The role of skin tests with polyethylene glycol and polysorbate 80 in the vaccination campaign for COVID-19: results from an Italian multicenter survey.

Summary: Background. International guidelines suggested skin tests with Polyethylene-glycol (PEG) and polysorbate 80 (PS-80), to investigate a possible hypersensitivity to these excipients either to identify subjects at risk of developing allergic reactions to Covid-19 vaccines, or in patients with suspected IgE mediated hypersensitivity reactions (HR) to the Covid-19 vaccine. The main purpose of this study was to investigate the prevalence of PEG and PS sensitization in patients with a clinical history of HR to drugs containing PEG/PS and in patients with a suspected Covid-19 vaccine immediate HR. Methods. This was a multicenter retrospective study conducted by allergists belonging to 20 Italian medical centers. Skin testing was performed in 531 patients with either a clinical history of suspected hypersensitivity reaction (HR) to drugs containing PEG and/or PS-80 (group 1:362 patient) or a suspected HR to Covid-19 vaccines (group 2: 169 patient), as suggested by the AAIITO/SIAAIC guidelines for the "management of patients at risk of allergic reactions to Covid-19 vaccines" [1]. Results. 10/362 (0.02%) had positive skin test to one or both excipients in group 1, 12/169 (7.1%) in group 2 (p less than 0.01). In group 2 HRs to Covid-19 vaccines were immediate in 10/12 of cases and anaphylaxis occurred in 4/12 of patients. Conclusions. The positivity of skin test with PEG and or PS before vaccination is extremely rare and mostly replaceable by an accurate clinical history. Sensitization to PEG and PS has to be investigated in patients with a previous immediate HR to a Covid-19 vaccine, in particular in patients with anaphylaxis.

Early social isolation differentially affects the glucocorticoid receptor system and alcohol-seeking behavior in male and female Marchigian Sardinian alcohol-preferring rats.

Adverse early life experiences during postnatal development can evoke long-lasting neurobiological changes in stress systems, thereby affecting subsequent behaviors including propensity to develop alcohol use disorder. Here, we exposed genetically selected male and female Marchigian Sardinian alcohol-preferring (msP) and Wistar rats to mild, repeated social deprivation from postnatal day 14 (PND14) to PND21 and investigated the effect of the early social isolation (ESI) on the glucocorticoid receptor (GR) system and on the propensity to drink and seek alcohol in adulthood. We found that ESI resulted in higher levels of GR gene and protein expression in the prefrontal cortex (PFC) in male but not female msP rats. In female Wistars, ESI resulted in significant downregulation of Nr3c1 mRNA levels and lower GR protein levels. In male and female msP rats, plasma corticosterone levels on PND35 were similar and unaffected by ESI. Wistar females exhibited higher levels of corticosterone compared with males, independently from ESI. In alcohol self-administration experiments we found that the pharmacological stressor yohimbine (0.0, 0.312, 0.625, and 1.25 mg/kg) increased alcohol self-administration in both rat lines, regardless of ESI. After extinction, 0.625 mg/kg yohimbine significantly reinstated alcohol seeking in female rats only. ESI enhanced reinstatement in female msP rats. Overall, the present results indicate that repeated social deprivation during the third week of postnatal life affects GR expression in a strain- and sex-dependent manner: such effect may contribute, at least partially, to the heightened sensitivity of female msP rats to the effects of yohimbine-induced alcohol seeking.

Review: Pig-based bioconversion: the use of former food products to keep nutrients in the food chain.

The primary challenge of agriculture and livestock production is to face the growing competition between food, feed, fibre, and fuel, converting them from resource-intensive to resource-efficient. A circular economy approach, using agricultural by-products/co-products, in the livestock production system would allow to reduce, reuse, and redistribute the resources. Former food products (FFPs), also named ex-foods, could represent a valid option in strengthening resilience in animal nutrition. FFPs have a promising potential to be included regularly in animal diets due to their nutritive value, although their potential in animal nutrition remains understudied. A thorough investigation of the compositional and dietary features, thus, is essential to provide new and fundamental insights to effectively reuse FFPs as upgraded products for swine nutrition. Safety aspects, such as the microbial load or the presence of packaging remnants, should be considered with caution. Here, with a holistic approach, we review several aspects of FFPs and their use as feed ingredients: the nutritional and functional evaluation, the impact of the inclusion of FFPs in pigs' diet on growth performance and welfare, and further aspects related to safety and sustainability of FFPs.

Vespa velutina nigrithorax venom allergy: inhibition studies approach for the choice of specific immunotherapy.

Summary: Vespa velutina nigrithorax (VVN), commonly known as Asian wasp because endemic in Asia, represents an alien species in Europe. VVN can induce allergic reactions similar to those caused by other Hymenoptera and death after VVN stings, presumably due to fatal allergic reactions, has been reported. In the treatment of Hymenoptera venom hypersensitivity, specific immunotherapy (VIT) is highly effective. Currently, there is no specific available VIT for VVN, so it is relevant to assess if patients stung by VVN and showing allergic reactions could be treated with the Hymenoptera commercially available extracts Vespa crabro (VC) and Vespula spp (Vspp) or if they need the specific VIT with VVN venom extract. Methods. Four patients with a clinical history of systemic reactions after VVN sting were evaluated. Serum specific IgE were assayed quantitatively with an automated fluoro-enzyme immunoassay ImmunoCAP™ Specific IgE by Phadia™ 1000 System (Thermo Fisher Scientific, Uppsala, Sweden) for VC, Vspp and VVN. Cap inhibition assays were performed incubating serum samples with 200 µl of each venom at increasing concentrations and subsequently specific IgE against each of the venoms were determined in the samples by Phadia™ 250 System (Thermo Fisher Scientific, Uppsala, Sweden). Results. Our results suggested that both Vspp and VC venoms were able to inhibit the specific IgE for VVN, although the VC compared to the Vspp venom showed a higher inhibition. Conclusions. Our inhibition studies suggested that VIT with VC venom, nowadays when there is not specific available VIT for VVN, may be more effective than Vspp VIT in patients with VVN sting reactions.

Sugary vs salty food industry leftovers in postweaning piglets: effects on gut microbiota and intestinal volatile fatty acid production.

Awareness of the need to improve the sustainability of livestock by reducing the loss of natural resources has increased significantly. This study investigated the effects of two categories of food industry leftovers, also referred to as former foodstuff products (FFPs), on pig gut microbiota and intestinal volatile fatty acid (VFA) production. Thirty-six female postweaning piglets (28 days old, Large White × Landrace, 6.5 ±â€¯1.1 kg) were separated into three groups and fed a conventional diet (CTR), and diets in which cereals were partially replaced (30% w/w) by sugary confectionery products (FFPs-C) or salty bakery products (FFPs-B), respectively. After 42 days of dietary treatments, faeces were collected from the rectal ampulla, snap-frozen, and used for next-generation sequencing to analyse the composition and the alpha and beta diversity indexes of the microbial population. The concentration of VFAs in the intestinal content collected at the slaughterhouse was also analysed. The study demonstrated that balanced diets can be obtained by the inclusion of both FFPs-C and FFPs-B, with a similar chemical composition compared to traditional diets. Neither the FFPs-C nor FFPs-B diets affected the abundance and biodiversity indexes of the microbial community. Only a few taxa, normally attributed to a healthy gut, increased with FFPs-C and FFPs-B compared to the CTR. The experimental diets had no impact on the production of the VFAs in the faeces. Lastly, the inclusion at 30% (w/w) of both categories of FFP diets slightly affected the faecal microbiota. FFPs could thus be used as a promising alternative to traditional ingredients in pig diets; however, additional analyses are needed to further investigate the presence of potentially pathogenic bacteria. The effects of such ingredients on other markers of gut health, and on product quality when used in the fattening period also need to be investigated.

Delayed corticosteroid hypersensitivity: a clinical management proposal.

Summary: Background. Different clinical pictures are related to corticosteroids (CS) non immediate hypersensitivity and the frequency of these reactions can be underestimated. The classification of CS in 3 groups and the identification of two patient's profiles has been proposed by Baeck to help clinicians in the management of these cases. Methods. Data of 14 patients with clinical history of delayed reactions to various CS and positive skin test and/or oral challenge are retrospectively analyzed. Results. Three different patterns of patients are identified evaluating history, clinical picture and tests results. The first one (6 pts, 43%) is characterized by cutaneous and/or mucosal reaction due to inhaled Budesonide and patch test positive only to topical molecules belonging to the group 1 of CS. The second pattern (4 pts) has clinical history of local and systemic skin reactions to the topic and parenteral administration of the same or other steroid drugs. Patients belonging to the third pattern (4 pts) have a history of systemic reactions to general administration of CS without previous contact reaction. Pattern 2 and 3 show a wide sensitization to molecules belonging to the 3 groups of CS. All the patients show patch test positive to Budesonide. Conclusions. Although the lack of standardization, the allergy workup proves useful to differentiate patients sensitized to one or few molecules from polysensitized and to identify the culprit drugs. Intradermal and challenge test are necessary to complete the diagnostic workup. The results suggest the possibility of a different management of patients. Patients of pattern one can be only patch tested with a limited series of CS belonging to the 3 groups. They don't need an extensive exclusion of steroids use. The pattern 2 and 3 must be submitted instead to a complete allergological individual evaluation to identify alternative tolerated drugs, because of the risk of systemic reactions. The Baeck's classification shows limited usefulness in these cases.

Structure-activity relationships and mechanism of action of tetragomycin derivatives as inhibitors of Staphylococcus aureus staphyloxanthin biosynthesis.

Despite the main strategy to overcome bacterial resistance has focused on the development of more potent antimicrobial agents, the evolutionary pressure caused by such drugs makes this strategy limited. Molecules that interfere with virulence factors appear as a promising alternative though, as they cause reduced selective pressure. As a matter of fact, staphyloxanthin biosynthesis inhibition (STXBI) has been pursued as promising strategy to reduce S. aureus virulence. Herein, we report the inhibitory profile of 27 tetrangomycin derivatives over staphyloxanthin production. The experimental result showed that naphthoquinone dehydro-α-lapachone (25 - EC50 = 57.29 ± 1.15 µM) and 2-Isopropylnaphtho[2,3-b]furan-4,9-dione (26 EC50 = 82.10 ± 1.09 µM) are the most potent compounds and suggest that hydrogen acceptor groups and lipophilic moieties decorating the naphthoquinone ring are crucial for STXBI. In addition, we present an in situ analysis, through RAMAN spectroscopy, that is inexpensive and might be employed to probe the mechanism of action of staphyloxanthin biosynthesis inhibitors. Therefore, our molecular simplification strategies afforded promising lead compounds for the development of drugs that modulate S. aureus staphyloxanthin biosynthesis.

LSD1 is an environmental stress-sensitive negative modulator of the glutamatergic synapse.

Along with neuronal mechanisms devoted to memory consolidation -including long term potentiation of synaptic strength as prominent electrophysiological correlate, and inherent dendritic spines stabilization as structural counterpart- negative control of memory formation and synaptic plasticity has been described at the molecular and behavioral level. Within this work, we report a role for the epigenetic corepressor Lysine Specific Demethylase 1 (LSD1) as a negative neuroplastic factor whose stress-enhanced activity may participate in coping with adverse experiences. Constitutively increasing LSD1 activity via knocking out its dominant negative splicing isoform neuroLSD1 (neuroLSD1KO mice), we observed extensive structural, functional and behavioral signs of excitatory decay, including disrupted memory consolidation. A similar LSD1 increase, obtained with acute antisense oligonucleotide-mediated neuroLSD1 splicing knock down in primary neuronal cultures, dampens spontaneous glutamatergic transmission, reducing mEPSCs. Remarkably, LSD1 physiological increase occurs in response to psychosocial stress-induced glutamatergic signaling. Since this mechanism entails neuroLSD1 splicing downregulation, we conclude that LSD1/neuroLSD1 ratio modulation in the hippocampus is instrumental to a negative homeostatic feedback, restraining glutamatergic neuroplasticity in response to glutamate. The active process of forgetting provides memories with salience. With our work, we propose that softening memory traces of adversities could further represent a stress-coping process in which LSD1/neuroLSD1 ratio modulation may help preserving healthy emotional references.

Abnormalities of acid-base balance and predisposition to metabolic acidosis in Metachromatic Leukodystrophy patients.

Metachromatic Leukodystrophy (MLD; MIM# 250100) is a rare inherited lysosomal storage disorder caused by the deficiency of Arylsulfatase A (ARSA). The enzymatic defect results in the accumulation of the ARSA substrate that is particularly relevant in myelin forming cells and leads to progressive dysmyelination and dysfunction of the central and peripheral nervous system. Sulfatide accumulation has also been reported in various visceral organs, although little is known about the potential clinical consequences of such accumulation. Different forms of MLD-associated gallbladder disease have been described, and there is one reported case of an MLD patient presenting with functional consequences of sulfatide accumulation in the kidney. Here we describe a wide cohort of MLD patients in whom a tendency to sub-clinical metabolic acidosis was observed. Furthermore in some of them we report episodes of metabolic acidosis of different grades of severity developed in acute clinical conditions of various origin. Importantly, we finally show how a careful acid-base balance monitoring and prompt correction of imbalances might prevent severe consequences of acidosis.

Vocalizations during electroejaculation in anaesthetized adult and young pampas deer (Ozotoceros bezoarticus) males.

The aim of this study was to characterize the vocalizations produced during electroejaculation under general anaesthesia in pampas deer males and to determine whether the characteristics of those vocalizations differ in adult and young pampas deer males. Electroejaculation was applied to 13 adults (AM) and 13 young (YM) males under general anaesthesia. Vocalizations were digitally recorded, and the number and duration of vocalizations, the latency in relation to each voltage, the total time vocalizing, and the structure of the fundamental frequency (F0) [initial frequency (F(start)), maximal frequency (F(max)), minimal frequency (F(min)) and final frequency (F(end))] were analysed. No male vocalized with 0 V; the number of animals that vocalized increased at 2 and 3 V and increased again at 4, 5 and 6 V (p < 0.05). The latency time from the beginning of each series (each voltage) decreased until 4 V (p < 0.01). The number of vocalizations/voltage increased from 4 V (p < 0.05). The length of each vocalization and the total time during which animals vocalized were greater in YM than AM (p = 0.02 and p = 0.01, respectively). Similarly, the fundamental frequencies were higher in YM than AM (p ≤ 0.05). Overall, we concluded that the vocalizations emitted during electroejaculation in pampas deer under general anaesthesia are related to the voltage applied during the process. Young males vocalize more time, probably due to a greater sensibility to the electric stimulation. The differences in the characteristics of the vocalizations between adult and young males may be related to the anatomic differences in the neck of adult or young males.

Tumor suppressor Nf2/merlin drives Schwann cell changes following electromagnetic field exposure through Hippo-dependent mechanisms.

Previous evidence showed mutations of the neurofibromin type 2 gene (Nf2), encoding the tumor suppressor protein merlin, in sporadic and vestibular schwannomas affecting Schwann cells (SCs). Accordingly, efforts have been addressed to identify possible factors, even environmental, that may regulate neurofibromas growth. In this context, we investigated the exposure of SC to an electromagnetic field (EMF), which is an environmental issue modulating biological processes. Here, we show that SC exposed to 50 Hz EMFs changes their morphology, proliferation, migration and myelinating capability. In these cells, merlin is downregulated, leading to activation of two intracellular signaling pathways, ERK/AKT and Hippo. Interestingly, SC changes their phenotype toward a proliferative/migrating state, which in principle may be pathologically relevant for schwannoma development.

Sperm characterization and identification of sperm sub-populations in ejaculates from pampas deer (Ozotoceros bezoarticus).

Pampas deer (Ozotoceros bezoarticus) is a native endangered species. Knowledge of the basic spermiogram characteristics and the morphometric descriptors is necessary to effectively develop sperm cryopreservation. In other species, sperm sub-population is related to sperm cryo-resistance. The objective was to provide a general description of the sperm, including sperm head morphometric descriptors, its repeatability, and the existence of sperm sub-populations. Sperm were obtained from adult males by electroejaculation during the breeding season. The motility score was 3.4 ± 0.2 (mean ± SEM) and progressive motility was 59.4 ± 3.7%. Ejaculated volume was 413.9 ± 51.0 µl, the total number of sperm ejaculated was 321.2 ± 55.4 × 10(6). Also, 63.3 ± 3.1% of the sperm were morphologically abnormal and 23.7 ± 2.3% had acrosome damage. The sperm head length was 7.6 ± 0.01 µm, width 4.4 ± 0.01 µm, area 28.1 ± 0.07 µm(2) and the perimeter was 21.9 ± 0.04 µm. There was a positive relationship among morphometric descriptors and the motility score, overall motility and progressive motility. Also length (P=0.011), width (P=0.003), area (P=0.006) and perimeter (P=0.009) of sperm head obtained in two different collections were positively related. Overall, the low concentration, volume, overall quality and abnormal morphology, and wide variation of these variables may be a limitation for the development of sperm cryopreserved banks. There were three sperm sub-populations with different morphometric characteristics. The morphometric descriptors are maintained similarly among different collections.

Illness perception, mood and coping strategies in allergic rhinitis: are there differences among ARIA classes of severity?

BACKGROUND: This study was designed to assess if illness perception, mood state and coping strategies differ according to allergic rhinitis (AR) persistence and severity. METHODS: Illness perception, mood profiles, coping behaviors and rhinitis symptoms were assessed by means of validated tools inpatients classified according to the Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines. RESULTS: Two hundred and thirty-one patients underwent data analysis. No difference in age, sex, socio-economic status, smoking habits was detected comparing patients according to AR severity, duration or 4 ARIA classes. Patients with intermittent AR reported higher scores than those with persistent AR in confusion-bewilderment of Profile of Mood States (POMS); patients with moderate/severe rhinitis had significantly higher scores than those with mild rhinitis in TSSS, Identity and Consequences. No differences were detected in all assessed outcomes in the 4 ARIA classes. CONCLUSIONS: The patient's perspective about AR is independent of persistence and severity of symptoms. This may explain why AR remains under-diagnosed and under-treated, even in its most severe forms. Self-management plans should consider the patient's perspective.

Modulation of neuronal plasticity following chronic concomitant administration of the novel antipsychotic lurasidone with the mood stabilizer valproic acid.

RATIONALE: Combinatory therapy is widely used in psychiatry owing to the possibility that drugs with different mechanisms of action may synergize to improve functions deteriorated in schizophrenia, bipolar disorders, and major depression. While combinatory strategies rely on receptor and synaptic mechanisms, it should also be considered that two drugs may also "interact" on the long-term to determine more robust changes in neuronal plasticity, which represents a downstream target important for functional recovery. OBJECTIVE: The aim of the study is to investigate neuroadaptive changes set in motion by chronic concomitant administration of the novel antipsychotic lurasidone and the mood stabilizer valproate. METHODS: Animals were chronically treated with lurasidone, valproate, or the combination of the two drugs and killed 24 h after the last injection to evaluate alterations of different measures of neuronal plasticity such as the neurotrophin brain-derived neurotrophic factor (BDNF), the immediate early gene Activity-regulated cytoskeletal associated protein, and the epigenetic regulators HDAC 1, 2, and 5 in dorsal and ventral hippocampus. RESULTS: The results suggest that coadministration of lurasidone and valproate produces, when compared to the single drugs, a larger increase in the expression of BDNF in the ventral hippocampus, through the regulation of specific neurotrophin transcripts. We also found that the histone deacetylases were regulated by the drug combination, suggesting that some of the transcriptional changes may be sustained by epigenetic mechanisms. CONCLUSIONS: Our results suggest that the beneficial effects associated with combinatory treatment between a second-generation antipsychotic and a mood stabilizer could result from the ability to modulate neuroplastic molecules, whose expression and function is deteriorated in different psychiatric conditions.

Montelukast effects on inflammation in allergic rhinitis: a double blind placebo controlled pilot study.

It has been demonstrated that Leukotriene modifiers reduce rhinitis symptoms, but montelukast preventive effect on inflammatory cells pattern in intranasal challenge studies has not been already assessed. This pilot study has been designed to explore the montelukast effects in preventing early/late inflammatory cells response to specific allergen challenge in persistent rhinitis. After a 4 week wash-out period, patients were randomised to receive montelukast/placebo for 4 weeks. Pre-post treatment nasal washing and scraping before and after specific nasal challenge were performed. No difference in baseline inflammatory cells count before and after treatment was shown between groups. Despite at a basal level a decrease of inflammatory cells in active group after treatment was observed, the statistical significance was not reached. The generalised mixed model showed that, after therapeutic interventions, the inflammatory cells increased 30' and 6 hour after challenge but, only in the active group the cells amounting was less for eosinophils (-34%), macrophages (-56%), lymphocytes (-45%) and neutrophils (-46%; p = 0.001). The longitudinal generalised linear model with just one time variable showed a decrease of all inflammatory cellular types although a significant relevance was reached only for macrophages (p = 0.038) and neutrophils (p = 0.001). The modulatory effect on neutrophils and macrophages could lead to montelukast still unexplored effects. Specific trials, sized according to the results of this pilot exploratory study, could add relevant evidences concerning the leukotrienes receptors antagonist treatment of specific rhinitis and asthma phenotypes.

The pulmonary pharmacology of [4-methoxy-N1-(4-trans-nitrooxycyclohexyl)-N3-(3-pyridinylmethyl)-1,3-benzenedicarboxamide] (2NTX-99), an anti-atherotrombotic compound with therapeutic potential in pathological conditions that target lung vasculature.

The pharmacological activity of 2NTX-99 ([4-methoxy-N1-(4-trans-nitrooxycyclohexyl)-N3-(3-pyridinylmethyl)-1,3-benzenedicarboxamide]) was investigated in vitro in the intact, rat pulmonary vasculature and in guinea pig airways. Rat lungs were perfused at constant flow and changes in vascular tone recorded. Challenge with the TXA2 analogue 9,11-dideoxy-9α11α-methanoepoxy ProstaglandinF2 (U46619, 0.5 µM) increased vessel tone (32.48±1.5 vs 13.13±0.56 mmHg; n=12). 2NTX-99 (0.1-100 µM; n=5), caused a concentration-dependent relaxation, prevented by 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 10 µM, n=4), an inhibitor of soluble guanylate cyclase. Acetylcholine (0.1-10 µM; n=3) and a reference NO-donor, isosorbide-5-mononitrate (5-100 µM; n=4), were ineffective. Intraluminal perfusion of washed human platelets (2 × 108 cells/ml) increased intravascular pressure after challenge with arachidonic acid (AA, 2 µM; n=5), an increase abolished by acetylsalicylic acid and significantly reduced by 2NTX-99 (40 µM; n=5). TXB2 in the lung perfusate was detected after platelet activation, 2NTX-99 inhibited TXA2 synthesis (6.45±0.6 and 1.10±0.2 ng/ml, respectively). 2NTX-99 did not alter central or peripheral airway responsiveness to Histamine (0.001-300 µM; n=6), U46619 (0.001-3 µM, n=3) or LTD4 (1 pM-1 µM; n=6). 2NTX-99 vasodilates the pulmonary vasculature via the release of nitric oxide (NO) and reduces intraluminal, AA-induced, TXA2 formation. The combined activity of 2NTX-99 as an NO-donor and a TXA2-synthesis inhibitor provides strong support for its potential therapeutic use in pathologies of the pulmonary vascular bed (e.g. pulmonary hypertension).

Physiological and biochemical parameters in response to electroejaculation in adult and yearling anesthetized pampas deer (Ozotoceros bezoarticus) males.

The aim of this study was to characterize changes in physiological and biochemical parameters during electroejaculation (EE) under general anaesthesia in adult and yearling pampas deer males (Ozotoceros bezoarticus). The relation between heart rate, pulse rate, respiratory rate and oximetry with EE voltages was studied. The changes in cortisol, alkaline phosphatase, creatine kinase, aspartate aminotransferase and rectal temperature were determined before and after electroejaculation (BEE and AEE). Heart rate and pulse rate values increased during EE, with a greater increase in heart rate in adults (p < 0.01). Respiratory rate and SpO(2) were not affected by EE or category. The rectal temperature decreased in adults and yearlings during EE (p = 0.0001). Alkaline phosphatase, creatine kinase and aspartate aminotransferase concentrations increased AEE (p < 0.001, p < 0.01 and p < 0.05, respectively). Alkaline phosphatase and creatine kinase concentrations were greater in young than in adult males (p < 0.05). In conclusion, the EE under general anaesthesia in the pampas deer provoked increases in heart and pulse rates, as well as in creatine kinase, aspartate aminotransferase and alkaline phosphatase concentrations, and a decrease in rectal temperature in both categories. Oximetry values were especially low during the procedure. Heart rate increase was greater in adult males, and alkaline phosphatase and creatine kinase concentrations were greater in yearlings.

GAPP Italy: "A survey on asthma on Italian physicians and patients".

Guidelines recognize the importance of achieving and maintaining asthma control: the treatment strategies nw available allow the control of the great majority of patients with asthma but despite many efforts only 5% of patients achieve guideline-defined asthma control. The GAPP (The Global Asthma Physician and Patient survey) is a global quantitative survey with the aiim of identifying barriers to optimal management of asthma. Physicians and adult patients with persistent asthma have been interviewed with closed-ended questions questionnaire. This study has been conducted in 16 countries. In Italy the survey has revealed that physicians prescribe a combination of ICS and LABA more often in the other countries. They consider ICS the first-line treatment for mild persistent asthma. They are not completely satified with ICS because of local and systemic side effects. At the same time, the reason why patients change asthma medication is the potential for side effects. The two group responses were found to differ about the time spent discussing how to improve the management of asthma. A better communication between physician and patient and a new treatment option with lower side effect profile could be the key point to achieve asthma control in a larger number of patients.

Acute spinal cord injury reduces brain derived neurotrohic factor expression in rat hippocampus.

Spinal cord injury (SCI) is a devastating event which causes dramatic changes in the everyday life of the patient. We have found that acute SCI reduced BDNF expression selectively in the hippocampus of lesioned rats, a decrease which persists at least 1 week, thus identifying the modulation of the neurotrophin biosynthesis as an important mechanism underlying brain vulnerability to SCI. These data are the first to show that SCI alters hippocampal BDNF expression and identify the neurotrophin as a potential target through which SCI changes brain functions, a notion that might prove useful in understanding the mechanisms underlying brain vulnerability to SCI.