Intramuscular oxytocin versus Syntometrine® versus carbetocin for prevention of primary postpartum haemorrhage after vaginal birth: a randomised double-blinded clinical trial of effectiveness, side effects and quality of life.

OBJECTIVE: To compare intramuscular oxytocin, Syntometrine® and carbetocin for prevention of postpartum haemorrhage after vaginal birth. DESIGN: Randomised double-blinded clinical trial. SETTING: Six hospitals in England. POPULATION: A total of 5929 normotensive women having a singleton vaginal birth. METHODS: Randomisation when birth was imminent. MAIN OUTCOME MEASURES: Primary: use of additional uterotonic agents. Secondary: weighed blood loss, transfusion, manual removal of placenta, adverse effects, quality of life. RESULTS: Participants receiving additional uterotonics: 368 (19.5%) oxytocin, 298 (15.6%) Syntometrine and 364 (19.1%) carbetocin. When pairwise comparisons were made: women receiving carbetocin were significantly more likely to receive additional uterotonics than those receiving Syntometrine (odds ratio [OR] 1.28, 95% CI 1.08-1.51, P = 0.004); the difference between carbetocin and oxytocin was non-significant (P = 0.78); Participants receiving Syntometrine were significantly less likely to receive additional uterotonics than those receiving oxytocin (OR 0.75, 95% CI 0.65-0.91, P = 0.002). Non-inferiority between carbetocin and Syntometrine was not shown. Use of Syntometrine reduced non-drug PPH treatments compared with oxytocin (OR 0.64, 95% CI 0.42-0.97) but not carbetocin (P = 0.64). Rates of PPH and blood transfusion were not different. Syntometrine was associated with an increase in maternal adverse effects and reduced ability of the mother to bond with her baby. CONCLUSIONS: Non-inferiority of carbetocin to Syntometrine was not shown. Carbetocin is not significantly different to oxytocin for use of additional uterotonics. Use of Syntometrine reduced use of additional uterotonics and need for non-drug PPH treatments compared with oxytocin. Increased maternal adverse effects are a disadvantage of Syntometrine. TWEETABLE ABSTRACT: IM carbetocin does not reduce additional uterotonic use compared with IM Syntometrine or oxytocin.

One-year follow-up of the immune profile in serum and selected sites of generalized and localized aggressive periodontitis.

BACKGROUND: The local and systemic immunological profiles of important inflammatory mediators in the localized (LAgP) and generalized (GAgP) forms of aggressive periodontitis are still unknown, as well as the effect of periodontal therapy on these parameters. The aim of this prospective study was to evaluate clinical and immune responses of patients with AgP undergoing nonsurgical treatment. MATERIAL AND METHODS: Eighteen patients with GAgP, 10 with LAgP and 10 healthy participants were included in this study. AgP participants were submitted to scaling and root planing plus systemic antibiotics (amoxicillin and metronidazole). At baseline and 1-year follow-up were measured clinical parameters, such as probing depth [PD] and clinical attachment loss [CAL], and the levels of 10 immunological mediators (GM-CSF, M-CSF, MCP-1, ICAM-1, CXCL8, IL-1ß, TNF-α, IL-17, IL-4, and IL-10) in the gingival crevicular fluid (GCF) of selected sites [AgP forms: PD ≥ 6 mm or the deepest, bleeding on probing (BoP) and bone loss measured by periapical radiography; healthy individuals: PD ≤ 3 mm, no BoP, no bone loss] and serum. RESULTS: After periodontal treatment both forms of AgP presented a significant reduction of PD and CAL, an increase of GM-CSF, ICAM-1, MCP-1, TNF-α, IL-17, IL-4, and IL-10 in the GCF, as well as of GM-CSF and IL-4 in the serum, and a reduction in the serum concentration of IL-1ß. Serum levels of M-CSF, ICAM-1, and MCP-1 remained significantly below those found in healthy individuals in both forms of AgP even after therapy. An increase in the systemic or local levels of MCP-1, ICAM-1 and the anti-inflammatory profile (IL-4, IL-10) was correlated with an improvement in clinical parameters of LAgP patients. Also, a local reduction of IL-1ß levels in both forms of AgP was correlated with an increase in the clinical attachment gain. CONCLUSION: Nonsurgical periodontal therapy was successful in improving clinical parameters and modulating the immune response in both forms of AgP. However, this therapeutic approach does not seem to affect the deficient level of important serum mediators involved in mechanisms of cell transmigration.

Multicenter study to assess presenteeism in systemic lupus erythematosus and its relationship with clinical and sociodemographic features.

Objective The aim of this study was to measure presenteeism (productivity impairment while the patient is at work) and the related risk factors in patients with systemic lupus erythematosus (SLE) from Argentina. Methods A total of 130 consecutive (1997 American College of Rheumatology (ACR) criteria) working patients with SLE were assessed using a standardized data collection form. Sociodemographic, disease and work-related variables were collected. The Work Productivity and Activity Impairment (WPAI) questionnaire was performed. Results Overall, 130 patients were included in the analysis; 91% were women, and the mean age was 39 years (range 19-77). A total of 43% were White, 43% Mestizo and 13% Amerindian. Overall, 38% were single and 38% were married. A total of 75% had more than 12 years of formal education. The median disease duration was 7 years (interquartile range 25-75 (IQR) 4-13). Median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 0 (IQR 0-2), and median Systemic Lupus International Collaborating Clinics/ACR Damage Index (SLICC-SDI) score was 0 (IQR 0-1). Lupus quality of life (LupusQoL) domains scores were: physical health 87 (IQR 70-96), emotional health 78 (IQR 54-91), burden to others 75 (IQR 50-92), intimate relationships 87 (IQR 50-100), and body image 85 (IQR 70-100). Absenteeism was 8%, presenteeism was 19%, and overall work impairment (absenteeism + presenteeism) was 26%. In the multiple regression analysis, considering presenteeism as dependent variable, (adjusting by age, disease duration, >12 years of education, Non-white race, Visual Analogue Scale (VAS) pain, VAS fatigue, SLICC-SDI, LupusQoL, physical and emotional domains), we found that SLICC-SDI (odds ratio (OR) 1.68, confidence interval (CI) 1-2.7) and Non-white race (OR 3.27, CI 1.04-10) were related to presenteeism and >12 years of education (OR 0.30, CI 0.09-0.98) and higher scores of LupusQoL emotional health domain (OR 0.95, CI 0.92-0.98) were protective. Conclusions organ damage and Non-white race were significantly associated with presenteeism while >12 years of education and higher scores of LupusQoL emotional health domain were protective.

Effect of ultrasonic activation on the reduction of bacteria and endotoxins in root canals: a randomized clinical trial.

AIM: This randomized clinical trial aimed to compare the effectiveness of ultrasonic activation with that of nonactivated irrigation on the removal of bacteria and endotoxin from root canals. METHODOLOGY: Fifty patients with necrotic pulps and asymptomatic apical periodontitis were randomly allocated into two groups according to the final irrigation protocol after root canal preparation: Group UI - ultrasonic irrigation (n = 25) and Group NI - needle irrigation (n = 25). The root canals were medicated with calcium hydroxide for 14 days. Microbiological sampling was performed before (S1) and after the root canal preparation (S2), after the irrigation protocols (S3) and after the removal of the intracanal medication (S4). Total bacteria counts were determined by qPCR and the endotoxin levels by the limulus amebocyte lysate assay. Intragroup analyses were performed using the Wilcoxon test for related samples, whereas intergroup analyses were performed using the Mann-Whitney U-test (P < 0.05). RESULTS: All S1 samples were positive for bacteria, with median numbers of 1.49 × 106 and 8.55 × 105 bacterial cells for the UI and NI groups, respectively. This number significantly decreased in S2 samples (UI: 1.41 × 104 ; NI: 3.53 × 104 ; both with P < 0.001). After final irrigation protocols, there was a significant decrease in bacterial load from S2 to S3 samples in both groups (UI: 4.29 × 103 ; NI: 1.08 × 104 ; P < 0.01). Intergroup analysis revealed a significant difference between irrigation methods regarding bacterial counts in S3 samples (P < 0.05). In contrast, no significant differences were observed between groups for endotoxin levels (P > 0.05). CONCLUSIONS: Ultrasonic activation was more effective than nonactivated irrigation for reducing the number of bacteria but not the endotoxin levels in root canals of teeth with apical periodontitis.

Functionality and opposite roles of two interleukin 4 haplotypes in immune cells.

Cytokines expression can be influenced by polymorphisms in their respective coding genes. We associated the CTI/TTD haplotype (Hap-1) and TCI/CCI haplotype (Hap-2) in the IL4 gene formed by the -590, +33 and variable number of tandem repeat polymorphisms with the severity of chronic periodontitis in humans. The functionality of these IL4 haplotypes in the response of immune cells to phorbol 12-myristate 13-acetate (PMA) with Ionomycin and IL-1ß (as inflammatory stimuli) was evaluated. Gene expression (quantitative real-time PCR), profile of secreted cytokines (multiplex) and phenotypic polarization of T cells (flow cytometry) were the outcomes assessed. Green fluorescent protein reporter plasmid constructs containing specific IL4 haplotype were transiently transfected into JM cells to assess the influence of the individual haplotypes on promoter activity. In response to inflammatory stimuli the immune cells from Hap-1 haplotype had increased expression of anti-inflammatory IL4; conversely, the Hap-2 haplotype showed higher levels of pro-inflammatory cytokines. The haplotype CTI proved to be the most important for the regulation of IL4 promoter, regardless of the nature of the inflammatory stimulation; whereas the polymorphism in the promoter region had the least functional effect. In conclusion, IL4 haplotypes studied are functional and trigger opposite immune responses: anti-inflammatory (Hap-1) and pro-inflammatory (Hap-2). In addition, we identified the CTI haplotype as the main responsible for the regulation of IL4 transcriptional activity.

A comparison of the effects of medical Qigong and standard exercise therapy on symptoms and quality of life in patients with advanced cancer.

PURPOSE: Patients with advanced cancer frequently experience anxiety, depression and poor quality of life (QOL), as well as physical symptoms such as fatigue and weakness. Physical exercise has potential to help control these symptoms but the optimal training prescription is still not clear. We performed a study comparing medical Qigong (QG) and standard endurance and strength training (SET) in patients with advanced stage non-small cell lung (NSCLC) and gastrointestinal (GI) cancers. METHODS: A randomized, cross-over study was performed in patients with advanced NSCLC and GI cancers receiving or eligible for chemotherapy. Patients received supervised QG or SET twice-weekly for 6 weeks. Psychological functioning, QOL, symptoms and physical functioning were assessed before and after each intervention period. RESULTS: Nineteen patients completed both interventions. Comparing interventions revealed no difference between QG and SET on change in anxiety or depression scores or QOL. However, SET treatment was better at improving perceived strength (P = 0.05) and walking distance (P = 0.02). The order in which interventions were performed had a significant impact on the improvement in certain symptoms (sleep quality, breathlessness, P < 0.05), QOL (P = 0.01) and walking distance (P = 0.008). In all cases, the beneficial effects of the exercise interventions were markedly reduced during the second interval. CONCLUSIONS: QG and SET are equivalent in their impact on many aspects of psychological function in cancer patients. However, SET leads to greater improvements in exercise capacity and helps reduce some symptoms. The reduction in beneficial effect of SET on exercise function when offered as the second intervention is a new finding that warrants further study.

Micro-computed tomographic analysis of the radial geometry of intrarenal artery-vein pairs in rats and rabbits: Comparison with light microscopy.

We assessed the utility of synchrotron-radiation micro-computed tomography (micro-CT) for quantification of the radial geometry of the renal cortical vasculature. The kidneys of nine rats and six rabbits were perfusion fixed and the renal circulation filled with Microfil. In order to assess shrinkage of Microfil, rat kidneys were imaged at the Australian Synchrotron immediately upon tissue preparation and then post fixed in paraformaldehyde and reimaged 24 hours later. The Microfil shrank only 2-5% over the 24 hour period. All subsequent micro-CT imaging was completed within 24 hours of sample preparation. After micro-CT imaging, the kidneys were processed for histological analysis. In both rat and rabbit kidneys, vascular structures identified in histological sections could be identified in two-dimensional (2D) micro-CT images from the original kidney. Vascular morphology was similar in the two sets of images. Radial geometry quantified by manual analysis of 2D images from micro-CT was consistent with corresponding data generated by light microscopy. However, due to limited spatial resolution when imaging a whole organ using contrast-enhanced micro-CT, only arteries ≥100 and ≥60 µm in diameter, for the rat and rabbit respectively, could be assessed. We conclude that it is feasible and valid to use micro-CT to quantify vascular geometry of the renal cortical circulation in both the rat and rabbit. However, a combination of light microscopic and micro-CT approaches are required to evaluate the spatial relationships between intrarenal arteries and veins over an extensive range of vessel size.

Administration of Lactobacillus johnsonii FI9785 to chickens affects colonisation by Campylobacter jejuni and the intestinal microbiota.

1. Campylobacter jejuni is the most common bacterial cause of human food-borne gastroenteritis in the world. A major source of human infection is the consumption of contaminated meat, particularly poultry. New control measures to reduce or eliminate this pathogen from the animal gastrointestinal tract are urgently required, and the use of probiotics as competitive exclusion agents is a promising biocontrol measure to reduce C. jejuni in the food chain. 2. In this study, we assessed the potential of Lactobacillus johnsonii FI9785, which has shown efficacy against Clostridium perfringens, to combat C. jejuni. The effect of prophylactic administration of L. johnsonii on the ability of C. jejuni to colonise chickens was determined. 3. Two doses of L. johnsonii given a week apart led to a reduction in C. jejuni colonisation in the caecal contents, but this biocontrol seemed reliant upon a high level of initial colonisation by the probiotic. 4. The microbial composition in the chicken gut was significantly altered by the probiotic treatment, as shown by denaturing gradient gel electrophoresis of 16S rRNA gene amplicons. 5. Together these results demonstrate the potential of this probiotic strain to be tested further as a competitive exclusion agent in poultry against C. jejuni.

[Religious and cultural aspects of organ transplantation]. / Aspects religieux et culturels liés à la transplantation d'organes.

The number of transplantations is mainly limited by the shortage of organs, thereby leading to potentially lethal delays for patients registered on waiting lists. Among the causes of refusals of organ donation, religious reasons are often advocated. In order to make the point, we organized a debate between representatives of secularism ( " laïcité ") and of the most represented religions in Belgium, i.e. catholic, Islamic and Judaic. Even though the representation of death was variable, organ donation is authorized and even encouraged by the fundamental texts. Refusals of organ donation result more often from personal interpretations by local preachers. Therefore, the gathering of political and religious authorities in order to promote organ donation is desirable instead of sowing doubt for pseudo-religious reasons.

En médecine de transplantation, la pénurie d'organes représente le principal obstacle et cause de retard aux greffes vitales pour les receveurs inscrits sur liste d'attente. Parmi les causes de refus de don d'organes, des raisons d'ordre religieux sont souvent invoquées. Afin de faire le point sur cette problématique, nous avons organisé un débat rassemblant des représentants de la laïcité et des religions monothéistes les plus représentées en Belgique : catholicisme, islam, judaïsme. Il est apparu que, si la représentation de la mort varie selon les courants, le don d'organes est en fait autorisé, voire encouragé par les textes fondateurs des trois religions. Les refus sont plutôt le fait d'une interprétation personnelle par des prédicateurs. Dès lors, il serait judicieux de rassembler les forces politiques et spirituelles afin de promouvoir le don d'organes plutôt que de semer le doute à son sujet sous des prétextes pseudo-religieux.

RELN and VLDLR mutations underlie two distinguishable clinico-radiological phenotypes.

Pontocerebellar hypoplasias (PCH) are characterized by lack of development and/or early neurodegeneration of cerebellum and brainstem. We report five patients referred for PCH, showing atypical clinical and magnetic resonance imaging (MRI) features suggestive of defects in the Reelin pathway. We screened for mutations in RELN or VLDLR and compared the phenotype of these patients with that of previously reported patients. All patients had profound cerebellar hypoplasia on MRI with peculiar cerebellar morphology, associated with flattened pons and neocortical abnormalities. Patient 1 had profound motor and intellectual disability with moderate lissencephaly suggestive of RELN mutations and was shown to harbor a splicing homozygous RELN mutation. The four other patients had a milder phenotype consistent with CARMQ1 (cerebellar ataxia and mental retardation with or without quadrupedal locomotion). These patients showed mild simplification or thickening of cortical gyration and had VLDLR mutations. Reelin signaling regulates neuronal migration in the developing mammalian brain. VLDLR is a key component of the Reelin pathway. Our patients had a very small and dysplatic cerebellar vermis that should suggest the involvement of these genes. Moreover, differences in clinical severity, involvement of the cerebellar hemispheres, together with the severity of the neocortical defect, enables RELN-mutated patients to be distinguished from VLDLR-mutated patients.

Validation of an Argentine version of Lupus Quality of Life questionnaire.

OBJECTIVE: To determine reproducibility and validity of an Argentine version of the Lupus Quality of Life questionnaire (LupusQoL) and to determine cut-off values in the questionnaire. MATERIALS AND METHODS: One hundred and forty-seven systemic lupus erythematosus patients (American College of Rheumatology 1982/1997) were assessed from April 2014 to July 2014. Demographic and socioeconomic variables were collected, as well as SELENA/SLEDAI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index Score, comorbidities and treatment data. Patients completed LupusQoL-Argentine version and European Quality of Life Questionnaire (EuroQoL-5D). Internal consistency and reliability were examined. Convergent validity with EuroQoL-5D was assessed through analysis of latent classes, which established homogeneous categories from the responses of each domain of LupusQoL and for the total. RESULTS: Out of 147 patients, 93.2% were female, mean age 36.4 ± 11.1 years, mean disease duration 2.7 ± 9 years, mean SELENA/SLEDAI 2.7 ± 3 points. The cut-off point that defined good or bad quality of life was 0.739 for EuroQoL 5D and 63 for LupusQoL. Cut-off values for each LupusQoL domain were also defined, creating two classes in each of them. There was moderate to high concordance to classify quality of life (Kappa = 0.74, 95% confidence interval = 0.54, 0.95). CONCLUSION: The Argentine version of LupusQoL is a valid, reliable and reproducible instrument to assess quality of life. In this study, cut-off points that allow the classification of patients regarding whether they have good or bad quality of life are established for the first time.

[Differences in the Provision of Lifestyle Counseling for Cardiovascular Disease Prevention Between Urban and Rural Regions in Germany. Findings from a National Survey of Primary Care Physicians]. / Stadt-Land-Unterschiede im Angebot von Lebensstilberatung zur Prävention kardiovaskulärer Erkrankungen in der Hausarztpraxis. Ergebnisse einer bundesweiten Hausärztebefragung.

AIMS: In Germany, shortages in primary care physicians (PCPs) were reported in some rural regions. In this paper, we explored if regional differences in the distribution of PCPs are associated with the provision of lifestyle counseling in primary care. METHODS: In a nationwide study, a total of 4,074 randomly selected PCPs were asked about provision of lifestyle counseling to their patients, their attitudes, and perceived barriers. RESULTS: PCPs from rural regions provided less frequently lifestyle advice for cardiovascular disease prevention. Compared to their colleagues in urban areas, more PCPs from rural regions believed that were inadequately qualified for the lifestyle counseling and that they had been less successful in helping patients to modify their lifestyles. Physicians from rural practices named more often than PCPs from urban practices a lack of adherence by the patients (65 vs. 57%), insufficient opportunities to collaborate with providers of preventive services (62 vs. 55%), and lack of time (66 vs. 52%; all p<0.001) as barriers in providing patients with lifestyle counseling. CONCLUSION: Taking into account the expected increased shortages in PCPs in rural regions, the results show the need for targeted interventions for improving lifestyle counseling in rural practices.

The effect of conventional mechanical periodontal treatment on red complex microorganisms and clinical parameters in Down syndrome periodontitis patients: a pilot study.

Periodontal disease (PD) is induced by a complex microbiota, such as Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola (together called the red complex), which triggers intense inflammatory reaction. Down syndrome (DS) individuals demonstrate a high prevalence of PD compared with those who are otherwise chromosomally normal (euploids). This pilot study aimed to evaluate the effect of non-surgical periodontal treatment in DS chronic periodontitis patients on clinical and microbiological parameters. Patients with chronic periodontitis, 23 DS and 12 euploids (control group), were submitted to non-surgical mechanical periodontal treatment, followed by maintenance for 45 days. Clinical parameters after periodontal treatment were similar in diseased and healthy sites, independent of the genetic background. Diseased sites of DS and control patients harbored similar levels of P. gingivalis and T. forsythia at baseline, but significantly higher levels of T. denticola were found in DS patients. Increased levels of P. gingivalis at healthy sites were found in DS individuals. Non-surgical periodontal therapy decreased the levels of red complex microorganisms and improved the tested clinical parameters of diseased sites in both groups. However, the levels of red complex bacteria were higher in diseased sites of DS patients after the periodontal treatment. We conclude in this pilot study that, although the mechanical periodontal treatment seemed to be effective in DS subjects over a short-term period, the red complex bacteria levels did not decrease significantly in diseased sites, as occurred in controls. Therefore, for DS patients, it seems that the conventional non-surgical periodontal therapy should be improved by utilizing adjuvants to reduce the presence of periodontopathogens.

Long-term survivor characteristics in HER2-positive metastatic breast cancer from registHER.

BACKGROUND: Data characterising long-term survivors (LTS) with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) are limited. This analysis describes LTS using registHER observational study data. METHODS: A latent class modelling (LCM) approach was used to identify distinct homogenous patient groups (or classes) based on progression-free survival (PFS), overall survival, and complete response. Demographics, clinicopathologic factors, first-line treatment patterns, and clinical outcomes were described for each class. Class-associated factors were evaluated using logistic regression analysis. RESULTS: LCM identified two survivor groups labelled as LTS (n=244) and short-term survivors (STS; n=757). Baseline characteristics were similar between groups, although LTS were more likely to be white (83.6% vs 77.8%) with oestrogen receptor-positive (ER+) or progesterone receptor-positive (PgR+) disease (59.4% vs 50.9%). Median PFS in LTS was 37.2 (95% confidence interval (CI): 32.9-40.5) vs 7.3 months (95% CI: 6.8-8.0) in STS. Factors associated with long-term survival included ER+ or PgR+ disease, metastasis to node/local sites, first-line trastuzumab use, and first-line taxane use. CONCLUSIONS: Prognostic variables identified by LCM define a HER2-positive MBC patient profile and therapies that may be associated with more favourable long-term outcomes, enabling treatment selection appropriate to the patient's disease characteristics.

Microbial composition of atherosclerotic plaques.

OBJECTIVE: The association of infections such as periodontitis with atherosclerotic diseases is well documented. In spite of the high diversity of the human oral microbiota, and its close contact with the circulatory system, few oral species were detected in atherosclerotic plaques. Thus, we attempted to evaluate the microbial diversity of atherosclerotic plaques from patients with different periodontal conditions, submitted to endarterectomy by a broad-range microbial method. MATERIALS AND METHODS: Patients indicated for aorta endarterectomy due to myocardial infarction were recruited for periodontal clinical examination. The microbial diversity of atherosclerotic plaques (n = 35) was evaluated by sequence analysis of bacterial 16S rRNA libraries. RESULTS: Bacterial DNA was detected in 12 endarterectomy specimens (34.3%). Twenty-three bacterial species/phylotypes were identified. Proteobacteria and Firmicutes comprised 78.3% and 21.7% of the identified taxa, respectively. Fifteen (60.9%) phylotypes were reported as yet uncultivable or as yet uncharacterized species. Two uncultured phylotypes were previously detected in the human mouth. The periodontopathogen Aggregatibacter actinomycetemcomitans was detected in seven samples (20%), followed by Pseudomonas species. There was no association between periodontal parameters and detection of A. actinomycetemcomitans or other phylotypes in atherosclerotic plaques. CONCLUSION: Our results suggest a role of the oral microbiota in the development of inflammation in atherogenesis, particularly of A. actinomycetemcomitans.

Application of Lactobacillus johnsonii expressing phage endolysin for control of Clostridium perfringens.

Clostridium perfringens is frequently found in food and the environment and produces potent toxins that have a negative impact on both human and animal health and particularly on the poultry industry. Lactobacillus johnsonii FI9785, isolated from the chicken gastrointestinal tract, has been demonstrated to exclude Cl. perfringens in poultry. We have investigated the interaction of wild-type Lact. johnsonii FI9785 or an engineered strain expressing a cell wall-hydrolysing endolysin with Cl. perfringens in vitro, using a batch culture designed to simulate human gastrointestinal tract conditions. Co-culture experiments indicated that acid production by Lact. johnsonii is important in pathogen control. The co-culture of the endolysin-secreting Lact. johnsonii with Cl. perfringens showed that the engineered strain had the potential to control the pathogen, but the ability to reduce Cl. perfringens numbers was not consistent. Results obtained indicate that survival of high numbers of Lact. johnsonii will be essential for effective pathogen control. Significance and impact of the study: The bacterium Lactobacillus johnsonii FI9785 reduces numbers of the pathogen Clostridium perfringens in vitro. Biocontrol was improved by engineering the strain to produce and export a cell wall-hydrolysing endolysin, but good survival of the producer strain is essential. The production of bacteriophage endolysins by commensal bacteria has the potential to improve competitive exclusion of pathogens in the gastrointestinal tract.

Recurrence after primary salivary gland carcinoma: Frequency, survival, and risk factors.

BACKGROUND: Primary salivary gland carcinomas (SGC) are rare neoplasms that present therapeutic challenges especially in recurrent tumors. The aim of this study was to investigate the incidence and distribution of tumor recurrence, associated risk factors, and survival. METHODS: This analysis includes data from 318 patients treated for SGC between 1992 and 2020. Survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate analyses were used to identify risk factors associated with recurrence. RESULTS: 21.7% of the patients developed recurrent disease after a mean of 38.2 months. In multivariate analysis, positive-resection margins, vascular invasion, and tumor localization in the submandibular gland and small salivary glands were independent factors for recurrence. The 5-year overall survival was 67%, the 5-year disease-free survival was 54%. CONCLUSION: Tumor recurrence in SGC occurred in one out of five patients. In highly aggressive entities and patients with risk factors, treatment intensification should be considered.

Strongly reduced penetration of atomic deuterium in radiation-damaged tungsten.

Radiation-damaged tungsten is exposed to high-flux, low-energy deuterium plasmas at self-bias conditions. We observe that the fraction of deuterium that penetrates is only 10(-5)-10(-7) of the plasma flux and strongly dependent on the local surface temperature. We propose that deuterium does not directly penetrate bulk tungsten but that it thermalizes at the surface, where it forms a protective chemisorbed layer. We find an energy barrier of 1-2 eV between the surface and bulk, causing the influx of deuterium to be low as compared to the number of defects and leading to slow filling of the damaged layer.

Farm-derived Gram-positive bacterium Staphylococcus sciuri W620 prevents asthma phenotype in HDM- and OVA-exposed mice.

BACKGROUND: Farm-derived dust samples have been screened for bacteria with potential allergo-protective properties. Among those was Staphylococcus sciuri W620 (S. sciuri W620), which we tested with regard to its protective capacities in murine models of allergic airway inflammation. METHODS: We employed two protocols of acute airway inflammation in mice administering either ovalbumin (OVA) or house dust mite extract (HDM) for sensitization. Mechanistic studies on the activation of innate immune responses to S. sciuri W620 were carried out using human primary monocytic dendritic cells (moDC) and co-culture with autologous T cells. RESULTS: The allergo-protective properties of S. sciuri W620 were proven in a T(H)2-driven OVA model as well as in a mixed T(H)1/T(H)2 phenotype HDM model as demonstrated by abrogation of eosinophils and neutrophils in the airways after intranasal treatment. In the HDM model, lymph node cell T(H)1/T(H)2 signature cytokines were decreased in parallel. Studies on human moDC revealed an activation of TLR2 and NOD2 receptors and initiation of DC maturation following incubation with S. sciuri W620. Cytokine expression analyses after exposure to S. sciuri W620 showed a lack of IL-12 production in moDC due to missing transcription of the IL-12p35 mRNA. However, such DC selectively supported T(H)1 cytokine release by co-cultured T cells. CONCLUSION AND CLINICAL RELEVANCE: Our proof-of-concept experiments verify the screening system of farm-derived dust samples as suitable to elucidate new candidates for allergo-protection. S. sciuri W620 was shown to possess preventive properties on airway inflammation providing the basis for further mechanistic studies and potential clinical implication.