Six-Gene Signature for Differential Diagnosis and Therapeutic Decisions in Non-Small-Cell Lung Cancer-A Validation Study.

Non-small-cell lung cancer (NSCLC) poses a challenge due to its heterogeneity, necessitating precise histopathological subtyping and prognostication for optimal treatment decision-making. Molecular markers emerge as a potential solution, overcoming the limitations of conventional methods and supporting the diagnostic-therapeutic interventions. In this study, we validated the expression of six genes (MIR205HG, KRT5, KRT6A, KRT6C, SERPINB5, and DSG3), previously identified within a 53-gene signature developed by our team, utilizing gene expression microarray technology. Real-time PCR on 140 thoroughly characterized early-stage NSCLC samples revealed substantial upregulation of all six genes in squamous cell carcinoma (SCC) compared to adenocarcinoma (ADC), regardless of clinical factors. The decision boundaries of the logistic regression model demonstrated effective separation of the relative expression levels between SCC and ADC for most genes, excluding KRT6C. Logistic regression and gradient boosting decision tree classifiers, incorporating all six validated genes, exhibited notable performance (AUC: 0.8930 and 0.8909, respectively) in distinguishing NSCLC subtypes. Nevertheless, our investigation revealed that the gene expression profiles failed to yield predictive value regarding the progression of early-stage NSCLC. Our molecular diagnostic models manifest the potential for an exhaustive molecular characterization of NSCLC, subsequently informing personalized treatment decisions and elevating the standards of clinical management and prognosis for patients.

Evaluation of the functioning of long-term at-home nursing care in Poland from the perspective of care providers: Mixed methods study.

AIMS AND OBJECTIVES: This study aimed to analyse and evaluate the functioning of long-term at-home nursing care (LTHNC) based on the opinions of its service providers. BACKGROUND: Long-term at-home nursing care is a form of care for patients who do not need hospital treatment but need systematic nursing care because of their health problems. LTHNC in Poland involves guaranteed care services financed from universal health insurance contributions pursuant to contracts with the National Health Fund (NHF); the program has existed since 2004. DESIGN: A sequential-explanatory mixed-method design was used. The study was carried out using both quantitative and qualitative research methods. METHODS: A questionnaire was distributed amongst 1119 care providers (the response rate was 38.2%). The qualitative research comprised semi-structured interviews with ten care providers, namely three nurses managing LTHNC facilities and seven nurses directly providing services as part of LTHNC. The STROBE checklist was used in reporting this study. RESULTS: We found that the main reasons for contracting LTHNC services were the increasing demand for this form of care, financial motives and an opportunity to introduce new organisational solutions. Our study shows that LTHNC is beneficial not only for the patients, but also for the nurses who provide the care. On the one hand, LTHNC provides positive results for patients and their caregivers (family members), and on the other hand, it affords a sense of satisfaction to the nurses and contributes to the development of their professional independence. CONCLUSIONS: According to care providers, improving accessibility through increasing the number of contracted services as well as raising the pay for 1 day of care per patient may improve the functioning of LTHNC. RELEVANCE TO CLINICAL PRACTICE: The results of our study are a source of information for those who organise health care and administer resources on how to improve the functioning of LTHNC.

Assessment of Ceragenins in Prevention of Damage to Voice Prostheses Caused by Candida Biofilm Formation.

This study aimed to investigate the potential application of ceragenins (CSAs) as new candidacidal agents to prevent biofilm formation on voice prostheses (VPs). The deterioration of the silicone material of VPs is caused by biofilm growth on the device which leads to frequent replacement procedures and sometimes serious complications. A significant proportion of these failures is caused by Candida species. We found that CSAs have significant candidacidal activities in vitro (MIC; MFC; MBIC), and they effectively eradicate species of yeast responsible for VP failure. Additionally, in our in vitro experimental setting, when different Candida species were subjected to CSA-13 and CSA-131 during 25 passages, no tested Candida strain showed the significant development of resistance. Using liquid chromatography-mass spectrometry (LC-MS), we found that VP immersion in an ethanol solution containing CSA-131 results in silicon impregnation with CSA-131 molecules, and in vitro testing revealed that fungal biofilm formation on such VP surfaces was inhibited by embedded ceragenins. Future in vivo studies will validate the use of ceragenin-coated VP for improvement in the life quality and safety of patients after a total laryngectomy.

Impact of Acute Pancreatic Injury on Sphingolipid Metabolism in the Salivary Glands.

Acute pancreatic injury can be related to both parenchymal (responsible for exocrine functions) and islet (mainly ß-cells, responsible for endocrine functions) damage. During embryonic development, both the salivary glands and the pancreas originate from the foregut, which explains many of the observed histological and functional similarities between these two organs. The relationship between several diseases of the pancreas and salivary glands, resulting from morphological and functional similarities, is well established. Sphingolipids constitute a class of biologically active molecules involved in numerous physiological and pathological processes, including acute pancreatitis (AP) and diabetes mellitus. However, the effect of AP on sphingolipid metabolism in the salivary glands remains uncertain. In the presented study, we examined the effect of AP and type 1 diabetes mellitus on sphingolipid metabolism in the salivary glands of rats. We demonstrated that acute pancreatic injury, related to both exocrine and endocrine functions, affects the metabolism of sphingolipids in the parotid, but not submandibular, salivary glands.

The Impact of High-Fat Diet on Mitochondrial Function, Free Radical Production, and Nitrosative Stress in the Salivary Glands of Wistar Rats.

Oxidative stress plays a crucial role in the salivary gland dysfunction in insulin resistance; however, the cause of increased free radical formation in these conditions is still unknown. Therefore, the aim of the study was to investigate the effect of high-fat diet (HFD) on the mitochondrial respiratory system, prooxidant enzymes, ROS production, and nitrosative/oxidative stress in the submandibular and parotid glands of rats. The experiment was performed on male Wistar rats divided into two groups (n = 10): control and HFD. The 8-week feeding of HFD affects glucose metabolism observed as significant increase in plasma glucose and insulin as well as HOMA-IR as compared to the control rats. The activity of mitochondrial Complex I and Complex II+III was significantly decreased in the parotid and submandibular glands of HFD rats. Mitochondrial cytochrome c oxidase (COX) activity and the hydrogen peroxide level were significantly increased in the parotid and submandibular glands of the HFD group as compared to those of the controls. HFD rats also showed significantly lower reduced glutathione (GSH) and reduced : oxidized glutathione (GSH : GSSG) ratio, as well as a higher GSSG level in the parotid glands of HFD rats. The activity of NADPH oxidase, xanthine oxidase, and levels of oxidative/nitrosative stress (malonaldehyde, nitric oxide, nitrotyrosine, and peroxynitrite) and inflammation/apoptosis (interleukin-1ß and caspase-3) biomarkers were statistically elevated in the HFD group in comparison to the controls. HFD impairs mitochondrial function in both types of salivary glands by enhancing ROS production, as well as stimulating inflammation and apoptosis. However, free radical production, protein nitration, and lipid peroxidation were more pronounced in the parotid glands of HFD rats.

Inequalities in breast cancer incidence and stage distribution between urban and rural female population in Swietokrzyskie Province, Poland.

INTRODUCTION AND OBJECTIVE: One of the main factors determining the burden of breast cancer is the effectiveness of measures taken to combat this cancer including urban-rural differences. The aim of the study was to analyse the differences in breast cancer incidence and disease stage distribution among urban and rural women in the Swietokrzyskie Province as a part of a strategy for breast cancer control. MATERIAL AND METHODS: The study of disease stage distribution included 483 female residents of Swietokrzyskie Province who were diagnosed in 2013 with invasive breast cancer, and reported to Swietokrzyskie Office for Cancer Registration. Urban-rural differences in breast cancer incidence in 2002-2013 were presented using Range Ratio (RR). Changes in incidence trends in urban and rural areas were analysed using joinpoint models. Annual Percentage Change (APC) of the rates was calculated for each time trend. RESULTS: Breast cancer incidence rate in the urban female population was higher than in rural women with RR, amounting to 1.43. However, the analysis of trends showed that the pace and direction of change were developing negatively among inhabitants of rural areas. In 2002-2013, in rural women, the age-standardized rate (ASR) values increased by 2.8% per year (p<0.05). The course of ASR trends showed statistically significant urban-rural differences (p=0.004). Analysis of urban-rural differences in disease stage distribution revealed a non-significantly higher proportion of cases with localised stage in urban than in rural areas, amounting to 51.0% and 43.9%, respectively. CONCLUSIONS: Existing health inequalities indicate the need to intensify activities in rural areas and should be the starting point for making key decisions in combating breast cancer.

Myriocin treatment affects lipid metabolism in skeletal muscles of rats with streptozotocin-induced type 1 diabetes.

PURPOSE: The aim of this work was to assess the effect(s) of de novo ceramide synthesis inhibition on lipid metabolism in skeletal muscle tissue of type 1 diabetic rats. The latter seems to be of vital importance, since previous works have shown its positive influence on lipid metabolism and glucose homeostasis in the case of its counterpart - type 2 diabetes. MATERIALS/METHODS: The animals were randomly assigned to one of the following groups: C - control, M - myriocin (ceramide de novo synthesis inhibitor), D - diabetes (induced by streptozotocin injections); D+M - diabetes+myriocin. We have evaluated intracellular concentration of key sphingolipid species, via chromatography (GC and HPLC), and the activity of their most important enzymes, using radiometric approach. The aforementioned assessments were evaluated in respect to the three different types of muscle tissue representing different spectra of muscle metabolism (soleus - oxidative, red gastrocnemious - oxidative-glycolytic, white gastrocnemious - glycolytic). RESULTS: Interestingly, our therapeutic intervention not only lowered the level of ceramide, its precursors (sphinganine) and derivatives (sphingosine and sphingosine-1-phosphate), but also reduced other lipid species (triacylglycerols, diacylglycerols and free fatty acids) content, thus improving glucose homeostasis in type 1 diabetic animals. CONCLUSIONS: In the light of the results ensuing from this study, it seems conceivable that the reduction of intramuscular ceramide production and accumulation could bestow an insulin-sensitizing effect. If so, then SPT inhibition could find potential future applications as a therapeutic intervention aimed to mitigate the effects of insulin resistance.

Insulin Resistance and Obesity Affect Lipid Profile in the Salivary Glands.

In today's world wrong nutritional habits together with a low level of physical activity have given rise to the development of obesity and its comorbidity, insulin resistance. More specifically, many researches indicate that lipids are vitally involved in the onset of a peripheral tissue (e.g., skeletal muscle, heart, and liver) insulin resistance. Moreover, it seems that diabetes can also induce changes in respect of lipid composition of both the salivary glands and saliva. However, judging by the number of research articles, the salivary glands lipid profile still has not been sufficiently explored. In the current study we aim to assess the changes in the main lipid fractions, namely, triacylglycerols, phospholipids, free fatty acids, and diacylglycerols, in the parotid and the submandibular salivary glands of rats exposed to a 5-week high fat diet regimen. We observed that the high caloric fat diet caused a significant change in the salivary glands lipid composition, especially with respect to PH and TG, but not DAG or FFAs, classes. The observed reduction in PH concentration is an interesting phenomenon frequently signifying the atrophy and malfunctions in the saliva secreting organs. On the other hand, the increased accumulation of TG in the glands may be an important clinical manifestation of metabolic syndrome and type 2 diabetes mellitus.