Fusarium wilt is currently spreading in banana growing regions around the world leading to substantial losses. The disease is caused by the fungus Fusarium oxysporum f. sp. cubense (Foc), which is further classified into distinct races according to the banana varieties that they infect. Cavendish banana is resistant to Foc race 1, to which the popular Gros Michel subgroup succumbed last century. Cavendish effectively saved the banana industry, and became the most cultivated commercial subgroup worldwide. However, Foc tropical race 4 (TR4) subsequently emerged in Southeast Asia, causing significant yield losses due to its high level of aggressiveness to cultivars of Cavendish, and other commonly grown cultivars. Preventing further spread is crucially important in the absence of effective control methods or resistant market-acceptable banana cultivars. Implementation of quarantine and containment measures depends on early detection of the pathogen through reliable diagnostics. In this study, we tested the hypothesis that secreted in xylem (SIX) genes, which currently comprise the only known family of effectors in F. oxysporum, contain polymorphisms to allow the design of molecular diagnostic assays that distinguish races and relevant VCGs of Foc. We present specific and reproducible diagnostic assays based on conventional PCR targeting SIX genes, using as templates DNA extracted from pure Foc cultures. Sets of primers specifically amplify regions of: SIX6 in Foc race 1, SIX1 gene in TR4, SIX8 in subtropical race 4, SIX9/SIX10 in Foc VCG 0121, and SIX13 in Foc VCG 0122. These assays include simplex and duplex PCRs, with additional restriction digestion steps applied to amplification products of genes SIX1 and SIX13. Assay validations were conducted to a high international standard including the use of 250 Fusarium spp. isolates representing 16 distinct Fusarium species, 59 isolates of F. oxysporum, and 21 different vegetative compatibility groups (VCGs). Tested parameters included inter and intraspecific analytical specificity, sensitivity, robustness, repeatability, and reproducibility. The resulting suite of assays is able to reliably and accurately detect R1, STR4, and TR4 as well as two VCGs (0121 and 0122) causing Fusarium wilt in bananas.

Palmitoleic acid (16:1Δ9) is one kind of ω-7 fatty acids (ω-7 FAs) widely used in food, nutraceutical and industry. However, such high-valued ω-7 FA only has a trace level in mature seeds of cotton and other common oil crops. We found that palmitoleic acid (>10.58 Mol%) was specially enriched in developing cotton endosperm which is disappeared in its mature seed. The present study was conducted to investigate the mechanism underlying high accumulation of palmitoleic acid in developing endosperm but not in embryo of upland cotton (Gossypium hirsutum L.) seed. Of 17 stearoyl-ACP Δ9 desaturases (SAD) gene family members identified in upland cotton, six GhSADs may specifically work in the desaturation of palmitic acid (16:0-ACP) to produce palmitoleic acid (16:1Δ9-ACP), which were revealed by examining the key amino acids in the catalytic center and their cis-elements. Gene expression analysis showed that spatial patterns of these GhSADs were different in developing ovules, with GhA-SAD6 and GhD-SAD8 preferentially expressed in developing endosperms. Functional analysis by transient expression in Nicotiana benthamiana leaves and genetic complementary assay using yeast mutant BY4389 strain unable to synthesize unsaturated fatty acids demonstrated that GhA-SAD6 and GhD-SAD8 have strong substrate specificity for 16:0-ACP. In contrast, GhA-SAD5 and GhA-SAD7 exhibited high specific activity on 18:0-ACP. Taken together, these data evidence that GhA-SAD6 and GhD-SAD8 are responsible for making palmitoleic acid in developing cotton endosperms, and provide endogenous gene targets for genetic modification to enrich ω-7 FAs in cotton seed oil required for sustainable production of functionality-valued products.

After liver transplantation, the liver function of a patient is gradually restored over a period of time that can be divided into a convalescence period (CP) and a stabilizing period (SP). The plasma concentration of tacrolimus, an immunosuppressant commonly used to prevent organ rejection, varies as a result of variations in its metabolism. The effects of genetic and clinical factors on the plasma concentration of tacrolimus appear to differ in the CP and SP. To establish a model explaining the variation in tacrolimus trough concentration between individuals in the CP and SP, we conducted a retrospective, single-center, discovery study of 115 pairs of patients (115 donors and 115 matched recipients) who had undergone liver transplantation. Donors and recipients were genotyped by a genome-wide association study (GWAS) using an exome chip. Novel exons were identified that influenced tacrolimus trough concentrations and were verified with bootstrap analysis. In donors, two single-nucleotide polymorphisms showed an effect on the CP (rs1927321, rs1057192) and four showed an effect on the SP (rs776746, rs2667662, rs7980521, rs4903096); in recipients, two single-nucleotide polymorphisms showed an effect in the SP (rs7828796, rs776746). Genetic factors played a crucial role in tacrolimus metabolism, accounting for 44.8% in the SP, which was higher than previously reported. In addition, we found that CYP3A5, which is known to affect the metabolism of tacrolimus, only influenced tacrolimus pharmacokinetics in the SP.

Irreversible electroporation (IRE) has been demonstrated to be a safe and effective method for locally advanced pancreatic cancer (LAPC). The aim of this study was to evaluate the immunomodulatory effect after IRE and to evaluate the prognostic value of variations of the immune parameters in LAPC patients after IRE.

Epilepsy is a neuronal disorder that is characterized by epileptic seizures and linked with abnormal neural functioning in the brain. Traditional Chinese medicine (TCM) formula Chaibei Zhixian decoction (CZD) has been widely used for epilepsy in China while the pharmacological mechanisms are still unclear. In the present study, systematic and comprehensive network pharmacology was utilized for the first time to reveal the potential pharmacological mechanisms of CZD on epilepsy.

Endothelin-1 (ET-1) is synthesized primarily by endothelial cells. ET-1 administration in vivo enhances the cardiac sympathetic afferent reflex and sympathetic activity. Previous studies have shown that sympathetic hyperactivity promotes malignant ventricular arrhythmia (VA). The aim of this study was to investigate whether ET-1 could activate the left stellate ganglion (LSG) and promote malignant VA. Twelve male beagle dogs who received local microinjections of saline (control, n = 6) and ET-1 into the LSG (n = 6) were included. The ventricular effective refractory period (ERP), LSG function, and LSG activity were measured at different time points. VA was continuously recorded for 1 h after left anterior descending occlusion (LADO), and LSG tissues were then collected for molecular detection. Compared to that of the control group, local ET-1 microinjection significantly decreased the ERP and increased the occurrence of VA. In addition, local microinjection of ET-1 increased the function and activity of the LSG in the normal and ischemic hearts. The expression levels of proinflammatory cytokines and the protein expression of c-fos and nerve growth factor (NGF) in the LSG were also increased. More importantly, endothelin A receptor (ETA-R) expression was found in the LSG, and its signaling was significantly activated in the ET-1 group. LSG activation induced by local ET-1 microinjection aggravates LADO-induced VA. Activated ETA-R signaling and the upregulation of proinflammatory cytokines in the LSG may be responsible for these effects.

Myocardial infarction (MI) is caused by extensive myocardial damage attributed to the occlusion of coronary arteries. Our previous study in a rat model of ischemia/reperfusion (I/R) demonstrated that administration of arabinoxylan (AX), comprising arabinose and xylose, protects against myocardial injury. In this study, we undertook to investigate whether psyllium seed husk (PSH), a safe dietary fiber containing a high level of AX (> 50%), also imparts protection against myocardial injury in the same rat model.

Since the adoption of free obstetric care policy in Guinea in 2011, no study has examined the surgical site infections in maternity facilities. The objective of this study was to assess the trends of and factors associated with surgical site infection following cesarean section in Guinean maternity facilities from 2013 to 2015. This was a retrospective cohort study using routine medical data from ten facilities. Overall, the incidence of surgical site infections following cesarean section showed a declining trend across the three periods (10% in 2013, 7% in 2014 and 5% in 2015, P<0.001). Women who underwent cesarean section in 2014 (AOR: 0.70; 95%CI: 0.57-0.84) and 2015 (AOR: 0.43; 95%CI: 0.34-0.55) were less likely to develop surgical site infections during hospital stay than women operated in 2013. In the contrary, women with comorbidities were more likely to experience surgical site infection (AOR: 1.54; 95% CI: 1.25-1.90) than those who did not have comorbidities. The reductions achieved in 2014 and 2015 (during the Ebola outbreak) should be sustained in the post-Ebola context.

The medially spherical GMK Sphere (Medacta International AG, Castel San Pietro, Switzerland) total knee arthroplasty (TKA) was previously shown to accommodate lateral rollback while pivoting around a stable medial compartment, aiming to replicate native knee kinematics in which some coronal laxity, especially laterally, is also present. We assess coronal plane kinematics of the GMK Sphere and explore the occurrence and pattern of articular separation during static and dynamic activities.

Platelet-rich fibrin matrix (PRFM) has been proved to enhance tenocyte proliferation but has mixed results when used during rotator cuff repair. The optimal PRFM preparation protocol should be determined before clinical application. To screen the best PRFM to each individual's tenocytes effectively, small-diameter culture wells should be used to increase variables. The gelling effect of PRFM will occur when small-diameter culture wells are used. A co-culture device should be designed to avoid this effect.

An ambition of healthcare policy has been to move more acute services into community settings. This systematic literature review presents analysis of published operational research methods for modelling patient flow within community healthcare, and for modelling the combination of patient flow and outcomes in all settings. Assessed for inclusion at three levels - with the references from included papers also assessed - 25 "Patient flow within community care", 23 "Patient flow and outcomes" papers and 5 papers within the intersection are included for review. Comparisons are made between each paper's setting, definition of states, factors considered to influence flow, output measures and implementation of results. Common complexities and characteristics of community service models are discussed with directions for future work suggested. We found that in developing patient flow models for community services that use outcomes, transplant waiting list may have transferable benefits.

Background: Multigene signatures refine the risk of recurrence and guide adjuvant chemotherapy decision in luminal breast cancers. The decision to perform the assay is highly variable among oncologists. In order to guide the appropriate clinical group in whom to perform a genomic signature, our study analyzed in a homogeneous cohort which clinical risk groups triggered the use of the PAM50-based signature and their concordance with the genomic risk. Methods: A real life cohort of 222 early breast cancer patients with hormone receptor positive and HER2 negative disease had a commercial PAM50-based assay (Prosigna®) performed at our institution. The assay provided the risk group, the 10-year risk of distant recurrence and the intrinsic molecular subtype of breast cancer. Results: Based on nodal involvement, Ki67, tumor grade, mitotic index, and tumor size, no clinical pattern could identify a specific genomic risk group. The discordance with the genomic risk was high in patients with clinical low risk tumors, both in node negative and node positive patients. Up to 60% of them had a 10% or more risk of distant recurrence. Moreover, we identified a subgroup of luminal A tumors with a high genomic risk of recurrence. Genomic risk and intrinsic subtype were strong determinants of chemotherapy decision. Conclusions: Clinical profiles could not reliably identify genomic risk groups and guide the decision to use a multigene signature. Significant discordance with the genomic risk was observed within low clinical risk and luminal A tumors.

Over the last decade, the use of targeted therapies has immensely increased in the treatment of cancer. However, treatment for endometrial carcinomas (ECs) has lagged behind, although potential molecular markers have been identified. This is particularly problematic for the type II ECs, since these aggressive tumors are usually not responsive toward the current standard therapies. Therefore, type II ECs are responsible for most EC-related deaths, indicating the need for new treatment options. Interestingly, molecular analyses of type II ECs have uncovered frequent genetic alterations (up to 40%) in PPP2R1A, encoding the Aα subunit of the tumor suppressive heterotrimeric protein phosphatase type 2A (PP2A). PPP2R1A mutations were also reported in type I ECs and other common gynecologic cancers, albeit at much lower frequencies (0-7%). Nevertheless, PP2A inactivation in the latter cancer types is common via other mechanisms, in particular by increased expression of Cancerous Inhibitor of PP2A (CIP2A) and PP2A Methylesterase-1 (PME-1) proteins. In this review, we discuss the therapeutic potential of direct and indirect PP2A targeting compounds, possibly in combination with other anti-cancer drugs, in EC. Furthermore, we investigate the potential of the PP2A status as a predictive and/or prognostic marker for type I and II ECs.

Hypoxia is a key driver of tumor adaptation promoting tumor progression and resistance to therapy. Hypoxia related pathways might represent attractive targets for the treatment of Glioblastoma Multiforme (GBM), that up to date is characterized by a poor prognosis. Primary aim of this study was to investigate the role of hypoxia and hypoxia-related modifications in the effect of temozolomide (TMZ) given alone or in association with the antidiabetic agent Metformin (MET) or the PI3K/mTOR blocker, BEZ235. The study was conducted in the TMZ responsive U251 and resistant T98 GBM cells. Our results showed that during hypoxia, TMZ plus MET reduced viability of U251 cells affecting also CD133 and CD90 expressing cells. This effect was associated with a reduction of HIF-1α activity, VEGF release and AKT activation. In T98 TMZ-resistant cells, TMZ plus MET exerted similar effects on HIF-1α. However, in this cell line, TMZ plus MET failed to reduce CD133 positive cells and AKT phosphorylation. Nevertheless, the administration of the dual PI3K/mTOR inhibitor BEZ235 potentiated the effect of TMZ plus MET on cell viability, inducing a pro-apoptotic phenotype during hypoxic condition also in T98 cells, suggesting the block of the PI3K/AKT/mTOR pathway as a complementary target to further overcome GBM resistance during hypoxia. In conclusion, we proposed TMZ plus MET as suitable treatment to revert TMZ-resistance also during hypoxia, an effect potentiated by the inhibition of PI3K/mTOR axis.

The current study investigated the combination of high Z atoms (iodine-, platinium-based drugs) with using low energy irradiation (120kvp) in Anaplastic Thyroid cancer cells.

Objectives: To retrospectively investigate the impact of supervised daily nasal saline irrigations (NSI) with 0. 9% saline solution in children with a history of recurrent acute otitis media (RAOM). Methods: A retrospective pilot study was planned to evaluate the possible effect of supervised NSI in reducing the number of acute otitis media (AOM) episodes in otitis-prone children aged 1-5 years, compared to children not instructed to correct NSI performance. Results: Analysis was based on the data contained in 173 charts (57.3% males, mean age of 30.9 ± 7.3 months). 52.0% of children had not been instructed to perform NSI, while the remaining (48.0%) patients had received supervised NSI. At the 4-months follow-up visit a significant reduced number of AOM episodes (1.03 ± 0.14 vs. 2.08 ± 0.16; p < 0.001) as well as antibiotic treatments (1.48 ± 0.17 vs. 2.59 ± 0.18; p < 0.001) was documented in children receiving supervised NSI compared to those not instructed for NSI performance. Conclusions: These data suggest that NSI should be considered in the therapeutic management of children with RAOM, and should be routinely prescribed as a daily adjunctive treatment to reduce acute infectious exacerbations in otitis-prone patients. Accurate parents training is crucial in order to improve children compliance and treatment effectiveness.

Abdominal aortic aneurysm (AAA) is the dilatation of the aorta beyond 50% of the normal vessel diameter. It is reported that 4-8% of men and 0.5-1% of women above 50 years of age bear an AAA and it accounts for ~15,000 deaths per year in the United States alone. If left untreated, AAA might gradually expand until rupture; the most catastrophic complication of the aneurysmal disease that is accompanied by a striking overall mortality of 80%. The precise mechanisms leading to AAA rupture remains unclear. Therefore, characterization of disturbed hemodynamics within AAAs will help to understand the mechanobiological development of the condition which will contribute to novel therapies for the condition. Due to geometrical complexities, it is challenging to directly quantify disturbed flows for AAAs clinically. Two other approaches for this investigation are computational modeling and experimental flow measurement. In computational modeling, the problem is first defined mathematically, and the solution is approximated with numerical techniques to get characteristics of flow. In experimental flow measurement, once the setup providing physiological flow pattern in a phantom geometry is constructed, velocity measurement system such as particle image velocimetry (PIV) enables characterization of the flow. We witness increasing number of applications of these complimentary approaches for AAA investigations in recent years. In this paper, we outline the details of computational modeling procedures and experimental settings and summarize important findings from recent studies, which will help researchers for AAA investigations and rupture mechanics.

Biomaterials play a critical role in technologies intended to deliver therapeutic agents in clinical settings. Recent explosion of our understanding of how cells utilize nucleic acids has garnered excitement to develop a range of older (e.g., antisense oligonucleotides, plasmid DNA and transposons) and emerging (e.g., short interfering RNA, messenger RNA and non-coding RNAs) nucleic acid agents for therapy of a wide range of diseases. This review will summarize biomaterials-centered advances to undertake effective utilization of nucleic acids for therapeutic purposes. We first review various types of nucleic acids and their unique abilities to deliver a range of clinical outcomes. Using recent advances in T-cell based therapy as a case in point, we summarize various possibilities for utilizing biomaterials to make an impact in this exciting therapeutic intervention technology, with the belief that this modality will serve as a therapeutic paradigm for other types of cellular therapies in the near future. We subsequently focus on contributions of biomaterials in emerging nucleic acid technologies, specifically focusing on the design of intelligent nanoparticles, deployment of mRNA as an alternative to plasmid DNA, long-acting (integrating) expression systems, and in vitro/in vivo expansion of engineered T-cells. We articulate the role of biomaterials in these emerging nucleic acid technologies in order to enhance the clinical impact of nucleic acids in the near future.

Arterial catheters are used for intraoperative continuous direct blood pressure monitoring in dogs. Factors such as bending and occlusion of the cannula are believed to be involved in direct blood pressure measurement failure. However, no method has been proposed to improve the maintenance of arterial catheter patency in veterinary medicine. The aim of this pilot study was to evaluate the patency of arterial catheters when using an arterial catheter securement device in the dorsal pedal artery of dogs under general anesthesia. Client-owned dogs (n = 120) were anesthetized for surgical procedures, during which direct arterial blood pressure was monitored using an arterial catheter secured with conventional film dressing and medical tape. A securement device, allowing an angle of 12.5° to the skin surface of the dorsal pedal area, was used in 50% of the dogs (n = 60). Significant reductions were observed in the frequency of catheter flushing and rate of occlusion in the experimental group compared to the control group (13.3 vs. 35.0%, relative risk [RR]: 0.381, 95% confidence interval [CI]: 0.183-0.792, P = 0.001 and 8.3 vs. 23.3%, RR: 0.376, 95% CI: 0.145-0.977, P = 0.044, respectively). The Kaplan-Meier curves for assessing the probability of occlusion were significantly different between the groups (P = 0.042). In conclusion, this pilot study suggests that the novel arterial catheter securement device is effective for achieving stable securement of the catheter hub in the dorsal pedal artery and for maintaining a longer duration of arterial catheter patency in dogs under general anesthesia. Therefore, the use of an arterial catheter securement device in the dorsal pedal artery of dogs would be useful for continuous hemodynamic monitoring and improve patient safety when direct arterial blood pressure monitoring is required in dogs undergoing general anesthesia.

Small ruminant lentiviruses (SRLVs) belong to the genus Lentivirus in the Retroviridae family. There are five genotypes (A, B, C, D, and E), where genotypes A and B have a global distribution and genotypes C, D, and E are limited to Europe. The presence of SRLV has been confirmed in Mexico, with genotype B detected in the central region of the country. We examined the presence of SRLVs and genotype prevalence in 1014 sheep and 1383 goats from 12 Mexican states. Using a commercial competitive ELISA (cELISA) test, we detected SRLV antibodies in 107 sheep (10.55%) and 466 goats (33.69%). We used an endpoint PCR to amplify the LTR region on seropositive animals. A total of 50 sheep and 75 goats tested positive via PCR. Positive amplicons from 11 sheep and 17 goats from ten Mexican States were cloned and sequenced. With the LTR sequence data obtained in this study, a phylogenetic analysis was performed; we also constructed a phylogenetic tree using the obtained sequences and GenBank's available sequences. All studied sequences were associated with genotype B, specifically with the FESC-752 isolate previously identified in Mexico. Highly conserved transcription factor binding sites were observed in analyzed alignments, such as AML (vis), AP-4, and TATA box. However, we identified nucleotide differences at site AP-1 that suggest function loss. Our study found that ovine and caprine genotype B SRLVs are widely distributed in Mexico; a highly conserved LTR region among the sequences evaluated in this study was also found.