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Abstract Background Malnutrition is a prevalent and hard-to-treat condition in older adults. enteral feeding is common in acute and long-term care. Data regarding the prognosis of patients receiving enteral feeding in geriatric medical settings is lacking. Such data is important for decision-making and preliminary instructions for patients, caregivers, and physicians. This study aimed to evaluate the prognosis and risk factors for mortality among older adults admitted to a geriatric medical center receiving or starting enteral nutrition (EN). Methods A cohort retrospective study, conducted from 2019 to 2021. Patients admitted to our geriatric medical center who received EN were included. Data was collected from electronic medical records including demographic, clinical, and blood tests, duration of enteral feeding, Norton scale, and Short Nutritional Assessment Questionnaire score. Mortality was assessed during and after hospitalization. Data were compared between survivors and non-survivors. Multivariate logistic regressions were performed to identify the variables most significantly associated with in-hospital mortality. Results Of 9169 patients admitted, 124 (1.35%) received enteral feeding tubes. More than half of the patients (50.8%) had polypharmacy (over 8 medications), 62% suffered from more than 10 chronic illnesses and the majority of patients (122/124) had a Norton scale under 14. Most of the patients had a nasogastric tube (NGT) (95/124) and 29 had percutaneous endoscopic gastrostomies (PEGs). Ninety patients (72%) died during the trial period with a median follow-up of 12.7 months (0.1–62.9 months) and one-year mortality was 16% (20/124). Associations to mortality were found for marital status, oxygen use, and Red Cell Distribution Width (RDW). Age and poly-morbidity were not associated with mortality. Conclusion In patients receiving EN at a geriatric medical center mortality was lower than in a general hospital. The prognosis remained grim with high mortality rates and low quality of life. This data should aid decision-making and promote preliminary instructions.

BackgroundNursing care residents have high hospitalization rates. To address this, we established a unique virtual geriatric unit that has developed a program aimed at providing support to nursing homes.AimsWe aimed to evaluate effectiveness of in-house intravenous antibiotic treatment in nursing hospitals after the implementation of the specially designed training program.MethodsA cohort study of nursing home residents to evaluate a training program for providers, designed to increase awareness and give practical tools for in-house treatment of acute infections. Data obtained included types of infections, antibiotics used, hospital transfer, and length of treatment. Primary outcomes were in-house recovery, hospitalization and mortality. Univariate analysis and multivariable logistic regression analysis to assess association between different factors and recovery.ResultsA total of 890 cases of acute infections were treated with intravenous antibiotics across 10 nursing homes over a total of 4,436 days. Of these cases, 34.8% were aged 90 years or older. Acute pneumonia was the most prevalent infection accounted for 354 cases (40.6%), followed by urinary tract infections (35.7%), and fever of presumed bacterial infection (17.1%). The mean duration of intravenous antibiotic treatment was 5.09 ± 3.86 days. Of the total cases, 800 (91.8%) recovered, 62 (7.1%) required hospitalization and nine (1.0%) resulted in mortality. There was no significant difference observed in recovery rates across different types of infections.DiscussionAppling a simple yet unique intervention program has led to more “in-house” residents receiving treatment, with positive clinical results.ConclusionTreating in-house nursing home residents with acute infections resulted in high recovery rates. Special education programs and collaboration between healthcare organizations can improve treatment outcomes and decrease the burden on the healthcare system.

Galina Plotnikov,1,2 Saleh Sharif,2,3 Gleb Buturlin,2 Inbal Segal,1 Oleg Gorelik,2 Nadya Kagansky2,4 1Geriatric Assessment Unit, Yitzhak Shamir Medical Center, Zerifin, 7033001, Israel; 2Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel; 3Department of Internal Medicine C, Yitzhak Shamir Medical Center, Zerifin, 7033001, Israel; 4Shmuel Harofe Geriatric Medical Center, Beer Yaakov, IsraelCorrespondence: Galina Plotnikov, Geriatric Assessment Unit, Yitzhak Shamir Medical Center, Zerifin, 7033001, Israel, Tel +972-8-9542271, Fax +972-8-9779597, Email galina.plotnikov@gmail.comPurpose: To evaluate demographic, clinical, and laboratory variables, and their associations with in-hospital mortality, among elderly internal medicine patients with nasogastric tube (NGT) feeding.Patients and Methods: Demographic, clinical, and laboratory data were collected retrospectively for 129 patients aged ≥ 80 years who initiated NGT feeding during their hospitalization in internal medicine wards. The data were compared between survivors and non-survivors. Multivariate logistic regressions were performed to identify the variables most significantly associated with in-hospital mortality.Results: The in-hospital mortality rate was 60.5%. Compared to survivors, non-survivors more often presented with pressure sores (P=0.005) and lymphopenia (P< 0.001), were more often treated with invasive mechanical ventilation (P< 0.001), and less often underwent geriatric assessment (P< 0.001). Non-survivors demonstrated higher mean levels of C-reactive protein, and lower mean values of serum cholesterol, triglycerides, total protein, and albumin (P< 0.001 for all comparisons). On multivariate analysis, the following variables were most significantly associated with in-hospital mortality in the entire cohort: the presence of pressure sores (odds ratio [OR], 4.34; 95% confidence interval [CI], 1.68– 11.48; P=0.003) and lymphopenia (OR, 4.09; 95% CI, 1.51– 11.08; P=0.006), and serum cholesterol (OR, 0.98; 95% CI, 0.96– 0.99; P=0.003).Conclusion: Among elderly acutely ill patients who initiated NGT feeding during hospitalization, in-hospital mortality was extremely high. The factors most strongly associated with in-hospital mortality were the presence of pressure sores and lymphopenia, and lower serum cholesterol levels. These findings may provide useful prognostic information for decision-making regarding initiation of NGT feeding in elderly hospitalized patients.Keywords: aging, enteral feeding, hospitalization, prognosis

The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are simple markers of systemic inflammatory responses. It has been previously suggested that they can predict COVID-19 severity. Age and frailty may also influence their values. This study aimed to evaluate the impact of COVID-19 severity versus age and frailty on NLR and PLR values. This was a retrospective, observational two cohorts’ comparative study. The first cohort is comprised of patents positive for SARS-CoV-2, with mild or asymptomatic disease, admitted to designated COVID-19 departments in a large geriatric medical center (GMC). The second included patients with COVID-19 admitted to designated COVID-19 departments in a large general hospital for symptomatic disease from March 2020 to March 2021. We compared baseline characteristics including comorbidities and chronic medications, disease symptoms, laboratory tests and compared the NLR and PLR between the two groups. The 177 patients admitted to the COVID-designated department in the GMC were over three decades older than the 289 COVID-19 patients admitted to the general hospital care (HC). They had substantially more comorbidities and chronic medications. All common disease symptoms were significantly more common in the HC group. Almost two thirds of the GMC patients remained asymptomatic compared to 2.1% in the HC group. Inflammatory markers, such as CRP and LDH, were significantly higher in the HC group. The NLR and PLR were both significantly higher in the GMC cohort comprised of older frailer patients with milder disease. NLR and PLR seem to be affected more by age and frailty than COVID-19 severity.

Abstract Glioma is a devastating brain tumor with a high mortality rate attributed to the glioma stem cells (GSCs) possessing high plasticity. Marker mutations in isocitrate dehydrogenase type 1 (IDH1) and tumor protein 53 (TP53) are frequent in gliomas and impact the cell fate decisions. Understanding the GSC heterogeneity within IDH1- and TP53- mutant tumors may elucidate possible treatment targets. Here, we performed single-nucleus transcriptomics of mutant and wild-type glioma samples sorted for Sox2 stem cell marker. For the first time the rare subpopulations of Sox2 + IDH1- and TP53-mutant GSCs were characterized. In general, GSCs contained the heterogeneity root subpopulation resembling active neural stem cells capable of asymmetric division to quiescent and transit amplifying cell branches. Specifically, double-mutant GSCs revealed the commitment on highly invasive oligodendrocyte- and astroglia-like progenitors. Additionally, double-mutant GSCs displayed upregulated markers of collagen synthesis, altered lipogenesis and high migration, while wild-type GSCs expressed genes related to ATP production. Wild-type GSC root population was highly heterogeneous and lacked the signature marker expression, thus glioblastoma treatment should emphasize on establishing differentiation protocol directed against residual GSCs. For the more differentiated IDH1- and TP53-mutant gliomas we suggest therapeutic targeting of migration molecules, such as CD44.

Abstract During oncogenesis, cells become unrestrictedly proliferative thereby altering the tissue homeostasis and resulting in subsequent hyperplasia. This process is paralleled by resumption of cell cycle, aberrant DNA repair and blunting the apoptotic program in response to DNA damage. In most human cancers these processes are associated with malfunctioning of tumor suppressor p53. Intriguingly, in some cases two other members of the p53 family of proteins, transcription factors p63 and p73, can compensate for loss of p53. Although both p63 and p73 can bind the same DNA sequences as p53 and their transcriptionally active isoforms are able to regulate the expression of p53-dependent genes, the strongest overlap with p53 functions was detected for p73. Surprisingly, unlike p53, the p73 is rarely lost or mutated in cancers. On the contrary, its inactive isoforms are often overexpressed in cancer. In this review, we discuss several lines of evidence that cancer cells develop various mechanisms to repress p73-mediated cell death. Moreover, p73 isoforms may promote cancer growth by enhancing an anti-oxidative response, the Warburg effect and by repressing senescence. Thus, we speculate that the role of p73 in tumorigenesis can be ambivalent and hence, requires new therapeutic strategies that would specifically repress the oncogenic functions of p73, while keeping its tumor suppressive properties intact.

Matan Elkan,1 Ayana Dvir,2 Ronit Zaidenstein,1,3 Maly Keller,1 Dana Kagansky,1 Chen Hochman,1 Ronit Koren1,3 1Department of Internal Medicine A, Shamir (Assaf Harofeh) Medical Center, Zerifin, Israel; 2Intensive Care Unit, Shamir (Assaf Harofeh) Medical Center, Zerifin, Israel; 3Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, IsraelCorrespondence: Matan ElkanDepartment of Internal Medicine A, Shamir (Assaf Harofeh) Medical Center, Zerifin, 7030000, IsraelTel +972-8-977-9242Fax + 972-8-977-9243Email matanelkan@gmail.comBackground: Many people recovering from COVID-19 suffer from long-term sequelae. The objective of this study was to assess health-related quality of life (HRQoL) in COVID-19 patients several months after discharge.Methods: We conducted a retrospective cross-sectional case–control study on COVID-19 and non-COVID-19 pneumonia patients admitted to Shamir Medical Center, Israel (03– 07/2020). In the months following discharge, patients were invited to participate in a survey and fill the RAND-36 questionnaire. Patients’ characteristics and comorbidities were extracted from electronic charts.Results: Among 66 COVID-19 participants, the median age was 58.5 (IQR 49.8– 68.3), 56.1% were female, and 36.4% were obese. The median length of stay was 7 days (IQR 4– 10). Patient-reported outcome measures were reported at a median follow-up of 9-months (IQR 6– 9). Pain, general health, vitality, and health change had the lowest scores (67.5, 60, 57.5, and 25, respectively). Matching to patients hospitalized with pneumonia due to other pathogens was performed on 42 of the COVID-19 patients. Non-COVID-19 patients were more frequently current or past smokers (50% vs 11.9%, p < 0.01) and suffered more often from chronic lung disease (38.1% vs 9.5%, p = 0.01). The score for health change was significantly lower in the COVID-19 group (25 vs 50, p < 0.01).Conclusion: Post COVID-19 patients continue to suffer from an assortment of symptoms and perceive a deterioration in their health many months after hospitalization. This emphasizes the importance of prolonged medical follow-up in this population, and the need for additional research to better understand this novel disease’s long-term effects.Keywords: COVID-19, SARS-CoV-2, long COVID, health-related quality of life, patient-reported outcome measures

Abstract Plant-derived extracellular vesicles (EVs) gain more and more attention as promising carriers of exogenous bioactive molecules to the human cells. Derived from various edible sources, these EVs are remarkably biocompatible, biodegradable and highly abundant from plants. In this work, EVs from grapefruit juice were isolated by differential centrifugation followed by characterization of their size, quantity and morphology by nanoparticle tracking analysis, dynamic light scattering, atomic force microscopy and cryo-electron microscopy (Cryo-EM). In Cryo-EM experiments, we visualized grapefruit EVs with the average size of 41 ± 13 nm, confirmed their round-shaped morphology and estimated the thickness of their lipid bilayer as 5.3 ± 0.8 nm. Further, using cell culture models, we have successfully demonstrated that native grapefruit-derived extracellular vesicles (GF-EVs) are highly efficient carriers for the delivery of the exogenous Alexa Fluor 647 labeled bovine serum albumin (BSA) and heat shock protein 70 (HSP70) into both human peripheral blood mononuclear cells and colon cancer cells. Interestingly, loading to plant EVs significantly ameliorated the uptake of exogenous proteins by human cells compared to the same proteins without EVs. Most importantly, we have confirmed the functional activity of human recombinant HSP70 in the colon cancer cell culture upon delivery by GF-EVs. Analysis of the biodistribution of GF-EVs loaded with 125I-labeled BSA in mice demonstrated a significant uptake of the grapefruit-derived extracellular vesicles by the majority of organs. The results of our study indicate that native plant EVs might be safe and effective carriers of exogenous proteins into human cells.

During cancer genesis, the extracellular matrix (ECM) in the human brain undergoes important transformations, starting to resemble embryonic brain cell milieu with a much denser structure. However, the stiffness of the tumor ECM does not preclude cancer cells from migration. The importance of the ECM role in normal brain tissue as well as in tumor homeostasis has engaged much effort in trials to implement ECM as a target and an instrument in the treatment of brain cancers. This review provides a detailed analysis of both experimental and applied approaches in combined therapy for gliomas in adults. In general, matrix materials for glioma treatment should have properties facilitating the simplest delivery into the body. Hence, to deliver an artificial implant directly into the operation cavity it should be packed into a gel form, while for bloodstream injections matrix needs to be in the form of polymer micelles, nanoparticles, etc. Furthermore, the delivered material should mimic biomechanical properties of the native tissue, support vital functions, and slow down or stop the proliferation of surrounding cells for a prolonged period. The authors propose a two-step approach aimed, on the one hand, at elimination of remaining cancer cells and on the other hand, at restoring normal brain tissue. Thereby, the first bioartificial matrix to be applied should have relatively low elastic modulus should be loaded with anticancer drugs, while the second material with a higher elastic modulus for neurite outgrowth support should contain specific factors stimulating neuroregeneration.

Esophageal cancer is an increasing concern due to poor prognosis, aggressive disease modalities, and a lack of efficient therapeutics. The two types of esophageal cancer: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are responsible for an estimated 450,000 annual deaths, with over 457,000 new patients diagnosed in 2015, making it the eighth most prevalent and the 10th most fatal cancer worldwide. As esophageal cancer prevalence continues to increase, and so does the pressing need for the development of new and effective strategies for the early diagnostics, prevention, and treatment of this cancer, as well for building the innovative research tools to understand the affected molecular mechanisms. This short review summarizes the current statistics and recent research of the problems and solutions related to the esophageal cancer, and offer a brief overview of its epidemiology, molecular alterations, and existing biomedical tools. We will discuss currently available research tools and discuss selected approaches we deem relevant to find new model systems and therapies for the future with the special focus on novel opportunities presented by the unique molecules found in algae, namely carbohydrates and lipids. Their remarkable chemical variability is connected to their striking structural and functional properties, which combined with the relative novelty of these compounds to cancer biology, warrants interest of the wide biomedical community to these molecules, especially in the esophageal cancer theory and practice.

The modulation of tumor growth and development in vitro has always been one of the key factors in the research of the malignant transformation, including gliomas, prevalent and most deadly cancers of the brain. Indeed, cellular and molecular biology research employing in vitro model cell-based systems have great potential to advance both the mechanistic understanding and the treatment of human glial tumors, as it facilitates not only the understanding of glioma biology and its regulatory mechanisms Additionally they promise to afford the screening of the putative anti-tumor agents and alternative treatment approaches in a personalized manner, i.e. by virtue of using the patient-derived tumor material for such tests. However, in order to become reliable and representative, glioma model systems need to move towards including most inherent cancer features such as local hypoxia, specific genetic aberrations, native tumor microenvironment, and the three-dimensional extracellular matrix. This review starts with a brief introduction on the general epidemiological and molecular characteristics of gliomas followed by an overview of the cell-based in vitro models currently used in glioma research. As a conclusion, we suggest approaches to move to innovative cell-based in vitro glioma models. We consider that main criteria for selecting these approaches should include the adequate resemblance to the key in vivo characteristics, robustness, cost-effectiveness and ease to use, as well as the amenability to high throughput handling to allow the standardized drug screening.

Understanding the mechanisms that regulate cancer progression is pivotal for the development of new therapies. Although p53 is mutated in half of human cancers, its family member p73 is not. At the same time, isoforms of p73 are often overexpressed in cancers and p73 can overtake many p53 functions to kill abnormal cells. According to the latest studies, while p73 represses epithelial–mesenchymal transition and metastasis, it can also promote tumour growth by modulating crosstalk between cancer and immune cells in the tumor microenvironment, M2 macrophage polarisation, Th2 T-cell differentiation, and angiogenesis. Thus, p73 likely plays a dual role as a tumor suppressor by regulating apoptosis in response to genotoxic stress or as an oncoprotein by promoting the immunosuppressive environment and immune cell differentiation.

Cellular quiescence is a reversible, non-cycling state controlled by epigenetic, transcriptional and niche-associated molecular factors. Quiescence is a condition where molecular signaling pathways maintain the poised cell-cycle state whilst enabling rapid cell cycle re-entry. To achieve therapeutic breakthroughs in oncology it is crucial to decipher these molecular mechanisms employed by the cancerous milieu to control, maintain and gear stem cells towards re-activation. Cancer stem-like cells (CSCs) have been extensively studied in most malignancies, including glioma. Here, the aberrant niche activities skew the quiescence/activation equilibrium, leading to rapid tumor relapse after surgery and/or chemotherapy. Unraveling quiescence mechanisms promises to afford prevention of (often multiple) relapses, a key problem in current glioma treatment. This review article covers the current knowledge regarding normal and aberrant cellular quiescence control whilst also exploring how different molecular mechanisms and properties of the neighboring cells can influence the molecular processes behind glioma stem cell quiescence.

According to the World Health Organization, the population of over 60 will double in the next 30 years in the developed countries, which will enforce a further raise of the retirement age and increase the burden on the healthcare system. Therefore, there is an acute issue of maintaining health and prolonging active working longevity, as well as implementation of early monitoring and prevention of premature aging and age-related disorders to avoid early disability. Traditional indicators of biological age are not always informative and often require extensive and expensive analysis. The study of blood factors is a simple and easily accessible way to assess individual health and supplement the traditional indicators of a person’s biological age with new objective criteria. With age, the processes of growth and development, tissue regeneration and repair decline; they are gradually replaced by enhanced catabolism, inflammatory cell activity, and insulin resistance. The number of senescent cells supporting the inflammatory loop rises; cellular clearance by autophagy and mitophagy slows down, resulting in mitochondrial and cellular damage and dysfunction. Monitoring of circulated blood factors not only reflects these processes, but also allows suggesting medical intervention to prevent or decelerate the development of age-related diseases. We review the age-related blood factors discussed in recent publications, as well as approaches to slowing aging for healthy and active longevity.

Epithelial organs are the first barrier against microorganisms and genotoxic stress, in which the p53 family members p63 and p73 have both overlapping and distinct functions. Intriguingly, p73 displays a very specific localization to basal epithelial cells in human tissues, while p63 is expressed in both basal and differentiated cells. Here, we analyse systematically the literature describing p63 and p73 protein–protein interactions to reveal distinct functions underlying the aforementioned distribution. We have found that p73 and p63 cooperate in the genome stability surveillance in proliferating cells; p73 specific interactors contribute to the transcriptional repression, anaphase promoting complex and spindle assembly checkpoint, whereas p63 specific interactors play roles in the regulation of mRNA processing and splicing in both proliferating and differentiated cells. Our analysis reveals the diversification of the RNA and DNA specific functions within the p53 family.

Aims: Endotoxemia commonly occurs in severe and fatal COVID‐19, suggesting that concomitant bacterial stimuli may amplify the innate immune response induced by SARS‐CoV‐2. We previously demonstrated that the endogenous glucagon like peptide 1 (GLP‐1) system in conjunction with increased procalcitonin (PCT) is hyperactivated in patients with severe Gram‐negative sepsis and modulated by type 2 diabetes (T2D). We aimed to determine the association of COVID‐19 severity with endogenous GLP‐1 activation upregulated by increased specific pro‐inflammatory innate immune response in patients with and without T2D. Materials and Methods: Plasma levels of total GLP‐1, IL‐6, and PCT were estimated on admission and during hospitalisation in 61 patients (17 with T2D) with non‐severe and severe COVID‐19. Results: COVID‐19 patients demonstrated ten‐fold increase of IL‐6 levels regardless of disease severity. Increased admission GLP‐1 levels (p = 0.03) accompanied by two‐fold increased PCT were found in severe as compared with non‐severe patients. Moreover, GLP‐1 and PCT levels were significantly increased in non‐survived as compared with survived patients at admission (p = 0.01 and p = 0.001, respectively) and at 5 to 6 days of hospitalisation (p = 0.05). Both non‐diabetic and T2D patients demonstrated a positive correlation between GLP‐1 and PCT response (r = 0.33, p = 0.03, and r = 0.54, p = 0.03, respectively), but the intensity of this joint pro‐inflammatory/GLP‐1 response was modulated by T2D. In addition, hypoxaemia down‐regulated GLP‐1 response only in T2D patients with bilateral lung damage. Conclusions: The persistent joint increase of endogenous GLP‐1 and PCT in severe and fatal COVID‐19 suggests a role of concomitant bacterial infection in disease exacerbation. Early elevation of endogenous GLP‐1 may serve as a new biomarker of COVID‐19 severity and fatal outcome. [ABSTRACT FROM AUTHOR]

The effect of over- and undertreatment of hypothyroidism on hospitalization outcomes of patients with acute decompensated heart failure (HF) has not been evaluated yet. We conducted retrospective cohort analyses of outcomes among 231 consecutive patients with treated hypothyroidism who were admitted to internal medicine departments of Shamir Medical Center with HF (2011–2019). Patients were divided into three groups according to their thyroid-stimulating hormone (TSH) levels: well treated (TSH: 0.4–4 mIU/L), overtreated (TSH: <0.4 mIU/L), and undertreated (TSH: >4 mIU/L). The main outcomes were mortality and recurrent hospitalization within 3 months. Among 231 patients, 106 were euthyroid, 14 were overtreated, and 111 undertreated. Patients' mean age was 79.8 ± 9.4 years. In-hospital mortality occurred in 4.7% in euthyroid patients, 14.3% in the overtreated group, and 10.7% in the undertreated group (p = 0.183). Differences in 30-day (p = 0.287) and 90-day (p = 0.2) mortality or recurrent hospitalization (p = 0.438) were not significantly different as well. However, in patients who were markedly undertreated and overtreated (TSH: >10 mIU/L or below 0.4 mIU/L) compared with 0.4–10 mIU/L, a significant increase in 90-day mortality was observed (33.3% vs 15.1% p = 0.016). Treatment status was independently associated with 90-day mortality after controlling for confounders with an adjusted odds ratio of 3.55 (95% confidence interval: 1.39–9.06). Although mild under- or overtreatment of hypothyroidism does not have a significant detrimental effect on hospitalization outcomes of patients with acute decompensated HF, markedly under- and overtreatment are independently associated with rehospitalizations and 90-day mortality. Larger cohorts are needed to establish the relationship between treatment targets and hospitalization outcomes of patients at risk for HF hospitalization. [ABSTRACT FROM AUTHOR]

Epigenetic silencing is the reversible inactivation of a gene transcription which occurs as a result of changes in the structure of the chromatin that can be successfully inherited from parent to daughter cells. It involves non-genetic mutations within the genome, as well as post-transcriptional and post-translational mechanisms. Existence of these mechanisms at various levels warrants their role in development and disease and thus it is crucial to study different factors and mechanisms of silencing. The aim of our study was to establish a method for rapid screening for the loss of epigenetic silencing in mammalian cells, to identify factor(s) involved in epigenetic silencing, and to get insights into their mechanism of action. For this purpose, we used RNAi screening approach using shRNAs that targeted our genes of interest. We employed a modified mouse cell line which contained a GFP transgene under the control of CMV promoter which has been silenced by epigenetic modifications. Our screening identified several proteins as epigenetic silencing regulators including Kat5/Tip60, an acetyltransferase of MYST family of proteins. To characterize its function, we performed preliminary experiments using microscopy and Western blot analysis of histone marks. We observed changes in H4 acetylation levels in Kat5/Tip60 knockdown cells. Our study thus serves as a pilot for a genome-wide silencing screening using mammalian cells, and provides preliminary results suggesting that Kat5 can be considered as a silencing factor, which, we propose, could function by maintaining H4 acetylation patterns.