Escherichia coli O115 has been isolated from healthy sheep and was shown to be associated with attaching–effacing (AE) lesions in the large intestine. Following previous observations of interactions ...between E. coli O157 and O26, the aim of the present study was to assess what influence an O115 AE E. coli (AEEC) would have on E. coli O157 colonisation in vitro and in vivo. We report that E. coli O115- and O157-associated AE lesions were observed on HEp-2 cells and on the mucosa of ligated ovine spiral colon. In single strain inoculum, E. coli O115 associated intimately with HEp-2 cells and the spiral colon in greater numbers than E. coli O157:H7. However, in mixed inoculum studies, the number of E. coli O115 AE lesions was significantly reduced suggesting negative interference by E. coli O157. Use of the ligated colon model in the present work has allowed in vitro observations to be extended and confirmed whilst using a minimum of experimental animals. The findings support a hypothesis that some AEEC can inhibit adhesion of other AEEC in vivo. The mechanisms involved may prove to be of utility in the control of AE pathovars.
Background Elective abdominal aortic aneurysm (AAA) surgery relies on balancing the risk of the intervention against the risk of the aneurysm causing death. Although much is known about intervention ...at 5.5 cm, little is known about the fate of the patient unfit for elective surgery at this threshold. Medical therapy and endovascular surgery have revolutionized management of aortic aneurysms in the last 20 years and are thought to have affected rupture rates. Methods MEDLINE via PubMed, EMBASE, and the Cochrane Library Database were searched for studies reporting follow-up of untreated large AAA approach from inception to January 2014. Data were pooled using random-effects analysis with standardized mean differences and 95% confidence intervals (CIs) reported. The primary end points were rupture rates and all-cause mortality per year by AAA size. Results The search strategy identified 1892 citations, of which 11 studies comprising 1514 patients experiencing 347 ruptured AAA were included. The overall incidence of ruptured AAA in patients with AAA >5.5 cm was 5.3% (95% CI, 3.1%-7.5%) per year. This represented cumulative yearly rupture rates of 3.5% (95% CI, −1.6% to 8.7%) in AAAs 5.5 to 6.0 cm, 4.1% (95% CI, −0.7% to 9.0%) in AAAs 6.1 to 7.0 cm, and 6.3% (95% CI, −1.8% to 14.3%) in AAAs >7.0 cm. There was no heterogeneity between studies ( I2 = 0%). Only 32% of these patients were offered repair on rupturing an AAA, with a perioperative mortality of 58% (95% CI, 32%-83%). The risk of death from causes other than AAA was higher than the risk of death from rupture. Conclusions Rupture rates of untreated AAA were lower than those currently quoted in the literature. Non-AAA-related mortality in this group of patients is high.
Prosthetic joint infection is a devastating complication of knee replacement. The risk of developing a prosthetic joint infection is affected by patient, surgical, and health-care system factors. ...Existing evidence is limited by heterogeneity in populations studied, short follow-up, inadequate power, and does not differentiate early prosthetic joint infection, most likely related to the intervention, from late infection, more likely to occur due to haematogenous bacterial spread. We aimed to assess the overall and time-specific associations of these factors with the risk of revision due to prosthetic joint infection following primary knee replacement.
In this cohort study, we analysed primary knee replacements done between 2003 and 2013 in England and Wales and the procedures subsequently revised for prosthetic joint infection between 2003 and 2014. Data were obtained from the National Joint Registry linked to the Hospital Episode Statistics data in England and the Patient Episode Database for Wales. Each primary replacement was followed for a minimum of 12 months until the end of the observation period (Dec 31, 2014) or until the date of revision for prosthetic joint infection, revision for another indication, or death (whichever occurred first). We analysed the data using Poisson and piecewise exponential multilevel models to assess the associations between patient, surgical, and health-care system factors and risk of revision for prosthetic joint infection.
Of 679 010 primary knee replacements done between 2003 and 2013 in England and Wales, 3659 were subsequently revised for an indication of prosthetic joint infection between 2003 and 2014, after a median follow-up of 4·6 years (IQR 2·6–6·9). Male sex (rate ratio RR for male vs female patients 1·8 95% CI 1·7–2·0), younger age (RR for age ≥80 years vs <60 years 0·5 0·4–0·6), higher American Society of Anaesthesiologists ASA grade (RR for ASA grade 3–5 vs 1, 1·8 1·6–2·1), elevated body-mass index (BMI; RR for BMI ≥30 kg/m2vs <25 kg/m2 1·5 1·3–1·6), chronic pulmonary disease (RR 1·2 1·1–1·3), diabetes (RR 1·4 1·2–1·5), liver disease (RR 2·2 1·6–2·9), connective tissue and rheumatic diseases (RR 1·5 1·3–1·7), peripheral vascular disease (RR 1·4 1·1–1·7), surgery for trauma (RR 1·9 1·4–2·6), previous septic arthritis (RR 4·9 2·7–7·6) or inflammatory arthropathy (RR 1·4 1·2–1·7), operation under general anaesthesia (RR 1·1 1·0–1·2), requirement for tibial bone graft (RR 2·0 1·3–2·7), use of posterior stabilised fixed bearing prostheses (RR for posterior stabilised fixed bearing prostheses vs unconstrained fixed bearing prostheses 1·4 1·3–1·5) or constrained condylar prostheses (3·5 2·5–4·7) were associated with a higher risk of revision for prosthetic joint infection. However, uncemented total, patellofemoral, or unicondylar knee replacement (RR for uncemented vs cemented total knee replacement 0·7 95% CI 0·6–0·8, RR for patellofemoral vs cemented total knee replacement 0·3 0·2–0·5, and RR for unicondylar vs cemented total knee replacement 0·5 0·5–0·6) were associated with lower risk of revision for prosthetic joint infection. Most of these factors had time-specific effects, depending on the time period post-surgery.
We have identified several risk factors for revision for prosthetic joint infection following knee replacement. Some of these factors are modifiable, and the use of targeted interventions or strategies could lead to a reduced risk of revision for prosthetic joint infection. Non-modifiable factors and the time-specific nature of the effects we have observed will allow clinicians to appropriately counsel patients preoperatively and tailor follow-up regimens.
National Institute for Health Research.
We compared the risks of re-revision and mortality between two-stage and single-stage revision surgeries among patients with infected primary hip arthroplasty. Patients with a periprosthetic joint ...infection (PJI) of their primary arthroplasty revised with single-stage or two-stage procedure in England and Wales between 2003 and 2014 were identified from the National Joint Registry. We used Poisson regression with restricted cubic splines to compute hazard ratios (HRs) at different postoperative periods. The total number of revisions and re-revisions undergone by patients was compared between the two strategies. In total, 535 primary hip arthroplasties were revised with single-stage procedure (1,525 person-years) and 1,605 with two-stage procedure (5,885 person-years). All-cause re-revision was higher following single-stage revision, especially in the first three months (HR at 3 months = 1.98 (95% confidence interval (CI) 1.14 to 3.43), p = 0.009). The risks were comparable thereafter. Re-revision for PJI was higher in the first three postoperative months for single-stage revision and waned with time (HR at 3 months = 1.81 (95% CI 1.22 to 2.68), p = 0.003; HR at 6 months = 1.25 (95% CI 0.71 to 2.21), p = 0.441; HR at 12 months = 0.94 (95% CI 0.54 to 1.63), p = 0.819). Patients initially managed with a single-stage revision received fewer revision operations (mean 1.3 (SD 0.7) vs 2.2 (SD 0.6), p < 0.001). Mortality rates were comparable between these two procedures (29/10,000 person-years vs 33/10,000). The risk of unplanned re-revision was lower following two-stage revision, but only in the early postoperative period. The lower overall number of revision procedures associated with a single-stage revision strategy and the equivalent mortality rates to two-stage revision are reassuring. With appropriate counselling, single-stage revision is a viable option for the treatment of hip PJI.
Grand and Semigrand Canonical Basin-Hopping Calvo, F; Schebarchov, D; Wales, D. J
Journal of chemical theory and computation,
02/2016, Letnik:
12, Številka:
2
Journal Article
Recenzirano
Odprti dostop
We introduce grand and semigrand canonical global optimization approaches using basin-hopping with an acceptance criterion based on the local contribution of each potential energy minimum to the ...(semi)grand potential. The method is tested using local harmonic vibrational densities of states for atomic clusters as a function of temperature and chemical potential. The predicted global minima switch from dissociated states to clusters for larger values of the chemical potential and lower temperatures, in agreement with the predictions of a model fitted to heat capacity data for selected clusters. Semigrand canonical optimization allows us to identify particularly stable compositions in multicomponent nanoalloys as a function of increasing temperature, whereas the grand canonical potential can produce a useful survey of favorable structures as a byproduct of the global optimization search.
Pertussis morbidity and mortality disproportionately affect infants younger than 1 year, who constitute 70% of deaths from pertussis. In 2017, 43% of infants younger than 6 months diagnosed with ...pertussis were hospitalized. In 2012, the Advisory Committee on Immunization Practices recommended that all pregnant women should receive Tdap (tetanus-diphtheria-acellular pertussis) vaccine between 27- and 36-weeks gestation in an effort to reduce infant pertussis morbidity and mortality. However, Tdap vaccination rates among pregnant women remain far from robust. The aim of this study was to assess factors associated with maternal Tdap uptake to help providers identify best practices that can improve Tdap receipt and identify women at risk for not receiving this important vaccine.
A retrospective cross-sectional study.
A review of prenatal and delivery records was performed on all maternal-infant dyads with infants older than 36 weeks gestation admitted to the term nursery at Albany Medical Center from January 1, 2016 to April 16, 2016. A chi-squared analysis using STATA®, version 14.1, was performed to determine if any variables were associated with Tdap uptake, with statistical significance defined as P < 0.05. Multivariate analysis was performed to identify the variables which had the greatest effect on Tdap receipt.
Tdap vaccine was received by 65.8% of pregnant women (n = 400) in the study; median gestational age of receipt was 30 weeks. Maternal influenza vaccine receipt, infant hepatitis B vaccine receipt, provider recommendation of Tdap vaccination, and on-site availability of Tdap vaccine were all positively associated with maternal Tdap receipt during pregnancy.
Receipt of Tdap by pregnant women was highest in those who had received a provider recommendation about its benefits and who also received influenza vaccine during pregnancy. Because women who received the influenza vaccine themselves and also consented to have their infants receive the hepatitis B vaccine had significantly higher uptake rates, encouraging vaccines usage and combating vaccine hesitancy in general can improve Tdap uptake rates. A small, but statistically significant association with receipt of assisted reproductive technologies was also seen, meriting future research.
•In this study, 65.8% of pregnant women received tetanus-diphtheria-acellular pertussis (Tdap) during their pregnancy.•Pregnant women were more likely to receive Tdap if their obstetric provider recommended the vaccine.•Women who received influenza vaccine were more likely to receive Tdap.•Women were more likely to receive Tdap if the vaccine was readily available at their obstetric provider's office.
The clinical translation of cationic α-helical antimicrobial peptides (AMPs) has been hindered by structural instability, proteolytic degradation and in vivo toxicity from nonspecific membrane lysis. ...Although analyses of hydrophobic content and charge distribution have informed the design of synthetic AMPs with increased potency and reduced in vitro hemolysis, nonspecific membrane toxicity in vivo continues to impede AMP drug development. Here, we analyzed a 58-member library of stapled AMPs (StAMPs) based on magainin II and applied the insights from structure-function-toxicity measurements to devise an algorithm for the design of stable, protease-resistant, potent and nontoxic StAMP prototypes. We show that a lead double-stapled StAMP named Mag(i+4)1,15(A9K,B21A,N22K,S23K) can kill multidrug-resistant Gram-negative pathogens, such as colistin-resistant Acinetobacter baumannii in a mouse peritonitis-sepsis model, without observed hemolysis or renal injury in murine toxicity studies. Inputting the amino acid sequences alone, we further generated membrane-selective StAMPs of pleurocidin, CAP18 and esculentin, highlighting the generalizability of our design platform.
Context:
GLIS3 (GLI-similar 3) is a member of the GLI-similar zinc finger protein family encoding for a nuclear protein with 5 C2H2-type zinc finger domains. The protein is expressed early in ...embryogenesis and plays a critical role as both a repressor and activator of transcription. Human GLIS3 mutations are extremely rare.
Objective:
The purpose of this article was determine the phenotypic presentation of 12 patients with a variety of GLIS3 mutations.
Methods:
GLIS3 gene mutations were sought by PCR amplification and sequence analysis of exons 1 to 11. Clinical information was provided by the referring clinicians and subsequently using a questionnaire circulated to gain further information.
Results:
We report the first case of a patient with a compound heterozygous mutation in GLIS3 who did not present with congenital hypothyroidism. All patients presented with neonatal diabetes with a range of insulin sensitivities. Thyroid disease varied among patients. Hepatic and renal disease was common with liver dysfunction ranging from hepatitis to cirrhosis; cystic dysplasia was the most common renal manifestation. We describe new presenting features in patients with GLIS3 mutations, including craniosynostosis, hiatus hernia, atrial septal defect, splenic cyst, and choanal atresia and confirm further cases with sensorineural deafness and exocrine pancreatic insufficiency.
Conclusion:
We report new findings within the GLIS3 phenotype, further extending the spectrum of abnormalities associated with GLIS3 mutations and providing novel insights into the role of GLIS3 in human physiological development. All but 2 of the patients within our cohort are still alive, and we describe the first patient to live to adulthood with a GLIS3 mutation, suggesting that even patients with a severe GLIS3 phenotype may have a longer life expectancy than originally described.
PDF
