Non-adiabatic direct quantum dynamics using force fields: Toward solvation.

Quantum dynamics simulations are becoming a powerful tool for understanding photo-excited molecules. Their poor scaling, however, means that it is hard to study molecules with more than a few atoms accurately, and a major challenge at the moment is the inclusion of the molecular environment. Here, we present a proof of principle for a way to break the two bottlenecks preventing large but accurate simulations. First, the problem of providing the potential energy surfaces for a general system is addressed by parameterizing a standard force field to reproduce the potential surfaces of the molecule's excited-states, including the all-important vibronic coupling. While not shown here, this would trivially enable the use of an explicit solvent. Second, to help the scaling of the nuclear dynamics propagation, a hierarchy of approximations is introduced to the variational multi-configurational Gaussian method that retains the variational quantum wavepacket description of the key quantum degrees of freedom and uses classical trajectories for the remaining in a quantum mechanics/molecular mechanics like approach. The method is referred to as force field quantum dynamics (FF-QD), and a two-state ππ*/nπ* model of uracil, excited to its lowest bright ππ* state, is used as a test case.

Modifications of lung microbiota structure in traumatic brain injury ventilated patients according to time and enteral feeding formulas: a prospective randomized study.

BACKGROUND: Specialized diets enriched with immune nutrients could be an important supplement in patients (pts) with acute traumatic brain injury (TBI). Omega-3 and arginine may interact with immune response and microbiota. No data are available about the role of the specialized diets in modulating the lung microbiota, and little is known about the influence of lung microbiota structure in development of ventilator-associated pneumonia (VAP) in TBI pts. The aims of this study are to evaluate the impact of specific nutrients on the lung microbiota and the variation of lung microbiota in TBI pts developing VAP. METHODS: A cohort of 31 TBI pts requiring mechanical ventilation in ICU was randomized for treatment with specialized (16pts) or standard nutrition (15pts). Alpha and beta diversity of lung microbiota were analyzed from bronco Alveolar Lavage (BAL) samples collected at admission and 7 days post-ICU admission in both groups. A further analysis was carried out on the same samples retrospectively grouped in VAP or no VAP pts. RESULTS: None developed VAP in the first week. Thereafter, ten out of thirty-one pts developed VAP. The BAL microbiota on VAP group showed significant differences in beta diversity and Staphylococcus and Acinetobacter Genera were high. The specialized nutrition had influence on beta diversity that reached statistical significance only in Bray-Curtis distance. CONCLUSION: Our data suggest that TBI patients who developed VAP during ICU stay have different structures of BAL microbiota either at admission and at 7 days post-ICU admission, while no correlation has been observed between different enteral formulas and microbiota composition in terms of richness and evenness. These findings suggest that targeting the lung microbiota may be a promising approach for preventing infections in critically ill patients.

Precursory worldwide signatures of earthquake occurrences on Swarm satellite data.

The study of the preparation phase of large earthquakes is essential to understand the physical processes involved, and potentially useful also to develop a future reliable short-term warning system. Here we analyse electron density and magnetic field data measured by Swarm three-satellite constellation for 4.7 years, to look for possible in-situ ionospheric precursors of large earthquakes to study the interactions between the lithosphere and the above atmosphere and ionosphere, in what is called the Lithosphere-Atmosphere-Ionosphere Coupling (LAIC). We define these anomalies statistically in the whole space-time interval of interest and use a Worldwide Statistical Correlation (WSC) analysis through a superposed epoch approach to study the possible relation with the earthquakes. We find some clear concentrations of electron density and magnetic anomalies from more than two months to some days before the earthquake occurrences. Such anomaly clustering is, in general, statistically significant with respect to homogeneous random simulations, supporting a LAIC during the preparation phase of earthquakes. By investigating different earthquake magnitude ranges, not only do we confirm the well-known Rikitake empirical law between ionospheric anomaly precursor time and earthquake magnitude, but we also give more reliability to the seismic source origin for many of the identified anomalies.

Bioelectronics goes 3D: new trends in cell-chip interface engineering.

Bioelectronic platforms can be used for electrophysiology, monitoring and stimulating specific cellular functions. While planar electroactive materials have been extensively used, in the past decade new approaches have focused on engineering the interface with pseudo-3D micro and nanostructures and, more recently, on 3D geometries (i.e. scaffold-like). Here, we present an overview of this transition from 2D to 3D bioelectronic platforms and our recent achievements of characterizing the interface between the cells and the device.

Optical absorption and magnetic circular dichroism spectra of thiouracils: a quantum mechanical study in solution.

The excited electronic states of 2-thiouracil, 4-thiouracil and 2,4-dithiouracil, the analogues of uracil where the carbonyl oxygens are substituted by sulphur atoms, have been investigated by computing the magnetic circular dichroism (MCD) and one-photon absorption (OPA) spectra at the time-dependent density functional theory level. Special attention has been paid to solvent effects, included by a mixed discrete/continuum model, and to determining how our results depend on the adopted DFT functional (CAM-B3LYP and B3LYP). Whereas including solvent effects does not dramatically impact the MCD and OPA spectra, though improving the agreement with the experimental spectra, the performances of CAM-B3LYP and B3LYP are remarkably different. CAM-B3LYP captures well the effect of thionation on the uracil excited states and provides spectra in good agreement with the experiments, whereas B3LYP shows some deficiency in describing 2-TU and 2,4-DTU spectra, despite being more accurate than CAM-B3LYP for 4-TU.

Ultra-thin resin embedding method for scanning electron microscopy of individual cells on high and low aspect ratio 3D nanostructures.

The preparation of biological cells for either scanning or transmission electron microscopy requires a complex process of fixation, dehydration and drying. Critical point drying is commonly used for samples investigated with a scanning electron beam, whereas resin-infiltration is typically used for transmission electron microscopy. Critical point drying may cause cracks at the cellular surface and a sponge-like morphology of nondistinguishable intracellular compartments. Resin-infiltrated biological samples result in a solid block of resin, which can be further processed by mechanical sectioning, however that does not allow a top view examination of small cell-cell and cell-surface contacts. Here, we propose a method for removing resin excess on biological samples before effective polymerization. In this way the cells result to be embedded in an ultra-thin layer of epoxy resin. This novel method highlights in contrast to standard methods the imaging of individual cells not only on nanostructured planar surfaces but also on topologically challenging substrates with high aspect ratio three-dimensional features by scanning electron microscopy.

Evaluation of trans-sphenoidal surgery in pituitary GH-secreting micro- and macroadenomas: a comparison between microsurgical and endoscopic approach.

AIM: Acromegaly is caused by a GH-secreting pituitary adenoma, associated with many comorbidities and increased risk of mortality. Surgery is the first-line therapy. Success of therapy is measured by symptomatic improvement, preservation of pituitary function and biochemical control. Trans-sphenoidal surgery (TSS), endoscopic or microscopic, is the preferred treatment. To evaluate surgery effectiveness and individuate the technique associated with a higher remission rate, patients undergoing TSS were retrospectively selected. METHODS: Thirty-seven consecutive patients underwent surgery between 1996 and 2006. Tumors were classified into macroadenomas or microadenomas and into intrasellar, extrasellar and extrasellar with cavernous sinus invasion. Surgery was performed in 22 patients with endoscopic technique, in 15 patients with microsurgical approach. The hormonal assays were performed 6 months and yearly after surgery for an average of 5 years. RESULTS: Ten patients were affected by microadenoma, 27 by macroadenoma. In microadenomas remission rate was independent of the used technique. Within macroadenomas, remission percentage in endoscopic approach (68.75%) was significantly higher than in microscopic approach (18.18%) (P=0.018). Postsurgical biochemical remission was calculated combining the surgical technique and tumor extension: the endoscopic approach was associated with a significantly higher remission rate in extrasellar than both in intrasellar and extrasellar with cavernous sinus invasion. In the latter group, any technique had not reached biochemical remission. CONCLUSION: TSS is able to induce a long-term remission of acromegaly, with low risk of recurrence and complications. Endoscopic approach is more suitable than microscopic technique in macroadenomas and adenomas with suprasellar extension.

Deformities of chironomid larvae and heavy metal pollution: from laboratory to field studies.

Mouthpart deformities of Chironomus riparius larvae (Diptera) have been investigated to evaluate the toxic effects of contamination by heavy metals in the Genna Stream (Central Italy), situated in an area subjected to intensive swine farms (40000 heads). The livestock farming (fertirrigation) contributes to metal pollution of the Genna Stream with an increase of copper, zinc, cadmium, chromium and nickel in the sediments of the downstream stations. The incidence of mentum deformities was very high at all sampling stations, about 56%. The highest values of deformities were found in the intermediate river reach (St. 3: 65%) and in March (66%), mainly due to an increase in severe deformities. The high incidence of severe deformities (30%) is attributed to the high pollution level by heavy metals in the sediments, in particular to copper and zinc, which showed the highest average value at St. 3 and in March. This field study reflected the relationships between sediment metal concentrations and chironomid mouthpart deformities, previously observed in laboratory tests, and highlighted these deformities as toxicity endpoints. This feature paves the way for their use as an effective tool in freshwater bioassessment monitoring programs to evaluate the toxic effects of metal contamination in freshwater ecosystems.

[Neonatal asphyxia: neurologic outcome]. / Prognosi neurologica dell'asfissia neonatale.

AIM: The neonatal asphyxia is recognized as an important cause of morbidity and mortality during the pediatric age. The objective of this study was to evaluate the correlation between some neonatal variables and neurological outcome at two years of life in infants with asphyxia, in order to produce a correct prognosis and to grant a rapid and targeted therapy. METHODS: We have recruited 63 patients whose history and neuroimages suggested a neonatal asphyxia, and we have analysed their clinical- instrumental parameters every three months until two years of life. A correlation study was carried out in order to find a statistical significance indicated by p-value < 0,05. The correlation was made by means of Chi-square and ANOVA (analysis of variance) test. RESULTS: Only one patient developed isolated epilepsy, 17 developed CP associated to epilepsy (14 of them were term infants, 3 were preterm); 25 patients, 13 term and 12 preterm, developed only CP; 20 patients, 11 preterm and 9 term infants, developed a psychomotor delay. The most severe clinical picture (CP associated with epilepsy) appeared in 12 infants of adequate weight and in 5 LBW children; the CP appeared in 14 NW patients, 5 LBW, 4 VLBW and 2 ELBW. Psychomotor delay was developed by 8 NW children, 2 LBW and 10 ELBW. Most patients with severe CP presented severe neurological symptoms at birth. Moderate CP involved those who had a mild neurological or systemic symptoms. Furthermore an association emerged between early epilepsy and CP onset and their severity. CONCLUSION: Neonatal seizures are not related to an increased risk to develop epilepsy. Epilepsy alone is a rare event and it usually complicates CP picture. Most subject with both epilepsy and CP are term infants with adequate weight. Preterm VLBW infants have a greater risk to develop a psychomotor delay. Clinical conditions at birth are related to CP severity (several neonatal neurological signs are the greater risk factors). Severely pathological neonatal EEG (background activity) is related to CP severity and an early symptomatic epilepsy onset is related with both epilepsy and CP severity.

Positive outcome of occlusal freeway space reestablishment in patients with medication overuse due to chronic migraine.

Considering the great chapter of migraines, it is important to note the signs and symptoms caused by an alteration of the relationship of the facial musculature and the occlusal freeway space (FWS) that is the distance from maximal intercuspation to the habitual rest position (measurable in 1.4-2.5 mm). To any mandible position changing (detected by periodontal, muscle and joint proprioceptors), there is an influence on the neuromuscular system and then an alteration of the FWS. A group of 60 patients with chronic migraine (CM) underwent a withdrawal of overused medication and were subjected to electromyographic and kinesiographic evaluation. All those who presented an alteration of the FWS at rest position have been subjected to treatment with orthosis device for about 12 months. The aim of our work is to obtain and define a correct mandibular position, physiological, in agreement with the neuromuscular structures of the patient. Clinical results obtained on this pool of patients, in terms of reduction of the VAS, let us understand the importance of the inviolability of the FWS and to eliminate any type of mandibular deviation with respect to the closure trajectory induced by TENS in patients suffering from CM.

Implementing gnathological and neuromuscular concepts in patients with chronic migraine.

Temporomandibular disorders are among the potential comorbidities of migraine, and recent reports showed that they may have a role in promoting its progression into chronic migraine (CM). In order to clarify the possible role of neuromuscular components of the stomatognathic system in patients with CM, we studied 18 patients admitted as inpatients at our Headache Unit to undergo a withdrawal protocol for medication overuse, who underwent orthosis, after clinical and instrumental gnathological evaluation. They were subsequently evaluated after 6 months. The values of electromyographic parameters as well as of pain outcomes showed a significant decrease after orthosis. The implementation of gnathological and neuromuscular concepts can have a relevant role in the management of CM patients, in the contest of a multidisciplinary approach.

Combined treatment of odontogenic keratocysts: initial marsupialization and successive enucleation with peripheral ostectomy plus Carnoy's solution application. A five-year follow-up experience.

AIM: The odontogenic keratocyst (KCOT) is a locally aggressive, cystic jaw lesion with a high growth potential and a propensity for recurrence. Considering its neoplastic features, treatments of keratocysts are required and they are generally classified as conservative or aggressive. However, although in literature there are several studies, the choice of treatment strategies remains controversial. We report a two-stage protocol based on initial marsupialization and successive enucleation. METHODS: Three cases of large KCOTs have been treated by initial marsupialization and, after a mean period of six months, successive enucleation with peripheral ostectomy and application of Carnoy's solution was performed. RESULTS: All patients were instructed in daily irrigation using chlorhexidine 0.2% during the period of marsupialization. After enucleation, good healing was obtained in all cases and from two up to five years of follow-up, there is no evidence of recurrence. CONCLUSION: Two-stage surgical treatment protocol of keratocyst leads to complete healing, preservation of important anatomical structures and absence of recurrence.

Use of fresh frozen bone graft in rehabilitation of maxillar atrophy.

AIM: Fresh frozen bone (FFB) is homologous bone obtained from human donors, provided by Tissue Banks. It is a graft material in reconstructive surgery; it is currently and widely used in orthopedic surgery and lately it has been introduced in oral and maxillofacial surgery. The purpose of this work was to show the use of fresh frozen homologous bone for bony augmentation of the maxilla and mandible in preparation for dental reconstruction with endosseous implants, as an effective alternative to harvesting and grafting autogenous bone from intra- or extra-oral donor sites. METHODS: The case presented clinically demonstrates the use of FFB grafts in the vertical augmentation of a severe maxillary atrophy in general anesthesia, and the outpatient treatment with implants insertion and prosthetic restoration. Histologic evaluation of graft biopsy six months after surgery is added to clinical assessments. RESULTS: Clinical outcome is shown with good volumetric and morphological reconstruction of the alveolar ridge without the need of a donor site. Excellent graft integration and bleeding newly formed bone was seen at the second surgical step (six months after FFB grafting), when fixation screws were removed and implant placement procedure was performed. CONCLUSION: The use of FFB in major preprosthetic surgery may be an acceptable therapeutic alternative to the autogenous block graft (harvested from iliac crest or calvarium) for its success rate as graft material. Benefits include: surgical procedure with reduced discomfort and infection risk as a second operation field to harvest the graft is avoided; FFB is safe, cheap and available in programmed amounts, its use can significantly reduce operating time.

Towards the realization of label-free biosensors through impedance spectroscopy integrated with IDES technology.

Impedance spectroscopy (IS) is a powerful technique for analysis of the complex electrical impedance of a large variety of biological systems, because it is sensitive both to surface phenomena and to changes of bulk properties. A simple and convenient method of analysis of cell properties by IS is described. An interdigitated electrodes configuration was used for the measurements; human epithelial cells were grown on the device to investigate the complex dielectric response as a function of frequency, in order to test the suitability of the device for use as a label-free biosensor. To test the ability of the device to detect channels in the cell membrane, the effect of drugs known to affect membrane integrity was also investigated. The frequency response of the admittance (i.e. the reciprocal of the impedance) can be well fitted by a model based on very simple assumptions about the cells coating the device surface and the current flow; from the calculations, membrane-specific capacitance and information about cell adhesion can be inferred. These preliminary efforts have shown that our configuration could lead to a label-free non-invasive technique for biosensing and cellular behavior monitoring which might prove useful in investigation of the basic properties of cells and the effect of drugs by estimation of some fundamental properties and modification of the electrical characteristics of the device.

Vibrationally Resolved Absorption and Emission Spectra of Dithiophene in the Gas Phase and in Solution by First-Principle Quantum Mechanical Calculations.

The absorption and emission spectra of dithiophene have been computed in different environments (gas phase, apolar, and polar solvents) and at different temperatures, including Duschinsky, temperature and solvent effects at full ab initio level, and considering the anharmonicity of the double well potential associated with the inter-ring torsional mode. The computed spectra are in very good agreement with the experimental ones, allowing for a complete assignment of the main vibrational features. Five different density functionals (BLYP, B3LYP, CAM-B3LYP, BHLYP, and PBE0) have been tested, and CAM-B3LYP and PBE0 are the most accurate.

Four-year clinical and neuroradiological follow-up of a papillary tumor of the pineal region.

Papillary tumor of the pineal region (PTPR) is a rare variety of CNS neoplasms and, since its first definition in 2003, only 64 cases have been described. PTPR is a primary neoplasm morphologically characterized by papillary structure staining for cytokeratin, transthyretin, neurone-specific enolase and S-100 protein. We report on a case of about 4 years' clinical history and neuroradiological follow-up of PTPR, in a 47-year-old Indian patient, with the aim of increasing the knowledge of its natural history. We describe through CT and MRI scans the natural evolution of this neoplasm, enhancing changes and morphologic structures involved, together with the final surgical treatment and pathological details. A mean growth rate average was calculated for this kind of lesion. In conclusion, the inexorable progressive growing nature of this tumor leads us to advocate an aggressive attitude among neurosurgeons and radiotherapists, with a precocious surgical approach when the suspicion rises.

[Procedural pain perception of preterm newborn in neonatal intensive care unit: assessment and non-pharmacological approaches]. / Percezione del dolore procedurale del nato pretermine in terapia intensiva neonatale: valutazione e tecniche non farmacologiche d'intervento.

AIM: The aim of this study was to evaluate the reaction to the procedural pain of preterm newborn and to demonstrate the different effectiveness of the two analgesic and not pharmacological techniques of recent clinical acquisition, the use of glucose solution and the sensorial saturation, in order to identify an optimal strategy for the prevention and pain treatment. METHODS: We take a sample of 28 preterm newborns of 30-35 weeks. The subjects are divided in two randomized groups following the kind of analgesia used during the hematic sample from heel: the first group (group A) included 14 subjects, who received glucose solution associated to no nutritive suction; the second group (group B) included 14 subjects who received the sensorial saturation. The symptoms associated with pain at the moment of venous sample are measured through premature infant pain profile (PIPP) scale. RESULTS: Results show that the score was lower in the group treated with sensorial saturation (media 6.52; P<0.001) than in the group treated with glucose (media 13.80; P<0.05). CONCLUSION: The use of "care" techniques (in our case sensorial saturation) ameliorates the quality of life in NICU and reduces the pain threshold perceived by newborn, reducing therefore the exposition to the pain stimulus and the possibility that some consequences due to an inadequate pain treatment in neonatal age could develop.

Chronic daily headache: suggestion for the neuromuscular oral therapy.

Tweny patients (M: 4, F: 16, mean age 37 ± 11 years) with diagnosis of chronic daily headache (CDH), after drug withdrawal, were under electromyography, kinesiography and masticatory muscle deprogramming by TENS to identify the physiological rest position of the mandible. Our purpose was to clarify a possible role of the neuromuscular stomatognathic system. Examinations showed that 17 patients needed a neuromuscular orthosis, an occlusal device, to provisionally correct the detected discrepancies of jaw position. Of those, the 10 patients who showed an occlusal sagittal discrepancy higher than 2 mm and/or a lateral deviation higher than 0.4 mm, associated with more than three parafunctional activities, had a meaningful decrease on frequency/intensity of migraine crisis and/or of days of headache. VAS pain score during crisis decreased from 9.0 ± 0.9 to 4.9 ± 2.7; frequency of crisis were from 20.7 ± 5.2 to 9.5 ± 7.7. Baseline pain were from 5.3 ± 1.2 to 3.0 ± 1.3. Satisfying clinical results can be reached combining behavioural education and neuromuscular orthosis. This can be very helpful in patients who show significant discrepancy of jaw position that only TENS deprogramming can reveal and kinesiography can detect with such accuracy.