Big Data Foretells Future Health

Readily available information can be used to make predictions about population and individual health, which can change the healthcare trajectory of patients, experts report.
Medscape Medical News

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Developmental origin of long-range neurons in the superficial dorsal spinal cord

Abstract

The dorsal spinal cord, which is essential for somatosensory transmission, comprises a heterogeneous population of neurons with distinct axonal lengths and projection patterns. Although the developmental origin of local-circuit interneurons in the dorsal spinal cord has been well characterized, that of long-range neurons extending axons over a long distance such as supraspinal projection neurons and propriospinal neurons is largely unknown. In the present study, we performed birthdate and lineage analyses of these long-range neurons in the mouse dorsal spinal cord. Unilateral injection of a retrograde neuronal tracer, cholera toxin B, into the brain or spinal cord efficiently labeled supraspinal projection neurons localized in Rexed's lamina I and the dorsolateral funiculus (DLF) and long-range propriospinal neurons localized in the DLF, all of which had ipsi- and contra-laterally projecting populations. Most of these neurons were born between E9.5 and E10.5, much earlier than in the case of the neurogenesis of local-circuit neurons. Lineage analysis using an Lbx1-Cre mouse line demonstrated that most long-range neurons were derived from Lbx1-positive neuronal progenitors, except in the case of the contralaterally projecting propriospinal neurons. Characterization of their neurotransmitter identity revealed that almost all of the supraspinal projection neurons were excitatory, whereas the long-range propriospinal neurons comprised both excitatory and inhibitory populations. These results suggest that the supraspinal projection neurons were derived from the early-born dI5 progenitor domain and that the long-range propriospinal ones arose from several early-born progenitor domains.

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Sustained cell body reactivity and loss of NeuN in a subset of axotomized bulbospinal neurons after a chronic high cervical spinal cord injury

Abstract

Following central nervous system lesion, the ability of injured axons to regrowth may depend on the level and duration of the injured cell body response (CBR). Therefore, in order to investigate whether axotomized brainstem neurons maintain a durable growth-competent state after spinal cord injury, we studied the effect of a chronic C2 hemisection in rats on the expression of various CBR markers involved in axon regeneration, such as c-Jun, ATF-3, HSP27, NO synthase (NOS), and also of the neural mature phenotype marker NeuN, in the bulbospinal respiratory neurons as compared to the Gigantocellularis nucleus. Both at 7 and 30 days post-lesion (DPL), c-Jun and HSP27 were present in respectively ~60% and ~20% of the axotomized respiratory neurons, whereas the apoptotic factor caspase 3 was not detected in these cells. NOS appeared belatedly and it was detected in ~20% of the axotomized respiratory neurons at 30DPL. At 30DPL, these different CBR markers were strongly colocalized in a sub-population of axotomized respiratory neurons and also in a sub-population of injured neurons within the gigantocellularis nucleus. Such CBR was also accompanied by a sustained alteration of the neural mature phenotype, as indicated by a loss of NeuN immunoreactivity selectively in HSP27⁺ bulbospinal neurons at 7DPL and 30DPL. Altogether, this study shows that a subset of axotomized medullary respiratory neurons remains in a growth-competent state after a chronic injury, suggesting that they may play a preferential role in long-lasting respiratory neuroplasticity processes.

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Expression of the Cholecystokinin-B Receptor in Neoplastic Gastric Cells

Abstract

Gastric cancer is an important disease due to its high mortality. Despite the decline in frequency, most cases are discovered late in its course, and most of the cancer patients die within a few years of diagnosis. In addition to Helicobacter pylori gastritis, gastrin is considered an important factor in the development of this disease, and thus, cholecystokinin-B receptor (CCKBR) becomes of interest. The aim of our study was to explore whether CCKBR is expressed in stomach cancers. Thirty-seven tumors from 19 men and 18 women diagnosed with either adenocarcinoma or neuroendocrine neoplasm (NENs) were included in this study. The tumors were classified into 29 adenocarcinomas and eight NENs. Immunohistochemistry with antibodies against chromogranin A (CgA), synaptophysin and CCKBR, and in situ hybridization with probes against CgA, CCKBR and histidine decarboxylase were used to further explore these tumors. Thirty-three (89%) of the tumors expressed CCKBR protein, whereas only 20 (54%) of all tumors expressed CCKBR mRNA. Of the 20 tumors expressing CCKBR mRNA, eight were NENs and 12 were adenocarcinoma. The highest amount of CCKBR was expressed in NEN. Interestingly, a high degree of co-expression of CCKBR and CgA was observed when the two markers were examined together with in situ hybridization. In conclusion, we found that all eight NENs expressed CCKBR and neuroendocrine markers in a majority of tumor cells. The same markers were also expressed in a proportion of adenocarcinomas supporting the view that gastrin is important in the development of gastric cancer.

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Encoding Deficits Impede Word Learning and Memory in Adults With Developmental Language Disorders

Purpose

The aim of this study was to determine whether the word-learning challenges associated with developmental language disorder (DLD) result from encoding or retention deficits.

Method

In Study 1, 59 postsecondary students with DLD and 60 with normal development (ND) took the California Verbal Learning Test–Second Edition, Adult Version (Delis, Kramer, Kaplan, & Ober, 2000). In Study 2, 23 postsecondary students with DLD and 24 with ND attempted to learn 9 novel words in each of 3 training conditions: uncued test, cued test, and no test (passive study). Retention was measured 1 day and 1 week later.

Results

By the end of training, students with DLD had encoded fewer familiar words (Study 1) and fewer novel words (Study 2) than their ND peers as evinced by word recall. They also demonstrated poorer encoding as evinced by slower growth in recall from Trials 1 to 2 (Studies 1 and 2), less semantic clustering of recalled words, and poorer recognition (Study 1). The DLD and ND groups were similar in the relative amount of information they could recall after retention periods of 5 and 20 min (Study 1). After a 1-day retention period, the DLD group recalled less information that had been encoded via passive study, but they performed as well as their ND peers when recalling information that had been encoded via tests (Study 2). Compared to passive study, encoding via tests also resulted in more robust lexical engagement after a 1-week retention for DLD and ND groups.

Conclusions

Encoding, not retention, is the problematic stage of word learning for adults with DLD. Self-testing with feedback lessens the deficit.

Supplemental Materials

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from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/doi/10.1044/2017_JSLHR-L-17-0031/2657170/Encoding-Deficits-Impede-Word-Learning-and-Memory

Causes of death and competing risk analysis of the associated factors for non-small cell lung cancer using the Surveillance, Epidemiology, and End Results database

Abstract

Purpose

To investigate the probability of death (POD) from any causes by time after diagnosis of non-small cell lung cancer (NSCLC) and the factors associated with survival for NSCLC patients.

Methods

A total of 202,914 patients with NSCLC from 2004 to 2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The overall survival (OS) and lung cancer-specific survival (LCSS) were calculated and POD from any causes at different time periods after diagnosis was explored. The predictive factors for OS, LCSS and survival from non-lung cancer deaths were investigated using multivariate analysis with Cox proportional hazards regression and competing risk regression analysis.

Results

The 5- and 10-year OS were 20.4% and 11.5%, accordingly that for LCSS were 25.5% and 18.4%, respectively. Lung cancer contributed 88.3% (n = 128,402) of the deaths. The POD from lung cancer decreased with time after diagnosis. In multivariate analysis, advanced age and advanced stage of NSCLC were associated with decreased OS and LCSS. Comparing to no surgery, any kind of resection conferred lower risk of death from lung cancer and higher risk of dying from non-lung cancer conditions except lobectomy or bilobectomy, which was associated with lower risk of death from both lung cancer and non-lung cancer conditions.

Conclusions

Most of the patients with NSCLC died from lung cancer. Rational surveillance and treatment policies should be made for them. Early stage and lobectomy or bilobectomy were associated with improved OS and LCSS. It is reasonable to focus on early detection and optimal surgical treatment for NSCLC.

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Pansclerotic morphea associated with hypohidrosis and anti-M3 muscarinic acetylcholine receptor antibodies

Abstract

A man in his 50s was referred to our hospital due to a 3-month history of extensive hypohidrosis that he first realized in his upper trunk. He subsequently noticed tenseness of the skin on the hypohidrotic areas. He had a medical history of hyperlipidemia, duodenum ulcer and obsessive-compulsive disorder, but had not received drugs known to induce sclerosis or hypohidrosis. Physical examination showed diffuse, shiny, mildly sclerotic skin with a symmetrical distribution in the upper extremities and the trunk; however, the hands, axillae and lateral chest were spared (Figure 1a).

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“The importance of surgical maneuvers during treatment of frontal migraines (site I): a prospective, randomized cohort study evaluating foraminotomy/fasciotomy, myectomy, and arterectomy”

Publication date: Available online 3 October 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): James R. Gatherwright, Yuewei Wu-Fienberg, Bahman Guyuron
BackgroundThe current prospective, blinded, randomized cohort study aims to delineate the relative contribution of different surgical treatments for frontal migraines.MethodsPatients undergoing migraine surgery in the frontal region (site I) were prospectively enrolled and blindly randomized into one of the following four groups: (1) myectomy alone, (2) myectomy and foraminotomy/fasciotomy, (3) myectomy and arterectomy, and (4) foraminotomy/fasciotomy alone. Pre- and post-surgical migraine headache severity, duration, and Migraine Headache Index (MHI) score, as well as migraine-free days (MFDs) were obtained.ResultsThirteen patients agreed to participate in the study. For all patients, the mean pre- and post-operative MHI scores demonstrated a significant improvement from 52.6 (3.8–85) to 4.7 (0–21.3), respectively (p=0.0001). Thirty-one percent of patients required a site I revision that included an arterectomy. Patients who had an arterectomy at their initial surgery demonstrated statistically significant improvement in both frequency (12 vs 6.11; p=0.02) and MHI scores (51.71 vs. 5.55; p<0.01). Arterectomy patients also demonstrated a significant improvement in the number of MFDs following surgery, from 18 to 24 MFDs (p=0.021). Those patients not undergoing arterectomy demonstrated statistically significant improvements in the number of MFDs after their initial surgery (13.25 MFDs, p=0.01), but the improvement was significantly less when compared to the arterectomy group (13.25 vs. 24 MFDs; p=0.026). Following revision arterectomy, both groups had statistically equivalent improvement in MFDs (20.75 vs 24 MFDs; p=0.178).ConclusionsThese findings suggest that arterectomy is necessary for successful treatment of frontal migraines (site I).



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Antibiotic prophylaxis in breast reduction surgery: a different approach

Publication date: Available online 3 October 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): David Boccara, Clair Couteau, Marc Chaouat, Maurice Mimoun, Kevin Serror




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Plastic surgical operative workload in major trauma centres (POW-MTC): a UK prospective national cohort study

Publication date: Available online 4 October 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): S.A. Hendrickson, G.S. Phillips, K. Young, M.D. Gardiner, S. Hettiaratchy




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Unravelling cortical pathology in multiple sclerosis using the T1-/T2-weighted ratio?

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Significance of the Tentorial Alignment in Protecting the Occipital Lobe with the Poppen Approach for Tentorial or Pineal Area Meningiomas

Publication date: December 2017
Source:World Neurosurgery, Volume 108
Author(s): Deling Li, Haoyu Zhang, Wang Jia, Liwei Zhang, Junting Zhang, Weiming Liu, Ming Ni, Guijun Jia
ObjectiveWe aimed to identify the factors that can predict the risk of occipital lobe damage preoperatively when resecting tumors located at the tentorial or pineal regions with the occipital-transtentorial approach (Poppen approach).MethodsIn 27 consecutive patients who underwent tumor resection with the Poppen approach for tentorial or pineal region meningiomas, the following morphologic parameters were assessed on a preoperative magnetic resonance imaging: (1) tentorial angle, (2) tentorial length, and (3) the shortest distance from the confluence of the sinus to the tumor. These parameters, together with tumor size, texture, and resection extent, were correlated with occipital lobe damage by using the one-way analysis of variance, χ², or Fisher's exact tests.ResultsThe mean value was 55.3° ± 5.6° (range, 45°–66°) for the tentorial angle, which was significantly associated with the occipital lobe damage grades (P = 0.008), but this was not the case for the tentorial length (P = 0.802) and the shortest distance from the confluence of the sinus to the tumor (P = 0.695). Interestingly, age was also strongly associated with occipital lobe damage risk (P = 0.020). The patients in the subgroup with no occipital damage (grade 4) were the youngest (aged 47.3 years), compared with other grades, with age of 58.0 years for grade 1, 54.3 years for grade 2, and 58.6 years for grade 3. These 2 parameters were also significant after multivariate analysis. No correlation was observed between either tumor nature or the extent of resection and damage grades.ConclusionsThe risk of occipital lobe damage increases in the presence of a steep tentorial angle during the Poppen approach for tentorial or pineal area tumors. Awareness of such anatomic features preoperatively is important for minimizing operative complications.



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A Retrospective Study of Clinical Outcomes After Endovascular Treatment in Acute Ischemic Stroke Patients with Complete Anterior Circulation Infarction in the Absence of Multimodal Computed Tomography

Publication date: December 2017
Source:World Neurosurgery, Volume 108
Author(s): Chenghua Xu, Anyang Tao, Zhimin Wang, Yi Zhang, Xiaoxiao Tao, Huaping Xin, Xian Zheng, Jiangxian Ying, Peng Wang
ObjectiveTo analyze the positive predictive value of large artery occlusion and clinical prognosis in acute ischemic stroke patients with total anterior circulation infarct (TACI) who underwent endovascular treatment in the absence of multimodal CT angiography or CT perfusion.MethodsThe inclusion criteria for the acute ischemic stroke patients to receive endovascular treatment were as the follows: the Oxfordshire Community Stroke Project classification was TACI, Alberta Stroke Program Early Computed Tomography Score (ASPECTS) ≥ 6, National Institutes of Health stroke scale (NIHSS) score ≥8, and less than 4.5 hours since stroke onset. The endovascular treatment was performed on patients who met the inclusion criteria. The endovascular treatment included intra-arterial thrombolysis, mechanical treatments, or both. A retrospective analysis was performed on all eligible acute ischemic stroke patients who underwent endovascular treatment from January 1, 2015 to December 31, 2015.ResultsA total of 17 patients met the inclusion criteria and underwent endovascular treatment. The median age was 76 years (range, 59–88 years). 12 patients (70.6%) were diagnosed with atrial fibrillation. 16 patients were diagnosed with large artery occlusion by digital subtraction angiography, and the positive predictive value was 94.1%. 16 patients (94.1%) had recanalization (TICI Grade 3); 12 patients (70.6%) had a modified Rankin Scale score of 0–2, and 1 patient (5.9%) died 90 days after treatment.ConclusionsIn the absence of multimodal CT, endovascular treatment might be beneficial to patients with TACI acute ischemic stroke within 4.5 hours of stroke onset, who had NIHSS score of 8 or greater and ASPECTS of 6 or greater. These inclusion criteria have a high positive predictive value for anterior circulation large artery occlusion.



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Phase I study of a chloroquine–gemcitabine combination in patients with metastatic or unresectable pancreatic cancer

Abstract

Purpose

Following a previously published pre-clinical validation, this phase I study evaluated the safety, maximum tolerated dose, anti-tumour activity and immune status of a gemcitabine–chloroquine combination as a first- or late-line treatment in patients with metastatic or unresectable pancreatic cancer.

Methods

In this 3 + 3 dose escalation study, patients received a single weekly standard dose of intravenous gemcitabine, followed by single weekly oral intake of 100, 200 or 300 mg of chloroquine. Tumour response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. Immune status was evaluated by RT-PCR to measure the relative expression of immune-related genes in peripheral blood mononuclear cells (PBMCs).

Results

Overall, nine patients [median age 72 years; interquartile range (IQR), 68–78 years] were treated. No dose-limiting toxicities as defined in the protocol were observed. Three patients experienced partial response, and two patients had stable disease. The median time to progression was 4 months (95% CI 0.8–7.2), and the median overall survival was 7.6 months (95% CI 5.3–9.9). Among 86 assayed immune genes, three were significantly differentially expressed in PBMCs from responding versus non-responding patients: interferon-gamma receptor-1, toll-like receptor 2, and beta-2 microglobulin.

Conclusions

The addition of chloroquine to gemcitabine was well tolerated and showed promising effects on the clinical response to the anti-cancer chemotherapy. Based on these initial results, the efficacy of the gemcitabine–chloroquine combination should be further assessed.

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Prior Learning of Relevant Nonaversive Information Is a Boundary Condition for Avoidance Memory Reconsolidation in the Rat Hippocampus

Reactivated memories can be modified during reconsolidation, making this process a potential therapeutic target for posttraumatic stress disorder (PTSD), a mental illness characterized by the recurring avoidance of situations that evoke trauma-related fears. However, avoidance memory reconsolidation depends on a set of still loosely defined boundary conditions, limiting the translational value of basic research. In particular, the involvement of the hippocampus in fear-motivated avoidance memory reconsolidation remains controversial. Combining behavioral and electrophysiological analyses in male Wistar rats, we found that previous learning of relevant nonaversive information is essential to elicit the participation of the hippocampus in avoidance memory reconsolidation, which is associated with an increase in theta- and gamma-oscillation power and cross-frequency coupling in dorsal CA1 during reactivation of the avoidance response. Our results indicate that the hippocampus is involved in memory reconsolidation only when reactivation results in contradictory representations regarding the consequences of avoidance and suggest that robust nesting of hippocampal theta–gamma rhythms at the time of retrieval is a specific reconsolidation marker.

SIGNIFICANCE STATEMENT Posttraumatic stress disorder (PTSD) is characterized by maladaptive avoidance responses to stimuli or behaviors that represent or bear resemblance to some aspect of a traumatic experience. Disruption of reconsolidation, the process by which reactivated memories become susceptible to modifications, is a promising approach for treating PTSD patients. However, much of what is known about fear-motivated avoidance memory reconsolidation derives from studies based on fear conditioning instead of avoidance-learning paradigms. Using a step-down inhibitory avoidance task in rats, we found that the hippocampus is involved in memory reconsolidation only when the animals acquired the avoidance response in an environment that they had previously learned as safe and showed that increased theta- and gamma-oscillation coupling during reactivation is an electrophysiological signature of this process.

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Should a Few Null Findings Falsify Prefrontal Theories of Conscious Perception?

Is activity in prefrontal cortex (PFC) critical for conscious perception? Major theories of consciousness make distinct predictions about the role of PFC, providing an opportunity to arbitrate between these views empirically. Here we address three common misconceptions: (1) PFC lesions do not affect subjective perception; (2) PFC activity does not reflect specific perceptual content; and (3) PFC involvement in studies of perceptual awareness is solely driven by the need to make reports required by the experimental tasks rather than subjective experience per se. These claims are incompatible with empirical findings, unless one focuses only on studies using methods with limited sensitivity. The literature highlights PFC's essential role in enabling the subjective experience in perception, contra the objective capacity to perform visual tasks; conflating the two can also be a source of confusion.

Dual Perspectives Companion Paper: Are the Neural Correlates of Consciousness in the Front or in the Back of the Cerebral Cortex? Clinical and Neuroimaging Evidence, by Melanie Boly, Marcello Massimini, Naotsugu Tsuchiya, Bradley R. Postle, Christof Koch, and Giulio Tononi

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Action Potential Broadening in Capsaicin-Sensitive DRG Neurons from Frequency-Dependent Reduction of Kv3 Current

Action potential (AP) shape is a key determinant of cellular electrophysiological behavior. We found that in small-diameter, capsaicin-sensitive dorsal root ganglia neurons corresponding to nociceptors (from rats of either sex), stimulation at frequencies as low as 1 Hz produced progressive broadening of the APs. Stimulation at 10 Hz for 3 s resulted in an increase in AP width by an average of 76 ± 7% at 22°C and by 38 ± 3% at 35°C. AP clamp experiments showed that spike broadening results from frequency-dependent reduction of potassium current during spike repolarization. The major current responsible for frequency-dependent reduction of overall spike-repolarizing potassium current was identified as Kv3 current by its sensitivity to low concentrations of 4-aminopyridine (IC₅₀ <100 μm) and block by the peptide inhibitor blood depressing substance I (BDS-I). There was a small component of Kv1-mediated current during AP repolarization, but this current did not show frequency-dependent reduction. In a small fraction of cells, there was a component of calcium-dependent potassium current that showed frequency-dependent reduction, but the contribution to overall potassium current reduction was almost always much smaller than that of Kv3-mediated current. These results show that Kv3 channels make a major contribution to spike repolarization in small-diameter DRG neurons and undergo frequency-dependent reduction, leading to spike broadening at moderate firing frequencies. Spike broadening from frequency-dependent reduction in Kv3 current could mitigate the frequency-dependent decreases in conduction velocity typical of C-fiber axons.

SIGNIFICANCE STATEMENT Small-diameter dorsal root ganglia (DRG) neurons mediating nociception and other sensory modalities express many types of potassium channels, but how they combine to control firing patterns and conduction is not well understood. We found that action potentials of small-diameter rat DRG neurons showed spike broadening at frequencies as low as 1 Hz and that spike broadening resulted predominantly from frequency-dependent inactivation of Kv3 channels. Spike width helps to control transmitter release, conduction velocity, and firing patterns and understanding the role of particular potassium channels can help to guide new pharmacological strategies for targeting pain-sensing neurons selectively.

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Are the Neural Correlates of Consciousness in the Front or in the Back of the Cerebral Cortex? Clinical and Neuroimaging Evidence

The role of the frontal cortex in consciousness remains a matter of debate. In this Perspective, we will critically review the clinical and neuroimaging evidence for the involvement of the front versus the back of the cortex in specifying conscious contents and discuss promising research avenues.

Dual Perspectives Companion Paper: Should a Few Null Findings Falsify Prefrontal Theories of Conscious Perception?, by Brian Odegaard, Robert T. Knight, and Hakwan Lau

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Stopping Inflammation in Stroke: Role of ST2/IL-33 Signaling

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Reward-Related Ventral Striatum Activity Buffers against the Experience of Depressive Symptoms Associated with Sleep Disturbances

Sleep disturbances represent one risk factor for depression. Reward-related brain function, particularly the activity of the ventral striatum (VS), has been identified as a potential buffer against stress-related depression. We were therefore interested in testing whether reward-related VS activity would moderate the effect of sleep disturbances on depression in a large cohort of young adults. Data were available from 1129 university students (mean age 19.71 ± 1.25 years; 637 women) who completed a reward-related functional MRI task to assay VS activity and provided self-reports of sleep using the Pittsburgh Sleep Quality Index and symptoms of depression using a summation of the General Distress/Depression and Anhedonic Depression subscales of the Mood and Anxiety Symptoms Questionnaire-short form. Analyses revealed that as VS activity increased the association between sleep disturbances and depressive symptoms decreased. The interaction between sleep disturbances and VS activity was robust to the inclusion of sex, age, race/ethnicity, past or present clinical disorder, early and recent life stress, and anxiety symptoms, as well as the interactions between VS activity and early or recent life stress as covariates. We provide initial evidence that high reward-related VS activity may buffer against depressive symptoms associated with poor sleep. Our analyses help advance an emerging literature supporting the importance of individual differences in reward-related brain function as a potential biomarker of relative risk for depression.

SIGNIFICANCE STATEMENT Sleep disturbances are a common risk factor for depression. An emerging literature suggests that reward-related activity of the ventral striatum (VS), a brain region critical for motivation and goal-directed behavior, may buffer against the effect of negative experiences on the development of depression. Using data from a large sample of 1129 university students we demonstrate that as reward-related VS activity increases, the link between sleep disturbances and depression decreases. This finding contributes to accumulating research demonstrating that reward-related brain function may be a useful biomarker of relative risk for depression in the context of negative experiences.

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