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Effective learning in old age, particularly in those at risk for dementia, is essential for prolonging independent living. Individual variability in learning, however, is remarkable; that is, months of cognitive training to improve learning may be beneficial for some individuals but not others. So far, little is known about which neurophysiological mechanisms account for the observed variability in learning induced by cognitive training in older adults. By combining Lövdén et al.'s (2010, A theoretical framework for the study of adult cognitive plasticity. Psychological Bulletin, 136, 659–676) framework proposing the role of adaptation capacity in neuroplasticity and a neurovisceral integration model of the relationship between autonomic nervous system (ANS) and brain with a novel shapelet analytical approach that allows for accurate and interpretable analysis of time series data, we discovered an acute, ECG‐derived ANS segment in response to cognitive training tasks at baseline that predicted learning outcomes from a 6‐week cognitive training intervention. The relationship between the ANS segment and learning was robust in both cross‐participant and cross‐task analyses among a group of older adults with amnestic mild cognitive impairment. Furthermore, the revealed ANS shapelet significantly predicted training‐induced neuroplasticity in the dorsal anterior cingulate cortex and select frontal regions during task fMRI. Across outcome measures, individuals were less likely to prospectively benefit from the cognitive training if their ECG data were more similar to this particular ANS segment at baseline. Our findings are among the first empirical evidence to confirm that adaptation capacity, indexed by ANS flexibility, predicts individual differences in learning and associated neuroplasticity beyond individual characteristics (e.g., age, education, neurodegeneration, total training)., We provide first line of empirical evidence confirming the theoretical relationship between adaptation capacity, ANS flexibility is a main indictor of which, and neuroplasticity. The identified ANS segment can help determine which individuals may be more responsive to a particular cognitive training.

Stroke damage to the primary visual cortex (V1) causes a loss of vision known as hemianopia or cortically-induced blindness. While perimetric visual field improvements can occur spontaneously in the first few months post-stroke, by 6 months post-stroke, the deficit is considered chronic and permanent. Despite evidence from sensorimotor stroke showing that early injury responses heighten neuroplastic potential, to date, visual rehabilitation research has focused on patients with chronic cortically-induced blindness. Consequently, little is known about the functional properties of the post-stroke visual system in the subacute period, nor do we know if these properties can be harnessed to enhance visual recovery. Here, for the first time, we show that ‘conscious’ visual discrimination abilities are often preserved inside subacute, perimetrically-defined blind fields, but they disappear by ∼6 months post-stroke. Complementing this discovery, we now show that training initiated subacutely can recover global motion discrimination and integration, as well as luminance detection perimetry, just as it does in chronic cortically-induced blindness. However, subacute recovery was attained six times faster; it also generalized to deeper, untrained regions of the blind field, and to other (untrained) aspects of motion perception, preventing their degradation upon reaching the chronic period. In contrast, untrained subacutes exhibited spontaneous improvements in luminance detection perimetry, but spontaneous recovery of motion discriminations was never observed. Thus, in cortically-induced blindness, the early post-stroke period appears characterized by gradual—rather than sudden—loss of visual processing. Subacute training stops this degradation, and is far more efficient at eliciting recovery than identical training in the chronic period. Finally, spontaneous visual improvements in subacutes were restricted to luminance detection; discrimination abilities only recovered following deliberate training. Our findings suggest that after V1 damage, rather than waiting for vision to stabilize, early training interventions may be key to maximize the system’s potential for recovery.

Despite high prevalence of patients with gastric disease in systemic sclerosis (SSc), its pathogenesis is still poorly understood. We immunohistochemically analysed biopsies of gastric mucosa (GM) in 5 controls and 15 patients with different forms of SSc: limited cutaneous (lc), diffuse cutaneous moderate (sys1) and severe (sys2). The number of positive cells was analysed by a Kruskall-Wallis test, P

Numerous behavioral studies have shown that visual function can improve with training, although perceptual refinements generally require weeks to months of training to attain. This, along with questions about long-term retention of learning, limits practical and clinical applications of many such paradigms. Here, we show for the first time in female and male human participants that just 10 d of visual training coupled with transcranial random noise stimulation (tRNS) over visual areas causes dramatic improvements in visual motion perception. Relative to control conditions and anodal stimulation, tRNS-enhanced learning was at least twice as fast, and, crucially, it persisted for 6 months after the end of training and stimulation. Notably, tRNS also boosted learning in patients with chronic cortical blindness, leading to recovery of motion processing in the blind field after just 10 d of training, a period too short to elicit enhancements with training alone. In sum, our results reveal a remarkable enhancement of the capacity for long-lasting plastic and restorative changes when a neuromodulatory intervention is coupled with visual training. SIGNIFICANCE STATEMENT Our work demonstrates that visual training coupled with brain stimulation can dramatically reduce the training period from months to weeks, and lead to fast improvement in neurotypical subjects and chronic cortically blind patients, indicating the potential of our procedure to help restore damaged visual abilities for currently untreatable visual dysfunctions. Together, these results indicate the critical role of early visual areas in perceptual learning and reveal its capacity for long-lasting plastic changes promoted by neuromodulatory intervention.

Background: Coronary artery bypass grafting (CABG) surgery continues to be the gold standard for treating the patients with coronary artery disease. CABG surgery can be performed on or off cardiopulmonary bypass, termed as on-pump or off-pump CABG, respectively. It has been shown that CABG surgery, preferably on-pump CABG surgery, leads to the changes of cell immunity during perioperative and early postoperative period. The mechanisms of regulation of the immune response in patients during and early after surgical revascularization are not fully understood. The aim of this study was to investigate the influence of carbohydrate preoperative oral feeding on frequency and perforin expression in peripheral blood lymphocytes in patients after on- or off-pump CABG surgery in early postoperative period. Patients and methods: In this prospective clinical study, 80 patients scheduled for CABG surgery were included in the study. The patients were randomly allocated into four groups (20 in each group): patients in Group 1 underwent on-pump CABG and did not receive carbohydrate preoperative oral feeding; patients in Group 2 underwent on-pump CABG and were preoperatively fed; patients in Group 3 underwent off-pump CABG and did not receive carbohydrate preoperative oral feeding; while patients in Group 4 underwent off-pump CABG and received carbohydrate preoperative oral feeding. Blood samples were collected immediately before (T1), 24 (T2) and 72 (T3) hours after the surgery. Peripheral blood mononuclear cells were isolated by gradient centrifugation and simultaneously labelled by antigens using fluorochrome-conjugated monoclonal antibodies. Frequency of T lymphocytes, NK and NKT cells, their subsets as well as their perforin expression were detected, and analyzed by flow cytometry. Results: There was significant decrease in frequency of CD3+ and CD3+CD4+ cells, as well as perforin expressing CD3+CD8+ cells in patients who underwent on-pump CABG in comparison to patients who underwent off-pump CABG 24 hours after the surgery. Carbohydrate preoperative oral feeding did not effect changes in lymphocytes subpopulations and perforin expression at any time point. Conclusion: Decreases of CD3+ cells on account of CD3+CD4+ subsets, and perforin expressing cells on account of CD3+CD8+ perforin+ cells were found in patients who had undergone on-pump CABG, but not in patients who had undergone off-pump CABG surgery, irrespectively of carbohydrate preoperative oral feeding.

Visual perceptual learning (VPL) can lead to long-lasting perceptual improvements. While the efficacy of VPL is well established, there is still a considerable debate about what mechanisms underlie the effects of VPL. Much of this debate concentrates on where along the visual processing hierarchy behaviorally relevant plasticity takes place. Here, we aimed to tackle this question in context of motion processing, a domain where links between behavior and processing hierarchy are well established. Specifically, we took advantage of an established transition from component-dependent representations at the earliest level to pattern-dependent representations at the middle-level of cortical motion processing. We trained two groups of participants on the same motion direction identification task using either grating or plaid stimuli. A set of pre- and post-training tests was used to determine the degree of learning specificity and generalizability. This approach allowed us to disentangle contributions from both low- and mid-level motion processing, as well as high-level cognitive changes. We observed a complete bi-directional transfer of learning between component and pattern stimuli as long as they shared the same apparent motion direction. This result indicates learning-induced plasticity at intermediate levels of motion processing. Moreover, we found that motion VPL is specific to the trained stimulus direction, speed, size, and contrast, highlighting the pivotal role of basic visual features in VPL, and diminishing the possibility of non-sensory decision-level enhancements. Taken together, our study psychophysically examined a variety of factors mediating motion VPL, and demonstrated that motion VPL most likely alters visual computation in the middle stage of motion processing.

Objectives: This study assessed the frequency of nuclear morphological changes in gingival epithelial cells, as a biomarker for DNA damage, in individuals with periodontitis, before and after implementation of periodontal therapy, and compared the morphology to those with healthy periodontal tissues. Materials and methods: Exfoliated gingival cells were taken from 30 participants without periodontal destruction in any teeth and 30 participants with periodontitis before and after 45 and 90 days following treatment. Nuclear morphological changes were analyzed using the micronucleus test. Results: Compared with the healthy volunteers, those with periodontitis had a significant increase in the number of cells with nuclear broken eggs (P = 0.048), condensed chromatin (P = 0.015), karyolysis (P < 0.001), or binuclei (P < 0.001). In the periodontitis group, the pretreatment frequencies of cells with micronuclei (P = 0.008), binuclei (P < 0.001), karyolysis (P = 0.038), nuclear buds (P = 0.005), and condensed chromatin (P = 0.015) were significantly higher than 90 days after treatment. Conclusion: Our observations suggest that periodontal disease increases the frequency of nuclear morphological changes in gingival epithelial cells and that the implementation of periodontal therapy was associated with a reduction of that number. Clinical relevance: The micronucleus test could serve as a tool for estimating genotoxic damage in assessing the success of periodontal therapy

Perceptual anomalies in individuals with autism spectrum disorder (ASD) have been attributed to an imbalance in weighting incoming sensory evidence with prior knowledge when interpreting sensory information. Here, we show that sensory encoding and how it adapts to changing stimulus statistics during feedback also characteristically differs between neurotypical and ASD groups. In a visual orientation estimation task, we extracted the accuracy of sensory encoding from psychophysical data by using an information theoretic measure. Initially, sensory representations in both groups reflected the statistics of visual orientations in natural scenes, but encoding capacity was overall lower in the ASD group. Exposure to an artificial (i.e., uniform) distribution of visual orientations coupled with performance feedback altered the sensory representations of the neurotypical group toward the novel experimental statistics, while also increasing their total encoding capacity. In contrast, neither total encoding capacity nor its allocation significantly changed in the ASD group. Across both groups, the degree of adaptation was correlated with participants’ initial encoding capacity. These findings highlight substantial deficits in sensory encoding—independent from and potentially in addition to deficits in decoding—in individuals with ASD., It is increasingly recognized that individuals with Autism Spectrum Disorder (ASD) show anomalies in perception, and these have been recently attributed to altered decoding (i.e. interpretation of sensory signals). This study reveals that independent of these changes, individuals with ASD show upstream deficits in sensory encoding (i.e., how samples are drawn from the environment).

Stereovision is the ability to perceive fine depth variations from small differences in the two eyes' images. Using adaptive optics, we show that even minute optical aberrations that are not clinically correctable, and go unnoticed in everyday vision, can affect stereo acuity. Hence, the human binocular system is capable of using fine details that are not experienced in everyday vision. Interestingly, stereo acuity varied considerably across individuals even when they were provided identical perfect optics. We also found that individuals' stereo acuity is better when viewing with their habitual optics rather than someone else's (better) optics. Together, these findings suggest that the visual system compensates for habitual optical aberrations through neural adaptation and thereby optimizes stereovision uniquely for each individual. Thus, stereovision is limited by small optical aberrations and by neural adaptation to one's own optics.

The eye’s optics are a major determinant of visual perception. Elucidating how long-term exposure to optical defects affects visual processing is key to understanding the capacity for, and limits of, sensory plasticity. Here, we show evidence of functional reallocation of sensory processing resources following long-term exposure to poor optical quality. Using adaptive optics to bypass all optical defects, we assessed visual processing in neurotypically-developed adults with healthy eyes and with keratoconus – a corneal disease causing severe optical aberrations. Under fully-corrected optical conditions, keratoconus patients showed altered contrast sensitivity, with impaired sensitivity for fine spatial details and better-than-typical sensitivity for coarse spatial details. Both gains and losses in sensitivity were more pronounced in patients experiencing poorer optical quality in their daily life and mediated by changes in signal enhancement mechanisms. These findings show that adult neural processing adapts to better match the changes in sensory inputs caused by long-term exposure to altered optics.

Aim To investigate the demographic characteristics, endoscopic and laboratory findings, comorbidities and mortality rate of patients with gastrointestinal bleeding related to anticoagulant or antiplatelet therapy. Methods We reviewed the records of patients admitted for gastrointestinal bleeding to the Intensive Care Unit of the Department of Gastroenterology, University Hospital Split, between 2015 and 2019. The characteristics and clinical outcomes of patients taking anticoagulant/antiplatelet therapy were analyzed. Results The study enrolled 1367 patients, 434 (31.7%) of whom received anticoagulant/antiplatelet therapy (mean age 74.9±10.7 years; 64.3% men). The most frequently prescribed drug was acetylsalicylic acid (56.7%), the most common bleeding site was the stomach (41.3%), and the most prevalent cause of bleeding was ulcer (61.6%). Patients taking anticoagulant/antiplatelet therapy who died had significantly higher creatinine (P=0.011) and lower albumin (P=0.015). In the multivariate analysis, the factors that negatively affected survival were older age, higher creatinine, and lower albumin. Patients taking anticoagulant/antiplatelet therapy had slightly lower in-hospital mortality (8.3%) compared with other patients (10.3%). Conclusion Although anticoagulant/antiplatelet therapy increases the risk of gastrointestinal bleeding, it does not directly affect the outcome, which is mainly determined by age and comorbidities.

A specific diet regimen is a promising way of managing inflammatory bowel disease (IBD), with the Mediterranean diet (MD) being a likely candidate due to its potential to modulate gut inflammation. Therefore, the aim of this study was to investigate nutritional habits and dietary attitudes of IBD patients, and to assess their adherence to the Mediterranean diet. The study enrolled 50 Crohn&rsquo, s disease and 44 ulcerative colitis patients, with clinical and laboratory parameters taken. Dietary attitudes were examined, and adherence to MD was assessed using the Mediterranean Diet Service Score (MDSS). Average MDSS score was 6.0 (5.0&ndash, 7.0), while only nine participants fulfilled criteria for Mediterranean diet adherence. Moreover, all of them were men (p = 0.021). Low percentage of adherence to recommended guidelines was observed for eating olive oil (25.5%), fresh fruit (14.9%), and vegetables (10.6%). Significant positive correlation was observed between total MDSS points and high-density lipoprotein (HDL) cholesterol levels (p = 0.002). The majority of the patients (86.2%) considered that a more controlled diet could reduce their IBD symptoms, while 17% visited a nutritionist for diet advice. The majority of patients (84%) would visit educational programs regarding nutrition. In conclusion, adherence to MD was very low, while IBD patients were willing to extend their nutritional knowledge if proper educational programs were organized.

Adropin is a novel peptide mostly associated with energy homeostasis and vascular protection. To our knowledge, there are no studies that investigated its relationship with inflammatory bowel diseases (IBD). The aim of this study was to compare serum adropin levels between 55 patients with IBD (30 Ulcerative colitis (UC) patients, 25 Crohn’s disease (CD) patients) and 50 age/gender matched controls. Furthermore, we explored adropin correlations with IBD severity scores, hsCRP, fecal calprotectin, fasting glucose and insulin levels. Serum adropin levels were significantly lower in patients with IBD in comparison with the control group (2.89 ± 0.94 vs 3.37 ± 0.60 ng/mL, P = 0.002), while there was no significant difference in comparison of UC patients with CD patients (P = 0.585). Furthermore, there was a negative correlation between adropin and fecal calprotectin (r = −0.303, P = 0.025), whereas in the total study population, we found a significant negative correlation with fasting glucose levels (r = −0.222, P = 0.023). A multivariable logistic regression showed that serum adropin was a significant predictor of positive IBD status when enumerated along with baseline characteristics (OR 0.455, 95% CI 0.251–0.823, P = 0.009). Our findings imply that adropin could be involved in complex pathophysiology of IBD, but further larger scale studies are needed to address these findings.

A 27-year-old man presents with successfully resuscitated ventricular fibrillation. Structural and electrical causes of ventricular fibrillation in the young are presented along with a diagnostic strategy. Electrocardiographic features of malignant early repolarization are discussed.

Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined and diagnosed by core deficits in social communication and the presence of restricted and repetitive behaviors. Research on face processing suggests deficits in this domain in ASD but includes many mixed findings regarding the nature and extent of these differences. The first eye movement to a face has been shown to be highly informative and sufficient to achieve high performance in face identification in neurotypical adults. The current study focused on this critical moment shown to be essential in the process of face identification. Methods We applied an established eye-tracking and face identification paradigm to comprehensively characterize the initial eye movement to a face and test its functional consequence on face identification performance in adolescents with and without ASD (n = 21 per group), and in neurotypical adults. Specifically, we presented a series of faces and measured the landing location of the first saccade to each face, while simultaneously measuring their face identification abilities. Then, individuals were guided to look at specific locations on the face, and we measured how face identification performance varied as a function of that location. Adolescent participants also completed a more traditional measure of face identification which allowed us to more fully characterize face identification abilities in ASD. Results Our results indicate that the location of the initial look to faces and face identification performance for briefly presented faces are intact in ASD, ruling out the possibility that deficits in face perception, at least in adolescents with ASD, begin with the initial eye movement to the face. However, individuals with ASD showed impairments on the more traditional measure of face identification. Conclusion Together, the observed dissociation between initial, rapid face perception processes, and other measures of face perception offers new insights and hypotheses related to the timing and perceptual complexity of face processing and how these specific aspects of face identification may be disrupted in ASD.

Segregation of objects from their backgrounds is a fundamental visual function and one that is particularly effective when objects are in motion. Theoretically, suppressive center-surround mechanisms are well suited for accomplishing motion segregation. This longstanding hypothesis, however, has received limited empirical support. We report converging correlational and causal evidence that spatial suppression of background motion signals is critical for rapid segmentation of moving objects. Motion segregation ability is strongly predicted by both individual and stimulus-driven variations in spatial suppression strength. Moreover, aging-related superiority in perceiving background motion is associated with profound impairments in motion segregation. This segregation deficit is alleviated via perceptual learning, but only when motion segregation training also causes decreased sensitivity to background motion. We argue that perceptual insensitivity to large moving stimuli effectively implements background subtraction, which, in turn, enhances the visibility of moving objects and accounts for the observed link between spatial suppression and motion segregation., The visual system excels at segregating moving objects from their backgrounds, a key visual function hypothesized to be driven by suppressive centre-surround mechanisms. Here, the authors show that spatial suppression of background motion signals is critical for rapid segmentation of moving objects.

Objectives: The present study addresses the effect of fluoride and sodium lauryl sulfate content of toothpaste on oral epithelial cells in vivo conditions. Subjects and method: Forty volunteers were assigned into two experimental groups, each of them applying the different brand of toothpaste. Every group has been using three different types of toothpaste (non- fluoride and non-SLS, fluoride and non-SLS, and the fluoride and SLS) of the same brand for six months, each for two months. The buccal epithelial cells were sampled at baseline and 30, 60, 90, 120, 150 and 180 days after the beginning of the research. Effect on DNA damage was analyzed by micronucleus assay Results: After 60 days of use, for both tested kinds of toothpaste with fluoride and without SLS, all studied parameters were not significantly different from the results obtained at the time when the participants used a non-fluoride toothpaste. While, after 60 days of use, for one kind of toothpaste with SLS and fluoride, was observed significantly higher incidence of pyknotic cells (2.20±0.95, 0.00±0.00 vs 0.05±0.22, respectively ; p=.001), cells with karyorrhexis (2.35±1.14, 0.85±0.93 vs 0.40±0.68, respectively ; p=.001), and nuclear buds (1.35±0.68, 0.45±0.51 vs 0.45±0.60, respectively ; p=.001), compared to toothpastes of the same brand with fluoride and without SLS, and without fluoride and without SLS, for the same period. Conclusion: Based on the results, can be concluded that there is no fluorine- dependent cytotoxic or genotoxic effect, while SLS dentifrice increases the number of nuclear morphological changes in buccal epithelial cells.

SREBP cleavage-activating protein (SCAP) is a key protein in the regulation of lipid metabolism and a potential target for treatment of dyslipidemia. SCAP is required for activation of the transcription factors SREBP-1 and -2. SREBPs regulate the expression of genes involved in fatty acid and cholesterol biosynthesis, and LDL-C clearance through the regulation of LDL receptor (LDLR) and PCSK9 expression. To further test the potential of SCAP as a novel target for treatment of dyslipidemia, we used siRNAs to inhibit hepatic SCAP expression and assess the effect on PCSK9, LDLR, and lipids in mice and rhesus monkeys. In mice, robust liver Scap mRNA knockdown (KD) was achieved, accompanied by dose-dependent reduction in SREBP-regulated gene expression, de novo lipogenesis, and plasma PCSK9 and lipids. In rhesus monkeys, over 90% SCAP mRNA KD was achieved resulting in approximately 75, 50, and 50% reduction of plasma PCSK9, TG, and LDL-C, respectively. Inhibition of SCAP function was demonstrated by reduced expression of SREBP-regulated genes and de novo lipogenesis. In conclusion, siRNA-mediated inhibition of SCAP resulted in a significant reduction in circulating PCSK9 and LDL-C in rodent and primate models supporting SCAP as a novel target for the treatment of dyslipidemia.

Adaptation capacity is critical for maintaining cognition, yet it is understudied in groups at risk for dementia. Autonomic nervous system (ANS) is critical for neurovisceral integration and is a key contributor to adaptation capacity. To determine the central nervous system’s top-down regulation on ANS, we conducted a mechanistic randomized controlled trial study, using a 6-week processing speed and attention (PS/A) targeted intervention. Eighty-four older adults with amnestic mild cognitive impairment (aMCI) were randomized to a 6-week PS/A-targeted intervention or an active control without PS/A. Utilizing repeated measures (i.e., PS/A test different from the intervention, resting and cognitive task-based ECG, and resting fMRI) at baseline, immediately post-intervention (post-test), and 6-month follow-up, we aimed to test whether there is a causal influence of PS/A on vagal control of ANS via their shared central neural pathways in aMCI. We indexed vagal control of ANS using high-frequency heart rate variability (HF-HRV) extracted from ECG data. Functional brain connectivity patterns were extracted from fMRI using advanced statistical tools. Compared to the control group, the intervention group showed significant improvement in PS/A, HF-HRV, salience network (SN), central executive network (CEN), and frontal parietal network (FPN) connectivity at post-test; the effect on SN, CEN, and FPN remained at 6-month follow-up. Changes in PS/A and SN connectivity significantly predicted change in HF-HRV from baseline to post-test and/or 6-month-follow-up. Age, neurodegeneration, nor sex did not affect these relationships. This work provides novel support for top-down regulation of PS/A and associated SN on vagal control of ANS. Intervening PS/A may be a viable approach for promoting adaptation capacity in groups at risk for dementia.

Purpose: This is a cross-sectional study to assess the incidence of micronuclei and other nuclear morphological changes in buccal epithelial cells of dental technicians. Materials and Methods: The study was conducted on 45 dental technicians vs. 2 control groups: 50 dentists and 50 dental assistants. DNA damage was analyzed in exfoliated buccal mucosa cells by micronucleus assay. The differences in the frequency of detected types of cytogenetic damage between experimental groups were analyzed by applying 2-way ANOVA with Tukey's HSD post- hoc test. Results: Dentists and dental assistants have significantly lower incidence of micronucleated cells than technicians (mean ± SD: 0.68 ± 0.74, 0.58 ± 0.81, and 1.58 ± 2.07 ; p = 0.031 and p = 0.015, respectively), and this trend also holds for karyolitic cells (0.10 ± 0.30, 0.20 ± 0.49, and 1.42 ± 1.25 ; p < 0.001 and p < 0.001, respectively), condensed chromatin (0.16 ± 0.37, 0.14 ± 0.35, and 0.76 ± 0.98 ; p < 0.001 and p < 0.001, respectively), and pyknotic cells (0.04 ± 0.20, 0.08 ± 0.27, and 0.96 ± 1.24 ; p < 0.001 and p < 0.001, respectively). Conclusion: Cytogenetic biomarkers in dental technician buccal mucosa are increased compared with control groups. This increase may be associated with more extensive exposure to potentially harmful components of the materials used in everyday dental practice.

BACKGROUND: It is important to understand how the psychological status of parents affects oral health in children. AIM: This study aimed to assess the level of depression, anxiety, and stress of parents whose children have early- childhood caries. DESIGN: The study included 235 children and their parents who visited the Dental clinic at the School of Medicine of the University of Split between October 2016 and July 2017. The dental status of each child was recorded, while parents filled out the Depression Anxiety Stress Scale questionnaire and the questionnaire related to the demographic characteristics, questions related to child's habits of the tooth brushing, eating sweets. RESULTS: Multiple regression analysis showed that the incidence of active caries in the children was statistically significantly related not only to the level of parent depression (β = -0.289 ; P = 0.040) but also the level of anxiety (β = 0.186 ; P = 0.038) and stress (β = -0.120 ; P = 0.036). The dmft index in the examined children was negatively significant associated with the parental level of depression (β = -0.305 ; P = 0.032). CONCLUSION: Considering the results of our research it is essential to emphasize the need for better health education of parents.

Summary The importance of sex as a biological variable has recently been emphasized by major funding organizations [ 1 ] and within the neuroscience community [ 2 ]. Critical sex-based neural differences are indicated by, for example, conditions such as autism spectrum disorder (ASD) that have a strong sex bias with a higher prevalence among males [ 51 , 3 ]. Motivated by this broader context, we report a marked sex difference in a visual motion perception task among neurotypical adults. Motion duration thresholds [ 4 , 5 ]—the minimum duration needed to accurately perceive motion direction—were considerably shorter for males than females. We replicated this result across three laboratories and 263 total participants. This type of enhanced performance has previously been observed only in special populations including ASD, depression, and senescence [ 6 , 7 , 8 ]. The observed sex difference cannot be explained by general differences in speed of visual processing, overall visual discrimination abilities, or potential motor-related differences. We also show that while individual differences in motion duration thresholds are associated with differences in fMRI responsiveness of human MT+, surprisingly, MT+ response magnitudes did not differ between males and females. Thus, we reason that sex differences in motion perception are not captured by an MT+ fMRI measure that predicts within-sex individual differences in perception. Overall, these results show how sex differences can manifest unexpectedly, highlighting the importance of sex as a factor in the design and analysis of perceptual and cognitive studies.

An emerging hypothesis postulates that internal noise is a key factor influencing perceptual abilities in autism spectrum disorder (ASD). Given fundamental and inescapable effects of noise on nearly all aspects of neural processing, this could be a critical abnormality with broad implications for perception, behavior, and cognition. However, this proposal has been challenged by both theoretical and empirical studies. A crucial question is whether and how internal noise limits perception in ASD, independently from other sources of perceptual inefficiency, such as the ability to filter out external noise. Here, we separately estimated internal noise and external noise filtering in ASD. In children and adolescents with and without ASD, we computationally modeled individuals’ visual orientation discrimination in the presence of varying levels of external noise. The results revealed increased internal noise and worse external noise filtering in individuals with ASD. For both factors, we also observed high inter-individual variability in ASD, with only the internal noise estimates significantly correlating with severity of ASD symptoms. We provide evidence for reduced perceptual efficiency in ASD that is due to both increased internal noise and worse external noise filtering, while highlighting internal noise as a possible contributing factor to variability in ASD symptoms.

This study aimed to evaluate possible DNA damages to oral epithelial cells exposed to whitening kinds of toothpaste considering the effect of conventional non-whitening toothpaste. Sixty volunteers were assigned into three experimental groups, each of them using a different regular toothpaste for the initial 2 months, followed by the use of whitening kind of toothpaste of the same brand for next 2 months. The oral epithelial cells were sampled prior and 30, 60, 90 and 120 days after the beginning of the use of tested kinds of toothpaste. Chromosomal damages were analyzed by micronucleus assay. For just one kind of tested whitening toothpaste was observed the significant increase in the number of micronucleated cells after 60 days of use compared values obtained 60 days of usage of conventional non-whitening toothpaste (6.35 ± 3.67 and 2.8± 1.91 ; p

Background: Vision-based speed of processing (VSOP) training can result in broad cognitive improvements in older adults with amnestic mild cognitive impairment (aMCI). What remains unknown, however, is what neurophysiological mechanisms account for the observed training effect. Much of the work in this area has focused on the central nervous system, neglecting the fact that the peripheral system can contributes to changes of the central nervous system and vice versa. Objective: We examined the prospective relationship between an adaptive parasympathetic nervous system response to cognitive stimuli and VSOP training-induced plasticity. Method: Twenty-one participants with aMCI (10 for VSOP training, and 11 for mental leisure activities (MLA) control) were enrolled. We assessed high-frequency heart rate variability (HF-HRV) during training sessions, and striatum-related neural networks and cognition at baseline and post-training. Results: Compared to MLA, the VSOP group showed a significant U-shaped pattern of HF-HRV response during training, as well as decreases in connectivity strength between bilateral striatal and prefrontal regions. These two effects were associated with training-induced improvements in both the trained (attention and processing speed) and transferred (working memory) cognitive domains. Conclusion: This work provides novel support for interactions between the central and the peripheral nervous systems in relation to cognitive training, and motivates further studies to elucidate the causality of the observed link.

Damage to the primary visual cortex (V1) or its immediate afferents results in a dense scotoma, termed cortical blindness (CB). CB subjects have residual visual abilities, or blindsight, which allow them to detect and sometimes discriminate stimuli with high temporal and low spatial frequency content. Recent work showed that with training, discriminations in the blind field can become more reliable, and even reach consciousness. However, the narrow spatiotemporal bandwidth of blindsight limits its functional usefulness in everyday vision. Here, we asked whether visual training can induce recovery outside the spatiotemporal bandwidth of blindsight. Specifically, could human CB subjects learn to discriminate static, nonflickering stimuli? Can such learning transfer to untrained stimuli and tasks, and does double training with moving and static stimuli provide additional advantages relative to static training alone? We found CB subjects capable of relearning static orientation discriminations following single as well as double training. However, double training with complex, moving stimuli in a separate location was necessary to recover complex motion thresholds at locations trained with static stimuli. Subjects trained on static stimuli alone could only discriminate simple motion. Finally, both groups had approximately equivalent, incomplete recovery of fine orientation and direction discrimination thresholds, as well as contrast sensitivity. These results support two conclusions: (1) from a practical perspective, complex moving stimuli and double training may be superior training tools for inducing visual recovery in CB, and (2) the cortically blind visual system can relearn to perform a wider range of visual discriminations than predicted by blindsight alone.

Numerous immunohistochemical biomarkers for patients with urothelial bladder cancer have been identified in order to predict their biological behavior. The aim of this present study was to examine the uroplakin III (UPIII) expression in homogenous group of non-muscle invasive bladder cancer and to correlate its value with clinico-pathological characteristics of patients and moreover with COX-2 expression and tumor infiltrating lymphocytes (TILs). Tumor specimens from 127 patients with non-muscle invasive bladder cancer, divided into two groups: patients who developed recurrent disease during the first five post-operative years (N = 78) and patients without recurrent disease during a follow-up of minimum 5 years (N = 49), were retrieved for tissue microarrays construction. On paraffin sections, the immunohistochemical analysis of UPIII expression was performed and staining was semiquantitatively evaluated. Expression of UPIII, including luminal, membranous and cytoplasmic one, was found in more than half of the tumors (57%). Specific staining pattern for UPIII was not associated with age and gender of patients, pathological grade, tumor size, disease stage or recurrence of disease. There was no association between UPIII, COX-2 and TILs, except for a negative moderate association between UP and COX-2 in the group of patients without recurrent tumor, and a strong association between UPIII and in the group with tumor recurrence. The present work gives an insight into the very complex mechanisms involved in tumor biology and progression. Moreover, it highlights the importance of further studies that should include multiple molecular markers in models designed to predict the outcome of non-muscle invasive bladder cancer.

Actions can be understood based on form cues (e.g., static body posture) as well as motion cues (e.g., gait patterns). A fundamental debate centers on the question of whether the functional and neural mechanisms processing these two types of cues are dissociable. Here, using fMRI, psychophysics, and transcranial magnetic stimulation (TMS), all within the same human participants, we show that mechanisms underlying body form and body motion processing are functionally and neurally distinct. Multivoxel fMRI activity patterns in the extrastriate body area (EBA), but not in the posterior superior temporal sulcus (pSTS), carried cue invariant information about the body form of an acting human. Conversely, multivoxel patterns in pSTS, but not in EBA, carried information about the body motion of the same actor. In a psychophysical experiment, we selectively impaired body form and body motion discriminations by manipulating different visual cues: misaligning the ellipses that made up a dynamic walker stimulus selectively disrupted body form discriminations, while varying the presentation duration of the walker selectively affected body motion discriminations. Finally, a TMS experiment revealed causal evidence for a double-dissociation between neural mechanisms underlying body form and body motion discriminations: TMS over EBA selectively disrupted body form discrimination, whereas TMS over pSTS selectively disrupted body motion discrimination. Together, these findings reveal complementing but dissociable functions of EBA and pSTS during action perception. They provide constraints for theoretical and computational models of action perception by showing that action perception involves at least two parallel pathways that separately contribute to the understanding of others' behavior.

Angiotensinogen (AGT) is the precursor of active vasoconstrictive octapeptide angiotensin II (Ang II) in the renin-angiotensin-aldosterone system. Blocking the AGT-converting enzymes in the pathway and the Ang II receptor through pharmacological agents has been proven to be effective in lowering blood pressure (BP) in hypertensive patients. In this study, we developed chemically modified small interfering RNAs (siRNA) to target hepatic AGT mRNA in rats. Lipid nanoparticle encapsulated siRNAs were efficiently delivered to rat liver and resulted in significant reduction in hepatic Agt mRNA levels and plasma AGT concentration without impairing liver function. Single intravenous injection of Agt siRNA led to significant and sustained BP lowering in spontaneous hypertensive rats and in Sprague-Dawley rats, and the effect was maintained by weekly siRNA dosing. Data presented here provide proof-of-feasibility for the use of siRNA technology for inhibition of peripheral AGT levels via hepatic mRNA silencing with beneficial effects on BP in preclinical rat models. Similar approach could be used for validation of novel hypertension hepatic and extrahepatic targets.

Self-generated body movements have reliable visual consequences. This predictive association between vision and action likely underlies modulatory effects of action on visual processing. However, it is unknown whether actions can have generative effects on visual perception. We asked whether, in total darkness, self-generated body movements are sufficient to evoke normally concomitant visual perceptions. Using a deceptive experimental design, we discovered that waving one’s own hand in front of one’s covered eyes can cause visual sensations of motion. Conjecturing that these visual sensations arise from multisensory connectivity, we showed that grapheme-color synesthetes experience substantially stronger kinesthesis-induced visual sensations than nonsynesthetes do. Finally, we found that the perceived vividness of kinesthesis-induced visual sensations predicted participants’ ability to smoothly track self-generated hand movements with their eyes in darkness, which indicates that these sensations function like typical retinally driven visual sensations. Evidently, even in the complete absence of external visual input, the brain predicts visual consequences of actions.

SummaryEarly psychologists, including Galton, Cattell, and Spearman, proposed that intelligence and simple sensory discriminations are constrained by common neural processes, predicting a close link between them [1, 2]. However, strong supporting evidence for this hypothesis remains elusive. Although people with higher intelligence quotients (IQs) are quicker at processing sensory stimuli [1–5], these broadly replicated findings explain a relatively modest proportion of variance in IQ. Processing speed alone is, arguably, a poor match for the information processing demands on the neural system. Our brains operate on overwhelming amounts of information [6, 7], and thus their efficiency is fundamentally constrained by an ability to suppress irrelevant information [8–21]. Here, we show that individual variability in a simple visual discrimination task that reflects both processing speed and perceptual suppression [22] strongly correlates with IQ. High-IQ individuals, although quick at perceiving small moving objects, exhibit disproportionately large impairments in perceiving motion as stimulus size increases. These findings link intelligence with low-level sensory suppression of large moving patterns—background-like stimuli that are ecologically less relevant [22–25]. We conjecture that the ability to suppress irrelevant and rapidly process relevant information fundamentally constrains both sensory discriminations and intelligence, providing an information-processing basis for the observed link.

Visual input is remarkably diverse. Certain sensory inputs are more probable than others, mirroring statistical regularities of the visual environment. The visual system exploits many of these regularities, resulting, on average, in better inferences about visual stimuli. However, by incorporating prior knowledge into perceptual decisions, visual processing can also result in perceptions that do not match sensory inputs. Such perceptual biases can often reveal unique insights into underlying mechanisms and computations. For example, a prior assumption that objects move slowly can explain a wide range of motion phenomena. The prior on slow speed is usually rationalized by its match with visual input, which typically includes stationary or slow moving objects. However, this only holds for foveal and parafoveal stimulation. The visual periphery tends to be exposed to faster motions, which are biased toward centrifugal directions. Thus, if prior assumptions derive from experience, peripheral motion processing should be biased toward centrifugal speeds. Here, in experiments with human participants, we support this hypothesis and report a novel visual illusion where stationary objects in the visual periphery are perceived as moving centrifugally, while objects moving as fast as 7°/s toward fovea are perceived as stationary. These behavioral results were quantitatively explained by a Bayesian observer that has a strong centrifugal prior. This prior is consistent with both the prevalence of centrifugal motions in the visual periphery and a centrifugal bias of direction tuning in cortical area MT, supporting the notion that visual processing mirrors its input statistics.

Dental composite materials come into direct contact with oral tissue, especially gingival cells. This study was performed to evaluate possible DNA-damage to gingival cells exposed to resin composite dental materials. Class V restorations were placed in 30 adult patients using two different composite resins. The epithelial cells of the gingival area along the composite restoration were sampled prior to and after 7 days, 30 days, and 180 days following the restoration of the tooth. DNA damage was analysed by comet and micronucleus assays in gingival exfoliated epithelial cells. The results showed significantly higher comet assay parameters (tail length and % DNA in the tail) within periods of 30 and 180 days. The micronucleus test for the same exposure time demonstrated a higher number of cells with micronuclei, karyolysis, and nuclear buds. Results did not reveal any difference between the two composite materials for the same duration of exposure. Based on the results, we can conclude that the use of composite resins causes cellular damage. As dental composite resins remain in intimate contact with oral tissue over a long period of time, further research on their possible genotoxicity is advisable. Clinical Relevance: Long-term exposure of gingival cells to two different composite materials demonstrated certain DNA damage. However, considering the significant decline in micronuclei frequency after 180 days and efficiency in the repair of primary DNA damage, the observed effects could not be indicated as biologically relevant.

Visual function demands coordinated responses to information over a wide field of view, involving both central and peripheral vision. Visually impaired individuals often seem to underutilize peripheral vision, even in absence of obvious peripheral deficits. Motivated by perceptual training studies with typically sighted adults, we examined the effectiveness of perceptual training in improving peripheral perception of visually impaired youth. Here, we evaluated the effectiveness of three training regimens: (1) an action video game, (2) a psychophysical task that combined attentional tracking with a spatially and temporally unpredictable motion discrimination task, and (3) a control video game. Training with both the action video game and modified attentional tracking yielded improvements in visual performance. Training effects were generally larger in the far periphery and appear to be stable 12 months after training. These results indicate that peripheral perception might be under-utilized by visually impaired youth and that this underutilization can be improved with only ~8 hours of perceptual training. Moreover, the similarity of improvements following attentional tracking and action video-game training suggest that well-documented effects of action video-game training might be due to the sustained deployment of attention to multiple dynamic targets while concurrently requiring rapid attending and perception of unpredictable events.

Background SREBP cleavage-activating protein (SCAP) is a cholesterol binding endoplasmic reticulum (ER) membrane protein that is required to activate SREBP transcription factors. SREBPs regulate genes involved in lipid biosynthesis. They also influence lipid clearance by modulating the expression of LDL receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Inhibiting SCAP decreases circulating PCSK9, triglycerides (TG), and LDL-cholesterol (LDL-C), both in vitro and in vivo. Type 2 diabetics with dyslipidemia are at high risk for cardiovascular diseases. These patients present a unique pathophysiological lipid profile characterized by moderately elevated LDL-C, elevated TG and reduced HDL-cholesterol (HDL-C). The spontaneous dysmetabolic rhesus monkey model (DysMet RhM) recapitulates this human dyslipidemia and therefore is an attractive preclinical model to evaluate SCAP inhibition as a therapy for this disease population. The objective to of this study was to assess the effect of SCAP inhibition on the lipid profile of DysMet RhM. Method We assessed the effect of inhibiting hepatic SCAP on the lipid profile of DysMet RhM using an siRNA encapsulated lipid nanoparticle (siRNA-LNP). Results The SCAP siRNA-LNP significantly reduced LDL-C, PCSK9 and TG in DysMet RhM; LDL-C was reduced by ≥ 20%, circulating PCSK9 by 30–40% and TG by > 25%. These changes by the SCAP siRNA-LNP agree with the predicted effect of SCAP inhibition and reduced SREBP tone on these endpoints. Conclusion These data demonstrate that a SCAP siRNA-LNP improved the lipid profile in a clinically relevant preclinical disease model and provide evidence for SCAP inhibition as a therapy for diabetic dyslipidemic patients.

ObjectivesTo examine the cognitive and neural effects of vision-based speed-of-processing (VSOP) training in older adults with amnestic mild cognitive impairment (aMCI) and contrast those effects with an active control (mental leisure activities (MLA)).DesignRandomized single-blind controlled pilot trial.SettingAcademic medical center.ParticipantsIndividuals with aMCI (N=21).InterventionSix-week computerized VSOP training.MeasurementsMultiple cognitive processing measures, instrumental activities of daily living (IADLs), and two resting state neural networks regulating cognitive processing: central executive network (CEN) and default mode network (DMN).ResultsVSOP training led to significantly greater improvements in trained (processing speed and attention: F1,19 =6.61, partial η(2) =0.26, P=.02) and untrained (working memory: F1,19 =7.33, partial η(2) =0.28, P=.01; IADLs: F1,19 =5.16, partial η(2) =0.21, P=.03) cognitive domains than MLA and protective maintenance in DMN (F1, 9 =14.63, partial η(2) =0.62, P=.004). VSOP training, but not MLA, resulted in a significant improvement in CEN connectivity (Z=-2.37, P=.02).ConclusionTarget and transfer effects of VSOP training were identified, and links between VSOP training and two neural networks associated with aMCI were found. These findings highlight the potential of VSOP training to slow cognitive decline in individuals with aMCI. Further delineation of mechanisms underlying VSOP-induced plasticity is necessary to understand in which populations and under what conditions such training may be most effective.

A 48-year-old man residing in a mental health department inpatient program with a history of schizoaffective disorder presented to the emergency department with a chief complaint of fever and intense abdominal pain for one day. The patient stated he initially fell in the shower and afterwards experienced back pain. He was transferred to an acute care unit within the facility for further evaluation. The facility physician noted that the patient had a mild temperature elevation and abdominal rigidity on exam. At that time, he was given two doses of benztropine intramuscularly, and transferred to our hospital for further evaluation. The patient exhibited fever, diffuse abdominal pain and a nonproductive cough, but denied chills, dysuria, urinary frequency, hematuria, weakness, diarrhea, melena or hematochezia. He did have a one-week history of constipation for which he was given sodium phosphate enemas, magnesium citrate and docusate sodium, eventually resulting in a bowel movement. He also complained of new onset dysphagia. There were no recent changes to his medications, which included clonazepam, divalproex sodium extended release, olanzapine and risperidone. He denied use of tobacco, alcohol or illicit drugs.

Microsomal triglyceride transfer protein (Mtp) inhibitors represent a novel therapeutic approach to lower circulating LDL cholesterol, although therapeutic development has been hindered by the observed increase in hepatic triglycerides and liver steatosis following treatment. Here, we used small interfering RNAs (siRNA) targeting Mtp to achieve target-specific silencing to study this phenomenon and to determine to what extent liver steatosis is induced by changes in Mtp expression. We observed that Mtp silencing led to a decrease in many genes involved in hepatic triglyceride synthesis. Given the role of diacylglycerol O-acyltransferase 2 (Dgat2) in regulating hepatic triglyceride synthesis, we then evaluated whether target-specific silencing of both Dgat2 and Mtp were sufficient to attenuate Mtp silencing-induced liver steatosis. We showed that the simultaneous inhibition of Dgat2 and Mtp led to a decrease in plasma cholesterol and a reduction in the accumulation of hepatic triglycerides caused by the inhibition of Mtp. Collectively, these findings provide a proof-of-principle for a triglyceride synthesis/Mtp inhibitor combination and represent a potentially novel approach for therapeutic development in which targeting multiple pathways can achieve the desired response.

Objectives were to investigate histopathologic findings, placental diameters and characteristics of syncytial knots in the placentas from idiopathic intrauterine growth retardation (IUGR) pregnancies, and to compare them with a normal birth weight group. Based on strict eligibility criteria, this prospective case–control study included 52 term placentas from idiopathic IUGR pregnancies and 69 term placentas from normal birth weight pregnancies. The study was carried out at the Clinical Hospital Centre, Split, where all placentas were collected and examined. For each placenta, diameters were measured and the following histopathologic findings were recorded: infarction, intervillous thrombosis, abruption, villous branching and maturation, chorioamnionitis, decidual vasculopathy and hemorrhagic endovasculitis for each placenta. In addition we assessed quantitative (number of syncytial knots and number of syncytial nuclei per syncytial knot) and qualitative (density and surface area) characteristics of syncytial knots in each placental sample. Statistical significance was tested using χ2-test, Student's t-test and Mann–Whitney U-test. Statistical significance was set at P≤0.05. There was no difference in investigated histopathologic findings between idiopathic IUGR placentas and control group placentas. Placental diameters correlated significantly with neonatal birth weight (r=0.64 ; P

This report aims at exploring quantitatively the relationship between FXII inhibition and thromboprotection. FXII full and partial null in rats were established via zinc finger nuclease-mediated knockout and siRNA-mediated knockdown, respectively. The rats were subsequently characterized in thrombosis and hemostasis models. Knockout rats exhibited complete thromboprotection in both the arteriovenous shunt model (∼100% clot weight reduction) and the FeCl3-induced arterial thrombosis model (no reduction in blood flow), without any increase in cuticle bleeding time compared with wild-type control rats. Ex-vivo aPTT and the ellagic acid-triggered thrombin generation assay (TGA) exhibited anticoagulant changes. In contrast, ex-vivo PT or high tissue factor-triggered TGA was indistinguishable from control. Rats receiving single doses (0, 0.01, 0.03, 0.1, 0.3, 1 mg/kg) of FXII siRNA exhibited dose-dependent knockdown in liver FXII mRNA and plasma FXII protein (95 and 99%, respectively, at 1 mg/kg) at day 7 post dosing. FXII knockdown was associated with dose-dependent thromboprotection (maximal efficacy achieved with 1 mg/kg in both models) and negligible change in cuticle bleeding times. Ex-vivo TGA triggered with low-level (0.5 μmol/l) ellagic acid tracked best with the knockdown levels and efficacy. Our findings confirm and extend literature reports of an attractive benefit-to-risk profile of targeting FXII for antithrombotic therapies. Titrating of FXII is instructive for its pharmacological inhibition. The knockout rat is valuable for evaluating both mechanism-based safety concerns and off-target effects of FXII(a) inhibitors. Detailed TGA analyses will inform on optimal trigger conditions in studying pharmacodynamic effects of FXII(a) inhibition.

Visual phenomena demonstrating striking perceptual disappearances of salient stimuli have fascinated researchers because of their utility in identifying neural processes that underlie subjective visibility and invisibility. Motion-induced blindness (MIB) is appealing for such purposes because it, like a class of ostensibly related paradigms such as binocular rivalry, features periods of unequivocal subjective disappearances despite constant physical stimulation. It remains unclear, however, exactly how the mechanisms that cause MIB are related to subjectively observed fluctuations in visual awareness. To address this question, we used continuous flash suppression (CFS) to present the MIB stimulus outside visual awareness. Results indicated that MIB occasionally reappeared from suppression with its salient yellow target absent. To quantify this observation, we measured reaction times (RTs) to detect the yellow dot target following visible or perceptually suppressed MIB and indeed found no difference in RTs between these conditions. We also provide evidence that MIB fluctuations can occur without attention. In sum, these experiments indicate that MIB fluctuations are effectively changes in stimulus strength, which under typical conditions result in unmistakable subjective disappearances, but are not inherently fluctuations in stimulus visibility. More broadly, these results challenge the assumed privileged link between bistable stimuli and visual awareness.

Attentional influence over perception is particularly pronounced when sensory stimulation is ambiguous, where attention can reduce stimulus uncertainty and promote a stable interpretation of the world. However, binocular rivalry, an extensively studied visual ambiguity, has proved to be comparatively resistant to attentional modulation. We hypothesize that this apparent inconsistency reflects fluctuations in the degree of unresolved competition during binocular rivalry. Namely, attentional influence over rivalry dynamics should be limited to phases of relatively unresolved stimulus competition, such as ends of individual dominance periods. We found that transient, feature-based cues congruent with the dominant stimulus prolonged dominance durations, while cues matching the suppressed stimulus hastened its return to dominance. Notably, the effect of cues depended on when the cues are presented. Cues presented late, but not early, during a given episode of perceptual dominance influenced rivalry dynamics. This temporal pattern mirrors known changes in the relative competitive dynamics of rival stimuli, revealing that selective effects occur only during temporal windows containing weak resolution of visual competition. In conclusion, these findings reveal that unresolved competition, which gates attention across a variety of domains, is also crucial in determining the susceptibility of binocular rivalry to selective influences.

For audiovisual sensory events, sound arrives with a delay relative to light that increases with event distance. It is unknown, however, whether humans can use these ubiquitous sound delays as an information source for distance computation. Here, we tested the hypothesis that audiovisual delays can both bias and improve human perceptual distance discrimination, such that visual stimuli paired with auditory delays are perceived as more distant and are thereby an ordinal distance cue. In two experiments, participants judged the relative distance of two repetitively displayed three-dimensional dot clusters, both presented with sounds of varying delays. In the first experiment, dot clusters presented with a sound delay were judged to be more distant than dot clusters paired with equivalent sound leads. In the second experiment, we confirmed that the presence of a sound delay was sufficient to cause stimuli to appear as more distant. Additionally, we found that ecologically congruent pairing of more distant events with a sound delay resulted in an increase in the precision of distance judgments. A control experiment determined that the sound delay duration influencing these distance judgments was not detectable, thereby eliminating decision-level influence. In sum, we present evidence that audiovisual delays can be an ordinal cue to visual distance.

Lipoprotein(a) [Lp(a)] has recently been recognized as an independent risk factor for coronary heart disease. While plasma Lp(a) levels are correlated with cardiovascular risk, the mechanism by which this particle contributes to atherosclerosis is largely unknown. Although humanized transgenic mouse model has recently been described to study Lp(a) biology, non-human primates (NHP) are the only preclinical model available that allow study of the role of Lp(a) in atherosclerosis in an innate setting. We describe targeting of LPA using lipid nanoparticle formulated short interfering RNAs (siRNAs) in lean rhesus macaque monkeys. We show >90 % LPA mRNA lowering in the liver and >95 % Lp(a) plasma reduction for over 3 weeks after a single siRNA dose. Given the potency of LPA siRNAs, siRNA approach may enable chronic reduction of Lp(a) in atherosclerotic NHP and help to unmask the role for Lp(a) in the genesis and progression of atherosclerosis in man.

SummaryHaemophilia A and B are characterised by a life-long bleeding predisposition, and several lines of evidence suggest that risks of atherothrombotic events may also be reduced. Establishing a direct correlation between coagulation factor levels, thrombotic risks and bleeding propensity has long been hampered by an inability to selectively and specifically inhibit coagulation factor levels. Here, the exquisite selectivity of gene silencing combined with a gene knockout (KO) approach was used to define the relative contribution of factor IX (fIX) to thrombosis and primary haemostasis in the rat. Using a lipid nanoparticle (LNP) formulation, we successfully delivered fIX siRNAs to the liver by intravenous administration. The knockdown (KD) of target gene mRNA was achieved rapidly (within 24 hour post-siRNA dosing), sustained (maintained for at least 7 days post dosing) and not associated with changes in mRNA expression levels of other coagulation factors. We found that intermediate levels of liver fIX mRNA silencing (60–95 %) translating into a 50–99 % reduction of plasma fIX activity provided protection from thrombosis without prolonging the cuticle bleeding time. Over 99 % inhibition of fIX activity was required to observe increase in bleeding, a phenotype confirmed in fIX KO rats. These data provide substantial evidence of a participation of fIX in the mechanisms regulating thrombosis prior to those regulating primary haemostasis, therefore highlighting the potential of fIX as a therapeutic target. In addition, hepatic mRNA silencing using LNP-encapsulated siRNAs may represent a promising novel approach for the chronic treatment and prevention of coagulation-dependent thrombotic disorders in humans.

Occasional doubts about the real effect of the prostate volume on the urinary discomforts that elderly have been experiencing required additional assessment of these parameters. The aim of this study was to re- evaluate relationship between the urinary discomforts of the elderly and the prostate volume in comparison with age. Results of the group of 79 patients observed within one-year period were analyzed. In assessing their urinary discomforts the International Prostate Symptom Score (IPSS) was calculated, the ultrasound prostate volumetry was performed, and both of these parameters where compared with age. Statistical analysis of the results confi rmed signifi cant positive correlation between the prostate volume and age, positive correlation between IPSS and age, as well as between prostate volume and IPSS.

X-linked congenital generalized hypertrichosis (Online Mendelian Inheritance in Man 307150) is an extremely rare condition of hair overgrowth on different body sites. We previously reported linkage in a large Mexican family with X-linked congenital generalized hypertrichosis cosegregating with deafness and with dental and palate anomalies to Xq24-27. Using SNP oligonucleotide microarray analysis and whole-genome sequencing, we identified a 389-kb interchromosomal insertion at an extragenic palindrome site at Xq27.1 that completely cosegregates with the disease. Among the genes surrounding the insertion, we found that Fibroblast Growth Factor 13 ( FGF13 ) mRNA levels were significantly reduced in affected individuals, and immunofluorescence staining revealed a striking decrease in FGF13 localization throughout the outer root sheath of affected hair follicles. Taken together, our findings suggest a role for FGF13 in hair follicle growth and in the hair cycle.

People with intellectual disability (ID) usually have a poor quality of oral health, which include poor oral hygiene, untreated caries and high proportion of missing teeth. Due to their fear and repulsive attitude towards medical staff, general anesthesia is often a useful method for dental treatment. One thousand and fifty four intellectual disability patients for the period of 1985–2009 who received dental treatment under general anesthesia in Dental Polyclinic Split, were included in the study. Patients were divided into five groups based upon the period when a specific dental treatment had been received. Each period was analyzed for the number of ID patients treated and the type of dental treatment. The results showed that the most services provided were 4006 fillings, followed by 3225 extracted teeth and finally 274 endodontic treatments. Significantly the lowest number of fillings and endodontic treatments were found among patients in group II (1990–1994), with significantly the highest number of extracted teeth. In Conclusion, the types of dental treatment have changed during twenty five years. Number of extracted teeth decreased while the number of fillings and endodontic treatment increased. However, dental status of people with intellectual disability should be improved with more restorative treatments and with better oral health prevention program.