Cardiobacterium hominis endocarditis incidentally diagnosed following an aortic valve replacement surgery.

Background: Cardiobacterum hominis (C. hominis) is the part of the HACEK group (Haemophilus spp, Actinobacillus spp, C. hominis, Eikenella, and Kingella spp) that accounts for the majority of the Gram-negative infective endocarditis cases. Historically, the fastidious characteristics of these microorganisms proved challenging to many clinicians. Advances in microbiological identification of culture-negative endocarditis; however, may be the reason for the rising incidence of these infections. Here, we report an incidentally diagnosed C. hominis endocarditis following an aortic valve replacement. Case report: A healthy 54-year-old gentleman presented after several months of generalized weakness and exertional intolerance. He was found to have a bicuspid aortic valve with regurgitation and underwent aortic valve replacement surgery. Intraoperatively, the patient was found to have a large perforation of the fused leaflet associated with abnormal pink tissue in the aortic valve area. The aortic valve tissue was cultured. Gram-negative rods were isolated 48 h later and were ultimately identified as C. hominis. He was successfully treated with 6 weeks of intravenous ceftriaxone with sterile blood cultures throughout the hospital stay. In retrospect, the patient's valve failure was likely secondary to subacute endocarditis from C. hominis complicated by leaflet perforation. Conclusion: C. hominis is a rare cause of infective endocarditis with an excellent prognosis when timely diagnosed and managed. By reporting this case, we wish to raise awareness of potential asymptomatic infection, particularly amongst patients with underlying native valve abnormalities, new leaflet perforation, and valve insufficiency.

Imaging-based predictors of permanent pacemaker implantation after transcatheter aortic valve replacement.

BACKGROUND: Cardiac conduction abnormalities requiring permanent pacemaker (PPM) implantation are major complications of transcatheter aortic valve replacement (TAVR). We aimed to investigate whether the relationship between prosthetic valve size and cardiac-gated computed tomography (CT)-based aortic root complex measurements can aid in recognizing patients at risk for PPM implantation post-TAVR. METHODS: We included 83 of 114 consecutive patients who underwent TAVR with the Edwards Sapien valve (Edwards Lifesciences, Irving, CA, USA) at our institution. We excluded patients with preexisting PPM, patients who required conversion to an open surgical procedure, and patients without CT data. We assessed the significance of various potential predictors of PPM placement post-TAVR. RESULTS: Following TAVR, eight patients (9.6%) required PPM. Prosthetic valve to sinus of Valsalva (SOV) index was significantly higher in those patients requiring a PPM post-TAVR (84.1 ± 9.3 vs 76.8 ± 7.1, P  =  0.009). CONCLUSIONS: The prosthetic valve size to diameter of SOV index was identified as a novel predictor of PPM implantation after TAVR.

Erratum: SWELL1 is a regulator of adipocyte size, insulin signalling and glucose homeostasis.

This corrects the article DOI: 10.1038/ncb3514.

SWELL1 is a regulator of adipocyte size, insulin signalling and glucose homeostasis.

Adipocytes undergo considerable volumetric expansion in the setting of obesity. It has been proposed that such marked increases in adipocyte size may be sensed via adipocyte-autonomous mechanisms to mediate size-dependent intracellular signalling. Here, we show that SWELL1 (LRRC8a), a member of the Leucine-Rich Repeat Containing protein family, is an essential component of a volume-sensitive ion channel (VRAC) in adipocytes. We find that SWELL1-mediated VRAC is augmented in hypertrophic murine and human adipocytes in the setting of obesity. SWELL1 regulates adipocyte insulin-PI3K-AKT2-GLUT4 signalling, glucose uptake and lipid content via SWELL1 C-terminal leucine-rich repeat domain interactions with GRB2/Cav1. Silencing GRB2 in SWELL1 KO adipocytes rescues insulin-pAKT2 signalling. In vivo, shRNA-mediated SWELL1 knockdown and adipose-targeted SWELL1 knockout reduce adiposity and adipocyte size in obese mice while impairing systemic glycaemia and insulin sensitivity. These studies identify SWELL1 as a cell-autonomous sensor of adipocyte size that regulates adipocyte growth, insulin sensitivity and glucose tolerance.

Lack of association between the Tlr4 (Lpsd/Lpsd) genotype and increased susceptibility to Escherichia coli bladder infections in female C3H/HeJ mice.

UNLABELLED: Toll-like receptor 4 is thought to have a primary role in host defense against Escherichia coli bladder colonization, based on mouse models of urinary tract infection using C3H/HeJ female mice. This strain carries a point mutation in the Tlr4 gene, which renders the mice unresponsive to lipopolysaccharide (LPS) and thus limits the bladder inflammatory response and infection resolution. The importance of Tlr4 as the sole genetic determinant of resistance or susceptibility can be questioned, however, by the observation that C3H/HeOuJ female mice with a functional Tlr4 do not effectively resolve E. coli bladder infections. The present study further examined this inconsistency by investigating the association of Tlr4 Lps(d) and Lps(n) alleles with bladder infection susceptibility by using genetic crosses of C3H/HeJ mice with Tlr4 (Lps(n)/Lps(n)) or (Lps(n)/Lps(d)) mice. Heterozygous offspring of C3H/HeJ (Lps(d)/Lps(d)) × BALB/cAnN (Lps(n)/Lps(n)) mice successfully resolved bladder infections induced by a uropathogenic E. coli strain, while heterozygous mice from a C3H/HeJ (Lps(d)/Lps(d)) × C3H/HeOuJ (Lps(n)/Lps(n)) cross had severe infections. A backcross of C3H/HeJ (Lps(d)/Lps(d)) with (BALB/cAnN × C3H/HeJ)F(1) (Lps(n)/Lps(d)) produced mice that were either resistant or susceptible to E. coli bladder infections and had Lps(d)/Lps(d) or Lps(n)/Lps(d) Tlr4 genotypes. The Lps(d)/Lps(d) or Lps(n)/Lps(d) genotypes were present in individual mice with unresolved bladder infections, and the Lps(d)/Lps(d) genotype was found in infection-resistant mice. These results indicate that at least one gene other than Tlr4 strongly influences susceptibility to E. coli bladder infections in C3H/HeJ mice. IMPORTANCE: We have previously demonstrated that mouse strains with either a functional or nonfunctional Tlr4 were not able to resolve induced Escherichia coli bladder infections and that a chromosomal site distinct from Tlr4 was associated with an inability to resolve bladder infections in C3H/HeJ mice. The present study has further investigated the relevance of Tlr4 in bladder infection resolution by defining the Tlr4 alleles present in offspring of genetic crosses of C3H/HeJ mice with infection-resistant and -susceptible inbred strains. The results of these experiments showed that mice with a normal Tlr4 on different genetic backgrounds were not able to clear E. coli bladder infections and that animals with a defective Tlr4 could successfully resolve infections. These results strongly imply the presence of a gene other than in Tlr4 as an important genetic determinant of infection resistance/susceptibility in C3H/HeJ and other inbred mouse strains used in mouse models of infectious diseases.

Tolerance to noninherited maternal MHC antigens in mice.

The phenomenon of tolerance to noninherited maternal Ags (NIMA) is poorly understood. To analyze the NIMA effect C57BL/6 (H-2(b/b)) males were mated with B6D2F(1) (H-2(b/d)) females, whereby 50% of the offspring are H-2(b/b) mice that have been exposed to maternal H-2(d) alloantigens. Controls were H-2(b/b) offspring of C57BL/6 mothers, either inbred C57BL/6 mice or F(1) backcross mice from breedings with H-2(b/d) fathers. We found that 57% of the H-2(b/b) offspring of semiallogeneic (H-2(b/d)) mothers accepted fully allogeneic DBA/2 (H-2(d/d)) heart grafts for >180 days, while similar transplants were all rejected by day 11 in controls (p < 0.0004). Foster nursing studies showed that both oral and in utero exposure to NIMA are required for this tolerogenic effect. An effect of NIMA was also found to extend the survival of skin grafts from a semiallogeneic donor (p < 0.02). Pretransplant analysis of splenocytes showed a 40-90% reduction of IL-2-, IL-5-, and IFN-gamma-producing T cells responding to H-2(d)-expressing APC in NIMA(d)-exposed vs control mice. Injection of pregnant BALB/c-dm2 (H-2L(d)-negative) female mice i.v. with H-2L(d)(61-80) peptide profoundly suppressed the offspring's indirect pathway alloreactive CD4(+) T cell response to H-2L(d). These results suggest that the natural exposure of the fetus and newborn to maternal cells and/or soluble MHC Ags suppresses NIMA-allospecific T cells of the offspring, predisposing to organ transplant tolerance in adult mice.