Circumventing Drug Resistance Pathways with a Nanoparticle-Based Photodynamic Method.

Drug resistance remains the dominant impediment for cancer therapy, not only because compensatory drug resistance pathways are always activated, but also because of the cross-resistance of cancer cells to unrelated therapeutics. Herein, chemodrug-sensitive cancer cells, intrinsic drug-resistant cells, and acquired resistant cells were employed to uncover their biological response to a nanoparticle-based photodynamic method in tumoral, cellular, and molecular levels. We observed that nanoparticle-based photodynamic process with high therapeutic efficiency, intracellular delivery, and tumor penetration effect resulted in the indiscriminate and significant therapeutic outcome, in contrast to the diversiform effect of first-line chemo-drug, Temozolomide (TMZ). By real-time quantitative PCR array technique, we revealed that signals in classical resistance pathways were unaffected or downregulated, and photodynamic effect initiates cell apoptosis via downstream genes. The discovery that nanoparticulate photodynamic therapy bypasses the signals in multiple resistant pathways may imply an alternative route for combating drug resistance of cancer.

Epineurectomy of Facial Nerve Trunk for Refractory Oral-Ocular and Oculo-Oral Synkinesis Following Bell Palsy.

BACKGROUND: Synkinesis is a common sequelae after incomplete recovery from Bell palsy. Current first-line treatments include botulinum toxin injection and physical therapy. However, patients unresponsive to these treatments may require further surgery. Various surgical treatments have been reported, but no consensus has been reached for the optimal surgery. In a guinea pig model of synkinesis, the facial nerve trunk (FNT) was observed using a scanning electron microscope. Based on the results of scanning electron microscope and clinical ultrasonography, the authors chose FNT as the therapeutic target. METHODS: The authors performed epineurectomy of FNT for 11 patients with refractory oral-ocular and oculo-oral synkinesis under abnormal muscle response and facial electromyography monitoring. The postoperative assessments at 1 year were conducted using Sunnybrook Facial Grading System and Facial Disability Index scale. Furthermore, the epineurium excised during the operation was collected as the specimen and submitted for histopathological examination; the cadaveric FNT served as the control group. RESULTS: The follow-up results showed significant relief from synkinesis (4.91 ±â€Š0.37 versus 10.18 ±â€Š0.64, P < 0.01), improvement of physical (84.55 ±â€Š1.96 versus 73.18 ±â€Š3.65, P < 0.01) and social functions (77.09 ±â€Š3.24 versus 61.82 ±â€Š6.28, P < 0.01), with no worsening of facial paralysis in the patients. The histopathological examination revealed many nerve fibers in the epineurium, suggesting that FNT was the area of aberrant axon regeneration. CONCLUSIONS: Epineurectomy of FNT is a safe and effective surgical remedy. It can be considered as a surgical option for patients with refractory oral-ocular and oculo-oral synkinesis following Bell palsy.

Fatigue Detection with Spatial-Temporal Fusion Method on Covariance Manifolds of Electroencephalography.

With the increasing pressure of current life, fatigue caused by high-pressure work has deeply affected people and even threatened their lives. In particular, fatigue driving has become a leading cause of traffic accidents and deaths. This paper investigates electroencephalography (EEG)-based fatigue detection for driving by mining the latent information through the spatial-temporal changes in the relations between EEG channels. First, EEG data are partitioned into several segments to calculate the covariance matrices of each segment, and then we feed these matrices into a recurrent neural network to obtain high-level temporal information. Second, the covariance matrices of whole signals are leveraged to extract two kinds of spatial features, which will be fused with temporal characteristics to obtain comprehensive spatial-temporal information. Experiments on an open benchmark showed that our method achieved an excellent classification accuracy of 93.834% and performed better than several novel methods. These experimental results indicate that our method enables better reliability and feasibility in the detection of fatigued driving.

Overexpression of Foxc1 regenerates crushed rat facial nerves by promoting Schwann cells migration via the Wnt/ß-catenin signaling pathway.

Facial paralysis can result in severe implications for patients. A good prognosis depends on the degree of nerve regeneration. Schwann cells (SCs) play an important role in facial nerve development and regeneration through migration. Forkhead box C1 (Foxc1), a member of the forkhead transcription factor family, is implicated in cell migration. However, the role of Foxc1 in the progression after facial nerve crush remains unknown. Our aim was to evaluate the effect of Foxc1 overexpression on SC migration and recovery of facial nerves after crush injury. The rat facial nerve crush injury model was established through the use of unilateral surgery. The results showed that the expression of Foxc1 was increased in the surgery group compared to that of the control group. SCs were isolated from the sciatic nerves and cultured. Foxc1, delivered by an adeno-associated virus in vivo, or adenovirus in vitro, both induced overexpression of Foxc1, and increased the expression of CXCL12 and ß-catenin. After the transfection of Foxc1, the migration of SC was increased both in vitro and in vivo, was reduced by the inhibition of CXCL12 or ß-catenin. The facial nerve function and the nerve axon remyelination of the rats transfected with Foxc1 were significantly improved after nerve crush injury. Overall, the results demonstrated that overexpression of Foxc1 promoted SC migration by regulating CXCL12 via the Wnt/ß-catenin pathway, thus contributing to improved facial nerve function after crush injury.

Metagenomic next-generation sequencing of viruses, bacteria, and fungi in the epineurium of the facial nerve with Bell's palsy patients.

Bell's palsy (BP) represents a major cause leading to facial paralysis in the world. The etiology of BP is still unknown, and virology is the prevailing theory. The purpose of this study is to explore the pathogenic microorganisms that may be related to BP, and it is of great significance to study the pathogenesis and treatment of BP. Metagenomic next-generation sequencing (mNGS) detection was performed in the epineurium of the facial nerve of 30 BP patients who underwent facial nerve epineurium decompression. A total of 84 pathogenic microorganisms were detected in 30 clinical samples, including 4 viruses, 10 fungi, and 70 bacteria. The species with the highest detection frequency in virus was human betaherpesvirus 7 (HHV-7). The species with the highest detection frequency in Fungi was Malassezia restricta. The species with the highest detection frequency in Bacteria was Pseudomonas aeruginosa. In this study, mNGS method was firstly used to detect the pathogenic microorganisms in the epineurium of the facial nerve with BP patients. We have for the first time identified HHV-7 and aspergillus in the epineurium of the facial nerve of BP patients. These results suggest that these two pathogenic microorganisms should be considered in the pathogenesis of BP.

Exfoliation and stabilization mechanism of graphene in carbon dioxide expanded organic solvents: molecular dynamics simulations.

CO2 expanded organic solvents possess significant advantages in liquid-phase exfoliation to obtain monolayer/few-layer graphene from graphite. Further insights into the mechanism of graphene exfoliation in such solvents are essential to explore liquid-phase dispersion of graphene as a more potent alternative to chemical vapor deposition. In this study, dynamic processes of exfoliation and stabilization of graphene in CO2-N,N-dimethylformamide (DMF), CO2-N-methylpyrrolidone (NMP), CO2-dimethyl sulfoxide (DMSO), and CO2-ethanol (EtOH) were investigated using molecular dynamics simulations. The origin of the effect of each solvent on graphene exfoliation was analyzed quantitatively through potential mean force simulations. It has been found that the organic solvent in a CO2 expanded solvent should be chosen with proper surface tension, and there exist two different graphene exfoliation processes in the effective solvents, which can be described as "burger dissociation" and "extrusion-taking away" processes, respectively. In the former process, a characteristic "super-burger-like" conformation with a semi-exfoliated structure was formed, which was the deciding factor to obtain high ratio of monolayer/few-layer graphene in dispersion product. A theoretical explanation has also been provided at the molecular level to the earlier experimental phenomena. A predicted simulation of the CO2-3,3'-iminobis(N,N-dimethylpropylamine) (DMPA) system is also calculated. This investigation helps to avoid incompatible CO2 expanded organic solvents employed in the experimental studies and provides theoretical clues to understand the mechanism of exfoliation and stabilization of graphene in such solvents.

Microvascular Decompression Alone without Rhizotomy Is an Effective Way of Treating Glossopharyngeal Neuralgia: Clinical Analysis of 46 Cases.

BACKGROUND: Microvascular decompression (MVD) has been the right choice for glossopharyngeal neuralgia (GPN) patients. However, whether glossopharyngeal/vagal nerve root rhizotomy should be combined with MVD is still controversial. OBJECTIVE: To evaluate whether glossopharyngeal/vagal nerve root rhizotomy during MVD is necessary for the treatment of GPN. METHODS: We performed a retrospective study of 46 GPN patients who underwent MVD surgery alone in our hospital, and their patient demographics, clinical presentations, and intraoperative findings are shown. The immediate and long-term follow-up outcomes were investigated to show the treatment's efficiency and safety; the outcome was also compared with our previous study. The relevant literature was reviewed to show complications for GPN patients undergoing glossopharyngeal/vagal nerve root rhizotomy with MVD. RESULTS: The most common offending vessel was the posterior inferior cerebellar artery (60.9%). 100% of the patients were pain-free (score of I on the Barrow Neurological Institute pain intensity [BNI-P] scale) immediately after MVD surgery, while 1 patient relapsed with occasional pain 12 months after the operation (score of III on the BNI-P scale). Poor wound healing and hearing loss were found in 1 case each. No complications related to the glossopharyngeal nerve/vagal nerve were reported. Some surgical techniques, such as thorough exploration of the CN IX-X rootlets, full freeing from arachnoid adhesions, and usage of a moist gelatin sponge, can improve the success rate of the operation. CONCLUSIONS: MVD alone without rhizotomy is an effective and safe method for patients with GPN.

20(S)-ginsenoside-Rg3 reverses temozolomide resistance and restrains epithelial-mesenchymal transition progression in glioblastoma.

Glioblastoma multiforme (GBM) is one of the most malignant human intracranial tumors. Temozolomide (TMZ) is the primary alkylating agent for GBM patients. However, many GBM patients are resistant to TMZ. Therefore, patients with GBM urgently need more effective therapeutic options. 20(S)-ginsenoside-Rg3 (20(S)-Rg3) is a natural chemical with anti-tumor effects, but at present there is little understanding of its functional mechanism. Several research reports have demonstrated that O6 -methylguanine DNA-methyltransferase (MGMT) repairs damaged DNA and contributes to TMZ resistance in gliomas. In addition, recent studies have shown that MGMT gene expression could be regulated by the Wnt/ß-catenin pathway. However, whether 20(S)-Rg3 inhibits MGMT expression and augments chemosensitivity to Temozolomide (TMZ) in glioma cells remains unclear. In this study, we explored the modulating effects of 20(S)-Rg3 on MGMT. We used glioma cell lines, primary cell strain (including T98G, U118 and GBM-XX; all of them are MGMT-positive glioma cell lines) and xenograft glioma models to examine whether 20(S)-Rg3 increased the sensitivity to TMZ and to reveal the underlying mechanisms. We found that the MGMT expression was effectively downregulated by 20(S)-Rg3 via the Wnt/ß-catenin pathway in glioma cell lines, and TMZ resistance was significantly reversed by 20(S)-Rg3. Meanwhile, 20(S)-Rg3 shows no obvious cytotoxicity at its effective dose and is well tolerated in vivo. In addition, we found that 20(S)-Rg3 significantly restrains the epithelial-mesenchymal transition (EMT) progression of glioma cells. Taken together, these results indicate that 20(S)-Rg3 may be a novel agent to use in treatment of GBM, especially in TMZ-resistant GBM with high MGMT expression.

Treatment of Venous Hemorrhage Between Vestibulocochlear Nerve and Hypertrophic Flocculus During Microvascular Decompression Procedure for Hemifacial Spasm.

Hemifacial spasm is a kind of painless, intermittent, involuntary, and irregular unilateral facial muscles convulsion. Microvascular decompression has become the standard surgical procedure for hemifacial spasm after years of popularization and development. In the article, the authors described in detail a therapeutic strategy for rapid intracranial venous bleeding between vestibulocochlear nerve and hypertrophic flocculus. When simple compression hemostasis failed, the authors applied fibrin glue and gelatin sponges for hemostasis and finally successfully controlled venous bleeding. The patient's symptoms were completely relieved after operation. Routine postoperative examination of head computed tomography revealed no intracranial hemorrhage. The combination of fibrin glue and gelatin sponges may be a possible solution for complicated and intractable venous hemorrhage during microvascular decompression procedure in some patients with hemifacial spasm.

Treatment of Posterior Inferior Cerebellar Artery Adhesion on Petrous Bone During Microvascular Decompression Procedure for Hemifacial Spasm: Technique Note.

Hemifacial spasm is a hyperactive cranial nerve disease mainly characterized by unilateral facial muscles paroxysmal, involuntary, irregular and clonic convulsion. Standard microvascular decompression is currently the most effective solution. During operation, it is pivotal to conduct a sharp dissection of arachnoid membrane around the caudal cranial nerves and facial, auditory nerves for fully exposure of pontomedullary sulcus, and lateral pontine region. In this article, the authors demonstrate a hemifacial spasm patient who underwent microvascular decompression successfully in their department. But the authors encountered a serious barrier to the exploration of facial nerve and its offending vessels before decompression and found that posterior inferior cerebellar artery tightly adhered to petrous bone and closely attached to a petrosal vein on cerebellar surface at the same time. The petrosal vein was also seriously stuck to petrous bone. To solve this practical difficulty, the authors employed sharp point knife blade and microsurgical scissors boldly to separate posterior inferior cerebellar artery from the dura mater of petrous bone bidirectionally and bipolar coagulation for effective hemostasis. And then the authors moderately dealt with the surface adhesion of cerebellum for smooth exploration instead of processing the petrosal vein attached to petrous bone because the authors did not want to sacrifice this vein. Relative to the routine microvascular decompression for hemifacial spasm, treatments of the adhensions before decompression were the key technology of this operation.

MicroRNA-150 negatively regulates the function of CD4(+) T cells through AKT3/Bim signaling pathway.

Donor-derived CD4(+) T lymphocytes are the major effector cells directly involved in the development of graft-versus-host disease (GVHD). As a negative regulator of immune cell differentiation and development, microRNA-150 (miR-150) induces immunological tolerance in CD4(+) T cells after transplantation. However, the specific mechanisms have not been fully elucidated. In this study, we demonstrated that miR-150 is capable of not only inhibiting proliferation and activation of CD4(+) T cells but also promoting apoptosis. Mechanistically, miR-150 targets v-akt murine thymoma viral oncogene homolog 3 (AKT3), and subsequently downregulates B-cell lymphoma 2 (Bcl-2) interacting mediator of cell death (BIM). We have also demonstrated that re-expression of AKT3 reversed miR-150-mediated inhibition of CD4(+) T lymphocyte development. Therefore, we conclude that miR-150 negatively regulates CD4(+) T cell function by inhibiting the AKT3/BIM signaling pathway. These findings also suggest that manipulating the levels of miRNA-150 could be a valuable strategy in prevention and/or treatment of acute graft-versus-host disease.

Impact of lithography on the fluorescence dynamics of self-assembled fluorophores.

Micro- and nano-patterned fluorescent materials are important for many photonic devices and applications. In this paper, we investigate the impact of three common lithographical techniques, deposition and removal of sacrificial masks, ultraviolet ablation, and focused ion beam milling, on self-assembled fluorophores. We find that different patterning techniques can dramatically change the fluorescence lifetime of the fluorophores and that the degree of modification depends on the patterning techniques.

CpSmt3, an ortholog of small ubiquitin-like modifier, is essential for growth, organelle function, virulence, and antiviral defense in Cryphonectria parasitica.

Introduction: SUMOylation is an important post-translational modification that regulates the expression, localization, and activity of substrate proteins, thereby participating in various important cellular processes such as the cell cycle, cell metabolism, gene transcription, and antiviral activity. However, the function of SUMOylation in phytopathogenic fungi has not yet been adequately explored. Methods: A comprehensive analysis composed of proteomics, affinity pull-down, molecular and cellular approaches was performed to explore the roles of SUMOylation in Cryphonectria parasitica, the fungal pathogen responsible for chestnut blight. Results and discussion: CpSmt3, the gene encoding the SUMO protein CpSmt3 in C. parasitica was identified and characterized. Deletion of the CpSmt3 gene resulted in defects in mycelial growth and hyphal morphology, suppression of sporulation, attenuation of virulence, weakening of stress tolerance, and elevated accumulation of hypovirus dsRNA. The ΔCpSmt3 deletion mutant exhibited an increase in mitochondrial ROS, swollen mitochondria, excess autophagy, and thickened cell walls. About 500 putative SUMO substrate proteins were identified by affinity pull-down, among which many were implicated in the cell cycle, ribosome, translation, and virulence. Proteomics and SUMO substrate analyses further revealed that deletion of CpSmt3 reduced the accumulation of CpRho1, an important protein that is involved in TOR signal transduction. Silencing of CpRho1 resulted in a phenotype similar to that of ΔCpSmt3, while overexpression of CpRho1 could partly rescue some of the prominent defects in ΔCpSmt3. Together, these findings demonstrate that SUMOylation by CpSmt3 is vitally important and provide new insights into the SUMOylation-related regulatory mechanisms in C. parasitica.

Modulation of temporal and occipital cortex by acupuncture in non-menstrual MWoA patients: a rest BOLD fMRI study.

OBJECTIVE: To investigate the changes in amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) values before and after acupuncture in young women with non-menstrual migraine without aura (MWoA) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI). METHODS: Patients with non-menstrual MWoA (Group 1, n = 50) and healthy controls (Group 2, n = 50) were recruited. fMRI was performed in Group 1 at 2 time points: before acupuncture (time point 1, TP1); and after the end of all acupuncture sessions (time point 2, TP2), and performed in Group 2 as a one-time scan. Patients in Group 1 were assessed with the Migraine Disability Assessment Questionnaire (MIDAS) and the Short-Form McGill Pain Questionnaire (SF-MPQ) at TP1 and TP2 after fMRI was performed. The ALFF and DC values were compared within Group 1 at two time points and between Group 1 and Group2. The correlation between ALFF and DC values with the statistical differences and the clinical scales scores were analyzed. RESULTS: Brain activities increased in the left fusiform gyrus and right angular gyrus, left middle occipital gyrus, and bilateral prefrontal cortex and decreased in left inferior parietal lobule in Group 1, which had different ALFF values compared with Group 2 at TP1. The bilateral fusiform gyrus, bilateral inferior temporal gyrus and right middle temporal gyrus increased and right angular gyrus, right superior marginal gyrus, right inferior parietal lobule, right middle occipital gyrus, right superior frontal gyrus, right middle frontal gyrus, right anterior central gyrus, and right supplementary motor area decreased in activity in Group 1 had different DC values compared with Group 2 at TP1. ALFF and DC values of right inferior temporal gyrus, right fusiform gyrus and right middle temporal gyrus were decreased in Group1 at TP1 compared with TP2. ALFF values in the left middle occipital area were positively correlated with the pain degree at TP1 in Group1 (correlation coefficient r, r = 0.827, r = 0.343; P < 0.01, P = 0.015). The DC values of the right inferior temporal area were positively correlated with the pain degree at TP1 in Group 1 (r = 0.371; P = 0.008). CONCLUSION: Spontaneous brain activity and network changes in young women with non-menstrual MwoA were altered by acupuncture. The right temporal area may be an important target for acupuncture modulated brain function in young women with non-menstrual MwoA.

Cerebral abnormalities in HIV-infected individuals with neurocognitive impairment revealed by fMRI.

Although the combination antiretroviral treatment (cART) has considerably lowered the risk of HIV associated dementia (HAD), the incidence of neurocognitive impairments (NCI) has not decreased likely due to the insidious and slow progressive nature of HIV infection. Recent studies showed that the resting-state functional magnetic resonance imaging (rs-fMRI) is a prominent technique in helping the non-invasive analysis of neucognitive impairment. Our study is to explore the neuroimaging characteristics among people living with HIV (PLWH) with or without NCI in terms of cerebral regional and neural network by rs-fMRI, based on the hypothesis that HIV patients with and without NCI have independent brain imaging characteristics. 33 PLWH with NCI and 33 PLWH without NCI, recruited from the Cohort of HIV-infected associated Chronic Diseases and Health Outcomes, Shanghai, China (CHCDO) which was established in 2018, were categorized into the HIV-NCI and HIV-control groups, respectively, based on Mini-Mental State Examination (MMSE) results. The two groups were matched in terms of sex, education and age. Resting-state fMRI data were collected from all participants to analyze the fraction amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) to assess regional and neural network alterations in the brain. Correlations between fALFF/FC values in specific brain regions and clinical characteristics were also examined. The results showed increased fALFF values in the bilateral calcarine gyrus, bilateral superior occipital gyrus, left middle occipital gyrus, and left cuneus in the HIV-NCI group compared to the HIV-control group. Additionally, increased FC values were observed between the right superior occipital gyrus and right olfactory cortex, bilateral gyrus rectus, and right orbital part of the middle frontal gyrus in the HIV-NCI group. Conversely, decreased FC values were found between the left hippocampus and bilateral medial prefrontal gyrus, as well as bilateral superior frontal gyrus. The study concluded that abnormal spontaneous activity in PLWH with NCI primarily occurred in the occipital cortex, while defects in brain networks were mostly associated with the prefrontal cortex. The observed changes in fALFF and FC in specific brain regions provide visual evidence to enhance our understanding of the central mechanisms underlying the development of cognitive impairment in HIV patients.

Exploration of the effects of Yang's pricking-cupping therapy on eczema-induced pruritus based on rs-fMRI. / 基于rs-fMRI探讨杨氏絮刺火罐对湿疹瘙痒的影响.

OBJECTIVES: To explore the clinical effect of Yang's pricking-cupping therapy and its central mechanism in treatment of eczema-induced pruritus using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Fifty patients with eczema-induced pruritus were enrolled in the observation group, and 50 healthy subjects were enrolled in the control group. No any intervention was delivered in the control group. Yang's pricking-cupping therapy was operated at Dazhui (GV 14) and bilateral Quchi (LI 11), Xuehai (SP 10) and Sanyinjiao (SP 6), once a week, lasting 6 weeks in the observation group. The scores of the 12-item pruritus severity scale (12-PSS), the eczema area and severity index (EASI), the dermatology life quality index (DLQI), the Pittsburgh sleep quality index (PSQI), and the self-rating anxiety scale (SAS) were compared before and after treatment in the observation group. The rs-fMRI scanning was conducted and the regional homogeneity (ReHo) analysis performed in all of the participants before and after treatment in the observation group, as well as at the time of subject enrollment in the control group. The correlation was analyzed between ReHo values in the different areas of the brain and the scores of the above scales. RESULTS: Compared with those before treatment, the scores of 12-PSS, EASI, DLQI, PSQI, and SAS were reduced after treatment in the observation group (P<0.01, P<0.05). ReHo values were increased in the right caudate nucleus, the right middle temporal gyrus, the right orbitofrontal gyrus, the right thalamus and the left angular gyrus before treatment in the observation group when compared with those in the control group (P<0.001); and ReHo values in the above areas of the brain were decreased after treatment when compared with those before treatment in the observation group (P<0.001). In comparison with the control group, ReHo values were reduced in the left middle temporal gyrus, the left superior parietal lobule and the left supplementary motor area in the observation group before treatment (P<0.001); while when compared with those before treatment, ReHo values in the above areas of the brain were elevated after treatment in the observation group (P<0.001). Before treatment, ReHo value in the left supplementary motor area was positively correlated with 12-PSS score (r=0.432, P=0.004), and the value in the right orbitofrontal gyrus was negatively correlated with PSQI score (r=-0.318, P=0.04) in the observation group. After treatment, ReHo value in the left superior parietal lobule was positively correlated with 12-PSS score (r=0.384, P=0.012) in the observation group. CONCLUSIONS: The abnormal cerebral functional activities are exhibited in multiple areas of the brain involved in stimulus response, emotional regulation, behavior control and attention in the patients with eczema-induced pruritus. Yang's pricking-cupping therapy can effectively relieve the pruritus symptoms and skin lesions of the patients, which may be related to reversing the abnormal cerebral functional activities induced by pruritus.

Latency of Spread: An Important Clinical Indicator Reflecting the Complexity Level of Offending Vessels in Patients with Typical Hemifacial Spasm.

AIM: The latency of spread refers to the time interval between the onset of the orbicularis oculi muscle and the involvement of lower facial muscles, which varies among patients with typical hemifacial spasm. In this study, we aimed to investigate whether the latency of spread could reflect the complexity level of intraoperative offending vessels. MATERIAL AND METHODS: A total of 96 patients with typical hemifacial spasm who underwent microvascular decompression (MVD) in our department between August 2018 and December 2019 were retrospectively analyzed. We introduced a new concept of three complexity levels of offending vessels based on six vascular classifications proposed by Kwan Park et al. and the difficulty of intraoperative management reviewed by surgical videos. One-way analysis of variance, Spearman correlation analysis, and multivariate linear regression analysis were performed. RESULTS: There were significant differences in latency of spread among the three complexity levels of offending vessels (p 0.01). Spearman correlation analysis showed a strong negative correlation between vascular complexity level and the latency of spread (r = -0.7997, p 0.0001). Multivariate linear regression analysis showed that the vascular complexity level was the main factor affecting the latency of spread (p 0.01). In contrast, other factors such as sex, side, age, hypertension, and diabetes had no significant effects. CONCLUSION: As an important clinical indicator, the latency of spread can reflect the complexity level of offending vessels in patients with typical hemifacial spasm before MVD.

A New Application of Gelatin Sponge in the Treatment of Hemifacial Spasm by Microvascular Decompression: A Technical Note.

OBJECTIVES: Microvascular decompression (MVD) for facial nerve remains the highly efficient hemifacial spasm (HFS) treatment. Nonetheless, a variety of cases have poor response to MVD. Using Teflon plus gelatin sponge in MVD seems to be a good solution. No existing study has examined the efficacy of using Teflon combined with gelatin sponge during MVD for HFS. Therefore, this study aimed to compare the efficacy of Teflon combined with gelatin sponge in HFS patients relative to that of Teflon alone. PATIENTS AND METHODS: We retrospectively compared the follow-up results of patients treated with Teflon and gelatin sponge with those treated with Teflon alone previously. Six hundred and eighty-eight primary HFS patients undergoing surgery from January 2010 to January 2018 were retrospectively analyzed. Three hundred and forty-seven cases received simple Teflon, while 342 cases underwent Teflon combined with gelatin sponge. RESULTS: In the Teflon plus gelatin sponge group, the incidences of facial palsy and hearing loss at 1 day, 1 year, and 2 years following surgery was significantly lower than those in the simple Teflon group. Differences in the success rates between Teflon plus gelatin sponge and the simple Teflon group were not statistically significant at 1 day, 1 year, and 2 years after surgery. The recurrence rate in the Teflon plus gelatin sponge group was significantly lower at 2 years. CONCLUSION: For HFS patients undergoing MVD, using Teflon plus gelatin sponge can remarkably reduce the incidence of recurrence, facial palsy, and hearing loss compared with those using Teflon alone.

Internetwork Connectivity Predicts Cognitive Decline in Parkinson's and Is Altered by Genetic Variants.

In Parkinson's disease (PD) functional changes in the brain occur years before significant cognitive symptoms manifest yet core large-scale networks that maintain cognition and predict future cognitive decline are poorly understood. The present study investigated internetwork functional connectivity of visual (VN), anterior and posterior default mode (aDMN, pDMN), left/right frontoparietal (LFPN, RFPN), and salience (SN) networks in 63 cognitively normal PD (PDCN) and 43 healthy controls who underwent resting-state functional MRI. The functional relevance of internetwork coupling topologies was tested by their correlations with baseline cognitive performance in each group and with 2-year cognitive changes in a PDCN subsample. To disentangle heterogeneity in neurocognitive functioning, we also studied whether α-synuclein (SNCA) and microtubule-associated protein tau (MAPT) variants alter internetwork connectivity and/or accelerate cognitive decline. We found that internetwork connectivity was largely preserved in PDCN, except for reduced pDMN-RFPN/LFPN couplings, which correlated with poorer baseline global cognition. Preserved internetwork couplings also correlated with domain-specific cognition but differently for the two groups. In PDCN, stronger positive internetwork coupling topologies correlated with better cognition at baseline, suggesting a compensatory mechanism arising from less effective deployment of networks that supported cognition in healthy controls. However, stronger positive internetwork coupling topologies typically predicted greater longitudinal decline in most cognitive domains, suggesting that they were surrogate markers of neuronal vulnerability. In this regard, stronger aDMN-SN, LFPN-SN, and/or LFPN-VN connectivity predicted longitudinal decline in attention, working memory, executive functioning, and visual cognition, which is a risk factor for dementia. Coupling strengths of some internetwork topologies were altered by genetic variants. PDCN carriers of the SNCA risk allele showed amplified anticorrelations between the SN and the VN/pDMN, which supported cognition in healthy controls, but strengthened pDMN-RFPN connectivity, which maintained visual memory longitudinally. PDCN carriers of the MAPT risk allele showed greater longitudinal decline in working memory and increased VN-LFPN connectivity, which in turn predicted greater decline in visuospatial processing. Collectively, the results suggest that cognition is maintained by functional reconfiguration of large-scale internetwork communications, which are partly altered by genetic risk factors and predict future domain-specific cognitive progression.

Functional topologies of spatial cognition predict cognitive and motor progression in Parkinson's.

Background: Spatial cognition deteriorates in Parkinson's disease (PD), but the neural substrates are not understood, despite the risk for future dementia. It is also unclear whether deteriorating spatial cognition relates to changes in other cognitive domains or contributes to motor dysfunction. Objective: This study aimed to identify functional connectivity abnormalities in cognitively normal PD (PDCN) in regions that support spatial cognition to determine their relationship to interfacing cognitive functions and motor disability, and to determine if they predict cognitive and motor progression 2 years later in a PDCN subsample. Methods: Sixty-three PDCN and 43 controls underwent functional MRI while judging whether pictures, rotated at various angles, depicted the left or right hand. The task activates systems that respond to increases in rotation angle, a proxy for visuospatial difficulty. Angle-modulated functional connectivity was analyzed for frontal cortex, posterior cortex, and basal ganglia regions. Results: Two aberrant connectivity patterns were found in PDCN, which were condensed into principal components that characterized the strength and topology of angle-modulated connectivity. One topology related to a marked failure to amplify frontal, posterior, and basal ganglia connectivity with other brain areas as visuospatial demands increased, unlike the control group (control features). Another topology related to functional reorganization whereby regional connectivity was strengthened with brain areas not recruited by the control group (PDCN features). Functional topologies correlated with diverse cognitive domains at baseline, underscoring their influences on spatial cognition. In PDCN, expression of topologies that were control features predicted greater cognitive progression longitudinally, suggesting inefficient communications within circuitry normally recruited to handle spatial demands. Conversely, stronger expression of topologies that were PDCN features predicted less longitudinal cognitive decline, suggesting functional reorganization was compensatory. Parieto-occipital topologies (control features) had different prognostic implications for longitudinal changes in motor disability. Expression of one topology predicted less motor decline, whereas expression of another predicted increased postural instability and gait disturbance (PIGD) feature severity. Concurrently, greater longitudinal decline in spatial cognition predicted greater motor and PIGD feature progression, suggesting deterioration in shared substrates. Conclusion: These novel discoveries elucidate functional mechanisms of visuospatial cognition in PDCN, which foreshadow future cognitive and motor disability.