Dynamic and static computer-assisted implant surgery for completely edentulous patients. A proof of a concept.

OBJECTIVES: To assess the accuracy and patient reported outcome measures (PROMs) of the computer-guided "double factor" technique for treating fully edentulous patients. METHODS: A proof of concept prospective study was designed. Ten consecutive patients requiring full arch dental implant supported rehabilitation in a private practice were enrolled between October 2021 and March 2022. All patients were treated by means of an All-on-four®, and implants were planned and placed according to the "double factor" technique. This technique merges the static and dynamic computer-guided surgical approach in the same surgery. The primary outcome was the accuracy of implant placement, measured by overlapping post- and pre-operative cone-beam computerized tomography with the implant planning. Additionally, PROMs and patient quality of life after surgery were evaluated using different questionnaires. Descriptive and bivariate data analyses were performed. Statistical significance was considered for p < 0.05. RESULTS: A total of 48 implants were placed using the "double factor" technique, and 12 full-arch immediate loading prostheses were delivered. The mean angular deviation was 3.74° (standard deviation [SD]: 2). The total linear deviation at the apex and platform of the implant was 1.25 mm (SD: 0.55) and 1.42 mm (SD: 0.64), respectively. No statistically significant differences were found between tilted and axial implants, the upper and lower jaw, or the right and left side. High self-reported satisfaction was registered, and the Oral Health Impact Profile-14 (OHIP-14) score improved postoperatively (p = 0.002). CONCLUSIONS: The "double factor" technique is a valid and accurate treatment approach for fully edentulous patients. CLINICAL SIGNIFICANCE: The double factor technique merges the advantages of both the dynamic and static computer assisted surgery approaches, affording accurate and predictable results when treating fully edentulous patients in a minimally invasive manner.

Dynamic and static computer-guided surgery using the double-factor technique for completely edentulous patients: A dental technique.

A novel computer-assisted surgery (CAS) technique that merges dynamic and static CAS approaches to treat completely edentulous patients with dental implants is described. Radiographic and surgical stents are designed with specific fiducial markers that are recognized by the static and dynamic CAS software program. During the surgical procedure, implants are placed following the static surgical guide and the indications from the dynamic navigation system. This technique combines the advantages of static and dynamic CAS approaches to allow accurate and predictable minimally invasive implant placement.

Epidemiology and population structure of Haemophilus influenzae causing invasive disease.

This study provides an update on invasive Haemophilus influenzae disease in Bellvitge University Hospital (2014-2019), reporting its evolution from a previous period (2008-2013) and analysing the non-typeable H. influenzae (NTHi) population structure using a clade-related classification. Clinical data, antimicrobial susceptibility and serotyping were studied and compared with those of the previous period. Population structure was assessed by multilocus sequence typing (MLST), SNP-based phylogenetic analysis and clade-related classification. The incidence of invasive H. influenzae disease remained constant between the two periods (average 2.07 cases per 100 000 population), while the 30 day mortality rate decreased (20.7-14.7 %, respectively). Immunosuppressive therapy (40 %) and malignancy (36 %) were the most frequent comorbidities. Ampicillin and fluoroquinolone resistance rates had increased between the two periods (10-17.6 % and 0-4.4 %, respectively). NTHi was the main cause of invasive disease in both periods (84.3 and 85.3 %), followed by serotype f (12.9 and 8.8 %). NTHi displayed high genetic diversity. However, two clusters of 13 (n=20) and 5 sequence types (STs) (n=10) associated with clade V included NTHi strains of the most prevalent STs (ST3 and ST103), many of which showed increased frequency over time. Moreover, ST103 and ST160 from clade V were associated with ß-lactam resistance. Invasive H. influenzae disease is uncommon, but can be severe, especially in the elderly with comorbidities. NTHi remains the main cause of invasive disease, with ST103 and ST160 (clade V) responsible for increasing ß-lactam resistance over time.

Bronchial microbiome, PA biofilm-forming capacity and exacerbation in severe COPD patients colonized by P. aeruginosa.

AIM: The bronchial microbiome of severe chronic obstructive pulmonary disease patients colonized by Pseudomonas aeruginosa was analyzed using 16S rRNA gene sequencing to identify differences related to biofilm-forming capacity. PATIENTS & METHODS: Patient sputum samples from 21 patients were studied. RESULTS: Statistically significant differences related to biofilm-forming capacity were only found for genera with relative abundances <1%, and Fusobacterium was over-represented when biofilm-forming capacity was high. Genera with relative abundances >50% which increased from baseline were observed in 10/14 exacerbations, but corresponded to Pseudomonas only in three episodes, while other pathogenic genera were identified in seven. CONCLUSION: The bronchial microbiome shows differences according with P. aeruginosa biofilm-forming capacity. Pathogenic microorganisms other than P. aeruginosa cause a significant part of the exacerbations in colonized chronic obstructive pulmonary disease patients.

Bacterial Lysis through Interference with Peptidoglycan Synthesis Increases Biofilm Formation by Nontypeable Haemophilus influenzae.

Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen that mainly causes otitis media in children and community-acquired pneumonia or exacerbations of chronic obstructive pulmonary disease in adults. A large variety of studies suggest that biofilm formation by NTHi may be an important step in the pathogenesis of this bacterium. However, the underlying mechanisms involved in this process are poorly elucidated. In this study, we used a transposon mutant library to identify bacterial genes involved in biofilm formation. The growth and biofilm formation of 4,172 transposon mutants were determined, and the involvement of the identified genes in biofilm formation was validated in in vitro experiments. Here, we present experimental data showing that increased bacterial lysis, through interference with peptidoglycan synthesis, results in elevated levels of extracellular DNA, which increased biofilm formation. Interestingly, similar results were obtained with subinhibitory concentrations of ß-lactam antibiotics, known to interfere with peptidoglycan synthesis, but such an effect does not appear with other classes of antibiotics. These results indicate that treatment with ß-lactam antibiotics, especially for ß-lactam-resistant NTHi isolates, might increase resistance to antibiotics by increasing biofilm formation. IMPORTANCE Most, if not all, bacteria form a biofilm, a multicellular structure that protects them from antimicrobial actions of the host immune system and affords resistance to antibiotics. The latter is especially disturbing with the increase in multiresistant bacterial clones worldwide. Bacterial biofilm formation is a multistep process that starts with surface adhesion, after which attached bacteria divide and give rise to biomass. The actual steps required for Haemophilus influenzae biofilm formation are largely not known. We show that interference with peptidoglycan biosynthesis increases biofilm formation because of the release of bacterial genomic DNA. Subinhibitory concentrations of ß-lactam antibiotics, which are often prescribed to treat H. influenzae infections, increase biofilm formation through a similar mechanism. Therefore, when ß-lactam antibiotics do not reach their MIC in vivo, they might not only drive selection for ß-lactam-resistant clones but also increase biofilm formation and resistance to other antimicrobial compounds.

Description of the Characteristics of Multiple Sclerosis Patients in the Region of Valencia (Spain) Who Requested Treatment with Disease-Modifying Drugs during the 2005-2014 Decade.

BACKGROUND: More than 3,000 multiple sclerosis (MS) patients were treated with disease-modifying drugs (DMDs) in the Region of Valencia during 2005-2014. We aimed at describing the demographic and clinical characteristics of MS patients who requested treatment with DMDs, variations in their use, and the factors associated with change to second-line therapies during this decade. METHODS: A retrospective cohort study with information from Subcomité Especializado de Medicamentos de Alto Impacto Sanitario y/o Económico registers. A statistical analysis was run in 2 phases: descriptive analysis of the sample using classical statistical methods, and of DMD trend by a chi-square test for linear trends; analytic analysis to examine the factors associated with change to second-line treatment (logistic regression model). RESULTS: We selected 2,205 patients (mean age 32.12, SD 9.64; 70% females, and 86.6% remising-remitting MS (RRMS)); 1,012 patients were attended to in highly specialized MS units (45.8%); 525 in monographic units (23.8%); and 668 in general units (30.2%). DMD prescriptions increased, and glatiramer acetate was more widespread at the end of the period (35.4%). CONCLUSION: Variability in access to different treatments was slight. The younger the patient, the higher the risk of first-line RRMS treatment failing in female gender and first treatment with interferon.

Identification of Haemophilus haemolyticus in clinical samples and characterization of their mechanisms of antimicrobial resistance.

OBJECTIVES: The objectives of this study were to establish the frequency of Haemophilus haemolyticus in clinical samples, to determine the antimicrobial resistance rate and to identify the mechanisms of resistance to ß-lactams and quinolones. METHODS: An updated database was used to differentiate between MALDI-TOF MS results for Haemophilus influenzae and H. haemolyticus. Antimicrobial susceptibility was studied by microdilution, following EUCAST criteria. The ß-lactamase types were identified by PCR analysis of isolates that tested positive for nitrocefin hydrolysis. Mutations in the ftsI gene were identified in isolates with ampicillin MICs ≥0.25 mg/L. Mutations in the quinolone resistance-determining region (QRDR) were identified in isolates with ciprofloxacin MICs ≥0.5 mg/L. RESULTS: Overall, we identified 69 H. haemolyticus isolates from 1706 clinical isolates of Haemophilus spp. from respiratory, genital, invasive, and other infection sources. The frequency of H. haemolyticus was low in respiratory samples compared with that of H. influenzae, but in genital-related samples, the frequency was similar to that of H. influenzae. We found low antimicrobial resistance rates among H. haemolyticus isolates, with 8.7% for ampicillin, 8.7% for co-trimoxazole, 7.2% for tetracycline and 4.3% for ciprofloxacin. Mutations in the ftsI gene classified the isolates into four groups, including the newly described Group Hhae IV, which presents mutations in the ftsI gene not identified in H. influenzae and H. haemolyticus type strains. Three ciprofloxacin-resistant H. haemolyticus isolates with mutations affecting GyrA and ParC were identified. CONCLUSIONS: The frequency of H. haemolyticus was low, especially in respiratory samples, where H. influenzae is the main pathogen of this genus. Although antimicrobial resistance rates were low, three ciprofloxacin-resistant H. haemolyticus clinical isolates have been identified for the first time.

Molecular characterization of fluoroquinolone resistance in nontypeable Haemophilus influenzae clinical isolates.

Nontypeable Haemophilus influenzae (NTHi) is a common cause of respiratory infections in adults, who are frequently treated with fluoroquinolones. The aims of this study were to characterize the genotypes of fluoroquinolone-resistant NTHi isolates and their mechanisms of resistance. Among 7,267 H. influenzae isolates collected from adult patients from 2000 to 2013, 28 (0.39%) were ciprofloxacin resistant according to Clinical and Laboratory Standards Institute (CLSI) criteria. In addition, a nalidixic acid screening during 2010 to 2013 detected five (0.23%) isolates that were ciprofloxacin susceptible but nalidixic acid resistant. Sequencing of their quinolone resistance-determining regions and genotyping by pulse-field gel electrophoresis and multilocus sequence typing of the 25 ciprofloxacin-resistant isolates available and all 5 nalidixic acid-resistant isolates were performed. In the NTHi isolates studied, two mutations producing changes in two GyrA residues (Ser84, Asp88) and/or two ParC residues (Ser84, Glu88) were associated with increased fluoroquinolone MICs. Strains with one or two mutations (n = 15) had ciprofloxacin and levofloxacin MICs of 0.12 to 2 µg/ml, while those with three or more mutations (n = 15) had MICs of 4 to 16 µg/ml. Long persistence of fluoroquinolone-resistant strains was observed in three chronic obstructive pulmonary disease patients. High genetic diversity was observed among fluoroquinolone-resistant NTHi isolates. Although fluoroquinolones are commonly used to treat respiratory infections, the proportion of resistant NTHi isolates remains low. The nalidixic acid disk test is useful for detecting the first changes in GyrA or in GyrA plus ParC among fluoroquinolone-susceptible strains that are at a potential risk for the development of resistance under selective pressure by fluoroquinolone treatment.

Clinical and molecular epidemiology of haemophilus influenzae causing invasive disease in adult patients.

OBJECTIVES: The epidemiology of invasive Haemophilus influenzae (Hi) has changed since the introduction of the Hi type b (Hib) vaccine. The aim of this study was to analyze the clinical and molecular epidemiology of Hi invasive disease in adults. METHODS: Clinical data of the 82 patients with Hi invasive infections were analyzed. Antimicrobial susceptibility, serotyping, and genotyping were studied (2008-2013). RESULTS: Men accounted for 63.4% of patients (whose mean age was 64.3 years). The most frequent comorbidities were immunosuppressive therapy (34.1%), malignancy (31.7%), diabetes, and COPD (both 22%). The 30-day mortality rate was 20.7%. The majority of the strains (84.3%) were nontypeable (NTHi) and serotype f was the most prevalent serotype in the capsulated strains. The highest antimicrobial resistance was for cotrimoxazole (27.1%) and ampicillin (14.3%). Twenty-three isolates (32.9%) had amino acid changes in the PBP3 involved in resistance. Capsulated strains were clonal and belonged to clonal complexes 6 (serotype b), 124 (serotype f), and 18 (serotype e), whereas NTHi were genetically diverse. CONCLUSIONS: Invasive Hi disease occurred mainly in elderly and those with underlying conditions, and it was associated with a high mortality rate. NTHi were the most common cause of invasive disease and showed high genetic diversity.

Increased biofilm formation by nontypeable Haemophilus influenzae isolates from patients with invasive disease or otitis media versus strains recovered from cases of respiratory infections.

Biofilm formation by nontypeable (NT) Haemophilus influenzae remains a controversial topic. Nevertheless, biofilm-like structures have been observed in the middle-ear mucosa of experimental chinchilla models of otitis media (OM). To date, there have been no studies of biofilm formation in large collections of clinical isolates. This study aimed to investigate the initial adhesion to a solid surface and biofilm formation by NT H. influenzae by comparing isolates from healthy carriers, those with noninvasive respiratory disease, and those with invasive respiratory disease. We used 352 isolates from patients with nonbacteremic community-acquired pneumonia (NB-CAP), chronic obstructive pulmonary disease (COPD), OM, and invasive disease and a group of healthy colonized children. We then determined the speed of initial adhesion to a solid surface by the BioFilm ring test and quantified biofilm formation by crystal violet staining. Isolates from different clinical sources displayed high levels of biofilm formation on a static solid support after growth for 24 h. We observed clear differences in initial attachment and biofilm formation depending on the pathology associated with NT H. influenzae isolation, with significantly increased biofilm formation for NT H. influenzae isolates collected from patients with invasive disease and OM compared with NT H. influenzae isolates from patients with NB-CAP or COPD and healthy colonized subjects. In all cases, biofilm structures were detached by proteinase K treatment, suggesting an important role for proteins in the initial adhesion and static biofilm formation measured by crystal violet staining.

Oropharyngeal colonization by nontypeable Haemophilus influenzae among healthy children attending day care centers.

Haemophilus influenzae colonizes the upper respiratory tract and can spread causing otitis and sinusitis. This work aimed to study the oropharyngeal carriage rate in healthy <5-year-old children attending day care centers in Oviedo, Spain in two consecutive years (January to March 2004-2005). The carriage rate was 42% (400/960) and highly variable among centers (range, 12% to 83%). Isolates were mainly identified as nontypeable H. influenzae (NTHi, 99%). Epidemiologically, 127 different genotypes were identified by PFGE with a minimum of two genotypes per center. One hundred fourteen children (12%) were included in both studies and none of them harbored the same strain over a period of time. The isolates only showed resistance to cotrimoxazol and ampicillin, presenting a shift in the level of ampicillin reduced susceptibility, showing a predominance of PBP3 mutations in 2004 and a predominance of ß-lactamase production in 2005. This study proved the great genetic variability of NTHi isolates that present similar genotypic patterns in both years with no long-term carriage of the same strain.

Incorporation of phosphorylcholine into the lipooligosaccharide of nontypeable Haemophilus influenzae does not correlate with the level of biofilm formation in vitro.

Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen that causes otitis media in children and community-acquired pneumonia or exacerbations of chronic obstructive pulmonary disease in adults. A large variety of studies suggest that biofilm formation by NTHi may be an important step in the pathogenesis of this bacterium. The objective of this report was to determine the relationship between the presence of phosphorylcholine in the lipooligosaccharide of NTHi and the level of biofilm formation. The study was performed on 111 NTHi clinical isolates collected from oropharyngeal samples of healthy children, middle ear fluid of children with otitis media, and sputum samples of patients with chronic obstructive pulmonary disease or community-acquired pneumonia. NTHi clinical isolates presented a large variation in the level of biofilm formation in a static assay and phosphorylcholine content. Isolates collected from the oropharynx and middle ear fluid of children tended to have more phosphorylcholine and made denser biofilms than isolates collected from sputum samples of patients with chronic obstructive pulmonary disease or community-acquired pneumonia. No correlation was observed between biofilm formation and the presence of phosphorylcholine in the lipooligosaccharide for either planktonic or biofilm growth. This lack of correlation was confirmed by abrogating phosphorylcholine incorporation into lipooligosaccharide through licA gene deletion, which had strain-specific effects on biofilm formation. Altogether, we present strong evidence to conclude that there is no correlation between biofilm formation in a static assay and the presence of phosphorylcholine in lipooligosaccharide in a large collection of clinical NTHi isolates collected from different groups of patients.

Molecular epidemiology of nontypeable Haemophilus influenzae causing community-acquired pneumonia in adults.

Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen which causes a variety of respiratory infections. The objectives of the study were to determine its antimicrobial susceptibility, to characterize the ß-lactam resistance, and to establish a genetic characterization of NTHi isolates. Ninety-five NTHi isolates were analyzed by pulsed field gel electrophoresis (PFGE) and multi locus sequence typing (MLST). Antimicrobial susceptibility was determined by microdilution, and the ftsI gene (encoding penicillin-binding protein 3, PBP3) was PCR amplified and sequenced. Thirty (31.6%) isolates were non-susceptible to ampicillin (MIC ≥ 2 mg/L), with 10 of them producing ß-lactamase type TEM-1 as a resistance mechanism. After ftsI sequencing, 39 (41.1%) isolates showed amino acid substitutions in PBP3, with Asn526 → Lys being the most common (69.2%). Eighty-four patients were successfully treated with amoxicillin/clavulanic acid, ceftriaxone and levofloxacin. Eight patients died due either to aspiration or complication of their comorbidities. In conclusion, NTHi causing CAP in adults shows high genetic diversity and is associated with a high rate of reduced susceptibility to ampicillin due to alterations in PBP3. The analysis of treatment and outcomes demonstrated that NTHi strains with mutations in the ftsI gene could be successfully treated with ceftriaxone or fluoroquinolones.

Infectious etiology of acute exacerbations in severe COPD patients.

OBJECTIVES: Since the new GOLD guidelines were implemented no data have been published about the etiology of acute exacerbations (AECOPD) in severe COPD patients with a different frequency of annual episodes. METHODS: One hundred and eleven COPD patients (FEV1 < 50%) were prospectively followed up for a year. Good-quality sputum samples recovered during AECOPD were processed, including quantitative culture and PCR detection of atypical bacteria. RESULTS: A total of 188 sputum samples were obtained from AECOPD episodes. Forty patients had a single episode, and 71 patients had ≥2. In 128 episodes a single pathogen was isolated, while 42 episodes were polymicrobial (≥2 pathogens). Overall, the most frequent pathogen isolated was Pseudomonas aeruginosa (n = 54), followed by Haemophilus influenzae (n = 37), Streptococcus pneumoniae (n = 31), Moraxella catarrhalis (n = 29) and Staphylococcus aureus (n = 12). P. aeruginosa was the most frequent in both groups of patients (35% and 27% in those with 1 and ≥2 AECOPD, respectively). H. influenzae was associated with patients with a single annual AECOPD (33% vs. 16%; P = 0.006), while Enterobacteriaceae were associated with frequent exacerbators (0% vs. 12%; P < 0.044). CONCLUSION: Overall, P. aeruginosa was the most frequent pathogen isolated from exacerbations. However, different bacterial etiology was observed depending on the number of annual episodes.

Comparison of restriction enzymes for pulsed-field gel electrophoresis typing of Moraxella catarrhalis.

NotI, the most prevalent restriction enzyme used for typing Moraxella catarrhalis, failed to digest genomic DNA from respiratory samples. An improved pulsed-field gel electrophoresis (PFGE) methodology determined SpeI as the best choice for typing this bacterial species, with a good restriction of clinical samples and a good clustering correlation with NotI.

Epithelial to mesenchymal transition and cancer stem cell phenotypes leading to liver metastasis are abrogated by the novel TGFß1-targeting peptides P17 and P144.

Colorectal cancer (CRC) frequently metastasizes to the liver, a phenomenon that involves the participation of transforming-growth-factor-ß(1) (TGFß(1)). Blockade of the protumorigenic effects elicited by TGFß(1) in advanced CRC could attenuate liver metastasis. We aimed in the present study to assess the antimetastatic effect of TGFß(1)-blocking peptides P17 and P144, and to study mechanisms responsible for this activity in a mouse model. Colon adenocarcinoma cells expressing luciferase were pretreated with TGFß(1) (Mc38-luc(TGFß1) cells), injected into the spleen of mice and monitored for tumor development. TGFß(1) increased primary tumor growth and liver metastasis, whereas systemic treatment of mice with either P17 or P144 significantly reduced tumor burden (p<0.01). In metastatic nodules, mitotic/apoptotic ratio, mesenchymal traits and angiogenesis (evaluated by CD-31, as well as circulating endothelial and progenitor cells) induced by TGFß(1) were consistently reduced following injection of peptides. In vitro experiments revealed a direct effect of TGFß(1) in Mc38 cells, which resulted in activation of Smad2, Smad3 and Smad1/5/8, and increased invasion and transendothelial migration, whereas blockade of TGFß(1)-signaling reverted these features. Because TGFß(1)-mediated epithelial-mesenchymal transition (EMT) has been suggested to induce a cancer stem cell (CSC) phenotype, we analyzed the ability of this cytokine to induce tumorsphere formation and the expression of CSC markers. In TGFß(1)-treated cells, tumorspheres were enriched in CD44 and SOX2, which were diminished in the presence of P17. Our data provide a preclinical rationale to evaluate P17 and P144 as potential therapeutic options for the treatment of metastatic CRC.

Genotypic and phenotypic diversity of the noncapsulated Haemophilus influenzae: adaptation and pathogenesis in the human airways

The human respiratory tract contains a highly adapted microbiota including commensal and opportunistic pathogens. Noncapsulated or nontypable Haemophilus influenzae (NTHi) is a human-restricted member of the normal airway microbiota in healthy carriers and an opportunistic pathogen in immunocompromised individuals. The duality of NTHi as a colonizer and as a symptomatic infectious agent is closely related to its adaptation to the host, which in turn greatly relies on the genetic plasticity of the bacterium and is facilitated by its condition as a natural competent. The variable genotype of NTHi accounts for its heterogeneous gene expression and variable phenotype, leading to differential host-pathogen interplay among isolates. Here we review our current knowledge of NTHi diversity in terms of genotype, gene expression, antigenic variation, and the phenotypes associated with colonization and pathogenesis. The potential benefits of NTHi diversity studies discussed herein include the unraveling of pathogenicity clues, the generation of tools to predict virulence from genomic data, and the exploitation of a unique natural system for the continuous monitoring of long-term bacterial evolution in human airways exposed to noxious agents. Finally, we highlight the challenge of monitoring both the pathogen and the host in longitudinal studies, and of applying comparative genomics to clarify the meaning of the vast NTHi genetic diversity and its translation to virulence phenotypes (AU)

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Does pet ownership in infancy lead to asthma or allergy at school age? Pooled analysis of individual participant data from 11 European birth cohorts.

OBJECTIVE: To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6-10 years. DESIGN: Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. EXPOSURE DEFINITION: Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. OUTCOME DEFINITION: Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6-10 years of age. DATA SYNTHESIS: Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models. RESULTS: We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with "no pets" (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I(2) = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with "no pets" (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I(2) = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to "no pets" resulted in an odds ratio of 1.04 (0.59 to 1.84) (I(2) = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens. CONCLUSIONS: Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6-10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.

Genotypic and phenotypic diversity of the noncapsulated Haemophilus influenzae: adaptation and pathogenesis in the human airways.

The human respiratory tract contains a highly adapted microbiota including commensal and opportunistic pathogens. Noncapsulated or nontypable Haemophilus influenzae (NTHi) is a human-restricted member of the normal airway microbiota in healthy carriers and an opportunistic pathogen in immunocompromised individuals. The duality of NTHi as a colonizer and as a symptomatic infectious agent is closely related to its adaptation to the host, which in turn greatly relies on the genetic plasticity of the bacterium and is facilitated by its condition as a natural competent. The variable genotype of NTHi accounts for its heterogeneous gene expression and variable phenotype, leading to differential host-pathogen interplay among isolates. Here we review our current knowledge of NTHi diversity in terms of genotype, gene expression, antigenic variation, and the phenotypes associated with colonization and pathogenesis. The potential benefits of NTHi diversity studies discussed herein include the unraveling of pathogenicity clues, the generation of tools to predict virulence from genomic data, and the exploitation of a unique natural system for the continuous monitoring of long-term bacterial evolution in human airways exposed to noxious agents. Finally, we highlight the challenge of monitoring both the pathogen and the host in longitudinal studies, and of applying comparative genomics to clarify the meaning of the vast NTHi genetic diversity and its translation to virulence phenotypes.

A retrospective study of edentulous patients rehabilitated according to the 'all-on-four' or the 'all-on-six' immediate function concept using flapless computer-guided implant surgery.

PURPOSE: To report the outcome of an implant therapy protocol using 4 or 6 implants supporting immediately loaded fixed prostheses following 3D software planning and flapless guided surgery. MATERIALS AND METHODS: A total of 30 patients (24 women, 6 men), mean age of 53 years (range 35-84 years) were treated with 195 immediately loaded implants (97 NobelSpeedy Groovy and 98 Brånemark MKIII Groovy) supporting 25 maxillary and 17 mandibular fixed full-arch acrylic prostheses and followed for 1 year. The Procera Software v1.6 and v2.0 was used to plan implant position and to obtain a surgical template for the guided flapless implant placement. To perform immediate loading, the implants had to be inserted with torque of at least 35 Ncm. Provisional prostheses were made before surgery using software planning and were placed in the same session as the implants. Definitive restorations were delivered 6-12 months after surgery. Outcome measures were failures of the prosthesis and of the implants, marginal bone level changes, complications, clinical time and patient satisfaction. RESULTS: Four patients with full edentulism and 26 with advanced periodontitis were enrolled in this study. A total of 195 implants were immediately loaded (128 implants were placed in the maxilla and 67 implants were placed in the mandible). Four implants out of 195 failed in three patients during the healing period: 2 in the maxilla (1 straight and 1 tilted), and 2 in the mandible (both of them tilted). Three of them were successfully replaced. One year after loading there were no dropouts and no failure of the definitive prosthesis occurred. In three cases, the surgical template fractured during surgery. In one patient, a new impression had to be taken to fit the provisional prosthesis onto the implants. Three patients were subjected to surgery and systemic antibiotics to treat apically infected implants. CONCLUSIONS: The 'all-on-four' and 'all-on-six' treatment protocol combined with computer-guided flapless implant surgery could be a viable and predictable treatment. Some complications occurred that were successfully treated. However, this technique could be sensitive to the experience of the surgeon and a learning curve is required.