Deep-sequencing of Solanum commersonii small RNA libraries reveals riboregulators involved in cold stress response.

Among wild species used in potato breeding, Solanum commersonii displays the highest tolerance to low temperatures under both acclimated (ACC) and non-acclimated (NACC) conditions. It is also the first wild potato relative with a known whole genome sequence. Recent studies have shown that abiotic stresses induce changes in the expression of many small non-coding RNA (sncRNA). We determined the small non-coding RNA (sncRNAome) of two clones of S. commersonii contrasting in their cold response phenotypes via smRNAseq. Differential analysis provided evidence that expression of several miRNAs changed in response to cold stress conditions. Conserved miR408a and miR408b changed their expression under NACC conditions, whereas miR156 and miR169 were differentially expressed only under ACC conditions. We also report changes in tasiRNA and secondary siRNA expression under both stress conditions. Our results reveal possible roles of sncRNA in the regulatory networks associated with tolerance to low temperatures and provide useful information for a more strategic use of genomic resources in potato breeding.

Birmingham epidermolysis severity score and vitamin D status are associated with low BMD in children with epidermolysis bullosa.

Bone status impairment represents a complication of generalized forms of epidermolysis bullosa (EB); however, the prevalence and the main determinants of this event in localized forms remain poorly defined. Birmingham epidermolysis bullosa severity (BEBS) score and 25-hydroxyvitamin D levels are strongly associated with low bone mass, suggesting that vitamin D may play a potential beneficial role in bone health. Further longitudinal studies are needed in order to confirm this hypothesis. INTRODUCTION: Bone status impairment represents a complication of generalized forms of EB; thus, we aimed to estimate the prevalence of low bone mass, to examine mineralization differences in various EB subtypes and to identify the most important determinants of bone impairment in children with either generalized or localized EB. METHODS: An observational study of 20 children (11 males; mean age ± standard deviation, 11.7 ± 3.9 years) with EB was performed. Clinical history, physical examination, laboratory studies, X-ray of the left hand and wrist for bone age, and dual energy X-ray absorptiometry scans of the lumbar spine were obtained. Areal bone mineral density (aBMD Z-scores) and bone mineral apparent density were related to the BEBS score. RESULTS: Areal BMD Z-score (mean -1.82 ± 2.33, range, -7.6-1.7) was reduced (<-2 SD) in 8 patients (40%), whereas aBMD Z-score adjusted for bone age was low in 7 patients (35%). BEBS score and 25-hydroxyvitamin D serum levels were the most important elements associated with aBMD (P = 0.0001 and P = 0.016, respectively). A significant correlation between the aBMD Z-score and area of skin damage, insulin-like growth factor-1, C-reactive protein, and sodium serum levels was also found. CONCLUSIONS: Low aBMD can be considered a systemic complication of EB, primarily associated with BEBS score and 25-hydroxyvitamin D levels. Therefore, longitudinal evaluation of bone status is ongoing in these patients to define whether vitamin D supplementation would prevent, or at least reduce, bone status impairment.

Anti-bacterial effect of essential oil from Xanthium strumarium against shiga toxin-producing Escherichia coli.

Shiga toxin-producing Escherichia coli (STEC) serotype O157:H7 is one of the most important human pathogenic microorganisms, which can cause life-threatening infections. Xanthium strumarium L. is a plant with anti-bacterial activity against gram-negative and gram-positive bacteria. This study aims to demonstrate in vitro efficacy of the essential oil (EO) extracted from Xanthium strumarium L. against E. coli O157:H7. Using the agar test diffusion, the effect of Xanthium strumarium L. EO (5, 10, 15, 30, 60, and 120 mg/mL) was verified at each of the four different growth phases of E. coli O157:H7. Cell counts of viable cells and colony forming unit (CFU) were determined at regular time points using Breed's method and colony counting method, respectively. No viable cell was detectable after the 1 hour-exposure to X. strumarium EO at 30, 60, and 120 mg/mL concentrations. No bacterial colony was formed after 1 h until the end of the incubation period at 24 h. At lower concentrations, the number of bacteria cells decreased and colonies could be observed only after incubation. At the exponential phase, the EO at 15 mg/mL was only bacteriostatic, while from 30 mg/mL started to be bactericidal. X. strumarium EO antibacterial activity against Shiga toxin-producing E. coli O157:H7 is dependent on EO concentration and physiological state of the microorganisms tested. The best inhibitory activity was achieved during the late exponential and the stationary phases.

How to manage neonatal tuberculosis.

This article reports the recommendations for managing neonatal tuberculosis (TB) drawn up by a group of Italian scientific societies. The Consensus Conference method was used, and relevant publications in English were identified through a systematic review of MEDLINE and the Cochrane Database of Systematic Reviews from their inception until 31 December 2014. Group experts concluded that if suspicion is aroused, it is necessary to undertake promptly all of the investigations useful for identifying the disease not only in the newborn, but also in the mother and family contacts because a diagnosis of TB in the family nucleus can guide its diagnosis and treatment in the newborn. If the suspicion is confirmed, empirical treatment should be started. Breast-fed newborns being treated with isoniazid should be given pyridoxine supplementation at a dose of 1 mg kg(-1) day(-1). Mothers with active-phase TB can breast-feed once they have become smear negative after having received appropriate treatment.

Streptococcus salivarius 24SMB administered by nasal spray for the prevention of acute otitis media in otitis-prone children.

This paper reports the results of the first study in which Streptococcus salivarius 24SMB, a safe α-haemolytic strain capable of producing bacteriocin-like substances with significant activity against acute otitis media (AOM) pathogens, was intranasally administered in an attempt to reduce the risk of new episodes of AOM in otitis-prone children. In this prospective, randomized, double-blind, placebo-controlled study, 100 children aged 1-5 years with histories of recurrent AOM were randomized 1:1 to receive an intranasal S. salivarius 24SMB or placebo twice daily for 5 days each month for 3 consecutive months. Fifty treated children and 47 who received placebo who were compliant with study protocol were followed monthly for 6 months. The number of children who did not experience any AOM was higher among the children treated with the S. salivarius 24SMB preparation than among those in the placebo group (30.0 vs 14.9%; p = 0.076). Moreover, the number of children who received antibiotics during the study period was lower among the children treated with S. salivarius 24 SMB than among those who received placebo (70 vs 83.0%; p = 0.13). Compared with the children who were not colonized by S. salivarius 24SMB after treatment, the number of colonized children who experienced any AOM was significantly lower (42.8 vs 13.6%; p = 0.03). Similar results were observed when the children treated with antibiotics for AOM were analysed (67.8 vs 95.5%; p = 0.029). This study revealed the ability of intranasally administered S. salivarius 24SMB to reduce the risk of AOM in otitis-prone children.

Immunostimulants and prevention of recurrent respiratory tract infections.

Recurrent respiratory tract infections (RRTIs) are very common in children and a major challenge for pediatricians. They affect the children's quality of life, cause absences from school and lost parental working days, and repeated medical examinations, hospital admissions as well as antibiotic therapies lead to high costs for society. Given their prevalence and clinical importance, various prevention strategies have been developed. One of the most widely used is the administration of immunostimulants: i.e. molecules of bacterial or synthetic origin that interact with immunological mechanisms in vitro and in vivo. A number of studies have investigated their effects on cellular and innate immunity, and their clinical efficacy, but there is no consensus as to their real usefulness. The main aim of this review is to analyse the available data concerning the activity and efficacy of immunostimulants in preventing pediatric RRTIs. The majority of studies have shown that the number of infections decreases after immunostimulant treatment, but they are affected by various methodological weaknesses. Further studies are urgently needed to confirm whether, when and which immunostimulants should be used.

Role of vitamin D in children with respiratory tract infection.

It has recently been shown that vitamin D (VitD) plays an important role in host defences, inflammation and immunity. We reviewed PubMed and selected all of the studies published over the last 15 years concerning VitD deficiency and VitD supplementation in children with respiratory tract infections. Our analysis showed that VitD seems to be very important because of its part in the complexity of the immune system. However, there are few pediatric studies and most have various limitations. First of all, the literature mainly refers to studies concerning the prevalence of VitD insufficiency and deficiency in specific pathologies. Secondly, it is extremely difficult to identify a common specific range of normal, insufficient and deficient VitD levels. Thirdly, the available studies of VitD supplementation often combined VitD with the use of other micronutrients, thus obscuring the role of VitD itself. Finally, different doses have been used for VitD supplementation. These observations clearly highlight the fact that further studies are needed to evaluate the impact of VitD deficiency and insufficiency in terms of the epidemiology and outcomes of pediatric respiratory tract infection, and whether VitD supplementation favours a positive outcome.

Hypertonic saline is more effective than normal saline in seasonal allergic rhinitis in children.

Allergic rhinitis (AR) is a very common childhood disease that is associated with a significant reduction in the patients' quality of life. Its treatment combines educating the patients and their parents, immunotherapy and drug administration. However, even the best approach does not relieve the symptoms of a number of patients. Alternative therapies are particularly needed for children because the fear of adverse events frequently reduces parental compliance to the prescribed drugs, and immunotherapy is less easy to administer than in adults. In this prospective investigator-blinded study we evaluated whether children, with a documented history of seasonal grass pollen-related AR, benefit from nasal irrigation by assessing the effects on nasal signs and symptoms, on middle ear effusion and on adenoidal hypertrophy. We randomized children aged 5 to 9 years (median age 82 months) to normal saline or hypertonic saline (a 2.7% sodium chloride solution), administered twice-daily using a disposable 20 ml syringe, or no treatment. Nasal symptoms (rhinorrhea, itching, sneezing, nasal obstruction), swelling of turbinates, adenoid hypertrophy or middle ear effusion were assessed at baseline and after 4 weeks of treatment. Two hundred and twenty children (normal saline: 80; hypertonic saline: 80; no treatment: 60) completed the study. After four weeks, all the considered items were significantly reduced in the group receiving hypertonic saline (P < 0.0001), whereas in the group receiving normal saline only rhinorrhea (P = 0.0002) and sneezing (P = 0.002) were significantly reduced. There was no significant change in any of the items in the control group. The duration of oral antihistamines was significantly lower in the children receiving hypertonic saline than in those treated with normal saline or in controls. No adverse events were reported and parental satisfaction and compliance with the procedure were globally very good, regardless of the solution used. Using our procedure, hypertonic saline is effective, inexpensive, safe, well tolerated and easily accepted by children with seasonal grass pollen-related AR and their parents. Our data suggest that nasal irrigation with hypertonic saline might be included in the wide spectrum of therapies recommended for grass-pollen AR.

Efficacy of increasing dosages of clarithromycin for treatment of experimental Mycoplasma pneumoniae pneumonia.

OBJECTIVES: Mycoplasma pneumoniae respiratory infection is a common cause of acute respiratory infection in children and adults. We evaluated the efficacy of increasing dosages of clarithromycin for the optimized therapy of M. pneumoniae respiratory infection in a mouse model. METHODS: BALB/c mice were intranasally inoculated once with M. pneumoniae or SP4 broth (control). Groups of mice were treated with increasing dosages of clarithromycin (10, 25 or 75 mg/kg/day) or placebo subcutaneously daily. Groups of mice were evaluated after 1, 2, 3, 6 and 12 days of therapy. Outcome variables included quantitative M. pneumoniae culture, histopathological score of the lungs, bronchoalveolar lavage (BAL) cytokine/chemokine/growth factor concentrations and plethysmography after aerosolized methacholine to assess airway hyperresponsiveness. RESULTS: Elevated dosages of clarithromycin resulted in greater antimicrobial efficacy with significantly reduced M. pneumoniae quantitative cultures (P < 0.05), as well as greater improvement in markers of disease severity with significantly reduced lung histopathology scores, BAL cytokine concentrations and airway hyperresponsiveness (P < 0.05). CONCLUSIONS: Escalated dosing of clarithromycin resulted in significantly greater therapeutic efficacy in the treatment of experimental M. pneumoniae respiratory infection.

Use of complementary and alternative medicine in children with recurrent acute otitis media in Italy.

Controlling environmental factors, chemoprophylaxis, immunoprophylaxis and surgery are considered possible means of preventing recurrent acute otitis media (RAOM), but there are no available data concerning the paediatric use of complementary and alternative medicine (CAM). We evaluated the uses of CAM (homeopathy and/or herbal medicine) as means of preventing AOM in children with a history of RAOM. Eight hundred and forty Italian children with RAOM (≥3 episodes in six months) aged 1-7 years were surveyed in 2009 using a face-to-face questionnaire, filled by parents or caregivers, that explored the prevalence, determinants, reasons, cost, and perceived safety and efficacy of CAM. About one-half (46%) of the children used CAM, significantly more than the number who used immunoprophylaxis (influenza vaccine 15%; p<0.05), PCV-7 34%; p<0.05) or chemoprophylaxis (2%; p<0.001). Use of CAM in the family was the only important factor positively associated with the use of CAM in children (adjusted OR 7.94; 95% CI: 5.26-11.99). The main reasons for using CAM were a fear of the adverse effects of conventional medicine (40%) and to increase host defences (20%). CAM was widely seen as safe (95%) and highly effective (68%). CAM prescribers were paediatricians in 50.7% of cases; self-initiation was reported by 23% of respondents. CAM expenditure was between Euro 25 and Euro 50/month in 27.6% of cases and ≥ Euro 50/month in 16%. Children with RAOM should be considered among the categories of subjects likely to be using CAM. Together with the fact that paediatricians are the main prescribers, this is worrying because of the current lack of evidence regarding the efficacy, safety and cost-effectiveness of CAM in the prevention of RAOM.

Effectiveness of a propolis and zinc solution in preventing acute otitis media in children with a history of recurrent acute otitis media.

Recurrent acute otitis media (rAOM) is frequently encountered in infants and children and the lack of any definitive treatment has led parents and physicians to try complementary and alternative therapies. We evaluated the efficacy of a propolis and zinc suspension in preventing AOM in 122 children aged 1-5 years with a documented history of rAOM, who were prospectively, blindly, randomized 1:1 to receive the suspension plus elimination of environmental risk factors or elimination of environmental risk factors only. AOM- and respiratory-related morbidity were assessed at study entry and every four weeks. In the 3-month treatment period AOM was diagnosed in 31 (50.8%) children given the propolis and zinc suspension and in 43 (70.5%) controls (p=0.04). The mean number of episodes of AOM per child/month was 0.23+/-0.26 in the propolis and zinc group and 0.34+/-0.29 in controls (reduction 32.0%, p=0.03). The administration of a propolis and zinc suspension to children with a history of rAOM can significantly reduce the risk of new AOM episodes and AOM-related antibiotic courses, with no problem of safety or tolerability, and with a very good degree of parental satisfaction. No effect can be expected on respiratory infections other than AOM.

Feedback dose alteration significantly affects probability of pathogen eradication in nosocomial pneumonia.

Nosocomial pneumonia (NP) is associated with considerable morbidity and mortality. Data have shown that inadequate initial antibiotic therapy is a major risk for infection-attributed mortality. The aim of the present study was to measure antibiotic concentration and minimum inhibitory concentration (MIC) in infected hospitalised patients early in therapy, in order to determine whether dose alterations, in those with low drug concentrations, could affect outcomes. Only patients treated with aminoglycosides, fluoroquinolones, and beta-lactams were evaluated. MICs were determined using standard National Committee for Clinical Laboratory Standards procedures. Antibiotics were assayed using validated high-performance liquid chromatographic methods. Pharmacokinetic/pharmacodynamic markers adopted were: aminoglycoside peak/MIC ratio >or=8 mg L(-1); fluoroquinolone peak/MIC >or=10 mg L(-1); beta-lactam peak/MIC >or=4 mg L(-1) and time that plasma levels remain above the MIC >or=70%. 638 patients with NP were included in the study. In 205 patients, both drug concentration and isolate MIC were available, while in other patients, used as controls, one or both parameters were lacking. For clinical outcome, the Acute Physiology and Chronic Health Evaluation II score (p<0.0001), the presence of combination therapy (p = 0.0014) and whether both MIC and drug concentration(s) were measured (p = 0.0002) significantly affected the probability of a good outcome. For microbiological outcome, the MIC for the beta-lactams (

A pilot study on prevention of catheter-related urinary tract infections with fluoroquinolones.

The objective of this multicenter, randomized, controlled, parallel group trial was to evaluate the efficacy of levofloxacin 250 mg oral, once daily (LVFX), placebo one tablet oral once daily (Placebo [P] group) and ciprofloxacin (CPFX) 500 mg oral, twice daily (single blind), prophylaxis in preventing bacteriuria (> or = 10(3) CFU/ml) in post-surgical catheterized patients. In the modified intention-to-treat (M-ITT) population of the 82 enrolled patients, negative bacteriuria was observed in 92% of LVFX group, in 80% of P group and in 100% of CPFX group while in the per-protocol (PP) population figures were: 100%, 86.4% and 100% respectively. Only one symptomatic urinary tract infection and one surgical wound infection were observed in the P group. Both drugs were well tolerated, showing a safety profile comparable to placebo. The high frequency of negative bacteriuria in the placebo group sounds encouraging as it underlines that the adoption of closed urinary drainage system catheters in hospital setting may reduce the frequency of hospital-acquired infections.

[Management of serious bacterial infections: general considerations]. / La gestione delle infezioni batteriche gravi: considerazione generali.

Many efforts have been made in the recent years to improve the prognosis of severe bacterial infections by reducing the risk of treating the patients inadequately. The reasons responsible for inadequate treatment have been intensively studied and antibiotic resistance has been identified as one of the main risks. Currently different strategies are considered to optimize antibiotic therapy, such as the adoption of local guidelines, de-escalation, rotation and association therapies. Each appears to prove efficacy in the containment of resistance and improvement of outcome; however, further studies, continuous monitoring of the epidemiology of severe infections and antibiotic resistance, and finally, availability of new drugs are needed. It is the authors' opinion that, despite the importance of guidelines for the optimal treatment and most appropriate management of severe infections, closer collaboration should be established between the medical staff in the wards and IDS, who can bridge the gap between the guidelines and the individual needs of the patient, thereby improving the decision-making process. The IDS, as consultant in different medical and surgical wards and as a member of the Infectious Diseases Control local Committees, can interact at different levels and can improve the management of severe bacterial infections.

Use of antimicrobial agents for community-acquired lower respiratory tract infections in hospitalised children.

Data collected from 613 children aged 2-14 years who had been hospitalized for acute bronchitis, wheezing, or pneumonia were analysed to evaluate the prescribing practices of pediatricians treating community-acquired lower respiratory tract infection. Antibiotics were prescribed for 92.1% of the children: 85% had acute bronchitis, 72% had wheezing, and 97.9% had pneumonia. A high frequency of antibiotic overuse and inappropriate prescriptions was noted. In order to contain costs and limit the risk of resistant bacteria emerging, it is urgent that pediatricians and parents be educated in the proper use of antibiotics.

Evaluation and use of plant biodiversity for food and pharmaceuticals.

Many epidemiological studies have shown the importance of fruit and vegetables in the human diet so as to prevent the onset of cardiovascular disease and several forms of cancer. The use for food and pharmaceuticals of two of the most widely grown and genetically well-known species in the world, the tomato and the potato, is reviewed. Tomatoes are important sources of vitamin C, potassium, folic acid and carotenoids such as lycopene and beta-carotene. It has been demonstrated that lycopene has anti-oxidant properties and interferes with the growth of cancerous cells. At the Department of Agronomy and Plant Genetics in Portici, interesting results have been obtained with the constitution of stable tomato hybrids having a high content of lycopene and vitamin C. Many of the parental lines used in constituting the hybrids come from interspecific crosses. Potato is also very important in the human diet for its content of high quality proteins, mineral salts and vitamins and it has many medicinal properties. The use of diploid wild species to transfer traits such as high content of vitamin C, mineral salts and high quality proteins into the cultivated potato through ploidy manipulation is discussed.

Immunoactivity of pidotimod against episodes of recurrent tonsillitis in childhood.

The therapeutic efficacy of the synthetic immunostimulant pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) was evaluated in a double-blind placebo-controlled study in parallel groups in the management of recurrences in 235 children with recurrent tonsillitis. The ambulant study provided for 15 days of treatment with two oral vials of pidotimod 400 mg or placebo daily, in accordance with a randomisation list, 60 days of treatment with one oral vial of pidotimod 400 mg or placebo daily, and a 90-day follow-up period. The total trial period was 165 days. In addition to evaluating the number of tonsillitis recurrences which occurred during the 75 days of treatment and the 90-day follow-up period, the number of days on which the principal symptoms of the illness were present and on which drugs such as antibiotics or anti-inflammatory agents were used concomitantly, as well as the number of days' absence from school, were analyzed. The findings showed that, taking the treatment phase and the three-month follow-up period together, pidotimod significantly reduces the incidence of inflammatory upper airways episodes. The very low incidence of adverse effects, which was the same as that in the placebo group, confirmed the excellent safety of the product.

Prevalence of fluoroquinolone resistance in Europe. Study Group 'Bacterial Resistance' of the Paul-Ehrlich-Society for Chemotherapy e. V.

Since 1984, when the first fluoroquinolone, norfloxacin, was marketed in Europe, there has been a marked increase in the usage of this class of drugs. In order to evaluate the influence of this drug usage on the prevalence of resistance to fluoroquinolones in clinical isolates of the family Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus, coagulase-negative staphylococci and Enterococcus faecalis we reviewed the susceptibility data from four collaborative surveys conducted between 1983 and 1990 by the Study Group 'Bacterial Resistance' of the Paul-Ehrlich-Society for Chemotherapy. All participating laboratories used the same standardized methods. Minimal inhibitory concentrations were determined by the broth microdilution method. More than 20,000 bacterial strains were tested. The results are presented for ciprofloxacin, which is regarded as the representative of the fluoroquinolones. Using > or = 4 mg/l as a breakpoint for resistance to ciprofloxacin, the prevalence of resistant strains of the family Enterobacteriaceae in Central Europe between 1983 and 1990 remained below 1%. In contrast, the resistance rates in P. aeruginosa were 0.7%, 1.0%, 3.8% and 7.0%, in S. aureus 0%, 0.5%, 6.6% and 6.8%, and in E. faecalis 2.2%, 0.7%, 4.9% and 7.7% in 1983, 1986, 1989 and 1990, respectively. The latest study carried out in cooperation with 78 laboratories from 12 European countries revealed great differences in the prevalence of resistance to fluoroquinolones from one species to another ranging from 0% with Proteus vulgaris and Salmonella spp. to 26.7% with Providencia stuartii.(ABSTRACT TRUNCATED AT 250 WORDS)

Topical ciprofloxacin vs intramuscular gentamicin for chronic otitis media.

Clinical and bacteriological efficacy of topical ciprofloxacin hydrochloride was compared with that of intramuscular gentamicin sulfate in two groups composed of 30 patients each, all of whom were affected by chronic otitis media in the acute stage. Antibiotics were randomly given for 5 to 10 days according to the following schedules: ciprofloxacin hydrochloride, four drops (250 mg/mL in saline solution) administered locally twice a day, or gentamicin sulfate, 80 mg administered intramuscularly twice a day. We admitted to the study only adult patients affected by chronic otitis media in the acute stage with perforation of the tympanic membrane, without cholesteatoma, whose bacteriological culture was positive for Pseudomonas susceptible in vitro to ciprofloxacin and gentamicin. The clinical and bacteriological response was stated 12 hours after the interruption of the treatment, and 2 and 3 weeks later (follow-up). A favorable clinical result was observed in 26 (87%) of 30 patients under ciprofloxacin treatment; in 30 patients receiving gentamicin, a favorable clinical response was observed in 20 (66%) and bacteriological eradication in 13 (43%). No relapse at the follow-up was observed. Topical ciprofloxacin seems to be more effective than intramuscular gentamicin in curing Pseudomonas-caused chronic otitis media in the acute stage.