Omnipresence of Partitiviruses in Rice Aggregate Sheath Spot Symptom-Associated Fungal Isolates from Paddies in Thailand

Partitiviruses are one of the most prevalent double-stranded RNA viruses that have been identified mostly in filamentous fungi and plants. Partitiviruses generally infect host fungi asymptomatically but infrequently exert significant effect(s) on morphology and virulence, thus being considered a potential source of biological control agents against pathogenic fungi. In this study, we performed a screening for mycoviruses of a collection of Thai isolates of rice fungal pathogen Rhizoctonia oryzae-sativae, a causal agent of rice aggregated sheath spot disease. As a result, 36% of tested isolates carried potentially viral double-stranded RNAs with sizes ranging from 2 to 3 kbp. By conventional cDNA library construction and RNA-seq, we determined six new alphapartitiviruses that infected three isolates: tentatively named Rhizoctonia oryzae-sativae partitivirus 1 to 6 (RosPV1-6). Furthermore, RT-PCR detection of each virus revealed their omnipresent nature in different R. oryzae-sativae isolates. Although virus-curing of basidiomycetous fungi is generally difficult, our repeated attempts successfully obtained virus-free (for RosPV1, RosPV2, and uncharacterized partitiviruses), isogenic strain of R. oryzae-sativae TSS190442. The virus-cured strain showed slightly faster colony growth on the synthetic media and severe symptom development on the rice sheath compared to its virus-infected counterpart. Overall, this study shed light on the distribution of partitiviruses in R. oryzae-sativae in a paddy environment and exemplified a virus-curing protocol that may be applicable for other basidiomycetous fungi.     

Erythropoietin and its non‐erythropoietic derivative: Do they ameliorate renal tubulointerstitial injury in ureteral obstruction?

Objectives: Pleiotropic effects of recombinant human erythropoietin (EPO) have recently been discovered in many non‐renal animal models. The renoprotective effects of EPO and carbamylated‐erythropoietin (CEPO), a novel EPO which has a small stimulatory effect on hemoglobin, have never been explored in unilateral ureteral obstruction (UUO), a chronic tubulointerstitial (TI) disease model which is independent of systemic factors. Methods: In order to examine the effects of EPO and CEPO treatments on renal TI injury, 36 male Sprague‐Dawley rats, weighing 250–320 g, underwent: UUO without treatment (group 1, n = 12), UUO with EPO (groups 2, n = 12), and UUO with CEPO (group 3, n = 12). EPO and CEPO were injected subcutaneously at a dose of 5000 u/kg to each respective rat at 1 day pre‐UUO and at day 3, 7 and 10 post‐UUO. After days 3, 7, and 14 of UUO, TI injury, collagen, α‐smooth muscle actin (α‐SMA) positive cell, ED1‐positive cell, terminal deoxynucleotidyl transferase (TdT) mediated nick‐end labeling (TUNEL)‐positive cell, and transforming growth factor‐β1 (TGF‐β1) messenger ribonucleic acid (mRNA) were determined. Bcl‐2 expression was also assessed to verify the mechanism of apoptosis. Results: At day 14 UUO caused severe TI injury with a significant increase in collagen, α‐SMA, ED1‐positive cell, TUNEL‐positive cell, and TGF‐β1 mRNA expression. Administration of EPO and CEPO significantly attenuated TI injury, collagen, ED1‐positive cells, and TUNEL‐positive cells. Only CEPO‐treated rats had decreased α‐SMA positive cells and TGF‐β1 mRNA. The expression of Bcl‐2 was demonstrated only in EPO‐treated rats. The hematocrit levels in EPO‐treated rats were higher than the control and CEPO‐treated rats. Conclusions: EPO and CEPO can limit 14‐day UUO‐induced TI injury by reducing inflammation, interstitial fibrosis, and tubular apoptosis.     

Biosimilar recombinant human erythropoietin induces the production of neutralizing antibodies

Recombinant human erythropoietin (r-HuEpo) has been used for the treatment of renal anemia. With the loss of its patent protection, there has been an upsurge of more affordable biosimilar agents, increasing patient access to treatment for these conditions. The complexity of the manufacturing process for these recombinant proteins, however, can result in altered properties that may significantly affect patient safety. As it is not known whether various r-HuEpo products can be safely interchanged, we studied 30 patients with chronic kidney disease treated by subcutaneous injection with biosimilar r-HuEpo and who developed a sudden loss of efficacy. Sera from 23 of these patients were positive for r-HuEpo-neutralizing antibodies, and their bone marrow biopsies indicated pure red-cell aplasia, indicating the loss of erythroblasts. Sera and bone marrow biopsies from the remaining seven patients were negative for anti-r-HuEpo antibodies and red-cell aplasia, respectively. The cause for r-HuEpo hyporesponsiveness was occult gastrointestinal bleeding. Thus, subcutaneous injection of biosimilar r-HuEpo can cause adverse immunological effects. A large, long-term, pharmacovigilance study is necessary to monitor and ensure patient safety for these agents.     

Severe hyponatremia as the presenting manifestation of primary empty sella syndrome

Severe hyponatremia is associated with neurological impairment and mortality. Furthermore, severe hyponatremia can be the first presentation of several diseases. Therefore, an appropriate investigation for the underlying causes of hyponatremia apart from the proper correction of sodium levels, might lead to a diagnosis of occult diseases.     

Metabolic effects of kidney donation: A Bayesian analysis of matched cohorts

The kidney is a notable site of glycolysis, gluconeogenesis, and fatty acid oxidation. Loss of a kidney after kidney donation might, therefore, affect the glucose and lipid metabolism of the donors. This matched cohort study investigated the effect of nephrectomy on glucose and lipid metabolisms using Bayesian hypothesis testing. There were 77 pairs of matched donor-control pairs in the present study. Clinical and laboratory data of the participants, at baseline and 1-year, were extracted from electronic medical records. Comparisons between donor and control groups were performed using the Bayesian independent samples t-test or Bayesian Mann–Whitney test. The Bayes Factor for alternative hypothesis over null hypothesis (BF₁₀) was used to compare the two competing hypotheses. The BF₁₀ of 3 or more was considered evidence for the alternative hypothesis. Comparing changes from baseline to 1-year between donors and controls, the BF₁₀ of triglycerides, high-density lipoprotein cholesterol (HDL-C), triglyceride-glucose (TyG) index of insulin resistance, and estimated glomerular filtration rate (eGFR) were 7.95, 3.96, 30.13, and 1.32 x 10⁴¹, respectively signifying that the change of these variables in the donors differed from those in the controls (alternative hypothesis). Triglyceride, HDL-C, and TyG index of the donors increased more than those of the controls while eGFR of the donor decreased more than that of the controls. Our data suggest that triglycerides and insulin resistance increase after donor nephrectomy. Kidney donors should be informed about these metabolic changes and should adhere to lifestyle recommendations that may mitigate insulin resistance.