Comparison of electrical and optical transduction modes of DNA-wrapped SWCNT nanosensors for the reversible detection of neurotransmitters.

In this study, we compare the electrical and optical signal transduction of nanoscale biosensors based on single-walled carbon nanotubes (SWCNTs). Solution processable single-stranded (ss) DNA-wrapped SWCNTs were used for the fabrication of the distinct sensors. For electrical measurements, SWCNTs were assembled from solution onto pre-patterned electrodes by electric-field-assisted assembly in field-effect transistor (FET) configuration. A combination of micro- and nano-fabrication and microfluidics enabled the integration into a sensing platform that allowed real-time and reversible detection. For optical measurements, the near-infrared (NIR) fluorescence of the SWCNTs was acquired directly from solution. The detection of important biomolecules was investigated in high-ionic strength solution (0.5xPBS). Increase in fluorescence intensities correlated with a decrease in the SWCNTs electrical current and enabled detection of the important biomolecules dopamine, epinephrine, and ascorbic acid. For riboflavin, however, a decrease in the fluorescence intensity could not be associated with changes in the SWCNTs electrical current, which indicates a different sensing mechanism. The combination of SWCNT-based electrical and optical transduction holds great potential for selective detection of biomarkers in next generation portable diagnostic assays.

Perampanel during pregnancy: Description of four cases.

Perampanel (PER) is approved in Italy as an adjunctive treatment for focal-onset seizures (FOS) and generalized tonic-clonic seizures (GTCs), and it could be an alternative to valproate in young women diagnosed with idiopathic generalized epilepsy. Nevertheless, clinical data about the outcome of pregnancies in women exposed to PER are lacking. Here, we report retrospectively collected data from four women suffering from FOS who were exposed to PER during pregnancy. Three pregnancies were carried out with PER as add-on therapy during the entire gestation (8 mg/day in two patients and 6 mg/day in one), without seizure frequency variations. The fourth patient started PER 2 mg/day as monotherapy during the 13th week of pregnancy due to seizure relapse and continued it until delivery with complete seizure control. All pregnancies showed good outcomes, and their newborns did not possess major congenital malformations. Apgar scores and auxological parameters at birth were normal. Fetal pathology in follow-up during pregnancies was absent in all cases. In our patients PER was well tolerated and appeared safe for the fetuses and did not result in major malformations or adverse events at birth. Nevertheless, this is a report involving a small number of patients and it does not suggest the general use of PER is safe during pregnancy.

Eyelid myoclonia with absences, intellectual disability and attention deficit hyperactivity disorder: a clinical phenotype of the RORB gene mutation.

Eyelid myoclonia with absences is recently included in the category of childhood epileptic syndromes. It is clinically characterized by brief seizures of eyelid myoclonia, sometimes followed by absences, and it is associated to EEG generalized discharges of polyspikes or polyspike-waves, which are triggered by eyes closure in a well-lit room. This epileptic syndrome probably has a genetic origin, as well as other genetic generalized epilepsies, in particular photosensitive epilepsies. We describe the case of a patient affected by eyelid myoclonia with absences, intellectual disability, and attention deficit hyperactivity disorder (ADHD), with a de novo mutation of the RORB gene (retinoid-related orphan receptor ß); this gene is involved in vivo in different neuronal processes among which are migration and differentiation. We suggest that its mutation in our patient can be considered the cause of the aberrant functioning of the cerebral cortex, which is clinically expressed by epilepsy and neurodevelopment disorders.

3D printed microchannels for sub-nL NMR spectroscopy.

Nuclear magnetic resonance (NMR) experiments on subnanoliter (sub-nL) volumes are hindered by the limited sensitivity of the detector and the difficulties in positioning and holding such small samples in proximity of the detector. In this work, we report on NMR experiments on liquid and biological entities immersed in liquids having volumes down to 100 pL. These measurements are enabled by the fabrication of high spatial resolution 3D printed microfluidic structures, specifically conceived to guide and confine sub-nL samples in the sub-nL most sensitive volume of a single-chip integrated NMR probe. The microfluidic structures are fabricated using a two-photon polymerization 3D printing technique having a resolution better than 1 µm3. The high spatial resolution 3D printing approach adopted here allows to rapidly fabricate complex microfluidic structures tailored to position, hold, and feed biological samples, with a design that maximizes the NMR signals amplitude and minimizes the static magnetic field inhomogeneities. The layer separating the sample from the microcoil, crucial to exploit the volume of maximum sensitivity of the detector, has a thickness of 10 µm. To demonstrate the potential of this approach, we report NMR experiments on sub-nL intact biological entities in liquid media, specifically ova of the tardigrade Richtersius coronifer and sections of Caenorhabditis elegans nematodes. We show a sensitivity of 2.5x1013 spins/Hz1/2 on 1H nuclei at 7 T, sufficient to detect 6 pmol of 1H nuclei of endogenous compounds in active volumes down to 100 pL and in a measurement time of 3 hours. Spectral resolutions of 0.01 ppm in liquid samples and of 0.1 ppm in the investigated biological entities are also demonstrated. The obtained results may indicate a route for NMR studies at the single unit level of important biological entities having sub-nL volumes, such as living microscopic organisms and eggs of several mammalians, humans included.

Low doses of prenatal ethanol exposure and maternal separation alter HPA axis function and ethanol consumption in adult male rats.

Adverse maternal behaviors during pregnancy and unfavorable postnatal experiences during development are associated with an increased risk of developing psychiatric disorders, as well as, a vulnerability to alcohol addiction in adulthood. Here, we examined the effects of combined ethanol exposure during late pregnancy and postnatal maternal separation (MS) on HPA responsiveness, anxiety behavior and preference for alcohol consumption in adult male rats. Animals exposed to both conditions revealed a decrease in blood levels of allopregnanolone accompanied by increased anxiety behavior. In addition, basal blood levels of corticosterone were markedly decreased in all experimental groups while increases in the foot-shock-induced corticosterone levels were more pronounced in MS animals. Finally, evaluating EtOH drinking behavior, MS animals exhibited a remarkable EtOH preference even at low doses (0.1-1%). Altogether, these data suggest that adverse conditions, alone or in combination, may alter anxiety-like states as well as modify behavior towards alcohol consumption.

Sex differences in the outcome of juvenile social isolation on HPA axis function in rats.

Women are more likely than men to suffer from anxiety disorders and major depression. These disorders share hyperresponsiveness to stress as an etiological factor. Thus, sex differences in brain arousal systems and their regulation by chronic stress may account for the increased vulnerability to these disorders in women. Social isolation is a model of early life stress that results in neurobiological alterations leading to increased anxiety-like and depressive-like behaviors. Here we investigated the sex difference in the effects of post-weaning social isolation on acute stress sensitivity and behavior in rats. In both sexes, social isolation at weaning reduced basal levels of the neuroactive steroid allopregnanolone in the brain and of corticosterone in plasma. Moreover, acute stress increased plasma corticosterone levels in both group-housed and socially isolated male and female rats; however this effect was greater in male than female rats subjected to social isolation. Intriguingly, group-housed female rats showed no change in plasma and brain levels of allopregnanolone after acute foot-shock stress. The absence of stress-induced effects on allopregnanolone synthesis might be due to the physiologically higher levels of this hormone in females vs. males. Accordingly, increasing allopregnanolone levels in male rats blunted the response to foot-shock stress in these animals. Socially isolated male, but not female, rats also display depressive-like behavior and increased hippocampal brain-derived neurotrophic factor (BDNF). The ovarian steroids could "buffer" the effect of this adverse experience in females on these parameters. Finally, the dexamethasone (DEX) suppression test indicated that the chronic stress associated with social isolation impairs feedback inhibition in both sexes in which an increase in the abundance of glucocorticoid receptors (GRs) in the hippocampus was found. Altogether, these results demonstrate that social isolation affects neuroendocrine reactivity to stress, plasticity and emotionality in a sexually dimorphic manner.

Maternal separation attenuates the effect of adolescent social isolation on HPA axis responsiveness in adult rats.

Adverse early life experiences that occur during childhood and adolescence can have negative impacts on behavior later in life. The main goal of our work was to assess how the association between stressful experiences during neonatal and adolescent periods may influence stress responsiveness and brain plasticity in adult rats. Stressful experiences included maternal separation and social isolation at weaning. Three hours of separation from the pups (3-14 PND) significantly increased frequencies of maternal arched-back nursing and licking-grooming across the first two weeks postpartum. Separation also induced a long-lasting increase in dams blood levels of corticosterone. Maternal separation did not modify brain and plasma allopregnanolone and corticosterone levels in adult offspring, but they demonstrate partial recovery from the reduction induced by social isolation during adolescence. Moreover, the enhancement of corticosterone and allopregnanolone levels induced by foot shock stress in socially isolated animals that were subjected to maternal separation was markedly reduced with respect to that observed in animals that were just socially isolated. All experimental groups showed a significant reduction of BDNF and Arc protein expression in the hippocampus. However, the reduction of BDNF observed in animals that were maternally separated and subjected to social isolation was less significantly pronounced than in animals that were just socially isolated. The results sustained the mismatch hypothesis stating that aversive experiences early in life trigger adaptive processes, thereby rendering an individual to be better adapted to aversive challenges later in life.

Room temperature strong coupling between a microwave oscillator and an ensemble of electron spins.

We demonstrate theoretically and experimentally the possibility to achieve the strong coupling regime at room temperature with a microwave electronic oscillator coupled with an ensemble of electron spins. The coupled system shows bistable behaviour, with a broad hysteresis and sharp transitions. The coupling strength and the hysteresis width can be adjusted through the number of spins in the ensemble, the temperature, and the microwave field strength.

Longitudinal detection of ferromagnetic resonance using x-ray transmission measurements.

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.

Single-chip detector for electron spin resonance spectroscopy.

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).

Planar microcoil-based microfluidic NMR probes.

Microfabricated small-volume NMR probes consisting of electroplated planar microcoils integrated on a glass substrate with etched microfluidic channels are fabricated and tested. 1H NMR spectra are acquired at 300 MHz with three different probes having observed sample volumes of respectively 30, 120, and 470 nL. The achieved sensitivity enables acquisition of an 1H spectrum of 160 microg sucrose in D2O, corresponding to a proof-of-concept for on-chip NMR spectroscopy. Increase of mass-sensitivity with coil diameter reduction is demonstrated experimentally for planar microcoils. Models that enable quantitative prediction of the signal-to-noise ratio and of the influence of microfluidic channel geometry on spectral resolution are presented and successfully compared to the experimental data. The main factor presently limiting sensitivity for high-resolution applications is identified as being probe-induced static magnetic field distortions. Finally, based on the presented model and measured data, future performance of planar microcoil-based microfluidic NMR probes is extrapolated and discussed.

Bilateral extensive skin necrosis of the lower limbs following prolonged epidural blockade.

Skin necrosis has not been described as a complication following epidural sympathetic blockade. We report a case of bilateral extensive skin necrosis of the lower limbs after a 48-hour lumbar epidural blockade in a 71-year-old patient with right hemiplegia and mitral valve regurgitation, without any preoperative clinical evidence of peripheral vascular disease or diabetes, who underwent transurethral prostatectomy.

[Synovectomy]. / La sinoviectomia.

The synovial membrane--the articular district of the s.i.--responds to pathogenic stimuli by cell hyperplasia, giving rise to the so-called pannus. This together with regression and haemorrhage, may lead to self-maintenance of the condition, over and above the persistence of the original insult, resulting in chronicity and degeneration. If performed when the disease is still limited to histiocyte hyperplasia, synovectomy is effective in both single-joint forms and systemic conditions, such as rheumatoid arthritis. These conclusions (already evident in the literature) emerged from a review of a series of 67 synovectomies and 29 tenosynovectomies performed between 1969 and 1978 for various joint and tendon afflictions (not including T.B.) marked by synovial hyperplasia.

[A case of sacral neurinoma]. / Un caso di neurinoma del sacro.

A case of sacral neurinoma diagnosed in a 67-year-old woman whose clinical symptomatology consisted for fully 54 years of faint but persistent episodes of lumbo- and sacralgia is reported. Only at the terminal moment of observation did the patient present motor and sensitivity disturbances in the lower extremities, paralysis of the sphincters and sacral decubitus. The mass was identified radiologically and submitted to biopsy. It was localized in the left wing of the sacrum and on the corresponding side of the iliac bone, and presented a diameter of 6 X 9 cm. The slow, practically asymptomatic course, the exclusively intra-osseous site, the histological report and late onset of a cauda syndrome, suggest that the origin of the neoplasia lies in the sacral nerves.

[Acrylic cement in the osteosynthesis of pathological fractures]. / Il cemento acrilico nell'osteosintesi delle fratture patologiche

After outlining the problem of pathological fractures in patients suffering from malignant tumours, a recent acrylic cement osteosynthesis technique is presented. This makes immediate immobilization of the fracture possible, alleviation of pain and so early use of the fractured extremity. The personal series is illustrated and it is concluded that the technique also offers suitable prophylaxis when radiography of the skeleton points to osteolytic areas in which pathological fracture can be foreseen.

[Pseudotumoral progression in a case of periosteal ossification of the femur]. / Su di un caso di ossificazione periostale del femore a sviluppo pseudotumorale

A case of periosteal ossification of the femur in a 14-yr-old boy is reported. The clinical, radiological and scintiscan pictures illustrated marked pseudotumoral lesions in a subject with a mild form of osteopsathyrosis.