Role of a mental health physician in the management of oncology patients: a case vignette and the need for collaboration.

There is an interplay between oncology and mental health, resulting in a high prevalence of mental disorders among cancer patients. Out of the several interventions developed to target cancer specifics, collaborative care is indicated due to its efficacy. The perspective delves into the efficacy of collaborative care models, spotlighting a culturally informed strategy designed to harmonize mental and physical health interventions to bolster the overall wellbeing and resilience of individuals battling cancer. Central to our discussion is a compelling case vignette of Raliat, a patient diagnosed with ovarian cancer whose narrative exemplifies the multifaceted challenges cancer patients face, including stigma, psychological distress, and social isolation. Raliat's story illuminates the profound impact of cultural beliefs on patient experiences and the critical importance of a sensitive, holistic approach to care that respects cultural contexts. Through this lens, our analysis reveals that addressing emotional and situational stressors through collaborative care can significantly reduce oxidative stress, potentially decelerating the progression of both cancer and accompanying mental health disorders. We advocate for integrating mental health services into oncological care, drawing on the case vignette to argue for policies that facilitate such merger by employing validated collaborative care models. We conclude with a call for public education to diminish cancer stigma and improve social outcomes, emphasizing the use of a culture-informed PACER (physical, affective, cognitive, environmental, and relationship) strategy in providing comprehensive care for cancer patients and their families.

The association between the Police, Ambulance, Clinician Early Response model and involuntary detentions of people living with mental illness: A retrospective observational study.

WHAT IS KNOWN ON THE SUBJECT?: Involuntary detention is a legislative power that allows people to be taken against their will for a mandatory mental health assessment and is known to be a restrictive and traumatizing process for patients. While there is some literature examining police/ambulance and mental health worker co-response models, the conclusions are mixed as to whether they reduce rates of involuntary detentions in mentally ill people. The Police, Ambulance, Clinician Early Response (PACER) model is an example of a tri-response mental health crisis response team whose role is to respond and assess people thought to be experiencing a mental health crisis. There is little literature to determine whether PACER tri-response model reduces incidents of involuntary detention when compared with standard police and/or ambulance responses. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This paper describes the outcomes of patients assessed by a PACER team, compared with patients who were assessed by police or ambulance. It demonstrates that PACER may reduce unnecessary involuntary detentions through expert mental health assessment for patients coming to emergency services for assistance. It is one of only two published studies examining a tri-response model. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The results of this study may support health and policing policymakers to implement PACER models as a means of reducing involuntary detentions, reducing demand for emergency departments, reducing time spent by emergency services responding to people experiencing mental health crisis and improving outcomes for people with mental illness. ABSTRACT: BACKGROUND: Involuntary detention is a common method of enforcing mental health assessment and treatment; however, it is associated with poor patient outcomes and high emergency service and hospital demand. AIM: To examine the association between (1) Police, Ambulance, Clinician, Early Response (PACER) model, (2) police or (3) ambulance response and rates of involuntary detention of mentally ill people. METHODS: A retrospective observational study using routine administrative data in an Australian City, over a 12-month period (2019-2020). RESULTS: Over a 12-month period, 8577 people received crisis mental health intervention in the study setting. We observed an 18% increase in the relative risk of being involuntarily detained by police, and a 640% increase in the relative risk of being detained by ambulance. The PACER team detained 10% of their total presentations, as compared with 12% by police and 74% by ambulance. Involuntary detentions enacted by PACER were more likely to convert to a post-detention hospitalization (72%), when compared with police (27%) and ambulance (17%). DISCUSSION: PACER was associated with lower rates of involuntary detention and higher rates of post-detention hospitalization when compared to police and ambulance response. IMPLICATIONS FOR PRACTICE: PACER cohort experience more positive outcomes than with police or ambulance cohorts.

Can Pulse Rate Variability be Used to Monitor Compliance with a Breath Pacer?

Slow paced breathing has been demonstrated to provide significant health benefits for a person's health, and, during breathing sessions, it is desirable to monitor that a person is actually compliant with the breath pacer. We explore the potential use of pulse rate variability to monitor compliance with a breath pacer during meditation sessions. The study involved 6 human subjects each participating in 2-3 trials, where they are asked to follow or not to follow the breath pacer, where we collected data on how the magnitude of pulse rate variability changed. Two methods, logistic regression and a running standard deviation technique, were developed to detect non-compliance with the breath pacer based on pulse rate variability metrics. Results indicate that using pulse rate variability alone may not reliably detect non-compliance with the breath pacer. Both models exhibited limitations in terms of false positives and false negatives, with accuracy ranging from 67 to 65%. Existing methods involving visual, audio, and motion signals currently perform better for monitoring compliance with the breath pacer.

The Association between the Police, Ambulance, Clinician Early Response (PACER) Model and Involuntary Detentions of People Living with Mental Illness: A Protocol for a Retrospective Observational Study.

Emergency services are frequently called to attend mental health incidents and are looking for innovative ways to improve their responses and reduce the burden on services. Involuntary detention of people living with mental illness is considered more frequent than necessary, leading to increased pressure on emergency departments, and is often a traumatic experience for patients. The Police, Ambulance, Clinician Early Response (PACER) model was developed in 2019 in Canberra, Australia, and seeks to reduce involuntary detentions by embedding a mental health clinician into emergency services as a mobile mental health crisis response intervention. This protocol details a retrospective cohort study that will examine the association between PACER and involuntary detentions using medical and police records and compare the results to standard ambulance and police responses. We will use relative risk and odds ratio calculations to determine the probability of being involuntarily detained or diverted from hospital; and we will describe the patient characteristics and outcomes in the PACER cohort. Results will be reported using the STROBE checklist for reporting cohort studies. This study was not registered on a publicly accessible registry.

First long-term outcome data for the MicraVR™ transcatheter pacing system: data from the largest prospective German cohort.

AIMS: The MicraVR™ transcatheter pacing system (TPS) has been implemented into clinical routine for several years. The primary recipients are patients in need for VVI pacing due to bradycardia in the setting of atrial fibrillation (AF). Implantation safety and acute success have been proven in controlled studies and registries. So far only few long-term real-life data on TPS exist. We report indication, procedure and outcome data from two high-volume implanting German centers. METHODS: Between 2016 and 2019, 188 (of 303) patients were included. During follow-up (FU), TPS interrogation was performed after 4 weeks and thereafter every 6 months. RESULTS: Indication for TPS implantation in 159/188 (85%) patients was permanent or intermittent AV block III° in the setting of atrial fibrillation. The mean procedure duration was 50 min [35.0-70.0]. The average acute values after system release were: thresholds: 0.5V [0.38-0.74]/0.24ms; R-wave sensing: 10.0mV [8.1-13.5]; impedance: 650 Ohm [550-783]; RV-pacing demand: 16.9% [0.9-75.9]; and battery status: 3.15 V [3.12-3.16]. During FU of 723.4 ± 597.9 days, neither pacemaker failure nor infections were reported. Long-term FU revealed: thresholds: 0.5V [0.38-0.63]/0.24 ms; sensing: 12.3mV [8.9-17.2]; impedance: 570 Ohm [488-633]; RV-pacing demand: 87.1% [29.5-98.6]; and battery status 3.02 V [3.0-3.1]. Forty-three patients died from not-device-related causes. CONCLUSION: This to date largest German long-term dataset for MicraVR™ TPS implantation revealed stable device parameter. Foremost, battery longevity seems to fulfill predicted values despite a significant increase in RV-pacing demand over time and even in patients with consecutive AV-node ablation. Of note, no infections or system failure were observed.

The roles of long non-coding RNAs in the necroptotic signaling of colon cancer cells.

BACKGROUND: Necroptosis is a controlled form of necrosis which can be stimulated in cases where the apoptosis signal is absent. Necroptosis can be induced by DR family ligands and by various intracellular and extracellular stimuli that triggers the activation of DR family ligands. Necrostatins, which are specific RIP1 antagonists, prevent necroptosis by inhibiting RIP1 kinase, allowing survival and propagation of cells in the presence of DR ligands. Furthermore, there is a mounting evidence that long non-coding RNA (lncRNA) molecules accomplish vital functions in cell death processes such as apoptosis, autophagy, pyroptosis, and necroptosis. Accordingly, here we aimed to decipher the lncRNAs that are involved in the control and maintenance of necroptosis signaling. METHODS AND RESULTS: Colon cancer cell lines, HT-29 and HCT-116 were used for the study. For the chemical modulation of necroptosis signaling, 5-Fluorouracil, TNF-α and/or Necrostatin-1 were used. Gene expression levels were determined by quantitative real-time PCR. Remarkably, lncRNA P50-associated COX-2 extragenic RNA (PACER) was identified to be suppressed in necroptosis-induced colon cancers, whereas the expression of PACER was restored when necroptosis was suppressed. In addition, no detectable change was observed in HCT-116 colon cancer cells, as these cells lack the expression of RIP3 kinase. CONCLUSIONS: Collectively, current findings clearly imply that PACER have key regulatory roles in the control of necroptotic cell death signaling circuitry. Notably, the tumor promoter activity of PACER might be responsible for the lack of necroptotic death signal in cancer cells. Also, RIP3 kinase seems to be essential component in PACER-associated necroptosis.

Inflammation-associated long non-coding RNA signature in radicular cyst tissues.

Radicular cysts are characterized by significant levels of changes in inflammatory biomarkers. Among them, interleukins and growth factors have been reported to be deregulated in radicular cyst tissues. Moreover, long non-coding RNAs are recently discovered non-coding RNA molecules that regulate various intracellular stimuli to keep homeostasis in balance. A growing body of evidence suggests that lncRNAs are significantly involved in the regulation of inflammation by targeting various inflammatory biomarkers. Accordingly, the present study was aimed to investigate the gene expression levels of inflammation-related lncRNAs in radicular cysts and show their possible roles in the development of radicular cysts. For the study, a total of 25 patients with a radiologically and pathologically confirmed radicular cyst were enrolled. For the determination of non-coding RNA expression levels, real-time qPCR was used. As a result of the current study, expression levels of PACER and THRIL were found to be significantly elevated in radicular cyst tissues compared to control tissue samples. However, MALAT1, ANRIL, and NEAT1 expression levels were not significantly altered in radicular cyst tissues compared to control tissue samples. In conclusion, long non-coding RNAs, PACER and THRIL, seem to have significant pathophysiological roles by acquiring molecular changes during inflammation and might be involved in the development and formation of radicular cysts.

A gene expression analysis of long non-coding RNAs NKILA and PACER as well as their target genes, NF-κB and cox-2 in bipolar disorder patients.

Bipolar disorder (BD) is a severe condition characterized by periods of mania and depression. Despite advances in the neurobiology of bipolar disorder, the exact etiology of the disease remains unclear. There is evidence that Inflammation is associated with bipolar disorder. COX-2 and NF-κB are two critical mediators in the inflammatory pathways. Long non-coding RNAs (lncRNAs) are a new class of non-coding RNAs that play a wide range of roles, especially in developing and maintaining normal brain functions. Two lncRNAs called PACER and NKILA control the expression of COX-2 and NF-κB genes, respectively. In this study, Expression levels of PACER and NKILA lncRNAs, as well as, COX-2 and NF-κB genes were measured in fifty patients with bipolar disorder and 50 healthy individuals by real-time PCR. Expression levels of NKILA and COX2 were considerably reduced in BD patients compared with healthy controls. Such significant downregulation in the expression of NKILA and PACER was only observed in male patients with BD compared with male healthy subjects. Also, according to the results of the ROC curve, the area under curve values for NKILA and COX2 were 0.68 and 0.52 respectively. Consequently, the NKILA gene could be considered a biomarker. By examining the degree of pairwise correlation between genes, all genes had a significant positive correlation with each other. Taken together, these results revealed a function for NKILA and PACER lncRNAs in the pathogenesis of BD.

How parents assist children's emotion regulation in Turkey: The Turkish adaptation of the parental assistance with child emotion regulation (PACER) questionnaire.

Parents play a critical role in emotional socialization and the development of emotion regulation during childhood. The tools to measure how parents assist children's emotion regulation are very limited. The Parental Assistance with Child Emotion Regulation (PACER) Questionnaire is a novel scale developed for this purpose with excellent psychometric properties. The aim of this study is to adapt the PACER to Turkish and investigate its psychometric properties in the Turkish cultural setting. The data were collected from 700 parents who have children aged birth to 17 years. In addition to the PACER, participants filled out some scales about their own beliefs and behaviors, also their children's psychological symptoms. We confirmed the original ten-factor structures of the PACER in a Turkish sample and the measurement invariance supported the PACER's structure across subgroups. The high internal consistencies of factors were achieved; however, the test-retest reliability was lower than expected. The factors of maladaptive emotion regulation strategies (e.g., rumination, expressive suppression, avoidance) were positively associated with parents' own emotion regulation deficit, symptoms, and child's symptoms, while others (e.g., reappraisal, problem-solving) were negatively associated with them. Overall, our results suggest that the Turkish version of the PACER is a psychometrically valid and reliable measurement to assess how parents support their children to regulate their emotions. We believe that this adaptation allows the scale to be used in developmental and clinical psychology studies and will pave the way for cross-cultural studies.

How Caregivers Support Children's Emotion Regulation: Construct Validation of the Parental Assistance With Child Emotion Regulation (PACER) Questionnaire.

Caregivers play a crucial role in supporting the development of their children's emotion regulation. This study validated the Parental Assistance with Child Emotion Regulation (PACER) Questionnaire in a sample of 491 caregivers (M = 32.89 years) of young children ≤ 5 years. Exploratory structural equation modeling provided evidence of the instrument's ability to assess parental support for 10 distinct emotion regulation strategies that match the intended design of the instrument. Latent profile analysis revealed three distinct caregiver profiles characterized by above-average support for strategies that previously have been shown to be predictive of adaptive outcomes, maladaptive outcomes, or mixed-outcomes, respectively. Results add to existing literature that suggests the PACER is a valid and reliable assessment of caregiver-implemented support of emotion regulation strategies for children ≤ 5 years old. Evidence of distinct caregiver profiles highlights opportunities for prevention and intervention efforts to bolster extrinsic support for adaptive emotion regulation strategies. This instrument may be well-suited to capturing changes throughout the early developmental period, in addition to monitoring caregiver-facing interventions promoting optimal emotion regulation in children.

Longitudinal Association between Weight Status, Aerobic Capacity, Muscular Strength, and Endurance among New York City Youth, 2010-2017.

Background: Child weight status is inversely associated with fitness, but less is known about this relationship across fitness domains. This study examined the longitudinal association between weight status and fitness domains in a large, diverse sample of children. Methods: Data were drawn from the New York City Fitnessgram (2010-2011 to 2017-2018). Height and weight were collected annually and converted to weight status using Centers for Disease Control and Prevention growth charts. Aerobic capacity, muscular strength, and endurance were measured as age and sex standardized z-scores based on the fitness performance tests. Repeated-measures multilevel models were run testing the association between weight status and 1-year lagged fitness domains. Results: The sample included 917,554 children (51.8% male, 39.3% Hispanic, 29.9% non-Hispanic Black, 13.9%, 4.7%, and 1.7% class I, II, and III obesity, respectively). For each fitness domain, fitness scores decreased with increasing weight status across all demographic categories, with the lowest fitness scores observed in children with the most severe obesity, and highest magnitude of effects for aerobic capacity, and particularly among boys, non-Hispanic Whites, and older youth. For example, compared with youth with healthy weight, youth with overweight had 0.28 standard deviation lower aerobic capacity performance [confidence interval (95% CI): -0.29 to -0.28], followed by class 1 obesity (ß = -0.57, 95% CI: -0.58 to -0.57), class 2 obesity (ß = -0.88, 95% CI: -0.88 to -0.88), and class 3 obesity (ß = -1.19, 95% CI: -1.20 to -1.18). Conclusions: Compared with youth with healthy weight, youth at every other weight status had lower subsequent fitness, with the magnitude of the relationship increasing as weight status increased. Future research should examine interventions targeting aerobic capacity to reduce fitness disparities.

Diaphragm pacing using the minimally invasive cervical approach.

CONTEXT: The implantation of commercially available phrenic nerve/diaphragm pacers has been available for more than 40 years and has enabled thousands of patients in over 40 countries to achieve freedom from invasive mechanical ventilation. OBJECTIVE: The cervical approach to implantation of these pacers is described, as are the pros and cons of using this technique compared to intrathoracic and sub-diaphragmatic. METHODS: Study design was a retrospective review of 1,522 subjects from the Avery Biomedical Devices (ABD) database who were implanted with the Avery diaphragm pacer. Long term statistics from patients implanted with diaphragm pacers are presented as well. RESULTS: 17% of cervically placed electrodes required at least one replacement compared to 18% of electrodes placed thoracically. Devices implanted cervically show no significant difference in their longevity than those implanted using the thoracic approach (P value of 0.9382 using Two-Sample t-Test). The mean longevity for both approaches was found to be 6.4 years. The majority of electrodes implanted have never required replacement. A majority of CCHS patients were implanted using the thoracic approach and only find it necessary to use the device during sleeping hours. Most of the cervically implanted patients are found to be older at the time of implantation and implanted for diagnoses that require longer daily use of the device. CONCLUSION: The cervical approach for the implantation of phrenic nerve/diaphragm pacers is the most minimally invasive, but underutilized, technique that allows for the use of local or monitored anesthesia, does not require entering any body cavities, and keeps incision size small.

Evaluation of a tactile breath pacer for sleep problems: A mixed method pilot study.

Sleep problems, like insomnia, are a prevalent condition associated with major health risks. Prevention and treatment of sleep problems are thus essential to preserve physical and mental health. Previous work supports the effectiveness of breathing guidance for sleep problems and recommends breathing exercises as an effective intervention for insomnia. While new technologies can support breathing guidance, such novel devices should be assessed for effectiveness and usability to facilitate implementation and continued use. The current pilot study investigates the acceptability and usability of a mobile tactile breathing device and explores its potential impact on subjective sleep quality. In this mixed-method pilot study, 39 participants tested the breathing device for one month in naturalistic circumstances. We collected their experiences, subjective sleep quality, and feedback regarding the usability of the device and the accompanying app through a survey in a pre-post design. The results show that the breathing device is an acceptable solution for sleep problems and participants particularly appreciate the standalone function and design. Nevertheless, important points of attention, such as the size of the device, were also identified. Explorative analyses suggest that subjective sleep quality improved after using the device and accompanying app. The current study supports the usability and acceptability of a tactile breath pacer and provides preliminary evidence supporting a positive impact of the technology on the sleep quality of participants. Recommendations for developers of breathing technologies and eHealth are devised based on the findings.

Neuronal Rubicon Represses Extracellular APP/Amyloid ß Deposition in Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent age-associated neurodegenerative disease. A decrease in autophagy during aging contributes to brain disorders by accumulating potentially toxic substrates in neurons. Rubicon is a well-established inhibitor of autophagy in all cells. However, Rubicon participates in different pathways depending on cell type, and little information is currently available on neuronal Rubicon's role in the AD context. Here, we investigated the cell-specific expression of Rubicon in postmortem brain samples from AD patients and 5xFAD mice and its impact on amyloid ß burden in vivo and neuroblastoma cells. Further, we assessed Rubicon levels in human-induced pluripotent stem cells (hiPSCs), derived from early-to-moderate AD and in postmortem samples from severe AD patients. We found increased Rubicon levels in AD-hiPSCs and postmortem samples and a notable Rubicon localization in neurons. In AD transgenic mice lacking Rubicon, we observed intensified amyloid ß burden in the hippocampus and decreased Pacer and p62 levels. In APP-expressing neuroblastoma cells, increased APP/amyloid ß secretion in the medium was found when Rubicon was absent, which was not observed in cells depleted of Atg5, essential for autophagy, or Rab27a, required for exosome secretion. Our results propose an uncharacterized role of Rubicon on APP/amyloid ß homeostasis, in which neuronal Rubicon is a repressor of APP/amyloid ß secretion, defining a new way to target AD and other similar diseases therapeutically.

Sharp-nosed Pit Viper (Deinagkistrodon acutus) from Taiwan and China: A comparative study on venom toxicity and neutralization by two specific antivenoms across the Strait.

In East Asia, the Sharp-nosed Pit Viper (Deinagkistrodon acutus) is a medically important venomous snake in Taiwan and China, two geographical areas long separated by the Taiwan Strait. Yet, snake venom variation is little known between specimens found across the Strait. This study thus investigated the intra-species variation of D. acutus venoms from Taiwan (Da-Taiwan) and China (Da-China) in their profiles of gel electrophoresis, toxicity, immunoreactivity and neutralization effect by antivenom. Da-China venom exhibited higher procoagulant, hemorrhagic and lethal activities than Da-Taiwan venom, presumably attributed to the higher abundance of moderate-to-high molecular weight toxins (procoagulants and hemorrhagins) in the venom. The mono-specific antivenoms produced in Taiwan (DaMAV-Taiwan) and China (DaMAV-China) were immunoreactive toward both venoms, and were able to neutralize the venom toxicity to different extents. DaMAV-Taiwan was more efficacious in neutralizing the venom procoagulant and lethal effects, while DaMAV-China was more potent against hemorrhagic effect. The discrepancy in efficacy between the two antivenoms could be due to varying proportions of neutralizing antibodies in the respective products, influenced by techniques of antibody raising and purification. Further study is warranted to elucidate variation in the proteome and antigenicity of D. acutus venom between snakes from Taiwan and China.

The Autophagy Protein Pacer Positively Regulates the Therapeutic Potential of Mesenchymal Stem Cells in a Mouse Model of DSS-Induced Colitis.

Mesenchymal stem cells (MSC) have emerged as a promising tool to treat inflammatory diseases, such as inflammatory bowel disease (IBD), due to their immunoregulatory properties. Frequently, IBD is modeled in mice by using dextran sulfate sodium (DSS)-induced colitis. Recently, the modulation of autophagy in MSC has been suggested as a novel strategy to improve MSC-based immunotherapy. Hence, we investigated a possible role of Pacer, a novel autophagy enhancer, in regulating the immunosuppressive function of MSC in the context of DSS-induced colitis. We found that Pacer is upregulated upon stimulation with the pro-inflammatory cytokine TNFα, the main cytokine released in the inflammatory environment of IBD. By modulating Pacer expression in MSC, we found that Pacer plays an important role in regulating the autophagy pathway in this cell type in response to TNFα stimulation, as well as in regulating the immunosuppressive ability of MSC toward T-cell proliferation. Furthermore, increased expression of Pacer in MSC enhanced their ability to ameliorate the symptoms of DSS-induced colitis in mice. Our results support previous findings that autophagy regulates the therapeutic potential of MSC and suggest that the augmentation of autophagic capacity in MSC by increasing Pacer levels may have therapeutic implications for IBD.

Gastric electric stimulator versus gastrectomy for the treatment of medically refractory gastroparesis.

BACKGROUND: Gastric electrical stimulation (GES) and laparoscopic gastrectomy (LG) are known therapeutic options for medically refractory gastroparesis (MRG) although there are limited data comparing their outcomes. We aim to compare clinical outcomes between patients undergoing GES vs upfront LG for the treatment of MRG while examining factors associated with GES failure and conversion to LG. METHODS: We retrospectively analyzed 181 consecutive patients who underwent GES or LG for MRG at our institution from January 2003 to December 2017. Data collection consisted of chart review and follow-up telephone survey. Statistical analysis utilized Chi-squared, ANOVA, and multivariable logistic regression. RESULTS: Overall, 130 (72%) patients underwent GES and 51 (28%) LG as primary intervention. GES patients were more likely to have diabetic gastroparesis (GES 67% vs LG 39%, p < 0.001), while primary LG patients were more likely to have post-surgical gastroparesis (GES 5% vs LG 43%, p < 0.001). Postoperatively, primary LG patients had higher rates of major in-hospital morbidity events (GES 5% vs LG 18%, p = 0.017) and longer hospital stays (GES 3 vs LG 9 days, p < 0.001). However, over a mean 35-month follow-up period, there were no differences in the rates of major morbidity, readmissions, or mortality. Multivariable regression analysis revealed patients undergoing GES as a primary intervention were less likely to report improvement in symptoms on follow-up compared to primary LG patients OR 0.160 (95% CI 0.048-0.532). Additionally, patients who converted to LG from GES were more likely to have post-surgical gastroparesis as the primary etiology. CONCLUSION: GES as a first-line surgical treatment of MRG was associated with worse outcomes compared to LG. Post-surgical etiology was associated with an increased likelihood of GES failure, and in such patients, upfront gastrectomy may be a superior alternative to GES. Further studies are needed to determine patient selection for operative treatment of MRG.

PACER lncRNA regulates COX-2 expression in lung cancer cells.

Long noncoding RNAs (lncRNAs) are known to regulate gene expression; however, in many cases, the mechanism of this regulation is unknown. One novel lncRNA relevant to inflammation and arachidonic acid (AA) metabolism is the p50-associated COX-2 extragenic RNA (PACER). We focused our research on the regulation of PACER in lung cancer. While the function of PACER is not entirely understood, PACER is known to play a role in inflammation-associated conditions. Our data suggest that PACER is critically involved in COX-2 transcription and dysregulation in lung cancer cells. Our analysis of The Cancer Genome Atlas (TCGA) expression data revealed that PACER expression is significantly higher in lung adenocarcinomas than normal lung tissues. Additionally, we discovered that elevated PACER expression strongly correlates with COX-2 expression in lung adenocarcinoma patients. Specific siRNA-mediated knockdown of PACER decreases COX-2 expression indicating a direct relationship. Additionally, we show that PACER expression is induced upon treatment with proinflammatory cytokines to mimic inflammation. Treatment with prostaglandin E2 (PGE2) induces both PACER and COX-2 expression, suggesting a PGE2-mediated feedback loop. Inhibition of COX-2 with celecoxib decreased PACER expression, confirming this self-regulatory process. Significant overlap between the COX-2 promotor and the PACER promotor led us to investigate their transcriptional regulatory mechanisms. Treatment with pharmacologic inhibitors of NF-κB or AP-1 showed a modest effect on both PACER and COX-2 expression but did not eliminate expression. These data suggest that the regulation of expression of both PACER and COX-2 is complex and intricately linked.

Long Non-Coding RNA PACER Regulates Mycoplasma pneumoniae-induced Inflammatory Response through Interaction with NF-κB.

OBJECTIVE: This study aimed to investigate the role of p50-associated cyclooxygenase- (COX-2) extragenic RNA (PACER) on the inflammation of airway epithelium caused by Mycoplasma pneumoniae (MP) infection. METHODS: A549 cells and MP strain were cultured respectively. The expressions of PACER, IL-8, TNF-α and COX-2 in MP-infected cells were detected by qRT-PCR, the concentration of IL-8 and TNF-α in the supernatant of the cells were detected by ELISA, and the expression of COX-2 protein in the cells was detected by western-blot. After knockdown of PACER, the expression of IL-8, TNF-α and COX-2 in MP infected cells were observed. The activity of NF-κB in cells was detected by fluorescence reporter assay, and the interaction between PACER and NF-κB was verified by RNA immunoprecipitation. RESULTS: First, we observed that PACER was upregulated in MP infected A549 cells. Knockdown of PACER suppressed the production of inflammatory cytokines as well as the expression of COX-2 in A549 cells after MP infection. By performing luciferase reporter assay, we found PACER knockdown inhibited NF-κB activation induced by MP. Furthermore, RNA immunoprecipitation showed that PACER could physically bind to NF-κB p50 in MP-treated A549 cells. CONCLUSION: Collectively, our data demonstrated that attenuation of PACER reduces the inflammatory response of MP-infected epithelial cells via regulating NF-κB.

Minimizing Device-Device Interactions Using Bipolar Pacemaker Leads in a Pediatric Patient.

Phrenic nerve injury can lead to a disruption of the autonomic nervous system (ANS) resulting in episodes of bradycardic arrest. Implanted diaphragmatic pacing has been used to overcome phrenic nerve paralysis, but these do not change the ANS. Therefore, patients with phrenic nerve paralysis may require the implantation of a permanent cardiac pacemaker to overcome bradycardic episodes. Having two electronic devices in the same patient may lead to device-device interaction (DDI). This can result in over-sensing leading to lack of pacing of either device. We present the case of a 17-year-old pediatric male with phrenic nerve injury who required implantation of both diaphragm and cardiac pacemaker. Intra-procedural interrogation of the cardiac pacemaker demonstrated DDI in unipolar mode, but not in bipolar. Thus, we demonstrated the safe utilization of multiple implantable electronic devices in the pediatric patient without device-device interaction.