Preliminary results of a program for the implementation of laparoscopic colorectal surgery in an Italian comprehensive cancer center during the COVID-19 pandemic.

Despite operative benefit and oncological non-inferiority, videolaparoscopic (VLS) colorectal surgery is still relatively underutilized. This study analyzes the results of a program for the implementation of VLS colorectal surgery started in an Italian comprehensive cancer center shortly before COVID-19 outbreak. A prospective database was reviewed. The study period was divided in four phases: Phase-1 (Open surgery), Phase-2 (Discretional phase), Phase-3 (VLS implementation phase), and Phase-4 (VLS consolidation phase). Formal surgical and perioperative protocols were adopted from Phase-3. Postoperative complications were scored by the Clavien-Dindo classification. 414 surgical procedures were performed during Phase-1, 348 during Phase-2, 360 during Phase-3, and 325 during Phase-4. In the four phases, VLS primary colorectal resections increased from 11/214 (5.1%), to 55/163 (33.7%), 85/151 (57.0%), and 109/147 (74.1%), respectively. The difference was statistically significant (P < 0.001). All-type VLS procedures were 16 (3.5%), 61 (16.2%), 103 (27.0%), and 126 (38.6%) (P < 0.001). Conversions to open surgery of attempted laparoscopic colorectal resections were 17/278 in the overall series (6.1%), and 12/207 during Phase-3 and Phase-4 (4.3%). Severe (grades IIIb-to-V) postoperative complications of VLS colorectal resections were 9.1% in Phase-1, 12.7% in Phase-2, 12.8% in Phase-3, and 5.3% in Phase-4 (P = 0.677), with no significant differences with open resections in each of the four phases: 9.4% (P = 0.976), 11.1% (P = 0.799), 13.8% (P = 1.000), and 8.3% (P = 0.729). Despite the difficulties deriving from the COVID-19 outbreak, our experience suggests that volume of laparoscopic colorectal surgery can be significantly and safely increased in a specialized surgical unit by means of strict operative protocols.

Endotypes of pollen-food syndrome in children with seasonal allergic rhinoconjunctivitis: a molecular classification.

BACKGROUND: Pollen-food syndrome (PFS) is heterogeneous with regard to triggers, severity, natural history, comorbidities, and response to treatment. Our study aimed to classify different endotypes of PFS based on IgE sensitization to panallergens. METHODS: We examined 1271 Italian children (age 4-18 years) with seasonal allergic rhinoconjunctivitis (SAR). Foods triggering PFS were acquired by questionnaire. Skin prick tests were performed with commercial pollen extracts. IgE to panallergens Phl p 12 (profilin), Bet v 1 (PR-10), and Pru p 3 (nsLTP) were tested by ImmunoCAP FEIA. An unsupervised hierarchical agglomerative clustering method was applied within PFS population. RESULTS: PFS was observed in 300/1271 children (24%). Cluster analysis identified five PFS endotypes linked to panallergen IgE sensitization: (i) cosensitization to ≥2 panallergens ('multi-panallergen PFS'); (ii-iv) sensitization to either profilin, or nsLTP, or PR-10 ('mono-panallergen PFS'); (v) no sensitization to panallergens ('no-panallergen PFS'). These endotypes showed peculiar characteristics: (i) 'multi-panallergen PFS': severe disease with frequent allergic comorbidities and multiple offending foods; (ii) 'profilin PFS': oral allergy syndrome (OAS) triggered by Cucurbitaceae; (iii) 'LTP PFS': living in Southern Italy, OAS triggered by hazelnut and peanut; (iv) 'PR-10 PFS': OAS triggered by Rosaceae; and (v) 'no-panallergen PFS': mild disease and OAS triggered by kiwifruit. CONCLUSIONS: In a Mediterranean country characterized by multiple pollen exposures, PFS is a complex and frequent complication of childhood SAR, with five distinct endotypes marked by peculiar profiles of IgE sensitization to panallergens. Prospective studies in cohorts of patients with PFS are now required to test whether this novel classification may be useful for diagnostic and therapeutic purposes in the clinical practice.

The smartphone: a novel diagnostic tool in pollen allergy?

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Nacre extract restores the mineralization capacity of subchondral osteoarthritis osteoblasts.

Osteoarthritis (OA) is the most common cause of joint chronic pain and involves the entire joints. Subchondral osteoarthritic osteoblasts present a mineralization defect and, to date, only a few molecules (Vitamin D3 and Bone Morphogenetic Protein2) could improve the mineralization potential of this cell type. In this context, we have tested for the first time the effect of nacre extract on the mineralization capacity of osteoblasts from OA patients. Nacre extract is known to contain osteogenic molecules which have demonstrated their activities notably on the MC3T3 pre-osteoblastic cell line. For this goal, molecules were extracted from nacre (ESM, Ethanol Soluble Matrix) and tested on osteoblasts of the subchondral bone from OA patients undergoing total knee replacement and on MC3T3 cells for comparison. We chose to investigate the mineralization with Alizarin Red staining and with the study of extracellular matrix (ECM) structure and composition. In a complementary way the structure of the ECM secreted during the mineralization phase was investigated using second harmonic generation (SHG). Nacre extract was able to induce the early presence (after 7 days) of precipitated calcium in cells. Raman spectroscopy and electron microscopy showed the presence of nanograins of an early crystalline form of calcium phosphate in OA osteoblasts ECM and hydroxyapatite in MC3T3 ECM. SHG collagen fibers signal was present in both cell types but lower for OA osteoblasts. In conclusion, nacre extract was able to rapidly restore the mineralization capacity of osteoarthritis osteoblasts, therefore confirming the potential of nacre as a source of osteogenic compounds.

The effect of palm oil addition to the diet of dairy sheep on the immune response.

The aim of this study was to evaluate whether a diet based on palm oil has any influence on the immune response and on the number of eggs per gram of faeces (EPG) of gastrointestinal nematodes (GIN) in dairy sheep. To address this issue, 30 ewes in early lactation were confined and divided into three groups (n = 10) receiving a daily isoproteic and isoenergetic diet. Palm oil was added to the feed at different concentrations: 0% (control; group A), 4% (group B) and 6% (group C). The animals were treated with levamisole 10 days before the beginning of the experiment. Faecal samples were collected and analysed for EPG on day zero of the experiment. On days 60 and 120, individual faecal and blood samples were collected, and the FAMACHA(©) score for assessing clinical anaemia was carried out. The groups receiving palm oil showed a significant reduction in EPG in relation to the control group (A) on day 120. Serum immunoglobulin levels (IgG, IgM and IgE) and proinflammatory cytokine levels (TNF-α, IL-1 and IL-6) were significantly increased on days 60 and 120 (p < 0.05) in groups B and C. Therefore, these results suggest that palm oil stimulates the immune response in sheep, thus reducing EPG of GIN. The hypothesis that palm oil has direct anthelmintic activity should be tested in future studies.

From neurovascular coupling to neurovascular cascade: a study on neural, autonomic and vascular transients in attention.

Mental processes bring about neural, vascular and autonomic changes in the brain cortex. Due to the different nature of these modifications, their onsets show no synchrony and time dynamics is often strongly dissimilar. After acquiring data from a group of 16 subjects, we estimated temporal correlation between task and signals in order to assess possible influences induced by an attentive task on electroencephalographic (EEG), heart rate variability (HRV), oxy- and deoxy-haemoglobin concentration signals. We also investigated correlations and time delays between couples of different biological signals. This allowed for the isolation of a subgroup of subjects showing similar tracks. Cardiac frequency and deoxy-haemoglobin signals displayed a strong positive correlation with the task design, while EEG alpha rhythm and oxygenation showed a negative correlation. Neural electrical response was nearly instantaneous with respect to the task progression, and autonomic response showed a mean delay of about 15 s and a slower hemodynamic response (mean delay above 20 s) was finally induced. Globally, the task elicited a cascade of responses, in which delays can be quantified.

Rosaceae-associated exercise-induced anaphylaxis with positive SPT and negative IgE reactivity to Pru p 3.

BACKGROUND: Food-dependent-exercise-induced anaphylaxis (FDEIA) is characterized by anaphylactic symptoms after exercise following ingestion of food. We present a case of FDEIA induced by Rosacee fruits showing some diagnostic problems. MATERIAL AND METHODS: A 12 years-old boy with seasonal allergy to olive and cypressus pollens, experienced two distinct episodes of FDEIA, grade 4 and 3 of the Sampson Scale respectively, during intense exercise, about 30 minutes after eating a peach with peel or some cherries. SPT with commercial peach extract and fresh Rosacee fruits scored positive while SPT with a date palm profilin-enriched extract was negative. On in vitro tests total IgE were 44 kU/l and IgE for peach, cherry, Prup 3, Prup 1, Bet v 1, Bet v 2, Bet v 4 were negative. SPT with Prup 3 UniCAP device (cellulose polymer in a plastic reserve highly binding allergen protein) was negative. An oral food challenge, performed at rest using a commercial peach juice, scored negative. An immunoblot analysis performed with peach extract was negative. DISCUSSION: The main peculiarity of this case of FDEIA is the discrepancy between positive SPT and negative in-vitro findings. The positive SPT with the commercial peach extract suggested hypersensitivity to lipid transfer protein; however, no IgE reactivity to rPrup 3 was found in-vitro. The negative immunoblot analysis, possibly caused by the low levels of specific IgE, did not allow us to investigate the nature of the relevant allergen protein further. It is possible that this patient reacted to a different peach allergen or, alternatively, that he recognized an isoform of LTP that is different fr-om that in Uni-CAP. CONCLUSION: This case emphasizes once more the diagnostic relevance of SPT with extracts and fresh material to be performed before investigating IgE reactivity to single allergen components in-vitro.

Rationale and clinical results of multi-target treatments in oncology.

During the last 10 years, the concept of targeted biological therapy for the treatment of cancer has emerged. Targeted agents entered clinical practice only recently, and the first drugs with demonstrated clinical efficacy were mainly inhibitors of the ErbB family of receptors (i.e., EGFR and HER-2), either monoclonal antibodies (MAbs) or tyrosine kinase inhibitors (TKIs). After the proof of concept for the clinical efficacy and tolerability of these selective agents, it was conceived that most tumors will depend on more than one signaling pathway for their growth and survival. As a consequence, different strategies were pursued to inhibit multiple signaling pathways or multiple steps in the same pathway, either by the development of multi-targeted agents or the combination of single targeted drugs. The recent FDA and EMEA approval of sorafenib and sunitinib, both multi-targeted TKIs, marked the coming of age of this new generation of drugs. Now a whole new wave of multi-targeted compounds is moving into clinical trials, raising in the minds of investigators important questions about the best strategies to pursue in their use and many doubts about their differences and the seeming redundancies in the pipelines of pharmaceutical companies. This review will deal with the rationale underlying the multi-targeted approach and with the available clinical experience with multi-targeted agents, especially focusing on molecules with anti- EGFR mechanisms of action.

Intra-specific biodiversity of Italian myrtle (Myrtus communis) through chemical markers profile and biological activities of leaf methanolic extracts.

Methanolic extracts of Myrtus communis leaves from two Italian regions (Calabria and Sardinia) were processed to determine the content of myrtenol, linalool and eucalyptol. Among the Calabrian and Sardinian myrtle samples, linalool and eucalyptol chemotypes were prevalent. The extracts were also tested for antioxidant, antibacterial and antifungal activities. Myrtle leaves samples were dried and extracted through maceration. Partition chromatography was adopted to separate myrtenol, linalool and eucalyptol fractions. Analyses were performed through GC and GC-MS. Some of the samples showed a good scavenger activity evidenced by DPPH radical scavenging assay and beta-carotene bleaching test. Antibacterial and antifungal activities were generally weak. The phytochemical and biological characterization of all the extracts were determined with an aim to characterize the intra-specific biodiversity of myrtle populations.

[Anaesthetic preoperative assessment of chronic medications and herbal medicine use: a multicenter survey]. / Traitement médicamenteux et phytothérapie des patients adressés en consultation d'anesthésie: enquête multicentrique.

OBJECTIVE: This study was undertaken to quantify the use of chronic medication and herbal remedies in the presurgical population. STUDY DESIGN: Prospective multicenter survey. PATIENTS AND METHODS: Adult patients presenting for anaesthesia were directly asked if they were currently using chronic medication or herbal remedies. RESULTS: Among 1057 patients (age 54+/-17 yrs, woman 54%, ASA 2 [1-4], 74%) were taking one or more chronic medication. The most commonly used treatments were, in descending order angiotensin-converting enzyme inhibitors and angiotensin-II receptor blockers (15%), beta blockers (11%) and platelet inhibitors (10%). Also, 9% were taking one or more of the following herbal remedies known to interact with the perioperative period: valeriane, ginseng, ginkgo, St John's wort, echinacea and ephedra. Women and patients aged 40-70 yr were most likely to be taking a herbal product (p<0.001 and p<0.01 respectively). CONCLUSION: Chronic medication and herbal remedies are common in patients presenting for anaesthesia. Because of the potential interactions between anaesthetic drugs or techniques and such medication it is important for anaesthetists to be aware of their use.

Comparative screening of plant essential oils: phenylpropanoid moiety as basic core for antiplatelet activity.

Essential oils extracted from different plants (Anthemis nobilis L., Artemisia dracunculus L., Cannabis sativa L., Cupressus sempervirens L., Cymbopogon citratus (DC.) Stapf., Curcuma longa L., Foeniculum vulgare L., Hypericum perforatum L., Hyssopus officinalis L., Mentha spicata L., Monarda didyma L., Ocimum basilicum L., Ocotea quixos Kosterm., Origanum vulgare L., Pinus nigra J.F. Arnold, Pinus silvestris L., Piper crassinervium Kunth., Rosmarinus officinalis L., Salvia officinalis L., Salvia sclarea L., Santolina chamaecyparissus L., Thymus vulgaris L., Zingiber officinaie L.) were screened in guinea pig and rat plasma in order to assess antiplatelet activity and inhibition of clot retraction. The oils were chemically analysed and a relationship between components and ability to affect hemostasis was evidenced. O. quixos, F. vulgaris, and A. dracunculus showed the highest antiplatelet activity against ADP, Arachidonic Acid and the Thromboxane A2 agonist U46619 (IC50, 4-132 microg ml(-1)), and a good ability to destabilize clot retraction (IC50, 19-180 microg ml(-1)). For these oils a significant correlation between antiplatelet potency and phenylpropanoids content (54-86%) was evidenced thus suggesting a key role for this moiety in the prevention of clot formation. These findings provide the rationale to take in account the antiplatelet activity in the pharmacological screening of natural products containing phenylpropanoids.

Influence of environmental factors on composition of volatile constituents and biological activity of Helichrysum italicum (Roth) Don (Asteraceae).

The biovariability of Helichrysum italicum (Roth) Don grown wild in Calabria and Sardinia (Italy) was reported. This species has been characterized through the detection, isolation and quantitative evaluation of chemical markers (alpha-terpinolene, trans-cariophyllene and neryl acetate) by GC and GC-MS. Antioxidant activity of the methanolic H. italicum extracts using DPPH and beta-carotene bleaching test showed that the Calabrian samples were more active than those from Sardinia. The antibacterial activity of all extracts evidenced the best performance on the Gram positive bacteria particularly on Micrococcus luteus. Moreover, antifungal activity of all extracts was also tested evidencing important results particularly on the phytopathogene fungus Pythium ultimum. In general, as regards the antifungal activity, the extracts from Sardinia were more active than those from Calabria. The phytochemical analysis and the biological activity data suggested a possible use of these plant matrices in alimentary, cosmetic and pharmaceutical fields.

Comparative chemical composition and variability of biological activity of methanolic extracts from Hypericum perforatum L.

The biovariability of Hypericum perforatum L. (St. John's Wort) grown wild in Calabria and Sardinia (Italy) was reported with the aim to characterize the species through the isolation, detection, and quantitative evaluations of chemical markers (hypericin, quercetin, rutin) by HPLC analysis. Antioxidant activity of the methanolic H. perforatum extracts showed that the Calabrian samples were more active than those from Sardinia. The antibacterial activity evidenced the best performance on the gram positive bacteria with a MIC value of 50 microg/mL. Moreover, antifungal activity of all the extracts was also tested which showed interesting results particularly on the phytopathogene fungus P. ultimum. The variability shown by the samples could be attributed to environmental factors such as chemical-physical properties, composition of the soil, geographical coordinate, altitude, and solar exposure. The phytochemical analysis and the biological activity data suggested a possible use of H. perforatum extracts in the alimentary, cosmetic, and pharmaceutical fields.

Antinociceptive and gastroprotective effects of inhaled and orally administered Lavandula hybrida Reverchon "Grosso" essential oil.

In this study the antinociceptive and the gastroprotective effects of orally administered or inhaled Lavandula hybrida Reverchon "Grosso" essential oil, and its principal constituents linalool and linalyl acetate were evaluated in rodents. Either when orally administered (100 mg/kg) or inhaled for 60 min lavender essential oil significantly reduced the acetic acid-writhing response in a naloxone-sensitive manner. In the hot plate test, analgesic activity observed after oil inhalation was inhibited by naloxone, atropine, mecamylamine pretreatment suggesting the involvement of opioidergic as well as cholinergic pathways. Regardless of the administration route and the experimental model used both linalool and linalyl acetate did not produce significant analgesic response. Oral or inhalatory treatment with analgesic doses of essential oil did not affect mice spontaneous locomotor activity. Concerning the gastric effects, lavender oil, linalool and linalyl acetate oral administration protected against acute ethanol-induced gastric ulcers but did not prevent indomethacin-induced lesions indicating no interference with arachidonic acid metabolic cascade. In conclusion, besides this gastroprotection, lavender oil reveals an interesting analgesic activity mainly relevant after inhalation, at doses devoid of sedative side effect, suggesting the interest for potential application of this oil in aromatherapy.

Rhythm-specific pharmacological modulation of subthalamic activity in Parkinson's disease.

The subthalamic nucleus (STN) has a key role in the pathophysiology of Parkinson's disease and is the primary target for high-frequency deep brain stimulation (DBS). The STN rest electrical activity in Parkinson's disease, however, is still unclear. Here we tested the hypothesis that pharmacological modulation of STN activity has rhythm-specific effects in the classical range of EEG frequencies, below 50 Hz. We recorded local field potentials (LFPs) through electrodes implanted in the STN of patients with Parkinson's disease (20 nuclei from 13 patients). After overnight withdrawal of antiparkinsonian therapy, LFPs were recorded at rest both before (off) and after (on) acute administration of different antiparkinsonian drugs: levodopa, apomorphine, or orphenadrine. In the off-state, STN LFPs showed clearly defined peaks of oscillatory activity below 50 Hz: at low frequencies (2-7 Hz), in the alpha (7-13 Hz), low-beta (13-20 Hz), and high-beta range (20-30 Hz). In the on-state after levodopa and apomorphine administration, low-beta activity significantly decreased and low-frequency activity increased. In contrast, orphenadrine increased beta activity. Power changes elicited by levodopa and apomorphine at low frequencies and in the beta range were not correlated, whereas changes in the alpha band, which were globally not significant, correlated with the beta rhythm (namely, low beta: 13-20 Hz). In conclusion, in the human STN, there are at least two rhythms below 50 Hz that are separately modulated by antiparkinsonian medication: one at low frequencies and one in the beta range. Multiple rhythms are consistent with the hypothesis of multiple oscillating systems, each possibly correlating with specific aspects of human STN function and dysfunction.

The subthalamic nucleus in Parkinson's disease: power spectral density analysis of neural intraoperative signals.

To test a new tool for the neurophysiological identification of the human subthalamic nucleus (STN) during stereotactic surgery for the implantation of deep-brain-stimulation (DBS) electrodes, we analysed off-line the intraoperative signals recorded from patients with Parkinson's disease. We estimated the power spectral density (PSD) along each penetration track (8 patients, 13 sides) and determined the spatial correlation of the PSD with the target location estimated from neuroimaging procedures ("anatomical target"), and with the final target location derived from standard intraoperative neurophysiological procedures for STN localization ("clinical target"). At each step we recorded the 'on-line' signal for 120 seconds; because the PSD was estimated by calculating the periodogram for 6-second epochs of neural signal, we had 20 epochs at each step. When the electrode track crossed the STN, the PSD in the 0.25-2.5 kHz band increased, peaking on average <0.5 mm cranial to the clinical target and 1.00+/-1.51 mm caudal to the anatomical target. When the track was outside the nucleus, the PSD remained unchanged. Even on recordings with low signal-to-noise ratio, off-line PSD analysis of neural signals showed a good correspondence with the target indicated by the surgical team. On-line intraoperative estimation of the PSD may be a simple, reliable, rapid and complementary approach to electrophysiological monitoring during STN surgery for Parkinson's disease.

Novel antiplatelet and antithrombotic activities of essential oil from Lavandula hybrida Reverchon "grosso".

Lavender extracts are known to produce several mild effects at central and peripheral level. However, no studies are so far available about the potential effects of lavender essential oil on the hemostatic system. In this work, we demonstrated antiplatelet properties of lavender oil towards platelet aggregation induced by arachidonic acid, U46619, collagen and ADP (IC50 = 51, 84, 191 and 640 microg/ml, respectively) on guinea-pig platelet rich plasma (PRP) and its ability to destabilize clot retraction (IC50 = 149 microg/ml) induced by thrombin on rat PRP. Furthermore, antithrombotic properties were studied in an in vivo model of pulmonary thromboembolism induced by intravenous injection of a collagen-epinephrine mixture in mice subacutely treated with lavender oil. In this model, lavender oil (100 mg/kg/day os for 5 days) significantly reduced thrombotic events without inducing prohemorrhagic complications at variance with acetylsalicylic acid used as reference drug. Finally, main components of the oil were studied in vitro in order to assess their antiplatelet effects, but none of them possessed an activity comparable to the oil itself. These results provide the first experimental evidence of lavender oil's antiplatelet/antithrombotic properties which could be due to a synergistic effect of its components.

Bulk band gaps in divalent hexaborides.

Complementary angle-resolved photoemission and bulk-sensitive k-resolved resonant inelastic x-ray scattering of divalent hexaborides reveal a >1 eV X-point gap between the valence and conduction bands, in contradiction to the band overlap assumed in several models of their novel ferromagnetism. This semiconducting gap implies that carriers detected in transport measurements arise from defects, and the measured location of the bulk Fermi level at the bottom of the conduction band implicates boron vacancies as the origin of the excess electrons. The measured band structure and X-point gap in CaB6 additionally provide a stringent test case for many-body quasiparticle band calculations.

Movement-related modulation of neural activity in human basal ganglia and its L-DOPA dependency: recordings from deep brain stimulation electrodes in patients with Parkinson's disease.

Through electrodes implanted for deep brain stimulation in three patients (5 sides) with Parkinson's disease, we recorded the electrical activity from the human basal ganglia before, during and after voluntary contralateral finger movements, before and after L-DOPA. We analysed the movement-related spectral changes in the electroencephalographic signal from the subthalamic nucleus (STN) and from the internal globus pallidus (GPi). Before, during and after voluntary movements, signals arising from the human basal ganglia contained two main frequencies: a high beta (around 26 Hz), and a low beta (around 18 Hz). The high beta (around 26 Hz) power decreased in the STN and GPi, whereas the low beta (around 18 Hz) power decrease was consistently found only in the GPi. Both frequencies changed their power with a specific temporal modulation related to the different movement phases. L-DOPA specifically and selectively influenced the spectral power changes in these two signal bands.

Comparison of pharmacological treatment versus acupuncture treatment for migraine without aura--analysis of socio-medical parameters.

This study was carried out in 120 patients affected by migraine without aura, treated in 4 public health centers and randomly divided into acupuncture group (AG) and conventional drug therapy group (CDTG). The evaluation of clinical results was made 6 and 12 months after the beginning of treatment and was worked out as well according to socio-medical parameters. Acupuncture was applied to the following points: Touwei (ST 8), Xuanlu (GB 5), Fengchi (GB 20), Dazhui (GV 14), Lieque (LU 7), treated with the reducing method. In AG, the figure scoring the entity and frequency of migraine attacks drops from 9,823 before treatment to 1,990 6 months after and 1,590 12 months after; while in CDTG, it drops from 8,405 before treatment to 3,927 6 months after and 3,084 12 months after. In AG, the total absence from work amounted to 1,120 working days/year, with a total cost (private + social costs) of 186,677,000 Italian liras. In CDTG, the absence from work amounted to 1,404 working days/year, with a total cost of 266,614,000 Italian liras. If we consider that in Italy the patients affected by migraine without aura are around 800,000, and that acupuncture therapy is able to save 1,332,000 Italian liras on the total average cost supported for every single patient, the application of acupuncture in the treatment of migraine without aura would allow a saving of the health expenses in Italy of over 1,000 billion liras.