Our data support NMT ergometry as a reliable tool for most of the sprint performance variables measured and reveal that the fastest 30-m overground sprinters were likely to be identifiable via NMT ergometry.     

Immaturity of the oculomotor saccade and vergence interaction in dyslexic children: evidence from a reading and visual search study

Studies comparing binocular eye movements during reading and visual search in dyslexic children are, at our knowledge, inexistent. In the present study we examined ocular motor characteristics in dyslexic children versus two groups of non dyslexic children with chronological/reading age-matched. Binocular eye movements were recorded by an infrared system (mobileEBT®, e(ye)BRAIN) in twelve dyslexic children (mean age 11 years old) and a group of chronological age-matched (N = 9) and reading age-matched (N = 10) non dyslexic children. Two visual tasks were used: text reading and visual search. Independently of the task, the ocular motor behavior in dyslexic children is similar to those reported in reading age-matched non dyslexic children: many and longer fixations as well as poor quality of binocular coordination during and after the saccades. In contrast, chronological age-matched non dyslexic children showed a small number of fixations and short duration of fixations in reading task with respect to visual search task; furthermore their saccades were well yoked in both tasks. The atypical eye movement''s patterns observed in dyslexic children suggest a deficiency in the visual attentional processing as well as an immaturity of the ocular motor saccade and vergence systems interaction.     

A statistical analysis of prescreening alarms in a population of normal and abnormal gynecologic specimens

A multidimensional slit-scan flow system has been developed to serve as an automated prescreening instrument for gynecological cytology. Specimens are classified abnormal based on the number of cells having elevated nuclear fluorescence (alarms). An alarm region in a bivariate histogram of nuclear fluorescence versus nuclear-to-cell-diameter ratio is defined. Alarm region probability arrays are calculated to estimate the probability that an alarm falling in a particular bin of the alarm region is either from a normal or an abnormal specimen. From these arrays, a weighted alarm index is generated. In addition, summary indices are derived that measure how the distribution of alarms in each specimen compares with the average distributions for the normal and abnormal specimen populations. These indices together with current features are evaluated with respect to their utility in specimen classification using a nonparametric classification technique known as recursive partitioning. Resulting classification trees are presented that suggest information in the distribution of alarms in the bivariate histogram. In addition, they validate the features and rules currently used for specimen classification. Recursive partitioning appears to be useful for multivariate classification and is seen as a promising technique for other applications.     

Stress and dental asymmetry in a population of Japanese children

We studied the significance of the magnitude of fluctuating dental asymmetry in 489 Japanese children by regression analysis. The search was for the predictability of asymmetry from levels of five factors assumed to be relevant parameters of prenatal stress. The five factors were derived by principal components analysis to simplify the interrelationships between birth weight, gestational age, maternal age, parity, sex, year of birth, socioeconomic status, and F, the coefficient of inbreeding. Only the regression of asymmetry on a factor representing a secular effect related to sex ratio was statistically significant; however, the relationship was too small to be biologically meaningful. The significance of individual asymmetry is thus equivocal, and this is discussed in terms of the meaning of asymmetry vis à vis overall fitness and developmental homeostasis. We conclude that experimental research will be necessary to elucidate not only the determinants of dental asymmetry but the relationship between these determinants and mortality and morbidity.     

Neural Activity in the Macaque Putamen Associated with Saccades and Behavioral Outcome

It is now widely accepted that the basal ganglia nuclei form segregated, parallel loops with neocortical areas. The prevalent view is that the putamen is part of the motor loop, which receives inputs from sensorimotor areas, whereas the caudate, which receives inputs from frontal cortical eye fields and projects via the substantia nigra pars reticulata to the superior colliculus, belongs to the oculomotor loop. Tracer studies in monkeys and functional neuroimaging studies in human subjects, however, also suggest a potential role for the putamen in oculomotor control. To investigate the role of the putamen in saccadic eye movements, we recorded single neuron activity in the caudal putamen of two rhesus monkeys while they alternated between short blocks of pro- and anti-saccades. In each trial, the instruction cue was provided after the onset of the peripheral stimulus, thus the monkeys could either generate an immediate response to the stimulus based on the internal representation of the rule from the previous trial, or alternatively, could await the visual rule-instruction cue to guide their saccadic response. We found that a subset of putamen neurons showed saccade-related activity, that the preparatory mode (internally- versus externally-cued) influenced the expression of task-selectivity in roughly one third of the task-modulated neurons, and further that a large proportion of neurons encoded the outcome of the saccade. These results suggest that the caudal putamen may be part of the neural network for goal-directed saccades, wherein the monitoring of saccadic eye movements, context and performance feedback may be processed together to ensure optimal behavioural performance and outcomes are achieved during ongoing behaviour.     

Diagnostic value of salivary cortisol in children with abnormal adrenal cortex functions

AIMS: It has been shown that the free cortisol level in saliva may reflect plasma free cortisol. The measurement of cortisol in saliva is a simple method, and as such it is important in the pediatric age group. In this research, the diagnostic value of measurement of salivary cortisol (SC) measurement was examined in adrenal insufficiency (AI). METHODS: Fifty-one patients, mean age 10.8 +/- 4.29, who were investigated for possible AI, were included. Basal cortisol levels were below 18 microg/dl. Adrenal function was determined by low-dose ACTH test. During the test, samples for SC were obtained simultaneously with serum samples (at 0-10-20-30-40 min). RESULTS: Mean basal serum cortisol level was 8.21 +/- 4.10 microg/dl (mean +/- SD). Basal SC was correlated to basal serum cortisol (r = 0.64, p < 0.001). A cut-off of 0.94 microg/dl for SC differentiated adrenal insufficient subjects from normals with a sensitivity and specificity of 80 and 77%, respectively. A peak SC less than 0.62 microg/dl defined AI with a specificity of 100%; however, sensitivity was 44%. CONCLUSION: Measurement of SC may be used in the evaluation of AI. It is well-correlated to serum cortisol. Peak SC in low-dose ACTH test can be used to differentiate patients with AI in the initial evaluation of individuals with suspected AI.     

Diminished foraging performance of a mutant zebrafish with reduced population of ultraviolet cones

Ultraviolet (UV) cones are photoreceptors that sense light in the range 300–450 nm and are found in the retinas of non-mammalian vertebrates and small mammals. Despite their widespread presence across taxa, the functions that these cones exert in the lives of animals remain largely unknown. In this study, I used the zebrafish lor (lots of rods) mutant, characterized by a diminished UV cone population compared to that of wild-type zebrafish, to test whether its foraging performance differed from that of the wild-type (control). The mean location distance and angle (variables that are reliable indicators of foraging performance) at which control fish detected zooplankton prey were, on average, 24 and 90% greater than corresponding measures for lor fish. Such inferior foraging performance of the mutant could be explained by reduced contrast perception of the prey, resulting from the diminished population of UV cones and associated sensitivity. Thus, UV cones enhance the foraging performance of zebrafish, a crucial ecological function that may explain why small zooplanktivorous fishes retain UV cones throughout their lives.     

Association of selected SNP with carcass and taste panel assessed meat quality traits in a commercial population of Aberdeen Angus-sired beef cattle

Background

The purpose of this study was to evaluate the effects of eight single nucleotide polymorphisms (SNP), previously associated with meat and milk quality traits in cattle, in a population of 443 commercial Aberdeen Angus-cross beef cattle. The eight SNP, which were located within five genes: μ-calpain (CAPN1), calpastatin (CAST), leptin (LEP), growth hormone receptor (GHR) and acylCoA:diacylglycerol acyltransferase 1 (DGAT1), are included in various commercial tests for tenderness, fatness, carcass composition and milk yield/quality.

Methods

A total of 27 traits were examined, 19 relating to carcass quality, such as carcass weight and fatness, one mechanical measure of tenderness, and the remaining seven were sensory traits, such as flavour and tenderness, assessed by a taste panel.

Results

An SNP in the CAPN1 gene, CAPN316, was significantly associated with tenderness measured by both the tenderometer and the taste panel as well as the weight of the hindquarter, where animals inheriting the CC genotype had more tender meat and heavier hindquarters. An SNP in the leptin gene, UASMS2, significantly affected overall liking, where animals with the TT genotype were assigned higher scores by the panellists. The SNP in the GHR gene was significantly associated with odour, where animals inheriting the AA genotype produced steaks with an intense odour when compared with the other genotypes. Finally, the SNP in the DGAT1 gene was associated with sirloin weight after maturation and fat depth surrounding the sirloin, with animals inheriting the AA genotype having heavier sirloins and more fat.

Conclusion

The results of this study confirm some previously documented associations. Furthermore, novel associations have been identified which, following validation in other populations, could be incorporated into breeding programmes to improve meat quality.     

Encapsulation of myoglobin with a mesoporous silicate results in new capabilities

A metmyoglobin (Fe3+), an oxidized form of myoglobin (Fe2+), was confined in nanospaces of about 4 nm in diameter in mesoporous silica (FSM; folded-sheet mesoporous material), forming a metmyoglobin (Fe3+)-FSM nanoconjugate. The spectral characteristics of metmyoglobin (Fe3+)- and myoglobin (Fe2+)-FSM show an absorption curve quite similar to that of native metmyoglobin, indicating that myoglobin retains its higher-order structure in the pores of FSM. The metmyoglobin (Fe3+)-FSM conjugate had not only a peroxidase-like activity in the presence of hydrogen peroxide (a hydrogen acceptor) and 2,2-azino-bis(3-ethylbenzothiazoline)-6-sulfomic acid (ABTS) or guaiacol (a hydrogen donor) but also an advanced molecular recognition ability enabling it to distinguish between ABTS and guaiacol. Furthermore, the metmyoglobin (Fe3+)-FSM showed the peroxidase-like activity even in an organic media using benzoyl peroxide as the hydrogen acceptor and leucocrystal violet as the hydrogen donor. The simple immobilization of metmyoglobin (Fe3+) into FSM results in enhanced catalytic activity in organic media compared to that of native metmyoglobin (Fe3+).     

Seasonality of dizziness and vertigo in a tropical region

Vertigo and dizziness are among the most common medical complaints in the emergency room, and are associated with a considerable personal and health care burden. Scarce and conflicting reports indicate those symptoms may present a seasonal distribution. This study aimed at investigating the existence of a seasonal distribution of vertigo/dizziness in a tropical region, and the correlations of these findings with climatic variables. The charts of all patients consecutively admitted between 2009 and 2012 in the emergency room of a Brazilian general hospital were reviewed. A total of 4920 cases containing these terms were sorted from a sample of 276?076 emergency records. Seasonality was assessed using Cosinor Analysis. Pearson's correlations were performed between the incidence of consultations, considering separately dizziness and vertigo and each of the predictor climatic variables of that index month. Significant seasonal patterns were observed for dizziness and vertigo in the emergency room. Vertigo was more frequent in late winter–spring, negatively correlating to humidity (r?=??0.374; p?=?0.013) and rainfall (r?=??0.334; p?=?0.020). Dizziness peaked on summer months, and positively correlated to average temperatures (r?=?0.520; p?<?0.001) and rainfall (r?=?0.297; p?=?0.040), but negatively to atmospheric pressure (r?=??0.424; p?=?0.003). The different seasonal patterns evidenced for dizziness and vertigo indicate possible distinct underlying mechanisms of how seasons may influence the occurrence of those symptoms.     

PEGylation of microspheres generates a heterogeneous population of particles with differential surface characteristics and biological performance

Surface PEGylation of polystyrene microspheres with methoxy-poly(ethylene glycol)-5000 (mPEG-5000) generated a heterogeneous population of entities that differed in surface characteristics and in vitro biological performance (phagocytosis and complement activation). Surface heterogeneity was determined by hydrophobic interaction chromatography, measurements of particle electrophoretic mobility in a defined field and adlayer thickness of the projected mPEG chains. The particle population separation by hydrophobic interaction chromatography demonstrated a remarkable linear relationship between the particle zeta potential and phagocytosis by J774 A1 macrophage-like cells. Microsphere populations bearing a predominant surface of mPEG molecules as high-density mushroom-brush intermediate and/or brush configuration were most resistant to phagocytosis and activated the human complement system poorly. Conversely, those populations with predominant surface mPEGs in a mushroom regime were potent activators of the complement system and were prone to phagocytosis. Therefore, surface heterogeneity explains why a fraction of intravenously injected 'long-circulating' nanoparticles is cleared rapidly by macrophages of the reticuloendothelial system. Hydrophobic interaction chromatography can readily assess the extent of surface heterogeneity of PEGylated particulate drug delivery systems and pre-select particles with optimal retention times in the blood. These observations may also be relevant with respect to successful surface camouflaging of cells, drug depots and implantable devices.     

Effects of cardiopulmonary bypass surgery on coronary flow in children assessed with transthoracic Doppler echocardiography

Perturbation of coronary blood flow (CF) is an important contributor to myocardium-related complications. The study was primarily designed to assess the impact of cardiopulmonary bypass (CPB) surgery on CF by aid of transthoracic Doppler echocardiography. Changes in CF after off-pump coarctation surgery were also studied. All ultrasounds were performed before and 5 +/- 1 days after surgery. Eighteen children underwent CPB surgery of ventricular left-to-right shunts at the mean age of 6 mo, while off-pump surgery (aortic coarctectomy) was undertaken at the mean age of 10 days in 12 children. After CPB surgery, both left anterior descending coronary artery mean diameter and basal CF increased from 1.7 +/- 0.3 to 2.1 +/- 0.4 mm (P = 0.001) and 27 +/- 10 to 47 +/- 15 ml/min (P = 0.0001), respectively. These two coronary variables decreased after off-pump coarctectomy: left anterior descending coronary artery mean diameter from 1.8 +/- 0.1 to 1.7 +/- 0.1 mm (P = 0.06), and CF from 44 +/- 12 to 25 +/- 8 ml/min (P = 0.001). The findings are in keeping with the hypothesis that the previously reported impairment of coronary flow reserve after CPB surgery could be due to increase in basal coronary flow after CPB. Off-pump coarctectomy seems to have little impact on CF, as the postsurgical decline in flow in these patients seems to relate to the reduction in cardiac pressure afterload.     

Wall stress misrepresents afterload in children and young adults with abnormal left ventricular geometry.

Wall stress, although commonly used as an index of afterload, fails to take into account forces generated within the wall of the left ventricle (LV) that oppose systolic fiber shortening. Wall stress may, therefore, misrepresent fiber stress, the force resisting fiber shortening, particularly in the presence of an abnormal LV thickness-to-dimension ratio (h/D). M-mode LV echocardiograms were obtained from 207 patients with a wide range of values for LV mass and/or h/D. Diagnoses were valvar aortic stenosis, coarctation repair, anthracycline treated, and severe aortic and/or mitral regurgitation. End-systolic wall stress (WS(es)) and fiber stress (FS(es)) were expressed as age-corrected Z scores relative to a normal population. The difference between WS(es) and FS(es) was extreme when h/D was elevated or reduced [WS(es) Z score - FS(es) Z score = 0.14 x (h/D)(-1.47) - 2.13; r = 0.78, P < 0.001], with WS(es) underestimating FS(es) when h/D was increased and overestimating FS(es) when h/D was decreased. Analyses of myocardial mechanics based on wall stress have limited validity in patients with abnormal ventricular geometry.     

Cryptic changes in the genetic structure of a highly clonal coral population and the relationship with ecological performance

Elkhorn coral, Acropora palmata, relies heavily on clonal propagation and often displays low genotypic (clonal) diversity. Populations in the Florida Keys experienced rapid declines in tissue cover between 2004 and 2006, largely due to hurricanes and disease, but remained stable from 2006 to 2010. All elkhorn colonies in 150 m² permanent study plots were genotyped in 2006 (n = 15 plots) and 2010 (n = 24 plots), and plots sampled in both years were examined for changes in allelic and genotypic diversity during this period of stable ecological abundance. Overall, genetic diversity of Florida plots was low and declined further over the 4-yr period; seven of the 36 original genets and two of 67 alleles (among five microsatellite loci) were lost completely from the sampled population, and an additional 15 alleles were lost from individual reefs. In 2010, Florida plots (~19 colonies) contained an average of 2.2 ± 1.38 (mean ± SD) genets with a significant negative correlation between colony abundance and genotypic diversity. When scaled to total tissue abundance, genotypic diversity is even lower, with 43 % of genets below the size of sexual maturity. We examined the hypothesized positive relationship of local genotypic diversity with ecological performance measures. In Florida plots (n = 15), genotypic diversity was not significantly correlated with tissue loss associated with chronic predation, nor with acute disease and storm-fragmentation events, though this relationship may be obscured by the low range of observed diversity and potential confounding with abundance. When more diverse plots in Curaçao (n = 9) were examined, genotypic diversity was not significantly correlated with resistance during an acute storm disturbance or rate of recovery following disturbance. Cryptic loss of genetic diversity occurred in the apparently stable Florida population and confirms that stable or even increasing abundance does not necessarily indicate genetic stability.     

Genetic disorders in children and young adults: a population study.

The data base of an ongoing population-based registry with multiple sources of ascertainment was used to estimate the present population load from genetic disease in more than 1 million consecutive live births. It was found that, before approximately age 25 years, greater than or equal to 53/1,000 live-born individuals can be expected to have diseases with an important genetic component. This total was composed of single-gene disorders (3.6/1,000), consisting of autosomal dominant (1.4/1,000), autosomal recessive (1.7/1,000), and X-linked recessive disorders (0.5/1,000). Chromosomal anomalies accounted for 1.8/1,000, multifactorial disorders (including those present at birth and those of onset before age 25 years) accounted for 46.4/1,000, and cases of genetic etiology in which the precise mechanism was not identified accounted for 1.2/1,000. Previous studies have usually considered all congenital anomalies (ICD 740-759) as part of the genetic load, but only those judged to fit into one of the above categories were included in the present study. Data for congenital anomalies are therefore also presented separately, to facilitate comparison with earlier studies. If all congenital anomalies are considered as part of the genetic load, then greater than or equal to 79/1,000 live-born individuals have been identified as having one or other genetic disorder before approximately age 25 years. These new data represent a better estimate of the genetic load in the population than do previous studies.     

Ocular-Motor Profile and Effects of Memantine in a Familial Form of Adult Cerebellar Ataxia with Slow Saccades and Square Wave Saccadic Intrusions

Fixation instability due to saccadic intrusions is a feature of autosomal recessive spinocerebellar ataxias, and includes square wave intrusions (SWI) and macrosaccadic oscillations (MSO). A recent report suggested that the non-competitive antagonist of NMDA receptors, memantine, could decrease MSO and improve fixation in patients with spinocerebellar ataxia with saccadic intrusions (SCASI). We similarly tested two sisters, respectively of 58 and 60 years, with an unrecognized form of recessive, adult-onset cerebellar ataxia, peripheral neuropathy and slow saccades, who showed prominent SWI and also complained with difficulty in reading. We tested horizontal visually guided saccades (10°–18°) and three minutes of steady fixation in each patient and in thirty healthy controls. Both patients showed a significant reduction of peak and mean velocity compared with control subjects. Large SWI interrupting steady fixation were prominent during steady fixation and especially following visually guided saccades. Eye movements were recorded before and during the treatment with memantine, 20 mg/daily for 6 months. The treatment with memantine reduced both the magnitude and frequency of SWI (the former significantly), but did not modified neurological conditions or saccade parameters. Thus, our report suggests that memantine may have some general suppressive effect on saccadic intrusions, including both SWI and MSO, thereby restoring the capacity of reading and visual attention in these and in other recessive forms of ataxia, including Friedreich’s, in which saccadic intrusions are prominent.     

HLA class II associations with rheumatic heart disease among clinically homogeneous patients in children in Latvia

Genetic control of immune reactions has a major role in the development of rheumatic heart disease (RHD) and differs between patients with rheumatic fever (RF). Some authors think the risk of acquiring RHD is associated with the HLA class II DR and DQ loci, but other views exist, due to the various HLA-typing methods and ways of grouping cases. Our goal was to determine the relations between HLA class II alleles and risk of or protection from RF in patients with relatively homogeneous clinical manifestations. A total of 70 RF patients under the age of 18 years were surveyed in Latvia. HLA genotyping of DRB1*01 to DRB1*18 and DQB1*0201-202, *0301-305, *0401-402, *0501-504, and *0601-608 was performed using polymerase chain reaction sequence-specific primers. Data for a control group of 100 healthy individuals typed for HLA by the same method were available from the databank of the Immunology Institute of Latvia. Of the RF patients, 47 had RHD and 8 had Sydenham's chorea. We concluded that HLA class II DRB1*07-DQB1*0401-2 and DRB1*07-DQB1*0302 could be the risk alleles and HLA class II DRB1*06 and DQB1*0602-8, the protective ones. Patients with mitral valve regurgitation more often had DRB1*07 and DQB1*0401-2, and patients with multivalvular lesions more often had DRB1*07 and DQB1*0302. In Sydenham's chorea patients, the DQB1*0401-2 allele was more frequent. Genotyping control showed a high risk of RF and RHD in patients with DRB1*01-DQB1*0301-DRB1*07-DQB1*0302 and DRB1*15-DQB1*0302-DRB1*07-DQB1*0303.