Sleep in autism: A biomolecular approach to aetiology and treatment.

People with autism spectrum disorder (ASD) commonly experience other comorbidities. Studies indicate that between 50% and 83% of individuals with ASD have sleep problems or disorders. The most commonly reported sleep problems are: (a) insomnia symptoms including the inability to get to sleep or stay asleep; and (b) circadian rhythm sleep-wake disorders, defined as a misalignment between the timing of endogenous circadian rhythms and the external environment. The circadian system provides timing information for the sleep-wake cycle that is regulated by the interaction of an endogenous processes (circadian - Process C, and homeostatic - Process S) and synchronizing agents (neurohormones and neurotransmitters), which produce somnogenic activity. A clinical priority in ASD is understanding the cause of these sleep problems in order to improve treatment outcomes. This review approaches sleep in autism from several perspectives: Sleep-wake mechanisms and problems, and brain areas and molecules controlling sleep (e.g., GABA and melatonin) and wake maintenance (e.g., serotonin, acetylcholine and glutamate). Specifically, this review examines how altered sleep structure could be related to neurobiological alterations or genetic mutations and the implications this may have for potential pharmacological treatments in individuals with ASD.

Who attempts suicide among medical students?

OBJECTIVE: To identify factors associated with a history of suicide attempt in medical students. METHODS: A Web-based survey was sent out to a sample of medical students. A multi-predictor Poisson regression was performed to identify factors associated with a history of suicide attempt. In addition, an elastic net regularization was used to build a risk calculator to identify students at risk for attempted suicide. RESULTS: A total of 4,840 participants were included in the study. Prevalence of suicide attempts in the sample was 8.94%. Risk factors associated with past suicide attempt in the multi-predictor Poisson regression were as follows: female gender (P < 0.001); homosexuality (P < 0.001); low income (P = 0.026); bullying by university peers (P = 0.006); childhood (P = 0.001) or adult (P = 0.001) trauma; family history of suicide (P = 0.005); suicidal ideation within the last month (P < 0.001); daily tobacco use (P = 0.037); and being at severe risk for alcohol abuse (P = 0.023). Our elastic net model performed well with an AUC of 0.83. CONCLUSIONS: This study identifies a number of key factors associated with a history of suicide attempts among medical students. Future longitudinal studies should assess the causal relationship between these factors and suicide attempts. Additionally, these results demonstrate that current available data on suicide attempts among medical students can be used to develop an accurate risk algorithm.

Efficient hydrogen bonding recognition in water using aryl-extended calix[4]pyrrole receptors.

We describe the synthesis of four water-soluble aryl-extended calix[4]pyrrole receptors and report their binding properties with multiple neutral polar guests in water. The prepared receptors present different functionalization at their upper rims and have in common the placement of water solubilizing pyridinium groups at their lower rims. We investigate the interaction of the receptors with a guest series in water solution using 1H NMR titrations and ITC experiments. Despite the known competitive nature of water for hydrogen-bonding interactions, we demonstrate the formation of thermodynamically highly stable 1 : 1 inclusion complexes stabilized by hydrogen-bonding interactions. We show that increasing the hydrogen-bond acceptor character of the guest has a positive impact on binding affinity. This result suggests that the receptor's cavity is indeed a better hydrogen-bond donor to interact with the guests than water molecules. We also assess the important contribution of the hydrophobic effect to binding by comparing the binding affinities of analogous inclusion complexes in water and chloroform solutions. The more polar guests are bound with similar affinities in the two solvents. We compare the binding properties of the different complexes in order to derive general trends.

Conformational selectivity and high-affinity binding in the complexation of N-phenyl amides in water by a phenyl extended calix[4]pyrrole.

We describe the synthesis of a tetrapyridinium phenyl extended calix[4]pyrrole that is soluble in neutral water solution at mM concentrations. We show that, in pure water, the synthesized calix[4]pyrrole receptor selectively binds the cis-(E) conformers of secondary N-phenyl-amides and tertiary N-methyl-N-phenyl-formamide with binding affinities larger than 103 M-1. The conformational selectivity is remarkable owing to the energetic preference of amides to adopt the trans-(Z) conformation in solution. In this respect, we used two binding models for the mathematical analyses of the titration data and calculated apparent and intrinsic binding constants. The combined action of hydrogen bonding and the hydrophobic effect that operates in the binding of the amides in water is responsible for the large affinities displayed by the receptor.

A Stochastic Spiking Neural Network for Virtual Screening.

Virtual screening (VS) has become a key computational tool in early drug design and screening performance is of high relevance due to the large volume of data that must be processed to identify molecules with the sought activity-related pattern. At the same time, the hardware implementations of spiking neural networks (SNNs) arise as an emerging computing technique that can be applied to parallelize processes that normally present a high cost in terms of computing time and power. Consequently, SNN represents an attractive alternative to perform time-consuming processing tasks, such as VS. In this brief, we present a smart stochastic spiking neural architecture that implements the ultrafast shape recognition (USR) algorithm achieving two order of magnitude of speed improvement with respect to USR software implementations. The neural system is implemented in hardware using field-programmable gate arrays allowing a highly parallelized USR implementation. The results show that, due to the high parallelization of the system, millions of compounds can be checked in reasonable times. From these results, we can state that the proposed architecture arises as a feasible methodology to efficiently enhance time-consuming data-mining processes such as 3-D molecular similarity search.

Clinical parameters of implants placed in healed sites using flapped and flapless techniques: A systematic review.

BACKGROUND: Dental implant placement using flapless surgery is a minimally invasive technique that improves blood supply compared with flapped surgery. However, the flapless technique does not provide access to allow bone regeneration. OBJECTIVE: The aim of this systematic review was to evaluate the clinical parameters following implant surgery in healed sites, using two procedures: flapped vs. flapless surgery. MATERIALS AND METHODS: A detailed electronic search was carried out in the PubMed/Medline, Embase and Cochrane Library databases. The focused question was, "How do flapped and flapless surgical techniques affect the clinical parameters of dental implants placed in healed sites?". All the studies included with a prospective controlled design were considered separately, depending on whether they had been conducted on animals or humans. The following data were recorded in all the included studies: number of implants, failures, location (maxilla, mandible), type of rehabilitation (partial or single), follow-up and flap design. The variables selected for comparison in the animal studies were the following: flap design, gingival index, mucosal height, recession and probing pocket depth. In humans studies the variables were as follows: flap design, plaque index, gingival index, recession, probing pocket depth, papilla index and keratinized gingiva. RESULTS: Ten studies were included, six were experimental studies and four were clinical studies. Studies in animals showed better results using the flapless technique in the parameters analyzed. There is no consensus in the clinical parameters analyzed in human studies, but there is a trend to better results using flapless approach. CONCLUSION: The animal studies included in the present review show that implants placed in healed sites with a flapless approach have better clinical parameters than the flapped procedure in a short-term follow-up. In human studies, there is no consensus about which technique offer better results in terms of clinical parameters. Therefore, more research in humans is required in order to overcome the limitations and contrast these results.

Preservation of electronic properties of double-decker complexes on metallic supports.

Single-molecule magnets based on lanthanide double-deckers are attracting significant attention due to their unrivaled single-ion anisotropy. To exploit their fascinating electronic and magnetic properties in devices for information storage or spin transport, studies on the preservation or variation of electronic and magnetic functionalities upon adsorption on surfaces are necessary. Herein, we introduced a comprehensive scanning tunneling microscopy (STM) and X-ray photoelectron spectroscopy (XPS) surface science study, complemented by density functional theory (DFT) simulations, of a recently synthesized single-molecule magnet based on porphyrazine deckers, conveniently equipped with ethyl moieties to make them soluble and sublimable. We demonstrated that the double-decker species were intactly adsorbed on Au(111), Ag(111), and Cu(111) in a flat-on fashion and self-assembled in hexagonal close-packed layers. Systematic multi- and monolayer XPS was performed on the surface-confined species, confirming the preservation of the electronic properties of the ligands and the lanthanide center upon adsorption.

Persistence of slow dynamics in Tb(OETAP)2 single molecule magnets embedded in conducting polymers.

UNLABELLED: The spin dynamics of Tb(OETAP)2 single ion magnets was investigated by means of muon spin relaxation (µSR) both in the bulk material as well as when the molecule is embedded into PEDOT: PSS polymer conductor. The spin fluctuation time is characterized by a high temperature activated trend, with an energy barrier around 320 K, and by a low temperature tunneling regime. When the single ion magnet is embedded into the polymer the energy barrier only slightly decreases and the fluctuation time remains of the same order of magnitude, even at low temperature. This finding shows that these single molecule magnets preserve their characteristics which, if combined with those of the conducting polymer, result in a hybrid material of potential interest for organic spintronics.

Water-soluble aryl-extended calix[4]pyrroles with unperturbed aromatic cavities: synthesis and binding studies.

We report the synthesis of a novel, water-soluble aryl-extended calix[4]pyrrole receptor. The water-solubilising groups are placed at the lower rim of the receptor, leaving the binding pocket unperturbed and open for modification. Binding studies were performed with a series of pyridine N-oxides. These studies revealed the ability of the receptor to bind neutral and charged N-oxides in basified water with stability constants higher than 10(4) M(-1).

Selective binding of cis-1,3,5-cyclohexane tricarboxylic acid vs its epimeric trans isomer by a tripodal amidopyridine receptor; crystal structures of the 1:1 complexes.

[figure: see text] A tripodal tris-amidopyridine receptor forms a 1:1 complex with trans-1,3,5-cyclohexane tricarboxylic acid that is 1 order of magnitude less stable than the one formed with the corresponding cis-triacid epimer. The X-ray crystal structures of the complexes have been determined, confirming the binding geometry derived from NMR data in solution and force-field calculations, and its geometrical features are used to explain the observed selectivity.

An Effective Fluorescent Sensor for Choline-Containing Phospholipids.

A set of weak CH small middle dot small middle dot small middle dotO interactions is responsible for the recognition of tetraalkylammonium ions (ball-and-stick structure) by the tripodal receptors depicted in the diagram, in which the binding pocket is lined with squaramide units. The association constants of the fluorescent receptors are remarkably high at about 10(5) M(-1) and can be used for signaling the presence of selected choline phospholipids. Z=RNH, where R=alkyl, arylamino; X(-)=BH(4)(-), Cl(-), Br(-), I(-).

[The narrow lumbar canal. Study of a surgical series of 139 cases]. / Canaux lombaires étroits. Etude d'une série opératoire de 139 cas.

Over a period of 9 years, 139 patients with a mean age of 61 years were operated upon for disorders due to narrow lumbar vertebral canal. Clinical expression varied: lumbago, movement sciatica, intermittent claudication... Importance must be attached to discordance of examination findings in apparently benign root pain (67% of cases). The two key examinations of radiologic investigation are radiculography and a CT scan. Treatment is surgical, generally by a two-stage wide laminectomy combined with abrasion of an articular facet (64%), excision of osteophytic pads (35%) and/or treatment for a soft herniated disc (26%). Recovery was obtained in 35% of cases and pronounced improvement in 49% (84% of very good and good results) as evaluated by patients and surgeons.