Circulating-tumour DNA methylation of HAND1 gene: a promising biomarker in early detection of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the significant global health concerns with an increase in cases. Regular screening tests are crucial for early detection as it is often asymptomatic in the initial stages. Liquid biopsies, a non-invasive approach that examines biomarkers in biofluids, offer a promising future in diagnosing and screening cancer. Circulating-tumour DNA (ctDNA) is the genetic material in biofluids released into the circulatory system by cells. ctDNA is a promising marker for monitoring patients since cancer cells display distinct DNA methylation patterns compared to normal cells. The potential of our research to contribute to early detection and improved patient outcomes is significant. AIMS: The primary objective of this research project was to explore the HAND1 methylation levels in plasma ctDNA as a potential biomarker for diagnosing CRC and evaluate the methylation level of the well-established gene SPET9 to compare it with the methylation level of HAND1. MATERIALS AND METHODS: Plasma samples were collected from 30 CRC patients and 15 healthy individuals, with CRC samples obtained pre-treatment. ctDNA was extracted and treated with bisulfite for methylation status assessment. Quantitative methylation-specific PCR (qMS-PCR) was performed for HAND1 and SEPT9, using ß-actin (ACTB gene) as a reference. The study aims to evaluate the potential of these genes as diagnostic biomarkers for CRC, contributing to early detection and improved patient outcomes. RESULTS: Our study yielded significant results: 90% of CRC patients (27 out of 30) had hypermethylation in the SEPT9 gene, and 83% (25 out of 30) exhibited hypermethylation in the HAND1 gene. The methylation levels of both genes were significantly higher in CRC patients than in healthy donors. These findings underscore the potential of SEPT9 and HAND1 methylation as promising biomarkers for diagnosing CRC, potentially leading to early detection and improved patient outcomes. CONCLUSION: These findings highlight the potential of SEPT9 and HAND1 methylation as promising biomarkers for diagnosing CRC. However, further research and validation studies are needed to confirm these findings and to explore their clinical utility in CRC diagnosis and management.

Investigating FGFR2 gene as a blood-based epigenetic biomarker in gastric cancer.

BACKGROUND: Gastric adenocarcinoma is a prevalent form of cancer that often remains undetected in its early stages due to the lack of specific symptoms. This delayed diagnosis leads to poor clinical outcomes, underscoring the need for an effective and non-invasive method for early detection. Recent advances in cancer epigenetics have led to the identification of biomarkers that have the potential to revolutionize the early detection and monitoring of this disease. One such promising biomarker is the methylation of the FGFR2 promoter. This study aims to measure the methylation levels of a specific CpG site in the FGFR2 promoter gene in DNA extracted from blood leukocytes from patients with intestinal metaplasia, gastric cancer, and healthy control. MATERIAL AND METHODS: The CpG site of the FGFR2 gene promoter was identified in its control region. Methylation alteration of the selected FGFR2 CpG site was determined through the (methylation-sensitive restriction enzyme) MSRE-qPCR. Genomic DNA was extracted from one hundred twenty-five participants. RESULTS: The normal group had mean methylation levels of 93.23 ± 4.929%, while the IM group had a level of 69.85 ± 27.15%. In GC patients, the levels varied, with 25.96 ± 18.98% in the intestinal type and 28.30 ± 16.07% in the diffuse type. The methylation levels in the IM and GC patients were significantly lower than those in the normal control group. However, no significant difference was observed between the methylation status of the intestinal type of GC and the diffuse type. The Receiver operating characteristic (ROC) curve analysis showed that FGFR2 CpG methylation levels in GC patients compared to normal controls had a high sensitivity of 100% and specificity of 100%, with a cut-off of < 74.25%; when GC patients were compared to IM patients, the sensitivity was 85%, and the specificity was 80%, with a cut-off < 44.45%. CONCLUSIONS: The potential of the FGFR2 methylation status as a non-invasive biomarker lies in its ability to be detected in blood leukocytes, which makes it a promising tool for the early detection of intestinal metaplasia and gastric cancer. This could significantly improve the detection and management of these gastric conditions.

Effect of Bacterial Phytase on Growth Performance, Nutrient Utilization, and Bone Mineralization in Broilers Fed Pelleted Diets.

The influence of a bacterial 6-phytase on growth performance, coefficient of apparent ileal digestibility (CAID) of nutrients, blood parameters, and bone mineralization in broilers was evaluated. A total of 630 one-day-old male broilers were allocated to 7 dietary treatments, including positive control (PC) diet containing dicalcium phosphate, the PC marginally reduced in available P (avP) by 0.1% and calcium (Ca) by 0.2% vs. PC (NC1) or moderately reduced by 0.15 and 0.3% vs. PC (NC2), respectively, and four further diets comprising the NC1 and NC2 supplemented with 500 or 1000 FTU/kg of phytase in starter and finisher phases. A constant Ca to avP ratio was maintained across all diets. The body weight gain (BWG) and feed per unit gain (FCR) of birds fed NC1 and NC2 diets supplemented with phytase (500 and 1000 U/kg) was equivalent to that of birds fed the PC diet at 35 days. Phytase supplementation in the NC1 diet linearly increased the CAID of nitrogen (N) (p < 0.01), phosphorus (P) (p < 0.01), and Ca (p < 0.05). Additionally, phytase reduced (p < 0.01) excreta P concentration by approximately 27%, improved (p < 0.001) toe ash, and tended to increase tibia ash (p = 0.08), comparable with the PC. In conclusion, the addition of bacterial 6-phytase dosed in the range of 500-1000 FTU/kg was effective in replacing 1.5 g/kg avP and 3 g/kg Ca in broilers fed pelleted diets, using bone quality, BWG, and FCR as outcome measures.

Preoperative Neutrophil: Lymphocyte Ratio, Platelet: Lymphocyte Ratio, and C-Reactive Protein Levels Predictive Value in Determining the Severity of Breast Mass.

Background & Objective: Female breast cancer is one of the most prevalent malignancies among women. The critical step in management of breast cancer is an accurate diagnosis. Hence, peripheral blood-based tests would be one of the most favorable and less invasive methods to study. Recent studies have investigated the inflammatory parameters such as neutrophil: lymphocyte ratio (NLR), the platelet: lymphocyte ratio (PLR), and the C-reactive protein (CRP) levels. The elevation in mentioned parameters was proposed as a key factor in cancer progression. The main goal of this study was to investigate the association of NLR, PLR, and CRP levels in patients with breast lesions. Methods: The NLR, PLR, and CRP levels were calculated from 200 female patients presenting with either benign or malignant lesions. Results: The cut-off values of NLR, PLR, and CRP were 1.24, 96, and 10.36 mg/L, respectively. A significant difference in NLR (P<0.001), PLR (P<0.001), and CRP levels (P<0.001) were observed between the two major studied cohorts. Conclusion: Elevated NLR, PLR, and CRP levels could predict the presence of malignancy. In addition to the low cost and properties of the mentioned methods, utilization of this data could facilitate and improve clinical decision-making for treatment.

Epigenteic Alteration of DOK7 Gene CpG Island in Blood Leukocyte of Patients with Gastric Cancer and Intestinal Methaplasia.

Background: Intestinal metaplasia (IM) is a benign lesion with no serious concern for patients' health. On the other hand, gastric cancer (GC) is a malignant lesion that has to be differentially diagnosed from benign intestinal metaplasia. Epigenetic modifications have been suggested to play an important role in cancer initiation and development, and they have been investigated as a reliable biomarker tool even for early cancer diagnosis. Whole blood leucocytes (WBC) are potentially the most accessible tissue for cancer early diagnosis, especially for GC, which is hard to diagnose in the early stage. Objective: This study aims to investigate the methylation status of DOK7 gene CpG island in blood leukocytes of patients with IM and GC compared to normal control groups. Material and Method: DNA was extracted from the whole blood of 30 IM patients, 30 GC patients, and 34 normal controls samples, and MSRE-PCR was utilized to evaluate the loci methylation status. Results: Significant hypermethylation of DOK7 gene CpG has been observed in GC 88.1 % (p < 0.001) and IM 66.0 % (p = 0.03) in comparison to the normal control group 56.8%. A cutoff upper than 84.5 % of hypermethylation is considered as a presence of gastric cancer malignant lesions. Conclusions: This is the first reported on hypermethylation in DOK7 CPG in blood leukocytes of patients with GC and IM and establishing a laboratory blood based test that may be useful as a novel biomarker test in the early diagnosis and screaning of GC and IM.

Consequences of aberrated DNA methylation in Colon Adenocarcinoma: a bioinformatic-based multi-approach.

INTRODUCTION: The biology of colorectal cancer (CRC) is remained to be elucidated. Numerous genetic and epigenetic modifications are in concert to create and progress CRC. DNA methylation as a principal epigenetic factor has gained increased attention and could be utilized for biological studies. This study aims to find novel methylated and downregulated genes with a focus on HAND2 in CRC and decipher the biological consequences. MATERIAL AND METHOD: Data on DNA methylation from GEO and SMART databases and the expression GEPIA2 database were downloaded. Afterward, a set of hypermethylated and downregulated genes in CRC was chosen by overlapping genes. Consequently, HAND2 was selected as a key gene for further investigation and confirmed with cell lines methylation and expression data. The functions of HAND2 were further analyzed using gene ontology analyses and the protein-protein interaction network. RESULTS: The methylation (p < 0.01) and expression (p < 0.01) of HAND2 are significantly varied in CRC compared to normal control. The correlation analysis (Pearson's correlation coefficient = -0.44, p = 6.6e-14) conveys that HAND2 significantly downregulated and has a reverse correlation with the methylation status of CpG islands. The biological process analysis of HAND2 target genes conveyed that disruption in HAND2 expression could dysregulate ERK1 and ERK2 signaling pathways. CONCLUSION: Together, the findings showed that DNA hypermethylation of HAND2 was critical evidence in CRC. Further validation and prospective studies are needed to utilize HAND2 methylation as a promising biomarker.

Folic Acid-Adorned Curcumin-Loaded Iron Oxide Nanoparticles for Cervical Cancer.

Cancer is a deadly disease that has long plagued humans and has become more prevalent in recent years. The common treatment modalities for this disease have always faced many problems and complications, and this has led to the discovery of strategies for cancer diagnosis and treatment. The use of magnetic nanoparticles in the past two decades has had a significant impact on this. One of the objectives of the present study is to introduce the special properties of these nanoparticles and how they are structured to load and transport drugs to tumors. In this study, iron oxide (Fe3O4) nanoparticles with 6 nm sizes were coated with hyperbranched polyglycerol (HPG) and folic acid (FA). The functionalized nanoparticles (10-20 nm) were less likely to aggregate compared to non-functionalized nanoparticles. HPG@Fe3O4 and FA@HPG@Fe3O4 nanoparticles were compared in drug loading procedures with curcumin. HPG@Fe3O4 and FA@HPG@Fe3O4 nanoparticles' maximal drug-loading capacities were determined to be 82 and 88%, respectively. HeLa cells and mouse L929 fibroblasts treated with nanoparticles took up more FA@HPG@Fe3O4 nanoparticles than HPG@Fe3O4 nanoparticles. The FA@HPG@Fe3O4 nanoparticles produced in the current investigation have potential as anticancer drug delivery systems. For the purpose of diagnosis, incubation of HeLa cells with nanoparticles decreased MRI signal enhancement's percentage and the largest alteration was observed after incubation with FA@HPG@Fe3O4 nanoparticles.

Presentation of the hypothenar hammer syndrome as a low incidence aneurysmal disorder of the ulnar artery.

INTRODUCTION AND IMPORTANCE: The hypothenar hammer syndrome (HHS) is either rare or underdiagnosed condition that arises from vascular insufficiency of the ulnar artery in the hand. The most common accused mechanism is repetitive blunt trauma to hypothenar region while activating the latter as a hammer to do the job. CASE PRESENTATION: A 48 year old woman worked as a master of university claimed from pain and numbness in her left hand concurrent with a pulsatile mass. The second case was a 48 year old man who was a mechanic engineer in automotive industry that claimed of a pain and pulsatile mass in his non-dominant left hand. CLINICAL DISCUSSION: Ulnar artery enters the hand from Guyon's canal where fixes to adjacent structure and is susceptible for injury. Aneurysmal formation is an outcome of arterial trauma which could result in distal necrosis if remains untreated. CONCLUSION: This study has revealed that even whether a single blunt trauma or writing with pen could lead to aneurysmal formation. It has also showed primary aneurysmal resection with no further surgical procedure is both safe and reliable if digital ischemia is not concurrently present.

Interactive effect of corn particle size and insoluble fiber source on performance, nutrient utilization and intestine morphology in broilers fed pelleted diets.

The effects of corn particle size and dietary fibre on the performance, coefficient of apparent ileal digestibility (CAID) and intestinal characteristics in broiler starters fed pelleted diets were studied. The experiment included 10 treatments arranged as a 2 × 5 factorial with two corn particle sizes (GMD of 1071 [CGC] vs. 534 [FGC]) and five diets that consisted in a low-fibre diet and four extra diets resulting from the inclusion of insoluble fibre sources (10 g/kg of lignocellulose (LC), and 30 g/kg of oat hulls; OH, rice hulls; RH, and sunflower hulls; SFH). In coarse grinding, all-fibre sources improved body weight gain and feed intake compared to the control diet (p < 0.01). Feed conversion ratio (FCR) improved with fibre supplementation (p < 0.01) and fine grinding of corn (FGC) (p < 0.01). Coarse grinding of corn (CGC) and inclusion of RH, SFH and OH reduced gizzard pH (p < 0.01). Fibre inclusion increased ileal fat and Ca digestibility (p < 0.01), gizzard weight (p < 0.01), digesta transit time (p < 0.01) and length of duodenum and small intestine (p < 0.01). The CAID of phosphorus increased in CGC fed birds and inclusion of RH, SFH and OH (p < 0.05). The weight of gizzard, proventriculus and pancreas (p < 0.01) was greater in CGC fed birds. Feeding SFH, RH and OH (p < 0.01), and CGC (p < 0.01) increased the villus height (VH) of the duodenum. The OH, RH and SFH supplementation increased the caecal population of Lactobacillus spp. and total anaerobic bacteria (p < 0.01) only in FGC fed birds. Overall, birds fed pelleted diets containing RH, OH and SFH (3%) exhibited improved performance, and increased nutrient digestibility, which may be caused by developed gizzards and intestine. Furthermore, coarse grinding of corn is beneficial to gizzard development.

The intracranial branch; A rare anatomical variation of the recurrent laryngeal nerve; Case report.

INTRODUCTION: The recurrent laryngeal nerve (RLN) originates from the Vagus nerve intrathoracically. It passes through the tracheoesophageal groove (TEG) in the neck and different variations in this section were observed. The RLN is at highest risk for injury during the thyroid surgery. Therefore, it is important to know variations to decrease the injury effectively. PRESENTATION OF CASE: A 50 years-old woman with no thyroid related complaints except for enlargement of the thyroid gland in recent 12-months that annoyed her during neck movement and for aesthetic features. Medical, surgical, drugs, irradiation history, laboratory data, and physical examination was unremarkable except for multi-lobulated enlarged thyroid gland. The CT scanning study revealed intrathoracic extension of the gland. Patient underwent total thyroidectomy with suspicious diagnosis of multinodular goiter which was confirmed later by pathologic study. Intraoperative exploration of the right RLN discovered an intracranial branch originating from the recurrent laryngeal trunk just beneath the inferior thyroid artery (ITA) at the level of the nerve intersection. The branch then passed laterally about 1 cm and penetrated in ipsilateral carotid sheath. DISCUSSION: The RLN has different anatomical variations in either the right or the left side of the neck. However extra-laryngeal nerve branching is the most common variation but other seldom variations including the non-RLN, and intracranial branch should be mentioned by surgeon intraoperatively. CONCLUSION: To decrease iatrogenic injuries to RLN and its associated nerve branches knowledge of the nerve anatomy is mandatory for surgeon to prevent morbid side effects.

Fracture resistance of pulpotomized and composite-restored primary molars: Incremental versus bulk-fill techniques.

BACKGROUND: The aim of this study was to assess the fracture resistance of pulpotomized primary molars restored with incremental and bulk-fill composite application techniques. MATERIALS AND METHODS: In this in-vitro experimental study, 36 extracted primary molars were nonrandomly (selectively) divided into three groups of 12 each. All teeth underwent conventional pulpotomy treatment, and mesio-occluso-distal cavities were prepared in such a way that the buccolingual width of the preparation was two-thirds of the intercuspal distance, and the depth of the buccal and lingual walls was 4 mm. The teeth were then restored as follows: Group 1 (control) was restored with amalgam, Group 2 was restored with Tetric N-Ceram composite using the incremental technique, and Group 3 was restored with Tetric N-Ceram composite using the bulk-fill technique. The restored teeth were subjected to thermocycling and then underwent fracture resistance testing in a universal testing machine at a crosshead speed of 1 mm/min. Fracture resistance of groups was compared using the one-way ANOVA and Tukey's honestly significant difference test. RESULTS: The mean fracture resistance was 1291.47 ± 603.88 N in the amalgam, 1283.08 ± 594.57 N in the Tetric N-Ceram incremental, and 1939.06 ± 134.47 N in the Tetric N-Ceram bulk-fill group. The difference in this regard between Group 3 and Groups 1 and 2 was statistically significant (P = 0.019 and P= 0.035, respectively). CONCLUSION: Bulk-fill composite is recommended for reinforcing the remaining tooth structure after the primary molar pulpotomy procedure. Time-saving characteristics of this material are clinically important for reducing appointment time for children.

Effects of vitamin A and vitamin E on attenuation of titanium dioxide nanoparticles-induced toxicity in the liver of male Wistar rats.

The increasing application of titanium dioxide nanoparticles (NTiO2) in life and the toxicity potential of these nanoparticles have raised concerns about their detrimental effects on human health. This study was conducted to investigate the hepatoprotective effects of vitamin E and vitamin A against hepatotoxicity induced by NTiO2 in rats. Thirty-six male Wistar rats were randomly divided into six groups of six rats each. Intoxicated group received 300 mg/kg NTiO2 for two weeks by gavage. Groups treated with vitamin E (100 IU/kg), vitamin A (100 IU/kg) and mixture of these vitamins were orally administered for 3 weeks (started 7 days before NTiO2 administration). In order to investigate the redox changes, total antioxidant capacity, total oxidant status, and lipid peroxidation were determined in liver tissue as well as activity of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, and catalase. In addition, inflammatory responses were assessed by measuring the expression of NF-κB (mRNA) and TNF-α (mRNA and protein). Histopathological analysis and measurement of liver enzymes (ALP, ALT, AST, and LDH in serum) were also done to determine hepatic injury. In liver, NTiO2 caused hepatic injury, redox perturbation, and reduction of antioxidant enzymes and elevation of inflammatory mediators, significantly. However, treatment with vitamins was able to significantly ameliorate these alterations. This study highlights the antioxidant and anti-inflammatory properties of vitamins A and E against toxicity of NTiO2 and poses the use of these vitamins to mitigate the toxic effects of this nanoparticles in NTiO2-contained products.

Undifferentiated Pleomorphic Sarcoma Presenting as Abdominal Pain with a Pulsatile Mass.

Malignant fibrous histiocytoma (MFH) is a rare tumor that mostly involves adults aged 50 to 70. The most common anatomic location is the lower extremities. MFH of the retroperitoneum usually manifests late in its course and may be initially mistaken with other more common diagnosis. Here, the authors describe a 60-year-old man that was brought to the emergency department with a chief complaint of periumbilical abdominal pain. Our patient presented with symptoms consistent with a symptomatic aortic aneurysm, but a mass was encountered during surgery. In such circumstances the diagnosis of malignant sarcoma must be kept in mind and attempts at full resection with tumor-free margins are necessary.

Ultra low-power transceiver with novel FSK modulation technique and efficient FSK-to-ASK demodulation.

Energy-efficient and high-data rate are desired in biomedical devices transceivers. A high-performance transmitter (Tx) and an ultra-low-power receiver (Rx) dedicated to medical implants communications operating at Industrial, Scientific and Medical (ISM) frequency band are presented. Tx benefits from a new efficient Frequency-Shift Keying (FSK) modulation technique which provides up to 20 Mb/s of data-rate and consumes only 0.084 nJ/b validated through fabrication. The receiver consists of an FSK-to-ASK conversion based receiver with OOK fully passive wake-up device (WuRx). This WuRx is battery less with energy harvesting technique which plays an important role in making the RF transceiver energy-efficient. The Rx is achieved with a reduced hardware architecture which does not use an accurate local oscillator, high-Q external inductor and I/Q signal path. The Rx shows -78 dBm sensitivity for 8 Mbps data rate while consuming 639 µW. The proposed circuits are implemented in IBM 0.13 µm CMOS technology with 1.2 V supply voltage.

Hospital waste management status in Iran: a case study in the teaching hospitals of Iran University of Medical Sciences.

Hospital waste materials pose a wide variety of health and safety hazards for patients and healthcare workers. Many of hospitals in Iran have neither a satisfactory waste disposal system nor a waste management and disposal policy. The main objective of this research was to investigate the solid waste management in the eight teaching hospitals of Iran University of Medical Sciences. In this cross-sectional study, the main stages of hospital waste management including generation, separation, collection, storage, and disposal of waste materials were assessed in these hospitals, located in Tehran city. The measurement was conducted through a questionnaire and direct observation by researchers. The data obtained was converted to a quantitative measure to evaluate the different management components. The results showed that the waste generation rate was 2.5 to 3.01 kg bed(-1) day(-1), which included 85 to 90% of domestic waste and 10 to 15% of infectious waste. The lack of separation between hazardous and non-hazardous waste, an absence of the necessary rules and regulations applying to the collection of waste from hospital wards and on-site transport to a temporary storage location, a lack of proper waste treatment, and disposal of hospital waste along with municipal garbage, were the main findings. In order to improve the existing conditions, some extensive research to assess the present situation in the hospitals of Iran, the compilation of rules and establishment of standards and effective training for the personnel are actions that are recommended.

A Jini-based solution for electronic prescriptions.

In most countries today, handwritten, paper-based medical prescriptions are the norm. While efforts have been made in the past and are being made at present to migrate toward electronic dispensation of prescriptions, these have generally omitted to incorporate ubiquitous computing technology in their proposed solutions. In this paper, we focus on this issue and describe a Jini-based prototypical solution for electronic prescriptions, which allows for their wireless transmission to in-range pharmacies and the augmentation of the service levels rendered to the user, with, for instance, information about queue lengths and estimated waiting times being provided to the patients. Clinical and user evaluation revealed that there were high levels of agreement as regards the prototype's effectiveness, ease of use, and usefulness.