bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of vaporized nanoemulsions on ultrasound-mediated ablation
Authors: Zhang Peng , Kopechek Jonathan A , Porter Tyrone M
Published: December 2019

Background

The clinical feasibility of using high-intensity focused ultrasound (HIFU) for ablation of solid tumors is limited by the high acoustic pressures and long treatment times required. The presence of microbubbles during sonication can increase the absorption of acoustic energy and accelerate heating. However, formation of microbubbles within the tumor tissue remains a challenge. Phase-shift nanoemulsions (PSNE) have been developed as a means for producing microbubbles within tumors. PSNE are emulsions of submicron-sized, lipid-coated, and liquid perfluorocarbon droplets that can be vaporized into microbubbles using short (<1 ms), high-amplitude (>5 MPa) acoustic pulses. In this study, the impact of vaporized phase-shift nanoemulsions on the time and acoustic power required for HIFU-mediated thermal lesion formation was investigated in vitro.

Methods

PSNE containing dodecafluoropentane were produced with narrow size distributions and mean diameters below 200 nm using a combination of sonication and extrusion. PSNE was dispersed in albumin-containing polyacrylamide gel phantoms for experimental tests. Albumin denatures and becomes opaque at temperatures above 58°C, enabling visual detection of lesions formed from denatured albumin. PSNE were vaporized using a 30-cycle, 3.2-MHz, at an acoustic power of 6.4 W (free-field intensity of 4,586 W/cm2) pulse from a single-element, focused high-power transducer. The vaporization pulse was immediately followed by a 15-s continuous wave, 3.2-MHz signal to induce ultrasound-mediated heating. Control experiments were conducted using an identical procedure without the vaporization pulse. Lesion formation was detected by acquiring video frames during sonication and post-processing the images for analysis. Broadband emissions from inertial cavitation (IC) were passively detected with a focused, 2-MHz transducer. Temperature measurements were acquired using a needle thermocouple.

Results

Bubbles formed at the HIFU focus via PSNE vaporization enhanced HIFU-mediated heating. Broadband emissions detected during HIFU exposure coincided in time with measured accelerated heating, which suggested that IC played an important role in bubble-enhanced heating. In the presence of bubbles, the acoustic power required for the formation of a 9-mm3 lesion was reduced by 72% and the exposure time required for the onset of albumin denaturation was significantly reduced (by 4 s), provided that the PSNE volume fraction in the polyacrylamide gel was at least 0.008%.

Conclusions

The time or acoustic power required for lesion formation in gel phantoms was dramatically reduced by vaporizing PSNE into bubbles. These results suggest that PSNE may improve the efficiency of HIFU-mediated thermal ablation of solid tumors; thus, further investigation is warranted to determine whether bubble-enhanced HIFU may potentially become a viable option for cancer therapy.
Embedding edit distance to enable private keyword search
Authors: Bringer Julien , Chabanne Hervé
Published: December 2019

Background

Our work is focused on fuzzy keyword search over encrypted data in Cloud Computing.

Methods

We adapt results on private identification schemes by Bringeret al. to this new context. We here exploit a classical embedding of the edit distance into the Hamming distance.

Results

Our way of doing enables some flexibility on the tolerated edit distance when looking for close keywords while preserving the confidentiality of the queries.

Conclusion

Our proposal is proved secure in a security model taking into account privacy.
Technical efficiency in the sheep dairy industry: an application on the Sardinian (Italy) sector
Authors: Furesi Roberto , Madau Fabio A , Pulina Pietro
Published: December 2019

Sardinia (Italy) is one of the most important European regions for sheep dairy and sheep milk cheese production. However the Sardinian sheep dairy industry is currently going through a dramatic crisis, and verifying whether it can recover part of its profitability is now a priority. Attention is now focused on estimating whether the sheep dairy firms can improve their productivity by more efficient use of their available technical resources. This paper aims to estimate technical efficiency in the Sardinian sheep dairy industry. A stochastic frontier analysis approach was used on panel data from 36 sheep dairy firms over the period 2004–2009 in order to assess whether there are some margins for technical improvements in productivity, given the existing level of technology. A comparative analysis of private firms and cooperatives was also carried out, in order to establish if there were differences in the technology they used and/or their efficiency in using technical inputs. Our findings suggest that there is technological homogeneity among the firms and between private firms and cooperatives. Technical efficiency is equal to 0.905 and it is significantly different between private firms (0.933) and cooperatives (0.877). Our findings have certain implications for what policies should be implemented in order to improve efficiency in the sector and on the orientation of decision makers strategies.
Magnetic properties of Cr-substituted Co-ferrite nanoparticles synthesized by citrate-gel autocombustion method
Authors: Raghasudha M , Ravinder D , Veerasomaiah P
Published: December 2019

A series of Co-Cr nanoferrites having the chemical formula CoCr
x
Fe2 − x
O4 (x = 0.0, 0.1, 0.3, 0.5, 0.7, 0.9, and 1.0) were synthesized by citrate-gel autocombustion method at a very low temperature (180°C). The X-ray diffraction analysis of as-synthesized powders and sintered powders has confirmed the formation of single-phase cubic spinel structure. The average particle size of the synthesized ferrites was 6 to 12 nm. Magnetic susceptibility measurements using Faraday magnetic susceptibility balance showed the paramagnetic nature of the ferrites. Magnetic properties of Co-Cr nanoferrites were measured using a vibrating sample magnetometer at room temperature in the applied field of 15 kOe. The saturation magnetization decreased from 33.84 to 13.83 emu/g with increase in Cr3+ concentrations, indicating the fact that the lesser magnetic Cr3+ ions substitute Fe3+ ions in the octahedral sublattice of the ferrite. With improvement in the magnetic properties, the synthesized nanoferrites become soft magnetic materials. Such materials are useful in transformer and motor cores to minimize the energy dissipation with the alternating fields associated with AC electrical applications. The coercivity of pure CoFe2O4 was larger than that of the Cr-doped cobalt ferrites.
Effects of hydrogen sulfide on hemodynamics, inflammatory response and oxidative stress during resuscitated hemorrhagic shock in rats
Authors: Ganster Frédérique , Burban Mélanie , de la Bourdonnaye Mathilde , Fizanne Lionel , Douay Olivier , Loufrani Laurent , Mercat Alain , Calès Paul , Radermacher Peter , Henrion Daniel , Asfar Pierre , Meziani Ferhat
Published: December 2019

Introduction

Hydrogen sulfide (H2S) has been shown to improve survival in rodent models of lethal hemorrhage. Conversely, other authors have reported that inhibition of endogenous H2S production improves hemodynamics and reduces organ injury after hemorrhagic shock. Since all of these data originate from unresuscitated models and/or the use of a pre-treatment design, we therefore tested the hypothesis that the H2S donor, sodium hydrosulfide (NaHS), may improve hemodynamics in resuscitated hemorrhagic shock and attenuate oxidative and nitrosative stresses.

Methods

Thirty-two rats were mechanically ventilated and instrumented to measure mean arterial pressure (MAP) and carotid blood flow (CBF). Animals were bled during 60 minutes in order to maintain MAP at 40 ± 2 mm Hg. Ten minutes prior to retransfusion of shed blood, rats randomly received either an intravenous bolus of NaHS (0.2 mg/kg) or vehicle (0.9% NaCl). At the end of the experiment (T = 300 minutes), blood, aorta and heart were harvested for Western blot (inductible Nitric Oxyde Synthase (iNOS), Nuclear factor-κB (NF-κB), phosphorylated Inhibitor κB (P-IκB), Inter-Cellular Adhesion Molecule (I-CAM), Heme oxygenase 1(HO-1), Heme oxygenase 2(HO-2), as well as nuclear respiratory factor 2 (Nrf2)). Nitric oxide (NO) and superoxide anion (O2-) were also measured by electron paramagnetic resonance.

Results

At the end of the experiment, control rats exhibited a decrease in MAP which was attenuated by NaHS (65 ± 32 versus 101 ± 17 mmHg, P < 0.05). CBF was better maintained in NaHS-treated rats (1.9 ± 1.6 versus 4.4 ± 1.9 ml/minute P < 0.05). NaHS significantly limited shock-induced metabolic acidosis. NaHS also prevented iNOS expression and NO production in the heart and aorta while significantly reducing NF-kB, P-IκB and I-CAM in the aorta. Compared to the control group, NaHS significantly increased Nrf2, HO-1 and HO-2 and limited O2- release in both aorta and heart (P < 0.05).

Conclusions

NaHS is protective against the effects of ischemia reperfusion induced by controlled hemorrhage in rats. NaHS also improves hemodynamics in the early resuscitation phase after hemorrhagic shock, most likely as a result of attenuated oxidative stress. The use of NaHS hence appears promising in limiting the consequences of ischemia reperfusion (IR).
International recommendations for glucose control in adult non diabetic critically ill patients
Authors: Ichai Carole , Preiser Jean-Charles ,   for the Société Française d'Anesthésie-Réanimation (SFAR),   Société de Réanimation de langue Française (SRLF) and the Experts group
Published: December 2019

Introduction

The purpose of this research is to provide recommendations for the management of glycemic control in critically ill patients.

Methods

Twenty-one experts issued recommendations related to one of the five pre-defined categories (glucose target, hypoglycemia, carbohydrate intake, monitoring of glycemia, algorithms and protocols), that were scored on a scale to obtain a strong or weak agreement. The GRADE (Grade of Recommendation, Assessment, Development and Evaluation) system was used, with a strong recommendation indicating a clear advantage for an intervention and a weak recommendation indicating that the balance between desirable and undesirable effects of an intervention is not clearly defined.

Results

A glucose target of less than 10 mmol/L is strongly suggested, using intravenous insulin following a standard protocol, when spontaneous food intake is not possible. Definition of the severe hypoglycemia threshold of 2.2 mmol/L is recommended, regardless of the clinical signs. A general, unique amount of glucose (enteral/parenteral) to administer for any patient cannot be suggested. Glucose measurements should be performed on arterial rather than venous or capillary samples, using central lab or blood gas analysers rather than point-of-care glucose readers.

Conclusions

Thirty recommendations were obtained with a strong (21) and a weak (9) agreement. Among them, only 15 were graded with a high level of quality of evidence, underlying the necessity to continue clinical studies in order to improve the risk-to-benefit ratio of glucose control.
Prediction of acid radical ion binding residues by K-nearest neighbors classifier
Authors: Liu Liu , Hu Xiuzhen , Feng Zhenxing , Zhang Xiaojin , Wang Shan , Xu Shuang , Sun Kai
Published: December 2019

Background

Proteins perform their functions by interacting with acid radical ions. Recently, it was a challenging work to precisely predict the binding residues of acid radical ion ligands in the research field of molecular drug design.

Results

In this study, we proposed an improved method to predict the acid radical ion binding residues by using K-nearest Neighbors classifier. Meanwhile, we constructed datasets of four acid radical ion ligand (NO2−, CO32−, SO42−, PO43−) binding residues from BioLip database. Then, based on the optimal window length for each acid radical ion ligand, we refined composition information and position conservative information and extracted them as feature parameters for K-nearest Neighbors classifier. In the results of 5-fold cross-validation, the Matthew’s correlation coefficient was higher than 0.45, the values of accuracy, sensitivity and specificity were all higher than 69.2%, and the false positive rate was lower than 30.8%. Further, we also performed an independent test to test the practicability of the proposed method. In the obtained results, the sensitivity was higher than 40.9%, the values of accuracy and specificity were higher than 84.2%, the Matthew’s correlation coefficient was higher than 0.116, and the false positive rate was lower than 15.4%. Finally, we identified binding residues of the six metal ion ligands. In the predicted results, the values of accuracy, sensitivity and specificity were all higher than 77.6%, the Matthew’s correlation coefficient was higher than 0.6, and the false positive rate was lower than 19.6%.

Conclusions

Taken together, the good results of our prediction method added new insights in the prediction of the binding residues of acid radical ion ligands.
Wheat straw increases the defense response and resistance of watermelon monoculture to Fusarium wilt
Authors: Tang Lili , Nie Shaorui , Li Wenhui , Fan Chao , Wang Siqi , Wu Fengzhi , Pan Kai
Published: December 2019

Background

Wheat straw is a rich resource worldwide. Straw return is an effective strategy to alleviate soil-borne diseases on monoculture watermelon. Previous studies focus on soil structure, physical and chemical properties; however, little is known about the molecular responses on host plant.

Results

No significant difference on the population ofFusarium oxysporumf.sp. niveumrace 1(Fon1) in rhizosphere soil was found between control (no addition of wheat straw) and the treated groups (addition of 1% (T1) or 2% (T2) wheat straw). RNA-Seq analysis showed that 3419 differentially expressed genes were clustered into 8 profiles. KEGG analysis revealed that phenylpropanoid biosynthesis and plant hormone signal transduction were involved in wheat straw induced response in monoculture watermelon. Genes in lignin biosynthesis were found to be upregulated, and the lignin and auxin contents were higher in T1 and T2 compared to the control. Lignin was also enriched and the Fon1 population decreased in watermelon roots treated with wheat straw. The enzyme activities of phenylalanine ammonia-lyase and peroxidase were increased.

Conclusions

Our data suggest that the addition of wheat straw enhances the defense response to Fon1 infection in watermelon through increasing lignin and auxin biosynthesis.
The impact of obstetric interventions and complications on women’s satisfaction with childbirth a population based cohort study including 16,000 women
Authors: Falk Maja , Nelson Marie , Blomberg Marie
Published: December 2019

Background

As a quality marker and a tool for benchmarking between units, a visual analogue scale (VAS) (ranging from 1 to 10) to estimate woman’s satisfaction with childbirth was introduced in 2014. This study aimed to assess how obstetric interventions and complications affected women’s satisfaction with childbirth.

Methods

A retrospective cohort study including 16,775 women with an available VAS score who gave birth between January 2016 and December 2017. VAS score, maternal and obstetric characteristics were obtained from electronic medical records and crude and adjusted odds ratios (aOR) were calculated.

Results

The total prevalence of dissatisfaction with childbirth (VAS 1–3) was 5.7%. The main risk factors for dissatisfaction with childbirth were emergency cesarean section, aOR 3.98 95% confidence interval (CI) 3.27–4.86, postpartum hemorrhage ≥2000 ml, aOR 1.85 95%CI 1.24–2.76 and Apgar score < 7 at five minutes, aOR 2.95 95%CI 1.95–4.47. The amount of postpartum hemorrhage showed a dose-response relation to dissatisfaction with childbirth. Moreover, labor induction, instrumental vaginal delivery, and obstetric anal sphincter injury were significantly associated with women’s dissatisfaction with childbirth. A total number of 4429/21204 (21%) women giving birth during the study period had missing values on VAS. A comparison of characteristics between women with and without a recorded VAS score was performed. There were statistically significant differences in maternal age and maternal BMI between the study population and excluded women due to missing values on VAS. Moreover, 64% of the women excluded were multiparas, compared to 59% in the study population.

Conclusions

Obstetric interventions and complications, including emergency cesareans section and postpartum hemorrhage, were significantly related to dissatisfaction with childbirth.

Such events are common and awareness of these associations might lead to a more individualized care of women during and after childbirth.
Prevalence and determinants of anaemia in pregnant women receiving antenatal care at a tertiary referral hospital in Northern Ghana
Authors: Wemakor Anthony
Published: December 2019

Background

Anaemia during pregnancy is a major public health problem in developing countries. It is important to regularly monitor haemoglobin level in pregnancy and factors associated with it to inform clinical and preventive services. The aim of this study was to assess the prevalence and determinants of anaemia in pregnant women attending antenatal clinic (ANC) of a tertiary referral hospital in Northern Ghana.

Methods

An analytical cross-sectional study involving 400 pregnant women receiving antenatal care in Tamale Teaching Hospital was conducted. Using a semi-structured questionnaire and 24-h dietary recall, data were collected on socio-demographic characteristics, health practices, dietary diversity, anaemia knowledge and haemoglobin level of the women. Anaemia was defined as haemoglobin concentration less than 11 g/dl. Chi-square test and logistic regression analysis were used to identify the independent determinants of pregnancy anaemia.

Results

The mean age and haemoglobin of the women were 28.3 (±4.5) years and 10.81 (±1.41) g/dl respectively. About half of the women 50.8% [95% Confidence Interval (CI): 45.8–55.7] were anaemic and the prevalence of anaemia increased with pregnancy trimester. Among a host of socio-demographic, dietary, and preventive health service factors evaluated, the women’s knowledge on anaemia and pregnancy trimester at interview were the independent determinants of anaemia in pregnancy. Compared to women of the highest anaemia knowledge tertile, women belonging to the lowest (AOR = 2.63, 95% CI: 1.50–4.61) and middle (AOR = 1.92, 95% CI: 1.12–3.27) anaemia knowledge tertiles were about 3 and 2 times more likely to be anaemic respectively. Similarly, women in third trimester of pregnancy were about 4 times more likely to be anaemic compared to those in first trimester at the time of interview (AOR = 3.57, 95% CI: 1.91–6.67).

Conclusions

There is a high prevalence of anaemia, which increases with pregnancy trimester, in pregnant women attending ANC in a tertiary referral hospital in Northern Ghana. The women’s knowledge on anaemia and pregnancy trimester at the time of interview are associated with their anaemia status. The high prevalence of anaemia in pregnancy needs urgent intervention to prevent the occurrence of adverse maternal and neonatal outcomes. Education on anaemia should be intensified at ANCs.
Effects of psychosocial work factors on number of pain sites: The role of sleep quality as mediator
Authors: Vleeshouwers J. , Knardahl S. , Christensen J. O.
Published: December 2019

Background

Objective of the current study was to determine which of thirteen specific psychosocial work factors were related to number of musculoskeletal pain sites (NPS) prospectively over a two-year time span. Furthermore, the study aimed to explore possible mediation of these prospective relationships through sleep problems.

Methods

The study was a two-wave full panel study. Participants included 6277 employees of Norwegian companies, representing a wide range of occupations. Structural equation modelling was employed to analyze direct and indirect effects of thirteen specific psychological- and social work factors on sleep problems and NPS.

Results

Out of the thirteen work factors studied, positive challenges at work, role conflict, decision control, superior support, coworker support, empowering leadership, and social climate were statistically significantly related to subsequent NPS, both directly and indirectly through sleep quality. Sleep quality was related to NPS in all analyses. Most psychosocial work factors exhibited direct effects on either sleep or number of pain sites. Decision demands and control over work pacing were not statistically significantly related to sleep or pain.

Conclusion

In conclusion, the results suggested sleep quality to be involved in the mechanisms by which work affects the number of pain complaints employees experience.

Significance

Findings from this study suggest sleep may play a role in the complex mechanism from work stressors to musculoskeletal pain. Workplace interventions aiming to reduce musculoskeletal pain may wish to target work factors described in this study, as they affect sleep and may thereby increase number of musculoskeletal pain sites.
Safety and tolerability of experimental hookworm infection in humans with metabolic disease: study protocol for a phase 1b randomised controlled clinical trial
Authors: Pierce Doris , Merone Lea , Lewis Chris , Rahman Tony , Croese John , Loukas Alex , McDonald Malcolm , Giacomin Paul , McDermott Robyn
Published: December 2019

Background

Abdominal obesity and presence of the metabolic syndrome (MetS) significantly increase the risk of developing diseases such as Type 2 diabetes mellitus (T2DM) with escalating emergence of MetS and T2DM constituting a significant public health crisis worldwide. Lower prevalence of inflammatory and metabolic diseases such as T2DM in countries with higher incidences of helminth infections suggested a potential role for these parasites in the prevention and management of certain diseases. Recent studies confirmed the potential protective nature of helminth infection against MetS and T2DM via immunomodulation or, potentially, alteration of the intestinal microbiota. This Phase 1b safety and tolerability trial aims to assess the effect of inoculation with helminths on physical and metabolic parameters, immune responses, and the microbiome in otherwise healthy women and men.

Methods

Participants eligible for inclusion are adults aged 18–50 with central obesity and a minimum of one additional feature of MetS recruited from the local community with a recruitment target of 54. In a randomised, double-blind, placebo-controlled design, three groups will receive either 20 or 40 stage three larvae of the human hookworm Necator americanus or a placebo. Eligible participants will provide blood and faecal samples at their baseline and 6-monthly assessment visits for a total of 24 months with an optional extension to 36 months. During each scheduled visit, participants will also undergo a full physical examination and complete diet (PREDIMED), physical activity, and patient health (PHQ-9) questionnaires. Outcome measurements include tolerability and safety of infection with Necator americanus, changes in metabolic and immunological parameters, and changes in the composition of the faecal microbiome.

Discussion

Rising cost of healthcare associated with obesity-induced metabolic diseases urgently calls for new approaches in disease prevention. Findings from this trial will provide valuable information regarding the potential mechanisms by which hookworms, potentially via alterations in the microbiota, may positively influence metabolic health.

Trial registration

The protocol was registered on ANZCTR.org.au on 05 June 2017 with identifier ACTRN12617000818336.

Alternatively, a Google search using the above trial registration number will yield a direct link to the trial protocol within the ANZCTR website.
Lingguizhugan decoction attenuates doxorubicin-induced heart failure in rats by improving TT-SR microstructural remodeling
Authors: Li Xueping , Xu Guangmin , Wei Shujun , Zhang Baocheng , Yao Huan , Chen Yuchi , Liu Weiwei , Wang Baojia , Zhao Juan , Gao Yongxiang
Published: December 2019

Background

Lingguizhugan decoction (LGZG), an ancient Chinese herbal formula, has been used to treat cardiovascular diseases in eastern Asia. We investigated whether LGZG has protective activity and the mechanism underlying its effect in an animal model of heart failure (HF).

Methods

A rat model of HF was established by administering eight intraperitoneal injections of doxorubicin (DOX) (cumulative dose of 16 mg/kg) over a 4-week period. Subsequently, LGZG at 5, 10, and 15 mL/kg/d was administered to the rats intragastrically once daily for 4 weeks. The body weight, heart weight index (HWI), heart weight/tibia length ratio (HW/TL), and serum BNP level were investigated to assess the effect of LGZG on HF. Echocardiography was performed to investigate cardiac function, and H&E staining to visualize myocardial morphology. Myocardial ultrastructure and T-tubule-sarcoplasmic reticulum (TT-SR) junctions were observed by transmission electron microscopy. The JP-2 protein level was determined by Western blotting. The mRNA level of CACNA1S and RyR2 and the microRNA-24 (miR-24) level were assayed by quantitative RT-PCR.

Results

Four weeks after DOX treatment, rats developed cardiac damage and exhibited a significantly increased BNP level compared with the control rats (169.6 ± 29.6 pg/mL versus 80.1 ± 9.8 pg/mL, P < 0.001). Conversely, LGZG, especially at the highest dose, markedly reduced the BNP level (93.8 ± 17.9 pg/mL, P < 0.001). Rats treated with DOX developed cardiac dysfunction, characterized by a strong decrease in left ventricular ejection fraction compared with the control (58.5 ± 8.7% versus 88.7 ± 4.0%; P < 0.001). Digoxin and LGZG improved cardiac dysfunction (79.6 ± 6.1%, 69.2 ± 2.5%, respectively) and preserved the left ventricular ejection fraction (77.9 ± 5.1, and 80.5 ± 4.9, respectively, P < 0.01). LGZG also improved the LVEDD, LVESD, and FS and eliminated ventricular hypertrophy, as indicated by decreased HWI and HW/TL ratio. LGZG attenuated morphological abnormalities and mitochondrial damage in the myocardium. In addition, a high dose of LGZG significantly downregulated the expression of miR-24 compared with that in DOX-treated rats (fold change 1.4 versus 3.4, P < 0.001), but upregulated the expression of JP-2 and antagonized DOX-induced T-tubule TT-SR microstructural remodeling. These activities improved periodic Ca2+ transients and cell contraction, which may underly the beneficial effect of LGZG on HF.

Conclusions

LGZG exerted beneficial effects on DOX-induced HF in rats, which were mediated in part by improved TT-SR microstructural remodeling.
Antibiotic resistance in porcine pathogenic bacteria and relation to antibiotic usage
Authors: Holmer I. , Salomonsen C. M. , Jorsal S. E. , Astrup L. B. , Jensen V. F. , Høg B. Borck , Pedersen K.
Published: December 2019

Background

Optimal treatment and prudent use of antimicrobials for pigs is imperative to secure animal health and prevent development of critical resistance. An important step in this one-health context is to monitor resistance patterns of important animal pathogens. The aim of this study was to investigate the antimicrobial resistance patterns of five major pathogens in Danish pigs during a period from 2004 to 2017 and elucidate any developments or associations between resistance and usage of antibiotics.

Results

The minimum inhibitory concentration (MIC) forEscherichia coli, Actinobacillus pleuropneumoniae, Streptococcus suis, Bordetella bronchiseptica,andStaphylococcus hyicuswas determined to representatives of antibiotic classes relevant for treatment or surveillance.Escherichia coliisolates were mostly sensitive to fluoroquinolones and colistin, whereas high levels of resistance were observed to ampicillin, spectinomycin, streptomycin, sulfonamides and tetracycline. While resistance levels to most compounds remained relatively stable during the period, resistance to florfenicol increased from 2.1% in 2004 to 18.1% in 2017, likely in response to a concurrent increase in usage. A temporal association between resistance and usage was also observed for neomycin.E. coliserovars O138 and O149 were generally more resistant than O139. ForA. pleuropneumoniae, the resistance pattern was homogenous and predictable throughout the study period, displaying high MIC values only to erythromycin whereas almost all isolates were susceptible to all other compounds. MostS. suisisolates were sensitive to penicillin whereas high resistance levels to erythromycin and tetracycline were recorded, and resistance to erythromycin and trimethoprim increasing over time. ForS. hyicus,sensitivity to the majority of the antimicrobials tested was observed. However, penicillin resistance was recorded in 69.4–88.9% of the isolates. AllB. bronchisepticaisolates were resistant to ampicillin, whereas all but two isolates were sensitive to florfenicol. The data obtained have served as background for a recent formulation of evidence-based treatment guidelines for pigs.

Conclusions

Antibiotic resistance varied for some pathogens over time and in response to usage. Resistance to critically important compounds was low. The results emphasize the need for continuous surveillance of resistance patterns also in pig pathogenic bacteria.
Urban Moveability and physical activity in children: longitudinal results from the IDEFICS and I.Family cohort
Authors:   on behalf of the IDEFICS and the I.Family consortia, Buck Christoph , Eiben Gabriele , Lauria Fabio , Konstabel Kenn , Page Angie , Ahrens Wolfgang , Pigeot Iris
Published: December 2019

Background

Physical activity (PA) is one of the major protective behaviours to prevent non-communicable diseases. Positive effects of the built environment on PA are well investigated, although evidence of this association is mostly based on cross-sectional studies. The present study aims to investigate the longitudinal effects of built environment characteristics in terms of a moveability index on PA of children in their transition phase to adolescence using data of the IDEFICS/I.Family cohort.

Methods

We used data on 3394 accelerometer measurements of 2488 children and adolescents aged 3 to 15 years old from survey centres of three countries, Germany, Italy, and Sweden, who participated in up to three surveys over 6 years. In network-dependent home neighbourhoods, a moveability index was calculated based on residential density, land use mix, street connectivity, availability of public transport and public open spaces such as green spaces and public playgrounds in order to quantify opportunities for PA of children and adolescents. Linear trajectories of light PA (LPA) and moderate-to-vigorous PA (MVPA) were estimated using linear mixed models accounting for repeated measurements nested within individuals. Least squares means were estimated to quantify differences in trajectories over age.

Results

LPA and MVPA declined annually with age by approximately 20 min/day and 2 min/day respectively. In girls, the moveability index showed a consistent significantly positive effect on MVPA ($$ \hat{\beta} $$β̂ = 2.14, 95% CI: (0.11; 4.16)) for all ages, while in boys the index significantly lessened the decline in LPA with age for each year. ($$ \hat{\beta} $$β̂ = 2.68, 95% CI: (0.46; 4.90)).

Availability of public open spaces was more relevant for MVPA in girls and LPA in boys during childhood, whereas in adolescence, residential density and intersection density became more important.

Conclusion

Built environment characteristics are important determinants of PA and were found to have a supportive effect that ameliorates the decline in PA during the transition phase from childhood to adolescence. In childhood environmental support for leisure time PA through public open spaces was found to be the most protective factor whereas in adolescence the positive influence of street connectivity and residential density was most supportive of physical activity.
Ontogeny of the facial phenotypic variability in Mexican patients with 22q11.2 deletion syndrome
Authors: Farrera Arodi , Villanueva María , Vizcaíno Alfredo , Medina-Bravo Patricia , Balderrábano-Saucedo Norma , Rives Mariana , Cruz David , Hernández-Carbajal Elizabeth , Granados-Riveron Javier , Sánchez-Urbina Rocío
Published: December 2019

Background

22q11.2 deletion syndrome is a medical condition that results from genomic loss at chromosome 22. Affected patients exhibit large variability that ranges from a severe condition to mild symptoms. In addition, the spectrum of clinical features differs among populations and even within family members. The facial features related to this syndrome are not an exception, and although part of its variation arises through development, few studies address this topic in order to understand the intra and inter-population heterogeneities. Here, we analyze the ontogenetic dynamics of facial morphology of Mexican patients with del22q11.2 syndrome.

Methods

Frontal facial photographs of 37 patients (mean age = 7.65 ± 4.21 SE) with del22q11.2DS and 200 control subjects (mean age = 7.69 ± 4.26 SE) were analyzed using geometric morphometric methods. Overall mean shape and size differences between patients and controls were analyzed, as well as differences in ontogenetic trajectories (i.e. development, growth, and allometry).

Results

We found that Mexican patients show typical traits that have been reported for the Caucasian population. Additionally, there were significant differences between groups in the facial shape and size when all the ontogenetic stages were considered together and, along ontogeny. The developmental and allometric trajectories of patients and controls were similar, but they differed in allometric scaling. Finally, patients and controls showed different growth trajectories.

Conclusion

The results suggest that the typical face of patients with del22q11.2DS is established prenatally; nonetheless, the postnatal ontogeny could influence the dysmorphology and its variability through size-related changes.
Harnessing the power of theorising in implementation science
Authors: Kislov Roman , Pope Catherine , Martin Graham P. , Wilson Paul M.
Published: December 2019

Theories occupy different positions in the scientific circle of enquiry as they vary in scope, abstraction, and complexity. Mid-range theories play a crucial bridging role between raw empirical observations and all-encompassing grand-theoretical schemes. A shift of perspective from ‘theories’ as products to ‘theorising’ as a process can enable empirical researchers to capitalise on the two-way relationships between empirical data and different levels of theory and contribute to the advancement of knowledge. This can be facilitated by embracing theoretically informative (in addition to merely theoretically informed) research, developing mechanism-based explanations, and broadening the repertoire of grand-theoretical orientations.
PI3K/Akt inhibitor partly decreases TNF-α-induced activation of fibroblast-like synoviocytes in osteoarthritis
Authors: Liu Songyang , Cao Chenxi , Zhang Yujun , Liu Guangyu , Ren Weixia , Ye Yanqi , Sun Tiezheng
Published: December 2019

Background

The Cadherin-11 and PI3K/Akt pathway are increasingly recognized as the potential therapeutic target of osteoarthritis (OA) synovitis. The study aimed to investigate the role of PI3K/Akt signaling pathway in the expression of Cadherin-11 and migration and invasive capacity of fibroblast-like synoviocytes (FLS) of OA patients under stimulation of TNF-α and to explore the effect of the PI3K/Akt inhibitor and Cadherin-11 antibody in the therapy of the collagenase-induced osteoarthritis (CIOA) mice.

Methods

FLS were primarily cultured from synovium of osteoarthritic patients during total knee arthroplasty. Under the simulation of TNF-α, with or without PI3K/Akt inhibitor LY294002, Cadherin-11 expression was detected by real-time PCR and Western blot, as well as the migration and invasive capacity changes of OA FLS. Cadherin-11 antibody was injected intraarticularly or LY294002 was injected intraperitoneally in CIOA mice to evaluate the changes of synovitis score, cartilage damage, and Cadherin-11 expression.

Results

TNF-α stimulation increased Cadherin-11 expression at mRNA and protein level in OA FLS and also increased the phosphorylation-dependent activation of Akt. PI3K inhibitor LY294002 attenuated TNF-α-induced overexpression of Cadherin-11 and decreased the invasive capacity of OA FLS. Intraperitoneal injection of PI3K inhibitor LY294002 could decrease the Cadherin-11 protein expression in synovium of CIOA mice, although it has no significant inhibitory effect on synovitis and cartilage damage. Intraarticular injection of Cadherin-11 antibody attenuated the synovitis and cartilage damage in the CIOA joints and decreased Cadherin-11 expression in the synovial lining.

Conclusions

PI3K/Akt pathway was associated with TNF-α-induced activation of OA FLS, which may involve in the pathogenesis of osteoarthritis. Anti-Cadherin-11 therapy in CIOA mice could attenuate the pathological changes of OA joints.
Risk analysis and clinical outcomes of intraoperative periprosthetic fractures: a retrospective study of 481 bipolar hemiarthroplasties
Authors: Bellova Petri , Baecker Hinnerk , Lotzien Sebastian , Brandt Marvin , Schildhauer Thomas A. , Gessmann Jan
Published: December 2019

Background

Intraoperative periprosthetic fractures (IPF) are a well-described complication following hip hemiarthroplasty. Our aims were to identify risk factors that characterize IPF and to investigate postoperative mobility.

Methods

We retrospectively reviewed 481 bipolar hemiarthroplasties for displaced femoral neck fractures; of which, 421 (87.5%) were performed without cement, from January 2013 to March 2018. Data on the patients’ demographics, comorbidities, femoral canal geometry (Dorr canal type, Canal Flare Index), surgeon’s experience (junior vs. senior surgeon), and timing of surgery (daytime vs. on-call duty) were obtained. In patients with intraoperative fractures, further information was obtained. Patient mobility was assessed using matched-pair analysis. Mobility was classified according to the NHFD mobility score. The chi-square test, Fisher’s exact test, and Fisher-Freeman-Halton exact test were used for comparison between categorical variables, while the Mann-WhitneyUtest was used for continuous variables. The data analysis was performed using SPSS.

Results

Of 481 procedures, 34 (7.1%) IPFs were encountered. The Dorr canal type C was identified as a significant risk factor (p= .004). Other risk factors included female sex (OR 2.30, 95% CI .872–6.079), stovepipe femur (OR 1.749, 95% CI .823–3.713), junior surgeon (OR 1.204, 95% CI .596–2.432), and on-call-duty surgery (OR 1.471, 95% CI .711–3.046), although none showed a significant difference. Of 34 IPFs, 25 (73.5%) were classified as Vancouver type A. The treatment of choice was cerclage wiring. Within the 12 matched pairs identified, the postoperative mobility was slightly worse for the IPF group (delta = .41).

Conclusions

IPF is a serious complication with bipolar hemiarthroplasty. The identification of risk factors preoperatively, in particular femur shape, is crucial and should be incorporated into the decision-making process.
Predicting outcome in patients with moderate to severe traumatic brain injury using electroencephalography
Authors: Haveman Marjolein E. , Van Putten Michel J. A. M. , Hom Harold W. , Eertman-Meyer Carin J. , Beishuizen Albertus , Tjepkema-Cloostermans Marleen C.
Published: December 2019

Background

Better outcome prediction could assist in reliable quantification and classification of traumatic brain injury (TBI) severity to support clinical decision-making. We developed a multifactorial model combining quantitative electroencephalography (qEEG) measurements and clinically relevant parameters as proof of concept for outcome prediction of patients with moderate to severe TBI.

Methods

Continuous EEG measurements were performed during the first 7 days of ICU admission. Patient outcome at 12 months was dichotomized based on the Extended Glasgow Outcome Score (GOSE) as poor (GOSE 1–2) or good (GOSE 3–8). Twenty-three qEEG features were extracted. Prediction models were created using a Random Forest classifier based on qEEG features, age, and mean arterial blood pressure (MAP) at 24, 48, 72, and 96 h after TBI and combinations of two time intervals. After optimization of the models, we added parameters from the International Mission for Prognosis And Clinical Trial Design (IMPACT) predictor, existing of clinical, CT, and laboratory parameters at admission. Furthermore, we compared our best models to the online IMPACT predictor.

Results

Fifty-seven patients with moderate to severe TBI were included and divided into a training set (n = 38) and a validation set (n = 19). Our best model included eight qEEG parameters and MAP at 72 and 96 h after TBI, age, and nine other IMPACT parameters. This model had high predictive ability for poor outcome on both the training set using leave-one-out (area under the receiver operating characteristic curve (AUC) = 0.94, specificity 100%, sensitivity 75%) and validation set (AUC = 0.81, specificity 75%, sensitivity 100%). The IMPACT predictor independently predicted both groups with an AUC of 0.74 (specificity 81%, sensitivity 65%) and 0.84 (sensitivity 88%, specificity 73%), respectively.

Conclusions

Our study shows the potential of multifactorial Random Forest models using qEEG parameters to predict outcome in patients with moderate to severe TBI.
Human leucocyte antigen class I in hormone receptor-positive, HER2-negative breast cancer: association with response and survival after neoadjuvant chemotherapy
Authors: Sinn Bruno Valentin , Weber Karsten E. , Schmitt Wolfgang Daniel , Fasching Peter A. , Symmans William Fraser , Blohmer Jens-Uwe , Karn Thomas , Taube Eliane Tabea , Klauschen Frederick , Marmé Frederik , Schem Christian , Stickeler Elmar , Ataseven Beyhan , Huober Jens , von Minckwitz Gunter , Seliger Barbara , Denkert Carsten , Loibl Sibylle
Published: December 2019

Background

Clinical application of cancer immunotherapy requires a better understanding of tumor immunogenicity and the tumor microenvironment. HLA class I molecules present antigens to CD8+ cytotoxic cells. Their loss or downregulation is frequently found in tumors resulting in reduced T cell responses and worse prognosis.

Methods

We evaluated HLA class I heavy chain expression by immunohistochemistry in 863 biopsies (GeparTrio trial). Patients received neoadjuvant chemotherapy and adjuvant endocrine treatment if tumors were hormone receptor-positive (HR+). In parallel, the expression of HLA-A was analyzed using a microarray cohort of 320 breast cancer patients from the MD Anderson Cancer Center. We evaluated its association with clinical outcome, tumor-infiltrating lymphocytes (TILs), and immune cell metagenes.

Results

In HR+/HER2− breast cancer, HLA class I heavy chain expression was associated with increased TILs and better response to chemotherapy (7% vs. 14% pCR rate, P = 0.029), but worse disease-free survival (hazard ratio (HR) 1.6 (1.1–2.4); P = 0.024). The effect was significant in a multivariate model adjusted for clinical and pathological variables (HR 1.7 (1.1–2.6); P = 0.016) and was confirmed by analysis of HLA-A in a microarray cohort. HLA-A was correlated to most immune cell metagenes. There was no association with response or survival in triple-negative or HER2+ disease.

Conclusions

The study confirms the negative prognostic role of lymphocytes in HR+ breast cancer and points at a complex interaction between chemotherapy, endocrine treatment, and tumor immunogenicity. The results point at a subtype-specific and potentially treatment-specific role of tumor-immunological processes in breast cancer with different implications in triple-negative and hormone receptor-positive disease.
Characterization of organoid cultured human breast cancer
Authors: Goldhammer Nadine , Kim Jiyoung , Timmermans-Wielenga Vera , Petersen Ole William
Published: December 2019

Organoid cultures are increasingly used to model human cancers experimentally with a view to tailoring personalized medicine and predicting drug responses. Breast cancer is no exception, but in particular, primary breast cancer poses some inherent difficulties due to the frequent presence of residual non-malignant cells in the biopsies. We originally developed an assay for the distinction between malignant and non-malignant structures in primary breast cancer organoid cultures (Petersen et al., Proc Natl Acad Sci (USA) 89(19):9064–8, 1992). Here, we apply this assay to assess the frequency of normal-like organoids in primary breast carcinoma cultures and the cellular composition as a consequence of passaging. We find that in consecutively collected samples of primary human breast cancers, residual non-malignant tissues were observed histologically in five out of ten biopsies. Based on relevant morphogenesis and correct polarization as recorded by expression in luminal epithelial cells of mucin 1 (Muc1), occludin, and keratin 19 (K19) and expression in basal cells of integrin β4, p63, and K14, non-malignant organoids were present in all primary human breast cancer-derived cultures. Furthermore, passaging in a contemporary culture medium was in favor of the selective expansion of basal-like cells. We conclude that organoid cultures of human breast cancers are most representative of the tissue origin in primary culture.
Acupoint transcutaneous electrical nerve stimulation in hospitalized COPD patients with severe dyspnoea: study protocol for a randomized controlled trial
Authors: Fernández-Jané Carles , Vilaró Jordi
Published: December 2019

Background

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a major cause of hospital admissions and dyspnoea is its main symptom. Some studies have concluded that a new modality of acupuncture, called acupoint transcutaneous electrical nerve stimulation (acuTENS), could reduce dyspnoea in patients with COPD by increasing β-endorphin levels. However, those trials have been conducted mainly on patients in stable condition. This study aims to determine whether the administration of acuTENS can reduce dyspnoea in patients hospitalized for AECOPD.

Methods

A multicentre randomized control trial with blinding of participants and assessors will be conducted. A sample of 60 patients will be randomly assigned to receive 45 min of either real acuTENS or sham acuTENS treatment once a day for five consecutive days. The trial will be conducted at the “Hospital del Mar” in Barcelona (Spain) and the “Hospital Sant Joan de Déu de Manresa” in Manresa (Spain). The Borg scale at baseline and days 1 to 5 will be the primary outcome. Secondary outcomes will be the duration of the hospitalization, quantity of drugs administrated, expiratory peak flow adverse effects and mortality and readmissions at 3 months.

Discussion

AcuTENS is a non-pharmacological, non-invasive and inexpensive intervention. This trial will help to elucidate the potential role of acuTENS in the treatment of AECOPD.

Trial registration

ClinicalTrials.gov identifier: NCT02998957. Recruitment status: Recruiting. First posted: 21 December 2016. Last update posted: 2 October 2018. Trial registration dataset is available in Additional file 1. Protocol version 03. Issue date: 20 March 2018. Author: Carles Fernández.