Rotavirus trends and distribution of genotypes before and during COVID-19 pandemic era: Bangladesh, 2017-2021.

Rotavirus gastroenteritis is accountable for an estimated 128 500 deaths among children younger than 5 years worldwide, and the majority occur in low-income countries. Although the clinical trials of rotavirus vaccines in Bangladesh revealed a significant reduction of severe rotavirus disease by around 50%, the vaccines are not yet included in the routine immunization program. The present study was designed to provide data on rotavirus diarrhea with clinical profiles and genotypes before (2017-2019) and during the COVID-19 pandemic period (2020-2021). Fecal samples were collected from 2% of the diarrheal patients at icddr,b Dhaka hospital of all ages between January 2017 and December 2021 and were tested for VP6 rotavirus antigen using ELISA. The clinical manifestations such as fever, duration of diarrhea and hospitalization, number of stools, and dehydration and so on were collected from the surveillance database (n = 3127). Of the positive samples, 10% were randomly selected for genotyping using Sanger sequencing method. A total of 12 705 fecal samples were screened for rotavirus A antigen by enzyme immunoassay. Overall, 3369 (27%) were rotavirus antigen-positive, of whom children <2 years had the highest prevalence (88.6%). The risk of rotavirus A infection was 4.2 times higher in winter than in summer. Overall, G3P[8] was the most prominent genotype (45.3%), followed by G1P[8] (32.1%), G9P[8] (6.8%), and G2P[4] (6.1%). The other unusual combinations, such as G1P[4], G1P[6], G2P[6], G3P[4], G3P[6], and G9P[6], were also present. Genetic analysis on Bangladeshi strains revealed that the selection pressure (dN/dS) was estimated as <1. The number of hospital visits showed a 37% drop during the COVID-19 pandemic relative to the years before the pandemic. Conversely, there was a notable increase in the rate of rotavirus positivity during the pandemic (34%, p < 0.00) compared to the period before COVID-19 (23%). Among the various clinical symptoms, only the occurrence of watery stool significantly increased during the pandemic. The G2P[4] strain showed a sudden rise (19%) in 2020, which then declined in 2021. In the same year, G1P[8] was more prevalent than G3P[8] (40% vs. 38%, respectively). The remaining genotypes were negligible and did not exhibit much fluctuation. This study reveals that the rotavirus burden remained high during the COVID-19 prepandemic and pandemic in Bangladesh. Considering the lack of antigenic variations between the circulating and vaccine-targeted strains, integrating the vaccine into the national immunization program could reduce the prevalence of the disease, the number of hospitalizations, and the severity of cases.

Synthesis of Mono-, Di-, Tri-, and Tetra-cationic Pyridinium and Vinylpyridinium Modified [2.2]Paracyclophanes: Modular Receptors for Supramolecular Systems.

In this report, a new series of mono-, di-, tri-, and tetra-cationic pyridinium and vinyl pyridinium-modified [2.2]paracyclophanes as useful molecular tectons for supramolecular systems are described. Regioselective functionalization at specific positions, followed by resolution step and successive transformations through Pd-catalyzed Suzuki-Miyaura and Mizoroki-Heck cross-coupling chemistry furnish a series of modular PCP scaffolds. In our proof-of-concept study, on N-methylation, the PCPs bearing (cationic) pyridyl functionalities were demonstrated as useful molecular receptors in host-guest supramolecular assays. The PCPs on grafting with light-responsive azobenzene (-N=N-) functional core as side-groups impart photosensitivity that can be remotely transformed on irradiation, offering photo-controlled smart molecular functions. Furthermore, the symmetrical PCPs bearing bi-, and tetra-pyridyl functionalities at the peripheries have enormous potential to serve as ditopic and tetratopic 3D molecular tectons for engineering non-covalent supramolecular assemblies with new structural and functional attributes.

Arsenic Contamination of Groundwater Is Determined by Complex Interactions between Various Chemical and Biological Processes.

At a great many locations worldwide, the safety of drinking water is not assured due to pollution with arsenic. Arsenic toxicity is a matter of both systems chemistry and systems biology: it is determined by complex and intertwined networks of chemical reactions in the inanimate environment, in microbes in that environment, and in the human body. We here review what is known about these networks and their interconnections. We then discuss how consideration of the systems aspects of arsenic levels in groundwater may open up new avenues towards the realization of safer drinking water. Along such avenues, both geochemical and microbiological conditions can optimize groundwater microbial ecology vis-à-vis reduced arsenic toxicity.

Digitalized to reach and track: a retrospective comparison between traditional and conditional estimate of vaccination coverage and dropout rates using e-Tracker data below one-year children in Bangladesh during-COVID and pre-COVID period.

Background: With an impressive track record in expanding childhood immunization and an inclination to adopt digitalization in healthcare service delivery, Expanded Program on Immunization (EPI) Bangladesh piloted the e-Tracker intervention in Moulvibazar district and Dhaka South City Corporation (Zone-5) from 2019 till the end of 2021. Methods: We retrieved and analyzed the digitalized e-Tracker data of 114,194 infants born between January 1, 2019 and December 31, 2020, with help from Health Management Information System (HMIS) and UNICEF Bangladesh. Childhood vaccination coverage and dropout rates were determined using a 'Traditional approach' traditionally used by WHO and a 'Conditional technique' with a modified denominator. Using a multiple logistic regression model, we examined the effects of COVID-19, birth-cohorts, mother education, and location on vaccination rates (coverages & dropouts) to aid with informed decision-making by the policymakers. Findings: The conditional estimation method yielded a lower full vaccination coverage during pre-COVID period than the national and global reported coverage derived using the 'traditional method' (73.4% vs. 89.0% & 81.0%). As expected, while the coverage has decreased, the dropout rate increased "during-COVID" compared to the "pre-COVID" period. However, dropouts were estimated lower in the 'conditional method.' The average age (in months) for getting BCG was higher in Moulvibazar (∼2.5 months) than that in Dhaka (∼1.4 months). All birth-cohorts from 'the during-COVID period had about 30% lower odds of getting fully vaccinated than those from the 'pre-COVID' period. Interpretations: Age-cohort-specific analysis showed a decline in coverage rates before and during COVID, but e-Tracker didn't have enough data to draw additional conclusions. The server only stored the child's gender, the caregiver's monthly salary, and the mother's education. It didn't track any other factors related to dropout rates. The e-Tracker is an excellent tool for measuring real coverage and should be scaled nationwide. Funding: UNICEF, Bangladesh.

Use of volar distal radius plate dorsally for wrist arthrodesis in patients with upper limb spasticity: A retrospective review.

Standard wrist arthrodesis implants are generally designed for adult joints with arthritis. They are often too big for patients with limb spasticity who generally tend to have osteopenic and smaller bones for their age, resulting in high complication rates. We previously described the novel use of volar distal radius variable-angle locking plate (APTUS® Wrist distal radius system 2.5, Medartis AG, Basel, Switzerland) on the dorsum for wrist arthrodesis in patients with limb spasticity. This study aimed to further establish the use of the implant by reporting the outcomes in cohort A (nondistal radius plate) and cohort B (distal radius plate cohort). Patient-reported outcome measures were used to assess the primary outcome, whereas secondary outcomes included implant-related complications and improvement in wrist position and fusion rates. A total of 17 wrist arthrodesis procedures were performed over a period of 4 years in 15 patients for wrist deformity secondary to limb spasticity. There were no complaints of implant prominence, implant or tendon irritation, metacarpal prominence, or extension requiring further treatment in cohort B. Cohort A had a high implant removal rate that is comparable to the published literature. Both groups reported significant improvement in hygiene and wrist position but neither group had any appreciable gain in function. Volar distal radius variable-angle locking plates appear to be safe and have superior patient acceptability and low complication rates when used dorsally for wrist arthrodesis in patients with upper limb spasticity. Comparable overall satisfaction rates in cohort B were reported in relation to the literature and the cohort A in this study.

Stacking Cyclophanes into Chiral Microvessels.

Engineering novel micro-/nanoscale systems and devices based on supramolecular assembly has tremendous potential from diverse applications perspective. However, controlling the size, shape, spatial arrangements, and hierarchical transcription by a dimensional organizing principle (1D-3D arrangement) without the help of templates remains a challenging task. In this vein, a recent study by Oki and colleagues reporting the stacking of chiral cyclophanes via intermolecular non-covalent interactions for crafting synchronous microcrystalline 3D chiral vessels with controlled conformational arrangements represents a truly remarkable illustration of molecular engineering. The microvessels bear stereocontrolled skeletal morphology, recognize stereoisomers and serve as containers to accommodate microcrystals, polymer particles, and fluorescent dyes. The full application scope of this fascinating research is far beyond non-covalent interactions, supramolecular self-assembly, and crystal engineering.

Synthesis of Non-centrosymmetric Dipolar 4,4'-Bipyridines: Potential Molecular Tectons for Programmed Assembly of Supramolecular Systems.

In this report, we describe a modular synthesis approach towards a new series of non-centrosymmetric, dipolar 4,4'-bipyridines bearing 2,6- and 3,5-functionalized pyridyl moieties at the peripheries. Central to our strategy is the selective substitution on only one pyridyl motif that could contain electron-donating (-CH3 ) or electron-withdrawing (-F, -Cl, -CF3 ) groups which causes electronic/steric effects on one nitrogen atom in 4,4'-bipyridines. This synthetic protocol was further applied to prepare azo-functionalized (-N=N-) asymmetric bipyridines and non-centrosymmetric 4,4'-bipyridine N-oxide scaffolds, which overcome the synthetic hurdles oxidizing 4,4'-bipyridines to N-monoxides selectively at only one pyridine. Compared to the conventional symmetrical bipyridines, the dipolar non-centrosymmetric molecular tectons pave the way for the realization of non-centrosymmetric supramolecular assemblies because of the difference in the binding energy of the pyridyl nitrogen atoms.

Design Strategies for Structurally Controlled Polymer Surfaces via Cyclophane-Based CVD Polymerization and Post-CVD Fabrication.

Molecular structuring of soft matter with precise arrangements over multiple hierarchical levels, especially on polymer surfaces, and enabling their post-synthetic modulation has tremendous potential for application in molecular engineering and interfacial science. Here, recent research and developments in design strategies for structurally controlled polymer surfaces via cyclophane-based chemical vapor deposition (CVD) polymerization with precise control over chemical functionalities and post-CVD fabrication via orthogonal surface functionalization that facilitates the formation of designable biointerfaces are summarized. Particular discussion about innovative approaches for the templated synthesis of shape-controlled CVD polymers, ranging from 1D to 3D architecture, including inside confined nanochannels, nanofibers/nanowires synthesis into an anisotropic media such as liquid crystals, and CVD polymer nanohelices via hierarchical chirality transfer across multiple length scales is provided. Aiming at multifunctional polymer surfaces via CVD copolymerization of multiple precursors, the structural and functional design of the fundamental [2.2]paracyclophane (PCP) precursor molecules, that is, functional CVD monomer chemistry is also described. Technologically advanced and innovative surface deposition techniques toward topological micro- and nanostructuring, including microcontact printing, photopatterning, photomask, and lithographic techniques such as dip-pen nanolithography, showcasing research from the authors' laboratories as well as other's relevant important findings in this evolving field are highlighted that have introduced new programmable CVD polymerization capabilities. Perspectives, current limitations, and future considerations are provided.

Tumour necrosis factor-α -308G/A polymorphism is associated with insulin secretory defects in Bangladeshi prediabetic/diabetic subjects.

Objectives: Tumour necrosis factor (TNF)-α, an adipocytokine, is closely linked to impaired glucose tolerance (IGT) and insulin resistance (IR) in type 2 diabetes (T2D) subjects. The relationship between the polymorphisms in the TNF-α gene and IR in Bangladeshi prediabetes and T2D subjects has not yet been fully identified. This study aims to reveal the association between TNF-α gene polymorphism and IR in hyperglycaemic patients of Bangladeshi origin. Methods: In our study, 106 IGT, 100 T2D, and 109 healthy subjects of Bangladeshi origin were recruited to identify the impact of TNF-α gene polymorphism at position -308 with a G>A transition using PCR and subsequent restriction fragment length polymorphism (RFLP). Results: The -308G>A TNF-α genotype frequency distribution within the control, IGT, and T2D groups showed a significant association (χ2 = 21.077; P = 0.001), although allele frequency distribution within the groups showed a statistically non-significant difference (χ2 = 1.696; P = 0.091). ß-cell functional deficiency (HOMA-B%) was observed to be significantly (P = 0.034) lower in subjects with a variant genotype. In addition, our results indicate that the study subjects' body mass index (BMI) and residence status were positively correlated (P ≤ 0.05) with -308G>A TNF-α gene polymorphism. Conclusions: Therefore, it can be concluded that -308G>A TNF-α gene polymorphism may have a causative relationship with lower insulin secretory capacity and higher BMI in Bangladeshi IGT and T2D populations, while the urban population's lifestyle might be associated with this polymorphism.

C-P bond formation of cyclophanyl-, and aryl halides via a UV-induced photo Arbuzov reaction: a versatile portal to phosphonate-grafted scaffolds.

A new versatile method for the C-P bond formation of (hetero)aryl halides with trimethyl phosphite via a UV-induced photo-Arbuzov reaction, accessing diverse phosphonate-grafted arenes, heteroarenes and co-facially stacked cyclophanes under mild reaction conditions without the need for catalyst, additives, or base is developed. The UV-induced photo-Arbuzov protocol has a wide synthetic scope with large functional group compatibility exemplified by over 30 derivatives. Besides mono-phosphonates, di- and tri-phosphonates are accessible in good to excellent yields. Mild and transition metal-free reaction conditions consolidate this method's potential for synthesizing pharmaceutically relevant compounds and precursors of supramolecular nanostructured materials.

Babies of South Asian and European Ancestry Show Similar Associations With Genetic Risk Score for Birth Weight Despite the Smaller Size of South Asian Newborns.

Size at birth is known to be influenced by various fetal and maternal factors, including genetic effects. South Asians have a high burden of low birth weight and cardiometabolic diseases, yet studies of common genetic variations underpinning these phenotypes are lacking. We generated independent, weighted fetal genetic scores (fGSs) and maternal genetic scores (mGSs) from 196 birth weight-associated variants identified in Europeans and conducted an association analysis with various fetal birth parameters and anthropometric and cardiometabolic traits measured at different follow-up stages (5-6-year intervals) from seven Indian and Bangladeshi cohorts of South Asian ancestry. The results from these cohorts were compared with South Asians in UK Biobank and the Exeter Family Study of Childhood Health, a European ancestry cohort. Birth weight increased by 50.7 g and 33.6 g per SD of fGS (P = 9.1 × 10-11) and mGS (P = 0.003), respectively, in South Asians. A relatively weaker mGS effect compared with Europeans indicates possible different intrauterine exposures between Europeans and South Asians. Birth weight was strongly associated with body size in both childhood and adolescence (P = 3 × 10-5 to 1.9 × 10-51); however, fGS was associated with body size in childhood only (P < 0.01) and with head circumference, fasting glucose, and triglycerides in adults (P < 0.01). The substantially smaller newborn size in South Asians with comparable fetal genetic effect to Europeans on birth weight suggests a significant role of factors related to fetal growth that were not captured by the present genetic scores. These factors may include different environmental exposures, maternal body size, health and nutritional status, etc. Persistent influence of genetic loci on size at birth and adult metabolic syndrome in our study supports a common genetic mechanism that partly explains associations between early development and later cardiometabolic health in various populations, despite marked differences in phenotypic and environmental factors in South Asians.

Diversity-Oriented Synthesis of [2.2]Paracyclophane-derived Fused Imidazo[1,2-a]heterocycles by Groebke-Blackburn-Bienaymé Reaction: Accessing Cyclophanyl Imidazole Ligands Library.

This report describes the synthesis of a [2.2]paracyclophane-derived annulated 3-amino-imidazole ligand library through a Groebke-Blackburn-Bienaymé three-component reaction (GBB-3CR) approach employing formyl-cyclophanes in combination with diverse aliphatic and aromatic isocyanides and heteroaromatic amidines. The GBB-3CR process gives access to skeletally-diverse cyclophanyl imidazole ligands, namely 3-amino-imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrazines. Additionally, a one-pot protocol for the GBB-3CR by an in situ generation of cyclophanyl isocyanide is demonstrated. The products were analyzed by detailed spectroscopic techniques, and the cyclophanyl imidazo[1,2-a]pyridine was confirmed unambiguously by single-crystal X-Ray crystallography. The cyclophanyl imidazole ligands can be readily transformed to showcase their useful utility in preparing N,C-palladacycles through regioselective ortho-palladation.

Metal-to-Metal Distance Modulated Au(I)/Ru(II) Cyclophanyl Complexes: Cooperative Effects in Photoredox Catalysis.

The modular synthesis of Au(I)/Ru(II) decorated mono- and heterobimetallic complexes with π-conjugated [2.2]paracyclophane is described. [2.2]Paracyclophane serves as a rigid spacer which holds the metal centers in precise spatial orientations and allows metal-to-metal distance modulation. A broad set of architectural arrangements of pseudo -geminal, -ortho, -meta, and -para substitution patterns were employed. Metal-to-metal distance modulation of Au(I)/Ru(II) heterobimetallic complexes and the innate transannular π-communication of the cyclophanyl scaffold provides a promising platform for the investigations of structure-activity relationship and cooperative effects. The Au(I)/Ru(II) heterobimetallic cyclophanyl complexes are stable, easily accessible, and exhibit promising catalytic activity in the visible-light promoted arylative Meyer-Schuster rearrangement.

Metal-to-Metal Distance Modulation by Ligand Design: A Case Study of Structure-Property Correlation in Planar Chiral Cyclophanyl Metal Complexes.

Multinuclear metal complexes have seen tremendous progress in synthetic advances, their versatile structural features, and emerging applications. Here, we conceptualize Metal-to-Metal distance modulation in cyclophanyl metal complexes by bridging ligand design employing the co-facially stacked cyclophanyl-derived pseudo-geminal, -ortho, -meta, and -para constitutional isomers grafted with N-, O-, and P- containing chelates that allow the installation of diverse (hetero)metallic moieties in a distance-defined and spatially-oriented relation to one another. Metal-to-Metal distance modulation and innate transannular "through-space" π-π electronic interactions via the co-facially stacked benzene rings in cyclophanyl-derived complexes as well as their specific stereochemical structural features (element of planar chirality) are crucial factors that contribute to the tuning of structure-property relationships, which stand at the very center from the perspective of cooperative effects in catalysis as well as emerging material applications.

Molecular Design and Synthesis of Dicarbazolophane-Based Centrosymmetric Through-Space Donors for Solution-Processed Thermally Activated Delayed Fluorescence OLEDs.

Conjugation-extended carbazolophane donors, dicarbazolophanes (DCzp), were designed and synthesized using a multifold stepwise Pd-catalyzed Buchwald-Hartwig amination/ring cyclization process. Furthermore, elaboration of the DCzp core is possible with the introduction of pendant carbazole derivative groups. This provides a way to tune the optoelectronic properties of the thermally activated delayed fluorescence (TADF) compounds DCzpTRZtBu, dtBuCzDCzpTRZtBu, and dMeOCzDCzpTRZtBu. Solution-processed organic light-emitting diodes (OLEDs) were fabricated and achieved a maximum external quantum efficiency (EQEmax) of 8.2% and an EQE of 7.9% at 100 cd/m2.

Vitamin D3 and B12 supplementation in pregnancy.

AIM: To assess the efficacy of vitamin D3 or B12 supplementation during pregnancy. METHODS: Pregnant women at 6-14 weeks in the intervention arm received oral high dose intermittent vitamin D3 and/or low dose B12 supplementation if they had vitamin D or vitamin B12 deficiency. The control arm received prescribed dietary instruction only. An additional observational arm for those mothers at booking with normal vitamin D and vitamin B12 level was also recruited. All groups received standard care during pregnancy. RESULTS: The primary endpoint of either vitamin D or B12 at term was not met. At baseline 25% participants in both the interventional and control arms had severe D deficiency (<30 nmol/l), reducing to under 3.4% in both groups. No maternal differences in vitamin D or B12 levels were found at delivery between the intervention, control, or observational groups. No significant difference in any of the pregnancy or birth outcomes was observed between three groups. CONCLUSIONS: In this study, oral supplementation of high dose intermittent vitamin D or low dose vitamin B12 regime failed to correct the relevant nutritional deficiencies in Bangladeshi pregnant women as per protocol. Both dietary supplementation and high dose vitamin D corrected severe vitamin deficiency.

IgG antibody response demonstrates inverse correlation with viral load in Bangladeshi women with acute hepatitis E virus genotype 1 infection.

OBJECTIVES: To determine IgG immune responses and hepatitis E virus (HEV) viral load, and to explore the associations with pregnancy. METHODS: A total of 121 HEV-infected women (57 pregnant, 64 non-pregnant) were analysed. Quantitative reverse transcription PCR (RT-qPCR) was done for 78 HEV IgM-positive patients to determine viral load, and Sanger sequencing was performed for 62 HEV-RNA-positive patients to confirm genotyping. ELISA was conducted to determine HEV antibody and avidity indices. RESULTS: The HEV genotype was identified as variant 1. Significant negative correlations were observed between log HEV copy number and log hepatitis E virus IgG antibody index in the late acute phase of jaundice for both pregnant women (r = -0.7971, p = 0.0002) and non-pregnant women (r = -0.9117, p = 0.0002). Pregnant women had significantly higher serum log viral copy numbers and lower IgG antibody indices than non-pregnant women in the late acute phase of HEV-induced jaundice (p = 0.0196 and p = 0.0303, respectively). Moreover, pregnant women with acute HEV hepatitis had higher cross-reactive IgG antibodies compared to the non-pregnant women (p = 0.0017). Five patients with HEV hepatitis died, of whom four were pregnant. CONCLUSIONS: Pregnancy might be associated with higher viral loads and a lower IgG response in the HEV-induced late acute phase of jaundice.

Criegee Intermediates Beyond Ozonolysis: Synthetic and Mechanistic Insights.

After more than 70 years since their discovery, Criegee intermediates (CIs) are back at the forefront of modern chemistry of short-lived reactive intermediates. They play an important role in the mechanistic context of chemical synthesis, total synthesis, pharmaceuticals, and, most importantly, climate-controlling aerosol formation as well as atmospheric chemistry. This Minireview summarizes key aspects of CIs (from the mechanism of formation, for example, by ozonolysis of alkenes and photolysis methods employing diiodo and diazo compounds, to their electronic structures and chemical reactivity), highlights the most recent findings and some landmark results of gas-phase kinetics, and detection/measurements. The recent progress in synthetic and mechanistic studies in the chemistry of CIs provides a guide to illustrate the possibilities for further investigations in this exciting field.

OBO-Fused Benzo[fg]tetracene as Acceptor With Potential for Thermally Activated Delayed Fluorescence Emitters.

Six luminophores bearing an OBO-fused benzo[fg]tetracene core as an electron acceptor were designed and synthesized. The molecular structures of three molecules (PXZ-OBO, 5PXZ-OBO, 5DMAC-OBO) were determined by single crystal X-ray diffraction studies and revealed significant torsion between the donor moieties and the OBO acceptor with dihedral angles between 75.5 and 86.2°. Photophysical studies demonstrate that blue and deep blue emission can be realized with photoluminescence maxima (λPL) ranging from 415 to 480 nm in mCP films. The emission energy is modulated by simply varying the strength of the donor heterocycle, the number of donors, and their position relative to the acceptor. Although the DMAC derivatives show negligible delayed emission because of their large singlet-triplet excited state energy difference, ΔE ST, PXZ-based molecules, especially PXZ-OBO with an experimental ΔE ST of 0.25 eV, demonstrate delayed emission in blend mCP films at room temperature, which suggests triplet exciton harvesting occurs in these samples, potentially by thermally activated delayed fluorescence.