Corneal stress-strain index in myopic Indian population.

AIM: The purpose is to study the corneal stress-strain index (SSI) in myopic refractive error among Indian subjects. METHODS: A retrospective study where young myopic subjects aged between 11 and 35 years who had undergone corneal biomechanics assessment using Corvis ST between January 2017 and December 2021 were enrolled. Subjects with central corneal thickness (CCT) <500 µ, intraocular pressure (IOP) >21 mmHg, history of any systemic and ocular disease or any previous ocular surgery, high astigmatism, corneal disease such as keratoconus were excluded. Subjects with missing data or having poor quality scan were excluded. Corneal biomechanical properties and corneal SSI were assessed using Corvis ST. For statistical purposes, eyes were divided into four different groups and were analyzed using one-way ANOVA. RESULTS: Nine hundred and sixty-six myopic eyes with mean ± standard deviation age, IOP, and CCT of 26.89 ± 4.92 years, 16.94 ± 2.00 mmHg, and 540.18 ± 25.23 microns, respectively, were included. There were 311, 388, 172, and 95 eyes that were low, moderate, severe, and extreme myopic. Deformation amplitude ratio at 1 mm and 2 mm were similar across different myopic groups. A significant increase in max inverse radius, ambrosia relational thickness, biomechanically corrected IOP, integrated radius was noted with an increase in myopic refractive error. Corvis biomechanical index, corneal SSI was found to be decreased significantly with an increase in myopic refractive error. We noted a significant positive association between myopic refractive error and SSI (P < 0.001). CONCLUSION: Corneal SSI was found to be reduced in extreme myopic eyes.

Exploration of Antileishmanial Compounds Derived from Natural Sources.

Leishmaniasis is a deadly tropical disease that is neglected in many countries. World Health Organization, along with a few other countries, has been working together to protect against these parasites. Many novel drugs from the past few years have been discovered and subjected against leishmaniasis, which have been effective but they are quite expensive for lower-class people. Some drugs showed no effect on the patients, and the longer use of these medicines has made resistance against these deadly parasites. Researchers have been working for better medication by using natural products from medicinal plants (oils, secondary metabo-lites, plant extracts) and other alternatives to find active compounds as an alternative to the current synthetic drugs. MATERIALS AND METHODS: To find more potential natural products to treat Leishmania spp, a study has been conducted and reported many plant metabolites and other natural alternatives from plants and their extracts. Selected research papers with few term words such as natural products, plant metabolites, Leishmaniasis, in vivo, in vitro, and treatment against leishmania-sis; in the Google Scholar, PubMed, and Science Direct databases with selected research papers published between 2015 and 2021 have been chosen for further analysis has been included in this report which has examined either in vivo or in vitro analysis. RESULTS: This paper reported more than 20 novel natural compounds in 20 research papers that have been identified which report a leishmanicidal activity and shows an action against pro-mastigote, axenic, and intracellular amastigote forms. CONCLUSION: Medicinal plants, along with a few plant parts and extracts, have been reported as a possible novel anti-leishmanial medication. These medicinal plants are considered nontoxic to Host cells. Leishmaniasis treatments will draw on the isolated compounds as a source further and these compounds compete with those already offered in clinics.

Therapeutic management of osteodystrophia fibrosa in early weaned Malabari male goat kids.

Osteodystrophia fibrosa is a metabolic disease of goats resulting from the insufficient mineralization of bones, excessive bone resorption, and improper bone development, leading to subsequent accumulation of the fibrous connective tissue. This report describes the successful therapeutic management of acute osteodystrophia fibrosa in early-weaned goat kids by following a medical protocol. Three Malabari male goat kids of forty days old from two different litters of the same farm were presented with spontaneous, bilaterally symmetrical, non-inflammatory facial swelling, protruded tongue, prominent eyeballs, frothy drooling saliva, diarrhoea, and inanition due to the inability in mastication or suckling for the last two weeks. As per the history, these kids were weaned and started feeding pelleted concentrate feed and jackfruit leaves along with the milk sucking three weeks back only. On clinical examination, the vital parameters were normal and the key phenotypic abnormalities noted were the abnormally developed maxilla/mandible, manifested as a swelling that was hard to touch, and the loosely attached teeth. In biochemical evaluation, the reduction in Ca:P ratio was evident and the serum creatinine level was within normal ranges. A therapeutic protocol was devised for three weeks by including calcium (calcium gluconate), phosphate-binder (Kaolin), vitamins (Vit. ADEH), and anabolic steroid (Nandrolone; a well-established drug promoting formation and mineralization of bone in mammals). Considerable improvement was observed after three weeks of therapy and the animals were having apparently normal facial appearance on the review after three months. The kids showed normal healthy growth and were slaughtered later for meat purpose after gaining adult body weight. This report accentuates the possibility of acute hypocalcemia-induced osteodystrophia fibrosa, rather than hyperphosphatemia-induced, and its management using anabolic steroids for better clinical recovery in growing goat kids.

Visual outcomes and higher-order aberrations in eyes implanted with hybrid extended depth of focus intraocular lens.

PURPOSE: To study the visual outcomes and higher order aberrations in eyes implanted with Hybrid EDOF IOL, particularly in Indian eyes. MATERIALS AND METHODS: This is retrospective case series where subjects aged between 40-65 years and were implanted with LUCIDIS IOL by single surgeon were included. Subjects with Pre surgery corneal astigmatism > 1.50 D, corneal guttae, IOP >22mmHg, any ocular Co morbidities, Intra or post operative complication were excluded. At 1 month follow up, uncorrected visual acuities at distance (UCDVA), intermediate (UCIVA) and near (UCNVA), refraction were recorded. Internal Higher order aberrations and strehl ratio for a fixed pupil of 4mm and 6mm were calculated using NIDEK OPD Scan. Monocular defocus curve was obtained at 4 meter logMAR chart. RESULTS: Total of 55 eyes of 35 patients with mean±SD age of 58.50±7.49 years were evaluated. 89.09% of the eyes achieved visual acuity of 6/6. 49.09% could read N10 font at intermediate distance without any correction and 85.45% of the eyes had uncorrected near visual acuity of N6. Around 67% of the eyes did not require any refractive correction whereas around 26% of the eyes required correction upto ±0.25D. The defocus curve showed that visual acuity also ranges from 0.05 logMAR to 0.2 logMAR for Plano to -3.00D respectively. Mean±SD Strehl ratio at 4 and 6 mm pupil size was 0.06±0.04 and 0.02±0.02 respectively. CONCLUSION: Hybrid EDOF IOL such as LUCIDIS provides excellent vision at all distances. This could be attributed to IOL design which is spherical aberration neutral lens.

Pore-Confined π-Chromophoric Tetracene as a Visible Light Harvester toward MOF-Based Photocatalytic CO2 Reduction in Water.

Integrating photoactive π-chromophoric guest molecules inside the MOF nanopore can result in the emergence of light-responsive features, which in turn can be utilized for developing photoactive materials with inherent properties of MOF. Herein, we report the confining of π-chromophoric tetracene (TET) molecules inside the nanospace of postmodified Zr-MOF-808 (Zr-MOF) with MBA molecules (MBA = 2-(5'-methyl-[2,2'-bipyridine]-5-yl)acetic acid) for effectively utilizing its light-harvesting properties toward photocatalytic CO2 reduction. The confinement of the TET molecules as a photosensitizer and the covalent grafting of a catalytically active [Re(MBA)(CO)3Cl] complex, postsynthetically, result in a single integrated catalytic system named Zr-MBA-TET-Re-MOF. Photoreduction of CO2 over Zr-MBA-TET-Re-MOF showed the evolution of 805 µmol g-1 CO with 99.9% selectivity after 10 h of continuous visible light irradiation in water without any additional sacrificial electron donor and having the apparent quantum efficiency of 1.3%. In addition, the catalyst demonstrated an appreciable activity even under direct sunlight irradiation in aqueous medium with a maximum production of 362.7 µmol g-1 CO, thereby mimicking artificial photosynthesis. Moreover, electron transfer from TET to the catalytic center was supported by the formation of photoinduced TET radical cation, as inferred from in situ UV-vis spectra, electron paramagnetic resonance (EPR) analysis, and transient absorption (TA) studies. Additionally, the in situ diffuse reflectance infrared Fourier transform (DRIFT) measurements support that the photoreduction of CO2 to CO proceeds via *COOH intermediate formation. The close proximity of the light-harvesting molecule and catalytic center facilitated facile electron transfer from the photosensitizer to the catalyst during the CO2 reduction.

Comparative meta-analysis of antimicrobial resistance from different food sources along with one health approach in the Egypt and UK.

BACKGROUND: Antimicrobial resistance (AMR) is a critical global issue that poses significant threats to human health, animal welfare, and the environment. With the increasing emergence of resistant microorganisms, the effectiveness of current antimicrobial medicines against common infections is diminishing. This study aims to conduct a competitive meta-analysis of surveillance data on resistant microorganisms and their antimicrobial resistance patterns in two countries, Egypt and the United Kingdom (UK). METHODS: Data for this study were obtained from published reports spanning the period from 2013 to 2022. In Egypt and the UK, a total of 9,751 and 10,602 food samples were analyzed, respectively. Among these samples, 3,205 (32.87%) in Egypt and 4,447 (41.94%) in the UK were found to contain AMR bacteria. RESULTS: In Egypt, the predominant resistance was observed against ß-lactam and aminoglycosides, while in the United Kingdom, most isolates exhibited resistance to tetracycline and ß-lactam. The findings from the analysis underscore the increasing prevalence of AMR in certain microorganisms, raising concerns about the development of multidrug resistance. CONCLUSION: This meta-analysis sheds light on the escalating AMR problem associated with certain microorganisms that pose a higher risk of multidrug resistance development. The significance of implementing One Health AMR surveillance is emphasized to bridge knowledge gaps and facilitate accurate AMR risk assessments, ensuring consumer safety. Urgent actions are needed on a global scale to combat AMR and preserve the effectiveness of antimicrobial treatments for the well-being of all living beings.

Nanobiotics and the One Health Approach: Boosting the Fight against Antimicrobial Resistance at the Nanoscale.

Antimicrobial resistance (AMR) is a growing public health concern worldwide, and it poses a significant threat to human, animal, and environmental health. The overuse and misuse of antibiotics have contributed significantly and others factors including gene mutation, bacteria living in biofilms, and enzymatic degradation/hydrolyses help in the emergence and spread of AMR, which may lead to significant economic consequences such as reduced productivity and increased health care costs. Nanotechnology offers a promising platform for addressing this challenge. Nanoparticles have unique properties that make them highly effective in combating bacterial infections by inhibiting the growth and survival of multi-drug-resistant bacteria in three areas of health: human, animal, and environmental. To conduct an economic evaluation of surveillance in this context, it is crucial to obtain an understanding of the connections to be addressed by several nations by implementing national action policies based on the One Health strategy. This review provides an overview of the progress made thus far and presents potential future directions to optimize the impact of nanobiotics on AMR.

Role of corneal epithelial mapping, Corvis biomechanical index, and artificial intelligence-based tomographic biomechanical index in diagnosing spectrum of keratoconus.

AIM: The aim of the study was to evaluate the utility of epithelial mapping, Corvis biomechanical index (CBI), and tomographic biomechanical index (TBI) in diagnosing the spectrum of keratoconus (KC). METHODS: This was a retrospective study where KC subjects with an age between 11 and 50 years were enrolled. Subjects with ocular diseases, history of previous corneal surgery, corneal scars or hydrops, ocular trauma, ocular surface disorder, systemic disease, and poor-quality scans were excluded. KC was classified using Belin ABCD classification system. Epithelial thickness, corneal tomography, and corneal biomechanical measurements were recorded using Fourier-domain optical coherence tomography Avanti with corneal adaptor module, Pentacam HR, and Corvis® ST, respectively. To understand the utility of various corneal parameters in diagnosing spectrum of keratoconus, cutoff values for epithelial thickness at the thinnest location and its standard deviation (SD) were considered 45 and 3 microns, respectively, CBI of 0.5 and TBI of 0.29 was considered. RESULTS: Sixty-five eyes (45 - KC, 10 - subclinical KC (SBKC), and 10 - forme fruste [FF]) of 34 patients with a mean ± SD age of 30.73 ± 5.71 were included. In our keratoconic sample, epithelial mapping alone helped diagnose the 77.77% of cases, however, when combined with CBI, it helped diagnose 95.5% cases and when combined with TBI, it was useful in diagnosing 100% of cases. In SBKC group, 40% of cases were detected by epithelial mapping alone, and when combined with CBI, it helped diagnose 70% of cases and TBI further helped diagnose 90% of cases. We did not see any role of epithelial mapping in detecting FFKC cases whereas CBI and TBI helped diagnose 60% and 90% of cases, respectively. CONCLUSION: The utility of epithelial mapping as a solitary tool is limited in detecting the spectrum of KC, especially SB and FFKC. However, combining it with corneal biomechanical parameters could help improve the efficacy of diagnosis of KC.

Deciphering the Role of the Ser-Phosphorylation Pattern on the DNA-Binding Activity of Max Transcription Factor Using Chemical Protein Synthesis.

The chemical synthesis of site-specifically modified transcription factors (TFs) is a powerful method to investigate how post-translational modifications (PTMs) influence TF-DNA interactions and impact gene expression. Among these TFs, Max plays a pivotal role in controlling the expression of 15 % of the genome. The activity of Max is regulated by PTMs; Ser-phosphorylation at the N-terminus is considered one of the key regulatory mechanisms. In this study, we developed a practical synthetic strategy to prepare homogeneous full-length Max for the first time, to explore the impact of Max phosphorylation. We prepared a focused library of eight Max variants, with distinct modification patterns, including mono-phosphorylated, and doubly phosphorylated analogues at Ser2/Ser11 as well as fluorescently labeled variants through native chemical ligation. Through comprehensive DNA binding analyses, we discovered that the phosphorylation position plays a crucial role in the DNA-binding activity of Max. Furthermore, in vitro high-throughput analysis using DNA microarrays revealed that the N-terminus phosphorylation pattern does not interfere with the DNA sequence specificity of Max. Our work provides insights into the regulatory role of Max's phosphorylation on the DNA interactions and sequence specificity, shedding light on how PTMs influence TF function.

A Deep Learning Framework for the Characterization of Thyroid Nodules from Ultrasound Images Using Improved Inception Network and Multi-Level Transfer Learning.

In the past few years, deep learning has gained increasingly widespread attention and has been applied to diagnosing benign and malignant thyroid nodules. It is difficult to acquire sufficient medical images, resulting in insufficient data, which hinders the development of an efficient deep-learning model. In this paper, we developed a deep-learning-based characterization framework to differentiate malignant and benign nodules from the thyroid ultrasound images. This approach improves the recognition accuracy of the inception network by combining squeeze and excitation networks with the inception modules. We have also integrated the concept of multi-level transfer learning using breast ultrasound images as a bridge dataset. This transfer learning approach addresses the issues regarding domain differences between natural images and ultrasound images during transfer learning. This paper aimed to investigate how the entire framework could help radiologists improve diagnostic performance and avoid unnecessary fine-needle aspiration. The proposed approach based on multi-level transfer learning and improved inception blocks achieved higher precision (0.9057 for the benign class and 0.9667 for the malignant class), recall (0.9796 for the benign class and 0.8529 for malignant), and F1-score (0.9412 for benign class and 0.9062 for malignant class). It also obtained an AUC value of 0.9537, which is higher than that of the single-level transfer learning method. The experimental results show that this model can achieve satisfactory classification accuracy comparable to experienced radiologists. Using this model, we can save time and effort as well as deliver potential clinical application value.

Confining Molecular Photosensitizer and Catalyst in MOF toward Artificial Photosynthesis: Validating Electron Transfer by In Situ DRIFT Study.

Exploration of different chemical systems for photocatalytic CO2 reduction by using sunlight en route to the achievement of artificial photosynthesis stems from global warming and the energy crisis. In this work, we have covalently grafted the molecular photosensitizer (PS) [Ru(MBA)(bpy)2]Cl2 (bpy: 2,2'-bipyridine) and the catalyst [Mn(MBA)(CO)3Br] inside the Zr-MOF-808 (Zr-MOF) nanopore postmodified with 2-(5'-methyl-[2,2'-bipyridine]-5-yl)acetic acid (H-MBA) and developed a single integrated system named Zr-MBA-Ru/Mn-MOF for the CO2 reduction reaction (CO2RR). Zr-MBA-Ru/Mn-MOF is found to be active toward CO2-to-CO conversion, with a maximum production of 1027 µmol g-1 after 26 h of reaction having >99% selectivity in the aqueous medium without any additional hole scavenger. The catalyst with direct sunlight in the aqueous medium is equally active for CO production, thus mimicking the natural photosynthetic process. We have performed an in situ diffuse reflectance Fourier transform infrared spectroscopy (FTIR) (DRIFT) study to unveil the electron transfer from the PS to the catalytic center during CO2 reduction by monitoring the changes in the carbonyl stretching frequency in the [Mn(MBA)(CO)3Br] center and correlated with the density functional theory (DFT) calculations. Additionally, we have performed in situ DRIFT spectroscopy to understand the reaction mechanism for the CO2-to-CO conversion.

Enabling Peptide Ligation at Aromatic Junction Mimics via Native Chemical Ligation and Palladium-Mediated S-Arylation.

Synthetic strategies to assemble peptide fragments are in high demand to access homogeneous proteins for various applications. Here, we combined native chemical ligation (NCL) and Pd-mediated Cys arylation to enable practical peptide ligation at aromatic junctions. The utility of one-pot NCL and S-arylation at the Phe and Tyr junctions was demonstrated and employed for the rapid chemical synthesis of the DNA-binding domains of the transcription factors Myc and Max. Organometallic palladium reagents coupled with NCL enabled a practical strategy to assemble peptides at aromatic junctions.

Magnetic resonance imaging is safe in patients with left bundle branch pacing.

BACKGROUND: The use of left bundle branch pacing (LBBP) has dramatically increased since it was first described in 2016, but to date there are no published data on the safety of performing magnetic resonance imaging (MRI) in these patients. METHODS: Patients with LBBP who underwent MRI between January 2016 and October 2022 were retrospectively studied in our clinical center, which has a special program for imaging patients with cardiac devices. All patients underwent close cardiac monitoring throughout the MRI scans. Occurrence of arrhythmias or other adverse effects during MRI were assessed. LBBP lead parameters immediately pre- and post-MRI and at an outpatient follow-up were compared. RESULTS: Fifteen patients with LBBP underwent a total of 19 MRI sessions during the study period. Lead parameters did not significantly change after the MRI or on follow-up, which took place at a median of 91 days after the MRI. No patient developed arrhythmias during the MRI sessions, and no adverse effects such as lead dislodgement were reported. CONCLUSION: Although larger studies are necessary to verify our findings, MRI in patients with LBBP appears safe based on this initial case series.

Age-related variations in corneal stress-strain index in the Indian population.

Purpose: To report age-related variations in corneal stress-strain index (SSI) in healthy Indians. Methods: It was a retrospective study where healthy Indian individuals aged between 11 and 70 years who had undergone corneal biomechanics assessment using Corvis ST between January 2017 and December 2021 were enrolled. Composite corneal biomechanical parameters and corneal SSI were abstracted from Corvis ST and compared across different age groups using one-way analysis of variance (ANOVA). Also, Pearson's correlation was used to evaluate the association between age and SSI. Results: Nine hundred and thirty-six eyes of 936 patients with ages between 11 and 77 years with mean ± SD intraocular pressure (IOP) and pachymetry of 16.52 ± 2.10 mmHg and 541.13 ± 26.39 µs, respectively. Composite corneal biomechanical parameters such as deformation amplitude ratio max at 1 mm (P < 0.001) and 2 mm (P < 0.001), biomechanically corrected IOP (P = 0.004), stiffness parameter at A1 (P < 0.001, Corvis biomechanical index (P < 0.018), and SSI (P < 0.001) were found to be significantly different as a function of age group. We noted a statistically significant positive association of SSI with age (P < 0.001), spherical equivalent refractive error (P < 0.001), and IOP (P < 0.001) and a significant negative association with anterior corneal astigmatism (P < 0.001) and Anterior chamber depth (ACD) (P < 0.001). Also, SSI was positively associated with SPA1 and bIOP, whereas negatively associated with integrated radius, max inverse radius, and Max Deformation amplitude (DA) ratio at 1 mm and 2 mm. Conclusion: We noted a positive association of corneal SSI with age in normal healthy Indian eyes. This information could be helpful for future corneal biomechanical research.

Novel fluorobenzothiazole as a dual inhibitor of gyrase B and topoisomerase IV against Gram-positive pathogens.

Aim: The development of a novel inhibitor targeting gyrase B and topoisomerase IV offers an opportunity to combat multidrug resistance. Methods: We investigated the activity of RBx 10080758 against Gram-positive bacteria in vitro and in vivo. Results: RBx 10080758 showed a potent 50% inhibitory concentration of 0.13 µM and 0.25 µM against gyrase B and topoisomerase IV, respectively, and exhibited strong whole-cell in vitro activity with MIC ranges of 0.015-0.06 and 0.015-0.03 µg/ml against Staphylococcus aureus and Streptococcus pneumoniae, respectively. In a rat thigh infection model with methicillin-resistant S. aureus, RBx 10080758 at 45 mg/kg exhibited a >3 log10 CFU reduction in thigh muscles. Conclusion: RBx 10080758 displayed potent activity against multiple multidrug-resistant Gram-positive bacteria with a dual-targeting mechanism of action.

Therapeutic applications of nanobiotechnology.

Nanobiotechnology, as a novel and more specialized branch of science, has provided a number of nanostructures such as nanoparticles, by utilizing the methods, techniques, and protocols of other branches of science. Due to the unique features and physiobiological characteristics, these nanostructures or nanocarriers have provided vast methods and therapeutic techniques, against microbial infections and cancers and for tissue regeneration, tissue engineering, and immunotherapies, and for gene therapies, through drug delivery systems. However, reduced carrying capacity, abrupt and non-targeted delivery, and solubility of therapeutic agents, can affect the therapeutic applications of these biotechnological products. In this article, we explored and discussed the prominent nanobiotechnological methods and products such as nanocarriers, highlighted the features and challenges associated with these products, and attempted to conclude if available nanostructures offer any scope of improvement or enhancement. We aimed to identify and emphasize the nanobiotechnological methods and products, with greater prospect and capacity for therapeutic improvements and enhancements. We found that novel nanocarriers and nanostructures, such as nanocomposites, micelles, hydrogels, microneedles, and artificial cells, can address the associated challenges and inherited drawbacks, with help of conjugations, sustained and stimuli-responsive release, ligand binding, and targeted delivery. We recommend that nanobiotechnology, despite having few challenges and drawbacks, offers immense opportunities that can be harnessed in delivering quality therapeutics with precision and prediction. We also recommend that, by exploring the branched domains more rigorously, bottlenecks and obstacles can also be addressed and resolved in return.

SARS-CoV-2 neutralizing antibody epitopes are overlapping and highly mutated which raises the chances of escape variants and requires development of broadly reactive vaccines.

The rapid adaptation of SARS-CoV-2 within the host species and the increased viral transmission triggered the evolution of different SARS-CoV-2 variants. Though numerous monoclonal antibodies (mAbs) have been identified as prophylactic therapy for SARS-CoV-2, the ongoing surge in the number of SARS-CoV-2 infections shows the importance of understanding the mutations in the spike and developing novel vaccine strategies to target all variants. Here, we report the map of experimentally validated 74 SARS-CoV-2 neutralizing mAb binding epitopes of all variants. The majority (87.84%) of the potent neutralizing epitopes are localized to the receptor-binding domain (RBD) and overlap with each other, whereas limited (12.16%) epitopes are found in the N-terminal domain (NTD). Notably, 69 out of 74 mAb targets have at least one mutation at the epitope sites. The potent epitopes found in the RBD show higher mutations (4-10aa) compared to lower or modest neutralizing antibodies, suggesting that these epitopes might co-evolve with the immune pressure. The current study shows the importance of determining the critical mutations at the antibody recognition epitopes, leading to the development of broadly reactive immunogens targeting multiple SARS-CoV-2 variants. Further, vaccines inducing both humoral and cell-mediated immune responses might prevent the escape of SARS-CoV-2 variants from neutralizing antibodies.

Impact of Exercise on Fatigue in Patients Undergoing Dialysis in a Tertiary Care Hospital.

Background Chronic kidney disease (CKD) is a current public health problem associated with progression to end-stage renal disease (ESRD), cardiovascular disease, and increased mortality rates. The disease is progressive. It is estimated that there are about 20-25 patients with milder kidney damage for every patient on renal replacement therapy. Physical activity is one of the critical elements for the prevention of chronic diseases and exercises in CKD help to improve muscular strength, cardiorespiratory endurance, overall function, and quality of life. Fatigue can cause an inability to perform exercises and can affect physiological and psychological function. There is a need to analyze the effects of exercises on fatigue in outpatients undergoing dialysis in the Indian rural population. Methods This study was a randomized, controlled, interventional, single-center trial. The participants diagnosed with ESRD and who were on hemodialysis were randomly assigned to group A, the exercise group (EG), which had exercise training during dialysis, and group B, the control group (CG), which had no added exercises during dialysis or at home and followed a standard routine method. The outcome measure of fatigue was evaluated through the total Fatigue Assessment Scale (FAS) score at 0, 12, 24, and 36 weeks. The exercise was pilot tested and planned based on the guidelines and carried out during hemodialysis two days a week. It was followed up with a five-day home exercise program when the patients did not undergo dialysis. Results A total of 48 participants were chosen for the study, of which 30 participants completed 36 weeks of training, with exercise adherence of more than 60%. There was a statistically significant difference in FAS between the two groups (F (3, 84) = 10.513, P < 0.001) at a 95% confidence interval (P < 0.05). Post hoc comparisons between groups at baseline and at 12 weeks indicated that there was no significant difference in FAS (P = 0.271 and P = 0.08), but recorded a significant difference (P = 0.001) at 24 and 36 weeks, respectively, between the EG and CG. Conclusions The results indicate that the intradialytic exercise intervention was effective in reducing the level of fatigue in outpatients undergoing dialysis on a long-term exercise program.

Autophagy as a Therapeutic Target for Chronic Kidney Disease and the Roles of TGF-ß1 in Autophagy and Kidney Fibrosis.

Autophagy is a lysosomal protein degradation system that eliminates cytoplasmic components such as protein aggregates, damaged organelles, and even invading pathogens. Autophagy is an evolutionarily conserved homoeostatic strategy for cell survival in stressful conditions and has been linked to a variety of biological processes and disorders. It is vital for the homeostasis and survival of renal cells such as podocytes and tubular epithelial cells, as well as immune cells in the healthy kidney. Autophagy activation protects renal cells under stressed conditions, whereas autophagy deficiency increases the vulnerability of the kidney to injury, resulting in several aberrant processes that ultimately lead to renal failure. Renal fibrosis is a condition that, if chronic, will progress to end-stage kidney disease, which at this point is incurable. Chronic Kidney Disease (CKD) is linked to significant alterations in cell signaling such as the activation of the pleiotropic cytokine transforming growth factor-ß1 (TGF-ß1). While the expression of TGF-ß1 can promote fibrogenesis, it can also activate autophagy, which suppresses renal tubulointerstitial fibrosis. Autophagy has a complex variety of impacts depending on the context, cell types, and pathological circumstances, and can be profibrotic or antifibrotic. Induction of autophagy in tubular cells, particularly in the proximal tubular epithelial cells (PTECs) protects cells against stresses such as proteinuria-induced apoptosis and ischemia-induced acute kidney injury (AKI), whereas the loss of autophagy in renal cells scores a significant increase in sensitivity to several renal diseases. In this review, we discuss new findings that emphasize the various functions of TGF-ß1 in producing not just renal fibrosis but also the beneficial TGF-ß1 signaling mechanisms in autophagy.