Circulating YKL‐40 in myelofibrosis a potential novel biomarker of disease activity and the inflammatory state

Chronic myeloproliferative neoplasms (MPN), encompassing essential thrombocythaemia (ET), polycythaemia vera (PV) and myelofibrosis (PMF), are featured by a chronic inflammatory state which is pronounced in myelofibrosis The value of YKL‐40 as a biomarker of disease burden has been demonstrated in several different diseases, including cancer, diabetes mellitus and cardiovascular diseases. A state of chronic inflammation is shared by them all, YKL‐40 also being involved in the severity of chronic endothelial inflammation, which today is considered of crucial importance for the development of atherosclerosis. The MPNs being cancers with a heavy burden of cardiovascular diseases we hypothesised that circulating YKL‐40 might reflect the inflammatory process and potentially serve as a novel disease marker. Using ELISA, we measured YKL‐40 in 15 patients with ET, 16 patients with PV, 17 patients with PMF and 30 healthy controls. YKL‐40 was significantly elevated in PMF vs. control subjects, PMF levels median 43 ng/mL vs. controls median 28 ng/mL, P = 0.033. An increase from ET over PV may reflect the integrated impact of disease processes in MPNs.     

Lung function in Greenlandic and Danish children and adolescents

Respiratory morbidity in Inuit children is high. However, little is know regarding lung function measures in this population. The forced expiratory volumes in one second (FEV(1)) and forced vital capacity (FVC) in 888 Greenlandic Inuits (N=888) and Danes (N=477) aged 6-18 years were compared. Furthermore, associations between level of lung function and atopy and lifestyle factors were estimated in Greenlanders. The effect of height on FEV(1) and FVC was significantly different in Greenlanders and Danes, this difference in lung function increased with increasing height, and could not be explained by differences in age weight and BMI. Thus, Greenlanders taller than 130 cm had up to 300-400 ml higher FEV(1) and FVC compared with Danes of the same height. Among Greenlanders, those living in settlements had the highest levels of both FEV(1) and FVC. Greenlanders had elevated levels of FEV(1) and FVC compared with Danes. The Inuit having a shorter limb length in relation to trunk height may account for these differences. However, our finding that Greenlanders living in settlements had the highest lung function level also suggests a possible role of factors in the traditional Greenlandic lifestyle.     

Does cross-sex transmission increase the severity of polio infection? A study of multiple family cases

Previous studies have suggested that transmission of measles virus from the opposite sex increases the severity of infection; however, the role of gender in the transmission of other infections has not been examined. Multiple polio cases within a family usually occur simultaneously, and are therefore likely to be secondary to a common subclinical index case. The few clinical polio cases that appear much later than any other clinical case are likely to be tertiary cases. If cross-sex transmission increases the severity of infection then multiple polio cases would tend to affect the same sex, i.e. the opposite sex to that of the subclinical index case. In order to assess this phenomenon we identified 6345 records of individuals hospitalized with poliomyelitis in Copenhagen between 1919 and 1953. The severity and gender of suspected secondary and tertiary cases were analysed among all multiple household cases. Overall, 70% of the 133 sibling pairs having polio simultaneously were same-sex pairs, which differed significantly from the expected 52% (chi2 = 9.1; p < 0.01). Tertiary cases with exposure to the opposite sex were more likely to be paralytic than cases with exposure to the same sex [relative risk (RR) = 2.86 (95% confidence interval 1.08-7.58)1. In families with adult polio cases, possible tertiary cases were more common among fathers (7/24) than among mothers (1/35) [RR = 10.21 (1.34-77.72)]. We examined whether the excess of male polio cases was more pronounced in small families where the mother would play a relatively larger role in disease transmission and found that the male:female excess decreased with increasing birth order (p = 0.02) and family size (p = 0.09). The strong tendency towards same-sex pairs in 2-case families suggests that gender plays an important role in the severity of polio infection. Cross-sex transmission may increase the severity of polio and mothers may contribute to the higher prevalence of polio cases among boys.     

Programmable cells: interfacing natural and engineered gene networks

Novel cellular behaviors and characteristics can be obtained by coupling engineered gene networks to the cell's natural regulatory circuitry through appropriately designed input and output interfaces. Here, we demonstrate how an engineered genetic circuit can be used to construct cells that respond to biological signals in a predetermined and programmable fashion. We employ a modular design strategy to create Escherichia coli strains where a genetic toggle switch is interfaced with: (i) the SOS signaling pathway responding to DNA damage, and (ii) a transgenic quorum sensing signaling pathway from Vibrio fischeri. The genetic toggle switch endows these strains with binary response dynamics and an epigenetic inheritance that supports a persistent phenotypic alteration in response to transient signals. These features are exploited to engineer cells that form biofilms in response to DNA-damaging agents and cells that activate protein synthesis when the cell population reaches a critical density. Our work represents a step toward the development of "plug-and-play" genetic circuitry that can be used to create cells with programmable behaviors.     

Psychometric methods for diagnosing and monitoring minimal hepatic encephalopathy —current validation level and practical use

Metabolic Brain Disease - Hepatic encephalopathy (HE) is cerebral dysfunction caused by liver failure and inflicts 30-40% of patients with liver cirrhosis during their disease course. Clinically...     

Transient plasma cobalamin elevation in patients with pneumonia – two case reports

We report two cases of transient significantly elevated plasma cobalamin (B12) in geriatric patients acutely admitted with fever, increased C-reactive protein and X-ray verified pneumonia. Extensive diagnostic workup did not reveal kidney or liver disease, neither any signs of cancer. Furthermore, none of the patients had received therapeutic B12 supplementation prior to admission. In both cases, plasma B12 normalized at an out-patient control few months later. We were not able to identify the reason for the initial B12 elevation in any of the patients, since none of the usually recognized causes were evident. Since both patients had an infection and temporarily elevated B12, we suggest a possible inflammatory response or a vitamin B12 production by the infectious agents as the cause. Both suggestions, however, need further exploration.     

Cardiac computed tomography-verified right ventricular lead position and outcomes in cardiac resynchronization therapy

Journal of Interventional Cardiac Electrophysiology - To evaluate the association between different right ventricular (RV) lead positions as assessed by cardiac computed tomography (CT) and...