Overt visual attention and between-limb asynchrony for bimanual reaching movements.

Although synchrony between the limbs is an often-cited feature of bimanual coordination, recent studies have also highlighted the small asynchronies that can occur. The visuo-motor demands of any bimanual task are considered central to the emergence of asynchrony, but the relationship between the two remains largely unexplored. This study aimed to address this issue. Hand and eye movements were measured in 19 participants, while they made either unimanual or bimanual reach-to-point (aiming) movements to targets presented on a touchscreen. Bimanual movements were either congruent (same-sized targets) or incongruent (different-sized targets). Resulting hand data showed many of the typical patterns of movement previously reported. While temporal coupling between the limbs remained largely evident for bimanual movements, small between-limb asynchronies were apparent and demonstrated clear associations with the competing precision requirements of the targets and related visual attention. Participants mainly directed their gaze towards the more difficult target with corresponding reaching movements demonstrating greater precision than for the easier target. Additionally, there was a reliable tendency for the hand reaching towards the more difficult target to lead. Importantly, it was the competing visuo-motor demands of individual movements rather than overall difficulty that resulted in greater between-limb asynchrony; accordingly, where both targets were small (i.e., the most difficult condition), asynchrony was significantly less pronounced than for incongruent bimanual conditions. The results show how the visuo-motor system balances its apparent drive for synchrony in coordinating bimanual movements with the competing demands that characterise the constituent unimanual movements.

Through the looking-glass: Mirror feedback modulates temporal and spatial aspects of bimanual coordination.

Mirror therapy has become an effective and recommended intervention for a range of conditions affecting the upper limb (e.g. hemiparesis following stroke). However, little is known about how mirror feedback affects the control of bimanual movements (as performed during mirror therapy). In this study, in preparation for future clinical investigations, we examined the kinematics of bimanual circle drawing in unimpaired participants both with (Experiment 1) and without (Experiment 2) a visual template to guide movement. In both experiments, 15 unimpaired right-handed participants performed self-paced continuous bimanual circle-drawing movements with a mirror/symmetrical coordination pattern. For the mirror condition, vision was directed towards the mirror in order to monitor the reflected limb. In the no mirror condition, the direction of vision was unchanged, but the mirror was replaced with an opaque screen. Movements of both hands were recorded using motion capture apparatus. In both experiments, the most striking feature of movements was that the hand behind the mirror drifted spatially during the course of individual trials. Participants appeared to be largely unaware of this marked positional change of their unseen hand, which was most pronounced when a template to guide movement was visible (Experiment 1). Temporal asynchrony between the limbs was also affected by mirror feedback in both experiments; in the mirror condition, illusory vision of the unseen hand led to a relative phase lead for that limb. Our data highlight the remarkable impact that the introduction of a simple mirror can have on bimanual coordination. Modulation of spatial and temporal features is consistent with the mirror inducing a rapid and powerful visual illusion, the latter appearing to override proprioceptive signals.

Hyperosmolarity-mediated mitochondrial dysfunction requires Transglutaminase-2 in human corneal epithelial cells.

Hyperosmolar-induced ocular surface cell death is a key mitochondria-mediated event in inflammatory eye diseases. Transglutaminase (TGM)-2, a cross-linking enzyme, is purported to mediate cell death, but its link to mitochondria is unclear. In the cornea, the integrity of the epithelial cells is important for maintaining transparency of the cornea and therefore functional vision. We evaluated the role of TGM-2 and its involvement in hyperosmolarity-stimulated mitochondrial cell death in human corneal epithelial (HCE-T) cells. HCE-T cell lines stably expressing either shRNA targeting TGM-2 (shTG) or scrambled shRNA (shRNA) were constructed. Hyperosmolar conditions reduced viability and increased mitochondrial depolarization in shRNA cells. However, hyperosmolarity failed to induce mitochondrial depolarization to the same extent in shTG cells. Transient overexpression of TGM-2 resulted in very high levels of TGM-2 expression in shTG and shRNA cells. In the case of shTG cells after overexpression of TGM-2, hyperosmolarity induced the same extent of mitochondrial depolarization as similarly treated shRNA cells. Overexpression of TGM-2 also elevated transamidase activity and reduced viability. It also induced mitochondrial depolarization, increased caspase-3/7 and -9 activity, and these increases were partially suppressed by pan-caspase inhibitor Z-VAD-FMK. Corneal epithelial apoptosis via mitochondrial dysfunction after hyperosmolar stimulation is partially dependent on TGM-2. This TGM-2-dependent mechanism occurs in part via caspase-3/7 and -9. Protection against mitochondrial stress in the ocular surface targeting TGM-2 may have important implications in the survival of cells in hyperosmolar stress.

Visit-to-visit changes in fasting blood sugar and the risk for cardiovascular disease and mortality in the Korean population: a nationwide population-based cohort study.

OBJECTIVE: The importance of continuous monitoring of fasting blood sugar (FBS) levels of diabetic patients has been established. MATERIALS AND METHODS: An observational prospective study was conducted. Our analysis included 1,700,796 individuals from the nationwide South Korean National Health Insurance System cohort. FBS variability was measured by standard deviation (SD). RESULTS: Kaplan-Meier curves demonstrated elevated disease probability in the higher FBS fluctuation group compared with the lower FBS fluctuation group. After adjusting for confounding variables, Cox proportional hazards analysis showed that the hazard ratios of 411 individuals in the highest quartile of SD variation of FBS were 1.77 (95% confidence interval 1.37-2.28, p<0.001) compared with the lowest quartile of SD variation of FBS. The impact of FBS fluctuation on the risk of cardiovascular diseases (CVDs), cerebrovascular diseases, CVD mortality and all-cause mortality in the highest quartiles of diabetic and non-diabetic individuals was statistically significant. CONCLUSIONS: Visit-to-visit FBS variability has prognostic value for predicting micro- and macrovascular disease, cardiovascular mortality, and all-cause mortality.

Bubble dynamics and cavitation intensity in milli-scale channels under an ultrasonic horn.

Under a vibrating ultrasonic horn device, intense cavitation occurs but is restricted to a small volume due to strong attenuation effects. In this study, milli-scale channels were introduced under the horn. The effect of this on the cavitation development and intensity within the channels were explored. High speed videography of up to 100,000 fps and acoustic signal acquisition through hydrophone were conducted. Cavitation intensity was observed to increase within the channels as compared to free field condition. Bubble density increased with a decrease in channel diameter and a rise in ultrasonic amplitude. Furthermore, an intriguing phenomenon of large bubble cluster formation near the channel exit (20 mm away from the horn surface) was detected. The oscillation behaviour of these clusters is dependent on both channel diameter and ultrasonic amplitude. At the maximum ultrasonic amplitude, the clusters reached maximum radiuses exceeding 3 mm and collapsed violently. Repetitive transient collapses near the exit region suggest that the introduction of milli-scale channels could extend the effective cavitation zone length and enhance the overall cavitation intensity under an ultrasonic horn.

Electromagnetic ray tracing model for line structures.

In this paper, a model for electromagnetic scattering of line structures is established based on high frequency approximation approach - ray tracing. This electromagnetic ray tracing (ERT) model gives the advantage of identifying each physical field that contributes to the total solution of the scattering phenomenon. Besides the geometrical optics field, different diffracted fields associated with the line structures are also discussed and formulated. A step by step addition of each electromagnetic field is given to elucidate the causes of a disturbance in the amplitude profile. The accuracy of the ERT model is also discussed by comparing with the reference finite difference time domain (FDTD) solution, which shows a promising result for a single polysilicon line structure with width of as narrow as 0.4 wavelength.

Kisspeptin neurones in the posterodorsal medial amygdala modulate sexual partner preference and anxiety in male mice.

The posterodorsal medial amygdala (MePD) is a neural site in the limbic brain involved in regulating emotional and sexual behaviours. There is, however, limited information available on the specific neuronal cell type in the MePD functionally mediating these behaviours in rodents. The recent discovery of a significant kisspeptin neurone population in the MePD has raised interest in the possible role of kisspeptin and its cognate receptor in sexual behaviour. The present study therefore tested the hypothesis that the MePD kisspeptin neurone population is involved in regulating attraction towards opposite sex conspecifics, sexual behaviour, social interaction and the anxiety response by selectively stimulating these neurones using the novel pharmacosynthetic DREADDs (designer receptors exclusively activated by designer drugs) technique. Adult male Kiss-Cre mice received bilateral stereotaxic injections of a stimulatory DREADD viral construct (AAV-hSyn-DIO-hM3 D(Gq)-mCherry) targeted to the MePD, with subsequent activation by i.p. injection of clozapine-N-oxide (CNO). Socio-sexual behaviours were assessed in a counter-balanced fashion after i.p. injection of either saline or CNO (5 mg kg-1 ). Selective activation of MePD kisspeptin neurones by CNO significantly increased the time spent by male mice in investigating an oestrous female, as well as the duration of social interaction. Additionally, after CNO injection, the mice appeared less anxious, as indicated by a longer exploratory time in the open arms of the elevated plus maze. However, levels of copulatory behaviour were comparable between CNO and saline-treated controls. These data indicate that DREADD-induced activation of MePD kisspeptin neurones enhances both sexual partner preference in males and social interaction and also decreases anxiety, suggesting a key role played by MePD kisspeptin in sexual motivation and social behaviour.

Visualisation of Kiss1 Neurone Distribution Using a Kiss1-CRE Transgenic Mouse.

Kisspeptin neuropeptides are encoded by the Kiss1 gene and play a critical role in the regulation of the mammalian reproductive axis. Kiss1 neurones are found in two locations in the rodent hypothalamus: one in the arcuate nucleus (ARC) and another in the RP3V region, which includes the anteroventral periventricular nucleus (AVPV). Detailed mapping of the fibre distribution of Kiss1 neurones will help with our understanding of the action of these neurones in other regions of the brain. We have generated a transgenic mouse in which the Kiss1 coding region is disrupted by a CRE-GFP transgene so that expression of the CRE recombinase protein is driven from the Kiss1 promoter. As expected, mutant mice of both sexes are sterile with hypogonadotrophic hypogonadism and do not show the normal rise in luteinising hormone after gonadectomy. Mutant female mice do not develop mature Graafian follicles or form corpora lutea consistent with ovulatory failure. Mutant male mice have low blood testosterone levels and impaired spermatogenesis beyond the meiosis stage. Breeding Kiss-CRE heterozygous mice with CRE-activated tdTomato reporter mice allows fluorescence visualisation of Kiss1 neurones in brain slices. Approximately 80-90% of tdTomato positive neurones in the ARC were co-labelled with kisspeptin and expression of tdTomato in the AVPV region was sexually dimorphic, with higher expression in females than males. A small number of tdTomato-labelled neurones was also found in other locations, including the lateral septum, the anterodorsal preoptic nucleus, the amygdala, the dorsomedial and ventromedial hypothalamic nuclei, the periaquaductal grey, and the mammillary nucleus. Three dimensional visualisation of Kiss1 neurones and fibres by CLARITY processing of whole brains showed an increase in ARC expression during puberty and higher numbers of Kiss1 neurones in the caudal region of the ARC compared to the rostral region. ARC Kiss1 neurones sent fibre projections to several hypothalamic regions, including rostrally to the periventricular and pre-optic areas and to the lateral hypothalamus.

Involvement of p27(kip1) in ceramide-mediated apoptosis in HL-60 cells.

Ceramide acts as a mediator of apoptosis in various cell lines, but little is known regarding the molecular mechanism linked to the cell cycle. In the present study, we examined the expression of p27(kip1) and its relationship to apoptosis induced by ceramide. We demonstrated that treatment of HL-60 cells with C6-ceramide resulted in G1 phase elevation followed by apoptotic cleavage associated with increase in the level of cdk inhibitor p27(kip1). Ceramide inhibited the kinase activities of cdk2 and cdk4 within 24 h of treatment. Ceramide-induced inhibition of cdk2 and cdk4 kinase activities was accompanied by increase of p27(kip1) in the cdks complexes. In addition, we have shown that both the cell death and expression of p27(kip1) protein induced by ceramide were significantly decreased in HL-60 cells overexpressing bcl-2. Furthermore, ceramide induced a significant increase in Bax protein expression coincided with increase in p27(kip1) protein level. These findings indicate that p27(kip1) may play important roles in mediating ceramide-induced apoptosis and its expression can be regulated by Bax and Bcl-2.

Norethisterone and levonorgestrel esters: a novel synthetic method.

Aliphatic, alicyclic and arylcarboxylic esters of norethisterone and levonorgestrel were prepared in a one-step synthesis and in near-quantitative yield using trifluoroacetic anhydride.

Placental chorioangioma: a case report and review.

Placental Chorioangioma occurs in 1% of pregnancies and are generally asymptomatic. However, they are known to cause a number of complications which are detrimental to the mother, fetus or the neonate. A typical case where acute polyhydramnios precipitated premature labour and delivery of the fetus as a result of a large placental chorioangioma is presented. A brief review of the other possible complications are also included.

Abdominal pregnancy: a case report and literature review.

We report a rare and unusual case of an Abdominal pregnancy that was delivered successfully at term. It is the first documented case in the local literature in almost 30 years. What makes it even more exceptional is that despite the high mortality associated with the condition, both mother and baby survived the ordeal. She subsequently delivered another child, 2 years later by an elective lower segment caesarean section and had a tubal ligation performed concomitantly. A review of the topic and its management is also presented.

Non-puerperal uterine inversion--a case report.

A rare case of non-puerperal uterine inversion caused by a large fundal leiomyoma in a 36-year-virgo intacta resulting in intractable haemorrhage was reported. After a myomectomy, attempts to reduce the inversion vaginally by transecting the anterior and posterior cervix was unsuccessful and a laparotomy was performed. The inversion was successfully corrected with return of normal function of the uterus.

Is postnatal oral glucose tolerance testing necessary in all women with gestational diabetes.

Currently, women with gestational diabetes mellitus have a repeat oral glucose tolerance test 6 weeks after delivery to identify those with persistent glucose intolerance. In this study, 298 women with gestational diabetes had a postnatal oral glucose tolerance test and of these, 23.2% had persistent glucose intolerance after delivery. The aim of this study was to determine if the antenatal oral glucose tolerance test results could be used to predict which patients would have persistent glucose intolerance after delivery. If only those with severely abnormal antenatal results had persistent disease, then those with only mildly abnormal antenatal results could be spared the postnatal oral glucose tolerance test. Using receiver operator characteristic curves, this study showed that the antenatal oral glucose tolerance test results could not be used to predict reliably which patients would continue to have abnormal glucose tolerance postnatally. Hence, postnatal oral glucose tolerance testing of all patients with gestational diabetes is still necessary as the detection of persistent glucose intolerance is important for the control of the diabetic condition so as to minimise long-term complications.

Local norms of maternal serum alpha-fetoprotein values in early second trimester: a prelude to a Down's syndrome screening programme incorporating maternal serum alpha-fetoprotein values.

Maternal alpha-fetoprotein in (MSAFP) has recently been proposed for screening of Down's syndrome. This is based on the association of a lowered MSAFP level at a given gestational age in Down's syndrome (DS) pregnancies. Most conventional 'screening' programmes in DS are based on the maternal age alone, selecting older mothers, who are at greater risk of having a DS infant born, for antenatal karyotyping. However, as 75% of DS infants are born to mothers less than 35 years old, a combination of blood tests including MSAFP and maternal age as independent risk factors would screen the younger mothers as a good cost-benefit ratio in selecting the 'at-risk' mothers for karyotyping. In this study, the gestational age was calculated from the first day of the last menstrual period (LMP) as well as from ultrasound cephalometry. The local MSAFP levels follow the same trend at a slightly higher level as those based on clinical evaluation of the Abbot AFP-EIA Monoclonal kits.

Pericentric inversion 9--incidence and clinical significance.

Pericentric inversion of the chromosome 9, inv(9)(p11q13), is such a common occurrence that some cytogeneticists would consider them as normal variants. The incidence is said to be about 1% to 1.65% in the general population. Despite being categorised as a minor chromosomal rearrangement which does not correlate with abnormal phenotypes, many reports in the literature raised conflicting views regarding the association with subfertility and recurrent abortions, abnormal clinical conditions, as well as chromosomal abnormalities arising as a result of having this inversion. We studied the incidence and clinical significance of inv(9)(p11q13) patients retrospectively from 2448 antenatal cytogenetic analysis and 1058 peripheral blood karyotype collected over a 3-year period. Thirty cases of inv(9)(p11q13) from 29 families were found from the antenatal group, which gave an incidence of 1.2% and 6 cases from the peripheral blood karyotype analysis (incidence of 0.6%). The parental origin of the inv(9)(p11q13) in the antenatal group was of equal proportion and there was also no sex predilection for the fetuses carrying the inversion. The babies with the inversion were born with no phenotypic abnormalities. The 6 cases picked up from the peripheral blood karyotype analysis were 2 cases of paediatric patients with associated chromosomal abnormalities (one Trisomy 21 and the other del 13(q22q32)) and 4 adult patients with obstetric and fertility problems. The incidence of subfertility (36%) appeared to be high amongst the adult patients with inv(9)(p11q13). This may represent a true reflection of subfertility in inv(9)(p11q13) patients or a selective bias towards the older subfertile women who conceive at a later age and thus utilising the antenatal diagnostic setup.

Inertia sensor-based guidance system for upperlimb posture correction.

Stroke rehabilitation is labor-intensive and time-consuming. To assist patients and therapists alike, we propose a wearable system that measures orientation and corrects arm posture using vibrotactile actuators. The system evaluates user posture with respect to a reference and gives feedback in the form of vibration patterns. Users correct their arm posture, one DOF at a time, by following a protocol starting from the shoulder up to the forearm. Five users evaluated the proposed system by replicating ten different postures. Experimental results demonstrated system robustness and showed that some postures were easier to mimic depending on their naturalness.

Immunohistochemical evidence for the presence of various kisspeptin isoforms in the mammalian brain.

Kisspeptins are small peptides encoded by the Kiss1 gene that have been the focus of intense neuroendocrine research during the last decade. Kisspeptin is now considered to have important roles in the regulation of puberty onset and adult oestrogen-dependent feedback mechanisms on gonadotrophin-releasing hormone secretion. Several kisspeptin antibodies have been generated that have enabled an overall view of kisspeptin peptide distribution in the brain of many mammalian species. However, it remains that the distribution of the different kisspeptin isoforms is unclear in the mammalian brain. In the present study, we report on two new N-terminal-directed kisspeptin antibodies, one against the mouse kisspeptin-52 sequence (AC053) and one against the rat kisspeptin-52 sequence (AC067), and use them to specifically map these long isoforms in the brains of mouse and rat, respectively. Kisspeptin-52 immunoreactivity was detected in the two main kisspeptin neuronal populations of the rostral periventricular area and arcuate nucleus but not in the dorsomedial hypothahamus. A large number of fibres throughout the ventral forebrain were also labelled with these two antibodies. Finally, a comparison with the most commonly used C-terminal-directed kisspeptin antibodies further suggests the presence of shorter kisspeptin fragments in the brain with specific inter- and intracellular expression patterns.

Subacute thyroiditis presenting as a focal lesion on [18F] fluorodeoxyglucose whole-body positron-emission tomography/CT.

A 52-year-old man presented with subacute thyroiditis and showed an intensely hypermetabolic thyroid lesion on (18)F-FDG PET/CT. The patient also had coexisting chronic lymphocytic thyroiditis. The lesion of subacute thyroiditis revealed an SUV(max) of 9.1 g/mL and was ill-defined, heterogeneous, markedly hypoechoic, and hypovascular on US. Biopsy demonstrated histologic findings of subacute thyroiditis, which should be included in the differential diagnosis of an intensely hypermetabolic thyroid lesion on (18)F-FDG PET/CT.