Molecular and Clinicopathologic Characterization of Mismatch Repair-Deficient Endometrial Carcinoma Not Related to MLH1 Promoter Hypermethylation.

Universal tumor screening in endometrial carcinoma (EC) is increasingly adopted to identify individuals at risk of Lynch syndrome (LS). These cases involve mismatch repair-deficient (MMRd) EC without MLH1 promoter hypermethylation (PHM). LS is confirmed through the identification of germline MMR pathogenic variants (PV). In cases where these are not detected, emerging evidence highlights the significance of double-somatic MMR gene alterations as a sporadic cause of MMRd, alongside POLE/POLD1 exonuclease domain (EDM) PV leading to secondary MMR PV. Our understanding of the incidence of different MMRd EC origins not related to MLH1-PHM, their associations with clinicopathologic characteristics, and the prognostic implications remains limited. In a combined analysis of the PORTEC-1, -2, and -3 trials (n = 1254), 84 MMRd EC not related to MLH1-PHM were identified that successfully underwent paired tumor-normal tissue next-generation sequencing of the MMR and POLE/POLD1 genes. Among these, 37% were LS associated (LS-MMRd EC), 38% were due to double-somatic hits (DS-MMRd EC), and 25% remained unexplained. LS-MMRd EC exhibited higher rates of MSH6 (52% vs 19%) or PMS2 loss (29% vs 3%) than DS-MMRd EC, and exclusively showed MMR-deficient gland foci. DS-MMRd EC had higher rates of combined MSH2/MSH6 loss (47% vs 16%), loss of >2 MMR proteins (16% vs 3%), and somatic POLE-EDM PV (25% vs 3%) than LS-MMRd EC. Clinicopathologic characteristics, including age at tumor onset and prognosis, did not differ among the various groups. Our study validates the use of paired tumor-normal next-generation sequencing to identify definitive sporadic causes in MMRd EC unrelated to MLH1-PHM. MMR immunohistochemistry and POLE-EDM mutation status can aid in the differentiation between LS-MMRd EC and DS-MMRd EC. These findings emphasize the need for integrating tumor sequencing into LS diagnostics, along with clear interpretation guidelines, to improve clinical management. Although not impacting prognosis, confirmation of DS-MMRd EC may release patients and relatives from burdensome LS surveillance.

Examination of the Relationship Between Elective Surgical Patients' Methods for Coping With Stress and Sleeping Status the Night Before an Operation.

PURPOSE: This study was conducted to examine the relationship between elective surgical patients' methods for coping with stress and sleeping status the night before an operation. DESIGN: This research was a descriptive and correlational study. METHODS: The study was conducted between November 2016 and February 2017 with 132 patients who were waiting to undergo elective surgery in the surgery clinics of a university hospital. The data were collected using a personal information form, the Richards-Campbell Sleep Questionnaire (RCSQ), and the Ways of Coping Inventory (WOC). FINDINGS: This study indicated that the mean RCSQ score of the male patients and patients who were hospitalized at a cardiology clinic and experienced no situation that interrupted sleep the night before the operation was higher, and the difference was statistically significant (P < .05). Patients obtained a mean score of 46.31 ± 32.21 on the RCSQ. A positive significant relationship was found between the mean scores of the self-confident approach, optimistic approach, and receiving social support, which are subscales of the WOC, and the total mean score on the RCSQ (P < .01). A negative significant relationship was found between the mean scores of the helpless approach and the submissive approach subscales of the WOC, and the total mean score on the RCSQ (P < .01). CONCLUSIONS: The results of this study showed that the approaches that the patients waiting for elective surgery used to cope with stress affected their nocturnal sleep status.

Characterization of citrus pectin samples extracted under different conditions: influence of acid type and pH of extraction.

BACKGROUND AND AIMS: Pectin is a complex macromolecule, the fine structure of which is influenced by many factors. It is used as a gelling, thickening and emulsifying agent in a wide range of applications, from food to pharmaceutical products. Current industrial pectin extraction processes are based on fruit peel, a waste product from the juicing industry, in which thousands of tons of citrus are processed worldwide every year. This study examines how pectin components vary in relation to the plant source (orange, lemon, lime, grapefruit) and considers the influence of extraction conditions on the chemical and macromolecular characteristics of pectin samples. METHODS: Citrus peel (orange, lemon, lime and grapefruit) from a commercial supplier was used as raw material. Pectin samples were obtained on a bulk plant scale (kilograms; harsh nitric acid, mild nitric acid and harsh oxalic acid extraction) and on a laboratory scale (grams; mild oxalic acid extraction). Pectin composition (acidic and neutral sugars) and physicochemical properties (molar mass and intrinsic viscosity) were determined. KEY RESULTS: Oxalic acid extraction allowed the recovery of pectin samples of high molecular weight. Mild oxalic acid-extracted pectins were rich in long homogalacturonan stretches and contained rhamnogalacturonan I stretches with conserved side chains. Nitric acid-extracted pectins exhibited lower molecular weights and contained rhamnogalacturonan I stretches encompassing few and/or short side chains. Grapefruit pectin was found to have short side chains compared with orange, lime and lemon. Orange and grapefruit pectin samples were both particularly rich in rhamnogalacturonan I backbones. CONCLUSIONS: Structural, and hence macromolecular, variations within the different citrus pectin samples were mainly related to their rhamnogalacturonan I contents and integrity, and, to a lesser extent, to the length of their homogalacturonan domains.

The Impact of Parent-Based Support Programs on Neurodevelopmental Prognosis: Second-Year Results from a Newly Established Neurodevelopmental Follow-Up Unit in a Tertiary Hospital.

This study aims to assess the neurodevelopmental progress of high-risk infants 2 years post implementation of the Neurodevelopmental Follow-Up Unit (NFU) program at our hospital and explore implementation challenges for insights. Infants were assessed using the Hammersmith Infant Neurological Examination (HINE), The Alberta Infant Motor Scale (AIMS), and Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). A multidisciplinary team provided comprehensive parent education covering neurologic cues, postural advice, and developmental instructions in accordance with the children's assessment findings. In addition, a pediatric physical therapist provided motor development training emphasizing age-appropriate milestones and functional independence, while child development specialists addressed delays identified through BSID-III assessments. A total of 121 high-risk babies were enrolled during a 2-year period. Results revealed that 9 infants exhibited suboptimal HINE scores at 3-4 months, with only 2 maintaining suboptimal scores at 12-15 months. Similarly, 2 infants with suboptimal AIMS scores at 3-4 months reached normal values at 12-15 months. Comparable improvements were observed in BSID-III scores. While no correlation between HINE and AIMS scores was found at the 3-4-month mark, a significant correlation emerged between AIMS and HINE scores at 6-9 months (r = 0.643, P < .001) and 12-15 months (r = 0.820, P < .001). Encouraging early family education alongside regular monitoring of high-risk newborns appears to have a positive impact on their motor and cognitive development. Consideration of clinical recommendations, such as tailored interventions and periodic assessments, may contribute to optimizing developmental outcomes.

The effect of virtual reality on pain, anxiety, and fear during burn dressing in children: A randomized controlled study.

AIM AND OBJECTIVES: Virtual Reality (VR) can be used during painful procedures in children. This research was conducted to determine the effect of VR on the pain, anxiety, and fear levels experienced by patients during burn dressing. METHODS: A randomized between groups study design was used to test whether VR reduced pain, fear, and anxiety during burn wound cleaning. The experimental (VR group) (n = 33) and the control group (n = 32) were determined using the simple randomization method for the children participating in the study (n = 65). The data were collected using the Wong-Baker FACES Pain Rating Scale, Children's Fear Scale, and State- Trait Anxiety Inventory for Children. In addition, oxygen saturation and heart rate measurements were recorded before and after the procedure. RESULTS: Using a between groups t-test, burn injured children in the group that received virtual reality (M = 2.6, SD = 1.9, SE= 0.21) showed significantly less pain intensity during burn wound care than the No VR control group (M = 4.2, SD =1.0, SE= 0.19, t = -5.89, p < 0.005). Similarly, the VR group reported significantly lower fear during wound care (M= 2.24, SD = 1.1, SE=0.19) than the No VR control group (M=3.72, SD = 0.6, SE=0.10, t = 6.70, p < 0.005), and on a scale from 0 to 100, patients in the VR group showed significantly less anxiety (36.46, SD = 8.1, SE=1.40) than patients in the No VR group (M= 53.16, SD = 7.4, SE=1.35, t = 8.52, p < 0.005). Heart rate during wound care was significantly lower in the VR group (M=119.60, SD = 8.1, SE=1.40) than in the No VR control group (M=129.56, SD = 10.64, SE=1.88, t = -4.25, p < 0.005). However, no significant difference in Oxygen saturation was found, (VR = 97.03, SD = 0.90, SE= 0.17, vs. No VR = 96.94, SD = 0.29, SE=0.23, t = 0.326, p > 0.05). CONCLUSIONS: VR is an effective method in reducing pain, fear, and anxiety caused by burn dressing in children aged 7-12. The use of VR during burn dressing was determined to have positive results on some physical and psychological parameters.

Role of Preoperative Embolization in Surgical Management of Carotid Body Tumors: A Systematic Review and Meta-Analysis.

The objective of this study is to evaluate the effect of preoperative embolization on carotid body tumor resection. A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, Scopus, and Web of Science were screened for studies published between 2010 and 2022. Primary outcomes investigated were intraoperative blood loss, operative time, length of hospital stay, and perioperative complications such as transient ischemic attack (TIA)/stroke, vascular injury, and cranial nerve injury (CNI). A random effects model was used in cases where study heterogeneity was high. Overall, 25 studies were included in the systematic review, involving 1649 patients: 23 studies were eligible for meta-analysis. The incidence of vascular injury was significantly less in the preoperative embolization group (odds ratio (OR) = 0.60; 95% CI: 0.42-0.84; P = .003). There was no statistically significant difference between the two groups regarding intraoperative blood loss, operative time, length of hospital stay, incidence of TIA/stroke, and CNI. Subgroup analyses did not demonstrate significant difference between Shamblin I, II, and III subgroups regarding operative time. This meta-analysis found preoperative embolization to be significantly beneficial in reducing incidence of vascular injury.

Fucoidan Modulated Oxidative Stress and Caspase-3 mRNA Expression Induced by Sulfoxaflor in the Brain of Mice.

The current study aimed to investigate the role of fucoidan in the oxidative and apoptotic effects of sulfoxaflor, a neonicotinoid sulfoximine insecticide, in the brain of Swiss albino mice (Mus musculus). Sulfoxaflor and fucoidan were administered to mice at doses of 15 mg/kg/day (1/50 oral LD50) and 50 mg/kg/day, respectively, by oral gavage for 24 h or 7 days. The tGSH, TBARS and protein levels, and GPx, GR, and GST enzyme activities were determined by spectrophotometric methods. Caspase-3 gene expression level was determined by RT-PCR. Data analysis showed that brains of sulfoxaflor-treated mice exhibited higher TBARS levels; GPx, GR, and GST enzyme activities; and caspase-3 expression levels, as well as lower levels of tGSH. Co-administration of fucoidan and sulfoxaflor reduced the TBARS levels, increased tGSH levels, and increased GPx, GR, and GST enzyme activities. Fucoidan also decreased the sulfoxaflor-induced up-regulation of caspase-3 mRNA expression. Results of the present study showed that sulfoxaflor caused oxidative stress by inducing lipid peroxidation and altering GSH-dependent antioxidants in the brain of mice. In addition, sulfoxaflor may trigger apoptotic cell death shown by the up-regulation of caspase-3. Fucoidan treatment modulated all the aforementioned alterations in the brain of mice. It was concluded that fucoidan might have antioxidant effects that support the GSH-dependent antioxidant system and can play a modulator role in oxidative stress and caspase-3 expression in the brain of sulfoxaflor treated-mice.

Fucoidan Protects against Acute Sulfoxaflor-Induced Hematological/Biochemical Alterations and Oxidative Stress in Male Mice.

Fucoidan is a sulfated polysaccharide which can be found among a number of macroalgea species. It has a broad spectrum of biological activities including anti-oxidant, anti-tumor, immunoregulation, anti-viral and anti-coagulant. The current study was performed to investigate possible protective effects of fucoidan for sulfoxaflor-induced hematological/biochemical alterations and oxidative stress in the blood of male Swiss albino mice. For this purpose, sulfoxaflor was administered at a dose of 15 mg/kg/day (1/50 oral LD50), and fucoidan was administered at a dose of 50 mg/kg/day by oral gavage alone and combined for 24 h and 7 days. Hematological parameters (RBC, HGB, HCT, MCV, MCH, MCHC, Plt, WBC, Neu, Lym and Mon), serum biochemical parameters (AST, ALT, GGT, LDH, BUN, Cre and TBil), and serum oxidative stress/antioxidant markers (8-OHdG, MDA, POC and GSH) were analyzed. The results indicated that sulfoxaflor altered hematological and biochemical parameters and caused oxidative stress in mice; fucoidan ameliorated some hematological and biochemical parameters and exhibited a protective role as an antioxidant against sulfoxaflor-induced oxidative stress.