Nontypeable Haemophilus influenzae P5 Binds Human C4b-Binding Protein, Promoting Serum Resistance.

Nontypeable Haemophilus influenzae (NTHi) is a Gram-negative human pathogen that causes infections mainly in the upper and lower respiratory tract. The bacterium is associated with bronchitis and exacerbations in patients suffering from chronic obstructive pulmonary disease and frequently causes acute otitis media in preschool children. We have previously demonstrated that the binding of C4b binding protein (C4BP) is important for NTHi complement evasion. In this study, we identified outer membrane protein 5 (P5) of NTHi as a novel ligand of C4BP. Importantly, we observed significantly lower C4BP binding and decreased serum resistance in P5-deficient NTHi mutants. Surface expression of recombinant P5 on Escherichia coli conferred C4BP binding and consequently increased serum resistance. Moreover, P5 expression was positively correlated with C4BP binding in a series of clinical isolates. We revealed higher levels of P5 surface expression and consequently more C4BP binding in isolates from the lower respiratory tract of chronic obstructive pulmonary disease patients and tonsil specimens compared with isolates from the upper respiratory tract and the bloodstream (invasive strains). Our results highlight P5 as an important protein for protecting NTHi against complement-mediated killing.

Bacteremia with ESBL-producing Enterobacterales is associated with IgG antibodies reacting with CTX-M-15 and/or CTX-M-27.

OBJECTIVES: The adaptive humoral immune response following clinical infection with extended spectrum beta-lactamase (ESBL)-producing Enterobacterales (EPE) has not been thoroughly investigated. The aim of this study was to investigate the presence of anti-CTX-M-15 and/or anti-CTX-M-27 IgG antibodies in bacteremia patients diagnosed with EPE compared to a control group consisting of patients suffering from bacteremia with third generation cephalosporin-susceptible Escherichia coli (3GCSE). METHODS: Patientswith EPE (n = 59) or 3GCSE (n = 42) bacteremia were recruited in this case control study in the Skåne County (South of Sweden). Sera were collected 1-26 months after bacteremia. Enzyme-linked immunosorbent assay (ELISA) was used for detection of specific IgG antibodies directed against recombinant beta-lactamases CTX-M-15 and CTX-M-27. The beta-lactamase resistance genes of the corresponding EPE blood isolates were determined by DNA sequencing. RESULTS: The majority (n = 47; 80 %) of the 59 EPE blood isolates carried blaCTX-M-15 or blaCTX-M-27 genes. IgG antibodies reacting to the corresponding CTX-M enzyme was seen in 28 % (13/47) of patients suffering from EPE-bacteremia, while antibodies were detected in only 9.5 % (4/42) of patients with 3GCSE (p = 0.03). Patients with EPE had a statistically significantly higher median Charlson comorbidity index and prevalence of renal disease (p = 0.01), compared to the 3GCSE control group. CONCLUSION: This study implies that EPE bacteremia can trigger production of IgG antibodies targeting ESBL. Further investigations are required to determine the functional role of anti-ESBL antibodies against EPE bacteremia.

The Laminin Interactome: A Multifactorial Laminin-Binding Strategy by Nontypeable Haemophilus influenzae for Effective Adherence and Colonization.

Laminin is a well-defined component of the airway basement membrane (BM). Efficient binding of laminin via multiple interactions is important for nontypeable Haemophilus influenzae (NTHi) colonization in the airway mucosa. In this study, we identified elongation factor thermo-unstable (EF-Tu), l-lactate dehydrogenase (LDH), protein D (PD), and peptidoglycan-associated lipoprotein P6 as novel laminin-binding proteins (Lbps) of NTHi. In parallel with other well-studied Lbps (protein 4 [P4], protein E [PE], protein F [PF], and Haemophilus adhesion and penetration protein [Hap]), EF-Tu, LDH, PD, and P6 exhibited interactions with laminin, and mediated NTHi laminin-dependent adherence to pulmonary epithelial cell lines. More importantly, the NTHi laminin interactome consisting of the well-studied and novel Lbps recognized laminin LG domains from the subunit α chains of laminin-111 and -332, the latter isoform of which is the main laminin in the airway BM. The NTHi interactome mainly targeted multiple heparin-binding domains of laminin. In conclusion, the NTHi interactome exhibited a high plasticity of interactions with different laminin isoforms via multiple heparin-binding sites.

Trigger factors in takotsubo syndrome - A systematic review of case reports.

INTRODUCTION: Takotsubo syndrome is an acute heart failure syndrome often preceded by a trigger factor of physical or emotional origin, although the proportion is unclear. The aim of the present study was to determine how common different trigger factors are in takotsubo syndrome divided by sex and age in women. MATERIAL AND METHODS: The study consisted of a systematic review of all available case reports in PubMed and Web of Science up to March 2018. Trigger factors were categorized into physical and emotional trigger factors. RESULTS: Males had to a higher degree experienced a trigger factor (92.6%) compared to females (81.9%, p < .001). Physical trigger factors were most common (67.3%). Males had to a higher degree experienced a physical trigger factor (85.7%) compared to females (63.5%, p < .001). Females ≤50 years of age had to a higher degree experienced a trigger factor (90.8%) compared to females >50 years of age (79.2%, p < .001). Additionally, females ≤50 years of age had to a higher degree experienced a physical trigger factor (75.6%) compared to females >50 years of age (59.3%, p < .01). CONCLUSION: A physical trigger factor is more common than an emotional trigger factor in takotsubo syndrome. Physical triggers includes drugs, surgery and central nervous system conditions. Furthermore, females ≤50 years of age and males more often have an evident trigger factor and it is more often physical, compared to the most common patient, a female >50 years of age.

A Cost-utility Analysis of Calcipotriol/Betamethasone Dipropionate Aerosol Foam versus Ointment for the Topical Treatment of Psoriasis Vulgaris in Sweden.

Psoriasis is a chronic inflammatory disorder that imposes a substantial economic burden. We conducted a cost-utility analysis from a Swedish healthcare payers perspective using a decision-tree model with a 12-week time horizon. Patients with psoriasis vulgaris could have two 4-week cycles of topical treatment with calcipotriol 50 µg/g and betamethasone 0.5 mg/g as dipropionate (Cal/BD) foam or Cal/BD ointment before progressing to phototherapy/methotrexate. In the base-case analysis, Cal/BD foam dominated over Cal/BD ointment. The increased efficacy of Cal/BD foam resulted in fewer consultations and a decreased risk of progressing to phototherapy/methotrexate. Although Cal/BD foam costs more than Cal/BD ointment, this was offset by lower costs for phototherapy/methotrexate or consultation visits. Sensitivity analyses revealed that the base-case net monetary benefit was robust to plausible variations in key parameters. In conclusion, Cal/BD foam was predicted to be more cost-effective than Cal/BD ointment in the treatment of psoriasis vulgaris.

Titanium granules pre-treated with hydrogen peroxide inhibit growth of bacteria associated with post-operative infections in spine surgery.

PURPOSE: Post-operative infections are relatively common after posterior spine surgery, and there are several observations reflecting different infection complications related to various metals implanted. Here, we selected an array of different bacterial species that are often found in infections associated with orthopaedic implants and tested for inhibition by hydrogen peroxide-treated titanium (Ti-peroxy). METHODS: To study the possibility of using Ti-peroxy as an antimicrobial prophylaxis, we developed a protocol for standardized susceptibility testing of bacteria. RESULTS: Importantly, we found that the resulting Ti-peroxy was highly antimicrobial against all aerobic species tested, among others, Staphylococcus aureus and Pseudomonas aeruginosa. Proteus mirabilis was slightly more resistant than, for example, Klebsiella pneumoniae and enterococci. In contrast, anaerobic bacteria Cutibacterium acnes and Parvimonas micra were equally susceptible compared to staphylococci. CONCLUSIONS: Our findings suggest that the Ti-peroxy is a promising perioperative antimicrobial strategy that may be highly effective for prevention of post-operative infections. We therefore suggest application of hydrogen peroxide to implants prior to implantation. These slides can be retrieved under Electronic supplementary material.

Lack of genetic susceptibility in takotsubo cardiomyopathy: a case-control study.

BACKGROUND: Takotsubo cardiomyopathy (TCM), also known as "broken heart syndrome", is a type of heart failure characterized by transient ventricular dysfunction in the absence of obstructive coronary lesions. Although associated with increased levels of catecholamines, pathophysiological mechanisms are unknown. Relapses and family heritability indicate a genetic predisposition. Several small studies have investigated associations between three different loci; the ß1-adrenic receptor (ADRB1), G-protein-coupled receptor kinase 5 (GRK5), Bcl-associated athanogene 3 (BAG3) and TCM but no consensus has been reached. METHODS: Participants were recruited using the Swedish Coronary Angiography and Angioplasty Register (SCAAR). TCM patients without coronary artery disease (CAD)(n = 258) were identified and age- and sex-matched subjects with (n = 164) and without (n = 243) CAD were selected as controls. DNA was isolated from saliva and genotyped for candidate single nucleotide polymorphisms in the ADRB1, GRK5 and BAG3 genes. Allele frequencies and Odds Ratios (OR) with 95% Confidence Intervals (CI) for the investigated polymorphisms were compared, respectively calculated for TCM patients and controls. RESULTS: There were no differences in allele frequencies between TCM patients and controls. OR (CI) for TCM patients having at least one minor allele using controls as reference were 1.07 (0.75-1.55) for ADRB1, 0.45 (0.11-1.85) for GRK5 and 1.27 (0.74-2.19) for BAG3. CONCLUSION: By genotyping a large takotsubo cohort, we demonstrate a lack of association between candidate SNPs in the ADRB1, GRK5 and BAG3 genes, earlier suggested to contribute to TCM. Our result indicates a need to expand the search for new genetic candidates contributing to TCM.