Search

Purpose: Normative ADC values of the pineal gland in young children are currently lacking, however, these are potentially useful in the differential diagnosis of pineal involvement in trilateral retinoblastoma, which is challenging when the size of the tumor is less than 10-15 mm. The main objective of this study was to establish ADC reference values of the normal pineal gland in a large cohort of children between 0 and 4 years., Methods: This retrospective study was conducted in a tertiary pediatric hospital. We collected 64 patients with normal MRI examination (between 2017 and 2024) and clinical indication unrelated to the pineal gland, and divided them into 5 age groups (0 to 4 years). Gland size and mean ADC values were calculated, using the ellipsoid formula and ROI/histogram analysis, respectively. The established values were tested in three cases of trilateral retinoblastoma (10 to 20 months)., Results: Mean ADC values were always above 1000 × 10 - 6 mm 2 /s, while in patients with trilateral retinoblastoma they were around 800 × 10 - 6 mm 2 /s. Pineal ADC values were identical in both genders. The volume of the pineal gland showed a tendency to increase with age., Conclusions: We present ADC reference data for the pineal gland in children under 4 years of age. The distribution of mean ADC values of trilateral retinoblastoma was significantly different from the normative values, hence, the use DWI/ADC may help to identify small trilateral retinoblastoma in children with ocular pathology., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Purpose: Sotos syndrome is a rare autosomal dominant condition caused by pathogenic mutations in the NSD1 gene that presents with craniofacial dysmorphism, overgrowth, seizures, and neurodevelopmental delay. Macrocephaly, ventriculomegaly, and corpus callosal dysmorphism are typical neuroimaging features that have been described in the medical literature. The purpose of this study was to expand on the neuroimaging phenotype by detailed analysis of a large cohort of patients with genetically proved Sotos syndrome., Materials and Methods: This multicenter, multinational, retrospective observational cohort study systematically analyzed the clinical characteristics and neuroimaging features of 77 individuals with genetically diagnosed Sotos syndrome, via central consensus review with 3 pediatric neuroradiologists., Results: In addition to previously described features, malformations of cortical development were identified in most patients (95.0%), typically dysgyria (92.2%) and polymicrogyria (22.1%), varying in location and distribution. Incomplete rotation of the hippocampus was observed in 50.6% of patients and was associated with other imaging findings, in particular with dysgyria (100% versus 84.2%, P  = .012)., Conclusions: Our findings show a link between the genetic-biochemical basis and the neuroimaging features and aid in better understanding the underlying clinical manifestations and possible treatment options. These findings have yet to be described to this extent and correspond with recent studies that show that NSD1 participates in brain development and has interactions with other known relevant genetic pathways., (© 2024 by American Journal of Neuroradiology.)

Introduction: Canavan disease (CD) is a rare autosomal recessive neurodegenerative disorder caused by a deficiency of aspartoacylase A, an enzyme that degrades N-acetylaspartate (NAA). The disease is characterized by progressive white matter degeneration, leading to intellectual disability, seizures, and death. This retrospective study aims to describe the full spectrum of magnetic resonance imaging (MRI) findings in a large case series of CD patients., Materials and Methods: MRI findings in 18 patients with confirmed CD were investigated, and the full spectrum of brain abnormalities was compared with the existing literature to provide new insights regarding the brain MRI findings in these patients. All the cases were proven based on genetic study or NAA evaluation in urine or brain., Results: Imaging analysis showed involvement of the deep and subcortical white matter as well as the globus pallidus in all cases, with sparing of the putamen, caudate, and claustrum. The study provides updates on the imaging characteristics of CD and validates some underreported findings such as the involvement of the lateral thalamus with sparing of the pulvinar, involvement of the internal capsules and corpus callosum, and cystic formation during disease progression., Conclusion: To our knowledge, this is one of the largest case series of patients with CD which includes a detailed description of the brain MRI findings. The study confirmed many of the previously reported MRI findings but also identified abnormalities that were previously rarely or not described. We speculate that areas of ongoing myelination are particularly vulnerable to changes in CD., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chronic obstructive pulmonary disease (COPD) is strongly linked to cigarette smoke, which contains toxins that induce oxidative stress and airway inflammation, ultimately leading to premature airway epithelial cell senescence and exacerbating COPD progression. Current treatments for COPD are symptomatic and hampered by limited efficacy and severe side effects. This highlights the need to search for an optimal therapeutic candidate to address the root causes of these conditions. This study investigates the possible potential of poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles encapsulating the plant-based bioactive compound 18-β-glycyrrhetinic acid (18βGA) as a strategy to intervene in cigarette smoke extract (CSE)-induced oxidative stress, inflammation, and senescence, in vitro. We prepared 18βGA-PLGA nanoparticles, and assessed their effects on cell viability, reactive oxygen species (ROS) production, anti-senescence properties (expression of senescence-associated β galactosidase and p21 mRNA), and expression of pro-inflammatory genes (CXCL-1, IL-6, TNF-α) and inflammation-related proteins (IL-8, IL-15, RANTES, MIF). The highest non-toxic concentration of 18βGA-PLGA nanoparticles to healthy human broncho epithelial cell line BCiNS1.1 was identified as 5 µM. These nanoparticles effectively mitigated cigarette smoke-induced inflammation, reduced ROS production, protected against cellular aging, and counteracted the effects of CSE on the expression of the inflammation-related genes and proteins. This study underscores the potential of 18βGA encapsulated in PLGA nanoparticles as a promising therapeutic approach to alleviate cigarette smoke-induced oxidative stress, inflammation, and senescence. Further research is needed to explore the translational potential of these findings in clinical and in vivo settings., 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 © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Objective: Intraoperative magnetic resonance imaging (iMRI) use is becoming increasingly widespread in neurosurgical practice, and most of the data reporting its use are in adult populations. There is less evidence on the use of iMRI in pediatric neurosurgery. The aim of this paper was to synthesize the available literature into a systematic review and meta-analysis to evaluate the evidence for iMRI in pediatric neurosurgery, with a particular focus on neuro-oncology and epilepsy surgery., Methods: This review was registered on PROSPERO and conducted according to PRISMA guidelines. A comprehensive search strategy of Medline via Ovid and Embase was conducted with predetermined key terms. Studies in English reporting the outcomes of patients < 21 years of age who underwent neuro-oncological or epilepsy surgery with the use of iMRI were included in the study. The types of studies eligible for inclusion were observational case-control and cohort studies, randomized clinical trials, cross-sectional studies, editorials, case series, and commentaries. Articles were de-duplicated and abstracts independently screened for inclusion by two reviewers. Full texts were screened, and data on demographic characteristics, etiology, outcome (extent of resection for neuro-oncology and Engel class for epilepsy), and technical iMRI data were extracted., Results: Thirty-five articles were included in the review, 25 of which were observational cohort studies. Four articles were suitable for meta-analysis. In total, 1217 patients underwent iMRI-guided neuro-oncology surgery in 26 studies, most commonly for gliomas (n = 443). A total of 148 patients underwent iMRI-guided epilepsy surgery in 9 studies, with focal cortical dysplasia being the most common diagnosis (n = 95). The mean ± SD operating time was 357 ± 94 minutes (12 studies), with a mean of 1.32 scans per patient. There was a mean re-entry rate into the operative field of 42% (across 20 studies). Complications were noted in 21% of epilepsy surgery patients and 11% of neuro-oncology surgery patients. Meta-analysis of 4 eligible studies revealed that iMRI was more likely to lead to better Engel outcomes in terms of seizure freedom (OR 3.84, 95% CI 1.38-10.68, p = 0.69) and complete tumor resection (OR 3.19, 95% CI 0.28-36.92, p = 0.06)., Conclusions: iMRI appears to be a useful adjunct in optimizing resective pediatric epilepsy and neuro-oncology surgery, with a low complication rate.

Synthetic packaging materials are known to cause serious environmental and human health problems. Among the eco-friendly biopolymers from nonfood sources that are suitable for packaging applications, pectin is a promising candidate. However, native pectin films (NPF) exhibit poor mechanical strength, high hydrophilicity, and poor gas diffusion barrier properties. These shortcomings offset the advantages of pectin as a potential packaging material. To address these limitations, in this study, hematite nano ellipsoids (HNEs) were incorporated as fillers to reinforce native pectin films. This reinforcement resulted in substantial improvements in the mechanical properties, hydrophobicity, thermal stability, barrier properties, and optical attributes of pectin films. Compared to NPF, the pectin-hematite composite film exhibited a 35% increase in tensile strength, a 30° increase in contact angle, a 6-fold increase in the oxygen diffusion barrier properties, and a 20% increase in the water vapor barrier properties. This study presents a sustainable, biocompatible, and biodegradable packaging solution by capitalizing on eco-friendly biopolymer and nanoparticle engineering.

During the space travel mission, astronauts' physiological and psychological behavior will alter, and they will start consuming terrestrial drug products. However, factors such as microgravity, radiation exposure, temperature, humidity, strong vibrations, space debris, and other issues encountered, the drug product undergo instability This instability combined with physiological changes will affect the shelf life and diminish the pharmacokinetic and pharmacodynamic profile of the drug product. Consequently, the physicochemical changes will produce a toxic degradation product and a lesser potency dosage form which may result in reduced or no therapeutic action, so the astronaut consumes an additional dose to remain healthy. On long-duration missions like Mars, the drug product cannot be replaced, and the astronaut may relay on the available medications. Sometimes, radiation-induced impurities in the drug product will cause severe problems for the astronaut. So, this review article highlights the current state of various space-related factors affecting the drug product and provides a comprehensive summary of the physiological changes which primarly focus on absorption, distribution, metabolism, and excretion (ADME). Along with that, we insist some of the strategies like novel formulations, space medicine manufacturing from plants, and 3D printed medicine for astronauts in longer-duration missions. Such developments are anticipated to significantly contribute to new developments with applications in both human space exploration and on terrestrial healthcare., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hypothesis: Synthetic micro/nanomotors are gaining extensive attention for various biomedical applications (especially in drug delivery) due to their ability to mimic the motion of biological micro/nanoscale swimmers. The feasibility of these applications relies on tight control of propulsion speed, direction, and type of motion (translation, circular, etc.) along with the exerted self-propulsive force. We propose to exploit the variation of both self-propulsion speed and force of active colloids with different patch coverages (with and without supporting layer) for engineering diffusiophoretic micro/nanomotors., Experiments: The microswimmers were designed at various patch coverages (10°, 30°, and 90°) with (Ti/Pt) and without (Pt) an adhesion layer for the catalytic patch through glancing angle metal deposition (GLAD) technique. Mean-square displacement (MSD) analysis was performed to obtain the self-propulsion parameters like speed and angular speed. Using optical tweezers (OT), the self-propulsive force was measured from the force power spectral density., Findings: The findings of our experiments suggest the non-requirement of any adhesion layer preceding the catalyst deposition since the Pt 10° colloidal batch had the maximal self-propulsion speed (4.61±0.3μm/s) and force (345±57fN) for 5% w/v H 2 O 2 fuel concentration. Moreover, the self-propulsion speed and force decreased with increasing patch size, contrary to theoretical estimates. Also, the self-propulsive force obtained from MSD is 2 to 4 times lower in magnitude than the OT based force values. We believe that the self-propelling motion of the micromotors is possibly hindered due to interactions with the surface of the quartz cuvette during the optical microscopic analysis. Further, the MSD is limited to the self-propulsive motion in two dimensions. On the other hand, OT based force measurement involve trapping the particles in the bulk of the solution entirely avoiding the particle-substrate interactions. Hence, OT based force measurements are better than the propulsion velocity based stokes drag force estimates. We believe that this study can lay the foundation in designing efficient micro/nanomotors for translational biomedical applications., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Swathi Sudhakar reports financial support was provided by India Ministry of Science & Technology Department of Science and Technology. Swathi Sudhakar reports financial support was provided by Ministry of Education. Ethayaraja Mani reports financial support was provided by India Ministry of Science & Technology Department of Science and Technology. If there are other authors, they 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 © 2024 Elsevier Inc. All rights reserved.)

Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem disorders arising from pathogenic variants in glycosylphosphatidylinositol anchor pathway (GPI-AP) genes. Despite associating 24 of at least 31 GPI-AP genes with human neurogenetic disease, prior reports are limited to single genes without consideration of the GPI-AP as a whole and with limited natural history data. In this multinational retrospective observational study, we systematically analyse the molecular spectrum, phenotypic characteristics and natural history of 83 individuals from 75 unique families with IGDs, including 70 newly reported individuals; the largest single cohort to date. Core clinical features were developmental delay or intellectual disability (DD/ID, 90%), seizures (83%), hypotonia (72%) and motor symptoms (64%). Prognostic and biologically significant neuroimaging features included cerebral atrophy (75%), cerebellar atrophy (60%), callosal anomalies (57%) and symmetric restricted diffusion of the central tegmental tracts (60%). Sixty-one individuals had multisystem involvement including gastrointestinal (66%), cardiac (19%) and renal (14%) anomalies. Though dysmorphic features were appreciated in 82%, no single dysmorphic feature had a prevalence >30%, indicating substantial phenotypic heterogeneity. Follow-up data were available for all individuals, 15 of whom were deceased at the time of writing. Median age at seizure onset was 6 months. Individuals with variants in synthesis stage genes of the GPI-AP exhibited a significantly shorter time to seizure onset than individuals with variants in transamidase and remodelling stage genes of the GPI-AP (P = 0.046). Forty individuals had intractable epilepsy. The majority of individuals experienced delayed or absent speech (95%), motor delay with non-ambulance (64%), and severe-to-profound DD/ID (59%). Individuals with a developmental epileptic encephalopathy (51%) were at greater risk of intractable epilepsy (P = 0.003), non-ambulance (P = 0.035), ongoing enteral feeds (P < 0.001) and cortical visual impairment (P = 0.007). Serial neuroimaging showed progressive cerebral volume loss in 87.5% and progressive cerebellar atrophy in 70.8%, indicating a neurodegenerative process. Genetic analyses identified 93 unique variants (106 total), including 22 novel variants. Exploratory analyses of genotype-phenotype correlations using unsupervised hierarchical clustering identified novel genotypic predictors of clinical phenotype and long-term outcome with meaningful implications for management. In summary, we expand both the mild and severe phenotypic extremities of the IGDs, provide insights into their neurological basis, and vitally, enable meaningful genetic counselling for affected individuals and their families., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background and Purpose: Neuronal ceroid lipofuscinoses (NCL) are a group of neurodegenerative disorders. Recently, enzyme replacement therapy (ERT) was approved for CLN2, a subtype of NCL. The aim of this study was to quantify brain volume loss in CLN2 disease of patients on ERT in comparison to a natural history cohort using magnetic resonance imaging (MRI)., Materials and Methods: Nineteen (13 female, 6 male) patients with CLN2 disease at one UK center were studied using serial 3D T1-weighted MRI (follow-up time, 1 to 9 years). Brain segmentation was done using FreeSurfer. Volume measurements for supratentorial grey and white matter, deep grey matter (basal ganglia/thalami), lateral ventricles, and cerebellar grey and white matter were recorded. The volume change over time was analyzed using a linear mixed-effects model excluding scans before treatment start. Comparison was made to a published natural history cohort of 12 patients (8 female, 4 male) which was reanalyzed using the same method., Results: Brain volume loss of all segmented brain regions was much slower in treated patients compared to the natural history cohort. For example, supratentorial grey matter volume in treated patients decreased by 3±0.74% (p<0.001) annually compared to an annual volume loss of 16.8±1.5% (p<0.001) in the natural history cohort., Conclusions: Our treatment cohort showed a significantly slower rate of brain parenchymal volume loss compared to a natural history cohort in several anatomical regions. Our results complement prior clinical data which found a positive response to ERT. We demonstrate that automated MRI volumetry is a sensitive tool to monitor treatment response in children with CLN2 disease., Abbreviations: NCL = Neuronal Ceroid Lipofuscinosis, CLN2 = Neuronal Ceroid Lipofuscinosis type 2, TPP1 = tripeptidyl peptidase 1, ERT = enzyme replacement therapy, EMA = European Medicines Agency, ICV = intra-cerebro-ventricular reservoir., Competing Interests: Angela Schulz and Paul Gissen have been the recipients of research funding from Biomarin. This work was supported by funding from the United Kingdom Medical Research Council grants MR/N019075/1 and MR/R026084/1 to Paul Gissen. All other authors declare no conflicts of interest related to the content of this article., (© 2024 by American Journal of Neuroradiology.)

Flash nanoprecipitation is a simple and scalable method to produce nanoparticles by rapid mixing of a polymer solution with an antisolvent. High-speed mixing devices for the continuous synthesis of polymeric nanoparticles and drug-encapsulated nanoparticles have been designed. In this work, we demonstrate a different approach to induce flash nanoprecipitation using the differential evaporation of solvents in a sessile drop. To show proof of concept, we use polymethyl-methacrylate (PMMA) dissolved in a tetrahydrofuran (THF)-water mixture as a model system. A sessile drop of the polymer solution is allowed to dry under controlled conditions. The sessile drops of the PMMA-THF-water ternary mixture are observed to dry in the constant radius mode. As THF in the drop evaporates faster than water, PMMA supersaturates and precipitates as nanoparticles. Although coffee-ring formation is well-studied in the drying of colloidal suspensions, this work demonstrates the formation of nanoparticles in situ due to a change of solvent quality and subsequent deposition of particles at the pinned contact line. Using the theory of drying of binary solutions, we calculate the temporal variation of composition. The drying paths passing through the low-concentration branch of the binodal give rise to nanoparticles, whereas those passing through the high-concentration branch yield porous films. Spherical polymeric nanoparticles in the size range of 250-700 nm were synthesized using this technique starting from drops with different initial polymer concentration. The method is a cost-effective (no high-speed mixing is required) and scalable alternative to conventional flash nanoprecipitation for synthesizing polymeric nanoparticles for potential applications in drug delivery, diagnostics, and polymer recycling.

We aimed to investigate the potential added value of postmortem MRI (PMMRI) in sudden unexpected infant death (SUID) cases referred to our center between September 2020 and June 2023. Ultimately, 19 SUID cases underwent PMMRI alongside standard autopsy procedures, which included technical examinations such as postmortem CT (PMCT). Four radiologists, two with prior PMMRI experience, provided structured reports following consensus. For each case, the responsible forensic medicine specialist documented the cause of death before and after reviewing the PMMRI report. Additionally, they assessed the overall impact of the PMMRI report and had the opportunity to provide written comments. The results of our study indicate that none of the PMMRI reports altered the prior determined cause of death, which included cases of infection, asphyxia, and sudden infant death syndrome (SIDS). However, we observed a moderate impact in one case and a low impact in 10 cases. The moderate impact arose from the PMMRI report identifying hypoxic-ischemic changes, where histologic examination of the brain was perceived as normal. Conversely, in the 10 cases with a low impact, the PMMRI reports supported the autopsy findings, specifically indicating brain injury and intra-alveolar cellular infiltrates. In conclusion, our study suggests that while PMMRI may not be pivotal in determining the cause of death in SUID cases, it could aid in detecting hypoxic-ischemic changes and reinforcing brain and lung observations. However, distinguishing genuine lung pathology from postmortem changes using PMMRI remains challenging. Further research is warranted to clarify the role of PMMRI in forensic SUID investigations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cytoplasmic and nuclear iron-sulfur (Fe-S) enzymes that are essential for genome maintenance and replication depend on the cytoplasmic Fe-S assembly (CIA) machinery for cluster acquisition. The core of the CIA machinery consists of a complex of CIAO1, MMS19 and FAM96B. The physiological consequences of loss of function in the components of the CIA pathway have thus far remained uncharacterized. Our study revealed that patients with biallelic loss of function in CIAO1 developed proximal and axial muscle weakness, fluctuating creatine kinase elevation, and respiratory insufficiency. In addition, they presented with CNS symptoms including learning difficulties and neurobehavioral comorbidities, along with iron deposition in deep brain nuclei, mild normocytic to macrocytic anemia, and gastrointestinal symptoms. Mutational analysis revealed reduced stability of the variants compared with WT CIAO1. Functional assays demonstrated failure of the variants identified in patients to recruit Fe-S recipient proteins, resulting in compromised activities of DNA helicases, polymerases, and repair enzymes that rely on the CIA complex to acquire their Fe-S cofactors. Lentivirus-mediated restoration of CIAO1 expression reversed all patient-derived cellular abnormalities. Our study identifies CIAO1 as a human disease gene and provides insights into the broader implications of the cytosolic Fe-S assembly pathway in human health and disease.

Safrole is a natural product present in many plants and plant products, including spices and essential oils. During cellular metabolism, it converts to a highly reactive trans-isosafrole (SF) intermediate that reacts with genomic DNA and forms N 2 -SF-dG and N 6 -SF-dA DNA adducts, which are detected in the oral tissue of cancer patients with betel quid chewing history. To study the SF-induced carcinogenesis and to probe the role of low fidelity translesion synthesis (TLS) polymerases in bypassing SF adducts, herein, we report the synthesis of N 2 -SF-dG modified DNAs using phosphoramidite chemistry. The N 2 -SF-dG modification in the duplex DNA does not affect the thermal stability and retains the B-form of helical conformation, indicating that this adduct may escape the radar of common DNA repair mechanisms. Primer extension studies showed that the N 2 -SF-dG adduct is bypassed by human TLS polymerases hpolκ and hpolη, which perform error-free replication across this adduct. Furthermore, molecular modeling and dynamics studies revealed that the adduct reorients to pair with the incoming nucleotide, thus allowing the effective bypass. Overall, the results indicate that hpolκ and hpolη do not distinguish the N 2 -SF-dG adduct, suggesting that they may not be involved in the safrole-induced carcinogenicity.

Background Lateral epicondylitis is a common condition involving the arm. It is caused by degenerative changes or overuse of the tendon connecting the elbow joint to the forearm muscle. Plyometric and TheraBand FlexBar (Theraband, Akron, OH, USA) exercises can relieve elbow discomfort, soreness, and weakness. This study examines the effects of plyometric and TheraBand FlexBar exercises with ultrasound on tennis elbow patients. Methodology It is an experimental study comprising a total of 30 participants, including individuals of both genders with age groups of 20-40 years were selected by specific criteria for inclusion and exclusion. The participants were randomly assigned into two groups. Group A received plyometric exercises with ultrasound, whereas Group B received TheraBand FlexBar exercises with ultrasound. The outcome measures utilized in this study include patient-rated tennis elbow evaluation (PRTEE) and visual analog scale (VAS) for evaluating the functional disability of the hand, arm, and shoulder. Results The results showed a substantial reduction in mean values in Group A compared to Group B, with a p-value of less than 0.001, indicating that plyometric exercises with ultrasound were more effective than TheraBand FlexBar exercises. Conclusion Plyometric exercises combined with ultrasound therapy demonstrated significant reductions in discomfort and improvements in function, with plyometric exercises showing superior efficacy compared to TheraBand FlexBar exercises., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee, Faculty of Physiotherapy, Dr. M.G.R. Educational & Research Institute, Chennai issued approval E-29/PHYSIO/IRB/2023-2024. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, G et al.)

Rheumatoid Arthritis (RA) is a progressive autoimmune condition inflicting serious threats to people's life and health by causing severe pain and joint destruction. It affects not only bones and joints but also causes comorbid conditions and shortens the lifetime. The interactions and synergistic effects of comorbid disease with RA are not yet well studied. Hence, understanding how these conditions will collectively affect the progression and outcome of RA is the current area of research. Identification of RA and comorbidities associated with target genes may uncover diagnosis and treatment methodologies. This review is to provide an overview of the interlinking approach of Rheumatoid Arthritis with its comorbid conditions and its systemic complications using bioinformatic techniques which would be useful to identify the genes and pathways that are in common for both RA and comorbid diseases. It would also emphasize the significance of bioinformatics in comparing the pathological features of RA and comorbid diseases. With the help of bioinformatics, valuable insights into the mechanism underlying Rheumatoid arthritis and comorbid diseases would be better understood., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

As human progenitor cells differentiate into neurons, the activities of many genes change; these changes are maintained within a narrow range, referred to as genome homeostasis. This process, which alters the synchronization of the entire expressed genome, is distorted in neurodevelopmental diseases such as schizophrenia. The coordinated gene activity networks formed by altering sets of genes comprise recurring coordination modules, governed by the entropy-controlling action of nuclear FGFR1, known to be associated with DNA topology. These modules can be modeled as energy-transferring circuits, revealing that genome homeostasis is maintained by reducing oscillations (noise) in gene activity while allowing gene activity changes to be transmitted across networks; this occurs more readily in neuronal committed cells than in neural progenitors. These findings advance a model of an "entangled" global genome acting as a flexible, coordinated homeostatic system that responds to developmental signals, is governed by nuclear FGFR1, and is reprogrammed in disease.

Metallic nanomaterials have gained significant attention in cancer therapy as potential nanocarriers due to their unique properties at the nanoscale. However, nanomaterials face several drawbacks, including biocompatibility, stability, and cellular uptake. Hematite (α-Fe 2 O 3 ) nanoparticles are emerging as promising nano-carriers to reduce adverse outcomes of conventional chemotherapeutics. However, the shape-mediated drug carrier mechanics of hematite nanomaterials are not raveled. In this study, we tailored hematite nanoparticles in ellipsoidal (EHNP) and spherical (SHNP) shapes with excellent biocompatibility and efficient drug encapsulation and release. We elucidate that EHNP exhibits higher cellular uptake than SHNP. With effective cellular internalization, the cisplatin-loaded EHNP showed excellent cytotoxicity with an IC 50 value of 200 nM compared to the cisplatin-loaded SHNP. The flow cytometry cell sorting (FACS) analysis showed a four-fold increase in cell death by arresting the cells at the G0/G1 and G1 phases for cis -EHNP compared to cis -SHNP. The results show that ellipsoidal-shaped hematite nanoparticles can act as attractive nanocarriers with improved therapeutic efficacy in cancer therapy.

Tobacco smoking is a leading cause of preventable mortality, and it is the major contributor to diseases such as COPD and lung cancer. Cigarette smoke compromises the pulmonary antiviral immune response, increasing susceptibility to viral infections. There is currently no therapy that specifically addresses the problem of impaired antiviral response in cigarette smokers and COPD patients, highlighting the necessity to develop novel treatment strategies. 18-β-glycyrrhetinic acid (18-β-gly) is a phytoceutical derived from licorice with promising anti-inflammatory, antioxidant, and antiviral activities whose clinical application is hampered by poor solubility. This study explores the therapeutic potential of an advanced drug delivery system encapsulating 18-β-gly in poly lactic-co-glycolic acid (PLGA) nanoparticles in addressing the impaired antiviral immunity observed in smokers and COPD patients. Exposure of BCi-NS1.1 human bronchial epithelial cells to cigarette smoke extract (CSE) resulted in reduced expression of critical antiviral chemokines (IP-10, I-TAC, MIP-1α/1β), mimicking what happens in smokers and COPD patients. Treatment with 18-β-gly-PLGA nanoparticles partially restored the expression of these chemokines, demonstrating promising therapeutic impact. The nanoparticles increased IP-10, I-TAC, and MIP-1α/1β levels, exhibiting potential in attenuating the negative effects of cigarette smoke on the antiviral response. This study provides a novel approach to address the impaired antiviral immune response in vulnerable populations, offering a foundation for further investigations and potential therapeutic interventions. Further studies, including a comprehensive in vitro characterization and in vivo testing, are warranted to validate the therapeutic efficacy of 18-β-gly-PLGA nanoparticles in respiratory disorders associated with compromised antiviral immunity., Competing Interests: Declaration of Competing Interest The authors of the manuscript “18-β-glycyrrhetinic acid-loaded polymeric nanoparticles attenuate cigarette smoke-induced markers of impaired antiviral response in vitro”, submitted to the journal “Pathology - Research and Practice”, have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Primary dysmenorrhea, commonly known as menstrual cramps, is a prevalent gynecological issue that impacts many women in their childbearing age. It manifests as reoccurring, cramp-like lower abdominal pain, usually commencing right prior to or during the menstrual period. These painful sensations can be severe, extending to the lower back and upper thighs can greatly disrupt a woman's daily life and overall well-being. The optimal exercise approach is needed for individuals seeking relief from primary dysmenorrhea, allowing healthcare providers and women themselves to make informed decisions regarding their treatment options. Though many forms of exercise interventions exist in the treatment of primary dysmenorrhea, this study aims to compare two forms of intervention namely pilates and gym ball exercises on pain and menstrual distress among women with Primary Dysmenorrhea., Methods: This experimental comparative study was carried out with 30 young female participants over a 12-week period. Participant recruitment was done through a simple random sampling method. The criteria of inclusion encompassed young females aged 17-25 years, those in good health, and those experiencing primary dysmenorrhea. Exclusion criteria included secondary dysmenorrhea, medication use, polycystic ovarian syndrome, bleeding disorders, positive pregnancy tests, breastfeeding, and other medical conditions. Group A received Pilates exercises, while Group B underwent Gym ball exercises. The assessment of both groups' menstrual distress levels was conducted using the Moos Menstrual Distress Questionnaire (MDQ) and pain scores using the Visual Analog Scale (VAS)., Result: In the statistical analysis, Group A (Pilates Exercises) showed a significantly lower mean value (2.60) on the VAS compared to Group B (Swiss Ball Exercises) (5.46), with both groups experiencing a notable reduction in post-test scores (p ≤ 0.001). Additionally, on the MOOS MDQ score, Group A (Pilates Exercises) achieved a lower mean value (79.33) compared to Group B (Swiss Ball Exercises) (103.26), with both groups demonstrating a significant decrease in post-test scores (p ≤ 0.001)., Conclusion: In conclusion, this study underscores the significance of exercise therapy, particularly Pilates exercises, as a holistic approach to addressing primary dysmenorrhea, improving physical well-being, and enhancing the overall quality of life., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kirthika S et al.)

Understanding the structure and recognition of highly conserved regulatory segments of the integrated viral DNA genome that forms unique topologies can greatly aid in devising novel therapeutic strategies to counter chronic infections. In this study, we configured a probe system using highly environment-sensitive nucleoside analogs, 5-fluoro-2'-deoxyuridine (FdU) and 5-fluorobenzofuran-2'-deoxyuridine (FBFdU), to investigate the structural polymorphism of HIV-1 long terminal repeat (LTR) G-quadruplexes (GQs) by fluorescence and 19 F NMR. FdU and FBFdU, serving as hairpin and GQ sensors, produced distinct spectral signatures for different GQ topologies adopted by LTR G-rich oligonucleotides. Importantly, systematic 19 F NMR analysis in Xenopus laevis oocytes gave unprecedented information on the structure adopted by the LTR G-rich region in the cellular environment. The results indicate that it forms a unique GQ-hairpin hybrid architecture, a potent hotspot for selective targeting. Furthermore, structural models generated using MD simulations provided insights on how the probe system senses different GQs. Using the responsiveness of the probes and Taq DNA polymerase stop assay, we monitored GQ- and hairpin-specific ligand interactions and their synergistic inhibitory effect on the replication process. Our findings suggest that targeting GQ and hairpin motifs simultaneously using bimodal ligands could be a new strategy to selectively block the viral replication., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Tembotrione is a triketone herbicide widely used for broad-spectrum weed control in corn but not registered for use in wheat. A wide collection of spring, winter, and EMS-derived mutant lines of wheat was evaluated for their response to tembotrione treatment. Two winter wheat (WW) genotypes (WW-1 and WW-2) were found to be least sensitive to this herbicide, surviving >6 times the field recommended dose (92 g ai ha -1 ) compared to the most sensitive genotype (WW-24). Further, HPLC analysis using [ 14 C] tembotrione suggested that both WW-1 and WW-2 metabolized tembotrione rapidly to nontoxic metabolites. Pretreatment with a P450 inhibitor (malathion) followed by tembotrione application increased the sensitivity of WW-1 and WW-2 genotypes to this herbicide, suggesting likely involvement of P450 enzymes in metabolizing tembotrione similar to corn. Overall, our results suggest that the genotypes WW-1 and WW-2 can potentially be used to develop tembotrione-resistant wheat varieties.

Dysraphic malformations of the spine and spinal cord (DMSSC) represent a spectrum of common congenital anomalies typically (though not exclusively) affecting the lower spinal segments. These may be responsible for varying degrees of neurologic, orthopedic, and urologic morbidity. With advances in neuroimaging, it is now possible to better diagnose and evaluate these disorders both prenatally and postnatally. Neuroimaging, performed at the right time and with technique optimization, is integral in guiding clinical management. However, the terminology used to describe these lesions has become increasingly confusing, and there is a lack of consensus regarding the essential radiologic features and their clinical weighting. This variability in radiologic practice risks unstructured decision making and increases the likelihood of suboptimal, less informed clinical management. In this manuscript, the first of a series of consensus statements, we outline a standardized international consensus statement for the radiologic evaluation of children with suspected DMSSC derived from a critical review of the literature, and the collective clinical experience of a multinational group of experts. We provide recommendations for plain radiography, sonography, CT, and MR imaging in the evaluation of DMSSC with an emphasis on technique of imaging and imaging protocols., (© 2024 by American Journal of Neuroradiology.)

This study delves into the potential of chito-oligosaccharides (COS) to promote osteoblast differentiation and prevent osteoporosis, utilizing experiments with mouse MSCs and the zebrafish model. The preliminary biocompatibility study affirms the non-toxic nature of COS across various concentrations. In the osteoblast differentiation study, COS enhances ALP activity and calcium deposition at the cellular level. Moreover, COS induces the upregulation of molecular markers, including Runx2, Type I collagen, ALP, osteocalcin, and osteonectin in mouse MSCs. Zebrafish studies further demonstrate COS's anti-osteoporotic effects, showcasing its ability to expedite fin fracture repair, vertebral mineralization, and bone mineralization in dexamethasone-induced osteoporosis models. The scale regenerative study reveals that COS mitigates the detrimental effects of dexamethasone induced osteoclastic activity, reducing TRAP and hydroxyproline levels while elevating the expression of Runx2a MASNA isoform, collagen2α, OC, and ON mRNAs. Additionally, COS enhances calcium and phosphorus levels in regenerated scales, impacting the bone-healthy calcium-to‑phosphorus ratio. The study also suggests that COS modulates the MMP3-Osteopontin-MAPK signaling pathway. Overall, this comprehensive investigation underscores the potential of COS to prevent and treat osteoporosis. Its multifaceted cellular and molecular effects, combined with in vivo bone regeneration and repair, propose that COS may be effective in addressing osteoporosis and related bone disorders. Nonetheless, further research is imperative to unravel underlying mechanisms and optimize clinical applications., 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 © 2024 Elsevier B.V. All rights reserved.)

G-rich sequences are present across the genome and can fold to form dynamic secondary structures, namely, G-quadruplexes (G4). These structures play a pivotal role in regulating numerous biological processes including replication, transcription, and translation. Therefore, targeting these structures using molecular scaffolds is an attractive approach to modulating their functions. Herein, we report the synthesis of three estrone-based derivatives ( Est-1 , Est-2 , and Est-3 ) with a nonplanar core and a cationic alkyl side chain as G4 stabilizers. CD melting and polymerase stop assay results indicate that these ligands preferentially stabilize parallel c-MYC and c-KIT1 G4s over the other G4s and duplex DNAs. The ligand Est-3 shows cytotoxicity against cancer cell lines and effectively downregulates the c-KIT gene in HepG2 cell lines. Molecular modeling and dynamics studies showed that the ligand prefers stacking over the 5'-quartet of c-MYC G4 using the aromatic ring of the ligand. Overall, the findings of this study demonstrate that even G4 ligands can accommodate nonplanar scaffolds, which opens up new avenues for ligand design., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Breast cancer has a poor prognosis due to the toxic side effects associated with high doses of chemotherapy. Liposomal drug encapsulation has resulted in clinical success in enhancing chemotherapy tolerability. However, the formulation faces severe limitations with a lack of colloidal stability, reduced drug efficiency, and difficulties in storage conditions. Nanoarchaeosomes (NA) are a new generation of highly stable nanovesicles composed of the natural ether lipids extracted from archaea. In our study, we synthesized and characterized the NA, evaluated their colloidal stability, drug release potential, and anticancer efficacy. Transmission electron microscopy images have shown that the NA prepared from the hyperthermophilic archaeon Aeropyrum pernix K1 was in the size range of 61 ± 3 nm. The dynamic light scattering result has confirmed that the NA were stable at acidic pH (pH 4) and high temperature (70 °C). The NA exhibited excellent colloidal stability for 50 days with storage conditions at room temperature. The cell viability results have shown that the pure NA did not induce cytotoxicity in NIH 3T3 fibroblast cells and are biocompatible. Then NA were loaded with doxorubicin (NAD), and FTIR and UV-vis spectroscopy results have confirmed high drug loading efficiency of 97 ± 1% with sustained drug release for 48 h. The in vitro cytotoxicity studies in MCF-7 breast cancer cell lines showed that NAD induced cytotoxicity at less than 10 nM concentration. Fluorescence-activated cell sorting (FACS) results confirmed that NAD induced late apoptosis in nearly 92% of MCF-7 cells and necrosis in the remaining cells with cell cycle arrest at the G0/G1 phase. Our results confirmed that the NA could be a potential next-generation carrier with excellent stability, high drug loading efficiency, sustained drug release ability, and increased therapeutic efficacy, thus reducing the side effects of conventional drugs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Tissue engineering is an emerging technological field that aims to restore and replace human tissues. A significant number of individuals require bone replacement annually as a result of skeletal abnormalities or accidents. In recent decades, notable progress has been made in the field of biomedical research, specifically in the realm of sophisticated and biocompatible materials. The purpose of these biomaterials is to facilitate bone tissue regeneration. Carbon nanomaterial-based scaffolds are particularly notable due to their accessibility, mechanical durability, and biofunctionality. The scaffolds exhibit the capacity to enhance cellular proliferation, mitigate cell damage, induce bone tissue growth, and maintain biological compatibility. Therefore, they play a crucial role in the development of the bone matrix and the necessary cellular interactions required for bone tissue restoration. The attachment, growth, and specialization of osteogenic stem cells on biomaterial scaffolds play critical roles in bone tissue engineering. The optimal biomaterial should facilitate the development of bone tissue in a manner that closely resembles that of human bone. This comprehensive review encompasses the examination of graphene oxide (GO), carbon nanotubes (CNTs), fullerenes, carbon dots (CDs), nanodiamonds, and their respective derivatives. The biomaterial frameworks possess the ability to replicate the intricate characteristics of the bone microenvironment, thereby rendering them suitable for utilization in tissue engineering endeavors., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Introduction: Chemotherapy is an integral part of cancer management which is associated with phlebitis in around 70% of patients receiving intravenous chemotherapy infusion. Thus, we aimed to estimate the incidence, severity, and management of phlebitis associated with chemotherapy infusion among cancer patients., Methods: A prospective study was conducted among 145 patients receiving intravenous chemotherapy for the duration of six months in the oncology department. The relevant data for phlebitis was obtained and assessed using Phlebitis Grading Scale and Visual Analogue Scale for the assessment of severity and pain due to phlebitis, respectively., Results: Out of 145 patients, female (56.6%) patients predominated over male patients (43.5%) with a mean age of 53.5 ± 11.82 years. Phlebitis was encountered in 30.34% of patients among whom 22.8% (33) were females followed by 7.6% were males and the majority of patients (13.1%) were from the 46 to 60 years age group. Phlebitis was observed frequently among stage 2 (11%) and satge 4 (11%) patients. The highest incidence of phlebitis was seen among hypertensive (34.09%) and diabetic patients (27.27%) followed by those receiving chemotherapy through the 20-gauge intravenous cannula (22.8%) and 22-gauge (6.9%). Platinum compounds (56.8%) were commonly associated with phlebitis, followed by cyclophosphamide (20.5%). Heparin and benzyl nicotinate topical gel were used to treat phlebitis., Conclusion: Platinum and cyclophosphamide are commonly associated with phlebitis which can be managed by topical heparin plus benzyl nicotinate. Phlebitis shouldn't be ignored as it has a high incidence, affects the quality of life, and increases the treatment burden., Competing Interests: Author contributionsUVM and VS designed the study; SS, AJ, NNH collected the data; RKC performed analysis and interpreted the results; UVM drafted the manuscript. All authors reviewed and approved the final version of the manuscript. Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction Asthma is a chronic respiratory condition characterized by inflammation of the airway leading to breathlessness. Exercise training has been recognized as a valuable component in the management of asthma, enhancing lung function and overall well-being. Bicycle ergometer training and Nordic walking are two distinct forms of exercise that have been shown to improve cardiovascular fitness and respiratory function. Despite the potential benefits of these exercises, limited research directly compares their efficacy in improving functional capacity specifically in asthma patients. The study thus aims to address this gap by providing personalized, tailored exercise programs for asthma patients. Methods A single-blinded experimental study using a simple random sampling method was conducted. A sample of 40 subjects was recruited for the study based on inclusion and exclusion criteria and were assigned into two groups. Group A subjects were trained with a bicycle ergometer and Group B subjects were trained with Nordic walking. The intervention was given to both groups for 12 weeks. The outcome measures used were the six-minute walk test, Modified Borg Scale, and Mini Asthma Quality of Life Questionnaire. Results A baseline analysis of outcome measures was done, which was followed up by a post-test analysis after 12 weeks. Pre-test and post-test data were compared using a paired t-test. Intergroup analysis was done by an independent t-test. Both groups showed significant improvement in post-test results. On comparing the two groups, Group A showed significant improvement as compared to Group B. Conclusion The study concludes that bicycle ergometer training is effective in improving functional capacity and enhancing the quality of life in asthma patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Sivagnanam et al.)

Background: Cannabis use has been linked to psychotic disorders but this association has been primarily observed in the Global North. This study investigates patterns of cannabis use and associations with psychoses in three Global South (regions within Latin America, Asia, Africa and Oceania) settings., Methods: Case-control study within the International Programme of Research on Psychotic Disorders (INTREPID) II conducted between May 2018 and September 2020. In each setting, we recruited over 200 individuals with an untreated psychosis and individually-matched controls (Kancheepuram India; Ibadan, Nigeria; northern Trinidad). Controls, with no past or current psychotic disorder, were individually-matched to cases by 5-year age group, sex and neighbourhood. Presence of psychotic disorder assessed using the Schedules for Clinical Assessment in Neuropsychiatry and cannabis exposure measured by the World Health Organisation Alcohol, Smoking and Substance Involvement Screening Test (ASSIST)., Results: Cases reported higher lifetime and frequent cannabis use than controls in each setting. In Trinidad, cannabis use was associated with increased odds of psychotic disorder: lifetime cannabis use (adj. OR 1.58, 95% CI 0.99-2.53); frequent cannabis use (adj. OR 1.99, 95% CI 1.10-3.60); cannabis dependency (as measured by high ASSIST score) (adj. OR 4.70, 95% CI 1.77-12.47), early age of first use (adj. OR 1.83, 95% CI 1.03-3.27). Cannabis use in the other two settings was too rare to examine associations., Conclusions: In line with previous studies, we found associations between cannabis use and the occurrence and age of onset of psychoses in Trinidad. These findings have implications for strategies for prevention of psychosis.

Amyloid-β [Aβ(1-40)] aggregation into a fibrillar network is one of the major hallmarks of Alzheimer's disease (AD). Recently, a few studies reported that polyphosphate (polyP), an anionic biopolymer that participates in various cellular physiological processes in humans, induces fibrilization in many amyloidogenic proteins [ 2020 Alzheimer's Disease Facts and Figures ; John Wiley and Sons Inc., 2020; Tanzi, R. E.; Bertram, L. Cell 2005, 120, 545-555; Selkoe, D. J. Proc. Natl. Acad. Sci. U.S.A. 1995, 275, 630-631; and Rambaran, R. N.; Serpell, L. C. Prion 2008, 2, 112-117]. However, the role of polyP in Aβ(1-40) fibrilization and the underlying mechanism are unclear. In this study, we report experimental investigations on the role of polyP in the fibrilization kinetics of Aβ(1-40). It is found that polyP exhibits a dual effect depending upon the pH value. At pH = 7 (neutral), polyP inhibits amyloid fibrilization in a dose-dependent manner similar to negatively charged nanoparticles. On the contrary, at pH = 3 (acidic), polyP accelerates amyloid fibrilization kinetics via liquid-liquid phase separation (LLPS), wherein the protein-rich droplets contain mature fibrils. In the parameter space spanned by concentrations of Aβ(1-40) and polyP, a phase diagram is constructed to demark the domain where LLPS is observed at pH = 3. Characterization of the protein aggregates, secondary structure content in the aggregates, and cell viability studies in the presence of aggregates are discussed at both pH values. This study reveals that anionic biopolymers can modulate amyloid fibrilization kinetics, linked to neurodegenerative diseases, depending upon their local concentrations and pH.

Background and Purpose: Although cardinal imaging features for the diagnostic criteria of the Dandy-Walker phenotype have been recently defined, there is a large range of unreported malformations among these patients. The brainstem, in particular, deserves careful attention because malformations in this region have potentially important implications for clinical outcomes. In this article, we offer detailed information on the association of brainstem dysgenesis in a large, multicentric cohort of patients with the Dandy-Walker phenotype, defining different subtypes of involvement and their potential clinical impact., Materials and Methods: In this established multicenter cohort of 329 patients with the Dandy-Walker phenotype, we include and retrospectively review the MR imaging studies and clinical records of 73 subjects with additional brainstem malformations. Detailed evaluation of the different patterns of brainstem involvement and their potential clinical implications, along with comparisons between posterior fossa measurements for the diagnosis of the Dandy-Walker phenotype, was performed among the different subgroups of patients with brainstem involvement., Results: There were 2 major forms of brainstem involvement in patients with Dandy-Walker phenotype including the following: 1) the mild form with anteroposterior disproportions of the brainstem structures "only" (57/73; 78%), most frequently with pontine hypoplasia (44/57; 77%), and 2) the severe form with patients with tegmental dysplasia with folding, bumps, and/or clefts (16/73; 22%). Patients with severe forms of brainstem malformation had significantly increased rates of massive ventriculomegaly, additional malformations involving the corpus callosum and gray matter, and interhemispheric cysts. Clinically, patients with the severe form had significantly increased rates of bulbar dysfunction, seizures, and mortality., Conclusions: Additional brainstem malformations in patients with the Dandy-Walker phenotype can be divided into 2 major subgroups: mild and severe. The severe form, though less prevalent, has characteristic imaging features, including tegmental folding, bumps, and clefts, and is directly associated with a more severe clinical presentation and increased mortality., (© 2023 by American Journal of Neuroradiology.)

Background Delayed-onset muscle soreness (DOMS) is a common condition in athletes characterized by muscle pain and stiffness after intense or unfamiliar exercise. It significantly impairs an athlete's performance by reducing muscle strength, flexibility, and overall physical capacity, often leading to suboptimal training or competition outcomes. Managing and mitigating DOMS is crucial for athletes to maintain peak performance and prevent potential injuries. The evaluation of effective treatment techniques is essential for expediting DOMS recovery by identifying biomarkers of skeletal muscle damage. This approach not only aids in optimizing recovery strategies but also contributes to the rehabilitation process, enabling athletes to return to peak performance quickly and safely. This study aims to evaluate the effects of shock wave therapy and diclofenac phonophoresis on serum creatine kinase levels in novice athletes suffering from DOMS in comparison to a control group. This research aims to assess the potential benefits of these therapeutic interventions in reducing skeletal muscle damage and enhancing recovery for individuals new to athletic training. Methodology A total of 48 novice athletes were recruited using simple random sampling and the block randomization approach to participate in this single-blind, multi-group, repeated-measures design. Male novice athletes in the age group of 18-25 years were included, and athletes with elevated serum creatine kinase variables at baseline measurements were excluded from the study. Before obtaining a written informed consent form, athletes were made aware of the procedure and associated risks. Group A received focused shock wave therapy, Group B received diclofenac phonophoresis, while Group C received no treatment. The Epley formula was used to compute the one-repetition maximum for each subject. Blood samples were taken at the baseline, 24, 48, 72, and 96 hours. Blood samples were taken before initiation of the study, as well as 24 hours, 48 hours, 72 hours, and 96 hours after DOMS was induced. Creatine kinase skeletal muscle biomarker was used as a dependent variable. Results In the evaluation of serum creatine kinase levels using analysis of variance (ANOVA), no statistically significant differences were observed between the three groups at baseline and 24-hour measurements (p > 0.05). However, statistically significant differences were found between the three groups at 48 hours, 72 hours, and 96 hours (p < 0.05). The repeated-measures ANOVA revealed significant overall changes in creatine kinase levels within the three groups, indicating time-dependent effects (p < 0.05). Specifically, during the 48 to 96-hour interval, the shock wave therapy group showed a lower mean value compared to the diclofenac phonophoresis group, followed by the control group. Conclusions The study demonstrates that a single administration of focused shock wave therapy effectively mitigated the elevation of creatine kinase levels in novice athletes with DOMS, surpassing the outcomes of diclofenac phonophoresis and the control group. These findings suggest the potential benefits of shock wave therapy in accelerating recovery from DOMS in the athletic population., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Sudhakar et al.)

The secondary metabolites of polypropanoids, methyleugenol (MEG), and estragole (EG), found in many herbs and spices, are commonly used as food flavoring agents and as ingredients in cosmetics. MEG and EG have been reported to cause hepatocarcinogenicity in rodents, human livers, and lung cells. The formation of N 2 -dG and N 6 -dA DNA adducts is primarily attributed to the carcinogenicity of these compounds. Therefore, these compounds have been classified as "possible human carcinogens" by the International Agency for Research on Cancer and "reasonably anticipated to be a human carcinogen" by the National Toxicology Program. Herein, we report the synthesis of the N 2 -MEG-dG and N 2 -EG-dG modified oligonucleotides to study the mutagenicity of these DNA adducts. Our studies show that N 2 -MEG-dG and N 2 -EG-dG could be bypassed by human translesion synthesis (TLS) polymerases hpolκ and hpolη in an error-free manner. The steady-state kinetics of dCTP incorporation by hpolκ across N 2 -MEG-dG and N 2 -EG-dG adducts show that the catalytic efficiencies ( k cat / K m ) were ∼2.5- and ∼4.4-fold higher, respectively, compared to the unmodified dG template. A full-length primer extension assay demonstrates that hpolκ exhibits better catalytic efficiency than hpolη. Molecular modeling and dynamics studies capturing pre-insertion, insertion, and post-insertion steps reveal the structural features associated with the efficient bypass of the N 2 -MEG-dG adduct by hpolκ and indicate the reorientation of the adduct in the active site allowing the successful insertion of the incoming nucleotide. Together, these results suggest that though hpolκ and hpolη perform error-free TLS across MEG and EG during DNA replication, the observed carcinogenicity of these adducts could be attributed to the involvement of other low fidelity polymerases.

Background: MAPK-activated protein kinase 5 (MAPKAPK5) is an essential enzyme for diverse cellular processes. Dysregulation of the pathways regulated by MAPKAPK enzymes can lead to the development of variable diseases. Recently, homozygous loss-of-function variants in MAPKAPK5 were reported in four patients from three families presenting with a recognisable neurodevelopmental disorder, so-called 'neurocardiofaciodigital' syndrome., Objective and Methods: In order to improve characterisation of the clinical features associated with biallelic MAPKAPK5 variants, we employed a genotype-first approach combined with reverse deep-phenotyping of three affected individuals., Results: In the present study, we identified biallelic loss-of-function and missense MAPKAPK5 variants in three unrelated individuals from consanguineous families. All affected individuals exhibited a syndromic neurodevelopmental disorder characterised by severe global developmental delay, intellectual disability, characteristic facial morphology, brachycephaly, digital anomalies, hair and nail defects and neuroradiological findings, including cerebellar hypoplasia and hypomyelination, as well as variable vision and hearing impairment. Additional features include failure to thrive, hypotonia, microcephaly and genitourinary anomalies without any reported congenital heart disease., Conclusion: In this study, we consolidate the causality of loss of MAPKAPK5 function and further delineate the molecular and phenotypic spectrum associated with this new ultra-rare neurodevelopmental syndrome., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Adult-onset leukodystrophies though individually rare are not uncommon. This group includes several disorders with isolated adult presentations, as well as several childhood leukodystrophies with attenuated phenotypes that present at a later age. Misdiagnoses often occur due to the clinical and radiological overlap with common acquired disorders such as infectious, immune, inflammatory, vascular, metabolic, and toxic etiologies. Increased prevalence of non-specific white matter changes in adult population poses challenges during diagnostic considerations. Clinico-radiological spectrum and molecular landscape of adult-onset leukodystrophies have not been completely elucidated at this time. Diagnostic approach is less well-standardized when compared to the childhood counterpart. Absence of family history and reduced penetrance in certain disorders frequently create a dilemma. Comprehensive evaluation and molecular confirmation when available helps in prognostication, early initiation of treatment in certain disorders, enrollment in clinical trials, and provides valuable information for the family for reproductive counseling. In this review article, we aimed to formulate an approach to adult-onset leukodystrophies that will be useful in routine practice, discuss common adult-onset leukodystrophies with usual and unusual presentations, neuroimaging findings, recent advances in treatment, acquired mimics, and provide an algorithm for comprehensive clinical, radiological, and genetic evaluation that will facilitate early diagnosis and consider active treatment options when available. A high index of suspicion, awareness of the clinico-radiological presentations, and comprehensive genetic evaluation are paramount because treatment options are available for several disorders when diagnosed early in the disease course., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Muthusamy, Sivadasan, Dixon, Sudhakar, Thomas, Danda, Wszolek, Wierenga, Dhamija and Gavrilova.)

Laser ablation for treatment of hypothalamic hamartoma (HH) is a minimally invasive and effective technique used to destroy hamartomatous tissue and disconnect it from the functioning brain. Currently, the gold standard to evaluate the amount of tissue being "burned" is the use of heat maps during the ablation procedure. However, these maps have low spatial resolution and can be misleading in terms of extension of the tissue damage. The aim of this study is to use different MRI sequences immediately after each laser ablation and correlate the extension of signal changes with the volume of malacic changes in a long-term follow-up scan. During the laser ablation procedure, we imaged the hypothalamic region with high-resolution axial diffusion-weighted images (DWI) and T2-weighted images (T2WI) after each ablation. At the end of the procedure, we also added a post-contrast T1-weighted image (T1WI) of the same region. We then correlated the product of the maximum diameters on axial showing signal changes (acute oedema on T2WI, DWI restriction rim, DWI hypointense core and post-contrast T1WI rim) with the product of the maximum diameters on axial T2WI of the malacic changes in the follow-up scan, both as a fraction of the total area of the hamartoma. The area of the hypointense core on DWI acquired immediately after the laser ablation statistically correlated better with the final area of encephalomalacia, while the T2WI, hyperintense oedema, DWI rim and T1WI rim of enhancement tended to overestimate the encephalomalacic damage. In conclusion, the use of intraoperative sequences (in particular DWI) during laser ablation can give surgeons valuable information in real time about the effective heating damage on the hamartomatous tissue, with better spatial resolution in comparison to the thermal maps.

Background and Objectives: Sevoflurane and desflurane virtually equally dissolve in blood gases, yet current research suggests that desflurane helps in a quick return of airway reflex than sevoflurane however the return of cognitive activity fluctuates greatly. In order to compare the lengths of time required to recover after sevoflurane and desflurane anesthesia, the current research was conducted., Materials and Methods: Current study was randomized that included 100 subjects who were posted for cholecystectomy (elective). Only adult and non-obese subjects were included in the study. The intended anesthetic agents sevoflurane and desflurane were utilized in the study and all the protocols were followed for the surgery. After the end of the surgery, tests for regaining cognitive function and airway reflexes were carried out, and different time intervals were recorded. The values were recorded and compared for the variances while considering the P < 0.05 as significant., Results: The mean T1 was 8.19 ± 3.28 min for sevoflurane and was 5.82 ± 4.02 min. There was no significant variance between the two agents for the T1, 2 ( P = 0.013 and 0.110 respectively). After the inhalation anesthetics ceased at T1, desflurane patients responded to verbal commands more quickly than sevoflurane patients (5.824.02 vs. 8.193.28 min). The SOMCT and swallowing test were similarly completed more quickly by desflurane-treated patients than by sevoflurane-treated patients (T3VST4) (13.693.37 vs. 10.024.86 min, P = 0.008 and (14.094.30 vs. 9.824.50 min, P 0.001, respectively). For the T3, 4-time intervals, there was a significant difference between the sevoflurane and desflurane groups., Conclusion: Desflurane causes patients to recover more quickly from laparoscopic cholecystectomy under controlled circumstances than sevoflurane does., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

Aim: The purpose of the study is to compare and evaluate the efficacy of different root canal irrigants-100, 75, 50, and 25% neem extract, 100, 75, 50, and 25% apple cider vinegar (ACV), a combination of 5.25% sodium hypochlorite (NaOCl) and 17% ethylenediaminetetraacetic acid (EDTA), and saline on smear layer removal using a scanning electron microscope (SEM)., Materials and Methods: A total of 80 freshly extracted single-rooted teeth were collected and divided into 10 groups-group I: normal saline (negative control), group II: NaOCl with EDTA (positive control), group III: 100% neem extract, group IV: 75% neem extract, group V: 50% neem extract, group VI: 25% neem extract, group VII: 100% ACV, group VIII: 75% ACV, group IX: 50% ACV, and group X: 25% ACV. The samples were irrigated with a specific group of irrigants, then split in a longitudinal axis and processed for analysis in an SEM. Microphotographs were obtained and scored according to Torabinejad et al., Results: Microphotographs were assessed and showed that 100% neem extract was similar to NaOCl with EDTA, followed by 75% neem extract and 100% ACV., Conclusion: This study showed that 100% neem extract removed the smear layer, similar to the NaOCl with EDTA., How to Cite This Article: Sudhakar S, Gupta N, Ghambir N, et al. Comparative Evaluation of Intracanal Smear Layer Removal by Different Root Canal Irrigants: A Scanning Electron Microscope Study. Int J Clin Pediatr Dent 2023;16(4):633-638., Competing Interests: Source of support: Nil Conflict of interest: Dr Nidhi Gupta is associated as the National Editorial Board member of this journal and this manuscript was subjected to this journal's standard review procedures, with this peer review handled independently of this editorial board member and his research group., (Copyright © 2023; The Author(s).)

Congenital melanocytic naevus (CMN) syndrome, previously termed neurocutaneous melanosis, is a rare disease caused by postzygotic mosaic mutations occurring during embryogenesis in precursors of melanocytes. The severity of neurological manifestations in CMN patients is related to central nervous system abnormalities found at magnetic resonance imaging. The association between CMN and Dandy-Walker malformation (DWM) has been described in the literature, but recent advances in imaging and genetics lead to diagnostic criteria revision. In this paper, we aim to re-evaluate the proposed association by reviewing the available literature and present a patient with CMN and a large posterior fossa cyst., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objectives: Birk-Landau-Perez syndrome is a genetic disorder caused by biallelic pathogenic variants in SLC30A9 presenting with a complex movement disorder, developmental regression, oculomotor abnormalities, and renal impairment. It has previously been reported in 2 families. We describe the clinical phenotype of 8 further individuals from 4 unrelated families with SLC30A9 -related disease., Method: Following detailed clinical phenotyping, 1 family underwent research whole-genome sequencing (WGS), 1 research whole-exome sequencing, and 2 diagnostic WGS. Variants of interest were assessed for pathogenicity using in silico prediction tools, homology modeling, and, where relevant, sequencing of complementary DNA (cDNA) for splicing effect., Results: In 2 unrelated families of Pakistani origin (1 consanguineous and 1 not), the same homozygous missense variant in SLC30A9 (c.1253G>T, p.Gly418Val) was identified. Family 1 included 2 affected brothers, and family 2 one affected boy. In family 3, also consanguineous, there were 4 affected siblings homozygous for the variant c.1049delCAG, pAla350del. The fourth family was nonconsanguineous: the 1 affected individual was compound heterozygous for c.1083dup, p.Val362Cysfs*5, and c.1413A>G, p.Ser471=. Despite phenotypic variability between the 4 families, all affected patients manifested with a progressive hyperkinetic movement disorder, associated with oculomotor apraxia and ptosis. None had evidence of severe renal impairment. For the novel missense variant, the conformation of the loop domain and packing of transmembrane helices are likely to be disrupted based on structure modeling. Its presence in 2 unrelated Pakistani families suggests a possible founder variant. For the synonymous variant p.Ser471=, an effect on splicing was confirmed through cDNA analysis., Discussion: Pathogenic variants in SLC30A9 cause a progressive autosomal recessive neurologic syndrome associated with a complex hyperkinetic movement disorder. Our report highlights the expanding disease phenotype, which can present with a wider spectrum of severity than has previously been recognized., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Paucity of efficient probes and small molecule ligands that can distinguish different G-quadruplex (GQ) topologies poses challenges not only in understanding their basic structure but also in targeting an individual GQ form from others. Alternatively, G-rich sequences that harbour unique chimeric structural motifs ( e.g. , GQ-duplex or GQ-hairpin junctions) are perceived as new therapeutic hotspots. In this context, the epidermal growth factor receptor (EGFR) gene, implicated in many cancers, contains a 30 nucleotide G-rich segment in the promoter region, which adopts in vitro two unique architectures each composed of a GQ topology (parallel and hybrid-type) juxtaposed with a hairpin domain. Here, we report the use of a novel dual-app probe, C5-trifluoromethyl benzofuran-modified 2'-deoxyuridine (TFBF-dU), in the systematic analysis of EGFR GQs and their interaction with small molecules by fluorescence and 19 F NMR techniques. Notably, distinct fluorescence and 19 F NMR signals exhibited by the probe enabled the quantification of the relative population of random, parallel and hybrid-type GQ structures under different conditions, which could not be obtained by conventional CD and 1 H NMR techniques. Using the fluorescence component, we quantified ligand binding properties of GQs, whereas the 19 F label enabled the assessment of ligand-induced changes in GQ dynamics. Studies also revealed that mutations in the hairpin domain affected GQ formation and stability, which was further functionally verified in polymerase stop assay. We anticipate that these findings and useful properties of the nucleoside probe could be utilized in designing and evaluating binders that jointly target both GQ and hairpin domains for enhanced selectivity and druggability., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Ribonucleoproteins (RNPs) comprise one or more RNA and protein molecules that interact to form a stable complex, which commonly involves conformational changes in the more flexible RNA components. Here, we propose that Cas12a RNP assembly with its cognate CRISPR RNA (crRNA) guide instead proceeds primarily through Cas12a conformational changes during binding to more stable, prefolded crRNA 5' pseudoknot handles. Phylogenetic reconstructions and sequence and structure alignments revealed that the Cas12a proteins are divergent in sequence and structure while the crRNA 5' repeat region, which folds into a pseudoknot and anchors binding to Cas12a, is highly conserved. Molecular dynamics simulations of three Cas12a proteins and their cognate guides revealed substantial flexibility for unbound apo-Cas12a. In contrast, crRNA 5' pseudoknots were predicted to be stable and independently folded. Limited trypsin hydrolysis, differential scanning fluorimetry, thermal denaturation, and CD analyses supported conformational changes of Cas12a during RNP assembly and an independently folded crRNA 5' pseudoknot. This RNP assembly mechanism may be rationalized by evolutionary pressure to conserve CRISPR loci repeat sequence, and therefore guide RNA structure, to maintain function across all phases of the CRISPR defense mechanism., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The human dopaminergic system is vital for a broad range of neurological processes, including the control of voluntary movement. Here we report a proband presenting with clinical features of dopamine deficiency: severe infantile parkinsonism-dystonia, characterised by frequent oculogyric crises, dysautonomia and global neurodevelopmental impairment. CSF neurotransmitter analysis was unexpectedly normal. Triome whole-genome sequencing revealed a homozygous variant (c.110C>A, (p.T37K)) in DRD1 , encoding the most abundant dopamine receptor (D 1 ) in the central nervous system, most highly expressed in the striatum. This variant was absent from gnomAD, with a CADD score of 27.5. Using an in vitro heterologous expression system, we determined that DRD1 -T37K results in loss of protein function. Structure-function modelling studies predicted reduced substrate binding, which was confirmed in vitro. Exposure of mutant protein to the selective D 1 agonist Chloro APB resulted in significantly reduced cyclic AMP levels. Numerous D 1 agonists failed to rescue the cellular defect, reflected clinically in the patient, who had no benefit from dopaminergic therapy. Our study identifies DRD1 as a new disease-associated gene, suggesting a crucial role for the D 1 receptor in motor control.