Association of rs2073618 polymorphism and osteoprotegerin levels with hypertension and cardiovascular risks in patients with type 2 diabetes mellitus.

There are reports of link of osteoprotegerin (OPG) gene polymorphism to type-2 diabetes (T2D) and hypertension (HTN). The objective of the study was to assess the allele frequency of OPG (rs2073618) gene polymorphism and its association with heart rate variability (HRV) and blood pressure variability profile as CVD risks in diabetes mellitus patients with hypertension undergoing treatment. T2D patients on treatment without hypertension (n = 172), with hypertension (n = 177) and 191 healthy volunteers were recruited for the study. Their blood pressure variability including baroreflex sensitivity (BRS), heart rate variability (HRV), OPG, insulin, lipid profile, receptor-activator for NFkB (RANK), receptor-activator for NFkB-Ligand (RANKL), and tumor necrosis factor-α (TNF-α) were estimated. Allele frequency of OPG (rs2073618) gene polymorphism was assessed from the DNA samples. BRS and HRV indices were decreased, and RANKL/OPG and TNF-α were increased in T2D and T2D + HTN groups, respectively compared to healthy control group. The reduction in BRS was contributed by increased inflammation and reduced SDNN of HRV in GG genotype in T2D + HTN. In GG + GC subgroup, it was additionally contributed by rise in RANKL/OPG level (ß - 0.219; p 0.008). Presence of mutant GG genotype contributed to the risk of hypertension among T2D patients (OR 3.004) as well as in general population (OR 2.79). It was concluded that CV risks are more in T2D patients with HTN expressing OPG rs2073618 gene polymorphism.

Emotional and cognitive processes in psychotherapy are associated with different aspects of the therapeutic relationship.

OBJECTIVE: In this naturalistic study we aimed to investigate the relationships between two central change processes (affective and cognitive) and two common relationship factors ("Confidence in the therapist" and "Confidence in the treatment"), which have been shown to impact outcomes in a clinical context. We also investigated whether these interrelationships varied across treatment orientations (i.e., cognitive or psychodynamic focused). METHOD: The sample consisted of 631 patients with a primary anxiety or depressive disorder who were admitted to an inpatient program and treated with psychotherapy. The data consisted of weekly measures of cognitive (i.e., "rumination") and affective (i.e., "problems with emotional clarity") change processes as well as scores on Confidence in the therapist and Confidence in the treatment and symptom distress. A multivariate version of the latent curve model with structured residuals was used to investigate the within-patient effects of week-to-week changes in all variables. RESULTS: Initial analyses established that both problems with emotional clarity and rumination predicted symptom distress. Further, we found that higher Confidence in the therapist predicted higher emotional clarity (but not lower rumination) whereas higher Confidence in the treatment predicted lower rumination (but did not affect emotional clarity). Post hoc analyses found that these interrelationships varied across treatment orientation (i.e., cognitive vs. psychodynamic). DISCUSSION: The results indicate that patients' experience of the therapist is associated with emotional change processes, and that patients' experience of the coherence and meaningfulness of treatment, on the other hand, is associated with cognitive change processes. Implications for clinical practice are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Symptom Change during Waitlist for Medicated and Nonmedicated Patients with Chronic Depression.

INTRODUCTION: Patients seeking psychotherapy often spend time on waitlist (WL), the effect of which is largely unknown. WL patients may forego alternative non-psychotherapeutic assistance and thus do more poorly than had they not been placed on a WL. The course of symptoms might also be influenced by use of antidepressant medication (ADM), an issue that remains unexplored in the literature. OBJECTIVE: In a naturalistic setting, WL symptom change before inpatient psychotherapy (mean weeks of waiting = 22.6) was assessed in a sample (N = 313) of chronically depressed patients. METHODS: Using the Beck Depression Inventory-II, patients' symptoms were tracked at assessment, when admitted to treatment (i.e., after WL), at posttreatment and 1-year follow-up. Multilevel growth curve analysis was used to examine waitlist change for the whole sample as well as for ADM users and nonmedicated patients. RESULTS: Symptoms were reduced significantly from assessment to admittance (Cohen's d = 0.47). Symptoms reduced less for ADM users (d = 0.39) than for nonmedicated patients (d = 0.65). CONCLUSION: The findings indicate that chronically depressed patients experience a decrease in symptoms during WL, quite likely due to treatment expectations. We discuss whether less symptom improvement for ADM users could be attributed to iatrogenic comorbidity and a higher degree of demoralization in this group.

Decision and response monitoring during working memory are sequentially represented in the human insula.

Emerging research supports a role of the insula in human cognition. Here, we used intracranial EEG to investigate the spatiotemporal dynamics in the insula during a verbal working memory (vWM) task. We found robust effects for theta, beta, and high frequency activity (HFA) during probe presentation requiring a decision. Theta band activity showed differential involvement across left and right insulae while sequential HFA modulations were observed along the anteroposterior axis. HFA in anterior insula tracked decision making and subsequent HFA was observed in posterior insula after the behavioral response. Our results provide electrophysiological evidence of engagement of different insula subregions in both decision-making and response monitoring during vWM and expand our knowledge of the role of the insula in complex human behavior.

Subspace partitioning in the human prefrontal cortex resolves cognitive interference.

The human prefrontal cortex (PFC) constitutes the structural basis underlying flexible cognitive control, where mixed-selective neural populations encode multiple task features to guide subsequent behavior. The mechanisms by which the brain simultaneously encodes multiple task-relevant variables while minimizing interference from task-irrelevant features remain unknown. Leveraging intracranial recordings from the human PFC, we first demonstrate that competition between coexisting representations of past and present task variables incurs a behavioral switch cost. Our results reveal that this interference between past and present states in the PFC is resolved through coding partitioning into distinct low-dimensional neural states; thereby strongly attenuating behavioral switch costs. In sum, these findings uncover a fundamental coding mechanism that constitutes a central building block of flexible cognitive control.

Inter-site generalizability of EEG based age prediction algorithms in the preterm infant.

Objective. To overcome the effects of site differences in EEG-based brain age prediction in preterm infants.Approach. We used a 'bag of features' with a combination function estimated using support vector regression (SVR) and feature selection (filter then wrapper) to predict post-menstrual age (PMA). The SVR was trained on a dataset containing 138 EEG recordings from 37 preterm infants (site 1). A separate set of 36 EEG recordings from 36 preterm infants was used to validate the age predictor (site 2). The feature distributions were compared between sites and a restricted feature set was constructed using only features that were not significantly different between sites. The mean absolute error between predicted age and PMA was used to define the accuracy of prediction and successful validation was defined as no significant differences in error between site 1 (cross-validation) and site 2.Main results. The age predictor based on all features and trained on site 1 was not validated on site 2 (p< 0.001; MAE site 1 = 1.0 weeks,n= 59 versus MAE site 2 = 2.1 weeks,n= 36). The MAE was improved by training on a restricted features set (MAE site 1 = 1.0 weeks,n= 59 versus MAE site 2 = 1.1 weeks,n= 36), resulting in a validated age predictor when applied to site 2 (p= 0.68). The features selected from the restricted feature set when training on site 1 closely aligned with features selected when trained on a combination of data from site 1 and site 2.Significance. The ability of EEG classifiers, such as brain age prediction, to maintain accuracy on data collected at other sites may be challenged by unexpected, site-dependent differences in EEG signals. Permitting a small amount of data leakage between sites improves generalization, leading towards universal methods of EEG interpretation in preterm infants.

Combining MRI and Spectral EEG for Assessment of Neurocognitive Outcomes in Preterm Infants.

INTRODUCTION: Predicting impairment in preterm children is challenging. Our aim is to explore the association between MRI at term-equivalent age (TEA) and neurocognitive outcomes in late childhood and to assess whether the addition of EEG improves prognostication. METHODS: This prospective observational study included forty infants with gestational age 24 + 0-30 + 6. Children were monitored with multichannel EEG for 72 h after birth. Total absolute band power for the delta band on day 2 was calculated. Brain MRI was performed at TEA and scored according to the Kidokoro scoring system. At 10-12 years of age, we evaluated neurocognitive outcomes with Wechsler Intelligence Scale for Children 4th edition, Vineland adaptive behavior scales 2nd edition and Behavior Rating Inventory of Executive Function. We performed linear regression analysis to examine the association between outcomes and MRI and EEG, respectively, and multiple regression analysis to explore the combination of MRI and EEG. RESULTS: Forty infants were included. There was a significant association between global brain abnormality score and composite outcomes of WISC and Vineland test, but not the BRIEF test. The adjusted R2 was 0.16 and 0.08, respectively. For EEG, adjusted R2 was 0.34 and 0.15, respectively. When combining MRI and EEG data, adjusted R2 changed to 0.36 for WISC and 0.16 for the Vineland test. CONCLUSION: There was a small association between TEA MRI and neurocognitive outcomes in late childhood. Adding EEG to the model improved the explained variance. Combining EEG and MRI data did not have any additional benefit over EEG alone.

Whole-exome sequencing in moyamoya patients of Northern-European origin identifies gene variants involved in Nitric Oxide metabolism: A pilot study.

Introduction: Moyamoya disease (MMD) is a chronic cerebrovascular steno-occlusive disease of largely unknown etiology. Variants in the RNF213 gene are strongly associated with MMD in East-Asia. In MMD patients of Northern-European origin, no predominant susceptibility variants have been identified so far. Research question: Are there specific candidate genes associated with MMD of Northern-European origin, including the known RNF213 gene? Can we establish a hypothesis for MMD phenotype and associated genetic variants identified for further research? Material and methods: Adult patients of Northern-European origin, treated surgically for MMD at Oslo University Hospital between October 2018 to January 2019 were asked to participate. WES was performed, with subsequent bioinformatic analysis and variant filtering. The selected candidate genes were either previously reported in MMD or known to be involved in angiogenesis. The variant filtering was based on variant type, location, population frequency, and predicted impact on protein function. Results: Analysis of WES data revealed nine variants of interest in eight genes. Five of those encode proteins involved in nitric oxide (NO) metabolism: NOS3, NR4A3, ITGAV, GRB7 and AGXT2. In the AGXT2 gene, a de novo variant was detected, not previously described in MMD. None harboured the p.R4810K missense variant in the RNF213 gene known to be associated with MMD in East-Asian patients. Discussion and conclusion: Our findings suggest a role for NO regulation pathways in Northern-European MMD and introduce AGXT2 as a new susceptibility gene. This pilot study warrants replication in larger patient cohorts and further functional investigations.

Self-compassion and fear of compassion in the treatment of chronic depression: Mechanisms of change?

OBJECTIVE: The aim of this naturalistic process study was to investigate the relationship between self-compassion, fear of compassion from others, and depressive symptoms over the course of psychotherapy in patients with chronic depression. METHOD: A sample of 226 patients with chronic depression who received inpatient short-term psychodynamic psychotherapy (STPP) provided weekly self-report measures of self-compassion, fear of compassion, and depressive symptoms (Patient Health Questionnaire-9). Trivariate latent curve modeling with structured residuals was applied to investigate the between- and within-patient relationships among the variables. RESULTS: At the between-patient level, a significant positive correlation was found between slope of depression and the slope of fear of compassion. At the within-patient level, a lower than expected level of fear of compassion predicted a subsequent lower than expected level of depression (mean weekly effect size = 0.12), with a smaller reciprocal relationship (mean weekly effect size = 0.08). There was no significant within-patient effect of self-compassion predicting subsequent depression, but a significant effect of a lower than expected level of depression predicting a subsequent higher than expected level of self-compassion (mean weekly effect size = -0.13). No within-patient effect between self-compassion and fear of compassion was found. CONCLUSIONS: In the context of this study, it appears that fear of compassion may be a putative mechanism of change involved in alleviating depressive symptoms in patients with chronic depression treated with STPP. On the other hand, self-compassion appears to be an outcome of psychotherapy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Relationship between Insulin Resistances with Autonomic Functions in Patients with Type 2 Diabetes in South Indian Population.

Cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D) are major health concerns In India. Insulin resistance (IR) itself is a risk factor for CVD. Though it is associated to sympathetic activity this relation may get altered in presence of obesity. Therefore, in the present study we measured the link of IR, with their body mass index (BMI) and the corresponding degree of alteration in various autonomic function tests in T2D patients. It was an observational study conducted in a tertiary care hospital for a period of six months. Eighty-five T2D patients visiting medicine OPD were recruited out of which 17 were normal, 31 were overweight and 31 were obese as per WHO criteria of obesity. Their glucose, insulin, insulin resistance was analyzed in fasting blood samples. Conventional autonomic function tests such as isometric hand-grip test and deep breathing test was digitally recorded. Heart rate variability was recorded as LF: HF ratio. The Rate-pressure product (RPP), the marker of myocardial work stress was calculated from systolic blood pressure and basal heart rate. E: I ratio was calculated from RR interval from ECG tracing. Insulin resistance was positively associated with increased basal heart rate. It was linked to increase LF: HF ratio even after controlling for BMI. Regression analysis showed insulin resistance to be an independent factor for sympathovagal imbalance in T2D patients. The severity of insulin resistance independently predicts degree of deterioration in sympathovagal imbalance as measured in LF: HF ratio in our study which is independent of their degree of obesity.

Hypertension attenuates the link of osteoprotegerin to reduced baroreflex sensitivity in type 2 diabetes mellitus patients on oral antidiabetic and antihypertensive therapy - a cross sectional study.

PURPOSE: Decreased baroreflex sensitivity (BRS) has been shown to be a marker of cardiovascular (CV) risk. In the present study, the difference in CV risk biomarkers in type 2 diabetes (T2D) patients receiving oral antidiabetic drugs (OAD) with and without hypertension has been assessed. MATERIALS AND METHODS: Ninety-two T2D patients on OAD without hypertension (control group) and eighty-eight diabetic patients with hypertension on OAD and antihypertensive drugs (test group) matched for age, gender, body mass index, serum glucose, glycated haemoglobin, and duration of the disease were recruited for the study. Their blood pressure (BP) variability including BRS, heart rate variability (HRV), insulin, lipid profile, osteoprotegerin (OPG), and tumor necrosis factor-α (TNF-α) were estimated. The association of various factors with BRS was assessed by Spearman correlation and multiple regression analysis. RESULTS: BRS was decreased (13.90 ± 5.27 vs 6.76 ± 4.58), HRV sympathetic indices [LFnu, LF-HF ratio (1.30 ± 0.49 vs 1.93 ± 0.62)], HOMA-IR, atherogenic index of plasma (AIP), OPG (223.08 ± 103.86 vs 287.60 ± 121.36) and TNF-α were increased, and parasympathetic indices [TP (1012.90 ± 316.18 vs 625.88 ± 229.84), RMSSD, SDNN, NN50, pNN50] were decreased in the test group compared to control group. In control group, parasympathetic indices, AIP, OPG, and TNF-α had a significant correlation and OPG had an independent association (ß - 0.344; p 0.004) with BRS. In test group, BP, LF-HF ratio, parasympathetic indices, AIP, OPG, and TNF-α had significant correlation, and TNF-α alone (ß - 0.297; p 0.022) had an independent contribution to decreased BRS. CONCLUSION: Despite antidiabetic and antihypertensive treatments, T2D patients with hypertension had more cardiometabolic risks in comparison to normotensive T2D patients. Inflammation could be the inciting factor for rise in BP and decrease in BRS (CV risk) in hypertensive T2D patients. Hypertension in diabetes could attenuate the link of OPG to the reduction in BRS. Reduction in BRS could be a physiological marker of CV risk in T2D patients treated with OAD.

Cardiovagal modulation and oxidative stress in hypothyroidism on maintenance therapy.

AIM: To analyze the autonomic control of heart rate variability (HRV) in subjects with peripheral hypothroidism undergoing hormone replacement therapy with L-thyroxine (L-T4) for 5-10 years. METHODS: Thyroid profile, lipid profile, lipid-risk factors, parameters of oxidative stress [malondialdehyde (MDA)], inflammation [high-sensitive C-reactive protein (CRP)] and Heart rate variability (HRV) was analyzed in thirty-eight hypothyroid patients on treatment for more than five years and compared with healthy euthyroid volunteers of similar age, gender, and body composition. The link of oxidative stress with HRV parameters was assessed by Spearman-Rho correlation and regression analyses. RESULTS: Hypothyroid patients on L-T4 treatment, had higher TSH (p<0.01), lipid profile (p<0.05) and lipid risk factors (p<0.05), high-sensitive C-reactive-protein (hsCRP) (3.31 versus 4.95 mg/L; p<0.05) and MDA (2.66 versus 6.87 µm/L; p <0.001) in serum. There was gross reduction in HRV parameters [reduced standard deviation of NN interval (SDNN), root mean square of successive differences between normal heartbeats (RMSSD), total power (TP) and elevated ratio of low to high frequency power (LF/HF ratio)] in patients. Elevated MDA was correlated with vagal withdrawal (decreased SDNN, RMSSD and TP) and TSH. In multiple regression analysis TSH and TP contributed to the rise in MDA. CONCLUSION: Hormone replacement therapy with L-T4 for hypothyroidism alone does not resolve persistent hyperlipidemia, oxidative stress and inflammation in primary hypothyroid patients even after five years of treatment. Association of oxidative stress with reduced cardiovagal modulation in these patients suggests persistence of cardiovascular risk despite standard treatment which warrants further investigation.

Orbitofrontal cortex governs working memory for temporal order.

How do we think about time? Converging lesion and neuroimaging evidence indicates that orbitofrontal cortex (OFC) supports the encoding and retrieval of temporal context in long-term memory1, which may contribute to confabulation in individuals with OFC damage2. Here, we reveal that OFC damage diminishes working memory for temporal order, that is, the ability to disentangle the relative recency of events as they unfold. OFC lesions reduced working memory for temporal order but not spatial position, and individual deficits were commensurate with lesion size. Comparable effects were absent in patients with lesions restricted to lateral prefrontal cortex (PFC). Based on these findings, we propose that OFC supports understanding of the order of events. Well-documented behavioral changes in individuals with OFC damage2 may relate to impaired temporal-order understanding.

Emotional clarity and tolerance of emotional distress as mechanisms of change in short-term psychodynamic psychotherapy for chronic depression.

OBJECTIVE: The aim of this naturalistic process study was to investigate the relationship between emotional clarity and tolerance of emotional distress and depressive symptoms over the course of short-term psychodynamic psychotherapy for chronically depressed patients. METHOD: Weekly self-reports of emotional clarity, tolerance of emotional distress, and depressive symptoms (PHQ-9) were provided by 252 patients with chronic depression who were admitted to a 13-week inpatient treatment program. Latent curve modeling with structured residuals (LCM-SR) was applied to investigate the between- and within-person effects of week-to-week change in emotional clarity and tolerance of emotional distress as predictors of subsequent depression. The relationship between emotional clarity and tolerance of emotional distress was also investigated. RESULTS: At the within-person level, higher level of emotional clarity and tolerance of emotional distress predicted subsequent lower level of depression. A reciprocal relationship was found for tolerance of emotional distress (lower level of depression predicted subsequent level of tolerance emotional distress) but not for emotional clarity. No within-person effect between emotional clarity and tolerance of emotional distress was found. DISCUSSION: The results indicate that emotional clarity and tolerance of emotional distress may be mechanisms of change in short-term psychodynamic psychotherapy for chronic depression. The results are consistent with previous findings of the importance of emotional clarity and tolerance of emotional distress in psychotherapy. This study demonstrated the utility of LCM-SR as a method to identity mechanisms of change in psychotherapy. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Early spectral EEG in preterm infants correlates with neurocognitive outcomes in late childhood.

BACKGROUND: Evidence regarding the predictive value of early amplitude-integrated electroencephalography (aEEG)/EEG on neurodevelopmental outcomes at school age and beyond is lacking. We  aimed to investigate whether there is an association between early postnatal EEG and neurocognitive outcomes in late childhood. METHODS: This study is an observational prospective cohort study of premature infants with a gestational age <28 weeks. The total absolute band powers (tABP) of the delta, theta, alpha, and beta bands were analyzed from EEG recordings during the first three days of life. At 10-12 years of age, neurocognitive outcomes were assessed using the Wechsler Intelligence Scale for Children 4th edition (WISC-IV), Vineland adaptive behavior scales 2nd edition, and Behavior Rating Inventory of Executive Function (BRIEF). The mean differences in tABP were assessed for individuals with normal versus unfavorable neurocognitive scores. RESULTS: Twenty-two infants were included. tABP values in all four frequency bands were significantly lower in infants with unfavorable results in the main composite scores (full intelligence quotient, adaptive behavior composite score, and global executive composite score) on all three tests (p < 0.05). CONCLUSIONS: Early postnatal EEG has the potential to assist in predicting cognitive outcomes at 10-12 years of age in extremely premature infants <28 weeks' gestation. IMPACT: Evidence regarding the value of early postnatal EEG in long-term prognostication in preterm infants is limited. Our study suggests that early EEG spectral analysis correlates with neurocognitive outcomes in late childhood in extremely preterm infants. Early identification of infants at-risk of later impairment is important to initiate early and targeted follow-up and intervention.

It's the therapist and the treatment: The structure of common therapeutic relationship factors.

Objective: Prior research has established that common therapeutic relationship factors are potent predictors of change in psychotherapy, but such factors are typically studied one at a time and their underlying structure when studied simultaneously is not clear. We assembled empirically validated relationship factors (e.g., therapist empathy; patient expectations; agreement about goals) into a single instrument and subjected it to factor analysis. Method: The instrument was applied to patients (N = 332) undergoing intensive psychotherapy of different types for depressive disorders, anxiety disorders, eating disorders, and childhood trauma in an inpatient specialized mental health setting. In order to examine the psychometric properties of the scale, we used half the sample (N=164) to conduct exploratory factor analysis (EFA) and parallel analysis before we tested the solution using exploratory structural equation modeling (ESEM) on the second half of the sample (N=168). Measurement invariance analysis was conducted to examine the stability of the factor structure. Results: The analysis yielded two factors, which were termed 1. "Confidence in the therapist" and 2. "Confidence in the treatment." Discussion: When assessed simultaneously, patients differentiate between their evaluation of the therapist and of the treatment. The results indicate that there is substantial overlap among previously established relationship factors.Trial registration: ClinicalTrials.gov identifier: NCT03503981.

Role of Ventromedial Hypothalamus in Sucrose-Induced Obesity on Metabolic Parameters.

BACKGROUND: Obesity is because of excessive fat accumulation that affects health adversely in the form of various diseases such as diabetes, hypertension, cardiovascular diseases, and many other disorders. Our Indian diet is rich in carbohydrates, and hence the sucrose-induced obesity is an apt model to mimic this. Ventromedial hypothalamus (VMH) is linked to the regulation of food intake in animals as well as humans. PURPOSE: To understand the role of VMHin sucrose-induced obesity on metabolic parameters. METHODS: A total of 24 adult rats were made obese by feeding them on a 32% sucrose solution for 10 weeks. The VMH nucleus was ablated in the experimental group and sham lesions were made in the control group. Food intake, body weight, and biochemical parameters were compared before and after the lesion. RESULTS: Male rats had a significant weight gain along with hyperphagia, whereas female rats did not have a significant weight gain inspite of hyperphagia. Insulin resistance and dyslipidemia were seen in both the experimental and control groups. CONCLUSION: A sucrose diet produces obesity which is similar to the metabolic syndrome with insulin resistance and dyslipidemia, and a VMH lesion further exaggerates it. Males are more prone to this exaggeration.

Intracranial Recordings Demonstrate Both Cortical and Medial Temporal Lobe Engagement in Visual Search in Humans.

Visual search is a fundamental human behavior, providing a gateway to understanding other sensory domains as well as the role of search in higher-order cognition. Search has been proposed to include two component processes: inefficient search (Search) and efficient search (Pop-out). According to extant research, these two processes map onto two separable neural systems located in the frontal and parietal association cortices. In this study, we use intracranial recordings from 23 participants to delineate the neural correlates of Search and Pop-out with an unprecedented combination of spatiotemporal resolution and coverage across cortical and subcortical structures. First, we demonstrate a role for the medial temporal lobe in visual search, on par with engagement in frontal and parietal association cortex. Second, we show a gradient of increasing engagement over anatomical space from dorsal to ventral lateral frontal cortex. Third, we confirm previous intracranial work demonstrating nearly complete overlap in neural engagement across cortical regions in Search and Pop-out. We further demonstrate Pop-out selectivity, manifesting as activity increase in Pop-out as compared to Search, in a distributed set of sites including frontal cortex. This result is at odds with the view that Pop-out is implemented in low-level visual cortex or parietal cortex alone. Finally, we affirm a central role for the right lateral frontal cortex in Search.

Endophyte roles in nutrient acquisition, root system architecture development and oxidative stress tolerance.

Plants associate with communities of microbes (bacteria and fungi) that play critical roles in plant development, nutrient acquisition and oxidative stress tolerance. The major share of plant microbiota is endophytes which inhabit plant tissues and help them in various capacities. In this article, we have reviewed what is presently known with regard to how endophytic microbes interact with plants to modulate root development, branching, root hair formation and their implications in overall plant development. Endophytic microbes link the interactions of plants, rhizospheric microbes and soil to promote nutrient solubilization and further vectoring these nutrients to the plant roots making the soil-plant-microbe continuum. Further, plant roots internalize microbes and oxidatively extract nutrients from microbes in the rhizophagy cycle. The oxidative interactions between endophytes and plants result in the acquisition of nutrients by plants and are also instrumental in oxidative stress tolerance of plants. It is evident that plants actively cultivate microbes internally, on surfaces and in soils to acquire nutrients, modulate development and improve health. Understanding this continuum could be of greater significance in connecting endophytes with the hidden half of the plant that can also be harnessed in applied terms to enhance nutrient acquisition through the development of favourable root system architecture for sustainable production under stress conditions.

Validation of a new approach for distinguishing anesthetized from awake state in patients using directed transfer function applied to raw EEG.

We test whether a measure based on the directed transfer function (DTF) calculated from short segments of electroencephalography (EEG) time-series can be used to monitor the state of the patients also during sevoflurane anesthesia as it can for patients undergoing propofol anesthesia. We collected and analyzed 25-channel EEG from 7 patients (3 females, ages 41-56 years) undergoing surgical anesthesia with sevoflurane, and quantified the sensor space directed connectivity for every 1-s epoch using DTF. The resulting connectivity parameters were compared to corresponding parameters from our previous study (n = 8, patients anesthetized with propofol and remifentanil, but otherwise using a similar protocol). Statistical comparisons between and within studies were done using permutation statistics, a data driven algorithm based on the DTF-parameters was employed to classify the epochs as coming from awake or anesthetized state. According to results of the permutation tests, DTF-parameter topographies were significantly different between the awake and anesthesia state at the group level. However, the topographies were not significantly different when comparing results computed from sevoflurane and propofol data, neither in the awake nor in anesthetized state. Optimizing the algorithm for simultaneously having high sensitivity and specificity in classification yielded an accuracy of 95.1% (SE = 0.96%), with sensitivity of 98.4% (SE = 0.80%) and specificity of 94.8% (SE = 0.10%). These findings indicate that the DTF changes in a similar manner when humans undergo general anesthesia caused by two distinct anesthetic agents with different molecular mechanisms of action.