Hybrid delivery of cluster-set resistance training for individuals previously treated for lung cancer: the results of a single-arm feasibility trial.

BACKGROUND: Individuals with non-small cell lung cancer (NSCLC) are burdened by long-lasting symptoms (e.g., dyspnea and fatigue) post-treatment. These symptoms often reduce physical activity levels and increase the risk of functional decline. Though we have previously proposed cluster-set resistance training to mitigate symptom burden in lung cancer, there is currently no data on the feasibility or acceptability of this mode of exercise in cancer. Therefore, the purpose of this study was to investigate the feasibility and acceptability of a hybrid-delivery home-based cluster-set resistance training program in individuals with NSCLC stages I-III (i.e., early stage). METHODS: This study aimed to recruit individuals with NSCLC stages I-III post-treatment to participate in 8 weeks of home-based resistance training, 3 days per week. The program included supervised sessions in the participants' homes and virtual supervision via videoconferencing. The primary outcome measure of feasibility was evaluated through recruitment, retention, and intervention fidelity (i.e., proportion of exercise completed, relative to what was prescribed). Intervention acceptability (i.e., ease and quality of virtual delivery, level of difficulty, and home-based approach) was assessed using a 4-point Likert-type scale from "strongly disagree" to "strongly agree". RESULTS: Fourteen participants were recruited over a 6-month period, with 11 completing the intervention (2 withdrew due to unrelated illness, 1 withdrew due to requiring active treatment), yielding a retention rate of 79%. Characteristics of the participants who completed the intervention (n = 11) were as follows: mean age: 71 ± 10 years, mean BMI: 29.1 ± 6.5, and average time since diagnosis was 62 ± 51 months. Of completers, 27% were male, and 36% were Black; 10 were stage I (91%), and one was stage II (9%). Mean session attendance was 86.4 ± 9.5%. Mean intervention fidelity was 83.1 ± 13.1%. With regard to acceptability, > 90% of participants positively rated all aspects of the intervention delivery. No adverse events related to exercise were recorded. CONCLUSIONS: The hybrid delivery of a home-based resistance exercise program for individuals previously treated for early-stage NSCLC was found to be safe and feasible. Adaptations to the program for future interventions are required, particularly surrounding resistance exercise programming, and intervention delivery with home visits. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05014035 . Registered January 20, 2021.

Study protocol: investigating the feasibility of a hybrid delivery of home-based cluster set resistance training for individuals previously treated for lung cancer.

BACKGROUND: Symptom burden remains a critical concern for individuals with non-small cell lung cancer (NSCLC) following the completion of treatment. The most common symptom clusters, dyspnea (shortness of breath) and fatigue, can contribute to physical decline, reductions in quality of life, and a higher risk of comorbidities and mortality. Dyspnea is a primary limiter of exercise capacity in individuals with lung cancer, resulting in exercise avoidance and an accelerated physical decline. As such, designing resistance training with cluster sets to mitigate symptoms of dyspnea and fatigue may result in improved exercise tolerance. Thus, maintaining the exercise stimulus via cluster sets, combined with improved tolerance of the exercise, could result in the maintenance of physical function and quality of life. The purpose of this study is to investigate the feasibility and preliminary efficacy of a hybrid-delivery home-based cluster-set resistance training program in individuals with NSCLC. METHODS: Individuals with NSCLC (n = 15), within 12 months of completion of treatment, will be recruited to participate in this single-arm feasibility trial. Participants will complete 8 weeks of home-based resistance training designed to minimize dyspnea and fatigue. The hybrid delivery of the program will include supervised sessions in the participants' home and virtual supervision via video conferencing. The primary outcome of feasibility will be quantified by recruitment rates, retention, acceptability, and intervention fidelity. Exploratory outcomes (dyspnea, fatigue, quality of life, physical function, and body composition) will be assessed pre- and post-intervention. DISCUSSION: This study will provide important data on the feasibility of delivering this intervention and inform procedures for a future randomized controlled trial. TRIAL REGISTRATION: Record not yet public.

Multi-donor × elite-based populations reveal QTL for low-lodging wheat.

KEY MESSAGE: Low-lodging high-yielding wheat germplasm and SNP-tagged novel alleles for lodging were identified in a process that involved selecting donors through functional phenotyping for underlying traits with a designed phenotypic screen, and a crossing strategy involving multiple-donor × elite populations. Lodging is a barrier to achieving high yield in wheat. As part of a study investigating the potential to breed low-lodging high-yielding wheat, populations were developed crossing four low-lodging high-yielding donors selected based on lodging related traits, with three cultivars. Lodging was evaluated in single rows in an early generation and subsequently in plots in 2 years with contrasting lodging environment. A large number of lines lodged less than their recurrent parents, and some were also higher yielding. Heritability for lodging was high, but the genetic correlation between contrasting environments was intermediate-low. Lodging genotypic rankings in single rows did not correlate well with plots. Populations from the highest lodging background were genotyped (90 K iSelect BeadChip array). Fourteen markers on nine chromosomes were associated with lodging, differing under high- versus low-lodging conditions. Of the fourteen markers, ten were found to co-locate with previously identified QTL for lodging-related traits or at homoeologous locations for previously identified lodging-related QTL, while the remaining four markers (in chromosomes 2D, 4D, 7B and 7D) appear to map to novel QTL for lodging. Lines with more favourable markers lodged less, suggesting value in these markers as a selection tool. This study demonstrates that the combination of donor functional phenotyping, screen design and crossing strategy can help identify novel alleles in germplasm without requiring extensive bi-parental populations.

Intravital microscopic observation of the microvasculature during hemodialysis in healthy rats.

Hemodialysis (HD) provides life-saving treatment for kidney failure. Patient mortality is extremely high, with cardiovascular disease (CVD) being the leading cause of death. This results from both a high underlying burden of cardiovascular disease, as well as additional physiological stress from the HD procedure itself. Clinical observations indicate that HD is associated with microvascular dysfunction (MD), underlining the need for a fundamental pathophysiological assessment of the microcirculatory consequences of HD. We therefore successfully developed an experimental small animal model, that allows for a simultaneous real-time assessment of the microvasculature. Using in-house built ultra-low surface area dialyzers and miniaturized extracorporeal circuit, we successfully dialyzed male Wistar Kyoto rats and combined this with a simultaneous intravital microscopic observation of the EDL microvasculature. Our results show that even in healthy animals, a euvolemic HD procedure can induce a significant systemic hemodynamic disturbance and induce disruption of microvascular perfusion (as evidence by a reduction in the proportion of the observed microcirculation receiving blood flow). This study, using a new small animal hemodialysis model, has allowed direct demonstration that microvascular blood flow in tissue in skeletal muscle is acutely reduced during HD, potentially in concert with other microvascular beds. It shows that preclinical small animal models can be used to further investigate HD-induced ischemic organ injury and allow rapid throughput of putative interventions directed at reducing HD-induced multi-organ ischemic injury.

Does instillation of lidocaine gel following flexible cystoscopy decrease the severity of post procedure symptoms? A randomised controlled trial assessing the efficacy of lidocaine gel post flexible cystoscopy.

OBJECTIVE: To assess whether instillation of lidocaine gel both before and after flexible cystoscopy is more effective at reducing post procedural symptoms than instillation of lidocaine gel pre flexible cystoscopy alone. We hypothesise that inadequate urethral dwell time and dilution of lidocaine gel by the irrigation fluid during flexible cystoscopy limits its anaesthetic efficacy. Only one other study has attempted to reduce bothersome urinary symptoms through an intervention after flexible cystoscopy. METHODS: This was a randomised controlled trial in which patients were randomised 1:1 to receive lidocaine gel pre and post flexible cystoscopy (treatment) or lidocaine gel pre flexible cystoscopy only (control). Patient-reported outcome measures were used to assess symptoms and quality of life prior to cystoscopy, on day 2 and day 7 post cystoscopy. RESULT: Fifty patients were divided equally between the treatment and control groups. There were no significant differences in baseline characteristics between the groups (p = 1.000). An overall symptoms variable was measured, though no significant difference was found in the distribution of responses between the groups at baseline, 2 or 7 days after the flexible cystoscopy (p = 0.423, 0.651,0.735). In the treatment group, 1 patient (4.0%) presented to a doctor for review following flexible cystoscopy, and 4 patients (16.0%) presented in the control group (p = 0.349). CONCLUSION: Initial study results suggest that post-operative lidocaine does not significantly limit the exacerbation of urinary symptoms following flexible cystoscopy; however, our results are not powered to detect a small difference. We do not recommend a change in practice based on our results.

Obstructive Sleep Apnea in Obese Patients: a UK Population Analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is an increasingly common disorder associated with increased cardiovascular disease, mortality, reduced productivity, and an increased risk of road traffic accidents. A significant proportion of patients with OSA in the UK are undiagnosed. This study aims to identify risk factors for OSA in an obese cohort. METHOD: A population-based study was conducted of obese patients (BMI ≥ 30 kg/m2) from the Clinical Practice Research Datalink (CPRD). A logistic regression model was used to calculate odds ratios (ORs) for developing OSA according to other clinicopathological characteristics. Multivariate analysis was conducted of individual factors that affect the propensity to develop OSA. Statistical significance was defined as p < 0.050. RESULTS: From 276,600 obese patients identified during a data extraction of the CPRD in July 2017, the prevalence of OSA was 5.4%. The following risk factors were found to be independently associated with increased likelihood of OSA: male sex (OR = 3.273; p < 0.001), BMI class II (OR = 1.640; p < 0.001), BMI class III (OR = 3.768; p < 0.001), smoking (OR = 1.179; p < 0.001), COPD (OR = 1.722; p < 0.001), GERD (OR = 1.557; p < 0.001), hypothyroidism (OR = 1.311; p < 0.001), acromegaly (OR = 3.543; p < 0.001), and benzodiazepine use (OR = 1.492; p < 0.001). Bariatric surgery was associated with reduced risk of OSA amongst this obese population (OR = 0.260; p < 0.001). CONCLUSIONS: In obese patients, there are numerous comorbidities that are associated with increased likelihood of OSA. These factors can help prompt clinicians to identify undiagnosed OSA. Bariatric surgery appears to be protective against developing OSA.

Articulating the effect of food systems innovation on the Sustainable Development Goals.

Food system innovations will be instrumental to achieving multiple Sustainable Development Goals (SDGs). However, major innovation breakthroughs can trigger profound and disruptive changes, leading to simultaneous and interlinked reconfigurations of multiple parts of the global food system. The emergence of new technologies or social solutions, therefore, have very different impact profiles, with favourable consequences for some SDGs and unintended adverse side-effects for others. Stand-alone innovations seldom achieve positive outcomes over multiple sustainability dimensions. Instead, they should be embedded as part of systemic changes that facilitate the implementation of the SDGs. Emerging trade-offs need to be intentionally addressed to achieve true sustainability, particularly those involving social aspects like inequality in its many forms, social justice, and strong institutions, which remain challenging. Trade-offs with undesirable consequences are manageable through the development of well planned transition pathways, careful monitoring of key indicators, and through the implementation of transparent science targets at the local level.

Hemodynamic response to non-pneumatic anti-shock compression garments in patients with renal dysfunction.

BACKGROUND: Patients with chronic kidney disease are at higher risk of developing cardiovascular disease. Chronic exposure to intermittent hemodialysis may be a source of added stress to the cardiovascular system; intradialytic hypotension is a common complication of hemodialysis, and repeated events may lead to hemodynamic stress and ischemic injuries. Administration of non-pneumatic compression stockings to the lower limbs has demonstrated hemodynamic stabilizing effects in other settings and may provide similar benefits in the kidney disease population. Therefore, we conducted this pilot study assessing the feasibility and tolerability of the application of non-pneumatic compression stockings to patients with kidney disease. We also assessed the changes in hemodynamic measurements following the application of the compression stockings to explore the biological feasibility of this being an effective intervention for intradialytic hypotension. METHODS: Fifteen individuals were enrolled in the study (5 healthy, 5 chronic kidney disease patients, and 5 dialysis patients). Outcomes including hemodynamic parameters such as cardiac output, peripheral vascular resistance, and blood pressure were measured using continuous pulse wave analysis. Changes in global longitudinal strain were measured via echocardiography. These outcome measurements were made before and after the application of compression stockings. RESULTS: All study participants tolerated the compression garments well and without complication. Hemodynamic response to lower body compression caused varying effects on cardiac output, mean arterial pressure and global longitudinal strain. Some individuals saw large improvements in hemodynamic parameters while in others the opposite effect was observed. No consistent response was elicited. CONCLUSIONS: Application of compression stockings to patients with renal dysfunction is well-tolerated. However, significant variations in hemodynamic outcomes exist, and may be a barrier for larger scale trials without prior identification of specific patient characteristics indicating likely benefit from the application of external compression. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02915627, Registration Date: Sept 27, 2016.

A preliminary assessment of mercury in the feathers of migratory songbirds breeding in the North American subarctic.

Passerines appear to have a greater sensitivity to mercury than other avian orders, and little data exists for mercury exposure in songbirds breeding at high latitudes. In this preliminary study, we examined mercury exposure in 12 migratory songbird species breeding in Denali National Park & Preserve, in subarctic interior Alaska. Overall, we analyzed 343 feather samples collected in 2015-2017 for their total mercury content. Mercury levels found in feathers indicates exposure during the period of feather growth, which we assume largely took place on the breeding ground. In this limited sample of songbird feathers, mercury concentrations ranged from near zero to 6.34 µg/g. Most species sampled showed relatively low mercury, but some individuals had high enough concentrations to be subject to adverse physiological and behavioral effects. There was an indication that mercury concentrations of breeding songbirds may vary by diet composition, with non-invertivorous species possibly tending towards lower mercury concentrations. Overall, however, the degree of mercury exposure observed was low for songbirds breeding in the subarctic. Further examination would prove useful in clarifying mercury exposure and ecological relationships in this under-studied region.

Genetic control of some plant growth characteristics of bread wheat (Triticum aestivum L.) under aluminum stress.

BACKGROUND: Biomass yield is an important trait for wheat breeding programs. Enhancing the yield of the aerial components of wheat cultivars will be an integral part of future wheat improvement. Aluminum (Al) toxicity is one of the main factors limiting wheat growth and production in acid soils, which occur on up to 50% of the arable lands of the world especially in tropical and subtropical regions. OBJECTIVE: Our objective was to identify quantitative trait loci (QTL) of plant growth characteristics and yield in wheat. METHODS: A recombinant inbred line (RIL) population consisting of 167 lines, derived from a cross between SeriM82 and Babax were evaluated under two Al treatments (+ Al, 800 µM of Al; -Al, 0 µM of Al) in the field based on an alpha lattice design with two replications for two consecutive crop seasons. RESULTS: A total of 40 QTLs including nine putative and 31 suggestive QTLs were found for all traits using the composite interval mapping (CIM) method. By mixed model-based composite interval mapping (MCIM) method, 42 additive QTLs and nine pairs of epistatic effects were detected for studied traits, of which 20 additive and six pairs of epistatic QTLs showed significant QTL × environment interactions. Most of the detected QTLs across environments were stable, and the highest number of stable QTLs was related to A genome. Co-localization of QTL was found on linkage groups (LGs) 2B, 4B, 6A-a, and 7A (CIM method) and 2A-d, and 6A-a (MCIM method). CONCLUSION: These results have implications for selection strategies in biomass yield and for increasing the yield of the aerial part of wheat following further evaluations in various genetic backgrounds and environments.

Does fluoroscopy prevent inadvertent parathyroidectomy in thyroid surgery?

INTRODUCTION: Near-infrared imaging may facilitate intraoperative identification of parathyroid glands by causing autofluorescence but its clinical value has not been established. Inadvertent parathyroidectomy occurs in 5-22% of thyroidectomies and is associated with temporary and permanent hypoparathyroidism. The aim of this study was to determine whether near-infrared imaging prevents inadvertent parathyroidectomy and early hypocalcaemia as a surrogate for permanent hypoparathyroidism. MATERIALS AND METHODS: Near-infrared imaging was used in a prospective cohort of consecutive thyroidectomies. Thyroidectomies performed prior to the introduction of near-infrared imaging formed a control group. The thyroid bed and specimen were scanned with near-infrared imaging. Areas of autofluorescence on the specimen were examined and any parathyroid tissue found was autotransplanted. Inadvertent parathyroidectomy was therefore recorded as established intraoperatively by near-infrared imaging (allowing autotransplantation) or on subsequent histology (missed). Serum calcium and parathyroid hormone were measured on day one and at two weeks and six months postoperatively. RESULTS: A total of 269 patients were included: 106 near-infrared imaging and 163 controls. Inadvertent parathyroidectomy was detected by near-infrared imaging in two (and autotransplantation performed) and histologically (i.e. missed by near-infrared imaging in 13, 12.3% vs 17, 10.4% controls). Neither result was statistically significant (P = 0.08, 0.89). There was no significant difference in serum calcium or parathyroid hormone between near-infrared imaging and control groups at one day, two weeks or thereafter. DISCUSSION: Near-infrared imaging may detect inadvertent parathyroidectomy and may allow autotransplantation. It did not, however, reduce the incidence of missed inadvertent parathyroidectomy and no difference was seen in early hypocalcaemia or late hypoparathyroidism. Current near-infrared imaging technology does not appear to confer a clinical benefit sufficient to justify its use.

A critical review of thyroidectomy consent in the UK.

BACKGROUND: In 2015-16, the National Health Service (NHS) Litigation Authority received 10,965 claims for clinical negligence, with surgery having the highest number of claims. Currently a sum amounting to 25% of the annual NHS budget has been ring-fenced to meet extant claims. Claims made on a basis of inadequate informed consent are increasingly seen with many achieving a successful plaintiff outcome. There are presently no UK guidelines for thyroidectomy consent. METHOD: A prospective study was performed to investigate current consent practice among the British Association of Endocrine and Thyroid Surgeons (BAETS) membership and patients having previously undergone thyroidectomy. For surgeons, the Bolam legal test applied where surgeons declared what risks and complications they routinely consented for during their practice. A study was also undertaken in patients who had previously undergone thyroidectomy for cancer applying the rule of Montgomery. RESULTS: Consent practice from 193 surgeons and data from 415 patients was analysed. In total thyroidectomy for cancer, 95% of surgeons consent for Recurrent Laryngeal Nerve (RLN) injury and temporary or permanent voice change. 70% specifically consent for External Laryngeal Nerve (ELN) injury, 50% for tracheostomy and 55% for general anaesthetic associated complications. Analysis of patient data showed they would like to be consented for far more risks than they are presently informed about in general medical practice. There was significant variation in the consenting practice in BAETS surgeons. CONCLUSION: A BAETS approved consensus guideline to standardise UK consent practice would be appropriate. This may reduce complaints, litigation claims and guide expert witnesses.

Temperature and moisture are minor drivers of regional-scale soil organic carbon dynamics.

Storing large amounts of organic carbon, soils are a key but uncertain component of the global carbon cycle, and accordingly, of Earth System Models (ESMs). Soil organic carbon (SOC) dynamics are regulated by a complex interplay of drivers. Climate, generally represented by temperature and moisture, is regarded as one of the fundamental controls. Here, we use 54 forest sites in Switzerland, systematically selected to span near-independent gradients in temperature and moisture, to disentangle the effects of climate, soil properties, and landform on SOC dynamics. We estimated two SOC turnover times, based on bulk soil 14C measurements (τ14C) and on a 6-month laboratory soil incubation (τi). In addition, upon incubation, we measured the 14C signature of the CO2 evolved and quantified the cumulated production of dissolved organic carbon (DOC). Our results demonstrate that τi and τ14C capture the dynamics of contrasting fractions of the SOC continuum. The 14C-based τ14C primarily reflects the dynamics of an older, stabilised pool, whereas the incubation-based τi mainly captures fresh readily available SOC. Mean site temperature did not raise as a critical driver of SOC dynamics, and site moisture was only significant for τi. However, soil pH emerged as a key control of both turnover times. The production of DOC was independent of τi and not driven by climate, but primarily by the content of clay and, secondarily by the slope of the site. At the regional scale, soil physicochemical properties and landform appear to override the effect of climate on SOC dynamics.

Overexpression of a predominantly root-expressed NAC transcription factor in wheat roots enhances root length, biomass and drought tolerance.

KEY MESSAGE: TaRNAC1 is a constitutively and predominantly root-expressed NAC transcription factor. TaRNAC1 overexpression in wheat roots confers increased root length, biomass and drought tolerance and improved grain yield under water limitation. A large and deep root system is an important trait for yield sustainability of dryland cereal crops in drought-prone environments. This study investigated the role of a predominantly root-expressed NAC transcription factor from wheat (TaRNAC1) in the root growth. Expression analysis showed that TaRNAC1 was a constitutively expressed gene with high level expression in the roots and was not drought-upregulated. Overexpression of TaRNAC1 in wheat using a predominantly root-expressed promoter resulted in increased root length and biomass observed at the early growth stage and a marked increase in the maturity root biomass with dry root weight of > 70% higher than that of the wild type plants. Analysis of some root growth-related genes revealed that the expression level of GA3-ox2, which encodes GIBBERELLIN 3-OXIDASE catalysing the conversion of inactive gibberellin (GA) to active GA, was elevated in the roots of transgenic wheat. TaRNAC1 overexpressing transgenic wheat showed more dehydration tolerance under polyethylene glycol (PEG) treatment and produced more aboveground biomass and grain under water-limited conditions than the wild type plants. These data suggest that TaRNAC1 may play a role in root growth and be used as a molecular tool for potential enlargement of root system in wheat.

The feasibility of a pragmatic distance-based intervention to increase physical activity in lung cancer survivors.

The purpose of this study was to investigate the feasibility and preliminary efficacy of a pragmatic distance-based intervention designed to increase physical activity (PA) participation in lung cancer survivors. Fourteen lung cancer survivors were recruited via invitation from the State Cancer Registry to join a 12-week PA intervention of print materials paired with brief telephone follow-up. Outcome measures of feasibility, PA participation and quality of life (QoL) were assessed at baseline, post-intervention and follow-up via telephone interview. Eligibility, recruitment and attrition rates were 16%, 58% and 29% respectively. No adverse events were reported; however, pain scores worsened following the intervention (median change -3.6, IQR -8.0, 0.0). Average intervention adherence was 91% with low median ratings of participation burden (i.e., all items 1/7) and high trial evaluation (i.e., all items 7/7). Post-intervention, median change in self-reported moderate and vigorous PA was 84 min (IQR -22, 188), and several domains of QoL improved. However, for both of these outcomes, improvements were not maintained at follow-up. Our findings suggest that this pragmatic distance-based intervention was safe, had good adherence rates, and indicate potential for improving short-term PA and QoL in lung cancer survivors. Additional strategies are needed to improve other indicators of feasibility, particularly recruitment, retention and long-term maintenance of improvements. Australian New Zealand Clinical Trials Registration: ACTRN12612000085875.

A connectomic approach for subcallosal cingulate deep brain stimulation surgery: prospective targeting in treatment-resistant depression.

Target identification and contact selection are known contributors to variability in efficacy across different clinical indications of deep brain stimulation surgery. A retrospective analysis of responders to subcallosal cingulate deep brain stimulation (SCC DBS) for depression demonstrated the common impact of the electrical stimulation on a stereotypic connectome of converging white matter bundles (forceps minor, uncinate fasciculus, cingulum and fronto-striatal fibers). To test the utility of a prospective connectomic approach for SCC DBS surgery, this pilot study used the four-bundle tractography 'connectome blueprint' to plan surgical targeting in 11 participants with treatment-resistant depression. Before surgery, targets were selected individually using deterministic tractography. Selection of contacts for chronic stimulation was made by matching the post-operative probabilistic tractography map to the pre-surgical deterministic tractography map for each subject. Intraoperative behavioral responses were used as a secondary verification of location. A probabilistic tract map of all participants demonstrated inclusion of the four bundles as intended, matching the connectome blueprint previously defined. Eight of 11 patients (72.7%) were responders and 5 were remitters after 6 months of open-label stimulation. At one year, 9 of 11 patients (81.8%) were responders, with 6 of them in remission. These results support the utility of a group probabilistic tractography map as a connectome blueprint for individualized, patient-specific, deterministic tractography targeting, confirming retrospective findings previously published. This new method represents a connectomic approach to guide future SCC DBS studies.

Effects of vagus nerve stimulation on extinction of conditioned fear and post-traumatic stress disorder symptoms in rats.

Exposure-based therapies help patients with post-traumatic stress disorder (PTSD) to extinguish conditioned fear of trauma reminders. However, controlled laboratory studies indicate that PTSD patients do not extinguish conditioned fear as well as healthy controls, and exposure therapy has high failure and dropout rates. The present study examined whether vagus nerve stimulation (VNS) augments extinction of conditioned fear and attenuates PTSD-like symptoms in an animal model of PTSD. To model PTSD, rats were subjected to a single prolonged stress (SPS) protocol, which consisted of restraint, forced swim, loss of consciousness, and 1 week of social isolation. Like PTSD patients, rats subjected to SPS show impaired extinction of conditioned fear. The SPS procedure was followed, 1 week later, by auditory fear conditioning (AFC) and extinction. VNS or sham stimulation was administered during half of the extinction days, and was paired with presentations of the conditioned stimulus. One week after completion of extinction training, rats were given a battery of behavioral tests to assess anxiety, arousal and avoidance. Results indicated that rats given SPS 1 week prior to AFC (PTSD model) failed to extinguish the freezing response after eleven consecutive days of extinction. Administration of VNS reversed the extinction impairment and attenuated reinstatement of the conditioned fear response. Delivery of VNS during extinction also eliminated the PTSD-like symptoms, such as anxiety, hyperarousal and social avoidance for more than 1 week after VNS treatment. These results provide evidence that extinction paired with VNS treatment can lead to remission of fear and improvements in PTSD-like symptoms. Taken together, these findings suggest that VNS may be an effective adjunct to exposure therapy for the treatment of PTSD.