A fibrinogen-based precision microporous scaffold for tissue engineering

Fibrin has been long used as an effective scaffolding material to grow a variety of cells and tissue constructs. It has been utilized mainly as a hydrogel in varying concentrations to provide an environment in which suspended cells work to rearrange the fibers and lay down their own extracellular matrix. For these fibrin hydrogels to be useful in many tissue-engineering applications, the gels must be cultured for long periods of time in order to increase their mechanical strength to the levels of native tissues. High concentrations of fibrinogen increase the mechanical strength of fibrin hydrogels, but at the same time reduce the ability of cells within the scaffold to spread and survive. We present a method to create a microporous, nanofibriliar fibrin scaffold that has controllable pore size, porosity, and microstructure for applications in tissue engineering. Fibrin has numerous advantages as a scaffolding material as it is normally used by the body as temporary scaffolding for tissue regeneration and healing, and can be autologously sourced. We present here a scaffolding process which enhances the mechanical properties of the fibrin hydrogel by forming it surrounding poly(methyl-methacrylate) beads, then removing the beads with acetone to form an interconnected microporous network. The acetone serves the dual purpose of precipitating and fixing the fibrinogen-based scaffolds as well as adding strength to the network during polymer bead removal. Effects of fibrinogen concentration and time in acetone were examined as well as polymerization with thrombin. A natural crosslinker, genipin, was also used to add strength to the scaffolds, producing a Young's modulus of up to 184+/-5 kPa after 36 h of reaction. Using these methods we were able to produce microporous fibrin scaffolds that support cell growth and have mechanical properties similar to many native tissues.     

Regulatory pathways in inflammation

Tuning is a key aspect of inflammatory reaction essential in homeostasis and pathology. An emerging mechanism for negative regulation of proinflammatory cytokines is based on non-signaling IL-1/TLR receptors and chemokine receptors competing with signaling receptors for ligand binding and sustaining ligand internalization and degradation. Biological activities of IL-1R/TLR receptors are under control of membrane-bound binding molecules lacking the signaling domain, soluble receptor antagonists, and intracellular signaling inhibitors. The chemokine system includes at least three 'silent' receptors with distinct specificity and tissue distribution. D6 is the best characterized representative member of this class of negative regulators, binds most inflammatory, but not homeostatic, CC chemokines and shuttles in a ligand-independent way from the plasma membrane to endocytic compartments where chemokines are targeted to degradation. In vitro and in vivo evidence, including results with gene targeted mice, is consistent with the view that these non-signaling receptors for proinflammatory cytokines possess unique functional and structural features which make them ideally adapted to act as a decoy and scavenger receptors, with a non redundant role in dampening tissue inflammation and tuning draining lymph nodes reactivity.     

Abnormal expressions of the subunits of the UDP-<Emphasis Type="Italic">N</Emphasis>-acetylglucosamine: lysosomal enzyme, <Emphasis Type="Italic">N</Emphasis>-acetylglucosamine-1-phosphotransferase,result in the formation of cytoplasmic vacuoles resembling those of the I-cells

Defects in the multimeric enzyme, UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GNPT), result in the diseases of mucolipidosis (ML). This enzyme generates the mannose 6-phosphate residues on newly synthesized lysosomal enzymes for the efficient receptor-mediated transport to lysosomes. The enzyme contains alpha/beta and gamma subunits. Mutations in the alpha/beta subunit result in the classical ML II and IIIA, while defects in the gamma subunit results in the clinically milder ML IIIC. I-cells, a distinct histological feature characterized by the presence of abnormal cytoplasmic vacuoles, are detected in many cell types, most noticeably, in ML II patients. In this study, we investigated the interactions of the alpha/beta and gamma subunits in the pathogenesis of I-cells. We noted low and deranged alpha/beta subunit expressions in human mucolipidosis cell lines. Unexpectedly, high gamma subunit expressions were also observed. In normal mouse fibroblasts, when alpha/beta subunit was suppressed, abnormal cytoplasmic vacuoles were induced, and up-regulation of the gamma subunit was also observed. On the other hand, suppressing the gamma subunit resulted in biphasic responses of the alpha/beta subunit, while abnormal cytoplasmic vacuoles were not formed, regardless of the expression levels of the alpha/beta subunit. Our data suggest reciprocal feedback mechanisms between alpha/beta and the gamma subunits. A fine balance of the expressions of these subunits may play an important role in the formation of I-cells in this group of lysosomal storage disorders.     

Parental infertility and semen quality in male offspring: a follow-up study

Jensen et al. (Am J Epidemiol 2007;165:583-90) reported for the first time that men whose mothers had received fertility treatment had poor semen quality. This result could be confounded by the mothers' body mass index. Obesity is a strong predictor of fecundity and could have a programming effect on semen quality through hormonal factors or links to fetal growth. The authors of the current study tried to replicate the finding of Jensen et al. after controlling for maternal body mass index and other covariates using data from a recently conducted, population-based, Danish follow-up study on the association between maternal smoking during pregnancy in 1984-1987 and sons' semen quality, in which the participants were sampled according to levels of maternal smoking during pregnancy. After adjustment, sons of mothers who reported that they had been examined or treated for childlessness (n = 30) had a lower sperm concentration and total sperm count and fewer motile and morphologically normal spermatozoa in comparison with sons of mothers who had not been examined or treated for childlessness (n = 295). None of the differences (except for semen concentration) between the groups reached statistical significance, but the study has limited power. The findings were in the same direction as those reported by Jensen et al. and do not indicate that their results are confounded by maternal body mass index.     

Comparison of Susceptibilities of Anaerobic Bacteria to Cefmenoxime, Ceftriaxone, and Other Antimicrobial Compounds

The minimal inhibitory concentrations of cefmenoxime, cefotaxime, cefoxitin, ceftriaxone, chloramphenicol, clindamycin, and moxalactam were determined by agar dilution for 202 clinical isolates of anaerobic bacteria. Cefoxitin and moxalactam were the most active among the cephalosporin-like compounds.     

Factors contributing to hospital readmission in a Hong Kong regional hospital: a case-controlled study

BACKGROUND: As many as 50% of total hospital admissions are readmissions. Because the factors contributing to hospital readmission are multiple, and research findings are not conclusive, it is important for clinicians to gain an understanding of the key factors that contribute to readmission. OBJECTIVES:This study explores the factors contributing to hospital readmission and derives an explanatory model that can best identify characteristics of patients at high risk for hospital readmission. METHODS: This research was a case-controlled study with readmitted patients (n = 168) as the readmitted group and non-readmitted patients (n = 98) as the control group. The variables included demographic data, health assessment data, medical diagnosis, frequency of admissions, severity of illness, intensity of service and improvement of condition. The study sample was also interviewed to explore the patients' views on their repeated hospitalization. RESULTS: In the bivariate analysis significant differences between the study and control groups were multiple and generally consistent with findings in other studies. Using multiple logistic regression, however, the final model shows that only three factors best predict readmissions: frequency (3-4 times) of readmissions (OR = 9.96, p < .0001) and frequency (more than 5 times) of readmissions (OR = 15.73, p < .0001), financial assistance (OR = 5.03, p < .001), and severity of illness (OR = 3.12, p < .01). Our interview data suggest that the readmitted patients required assistance to accomplish daily living activities upon discharge and often returned to the hospital for the same health reason. CONCLUSION: The study findings suggest that patients who are frequently readmitted to the hospital are severely ill; are on public assistance; and may need special attention when discharged in order to attenuate repeated hospital readmission.