Number Density Interpretation of Dihadron Fragmentation Functions.

We present a new quantum field-theoretic definition of fully unintegrated dihadron fragmentation functions (DiFFs) as well as a generalized version for n-hadron fragmentation functions. We demonstrate that this definition allows certain sum rules to be satisfied, making it consistent with a number density interpretation. Moreover, we show how our corresponding so-called extended DiFFs that enter existing phenomenological studies are number densities and also derive their evolution equations. Within this new framework, DiFFs extracted from experimental measurements will have a clear physical meaning.

Transversity Distributions and Tensor Charges of the Nucleon: Extraction from Dihadron Production and Their Universal Nature.

We perform the first global quantum chromodynamics (QCD) analysis of dihadron production for a comprehensive set of data in electron-positron annihilation, semi-inclusive deep-inelastic scattering, and proton-proton collisions, from which we extract simultaneously the transversity distributions of the nucleon and π^{+}π^{-} dihadron fragmentation functions. We incorporate in our fits known theoretical constraints on transversity, namely, its small-x asymptotic behavior and the Soffer bound. We furthermore show that lattice-QCD results for the tensor charges can be successfully included in the analysis. This resolves the previously reported incompatibility between the tensor charges extracted from dihadron production data and lattice QCD. We also find agreement with results for the transversity and tensor charges obtained from measurements on single-hadron production. Overall, our work demonstrates for the first time the universal nature of all available information for the transversity distributions and the tensor charges of the nucleon.

Isovector EMC Effect from Global QCD Analysis with MARATHON Data.

We report the results of a Monte Carlo global QCD analysis of unpolarized parton distribution functions (PDFs), including for the first time constraints from ratios of ^{3}He to ^{3}H structure functions recently obtained by the MARATHON experiment at Jefferson Lab. Our simultaneous analysis of nucleon PDFs and nuclear effects in A=2 and A=3 nuclei reveals the first indication for an isovector nuclear EMC effect in light nuclei. We find that while the MARATHON data yield relatively weak constraints on the F_{2}^{n}/F_{2}^{p} neutron to proton structure function ratio and on the d/u PDF ratio, they suggest an enhanced nuclear effect on the d-quark PDF in the bound proton, questioning the assumptions commonly made in nuclear PDF analyses.

MRSA infections among patients in the emergency department: a European multicentre study.

BACKGROUND: MRSA is a therapeutic concern worldwide, and a major agent of community-acquired skin and soft tissue infections (CA-SSTIs). While the US epidemiology of MRSA in CA-SSTIs is well described and reports the high prevalence of the USA300 clone, data on the European situation are lacking. OBJECTIVES: To determine the prevalence and clonal characteristics of MRSA in CA-SSTIs in seven European emergency departments. PATIENTS AND METHODS: From April to June 2015, patients presenting to the tertiary hospital emergency department with a Staphylococcus aureus CA-SSTI were prospectively enrolled. S. aureus isolates were characterized by antimicrobial susceptibility testing, detection of Panton-Valentine leucocidin encoding genes and spa-typing, MLST and/or DNA microarray. RESULTS: Two-hundred and five cases of S. aureus-associated CA-SSTIs were included, comprising folliculitis, furuncles, abscesses, paronychia, impetigo, carbuncles and cellulitis. Of the 205 cases, we report an MRSA prevalence rate of 15.1%, with a north (0%) to south (29%) increasing gradient. Fifty-one isolates were Panton-Valentine leucocidin-positive (24.9%), whether MSSA or MRSA, with a heterogeneous distribution between countries. Clonal distribution of MSSA and MRSA showed high diversity, with no predominant circulating clone and no archetypical USA300 CA-MRSA clone. CONCLUSIONS: This original prospective multicentre study highlights stark differences in European MRSA epidemiology compared with the USA, and that the USA300 CA-MRSA clone is not predominant among community-infected patients in Europe.

Nosocomial transmission of carbapenem-resistant Klebsiella pneumoniae in an Italian university hospital: a molecular epidemiological study.

AIM: To describe the phenotypic and genotypic profiles of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) strains isolated from patients with invasive infections at an Italian university hospital in order to assess the epidemiological trend. METHODS: An observational prospective study was undertaken at the University Hospital of Sassari, Italy to detect KPC-Kp strains in patients with invasive bacteraemia. Isolates were identified phenotypically; carbapenemase production was assessed using phenotypic and genotypic methods. Sequencing of blaKPC genes, pulsed-field gel electrophoresis and multi-locus sequence typing were performed. RESULTS: During the period 2015-2017, 46 cases of invasive infection with K. pneumoniae were recorded. Two-thirds (67.4%) of the patients were male, and the mean age was 69.4 years. Most patients had at least one comorbidity (56.5%) and/or had been hospitalized previously (70.5%), 81.8% had current or recent medical device use, and 85.4% had recent antibiotic exposure. The mortality rate was 52.3%. A multi-drug-resistant pattern (including carbapenems, fluoroquinolones, third-/fourth-generation cephalosporins) was shown for all K. pneumoniae isolates. KPC-3 and -2 were produced by all strains. The most common sequence types were 512 (91.3%) and 101 (8.7%), grouped into three clusters (A, A1 and B). CONCLUSIONS: A high incidence of KPC-Kp in patients with invasive infections was recorded at an Italian university hospital compared with the incidence measured before 2015. This study confirmed the importance of the KPC-3 carbapenemase variant, as reported by other Italian studies. High mortality and comorbidity rates appear to be associated with KPC-Kp infection.

VALHUDES: A protocol for validation of human papillomavirus assays and collection devices for HPV testing on self-samples and urine samples.

BACK GROUND: Systematic reviews have concluded that hrHPV DNA testing using target-amplification tests is as accurate on vaginal self-samples as on clinician-taken specimens for the detection of cervical precancer. However, insufficient evidence is available for specific HPV assay/self-sample device combinations. OBJECTIVES: The VALHUDES protocol is designed as a diagnostic test accuracy study that aims to compare the clinical sensitivity and specificity of particular hrHPV assay(s) on vaginal self-samples and first-void-urine, collected in agreement with standardized protocols, with hrHPV testing on matched clinician-taken samples. STUDY DESIGN: Five hundred enrolled women referred to a colposcopy clinic are invited to collect a first-void urine sample and one or more vaginal self-samples with particular devices before collection of a cervical sample by a clinician. Sample sets are subsequently analysed in a laboratory accredited for HPV testing. Disease verification for all enrolled patients is provided by colposcopy combined with histological assessment of biopsies. RESULTS: A first VALHUDES study has started in Belgium in December 2017 with enrolment from four colposcopy centres. The following assays are foreseen to be evaluated: RealTime High Risk HPV assay (Abbott), cobas-4800 and -6800 (Roche), Onclarity (BD), Xpert HPV (Cepheid) and Anyplex II HPV HR (Seegene). CONCLUSION: Given empirical evidence that the relative accuracy of HPV-testing on self- vs clinician-samples is robust across clinical settings, the VALHUDES protocol offers a framework for validation of HPV assay/self-sample device combinations that can be translated to a primary screening setting.

Psoas abscess ten years after ipsilateral nephrectomy for pyonephrosis.

Pyogenic abscess of the psoas muscle is a rare disease. The Authors report a recently observed case which developed 10 years after ipsilateral nephrectomy for pyonephrosis, reviewing the pertinent literature. The culture of the pus extracted only reproduced Proteus mirabilis. The relation between psoas abscess and nephrectomy is unclear. To make diagnosis is important to consider this condition in differential diagnosis in presence of fever and flank tenderness in a nephrectomized patient.

[Pinworm infestation of the appendix]. / Ossiuriasi appendicolare: nostra esperienza.

The Authors present 2 cases of enterobiasis of appendix observed on a total of 186 appendicectomies. Enterobius infestation is an uncommon cause of acute appendicitis. Preoperative diagnosis of pinworm infestation is almost impossible without clinical suspect. Parasites may produce symptoms which resemble acute appendicitis but parasitic infection rarely causes it. It is also important considered in the differential diagnosis cases that mimic Crohn's disease.

Inhibition of murine leukemia (WEHI-3B and L1210) proliferation by cholera toxin B subunit.

Cholera holotoxin produces both stimulation and inhibition of the growth of different cell populations. These opposite effects were both attributed to the enzymatic activity of the subunit A that activates adenylate cyclase, increasing the intracellular level of cAMP. We observed that the B subunit of cholera toxin produced by itself an inhibition of the 'in vitro' growth of two murine leukemia cell lines (L1210 limphoid leukemia and WEHI-3B myelomonocytic leukemia). The sensitivity of WEHI-3B cells towards cholera toxin was about 5000-times higher than that of the L1210 cells, whereas the two leukemias showed an identical sensitivity to the B subunit (IC50 = 5.10(-10) M for L1210 and 10(-10) M for WEHI-3B). The inhibition produced by the B subunit was neutralized by GM1 and in a minor degree by type II gangliosides. The two leukemias showed a remarkable difference in their gangliosides contents (L1210 cells contained GM1 (80.6%) and GM2 (19.4%), while WEHI-3B cells contained GM1 (28.2%), Fuc-GM1 (44.9%) and a band (26.9%) with a chromatographic mobility between GD1a and GD1b). The inhibition could be explained by a competitive mechanism between the B subunit and some autocrine factor binding GM1-containing receptors. Our data strengthen the suggestion to consider gangliosides as very important pleiotropic biomodulators.

Elevated serum levels of interleukin-12 in chronic progressive multiple sclerosis.

The serum levels of the heterodimeric cytokine IL-12 were measured by solid-phase ELISA in a group of healthy subjects, multiple sclerosis (MS) patients with secondary chronic progressive course of the disease and patients suffering from other neurological diseases (OND). Serum levels of IL-12 higher than 5 pg/ml (limit of sensitivity of the assay) were only found in 2/30 (6.7%) of the healthy subjects and none of the 8 subjects with OND. In contrast, IL-12 was found in the majority of CPMS patients' sera (10/15, 66.7%) with values ranging between 5.5 and 18.6 pg/ml. These results are suggestive for an up-regulated production of IL-12 in CPMS.

Prevalence of the internalization-associated gene prtF1 in a bacterial population of Streptococcus pyogenes isolated from children with acute pharyngotonsillitis before and after antibiotic therapy.

The prevalence of the internalization-associated prtF1 gene was studied in 837 isolates of Streptococcus pyogenes obtained from 713 pediatric patients presenting with acute pharyngotonsillitis before and after antibiotic therapy. Its association with macrolide resistance and with bacteriological treatment failure was determined. The bacterial population isolated from baseline pharyngeal swabs showed an overall prtF1 positivity rate of 33%. A higher prtF1 positivity was found among erythromycin-resistant strains (45%) showing, however, marked differences between the inducible (iMLS), constitutive (cMLS), and efflux pump (M) resistance phenotypes. The prevalence was statistically higher (p < 0.001) in strains belonging to iMLS (84%) and cMLS (67%) phenotypes as compared to the M phenotype (15%). Interestingly, the prevalence of the prtF1 gene was significantly lower (p = 0.04) in strains belonging to M resistance phenotype as compared to erythromycin-susceptible strains (28%). Failed bacterial eradication was demonstrated in 124 patients. The prtF1 positivity rate remained unchanged in strains isolated before and after therapy in patients treated with macrolides (9/54). On the other hand, the positivity rate for the prtF1 gene was significantly higher (p = 0.015) in strains isolated after therapy with beta-lactams (21/70) as compared to baseline isolates (6/70), indicating a differential selection imposed on the organism by these agents. Finally, a high overall eradication rate (88%) of prtF1-positive isolates, belonging to both the erythromycin-susceptible and -resistant phenotypes, was demonstrated following macrolide treatment.

Antibiotic susceptibility of group A streptococci in 2 Italian cities: Milano and Catania.

Resistance to macrolides has increasingly been reported for Group A streptococci. In this study, the in vitro antibiotic susceptibility pattern of 305 clinical isolates of S. pyogenes was determined. Strains were isolated during 1996 from pharyngeal swabs of children with uncomplicated pharyngitis living in 2 Italian cities: Milano and Catania, situated in the North and South of Italy, respectively. All isolates were found to be fully susceptible to penicillin and other beta-lactam agents tested. Susceptibility to macrolides differed markedly between the two centers with relatively high resistance rates to erythromycin being observed in Milano (30%) as compared to Catania (3%). Resistance to erythromycin was always crossed with that of the other 14- and 15-membered macrolides tested. However, resistance to josamycin and clindamycin was generally found in approximately 25% of the erythromycin-resistant (ER) strains. The erythromycin-resistant isolates from Milano and Catania (58 strains) were further subdivided into the three previously described resistance phenotypes: constitutive, inducible, and novel resistance phenotypes. The novel resistance phenotype accounted for 58% of all resistant strains, while 17% and 26% were found to be of the inducible and constitutive resistance phenotypes. Strains of the novel resistance phenotype were characterized by lower MIC values (MIC90 = 16 mg/L) to 14 and 15 carbon atom macrolides as compared to the other two phenotypes (MIC90 > 128 mg/L), and retained susceptibility to clindamycin and to josamycin, a 16 carbon atom macrolide. Resistance to tetracyclines was found in 25% to 36% of the ER isolates as compared to 2% to 10% of the susceptible strains. In particular, resistance to this agent was more commonly associated to isolates belonging to the novel and constitutive resistance phenotypes. MIC values for chloramphenicol in all isolates were within the susceptible or intermediate range; decreased susceptibility to this agent did not appear to be associated with erythromycin resistance.

High incidence of erythromycin-resistant Streptococcus pyogenes in Monza (North Italy) in untreated children with symptoms of acute pharyngo-tonsillitis: an epidemiological and molecular study.

A retrospective analysis of susceptibility data available for Group A streptococcal isolates collected between January 1990 and January 1996 at the Hospital Microbiology Laboratory of Monza (North Italy), showed a sharp rise in the erythromycin resistance rates during the last 3 years. Streptococcus pyogenes resistant to erythromycin accounted for approximately 1% of strains isolated between 1990 and 1992; the percentage then rose from 5% in 1993 to almost 39% in 1995. In January 1996, the resistance rates peaked to 81%. A prospective controlled study performed between March and May of 1996 to determine the percentage of erythromycin-resistant Group A streptococci isolated in Monza from untreated children with acute pharyngo-tonsillitis, gave further confirmation of a high rate of erythromycin resistance (47%) in this area. Molecular characterization by T-serotyping and pulse-field gel electrophoresis analysis of 25 erythromycin-resistant Group A streptococcal isolates, showed a relatively high degree of heterogeneity among these strains, demonstrating that the increased resistance is not caused by the spread of a single clone.

Molecular typing of methicillin-resistant Staphylococcus aureus by pulsed-field gel electrophoresis: comparison of results obtained in a multilaboratory effort using identical protocols and MRSA strains.

Pulsed-field gel electrophoresis (PFGE) has become the gold standard of molecular methods in epidemiological investigations. In spite of its high resolving power, use of the method has been hampered by inadequate laboratory-to-laboratory reproducibility. In the project described here we have addressed this problem by organizing a multilaboratory effort in which the same bacterial strains (subtype variants of the Iberian and Brazilian methicillin-resistant Staphylococcus aureus--MRSA--clones) were analyzed by twenty investigators in thirteen different laboratories according to an indentical protocol, which is reproduced here in detail. PFGE patterns obtained were analyzed at a central laboratory in order to identify specific technical problems that produced substandard macrorestriction patterns. The results including the specific technical problems and their most likely causes are described in this communication. Also listed are seven major epidemic clones of MRSA which have been characterized by molecular fingerprinting techniques and the prototypes of which have been deposited at the American Type Culture Collection, from where they will be available for interested investigators for the purpose of typing MRSA isolates. It is hoped that this communication will contribute to the improvement of the reproducibility and technical/aesthetic quality of PFGE analysis.

Bacteriological and clinical efficacy of various antibiotics used in the treatment of streptococcal pharyngitis in Italy. An epidemiological study.

A total of 123 community paediatricians and 23 microbiology laboratories studied the clinical and bacteriological efficacy of treatment of group A streptococcal pharyngitis in Italy. Of 1065 patients, from whom Streptococcus pyogenes was isolated, 723 returned to follow up and of these 138 (19%) still had a positive throat culture. The erythromycin resistance (ER) rate was 23.7% with resistance phenotype distribution of: 31.7% constitutive (CR), 26.6% inducible (IR) and 41.7% efflux pump (M) resistance phenotype. All strains were susceptible to the beta-lactam agents tested. CR strains were highly resistant to all 14, 15 and 16 membered macrolides with the exception of rokitamycin which showed activity against 37.8% of isolates. All phenotype M and some IR isolates were susceptible to clindamycin, rokitamycin, josamycin and spiramycin; clarithromycin was active against a small percentage of strains belonging to the IR and M phenotype. Bacterial eradication was found in 85.5, 78.7 and 75.8% of the penicillin, macrolide and cephalosporin treated groups. Genotyping of strains showed that 8.7% of the 19% of cases classified as 'failed bacterial eradication' were due to recolonization with a different isolate, observed exclusively among beta-lactams treated patients. Clinical cure was achieved in a high percentage of cases, irrespective of the antibiotic prescribed, with the best clinical efficacy being found following therapy with amoxycillin and clarithromycin (90.9%).

Antibacterial activity of tigemonam dicholate (SQ 30836) and interaction with beta-lactamases of gram-negative bacteria.

SQ 30836 is an orally absorbed salt of tigemonam, a new monobactam similar to aztreonam in structure and microbiologic properties. When assayed against 400 clinical isolates, tigemonam's activity was similar to that of aztreonam and carumonam. It was highly effective against Enterobacteriaceae but showed poor activity against gram-positive organisms. It inhibited 90% of Escherichia coli, Klebsiella, Shigella, Yersinia, Proteus, Providencia, and Morganella strains at 0.5 micrograms/mL or less, and all Salmonella and Hafnia strains at 1 micrograms/mL or less. Citrobacter, Enterobacter, and Serratia strains were less susceptible (minimum inhibitory concentrations [MIC30] of 2, 32, and 8 micrograms/mL respectively). The activity of the new compound against Enterobacteriaceae is comparable with and often higher than that of third-generation cephalosporins and oral comparison compounds. In contrast to aztreonam, tigemonam had minimal activity against Pseudomonas sp and glucose nonfermenting gram-negative bacteria. Data suggest that poor penetration through the outer membranes of Pseudomonas sp may be responsible for this failure. Tigemonam was stable to hydrolysis by plasmid-mediated and chromosomal beta-lactamases. It was more stable than aztreonam to hydrolysis by the Kl enzyme of Klebsiella and by the Proteus vulgaris beta-lactamase. Also, measurement of the IC50 (concentration of inhibitor able to reduce the activity of the enzyme by 59%) showed that tigemonam has less affinity than aztreonam for class I cephalosporinases. However, only levels of beta-lactamase, not hydrolysis rates or affinity, correlated to MICs of the two monobactams for the resistant Enterobacter and Citrobacter strains.

Antibacterial, antimycotic and trichomonicidal activity of a new nitroimidazole (EU 11100).

The antimicrobial profile of a new nitroimidazole derivative (5-nitro-1-methyl-imidazolyl-2-hydroxy-3 terbutylphenyl carbinol) has been studied. The in vitro activity of the new molecule has been evaluated against both aerobic and anaerobic bacteria, Trichomonas vaginalis, and mycetes, under suitable experimental conditions. The new compound was compared with ampicillin against aerobic bacteria; with metronidazole against anaerobic bacteria, lactobacilli and T. vaginalis; with nistatin and econazole against candida and with econazole and bifonazole against filamentous fungi. The new nitroimidazole derivative has been shown to be moderately active against some anaerobic bacteria belonging to both the Gram-positive and Gram-negative groups. Its inhibitory activity against T. vaginalis was similar to that of metronidazole.

In-vitro activity of ampicillin/sulbactam and other antibiotics against clinical isolates of Haemophilus sp. and Branhamella catarrhalis.

The ampicillin/sulbactam combination is one of several such drug combinations of a beta-lactam and suicide inhibitor having a wide spectrum of activity. These characteristics induced us to evaluate the in vitro activity of this combination towards 54 strains of Haemophilus sp. (38 beta-lactamase producers) and 20 strains of Branhamella catarrhalis (16 beta-lactamase producers). All strains were isolated from sputum, sinusal aspiration and tympanocentesis. In the case of Haemophilus sp beta-lactamase producers, minimal inhibitory concentrations of ampicillin were reduced 8 times by the use of the inhibitor; good results were also obtained for B. catarrhalis. Haemophilus influenzae, B. catarrhalis together with Streptococcus pneumoniae are recognized as the major pathogens involved in upper respiratory tract infections. The increasing frequency of beta-lactamase producing strains has impaired the use of aminopenicillins. The combination of an inhibitor and beta-lactam restore the activity of the latter, suggesting that this combination can serve as first choice in therapy.

The effect of cefepime on some immune parameters in vitro: lack of interference with mitogen-induced lymphoproliferation, immunoglobulin synthesis, IFN-gamma and IL-2 secretion and IL-2 receptor expression.

The possible interference of the novel antibiotic cefepime (CPE) with some functions of the immune system was investigated in vitro. Peripheral blood mononuclear cells (PBMC) cultured in the presence of drug concentrations ranging from 25 to 100 micrograms/ml normally maintained their responsiveness to polyclonal (PHA, Con A, PWM) mitogenic stimulation in regard to proliferative response, IgM and IgG synthesis and IFN-gamma and IL-2 secretory capacity. Moreover, PHA-induced expression of IL-2 receptors was comparable in PBMCs cultured in the presence or absence of CPE. Taken together, these data suggest that CPE does not interfere, at this specific level, with T- and B-cell mediated functions in vitro.

Efficacy and tolerability of brodimoprim od versus norfloxacin bid in the treatment of bacterial urinary tract infections.

The efficacy and tolerability of brodimoprim OD versus norfloxacin BID were studied in patients affected by bacterial urinary tract infections. The study was performed in 203 patients divided into two parallel randomized groups orally given either brodimoprim 400 mg OD on the first day followed by 200 mg OD for 2 days, or norfloxacin 400 mg BID respectively. The efficacy of treatment was evaluated by the bacterial cultures, tolerability, analysis of signs and symptoms, a complete physical examination and from laboratory data. The results showed that brodimoprim and norfloxacin in the majority of patients resulted in a reduction of fever and symptoms caused by the infective process. Of the 103 patients enrolled in the brodimoprim OD group, 99 had a complete course of therapy with a positive outcome. There was only one case of failed treatment and 3 cases which could not be evaluated because of voluntary interruption of treatment. Of the 100 patients treated with norfloxacin BID, 94 completed therapy with a positive clinical outcome and there were 4 cases of treatment failure. Thus the efficacy of brodimoprim OD appears comparable to that of norfloxacin BID in the treatment of urinary tract infections.