Twist2 amplification in rhabdomyosarcoma represses myogenesis and promotes oncogenesis by redirecting MyoD DNA binding.

Rhabdomyosarcoma (RMS) is an aggressive pediatric cancer composed of myoblast-like cells. Recently, we discovered a unique muscle progenitor marked by the expression of the Twist2 transcription factor. Genomic analyses of 258 RMS patient tumors uncovered prevalent copy number amplification events and increased expression of TWIST2 in fusion-negative RMS. Knockdown of TWIST2 in RMS cells results in up-regulation of MYOGENIN and a decrease in proliferation, implicating TWIST2 as an oncogene in RMS. Through an inducible Twist2 expression system, we identified Twist2 as a reversible inhibitor of myogenic differentiation with the remarkable ability to promote myotube dedifferentiation in vitro. Integrated analysis of genome-wide ChIP-seq and RNA-seq data revealed the first dynamic chromatin and transcriptional landscape of Twist2 binding during myogenic differentiation. During differentiation, Twist2 competes with MyoD at shared DNA motifs to direct global gene transcription and repression of the myogenic program. Additionally, Twist2 shapes the epigenetic landscape to drive chromatin opening at oncogenic loci and chromatin closing at myogenic loci. These epigenetic changes redirect MyoD binding from myogenic genes toward oncogenic, metabolic, and growth genes. Our study reveals the dynamic interplay between two opposing transcriptional regulators that control the fate of RMS and provides insight into the molecular etiology of this aggressive form of cancer.

Antimicrobial Activity of Gallium(III) Compounds: Pathogen-Dependent Targeting of Multiple Iron/Heme-Dependent Biological Processes.

Metals play vital roles in biological systems, with iron/heme being essential for cellular and metabolic functions necessary for survival and/or virulence in many bacterial pathogens. Given the rise of bacterial resistance to current antibiotics, there is an urgent need for the development of non-toxic and novel antibiotics that do not contribute to resistance to other antibiotics. Gallium, which mimics iron, has emerged as a promising antimicrobial agent, offering a novel approach to combat bacterial infections. Gallium does not have any known functions in biological systems. Gallium exerts its effects primarily by replacing iron in redox enzymes, effectively inhibiting bacterial growth by targeting multiple iron/heme-dependent biological processes and suppressing the development of drug resistance. The aim of this review is to highlight recent findings on the mechanisms of action of gallium and provide further insights into the development of gallium-based compounds. Understanding the mechanisms underlying gallium's biological activities is crucial for designing drugs that enhance their therapeutic therapies while minimizing side effects, offering promising avenues for the treatment of infectious diseases.

Investigating NanoLuc-EGFR engineered cell lines for real-time monitoring of EGFR protein dynamics in live cells.

Evaluating the steady-state protein level of the EGFR in live cells presents significant challenges compared to measuring its kinase activity. Traditional testing methods, such as immunoblotting, ELISA, and immunofluorescence assays, are generally restricted to fixed cells or cell lysates. Despite their utility, these methods are cumbersome and provide only intermittent snapshots of EGFR levels at specific time points. With emerging trends in drug development shifting toward engineering novel agents that promote protein degradation, rather than simply inhibiting kinase activity, a tool that enables real-time, quantitative detection of drug effects in live cells could catalyze advances in the field. Such an innovation would expedite the drug development process, enhancing the translation of research findings into effective, patient-centered therapies. The NanoLuc-EGFR cell line, created through CRISPR genome editing, allows for the continuous tracking and analysis of EGFR protein levels and their degradation within live cells. This approach provides quantitative monitoring of protein dynamics in real time, offering insights that go beyond absolute protein levels to include aspects such as protein stability and degradation rate. Using this cell line model, we observed that AT13387 and H84T BanLec induce EGFR degradation in A549-HiBiT cells, with the results confirmed by immunoblotting. In contrast, Erlotinib, Osimertinib, and Cetuximab inhibit EGFR phosphorylation without altering total EGFR levels, as validated by the HiBiT luciferase assay. The NanoLuc-EGFR cell line marks a significant advancement in understanding protein regulation and serves as an instrumental platform for investigating targeted therapies that modulate protein kinases, especially those that induce protein degradation.

Dysregulated Apoptosis and Autophagy in Childhood Epilepsy: Correlation to Clinical and Pharmacological Patterns.

OBJECTIVES: We aimed to assess the serum levels of caspase-3 as a marker of apoptosis and microtubule-associated protein 1A/1B-light chain 3 (MAP1-LC3) as an autophagy marker in epileptic children with various clinical and pharmacological types. METHODS: This case-control study was carried out on 90 participants (50 pediatric patients with epilepsy and 40 healthy matched children), the patients were categorized into three groups: Group (A): 25 pharmacosensitive epilepsy, Group (B): 25 pharmacoresistant epilepsy, and Group (C): 40 (age, sex, and body mass index) matched healthy children selected as controls. Serum caspase-3 and MAP1-LC3 were measured in all study groups, using commercially available ELISA kits. RESULTS: Serum caspase-3 was significantly higher among epileptic children, especially in the pharmacoresistant group, cases managed with multiple antiepileptic drugs, and cases with abnormal EEG findings. Conversely, circulating MAP1-LC3 levels showed a significant reduction in epilepsy cases, particularly in pharmacoresistant cases, in cases treated with multiple antiepileptic drugs, and in cases with abnormal EEG data. A significant negative correlation between serum caspase-3 and MAP1-LC3 was found among epileptic children (r = -0.369, p = 0.0083). Serum caspase-3 was a more valid biomarker in helping diagnose childhood epilepsy, while serum MAP1-LC3 was more valid in predicting pharmacoresistant type. CONCLUSION: The study reveals that serum caspase-3 levels were significantly elevated, particularly in pharmacoresistant cases and those managed with multiple drugs. Conversely, MAP1-LC3 levels were significantly reduced in epilepsy cases, suggesting potential involvement of altered apoptosis and autophagy in childhood epilepsy.

Clinical and biochemical assessments of circulating High Mobility Group Box Protein1 in children with epilepsy: relation to cognitive function and drug responsiveness.

BACKGROUND: Childhood epilepsy is a major health concern posing a significant burden and having disastrous consequences for cognitive function. High Mobility Group Box1 (HMGB1) is an activator of neuroinflammation, and it is possibly involved in the initiation and progression of epilepsy. We aimed to investigate circulating HMGB1 in children with epilepsy and its connection to cognitive function and drug responsiveness. METHODS: Case-control research included 100 epileptic youngsters and 100 healthy matched controls. Serum HMGB1 was measured using a commercially available ELISA assay. Cognitive functions were evaluated by the Stanford-Binet test 5th edition. RESULTS: Drug-resistant epilepsy (DRE) was found in 37% of the investigated patients. Epileptic children have lower cognitive function parameter levels versus the control group and lower cognitive function in the DRE group compared to the drug-responsive group (P-value < 0.0001). HMGB1 levels were significantly higher in the patients' group (6.279 µg/L) compared to the control group (2.093 µg/L) and in the drug-resistant group (14.26 µg/L) versus the drug-responsive group (4.88 µg/L). A significant negative correlation was detected between HMGB1 with Full-scale IQ (r = - 0.547, P = 0.000), Visual-spatial reasoning (r = - 0.501, P = 0.000), fluid reasoning (r = - 0.510, P = 0.000), and working memory (r = - 0.555, P = 0.000). Serum HMGB1 cut-off levels > 6.85 µg/L differentiate drug-responsive from resistant patients. CONCLUSION: Elevated HMGB1 levels, especially in patients with drug-resistant epilepsy, correlate negatively with cognitive performance, emphasizing its importance as a potential marker for early prediction of drug resistance and impairment of cognitive function.

Effect of Adding Integrated Core and Graduated Upper Limb Exercises to Inpatient Cardiac Rehabilitation on Sternal Instability After Coronary Artery Bypass Grafting: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of adding integrated core and graduated resistance upper limb exercises to an inpatient cardiac rehabilitation program in patients with acute sternal instability after coronary artery bypass grafting (CABG). DESIGN: This was a single-center, randomized, controlled, parallel-group intervention study. SETTING: This study was conducted at the National Heart Institute. PARTICIPANTS: Forty patients with post-CABG with sternal instability aged 50-60 years completed this study and were randomized into 2 groups: an intervention group (n=20) and an active control group (n=20). INTERVENTION: The intervention group (A) received a routine inpatient rehabilitation program from the first postoperative day plus integrated core and graduated resistance upper limb exercises, which started from the seventh postoperative day for approximately 4 weeks, whereas the control group (B) received only the routine inpatient rehabilitation program. MAIN OUTCOME MEASURES: Sternal separation measured by ultrasonography, visual analog scale for measuring pain, and activities of daily living (ADL) index were main outcome measures. RESULTS: Patients in the intervention group (A) showed a significant reduction in sternal separation from the supine and long sitting positions, whereas those in the control group (B) showed a significant increase in sternal separation (P=.0001). Both groups showed a reduction in pain, and an increase in the ADL score was observed in group A. There was a significant interaction between the time and group effects (P=.0001). CONCLUSION: Adding integrated core and graduated upper limb exercises to inpatient cardiac rehabilitation for patients with sternal instability after coronary artery bypass grafting significantly improved sternal healing, pain, and ADL.

In Vitro and In Vivo Preventive Effects of Thymoquinone against Breast Cancer: Role of DNMT1.

Breast cancer (BC) is one of the most common cancers in women and is a major cause of female cancer-related deaths. BC is a multifactorial disease caused by the dysregulation of many genes, raising the need to find novel drugs that function by targeting several signaling pathways. The antitumoral drug thymoquinone (TQ), found in black seed oil, has multitargeting properties against several signaling pathways. This study evaluated the inhibitory effects of TQ on the MCF7 and T47D human breast cancer cell lines and its antitumor activity against BC induced by a single oral dose (65 mg/kg) of 7,12-dimethylbenzanthracene (DMBA) in female rats. The therapeutic activity was evaluated in DMBA-treated rats who received oral TQ (50 mg/kg) three times weekly. TQ-treated MCF7 and T47D cells showed concentration-dependent inhibition of cell proliferation and induction of apoptosis. TQ also decreased the expression of DNA methyltransferase 1 (DNMT1) in both cancer cell types. In DMBA-treated animals, TQ inhibited the number of liver and kidney metastases. These effects were associated with a reduction in DNMT1 mRNA expression. These results indicate that TQ has protective effects against breast carcinogens through epigenetic mechanisms involving DNMT1 inhibition.

A closer look: obsessive-compulsive symptoms among intern nurses amidst COVID-19 pandemic.

BACKGROUND: The distinctive circumstances and socio-cultural context in Egypt make it crucial to explore the psychological well-being of intern nurses amid the COVID-19 pandemic, with a specific focus on obsessive-compulsive symptoms. This study aimed to investigate the influence of fear of COVID-19 on obsessive-compulsive symptoms among intern nurses. METHODS: A cross-sectional survey involving 375 randomly recruited intern nurses was conducted. Data collected included the Fear of COVID-19 Scale and the Short Version of the Arabic Obsessive-Compulsive Scale. RESULTS: A significant relationship was found between the fear of COVID-19 and the severity of obsessive-compulsive symptoms among the participants (r = 0.472, p = 0.000). A stepwise regression analysis indicated that the fear of COVID-19, living in urban regions, frequency of COVID-19 infection, and increased number of infected family members may contribute to the severity of Obsessive-Compulsive Symptoms with adjusted R2 value = 27.5%. CONCLUSION: The findings suggest that the COVID-19 pandemic has had significant psychological impacts on newly qualified nurses during their internship training period, including the manifestation of mental health symptoms such as Obsessive-Compulsive Symptoms. It was observed that urban residents, intern nurses with recurrent COVID-19 infections, and those with more infected family members exhibited a higher severity of OCS. These findings underscore the need for further research to investigate additional factors that may influence OCS severity.

Cluttered spaces, strained bonds: Examining the correlation between hoarding symptoms and social functioning among long-term care facilities older adult residents.

BACKGROUND: Symptoms of hoarding, such as the inability to part with possessions, leading to significant clutter, are commonly observed among residents in long-term care facilities in Egypt. This behavior significantly impacts their social interactions and functioning. Therefore, this study examined the relationship between hoarding symptoms and social functioning among older adult residents in long-term care facilities. METHODS: The study employed a cross-sectional survey on a purposive sample of 300 older adults. TOOLS: Saving Inventory-Revised and Functional Idiographic Assessment Template-Questionnaire-Short Form were used. RESULTS: The findings revealed a significant positive correlation between hoarding symptoms and social functioning (r = 0.682, p < 0.000). A linear regression analysis supported this correlation, establishing hoarding symptoms as a significant predictor of social functioning (adjusted R2 = 0.32). CONCLUSION: The current study highlighted that a significant proportion of long-term care older adult residents displayed moderate hoarding symptoms and compromised social functioning. A noticeable positive association was observed between hoarding symptoms and social functioning. These results underscore the potential impact of hoarding symptoms on various aspects of social functioning. Given these findings, long-term care nurses should comprehend the various facets of compulsive hoarding behavior and devise effective strategies for assessment and intervention. Establishing support groups within these facilities could provide a platform for these residents to share their experiences and coping strategies. This could reduce interpersonal conflicts and argumentativeness and foster emotional expression and intimacy.

Risk perceptions and preventive preparedness toward anthrax re-emergence within the lens of one health in Northcentral Nigeria.

Anthrax has re-emerged in domestic ruminants in Nigeria with public health concerns. This study assessed stakeholders' perceptions and preventive preparedness toward further resurgence and spread at the human-animal-environment interface. A questionnaire-based cross-sectional study was conducted in Nigeria. Descriptive and analytical statistical analyses were performed at 95% confidence levels. All the 384 recruited stakeholders responded. The majority (96.2%) of animal health practitioners (AHPs) and 56.7% of pastoralists were aware of the recent anthrax re-emergence in Nigeria (p < 0.001). Noteworthy, 88.5% of the AHPs and 32.2% of pastoralists mentioned that anthrax has an environmental component in its transmission to humans and animals. From the environmental perspective, 87.7% of AHPs and 24.0% of pastoralists significantly perceived that soil and aerosol contamination with anthrax spores are highly plausible explanation routes for its re-emergence. Extreme weather events (high rainfall, flooding, winds, and drought) (p = 0.001); grazing of livestock on pastures grown on contaminated soil (p < 0.001), transboundary movement and trade of animals (p = 0.001); introduction of new animals into the herds without quarantine (p = 0.001); and bioterrorism (p < 0.001) were more likely to influence the re-emergence and spread of anthrax. To tackle gaps in knowledge and risk perceptions, and address the socio-economic and anthropogenic drivers, cooperation and collaborations through the lens of the One Health approach are needed. The partnership will promote an integrated disease surveillance system from planning to implementation for the realization of elimination or reduction of the burden of anthrax and other zoonoses in Nigeria and contribute to achieving food safety, food security, and public and ecosystem health.

Biochemical and Pharmacological Assessments of Tramadol Abuse on Human Male Fertility: Relation to Seminal Plasma 8-Hydroxyguanosine and Zinc.

Tramadol is a pain killing drug highly used worldwide. There is a knowledge gap for fertility consequences of analgesic addiction in men. In this observational study, we investigated the hazards of tramadol abuse on human male reproductive function. A total of 30 tramadol addicts and 30 healthy controls have participated in the study. History and clinical examination of the included subjects were performed. Biochemical and molecular assays were measured in all participants include serum reproductive hormones (calculated free testosterone, FSH, LH, prolactin and estradiol) using ELISA techniques, semen analysis, seminal plasma zinc and selenium assays using colorimetric kits, seminal plasma tramadol concentrations using Gas Chromatography-Mass Spectrometry (GC-MS), and seminal plasma 8-hydroxyguanosine (8-OHG) using high performance liquid chromatography were measured. Tramadol abuse significantly decreased semen parameters quality. Additionally, tramadol abuse significantly decreased testosterone (P = 0.001) and increased prolactin serum levels (P = 0.000). Tramadol abusers showed significantly higher levels of 8-OHG (P < 0.0001) with significantly lower levels of zinc and selenium in their seminal plasma compared with the controls (P < 0.0001, and 0.0002 respectively). Also, tramadol addicts displayed positive correlations between seminal plasma levels of 8-OHG (r = 0.905, P = 0.00) and sperm abnormal forms (r = 0.610, P = 0.000) with seminal plasma tramadol levels. Seminal plasma levels of zinc (r = - 0.815, P = 0.00), sperm motility (r = - 0.484, P = 0.007), and vitality (r = - 0.430, P = 0.018) were negatively correlated with seminal plasma levels of tramadol. Our data suggest that tramadol abuse may impair male fertility by increasing oxidative damage of sperms and reducing testosterone and the antioxidants trace elements in testicular tissues. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-023-01141-4.

NOTCH-YAP1/TEAD-DNMT1 Axis Drives Hepatocyte Reprogramming Into Intrahepatic Cholangiocarcinoma.

BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (ICC) is a devastating liver cancer with extremely high intra- and inter-tumoral molecular heterogeneity, partly due to its diverse cellular origins. We investigated clinical relevance and the molecular mechanisms underlying hepatocyte (HC)-driven ICC development. METHODS: Expression of ICC driver genes in human diseased livers at risk for ICC development were examined. The sleeping beauty and hydrodynamic tail vein injection based Akt-NICD/YAP1 ICC model was used to investigate pathogenetic roles of SRY-box transcription factor 9 (SOX9) and yes-associated protein 1 (YAP1) in HC-driven ICC. We identified DNA methyltransferase 1 (DNMT1) as a YAP1 target, which was validated by loss- and gain-of-function studies, and its mechanism addressed by chromatin immunoprecipitation sequencing. RESULTS: Co-expression of AKT and Notch intracellular domain (NICD)/YAP1 in HC yielded ICC that represents 13% to 29% of clinical ICC. NICD independently regulates SOX9 and YAP1 and deletion of either, significantly delays ICC development. Yap1 or TEAD inhibition, but not Sox9 deletion, impairs HC-to-biliary epithelial cell (BEC) reprogramming. DNMT1 was discovered as a novel downstream effector of YAP1-TEAD complex that directs HC-to-BEC/ICC fate switch through the repression of HC-specific genes regulated by master regulators for HC differentiation, including hepatocyte nuclear factor 4 alpha, hepatocyte nuclear factor 1 alpha, and CCAAT/enhancer-binding protein alpha/beta. DNMT1 loss prevented NOTCH/YAP1-dependent HC-driven cholangiocarcinogenesis, and DNMT1 re-expression restored ICC development following TEAD repression. Co-expression of DNMT1 with AKT was sufficient to induce tumor development including ICC. DNMT1 was detected in a subset of HCs and dysplastic BECs in cholestatic human livers prone to ICC development. CONCLUSION: We identified a novel NOTCH-YAP1/TEAD-DNMT1 axis essential for HC-to-BEC/ICC conversion, which may be relevant in cholestasis-to-ICC pathogenesis in the clinic.

A prospective study on disorders of sex development in Duhok city, Kurdistan region, Iraq: Genetic, etiology and clinical presentation.

Disorders of Sexual Development (DSD) encompass all types of intersex cases and have been reported globally. However, in Iraq, studies related to DSD are scanty.  The current single-center prospective study was carried out to find out the frequency, genetic and clinical presentation of different types of DSDs in the sample population of Duhok, Iraq. The sample comprises 40 DSD patients who have been referred to Hivi Pediatric Teaching Hospital in Duhok, Kurdistan region, Iraq, from June 2017 to June 2022. We conducted karyotype-based classification, laparoscopic-based internal organ diagnosis and abdominal ultrasound to diagnose DSDs in the target population. Of the total 40 cases, 19 (47.5%) were males, and 21 (52.5%) were females. Among them, 85 % were diagnosed as peno- scrotal hypospadias, 10% had clitoromegaly and the remaining were diagnosed as under-developed female-like genitalia. The majority of the patients were diagnosed with congenital adrenal hyperplasia (CAH) (55%), 37.5% were Testicular Feminization Syndrome (TFS) and the remaining were rare categories that we did not reach final diagnosis. Laparoscopy was done for 77.5 % of the participants of whom 30% had small uterus and ovaries, 25% had Intra-abdominal testes and the remaining had testes &ovaries, Mullerian Inhibitory Factor (MIF) deficiency and TFS. The study found different types of DSDs in the target population that requires both physical and psychological intervention. Future studies should focus on evaluating DSDs in larger populations and at multi-centers to understand the condition's trajectory in the Iraqi population.

Validity of Serum Zinc/Copper Ratio as a Potential Novel Biomarker in Childhood Epilepsy.

BACKGROUND: Alterations in zinc and copper homeostasis may contribute to seizure susceptibility, development, termination, and response to antiepileptic medications. The current study examined the profile of zinc, copper, and their ratio in childhood epilepsy and its pharmacological variants (pharmacoresistant and pharmacoresponsive). METHODS: The study included 100 epileptic children (50 pharmacoresistant and 50 pharmacoresponsive) and 50 healthy, age- and gender-matched controls. History, clinical examination, and assays of serum zinc and copper were performed. Zinc/copper ratio was calculated. RESULTS: Serum zinc and the zinc/copper ratio were significantly lower in epileptic children than in controls (p < 0.001). Significantly lower zinc and zinc/copper ratio and higher copper levels were found in children treated with levetiracetam/sodium valproate/oxcarbazepine than those treated with levetiracetam alone or combined with sodium valproate (p < 0.05 for all). Epileptic children, particularly pharmacoresistant, exhibited significant negative correlations between the serum levels of zinc and copper (r = -0.279, p = 0.005, and r = -0.363 and p = 0.010, respectively). At cutoff value of zinc/copper ratio < 1.118 in diagnosing children with epilepsy, it gives a sensitivity of 64% and a specificity of 85% with the AUC = 0.8092. At cutoff value of zinc/copper ratio ≤ 0.7826 in distinguishing pharmacoresistant epilepsy, it produced 52% sensitivity, 64% specificity with AUC = 0.576 Conclusions: Low zinc and high copper levels were associated with childhood epilepsy especially those with pharmacoresistant type and treated with Oxcarbazepine. Zinc/copper ratio might be a potential biomarker in diagnosing childhood epilepsy and to some extent in predicting pharmacoresistant type.

The use of Traditional Medicines for Sexual Enhancement in Northern Nigeria.

BACKGROUND: There is a paucity of information on the use of traditional medicine TM to improve sexual performance. This study aims to assess the prevalence and self-reported adverse effects associated with the use of TM as a sexual enhancer in northern Nigeria. METHODS: The study was a cross-sectional design among adults aged 18 years and above, who are residing in northern Nigeria. A mixed-mode approach was utilized using face-to-face interviews and an online survey. For the online survey, a link to the questionnaire was shared on the social media platforms of the targeted participants. RESULTS: A total of 794 eligible participants completed the survey over the six weeks. Of this number, 508 reported ever using TM for sexual enhancement, with a prevalence of 64% (95% CI: 60.5, 67.3). About 30 (3.8%) reported daily use, 49 (4.9%) weekly, 65 (8.2%) monthly and 473 (59.6%) as when needed. Islamic medicine was the most frequently implicated TM. Most respondents obtained it TM practitioners 213 (26.8%). Participants 164 (20.7%) reported experiencing side effects, mostly headaches 59 (35.9%), and 31 (3.9%) were severe (required hospitalization). Predictors of TM use for sexual enhancement were found to be gender, marital status, number of wives, ethnicity, educational level, and lifestyle. CONCLUSION: The use of TM for sexual enhancement is common among the adult population in northern Nigeria. One out of five of the users reported an adverse event. Therefore, there is a need for improved awareness of the safe use of the TM in the community, especially among females, those with multiple wives, a low education level, and poor lifestyles.

Profile of plasma free amino acids, carnitine and acylcarnitines, and JAK2v617f mutation as potential metabolic markers in children with type 1 diabetic nephropathy.

Fifty diabetic nephropathy (DN) children with type 1 diabetes mellitus (T1DM) and 50 healthy matched controls were included. Chromatographic assays of 14 amino acids, free carnitine and 27 carnitine esters using high-performance liquid chromatography/electrospray ionization-mass spectroscopy, and genetic testing for JAK2v617f mutation using real-time PCR were performed. Patients had significantly lower levels of tyrosine, branched-chain amino acids (BCAAs), and BCAA/AAA (aromatic chain amino acids) ratios, glycine, arginine, ornithine, free carnitine and some carnitine esters (C5, 6, 12 and 16) and higher phenylalanine, phenylalanine/tyrosine ratio and C18 compared with the controls and in the macro-albuminuria vs. the microalbuminuria group (p < 0.05 for all) except for free carnitine. Plasma carnitine was negatively correlated with eGFR (r = -0.488, p = 0.000). There were significant positive correlations between tyrosine with UACR ratio (r = 0.296, p = 0.037). The plasma BCAA/AAA ratio showed significant negative correlations with UACR (r = -0.484, p = 0.000). There was a significantly higher frequency of the JAK2V617F gene mutation in diabetic nephropathy patients compared with the control group and in macro-albuminuria than the microalbuminuria group (p = 0.000) for both. When monitoring children with T1DM, plasma free amino acids and acylcarnitine profiles should be considered, especially if they have tested positive for JAK2V617F for the early diagnosis of DN.

The use of Husserl's phenomenology in nursing research: A discussion paper.

AIMS: To discuss how Husserl's descriptive phenomenology, as a philosophy and approach, has been used and reported in researching the experiences of others, using the topic of foreign-trained nurses. DESIGN: Discussion paper. DATA SOURCES: A systematic search of MEDLINE (PubMed), CINAHL, SCOPUS, British Nursing Database and PsycInfo was carried out in December 2021. The inclusion criteria were peer-reviewed phenomenological research articles, grounded by Husserl's philosophy, conducted among foreign-trained nurses and published in English from 2000 to 2021. FINDINGS: Two main themes were the outcome of critically reviewing relevant selected literature, 'referring to the original philosophy is not enough' and 'phenomenological findings need to be phenomenological'. These findings confirm some arguments about nurse researchers' discrepant use of phenomenology in their studies, including the proper application of phenomenological notions on the ground. IMPLICATION FOR NURSING: Nurse researchers need to clearly distinguish between phenomenology and other qualitative research approaches and consider the uniqueness of philosophical underpinnings that are essential in Husserl's phenomenology, which also need to be clearly applied and reflected in their studies. CONCLUSION: There are continually existing discrepancies and variations in using phenomenology by nurse researchers. These variations were uniquely evident when nurse researchers could not provide enough philosophical grounds and assumptions to their studies and underestimated the need to keep up with the various applications of Husserl's phenomenological notions, including the proper practice of phenomenological attitude. Therefore, it is recommended that nurse researchers should opt for different, less complex qualitative approaches if they do not adequately prepare and understand what constitutes phenomenology and the particulars of Husserl's philosophy. IMPACT: What problem did the study address? Phenomenology remains popular in nursing. However, it can confuse nurse researchers and may result in an improper understanding of its core concepts. The use of phenomenology in nursing has been criticized over the years with nurse researchers being accused of conducting phenomenological research inconsistent with the original philosophy. What were the main findings? Using phenomenology by nurse researchers is various and includes some discrepancies. This variation is caused by not complying with essential philosophical grounds and underestimating proper applications of Husserl's phenomenological notions. Where and on whom will the research have impact? Outcomes of this paper illustrate examples of proper and improper uses of Husserl's phenomenology in nursing research, including critical considerations, which can guide nurse researchers aiming to conduct descriptive phenomenological research. Additionally, nurse lecturers can utilize this paper to show and emphasize the importance of philosophical grounds in phenomenology. NO PATIENT OR PUBLIC CONTRIBUTION: Due to the nature of this discussion paper addressing philosophical and methodological aspects using examples from the literature, no direct patient or public contribution was required.

Evaluation of enamel wear by 3 occlusal splint materials: An in vitro study.

STATEMENT OF PROBLEM: Occlusal devices used to manage bruxism have been commonly fabricated from polymethyl methacrylate with the powder-liquid technique. More recently, Vertex ThermoSens (VTS) and the biocompatible high-performance polymer (BioHPP), an optimized material having polyetheretherketone (PEEK) as its basis, have been used, but little is known about the wear of these materials on human enamel. PURPOSE: The purpose of this in vitro study was to assess via a mastication simulation test how 3 occlusal device materials affected the wear and roughness of enamel antagonists. MATERIAL AND METHODS: A noncontact 3D optical profilometer was used to measure the enamel surface roughness (Ra) against 3 occlusal device materials: vertex regular, VTS, and PEEK high-performance polymer (BioHPP). A dual-axis mastication simulator was used to perform a 2-body wear test on specimens from each group. The test consisted of 10 000 cycles with a 70-N force and 5 to 55 °C thermocycling. Following simulated mastication, the weight of each specimen and the Ra change were compared with the Kolmogorov-Smirnov test, paired specimens t test, Wilcoxon signed-rank test, and 1-way analysis of variance (α=.05). RESULTS: The polyamide group caused the lowest amount of enamel wear (P<.05), while the heat-polymerized acrylic resin group induced the largest amount of enamel wear (P<.05). For polyamide and PEEK, the change in enamel surface roughness exhibited a smooth texture, whereas it found a rougher surface for the heat-polymerized acrylic resin. CONCLUSIONS: According to this study, surface roughness and wear on human enamel were not correlated. PEEK is a promising material for the fabrication of occlusal devices.

Molecular Docking of Bacterial Protein Modulators and Pharmacotherapeutics of Carica papaya Leaves as a Promising Therapy for Sepsis: Synchronising In Silico and In Vitro Studies.

Sepsis is a serious health concern globally, which necessitates understanding the root cause of infection for the prevention of proliferation inside the host's body. Phytochemicals present in plants exhibit antibacterial and anti-proliferative properties stipulated for sepsis treatment. The aim of the study was to determine the potential role of Carica papaya leaf extract for sepsis treatment in silico and in vitro. We selected two phytochemical compounds, carpaine and quercetin, and docked them with bacterial proteins, heat shock protein (PDB ID: 4PO2), surfactant protein D (PDB ID: 1PW9), and lactobacillus bacterial protein (PDB ID: 4MKS) against imipenem and cyclophosphamide. Quercetin showed the strongest interaction with 1PW9 and 4MKS proteins. The leaves were extracted using ethanol, methanol, and water through Soxhlet extraction. Total flavonoid content, DPPH assay, HPTLC, and FTIR were performed. In vitro cytotoxicity of ethanol extract was screened via MTT assay on the J774 cell line. Ethanol extract (EE) possessed the maximum number of phytocomponents, the highest amount of flavonoid content, and the maximum antioxidant activity compared to other extracts. FTIR analysis confirmed the presence of N-H, O-H, C-H, C=O, C=C, and C-Cl functional groups in ethanol extract. Cell viability was highest (100%) at 25 µg/mL of EE. The present study demonstrated that the papaya leaves possessed antibacterial and cytotoxic activity against sepsis infection.

Harnessing Artificial Intelligence: Strategies for Mental Health Nurses in Optimizing Psychiatric Patient Care.

This narrative review explores the transformative impact of Artificial Intelligence (AI) on mental health nursing, particularly in enhancing psychiatric patient care. AI technologies present new strategies for early detection, risk assessment, and improving treatment adherence in mental health. They also facilitate remote patient monitoring, bridge geographical gaps, and support clinical decision-making. The evolution of virtual mental health assistants and AI-enhanced therapeutic interventions are also discussed. These technological advancements reshape the nurse-patient interactions while ensuring personalized, efficient, and high-quality care. The review also addresses AI's ethical and responsible use in mental health nursing, emphasizing patient privacy, data security, and the balance between human interaction and AI tools. As AI applications in mental health care continue to evolve, this review encourages continued innovation while advocating for responsible implementation, thereby optimally leveraging the potential of AI in mental health nursing.