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Abstract: Foot care prevention programs can reduce the occurrence of foot ulcerations and amputations. The most important factor related to the development of foot ulcer is peripheral neuropathy, associated with loss of pain. Neuropathy can be associated with peripheral vascular disease and foot deformities. Five cornerstones for prevention should be respected, including regular examination of the feet and footwear, identification of high-risk patients, education of the patient and family, appropriate footwear, and treatment of nonulcerative pathology. After examination of the foot using the Semmes-Weinstein monofilament test, each patient can be assigned to one of the four risk categories to guide management. Foot care programs should be provided to high-risk categories of patients. Education plays an important role in prevention. The aim is to increase motivation and skills and enhance compliance with footwear advice. Items may include daily feet inspection and regular washing. Appropriate foot wear should protect against trauma. High-risk patients should participate in a foot care program set up by a multidisciplinary foot care team. [Copyright &y& Elsevier]

Cheese yield mainly depends on the amount and proportion of milk constituents; however, genetic variants of the proteins present in milk may also have an important effect. The objective of this research was to study the effect of the variants A and B of β-lactoglobulin (LG) on cheese yield using a model system consisting of skim milk powder fortified with different levels of a mixture containing α-lactalbumin and β-LG genetic variants (A, B, or A-B) in a 1:2 ratio. Fortified milk samples were subjected to pasteurization at 65°C for 30 min. Miniature cheeses were made by acidifying (pH = 5.9) fortified milk and incubating with rennet for 1 h at 32°C. The clot formed was cut, centrifuged at 2,600 x g for 30 min at 20°C and drained for determining cheese yield. Cheese-yielding capacity was expressed as actual yield (grams of cheese curd per 100 g of milk) and dry weight yield (grams of dried cheese curd per 100 g of milk). Free-zone capillary electrophoresis was used for determining β-LG A or B recovery in the curd during rennet-induced coagulation. The presence of β-LG variant B resulted in a significantly higher actual and dried weight cheese yield than when A or A-B were present at levels ≤0.675% of whey protein (WP) addition. Results of free-zone capillary electrophoresis allowed us to infer that β-LG B associates with the casein micelles during renneting, as shown by an increase in the recovery of this variant in the curd when β-LG B was added up to a maximum at 0.45% (equivalent to 0.675% WP). In general, actual or dried weight cheese yield increased as WP addition was increased from 0.225 to 0.675%. However, when WP addition ranged from 0.675 to 0.90%, a drastic drop in cheese yield was observed. This behavior may be because an increase in the aggregation of casein micelles with a concomitant inclusion of whey protein in the gel occurs at low levels of WP addition, whereas once the association of WP with the casein micelles reach a saturation point at addition levels higher than 0.675%, rearrangements of the gel network result in larger whey expulsion and syneresis. This knowledge is expected to be useful to maximize cheese yield and optimize processing conditions during cheese and cheese analogs manufacturing. [ABSTRACT FROM AUTHOR]

Abstract: With the main objective of test an inoculum of chitin-degrading rumen bacteria, 15 lambs with an average BW of 22.8kg were allotted at random (5 per treatment) to diets containing: T1=soybean meal, corn meal and corn stover (control treatment), T2=inclusion on the diet of 250g of shrimp shell waste (SSW) per 1000g (DM bases), in replacement of ingredients contained in T1, and T3=T2+inoculum made of Streptococcus milleri (chitin-degrading bacterium; 0.12ganimal−1 d−1). In general, the feed intake, weight gain and feed conversion were similar (P<0.05) between T1 and T3, but the lambs feed SSW without inoculum (T2) presented the lowest values. Concentration of total and cellulolytic bacteria was similar among treatments after 30d, but decreased in T2 and T3 after 60d. The population of chitinolytic bacteria increased (P<0.05) in the rumen of lambs fed 25% SSW. This increment was observed in lambs feed with or without inoculum. It is concluded that SSW can be efficiently used as a feedstuff for ruminants without any requirement of an adaptation period to the diet and decreasing the diet cost, if an inoculum of chitinolytic bacteria is added. [Copyright &y& Elsevier]

Due to its high prevalence and cost of care, estimated at 19 billion euros in France in 2018, diabetes is a major public health issue. Once adjusted, and according to the confidence ellipse, the remote monitoring procedure was estimated to be "cost saving". Conclusions The EDUC@DOM telemonitoring and tele-education program is cost-saving and allow the optimization of type 2 diabetic patient's care and in particular their glycemic balance. [Extracted from the article]

Due to the high ATP demand of myocardium, cardiac function is highly dependent on an efficient mitochondrial respiration. Ischemia and reperfusion injury (I/R) has severe impact on the function of the mitochondrial respiratory system. In donation after circulatory death (DCD), extent of I/R damage is decisive for posttransplant graft function. We aimed to investigate the mitochondrial respiration using high-resolution respirometry (HRR) in a porcine ex-situ heart perfusion (ESHP) model. 12 German domestic pigs (65-75kg) were used to simulate two different organ donation protocols: "donation after brain death" (DBD) (n=6) and DCD (n=6). ESHP was performed for 6 hours. Mitochondrial function in tissue homogenates of porcine myocardium was assessed by HRR. Samples were obtained at baseline (b), and after 1, 3, and 6 hours of ESHP. Comparison of repeated measurements were performed with two-way ANOVA followed by Sidak's post hoc test. The oxidative phosphorylation capacity after addition of NADH-generating substrates, fatty acids and succinate decreased slightly in the DCD group. A significant difference after 6 hours of perfusion was found (DBD 200.5±27.9 vs DCD 143.4±22.7 pmol−1·s−1·mL−1, p=0.038). The flux control ratio of the NADH-linked (Complex I) respiration declined in the DCD group (6h: DBD 0.16 vs DCD 0.05, p=0.007) (Figure 1). The mitochondrial outer membrane damage, assessed by cytochrome c addition was significantly lower after 6 hours of ESHP (p<0.001) without a difference between the groups. We performed the first in-depth analysis of mitochondrial respiratory function during ESHP in a DCD model. Interestingly, mitochondrial respiration is preserved over 3 hours in DCD hearts with a decline in function after 6 hours. Importantly, the initial mitochondrial outer membrane damage recovered over time in both groups. Next, the predictive value of HRR might be evaluated in clinical practice to promote organ acceptance in the future. [ABSTRACT FROM AUTHOR]

Background Treatment with direct-acting antiviral drugs in interferon-free regimens is currently recommended for viral hepatitis C recurrence after liver transplantation. There are limited data regarding its results in this population, and no optimal treatment scheme has yet been singled out. Methods We report our real-world results in liver transplant (LT) recipients. All patients were hepatitis C virus (HCV) monoinfected and completed a 12-week treatment course, followed 12 weeks later by HCV polymerase chain reaction testing with 12 IU/mL sensibility. Liver fibrosis was graded with the use of biopsies taken <12 months before treatment and stratified as early (0–1) or moderate to advanced (2–4) according to the Metavir score. Results Median postoperative time was 5.2 years. Genotype 3 was found in 66.7% of the sample. The following regimens were prescribed: daclatasvir-sofosbuvir with ( n = 11) or without ( n = 28) ribavirin. Genotypes 1 and 3 were evenly distributed between the regimens. Sustained virologic response (SVR) was obtained in 24 out of 28 patients (85.7%) who received daclatasvir-sofosbuvir and in all patients (100%) who received daclatasvir-sofosbuvir-ribavirin (global SVR 89.7%). All patients that failed treatment had genotype 3 HCV. Fibrosis was evaluated in 79.5% of the sample: 48.4% had early and 51.6% had moderate to advanced fibrosis, for which ribavirin was more commonly prescribed ( P = .001). Conclusions The SVR rate in our LT recipients was similar to that previously reported in the literature. The addition of ribavirin to DAA treatment appears to be justified in this population. [ABSTRACT FROM AUTHOR]

The effectiveness of liver preservation solutions remains in evidence. Cold ischemia time, steatosis, expanded criterion donors, operational cost, and survival represent important roles in its success. In a prospective cohort study between August 2009 and April 2014, 178 patients were allocated into an Institut Georges Lopez – 1 (IGL-1) solution group (63.5%) or histidine-tryptophan-ketoglutarate (HTK) group (36.5%). There were no differences among recipient’s characteristics including age, skin color, gender, Model for End-stage Liver Disease score, acute rejection, cholestasis, and reperfusion syndrome incidences. Also, donors, age average, skin color, donor risk index, time in intensive care unit, hemodynamic variables, infections, and steatosis incidences were similar. The average cold ischemia time was 494 minutes in the IGL-1 group and 489 minutes in the HTK group ( P = .77). Alanine aminotransferase and aspartate aminotransferase serum levels on the first postoperative day were 707 and 1185 mg/dL, respectively, with IGL-1 and 1298 and 2291 mg/dL, respectively, with HTK ( P = .016) and similar at day 15 ( P > .88). The incidence of delayed graft function was 4.5% with IGL-1 and 4.6% with HTK ( P = .90). The incidence primary nonfunction was 2.7% with IGL-1 and 3.1% with HTK ( P = .71). The incidence of perioperative death was 11.5% with IGL-1 and 13.8% with HTK ( P = .94). The survival in 30 months was 86% in IGL-1 group and 82% in HTK group ( P = .66). Both preservation solutions are efficient to liver transplantations with deceased donors. Major prospective trials are necessary to evaluate each preservation solution’s particularities. The preservation solution availability in each transplantation center must guide its use at the present moment. [ABSTRACT FROM AUTHOR]

To characterize the mechanism by which heterotrimeric G-proteins interpret the signals coining from various neurotransmitters of diverse efficacies (agonists and partial agonists) acting on α2A-adrenergic receptors, we used a fluorescent resonance energy transfer-based approach to study the effects of these partial agonists on the activation process of both the α2A-adrenergic receptor and its cognate Gi-protein. We show that ligands of different efficacies switch the receptor into distinct conformational states, which in turn set the speed and extent of the Gi-protein signaling. Thus, in cells the efficacy by which a receptor responds to diverse ligands is caused by the ability of the G-protein to differentiate between distinct receptor conformations. The data provide a new key characteristic underlying the mechanism of partial agonism at G-protein-coupled receptors. [ABSTRACT FROM AUTHOR]

During porphyrin biosynthesis the oxygen-independent coproporphyrinogen III oxidase (HemN) catalyzes the oxidative decarboxylation of the propionate side chains of rings A and B of coproporphyrinogen III to form protoporphyrinogen IX. The enzyme utilizes a 5′-deoxyadenosyl radical to initiate the decarboxylation reaction, and it has been proposed that this occurs by stereo-specific abstraction of the pro-S-hydrogen atom at the β-position of the propionate side chains leading to a substrate radical. Here we provide EPR-spectroscopic evidence for intermediacy of the latter radical by observation of an organic radical EPR signal in reduced HemN upon addition of S-adenosyl-L-me- thionine and the substrate coproporphyrinogen III. This signal (gav = 2.0029) shows a complex pattern of well resolved hyperfine splittings from at least five different hydrogen atoms. The radical was characterized using regiospecifically labeled (deuterium or 15N) coproporphyrinogen III molecules. They had been generated from a multienzyme mixture and served as efficient substrates. Reaction of HemN with coproporphyrinogen III, perdeuterated except for the methyl groups, led to the complete loss of resolved proton hyperfine splittings. Substrates in which the hydrogens at both α- and β-positions, or only at the β-positions of the propionate side chains, or those of the methylene bridges, were deuterated showed that there is coupling with hydrogens at the α-, β-, and methylene bridge positions. Deuterium or 15N labeling of the pyrrole nitrogens without labeling the side chains only led to a slight sharpening of the radical signal. Together, these observations clearly identified the radical signal as substrate-derived and indicated that, upon abstraction of the pro-S-hydrogen atom at the β-position of the propionate side chain by the 5′-deoxyadenosyl radical, a comparatively stable delocalized substrate radical intermediate is formed in the absence of electron acceptors. The observed hyperfine constants and g values show that this coproporphyrinogenyl radical is allylic and encompasses carbon atoms 3′, 3, and 4. [ABSTRACT FROM AUTHOR]