Iron accumulation in the choroid plexus,ependymal cells and CNS parenchyma in a rat strain with low‐grade haemolysis of fragile macrocytic red blood cells

Iron accumulation in the CNS is associated with many neurological diseases via amplification of inflammation and neurodegeneration. However, experimental studies on iron overload are challenging, since rodents hardly accumulate brain iron in contrast to humans. Here, we studied LEWzizi rats, which present with elevated CNS iron loads, aiming to characterise choroid plexus, ependymal, CSF and CNS parenchymal iron loads in conjunction with altered blood iron parameters and, thus, signifying non‐classical entry sites for iron into the CNS. Non‐haem iron in formalin‐fixed paraffin‐embedded tissue was detected via DAB‐enhanced Turnbull Blue stainings. CSF iron levels were determined via atomic absorption spectroscopy. Ferroportin and aquaporin‐1 expression was visualised using immunohistochemistry. The analysis of red blood cell indices and serum/plasma parameters was based on automated measurements; the fragility of red blood cells was manually determined by the osmotic challenge. Compared with wild‐type animals, LEWzizi rats showed strongly increased iron accumulation in choroid plexus epithelial cells as well as in ependymal cells of the ventricle lining. Concurrently, red blood cell macrocytosis, low‐grade haemolysis and significant haemoglobin liberation from red blood cells were apparent in the peripheral blood of LEWzizi rats. Interestingly, elevated iron accumulation was also evident in kidney proximal tubules, which share similarities with the blood–CSF barrier. Our data underscore the importance of iron gateways into the CNS other than the classical route across microvessels in the CNS parenchyma. Our findings of pronounced choroid plexus iron overload in conjunction with peripheral iron overload and increased RBC fragility in LEWzizi rats may be seminal for future studies of human diseases, in which similar constellations are found.     

Multidrug-resistant bacteria in geriatric clinics,nursing homes,and ambulant care – Prevalence and risk factors

Colonization/infection with multidrug-resistant bacteria (MDRB) such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae, is an increasing problem not only in hospitals but also in long-term care facilities. The aim of this study was to determine the prevalence as well as the risk factors of colonization/infection with MRSA, VRE, and ESBL producing Enterobacteriaceae in geriatric clinics, nursing homes, and ambulant care in Frankfurt am Main, Germany. 288 patients from 2 geriatric clinics (n = 46), 8 nursing homes (n = 178), and 2 ambulant care facilities (n = 64) as well as 64 staff members were screened for MDRB in the time period from October 2006 to May 2007. 58 patients (20.1%) and 4 staff members (6.2%) were colonized with MDRB. Among patients, 27 (9.4%) were colonized with MRSA, 11 (3.8%) were screened positive for VRE, and 25 (8.7%) were found to be colonized with ESBL producing Enterobacteriaceae. Prevalence of MDRB in geriatric clinics, nursing homes, and ambulant care facilities were 32.6%, 18.5%, and 15.6%, respectively. Significant risk factors for MDRB were immobility (OR: 2.7, 95% CI: 1.5–4.9; p = 0.002), urinary catheter (OR: 3.1, 95% CI: 1.7–5.9; p < 0.001), former hospitalization (OR: 2.1, 95% CI: 1.1–4.0; p = 0.033), and wounds/decubiti (OR: 2.3, 95% CI: 1.5–4.9; p = 0.03). Finally, the high level of MDRB in geriatric clinics, nursing homes, and ambulant care points to the importance of these institutions as a reservoir for dissemination.     

Multisite Near Infrared Spectroscopy During Cardiopulmonary Bypass in Pediatric Patients

Multisite near infrared spectroscopy (NIRS) monitoring during pediatric cardiopulmonary bypass (CPB) has not been extensively validated. Although it might be rational to explore regional tissue saturation at different body sites (namely brain, kidney, upper body, lower body), conflicting results are currently provided by experience in children. The aim of our study was to evaluate absolute values of multisite NIRS saturation during CPB in a cohort of infants undergoing pediatric cardiac surgery to describe average differences between cerebral, renal, upper body (arm), and lower body (thigh) regional saturation. Furthermore, the correlation between cerebral NIRS and cardiac index (CI) at CPB weaning was evaluated. Twenty‐five infants were enrolled: their median weight, age, and body surface area were 3.9 (3.3–6) kg, 111 (47–203) days, and 0.24 (0.22–0.33) m², respectively. Median Aristotle score was 8 (6–10), and vasoactive inotropic score at CPB weaning was 16 (14–25). A total of 17 430 data points were recorded by each sensor: two‐way ANOVA showed that time (P < 0.0001) and site (P = 0.0001) significantly affected variations of NIRS values: however, if cerebral NIRS values are excluded, sensor site is no more significant (P = 0.184 in the no circulatory arrest [noCA] group and P = 0.42 in the circulatory arrest [CA] group). Analysis of NIRS saturation changes over time showed that, at all sites, average NIRS values increased after CPB start, even if the increase of cerebral saturation was less intense than other sites (P < 0.0001). Detailed analysis of interaction between site of NIRS measurement and time point showed that cerebral NIRS (ranging from 65 to 75%) was always significantly lower than that of other channels (P < 0.0001) that tended to be in the range of oversaturation (80–90%), especially during the CPB phase. Average cerebral NIRS values of patients who did not undergo circulatory arrest (CA) during CPB, 10 min after CPB weaning, were associated with average CI values with a significant correlation (r = 0.7, P = 0.003). In conclusion, during CPB, cerebral NIRS values are expected to remain constantly lower than somatic sensors, which instead tend to show similar elevated saturations, regardless of their position. Based on these results, positioning of noncerebral NIRS sensors during CPB without CA may be questioned.     

Alpha,beta hybrid peptides: a polypeptide helix with a central segment containing two consecutive beta-amino acid residues

Conformational studies on the synthetic 11-aa peptide t-butoxycarbonyl (Boc)-Val-Ala-Phe-alpha-aminoisobutyric acid (Aib)-(R)-beta3-homovaline (betaVal)-(S)-beta3-homophenylalanine (betaPhe)-Aib-Val-Ala-Phe-Aib-methyl ester (OMe) (peptide 1; betaVal and betaPhe are beta amino acids generated by homologation of the corresponding l-residues) establish that insertion of two consecutive beta residues into a polypeptide helix can be accomplished without significant structural distortion. Crystal-structure analysis reveals a continuous helical conformation encompassing the segment of residues 2-10 of peptide 1. At the site of insertion of the betabeta segment, helical hydrogen-bonded rings are expanded. A C15 hydrogen bond for the alphabetabeta segment and two C14 hydrogen bonds for the alphaalphabeta or betaalphaalpha segments have been characterized. The following conformational angles were determined from the crystal structure for the beta residues: betaVal-5 (= -126 degrees, = 76 degrees, and psi = -124) and betaPhe-6 (=-88 degrees, = 80 degrees, and psi =-118). The N terminus of the peptide is partially unfolded in crystals. The 500-MHz 1H-NMR studies establish a continuous helix over the entire length of the peptide in CDCl3 solution, as evidenced by diagnostic nuclear Overhauser effects. The presence of seven intramolecular hydrogen bonds is also established by using solvent dependence of NH chemical shifts.     

Label-free surface-enhanced Raman spectroscopy for detection of colorectal cancer and precursor lesions using blood plasma

Fecal based tests have limited diagnostic values in detecting adenomatous polyps, the precursor lesions to colorectal cancer (CRC). Surface enhanced Raman spectroscopy (SERS) using silver nanoparticles as substrate is a multiplexed analytical technique capable of detecting biomolecules with high sensitivity. This study utilizes SERS to analyze blood plasma for detecting both CRC and adenomatous polyps for the first time. Blood plasma samples are collected from healthy control subjects and patients diagnosed with adenomas and CRC. Using a real-time Raman system, SERS spectra for blood plasma samples are measured in 1 s. The collected SERS spectra are analyzed with partial least squares-discriminant analysis. Classification of normal versus CRC plus adenomatous polyps achieved diagnostic sensitivity of 86.4% and specificity of 80%. The results suggest that blood plasma SERS analysis could be a potential screening test to detect both CRC and adenomas.OCIS codes: (240.6695) Surface-enhanced Raman scattering, (170.1470) Blood or tissue constituent monitoring, (170.5660) Raman spectroscopy, (170.4580) Optical diagnostics for medicine