Exposure to Valsartan Products Containing Nitrosamine Impurities in the United States, Canada, and Denmark.

BACKGROUND: Following the mass recall of valsartan products with nitrosamine impurities in July 2018, the number of patients exposed to these products, the duration of exposure, and the potential for cancer remains unknown. Therefore, we assessed the extent and duration of use of valsartan products with a nitrosamine impurity in the United States, Canada, and Denmark. METHODS: We conducted a retrospective cohort study using administrative healthcare data from the US FDA Sentinel System, four Canadian provinces that contribute to the Canadian Network for Observational Drug Effect Studies (CNODES), and the Danish National Prescription Registry. Patients, 18 years and older between May 2012 and December 2020 with a valsartan dispensing were identified in each database. Patients were followed from the date of valsartan dispensing until discontinuation. We defined four valsartan exposure categories based on nitrosamine impurity status; recalled generic products with confirmed NDMA/NDEA levels (recalled-tested); recalled generic products that were not tested (recalled); non-recalled generic and non-recalled branded products. In Denmark, the recalled-tested category was not included due to absence of testing data. The proportion and duration of use of valsartan episodes stratified by nitrosamine-impurity status was calculated. RESULTS: We identified 3.3 and 2.8 million (United States) and 51.3 and 229 thousand (Canada) recalled-tested and recalled valsartan exposures. In Denmark, where valsartan exposure was generally low, there were 10 747 recalled exposures. Immediately after the recall notices were issued, there was increased rates of switching to a non-valsartan ARB. The mean duration of use of the recalled-tested products was 167 (±223.1) and 146 (±255.8) days in the United States and Canada respectively. For the recalled products, mean cumulative duration of use was 178 (±249.6), 269 (±397.3) and 166 (±251.0) days in the United States, Canada, and Denmark, respectively. CONCLUSION: In this cohort study, despite widespread use of recalled generic valsartan between 2012 and 2018, the duration of use was relatively short and probably did not pose an elevated risk of nitrosamine-induced cancer. However, since products with nitrosamine impurity could have been on the market over a 6-year period, patients exposed to these products for longer durations could have a potentially different risk of cancer.

Quad-dimensional acculturation, cultural integration, and life satisfaction of South Sudanese refugee young adults in the United States: A quasilongitudinal qualitative study.

OBJECTIVE: This study aims to describe acculturation among South Sudanese refugees (SSRes) as young adults in the U.S. based on a tridimensional (3D) acculturation framework. METHOD: Aligning with a community-based participatory research (CBPR) approach, the present study was designed to investigate in-depth individual experiences of SSRes in two phases, conducting 19 interviews in 2007 and 11 interviews in 2014-2015. The data analysis employed a modified grounded theory approach. RESULTS: A grounded theory emerged indicating that, over time, SSRes experienced quad-dimensional acculturation that included South Sudanese, mainstream American, African American, and African cultures and orientations. Although bidimensional acculturation was prominent in Phase 1, quad-dimensional acculturation emerged and was salient in Phase 2. Furthermore, participants who demonstrated an integrated perspective toward their acculturation tended to report higher life satisfaction scores than those who expressed conflicted perspectives. CONCLUSIONS: The findings have theoretical and practical implications for African refugees' adjustment and psychological well-being. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Postextraction ridge preservation by using dense PTFE membranes: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: The use of dense polytetrafluoroethylene (dPTFE) membranes in alveolar ridge preservation may help reduce the risk of bacterial contamination and infection, maintaining the soft-tissue anatomy. However, systematic reviews on their efficacy in postextraction sites are lacking. PURPOSE: The purpose of this systematic review and meta-analysis was to assess the efficacy of alveolar ridge preservation with dPTFE membranes when used alone or in combination with bone grafting materials in postextraction sites. MATERIAL AND METHODS: An electronic search up to February 2021 was conducted by using PubMed, Embase, and the Cochrane library to detect studies using dPTFE membranes in postextraction sites. An additional manual search was performed in relevant journals. Clinical and radiographic dimensional changes of the alveolar ridge, histomorphometric, microcomputed tomography, implant-related findings, and rate of complications were recorded. One-dimensional meta-analysis was performed to calculate the overall means and 95% confidence intervals (α=.05). RESULTS: A total of 23 studies, 14 randomized controlled trials, 4 retrospective cohort studies, 3 case series, and 2 prospective nonrandomized clinical trials, met the inclusion criteria. Five studies were included in the quantitative analysis. The meta-analysis revealed that the use of dPTFE membranes resulted in a statistically significant (P=.042) increase in clinical keratinized tissue of 3.49 mm (95% confidence interval [CI]: 0.16, 6.83) when compared with extraction alone. Metaregression showed that the difference of 1.10 mm (95% CI: -0.14, 2.35) in the radiographic horizontal measurements was not significant (P=.082), but the difference of 1.06 mm (95% CI: 0.51, 1.62) in the radiographic vertical dimensional change between dPTFE membranes+allograft and extraction alone was statistically significant (P<.001). CONCLUSIONS: The use of dPTFE membranes was better than extraction alone in terms of keratinized tissue width and radiographic vertical bone loss.

Susceptibility of Rat Steatotic Liver to Ischemia-Reperfusion Is Treatable With Liver-Selective Matrix Metalloproteinase Inhibition.

BACKGROUND AND AIMS: This study examined whether enhanced susceptibility of steatotic liver to ischemia-reperfusion (I/R) injury is due to impaired recruitment of bone marrow (BM) progenitors of liver sinusoidal endothelial cells (LSECs, also called sinusoidal endothelial cell progenitor cells [sprocs]) with diminished repair of injured LSECs and whether restoring signaling to recruit BM sprocs reduces I/R injury. APPROACH AND RESULTS: Hepatic vessels were clamped for 1 hour in rats fed a high-fat, high-fructose (HFHF) diet for 5, 10, or 15 weeks. Matrix metalloproteinase 9 (MMP-9) antisense oligonucleotides (ASO) or an MMP inhibitor were used to induce liver-selective MMP-9 inhibition. HFHF rats had mild, moderate, and severe steatosis, respectively, at 5, 10, and 15 weeks. I/R injury was enhanced in HFHF rats; this was accompanied by complete absence of hepatic vascular endothelial growth factor (VEGF)-stromal cell-derived factor 1 (sdf1) signaling, leading to lack of BM sproc recruitment. Liver-selective MMP-9 inhibition to protect against proteolytic cleavage of hepatic VEGF using either MMP-9 ASO or intraportal MMP inhibitor in 5-week and 10-week HFHF rats enhanced hepatic VEGF-sdf1 signaling, increased BM sproc recruitment, and reduced alanine aminotransferase (ALT) by 92% and 77% at 5 weeks and by 80% and 64% at 10 weeks of the HFHF diet, respectively. After I/R injury in 15-week HFHF rats, the MMP inhibitor reduced active MMP-9 expression by 97%, ameliorated histologic evidence of injury, and reduced ALT by 58%, which is comparable to control rats sustaining I/R injury. Rescue therapy with intraportal MMP inhibitor, given after ischemia, in the 5-week HFHF rat reduced ALT by 71% and reduced necrosis. CONCLUSIONS: Lack of signaling to recruit BM sprocs that repair injured LSECs renders steatotic liver more susceptible to I/R injury. Liver-selective MMP-9 inhibition enhances VEGF-sdf1 signaling and recruitment of BM sprocs, which markedly protects against I/R injury, even in severely steatotic rats.

Attenuation of the Köhler Effect in Racially Dissimilar Partnered Exercise Reversed Using Team Identity Strategy.

The authors describe two research experiments exploring the influence of race on the Köhler motivation gain effect with exercise tasks. Experiment 1 tested whether partner racial dissimilarity affects individual performance. Experiment 2 created a team identity recategorization intervention to potentially counter the influence on performance observed in Experiment 1. White male participants were partnered with either a Black or Asian partner (Experiment 1) or with a Black partner utilizing team names and shirt colors as a team identity recategorization strategy (Experiment 2). Racially dissimilar dyads completed two sets of abdominal plank exercises with a Köhler conjunctive task paradigm (stronger partner; team performance outcome dependent upon the weaker-ability participant's performance). The results of Experiment 1 suggest attenuation of the previously successful group motivation gain effect in the racially dissimilar condition. The simple recategorization strategy utilized in Experiment 2 appeared to reverse motivation losses under conjunctive-task conditions in racially dissimilar exercise dyads.

Exploring Readiness for Teleprecepting in Psychiatric Mental Health Nurse Practitioner Training.

OBJECTIVE: Telehealth offers a solution to many challenges in health care, including the shortage of psychiatric providers. Recently the need to limit patient and provider exposure to coronavirus disease 2019 (COVID-19) has escalated implementation of telehealth across the globe. As telehealth utilization expands, its role in nursing education and training requires systematic evaluation. Since publication of the National Organization of Nurse Practitioner Faculty white paper supporting telehealth in health care delivery and nurse practitioner education, several studies have demonstrated successful didactic instruction and training in telehealth. However, a recent literature review found no studies evaluating the use of telehealth technology as a means of precepting in clinical training. METHODS: This small-scale qualitative study investigates the readiness of one behavioral health clinic to provide teleprecepting to psychiatric mental health nurse practitioner students. Two preceptors and one student were interviewed using a peer-reviewed semistructured interview guide using video chat. Responses were reviewed, coded, and categorized into themes. RESULTS: Thematic analysis of the interviews revealed three categories for consideration in establishing teleprecepting. Clinical factors, logistics, and comparison with traditional precepting are discussed. Interviewees viewed teleprecepting as a viable method of increasing access to clinical training. CONCLUSIONS: This project supports teleprecepting as a feasible strategy for improving access to clinical training and as a technological resource that merits systematic evaluation. Practice guidelines are needed for teleprecepting of advanced practice registered nurse students, and both preceptors and students may benefit from training to support best practices prior to implementation.

The RNA polymerase III repressor MAF1 is regulated by ubiquitin-dependent proteasome degradation and modulates cancer drug resistance and apoptosis.

MAF1 homolog, negative regulator of RNA polymerase III (MAF1) is a key repressor of RNA polymerase (pol) III-dependent transcription and functions as a tumor suppressor. Its expression is frequently down-regulated in primary human hepatocellular carcinomas (HCCs). However, this reduction in MAF1 protein levels does not correlate with its transcript levels, indicating that MAF1 is regulated post-transcriptionally. Here, we demonstrate that MAF1 is a labile protein whose levels are regulated through the ubiquitin-dependent proteasome pathway. We found that MAF1 ubiquitination is enhanced upon mTOR complex 1 (TORC1)-mediated phosphorylation at Ser-75. Moreover, we observed that the E3 ubiquitin ligase cullin 2 (CUL2) critically regulates MAF1 ubiquitination and controls its stability and subsequent RNA pol III-dependent transcription. Analysis of the phenotypic consequences of modulating either CUL2 or MAF1 protein expression revealed changes in actin cytoskeleton reorganization and altered sensitivity to doxorubicin-induced apoptosis. Repression of RNA pol III-dependent transcription by chemical inhibition or knockdown of BRF1 RNA pol III transcription initiation factor subunit (BRF1) enhanced HCC cell sensitivity to doxorubicin, suggesting that MAF1 regulates doxorubicin resistance in HCC by controlling RNA pol III-dependent transcription. Together, our results identify the ubiquitin proteasome pathway and CUL2 as important regulators of MAF1 levels. They suggest that decreases in MAF1 protein underlie chemoresistance in HCC and perhaps other cancers and point to an important role for MAF1 and RNA pol III-mediated transcription in chemosensitivity and apoptosis.

VA-Community Dual Care: Veteran and Clinician Perspectives.

Many veterans receive care in both community settings and the VA. Recent legislation has increased veteran access to community providers, raising concerns about safety and coordination. This project aimed to understand the benefits and challenges of dual care from the perceptions of both the Veterans their clinicians. We conducted surveys and focus groups of veterans who use both VA and community care in VT and NH. We also conducted a web-based survey and a focus group involving primary care clinicians from both settings. The main measures included (1) reasons that veterans seek care in both settings; (2) problems faced by veterans and clinicians; (3) association of health status and ease of managing care with sites of primary care; and (4) association of veteran rurality with dual care experiences. The primary reasons veterans reported for using both VA and community care were (1) for convenience, (2) to access needed services, and (3) to get a second opinion. Veterans reported that community and VA providers were informed about the others' care more than half the time. Veterans in isolated rural towns reported better overall health and ease of managing their care. VA and community primary care clinicians reported encountering systems problems with dual-care including communicating medication changes, sharing lab and imaging results, communicating with specialists, sharing discharge summaries and managing medication renewals. Both Veterans and their primary clinicians report substantial system issues in coordinating care between the VA and the community, raising the potential for significant patient safety and Veteran satisfaction concerns.

Adolescent Patient Engagement Through Telepsychiatry: A Case Report Application.

The COVID-19 pandemic has changed psychopharmacological prescribing and management of patients around the world. Social distancing requirements led to a transition from face-to-face patient visits to telepsychiatry. Relaxed federal reimbursement policies during the COVID-19 pandemic expanded patient awareness and access to virtual care. For many psychiatric advanced practice RNs (APRNs), the transition to telepsychiatry was intended as a temporary solution until it is possible to return to in-person patient care. Instead, virtual care has become an expectation of patients and agencies. The current article presents a case study example of an adolescent psychiatric patient, exploring the challenges of therapeutic alliance, patient engagement, psychiatric evaluation, laboratory orders, deprescribing, and psychopharmacological adherence. The case study discusses considerations for APRNs who use telemental health in child and adolescent psychiatry and resources for clinical practice. [Journal of Psychosocial Nursing and Mental Health Services, 58(11), 9-12.].

Thinking Outside the Box: Are We Ready for Teleprecepting to Expand Training and Practice Venues?

A significant challenge related to nurse practitioner (NP) training is the shortage of clinical sites with qualified faculty to precept NP interns. The problem is compounded in rural communities with provider shortages, restricting their opportunities to train (and potentially recruit) new APRNs. Consequently, these underserved communities have difficulty accessing specialty providers, such as Psychiatric Mental Health Nurse Practitioners (PMHNPs). Combined with geographic distance from urban communities and generally lower pay, many rural and/or remote communities struggle with the disparity in contrast to more populated regions. A needs assessment of an underserved county with poor access to psychiatric services suggests that contracted telepsychiatry was costly and failed to address the long-term dearth of local psychiatric providers. Stakeholders reported that local RNs (and possibly FNPs) were employed by the local hospital and that a subgroup may have aptitude and interest in psychiatry if a university program and preceptors were available. Collaborating with an urban PMHNP program, televideo technology for clinical training and preceptor development offers a solution to the dearth of preceptors. A pilot intervention will use teleprecepting aimed at establishing best practice guidelines for implementation of this novel approach to expanding the clinical training and capacity in rural and under-served communities.

Ethnic socialization, ethnic identity, life satisfaction and school achievement of Roma ethnic minority youth.

This article is part of a Special Issue entitled Explaining Positive Adaptation of Immigrant Youth across Cultures. This study tested a mediation model of ethnic socialization (i.e., parental practices that promote children's knowledge about their history, heritage culture, cultural authenticity, and ethnic bias management) in Roma youth. Roma are the largest ethnic minority group in Europe subjected to severe discrimination, both currently and historically. Participants were 202 Roma youth aged 14 to 19 years old (M = 16.25, 53% females), who provided self-reports on their experience of ethnic socialization, ethnic identity, school achievement, and life satisfaction. Cultural pride reinforcement was related to better school achievement, whereas cultural coping with antagonism was positively related to life satisfaction. The study confirmed the model in that ethnic socialization was positively related to life satisfaction through effects on ethnic identity but negatively associated with school achievement. Findings have implications for adaptive cultural mechanisms promoting positive developmental outcomes among historically disadvantaged groups including those intersecting immigrant and multigenerational ethnic minority group categories.

T Cell Calcium Signaling Regulation by the Co-Receptor CD5.

Calcium influx is critical for T cell effector function and fate. T cells are activated when T cell receptors (TCRs) engage peptides presented by antigen-presenting cells (APC), causing an increase of intracellular calcium (Ca2+) concentration. Co-receptors stabilize interactions between the TCR and its ligand, the peptide-major histocompatibility complex (pMHC), and enhance Ca2+ signaling and T cell activation. Conversely, some co-receptors can dampen Ca2+ signaling and inhibit T cell activation. Immune checkpoint therapies block inhibitory co-receptors, such as cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and programmed death 1 (PD-1), to increase T cell Ca2+ signaling and promote T cell survival. Similar to CTLA-4 and PD-1, the co-receptor CD5 has been known to act as a negative regulator of T cell activation and to alter Ca2+ signaling and T cell function. Though much is known about the role of CD5 in B cells, recent research has expanded our understanding of CD5 function in T cells. Here we review these recent findings and discuss how our improved understanding of CD5 Ca2+ signaling regulation could be useful for basic and clinical research.

A retrospective analysis of feedlot morbidity and mortality outcomes in calves born to dams with known viral vaccination history.

This retrospective analysis aimed to determine the effects of a maternal viral vaccination program (MVVP; Express Verified) on calf health during the feeding period. In low- and high-risk populations, calves born to dams vaccinated pre-breeding with program products had improved morbidity and mortality outcomes compared with non-program animals.

Analyse rétrospective de la morbidité dans des parcs d'engraissement et résultats de mortalité chez les veaux nés de mères ayant des antécédents de vaccination connus. Cette analyse rétrospective visait à déterminer les effets d'un programme maternel de vaccination virale (PMVV; Express Verified) sur la santé des veaux durant la période d'allaitement. Dans les populations à risque faible et élevé, les veaux nés de mères vaccinées avant l'accouplement avec des produits de programme présentaient des résultats améliorés de morbidité et de mortalité comparativement aux animaux à l'extérieur du programme.(Traduit par Isabelle Vallières).

Maf1 is a novel target of PTEN and PI3K signaling that negatively regulates oncogenesis and lipid metabolism.

Maf1 was initially identified as a transcriptional repressor of RNA pol III-transcribed genes, yet little is known about its other potential target genes or its biological function. Here, we show that Maf1 is a key downstream target of PTEN that drives both its tumor suppressor and metabolic functions. Maf1 expression is diminished with loss of PTEN in both mouse models and human cancers. Consistent with its role as a tumor suppressor, Maf1 reduces anchorage-independent growth and tumor formation in mice. PTEN-mediated changes in Maf1 expression are mediated by PTEN acting on PI3K/AKT/FoxO1 signaling, revealing a new pathway that regulates RNA pol III-dependent genes. This regulatory event is biologically relevant as diet-induced PI3K activation reduces Maf1 expression in mouse liver. We further identify lipogenic enzymes as a new class of Maf1-regulated genes whereby Maf1 occupancy at the FASN promoter opposes SREBP1c-mediated transcription activation. Consistent with these findings, Maf1 inhibits intracellular lipid accumulation and increasing Maf1 expression in mouse liver abrogates diet-mediated induction of lipogenic enzymes and triglycerides. Together, these results establish a new biological role for Maf1 as a downstream effector of PTEN/PI3K signaling and reveal that Maf1 is a key element by which this pathway co-regulates lipid metabolism and oncogenesis.

Characterization of lipid metabolism in a novel immortalized human hepatocyte cell line.

The development of hepatocyte cell models that represent fatty acid partitioning within the human liver would be beneficial for the study of the development and progression of nonalcoholic fatty liver disease (NAFLD). We sought to develop and characterize a novel human liver cell line (LIV0APOLY) to establish a model of lipid accumulation using a physiological mixture of fatty acids under low- and high-glucose conditions. LIV0APOLY cells were compared with a well-established cell line (HepG2) and, where possible, primary human hepatocytes. LIV0APOLY cells were found to proliferate and express some mature liver markers and were wild type for the PNPLA3 (rs738409) gene, whereas HepG2 cells carried the Ile(148)Met variant that is positively associated with liver fat content. Intracellular triglyceride content was higher in HepG2 than in LIV0APOLY cells; exposure to high glucose and/or exogenous fatty acids increased intracellular triglyceride in both cell lines. Triglyceride concentrations in media were higher from LIV0APOLY compared with HepG2 cells. Culturing LIV0APOLY cells in high glucose increased a marker of endoplasmic reticulum stress and attenuated insulin-stimulated Akt phosphorylation whereas low glucose and exogenous fatty acids increased AMPK phosphorylation. Although LIV0APOLY cells and primary hepatocytes stored similar amounts of exogenous fatty acids as triglyceride, more exogenous fatty acids were partitioned toward oxidation in the LIV0APOLY cells than in primary hepatocytes. LIV0APOLY cells offer the potential to be a renewable cellular model for studying the effects of exogenous metabolic substrates on fatty acid partitioning; however, their usefulness as a model of lipoprotein metabolism needs to be further explored.

'They don't look at what affects us': the role of ecodevelopmental factors on alcohol and drug use among Latinos with physical disabilities.

Objectives. Latinos with disabilities disproportionately report substance use, including binge drinking and drug use. Ecodevelopmental factors, including socioeconomic patterning of poverty, social exclusion, and post-colonial racism, have been shown to impact alcohol and drug use. However, this line of research remains underdeveloped among Latinos with disabilities. The purpose of this study was to obtain rich descriptions of the role of ecodevelopmental factors, including family and community, on alcohol and drug use among Latinos with physical disabilities. Methods. We utilized a community-based participatory research design, in conjunction with an innovative methodology referred to as photovoice. Three rounds of photography and focus group interviews were conducted with a total of 17 focus groups. Reflections in each focus group interview were aloud and digitally audiotaped. A total of 28 participants 19-35 years of age (mean age = 27.65, SD = 5.48) participated in each round of photography and focus group interviews. Data analyses followed the tenets of descriptive phenomenology. Results. Findings highlight ecodevelopmental family and community risk and protective factors. At the family level, participants reflected on the ways in which family functioning, including family support, communication, and cohesion, can serve as risk and promotive factors for alcohol and drug use. Additionally, participants described in detail how experiences of poverty, stigma and discrimination, violence, accessibility to alcohol and drugs, accessibility for persons with disabilities, transportation, community support and cohesion, and access to health and mental health services constitute risk and promotive factors at the community level. Conclusion. Findings are suggestive of how ecodevelopmental family and community factors might increase the risk of alcohol and drug use among Latinos with physical disabilities. From this qualitative research, we derive a series of testable hypotheses. For example, future studies should examine the impact of family functioning on alcohol and drug use among Latinos with physical disabilities over time. Study findings may have great utility to inform the development of preventive interventions for this at-risk group.

The Incidence of Furcation Region Patency in Molars Before and After Simulated Periodontal Therapy.

PURPOSE: To determine if there is increased bacterial communication through the furcation region in molar teeth after simulated periodontal therapy. METHODS: Sixty-five extracted first and second molars were accessed and the roots were sectioned 4 mm apical to the furcation. The canals and external suface of the root were sealed except the furcation region. In Phase I, the teeth were sterilized and then suspended in Rogosa SL broth. A broth containing Lactobacillus casei was placed in the pulp chamber. The Rogosa SL broth in the bottom chamber was monitored daily for 30 days for turbidity, and once turbidly was noted, the broth was plated to confirm the presence of L. casei. In Phase II, the furcation regions were scaled and cementum removed, the teeth were sterilized, and the microbial leakage was repeated. RESULTS: The Phase I and Phase II median times to turbidity were 9.5 days and 4 days, respectively, and the difference was statistically significant (p = 0.0035). Phase I turbidity rate was 86.5%, and Phase II was 92.3%, which was not statistically significant (p = 0.25). CONCLUSIONS: The root canal system communicated with the furcation region an average of 86.5% and 92.5% after scaling and root planing during the 30 days of the experiment. The time of leakage between the two groups decreased from 9.5 to 4 days (p = 0.0035). CLINICAL SIGNIFICANCE: Periodontal instrumentation of the furcation region in molar teeth can increase the risk of bacterial contamination by 39% while shortening the time for bacterial penetration in teeth with exposed dentin or furcation canals. accessory canals, scaling, and root planing.

Covalent small ubiquitin-like modifier (SUMO) modification of Maf1 protein controls RNA polymerase III-dependent transcription repression.

RNA polymerase (pol) III transcribes genes that determine biosynthetic capacity. Induction of these genes is required for oncogenic transformation. The transcriptional repressor, Maf1, plays a central role in the repression of these and other genes that promote oncogenesis. Our studies identify an important new role for SUMOylation in repressing RNA pol III-dependent transcription. We show that a key mechanism by which this occurs is through small ubiquitin-like modifier (SUMO) modification of Maf1 by both SUMO1 and SUMO2. Mutation of each lysine residue revealed that Lys-35 is the major SUMOylation site on Maf1 and that the deSUMOylase, SENP1, is responsible for controlling Maf1K35 SUMOylation. SUMOylation of Maf1 is unaffected by rapamycin inhibition of mammalian target of rapamycin (mTOR) and mTOR-dependent Maf1 phosphorylation. By preventing SUMOylation at Lys-35, Maf1 is impaired in its ability to both repress transcription and suppress colony growth. Although SUMOylation does not alter Maf1 subcellular localization, Maf1K35R is defective in its ability to associate with RNA pol III. This impairs Maf1 recruitment to tRNA gene promoters and its ability to facilitate the dissociation of RNA pol III from these promoters. These studies identify a novel role for SUMOylation in controlling Maf1 and RNA pol III-mediated transcription. Given the emerging roles of SENP1, Maf1, and RNA pol III transcription in oncogenesis, our studies support the idea that deSUMOylation of Maf1 and induction of its gene targets play a critical role in cancer development.

Treatment of amalgam tattoo with a subepithelial connective tissue graft and acellular dermal matrix.

A 54-year-old female was referred for management of a large amalgam tattoo involving the alveolar mucosa between teeth #6 and #9. The lesion had been present for over 20 years following endodontic treatment of teeth #7 and #8. A two-stage surgical approach was used to remove the pigmentation, beginning with removal of amalgam fragments from the underlying bone and placement of a subepithelial connective tissue graft and acellular dermal matrix to increase soft tissue thickness subadjacent to the amalgam. Following 7 weeks of healing, gingivoplasty was performed to remove the overlying pigmented tissue. At the 21-month follow-up appointment, the patient exhibited naturally appearing soft tissue with no evidence of amalgam tattoo.