Biomarkers and neuromodulation techniques in substance use disorders

Addictive disorders are a severe health concern. Conventional therapies have just moderate success and the probability of relapse after treatment remains high. Brain stimulation techniques, such as transcranial Direct Current Stimulation (tDCS) and Deep Brain Stimulation (DBS), have been shown to be effective in reducing subjectively rated substance craving. However, there are few objective and measurable parameters that reflect neural mechanisms of addictive disorders and relapse. Key electrophysiological features that characterize substance related changes in neural processing are Event-Related Potentials (ERP). These high temporal resolution measurements of brain activity are able to identify neurocognitive correlates of addictive behaviours. Moreover, ERP have shown utility as biomarkers to predict treatment outcome and relapse probability. A future direction for the treatment of addiction might include neural interfaces able to detect addiction-related neurophysiological parameters and deploy neuromodulation adapted to the identified pathological features in a closed-loop fashion. Such systems may go beyond electrical recording and stimulation to employ sensing and neuromodulation in the pharmacological domain as well as advanced signal analysis and machine learning algorithms. In this review, we describe the state-of-the-art in the treatment of addictive disorders with electrical brain stimulation and its effect on addiction-related neurophysiological markers. We discuss advanced signal processing approaches and multi-modal neural interfaces as building blocks in future bioelectronics systems for treatment of addictive disorders

Monitoring of chemical parameters of qualitative pasta samples containing millet flours during storage experiments

Millet has attracted a great deal of interest due to its valuable agricultural, nutritional, and functional properties. In this study the aim was the investigation of millet usability in dry pasta products. Chemical, enzymological, and sensory parameters were measured and monitored in Triticum aestivum, Triticum durum, and millet containing pasta products during a 12-month-long storage period. According to our results, during the storage, millet had a strong effect on different parameters: because of increased acid value, the shelf life was reduced, and millet significantly influenced the pH value and the water soluble polyphenol content. The highest scores were measured in T. durum and T. durum-millet pasta samples in the sensory test, while the T. aestivum-millet mixture pasta got the lowest scores. Also in our experiment we tested how the drying temperature modifies polyphenol oxidase enzyme (PPO) activity right after drying and during storage. The samples containing millet flour had higher PPO activity in all cases after drying, while pasta made with T. durum had the lowest PPO activity. Our results showed that drying temperature has a significant impact on PPO activity

Role of oxygen vacancy defect states in the n-type conduction of β-Ga[sub 2]O[sub 3]

Based on semiempirical quantum-chemical calculations, the electronic band structure of β-Ga2O3 is presented and the formation and properties of oxygen vacancies are analyzed. The equilibrium geometries and formation energies of neutral and doubly ionized vacancies were calculated. Using the calculated donor level positions of the vacancies, the high temperature n-type conduction is explained. The vacancy concentration is obtained by fitting to the experimental resistivity and electron mobility

Face-Fusion of Icosahedral Boron Hydride Increases Affinity to γ‐Cyclodextrin: closo,closo‐[B₂₁H₁₈]⁻ as an Anion with Very Low Free Energy of Dehydration

[Abstract] The supramolecular recognition of closo,closo‐[B₂₁H₁₈]⁻ by cyclodextrins (CDs) has been studied in aqueous solution by isothermal titration calorimetry and nuclear magnetic resonance spectroscopy. These solution studies follow up on previous mass‐spectrometric measurements and computations, which indicated the formation and stability of CD ⋅ B₂₁H₁₈⁻ complexes in the gas phase. The thermodynamic signature of solution‐phase binding is exceptional, the association constant for the γ‐CD complex with B₂₁H₁₈⁻ reaches 1.8×10⁶ M⁻¹, which is on the same order of magnitude as the so far highest observed value for the complex between γ‐CD and a metallacarborane. The nature of the intermolecular interaction is also examined by quantum‐mechanical computational protocols. These suggest that the desolvation penalty, which is particularly low for the B₂₁H₁₈⁻ anion, is the decisive factor for its high binding strength. The results further suggest that the elliptical macropolyhedral boron hydride is another example of a CD binder, whose extraordinary binding affinity is driven by the chaotropic effect, which describes the intrinsic affinity of large polarizable and weakly solvated chaotropic anions to hydrophobic cavities and surfaces in aqueous solution.K.I.A. and W.M.N. are grateful to the DFG for grant NA-686/8 within the priority program SPP 1807 “Control of London Dispersion Interactions in Molecular Chemistry”. J.H., J.F., and D.H. thank the Czech Science Foundation (grant number 17-08045S) and M.I.F.P., M.C.L, and J.A.S.L. thank the regional government Xunta de Galicia for financial support (Project Grupo Potencial Crecemento -GPC- ED431B 2017/59). J.M.O.-E. acknowledges financial support from the Spanish MICINN through project CTQ2018-094644-B-C22German Research Foundation; NA‐686/8Czech Science Foundation; 17‐08045SXunta de Galicia; ED431B 2017/5

Pyruvate carboxylase deficiency type C; variable presentation and beneficial effect of triheptanoin

Pyruvate carboxylase is a mitochondrial enzyme essential for the tricarboxylic acid cycle (TCA), gluconeogenesis and fatty-acid synthesis. Pyruvate carboxylase deficiency (PCD) mostly presents with life-limiting encephalopathy (types A/B). A milder type C presentation is rare, with a comparatively favourable prognosis. Therapies remain essentially supportive. Triheptanoin is an odd-chain triglyceride, with the potential to replenish TCA intermediates (anaplerosis), and its metabolites cross the blood–brain-barrier. Outcomes of triheptanoin treatment in PCD types A/B have been disappointing, but have not been reported in type C. Here, we present two new patients with PCD type C, and report the response to treatment with triheptanoin in one. Patient 1 (P1) presented with neonatal-onset lactic acidosis and recurrent symptomatic lactic acidosis following exercise and during illnesses, with frequent hospitalisations. Speech development was delayed. MRI-brain showed delayed cerebral myelination. Patient 2 (P2) presented with episodic ketoacidosis, hyperlactataemia and hypoglycaemia at 2 years of age, with gross motor delay and mild global volume loss on MRI brain. Treatment with triheptanoin was commenced in P1 at 3 years of age with up-titration to 35 mL/day (25% of daily energy intake) over 6 months, due to transient diarrhoea. Dietary long-chain triglycerides were restricted, with fat-soluble vitamin supplementation. Subsequently, hospitalisations during intercurrent illnesses decreased, post-exertional hyperlactataemia resolved and exercise tolerance improved. Continued developmental progress was observed, and repeat MRI 18 months after initiation showed improved myelination. Triheptanoin was well-tolerated and appeared efficacious during 2 years' follow-up, and has potential to restore energy homeostasis and myelin synthesis in PCD type C

AVERT2(a very early rehabilitation trial, a very effective reproductive trigger): retrospective observational analysis of the number of babies born to trial staff

Objective: To report the number of participants needed to recruit per baby born to trial staff during AVERT, a large international trial on acute stroke, and to describe trial management consequences. Design: Retrospective observational analysis. Setting: 56 acute stroke hospitals in eight countries. Participants: 1074 trial physiotherapists, nurses, and other clinicians. Outcome measures: Number of babies born during trial recruitment per trial participant recruited. Results: With 198 site recruitment years and 2104 patients recruited during AVERT, 120 babies were born to trial staff. Births led to an estimated 10% loss in time to achieve recruitment. Parental leave was linked to six trial site closures. The number of participants needed to recruit per baby born was 17.5 (95% confidence interval 14.7 to 21.0); additional trial costs associated with each birth were estimated at 5736 Australian dollars on average. Conclusion: The staff absences registered in AVERT owing to parental leave led to delayed trial recruitment and increased costs, and should be considered by trial investigators when planning research and estimating budgets. However, the celebration of new life became a highlight of the annual AVERT collaborators’ meetings and helped maintain a cohesive collaborative group

“Not Tied Up Neatly with a Bow”: Professionals’ Challenging Cases in Informed Consent for Genomic Sequencing

As the use of genomic technology has expanded in research and clinical settings, issues surrounding informed consent for genome and exome sequencing have surfaced. Despite the importance of informed consent, little is known about the specific challenges that professionals encounter when consenting patients or research participants for genomic sequencing. We interviewed 29 genetic counselors and research coordinators with considerable experience obtaining informed consent for genomic sequencing to understand their experiences and perspectives. As part of this interview, 24 interviewees discussed an informed consent case they found particularly memorable or challenging. We analyzed these case examples to determine the primary issue or challenge represented by each case. Challenges fell into two domains: participant understanding, and facilitating decisions about testing or research participation. Challenges related to participant understanding included varying levels of general and genomic literacy, difficulty managing participant expectations, and contextual factors that impeded participant understanding. Challenges related to facilitating decision-making included complicated family dynamics such as disagreement or coercion, situations in which it was unclear whether sequencing research would be a good use of participant time or resources, and situations in which the professional experienced disagreement or discomfort with participant decisions. The issues highlighted in these case examples are instructive in preparing genetics professionals to obtain informed consent for genomic sequencing

Diverging asymmetry of intrinsic functional organization in autism

Autism is a neurodevelopmental condition involving atypical sensory-perceptual functions together with language and socio-cognitive deficits. Previous work has reported subtle alterations in the asymmetry of brain structure and reduced laterality of functional activation in individuals with autism relative to non-autistic individuals (NAI). However, whether functional asymmetries show altered intrinsic systematic organization in autism remains unclear. Here, we examined inter- and intra-hemispheric asymmetry of intrinsic functional gradients capturing connectome organization along three axes, stretching between sensory-default, somatomotor-visual, and default-multiple demand networks, to study system-level hemispheric imbalances in autism. We observed decreased leftward functional asymmetry of language network organization in individuals with autism, relative to NAI. Whereas language network asymmetry varied across age groups in NAI, this was not the case in autism, suggesting atypical functional laterality in autism may result from altered developmental trajectories. Finally, we observed that intra- but not inter-hemispheric features were predictive of the severity of autistic traits. Our findings illustrate how regional and patterned functional lateralization is altered in autism at the system level. Such differences may be rooted in atypical developmental trajectories of functional organization asymmetry in autism

The 293 K structure of tetradehydrohaliclonacyclamine A

The polycyclic title compound {systematic name: (1S,16S,17S,31S)-3,20- diaza-tetra-cyclo-[15.15.0.1.1] tetra-tria-conta-6,8,23,25-tetra-ene}, CHN , has recently been isolated and characterized structurally, in solution by NMR spectroscopy and in the solid state by X-ray crystallography. At 130 K the structure is monoclinic (P21, Z = 4) and comprises two mol-ecules in the asymmetric unit with distinctly different conformations in the twelve-C-atom bridging chains. We report that, at 250 K, a phase change from monoclinic to ortho-rhom-bic (P22121, Z = 4) occurs. The higher-temperature phase is structurally characterized herein at 293 K. The two different conformers resolved in the monoclinic low-temperature form merge to give a single disordered mol-ecule in the asymmetric unit of the high-temperature phase

Angular Forces Around Transition Metals in Biomolecules

Quantum-mechanical analysis based on an exact sum rule is used to extract an semiclassical angle-dependent energy function for transition metal ions in biomolecules. The angular dependence is simple but different from existing classical potentials. Comparison of predicted energies with a computer-generated database shows that the semiclassical energy function is remarkably accurate, and that its angular dependence is optimal.Comment: Tex file plus 4 postscript figure