Evaluation of the expression of fibrosis-related genes as non-invasive diagnostic biomarkers for cirrhotic HCV-infected patients.

Liver cirrhosis is a condition with high mortality that poses a significant health and economic burden worldwide. The clinical characteristics of liver cirrhosis are complex and varied. Therefore, the evaluation of immune infiltration-involved genes incirrhosis has become mandatory in liver disease research, not only to identify the potential biomarkers but also to provide important insights into the underlying mechanisms of the disease. In this study, we aimed to investigate the expression profile of cytokine genes in peripheral blood mononuclear cells (PBMCs) of HCV patients and identify the gene expression signature associated with advanced cirrhosis. A cross-sectional study of 90 HCV genotype 4 patients, including no fibrosis patients (F0, n = 24), fibrotic patients (F1-F3, n = 36), and cirrhotic patients (F4, n = 30) has been conducted. The expression of cytokine genes was analyzed by quantitative real-time PCR in the subjects' PBMCs, and the serum level of TGFß2 was measured by ELISA. Our findings showed that the expression level of the TGIF1 transcript was lower in cirrhotic and fibrotic patients compared to no fibrosis patients (p = 0.046 and 0.022, respectively). Also, there was an upregulation of the TGFß1 gene in cirrhotic patients relative to fibrotic patients (p = 0.015). Additionally, the cirrhotic patients had higher expression levels of the TGF-ß2 transcript and elevated levels of the TGF-ß2 protein than patients with no cirrhosis or fibrosis. According to the ROC analysis, TGFß1, TGIF1 transcripts, and TGFß2 protein have a good discriminatory performance in distinguishing between cirrhotic, fibrotic, and non-fibrotic patients. Our results suggested that the expression of TGIF1, TGF-ß1, and TGF-ß2 genes in PBMCs may provide a valuable tool for identifying patients with advanced cirrhosis and that TGF-ß and TGIF1 may be potential biomarkers for cirrhosis. These findings may have implications for the diagnosis and treatment of cirrhosis in HCV patients.

Abbreviated Urine Collection Compared With 24-Hour Urine Collection for Measuring Creatinine Clearance in Adult Critically Ill Patients: A Systematic Review.

OBJECTIVE: To evaluate the accuracy of abbreviated urine collection (≤12 hours) compared with 24-hour urine collection for measuring creatinine clearance (CrCl) in critically ill adult patients. DATA SOURCES: We searched PubMed, Embase, Web of Science, Google Scholar, and ProQuest Dissertations and Thesis Global; screened reference lists of included studies; and contacted the authors when needed. English studies only were considered with no restriction on dates. STUDY SELECTION AND DATA EXTRACTION: After duplicate removal, 2 reviewers screened titles/abstracts, reviewed full-text articles, and extracted data independently. Studies that compared abbreviated versus 24-hour urine collection for measuring CrCl were included. We assessed the risk of bias using the QUADAS-2 tool. We extracted correlation coefficients, mean prediction errors (ME)-as a measure of bias, and root mean squared prediction errors (RMSE)-as a measure of precision. DATA SYNTHESIS: Five studies were included, comprising 528 adult critically ill adults from surgical, medical, and trauma intensive care units (ICUs). Three studies had high risk of bias, and 2 had low risk. The studies evaluated different durations of urine collection, including 30-minute, 2-hour, 4-hour, 6-hour, and 12-hour. Mean 24-hour CrCl ranged from 57 mL/min/1.73 m2 to 103 mL/min. Abbreviated urine collection led to CrCl that correlated well with the 24-hour measured CrCl (correlation coefficient ranged from 0.8 to 0.95). Mean prediction error ranged from 5 mL/min/1.73 m2 to 16 mL/min (from 8% to 25% of the 24-hour CrCl). Root mean squared prediction error calculated from 1 study was 30.5 mL/min/1.73 m2. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Abbreviated urine collection is used to measure CrCl for renal drug dosing in critically ill patients, but its accuracy is not well-established. CONCLUSIONS: Abbreviated urine collection may overestimate CrCl compared with 24-hour urine collection. Larger, well-conducted studies are needed to evaluate the accuracy of CrCl measured using different durations of urine collection in critically ill patients.

A study of the association between single nucleotide polymorphisms of the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene and the risk of ankylosing spondylitis in Egyptians.

BACKGROUND: Ankylosing spondylitis (AS) is often regarded as the prototypical manifestation of spondylo-arthropathies that prevalently involves the axial skeleton with the potential attribution of ERAP2 polymorphisms to AS predisposition. The purpose of this study was to determine the genetic association between ERAP2 gene rs2910686, and rs2248374 single nucleotide polymorphisms (SNPs) and the risk of ankylosing spondylitis in the Egyptian population. METHODS AND RESULTS: A cross-sectional work involved 200 individuals: 100 AS individuals diagnosed based on modified New York criteria in 1984 with 100 healthy controls matched in age and gender. The study included a comprehensive evaluation of historical data, clinical examinations, and evaluation of the activity of the disease using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). A comprehensive laboratory and radiological evaluation were conducted, accompanied by an assessment and genotyping of the ERAP2 gene variants rs2248374 and rs2910686. This genotyping was performed utilizing a real-time allelic discrimination methodology.Highly statistically substantial variations existed among the AS patients and the healthy control group regarding rs2910686 and rs2248374 alleles. There was a statistically significant difference between rs2910686 and rs2248374 regarding BASDAI, BASFI, mSASSS, ASQoL, V.A.S, E.S.R, and BASMI in the active AS group. CONCLUSIONS: ERAP2 gene SNPs have been identified as valuable diagnostic biomarkers for AS patients in the Egyptian population being a sensitive and non-invasive approach for AS diagnosis especially rs2910686. Highly statistically significant variations existed among the AS patients and the healthy control group regarding rs2910686 alleles and genotypes.Further research is recommended to explore the potential therapeutic implications of these SNPs.

Side-specific factors for intraoperative hemodynamic instability in laparoscopic adrenalectomy for pheochromocytoma: a comparative study.

BACKGROUND: Adrenalectomy for pheochromocytoma (PHEO) is challenging because of the high risk of intraoperative hemodynamic instability (HDI). This study aimed to compare the incidence and risk factors of intraoperative HDI between laparoscopic left adrenalectomy (LLA) and laparoscopic right adrenalectomy (LRA). METHODS: We retrospectively analyzed two hundred and seventy-one patients aged > 18 years with unilateral benign PHEO of any size who underwent transperitoneal laparoscopic adrenalectomy at our hospitals between September 2016 and September 2023. Patients were divided into LRA (N = 122) and LLA (N = 149) groups. Univariate and multivariate logistic regression analyses were used to predict intraoperative HDI. In multivariate analysis for the prediction of HDI, right-sided PHEO, PHEO size, preoperative comorbidities, and preoperative systolic blood pressure were included. RESULTS: Intraoperative HDI was significantly higher in the LRA group than in the LLA (27% vs. 9.4%, p < 0.001). In the multivariate regression analysis, right-sided tumours showed a higher risk of intraoperative HDI (odds ratio [OR] 5.625, 95% confidence interval [CI], 1.147-27.577, p = 0.033). The tumor size (OR 11.019, 95% CI 3.996-30.38, p < 0.001), presence of preoperative comorbidities [diabetes mellitus, hypertension, and coronary heart disease] (OR 7.918, 95% CI 1.323-47.412, p = 0.023), and preoperative systolic blood pressure (OR 1.265, 95% CI 1.07-1.495, p = 0.006) were associated with a higher risk of HDI in both LRA and LLA, with no superiority of one side over the other. CONCLUSION: LRA was associated with a significantly higher intraoperative HDI than LLA. Right-sided PHEO was a risk factor for intraoperative HDI.

The Effect of Virtual Reality Application on Pain and Anxiety During Episiotomy Repair: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION AND HYPOTHESIS: There is a rising trend among women towards nonpharmacological approaches owing to their minimally invasive nature and limited adverse effects. Virtual reality (VR) has recently gained popularity as a new technology for reducing pain and anxiety in medical settings. Our research sought to investigate the impact of VR on pain and anxiety levels while undergoing episiotomy repair. METHODS: A comprehensive search was carried out across PubMed, Scopus, Cochrane Library, and ISI Web of Science to find relevant randomized clinical trials (RCTs) up to January 2024. These trials investigated the use of VR as a treatment during episiotomy repair compared with a control group that did not receive VR intervention. Meta-analysis was performed using Review Manager software to analyze the data collected. Our primary outcomes were pain scores reported during and after episiotomy repair measured by a visual analog scale. Secondary outcomes analyzed included anxiety scores during and after the procedure, as well as the duration of episiotomy repair. RESULTS: Seven RCTs, involving 578 patients, met the inclusion criteria. VR resulted in a significant reduction in pain scores both during and after episiotomy repair (p < 0.001). Additionally, anxiety levels during and after the procedure were significantly reduced in the VR group compared with the control group. Moreover, the duration of episiotomy repair was significantly shorter in the VR group. CONCLUSION: Using VR has proven to be an effective technique in reducing pain and anxiety during and after episiotomy repair, as well as potentially speeding up the procedure.

The effects of dexmedetomidine on intraoperative neurophysiologic monitoring modalities during corrective scoliosis surgery in pediatric patients: A systematic review.

BACKGROUND: During scoliosis surgery, motor evoked potentials (MEP), and somatosensory evoked potentials (SSEP) have been reported to be affected by the use of higher doses of anesthetic agents. Dexmedetomidine, a sympatholytic agent, an alpha-2 receptor agonist, has been used as an adjunctive agent to lower anesthetic dose. However, there is conflicting evidence regarding the effects of dexmedetomidine on the intraoperative neurophysiological monitoring of MEP and SSEP during surgery, particularly among pediatric patients. OBJECTIVES: This systematic review aimed to determine whether, during spinal fusion surgery in pediatric patients with scoliosis, dexmedetomidine alters MEP amplitude or SSEP latency and amplitude and, if so, whether different doses of dexmedetomidine display different effects (PROSPERO registration number CRD42022300562). METHODS: We searched PubMed, Scopus, and Cochrane Library on January 1, 2022 and included randomized controlled trials, observational cohort and case-control studies and case series investigating dexmedetomidine in the population of interest and comparing against a standardized anesthesia regimen without dexmedetomidine or comparing multiple doses of dexmedetomidine. Animal and in vitro studies and conference abstracts were excluded. RESULTS: We found substantial heterogeneity in the risk of bias (per Cochrane-preferred tools) of the included articles (n = 5); results are summarized without meta-analysis. Articles with the lowest risk of bias indicated that dexmedetomidine was associated with MEP loss and that higher doses of dexmedetomidine increased risk. In contrast, articles reporting no association between dexmedetomidine and MEP loss suffered from higher risk of bias, including suspected or confirmed problems with confounding, outcome measurement, participant selection, results reporting, and lack of statistical transparency and power. CONCLUSION: Given the limitations of the studies available in the literature, it would be advisable to conduct rigorous randomized controlled trials with larger sample sizes to assess the effects of dexmedetomidine use of in scoliosis surgery in pediatric patients.

Green and sensitive detection of olopatadine in aqueous humor using a signal-on fluorimetric approach: GREEnness assessment.

Olopatadine (OLP) is widely utilized as an effective antihistaminic drug for alleviating ocular itching associated with allergic conjunctivitis. With its frequent usage in pharmacies, there arises a pressing need for a cost-effective, easily implementable, environmentally sustainable detection method with high sensitivity. This study presents a novel signal-on fluorimetric method for detecting OLP in both its pure form and aqueous humor. The proposed approach depends on enhancing the weak intrinsic fluorescence emission of OLP, achieving a remarkable increase of up to 680% compared to its intrinsic fluorescence. This enhancement is achieved by forming micelles around protonated OLP using an acetate buffer (pH 3.6) and incorporating a solution of sodium dodecyl sulfate (SDS) surfactant. A strong correlation (R = 0.9996) is observed between the concentration of OLP and fluorescence intensities ranging from 1.0 to 100.0 ng mL-1 with a limit of detection of 0.22 ng mL-1. This described method is successfully employed for quantifying OLP in both its powder form and pharmaceutical eye drops. Furthermore, it demonstrates robust performance in determining OLP in artificial aqueous humor with a percentage recovery of 99.05 ± 1.51, with minimal interference from matrix interferents. Moreover, the greenness of the described method was evaluated.

Comparative study of laparoscopic ventral mesh rectopexy versus perineal stapler resection for external full-thickness rectal prolapse in elderly patients: enhanced outcomes and reduced recurrence rates-a retrospective cohort study.

BACKGROUND: In elderly patients with external full-thickness rectal prolapse (EFTRP), the exact differences in postoperative recurrence and functional outcomes between laparoscopic ventral mesh rectopexy (LVMR) and perineal stapler resection (PSR) have not yet been investigated. METHODS: We conducted a retrospective multicenter study on 330 elderly patients divided into LVMR group (n = 250) and PSR (n = 80) from April 2012 to April 2019. Patients were evaluated before and after surgery by Wexner incontinence scale, Altomare constipation scale, and patient satisfaction questionnaire. The primary outcomes were incidence and risk factors for EFTRP recurrence. Secondary outcomes were postoperative incontinence, constipation, and patient satisfaction. RESULTS: LVMR was associated with fewer postoperative complications (p < 0.001), lower prolapse recurrence (p < 0.001), lower Wexner incontinence score (p = 0.03), and lower Altomare's score (p = 0.047). Furthermore, LVMR demonstrated a significantly higher surgery-recurrence interval (p < 0.001), incontinence improvement (p = 0.019), and patient satisfaction (p < 0.001) than PSR. Three and 13 patients developed new symptoms in LVMR and PSR, respectively. The predictors for prolapse recurrence were LVMR (associated with 93% risk reduction of recurrence, OR 0.067, 95% CI 0.03-0.347, p = 0.001), symptom duration (prolonged duration was associated with an increased risk of recurrence, OR 1.131, 95% CI 1.036-1.236, p = 0.006), and length of prolapse (increased length was associated with a high recurrence risk (OR = 1.407, 95% CI = 1.197-1.655, p < 0.001). CONCLUSIONS: LVMR is safe for EFTRP treatment in elderly patients with low recurrence, and improved postoperative functional outcomes. TRIAL REGISTRATION: Clinical Trial.gov (NCT05915936), retrospectively registered on June 14, 2023.

Impact of a comprehensive rehabilitation palliative care program on the quality of life of patients with terminal cancer and their informal caregivers: a quasi-experimental study.

BACKGROUND: Palliative care schemes, which include pain management, symptom control, psychosocial support and rehabilitation, aim to boost patients' quality of life, ease the burden and anxiety of informal caregivers, and ultimately provide a comprehensive approach to enhance well-being during this challenging and sensitive period. This study aims to evaluate the impact of a comprehensive rehabilitation palliative care program on the quality of life of patients with terminal cancer and their informal caregivers. METHODS: This quasi-experimental study, conducted from August 2023 to January 2024 at outpatient clinics affiliated with the Oncology Center at Mansoura University, Egypt, focused on cancer patients and their caregivers in the palliative care department. Employing pre- and post-test phases, data were gathered using a questionnaire, EORTC QLQ C30, Hospital Anxiety and Depression Scale, Short Form Health Survey, Caregiver Burden Inventory, and Beck Anxiety Inventory. The investigation evaluated a 16-week rehabilitation program comprising exercise, psychoeducation, individual counselling, and spiritual support. Exercises, led by a physiotherapist, targeted fatigue and stress through tailored aerobic and resistance training. Psychoeducation sessions aimed to bolster coping abilities, covering fatigue management and nutrition. Trained counsellors addressed spiritual and existential concerns. Personal advisory sessions were available for individual support. Caregivers received education on rehabilitation and palliative care protocols, ensuring comprehensive patient care. RESULTS: The mean age for cancer patients was 65.79 ± 13.85. In contrast, the mean age for primary carers was 42.05 ± 11.15. The QOL for cancer patients during the pre-test phase was 77.8 ± 7.16 and rose to 87.34 ± 14.56 during the post-test phase. Additionally, the total anxiety level of patients before the rehabilitation palliative care program was conducted was 15.45 ± 3.05 compared to 6.12 ± 3.21 after the post test phase. Furthermore, the total depression levels of the patients during the pre-test phase were 20.89 ± 9.21. However, after implementing the rehabilitation palliative care program, it decreased to 15.5 ± 6.86. In regards to the total quality of life of informal caregivers, it was measured at 67.28 ± 32.09 before conducting the program. Nevertheless, it increased to 25.95 ± 40.29 after conducting it. Additionally, the total Caregiver Burden Inventory before implementing the program was 37.45 ± 25.7, and it decreased to 29.36 ± 16.4 after conducting it. Additionally, the total score on the Beck Anxiety Inventory decreased from 45.7 ± 4.3 during the initial testing phase to 17.35 ± 23.67. CONCLUSION: The program for rehabilitation palliative care successfully achieved its goals by enhancing the overall quality of life for cancer patients and their caregivers. Additionally, it reduced the anxiety and depression levels among the patients, as well as the anxiety and caregiver burden among the caregivers. Continue research into the effectiveness of rehabilitation palliative care programs to identify best practices, improve existing programs, and expand access to these services.

Balancing confidentiality and care coordination: challenges in patient privacy.

BACKGROUND: In the digital age, maintaining patient confidentiality while ensuring effective care coordination poses significant challenges for healthcare providers, particularly nurses. AIM: To investigate the challenges and strategies associated with balancing patient confidentiality and effective care coordination in the digital age. METHODS: A cross-sectional study was conducted in a general hospital in Egypt to collect data from 150 nurses across various departments with at least six months of experience in patient care. Data were collected using six tools: Demographic Form, HIPAA Compliance Checklist, Privacy Impact Assessment (PIA) Tool, Data Sharing Agreement (DSA) Framework, EHR Privacy and Security Assessment Tool, and NIST Cybersecurity Framework. Validity and Reliability were ensured through pilot testing and factor analysis. RESULTS: Participants were primarily aged 31-40 years (45%), with 75% female and 60% staff nurses. High compliance was observed in the HIPAA Compliance Checklist, especially in Administrative Safeguards (3.8 ± 0.5), indicating strong management and training processes, with an overall score of 85 ± 10. The PIA Tool showed robust privacy management, with Project Descriptions scoring 4.5 ± 0.3 and a total score of 30 ± 3. The DSA Framework had a mean total score of 20 ± 2, with Data Protection Measures scoring highest at 4.0 ± 0.4. The EHR assessments revealed high scores in Access Controls (4.4 ± 0.3) and Data Integrity Measures (4.3 ± 0.3), with an overall score of 22 ± 1.5. The NIST Cybersecurity Framework had a total score of 18 ± 2, with the highest scores in Protect (3.8) and lower in Detect (3.6). Strong positive correlations were found between HIPAA Compliance and EHR Privacy (r = 0.70, p < 0.05) and NIST Cybersecurity (r = 0.55, p < 0.05), reflecting effective data protection practices. CONCLUSION: The study suggests that continuous improvement in privacy practices among healthcare providers, through ongoing training and comprehensive privacy frameworks, is vital for enhancing patient confidentiality and supporting effective care coordination.

Diagnostic validity and reliability of BT-RADS in the management of recurrent high-grade glioma.

BACKGROUND AND PURPOSE: BT-RADS is a new framework system for reporting the treatment response of brain tumors. The aim of the study was to assess the diagnostic performance and reliability of the BT-RADS in predicting the recurrence of high-grade glioma (HGG). MATERIALS AND METHODS: This prospective single-center study recruited 81 cases with previously operated and pathologically proven HGG. The patients underwent baseline and follow-up contrast-enhanced MRI (CE-MRI). Two neuro-radiologists with ten years-experience in neuroimaging independently analyzed and interpreted the MRI images and assigned a BT-RADS category for each case. To assess the diagnostic accuracy of the BT-RADS for detecting recurrent HGG, the reference standard was the histopathology for BT-RADS categories 3 and 4, while neurological clinical examination and clinical follow up were used as a reference for BT-RADS categories 1 and 2. The inter-reader agreement was assessed using the Cohen's Kappa test. RESULTS: The study included 81 cases of HGG, of which 42 were recurrent and 39 were non-recurrent HGG cases based on the reference test. BT-RADS 3B was the best cutoff for predicting recurrent HGG with a sensitivity of 90.5 % to 92.9 %, specificity of 76.9 % to 84.6 %, and accuracy of 83.9 % to 88.9 %, based on both readers. The BT-RADS showed a substantial inter-reader agreement with a K of 0.710 (P = 0.001). CONCLUSIONS: The BT-RADS is a valid and reliable framework for predicting recurrent HGG. Moreover, BT-RADS can help neuro-oncologists make clinical decisions that can potentially improve the patient's outcome.

Zirconium-Directed Supramolecular Self-Assembly of Coenzyme A@GNCs with Enhanced Phosphorescence for Developing Ultrasensitive Tracer Probe of Dipicolinic Acid, a Biomarker of Bacterial Spores.

Luminescent gold nanoclusters (GNCs) are a class of attractive quantum-sized nanomaterials bridging the gap between organogold complexes and gold nanocrystals. They typically have a core-shell structure consisting of a Au(I)-organoligand shell-encapsulated few-atom Au(0) core. Their luminescent properties are greatly affected by their Au(I)-organoligand shell, which also supports the aggregation-induced emission (AIE) effect. However, so far, the luminescent Au nanoclusters encapsulated with the organoligands containing phosphoryl moiety have rarely been reported, not to mention their AIE. In this study, coenzyme A (CoA), an adenosine diphosphate (ADP) analogue that is composed of a bulky 5-phosphoribonucleotide adenosine moiety connected to a long branch of vitamin B5 (pantetheine) via a diphosphate ester linkage and ubiquitous in all living organisms, has been used to synthesize phosphorescent GNCs for the first time. Interestingly, the synthesized phosphorescent CoA@GNCs could be further induced to generate AIE via the PO32- and Zr4+ interactions, and the observed AIE was found to be highly specific to Zr4+ ions. In addition, the enhanced phosphorescent emission could be quickly turned down by dipicolinic acid (DPA), a universal and specific component and also a biomarker of bacterial spores. Therefore, a Zr4+-CoA@GNCs-based DPA biosensor for quick, facile, and highly sensitive detection of possible spore contamination has been developed, showing a linear concentration range from 0.5 to 20 µM with a limit of detection of 10 nM. This study has demonstrated a promising future for various organic molecules containing phosphoryl moiety for the preparation of AIE-active metal nanoclusters.

Different additives of gold nanoparticles and lithium oxide loaded chitosan based films; controlling optical and structural properties, evaluating cell viability.

Natural chitosan-based films (CS) were fabricated by changing ingredient corporations between gold nanoparticles (AuNPs), lithium oxide (Li2O), and graphene oxide (GO). A Series of films with different components were obtained. The structural examination is executed by XRD, FTIR, and EDX to analyze crystal structure, chemical bonding, and chemical contents, respectively. The findings illustrated that, the Li2O@CS exhibited the lowest contact angle with 70 ± 4.6°. Scanning Electron Microscopy (SEM) displayd rod-shaped AuNPs with an average length of 0.3 µm and an average width of 90 nm. The refractive index of CS recorded 2.142, while AuNPs/Li2O/GO@CS slightly declined to 2.085. Concerning AuNPs/Li2O/GO@CS, the detected cell viability percentage of normal lung cells among the usage of 156.25 µg/mL is 98.91%, while 9.77 µg/mL achieved 125.78%. Therefore, combining AuNPs, GO and Li2O within the CS matrix results in films of boosted biocompatibility and can be suggested for medical applications.

Does Growth Velocity Affect Associations between Birth Weight and Neurodevelopment for Infants Born Very Preterm?

OBJECTIVE: To determine how neonatal growth velocity affects the association between birth weight and neurodevelopmental outcomes in infants born preterm. STUDY DESIGN: This study is a secondary analysis of the Maternal Omega-3 Supplementation to Reduce Bronchopulmonary Dysplasia in Very Preterm Infants (MOBYDIck) randomized multicenter trial conducted in breastfed infants born at <29 weeks of gestation, whose mothers were supplemented with docosahexaenoic acid or placebo during the neonatal period. Neurodevelopmental outcomes were assessed at 18-22 months of corrected age using the Bayley-III cognitive and language composite scores. The role of neonatal growth velocity was assessed with causal mediation and linear regression models. Subgroup analyses were stratified by birth weight z-score categories (<25th, ≥25th-≤75th, and >75th percentiles). RESULTS: Neurodevelopmental outcomes were available for 379 children (mean gestational age, 26.7 ± 1.5 weeks). Growth velocity partially mediated the relationships between birth weight and cognitive (ß = -1.1; 95% CI, -2.2 to -0.02; P = .05) and language scores (ß = -2.1; 95% CI, -3.3 to -0.8; P = .002). An increase by 1 g/kg/day in growth velocity was associated with an increase by 1.1 point in the cognitive score (95% CI, -0.03 to 2.1; P = .06) and 1.9 point in the language score (95% CI, 0.7 to 3.1; P = .001), after adjustment for birth weight z-score. For children with birth weight <25th percentile, a 1 g/kg/day increase in growth velocity was associated with an increase by 3.3 points in the cognitive score (95% CI, 0.5 to 6.0; P = .02) and 4.1 points in the language score (95% CI, 1.3 to 7.0; P = .004). CONCLUSIONS: Postnatal growth velocity mediated the relationship between birth weight and neurodevelopmental performance, with larger effects for children with lower birth weight. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02371460.

SARS-CoV-2 virus associated angiotensin converting enzyme 2 expression modulation in colorectal cancer: Insights from mRNA and protein analysis COVID-19 associated (ACE2) expression in colorectal cancer.

The SARS-CoV-2 virus gains entry into human cells by exploiting the angiotensin-converting enzyme 2 (ACE2), a key component known as the spike protein (S), as a point of entry. Initially, SARS-CoV-2 suppresses the natural function of ACE2, leading to a gradual decline in cell health. Additionally, individuals with cancer are considered more susceptible to COVID-19. This study investigates the expression patterns of ACE2 in colorectal cancer (CRC) patients with and without a history of COVID-19 infection. RT-PCR was used to analyze samples from both cancerous and adjacent non-affected colorectal tissues of 47 CRC patients, comprising two groups: 24 CRC patients with no history of COVID-19 and 23 CRC patients with a recent history of COVID-19 infection. Epithelial CR cells were isolated from both types of tissues and cultured to evaluate cell adhesion. Immunohistochemistry analyses were conducted to examine ACE2 protein expression using various ACE2 antibodies for both cell types. The study revealed ACE2 mRNA expression in all CRC tissues of patients with and without a history of COVID-19. ACE2 expression was significantly higher in CRC patients without a history of COVID-19. Notably, the non-affected colorectal cancer (NACRC) tissues of patients without a history of COVID-19 also showed ACE2 expression, whereas no ACE2 expression was detected in the biopsies of CRC patients with a positive COVID-19 history. ACE2 antibodies were employed to validate ACE2 protein expression at the mRNA level. COVID-19 appears to downregulate ACE2 expression in both CRC and NACRC tissues of CRC patients with a positive history of COVID-19 infection.

Patterns of mutations in nine cancer-related genes and PAF development among smoking male patients diagnosed with bladder cancer.

BACKGROUND: Smoking is one of the most popular risk factors provoking bladder cancer (BC). This research intended to estimate cigarette smoking effect involving PAF signs between smoking patients with BC and non-smoking patients with same diagnosis to define relations with pathological characteristics and their prognosis on zero-relapse and disease-associated recovery. METHODS: Two groups of smokers (n = 54) and non-smokers (n = 62) were selected. Both cohorts of patients had BC. They were evaluated utilizing NGS on 9 cancer-related genes and confirmed through the Sanger DNA sequencing and histopathological tests based on H&E staining. The factor of smoking and impact of PAF development by ELISA assay and PAF-R manifestation in terms of immunochemical evaluation on BC areas comparing to a control group (n = 30) was examined involving healthy contributors, including the use of well-designed statistical trials. RESULTS: The multivariate evaluation showed considerable rise in mutation patterns related to smoking among BC patients (group 3), increase in PAF development (***P<0.001) and vivid signs of PAF-R contrasted to non-smokers with BC (group 2) and control group (group 1). All the identified biological changes (gains/losses) were recorded at the same locations in both groups. Patients from group 3 held 3-4 various mutations, while patients from group 2 held 1-3 various mutations. Mutations were not identified in 30 respondents from control group. The most repeated mutations were identified in 3 of 9 examined genes, namely TP53, PIK3CA and PTEN, with highest rates of increase in Group 3. Moreover, histopathological tests revealed barely identifiable and abnormal traits in BC tissues, i.e. were without essential histopathological changes between groups 2 and 3. CONCLUSION: Smoking of cigarettes provokes PAF development due to urothelial inflammation and rise of mutations in 9 cancer-related genes. These are indicative factors of inducing BC.

Quantitative Gait and Balance Outcomes for Ataxia Trials: Consensus Recommendations by the Ataxia Global Initiative Working Group on Digital-Motor Biomarkers.

With disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid, finely granulated, digital health measures are highly warranted to augment clinical and patient-reported outcome measures. Gait and balance disturbances most often present as the first signs of degenerative cerebellar ataxia and are the most reported disabling features in disease progression. Thus, digital gait and balance measures constitute promising and relevant performance outcomes for clinical trials.This narrative review with embedded consensus will describe evidence for the sensitivity of digital gait and balance measures for evaluating ataxia severity and progression, propose a consensus protocol for establishing gait and balance metrics in natural history studies and clinical trials, and discuss relevant issues for their use as performance outcomes.

Three cases of colon cancer in four generations of the Saudi family, caused by endogamous germline mutations.

Various research pieces of evidence have been published in recent years, establishing the increasing prevalence of early colon cancer among young people. In this background, the current study aimed to analyze the reasons behind colon cancer recurrence among endogamous consanguineous cases in four generations of a single Saud family. For this study, the authors conducted the whole-exome sequencing analysis to screen for germline mutations in DNA samples from consanguineous cases within the family. After collecting the colon samples, it was analyzed histologically and immunohistochemically with the help of Breast Cancer antibodies (BRCA2 and 1 correspondingly) and H&M staining (hematoxylin and eosin). For this study, 26 at-risk consanguineous cases were considered. Three cases were diagnosed with malignant colon cancer, two with breast cancer, and 17 with germline mutations, yet remain unaffected by cancerous tumors. The rest, four consanguineous cases, are healthy and non-carriers of the mutations. However, as per the exome analysis outcomes, 15 cases inherited germline mutations in nine genes. Nine substitution mutations were present in six of the nine inherited genes in these inherited germline mutations. Furthermore, it also presented six insertion and deletion frameshift mutations in five of nine inherited genes. The immunohistochemical staining process achieved positive staining outcomes for BRCA1 and 2. Therefore, germline mutations inherited from the nine genes of endogamous consanguineous cases of mutation carriers remain the primary reason behind colon cancer recurrence in the same family.

Synthesis and characterization of Hypsizygus ulmarius extract mediated silver nanoparticles (AgNPs) and test their potentiality on antimicrobial and anticancer effects.

The prime aim of this research is to discover new, eco-friendly approaches to reducing agents for manufacturing silver nanoparticles (AgNPs) from fresh fruiting bodies of the edible mushroom Hypsizygus ulmarius (Hu). The confirmation of Hu-mediated AgNPs has been characterized by UV visible spectroscopy, XRD, FTIR, SEM with EDX, HRTEM, AFM, PSA, Zeta poetical and GCMS analysis. The absorption peak of Hu-AgNPs at 430 nm has been confirmed by UV-visible spectroscopy analysis. The findings of the particle size study show that AgNPs have a size distribution with an average of 20 nm. The Zeta potential of NPs reveals a significant build-up of negative charges on their surface. The additional hydrate layers that occurred at the surface of AgNPs are shown in the HR-TEM morphology images. The antibacterial activity results showed that Hu-AgNPs were highly effective against both bacterial pathogens, with gram-positive (+) and gram-negative (-) pathogens having a moderate inhibition effect on K. pneumoniae (5.3 ± 0.3 mm), E. coli (5.3 ± 0.1), and S. aureus (5.2 ± 0.3 mm). Hu-AgNPs (IC50 of 50.78 µg/mL) were found to have dose-dependent cytotoxic action against human lung cancer cell lines (A549). Inhibited cell viability by up to 64.31% after 24 h of treatment. To the best of our knowledge, this is the hand information on the myco-synthesis of AgNPs from the H. ulmarius mushroom extract and the results suggest that it can an excellent source for developing a multipurpose and eco-friendly nano product in future.

Protocatechuic acid ameliorates lipopolysaccharide-induced kidney damage in mice via downregulation of TLR-4-mediated IKBKB/NF-κB and MAPK/Erk signaling pathways.

Acute kidney injury (AKI) is a very critical cause of death in the whole world. Lipopolysaccharide (LPS) induces kidney damage by activating various deleterious inflammatory and oxidative pathways. Protocatechuic acid, a natural phenolic compound, has shown to exert beneficial effects against oxidative and inflammatory responses. The study aimed to clarify the nephroprotective activity of protocatechuic acid in LPS-induced acute kidney damage in mice. Forty male Swiss mice were allocated in four groups as follows: normal control group; LPS (250 µg/kg, ip)-induced kidney injury group; LPS-injected mice treated with protocatechuic acid (15 mg/kg, po), and LPS-injected mice treated with protocatechuic acid (30 mg/kg, po). Significant toll-like receptor 4 (TLR-4)-mediated activation of IKBKB/NF-κB and MAPK/Erk/COX-2 inflammatory pathways has been observed in kidneys of mice treated with LPS. Oxidative stress was revealed by inhibition of total antioxidant capacity, catalase, nuclear factor erythroid 2-related factor 2 (Nrf2), and NAD(P)H quinone oxidoreductase (NQO1) enzyme along with increased nitric oxide level. In parallel, focal inflammatory effects were shown in between the tubules and glomeruli as well as in the perivascular dilated blood vessels at the cortex affecting the normal morphology of the kidney tissues of LPS-treated mice. However, treatment with protocatechuic acid reduced LPS-induced changes in the aforementioned parameters and restored normal histological features of the affected tissues. In conclusion, our study uncovered that protocatechuic acid has nephroprotective effects in mice with AKI through opposing different inflammatory and oxidative cascades.