The LTAR cropland common experiment in the Lower Mississippi River Basin.

The Lower Mississippi River Basin-Long-Term Agroecosystem Research Site (LMRB-LTAR) encompasses six states from Missouri to the Gulf of Mexico and is coordinated by the USDA-ARS National Sedimentation Laboratory, Oxford, MS. The overarching goal of LTAR is to assess regionally diverse and geographically scalable farming practices for enhanced sustainability of agroecosystem goods and services under changing environment and resource-use conditions. The LMRB-LTAR overall goal is to assess sustainable row crop agricultural production systems that integrate regional environmental and socioeconomic needs. Primary row crops in the region include soybeans, corn, cotton, rice, and sugarcane with crop rotations influenced by commodity crop price and other factors. The field-scale common experiment (CE) includes four row crop farms (26-101 ha) established in 2021 and 2023. Three fields are managed with alternative practices, including reduced tillage, cover crops, and automated prescription irrigation, and three fields are managed with prevailing farming practices, consisting of conventional tillage, no cover crop, and nonprescription irrigation. Treatment effects on crop productivity, soil quality, water use efficiency, water quality, and carbon storage are assessed. Research from the LMRB CE will deliver outcomes linked to overarching LTAR network goals, including innovative agricultural systems, strengthened partnerships, data management technologies, and precision environmental tools.

Epigenetic Priming by Hypomethylation Enhances the Immunogenic Potential of Tolinapant in T-cell Lymphoma.

Programmed cell death mechanisms are important for the regulation of tumor development and progression. Evasion of and resistance to apoptosis are significant factors in tumorigenesis and drug resistance. Bypassing apoptotic pathways and eliciting another form of regulated cell death, namely necroptosis, an immunogenic cell death (ICD), may override apoptotic resistance. Here, we present the mechanistic rationale for combining tolinapant, an antagonist of the inhibitor of apoptosis proteins (IAP), with decitabine, a hypomethylating agent (HMA), in T-cell lymphoma (TCL). Tolinapant treatment alone of TCL cells in vitro and in syngeneic in vivo models demonstrated that ICD markers can be upregulated, and we have shown that epigenetic priming with decitabine further enhances this effect. The clinical relevance of ICD markers was confirmed by the direct measurement of plasma proteins from patients with peripheral TCL treated with tolinapant. We showed increased levels of necroptosis in TCL lines, along with the expression of cancer-specific antigens (such as cancer testis antigens) and increases in genes involved in IFN signaling induced by HMA treatment, together deliver a strong adaptive immune response to the tumor. These results highlight the potential of a decitabine and tolinapant combination for TCL and could lead to clinical evaluation. SIGNIFICANCE: The IAP antagonist tolinapant can induce necroptosis, a key immune-activating event, in TCL. Combination with DNA hypomethylation enhances tolinapant sensitivity and primes resistant cells by re-expressing necrosome proteins. In addition, this combination leads to increases in genes involved in IFN signaling and neoantigen expression, providing further molecular rationale for this novel therapeutic option.

Predictive Dosimetry and Outcomes of Hepatocellular Carcinoma Treated by Yttrium-90 Resin Microsphere Radioembolization: A Retrospective Analysis Using Technetium-99m Macroaggregated Albumin SPECT/CT and Planning Software.

PURPOSE: To characterize estimated mean absorbed tumor dose (ADT), objective response (OR), and estimated target dose of hepatocellular carcinoma (HCC) after resin microsphere yttrium-90 (90Y) radioembolization using partition dosimetry. MATERIALS AND METHODS: In this retrospective, single-center study, multicompartment dosimetry of index tumors receiving 90Y radioembolization between October 2015 and June 2022 was performed using a commercial software package and pretreatment technetium-99m macroaggregated albumin single photon emission computed tomography (SPECT)/computed tomography (CT). In total, 101 patients with HCC underwent 102 treatments of 127 index tumors. Patients underwent imaging every 2-3 months after treatment to determine best response per modified Response Evaluation Criteria in Solid Tumors (mRECIST). Best response was defined as the greatest response category per mRECIST and categorized as OR or nonresponse (NR). A Cox proportional hazards model evaluated the probability of tumor OR and progression-free survival using ADT. RESULTS: The median follow-up period was 148 days (interquartile range [IQR], 92-273 days). The median ADT of OR was 141.9 Gy (IQR, 89.4-215.8 Gy) compared with the median ADT of NR treatments of 70.8 Gy (IQR, 42.0-135.3 Gy; P < .001). Only ADT was predictive of response (hazard ratio = 2.79 [95% confidence interval {CI}: 1.44-5.40]; P = .003). At 6 months, an ADT of 157 Gy predicted 90.0% (95% CI: 41.3%-98.3%) probability of OR. At 1 year, an ADT of 157 Gy predicted 91.6% (95% CI: 78.3%-100%) probability of progression-free survival. Partition modeling and delivered activity were predictive of progression (P = .021 and P = .003, respectively). CONCLUSIONS: For HCC treated with resin microspheres, tumors receiving higher ADT exhibited higher rates of OR. An ADT of 157 Gy predicted 90.0% OR at 6 months.

Prolonged Gastrointestinal Manifestations After Recovery From COVID-19.

BACKGROUND & AIMS: Acute enteric infections are well known to result in long-term gastrointestinal (GI) disorders. Although COVID-19 is principally a respiratory illness, it demonstrates significant GI tropism, possibly predisposing to prolonged gut manifestations. We aimed to examine the long-term GI impact of hospitalization with COVID-19. METHODS: Nested within a large-scale observational cohort study of patients hospitalized with COVID-19 across North America, we performed a follow-up survey of 530 survivors 12-18 months later to assess for persistent GI symptoms and their severity, and for the development of disorders of gut-brain interaction (DGBIs). Eligible patients were identified at the study site level and surveyed electronically. The survey instrument included the Rome IV Diagnostic Questionnaire for DGBI, a rating scale of 24 COVID-related symptoms, the Gastrointestinal Symptoms Rating Scale, and the Impact of Events-Revised trauma symptom questionnaire (a measure of posttraumatic stress associated with the illness experience). A regression analysis was performed to explore the factors associated with GI symptom severity at follow-up. RESULTS: Of the 530 invited patients, 116 responded (52.6% females; mean age, 55.2 years), and 73 of those (60.3%) met criteria for 1 or more Rome IV DGBI at follow-up, higher than the prevalence in the US general population (P < .0001). Among patients who experienced COVID-related GI symptoms during the index hospitalization (abdominal pain, nausea, vomiting, or diarrhea), 42.1% retained at least 1 of these symptoms at follow-up; in comparison, 89.8% of respondents retained any (GI or non-GI) COVID-related symptom. The number of moderate or severe GI symptoms experienced during the initial COVID-19 illness by self-report correlated with the development of DGBI and severity of GI symptoms at follow-up. Posttraumatic stress disorder (Impact of Events-Revised score ≥33) related to the COVID-19 illness experience was identified in 41.4% of respondents and those individuals had higher DGBI prevalence and GI symptom severity. Regression analysis revealed that higher psychological trauma score (Impact of Events-Revised) was the strongest predictor of GI symptom severity at follow-up. CONCLUSIONS: In this follow-up survey of patients 12-18 months after hospitalization with COVID-19, there was a high prevalence of DGBIs and persistent GI symptoms. Prolonged GI manifestations were associated with the severity of GI symptoms during hospitalization and with the degree of psychological trauma related to the illness experience.

Partition Dosimetry and Outcomes of Metastatic Neuroendocrine Tumors after Yttrium-90 Resin Microsphere Radioembolization.

PURPOSE: To characterize estimated mean tumor-absorbed dose (ADT) and objective response of metastatic neuroendocrine tumor (NET) after resin microsphere yttrium-90 (90Y) hepatic radioembolization using partition dosimetry. MATERIALS AND METHODS: In this retrospective, single-center study, multicompartment dosimetry of index tumors receiving 90Y radioembolization between 2013 and 2022 involved the use of Sureplan (MIM Software, Cleveland, Ohio) and technetium-99m macroaggregated albumin single photon emission computed tomography (SPECT) combined with computed tomography. Thirty-six patients with NET underwent treatment of 56 index tumors. Patients underwent imaging every 3-6 months after treatment to determine best response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) criteria. Responses were categorized as objective response (OR) or nonresponse (NR). Wilcoxon rank sum test evaluated differences in continuous variables, and Pearson χ2 test evaluated differences in categorical variables. RESULTS: Median follow-up was 582 days (IQR, 187-1,227 days). Per RECIST 1.1, 27 patients (75%) experienced OR and 9 patients experienced (25%) NR. Of the 36 patients, 33 (92%) showed hypervascular, mRECIST-evaluable tumors. Among them, 28 patients (85%) showed mRECIST OR and 5 patients (15%) showed NR. The mRECIST OR group received a higher ADT than the NR group (median, 107 Gy; IQR, 95.1-154 Gy vs median, 70.4 Gy; IQR, 62.9-87.6 Gy; P = .048). All tumors receiving at least 120 Gy showed mRECIST OR. CONCLUSIONS: In hypervascular metastatic NET treated by 90Y resin microsphere radioembolization, higher tumor dose was associated with better tumor response per mRECIST. Doses of ≥120 Gy led to OR.

Aberrant oscillatory activity in neurofibromatosis type 1: an EEG study of resting state and working memory.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic neurodevelopmental disorder commonly associated with impaired cognitive function. Despite the well-explored functional roles of neural oscillations in neurotypical populations, only a limited number of studies have investigated oscillatory activity in the NF1 population. METHODS: We compared oscillatory spectral power and theta phase coherence in a paediatric sample with NF1 (N = 16; mean age: 13.03 years; female: n = 7) to an age/sex-matched typically developing control group (N = 16; mean age: 13.34 years; female: n = 7) using electroencephalography measured during rest and during working memory task performance. RESULTS: Relative to typically developing children, the NF1 group displayed higher resting state slow wave power and a lower peak alpha frequency. Moreover, higher theta power and frontoparietal theta phase coherence were observed in the NF1 group during working memory task performance, but these differences disappeared when controlling for baseline (resting state) activity. CONCLUSIONS: Overall, results suggest that NF1 is characterised by aberrant resting state oscillatory activity that may contribute towards the cognitive impairments experienced in this population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03310996 (first posted: October 16, 2017).

Salinization and sedimentation drive contrasting assembly mechanisms of planktonic and sediment-bound bacterial communities in agricultural streams.

Agriculture is the most dominant land use globally and is projected to increase in the future to support a growing human population but also threatens ecosystem structure and services. Bacteria mediate numerous biogeochemical pathways within ecosystems. Therefore, identifying linkages between stressors associated with agricultural land use and responses of bacterial diversity is an important step in understanding and improving resource management. Here, we use the Mississippi Alluvial Plain (MAP) ecoregion, a highly modified agroecosystem, as a case study to better understand agriculturally associated drivers of stream bacterial diversity and assembly mechanisms. In the MAP, we found that planktonic bacterial communities were strongly influenced by salinity. Tolerant taxa increased with increasing ion concentrations, likely driving homogenous selection which accounted for ~90% of assembly processes. Sediment bacterial phylogenetic diversity increased with increasing agricultural land use and was influenced by sediment particle size, with assembly mechanisms shifting from homogenous to variable selection as differences in median particle size increased. Within individual streams, sediment heterogeneity was correlated with bacterial diversity and a subsidy-stress relationship along the particle size gradient was observed. Planktonic and sediment communities within the same stream also diverged as sediment particle size decreased. Nutrients including carbon, nitrogen, and phosphorus, which tend to be elevated in agroecosystems, were also associated with detectable shifts in bacterial community structure. Collectively, our results establish that two understudied variables, salinity and sediment texture, are the primary drivers of bacterial diversity within the studied agroecosystem, whereas nutrients are secondary drivers. Although numerous macrobiological communities respond negatively, we observed increasing bacterial diversity in response to agricultural stressors including salinization and sedimentation. Elevated taxonomic and phylogenetic bacterial diversity likely increases the probability of detecting community responses to stressors. Thus, bacteria community responses may be more reliable for establishing water quality goals within highly modified agroecosystems that have experienced shifting baselines.

Predictive Partition Dosimetry and Outcomes after Yttrium-90 Resin Microsphere Radioembolization of Colorectal Cancer Metastatic to the Liver: A Retrospective Analysis.

PURPOSE: To characterize estimated absorbed tumor dose (ADT), objective response (OR), and estimated target dose of liver metastatic colorectal cancer (mCRC) after resin microsphere yttrium-90 (90Y) radioembolization using partition dosimetry. MATERIALS AND METHODS: In this retrospective, single-center study, multicompartment dosimetry of index tumors undergoing 90Y radioembolization from October 2013 to July 2022 was performed using MIM SurePlan and pretreatment technetium-99m macroaggregated albumin infusion data. Thirty-eight patients with mCRC underwent treatments for 59 index tumors. Patients were imaged every 2-3 months after treatment and then every 3-6 months after disease control to determine the best response per Response Evaluation Criteria in Solid Tumors 1.1. Responses were categorized as OR or nonresponse (NR). A Cox proportional hazards model evaluated the probability of tumor OR and local progression-free survival (LPFS) based on ADT. RESULTS: Patients had a median follow-up of 116 days (interquartile range [IQR], 69-231 days). The ADT was higher for OR patients than for NR patients (median, 130.8 [IQR, 85.6-239.0] vs 40.6 [IQR, 26.0-66.3] Gy; P < .001). A greater percentage of OR than NR patients were treated with activities calculated by partition modeling (54% vs 12%; P = .005). Only ADT predicted response (P = .032). At 6 months, an ADT of 120 Gy predicted a 55% (95% CI, 0.0%-89%) probability of OR. Only ADT (P = .010) and female sex (P = .014) predicted LPFS. At 1 year, an ADT of 120 Gy predicted a 70% (95% CI, 35%-100%) probability of LPFS. CONCLUSIONS: Tumor dose was the strongest predictor of OR for mCRC. Administration of an estimated 120 Gy to mCRC predicted 55% OR with 90Y resin microspheres at 6 months.

Endoscopic Imaging of Pancreatic Cysts.

Pancreatic cystic lesions (PCLs) have been diagnosed with increasing frequency likely due to the widespread use of cross-sectional imaging. A precise diagnosis of the PCL is important because it helps identify patients in need of surgical resection and those who can undergo surveillance imaging. A combination of clinical and imaging findings as well as cyst fluid markers can help classify PCLs and guide management. This review focuses on endoscopic imaging of PCLs including endoscopic and endosonographic features and fine needle aspiration. We then review the role of adjunct techniques, such as microforceps, contrast-enhanced endoscopic ultrasound, pancreatoscopy, and confocal laser endomicroscopy.

Experimental investigation of training schedule on home-based working memory training in healthy older adults.

Introduction: The efficacy of working memory training (WMT) for cognitive enhancement in healthy older adults has been extensively investigated. Typically, WMT results in improved performance on the training task, but limited or no transfer of improvement to other cognitive tasks. Accordingly, there is a need to identify optimal intervention parameters to maximize training and transfer task effects of WMT. The current study aimed to investigate the effect of training schedule on training and transfer task performance of WMT in healthy older adults. A secondary aim was to examine the feasibility of participants performing the intervention online at home, unsupervised, and using their personal devices. Methods: Participants (N = 71; mean age: 66 years) completed sixteen WMT or active-control sessions over eight (distributed) or four (intensive) weeks. Adaptive verbal and spatial n-back tasks were used as the WMT tasks. We tested near transfer effects to a digit-span task and far transfer effects to an abstract relational reasoning task. Results: Participants successfully performed the cognitively demanding intervention using their own devices, online at home, and with minimal contact with the researcher. We observed a significant improvement in WMT task performance in the WMT group relative to active-controls, but no evidence of near or far transfer. Similar training effects were observed irrespective of the intensity of the training schedule. Discussion: Our results suggest that comparable benefits could be observed when using less intensive schedules that may be more easily accommodated into everyday life.

SMAC Mimetics Synergistically Cooperate with HDAC Inhibitors Enhancing TNF-α Autocrine Signaling.

The overexpression of inhibitor of apoptosis (IAP) proteins is strongly related to poor survival of women with ovarian cancer. Recurrent ovarian cancers resist apoptosis due to the dysregulation of IAP proteins. Mechanistically, Second Mitochondrial Activator of Caspases (SMAC) mimetics suppress the functions of IAP proteins to restore apoptotic pathways resulting in tumor death. We previously conducted a phase 2 clinical trial of the single-agent SMAC mimetic birinapant and observed minimal drug response in women with recurrent ovarian cancer despite demonstrating on-target activity. Accordingly, we performed a high-throughput screening matrix to identify synergistic drug combinations with birinapant. SMAC mimetics in combination with an HDAC inhibitor showed remarkable synergy and was, therefore, selected for further evaluation. We show here that this synergy observed both in vitro and in vivo results from multiple convergent pathways to include increased caspase activation, HDAC inhibitor-mediated TNF-α upregulation, and alternative NF-kB signaling. These findings provide a rationale for the integration of SMAC mimetics and HDAC inhibitors in clinical trials for recurrent ovarian cancer where treatment options are still limited.

Attentional Features of Mindfulness are Better Predictors of Face Recognition than Empathy and Compassion-Based Constructs.

Recent research has employed measures of either empathy, compassion or mindfulness and linked better face recognition memory to higher scores of identification with all humanity and mindfulness but not empathy or compassion. Additionally, empathy, compassion and mindfulness have been suggested as concepts that intertwine, but research has not yet examined how their respective personality questionnaires map onto latent concepts. We employed these measures together to explore their factor structure and, using structural equation modelling, we investigated if the suggested latent variables predict recognition memory performance for face and non-face stimuli. Attentional notions of mindfulness described a latent factor that predicted face recognition. All self-compassion facets and the non-react mindfulness facet described a latent factor, which predicted false alarms in face recognition. Finally, empathy and compassion-based notions described one latent factor, which did not predict recognition performance. None of the latent variables predicted performance in either object or voice recognition. Collectively, findings indicate attention-based mindfulness to benefit face recognition, prompting further research into the potential of mindfulness to support the face recognition process.

Timing of percutaneous endoscopic gastrostomy tube placement in post-stroke patients does not impact mortality, complications, or outcomes.

BACKGROUND: Percutaneous Endoscopic Gastrostomy (PEG) tubes are often placed for dysphagia following a stroke in order to maintain sufficient caloric intake. The 2011 ASGE guidelines recommend delaying PEG tube placement for two weeks, as half of patients with dysphagia improve within 2 wk. There are few studies comparing outcomes based on timing of PEG tube placement, and there is increasing demand for early PEG tube placement to meet requirements for timely discharge to rehab and skilled nursing facilities. AIM: To assess the safety of early (≤ 7 d post stroke) vs late (> 7 d post stroke) PEG tube placement and evaluate whether pre-procedural risk factors could predict mortality or complications. METHODS: We performed a retrospective study of patients undergoing PEG tube placement for dysphagia following a stroke at two hospitals in Saint Louis, MO between January 2011 and December 2017. Patients were identified by keyword search of endoscopy reports. Mortality, peri-procedural complication rates, and post-procedural complication rates were compared in both groups. Predictors of morbidity and mortality such as protein-calorie malnutrition, presence of an independent cardiovascular risk equivalent, and presence of Systemic inflammatory response syndrome (SIRS) criteria or documented infection were evaluated by multivariate logistic regression. RESULTS: 154 patients had a PEG tube placed for dysphagia following a stroke, 92 in the late group and 62 in the early group. There were 32 observed deaths, with 8 occurring within 30 d of the procedure. There was an increase in peri-procedural and post-procedural complications with delayed PEG placement which was not statistically significant. Hospital length of stay was significantly less in patients with early PEG tube placement (12.9 vs 22.34 d, P < 0.001). Protein calorie malnutrition, presence of SIRS criteria and/or documented infection prior to procedure or having a cardiovascular disease risk equivalent did not significantly predict mortality or complications. CONCLUSION: Early PEG tube placement following a stroke did not result in a higher rate of mortality or complications and significantly decreased hospital length of stay. Given similar safety outcomes in both groups, early PEG tube placement should be considered in the appropriate patient to potentially reduce length of hospital stay and incurred costs.

Ecological integrity and conservation challenges in a rapidly changing Arctic: A call for new approaches in large intact landscapes.

Intactness is a commonly used measure of ecological integrity, especially when evaluating conservation status at the landscape scale. We argue that in the large and relatively unfragmented landscapes of the Arctic and sub-Arctic, intactness provides only partial insight for managers charged with maintaining ecological integrity. A recent landscape assessment suggests that 95% of Alaska shows no measured direct or indirect impacts of human development on the landscape. However, the current exceptionally high levels of intactness in Alaska, and throughout the Arctic and sub-Arctic, do not adequately reflect impacts to the region's ecological integrity caused by indirect stressors, such as a rapidly changing climate and the subsequent loss of the cryosphere. Thus, it can be difficult to measure, and manage, some of the conservation challenges presented by the ecological context of these systems. The dominant drivers of change, and their associated ecological and socioeconomic impacts, vary as systems decline in ecological integrity from very high to high, and to intermediate levels, but this is not well understood in the literature. Arctic and sub-Arctic systems, as well as other large intact areas, provide unique opportunities for conservation planning, but require tools and approaches appropriate to unfragmented landscapes undergoing rapid climate-driven ecological transformation. We conclude with possible directions for developing more appropriate metrics for measuring ecological integrity in these systems.

The Bumpy Road to Stem Cell Therapies: Rational Design of Surface Topographies to Dictate Stem Cell Mechanotransduction and Fate.

Cells sense and respond to a variety of physical cues from their surrounding microenvironment, and these are interpreted through mechanotransductive processes to inform their behavior. These mechanisms have particular relevance to stem cells, where control of stem cell proliferation, potency, and differentiation is key to their successful application in regenerative medicine. It is increasingly recognized that surface micro- and nanotopographies influence stem cell behavior and may represent a powerful tool with which to direct the morphology and fate of stem cells. Current progress toward this goal has been driven by combined advances in fabrication technologies and cell biology. Here, the capacity to generate precisely defined micro- and nanoscale topographies has facilitated the studies that provide knowledge of the mechanotransducive processes that govern the cellular response as well as knowledge of the specific features that can drive cells toward a defined differentiation outcome. However, the path forward is not fully defined, and the "bumpy road" that lays ahead must be crossed before the full potential of these approaches can be fully exploited. This review focuses on the challenges and opportunities in applying micro- and nanotopographies to dictate stem cell fate for regenerative medicine. Here, key techniques used to produce topographic features are reviewed, such as photolithography, block copolymer lithography, electron beam lithography, nanoimprint lithography, soft lithography, scanning probe lithography, colloidal lithography, electrospinning, and surface roughening, alongside their advantages and disadvantages. The biological impacts of surface topographies are then discussed, including the current understanding of the mechanotransductive mechanisms by which these cues are interpreted by the cells, as well as the specific effects of surface topographies on cell differentiation and fate. Finally, considerations in translating these technologies and their future prospects are evaluated.

The effects of transcranial alternating current stimulation on memory performance in healthy adults: A systematic review.

The recent introduction of Transcranial Alternating Current stimulation (tACS) in research on memory modulation has yielded some exciting findings. Whilst evidence suggests small but significant modulatory effects of tACS on perception and cognition, it is unclear how effective tACS is at modulating memory, and the neural oscillations underlying memory. The aim of this systematic review was to determine the efficacy with which tACS, compared to sham stimulation, can modify working memory (WM) and long-term memory (LTM) performance in healthy adults. We examined how these effects may be moderated by specific tACS parameters and study/participant characteristics. Our secondary goal was to investigate the neural correlates of tACS' effects on memory performance in healthy adults. A systematic search of eight databases yielded 11,413 records, resulting in 34 papers that included 104 eligible studies. The results were synthesised by memory type (WM/LTM) and according to the specific parameters of frequency band, stimulation montage, individual variability, cognitive demand, and phase. A second synthesis examined the correspondence between tACS' effects on memory performance and the oscillatory features of electroencephalography (EEG) and magnetencephalography (MEG) recordings in a subset of 26 studies. The results showed a small-to-medium effect of tACS on WM and LTM performance overall. There was strong evidence to suggest that posterior theta-tACS modulates WM performance, whilst the modulation of LTM is achieved by anterior gamma-tACS. Moreover, there was a correspondence between tACS effects on memory performance and oscillatory outcomes at the stimulation frequency. We discuss limitations in the field and suggest ways to improve our understanding of tACS efficacy to ensure a transition of tACS from an investigative method to a therapeutic tool.

Cognitive and Electrophysiological Correlates of Working Memory Impairments in Neurofibromatosis Type 1.

Neurofibromatosis 1 (NF1) is a single gene disorder associated with working Memory (WM) impairments. The aim of this study was to investigate P300 event-related potential (ERP) associated with WM in NF1. Sixteen adolescents with NF1 were compared with controls on measures of WM and EEG was recorded during a WM nback task. The NF1 group showed poorer performance on measures of WM as compared to the control group. No group differences were observed in P300 amplitude at Pz, but P300 latency was shorter in the NF1 group. Topographic analyses of P300 amplitude showed group differences indicating neural processing differences in the NF1 group relative to controls, which possibly contribute to the cognitive deficits seen in this population.

Morning and evening salivary cortisol levels in patients with chronic widespread pain and those at high risk.

BACKGROUND: Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation has been implicated in chronic widespread pain (CWP); the hallmark of fibromyalgia (FM). This is the first study to compare HPA axis changes in individuals with CWP and those at high risk of symptom development. METHODS: We sought to determine differences in morning and evening salivary cortisol levels in FM (n = 19), those at-risk (n = 20) and pain-free controls (n = 17). Risk factors included non-CWP pain, somatic symptoms, illness behaviour and sleep disturbance. We conducted the study in the absence of centrally acting medication, to address limitations of previous research. RESULTS: Repeated measures ANOVA revealed significant main effects of group (p = 0.003), and time of day (p = 0.002), with no significant interaction. Cortisol levels were higher in FM (p = 0.027) and at-risk (p = 0.003) groups, compared to controls, but there was no significant difference between FM and at-risk groups. The main effect of group remained significant with sleep problems (p = 0.021) and life events (p = 0.007), but was not significant with anxiety (p = 0.076) or depression (p = 0.098) scores as covariates. With sleep problems as a covariate, cortisol levels remained significantly higher only in the at-risk group (p = 0.017). CONCLUSIONS: This study indicates elevated salivary cortisol in FM and those at high risk, and identifies anxiety, depression and sleep problems as potential contributing factors. The results shed light on the dynamic relationship between stress, mood and sleep disorders and the brain's resilience to pain. SIGNIFICANCE: This study examines neurobiological changes in chronic widespread pain and high risk individuals. One strength of the study is the absence of centrally acting medication. We found high salivary cortisol common to Fibromyalgia and those at risk and identified contributing factors. Our results offer insight into the early mechanistic changes underlying Fibromyalgia development and open up possibilities for early diagnosis and prevention.

Abdominal Actinomycosis Abscess Presenting as an Isolated Gastrointestinal Pseudotumor.

Actinomyces is a gram-positive anaerobic bacterium that is ubiquitous in nature. It typically presents as respiratory, cervicofacial, or abdominopelvic abscesses. We present a 66-year-old man with a progressive enlarging abdominal wall nodule concerning for malignancy. The patient had a negative workup, including an ultrasound-guided fine-needle aspiration and colonoscopy, with biopsy for a possible extension to the colonic wall. Diagnosis of an Actinomyces abscess was obtained through surgical resection with right hemicolectomy. He was successfully treated with a prolonged course of intravenous antibiotics. This is a rare case of an isolated abdominal wall Actinomyces abscess mimicking a gastrointestinal malignancy.