Assessment of Liver Transplant Eligibility in Chronic Liver Disease Patients: A Cross-Sectional Study From a Tertiary Care Hospital of Pakistan.

INTRODUCTION: The burden of chronic liver disease (CLD) is increasing globally and the ultimate treatment is a liver transplant. As Pakistan is a developing country, liver transplantation is not easily available due to limited resources. This study aims to assess the patients with CLD for liver transplantation and to find the frequency of eligible candidates for liver transplantation. METHODS: A cross-sectional observational study was conducted on patients with CLD from June 2022 to December 2022. Total bilirubin, serum creatinine complete blood count, serum electrolytes, and international normalised ratio (INR) were done. The Model for End-Stage Liver Disease (MELD) score was calculated and the frequency of eligible patients for liver transplant was determined. Data was entered and analyzed using Statistical Package for Social Sciences (SPSS) version 22 (IBM Corp., Armonk, NY, USA). RESULTS: In our study, 149 patients were enrolled with a mean age of 46.81±15.7 years. There were 58.7% male and 41.6% female patients. The mean duration of liver cirrhosis was 18.22±11.7 months. The mean MELD score was 20.71±5.2. The common liver cirrhosis stages were stage II and stage II was found in 32.2% of each. Hepatocellular carcinoma (HCC) was present in 15.4% of patients. There were 25.5% of patients eligible for liver transplants. CONCLUSION: In our study, we found that significant numbers of patients with CLD were eligible for liver transplantation.

A grid-forming approach utilizing DC bus dynamics for low inertia power systems with HVDC applications.

While power electronic converters, such as voltage source converters (VSCs), are crucial for the operation of converter-dominated renewables and their integration with the electricity grid, their reliance on VSCs can pose a challenge. The limited inertia of these sources can lead to a deterioration of the rate of change of frequency, potentially causing power system stability issues. A grid-forming approach utilizing dc-link dynamics is one of the attractive alternatives to achieve grid synchronization and support grid frequency. Existing grid-forming control schemes, which assume a constant or virtually constant dc source, rely on a fixed physical dc-link capacitor. Nonetheless, the inertia support from such a capacitor is brief, owing to its limited energy storage capability. Consequently, enhancing inertia becomes imperative; otherwise, it may result in an increased rate of change of voltage on the dc side, potentially leading to issues with protection, undesirable interactions, and system instability. This paper proposes a new grid-forming control strategy that considers a virtual capacitor to achieve grid synchronization while simultaneously providing the network with inertia response services during power imbalances. Moreover, including a virtual resistor in the controller effectively attenuates power and dc voltage oscillations. Simulations using Simulink and small signal stability analysis are conducted to validate the efficacy of the proposed controller.

A Systematic Bioinformatics Approach for Mapping the Minimal Set of a Viral Peptidome.

Sequence changes in viral genomes generate protein sequence diversity that enables viruses to evade the host immune system, hindering the development of effective preventive and therapeutic interventions. The massive proliferation of sequence data provides unprecedented opportunities to study viral adaptation and evolution. An alignment-free approach removes various restrictions posed by an alignment-dependent approach for studying sequence diversity. The publicly available tool, UNIQmin, offers an alignment-free approach for studying viral sequence diversity at any given rank of taxonomy lineage and is big data ready. The tool performs an exhaustive search to determine the minimal set of sequences required to capture the peptidome diversity within a given dataset. This compression is possible through the removal of identical sequences and unique sequences that do not contribute effectively to the peptidome diversity pool. Herein, we describe a detailed four-part protocol utilizing UNIQmin to generate the minimal set for the purpose of viral diversity analyses, alignment-free at any rank of the taxonomy lineage, using the recent global public health threat Monkeypox virus (MPX) sequence data as a case study. The protocol enables a systematic bioinformatics approach to study sequence diversity across taxonomic lineages, which is crucial for our future preparedness against viral epidemics. This is particularly important when data are abundant, freely available, and alignment is not an option. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Tool installation and input file preparation Basic Protocol 2: Generation of a minimal set of sequences for a given dataset Basic Protocol 3: Comparative minimal set analysis across taxonomic lineage ranks Basic Protocol 4: Factors affecting the minimal set of sequences.

Complete mitochondrial genomes of edible mushrooms: features, evolution, and phylogeny.

Edible mushrooms are an important food source with high nutritional and medicinal value. They are a useful source for studying phylogenetic evolution and species divergence. The exploration of the evolutionary relationships among these species conventionally involves analyzing sequence variations within their complete mitochondrial genomes, which range from 31,854 bp (Cordyceps militaris) to 197,486 bp (Grifolia frondosa). The study of the complete mitochondrial genomes of edible mushrooms has emerged as a critical field of research, providing important insights into fungal genetic makeup, evolution, and phylogenetic relationships. This review explores the mitochondrial genome structures of various edible mushroom species, highlighting their unique features and evolutionary adaptations. By analyzing these genomes, robust phylogenetic frameworks are constructed to elucidate mushrooms lineage relationships. Furthermore, the exploration of different variations of mitochondrial DNA presents novel opportunities for enhancing mushroom cultivation biotechnology and medicinal applications. The mitochondrial genomic features are essential for improving agricultural practices and ensuring food security through improved crop productivity, disease resistance, and nutritional qualities. The current knowledge about the mitochondrial genomes of edible mushrooms is summarized in this review, emphasising their significance in both scientific research and practical applications in bioinformatics and medicine.

A global initiative on addressing bioinformatics' grand challenges.

The Bioinformatics Grand Challenges Consortium (BGCC) is a collaborative effort to address the most pressing challenges in bioinformatics. Initially focusing on education and training, the consortium successfully defined seven key grand challenges and is actively developing actionable solutions for these challenges. Building on this foundation, the BGCC plans to broaden its focus to include additional grand challenges in emerging areas.

Digital health technologies in enhancing patient and caregiver engagement in heart failure management: Opportunities and challenges.

The management of heart failure has undergone significant evolution, advancing from the initial utilization of digitalis and diuretics to the contemporary practice of personalized medicine and sophisticated device therapy. Despite these advancements, the persistent challenge of high hospitalization and readmission rates underscores an urgent need for innovative solutions. This manuscript explores how the integration of digital health technologies into interventional cardiology marks a paradigm shift in the management of heart failure. These technologies are no longer mere adjuncts but have become foundational to a modern approach, providing tools for continuous monitoring, patient education, and improved outcomes post-intervention. Through an examination of current trends, this perspective article highlights the transformative impact of wearable technologies, telehealth platforms, and advanced analytical tools in reshaping patient engagement and enabling proactive care strategies. Case studies illustrate the practical advantages, including enhanced medication adherence, early detection of heart failure signs, and a reduction in healthcare facility burdens. Central to this new digital health landscape is the Information Technology Management (ITM) system, a framework poised to revolutionize patient and caregiver engagement and pave the way for the future of interventional cardiology. This manuscript delineates the ITM system's innovative architecture and its consequential role in refining current and prospective cardiological interventions.

Nonequivalent Atomic Vibrations at Interfaces in a Polar Superlattice.

In heterostructures made from polar materials, e.g., AlN-GaN-AlN, the nonequivalence of the two interfaces is long recognized as a critical aspect of their electronic properties; in that, they host different 2D carrier gases. Interfaces play an important role in the vibrational properties of materials, where interface states enhance thermal conductivity and can generate unique infrared-optical activity. The nonequivalence of the corresponding interface atomic vibrations, however, is not investigated so far due to a lack of experimental techniques with both high spatial and high spectral resolution. Herein, the nonequivalence of AlN-(Al0.65Ga0.35)N and (Al0.65Ga0.35)N-AlN interface vibrations is experimentally demonstrated using monochromated electron energy-loss spectroscopy in the scanning transmission electron microscope (STEM-EELS) and density-functional-theory (DFT) calculations are employed to gain insights in the physical origins of observations. It is demonstrated that STEM-EELS possesses sensitivity to the displacement vector of the vibrational modes as well as the frequency, which is as critical to understanding vibrations as polarization in optical spectroscopies. The combination enables direct mapping of the nonequivalent interface phonons between materials with different phonon polarizations. The results demonstrate the capacity to carefully assess the vibrational properties of complex heterostructures where interface states dominate the functional properties.

Neuroretinal degeneration in a mouse model of systemic chronic immune activation observed by proteomics.

Blindness or vision loss due to neuroretinal and photoreceptor degeneration affects millions of individuals worldwide. In numerous neurodegenerative diseases, including age-related macular degeneration, dysregulated immune response-mediated retinal degeneration has been found to play a critical role in the disease pathogenesis. To better understand the pathogenic mechanisms underlying the retinal degeneration, we used a mouse model of systemic immune activation where we infected mice with lymphocytic choriomeningitis virus (LCMV) clone 13. Here, we evaluated the effects of LCMV infection and present a comprehensive discovery-based proteomic investigation using tandem mass tag (TMT) labeling and high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS). Changes in protein regulation in the posterior part of the eye, neuroretina, and RPE/choroid were compared to those in the spleen as a secondary lymphoid organ and to the kidney as a non-lymphoid but encapsulated organ at 1, 8, and 28 weeks of infection. Using bioinformatic tools, we found several proteins responsible for maintaining normal tissue homeostasis to be differentially regulated in the neuroretina and the RPE/choroid during the degenerative process. Additionally, in the organs we observed, several important protein pathways contributing to cellular homeostasis and tissue development were perturbed and associated with LCMV-mediated inflammation, promoting disease progression. Our findings suggest that the response to a systemic chronic infection differs between the neuroretina and the RPE/choroid, and the processes induced by chronic systemic infection in the RPE/choroid are not unlike those induced in non-immune-privileged organs such as the kidney and spleen. Overall, our data provide detailed insight into several molecular mechanisms of neuroretinal degeneration and highlight various novel protein pathways that further suggest that the posterior part of the eye is not an isolated immunological entity despite the existence of neuroretinal immune privilege.

Lipase and Protease Production Ability of Multi-drug Resistant Bacteria Worsens the Outcomes of Wound Infections.

BACKGROUND: Surgical site infections are one of the major clinical problems in surgical departments that cost hundreds of millions of dollars to healthcare systems around the world. AIM: The study aimed to address the pressing issue of surgical site infections, which pose significant clinical and financial burdens on healthcare systems globally. Recognizing the substantial costs incurred due to these infections, the research has focused on understanding the role of lipase and protease production by multi-drug resistant bacteria isolated from surgical wounds in the development of post-surgical wound infections. METHODS: For these purposes, 153 pus specimens were collected from patients with severe post-surgical wound infections having prolonged hospital stays. The specimens were inoculated on appropriate culture media. Gram staining and biochemical tests were used for the identification of bacterial growth on suitable culture media after 24 hours of incubation. The isolated pathogens were then applied for lipase and protease, key enzymes that could contribute to wound development, on tributyrin and skimmed milk agar, respectively. Following the CSLI guidelines, the Kirby-Bauer disc diffusion method was used to assess antibiotic susceptibility patterns. The results revealed that a significant proportion of the samples (127 out of 153) showed bacterial growth of Gram-negative (n = 66) and Gram-positive (n = 61) bacteria. In total, isolated 37 subjects were declared MDR due to their resistance to three or more than three antimicrobial agents. The most prevalent bacteria were Staphylococcus aureus (29.13%), followed by S. epidermidis (18.89%), Klebsiella pneumoniae (18.89%), Escherichia coli (14.96%), Pseudomonas aeruginosa (10.23%), and Proteus mirabilis (7.87%). Moreover, a considerable number of these bacteria exhibited lipase and protease activity with 70 bacterial strains as lipase positive on tributyrin agar, whereas 74 bacteria showed protease activity on skimmed milk agar with P. aeruginosa as the highest lipase (69.23%) and protease (76.92%) producer, followed by S. aureus (lipase 62.16% and protease 70.27%). RESULTS: The antimicrobial resistance was evaluated among enzyme producers and non-producers and it was found that the lipase and protease-producing bacteria revealed higher resistance to selected antibiotics than non-producers. Notably, fosfomycin and carbapenem were identified as effective antibiotics against the isolated bacterial strains. However, gram-positive bacteria displayed high resistance to lincomycin and clindamycin, while gram-negative bacteria were more resistant to cefuroxime and gentamicin. CONCLUSION: In conclusion, the findings suggest that lipases and proteases produced by bacteria could contribute to drug resistance and act as virulence factors in the development of surgical site infections. Understanding the role of these enzymes may inform strategies for preventing and managing post-surgical wound infections more effectively.

Dupilumab Reduces Asthma Disease Burden and Recurrent SCS Use in Patients with CRSwNP and Coexisting Asthma.

Purpose: Dupilumab significantly reduced the requirement for systemic corticosteroids (SCS) in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). Patients with CRSwNP and coexisting asthma typically have a higher disease burden and have more difficulty in managing disease. Here, we report an analysis of asthma outcomes and SCS use in patients with CRSwNP and coexisting asthma. Patients and Methods: This was a post hoc analysis of the randomized, placebo-controlled SINUS-24 and SINUS-52 studies (NCT02912468/NCT02898454) in patients with severe CRSwNP and coexisting asthma (patient self-reported) from the pooled intention-to-treat population randomized to dupilumab 300 mg every 2 weeks or placebo. On-treatment SCS use was estimated using Kaplan-Meier analysis. Forced expiratory volume in 1 s (FEV1), percent predicted FEV1, and the 6-item Asthma Control Questionnaire (ACQ-6) were assessed at baseline and Week 24 (pooled SINUS-24/52) in patients with/without history of asthma exacerbation or prior SCS use. Results: Of 337 patients with coexisting asthma, 88 (26%) required on-treatment SCS use. The requirement for on-treatment SCS use for any reason was significantly lower with dupilumab (20/167 patients; 12%) vs placebo (68/170; 40%); hazard ratio (95% confidence interval) 0.248 (0.150-0.409); p < 0.0001. The most frequent reasons for SCS use were nasal polyps (dupilumab 3% and placebo 27%) and asthma (2% and 9%, respectively). FEV1, percent predicted FEV1, and ACQ-6 were all significantly improved at Week 24 with dupilumab vs placebo irrespective of history of asthma exacerbation or prior SCS use (all p < 0.01). Conclusion: Dupilumab significantly reduced the requirement for SCS and improved asthma outcomes irrespective of history of asthma exacerbation or prior SCS use vs placebo in patients with CRSwNP and coexisting asthma, demonstrating concomitant reduction of SCS use and asthma disease burden in these patients.

Prevalence of type 2 inflammatory signatures and efficacy of dupilumab in patients with chronic rhinosinusitis with nasal polyps from two phase 3 clinical trials: SINUS-24 and SINUS-52.

BACKGROUND: This post hoc analysis of the international SINUS-24/-52 trials (NCT02912468/NCT02898454) aimed to assess dupilumab efficacy in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) according to different definitions of type 2 inflammatory signature. METHODS: Six definitions of type 2 inflammation were used: ≥150 eosinophils/µL or total immunoglobulin E (IgE) ≥100 IU/mL with a coexisting type 2 condition; ≥150 eosinophils/µL or total IgE ≥100 IU/mL; ≥150 eosinophils/µL; ≥250 eosinophils/µL or total IgE ≥100 IU/mL; coexisting asthma or ≥300 eosinophils/µL; presence of a coexisting type 2 condition. Odds ratios (ORs; dupilumab vs. placebo) for achieving clinically meaningful improvement (≥1 point) from baseline to week 24 (pooled SINUS-24/-52) and week 52 (SINUS-52) were calculated for nasal polyp score (NPS; range 0-8), nasal congestion/obstruction score (NC; 0-3), and loss of smell score (LoS; 0-3). RESULTS: At baseline (n = 724), most patients displayed a type 2 inflammatory signature across definitions (64.2%-95.3%). At week 24, ORs for clinically meaningful improvement ranged from 11.9 to 14.9 for NPS across type 2 definitions, 6.5-9.6 for NC, and 12.2-17.8 for LoS (all p < 0.0001). OR ranges were similar or greater at week 52: 19.0-36.6, 7.6-12.1, and 9.2-33.5, respectively (all p < 0.0001). CONCLUSION: Most patients with CRSwNP in the SINUS study had type 2 inflammation. Dupilumab demonstrated robust efficacy across definitions of type 2 inflammation, consistent with its profile as an inhibitor of Interleukin-4 and Interleukin-13 signaling, key and central drivers of type 2 inflammation in CRSwNP. KEY POINTS: This study assessed type 2 inflammation prevalence and dupilumab efficacy in chronic rhinosinusitis with nasal polyps according to algorithm-defined type 2 inflammation Dupilumab efficacy was similar across all type 2 definitions.

The Role of the Gut Microbiome in Hematological Cancers.

Humans are in a complex symbiotic relationship with a wide range of microbial organisms, including bacteria, viruses, and fungi. The evolution and composition of the human microbiome can be an indicator of how it may affect human health and susceptibility to diseases. Microbiome alteration, termed as dysbiosis, has been linked to the pathogenesis and progression of hematological cancers. A variety of mechanisms, including epithelial barrier disruption, local chronic inflammation response trigger, antigen dis-sequestration, and molecular mimicry, have been proposed to be associated with gut microbiota. Dysbiosis may be induced or worsened by cancer therapies (such as chemotherapy and/or hematopoietic stem cell transplantation) or infection. The use of antibiotics during treatment may also promote dysbiosis, with possible long-term consequences. The aim of this review is to provide a succinct summary of the current knowledge describing the role of the microbiome in hematological cancers, as well as its influence on their therapies. Modulation of the gut microbiome, involving modifying the composition of the beneficial microorganisms in the management and treatment of hematological cancers is also discussed. Additionally discussed are the latest developments in modeling approaches and tools used for computational analyses, interpretation and better understanding of the gut microbiome data.

Impact of Dupilumab on Sinonasal Symptoms and Outcomes in Severe Chronic Rhinosinusitis With Nasal Polyps.

OBJECTIVES: To assess the severity of the top 5 22-item Sino-Nasal Outcome Test (SNOT-22) items ranked most important by patients with chronic rhinosinusitis with nasal polyps (CRSwNP), the effect of dupilumab on these items, and their association with objective disease measures. STUDY DESIGN: Post hoc analysis of the SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) clinical trials. SETTING: Multinational, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies. METHODS: Patients ranked the SNOT-22 items most affecting their health at baseline. Item symptom severity (0-5 scale) was assessed at baseline, Week 24 (W24), and Week 52 (W52). Changes in nasal polyps score (NPS) and Lund-Mackay (LMK) scores were assessed in patients with/without SNOT-22 items improvements of at least 1 severity group point at W24 and W52. RESULTS: The SNOT-22 items ranked most important at baseline were "decreased sense of smell/taste" (87% of patients), followed by "nasal blockage" (82%), "postnasal discharge" (40%), "thick nasal discharge" (37%), and "wake up at night" (26%); 82%, 61%, 32%, 40%, and 26% of patients reported severe symptoms (score 4 or 5) for these items, respectively. Dupilumab improved score severity for all top 5 items versus placebo at W24 and W52. Improvements in NPS and LMK scores were numerically greater in patients with improvements in the SNOT-22 top 5 items. CONCLUSION: Loss of smell/taste was ranked as the most important symptom by patients with CRSwNP. Dupilumab reduced the severity of the top 5 most important SNOT-22 items versus placebo, in parallel with improvements in objective disease measures. CLINICAL TRIAL REGISTRATION: SINUS-24 and SINUS-52 clinical trials were registered with ClinicalTrials.gov, identifiers NCT02912468 and NCT02898454, respectively.

A review of pomegranate supplementation: A promising remedial avenue for Alzheimer's disease.

Neurodegenerative complications, like Alzheimer's disease (AD) exert adverse effects i.e. psychological and physiological in the central nervous system. The synthetic drugs used for these complications have negative effects on body health and therefore natural remedies are a good and targeted approach to counter such complications. Alternatively, fruits and a variety of biochemicals which are an important source of diet, can be used for remedial purposes. Due to the antioxidant properties of polyphenolic compounds, several companies utilize this property to advertise polyphenol-rich beverages. Pomegranate (Punica granatum L.), is one such fruit that is well known for its medical usage due to its antioxidant properties. In the cuurent study a literature search survey was performed on traditional uses, phytochemicals on pomegranate and their medical applications especaily in neurodegenerative deasese using electronic data bases like PubMed, Google Scholar, Scopus, Science Direct Wikipedia and Springer Nature. Based on previous preclinical and clinical studies, pomegranate juice, extracts, and its bioactive constituents have shown many mitigating properties, including suppression of inflammatory cell signaling, reduction in expression of genes associated with oxidative stress as well as pro-inflammatory cytokines in neurons, decreased production of inflammatory and oxidative stress biomarkers and increased expression of endothelial nitric oxide synthase. It also decreases the expression of soluble amyloid protein procurer ß (sAPPß), ß-secretase and carboxyl terminal fragment ß (CTFß). Similarly, during an in-vivo study on APP/PS1 mice, pomegranate supplementation has been shown to impart cognitive aid by the protection of neurons and triggering neurogenesis through anti-inflammatory signaling pathway. In conclusion, pomegranate supplementation can be a promising source of protection against Alzheimer's disease.

Edge Computing for Effective and Efficient Traffic Characterization.

Traffic flow analysis is essential to develop smart urban mobility solutions. Although numerous tools have been proposed, they employ only a small number of parameters. To overcome this limitation, an edge computing solution is proposed based on nine traffic parameters, namely, vehicle count, direction, speed, and type, flow, peak hour factor, density, time headway, and distance headway. The proposed low-cost solution is easy to deploy and maintain. The sensor node is comprised of a Raspberry Pi 4, Pi camera, Intel Movidius Neural Compute Stick 2, Xiaomi MI Power Bank, and Zong 4G Bolt+. Pre-trained models from the OpenVINO Toolkit are employed for vehicle detection and classification, and a centroid tracking algorithm is used to estimate vehicle speed. The measured traffic parameters are transmitted to the ThingSpeak cloud platform via 4G. The proposed solution was field-tested for one week (7 h/day), with approximately 10,000 vehicles per day. The count, classification, and speed accuracies obtained were 79.8%, 93.2%, and 82.9%, respectively. The sensor node can operate for approximately 8 h with a 10,000 mAh power bank and the required data bandwidth is 1.5 MB/h. The proposed edge computing solution overcomes the limitations of existing traffic monitoring systems and can work in hostile environments.

A new efficient referential genome compression technique for FastQ files.

Hospitals and medical laboratories create a tremendous amount of genome sequence data every day for use in research, surgery, and illness diagnosis. To make storage comprehensible, compression is therefore essential for the storage, monitoring, and distribution of all these data. A novel data compression technique is required to reduce the time as well as the cost of storage, transmission, and data processing. General-purpose compression techniques do not perform so well for these data due to their special features: a large number of repeats (tandem and palindrome), small alphabets, and highly similar, and specific file formats. In this study, we provide a method for compressing FastQ files that uses a reference genome as a backup without sacrificing data quality. FastQ files are initially split into three streams (identifier, sequence, and quality score), each of which receives its own compression technique. A novel quick and lightweight mapping mechanism is also presented to effectively compress the sequence stream. As shown by experiments, the suggested methods, both the compression ratio and the compression/decompression duration of NGS data compressed using RBFQC, are superior to those achieved by other state-of-the-art genome compression methods. In comparison to GZIP, RBFQC may achieve a compression ratio of 80-140% for fixed-length datasets and 80-125% for variable-length datasets. Compared to domain-specific FastQ file referential genome compression techniques, RBFQC has a compression and decompression speed (total) improvement of 10-25%.

Lactobacillus rhamnosus Attenuates Cisplatin-Induced Intestinal Mucositis in Mice via Modulating the Gut Microbiota and Improving Intestinal Inflammation.

Lactobacillus rhamnosus (LBS) is a well-documented probiotic strain in oncology and has a pivotal role in clinical applications. Here, we have investigated the protective effect of Lactobacillus rhamnosus on intestinal mucositis induced by cisplatin (CP) and explored the underlying mechanisms targeting inflammatory proteins, as well as the histological changes in the intestinal tissue of mice, in addition, the bacterial strains that may be related to the health-enhancing properties. BALB/c mice were pre-treated with or without LBS via oral gavage, followed by mucositis induction with cisplatin. Our results revealed that the LBS-treated groups significantly attenuated proinflammatory cytokine levels (IL-1ß, IL-6, and TNF-α) compared to the CP group. Furthermore, LBS mitigated the damaged tight junction integrity caused by CP via up-regulating the levels of claudin, occludin, ZO-1, and mucin-2 protein (MUC-2). Finally, the 16S rRNA fecal microbiome genomic analysis showed that LBS administration enhanced the growth of beneficial bacteria, i.e., Firmicutes and Lachnospiraceae, while the relative abundance of the opportunistic bacteria Bacteroides and Proteobacteria decreased. Collectively, LBS was found to beneficially modulate microbial composition structure and functions and enrich the ecological diversity in the gut.

Tear film proteome changes following Tobradex® therapy in anterior blepharitis.

PURPOSE: The management of blepharitis continues to challenge clinicians due to the poorly understood aetiology of the condition. We recently identified the family of intracellular plakin proteins as essential driving forces underlying anterior blepharitis. A large-scale protein analysis was used to study if a topical dexamethasone/tobramycin solution could be used to reverse the expression of plakin proteins. METHODS: Tear film samples from treatment naïve patients with anterior blepharitis (n = 15) were collected with Schirmer filtration paper. A subgroup of the patients (n = 10) received treatment with a dexamethasone/tobramycin 1 + 3 mg/mL ophthalmic suspension (Tobradex® ) for 3 weeks and collection of tear film samples was repeated. The samples were analysed with label-free quantification nano liquid chromatography-tandem mass spectrometry requiring quantification in at least 70% of the samples in each group. Proteins were considered differentially expressed if p < 0.05. RESULTS: Following Tobradex® intervention, 27 proteins were upregulated while 61 proteins were downregulated. Regulated proteins after Tobradex® treatment were involved in intermediate filament cytoskeleton organization including downregulation of the plakin proteins envoplakin, epiplakin and periplakin. Plectin, a protein of the plakin family, remained unchanged after Tobradex® therapy. Tobradex® treatment resulted in the regulation of proteins involved in translation including a cluster of downregulated ribosomal proteins. Tobradex® intervention was associated with the regulation of proteins involved in fructose metabolism and glycolytic processes including fructose-1.6-bisphosphatase 1, fructose-bisphosphate aldolases A and B, pyruvate kinase PKM and transketolase. Ig lambda chain V-I region, prominin-1, and protein Niban were upregulated after Tobradex® treatment. CONCLUSIONS: Tobradex treatment reversed the expression of plakin proteins in anterior blepharitis. Topical solutions which inhibit the expression of plakin proteins may have the potential to restore the ocular surface integrity in anterior blepharitis and should be explored further.