The "systolic volume balance" method for the noninvasive estimation of cardiac output based on pressure wave analysis

Cardiac output (CO) monitoring is essential for the optimal management of critically ill patients. Several mathematical methods have been proposed for CO estimation based on pressure waveform analysis. Most of them depend on invasive recording of blood pressure and require repeated calibrations, and they suffer from decreased accuracy under specific conditions. A new systolic volume balance (SVB) method, including a simpler empirical form (eSVB), was derived from basic physical principles that govern blood flow and, in particular, a volume balance approach for the conservation of mass ejected into and flowed out of the arterial system during systole. The formulas were validated by a one-dimensional model of the systemic arterial tree. Comparisons of CO estimates between the proposed and previous methods were performed in terms of agreement and accuracy using "real" CO values of the model as a reference. Five hundred and seven different hemodynamic cases were simulated by altering cardiac period, arterial compliance, and resistance. CO could be accurately estimated by the SVB method as follows: CO = C × PP(ao)/(T - P(sm) × T(s)/P(m)) and by the eSVB method as follows: CO = k × C × PP(ao)/T, where C is arterial compliance, PP(ao) is aortic pulse pressure, T is cardiac period, P(sm) is mean systolic pressure, T(s) is systolic duration, P(m) is mean pressure, and k is an empirical coefficient. SVB applied on aortic pressure waves did not require calibration or empirical correction for CO estimation. An empirical coefficient was necessary for brachial pressure wave analysis. The difference of SVB-derived CO from model CO (for brachial waves) was 0.042 ± 0.341 l/min, and the limits of agreement were -0.7 to 0.6 l/min, indicating high accuracy. The intraclass correlation coefficient and root mean square error between estimated and "real" CO were 0.861 and 0.041 l/min, respectively, indicating very good accuracy. eSVB also provided accurate estimation of CO. An in vivo validation study of the proposed methods remains to be conducted.     

Idiopathic carpal tunnel syndrome caused by carpal stenosis.

Computed tomography was used to measure the cross-sectional area of the carpal canals in normal controls of both sexes and in women with idiopathic carpal tunnel syndrome. The women controls had significantly smaller carpal canals than the men controls both proximally and distally. In the patients both the proximal and distal cross-sectional areas were significantly reduced compared with the women controls. The measurements showed that carpal canal stenosis is associated with idiopathic carpal tunnel syndrome, narrowing of the canal is bilateral in patients who have unilateral symptoms, and narrowing is greater in the proximal carpal canal. There was no correlation between age and the size of the canal. The difference in the size of the carpal canal between normal men and women might explain the tendency of women to develop carpal tunnel syndrome. The lack of correlation between age and the size of the canal suggests that stenosis of the carpal canal is inherited rather than acquired. Symptoms arise only later in life, when degenerated changes in the content or the walls of the carpal canal compete with the median nerve for space and its function becomes impaired by compression.     

Synthesis and Evaluation of Chloramphenicol Homodimers: Molecular Target,Antimicrobial Activity,and Toxicity against Human Cells

As fight against antibiotic resistance must be strengthened, improving old drugs that have fallen in reduced clinical use because of toxic side effects and/or frequently reported resistance, like chloramphenicol (CAM), is of special interest. Chloramphenicol (CAM), a prototypical wide-spectrum antibiotic has been shown to obstruct protein synthesis via binding to the bacterial ribosome. In this study we sought to identify features intensifying the bacteriostatic action of CAM. Accordingly, we synthesized a series of CAM-dimers with various linker lengths and functionalities and compared their efficiency in inhibiting peptide-bond formation in an Escherichia coli cell-free system. Several CAM-dimers exhibited higher activity, when compared to CAM. The most potent of them, compound 5, containing two CAM bases conjugated via a dicarboxyl aromatic linker of six successive carbon-bonds, was found to simultaneously bind both the ribosomal catalytic center and the exit-tunnel, thus revealing a second, kinetically cryptic binding site for CAM. Compared to CAM, compound 5 exhibited comparable antibacterial activity against MRSA or wild-type strains of Staphylococcus aureus, Enterococcus faecium and E. coli, but intriguingly superior activity against some CAM-resistant E. coli and Pseudomonas aeruginosa strains. Furthermore, it was almost twice as active in inhibiting the growth of T-leukemic cells, without affecting the viability of normal human lymphocytes. The observed effects were rationalized by footprinting tests, crosslinking analysis, and MD-simulations.     

One-stage full-mouth disinfection to overcome intra-oral transmission of periodontopathogens

The oral cavity offers a range of different niches where periodontopathogens can adhere and survive (e.g. the mucosa, the tongue, the tonsils, the saliva and all intra-oral hard surfaces such as teeth, dentures, oral implants). Transmission of bacteria from one niche to another is likely to occur. Recent studies, for example, illustrated that initially sterile abutments of oral implants were rapidly colonized by bacteria from the subgingival environment around teeth. This transmission of bacteria can occur spontaneously via the saliva, or by means of oral hygiene aids and/or dental instruments. Such an intra-oral transmission, if it occurs at a high speed, could jeopardize the outcome of periodontal therapy. To overcome a bacterial transmission, a 'one-stage full-mouth disinfection' was recently introduced for the treatment of periodontal infections. This new treatment strategy resulted in significant clinical and microbiological improvements when compared with the standard sequential treatment.     

Multiple roles and interactions of tbx4 and tbx5 in development of the respiratory system

Normal development of the respiratory system is essential for survival and is regulated by multiple genes and signaling pathways. Both Tbx4 and Tbx5 are expressed throughout the mesenchyme of the developing lung and trachea; and, although multiple genes are known to be required in the epithelium, only Fgfs have been well studied in the mesenchyme. In this study, we investigated the roles of Tbx4 and Tbx5 in lung and trachea development using conditional mutant alleles and two different Cre recombinase transgenic lines. Loss of Tbx5 leads to a unilateral loss of lung bud specification and absence of tracheal specification in organ culture. Mutants deficient in Tbx4 and Tbx5 show severely reduced lung branching at mid-gestation. Concordant with this defect, the expression of mesenchymal markers Wnt2 and Fgf10, as well as Fgf10 target genes Bmp4 and Spry2, in the epithelium is downregulated. Lung branching undergoes arrest ex vivo when Tbx4 and Tbx5 are both completely lacking. Lung-specific Tbx4 heterozygous;Tbx5 conditional null mice die soon after birth due to respiratory distress. These pups have small lungs and show severe disruptions in tracheal/bronchial cartilage rings. Sox9, a master regulator of cartilage formation, is expressed in the trachea; but mesenchymal cells fail to condense and consequently do not develop cartilage normally at birth. Tbx4;Tbx5 double heterozygous mutants show decreased lung branching and fewer tracheal cartilage rings, suggesting a genetic interaction. Finally, we show that Tbx4 and Tbx5 interact with Fgf10 during the process of lung growth and branching but not during tracheal/bronchial cartilage development.     

Approaching the serpentine factor at a local scale—a study in an ultramafic area in northern Greece

We explore factors responsible for vegetation differentiation in a small-scale serpentine area, and attempt to provide new insights in the complexity of the serpentine factor at community level. We sampled 49 quadrats. From each quadrat physical and chemical soil parameters were measured and species composition, altitude, inclination, aspect and coordinates were recorded. Quadrats were classified and ordination analyses were used to explore the environmental gradients and to estimate the explanatory power of the variables. Generalized linear models were used to investigate the response of species to environmental factors. Variance partitioning was applied to calculate the proportion of variance attributed to different groups of explanatory variables. The gradients revealed were related to soil texture, nutrient contents, calcium deficiency, chromium content, climatic parameters and grazing and disturbance intensity. Variance partitioning showed that the highest proportions of variance were attributed to the nutrients and physiographic (including soil texture) variables, while smaller but notable proportions of variance were attributed to geographical coordinates and to metal contents. Our study shows that vegetation differentiation at a local scale is determined by a complex factor of soil properties and climatic parameters, together with variation in disturbance and succession.