Translation and Pilot Validation of Hindi, Marathi, and Bangla Translation of Quality-of-Life EORTC Radiation Proctitis Module (PRT-20) for Routine Clinical Use.

Rahul Krishnatry The aim of this study was to translate and validate the European Organization for Research and Treatment for Cancer (EORTC) "Radiation Proctitis" (PRT-20) module in Hindi, Marathi, and Bangla languages. The EORTC PRT-20 was translated into Hindi, Marathi, and Bangla using EORTC guidelines. Two separate translators first translated the original questionnaire into the three regional languages, following which a reconciled forward translation was compiled. This reconciled version in each language was then back-translated into English by two other translators. This back-translated version was then compared with the original the EORTC questionnaire for correctness, and the preliminary questionnaires were formed in all three languages. The EORTC translation unit approved the questionnaires. The preliminary questionnaires were administered to 30 patients (10 for each language) diagnosed with rectal or anal canal cancer who had received pelvic radiotherapy and were at risk of developing PRT. None of the patients had seen the questionnaire before. After filling out the questionnaire, each patient was interviewed for difficulty in answering, confusion, understanding, or if any of the questions were upsetting and if patients would have asked the question differently. No changes were suggested for Marathi and Bangla translations. Two modifications were suggested in the Hindi translation, which was then retested in five patients and finalized. All the suggestions were incorporated into the preliminary questionnaires, which were sent back to the EORTC for final approval. After reviewing the entire report of pilot testing for the translated quality-of-life questionaire-PRT-20 in three languages, it was approved by the EORTC translation unit. The translated questionnaires were reliable, with Cronbach α values of 0.767, 0.799, and 0.898 for Hindi, Marathi, and Bangla, respectively. The Hindi, Marathi, and Bangla translations of PRT-20 have been approved by the EORTC and can be used in routine clinical practice.

High Rates of Placental Inflammation Among Samples Collected by the MOMI Consortium.

BACKGROUND: The Multi-Omics for Mothers and Infants (MOMI) consortium aims to improve birth outcomes. Preterm birth is a major obstetric complication globally causing significant infant and childhood morbidity and mortality. OBJECTIVES: We analyzed placental samples (basal plate, placenta/chorionic villi and/or the chorionic plate) collected by the 5 MOMI sites: The Alliance for Maternal and Newborn Health Improvement (AMANHI) Bangladesh, AMANHI Pakistan, AMANHI Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) Bangladesh and GAPPS Zambia. The goal was to analyze the morphology and gene expression of samples collected from preterm and uncomplicated term births. STUDY DESIGN: The teams provided biopsies from 166 singleton preterm (<37 weeks) and 175 term (≥37 weeks) deliveries. They were formalin-fixed and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphological analyses. Other placental biopsies (n = 35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics. RESULTS: The morphological analyses revealed a surprisingly high rate of inflammation involving the basal plate, placenta/chorionic villi and/or the chorionic plate. The rate in chorionic villus samples, likely attributable to chronic villitis, ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs. the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes as differentially expressed (DE) between placentas from preterm vs. term births (123 upregulated, 144 downregulated). Mapping the DE genes onto single cell RNA-seq data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathological findings, GO (Gene Ontology) analyses highlighted leukocyte infiltration/activation and inflammatory responses in both the fetal and maternal compartments. CONCLUSION: The relationship between placental inflammation and preterm birth is appreciated in developed countries. Here, we show that this link also exists in developing geographies. Also, among the participating sites, we found geographic- and/or population-based differences in placental inflammation and preterm birth, suggesting the importance of local factors.

Development of a nano-emulsion based multivalent protein subunit vaccine against Pseudomonas aeruginosa.

Pseudomonas aeruginosa (Pa) is an opportunistic bacterial pathogen responsible for severe hospital acquired infections in immunocompromised and elderly individuals. Emergence of increasingly drug resistant strains and the absence of a broad-spectrum prophylactic vaccine against both T3SA+ (type III secretion apparatus) and ExlA+/T3SA- Pa strains worsen the situation in a post-pandemic world. Thus, we formulated a candidate subunit vaccine (called ExlA/L-PaF/BECC/ME) against both Pa types. This bivalent vaccine was generated by combining the C-terminal active moiety of exolysin A (ExlA) produced by non-T3SA Pa strains with our T3SA-based vaccine platform, L-PaF, in an oil-in-water emulsion. The ExlA/L-PaF in ME (MedImmune emulsion) was then mixed with BECC438b, an engineered lipid A analogue and a TLR4 agonist. This formulation was administered intranasally (IN) to young and elderly mice to determine its potency across a diverse age-range. The elderly mice were used to mimic the infection seen in elderly humans, who are more susceptible to serious Pa disease compared to their young adult counterparts. After Pa infection, mice immunized with ExlA/L-PaF/BECC/ME displayed a T cell-mediated adaptive response while PBS-vaccinated mice experienced a rapid onset inflammatory response. Important genes and pathways were observed, which give rise to an anti-Pa immune response. Thus, this vaccine has the potential to protect aged individuals in our population from serious Pa infection.

Shigella Vaccines: The Continuing Unmet Challenge.

Shigellosis is a severe gastrointestinal disease that annually affects approximately 270 million individuals globally. It has particularly high morbidity and mortality in low-income regions; however, it is not confined to these regions and occurs in high-income nations when conditions allow. The ill effects of shigellosis are at their highest in children ages 2 to 5, with survivors often exhibiting impaired growth due to infection-induced malnutrition. The escalating threat of antibiotic resistance further amplifies shigellosis as a serious public health concern. This review explores Shigella pathology, with a primary focus on the status of Shigella vaccine candidates. These candidates include killed whole-cells, live attenuated organisms, LPS-based, and subunit vaccines. The strengths and weaknesses of each vaccination strategy are considered. The discussion includes potential Shigella immunogens, such as LPS, conserved T3SS proteins, outer membrane proteins, diverse animal models used in Shigella vaccine research, and innovative vaccine development approaches. Additionally, this review addresses ongoing challenges that necessitate action toward advancing effective Shigella prevention and control measures.

Optimization of the Form Factors of Advanced Li-S Pouch Cells.

Lithium-sulfur (Li-S) batteries hold immense promise as next-generation energy storage due to their high theoretical energy density (2600 Wh kg⁻¹), low cost, and non-toxic nature. However, practical implementation faces challenges, primarily from Li polysulfide (LiPS) shuttling within the cathode and Li dendrite growth at the anode. Optimized electrodes/electrolytes design effectively confines LiPS to the cathode, boosting cycling performance in coin cells to up to hundreds of cycles. Scaling up to larger pouch cells presents new obstacles, requiring further research for long-term stability. A 1.45 Ah pouch cell, with optimized sulfur loading and electrolyte/sulfur ratio is developed, which delivers an energy density of 151 Wh kg-1 with 70% capacity retention up to 100 cycles. Targeting higher energy density (180 Wh kg-1 ), the developed 1Ah pouch cell exhibits 68% capacity retention after 50 cycles. Morphological analysis reveals that pouch cell failure is primarily from Li metal powdering and resulting polarization, rather than LiPS shuttling. This occurs for continuous Li ion stripping/plating during cycling, leading to dendrite growth and formation of non-reactive Li powder, especially under high currents. These issues increase ion diffusion resistance and reduce coulombic efficiency over time. Therefore, the study highlights the importance of a protected Li metal anode for achieving high-energy-dense batteries.

Assessment of the Practices and Perspectives of Healthcare Providers Towards Utilization of Telemedicine for the Care of Adult Patients With Diabetes Mellitus During the COVID-19 Pandemic in India.

Background and purpose The lockdowns and restrictions enforced periodically during the COVID-19 pandemic posed a serious challenge for non-COVID care, especially in diabetes where telediabetes, the utilization of telemedicine consultations for diabetic care, became more necessary than ever before. Although studies have shed light on the perception of patients, there is a paucity of studies from the perspective of healthcare providers, especially in an Indian context. Moving forward, it is imperative to understand the perspectives of telediabetes providers in this domain. Hence, a nationwide survey was carried out to assess providers' practices and perspectives towards using telemedicine for providing diabetes care in India during the COVID-19 pandemic and beyond. Methods An online questionnaire-based, cross-sectional study was carried out involving diabetes care physicians. The study tool was developed after the identification of broad themes and constructs from published literature, national guidelines, and diabetes experts' recommendations, following which, it was validated by six experts and pilot-tested. An online open survey, hosted on a professional platform, was circulated to internists, endocrinologists, and other diabetes care physicians of various institutions, hospitals, and clinics from both public and private sectors across the country through individual and group emails and various mobile messenger services. Results Out of the 239 doctors who responded to the survey, 195 (81.6%) had provided telediabetes services since the COVID-19 outbreak, and 84.1% were actively providing teleconsultations for diabetes at the time of the survey. The majority of participants (63.2%) were private practitioners. Telediabetes engagement was 3.5 hours per day at the peak of the pandemic and reduced significantly to one hour after the end of the pandemic. Video calling was the most preferred modality for consultation, whereas messaging services were preferred for input from the patients. Printed prescription images followed by text messages were the common modalities for sending treatment advice. The overall perception towards telediabetes was positive (50.1%). Most physicians reported being reasonably and somewhat aware (65.6% and 20.5%, respectively) of telemedicine practice guidelines but were not sure about the extent of compliance. Conclusions Our study sheds light not only on the utilization of telediabetes from physicians' perspectives and practices but also on its acceptability while identifying areas requiring clarity and focus moving forward.

Translation and pilot validation of Hindi, Marathi, and Bangla translation of quality of life EORTC module (QLQ-SH-22) for assessing sexual health-related quality of life.

AIM: To translate and validate the European Organization for Research and Treatment for Cancer (EORTC) module for assessing the sexual health-related quality of life in cancer patients (QLQ-SH22), in Hindi, Marathi, and Bangla languages for clinical use. METHODS AND RESULTS: The EORTC QLQ-SH-22 was translated into Hindi, Marathi, and Bangla by adopting standard guidelines given by EORTC. Initially, the original questionnaire was forward translated by two separate translators, followed by the reconciliation of the forward translations by a third person. This was followed by two back translations of the reconciled version into English by two other translators. These back-translated questions were then compared with the original EORTC questions for accuracy, and once acceptable, a preliminary questionnaire was prepared in all three languages. These questionnaires were then pilot tested with 30 patients (10 for each language) diagnosed with any of the cancers in the pelvic region who are expected to be at risk of sexual quality of life due to tumor or treatment like pelvic radiotherapy. Participated patients had never seen or filled the questionnaire before, each patient was interviewed after filling the questionnaire for difficulty in answering, confusion, difficulty understanding, or if any of the questions were upsetting and if patients would have asked the question differently. RESULTS: None of the patients reported any changes or suggestions for all the three translations. All the translated questionnaires were well understood by all the patients. Pilot testing reports were sent to EORTC. After reviewing the entire report of Hindi, Marathi, and Bangla translations, these questionnaires were approved by the EORTC translation unit. The questionnaires are reliable with Cronbach's α for Hindi, Marathi, and Bangla being 0.69, 0.66, and 0.86, respectively. CONCLUSION: The final Hindi, Marathi, and Bangla translations of SH 22 have been approved by the EORTC and can be used to assess the sexual health of cancer patients in routine oncology practices and/or clinical studies.

Early to mid-pregnancy HbA1c levels and its association with adverse pregnancy outcomes in three low middle-income countries in Asia and Sub-Saharan Africa.

BACKGROUND: Hyperglycemia during pregnancy leads to adverse maternal and fetal outcomes. Thus, strict monitoring of blood glucose levels is warranted. This study aims to determine the association of early to mid-pregnancy HbA1c levels with the development of pregnancy complications in women from three countries in South Asia and Sub-Saharan Africa. METHODS: We performed a secondary analysis of the AMANHI (Alliance for Maternal and Newborn Health Improvement) cohort, which enrolled 10,001 pregnant women between May 2014 and June 2018 across Sylhet-Bangladesh, Karachi-Pakistan, and Pemba Island-Tanzania. HbA1c assays were performed at enrollment (8 to < 20 gestational weeks), and epidemiological data were collected during 2-3 monthly household visits. The women were followed-up till the postpartum period to determine the pregnancy outcomes. Multivariable logistic regression models assessed the association between elevated HbA1c levels and adverse events while controlling for potential confounders. RESULTS: A total of 9,510 pregnant women were included in the analysis. The mean HbA1c level at enrollment was found to be the highest in Bangladesh (5.31 ± 0.37), followed by Tanzania (5.22 ± 0.49) and then Pakistan (5.07 ± 0.58). We report 339 stillbirths and 9,039 live births. Among the live births were 892 preterm births, 892 deliveries via cesarean section, and 532 LGA babies. In the multivariate pooled analysis, maternal HbA1c levels of ≥ 6.5 were associated with increased risks of stillbirths (aRR = 6.3, 95% CI = 3.4,11.6); preterm births (aRR = 3.5, 95% CI = 1.8-6.7); and Large for Gestational Age (aRR = 5.5, 95% CI = 2.9-10.6). CONCLUSION: Maternal HbA1c level is an independent risk factor for predicting adverse pregnancy outcomes such as stillbirth, preterm birth, and LGA among women in South Asia and Sub-Saharan Africa. These groups may benefit from early interventional strategies.

Preoperative Wire Localization: A Simple Guidance Technique for Excision of Deep, Painful, Small, Soft Tissue Neurofibromas.

A novel use of preoperative wire localization to aid in the removal of small deep-seated soft tissue nerve sheath tumors is described. Wire localization is commonly used in breast surgery, and applying this technique in neurosurgery will enable the surgeon to directly reach the lesion with smaller incisions and prevent unnecessary soft tissue dissection.

The L-DBF vaccine cross protects mice against different Shigella serotypes after prior exposure to the pathogen.

IMPORTANCE: Shigellosis is endemic to low- and middle-income regions of the world where children are especially vulnerable. In many cases, there are pre-existing antibodies in the local population and the effect of prior exposure should be considered in the development and testing of vaccines against Shigella infection. Our study shows that L-DBF-induced immune responses are not adversely affected by prior exposure to this pathogen. Moreover, somewhat different cytokine profiles were observed in the lungs of vaccinated mice not having been exposed to Shigella, suggesting that the immune responses elicited by Shigella infection and L-DBF vaccination follow different pathways.

Impact of the TLR4 agonist BECC438 on a novel vaccine formulation against Shigella spp.

Shigellosis (bacillary dysentery) is a severe gastrointestinal infection with a global incidence of 90 million cases annually. Despite the severity of this disease, there is currently no licensed vaccine against shigellosis. Shigella's primary virulence factor is its type III secretion system (T3SS), which is a specialized nanomachine used to manipulate host cells. A fusion of T3SS injectisome needle tip protein IpaD and translocator protein IpaB, termed DBF, when admixed with the mucosal adjuvant double-mutant labile toxin (dmLT) from enterotoxigenic E. coli was protective using a murine pulmonary model. To facilitate the production of this platform, a recombinant protein that consisted of LTA-1, the active moiety of dmLT, and DBF were genetically fused, resulting in L-DBF, which showed improved protection against Shigella challenge. To extrapolate this protection from mice to humans, we modified the formulation to provide for a multivalent presentation with the addition of an adjuvant approved for use in human vaccines. Here, we show that L-DBF formulated (admix) with a newly developed TLR4 agonist called BECC438 (a detoxified lipid A analog identified as Bacterial Enzymatic Combinatorial Chemistry candidate #438), formulated as an oil-in-water emulsion, has a very high protective efficacy at low antigen doses against lethal Shigella challenge in our mouse model. Optimal protection was observed when this formulation was introduced at a mucosal site (intranasally). When the formulation was then evaluated for the immune response it elicits, protection appeared to correlate with high IFN-γ and IL-17 secretion from mucosal site lymphocytes.

Improved pearl millet genomes representing the global heterotic pool offer a framework for molecular breeding applications.

High-quality reference genome assemblies, representative of global heterotic patterns, offer an ideal platform to accurately characterize and utilize genetic variation in the primary gene pool of hybrid crops. Here we report three platinum grade de-novo, near gap-free, chromosome-level reference genome assemblies from the active breeding germplasm in pearl millet with a high degree of contiguity, completeness, and accuracy. An improved Tift genome (Tift23D2B1-P1-P5) assembly has a contig N50 ~ 7,000-fold (126 Mb) compared to the previous version and better alignment in centromeric regions. Comparative genome analyses of these three lines clearly demonstrate a high level of collinearity and multiple structural variations, including inversions greater than 1 Mb. Differential genes in improved Tift genome are enriched for serine O-acetyltransferase and glycerol-3-phosphate metabolic process which play an important role in improving the nutritional quality of seed protein and disease resistance in plants, respectively. Multiple marker-trait associations are identified for a range of agronomic traits, including grain yield through genome-wide association study. Improved genome assemblies and marker resources developed in this study provide a comprehensive framework/platform for future applications such as marker-assisted selection of mono/oligogenic traits as well as whole-genome prediction and haplotype-based breeding of complex traits.

Role of preoperative anterior segment optical coherence tomography in identifying intraoperative posterior capsular dehiscence in posterior polar cataract.

INTRODUCTION: The presence of preoperative posterior capsular dehiscence in posterior polar cataracts (PPCs) increases the chances of intraoperative posterior capsular rent. Our study aims to demonstrate the efficacy of preoperative anterior segment optical coherence tomography (ASOCT) to predict intraoperative posterior capsular rupture (PCR) in PPC. MATERIALS AND METHODS: This was an observational study including patients within 25-75 years of age, having PPC, undergoing phacoemulsification. ASOCT was done for evaluating preoperative posterior capsular status and was graded as "intact" or "dehiscent, and eventually ,intraoperative-posterior capsular status was noted. STATISTICAL ANALYSIS: SPSS (version 27.0) was used, and P value of ≤ 0.05 was considered statistically significant. RESULTS: ASOCT of 44 eyes had 9 (20.5%) dehiscent posterior capsules and 35 (79.5%) intact. Out of these 9 eyes, 7 (77.8%) had intraoperative PCR and 2 (22.2%) did not. Out of these 35, 34 (97.1%) were actually intact intraoperatively and 1 (2.9%) had intraoperative PCR. The sensitivity and specificity of ASOCT for detecting dehiscence were 94.4% and 87.5%, respectively. The positive and negative predictive values were 97.1 and 77.8, respectively. The diagnostic accuracy of the test was 95.45% with a Chi-square value of 27.01 (P < 0.0001). The diagnostic validity of ASOCT grading for detecting preoperative dehiscence was confirmed. The association between intraoperative PCR and preoperative dehiscence was statistically significant (Chi-square test - P < 0.0001). Our objective was established. DISCUSSION AND CONCLUSION: The demographics and clinical parameters were comparable with other studies. Two eyes with preoperative dehiscence on ASOCT had intact posterior capsule during surgery. The cause can be a dense opacity with increased optical density causing an obscured a clear capsule view on ASOCT, an artifact defect, giving a false impression of dehiscence. One eye who had nondehiscent PC on ASOCT was found to have PCR on the table, which can be due to an extremely thin PC or tightly adherent polar opacity to the capsule. According to our study, the diagnostic accuracy of ASOCT for detecting preoperative dehiscence was 94.4% (sensitivity)and of nondehiscence was 87.5%(specificity). 97.1% of eyes with dehiscence on ASOCT, had actual posterior capsular rent (positive predictive value). To conclude, ASOCT can be used as a reliable diagnostic modality.

A MXene-BiFeO3-ZnO nanocomposite photocatalyst served as a high-performance supercapacitor electrode.

MXenes have attracted considerable attention in the field of energy storage and conversion due to their high surface area, excellent electrical conductivity, and ability to intercalate various ions. However, simultaneously achieving high capacitance, rate capability, cycling stability, and mechanical flexibility is a significant challenge for designing MXene-based supercapacitors. In this article, we explored MXene-BiFeO3-ZnO nanocomposites for both photocatalytic and electric double-layer supercapacitor applications. While the BiFeO3-ZnO nanohybrid heterostructure improves the charge separation properties in nanocomposite photocatalysts, it was applied as an interlayer spacer between the MXene layers to prevent the stacking effect of electrodes in the supercapacitor. Furthermore, the optimization of MXene content in the nanocomposite was established by photocatalytic studies on methylene blue dye, which revealed a maximum of 98.72% degradation under direct sunlight with superior stability. The electrochemical studies on the best composition material reveal a maximum areal capacitance (Ccv) of 142.8 mF cm-2, an energy density (E) of 1.65 µW h cm-2, and a capacitive retention of 99.98% after 8000 cycles at 7 µA cm-2. Additionally, the flexible solid-state supercapacitor fabricated with the same material demonstrates an areal capacitance of 47.6 mF cm-2 and a capacitive retention of 66% after 8000 cycles at 7 µA cm-2, with potential for high-performance flexible supercapacitors.

Modifying skin flaps for achieving very large decompressive craniectomies in malignant middle cerebral artery territory infarcts: A technical note.

INTRODUCTION: Decompressive craniectomy is a well described treatment to salvage life in large middle cerebral artery (MCA) territory infarcts. The size of the craniectomy is limited by the size of the skin incision and very large craniectomies need large skin flaps that are prone to necrosis at the wound margins. MATERIAL AND METHODS: We describe two modifications in the skin flap that we have used in 7 patients to achieve very large bony decompressions in malignant MCA infarctions without compromising on flap vascularity. One consists of a linear extension posteriorly from the question mark or reverse question mark incision while the other is an "n" shaped incision. RESULTS: With these modifications we achieved craniectomies of size 15.6-17.8 cm in the anteroposterior and 10.7-12 cm in vertical axis of the bone flap removed in our patients. There were no additional procedural or wound related complications in a 6-month follow up. CONCLUSIONS: Removal of a standard size bone flap may achieve suboptimal decompression in cases of large MCA territory infarctions. Imaginative tailoring of skin flaps helps to remove larger volumes of skull with no added procedural morbidity.

Physicochemical characterization of biological and synthetic forms of two lipid A-based TLR4 agonists.

Toll-like receptor (TLR) agonists are recognized as potential immune-enhancing adjuvants and are included in several licensed vaccines. Monophosphoryl lipid A (MPL®, GlaxoSmithKline) is one such TLR4 agonist that has been approved for use in human vaccines, such as Cervarix and Shingrix. Due to the heterogeneous nature of biologically derived MPL and the need for safer and more potent adjuvants, our groups have developed the novel TLR4 agonist candidates, BECC438 and BECC470 using the Bacterial Enzymatic Combinatorial Chemistry (BECC) platform. BECC438 and BECC470 have been included in studies to test their adjuvant potential and found to be effective in vaccines against both viral and bacterial disease agents. Here, we report detailed biophysical characterization of BECC438 and BECC470 purified from a biological source (BECC438b and BECC470b, respectively) and synthesized chemically (BECC438s and BECC470s, respectively). Both BECC438s and BECC470s have identical acyl chain configurations, BECC438s is bis-phosphorylated and BECC470s is mono-phosphorylated with the removal of the 4' phosphate moiety. We determined the phase transition temperatures for the acyl chains of BECC438b and BECC470b and found them to be different from those exhibited by their synthetic counterparts. Furthermore, the phosphate groups of BECC438b and BECC470b are more highly hydrated than are those of BECC438s and BECC470s. In addition to exploring the BECC molecules' biophysical features in aqueous solution, we explored potential formulation of BECC438 and BECC470 with the aluminum-based adjuvant Alhydrogel and as part of an oil-in-water emulsion (Medimmune Emulsion or ME). All of the lipid A analogues could be fully absorbed to Alhydrogel or incorporated onto ME. Surprisingly, the BECC470s molecule, unlike the others, displayed a nearly baseline signal when monitored using a Limulus amebocyte lysate (LAL) endotoxin detection system. Despite this, it was shown to behave as an agonist for human and mouse TLR4 when tested using multiple cell-based systems. This work paves the way for further formulation optimization of two chemically defined TLR4 agonists that are showing great promise as vaccine adjuvants.

Immunogenicity and protective efficacy of nanoparticle formulations of L-SseB against Salmonella infection.

Salmonella enterica, a Gram-negative pathogen, has over 2500 serovars that infect a wide range of hosts. In humans, S. enterica causes typhoid or gastroenteritis and is a major public health concern. In this study, SseB (the tip protein of the Salmonella pathogenicity island 2 type III secretion system) was fused with the LTA1 subunit of labile-toxin from enterotoxigenic E. coli to make the self-adjuvanting antigen L-SseB. Two unique nanoparticle formulations were developed to allow multimeric presentation of L-SseB. Mice were vaccinated with these formulations and protective efficacy determined via challenging the mice with S. enterica serovars. The polysaccharide (chitosan) formulation was found to elicit better protection when compared to the squalene nanoemulsion. When the polysaccharide formulation was used to vaccinate rabbits, protection from S. enterica challenge was elicited. In summary, L-SseB in a particulate polysaccharide formulation appears to be an attractive candidate vaccine capable of broad protection against S. enterica.

Self-assembled renewable nano-sized pentacyclic triterpenoid maslinic acids in aqueous medium for anti-leukemic, antibacterial and biocompatibility studies: An insight into targeted proteins-compound interactions based mechanistic pathway prediction through molecular docking.

Maslinic acid is a naturally occurring dihydroxy, mono-carboxy bioactive triterpenoid. Its bulky structure was the main hindrance in the path of biological activity. Sodium and potassium salts of nano-sized triterpenoid maslinic acid were prepared from maslinic acid and its self-assembly property was studied in aqueous and aqueous-organic binary liquid mixtures. Morphology of the compounds studied by Field Emission Scanning Electron Microscopy (FESEM), Atomic Force Microscopy (AFM), High Resolution Transmission Electron Microscopy (HRTEM), Optical Microscopy, Fourier Transform Infrared Spectroscopy (FTIR) and X-ray diffraction (XRD) revealed vesicular morphology of the self-assemblies. Selective cytotoxicity was performed in leukemic (K-562 and KG-1a) and PBMC cells. Among the three self-assemblies (maslinic acid 1, sodium maslinate 2 and potassium maslinate 3), sodium maslinate 2 showed better antileukemic efficacy. Sodium maslinate 2 induced apoptosis in leukemic cells by elevating ROS levels and disrupting the cellular antioxidant system. From the in-silico studies, it was confirmed that 2 interacted with extrinsic and intrinsic apoptotic proteins of leukemic cells and killed those cells by inducing apoptotic pathways. The compounds 1, 2 and 3 showed significant antibacterial efficacy against E.coli strain through binding with several periplasmic membrane fusion protein (MFP) and limiting the efflux system leading to arrestation of antimicrobial resistance.