Corneal Neurotization: Essentials for The Facial Paralysis Surgeon.

Deficits in corneal innervation lead to neurotrophic keratopathy (NK). NK is frequently associated with facial palsy, and corneal damage can be accelerated by facial palsy deficits. Corneal nerves are important regulators of limbal stem cells, which play a critical role in epithelial maintenance and healing. Nonsurgical treatments of NK have undergone recent innovation, and growth factors implicated in corneal epithelial renewal are a promising therapeutic avenue. However, surgical intervention with corneal neurotization (CN) remains the only definitive treatment of NK. CN involves the transfer of unaffected sensory donor nerve branches to the affected cornea, and a variety of donor nerves and approaches have been described. CN can be performed in a direct or indirect manner; employ the supraorbital, supratrochlear, infraorbital, or great auricular nerves; and utilize autograft, allograft, or nerve transfer alone. Unfortunately, comparative studies of these factors are limited due to the procedure's novelty and varied recovery timelines after CN. Regardless of the chosen approach, CN has been shown to be a safe and effective procedure to restore corneal sensation and improve visual acuity in patients with NK.

Coordinated removal of repressive epigenetic modifications during induced reversal of cell identity.

Epigenetic modifications operate in concert to maintain cell identity, yet how these interconnected networks suppress alternative cell fates remains unknown. Here, we uncover a link between the removal of repressive histone H3K9 methylation and DNA methylation during the reprogramming of somatic cells to pluripotency. The H3K9me2 demethylase, Kdm3b, transcriptionally controls DNA hydroxymethylase Tet1 expression. Unexpectedly, in the absence of Kdm3b, loci that must be DNA demethylated are trapped in an intermediate hydroxymethylated (5hmC) state and do not resolve to unmethylated cytosine. Ectopic 5hmC trapping precludes the chromatin association of master pluripotency factor, POU5F1, and pluripotent gene activation. Increased Tet1 expression is important for the later intermediates of the reprogramming process. Taken together, coordinated removal of distinct chromatin modifications appears to be an important mechanism for altering cell identity.

Sarcopenia and body fat change as risk factors for radiologic incisional hernia following robotic nephrectomy.

OBJECTIVE: To assess the effect of body muscle and fat metrics on the development of radiologic incisional hernia (IH) following robotic nephrectomy. MATERIALS AND METHODS: We retrospectively reviewed the records of patients who underwent robotic nephrectomy for kidney tumors between 2011 and 2017. All pre- and postoperative CTs were re-reviewed by experienced radiologists for detection of radiologic IH and calculation of the following metrics using Synapse 3D software: cross-sectional psoas muscle mass at the level of L3 and L4 as well as subcutaneous and visceral fat areas. Sarcopenia was defined as psoas muscle index below the lowest quartile. Cox proportional hazard model was constructed to examine the association between muscle and fat metrics and the risk of developing radiologic IH. RESULTS: A total of 236 patients with a median (IQR) age of 64 (54-70) years were included in this study. In a median (IQR) follow-up of 23 (14-38) months, 62 (26%) patients developed radiologic IH. On Cox proportional hazard model, we were unable to detect an association between sarcopenia and risk of IH development. In terms of subcutaneous fat change from pre-op, both lower and higher values were associated with IH development (HR (95% CI) 2.1 (1.2-3.4), p = 0.01 and 2.4 (1.4-4.1), p < 0.01 for < Q1 and ≥ Q3, respectively). Similar trend was found for visceral fat area changes from pre-op with a HR of 2.8 for < Q1 and 1.8 for ≥ Q3. CONCLUSION: Both excessive body fat gain and loss are associated with development of radiologic IH in patients undergoing robotic nephrectomy.

The impact of cage positioning on lumbar lordosis and disc space restoration following minimally invasive lateral lumbar interbody fusion.

OBJECTIVE: The objective of this study was to evaluate patient and surgical factors that predict increased overall lumbar lordosis (LL) and segmental lordosis correction following a minimally invasive lateral lumbar interbody fusion (LLIF) procedure. METHODS: A retrospective review was conducted of all patients who underwent one- or two-level LLIF. Preoperative, initial postoperative, and 6-month postoperative measurements of LL, segmental lordosis, anterior disc height, and posterior disc height were collected from standing lateral radiographs for each patient. Cage placement was measured utilizing the center point ratio (CPR) on immediate postoperative radiographs. Spearman correlations were used to assess associations between cage lordosis and radiographic parameters. Multivariate linear regression was performed to assess independent predictors of outcomes. RESULTS: A total of 106 levels in 78 unique patients were included. Most procedures involved fusion of one level (n = 50, 64.1%), most commonly L3-4 (46.2%). Despite no differences in baseline segmental lordosis, patients with anteriorly or centrally placed cages experienced the greatest segmental lordosis correction immediately (mean anterior 4.81° and central 4.46° vs posterior 2.47°, p = 0.0315) and at 6 months postoperatively, and patients with anteriorly placed cages had greater overall lordosis correction postoperatively (mean 6.30°, p = 0.0338). At the 6-month follow-up, patients with anteriorly placed cages experienced the greatest increase in anterior disc height (mean anterior 6.24 mm vs posterior 3.69 mm, p = 0.0122). Cages placed more posteriorly increased the change in posterior disc height postoperatively (mean posterior 4.91 mm vs anterior 1.80 mm, p = 0.0001) and at 6 months (mean posterior 4.18 mm vs anterior 2.06 mm, p = 0.0255). There were no correlations between cage lordotic angle and outcomes. On multivariate regression, anterior cage placement predicted greater 6-month improvement in segmental lordosis, while posterior placement predicted greater 6-month improvement in posterior disc height. Percutaneous screw placement, cage lordotic angle, and cage height did not independently predict any radiographic outcomes. CONCLUSIONS: LLIF procedures reliably improve LL and increase intervertebral disc space. Anterior cage placement improves the lordosis angle greater than posterior placement, which better corrects sagittal alignment, but there is still a significant improvement in lordosis even with a posteriorly placed cage. Posterior cage placement provides greater restoration in posterior disc space height, maximizing indirect decompression, but even the anteriorly placed cages provided indirect decompression. Cage parameters including cage height, lordosis angle, and material do not impact radiographic improvement.

Understanding trends in loneliness during the COVID-19 pandemic in The Netherlands: the moderating role of gender, age, and living arrangement.

Objectives: Evidence suggests that the COVID-19 pandemic and the preventive lockdown measures increased loneliness levels. However, most studies are cross-sectional or rely on a pre-post (pandemic) design. This study relies on multiple observations to analyze the impact of the lockdown on loneliness levels in the Netherlands, and test whether it differed by gender, age, and living arrangement.Methods: Longitudinal data from the Covid-Questionnaire within the Lifelines Cohort Study from the northern Netherlands was used. Data was gathered between March 2020 and July 2021 with a total of 21 waves and 769,526 observations nested in 74,844 individuals. The outcome was a multi-dimensional Loneliness Index. The association between the lockdown period and loneliness levels was estimated using fixed-effects linear regression. Moderation effects were tested by means of two-way interactions.Results: Loneliness levels increased during stricter lockdown periods, and decreased when preventive measures were relaxed. Women and young adults experienced stronger fluctuations in their loneliness levels, whereas living arrangement did not play a notable moderating role.Conclusion: This study calls for special attention to be paid to the public issue of loneliness during periods of lockdown. Women and young adults appear as particularly vulnerable groups during the Covid-19 pandemic.

Effects of Essential Oils and Fragrant Compounds on Appetite: A Systematic Review.

Appetite dysregulation is one of the factors contributing to anorexia, bulimia nervosa, obesity, and diabetes. Essential oils or fragrant compounds have been proven to regulate food intake and energy expenditure; hence, this study aimed to summarize their effects on appetite and the underlying mechanisms. The PubMed and Web of Science databases were searched until July 2022. Only two of the 41 studies were performed clinically, and the remaining 39 used animal models. Oral administration was the most common route, and a dosage range of 100-2000 mg/kg for mice or 2-32 mg/kg for rats was applied, with a duration of 12 days to 4 weeks, followed by inhalation (10-6-10-3 mg/cage or 10-9-10-2 mg/cm3 within 1 h). Approximately 11 essential oil samples and 22 fragrant compounds were found to increase appetite, while 12 essential oils and seven compounds decreased appetite. These fragrant components can exert appetite-regulating effects via leptin resistance, the activity of sympathetic/parasympathetic nerves, or the mRNA expression of neuropeptide Y (NPY)/agouti-related protein (AgRP), cocaine- and amphetamine-regulated transcript (CART)/proopiomelanocortin (POMC) in the hypothalamus. Fragrance memory and cognitive processes may also play roles in appetite regulation. The findings of this study accentuate the potential of essential oils and fragrant compounds to regulate appetite and eating disorders.

Community-wide Screening for Tuberculosis in a High-Prevalence Setting.

BACKGROUND: The World Health Organization has set ambitious targets for the global elimination of tuberculosis. However, these targets will not be achieved at the current rate of progress. METHODS: We performed a cluster-randomized, controlled trial in Ca Mau Province, Vietnam, to evaluate the effectiveness of active community-wide screening, as compared with standard passive case detection alone, for reducing the prevalence of tuberculosis. Persons 15 years of age or older who resided in 60 intervention clusters (subcommunes) were screened for pulmonary tuberculosis, regardless of symptoms, annually for 3 years, beginning in 2014, by means of rapid nucleic acid amplification testing of spontaneously expectorated sputum samples. Active screening was not performed in the 60 control clusters in the first 3 years. The primary outcome, measured in the fourth year, was the prevalence of microbiologically confirmed pulmonary tuberculosis among persons 15 years of age or older. The secondary outcome was the prevalence of tuberculosis infection, as assessed by an interferon gamma release assay in the fourth year, among children born in 2012. RESULTS: In the fourth-year prevalence survey, we tested 42,150 participants in the intervention group and 41,680 participants in the control group. A total of 53 participants in the intervention group (126 per 100,000 population) and 94 participants in the control group (226 per 100,000) had pulmonary tuberculosis, as confirmed by a positive nucleic acid amplification test for Mycobacterium tuberculosis (prevalence ratio, 0.56; 95% confidence interval [CI], 0.40 to 0.78; P<0.001). The prevalence of tuberculosis infection in children born in 2012 was 3.3% in the intervention group and 2.6% in the control group (prevalence ratio, 1.29; 95% CI, 0.70 to 2.36; P = 0.42). CONCLUSIONS: Three years of community-wide screening in persons 15 years of age or older who resided in Ca Mau Province, Vietnam, resulted in a lower prevalence of pulmonary tuberculosis in the fourth year than standard passive case detection alone. (Funded by the Australian National Health and Medical Research Council; ACT3 Australian New Zealand Clinical Trials Registry number, ACTRN12614000372684.).

Prevalence, Anatomic Distribution, and Correlates of Chlamydia trachomatis and Neisseria gonorrhoeae Infections Among a Cohort of Men Who Have Sex With Men in Hanoi, Vietnam.

BACKGROUND: Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) disproportionately affect men who have sex with men (MSM). Data on the prevalence, anatomical distribution, and correlates of NG and CT infections among MSM in Vietnam are limited. METHODS: Between July 2017 and April 2019, MSM 16 years or older without HIV were enrolled into an observational cohort study. Baseline data, including sociodemographics, sexual behavior, and HIV status, were collected. Testing for NG and CT were performed on urine, rectal, and pharyngeal specimens. Multivariate logistic regression models identified factors associated with NG and CT infections at baseline. RESULTS: In total, 1489 participants underwent NG/CT testing. The median age was 22 years (interquartile range, 20-26 years). There were 424 (28.5%) NG or CT infections: 322 (21.6%) with CT and 173 (11.6%) with NG. Rectal infections were most common for CT (73.9%), whereas pharyngeal infections were most common for NG (70.5%). Independent risk factors for CT or NG infection included ≥2 sex partners in the prior month (adjusted odds ratio [aOR], 2.04; 95% confidence interval [CI], 1.44-2.91), condomless anal sex (aOR, 1.44; 95% CI, 1.12-1.86), and meeting sex partners online (aOR, 1.35; 95% CI, 1.03-1.76). Recent genitourinary or rectal symptoms were not associated with infections. CONCLUSIONS: The overall and extragenital prevalences of NG and CT infections were high within this sample of young MSM without HIV in Hanoi. Testing limited to urethral specimens would have missed nearly three-quarters of CT and NG infections, supporting the need for routine testing at multiple anatomic sites.

A novel non-invasive index of oxygenation and prediction of outcomes for patients on high-flow nasal cannula: a pilot study.

Predicting success of a therapy in acute respiratory failure is clinically important. The FOx index (high-flow rate × FiO2 )/SpO2 was retrospectively applied to 70 patients who required high-flow nasal prongs for hypoxaemic and hypercapnic respiratory failure. The FOx index could predict between success and failure of high-flow nasal prongs at 6 hours, using non-invasive markers. This adds to the clinician's toolbox in managing respiratory failure and represents important proof of concept for a prospective study.

FedSGDCOVID: Federated SGD COVID-19 Detection under Local Differential Privacy Using Chest X-ray Images and Symptom Information.

Coronavirus (COVID-19) has created an unprecedented global crisis because of its detrimental effect on the global economy and health. COVID-19 cases have been rapidly increasing, with no sign of stopping. As a result, test kits and accurate detection models are in short supply. Early identification of COVID-19 patients will help decrease the infection rate. Thus, developing an automatic algorithm that enables the early detection of COVID-19 is essential. Moreover, patient data are sensitive, and they must be protected to prevent malicious attackers from revealing information through model updates and reconstruction. In this study, we presented a higher privacy-preserving federated learning system for COVID-19 detection without sharing data among data owners. First, we constructed a federated learning system using chest X-ray images and symptom information. The purpose is to develop a decentralized model across multiple hospitals without sharing data. We found that adding the spatial pyramid pooling to a 2D convolutional neural network improves the accuracy of chest X-ray images. Second, we explored that the accuracy of federated learning for COVID-19 identification reduces significantly for non-independent and identically distributed (Non-IID) data. We then proposed a strategy to improve the model's accuracy on Non-IID data by increasing the total number of clients, parallelism (client-fraction), and computation per client. Finally, for our federated learning model, we applied a differential privacy stochastic gradient descent (DP-SGD) to improve the privacy of patient data. We also proposed a strategy to maintain the robustness of federated learning to ensure the security and accuracy of the model.

Anxiolytic-like Effect of Inhaled Cinnamon Essential Oil and Its Main Component Cinnamaldehyde in Animal Models.

Aromatherapy is one of the most common safer alternative treatments for psychiatric disorders with fewer side effects than conventional drugs. Here, we investigated the effects of cinnamon essential oil (CIEO) inhalation on mouse behaviors by performing different behavioral tests. CIEO inhalation showed anxiolytic effects in the elevated plus maze test, as inferred from increased time spent in open arms and decreased time spent in closed arms. Moreover, the CIEO treatment enhanced social behavior by increasing the total contact number, time spent in the center, distance traveled in the center, and total distance in the social interaction test. However, CIEO inhalation did not have any effect on performance in the open field test, tail suspension test, forced swimming test, and Y maze tests. The microarray analysis indicated that the CIEO treatment downregulated 17 genes and upregulated 15 genes in the hippocampus. Among them, Dcc, Egr2, and Fos are the most crucial genes that are involved in anxiety-related biological processes and pathways, including the regulation of neuronal death and neuroinflammation. Gas chromatography/mass spectrometry analysis revealed that cinnamaldehyde is the main component of CIEO. Cinnamaldehyde recovered MK-801-induced anxiety-related changes in the electroencephalogram power spectrum in zebrafish. Taken together, our findings suggest that CIEO and its main component cinnamaldehyde have an anxiolytic effect through the regulation of the expression of genes related to neuroinflammatory response and neuronal death.

A cytoskeletal protein complex is essential for division of intracellular amastigotes of Leishmania mexicana.

Previous studies in Leishmania mexicana have identified the cytoskeletal protein KHARON as being important for both flagellar trafficking of the glucose transporter GT1 and for successful cytokinesis and survival of infectious amastigote forms inside mammalian macrophages. KHARON is located in three distinct regions of the cytoskeleton: the base of the flagellum, the subpellicular microtubules, and the mitotic spindle. To deconvolve the different functions for KHARON, we have identified two partner proteins, KHAP1 and KHAP2, which associate with KHARON. KHAP1 is located only in the subpellicular microtubules, whereas KHAP2 is located at the subpellicular microtubules and the base of the flagellum. Both KHAP1 and KHAP2 null mutants are unable to execute cytokinesis but are able to traffic GT1 to the flagellum. These results confirm that KHARON assembles into distinct functional complexes and that the subpellicular complex is essential for cytokinesis and viability of disease-causing amastigotes but not for flagellar membrane trafficking.

The prevalence of perceived stigma and self-blame and their associations with depression, emotional well-being and social well-being among advanced cancer patients: evidence from the APPROACH cross-sectional study in Vietnam.

BACKGROUND: There is very limited evidence on the existence of cancer-related perceived stigma and self-blame among patients with advanced cancer in Asia, and how they are associated with psychosocial outcomes. This study aimed to address the gap in the current literature by (1) assessing perceived stigma, behavioural self-blame and characterological self-blame among Vietnamese patients with advanced cancer, and (2) investigating the associations of perceived stigma and self-blame (behavioural and characterological) with depression, emotional well-being and social well-being. METHODS: This cross-sectional study involved 200 Vietnamese patients with stage IV solid cancer. Depression was measured using the Center for Epidemiologic Studies Depression (CES-D) Scale. Emotional well-being and social well-being were measured with the relevant domains of the Functional Assessment of Cancer Therapy-General (FACT-G) scale. Perceived stigma was assessed using the sense of stigma subscale of Kissane's Shame and Stigma Scale. Behavioural self-blame and characterological self-blame were measured by the patients' answers to the questions on whether their cancer was due to patient's behaviour or character. Multivariable linear regressions were used to investigate the associations while controlling for patient characteristics. RESULTS: Approximately three-fourths (79.0%, n = 158) of the participants reported perceived stigma with an average score of 20.5 ± 18.0 (out of 100). More than half of the participants reported behavioural self-blame (56.3%, n = 112) or characterological self-blame (62.3%, n = 124). Higher perceived stigma was associated with lower emotional well-being (ß = -0.0; p = 0.024). Behavioural self-blame was not significantly associated with depressive symptoms, emotional well-being or social well-being. Patients who reported characterological self-blame reported greater depressive symptoms (ß = 3.0; p = 0.020) and lower emotional well-being (ß = -1.6; p = 0.038). CONCLUSION: Perceived stigma and self-blame were common amongst Vietnamese advanced cancer patients. Perceived stigma was associated with lower emotional well-being while characterological self-blame were associated with greater depressive symptoms and lower emotional well-being. Interventions should address perceived stigma and self-blame among this population.

Adaptive local false discovery rate procedures for highly spiky data and their application RNA sequencing data of yeast SET4 deletion mutants.

Chromatin dynamics are central to the regulation of gene expression and genome stability. In order to improve understanding of the factors regulating chromatin dynamics, the genes encoding these factors are deleted and the differential gene expression profiles are determined using approaches such as RNA sequencing. Here, we analyzed a gene expression dataset aimed at uncovering the function of the relatively uncharacterized chromatin regulator, Set4, in the model system Saccharomyces cerevisiae (budding yeast). The main theme of this paper focuses on identifying the highly differentially expressed genes in cells deleted for Set4 (referred to as Set4 Δ mutant dataset) compared to the wild-type yeast cells. The Set4 Δ mutant data produce a spiky distribution on the log-fold changes of their expressions, and it is reasonably assumed that genes which are not highly differentially expressed come from a mixture of two normal distributions. We propose an adaptive local false discovery rate (FDR) procedure, which estimates the null distribution of the log-fold changes empirically. We numerically show that, unlike existing approaches, our proposed method controls FDR at the aimed level (0.05) and also has competitive power in finding differentially expressed genes. Finally, we apply our procedure to analyzing the Set4 Δ mutant dataset.

The role of α-ketoglutarate-dependent proteins in pluripotency acquisition and maintenance.

α-Ketoglutarate is an important metabolic intermediate that acts as a cofactor for several chromatin-modifying enzymes, including histone demethylases and the Tet family of enzymes that are involved in DNA demethylation. In this review, we focus on the function and genomic localization of these α-ketoglutarate-dependent enzymes in the maintenance of pluripotency during cellular reprogramming to induced pluripotent stem cells and in disruption of pluripotency during in vitro differentiation. The enzymatic function of many of these α-ketoglutarate-dependent proteins is required for pluripotency acquisition and maintenance. A better understanding of their specific function will be essential in furthering our knowledge of pluripotency.

Vascularized Lymph Node Transfer: A Primer for the Radiologist.

Lymphedema, the accumulation of lymphatic fluid in the tissues, is a chronic disease and a major cause of long-term morbidity and disability. Lymphedema is usually a secondary condition, often caused by prior oncologic therapy, such as surgery for cancers, radiation therapy, and chemotherapy. Treatment for lymphedema has traditionally been conservative and limited, but new surgical and microsurgical procedures have arisen in recent years. Vascularized lymph node transfer (VLNT) is one of the most promising new microsurgeries. VLNT involves the transfer of functional lymph nodes (LNs) from a healthy donor site to an area of the body with damaged or diseased lymphatic drainage. The goal of the transplant is to restore physiologic LN drainage and improve lymphedema. Donor LNs are commonly found in the groin, axilla, neck, omentum, or submental region. Imaging can be used for preoperative planning to identify donor sites with the richest number of LNs. This can help identify those patients who may be candidates for VLNT and can help identify the best anatomic site for surgical harvest in those candidates. Imaging can be performed with US, CT, or MRI. VLNT preoperative imaging often requires acquisition techniques and reconstruction parameters that differ from those used in routine diagnostic imaging. Furthermore, to properly identify target LNs, the radiologist must be aware of surgical anatomic landmarks. Online supplemental material is available for this article. ©RSNA, 2020.

Set4 is a chromatin-associated protein, promotes survival during oxidative stress, and regulates stress response genes in yeast.

The Set4 protein in the yeast Saccharomyces cerevisiae contains both a PHD finger and a SET domain, a common signature of chromatin-associated proteins, and shares sequence homology with the yeast protein Set3, the fly protein UpSET, and the human protein mixed-lineage leukemia 5 (MLL5). However, the biological role for Set4 and its potential function in chromatin regulation has not been well defined. Here, we analyzed yeast cell phenotypes associated with loss of Set4 or its overexpression, which revealed that Set4 protects against oxidative stress induced by hydrogen peroxide. Gene expression analysis indicated that Set4 promotes the activation of stress response genes in the presence of oxidative insults. Using ChIP analysis and other biochemical assays, we also found that Set4 interacts with chromatin and directly localizes to stress response genes upon oxidative stress. However, recombinant Set4 did not show detectable methyltransferase activity on histones. Our findings also suggest that Set4 abundance in the cell is balanced under normal and stress conditions to promote survival. Overall, these results suggest a model in which Set4 is a stress-responsive, chromatin-associated protein that activates gene expression programs required for cellular protection against oxidative stress. This work advances our understanding of mechanisms that protect cells during oxidative stress and further defines the role of the Set3-Set4 subfamily of SET domain-containing proteins in controlling gene expression in response to adverse environmental conditions.

Triangular Regulation of Cucurbit[8]uril 1:1 Complexes.

Triangular shapes have inspired scientists over time and are common in nature, such as the flower petals of oxalis triangularis, the triangular faces of tetrahedrite crystals, and the icosahedron faces of virus capsids. Supramolecular chemistry has enabled the construction of triangular assemblies, many of which possess functional features. Among these structures, cucurbiturils have been used to build supramolecular triangles, and we recently reported paramagnetic cucurbit[8]uril (CB[8]) triangles, but the reasons for their formation remain unclear. Several parameters have now been identified to explain their formation. At first sight, the radical nature of the guest was of prime importance in obtaining the triangles, and we focused on extending this concept to biradicals to get supramolecular hexaradicals. Two sodium ions were systematically observed by ESI-MS in trimer structures, and the presence of Na+ triggered or strengthened the triangulation of CB[8]/guest 1:1 complexes in solution. X-ray crystallography and molecular modeling have allowed the proposal of two plausible sites of residence for the two sodium cations. We then found that a diamagnetic guest with an H-bond acceptor function is equally good at forming CB[8] triangles. Hence, a guest molecule containing a ketone function has been precisely triangulated thanks to CB[8] and sodium cations as determined by DOSY-NMR and DLS. A binding constant for the triangulation of 1:1 to 3:3 complexes is proposed. This concept has finally been extended to the triangulation of ditopic guests toward network formation by the reticulation of CB[8] triangles using dinitroxide biradicals.

SET domains and stress: uncovering new functions for yeast Set4.

Chromatin dynamics are central to the regulation of gene expression and genome stability, particularly in the presence of environmental signals or stresses that prompt rapid reprogramming of the genome to promote survival or differentiation. While numerous chromatin regulators have been implicated in modulating cellular responses to stress, gaps in our mechanistic understanding of chromatin-based changes during stress suggest that additional proteins are likely critical to these responses and the molecular details underlying their activities are unclear in many cases. We recently identified a role for the relatively uncharacterized SET domain protein Set4 in promoting cell survival during oxidative stress in Saccharomyces cerevisiae. Set4 is a member of the Set3 subfamily of SET domain proteins which are defined by the presence of a PHD finger and divergent SET domain sequences. Here, we integrate our new observations on the function of Set4 with known roles for other related family members, including yeast Set3, fly UpSET and mammalian proteins MLL5 and SETD5. We discuss outstanding questions regarding the molecular mechanisms by which these proteins control gene expression and their potential contributions to cellular responses to environmental stress.