Employing Bacillus and Pseudomonas for phytonematode management in agricultural crops.

Phytonematodes are responsible for causing significant harm and reducing yields in various agricultural crops. To minimize losses caused by phytonematodes and meet the high demand for agricultural production, it is important to develop effective strategies with minimal environmental impact to manage this biotic stress. Due to the adverse environmental effects associated with synthetic pesticides, it is imperative to use beneficial bacteria, such as Bacillus and Pseudomonas spp., for biocontrol purposes to control phytonematode infestation in agricultural settings. This approach has gained considerable attraction, as there is a promising market for eco-friendly biopesticides based on bacteria that can effectively manage phytonematodes. Furthermore, biocontrol strains of Bacillus and Pseudomonas have the potential to enhance crop productivity by producing various substances that promote plant growth and development. This review aims to explore the role of Bacillus and Pseudomonas spp. in phytonematode management, elucidate different mechanisms by which these bacteria suppress nematode populations, and discuss the future prospects of utilizing these bacteria in agriculture.

A Prospective Study of Incidence, Risk Factors, and Outcomes of Acute Kidney Injury in Coronavirus Disease 2019.

Background: Acute kidney injury (AKI) is common after coronavirus 2 infection (COVID-19), leading to higher morbidity and mortality. There is little prospective data from India regarding the incidence, risk factors, and outcome of AKI in COVID-19. Materials and Methods: This study was conducted prospectively in adult patients between September and December 2020 in a tertiary care hospital in the national capital region of Delhi. A total of 856 patients with COVID-19 infection were enrolled in the study. Survivors were followed for 3 months after discharge. Results: Out of 856 patients, 207 (24%) developed AKI. AKI was significantly higher in those with severe disease as compared to mild-moderate disease (88% vs. 12%, P = 0.04). Out of all AKI, 3.4% had stage 1, 9.2% had stage 2, and the rest 87.4% had stage 3 AKI. 183/207 (88%) patients were on mechanical ventilators, 133 (64%) required inotropic support, and 137/207 (83.6%) patients required kidney replacement therapy. Out of 207 AKI patients, 74% (153) died as compared to 4% (27) in non-AKI group (P = 0.0001). After 3 months, chronic kidney disease (CKD) developed in 10/54 (18.5%) patients. On multivariable analysis, the presence of diabetes mellitus, severe COVID-19 disease, high levels of C reactive protein, lactate dehydrogenase, D-Dimer, and use of intravenous steroids, tocilizumab and remdesivir, were found to be significant predictors of AKI. Conclusion: AKI is common after COVID-19 infection and it is a significant risk factor for mortality in COVID-19. Patients with diabetes and high levels of inflammatory markers have higher mortality. CKD may develop in many patients after discharge.

Genome-wide identification of nuclear factor -Y (NF-Y) transcription factor family in finger millet reveals structural and functional diversity.

The Nuclear Factor Y (NF-Y) is one of the widely explored transcription factors (TFs) family for its potential role in regulating molecular mechanisms related to stress response and developmental processes. Finger millet (Eleusine coracana (L.) Gaertn) is a hardy and stress-tolerant crop where partial efforts have been made to characterize a few transcription factors. However, the NF-Y TF is still poorly explored and not well documented. The present study aims to identify and characterize NF-Y genes of finger millet using a bioinformatics approach. Genome mining revealed 57 EcNF-Y (Eleusine coracana Nuclear Factor-Y) genes in finger millet, comprising 18 NF-YA, 23 NF-YB, and 16 NF-YC genes. The gene organization, conserved motif, cis-regulatory elements, miRNA target sites, and three-dimensional structures of these NF-Ys were analyzed. The nucleotide substitution rate and gene duplication analysis showed the presence of 7 EcNF-YA, 10 EcNF-YB, and 8 EcNF-YC paralogous genes and revealed the possibilities of synonymous substitution and stabilizing selection during evolution. The role of NF-Ys of finger millet in abiotic stress tolerance was evident by the presence of relevant cis-elements such as ABRE (abscisic acid-responsive elements), DRE (dehydration-responsive element), MYB (myeloblastosis) or MYC (myelocytomatosis). Twenty-three isoforms of miR169, mainly targeting a single NF-Y gene, i.e., the EcNF-YA13 gene, were observed. This interaction could be targeted for finger millet improvement against Magnaporthe oryzae (blast fungus). Therefore, by this study, the putative functions related to biotic and abiotic stress tolerance for many of the EcNF-Y genes could be explored in finger millet.

Cardiac Migration of Chemoport Catheter-A Rare Complication: Review of Literature and Our Experience.

Chemoport devices are commonly used for the administration of chemotherapeutic medication in cancer patients and can also be used for total parenteral nutrition and long term intravenous therapy. They are usually inserted through the internal jugular vein or the subclavian vein. The common complications of the procedure include pneumothorax, bleeding, arrhythmia and venous thrombosis. One of the rare complications of chemoport is catheter fracture/dislodgement and subsequent migration, with an incidence of 0.1-2.1%. Other rare complications are vascular erosion and embolization, vocal cord palsy and mediastinal hematoma. The aims and objectives are as follows: (1) to report a rare case of chemoport catheter migration between the right ventricle and pulmonary artery and (2) to review the literature on the rare complication of cardiac migration of a chemoport. A 56-year-old lady, known case of carcinoma right breast, post modified radical mastectomy was advised adjuvant chemotherapy. A chemoport catheter was placed in the right internal jugular vein and was positioned over the left upper chest. The 1st cycle of chemotherapy was given through chemoport and was uneventful. On the second chemotherapy schedule, catheter dysfunction was found. For the same, she was evaluated with chest radiography, which showed the migrated catheter in the heart. The migrated catheter was retrieved by snare technique using percutaneous transvenous route. The procedure was uneventful. The literature on the topic was reviewed. Chemoport catheter fracture or dislodgement and its subsequent cardiac migration are a rare but serious complication. High index of suspicion in case of catheter dysfunction, early detection by chest radiography, and timely multi-disciplinary intervention is crucial.

Role of Induction in a Haplomatch, Related, Low-Risk, Living-Donor Kidney Transplantation with Triple Drug Immunosuppression: A Single-Center Study.

Background: The role of induction in low-risk, living-donor kidney transplants being treated with tacrolimus, mycophenolate mofetil, and prednisolone is debatable. Materials and Methods: This was a retrospective study that consisted of patients undergoing living kidney transplantation between February 2010 and June 2021 with a related haplomatch donor, with maintenance immunosuppression of tacrolimus, mycophenolate mofetil, and prednisolone. High-risk transplants, such as second or more transplants, immunologically incompatible transplants, and steroid-free transplants, were excluded. Patients were divided into three groups: no induction, basiliximab induction, and thymoglobulin induction, and the outcomes of all three were compared. Results: A total of 350 transplants were performed. There was a significant difference in the recipient sex distribution (P = 0.0373) and the number of preemptive transplants (P = 0.0272) between the groups. Other parameters were comparable. Biopsy-proven acute rejection (BPAR) was significantly less frequent in the thymoglobulin group than in the no-induction (5.3% vs. 17.5%; P = 0.0051) or basiliximab (5.3% vs. 18.8%; P = 0.0054) group. This persisted even after we performed multivariate regression analysis (thymoglobulin vs. no-induction group, P = 0.0146; thymoglobulin vs. basiliximab group, P = 0.0237). There was no difference in BPAR between the basiliximab and no-induction groups. There were no differences in other outcomes between the groups. Conclusion: In a low-risk haplomatch, related, living-donor kidney transplant on tacrolimus, mycophenolate mofetil, and prednisolone, BPAR was significantly lower with thymoglobulin as opposed to no induction or basiliximab induction with a similar short-term patient and death-censored graft survival and infection rates. Basiliximab did not provide any benefit over no induction.

Multi-targeted therapeutic exploration of Tamarix gallica flowers for anti-ulcer activity and associated complications.

BACKGROUND: Peptic ulcer is a condition characterized by open sores resulting from excessive acid production in the stomach or digestive tract, causing damage to the mucosal lining. Tamarix gallica (TG), is traditionally known for its anti-inflammatory, antioxidant, antibacterial activity, etc. Objective: The scientific evidences based on its efficacy specifically for anti-ulcers activity are limited, hence, the study aimed to evaluate protective effect of TG against aspirin-induced peptic ulcers. MATERIALS AND METHODS: Phytochemical screening was performed followed by assessment of protective effect of TG against aspirin induced toxicity in rats. Network biology and polypharmacology studies were performed to determine the possible molecular targets involved in pathophysiology of ulcers. RESULTS: The study revealed that the TG extract at high dose (500 mg/kg b.w.) significantly exhibits protective effect against aspirin induced ulcers via regulation of free acidity pepsin production, overall acidity via regulating antioxidant status (SOD, GSH, CAT, etc). Morphological studies revealed less damage with less disruption of the gastric mucosa layer having normal mucosal structure, no swelling or oedema was found in drug treated groups. CONCLUSION: Moreover, network biology and polypharmacology outcomes revealed that SOD2, CAT, EPO, IL10, EGF, TGFB1 etc. play a significant role in functional gastrointestinal-associated disease or peptic ulcer. Hence, the study concludes that TG polyphenols including phenols and flavonoids play an important role in alleviation of peptic ulcer or associated complication and thus demonstrating TG as a natural therapeutic regimen against ulcers in glance of nature.

Prognosis of MGMT -Positive Gene in Patients with Brain Tumors of Grade III and Grade IV.

Sumit GoyalObjective To evaluate MGMT gene positivity is associated with better survival in patients diagnosed with brain tumor World Health Organization (WHO) grades III and IV Material and Methods Single-institute restrospective study. A total of 80 patients were enrolled, all underwent surgery either total or subtotal excision of the tumor and MGMT gene testing on tumor tissue by RT-PCR. All received adjuvant radiation (60 Gy/30 fractions, 5 fractions/week) with concurrent temozolomide (75 mg/m 2 ), followed by 12 cycles of adjuvant temozolomide (150 mg/m 2 1st cycle followed by 200 mg/m 2 ) with regular follow-up. Results A total of 80 patients, 75 underwent subtotal excision, 27 were WHO grade III vs. 48 WHO grade IV. Five underwent total excision 1 was WHO grade III vs. 4 WHO grade IV. The median PFS and OS in five patients in total excision in grade III patient was 9.0 and 20 compared with Grade IV, where the median PFS and OS was 8.8 and 17.8 months. Out of 75 patients in the subtotal group median PFS and OS, respectively, in Grade III group was 9.1 and 19.3 and, WHO grade IV with median PFS of 8.8 and OS of 18.8. Conclusion MGMT gene positivity is a prognostic factor in grade III and IV brain tumor.

Development of a major histocompatibility complex class II conditional knockout mouse to study cell-specific and time-dependent adaptive immune responses in peripheral nerves.

INTRODUCTION/AIMS: The precise relationship between molecular mimicry and tissue-specific autoimmunity is unknown. Major histocompatibility complex (MHC) class II antigen presenting cell-CD4+ T-cell receptor complex interactions are necessary for adaptive immunity. This study aimed to determine the role of endoneurial endothelial cell MHC class II in autoimmune polyneuropathy. METHODS: Cryopreserved Guillain-Barré syndrome (GBS) patient sural nerve biopsies and sciatic nerves from the severe murine experimental autoimmune neuritis (sm-EAN) GBS model were studied. Cultured conditional ready MHC Class II antigen A-alpha chain (H2-Aa) embryonic stem cells were used to generate H2-Aaflox/+ C57BL/6 mice. Mice were backcrossed and intercrossed to the SJL background to generate H2-Aaflox/flox SJL mice, bred with hemizygous Tamoxifen-inducible von Willebrand factor Cre recombinase (vWF-iCre/+) SJL mice to generate H2-Aaflox/flox; vWF-iCre/+ mice to study microvascular endothelial cell adaptive immune responses. Sm-EAN was induced in Tamoxifen-treated H2-Aaflox/flox; vWF-iCre/+, H2-Aaflox/flox; +/+, H2-Aa+/+; vWF-iCre/+ and untreated H2-Aaflox/flox; vWF-iCre/+ adult female SJL mice. Neurobehavioral, electrophysiological and histopathological assessments were performed at predefined time points. RESULTS: Endoneurial endothelial cell MHC class II expression was observed in normal and inflamed human and mouse peripheral nerves. Tamoxifen-treated H2-Aaflox/flox; vWF-iCre/+ mice were resistant to sm-EAN despite extensive MHC class II expression in lymphoid and non-lymphoid tissues. DISCUSSION: A conditional MHC class II knockout mouse to study cell- and time-dependent adaptive immune responses in vivo was developed. Initial studies show microvascular endothelial cell MHC class II expression is necessary for peripheral nerve specific autoimmunity, as advocated by human in vitro adaptive immunity and ex vivo transplant rejection studies.

Proteome-wide analysis reveals G protein-coupled receptor-like proteins in rice (Oryza sativa).

G protein-coupled receptors (GPCRs) constitute the largest family of transmembrane proteins in metazoans that mediate the regulation of various physiological responses to discrete ligands through heterotrimeric G protein subunits. The existence of GPCRs in plant is contentious, but their comparable crucial role in various signaling pathways necessitates the identification of novel remote GPCR-like proteins that essentially interact with the plant G protein α subunit and facilitate the transduction of various stimuli. In this study, we identified three putative GPCR-like proteins (OsGPCRLPs) (LOC_Os06g09930.1, LOC_Os04g36630.1, and LOC_Os01g54784.1) in the rice proteome using a stringent bioinformatics workflow. The identified OsGPCRLPs exhibited a canonical GPCR 'type I' 7TM topology, patterns, and biologically significant sites for membrane anchorage and desensitization. Cluster-based interactome mapping revealed that the identified proteins interact with the G protein α subunit which is a characteristic feature of GPCRs. Computational results showing the interaction of identified GPCR-like proteins with G protein α subunit and its further validation by the membrane yeast-two-hybrid assay strongly suggest the presence of GPCR-like 7TM proteins in the rice proteome. The absence of a regulator of G protein signaling (RGS) box in the C- terminal domain, and the presence of signature motifs of canonical GPCR in the identified OsGPCRLPs strongly suggest that the rice proteome contains GPCR-like proteins that might be involved in signal transduction.

Recycling of printed Xerographic paper using Aspergillus assiutensis enzyme cocktail: an integrated approach to sustainable development.

To overcome the human and animal survivability risk, sustainable development is the only option on earth that can be achieved through the maximum use of renewable environmental resources. Recycling of waste paper is an emerging waste management approach to conserve natural resources. Herein, we studied enzyme-mediated process to recycle the xerographic paper by using the crude fungal extract from indigenously isolated fungi identified as Aspergillus assiutensis. The fungal enzyme cocktail has been characterized for the production of multiple enzymes namely cellulase, amylase, xylanase, pectinase, and protease. All these enzymes have pH optima in the acidic range and except cellulase and all the enzymes are stable from 10 to 80 C. In the zymogram analysis, pectinase, xylanase, amylase, and cellulase were detected at 68 kDa, ~ 54 kDa, 38 kDa, and 30 kDa, respectively. Also, the presence of protease was confirmed by the clear zone at 68, 31, and 16 kDa. A 26% decrease in the kappa number and reduction in Hex A of the pulp was observed on the treatment of the pulp with enzyme as compared to the control pulp without any treatment. The physical and chemical properties of the pulp were also improved by enzyme-mediated pulping as compared to the control The physiochemical parameter of the effluent like TDS was reduced (397 ppm) significantly in comparison to chemical deinking process and it was within the permissible limit. BOD and alkalinity were reduced when the enzymes and chemical dosage were used in combination. These results indicate that chemi-enzymatic deinking is most promising to reduce or remove the pollution parameters including ink and this approach can be used in the paper and pulp industry for sustainable development.

Synthesis, antifungal evaluation, two-dimensional quantitative structure-activity relationship and molecular docking studies of isoxazole derivatives as potential fungicides.

BACKGROUND: Sheath blight and bakanae disease, prominent among emerging rice ailments, exert a profound impact on rice productivity, causing severe impediments to crop yield. Excessive use of older fungicides may lead to the development of resistance in the pathogen. Indeed, a pressing and immediate need exists for novel, low-toxicity and highly selective fungicides that can effectively combat resistant fungal strains. RESULTS: A series of 20 isoxazole derivatives were synthesized using alkoxy/halo acetophenones and N,N-dimethylformamidedimethylacetal. These compounds were characterized by various spectroscopic techniques, namely 1H nuclear magnetic resonance (NMR), 13C NMR and liquid chromatography-high-resolution mass spectrometry, and were evaluated for their fungicidal activity against Rhizoctonia solani and Fusarium fujikuroi. Compound 5n (5-(2-chlorophenyl) isoxazole) exhibited highest activity (effective dose for 50% inhibition [ED50] = 4.43 µg mL-1) against R. solani, while 5p (5-(2,4-dichloro-2-hydroxylphenyl) isoxazole) exhibited highest activity (ED50 = 6.7 µg mL-1) against F. fujikuroi. Two-dimensional quantitative structural-activity relationship (QSAR) analysis, particularly multiple linear regression (MLR) (Model 1), highlighted chi6chain and DistTopo as the key descriptors influencing fungicidal activity. Molecular docking studies revealed the potential of these isoxazole derivatives as novel fungicides targeting sterol 14α-demethylase enzyme, suggesting their importance as crucial intermediates for the development of novel and effective fungicides. CONCLUSION: All test compounds were effective in inhibiting both fungi, according to the QSAR model, with various descriptors, such as structural, molecular shape analysis, electronic and thermodynamic, playing an important role. Molecular docking studies confirmed that these compounds can potentially replace commercially available fungicides and help control fungal pathogens in rice crops effectively. © 2024 Society of Chemical Industry.

Weight gain in infants with congenital heart disease; breastfeeding alone versus supplemental spoon-feeding of expressed breast milk: an open-label, pilot, randomised control trial.

OBJECTIVES: Infants with congenital heart disease and increased pulmonary blood flow frequently suffer from feeding difficulties and growth failure. Providing expressed breast milk by spoon has been hypothesised to decrease energy expenditure in these infants as compared to breastfeeding. This study assessed the effect of supplemental feeding of expressed breast milk on weight gain in infants with unoperated congenital heart disease. METHOD: This was a prospective open-label randomised control trial. In total, 50 infants with post tricuspid left to right shunt were enrolled in the study. In the intervention group, apart from breastfeeding, a minimum predetermined volume of expressed breast milk was targeted to be given by spoon. 30-50 kcal/kg/day was given by expressed breast milk by spoon-feeding. In the control group, the infants were given at least 8 feeds per 24 hours by direct breastfeeding. Both groups were followed up for 1 month and assessed for weight gain. RESULT: Despite a high rate of protocol breach in both groups (30% overall), infants in the intervention group had better weight gain at one-month follow-up compared to those in the control group, 780 ± 300 versus 530 ± 250 gm (p = 0.01). CONCLUSION: In infants with left to right shunts, supplemental feeding of expressed breast milk by spoon along with breastfeeding resulted in significantly higher average weight gain at 30 days compared to the control group who received breastfeeding alone. Future studies with larger sample sizes and longer follow-ups need to be done to confirm the findings of this study.

Expression profiling of Nuclear Factor-Y (NF-Y) transcription factors during dehydration and salt stress in finger millet reveals potential candidate genes for multiple stress tolerance.

MAIN CONCLUSION: Expression profiling of NF-Y transcription factors during dehydration and salt stress in finger millet genotypes contrastingly differing in tolerance levels identifies candidate genes for further characterization and functional studies. The Nuclear Factor-Y (NF-Y) transcription factors are known for imparting abiotic stress tolerance in different plant species. However, there is no information on the role of this transcription factor family in naturally drought-tolerant crop finger millet (Eleusine coracana L.). Therefore, interpretation of expression profiles against drought and salinity stress may provide valuable insights into specific and/or overlapping expression patterns of Eleusine coracana Nuclear Factor-Y (EcNF-Y) genes. Given this, we identified 59 NF-Y (18 NF-YA, 23 NF-YB, and 18 NF-YC) encoding genes and designated them EcNF-Y genes. Expression profiling of these genes was performed in two finger millet genotypes, PES400 (dehydration and salt stress tolerant) and VR708 (dehydration and salt stress sensitive), subjected to PEG-induced dehydration and salt (NaCl) stresses at different time intervals (0, 6, and 12 h). The qRT-PCR expression analysis reveals that the six EcNF-Y genes namely EcNF-YA1, EcNF-YA5, EcNF-YA16, EcNF-YB6, EcNF-YB10, and EcNF-YC2 might be associated with tolerance to both dehydration and salinity stress in early stress condition (6 h), suggesting the involvement of these genes in multiple stress responses in tolerant genotype. In contrast, the transcript abundance of finger millet EcNF-YA5 genes was also observed in the sensitive genotype VR708 under late stress conditions (12 h) of both dehydration and salinity stress. Therefore, the EcNF-YA5 gene might be important for adaptation to salinity and dehydration stress in sensitive finger millet genotypes. Therefore, this gene could be considered as a susceptibility determinant, which can be edited to impart tolerance. The phylogenetic analyses revealed that finger millet NF-Y genes share strong evolutionary and functional relationship to NF-Ys governing response to abiotic stresses in rice, sorghum, maize, and wheat. This is the first report of expression profiling of EcNF-Ys genes identified from the finger millet genome and reveals potential candidate for enhancing dehydration and salt tolerance.

Zirconium oxide nano-catalyzed synthesis of pharmacologically important bis(indolyl)methanes: a highly efficient and mild approach.

We report herein a highly efficient and mild approach for synthesizing pharmacologically active bis(indolyl)methanes 3a-z, utilizing ZrO2 nanoparticles as a catalyst. The method involves a condensation reaction between indole and diverse aromatic aldehydes in acetonitrile under mild conditions. The ZrO2 nano-catalyst prepared via a co-precipitation method demonstrates exceptional efficacy, leading to favourable yields of the target bis(indolyl)methanes 3a-z. The versatility of this methodology is highlighted through substrate screening, showcasing its applicability to various aromatic aldehydes.

Phenotypic and genetic characterization of unexplored, potential cattle population of Madhya Pradesh.

Bawri or Garri, a non-descript cattle population managed under an extensive system in Madhya Pradesh state of India, was identified and characterized both genetically and phenotypically to check whether or not it can be recognised as a breed. The cattle have white and gray colour and are medium sized with 122.5 ± 7.5 cm and 109.45 ± 0.39 cm height at withers in male and female, respectively. Double-digest restriction site associated DNA (ddRAD) sequencing was employed to identify ascertainment bias free SNPs representing the entire genome cost effectively; resulting in calling 1,156,650 high quality SNPs. Observed homozygosity was 0.76, indicating Bawri as a quite unique population. However, the inbreeding coefficient was 0.025, indicating lack of selection. SNPs found here can be used in GWAS and genetic evaluation programs. Considering the uniqueness of Bawri cattle, it can be registered as a breed for its better genetic management.

Litsea glutinosa extract promotes fracture healing and prevents bone loss via BMP2/SMAD1 signaling.

Estrogen deficiency is one of the main causes for postmenopausal osteoporosis. Current osteoporotic therapies are of high cost and associated with serious side effects. So there is an urgent need for cost-effective anti-osteoporotic agents. Anti-osteoporotic activity of Litsea glutinosa extract (LGE) is less explored. Moreover, its role in fracture healing and mechanism of action is still unknown. In the present study we explore the osteoprotective potential of LGE in osteoblast cells and fractured and ovariectomized (Ovx) mice models. Alkaline phosphatase (ALP), MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and mineralization assays revealed that LGE treatment increased osteoblast cell differentiation, viability and mineralization. LGE treatment at 0.01 µg increased the expression of BMP2, PSMAD, RUNX2 and type 1 col. LGE also mitigated RANKL-induced osteoclastogenesis. Next, drill hole injury Balb/C mice model was treated with LGE for 12 days. Micro-CT analysis and Calcein labeling at the fracture site showed that LGE (20 mg/kg) enhanced new bone formation and bone regeneration, also increased expression of BMP2/SMAD1 signaling genes at fracture site. Ovx mice were treated with LGE for 1 month. µCT analysis indicated that the treatment of LGE at 20 mg/kg dose prevented the alteration in bone microarchitecture and maintained bone mineral density and bone mineral content. Treatment also increased bone strength and restored the bone turnover markers. Furthermore, in bone samples, LGE increased osteogenesis by enhancing the expression of BMP2/SMAD1 signaling components and decreased osteoclast number and surface. We conclude that LGE promotes osteogenesis via modulating the BMP2/SMAD1 signaling pathway. The study advocates the therapeutic potential of LGE in osteoporosis treatment.

Prevention of dialysis disequilibrium syndrome in children with advanced uremia with a structured hemodialysis protocol: A quality improvement initiative study.

BACKGROUND: Dialysis disequilibrium syndrome (DDS) is a rare but significant concern in adult and pediatric patients undergoing dialysis initiation with advanced uremia or if done after an interval. It is imperative to gain insights into the epidemiological patterns, pathophysiological mechanisms, and preventive strategies aimed at averting the onset of this ailment. DESIGN: Prospective observational quality improvement initiative cohort study. SETTING AND PARTICIPANTS: A prospective single-center study involving 50 pediatric patients under 18 years recently diagnosed with chronic kidney disease stage V with blood urea ≥200 mg/dL, admitted to our tertiary care center for dialysis initiation from January 2017 to October 2023. QUALITY IMPROVEMENT PLAN: A standardized protocol was developed and followed for hemodialysis in pediatric patients with advanced uremia. This protocol included measures such as lower urea reduction ratios (targeted at 20%-30%) with shorter dialysis sessions and linear dialysate sodium profiling. Prophylactic administration of mannitol and 25% dextrose was also done to prevent the incidence of dialysis disequilibrium syndrome. MEASURES: Incidence of dialysis disequilibrium syndrome and severe dialysis disequilibrium syndrome, mortality, urea reduction ratios (URRs), neurological outcome at discharge, and development of complications such as infection and hypotension. Long-term outcomes were assessed at the 1-year follow-up including adherence to dialysis, renal transplantation, death, and loss to follow-up. RESULTS: The median serum creatinine and urea levels at presentation were 7.93 and 224 mg/dL, respectively. A total of 20% of patients had neurological symptoms attributable to advanced uremia at the time of presentation. The incidence of dialysis disequilibrium syndrome was 4% (n = 2) with severe dialysis disequilibrium syndrome only 2% (n = 1). Overall mortality was 8% (n = 4) but none of the deaths were attributed to dialysis disequilibrium syndrome. The mean urea reduction ratios for the first, second, and third dialysis sessions were 23.45%, 34.56%, and 33.50%, respectively. The patients with dialysis disequilibrium syndrome were discharged with normal neurological status. Long-term outcomes showed 88% adherence to dialysis and 38% renal transplantation. LIMITATIONS: This study is characterized by a single-center design, nonrandomized approach, and limited sample size. CONCLUSIONS: Our structured protocol served as a framework for standardizing procedures contributing to low incidence rates of dialysis disequilibrium syndrome.

A novel inducible von Willebrand Factor Cre recombinase mouse strain to study microvascular endothelial cell-specific biological processes in vivo.

Mouse models are invaluable to understanding fundamental mechanisms in vascular biology during development, in health and different disease states. Several constitutive or inducible models that selectively knockout or knock in genes in vascular endothelial cells exist; however, functional and phenotypic differences exist between microvascular and macrovascular endothelial cells in different organs. In order to study microvascular endothelial cell-specific biological processes, we developed a Tamoxifen-inducible von Willebrand Factor (vWF) Cre recombinase mouse in the SJL background. The transgene consists of the human vWF promoter with the microvascular endothelial cell-selective 734 base pair sequence to drive Cre recombinase fused to a mutant estrogen ligand-binding domain [ERT2] that requires Tamoxifen for activity (CreERT2) followed by a polyadenylation (polyA) signal. We initially observed Tamoxifen-inducible restricted bone marrow megakaryocyte and sciatic nerve microvascular endothelial cell Cre recombinase expression in offspring of a mixed strain hemizygous C57BL/6-SJL founder mouse bred with mT/mG mice, with >90% bone marrow megakaryocyte expression efficiency. Founder mouse offspring were backcrossed to the SJL background by speed congenics, and intercrossed for >10 generations to develop hemizygous Tamoxifen-inducible vWF Cre recombinase (vWF-iCre/+) SJL mice with stable transgene insertion in chromosome 1. Microvascular endothelial cell-specific Cre recombinase expression occurred in the sciatic nerves, brains, spleens, kidneys and gastrocnemius muscles of adult vWF-iCre/+ SJL mice bred with Ai14 mice, with retained low level bone marrow and splenic megakaryocyte expression. This novel mouse strain would support hypothesis-driven mechanistic studies to decipher the role(s) of specific genes transcribed by microvascular endothelial cells during development, as well as in physiologic and pathophysiologic states in an organ- and time-dependent manner.