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Introduction: Induction immunosuppression therapy plays a significant role in the prevention of acute rejection in renal transplantation. This study aimed to evaluate the effectiveness and safety of rabbit anti-thymocyte globulin (rATG) used as induction immunosuppression in Indian patients undergoing renal transplantation. Patients and Methods: RISE was a multicenter (n = 20), prospective observational cohort study of patients aged ≥ 18 years undergoing a first or repeat renal transplant and receiving rATG as part of the routine management practice. Twelve-month acute rejection was evaluated as a primary endpoint. Results: A total of 325 patients were enrolled, of which 313 patients received at least one dose of rATG with a mean (standard deviation [SD]) duration of induction therapy of 2.07 (1.33) days. The mean (SD) cumulative rATG induction dose was 2.6 (1.5) mg/kg. The mean (SD) glomerular filtration rate was 64.59 (19.57) mL/min/1.73 m2 at 6 months and 64.93 (20.26) mL/min/1.73 m2 at 1 year. The incidence of acute rejection at 1 year was 7.7% (n = 23). Graft rejection at 6 months was observed in 6.7% (n = 20) patients and an average time to first graft rejection of 5.4 and 10.3 months at 6 and 12 months, respectively. In total, 342 adverse events (AEs) were reported (n = 154, 49.2%) after 12 months, of which 11 events were related to the rATG treatment. Pyrexia was the most commonly reported serious adverse event (n = 10, 3.2%). Seven deaths were reported during the study. Conclusions: The study revealed the effectiveness and safety of rATG induction therapy in the Indian context as expected based on the data from randomized clinical trials. Trial Registration Number: CTRI/2017/09/009/009700.

Type IV pilus (TFP) is a multifunctional bacterial structure involved in twitching motility, adhesion, biofilm formation, as well as natural competence. Here, by site-directed mutagenesis and functional analysis, we determined the phenotype conferred by each of the 38 genes known to be required for TFP biosynthesis and regulation in the reemergent plant pathogenic fastidious prokaryote Xylella fastidiosa. This pathogen infects > 650 plant species and causes devastating diseases worldwide in olives, grapes, blueberries, and almonds, among others. This xylem-limited, insect-transmitted pathogen lives constantly under flow conditions and therefore is highly dependent on TFP for host colonization. In addition, TFP-mediated natural transformation is a process that impacts genomic diversity and environmental fitness. Phenotypic characterization of the mutants showed that ten genes were essential for both movement and natural competence. Interestingly, seven sets of paralogs exist, and mutations showed opposing phenotypes, indicating evolutionary neofunctionalization of subunits within TFP. The minor pilin FimT3 was the only protein exclusively required for natural competence. By combining approaches of molecular microbiology, structural biology, and biochemistry, we determined that the minor pilin FimT3 (but not the other two FimT paralogs) is the DNA receptor in TFP of X. fastidiosa and constitutes an example of neofunctionalization. FimT3 is conserved among X. fastidiosa strains and binds DNA non-specifically via an electropositive surface identified by homolog modeling. This protein surface includes two arginine residues that were exchanged with alanine and shown to be involved in DNA binding. Among plant pathogens, fimT3 was found in ~ 10% of the available genomes of the plant associated Xanthomonadaceae family, which are yet to be assessed for natural competence (besides X. fastidiosa). Overall, we highlight here the complex regulation of TFP in X. fastidiosa, providing a blueprint to understand TFP in other bacteria living under flow conditions.

The burden of hyperuricaemia has been steadily increasing both globally and in India. The increasing number of hyperuricaemia-associated co-morbidities, such as Chronic Kidney Disease (CKD), Type 2 Diabetes Mellitus (T2DM), Cardiovascular Diseases (CVD), and hypertension, implies that hyperuricaemia is associated with an increased risk of other chronic conditions or diseases. Despite the availability of several guidelines on hyperuricaemia, recommendations for appropriate titration of Urate Lowering Therapy (ULT) to achieve and maintain appropriate serum Uric Acid (sUA) levels in the Indian context are unclear. Another important challenge is the diagnosis and management of asymptomatic hyperuricaemia with ULT. This review summarises evidence-based discussion and review of literature by expert panellists on hyperuricaemia management with ULT, particularly with Xanthine Oxidase (XO) inhibitors. Based on the discussion, the experts developed a dose-titration algorithm for initiation and long-term management of hyperuricaemia with ULT, comprising febuxostat. The review also highlights some of the current challenges in hyperuricaemia management, which when addressed would benefit primary care physicians across the country for early screening and timely management of hyperuricaemia.

Older adults are at high risk of developing more severe consequences of substance use. Due to aging, they may also have multiple medical and psychiatric comorbidities as well as cognitive impairment. This may lead to forensic issues both in terms of civil and criminal matters. This article will review the forensic issues of substance use and their relevance to the older population in particular.

This study aimed to compare the outcomes of ABO-incompatible kidney transplantation (ABOiKT) with ABO-compatible kidney transplantation (ABOcKT) in a singlecenter study. A total of 30 consecutive ABOiKT recipients (ABOiKTR) from April 2014 to June 2015 were included in this study. All the patients received rituximab 200 mg/body for B-cell depletion. Plasmapheresis was done for anti-ABO antibody removal. The target anti-ABO titer was kept at

Abstract Background Xanthomonas citri, a causal agent of citrus canker, has been a well-studied model system due to recent availability of whole genome sequences of multiple strains from different geographical regions. Major limitations in our understanding of the evolution of pathogenicity factors in X. citri strains sequenced by short-read sequencing methods have been tracking plasmid reshuffling among strains due to inability to accurately assign reads to plasmids, and analyzing repeat regions among strains. X. citri harbors major pathogenicity determinants, including variable DNA-binding repeat region containing Transcription Activator-like Effectors (TALEs) on plasmids. The long-read sequencing method, PacBio, has allowed the ability to obtain complete and accurate sequences of TALEs in xanthomonads. We recently sequenced Xanthomonas citri str. Xc-03-1638-1-1, a copper tolerant A group strain isolated from grapefruit in 2003 from Argentina using PacBio RS II chemistry. We analyzed plasmid profiles, copy number and location of TALEs in complete genome sequences of X. citri strains. Results We utilized the power of long reads obtained by PacBio sequencing to enable assembly of a complete genome sequence of strain Xc-03-1638-1-1, including sequences of two plasmids, 249 kb (plasmid harboring copper resistance genes) and 99 kb (pathogenicity plasmid containing TALEs). The pathogenicity plasmid in this strain is a hybrid plasmid containing four TALEs. Due to the intriguing nature of this pathogenicity plasmid with Tn3-like transposon association, repetitive elements and multiple putative sites for origins of replication, we might expect alternative structures of this plasmid in nature, illustrating the strong adaptive potential of X. citri strains. Analysis of the pathogenicity plasmid among completely sequenced X. citri strains, coupled with Southern hybridization of the pathogenicity plasmids, revealed clues to rearrangements of plasmids and resulting reshuffling of TALEs among strains. Conclusions We demonstrate in this study the importance of long-read sequencing for obtaining intact sequences of TALEs and plasmids, as well as for identifying rearrangement events including plasmid reshuffling. Rearrangement events, such as the hybrid plasmid in this case, could be a frequent phenomenon in the evolution of X. citri strains, although so far it is undetected due to the inability to obtain complete plasmid sequences with short-read sequencing methods.

Plant growth-promoting rhizobacteria (PGPR) are increasingly used in crops worldwide. While selected PGPR strains can reproducibly promote plant growth under controlled greenhouse conditions, their efficacy in the field is often more variable. Our overall aim was to determine if pectin or orange peel (OP) amendments to Bacillus velezensis (Bv) PGPR strains could increase soybean growth and nodulation by Bradyrhizobium japonicum in greenhouse and field experiments to reduce variability. The treatments included untreated soybean seeds planted in field soil that contained Bv PGPR strains and non-inoculated controls with and without 0.1% (w/v) pectin or (1 or 10 mg/200 μL) orange peel (OP) amendment. In greenhouse and field tests, 35 and 55 days after planting (DAP), the plants were removed from pots, washed, and analyzed for treatment effects. In greenhouse trials, the rhizobial inoculant was not added with Bv strains and pectin or OP amendment, but in the field trial, a commercial B. japonicum inoculant was used with Bv strains and pectin amendment. In the greenhouse tests, soybean seeds inoculated with Bv AP193 and pectin had significantly increased soybean shoot length, dry weight, and nodulation by indigenous Bradyrhizobium compared to AP193 without pectin. In the field trial, pectin with Bv AP193 significantly increased the shoot length, dry weight, and nodulation of a commercial Bradyrhizobium japonicum compared to Bv AP193 without pectin. In greenhouse tests, OP amendment with AP193 at 10 mg significantly increased the dry weight of shoots and roots compared to AP193 without OP amendment. The results demonstrate that pectin-rich amendments can enhance Bv-mediated soybean growth promotion and nodulation by indigenous and inoculated B. japonicum.

Renal allograft rupture (RAR) is a rare but lethal complication of renal transplantation. It potentially threatens graft and patient survival. RAR is frequently associated with acute rejection, but other causes like renal vein thrombosis and acute tubular necrosis have also been observed. Most commonly a graft nephrectomy is required, but graft repair can also be attempted in selected cases to salvage the graft. Herein, we describe a rare case of spontaneous renal allograft rupture in the early posttransplant period due to acute tubular necrosis. A 42-year-old male, living donor renal allograft recipient, experienced RAR on the sixth posttransplant day. Surgical exploration showed two lacerations of 10 cm and 5 cm length at the upper and mid pole of the kidney. Histologically, the graft demonstrated acute tubular injury; no features of humoral or cellular rejection were identified. The successful management of this complication resulted in the salvage of the patient and the graft. This case demonstrates that early diagnosis and prompt treatment of a life-threatening RAR can salvage the graft.