Deregulated transcription factors in the emerging cancer hallmarks.

Cancer progression is a multifaceted process that entails several stages and demands the persistent expression or activation of transcription factors (TFs) to facilitate growth and survival. TFs are a cluster of proteins with DNA-binding domains that attach to promoter or enhancer DNA strands to start the transcription of genes by collaborating with RNA polymerase and other supporting proteins. They are generally acknowledged as the major regulatory molecules that coordinate biological homeostasis and the appropriate functioning of cellular components, subsequently contributing to human physiology. TFs proteins are crucial for controlling transcription during the embryonic stage and development, and the stability of different cell types depends on how they function in different cell types. The development and progression of cancer cells and tumors might be triggered by any anomaly in transcription factor function. It has long been acknowledged that cancer development is accompanied by the dysregulated activity of TF alterations which might result in faulty gene expression. Recent studies have suggested that dysregulated transcription factors play a major role in developing various human malignancies by altering and rewiring metabolic processes, modifying the immune response, and triggering oncogenic signaling cascades. This review emphasizes the interplay between TFs involved in metabolic and epigenetic reprogramming, evading immune attacks, cellular senescence, and the maintenance of cancer stemness in cancerous cells. The insights presented herein will facilitate the development of innovative therapeutic modalities to tackle the dysregulated transcription factors underlying cancer.

Exploiting transcription factors to target EMT and cancer stem cells for tumor modulation and therapy.

Transcription factors (TFs) are essential in controlling gene regulatory networks that determine cellular fate during embryogenesis and tumor development. TFs are the major players in promoting cancer stemness by regulating the function of cancer stem cells (CSCs). Understanding how TFs interact with their downstream targets for determining cell fate during embryogenesis and tumor development is a critical area of research. CSCs are increasingly recognized for their significance in tumorigenesis and patient prognosis, as they play a significant role in cancer initiation, progression, metastasis, and treatment resistance. However, traditional therapies have limited effectiveness in eliminating this subset of cells, allowing CSCs to persist and potentially form secondary tumors. Recent studies have revealed that cancer cells and tumors with CSC-like features also exhibit genes related to the epithelial-to-mesenchymal transition (EMT). EMT-associated transcription factors (EMT-TFs) like TWIST and Snail/Slug can upregulate EMT-related genes and reprogram cancer cells into a stem-like phenotype. Importantly, the regulation of EMT-TFs, particularly through post-translational modifications (PTMs), plays a significant role in cancer metastasis and the acquisition of stem cell-like features. PTMs, including phosphorylation, ubiquitination, and SUMOylation, can alter the stability, localization, and activity of EMT-TFs, thereby modulating their ability to drive EMT and stemness properties in cancer cells. Although targeting EMT-TFs holds potential in tackling CSCs, current pharmacological approaches to do so directly are unavailable. Therefore, this review aims to explore the role of EMT- and CSC-TFs, their connection and impact in cellular development and cancer, emphasizing the potential of TF networks as targets for therapeutic intervention.

Signaling networks guiding erythropoiesis.

PURPOSE OF REVIEW: Cytokine-mediated signaling pathways, including JAK/STAT, PI3K/AKT, and Ras/MAPK pathways, play an important role in the process of erythropoiesis. These pathways are involved in the survival, proliferation, and differentiation function of erythropoiesis. RECENT FINDINGS: The JAK/STAT pathway controls erythroid progenitor differentiation, proliferation, and survival. The PI3K/AKT signaling cascade facilitates erythroid progenitor survival, proliferation, and final differentiation. During erythroid maturation, MAPK, triggered by EPO, suppresses myeloid genes, while PI3K is essential for differentiation. Pro-inflammatory cytokines activate signaling pathways that can alter erythropoiesis like EPOR-triggered signaling, including survival, differentiation, and proliferation. SUMMARY: A comprehensive understanding of signaling networks is crucial for the formulation of treatment approaches for hematologic disorders. Further investigation is required to fully understand the mechanisms and interactions of these signaling pathways in erythropoiesis.

After surgically induced remission, ileal and colonic mucosa-associated microbiota predicts Crohn's disease recurrence.

BACKGROUND AND AIMS: Investigating the tissue-associated microbiota after surgically induced remission may help to understand the mechanisms initiating intestinal inflammation in Crohn's disease. METHODS: Crohn's disease patients undergoing ileocolic resection were prospectively recruited in six academic centers. Biopsy samples from the neoterminal ileum, colon and rectosigmoid were obtained from colonoscopies performed after surgery. Microbial DNA was extracted for 16S rRNA gene sequencing. Microbial diversity and taxonomic differential relative abundance were analyzed. A random forest model was applied to analyze the performance of clinical and microbial features to predict recurrence. A Rutgeerts score ≥i2 was deemed as endoscopic recurrence. RESULTS: A total of 349 postoperative colonoscopies and 944 biopsy samples from 262 Crohn's disease patients were analyzed. Ileal inflammation accounted for most of the explained variance of the ileal and colonic mucosa-associated microbiota. Samples obtained from 97 patients who were in surgically induced remission at first postoperative colonoscopy who went on to develop endoscopic recurrence at second colonoscopy showed lower diversity and microbial deviations when compared to patients who remained in endoscopic remission. Depletion of genus Anaerostipes and increase of several genera from class Gammaproteobacteria at the three biopsy sites increase the risk of further recurrence. Gut microbiome was able to predict future recurrence better than clinical features. CONCLUSION: Ileal and colonic mucosa-associated microbiome deviations precede development of new onset ileal inflammation after surgically induced remission and show good predictive performance for future recurrence. These findings suggest that targeted microbial modulation is a plausible modality to prevent postoperative Crohn's disease recurrence.

Uniting Synergistic Effect of Single-Ni Site and Electric Field of B- Bridged-N for Boosted Electrocatalytic Nitrate Reduction to Ammonia.

Electrochemical conversion of nitrate, a prevalent water pollutant, to ammonia (NH3 ) is a delocalized and green path for NH3 production. Despite the existence of different nitrate reduction pathways, selectively directing the reaction pathway on the road to NH3 is now hindered by the absence of efficient catalysts. Single-atom catalysts (SACs) are extensively investigated in a wide range of catalytic processes. However, their application in electrocatalytic nitrate reduction reaction (NO3 - RR) to NH3 is infrequent, mostly due to their pronounced inclination toward hydrogen evolution reaction (HER). Here, Ni single atoms on the electrochemically active carrier boron, nitrogen doped-graphene (BNG) matrix to modulate the atomic coordination structure through a boron-spanning strategy to enhance the performance of NO3 - RR is designed. Density functional theory (DFT) study proposes that BNG supports with ionic characteristics, offer a surplus electric field effect as compared to N-doped graphene, which can ease the nitrate adsorption. Consistent with the theoretical studies, the as-obtained NiSA@BNG shows higher catalytic activity with a maximal NH3 yield rate of 168 µg h-1  cm-2 along with Faradaic efficiency of 95% and promising electrochemical stability. This study reveals novel ways to rationally fabricate SACs' atomic coordination structure with tunable electronic properties to enhance electrocatalytic performance.

Determining epitope specificity of T-cell receptors with transformers.

SUMMARY: T-cell receptors (TCRs) on T cells recognize and bind to epitopes presented by the major histocompatibility complex in case of an infection or cancer. However, the high diversity of TCRs, as well as their unique and complex binding mechanisms underlying epitope recognition, make it difficult to predict the binding between TCRs and epitopes. Here, we present the utility of transformers, a deep learning strategy that incorporates an attention mechanism that learns the informative features, and show that these models pre-trained on a large set of protein sequences outperform current strategies. We compared three pre-trained auto-encoder transformer models (ProtBERT, ProtAlbert, and ProtElectra) and one pre-trained auto-regressive transformer model (ProtXLNet) to predict the binding specificity of TCRs to 25 epitopes from the VDJdb database (human and murine). Two additional modifications were performed to incorporate gene usage of the TCRs in the four transformer models. Of all 12 transformer implementations (four models with three different modifications), a modified version of the ProtXLNet model could predict TCR-epitope pairs with the highest accuracy (weighted F1 score 0.55 simultaneously considering all 25 epitopes). The modification included additional features representing the gene names for the TCRs. We also showed that the basic implementation of transformers outperformed the previously available methods, i.e. TCRGP, TCRdist, and DeepTCR, developed for the same biological problem, especially for the hard-to-classify labels. We show that the proficiency of transformers in attention learning can be made operational in a complex biological setting like TCR binding prediction. Further ingenuity in utilizing the full potential of transformers, either through attention head visualization or introducing additional features, can extend T-cell research avenues. AVAILABILITY AND IMPLEMENTATION: Data and code are available on https://github.com/InduKhatri/tcrformer.

Soybean-mediated suppression of BjaI/BjaR1 quorum sensing in Bradyrhizobium diazoefficiens impacts symbiotic nitrogen fixation.

The acyl-homoserine lactones (AHLs)-mediated LuxI/LuxR quorum sensing (QS) system orchestrates diverse bacterial behaviors in response to changes in population density. The role of the BjaI/BjaR1 QS system in Bradyrhizobium diazoefficiens USDA 110, which shares homology with LuxI/LuxR, remains elusive during symbiotic interaction with soybean. Here this genetic system in wild-type (WT) bacteria residing inside nodules exhibited significantly reduced activity compared to free-living cells, potentially attributed to soybean-mediated suppression. The deletion mutant strain ΔbjaR1 showed significantly enhanced nodulation induction and nitrogen fixation ability. Nevertheless, its ultimate symbiotic outcome (plant dry weight) in soybeans was compromised. Furthermore, comparative analysis of the transcriptome, proteome, and promoter activity revealed that the inactivation of BjaR1 systematically activated and inhibited genomic modules associated with nodulation and nitrogen metabolism. The former appeared to be linked to a significant decrease in the expression of NodD2, a key cell-density-dependent repressor of nodulation genes, while the latter conferred bacterial growth and nitrogen fixation insensitivity to environmental nitrogen. In addition, BjaR1 exerted a positive influence on the transcription of multiple genes involved in a so-called central intermediate metabolism within the nodule. In conclusion, our findings highlight the crucial role of the BjaI/BjaR1 QS circuit in positively regulating bacterial nitrogen metabolism and emphasize the significance of the soybean-mediated suppression of this genetic system for promoting efficient symbiotic nitrogen fixation by B. diazoefficiens.IMPORTANCEThe present study demonstrates, for the first time, that the BjaI/BjaR1 QS system of Bradyrhizobium diazoefficiens has a significant impact on its nodulation and nitrogen fixation capability in soybean by positively regulating NodD2 expression and bacterial nitrogen metabolism. Moreover, it provides novel insights into the importance of suppressing the activity of this QS circuit by the soybean host plant in establishing an efficient mutual relationship between the two symbiotic partners. This research expands our understanding of legumes' role in modulating symbiotic nitrogen fixation through rhizobial QS-mediated metabolic functioning, thereby deepening our comprehension of symbiotic coevolution theory. In addition, these findings may hold great promise for developing quorum quenching technology in agriculture.

Repressive H3K27me3 drives hyperglycemia-induced oxidative and inflammatory transcriptional programs in human endothelium.

BACKGROUND: Histone modifications play a critical role in chromatin remodelling and regulate gene expression in health and disease. Histone methyltransferases EZH1, EZH2, and demethylases UTX, JMJD3, and UTY catalyse trimethylation of lysine 27 on histone H3 (H3K27me3). This study was designed to investigate whether H3K27me3 triggers hyperglycemia-induced oxidative and inflammatory transcriptional programs in the endothelium. METHODS: We studied human aortic endothelial cells exposed to high glucose (HAEC) or isolated from individuals with diabetes (D-HAEC). RT-qPCR, immunoblotting, chromatin immunoprecipitation (ChIP-qPCR), and confocal microscopy were performed to investigate the role of H3K27me3. We determined superoxide anion (O2-) production by ESR spectroscopy, NF-κB binding activity, and monocyte adhesion. Silencing/overexpression and pharmacological inhibition of chromatin modifying enzymes were used to modulate H3K27me3 levels. Furthermore, isometric tension studies and immunohistochemistry were performed in aorta from wild-type and db/db mice. RESULTS: Incubation of HAEC to high glucose showed that upregulation of EZH2 coupled to reduced demethylase UTX and JMJD3 was responsible for the increased H3K27me3. ChIP-qPCR revealed that repressive H3K27me3 binding to superoxide dismutase and transcription factor JunD promoters is involved in glucose-induced O2- generation. Indeed, loss of JunD transcriptional inhibition favours NOX4 expression. Furthermore, H3K27me3-driven oxidative stress increased NF-κB p65 activity and downstream inflammatory genes. Interestingly, EZH2 inhibitor GSK126 rescued these endothelial derangements by reducing H3K27me3. We also found that H3K27me3 epigenetic signature alters transcriptional programs in D-HAEC and aortas from db/db mice. CONCLUSIONS: EZH2-mediated H3K27me3 represents a key epigenetic driver of hyperglycemia-induced endothelial dysfunction. Targeting EZH2 may attenuate oxidative stress and inflammation and, hence, prevent vascular disease in diabetes.

Unveiling the Therapeutic Potential of Non-Coding RNAs in Stroke-Induced Tissue Regeneration.

Stroke is a major contributor to mortality and impairment on a global scale, with few effective treatments available. Aberrant expression of various non-coding RNAs (ncRNAs) has been identified after stroke onset, impacting neurogenesis, angiogenesis, apoptosis, and autophagy. The roles and mechanisms of ncRNAs hold great promise for future ischemic stroke treatments, as they could modify stroke impact and course on a well-controllable molecular level. Exploring the functions and underlying mechanisms of ncRNAs after stroke has the potential to unveil novel therapeutic targets for the treatment of stroke and may also pave the way toward novel and more precise diagnostic options for stroke and stroke outcomes. This review emphasizes the importance of ncRNAs in the treatment of stroke and their potential as therapeutic targets.

MCC950 reduces autophagy and improves cognitive function by inhibiting NLRP3-dependent neuroinflammation in a rat model of Alzheimer's disease.

Alzheimer's disease (AD) is the seventh most common cause of mortality and one of the major causes of disability and vulnerability in the elderly. AD is characterized by gradual cognitive deterioration, the buildup of misfolded amyloid beta (Aß) peptide, and the generation of neurofibrillary tangles. Despite enormous scientific progress, there is no effective cure for AD. Thus, exploring new treatment options to stop AD or at least slow down its progress is important. In this study, we investigated the potential therapeutic effects of MCC950 on NLRP3-mediated inflammasome-driven inflammation and autophagy in AD. Rats treated with streptozotocin (STZ) exhibited simultaneous activation of the NLRP3 inflammasome and autophagy, as confirmed by Western blot, immunofluorescence, and co-immunoprecipitation analyses. MCC950, a specific NLRP3 inhibitor, was intraperitoneally administered (50 mg/kg body weight) to rats with AD-like symptoms induced by intracerebroventricular STZ injections (3 mg/kg body weight). MCC950 effectively suppressed STZ-induced cognitive impairment and anxiety by inhibiting NLRP3-dependent neuroinflammation. Moreover, our findings indicate that MCC950 exerts neuroprotective effects by attenuating autophagy in neuronal cells. The inhibiting effects of MCC950 on inflammasome activation and autophagy were reproduced in vitro, provding further mechansistic insights into MCC950 therapeutic action. Our findings suggest that MCC950 impedes the progression of AD and may also improve cognitive function through the mitigation of autophagy and NLRP3 inflammasome inhibition.

Prevalence and Trajectories of Post-COVID-19 Neurological Manifestations: A Systematic Review and Meta-Analysis.

INTRODUCTION: The aim of this systematic review and meta-analysis was to evaluate the prevalence of thirteen neurological manifestations in people affected by COVID-19 during the acute phase and at 3, 6, 9 and 12-month follow-up time points. METHODS: The study protocol was registered with PROSPERO (CRD42022325505). MEDLINE (PubMed), Embase, and the Cochrane Library were used as information sources. Eligible studies included original articles of cohort studies, case-control studies, cross-sectional studies, and case series with ≥5 subjects that reported the prevalence and type of neurological manifestations, with a minimum follow-up of 3 months after the acute phase of COVID-19 disease. Two independent reviewers screened studies from January 1, 2020, to June 16, 2022. The following manifestations were assessed: neuromuscular disorders, encephalopathy/altered mental status/delirium, movement disorders, dysautonomia, cerebrovascular disorders, cognitive impairment/dementia, sleep disorders, seizures, syncope/transient loss of consciousness, fatigue, gait disturbances, anosmia/hyposmia, and headache. The pooled prevalence and their 95% confidence intervals were calculated at the six pre-specified times. RESULTS: 126 of 6,565 screened studies fulfilled the eligibility criteria, accounting for 1,542,300 subjects with COVID-19 disease. Of these, four studies only reported data on neurological conditions other than the 13 selected. The neurological disorders with the highest pooled prevalence estimates (per 100 subjects) during the acute phase of COVID-19 were anosmia/hyposmia, fatigue, headache, encephalopathy, cognitive impairment, and cerebrovascular disease. At 3-month follow-up, the pooled prevalence of fatigue, cognitive impairment, and sleep disorders was still 20% and higher. At six- and 9-month follow-up, there was a tendency for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache to further increase in prevalence. At 12-month follow-up, prevalence estimates decreased but remained high for some disorders, such as fatigue and anosmia/hyposmia. Other neurological disorders had a more fluctuating occurrence. DISCUSSION: Neurological manifestations were prevalent during the acute phase of COVID-19 and over the 1-year follow-up period, with the highest overall prevalence estimates for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache. There was a downward trend over time, suggesting that neurological manifestations in the early post-COVID-19 phase may be long-lasting but not permanent. However, especially for the 12-month follow-up time point, more robust data are needed to confirm this trend.

Telluride-Based Materials: A Promising Route for High Performance Supercapacitors.

As supercapacitor (SC) technology continues to evolve, there is a growing need for electrode materials with high energy/power densities and cycling stability. However, research and development of electrode materials with such characteristics is essential for commercialization the SC. To meet this demand, the development of superior electrode materials has become an increasingly critical step. The electrochemical performance of SCs is greatly influenced by various factors such as the reaction mechanism, crystal structure, and kinetics of electron/ion transfer in the electrodes, which have been challenging to address using previously investigated electrode materials like carbon and metal oxides/sulfides. Recently, tellurium and telluride-based materials have garnered increasing interest in energy storage technology owing to their high electronic conductivity, favorable crystal structure, and excellent volumetric capacity. This review provides a comprehensive understanding of the fundamental properties and energy storage performance of tellurium- and Te-based materials by introducing their physicochemical properties. First, we elaborate on the significance of tellurides. Next, the charge storage mechanism of functional telluride materials and important synthesis strategies are summarized. Then, research advancements in metal and carbon-based telluride materials, as well as the effectiveness of tellurides for SCs, were analyzed by emphasizing their essential properties and extensive advantages. Finally, the remaining challenges and prospects for improving the telluride-based supercapacitive performance are outlined.

Effectiveness of locally produced ready-to-use supplementary foods on the prevention of stunting in children aged 6-23 months: a community-based trial from Pakistan.

Undernutrition is a major public health problem in developing countries. Around 40·2 % of children are stunted in Pakistan. This longitudinal study aimed to assess the effectiveness of locally produced ready-to-use supplementary foods in the prevention of stunting by detecting change in of children in intervention v. control arm against the 2006 WHO growth reference. A community-based non-randomised cluster-controlled trial was conducted from January 2018 to December 2020 in the district of Kurram, Khyber Pakhtunkhwa, Pakistan. A total of 80 clusters (each cluster comprising ≈ 250-300 households) were defined in the catchment population of twelve health facilities. Children aged 6-18 months were recruited n 1680. The intervention included a daily ration of 50 g - locally produced ready-to-use-supplementary food (Wawa-Mum). The main outcome of this study was a change in length for age z-score (LAZ) v. WHO growth standards. Comparison between the interventions was by t test and ANOVA. Cox proportional hazard models were used to assess the association between stunting occurrence and the utilisation of locally produced supplement. Out of the total 1680, fifty-one out of the total 1680, 51·1 out of the total 1680 and 51·1 % (n 859) were male. Mean age 13·9 months (sd + 859) were male. Mean age 13·9 months (sd + -4·4). At baseline, 36·9 % (n 618) were stunted. In the intervention group, mean LAZ score significantly increased from -1·13(2·2 sd) at baseline to -0·93(1·8 sd) at 6-month follow-up (P value 0·01) compared with the control group. The incidence rate of stunting in the intervention arm was 1·3 v. 3·4 per person year in the control arm. The control group had a significantly increased likelihood of stunting (Hazard Ratio (HR) 1·7, 95 % CI 1·46, 2·05, P value < 0·001) v. the intervention group. Locally produced ready-to-use supplementary food is an effective intervention for reducing stunting in children below 2 years of age. This can be provided as part of a malnutrition prevention package to overcome the alarming rates of stunting in Pakistan.

Kidney Injury by Unilateral Ureteral Obstruction in Mice Lacks Sex Differences.

INTRODUCTION: Renal fibrosis is a critical event in the development and progression of chronic kidney disease (CKD), and it is considered the final common pathway for all types of CKD. The prevalence of CKD is higher in females; however, males have a greater prevalence of end-stage renal disease. In addition, low birth weight and low nephron number are associated with increased risk for CKD. This study examined the development and severity of unilateral ureter obstruction (UUO)-induced renal fibrosis in male and female wild-type (ROP +/+) and mutant (ROP Os/+) mice, a mouse model of low nephron number. METHODS: Male and female ROP +/+ and ROP Os/+ mice were subjected to UUO, and kidney tissue was collected at the end of the 10-day experimental period. Kidney histological analysis and mRNA expression determined renal fibrosis, tubular injury, collagen deposition, extracellular matrix proteins, and immune cell infiltration. RESULTS: Male and female UUO mice demonstrated marked renal injury, kidney fibrosis, and renal extracellular matrix production. Renal fibrosis and α-smooth muscle actin were increased to a similar degree in ROP +/+ and ROP Os/+ mice with UUO of either sex. There were also no sex differences in renal tubular cast formation or renal infiltration of macrophage in ROP +/+ and ROP Os/+ UUO mice. Interestingly, renal fibrosis and α-smooth muscle actin were 1.5-3-fold greater in UUO-ROP +/+ compared to UUO-ROP Os/+ mice. Renal inflammation phenotypes following UUO were also 30-45% greater in ROP +/+ compared to ROP Os/+ mice. Likewise, expression of extracellular matrix and renal fibrotic genes was greater in UUO-ROP +/+ mice compared to UUO-ROP Os/+ mice. In contrast to these findings, ROP Os/+ mice with UUO demonstrated glomerular hypertrophy with 50% greater glomerular tuft area compared to ROP +/+ with UUO. Glomerular hypertrophy was not sex-dependent in any of the genotypes of ROP mice. These findings provide evidence that low nephron number contributes to UUO-induced glomerular hypertrophy in ROP Os/+ mice but does not enhance renal fibrosis, inflammation, and renal tubular injury. CONCLUSION: Taken together, we demonstrate that low nephron number contributes to enhanced glomerular hypertrophy but not kidney fibrosis and tubular injury. We also demonstrate that none of the changes caused by UUO was affected by sex in any of the ROP mice genotypes.

NMR based Serum metabolomics revealed metabolic signatures associated with oxidative stress and mitochondrial damage in brain stroke.

Brain stroke (BS, also known as a cerebrovascular accident), represents a serious global health crisis. It has been a leading cause of permanent disability and unfortunately, frequent fatalities due to lack of timely medical intervention. While progress has been made in prevention and management, the complexities and consequences of stroke continue to pose significant challenges, especially, its impact on patient's quality of life and independence. During stroke, there is a substantial decrease in oxygen supply to the brain leading to alteration of cellular metabolic pathways, including those involved in mitochondrial-damage, leading to mitochondrial-dysfunction. The present proof-of-the-concept metabolomics study has been performed to gain insights into the metabolic pathways altered following a brain stroke and discover new potential targets for timely interventions to mitigate the effects of cellular and mitochondrial damage in BS. The serum metabolic profiles of 108 BS-patients were measured using 800 MHz NMR spectroscopy and compared with 60 age and sex matched normal control (NC) subjects. Compared to NC, the serum levels of glutamate, TCA-cycle intermediates (such as citrate, succinate, etc.), and membrane metabolites (betaine, choline, etc.) were found to be decreased BS patients, whereas those of methionine, mannose, mannitol, phenylalanine, urea, creatine and organic acids (such as 3-hydroxybutyrate and acetone) were found to be elevated in BS patients. These metabolic changes hinted towards hypoxia mediated mitochondrial dysfunction in BS-patients. Further, the area under receiver operating characteristic curve (ROC) values for five metabolic features (methionine, mannitol, phenylalanine, mannose and urea) found to be more than 0.9 suggesting their high sensitivity and specificity for differentiating BS from NC subjects.

A Novel Coated Suture Displays Antimicrobial Activity Without Compromising Structural Properties.

BACKGROUND: Treated or coated sutures promise to prevent contamination of wounds. PURPOSE: The purpose of the study was to coat surgical sutures with a new quaternary ammonium silane (QAS) antimicrobial compound at two different application temperatures and then to evaluate the resulting structural, physical, mechanical, and biological properties. STUDY DESIGN, SETTING, SAMPLE: In vitro and in vivo studies were conducted using male albino Wistar rats approved by the Joint Ethical Committee of IMU and Postgraduate Medical Institute, Lahore. Only suture samples, coated uniformly with verified presence of the compound and of adequate length were used. Samples which were not coated uniformly and with inadequate length or damaged were excluded. PREDICTOR VARIABLE: Predictor variables were sutures with and without QAS coatings and different temperatures. Sutures were coated with QAS at 0.5 and 1.0% wt/vol using the dip coating technique and sutures with and without QAS coating were tested at 25 and 40 °C temperatures. MAIN OUTCOME VARIABLE(S): Outcome variables of structural and physico-mechanical properties of QAS-coated and non-coated sutures were measured using Fourier transform infrared spectroscopy (for structural changes), confocal laser and scanning electron (for diameter changes), and tensile strength/modulus (for mechanical testing). Biologic outcome variables were tested (bacterial viability); macrophage cultures from Wistar rats were tested (M1/M2 polarization detecting IL-6 and IL-10). Macrophage cells were analyzed with CD80+ (M1) and CD163+ (M2). Chemotaxis index was calculated as a ratio of quantitative fluorescence of cells. COVARIATES: Not applicable. ANALYSES: Ordinal data among groups were compared using the Wilcoxon Mann-Whitney U test along with the comparison of histological analysis using the Wilcoxon Sign-rank test (P < .05). RESULTS: Fourier transform infrared spectroscopy peak at 1490 cm-1 confirmed the presence of QAS on suture's surfaces with a significant increase (P < .05) in diameter (0.99 ± 0.5-mm) and weight (0.77 ± 0.02-mg) observed for 1% QAS groups treated at 40 °C. Non-coated samples heated at 25 °C had significantly (P < .05) less diameters (0.22 ± 0.03-mm) and weights (0.26 ± 0.06-mg). Highest tensile strength/modulus was observed for 0.5% QAS-coated samples which also had significantly higher antibacterial characteristics than other sutures (P < .05). QAS-coated sutures significantly increased M1 and M2 markers. CONCLUSION AND RELEVANCE: QAS coating conferred antibacterial action properties without compromising the physical and mechanical properties of the suture.

Non-Invasive Multi-Gas Detection Enabled by Cu-CuO/PEDOT Microneedle Sensor.

Metal-oxide-based gas sensors are extensively utilized across various domains due to their cost-effectiveness, facile fabrication, and compatibility with microelectronic technologies. The copper (Cu)-based multifunctional polymer-enhanced sensor (CuMPES) represents a notably tailored design for non-invasive environmental monitoring, particularly for detecting diverse gases with a low concentration. In this investigation, the Cu-CuO/PEDOT nanocomposite was synthesized via a straightforward chemical oxidation and vapor-phase polymerization. Comprehensive characterizations employing X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), X-ray diffraction (XRD), and micro Raman elucidated the composition, morphology, and crystal structure of this nanocomposite. Gas-sensing assessments of this CuMPES based on Cu-CuO/PEDOT revealed that the response current of the microneedle-type CuMPES surpassed that of the pure Cu microsensor by nearly threefold. The electrical conductivity and surface reactivity are enhanced by poly (3,4-ethylenedioxythiophene) (PEDOT) polymerized on the CuO-coated surface, resulting in an enhanced sensor performance with an ultra-fast response/recovery of 0.3/0.5 s.

A 5-year comprehensive evaluation of maxillofacial injuries in polytrauma patients at a tertiary hospital - an epidemiological study.

OBJECTIVES: To report and analyze the pattern of maxillofacial injuries in trauma victims and to define the role of a maxillofacial surgeon in an emergency trauma care team. MATERIALS AND METHODS: Trauma patients reported and reporting to the casualty of a tertiaryhospital with facial injuries and other suspected concomitant injuries in the body were included in this study. The complete medical and radiographic records of each patient were reviewed and data was collected in a standard proforma in this 5-year clinical study (3 year of retrospective and 2 year of prospective study). The complete data related to the facial injuries and associated systemic trauma was recorded and statistical analysis conducted. RESULTS: A total of 18,369 patients with trauma were admitted to the hospital from May 2018 to April 2023. Out of these, 11,277 (61.4%) were males and 7,092 (38.6%) were females. Seventy percent of the reported cases with trauma were in the age group of 14-40 years. The incidence of trauma during the monsoon season was highest (n = 7,927, 43%). The commonest etiological factor leading to trauma was road traffic accident (n = 4,510, 40%). Among facial injuries, the mandibular fractures (n = 1,821, 41%) were predominant. CONCLUSIONS: The management of polytrauma patients should be undertaken by a team of specialists which should include a maxillofacial surgeon as facial injuries were common. This data is essential in developing and assessing the preventative strategies aimed at decreasing the frequency of facial and other injuries.

Prevalence of obstructive sleep apnoea syndrome in oncological patients: A systematic review and meta-analysis.

BACKGROUND: Obstructive sleep apnoea syndrome (OSAS) has garnered increasing attention in recent years due to its potential association with cancer. This systematic review and meta-analysis aimed to assess the prevalence of OSAS in cancer patients through a comprehensive analysis of existing literature. METHODS: This systematic review and meta-analysis, conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, aimed to evaluate the prevalence of OSAS in cancer patients. A comprehensive search of electronic databases was performed to identify relevant studies published up to September 2021. Eligible studies reporting on the prevalence of OSAS in cancer patients, encompassing various study designs, were included in the analysis. Pooled estimates of the odds ratios (OR) with 95% confidence intervals (CIs) were calculated using a random effects model. Heterogeneity among the studies was assessed using the I2 statistic. RESULTS: Seventeen studies fulfilled the inclusion criteria and were subsequently included in the review. The prevalence of OSAS in cancer patients was estimated to have an overall OR of 0.80 (95% CI: 0.75-0.85). In comparison with non-cancer patients, cancer patients had a statistically significant greater risk of OSAS, as indicated by the total estimated RR for the prevalence of OSAS in cancer patients, which was 0.89 (95% CI: 0.86-0.92). Nonetheless, there was a significant amount of heterogeneity (I2 = 96%) among the studies. CONCLUSION: The overall data analysed in this review indicates that patients with cancer had far reduced likelihood of developing OSAS than individuals without cancer. However, the significant variation across the included studies highlights the need for additional investigation to fully clarify the complex association between OSAS and cancer incidence. These results emphasise how critical it is to identify OSAS as a possible comorbidity in cancer patients, one that should be taken into account for clinical management and ongoing research.

Epidemiology and Clinical Outcomes of Fusobacterium Infections: A Six-Year Retrospective Study.

Background and Objectives: Anaerobic bacteria like Fusobacterium can lead to severe and life-threatening infections. The inherent complexities in the isolation of these bacteria may result in diagnostic and therapeutic delays, thereby escalating both morbidity and mortality rates. We aimed to examine data from patients with infections due to Fusobacterium to gain insights into the epidemiology and clinical outcomes of patients with these infections. Methods and Results: We conducted a retrospective analysis of clinical data from a cohort of patients with cultures positive for Fusobacterium species at a tertiary care medical center in the United States. Between 2009 and 2015, we identified 96 patients with cultures positive for Fusobacterium. Patients could be categorized into three groups based on the site of primary infection. Patients with head and neck infections constituted 37% (n 36). Patients with infections of other soft tissue sites accounted for 38.5% (n 37). Patients with anaerobic bacteremia due to Fusobacterium formed 24% (n 23) of the cohort. Surgical intervention coupled with antibiotic therapy emerged as cornerstones of management for patients with head and neck or other soft tissue infections, who generally exhibited more favorable outcomes. Patients with bacteremia were older, more likely to have malignancy, and had a high mortality rate. When speciation was available, Fusobacterium necrophorum was the most frequently isolated species. Conclusions: Our retrospective analysis of epidemiology and clinical outcomes of Fusobacterium infections revealed three distinct cohorts. Patients with head, neck, or soft tissue infections had better outcomes than those with bacteremia. Our findings highlight the importance of employing management strategies based on infection site and underlying comorbidities in patients with Fusobacterium infections. Further research is needed to investigate the optimal therapeutic strategies and identify prognostic indicators to improve clinical outcomes for these complex infections.