Deterioration of lung function during the first week of COVID-19 has been observed when patients remain with insufficient respiratory support. Patient self-inflicted lung injury (P-SILI) is theorized as the responsible, but there is not robust experimental and clinical data to support it. Given the limited understanding of P-SILI, we describe the physiological basis of P-SILI and we show experimental data to comprehend the role of regional strain and heterogeneity in lung injury due to increased work of breathing.In addition, we discuss the current approach to respiratory support for COVID-19 under this point of view.

Although tuberculosis accounts for the highest mortality from a bacterial infection on a global scale, questions persist regarding its origin. One hypothesis based on modern Mycobacterium tuberculosis complex (MTBC) genomes suggests their most recent common ancestor followed human migrations out of Africa approximately 70,000 years before present. However, studies using ancient genomes as calibration points have yielded much younger dates of less than 6000 years. Here, we aim to address this discrepancy through the analysis of the highest-coverage and highest-quality ancient MTBC genome available to date, reconstructed from a calcified lung nodule of Bishop Peder Winstrup of Lund (b. 1605-d. 1679).

A metagenomic approach for taxonomic classification of whole DNA content permitted the identification of abundant DNA belonging to the human host and the MTBC, with few non-TB bacterial taxa comprising the background. Genomic enrichment enabled the reconstruction of a 141-fold coverage M. tuberculosis genome. Iolithic emergence for the MTBC.

The three-dimensional organization of the genome in the nucleus plays an integral role in many biological processes, including gene expression. The genome is folded into DNA loops that bring together distal regulatory elements and genes. Cohesin, a ring-shaped protein complex, is a major player in the formation of DNA loops. Cohesin is composed of a core trimer and one of two variant STAG subunits, STAG1 or STAG2. It is not understood whether variant STAG proteins give rise to cohesin complexes with distinct functions. Recent studies have begun to characterize the roles of STAG1 and STAG2, with partially contradictory results.

Here, we generate stable single-knockout embryonic stem cell lines to investigate the individual contributions of STAG1 and STAG2 in regulating cohesin chromosomal localization and function. We report both overlapping roles for STAG1 and STAG2 in cohesin localization and somewhat distinct roles in gene expression. STAG1 and STAG2 occupy the same sites across the genome, yet do not ees in gene expression. The roles of STAG1 and STAG2 in mouse embryonic stem cells may be somewhat different than in other cell types, due to their relative expression levels. These results advance our understanding of the link between mammalian genome organization and gene expression during development and disease contexts.Noncoding RNAs (ncRNAs) are a large segment of the transcriptome that do not have apparent protein-coding roles, but they have been verified to play important roles in diverse biological processes, including disease pathogenesis. With the development of innovative technologies, an increasing number of novel ncRNAs have been uncovered; information about their prominent tissue-specific expression patterns, various interaction networks, and subcellular locations will undoubtedly enhance our understanding of their potential functions. Here, we summarized the principles and innovative methods for identifications of novel ncRNAs that have potential functional roles in cancer biology. Moreover, this review also provides alternative ncRNA databases based on high-throughput sequencing or experimental validation, and it briefly describes the current strategy for the clinical translation of cancer-associated ncRNAs to be used in diagnosis.

National and provincial funding was invested to increase the quantity and quality of patient-oriented research (POR) across Canada. Capacity development became a priority to ensure all stakeholders were prepared to engage in POR. In part, this need was met through an annual Studentship competition in the province of Alberta, providing funding to students whose research incorporated principles of POR. However, despite efforts to build capacity in the health research trainee population, little is known about the outcomes of these programmes. This evaluation study examined the outcomes of a POR capacity development programme for health research trainees.

Final impact narrative reports were submitted by the 21 Studentship programme awardees for 2015 and 2016 who represent a variety of health disciplines across three major research universities. The reports describe the programme outcomes as well as the overall impact on individual, project and professional development as POR trainees. A synthesis of structured for more robust competencies for POR. Further exploration of evaluation methods for short-term awards and sustainability of capacity development programmes is warranted.

The public-private mix of healthcare remains controversial. This paper examines physicians’ preferences for public sector work in the context of dual practice, whilst accounting for other differences in the characteristics of jobs.

A discrete choice experiment is conducted with data from 3422 non-GP specialists from the Medicine in Australia Balancing Employment and Life (MABEL) panel survey of physicians.

Physicians prefer to work in the public sector, though the value of working in the public sector is very small at 0.14% of their annual earnings to work an additional hour per week. These preferences are heterogeneous. Contrary to other studies that show risk averse individuals prefer public sector work, for physicians, we find that those averse to taking career or clinical risks prefer to work in the private sector. Those with relatively low earnings prefer public sector work and those with high earnings prefer private sector work, though these effects are small.

Other job characteristics are more important than the sector of work, suggesting that these should be the focus of policy to influence specialist’s allocation of time between sectors.

Other job characteristics are more important than the sector of work, suggesting that these should be the focus of policy to influence specialist’s allocation of time between sectors.

Microglial dysfunction is implicated in frontotemporal lobar degeneration (FTLD). Although studies have reported excessive microglial activation or senescence (dystrophy) in Alzheimer’s disease (AD), few have explored this in FTLD. We examined regional patterns of microglial burden, activation and dystrophy in sporadic and genetic FTLD, sporadic AD and controls.

Immunohistochemistry was performed in frontal and temporal grey and white matter from 50 pathologically confirmed FTLD cases (31 sporadic, 19 genetic 20 FTLD-tau, 26 FTLD-TDP, four FTLD-FUS), five AD cases and five controls, using markers to detect phagocytic (CD68-positive) and antigen-presenting (CR3/43-positive) microglia, and microglia in general (Iba1-positive). Microglial burden and activation (morphology) were assessed quantitatively for each microglial phenotype. Iba1-positive microglia were assessed semi-quantitatively for dystrophy severity and qualitatively for rod-shaped and hypertrophic morphology. Microglia were compared in each regi disease mechanisms. This supports investigation of microglial dysfunction in disease models and consideration of anti-senescence therapies in clinical trials.

This study demonstrates regionally variable microglial involvement in FTLD and links this to underlying disease mechanisms. This supports investigation of microglial dysfunction in disease models and consideration of anti-senescence therapies in clinical trials.

This study investigated the role of fibrinogen-like protein 1 (FGL1) in regulating gefitinib resistance of PC9/GR non-small cell lung cancer (NSCLC).

The effect of different concentrations of gefitinib on cell proliferation were evaluated using the CCK-8 assay. FGL1 expression in the normal human bronchial epithelial cell line Beas-2B, as well as four lung tumor cell lines, H1975, A549, PC9, and PC9/GR, was investigated by using western blotting and qRT-PCR. FGL1 was knocked down using small interfering RNA to evaluate the effects of FGL1 on PC9 and PC9/GR. The correlation between FGL1 expression and gefitinib resistance was determined in vitro via CCK-8 and colony formation assays, and flow cytometry and in vivo via flow cytometry and immunohistochemistry.

FGL1 expression was significantly upregulated in non-small cell lung cancer cells with EGFR mutation and higher in the gefitinib-resistant NSCLC cell line PC9/GR than in the gefitinib-sensitive NSCLC cell line PC9. Further, FGL1 expression in PC9 andnib.

Respirable crystalline silica causes lung carcinomas and many thousand future cancer cases are expected in e.g. Europe. Critical questions are how silica causes genotoxicity in the respiratory epithelium and if new cases can be avoided by lowered permissible exposure levels. In this study we investigate early DNA damaging effects of low doses of silica particles in respiratory epithelial cells in vitro and in vivo in an effort to understand low-dose carcinogenic effects of silica particles.

We find DNA damage accumulation already after 5-10 min exposure to low doses (5 μg/cm

) of silica particles (Min-U-Sil 5) in vitro. DNA damage was documented as increased levels of γH2AX, pCHK2, by Comet assay, AIM2 induction, and by increased DNA repair (non-homologous end joining) signaling. The DNA damage response (DDR) was not related to increased ROS levels, but to a NLRP3-dependent mitochondrial depolarization. Particles in contact with the plasma membrane elicited a Ser198 phosphorylation of NLRP3, co-localization of NLRP3 to mitochondria and depolarization. FCCP, a mitochondrial uncoupler, as well as overexpressed NLRP3 mimicked the silica-induced depolarization and the DNA damage response. A single inhalation of 25 μg silica particles gave a similar rapid DDR in mouse lung. Biomarkers (CC10 and GPRC5A) indicated an involvement of respiratory epithelial cells.

Our findings demonstrate a novel mode of action (MOA) for silica-induced DNA damage and mutagenic double strand breaks in airway epithelial cells. This MOA seems independent of particle uptake and of an involvement of macrophages. Our study might help defining models for estimating exposure levels without DNA damaging effects.

Our findings demonstrate a novel mode of action (MOA) for silica-induced DNA damage and mutagenic double strand breaks in airway epithelial cells. This MOA seems independent of particle uptake and of an involvement of macrophages. Our study might help defining models for estimating exposure levels without DNA damaging effects.

Body weight support systems with three or more degrees of freedom (3-DoF) are permissive and safe environments that provide unloading and allow unrestricted movement in any direction. This enables training of walking and balance control at an early stage in rehabilitation. Transparent systems generate a support force vector that is near vertical at all positions in the workspace to onlyminimally interfere with natural movement patterns. Patients with impaired balance, however, may benefit from additional mediolateral support that can be adjusted according to their capacity. An elegant solution for providing balance support might be by rendering viscous damping along the mediolateral axis via the software controller. Before use with patients, we evaluated if control-rendered mediolateral damping evokes the desired stability enhancement in able-bodied individuals.

A transparent, cable-driven robotic body weight support system (FLOAT) was used to provide transparent body weight support with and without medioal damping could enable therapists to select combinations of unloading and stability specifically for each patient and to adapt this in a task specific manner. This could extend the impact of transparent 3-DoF body weight support systems, enabling training of gait and active balance from an early timepoint onwards in the rehabilitation process for a wide range of mobility activities of daily life.

Adding mediolateral damping to 3-DoF body weight support systems is an effective method of increasing frontal plane stability during walking in able-bodied participants. Building on these results, adjustable mediolateral damping could enable therapists to select combinations of unloading and stability specifically for each patient and to adapt this in a task specific manner. This could extend the impact of transparent 3-DoF body weight support systems, enabling training of gait and active balance from an early time point onwards in the rehabilitation process for a wide range of mobility activities of daily life.

We hypothesized that preoperative pelvic morphology may affect postoperative anterior coverage and postoperative clinical range of motion (ROM) leading to postoperative pincer type femoroacetabular impingement (FAI). The aim of this study was to evaluate the relationships between preoperative bone morphology and postoperative ROMs to prevent postoperative FAI after periacetabular osteotomy.

Sixty-eight patients (71 hips) with hip dysplasia participated in this study and underwent curved PAO. The acetabular fragment was usually moved only by lateral rotation of the acetabulum, without intraoperative anterior or posterior rotation. The pre- and postoperative three-dimensional center-edge (CE) angles were measured and compared to the postoperative ROM.

Preoperative medial anterior CE angle was significantly associated with postoperative anterior CE angle, and the correlation coefficient of medial anterior CE and postoperative anterior CE was higher than the coefficient of preoperative anterior CE and posto. Further, the combination with preoperative medial anterior acetabular coverage and femoral anteversion can predict postoperative internal rotation at 90° flexion. Therefore, the direction of acetabular reorientation should be carefully considered when the patients have high preoperative medial anterior CE angle and small femoral anteversion.

Electrospun (e-spun) nanofibers for wound dressing have attracted wide attention due to its large specific surface area, large porosity and breathability. Compared with solution electrospinning (e-spinning), melt e-spinning is more bio-friendly without toxic solvent participation, which provides the possibility of in situ e-spinning on wounds directly. However, previously reported melt e-spinning devices were usually bulky and cumbersome due to their necessary heating unit, and different components were separated to avoid electrostatic interference.

In this article, we report on a self-powered hand-held melt e-spinning gun which can work without any external power supply (outdoors). The problem of electrostatic interference for this integrated device was solved by using a special high heat transfer insulation unit. The apparatus is easy and safe to operate by a single hand due to its small volume (24 × 6 × 13cm

) and light weight (about 450g). Some biodegradable polymers, for example, polycaprolactone (PCL) fibers were successful e-spun onto wounds directly by using this dressing gun.

PCL fibrous membrane has good biocompatibility and can be in situ electrospun to wound surface as a wound dressing by the portable melt e-spinning gun. Besides wound dressing, this hand-held melt e-spinning gun may be used in 3D printing and experimental teaching demonstration aids.

PCL fibrous membrane has good biocompatibility and can be in situ electrospun to wound surface as a wound dressing by the portable melt e-spinning gun. Besides wound dressing, this hand-held melt e-spinning gun may be used in 3D printing and experimental teaching demonstration aids.

Thioesters of coenzyme A participate in 5% of all enzymatic reactions. In microbial cell factories, they function as building blocks for products of recognized commercial value, including natural products such as polyketides, polyunsaturated fatty acids, biofuels, and biopolymers. A core spectrum of approximately 5-10 short chain thioesters is present in many microbes, as inferred from their genomic repertoire. The relevance ofthese metabolites explains the high interest to trace and quantify them in microbial cells.

Here, we describe a common workflow for extraction and absolute quantification of short chain CoA thioesters in different gram-positive and gram-negative bacteria and eukaryotic yeast, i.e. Corynebacterium glutamicum, Streptomyces albus, Pseudomonas putida, and Yarrowia lipolytica. The approach assessed intracellularCoA thioesters down to the picomolar leveland exhibited high precision and reproducibility for all microbes, as shown by principal component analysis. Furthermore, it provided int range, the developed approach appears useful to be applied this purpose. Hereby, the possibility to use one single protocol promises to facilitate automatized efforts, which rely on standardized workflows.

The high relevance of short chain CoA thioesters to synthetize industrial products and the interesting insights gained from the examples shown in this work, suggest analyzing these metabolites in microbial cell factories more routinely than done so far. Due to its broad application range, the developed approach appears useful to be applied this purpose. Hereby, the possibility to use one single protocol promises to facilitate automatized efforts, which rely on standardized workflows.

Does Glyceryl trinitrate (GTN) administered during rewarming on cardiopulmonary bypass (CPB) impact time to completion of rewarming prior to separation from CPB circuit, early post-op patient peripheral – core temperature gradient, time to maintenance of normothermia (core temperature > 36.5 °C) for minimum of 2 h in the initial post-op period, and plasma lactate concentrations initially post-CPB.

Single centre prospective randomized trial conducted in the Mater Misericordiae University teaching hospital in Dublin Ireland.

ISRCTN registry, ISRCTN10480871 , registered 16th of August 2017. 82 patients enrolled. Patients randomised to low dose GTN infusion (0.01 mcg/kg/min) or higher dose GTN infusion (0.5 mcg/kg/min) during rewarming on CPB.

There was no significant difference between the treatment arms for the total time to being rewarmed, U = 759.0, p = 0.84. There were also no differences between the treatment arms for the time to achieve core temperature greater than 36.5 after two hours, U = 714.0, p = 0.52, the time to achieve plateau core skin temperature, U = 688.0, p = 0.37, and the post-intervention protamine lactate, U = 721.0, p = 0.56.

Higher dose GTN infusion during rewarming on CPB does not improve peripheral-core temperature gradient post operatively and has no effect on post-operative lactate concentrations.

Higher dose GTN infusion during rewarming on CPB does not improve peripheral-core temperature gradient post operatively and has no effect on post-operative lactate concentrations.

Recent studies have reported that neutrophil-to-lymphocyte ratio (NLR) is associated with cardiovascular disease. The aim of the present study was to investigate the prognostic value of NLR in aortic disease.

We systematically searched electronic databases (Cochrane, PubMed, Elsevier, Medline, and Embase) from their inception to March 2020. Observational studies that evaluated the relationship between NLR and aortic disease were eligible for critical appraisal. Data were extracted from applicable articles, risk ratio (RR), weighted mean differences (MD) and 95% confidence intervals (CI) were calculated by RevMan 5.3, and statistical heterogeneity was assessed by the I

statistic.

Fourteen studies enrolling 4066 individuals were included in the meta-analysis. Compared with the control group, NLR was significantly higher in the aortic disease group (MD 3.44, 95%CI 0.81-6.07, P = 0.01, I

 = 99%). The NLR was also significantly higher in non-survivors with aortic disease, compared to the survivors (MD 4.62, 95%CI 2.75-6.50, P < 0.00001, I

 = 60%). Compared with the aortic disease patients with a low NLR, mortality was significantly higher in those with a high NLR (RR 2.63, 95%CI 1.79-3.86, P < 0.00001, I

 = 67%).

Based on current evidence, an elevated NLR was associated with aortic disease and in-hospital mortality. Raised NLR also demonstrated a significantly increased the risk of mortality after surgical repair in aortic disease patients. NLR may be a good prognostic biomarker in aortic disease and deserve further research in this area.

Based on current evidence, an elevated NLR was associated with aortic disease and in-hospital mortality. Raised NLR also demonstrated a significantly increased the risk of mortality after surgical repair in aortic disease patients. NLR may be a good prognostic biomarker in aortic disease and deserve further research in this area.

Child mortality rates during hospitalisation for acute illness and after discharge are unacceptably high in many under-resourced settings. Childhood vulnerability to recurrent illness, and death, is linked to their families’ situations and ability to make choices and act (their agency). We examined vulnerability and agency across treatment-seeking journeys for acutely ill children and considered the implications for policy and practice.

A qualitative sub-study was embedded within the prospective CHAIN Network cohort study, which is investigating mechanisms of inpatient and post-hospital discharge mortality among acutely ill young children across a spectrum of nutritional status. Primary data were collected from household members of 20 purposively selected cohort children over 18 months through formal interviews (total n = 74), complemented by informal discussions and observations. Data were analysed using narrative and thematic approaches.

Treatment-seeking pathways were often long and complex, particulis essential. Promising interventions need to be co-designed with community representatives and health providers and carefully tested for unintended negative consequences and potential for sustainable scale-up.

To support children’s care and recovery, health systems must be more responsive to the needs of families facing multiple and interacting vulnerabilities. Reducing incurred treatment costs, improving interpersonal quality of care, and strengthening continuity of care across facilities is essential. Promising interventions need to be co-designed with community representatives and health providers and carefully tested for unintended negative consequences and potential for sustainable scale-up.

HIV-1 Vpr encodes a 14kDa protein that has been implicated in viral pathogenesis through modulation of several host cell functions. In addition to pro-apoptotic and cytostatic properties, Vpr can redirect cellular E3 ubiquitin ligases (such as DCAF1-Cul4A E3 ligase complex) to target many host proteins and interfere with their functions. Among them, Vpr binds the uracil DNA glycosylase UNG2, which controls genome uracilation, and induces its specific degradation leading to loss of uracil removal activity in infected cells. Considering the essential role of UNG2 in antibody diversification in B-cells, we evaluated the impact of Vpr on UNG2 fate in B lymphocytes and examined the functional consequences of UNG2 modulations on class switch recombination (CSR).

The impact of Vpr-induced UNG2 deregulation on CSR proficiency was evaluated by using virus-like particles able to deliver Vpr protein to target cells including the murine model CSR B cell line CH12F3 and mouse primary B-cells. Co-culture experiments weo study alterations of the B-cell response by using Vpr as a specific CSR blocking tool. Moreover, our results raise the question of whether extracellular HIV-1 Vpr detected in some patients may manipulate the antibody diversification process that engineers an adapted response against pathogenic intruders and thereby contribute to the intrinsic B-cell humoral defect reported in infected patients.A method with high sensitivity, good accuracy and fast response is of ever increasing importance for the simultaneous detection of AA, DA and UA. In this paper, a simple and sensitive electrochemical sensor, which based on the polyvinylpyrrolidone (PVP)-graphene composite film modified glassy carbon electrode (PVP-GR/GCE), was presented for detecting ascorbic acid (AA), dopamine (DA) and uric acid (UA) simultaneously. The PVP-GR/GCE has excellent electrocatalytic activity for the oxidation of AA, DA and UA. The second-order derivative linear sweep voltammetry was used for the electrochemical measurements. The peak potential differences of DA-AA, DA-UA, and UA-AA (measured on the PVP-GR/GCE) were 212, 130 and 342 mV respectively. Besides, the over potential of AA, DA and UA reduced obviously, so did the peak current increase. Under the optimum conditions, the linear ranges of AA, DA and UA were 4.0 μM-1.0 mM, 0.02-100 μM, and 0.04-100 μM, respectively. The detection limits were 0.8 μM, 0.002 μM and 0.02 μM for AA, DA, and UA. The electrochemical sensor presented the advantages of high sensitivity and selectivity, excellent reproducibility and long-term stability. Furthermore, the sensor was successfully applied to the analysis of real samples.

Spasticity after lesions of central motor pathways may be disabling and there is a need for new, cost-effective treatment methods. One novel approach is offered by the electro-dress Mollii®, primarily designed to enhance reciprocal inhibition of spastic muscles by multifocal, transcutaneous antagonist stimulation.

The Mollii® suit was set individually for 20 participants living with spasticity and hemiplegia after stroke and used in the home setting for 6 weeks. Usability and perceived effects were monitored by weekly telephone interviews. Outcome was assessed by use of the NeuroFlexor™ method for quantification of the neural component (NC) of resistance to passive stretch (spasticity), and the modified Ashworth scale (MAS) for total resistance, Fugl-Meyer Assessment of motor recovery for sensorimotor function in upper (FM-UE) and lower extremities (FM-LE), activity performance with the Action Research Arm Test (ARAT), Berg balance scale, 10 m and 6 min walk tests, and perceived functioning with the Strokolled study combined with rehabilitation interventions to enhance effects on activity and participation domains.

NCT04076878 . Registered 2 September 2019 – Retrospectively registered.

NCT04076878 . Registered 2 September 2019 – Retrospectively registered.

Extracellular vesicles (EVs) have been broadly studied in malaria for nearly a decade. These vesicles carry various functional biomolecules including RNA families such as microRNAs (miRNA). These EVs-derived microRNAs have numerous roles in host-parasite interactions and are considered promising biomarkers for disease severity. However, this field lacks clinical studies of malaria-infected samples. In this study, EV specific miRNAs were isolated from the plasma of patients from Thailand infected with Plasmodium vivax and Plasmodium falciparum. In addition, it is postulated that these miRNAs were differentially expressed in these groups of patients and had a role in disease onset through the regulation of specific target genes.

EVs were purified from the plasma of Thai P. vivax-infected patients (n = 19), P. falciparum-infected patients (n = 18) and uninfected individuals (n = 20). EV-derived miRNAs were then prepared and abundance of hsa-miR-15b-5p, hsa-miR-16-5p, hsa-let-7a-5p and hsa-miR-150-5p was asse50-5p and hsa-miR-15b-5p was observed in P. vivax-infected patients while hsa-let-7a-5p was up-regulated in both P. vivax-infected and P. falciparum-infected patients. These findings will require further validation in larger cohort groups of malaria patients to fully understand the contribution of these EVs miRNAs to malaria detection and biology.

An upregulation of hsa-miR-150-5p and hsa-miR-15b-5p was observed in P. vivax-infected patients while hsa-let-7a-5p was up-regulated in both P. vivax-infected and P. falciparum-infected patients. These findings will require further validation in larger cohort groups of malaria patients to fully understand the contribution of these EVs miRNAs to malaria detection and biology.

Recurrent and relapsing arthritis has been proposed to describe a group of arthritis with recurring and periodic nature, in which the joints are intermittently involved. This study reports three non-FMF patients with heterozygous MEFV gene mutations and an extraordinary arthritis as a recurrent synovitis of hip (RSH).

During 16-years from 2003 to 2019 at pediatric rheumatologic clinic among 195 recorded files with chronic oligoarthritis, 3 patients with diagnosis of recurrent synovitis of hip (RSH) were reviewed thoroughly. Peripheral blood was collected from patients and the samples were screened for the 12 common MEFV gene pathogenic variants.

This study included three patients, two female and one male with relapsing idiopathic arthritis that has been located on hip joints as a sole manifestation and pathologic findings of MEFV mutations as follow A744S, V726A, and R761H.

On the basis of possible role of MEFV gene in different rheumatic disease, MEFV gene related arthritis may be considered as a background of RSH particularly in Mediterranean area.

On the basis of possible role of MEFV gene in different rheumatic disease, MEFV gene related arthritis may be considered as a background of RSH particularly in Mediterranean area.

The ability of adipose tissue-derived multipotent mesenchymal stromal cells/mesenchymal stem cells (ASCs) to differentiate in neural lineages promises progress in the field of regenerative medicine, especially for replacing neuronal tissue damaged by different neurological disorders. Reprogramming of ASCs can be induced by the growth medium with neurogenic inductors and specific growth factors. We investigated the neural differentiation potential of canine ASCs using several growth media (KEM, NIMa, NIMb, NIMc) containing various combinations of neurogenic inductors B27 supplement, valproic acid, forskolin, N2-supplement, and retinoic acid. Cells were first preconditioned in the pre-differentiation neural induction medium (mitogenically stimulated; STIM1), followed by the induction of neuronal differentiation.

After 3, 6, and 9 days of neural induction, elongated neural-like cells with bipolar elongations were observed, and some oval cells with light nuclei appeared. The expression of neuronal markers tub for the regenerative therapy of nerve damage and could be useful in the future for therapy or the modelling of neurodegenerative diseases.

The differentiation repertoire of canine ASCs extends beyond mesodermal lineages. Using a defined neural induction medium, the canine ASCs differentiated into neural lineages and expressed markers of neuronal and glial cells, and also displayed the typical neuronal morphology. Differentiated ASCs can thus be a source of neural cellular lineages for the regenerative therapy of nerve damage and could be useful in the future for therapy or the modelling of neurodegenerative diseases.

This is the first report about a vaginal leiomyoma concomitant with an ovarian luteoma in a bitch.

A 11-year-old intact female Labrador retriever was referred because of anuria, constipation and protrusion of a vaginal mass through the vulvar commissure. The bitch had high serum progesterone concentration (4.94 ng/ml). Because of the possibility of progesterone responsiveness causing further increase of the vaginal mass and since the bitch was a poor surgical candidate a 10 mg/kg aglepristone treatment was started SC on referral day 1. A computerized tomography showed a 12.7 × 6.5 × 8.3 cm mass causing urethral and rectal compression, ureteral dilation and hydronephrosis. A vaginal leiomyoma was diagnosed on histology. As serum progesterone concentration kept increasing despite aglepristone treatment, a 0.02 ng/mL twice daily IM alfaprostol treatment was started on day 18. As neither treatment showed remission of clinical signs or luteolysis, ovariohysterectomy was performed on referral day 35. Multiple corpora lutea were found on both ovaries. On histology a luteoma was diagnosed on the left ovary. P4 levels were undetectable7 days after surgery. Recovery was uneventful and 12 weeks after surgery tomography showed a reduction of 86.7% of the vaginal mass. The bitch has been in good health and able to urinate without any complication ever since.

This case demonstrates the importance of identifying progesterone related conditions as well as the importance of judiciously using a combined medical and surgical approach.

This case demonstrates the importance of identifying progesterone related conditions as well as the importance of judiciously using a combined medical and surgical approach.

In Lactobacillus plantarum, fructooligosaccharides (FOS) metabolism is controlled by both global and local regulatory mechanisms. Although catabolite control protein A has been identified as a global regulator of FOS metabolism, the functions of local regulators remain unclear. This study aimed to elucidate the roles of two local regulators, SacR1 and SacR2, in the regulation of FOS metabolism in L. plantarum both in vitro and in vivo.

The inactivation of sacR1 and sacR2 affected the growth and production of metabolites for strains grown on FOS or glucose, respectively. A reverse transcription-quantitative PCR analysis of one wild-type and two mutant strains (ΔsacR1 and ΔsacR2) of L. plantarum identified SacR1 and SacR2 as repressors of genes relevant to FOS metabolism in the absence of FOS, and these genes could be induced or derepressed by the addition of FOS. The analysis predicted four potential transcription factor binding sites (TFBSs) in the putative promoter regions of two FOS-related clusters. The binding of SacR1 and SacR2 to these TFBSs both in vitro and in vivo was verified using electrophoretic mobility shift assays and chromatin immunoprecipitation, respectively. A consensus sequence of WNNNNNAACGNNTTNNNNNW was deduced for the TFBSs of SacR1 and SacR2.

Our results identified SacR1 and SacR2 as local repressors for FOS metabolism in L. plantarum. The regulation is achieved by the binding of SacR1 and SacR2 to TFBSs in the promoter regions of FOS-related clusters. The results provide new insights into the complex network regulating oligosaccharide metabolism by lactic acid bacteria.

Our results identified SacR1 and SacR2 as local repressors for FOS metabolism in L. plantarum. The regulation is achieved by the binding of SacR1 and SacR2 to TFBSs in the promoter regions of FOS-related clusters. The results provide new insights into the complex network regulating oligosaccharide metabolism by lactic acid bacteria.

Whey is a major pollutant generated by the dairy industry. To decrease environmental pollution caused by the industrial release of whey, new prospects for its utilization need to be urgently explored. Here, we investigated the possibility of using whey powder to produce 2,3-butanediol (BDO), an important platform chemical.

Klebsiella oxytoca strain PDL-0 was selected because of its ability to efficiently produce BDO from lactose, the major fermentable sugar in whey. After deleting genes pox, pta, frdA, ldhD, and pflB responding for the production of by-products acetate, succinate, lactate, and formate, a recombinant strain K. oxytoca PDL-K5 was constructed. Fed-batch fermentation using K. oxytoca PDL-K5 produced 74.9g/L BDO with a productivity of 2.27g/L/h and a yield of 0.43g/g from lactose. In addition, when whey powder was used as the substrate, 65.5g/L BDO was produced within 24h with a productivity of 2.73g/L/h and a yield of 0.44g/g.

This study demonstrated the efficiency of K. oxytoca PDL-0 for BDO production from whey. Due to its non-pathogenicity and efficient lactose utilization, K. oxytoca PDL-0 might also be used in the production of other important chemicals using whey as the substrate.

This study demonstrated the efficiency of K. oxytoca PDL-0 for BDO production from whey. Due to its non-pathogenicity and efficient lactose utilization, K. oxytoca PDL-0 might also be used in the production of other important chemicals using whey as the substrate.

Comprehensive primary care practices, through preconception, preventive, curative, and rehabilitative care, have been a global priority in the promotion of health. However, the scope of primary care services has still been in decline in China. Studies on the factors for primary care service scope have centred on human resources and infrastructure; the role of direct government subsidies (DGS) on services scope of primary care facilities were left unanswered. This study aimed to explore the association between the DGS and services scope of primary care facilities in China.

A multi-stage, clustered cross-sectional survey using self-administrated questionnaire was conducted among primary care facilities of 36 districts/counties in China. A total of 770 primary care facilities were surveyed with 757 (98.3%) valid respondents. Of the 757 primary care facilities, 469 (62.0%) provided us detailed information of financial revenue and DGS from 2009 to 2016. Therefore, 469 primary care facilities from 31 counties/dof primary care and distorted incentive structure of primary care. Future improvements of DGS should focus on the incentive of broader basic medical services provision, such as clarifying service scope of primary care facilities and strategic procurement with a performance-based subsidies system to determine resource allocation.

While the DGS successfully achieved equalization of basic preventive and public health services, the disproportionate proportion of DGS to financial revenue is associated with narrowed service scope, which might cause underutilization of primary care and distorted incentive structure of primary care. Future improvements of DGS should focus on the incentive of broader basic medical services provision, such as clarifying service scope of primary care facilities and strategic procurement with a performance-based subsidies system to determine resource allocation.

Few studies have examined relationships between physical activity (PA) during mid-age and health costs in women. The aim of this study was to investigate associations between PA levels and trajectories over 12 years with medical and pharmaceutical costs in mid-age Australian women.

Data from 6953 participants in the Australian Longitudinal Study on Women’s Health (born in 1946-1951) were analysed in 2019. PA was self-reported in 2001 (50-55y), 2007 (56-61y) and 2013 (62-67y). PA data were linked with 2013-2015 data from the Medicare (MBS) and Pharmaceutical (PBS) Benefits Schemes. Quantile regression was used to examine associations between PA patterns [always active, increasers, decreasers, fluctuaters or always inactive (reference)] with these medical and pharmaceutical costs.

Among women who were consistently inactive (< 500 MET.minutes/week) in 2001, 2007 and 2013, median MBS and PBS costs (2013 to 2015) were AUD4261 and AUD1850, respectively. Those costs were AUD1728 (95%CI 443-3013) and AUD578 (95%CI 426-729) lower among women who were consistently active in 2001, 2007 and 2013 than among those who were always inactive. PBS costs were also lower in women who were active at only one survey (AUD205; 95%CI 49-360), and in those whose PA increased between 2001 and 2013 (AUD388; 95%CI 232-545).

Maintaining 'active’ PA status was associated with 40% lower MBS and 30% lower PBS costs over three years in Australian women. Helping women to remain active in mid-life could result in considerable savings for both women and the Australian government.

Maintaining 'active’ PA status was associated with 40% lower MBS and 30% lower PBS costs over three years in Australian women. Helping women to remain active in mid-life could result in considerable savings for both women and the Australian government.

Experimental designs using surrogate gait-like movements, such as in functional magnetic resonance imaging (MRI), cannot fully capture the cortical activation associated with overground gait. Overground gait in a robotic exoskeleton may be an ideal tool to generate controlled sensorimotor stimulation of gait conditions like 'active’ (i.e. user moves with the device) and 'passive’ (i.e. user is moved by the device) gait. To truly understand these neural mechanisms, functional near-infrared spectroscopy (fNIRS) would yield greater ecological validity. Thus, the aim of this experiment was to use fNIRS to delineate brain activation differences between 'Active’ and 'Passive’ overground gait in a robotic exoskeleton.

Fourteen healthy adults performed 10 walking trials in a robotic exoskeleton for Passive and Active conditions, with fNIRS over bilateral frontal and parietal lobes, and electromyography (EMG) over bilateral thigh muscles. Digitization of optode locations and individual T1 MRI scans were used to den with individuals unable to walk independently.

The parietal cortex is active during passive robotic exoskeleton gait, a novel finding as research to date has not recorded posterior to the primary somatosensory cortex. Increased activation of the parietal cortex may be related to the planning of limb coordination while maintaining postural control. Future neurorehabilitation research could use fNIRS to examine whether exoskeletal gait training can increase gait-related brain activation with individuals unable to walk independently.

After the collapse of the Soviet Union at the beginning of the 1990s, people who inject drugs spiked in Eastern Europe. Facing local repression and an array of factors encouraging emigration, some users have migrated to France. This population now make up to a third of the patient list of some harm reduction services in Paris. This article aims to present original data on the sociodemographic profiles of these users, on their migration trajectory, their life conditions, and on the evolution of their drug use practices since arriving in Paris.

Data were collected as part of the ANRS-Coquelicot Survey, an HIV and HCV seroprevalence study among French-speaking people who use drugs. A sub-sample of Russian-speaking drug users who had relocated from Eastern Europe to live in Paris completed a quantitative questionnaire (N = 150) and a qualitative semi-structured interview (N = 20). The survey aimed to describe participants’ backgrounds, and a thematic analysis of interviews was conducted to explore participantrofiles and behaviors of the study population lead us to make two recommendations to offer stronger global care to these users in Paris and to reform drug policy in their home countries by integrating it into a public health approach.

Porcine circovirus type 3 is the most recently discovered porcine circovirus, and an emerging pathogen. In this study the status of its presence on some Slovenian farms is reported. The effectiveness of the vaccine against porcine circovirus type 2 was assessed against porcine circovirus type 3. Group samples of oral fluid, faeces and individual serum samples were taken from six different pig categories and tested for presence of viral DNA, using both real time and conventional PCR. Positive samples were subjected to direct Sanger sequencing. Nucleotide sequences were analyzed and compared to GenBank PCV3 sequences.

Positive samples were sent for genome sequencing, which confirmed the presence of virus in all different pig categories on five farms. A high to moderate correlation of strong statistical significance was found between individual serum samples, oral fluid and faeces. Slovenian PCV3 was found to be distributed in a way similar to that of other countries. Slovenian PCV3 nt sequences are highly related, sharing more than 99.5% nt identity. On one farm a commercially available vaccine against porcine circovirus type 2 was used on 3-week-old pigs. It did not affect the presence of porcine circovirus type 3 in oral fluid or sera of any of the seven age groups of pigs, each with two control groups.

The results constitute the first discovery of the virus in Slovenia. Genome sequencing has revealed a high degree of similarity between Slovenian and GenBank isolates.

The results constitute the first discovery of the virus in Slovenia. Genome sequencing has revealed a high degree of similarity between Slovenian and GenBank isolates.Arthropod-borne viruses or arbovirus, are most commonly associated with acute infections, resulting on various symptoms ranging from mild fever to more severe disorders such as hemorrhagic fever. Moreover, some arboviral infections can be associated with important neuroinflammation that can trigger neurological disorders including encephalitis, paralysis, ophthalmological impairments, or developmental defects, which in some cases, can lead to long-term defects of the central nervous system (CNS). This is well illustrated in Zika virus-associated congenital brain malformations but also in West Nile virus-induced synaptic dysfunctions that can last well beyond infection and lead to cognitive deficits. Here, we summarize clinical and mechanistic data reporting on cognitive disturbances triggered by arboviral infections, which may highlight growing public health issues spanning the five continents.

Self-rated health is an useful indicator of the general health in specific populations and used to propose interventions after service in the military context. However, there is scarce literature about self- rated health (SRH) in the Canadian Veterans of the Reserve Force and its relationship with demographic, health and occupational characteristics of this specific group. The aims of this research were to determine the SRH in Canadian Reserve Force Veterans and to explore the relationship between demographic, military service and health factors by reserve class.

Data from the individuals was collected from the Life After Service (LASS) 2013 survey, including Veterans with Reserve Class C (n = 922) and Class A/B (n = 476). Bivariate and multivariate analysis using logistic regression models, were used to assess the association between the demographic characteristics, physical health, mental health, and military service characteristics and the self-rate health by both reserve classes.

The overall prevale = 9.8, CI 3.70-25.75) were associated with higher odds of poor SRH.

These results suggested that the relationship of poor SRH with demographic, health and military occupation domains varied depending on the class on the Reserve Force Service. Different strengths of association showed different risk compositions for both populations. This can be used to better understand the health and well-being of Veterans of the Reserve Force.

These results suggested that the relationship of poor SRH with demographic, health and military occupation domains varied depending on the class on the Reserve Force Service. Different strengths of association showed different risk compositions for both populations. This can be used to better understand the health and well-being of Veterans of the Reserve Force.

Culicoides hypersensitivity (CH) is induced in horses by salivary allergens of Culicoides midges. In Iceland, the causal Culicoides species for CH are not present. Previous epidemiological data indicated that Icelandic horses are more susceptible to CH when they are exported from Iceland and first exposed to Culicoides at adult age. Horses born in countries where Culicoides is endemic, develop the disease less frequently. Here, we established a longitudinal allergy model to identify predictive and diagnostic serological biomarkers of CH.

Sixteen adult Icelandic horses from Iceland were imported to the Northeastern United States (US) during the winter and were kept in the same environment with natural Culicoides exposure for the next two years. None of the horses showed clinical allergy during the first summer of Culicoides exposure. In the second summer, 9/16 horses (56%) developed CH. Allergen specific IgE and IgG isotype responses in serum samples were analysed using nine potential Culicoides allergens redictive biomarker of CH in horses that have been exposed to Culicoides but did not yet develop clinical signs.

Our results identified IgG5 and IgG3/5 antibodies against Cul o 2 and Cul o 3, respectively, as markers for CH during and shortly after the allergy season in the Northeastern US. In addition, Cul o 2 specific IgG3/5 antibodies may be valuable as a predictive biomarker of CH in horses that have been exposed to Culicoides but did not yet develop clinical signs.

Surface staining and deeper discoloration characteristics of peroxide-based bleaching agents in the nicotine stain in dental enamel model were evaluated in the present study.

Nicotine stained dental enamel fragments (n = 36) were prepared and were subjected to the bleaching ingredients for a fixed treatment time of 30 min. The bleaching agents were composed of limonene, coconut diethanolamide, and carbamide peroxide served as solvent, nonionic surfactant, and oxidizer, respectively. Optical analysis was carried out considering color stability via colorimeter and UV-Vis spectrometer.

Degrees of color variations were significantly influenced by nicotine content and bleaching ingredient factors. They varied in the range of approximately 3.00 and 5.00 units for all tooth-bleaching agents. The most prominent degrees of color variation elevations were obtained in the tooth bleaching formulae set #2 (1.0% limonene + 20% coconut diethanolamide) in the stained tooth model in comparison to set #1 (0.5% limonene + 10% coconut diethanolamide) and set #3 (1.5% limonene + 30% coconut diethanolamide), partly due to the perceptible color changes. The lowest degree of color variation under a dose limitation was found in the tooth bleaching formulae set #2 + 10% carbamide peroxide formulation. Absorbance spectra were also evaluated after the interaction of bleaching treatment. They confirmed a relationship between nicotine content and discoloration characteristics of the tooth bleaching formulae set #2 + 10% carbamide peroxide.

Carbamide peroxide is considered as generator of free radicals. It converts the color of stains to clear by oxidizing the organic compounds in the stained dental enamel model, achieving whiteness enhancement.

Carbamide peroxide is considered as generator of free radicals. It converts the color of stains to clear by oxidizing the organic compounds in the stained dental enamel model, achieving whiteness enhancement.