Serum markers of infections in patients with primary biliary cirrhosis: evidence of infection burden

Background

Currently not much is known regarding the environmental factors involved in primary biliary cirrhosis (PBC). It is even more unclear which factors may determine the subgroup (i.e., AMA status) of patients with PBC. We thus tested AMA + and AMA − PBC patients' sera for antibodies (Abs) against multiple infectious agents.

Methods

Sera from 69 patients with PBC (49 AMA + and 20 AMA −) and 100 matched controls were screened for IgG-Abs against Toxoplasma gondii, Helicobacter pylori, Epstein–Barr virus (EBV), cytomegalovirus (CMV), hepatitis B, and hepatitis C utilizing the BioPlex 2200 and ELISA kits (Bio-Rad Laboratories, USA).

Results

The prevalence of four anti-infectious agents Abs was significantly elevated among PBC patients when compared with controls, namely anti-T. gondii (ATxA; 71% vs. 40%, p < 0.0001), EBV early antigen (EA; 44% vs. 12%, p < 0.0001), H. pylori (54% vs. 31%, p < 0.01), and CMV (90% vs. 75%, p < 0.05) Abs, respectively. The co-occurrence of these four anti-infectious agents Abs was highly common in PBC, whereas this infection burden was rare in healthy subjects (20% vs. 3% respectively, p < 0.0001). Furthermore, specific infections interactions possibly increasing PBC risk were noted as well. Seropositivity of ATxA was inversely associated with cirrhosis among PBC patients (p < 0.05). Finally, no differences were observed between AMA − sera and their AMA + counterparts with regard to seroprevalence of any of the investigated infectious agents.

Conclusions

We note the association of ATxA and PBC, with the possibility of a milder disease manifestation. We also suggest that multiple exposures to infectious agents may contribute to PBC risk.     

A Swordless Knight: Epidemiology and Molecular Characteristics of the blaKPC-Negative Sequence Type 258 Klebsiella pneumoniae Clone

In June 2010, a bla(KPC)-negative, ertapenem-resistant ST-258 Klebsiella pneumoniae strain was isolated from a patient in the Laniado Medical Center (LMC). Our aims were (i) to describe its molecular characteristics and resistance mechanisms and (ii) to assess whether the bla(KPC)-negative ST-258 K. pneumoniae clone spreads as efficiently as its KPC-producing isogenic strain. In a prospective study, surveillance of all ertapenem-resistant, carbapenemase-negative K. pneumoniae (ERCNKP) isolates was conducted from June 2010 to May 2011 at LMC (314 beds) and from July 2008 to December 2010 at the Tel Aviv Sourasky Medical Center (TASMC) (1,200 beds). Molecular typing was done by arbitrarily primed PCR, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST). A total of 8 of 42 (19%) ERCNKP isolates in LMC and 1 of 32 (3.1%) in TASMC belonged to the ST-258 clone. These strains carried the bla(CTX-M-2) or the bla(CTX-M-25) extended-spectrum β-lactamase (ESBL) gene. Sequencing of the ompK genes showed a frameshift mutation in the ompK35 gene. The fate of the bla(KPC)-carrying plasmid, pKpQIL, was determined by S1 analysis and by PCR of the Tn4401 transposon, repA, and the truncated bla(OXA-9). Plasmid analysis of the ERCNKP ST-258 isolates showed variability in plasmid composition and absence of the Tn4401 transposon and the pKpQIL plasmid. In addition, the ST-258 clone was identified in 35/35 (100%) of KPC-producing K. pneumoniae isolates but in none of 62 ertapenem-susceptible K. pneumoniae isolates collected in the two centers. Our results suggest that ERCNKP ST-258 evolved by loss of the bla(KPC)-carrying plasmid pKpQIL. ERCNKP ST-258 appears to have low epidemic potential.     

Polyunsaturated fatty acids as putative cognitive enhancers

Polyunsaturated essential fatty acids (PUFAs) play a pivotal role in mediating cognitive, learning, and memory functions. We propose that PUFAs directly affect the neuronal membrane. PUFAs serve to stabilize and protect the structure and functions of the neuronal membrane. PUFAs exert many effects on the brain with respect to physiology, brain biochemistry, and disorders of the central nervous system. Many of these functions have effects at the cognitive level. This summary demonstrates that a deficiency in brain PUFAs will lead to cognitive deficits, while supplementation of PUFAs can rehabilitate cognitive deficits, as manifested in attention deficit hyperactivity disorder, stress/anxiety, and aging.     

The Pathogenesis of Neural Injury in Animal Models of the Antiphospholipid Syndrome

Circulating antiphospholipid antibodies (aPL) are associated with central nervous system dysfunction in antiphospholipid syndrome (APS) patients and in a mouse model of APS. We propose a logical pathway of how experimental APS (eAPS) causes brain dysfunction: binding of the antibodies to the brain endothelium evoking microthrombosis, endothelial dysfunction, and IgG leakage through the blood–brain barrier (BBB), then secondary inflammatory cell spread around blood vessels and production of cytokines by these inflammatory cells leading to further disruption of the BBB. The diffuse brain endothelial dysfunction would result in extravasation of serum proteins including APS IgG and activated thrombin, which may induce the behavioral changes observed in the APS mice. We have collected data from the mouse eAPS model which supports this hypothesis. Elucidating the mechanism of the pathogenicity of aPL in vitro and in vivo will serve as a much needed basis for developing new therapeutic modalities in this important disorder.     

Susceptibility variants for obesity and colorectal cancer risk: the multiethnic cohort and PAGE studies

Obesity is a leading contributor to colorectal cancer risk. We investigated whether the risk variants identified in genome-wide association studies of body mass index (BMI) and waist size are associated with colorectal cancer risk, independently of the effect of obesity phenotype due to a shared etiology. Twenty-four single nucleotide polymorphisms (SNPs) in 15 loci (BDNF, FAIM2, FTO, GNPDA2, KCTD15, LYPLAL1, MC4R, MSRA, MTCH2, NEGR1, NRXN3, SEC16B, SH2B1, TFAP2B and TMEM18) were genotyped in a case-control study of 2,033 colorectal cancer cases and 9,640 controls nested within the multiethnic cohort study, as part of the population architecture using genomics and epidemiology consortium. Risk alleles for two obesity SNPs were associated with colorectal cancer risk--KCTD15 rs29941 [odds ratio (OR) for C allele = 0.90, 95% confidence interval (CI) 0.83-0.98; p = 0.01] and MC4R rs17782313 (OR for C allele = 1.12, 95% CI 1.02-1.22; p = 0.02). These associations were independent of the effect of BMI. However, none of the results remained significant after adjustment for multiple comparisons. No heterogeneity was observed across race/ethnic groups. Our findings suggest that the obesity risk variants are not likely to affect the risk of colorectal cancer substantially.     

The Surgical Treatment of Traumatic Hematoma of the Auricle

BACKGROUND: The auricular hematoma occurs secondary to trauma and can present a therapeutic dilemma for clinicians. Early intervention can be limited to simple incision and drainage. Delay in treatment may allow the growth of ectopic fibroneocartilage derived from the damaged perichondrium. Removal of this abnormal tissue is imperative to avoid permanent ear deformity. OBJECTIVE: Surgical intervention was utilized to treat auricular hematomas in two teenage boys. METHODS: The auricular hematomas were treated by raising a cutaneous flap over the injury site. The clot and serosanguinous fluid were drained and, because the injuries were 1 month old, the developing plate of fibroneocartilage and associated perichondrium was extirpated. The exposed cartilage was fenestrated prior to repairing the cutaneous flap. RESULTS: Both auricles healed without evidence of fibrosis or distortion. CONCLUSION: Appropriate surgical intervention can avoid the cosmetic deformity associated with an auricular hematoma (ie, cauliflower ear).     

Limited English Proficiency Is a Barrier to Receipt of Advice about Physical Activity and Diet among Hispanics with Chronic Diseases in the United States

The prevalence of obesity, diabetes, and cardiovascular disease is reaching epidemic proportions among Hispanics in the United States. Health care providers play an important role in motivating patients to make healthful lifestyle changes to reduce the burden of such conditions. Data from the US 2000 National Health Interview Survey was analyzed to determine differences in report of physician-provided physical activity and/or dietary advice by level of English proficiency among obese Hispanics or those who reported having diabetes or cardiovascular disease and who contacted a physician during the past year (n=1,186). Only one third of the sample reported receiving advice to increase their physical activity or to improve their dietary habits; one fifth reported receipt of advice about both. English-proficient Hispanics were about 50% more likely to report receiving advice on physical activity (adjusted odd ratio [AOR]=1.5; 95% confidence interval [CI]: 1.1 to 2.1), diet (AOR=1.5; 95% CI: 1.1 to 2.2) or both (AOR=1.6; 95% CI: 1.1 to 2.3), as compared with limited English-proficient Hispanics, after controlling for health insurance coverage and number of visits to a physician during the last year. Sex, age, region of residence, level of education, annual family income, and smoking status were not significantly associated with receiving physical activity and/or dietary advice. In order to address racial health disparities, and lower the burden of chronic illness, culturally sensitive strategies must be implemented to enhance delivery of effective health-promotion messages by physicians, particularly among at-risk communities.