Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial.

BACKGROUND: The optimal amount and timing of protein intake in critically ill patients are unknown. REPLENISH (Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial evaluates whether supplemental enteral protein added to standard enteral nutrition to achieve a high amount of enteral protein given from ICU day five until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve a moderate amount of enteral protein would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients. METHODS: In this multicenter randomized trial, critically ill patients will be randomized to receive supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition to achieve a high amount of enteral protein (range of 2-2.4 g/kg/day) or no supplemental enteral protein to achieve a moderate amount of enteral protein (0.8-1.2 g/kg/day). The primary outcome is 90-day all-cause mortality; other outcomes include functional and health-related quality-of-life assessments at 90 days. The study sample size of 2502 patients will have 80% power to detect a 5% absolute risk reduction in 90-day mortality from 30 to 25%. Consistent with international guidelines, this statistical analysis plan specifies the methods for evaluating primary and secondary outcomes and subgroups. Applying this statistical analysis plan to the REPLENISH trial will facilitate unbiased analyses of clinical data. CONCLUSION: Ethics approval was obtained from the institutional review board, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (RC19/414/R). Approvals were also obtained from the institutional review boards of each participating institution. Our findings will be disseminated in an international peer-reviewed journal and presented at relevant conferences and meetings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04475666 . Registered on July 17, 2020.

The Impact of Periodontal Inflammation on the Severity of Coronary Atherosclerosis.

Introduction Through plausible biological mechanisms, periodontitis causes systemic inflammatory burden and response, thus resulting in damage far beyond the oral cavity. Studies have demonstrated periodontitis to be a significant risk factor for coronary heart disease (CHD) and stroke. The larger the quantum of periodontal inflamed tissue, the greater the chances of periodontitis eliciting bacteremia and systemic inflammatory responses. Studies have reported that periodontitis and other common oral infections play an important role in the development of atherosclerosis. Therefore, the quantity of inflamed periodontal tissue assumes significance in determining the severity of atherosclerosis. Hence, this study investigates the impact of periodontal inflamed surface area (PISA) on the severity of coronary atherosclerosis. Materials and methods In this cross-sectional study, a total of 160 patients who presented at the department of periodontics of The British University in Egypt (BUE) from 1 January 2023 to 30 September 2023 were enrolled. Patients were only enrolled if they had undergone coronary angiography within the last six months, were less than 60 years of age, shared their previous medical history and coronary angiographic report, and gave informed written consent. Data on classic coronary risk factors and periodontal inflammatory status and angiographic findings were recorded and subjected to appropriate statistical analysis. Results The results revealed that the periodontal inflamed surface area (p = 0.002) apart from age (p < 0.047) and low-density lipoprotein cholesterol (LDL-C) (p < 0.001) is a significant independent predictor of the severity of coronary atherosclerosis. Conclusions The periodontal inflamed surface area is an independent predictor of the severity of coronary atherosclerosis.

Emergence of Long-Range Angular Correlations in Low-Multiplicity Proton-Proton Collisions.

This Letter presents the measurement of near-side associated per-trigger yields, denoted ridge yields, from the analysis of angular correlations of charged hadrons in proton-proton collisions at sqrt[s]=13 TeV. Long-range ridge yields are extracted for pairs of charged particles with a pseudorapidity difference of 1.4<|Δη|<1.8 and a transverse momentum of 1

Genomic analysis and phylogenetic characterization of Himalayan snow trout, Schizothorax esocinus based on mitochondrial protein-coding genes.

BACKGROUND: Mitochondrial DNA (mtDNA) has become a significant tool for exploring genetic diversity and delineating evolutionary links across diverse taxa. Within the group of cold-water fish species that are native to the Indian Himalayan region, Schizothorax esocinus holds particular importance due to its ecological significance and is potentially vulnerable to environmental changes. This research aims to clarify the phylogenetic relationships within the Schizothorax genus by utilizing mitochondrial protein-coding genes. METHODS: Standard protocols were followed for the isolation of DNA from S. esocinus. For the amplification of mtDNA, overlapping primers were used, and then subsequent sequencing was performed. The genetic features were investigated by the application of bioinformatic approaches. These approaches covered the evaluation of nucleotide composition, codon usage, selective pressure using nonsynonymous substitution /synonymous substitution (Ka/Ks) ratios, and phylogenetic analysis. RESULTS: The study specifically examined the 13 protein-coding genes of Schizothorax species which belongs to the Schizothoracinae subfamily. Nucleotide composition analysis showed a bias towards A + T content, consistent with other cyprinid fish species, suggesting evolutionary conservation. Relative Synonymous Codon Usage highlighted leucine as the most frequent (5.18%) and cysteine as the least frequent (0.78%) codon. The positive AT-skew and the predominantly negative GC-skew indicated the abundance of A and C. Comparative analysis revealed significant conservation of amino acids in multiple genes. The majority of amino acids were hydrophobic rather than polar. The purifying selection was revealed by the genetic distance and Ka/Ks ratios. Phylogenetic study revealed a significant genetic divergence between S. esocinus and other Schizothorax species with interspecific K2P distances ranging from 0.00 to 8.87%, with an average of 5.76%. CONCLUSION: The present study provides significant contributions to the understanding of mitochondrial genome diversity and genetic evolution mechanisms in Schizothoracinae, hence offering vital insights for the development of conservation initiatives aimed at protecting freshwater fish species.

First Measurement of the |t| Dependence of Incoherent J/ψ Photonuclear Production.

The first measurement of the cross section for incoherent photonuclear production of J/ψ vector mesons as a function of the Mandelstam |t| variable is presented. The measurement was carried out with the ALICE detector at midrapidity, |y|<0.8, using ultraperipheral collisions of Pb nuclei at a center-of-mass energy per nucleon pair of sqrt[s_{NN}]=5.02 TeV. This rapidity interval corresponds to a Bjorken-x range (0.3-1.4)×10^{-3}. Cross sections are given in five |t| intervals in the range 0.04<|t|<1 GeV^{2} and compared to the predictions by different models. Models that ignore quantum fluctuations of the gluon density in the colliding hadron predict a |t| dependence of the cross section much steeper than in data. The inclusion of such fluctuations in the same models provides a better description of the data.

Long COVID-19 and primary care: Challenges, management and recommendations / COVID-19 prolongado y atención primaria: desafíos, manejo y recomendaciones

Long COVID-19, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent symptoms after COVID-19 onset. This article explores the challenges, management strategies, and recommendations for addressing long COVID-19 in primary care settings. The epidemiology of long COVID-19 reveals significant variability, with a substantial portion of COVID-19 survivors experiencing post-acute symptoms. Pathophysiological mechanisms include viral persistence, endothelial dysfunction, autoimmunity, neurological dysregulation, and gastrointestinal dysbiosis. Multiple risk factors, including age, sex, pre-existing comorbidities, smoking, BMI, and acute COVID-19 severity, influence the development of long COVID-19. Effective management requires proactive measures such as vaccination, identification of high-risk populations, public awareness, and post-infection vaccination. Collaboration of primary care physicians with specialists is essential for holistic and individualized patient care. This article underscores the role of primary care physicians in diagnosing, managing, and mitigating the long-term effects of COVID-19. (AU)

La COVID-19 prolongada, también conocida como secuela postaguda de la infección por SARS-CoV-2, se caracteriza por síntomas persistentes después de la aparición de la COVID-19. Este artículo explora los desafíos, las estrategias de manejo y las recomendaciones para abordar la COVID-19 prolongada en entornos de atención primaria. La epidemiología de la COVID-19 prolongada revela una variabilidad significativa, y una parte sustancial de los supervivientes de la COVID-19 experimentan síntomas postagudos. Los mecanismos fisiopatológicos incluyen persistencia viral, disfunción endotelial, autoinmunidad, desregulación neurológica y disbiosis gastrointestinal. Múltiples factores de riesgo, como la edad, el sexo, las comorbilidades preexistentes, el tabaquismo, el IMC y la gravedad aguda de la COVID-19, influyen en el desarrollo de la COVID-19 prolongada. Una gestión eficaz requiere medidas proactivas, como la vacunación, la identificación de poblaciones de alto riesgo, la concienciación pública y la vacunación posterior a la infección. La colaboración de los médicos de atención primaria con los especialistas es esencial para una atención holística e individualizada al paciente. Este artículo subraya el papel de los médicos de atención primaria en el diagnóstico, el tratamiento y la mitigación de los efectos a largo plazo de la COVID-19. (AU)

Quinazoline sulfonamide derivatives targeting MicroRNA-34a/MDM4/p53 apoptotic axis with radiosensitizing activity.

Aim: New quinazoline benzenesulfonamide hybrids 4a-n were synthesized to determine their cytotoxicity and effect on the miR-34a/MDM4/p53 apoptotic pathway. Materials & methods: Cytotoxicity against hepatic, breast, lung and colon cancer cell lines was estimated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: Compound 4d was the most potent against HepG2 and MCF-7 cancer cells, with potential apoptotic activity verified by a significant upregulation of miR-34a and p53 gene expressions. The apoptotic effect of 4d was further investigated and showed downregulation of miR-21, VEGF, STAT3 and MDM4 gene expression. Conclusion: The anticancer and apoptotic activities of 4d were enhanced post irradiation by a single dose of 8 Gy γ-radiation. Docking analysis demonstrated a valuable affinity of 4d toward VEGFR2 and MDM4 active sites.

Dental and Periodontal Changes After Accelerated Correction of Lower Anterior Teeth Crowding With Periodontally Accelerated Osteogenic Orthodontics (PAOO) Procedure: A Randomized Controlled Trial.

Objective To evaluate the relative efficacy of periodontally accelerated osteogenic orthodontics (PAOO) compared to conventional fixed appliances in correcting lower anterior teeth crowding using a non-extraction treatment approach. Material and methods A single-center, two-arm, parallel-group randomized controlled trial was conducted on 38 patients (9 males, 29 females) with moderate crowding. These patients did not require premolar extraction and were randomly allocated into two treatment groups: the PAOO group and the conventional orthodontic treatment group. The Little Irregularity Index (LII) measured crowding intensity on pre-treatment study models. Changes in this index were recorded monthly in both treatment groups. The inter-canine width, inter-second-premolar width, plaque index (PI), gingival index (GI), and papillary bleeding index (PBI) were also measured before and after the leveling and alignment stage. Statistical analysis between the two groups was performed using Mann-Whitney U tests. Results For the LII, the average time for irregularity resolution was three months in the PAOO group, compared to five months in the conventional orthodontic treatment group. Regarding changes in inter-second-premolar width, the PAOO procedure led to a significant decrease in the increase of inter-second-premolar width, with an average increase of +1.52 mm compared to +2.71 mm in the control group. For the GI and PBI, it was found that their values significantly increased with PAOO application, averaging 0.18 and 0.17, respectively, compared to 0.05 and 0.07 in the control group. Conclusions The use of PAOO in orthodontic treatment accelerated the leveling and alignment process by 40%. Changes in the inter-canine width, the inter-second-premolar width, and the status of periodontal tissues were minimal and clinically negligible.

Outcome of Colorectal Robotic Surgery in Newly Established Robotic Surgery Center: A Case Series.

INTRODUCTION: The robotic platform compared to laparoscopy has proven to have similar postoperative outcomes, however its adoption in the Middle East has been slow and there is limited data regarding outcomes with its use in small newly established robotic colorectal programs. Our aim was to report our experience and outcomes of robotic colorectal surgery performed by fellowship-trained robotic colorectal surgeons and compare them to larger, more experienced centers. METHODS: This is retrospective review of data collected between November 2021 and March 2023 from a tertiary health care referral center. The series included 51 patients who had elective or urgent robotic colorectal surgery. Patients who had emergency surgery were excluded. The outcomes were overall morbidity, serious morbidity, mortality, conversion to open, length of hospital stay, and quality of oncological specimen. RESULTS: The overall morbidity was 31.4% (n = 16 patients). Only 9.8% (n = 5) had serious morbidity of which three required interventions under general anesthesia. The median length of hospital stay was 6 days (IQR = 4), and there was no mortality. Of 17 rectal cancer resections, 88% had complete mesorectal excision, 15 of them were R0 resections, median lymph node harvested was 14 (IQR = 7) and two cases were converted to open. All the colon cancer resections had R0 resection, median lymph nodes harvested was 21 (IQR = 4) and none were converted to open. CONCLUSIONS: The implementation and integration of robotic colorectal surgery at a newly established center in a small country, when led by fellowship trained robotic colorectal surgeons, is safe and effective in terms of morbidity, mortality, conversion to open and specimen pathological quality.

Deciphering the Enigma of Neuron-Glial Interactions in Neurological Disorders.

Innate lymphocytes, including microglial cells, astrocytes, and oligodendrocytes, play a crucial role in initiating neuroinflammatory reactions inside the central nervous system (CNS). The prime focus of this paper is on the involvement and interplay of neurons and glial cells in neurological disorders such as Alzheimer's Disease (AD), Autism Spectrum Disorder (ASD), epilepsy, and multiple sclerosis (MS). In this review, we explore the specific contributions of microglia and astrocytes and analyzes multiple pathways implicated in neuroinflammation and disturbances in excitatory and inhibitory processes. Firstly, we elucidate the mechanisms through which toxic protein accumulation in AD results in synaptic dysfunction and deregulation of the immune system and examines the roles of microglia, astrocytes, and hereditary factors in the pathogenesis of the disease. Secondly, we focus on ASD and the involvement of glial cells in the development of the nervous system and the formation of connections between neurons and investigates the genetic connections associated with these processes. Lastly, we also address the participation of glial cells in epilepsy and MS, providing insights into their pivotal functions in both conditions. We also tried to give an overview of seven different pathways like toll-like receptor signalling pathway, MyD88-dependent and independent pathway, etc and its relevance in the context with these neurological disorders. In this review, we also explore the role of activated glial cells in AD, ASD, epilepsy, and MS which lead to neuroinflammation. Even we focus on excitatory and inhibitory imbalance in all four neurological disorders as imbalance affect the proper functioning of neuronal circuits. Finally, this review concludes that there is necessity for additional investigation on glial cells and their involvement in neurological illnesses.

The Prevalence of Nephrolithiasis and Associated Risk Factors Among the Population of the Riyadh Province, Saudi Arabia.

Background and objective Kidney stones, also referred to as nephrolithiasis or renal calculi, is a condition where crystal depositions are formed within the kidney and ideally excreted from the body via the urethra with no pain; however, larger calculi may cause significant pain and require further medical assistance. The vast majority of patients who develop renal calculi form calcium stones, which are either a composition of calcium oxalate or calcium phosphate. Other types include uric acid, struvite, and cysteine. While kidney stones are one of the most significant diseases among the Saudi population, which require an acute emergency intervention to prevent serious long-term complications, there are limited studies published regarding this condition in Saudi communities. In light of this, we performed this study to assess the prevalence, incidence, and risk factors of kidney stones among the population of Riyadh, Saudi Arabia. Methods This was a cross-sectional study conducted in Riyadh, Saudi Arabia between August and October 2023, aiming to estimate the prevalence and risk factors of nephrolithiasis among residents of the Riyadh province. Data were collected through an electronic questionnaire in both Arabic and English and distributed via social media in addition to barcode handouts in various selected venues in Riyadh. The questionnaire involved 12 questions categorized into three sections. The first section obtained demographical information while the second section collected data about the past medical history of the participants. Lastly, the third section aimed to assess the prevalence of nephrolithiasis among participants or any history of the condition among their families. Results A total of 1,043 participants were surveyed, of whom 533 were males (51.1%). The prevalence of kidney stones was reported in 98 individuals (9.4%) overall. Individuals in the age groups of 36-50, 51-60, and >60 years showed significantly more renal stone prevalence than those in younger age groups (p<0.001). The prevalence was found to be higher in participants who were smokers, diabetic, hypertensive, and those who suffered from inflammatory bowel disease (IBD), gout, chronic kidney disease (CKD), hyperthyroidism, and hyperparathyroidism. Participants who took calcium supplements or had a positive family history of renal stones were found to have a higher prevalence of renal stones as well. However, only hypertension, gout, and family history showed any statistical significance (p<0.05). Conclusions A direct correlation was observed between hypertension, gout, positive family history, and aging and an increased prevalence of kidney stones among the inhabitants of the Riyadh province. Therefore, we encourage the local authorities to raise awareness of kidney stones and their related risk factors among the general public. Moreover, further local studies need to be conducted to gain deeper insights into kidney stone prevalence, especially pertaining to associated comorbidities and the pattern of the disease itself.

Thorough examination of the potential biological implications of the cuproptosis-related gene LIPT2 in the prognosis and immunotherapy in pan-cancer.

OBJECTIVES: To elucidate the expression levels and prognostic value of the Lipoyltransferase 2 (LIPT2) gene in a pan-cancer view. METHODOLOGY: Our study comprehensively investigated the role of LIPT2 in pan-cancer, combining bioinformatics analyses with experimental validations. RESULTS: Analysis of LIPT2 mRNA expression across various cancers revealed a significant up-regulation in 18 tumor types and down-regulation in 8 types, indicating its diverse involvement. Prognostic assessment demonstrated a correlation between elevated LIPT2 expression and poorer outcomes in Overall Survival (OS) and Disease-Free Survival (DFS), particularly in Glioblastoma Multiforme (GBM), Liver Hepatocellular Carcinoma (LIHC), and Pheochromocytoma and Paraganglioma (PCPG). Protein expression analysis in GBM, LIHC, and PCPG affirmed a consistent increase in LIPT2 levels compared to normal tissues. Examining the methylation status in GBM, LIHC, and PCPG, we found reduced promoter methylation levels in tumor samples, suggesting a potential influence on LIPT2 function. Genetic mutation analysis using cBioPortal indicated a low mutation frequency (< 2%) in LIPT2 across GBM, LIHC, and PCPG. Immune correlation analysis unveiled a positive association between LIPT2 expression and infiltration levels of immune cells in GBM, LIHC, and PCPG. Single-cell analysis illustrated LIPT2's positive correlation with functional states, including angiogenesis and inflammation. Enrichment analysis identified LIPT2-associated processes and pathways, providing insights into its potential molecular mechanisms. Drug sensitivity analysis demonstrated that elevated LIPT2 expression conferred resistance to multiple compounds, while lower expression increased sensitivity. Finally, RT-qPCR validation in HCC cell lines confirmed the heightened expression of LIPT2 compared to a control cell line, reinforcing the bioinformatics findings. CONCLUSION: Overall, our study highlights LIPT2 as a versatile player in cancer, influencing diverse aspects from molecular processes to clinical outcomes across different cancer types.

Pan-cancer analysis of HS6ST2: associations with prognosis, tumor immunity, and drug resistance.

OBJECTIVES: In this comprehensive study spanning 33 malignancies, we explored the differential expression and prognostic significance of Heparan sulfate 6-O-sulfotransferase 2 (HS6ST2). METHODS: TIMER2, UALCAN, and GEPIA2 were used for the expression analysis. cBioPortal was used for mutational analysis. CancerSEA, STRING, and DAVID, were employed for the single cell sequencing data analysis, protein-protein interaction network development, and gene enrichment analyses, respectively. GSCAlite and RT-qPCR were used for drug sensitivity and expression validation analysis. RESULTS: HS6ST2 exhibited significant (P < 0.05) overexpression in multiple cancers. Prognostically, elevated HS6ST2 expression was significantly associated with poor overall survival (OS) in patients with cervical squamous cell carcinoma (CESC), kidney chromophobe (KICH), lung adenocarcinoma (LUAD), and stomach adenocarcinoma (STAD), emphasizing its potential as a prognostic indicator in these cancers. Moreover, HS6ST2 expression correlated with pathological stages in CESC, KICH, LUAD, and STAD patients. Exploration of genetic alterations using cBioPortal unveiled distinct mutational landscapes, with low mutation frequencies in CESC, KICH, LUAD, and STAD. Additionally, reduced DNA methylation in CESC, KICH, LUAD, and STAD suggested a potential link between hypomethylation and heightened HS6ST2 expression. Analysis of immune cell infiltration revealed a positive correlation between HS6ST2 expression and the infiltration of CD8+ T and CD4+ T cells in CESC, KICH, LUAD, and STAD, highlighting its involvement in the tumor immunology processes. Single-cell functional states analysis demonstrated associations between HS6ST2 and diverse cellular processes. Moreover, gene enrichment analysis revealed the involvement HS6ST2 in crucial cellular activities. GSCAlite analysis underscored the potential of HS6ST2 as a therapeutic target, showing associations with drug sensitivity. Finally, experimental validation through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry in LUAD tissues confirmed elevated HS6ST2 expression. CONCLUSION: Overall, this study provides a comprehensive understanding of HS6ST2 in CESC, KICH, LUAD, and STAD, emphasizing its potential as a prognostic biomarker and therapeutic target.

Decoding the DSCC1 gene as a pan-cancer biomarker in human cancers via comprehensive multi-omics analyses.

OBJECTIVES: While dysregulation of DSCC1 (DNA Replication And Sister Chromatid Cohesion 1) has been established in breast cancer and colorectal cancer, its associations with other tumors remain unclear. Therefore, this study was launched to explore the role of DSCC1 in pan-cancer. METHODOLOGY: In this study, we investigate the biological functions of DSCC1 across 33 solid tumors, elucidating its role in promoting oncogenesis and progression in various cancers through comprehensive analysis of multi-omics data. RESULTS: We conducted a comprehensive analysis of DSCC1 expression using RNA-seq data from TCGA and GTEx databases across 30 cancer types. Striking variations were observed, with significant overexpression of DSCC1 identified in numerous cancers. Elevated DSCC1 level was strongly associated with poorer prognosis, shorter survival, and advanced tumor stages in kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), as indicated by Kaplan-Meier curves and GEPIA2 analysis. Further investigation into the molecular mechanisms revealed reduced DNA methylation in the DSCC1 promoter region in KIRP, LIHC, and LUAD, supporting enhanced RNA transcription. Protein expression analysis via the Human Protein Atlas (HPA) corroborated mRNA expression findings, showcasing elevated DSCC1 protein in KIRP, LIHC, and LUAD tissues. Mutational analysis using cBioPortal revealed alterations in 0.4% of KIRP, 17% of LIHC, and 5% of LUAD samples, predominantly characterized by amplification. Immune cell infiltration analysis demonstrated robust positive correlations between DSCC1 expression and CD8+ T cells, CD4+ T cells, and B cells, influencing the tumor microenvironment. STRING and gene enrichment analyses unveiled DSCC1's involvement in critical pathways, emphasizing its multifaceted impact. Notably, drug sensitivity analysis highlighted a significant correlation between DSCC1 mRNA expression and responses to 78 anticancer treatments, suggesting its potential as a predictive biomarker and therapeutic target for KIRP, LIHC, and LUAD. Finally, immunohistochemistry staining of clinical samples validated computational results, confirming elevated DSCC1 protein expression. CONCLUSION: Overall, this study provides comprehensive insights into the pivotal role of DSCC1 in KIRP, LIHC, and LUAD initiation, progression, and therapeutic responsiveness, laying the foundation for further investigations and personalized treatment strategies.

Photonics-powered augmented reality skin electronics for proactive healthcare: multifaceted opportunities.

Rapid technological advancements have created opportunities for new solutions in various industries, including healthcare. One exciting new direction in this field of innovation is the combination of skin-based technologies and augmented reality (AR). These dermatological devices allow for the continuous and non-invasive measurement of vital signs and biomarkers, enabling the real-time diagnosis of anomalies, which have applications in telemedicine, oncology, dermatology, and early diagnostics. Despite its many potential benefits, there is a substantial information vacuum regarding using flexible photonics in conjunction with augmented reality for medical purposes. This review explores the current state of dermal augmented reality and flexible optics in skin-conforming sensing platforms by examining the obstacles faced thus far, including technical hurdles, demanding clinical validation standards, and problems with user acceptance. Our main areas of interest are skills, chiroptical properties, and health platform applications, such as optogenetic pixels, spectroscopic imagers, and optical biosensors. My skin-enhanced spherical dichroism and powerful spherically polarized light enable thorough physical inspection with these augmented reality devices: diabetic tracking, skin cancer diagnosis, and cardiovascular illness: preventative medicine, namely blood pressure screening. We demonstrate how to accomplish early prevention using case studies and emergency detection. Finally, it addresses real-world obstacles that hinder fully realizing these materials' extraordinary potential in advancing proactive and preventative personalized medicine, including technical constraints, clinical validation gaps, and barriers to widespread adoption.

The effect of structural changes on the self-assembly of novel green pyridinium-carboxylate gemini surfactants in Langmuir and Langmuir-Blodgett films.

Engineered molecules with tailored molecular structures have the potential to advance various disciplines by enhancing the properties of biological membranes. In this study, we investigated the fundamental interfacial behavior of newly synthesized, water insoluble, cationic pyridinium-carboxylate based gemini surfactants (GSs) using picolinic acid (PA), nicotinic acid (NA), and isonicotinic acid (INA) and their interactions with dipalmitoylphosphatidylcholine (DPPC) in Langmuir and Langmuir-Blodgett (LB) films. Two synthetic methodologies were employed: (a) connecting two alkyl pyridinecarboxylates through the nitrogen atoms with a xylenyl spacer, namely, PAGS, NAGS1, and INAGS; and (b) dimerizing two nicotinic acid molecules through ester linkages with 1,4-benzenedimethanol, and then quaternizing the pyridine nitrogens with hexadecyl chains to yield NAGS2. A combination of Brewster angle microscopy (BAM) and atomic force microscopy (AFM) imaging techniques yielded valuable insights into the morphology of the GS films and their mixtures with DPPC. Density functional theory (DFT) calculations were used to gain further information on the GSs structures and understand their assembly. The results indicate that the film of INAGS is the most hydrophobic film, and its monolayer is the least compressible. When the nitrogen atom and a carboxylate group of the headgroup are positioned closer to each other, the GS molecules tend to form aggregates instead of a continuous film which is observed for the INAGS surfactant. This observation is consistent with the DFT energy values of pair interactions, indicating that both PAGS and NAGS1 have closely packed conformations with high stabilization energy.

Hesperidin - loaded PVA/alginate hydrogel: targeting NFκB/iNOS/COX-2/TNF-α inflammatory signaling pathway.

Introduction: Skin injuries represent a prevalent form of physical trauma, necessitating effective therapeutic strategies to expedite the wound healing process. Hesperidin, a bioflavonoid naturally occurring in citrus fruits, exhibits a range of pharmacological attributes, including antimicrobial, antioxidant, anti-inflammatory, anticoagulant, and analgesic properties. The main objective of the study was to formulate a hydrogel with the intention of addressing skin conditions, particularly wound healing. Methods: This research introduces a methodology for the fabrication of a membrane composed of a Polyvinyl alcohol - Sodium Alginate (PVA/A) blend, along with the inclusion of an anti-inflammatory agent, Hesperidin (H), which exhibits promising wound healing capabilities. A uniform layer of a homogeneous solution comprising PVA/A was cast. The process of crosslinking and the enhancement of hydrogel characteristics were achieved through the application of gamma irradiation at a dosage of 30 kGy. The membrane was immersed in a Hesperidin (H) solution, facilitating the permeation and absorption of the drug. The resultant system is designed to deliver H in a controlled and sustained manner, which is crucial for promoting efficient wound healing. The obtained PVA/AH hydrogel was evaluated for cytotoxicity, antioxidant and free radical scavenging activities, anti-inflammatory and membrane stability effect. In addition, its action on oxidative stress, and inflammatory markers was evaluated on BJ-1 human normal skin cell line. Results and Discussion: We determined the effect of radical scavenging activity PVA/A (49 %) and PVA/AH (87%), the inhibition of Human red blood cell membrane hemolysis by PVA/AH (81.97 and 84.34 %), hypotonicity (83.68 and 76.48 %) and protein denaturation (83.17 and 85.8 %) as compared to 250 µg/ml diclofenac (Dic.) and aspirin (Asp.), respectively. Furthermore, gene expression analysis revealed an increased expression of genes associated with anti-oxidant and anti-inflammatory properties and downregulated TNFα, NFκB, iNOS, and COX2 by 67, 52, 58 and 60%, respectively, by PVA/AH hydrogel compared to LPS-stimulated BJ-1 cells. The advantages associated with Hesperidin can be ascribed to its antioxidant and anti-inflammatory attributes. The incorporation of Hesperidin into hydrogels offers promise for the development of a novel, secure, and efficient strategy for wound healing. This innovative approach holds potential as a solution for wound healing, capitalizing on the collaborative qualities of PVA/AH and gamma irradiation, which can be combined to establish a drug delivery platform for Hesperidin.

Modified triple pelvic osteotomy for residual acetabular dysplasia through double incisions: Technical note and review of short-term results.

PURPOSE: To assess validity, safety, and efficacy of the modified triple pelvic osteotomy (TPO) approach for correction of residual acetabular dysplasia. METHODS: This is a retrospective case series conducted on 15 hips in 15 patients from 2019 to 2023 with residual acetabular dysplasia treated by modified TPO as described by Tonnis with two modifications. The first modification is using a single medial incision for pubic and ischial cuts (the Vladimirov modification). The second modification is having the ischial cut closer to the acetabulum (Li modification) allowing free movement of the acetabular fragment for better femoral head coverage. The mean age at the time of surgery was 11.85 years, (range 8-23). Cases presenting were 10 males (66.7%) and 5 females (33.3%). The mean follow-up period was 36.533 months (24-60 months). RESULTS: Our study revealed significant clinical and radiological improvement. The CE angle improved from a mean value of 10° (range 2-17) pre-operatively to 32.785° (range 18°-40°) post-operatively. The AI improved from a mean value of 32° pre-operatively to a mean value of 13.89° post-operatively. HHS increased from a preoperative mean value of 74.80° to a post-operative mean value of 90.67°. Also, there was a significant improvement in ROM (abduction and internal rotation). LLD improved from a mean value of 2.60 cm preoperatively to a mean value of 0.37 cm postoperatively. Delayed union was found in 3 cases. No cases of osteonecrosis or neurovascular complication were encountered in our study. CONCLUSION: The modified TPO technique using dual incisions can be considered safe and effective, providing adequate coverage of the femoral head in acetabular dysplasia with less surgical time, satisfactory functional outcomes, and minimal complications. LEVEL OF EVIDENCE: IV.

Periodontitis and Inflammatory Bowel Disease: A Review.

The complex relationship between periodontitis (PD) and inflammatory bowel disease (IBD) has received significant attention in recent studies. Emerging evidence suggests that the oral-gut axis plays a pivotal role in their interaction. This review provides a comprehensive, up-to-date analysis of original research from 2003 to 2023 on the PD-IBD relationship and aims to be a reference for future research. Relevant literature was sourced from the PubMed database using the keywords "periodontitis" and "inflammatory bowel disease". Additionally, a manual library search and a review of bibliographies were conducted. Of the 297 articles retrieved, 27 studies were chosen for final review. Out of these, 21 studies (78%), including both in vitro and in vivo research, indicated an association between PD and IBD. While many studies confirm a bi-directional relationship, others refute it or deem it clinically irrelevant. There is a need for more accessible studies, such as randomized trials, which also investigate the factors that could influence the outcomes to clarify the exact molecular mechanisms and clinical implications of this complex relationship.

CDCA8, a mitosis-related gene, as a prospective pan-cancer biomarker: implications for survival prognosis and oncogenic immunology.

BACKGROUND: Human cell division cycle-associated protein 8 (CDCA8), a critical regulator of mitosis, has been identified as a prospective prognostic biomarker in several cancer types, including breast, colon, and lung cancers. This study analyzed the diagnostic/prognostic potential and clinical implications of CDCA8 across diverse cancers. METHODS: Bioinformatics and molecular experiments. RESULTS: Analyzing TCGA data via TIMER2 and GEPIA2 databases revealed significant up-regulation of CDCA8 in 23 cancer types compared to normal tissues. Prognostically, elevated CDCA8 expression correlated with poorer overall survival in KIRC, LUAD, and SKCM, emphasizing its potential as a prognostic marker. UALCAN analysis demonstrated CDCA8 up-regulation based on clinical variables, such as cancer stage, race, and gender, in these cancers. Epigenetic exploration indicated reduced CDCA8 promoter methylation levels in Kidney Renal Clear Cell Carcinoma (KIRC), Lung Adenocarcinoma (LUAD), and Skin Cutaneous Melanoma (SKCM) tissues compared to normal controls. Promoter methylation and mutational analyses showcased a hypomethylation and low mutation rate for CDCA8 in these cancers. Correlation analysis revealed positive associations between CDCA8 expression and infiltrating immune cells, particularly CD8+ and CD4+ T cells. Protein-protein interaction (PPI) network analysis unveiled key interacting proteins, while gene enrichment analysis highlighted their involvement in crucial cellular processes and pathways. Additionally, exploration of CDCA8-associated drugs through DrugBank presented potential therapeutic options for KIRC, LUAD, and SKCM. In vitro validation using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) confirmed elevated CDCA8 expression in LUAD cell lines (A549 and H1299) compared to control cell lines (Beas-2B and NL-20). CONCLUSION: This study provides concise insights into CDCA8's multifaceted role in KIRC, LUAD, and SKCM, covering expression patterns, diagnostic and prognostic relevance, epigenetic regulation, mutational landscape, immune infiltration, and therapeutic implications.