Necrotizing fasciitis of the head and neck in era of COVID-19: a single-institution experience.

Objectives: Necrotizing fasciitis (NF) of the head and neck is a critical condition, known for its severe impact and high mortality rates, often linked with diabetes, odontogenic infections, and immunosuppression. Observations from the University of Ottawa's Department of Otolaryngology - Head and Neck Surgery indicate an increase in NF cases since the COVID-19 pandemic began, suggesting a possible association between COVID-19 and NF. This study aims to assess the incidence of NF since the pandemic's onset and explore its association with COVID-19. Design: Conducted as a single-center retrospective review from January 1, 2015 to April 7, 2023, this study included patients aged over 18 years with histopathologic confirmation of NF, analyzing clinical risk factors, treatment, and outcomes. Patients were divided into pre- and post-COVID-19 groups for comparison. Results: Of 16 patients, 68.7% were in the post-COVID-19 group, with a notable increase in 2022. The most common risk factors were diabetes mellitus (43.8%) and history of odontogenic infection or extraction (31.3%). Only one patient (6.3%) presented with concomitant COVID-19 infection and NF. All patients underwent treatment with serial surgical debridement and intravenous antibiotics with mortality rates rising to 12.5% after the pandemic. Conclusions: Our study demonstrates an increased incidence of NF cases in our institution after the COVID-19 pandemic.

Elevated oxidative stress biomarkers in adults with segmented sleep patterns.

STUDY OBJECTIVES: We investigated the association between different sleep patterns and inflammatory and oxidative stress biomarkers in adults. METHODS: A total of 321 consented adults who fulfilled the inclusion criteria were recruited in this cross-sectional study. The inclusion criteria were mainly based on apparently healthy adults aged 18-59 years. To identify sleep patterns, participants were requested to wear the actigraph for 1 week for 24 hours a day. Fasting blood was collected from each participant at day 8. The blood serum was analyzed for inflammatory and oxidative stress biomarkers. Sleep patterns were defined as monophasic (1 episode of night sleep) biphasic (2 episodes of sleep; night and aternoon siesta), and polyphasic sleep pattern (3 or more sleep episodes). RESULTS: There was no correlation between night sleep duration, total sleep in 24 hours, and napping among inflammatory and oxidative stress biomarkers: high-sensitivity C-reactive protein, malondialdehyde, total glutathione, and basal oxidizability status. Actigraphy reports showed 3 sleep patterns in this cohort, monophasic (24.3%), biphasic-napping (45.2%) and polyphasic (30.5%). Individuals with segmented sleep patterns were significantly associated with oxidative stress biomarkers. A polyphasic sleep pattern was significantly associated with higher basal oxidizability status (P = .023), whereas a biphasic sleep pattern showed higher malondialdehyde (P = .036) as compared to a monophasic sleep pattern. Total glutathione was significantly higher in monophasic sleepers (P = .046). There was no difference in serum high-sensitivity C-reactive protein among all sleep patterns. CONCLUSIONS: Segmented sleep in polyphasic and biphasic sleep patterns is associated with higher serum malondialdehyde and basal oxidizability status in particular. Further studies are recommended on the cardiometabolic impact of oxidative stress biomarkers in individuals with segmented sleep. CITATION: Al Lawati I, Zadjali F, Al-Abri MA. Elevated oxidative stress biomarkers in adults with segmented sleep patterns. J Clin Sleep Med. 2024;20(6):959-966.

Base of the tongue hyalinizing clear cell carcinoma: Case report and literature review.

Hyalinizing clear cell carcinoma is an uncommon neoplasm arising in minor salivary glands. We present a rare case of hyalinizing clear cell carcinoma in the base of the tongue. We report a case of a 38-year-old female presented with a progressive history of hemoptysis and dysphagia over the course of 4 years. Examination revealed a mass originating from the base of the tongue with a biopsy confirmed as hyalinizing clear cell carcinoma . An Ovid MEDLINE and PubMed literature review was conducted due to the rarity of this type of tumor. The patient underwent surgical excision with immediate reconstruction with radial forearm free flap followed with adjuvant radiotherapy and was disease free at her most recent follow-up (12 months). Our review included a total of 13 new cases, including our case. The majority of the cases presented with dysphagia. Surgical excision is the mainstay of treatment, and overall these patients have a good prognosis. Our case highlights a rare presentation of hyalinizing clear cell carcinoma of the base of the tongue, successfully treated with surgical excision, free tissue reconstruction and adjuvant radiotherapy.

Cytotoxicity, mutagenicity and genotoxicity of electronic cigarettes emission aerosols compared to cigarette smoke: the REPLICA project.

Concerns have recently increased that the integrity of some scientific research is questionable due to the inability to reproduce the claimed results of some experiments and thereby confirm that the original researcher's conclusions were justified. This phenomenon has been described as 'reproducibility crisis' and affects various fields from medicine to basic applied sciences. In this context, the REPLICA project aims to replicate previously conducted in vitro studies on the toxicity of cigarette smoke and e-cigarette aerosol, sometimes adding experiments or conditions where necessary, in order to verify the robustness and replicability of the data. In this work the REPLICA Team replicated biological and toxicological assessment published by Rudd and colleagues in 2020. As in the original paper, we performed Neutral Red Uptake (NRU) assay for the evaluation of cytotoxicity, Ames test for the evaluation of mutagenesis and In Vitro Micronuclei (IVMN) assay for the evaluation of genotoxicity on cells treated with cigarette smoke or e-cigarette aerosol. The results showed high cytotoxicity, mutagenicity and genotoxicity induced by cigarette smoke, but slight or no cytotoxic, mutagenic and genotoxic effects induced by the e-cigarette aerosol. Although the two studies presented some methodological differences, the findings supported those previously presented by Rudd and colleagues.

Seasonal variation and sleep patterns in a hot climate Arab Region.

PURPOSE: To describe the effect of seasonal variations on sleep patterns in a hot climate Arab region. METHODS: This is a cross-sectional study that included healthy Omani subjects of both genders between ages 18 and 59 years. Data for sleep pattern identification in summer and winter were collected from participants using an actigraphy wristband. RESULTS: Among 321 participants, in summer seasons, a polyphasic sleep pattern (40%) prevailed over other sleep patterns (P < 0.001). While in the winter season, monophasic sleep (31%) was the dominant pattern (P < 0.001). Subjects slept longer during the winter seasons with total hours of sleep during the day 48 min longer than in the summer, though the difference was not statistically significant (P > 0.05), while siesta duration in the summer was significantly longer (13 min, P < 0.01). In summer, the sleep quality was good (PSQI ≤ 5); however, it was poor (PSQI > 5) in winter (P < 0.05). Night sleep duration, daytime sleepiness, and sleep latency were not statistically different between the summer and winter seasons. CONCLUSION: Sleep patterns may be influenced by seasonal changes. A polyphasic sleep pattern prevailed in summer while a monophasic pattern was the predominant sleep pattern in winter. In summer, the sleep quality was good and the siesta duration was longer compared to the winter.

Single Gene Mutations in Pkd1 or Tsc2 Alter Extracellular Vesicle Production and Trafficking.

Patients with autosomal dominant polycystic kidney disease (ADPKD) and tuberous sclerosis complex (TSC) are born with normal or near-normal kidneys that later develop cysts and prematurely lose function. Both renal cystic diseases appear to be mediated, at least in part, by disease-promoting extracellular vesicles (EVs) that induce genetically intact cells to participate in the renal disease process. We used centrifugation and size exclusion chromatography to isolate the EVs for study. We characterized the EVs using tunable resistive pulse sensing, dynamic light scattering, transmission electron microscopy, and Western blot analysis. We performed EV trafficking studies using a dye approach in both tissue culture and in vivo studies. We have previously reported that loss of the Tsc2 gene significantly increased EV production and here demonstrate that the loss of the Pkd1 gene also significantly increases EV production. Using a cell culture system, we also show that loss of either the Tsc2 or Pkd1 gene results in EVs that exhibit an enhanced uptake by renal epithelial cells and a prolonged half-life. Loss of the primary cilia significantly reduces EV production in renal collecting duct cells. Cells that have a disrupted Pkd1 gene produce EVs that have altered kinetics and a prolonged half-life, possibly impacting the duration of the EV cargo effect on the recipient cell. These results demonstrate the interplay between primary cilia and EVs and support a role for EVs in polycystic kidney disease pathogenesis.

Tsc2 mutation induces renal tubular cell nonautonomous disease.

TSC renal cystic disease is poorly understood and has no approved treatment. In a new principal cell-targeted murine model of Tsc cystic disease, the renal cystic epithelium is mostly composed of type A intercalated cells with an intact Tsc2 gene confirmed by sequencing, although these cells exhibit a Tsc-mutant disease phenotype. We used a newly derived targeted murine model in lineage tracing and extracellular vesicle (EV) characterization experiments and a cell culture model in EV characterization and cellular induction experiments to understand TSC cystogenesis. Using lineage tracing experiments, we found principal cells undergo clonal expansion but contribute very few cells to the cyst. We determined that cystic kidneys contain more interstitial EVs than noncystic kidneys, excrete fewer EVs in urine, and contain EVs in cyst fluid. Moreover, the loss of Tsc2 gene in EV-producing cells greatly changes the effect of EVs on renal tubular epithelium, such that the epithelium develops increased secretory and proliferative pathway activity. We demonstate that the mTORC1 pathway activity is independent form the EV production, and that the EV effects for a single cell line can vary significantly. TSC cystogenesis involves significant contribution from genetically intact cells conscripted to the mutant phenotype by mutant cell derived EVs.

Electronic nicotine delivery systems exhibit reduced bronchial epithelial cells toxicity compared to cigarette: the Replica Project.

Electronic nicotine delivery systems (ENDS) may reduce health risks associated with chronic exposure to smoke and their potential benefits have been the matter of intense scientific debate. We aimed to replicate three published studies on cytotoxic and inflammatory effects of cigarette smoke and ENDS aerosol in an independent multi-center ring study. We aimed to establish the reliability of results and the robustness of conclusions by replicating the authors' experimental protocols and further validating them with different techniques. Human bronchial epithelial cells (NCI-H292) were exposed to cigarette whole smoke and vapor phase and to aerosol from ENDS. We also assessed the inflammatory cytokines interleukin-6 and interleukin-8 and the remodeling mediator matrix metalloproteinase-1. We replicated cell viability results and confirmed that almost 80% of cytotoxic effects are due to volatile compounds in the vapor phase of smoke. Our findings substantiated the reduced cytotoxic effects of ENDS aerosol. However, our data on inflammatory and remodeling activity triggered by smoke differed significantly from those in the original reports. Taken together, independent data from multiple laboratories clearly demonstrated the reduced toxicity of ENDS products compared to cigarettes.

Renal cystic disease in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is associated with TSC1 or TSC2 gene mutations resulting in hyperactivation of the mTORC1 pathway. This mTORC1 activation is associated with abnormal tissue development and proliferation such that in the kidney there are both solid tumors and cystic lesions. This review summarizes recent advances in tuberous sclerosis complex nephrology and focuses on the genetics and cell biology of tuberous sclerosis complex renal disease, highlighting a role of extracellular vesicles and the innate immune system in disease pathogenesis.

Connections between prolactin and ovarian cancer.

Ovarian cancer (OC) is characterized by a high morbidity and mortality, highlighting a great need for a better understanding of biological mechanisms that affect OC progression and improving its early detection methods. This study investigates effects of prolactin (PRL) on ovarian cancer cells, analyzes PRL receptors (PRLR) in tissue micro arrays and relates PRLR expression to survival of ovarian cancer. A database, composed of transcript profiles from OC, was searched for PRLR expression and results were put in relation to survival. Expression of PRLR in OC tissue sections and OC cell lines SKOV3, OV2008 and OVSAHO was assessed using immunohistochemistry, western blots and quantitative real-time PCR. The biological function of PRLR was evaluated by proliferation, colony formation and wound healing assays. Levels of PRLR mRNA are related to survival; in epithelial OC a high PRLR mRNA expression is related to a shorter survival. Analysis of a tissue micro array consisting of 84 OC showed that 72% were positive for PRLR immuno-staining. PRLR staining tended to be higher in OC of high grade tumors compared to lower grades. PRLR mRNA and protein can further be detected in OC cell lines. Moreover, in vitro treatment with PRL significantly activated the JAK/STAT pathway. PRLR expression is associated with OC survivals. PRL and its receptor may play an onco-modulatory role and promote tumor aggressiveness in OC. Alternatively, increased PRLR levels may form a base for the development of PRLR antagonist or PRLR antagonist-drug conjugate to increase selective uptake of anti-cancer drugs.

An engineered microfluidic blood-brain barrier model to evaluate the anti-metastatic activity of ß-boswellic acid.

BACKGROUND: The development of anti-cancer drugs with the ability to inhibit brain metastasis through the blood-brain barrier (BBB) is substantially limited due to the lack of reliable in vitro models. MAIN METHODS: In this study, the Geltrex-based Transwell and microfluidic BBB models were applied to screen the effect of ß-boswellic acid (ß-BA) on the metastasis of MDA-MB-231 cells through the BBB in static and dynamic conditions, respectively. MAJOR RESULTS: The toxicity assay revealed that ß-BA deteriorates MDA-MB-231 cells, while ß-BA had no detectable toxic effects on human umbilical vein endothelial cells (HUVECs) and astrocytes. Trans-endothelial electrical resistance evaluation showed sustainable barrier integrity upon treatment with ß-BA. Vimentin expression in HUVECs, evaluated using western blot, confirmed superior barrier integrity in the presence of ß-BA. The obtained results were confirmed using an invasion study with a cell tracker and a scanning electron microscope. ß-BA significantly inhibited metastasis by 85%, while cisplatin (Cis), a positive control, inhibited cancer cell migration by 12% under static conditions. Upon applying a dynamic BBB model, it was revealed that ß-BA-mediated metastasis inhibition was significantly higher than that mediated by Cis. CONCLUSIONS AND IMPLICATIONS:  In summary, the current study proved the anti-metastatic potential of ß-BA in both static and dynamic BBB models.

Familial Hypercholesterolemia in the Arabian Gulf Region: Clinical results of the Gulf FH Registry.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a common autosomal dominant disorder that can result in premature atherosclerotic cardiovascular disease (ASCVD). Limited data are available worldwide about the prevalence and management of FH. Here, we aimed to estimate the prevalence and management of patients with FH in five Arabian Gulf countries (Saudi Arabia, Oman, United Arab Emirates, Kuwait, and Bahrain). METHODS: The multicentre, multinational Gulf FH registry included adults (≥18 years old) recruited from outpatient clinics in 14 tertiary-care centres across five Arabian Gulf countries over the last five years. The Gulf FH registry had four phases: 1- screening, 2- classification based on the Dutch Lipid Clinic Network, 3- genetic testing, and 4- follow-up. RESULTS: Among 34,366 screened patient records, 3713 patients had suspected FH (mean age: 49±15 years; 52% women) and 306 patients had definite or probable FH. Thus, the estimated FH prevalence was 0.9% (1:112). Treatments included high-intensity statin therapy (34%), ezetimibe (10%), and proprotein convertase subtilisin/kexin type 9 inhibitors (0.4%). Targets for low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol were achieved by 12% and 30%, respectively, of patients at high ASCVD risk, and by 3% and 6%, respectively, of patients at very high ASCVD risk (p <0.001; for both comparisons). CONCLUSIONS: This snap-shot study was the first to show the high estimated prevalence of FH in the Arabian Gulf region (about 3-fold the estimated prevalence worldwide), and is a "call-to-action" for further confirmation in future population studies. The small proportions of patients that achieved target LDL-C values implied that health care policies need to implement nation-wide screening, raise FH awareness, and improve management strategies for FH.

Agreement analysis of sleep patterns between self-reported questionnaires and actigraphy in adults.

PURPOSE: To investigate the agreement in sleep pattern recording by self-reported sleep questionnaires and actigraphy in adults. METHODS: This is a cross-sectional study. Men and women who met inclusion criteria were recruited for this study. The inclusion criteria were apparently healthy Omani nationals ages 19 to 50 years. Sleep questionnaires were randomly distributed in Muscat either directly or via electronic and paper announcements. Data were collected from the participants using the self-reported questionnaires with four piloted questions for sleep pattern identification and through the actigraphy wristband given to subjects to wear for a week. Cohen's kappa test was performed for agreement analysis. RESULTS: A total of 964 Omani subjects between ages 18 and 59 years of both genders were recruited and completed the questionnaires successfully. Out of these, only 321 subjects wore the actigraphy wristband for 1 week (response rate = 33%). Agreement analysis reported a mild level of agreement for the monophasic (41%), moderate level for biphasic (59%), and good level for polyphasic (70%) sleep patterns. The overall agreement level of sleep patterns between the two methods was 57%. There is a low specificity of self-reported assessment in reporting sleep pattern. CONCLUSION: The average agreement level of subjective versus objective assessments of sleep patterns was moderate at 57% and self-reported sleep pattern is not specific. The study recommends the use of actigraphy along with sleep questionnaires for accurate assessment of sleep patterns in cohort studies.

New derivatives of 11-keto-ß-boswellic acid (KBA) induce apoptosis in breast and prostate cancers cells.

A series of new 11-keto-ß-boswellic acid were partially-synthesized by modifying the hydroxyl and carboxylic acid functional groups of ring A. The structures of the new analogs were confirmed by detailed spectral data analysis. Compounds 4, 5 and 9 exhibited potent anti-cancer results against two human tumor cancer cell lines having IC50 value of MCF-7 (breast) and LNCaP (prostate): 123.6, 9.6 and 88.94 µM and 9.6, 44.12 and 12.03 µM, respectively. Additionally, a maximum nuclear fragmentation was observed for 4 (78.44%) in AKBA treated cells after 24 hr followed by 5 and 9 with (74.25 and 66.9% respectively). This study suggests that the presence of hydrazone functionality (4 and 9) has effectively improved the potency of AKBA. Interestingly, compound 5 with a lost carboxylic acid group of ring A showed comparable potent activity. Highly selective AKBA requires further modification to improve its bioavailability and solubility inside the cancer cells.

Sleep Patterns and Quality in Omani Adults.

BACKGROUND: Sleep patterns have changed continuously worldwide and it can be influenced by social, cultural, and environmental factors. These patterns may be associated with poor sleep quality and daytime sleepiness. The aim of the study was to investigate sleep patterns and quality in Omani adults using actigraphy. SUBJECTS AND METHODS: This was a cross-sectional study conducted between June 2015 and February 2017. Four hundred subjects agreed to participate in the study (52% male, 48% female). Subjects were randomly selected and enrolled in the study among young adults and middle aged individuals living in the City of Muscat. Subjects were asked to fill-in Epworth sleepiness scale (ESS) and Pittsburgh sleep quality index (PSQI). Actigraphy was used to measure their sleep patterns for one week. RESULTS: The mean age of participants was 32.80±11.50 years. Four sleep patterns were identified: monophasic, bi-phasic (post-dawn), bi-phasic (afternoon siesta), and polyphasic (three sleep periods/24 hours). The study revealed that 35% of participants had biphasic-siesta sleep pattern, 28% polyphasic, 26% monophasic, and 11% biphasic-dawn. The biphasic siesta pattern was found to be associated with younger age group (25-34 years) (P=0.001). Polyphasic sleep was associated with higher ESS score (P=0.001) but not with poor sleep quality (P=0.24). There was no significant difference in night sleep duration among all the sleep patterns (P=0.07) but the polyphasic sleep pattern had higher total 24-hour day sleep duration (P=0.03). Nearly 90% of participants practiced afternoon siestas with mean duration of 45±43 minutes. CONCLUSION: The predominant sleep pattern among Omanis was biphasic-siesta and majority of people practiced afternoon siesta. Polyphasic sleep pattern is associated with daytime sleepiness.

Tuberous Sclerosis Complex Axis Controls Renal Extracellular Vesicle Production and Protein Content.

The tuberous sclerosis complex (Tsc) proteins regulate the conserved mTORC1 growth regulation pathway. We identified that loss of the Tsc2 gene in mouse inner medullary collecting duct (mIMCD) cells induced a greater than two-fold increase in extracellular vesicle (EV) production compared to the same cells having an intact Tsc axis. We optimized EV isolation using a well-established size exclusion chromatography method to produce high purity EVs. Electron microscopy confirmed the purity and spherical shape of EVs. Both tunable resistive pulse sensing (TRPS) and dynamic light scattering (DLS) demonstrated that the isolated EVs possessed a heterogenous size distribution. Approximately 90% of the EVs were in the 100-250 nm size range, while approximately 10% had a size greater than 250 nm. Western blot analysis using proteins isolated from the EVs revealed the cellular proteins Alix and TSG101, the transmembrane proteins CD63, CD81, and CD9, and the primary cilia Hedgehog signaling-related protein Arl13b. Proteomic analysis of EVs identified a significant difference between the Tsc2-intact and Tsc2-deleted cell that correlated well with the increased production. The EVs may be involved in tissue homeostasis and cause disease by overproduction and altered protein content. The EVs released by renal cyst epithelia in TSC complex may serve as a tool to discover the mechanism of TSC cystogenesis and in developing potential therapeutic strategies.

The Gulf Familial Hypercholesterolemia Registry (Gulf FH): Design, Rationale and Preliminary Results.

AIM: To determine the prevalence, genetic characteristics, current management and outcomes of familial hypercholesterolaemia (FH) in the Gulf region. METHODS: Adult (18-70 years) FH patients were recruited from 9 hospitals and centres across 5 Arabian Gulf countries. The study was divided into 4 phases and included patients from 3 different categories. In phase 1, suspected FH patients (category 1) were collected according to the lipid profile and clinical data obtained through hospital record systems. In phase 2, patients from category 2 (patients with a previous clinical diagnosis of FH) and category 1 were stratified into definitive, probable and possible FH according to the Dutch Lipid Clinic Network criteria. In phase 3, 500 patients with definitive and probable FH from categories 1 and 2 will undergo genetic testing for 4 common FH genes. In phase 4, these 500 patients with another 100 patients from category 3 (patients with previous genetic diagnosis of FH) will be followed for 1 year to evaluate clinical management and cardiovascular outcomes. The Gulf FH cohort was screened from a total of 34,366 patients attending out-patient clinics. RESULTS: The final Gulf FH cohort consisted of 3,317 patients (mean age: 47±12 years, 54% females). The number of patients with definitive FH is 203. In this initial phase of the study, the prevalence of (probable and definite) FH is 1/232. CONCLUSION: The prevalence of FH in the adult population of the Arabian Gulf region is high. The Gulf FH registry, a first-of-a-kind multi-national study in the Middle East region, will help in improving underdiagnosis and undertreatment of FH in the region.

Tuberous sclerosis complex exhibits a new renal cystogenic mechanism.

Tuberous sclerosis complex (TSC) is a tumor predisposition syndrome with significant renal cystic and solid tumor disease. While the most common renal tumor in TSC, the angiomyolipoma, exhibits a loss of heterozygosity associated with disease, we have discovered that the renal cystic epithelium is composed of type A intercalated cells that have an intact Tsc gene that have been induced to exhibit Tsc-mutant disease phenotype. This mechanism appears to be different than that for ADPKD. The murine models described here closely resemble the human disease and both appear to be mTORC1 inhibitor responsive. The induction signaling driving cystogenesis may be mediated by extracellular vesicle trafficking.

The ubiquitin ligase Cullin5SOCS2 regulates NDR1/STK38 stability and NF-κB transactivation.

SOCS2 is a pleiotropic E3 ligase. Its deficiency is associated with gigantism and organismal lethality upon inflammatory challenge. However, mechanistic understanding of SOCS2 function is dismal due to our unawareness of its protein substrates. We performed a mass spectrometry based proteomic profiling upon SOCS2 depletion and yield quantitative data for ~4200 proteins. Through this screen we identify a novel target of SOCS2, the serine-threonine kinase NDR1. Over-expression of SOCS2 accelerates turnover, while its knockdown stabilizes, endogenous NDR1 protein. SOCS2 interacts with NDR1 and promotes its degradation through K48-linked ubiquitination. Functionally, over-expression of SOCS2 antagonizes NDR1-induced TNFα-stimulated NF-κB activity. Conversely, depletion of NDR1 rescues the effect of SOCS2-deficiency on TNFα-induced NF-κB transactivation. Using a SOCS2-/- mice model of colitis we show that SOCS2-deficiency is pro-inflammatory and negatively correlates with NDR1 and nuclear p65 levels. Lastly, we provide evidence to suggest that NDR1 acts as an oncogene in prostate cancer. To the best of our knowledge, this is the first report of an identified E3 ligase for NDR1. These results might explain how SOCS2-deficiency leads to hyper-activation of NF-κB and downstream pathological implications and posits that SOCS2 induced degradation of NDR1 may act as a switch in restricting TNFα-NF-κB pathway.