The role of Serratia marcescens porins in antibiotic resistance

The outer membrane permeability of Serratia marcescens was studied by comparing porin-deficient mutants with their parental strains. Omp1-deficient strains were selected by moxalactam resistance, whereas mutants lacking the Omp2 porin were obtained by experimental infection with the SMP2 phage, whose primary receptor is the Omp2 porin. The role of porins was demonstrated in quinolone accumulation assays, where semiquantitative differences in accumulation were observed. Permeability coefficients to cephaloridine of Omp1 mutants were determined and compared with those of the parental strain. The clinical isolates S. marcescens HCPR1 and 866 showed 30- to 200-fold reduced permeability coefficients when Omp1 porin was absent.     

Ischemic preconditioning increases the tolerance of Fatty liver to hepatic ischemia-reperfusion injury in the rat

Hepatic steatosis is a major risk factor in ischemia-reperfusion. The present study evaluates whether preconditioning, demonstrated to be effective in normal livers, could also confer protection in the presence of steatosis and investigates the potential underlying protective mechanisms. Fatty rats had increased hepatic injury and decreased survival after 60 minutes of ischemia compared with lean rats. Fatty livers showed a degree of neutrophil accumulation and microcirculatory alterations similar to that of normal livers. However, in presence of steatosis, an increased lipid peroxidation that could be reduced with glutathione-ester pretreatment was observed after hepatic reperfusion. Ischemic preconditioning reduced hepatic injury and increased animal survival. Both in normal and fatty livers, this endogenous protective mechanism was found to control lipid peroxidation, hepatic microcirculation failure, and neutrophil accumulation, reducing the subsequent hepatic injury. These beneficial effects could be mediated by nitric oxide, because the inhibition of nitric oxide synthesis and nitric oxide donor pretreatment abolished and simulated, respectively, the benefits of preconditioning. Thus, ischemic preconditioning could be an effective surgical strategy to reduce the hepatic ischemia-reperfusion injury in normal and fatty livers under normothermic conditions, including hepatic resections, and liver transplantation.     

Hypergonadotrophinaemia with reduced uterine and ovarian size in women born small-for-gestational-age

BACKGROUND: Fetal growth restraint has been associated with FSH hypersecretion in early infancy and in early post-menarche, and with reduced uterine and ovarian size in adolescence. It is unknown whether these reproductive anomalies persist, respectively, into late infancy and into the reproductive age range. METHODS: We report follow-up findings in two age groups of girls. A cohort of infants [n=26; n=10 born appropriate-for-gestational-age (AGA) and n=16 born small-for-gestational-age (SGA)], who had been studied at the age of approximately 4 months, was assessed again at the age of 12 months. A cohort of teenagers (n=28), who had been studied at the age of approximately 14 years, was assessed again at the age of approximately 18 years; this group was complemented by a transversal cohort of similar age (n=19) for a total of 47 young women (n=27 AGA; n=20 SGA). In infants, only serum FSH was measured; adolescents underwent endocrine-metabolic screening, ultrasound assessment of uterine-ovarian size, and evaluation of body composition by dual X-ray absorptiometry. RESULTS: Serum FSH levels were higher in SGA than AGA infant girls at 4 and 12 months, and higher in SGA than AGA adolescents at 14 and 18 years (all P<0.01). Longitudinal ultrasound assessments disclosed a late-adolescent increment of uterine size that was less obvious in SGA than AGA girls. In contrast, ovarian volume remained stable in both subgroups. Compilation of longitudinal and transversal results at 18 years of age corroborated the persistent reduction in the uterine size of SGA girls (by approximately 20%; P<0.005) and in their ovarian volume (by approximately 40%; P<0.0001); moreover, SGA girls displayed not only a persistent elevation of FSH (by approximately 50%; P<0.001), but also a rise of LH and fasting insulin, as well as an excess of abdominal fat (all P<0.01). CONCLUSIONS: The gynaecology of young women born SGA was found to be characterized by hypergonadotrophinaemia and by a reduced uterine and ovarian size.     

Visual and Hearing Impairment Are Associated With Delirium in Hospitalized Patients: Results of a Multisite Prevalence Study

ObjectiveSensory deficits are important risk factors for delirium but have been investigated in single-center studies and single clinical settings. This multicenter study aims to evaluate the association between hearing and visual impairment or bi-sensory impairment (visual and hearing impairment) and delirium.DesignCross-sectional study nested in the 2017 “Delirium Day” project.Setting and ParticipantsPatients 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes, and hospices in Italy.MethodsDelirium was assessed with the 4AT (a short tool for delirium assessment) and sensory deficits with a clinical evaluation. We assessed the association between delirium, hearing and visual impairment in multivariable logistic regression models, adjusting for: Model 1, we included predisposing factors for delirium (ie, dementia, weight loss and autonomy in the activities of daily living); Model 2, we added to Model 1 variables, which could be considered precipitating factors for delirium (ie, psychoactive drugs and urinary catheters).ResultsA total of 3038 patients were included; delirium prevalence was 25%. Patients with delirium had a higher prevalence of hearing impairment (30.5% vs 18%; P < .001), visual impairment (24.2% vs 15.7%; P < .01) and bi-sensory impairment (16.2% vs 7.5%) compared with those without delirium. In the multivariable logistic regression analysis, the presence of bi-sensory impairment was associated with delirium in Model 1 [odds ratio (OR) 1.5, confidence interval (CI) 1.2–2.1; P = .00] and in Model 2 (OR 1.4; CI 1.1–1.9; P = .02), whereas the presence of visual and hearing impairment alone was not associated with delirium either in Model 1 (OR 0.8; CI 0.6–1.2, P = .36; OR 1.1; CI 0.8–1.4; P = .42) or in Model 2 (OR 0.8, CI 0.6–1.2, P = .27; OR 1.1, CI 0.8–1.4, P = .63).Conclusions and implicationsOur findings support the importance of routine screening and specific interventions by a multidisciplinary team to implement optimal management of sensory impairments and hence prevention and the management of the patients with delirium.     

Allogeneic stem-cell transplantation may overcome the adverse prognosis of unmutated VH gene in patients with chronic lymphocytic leukemia.

PURPOSE: To investigate whether allogeneic stem-cell transplantation (allo-SCT) may overcome the negative impact of unmutated VH genes in the outcome of patients with chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: We analyzed the outcome of patients who underwent SCT according to their VH mutational status. RESULTS: Thirty-four patients (14 allo-SCT and 20 autologous SCT [auto-SCT]) presented unmutated VH genes and 16 patients presented mutated VH genes (nine allo-SCT and seven auto-SCT). Tumoral burden pre-SCT was significantly higher in the allo-SCT patients independent of the VH mutational status. The risk of relapse was significantly higher after auto-SCT (5-year risk, 61%; 95% CI, 44% to 84%) than after allo-SCT (5-year risk 12%, 95% CI, 3% to 44%; P < .05). In the unmutated group, 13 of 20 auto-SCT and two of 14 allo-SCT patients experienced disease progression, with a risk of relapse at 5 years of 66% (95% CI, 48% to 93%) v 17% (95% CI, 5% to 60%), respectively (P = .01). CONCLUSION: These results show that allo-SCT may overcome the unfavorable effect of unmutated VH genes in patients with CLL.     

Feeding Jejunostomy after esophagectomy cannot be routinely recommended. Analysis of nutritional benefits and catheter-related complications

Background

Patients undergoing esophagectomy for cancer usually deal with malnourishment which increases postoperative morbimortality. The objective of this paper is to analyze the nutritional benefits of feeding jejunostomy (FJ) for early postoperative enteral nutrition (EN) and directly-related complications.

Generation of a Novel In Vitro Model to Study Endothelial Dysfunction from Atherothrombotic Specimens

Cardiovascular Drugs and Therapy - Endothelial dysfunction is central to the pathogenesis of acute coronary syndrome. The study of diseased endothelium is very challenging due to inherent...