The metabolism of gluconate in Escherichia coli. The subsidiary system and the nature of the gntS gene

The transport and phosphorylation of gluconate in E. coli occurs through two systems (GntI and GntII) which duplicate activities. bioH-asddeletion mutants do not grow on media with gluconate as sole carbon source because they lack the GntI system and do not express GntII. Although E. coli C177 is a Δ(bioH-asd) mutant, it carries the pyrB linked mutation gnt177 that enables it to metabolize this substrate through inducible expression of the GntII system. Several gntS derivatives which are unable to grow on gluconate were isolated from E. coli C177 by spontaneous curing of the transposon Tn10 previously inserted at the gntS locus (zjf::Tn10, min 95.3). A representative gntS mutant, E. coli TI141A retained the ability to take up gluconate but had lost the thermosensitive gluconokinase activity (gene gntV, min 96.9). Furthermore, it could be demonstrated that gntV is repressed in E. coli TI141A. The results indicate that gntS might specify a trans-acting positive regulator involved in the control of at least the expression of the thermosensitive gluconokinase (GntII), instead of a gluconate uptake system as it was previously postulated. Likewise, these results can be used to reconsider whether the locus altered by the gnt177 lesion is allelic with that of the GntII permease instead of a regulator, as it was originally postulated.     

Prevalence and mortality of patients with palliative needs in an acute respiratory setting

IntroductionNECPAL is a tool for identification of patients with advanced chronic disease in need of palliative care. The main objective of the study is to know the prevalence of patients with palliative needs in an acute respiratory ward in a Spanish tertiary hospital using NECPAL. A second objective of the study is to know the annual mortality rate of these patients.Materials and methodsCross sectional study and prospective monitoring of a cohort identified as palliative patients with the NECPAL tool for 12 months. Patient identification was performed in patients admitted to the respiratory ward of our hospital for longer than 3 days. We have assessed the annual vital status (deceased or not deceased) of patients and have recorded demographics, clinical and functional data, as well as the use of healthcare resources.ResultsWe monitored a cohort of 363 patients. Of them, 87 patients (24.3%) (IC 95% 19–30) were identified as NECPAL positive. 60% of patients (n = 64) died within 12 months of their admission. There was no significant difference in the mortality ratio of oncologic versus non oncologic patients. In a multivariable analysis, mortality was associated with demand by patients or relatives for palliative care and with the presence of specific disease progression markers or indicators.Conclusionsprevalence of patients with palliative needs in acute respiratory wards is high (one out of four patients). 60% of the patients identified as NECPAL positive in our cohort died in the first 12 months. Training of healthcare professionals as well as availability of appropriate resources are indispensable factors to improve care of this population.     

Geographic variation of gallbladder cancer mortality and risk factors in Chile: a population-based ecologic study

Chile's gallbladder cancer rates are among the highest in the world, being the leading cause of cancer deaths among Chilean women. To provide insights into the etiology of gallbladder cancer, we conducted an ecologic study examining the geographical variation of gallbladder cancer and several putative risk factors. The relative risk of dying from gallbladder cancer between 1985 and 2003 was estimated for each of the 333 Chilean counties, using a hierarchical Poisson regression model, adjusting for age, sex and geographical location. The risk of gallbladder cancer mortality was analyzed in relation to region, poverty, Amerindian (Mapuche) population, typhoid fever and access to cholecystectomy, using logistic regression analysis. There were 27,183 gallbladder cancer deaths, with age and sex-adjusted county mortality rates ranging from 8.2 to 12.4 per 100,000 inhabitants. Rates were highest in inland and southern regions. Compared to the northern-coast, the northern-inland region had a 10-fold risk (95% of confidence interval (95% CI): 2.4-42.2) and the southern-inland region had a 26-fold risk (95% CI: 6.0-114.2). Independent of region, other risk factors for gallbladder cancer included a high Mapuche population (Odds ratio (OR):3.9, 95% CI 1.8-8.7), high typhoid fever incidence (OR:2.9, 95% CI 1.2-6.9), high poverty (OR:5.1, 95% CI 1.6-15.9), low access to cholecystectomy (OR:3.9, 95% CI 1.5-10.1), low access to hospital care (OR:14.2, 95% CI 4.2-48.7) and high urbanization (OR:8.0, 95% CI 3.4-18.7). Our results suggest that gallbladder cancer in Chile may be related to both genetic factors and poor living conditions. Future analytic studies are needed to further clarify the role of these factors in gallbladder cancer etiology.     

Impact of resveratrol on bone repair in rats exposed to cigarette smoke inhalation: histomorphometric and bone-related gene expression analysis

This study investigated the effect of resveratrol on bone healing and its influence on the gene expression of bone-related markers in rats exposed to cigarette smoke. Two calvarial defects were created in each of 60 rats, which were assigned equally (n = 20) to three groups: (1) resveratrol (10 mg/kg) + smoke exposure (SMK + RESV); (2) placebo + smoke exposure (SMK + PLA); or (3) placebo + no smoke exposure (NS + PLA). Substances were administered daily for 30 days following surgery. Smoke inhalation was started 7 days before surgery and continued for 30 days after surgery. One defect was processed for histomorphometric analysis and the other was used for mRNA quantification of bone-related gene expression by qPCR. The remaining defect was smaller in the SMK + RESV (2.27 ± 0.61 mm, P = 0.0003) and NS + PLA (2.17 ± 0.74 mm, P = 0.0005) groups than in the SMK + PLA group (3.12 ± 0.47 mm). Higher levels of Runx2 were observed in the NS + PLA group than in the smoke exposure groups (vs. SMK + PLA, P = 0002; vs. SMK + RESV, P = 0.052); levels of Lrp-5 were also higher in the no smoke exposure group (vs. SMK + RESV, P = 0.009; vs. SMK + PLA, P = 0.003). Resveratrol therapy decreased RANKL/OPG expression when compared to placebo (SMK + RESV vs. SMK + PLA, P = 0.017). Dkk1 levels were decreased in the SMK + RESV group when compared to the SMK + PLA (P = 0.006) and NS + PLA groups (P = 0.005). In conclusion, resveratrol optimizes the repair of critical-sized bone defects, up-regulating the gene expression of important bone remodelling markers in rats exposed to cigarette smoke inhalation.     

How far have biological therapies come in regenerative sports medicine?

Introduction: Regular engagement in sports produces many health benefits, but also exposes to increased injury risk. The quality of medical care available is crucial not only for sports trauma but also to avoid overuse syndromes and post-traumatic degenerative conditions.

Areas covered: We provide background information on some clinical needs in sport injuries and describe the main families of biological products used in clinical practice. We also discuss limitations of the current clinical experience.

Expert opinion: Sport and exercise impairment affects different segments of the population with different needs. The exceptional demands of elite athletes and subsequent media coverage have created hype around regenerative therapies. Statistical evidence, whether weak (cell products) or moderate (PRPs), is not enough to drive medical decisions because of the heterogeneity of the biological products available and their application procedures. Moreover, the specific needs of the different segments of the population along with the available clinical evidence for each musculoskeletal condition should be considered in the decision-making process. There is urgent need to develop regenerative protocols combined with post-intervention rehabilitation, and gather meaningful clinical data on the safety and efficacy of these interventions in the different populations segments.     

Obtaining reliable intraoral digital scans for an implant-supported complete-arch prosthesis: A dental technique

This article describes a technique for obtaining an accurate complete-arch digital scan for an edentulous patient. To achieve this, an auxiliary polymeric device that simulates a denture is designed, fabricated, and placed in the mouth. This device, having the geometry of a typical dental arch, facilitates the digitalization of the edentulous complete arch. This is because the change in radius of the curvature (change of geometry) enables the scanner to perform a more accurate alignment. Initially, the necessary location of the implants is acquired, and then the soft tissue is added. This technique can achieve accurate complete-arch digital scans. Distances between implants are closer to the gold standard when using this auxiliary geometry piece than those obtained without using it.     

Comparison of High Ribavirin Induction Versus Standard Ribavirin Dosing, Plus Peginterferon-α for the Treatment of Chronic Hepatitis C in HIV-Infected Patients: The PERICO Trial

Background.?Ribavirin (RBV) exposure seems to be critical to maximize treatment response in human immunodeficiency virus (HIV)-positive patients with chronic hepatitis C virus (HCV) infection. Methods.?HIV/HCV-coinfected individuals naive to interferon were prospectively randomized to receive peginterferon-α-2a (180?μg/d) plus either RBV standard dosing (1000 or 1200?mg/d if <75 or ≥75?kg, respectively) or RBV induction (2000?mg/d) along with subcutaneous erythropoietin β (450?IU/kg/wk), both during the first 4 weeks, followed by standard RBV dosing until completion of therapy. Early stopping rules at weeks 12 and 24 were applied in patients with suboptimal virological response. Results.?A total of 357 patients received ≥1 dose of the study medication. No differences in main baseline characteristics were found when comparing treatment arms. Sustained virological response (SVR) was attained by 160 (45%) patients, with no significant differences between RBV induction and standard treatment arms (SVR in 72 of 169 patients [43%] vs 88 of 188 [47%], respectively). At week 4, undetectable HCV RNA (29% vs 25%) and mean RBV trough concentration (2.48 vs 2.14?μg/mL) were comparable in both arms, whereas mean hemoglobin decay was less pronounced in the RBV induction plus erythropoietin arm than in the RBV standard dosing arm (-1.7 vs -2.3?mg/dL; P?相似文献   

Genetic analysis of the IL8 gene polymorphism (rs4073) in generalized aggressive periodontitis

ObjectivesInterleukin (IL)-8 is an important chemokine for regulation of the inflammatory response. A single nucleotide polymorphism (SNP) reference sequence (rs) 4073 in the IL8 gene has been shown to regulate IL-8 levels after stimulation with lipopolysaccharide. This study investigates the transmission pattern of the IL8 rs4073 risk allele A and its association with susceptibility to aggressive periodontitis (AgP) in families and in a case–control cohort of unrelated individuals from a Brazilian population.DesignGenotyping was performed by standard polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP) in 13 nuclear families and 184 unrelated subjects. Statistical analysis was performed using the transmission disequilibrium test (TDT) for the family dataset and Chi-square test and multivariate logistic regression modelling for the case–control dataset.ResultsTDT analyses did not detect evidence of over transmission of IL8 rs4073 alleles in affected and unaffected family members (allele T: 52%; allele A: 48%; p = 0.2252). How expected, analyses of cases and unrelated controls showed a significant and inverse association of age with AgP; however, a lack of association between genotypes, ethnic groups and generalized AgP was observed.ConclusionsThe SNP (rs4073) was not associated with AgP in unrelated individuals and there is no evidence of over transmission of the alleles in families with AgP, from Brazilian individuals.