Effect of the Synthetic Bile Salt Analog CamSA on the Hamster Model of Clostridium difficile Infection

Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea and has gained worldwide notoriety due to emerging hypervirulent strains and the high incidence of recurrence. We previously reported protection of mice from CDI using the antigerminant bile salt analog CamSA. Here we describe the effects of CamSA in the hamster model of CDI. CamSA treatment of hamsters showed no toxicity and did not affect the richness or diversity of gut microbiota; however, minor changes in community composition were observed. Treatment of C. difficile-challenged hamsters with CamSA doubled the mean time to death, compared to control hamsters. However, CamSA alone was insufficient to prevent CDI in hamsters. CamSA in conjunction with suboptimal concentrations of vancomycin led to complete protection from CDI in 70% of animals. Protected animals remained disease-free at least 30 days postchallenge and showed no signs of colonic tissue damage. In a delayed-treatment model of hamster CDI, CamSA was unable to prevent infection signs and death. These data support a putative model in which CamSA reduces the number of germinating C. difficile spores but does not keep all of the spores from germinating. Vancomycin halts division of any vegetative cells that are able to grow from spores that escape CamSA

Quality of life in children with primary antibody deficiency.

Primary antibody deficiency disorders (PADs) can have an excellent outlook if diagnosed early and treated appropriately, but require lifelong treatment with immunoglobulin replacement. Some carry risks of inflammatory complications even with optimal treatment. Quality of life (QoL) and the psychological impact of PADs has been relatively little studied, particularly in children. The purpose of this study was to evaluate QoL and psychological impact in a large group of children affected by a range of PADs, as well as a group with transient hypogammaglobulinemia of infancy (THI). Both parental and, where appropriate, child ratings, were collected using standardised questionnaires (PedsQL and SDQ). Higher rates of psychological difficulties, particularly emotional and peer-relationship difficulties were found in children with PAD when compared with healthy controls. Quality of life was poorer than in healthy controls, and also worse than in children affected by diabetes mellitus. Variations in QoL and the degree of psychological difficulties were found between specific diagnostic groups, with children affected by THI being amongst those with the lowest scores for QoL. Further studies are needed to corroborate and extend these findings, but this study confirms previous findings that primary antibody deficiency has a significant impact on quality of life and psychological well-being, and additionally suggests that the impact varies according to severity of the underlying condition. For those with significant difficulties psychological intervention at an early stage may be beneficial

In vivo killing of Staphylococcus aureus using a light-activated antimicrobial agent

Background: The widespread problem of antibiotic resistance in pathogens such as Staphylococcus aureus has prompted the search for new antimicrobial approaches. In this study we report for the first time the use of a light-activated antimicrobial agent, methylene blue, to kill an epidemic methicillin-resistant Staphylococcus aureus (EMRSA-16) strain in two mouse wound models.Results: Following irradiation of wounds with 360 J/cm(2) of laser light (670 nm) in the presence of 100 mu g/ml of methylene blue, a 25-fold reduction in the number of viable EMRSA was seen. This was independent of the increase in temperature of the wounds associated with the treatment. Histological examination of the wounds revealed no difference between the photodynamic therapy (PDT)-treated wounds and the untreated wounds, all of which showed the same degree of inflammatory infiltration at 24 hours.Conclusion: The results of this study demonstrate that PDT is effective at reducing the total number of viable EMRSA in a wound. This approach has promise as a means of treating wound infections caused by antibiotic-resistant microbes as well as for the elimination of such organisms from carriage sites

Hospitalisation following therapeutic community drug and alcohol treatment for young people with and without a history of criminal conviction

Introduction: This study examines the association between treatment in a therapeutic community for adolescents with drug and alcohol problems on hospitalisation outcomes up to 15 years later for all clients, and separately for those with and without a history of criminal conviction. Method: A quasi-experimental design was used to examine the linked administrative health and criminal justice records for all adolescents admitted to the Program for Adolescent Life Management (PALM) from January 2001 to December 2016 (n = 3059) in Sydney, Australia. ICD-10AM codes were used to designate hospitalisation outcomes as either physical injury, mental health problems, substance use disorders, or organic illness. The treatment and comparison groups were matched on factors associated with program retention, resulting in a final sample of 1266 clients. We examined the rate of hospitalisation up to 15 years posttreatment for all clients and stratified by prior conviction status using Cox regression analyses. Results: The treatment group had significantly lower rates of hospitalisation for a physical injury (HR = 0.77 [95% CI = 0.61–0.98]), mental health problem (HR = 0.62 [95% CI = 0.47–0.81]), substance use disorder (HR = 0.59 [95% CI = 0.47–0.75]), and organic illness (HR = 0.71 [95% CI = 0.55–0.92]). There was a significant interaction between treatment and prior criminal conviction status on rate of hospitalisation for physical injury, suggesting that the effect of treatment on physical injury was significantly greater for clients with a prior criminal conviction. Conclusions: Adolescents who engage in a therapeutic community treatment program may have a long-lasting reduction in the risk of subsequent hospitalisation. This also appears to apply to those with a history of criminal conviction

Effects of a peer-led Walking In ScHools intervention (the WISH study) on physical activity levels of adolescent girls: a cluster randomised pilot study.

School-based interventions may be effective at increasing levels of physical activity (PA) among adolescents; however, there is a paucity of evidence on whether walking can be successfully promoted to increase PA in this age group. This pilot study aimed to assess the effects of a 12-week school-based peer-led brisk walking programme on levels of school-time PA post intervention

Under a new light: validation of eddy covariance flux with light response functions of assimilation and estimates of heterotrophic soil respiration

Estimation of the basal or heterotrophic soil respiration is crucial for determination of whether an ecosystem is emitting or sequestering carbon. A severe bushfire in January 2014 at the Calperum flux tower, operational since August 2010, provided variation in ecosystem respiration and leaf area index as the ecosystem recovered. We propose ecosystem respiration is a function of leaf area index and the y-intercept is an estimate of heterotrophic soil respiration. We calculated an assimilation rate from eddy covariance data for light response functions to calculate ecosystem respiration incorporating suppression of the daytime autotrophic respiration. Ecosystem respiration from light response functions correlated with data processing calculations of ecosystem respiration by OzFluxQC (y0 = 0.161x + 0.0085; Adj. r2 = 0.698). The relationship between ecosystem respiration and leaf area index (y0 = 1.43x +0.398; Adj. r2 = 0.395) was also apparent. When this approach was compared to field measurements of soil respiration and mass balance calculations from destructive leaf area, leaf area index calculations and litter fall, the year of data corresponding to the year of soil respiration measurements, the y-intercept was 0.432 µmol m−2 s−1 or 163.44 gC m−2 year−1 (y0 = 1.37x + 0.432, Adj. r2 = 0.325). The mass balance approach for the net primary productivity when subtracted from the tower NEE estimated heterotrophic soil respiration of 134.59 gC m−2 year−1. This is only 28.9 gC different, therefore the y-intercept approach indeed provides an estimate of heterotrophic soil respiration.Georgia R. Koerber, Wayne S. Meyer, Qiaoqi SUN, Peter Cale, and Cacilia M. Ewen

Oral Contraceptive Pills Are Not a Risk Factor for Deep Vein Thrombosis or Pulmonary Embolism After Arthroscopic Shoulder Surgery

Background: Worldwide, more than 100 million women between the ages of 15 and 49 years take oral contraceptive pills (OCPs). OCP use increases the risk of venous thromboembolism (VTE) through its primary drug, ethinylestradiol, which slows liver metabolism, promotes tissue retention, and ultimately favors fibrinolysis inhibition and thrombosis. Purpose: To evaluate the effects of OCP use on VTE after arthroscopic shoulder surgery. Study Design: Cohort study; Level of evidence, 3. Methods: A large national payer database (PearlDiver) was queried for patients undergoing arthroscopic shoulder surgery. The incidence of VTE was evaluated in female patients taking OCPs and those not taking OCPs. A matched group was subsequently created to evaluate the incidence of VTE in similar patients with and without OCP use. Results: A total of 57,727 patients underwent arthroscopic shoulder surgery from 2007 to 2016, and 26,365 patients (45.7%) were female. At the time of surgery, 924 female patients (3.5%) were taking OCPs. The incidence of vascular thrombosis was 0.57% (n = 328) after arthroscopic shoulder surgery, and there was no significant difference in the rate of vascular thrombosis in male or female patients (0.57% vs 0.57%, respectively; P \u3e .99). The incidence of VTE in female patients taking and not taking OCPs was 0.22% and 0.57%, respectively (P = .2). In a matched-group analysis, no significant difference existed in VTE incidence between patients with versus without OCP use (0.22% vs 0.56%, respectively; P = .2). On multivariate analysis, hypertension (odds ratio [OR], 2.00; P \u3c .001) and obesity (OR, 1.43; P = .002) were risk factors for VTE. Conclusion: OCP use at the time of arthroscopic shoulder surgery is not associated with an increased risk of VTE. Obesity and hypertension are associated with a greater risk for thrombolic events, although the risk remains very low. Our findings suggest that patients taking OCPs should be managed according to the surgeon’s standard prophylaxis protocol for arthroscopic shoulder surgery

Select Biomarkers on the Day of Anterior Cruciate Ligament Reconstruction Predict Poor Patient-Reported Outcomes at 2-Year Follow-Up: A Pilot Study

Background. The majority of patients develop posttraumatic osteoarthritis within 15 years of anterior cruciate ligament (ACL) injury. Inflammatory and chondrodegenerative biomarkers have been associated with both pain and the progression of osteoarthritis; however, it remains unclear if preoperative biomarkers differ for patients with inferior postoperative outcomes. Hypothesis/Purpose. The purpose of this pilot study was to compare biomarkers collected on the day of ACL reconstruction between patients with good or poor 2-year postoperative outcomes. We hypothesized that inflammatory cytokines and chondrodegenerative biomarker concentrations would be significantly greater in patients with poorer outcomes. Study Design. Prospective cohort design. Methods. 22 patients (9 females, 13 males; age = 19.5 ± 4.1 years; BMI = 24.1 ± 3.6 kg/m2) previously enrolled in a randomized trial evaluating early anti-inflammatory treatment after ACL injury. Biomarkers of chondrodegeneration and inflammation were assessed from synovial fluid (sf) samples collected on the day of ACL reconstruction. Participants completed Knee Injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) questionnaires two years following surgery. Patients were then categorized based on whether their KOOS Quality of Life (QOL) score surpassed the Patient Acceptable Symptom State (PASS) threshold of 62.5 points or the IKDC PASS threshold of 75.9 points. Results. Patients that failed to reach the QOL PASS threshold after surgery (n = 6, 27%) had significantly greater sf interleukin-1 alpha (IL-1α; p = 0.004), IL-1 receptor antagonist (IL-1ra; p = 0.03), and matrix metalloproteinase-9 (MMP-9; p = 0.01) concentrations on the day of surgery. Patients that failed to reach the IKDC PASS threshold (n = 9, 41%) had significantly greater sf IL-1α (p = 0.02). Conclusion. These pilot data suggest that initial biochemical changes after injury may be an indicator of poor outcomes that are not mitigated by surgical stabilization alone. Biological adjuvant treatment in addition to ACL reconstruction may be beneficial; however, these data should be used for hypothesis generation and more definitive randomized clinical trials are necessary