An Integrated Smart Pond Water Quality Monitoring and Fish Farming Recommendation Aquabot System.

The integration of cutting-edge technologies such as the Internet of Things (IoT), robotics, and machine learning (ML) has the potential to significantly enhance the productivity and profitability of traditional fish farming. Farmers using traditional fish farming methods incur enormous economic costs owing to labor-intensive schedule monitoring and care, illnesses, and sudden fish deaths. Another ongoing issue is automated fish species recommendation based on water quality. On the one hand, the effective monitoring of abrupt changes in water quality may minimize the daily operating costs and boost fish productivity, while an accurate automatic fish recommender may aid the farmer in selecting profitable fish species for farming. In this paper, we present AquaBot, an IoT-based system that can automatically collect, monitor, and evaluate the water quality and recommend appropriate fish to farm depending on the values of various water quality indicators. A mobile robot has been designed to collect parameter values such as the pH, temperature, and turbidity from all around the pond. To facilitate monitoring, we have developed web and mobile interfaces. For the analysis and recommendation of suitable fish based on water quality, we have trained and tested several ML algorithms, such as the proposed custom ensemble model, random forest (RF), support vector machine (SVM), decision tree (DT), K-nearest neighbor (KNN), logistic regression (LR), bagging, boosting, and stacking, on a real-time pond water dataset. The dataset has been preprocessed with feature scaling and dataset balancing. We have evaluated the algorithms based on several performance metrics. In our experiment, our proposed ensemble model has delivered the best result, with 94% accuracy, 94% precision, 94% recall, a 94% F1-score, 93% MCC, and the best AUC score for multi-class classification. Finally, we have deployed the best-performing model in a web interface to provide cultivators with recommendations for suitable fish farming. Our proposed system is projected to not only boost production and save money but also reduce the time and intensity of the producer's manual labor.

Characteristics of papers that affect citations in the Journal of Fish Biology.

Identifying the factors that influence the citation of articles helps authors improve the impact and reach of their research. Analysis of publications in the Journal of Fish Biology between 2008 and 2021 revealed that variables such as the number of keywords, abstract length, number of authors, and page length were associated with higher impact papers. These trends applied to both review and regular papers. These findings suggest that papers that are more informative, have higher numbers of authors, and have more keywords are more likely to be cited. Adoption of some simple "best-practice" behaviors can improve the likelihood that a paper is cited.

TAKEN: A Traffic Knowledge-Based Navigation System for Connected and Autonomous Vehicles.

Connected and autonomous vehicles (CAVs) have witnessed significant attention from industries, and academia for research and developments towards the on-road realisation of the technology. State-of-the-art CAVs utilise existing navigation systems for mobility and travel path planning. However, reliable connectivity to navigation systems is not guaranteed, particularly in urban road traffic environments with high-rise buildings, nearby roads and multi-level flyovers. In this connection, this paper presents TAKEN-Traffic Knowledge-based Navigation for enabling CAVs in urban road traffic environments. A traffic analysis model is proposed for mining the sensor-oriented traffic data to generate a precise navigation path for the vehicle. A knowledge-sharing method is developed for collecting and generating new traffic knowledge from on-road vehicles. CAVs navigation is executed using the information enabled by traffic knowledge and analysis. The experimental performance evaluation results attest to the benefits of TAKEN in the precise navigation of CAVs in urban traffic environments.

Treatment-related fertility impairment in long-term female childhood, adolescent and young adult cancer survivors: investigating dose-effect relationships in a European case-control study (PanCareLIFE).

STUDY QUESTION: Which chemotherapeutic agents and body site-specific radiation fields are dose-dependently associated with an increased risk of fertility impairment in long-term female childhood, adolescent and young adulthood (CAYA) cancer survivors? SUMMARY ANSWER: Busulfan, lower abdominal radiotherapy (RT) and total body irradiation (TBI) seem to be associated with fertility impairment at any dose, whereas gonadotoxicity of melphalan and procarbazine is suggested at medium/high (>140 mg/m2) or high dose (>5600 mg/m2) therapy, respectively. WHAT IS KNOWN ALREADY: Several treatment-related fertility deficits, as assessed by both self-reported outcomes and hormonal markers are known to occur following treatment of CAYA cancer. However, knowledge regarding precise dose-related estimates of these treatment-related risks are scarce. STUDY DESIGN, SIZE, DURATION: The current case-control study was nested within the PanCareLIFE cohort study. In total, 1332 CAYA survivors from 8 countries, 9 institutions and 11 cohorts, participated in and contributed data to the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: All participants were female 5-year CAYA cancer survivors. In total, 450 cases (fertility impaired survivors) and 882 matched controls (not fertility impaired survivors) were included. Fertility impairment was defined using both questionnaire data (primary or secondary amenorrhea; use of artificial reproductive techniques; unfulfilled wish to conceive) and hormonal data (FSH and anti-Müllerian hormone (AMH)). Multivariable logistic regression models were used to investigate the effect of (i) alkylating agent exposure, and (ii) dose categories for individual chemotherapeutic agents and for RT-exposed body sites. MAIN RESULTS AND THE ROLE OF CHANCE: A positive dose-effect relationship between cyclophosphamide equivalent dose (CED) score and fertility impairment was found, with survivors with a CED score > 7121 mg/m2 being at a significantly increased risk of fertility impairment (odds ratio (95% CI) = 2.6 (1.9-3.6) P < 0.001). Moreover, cumulative dose variables of the following treatments were significantly associated with fertility impairment: busulfan, carmustine, cyclophosphamide, melphalan, procarbazine, lower abdominal RT and TBI. Busulfan, lower abdominal RT and TBI seem to be associated with fertility impairment at any dose, whereas gonadotoxicity of melphalan and procarbazine is suggested at medium/high (>140 mg/m2) or high dose (>5600 mg/m2) therapy, respectively. LIMITATIONS, REASONS FOR CAUTION: Our study may have been subject to selection bias since data from about half of the original base cohorts were available for the current study. This could impact the generalizability of our study results. WIDER IMPLICATIONS OF THE FINDINGS: We identified survivors at high risk for fertility impairment and, consequently, for a reduced or even absent reproductive life span. Both girls and young women who are about to start anti-cancer treatment, as well as adult female survivors, should be counselled about future parenthood and referred to a reproductive specialist for fertility preservation, if desired. STUDY FUNDING/COMPETING INTEREST(S): This study has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602030. There are no competing interests. TRIAL REGISTRATION NUMBER: n/a.

Prevalence of insulin as a first-line therapy and associated factors in people with type 2 diabetes in German primary care practices.

AIM: To evaluate how many people with type 2 diabetes receive a treatment regimen with insulin as a first-line therapy and the factors associated with this. METHODS: This retrospective study was based on data from the Disease Analyzer database and included 10 497 people with type 2 diabetes with an initial prescription of anti-hyperglycaemic therapy from 859 general and diabetologist practices in Germany between January 2014 and December 2018. The main outcome of the study was the prevalence of insulin as a first-line therapy. A multivariable logistic regression model was performed to investigate the association between predefined variables and the probability of receiving insulin as a first-line therapy. RESULTS: A total of 7.1% of participants received insulin as a first-line therapy. Diabetologist practice [odds ratio (OR) 2.71, 95% confidence interval (CI) 1.81-4.06], age > 80 years (OR 2.35, 95% CI 1.20-4.61) compared with age ≤ 40 years, HbA1c ≥ 86 mmol/mol (10%) (OR 2.99, 95% CI 1.81-4.95) compared with HbA1c < 48 mmol/mol (6.5%), renal complications (OR 1.91, 95% CI 1.29-2.81), peripheral artery disease (OR 1.94, 95% CI 1.30-2.81), neurological complications (OR 1.45, 95% CI 1.00-2.09), Charlson Comorbidity Index (OR 1.16, 95% CI 1.08-1.25) and higher number of different drugs prescribed within 12 months prior-the index date (OR 1.09, 95% CI 1.05-1.12) were significantly associated with the probability of receiving insulin as a first-line therapy. CONCLUSION: Insulin is rarely used as a first-line therapy in people with type 2 diabetes. Furthermore, a person's likelihood of receiving insulin as a first-line therapy is significantly influenced by diabetologist practice, age, HbA1c ≥ 86 mmol/mol (10%), renal, neurological and vascular complications, higher multimorbidity, and polypharmacy.

[Remarkable medical advances in rheumatology : may be ]. / Une révolution thérapeutique en rhumatologie : oui, mais .

The development of new drugs is a significant activity in a university hospital that favors access to therapeutic novelties to patients. Rheumatology, whose drug armamentarium was poor in the 1980s, has benefited from the huge progresses of immunology in the 1980-1990s, allowing a therapeutic revolution in whom the academic hospital of Liège (CHU Liège) has been strongly implicated. First protocols with anti-TNF-? monoclonal antibodies have been applied in 1997. Sixty-one protocols have been initiated in rheumatoid arthritis, 12 in ankylosing spondylitis, 10 in psoriatic arthritis, 9 in systemic erythematosus lupus, 3 in giant cell arteritis, 1 in polymyalgia rheumatica, 5 in osteoarthritis and 4 in osteoporosis. Potential and pitfalls will be discussed disease by disease and also by drug categories. The balance remains globally positive, but remission is far from be reached.

La recherche clinique médicamenteuse est une activité importante dans un hôpital universitaire. Elle valide des nouveautés thérapeutiques et fait bénéficier les patients de traitements novateurs bien avant leur mise sur le marché. La rhumatologie est une discipline dont l'arsenal thérapeutique était pauvre dans les années 1980, et les immenses progrès de l'immunologie, réalisés entre 1980 et 1995, lui ont permis de vivre une véritable révolution thérapeutique à laquelle notre service a amplement participé. C'est en 1997 que les premiers traitements par anticorps monoclonaux anti-TNF-? (les traitements dits biologiques) ont été utilisés au CHU de Liège. Soixante et une études seront initiées dans la polyarthrite rhumatoïde, 12 dans la spondylarthrite ankylosante, 10 dans la polyarthrite psoriasique, 9 dans le lupus érythémateux disséminé, 3 dans l'artérite temporale de Horton, une dans la pseudopolyarthrite rhizomélique, une dans la sclérodermie, 5 dans l'arthrose, 4 dans l'ostéoporose. Les espoirs et les déceptions observées dans les différentes indications, et avec les différentes molécules, sont analysées. Le bilan est globalement positif, mais les résultats encore insuffisants que pour arriver au concept de rémission.

PPARγ Regulates Mitochondrial Structure and Function and Human Pulmonary Artery Smooth Muscle Cell Proliferation.

Pulmonary hypertension (PH) is a progressive disorder that causes significant morbidity and mortality despite existing therapies. PH pathogenesis is characterized by metabolic derangements that increase pulmonary artery smooth muscle cell (PASMC) proliferation and vascular remodeling. PH-associated decreases in peroxisome proliferator-activated receptor γ (PPARγ) stimulate PASMC proliferation, and PPARγ in coordination with PPARγ coactivator 1α (PGC1α) regulates mitochondrial gene expression and biogenesis. To further examine the impact of decreases in PPARγ expression on human PASMC (HPASMC) mitochondrial function, we hypothesized that depletion of either PPARγ or PGC1α perturbs mitochondrial structure and function to stimulate PASMC proliferation. To test this hypothesis, HPASMCs were exposed to hypoxia and treated pharmacologically with the PPARγ antagonist GW9662 or with siRNA against PPARγ or PGC1α for 72 hours. HPASMC proliferation (cell counting), target mRNA levels (qRT-PCR), target protein levels (Western blotting), mitochondria-derived H2O2 (confocal immunofluorescence), mitochondrial mass and fragmentation, and mitochondrial bioenergetic profiling were determined. Hypoxia or knockdown of either PPARγ or PGC1α increased HPASMC proliferation, enhanced mitochondria-derived H2O2, decreased mitochondrial mass, stimulated mitochondrial fragmentation, and impaired mitochondrial bioenergetics. Taken together, these findings provide novel evidence that loss of PPARγ diminishes PGC1α and stimulates derangements in mitochondrial structure and function that cause PASMC proliferation. Overexpression of PGC1α reversed hypoxia-induced HPASMC derangements. This study identifies additional mechanistic underpinnings of PH, and provides support for the notion of activating PPARγ as a novel therapeutic strategy in PH.

Correction to: Inflammatory markers before and after farrowing in healthy sows and in sows affected with postpartum dysgalactia syndrome.

The original article [1] contains an error whereby the caption in Figure 8 is incorrect; the correct caption can be seen ahead alongside its respective image.

Development of a genetic sexing strain of Anopheles arabiensis for KwaZulu-Natal, South Africa.

An efficient sexing system is important for the release of sterile males for any control programme using the sterile insect technique. This study describes the development and characterization of a new genetic sexing strain from South Africa (GMK), needed for the planned implementation of such a programme in northern KwaZulu-Natal Province. The base colony used was a locally modified laboratory strain of Anopheles arabiensis containing a sex-linked gene conferring dieldrin resistance to male mosquitoes. Female A. arabiensis mosquitoes from northern KwaZulu-Natal were mated with these males and backcrossed to introduce the dieldrin resistance gene to the Y chromosome. The resulting strain therefore had an overall genotype representing the local population but with the Y chromosome containing the dieldrin resistance gene. Life-history characteristics, stability of the sex-linked resistance marker, and reduction in dieldrin waste were investigated. The strain showed semi-sterility exhibited by low egg hatch rates, faster development in the immature stages and longer adult survivorship compared with the parental strains. While the GMK strain carrying the dieldrin-resistant gene was successfully established, the stability of the gene is limited, requiring periodic purification. Dieldrin waste can be limited by treating many more eggs than currently recommended.

[Treatment of femoral shaft fractures in children and adolescents ≥50 kg : A retrospective multicenter trial]. / Behandlung der Femurschaftfraktur bei Kindern und Jugendlichen mit einem Körpergewicht ≥50 kg : Eine retrospektive multizentrische Erhebung.

BACKGROUND: Operative treatment of diaphyseal fractures of the femur in older children and adolescents remains controversial due to multiple surgical options and higher complication rates in single-center studies compared to younger children. This retrospective multicenter study aimed to register early and late complications in day-by-day treatment. MATERIAL AND METHODS: Sixteen hospitals with particular expertise in pediatric orthopedic trauma participated in this study. Patients with diaphyseal femur fractures, a body weight ≥50 kg (aged 10-16 years) and treated between 2008 and 2012 were included. Age, weight, fracture type, and choice of operative treatment were correlated to complication rate and type. Patients with pathologic fractures and/or metabolic bone disorders were excluded. RESULTS: Fifty-three children (15 females and 38 males; mean age: 14.2 y [SD 1.4 y]; mean body weight: 60.5 kg [max. 95 kg]) with 54 fractures were included. Elastic stable intramedullary nailing (ESIN) was the treatment of choice in 31 of 42 fractures with open growth plates. In the subgroup with two nails, 7 of 12 patients experienced revision surgery due to instability or shortening. Three patients with ESIN and end caps had no complications. In the subgroup with three inserted nails (11 patients), one patient was converted to external fixation. Nine patients received primary or secondary plate osteosyntheses. Within this group, two patients had deep infections; one implant failure, and one peri-implant fracture were recorded. Adolescent lateral femoral nailing (ALFN), when used as the primary treatment option in two patients, was free of complications. When used as a secondary treatment option in three patients, one patient had a pseudarthrosis and one an infection. Both were treated in further operative procedures. In a group of eight patients with closed physes, regular intramedullary nailing as primary or secondary treatment of choice resulted in one locking screw change. As late complications, leg length discrepancy (LLD) over 15 mm (n = 2) and loss of range of motion (ROM) (n = 4; two knee and three hip) were noted in patients receiving multiple revisions or serious postoperative complication. CONCLUSIONS: Children older than 10 years of age with a body weight ≥50 kg and open physes are prone to complications regardless of treatment choice. A smaller revision rate occurred in patients treated with ESIN and end caps or a third nail compared to the other treatment options. When physes are closed, rigid intramedullary nailing is the treatment of choice.

Hypoxia inhibits expression and function of mitochondrial thioredoxin 2 to promote pulmonary hypertension.

Pulmonary hypertension (PH) is characterized by increased pulmonary vascular resistance, pulmonary vascular remodeling, and increased pulmonary vascular pressures that often result in right ventricular dysfunction, leading to right heart failure. Evidence suggests that reactive oxygen species (ROS) contribute to PH pathogenesis by altering pulmonary vascular cell proliferation and intracellular signaling pathways. However, the role of mitochondrial antioxidants and oxidant-derived stress signaling in the development of hypoxia-induced PH is largely unknown. Therefore, we examined the role of the major mitochondrial redox regulator thioredoxin 2 (Trx2). Levels of Trx2 mRNA and protein were examined in human pulmonary arterial endothelial cells (HPAECs) and smooth muscle cells (HPASMCs) exposed to hypoxia, a common stimulus for PH, for 72 h. Hypoxia decreased Trx2 mRNA and protein levels. In vitro overexpression of Trx2 reduced hypoxia-induced H2O2 production. The effects of increased Trx2 protein level were examined in transgenic mice expressing human Trx2 (TghTrx2) that were exposed to hypoxia (10% O2) for 3 wk. TghTrx2 mice exposed to hypoxia had exacerbated increases in right ventricular systolic pressures, right ventricular hypertrophy, and increased ROS in the lung tissue. Trx2 overexpression did not attenuate hypoxia-induced increases in Trx2 oxidation or Nox4 expression. Expression of a dominant negative C93S Trx2 mutant that mimics Trx2 oxidation exacerbated hypoxia-induced increases in HPASMC H2O2 levels and cell proliferation. In conclusion, Trx2 overexpression failed to attenuate hypoxia-induced HPASMC proliferation in vitro or hypoxia-induced PH in vivo. These findings indicate that strategies to enhance Trx2 expression are unlikely to exert therapeutic effects in PH pathogenesis.

Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation.

Serine proteinase inhibitor, clade E, member 2 (SERPINE2), is a cell- and extracellular matrix-associated inhibitor of thrombin. Although SERPINE2 is a candidate susceptibility gene for chronic obstructive pulmonary disease, the physiologic role of this protease inhibitor in lung development and homeostasis is unknown. We observed spontaneous monocytic-cell infiltration in the lungs of Serpine2-deficient (SE2(-/-)) mice, beginning at or before the time of lung maturity, which resulted in lesions that resembled bronchus-associated lymphoid tissue (BALT). The initiation of lymphocyte accumulation in the lungs of SE2(-/-) mice involved the excessive expression of chemokines, cytokines, and adhesion molecules that are essential for BALT induction, organization, and maintenance. BALT-like lesion formation in the lungs of SE2(-/-) mice was also associated with a significant increase in the activation of thrombin, a recognized target of SE2, and excess stimulation of NF-κB, a major regulator of chemokine expression and inflammation. Finally, systemic delivery of thrombin rapidly stimulated lung chemokine expression in vivo These data uncover a novel mechanism whereby loss of serine protease inhibition leads to lung lymphocyte accumulation.-Solleti, S. K., Srisuma, S., Bhattacharya, S., Rangel-Moreno, J., Bijli, K. M., Randall, T. D., Rahman, A., Mariani, T. J. Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation.

Results of directly applied activated carbon cloth in chronic wounds: a preliminary study.

OBJECTIVE: Activated carbon (AC) has been used in wound therapy as an active substance inside dressings. Applying AC directly on a wound is a new concept. The aim of this study was to analyse the outcomes of chronic wounds which were managed with directly applied activated carbon knitted cloth (ACC, Zorflex) in Swiss patients. METHOD: A retrospective analysis of the records of all patients with chronic wounds treated with ACC between 1 October 2013 and 31 December 2015 in an outpatient wound clinic. Chronic was defined as a wound being present for >3 weeks. Malignant wounds were excluded. The main outcome was the time to complete closure or readiness for spilt-thickness skin grafting (STSG). Descriptive data, including nutritional status and angiology results were obtained. RESULTS: There were 36 women and 34 men, median age 68 years old. The median body mass index (BMI) 28.1kg/m2 and 76% (n=53) of patients had comorbidities. Angiology exam results showed signs of reduced arterial perfusion in 13% (n=9) of patients and malnutrition in 11% (n=8). Of the wounds included 34% (n=24) were on the trunk and 66% (n=46) on the extremities. The median wound size was 6.9cm2 (range: 0.1-300cm2). The wounds on the trunk were larger than wounds on extremities (10 versus 2cm2). Overall, median time to wound closure was 51 days. In 94% (n=66) of patients, wounds closed without further intervention and 6% (n=4) underwent STSG. Patients with comorbidities showed longer wound healing times compared with those without. No adverse events such as allergies or skin irritation occurred. Cost analysis, including personnel and material and stratified according known wound closure times, showed ACC (US$ 1252) to be like hydrocolloids (US$ 1128), but substantially lower than white gauze (US$ 3026) and negative pressure wound therapy (NPWT) (US$ 2578). CONCLUSION: ACC applied directly on chronic wounds of different aetiology is safe with short closure times. The cost efficiency is high. It combines the positive features of other wound dressings, such as hydrocolloids and NPWT, without their disadvantages. The dressing change of ACC is easy and non-specialised nurses or even patients themselves can be taught to perform it.

The production and antiprotozoal activity of abietane diterpenes in Salvia austriaca hairy roots grown in shake flasks and bioreactor.

The biomass and concentration of bioactive quinone methide-type diterpenes in hairy roots of Salvia austriaca were determined and compared with levels of these metabolites in roots of field-grown plants. The cultures were maintained in shake flasks and a nutrient sprinkle bioreactor. Diterpene production was more efficient in the shake flask root culture than the bioreactor one. Biomass and diterpene production within the shake flask culture was evaluated using Schenk and Hildebrandt (SH), Gamborg (B5), and woody plant medium (WPM), with both full- and half-strength macro and micronutrient concentrations (1/2 SH, 1/2 B5, and 1/2 WPM). Among the tested media, SH medium proved to be most effective for biomass and diterpene production. In this medium, the transformed roots accumulated the levels of taxodone (3.89 mg g-1 DW; equivalent to 63.3 mg L-1), taxodione (1.15 mg g-1 DW; equivalent to 17.4 mg L-1), 15-deoxy-fuerstione (2.15 mg g-1 DW; equivalent to 32.5 mg L-1), and 7-(2'-oxohexyl)-taxodione (0.076 mg g-1 DW; equivalent to 1.1 mg L-1). Three diterpenes were also detected in the roots of S. austriaca intact plants, but their concentrations were lower than those in hairy root culture. No 7-(2'-oxohexyl)-taxodione was found in the roots of field-grown plants. The hairy roots were able to maintain high metabolite levels even for 6 years of cultivation. Taxodone, taxodione, 15-deoxy-fuerstione, and 7-(2'-oxohexyl)-taxodione were tested for in vitro activity against Trypanosoma brucei rhodesiense, T. cruzi, and Plasmodium falciparum and their cytotoxicity was determined using L6 cells. Among these compounds, taxodione was the most active against T. brucei rhodesiense [IC50 = 0.05 µM with high selectivity, selectivity index (SI) = 38]. Taxodione was found to inhibit the growth of P. falciparum and T. cruzi by 50% at respective concentrations of 1.9 and 7.1 µM (SI values of 1.0 and 0.27). Other diterpenoids demonstrated weaker activity against tested parasites (IC50 values ranging from 0.62 to 194.7 µM) and lower selectivity (SI value ranged from 0.4 to 5.0).

[Secondary plastic and reconstructive measures following deep-dermal burn injuries : Negligent use of bioethanol]. / Sekundär-plastisch-rekonstruktive Maßnahmen nach tiefdermalen Verbrennungsverletzungen : Unsachgemäßer Umgang mit Bioethanol.

One representative case of burns caused by the negligent use of bioethanol, which was treated at our burns centre is used to illustrate the severity and depth of the burn injuries as well as the complexity of the further long-term course of treatment including complex secondary-reconstructive techniques.

Peroxisome Proliferator-Activated Receptor γ and microRNA 98 in Hypoxia-Induced Endothelin-1 Signaling.

Endothelin-1 (ET-1) plays a critical role in endothelial dysfunction and contributes to the pathogenesis of pulmonary hypertension (PH). We hypothesized that peroxisome proliferator-activated receptor γ (PPARγ) stimulates microRNAs that inhibit ET-1 and pulmonary artery endothelial cell (PAEC) proliferation. The objective of this study was to clarify molecular mechanisms by which PPARγ regulates ET-1 expression in vitro and in vivo. In PAECs isolated from patients with pulmonary arterial hypertension, microRNA (miR)-98 expression was reduced, and ET-1 protein levels and proliferation were increased. Similarly, hypoxia reduced miR-98 and increased ET-1 levels and PAEC proliferation in vitro. In vivo, hypoxia reduced miR-98 expression and increased ET-1 and proliferating cell nuclear antigen (PCNA) levels in mouse lung, derangements that were aggravated by treatment with the vascular endothelial growth factor receptor antagonist Sugen5416. Reporter assays confirmed that miR-98 binds directly to the ET-1 3'-untranslated region. Compared with littermate control mice, miR-98 levels were reduced and ET-1 and PCNA expression were increased in lungs from endothelial-targeted PPARγ knockout mice, whereas miR-98 levels were increased and ET-1 and PCNA expression was reduced in lungs from endothelial-targeted PPARγ-overexpression mice. Gain or loss of PPARγ function in PAECs in vitro confirmed that alterations in PPARγ were sufficient to regulate miR-98, ET-1, and PCNA expression. Finally, PPARγ activation with rosiglitazone regimens that attenuated hypoxia-induced PH in vivo and human PAEC proliferation in vitro restored miR-98 levels. The results of this study show that PPARγ regulates miR-98 to modulate ET-1 expression and PAEC proliferation. These results further clarify molecular mechanisms by which PPARγ participates in PH pathogenesis and therapy.

Phospholipase C-ε signaling mediates endothelial cell inflammation and barrier disruption in acute lung injury.

Phospholipase C-ε (PLC-ε) is a unique PLC isoform that can be regulated by multiple signaling inputs from both Ras family GTPases and heterotrimeric G proteins and has primary sites of expression in the heart and lung. Whereas the role of PLC-ε in cardiac function and pathology has been documented, its relevance in acute lung injury (ALI) is unclear. We used PLC-ε(-/-) mice to address the role of PLC-ε in regulating lung vascular inflammation and injury in an aerosolized bacterial LPS inhalation mouse model of ALI. PLC-ε(-/-) mice showed a marked decrease in LPS-induced proinflammatory mediators (ICAM-1, VCAM-1, TNF-α, IL-1ß, IL-6, macrophage inflammatory protein 2, keratinocyte-derived cytokine, monocyte chemoattractant protein 1, and granulocyte-macrophage colony-stimulating factor), lung neutrophil infiltration and microvascular leakage, and loss of VE-cadherin compared with PLC-ε(+/+) mice. These data identify PLC-ε as a critical determinant of proinflammatory and leaky phenotype of the lung. To test the possibility that PLC-ε activity in endothelial cells (EC) could contribute to ALI, we determined its role in EC inflammation and barrier disruption. RNAi knockdown of PLC-ε inhibited NF-κB activity in response to diverse proinflammatory stimuli, thrombin, LPS, TNF-α, and the nonreceptor agonist phorbol 13-myristate 12-acetate (phorbol esters) in EC. Depletion of PLC-ε also inhibited thrombin-induced expression of NF-κB target gene, VCAM-1. Importantly, PLC-ε knockdown also protected against thrombin-induced EC barrier disruption by inhibiting the loss of VE-cadherin at adherens junctions and formation of actin stress fibers. These data identify PLC-ε as a novel regulator of EC inflammation and permeability and show a hitherto unknown role of PLC-ε in the pathogenesis of ALI.

[Children and Adolescents with Asthma Differ in Lung Function Parameters and Exhaled NO from Children and Adolescents with Obesity]. / Kinder und Jugendliche mit Asthma unterscheiden sich in ihrer Lungenfunktion und im exhalierten NO von Kindern und Jugendlichen mit Adipositas.

BACKGROUND: The prevalence of asthma and overweight/obesity in children and adolescents is continuously increasing over the last decades. It remains unclear if overweight/obesity raises the risk of developing asthma or if an uncontrolled asthma increases the risk of developing overweight/obesity by restricting physical activity. OBJECTIVES: We aimed to elucidate, if children and adolescents with overweight/obesity differ from normal-weight asthmatics in lung functions parameters (FEV1, FEV1/VC, MEF50 and SRtot) and in exhaled nitric oxide (FeNO). METHODS: Totally, n=142 children and adolescents aged 6-18 years were included in this study: group 1 comprised n=44 with overweight/obesity defined as a Body-Mass-Index (BMI)>90th percentile; group 2 n=44 with a doctors diagnosed bronchial asthma according to the GINA-guidelines, and group 3 with n=36 pulmonary healthy controls. N=18 children with both asthma and overweight/obesity were excluded from further analysis. We collected data about socio-demographic variables from a standardized questionnaire, bodyplethysmography (FEV1, FEV1/VC, MEF50 and SRtot) and FeNO. RESULTS: Normal-weight children and adolescents with asthma had significantly lower FEV1/VC (Tiffenau-Index 90,9±12,8) and MEF50 (84.0% predicted±27.6) than children with overweight/obesity (97,6±12,4 p=0.001 respectively 99.1±20.9 p=0.001) and healthy controls (98±13,5 p=0,003; 96.7±19.3 p=0.011). Normal weight asthmatics had a significantly higher FeNO (38.3 ppb) than children and adolescents with overweight/obesity (14.0 ppb p=0.014). CONCLUSIONS: Normal-weight children and adolescents with asthma differ significantly both in their lung function parameters as well as in their exhaled nitric oxide concentration from children and adolescents with overweight/obesity. For clinical practice it is important to note that children and adolescents with overweight/obesity have no signs of an obstructive airway diseases and are as resilient as healthy children and adolescents with regard to their lung function. The possible late-onset of asthma symptoms and lung function changes in children and adolescents with overweight/obesity requires further detailed longitudinal studies.

Comprehensive antibiotic susceptibility profiling of Chilean Piscirickettsia salmonis field isolates.

Antibiotics have been extensively used against infections produced by Piscirickettsia salmonis, a fish pathogen and causative agent of piscirickettsiosis and one of the major concerns for the Chilean salmon industry. Therefore, the emergence of resistant phenotypes is to be expected. With the aim of obtaining a landscape of the antimicrobial resistance of P. salmonis in Chile, the susceptibility profiles for quinolones, florfenicol and oxytetracycline (OTC) of 292 field isolates derived from main rearing areas, different hosts and collected over 5 years were assessed. The results allowed for the determination of epidemiological cut-off values that were used to characterize the pathogen population. This work represents the first large-scale field study addressing the antimicrobial susceptibility of P. salmonis, providing evidence of the existence of resistant types with a high incidence of resistance to quinolones. Remarkably, despite the amounts and frequency of therapies, our results disclosed that the issue of resistance to florfenicol and OTC is still in the onset.

Treatment outcome in 60 children with pathological fractures of the humerus caused by juvenile or aneurysmal bone cysts.

The treatment of pathological fractures of the humerus caused by juvenile or aneurysmal bone cysts (JBC/ABC) should be a single approach with a high success rate and low complication rate. This study evaluates how day by day treatment concepts fulfil these aims. Children below 15 years of age with a pathological fracture of the humerus caused by a JBC or ABC between 01.01.2001 and 31.12.2010, were investigated by chart review in four major paediatric trauma centres. Age, gender, fracture localisation, X-ray findings, treatment and outcome - assessed by the Capanna classification (I to IV), were analysed. 60 children [41male, 19 female; mean age: 9 years (4-14 years)] with 43 JBC and 12 ABC were included as well as five cysts, who could not be classified definitively. First treatment was non-operatively in 33 children. Of these 27 cysts did not improve; likewise the supportive installation of cortisone in six patients did not change the outcome. The first treatment consisted of elastic stable intramedullary in 13 children; up to three nail exchanges included. But only six of these reached (nearly) complete resolution (I/II). Overall the combined mechanical and biological treatment with curettage, elastic stable intramedullary nailing, (artificial) bone substitute and in some cases growth factors was performed as the 1st-line treatment in nine patients and further in 2nd or 3rd-line treatments in 13 humeral cysts. More than half of these reached a complete or nearly complete resolution of the cyst (12x I, 5x II, 1x III, 4x IV). Major complications in all operated patients were six nails not removable and two children with upper extremities length differences. Healing rates are low for non-operative treatment, elastic stable intramedullary nailing alone and by using cortisone for cysts resolution in pathological fractures of the humerus. Data support a combined mechanical and biological treatment with curettage, elastic stable intramedullary nailing, (artificial) bone substitute and the use of growth factors.