Hyperdense middle cerebral artery sign predicts favorable outcome after decompressive craniectomy in patients with malignant middle cerebral artery infarction.

BACKGROUND: Malignant middle cerebral artery infarction (MMI) is a life-threatening cerebral vascular event. Early decompressive craniectomy (DC) has proven to be an effective treatment strategy. However, the ideal candidate for DC continues to be debated. PURPOSE: To investigate whether a hyperdense middle cerebral artery sign (HMCAS) provides prognostic value after DC in patients with MMI. MATERIAL AND METHODS: We reviewed clinical information and radiological parameters on computed tomography of 42 patients with MMI who underwent DC. Functional outcome was assessed according to the modified Rankin scale (mRS) at three months as follows: favorable outcome (mRS ≤ 4) versus unfavorable outcome (mRS > 4). Logistic regression analysis was used to identify predictors of functional outcome after DC in patients with MMI. RESULTS: Age (odds ratio [OR] = 0.87; 95% confidence interval [CI] = 0.78-0.97; P = 0.014) and HMCAS (OR = 7.40; 95% CI = 1.35-40.48; P = 0.021) were associated with functional outcome. The area under the receiver operating characteristic curve for predicting favorable outcome using the combination of age and HMCAS was 0.882, and the sensitivity and specificity were 0.947 and 0.696, respectively. CONCLUSION: Patients with MMI with HMCAS, as well as younger patients, often showed a favorable outcome after DC in this study.

Acute visual impairment as a main presenting symptom of non-convulsive status epilepticus: a case report.

BACKGROUND: Nonconvulsive status epilepticus (NCSE) is a state of ongoing seizure activity without convulsions. The heterogeneous and subtle clinical features of NCSE make diagnosis and treatment challenging. Here, we report a patient with NCSE who showed a main presenting symptom of acute visual impairment, which is a rare and atypical clinical symptom of NCSE. CASE PRESENTATION: A 62-year-old man was admitted to the neurology department after complaining of an inability to see in the right eye for 2 days and progressive headache. He had a history of poststroke epilepsy and vascular dementia. Physical examination revealed right visual field hemianopia, visual neglect and cognitive impairment. T2 and diffusion-weighted magnetic resonance imaging showed high signal intensity in the left temporal, parietal and occipital lobes. Electroencephalography monitoring was performed, which found continuous sharp wave discharges, especially in the regions of the left temporal, parietal and occipital lobes. These findings were most consistent with the diagnosis of NCSE. Thus, a treatment of intravenous pumping of diazepam and an oral antiepileptic drug was added immediately. After that, the visual loss in the patient recovered quickly, and electroencephalography did not find epileptiform waves. On day 11, a follow-up MRI was performed, which showed that the abnormal signals of the left temporal, parietal and occipital lobes were markedly attenuated, and the patient returned to his premorbid state with a modified Rankin Scale score of 3. CONCLUSIONS: Acute visual impairment can be seen in NCSE, and it can be reversed by administering effective antiepileptic treatment. Meanwhile, transient peri-ictal MRI abnormalities can be observed in NCSE.

Strategies to improve the efficiency of mesenchymal stem cell transplantation for reversal of liver fibrosis.

End-stage liver fibrosis frequently progresses to portal vein thrombosis, formation of oesophageal varices, hepatic encephalopathy, ascites, hepatocellular carcinoma and liver failure. Mesenchymal stem cells (MSCs), when transplanted in vivo, migrate into fibrogenic livers and then differentiate into hepatocyte-like cells or fuse with hepatocytes to protect liver function. Moreover, they can produce various growth factors and cytokines with anti-inflammatory effects to reverse the fibrotic state of the liver. In addition, only a small number of MSCs migrate to the injured tissue after cell transplantation; consequently, multiple studies have investigated effective strategies to improve the survival rate and activity of MSCs for the treatment of liver fibrosis. In this review, we intend to arrange and analyse the current evidence related to MSC transplantation in liver fibrosis, to summarize the detailed mechanisms of MSC transplantation for the reversal of liver fibrosis and to discuss new strategies for this treatment. Finally, and most importantly, we will identify the current problems with MSC-based therapies to repair liver fibrosis that must be addressed in order to develop safer and more effective routes for MSC transplantation. In this way, it will soon be possible to significantly improve the therapeutic effects of MSC transplantation for liver regeneration, as well as enhance the quality of life and prolong the survival time of patients with liver fibrosis.

Association between procalcitonin levels and carotid atherosclerosis in acute ischemic stroke patients.

BACKGROUND AND PURPOSES: Procalcitonin has been suggested as a new risk factor in atherosclerotic disease. However, whether procalcitonin levels are associated with the risk of carotid atherosclerosis remains unclear. This study aimed to investigate the relationship between procalcitonin levels and carotid atherosclerosis among patients with first-ever acute ischemic stroke. METHODS: Two hundred and thirty consecutive patients were prospectively enrolled in this study. Serum procalcitonin concentrations were measured at admission for all patients. We also performed ultrasound examination to detect the mean carotid intima-media thickness, presence of carotid-wall thickening, plaque and significant stenosis. Multiple regression analysis was used to estimate the association between procalcitonin levels and carotid atherosclerosis. RESULTS: The median procalcitonin concentration was 0.051 µg/L (interquartile range, 0.036-0.080 µg/L). Of the 230 patients, 102 (44.3%) had carotid-wall thickening, 113 (49.1%) had plaque and 77 (33.5%) had significant stenosis. After adjusting for all potential confounders by multiple logistic regression analysis, patients with procalcitonin levels in the fourth quartile, compared with the first quartile, were more likely to have carotid-wall thickening [odds ratio 2.288, 95% confidence intervals 1.042-5.021, P = 0.039] and significant stenosis [odds ratio 3.871, 95% confidence intervals 1.690-8.867, P = 0.003]. Furthermore, the linear regression analysis revealed a significant positive correlation between procalcitonin levels and the mean carotid intima-media thickness (ß = 0.162, P = 0.012). CONCLUSIONS: Higher procalcitonin concentrations at admission might be associated with carotid-wall thickening and significant stenosis in ischemic stroke patients.

Vitamin D status in chronic dialysis patients with depression: a prospective study.

BACKGROUND: Depression is the most widely acknowledged psychological problem among end-stage renal disease (ESRD) patients. Depression may be associated with VD deficiency. The aims of this study are to (a) elucidate the prospective association between HsCRP, VD contents and depressive symptoms in the dialyzed population, and (b) find the effect of calcitriol supplementation on depression in dialyzed patients. METHODS: In this prospective study, 484 dialysis patients (382 hemodialysis [HD] cases and 102 peritoneal dialysis [PD] cases; aged 18-60 years) from two hospitals in southeast China were included. The depression in these patients was evaluated using the Chinese version of Beck's Depression Inventory (BDI). All subjects answered the BDI-I questionnaire for assessment of depression levels in summer. A cut-off value of 16 was set to include dialysis patients with depression. All patients were divided into two groups depending on the absence (Group 1) or presence (Group 2) of depression. The two groups took 0.5 µg/day 1,25-Dihydroxyvitamin D orally for one year. BDI Scores were recalculated for all patients. Sociodemographic, clinical data, and serum VD contents were also collected. RESULTS: A total of 484 participants (247 men [51.0%] and 237 women [49.0%]) were surveyed. Depressive symptoms were found in 213 (44.0%) patients. The baseline serum VD level (VD2 + VD3) was 17.6 ± 7.7 nmol/L. Patients with depressive symptoms have significantly higher serum HsCRP level and significantly lower serum VD level compared with the control group. After one-year follow-up, the supplementation of 0.5 µg/day calcitriol slightly improved the microinflammatory state such as lowering mean serum HsCRP level and improving serum VD level, but not in significantly enhancing the depressive symptoms. CONCLUSIONS: Calcitriol supplementation did not significantly enhance the depressive symptoms in our dialyzed population although patients with low levels of serum VD were more depressed. Therefore, more prospective randomized controlled trials are necessary to reveal the exact cause-and-effect relationship between VD status and depressive symptoms or VD status related to some specific subtypes in dialyzed patients.

A direct estrogenic involvement in the expression of human hypocretin.

Hypocretin is synthesized exclusively in the hypothalamus and distributes inputs to several areas of the brain, which may play an important role in depression. Our previous study showed that hypocretin-1 was increased in the lateral hypothalamus in female patients with depression compared to female controls. Estrogen acts through estrogen receptor (ER)α and ERß. We studied the possibility of a direct action of estrogen receptors on the expression of human hypocretin. We found that hypocretin-1 plasma levels were significantly higher in female patients with depression than in female controls. Female depression estrogen receptors and hypocretin are colocalized in the human lateral hypothalamus, PC12, and SK-N-SH cells. The estrogen receptor response elements (ERE) that exist in the hypocretin promoter region may directly regulate the gene expression of hypocretin. The synchronicity of change of hypocretin and estradiol both in hypothalamus and plasma was verified in female rats. In the presence of estradiol, specific binding occurs between the recombinant human ER and hypocretin-ERE. Expression of ER combined with estradiol repressed hypocretin promoter activity via the ERE. In conclusion, we found that estradiol may directly affect hypocretin neurons in the human hypothalamus via ER binding to the hypocretin-ERE, which may lead to the sex-specific pathogenesis of depression.

Low (0-5) Alberta Stroke Program Early Computed Tomography Score on admission predictive of worse functional outcome after mechanical thrombectomy for anterior circulation large vessel occlusion.

BACKGROUND AND PURPOSE: We examined functional outcomes of mechanical thrombectomy (MT) procedures following anterior circulation large vessel occlusion (ACLVO)-related acute ischemic strokes (AIS). Results were based on admission non-contrast computed tomography (NCCT) studies, using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) as standard metric. METHODS: Qualifying subjects were consecutive patients (N = 343) at a single center undergoing MT for ACLVO-related AIS. Each was grouped according to ASPECTS status on admission, determined from NCCT images by two physicians. Primary clinical endpoint was functional independence, assessed via modified Rankin Scale (mRS) at 90 days. Secondary endpoints were vessel recanalization (i.e., modified Thrombolysis in Cerebral Infarction [mTICI] score), symptomatic intracranial hemorrhage (sICH), and mortality. RESULTS: In this study population (mean age, 63.6 ± 12.6 years; women, 30.3%; median baseline National Institute of Health Stroke Scale [NIHSS] score, 15.2 ± 4.5), patients were stratified by ASPECTS tier at presentation, either 0-5 (n = 50) or 6-10 (n = 293). Multivariate logistic regression showed a relation between ASPECTS values ≤ 5 and lesser chance of 90-day functional improvement (OR = 2.309, 95% confidence interval [CI] 1.012-5.271; p = 0.047), once adjusted for age, baseline NIHSS score, diabetes mellitus, HbA1c concentration, D-dimer level, occlusive location, numbers of device passes, and successful recanalization. CONCLUSIONS: ASPECTS values ≤ 5 correspond with worse long-term functional improvement (mRS scores > 2) in patients undergoing MT for ACLVO-related AIS. Other independent determinants of functional outcomes after MT are age, baseline NIHSS score, HbA1c concentration, and successful recanalization.

MSA-YOLOv5: Multi-scale attention-based YOLOv5 for automatic detection of acute ischemic stroke from multi-modality MRI images.

BACKGROUND AND OBJECTIVE: Acute ischemic stroke (AIS) is a common neurological disorder characterized by the sudden onset of cerebral ischemia, leading to functional impairments. Swift and precise detection of AIS lesions is crucial for stroke diagnosis and treatment but poses a significant challenge. This study aims to leverage multimodal fusion technology to combine complementary information from various modalities, thereby enhancing the detection performance of AIS target detection models. METHODS: In this retrospective study of AIS, we collected data from 316 AIS patients and created a multi-modality magnetic resonance imaging (MRI) dataset. We propose a Multi-Scale Attention-based YOLOv5 (MSA-YOLOv5), targeting challenges such as small lesion size and blurred borders at low resolutions. Specifically, we augment YOLOv5 with a prediction head to detect objects at various scales. Next, we replace the original prediction head with a Multi-Scale Swin Transformer Prediction Head (MS-STPH), which reduces computational complexity to linear levels and enhances the ability to detect small lesions. We incorporate a Second-Order channel attention (SOCA) module to adaptively rescale channel features by employing second-order feature statistics for more discriminative representations. Finally, we further validate the effectiveness of our method using the ISLES 2022 dataset. RESULTS: On our in-house AIS dataset, MSA-YOLOv5 achieves a 79.0% mAP0.5, substantially surpassing other single-stage models. Compared to two-stage models, it maintains a comparable performance level while significantly reducing the number of parameters and resolution. On the ISLES 2022 dataset, MSA-YOLOv5 attains an 80.0% mAP0.5, outperforming other network models by a considerable margin. MS-STPH and SOCA modules can significantly increase mAP0.5 by 2.7% and 1.9%, respectively. Visualization interpretability results show that the proposed MSA-YOLOv5 restricts high attention in the small regions of AIS lesions. CONCLUSIONS: The proposed MSA-YOLOv5 is capable of automatically and effectively detecting acute ischemic stroke lesions in multimodal images, particularly for small lesions and artifacts. Our enhanced model reduces the number of parameters while improving detection accuracy. This model can potentially assist radiologists in providing more accurate diagnosis, and enable clinicians to develop better treatment plans.

Disrupted Causal Connectivity Anchored on the Right Anterior Insula in Drug-Naive First-Episode Patients With Depressive Disorder.

Object: Major depressive disorder (MDD) has been demonstrated to be associated with abnormalities in neural networks. However, few studies examined information flow in the salience network (SN). This study examined abnormalities in the causal connectivity between the SN and whole brain in drug-naive first-episode patients with MDD in the resting state. Methods: Based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria, 23 drug-naive first-episode MDD patients and 20 matched healthy individuals were recruited and underwent a resting-state magnetic resonance scan. The acquired functional image data were preprocessed using resting-state functional magnetic resonance imaging (rs-fMRI) data analysis toolkit plus (RESTplus). Then, using the data processing & analysis for brain imaging (DPABI) software and a coefficient-based general component analysis method with the right anterior insula (rAI) as the region of interest (ROI), the causal connectivity of the SN with the whole brain and its correlation with cognitive and mental performance were examined in the resting state. Results: (1) The MDD group showed a significantly higher Hamilton Depression Rating Scale total score and significantly higher scores for anxiety, cognitive disturbance, and block factors compared with normal controls. (2) Compared with control: from whole brain to the rAI, the MDD group showed a lower causal connectivity in the left inferior frontal gyrus; from the rAI to the whole brain, the MDD group showed a lower causal connectivity in the right cingulate gyrus, the right precuneus, and extending to paracentral lobule but higher causal connectivity in the left inferior and middle frontal gyrus. (3) In the MDD group, from rAI to the whole brain, the causal connectivity values for the right cingulate gyrus/precuneus were negatively correlated with the score of Stroop Color-Word Test A, B, and C as well as interference times. Conclusion: Our results indicated disrupted causal connectivity among the default mode network (DMN), the central executive network (CEN), and SN in drug-naive first-episode MDD patients. Especially, our results suggest a unique role for rAI in the ordered or hierarchical information processing, presumed to include bottom-up and top-down reciprocal influences among the three networks in MDD.

Susceptibility-weighted imaging of cerebral fat embolism: A case report.

RATIONALE: Cerebral fat embolism (CFE) is a rare but critical disease in a clinical setting. Considering that manifestations and CT findings of CFE tend to be atypical, this condition is very difficult to diagnose. The purpose of this article was to assess the value of susceptibility-weighted imaging (SWI) in the diagnosis of CFE. PATIENT CONCERNS: Our patient was an 80-year-old woman who developed hypoxemia, quadriplegia, and progressive confusion after fracture of the right femoral neck and right superior ramus of pubis within 24 hours. DIAGNOSIS: T2-weighted magnetic resonance imaging (T2 W MRI), fluid-attenuated inversion recovery sequences, and diffusion-weighted imaging showed numerous hyperintense foci in the subcortex and white matter of both cerebral hemispheres, some of which were confluent and SWI showed multiple symmetrical punctate microhemorrhages in both hemispheres. Base on the history and MRI findings, the patient was diagnosed with CFE. INTERVENTIONS: The patient received anticoagulation and lipid-lowering therapy. OUTCOMES: The patient regained consciousness, and her muscle strength in the limbs gradually recovered. One year after discharge, the patient could independently walk on her own. LESSION: This case report shows the characteristics of CFE on SWI, which can help clinicians in diagnosing which can help clinicians in diagnosing CFE.

Automatic detection of stroke lesion from diffusion-weighted imaging via the improved YOLOv5.

BACKGROUND AND OBJECTIVE: Stroke is the second most deadly disease globally and seriously endangers people's lives and health. The automatic detection of stroke lesions from diffusion-weighted imaging (DWI) can improve the diagnosis. Recently, automatic detection methods based on YOLOv5 have been utilized in medical images. However, most of them barely capture the stroke lesions because of their small size and fuzzy boundaries. METHODS: To address this problem, a novel method for tracing the edge of the stroke lesion based on YOLOv5 (TE-YOLOv5) is proposed. Specifically, we constantly update the high-level features of the lesion using an aggregate pool (AP) module. Conversely, we feed the extracted feature into the reverse attention (RA) module to trace the edge relationship promptly. Overall, 1681 DWI images of 319 stroke patients have been collected, and experienced radiologists have marked the lesions. DWI images were randomly split into the training and test set at a ratio of 8:2. TE-YOLOv5 has been compared with the related models, and a detailed ablation analysis has been conducted to clarify the role of the RA and AP modules. RESULTS: TE-YOLOv5 outperforms its counterparts and achieves competitive performance with a precision of 81.5%, a recall of 75.8%, and a mAP@0.5 of 80.7% (mean average precision while the intersection over union is 0.5) under the same backbone. At the patient level, the positive finding rate can reach 98.51%, while the confidence is set at 80.0%. After ablating RA, the mAP@0.5 decreases to 79.6%; after ablating RA and AP, the mAP@0.5 decreases to 78.1%. CONCLUSIONS: The proposed TE-YOLOv5 can automatically and effectively detect stroke lesions from DWI images, especially for those with an extremely small size and blurred boundaries. AP and RA modules can aggregate multi-layer high-level features and concurrently track the edge relationship of stroke lesions. These detection methods might help radiologists improve stroke diagnosis and have great application potential in clinical practice.

Risk Factors of Impaired Perfusion in Patients With Symptomatic Internal Carotid Artery Steno-Occlusive Disease.

Objective: To quantitatively evaluate the impaired perfusion status of patients with symptomatic internal carotid artery (ICA) steno-occlusive disease and to explore the risk factors of impaired perfusion with computed tomography perfusion (CTP). Methods: The clinical and imaging data of 187 patients with ICA steno-occlusive disease were retrospectively analyzed. The ICA stenosis rate was divided into Grades I-IV (70-79%; 80-89%; 90-99%; 100%), and the circle of Willis was classified as four types (types I-IV). According to the literature, the value of cerebral blood flow/cerebral blood volume (CBF/CBV) of 7.55/min was used as cut-off to predict symptomatic patients. All patients were categorized into two groups: those with impaired perfusion [n = 99 (52.9%)] and those without impaired perfusion [n = 88 (47.1%)]. Symmetrical bilateral internal watershed areas were selected as the regions of interest (ROIs). Statistical analysis was made on the status of impaired perfusion and the risk factors of impaired perfusion. Results: Univariate analysis revealed that systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), types of the circle of Willis, and clinical features at admission differed between the two groups (patients with or without impaired perfusion) (p < 0.05). Multiple logistic stepwise regression analysis showed that MAP [odds ratio (OR) = 0.946, 95% confidential interval (CI) = 0.917-0.974, p < 0.001] and type IV (type I vs. IV: OR = 4.987, 95% CI = 1.955-12.723, p = 0.001) at admission were independently associated with impaired perfusion in the internal watershed areas. Conclusion: MAP and the type of circle of Willis at admission are independent risk factors associated with the impaired perfusion in patients with ICA steno-occlusive disease.

Inhalation Aromatherapy via Brain-Targeted Nasal Delivery: Natural Volatiles or Essential Oils on Mood Disorders.

Mood disorders, also often referred to as affective disorders, are a group of psychiatric illnesses that severely impact mood and its related functions. The high medical expenditures have placed a significant financial burden on patients and their families. Aromatherapy is an alternative and complementary treatment that utilizes essential oils (EOs) or volatile oils (VOs) to achieve major therapeutic goals. In general, EOs are volatile chemicals that enter the body primarily through skin absorption and/or nasal inhalation. In addition, they can work through oral administration. Inhalation aromatherapy has shown unique advantages for treating mood disorders, especially depression, anxiety and mental disorders such as sleep disorder, which have been validated over the last decade through clinical and animal studies. Accumulating evidence has shown that EOs or VOs can bypass the blood-brain barrier to target brain tissue through the nasal-brain pathway. Subsequently, they act on the cerebral cortex, thalamus, and limbic system in the brain to improve symptoms of anxiety, depression and improve sleep quality. Here, we review the natural aromatic plants' volatiles or essential oils used commonly as adjuncts to manage mood disorders and illustrate the mechanisms of inhalation aromatherapy, and mainly summarized the application of transnasal inhalation aromatherapy in depression, anxiety, and sleep disorders. We conclude that aromatherapy does not cause side-effects, which is vastly different from commonly used psychotropic drugs. Inhalation aromatherapy via brain-targeted nasal delivery offers potentially efficacious treatment for mental disorders and merits further study.

Thrombo-Inflammation and Immunological Response in Ischemic Stroke: Focusing on Platelet-Tregs Interaction.

Strokes are mainly caused by thromboembolic obstruction of a major cerebral artery. Major clinical manifestations include paralysis hemiplegia, aphasia, memory, and learning disorders. In the case of ischemic stroke (IS), hyperactive platelets contribute to advancing an acute thrombotic event progression. Therefore, the principal goal of treatment is to recanalize the occluded vessel and restore cerebral blood flow by thrombolysis or mechanical thrombectomy. However, antiplatelets or thrombolytic therapy may increase the risk of bleeding. Beyond the involvement in thrombosis, platelets also contribute to the inflammatory process induced by cerebral ischemia. Platelet-mediated thrombosis and inflammation in IS lie primarily in the interaction of platelet receptors with endothelial cells and immune cells, including T-cells, monocytes/macrophages, and neutrophils. Following revascularization, intervention with conventional antiplatelet medicines such as aspirin or clopidogrel does not substantially diminish infarct development, most likely due to the limited effects on the thrombo-inflammation process. Emerging evidence has shown that T cells, especially regulatory T cells (Tregs), maintain immune homeostasis and suppress immune responses, playing a critical immunomodulatory role in ischemia-reperfusion injury. Hence, considering the deleterious effects of inflammatory and immune responses, there is an urgent need for more targeted agents to limit the thrombotic-inflammatory activity of platelets and minimize the risk of a cerebral hemorrhage. This review highlights the involvement of platelets in neuroinflammation and the evolving role of Tregs and platelets in IS. In response to all issues, preclinical and clinical strategies should generate more viable therapeutics for preventing and managing IS with immunotherapy targeting platelets and Tregs.

IL-6, IL-8 and IL-10 polymorphisms may impact predisposition of Alzheimer's disease: a meta-analysis.

Gene polymorphisms in interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) may affect the predisposition of Alzheimer's disease (AD), but the results of the so far published studies remain controversial. The authors conducted this meta-analysis to assess relationships between IL-6/IL-8/IL-10 polymorphisms and predisposition of AD by pooling the findings of so far published studies. A comprehensive search of Pubmed, Embase, Web of Science, and CNKI was endorsed by the authors to identify the already published studies. Forty-five studies were found to be eligible for meta-analyses. The pooled meta-analyses results showed that genotypic frequencies of IL-6 - 174 G/C, IL-6 - 572 G/C and IL-10 - 1082 A/G polymorphisms among patients with AD and controls differed significantly. Moreover, genotypic frequencies of IL-6 - 174 G/C, IL-6 - 572 G/C, and IL-8 - 251 A/T polymorphisms among patients with AD and controls in Asians also differed significantly. But no such genotypic frequencies' differences were observed for IL-10 - 819 C/T and 592 C/A polymorphisms. This meta-analysis suggests that IL-6 - 174 G/C, IL-6 - 572 G/C, and IL-10 - 1082 A/G polymorphisms may affect the predisposition of AD in overall population. Moreover, IL-6 - 174 G/C, IL-6 - 572 G/C, and IL-8 - 251 A/T polymorphisms may affect the predisposition of AD in Asians.

White Matter Characteristics of Cognitive Impairment in Tap-Test Positive Idiopathic Normal Pressure Hydrocephalus: A Diffusion Tensor Tract-Based Spatial Study.

The present study was designed to systemically evaluate changes in the diffusion tensor imaging (DTI)-derived parameters of iNPH (idiopathic normal pressure hydrocephalus) patients with different responses to the tap test (TT), and to correlate cognitive impairment with white matter (WM) degeneration. This study included 22 iNPH patients and 14 healthy controls with structural magnetic resonance imaging (MRI) and DTI scanning. DTI was used to explore the differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) for all participants. DTI parameters were evaluated using an ROI (region of interest)-based and tract-based spatial statistics (TBSS) approach. Neuropsychological assessments and the idiopathic normal pressure hydrocephalus grading scoring scale (iNPHGS) were performed. Compared to the TT non-responders, the TT responders group had significantly lower FA values in the corpus callosum, cingulum cingulate gyrus, superior longitudinal fasciculus, and lower AD values in the right cingulum cingulate gyrus and the left posterior thalamic radiation. Besides, the MD values were significantly increased in the corpus callosum, left anterior corona radiata, and the RD values in the corpus callosum and cingulum cingulate gyrus. In addition, the cognitive improvement was negatively correlated with FA of the corpus callosum, cingulum cingulate gyrus, and MD values of the genu of corpus callosum. While, the cognitive improvement was positively related to the AD of the cingulum cingulate gyrus, superior longitudinal, and RD values of the corpus callosum, cingulum cingulate gyrus and uncinate fasciculus. The ROI specific WM lesions in iNPH patients are the underlying basis for cognitive impairment.

Abnormal causal connectivity of left superior temporal gyrus in drug-naïve first- episode adolescent-onset schizophrenia: A resting-state fMRI study.

This study aimed to investigate the alterations of causal connectivity between the brain regions in Adolescent-onset schizophrenia (AOS) patients. Thirty-two first-episode drug-naïve AOS patients and 27 healthy controls (HC) were recruited for resting-state functional MRI scanning. The brain region with the between-group difference in regional homogeneity (ReHo) values was chosen as a seed to perform the Granger causality analysis (GCA) and further detect the alterations of causal connectivity in AOS. AOS patients exhibited increased ReHo values in left superior temporal gyrus (STG) compared with HCs. Significantly decreased values of outgoing Granger causality from left STG to right superior frontal gyrus and right angular gyrus were observed in GC mapping for AOS. Significantly stronger causal outflow from left STG to right insula and stronger causal inflow from right middle occipital gyrus (MOG) to left STG were also observed in AOS patients. Based on assessments of the two strengthened causal connectivity of the left STG with insula and MOG, a discriminant model could identify all patients from controls with 94.9% accuracy. This study indicated that alterations of directional connections in left STG may play an important role in the pathogenesis of AOS and serve as potential biomarkers for the disease.

Changes of Hypocretin (Orexin) System in Schizophrenia: From Plasma to Brain.

Hypocretin (also called orexin) regulates various functions, such as sleep-wake rhythms, attention, cognition, and energy balance, which show significant changes in schizophrenia (SCZ). We aimed to identify alterations in the hypocretin system in SCZ patients. We measured plasma hypocretin-1 levels in SCZ patients and healthy controls and found significantly decreased plasma hypocretin-1 levels in SCZ patients, which was mainly due to a significant decrease in female SCZ patients compared with female controls. In addition, we measured postmortem hypothalamic hypocretin-1-immunoreactivity (ir), ventricular cerebrospinal fluid (CSF) hypocretin-1 levels, and hypocretin receptor (Hcrt-R) mRNA expression in the superior frontal gyrus (SFG) in SCZ patients and controls We observed a significant decrease in the amount of hypothalamic hypocretin-1 ir in SCZ patients, which was due to decreased amounts in female but not male patients. Moreover, Hcrt-R2 mRNA in the SFG was decreased in female SCZ patients compared with female controls, while male SCZ patients showed a trend of increased Hcrt-R1 mRNA and Hcrt-R2 mRNA expression compared with male controls. We conclude that central hypocretin neurotransmission is decreased in SCZ patients, especially female patients, and this is reflected in the plasma.

Discovery of new genetic loci for male sexual orientation in Han population.

Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, Pmeta = 8.36 × 10-8, OR = 1.29; rs7259428, 19q12, ZNF536, Pmeta = 7.58 × 10-8, OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese (n = 4791) and European ancestries (n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1, Pmeta = 1.95 × 10-8; rs2414487, 15q21.3, LOC145783, Pmeta = 4.53 × 10-9; rs2106525, 7q31.1, MDFIC, Pmeta = 6.24 × 10-9). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice.

Effects of Losartan on expression of connexins at the early stage of atherosclerosis in rabbits.

AIM: to investigate effects of Losartan on expression of connexin 40 and 43 (Cx40 and Cx43), in arteries at the early stage of atherosclerosis in a rabbit model. METHODS: A total of 28 male New Zealand white rabbits were divided into following groups: control group, high fat diet group, and Losartan group (10 mg/kg/day). Losartan was administrated in food for two weeks. Iliac arteries were obtained for immunohistochemistry, transmission electron microscopy, Western blot, and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Transmission electron microscopy revealed abundant gap junctions between neointimal smooth muscle cells (SMCs), which were markedly reduced by treatment. RT-PCR and Western blot assay showed that the mRNA and protein expression of Cx40 and Cx43 were elevated in the neointimal area at the early stage of atherosclerosis. The mRNA and protein expression of Cx43 were significantly down-regulated by losartan treatment but those of Cx40 were not markedly changed. CONCLUSION: Cx40 and Cx43 in the neointimal SMCs were up-regulated at the early stage of atherosclerosis. Losartan (an angiotensin-converting enzyme inhibitor) could reduce neointima proliferation and down-regulate the elevated protein expression of Cx43, suggesting the rennin-angiotensin system (RAS) plays an important role in the remodeling of gap junction between ventricular myocytes under pathological conditions.