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The thalamus has a key role in mediating cortical-subcortical interactions but is often neglected in neuroimaging studies, which mostly focus on changes in cortical structure and activity. One of the main reasons for the thalamus being overlooked is that the delineation of individual thalamic nuclei via neuroimaging remains controversial. Indeed, neuroimaging atlases vary substantially regarding which thalamic nuclei are included and how their delineations were established. Here, we review current and emerging methods for thalamic nuclei segmentation in neuroimaging data and consider the limitations of existing techniques in terms of their research and clinical applicability. We address these challenges by proposing a roadmap to improve thalamic nuclei segmentation in human neuroimaging and, in turn, harmonize research approaches and advance clinical applications. We believe that a collective effort is required to achieve this. We hope that this will ultimately lead to the thalamic nuclei being regarded as key brain regions in their own right and not (as often currently assumed) as simply a gateway between cortical and subcortical regions., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. Springer Nature Limited.)

Background: Thalamic nuclei facilitate a wide range of complex behaviors, emotions, and cognition and have been implicated in neuropsychiatric disorders including Alzheimer's disease (AD) and schizophrenia (SCZ). The aim of this work was to establish novel normative models of thalamic nuclear volumes and their laterality indices and investigate their changes in SCZ and AD., Methods: Volumes of bilateral whole thalami and 10 thalamic nuclei were generated from T1 magnetic resonance imaging data using a state-of-the-art novel segmentation method in healthy control participants (n = 2374) and participants with early mild cognitive impairment (n = 211), late mild cognitive impairment (n = 113), AD (n = 88), and SCZ (n = 168). Normative models for each nucleus were generated from healthy control participants while controlling for sex, intracranial volume, and site. Extreme z-score deviations (|z| > 1.96) and z-score distributions were compared across phenotypes. z Scores were associated with clinical descriptors., Results: Increased infranormal and decreased supranormal z scores were observed in SCZ and AD. z Score shifts representing reduced volumes were observed in most nuclei in SCZ and AD, with strong overlap in the bilateral pulvinar, medial dorsal, and centromedian nuclei. Shifts were larger in AD, with evidence of a left-sided preference in early mild cognitive impairment while a predilection for right thalamic nuclei was observed in SCZ. The right medial dorsal nucleus was associated with disorganized thought and daily auditory verbal hallucinations., Conclusions: In AD, thalamic nuclei are more severely and symmetrically affected, while in SCZ, the right thalamic nuclei are more affected. We highlight the right medial dorsal nucleus, which may mediate multiple symptoms of SCZ and is affected early in the disease course., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Ketamine is a rapid-acting antidepressant that also influences neural reactivity to affective stimuli. However, the effect of ketamine on behavioral affective reactivity is yet to be elucidated. The affect-modulated startle reflex paradigm (AMSR) allows examining the valence-specific aspects of behavioral affective reactivity. We hypothesized that ketamine alters the modulation of the startle reflex during processing of unpleasant and pleasant stimuli and weakens the resting-state functional connectivity (rsFC) within the modulatory pathway, namely between the centromedial nucleus of the amygdala and nucleus reticularis pontis caudalis. In a randomized, double-blind, placebo-controlled, cross-over study, thirty-two healthy male participants underwent ultra-high field resting-state functional magnetic resonance imaging at 7 T before and 24 h after placebo and S-ketamine infusions. Participants completed the AMSR task at baseline and one day after each infusion. In contrast to our hypothesis, ketamine infusion did not impact startle potentiation during processing of unpleasant stimuli but resulted in diminished startle attenuation during processing of pleasant stimuli. This diminishment significantly correlated with end-of-infusion plasma levels of ketamine and norketamine. Furthermore, ketamine induced a decrease in rsFC within the modulatory startle reflex pathway. The results of this first study on the effect of ketamine on the AMSR suggest that ketamine might attenuate the motivational significance of pleasant stimuli in healthy participants one day after infusion., (© 2023. Springer Nature Limited.)

The intralaminar nuclei of the thalamus play a pivotal role in awareness, conscious experience, arousal, sleep, vigilance, as well as in cognitive, sensory, and sexual processing. Nonetheless, in humans, little is known about the direct involvement of these nuclei in such multifaceted functions and their structural connections in the brain. Thus, examining the versatility of structural connectivity of the intralaminar nuclei with the rest of the brain seems reasonable. Herein, we attempt to show the direct structural connectivity of the intralaminar nuclei to diencephalic, mesencephalic, and cortical areas using probabilistic tracking of the diffusion data from the human connectome project. The intralaminar nuclei fiber distributions span a wide range of subcortical and cortical areas. Moreover, the central medial and parafascicular nucleus reveal similar connectivity to the temporal, visual, and frontal cortices with only slight variability. The central lateral nucleus displays a refined projection to the superior colliculus and fornix. The centromedian nucleus seems to be an essential component of the subcortical somatosensory system, as it mainly displays connectivity via the medial and superior cerebellar peduncle to the brainstem and the cerebellar lobules. The subparafascicular nucleus projects to the somatosensory processing areas. It is interesting to note that all intralaminar nuclei have connections to the brainstem. In brief, the structural connectivity of the intralaminar nuclei aligns with the structural core of various functional demands for arousal, emotion, cognition, sensory, vision, and motor processing. This study sheds light on our understanding of the structural connectivity of the intralaminar nuclei with cortical and subcortical structures, which is of great interest to a broader audience in clinical and neuroscience research., (© 2023. The Author(s).)

Although the thalamus is perceived as a passive relay station for almost all sensory signals, the function of individual thalamic nuclei remains unresolved. In the present study, we aimed to identify the sensorimotor nuclei of the thalamus in humans using task-based fMRI at a field strength of 9.4T by assessing the individual subject-specific sensorimotor BOLD response during a combined active motor (finger-tapping) and passive sensory (tactile-finger) stimulation. We demonstrate that both tasks increase BOLD signal response in the lateral nuclei group (VPL, VA, VLa, and VLp), and in the pulvinar nuclei group (PuA, PuM, and PuL). Finger-tapping stimuli evokes a stronger BOLD response compared to the tactile stimuli, and additionally engages the intralaminar nuclei group (CM and Pf). In addition, our results demonstrate reproducible thalamic nuclei activation during motor and tactile stimuli. This work provides important insight into understanding the function of individual thalamic nuclei in processing various input signals and corroborates the benefits of using ultra-high-field MR scanners for functional imaging of fine-scale deeply located brain structures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Charyasz, Heule, Molla, Erb, Kumar, Grodd, Scheffler and Bause.)

Valence tautomerism (VT) and spin crossover (SCO) are promising avenues for developing a range of molecular materials for sensing, memory, and optoelectronic applications. However, these phenomena arise only when specific metal-ligand combinations are employed. The underexplored combination of cobalt(II/III) paired with bis((aryl)imino)acenapthene (Ar-BIAN) ligands, which can exist as neutral Ar-BIAN 0 (L 0 ), monoanionic radical Ar-BIAN •- (L •- ), and dianionic Ar-BIAN 2- (L 2- ) forms, has potential to afford both VT and SCO. Aiming to develop a new family of switchable molecules, we systematically explored a dual-tuning approach by varying the redox state and aryl substituents in a series of homoleptic [Co(Ar-BIAN) 3 ] n + complexes (Ar = Ph, n = 2 ( 1 2+ ), 1 ( 1 + ), 0 ( 1 ); Ar = 3,5-CF 3 -Ph, n = 0 ( 2 ); Ar = 4-MeO-Ph, n = 2 ( 3 2+ ), 0 ( 3 )). As a prelude to synthetic and experimental studies, density functional theory (DFT) calculations were used to explore the structure and relative energies of the different electronic forms of each complex, comprising different cobalt oxidation and spin states and different ligand oxidation states. Except for compound 3 , DFT identified a HS-Co II -L 0 containing ground state for all complexes, precluding thermally induced SCO or VT. For 3 , calculations suggested a possible thermally accessible LS-Co III -(L •- ) 3 ⇌ HS-Co II -(L •- ) 2 (L 0 ) VT interconversion. Experimentally, structural and magnetic data reveal a HS-Co II -L 0 containing ground state for all six compounds in the solid state, including 3 , discounting thermally induced VT or SCO. In solution, electrochemical and spectroscopic analysis also indicate that all compounds exist as the HS-Co II -L 0 -containing electromer at 298 K. Intervalence charge transfer (IVCT) bands observed for neutral 1 , 2 , and 3 at room temperature suggest the mixed-valence HS-Co II -(L •- ) 2 (L 0 ) charge distribution. However, cooling 3 to 243 K in acetonitrile uniquely affords a substantial reduction in the intensity of this IVCT band, consistent with thermally induced VT interconversion to the LS-Co III -(L •- ) 3 ground state as predicted by DFT calculations. This study emphasizes the utility of computationally guided molecular design for complicated systems with redox activity at the metal and multiple ligands, thus opening new avenues for tuning electronic structure and developing new families of switchable molecules.

Almost all functional processing in the cortex strongly depends on thalamic interactions. However, in terms of functional interactions with the cerebral cortex, the human thalamus nuclei still partly constitute a terra incognita. Hence, for a deeper understanding of thalamic-cortical cooperation, it is essential to know how the different thalamic nuclei are associated with cortical networks. The present work examines network-specific connectivity and task-related topical mapping of cortical areas with the thalamus. The study finds that the relay and higher-order thalamic nuclei show an intertwined functional association with different cortical networks. In addition, the study indicates that relay-specific thalamic nuclei are not only involved with relay-specific behavior but also in higher-order functions. The study enriches our understanding of interactions between large-scale cortical networks and the thalamus, which may interest a broader audience in neuroscience and clinical research., (© 2022. The Author(s).)

Background: Chronic ulcers are defined as the breakdown of the epidermal and dermal tissue lasting for more than 6 weeks. There will be a lack of necessary growth factors in chronic non-healing ulcers. This study is aimed at accessing the efficacy of autologous platelet-rich fibrin in chronic non-healing ulcers., Aims and Objectives: To determine the efficacy of autologous platelet-rich fibrin in chronic non-healing ulcers and to compare the rate of healing in different ulcers based on aetiology., Methods: A hospital-based prospective study was conducted at the Department of Dermatology, Venereology, and Leprosy, at a tertiary care centre in Central Karnataka with 50 cases of chronic non-healing ulcers over 2 years. In each case baseline data including age and gender was collected and thorough general physical, local, and systemic examinations were done with the help of a predesigned proforma. PRF dressing was done weekly for 4 weeks with ulcer volume measured each time and improvement accessed., Results: In this study, the mean age of the study population was 43.56 ± 14.06 years, with 84% males. Good improvement in the volume of the ulcer was seen in 6 patients out of 50, moderate improvement was seen in 20 out of 50 patients and mild in the rest of the 24 patients. Improvement was more in the educated sector, more so in females and patients with trauma as the cause of ulcers without any comorbidities. Leprosy followed by diabetes was the main cause of chronic non-healing ulcers., Conclusions: This study shows that autologous platelet-rich fibrin therapy provides faster wound healing in chronic non-healing ulcers with no adverse events., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Dermatology.)

Integrating radical (open-shell) species into non-cryogenic nanodevices is key to unlocking the potential of molecular electronics. While many efforts have been devoted to this issue, in the absence of a chemical/electrochemical potential the open-shell character is generally lost in contact with the metallic electrodes. Herein, single-molecule devices incorporating a 6-oxo-verdazyl persistent radical have been fabricated using break-junction techniques. The open-shell character is retained at room temperature, and electrochemical gating permits in situ reduction to a closed-shell anionic state in a single-molecule transistor configuration. Furthermore, electronically driven rectification arises from bias-dependent alignment of the open-shell resonances. The integration of radical character, transistor-like switching, and rectification in a single molecular component paves the way to further studies of the electronic, magnetic, and thermoelectric properties of open-shell species., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Hypoxia is a common stressor in aquaculture systems, which causes severe physiological disturbances, ultimately leading to mortality or reduced productivity. Arginine, as a precursor of NO, has a role in enhancing oxygen delivery. Thus, an experiment was conducted to evaluate the effect of dietary arginine (Arg) in Cirrhinus mrigala exposed to hypoxia. The fish were fed with different levels of arginine for 60 days and exposed for 72 h to a sublethal level of hypoxia (0.50 ± 0.16 mg/L dissolved oxygen [DO]). The six treatment groups with three replicates were N0 (0% Arg + Normoxia), H0 (0% Arg + Hypoxia), N0.7 (0.70% Arg + Normoxia), H0.7 (0.70% Arg + Hypoxia), N1.4 (1.40% Arg + Normoxia), H1.4 (1.40% Arg + Hypoxia). Eighteen experimental units with twelve animals (5.8 ± 0.18 g) each were used for the trial.The results indicated that supplementation of arginine at 0.7 and 1.4% enhanced the hypoxia tolerance time, although the high dose (1.4%) did not yield any further increments. The exposure to hypoxia up-regulated Hypoxia Inducible Factor (HIF)-1α mRNA expression and supplementation of arginine significantly decreased hypoxia induced up-regulation of HIF at 1.4%. Arginine supplementation partially or completely normalised the hypoxia induced changes in the metabolic enzymes of C. mrigala. The fish exposed to hypoxic conditions exhibited significantly higher (P < 0.05) lipid peroxidation levels than those maintained under normoxic conditions, while arginine feeding significant in reducing lipid peroxidation. Antioxidant enzyme activities were significantly higher (P < 0.05) in hypoxia-exposed carp, indicating increased oxidative stress during the hypoxic exposure, that was improved in Arg-supplemented groups. However, arginine did not modulate erythrocyte countsalthough itreduced the erythrocyte fragility. We conclude arginine supplementation is effective in ameliorating hypoxia induced metabolic alterations and improving antioxidant defences in fish., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The thalamus (Th) and basal ganglia (BG) are central subcortical connectivity hubs of the human brain, whose functional anatomy is still under intense investigation. Nevertheless, both substructures contain a robust and reproducible functional anatomy. The quantitative susceptibility mapping (QSM) at ultra-high field may facilitate an improved characterization of the underlying functional anatomy in vivo . We acquired high-resolution QSM data at 9.4 Tesla in 21 subjects, and analyzed the thalamic and BG by using a prior defined functional parcellation. We found a more substantial contribution of paramagnetic susceptibility sources such as iron in the pallidum in contrast to the caudate, putamen, and Th in descending order. The diamagnetic susceptibility sources such as myelin and calcium revealed significant contributions in the Th parcels compared with the BG. This study presents a detailed nuclei-specific delineation of QSM-provided diamagnetic and paramagnetic susceptibility sources pronounced in the BG and the Th. We also found a reasonable interindividual variability as well as slight hemispheric differences. The results presented here contribute to the microstructural knowledge of the Th and the BG. In specific, the study illustrates QSM values (myelin, calcium, and iron) in functionally similar subregions of the Th and the BG., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kumar, Scheffler, Hagberg and Grodd.)

The thalamus is a vital communication hub in the center of the brain and consists of distinct nuclei critical for consciousness and higher-order cortical functions. Structural and functional thalamic alterations are involved in the pathogenesis of common brain disorders, yet the genetic architecture of the thalamus remains largely unknown. Here, using brain scans and genotype data from 30,114 individuals, we identify 55 lead single nucleotide polymorphisms (SNPs) within 42 genetic loci and 391 genes associated with volumes of the thalamus and its nuclei. In an independent validation sample (n = 5173) 53 out of the 55 lead SNPs of the discovery sample show the same effect direction (sign test, P = 8.6e-14). We map the genetic relationship between thalamic nuclei and 180 cerebral cortical areas and find overlapping genetic architectures consistent with thalamocortical connectivity. Pleiotropy analyses between thalamic volumes and ten psychiatric and neurological disorders reveal shared variants for all disorders. Together, these analyses identify genetic loci linked to thalamic nuclei and substantiate the emerging view of the thalamus having central roles in cortical functioning and common brain disorders.

Brain controllability properties are normally derived from the white matter fiber tracts in which the neural substrate of the actual energy consumption, namely the gray matter, has been widely ignored. Here, we study the relationship between gray matter volume of regions across the whole cortex and their respective control properties derived from the structural architecture of the white matter fiber tracts. The data suggests that the ability of white fiber tracts to exhibit control at specific nodes not only depends on the connection strength of the structural connectome but additionally depends on gray matter volume at the host nodes. Our data indicate that connectivity strength and gray matter volume interact with respect to the brain's control properties. Disentangling effects of the regional gray matter volume and connectivity strength, we found that frontal and sensory areas play crucial roles in controllability. Together these results suggest that structural and regional properties of the white matter and gray matter provide complementary information in studying the control properties of the intrinsic structural and functional architecture of the brain., (© 2020 Massachusetts Institute of Technology.)

The limbic system is a phylogenetically old, behaviorally defined system that serves as a center for emotions. It controls the expression of anger, fear, and joy and also influences sexual behavior, vegetative functions, and memory. The system comprises a collection of tel-, di-, and mesencephalic structures whose components have evolved and increased over time. Previous animal research indicates that the anterior nuclear group of the thalamus (ANT), as well as the habenula (Hb) and the adjacent mediodorsal nucleus (MD) each play a vital role in the limbic circuitry. Accordingly, diffusion imaging data of 730 subjects obtained from the Human Connectome Project and the masks of six nuclei (anterodorsal, anteromedial, anteroventral, lateral dorsal, Hb, and MD) served as seed regions for a direct probabilistic tracking to the rest of the brain using diffusion-weighted imaging. The results revealed that the ANT nuclei are part of the limbic and the memory system as they mainly connect via the mammillary tract, mammillary body, anterior commissure, fornix, and retrosplenial cortices to the hippocampus, amygdala, medio-temporal, orbito-frontal and occipital cortices. Furthermore, the ANT nuclei showed connections to the mesencephalon and brainstem to varying extents, a pattern rarely described in experimental findings. The habenula-usually defined as part of the epithalamus-was closely connected to the tectum opticum and seems to serve as a neuroanatomical hub between the visual and the limbic system, brainstem, and cerebellum. Finally, in contrast to experimental findings with tracer studies, directly determined connections of MD were mainly confined to the brainstem, while indirect MD fibers form a broad pathway connecting the hippocampus and medio-temporal areas with the mediofrontal cortex.

One of the major problems to be addressed in aquaculture is the prominence of antimicrobial resistance (AMR). The occurrence of bacterial infections in cultured fishes promotes the continuous use of antibiotics in aquaculture, which results in the selection of proliferated antibiotic-resistant bacteria and increases the possibility of transfer to the whole environment through horizontal gene transfer. Hence, the accurate cultivation-dependent and cultivation-independent detection methods are very much crucial for the immediate and proper management of this menace. Antimicrobial resistance determinants carrying mobile genetic transfer elements such as transposons, plasmids, integrons and gene cassettes need to be specifically analysed through molecular detection techniques. The susceptibility of microbes to antibiotics should be tested at regular intervals along with various biochemical assays and conjugation studies so as to determine the extent of spread of AMR. Advanced omic-based and bioinformatic tools can also be incorporated for understanding of genetic diversity. The present review focuses on different detection methods to unearth the complexity of AMR in aquaculture. This monitoring helps the authorities to curb the use of antibiotics, commencement of appropriate management measures and adequate substitute strategies in aquaculture. The long battle of AMR could be overcome by the sincere implementation of One Health approach. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of antibiotics and increased antimicrobial resistance (AMR) are of major concerns in aquaculture industry. This could result in global health risks through direct consumption of cultured fishes and dissemination of AMR to natural environment through horizontal gene transfer. Hence, timely detection of the antimicrobial-resistant pathogens and continuous monitoring programmes are inevitable. Advanced microbiological, molecular biological and omic-based tools can unravel the menace to a great extent. This will help the authorities to curb the use of antibiotics and implement appropriate management measures to overcome the threat., (© 2020 The Society for Applied Microbiology.)

The Indian major carp, mrigal (Cirrhinus mrigala), is a bottom-dwelling fish that can survive hypoxic episodes in its natural environment. We hypothesise that it can better survive hypoxic conditions by altering metabolic responses through GABA (Gamma-aminobutyric acid) supplementation. In the first experiment, the hypoxia tolerance time of the fishes was evaluated under extreme anoxic conditions after feeding with GABA, which showed that GABA had improved survival time under hypoxia. To study the response of dietary GABA in hypoxia-exposed fish, the branchial HIF-1α expression levels, serum thyroid hormone levels and hepatic metabolic responses were assessed in the subsequent experiment. The treatment groups were fed for 60 days with experimental diets containing 4 levels of GABA (0.00% G, 0.50% G, 0.75% G and 1.0%G) and were subjected to 72-h hypoxia exposure (0.5 ± 0.02 mg L -1 dissolved oxygen (DO)) whereas a control group was maintained under normoxic conditions (6.0 ± 0.21 mg L -1 DO). The five treatment groups with three replicates were C0 (0% G + normoxia), H0 (0% G + hypoxia), H0.5 (0.50% G + hypoxia), H0.75 (0.75% G + hypoxia) and H1.0 (1.00% G + hypoxia). The results indicated that GABA supplementation triggered downregulation of HIF 1 alpha expression. When compared with the control group, decreased thyroxine (T4) and triiodothyronine (T3) levels were observed in the GABA-fed hypoxic groups. However, TSH (thyroid stimulating hormone) level remained unchanged in all the treatments. The LDH (lactate dehydrogenase) level in hypoxia-exposed groups was decreased by GABA supplementation. Our study demonstrated that GABA supplementation restores acute hypoxia-induced HIF-1α expression, thyroid hormone levels and LDH activities. On the other hand, it enhanced the citrate synthase (CS) activities at 0.5-1.00%, which showed a sharp decline in hypoxia. Hypoxia caused increase in the serum metabolites such as glucose, lactate, cholesterol and triglycerides. However, GABA supplementation was partially effective in reducing glucose and lactate level while triglycerides and cholesterol values remained unchanged. Overall, our results suggested a potential role of GABA in suppressing metabolism during hypoxia exposure, which can increase the chances of survival of the species Cirrhinus mrigala during hypoxia.

Pattern classification and stratification approaches have increasingly been used in research on Autism Spectrum Disorder (ASD) over the last ten years with the goal of translation towards clinical applicability. Here, we present an extensive scoping literature review on those two approaches. We screened a total of 635 studies, of which 57 pattern classification and 19 stratification studies were included. We observed large variance across pattern classification studies in terms of predictive performance from about 60% to 98% accuracy, which is among other factors likely linked to sampling bias, different validation procedures across studies, the heterogeneity of ASD and differences in data quality. Stratification studies were less prevalent with only two studies reporting replications and just a few showing external validation. While some identified strata based on cognition and intelligence reappear across studies, biology as a stratification marker is clearly underexplored. In summary, mapping biological differences at the level of the individual with ASD is a major challenge for the field now. Conceptualizing those mappings and individual trajectories that lead to the diagnosis of ASD, will become a major challenge in the near future., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Whole-brain voxel-based morphometry (VBM) studies revealed patterns of patchy atrophy within the cerebellum of Friedreich's ataxia patients, missing clear clinico-anatomic correlations. Studies so far are lacking an appropriate registration to the infratentorial space. To circumvent these limitations, we applied a high-resolution atlas template of the human cerebellum and brainstem (SUIT template) to characterize regional cerebellar atrophy in Friedreich's ataxia (FRDA) on 3-T MRI data. We used a spatially unbiased voxel-based morphometry approach together with T2-based manual segmentation, T2 histogram analysis, and atlas generation of the dentate nuclei in a representative cohort of 18 FRDA patients and matched healthy controls. We demonstrate that the cerebellar volume in FRDA is generally not significantly different from healthy controls but mild lobular atrophy develops beyond normal aging. The medial parts of lobule VI, housing the somatotopic representation of tongue and lips, are the major site of this lobular atrophy, which possibly reflects speech impairment. Extended white matter affection correlates with disease severity across and beyond the cerebellar inflow and outflow tracts. The dentate nucleus, as a major site of cerebellar degeneration, shows a mean volume loss of about 30%. Remarkably, not the atrophy but the T2 signal decrease of the dentate nuclei highly correlates with disease duration and severity.

One of the principal goals in functional magnetic resonance imaging (fMRI) is the detection of local activation in the human brain. However, lack of statistical power and inflated false positive rates have recently been identified as major problems in this regard. Here, we propose a non-parametric and threshold-free framework called LISA to address this demand. It uses a non-linear filter for incorporating spatial context without sacrificing spatial precision. Multiple comparison correction is achieved by controlling the false discovery rate in the filtered maps. Compared to widely used other methods, it shows a boost in statistical power and allows to find small activation areas that have previously evaded detection. The spatial sensitivity of LISA makes it especially suitable for the analysis of high-resolution fMRI data acquired at ultrahigh field (≥7 Tesla).

Neurodevelopmental disorders, such as ASD and ADHD, affect males about three to four times more often than females. 16p11.2 hemideletion is a copy number variation that is highly associated with neurodevelopmental disorders. Previous work from our lab has shown that a mouse model of 16p11.2 hemideletion (del/+) exhibits male-specific behavioral phenotypes. We, therefore, aimed to investigate with magnetic resonance imaging (MRI), whether del/+ animals also exhibited a sex-specific neuroanatomical endophenotype. Using the Allen Mouse Brain Atlas, we analyzed the expression patterns of the 27 genes within the 16p11.2 region to identify which gene expression patterns spatially overlapped with brain structural changes. MRI was performed ex vivo and the resulting images were analyzed using Voxel-based morphometry for T1-weighted sequences and tract-based spatial statistics for diffusion-weighted images. In a subsequent step, all available in situ hybridization (ISH) maps of the genes involved in the 16p11.2 hemideletion were aligned to Waxholm space and clusters obtained by sex-specific group comparisons were analyzed to determine which gene(s) showed the highest expression in these regions. We found pronounced sex-specific changes in male animals with increased fractional anisotropy in medial fiber tracts, especially in those proximate to the striatum. Moreover, we were able to identify gene expression patterns spatially overlapping with male-specific structural changes that were associated with neurite outgrowth and the MAPK pathway. Of note, previous molecular studies have found convergent changes that point to a sex-specific dysregulation of MAPK signaling. This convergent evidence supports the idea that ISH maps can be used to meaningfully analyze imaging data sets.

Functional neuroimaging studies have led to understanding the brain as a collection of spatially segregated functional networks. It is thought that each of these networks is in turn composed of a set of distinct sub-regions that together support each network's function. Considering the sub-regions to be an essential part of the brain's functional architecture, several strategies have been put forward that aim at identifying the functional sub-units of the brain by means of functional parcellations. Current parcellation strategies typically employ a bottom-up strategy, creating a parcellation by clustering smaller units. We propose a novel top-down parcellation strategy, using time courses of instantaneous connectivity to subdivide an initial region of interest into sub-regions. We use split-half reproducibility to choose the optimal number of sub-regions. We apply our Instantaneous Connectivity Parcellation (ICP) strategy on high-quality resting-state FMRI data, and demonstrate the ability to generate parcellations for thalamus, entorhinal cortex, motor cortex, and subcortex including brainstem and striatum. We evaluate the subdivisions against available cytoarchitecture maps to show that our parcellation strategy recovers biologically valid subdivisions that adhere to known cytoarchitectural features., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In the present work, we used resting state-fMRI to investigate the functional anatomy of the thalamus at rest by applying an Independent Component Analysis to delineate thalamic substructures into stable and reproducible parcels for the left and right thalamus. We determined 15 functionally distinct thalamic parcels, which differed in laterality and size but exhibited a correspondence with 18 cytoarchitectonally defined nuclei. We characterized their structural connectivity in determining DWI based cortical fiber pathways and found selected projections to different cortical areas. In contrast, the functional connections of these parcels were not confined to certain cortical areas or lobes. We, finally evaluated cortical projections and found particular subcortical and cortical pattern for each parcel, which partly exhibited a correspondence with the thalamo-cortical connectivity maps of the mouse., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Rickettsial diseases are some of the most covert reemerging infections of the present times. They are generally incapacitating and notoriously difficult to diagnose; untreated cases can have fatality rates as high as 30%-35%, but when diagnosed properly, they are often easily treated but lack of definite diagnostic tools and the hazards of handling these microorganisms aggravate the difficulties of diagnosis and treatment., Competing Interests: There are no conflicts of interest. What is new? In cases of purpura fulminans, Rickettsial infections should be considered as an etiologyIn India, Scrub typhus and Indian Tick Typhus are most common type of Rickettsial infections.

In this Research, an effort has been done for the development of effervescent controlled release floating tablet (ECRFT) from solid dispersions (SDs) of diclofenac sodium (DS) for upsurge the solubility and dissolution rate. ECRFT of DS was prepared by using SDs of DS and its SDs prepared with PEG as carrier using thermal method (Simple fusion). SDs of DS were formulated in many ratio (1:1, 1:2, 1:3 and 1:4). Prepared SDs was optimized for its solubility, % drug content and % dissolution studies. Tablets were formulated by using optimized SDs products and all formulation was evaluated for various parameters. A clear rise in dissolution rate was detected with entirely SD, amid that the optimized SD (SD4) was considered for ECRFT. Among all the tablet formulations, its F3 formulation was better in all the terms of pre compression and post compression parameters. It had all the qualities of a good ECRFT, based on this F3 formulation was selected as the best formulation. Data of in vitro release was fitted in several kinetics models to explain release mechanism. The F3 formulation shows zero order release. From this study we can concluded that ECRFT containing SDs of DS can be successfully used for achieving better therapeutic objective.

During the synthesis of ezetimibe, two process related impurities were detected were HPLC analysis at levels ranging from 0.05 to 0.8%. These two impurities were isolated by column chromatography and co-injected with ezetimibe sample to confirm the retention times in HPLC. These two impurities were characterized as 2-(4-hydroxybenzyl)-N,5-bis(4-fluorophenyl) pentanamide (impurity-I) and 1-(4-fluorophenyl)-3(3-(4-fluorophenyl)propyl)-4-(4-hydroxyphenyl)azetidin-2-one (impurity-II). Isolation, structural elucidation of these impurities by spectral data ((1)H NMR, (13)C NMR, MS and IR) and probable mechanism of their formation have been discussed., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Unlabelled: Korean kimchi is known for its myriad of lactic acid bacteria (LAB) with diverse bioactive compounds. This study was undertaken to isolate an efficient antifungal LAB strain among the isolated kimchi LABs. One thousand and four hundred LABs isolated from different kimchi samples were initially screened against Aspergillus niger. The strain exhibiting the highest antifungal activity was identified as Lactobacillus plantarum YML007 by 16S rRNA sequencing and biochemical assays using API 50 CHL kit. Lact. plantarum YML007 was further screened against Aspergillus oryzae, Aspergillus flavus, Fusarium oxysporum and other pathogenic bacteria. The morphological changes during the inhibition were assessed by scanning electron microscopy. Preliminary studies on the antifungal compound demonstrated its proteinaceous nature with a molecular weight of 1256·617 Da, analysed by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF). The biopreservative activity of Lact. plantarum YML007 was evaluated using dried soybeans. Spores of A. niger were observed in the negative control after 15 days of incubation. However, fungal growth was not observed in the soybeans treated with fivefold concentrated cell-free supernatant of Lact. plantarum YML007. The broad activity of Lact. plantarum YML007 against various food spoilage moulds and bacteria suggests its scope as a food preservative., Significance and Impact of the Study: After screening 1400 kimchi bacterial isolates, strain Lactobacillus plantarum YML007 was selected with strong antifungal activity against various foodborne pathogens. From the preliminary studies, it was found that the bioactive compound is a low molecular weight novel protein of 1256·617 Da. Biopreservative potential of Lact. plantarum YML007 was demonstrated on soybean grains, and the results point out YML007 as a potent biopreservative having broad antimicrobial activity against various foodborne pathogens., (© 2013 The Society for Applied Microbiology.)

Aim:   The aims of the study were to isolate anti-H9N2 bacteria from Korean Kimchi isolates and to evaluate its performance in cell line, egg and in specific pathogen-free (SPF) chickens., Methods and Results:   Using Madin-Darby canine kidney (MDCK) cell line, 220 bacterial isolates were screened and the isolate YML003 was selected having pronounced antiviral activity against H9N2 virus. This isolate was identified as Leuconostoc mesenteroides by 16S rRNA gene sequencing. Anti-H9N2 activity of the strain was also evaluated by hemagglutination assay. Leuconostoc mesenteroides YML003 was assessed for its survival in gastric juice and 5% bile acid and the antibiotic susceptibility. Both live and heat-killed cells were selected for in vivo chicken feeding experiment. Body weight, immune index, serobiochemical parameters and splenic IFN-γ production were assessed during selected intervals. Viral population in the trachea and cloacae were calculated by quantitative real-time reverse transcriptase PCR (qRT-PCR)., Conclusions:   Leuconostoc mesenteroides YML003 exhibited anti-H9N2 activity both in in vitro cell line as well as in vivo SPF chickens., Significance and Impact of the Study:   This is a primary report on the anti-H9N2 activity by a Leuconostoc strain. Amid the increasing reports of avian influenza virus occurrence resulting in severe losses to the poultry industry, prophylactic administration of such probiotic strains are highly significant., (© 2012 The Authors. Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.)

The biological control efficacy of a greenhouse soil bacterial mixture of Lactobacillus farraginis, Bacillus cereus, and Bacillus thuringiensis strains with antinematode activity was evaluated against the root-knot nematode Meloidogyne incognita. Two control groups planted in soil drenched with sterile distilled water or treated with the broadspectrum carbamate pesticide carbofuran were used for comparison. The results suggest that the bacterial mixture is effective as a biocontrol agent against the root-knot nematode.

Background: Phrynoderma is a type of follicular hyperkeratosis. Various nutritional deficiency disorders have been implicated in the etiology of phrynoderma., Aim: To determine clinical features of phrynoderma and its association with nutritional deficiency signs., Materials and Methods: A cross-sectional descriptive study of 125 consecutive patients with phrynoderma attending the outpatient department (OPD) of dermatology was conducted in a tertiary care hospital. In all patients, a detailed history was taken and cutaneous examination findings such as distribution, sites of involvement, morphology of the lesions, and signs of nutritional deficiencies were noted., Results: The proportion of patients with phrynoderma attending the OPD was 0.51%. There were 79 males and 46 females. Age of the patients was in the range of 3-26 years with a mean of 10 ± 4.3 years. The lesions were asymptomatic in 114 (91.2%) patients. The distribution of lesions was bilateral and symmetrical in 89 (71.2%) patients. The disease was localized (elbows, knees, extensor extremities, and/or buttocks) in 106 (84.8%) patients. The site of onset was elbows in 106 (84.8%) patients. The lesions were discrete, keratotic, follicular, pigmented or skin colored, acuminate papules in all patients. Signs of vitamin A and vitamin B-complex deficiency were present in 3.2% and 9.6% patients, respectively. Epidermal hyperkeratosis, follicular hyperkeratosis, and follicular plugging were present in the entire biopsy specimen., Conclusion: Phrynoderma is a disorder with distinctive clinical features and can be considered as a multifactorial disease involving multiple nutrients, local factors like pressure and friction, and environmental factors in the setting of increased nutritional demand.

A new degradant of sultamicillin drug substance was found during the gradient reverse phase HPLC analysis of stability storage samples. The level of this degradant impurity was observed up to 1.0%. The impurity (formaldehyde adduct with 5-oxo-4-phenylimidazolidin-1-yl moiety) was identified by LC/MS and was characterized by ((1)H NMR, (13)C NMR, 2D-NMR ((1)H-(1)H COSY, NOESY, HSQC and HMBC), LC/MS/MS, MS/TOF, elemental analysis and IR. This impurity was prepared by isolation and co-injected into HPLC system to confirm the retention time., (Copyright © 2010 Elsevier B.V. All rights reserved.)

A simple and sensitive ion chromatography method has been developed for the simultaneous assay of ibandronate sodium drug substance and the determination of its impurities. The separation was achieved on Allsep™ anion column 150 mm × 4.6 mm, 7 μm particle diameter. The mobile phase consisted of 1% (v/v) aqueous formic acid and acetone 98:2% (v/v); flow rate 1.0 ml min(-1) at ambient temperature. The analytes were monitored by conductometric detector. The drug substance was subjected to stress conditions of hydrolysis, oxidation, photolytic, thermal and humidity degradation. Considerable degradation was achieved only under oxidative conditions. Mass balance was demonstrated in all stress conditions. The method was validated for specificity, precision, linearity, solution stability and accuracy. The limits of detection (LOD) and limits of quantification (LOQ) for impurities were in the range of 0.36-0.80 μg ml(-1) and 1.00-2.40 μg ml(-1), respectively. For ibandronate LOD was 38 μg ml(-1) and LOQ was 113 μg ml(-1). The average recoveries for impurities and ibandronate were in the range of 99.0-103.1% and the method can be successfully applied for the routine analysis of ibandronate sodium drug substance., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Introduction: The estimation of the age of a person has been an archaic exercise, and since decades even dentists have contributed to this science with several methods through radiography. The tooth with its developmental stages provides us with a non-invasive modality to determine the age of the person., Aim: To evaluate the reliability of age estimation using Demirjian's 8 teeth method following the French maturity scores and India specific formula., Materials and Methods: The study was conducted on 121 archived digital orthopantamographs which were predominantly pre-treatment orthodontic radiographs from patients without any obvious developmental anomalies. The radiographs were divided into two gender specific groups and further sub-divided into two smaller groups of 7-16 years and 16.1-23 years. The radiographs were evaluated as per Demirjian's criteria and age was calculated using the formula developed for the Indian population., Results: The results showed that the mean absolute error for the study sample was 1.18 years; in 57.9% of cases the error rate was within ±1 year. The mean absolute error in males (7-16 years) was 1.2 years; in males (16.1-23 years) was 1.3 years; in females (7-16 years) was 0.95 years and in females (16.1-23 years) was 1.16 years., Conclusion: The age estimation using this method narrows down the error rate to just over one year making this method reliable. However the inclusion of third molar increases the error rates in the older individuals within the sample.

A new unknown impurity of cefoxitin formed during a gradient reverse phase high performance liquid chromatography (HPLC) analysis of stress stability samples of the drug substance cefoxitin, and the level of this impurity was found at up to 0.9%. This impurity was identified by LC-MS and characterized by (1H NMR, 13C NMR, LC/MS/MS, elemental analysis and FT-IR). Based on the spectral data, the impurity was named as, 3-[[(2R,3S)-[3-methoxy-3-N-[2-(thiophen-2-yl)acetamido]]-4-oxoazetidin-2-ylthio]-2-[(carbamoyloxy)methyl]]-acrylic acid. The structure of this impurity was also established unambiguously, prepared by isolation and co-injected into HPLC to confirm the retention time. To the best of our knowledge, this impurity has not been reported elsewhere. Structural elucidation of the impurity by spectral data is discussed in detail.

The present study relates to a new capillary electrophoresis method for the determination of N-methylpyrrolidine, an impurity considered to be toxic and also potential degradation impurity in cefepime hydrochloride drug substance. The newly developed capillary electrophoresis method for determining the content of N-methylpyrrolidine in cefepime for injection has been validated as per International Conference on Harmonization (ICH) guidelines to prove the selectivity, sensitivity, suitability, robustness, and ruggedness of the method. This simple, efficient, and rapid methodology may be used by pharmaceutical industry for routine analysis as well as during stability studies. The newly developed capillary electrophoresis method to determine the content of N-methylpyrrolidine in cefepime for injection requires 10 min for data acquisition, and uses an indirect UV photometry method to detect the analyte signal at 240 nm against the reference signal at 210 nm. The electrophoretic system is optimized to get stable base line, higher signal to noise ratio and peaks with narrow peak width. The method employs bare fused silica capillary with extended light path, effective length of capillary is 56 cm and inner diameter of capillary is 50 μm, 5 mmole of imidazole buffer adjusted to pH 5.1 with 3 molar acetic acid solution is used as background electrolyte. The sample is introduced in hydrodynamic mode employing pressure of 50 mbar for 5 s, and the desired separation is achieved with constant applied voltage of 25 kV at ambient temperature (~25°C).

Introduction: Advanced age, deep myoinvasion, whole cavity or lower uterine segment tumors, poor differentiation, and lymphovascular space invasion are known to increase recurrence risk and adversely affect survival in stage I endometrioid adenocarcinoma of the uterus., Objectives: To ascertain survival rates, failure patterns, and salvageability and to correlate adverse histopathologic effects to recurrences in these patients., Methods: Data of 162 patients with surgical stage I endometrioid adenocarcinoma of the uterus with an increased risk of recurrence were reviewed from the year 1997 to 2008 at KK Gynaecological Cancer Centre, Singapore. Each patient underwent surgical staging and histopathologic evaluation and received high-dose rate vaginal vault brachytherapy. The data of all patients were discussed in a multidisciplinary meeting., Results: The mean patient age was 58.9 years. Most patients (54.3%) had surgical stage IC endometrioid adenocarcinoma, whereas the rest had stage IB. Grade 2 tumors were seen in 53.7% of the patients and grade 3 in 21.61%. The mean follow-up duration was 52.9 months, with a maximum of 11.5 years. Five- and 10-year survival rates were 94% and 89%, respectively. There were 9 recurrences (5.56%). Stage IC had 77.78% recurrences, whereas stage IB had 22.22%, the median time being 19 months. The initial 3 years had 77.78% relapses. There was no recurrence in grade 3 tumors, with a 100% 5-year survival rate for stage IC grade 3. Age, lymphovascular space invasion, and tumor volume and location were not significant parameters in surgical stage I endometrioid adenocarcinoma patients who failed. One patient had isolated pelvic failure, whereas 5 had a pure distant relapse. Three patients failed at both locoregional and distant sites. Vault recurrence coupled with distant metastasis occurred in 1 patient. Three patients (33.33%) with recurrences, all with limited relapse sites, were salvaged, with a mean survival of 71.33 months. The median survival for recurrent endometrial cancer was 5 years., Conclusions: This treatment has excellent survival rates with acceptable morbidity, and recurrence is mostly distant.

Recirculation aquaculture systems (RAS) depend on nitrifying biofilters for the maintenance of water quality, increased biosecurity and environmental sustainability. To satisfy these requirements a packed bed bioreactor (PBBR) activated with indigenous nitrifying bacterial consortia has been developed and commercialized for operation under different salinities for instant nitrification in shrimp and prawn hatchery systems. In the present study the nitrification efficiency of the bioreactor was tested in a laboratory level recirculating aquaculture system for the rearing of Penaeus monodon for a period of two months under higher feeding rates and no water exchange. Rapid setting up of nitrification was observed during the operation, as the volumetric total ammonia nitrogen removal rates (VTR) increased with total ammonia nitrogen (TAN) production in the system. The average Volumetric TAN Removal Rates (VTR) at the feeding rate of 160 g/day from 54-60th days of culture was 0.1533+/-0.0045 kg TAN/m(3)/day. The regression between VTR and TAN explained 86% variability in VTR (P<0.001). The laboratory level RAS demonstrated here showed high performance both in terms of shrimp biomass yield and nitrification and environmental quality maintenance. Fluorescent in-situ Hybridization analysis of the reactor biofilm ensured the presence of autotrophic nitrifier groups such as Nitrosococcus mobilis lineage, Nitrobacter spp and phylum Nitrospira, the constituent members present in the original consortia used for activating the reactors. This showed the stability of the consortia on long term operation.