Exercise and QUality diet After Leukemia (EQUAL): A randomized weight loss trial among adult survivors of childhood leukemia in the Childhood Cancer Survivor Study.

BACKGROUND: Obesity is prevalent in childhood cancer survivors and interacts with cancer treatments to potentiate risk for cardiovascular (CV) death. We tested a remote weight-loss intervention that was effective among adults with CV risk factors in a cohort of adult survivors of childhood acute lymphoblastic leukemia (ALL) with overweight/obesity. METHODS: In this phase 3 efficacy trial, survivors of ALL enrolled in the Childhood Cancer Survivor Study with body mass index (BMI)≥25 kg/m2 were randomized to a remotely-delivered weight-loss intervention versus self-directed weight loss, stratified by history of cranial radiotherapy (CRT). The primary endpoint was the difference in weight loss at 24-months in an intent-to-treat analysis. Analyses were performed using linear mixed effects models. RESULTS: Among 358 survivors (59% female, median attained age: 37 years, IQR: 33-43), baseline mean (SD) weight was 98.6 kg (24.0) for the intervention group (n=181) and 94.9 kg (20.3) for controls (n=177). Adherence to the intervention was poor; 15% of individuals in the intervention completed 24/30 planned coaching calls. Weight at 24-months was available for 274 (77%) participants. After controlling for CRT, sex, race/ethnicity, and age, the mean (SE) change in weight from baseline to 24-months was -0.4 kg (0.8) for intervention and 0.2 kg (0.6) for control participants (p=0.59). CONCLUSIONS: A remote weight-loss intervention that was successful among adults with CV conditions did not result in significant weight loss among adult survivors of childhood ALL. IMPACT: Future interventions in this population must be tailored to the unique needs of survivors to encourage engagement and adherence.

Glutamic Acid Modified Gold Nanorod Sensor for the Detection of Calcium ions in Neuronal Cells.

Calcium (Ca2+) ions play a crucial role in the functioning of neurons, governing various aspects of neuronal activity such as rapid modulation and alterations in gene expression. Ca2+ signaling has a significant impact on the development of diseases and the impairment of neuronal functions. Herein, the study reports a Ca2+ ion sensor in neuronal cells using a gold nanorod. The gold nanorod (GA-GNR) conjugated glutamic acid developed in the study was used as a nano-bio probe for the experimental and in vitro detection of calcium. The nanosensor is colloidally stable, preserves plasmonic properties, and shows good viability in neuronal cells, as well as promoting neuron cell line growth. The cytotoxicity and cell penetration of the nanosensor are studied using Raman spectroscopy, brightfield and darkfield microscopy imaging, and MTT assays. The quantification of Ca2+ ions in neuronal cells is determined by monitoring the surface plasmon resonance (SPR) of the GA-GNR. The change in the intensity profile in the presence of Ca2+ incubated neurons was effectively used to develop a portable prototype of an optical Ca2+ sensor, proposing it as a tool for neurodegenerative disease diagnosis and neuromodulation evaluation.

Nuclease-free precise genome editing corrects MECP2 mutations associated with Rett syndrome.

Rett syndrome is an acquired progressive neurodevelopmental disorder caused by de novo mutations in the X-linked MECP2 gene which encodes a pleiotropic protein that functions as a global transcriptional regulator and a chromatin modifier. Rett syndrome predominantly affects heterozygous females while affected male hemizygotes rarely survive. Gene therapy of Rett syndrome has proven challenging due to a requirement for stringent regulation of expression with either over- or under-expression being toxic. Ectopic expression of MECP2 in conjunction with regulatory miRNA target sequences has achieved some success, but the durability of this approach remains unknown. Here we evaluated a nuclease-free homologous recombination (HR)-based genome editing strategy to correct mutations in the MECP2 gene. The stem cell-derived AAVHSCs have previously been shown to mediate seamless and precise HR-based genome editing. We tested the ability of HR-based genome editing to correct pathogenic mutations in Exons 3 and 4 of the MECP2 gene and restore the wild type sequence while preserving all native genomic regulatory elements associated with MECP2 expression, thus potentially addressing a significant issue in gene therapy for Rett syndrome. Moreover, since the mutations are edited directly at the level of the genome, the corrections are expected to be durable with progeny cells inheriting the edited gene. The AAVHSC MECP2 editing vector was designed to be fully homologous to the target MECP2 region and to insert a promoterless Venus reporter at the end of Exon 4. Evaluation of AAVHSC editing in a panel of Rett cell lines bearing mutations in Exons 3 and 4 demonstrated successful correction and rescue of expression of the edited MECP2 gene. Sequence analysis of edited Rett cells revealed successful and accurate correction of mutations in both Exons 3 and 4 and permitted mapping of HR crossover events. Successful correction was observed only when the mutations were flanked at both the 5' and 3' ends by crossover events, but not when both crossovers occurred either exclusively upstream or downstream of the mutation. Importantly, we concluded that pathogenic mutations were successfully corrected in every Rett line analyzed, demonstrating the therapeutic potential of HR-based genome editing.

Copper perchlorate catalyzed oxidative cyclisation of a novel bishydrazone ligand, formation of an unusual copper complex and in vitro biological implications.

A novel hexadentate bishydrazone ligand, 1,10-bis(di(2-pyridyl)ketone) adipic acid dihydrazone (H2L1) is synthesized and characterized. With copper perchlorate as a catalytic oxidant, the ligand undergoes oxidative cyclisation and resulted in the formation of an unusual copper complex [Cu(L1a)2Cl]ClO4 (1), where L1a is 3-(2-pyridyl)triazolo[1,5-a]-pyridine. The Cu(II) complex was characterized physicochemically, while the molecular structure was confirmed by single crystal X- ray diffraction. In the complex cation, copper(II) is in a distorted trigonal bipyramidal coordination environment, surrounded by two triazolo nitrogen atoms and two pyridyl nitrogen atoms of L1a and a chloride atom. The relevant non covalent intermolecular interactions of the complex quantified using Hirshfeld surface analysis reveals that the O···H/ H···O (27.2%) contacts has the highest contribution. The solution phase bandgaps of the compounds were calculated using Tauc plot, whereas the solid-state band gaps were calculated by Kubelka-Munk model. DFT studies of the compounds indicate that the theoretical calculations corroborate with the experimental data. DPPH antioxidant activity assay of the synthesized compounds showed that the proligand H2L1 has a lower IC50 value (24.1 µM) than that of complex 1 (29.7 µM). The in vitro antibacterial activity was evaluated against Escherichia coli and Staphylococcus aureus, which revealed that complex 1 have excellent activity against E. coli, much as the standard ciprofloxacin. The cytotoxic efficacy investigation of the compounds against A549 (lung) adenocarcinoma cells suggested that H2L1 has more anticancer activity (IC50 value of 149.08 µM) than that of complex 1(IC50 value of 176.70 µM).

Uterine washings as a novel method for early detection of ovarian cancer: Trials and tribulations.

Given the tubal origin of high-grade serous ovarian cancer (HGSC), we sought to investigate intrauterine lavage (IUL) as a novel method of biomarker detection. IUL and serum samples were collected from patients with HGSC or benign pathology. Although CA-125 and HE4 concentrations were significantly higher in IUL samples compared to serum, they were similar between IUL samples from patients with HGSC vs benign conditions. In contrast, CA-125 and HE4 serum concentrations differed between HGSC and benign pathology (P =.002 for both). IUL and tumor samples from patients with HGSC were subjected to targeted panel sequencing and droplet digital PCR (ddPCR). Tumor mutations were found in 75 % of matched IUL samples. Serum CA-125 and HE4 biomarker levels allowed for better differentiation of HGSC and benign pathology compared to IUL samples. We believe using IUL for early detection of HGSC requires optimization, and current strategies should focus on prevention until early detection strategies improve.

Investigating the Current Harmonization Status of Tumor Markers Using Global External Quality Assessment Programs: A Feasibility Study.

BACKGROUND: The harmonization status of most tumor markers (TMs) is unknown. We report a feasibility study performed to determine whether external quality assessment (EQA) programs can be used to obtain insights into the current harmonization status of the tumor markers α-fetoprotein (AFP), prostate specific antigen (PSA), carcinoembryonic antigen (CEA), cancer antigen (CA)125, CA15-3 and CA19-9. METHODS: EQA sample results provided by 6 EQA providers (INSTAND [Germany], Korean Association of External Quality Assessment Service [KEQAS, South Korea], National Center for Clinical Laboratories [NCCL, China], United Kingdom National External Quality Assessment Service [UK NEQAS, United Kingdom], Stichting Kwaliteitsbewaking Medische Laboratoriumdiagnostiek [SKML, the Netherlands], and the Royal College of Pathologists of Australasia Quality Assurance Programs [RCPAQAP, Australia]) between 2020 and 2021 were used. The consensus means, calculated from the measurement procedures present in all EQA programs (Abbott Alinity, Beckman Coulter DxI, Roche Cobas, and Siemens Atellica), was used as reference values. Per measurement procedure, the relative difference between consensus mean for each EQA sample and the mean of all patient-pool-based EQA samples were calculated and compared to minimum, desirable, and optimal allowable bias criteria based on biological variation. RESULTS: Between 19040 (CA15-3) and 25398 (PSA) individual results and 56 (PSA) to 76 (AFP) unique EQA samples were included in the final analysis. The mean differences with the consensus mean of patient-pool-based EQA samples for all measurement procedures were within the optimum bias criterion for AFP, the desirable bias for PSA, and the minimum bias criterion for CEA. However, CEA results <8 µg/L exceeded the minimum bias criterion. For CA125, CA15-3, and CA19-9, the harmonization status was outside the minimum bias criterion, with systematic differences identified. CONCLUSIONS: This study provides relevant information about the current harmonization status of 6 tumor markers. A pilot harmonization investigation for CEA, CA125, CA15-3, and CA19-9 would be desirable.

Porphyrin and doxorubicin mediated nanoarchitectonics of copper clusters: a bimodal theranostics for cancer diagnosis and treatment in vitro.

Nanoarchitectonics, an emerging strategy, presents a promising alternative for developing highly efficient next-generation functional materials. Multifunctional materials developed using nanoarchitectonics help to mimic biological molecules. Porphyrin-based molecules can be effectively utilized to design such assemblies. Metal nanocluster is one of the functional materials that can shed more insight into developing nanoarchitectonic materials. Herein, an inherently near-infrared (NIR) fluorescing copper nanocluster (CuC)-mediated structural assembly via protoporphyrin IX (PPIX) and doxorubicin (Dox) is demonstrated as the functional material. Dox-loaded porphyrin-mediated CuC assembly shows singlet oxygen generation and 66% drug release at 15 min. Furthermore, the efficacy of this material is tested for cancer diagnosis and bimodal therapeutic strategy due to the fluorescing ability of the cluster and loading of PPIX as well as the drug, respectively. The nanoarchitecture exhibits targeted imaging and 83% cell death in HeLa cells upon laser irradiation with 10 nmoles and 20 nmoles of PPIX and Dox, respectively.

Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis.

Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late-stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes-rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles-rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early-stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late-stage PDAC patients undergoing chemotherapy, lower GPC1 tMV-mProtein and Exo-mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis.

Hyperspectral dataset of pure and pesticide-coated apples for measuring the level of fertilizers used.

This dataset provides three classes of hyperspectral images: pure, insecticide-immersed, and fungicide-immersed apples with different concentrations of fertilizers. The hyperspectral images were calibrated under white and dark correction and enhanced using contrast enhancement. In order to know the variations in the level of fertilizers used, we soaked the apples in 2 different concentrations of chemicals i.e., 1ml or 1g of fertilizer in 1 liter of water as low concentration, and 3ml or 3g of fertilizer in 1 liter of water as high concentration. The proposed dataset will help in finding the consumption level of fertilizers (pesticides) in apples.

Rift valley fever (RVF) viral zoonotic disease steadily circulates in the Mauritanian animals and humans: A narrative review.

Background and Aim: Rift valley fever (RVF) virus (RVFV) is reportedly steadily circulating in Mauritania being repeated in 1987, 2010, 2012, 2015, and 2020. Mauritania seems a preferred niche for RVF virus due to its persistent outbreak there. Lately, nine Mauritanian wilayas confirmed 47 (23 fatalities with 49% CFR) human cases between August 30 and October 17, 2022. Most of the cases were largely among livestock breeders associated with animal husbandry activities. The review aimed at understanding the origin, cause, and measures to counter the virus. Methods: The facts and figures from the various published articles sourced from databases including Pubmed, Web of Science, and the Scopus as also some primary data from health agencies like WHO, CDC, and so forth were evaluated and the efficacy of countermeasures reviewed. Results: Among the reported confirmed cases, it was found that 3-70 year age-group males outnumbered the females. Deaths after fever occurred primarily due to acute hemorrhagic thrombocytopenia. Human infections often occurred through zoonotic transmission mainly through mosquitoes in the population contiguous to cattle outbreak, a conducive site for local RVFV transmission. Many transmission cases were through direct or indirect contact with blood or organs of the infected animal. Conclusion: RVFV infection was predominant in the Mauritanian regions bordering Mali, Senegal, and Algeria. High human and domesticated animal density as also the existing zoonotic vectors further contributed to RVF virus circulation. Mauritanian RVF infection data confirmed that RVFV was zoonotic that included small ruminants, cattle, and camel. This observation hints at the role of transborder animal mobility in RVFV transmission. In light of this, preventive approaches with effective surveillance and monitoring system following the One Health model is extremely beneficial for a free and fair healthy world for all.

Correction: An insight into the optical properties of a sub nanosize glutathione stabilized gold cluster.

Correction for 'An insight into the optical properties of a sub nanosize glutathione stabilized gold cluster' by Lakshmi V. Nair et al., Dalton Trans., 2016, 45, 11286-11291, https://doi.org/10.1039/C6DT01753C.

Hormonal therapies in females with blood disorders: thrombophilia, thrombosis, hemoglobinopathies, and anemias.

There is widespread use of gonadal steroid hormone therapy for a variety of indications throughout the reproductive and postreproductive lifespan. These therapies may have particular benefits and specific risk among those with blood disorders, including inherited or acquired bleeding disorders, thrombophilia, thrombosis, or anemia. This clinical review is intended to provide a guidance for counseling and management of adolescent and adult biologic females with thrombophilic risk factors and/or thrombosis who require hormonal therapy. In general, synthetic estrogens present in contraceptive products should be avoided in those with a personal or strong family history of thrombosis or thrombophilias. In contrast, natural estrogens present in formulations for climacteric symptom management do not need to be avoided, and vaginal or transdermal formulations are preferred. Likewise, transdermal estradiol is preferred for gender-affirming hormone therapy and requires individualized assessment in those at high risk of thrombosis. Progestogens (either synthetic progestins or naturally occurring progesterone) can be used safely in nearly all patients. There is minimal safety evidence among anticoagulated patients at risk for thrombosis, which requires a patient-specific approach when discussing hormone therapies.

Anti-bacterial activity of Cymbopogon citratus nanoparticles against Vibrio species infecting aquatic organisms.

The presence of Vibrio parahaemolyticus, Vibrio alginolyticus, and Vibrio harveyi in aquatic organisms causes vibriosis, leading to their significant mortality. The efficacy of antibiotic treatment is reduced due to increasing antibiotic resistance. As a result, novel therapeutic agents are increasingly needed to treat outbreak of such diseases in aquatic organisms and humans. This study focuses on utilizing the bioactive compounds of Cymbopogon citratus as they are rich in a variety of secondary metabolites which promotes growth, natural immune response and disease resistance against pathogenic bacteria in various ecosystems. In silico studies were performed to evaluate the binding potential of the bioactive compounds against targeted protein beta - lactamase in Vibrio parahaemolyticus and metallo - beta - lactamase in V. alginolyticus via molecular docking. Cymbopogon citratus nanoparticles (CcNps) were synthesized, characterized and toxicity studies were performed by using Vigna radiata, and Artemia nauplii at different concentrations of Cymbopogon citratus nanoparticles. The results revealed that the synthesized nanoparticles were non-ecotoxic and act as potential growth promoters in plants. The antibacterial activity of synthesized Cymbopogon citratus was evaluated using agar well diffusion method. MIC, MBC, and biofilm assays performed by using different concentrations of synthesized nanoparticles. Thus, it was proved that Cymbopogon citratus nanoparticles showed better antibacterial activity against Vibrio species.

Six-month follow-up of salivary antioxidant defense outcomes of individuals using medicated toothpaste.

Objective: The objective of this study was to study the effect of medicated toothpaste on oral health, a 6-month follow-up. Methods: Four hundred and twenty-seven participants were screened and followed up for 6 months. The intraoral examination was performed to record caries, gingival bleeding, and plaque index. Saliva collected was evaluated for pH, total antioxidant capacity (TAC), malondialdehyde (MDA), and Vitamin C level for 6 months, and data were analyzed. Results: On the usage of medicated toothpaste with herbal extract for 6 months, the salivary pH levels were increased, the interquartile range for plaque, and the gingival bleeding index decreased. The percentage change in salivary TAC, MDA, and Vitamin C levels in the caries-free group of subgroup I was 174.8, 58.06, and 59.98, respectively, in subgroup II was 133.3, 52.08, and 58.51, and in subgroup III was 63.77, 45.11, and 47.77. The percentage change in salivary TAC, MDA, and Vitamin C levels in the caries-active group of subgroup I was 136.62, 57.27, and 72.83, subgroup II was 108.59, 37.50, and 61.55, and in subgroup III was 35.62, 30.82, and 54.10, respectively. Conclusion: The salivary pH levels increased on the usage of medicated toothpaste with herbal extract; plaque and the gingival bleeding index scores were decreased. The salivary antioxidant defense was increased in individuals using medicated toothpaste with herbal extracts which signifies an improvement in overall oral health in the 6-month follow-up.

Management of paediatric ankylosis.

Temporomandibular joint ankylosis (TMJa) is one of the most crippling craniomaxillofacial pathological conditions characterized by replacement of normal architecture of temporomandibular joint (TMJ) with fibrous or bony tissue. The incidence of TMJa is most common in the paediatric population [first and second decades of life] and is commonly associated with maxillofacial trauma. Comprehensive management entails a thorough evaluation of the associated anatomy of the ankylotic mass and other pertinent details like the presence or absence of obstructive sleep apnoea. Categorizing patients based on these variables helps in selecting an appropriate surgical intervention. Various resective and reconstructive surgical techniques are discussed; along with their merits and demerits. Long-term physiotherapy, long-term clinical follow-up and appropriate family counselling are the essential pillars for success. In this review, the authors present an algorithmic approach to evaluation and management of paediatric TMJa. Appropriate recommendations are made based on evidence to select optimum surgical intervention.