Low Molecular Weight and High Deacetylation Degree Chitosan Batch Alleviates Pathogenesis, Toxin Accumulation, and Fusarium Gene Regulation in Barley Leaf Pathosystem.

Fusarium graminearum is a cosmopolitan fungal pathogen that destroys cereal production, in terms of loss of yield and grain contamination with mycotoxins, worldwide. Chitosan is a natural biopolymer abundant in the environment with proven antifungal properties that also acts as a plant immunity elicitor. Despite a number of articles, there is a lack of systematic comparison of antifungal activity of diverse batches of chitosan. The current study aimed to test the inhibitory effects of a collection of diverse chitosan samples on the growth and production of F. graminearum toxins, validated by changes in the Fusarium transcriptome. Experiments included testing antifungal activity of different chitosan samples, the application of the best performing one in vitro to investigate the impact on F. graminearum growth, followed by analyzing its effect on Fusarium toxins accumulation, and Fusarium transcriptomics in the barley leaf pathosystem. Confirmatory antifungal assays revealed that CS_10, a specific batch of chitosan, retarded Fusarium growth with an application concentration of 200 ppm, significantly reducing toxin synthesis and disease symptoms in Fusarium-inoculated barley leaves. RNA-Seq analysis of F. graminearum in barley leaf pathosystem exposed to CS_10 showed a list of differentially expressed genes involved in redox balance, cell respiration, nutrient transport, cell wall degradation enzymes, ergosterol biosynthesis, and trichothecenes production. The genes functioning in these essential pathways are discussed and assigned as critical checkpoints to control Fusarium infections. The results suggest some important molecular targets in F. graminearum that may be suitable in gene-specific targeting or transgene-free methods, such as spray-induced gene silencing during host-pathogen interactions.

Chitosan and Chitosan Nanoparticles: Parameters Enhancing Antifungal Activity.

Chitosan (CS), a biopolymer derived from chitin, is known for strong antifungal activity while being biodegradable, biocompatible, and non-toxic. Because of its characteristic it has been widely used in control of fungal pathogens. Antifungal activity of chitosan can be further enhanced by obtaining chitosan nanoparticles (CSNPs). However, most of the experiments using CS and CSNPs as antifungal agents were performed under various conditions and using diverse CS batches of different characteristics and obtained from different sources. Therefore, it is essential to systematize the available information. This work contains a current review on how the CS parameters: molecular weight, degree of deacetylation, acetylation pattern and dispersity of these features shape its antifungal activity. It also considers how concentration and protonation (pH) of CS water solutions define final biological effect. Review explains in detail how CS parameters affect characteristics of CSNPs, particle size, zeta potential, and dispersities of both and determine antifungal activity. In addition to the parameters of CS and CSNPs, the review also discusses the possible characteristics of fungal cells that determine their susceptibility to the substances. The response of fungi to CS and CSNPs varies according to different fungal species and their stages of development. The precise knowledge of how CS and CSNP parameters affect specific fungal pathogens will help design and optimize environmentally friendly plant protection strategies against fungi.

Newly Diagnosed Monostotic Paget's Disease of Bone during Living Kidney Donor Candidate Evaluation.

The popularity of living-donor organ donation has increased recently as an alternative to deceased-organ donation due to the growing need for organs and a shortage of deceased-donor organs. This procedure requires an in-depth health assessment of candidates, who must be in excellent physical and mental health. We present a potential living-kidney donor withdrawn from donation due to a newly diagnosed Paget's disease of bone (PDB). The patient underwent computed tomography (CT), magnetic resonance imaging (MRI), bone scintigraphy, and bone densitometry with trabecular bone score (TBS) assessment. The sole lumbar vertebra affected by PDB was investigated comprehensively, non-invasively, quantitatively, and qualitatively.

Barley Resistance to Fusarium graminearum Infections: From Transcriptomics to Field with Food Safety Concerns.

Global climate change and the urgency to transform food crops require substantial breeding efforts to meet the food security challenges. Barley, an important cereal, has remained a preferential host of phytotoxic diseases caused by the Fusarium graminearum that not only severely reduces the crop yield but also compromises its food quality due to the accumulation of mycotoxins. To develop resistance against Fusarium infections, a better understanding of the host-pathogen interaction is inevitable and could be tracked through molecular insights. Here, we focused precisely on the potential gene targets that are exclusive to this devastating pathosystem and could be harnessed for fast breeding of barley. We also discuss the eco-friendly applications of nanobio hybrid and the CRISPR technology for barley protection. This review covers the critical information gaps within the subject and may be useful for the sustainable improvement of barley from the perspective of food and environmental safety concerns.

Graph Pangenomes Track Genetic Variants for Crop Improvement.

Global climate change and the urgency to transform crops require an exhaustive genetic evaluation. The large polyploid genomes of food crops, such as cereals, make it difficult to identify candidate genes with confirmed hereditary. Although genome-wide association studies (GWAS) have been proficient in identifying genetic variants that are associated with complex traits, the resolution of acquired heritability faces several significant bottlenecks such as incomplete detection of structural variants (SV), genetic heterogeneity, and/or locus heterogeneity. Consequently, a biased estimate is generated with respect to agronomically complex traits. The graph pangenomes have resolved this missing heritability and provide significant details in terms of specific loci segregating among individuals and evolving to variations. The graph pangenome approach facilitates crop improvements through genome-linked fast breeding.

Molnupiravir When Used Alone Seems to Be Safe and Effective as Outpatient COVID-19 Therapy for Hemodialyzed Patients and Kidney Transplant Recipients.

BACKGROUND: Molnupiravir demonstrated an in vitro antiviral activity against positive-sense RNA viruses, including SARS-CoV-2. The study aimed to present the results of outpatient molnupiravir use in kidney transplant recipients and hemodialysis patients during the first months of 2022 in Poland. METHODS: The retrospective observational cohort study at one kidney transplant center included 36 patients diagnosed with COVID-19 with an automated nucleic acid amplification test on nasopharyngeal swab specimens. All patients received molnupiravir for home-based therapy at a dose of 800 mg every 12 h orally for 5 days. Both kidney transplant recipients (n = 16) and hemodialysis patients (n = 20) presented a lot of comorbidities with a Charlson comorbidity index of 4.1 and 5.1, respectively. RESULTS: Patients presented with fever, cough, and weakness followed by muscle and joint pain. Five kidney transplant recipients experienced acute kidney injury with a rise in serum creatinine level from 0.4 to 1.9 mg/dL. No serious side effects of molnupiravir therapy or interactions with immunosuppressive medications were observed. Symptoms of COVID-19 improved rapidly or resolved within 24-48 h of starting treatment. CONCLUSION: The study suggests the safety and efficacy of molnupiravir therapy alone early after the onset of SARS-CoV-2 infection, but further investigations should be performed to confirm our preliminary results. To the best of the authors' knowledge, it is the first published report on molnupiravir use in end-stage kidney disease (ESKD) patients on hemodialysis and the third concerning kidney transplant recipients.

Psychopathological Symptoms Among Chronically Ill Patients During SARS-CoV-2 Pandemic in Poland.

Introduction: The global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic had a drastic psychological and economic impact on the global population. Having a chronic disease during the pandemic is associated with numerous limitations and challenges like regular hospital visits, access to health-care units and getting specialized treatment. In addition, chronically ill patients are at great risk of acquiring the SARS-CoV-2 virus and at experiencing a more severe course of illness, due to comorbid conditions as well as more frequent encounters with health-care workers and other patients in medical facilities. The aim of this study was to examine the psychological disturbances, during the pandemic in chronically ill patients. Methods: During the cross-sectional survey conducted between May and October 2020, 398 patients with four different chronic conditions (psoriasis, multiple sclerosis and patients who have undergone a kidney transplant or received dialysis). Study sample was examined regarding the occurrence of psychopathological symptoms (General Health Questionnaire 28) and their perceived stress levels (Perceived Stress Scale). Results: The highest scores were found in the MS group and the lowest scores were found in the kidney transplantation group in every subscale of the GHQ-28. Close to half of the studied population (48.74%, n = 193) patients scored above the cut-off for psychopathology. Conclusion: As the study was conducted during the SARS-CoV-2 pandemic in Poland, it stands to reason that the pandemic affected the psychological wellbeing of chronically ill patients. A COVID-19 infection, being quarantined and having had contact with a person who was infected, did not significantly affect the outcome measures; however, further research is needed to explore this topic.

Immunity after COVID-19 Recovery and Vaccination: Similarities and Differences.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with a robust immune response. The development of systemic inflammation leads to a hyperinflammatory state due to cytokine release syndrome during severe COVID-19. The emergence of many new SARS-CoV-2 variants across the world deteriorates the protective antiviral immunity induced after infection or vaccination. The innate immune response to SARS-CoV-2 is crucial for determining the fate of COVID-19 symptomatology. T cell-mediated immunity is the main factor of the antiviral immune response; moreover, SARS-CoV-2 infection initiates a rapid B-cell response. In this paper, we present the current state of knowledge on immunity after COVID-19 infection and vaccination. We discuss the mechanisms of immune response to various types of vaccines (nucleoside-modified, adenovirus-vectored, inactivated virus vaccines and recombinant protein adjuvanted formulations). This includes specific aspects of vaccination in selected patient populations with altered immune activity (the elderly, children, pregnant women, solid organ transplant recipients, patients with systemic rheumatic diseases or malignancies). We also present diagnostic and research tools available to study the anti-SARS-CoV-2 cellular and humoral immune responses.

Acute kidney injury secondary to urinary tract infection in kidney transplant recipients.

Acute kidney injury (AKI) in kidney transplant recipients (KTRs) is a common, yet poorly investigated, complication of urinary tract infections (UTI) and urosepsis. A retrospective comparative analysis was performed, recruiting 101 KTRs with urosepsis, 100 KTRs with UTI, and 100 KTRs without history of UTI or sepsis. The incidences of AKI in the urosepsis and UTI groups were 75.2% and 41%, respectively. The urosepsis group has also presented with a significantly higher prevalence of AKI stage 2 and 3 than the UTI group. The rates of recovery from AKI stages 1, 2 and 3, were 75,6%, 55% and 26.1%, respectively. Factors independently associated with renal recovery from AKI were: AKI severity grade (AKI stage 2 with OR = 0.25 and AKI stage 3 with OR = 0.1), transfusion of red blood cells (RBC) (OR = 0.22), and the use of steroid bolus in the acute phase of treatment (OR = 4). The septic status (urosepsis vs UTI) did not influence the rates of renal recovery from AKI after adjustment for the remaining variables. The dominant cause of RBC transfusions in the whole population was upper GI-bleeding. In multivariable analyses, the occurrence of AKI was also independently associated with a greater decline of eGFR at 1-year post-discharge and with a greater risk of graft loss. In KTRs with both urosepsis and UTI, the occurrence of AKI portends poor transplantation outcomes. The local transfusion policy, modulation of immunosuppression and stress ulcer prophylaxis (which is not routinely administered in KTRs) in the acute setting may be modifiable factors that significantly impact long-term transplantation outcomes.

Is a Patient with Paget's Disease of Bone Suitable for Living Kidney Donation?-Decision-Making in Lack of Clinical Evidence.

Living donor kidney transplantation is a widely performed medical procedure. Living kidney donation requires an in-depth health assessment of candidates. The potential living kidney donor must remain healthy after kidney removal. A consequence of donation can be a decrease in glomerular filtration rate (GFR), and donors can become at risk of developing chronic kidney disease (CKD). We present a rationale for potential living kidney donor withdrawal due to Paget's disease of bone (PDB) based on a literature review. The treatment for PDB includes the use of, for example, non-steroidal anti-inflammatory drugs (NSAIDs), which can lead to acute kidney injury (AKI) as well as CKD, or bisphosphonates, which are not recommended for patients with decreased GFR.

Comparing Humoral and Cellular Adaptive Immunity during Convalescent Phase of COVID-19 in Hemodialysis Patients and Kidney Transplant Recipients.

BACKGROUND: It is still unclear whether COVID-19 convalescent kidney transplant recipients (KTR) and hemodialysis (HD) patients can develop anti-SARS-CoV-2 adaptive immunity. The aim was to characterize and compare the immune response to the virus in HD patients and KTR. METHODS: The study included 26 HD patients and 54 KTR-both convalescent (14 HD, 25 KTR) and unexposed. The immune response was assessed by determining the anti-SARS-CoV-2 antibodies in serum and specific T cell response via the interferon-gamma release assay (IGRA). Moreover, blood-morphology-derived parameters, immune cell phenotypes, and acute phase reactants were evaluated. RESULTS: KRT and HD convalescents presented similar serum levels of anti-SARS-CoV-2 IgG and IgA. A negative correlation occurred between IgG and time after the infection was observed. There was a strong relationship between the prevalence of anti-SARS-CoV-2 cellular and humoral responses in both groups. Convalescent IGRA response was significantly higher in HD patients compared to KTR. CONCLUSIONS: HD patients and KTR develop humoral and cellular responses after COVID-19. The antibodies levels are similar in both groups of patients. SARS-CoV-2-reactive T cell response is stronger in HD patients compared to KTR. The SARS-CoV-2-specific IgG level decreases with time while IgA and a cellular response are maintained. IGRA proved to be a valuable test for the assessment of specific cellular immunity in immunocompromised HD patients and KTR.

Immune Response to Vaccination against COVID-19 in Breastfeeding Health Workers.

BACKGROUND: Initially, there were no data on the safety of COVID-19 vaccines in lactating women. The aim of our study was to evaluate the immune response to COVID-19 vaccinations in breastfeeding women. METHODS: The study included 32 breastfeeding women who, regardless of the study, had decided to be vaccinated. Maternal serum and breast milk samples were simultaneously collected on days 8 ± 1, 22 ± 2, 29 ± 3, and 43 ± 4 after the first dose of the vaccine. The immune response was assessed by determining the presence of anti-SARS-CoV-2 IgG and IgA. RESULTS: The breast milk IgG level was detectable (6.50 ± 6.74, median 4.7, and maximum 34.2 BAU/mL) and highly correlated to serum IgG level (rS 0.89; p < 0.001). The breast milk ratio of IgA to the cut-off value was higher in serum IgA-positive (4.18 ± 3.26, median 2.8, and maximum >10) than in serum IgA-negative women (0.56 ± 0.37, median 0.5, and maximum 1.6; p < 0.001). The highest concentrations of serum and breast milk antibodies were observed on day 29 ± 3 with a decrease on day 43 ± 4. CONCLUSION: The immune response to the vaccination against SARS-CoV-2 is strongest 7 ± 3 days after the second dose of the vaccine. Lactating mothers breastfeeding their children after vaccination against SARS-CoV-2 may transfer antibodies to their infant.

Kidney Transplantation in COVID Pandemic-A Review of Guidelines.

The paper describes problems with the transplantation process during the COVID-19 pandemic. Transplantation procedures and programs have been impacted by COVID-19. The number of transplants has fallen noticeably. The first part of the paper points out changes in service organization, in particular donor and recipient pre-transplant and peri-transplant management. If the patients during pre-transplant evaluation need to attend face-to-face appointments, such as blood testing or other investigations, the risk of contracting or spreading COVID-19 should be minimized. "Clear green areas", which are COVID-19-free pathways, are highly recommended in hospitals during transplant procedures. Diagnostic procedures concerning donors, including CT scans and coronavirus testing (nasopharyngeal swab), are necessary before transplant surgery. COVID-19 symptoms and risks of the transplant population are described. Detailed guidelines from transplant societies concerning changes in immunosuppression in infected recipients are discussed. Management of infected or suspected medical staff is mentioned. The paper ends with guidelines concerning vaccination against COVID-19 in transplant recipients.

Carotid artery tortuosity may pose a problem during insertion of the tunneled catheter for hemodialysis.

Tortuosity of the carotid artery is usually an asymptomatic vascular abnormality and is discovered accidentally during cerebral angiography. These vascular changes may aggravate surgical procedures in the neck region. We described a technique of permanent catheter insertion in patients with renal graft failure in whom renal replacement therapy was necessary. Severe tortuosity of cervical arteries may make this procedure more difficult, necessitating a special technique, that is, full image monitoring.

Computed Tomography Parameters and Estimated Glomerular Filtration Rate Formulas for Peridonation Living Kidney Donor Assessment.

BACKGROUND: Renal function is usually described by the estimated glomerular filtration rate (eGFR). The standard method used for living kidney donor evaluation in our center is the 24-hour urine creatinine clearance (CrCl) and kidney morphology assessment with computed tomography (CT). The aim of the study was the analysis of the correlation of CrCl with 15 published eGFR formulas and morphologic CT parameters to choose the most accurate kidney function estimation method before and after donation. METHODS: The study included 39 living donors (18 male and 21 female, aged 32-69 years; mean age, 51.4 [SD, 9.7] years). The eGFR was estimated using Cockcroft-Gault, Modification of Diet in Renal Disease 7, Modification of Diet in Renal Disease 4, Chronic Kidney Disease Epidemiology Collaboration, Mayo Clinic, Nankivell, Bjornsson, Davis-Chandler, Edward-Whyte, Walser, Gates, Hull, Jelliffe-1, Jelliffe-2, or Mawer formulas and correlated with CrCl. CT parameters (kidney dimensions, volume, vascularization) were compared with eGFR formulas. RESULTS: The 25% to 34% (mean, 28.5% [SD, 2.3%]) decrease in eGFR after donation and its 1.5% to 5.0% (mean, 3.2% [SD, 1.0%]) increase over a year were observed. Cockcroft-Gault, Bjornsson, Hull, and Mawer equations (all including serum creatinine, age, sex, and body mass) correlated with predonation CrCl (r = 0.54, 0.53, 0.53, and 0.56, respectively; P < .001). From CT parameters, renal cortex volume correlated with CrCl (r = 0.48, P = .002) as well as the 4 abovementioned equations before donation (r = 0.65, 0.61, 0.64, and 0.74, respectively; P < .001) and during the postdonation period (12-month r = 0.59, 0.54, 0.57, and 0.70 respectively; P < .002). CONCLUSIONS: The eGFR calculated with equations combining serum creatinine, age, sex, and body mass as well as renal cortex volume are predictive of pre- and postdonation kidney function.

Conversion From a Twice-Daily to a Once-Daily Tacrolimus Formulation in Kidney Transplant Recipients.

BACKGROUND: The aim of the study was to assess bioavailability aspects of tacrolimus formulations during conversion from twice-daily (TAC BID) to once-daily (TAC OD) formulation in 89 stable kidney transplant recipients. MATERIALS AND METHODS: The study included 89 stable kidney transplant recipients transplanted between 1998 and 2008 (37 female, 52 male, aged 46.0 ± 12.4 years) and followed for 10 years. For a comprehensive comparison of the different tacrolimus formulations, dose-normalized trough levels (ng/mL/mg total daily dose, C/D ratio) and their variability were studied for 10 consecutive visits before and 6 months after conversion. RESULTS: The mean trough level decreased significantly 14 days after conversion (16%, 5.77 ± 1.94 [5.6, 4.5-6.5] ng/mL, P < .001). There was no significant difference between the tacrolimus trough levels before and 3 months after conversion (6.92 ± 1.89 [6.8, 5.9-8.0] ng/mL, P = .548). The tacrolimus daily dose 3 months after conversion (4.56 ± 1.81 [4.5, 3.5-5.5] mg/d) was significantly higher than the dose before conversion (4.16 ± 1.80 [4.0, 3.0-5.0] mg/d, P = .006). The post-conversion mean TAC trough level (10 measures) (6.6 [6.2-7.0] ng/mL) was similar to preconversion level (6.8 [5.6-7.9] ng/mL, P = .203). C/D ratio as well as C/D intrapatient variability (CV%) did not change during conversion (C/D 1.68 [1.36-2.53] vs 1.74 [1.41 vs 2.31], P = .075; CV% 19.5 [16.4-26.6] vs 24.4 [17.5-28.3], P = .114). CONCLUSIONS: Conversion from TAC BID to TAC OD is associated with a significant increase in tacrolimus dose during the first 3 months. In a long-term observation both formulations present similar dose-normalized trough levels and variability.

Post-transplant lymphoproliferative disorder in adult renal transplant recipients: case series and review of literature.

Post-transplant lymphoproliferative disorder (PTLD) is serious life-threating complication of transplantation. The clinical picture differs from lymphomas observed in the general population, with different manifestation, histopathology, higher aggressiveness with involvement of sites beyond the primary lymph node, and poorer outcome. The objective of the study was to present nine cases of PTLD observed in our centre among the kidney transplant recipient population and discuss the results with up-to-date literature. We performed a retrospective single-centre assessment of PTLD incidence in the cohorts of kidney transplant recipients followed by our centre. We found nine cases of PTLD, five men and four woman, aged from 26 to 67 years at the time of diagnosis (mean [SD] 48 [5] years), transplanted between 1997 and 2013. The disease was diagnosed between 2002 and 2017, from 6 to 440 months after transplantation (mean [SD] 96 [137] months). A diffuse large B-cell lymphoma was found in seven cases early as well as late after transplantation, and two patients presented T-cell lymphoma. Five patients achieved complete remission with no relapses after 6 to 13 months of treatment. In three cases the remission was achieved by switching to mammalian target of rapamycin inhibitors (mTORi) only. Four recipients died from 2 weeks to 15 months after PTLD was diagnosed. Although the diagnostic criteria of different forms of PTLD are commonly known, rapid and correct diagnosis is not easy. PTLD is a relatively a rare disease, so there are too few studies and little consensus on the optimal treatment.