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Corticotropin-releasing factor (CRF) regulates the stress response in the hypothalamus and modulates neurotransmission across the brain through CRF receptors. Acute stress increases hypothalamic CRF and the GABAergic neurosteroid (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP). We previously showed that 3α,5α-THP regulation of CRF is sex and brain region dependent. In this study, we investigated 3α,5α-THP regulation of stress-induced hypothalamic CRF, CRF receptor type 1 (CRFR1), CRF binding protein (CRFBP), pro-opiomelanocortin (POMC), and glucocorticoid receptor (GR) by western blot and circulating corticosterone (CORT) by enzyme-linked immunosorbent assay (ELISA) in male and female Sprague Dawley rats. Tissue was collected after rats were injected with 3α,5α-THP (15 mg/kg, IP) or vehicle 15 min prior to 30 min of restraint stress (RS), or 10 min of forced swim stress (FSS) and 20 min recovery. The initial exposure to a stress stimulus increased circulating CORT levels in both males and females, but 3α,5α-THP attenuated the CORT response only in females after RS. 3α,5α-THP reduced GR levels in male and females, but differently between stressors. 3α,5α-THP decreased the CRF stress response after FSS in males and females, but after RS, only in female rats. 3α,5α-THP reduced the CRFR1, CRFBP, and POMC increases after RS and FSS in males, but in females only after FSS. Our results showed different stress responses following different types of stressors: 3α,5α-THP regulated the HPA axis at different levels, depending on sex.

Introduction: The therapeutic management of women with epilepsy (WWE) of childbearing age can be complicated by the need to balance maternal/fetal risks related to seizure occurrence during gestation with the potential teratogenic risks related to the use of anti-seizure medications (ASMs)., Areas Covered: The authors review clinical evidence on seizure-related and ASM-related risks during pregnancy. Current regulatory indications are discussed, evaluating their impact on clinical practice, and ethical implications of pharmacological decisions are debated., Expert Opinion: If properly informed about the maternal/fetal risks carried by different pharmacological choices, WWE can become the final decision makers regarding their care in every phase of their life. Over the coming years, analysis of aggregated pregnancy registry data on the structural impact, on the fetus, of low doses of valproate and of newer ASMs, together with analysis of the main population study data on functional (cognitive and behavioral) outcomes, could lead to huge advances, making choosing an ASM a less complex process for the clinician and a less painful decision for the woman. Future objectives should include identification of the potential role of the pharmacogenomic profile of WWE in determining the risk of fetal malformations.

Background and Purpose: We sought to investigate whether there are gender differences in clinical outcome after stroke due to large vessel occlusion (LVO) after mechanical thrombectomy (EVT) in a large population of real-world patients., Methods: From the Italian Registry of Endovascular Thrombectomy, we extracted clinical and outcome data of patients treated for stroke due to large vessel occlusion. We compared clinical and safety outcomes in men and women who underwent EVT alone or in combination with intravenous thrombolysis (IVT) in the total population and in a Propensity Score matched set., Results: Among 3422 patients included in the study, 1801 (52.6%) were women. Despite older age at onset (mean 72.4 vs 68.7; p  < 0.001), and higher rate of atrial fibrillation (41.7% vs 28.6%; p  < 0.001), women had higher probability of 3-month functional independence (adjusted odds ratio-adjOR 1.19; 95% CI 1.02-1.38), of complete recanalization (adjOR 1.25; 95% CI 1.09-1.44) and lower probability of death (adjOR 0.75; 95% CI 0.62-0.90). After propensity-score matching, a well-balanced cohort comprising 1150 men and 1150 women was analyzed, confirming the same results regarding functional outcome (3-month functional independence: OR 1.25; 95% CI 1.04-1.51), and complete recanalization (OR 1.29; 95% CI 1.09-1.53)., Conclusions: Subject to the limitations of a non-randomized comparison, women with stroke due to LVO treated with mechanical thrombectomy had a better chance to achieve complete recanalization, and 3-month functional independence than men. The results could be driven by women who underwent combined treatment., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MB: Consultant for Penumbra Inc., Stryker Italia; AS: Consultant for Stryker; ADV: Consultant for Boehringer Ingelheim, Daichi Sankyo; AZ: speaker fees and consulting fees from Boehringer-Ingelheim, Medtronic, Cerenovus and advisory board from Daiichi Sankyo and Boehringer-Ingelheim and Stryker; MC: speaker fees and consulting fees from Daiichi Sankyo and Bristol Myers Squibb, advisory board from Boehringer-Ingelheim; NPN: Consultant for Penumbra Inc., Acandis GmbH; SS: personal fees and non-financial support from Allergan, Abbott, Eli Lilly, Novartis, TEVA, participation to Advisory Board for Astra Zeneca, and research support from Laborest; AM: Consultant for Boehringer Ingelheim, DR: Proctor for Penumbra. Other Authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors., (© European Stroke Organisation 2022.)

Glass-like carbon (GC) is a nongraphitizing material composed entirely of carbon atoms produced from selected organic polymer resins by controlled pyrolysis in an inert atmosphere. The GC properties are a combination of the properties of glass, ceramic, and graphite, including hardness, low density, low thermal conductivity, high chemical inertness, biocompatibility, high electrical conductivity, and microfabrication process compatibility. Despite these unique properties, the application of GC in mechanical sensors has not been explored thus far. Here, we investigate the electrical, structural, and chemical properties of GC thin films derived from epoxy-based negative photoresist SU-8 pyrolyzed from 700 to 900 °C. In addition, we fabricated microGC piezoresistors pyrolyzed at 700 and 900 °C and integrated them into nonpyrolyzed SU-8 cantilevers to create microelectromechanical systems (MEMS) mechanical sensors. The sensitivities of the GC sensor to strain, force, surface stress, and acceleration are characterized to demonstrate their potential and limits for electromechanical microdevices., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2022.)

The resolving power, chemical sensitivity and non-invasive nature of NMR have made it an established technique for in vivo studies of large organisms both for research and clinical applications. NMR would clearly be beneficial for analysis of entities at the microscopic scale of about 1 nL (the nanoliter scale), typical of early development of mammalian embryos, microtissues and organoids: the scale where the building blocks of complex organisms could be observed. However, the handling of such small samples (about 100 µm) and sensitivity issues have prevented a widespread adoption of NMR. In this article we show how these limitations can be overcome to obtain NMR spectra of a mammalian embryo in its early stage. To achieve this we employ ultra-compact micro-chip technologies in combination with 3D-printed micro-structures. Such device is packaged for use as plug & play sensor and it shows sufficient sensitivity to resolve NMR signals from individual bovine pre-implantation embryos. The embryos in this study are obtained through In Vitro Fertilization (IVF) techniques, transported cryopreserved to the NMR laboratory, and measured shortly after thawing. In less than 1 h these spherical samples of just 130-190 µm produce distinct spectral peaks, largely originating from lipids contained inside them. We further observe how the spectra vary from one sample to another despite their optical and morphological similarities, suggesting that the method can further develop into a non-invasive embryo assay for selection prior to embryo transfer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Embedding liquid metals (LMs) into an elastomer is emerging as a promising strategy for stretchable conductors. Existing manufacturing techniques are struggling between spatial resolution and process complexity and are limited to chemically resistant substrates. Here, we report on a hybrid process combining stencil lithography and centrifugal force-assisted patterning of liquid metal for the development of LM-based stretchable conductors. The selective wetting behavior of oxide-removed eutectic gallium-indium (EGaIn) on metal patterns defined by stencil lithography enables micrometer scale LM patterns on an elastomeric substrate. Stencil lithography allows for defining metal regions without harsh chemical treatments, making it suitable for a wide range of substrates. Microscale LM patterns are achieved by efficiently removing the excess material by the centrifugal forces experienced from spinning the substrate. The proposed approach allows for the creation of LM patterns with a line width as small as 2 μm on a stretchable poly(dimethylsiloxane) (PDMS) substrate. The electrical measurement results show that the fabricated EGaIn devices can endure 40% mechanical strain over several thousands of cycles. Furthermore, a stencil design using microbridges is proposed to address the mechanical stability issue in stencil lithography. An EGaIn conductor with a serpentine structure and an interdigitated capacitor are fabricated and characterized. The results demonstrate that the patterned serpentine conductors retain their functionality with applied mechanical strain up to 80%. The performance of the interdigitated capacitors upon applied strain is in good agreement with the theoretical estimation. Finally, we demonstrate our approach also on poly(octamethylene maleate (anhydride) citrate) (POMaC) substrates to broaden the use of the proposed method to not only flexible and stretchable but also biodegradable substrates, opening a way for in vivo transient microsystem engineering. The work presented here provides a versatile and reliable approach for manufacturing stretchable conductors., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Long-term alcohol use results in behavioral deficits including impaired working memory, elevated anxiety, and blunted inhibitory control that is associated with prefrontal cortical (PFC) dysfunction. Preclinical observations demonstrate multiple impairments in GABAergic neurotransmission onto deep-layer principal cells (PCs) in the prelimbic cortex that suggest dependence-related cortical dysfunction is the product of elevated excitability in these cells. Despite accumulating evidence showing alcohol-induced changes in interneuron signaling onto PCs differ between sexes, there is limited data explicitly evaluating sex-specific ethanol effects on excitatory signaling onto deep-layer PCs that may further contribute to deficits in PFC-dependent behaviors. To address this, we conducted electrophysiological and behavioral tests in both male and female Sprague-Dawley rats to evaluate the effects of chronic ethanol exposure. Among our observations, we report a marked enhancement in glutamatergic signaling onto deep-layer PCs in male, but not female, rats after alcohol exposure. This phenomenon was furthermore specific to a sub-class of PC, sub-cortically projecting Type-A cells, and coincided with enhanced anxiety-like behavior, but no observable deficit in working memory. In contrast, female rats displayed alcohol-induced facilitation in working memory performance with no change in expression of anxiety-like behavior. Together, these results suggest fundamental differences in alcohol effects on cell activity, cortical sub-circuits, and PFC-dependent behaviors across male and female rats., (© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Objective: Our goal was to investigate the long-term clinical course of juvenile myoclonic epilepsy (JME) in a cohort of patients and to identify prognostic factors for refractoriness and seizure relapse after anti-seizure medications (ASMs) withdrawal. A literature review is also presented to consolidate and compare our findings with the previously reported cases., Methods: We retrospectively studied a series of patients diagnosed with JME with 15 years or more of evolution. We collected clinical, neurophysiological and neuroimaging data from patients who met defined inclusion and exclusion criteria., Results: Study involved 61 patients (65.5% female) with mean age at study of 37.6 years, and mean age at its outset of 14.8 years. Median follow-up was 31.0 years (mean 28.9, range 15-53). They presented more frequently with a combination of myoclonic and generalized tonic-clonic seizures (GTCS) (65.6%). Sixty-five percent of patients (n = 40) had a 5-year terminal remission with a mean age at last seizure of 27.4 years. Thirty-two percent of seizure-free patients (n = 13) withdrew ASMs: 6 out of 13 had a recurrence of the seizures while 7 remained seizure-free (mean age at ASMs withdrawal 21.0 versus 35.7 years, p < 0.05). In the multivariate model, a high GTCS frequency at onset (p = 0.026) was a prognostic factor of drug resistance., Conclusion: JME is often regarded as a benign epileptic syndrome, although a quarter of the individuals have refractory epilepsy. The possibility of withdrawing ASMs in patients who have been free of seizures over an extended time seems feasible., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

CRF is the main activator of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress. CRF neurons are found mainly in the hypothalamus, but CRF positive cells and CRF1 receptors are also found in extrahypothalamic structures, including amygdala (CeA), hippocampus, NAc and VTA. CRF release in the hypothalamus is regulated by inhibitory GABAergic interneurons and extrahypothalamic glutamatergic inputs, and disruption of this balance is found in stress-related disorders and addiction. (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP), the most potent positive modulator of GABA A receptors, attenuates the stress response reducing hypothalamic CRF mRNA expression and ACTH and corticosterone serum levels. In this study, we explored 3α,5α-THP regulation of hypothalamic and extrahypothalamic CRF mRNA and peptide expression, in male and female Sprague Dawley rats, following vehicle or 3α,5α-THP administration (15 mg/kg). In the hypothalamus, we found sex differences in CRF mRNA expression (females +74%, p < 0.01) and CRF peptide levels (females -71%, p < 0.001). 3α,5α-THP administration reduced hypothalamic CRF mRNA expression only in males (-50%, p < 0.05) and did not alter CRF peptide expression in either sex. In hippocampus and CeA, 3α,5α-THP administration reduced CRF peptide concentrations only in the male (hippocampus -29%, p < 0.05; CeA -62%, p < 0.01). In contrast, 3α,5α-THP injection increased CRF peptide concentration in the VTA of both males (+32%, p < 0.01) and females (+26%, p < 0.01). The results show sex and region-specific regulation of CRF signals and the response to 3α,5α-THP administration. This data may be key to successful development of therapeutic approaches for stress-related disorders and addiction., (Copyright © 2021. Published by Elsevier Ltd.)

Objectives: To compare three commonly used large-bore aspiration catheters in terms of final successful recanalization rate and first-passage successful and complete recanalization rates (the so called "first-passage effect")., Materials and Methods: it is an observational retrospective multicenter study conducted in three Italian high-volume tertiary stroke centers between January 2017 and May 2019. The study population included all consecutive patients with an ischemic stroke due to middle cerebral artery occlusion (M1 segment only) that underwent intra-arterial mechanical thrombectomy with contact aspiration as first-line strategy within 24 hours from symptoms onset., Results: Three hundred twenty-one patients were included in the study. Multivariable logistic regression analysis comparing the three catheters revealed no differences in terms of successful recanalization. Sofia 6 Plus catheter was associated with better first-passage successful recanalization [OR, 9.09; 95% CI, 2.66-31.03] (p<0.001) and first-passage complete recanalization [OR: 3.73; 95% CI: 1.43-9.72] (p=0.007) whereas rt-PA was associated with worse first-passage recanalization [OR: 0.52; 95% CI: 0.29-0.93] (p=0.028)., Conclusions: No differences between the three catheters were reported in terms of successful recanalization. Sofia 6 Plus has proven to be superior in achieving both successful and complete first-passage recanalization. Conversely, rt-PA was found to be a negative predicting factor of first-passage effect., Competing Interests: Declarations of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Intracranial carotid artery occlusion represents an underinvestigated cause of acute ischemic stroke as well as an indication for mechanical thrombectomy. We investigated baseline and procedural characteristics, outcomes and predictors of outcome in patients with acute ischemic stroke secondary to intracranial carotid artery occlusion., Methods: A retrospective analysis of the Italian Registry of Endovascular Treatment in Acute Stroke was performed. Patients with intracranial carotid artery occlusion (infraclinoid and supraclinoid) with or without cervical artery occlusion but with patent intracranial arteries were included. The 3‑month functional independence, mortality, successful reperfusion and symptomatic intracranial hemorrhage were evaluated., Results: Intracranial carotid artery occlusion with patent intracranial arteries was diagnosed in 387 out of 4940 (7.8%) patients. The median age was 74 years and median baseline National Institute of Health Stroke Scale (NIHSS) was 18. Functional independence was achieved in 130 (34%) patients, successful reperfusion in 289 (75%) and symptomatic intracranial hemorrhage in 33 (9%), whereas mortality occurred in 111 (29%) patients. In univariate analysis functional independence was associated with lower age, lower NIHSS at presentation, higher rate of successful reperfusion and lower rate of symptomatic intracranial hemorrhage. Multivariable regression analysis found age (odds ratio, OR:1.03; P = 0.006), NIHSS at presentation (OR: 1.07; P < 0.001), diabetes (OR: 2.60; P = 0.002), successful reperfusion (OR:0.20; P < 0.001) and symptomatic intracranial hemorrhage (OR: 4.17; P < 0.001) as the best independent predictors of outcome., Conclusion: Our study showed a not negligible rate of intracranial carotid artery occlusion with patent intracranial arteries, presenting mostly as severe stroke, with an acceptable rate of 3‑month functional independence. Age, NIHSS at presentation and successful reperfusion were the best independent predictors of outcome.

We have shown that endogenous neurosteroids, including pregnenolone and 3α,5α-THP inhibit toll-like receptor 4 (TLR4) signal activation in mouse macrophages and the brain of alcohol-preferring (P) rat, which exhibits innate TLR4 signal activation. The current studies were designed to examine whether other activated TLR signals are similarly inhibited by 3α,5α-THP. We report that 3α,5α-THP inhibits selective agonist-mediated activation of TLR2 and TLR7, but not TLR3 signaling in the RAW246.7 macrophage cell line. The TLR4 and TLR7 signals are innately activated in the amygdala and NAc from P rat brains and inhibited by 3α,5α-THP. The TLR2 and TLR3 signals are not activated in P rat brain and they are not affected by 3α,5α-THP. Co-immunoprecipitation studies indicate that 3α,5α-THP inhibits the binding of MyD88 with TLR4 or TLR7 in P rat brain, but the levels of TLR4 co-precipitating with TRIF are not altered by 3α,5α-THP treatment. Collectively, the data indicate that 3α,5α-THP inhibits MyD88- but not TRIF-dependent TLR signal activation and the production of pro-inflammatory mediators through its ability to block TLR-MyD88 binding. These results have applicability to many conditions involving pro-inflammatory TLR activation of cytokines, chemokines, and interferons and support the use of 3α,5α-THP as a therapeutic for inflammatory disease.

Local bandgap tuning in two-dimensional (2D) materials is of significant importance for electronic and optoelectronic devices but achieving controllable and reproducible strain engineering at the nanoscale remains a challenge. Here, we report on thermomechanical nanoindentation with a scanning probe to create strain nanopatterns in 2D transition metal dichalcogenides and graphene, enabling arbitrary patterns with a modulated bandgap at a spatial resolution down to 20 nm. The 2D material is in contact via van der Waals interactions with a thin polymer layer underneath that deforms due to the heat and indentation force from the heated probe. Specifically, we demonstrate that the local bandgap of molybdenum disulfide (MoS 2 ) is spatially modulated up to 10% and is tunable up to 180 meV in magnitude at a linear rate of about -70 meV per percent of strain. The technique provides a versatile tool for investigating the localized strain engineering of 2D materials with nanometer-scale resolution.

Performing chemical analysis at the nanoliter (nL) scale is of paramount importance for medicine, drug development, toxicology, and research. Despite the numerous methodologies available, a tool for obtaining chemical information non-invasively is still missing at this scale. Observer effects, sample destruction and complex preparatory procedures remain a necessary compromise. Among non-invasive spectroscopic techniques, one able to provide holistic and highly resolved chemical information in-vivo is nuclear magnetic resonance (NMR). For its renowned informative power and ability to foster discoveries and life-saving applications, efficient NMR at microscopic scales is highly sought after, but so far technical limitations could not match the stringent necessities of microbiology, such as biocompatible handling, ease of use, and high throughput. Here we introduce a novel microsystem, which combines CMOS technology with 3D microfabrication, enabling nL NMR as a platform tool for non-invasive spectroscopy of organoids, 3D cell cultures, and early stage embryos. In this study we show its application to microlivers models simulating non-alcoholic fatty liver disease, demonstrating detection of lipid metabolism dynamics in a time frame of 14 days based on 117 measurements of single 3D human liver microtissues.

We report on four electron paramagnetic resonance sensors for dynamic magnetic field measurements at 36 mT, 100 mT, 360 mT, and 710 mT. The sensors are based on grounded co-planar microwave resonators operating at about 1 GHz and 3 GHz, realized using printed circuit board technology, and on single-chip integrated microwave oscillators operating at about 10 GHz and 20 GHz, realized using complementary metal-oxide-semiconductor technology. The sensors are designed to mark precisely the moment when a time-dependent magnetic field attains a specific value. The trigger from the sensor can be used to preset the output of real-time magnetic field measurement systems, called "B-trains," which are in operation at several large synchrotron installations, including five of the CERN's particle accelerators. We discuss in detail the performance achieved, in particular, the magnetic field resolution that is in the range of 0.1 nT/Hz 1/2 -6 nT/Hz 1/2 . The effects of material anisotropy and temperature are also discussed. Finally, we present a detailed characterization of the sensors with field ramps as fast as 5 T/s and field gradients as strong as 12 T/m.

Atomically thin materials, such as graphene and transition metal dichalcogenides, are promising candidates for future applications in micro/nanodevices and systems. For most applications, functional nanostructures have to be patterned by lithography. Developing lithography techniques for 2D materials is essential for system integration and wafer-scale manufacturing. Here, a thermomechanical indentation technique is demonstrated, which allows for the direct cutting of 2D materials using a heated scanning nanotip. Arbitrarily shaped cuts with a resolution of 20 nm are obtained in monolayer 2D materials, i.e., molybdenum ditelluride (MoTe 2 ), molybdenum disulfide (MoS 2 ), and molybdenum diselenide (MoSe 2 ), by thermomechanically cleaving the chemical bonds and by rapid sublimation of the polymer layer underneath the 2D material layer. Several micro/nanoribbon structures are fabricated and electrically characterized to demonstrate the process for device fabrication. The proposed direct nanocutting technique allows for precisely tailoring nanostructures of 2D materials with foreseen applications in the fabrication of electronic and photonic nanodevices., (© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Integration of the sensitivity-relevant electronics of nuclear magnetic resonance (NMR) and electron spin resonance (ESR) spectrometers on a single chip is a promising approach to improve the limit of detection, especially for samples in the nanoliter and subnanoliter range. Here, we demonstrate the cointegration on a single silicon chip of the front-end electronics of NMR and ESR detectors. The excitation/detection planar spiral microcoils of the NMR and ESR detectors are concentric and interrogate the same sample volume. This combination of sensors allows one to perform dynamic nuclear polarization (DNP) experiments using a single-chip-integrated microsystem having an area of about 2 mm 2 . In particular, we report 1 H DNP-enhanced NMR experiments on liquid samples having a volume of about 1 nL performed at 10.7 GHz(ESR)/16 MHz(NMR). NMR enhancements as large as 50 are achieved on TEMPOL/H 2 O solutions at room temperature. The use of state-of-the-art submicrometer integrated circuit technologies should allow the future extension of the single-chip DNP microsystem approach proposed here up the THz(ESR)/GHz(NMR) region, corresponding to the strongest static magnetic fields currently available. Particularly interesting is the possibility to create arrays of such sensors for parallel DNP-enhanced NMR spectroscopy of nanoliter and subnanoliter samples.

For many years, research from around the world has suggested that the neuroactive steroid (3α,5α)-3-hydroxypregnan-20-one (allopregnanolone or 3α,5α-THP) may have therapeutic potential for treatment of various symptoms of alcohol use disorders (AUDs). In this critical review, we systematically address all the evidence that supports such a suggestion, delineate the etiologies of AUDs that are addressed by treatment with allopregnanolone or its precursor pregnenolone, and the rationale for treatment of various components of the disease based on basic science and clinical evidence. This review presents a theoretical framework for understanding how endogenous steroids that regulate the effects of stress, alcohol, and the innate immune system could play a key role in both the prevention and the treatment of AUDs. We further discuss cautions and limitations of allopregnanolone or pregnenolone therapy with suggestions regarding the management of risk and the potential for helping millions who suffer from AUDs., (© 2019 by the Research Society on Alcoholism.)

For several years, research from around the world has suggested that the neuroactive steroid (3α,5α)-3-hydroxypregnan-20-one (allopregnanolone) may have therapeutic potential for treatment of various stress-related diseases including post-traumatic stress disorder (PTSD), depression, alcohol use disorders (AUDs), as well as neurological and psychiatric conditions that are worsened in the presence of stress, such as multiple sclerosis, schizophrenia, and seizure disorders. In this review, we make the argument that the pleiotropic actions of allopregnanolone account for its ability to promote recovery in such a wide variety of illnesses. Likewise, the allopregnanolone precursors, pregnenolone and progesterone, share many actions of allopregnanolone. Of course, pregnenolone and progesterone lack direct effects on GABA A receptors, but these compounds are converted to allopregnanolone in vivo . This review presents a theoretical framework for understanding how endogenous neurosteroids that regulate 1) γ-aminobutyric acid (GABA) A receptors, 2) corticotropin releasing factor (CRF) and 3) pro-inflammatory signaling in the innate immune system and brain could play a key role in both the prevention and treatment of stress-related disease. We further discuss cautions and limitations of allopregnanolone or precursor therapy as well as the need for more clinical studies., Competing Interests: All other authors report no conflict of interest., (© 2019 The Authors.)

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by changes in social interactions, impaired language and communication, fear responses and presence of repetitive behaviours. Although the genetic bases of ASD are well documented, the recent increase in clinical cases of idiopathic ASD indicates that several environmental risk factors could play a role in ASD aetiology. Among these, maternal exposure to psychosocial stressors during pregnancy has been hypothesized to affect the risk for ASD in offspring. Here, we tested the hypothesis that preconceptional stressful experiences might also represent crucial elements in the aetiology of ASD. We previously showed that social isolation stress during adolescence results in a marked decrease in the brain and plasma concentrations of progesterone and in the quality of maternal care that these female rats later provide to their young. Here we report that male offspring of socially isolated parents showed decreased agonistic behaviour and social transmission of flavour preference, impairment in reversal learning, increased seizure susceptibility, reduced plasma oxytocin levels, and increased plasma and brain levels of BDNF, all features resembling an ASD-like phenotype. These alterations came with no change in spatial learning, aggression, anxiety and testosterone plasma levels, and were sex-dependent. Altogether, the results suggest that preconceptional stressful experiences should be considered as crucial elements for the aetiology of ASD, and indicate that male offspring of socially isolated parents may be a useful animal model to further study the neurobiological bases of ASD, avoiding the adaptations that may occur in other genetic or pharmacologic experimental models of these disorders., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Psychiatric and intellectual comorbidities are common in patients with epilepsy. However, data on the use of antiepileptic drugs in these patients are still lacking. This study assessed the real-world effectiveness and safety/tolerability of eslicarbazepine acetate (ESL) in patients with intellectual disability and psychiatric comorbidities, including a separate analysis specifically in those with depression, using data from the Euro-Esli study. Effectiveness measures included responder and seizure freedom rates. Safety and tolerability were assessed by evaluating adverse events (AEs) and ESL discontinuation due to AEs, respectively. Of the 2058 patients initially included in the Euro-Esli study, 952 patients had intellectual disability data available, 1138 had psychiatric comorbidity data available and 1134 had depression data available. Of those who had intellectual or psychiatric comorbidity data available, 11.3% (108/952) suffered from intellectual disability, 24.9% (283/1138) had a psychiatric disorder, including depression, and 12.4% (141/1134) specifically had depression. Responder and seizure freedom rates were generally comparable between patients with psychiatric comorbidity and those without, and patients with depression and those without. However, responder and seizure freedom rates were significantly lower in patients with intellectual disability compared with those without. Overall, patients with psychiatric and intellectual comorbidities experienced more AEs and AEs leading to ESL discontinuation than patients without these comorbidities. The incidence of psychiatric AEs was not significantly different for patients with psychiatric comorbidities or depression than those without, and the incidence of cognitive AEs was not significantly different for patients with intellectual disability than those without. These findings suggest that ESL is effective in patients with psychiatric and intellectual comorbidities and that its use in these patients is unlikely to exacerbate existing psychiatric or cognitive disturbances., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We report on two ferrimagnetic resonance (FMR) sensors for absolute dynamic magnetic field measurements at 36 and 100 mT. The sensors are designed to mark precisely and reproducibly the moment when a time-transient magnetic field attains a specific value. The trigger from the sensor can then be used for real-time magnetic field measurement systems, called "B-trains," which are in operation at several large synchrotron installations including five of CERN's particle accelerators. We discuss in detail the design, the operation, and the performance of the FMR sensors based on two different types of printed circuit board (PCB) resonator structures.

We present the design and performance of a broad-band single-chip integrated transceiver specifically conceived for nuclear magnetic resonance magnetometry. The single-chip transceiver is realized using a standard silicon complementary metal-oxide-semiconductor integrated circuit technology. A radio-frequency (RF) transmit amplifier, a transmit/receive switch, a low noise RF receive amplifier, a quadrature (IQ)-mixer, and two intermediate frequency amplifiers are integrated on a single silicon chip of 1.8 mm 2 . The advantages and problematic aspects with respect to conventional discrete electronic approaches are discussed. We show the results of magnetic field measurements performed at 1.4 and 7.05 T, using solid and liquid samples having volumes from 40 μl down to 100 pl. Particular attention is devoted to the comparison of the experimentally measured magnetic field standard deviation with respect to the Cramer-Rao lower bound value. With a sample of distilled water (T 1 ≅ T 2 ≅ 3 s, T 2 * ≅ 20 ms) having a volume of 40 μl, a standard deviation of 2.5 nT at 7.05 T (i.e., 0.5 ppb) in 1 s of averaging time is achieved, with a projected Cramer-Rao lower bond of 8 pT (i.e., 1.1 ppt).

Single-chip microwave oscillators are promising devices for inductive electron spin resonance spectroscopy (ESR) experiments on nanoliter and subnanoliter samples. Two major problems of the previously reported designs were the large minimum microwave magnetic field (0.1-0.7 mT) and large power consumption (0.5-200 mW), severely limiting their use for the investigation of samples having long relaxation times and for operation at low temperatures. Here we report on the design and characterization of a single-chip ESR detector operating with a microwave magnetic field and a power consumption orders of magnitude lower compared with previous designs. These significant improvements are mainly due to the use of a high electron mobility transistor (HEMT) technology instead of a complementary metal-oxide semiconductor (CMOS) technology. The realized single-chip ESR detector, which operates at 11.2 GHz, consists of an LC Colpitts oscillator realized with a single high-electron mobility transistor and a co-integrated single turn planar coil having a diameter of 440 μm. The realized detector operates from 300 K down to 1.4 K, at least. Its minimum microwave magnetic field is 0.4 μT at 300 K and 0.06 μT at 1.4 K, whereas its power consumption is 90 μW at 300 K and 4 μW at 1.4 K, respectively. The experimental spin sensitivity on a sensitive volume of about 30 nL, as measured with a single crystal of α,γ-bisdiphenylene-β-phenylallyl (BDPA)/benzene complex, is of 8 × 10 10  spins/Hz 1/2 at 300 K and 2 × 10 9  spins/Hz 1/2 at 10 K, respectively. In a volume of about 100 pL, located in proximity to the coil wire, the spin sensitivity improves by two orders of magnitude., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We previously demonstrated that socially isolated rats at weaning showed a significant decrease in corticosterone and adrenocorticotropic hormone (ACTH) levels, associated with an enhanced response to acute stressful stimuli. Here we shown that social isolation decreased levels of total corticosterone and of its carrier corticosteroid-binding globulin, but did not influence the availability of the free active fraction of corticosterone, both under basal conditions and after acute stress exposure. Under basal conditions, social isolation increased the abundance of glucocorticoid receptors, while it decreased that of mineralocorticoid receptors. After acute stress exposure, socially isolated rats showed long-lasting corticosterone, ACTH and corticotrophin releasing hormone responses. Moreover, while in the hippocampus and hypothalamus of group-housed rats glucocorticoid receptors expression increased with time and reached a peak when corticosterone levels returned to basal values, in socially isolated rats expression of glucocorticoid receptors did not change. Finally, social isolation also affected the hypothalamic endocannabinoid system: compared to group-housed rats, basal levels of anandamide and cannabinoid receptor type 1 were increased, while basal levels of 2-arachidonoylglycerol were decreased in socially isolated rats and did not change after acute stress exposure. The present results show that social isolation in male rats alters basal HPA axis activity and impairs glucocorticoid-mediated negative feedback after acute stress. Given that social isolation is considered an animal model of several neuropsychiatric disorders, such as generalized anxiety disorder, depression, post-traumatic stress disorder and schizophrenia, these data could contribute to better understand the alterations in HPA axis activity observed in these disorders., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Variations in maternal care in the rat influence the development of individual differences in behavioral and endocrine responses to stress. This study aimed to examine the interaction between intragastric intubation during late gestation and postpartum stress, induced by pup separation, on maternal behavior and on dams' emotional state and HPA axis function. Rats received intragastric intubation of water on days 12-20 of gestation or remained untreated in their home cage (naïve dams). Pup separation was used as a model of postpartum stress. The procedure consisted of a daily separation of the dam from its litter for 3h from PND 3 until PND 15. Pup separation was carried out in both naïve and intubated dams. The behavioral results indicate that the association of these two stressors significantly decreased arched-back nursing (ABN) and licking and grooming (LG), behaviors considered important parameters to discriminate the high quality of maternal care. Moreover, dams that received both stressors displayed less nest building and blanket nursing behaviors; no effect on the frequency of passive and total nursing was recorded. The analysis of single effects on ABN and LG, revealed that dams that underwent gestational stress induced by intragastric intubation displayed less LG, but ABN was overall unchanged. On the contrary, pup separation stress significantly increased ABN and LG upon reunion of naïve dams with their pups. Treatments per se or the association of both induced modest changes in plasma levels of allopregnanolone and corticosterone that likely did not influence maternal care. These data show that the association of a mild stress during gestation with an unfavorable experience after parturition had a significant impact on maternal care. This effect seems independent from HPA axis activation or from changes in emotional state; further studies would be necessary to ascertain the neural changes that could contribute to altered maternal behavior in stressed mothers. Moreover, these results suggest that the use of intragastric intubation during gestation would interfere with measures of drug-induced changes in maternal behavior and likely their consequences on the offspring., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Rationale: Social isolation of rats immediately after weaning is thought to represent an animal model of anxiety-like disorders. Socially isolated virgin females showed a significant decrease in allopregnanolone levels, associated with increased anxiety-related behavior compared with group-housed rats., Objectives: The present study investigates whether post-weaning social isolation affects maternal behavior and assesses neuroactive steroid levels in adult female rats during pregnancy and postpartum., Results: Socially isolated dams displayed a reduction in the frequency of arched back nursing (ABN) behavior compared to group-housed dams. In addition, both total and active nursing were lower in socially isolated dams compared to group-housed dams. Compared to virgin females, pregnancy increases allopregnanolone levels in group-housed as well as isolated dams and such increase was greater in the latter group. Compared to pregnancy levels, allopregnanolone levels decreased after delivery and this decrease was more pronounced in isolated than group-housed dams. Moreover, the fluctuations in plasma corticosterone levels that occur in late pregnancy and during lactation follow a different pattern in socially isolated vs. group-housed rats., Conclusions: The present results show that social isolation in female rats decreases maternal behavior; this effect is associated with lower allopregnanolone concentrations at postpartum, which may account, at least in part, for the poor maternal care observed in socially isolated dams. In support of this conclusion is the finding that finasteride-treated dams, which display a decrease in plasma allopregnanolone levels, also showed a marked reduction in maternal care, suggesting that allopregnanolone may contribute to the quality of maternal care.

Hyperpolarization via dynamic nuclear polarization (DNP) is pivotal for boosting magnetic resonance imaging (MRI) sensitivity and dissolution DNP can be used to perform in vivo real-time 13 C MRI. The type of applications is however limited by the relatively fast decay time of the hyperpolarized spin state together with the constraint of having to polarize the 13 C spins in a dedicated apparatus nearby but separated from the MRI magnet. We herein demonstrate that by polarizing 13 C with photo-induced radicals, which can be subsequently annihilated using a thermalization process that maintains the sample temperature below its melting point, hyperpolarized 13 C-substrates can be extracted from the DNP apparatus in the solid form, while maintaining the enhanced 13 C polarization. The melting procedure necessary to transform the frozen solid into an injectable solution containing the hyperpolarized 13 C-substrates can therefore be performed ex situ, up to several hours after extraction and storage of the polarized solid.

We report on the design and characterization of single-chip electron spin resonance (ESR) detectors operating at 50GHz, 92GHz, and 146GHz. The core of the single-chip ESR detectors is an integrated LC-oscillator, formed by a single turn aluminum planar coil, a metal-oxide-metal capacitor, and two metal-oxide semiconductor field effect transistors used as negative resistance network. On the same chip, a second, nominally identical, LC-oscillator together with a mixer and an output buffer are also integrated. Thanks to the slightly asymmetric capacitance of the mixer inputs, a signal at a few hundreds of MHz is obtained at the output of the mixer. The mixer is used for frequency down-conversion, with the aim to obtain an output signal at a frequency easily manageable off-chip. The coil diameters are 120μm, 70μm, and 45μm for the U-band, W-band, and the D-band oscillators, respectively. The experimental frequency noises at 100kHz offset from the carrier are 90Hz/Hz 1/2 , 300Hz/Hz 1/2 , and 700Hz/Hz 1/2 at 300K, respectively. The ESR spectra are obtained by measuring the frequency variations of the single-chip oscillators as a function of the applied magnetic field. The experimental spin sensitivities, as measured with a sample of α,γ-bisdiphenylene-β-phenylallyl (BDPA)/benzene complex, are 1×10 8 spins/Hz 1/2 , 4×10 7 spins/Hz 1/2 , 2×10 7 spins/Hz 1/2 at 300K, respectively. We also show the possibility to perform experiments up to 360GHz by means of the higher harmonics in the microwave field produced by the integrated single-chip LC-oscillators., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Nuclear magnetic resonance (NMR) spectroscopy enables non-invasive chemical studies of intact living matter. However, the use of NMR at the volume scale typical of microorganisms is hindered by sensitivity limitations, and experiments on single intact organisms have so far been limited to entities having volumes larger than 5 nL. Here we show NMR spectroscopy experiments conducted on single intact ova of 0.1 and 0.5 nL (i.e. 10 to 50 times smaller than previously achieved), thereby reaching the relevant volume scale where life development begins for a broad variety of organisms, humans included. Performing experiments with inductive ultra-compact (1 mm 2 ) single-chip NMR probes, consisting of a low noise transceiver and a multilayer 150 μm planar microcoil, we demonstrate that the achieved limit of detection (about 5 pmol of 1 H nuclei) is sufficient to detect endogenous compounds. Our findings suggest that single-chip probes are promising candidates to enable NMR-based study and selection of microscopic entities at biologically relevant volume scales.

A high sensitivity field asymmetric ion mobility spectrometer (FAIMS) was designed, fabricated, and tested. The main components of the system are a 10.6 eV UV photoionization source, an ion filter driven by a high voltage/high frequency n-MOS inverter circuit, and a low noise ion detector. The ion filter electronics are capable to generate square waveforms with peak-to-peak voltages up to 1000 V at frequencies up to 1 MHz with adjustable duty cycles. The ion detector current amplifier has a gain up to 10 12 V/A with an effective equivalent input noise level down to about 1 fA/Hz 1/2 during operation with the ion filter at the maximum voltage and frequency. The FAIMS system was characterized by detecting different standard chemical compounds. Additionally, we investigated the use of a synchronous modulation/demodulation technique to improve the signal-to-noise ratio in FAIMS measurements. In particular, we implemented the modulation of the compensation voltage with the synchronous demodulation of the ion current. The analysis of the measurements at low concentration levels led to an extrapolated limit of detection for acetone of 10 ppt with an averaging time of 1 s.

In this paper, we present a fully-integrated receiver for NMR microscopy applications manufactured in a 0.13μm CMOS technology. The design co-integrates a 10-turn planar detection coil together with a complete quadrature, low-IF downconversion receiver on a single chip, which operates from a single 1.5V supply with a total power dissipation of 18mW. The detector's measured time-domain spin sensitivity is 3×10(13)(1)Hspins/Hz at 7T. Additionally, the paper discusses two important aspects of NMR microscopy using planar detection coils: the link between the detection coil's spin sensitivity and the achievable image SNR and the correction of image artifacts induced by the inhomogeneous sensitivity profile of planar detection coils. More specifically, we derive analytical expressions for both the theoretical image SNR as a function of the coil's spin sensitivity and the sensitivity correction for a known coil sensitivity profile in CTI MR imaging experiments. Both expressions are validated using measured data in the imaging section of the paper. Thanks to the improved spin sensitivity of the utilized integrated receiver chip compared to a previously presented design, we were able to obtain sensitivity corrected images in a 7T spectroscopy magnet with isotropic resolutions of 9.6μm and 5μm with single-shot SNRs of 37 and 15 in relatively short imaging times of 4.4h and 24h, respectively., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Peri-ictal water drinking (PIWD) has been reported as the action of drinking during or within two minutes of an electroclinical seizure. It is considered a peri-ictal vegetative symptom, evident both during childhood and adulthood epilepsy. The aim of this paper was to describe the clinical and electroencephalographic features of two new adult subjects suffering from symptomatic temporal lobe epilepsy with episodes of PIWD recorded by VIDEO-EEG and to review literature data in order to better define this peculiar event during seizures, a rare and probably underestimated semiological sign. To date, 51 cases with focal epilepsy and seizures associated with PIWD have been reported. All patients presented with temporal lobe epilepsy. All cases but one had symptomatic epilepsy. Most of the patients had an involvement of the right hemisphere. Water drinking was reported as an ictal sign in the majority of patients, and less frequently was reported as postictal. We believe that PIWD might be considered a rare automatic behaviour, like other automatisms. Automatisms are more frequently described in patients with temporal lobe epilepsy. PIWD was reported also to have lateralizing significance in the non-dominant temporal lobe, however, because of its rarity, this finding remains unclear.

Objective: To identify novel genes implicated in epilepsy with auditory features (EAF) in phenotypically heterogeneous families with unknown molecular basis., Methods: We identified 15 probands with EAF in whom an LGI1 mutation had been excluded. We performed electroclinical phenotyping on all probands and available affected relatives. We used whole-exome sequencing (WES) in 20 individuals with EAF (including all the probands and 5 relatives) to identify single nucleotide variants, small insertions/deletions, and copy number variants., Results: WES revealed likely pathogenic variants in genes that had not been previously associated with EAF: a CNTNAP2 intragenic deletion, 2 truncating mutations of DEPDC5, and a missense SCN1A change., Conclusions: EAF is a clinically and molecularly heterogeneous disease. The association of EAF with CNTNAP2, DEPDC5, and SCN1A mutations widens the phenotypic spectrum related to these genes. CNTNAP2 encodes CASPR2, a member of the voltage-gated potassium channel complex in which LGI1 plays a role. The finding of a CNTNAP2 deletion emphasizes the importance of this complex in EAF and shows biological convergence.

In this article, we present an integrated broadband complementary metal-oxide semiconductor single-chip transceiver suitable for the realization of multi-nuclear pulsed nuclear magnetic resonance (NMR) probes. The realized single-chip transceiver can be interfaced with on-chip integrated microcoils or external LC resonators operating in the range from 1 MHz to 1 GHz. The dimension of the chip is about 1 mm(2). It consists of a radio-frequency (RF) power amplifier, a low-noise RF preamplifier, a frequency mixer, an audio-frequency amplifier, and fully integrated transmit-receive switches. As specific example, we show its use for multi-nuclear NMR spectroscopy. With an integrated coil of about 150 μm external diameter, a (1)H spin sensitivity of about 1.5 × 10(13) spins/Hz(1/2) is achieved at 7 T.

To evaluate if pregnancy induces a change in seizure frequency and in percentage of subjects remaining seizure-free. This is a prospective case-control study conducted in our tertiary epilepsy centre. Controls were matched 2:1 with the cases for relevant clinical parameters. Cases had to be referred to our centre for at least 9 months before-pregnancy, during pregnancy and the-9-months-after-birth. Controls were followed for the correspondent periods of time: named respectively control period 1-2-3. Seizure frequency was defined as "improved" if there was a 50 % of reduction, "worsened" if there was a 50 % of increase, and "unchanged" in the rest of cases. We recruited 36 cases and 72 controls [in both group mean age was 28 years, partial epilepsy (80.6 %), generalized epilepsy (19.4 %)]; 30 cases and 60 controls were seizure-free before pregnancy and in period 1, respectively. During pregnancy 72 % of cases remained "unchanged" while 8 and 19 % respectively "improved" and "worsened"; moreover, there was no statistical difference in the number of seizure-free patients and in the monthly seizure frequencies. No differences were found in controls. In this prospective case-control study, pregnancy does not affect seizure frequency in women with epilepsy.

We report on the design and characterization of a single-chip electron spin resonance detector, operating at a frequency of about 20 GHz and in a temperature range extending at least from 300 K down to 4 K. The detector consists of an LC oscillator formed by a 200 μm diameter single turn aluminum planar coil, a metal-oxide-metal capacitor, and two metal-oxide-semiconductor field effect transistors used as negative resistance network. At 300 K, the oscillator has a frequency noise of 20 Hz/Hz(1/2) at 100 kHz offset from the 20 GHz carrier. At 4 K, the frequency noise is about 1 Hz/Hz(1/2) at 10 kHz offset. The spin sensitivity measured with a sample of DPPH is 10(8)spins/Hz(1/2) at 300 K and down to 10(6)spins/Hz(1/2) at 4 K., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We report the fabrication, functionalization and testing of microdevices for cell culture and cell traction force measurements in three-dimensions (3D). The devices are composed of bent cantilevers patterned with cell-adhesive spots not lying on the same plane, and thus suspending cells in 3D. The cantilevers are soft enough to undergo micrometric deflections when cells pull on them, allowing cell forces to be measured by means of optical microscopy. Since individual cantilevers are mechanically independent of each other, cell traction forces are determined directly from cantilever deflections. This proves the potential of these new devices as a tool for the quantification of cell mechanics in a system with well-defined 3D geometry and mechanical properties.

We report on the design, fabrication, and characterization of an integrated detector for electron spin resonance spectroscopy operating at 27 GHz. The microsystem, consisting of an LC-oscillator and a frequency division module, is integrated onto a single silicon chip using a conventional complementary metal-oxide-semiconductor technology. The achieved room temperature spin sensitivity is about 10(8)spins/G Hz(1/2), with a sensitive volume of about (100 μm)(3). Operation at 77K is also demonstrated., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We present a fully integrated detector suitable for active tracking of interventional devices in MR-guided interventions. The single-chip microsystem consists of a detection coil, a tuning capacitor, an intermediate frequency downconversion receiver, and a phase-locked-loop-based frequency synthesizer. Thanks to the integrated mixer, the chip output stage delivers an analog frequency-downconverted NMR signal in the frequency range from 0 to 200 kHz. The microchip, realized in a standard complementary metal oxide semiconductor technology, has a size of 1 × 2 × 0.74 mm(3) and operates at a frequency of 63 MHz (i.e., in 1.5 T clinical scanners). Tests in a standard clinical scanner demonstrate the compatibility of the complementary metal oxide semiconductor microchip with clinical MRI systems. Using a solid sample of cis-polyisoprene having a size of 1 × 1.9 × 0.8 mm(3) as internal signal source, the detector achieves a three-dimensional isotropic spatial resolution of 0.15 mm in a measuring time of 100 ms., (Copyright © 2011 Wiley-Liss, Inc.)

We present a fully integrated CMOS receiver for micro-magnetic resonance imaging together with a custom-made micro-gradient system. The receiver is designed for an operating frequency of 300 MHz. The chip consists of an on-chip detection coil and tuning capacitor as well as a low-noise amplifier and a quadrature downconversion mixer with corresponding low-frequency amplification stages. The design is realized in a 0.13 μm CMOS technology, it occupies a chip area of 950 × 800 μm² and it draws 50 mA from a supply voltage of 1.8 V. The achieved time-domain spin sensitivity is 5×10(14)spins/Hz. Images of phantoms obtained in our custom-made gradient system with 8 μm isotropic resolution are reported., (Copyright © 2010 Elsevier Inc. All rights reserved.)

We investigated the performance of Hall sensors with different Co-C ratios, deposited directly in nanostructured form, using Co(2)(CO)(8) gas molecules, by focused-electron or ion-beam-induced deposition. Due to the enhanced intergrain scattering in these granular wires, the extraordinary Hall effect can be increased by two orders of magnitude with respect to pure Co, up to a magnetic field sensitivity of 1 Omega T(-1). We show that the best magnetic field resolution at room temperature is obtained for Co ratios between 60% and 70% and is better than 1 microT Hz(-1/2). For an active area of the sensor of 200 x 200 nm(2), the room temperature magnetic flux resolution is phi(min) = 2 x 10(-5)phi(0) in the thermal noise frequency range, i.e. above 100 kHz.

Purpose: To count patients with newly diagnosed epilepsy entering early and late remission and to identify prognostic predictors of late remission., Methods: Children and adults with previously untreated epilepsy from two Italian tertiary centers (Monza, Bari) were the study population. All patients received monotherapy at treatment start; drug choice and schedule were left to the physician's judgment. A retrospective audit was performed and the following prognostic predictors were identified: age, gender, putative etiology, first electroencephalography (EEG) record, neurologic and psychiatric examination, disease duration at diagnosis, seizure type(s) and number prior to starting treatment, epilepsy syndrome, and first antiepileptic drug. Early remission was defined by 2-year seizure control immediately after treatment start. Late remission was defined by 2-year seizure control achieved at least 24 months after treatment start. Prognostic predictors were assessed by logistic regression analysis, adjusting for age, gender, and center., Results: One hundred seventy-four women and 178 men (mean age 31.5 years) were included and followed for 2399.6 person-years. The cumulative time-dependent probability of 2-year remission was 56.3% at 2 years after treatment start, and 62.6, 69.4, and 79.5% at 3, 5, and 10 years. One hundred fifteen patients (23.0%) achieved early remission and 38 patients (10.8%) achieved late remission. The interaction between partial seizures and number of seizures prior to treatment was the only independent predictor of late remission., Discussion: The course of epilepsy and the chance of remission are together a complex and dynamic process, possibly explained by the diversity of the mechanisms underlying drug response and the use of an increasing number of drugs.

We describe a setup for the x-ray detection of ferromagnetic resonance in the longitudinal geometry using element-specific transmission measurements. Thin magnetic film samples are placed in a static magnetic field collinear with the propagation direction of a polarized soft x-ray beam and driven to ferromagnetic resonance by a continuous wave microwave magnetic field perpendicular to it. The transmitted photon flux is measured both as a function of the x-ray photon energy and as a function of the applied static magnetic field. We report experiments performed on a 15 nm film of doped Permalloy (Ni(73)Fe(18)Gd(7)Co(2)) at the L(3)/L(2)-edges of Fe, Co, and Ni. The achieved ferromagnetic resonance sensitivity is about 0.1 monolayers/square root(Hz). The obtained results are interpreted in the framework of a conductivity tensor based formalism. The factors limiting the sensitivity as well as different approaches for the x-ray detection of ferromagnetic resonance are discussed.

We present the first single-chip array of integrated NMR receivers for parallel spectroscopy and imaging. The array, optimized for operation at 300 MHz, is composed of eight separate channels, with each channel consisting of a detection coil, a tuning capacitor, a low noise amplifier and a 50 ohm buffer. As all the integrated electronics are placed underneath the reception coils, the array is densely packed. Each single-channel reception coil has a diameter of 500 microm, resulting in a total active area of 1 mm by 2 mm for the array. The (1)H time-domain spin sensitivity of a single channel is approximately 1x10(15) spins/square root(Hz).

We have realized an innovative integrated detector for electron spin resonance spectroscopy. The microsystem, consisting of an LC oscillator, a mixer, and a frequency division module, is integrated onto a single silicon chip using a conventional complementary metal-oxide-semiconductor technology. The implemented detection method is based on the measurement of the variation of the frequency of the integrated LC oscillator as a function of the applied static magnetic field, caused by the presence of a resonating sample placed over the inductor of the LC-tank circuit. The achieved room temperature spin sensitivity is about 10(10) spinsGHz(12) with a sensitive volume of about (100 microm)(3).