Prospective clinical evaluation of a novel anatomic cuff for forearm crutches in patients with osteoarthritis.

The use of forearm crutches has been associated with pain and neuropraxia along the ulnar bone. Whilst anatomic grips have improved comfort of crutch walking, to date anatomic forearm cuffs have not been clinically evaluated. The aim of this clinical pilot study was to determine if the use of forearm crutches with anatomic cuffs reduces pain and increases comfort and function in long-term users of forearm crutches during a 4-week period. Prospective study in ten patients suffering from end-stage osteoarthritis of the lower extremity. All participants were long-term users of conventional forearm crutches. Participants used forearm crutches with an anatomically shaped cuff for 4-weeks. General health was assessed using the SF-36, and the crutches were evaluated using a newly developed questionnaire focusing on symptoms along the forearm. Pain and paresthesia along the forearms decreased by 3.3 points (95% confidence interval difference (CI): [-5.0; -1.6], p = .004) and 3.5 points (95%CI: [-5.1; -1.9], p = .002), respectively, after using the crutches with the new anatomic cuff for 4 weeks. Comfort and sense of security of crutch use increased by 3.0 points (95%CI: [1.3; 4.7], p = .007) and 2.4 points (95%CI: [0.7; 4.1], p = .024). Cross-correlation analysis revealed correlations among items in the same item category and no correlations between items of different item categories of the new questionnaires. An anatomically shaped cuff increases comfort of forearm crutches. Further research should confirm long-term clinical improvement. This study was registered retrospectively in ISRCTN (TRN: ISRCTN 11135150 ) on 14/02/2017

The inflammatory response of primary bovine mammary epithelial cells to Staphylococcus aureus strains is linked to the bacterial phenotype

Staphylococcus aureus is a major mastitis-causing pathogen in dairy cows. The latex agglutination-based Staphaurex test allows bovine S. aureus strains to be grouped into Staphaurex latex agglutination test (SLAT)-negative [SLAT(2)] and SLATpositive [SLAT(+)] isolates. Virulence and resistance gene profiles within SLAT(2) isolates are highly similar, but differ largely from those of SLAT(+) isolates. Notably, specific genetic changes in important virulence factors were detected in SLAT(2) isolates. Based on the molecular data, it is assumed that SLAT(+) strains are more virulent than SLAT(2) strains. The objective of this study was to investigate if SLAT(2) and SLAT(+) strains can differentially induce an immune response with regard to their adhesive capacity to epithelial cells in the mammary gland and in turn, could play a role in the course of mastitis. Primary bovine mammary epithelial cells (bMEC) were challenged with suspensions of heat inactivated SLAT(+) (n = 3) and SLAT(2) (n = 3) strains isolated from clinical bovine mastitis cases. After 1, 6, and 24 h, cells were harvested and mRNA expression of inflammatory mediators (TNF-a, IL-1b, IL-8, RANTES, SAA, lactoferrin, GM-CSF, COX-2, and TLR-2) was evaluated by reverse transcription and quantitative PCR. Transcription (DDCT) of most measured factors was induced in challenged bMEC for 6 and 24 h. Interestingly, relative mRNA levels were higher (P,0.05) in response to SLAT(+) compared to SLAT(2) strains. In addition, adhesion assays on bMEC also showed significant differences between SLAT(+) and SLAT(2) strains. The present study clearly shows that these two S. aureus strain types cause a differential immune response of bMEC and exhibit differences in their adhesion capacity in vitro. This could reflect differences in the severity of mastitis that the different strain types may induce

Healthy and diseased placental barrier on-a-chip models suitable for standardized studies

Pathologies associated with uteroplacental hypoxia, such as preeclampsia are among the leading causes of maternal and perinatal morbidity in the world. Its fundamental mechanisms are yet poorly understood due to a lack of good experimental models. Here we report an in vitro model of the placental barrier, based on co-culture of trophoblasts and endothelial cells against a collagen extracellular matrix in a microfluidic platform. The model yields a functional syncytium with barrier properties, polarization, secretion of relevant extracellular membrane components, thinning of the materno-fetal space, hormone secretion, and transporter function. The model is exposed to low oxygen conditions and perfusion flow is modulated to induce a pathological environment. This results in reduced barrier function, hormone secretion, and microvilli as well as an increased nuclei count, characteristics of preeclamptic placentas. The model is implemented in a titer plate-based microfluidic platform fully amenable to high-throughput screening. We thus believe this model could aid mechanistic understanding of preeclampsia and other placental pathologies associated with hypoxia/ischemia, as well as support future development of effective therapies through target and compound screening campaigns.Statement of Significance: The human placenta is a unique organ sustaining fetus growth but is also the source of severe pathologies, such as Preeclampsia. Though leading cause of perinatal mortality in the world, preeclampsia remains untreatable due to a lack of relevant in vitro placenta models. To better understand the pathology, we have developed 3D placental barrier models in a microfluidic device. The platform allows parallel culture of 40 perfused physiological miniaturized placental barriers, comprising a differentiated syncytium and endothelium that have been validated for transporter functions. Exposure to a hypoxic and ischemic environment enabled the mimicking of preeclamptic characteristics in high-throughput, which we believe could lead to a better understanding of the pathology as well as support future effective therapies development.</p

Wild type agr-negative livestock-associated MRSA exhibits high adhesive capacity to human and porcine cells

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of nosocomial infections and a major public health concern worldwide. During the last decade, MRSA of CC398 have emerged as important colonizers of livestock. These strains also represent an increasing cause of human infections. A recent study reporting a new dominant spa type among MRSA from Finish fattening pigs (CC398/t2741) identified a strain lacking both the global virulence regulator gene locus agr and the adhesion gene fnbB. The aim of this study was to characterize this agr/fnbB-negative livestock-associated MRSA strain in terms of growth, hemolysis and adhesive capacity, and to provide data on its genomic background. To this end, growth curves and hemolysis patterns were generated and adhesion assays on human keratinocyte and porcine nasal mucosa cell lines were performed. Whole genome sequencing was used to determine the nature and extent of the relevant deletions in the livestock strains. For comparison, an agr-positive, fnbB-negative CC398/t2741 strain from the same pig herd, an agr/fnbB- positive CC398/t034 strain from another pig herd and one human MRSA strain and its isogenic Δagr knockout mutant were used. The agr-negative strains adhered significantly better to human and porcine host cells than the agr-positive control strains. For the agr-positive porcine MRSA strains, cytotoxic effects on porcine mucosal cells were observed. The strong adhesive capacity of the naturally agr-negative livestock-associated MRSA, in combination with diminished cytotoxic effects, is likely favorable for inducing persistent colonization in pigs. Independently of the host cell type, similar adhesive capacities of the naturally agr-negative livestock-associated MRSA and the human MRSA strain were shown. Our results indicate that loss of agr in the livestock-associated MRSA strain investigated in this study may have increased its potential to be transmitted to and amongst humans

Regulatory measures against Erwinia amylovora in Switzerland

Switzerland joined the list of fireblight-affected European countries in 1989. Vigorous and systematic steps were taken to limit the impact of the disease on fruit production and amenity plants. These efforts are codified in a Swiss law detailing prevention, eradication, control measures and issues of compensation. As with many Swiss legal directives, there is a defined coordination of federal and cantonal responsibilities and, in the case of fireblight, there is also an emphasis at all levels on personal responsibility of owners of susceptible objects (e.g. nurseries, orchards, host plants). Extension activities have been a key component in achieving compliance with disease management regulations and in obtained public support for control efforts. Agroscope FAW Wädenswil has taken a leading role in this respect through its websit

Influence of the distribution and infection rates of psyllids on the vectoring ability of European stone fruit yellows in Switzerland

International audienceEuropean stone fruit yellows (ESFY) is caused by the phytoplasma ‘Candidatus Phytoplasma prunorum’, which is transmitted from plant to plant by insects of the genus Cacopsylla. Better knowledge of vector distribution in the orchards and on wild host plants is crucial for controlling the disease and preventing its spread. Cacopsylla pruni is known as the vector of ESFY. Recently, a second psyllid, Cacopsylla pinihiemata, has been identified as a vector; however, its vectoring capacity for ESFY phytoplasma is still unknown. The objective of this study was to map the distribution of psyllids in Switzerland and to determine the percentage of infested adults. The occurrence of psyllid species was monitored by sweeping techniques, and the percentage of infested adults was analyzed by nested PCR. Psyllid monitoring revealed that C. pruni is present in every Swiss region, with a similar population density in the different locations. In contrast, C. pinihiemata was only captured in Valais (southwest), the main apricot production area. This is probably due to the presence of specific conifers, which are the overwintering hosts for C. pinihiemata. Infested psyllid adults were found in half of the monitored regions. The percentage varied between 1.3 and 18.2% and was not higher in the apricot production area. Surprisingly, in 2013, ESFY infestation was only found in C. pruni and not in C. pinihiemata. However, in 2012, C. pinihiemata was also infested by ‘Ca. P. prunorum’. The capacity of the two psyllids in ESFY vectoring, their importance in ESFY epidemiology and the consequences on ESFY control strategies are discussed

Alcohol Biomarker Phosphatidylethanol as a Predictor of the Severity of Alcohol Withdrawal Syndrome.

AIMS to investigate the relationship between phosphatidylethanol (PEth) and withdrawal severity in patients with alcohol use disorder (AUD). METHODS in 34 patients with AUD admitted for treatment of acute alcohol withdrawal, data were available for initial blood PEth concentrations and scores throughout detoxification of symptoms of withdrawal assessed by trained medical staff using the alcohol withdrawal syndrome (AWS)-scale, a validated scale consisting of 11 items in the alcohol withdrawal syndrome (two subscales with seven physiological and five psychological symptoms). RESULTS a significant positive correlation between PEth and the severity of alcohol withdrawal was found. When the sample was divided into two groups, according to whether or not AWS score at some point in the treatment reached 6 or more, the median PEth score was higher in those whose peak score had been 6 or more (score of 6 being the suggested cutoff to start medicating the withdrawal syndrome). Although there was a trend for some aspects of the clinical history to be more 'severe' in those with higher AWS, no differences reached significance. CONCLUSION blood PEth on admission could have a role in identifying patients at risk of more severe AWS

Clemastine causes immune suppression through inhibition of extracellular signal-regulated kinase-dependent proinflammatory cytokines

BACKGROUND: Antihistamines are considered safe and used worldwide against allergy, pruritus, nausea, and cough and as sleeping aids. Nonetheless, a growing number of reports suggest that antihistamines also have immunoregulatory functions. OBJECTIVE: We examined the extent and by what potential mechanisms histamine-1-receptor (H1R) antagonists exert immune suppressive effects. METHODS: Immune suppression by antihistamines and immunosuppressants was tested in mice infected with Listeria monocytogenes. Potential modes of action were studied in vitro by using murine and human cells. We also tested whether injection of clemastine in healthy volunteers affected the activation of peripheral macrophages and monocytes. Finally, therapeutic application of clemastine-mediated immune suppression was tested in a murine model of sepsis. RESULTS: Clemastine and desloratadine strongly reduced innate responses to Listeria monocytogenes in mice as did dexamethasone. The immune suppression was MyD88 independent and characterized by inhibition of the mitogen-activated protein kinase-extracellular signal-regulated kinase signaling pathway, leading to overall impaired innate immunity with reduced TNF-α and IL-6 production. Surprisingly, the observed effects were H1R independent as demonstrated in H1R-deficient mice. Moreover, in a double-blind placebo-controlled clinical trial, 1 intravenous administration of clemastine reduced the TNF-α secretion potential of peripheral blood macrophages and monocytes. This inhibition could be exploited to treat sepsis in mice. CONCLUSIONS: The safety profile of antihistamines may need to be revisited. However, antihistamine-mediated immune suppression may also be exploited and find applications in the treatment of inflammatory diseases. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved