Egocentric cues influence the allocentric spatial memory of object configurations for memory-guided actions.

Allocentric and egocentric reference frames are used to code the spatial position of action targets in reference to objects in the environment, i.e., relative to landmarks (allocentric), or the observer (egocentric). Previous research investigated reference frames in isolation, for example, by shifting landmarks relative to the target and asking participants to reach to the remembered target location. Systematic reaching errors were found in the direction of the landmark shift and used as a proxy for allocentric spatial coding. Here, we examined the interaction of both allocentric and egocentric reference frames by shifting the landmarks as well as the observer. We asked participants to encode a three-dimensional configuration of balls and to reproduce this configuration from memory after a short delay followed by a landmark or an observer shift. We also manipulated the number of landmarks to test its effect on the use of allocentric and egocentric reference frames. We found that participants were less accurate when reproducing the configuration of balls after an observer shift, which was reflected in larger configurational errors. In addition, an increase in the number of landmarks led to a stronger reliance on allocentric cues and a weaker contribution of egocentric cues. In sum, our results highlight the important role of egocentric cues for allocentric spatial coding in the context of memory-guided actions.NEW & NOTEWORTHY Objects in our environment are coded relative to each other (allocentrically) and are thought to serve as independent and reliable cues (landmarks) in the context of unreliable egocentric signals. Contrary to this assumption, we demonstrate that egocentric cues alter the allocentric spatial memory, which could reflect recently discovered interactions between allocentric and egocentric neural processing pathways. Furthermore, additional landmarks lead to a higher contribution of allocentric and a lower contribution of egocentric cues.

Health-related quality of life 2 years after pedicle subtraction osteotomy for sagittal imbalance: a single-center experience of 65 patients.

PURPOSE: Pedicle subtraction osteotomy (PSO) as an invasive procedure with high reoperation and complication rates in an often elderly population has often been questioned. The purpose of our study was to evaluate the impact of PSO for sagittal imbalance (SI) on patient-reported outcomes including self-reported satisfaction and health-related quality of life 2 years postoperatively. METHODS: Consecutive patients who underwent correction of their spinal deformity by thoracolumbar PSO were assessed using self-reporting questionnaires 2 years postoperatively. Outcome was measured by visual analogue scale (VAS) for back and leg pain, Oswestry Disability Index (ODI), and EQ-5D scores. Additionally, a Patient Satisfaction Index (PSI) rated in four grades (A: very satisfied to D: not satisfied), walking range, and the Timed Up and Go (TUG) Test were evaluated. RESULTS: Sixty-five patients were included, and each parameter was assessed preoperatively and 24 months postoperatively. The intervention led to significant improvements in back pain (8.1 ± 1.2 vs. 2.9 ± 1.9; p < 0.001), as well as ODI scores (57.7 ± 13.9 vs. 32.6 ± 18.9; p < 0.001), walking range (589 ± 1676 m vs. 3265 ± 3405 m; p < 0.001), and TUG (19.2 s vs. 9.7 s; p < 0.05). 90.7% of patients (n = 59/65) reported a PSI grade "A" or "B" 24 months postoperatively. CONCLUSION: Patient satisfaction 24 months after PSO for SI is high. Quality of life improved significantly by restoring sagittal balance.

Hippocampal neuroinflammation following combined exposure to cyclophosphamide and naproxen in ovariectomized mice.

Aim: Cancer patients undergoing chemotherapy report cognitive changes collectively termed "chemo brain." Neuroinflammation is among the factors believed to contribute to "chemo brain" suggesting a potential beneficial role for anti-inflammatory drugs in cancer patients undergoing chemotherapy. We investigated whether the non-steroidal anti-inflammatory drug naproxen influenced hippocampal inflammation in non-tumor bearing female mice receiving the chemotherapy drug cyclophosphamide (CP).Materials and methods: Intact and ovariectomized C57BL/6 mice were used to examine potential role of ovarian hormones on neuroinflammation. The mice were placed on naproxen (375 ppm) or control diet, and a week later CP (100 mg/kg; i.p.) was administered every 3 days for 2 weeks. We analyzed hippocampal inflammatory biomarkers, anxiety-like behavior, spatial working memory, exploratory behavior, spontaneous locomotor activity and depression-like behavior.Results: CP produced significant effects on anti-inflammatory but not pro-inflammatory biomarkers. However, CP and naproxen in combination produced significant effects on both pro- and anti- inflammatory biomarkers. Naproxen and ovariectomy individually produced significant effects on pro- and anti-inflammatory biomarkers as well. Working memory and depression-like behavior were not significantly influenced by CP, naproxen or ovariectomy individually although CP and ovariectomy produced significant interaction effects on depression-like behavior. Exploratory behavior and locomotor activity showed significant effects of CP, and interaction between CP and naproxen was significant for locomotor activity.Conclusions: Ovariectomy, naproxen and a combination of CP and naproxen upregulate hippocampal pro- and anti- inflammatory biomarkers. None of the factors individually produce significant behavioral changes that could be consistent with chemo brain, although CP and ovariectomy in combination produced significant effects on depression-like behavior, a co-morbidity of chemo brain.

Time-limited alterations in cortical activity of a knock-in mouse model of KCNQ2-related developmental and epileptic encephalopathy.

De novo missense variants in the KCNQ2 gene encoding the Kv7.2 subunit of voltage-gated potassium Kv7/M channels are the main cause of developmental and epileptic encephalopathy with neonatal onset. Although seizures usually resolve during development, cognitive/motor deficits persist. To gain a better understanding of the cellular mechanisms underlying network dysfunction and their progression over time, we investigated in vivo, using local field potential recordings of freely moving animals, and ex vivo in layers II/III and V of motor cortical slices, using patch-clamp recordings, the electrophysiological properties of pyramidal cells from a heterozygous knock-in mouse model carrying the Kv7.2 p.T274M pathogenic variant during neonatal, postweaning and juvenile developmental stages. We found that knock-in mice displayed spontaneous seizures preferentially at postweaning rather than at juvenile stages. At the cellular level, the variant led to a reduction in M ​​current density/conductance and to neuronal hyperexcitability. These alterations were observed during the neonatal period in pyramidal cells of layers II/III and during the postweaning stage in pyramidal cells of layer V. Moreover, there was an increase in the frequency of spontaneous network-driven events mediated by GABA receptors, suggesting that the excitability of interneurons was also increased. However, all these alterations were no longer observed in layers II/III and V of juvenile mice. Thus, our data indicate that the action of the variant is regulated developmentally. This raises the possibility that the age-related seizure remission observed in KCNQ2-related developmental and epileptic encephalopathy patients results from a time-limited alteration of Kv7 channel activity and neuronal excitability. KEY POINTS: The electrophysiological impact of the pathogenic c.821C>T mutation of the KCNQ2 gene (p.T274M variant in Kv7.2 subunit) related to developmental and epileptic encephalopathy has been analysed both in vivo and ex vivo in layers II/III and V of motor cortical slices from a knock-in mouse model during development at neonatal, postweaning and juvenile stages. M current density and conductance are decreased and the excitability of layer II/III pyramidal cells is increased in slices from neonatal and postweaning knock-in mice but not from juvenile knock-in mice. M current and excitability of layer V pyramidal cells are impacted in knock-in mice only at the postweaning stage. Spontaneous GABAergic network-driven events can be recorded until the postweaning stage, and their frequency is increased in layers II/III of the knock-in mice. Knock-in mice display spontaneous seizures preferentially at postweaning rather than at juvenile stages.

Prevalence of self-reported memory problems in adults with type 2 diabetes mellitus and cancer in the USA.

PURPOSE: To determine the prevalence of memory problems in individuals with or without a history of DM and cancer and assess possible compounding effects of these diseases on self-reported memory problems (SRMP). METHODS: We used data from the 2009-2018 National Health and Nutrition Examination Survey. We conducted logistic regression analyses to determine the associations among DM, cancer, and SRMP, adjusting for age, sex, race/ethnicity, education, and poverty level. We examined the interaction effects of comorbid DM and cancer on SRMP. We compared participants with both DM and cancer to those with cancer only and to those with no DM or cancer. RESULTS: We included 26,842 adults ≥ 20 years old (N = 3374 with DM, N = 23,468 without DM) and 51.87% female. There were 10,434 Whites, 5730 Blacks, 6795 Hispanics, and 3883 other races/multiracial. More individuals with DM reported memory problems than those without DM (p < 0.0001). More individuals with cancer reported memory problems than those without cancer (p < 0.0001). Of those with both DM and cancer, 14.19% reported memory problems. More individuals with DM had cancer than those without DM (p < 0.0001). Of those with both diseases, 55.75% had DM before the cancer diagnosis. DM (odds ratio[OR] = 1.87, 95%CI, 1.55-2.26) and cancer (OR = 1.81, 95%CI, 1.43-2.30) predicted SRMP. The interaction between DM and cancer was significant, and the likelihood of having both diseases compared to having neither DM nor cancer was OR = 2.09, 95%CI, 1.41 - 3.11. CONCLUSION: Strategies to mitigate SRMP in individuals with comorbid DM and cancer history should consider the impact of both diseases.

Flexing a standard hinge-powered operating table for lumbosacral three-column osteotomy (3-CO) site closure in 84 consecutive patients.

Three-column osteotomy (3-CO) is a powerful technique in adult deformity surgery, and pedicle subtraction osteotomy (PSO) is the workhorse to correct severe kyphotic spinal deformities. Aging of the population, increasing cases of iatrogenic flat back deformities and understanding the importance of sagittal balance have led to a dramatic increase of this surgical technique. Surgery, however, is demanding and associated with high complication rates so that every step of the procedure requires meticulous technique. Particularly, osteotomy closure is associated with risks like secondary fracture, translation, or iatrogenic stenosis. This step is traditionally performed by compression or a cantilever maneuver with sometimes excessive forces on the screws or instrumentation. Implant loosening or abrupt subluxation resulting in construct failure and/or neurological deficits can result. The aim of this prospective registry study was to assess the efficacy and safety of our surgical PSO technique as well as the osteotomy closure by flexing a hinge-powered OR table. In a series of 84 consecutive lumbosacral 3-CO, a standardized surgical technique with special focus on closure of the osteotomy was prospectively evaluated. The surgical steps with the patients positioned prone on a soft frame are detailed. Osteotomy closure was achieved by remote controlled bending of a standard OR table without compressive or cantilever forces in all 84 cases. This technique carries a number of advantages, particularly the reversibility and the slow speed of closure with minimum force. There was not a single mechanical intraoperative complication such as vertebral body fracture, subluxation, or adjacent implant loosening during osteotomy closure, compared to external cohorts using the cantilever technique (p = 0.130). The feasibility of controlled 3-CO closure by flexing a standard OR table is demonstrated. This technique enables a safe, gentle closure of the osteotomy site with minimal risk of implant failure or accidental neurological injury.

FUSE-ML: development and external validation of a clinical prediction model for mid-term outcomes after lumbar spinal fusion for degenerative disease.

BACKGROUND: Indications and outcomes in lumbar spinal fusion for degenerative disease are notoriously heterogenous. Selected subsets of patients show remarkable benefit. However, their objective identification is often difficult. Decision-making may be improved with reliable prediction of long-term outcomes for each individual patient, improving patient selection and avoiding ineffective procedures. METHODS: Clinical prediction models for long-term functional impairment [Oswestry Disability Index (ODI) or Core Outcome Measures Index (COMI)], back pain, and leg pain after lumbar fusion for degenerative disease were developed. Achievement of the minimum clinically important difference at 12 months postoperatively was defined as a reduction from baseline of at least 15 points for ODI, 2.2 points for COMI, or 2 points for pain severity. RESULTS: Models were developed and integrated into a web-app ( https://neurosurgery.shinyapps.io/fuseml/ ) based on a multinational cohort [N = 817; 42.7% male; mean (SD) age: 61.19 (12.36) years]. At external validation [N = 298; 35.6% male; mean (SD) age: 59.73 (12.64) years], areas under the curves for functional impairment [0.67, 95% confidence interval (CI): 0.59-0.74], back pain (0.72, 95%CI: 0.64-0.79), and leg pain (0.64, 95%CI: 0.54-0.73) demonstrated moderate ability to identify patients who are likely to benefit from surgery. Models demonstrated fair calibration of the predicted probabilities. CONCLUSIONS: Outcomes after lumbar spinal fusion for degenerative disease remain difficult to predict. Although assistive clinical prediction models can help in quantifying potential benefits of surgery and the externally validated FUSE-ML tool may aid in individualized risk-benefit estimation, truly impacting clinical practice in the era of "personalized medicine" necessitates more robust tools in this patient population.

Focal Dorsal Hippocampal Nav1.1 Knock Down Alters Place Cell Temporal Coordination and Spatial Behavior.

Alterations in the voltage-gated sodium channel Nav.1.1 are implicated in various neurological disorders, including epilepsy, Alzheimer's disease, and autism spectrum disorders. Previous studies suggest that the reduction of Nav1.1 expression leads to a decrease of fast spiking activity in inhibitory neurons. Because interneurons (INs) play a critical role in the temporal organization of neuronal discharge, we hypothesize that Nav1.1 dysfunction will negatively impact neuronal coordination in vivo. Using shRNA interference, we induced a focal Nav1.1 knock-down (KD) in the dorsal region of the right hippocampus of adult rats. Focal, unilateral Nav1.1 KD decreases the performance in a spatial novelty recognition task and the firing rate in INs, but not in pyramidal cells. It reduced theta/gamma coupling of hippocampal oscillations and induced a shift in pyramidal cell theta phase preference. Nav1.1 KD degraded spatial accuracy and temporal coding properties of place cells, such as theta phase precession and compression of ongoing sequences. Aken together, these data demonstrate that a deficit in Nav1.1 alters the temporal coordination of neuronal firing in CA1 and impairs behaviors that rely on the integrity of this network. They highlight the potential contribution of local inhibition in neuronal coordination and its impact on behavior in pathological conditions.

Early surgery determines recovery of motor deficits in lumbar disc herniations-a prospective single-center study.

BACKGROUND: Patients with intervertebral disc herniation undergo surgical removal of herniated disc material in cases of persisting symptoms and/or neurologic deficits. While motor deficits often prompt surgery, little is known about the optimal timing of surgery in these cases. The aim of this study was to prospectively evaluate the impact of timing of disc surgery on motor recovery. Does postponing surgical treatment worsen outcome? METHOD: In total, 120 patients with sciatica and/or sensorimotor deficits due to a lumbar disc herniation were surgically treated at the authors' center within a 3-month period. In 60 patients, motor deficits were present at the time of admission. Motor function was assessed using manual muscle testing and subdivided according to the Medical Research Council (MRC) scale. Patient demographics, neurologic deficits, duration of motor deficits, treatment characteristics, and outcome were assessed. At a minimum follow-up of 1 year, functional recovery and complications were collated. Patients were subdivided into groups according to the severity of the paresis (MRC ≤ 3/5 vs. MRC 4/5). Intra-group differences were compared based on the duration of the neurologic deficits. RESULTS: Patients with moderate and severe paresis (MRC ≤ 3/5) benefit from treatment within 72 h as they were shown to have a significantly higher complete recovery rate at 1-year follow-up (75% vs. 0%; p < 0.001). CONCLUSION: Immediate surgery should be offered to patients with moderate and severe motor deficits to increase the likelihood of neurologic recovery. This prospective data may have an impact on emergency triage in these patients.

A knock-in mouse model for KCNQ2-related epileptic encephalopathy displays spontaneous generalized seizures and cognitive impairment.

OBJECTIVE: Early onset epileptic encephalopathy with suppression-burst is one of the most severe epilepsy phenotypes in human patients. A significant proportion of cases have a genetic origin, and the most frequently mutated gene is KCNQ2, encoding Kv7.2, a voltage-dependent potassium channel subunit, leading to so-called KCNQ2-related epileptic encephalopathy (KCNQ2-REE). To study the pathophysiology of KCNQ2-REE in detail and to provide a relevant preclinical model, we generated and described a knock-in mouse model carrying the recurrent p.(Thr274Met) variant. METHODS: We introduced the p.(Thr274Met) variant by homologous recombination in embryonic stem cells, injected into C57Bl/6N blastocysts and implanted in pseudopregnant mice. Mice were then bred with 129Sv Cre-deleter to generate heterozygous mice carrying the p.(Thr274Met), and animals were maintained on the 129Sv genetic background. We studied the development of this new model and performed in vivo electroencephalographic (EEG) recordings, neuroanatomical studies at different time points, and multiple behavioral tests. RESULTS: The Kcnq2Thr274Met/+ mice are viable and display generalized spontaneous seizures first observed between postnatal day 20 (P20) and P30. In vivo EEG recordings show that the paroxysmal events observed macroscopically are epileptic seizures. The brain of the Kcnq2Thr274Met/+ animals does not display major structural defects, similar to humans, and their body weight is normal. Kcnq2Thr274Met/+ mice have a reduced life span, with a peak of unexpected death occurring for 25% of the animals by 3 months of age. Epileptic seizures were generally not observed when animals grew older. Behavioral characterization reveals important deficits in spatial learning and memory in adults but no gross abnormality during early neurosensory development. SIGNIFICANCE: Taken together, our results indicate that we have generated a relevant model to study the pathophysiology of KCNQ2-related epileptic encephalopathy and perform preclinical research for that devastating and currently intractable disease.

Item-level psychometrics of a brief self-reported memory problem screening measure in breast cancer survivors.

Background: We previously developed and psychometrically validated a self-reported memory problem (SRMP) measure using principal component analysis. In the present study, we applied item response theory (IRT) analysis to further examined the construct validity and determine item-level psychometric properties for the SRMP.Methods: The sample included 530 female breast cancer survivors (61% non-Hispanic White, mean age = 57 years) who were recruited from community-based organizations and large health care systems. We examined the construct validity, item-level psychometric properties, and differential item functioning (DIF) of the SRMP using confirmatory factor analysis (CFA), IRT and logistic regression analysis models.Results: The CFA confirmed a one-factor structure for the SRMP (comparative fit index [CFI] = 0.996, root-mean-square-error-approximation [RMSEA] = 0.059). As expected, SRMP scores correlated significantly with pain, mood, and fatigue; but not spiritual health locus of control (SPR). DIF analysis showed no measurement differences based on race/ethnicity and age groups.Conclusion: The CFA and DIF analysis supported the construct validity of the SRMP and its use in an ethnically diverse breast cancer population. These findings provide further evidence of the generalizability for the SRMP, and support its utilization as a psychometrically valid and reliable screening measure of cancer and treatment-related memory difficulties.

Patient Satisfaction with Navigator Interpersonal Relationship (PSN-I): item-level psychometrics using IRT analysis.

BACKGROUND: Patient navigation (PN) is a promising intervention to eliminate cancer health inequities. Patient navigators play a critical role in the navigation process. Patients' satisfaction with navigators is important in determining the effectiveness of PN programs. We applied item response theory (IRT) analysis to establish item-level psychometric properties for the Patient Satisfaction with Interpersonal Relationship with Navigators (PSN-I). METHODS: We conducted a confirmatory factor analysis (CFA) to establish unidimensionality of the 9-item PSN-I in 751 cancer patients (68% female) between 18 and 86 years old. We fitted unidimensional IRT models-unconstrained graded response model (GRM) and Rasch model-to PSN-I data, and compared model fit using likelihood ratio (LR) test and information criteria. We obtained item parameter estimates (IPEs), item category/operating characteristic curves, and item/test information curves for the better fitting model. RESULTS: CFA with diagonally weighted least squares confirmed that the one-factor model fit the data (RMSEA = 0.047, 95% CI = 0.033-0.060, and CFI ≈ 1). Responses to PSN-I items clustered into the 4th and 5th categories. We aggregated the first three response categories to provide stable parameter estimates for both IRT models. The GRM fit the data significantly better than the Rasch model (LR = 80.659, df = 8, p < 0.001). Akaike's information coefficient (6384.978 vs. 6320.319) and Bayesian information coefficient (6471.851 vs. 6443.771) were lower for the GRM. IPEs showed substantial variation in items' discriminating power (1.80-3.35) for GRM. CONCLUSIONS: This IRT analysis confirms the latent structure of the PSN-I and supports its use as a valid and reliable measure of latent satisfaction with PN.

Emergence of Coordinated Activity in the Developing Entorhinal-Hippocampal Network.

Correlated activity in the entorhinal-hippocampal neuronal networks, supported by oscillatory and intermittent population activity patterns is critical for learning and memory. However, when and how correlated activity emerges in these networks during development remains largely unknown. Here, we found that during the first postnatal week in non-anaesthetized head-restrained rats, activity in the superficial layers of the medial entorhinal cortex (MEC) and hippocampus was highly correlated, with intermittent population bursts in the MEC followed by early sharp waves (eSPWs) in the hippocampus. Neurons in the superficial MEC layers fired before neurons in the dentate gyrus, CA3 and CA1. eSPW current-source density profiles indicated that perforant/temporoammonic entorhinal inputs and intrinsic hippocampal connections are co-activated during entorhinal-hippocampal activity bursts. Finally, a majority of the entorhinal-hippocampal bursts were triggered by spontaneous myoclonic body movements, characteristic of the neonatal period. Thus, during the neonatal period, activity in the entorhinal cortex (EC) and hippocampus is highly synchronous, with the EC leading hippocampal activation. We propose that such correlated activity is embedded into a large-scale bottom-up circuit that processes somatosensory feedback resulting from neonatal movements, and that it is likely to instruct the development of connections between neocortex and hippocampus.

Psychometric evaluation of the German version of the Patient Satisfaction with Cancer-related Care questionnaire.

BACKGROUND: Patient satisfaction is a fundamental aspect of perceived health care quality. The original English version of the Patient Satisfaction with Cancer-related Care (PSCC) is a psychometrically validated, one-dimensional instrument with relevance to cancer-related care. The goal of the study was to perform a psychometric validation of the PSCC in German (PSCC-G). METHODS: A sample of 394 cancer patients were recruited at oncological clinics in Hamburg, Germany. Patients completed the PSCC-G, three subscales of the Patient Satisfaction and Quality in Oncological Care (PASQOC), and one subscale from the German version of the Recherché Evaluative sur la Performance des Réseaux de Santé (RESPERE-60) questionnaire. We conducted exploratory and confirmatory factor analyses (EFA and CFA) to determine the factorial validity, and we calculated Cronbach's coefficient alpha (α) to test the internal consistency of the PSCC-G. We examined the correlation between the PSCC-G and four subscales measuring additional dimensions of PS with care. We also conducted a multiple linear regression analysis to determine whether sociodemographics, self-perceived health status, and treatment setting predict scores on the PSCC-G. RESULTS: The EFA (using principal axis) revealed a one-factor solution. The Cronbach's α was 0.92. The convergent validity showed high correlations between three different subscales measuring patient satisfaction and the PSCC-G. Overall, males, older age patients, and those with a higher self-perceived health status were more satisfied with their cancer care based on their higher scores on the PSCC-G. CONCLUSION: The PSCC-G is a reliable and valid instrument that can assess satisfaction with cancer-related care for German-speaking cancer patients.

Kyphotic deformity of the lumbar spine due to a monostotic fibrous dysplasia of the second lumbar vertebra: a case report and its surgical management.

Monostotic fibrous dysplasia (MFD) of the lumbar spine represents an exceedingly rare lesion. A 26-year-old patient presented with a progressive osteolytic lesion of the vertebral body L2 and the diagnosis of MFD. A minimally invasive left-sided eXtreme Lateral Interbody Fusion (XLIF) approach with resection of the vertebral body L2 with placement of a mesh cage was performed. No complications were observed perioperatively and the symptoms rapidly improved. Minimally invasive piecemeal resection with a combined dorsolateral approach showed a favorable clinical and radiological outcome and seems to be a safe and reliable technique for MFD.

Impaired vocal communication, sleep-related discharges, and transient alteration of slow-wave sleep in developing mice lacking the GluN2A subunit of N-methyl-d-aspartate receptors.

OBJECTIVE: Glutamate-gated N-methyl-d-aspartate receptors (NMDARs) are instrumental to brain development and functioning. Defects in the GRIN2A gene, encoding the GluN2A subunit of NMDARs, cause slow-wave sleep (SWS)-related disorders of the epilepsy-aphasia spectrum (EAS). The as-yet poorly understood developmental sequence of early EAS-related phenotypes, and the role of GluN2A-containing NMDARs in the development of SWS and associated electroencephalographic (EEG) activity patterns, were investigated in Grin2a knockout (KO) mice. METHODS: Early social communication was investigated by ultrasonic vocalization (USV) recordings; the relationship of electrical activity of the cerebral cortex with SWS was studied using deep local field potential or chronic EEG recordings at various postnatal stages. RESULTS: Grin2a KO pups displayed altered USV and increased occurrence of high-voltage spindles. The pattern of slow-wave activity induced by low-dose isoflurane was altered in Grin2a KO mice in the 3rd postnatal week and at 1 month of age. These alterations included strong suppression of the delta oscillation power and an increase in the occurrence of the spike-wave bursts. The proportion of SWS and the sleep quality were transiently reduced in Grin2a KO mice aged 1 month but recovered by the age of 2 months. Grin2a KO mice also displayed spontaneous spike-wave discharges, which occurred nearly exclusively during SWS, at 1 and 2 months of age. SIGNIFICANCE: The impaired vocal communication, the spike-wave discharges occurring almost exclusively in SWS, and the age-dependent alteration of SWS that were all seen in Grin2a KO mice matched the sleep-related and age-dependent manifestations seen in children with EAS, hence validating the Grin2a KO as a reliable model of EAS disorders. Our data also show that GluN2A-containing NMDARs are involved in slow-wave activity, and that the period of postnatal brain development (postnatal day 30) when several anomalies peaked might be critical for GluN2A-dependent, sleep-related physiological and pathological processes.

Association of externalizing religious and spiritual beliefs on stage of colon cancer diagnosis among black and white multicenter urban patient populations.

BACKGROUND: This study explores whether externalizing religious and spiritual beliefs is associated with advanced-stage colon cancer at initial oncology presentation and whether this association is stronger for blacks than for whites. METHODS: Patients who had newly diagnosed, invasive colon cancer were recruited at 9 sites in the Chicago metropolitan area. Eligible patients were non-Hispanic white or black, ages 30 to 79 years, and diagnosed with a primary invasive colon cancer. Patients were interviewed on prior screening and diagnosis. Social and attitudinal constructs were measured, including the God Locus of Health Control (GLHC) and Religious Problem Solving. The final response rate was 52% and included 407 patients. RESULTS: The median age was 59 years (range, 30-79 years), and 51% of participants were black. Cancer stage was available for 389 (96%) patients and was divided between late stage (stages III-IV; 60%) and early stage (stages I-II; 40%). Multivariate analysis indicated that patients in the highest tertile of scores on the GLHC were more likely have an advanced stage of disease at presentation (odds ratio, 2.14; 95% confidence interval, 1.00-4.59; P = .05) compared with those in the lowest tertile. No significant interaction was identified between race and GLHC scores for stage at presentation (P = .78). CONCLUSIONS: In a large sample of black and white individuals across diverse health care systems, higher scores on the GLHC predicted late disease stage at presentation. Although blacks had significantly higher GLHC scores, race was not associated with stage at presentation, nor was the association between GLHC and stage limited to blacks. Further work is needed to better understand this association and to develop interventions to better connect the religious and health care spheres. Cancer 2018;124:2578-87. © 2018 American Cancer Society.

Effects of patient navigation on satisfaction with cancer care: a systematic review and meta-analysis.

PURPOSE: Patient navigation (PN) is a model of healthcare coordination designed to reduce barriers to achieving optimal health outcomes. Systematic reviews evaluating whether PN is associated with higher patient satisfaction with cancer care are lacking. METHODS: We conducted a systematic review to synthesize evidence of comparative studies evaluating the effectiveness of PN programs to improve satisfaction with cancer-related care. We included studies reported in English that: (1) evaluated a PN intervention designed to increase satisfaction with cancer care; and (2) involved a randomized controlled trial (RCT) or non-RCT approach. Standardized forms were used to abstract data from studies. These data were evaluated for methodological quality, summarized qualitatively, and synthesized under a random effects model. RESULTS: The initial search yielded 831 citations. Nine met inclusion criteria. Five had adequate data (1 RCT and 4 non-RCTs) to include in the meta-analysis. Methodological quality of included studies ranged from weak to strong, with half rated as weak. Findings of the RCTs showed a statistically significant increase in satisfaction with cancer care involving PN (standardized mean difference (SMD) = 2.30; 95% confidence interval 1.79, 2.80, p < 0.001). Pooled results from non-RCTs showed no significant association between PN and satisfaction with cancer-related care (standardized mean difference = 0.39; 95% confidence interval - 0.02, 0.80, p = 0.06). CONCLUSIONS: Although PN has been widely implemented to improve cancer care, high-quality studies are needed to characterize the relationship between PN and satisfaction with cancer-related care.

Thoracic corpectomy for neoplastic vertebral bodies using a navigated lateral extracavitary approach-a single-center consecutive case series: technique and analysis.

Thoracic myelopathy is often caused by vertebral body fractures resulting from neoplastic conditions, traumatic events, or infectious diseases. One of the preferred procedures for treating it is the lateral extracavitary approach (LECA) with single-level or multilevel decompressive corpectomy and reconstruction. The aim of this retrospective study was to analyze the thoracic lateral extracavitary approach with corpectomy using vertebral body replacement systems (VBR-S) and dorsal reconstruction. Twenty-four patients with metastatic or primary lesions of thoracic vertebrae T2-T12 underwent spinal decompression and ventral column reconstruction with correction of spinal deformity via a LECA. One-level to four-level corpectomies were performed with additional navigated dorsal pedicle screw fixation at an average of two levels above and below the corpectomy lesion. None of the patients received preoperative spinal embolization, and the majority of the patients were admitted to radiotherapy postoperatively. Their mean age was 56 years (± 15), with a female-to-male sex ratio of 8 to 16. Patients with a minimum follow-up period of 16 months were included. The Karnofsky index, preoperative and postoperative numeric rating scale (NRS), and Frankel scale were measured. In addition, intraoperative loss of blood (LOB), units of packed red blood cell (PRBC) transfusions, the duration of the operation, and the hospitalization period were evaluated and correlated with preoperative and postoperative values. The majority of the patients were suffering from metastatic lesions and were treated with a 1 level corpectomy (median 1 level, range 1 to 4). The mean duration of surgery was 288 min (± 121) and the mean LOB was 1626 mL (± 1486 mL), with approximately two PRBC units per patient used. All patients were transferred to the intensive care unit (ICU) postoperatively, with a mean ICU stay of 2.0 days (± 1 day). The mean hospitalization period was 13 days (± 7 days). No implant-related failures or procedure-related deaths were observed. Significant differences were noted between the preoperative and postoperative Karnofsky index (74 vs. 84%) and NRS (4 vs. 2). One patient required revision surgery due to a superficial wound infection, and another needed revision surgery due to a dural tear. In another patient, an iatrogenic dural tear was repaired during the same surgical procedure and did not lead to postoperative complications. Four pleural effusions and one pneumothorax were observed, so that the overall complication rate was approximately 33%. Four of the patients died within 2 years of the operation due to progression of the primary disease. Lateral corpectomy and sagittal reconstruction of the thoracic spine using VBR-S conducted via a navigated LECA approach yields favorable results, despite the burden of neoplastic disease. These challenging procedures are accompanied by increased LOB and hospitalization periods, with moderate transfusion requirements. Surgery-related complications are low and local tumor control is satisfactory, despite the progression of the underlying neoplastic disease. However, optimal surgical therapy does not ensure long-term survival.Study design Retrospective analysis of thoracic corpectomiesLevel of evidence 4.

Distinct mechanisms controlling rough and smooth endoplasmic reticulum contacts with mitochondria.

Gp78 (also known as AMFR), an endoplasmic-reticulum (ER)-associated protein degradation (ERAD) E3 ubiquitin ligase, localizes to mitochondria-associated ER and targets the mitofusin (Mfn1 and Mfn2) mitochondrial fusion proteins for degradation. Gp78 is also the cell surface receptor for autocrine motility factor (AMF), which prevents Gp78-dependent mitofusin degradation. Gp78 ubiquitin ligase activity promotes ER-mitochondria association and ER-mitochondria Ca(2+) coupling, processes that are reversed by AMF. Electron microscopy of HT-1080 fibrosarcoma cancer cells identified both smooth ER (SER; ∼8 nm) and wider (∼50-60 nm) rough ER (RER)-mitochondria contacts. Both short hairpin RNA (shRNA)-mediated knockdown of Gp78 (shGp78) and AMF treatment selectively reduced the extent of RER-mitochondria contacts without impacting on SER--mitochondria contacts. Concomitant small interfering RNA (siRNA)-mediated knockdown of Mfn1 increased SER-mitochondria contacts in both control and shGp78 cells, whereas knockdown of Mfn2 increased RER-mitochondria contacts selectively in shGp78 HT-1080 cells. The mitofusins therefore inhibit ER-mitochondria interaction. Regulation of close SER-mitochondria contacts by Mfn1 and of RER-mitochondria contacts by AMF-sensitive Gp78-mediated degradation of Mfn2 define new mechanisms that regulate ER-mitochondria interactions.