Fear memory regulation by the cAMP signaling pathway as an index of reexperiencing symptoms in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a psychiatric disorder associated with traumatic memory, yet its etiology remains unclear. Reexperiencing symptoms are specific to PTSD compared to other anxiety-related disorders. Importantly, reexperiencing can be mimicked by retrieval-related events of fear memory in animal models of traumatic memory. Recent studies revealed candidate PTSD-associated genes that were related to the cyclic adenosine monophosphate (cAMP) signaling pathway. Here, we demonstrate the tight linkage between facilitated cAMP signaling and PTSD by analyzing loss- and gain-of-cAMP signaling effects on fear memory in mice and the transcriptomes of fear memory-activated mice and female PTSD patients with reexperiencing symptoms. Pharmacological and optogenetic upregulation or downregulation of cAMP signaling transduction enhanced or impaired, respectively, the retrieval and subsequent maintenance of fear memory in mice. In line with these observations, integrative mouse and human transcriptome analysis revealed the reduced mRNA expression of phosphodiesterase 4B (PDE4B), an enzyme that degrades cAMP, in the peripheral blood of PTSD patients showing more severe reexperiencing symptoms and the mouse hippocampus after fear memory retrieval. Importantly, more severe reexperiencing symptoms and lower PDE4B mRNA levels were correlated with decreased DNA methylation of a locus within PDE4B, suggesting the involvement of methylation in the mechanism of PTSD. These findings raise the possibility that the facilitation of cAMP signaling mediating the downregulation of PDE4B expression enhances traumatic memory, thereby playing a key role in the reexperiencing symptoms of PTSD patients as a functional index of these symptoms.

[Pharmacological Treatment of Trigeminal Neuralgia].

Although carbamazepine is the first-line treatment option for trigeminal neuralgia, it may not be sustained long-term. The benefits of carbamazepine are offset by adverse effects that lead to its withdrawal. The alternatives to carbamazepine include gabapentin, pregabalin, and microgabalin. Although used off-label in Japan, baclofen, lamotrigine, intravenous lidocaine, and botulinum toxin type A are also effective. Clinical experience has shown that alternative treatments are less effective than carbamazepine. Therefore, they can be used instead of or in addition to carbamazepine. The adverse effects of drugs include drowsiness, dizziness, rash, bone marrow suppression, and liver dysfunction. Carbamazepine and lamotrigine are particularly likely to cause severe drug eruptions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Low-dose titration is important to avoid the development of rashes and adverse effects.

Anterior cingulate cortex projections to the dorsal hippocampus positively control the expression of contextual fear generalization.

Fear generalization is one of the main symptoms of posttraumatic stress disorder. In rodents, the anterior cingulate cortex (ACC) and the hippocampus (HPC) control the expression of contextual fear memory generalization. Consistently, ACC projections to the ventral HPC contribute to contextual fear generalization. However, the roles of ACC projections to the dorsal HPC (dHPC) in fear generalization are unclear, although the dHPC is required for the retrieval of recent contextual fear memory. To investigate these roles, we examined the effects of optogenetic silencing and stimulation of these projections in contextual fear generalization at the recent and remote time points. Mice underwent contextual fear conditioning and, at 1 or 28 d later, were tested in the conditioned chamber, a novel context, or a similar context. Optogenetic activation of these projections induced higher freezing in mice in the novel context compared with the control group at a recent (1-d), but not remote (28-d), time point following conditioning, suggesting that activation of this pathway enhances contextual fear generalization. In contrast, optogenetic inactivation of these projections induced lower freezing in the similar context compared with the control group at a recent, but not remote, time point, suggesting that inactivation of this pathway impaired contextual fear generalization. These observations suggest that the ACC to the dHPC projections positively regulate the expression of contextual fear generalization when contextual fear memory is recent.

Applied Improvisation Enhances the Effects of Behavioral Activation on Symptoms of Depression and PTSD in High School Students Affected by the Great East Japan Earthquake.

BACKGROUND: The education system can serve as a community-based resource to support the provision of long-term follow-up care after large-scale disasters. While school-based interventions conducted after a disaster have been confirmed to reduce symptoms of depression and posttraumatic stress disorder (PTSD), adolescents often exhibit low treatment motivation. Traditional methods used to encourage treatment motivation include fun activities, such as applied improv (AIM). This study evaluated the intervention effects and improved motivation of an intervention program combining AIM with the behavioral activation approach (BAA). METHODS: Participants were 253 tenth graders, who were in fifth grade at the time the Great East Japan Earthquake of 2011, and 239 students were included in the analyses. Participants were divided into two groups: the BAA and AIM + BAA groups. Students in each group participated in one class-wide intervention session, which lasted 60 min. Depression, PTSD symptoms, behavioral activation, avoidance, and resilience were evaluated using psychological scales. A participant's evaluations of the intervention were confirmed using the impression sheet consisting of six items that measure comprehension, difficulty, efficacy, generalization, confirmation of a specific situation, and motivation. RESULTS: A two-way analysis of variance (ANOVA) conducted using data from the psychological scale did not reveal a significant effect from the intervention program. However, the Mann-Whitney U-test, which used data from the impression sheet, showed a significant effect on comprehension (p = 0.001), generalization (p = 0.023), and motivation (p = 0.025). CONCLUSION: This study did not confirm the effectiveness of the BAA in reducing symptoms of depression and PTSD in adolescents. Regarding treatment motivation, the AIM + BAA group reported higher motivation than the BAA group. Thus, one session of AIM may contribute to improved treatment motivation in adolescents. AIM creates a safe environment and encourages engagement and participation in interventions. Treatment motivation is an important issue in adolescent therapy, and AIM may help solve this problem.

LOTUS, an endogenous Nogo receptor antagonist, is involved in synapse and memory formation.

The Nogo signal is involved in impairment of memory formation. We previously reported the lateral olfactory tract usher substance (LOTUS) as an endogenous antagonist of the Nogo receptor 1 that mediates the inhibition of axon growth and synapse formation. Moreover, we found that LOTUS plays an essential role in neural circuit formation and nerve regeneration. However, the effects of LOTUS on synapse formation and memory function have not been elucidated. Here, we clearly showed the involvement of LOTUS in synapse formation and memory function. The cultured hippocampal neurons derived from lotus gene knockout (LOTUS-KO) mice exhibited a decrease in synaptic density compared with those from wild-type mice. We also found decrease of dendritic spine formation in the adult hippocampus of LOTUS-KO mice. Finally, we demonstrated that LOTUS deficiency impairs memory formation in the social recognition test and the Morris water maze test, indicating that LOTUS is involved in functions of social and spatial learning and memory. These findings suggest that LOTUS affects synapse formation and memory function.

Discrepancy between CARTO and Rhythmia maps for defining the left atrial low-voltage areas in atrial fibrillation ablation.

Reported mapping procedures of left atrial (LA) low-voltage areas (LVAs) vary widely. This study aimed to compare the PentaRay®/CARTO®3 (PentaRay map) and Orion™/Rhythmia™ (Orion map) systems for LA voltage mapping. This study included 15 patients who underwent successful pulmonary vein isolation (PVI) for atrial fibrillation. After PVI, PentaRay and Orion maps created for all patients were compared. LVAs were defined as sites with ≥ 3 adjacent low-voltage points < 0.5 mV. LVAs were indicated in 8 (53%) among 15 patients, and the average values of the measured LVAs was comparable between the systems (PentaRay map = 5.4 ± 8.7 cm2; Orion map = 4.3 ± 6.4 cm2, p = 0.69). However, in 2 of 8 patients with LVAs, the Orion map indicated LVAs at the septum and posterolateral sites of the LA, respectively, whereas the PentaRay map indicated no LVAs. In those patients, sharp electrograms of > 0.5 mV were properly recorded at the septum and posterolateral sites during appropriate beats in the PentaRay map. The PentaRay map had a shorter procedure time than the Orion map (12 ± 3 min vs. 23 ± 8 min, respectively; p < 0.01). Our study results showed a discrepancy in the LVA evaluation between the PentaRay and Orion maps. In 2 of 15 patients, the Orion map indicated LVAs at the sites where > 0.5-mV electrograms were properly recorded in the PentaRay map.

Hippocampal clock regulates memory retrieval via Dopamine and PKA-induced GluA1 phosphorylation.

Cognitive performance in people varies according to time-of-day, with memory retrieval declining in the late afternoon-early evening. However, functional roles of local brain circadian clocks in memory performance remains unclear. Here, we show that hippocampal clock controlled by the circadian-dependent transcription factor BMAL1 regulates time-of-day retrieval profile. Inducible transgenic dominant negative BMAL1 (dnBMAL1) expression in mouse forebrain or hippocampus disrupted retrieval of hippocampal memories at Zeitgeber Time 8-12, independently of retention delay, encoding time and Zeitgeber entrainment cue. This altered retrieval profile was associated with downregulation of hippocampal Dopamine-cAMP signaling in dnBMAL1 mice. These changes included decreases in Dopamine Receptors (D1-R and D5-R) and GluA1-S845 phosphorylation by PKA. Consistently, pharmacological activation of cAMP-signals or D1/5Rs rescued impaired retrieval in dnBMAL1 mice. Importantly, GluA1 S845A knock-in mice showed similar retrieval deficits with dnBMAL1 mice. Our findings suggest mechanisms underlying regulation of retrieval by hippocampal clock through D1/5R-cAMP-PKA-mediated GluA1 phosphorylation.

Association between treatment-related early changes in psychological factors and development of postherpetic neuralgia.

PURPOSE: To examine the association between catastrophizing and pain intensity with acute herpes zoster, and the association of treatment-related early changes in depressive symptoms, anxiety, and catastrophizing with postherpetic neuralgia (PHN) development, independent of acute pain intensity. METHODS: We analyzed 44 outpatient participants with acute herpes zoster who completed a 6-month follow-up. Participants completed a self-reported questionnaire with a Visual Analog Scale (VAS), the Pain Catastrophizing Scale (PCS), and the Hospital Anxiety and Depression Scale (HADS) at first visit, and 3 and 6 months, thereafter. We assessed associations between acute pain intensity and analyzed factors using univariate regression analyses. Univariate and bivariate logistic regression models were constructed to assess associations of variables at the first visit and early changes in psychological factors with PHN development. RESULTS: Sex, severe skin rash at first visit, PCS, and HADS depression were associated with acute pain intensity {standardized regression coefficient, 0.46 [95% confidence interval (CI) 0.12-0.74], 0.36 (95% CI 0.07-0.65), 0.33 (95% CI 0.03-0.62), 0.47 (95% CI 0.19-0.74), respectively}. Acute pain intensity and early change in pain intensity were associated with PHN development [odds ratio (OR) 1.08 (95% CI 1.02-1.14) OR 2.38 (95% CI 1.10-5.16), respectively]. Decreased PCS was associated with decreased risk of PHN development, independent of acute pain intensity [OR 0.31 (95% CI: 0.12-0.80)]. CONCLUSION: Catastrophizing was associated with acute pain intensity, and lower pain-related catastrophizing among patients with acute herpes zoster was associated with less risk of PHN development, independent of acute pain intensity.

Improvement of PTSD-like behavior by the forgetting effect of hippocampal neurogenesis enhancer memantine in a social defeat stress paradigm.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder associated with memories of traumatic experiences. Recent studies have shown that the forgetting of contextual fear memory is promoted via increased adult hippocampal neurogenesis induced by neurogenesis enhancers, such as memantine (MEM) and exercise, raising the possibility that neurogenesis enhancers improve PTSD by facilitating the forgetting of traumatic memory. On the other hand, repeated exposure to social defeat (SD) stress by aggressor mice induces social avoidance behavior to the aggressor and chronic anxiety-like behavior. In this study, we assumed this SD stress paradigm as a PTSD-like model and examined the effects of treatment with neurogenesis enhancer MEM on SD stress-induced PTSD-like behavior. Male C57BL/6 mice received SD stress for 10 consecutive days and were assessed for social avoidance memory to the aggressor (memory of aggressor mice) and anxiety-like behavior using social interaction and elevated zero maze tasks. Consistent with previous studies, SD mice formed social avoidance memory and exhibited increased anxiety-like behavior. Importantly, subsequent MEM treatment (once a week for 4 weeks) significantly reduced social avoidance behavior, suggesting that MEM-treated SD mice showed forgetting of social avoidance memory. Interestingly, MEM-treated SD mice showed comparable anxiety-like behavior with control mice that were not exposed to SD stress. Moreover, MEM-treated SD mice showed no reinstatement of social avoidance memory following single re-exposure to the aggressor. Our findings suggest that neurogenesis enhancer not only enhanced the forgetting of traumatic memory but also improved PTSD (anxiety)-like behavior.

Dietary heat-killed Lactobacillus brevis SBC8803 (SBL88™) improves hippocampus-dependent memory performance and adult hippocampal neurogenesis.

AIMS: Lactobacillus species are used widely as various food and supplements to improve health. Previous studies have shown that heat-killed Lactobacillus brevis SBC8803 induces serotonin release from intestinal cells and affects sleep rhythm and the autonomic nervous system. However, the effect of SBC8803 on cognitive function remains unknown. Here, we examined the effects of dietary heat-killed SBC8803 on hippocampus-dependent memory and adult hippocampal neurogenesis. METHODS: Hippocampus-dependent memory performance was assessed in mice fed heat-killed SBC8803 using social recognition and contextual fear conditioning tasks. Adult hippocampal neurogenesis was evaluated before, during, and after feeding heat-killed SBC8803 by measuring the number of 5-bromo-2-deoxyuridine (BrdU)-positive cells following systemic injections of BrdU using immunohistochemistry. RESULTS: Mice fed a heat-killed SBC8803 diet showed an improvement of hippocampus-dependent social recognition and contextual fear memories and enhanced adult hippocampal neurogenesis by increasing the survival, but not proliferation, of newborn neurons. CONCLUSION: Dietary heat-killed SBC8803 functions as memory and neurogenesis enhancers.

Motor skills mediated through cerebellothalamic tracts projecting to the central lateral nucleus.

The cerebellum regulates complex animal behaviors, such as motor control and spatial recognition, through communication with many other brain regions. The major targets of the cerebellar projections are the thalamic regions including the ventroanterior nucleus (VA) and ventrolateral nucleus (VL). Another thalamic target is the central lateral nucleus (CL), which receives the innervations mainly from the dentate nucleus (DN) in the cerebellum. Although previous electrophysiological studies suggest the role of the CL as the relay of cerebellar functions, the kinds of behavioral functions mediated by cerebellothalamic tracts projecting to the CL remain unknown. Here, we used immunotoxin (IT) targeting technology combined with a neuron-specific retrograde labeling technique, and selectively eliminated the cerebellothalamic tracts of mice. We confirmed that the number of neurons in the DN was selectively decreased by the IT treatment. These IT-treated mice showed normal overground locomotion with no ataxic behavior. However, elimination of these neurons impaired motor coordination in the rotarod test and forelimb movement in the reaching test. These mice showed intact acquisition and flexible change of spatial information processing in the place discrimination, Morris water maze, and T-maze tests. Although the tract labeling indicated the existence of axonal collaterals of the DN-CL pathway to the rostral part of the VA/VL complex, excitatory lesion of the rostral VA/VL did not show any significant alterations in motor coordination or forelimb reaching, suggesting no requirement of axonal branches connecting to the VL/VA complex for motor skill function. Taken together, our data highlight that the cerebellothalamic tracts projecting to the CL play a key role in the control of motor skills, including motor coordination and forelimb reaching, but not spatial recognition and its flexibility.

TFL1-Like Proteins in Rice Antagonize Rice FT-Like Protein in Inflorescence Development by Competition for Complex Formation with 14-3-3 and FD.

Hd3a, a rice homolog of FLOWERING LOCUS T (FT), is a florigen that induces flowering. Hd3a forms a ternary 'florigen activation complex' (FAC) with 14-3-3 protein and OsFD1 transcription factor, a rice homolog of FD that induces transcription of OsMADS15, a rice homolog of APETALA1 (AP1), which leads to flowering. TERMINAL FLOWER 1 (TFL1) represses flowering and controls inflorescence architecture. However, the molecular basis for floral repression by TFL1 remains poorly understood. Here we show that RICE CENTRORADIALIS (RCN), rice TFL1-like proteins, compete with Hd3a for 14-3-3 binding. All four RCN genes are predominantly expressed in the vasculature, and RCN proteins are transported to the shoot apex to antagonize florigen activity and regulate inflorescence development. The antagonistic function of RCN to Hd3a is dependent on its 14-3-3 binding activity. Our results suggest a molecular basis for regulation of the balance between florigen FT and anti-florigen TFL1.

Investigation of the Correlation between Postherpetic Itch and Neuropathic Pain over Time.

Postherpetic itch (PHI), or herpes zoster itch, is an intractable and poorly understood disease. We targeted 94 herpes zoster patients to investigate their pain and itch intensities at three separate stages of the condition (acute, subacute, and chronic). We used painDETECT questionnaire (PDQ) scores to investigate the correlation between PHI and neuropathic pain. Seventy-six patients were able to complete follow-up surveys. The prevalence of PHI was 47/76 (62%), 28/76 (37%), and 34/76 (45%) at the acute, subacute, and chronic stages, respectively. PHI manifestation times and patterns varied. We investigated the relationship of PHI with neuropathic pain using the visual analog scale (VAS), which is a measure of pain intensity, and the PDQ, which is a questionnaire used to evaluate the elements of neuropathic pain. The VAS and PDQ scores did not differ significantly between PHI-positive and PHI-negative patients. A large neuropathic component was not found for herpes zoster itch, suggesting that neuropathic pain treatments may not able to adequately control the itch. Accordingly, we suggest that a more PHI-focused therapy is required to address this condition.

Distribution of cardiac troponin I in the Japanese general population and factors influencing its concentrations.

BACKGROUND: The 99th percentile of cardiac troponin I level in the general population is accepted as the cut-off for the diagnosis of acute myocardial infarction (AMI). However, it is not clear whether the cut-offs derived in racially and geographically different populations are applicable in Japan. METHODS: Troponin I was determined using the Abbott ARCHITECT STAT high-sensitive troponin I immunoassay in 698 apparently healthy individuals who visited the Japanese Red Cross Medical Center for a health checkup. RESULTS: The 99th percentile of the hsTnI in the overall population was 22.5 (95% confidence interval (CI), 16.8-36.6) pg/mL, 17.7 (95% CI 12.0-22.8) pg/mL for females and 30.6 (95% CI 17.1-53.4) pg/mL for males. The median of the hsTnI in the overall population was 3.2 (95% CI, 3.0-3.3) pg/mL, 2.6 (95% CI 2.4-2.8) pg/mL for females and 4.0 (95% CI 3.8-4.3) pg/mL for males. The age and gender had a significant influence on these values. The troponin I level also showed significant associations with the body mass index (BMI), the gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), estimated glomerular filtration rate (eGFR), and cardiac abnormalities by electrocardiography (ECG) but not with the high-sensitive C-reactive protein (hsCRP) level. CONCLUSIONS: The 99th percentiles of the troponin I measured in the general population in Japan were comparable as the ones derived in the US, Germany, and Singapore. The troponin I level was dependent on the gender, age, BMI, and cardiac abnormalities found by ECG but not by the hsCRP level.

A case of delirium in Tolosa-Hunt syndrome during corticosteroid therapy.

BACKGROUND: Corticosteroid therapy is useful for the resolution of pain and paresis in Tolosa-Hunt syndrome; however, there is no definitive protocol for appropriate dosing, route of administration, or duration of therapy. Steroid psychosis is an adverse reaction to corticosteroid therapy; in severe cases, it can develop into psychiatric disorders such as delirium, depression, and mania. In this case study, we report a patient with Tolosa-Hunt syndrome who developed delirium while receiving corticosteroid therapy. CASE PRESENTATION: The patient was a 70-year-old man being treated for a main complaint of pain in the right eye accompanied by oculomotor paralysis. We suspected Tolosa-Hunt syndrome based on diagnostic imaging and other findings. Steroid pulse therapy was initiated with intravenous methylprednisolone at 1000 mg/day for 3 days, followed by oral prednisolone at 60 mg/day. The pain in the right eye disappeared the day after starting this regimen, and palpebral ptosis also improved. However, 5 days after starting treatment, the patient developed progressively worsening delirium, which was considered an adverse reaction to the steroid pulse therapy. Then, prednisolone treatment was temporarily suspended, and the delirium subsequently disappeared. CONCLUSIONS: The manifestation of steroid psychosis following corticosteroid therapy is dose dependent. Therefore, corticosteroid therapy for elderly patients requires caution and dose modulation because of likely adverse drug reactions.

Drug-induced Pressure Ulcers in a Middle-aged Patient with Early-stage Parkinson's Disease.

Drug-induced pressure ulcer (DIPU), which is a newly recognized adverse drug reaction, is associated with the administration of psychiatric drugs in geriatric patients with dementia. The notification of the causative drugs is crucial to the treatment of DIPU. We herein report the case of a 56-year-old woman with early-stage Parkinson's disease who developed DIPUs after starting olanzapine treatment for depressive symptoms. Our findings illustrate that if an akinetic patient with pressure ulcers is encountered, the patient's medication should be reviewed by a multidisciplinary team, to evaluate whether the development of the pressure ulcer is drug-related, regardless of the patient's age.

Spinal Cord Stimulation Treatment for Persistent Pain After a Burn Injury: A Case Report.

Spinal cord stimulation (SCS) is used to treat neuropathic pain, but there are no published studies on its use to treat burn pain. We used SCS to treat a 67-year-old man suffering from burn pain that could not be managed with high-dose opioids or adjuvant neuropathic analgesics. A trial of SCS markedly reduced the visual analog scale score for pain in the left lateral abdominal and gluteal regions. He underwent permanent implantation of a SCS and achieved an opioid-free state. This case suggests that SCS treatment is a therapeutic option for burn pain refractory to conventional therapy.

Hippocampal neurogenesis enhancers promote forgetting of remote fear memory after hippocampal reactivation by retrieval.

Forgetting of recent fear memory is promoted by treatment with memantine (MEM), which increases hippocampal neurogenesis. The approaches for treatment of post-traumatic stress disorder (PTSD) using rodent models have focused on the extinction and reconsolidation of recent, but not remote, memories. Here we show that, following prolonged re-exposure to the conditioning context, enhancers of hippocampal neurogenesis, including MEM, promote forgetting of remote contextual fear memory. However, these interventions are ineffective following shorter re-exposures. Importantly, we find that long, but not short re-exposures activate gene expression in the hippocampus and induce hippocampus-dependent reconsolidation of remote contextual fear memory. Furthermore, remote memory retrieval becomes hippocampus-dependent after the long-time recall, suggesting that remote fear memory returns to a hippocampus dependent state after the long-time recall, thereby allowing enhanced forgetting by increased hippocampal neurogenesis. Forgetting of traumatic memory may contribute to the development of PTSD treatment.

[Inguinal Approach in Obturator Nerve Block].

The most commonly utilized approaches to obtura- tor nerve block are the pubic approach and the inter- adductor approach. However, the pubic approach is difficult and extremely invasive because a needle must be inserted into the pelvis and there have been some cases of vascular puncture using the pubic approach. Moreover, some cases accompanied clinical signs of local anesthetic toxicity using both approaches. Thus, we devised and performed the inguinal approach, where the femoral artery and vein are shifted outward in the level of the inguinal crease and the needle is inserted vertically from the innerside of them using electric stimulation. However, we experienced some unsuccessful cases due to a single branch block, be- cause the obturator nerve is separated into the ante- rior and posterior branches at the level of the inguinal crease. Choquet reported a new inguinal approach that blocks both branches which is easy and useful because the frequency of the needle insertion is less ; the block performance time is shorter ; the success rate is higher ; and the pain and discomfort are less than that with the pubic approach.

The chimeric transcript RUNX1-GLRX5: a biomarker for good postoperative prognosis in Stage IA non-small-cell lung cancer.

Stage IA non-small-cell lung cancer cases have been recognized as having a low risk of relapse; however, occasionally, relapse may occur. To predict clinical outcome in Stage IA non-small-cell lung cancer patients, we searched for chimeric transcripts that can be used as biomarkers and identified a novel chimeric transcript, RUNX1-GLRX5, comprising RUNX1, a transcription factor, and GLRX5. This chimera was detected in approximately half of the investigated Stage IA non-small-cell lung cancer patients (44/104 cases, 42.3%). Although there was no significant difference in the overall survival rate between RUNX1-GLRX5-positive and -negative cases (P = 0.088), a significantly lower relapse rate was observed in the RUNX1-GLRX5-positive cases (P = 0.039), indicating that this chimera can be used as a biomarker for good prognosis in Stage IA patients. Detection of the RUNX1-GLRX5 chimeric transcript may therefore be useful for the determination of a postoperative treatment plan for Stage IA non-small-cell lung cancer patients.