Endovascular management of intracranial carotid blowout syndrome in patients with head and neck cancer.

BACKGROUND: Carotid blowout syndrome is a serious complication of head and neck cancer (HNC) that may involve the intracranial or extracranial internal carotid artery (ICA). Although parent artery occlusion (PAO) is the major endovascular treatment for intracranial carotid blowout syndrome (iCBS), the efficacy of using a balloon-expandable coronary stent-graft (BES) remains unclear. METHODS: This was a quasi-randomized trial, prospective study that included patients with iCBS treated by BES or PAO between 2018 and 2024. Patients were allocated to either group based on the last digit of their chart number; even numbers went to the BES group and odd numbers to the PAO group. The inclusion criteria of iCBS included the pathological process of CBS involving petrous and/or cavernous ICA detected by both imaging and clinical features. The primary outcome was defined as rebleeding events after intervention. The secondary outcome was defined as neurological complication after intervention. RESULTS: Fifty-nine patients with 61 iCBS lesions were enrolled. Thirty-three iCBS lesions were treated with BES and 28 underwent PAO. The results for the BES group versus the PAO group, respectively, were: rebleeding events, 5/33 (15.1%) vs 5/28 (17.8%) (p=0.78); neurological complication, 5/33 (15.1%) vs 5/28 (17.8%) (p=0.78); median hemostatic time (months), 10.0 vs 11.5 (p=0.22); and median survival time (months), 10.0 vs 11.5 (p=0.39). CONCLUSIONS: No significant difference in rebleeding risk or neurological complication was observed between the BES and PAO groups. Our study confirmed the safety and effectiveness of applying BES for iCBS in HNC patients.

Exploring cognitive load through neuropsychological features: an analysis using fNIRS-eye tracking.

Cognition is crucial to brain function, and accurately classifying cognitive load is essential for understanding the psychological processes across tasks. This paper innovatively combines functional near-infrared spectroscopy (fNIRS) with eye tracking technology to delve into the classification of cognitive load at the neurocognitive level. This integration overcomes the limitations of a single modality, addressing challenges such as feature selection, high dimensionality, and insufficient sample capacity. We employ fNIRS-eye tracking technology to collect neural activity and eye tracking data during various cognitive tasks, followed by preprocessing. Using the maximum relevance minimum redundancy algorithm, we extract the most relevant features and evaluate their impact on the classification task. We evaluate the classification performance by building models (naive Bayes, support vector machine, K-nearest neighbors, and random forest) and employing cross-validation. The results demonstrate the effectiveness of fNIRS-eye tracking, the maximum relevance minimum redundancy algorithm, and machine learning techniques in discriminating cognitive load levels. This study emphasizes the impact of the number of features on performance, highlighting the need for an optimal feature set to improve accuracy. These findings advance our understanding of neuroscientific features related to cognitive load, propelling neural psychology research to deeper levels and holding significant implications for future cognitive science.

Early Improvement in Interstitial Fluid Flow in Patients With Severe Carotid Stenosis After Angioplasty and Stenting.

Background and Purpose: This study aimed to investigate early changes in interstitial fluid (ISF) flow in patients with severe carotid stenosis after carotid angioplasty and stenting (CAS). Methods: We prospectively recruited participants with carotid stenosis ≥80% undergoing CAS at our institute between October 2019 and March 2023. Magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI), and the Mini-Mental State Examination (MMSE) were performed 3 days before CAS. MRI with DTI and MMSE were conducted within 24 hours and 2 months after CAS, respectively. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was calculated from the DTI data to determine the ISF status. Increments were defined as the ratio of the difference between post- and preprocedural values to preprocedural values. Results: In total, 102 participants (age: 67.1±8.9 years; stenosis: 89.5%±5.7%) with longitudinal data were evaluated. The DTI-ALPS index increased after CAS (0.85±0.15; 0.85 [0.22] vs. 0.86±0.14; 0.86 [0.21]; P=0.022), as did the MMSE score (25.9±3.7; 24.0 [4.0] vs. 26.9±3.4; 26.0 [3.0]; P<0.001). Positive correlations between increments in the DTI-ALPS index and MMSE score were found in all patients (rs=0.468; P<0.001). Conclusion An increased 24-hour post-CAS DTI-ALPS index suggests early improvement in ISF flow efficiency. The positive correlation between the 24-hour DTI-ALPS index and 2-month MMSE score increments suggests that early ISF flow improvement may contribute to long-term cognitive improvement after CAS.

Percutaneous transluminal angioplasty and stenting for severe stenosis of the intracranial carotid artery and its branches: Comparison of the Wingspan stent vs the Credo stent.

BACKGROUND: Despite the widespread use of the Wingspan stent system for treating severe medically refractory intracranial artery stenosis (SMR-ICAS), a new Credo stent system was approved because it could integrate stent delivery within the balloon catheter. However, the therapeutic outcomes of these two systems have not been compared. This preliminary study aimed to compare the results of percutaneous angioplasty and stenting (PTAS) in SMR-ICAS patients treated with either Wingspan or Credo stents within the anterior cerebral circulation. METHODS: SMR-ICAS patients with >70% stenosis in the anterior circulation who underwent PTAS using either the Wingspan or Credo stent system were retrospectively analyzed. We evaluated the technical success, safety, and outcomes of the two-stent systems. RESULTS: A total of 29 patients were analyzed, including 17 patients treated with Wingspan stents and 12 with Credo stents. The outcomes of the Wingspan stent vs Credo stent were as follows: technical success (16/17 [94%] vs 11/12 [92%], p = 1.00); periprocedural intracranial hemorrhage (2/17 [12%] vs 0/12 [0%], p = 0.50); silent embolic ischemic lesions on periprocedural magnetic resonance imaging (MRI) (13/17 [76%] vs 7/12 [58%], p = 0.42); and significant (>50%) in-stent restenosis in 1 year (4/17 [24%] vs 2/12 [17%], p = 1.00). No recurrent stroke or mortality was noted within 30 days after the procedures or during the 1-year follow-up period. CONCLUSION: The technical success, safety, and outcomes of the Credo stent system were comparable to those of the Wingspan stent system in the management of SMR-ICAS patients. Further large-scale studies are warranted to substantiate these findings.

Exploratory insights into prefrontal cortex activity in continuous glucose monitoring: findings from a portable wearable functional near-infrared spectroscopy system.

The escalating global prevalence of diabetes highlights an urgent need for advancements in continuous glucose monitoring (CGM) technologies that are non-invasive, accurate, and user-friendly. Here, we introduce a groundbreaking portable wearable functional near-infrared spectroscopy (fNIRS) system designed to monitor glucose levels by assessing prefrontal cortex (PFC) activity. Our study delineates the development and application of this novel fNIRS system, emphasizing its potential to revolutionize diabetes management by providing a non-invasive, real-time monitoring solution. Fifteen healthy university students participated in a controlled study, where we monitored their PFC activity and blood glucose levels under fasting and glucose-loaded conditions. Our findings reveal a significant correlation between PFC activity, as measured by our fNIRS system, and blood glucose levels, suggesting the feasibility of fNIRS technology for CGM. The portable nature of our system overcomes the mobility limitations of traditional setups, enabling continuous, real-time monitoring in everyday settings. We identified 10 critical features related to blood glucose levels from extensive fNIRS data and successfully correlated PFC function with blood glucose levels by constructing predictive models. Results show a positive association between fNIRS data and blood glucose levels, with the PFC exhibiting a clear response to blood glucose. Furthermore, the improved regressive rule principal component analysis (PCA) method outperforms traditional PCA in model prediction. We propose a model validation approach based on leave-one-out cross-validation, demonstrating the unique advantages of K-nearest neighbor (KNN) models. Comparative analysis with existing CGM methods reveals that our paper's KNN model exhibits lower RMSE and MARD at 0.11 and 8.96%, respectively, and the fNIRS data were highly significant positive correlation with actual blood glucose levels (r = 0.995, p < 0.000). This study provides valuable insights into the relationship between metabolic states and brain activity, laying the foundation for innovative CGM solutions. Our portable wearable fNIRS system represents a significant advancement in effective diabetes management, offering a promising alternative to current technologies and paving the way for future advancements in health monitoring and personalized medicine.

Endovascular Management of Post-Irradiated Carotid Blowout Syndrome in Patients with Lower Neck Cancers.

OBJECTIVE: Lower neck cancers (LNCs) include specific tumour types and have some different vascular supply or collaterals from other head and neck cancers. This prospective study evaluated the outcome of endovascular management of post-irradiated carotid blowout syndrome (PCBS) in patients with LNC by comparing reconstructive management (RE) and deconstructive management (DE). METHODS: This was a single centre, prospective cohort study. Patients with LNC complicated by PCBS between 2015 and 2021 were enrolled for RE or DE. RE was performed by stent graft placement covering the pathological lesion and preventive external carotid artery (ECA) embolisation without balloon test occlusion (BTO). DE was performed after successful BTO by permanent coil or adhesive agent embolisation of the internal carotid artery (ICA) and ECA to common carotid artery, or ICA occlusion alone if the pathological lesion was ICA only. Cross occlusion included the proximal and distal ends of the pathological lesion in all patients. Re-bleeding events, haemostatic period, and neurological complications were evaluated. RESULTS: Fifty-nine patients (mean age 58.5 years; 56 male) were enrolled, including 28 patients undergoing RE and 31 patients undergoing DE. Three patients originally grouped to DE were transferred to RE owing to failed BTO. The results of RE vs. DE were as follows: rebleeding events, 13/28 (46%) vs. 10/31 (32%) (p = .27); haemostatic period, 9.4 ± 14.0 months vs. 14.2 ± 27.8 months (p = .59); neurological complication, 4/28 (14%) vs. 5/31 (16%) (p = .84); and survival time, 11.8 ± 14.6 months vs. 15.1 ± 27.5 months (p = .61). CONCLUSION: No difference in rebleeding risk or neurological complications was observed between the DE and RE groups. RE could be used as a potential routine treatment for PCBS in patients with LNC.

Tumefactive Demyelination Lesions: Report on three cases.

PURPOSE: Tumefactive demyelination (TD) lesion and its subtype Balo's concentric sclerosis (BCS), are rare manifestations of central nervous system demyelinating disease. Because of its rarity, physicians might hesitate in reaching a diagnosis or initiating steroid pulse therapy. This study aims at pinpointing the key neuroimaging features to distinguish TD lesions from surgical conditions, and illustrating the clinical outcomes of patients with TD lesions. CASE REPORT: Two of the three patients had solitary TD lesions, one 47-year-old man presenting with newly onset seizure and another 54-year-old women suffering from progressive hemiparesis. The male patient underwent craniotomy for mass excision without further steroid therapy, while the female patient received methylprednisolone pulse therapy only. Both patients remained free of clinical and radiological relapses over the past 6-7 years, leading to the diagnosis of clinically isolated syndrome. The third case is a 30-year-old woman with subacute onset of dysarthria and hemiparesis. She had two BCS lesions along with other demyelinating lesions in the juxtacortical and periventricular regions, cerebellar peduncles, and spinal cord, fulfilling dissemination in time and space. Her neurological deficits resolved after pulse therapy, and she received long-term disease modifying therapy for multiple sclerosis. CONCLUSION: This study underscores the diverse neuroimaging and clinical presentations of patients with TD lesions, and emphasizes the importance of clinical vigilance regarding this rare condition.

Biallelic DDHD2 mutations in patients with adult-onset complex hereditary spastic paraplegia.

OBJECTIVE: Hereditary spastic paraplegias (HSPs) are a group of inherited neurodegenerative disorders characterized by slowly progressive lower limb spasticity and weakness. HSP type 54 (SPG54) is autosomal recessively inherited and caused by mutations in the DDHD2 gene. This study investigated the clinical characteristics and molecular features of DDHD2 mutations in a cohort of Taiwanese patients with HSP. METHODS: Mutational analysis of DDHD2 was performed for 242 unrelated Taiwanese patients with HSP. The clinical, neuroimaging, and genetic features of the patients with biallelic DDHD2 mutations were characterized. A cell-based study was performed to assess the effects of the DDHD2 mutations on protein expression. RESULTS: SPG54 was diagnosed in three patients. Among them, two patients carried compound heterozygous DDHD2 mutations, p.[R112Q];[Y606*] and p.[R112Q];[p.D660H], and the other one was homozygous for the DDHD2 p.R112Q mutation. DDHD2 p.Y606* is a novel mutation, whereas DDHD2 p.D660H and p.R112Q have been reported in the literature. All three patients manifested adult onset complex HSP with additional cerebellar ataxia, polyneuropathy, or cognitive impairment. Brain proton magnetic resonance spectroscopy revealed an abnormal lipid peak in thalamus of all three patients. In vitro studies demonstrated that all the three DDHD2 mutations were associated with a considerably lower DDHD2 protein level. INTERPRETATION: SPG54 was detected in approximately 1.2% (3 of 242) of the Taiwanese HSP cohort. This study expands the known mutational spectrum of DDHD2, provides molecular evidence of the pathogenicity of the DDHD2 mutations, and underlines the importance of considering SPG54 as a potential diagnosis of adult-onset HSP.

Strong immune responses and protection of PcrV and OprF-I mRNA vaccine candidates against Pseudomonas aeruginosa.

Pseudomonas aeruginosa (PA) is a leading cause of hospital-acquired and ventilator-associated pneumonia. The multidrug-resistance (MDR) rate of PA is increasing making the management of PA a global challenge. Messenger RNA (mRNA) vaccines represent the most promising alternative to conventional vaccines and are widely studied for viral infection and cancer immunotherapy while rarely studied for bacterial infections. In this study, two mRNA vaccines encoding PcrV- the key component of the type III secretion system in Pseudomonas and the fusion protein OprF-I comprising outer membrane proteins OprF and OprI were constructed. The mice were immunized with either one of these mRNA vaccines or with the combination of both. Additionally, mice were vaccinated with PcrV, OprF, or the combination of these two proteins. Immunization with either mRNA-PcrV or mRNA-OprF-I elicited a Th1/Th2 mixed or slighted Th1-biased immune response, conferred broad protection, and reduced bacterial burden and inflammation in burn and systemic infection models. mRNA-PcrV induced significantly stronger antigen-specific humoral and cellular immune responses and higher survival rate compared with the OprF-I after challenging with all the PA strains tested. The combined mRNA vaccine demonstrated the best survival rate. Moreover, the mRNA vaccines showed the superiority over protein vaccines. These results suggest that mRNA-PcrV as well as the mixture of mRNA-PcrV and mRNA-OprF-I are promising vaccine candidates for the prevention of PA infection.

Clinical and imaging findings for the evaluation of large Rathke's cleft cysts and cystic craniopharyngiomas.

PURPOSE: Large Rathke's cleft cysts (LRCCs) and cystic craniopharyngiomas (CCPs) arise from the same embryological origin and may have similar MR presentations. However, the two tumors have different management strategies and outcomes. This study was designed to evaluate the clinical and imaging findings of LRCCs and CCPs, aiming to evaluate their pretreatment diagnosis and outcomes. METHODS: We retrospectively enrolled 20 patients with LRCCs and 25 patients with CCPs. Both tumors had a maximal diameter of more than 20 mm. We evaluated the patients' clinical and MR imaging findings, including symptoms, management strategies, outcomes, anatomic growth patterns and signal changes. RESULTS: The age of onset for LRCCs versus CCPs was 49.0 ± 16.8 versus 34.2 ± 22.2 years (p = .022); the following outcomes were observed for LRCCs versus CCPs: (1) postoperative diabetes insipidus: 6/20 (30%) versus 17/25 (68%) (p = .006); and (2) posttreatment recurrence: 2/20 (10%) versus 10/25 (40%) (p = .025). The following MR findings were observed for LRCCs versus CCPs: (1) solid component: 7/20 (35%) versus 21/25 (84%) (p = .001); (2) thick cyst wall: 2/20 (10%) versus 12/25 (48%) (p = .009); (3) intracystic septation: 1/20 (5%) versus 8/25 (32%) (p = .030); (4) snowman shape: 18/20 (90%) versus 1/25 (4%) (p < .001); (5) off-midline extension: 0/0 (0%) versus 10/25 (40%) (p = .001); and (6) oblique angle of the sagittal long axis of the tumor: 89.9° versus 107.1° (p = .001). CONCLUSIONS: LRCCs can be differentiated from CCPs based on their clinical and imaging findings, especially their specific anatomical growth patterns. We suggest using the pretreatment diagnosis to select the appropriate surgical approach and thus improve the clinical outcome.

Prevention of in-stent restenosis with drug-eluting balloons in patients with postirradiated carotid stenosis accepting percutaneous angioplasty and stenting.

OBJECTIVE: To investigate the technical safety and outcome of in-stent restenosis (ISR) prevention with drug-eluting balloon (DEB) in patients with postirradiated carotid stenosis (PIRCS) undergoing percutaneous angioplasty and stenting (PTAS). METHODS: Between 2017 and 2021, we prospectively recruited patients with severe PIRCS for PTAS. They were randomly separated into two groups based on endovascular techniques performed with and without DEB. Preprocedural and early postprocedural (within 24 hours) MRI, short-term ultrasonography (6 months after PTAS), and long-term CT angiography (CTA)/MR angiography (MRA), 12 months after PTAS, were performed. Technical safety was evaluated based on periprocedural neurological complications and the number of recent embolic ischemic lesions (REIL) in the treated brain territory on diffusion-weighted imaging of early postprocedural MRI. RESULTS: Sixty-six (30 with and 36 without DEB) subjects were enrolled, with one failure in techniques. For 65 patients in the DEB versus conventional groups, technical neurological symptoms within 1 month (1/29 (3.4%) vs 0/36; P=0.197) and REIL numbers within 24 hours (1.0±2.1 vs 1.3±1.5; P=0.592) after PTAS showed no differences. Peak systolic velocity (PSVs) on short-term ultrasonography was significantly higher in the conventional group (104.13±42.76 vs .81.95±31.35; P=0.023). The degree of in-stent stenosis (45.93±20.86 vs 26.58±8.75; P<0.001) was higher, and there were more subjects (n=8, 38.9% vs 1, 3.4%; P=0.029) with significant ISR (≥ 50%) in the conventional group than in the DEB group on long-term CTA/MRA. CONCLUSIONS: We observed similar technical safety of carotid PTAS with and without DEBs. The number of cases of significant ISR were fewer and the degree of stenosis of ISR was less in primary DEB-PTAS of PIRCS than for conventional PTAS in the 12-month follow-up.

The Mature COC Promotes the Ampullary NPPC Required for Sperm Release from Porcine Oviduct Cells.

Porcine spermatozoa are stored in the oviductal isthmus after natural mating, and the number of spermatozoa is increased in the oviductal ampulla when the mature cumulus-oocyte complexes (COCs) are transferred into the ampulla. However, the mechanism is unclear. Herein, natriuretic peptide type C (NPPC) was mainly expressed in porcine ampullary epithelial cells, whereas its cognate receptor natriuretic peptide receptor 2 (NPR2) was located on the neck and the midpiece of porcine spermatozoa. NPPC increased sperm motility and intracellular Ca2+ levels, and induced sperm release from oviduct isthmic cell aggregates. These actions of NPPC were blocked by the cyclic guanosine monophosphate (cGMP)-sensitive cyclic nucleotide-gated (CNG) channel inhibitor l-cis-Diltiazem. Moreover, porcine COCs acquired the ability to promote NPPC expression in the ampullary epithelial cells when the immature COCs were induced to maturation by epidermal growth factor (EGF). Simultaneously, transforming growth factor-ß ligand 1 (TGFB1) levels were dramatically increased in the cumulus cells of the mature COCs. The addition of TGFB1 promoted NPPC expression in the ampullary epithelial cells, and the mature COC-induced NPPC was blocked by the transforming growth factor-ß type 1 receptor (TGFBR1) inhibitor SD208. Taken together, the mature COCs promote NPPC expression in the ampullae via TGF-ß signaling, and NPPC is required for the release of porcine spermatozoa from the oviduct isthmic cells.

Clinical and genetic characterization of NIPA1 mutations in a Taiwanese cohort with hereditary spastic paraplegia.

OBJECTIVE: NIPA1 mutations have been implicated in hereditary spastic paraplegia (HSP) as the cause of spastic paraplegia type 6 (SPG6). The aim of this study was to investigate the clinical and genetic features of SPG6 in a Taiwanese HSP cohort. METHODS: We screened 242 unrelated Taiwanese patients with HSP for NIPA1 mutations. The clinical features of patients with a NIPA1 mutation were analyzed. Minigene-based splicing assay, RT-PCR analysis on the patients' RNA, and cell-based protein expression study were utilized to assess the effects of the mutations on splicing and protein expression. RESULTS: Two patients were identified to carry a different heterozygous NIPA1 mutation. The two mutations, c.316G>A and c.316G>C, are located in the 3' end of NIPA1 exon 3 near the exon-intron boundary and putatively lead to the same amino acid substitution, p.G106R. The patient harboring NIPA1 c.316G>A manifested spastic paraplegia, epilepsy and schizophrenia since age 17 years, whereas the individual carrying NIPA1 c.316G>C had pure HSP since age 12 years. We reviewed literature and found that epilepsy was present in multiple individuals with NIPA1 c.316G>A but none with NIPA1 c.316G>C. Functional studies demonstrated that both mutations did not affect splicing, but only the c.316G>A mutation was associated with a significantly reduced NIPA1 protein expression. INTERPRETATION: SPG6 accounted for 0.8% of HSP cases in the Taiwanese cohort. The NIPA1 c.316G>A and c.316G>C mutations are associated with adolescent-onset complex and pure form HSP, respectively. The different effects on protein expression of the two mutations may be associated with their phenotypic discrepancy.

Acute Effects of Static Stretching Combined with Vibration and Nonvibration Foam Rolling on the Cardiovascular Responses and Functional Fitness of Older Women with Prehypertension.

We compared the effects of three warm-up protocols (static stretching (SS), static stretching with vibration foam rolling (SS + VFR), and static stretching with nonvibration foam rolling (SS + FR) on the blood pressure and functional fitness performance in older women with prehypertension. Thirteen older women went through different protocols in separate visits, and their systolic (SBP) and diastolic (DBP) blood pressure, heart rate, mean arterial pressure, brachial pulse pressure (BPP), functional fitness test (back scratch (BS), chair-sit-and-reach, 30 s arm curl (AC), 30 s chair stand, 2 min step, 8-foot up and go), and single-leg standing balance (SLB) were recorded. The SBP and BPP were significantly higher after SS and SS + VFR than after SS + FR. Both SS + FR and SS + VFR significantly improved the 2 min step, when compared with SS. Additionally, SS + VFR significantly improved the BS and AC performance. However, compared with SS and SS + FR, SS + VFR significantly reduced the SLB performance. Therefore, SS + FR may be a better warm-up protocol for older women in maintaining blood pressure. On the other hand, even though SS + VFR induced superior shoulder flexibility, aerobic endurance, and arm strength, it could impair balance.

Investigating KIF1A mutations in a Taiwanese cohort with hereditary spastic paraplegia.

BACKGROUND: Hereditary spastic paraplegia (HSP) is a heterogeneous group of inherited neurodegenerative disorders characterized by slowly progressive lower limbs spasticity and weakness. HSP type 30 (SPG30) is a HSP subtype caused by mutations in the kinesin family member 1A gene (KIF1A) and could be either autosomal dominantly or recessively inherited. The aim of this study was to investigate the clinical and genetic features of KIF1A mutations in a Taiwanese HSP cohort. METHODS: Mutational analysis of KIF1A was performed in 242 unrelated Taiwanese patients of Han Chinese ethnicity with clinically suspected HSP using targeted resequencing panel covering the entire coding regions of KIF1A. Clinical, electrophysiological and neuroimaging features of the HSP patients carrying a KIF1A mutation were characterized. RESULTS: Three different KIF1A mutations were identified in three patients with autosomal dominantly inherited HSP. Among them, KIF1A p.E19K was a novel mutation. The patient harboring KIF1A p.G321D presented with pure HSP, while the individuals carrying KIF1A p.E19K or p.R316Q manifested complex HSP with additional axonal sensorimotor polyneuropathy. The patients carrying KIF1A p.R316Q also had thoracic cord atrophy, thin corpus callosum and white matter hyperintensity. CONCLUSION: SPG30 accounts for 1.2% (3/242) of patients in the Taiwanese HSP cohort, suggesting that it is an uncommon HSP subtype in Taiwan. This study delineates the clinical and genetic features of SPG30 in Taiwan and provides useful information for the diagnosis and management of SPG30, especially in patients of Han Chinese descent.

Influence of angioplasty and stenting on intracranial artery stenosis: preliminary results of high-resolution vessel wall imaging evaluation.

OBJECTIVES: To investigate whether the imaging changes on high-resolution vessel wall imaging (HR-VWI) in patients before and after percutaneous transluminal angioplasty and stenting (PTAS) contribute to predicting the clinical outcome. METHODS: The study included 24 severe intracranial artery stenosis (SICAS) patients undergoing PTAS with Wingspan Stent between 2018 and 2020 and had a 1-year follow-up. Three HR-VWI sessions (preprocedural, early [within 24 h], and delayed postprocedural [134.7 ± 27.1 days)]) in each subject were performed with 3-Tesla MRI. We evaluated periprocedural HR-VWI changes in patients with and without recurrent cerebral ischemic symptoms (RCIS) within 1-year follow-up. RESULTS: On CE-T1WI of the patients without RCIS, a significant decrease in enhanced area was observed on early postprocedural (0.04 ± 0.02 cm2, p = 0.001) and delayed postprocedural (0.04 ± 0.02 cm2; p = 0.001) HR-VWI compared to preprocedural (0.07 ± 0.02 cm2) HR-VWI. Patients with RCIS demonstrated no significant loss of enhanced area on CE-T1WI of early postprocedural HR-VWI (p = 0.180). Significant decreases in calibrated T1 signals were observed in both presence (1.77 ± 0.70 vs. 0.79 ± 0.52; p = 0.018) and absence (1.42 ± 0.62 vs. 0.83 ± 0.40; p = 0.001) of RCIS in early postprocedural HR-VWI. CONCLUSION: The preliminary results showed the presence of reduced contrast enhancement immediately after PTAS may indicate less recurrent stroke events within 1 year. Further studies are necessary to confirm the phenomena in a longer observation period. KEY POINTS: • Early postprocedural high-resolution vessel imaging (HR-VWI) within 24 h can effectively predict a 1-year outcome following intracranial stenting. • For stenotic lesions after stenting without reduced contrast enhancement on HR-VWI within 24 h may need closer clinical surveillance for potentially higher risk of stroke events within 1 year.

The c-di-GMP Phosphodiesterase PipA (PA0285) Regulates Autoaggregation and Pf4 Bacteriophage Production in Pseudomonas aeruginosa PAO1.

In Pseudomonas aeruginosa PAO1, 41 genes encode proteins predicted to be involved in the production or degradation of c-di-GMP, a ubiquitous secondary messenger that regulates a variety of physiological behaviors closely related to biofilm and aggregate formation. Despite extensive effort, the entire picture of this important signaling network is still unclear, with one-third of these proteins remaining uncharacterized. Here, we show that the deletion of pipA, which produces a protein containing two PAS domains upstream of a GGDEF-EAL tandem, significantly increased the intracellular c-di-GMP level and promoted the formation of aggregates both on surfaces and in planktonic cultures. However, this regulatory effect was not contributed by either of the two classic pathways modulating biofilm formation, exopolysaccharide (EPS) overproduction or motility inhibition. Transcriptome sequencing (RNA-Seq) data revealed that the expression levels of 361 genes were significantly altered in a ΔpipA mutant strain compared to the wild type (WT), indicating the critical role of PipA in PAO1. The most remarkably downregulated genes were located on the Pf4 bacteriophage gene cluster, which corresponded to a 2-log reduction in the Pf4 phage production in the ΔpipA mutant. The sizes of aggregates in ΔpipA cultures were affected by exogenously added Pf4 phage in a concentration-dependent manner, suggesting the quantity of phage plays a part in regulating the formation of aggregates. Further analysis demonstrated that PipA is highly conserved across 83 P. aeruginosa strains. Our work therefore for the first time showed that a c-di-GMP phosphodiesterase can regulate bacteriophage production and provided new insights into the relationship between bacteriophage and bacterial aggregation. IMPORTANCE The c-di-GMP signaling pathways in P. aeruginosa are highly organized and well coordinated, with different diguanylate cyclases and phosphodiesterases playing distinct roles in a complex network. Understanding the function of each enzyme and the underlying regulatory mechanisms not only is crucial for revealing how bacteria decide the transition between motile and sessile lifestyles, but also greatly facilitates the development of new antibiofilm strategies. This work identified bacteriophage production as a novel phenotypic output controlled transcriptionally by a phosphodiesterase, PipA. Further analysis suggested that the quantity of phage may be important in regulating autoaggregation, as either a lack of phage or overproduction was associated with higher levels of aggregation. Our study therefore extended the scope of c-di-GMP-controlled phenotypes and discovered a potential signaling circuit that can be target for biofilm treatment.

Pseudomonas aeruginosa modulates alginate biosynthesis and type VI secretion system in two critically ill COVID-19 patients.

BACKGROUND: COVID-19 pneumonia has caused huge impact on the health of infected patients and associated with high morbidity and mortality. Shift in the lung microbial ecology upon such viral infection often worsens the disease and increases host susceptibility to superinfections. Bacterial superinfection contributes to the aggravation of COVID-19 and poses a great challenge to clinical treatments. An in-depth investigation on superinfecting bacteria in COVID-19 patients might facilitate understanding of lung microenvironment post virus infections and superinfection mechanism. RESULTS: We analyzed the adaptation of two pairs of P. aeruginosa strains with the same MLST type isolated from two critical COVID-19 patients by combining sequencing analysis and phenotypic assays. Both P. aeruginosa strains were found to turn on alginate biosynthesis and attenuate type VI secretion system (T6SS) during short-term colonization in the COVID-19 patients, which results in excessive biofilm formation and virulence reduction-two distinct markers for chronic infections. The macrophage cytotoxicity test and intracellular reactive oxygen species measurement confirmed that the adapted P. aeruginosa strains reduced their virulence towards host cells and are better to escape from host immune clearance than their ancestors. CONCLUSION: Our study suggests that SARS-CoV-2 infection can create a lung environment that allow rapid adaptive evolution of bacterial pathogens with genetic traits suitable for chronic infections.

Psl-Dependent Cooperation Contributes to Drug Resistance of Pseudomonas aeruginosa in Dual-Species Biofilms with Acinetobacter baumannii.

Co-infection of Pseudomonas aeruginosa (Pa) and Acinetobacter baumannii (Ab) is frequently observed in intensive care unit (ICU) patients but difficult to eliminate. Current clinical practice based on microbial population characterization and single-species-based antibiotic resistance profiling has ignored the potential interspecies interactions, which might lead to novel drug-resistance phenotypes. Here, we investigated the impacts of interspecies interactions on antibiotic therapies by establishing a Pa and Ab dual-species biofilm model. Our data showed that antibiotic exposure would reshape the community compositions of dual-species biofilms, and those of the extracellular polymeric substance (EPS) matrix of Pa, Psl exopolysaccharide in particular, promoted its interactions with Ab against imipenem stress. We further found other EPS structural fiber-eDNA contributed to the Psl-dependent dual-species biofilm stability under antibiotic treatment. Thus, targeting the EPS structural fibers such as Psl and extracellular DNA (eDNA) is a potent strategy for controlling polymicrobial biofilm related infections.

Treatment response, risk of relapse and clinical characteristics of Taiwanese patients with neuromyelitis optica spectrum disorder.

BACKGROUND/PURPOSE: The long-term disease course and efficacy of maintenance therapies have rarely been investigated in Asian patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: Medical records of patients fulfilling the 2015 International Consensus Diagnostic Criteria for NMOSD at three medical centers in Taiwan were systematically analyzed. Linear regression analysis was performed to investigate factors related to annualized relapse rate (ARR); survival analysis was used to estimate the relapse-free intervals among therapies. RESULTS: A total of 557 relapses affecting 648 regions (202 optic neuritis, 352 acute myelitis, and 94 brain syndromes) in 204 patients were analyzed during a follow-up period of 69.5 months (range, 1-420). Up to 36.1% of myelitis-onset patients and 24.0% of optic neuritis-onset patients exhibited a limited form disease, defined as having one or more relapses confined to the same region. The median ARR was significantly lower in patients with limited form disease than those with relapses involving multiple regions (0.30 vs. 0.47, respectively). An older age at disease onset was associated with a lower ARR (p = 0.023). Kaplan-Meier analysis showed that the estimated time (months) to next relapse was longest in rituximab-treatment group (58.0 ± 13.2), followed by immunosuppressant (48.5 ± 4.8) or prednisone (29.6 ± 4.6) groups, and shortest in those without maintenance therapy (27.6 ± 4.2) (p = 8.1 × 10-7). CONCLUSION: Limited form disease and older age at disease onset are associated with a lower relapse rate in NMOSD. Compared to no maintenance therapy, rituximab and immunosuppressant significantly reduce the relapse risks.