The Effect of Loneliness on Death Anxiety in the Elderly During the COVID-19 Pandemic.

The aim of the study is to determine the effect on death anxiety of loneliness in the elderly during the COVID-19 pandemic. The population of this study that is descriptive and cross-sectional type consist of 354 elderly who meet the inclusion criteria from three different associations operating for charitable purposes in a city center located in north-west Turkey. The average score of Loneliness Scale of Elderly (LSE) of the elderly was determined as 11.39 ± 5.31, and the average score of Death Anxiety Scale (DAS) of the elderly was determined as 8.54 ± 4.82. According to these results, it was found that the elderly experienced acceptable levels of loneliness and moderate death anxiety. A statistically significant difference was found in the LSE and DAS scores of the elderly according to their age, marital status, education status, chronic illness status and living at home with relatives. In addition, during the COVID-19 epidemic, the scale scores of the elderly who have increased worries, who have a hobby at home, and who communicate with their relatives via social media/mobile phones were found to be statistically significant (p < 0.05).

Sex Differences Across the Life Course: A Focus On Unique Nutritional and Health Considerations among Women.

In the United States, women, while having a longer life expectancy than men, experience a differential risk for chronic diseases and have unique nutritional needs based on physiological and hormonal changes across the life span. However, much of what is known about health is based on research conducted in men. Additional complexity in assessing nutritional needs within gender include the variations in genetics, body compositions, hormonal milieus, underlying chronic diseases, and medication usage, with this list expanding as we consider these variables across the life course. It is clear women experience nutrient shortfalls during key periods of their lives, which may differentially impact their health. Consequently, as we move into the era of precision nutrition, understanding these sex- and gender-based differences may help optimize recommendations and interventions chosen to support health and weight management. Recently, a scientific conference was convened with content experts to explore these topics from a life-course perspective at biological, physiological, and behavioral levels. This publication summarizes the presentations and discussions from the workshop and provides an overview of important nutrition and related lifestyle considerations across the life course. The landscape of addressing female-specific nutritional needs continues to grow; now more than ever, it is essential to increase our understanding of the physiological differences between men and women, and determine how these physiological considerations may aid in optimizing nutritional strategies to support certain personal goals related to health, quality of life, sleep, and exercise performance among women.

The effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes in patients with breast cancer.

Aim: This study investigated the effect of neoadjuvant chemotherapy (NAC) on stromal tumor-infiltrating lymphocytes (sTILs) and their treatment response. Materials & methods: 115 patients with pre-NAC core biopsies and post-NAC surgical resection specimens were reviewed. Results: There was no significant change between pre- and post-treatment sTILs. Both pre- and post-NAC sTILs were significantly lower in patients with luminal A subtype. An increase in sTILs was observed in 21 (25.9%) patients after NAC, a decrease in 29 (35.8%) and no change in 31 (38.3%; p = 0.07). Pretreatment sTIL density was independent predictor of pathological complete response in multivariate analyses (odds ratio: 1.025, 95% CI: 1.003-1.047; p = 0.023). Conclusion: High sTIL density in core biopsies was independently related to pathological complete response. In addition, ER appears to be the most crucial factor determining the rate of sTIL.

New studies have shown that the tumor microenvironment is critical in tumor behavior. Immune cells surrounding tumor cells are the main components of the tumor microenvironment. Our study aimed to investigate the change in immune cells before and after chemotherapy in breast cancer patients. Our study included 115 patients. All patients underwent chemotherapy before surgery to shrink the tumor. Tru-cut biopsy pieces and the breast tissue obtained after surgery were examined. The presence of estrogen or progesterone receptors on tumor cells decreased the number of immune cells surrounding the tumor cells. The number of immune cells did not decrease after chemotherapy. Another finding was that the greater the number of immune cells around the tumor, the more likely that the tumor would disappear after chemotherapy.

"Sleep Quality and Depression Level in Nurses in COVID-19 Pandemic".

The COVID-19 spread rapidly all over the world and pandemic process has negatively affected nurses. Sleep disorders and depression are among these negative effects. Managers' awareness of problems experienced by nurses and taking precautions will increase employee and patient satisfaction and provide quality patient care. The study was conducted in descriptive, cross-sectional and correlational design to explain nurses' sleep quality and depression levels and relationship between them during the COVID-19 pandemic with 142 nurses who completed Personel Information Form, Pittsburgh Sleep Quality Index (PSQI) and Beck Depression Index (BDI). Sleep quality of nurses (64.8%) was poor, 33.1% had depression, and high school education, having a chronic illness and PSQI score increased the risk of depression level of nurses. Results highlight COVID-19 pandemic affected nurses' sleep quality and depression levels. All managers should be pioneers in providing psychological support to nurses and preparing and implementing a program for prevention of insomnia and depression.

LONG-TERM SURVIVAL EFFECTS OF PREOPERATIVE BREAST MRI IN PATIENTS WITH BREAST-CONSERVING SURGERY.

The benefit of breast magnetic resonance imaging (MRI) in breast-conserving surgery (BCS) is unclear. Our study compared breast cancer patients with and without preoperative breast MRI and their long-term oncologic outcomes are reported. A total of 1378 BCS cases with early breast cancer between 1996 and 2017 were reviewed. Patients with carcinoma in situ or neoadjuvant treatment or having breast MRI after tumor excision were excluded. Of 1378 patients, 270 (19.5%) had preoperative MRI. There were no significant differences regarding T and N stage and molecular subtypes between the groups. Surgical margins were significantly wider in the breast MRI group. Five-year overall survival (OS) was 96.9% in the MRI group and 94.3% in the control group, and this difference was not significant (p=0.11). Five-year local-regional recurrence-free survival (LRFS) was not significantly different either (98.8% and 96.5%, respectively, p=0.41). When analyses were repeated only for patients with hormone receptor-negative or triple-negative breast cancer, there was still no significant difference in OS, LRFS, or disease-free survival. In conclusion, MRI does not seem necessary in all patients undergoing BCS. New prospective randomized controlled trials are needed to determine appropriate use of preoperative MRI and its effects on oncologic outcomes in early breast cancer patients.

Dietary Supplement Use in Gastrointestinal Symptom Management and Effect on Hopelessness Levels in Patients With Irritable Bowel Syndrome.

This study was conducted to determine the dietary supplement (DS) use in gastrointestinal symptom management, and its effect on hopelessness levels in patients with irritable bowel syndrome (IBS). The universe of this cross-sectional study consisted of 132 patients presenting at the polyclinic, while the sample consisted of 127 patients who meet the inclusion criteria to study. Data were collected using a patient identification form including sociodemographic characteristics and DS use, the Gastrointestinal Symptom Rating Scale, and the Beck Hopelessness Scale. The frequency of DS use in the last year among patients with IBS was 73.2%. Younger, women, those with graduate education, and those with better economic status were found to prefer more DS (P < .0001). Nausea and decreased passage of stools were predictors of DS use with a rate of 40.9% (R = 0.409, P < .0001). The patients were found to use mint oil (35.6%), mint juice (24.6%), lemon (20.5%) for nausea, and apricots (48.2%) and dietary fibers (16.9%) for decreased passage of stools. Patients who did not use DSs were found to be more hopeless (P < .03). It was found that 73.2% of patients with IBS used DSs. Patients who did not use DSs were found to be more hopeless. DSs with proven effectiveness can be integrated into medical treatments.

Validity and reliability of the Turkish version of the weight Self-stigma questionnaire.

OBJECTIVE: To test the validity and reliability of the Turkish version of the Weight Self-Stigma Questionnaire. METHODS: The methodological, descriptive study was conducted at the Bulent Ecevit University, Zonguldak, Turkey, from January to June, 2016, and comprised obese patients presenting at the Endocrinology and Diabetes polyclinic tied to the university. Data was collected using patient identification form and Weight Self-Stigma Questionnaire. SPSS 18 was used for statistical analysis. RESULTS: Of the 151 subjects, 97(64.2%) were female and 54(35.8%) were male. Two-factor structure explained 58% of the total variance in the Weight Self-Stigma Questionnaire. The Cronbach alpha internal consistency coefficient of the Turkish version was 0.876, indicating high internal consistency. The two factors found in the confirmatory factor analysis had Cronbach alpha values of 0.820 and 0.830. CONCLUSIONS: The validity and reliability of Weight Self-Stigma Questionnaire was found to be high in Turkey.

Synchronous and metachronous bilateral breast cancer: A long-term experience.

PURPOSE: The objective of this study was to assess the demographic, pathologic and survival characteristics of patients who were diagnosed as having bilateral breast cancer. METHODS: A review was conducted of the records pertaining to patients who presented to our clinic and were diagnosed as having breast cancer. Any second cancer diagnosed within 12 months of initial diagnosis was defined as synchronous bilateral breast cancer. Assessment included treatments administered to the patients and survival rates, as well as their demographic, reproductive and pathologic features. RESULTS: The total number of patients who were diagnosed as having bilateral breast cancer in the context of the present study was 99. Among the patients with synchronous breast cancer, the median age at the time of initial diagnosis was found as 57 years. The median age of the discovery of first tumor among the patients with metachronous tumor was 52 years and the median age of second tumor detection was 59 years. Family history in metachronous tumor was significantly greater (p=0.041). The median time of metachronous cancer incidence was 96 months. The length of disease-free period among the patients with synchronous tumor was 126.3 months, whereas it was 243.7 months in those with metachronous tumor (p=0.041). CONCLUSION: The incidence rate of synchronous breast tumors has been rising thanks to growing awareness and the leading-edge imaging methods. The fact that the second tumor developed after more than 5 years among the patients with metachronous cancer gave rise to the increased rate of survival.

Complementary Health Approaches Used in the Intensive Care Unit.

Intensive care units are care centers where, in order to provide the maximum benefit to individuals whose life is in danger, many lifesaving technological tools and devices are present, and morbidity and mortality rates are high. In the intensive care unit, when classic treatments fail or become unbearable because of side effects, complementary methods have been suggested to be the best alternative. Complementary health approaches are methods that are used both for the continuation and the improvement of the well-being of an individual and as additions to medical treatments that are based on a holistic approach. These applications are especially helpful in the treatment of the stresses, anxieties, and other symptoms of unstable patients in the intensive care unit who do not tolerate traditional treatment methods well, increasing their psychological and physiological well-being, helping them sleep and rest. In intensive care patients, in order to decrease the incidence of postoperative atrial fibrillation, antiemetic and medicine needs, mechanical ventilation duration, and the intensity of the disease as well as to cope with symptoms such as pain, anxiety, physiological parameters, dyspnea, and sleep problems, body-mind interventions such as massage, reflexology, acupressure, aromatherapy, music therapy, energy therapies (healing touch, therapeutic touch, the Yakson method), and prayer are used as complementary health approaches.

The Effect of Music Therapy on Anxiety and Various Physical Findings in Patients With COPD in a Pulmonology Service.

This interventional study was carried out to determine the effect of music therapy on anxiety and the various physical findings in patients with chronic obstructive pulmonary disease in the pulmonary diseases service. Ninety-six patients (28 females, 68 males) of 114 adult patients who were hospitalized between November 10, 2013, and March 10, 2014, were included in the study. Ninety-six patients were separated in 3 groups. The data for the study were collected from a questionnaire form of sociodemographic and clinical characteristics, a patient follow-up form, and the Beck Anxiety Scale. SPPS 11.5 was used for data analysis. The Kolmogorov-Smirnov Test was used to determine whether the data showed normal distribution. The nonparametric Kruskal-Wallis Test was used to determine the differences between mean anxiety scores on day 0, day 5, and day 15, and the differences in physiological findings on day 0, day 5, and day 15. There was a significant decrease in anxiety level average on day 5 (P ≤ .0001) and day 15 (P ≤ .0001) of the study in both the Western classical music and Turkish classical music groups compared with control group. There was also a significant decrease in systolic blood pressure and diastolic blood pressure averages in both music groups compared with control group (P ≤ .005). There was no significant difference in heart rates and respiration rate average between the Western classical music and Turkish classical music groups compared with the control group (P > .05).

Receptor discordance rate and its effects on survival in primary and recurrent breast cancer patients.

PURPOSE: The receptor status of breast cancer plays a critical role in clinical practice. During the metastatic process, a change in the biological characteristics of the tumor can be seen. This study aimed to investigate the hormone receptor and HER2 status changes between primary and recurrent breast cancers and their effect on survival. METHODS: Eighty-six breast cancer patients with biopsy- proven local recurrences or distant metastases during the follow-up period were included in the study. Patients with metastatic disease at the time of first diagnosis or with history of previous neoadjuvant chemotherapy were excluded. RESULTS: Forty-three of the 86 patients (50%) had changes in at least one of the estrogen receptor (ER), progesterone receptor (PR), or HER2. ER, PR and HER2 discordance rates were 12.7, 38.3, and 15.1%, respectively, and PR discordance was significantly higher (p=0.000). Among all molecular subtypes, the triple negative breast cancer (TNBC) subtype showed the least change. When the effect of chemotherapy on receptor change was analyzed, PR discordance was significantly higher in the group who received chemotherapy (p=0.029). Analysis of the hormonotherapy effects on receptor discordance revealed results similar to those of chemotherapy. Only the PR discordance was significantly greater in the group that received hormonotherapy (p=0.000). None of the three receptor discordances or loss of any receptor were related to survival. Primary tumor TNBC subtype and disease-free-interval (DFI) shorter than 5 years were found as independent prognostic factors that negatively affected overall survival (OS). CONCLUSION: This study showed that during recurrent disease there was 50% discordance in the expression of ER, PR, and HER2. The receptor showing the greatest discordance and influence from the systemic treatment was PR. A significant relationship between receptor discordance and survival could not be demonstrated in our study.

Ligand Accessibility and Bioactivity of a Hormone-Dendrimer Conjugate Depend on pH and pH History.

Estrogen conjugates with a polyamidoamine (PAMAM) dendrimer have shown remarkably selective regulation of the nongenomic actions of estrogens in target cells. In response to pH changes, however, these estrogen-dendrimer conjugates (EDCs) display a major morphological transition that alters the accessibility of the estrogen ligands that compromises the bioactivity of the EDC. A sharp break in dynamic behavior near pH 7 occurs for three different ligands on the surface of a PAMAM-G6 dendrimer: a fluorophore (tetramethylrhodamine [TMR]) and two estrogens (17α-ethynylestradiol and diphenolic acid). Collisional quenching and time-resolved fluorescence anisotropy experiments with TMR-PAMAM revealed high ligand shielding above pH 7 and low shielding below pH 7. Furthermore, when the pH was cycled from 8.5 (conditions of ligand-PAMAM conjugation) to 4.5 (e.g., endosome/lysosome) and through 6.5 (e.g., hypoxic environment) back to pH 8.5, the 17α-ethynylestradiol- and diphenolic acid-PAMAM conjugates experienced a dramatic, irreversible loss in cell stimulatory activity; dynamic NMR studies indicated that the hormonal ligands had become occluded within the more hydrophobic core of the PAMAM dendrimer. Thus, the active state of these estrogen-dendrimer conjugates appears to be metastable. This pH-dependent irreversible masking of activity is of considerable relevance to the design of drug conjugates with amine-bearing PAMAM dendrimers.

The forkhead transcription factor FOXM1 promotes endocrine resistance and invasiveness in estrogen receptor-positive breast cancer by expansion of stem-like cancer cells.

INTRODUCTION: The forkhead transcription factor FOXM1 coordinates expression of cell cycle-related genes and plays a pivotal role in tumorigenesis and cancer progression. We previously showed that FOXM1 acts downstream of 14-3-3ζ signaling, the elevation of which correlates with a more aggressive tumor phenotype. However, the role that FOXM1 might play in engendering resistance to endocrine treatments in estrogen receptor-positive (ER+) patients when tumor FOXM1 is high has not been clearly defined yet. METHODS: We analyzed FOXM1 protein expression by immunohistochemistry in 501 ER-positive breast cancers. We also mapped genome-wide FOXM1, extracellular signal-regulated kinase 2 and ERα binding events by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) in hormone-sensitive and resistant breast cancer cells after tamoxifen treatment. These binding profiles were integrated with gene expression data derived from cells before and after FOXM1 knockdown to highlight specific FOXM1 transcriptional networks. We also modulated the levels of FOXM1 and newly discovered FOXM1-regulated genes and examined their impact on the cancer stem-like cell population and on cell invasiveness and resistance to endocrine treatments. RESULTS: FOXM1 protein expression was high in 20% of the tumors, which correlated with significantly reduced survival in these patients (P = 0.003 by logrank Mantel-Cox test). ChIP-seq analyses revealed that FOXM1 binding sites were enriched at the transcription start site of genes involved in cell-cycle progression, maintenance of stem cell properties, and invasion and metastasis, all of which are associated with a poor prognosis in ERα-positive patients treated with tamoxifen. Integration of binding profiles with gene expression highlighted FOXM1 transcriptional networks controlling cell proliferation, stem cell properties, invasion and metastasis. Increased expression of FOXM1 was associated with an expansion of the cancer stem-like cell population and with increased cell invasiveness and resistance to endocrine treatments. Use of a selective FOXM1 inhibitor proved very effective in restoring endocrine therapy sensitivity and decreasing breast cancer aggressiveness. CONCLUSIONS: Collectively, our findings uncover novel roles for FOXM1 and FOXM1-regulated genes in promoting cancer stem-like cell properties and therapy resistance. They highlight the relevance of FOXM1 as a therapeutic target to be considered for reducing invasiveness and enhancing breast cancer response to endocrine treatments.

Integrative genomics of gene and metabolic regulation by estrogen receptors α and ß, and their coregulators.

The closely related transcription factors (TFs), estrogen receptors ERα and ERß, regulate divergent gene expression programs and proliferative outcomes in breast cancer. Utilizing breast cancer cells with ERα, ERß, or both receptors as a model system to define the basis for differing response specification by related TFs, we show that these TFs and their key coregulators, SRC3 and RIP140, generate overlapping as well as unique chromatin-binding and transcription-regulating modules. Cistrome and transcriptome analyses and the use of clustering algorithms delineated 11 clusters representing different chromatin-bound receptor and coregulator assemblies that could be functionally associated through enrichment analysis with distinct patterns of gene regulation and preferential coregulator usage, RIP140 with ERß and SRC3 with ERα. The receptors modified each other's transcriptional effect, and ERß countered the proliferative drive of ERα through several novel mechanisms associated with specific binding-site clusters. Our findings delineate distinct TF-coregulator assemblies that function as control nodes, specifying precise patterns of gene regulation, proliferation, and metabolism, as exemplified by two of the most important nuclear hormone receptors in human breast cancer.

Mechanisms enforcing the estrogen receptor ß selectivity of botanical estrogens.

Because little is known about the actions of botanical estrogens (BEs), widely consumed by menopausal women, we investigated the mechanistic and cellular activities of some major BEs. We examined the interactions of genistein, daidzein, equol, and liquiritigenin with estrogen receptors ERα and ERß, with key coregulators (SRC3 and RIP140) and chromatin binding sites, and the regulation of gene expression and proliferation in MCF-7 breast cancer cells containing ERα and/or ERß. Unlike the endogenous estrogen, estradiol (E2), BEs preferentially bind to ERß, but their ERß-potency selectivity in gene stimulation (340- to 830-fold vs. E2) is enhanced at several levels (coregulator recruitment, chromatin binding); nevertheless, at high (0.1 or 1 µM) concentrations, BEs also fully activate ERα. Because ERα drives breast cancer cell proliferation and ERß dampens this, the relative levels of these two ERs in target cells and the BE dose greatly affect gene expression and proliferative response and will be crucial determinants of the potential benefits vs. risks of BEs. Our findings reveal key and novel mechanistic differences in the estrogenic activities of BEs vs. E2, with BEs displaying patterns of activity distinctly different from those seen with E2 and provide valuable information to inform future studies.

Radionuclide imaging for breast cancer diagnosis and management: is technetium-99m tetrofosmin uptake related to the grade of malignancy?

There are different scoring systems available for determining the grade of breast cancer malignancy. Breast cancer tumors have been described for grades 1-3 using the modified Nottingham-Bloom-Richardson grading system. Determining the grade is very important for the clinicians to choose the best treatment options. Technetium-99m methoxy isobutyl isonitrile ((99m)Tc-MIBI) and pentavalent (99m)Tc-dimercaptosuccinic acid ((99m)Tc(V)-DMSA) scintigraphy have been used and are under evaluation for being prognostic factors for breast carcinoma. Radionuclide breast imaging not only visualizes the lesion site but also reflects specific biological and functional lesion features, including perfusion, proliferative potential, metabolic activity and receptor status.

Targeting NAD+ Metabolism: Preclinical Insights into Potential Cancer Therapy Strategies.

NAD+ is one of the most important metabolites for cellular activities, and its biosynthesis mainly occurs through the salvage pathway using the nicotinamide phosphoribosyl transferase (NAMPT) enzyme. The main nicotinamide adenine dinucleotide (NAD) consumers, poly-ADP-ribose-polymerases and sirtuins enzymes, are heavily involved in DNA repair and chromatin remodeling. Since cancer cells shift their energy production pathway, NAD levels are significantly affected. NAD's roles in cell survival led to the use of NAD depletion in cancer therapies. NAMPT inhibition (alone or in combination with other cancer therapies, including endocrine therapy and chemotherapy) results in decreased cell viability and tumor burden for many cancer types. Many NAMPT inhibitors (NAMPTi) tested before were discontinued due to toxicity; however, a novel NAMPTi, KPT-9274, is a promising, low-toxicity option currently in clinical trials.

Comparative hepatotoxicity of novel lithium bis(trifluoromethanesulfonyl)imide (LiTFSI, ie. HQ-115) and legacy Perfluorooctanoic acid (PFOA) in male mice: Insights into epigenetic mechanisms and pathway-specific responses.

Lithium Bis(trifluoromethanesulfonyl)imide (LiTFSI ie. HQ-115), a polymer electrolyte used in energy applications, has been detected in the environment, yet its health risks and environmental epigenetic effects remain unknown. This study aims to unravel the potential health risks associated with LiTFSI, investigate the role of DNA methylation-induced toxic mechanisms in its effects, and compare its hepatotoxic impact with the well-studied Perfluorooctanoic Acid (PFOA). Using a murine model, six-week-old male CD1 mice were exposed to 10 and 20 mg/kg/day of each chemical for 14 days as 14-day exposure and 1 and 5 mg/kg/day for 30 days as 30-day exposure. Results indicate that PFOA exposure induced significant hepatotoxicity, characterized by liver enlargement, and elevated serum biomarkers. In contrast, LiTFSI exposure showed lower hepatotoxicity, accompanied by mild liver injuries. Despite higher bioaccumulation of PFOA in serum, LiTFSI exhibited a similar range of liver concentrations compared to PFOA. Reduced Representative Bisulfite Sequencing (RRBS) analysis revealed distinct DNA methylation patterns between 14-day and 30-day exposure for the two compounds. Both LiTFSI and PFOA implicated liver inflammatory pathways and lipid metabolism. Transcriptional results showed that differentially methylated regions in both exposures are enriched with cancer/disease-related motifs. Furthermore, Peroxisome proliferator-activated receptor alpha (PPARα), a regulator of lipid metabolism, was upregulated in both exposures, with downstream genes indicating potential oxidative damages. Overall, LiTFSI exhibits distinct hepatotoxicity profiles, emphasizing the need for comprehensive assessment of emerging PFAS compounds.