Undesirable Symptoms Research Articles

FERMENTABLE OLIGOSACCHARIDES, DISACCHARIDES, MONOSACCHARIDES AND POLYOLS AND THEIR ROLE IN FOOD DIGESTION

Oligosaccharides containing fructose (fructans, inulin), galactose (galactans, stachyose, raffinose), disaccharides enclosing galactose (lactose), monosaccharides and mixtures of monosaccharides encompassing fructose (fruit sugar, honey) and saccharide polyols (mannitol, malbitol, sorbitol), are considered as safe to be consumed and beneficial to health. Gradually, however, their presence in the human diet reaches amounts that are indigestible by the small intestine, causing an osmotic load on the intestinal lumen. Subsequently, they pass into the large intestine, where they are fermented by intestinal bacteria to undesirable products such as gaseous carbon dioxide, hydrogen, methane, sulfane, and short chain fatty acids. Indigestible fermentable oligosaccharides, disaccharides, monosaccharides, and polyols may cause undesirable symptoms such as an increased flatulence, bloating, abdominal pain, alterations to the intestinal physiology, cessation of peristalsis, or diarrhea, which are manifested by a wide array of diseases of the gastrointestinal tract, such as the irritable bowel syndrome or small intestinal bacterial overgrowth. Fruits, vegetables, dairy products, legumes, some cereals, as well as honey or various sweeteners are among the most common food sources of these carbohydrates.

\u201cIt\u2019s called overamping\u201d: experiences of overdose among people who use methamphetamine

BackgroundThe USA is experiencing increases in methamphetamine use and methamphetamine-related or attributed deaths. In the current study, we explore qualitative narratives of methamphetamine overdose and strategies used by people who use drugs to reduce the undesirable effects associated with methamphetamine use.MethodsWe conducted 21 qualitative interviews with people over the age of 18 who reported using methamphetamine in the previous 3 months in Nevada and New Mexico. Interviews were recorded, transcribed, and analyzed using qualitative thematic analysis.ResultsRespondents described a constellation of psychological and physical symptoms that they characterized as “overamping,” experienced on a continuum from less to more severe. Reports of acute, fatal methamphetamine overdose were rare. Few reported seeking medical attention for undesirable effects (usually related to psychological effects). General self-care strategies such as sleeping and staying hydrated were discussed.ConclusionsWhen asked directly, our respondents claimed that acute, fatal methamphetamine overdose is rare or even impossible. However, they described a number of undesirable symptoms associated with overconsumption of methamphetamine and had few clinical or harm reduction strategies at their disposal. Addressing this current wave of drug-related deaths will require attention to the multiple factors that structure experiences of methamphetamine “overdose,” and a collaborative effort with PWUDs to devise effective harm reduction and treatment strategies.

THE ANALYSIS OF THE IMPACT OF THE TYPE OF CONTRACEPTION USED BY WOMEN ON THE LEVEL OF THEIR SEXUAL SATISFACTION AND COMFORT OF USE.

The aim: To compare satisfaction of women using oral contraception to satisfaction of women using the levonorgestrel-secreting intrauterine system. In the comparison the following factors were taken into account: comfort of use, menstrual cycle, libido level, well-being and the impact on the relationship with a partner. Materials and methods: The study involved 129 randomly selected women who had to fill in the research survey questionnaire. Results: It has been proved that patients are more willing to use the intrauterine system secreting levonorgestrel because of a more reliable contraceptive effect and convenience of use. This kind of contraception has a beneficial effect on libido and relationships with a partner. Women using oral contraception did not report such advantageous influence of their method of contraception. An increase in libido was noticed for 24 women in the group of patients using the levonorgestrel-secreting intrauterine system and for 8 women in the group of users of oral contraception, which corresponds to 33.8% and 13.8%. Patients used oral contraception more often in order to regulate their menstrual cycle and to reduce heavy menstrual bleeding. Conclusions: The study identifies groups of women for whom a specific method of contraception would be appropriate. The greatest benefits of using the levonorgestrel-secreting intrauterine system will have patients who appreciate the convenience of use, as well as those who have sex drive disorders or for whom oral contraception causes undesirable symptoms. Women with hormonal disorders, irregular menstrual cycles and heavy menstrual bleeding will benefit most from the use of oral contraception.

A Prospective study for effect of wound or scar tissue massage after thyroidectomy on neck discomfort and voice change

Objectives: This study aimed to found and selecting the causes behind neck discomfort and change in the voice following thyroidectomy and to determine the efficacy of wound massaging technique on decreasing and relief such symptoms. Methods: Totally 55 patients all females who underwent thyroidectomy were included in our study, the patients were divided in to two groups (26 in the experimental group and 29 in the control group). The massaging technique was instructed to all patients in the experimental group 1 week postoperatively and the feedback were received from patients after 2 weeks and 4 weeks from instruction time. The analysis was achieved for both groups of patients. Results: After exclusion of laryngeal pathologies post operatively. The recovery rate of the patients in the experimental group from post operation adhesions was obviously and significantly much more better recovery from subjective voice impairment score (SVIS) and neck discomfort score (NDS) which was represented by swallowing impairment score (SIS). (all P < 0.01) in compare with the patients in control group. Those results indicates that localized adhesions following total thyroidectomy operation could be included in affection of general movement as well as vertical movements of the larynx and the wound massaging technique might help patients recovering the normal general movement of the larynx postoperatively. Conclusion: Discomfort of the neck, pulling neck sensation, and voice or phonation changes after total thyroidectomy surgery might due to local surgical adhesions of the wound which possibly accompanied with impairment of vertical movement of larynx. so, releasing of such adhesions could help the patients to recover much more quickly from mentioned undesirable symptoms postoperatively and start their normal daily activities.

The use of music at home reduces symptoms of dementia and caregiver distress

AbstractBackgroundAs Alzheimer’s disease progresses, neuropsychiatric symptoms, particularly those common in the middle stages of the disease can be increasingly stressful for family caregivers. Music‐based interventions, when personalized and added to daily caregiving routines, have been shown to reduce occurrences or severity of these undesirable symptoms. In this study, family caregivers learned to implement music interventions to mitigate the impact of challenging behaviors.MethodWe present the results of interim analyses of the results for the first group of participants in a study of a psychoeducational, music‐based intervention for family caregivers. Eighteen NYC‐based family caregivers participated in a 6‐week program either in person (pre‐COVID) or online with a music therapist. Following each weekly one‐hour workshop, caregivers were asked to utilize music interventions such as singing during care, listening to personalized playlists on Spotify, or facilitating music and movement with their care recipient. The Neuropsychiatric Inventory‐Questionnaire was used to measure twelve neuropsychiatric domains and measure caregiver distress before and after the 6‐week intervention. Paired sample t‐tests were used to measure change in these outcomes for caregiver and care recipient. A Pearson correlation coefficient was used to estimate the relationship between symptoms of dementia and caregiver distress.ResultsThere was a significant improvement in both neuropsychiatric domains in care recipients from before (M= 12.23 ± 6.26) the six‐week program to after (7.83 ± 3.51), p =.028, and in caregiver distress prior (M=14.88 ± 9.36) to after (8.68 ± 5.95), p =.03. The symptoms most reported to contribute to caregiver distress were irritability (n=12), night‐time behaviors (n=12), and agitation (n=11). Neuropsychiatric symptoms and caregiver distress were found to be strongly correlated, r (16) =.64, p=.004.ConclusionPreliminary results of this ongoing study indicate that caregivers who implement music‐based interventions can both reduce undesirable symptoms of dementia and thereby their own distress.

Reduction of behavioural inhibition disorders in behavioural variant frontotemporal dementia patients observed under semi‐ecological conditions

AbstractBackgroundBehavioural variant frontotemporal dementia (bvFTD) is characterised by a progressive deterioration of personality, social conduct and cognition. Especially, inhibition troubles are reported, impairing the daily lives of patients and caregivers. However, assessment and characterisation of disinhibition are still poorly known, leading to a limited management of these disorders. We aim to identify activities related to an increase or a decrease of behavioural disinhibition, in order to better apprehend these disorders and set up non‐pharmacological approaches to limit these troubles.MethodWe assess behavioural disinhibition in a semi‐ecological setting, noting occurrences of 16 behaviours – derived from clinical criteria of bvFTD – related to compulsivity, impulsivity or social disinhibition, in a population of 25 bvFTD and 25 healthy controls (HC). Subjects are placed in a waiting room during 45 minutes, instructions are to get comfortable and enjoy the room. During the scenario, they are firstly free to explore the room (Free Phase) and are then guided by a questionnaire to be filled in (Guided Phase). Duration of activity related behaviours and motor patterns are also collected to look for correlations with behavioural disinhibition scores.ResultTo date, we included 22 bvFTD and 24 HC. We found out that disinhibition behaviours are not constant during the scenario. BvFTD patients are less impulsive during the guided phase compared to the free phase (p=0.014, Wilcoxon test), and show more social disinhibition than HC during the free phase and at the end of the guided phase (p=0.014 and p=0.026 respectively, Mann‐Whitney U tests), but not during the guided phase. Compulsive behaviours remain unchanged. Moreover, looking for correlations between behavioural disinhibition and activity related behaviours or motor patterns, we found out that: 1) social disinhibition would be less present during activity (eg, reading), 2) there would be less compulsivity when patients are dealing with the questionnaire, and 3) impulsivity would increase during exploration of the room (eg, books).ConclusionThis study relying on a semi‐ecological setting highlights interesting areas for non‐pharmacological treatments of behavioural disturbances in bvFTD, consistent with previous studies encouraging concentration on a given task, hobbies or a tidy environment to reduce undesired behavioural symptoms in dementia.

Beneficial and Detrimental Effects of Antioxidants Use in Sports: How is it Balanced?

This review aims to summarize the fundamental classes of antioxidants, the utilization of the supplement with antioxidants as ergogenic benefits in exercise and sport, the efficiency, and the consequence of their chronic uses. Antioxidants have been used for a long time in different sports disciplines and at all degrees of rivalry. The supplement with antioxidants anticipates muscle damage by reducing immune dysfunction, inflammation, and fatigue syndrome for athletes. Subsequently, antioxidant supplementation will improve the physical performances and health of athletes. Polyphenol compounds as incredible antioxidants that are abundant in numerous plants. The consumption of antioxidants could be hazardous whenever taken in high dosages. Researchers found that overdoses may cause undesirable symptoms and might grow the risk of death.

Drug delivery to the inflamed intestinal mucosa - targeting technologies and human cell culture models for better therapies of IBD.

Current treatment strategies for inflammatory bowel disease (IBD) seek to alleviate the undesirable symptoms of the disorder. Despite the higher specificity of newer generation therapeutics, e.g. monoclonal antibodies, adverse effects still arise from their interference with non-specific systemic immune cascades. To circumvent such undesirable effects, both conventional and newer therapeutic options can benefit from various targeting strategies. Of course, both the development and the assessment of the efficiency of such targeted delivery systems necessitate the use of suitable in vivo and in vitro models representing relevant pathophysiological manifestations of the disorder. Accordingly, the current review seeks to provide a comprehensive discussion of the available preclinical models with emphasis on human in vitro models of IBD, along with their potentials and limitations. This is followed by an elaboration on the advancements in the field of biology- and nanotechnology-based targeted drug delivery systems and the potential rooms for improvement to facilitate their clinical translation.

Abstract 1200: Long-duration term TTFields treatment of glioblastoma cells induces cell death

Abstract Glioblastoma is the most aggressive among brain tumors. Radiotherapy and chemotherapy, as adjuvanttreatments after surgical removal of the tumor mass, are often accompanied by undesirable symptoms. Evenwith these available treatment options, patient prognosis is extremely poor. The only approved treatmentoption demonstrating improved life expectancy in the last twenty years has been the application of TumorTreating Fields (TTFields). However, despite different therapeutic actions, tumor relapse occurs inexorably inmost patients. It is essentially unanimously agreed upon that tumor recurrence is due to a small populationof cells named glioblastoma stem cells (GSCs). GSCs represent a restricted cellular subpopulation in the tumormass composed mainly of bulk cells. The main characteristic of GSCs is their tumorigenic capacity even if asmall number of cells are left after surgery. Our working hypothesis is based on evidence that TTFieldsexposure destabilizes the mitotic spindle of rapidly dividing cells to elicit cell death. Thus, TTFields stimulationshould preferentially target bulk cells due to their higher proliferation rates compared to GSCs. Preliminaryexperiments performed using glioblastoma primary cultures obtained from patients' biopsies demonstratedthe presence of two different cell populations. In glioblastoma primary cultures maintained in stem-cellselective medium, more than 90% of glioblastoma cells did not exhibit stemness characteristics. After 72hours of TTFields stimulation, cell death was ascertained in approximately 50% of cells. The remaining viablecells were more than 20% positive for three different stemness markers. Long duration TTFields treatmentexperiments (144 and 288 hours) showed that TTFields at 200 kHz is able to increase the percentage of GSCin glioblastoma cells, yet did exhibit a propensity to reestablish cellular proliferation.In conclusion, long duration TTFields (200 kHz) treatment demonstrated efficacy by inducing cell death anddelaying glioblastoma cell expansion. However, to prevent glioblastoma relapse it is important to combineTTFields with different combination partners that specifically target glioblastoma stem cells. Citation Format: Stefania Castiglione, Matteo Ranucci, Gaetano Cannavale, Francesca Cianci, Ivan Verduci, Michele Mazzanti. Long-duration term TTFields treatment of glioblastoma cells induces cell death [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1200.

Association Between Postoperative Vertigo and Hearing Outcomes After Stapes Surgery for Otosclerosis

During the postoperative period, most patients with otosclerosis report vertigo and/or nausea caused by interventions within the inner ear. The aim of this study was to evaluate both early and late vertigo associated with hearing improvement after stapes surgery for otosclerosis. The analysis included 170 patients admitted to the hospital undergoing their first surgery for otosclerosis. Audiological diagnostics, surgical techniques, and symptoms reported by the patients were all analyzed. A statistical correlation and an unfavorable influence of late, undesired symptoms, such as vertigo, nausea/vomiting, and nystagmus, on final hearing improvement after surgical treatment of otosclerosis were found. Prostheses that were too long or placed too deep within the inner ear space were the most frequent cause of both vertigo and lack of hearing improvement observed after stapedotomy. A significant negative influence on bone conduction thresholds, particularly at 2000 Hz, was associated with vestibular symptoms persisting for 7 days after the surgery. Symptoms of impaired bony labyrinth function after stapedotomy, persisting for more than 1 year, were associated with insufficient reduction of the air-bone gap and worse improvement in bone conduction thresholds at 1000 and 2000 Hz. The cause of both problems was related to a prosthesis that was too long or placed too deep in the inner ear during stapedotomy.

Estrogenic Plants: to Prevent Neurodegeneration and Memory Loss and Other Symptoms in Women After Menopause.

In mammals, sexual hormones such as estrogens play an essential role in maintaining brain homeostasis and function. Estrogen deficit in the brain induces many undesirable symptoms such as learning and memory impairment, sleep and mood disorders, hot flushes, and fatigue. These symptoms are frequent in women who reached menopausal age or have had ovariectomy and in men and women subjected to anti-estrogen therapy. Hormone replacement therapy alleviates menopause symptoms; however, it can increase cardiovascular and cancer diseases. In the search for therapeutic alternatives, medicinal plants and specific synthetic and natural molecules with estrogenic effects have attracted widespread attention between the public and the scientific community. Various plants have been used for centuries to alleviate menstrual and menopause symptoms, such as Cranberry, Ginger, Hops, Milk Thistle, Red clover, Salvia officinalis, Soy, Black cohosh, Turnera diffusa, Ushuva, and Vitex. This review aims to highlight current evidence about estrogenic medicinal plants and their pharmacological effects on cognitive deficits induced by estrogen deficiency during menopause and aging.

Viewing personalized video clips recommended by TikTok activates default mode network and ventral tegmental area

Cutting-edge recommendation algorithms have been widely used by media platforms to suggest users with personalized content. While such user-specific recommendations may satisfy users’ needs to obtain intended information, some users may develop a problematic use pattern manifested by addiction-like undesired behaviors. Using a popular video sharing and recommending platform (TikTok) as an example, the present study first characterized use-related undesired behaviors with a questionnaire, then investigated how personally recommended videos modulated brain activity with an fMRI experiment. We found more undesired symptoms were related to lower self-control ability among young adults, and about 5.9% of TikTok users may have significant problematic use. The fMRI results showed higher brain activations in sub-components of the default mode network (DMN), ventral tegmental area, and discrete regions including lateral prefrontal, anterior thalamus, and cerebellum when viewing personalized videos in contrast to non-personalized ones. Psychophysiological interaction analyses revealed stronger coupling between activated DMN subregions and neural pathways underlying auditory and visual processing, as well as the frontoparietal network. This study highlights the functional heterogeneity of DMN in viewing personalized videos and may shed light on the neural underpinnings of how recommendation algorithms are able to keep the user's attention to suggested contents.

Effect of Wearing Face Masks on the Carbon Dioxide Concentration in the Breathing Zone

The use of face masks is among the measures taken to prevent person-to-person transmission of the virus (SARS-CoV-2) responsible for the coronavirus disease (COVID-19). Lately, concern was expressed about the possibility that carbon dioxide could build up in the mask over time, causing medical issues related to the respiratory system. In this study, the carbon dioxide concentration in the breathing zone was measured while wearing a surgical mask, a KN95 and a cloth mask. For the surgical mask, the concentration was determined under different conditions (office work, slow walking, and fast walking). Measurements were made using a modified indoor air quality meter equipped with a nondispersive infrared (NDIR) CO2 sensor. Detected carbon dioxide concentrations ranged from 2150 ± 192 to 2875 ± 323 ppm. The concentrations of carbon dioxide while not wearing a face mask varied from 500–900 ppm. Doing office work and standing still on the treadmill each resulted in carbon dioxide concentrations of around 2200 ppm. A small increase could be observed when walking at a speed of 3 km h–1 (leisurely walking pace). Walking at a speed of 5 km h–1, which corresponds to medium activity with breathing through the mouth, resulted in an average carbon dioxide concentration of 2875 ppm. No differences were observed among the three types of face masks tested. According to the literature, these concentrations have no toxicological effect. However, concentrations in the detected range can cause undesirable symptoms, such as fatigue, headache, and loss of concentration.

COVID-19 Vaccination Outcomes Among Breastfeeding Woman and Their Children – a Pharmacovigilance Survey Research

Background: The scarcity of data on Covid-19 vaccination among lactating women raises concern about the safety of vaccines in this group of patients. Lactating individuals who decided to get vaccinated participated in our pharmacovigilance survey research. We present a profile of adverse events reported among these women and their children. Methods: We conducted a cross-sectional survey among breastfeeding women who had received COVID-19 vaccines. Participants were recruited through social media and websites. We examined the frequency of adverse events among breastfeeding women, their children and impact on breastfeeding. Statistical analysis included chi-square tests and logistic regression. Findings: We included 702 breastfeeding mothers. 486 mothers were vaccinated with Pfizer, 83 with Moderna, 95 with AstraZeneca, and 38 with Johnson & Johnson’s Janssen vaccine. 7·1% mothers reported adverse reactions among their children, most of which were mild. 95·9% mothers did not observe any impact on milk supply, 2·4% observed decreased and 1·7% observed increased milk supply. Statistical analysis showed that the occurrence of undesirable symptoms in children had not been related to the number of vaccine doses taken by the mother, the type of vaccine or the age of the child. Interpretation: Maternal vaccination during lactation might affect some breastfed babies and milk supply in some women, but in most there will be no noticeable effect. These outcomes might not be related to the specific vaccine. Our study supports the statement that the benefits of maternal vaccination during lactation outweigh the risks.Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: The Bioethics Commission of the Medical University of Poznan determined that the study was exempt from the review.

Efficacy and safety of antipsychotics in adolescents with an acute psychotic episode in relation to the activity of CYP3A and CYP2D6 isoenzymes

Antipsychotics are a first-line treatment for psychotic disorders. The cytochrome P450 isoenzymes CYP3A4/5 and CYP2D6 metabolize most antipsychotics. The activity of these isoenzymes in children changes with maturation, so it is different from that in adults. Objective: to study the associations of CYP3A and CYP2D6 isoenzyme activity parameters with the efficacy and safety of antipsychotics in adolescents with an acute psychotic episode. Patients and methods. The investigation enrolled 53 adolescents with an acute psychotic episode who took antipsychotics. The observation period lasted 14 days. The CGAS, PANSS, UKU SERS, SAS, and BARS scales were used to evaluate the efficiency and safety of the therapy on day 14. The activity of CYP3A and CYP2D6 isoenzymes was measured by determining the metabolic ratios of the concentrations of endogenous substrates of the isoenzymes and their metabolites in a morning urine sample on days 1 and 14 of the study. The activity of CYP3A was assessed by the 6-beta hydroxycortisol/cortisol ratio; that of CYP2D6 was measured by the 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline/pinoline ratio. The influence of carriage of polymorphic variants CYP2D6*4,*9,*10, CYP3A4*22, CYP3A5*3 on the activity of isoenzymes was excluded by removing their carriers from the analysis. Results and discussion. The investigators revealed an association of certain antipsychotic-induced undesirable symptoms with CYP3A and CYP2D6 activity parameters. On day 1, a lower CYP2D6 activity was initially observed in patients with tremor (0.54 [0.34; 1.34] vs 1.25 [0.91; 1.75]; p=0.023). Also, patients with any documented adverse reaction (ARs) to therapy had initially a decreased CYP3A activity (1.2 [0.85; 2.29] vs 2.55 [1.44; 4.83]; p=0.047) and an enhanced CYP3A activity during therapy (the activity difference between day 14 and day 1 was 0.28 [-0.28; 2.32] vs -1.3 [-3.47; 0.66]; p=0.042). Conclusion. The initially reduced activity of CYP2D6 and CYP3A isoenzymes is a significant predictor of antipsychotic-induced ARs in adolescents with an acute psychotic episode. The predictive role of CYP2D6 and CYP3A activity levels in the efficacy of antipsychotics has not been confirmed.

The incidence of severe oral mucositis and its occurrence sites in pediatric oncologic patients.

Background Childhood cancer is one of the main causes of child mortality and its treatment has debilitating effects on the oral cavity. Several oral mucositis (SOM) is one of the most common and may cause undesirable symptoms such as pain and risk of systemic infection.Material and Methods This was a longitudinal, retrospective, and observational study determining the incidence of severe oral mucositis (SOM) and its occurrence sites in pediatric oncologic patients, in João Pessoa, Brazil, between 2013 and 2018. Data from 56 patients aged 1 to 18 years were collected from their medical records and through an oral mucosa examination, from the 1st to 5th week of chemotherapy treatment (CT) using the modified Oral Assessment Guide, by previously calibrated examiners (Kappa index > 0.7). The data were analyzed by the Chi-square test, and Odds Ratios were calculated.Results Most patients were females (54.5%), aged 8.8 years (± 4.8), with hematologic tumors (73.2%), predominantly Acute Lymphoid Leukemia (50.0%). An increase in the occurrence of SOM was observed throughout the CT (P = 0.05), ranging from 12.5% in the 1st to 35.7% in the 5th CT week. In the 1st CT week, there was a predominance of alterations in the lips (5.5%) and saliva (5.5%), while in the 5th, the jugal / palate mucosa (21.4%) remained the most affected site by SOM. Differences in the severity of SOM in the jugal / palate mucosa (P = 0.01) and labial mucosa (P = 0.04) were observed over time. In the 5th CT week, the likelihood of developing SOM was 13.3-fold higher (95% CI: 1.5 - 105.6) in patients with hematologic tumors.Conclusions The incidence of SOM was higher in the 5th CT week, most commonly affecting the jugal / palate mucosa, and patients with hematologic tumors were more prone to develop SOM. Key words:Mucositis, oncology, pediatric dentistry.

STEM-10. LONG-LASTING TUMOR TREATING FIELDS (TTFIELDS) STIMULATION OF GLIOBLASTOMA PRIMARY CULTURE DAMAGES PREFERENTIALLY FULLY DIFFERENTIATED CANCER CELLS

Abstract Glioblastoma (GBM) is the most aggressive among brain tumors. Radiotherapy and chemotherapy as adjuvant procedures after surgical removal of the tumor mass, are often accompanied by undesirable symptoms and result in an extremely poor prognosis. In the last twenty years, it has been demonstrated that the only treatment able to improve the life expectancy of patients with GBM has been Tumor Treating Fields (TTFields) application. However, despite different therapeutic actions, tumor relapse occurs inexorably in most of the patients. There is scientific consensus that tumor recurrence is due to a population of cells named GBM stem cells (GSCs). GSCs represent a restricted subpopulation in the tumor mass, which is mainly composed of bulk cells. The main characteristic of GSCs is their tumorigenic potential even if a small number of cells are left after surgery. Our working hypothesis is based on the evidence that TTFields destabilize the mitotic spindle of dividing cells. Thus, TTFields stimulation should preferentially target bulk cells because of their higher proliferation rate compared to GSCs. Preliminary experiments performed using GBM primary cultures obtained from patients’ biopsies confirmed the presence of two different cell populations. In GBM, primary cultures maintained in stem-cell permissive medium, more than 70% of cells do not show stemness properties. After 72 hours of TTFields stimulation, almost 50% of the cells die. The remaining cells were more than 50% positive for CD44, SOX2, OCT4, and Nanog stemness markers, suggesting an enrichment of GSCs within the population. Following long lasting stimulation (up to 288 hours), GSCs percentage further increased and, more importantly, cells restored their ability to proliferate. In conclusion, TTFields treatment demonstrated efficacy by delaying GBM expansion. However, to prevent GBM relapse, it is imperative to increase the inhibitory efficiency of TTFields, specifically on GBM stem cell growth.

The Neutrophil: Constant Defender and First Responder

The role of polymorphonuclear neutrophils (PMNs) in biology is often recognized during pathogenesis associated with PMN hyper- or hypo-functionality in various disease states. However, in the vast majority of cases, PMNs contribute to resilience and tissue homeostasis, with continuous PMN-mediated actions required for the maintenance of health, particularly in mucosal tissues. PMNs are extraordinarily well-adapted to respond to and diminish the damaging effects of a vast repertoire of infectious agents and injurious processes that are encountered throughout life. The commensal biofilm, a symbiotic polymicrobial ecosystem that lines the mucosal surfaces, is the first line of defense against pathogenic strains that might otherwise dominate, and is therefore of critical importance for health. PMNs regularly interact with the commensal flora at the mucosal tissues in health and limit their growth without developing an overt inflammatory reaction to them. These PMNs exhibit what is called a para-inflammatory phenotype, and have reduced inflammatory output. When biofilm growth and makeup are disrupted (i.e., dysbiosis), clinical symptoms associated with acute and chronic inflammatory responses to these changes may include pain, erythema and swelling. However, in most cases, these responses indicate that the immune system is functioning properly to re-establish homeostasis and protect the status quo. Defects in this healthy everyday function occur as a result of PMN subversion by pathological microbial strains, genetic defects or crosstalk with other chronic inflammatory conditions, including cancer and rheumatic disease, and this can provide some avenues for therapeutic targeting of PMN function. In other cases, targeting PMN functions could worsen the disease state. Certain PMN-mediated responses to pathogens, for example Neutrophil Extracellular Traps (NETs), might lead to undesirable symptoms such as pain or swelling and tissue damage/fibrosis. Despite collateral damage, these PMN responses limit pathogen dissemination and more severe damage that would otherwise occur. New data suggests the existence of unique PMN subsets, commonly associated with functional diversification in response to particular inflammatory challenges. PMN-directed therapeutic approaches depend on a greater understanding of this diversity. Here we outline the current understanding of PMNs in health and disease, with an emphasis on the positive manifestations of tissue and organ-protective PMN-mediated inflammation.

An Integrative Review of the Symptom Perception Process in Heart Failure.

Accurate symptom perception is a fundamentally essential component of self-care for patients with heart failure (HF) so they can make appropriate decisions about their symptoms. The purpose of this integrative review was to describe the pathways of the symptom perception process and its contributing factors in patients with HF. A comprehensive literature search was conducted using PubMed, EMBASE, and PsycINFO databases to identify studies describing the symptom perception process (symptom detection, comprehension, and response) in adult patients with HF. Two pathways of the symptom perception process were identified from 42 articles: ideal and undesirable pathways. Patients in the ideal symptom perception pathway had a comprehensive understanding of HF and a firm belief in the importance of self-care, were vigilant, and possessed good decision-making skills. They also were able to successfully use their experiences for future care. However, patients in the undesirable symptom perception pathway had a limited understanding of HF with poor symptom monitoring skills and inaccurate judgments about symptoms. Diverse factors contributing to the symptom perception process were identified (eg, levels of understandings of HF and social support). Our review indicated that symptom perception was likely to diversify the pathway of HF management. A variety of contributing factors to the symptom perception process were found to be intertwined. The findings of our review can inform the development of best patient education practice, although further research needs to be conducted to understand why and how patients can follow the most appropriate path from their past experiences.

Abstract 4374: CE+BZA combination therapy decreases breast cancer outgrowth in part through activation of the AHR pathway

Abstract Menopause occurs in all women, usually between the ages of 45 and 55. As a result of menopause, women often experience undesirable vasomotor symptoms, which can be alleviated by hormone replacement therapy (HRT). The Women's Health Initiative (WHI) trial concluded that PremPro, a HRT formulation that combines conjugated equine estrogens (CE) with medroxyprogesterone acetate, increases the risk of breast cancer. Over the years, the number of women taking HRT has dramatically decreased due to the perceived risk based largely on the results of the WHI trial. Follow-up studies suggest that breast cancer cases from PremPro treatment were primarily due to the outgrowth of occult tumors, not the formation of new disease. Duavee, a more recent form of HRT that combines CE and bazedoxifene (BZA), a selective estrogen receptor modulator (SERM) and degrader (SERD), has been approved by the FDA for treatment of moderate to severe hot flashes and to reduce the risk of osteoporosis. More importantly, this CE+BZA mixture not only relieves symptoms associated with menopause, but it also does not stimulate the breast or uterus. Several preclinical studies suggest that CE+BZA might be protective in the breast, however the mechanism of action of this new combination therapy is not known. Our goal, therefore, was to elucidate the underlying molecular mechanisms by which CE+BZA differentially affects estrogen receptor alpha (ERα) action in the mammary gland. Pathway analysis from RNA-sequencing revealed Aryl Hydrocarbon Receptor (AHR) signaling as the top canonical pathway affected by treatment with CE+BZA. Previous studies reported that 4-hydroxytamoxifen, a metabolite of the SERM tamoxifen, was able to activate the AHR pathway. In our study we determined that BZA treatment activated the AHR pathway in both ERα-positive and ERα-negative cell lines. BZA increased expression of aryl hydrocarbon receptor repressor (AHRR) in cell lines and increased expression of two AHR pathway members, CYP1A1 and CYP1B1, in tumors of estrogen-sensitive polyoma middle T antigen (PyMT) mice. AHRR has been reported to act as a tumor suppressor in breast cancer; therefore activation of AHR by BZA in women taking CE+BZA combination therapy might be one mechanism by which outgrowth of occult tumors is decreased. Further evaluation of the role of AHR in breast cancer is necessary to improve our understanding of CE+BZA action. Citation Format: Anna G. Dembo, Emily S. Aledort, Geoffrey L. Greene. CE+BZA combination therapy decreases breast cancer outgrowth in part through activation of the AHR pathway [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4374.