Efficacy of anti-suppression therapy in improving binocular vision in children with small-angle Esotropia

Purpose: To evaluate the efficacy of anti-suppression exercises in children with small-angle esotropia in achieving binocular vision. Methods: A retrospective review of patients aged 3–8 years who underwent anti-suppression exercises for either monocular or alternate suppression between January 2016 and December 2021 was conducted. Patients with esotropia less than 15 prism diopters (PD) and visual acuity ≥ 6/12 were included. Patients with previous intra-ocular surgery or less than three-month follow-up were excluded. Success was defined as the development of binocular single vision (BSV) for distance, near, or both (measured clinically with either the 4 prism base out test or Worth four dot test) and maintained at two consecutive visits. Qualified success was defined as the presence of diplopia response for both distance and near. Additionally, improvement in near stereo acuity was measured using the Stereo Fly test. Results: Eighteen patients with a mean age of 5.4 ± 1.38 years (range 3–8 years) at the time of initiation of exercises were included in the study. The male female ratio was 10:8. The mean best corrected visual acuity was 0.18 LogMAR unit(s) and the mean spherical equivalent was +3.8 ± 0.14 diopters (D). The etiology of the esotropia was fully accommodative refractive esotropia (8), microtropia (1), post–operative infantile esotropia (4), partially accommodative esotropia (1), and post-operative partially accommodative esotropia (4). Patients received either office-based, home-based, or both modes of treatment for an average duration of 4.8 months (range 3–8). After therapy, BSV was achieved for either distance or near in 66.6 % of patients (95 % CI = 40.03–93.31 %). Binocular single vision for both distance and near was seen in 50 % of children. Qualified success was observed in 38.46% of patients. Persistence of suppression was observed in one patient (5.5 %)... (AU)

Comparison of the Clinical Efficacy of Rituximab Infusion and Dexamethasone-Cyclophosphamide Pulse Therapy and Their Effect on Serum Th1, Th2, and Th17 Cytokines in Pemphigus Vulgaris-A Prospective, Nonrandomized, Comparative Pilot Study.

Background: Rituximab infusion and dexamethasone-cyclophosphamide pulse (DCP) are the two most popular regimens used in pemphigus vulgaris (PV) in India. Objective: The present study compared the clinical efficacy of rituximab and DCP in Indian PV patients and their effects on serum Th1,2, and 17 cytokine levels. Materials and Methods: A total of 37 patients received DCP (Group A, n = 22) or rituximab (Group B, rheumatoid arthritis protocol (n = 15)) as per patients' preference. They were monitored for clinical response, adverse events (AEs), changes in serum anti-desmoglein-1,3 antibody titers and Th1,2 and 17 cytokine levels at baseline and weeks 20 and 52. Results: The proportion of patients attaining disease control, remission, and relapse in groups A and B were 82% and 93%; 73% and 93%; and 27% and 50%, respectively, after a median duration of 2 months each for disease control; 4 and 4.5 months for remission; and 5 and 7 months for relapse post remission. The musculoskeletal AEs were the highest in the two groups. Significant and comparable decreases in anti-dsg1 and 3 titers from baseline to weeks 20 and 52 were observed in both groups. Th1 and Th17 cytokine levels decreased, while Th2 cytokines increased post-treatment in both groups. However, no correlation was found between change in body surface area of involvement by PV and anti-dsg titers and cytokine levels before and after therapy in both groups. Conclusion: Comparable clinical efficacy between DCP and rituximab was observed.

Hazard identification of endocrine-disrupting carcinogens (EDCs) in relation to cancers in humans.

Endocrine disrupting chemicals or carcinogens have been known for decades for their endocrine signal disruption. Endocrine disrupting chemicals are a serious concern and they have been included in the top priority toxicants and persistent organic pollutants. Therefore, researchers have been working for a long time to understand their mechanisms of interaction in different human organs. Several reports are available about the carcinogen potential of these chemicals. The presented review is an endeavor to understand the hazard identification associated with endocrine disrupting carcinogens in relation to the human body. The paper discusses the major endocrine disrupting carcinogens and their potency for carcinogenesis. It discusses human exposure, route of entry, carcinogenicity and mechanisms. In addition, the paper discusses the research gaps and bottlenecks associated with the research. Moreover, it discusses the limitations associated with the analytical techniques for detection of endocrine disrupting carcinogens.

Engineered lignocellulosic based biochar to remove endocrine-disrupting chemicals: Assessment of binding mechanism.

The safety and health of aquatic organisms and humans are threatened by the increasing presence of pollutants in the environment. Endocrine disrupting chemicals are common pollutants which affect the function of endocrine and causes adverse effects on human health. These chemicals can disrupt metabolic processes by interacting with hormone receptors upon consumptions by humans or aquatic species. Several studies have reported the presence of endocrine disrupting chemicals in waterbodies, food, air and soil. These chemicals are associated with increasing occurrence of obesity, metabolic disorders, reproductive abnormalities, autism, cancer, epigenetic variation and cardiovascular risk. Conventional treatment processes are expensive, not environment friendly and unable to achieve complete removal of these harmful chemicals. In recent years, biochar from different sources has gained a considerable interest due to their adsorption efficiency with porous structure and large surface areas. biochar derived from lignocellulosic biomass are widely used as sustainable catalysts in soil remediation, carbon sequestration, removal of organic and inorganic pollutants and wastewater treatment. This review conceptualizes the production techniques of biochar from lignocellulosic biomass and explores the functionalization and interaction of biochar with endocrine-disrupting chemicals. This review also identifies the further needs of research. Overall, the environmental and health risks of endocrine-disrupting chemicals can be dealt with by biochar produced from lignocellulosic biomass as a sustainable and prominent approach.

Assessing the reliability of tele-refraction for real time consultation with a remote optometrist.

INTRODUCTION: Uncorrected refractive errors pose a significant challenge globally, particularly in remote regions of low-middle income countries where access to optometric care is often limited. Telerefraction, which involves refraction by a trained technician followed by real-time consultation with remote optometrist, is a promising approach for such remote settings. This study aimed to evaluate the accuracy of this model. METHODS: This prospective study, conducted in New Delhi, compared tele-refraction to in-person examinations. Trained technicians used a simple device, Click-check, to perform objective refraction and a tele-refraction platform to enter the findings of objective refraction. Final prescription was made after consulting a remote optometrist on that platform. Masked face-to-face optometrists served as the gold standard. The study involved refraction in 222 patients and 428 eyes. RESULTS: Tele-refraction demonstrated a strong agreement with in-person optometry, achieving 84.6% in spherical correction and 81% conformity in spherical equivalent. The mean difference of spherical equivalent between the two arms was only 0.11 D. The consultation with a remote optometrist improved conformity of spherical equivalent by 14.8% over objective refraction. 82 percent eyes matched in best corrected visual acuity and 92 percent were within 0.1 logMAR difference. For cylindrical axis, 74% eye were within acceptable 10 degrees of difference. The mismatch amongst the individual trained technicians, in terms of difference between the tele-refraction arm and the face-to face optometrist arm was found to be significant for cylindrical axis and not for spherical power and spherical equivalent. CONCLUSION: Our study found tele-refraction by a trained technician comparable to refraction done by face-to-face optometrist. Tele-refraction, coupled with remote optometrist guidance can address the optometry resource gap in underserved areas. Thus, this model offers a transformative approach to enhancing the accessibility and quality of eye care services, which can significantly contribute to our efforts in achieving the global targets set by the World Health Organization for effective refractive error coverage. More standardized training for these technicians on ClickCheckTM for detecting the cylindrical axis with better accuracy, can improve this model further.

Phytochemical profiling, antioxidant potential and cytotoxic activity of Sargassum prismaticum extracts: implications for therapeutic applications.

Seaweeds are sources of bioactive compounds with medicinal properties, which make them attractive candidates for natural therapeutic agents. Marine brown algae are known to possess anti-inflammatory, hepatoprotective, anticancer properties, etc. Present study was carried out to identify the phytochemical constituents, antioxidant and cytotoxic activities of Sargassum prismaticum in two different solvents viz., chloroform and methanol. Chloroform was found to be the superior solvent for phenol and flavonoid extraction. Antioxidant activity was determined using DPPH and ABTS assays; however, the methanolic extract demonstrated better antioxidant potential. The highest cell cytotoxicity with an IC50 value of 7.6 ± 0.02 µg/mL was observed in methanolic extract, while the chloroform extract had an IC50 value of 9.6 ± 0.03 µg/mL against U937 cell line. These finding suggest that Sargassum prismaticum possesses potent antioxidant and cytotoxic properties, making it a potential candidate for further study as a novel antioxidant drug source.

Noncovalent synthesis of homo and hetero-architectures of supramolecular polymers via secondary nucleation.

The synthesis of supramolecular polymers with controlled architecture is a grand challenge in supramolecular chemistry. Although living supramolecular polymerization via primary nucleation has been extensively studied for controlling the supramolecular polymerization of small molecules, the resulting supramolecular polymers have typically exhibited one-dimensional morphology. In this report, we present the synthesis of intriguing supramolecular polymer architectures through a secondary nucleation event, a mechanism well-established in protein aggregation and the crystallization of small molecules. To achieve this, we choose perylene diimide with 2-ethylhexyl chains at the imide position as they are capable of forming dormant monomers in solution. Activating these dormant monomers via mechanical stimuli and hetero-seeding using propoxyethyl perylene diimide seeds, secondary nucleation event takes over, leading to the formation of three-dimensional spherical spherulites and scarf-like supramolecular polymer heterostructures, respectively. Therefore, the results presented in this study propose a simple molecular design for synthesizing well-defined supramolecular polymer architectures via secondary nucleation.

Emotion recognition for human-computer interaction using high-level descriptors.

Recent research has focused extensively on employing Deep Learning (DL) techniques, particularly Convolutional Neural Networks (CNN), for Speech Emotion Recognition (SER). This study addresses the burgeoning interest in leveraging DL for SER, specifically focusing on Punjabi language speakers. The paper presents a novel approach to constructing and preprocessing a labeled speech corpus using diverse social media sources. By utilizing spectrograms as the primary feature representation, the proposed algorithm effectively learns discriminative patterns for emotion recognition. The method is evaluated on a custom dataset derived from various Punjabi media sources, including films and web series. Results demonstrate that the proposed approach achieves an accuracy of 69%, surpassing traditional methods like decision trees, Naïve Bayes, and random forests, which achieved accuracies of 49%, 52%, and 61% respectively. Thus, the proposed method improves accuracy in recognizing emotions from Punjabi speech signals.

An Unusual Case of Symptomatic Isolated Lingual Cysticercosis: Clinical Suspicion Helped Prevent Disseminated Disease.

Intraorally, cysticercosis is regarded as uncommon and a diagnostic challenge. Here, we report a diagnostic conundrum of an unusual case of innocuous appearing lesion on the tongue presenting as moderately tender swelling finally diagnosed as lingual cysticercosis, based on USG (Ultrasound), CT (Computed Tomography) findings and characteristic histopathologic features.

Biomechanical analysis and comparison between 'Zeta' miniplate design and conventional miniplate system for fixation of fracture segments in transition zone of parasymphysis body region of mandible - an in vitro study.

The parasymphysis area of the mandible is highly dynamic because it is subjected to both occlusal and muscular forces. As a result, the fractures in this transition zone have a special pattern, posing a challenge for surgeons whether to use one miniplate versus two miniplates, as per Champy's recommendations. The commonest complication resulting to treat this area is mental nerve paraesthesia due to the dissection and stretching of the nerve. Hence, an in vitro research study of a newly designed 'Zeta' miniplate is performed, to evaluate the biomechanical behaviour using finite element (FE) analysis and biomechanical analysis along with a comparison study with the conventional miniplate configurations. The results showed that the Zeta miniplate produces the lowest stresses 17.511 MPa and the least total structural deformation of 0.0011 mm after applying the maximum occlusal bite force. On application of torsional load, total structural deformation was 0.0004 mm and von Mises (VM) stress value was 0.24 MPa which was lowest when compared with the two miniplate system. Hence, the newly developed Zeta miniplate is superior in terms of stability. Another benefit of its design is that it helps in preventing mental nerve paraesthesia and tooth root damage while fixing and stabilising the fractured bony segments.

Unified deep learning models for enhanced lung cancer prediction with ResNet-50-101 and EfficientNet-B3 using DICOM images.

Significant advancements in machine learning algorithms have the potential to aid in the early detection and prevention of cancer, a devastating disease. However, traditional research methods face obstacles, and the amount of cancer-related information is rapidly expanding. The authors have developed a helpful support system using three distinct deep-learning models, ResNet-50, EfficientNet-B3, and ResNet-101, along with transfer learning, to predict lung cancer, thereby contributing to health and reducing the mortality rate associated with this condition. This offer aims to address the issue effectively. Using a dataset of 1,000 DICOM lung cancer images from the LIDC-IDRI repository, each image is classified into four different categories. Although deep learning is still making progress in its ability to analyze and understand cancer data, this research marks a significant step forward in the fight against cancer, promoting better health outcomes and potentially lowering the mortality rate. The Fusion Model, like all other models, achieved 100% precision in classifying Squamous Cells. The Fusion Model and ResNet-50 achieved a precision of 90%, closely followed by EfficientNet-B3 and ResNet-101 with slightly lower precision. To prevent overfitting and improve data collection and planning, the authors implemented a data extension strategy. The relationship between acquiring knowledge and reaching specific scores was also connected to advancing and addressing the issue of imprecise accuracy, ultimately contributing to advancements in health and a reduction in the mortality rate associated with lung cancer.

Endosomal escape: A bottleneck for LNP-mediated therapeutics.

Lipid nanoparticles (LNPs) have recently emerged as a powerful and versatile clinically approved platform for nucleic acid delivery, specifically for mRNA vaccines. A major bottleneck in the field is the release of mRNA-LNPs from the endosomal pathways into the cytosol of cells where they can execute their encoded functions. The data regarding the mechanism of these endosomal escape processes are limited and contradicting. Despite extensive research, there is no consensus regarding the compartment of escape, the cause of the inefficient escape and are currently lacking a robust method to detect the escape. Here, we review the currently known mechanisms of endosomal escape and the available methods to study this process. We critically discuss the limitations and challenges of these methods and the possibilities to overcome these challenges. We propose that the development of currently lacking robust, quantitative high-throughput techniques to study endosomal escape is timely and essential. A better understanding of this process will enable better RNA-LNP designs with improved efficiency to unlock new therapeutic modalities.

Recovery of polarization entanglement in partially coherent photonic qubits.

Partially coherent photonic qubits, owing to their robustness in propagation through random media compared to fully coherent qubits, find applications in free-space communication, quantum imaging, and quantum sensing. However, the reduction of spatial coherence degrades entanglement in qubits, adversely affecting entanglement-based applications. We report the recovery of entanglement in the partially coherent photonic qubits generated using a spontaneous parametric downconversion process despite retaining their multimode nature. This study utilizes an electron multiplying charge-coupled device (EMCCD) to perform coincidence measurements, eliminating the need for raster scanning of single-pixel detectors, which simplifies optical alignment, enhances precision, and reduces time consumption. We demonstrate that the size of apertures used to select biphotons substantially impacts the visibility and S-parameter of polarization-entangled partially coherent qubits. The entanglement is recovered with partial spatial coherence properties by choosing small sizes of the apertures in the captured image plane. This study could help in the advancement of free-space quantum communication, quantum imaging, and quantum metrology.

i-shaped antibody engineering enables conformational tuning of biotherapeutic receptor agonists.

The ability to leverage antibodies to agonize disease relevant biological pathways has tremendous potential for clinical investigation. Yet while antibodies have been successful as antagonists, immune mediators, and targeting agents, they are not readily effective at recapitulating the biology of natural ligands. Among the important determinants of antibody agonist activity is the geometry of target receptor engagement. Here, we describe an engineering approach inspired by a naturally occurring Fab-Fab homotypic interaction that constrains IgG in a unique i-shaped conformation. i-shaped antibody (iAb) engineering enables potent intrinsic agonism of five tumor necrosis factor receptor superfamily (TNFRSF) targets. When applied to bispecific antibodies against the heterodimeric IL-2 receptor pair, constrained bispecific IgG formats recapitulate IL-2 agonist activity. iAb engineering provides a tool to tune agonist antibody function and this work provides a framework for the development of intrinsic antibody agonists with the potential for generalization across broad receptor classes.

Nanoemulsion potentiates the anti-cancer activity of Myricetin by effective inhibition of PI3K/AKT/mTOR pathway in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is a heterogeneous tumor with a poor prognosis and high metastatic potential, resulting in poor clinical outcomes, necessitating investigation to devise effective therapeutic strategies. Multiple studies have substantiated the anti-cancer properties of the naturally occurring flavonoid "Myricetin" in various malignancies. However, the therapeutic application of Myricetin is impeded by its poor water solubility and low oral bioavailability. To overcome this limitation, we aimed to develop nanoemulsion of Myricetin (Myr-NE) and evaluate its advantage over Myricetin alone in TNBC cells. The nanoemulsion was formulated using Capryol 90 (oil), Tween 20 (surfactant), and Transcutol HP (co-surfactant). The optimized nano-formulation underwent an evaluation to determine its size, zeta potential, morphology, stability, drug encapsulation efficiency, and in vitro release properties. The anti-cancer activity of Myr-NE was further studied to examine its distinct impact on intracellular drug uptake, cell-viability, anti-tumor signaling, oxidative stress, clonogenicity, and cell death, compared with Myricetin alone in MDA-MB-231 (TNBC) cells. The in vitro drug release and intracellular drug uptake of Myricetin was significantly increased in Myr-NE formulation as compared to Myricetin alone. Moreover, Myr-NE exhibited significant inhibition of cell proliferation, clonogenicity, and increased apoptosis with ~ 2.5-fold lower IC50 as compared to Myricetin. Mechanistic investigation revealed that nanoemulsion augmented the anti-cancer efficacy of Myricetin, most likely by inhibiting the PI3K/AKT/mTOR pathway, eventually leading to enhanced cell death in TNBC cells. The study provides substantial experimental evidence to support the notion that the Myr-NE formulation has the potential to be an effective therapeutic drug for TNBC treatment.

A new onset drug induced diabetes mellitus presenting with diabetic ketoacidosis in a child undergoing treatment for B cell acute lymphoblastic leukemia. A case report and review of literature.

OBJECTIVES: Hyperglycemia is a known side effect of anticancer chemotherapeutic drugs. This entity known as drug-induced diabetes mellitus usually does not present with the development of diabetic ketoacidosis (DKA). We hereby report a case of drug induced diabetes mellitus in a child with acute leukemia presenting with DKA. CASE PRESENTATION: We report a case of a teenage boy diagnosed with B cell acute lymphoblastic leukemia and was started on induction phase chemotherapy as per the Indian Collaborative Childhood Leukemia group (ICICLe) acute lymphoblastic leukemia-14 protocol. On day 12 of the induction phase, he developed hyperglycemia and presented to us with severe diabetic ketoacidosis (DKA). Serum anti glutamic acid decarboxylase 65 antibody levels were negative with low serum C peptide levels. Initially, the possibility of drug-induced acute pancreatitis was kept which was ruled out. Keeping the possibility of drug-induced hyperglycemia, the child was started on subcutaneous regular insulin which was titrated as per sugar records. Continuation of remaining chemotherapy was done by PEGylated L-asparaginase with titration of insulin as per home-based sugar records. Insulin requirement increased from 0.3 unit/kg/day to a maximum of 1 unit/kg/day during consolidation phase 1 with PEGylated L-asparaginase suggesting drug-induced hyperglycemia but subsequently insulin requirement decreased and insulin was stopped. CONCLUSIONS: Drug induced diabetes mellitus can present as DKA during induction phase of acute lymphoblastic leukemia (ALL) chemotherapy. A high index of suspicion and close monitoring are required. The insulin requirements in these patients can be very fluctuant and may become nil during the course of treatment.

Clear cell oral squamous cell carcinoma as a diagnostic conundrum: report of 2 rare cases.

The occurrence of clear cell histologic sub-type of oral squamous cell carcinoma in the oral cavity is a distinct and exceedingly rare entity exhibiting aggressive behavior. To date, only 10 cases have been published in the literature. We describe 2 extremely rare cases, both presenting with swelling and ulcerated nodule-like proliferative growth in the mandible. Microscopically, sheets and lobules of neoplastic squamous epithelial cells showing clear cell differentiation were appreciated in both patients. Periodic acid-Schiff and mucicarmine revealed negative staining. Immunohistochemical (IHC) analysis for antibody for renal cell tumor marker CD 10 was immune-negative. The malignant clear cells in both cases showed intense positive reactions with IHC markers pan-cytokeratin and epithelial membrane antigen, confirming the diagnosis as a clear cell variant of oral squamous cell carcinoma (CCOSCC). The first patient was unwilling for treatment and eventually died within 2 months of the diagnosis. In the second patient, right hemi-mandibulectomy with level 1A and 1B lymph nodes was performed. Adjuvant chemotherapy with low-dose methotrexate was initiated. Follow-up after 2 months of surgery was uneventful. Current rare reports emphasize the significance of prompt and extensive diagnostic work-up of clear cell neoplasms, as the CCOSCC may be fatal.

The immunostimulatory nature of mRNA lipid nanoparticles.

mRNA-Lipid nanoparticles (LNPs) are at the forefront of global medical research. With the development of mRNA-LNP vaccines to combat the COVID-19 pandemic, the clinical potential of this platform was unleashed. Upon administering 16 billion doses that protected billions of people, it became clear that a fraction of them witnessed mild and in some cases even severe adverse effects. Therefore, it is paramount to define the safety along with the therapeutic efficacy of the mRNA-LNP platform for the successful translation of new genetic medicines based on this technology. While mRNA was the effector molecule of this platform, the ionizable lipid component of the LNPs played an indispensable role in its success. However, both of these components possess the ability to induce undesired immunostimulation, which is an area that needs to be addressed systematically. The immune cell agitation caused by this platform is a two-edged sword as it may prove beneficial for vaccination but detrimental to other applications. Therefore, a key challenge in advancing the mRNA-LNP drug delivery platform from bench to bedside is understanding the immunostimulatory behavior of these components. Herein, we provide a detailed overview of the structural modifications and immunogenicity of synthetic mRNA. We discuss the effect of ionizable lipid structure on LNP functionality and offer a mechanistic overview of the ability of LNPs to elicit an immune response. Finally, we shed some light on the current status of this technology in clinical trials and discuss a few challenges to be addressed to advance the field.

Evaluation of antihypertensive activity and molecular docking analysis of Padina boergesenii extract.

INTRODUCTION: Antihypertensive drugs that are chemically synthesized usually tend to initiate different health complications. The quest for bioactive molecules to create novel medicines has focused on Marine resources like seaweeds. These molecules can furnish a positive probability for patients to gain benefits from these natural substances. METHODS: This study aims to identify phytoconstituents present in brown seaweed-Padina boergesenii. Five different solvents were used to prepare extracts and their antioxidant activity as well as antihypertensive activity was evaluated. Phytoconstituents were identified using LC-MS/MS, and subjected to molecular interaction against ACE enzyme. RESULTS: The 70% ethanolic extract exhibited the highest total phenolic content (TPC), significant radical scavenging activity and concentration dependent Angiotensin Converting Enzyme (ACE) inhibition activity. LC-MS/MS analysis confirmed the presence of bioactive compounds from which 7,8 dihydroxycoumarin had the highest affinity against ACE enzyme in molecular docking study. CONCLUSION: These findings advocate that Padina boergesenii can be a potential source for developing novel antihypertensive therapeutic drug(s) and could pave the way for evolving effective and safe remedies from natural resources.