Speckle filtering through nonlinear wave mixing.

Light scattering by disordered media is a ubiquitous effect. After passing through them, the light acquires a random phase, masking or destroying associated information. Filtering this random phase is of paramount importance to many applications, such as sensing, imaging, and optical communication, to cite a few, and it is commonly achieved through computationally extensive post-processing using statistical correlation. In this work, we show that mixing noisy optical modes of various complexity in a second-order nonlinear medium can be used for efficient and straightforward filtering of a random wavefront under sum-frequency generation processes without utilizing correlation-based calculations.

Intervertebral disc decellularisation: progress and challenges.

Intervertebral disc (IVD) degeneration and the consequent low-back pain (LBP) affect over 80 % of people in western societies, constituting a tremendous socio-economic burden worldwide and largely impairing patients' life quality. Extracellular matrix (ECM)-based scaffolds, derived from decellularised tissues, are being increasingly explored in regenerative medicine for tissue repair. Decellularisation plays an essential role for host cells and antigen removal, while maintaining native microenvironmental signals, including ECM structure, composition and mechanical properties, which are essential for driving tissue regeneration. With the lack of clinical solutions for IVD repair/regeneration, implantation of decellularised IVD tissues has been explored to halt and/or revert the degenerative cascade and the associated LBP symptoms. Over the last few years, several researchers have focused on the optimisation of IVD decellularisation methods, combining physical, chemical and enzymatic treatments, in order to successfully develop a cell-free matrix. Recellularisation of IVD-based scaffolds with different cell types has been attempted and numerous methods have been explored to address proper IVD regeneration. Herein, the advances in IVD decellularisation methods, sterilisation procedures, repopulation and biocompatibility tests are reviewed. Additionally, the importance of the donor profile for therapeutic success is also addressed. Finally, the perspectives and major hurdles for clinical use of the decellularised ECM-based biomaterials for IVD are discussed. The studies reviewed support the notion that tissue-engineering-based strategies resorting to decellularised IVD may represent a major advancement in the treatment of disc degeneration and consequent LBP.

Suitable state bases for nonlinear optical mode conversion protocols.

By considering parity-defined Laguerre-Gaussian (LG) and Hermite-Gaussian (HG) beams as input modes, we present arguments through experimental and theoretical results in order to affirm that using HG modes as bases is more suitable for optical mode conversion than using LG modes. By analyzing the normalized overlap integral and the generated modes, we determine a clear rule for the dominant mode for nonlinear mixing of HG beams, while the same is not possible for LG beams. In addition, examples of optical modal conversion using both HG and LG modes as input beams are demonstrated.

Energetic and thermodynamical aspects of the cyclodextrins-cannabidiol complex in aqueous solution: a molecular-dynamics study.

Cyclodextrins (CDs) are well-known carriers for encapsulating hydrophobic molecules, while among cannabinoids, cannabidiol (CBD) has attracted considerable attention due to its therapeutic capability. In this framework, we employed molecular dynamics and docking techniques for investigating the interaction energy and thermodynamical issues between different CDs (α, ß, and γ type) and CBD immersed in water and a solution mimicking a physiological environment. We quantified the energetic aspects, for different thermal conditions, in which both aqueous solutions interact with CBDs and CDs and the CBD-CDs complex itself. In order to approximate the physiological conditions, our simulations also included the mammalian temperature. The calculations revealed significant interaction energy between lactate and the CD surface and a movement of lactate toward CD as well. We observed an almost constant number of lactate molecules forming clusters without exhibiting a temperature dependence. Next, the degree of CBD-CDs complexation at four different temperatures was analyzed. The results showed that the complexation depends on the medium, becoming weaker with the temperature increment. Our findings highlighted that the entropy contribution is relevant for CBD-α-CD and CBD-ß-CD, while CBD-γ-CD is practically insensitive to temperature changes for both solutions. In both water and artificial physiological solutions, the γ-CD appears more stable than the other complexes. Overall, CBD achieved partial encapsulation considering α-CD and ß-CD, showing a temperature dependence, while γ-CD remained fully immersed no matter the thermal level assumed. We also discuss the pharmacological relevance and physiological implications of these findings.

The effect of school intervention programs on the body mass index of adolescents: a systematic review with meta-analysis.

Effective obesity interventions in adolescent populations have been identified as an immediate priority action to stem the increasing prevalence of adult obesity. The purpose of this meta-analysis was to make a quantitative analysis of the impact of school-based interventions on body mass index during adolescence. Studies were retrieved from PubMed, Scopus, Science Direct and Web of Science databases. Results were pooled using a random-effects model with 95% confidence interval considered statistically significant. Of the 18 798 possible relevant articles identified, 12 articles were included in this meta-analysis. The global result showed a low magnitude effect, though it was statistically significant (N = 14 428), global e.s. = -0.055, P = 0.004 (95% CI = -0.092, -0.017). Heterogeneity was low among the studies (I2 = 9.017%). The funnel plot showed no evidence of publication bias. The rank-correlation test of Begg (P = 0.45641) and Egger's regression (P = 0.19459) confirmed the absence of bias. This meta-analysis reported a significant effect favoring the interventions; however, future research are needed since the reported the evidence was of low magnitude, with the studies following a substantial range of approaches and mostly had a modest methodological quality.

Molecular and cellular mechanisms of learning disabilities: a focus on NF1.

Neurofibromatosis Type I (NF1) is a single-gene disorder characterized by a high incidence of complex cognitive symptoms, including learning disabilities, attention deficit disorder, executive function deficits, and motor coordination problems. Because the underlying genetic cause of this disorder is known, study of NF1 from a molecular, cellular, and systems perspective has provided mechanistic insights into the etiology of higher-order cognitive symptoms associated with the disease. In particular, studies of animal models of NF1 indicated that disruption of Ras regulation of inhibitory networks is critical to the etiology of cognitive deficits associated with NF1. Animal models of Nf1 identified mechanisms and pathways that are required for cognition, and represent an important complement to the complex neuropsychological literature on learning disabilities associated with this condition. Here, we review findings from NF1 animal models and human populations affected by NF1, highlighting areas of potential translation and discussing the implications and limitations of generalizing findings from this single-gene disease to idiopathic learning disabilities.

Memory allocation mechanisms underlie memory linking across time.

Memories are dynamic in nature. A cohesive representation of the world requires memories to be altered over time, linked with other memories and eventually integrated into a larger framework of sematic knowledge. Although there is a considerable literature on how single memories are encoded, retrieved and updated, little is known about the mechanisms that govern memory linking, e.g., linking and integration of various memories across hours or days. In this review, we present evidence that specific memory allocation mechanisms, such as changes in CREB and intrinsic excitability, ensure memory storage in ways that facilitate effective recall and linking at a later time. Beyond CREB and intrinsic excitability, we also review a number of other phenomena with potential roles in memory linking.

Aqueous solution interactions with sex hormone-binding globulin and estradiol: a theoretical investigation.

Sex hormone-binding globulin (SHBG) is a binding protein that regulates the availability of steroid hormones in the plasma. Although best known as a steroid carrier, recent studies have associated SHBG in modulating behavioral aspects related to sexual receptivity. Among steroids, estradiol (17ß-estradiol, oestradiol or E2), documented as the most active endogenous female hormone, exerts important physiological roles in both reproductive and non-reproductive functions. In this framework, we employed molecular dynamics (MD) and docking techniques for quantifying the interaction energy between a complex aqueous solution, composed by different salts, SHBG and E2. As glucose concentration resembles measured levels in diabetes, special emphasis was devoted to analyzing the interaction energy between this carbohydrate, SHBG and E2 molecules. The calculations revealed remarkable interaction energy between glucose and SHBG surface. Surprisingly, a movement of solute components toward SHBG was observed, yielding clusters surrounding the protein. The high energy and short distance between glucose and SHBG suggests a possible scenario in favor of a detainment state between the sugar and the protein. In this context, we found that glucose clustering does not insert modification on binding site area nor over binding energy SHBG-E2 complex, in spite of protein superficial area increment. The calculations also point to a more pronounced interaction between E2 and glucose, considering the hormone immersed in the solution. In summary, our findings contribute to a better comprehension of both SHBG and E2 interplay with aqueous solution components.

Correction to: Statistical crossover and nonextensive behavior of neuronal short-term depression.

The authors apologize for the following errors published in the article. However, these errors do not modify the main assumptions in our work nor affects the discussion (interpretation) of the results.

Statistical crossover and nonextensive behavior of neuronal short-term depression.

The theoretical basis of neuronal coding, associated with short-term degradation in synaptic transmission, is a matter of debate in the literature. In fact, electrophysiological signals are commonly characterized as inversely proportional to stimulus intensity. Among theoretical descriptions of this phenomenon, models based on 1/f-dependency are employed to investigate the biophysical properties of short-term synaptic depression. In this work, we formulate a model based on a paradigmatic q-differential equation to obtain a generalized formalism useful for investigation of nonextensivity in this specific type of synaptic plasticity. Our analysis reveals nonextensivity in data from electrophysiological recordings and also a statistical crossover in neurotransmission. In particular, statistical transitions provide additional support to the hypothesis of heterogeneous release probability of neurotransmitters. On the other hand, the simple vesicle model agrees with data only at low-frequency stimulations. Thus, the present work presents a method to demonstrate that short-term depression is not only governed by random mechanisms but also by nonextensive behavior. Our findings also conciliate morphological and electrophysiological investigations into a coherent biophysical scenario.

HCN channels are a novel therapeutic target for cognitive dysfunction in Neurofibromatosis type 1.

Cognitive impairments are a major clinical feature of the common neurogenetic disease neurofibromatosis type 1 (NF1). Previous studies have demonstrated that increased neuronal inhibition underlies the learning deficits in NF1, however, the molecular mechanism underlying this cell-type specificity has remained unknown. Here, we identify an interneuron-specific attenuation of hyperpolarization-activated cyclic nucleotide-gated (HCN) current as the cause for increased inhibition in Nf1 mutants. Mechanistically, we demonstrate that HCN1 is a novel NF1-interacting protein for which loss of NF1 results in a concomitant increase of interneuron excitability. Furthermore, the HCN channel agonist lamotrigine rescued the electrophysiological and cognitive deficits in two independent Nf1 mouse models, thereby establishing the importance of HCN channel dysfunction in NF1. Together, our results provide detailed mechanistic insights into the pathophysiology of NF1-associated cognitive defects, and identify a novel target for clinical drug development.

Maximum-likelihood q-estimator uncovers the role of potassium at neuromuscular junctions.

Recently, we demonstrated the existence of nonextensive behavior in neuromuscular transmission (da Silva et al. in Phys Rev E 84:041925, 2011). In this letter, we first obtain a maximum-likelihood q-estimator to calculate the scale factor ([Formula: see text]) and the q-index of q-Gaussian distributions. Next, we use the indexes to analyze spontaneous miniature end plate potentials in electrophysiological recordings from neuromuscular junctions. These calculations were performed assuming both normal and high extracellular potassium concentrations [Formula: see text]. This protocol was used to test the validity of Tsallis statistics under electrophysiological conditions closely resembling physiological stimuli. The analysis shows that q-indexes are distinct depending on the extracellular potassium concentration. Our letter provides a general way to obtain the best estimate of parameters from a q-Gaussian distribution function. It also expands the validity of Tsallis statistics in realistic physiological stimulus conditions. In addition, we discuss the physical and physiological implications of these findings.

2013 multistate outbreaks of Cyclospora cayetanensis infections associated with fresh produce: focus on the Texas investigations.

The 2013 multistate outbreaks contributed to the largest annual number of reported US cases of cyclosporiasis since 1997. In this paper we focus on investigations in Texas. We defined an outbreak-associated case as laboratory-confirmed cyclosporiasis in a person with illness onset between 1 June and 31 August 2013, with no history of international travel in the previous 14 days. Epidemiological, environmental, and traceback investigations were conducted. Of the 631 cases reported in the multistate outbreaks, Texas reported the greatest number of cases, 270 (43%). More than 70 clusters were identified in Texas, four of which were further investigated. One restaurant-associated cluster of 25 case-patients was selected for a case-control study. Consumption of cilantro was most strongly associated with illness on meal date-matched analysis (matched odds ratio 19·8, 95% confidence interval 4·0-∞). All case-patients in the other three clusters investigated also ate cilantro. Traceback investigations converged on three suppliers in Puebla, Mexico. Cilantro was the vehicle of infection in the four clusters investigated; the temporal association of these clusters with the large overall increase in cyclosporiasis cases in Texas suggests cilantro was the vehicle of infection for many other cases. However, the paucity of epidemiological and traceback information does not allow for a conclusive determination; moreover, molecular epidemiological tools for cyclosporiasis that could provide more definitive linkage between case clusters are needed.

Hydrodynamic profile of young swimmers: changes over a competitive season.

The aim of this study was to analyze the changes in the hydrodynamic profile of young swimmers over a competitive season and to compare the variations according to a well-designed training periodization. Twenty-five swimmers (13 boys and 12 girls) were evaluated in (a) October (M1); (b) March (M2); and (c) June (M3). Inertial and anthropometrical measures included body mass, swimmer's added water mass, height, and trunk transverse surface area. Swimming efficiency was estimated by the speed fluctuation, stroke index, and approximate entropy. Active drag was estimated with the velocity perturbation method and the passive drag with the gliding decay method. Hydrodynamic dimensionless numbers (Froude and Reynolds numbers) and hull velocity (i.e., speed at Froude number = 0.42) were also calculated. No variable presented a significant gender effect. Anthropometrics and inertial parameters plus dimensionless numbers increased over time. Swimming efficiency improved between M1 and M3. There was a trend for both passive and active drag increase from M1 to M2, but being lower at M3 than at M1. Intra-individual changes between evaluation moments suggest high between- and within-subject variations. Therefore, hydrodynamic changes over a season occur in a non-linear fashion way, where the interplay between growth and training periodization explain the unique path flow selected by each young swimmer.

Transmission of Balamuthia mandrillaris through solid organ transplantation: utility of organ recipient serology to guide clinical management.

A liver, heart, iliac vessel and two kidneys were recovered from a 39-year-old man who died of traumatic head injury and were transplanted into five recipients. The liver recipient 18 days posttransplantation presented with headache, ataxia and fever, followed by rapid neurologic decline and death. Diagnosis of granulomatous amebic encephalitis was made on autopsy. Balamuthia mandrillaris infection was confirmed with immunohistochemical and polymerase chain reaction (PCR) assays. Donor and recipients' sera were tested for B. mandrillaris antibodies. Donor brain was negative for Balamuthia by immunohistochemistry and PCR; donor serum Balamuthia antibody titer was positive (1:64). Antibody titers in all recipients were positive (range, 1:64-1:512). Recipients received a four- to five-drug combination of miltefosine or pentamidine, azithromycin, albendazole, sulfadiazine and fluconazole. Nausea, vomiting, elevated liver transaminases and renal insufficiency were common. All other recipients survived and have remained asymptomatic 24 months posttransplant. This is the third donor-derived Balamuthia infection cluster described in solid organ transplant recipients in the United States. As Balamuthia serologic testing is only available through a national reference laboratory, it is not feasible for donor screening, but may be useful to determine exposure status in recipients and to help guide chemotherapy.

Gestational immune activation and Tsc2 haploinsufficiency cooperate to disrupt fetal survival and may perturb social behavior in adult mice.

Approximately 40-50% of individuals affected by tuberous sclerosis (TSC) develop autism spectrum disorders (ASDs). One possible explanation for this partial penetrance is an interaction between TSC gene mutations and other risk factors such as gestational immune activation. In this study, we report the interactive effects of these two ASD risk factors in a mouse model of TSC. Combined, but not single, exposure had adverse effects on intrauterine survival. Additionally, provisional results suggest that these factors synergize to disrupt social approach behavior in adult mice. Moreover, studies in human populations are consistent with an interaction between high seasonal flu activity in late gestation and TSC mutations in ASD. Taken together, our studies raise the possibility of a gene × environment interaction between heterozygous TSC gene mutations and gestational immune activation in the pathogenesis of TSC-related ASD.

The interaction between intra-cyclic variation of the velocity and mean swimming velocity in young competitive swimmers.

The aim of this study was to assess the relationship between the intra-cyclic variation of the horizontal velocity (dv) and the velocity of the 4 competitive swimming techniques in young swimmers. 45 young swimmers performed a set of maximal 4 × 25 m (freestyle, backstroke, breaststroke and butterfly stroke) swims with in water start. A speed-meter cable was attached to the swimmer's hip. The dv and the swimming velocity were analyzed. Within-subject tests presented significant variations in the dv based on the swimming technique. Post-hoc test revealed significant differences across all pair-wised swimming techniques (P<0.001), except for the comparison between freestyle and backstroke (P=0.98). The dv was higher in the breaststroke, followed by the butterfly, the backstroke and the freestyle. The quadratic models had the best goodness-of-fit and the lower error of estimation for the relationship between the dv and the swimming velocity in all swimming techniques (0.24 ≤ R(2) ≤ 0.51). As a conclusion, there is a non-linear relationship where the increase of swimming velocity leads to a decrease of dv in young competitive swimmers.

Effects of swim training on energetics and performance.

The aim of this study was to determine the effect of several months of training on performance and energetic profile of elite swimmers. 9 elite swimmers were evaluated at 3 different time periods during the 2010-2011 calendar. Swimming performance was assessed based on lists of times for the 200 m freestyle event. An incremental set of 7×200 m swims was applied to obtain the energetic data. Measurements and/or estimations were made for the: velocity at 4 mmol l(-1) of lactate concentrations, highest value of lactate concentrations, maximal oxygen consumption, minimum swimming velocity where the maximal oxygen consumption is reached and total energy expenditure (Etot). The performance and most of the energetic variables assessed presented no significant variations during the study period. The only exception was the Etot with significant differences between all measurements. Correlation coefficients suggested a high stability for all variables. Cohen's Kappa tracking index demonstrated high variability in the individual adaptations to training. It is concluded that elite swimmers demonstrate a slight improvement in performance and energetic profile in response to several months of training. Each subject has an individual way of adapting to the training load, combining the different energetic confounders to enhance performance.

A mouse model for the learning and memory deficits associated with neurofibromatosis type I.

Neurofibromatosis type I (NF1) is one of the most commonly inherited neurological disorders in humans, affecting approximately one in 4,000 individuals. NF1 results in a complex cluster of developmental and tumour syndromes that include benign neurofibromas, hyperpigmentation of melanocytes and hamartomas of the iris. Some NF1 patients may also show neurologic lesions, such as optic pathway gliomas, dural ectasia and aqueduct stenosis. Importantly, learning disabilities occur in 30% to 45% of patients with NF1, even in the absence of any apparent neural pathology. The learning disabilities may include a depression in mean IQ scores, visuoperceptual problems and impairments in spatial cognitive abilities. Spatial learning has been assessed with a variety of cognitive tasks and the most consistent spatial learning deficits have been observed with the Judgement of Line Orientation test. It is important to note that some of these deficits could be secondary to developmental abnormalities and other neurological problems, such as poor motor coordination and attentional deficits. Previous studies have suggested a role for neurofibromin in brain function. First, the expression of the Nf1 gene is largely restricted to neuronal tissues in the adult. Second, this GTPase activating protein may act as a negative regulator of neurotrophin-mediated signalling. Third, immunohistochemical studies suggest that activation of astrocytes may be common in the brain of NF1 patients. Here, we show that the Nf1+/- mutation also affects learning and memory in mice. As in humans, the learning and memory deficits of the Nf1+/- mice are restricted to specific types of learning, they are not fully penetrant, they can be compensated for with extended training, and they do not involve deficits in simple associative learning.

Learning deficits, but normal development and tumor predisposition, in mice lacking exon 23a of Nf1.

Neurofibromatosis type 1 (NF1) is a commonly inherited autosomal dominant disorder. Previous studies indicated that mice homozygous for a null mutation in Nf1 exhibit mid-gestation lethality, whereas heterozygous mice have an increased predisposition to tumors and learning impairments. Here we show that mice lacking the alternatively spliced exon 23a, which modifies the GTPase-activating protein (GAP) domain of Nf1, are viable and physically normal, and do not have an increased tumor predisposition, but show specific learning impairments. Our findings have implications for the development of a treatment for the learning disabilities associated with NF1 and indicate that the GAP domain of NF1 modulates learning and memory.