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BackgroundPrevention of relapse for adults with Acute Myeloid Leukemia (AML) in first remission (CR1) is the most common indication for allogeneic hematopoietic cell transplantation (alloHCT). Measurable residual disease (MRD) detection has been associated with higher relapse rates, but testing is not standardized. Establishment of validated AML MRD criteria would allow harmonization across centers facilitating clinical trials and generalizable practice guidelines.MethodsPatients aged 18 or older who underwent first alloHCT forFLT3, NPM1, IDH1, IDH2and/orKITmutated AML in CR1 were eligible for this multicenter study. Residual mutations detected in remission using ultra-deep error-corrected next-generation DNA-sequencing (NGS-MRD) associated with increased relapse risk were validated in a second independent cohort. The impact of baseline characteristics on NGS-MRD results was evaluated.ResultsPre-conditioning CR1 blood samples from 1075 patients were tested. Detection of residualNPM1and/orFLT3-ITD mutations before alloHCT was associated with worse outcomes after transplantation in both discovery (patients transplanted 2013-2017) and validation (patients transplanted 2018-2019) cohorts. In multivariate Cox regression analysis detection of residualNPM1m (relapse; HR: 4.9, 3.5-7.0, PFLT3-ITD (relapse: HR: 4.2, 3.1-5.7, PConclusionsDetection of residualNPM1and/orFLT3-ITD mutations in the blood of patients undergoing alloHCT for AML in CR1 is associated with increased relapse and worse survival. In those undergoing reduced intensity conditioning, melphalan may reduce the risk associated with testing NGS-MRD positive prior to transplantation. more...

Lawal et al report on a 45-fold increase in secondary hematologic malignancy in 120 patients following hematopoietic stem cell transplantation (HSCT) for sickle cell disease (SCD), comparable to what has been reported following gene therapy. Notably, the cohort is enriched for older patients and for haploidentical transplant recipients with mixed chimerism following HSCT. These data further support the idea that pre-existing premalignant myeloid clones undergo clonal selection in the setting of nonmyeloablative HSCT and contribute to secondary malignancy. more...

Invasive fungal infections (IFIs) are an important cause of neonatal mortality and morbidity. A total of 5% of IFIs are complicated by fungal endocarditis. Mortality can be as high as 50%. We present a preterm, very low birth weight infant with infective endocarditis. Echocardiography showed a large pedunculated vegetation attached to the inferior vena cava and right atrium junction. Baby had Candida tropicalis in his blood cultures and was managed conservatively with antifungals. Surgery although planned was not possible considering baby being preterm with very low birth weight. more...

ImportancePreventing relapse for adults with acute myeloid leukemia (AML) in first remission is the most common indication for allogeneic hematopoietic cell transplant. The presence of AML measurable residual disease (MRD) has been associated with higher relapse rates, but testing is not standardized.ObjectiveTo determine whether DNA sequencing to identify residual variants in the blood of adults with AML in first remission before allogeneic hematopoietic cell transplant identifies patients at increased risk of relapse and poorer overall survival compared with those without these DNA variants.Design, Setting, and ParticipantsIn this retrospective observational study, DNA sequencing was performed on pretransplant blood from patients aged 18 years or older who had undergone their first allogeneic hematopoietic cell transplant during first remission for AML associated with variants in FLT3, NPM1, IDH1, IDH2, or KIT at 1 of 111 treatment sites from 2013 through 2019. Clinical data were collected, through May 2022, by the Center for International Blood and Marrow Transplant Research.ExposureCentralized DNA sequencing of banked pretransplant remission blood samples.Main Outcomes and MeasuresThe primary outcomes were overall survival and relapse. Day of transplant was considered day 0. Hazard ratios were reported using Cox proportional hazards regression models.ResultsOf 1075 patients tested, 822 had FLT3 internal tandem duplication (FLT3-ITD) and/or NPM1 mutated AML (median age, 57.1 years, 54% female). Among 371 patients in the discovery cohort, the persistence of NPM1 and/or FLT3-ITD variants in the blood of 64 patients (17.3%) in remission before undergoing transplant was associated with worse outcomes after transplant (2013-2017). Similarly, of the 451 patients in the validation cohort who had undergone transplant in 2018-2019, 78 patients (17.3%) with residual NPM1 and/or FLT3-ITD variants had higher rates of relapse at 3 years (68% vs 21%; difference, 47% [95% CI, 26% to 69%]; HR, 4.32 [95% CI, 2.98 to 6.26]; P P Conclusions and RelevanceAmong patients with acute myeloid leukemia in first remission prior to allogeneic hematopoietic cell transplant, the persistence of FLT3 internal tandem duplication or NPM1 variants in the blood at an allele fraction of 0.01% or higher was associated with increased relapse and worse survival compared with those without these variants. Further study is needed to determine whether routine DNA-sequencing testing for residual variants can improve outcomes for patients with acute myeloid leukemia. more...

This study aimed to identify the intracellular binding partner of a unique class of staphylococcal secreted exotoxins called superantigen-like proteins (SSL) from human macrophage and keratinocyte cell lysates. Here, we report that SSL1 specifically binds to human extracellular signal-regulated kinase 2 (hERK2), an important stress-activated kinase in mitogen-activated protein kinase signaling pathways. Western blot and in vitro binding studies with recombinant hERK2 confirmed the binding interaction of SSL1, SSL7, and SSL10 with hERK2. Moreover, the SSLs-hERK2 interaction was validated biochemically by ELISA. Our finding shows that SSLs play a novel role by binding with host cell MAP kinase signaling pathway protein. Understanding the SSL-hERK2 interaction will also provide a basis for designing SSL-based peptide inhibitors of hERK2 in cancer therapy. more...

In view of many promising applications of gold nanoclusters (AuNCs), nanothermometry is an important field of research in biology and medicine. Here, we demonstrate the temperature dependent photophysical properties of highly luminescent green emitting 6-aza-2-thiothymine/l-arginine-stabilized Au nanosclusters (ATT/Arg Au NCs) by using steady state and time-resolved photoluminescence spectroscopy. Significantly, thermoresponsive properties of these highly photostable and biocompatible Au NCs are reversible, which endow the probe for further bioanalytical applications with great prospects. Additionally, protein-NC interaction mechanism has been elucidated in vitro and in vivo that dictates the complex behavior of the NCs with living organisms. These ultrasmall Au NCs are observed to accumulate in the cellular cytoplasm by translocating through the membrane as evidenced from the confocal laser scanning microscopy (CLSM). In vivo temperature sensing examined with human osteosarcoma cell line (MG-63 cell) by employing fluorescence lifetime imaging microscopy (FLIM) technique reveals the optimistic application of these lifetime-based nanosensors in biomedicine and biotechnology. more...

Peripherally inserted central catheters (PICC) are commonly used in the neonatal intensive care unit. They help in administering fluids, nutrition, and antibiotics. They have a lower risk for injury, infection, and thrombosis compared to central venous catheters. PICC fracture in a neonate has been rarely documented. We present a pre term neonate who had a PICC fracture remnant in the right atrium which was diagnosed following a contrast x ray and echocardiography. The PICC was removed percutaneously by our intervention pediatric cardiologist. All central venous access lines should be carefully monitored in the neonatal intensive care unit for risk of complications. more...

A term infant girl with uneventful antenatal history had an erythematous rash followed by fever from day 8. She was diagnosed with late-onset sepsis and was treated accordingly. She received immunoglobulin for persistent thrombocytopenia, after which there was transient improvement. The patient was transferred to our hospital on day 25 after recurrence of fever, watery diarrhea, and a generalized maculopapular rash. On admission, she had tachycardia, tachypnoea, anemia, thrombocytopenia, hypoalbuminemia, and generalized edema. Reverse transcriptase–polymerase chain reaction results for coronavirus disease 2019 (COVID-19) was positive. Within 12 hours of admission, she developed cardiogenic shock with pulmonary edema and needed invasive ventilation. Echocardiography revealed ejection fraction of 40% with mild pericardial effusion. N-terminal pro–brain natriuretic peptide was 33000 g/L, D-dimer 16500 µg/L, and ferritin 16000 ng/mL. Methylprednisolone, immunoglobulin, and enoxaparin was started, with a diagnosis of multisystem inflammatory syndrome in children, associated with COVID-19. She developed seizures, pulmonary hemorrhage, and cardiac arrest the following day, along with acute kidney injury. She was extubated after 5 days. Steroid was stopped after 5 days because she developed hypertension and echocardiography had normalized. Five days after extubation, she again developed respiratory distress and was ventilated again for 2 days. Echocardiography revealed moderate left ventricular dysfunction, along with secondary elevation of ferritin. Methylprednisolone was restarted and continued for 5 days followed by tapering dose of oral prednisolone, on which she was finally discharged. Although mild myocarditis with COVID-19 has been reported, multisystem inflammatory syndrome in children in a newborn with refractory myocarditis, along with gastrointestinal and renal manifestations, is a rare entity. Dermatologic manifestation of neonatal COVID-19 is also unique. more...

Aim: The aim of this study was to assess the clinico-epidemiological profile, etiology, and imaging findings in neonatal stroke (NS). Materials and Methods: This was a retrospective, observational study on neonates presenting with stroke between August 2014 and July 2016 to a tertiary care hospital in eastern India. Results: In all, 43 neonates were analyzed, with a male-to-female ratio of 2.3:1. About 88% babies were born at term and the rest were preterm. In 37%, the etiology of stroke was related to hypoxic injury, 21% had sepsis, and 35% had idiopathic causes. Seizures were the most common mode of presentation (62%) followed by poor feeding, abnormal tone, recurrent apnea, encephalopathy, and hemiparesis. There was an almost equal prevalence of ischemic stroke (53%) and hemorrhagic stroke (HS). Middle cerebral artery territory was the primary site of involvement in arterial ischemic stroke, and intra ventricular hemorrhage was the most common presentation of HS. Conclusion: NS is an acute emergency with high morbidity and mortality. Magnetic resonance imaging helps in diagnosis and prognostication in the absence or paucity of focal neurological signs in neonates. more...

To compare the characteristics and short-term outcomes in extremely preterm infants, who developed necrotizing enterocolitis (NEC) following a packed red blood cell transfusion (pRBC) within 48 h (TANEC), with those who developed NEC beyond 48 h (non-TANEC).A single-center retrospective cohort study in a Tertiary neonatal intensive care unit in the UK over a 5-year period.Extremely premature infants (23-27 weeks gestation) were selected. TANEC and non-TANEC incidence were calculated from the confirmed NEC group (defined as modified Bell's stage II and beyond). The characteristics and short-term outcomes of infants with TANEC in the first 8 weeks of life were compared to infants with non-TANEC.Incidence of confirmed NEC was 14% (28/207). On further subgroup analysis of the confirmed NEC cases, 46% (13/28) of infants were identified with TANEC and 54% (15/28) with non-TANEC. The incidence of TANEC did not correlate with the number of antecedent pRBC transfusions or the pre-transfusion median hemoglobin (Hb) levels. There were no significant differences in characteristics between the TANEC and non-TANEC groups. Infants within the TANEC group required more intensive neonatal care support, greater surgical intervention (A significantly worse clinical course and short-term outcome was observed in the TANEC group when compared with the non-TANEC group. more...

The dye encapsulated metal–organic frameworks (MOFs) are of interest for their practical applications such as light-emitting diodes, temperature sensing, and microlasers. However, very few MOFs have been reported to date where the dye moiety is utilized as one of the components of the framework. Fluorescein dye (FSD) doped materials have an ability to emit various colors such as red, green, and yellow depending upon their tautomeric form and external stimuli. In anticipation of light-emitting devices, three FSD-based novel MOFs, namely, {[Co2(FSD)2(H2O)4]·H2O·MeOH}n, FSDCo; {[Mn2(FSD)2(H2O)4]·H2O·MeOH}n, FSDMn; and {[Cd2(FSD)2(H2O)3(MeOH)]·2(H2O)}n, FSDCd, have been designed and synthesized. These crystalline materials were shown to exhibit multicolor light-emitting behavior and reversible green to brown piezochromism, implying their potential to act as fluorescent switches, mechanosensors, and security papers. Further, these crystalline MOFs were also shown to exhibit a rare optical phenomenon called ple... more...

We have elucidated the role of unsaturated fatty acid in the in vitro model phospholipid membrane and in vivo live cell membrane. Fluorescence microscopy and time-resolved fluorescence spectroscopy have been employed to uncover how modulation of vesicle bilayer fluidity persuades structural transformation. This unsaturation induced structural transformation due to packing disorder in bilayer has been delineated through spatially resolved fluorescence lifetime imaging microscopy (FLIM) and fluorescence polarization or anisotropy imaging microscopy (FPIM/FAIM). Structure-function relationship of phospholipid vesicle is also investigated by monitoring intervesicular water dynamics behavior, which has been demonstrated by temporally resolved fluorescence spectroscopy (TRFS) techniques. Nevertheless, it has also been manifested from this study that loss of rigidity in bilayer breaks down the strong hydrogen bond (H-bond) network around the charged lipid head groups. The disruption of this H-bond network increases the bilayer elasticity, which helps to evolve various kinds of vesicular structure. Furthermore, the significant influence of unsaturated fatty acid on membrane bilayer has been ratified through in vivo live cell imaging. more...

A water-soluble dilithium salt BODIPY derivative (LiBDP) with appended dicarboxylate pseudo-crown ether [NO4] coordinating sites has been designed, synthesized and characterized successfully for the selective and sensitive recognition of Cd2+ in aqueous media. The chemosensor exhibits a remarkable increase in fluorescence intensity as well as a distinct color change upon the addition of Cd2+ over other environmentally and biologically relevant metal ions in H2O. The fluorometric response of LiBDP is attributed to the metal chelation-enhanced fluorescence (MCHEF) effect which has been confirmed by a strong association constant of 2.57 ± 1.06 × 105 M−1 and Job's plot, indicating 1 : 1 binding stoichiometry between LiBDP and Cd2+. Frontier molecular orbital analysis (obtained from DFT studies) also illustrates the turn-on fluorescence of the probe by blocking photoinduced electron transfer (PET) after coordination to Cd2+. The probe can detect Cd2+ in a competitive environment up to a submicromolar level in a biologically significant pH range. The sensor is proved to be reversible and reusable by the alternative addition of Cd2+ followed by S2−. The OFF/ON/OFF sensing behavior is utilized to construct an INHIBIT molecular logic gate based on the two inputs of Cd2+ and S2− and a fluorescence intensity at 512 nm as an output. The test paper experiment demonstrates the practical utility of LiBDP to monitor Cd2+ in an aqueous sample. Finally, the sensing probe was utilized to monitor Cd2+ in living cells. more...

BACKGROUND: The pathogenesis of acute myeloid leukemia (AML) is often attributed to the presence of somatic allelic variant(s) in hematopoietic stem/progenitor cells. However, malignant clones may have heterogenous cell-surface immunophenotypes including overlap with non-malignant cells. While leukemia-associated immunophenotypes and difference from normal approaches are used for flow cytometric assessment during and after treatment, such analysis may underrepresent true leukemia disease burden. Assessments of AML measurable residual disease (MRD) using flow cytometry and molecular methods have been reported as discrepant. Single-cell RNA sequencing experiments have recently attempted to distinguish malignant cells based on gene expression and/or immunophenotypic profiles alone. We hypothesized that single-cell genotyping of mutated transcript(s) coupled with broad surface proteome and transcriptome profiling could provide an integrated multimodal method for AML characterization. METHODS: We adapted the previously reported "genotyping of transcriptomes" (PMID: 31270458) to identify cells carrying the NPM1 type A mutation commonly seen, and typically stable throughout the disease course, in AML. Healthy human peripheral blood mononuclear cells (PBMC) were mixed with an AML cell line carrying NPM1 type A mutation (OCI-AML3) at 7:3 ratio and labelled with 163 oligo-tagged antibodies. Single cell 3'v3 gene expression- (GEX), antibody derived tag- (ADT) and genotyping of NPM1 (GNPM) -libraries (10X Genomics) were sequenced on the NovaSeq 6000 (Illumina). Results were processed using Seurat 4.0 toolkit. RESULTS: In total, 72% (n=1680) of barcoded cells could be genotyped for NPM1. Of the genotyped cells, 59% (n = 986) were not NPM1 mutated. Visualization using Uniform Manifold Approximation and Projection (UMAP) showed separation of healthy PBMCs and OCI-AML3 cells using protein data, confirmed by annotation using NPM1 genotyping (Figure 1). We found a significant positive correlation between mRNA and corresponding cell surface protein expressions in non-mutated (Pearson's coefficient, r = 0.502, p = 6.87e-11) and NPM1 mutated (r= 0.392, p= 7.5e-7) cells. Compared to non-mutated, NPM1 mutated cells showed nearly 14-fold higher NPM1 transcript levels. In addition, a total 63 proteins were highly expressed on the surface of NPM1 mutated cells (Figure 2). Among these, CD33 and CD36 showed maximum 8-fold increase in expression. Other highly expressed proteins with at least >2.5-fold change were cell adhesion molecules (including CD328, CD155, and CD56), extracellular matrix binding proteins (CD49a/b) and interleukin receptor (CD123). CONCLUSION: Overall, our results demonstrate proof of principle that high-throughput cell surface proteome, transcriptome and genotyping analysis can be simultaneously performed to comprehensively and confidently characterize individual AML cells. Patient-specific multiomics data with broad cell-surface proteomic screening may allow novel target identification for monitoring and/or therapeutic intervention. Ongoing work will now use this methodology to characterize a cohort of NPM1 mutated AML patient samples. Figure 1 Figure 1. Disclosures Hourigan: Sellas: Research Funding. more...

Chronic myeloid leukemia is a stem cell disease with the presence of Philadelphia chromosome generated through reciprocal translocation of chromosome 9 and 22. The use of first- and second-generation tyrosine kinase inhibitors has been successful to an extent. However, resistance against such drugs is an emerging problem. Apart from several drug-resistant mechanisms, drug influx/efflux ratio appears to be one of the key determinants of therapeutic outcomes. In addition, intracellular accumulation of drug critically depends on cell membrane fluidity and lipid raft dynamics. Previously, we reported two novel cell-penetrating peptides (CPPs), namely, cationic IR15 and anionic SR11 present in tryptic digest of Abrus agglutinin. Here, the potential of IR15 and SR11 to influence intracellular concentration of imatinib has been evaluated. Fluorescent correlation spectroscopy and lifetime imaging were employed to map membrane fluidity and lipid raft distribution following peptide-drug co-administration. Results show that IR15 and SR11 are the two CPPs which can modulate membrane fluidity and lipid raft distribution in K562 cells. Both IR15 and SR11 significantly reduce the viability of CML cells in the presence of imatinib by increasing the intracellular accumulation of the drug. more...

Ionic liquids (ILs) are considered as "green solvents" for more than 2 decades. However, recent studies suggest that some ILs exhibit greater toxicity compared to common solvents. As a proactive effort to better understand the molecular origin of the cytotoxicity, the work herein presents the systemic characterization of the interaction between model membrane composed of fatty acids and popular imidazolium-based hydrophilic IL. The fusion kinetics between the vesicles demonstrates the swelling of the vesicle. Further, membrane fluidity is determined using the isomerization kinetics of a lipophilic dye, merocyanine-540, and in the presence of IL, the fluidity of the inner water pool of the vesicle is increased. The results can be directly correlated to the cytotoxicity generated by IL in K562 cell, a human erythroleukemic cell line. High-concentration IL ruptures the cell membrane and causes membrane permeabilization. Thus, the results would help to facilitate the rational design of nontoxic ILs. more...

This was a prospective observational study to evaluate abnormalities in lipid profile in 50 children with transfusion dependent thalassemia. Dyslipidemia characterized by high triglycerides, low high density lipoprotein (HDL), and high total cholesterol: HDL ratio was noted. These pro atherogenic risk factors may be lead to significant cardiovascular morbidity in these patients. more...

This study aims to determine the incidence of sepsis in neonates operated for congenital diaphragmatic hernia and ascertain if the level or pattern of C-reactive protein (CRP) could be used to differentiate neonates with sepsis from noninfective inflammation. This study suggests that CRP patterns within the first 48-hours after surgical intervention for congenital diaphragmatic hernia could be used to differentiate neonates with noninfective inflammation from sepsis. A larger, multicentric study is needed to differentiate sepsis from inflammation on the basis of CRP rise and thereby help in avoiding unnecessary use of antibiotics. more...

Controllable self-assembly and understanding of the interaction between single metabolite fibrils and live-cell membranes have paramount importance in providing minimal treatment in several neurodegenerative disorders. Here, utilizing the nonlinear nature and peculiar hydrogen bonding behavior of the dimethyl sulfoxide (DMSO)-water mixture, the selective self-assembly of a single metabolite 5-fluorouracil (5-FU) is achieved. A direct correlation between water availability and selective self-assembly of 5-FU is ratified from the excited-state dynamics. The specific fibrillar structures of 5-FU exhibit a great potential to modulate live cell membrane fluidity and model membrane lipid distribution. After 5-FU fibril addition, a disorder of H-bonded water molecules arises several layers beyond the first hydration shell of the polar headgroups, which essentially modifies interfacial water structure and dynamics. Overall, our results shed light on the role of solvent to govern specific self-assembly and also lay the foundation accounting for the earlier stage of several diseases and multidrug resistance. more...

Disorders of central and peripheral nervous system should be considered in floppy infants with ventilator dependence. Workup for neuromuscular disorders should be undertaken in infants with hypotonia, weakness, contractures, feeding difficulties, or failed attempts at extubation. We present the case of a preterm infant with hypotonia and ventilator dependence where despite a positive result, further investigations were undertaken because of lack of clinical correlation. The infant had a rare combination of 2 neuromuscular conditions: X-linked myotubular myopathy and Duchenne muscular dystrophy. One was the reason for immediate clinical manifestation and the other influenced the prognosis and decision-making in determining reorientation of care. This case demonstrates the value of interpretation of a positive result that did not explain the clinical picture and warranted consideration of further diagnosis. This case also emphasizes the importance of discussions with family about the prognosis of 2 conditions that influenced decision making. more...

This hospital-based study describes the antibiotic sensitivity of 66 S. aureus isolates from the admitted children (age 0-18 y) in a tertiary hospital of Kolkata, India. Methicillin-resistant S. aureus constituted 16.7% (n=11) of the isolates. Clindamycin-resistance was observed in 60% and 82% of methicillin-sensitive and methicillin-resistant strains, respectively. more...

Targeted drug delivery is of paramount importance for cancer patients. Cell penetrating peptides (CPPs) have emerged as potent vehicles for this purpose. Herein, we demonstrate CPP- like properties of two peptides: NH2-SGASDDEEIAR-COOH (SR11) and NH2-ICSSHYEPTVRIGGR-COOH (IR15), derived from the tryptic digest of Abrus precatorius agglutinin. Both IR15 and SR11 were found to be non-toxic at lower doses (up to 50 μg/ml). These two peptides entered into HeLa cells through lipid raft-mediated endocytosis within 15 min and penetrated the nuclear membrane in 60 min of incubation. Co-treatment of peptides (20 μg/ml) and Imatinib (5 μM) in HeLa cells increased uptake of the drug by ∼ 55% and lowered the IC50 value to one-third in comparison to the drug added exclusively. However, co-treatment of TAT peptide (standard CPP) did not alter the Imatinib uptake significantly. In summary, we have identified two novel CPPs from tryptic digest of Abrus agglutinin which increased the cellular uptake of Imatinib upon co-administration. Further studies may result in deciphering a novel mode of drug delivery. more...

Ascaris infestation that too causing biliary obstruction is very rare in infancy even in endemic area. Adult Ascaris diameter (3-6 mm) is more than the average diameter of CBD in paediatric population, which is 1.27 +/- 0.67 mm. We are reporting a baby of seven months who presented with conjugated hypebilirubinemia and pancreatitis due to Round Worm in CBD. more...

An ex-30-week gestation, preterm male baby was admitted to a tertiary neonatal unit and noted to have increased ventilator requirements and diagnosed with sepsis. The baby also developed an abscess over the left elbow and over the xiphisternum along with a decrease in movement of the left hand and the right leg. Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus (SA) was isolated from the blood culture. A whole body MRI showed disseminated abscess with multiple foci in the lung, left elbow and over the xiphisternum. Disseminated sepsis with multiple septic foci has not been previously reported in neonates. We would like to highlight the fact that sepsis due to PVL toxin-producing SA can cause significant morbidity and mortality in neonates. Proper screening should be done to rule out septic foci in neonates. MRI is a good non-invasive investigation to document septic foci in a neonate and rule out multiorgan involvement. more...

A water-soluble dilithium salt BODIPY derivative (LiBDP) with appended dicarboxylate pseudo-crown ether [NO4] coordinating sites has been designed, synthesized and characterized successfully for the selective and sensitive recognition of Cd2+ in aqueous media. The chemosensor exhibits a remarkable increase in fluorescence intensity as well as a distinct color change upon the addition of Cd2+ over other environmentally and biologically relevant metal ions in H2O. The fluorometric response of LiBDP is attributed to the metal chelation-enhanced fluorescence (MCHEF) effect which has been confirmed by a strong association constant of 2.57 ± 1.06 × 105 M-1 and Job's plot, indicating 1 : 1 binding stoichiometry between LiBDP and Cd2+. Frontier molecular orbital analysis (obtained from DFT studies) also illustrates the turn-on fluorescence of the probe by blocking photoinduced electron transfer (PET) after coordination to Cd2+. The probe can detect Cd2+ in a competitive environment up to a submicromolar level in a biologically significant pH range. The sensor is proved to be reversible and reusable by the alternative addition of Cd2+ followed by S2-. The OFF/ON/OFF sensing behavior is utilized to construct an INHIBIT molecular logic gate based on the two inputs of Cd2+ and S2- and a fluorescence intensity at 512 nm as an output. The test paper experiment demonstrates the practical utility of LiBDP to monitor Cd2+ in an aqueous sample. Finally, the sensing probe was utilized to monitor Cd2+ in living cells. more...

Background The UK on 01 September 2015 became the first country to introduce Meningococcal B (Bexsero) vaccine into the national infant immunisation programme. Bexsero is recommended for all infants as part of their routine vaccinations at ages 2, 4 and 12 months alongside other regular vaccines. Bexsero is highly immunogenic and is estimated to protect against 73%–88% of MenB strains causing invasive meningeal disease (IMD) in England and Wales1. Objective We retrospectively evaluated tolerability of Bexsero vaccine on preterm babies in our neonatal intensive care unit. Methods Retrospective observational study comparing tolerability of the vaccines in the two time periods, before (Period 1, n=13) and following (Period 2, n=13) the introduction of the new vaccine (Bexsero) in September 2015. We inspected the clinical status 48 hours prior to and 48 hours post immunisation to evaluate vaccine tolerance during these two time periods. Results Before introduction of Men B vaccine, there was convincingly low levels of side effects in our babies following routine immunisation. After introduction of MenB vaccine, 46% (6/13) of babies became unwell within 24–48 hours of immunisation; 30% (4/13) needed escalation in respiratory support. 15% (2/13) needed rescue ventilation after Bexsero vaccination. Conclusions We hypothesised that all babies immunised with Bexsero alongside regular vaccines will remain clinically stable and will tolerate the vaccines without any appreciable side effects. 46% of our babies became unwell following the combined MenB programme, raising speculations about safety profile of the Bexsero in preterm infants. Precautionary monitoring following vaccination is recommended. Larger studies are needed to ensure safety of Bexsero vaccine in preterm babies. more...

To assess yield of imaging performed as per Indian Society of Pediatric Nephrology (ISPN) urinary tract infection (UTI) guideline. Ultrasonography (USG), voiding cystourethrography (VCUG) and dimercaptosuccinic-acid (DMSA) scintigraphy were performed in 183 children (age 0–5y) with first episode (age 0–1y) of UTI or recurrent (age more...

This observational, descriptive study was conducted on 260 dengue patients diagnosed as per the revised 2009 WHO guidelines in a tertiary-care hospital of eastern India between June and November 2015. Children were evaluated for clinical symptoms, signs, and laboratory parameters. Clinical variables viz., rash, nausea/vomiting, bleeding, oliguria, capillary leak and liver enlargement; and laboratory variables viz., rising haemoglobin, haematocrit, thrombocytopenia, blood urea, serum Creatinine, ALT, hypo albuminemia and cholesterol were found to be significantly associated with outcome. more...

Under physiological conditions, 5-fluorouracil (5-FU), an anticancer drug, self-assembles into fibrils by strong hydrogen-bonding network, whereas its N,N'-dimethyl derivative, 5-fluoro-1,3-dimethyluracil (5-FDMU), does not make fibrils due to lack of strong hydrogen-bonding motif. In vitro, 5-FU self-assembly is sensitive to physicochemical conditions like the pH and ionic strength of the solution, which tune the strength of the noncovalent driving forces. Here we report a surprising finding that the buffer, which is necessary to control the pH and is typically considered to be inert, also significantly influences 5-FU self-assembly, which indicates an important role of counterions in the fibril formation. We have also monitored concentration- and time-dependent fibrillar growth of 5-FU. Again, fibril growth process is probed under dynamic conditions using microfluidic platform. The self-assembly of 5-FU compared with its N,N'-dimethyl derivative shows lower cytotoxicity to the cultured human erythroleukemic cells (K562 cells), which plausibly states the reason behind the greater effectiveness of 5-FU derivative drugs than 5-FU itself. more...

Brucella has been known to cause pyrexia of unknown origin. 9-year-old boy with fever and abdominal pain; multiple abscesses within the liver on ultrasonography. IgM Antibodies against Brucella were raised in his serum sample, and Brucella serum agglutination test was positive. Immunological work-up suggested selective IgA deficiency. Reduction in size following treatment with trimethoprim-sulphamethoxazole, amikacin and doxycycline. Brucellosis should be considered as an etiology of liver abscess in patients not responding to conventional antibiotics. more...

As an emerging category of fluorescent metal nanoclusters (NCs), protein-based NCs are considered as one of the promising candidates for the biomedical applications because of their luminescent properties and inherent biocompatibilities. Protein-capped silver NCs impregnated onto graphene oxide (GO) sheets can be internalized into the K562 cell, a human erythroleukemic cell line, and the Ag NCs/GO assembly can act as a synergistic drug carrier for Imatinib, a first-generation tyrosine kinase inhibitor. Further, Ag NCs adsorbed on GO have a great potential to be used as X-ray computer tomography (CT) imaging contrasting agents, and CT images show significant contrast enhancement of bone tissues in mice models. Overall, this assembly can exhibit great potential in the field of biomedical application and therapeutic studies. more...

Complete Blood Count (CBC) is a collection of the most commonly required clinical tests to assess the manifestations of pathological conditions in blood. The existing clinical methods for this test are prohibitively expensive for the underprivileged global population due to the requirements of sophisticated instrumentation and trained personnel. To overcome these, we propose a unique low cost device as a blood cell counting platform. The method exploits the difference in densities of cells for separation in transparent microfluidic channels and implements label-free imaging method for counting the separated cells within the microfluidic disc. The device is a simple spinning disc to estimate the parameters such as hematocrit, hemoglobin, red blood cell (RBC), white blood cell (WBC), and platelet counts with an accuracy > 95% as compared to an automated hematology analyzer. The major advantages of this device over state of the art include multiple sample testing within a single biodegradable disc, simple design and fabrication techniques, potential automation thereby making it portable and eliminating the need of trained personnel, and most significantly, eliminating any need for downstream processing of the separated blood. These results may turn out to be of immense consequence towards developing novel point-of-care hematological analyzers for resource-constrained settings. more...

Dorsal dermal sinus (DDS) represents the spectrum of spinal dysraphism. Children may present with features of meningitis. A 13-month male child presented with features of meningitis and quadriparesis. Clinical examination revealed a small pit over the thoracic spine. MRI was suggestive of a DDS. Initially, the patient responded to antibiotics and methylprednisolone, which was given for resolving the mass effect. However, he had a recurrence of symptoms and underwent surgical exploration and resection of DSS with resolution of symptoms. Careful examination of the back is extremely essential in children with meningitis. Radiological investigation helps in visualisation of the DSS. Although rare in children, they may present with recurrent meningitis. more...

BACKGROUND Granulocytic sarcoma, an uncommon solid, extra-medullary tumor is a rare presentation of acute myeloid leukemia. CASE CHARACTERISTICS A seven-year old boy admitted to the hospital for treatment of leukemia having radiological findings of consolidation in one lung. OBSERVATION/INTERVENTION A bronchoalveolar lavage was done which was negative for tubercular, bacterial, and fungal infection but showed blast cells. OUTCOME On day seven of chemotherapy, a repeat chest x-ray showed resolution of the lesion. A high-resolution Computerized tomography of chest repeated after one month of induction showed resolution. MESSAGE A consolidation on chest radiograph in acute myeloid leukemia can be a granulocytic sarcoma of the lung; a bronchoalveolar lavage may be offered to confirm or refute this diagnosis. more...

This hospital-based study describes the antibiotic sensitivity of 66 S. aureus isolates from the admitted children (age 0-18 y) in a tertiary hospital of Kolkata, India. Methicillin-resistant S. aureus constituted 16.7% (n=11) of the isolates. Clindamycin-resistance was observed in 60% and 82% of methicillin-sensitive and methicillin-resistant strains, respectively. more...

Disseminated Tuberculosis (DTB) refers to tubercular involvement of two or more non-contiguous sites and is commonly associated with immunocompromised state. It is an unusual presentation of Tuberculosis (TB), especially in the absence of immunodeficiency. 1.4% of patients with Pulmonary Tuberculosis (PTB) develop ocular manifestations but many patients with ocular TB have no evidence of PTB. Tuberculosis can cause a wide variety of ophthalmic findings, ranging from the ocular surface through the optic nerve and to the central nervous system. In this article, we report a case of Disseminated Tuberculosis with ocular involvement in a 5years old female. Our case is unique for the presence of bilateral squint, unilateral nebular type of corneal opacity, bilateral iritis with posterior synechiae and cataract at the same time. It lays emphasis on the fact that a patient with tuberculosis should be screened for multiple foci. more...