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L’aumento dell’antibiotico resistenza dei microrganismi patogeni è sempre più evidente e drammatico: in questo scenario lo studio dell’attività antimicrobica degli oli essenziali (OE) è di grande rilievo per la possibilità di individuare nuove strategie a supporto delle terapie antimicrobiche. L’impiego degli OE in medicina, veterinaria, industria alimentare e agricoltura non ha evidenziato, infatti, la presenza di geni di resistenza nei microrganismi bersaglio: i patogeni non riescono a sviluppare resistenza verso i molteplici meccanismi molecolari messi in atto dai numerosi componenti bioattivi con attività sinergica presenti negli OE. La ricerca di nuovi OE, inoltre, può contribuire ad individuare molecole antimicrobiche attive per diversi scopi applicativi. Scopo. La presente attività di ricerca ha riguardato lo studio dell’attività antimicrobica di OE ed idrolati di Monarda fistulosa e M. didyma, appartenenti alla famiglia delle Lamiaceae, che grazie all’elevata presenza di timolo possono rivelarsi molto promettenti contro microrganismi patogeni. In particolare sono stati messi a confronto gli OE derivati da piante coltivate in due anni consecutivi al fine di evidenziare possibili differenze di attività antimicrobica. Materiali e Metodi. Gli OE M. fistulosa e M. didyma sono stati ottenuti da coltivazioni delle relative piante officinali presso l’ITAS Ghini-Scarabelli di Imola e “Il Giardino delle Erbe” di Casola Valsenio (Ravenna). I microrganismi saggiati sono stati sia lieviti (Candida albicans ATCC 48274, Candida pseudointermedia CBS 6918, Candida stellata CBS 943, Candida tropicalis CBS 94, Candida utilis CBS 621), sia batteri patogeni per l’uomo e gli animali (Enterococcus faecalis, Escherichia coli M12, Staphylococcus aureus), sia batteri benefici (Bifidobacterium animalis spp. lactis MB29, Bifidobacterium animalis spp. animalis T6). La MIC (Minimal Inhibitory Concentration) è stata valutata utilizzando il metodo validato secondo CLSI. Brevemente, i microrganismi sono stati coltivati nel substrato idoneo (YPD per i lieviti, Nutrient Broth per i patogeni e MRS addizionato di cisteina 0.05% per i bifidobatteri) ed incubati nelle condizioni appropriate (30°C per i lieviti e 37°C per tutti gli altri). Per quanto riguarda gli OE, è stato utilizzato il tween 80 (0.001%) come emulsionante per aumentarne la solubilità e sono state saggiate le concentrazioni da 0.0078 a 4%. Per quanto riguarda gli idrolati sono state saggiate le diluizioni 1:2, 1:4 e 1:8. Sono state inoculate 105 cellule per pozzetto in piastre multiwell da 96 pozzetti e la crescita microbica è stata valutata a 24 e 48 ore mediante lettura spettrofotometrica a 600 nm. La MLC (Minimal Lethal Concentration) è stata misurata inoculando in piastra 10μl prelevati dai 3 pozzetti adiacenti al pozzetto dove si osservava la crescita e incubando alle condizioni adatte ai vari microrganismi saggiati. Risultati. Nonostante la composizione degli OE sia diversa fra le due specie di Monarda e fra i diversi anni di coltivazione, gli OE hanno mostrato una simile attività antimicrobica verso i lieviti e i batteri saggiati. In generale, gli OE testati hanno rivelato bassi valori di MIC, cioè una più forte attività antimicrobica, verso i microrganismi patogeni come E. coli e C. albicans, rispetto alle MIC attive verso i microrganismi benefici come i bifidobatteri. Gli idrolati di Monarda mostrano anch’essi attività antimicrobica paragonabile a quella degli OE: gli idrolati, essendo già in un mezzo acquoso, potrebbero avere una maggiore facilità di impiego non richiedendo emulsionanti. Conclusioni: La maggiore sensibilità dei microrganismi patogeni supporta un potenziale utilizzo degli OE di Monarda come agenti antimicrobici grazie al loro vantaggioso profilo di selettività. Possibili applicazioni potrebbero essere in campo medicoveterinario, alimentare e agronomico. Tuttavia saranno necessari studi in vivo per confermare i dati ottenuti in vitro.

De acuerdo con la concepción ortodoxa (y supuestamente cartesiana), la indiscernibilidad entre sueño y sensación legitima un escepticismo extremo que desvincula nuestras experiencias de sus nexos causales y de sus fundamentos epistémicos. Ernest Sosa le opone un modelo imaginativo: mientras soñamos nuestro proceso cognitivo se encuentra desactivado. Ello implicaría, entre otras cosas: (i) atribuir al sujeto dos sistemas contradictorios de creencias; (ii) exigirle responsabilidad moral por lo que decide en sueños; y (iii) extender el escepticismo hasta el propio hecho de que se juzga y se piensa. Nos proponemos mostrar: (i) cómo el modelo de Descartes ni es identificable con la concepción ortodoxa ni se encuentra lógicamente alejado del modelo imaginativo; (ii) cómo permite detectar en la extensión sosiana del cogito una falacia por equivocación; (iii) finalmente, cómo permite salvaguardar la solidez del cogito, evitando al mismo tiempo comprometerse con una ontología fenomenista y con la recusación del escepticismo perceptivo.

L’efficacia antimicrobica degli oli essenziali (OE) nei confronti di patogeni vegetali attraverso la diretta somministrazione alle piante, specie se asintomatiche, in modo da contrastare la crescita di batteri endofiti, offre un’opportunità da non sottovalutare nella lotta alle batteriosi, settore in cui (prodotti rameici ad azione preventiva esclusi) non sono ancora disponibili agrofarmaci in grado di debellare una malattia in atto. L’attenzione verso batteri fitopatogeni da quarantena che in Italia negli ultimi anni hanno comportato ingenti perdite economiche, hanno indotto a valutare l’effetto antimicrobico in vitro di OE ottenuti da Monarda didyma e M. fistulosa nei confronti di Pseudomonas syringae pv. actinidiae (Psa) ed Erwinia amylovora (Ea). Nel cancro batterico dell’actinidia causato da Psa tutti gli organi vegetativi della pianta vengono seriamente compromessi con cali di resa e gravi ripercussioni economiche specialmente se si considera che l’Italia rappresenta il primo produttore di kiwi nell’emisfero Nord (Cina esclusa) contribuendo al 70% della produzione globale. Per contrastare la diffusione di questa malattia sono essenziali misure di controllo da applicare tempestivamente dato che attualmente sono disponibili solo interventi preventivi. Il colpo di fuoco batterico causato da Ea infetta piante di grande importanza economica quali pero e melo: la malattia si manifesta con avvizzimenti fiorali e fogliari, necrosi di frutticini e cancri corticali in rami, branche e fusto. In Italia la malattia è comparsa nel 1990 in Puglia, nel 1994 in Emilia-Romagna e si è poi diffusa in tutta la pianura Padana. In base a studi precedenti sull’effetto di timolo e carvacrolo sulla crescita di Ea in vitro è stata evidenziata una completa inibizione a 50 mM in piastre di agar a doppio strato e a 35 mM con il metodo di diffusione su dischetto. Dato che negli OE di Monarda spp. il timolo rappresenta uno dei componenti principali, è stata saggiata la loro attività nei confronti di Psa ed Ea. L’OE estratto nel 2003 da M. fistulosa è stato usato come olio di riferimento, mentre gli OE estratti negli anni 2010, 2011 e 2012 da M. didyma e da M. fistulosa sono stati usati in diverse concentrazioni ottenendo risultati incoraggianti. In particolare è stata evidenziata una maggiore efficacia antimicrobica per l’OE estratto da M. fistulosa nel 2012 nei confronti di Psa e in misura inferiore contro Ea. La diversa attività antimicrobica degli OE usati in questo studio preliminare nei confronti dei due batteri fitopatogeni è stata correlata con la loro diversa composizione chimica.

OBJECTIVE: Recent findings support greater efficacy of early vs. delayed interferon beta (IFNbeta) treatment in patients with a first clinical event suggestive of multiple sclerosis (MS). We aimed to evaluate the effectiveness of early IFNbeta treatment in definite relapsing-remitting MS (RRMS) and to assess the optimal time to initiate IFNbeta treatment with regard to the greatest benefits on disability progression. METHODS: A cohort of 2,570 IFNbeta-treated RRMS patients was prospectively followed for up to 7 years in 15 Italian MS Centers. A Cox proportional hazards regression model adjusted for propensity score (PS) quintiles was used to assess differences between groups of patients with early vs. delayed IFNbeta treatment on risk of reaching a 1-point progression in the Expanded Disability Status Scale (EDSS) score, and the EDSS 4.0 and 6.0 milestones. A set of PS-adjusted Cox hazards regression models were calculated according to different times of treatment initiation (within 1 year up to within 5 years from disease onset). A sensitivity analysis was performed to assess the robustness of findings. RESULTS: The lowest hazard ratios (HRs) for the three PS quintiles-adjusted models were obtained by a cutoff of treatment initiation within 1 year from disease onset. Early treatment significantly reduced the risk of reaching a 1-point progression in EDSS score (HR = 0.63; 95% CI = 0.48-0.85; p < 0.002), and the EDSS 4.0 milestone (HR = 0.56; 95% CI = 0.36-0.90; p = 0.015). Sensitivity analysis showed the bound of significance for unmeasured confounders. INTERPRETATION: Greater benefits on disability progression may be obtained by an early IFNbeta treatment in RRMS.

The balance and the composition of the intestinal microbiota are important for the well-being and the ability of our bodies to resist to the invasion of phatogens. Many causes can alter this delicate balance, but the ingestion of antimicrobial agents is the most important. Then, to help the bowel and to increase the natural resistance of the host to infection, probiotic microorganisms such as lactobacilli and bifidobacteria can be consumed. The safety of these probiotic strains is essential, particularly that they should not be able to transfer to other bacteria any possible resistance to antimicrobial agents. Antibiotic resistance is an emerging issue nowadays. We have studied the antibiotic resistance of some probiotic microorganisms, for two reasons: to verify their ability to survive if taken at the same time as antibiotic therapy, and to increase the selective properties of media used for their isolation from samples containing mixed bacterial populations. We have isolated from commercial dairy and pharmaceutical products, 34 strains declared as probiotics, belonging to the genera Bifidobacterium [1] and Lactobacillus [2], and 21 strains of starter culture bacteria. All the microorganisms were identified using electrophoresis of the soluble proteins. The bifidobacteria were Bifidobacterium animalis except for one Bifidobacterium longum. Sometimes the identification showed that the strain found was not the one indicated on the label. The lactobacilli were L. acidophilus, L. casei, and Lactobacillus delbrueckii subsp. bulgaricus. The minimum inhibitory concentration (MIC) of 24 common antibiotic substances was measured using the broth microdiluition method. All the isolated strains were sensitive to ampicillin, bacitracin, clindamycin, dicloxacillin, erytromycin, lincomycin, novobiocin, penicillin G, rifampicin, vancomycin (MIC90 ≤ 5 µg/ml). For chloramphenicol, cephalothin and tetracycline MIC90 was ≤ 50 µg/ml, while for cycloserine, kanamycin, metronidazole, gentamicin, nalidixic acid, polymyxin B, neomycin, paromomycin, aztreonam, spectinomycin, streptomycin, the MIC90 was ≥ 50 µg/ml.

The resistance to freezing at –135 °C and freeze-drying of potentially probiotic bifidobacteria strains isolated from human habitat and from commercial probiotic products already present in the Italian market were tested. The analysis was conducted in two different cryoprotectives, sucrose and skim milk. The strains of Bifidobacterium animalis, the only species found in the commercial probiotic product, were resistant to freezing and freeze-drying in both of the cryoprotectives used. Bifidobacteria from human habitat, B 1501 and B 632 Bifidobacterium breve strains and B 600/2, B 669/3 and B 2416 Bifidobacterium catenulatum strains, resulted as the most resistant strains in the storage processes in both cryoprotectives. These strains are potentially useful for industrial applications. In the strains tested the percentage of viable cells were higher after freezing than after freeze drying. The performance of the cryoprotectives analysed were strain-dependent.

This work presents preliminary data on the clinical utility and outcome predictors of The San Francisco Stop Smoking Internet Site (SFSSIS) (Lenert et al., 2003) used with weekly e-mail contacts and the usual pharmacological treatment. Fifty smokers participated in the current series of cases, 24 males and 26 females, with an age average of 43.24 (SD=10.24) years old. Thirty-two of the participants started the treatment. The abstinence rate in the post-treatment is 78.1% and in the one year follow-up 53.1%. The best outcome predictor in the post-treatment is the Beck Depression Inventory score (R2= 0.46, β= 0.51, p< 0.05), however in the one year follow-up the predictors are the carbon monoxide test (β1= 0.39, p< 0.05) and the age at time of starting to smoke (R2= 0.60, β2= 0.43, p< 0.05). It is important to emphasize that the participants were motivated to start the treatment and satisfied with it at the end. These preliminary results support the clinical utility of the SFSSIS for giving up smoking.

Background: Malignant pleural effusion is a clinical problem that impairs Quality of Life in patients with advanced malignancies. An indwelling pleural catheter is an alternative treatment to palliate some of the symptoms. Aim: To evaluate the Quality of Life of outpatients with malignant pleural effusion who were treated with an indwelling pleural catheter. Questionnaire compliance, catheter patency time, and survival were analyzed. Design: A multicenter observational study was conducted across five hospitals in Spain. Quality of Life was assessed at three different time points (before catheter placement and at 30 and 60 days post-placement) using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire QLQ-C30. For lung cancer patients, the QLQ-LC13 was also used. Participants: Patients with recurrent malignant pleural effusion treated with an indwelling pleural catheter. Results: A total of 51 outpatients completed the baseline QLQ-C30 questionnaire. Of these, 28 completed the questionnaire at 30 days. Of these 28 patients, 13 completed the questionnaire at 60 days. Scores showed a significant improvement in symptoms scales at 30 days (p = 0.03). Global health status and functional scales showed a non-significant trend to improvement at 30 and 60 days. A total of 27 lung cancer patients completed the QLQ-LC13 questionnaire. Items assessing dyspnea showed a significant improvement following catheter placement (p = 0.002). Conclusion: Indwelling pleural catheter is useful for palliative management of recurrent malignant pleural effusion in that it benefits Quality of Life in outpatients with advanced malignancies. In lung cancer patients, scores indicated that indwelling pleural catheter also provides significant relief of dyspnea.

10.1002/ajpa.22020

Las pretensiones del autor son: (i) Clarifi car la evolución del pensamiento de Wittgenstein siguiendo como hilo conductor su análisis de las fuentes y de los límites de lo normativo. (ii) Mostrar cómo el objetivo de Wittgenstein al construir modelos de lo normativo es evitar posiciones reduccionistas o naturalistas sin comprometerse por ello con marcos metafísicos, y cómo, por tanto, su análisis es especialmente relevante en el contexto contemporáneo, que afronta un aparente dilema entre constructivismo y realismo extremos. (iii) Situar el problema de la explicación de la necesidad en el contexto de la metodología terapéutica wittgensteiniana, demostrando que su enfoque es inteligible en relación a un método cuyo objetivo es la creación de modelos alternativos y la yuxtaposición de símiles con el objeto de quebrar la fascinación que una analogía única ejerce sobre nuestra inteligencia «Understanding necessity: the explanation of normativity in Wittgenstein». In this paper, our objectives are: (i) To provide an outline of Wittgenstein’s philosophical development following as a leading-thread his analysis of the sources and limits of normativity. (ii) To show how Wittgenstein constructs several explanatory models of normativity in order to gain a position free of overemphasis, one which, instead of eliminating recalcitrant phenomena, tries to make sense of them without yielding either to naturalism or to a full-fl edge metaphysics. In this respect, his stance avoids false dilemmas, such as that which contemporary philosophy faces: between constructivism and realism. (iii) To demonstrate that Wittgenstein’s conception of necessity is unintelligible when it is detached from his therapeutic method, a method which tries to juxtapose pictures with pictures in order to break the bewitchment of our intelligence by means of an unique analogy.

Suppurative mediastinitis following neck infection is an uncommon entity that carries a 40% mortality. It is most commonly associated with esophageal perforation or odontogenic abscess. The rapidity of spread has been attributed to dependent drainage from the neck into the mediastinum, negative intrathoracic pressure, and synergistic necrotizing bacterial growth. Cultures obtained usually grow streptococci and/or Bacteroides. We report the case of a 34-year-old woman with an upper respiratory infection who subsequently was found to have a para-/retropharyngeal and mediastinal abscess. Septic shock, respiratory failure, and death ensued, despite aggressive treatment with broad-spectrum antibiotics (for both aerobes and anaerobes), surgical drainage of the neck and mediastinum, and cardiorespiratory support. The danger of a rapid downhill clinical course with mortality due to suppurative mediastinitis makes early diagnosis of critical importance. All clinicians evaluating a “sore throat” should consider neck edema or gas on neck radiograms as evidence of cervical abscess, and subsequent widening of the mediastinum on chest x-ray as an ominous sign suggesting mediastinal abscess.

La cueva de Maltravieso (Cáceres) es conocida por su conjunto de arte parietal del Paleolítico superior. En el año 2002 comenzaron las intervenciones sistemáticas en la cueva, evidenciando inicialmente su potencial arqueológico como yacimiento pleistoceno. Trabajos posteriores permitieron obtener los primeros datos sobre el Paleolítico superior en la Sala de las Chimeneas: dataciones radiométricas, datos paleoecológicos, elementos simbólicos y los análisis zooarqueológico y tecnotipológico. Además, se resaltan las implicaciones del conjunto en el marco del Paleolítico superior del suroeste peninsular, donde se conocen pocos yacimientos de esta cronología (17500-18500 BP), siendo éste el primero de Extremadura. Maltravieso cave (Cáceres, Spain) is well-known thanks to its parietal art that dates from the Upper Palaeolithic. Since 2002, when systematic excavations began in the cave, its archaeological potential as a Pleistocene site was proven. This paper presents the first Upper Palaeolithic data from La Sala de las Chimeneas. That is: dating, paleoecological data, symbolic elements, and faunistic and tecnotipological analysis. Furthermore, the site’s implications in the southwestern Iberian Peninsula Upper Palaeolithic framework are highlighted, as few sites of this chronology (17500-18500 BP) are known. In fact, La Sala de las Chimeneas record is the first one known in the region of Extremadura.

A range of challenges associated with organic and other ‘low input’ (especially outdoor) livestock production systems have been identified. These include the need to identify alternative approaches for the control of parasites and gastrointestinal diseases to further reduce veterinary medicine use and antibiotic/anthelmintic resistance development. QLIF workshop 3 will summarise the fourth year’s results of the livestock subproject (SP4) of the QualityLowInputFood IP. At the same time, it will contribute to the discussion on how organic livestock farming systems are being evaluated: by their design (input) or by their performance (output). This paper summarises QLIF results from SP4 in the context of current scientific knowledge.

The potential role of nitrite as an antimicrobial substance in the stomach may be of some importance in the ecology of the gastrointestinal tract and in host physiology. It has been shown that nitrite, under the acidic conditions of the stomach, may kill gut pathogens like Salmonella enteritidis, Escherichia coli, Salmonella typhimurium, and Yersinia enterocolitica, whereas acid alone has only a bacteriostatic effect. An in vivo study was conducted in order to assess the effects of dietary nitrate on microbiota and on the health of the gut (particularly in the stomach and small intestine). 96 weaning pigs were fed a diet containing high nitrate levels (15 mg and 150 mg) and then challenged with Salmonella enterica serovar typhimurium. Differences in composition of the gut microbiota were assessed by analysing samples from the pigs: To date analysis of 48 pigs has been completed.. Preliminary results demonstrated no effect on the population densities of microbial groups either from the challenge or from nitrate intake. However, increasing the time from challenge decreased either the counts of LAB in the stomach and jejunum or of clostridia in the stomach. Bifidobacteria also decreased in the stomach contents as nitrate supplementation increased. Supplementing the feedstuff with high dietary nitrate intake and then challenging with Salmonella did not affect the gastric pH or the degree of ulceration in the pigs. The synergistic bactericidal effects of pH, nitrite and thiocyanate on seven probiotic Bifidobacterium spp. strains were also investigated in an in vitro study. The results of the in vitro study demonstrated that an inhibitory effect exists on the seven probiotic bifidobacteria investigated with an exposure longer than 2 hours and pH values < 5.0. Addition of thiocyanate also increased the susceptibility of the tested strains. In this in vitro study, the most resistant strains at all conditions were B. animalis subsp. lactis Ra 18 and P32 and B. choerinum Su 877, Su 837 and Su 891.

Food safety and health issues increased the need to use alternative procedures to antibiotics to combat pathogens in livestock. We evaluated the potential health-improving effects of both a probiotic and/or prebiotic feed formula in four series of trials. In a first and second experimental series, weaning pigs were fed respectively with different strains of Bifidobacterium spp. as probiotics and different fructo- and galacto-oligosaccharides as prebiotics. The best probiotic strains and prebiotic fiber resulting from these two series were jointly used in a third series. The composition of the cecal microbiota of the weaning pigs was analyzed and in vivo trials were conducted to evaluate the effects of the feed supplements. Bifidobacteria strains with a similar ability to develop in the hindgut had a different effect on the piglet performance depending on the dose in which they were provided. Our data also support that the presence of fructo-oligosaccharides can stimulate the occurrence of bifidobacteria in the cecum. We did however not observe an additional growth stimulus when they were supplemented with an increasing dose of bifidobacteria. In the fourth series of trials the best feed supplementation formula (1011 cfu of a Bifidobacterium animalis subps. lactis twice a day per pig) was challenged by infecting the pigs with a pathogenic strain of Salmonella.