Analgesic effectiveness and tolerability of oral oxycodone/naloxone and pregabalin in patients with lung cancer and neuropathic pain. An observational analysis

INTRODUCTION: Cancer-related pain has a severe negative impact on quality of life. Combination analgesic therapy with oxycodone and pregabalin is effective for treating neuropathic cancer pain. We investigated the efficacy and tolerability of a dose-escalation combination therapy with prolonged-release oxycodone/naloxone (OXN-PR) and pregabalin in patients with non-small-cell lung cancer and severe neuropathic pain. METHODS: This was a 4-week, open-label, observational study. Patients were treated with OXN-PR and pregabalin. Average pain intensity ([API] measured on a 0-10 numerical rating scale) and neuropathic pain (Douleur Neuropathique 4) were assessed at study entry and at follow-up visits. The primary endpoint was response to treatment, defined as a reduction of API at T28 ≥30% from baseline. Secondary endpoints included other efficacy measures, as well as patient satisfaction and quality of life (Brief Pain Inventory Short Form), Hospital Anxiety and Depression Scale, and Symptom Distress Scale; bowel function was also assessed. RESULTS: A total of 56 patients were enrolled. API at baseline was 8.0±0.9, and decreased after 4 weeks by 48% (4.2±1.9; P<0.0001 vs baseline); 46 (82.1%) patients responded to treatment. Significant improvements were also reported in number/severity of breakthrough cancer pain episodes (P=0.001), Brief Pain Inventory Short Form (P=0.0002), Symptom Distress Scale (P<0.0001), Hospital Anxiety and Depression Scale depression (P=0.0006) and anxiety (P<0.0001) subscales, and bowel function (P=0.0003). At study end, 37 (66.0%) patients were satisfied/very satisfied with the new analgesic treatment. Combination therapy had a good safety profile. CONCLUSION: OXN-PR and pregabalin were safe and highly effective in a real-world setting of severe neuropathic cancer pain, with a high rate of satisfaction, without interference on bowel function

Allergenic power reduction of food proteins by nonthermal technologies

2013 - 2014The great interest of the research activity in food allergies could be attributed to the increase of allergic reactions all over the world not only in infants but even in adult age. As an alternative to the development of an allergen-free diet, many works have been focused on a novel approach for the treatment of allergens: instead of eliminating the allergens from the diet, the immunoresponse can be reduced or even eliminated by inducing some modifications of their molecular structure. In fact, changes in allergen conformation can modulate its identification by the specific antibody produced by immune system in allergic reactions. Structural modifications in allergens could be induced by conventional thermal treatments as well as by non-thermal technologies, namely High Hydrostatic Pressure (HHP), Pulsed Electric Fields (PEF), Pulsed Light (PL) and -radiations. Non-thermal technologies have been widely used in the last years for food preservation, having the advantage of increasing the shelf-life and freshness of the raw food products. These technologies are able to affect the food nutritional and organoleptic properties only slightly thanks to the use of a non-thermal stress to treat foodstuffs. Among them High Hydrostatic Pressure technology has been successfully used in food pasteurization, but also in processes involving the sol-gel transition such as the production of jams, jellies and dairy products. The ability of High Pressure to determine structural changes in foods was studied in order to assess if proteins unfolding and/or aggregation and gelation can be induced and if the treatment affects the functional properties and digestibility of proteins. These effects were studied on particular proteins, namely the allergens, for which unfolding and structural modification have been proven. However, the effectiveness of the High Pressure processing on the reduction of immunoresponse reduction was not clearly assessed so far. The objective of this PhD thesis was the study of the modifications induced by High Pressure Process on allergenic proteins and the possibility of obtaining hypoallergenic peptides by means of a combined High Hydrostatic Pressure hydrolysis. In particular, the effect of the HHP on the allergens structural modification was investigated in a wide range of operating conditions, including both gelling and ungelling conditions. Rheological behavior and functional properties of HHP processed allergens was also determined. [edited by Author]XIII n.s

CRP Predicts Safe Patient Discharge after Colorectal Surgery. Reply

Reply: We would like to thank Aurelie´n Dupre`, Johan Gagnie´r, Heloı¨se Samba, Michel Rivoire, and Karem Slim for their comments about our article ‘‘Procalcitonin Reveals Early Dehiscence in Colorectal Surgery: The PREDICS Study.’’1 It is very rewarding to realize that this paper is stimulating so many observations, this means thatwe are talking about an interesting topic

Study of the effects of High Hydrostatic Pressure (HHP) and Pulsed Light (PL) on BSA structure and hydrolysis

Non-thermal technologies, such as High Hydrostatic Pressure (HHP) and Pulsed light (PL), affect protein inducing modifications in its conformational structure. For this reason the hydrolysis reaction of the protein can be modulated if it is conducted in combination with these technologies which are able to change the availability of peptide bonds exposed to the enzymatic action. The aim is to study the effects of HHP and PL on the structure and the extent of hydrolysis reaction of a target protein: the Bovine Serum Albumin (BSA). BSA protein (5 mg/mL) in sodium phosphate buffer (50 mM, pH = 8) were treated with PL and HHP at different processing conditions, namely pressure level and treatment time in the case of HHP and treatment time and energy input in the case of PL. Structural modification of the protein solutions were analyzed by determining the sulphidrilic groups and the changes of the secondary structure. The effect of the two treatments on the hydrolysis degree (HD) at 37 °C was also evaluated by OPA method. Chymotrypsin and trypsin (E/S ratio = 1/10) were used to hydrolyze the BSA protein solutions. The hydrolysis was carried out in HHP assisted or PL assisted conditions or the protein solutions were treated with HHP or PL processes and immediately after hydrolyzed with the enzymes. Results obtained so far demonstrated that the two technologies tested are able to induce protein modifications and the occurrence and importance of this phenomenon depends on processing parameters causing protein unfolding, namely pressure level and number of pulses. When the maximum protein unfolding is obtained, higher HD values are detected. The highest HD value is obtained in HHP assisted hydrolysis with longer treatment time, and when, before undergoing hydrolysis, the PL treatment is applied to the solution placed at the higher distance from the lamp

Transcriptome-wide identification and expression analysis of DIVARICATA- and RADIALIS-like genes of the Mediterranean orchid Orchis italica.

Bilateral symmetry of flowers is a relevant novelty that has occurred many times throughout the evolution of flowering plants. In Antirrhinum majus, establishment of flower dorso-ventral asymmetry is mainly due to interaction of TCP (CYC and DICH) and MYB (DIV, RAD and DRIF) transcription factors. In the present study, we characterized 8 DIV-, 4 RAD- and 2 DRIF-like genes from the transcriptome of Orchis italica, an orchid species with bilaterally symmetric and resupinate flowers. We found a similar number of DIV- and RAD-like genes within the genomes of Phalaenopsis equestris and Dendrobium catenatum orchids. Orchid DIV- and RAD-like proteins share conserved motifs whose distribution reflects their phylogeny and analysis of the genomic organization revealed a single intron containing many traces of transposable elements. Evolutionary analysis has shown that purifying selection acts on the DIV- and RAD-like coding regions in orchids, with relaxation of selective constraints in a branch of the DIV-like genes. Analysis of the expression patterns of DIV- and RAD-like genes in O. italica revealed possible redundant functions for some of them. In the perianth of O. italica, the ortholog of DIV and DRIF of A. majus are expressed in all tissues, whereas RAD is mainly expressed in the outer tepals and lip. These data allow for proposal of an evolutionary conserved model in which the expression of the orthologs of the DIV, RAD and DRIF genes might be related to establishment of flower bilateral symmetry in the non-model orchid species O. italica

Bilateral 5 Hz transcranial alternating current stimulation on fronto-temporal areas modulates resting-state EEG

Rhythmic non-invasive brain stimulations are promising tools to modulate brain activity by entraining neural oscillations in specific cortical networks. The aim of the study was to assess the possibility to influence the neural circuits of the wake-sleep transition in awake subjects via a bilateral transcranial alternating current stimulation at 5 Hz (theta-tACS) on fronto-temporal areas. 25 healthy volunteers participated in two within-subject sessions (theta-tACS and sham), one week apart and in counterbalanced order. We assessed the stimulation effects on cortical EEG activity (28 derivations) and self-reported sleepiness (Karolinska Sleepiness Scale). theta-tACS induced significant increases of the theta activity in temporo-parieto-occipital areas and centro-frontal increases in the alpha activity compared to sham but failed to induce any online effect on sleepiness. Since the total energy delivered in the sham condition was much less than in the active theta-tACS, the current data are unable to isolate the specific effect of entrained theta oscillatory activity per se on sleepiness scores. On this basis, we concluded that theta-tACS modulated theta and alpha EEG activity with a topography consistent with high sleep pressure conditions. However, no causal relation can be traced on the basis of the current results between these rhythms and changes on sleepines

Pullulan for advanced sustainable body- and skin-contact applications

The present review had the aim of describing the methodologies of synthesis and properties of biobased pullulan, a microbial polysaccharide investigated in the last decade because of its interesting potentialities in several applications. After describing the implications of pullulan in nano-technology, biodegradation, compatibility with body and skin, and sustainability, the current applications of pullulan are described, with the aim of assessing the potentialities of this biopolymer in the biomedical, personal care, and cosmetic sector, especially in applications in contact with skin

Lu5Pd4Ge8 and Lu3Pd4Ge4: Two more germanides among polar intermetallics

In this study, two novel Lu5Pd4Ge8and Lu3Pd4Ge4polar intermetallics were prepared by direct synthesis of pure constituents. Their crystal structures were determined by single crystal X-ray diffraction analysis: Lu5Pd4Ge8is monoclinic, P21/m, mP34, a = 5.7406(3), b = 13.7087(7), c = 8.3423(4) \uc5, \u3b2 = 107.8(1), Z = 2; Lu3Pd4Ge4is orthorhombic, Immm, oI22, a = 4.1368(3), b = 6.9192(5), c = 13.8229(9) \uc5, Z = 2. The Lu5Pd4Ge8analysed crystal is one more example of non-merohedral twinning among the rare earth containing germanides. Chemical bonding DFT studies were conducted for these polar intermetallics and showing a metallic-like behavior. Gathered results for Lu5Pd4Ge8and Lu3Pd4Ge4permit to described both of them as composed by [Pd\u2013Ge]\u3b4\u2013three dimensional networks bonded to positively charged lutetium species. From the structural chemical point of view, the studied compounds manifest some similarities to the Zintl phases, containing well-known covalent fragment i.e., Ge dumbbells as well as unique cis-Ge4units. A comparative analysis of molecular orbital diagrams for Ge26\u2013and cis-Ge10\u2013anions with COHP results supports the idea of the existence of complex Pd\u2013Ge polyanions hosting covalently bonded partially polarised Ge units. The palladium atoms have an anion like behaviour and being the most electronegative cause the noticeable variation of Ge species charges from site to site. Lutetium charges oscillate around +1.5 for all crystallographic positions. Obtained results explained why the classical Zintl-Klemm concept can\u2019t be applied for the studied polar intermetallics

Investigation on neurobiological mechanisms of dreaming in the new decade

Dream research has advanced significantly over the last twenty years, thanks to the new applications of neuroimaging and electrophysiological techniques. Many findings pointed out that mental activity during sleep and wakefulness shared similar neural bases. On the other side, recent studies have highlighted that dream experience is promoted by significant brain activation, characterized by reduced low frequencies and increased rapid frequencies. Additionally, several studies confirmed that the posterior parietal area and prefrontal cortex are responsible for dream experience. Further, early results revealed that dreaming might be manipulated by sensory stimulations that would provoke the incorporation of specific cues into the dream scenario. Recently, transcranial stimulation techniques have been applied to modulate the level of consciousness during sleep, supporting previous findings and adding new information about neural correlates of dream recall. Overall, although multiple studies suggest that both the continuity and activation hypotheses provide a growing understanding of neural processes underlying dreaming, several issues are still unsolved. The impact of state-/trait-like variables, the influence of circadian and homeostatic factors, and the examination of parasomnia-like events to access dream contents are all opened issues deserving further deepening in future research