Harnessing plant growth-promoting rhizobacteria, Bacillus subtilis and B. aryabhattai to combat salt stress in rice: a study on the regulation of antioxidant defense, ion homeostasis, and photosynthetic parameters.

Introduction: The ongoing global expansion of salt-affected land is a significant factor, limiting the growth and yield of crops, particularly rice (Oryza sativa L). This experiment explores the mitigation of salt-induced damage in rice (cv BRRI dhan100) following the application of plant growth-promoting rhizobacteria (PGPR). Methods: Rice seedlings, at five- and six-weeks post-transplanting, were subjected to salt stress treatments using 50 and 100 mM NaCl at seven-day intervals. Bacterial cultures consisting of endophytic PGPR (Bacillus subtilis and B. aryabhattai) and an epiphytic PGPR (B. aryabhattai) were administered at three critical stages: transplantation of 42-day-old seedlings, vegetative stage at five weeks post-transplantation, and panicle initiation stage at seven weeks post-transplantation. Results: Salt stress induced osmotic stress, ionic imbalances, and oxidative damage in rice plants, with consequent negative effects on growth, decrease in photosynthetic efficiency, and changes in hormonal regulation, along with increased methylglyoxal (MG) toxicity. PGPR treatment alleviated salinity effects by improving plant antioxidant defenses, restoring ionic equilibrium, enhancing water balance, increasing nutrient uptake, improving photosynthetic attributes, bolstering hormone synthesis, and enhancing MG detoxification. Discussion: These findings highlight the potential of PGPR to bolster physiological and biochemical functionality in rice by serving as an effective buffer against salt stress-induced damage. B. subtilis showed the greatest benefits, while both the endophytic and epiphytic B. aryabhattai had commendable effects in mitigating salt stress-induced damage in rice plants.

An Effective Combination Therapy for the Treatment of Pediatric Monomorphic Post-transplant Lymphoproliferative Disorder With Plasmacytic Differentiation.

Post-transplant lymphoproliferative disorder (PTLD) is a complication of immunosuppressive therapy following solid organ or hematopoietic cell transplantation. Initial treatment typically includes a reduction of immunosuppression with or without rituximab. However, the optimal therapy for PTLD with plasmacytic differentiation is unclear. We present 3 cases of pediatric patients with plasmacytic PTLD. Two patients received a standard rituximab-based approach and relapsed, prompting additional chemotherapy. The third patient was treated with a novel regimen of bortezomib, dexamethasone, and daratumumab. This regimen was safe, well-tolerated, and resulted in a 2-year remission. Larger studies are needed to further explore this regimen.

Letermovir as Cytomegalovirus Prophylaxis in a Pediatric Cohort: A Retrospective Analysis.

Letermovir is an attractive cytomegalovirus (CMV) prophylactic agent, but published data in children are scarce. This retrospective chart review aimed to describe our experience using letermovir as CMV prophylaxis in pediatric hematopoietic cell transplantation (HCT) recipients. Pediatric patients (age <20 years) undergoing allogeneic HCT and receiving letermovir prophylaxis in the Mayo Clinic Pediatric Bone Marrow Transplant Program were eligible for inclusion in this retrospective chart review. Medical records were reviewed to evaluate letermovir dosing, CMV levels, laboratory values, and reports of adverse effects. Between October 2020 and April 2022, 9 patients age 4 to 19 years undergoing allogeneic HCT in the Pediatric Bone Marrow Transplant Program received letermovir prophylaxis, either 240 mg or 480 mg daily at a mean and median dose of 10 mg/kg/day. Letermovir was crushed and administered via nasogastric tube in 4 of 9 patients. Two patients received letermovir for secondary CMV prophylaxis after initial treatment with ganciclovir/valganciclovir, and the remaining 7 received letermovir for primary prophylaxis. One patient, a 20-kg 6-year-old female receiving 240 mg (12 mg/kg), experienced low-level CMV viremia while on letermovir. No other patients experienced CMV reactivation while on letermovir prophylaxis. In 2 patients, transient mild transaminitis was noted within the first weeks of letermovir therapy, which resolved without intervention, and its relationship to letermovir could not be clearly established. Letermovir administration was feasible and well tolerated as CMV prophylaxis in our small cohort of pediatric patients undergoing HCT. Larger, prospective studies are warranted to confirm the safety and efficacy of letermovir in children. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Improving Timely Antibiotic Administration for Pediatric Oncology Patients With Neutropenic Fever Seen in the Emergency Department.

Objective: To improve the care for pediatric oncology patients with neutropenic fever who present to the emergency department (ED) by administering appropriate empiric antibiotics within 60 minutes of arrival. Patients and Methods: We focused on improving the care for pediatric oncology patients at risk of neutropenia who presented to the ED with concern for fever. Our baseline adherence to the administration of empiric antibiotics within 60 minutes for this population was 53% (76/144) from January 1, 2010, to December 21, 2014. During 2015, we reviewed data monthly, finding 73% adherence. We used the Lean methodology to identify the process waste, completed a value-stream map with input from multidisciplinary stakeholders, and convened a root cause analysis to identify causes for delay. The 4 causes were as follows: (1) lack of staff awareness; (2) missing patient information in electronic medical record; (3) practice variation; and 4) lack of clear prioritization of laboratory draws. We initiated Plan-Do-Study-Act cycles to achieve our goal of 80% of patients receiving appropriate empiric antibiotics within 60 minutes of arrival in the ED. Results: Five Plan-Do-Study-Act cycles were completed, focusing on the following: (1) timely identification of patients by utilizing the electronic medical record to initiate a page to the care team; (2) creation of a streamlined intravascular access process; (3) practice standardization; (4) convenient access to appropriate antibiotics; and (5) care team education. Timely antibiotic administration increased from 73%-95% of patients by 2018. More importantly, the adherence was sustained to greater than 90% through 2021. Conclusion: A structured and multifaceted approach using quality improvement methodologies can achieve and sustain improved patient care outcomes in the ED.

Spectrum of hematological malignancies, clonal evolution and outcomes in 144 Mayo Clinic patients with germline predisposition syndromes.

Germline predisposition syndromes (GPS) result from constitutional aberrations in tumor suppressive and homeostatic genes, increasing risk for neoplasia in affected kindred. In this study, we present clinical and genomic data on 144 Mayo Clinic patients with GPS; 59 evaluated prospectively using an algorithm-based diagnostic approach in the setting of a dedicated GPS/ inherited bone marrow failure syndrome (IBMFS) clinic. Seventy-two (50%) patients had IBMFS (telomere biology disorders-32,Fanconi anemia-18, Diamond Blackfan Anemia - 11, congenital neutropenia-5, Schwachman-Diamond Syndrome-5 and Bloom Syndrome-1), 27 (19%) had GPS with antecedent thrombocytopenia (RUNX1-FPD-15, ANKRD26-6, ETV6-2, GATA1-1, MPL-3), 28 (19%) had GPS without antecedent thrombocytopenia (GATA2 haploinsufficiency-16, DDX41-10, CBL-1 and CEBPA-1) and 17 (12%) had general cancer predisposition syndromes (ataxia telangiectasia-7, heterozygous ATM variants-3, CHEK2-2, TP53-2, CDK2NA-1, NF1-1 and Nijmegen Breakage Syndrome-1). Homozygous and heterozygous ATM pathogenic variants were exclusively associated with lymphoproliferative disorders (LPD), while DDX41 GPS was associated with LPD and myeloid neoplasms. The use of somatic NGS-testing identified clonal evolution in GPS patients, with ASXL1, RAS pathway genes, SRSF2 and TET2 being most frequently mutated. Fifty-two (91%) of 59 prospectively identified GPS patients had a change in their management approach, including additional GPS-related screening in 42 (71%), referral for allogenic HSCT workup and screening of related donors in 16 (27%), medication initiation and selection of specific conditioning regimens in 14 (24%), and genetic counseling with specific intent of fertility preservation and preconceptual counseling in 10 (17%) patients; highlighting the importance of dedicated GPS screening, detection and management programs for patients with hematological neoplasms.

Complete genome and plasmid sequence of a novel Bacillus sp. BD59S, a parasporal protein synthesizing bacterium.

Parasporal crystalline inclusion proteins of some Bacillus spp. are of paramount importance due to their insecticidal, nematocidal, and cancer cell killing capabilities. Here, we present a brief report of the complete genome sequence of Bacillus sp. BD59S, a bacterium that produced HeLa cell-killing parasporal crystalline inclusion proteins. From genome sequencing and assembly, we found that the bacterium has one circular chromosome and two large plasmids, pBTBD59S1 and pBTBD59S2. The size of the chromosome is 5283,933 bp with a 35.4% GC content, consisting of 5938 genes and 5550 protein-coding sequences (CDSs), 25 complete rRNAs (5S, 16S, 23S), 98 tRNAs, 5 ncRNAs, 260 pseudo-genes, and 356 subsystems. Complete plasmid sequence of pBTBD59S1 comprises a total size of 162,149 bp with 33.4% GC content, 192 CDSs, and 13 subsystems. The other plasmid pBTBD59S2, is 199,209 bp long with 32.9% GC content, 179 CDSs, and 11 subsystems. Analyses by NCBI microbial genome BLAST, phylogenetic genome tree, and BLAST ring image generator (BRIG) revealed that BD59S belongs to Bacillus cereus group, and is more close to B. thuringiensis. Further, the strain possesses 57.04 kDa and 54.42 kDa Cry protein-coding genes, which show significant similarities with cancer cell-killing parasporin proteins of B. thuringiensis strains.

Understanding the evolving phenotype of vascular complications in telomere biology disorders.

Vascular complications such as bleeding due to gastrointestinal telangiectatic anomalies, pulmonary arteriovenous malformations, hepatopulmonary syndrome, and retinal vessel abnormalities are being reported in patients with telomere biology disorders (TBDs) more frequently than previously described. The international clinical care consortium of telomere-associated ailments and family support group Dyskeratosis Congenita Outreach, Inc. held a workshop on vascular abnormalities in the TBDs at the National Cancer Institute in October 2017. Clinicians and basic scientists reviewed current data on vascular complications, hypotheses for the underlying biology and developed new collaborations to address the etiology and clinical management of vascular complications in TBDs.

Clinical Correlates and Treatment Outcomes for Patients With Short Telomere Syndromes.

Short telomere syndromes (STSs) are accelerated aging syndromes with multisystemic manifestations that present complex management challenges. In this article, we discuss a single-institution experience in diagnosing and managing patients with inherited STSs. In total, we identified 17 patients with short telomeres, defined by flow-fluorescence in-situ hybridization telomere lengths of less than first centile in granulocytes/lymphocytes OR the presence of a characteristic germline pathogenic variant in the context of a highly suggestive clinical phenotype. Genetic variations in the telomere complex were identified in 6 (35%) patients, with 4 being known pathogenic variants involving TERT (n=2), TERC (n=1), and DKC1 (n=1) genes, while 2 were variants of uncertain significance in TERT and RTEL1 genes. Idiopathic interstitial pneumonia (IIP) (n=12 [71%]), unexplained cytopenias (n=5 [29%]), and cirrhosis (n=2 [12%]) were most frequent clinical phenotypes at diagnosis. At median follow-up of 48 (range, 0-316) months, Kaplan-Meier estimate of overall survival, median (95% CI), was 182 (113, not reached) months. Treatment modalities included lung transplantation for IIP (n=5 [29%]), with 3 patients developing signs of acute cellular rejection (2, grade A2; 1, grade A1); danazol therapy for cytopenias (n=4 [24%]), with only 1 out of 4 patients showing a partial hematologic response; and allogeneic hematopoietic stem cell transplant for progressive bone marrow failure (n=2), with 1 patient dying from transplant-related complications. In summary, patients with STSs present with diverse clinical manifestations and require a multidisciplinary approach to management, with organ-specific transplantation capable of providing clinical benefit.

Complete Genome Sequence of Bacillus subtilis Strain MH1, Which Has a High Level of Bacteriocin-Like Activity, Isolated from Soil in Bangladesh.

Bacillus subtilis MH1 demonstrates a high level of bacteriocin activity against several pathogenic bacteria. We announce here the full-genome sequence of strain MH1, isolated from soil in Bangladesh. This genome length is 4,094,053 bp, with 43.5% GC content, 4,217 coding sequences (CDS), 10 rRNA, 84 tRNA, and 1 transfer-messenger RNA (tmRNA).

Hepatosplenic γδ T-cell lymphoma of two adolescents: Case report and retrospective literature review in children, adolescents, and young adults.

HSTCL is a highly aggressive malignancy with a poor prognosis. Case series and accounts have reported the use of different chemotherapy regimens with diverse patient outcomes. Most long-term survivors had undergone high-dose chemotherapy with autologous or allogeneic HCT. We describe two pediatric patients with HSTCL who were treated with chemotherapy followed by allogeneic HCT. Both patients are alive and in complete remission 2 and 8 years after therapy. Multiagent chemotherapy followed with allogeneic HCT seems to provide patients who have chemotherapy-sensitive disease a long-term disease-free survival.

Thrombotic and hemorrhagic complications in children and young adult recipients of Hematopoietic Stem Cell Transplant (HSCT).

BACKGROUND: Overall incidence of hemostatic complications in pediatric recipients of Hematopoietic Stem Cell Transplant (HSCT) is scarcely studied. This retrospective review explored the incidence and underlying risk factors of bleeding and thrombotic complications in children. PROCEDURE: Clinical characteristics, hemorrhagic events (HE), thrombotic events (TE) and follow up data were abstracted from medical records on patients aged <21 years undergoing HSCT during January 2000-June 2015. RESULTS: From start of conditioning until last follow up, 238 pediatric patients were reviewed during this study. There were 16 symptomatic thrombotic complications in 15 patients, along with 13 major bleeding events. Incidence of HE or TE was higher in allogeneic HSCT compared to autologous HSCT (p = 0.02). Severe thrombocytopenia could not be identified as a major contributor to bleeding. All patients with HE had platelets between 20,000-50,000 × 109/L, except one patient, who had platelets <20,000 × 109/L. All patients with hemorrhagic cystitis (n = 7) had received cyclophosphamide (Cy). For patients with sinusoidal obstruction syndrome, conditioning included either busulfan (Bu)/Cy (n = 5), Cy with total body irradiation (n = 4), or thiotepa (n = 2). Among allogeneic HSCT recipients, 60% of HE and 92% with TE had underlying myeloid neoplasms. Graft versus Host disease contributed to both types of complications (p = 0.07), although not reaching statistical significance. CONCLUSIONS: Allogeneic pediatric HSCT patients had higher overall risk of hemorrhagic or thrombotic complications compared to autologous recipients in this study. HSCT for myeloid malignancies was a risk factor for higher complications.