Effect of body mass index on post-treatment oral function in patients with oral cancer: a cross-sectional study.

This single-center cross-sectional study used sequential sampling to examine the influence of body mass index (BMI) on oral function after oral cancer treatment. Patients who completed primary oral cancer treatment between September 2019 and March 2023 (102 patients, 74 male [72.5%] and 28 female [27.5%]; mean age, 69.6 years) were analyzed. Patient background data were collected from electronic medical records. Post-treatment oral function measurements were conducted on all patients using six assessment tools. Statistical analysis was conducted using Pearson's correlation coefficient, one-way analysis of variance, the Jonckheere-Terpstra test, and multiple linear regression. Pre-treatment BMI showed a statistically significant relationship with postoperative oral function, particularly tongue pressure (P = 0.01). While the mean values of the groups showed no significant differences, the Jonckheere-Terpstra test revealed a statistically significant trend toward a stepwise increase in tongue pressure for each BMI group (P = 0.03). Multiple linear regression analysis revealed a statistically significant correlation between tongue pressure and pre-treatment BMI (P < 0.05). Pre-treatment BMI was significantly associated with tongue pressure. Since BMI is a variable factor that can be controlled by nutritional therapy even before treatment, nutritional intervention, weight control, and treatment strategies including reconstructive interventions to maintain tongue pressure may be important in oral cancer treatment.

Estimating copy number to determine BRCA2 deletion status and to expect prognosis in localized prostate cancer.

BACKGROUND: The significance of BRCA alterations has been implicated in the development of metastatic castration-resistant prostate cancer (PC). The details of the frequency and significance of BRCA alterations in localized PC remain unknown. In this study, we investigated the frequency and clinical significance of BRCA alterations in localized PCs using an in-house next-generation sequencer (NGS) system. METHODS: DNA was extracted from formalin-fixed paraffin-embedded tissues of surgical specimens from 126 patients with clinically localized PC who underwent radical prostatectomy. The mutation information of 164 cancer genes was analyzed using the PleSSision-Rapid test. Both copy number (CN) variation and loss of heterozygosity of various genes, such as BRCA1 and BRCA2, were estimated and reported. RESULTS: Next-generation sequencer analyses revealed that the BRCA2 CN was decreased in 17 patients (13.5%) and the BRCA1 CN in six (4.8%) patients. NGS-based CN values were shown to be highly correlated with droplet digital PCR-based CN values. Tissue-specific BRCA expression investigated using the Human Protein Atlas showed that the decreased CN of BRCA2, but not BRCA1, is responsible for the decreased BRCA activity in PC. Ten of the 22 patients with decreased BRCA2 CN were presumed to have somatic heterozygous deletion. There were no observed associations between the heterozygous deletion of BRCA2 and various clinicopathological parameters. Furthermore, three of 10 patients developed biochemical recurrence within 3 months after surgery. Multivariate analyses revealed that the initial prostate-specific antigen levels and BRCA2 CN were independent factors for biochemical recurrence. CONCLUSION: Our results suggest that a decrease in BRCA2 CN may be used as a biomarker for predicting recurrence after surgery in localized PC. Early screening for somatic alterations in BRCA2 using NGS may help to broadly predict the risk of PC progression.

Oral Dysfunction in Patients with Oral Cancer Could Occur Before Treatment and Require Early Nutritional Improvement: A Cross-Sectional Study.

Patients with oral cancer have poor nutritional status before treatment. However, there have been no reports of the detailed evaluation of preoperative oral function in patients with oral squamous cell carcinoma (OSCC). Therefore, this study aimed to evaluate the preoperative oral function of patients with OSCC and examine the relationship with nutritional status. Oral function measurements (microorganisms, oral dryness, occlusal force, tongue pressure, masticatory function, Eating Assessment Tool, and Postoperative Oral Dysfunction Scale) and Mini Nutritional Assessment-Short Form (MNA-SF) data were collected from 51 patients with OSCC (men: 37, women: 14, mean age: 72.1 years) who visited the Shimane University Hospital, Department of Oral and Maxillofacial Surgery, from September 2019 to September 2021. The tongue was the most prevalent primary gingiva site [22 patients (43.1%)], and 36 patients (70.6%) had advanced cancer. Comparisons between nutritional status and each related factor revealed significant differences in the number of individuals in the household, cancer stage, presence of pulmonary disease, number of teeth, microorganisms (grade), and masticatory function (mg/dL) (p < 0.05). Multiple regression analysis using the total MNA-SF score as the dependent variable with adjustment for confounding factors showed significant association between oral dryness and tongue pressure (p < 0.05). No significant association was found for the Eating Assessment Tool or Postoperative Oral Dysfunction scale. Patients with OSCC may have decreased oral function because of the tumor at the time of diagnosis, which causes a decline in nutritional status. Preoperative interventions are necessary to improve nutrition based on the state of oral function.

Development of a Subjective Symptom Rating Scale for Postoperative Oral Dysfunction in Patients with Oral Cancer: Reliability and Validity of the Postoperative Oral Dysfunction Scale-10.

Currently, there is no scale to subjectively assess postoperative oral dysfunction in patients with oral cancer. The purpose of this study was to evaluate the reliability and validity of the Postoperative Oral Dysfunction Scale (POD-10) that we developed. Between September 2019 and August 2021, 62 eligible oral cancer patients (median age, 72 years; 42 men and 20 women) were enrolled in the study. The Cronbach's alpha coefficient, which indicates the internal consistency of the scale, was 0.94, and the intraclass correlation coefficient, which indicates reproducibility, was 0.85 (95% confidential interval: 0.40-0.96, p < 0.05). Concurrent validity testing showed a statistically significant correlation between POD-10 and Eating Assessment Tool (EAT-10) (r = 0.89, p < 0.05). To test discriminant validity, statistically significant differences were found between early-stage cancer (stage I and II) and advanced-stage cancer (stage III and IV) (p < 0.05). Twenty-four points were calculated as the cutoff value for POD-10 using receiver operating characteristic analysis to calculate the cutoff value. The POD-10 was shown to be a clinically reliable and valid scale that can be used to subjectively assess postoperative oral dysfunction in patients with oral cancer and is expected to be used as a simple diagnostic tool.

Proposal of Dental Hygiene Diagnosis for Cancer Patients Based on Dental Hygiene Process of Care in Acute Care Hospitals: A Narrative Review.

A narrative review was conducted to propose dental hygiene diagnoses for cancer patients based on dental hygiene process of care in acute care hospitals. Six researchers, including three dental hygienists, all with expertise in oral healthcare for patients with cancer, decided the review outline. All researchers reviewed the literature and developed terminology for dental hygiene diagnoses. The team then modified the terminology and discussed its clarity and acceptability to develop an initial list of dental hygiene diagnosis names according to the dental hygiene human needs conceptual model subscales. In wholesome facial image, one new diagnosis was developed. In protection from health risks, 15 new diagnoses were developed. In biologically sound and functional dentition, 10 new diagnoses were developed. In skin and mucous membrane integrity of the head and neck, 10 new diagnoses were developed. In freedom from head and neck pain, two new diagnoses were developed. In freedom from anxiety and stress, eight new diagnoses were developed. In responsibility for oral health, five new diagnoses were developed. In conceptualization and understanding, three new diagnoses were developed. Based on this study, it is necessary for the academic community to develop a better taxonomy of dental hygiene diagnoses pertaining to dental hygienist clinical practice.

Carbonyl Stress and Microinflammation-Related Molecules as Potential Biomarkers in Schizophrenia.

This literature review primarily aims to summarize our research, comprising both cross-sectional and longitudinal studies, and discuss the possibility of using microinflammation-related biomarkers as peripheral biomarkers in the diagnosis and monitoring of patients with schizophrenia. To date, several studies have been conducted on peripheral biomarkers to recognize the potential markers for the diagnosis of schizophrenia and to determine the state and effects of therapy in patients with schizophrenia. Research has established a correlation between carbonyl stress, an environmental factor, and the pathophysiology of neuropsychiatric diseases, including schizophrenia. In addition, studies on biomarkers related to these stresses have achieved results that are either replicable or exhibit consistent increases or decreases in patients with schizophrenia. For instance, pentosidine, an advanced glycation end product (AGE), is considerably elevated in patients with schizophrenia; however, low levels of vitamin B6 [a detoxifier of reactive carbonyl compounds (RCOs)] have also been reported in some patients with schizophrenia. Another study on peripheral markers of carbonyl stress in patients with schizophrenia revealed a correlation of higher levels of glyceraldehyde-derived AGEs with higher neurotoxicity and lower levels of soluble receptors capable of diminishing the effects of AGEs. Furthermore, studies on evoked microinflammation-related biomarkers (e.g., soluble tumor necrosis factor receptor 1) have reported relatively consistent results, suggesting the involvement of microinflammation in the pathophysiology of schizophrenia. We believe that our cross-sectional and longitudinal studies as well as various previous inflammation marker studies that could be interpreted from several perspectives, such as mild localized encephalitis and microvascular disturbance, highlighted the importance of early intervention as prevention and distinguished the possible exclusion of inflammations in schizophrenia.

High serum soluble tumor necrosis factor receptor 1 predicts poor treatment response in acute-stage schizophrenia.

Inflammation may be involved in the pathophysiology of schizophrenia. However, few cross-sectional or longitudinal studies have examined changes in biomarker expression to evaluate diagnostic and prognostic efficacy in acute-stage schizophrenia. We compared serum inflammatory biomarker concentrations in 87 patients with acute-stage schizophrenia on admission to 105 age-, sex-, and body mass index (BMI)-matched healthy controls. The measured biomarkers were soluble tumor necrosis factor receptor 1 (sTNFR1) and adiponectin, which are associated with inflammatory responses, and pigment epithelium-derived factor (PEDF), which has anti-inflammatory properties. We then investigated biomarker concentrations and associations with clinical factors in 213 patients (including 42 medication-free patients) and 110 unmatched healthy controls to model conditions typical of clinical practice. Clinical symptoms were assessed using the Brief Psychiatric Rating Scale and Global Assessment of Function. In 121 patients, biomarker levels and clinical status were evaluated at both admission and discharge. Serum sTNFR1 was significantly higher in patients with acute-stage schizophrenia compared to matched controls while no significant group differences were observed for the other markers. Serum sTNFR1 was also significantly higher in the 213 patients compared to unmatched controls. The 42 unmedicated patients had significantly lower PEDF levels compared to controls. Between admission and discharge, sTNFR1 levels decreased significantly; however, biomarker changes did not correlate with clinical symptoms. The discriminant accuracy of sTNFR1 was 93.2% between controls and patients, showing no symptom improvement during care. Inflammation and a low-level anti-inflammatory state may be involved in both schizophrenia pathogenesis and acute-stage onset. High serum sTNFR1 in the acute stage could be a useful prognostic biomarker for treatment response in clinical practice.

High doses of antipsychotic polypharmacy are related to an increase in serum levels of pentosidine in patients with schizophrenia.

BACKGROUND: Carbonyl stress in patients with schizophrenia has been reported to be reflected by an increase in peripheral pentosidine levels. This cohort study tested whether the accumulation of pentosidine was related to the disease severity or the treatment (routine administration of high antipsychotic doses). METHODS: We followed up our original investigation using a new group of 137 patients with acute schizophrenia and 45 healthy subjects, and then pooled the two cohorts to conduct the following analysis on a total of 274 patients. The associations of serum pentosidine and pyridoxal levels with duration of education, estimated duration of medication, the severity of symptoms, and daily doses of antipsychotics, antiparkinsonian drugs, and anxiolytics were evaluated by multiple linear regression analysis. RESULTS: The combined cohort of 274 patients exhibited abnormally high serum levels of pentosidine, were associated with a higher daily dose of antipsychotic drugs and a longer estimated duration of medication without statistical significance of diagnosis. This was also observed in the patients treated with antipsychotic polypharmacy, but the serum pentosidine levels of patients treated with first- or second-generation antipsychotic monotherapy showed no relationship with these two variables. CONCLUSION: High levels of serum pentosidine were associated with high daily doses of antipsychotic drugs and a longer estimated duration of medication in patients treated with antipsychotic polypharmacy.

Autocrine pathways involving S100A8 and/or S100A9 that are postulated to regulate the immunological functions of macrophages in rats.

The development of ulcerative colitis (UC) is closely associated with abnormally functioning macrophages. Rat S100A8 (r-S100A8) and r-S100A9 (S100 proteins) is abundantly expressed in immune cells of myeloid origin, macrophages; however, it remains unclear why r-S100A9 is dominantly expressed in the macrophages of UC rats (UCR). The purpose of this study was to verify the immunological roles of S100 proteins in UCR. We observed the distribution of S100 protein-positive macrophages in the large colons of UCR using a fluorescent immunological staining method, so that S100 protein-positive macrophages were restricted to the rectal tissues of the UCR, and that the mRNA levels of r-S100A8 and r-S100A9 were up-regulated by stimulation with recombinant rat S100A8 (rr-S100A8) alone and rr-S100A9 alone, respectively. When the changes in the mRNA levels of r-S100A8 and r-S100A9 in macrophages were examined in in vitro study by PCR and real-time PCR, the mRNA levels of anti-inflammatory and inflammatory cytokines increased selectively after stimulation with rr-S100A8 alone and rr-S100A9 alone, respectively. These results suggest that autocrine signal transduction pathways involving S100 proteins regulate the immunological functions of macrophages to maintain homeostasis in the gastrointestinal tract. This may be depended on expression balance of S100 proteins in macrophages. It is strongly suggested that in UCR the immune functions of macrophages are regulated in a complex manner by r-S100A8 and/or r-S100A9 through undefined autocrine pathways on the cells.

Clinical usefulness of the PAXgene™ bone marrow RNA system for stabilizing total RNA.

The collection of clinical samples, such as bone marrow (BM) and peripheral blood, is an important procedure for the extraction of the cellular RNA. It is essential to preserve the extracted RNA during and after the collection of clinical samples to ensure the accurate analysis of gene expression. To date, the PAXgene™ Blood RNA System has been proven useful for stabilizing RNA extracted from peripheral blood; however, a problem concerning the stability of the total RNA stored using the system has been identified. The PAXgene™ Bone Marrow RNA System (BM system) is a newly developed system, and its clinical usefulness as a stabilizer for the cellular RNA in BM and peripheral blood was investigated with respect to the quality of RNA extracted using this system. A quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was carried out using total RNA extracted with the BM system, which showed that total RNA was more stable in the BM system than in the conventional system, indicating that the BM system can be applied to RT-PCR. The BM system enabled us to detect Wilms' tumor suppressor gene (WT1) more effectively than the conventional system. In conclusion, the BM system is clinically valuable for extracting and stabilizing total RNA of high quality.

Acquired resistance of leukemic cells to AraC is associated with the upregulation of aldehyde dehydrogenase 1 family member A2.

The elucidation of drug resistance mechanisms is important in the development of clinical therapies for the treatment of leukemia. To study the drug resistance mechanisms, protein expression profiles of 1-ß-D-arabinofuranosylcytosine (AraC)-sensitive K562 (K562S) cells and AraC-resistant K562 (K562AC) cells were compared using two-dimensional fluorescence difference gel electrophoresis. In a comparison of protein expression profiles, 2073 protein spots were found to be altered, and 15 proteins of them were remarkably altered. These proteins were identified by mass spectrometry. The most differently expressed proteins were aldehyde dehydrogenase 1 family member A2 (ALDH1A2) and vimentin. Both proteins were verified using reverse transcriptase polymerase chain reaction and Western blot analysis. ALDH1A2 protein was found to be effective in AraC resistance. ALDH1A2 knock-down induced sensitivity to AraC treatment in K562AC cells, and ALDH1A2 overexpressed K562S cells acquired the AraC resistance. Furthermore, the findings also suggest that ALDH1A2 expression is increased after the appearance of AraC resistance in clinical cases. These results will be helpful in understanding the mechanism of AraC resistance.

[Current update and testing procedures for genetic diagnosis in malignant neoplasm: additional information on pathological tests].

Targeted therapy refers to anticancer treatment which specifically targets key molecules of cancer cells. The higher levels of expression of the epidermal growth factor receptor (EGFR) have also been shown to be correlated with non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). Potential biomarkers should be investigated for the selection of patients with NSCLC most likely to benefit from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib. Cetuximab is a monoclonal antibody that binds with high affinity to the EGFR, which is a prime target for new anticancer therapy. However, the predictive value of EGFR expression and mutation of the K-ras gene has been assessed in response to cetuximab. Many molecular techniques are available to assay for these biomarkers. In this review, we present the current assessments of evidence for using these methods as biomarkers for molecular target-based therapy.