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Frontiers in Neurology 2022Psychogenic Non-Epileptic Seizures (PNES) are a misunderstood and disabling pathology, characterized by a paroxysmal occurrence of clinical signs without the epileptic...
Psychogenic Non-Epileptic Seizures (PNES) are a misunderstood and disabling pathology, characterized by a paroxysmal occurrence of clinical signs without the epileptic activity. Resting-state functional MRI (fMRI) studies in patients with PNES have shown abnormal functional connectivity of the resting-state networks, especially in the limbic and motor systems, and in the precuneus. However, the transient nature of PNES episodes prevents us from elucidating the underlying mechanisms of seizures. Here, we report the case of a patient who presented an atonic episode of PNES during a 3T fMRI session. The patient is a 23-year-old woman, suffering from post-traumatic stress disorder, with no neurological comorbidities. The preprocessing of the fMRI images involved realignment, co-registration, segmentation, normalization, denoising (PhysIO toolbox), and smoothing. The time boundary of the seizure was defined according to the patient's reports, and the seizure period was contrasted with the resting state period before the seizure. A whole-brain analysis showed significant activations (left inferior temporal gyrus, left temporo-occipital junction) and deactivations (right precuneus, right superior parietal lobule, right postcentral gyrus, bilateral lingual gyri, inferior occipital gyri, and cerebellar lobules; right insula in a sub-thresholded analysis). Activations and deactivations occurred in four cerebral networks: emotional processing, agency, self-perception, and dissociation. To our knowledge, this report is the first published case of functional MRI during PNES. These results could confirm the emotional and dissociative hypothesis of the physiopathology of PNES and highlight future targets for neuromodulation.
PubMed: 35265026
DOI: 10.3389/fneur.2022.803145 -
Nature Metabolism Jan 2021The mammalian liver is a central hub for systemic metabolic homeostasis. Liver tissue is spatially structured, with hepatocytes operating in repeating lobules, and...
The mammalian liver is a central hub for systemic metabolic homeostasis. Liver tissue is spatially structured, with hepatocytes operating in repeating lobules, and sub-lobule zones performing distinct functions. The liver is also subject to extensive temporal regulation, orchestrated by the interplay of the circadian clock, systemic signals and feeding rhythms. However, liver zonation has previously been analysed as a static phenomenon, and liver chronobiology has been analysed at tissue-level resolution. Here, we use single-cell RNA-seq to investigate the interplay between gene regulation in space and time. Using mixed-effect models of messenger RNA expression and smFISH validations, we find that many genes in the liver are both zonated and rhythmic, and most of them show multiplicative space-time effects. Such dually regulated genes cover not only key hepatic functions such as lipid, carbohydrate and amino acid metabolism, but also previously unassociated processes involving protein chaperones. Our data also suggest that rhythmic and localized expression of Wnt targets could be explained by rhythmically expressed Wnt ligands from non-parenchymal cells near the central vein. Core circadian clock genes are expressed in a non-zonated manner, indicating that the liver clock is robust to zonation. Together, our scRNA-seq analysis reveals how liver function is compartmentalized spatio-temporally at the sub-lobular scale.
Topics: Algorithms; Amino Acids; Animals; Carbohydrate Metabolism; Circadian Clocks; Gene Expression; Gene Expression Profiling; Hepatocytes; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Molecular Chaperones; Period Circadian Proteins; Periodicity; RNA, Messenger; Wnt Signaling Pathway
PubMed: 33432202
DOI: 10.1038/s42255-020-00323-1 -
Breast Cancer Research and Treatment Feb 2018While the role of natural killer (NK) cells in breast cancer therapy has been investigated, little information is known about NK cell function and presence in...
PURPOSE
While the role of natural killer (NK) cells in breast cancer therapy has been investigated, little information is known about NK cell function and presence in nonmalignant and premalignant breast tissue. Here, we investigate and quantify NK cell marker CD56 and activating ligand MICA in breast tissue with benign breast disease.
METHODS
Serial tissue sections from 88 subjects, 44 with benign breast disease (BBD) who remained cancer-free, and 44 with BBD who later developed cancer, were stained with H&E, anti-MICA, and anti-CD56. Up to ten representative lobules were identified on each section. Using digital image analysis, MICA and CD56 densities were determined for each lobule, reported as percent of pixels in the lobule that registered as stained by each antibody. Analyses were performed on a per-subject and per-lobule basis.
RESULTS
Per-subject multivariate analyses showed associations of CD56 and MICA with age: CD56 was increased in older subjects (p = 0.03), while MICA was increased in younger subjects (p = 0.005). Per-lobule analyses showed that CD56 and MICA levels were both decreased in lobules with fibrocystic change, with median levels of CD56 and MICA staining, respectively, at 0.31 and 7.0% in fibrocystic lobules compared to 0.76 and 12.2% in lobules without fibrocystic change (p < 0.001 for each). Among fibrocystic lobules, proliferative/atypical lobules showed significantly lower expression compared to nonproliferative lobules for MICA (p = 0.02) but not for CD56 (p = 0.80).
CONCLUSION
Levels of CD56+ NK cells and activating ligand MICA were decreased in breast lobules with fibrocystic change, and MICA levels showed a significant stepwise decrease with increasing histopathologic abnormality. MICA levels were also significantly decreased in older subjects, who generally have higher risk of developing cancer. These findings advance a model in which MICA promotes cytotoxic activity in CD56+ NK cells to protect against tumorigenesis in breast lobules, and suggest further research is warranted.
Topics: Adult; Aged; Breast; Breast Neoplasms; CD56 Antigen; Female; Histocompatibility Antigens Class I; Humans; Hyperplasia; Killer Cells, Natural; Male; Middle Aged; Neoplasms; Precancerous Conditions
PubMed: 29090365
DOI: 10.1007/s10549-017-4558-0 -
Veterinary Sciences Nov 2022The interdigital gland is a specialized skin gland located between the digits of Artiodactyla (i.e., even-toed ungulates). Its secretion participates in semiochemical...
The interdigital gland is a specialized skin gland located between the digits of Artiodactyla (i.e., even-toed ungulates). Its secretion participates in semiochemical communication, and protects from ultraviolet radiation as well as fungal and bacterial infections of the feet. The present study aimed at finding if there are male-female differences in the anatomy, morphology, and volatile compounds of the interdigital gland of the South Indian breed of Vembur sheep. A total of 24 sheep (12 each of male and female) were spotted at the slaughterhouse and the interdigital gland was removed for examination. The anatomical examination revealed it to resemble a tobacco pipe and to consist of a body, flexure, and excretory duct with an external orifice located at the cleft of the digits. Morphometrically, the interdigital glands differed between males and females. The gland possesses a distinct fibrous capsule, epidermis, and dermis. The fibrous capsule contains several parallel bundles of collagen fibers, nerve fibers, and blood vessels, etc. The epidermis consists of keratinized squamous epithelium formed of stratum basale, stratum granulosum and stratum spinosum. The dermis consists of hair follicles, nerve plexuses, arrector pili muscles, and apocrine and sebaceous glandular lobules. The latter, lined by a simple cuboidal epithelium, are arranged in clusters of acini in the upper portion of the dermis. The apocrine secretory lobules, made up of parenchymal cells, are found in the lower portion of the dermis. The density and diameter of the apocrine and sebaceous secretory lobules were significantly higher in the males than females. Scanning electron microscopic (SEM) analysis confirmed the apocrine and sebaceous secretory components. Twenty-three major compounds were identified in the interdigital gland postings of male and female sheep, among which butanoic acid, 2-methylpropanoic acid, 1-heptanol and octadecanoic acid were present only in the male glandular post, whereas octane, 7-hexyl-tridecane, tetradecane, heptadecane and decanoic acid were present only in the female glandular post. Tetradecanol, tetradecanoic acid and hexadecanol peaks, reportedly antibacterial compounds in pronghorn antelopes, were highly prominent in both male and female sheep. Thus, the interdigital gland of Vembur sheep has two major secretory lobules, namely, sebaceous and apocrine, larger in males than females, which secrete a variety chemical compounds that may serve as chemical communication systems and protect the sheep from foot-borne diseases.
PubMed: 36423097
DOI: 10.3390/vetsci9110647 -
Temporal Invariance in SCA6 Is Related to Smaller Cerebellar Lobule VI and Greater Disease Severity.The Journal of Neuroscience : the... Feb 2020Regulating muscle force and timing are fundamental for accurate motor performance. In spinocerebellar ataxia type 6 (SCA6), there is evidence that individuals have...
Regulating muscle force and timing are fundamental for accurate motor performance. In spinocerebellar ataxia type 6 (SCA6), there is evidence that individuals have greater force dysmetria but display better temporal accuracy during fast goal directed contractions. Here, we test whether greater temporal accuracy occurs in all individuals with SCA6, and can be explained by lesser temporal variability. Further we examine whether it is linked to disease severity and specific degenerative changes in the cerebellum. Nineteen human participants with SCA6 (13 woman) and 18 healthy controls performed fast goal-directed ankle dorsiflexion contractions aiming at a spatiotemporal target. We quantified the endpoint control of these contractions, gray matter (GM) integrity of the cerebellum, and disease severity using the International Cooperative Ataxia Rating Scale (ICARS). SCA6 individuals exhibited lower temporal endpoint error and variability than the healthy controls ( = 0.008). Statistically, SCA6 clustered into two distinct groups for temporal variability. A group with low temporal variability ranging from 10 to 19% (SCA6a) and a group with temporal variability similar to healthy controls (SCA6b; 19-40%).SCA6a exhibited greater disease severity than SCA6b, as assessed with ICARS ( < 0.001). Lower temporal variability, which was not associated with disease duration ( = 0.1, > 0.2), did correlate with both greater ICARS ( = 0.3) and reduced GM volume in cerebellar lobule VI ( = 0.35). Other cerebellar lobules did not relate to temporal variability. We provide new evidence that a subset of SCA6 with greater loss of GM in cerebellum lobule VI exhibit temporal invariance and more severe ataxia than other SCA6 individuals. Variability is an inherent feature of voluntary movement, and traditionally more variability in the targeted output infers impaired performance. For example, cerebellar patients present exacerbated temporal variability during multijoint movements, which is thought to contribute to their motor deficits. In the current work, we show that in a subgroup of spinocerebellar ataxia type 6 individuals, temporal variability is lower than that of healthy controls when performing single-joint fast-goal directed movements. This invariance related to exacerbated atrophy of lobule VI of the cerebellum and exacerbated disease severity. The relation between invariance and disease severity suggests that pathological motor variability can manifest not only as an exacerbation but also as a reduction relative to healthy controls.
Topics: Aged; Atrophy; Cerebellum; Female; Gray Matter; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Severity of Illness Index; Spinocerebellar Ataxias
PubMed: 31941666
DOI: 10.1523/JNEUROSCI.1532-19.2019 -
PloS One 2015Mal de debarquement syndrome (MdDS) is a disorder of chronic self-motion perception that occurs though entrainment to rhythmic background motion, such as from sea...
BACKGROUND
Mal de debarquement syndrome (MdDS) is a disorder of chronic self-motion perception that occurs though entrainment to rhythmic background motion, such as from sea voyage, and involves the perception of low-frequency rocking that can last for months or years. The neural basis of this persistent sensory perception abnormality is not well understood.
METHODS
We investigated grey matter volume differences underlying persistent MdDS by performing voxel-based morphometry on whole brain and pre-specified ROIs in 28 individuals with MdDS and comparing them to 18 age, sex, and handedness matched controls.
RESULTS
MdDS participants exhibited greater grey matter volume in the left inferior parietal lobule, right inferior occipital gyrus (area V3v), right temporal pole, bilateral cerebellar hemispheric lobules VIII/IX and left lobule VIIa/VIIb. Grey matter volumes were lower in bilateral inferior frontal, orbitofrontal, pregenual anterior cingulate cortex (pgACC) and left superior medial gyri (t = 3.0, p<0.005uncorr). In ROI analyses, there were no volume differences in the middle occipital gyrus (region of V5/MT) or parietal operculum 2 (region of the parietoinsular vestibular cortex). Illness duration was positively related to grey matter volume in bilateral inferior frontal gyrus/anterior insula (IFG/AI), right posterior insula, superior parietal lobule, left middle occipital gyrus (V5/MT), bilateral postcentral gyrus, anterior cerebellum, and left cerebellar hemisphere and vermian lobule IX. In contrast, illness duration was negatively related to volume in pgACC, posterior middle cingulate gyrus (MCC), left middle frontal gyrus (dorsolateral prefrontal cortex-DLPFC), and right cerebellar hemispheric lobule VIIIb (t = 3.0, p<0.005uncorr). The most significant differences were decreased volume in the pgACC and increased volume in the left IFG/AI with longer illness duration (qFDRcorr <0.05). Concurrent medication use did not correlate with these findings or have a relationship with duration of illness. MdDS participants showed positive correlations between grey matter volume in pgACC and bilateral cerebellar lobules VIII/IX, which was not seen in controls.
CONCLUSIONS
Individuals with MdDS show brain volume differences from healthy controls as well as duration of illness dependent volume changes in (a) visual-vestibular processing areas (IPL, SPL, V3, V5/MT), (b) default mode network structures (cerebellar IX, IPL, ACC), (c) salience network structures (ACC and IFG/AI) (d) somatosensory network structures (postcentral gyrus, MCC, anterior cerebellum, cerebellar lobule VIII), and (e) a structure within the central executive network (DLPFC). The identification of these associations may enhance future investigations into how exposure to oscillating environments can modulate brain function and affect motion perception as well cognitive and affective control.
Topics: Adult; Benzodiazepines; Brain; Brain Mapping; Case-Control Studies; Cerebellum; Contrast Media; Female; Frontal Lobe; Functional Laterality; Gray Matter; Gyrus Cinguli; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Motion Sickness; Neurons; Oscillometry; Parietal Lobe; Regression Analysis; Selective Serotonin Reuptake Inhibitors; Travel; Travel-Related Illness
PubMed: 26252893
DOI: 10.1371/journal.pone.0135021 -
Plastic and Reconstructive Surgery.... Jan 2016Ear lobule ptosis and deflation are characteristics of facial aging. A rhytidectomy without rejuvenation of a deflated ear lobule may fail to address all aspects of...
BACKGROUND
Ear lobule ptosis and deflation are characteristics of facial aging. A rhytidectomy without rejuvenation of a deflated ear lobule may fail to address all aspects of facial aging. Fillers have been used to treat ear lobule deflation; however, autologous fat transfer has never been utilized for ear lobule rejuvenation. This investigation studies the success of autologous fat transfer to the ear lobule as part of volume augmentation rhytidectomy.
METHODS
A retrospective review of patients who underwent rhytidectomy between 2000 and 2014 by a single surgeon was performed. Patients between 2000 and 2004 who did not receive autologous fat transfer served as controls (group A). Patients between 2010 and 2014 who received autologous fat transfer to the ear lobule formed the treatment group (group B). Three independent observers reviewed preoperative and postoperative photographs for both groups at 1 year postoperatively. The following ear lobule volume grading scale was applied to numerically assess the patients: concave = 0, flat = 1, convex = 2, and round = 3.
RESULTS
Groups A and B each consisted of 65 consecutive patients (130 ears). In group A, the mean preoperative ear lobule grading score was 1.20, and the mean postoperative score was 1.22 (mean difference, 0.02; P = 0.42). In group B, the mean preoperative ear lobule grading score was 0.98, and the mean postoperative score was 2.00 (mean difference, 1.02; P < 0.0001).
CONCLUSION
In patients receiving autologous fat transfer to the ear lobule during rhytidectomy, there was a significant change from a deflated ear lobule preoperatively to a more voluminous lobule at 1 year postoperatively.
PubMed: 27104096
DOI: 10.1097/GOX.0000000000000476 -
Human Brain Mapping Nov 2023Brain imaging has significantly contributed to our understanding of the cerebellum being involved in recovery after non-cerebellar stroke. Due to its connections with...
Brain imaging has significantly contributed to our understanding of the cerebellum being involved in recovery after non-cerebellar stroke. Due to its connections with supratentorial brain networks, acute stroke can alter the function and structure of the contralesional cerebellum, known as crossed cerebellar diaschisis (CCD). Data on the spatially precise distribution of structural CCD and their implications for persistent deficits after stroke are notably limited. In this cross-sectional study, structural MRI and clinical data were analyzed from 32 chronic stroke patients, at least 6 months after the event. We quantified lobule-specific contralesional atrophy, as a surrogate of structural CCD, in patients and healthy controls. Volumetric data were integrated with clinical scores of disability and motor deficits. Diaschisis-outcome models were adjusted for the covariables age, lesion volume, and damage to the corticospinal tract. We found that structural CCD was evident for the whole cerebellum, and particularly for lobules V and VI. Lobule VI diaschisis was significantly correlated with clinical scores, that is, volume reductions in contralesional lobule VI were associated with higher levels of disability and motor deficits. Lobule V and the whole cerebellum did not show similar diaschisis-outcome relationships across the spectrum of the clinical scores. These results provide novel insights into stroke-related cerebellar plasticity and might thereby promote lobule VI as a key area prone to structural CCD and potentially involved in recovery and residual motor functioning.
Topics: Humans; Cross-Sectional Studies; Diaschisis; Stroke; Cerebellum; Magnetic Resonance Imaging; Brain Damage, Chronic; Cerebrovascular Circulation
PubMed: 37471691
DOI: 10.1002/hbm.26434 -
Brain Structure & Function Mar 2017Spinocerebellar ataxia type 6 (SCA6) is a genetic disease that causes degeneration of Purkinje cells, and recent evidence points to degeneration of Betz cells in the...
Spinocerebellar ataxia type 6 (SCA6) is a genetic disease that causes degeneration of Purkinje cells, and recent evidence points to degeneration of Betz cells in the motor cortex. The relation between functional activity of motor cortex and symptom severity during a hand-grip motor control in vivo has not yet been investigated. This study explored both functional changes in the sensorimotor cortex and cerebellar regions and structural alterations in the cerebellum for SCA6 patients as compared to age-matched healthy controls using a multimodal imaging approach (task-based fMRI, task-based functional connectivity, and free-water diffusion MRI). Further, we tested their relation with the severity of ataxia symptoms. SCA6 patients had reduced functional activity in the sensorimotor cortex, supplementary motor area (SMA), cerebellar vermis, and cerebellar lobules I-VI (corrected P < 0.05). Reduced task-based functional connectivity between cortical motor regions (i.e., primary motor cortex and SMA) and cerebellar regions (i.e., vermis and lobules I-VI) was found in SCA6 (corrected P < 0.05). SCA6 had elevated free-water values throughout the cerebellum as compared with controls (corrected P < 0.05). Importantly, reduced functional activity in the sensorimotor cortex and SMA and increased free-water in the superior cerebellar peduncle and cerebellar lobule V were related to more severe symptoms in SCA6 (all pairs: R ≥ 0.4 and corrected P < 0.05). Current results demonstrate that impaired functional activity in sensorimotor cortex and SMA and elevated free-water of lobule V and superior cerebellar peduncle are both related to symptom severity, and may provide candidate biomarkers for SCA6.
Topics: Aged; Brain Mapping; Cerebellum; Female; Hand Strength; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Motor Activity; Neural Pathways; Sensorimotor Cortex; Severity of Illness Index; Spinocerebellar Ataxias
PubMed: 27352359
DOI: 10.1007/s00429-016-1263-4 -
Quantitative Imaging in Medicine and... Jan 2022Pulmonary part-solid nodules (PSNs) reportedly have a high possibility of malignancy, while benign PSNs are common. This study aimed to reveal the differences between...
BACKGROUND
Pulmonary part-solid nodules (PSNs) reportedly have a high possibility of malignancy, while benign PSNs are common. This study aimed to reveal the differences between benign and malignant PSNs by comparing their thin-section computed tomography (CT) features.
METHODS
Patients with PSNs confirmed by postoperative pathological examination or follow-up (at the same period) were retrospectively enrolled from March 2016 to January 2020. The clinical data of patients and CT features of benign and malignant PSNs were reviewed and compared. Binary logistic regression analysis was performed to reveal the predictors of malignant PSNs.
RESULTS
A total of 119 PSNs in 117 patients [age (mean ± standard deviation), 56±11 years; 70 women] were evaluated. Of the 119 PSNs, 44 (37.0%) were benign, and 75 (63.0%) were malignant (12 adenocarcinomas , 22 minimally invasive adenocarcinomas, and 41 invasive adenocarcinomas). There were significant differences in the patients' age and smoking history between benign and malignant PSNs. In terms of CT characteristics, malignant and benign lesions significantly differed in the following CT features: whole nodule, internal solid component, and peripheral ground-glass opacity. The binary logistic regression analysis revealed that well-defined border [odds ratio (OR), 4.574; 95% confidence interval (CI), 1.186-17.643; P=0.027] and lobulation (OR, 61.739; 95% CI, 5.230-728.860; P=0.001) of the nodule, as well as irregular shape (OR, 9.502; 95% CI, 1.788-50.482; P=0.008) and scattered distribution (OR, 13.238; 95% CI, 1.359-128.924; P=0.026) of the internal solid components were significant independent predictors distinguishing malignant PSNs. However, the lesion shape, density, and margin were similar between malignant and benign lesions.
CONCLUSIONS
Well-defined and lobulated PSNs with irregular and scattered solid components are highly likely to be malignant.
PubMed: 34993112
DOI: 10.21037/qims-21-145