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Background: Morbidity and mortality from dengue virus (DENV) is rapidly growing in the large populations of south Asia. Few formal evaluations of candidate dengue vaccine candidates have been undertaken in India, Pakistan, or Bangladesh. Tetravalent vaccines must be tested for safety and immunogenicity in all age groups and in those previously exposed and naive to DENV infections. TV005 is a live, attenuated tetravalent dengue vaccine. We evaluated the safety and immunogenicity of a single dose of TV005 across age groups in dengue-endemic Bangladesh., Methods: We performed a randomised, placebo-controlled age de-escalating clinical trial of TV005 at a single clinical site in dengue-endemic Dhaka, Bangladesh, following a technology transfer from the USA. Healthy (as determined by history, clinical examination, and safety laboratory test results) volunteers aged 1-50 years were randomly assigned 3:1 (stratified by four age groups) to receive a single dose of TV005 vaccine or placebo. Participants were followed up for 3 years. The study was double blind and was unmasked at day 180; outcome assessors, clinic staff, and volunteers remained blind throughout. Primary outcomes were safety, evaluated per-protocol as proportion of volunteers with solicited related adverse events of any severity through 28 days post dosing, and post-vaccination seropositivity by day 180 using serotype-specific neutralising antibodies (PRNT 50 ≥10). Secondary outcomes included viremia, impact of past dengue exposure, and durability of antibody responses. This study is registered with Clinicaltrials.gov, NCT02678455, and is complete., Findings: Between March 13, 2016, and Feb 14, 2017, 192 volunteers were enrolled into four age groups (adults [18-50 years; 20 male and 28 female], adolescents [11-17 years; 27 male and 21 female], children [5-10 years; 15 male and 33 female], and young children [1-4 years; 29 male and 19 female]) with 48 participant per group. All participants were Bangladeshi. Vaccination was well tolerated and most adverse events were mild. Rash was the most common vaccine-associated solicited adverse event, in 37 (26%) of 144 vaccine recipients versus six (12%) of 48 placebo recipients; followed by fever in seven (5% of 144) and arthralgias in seven (6% of 108), which were only observed in vaccine recipients. Post-vaccine, volunteers of all ages (n=142) were seropositive to most serotypes with 118 (83%) seropositive to DENV 1, 141 (99%) to DENV 2, 137 (96%) to DENV 3, and 124 (87%) to DENV 4, overall by day 180. Post-vaccination, viraemia was not consistently found and antibody titres were higher (10-15-fold for DENV 1-3 and 1·6-fold for DENV 4) in individuals with past dengue exposure compared with the dengue-naive participants (DENV 1 mean 480 [SD 4·0] vs 32 [2·4], DENV 2 1042 [3·2] vs 105 [3·1], DENV 3 1406 [2·8] vs 129 [4·7], and DENV 4 105 [3·3] vs 65 [3·1], respectively). Antibody titres to all serotypes remained stable in most adults (63-86%) after 3 years of follow-up. However, as expected for individuals without past exposure to dengue, titres for DENV 1, 3, and 4 waned by 3 years in the youngest (1-4 year old) cohort (69% seropositive for DENV 2 and 22-28% seropositive for DENV 1, 3, and 4)., Interpretation: With 3 years of follow-up, the single-dose tetravalent dengue vaccine, TV005, was well tolerated and immunogenic for all four serotypes in young children to adults, including individuals with no previous dengue exposure., Funding: National Institutes of Health-National Institute of Allergy and Infectious Diseases Intramural Research Program and Johns Hopkins University., Translation: For the Bangla translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests M-CRW, KKP, MC, DMD, DMB, SAD, FN, and BDK are employed by the University of Vermont Larner College of Medicine (UVM), Burlington, VT, USA, which was the recipient of research funding from the National Institutes of Health (NIH) and Johns Hopkins University for this work. SSW is employed by the NIH, which partially funded this work. APD is employed by Johns Hopkins University, which receives funding from the NIH for dengue research. MSA, MA, SA, KG, FQ, and RH are employed by the icddr, b which received funding from UVM for the conduct of this research., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In this study, we proposed 'switching ultrasonic amplitude' as a new strategy of applying ultrasonic energy to prepare a hybrid of buckminsterfullerene (C 60 ) and gallium oxide (Ga 2 O 3 ), C 60 /Ga 2 O 3 . In the proposed method, we switched the ultrasonic amplitude from 25% to 50% (by 5% amplitude per 10 min, within 1 h of ultrasonic irradiation) for the sonochemical treatment of a heterogeneous aqueous mixture of C 60 and Ga 2 O 3 by a probe-type ultrasonic horn operating at 20 kHz. We found that compared to the conventional techniques associated with high amplitude oriented ultrasonic preparation of functional materials, switching ultrasonic amplitude can better perform in preparing C 60 /Ga 2 O 3 with respect to avoiding titanium (Ti) as an impurity generating from the tip erosion of a probe-type ultrasonic horn during high amplitude ultrasonic irradiation in an aqueous medium. Based on SEM/EDX analysis, the quantity of Ti (wt.%) in C 60 /Ga 2 O 3 prepared by the proposed technique of switching ultrasonic amplitude was found to be 1.7% less than that prepared at 50% amplitude of ultrasonic irradiation. The particles of C 60 /Ga 2 O 3 prepared by different modes of amplitude formed large (2-12 μm) aggregates in their solid phase.Whereas, in the aqueous medium, they were found to disperse in their nano sizes. The minimum particle size of the as-synthesized C 60 /Ga 2 O 3 in an aqueous medium prepared by the proposed method of switching ultrasonic amplitude reached to approximately 467 nm. Comparatively, the minimum particle sizes were approximately 658 nm and 144 nm, using 25% and 50% amplitude, respectively. Additionally, Ga 2 O 3 went under hydration during ultrasonic irradiation. Moreover, due to the electron cloud interference from C 60 in the hybrid structure of C 60 /Ga 2 O 3 , the vibrational modes of Ga 2 O 3 were Raman inactive in C 60 /Ga 2 O 3 ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Oral, live-attenuated rotavirus vaccines suffer from impaired immunogenicity and efficacy in low-income countries. Increasing the inoculum of vaccine might improve vaccine response, but this approach has been inadequately explored in low-income countries., Methods: We performed a double-blind, parallel group, randomized controlled trial from June 2017 through June 2018 in the urban Mirpur slum of Dhaka, Bangladesh to compare vaccine take (primary outcome) among healthy infants randomized to receive either the standard dose or double the standard dose of oral Rotarix (GlaxoSmithKline) vaccine at 6 and 10 weeks of life. Infants with congenital malformations, birth or enrollment weight <2000 gm, known immunocompromising condition, enrollment in another vaccine trial, or other household member enrolled in the study were excluded. Infants were randomized using random permuted blocks. Vaccine take was defined as detection of post-vaccination fecal vaccine shedding by real-time reverse transcription polymerase chain reaction with sequence confirmation or plasma rotavirus-specific immunoglobulin A (RV-IgA) seroconversion 4 weeks following the second dose., Results: 220 infants were enrolled and randomized (110 per group). 97 standard-dose and 92 high-dose infants completed the study per-protocol. For the primary outcome, no significant difference was observed between groups: vaccine take occurred in 62 (67%) high-dose infants versus 69 (71%) standard-dose infants (RR 0.92, 95% CI 0.67-1.24). However, in post-hoc analysis, children with confirmed vaccine replication had significantly increased RV-IgA responses, independent of the intervention. No significant adverse events related to study participation were detected., Conclusions: Administration of double the standard dose of an oral, live-attenuated rotavirus vaccine (Rotarix) did not improve vaccine take among infants in urban Dhaka, Bangladesh. However, improved immunogenicity in children with vaccine replication irrespective of initial inoculum provides further evidence for the need to promote in-host replication and improved gut health to improve oral vaccine response in low-income settings. ClinicalTrials.gov: NCT02992197., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Calpain-mediated tau cleavage into the neurotoxic tau 45-230 fragment plays an important role in Alzheimer's disease (AD). This tau fragment accumulates mainly in the cytoplasm of degenerating neurons. However, subcellular localization studies indicated that a pool of tau 45-230 associates with the cytoskeleton in hippocampal neurons. In the present study, we assessed whether such localization could underlie tau 45-230 neurotoxic effects. Quantitative Western blot analysis showed decreased levels of full-length tau bound to microtubules in tau 45-230 -expressing hippocampal neurons when compared to controls. In addition, the presence of this tau fragment induced a transient increase in tyrosinated tubulin, a marker of unstable microtubules, followed by a significant decrease in the levels of this tubulin isoform. The data obtained also showed a significant reduction in actin filaments in tau 45-230 -expressing neurons. These changes in microtubules and actin filaments correlated with delayed neurite elongation and axonal differentiation in the presence of this tau fragment. Together, these results suggest that tau 45-230 could exert its toxic effects, at least in part, by modifying the composition of the neuronal cytoskeleton and impairing neurite elongation in neurons undergoing degeneration., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

The main objective of this review is to derive the salient features of previously developed ultrasound-assisted methods for hydroxylating graphene and Buckminsterfullerene (C 60 ). The pros and cons associated to ultrasound-assisted synthesis of hydroxy-carbon nanomaterials in designing the strategical methods for the industrial bulk production are also discussed. A guideline on the statistical methods has also been considered to further provide the scopes towards the application of the previously reported methods. Irrespective of many useful methods that have been developed in order to functionalize C 60 and graphene by diverse oxygenated functional groups e.g. epoxide, hydroxyl, carboxyl as well as metal/metal oxide via a combination of organic chemistry and sonochemistry, there is no report dealing exclusively on the application of ultrasonic cavitation particularly to synthesising polyhydroxylated carbon nanomaterials. On this context, this review emphasizes in investigating the critical aspects of sono-nanochemistry and the statistical approaches to optimize the variables in the sonochemical process towards a large-scale synthesis of polyhydroxylated graphene and C 60 ., (Copyright © 2018. Published by Elsevier B.V.)

The dysregulation of posttranslational modifications of the microtubule-associated protein (MAP) tau plays a key role in Alzheimer's disease (AD) and related disorders. Thus, we have previously shown that beta amyloid (Aβ)-induced neurotoxicity was mediated, at least in part, by tau cleavage into the tau 45-230 fragment. However, the mechanisms underlying the toxicity of tau 45-230 remain unknown. To get insights into such mechanisms, we first determined the subcellular localization of this tau fragment in hippocampal neurons. Tau 45-230 was easily detectable in cell bodies and processes extended by these neurons. In addition, cell extraction experiments performed using Triton X-100 and saponin showed that a pool of tau 45-230 was associated with the cytoskeleton and the cytoskeleton plus membrane-bound organelles, respectively, in cultured hippocampal neurons. Furthermore, they suggested that these associations were independent of the presence of full-length tau. We also assessed whether this tau fragment could alter axonal transport. Our results indicated that tau 45-230 significantly reduced the number of organelles transported along hippocampal axons. This altered axonal transport did not correlate with changes in the total number of organelles present in these cells or in motor protein levels. Together these results suggested that tau 45-230 could exert its toxic effects by partially blocking axonal transport along microtubules thus contributing to the early pathology of AD., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

Glassy carbon particles (millimetric or micrometric sizes) dispersions in water were treated by ultrasound at 20kHz, either in a cylindrical reactor, or in a "Rosette" type reactor, for various time lengths ranging from 3h to 10h. Further separations sedimentation allowed obtaining few nanoparticles of glassy carbon in the supernatant (diameter <200nm). Thought the yield of nanoparticle increased together with the sonication time at high power, it tended to be nil after sonication in the cylindrical reactor. The sonication of glassy carbon micrometric particles in water using "Rosette" instead of cylindrical reactor, allowed preparing at highest yield (1-2wt%), stable suspensions of carbon nanoparticles, easily separated from the sedimented particles. Both sediment and supernatant separated by decantation of the sonicated dispersions were characterized by laser granulometry, scanning electron microscopy, X-ray microanalysis, and Raman and infrared spectroscopies. Their multiscale organization was investigated by transmission electron microscopy as a function of the sonication time. For sonication longer than 10h, these nanoparticles from supernatant (diameter <50nm) are aggregated. Their structures are more disordered than the sediment particles showing typical nanometer-sized aromatic layer arrangement of glassy carbon, with closed mesopores (diameter ∼3nm). Sonication time longer than 5h has induced not only a strong amorphization (subnanometric and disoriented aromatic layer) but also a loss of the mesoporous network nanostructure. These multi-scale organizational changes took place because of both cavitation and shocks between particles, mainly at the particle surface. The sonication in water has induced also chemical effects, leading to an increase in the oxygen content of the irradiated material together with the sonication time., (Copyright © 2016 Elsevier B.V. All rights reserved.)