Physical Rehabilitation Using Oromotor Stimulation, Manual Airway Clearance Technique, Positioning, and Tactile and Kinaesthetic Stimulation (PROMPT) Protocol in Low-Birth-Weight Triplets With Neonatal Respiratory Distress: A Case Series.

Neonatal respiratory distress syndrome (RDS), a severe respiratory illness that is likely to affect preterm newborns especially those who were born preterm with low birth weight (LBW) or multiple births, is one of the complications that preterm babies are likely to develop. Physical Rehabilitation using Oromotor Stimulation, Manual Airway Clearance Technique, Positioning, and Tactile and Kinaesthetic Stimulations (PROMPT) is the intervention followed in this study to determine its effectiveness in the treatment of RDS in LBW triplets. The PROMPT protocol involves interventions such as manually promoting the airway, positioning, oral motor stimulation, and tactile and kinesthetic stimulation. The study examined triplets of similar weight, 1.23g, 1.36g, and 1.18g, at birth. Thus, all known triplets were suffering from the symptoms of RDS like fast breathing and grunting. They were born via premature delivery at 30+5 weeks of pregnancy. Chest X-rays were used as a diagnostic tool for assessing RDS. At the same time, the PROMPT protocol was administered and significant improvements were seen in respiratory health and there was reduced use of mechanical ventilation. The PROMPT protocol shows how effectively an organized method can be applied to treat RDS in LBW triplets.

A Pioneer in Revolutionizing Physiotherapy in India: Dr. M. G. Mokashi's Journey of Compassion, Innovation, and Dedication.

Dr. Madhav Gajanan Mokashi is a remarkable individual in physiotherapy, and he is celebrated for his exceptional blend of educational and clinical excellence. His innovative research and influential roles in prominent conferences have shaped the physiotherapy landscape in India. Beyond his professional achievements, Dr. Mokashi has touched countless lives with his unique approach, integrating spiritual wisdom with practical expertise to foster an atmosphere of empathy and respect. His journey, marked by significant health challenges and an amputation, stands as a testament to his unwavering dedication, resilience, and sense of humor. Dr. Mokashi's legacy extends beyond his professional milestones; it resonates deeply in the hearts of those he has mentored and inspired. This review honours his enduring impact and the profound inspiration he offers to the next generation of healthcare professionals.

Reviving Movement and Stability: A Case Series on Different Innovative Rehabilitation Strategies Post-anterior Cruciate Ligament Reconstruction.

Injuries to the anterior cruciate ligament (ACL) are frequent and can seriously impair stability and mobility. This study examines rehabilitation outcomes in four patients following ligament reconstruction. Four patients who underwent ACL reconstruction and received different physiotherapy protocols, namely, "Oxford Knee Services," "Mass General Brigham," "Fowler Kennedy Sports Medicine," and "Schlechter Protocol of Youth Sports and Ortho," were included. The study aimed to identify the most effective rehabilitation approach. Demographic data, injury details, clinical examinations, and preoperative investigations were presented. Outcome measures included pain scores, range of motion (ROM), muscle strength, and functional assessments. All the patients showed improvements, but the rate of progress varied. Patient 3 achieved the best results in the ROM, muscle strength, and functional measures. This suggests that individual factors and rehabilitation protocols might influence outcomes. This study highlights the varying impacts of different rehabilitation protocols on the recovery outcomes of the patients' post-ACL reconstruction. Despite all patients showing improvements in pain reduction, ROM, muscle strength, and functional capabilities, the rate of progress and the degree of improvement differed notably among them.

Salivaomics in head and neck cancer.

Salivaomics is a promising method for the early detection and monitoring of head and neck cancer (HNC). By analyzing salivary proteomics, RNA, and DNA, it identifies biomarkers that distinguish HNC patients from healthy individuals. Saliva's non-invasive, easily collectible nature and affordability make it an advantageous screening tool. Multiomics approaches, which explore genetic mutations, gene expression patterns, protein profiles, and metabolite levels, provide a comprehensive molecular perspective that enhances clinical applicability. The approaches enhance the precision of diagnoses, enable the development and application of targeted therapies, and contribute to the overall advancement of personalized medicine. Despite its potential, larger-scale studies are essential for validating biomarkers, and assessing sensitivity, accuracy, and specificity in detecting HNC. This review highlights salivaomics' potential as a non-invasive, accessible biological sample for early disease detection in HNC and underscores the value of multiomics in advancing this research. Salivaomics offers significant insights into the underlying mechanisms of HNC, enabling the discovery of robust, non-invasive biomarkers for improved disease management.

Simple fluorochromic detection of chromium with ascorbic acid functionalized luminescent Bio-MOF-1.

The bioaccumulation of various heavy metals in the environment and agriculture is posing serious hazards to human health. Hexavalent chromium is one of the most encountered heavy metal pollutants. The routine monitoring of Cr(VI) via simple methods assumes great analytical significance in sectors like environmental safety, food quality, etc. This study reports a novel biocompatible and luminescent metal-organic framework (ascorbic acid functionalized Bio-MOF-1) based "Turn-on" nanoprobe for rapid and sensitive optical detection of Cr(VI). Bio-MOF-1 has been synthesized, functionalized with ascorbic acid (AA), and then comprehensively characterized for its key material properties. The presence of Cr(VI) results in the photoluminescence recovery of Bio-MOF-1/AA. Using the above approach, Cr(VI) is detected over a wide concentration range of 0.02 to 20 ng mL-1, with the limit of detection being 0.01 ng mL-1. The nanoprobe is capable of detecting Cr(VI) in real water as well as in some spiked food samples. Hence, the ascorbic acid functionalized Bio-MOF-1 nanoprobe is established as a potential on-field detection tool for Cr(VI).

Use of tryptic peptide MALDI mass spectrometry imaging to identify the spatial proteomic landscape of colorectal cancer liver metastases.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. CRC liver metastases (CRLM) are often resistant to conventional treatments, with high rates of recurrence. Therefore, it is crucial to identify biomarkers for CRLM patients that predict cancer progression. This study utilised matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to spatially map the CRLM tumour proteome. CRLM tissue microarrays (TMAs) of 84 patients were analysed using tryptic peptide MALDI-MSI to spatially monitor peptide abundances across CRLM tissues. Abundance of peptides was compared between tumour vs stroma, male vs female and across three groups of patients based on overall survival (0-3 years, 4-6 years, and 7+ years). Peptides were then characterised and matched using LC-MS/MS. A total of 471 potential peptides were identified by MALDI-MSI. Our results show that two unidentified m/z values (1589.876 and 1092.727) had significantly higher intensities in tumours compared to stroma. Ten m/z values were identified to have correlation with biological sex. Survival analysis identified three peptides (Histone H4, Haemoglobin subunit alpha, and Inosine-5'-monophosphate dehydrogenase 2) and two unidentified m/z values (1305.840 and 1661.060) that were significantly higher in patients with shorter survival (0-3 years relative to 4-6 years and 7+ years). This is the first study using MALDI-MSI, combined with LC-MS/MS, on a large cohort of CRLM patients to identify the spatial proteome in this malignancy. Further, we identify several protein candidates that may be suitable for drug targeting or for future prognostic biomarker development.

Microplastic pollution in high-altitude Nainital lake, Uttarakhand, India.

Microplastics (MPs) contamination has been reported in all environmental compartments, but very limited information is available at higher-altitude lakes. Nainital Lake, located at a high altitude in the Indian Himalayas, has various ecosystem services and is the major source of water for Nainital town, but the MP abundance is still unknown. This study presents the first evidence of the abundance and distribution of MP in Nainital Lake. Surface water and sediment samples were analysed from 16 different sites in and around the catchment area of Nainital Lake. The MP were observed in all the samples, and their abundance in surface water was 8.6-56.0 particles L-1 in the lake and 2.4-88.0 particles L-1 in hotspot sites. In the surface sediment, MP abundance ranged from 0.4-10.6 particles g-1, while in the hotspot sediment, the mean abundance was 0.6 ± 0.5 particles g-1. Fibers were the dominant MP, while 0.02-1 mm were the predominant size of MP particles. The results of chemical characterization showed the presence of six polymers, among which high-density polyethylene was the most abundant. The Polymer Hazard Index assessment classified the identified polymers as low-to high-risk categories, with a higher abundance of low- (polypropylene) and medium- (polyethylene)-risk polymers. Tourist activities and run-off catchments can be considered the major sources of MP, which can affect the ecosystem. Minimal concentrations of MP were observed in the tube well and drinking water, which depicts the direct risks to humans and, thus, the need for remedial measures to prevent MP contamination in drinking water. This study improves the knowledge of MP contamination in the higher-altitude freshwater lake, which can be the major pathway for the transport of MP to the rivers, and also emphasizes the need for waste management in Nainital town.

Unraveling Interaction of Rhenium-188 Microspheres with Primary Hepatic Cancer Cell: A Breakthrough Study.

Introduction: Hepatocellular carcinoma is a prevalent contributor to global mortality rates. The main palliative treatments are trans-arterial chemoembolization and selective intra-arterial radionuclide therapy. Methods: A novel freeze-dried nonradioactive microsphere kit formulation has been developed, and the behavior and therapeutic potential of 188Re microspheres have been assessed. The microspheres were labeled with fluorescein isothiocyanate (FITC) and 188ReO4-. The uptake of FITC microspheres by HepG2 cells was examined at various time intervals. The impact of 188Re microspheres on cell viability and the mode of cell death were investigated with HepG2 cells using MTT and Annexin FITC-V/propidium iodide (PI) apoptosis assay. Results: The labeling efficiency of microspheres was more than 99% with FITC and 188ReO4-. The maximum uptake of FITC microspheres by HepG2 cells was achieved at 6 h. The exposure to 188Re microspheres has shown a decrease in cellular viability from 77.81% ± 0.015% to 42.03% ± 0.148% at 192 h of incubation (∼11 half-lives). The cellular uptake of 188Re microspheres was 0.255-0.901 MBq. These values were concordant with Annexin FITC-V/PI apoptosis assay. At 192 h, 53.28% ± 0.01% of cells entered the apoptotic phase after treatment with 188Re microspheres, and only 39.34% ± 0.02% of cells remained viable. However, in the cells treated with 188ReO4- alone, 74.86% ± 0.005% of cells were viable, and only 24.75% ± 0.577% of cells were in the early apoptotic phase at 192 h. Conclusion: The data revealed that 188Re microspheres treatment led to significant growth inhibition in HepG2 cells compared with 188ReO4-.

QbD-driven development of phospholipid-embedded lipidic nanocarriers of raloxifene: extensive in vitro and in vivo evaluation studies.

Raloxifene (RLX) is popularly indicated in treatment of osteoporosis and prevention of breast cancer. Owing to its poor aqueous solubility, high pre-systemic metabolism, intestinal glucuronidation, and P-glycoprotein (P-gp) efflux, however, it demonstrates low (< 2%) and inconsistent oral bioavailability. The current work, Quality by Design (QbD)-driven development of phospholipid-embedded nanostructured lipidic carriers (NLCs) of RLX, accordingly, was undertaken to potentiate its lymphatic uptake, augment oral bioavailability, and possibly reduce drug dosage. Factor screening and failure mode effect analysis (FMEA) studies were performed to delineate high-risk factors using solid lipid (glyceryl monostearate), liquid lipid (vitamin E), and surfactant (Tween 80). Response surface optimization studies were performed employing the Box-Behnken design. Mathematical and graphical methods were adopted to embark upon the selection of optimized NLCs with various critical quality attributes (CQAs) of mean particle size as 186 nm, zeta potential of - 23.6 mV, entrapment efficiency of 80.09%, and cumulative drug release at 12 h of 83.87%. The DSC and FTIR studies, conducted on optimized NLCs, indicated successful entrapment of drug into the lipid matrix. In vitro drug release studies demonstrated Fickian diffusion mechanism. In vivo pharmacokinetic studies in rats construed significant improvement in AUC0-72 h (4.48-folds) and in Cmax (5.11-folds), unequivocally indicating markedly superior (p < 0.001) oral bioavailability of RLX-NLCs vis-à-vis marketed tablet formulation. Subsequently, level "A" in vitro/in vivo correlation (IVIVC) was also successfully attempted between the percentages of in vitro drug dissolved and of in vivo drug absorbed at the matching time points. In vitro cytotoxicity and cellular uptake studies also corroborated higher efficacy and successful localization of coumarin-6-loaded NLCs into MG-63 cells through microfluidic channels.

Clinical, immunological and molecular profiles of DOCK8 deficiency in six patients from a tertiary care centre in North India.

BACKGROUND: Dedicator of cytokinesis protein 8 (DOCK8) deficiency is an autosomal recessive form of combined immunodeficiency. This rare disorder is characterized by an increased predisposition to allergy, autoimmunity and malignancies. OBJECTIVES: To analyse clinical, immunological and molecular profiles of patients with DOCK8 deficiency. METHODS: Clinic records of all patients attending the primary immunodeficiency clinic from 2018 to 2021 were reviewed. Six patients from five families were found to have DOCK8 deficiency. RESULTS: Median age at diagnosis was 7.5 years (range 2-13), with a male/female ratio of 5 : 1. Among the six patients, recurrent eczematous skin lesions were the predominant cutaneous manifestation, present in five patients (83%). Warts and molluscum contagiosum were evident in two patients (33%) and one patient (16%), respectively. Two patients had recalcitrant prurigo nodularis lesions and two had epidermodysplasia verruciformis-like lesions. Food allergies and asthma were reported by one patient each. Of the six patients, recurrent sinopulmonary infections were detected in five (83%). Epstein-Barr virus-driven non-Hodgkin lymphoma with liver metastases was the only case of malignancy, in a 4-year-old boy. IgE was elevated in all patients. Lymphopenia and eosinophilia were observed in three patients (50%) and five patients (83.3%), respectively. Genetic analysis showed DOCK8 pathogenic variants in all patients: homozygous deletion mutations in two patients, compound heterozygous deletion mutations in one, and homozygous nonsense mutations in two. A novel pathogenic homozygous missense variant in the DOCK8 gene was identified in one patient. CONCLUSIONS: DOCK8 deficiency should be considered as a possibility in any patient with early onset eczema, cutaneous viral infections and increased predisposition to allergy, autoimmunity and malignancy.

Postbiotics Implication in the Microbiota-Host Intestinal Epithelial Cells Mutualism.

To sustain host health and provide the microbial community with a nutrient-rich environment, the host and gut microbiota must interact with one another. These interactions between commensal bacterial and intestinal epithelial cells (IECs) serve as the first line of defense against gut microbiota in preserving intestinal homeostasis. In this microenvironment, the post-biotics and similar molecules such as p40 exert several beneficial effects through regulation of IECs. Importantly, post-biotics were discovered to be transactivators of the EGF receptor (EGFR) in IECs, inducing protective cellular responses and alleviating colitis. The transient exposure to post-biotics such as p40 during the neonatal period reprograms IECs by upregulation of a methyltransferase, Setd1ß, leading to a sustained increase in TGF- ß release for the expansion of regulatory T cells (Tregs) in the intestinal lamina propria and durable protection against colitis in adulthood. This crosstalk between the IECs and post-biotic secreted factors was not reviewed previously. Therefore, this review describes the role of probiotic-derived factors in the sustainability of intestinal health and improving gut homeostasis via certain signaling pathways. In the era of precision medicine and targeted therapies, more basic, preclinical, and clinical evidence is needed to clarify the efficacy of probiotics released as functional factors in maintaining intestinal health and preventing and treating disease.

Exploring the therapeutic potential of sodium deoxycholate tailored deformable-emulsomes of etodolac for effective management of arthritis.

The current piece of research intends to evaluate the potential of combining etodolac with deformable-emulsomes, a flexible vesicular system, as a promising strategy for the topical therapy of arthritis. The developed carrier system featured nanometric dimensions (102 nm), an improved zeta potential (- 5.05 mV), sustained drug release (31.33%), and enhanced drug deposition (33.13%) of DE-gel vis-à-vis conventional system (10.34% and 14.71%). The amount of permeation of the developed nano formulation across skin layers was demonstrated through CLSM and dermatokinetics studies. The safety profile of deformable-emulsomes has been investigated through in vitro HaCaT cell culture studies and skin compliance studies. The efficacy of the DE-gel formulation was sevenfold higher in case of Xylene induced ear edema model and 2.2-folds in CFA induced arthritis model than that of group treated with conventional gel (p < 0.01). The main technological rationale lies in the use of phospholipid and sodium deoxycholate-based nanoscale flexible lipoidal vesicles, which effectively encapsulate drug molecules within their interiors. This encapsulation enhances the molecular interactions and facilitates the transportation of the drug molecule effectively to the target-site. Hence, these findings offer robust scientific evidence to support additional investigation into the potential utility of flexible vesicular systems as a promising drug delivery alternative for molecules of this nature.

Techno-functional attributes of oilseed proteins: influence of extraction and modification techniques.

Plant-based protein isolates and concentrates are nowadays becoming popular due to their nutritional, functional as well as religious concerns. Among plant proteins, oilseeds, a vital source of valuable proteins, are continuously being explored for producing protein isolates/concentrates. This article delineates the overview of conventional as well as novel methods for the extraction of protein and their potential impact on its hydration, surface properties, and rheological characteristics. Moreover, proteins undergo several modifications using physical, chemical, and biological techniques to enhance their functionality by altering their microstructure and physical performance. The modified proteins hold a pronounced scope in novel food formulations. An overview of these protein modification approaches and their effects on the functional properties of proteins have also been presented in this review.

Integrated in-silico and in-vitro assessments of HDAC6 inhibitor efficacy in mitigating amyloid beta pathology in Alzheimer's disease.

Alzheimer's disease, marked by memory loss and cognitive decline, is associated with amyloid-beta (Aß) peptide accumulation in the brain. The enzyme neprilysin (NEP), crucial for Aß degradation, decreases with age and in sporadic Alzheimer's disease, leading to increased Aß build-up. This study hypothesized the targeting of enzyme HDAC6, believed to influence NEP activity. An in-silico study was conducted using an FDA-approved drug database, with the focus on their interaction with the HDAC6 structure. Among tested ligands, Panobinostat showed the most favourable interaction with HDAC6. In-vitro experiments on the SH-SY5Y neuronal cell line confirmed these findings, with Panobinostat inhibiting HDAC6, enhancing NEP levels, and reducing Aß load. The study suggests Panobinostat as a potential Alzheimer's therapeutic agent, mitigating Aß accumulation via NEP upregulation. Further research is required for comprehensive understanding and validation.Communicated by Ramaswamy H. Sarma.

Integrating Omics Technologies for a Comprehensive Understanding of the Microbiome and Its Impact on Cattle Production.

Ruminant production holds a pivotal position within the global animal production and agricultural sectors. As population growth escalates, posing environmental challenges, a heightened emphasis is directed toward refining ruminant production systems. Recent investigations underscore the connection between the composition and functionality of the rumen microbiome and economically advantageous traits in cattle. Consequently, the development of innovative strategies to enhance cattle feed efficiency, while curbing environmental and financial burdens, becomes imperative. The advent of omics technologies has yielded fresh insights into metabolic health fluctuations in dairy cattle, consequently enhancing nutritional management practices. The pivotal role of the rumen microbiome in augmenting feeding efficiency by transforming low-quality feedstuffs into energy substrates for the host is underscored. This microbial community assumes focal importance within gut microbiome studies, contributing indispensably to plant fiber digestion, as well as influencing production and health variability in ruminants. Instances of compromised animal welfare can substantially modulate the microbiological composition of the rumen, thereby influencing production rates. A comprehensive global approach that targets both cattle and their rumen microbiota is paramount for enhancing feed efficiency and optimizing rumen fermentation processes. This review article underscores the factors that contribute to the establishment or restoration of the rumen microbiome post perturbations and the intricacies of host-microbiome interactions. We accentuate the elements responsible for responsible host-microbiome interactions and practical applications in the domains of animal health and production. Moreover, meticulous scrutiny of the microbiome and its consequential effects on cattle production systems greatly contributes to forging more sustainable and resilient food production systems, thereby mitigating the adverse environmental impact.

Evaluation of toxicity profile of kratom (Mitragyna speciosa Korth) decoction in rats.

Mitragyna speciosa Korth also known as kratom, is an herbal drug preparation for its therapeutic properties and opioid-replacement therapy. Kratom is consumed in a brewed decoction form in Malaysia and to date, no studies have characterized its chemical and toxicity profile. Thus, this study aims to evaluate kratom decoction's safety and toxicity profile after 28 days of treatment. Mitragynine content was quantified in kratom decoction and used as a marker to determine the concentration. Male and female Sprague Dawley rats were orally treated with vehicle or kratom decoction (10, 50 or 150 mg/kg) and two satellite groups were treated with vehicle and kratom decoction (150 mg/kg). Blood and organs were collected for hematology, biochemical and histopathology analysis at the end of treatment. No mortality was found after 28 days of treatment and no significant changes in body weight and hematology profile, except for low platelet count. High amounts of uric acid, AST, ALT and alkaline phosphatase were found in the biochemical analysis. Histological investigation of the heart and lungs detected no alterations except for the kidney, liver and brain tissues. In conclusion, repeated administration of kratom decoction provided some evidence of toxicity in the kidney and liver with no occurrence of mortality.

Structural-Based Virtual Screening of FDA-Approved Drugs Repository for NSP16 Inhibitors, Essential for SARS-COV-2 Invasion Into Host Cells: Elucidation From MM/PBSA Calculation.

NSP16 is one of the structural proteins of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) necessary for its entrance to the host cells. It exhibits 2'O-methyl-transferase (2'O-MTase) activity of NSP16 using methyl group from S-adenosyl methionine (SAM) by methylating the 5-end of virally encoded mRNAs and shields viral RNA, and also controls its replication as well as infection. In the present study, we used in silico approaches of drug repurposing to target and inhibit the SAM binding site in NSP16 using Food and Drug Administration (FDA)-approved small molecules set from Drug Bank database. Among the 2 456 FDA-approved molecules, framycetin, paromomycin, and amikacin were found to be significant binders against the SAM binding cryptic pocket of NSP16 with docking score of -13.708, -14.997 and -15.841 kcal/mol, respectively. Classical molecular dynamics (MD) simulation and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA)-based binding free energy calculation depicted that all these three framycetin, paromomycin, and amikacin might be promising therapeutic leads towards SARS-CoV-2 infections via host immune escape inhibition pathway.

A Novel Inhibitor of DKK1/LRP6 Interactions Against the Alzheimer Disease: An Insilco Approach.

The activation of the Wnt signaling pathway is implicated in a neuroprotective mechanism against the Alzheimer disease. When this pathway is blocked, it activates GSK3 beta, leading to tau hyperphosphorylation and the apoptosis of neurons. Dickkopf-related protein 1 (DKK1) is a protein that competes with the Wnt ligand for the low-density lipoprotein receptor-related protein 6 (LRP6) receptor's binding, interrupting the Wnt-induced Fzd-Wnt-LRP6 complex. This counteracts Wnt's neuroprotective effect and contributes to the progression of the Alzheimer disease. The aim of this study was to use in silico approach to develop new agents that can combat the Alzheimer disease by targeting the interaction between DKK1 and LRP6. To achieve this, we conducted a virtual screening (Vsw) of the Asinex-CNS database library (n = 54 513) compounds against a generated grid in LRP6 protein. From this screening, we selected 6 compounds based on their docking score and performed molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations on the selected ligands. Next, we evaluated the Absorption, Distribution, Metabolism, and Excretion (ADME) results of the 6 screened compounds using the Quick prop module of Schrödinger. We then employed several computational techniques, including PCA (Principal Component Analysis), DCCM (Dynamic Cross-Correlation Map), molecular dynamics simulation, and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA)-based negative binding free energy (BFE) calculation, to further analyze the compounds. Our extensive computational analysis resulted in the identification of 3 potential hits, LAS 29757582, LAS 29984441, and LAS 29757942. These compounds were found to block the interaction of DKK1 with LRP6 (A and B interface) protein, and their potential as therapeutic agents was supported by negative BFE calculation. Therefore, these compounds show potential as possible therapeutic agents for treating the Alzheimer disease through targeting the interaction between DKK1 and LRP6.

Short- and long-term safety and efficacy of corneal collagen cross-linking in progressive keratoconus: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The purpose of the study is to evaluate the safety and outcomes of corneal collagen cross-linking (CXL) and different CXL protocols in progressive keratoconus (PK) population at short and long-term. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted. A total of eight literature databases were searched (up to February 15, 2022). Randomized controlled trials (RCTs) comparing CXL versus placebo/control or comparing different CXL protocols in the PK population were included. The primary objective was assessment of outcomes of CXL versus placebo and comparison of different CXL protocols in terms of maximum keratometry (Kmax) or Kmax change from baseline (Δ), spherical equivalent, best corrected visual acuity (BCVA), and central corneal thickness (CCT) in both at short term (6 months) and long term (1st, 2nd, and 3rd year or more). The secondary objective was comparative evaluation of safety. For the meta-analysis, the RevMan5.3 software was used. RESULTS: A total of 48 RCTs were included. Compared to control, CXL was associated with improvement in Δ Kmax at 1 year (4 RCTs, mean difference [MD], -1.78 [-2.71, -0.86], P = 0.0002) and 2 and 3 years (1 RCT); ΔBCVA at 1 year (7 RCTs, -0.10 [-0.14, -0.06], P < 0.00001); and Δ CCT at 1 year (2 RCTs) and 3 years (1 RCT). Compared to conventional CXL (C-CXL), deterioration in Δ Kmax, ΔBCVA and endothelial cell density was seen at long term in the transepithelial CXL (TE-CXL, chemical enhancer). Up to 2 years, there was no difference between TE-CXL using iontophoresis (T-ionto) and C-CXL. At 2 and 4 years, C-CXL performed better compared to accelerated CXL (A-CXL) in terms of improving Kmax. Although CCT was higher in the A-CXL arm at 2 years, there was no difference at 4 years. While exploring heterogeneity among studies, selection of control eye (fellow eye of the same patient vs. eye of different patient) and baseline difference in Kmax were important sources of heterogeneity. CONCLUSION: CXL outperforms placebo/control in terms of enhancing Kmax and CCT, as well as slowing disease progression over time (till 3 years). T-ionto protocol, on the other hand, performed similarly to C-CXL protocol up to 2 years.