Unraveling molecular mechanisms involved in the development of leptin resistance using the pig as a model.

The increase in obesity worldwide underlines the need for research concerning its metabolic and genetic determinants. One of the most intriguing mechanisms regarding obesity involves leptin and its signaling cascade. Leptin is a key regulator contributing to the fine-tuned crosstalk between nutrient availability and appetite signaling in the central nervous system. Owing to ethical concerns, many human tissues are not readily available and pigs can serve as a good animal model owing to their comparable anatomy, metabolism and genetics. In the present study, we utilized the pig to investigate the possible impact of increased adiposity on the development of alterations within the leptin signaling pathway. Two divergent groups of pigs (High and Low) were defined based on a high and low amount of mesenteric fat. Cortex, cerebellum, hypothalamus, mesenteric, subcutaneous and retroperitoneal fat tissues were used to study changes in expression levels of 94 mRNA transcripts related to the leptin signaling pathway using the qPCR approach. No significant differences were found at the central nervous system, whereas the expression level of STAT1 was reduced in mesenteric fat and leptin (LEP) and interleukin 6 (IL6) were shown to be consistently increased in all analyzed fat compartments from pigs with a high amount of mesenteric fat. These results could imply the onset of leptin and pro-inflammatory cytokine overexpression at early stages of obesity in the analyzed pigs without affecting any key components in the central nervous system. Thus, these pigs showing a unique leptin deregulation in adipose tissues could be a useful translational resource for studies of obesity and leptin resistance phenotypes.

Short-term safety and effectiveness of sugammadex for surgical patients with end-stage renal disease: a two-centre retrospective study.

Sugammadex is a novel reversal agent for aminosteroid neuromuscular blocking drugs, especially rocuronium. Given its renal excretion, sugammadex is not recommended for patients with end-stage renal disease; however, reports exist of its use in this group of patients. This two-institutional retrospective observational study aimed to review the safety profile and effectiveness of sugammadex in surgical patients with end-stage renal disease who required pre-operative renal replacement therapy. Adult surgical patients with end-stage renal disease requiring pre-operative renal replacement therapy, who received sugammadex between April 2016 and January 2019, were studied. The primary outcome was the incidence of postoperative tracheal re-intubation within 48 h. The secondary outcome was the incidence of deferred tracheal extubation in the operating theatre. One hundred and fifty-eight patients were identified from 125,653 surgical patients: 48 patients (30%) underwent renal transplantation and 110 (70%) underwent non-renal transplantation procedures. There were 22 instances (14%) of deferred tracheal extubation due to surgical and/or pre-existing medical conditions. Out of the 136 patients who had the tracheal tube removed at the end of the procedure, three patients had their trachea re-intubated within 48 h: two patients developed pulmonary oedema resulting from volume overload; and one patient had worsening sepsis. No incidence of recurrence of neuromuscular blockade was observed. Of note, 24 (18%) patients were found to have incomplete neuromuscular blockade reversal with neostigmine but administration of sugammadex led to successful tracheal extubation. In conclusion, sugammadex appears to be safe and effective in adult patients with end-stage renal disease receiving pre-operative renal replacement therapy.

Shear stress increases hydraulic conductivity of cultured endothelial monolayers.

To examine the effect of shear stress on hydraulic conductivity (Lp) of bovine aortic endothelial cell monolayers grown on polycarbonate filters, we developed a rotating disk system, which imposed a defined shear stress while Lp was measured. A 10-cmH2O pressure differential was applied to monolayers, and baseline Lp was established between 1.65 +/- 0.85 and 4.94 +/- 1.05 x 10(-7) cm.s-1.cmH2O-1. One-hour exposure to 10 dyn/cm2 shear stress caused a significant (P < 0.05) increase in Lp by 2.16-fold (+/- 0.42), and Lp remained elevated when shear stress was removed. Three-hour exposure to shear stresses between 0.1 and 20.0 dyn/cm2 revealed a threshold for shear-induced increase in Lp of 0.5 dyn/cm2. At 20 dyn/cm2, Lp initially decreased by 30% (+/- 13.4%, P < 0.05) and then increased to a level 3.76-fold (+/- 0.83, P < 0.05) greater than baseline Lp at 3 h. The shear-induced increase in Lp was reversed with dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP, 1 mM) and could be significantly (P < 0.05) inhibited when monolayers were preincubated with 0.3 mM DBcAMP, a concentration that did not significantly affect baseline Lp. Furthermore, preincubation with a general phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (1 mM), completely blocked the shear-induced increase in Lp. On the basis of these results, we conclude that shear stress alters endothelial Lp through a cellular mechanism involving signal transduction, not by a purely physical mechanism.

Matrix multiplication by optical methods: experimental verification.

Matrix multiplication has been performed by optical analog methods using the scheme of Heinz et al. The most critical element was F(a), the spatial filter corresponding to the two-dimensional Fourier transform of a. In the operation c = b x a, errors in the c elements were 1-2% when the a elements were all approximately the same. Very large errors occurred when the a elements differed significantly, and these were used directly [instead of the F(a) derived values] in the numerical comparisons. These errors were attributed to the limited linear range of the amplitude transmittance characteristic of the film used. Suggestions for future work are made.

Matrix multiplication by optical methods.

The utilization of coherent optical correlation techniques in the performance of matrix multiplication by-optical analog methods has been investigated mathematically. Although the basic concepts have been known for some time, we have not been able to find explicit analyses in the existing literature. Since many correlations other than those corresponding to the desired matrix multiplication terms exist, methods of isolating the desired from the undesired terms are presented. Various spatial configurations for both the input and output arrays are discussed. For the special cases of 2 x 2 matrices the analyses are presented in greater detail. Using simple circ function distributions, the effects of finite-sized array elements and detector apertures are investigated.