Biotrophic pathogens, such as the related maize pathogenic fungi Ustilago maydis and Sporisorium reilianum, establish an intimate relationship with their hosts by secreting protein effectors. Because ...secreted effectors interacting with plant proteins should rapidly evolve, we identified variable genomic regions by sequencing the genome of S. reilianum and comparing it with the U. maydis genome. We detected 43 regions of low sequence conservation in otherwise well-conserved syntenic genomes. These regions primarily encode secreted effectors and include previously identified virulence clusters. By deletion analysis in U. maydis, we demonstrate a role in virulence for four previously unknown diversity regions. This highlights the power of comparative genomics of closely related species for identification of virulence determinants.
In the phytopathogenic fungus Ustilago maydis a conserved mitogen-activated-protein-kinase (MAPK) module regulates sexual and pathogenic development. Kpp2 is the central MAPK of this module and is ...required for transcriptional and morphological responses to pheromone. Upon perception of the pheromone signal Kpp2 is phosphorylated by the MAPK kinase Fuz7. Here we demonstrate that the MAPK Kpp6, which has a partially redundant function with Kpp2, is also phosphorylated by Fuz7. We show that Rok1, a putative dual specificity phosphatase for MAPK signalling, controls the phosphorylation of Kpp2 as well as of Kpp6. rok1 mutants display increased filamentation and are enhanced in virulence. The enhanced virulence is caused by more efficient appressorium formation as well as plant invasion. Overexpression of rok1 reduced conjugation hyphae formation and strongly attenuated pathogenicity. This places Rok1 in a negative feedback loop regulating Kpp2 and Kpp6 activity upon pheromone stimulation and plant colonization.
Background Fluctuating asymmetry (FA) is widely defined as the deviation from perfect bilateral symmetry and is considered an epigenetic measure of environmental stress. Rinaldi and Fontani ...hypothesized that the FA morpho-functional changes originate from an adaptive motor behavior determined by functional alterations in the cerebellum and neural circuits, not caused by a lesion, but induced by environmental stress. They called this phenomenon functional dysmetria (FD). On this premise, they developed the radio electric asymmetric conveyer (REAC) technology, a neuromodulation technology aimed at optimizing the best neuro-psycho-motor strategies in relation to environmental interaction. Aims Previous studies showed that specific REAC neuro postural optimization (NPO) treatment can induce stable FD recovery. This study aimed to verify the duration of the NPO effect in inducing the stable FD recovery over time. Materials and methods Data were retrospectively collected from a population of 29,794 subjects who underwent a specific semiological FD assessment and received the NPO treatment, regardless of the pathology referred. Results The analysis of the data collected by the various participants in the study led us to ascertain the disappearance of FD in 100% of the cases treated, with a stability of the result detected up to 18 years after the single administration of the REAC NPO treatment. Conclusions The REAC NPO neurobiological modulation treatment consisting of a single administration surprisingly maintains a very long efficacy in the correction of FD. This effect can be explained as the long-lasting capacity of the NPO treatment to induce greater functional efficiency of the brain dynamics as proven in previous studies.
OBJECTIVES
To evaluate, in a prospective and randomized fashion, the efficacy of a pretreatment with verapamil (V) in reducing recurrences of atrial fibrillation (AF) after electrical cardioversion ...(C).
BACKGROUND
The increased vulnerability for AF recurrence is probably due to AF-induced changes in the electrophysiologic properties of the atria. This electrical remodeling seems to be due to intracellular calcium overload.
METHODS
One hundred seven patients with persistent or chronic AF underwent external and/or internal C. All patients received oral propafenone (P) (900 mg/day) three days before and during the entire period of follow-up (three months). In the first group, patients received only the P. In the second group, in adjunct to P, oral V (240 mg/day) was initiated three days before C and continued during the follow-up. Finally, in the third group, oral V was administered three days before and continued only for three days after electrical C.
RESULTS
During the three months of follow-up, 23 patients (23.7%) had AF recurrence. Mantel-Haenszel cumulative chi-square reached a significant level only when comparing AF free survival curves of group I versus group II and group III (chi-square = 5.2 and 4, respectively; p < 0.05). Significantly, 15 (65.2%) AF relapses occurred during the first week after cardioversion with a higher incidence in group I (10/33 patients, 30.3%) than group II (2/34 patients, 5.9%; p = 0.01) and group III (3/30 patients, 10%; p = 0.04).
CONCLUSIONS
Six days of oral V administration centered on the C day, combined with P, significantly reduce the incidence of early recurrences of AF compared with P alone.
AIM To assess the rate of matrix Gla-protein carboxylation in patients with small intestinal bacterial overgrowth(SIBO) and to decipher its association with subclinical atherosclerosis.METHODS ...Patients with suspected SIBO who presented with a low risk for cardiovascular disease and showed no evidence of atherosclerotic plaques were included in the study. A glucose breath test was performed in order to confirm the diagnosis of SIBO and vascular assessment was carried out by ultrasound examination. Plasma levels of the inactive form of MGP(dephosphorylateduncarboxylated matrix Gla-protein) were quantified by ELISA and vitamin K2 intake was estimated using a food frequency questionnaire.RESULTS Thirty-nine patients were included in the study. SIBO was confirmed in 12/39(30.8%) patients who also presented with a higher concentration ofdephosphorylated-uncarboxylated matrix Gla-protein(9.5 μg/L vs 4.2 μg/L; P = 0.004). Arterial stiffness was elevated in the SIBO group(pulse-wave velocity 10.25 m/s vs 7.68 m/s; P = 0.002) and this phenomenon was observed to correlate linearly with the levels of dephosphorylated-uncarboxylated matrix Gla-protein(β = 0.220, R2 = 0.366, P = 0.03). Carotid intima-media thickness and arterial calcifications were not observed to be significantly elevated as compared to controls.CONCLUSION SIBO is associated with reduced matrix Gla-protein activation as well as arterial stiffening. Both these observations are regarded as important indicators of subclinical atherosclerosis. Hence, screening for SIBO, intestinal decontamination and supplementation with vitamin K2 has the potential to be incorporated into clinical practice as additional preventive measures.
In the field of infrastructure, the development and application of the openBIM (open Building Information Modeling) approach and related standards (principally Industry Foundation Classes) remain ...limited with regard to processes in O&M (Operation and Maintenance) phases, as well as the broader context of AM (Asset Management). This article deals with the activities carried out as part of a pilot project based on the need to manage the operation and assess the condition and value of existing infrastructure along the Cancello–Benevento railway line. The principal goal was to systematize information by digitalizing the infrastructure, in order to enable the assessment of possible performance gaps (compared to national railway standards) in the event of integration within the national infrastructure. In compliance with the project requirements, a digitalization strategy was designed for the definition of surveying activities and the implementation of openBIM systems for the development of an object library and a federated digital model, structured within the collaborative platform that was used, and allowing management, maintenance, and subsequent financial evaluation in the broader context of asset management. The project involved the collaboration of railway operators, a university, and a software company that implemented innovative concepts concerning IFC (specifically, IFC4x2 was used) through the development of dedicated software solutions. The digital solution we proposed enabled the use of digital models as access keys to survey and maintenance information (ERP platforms used by the railway operators) that was available in real time. This project was nominated at the buildingSMART awards 2021 and was one of three finalists in the “Asset Management Using openBIM” category.
Abstract Background and Aims In many patients on chronic hemodialysis, interdialytic weight gain (IDWG) is greater than 4.0%-4.5% of dry weight, the value recommended by the international guidelines. ...High IDWG is a condition associated with risk of all-cause mortality and hospitalization and it depends on elevate intake of fluids and/or foods. More specifically, high intake of water is secondary to the disturbing and constant presence of thirst in such patients, so the limitation of the IDWG is a challenge both for the patients and the physicians. Low dialysate sodium levels can significantly reduce thirst as well as the water intake in the interdialytic period because they can increase the removal of sodium during the dialytic session, and this leads to a reduced content of sodium in the body. The present systematic review and meta-analysis aims at evaluating the efficacy of low dialysate sodium concentration on interdialytic weight gain (IDWG) in chronic hemodialysis patients. Method Studies were eligible for inclusion if they were English language papers published in a peer-reviewed journal and met the following inclusion criteria: 1) Primary research studies in adult patients (over 18 years of age), 2) Included patients with end-stage renal disease on chronic hemodialysis since at least 6 months; 3) Compared standard (138-140 mmol/l) or high (>140 mmol/l) dialysate sodium concentration with low (<138 mmol/l) dialysate sodium concentration; 4) Included one outcome of interest: interdialytic weight gain. We excluded studies on pediatric patients, pre-dialysis CKD patients, acute kidney injury patients, ESRD patients with other renal replacement therapy modalities such as peritoneal dialysis and transplant. Medline, PubMed, Web of Science, and the Cochrane Library were searched for studies comparing low or high dialysate sodium concentration. Outcome of interest was IDWG. The quality of reporting for each study was performed using the Quality Assessment Tool of Controlled Intervention Studies of the National Institutes of Health. The quality of reporting of each cross-over study was performed using the Revised Cochrane Risk of Bias (RoB) tool for cross-over trials as proposed by Ding et al. Results Nineteen studies (710 patients) were included in the analysis: 15 were cross-over and 4 parallel randomized controlled studies. In cross-over studies, pooled analysis revealed that dialysate sodium concentration reduced IDWG with a pooled MD of −0.40 kg (95% CI -0.50 to −0.30; P < 0.00001). The systematic review of four parallel, randomized, studies revealed that the use of a low dialysate sodium concentration was associated with a significant reduction of the IDWG in two studies, sustained and almost significant (P=0.05) reduction in one study, and not significant reduction in one study. In most studies, the frequency of intradialytic hypotensive events did not differ significantly between low and high sodium dialysate hemodialysis. The GRADE methodology was used to assess the quality of the body of retrieved evidence and studies risk of bias, inconsistency and imprecision were estimated as low. Conclusion Low dialysate sodium concentration reduces the IDWG in patients on chronic hemodialysis.
Abstract Background and Aims Chronic hemodialysis is often associated with post-dialysis fatigue (PDF), a condition characterized by extreme tiredness and lack of energy. PDF is a debilitating ...symptom that significantly impairs quality of life of hemodialysis patients. Furthermore, PDF is independently associated with the time to recover after dialysis (TIRD), which can be used as an indirect measure of PDF. Recent studies have shown that the use of proton pump inhibitors (PPI) is independently associated with the prevalence and severity of fatigue in kidney transplant recipients. The aim of this study is to determine whether the use of PPIs in patients undergoing chronic hemodialysis is associated with PDF prevalence and characteristics, as well as the TIRD. Method For this retrospective study, we recruited patients undergoing chronic hemodialysis and asked open-ended questions about their post-dialysis fatigue and time of recovery. Each patient was asked to rate the intensity, duration and frequency of their PDF on a scale of 1 to 5. We defined whether patients used a PPI (no PPI use or PPI use), the type of PPI used, the dose of PPI used, and the duration of the PPI use (<1 year or ≥1year). Results The study analysed 346 patients, of whom 259 used PPIs (55 used omeprazole, 63 esomeprazole, 54 pantoprazole, 87 lansoprazole, and 7 rabeprazole) and 87 did not. Among the patients, 232 reported suffering from PDF, while 114 did not. The median min-max TIRD was 210 minutes 0-1440. The prevalence of PDF in PPI users and non-users was 67% and 68%, respectively (p= 0.878). There was no significant difference in the median min-max TIRD between PPI users and non-users (180 0-1440 and 240 0-1440, respectively; p=0.871). Additionally, there was no significant difference in the median PDF intensity, duration, frequency, and severity PPI users and non-users. The prevalence of PDF was similar among the different types of PPI used and did not differ with respect to PPI non-users. Duration of PPI exposure was <1 year in 42 patients and ≥1 year in 224 patients. There was no difference in prevalence of PDF between the two exposures. The correlation matrix showed no statistical significance between PPI equivalent dose, treatment duration, PDF frequency, PDF characteristics, and TIRD. Conclusion There is no association between the use of PPIs and PDF or time of recovery after dialysis in patients on chronic hemodialysis.
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