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1.
Biology (Basel) ; 13(7)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-39056667

ABSTRACT

BACKGROUND: The high incidence of metabolic syndrome in the elderly poses a significant challenge to the healthcare system, emphasizing the need for interventions tailored to geriatric patients. Given the limited focus on females in previous studies, this research aimed to evaluate the effects of dietary curcumin on obesity and NAFLD outcomes in naturally aged (18-month-old) female mice. METHODS: Female C57BL/6 mice aged 18 months were fed a normal chow diet (NCD) and a HFHSD, with or without curcumin (0.4% w/w), for an 8-week period. Parameters included food intake, body weight, insulin tolerance test (ITT), glucose tolerance test (GTT), percentage fat mass, hepatic triglyceride, and cholesterol levels, and a histological examination for NAFLD detection, qPCR, and immunoblotting analyses were performed. RESULTS: The cumulative body weight gain after 8 weeks in the aged female mice supplemented with curcumin and fed an HFHSD was significantly lower (10.84 ± 1.09 g) compared to those fed a HFHSD alone (15.28 ± 1.26 g). Curcumin supplementation also resulted in reduced total body fat (HFHSD group 50.83 ± 1.71% vs. HFHSD+CUR 41.46 ± 3.21%), decreased epidydimal fat mass (HFHSD: 3.79 ± 0.29 g vs. HFHSD+CUR: 2.66 ± 0.30 g), and repaired adipogenic signaling in the white adipose tissue. Furthermore, curcumin lowered triglyceride and cholesterol deposition in the liver, preventing hepatic steatosis and improving hepatic insulin sensitivity. CONCLUSIONS: Curcumin demonstrates the ability to ameliorate the deleterious effects of HFHSD in aged female mice by reducing body fat composition, modulating adipogenic signaling in the white adipose tissue, and improving insulin homeostasis and non-alcoholic fatty deposition in the liver.

2.
Cancer Res Treat ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39026430

ABSTRACT

Accurate detection of homologous recombination deficiency (HRD) in cancer patients is paramount in clinical applications, as HRD confers sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors. With the advances in genome sequencing technology, mutational profiling on a genome-wide scale has become readily accessible, and our knowledge of the genomic consequences of HRD has been greatly expanded and refined. Here, we review the recent advances in HRD detection methods. We examine the copy number and structural alterations that often accompany the genome instability that results from HRD, describe the advantages of mutational signature-based methods that do not rely on specific gene mutations, and review some of the existing algorithms used for HRD detection. We also discuss the choice of sequencing platforms (panel, exome, or whole-genome) and catalog the HRD detection assays used in key PARP inhibitor trials.

3.
Ann Surg Oncol ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38969851

ABSTRACT

BACKGROUND: Current guidelines recommend against the use of routine imaging tests to detect distant metastasis in asymptomatic breast cancer patients. However, recent advancements in effective therapeutics and diagnostic accuracy have raised the need to reassess the clinical efficacy of intensive metastasis surveillance. We report the results of a multicenter retrospective study to investigate the association between intensive imaging studies and survival outcomes. PATIENTS AND METHODS: We retrospectively reviewed the data of 4130 patients who underwent surgery from 11 hospitals in Korea between January 2010 and December 2011. Patients were divided into two groups on the basis of the intensity of metastasis imaging studies during their disease-free period. The types and intervals of the imaging studies were based on each physician's decisions. RESULTS: High-intensive screening showed a shorter distant metastasis-free survival [p < 0.001, hazard ratio (HR) 1.62; 95% confidence interval (CI) 1.29-2.04], especially for patients in whom bone or lung was the first site of metastasis. With a median follow-up period of 110.0 months, the 5-year breast cancer-specific survival (BCSS) rate was 96.5%. The high-intensity screening group showed significantly poorer BCSS compared with the low-intensity screening group (p < 0.001, HR 3.13; 95% CI 2.32-4.21). However, both multivariable analysis and propensity score matching analysis showed no significant association between the screening intensity and BCSS. CONCLUSIONS: Frequent imaging studies to detect distant metastasis were associated with earlier detection of distant metastasis, especially for lung and bone metastasis. However, intensive surveillance showed no apparent association with BCSS despite the use of currently available treatments.

4.
Cancer Res Treat ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38965924

ABSTRACT

Purpose: Proximal gastrectomy is an alternative to total gastrectomy (TG) for early gastric cancer (EGC) treatment in the upper stomach. However, its benefits in terms of perioperative and long-term outcomes remain controversial. The aim of this study was to compare the perioperative, body compositional, nutritional, and survival outcomes of patients undergoing proximal gastrectomy with double-tract reconstruction (PG-DTR) and TG for pathological stage I gastric cancer in upper stomach. Materials and Methods: The study included 506 patients who underwent gastrectomy for pathological stage I gastric cancer in the upper stomach between 2015 and 2019. Clinicopathological, perioperative, body compositional, nutritional, and survival outcomes were compared between the PG-DTR and TG groups. Results: The PG-DTR and TG groups included 197 (38.9%) and 309 (61.1%) patients, respectively. The PG-DTR group had a lower rate of early complications (p=0.041), lower diagnosis rate of anemia and vitamin B12 deficiency (all p<0.001), and lower replacement rate of iron and vitamin B12 compared to TG group (all p<0.001). The PG-DTR group showed reduced incidence of sarcopenia at 6-months postoperatively, preserved higher amount of visceral fat after surgery (p=0.032 and p=0.040, respectively), and showed a higher hemoglobin level (p=0.007). Oncologic outcomes were comparable between the groups. Conclusion: The PG-DTR for EGC located in the upper stomach offered advantages of fewer complications, lower incidence of anemia and vitamin B12 deficiency, less decrease in visceral fat volume, and similar survival compared to TG. Consequently, PG-DTR may be considered a superior alternative treatment option to TG.

5.
J Anim Sci Technol ; 66(3): 587-602, 2024 May.
Article in English | MEDLINE | ID: mdl-38975577

ABSTRACT

This research was conducted to study the effects of organic selenium (Se) supplements at different levels on pork loin quality during storage. Fifteen pork loins were procured randomly from three groups, Con (fed basal diet), Se15 (fed 0.15 ppm organic Se along with 0.10 ppm inorganic Se), and Se45 (fed 0.45 ppm organic Se along with 0.10 ppm inorganic Se). Each sample was analyzed for Se contents, antioxidant properties (glutathione peroxidase [GPx] activity, 2,2'-azinobis-[3-ethylbenzothiazoline-6-sulfonic acid] [ABTS] and 2,2-diphenyl-1-picrylhydrazyl [DPPH] radical scavenging activities, 2-thiobarbituric acid reactive substances), physicochemical properties (water holding capacity, pH, color), and metabolomic analysis during 14-day storage period. Se45-supplemented group showed significantly higher Se contents and GPx activity than the other groups throughout the storage period. However, other antioxidant properties were not significantly affected by Se supplementation. Selenium supplementation did not have an adverse impact on physicochemical properties. Nuclear Magnetic Resonance-based metabolomic analysis indicated that the selenium supply conditions were insufficient to induce metabolic change. These results suggest that organic Se (0.15 and 0.45 ppm) can accumulate high Se content in pork loins without compromising quality.

6.
Article in English | MEDLINE | ID: mdl-38997400

ABSTRACT

Reduced-toxicity conditioning (RTC) regimens aim to mitigate regimen-related toxicity while maintaining anti-leukemic efficacy in allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed outcomes of RTC regimens utilizing melphalan versus intravenous busulfan combined with fludarabine in adult acute lymphoblastic leukemia (ALL) patients. A retrospective analysis was conducted with 149 consecutive adult ALL patients (median age 51, range 18-60) in remission undergoing allo-HSCT. Patients received either fludarabine 150 mg/BSA plus 2 days of melphalan 70 mg/BSA (FM140, n = 76) from 2009 to 2015 or fludarabine plus 3 days of busulfan 3.2 mg/kg (FB9.6, n = 73) from 2016 to 2021. At 5 years post-HSCT, FM140 demonstrated superior disease-free survival (53.4% vs. 30.5%, p = 0.007) and lower cumulative relapse (27.4% vs. 46.8%, p = 0.026) than FB9.6. Five-year overall survival and non-relapse mortality did not significantly differ. FM140 exhibited a higher incidence of acute graft-versus-host disease (GVHD) grades II-IV (49.3% vs. 30.3%, p = 0.016), though rates of acute GVHD grades III-IV and chronic GVHD were similar. Multivariate analysis identified Philadelphia chromosome and minimal residual disease positive status, and FB9.6 conditioning as predictors of increased relapse and poorer disease-free survival. FM140 RTC regimen displayed significantly reduced relapse and superior disease-free survival compared to FB9.6 in ALL patients undergoing allo-HSCT, highlighting its current clinical utility.

7.
Biomed Pharmacother ; 177: 117062, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38971009

ABSTRACT

Smoking remains a significant health problem in patients with type 2 diabetes mellitus. This study compared intracellular Ca2+ ([Ca2+]i) in microglia, neurons, and astrocytes in the presence of high glucose (HG) and nicotine and evaluated the effects of Lavandula angustifolia Mill. essential oil (LEO) on this process. [Ca2+]i concentrations were measured by monitoring the fluorescence of Fura-2 acetoxymethyl ester. Treatment with HG and nicotine significantly increased [Ca2+]i in both microglia and neurons through Ca2+ influx from extracellular sources. This increased Ca2+ influx in microglia, however, was significantly reduced by LEO, an effect partially inhibited by the Na+/Ca2+ exchanger (NCX) inhibitor Ni2+. Ca2+ influx in neuron-like cells pretreated with HG plus nicotine was also significantly decreased by LEO, an effect partially inhibited by the L-type Ca2+ channel blocker nifedipine and the T-type Ca2+ channel blocker mibefradil. LEO or a two-fold increase in the applied number of astrocytes attenuated Ca2+ influx caused by high glucose and nicotine in the mixed cells of the microglia, neuron-like cells and astrocytes. These findings suggest that LEO can regulate HG and nicotine-induced Ca2+ influx into microglia and neurons through two distinct mechanisms.


Subject(s)
Calcium , Glucose , Lavandula , Microglia , Neurons , Nicotine , Nicotine/pharmacology , Glucose/metabolism , Microglia/drug effects , Microglia/metabolism , Calcium/metabolism , Animals , Neurons/drug effects , Neurons/metabolism , Oils, Volatile/pharmacology , Astrocytes/drug effects , Astrocytes/metabolism , Rats , Calcium Channel Blockers/pharmacology , Cells, Cultured
8.
PLoS One ; 19(6): e0304875, 2024.
Article in English | MEDLINE | ID: mdl-38833438

ABSTRACT

Previous studies have shown that fetal abdominal obesity (FAO) was already observed at the time of gestational diabetes mellitus (GDM) diagnosis and persisted until delivery despite management in older and/or obese women. In this study, we investigated whether fetuses of women with milder hyperglycemia than GDM have accelerated abdominal growth, leading to adverse pregnancy outcomes. We retrospectively reviewed the medical records of 7,569 singleton pregnant women who were universally screened using a 50-g glucose challenge test (GCT) and underwent a 3-h 100-g oral glucose tolerance test (OGTT) if GCT result was ≥140mg/dL. GDM, one value abnormality (OVA), and normal glucose tolerance (NGT, NGT1: GCT negative, NGT2: GCT positive & OGTT negative) were diagnosed using Carpenter-Coustan criteria. With fetal biometry data measured simultaneously with 50-g GCT, relative fetal abdominal overgrowth was investigated by assessing the fetal abdominal overgrowth ratios (FAORs) of the ultrasonographically estimated gestational age (GA) of abdominal circumference(AC) per actual GA by the last menstruation period(LMP), biparietal diameter(BPD) or femur length(FL), respectively. FAO was defined as FAOR ≥90th percentile The FAORs of GA-AC/GA-LMP and GA-AC/GA-BPD were significantly higher in OVA subjects compared to NGT subjects but not in NGT2 subjects. Although the frequency of FAO in OVA (12.1%) was between that of NGT (9.6%) and GDM (18.3%) without statistically significant difference, the prevalence of large for gestational age at birth and primary cesarean delivery rates were significantly higher in OVA (9.8% and 29.7%) than in NGT (5.1% and 21.5%, p<0.05). Particularly, among OVA subjects with FAO, the prevalence (33.3% and 66.7%) was significantly higher than in those without FAO (9.7% and 24.2%, p<0.05). The degree of fetal abdominal growth acceleration in OVA subjects was intermediate between that of NGT and GDM subjects. OVA subjects with FAO at the time of GDM diagnosis were strongly associated with adverse pregnancy outcomes.


Subject(s)
Diabetes, Gestational , Glucose Tolerance Test , Obesity, Abdominal , Humans , Female , Pregnancy , Diabetes, Gestational/diagnosis , Obesity, Abdominal/diagnosis , Adult , Retrospective Studies , Gestational Age , Pregnancy Outcome , Ultrasonography, Prenatal
9.
Article in English | MEDLINE | ID: mdl-38863389

ABSTRACT

BACKGROUND: Antimicrobial resistance (AMR), driven by inappropriate and overuse of antibiotics, poses a significant threat, especially to patients with acute leukaemia. OBJECTIVES: To evaluate the impact of antimicrobial stewardship programmes (ASPs) on antibiotic use and analyse temporal changes in bloodstream infections (BSI) caused by AMR organisms. METHODS: We performed a retrospective, interventional, longitudinal cohort study spanning an 11-year period. ASPs included optimizing antibiotic use, enhancing tracking and reporting systems and delineating leadership and accountability. A segmented regression model of interrupted time series was used to evaluate the trend of antibiotic consumption and BSI with AMR organisms after the interventions. RESULTS: A total of 3296 BSI episodes with 454 419 days of therapy (DOT) from 7754 patients were obtained. ASPs were significantly associated with an immediate reduction [-70.03 DOT/1000 patient-days (PD), P = 0.036] and a decreasing trend (-11.65 DOT/1000 PD per quarter, P < 0.001) in overall antibiotic use. The increasing incidence of BSI with AMR before ASP intervention was notably curbed and revealed a decreasing trend (slope change: -0.06 BSI/1000 PD per quarter, P = 0.002). The decreasing trend was more significant for Enterobacterales: ciprofloxacin-resistant and ESBL-producing isolates showed a slope change of -0.06 BSI/1000 PD and -0.08 BSI/1000 PD per quarter, respectively (all P < 0.05). However, Pseudomonas aeruginosa BSI increased. CONCLUSIONS: Multidimensional ASPs effectively reduced both the immediate and trends in overall antibiotic usage even in patients with acute leukaemia. Additionally, there was a notable decrease in the incidence of BSI caused by AMR organisms, particularly among Enterobacterales.

10.
J Clin Ultrasound ; 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38864446

ABSTRACT

Primary inguinal hernia is a common pediatric surgical condition with an incidence of 1%-4%, which is higher in male or premature newborns. It is characterized by the protrusion of abdominal contents through inguinal canal in newborns. However, prenatal fetal inguinal hernia is a rare condition because the pressure of amniotic fluid is similar to intra-abdominal pressure. Only 19 English publications were found with 21 reported cases until now. We report belatedly discovered inguinoscrotal hernia at 38+0 weeks' gestation. Usually, the fetal testicular descent begins from 24 to 25 weeks' gestation, and it is found after 32 weeks of gestational age in 97% of the fetuses. Therefore, it is necessary to get into the habit of checking fetal testicles during routine US after at least 32 weeks of gestational age.

11.
Sci Rep ; 14(1): 14390, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38909074

ABSTRACT

Recent advances in deep learning have led to a surge in computer vision research, including the recognition and classification of human behavior in video data. However, most studies have focused on recognizing individual behaviors, whereas recognizing crowd behavior remains a complex problem because of the large number of interactions and similar behaviors among individuals or crowds in video surveillance systems. To solve this problem, we propose a three-dimensional atrous inception module (3D-AIM) network, which is a crowd behavior classification model that uses atrous convolution to explore interactions between individuals or crowds. The 3D-AIM network is a 3D convolutional neural network that can use receptive fields of various sizes to effectively identify specific features that determine crowd behavior. To further improve the accuracy of the 3D-AIM network, we introduced a new loss function called the separation loss function. This loss function focuses the 3D-AIM network more on the features that distinguish one type of crowd behavior from another, thereby enabling a more precise classification. Finally, we demonstrate that the proposed model outperforms existing human behavior classification models in terms of accurately classifying crowd behaviors. These results suggest that the 3D-AIM network with a separation loss function can be valuable for understanding complex crowd behavior in video surveillance systems.

12.
ACS Nano ; 18(27): 17557-17569, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38913718

ABSTRACT

Several fabrication methods have been developed for label-free detection in various fields. However, fabricating high-density and highly ordered nanoscale architectures by using soluble processes remains a challenge. Herein, we report a biosensing platform that integrates deep learning with surface-enhanced Raman scattering (SERS), featuring large-area, close-packed three-dimensional (3D) architectures of molybdenum disulfide (MoS2)-assisted gold nanoparticles (AuNPs) for the on-site screening of coronavirus disease (COVID-19) using human tears. Some AuNPs are spontaneously synthesized without a reducing agent because the electrons induced on the semiconductor surface reduce gold ions when the Fermi level of MoS2 and the gold electrolyte reach equilibrium. With the addition of polyvinylpyrrolidone, a two-dimensional large-area MoS2 layer assisted in the formation of close-packed 3D multistacked AuNP structures, resembling electroless plating. This platform, with a convolutional neural network-based deep learning model, achieved outstanding SERS performance at subterascale levels despite the microlevel irradiation power and millisecond-level acquisition time and accurately assessed susceptibility to COVID-19. These results suggest that our platform has the potential for rapid, low-damage, and high-throughput label-free detection of exceedingly low analyte concentrations.


Subject(s)
Deep Learning , Disulfides , Gold , Metal Nanoparticles , Molybdenum , Spectrum Analysis, Raman , Gold/chemistry , Molybdenum/chemistry , Spectrum Analysis, Raman/methods , Disulfides/chemistry , Metal Nanoparticles/chemistry , Humans , Surface Properties , COVID-19/virology , Biosensing Techniques/methods , SARS-CoV-2/isolation & purification , Particle Size
13.
Curr Issues Mol Biol ; 46(6): 6100-6111, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38921035

ABSTRACT

This study examines the synergistic interaction between the immunomodulatory functions of lactic acid bacteria postbiotics and the anti-inflammatory properties of Smilax china L. extract through a combined fermentation process. Using atopic dermatitis (AD) as a model, characterized by an immune imbalance that leads to skin inflammation, we developed a fermented product, MB-2006, and compared its effects to those of the heat-killed probiotics Lactobacillus acidophilus (LAC) and Lactobacillus rhamnosus (LRH). Our experiments focused on elucidating the mechanism of action of MB-2006 in AD-like HaCaT keratinocyte cells, particularly its impact on the NF-κB pathway, a pivotal regulator of inflammation. MB-2006 proved more effective in reducing inflammation markers, such as IL-4 and thymic stromal lymphopoietin (TSLP), and in inhibiting NF-κB activation compared to LAC and LRH. Significantly, MB-2006 also reduced the expression of thymus- and activation-regulated chemokine (TARC), highlighting a synergistic effect that enhances its therapeutic potential. These results suggest that the combined fermentation of Smilax china L. extract with lactic acid bacteria enhanced both the anti-inflammatory and immunomodulatory effects, presenting a promising integrative approach to treating conditions like AD. Further studies are needed to validate these results in clinical settings and fully explore the potential of this synergistic fermentation process.

14.
Medicine (Baltimore) ; 103(26): e38694, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38941432

ABSTRACT

Schizophrenia (SPR) is the most devastating mental illness that causes severe deterioration in social and occupational functioning, but, the etiology remains unknown. The objective of this study is to explore the genetic underpinnings of novelty seeking behavior in schizophrenic family within the Korean population. By conducting a family-based genome-wide association study, we aim to identify potential genetic markers and variations associated with novelty seeking traits in the context of SPR. We have recruited 27 probands (with SPR) with their parents and siblings whenever possible. DNA was extracted from blood sampling of 58 individuals in 27 families and analyzed in an Illumina core exome single nucleotide polymorphism (SNP) array. A family-based association test (qFAM) was used to derive SNP association values across all chromosomes. Although none of the final 800,000 SNPs reached the genome-wide significant threshold of 8.45 × 10-7, the most significant 4 SNPs were within the 10-5 to 10-7. This study identifies genetic associations between novelty seeking behavior and SPR within families. RAPGEF5 emerges as a significant gene, along with other neuropsychiatric-related genes. Noteworthy genes like DRD4 and COMT did not show associations, possibly due to the focus on schizophrenic family. While shedding light on this complex relationship, larger studies are needed for robust conclusions and deeper mechanistic insights.


Subject(s)
Exploratory Behavior , Genome-Wide Association Study , Polymorphism, Single Nucleotide , Schizophrenia , Humans , Schizophrenia/genetics , Male , Female , Republic of Korea/epidemiology , Pilot Projects , Adult , Middle Aged , Genetic Predisposition to Disease , Young Adult
15.
Poult Sci ; 103(8): 103886, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38878747

ABSTRACT

The objective of this study was to determine the effects of dietary available phosphorus (P) levels and dietary phytase added into the very low-P diet on the performance, mineral balance, odor emission, and stress responses in growing pullets and laying hens during 13 to 32 wk of age. One hundred sixty-eight pullets (Hy-Line Brown) were randomly assigned into 1 of 4 dietary treatments with 7 replicates of 6 birds each. Experimental diets were formulated to contain 3 graded P levels at 0.25, 0.35, and 0.45% during 13 to 15 wk (phase 1), 0.25, 0.35, and 0.45% during 16 to 18 wk (phase 2), and 0.20, 0.30, and 0.40% during 19 to 32 wk (phase 3). In addition, dietary phytase (500 FTU/kg matrix values) was added into the very low-P diets (0.20% during 13-15 wk, 0.25% during 16-18 wk, and 0.20% during 19-32 wk) to meet the nutritional adequacy with standard P diets. In all phases, decreasing dietary P levels did not affect (P > 0.05) growth, laying performance, and egg qualities. Decreasing dietary P levels linearly increased the relative duodenal and oviduct weights (P < 0.05), and quadratically increased the relative ovary weight in pullets (P = 0.016). Dietary phytase lowered (P = 0.021) the relative duodenal weight compared with the very low-P diet. Tibia breaking strength and tibia Mg contents in pullets were linearly lowered (P < 0.05) as dietary P levels decreased. Dietary phytase tended to increase (P = 0.091) tibia breaking strength and significantly increased (P = 0.025) tibia Mg content compared with the very low-P diet. Dietary P levels and dietary phytase affected (P < 0.05) ileal crypt depth and ileal villus height: crypt depth ratio in pullets. Decreasing dietary P levels linearly decreased (P < 0.01) crude fat digestibility and P excretion in both pullets and laying hens. Dietary phytase reversed (P < 0.05) the very low-P diet-mediated decrease of crude fat digestibility in pullets and laying hens. Dietary P levels and dietary phytase affected (P < 0.05) odor emission including ammonia in pullets and total volatile fatty acids in laying hens. Finally, lowering dietary P levels increased (P < 0.01) yolk corticosterone concentrations and the increased corticosterone concentration by the very low-P diet was reversed by dietary phytase. Collectively, our study shows that decreasing dietary P levels induced nutritional and physiological responses in pullets and laying hens and these P-mediated negative effects were mitigated by dietary phytase.


Subject(s)
6-Phytase , Animal Feed , Animal Nutritional Physiological Phenomena , Chickens , Diet , Dietary Supplements , Phosphorus, Dietary , Random Allocation , Animals , 6-Phytase/administration & dosage , 6-Phytase/metabolism , Chickens/physiology , Chickens/growth & development , Female , Diet/veterinary , Animal Feed/analysis , Phosphorus, Dietary/metabolism , Phosphorus, Dietary/administration & dosage , Animal Nutritional Physiological Phenomena/drug effects , Dietary Supplements/analysis , Dose-Response Relationship, Drug , Phosphorus/metabolism
16.
Article in English | MEDLINE | ID: mdl-38713398

ABSTRACT

PURPOSE: Although leukemic retinopathy accounts for 80% of ocular complications in acute leukemia, its pathogenesis remains unclear. To evaluate changes in retinal and choroicapillaris and structural parameters in patients with acute leukemia, we analyzed the correlation between vascular perfusion metrics and laboratory parameters and assessed the changes after hematopoietic stem cell transplantation (HSCT). METHODS: Herein, 104 eyes of 52 patients aged 18 and above with acute leukemia were enrolled. 80 eyes of 40 healthy patients were recruited as control participants. All participants underwent optical coherence tomography (OCT) and OCT angiography (OCTA) at baseline. RESULTS: Patients with acute leukemia had a significantly thicker ganglion cell-inner plexiform layer (GCIPL) and lower circularity index than the control participants. Post-HSCT perfusion metrics did not differ significantly, but parafoveal thickness decreased significantly. During the active phase of acute leukemia, lower platelet levels were associated with significant GCIPL thickening and increased foveal avascular zone and perimeter. D-dimer levels positively correlated with GCIPL thickness. CONCLUSION: Patients with acute leukemia had subclinical retinal microvascular deficits on OCTA and GCIPL thickening on OCT, possibly associated with bone marrow function. GCIPL thickness may indicate acute ischemia in such patients. Further studies must elucidate their clinical and prognostic significance.

17.
Front Oncol ; 14: 1351778, 2024.
Article in English | MEDLINE | ID: mdl-38725623

ABSTRACT

Objective: Effective functional biomarkers that can be readily used in clinical practice to predict poly(ADP-ribose) polymerase inhibitor (PARPi) sensitivity are lacking. With the widespread adoption of PARPi maintenance therapy in ovarian cancer, particularly in patients with BRCA mutation or HR deficiencies, accurately identifying de novo or acquired resistance to PARPi has become critical in clinical practice. We investigated RAD51 immunohistochemistry (IHC) as a functional biomarker for predicting PARPi sensitivity in ovarian cancer. Methods: Ovarian cancer patients who had received PARPi and had archival tissue samples prior to PARPi exposure ("pre-PARPi") and/or after progression on PARPi ("post-PARPi") were selected. RAD51 IHC expression was semi-quantitatively evaluated using the H-score in geminin (a G2/S phase marker)- and γH2AX (a DNA damage marker)-positive tissues. A RAD51 H-score of 20 was used as the cutoff value. Results: In total, 72 samples from 56 patients were analyzed. The median RAD51 H-score was 20 (range: 0-90) overall, 10 (0-190) in pre-PARPi samples (n = 34), and 25 (1-170) in post-PARPi samples (n = 19). Among patients with BRCA mutations, RAD51-low patients had better progression-free survival (PFS) after PARPi treatment than RAD51-high patients (P = 0.029). No difference was found in PFS with respect to the genomic scar score (P = 0.930). Analysis of matched pre- and post-PARPi samples collected from 15 patients indicated an increase in the RAD51 H-score upon progression on PARPi, particularly among pre-PARPi low-RAD51-expressing patients. Conclusion: RAD51 is a potential functional IHC biomarker of de novo and acquired PARPi resistance in BRCA-mutated ovarian cancer and can be used to fine-tune ovarian cancer treatment.

18.
J Pediatr Endocrinol Metab ; 37(6): 553-558, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38754024

ABSTRACT

OBJECTIVES: Osteoporosis poses a growing public health challenge worldwide. While calcium and vitamin D may influence bone mineral density (BMD), the effect of sodium (Na) intake, particularly in pediatrics, remains unexplored. This study aimed to evaluate the relationship between urinary Na excretion and BMD in a Korean pediatric population. METHODS: A total of 2,018 participants (1,084 males and 934 females) aged 10-18 years were included from the data obtained from Korea National Health and Nutrition Examination Survey V (2010-2011). RESULTS: Daily Na intake was about 4,560 mg and 3,600 mg in boys and girls, respectively. The mean intake of Na per day was positively correlated with the increment of urine Na/Cr ratio quartile (p<0.001). The BMD z-score [lumbar spine (LS), femur neck (FN), and whole body except head (WB)] in the group with high Na/Cr ratio (4th quartile, 4Q) was significantly less than in those with low Na/Cr ratio (1st quartile, 1Q) (p<0.001). Moreover, the LS (p=0.028), FN (p=0.002) and WB (p=0.056) in the 4Q group showed 2.0 times, 2.8 times, and 1.9 times greater risk of low BMD z-scores than in the 1Q group, even after adjusting for other confounding factors, such as age, sex, BMI, vitamin D, moderate activity, and household incomes. CONCLUSIONS: Our findings suggest a strong negative association between urine Na excretion and BMD among Korean children and adolescents. The results underscore the importance of public health interventions targeting Na intake. Further longitudinal studies are recommended to clarify the long-term effects of Na on bone health in younger populations.


Subject(s)
Bone Density , Nutrition Surveys , Sodium , Humans , Male , Female , Child , Adolescent , Sodium/urine , Republic of Korea/epidemiology , Osteoporosis/urine , Osteoporosis/epidemiology , Follow-Up Studies , Cross-Sectional Studies , Prognosis
19.
Endocrinol Metab (Seoul) ; 39(3): 450-460, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38798239

ABSTRACT

BACKGRUOUND: The diagnostic accuracy of preoperative radiologic findings in predicting the tumor characteristics and clinical outcomes of papillary thyroid microcarcinoma (PTMC) was evaluated across all risk groups. METHODS: In total, 939 PTMC patients, comprising both low-risk and non-low-risk groups, who underwent surgery were enrolled. The preoperative tumor size and lymph node metastasis (LNM) were evaluated by ultrasonography within 6 months before surgery and compared with the postoperative pathologic findings. Discrepancies between the preoperative and postoperative tumor sizes were analyzed, and clinical outcomes were assessed. RESULTS: The agreement rate between radiological and pathological tumor size was approximately 60%. Significant discrepancies were noted, including an increase in tumor size in 24.3% of cases. Notably, in 10.8% of patients, the postoperative tumor size exceeded 1 cm, despite being initially classified as 0.5 to 1.0 cm based on preoperative imaging. A postoperative tumor size >1 cm was associated with aggressive pathologic factors such as multiplicity, microscopic extrathyroidal extension, and LNM, as well as a higher risk of distant metastasis. In 30.1% of patients, LNM was diagnosed after surgery despite not being suspected before the procedure. This group was characterized by smaller metastatic foci and lower risks of distant metastasis or recurrence than patients with LNM detected both before and after surgery. CONCLUSION: Among all risk groups of PTMCs, a subset showed an increase in tumor size, reaching 1 cm after surgery. These cases require special consideration due to their association with adverse clinical outcomes, including an elevated risk of distant metastasis.


Subject(s)
Carcinoma, Papillary , Thyroid Neoplasms , Humans , Thyroid Neoplasms/pathology , Thyroid Neoplasms/surgery , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/diagnosis , Female , Male , Middle Aged , Carcinoma, Papillary/surgery , Carcinoma, Papillary/pathology , Carcinoma, Papillary/diagnostic imaging , Adult , Ultrasonography , Lymphatic Metastasis , Aged , Thyroidectomy , Postoperative Period , Preoperative Period , Retrospective Studies , Tumor Burden , Prognosis , Treatment Outcome
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