DUOX, a member of the NADPH oxidase family, acts as the first line of defense against enteric pathogens by producing microbicidal reactive oxygen species. DUOX is activated upon enteric infection, but the mechanisms regulating DUOX activity remain incompletely understood. Using Drosophila genetic tools, we show that enteric infection results in "pro-catabolic" signaling that initiates metabolic reprogramming of enterocytes toward lipid catabolism, which ultimately governs DUOX homeostasis. Infection induces signaling cascades involving TRAF3 and kinases AMPK and WTS, which regulate TOR kinase to control the balance of lipogenesis versus lipolysis. Enhancing lipogenesis blocks DUOX activity, whereas stimulating lipolysis via ATG1-dependent lipophagy is required for DUOX activation. Drosophila with altered activity in TRAF3-AMPK/WTS-ATG1 pathway components exhibit abolished infection-induced lipolysis, reduced DUOX activation, and enhanced susceptibility to enteric infection. Thus, this work uncovers signaling cascades governing inflammation-induced metabolic reprogramming and provides insight into the pathophysiology of immune-metabolic interactions in the microbe-laden gut epithelia.

Differential diagnosis of posterior neck pain is very challenging based on symptoms and physical examination only. Retropharyngeal calcific tendinitis is a rare and frequently misdiagnosed entity in various causes of neck pain. It results from calcium hydroxyapatite deposition in the longus colli muscle which is characterized by severe neck pain, painful restriction of neck movement, dysphagia, and odynophagia. We herein report a case of a patient with acute retropharyngeal calcific tendinitis, who complained of posterior neck pain, initially diagnosed and treated as a myofascial neck pain syndrome.

SIRT1, the NAD(+)-dependent protein deacetylase, controls cell-cycle progression and apoptosis by suppressing p53 tumour suppressor. Although SIRT1 is known to be phosphorylated by JNK1 upon oxidative stress and subsequently down-regulated, it still remains elusive how SIRT1 stability and activity are controlled. Here, we have unveiled that CHFR functions as an E3 Ub-ligase of SIRT1, responsible for its proteasomal degradation under oxidative stress conditions. CHFR interacts with and destabilizes SIRT1 by ubiquitylation and subsequent proteolysis. Such CHFR-mediated SIRT1 inhibition leads to the increase of p53 acetylation and its target gene transcription. Notably, CHFR facilitates SIRT1 destabilization when SIRT1 is phosphorylated by JNK1 upon oxidative stress, followed by prominent apoptotic cell death. Meanwhile, JNK inhibitor prevents SIRT1 phosphorylation, leading to elevated SIRT1 protein levels even in the presence of H2O2. Taken together, our results indicate that CHFR plays a crucial role in the cellular stress response pathway by controlling the stability and function of SIRT1.

Objective: Several factors associated with referral time to hospice and/or palliative care services have been identified, but there is no literature on the association between these services and the emotional status of the family caregivers (FCs). This article is intended to address that issue.Method: A semistructured interview was employed to collect data for a retrospective cohort study. The primary FCs of terminally ill cancer patients were interviewed at the time of the patient's referral to the palliative care unit. Interview data were combined with patients' medical record data for our analysis. The emotional status of the FCs was categorized into one of three groups according to their responses to the anticipated death of their family member: acceptance, anxious/depressed, and denial/angry. A Cox proportional hazard model was used to examine and identify the factors related to the length of stay (LOS) in the palliative care unit.Results: A total of 198 patient-FC pairs were identified. The median LOS was 18 days. A multivariate analysis with adjustment for potential variables revealed significant differences in LOS according to cancer type and time since cancer diagnosis. The denial/angry FC category was independently associated with a shorter LOS (vs. acceptance, adjusted hazard ratio (aHR) 2.11; 95% confidence interval (CI), 1.11-4.03).Significance of Results: We found that terminally ill cancer patients who were referred late had FCs who were in denial or were angry about the anticipated death of their loved one. The emotional status of FCs should be considered when patients with terminal cancer are referred to palliative care.

The Hippo pathway plays crucial roles in regulating organ size and stem cell homeostasis. Although the signalling cascade of the core Hippo kinases is relatively well understood, little is known about the mechanisms that modulate the activity of the Hippo pathway. Here, we report identification of NEDD4, a HECT-type E3 ubiquitin ligase, as a regulatory component of the Hippo pathway. We demonstrate that NEDD4 ubiquitylates and destabilizes WW45 and LATS kinase, both of which are required for active Hippo signalling. Interestingly, MST1 protects WW45, but not LATS2, against NEDD4. We also provide evidence indicating that NEDD4 inactivation at high cell density is a prerequisite for the elevated Hippo activity linked to contact inhibition. Moreover, NEDD4 promotes intestinal stem cell renewal in Drosophila by suppressing Hippo signalling. Collectively, we present a regulatory mechanism by which NEDD4 controls the Hippo pathway leading to coordinated cell proliferation and apoptosis.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Spinal anesthesia is a safe and widely used procedure. Spinal cord injury is a rare but serious complication from spinal anesthesia occurs, unexpectedly. Risks of direct neural injury from spinal anesthesia increase in tethered cord syndrome that the spinal cord is tethered by the inelastic structure and is, also, extended to the lower lumbar vertebra. A 52-years-old female patient undergoing anti-incontinence surgery developed neurologic symptoms following spinal anesthesia. The low-lying conus (L5 body level) and tethered cord were found during the assessment of neurological symptoms. (Anesth Pain Med 2015; 10: 171-174)

CHFR ubiquitin ligase plays an important role in cell cycle progression and tumorigenesis. CHFR tumor suppressor function is highly associated with its protein level. We recently reported that CHFR protein levels are negatively regulated by SUMOylation-mediated proteasomal degradation. In the present study, we uncover a detailed molecular mechanism how SUMOylation promotes CHFR destabilization. We demonstrate that SUMO modification of CHFR promotes its ubiquitylation and subsequent proteasomal degradation. However, SUMOylation of CHFR does not affect its auto-ubiquitylation, which generally serves as a maintenance mechanism for most ubiquitin ligases. Moreover, the E3 ubiquitin ligase activity of CHFR is dispensable for this SUMOylation-mediated ubiquitylation and degradation. Conversely, SENP2 deSUMOylating enzyme reduces SUMOylation-induced ubiquitylation of CHFR, leading to elevated CHFR protein levels. Taken together, our results present a new regulatory mechanism for CHFR that sequential post-translational modifications of CHFR by SUMO and ubiquitin coordinately regulates its stability.

Background Postoperative nausea and vomiting (PONV) are common complications after anesthesia and surgery. This study was designed to compare the effects of palonosetron and ondansetron in preventing PONV in high-risk patients receiving intravenous opioid-based patient-controlled analgesia (IV-PCA) after gynecological laparoscopic surgery. Methods One hundred non-smoking female patients scheduled for gynecological laparoscopic surgery were randomly assigned into the palonosetron group (n = 50) or the ondansetron group (n = 50). Palonosetron 0.075 mg was injected as a bolus in the palonosetron group. Ondansetron 8 mg was injected as a bolus and 16 mg was added to the IV-PCA in the ondansetron group. The incidences of nausea, vomiting and side effects was recorded at 2 h, 24 h, 48 h and 72 h, postoperatively. Results There were no significant differences between the groups in the incidence of PONV during 72 h after operation. However, the incidence of vomiting was lower in the palonosetron group than in the ondansetron group (18% vs. 4%, P = 0.025). No differences were observed in use of antiemetics and the side effects between the groups. Conclusions The effects of palonosetron and ondansetron in preventing PONV were similar in high-risk patients undergoing gynecological laparoscopic surgery and receiving opioid-based IV-PCA.

The negatively regulating zinc finger protein (NZFP) is an essential transcription repressor required for early development during gastrulation in Xenopus laevis. In this study, we found that NZFP interacts with the small ubiquitin-like modifier (SUMO) conjugation E2 enzyme, Ubc9, and contains three putative SUMO conjugation sites. Studies with NZFP mutants containing mutations at the putative SUMO conjugation sites showed that these sites were able to be modified independently with SUMO. NZFP was found to be localized in the same nuclear bodies with SUMO-1. However, sumoylation of NZFP did not play a role either in the translocation of NZFP into the nucleus or on nuclear body formation. While wild type NZFP showed significant transcriptional repression, SUMO-conjugation site mutants manifested a decrease in transcriptional repression activity which is reversely proportional to the amount of sumoylation. The sumoylation defective mutant lost its TBP binding activity, while wild type NZFP interacted with TBP and inhibited transcription complex formation. These results strongly suggest that the sumoylation of NZFP facilitates NZFP to bind to TBP and the NZFP/TBP complex then represses the transcription of the target gene by inhibiting basal transcription complex formation.

Purpose: This study was to analyzed the types of subjectivity that elderly who live alone caregivers have about the lonely death. Methods: This study objectified the subjective area by applying the Q methodology. It studied 24 caregivers in H region, who responded to 34 Q sample statements. The method of forced distribution was practiced regarding the results on a 9 points Q sample distribution chart. The collected data was analyzed using PC QUANL program. Results: The caregivers' perception of lonely death has been classified into four types: Type 1 ('type of fate-receptive invitation of lonely death'), Type 2 ('type of afterlife-expectantly invitation of lonely death'), Type 3 ('type of death preparation invitation of lonely death'), and type 4 ('type of rejection of lonely death due to attachment with life'). Conclusion: The present study attempts to provide basic resources for the development of nursing-intervention program to solve the problems with lonely death by grasping and understanding the types of the caregivers' perception of lonely death through which it also aims to yield information necessary to improve the quality of life in their remaining years.

CHFR ubiquitin ligase acts as a checkpoint upon DNA damage and its functional inactivation is one of key characteristics of tumor development and metastasis. Despite the crucial role in maintaining genome integrity and cell cycle progression, little is known how CHFR stability is regulated. Here, we showed that CHFR is covalently modified by SUMO-1 at lysine 663 and subsequently destabilized by ubiquitin-proteasome system. While CHFR(K663R) substitution mutation does not alter its subcellular localization, SUMOylation-defective CHFR(K663R)-stable cells exhibit substantial growth suppression due to the increased stability of CHFR(K663R). Moreover, protein level of CHFR, not CHFR(K663R), is rapidly declined under SUMOylation-promoting conditions, and SENP2 deSUMOylating enzyme reverses its SUMO-modification. Collectively, we demonstrated that CHFR stability is regulated by SUMOylation-dependent proteasomal degradation. Therefore, our study underscores the importance of CHFR SUMOylation as a new regulatory mechanism of CHFR and highlights the emerging role of SUMOylation in modulating protein stability.

Subdural hematoma is a serious but rare complication of spinal anesthesia. A 70-year-old woman patient underwent elective total knee replacement under spinal anesthesia. At 4 days postoperatively, the patient complained of headache and vomiting. Brain computed tomography revealed an acute-on-chronic subdural hematoma with midline shift. The patient recovered completely after surgical decompression. We report a patient with an undiagnosed chronic subdural hematoma, who developed acute-on-chronic subdural hematoma after spinal anesthesia.

Background Monitoring of anesthetic depth is important for successful general anesthesia. It is well known that entropy or BIS monitoring assisted titration of anesthetic drugs decreases their consumption. This study evaluated the effect of remifentanil on consumption of sevoflurane during entropy monitored general anesthesia. Methods Patients were randomly assigned to two groups. The R group was administered 0.1 µg/kg/min of remifentanil and inhaled sevoflurane, while the S group was administered only inhaled sevoflurane. Anesthesia was maintained using sevoflurane with nitrous oxide, and entropy was monitored. In both groups, the concentration of sevoflurane was adjusted to keep the state entropy (SE) value between 40 and 60. End-tidal sevoflurane concentration (ET), entropy value, systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were measured at 5 minute intervals, during a 25 minute period after intubation, skin suture and the end of surgery. Results ET was significantly lower in the R group than the S group. There were no significant differences in entropy value between R and S groups. Conclusions Entropy monitored titration of sevoflurane with remifentanil administration decreased ET with stable hemodynamics.

A herniated intervertebral disc is the most common type of soft tissue mass lesion within the lumbar spinal canal. Magnetic resonance imaging (MRI) is a useful tool for the assessment of patients with lower back pain and radiating pain, especially intervertebral disc herniation. MRI findings of intervertebral disc herniation are typical. However, from time to time, despite an apparently classic history and typical MRI findings suggestive of disc herniation, surgical exploration fails to reveal any lesion of an intervertebral disc. Our patient underwent lumbar disc surgery with the preoperative diagnosis of lumbar disc herniation; however, nothing could be found during the surgical procedure, except a swollen nerve root.

CHFR functions as a mitotic checkpoint by delaying entry into metaphase in response to mitotic stress. CHFR is frequently silenced by hypermethylation in human cancers, indicating that CHFR is a tumor suppressor. To further elucidate the role of CHFR in tumorigenesis, we studied the relationship between CHFR and a novel CHFR-interacting protein, HLTF, helicase-like transcription factor. Here we show that CHFR binds to and ubiquitinates HLTF, leading to its degradation. HLTF modulates basal expression of PAI-1 involved in regulation of cell migration. Consistently, overexpression of CHFR inhibits cell migration, resulting from reduced HLTF followed by decreased PAI-1 expression. HLTF expression is also higher in human breast cancer cells where CHFR is not expressed. Taken together, this is the first report identifying the regulatory mechanism of HLTF by CHFR, suggesting that CHFR-mediated downregulation of HLTF may help protect against cancer.

Chest pain is a symptom observed commonly in outpatients and emergency room patients, and its causes are variable. Because treatment and prognosis of chest pain are different depending on its cause, it is more important than anything else to accurately diagnose the cause of chest pain. Most of patients complaining of chest pain undergo basic tests at a private local clinic or at the Internal medicine or chest surgery department of a general hospital and, they are referred to the pain clinic, with a note stating no particular finding. However, if they have sustained severe neuropathic pain in spite of nerve block, accurate diagnosis for chest pain is essential. We experienced rapidly developing spine breakdown and cord compression caused by metastatic spinal tumor in an inpatient who was being treated for chest pain, and thus, we report here in the case with literature review.

Airway management is important during general anesthesia. Difficulties with a direct laryngoscopy can be managed successfully in a routine manner using a laryngeal mask airway. A 65-year-old woman was scheduled to undergo gynecologic surgery. After injecting the intravenous induction agents and muscle relaxants, intubation was attempted with a direct laryngoscope. However, the vocal cords could not be observed with only the epiglottis being slightly visible. Although intubation was re-attempted by another anesthesiologist, it failed. Intubation was successfully performed via an intubating laryngeal mask airway (ILMA) after additional 100% oxygen mask ventilation. We report a case of vocal cord palsy subsequent to tracheal extubation after endotracheal intubation via ILMA.

Placenta accreta is a rare complication of pregnancy with high rates of maternal morbidity and mortality. It is usually discovered when removal of the placenta after delivery is difficult or there is substantial postpartum bleeding. Placenta accreta can be complicated by disseminated intravascular c...

The ubiquitin ligase Chfr polyubiquitylates the histone deacetylase Hdac1, resulting in its proteolysis and the concomitant upregulation of metastasis suppressors, which may provide a molecular explanation for the known effects of Chfr on tumour progression.

Chfr, a checkpoint with FHA and RING finger domains, plays an important role in cell cycle progression and tumor suppression. Chfr possesses the E3 ubiquitin ligase activity and stimulates the formation of polyubiquitin chains by Ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins, including Plk1 and Aurora A. While Chfr is a nuclear protein that functions within the cell nucleus, how Chfr is localized in the nucleus has not been clearly demonstrated. Here, we show that nuclear localization of Chfr is mediated by nuclear localization signal (NLS) sequences. To reveal the signal sequences responsible for nuclear localization, a short lysine-rich stretch (KKK) at amino acid residues 257–259 was replaced with alanine, which completely abolished nuclear localization. Moreover, we show that nuclear localization of Chfr is essential for its checkpoint function but not for its stability. Thus, our results suggest that NLS-mediated nuclear localization of Chfr leads to its accumulation within the nucleus, which may be important in the regulation of Chfr activation and Chfr-mediated cellular processes, including cell cycle progression and tumor suppression.