Abnormal multimodal neuroimaging patterns associated with social deficits in male autism spectrum disorder.

Atypical social impairments (i.e., impaired social cognition and social communication) are vital manifestations of autism spectrum disorder (ASD) patients, and the incidence rate of ASD is significantly higher in males than in females. Characterizing the atypical brain patterns underlying social deficits of ASD is significant for understanding the pathogenesis. However, there are no robust imaging biomarkers that are specific to ASD, which may be due to neurobiological complexity and limitations of single-modality research. To describe the multimodal brain patterns related to social deficits in ASD, we highlighted the potential functional role of white matter (WM) and incorporated WM functional activity and gray matter structure into multimodal fusion. Gray matter volume (GMV) and fractional amplitude of low-frequency fluctuations of WM (WM-fALFF) were combined by fusion analysis model adopting the social behavior. Our results revealed multimodal spatial patterns associated with Social Responsiveness Scale multiple scores in ASD. Specifically, GMV exhibited a consistent brain pattern, in which salience network and limbic system were commonly identified associated with all multiple social impairments. More divergent brain patterns in WM-fALFF were explored, suggesting that WM functional activity is more sensitive to ASD's complex social impairments. Moreover, brain regions related to social impairment may be potentially interconnected across modalities. Cross-site validation established the repeatability of our results. Our research findings contribute to understanding the neural mechanisms underlying social disorders in ASD and affirm the feasibility of identifying biomarkers from functional activity in WM.

Evaluation of clinical characteristics and risk factors associated with Chlamydia psittaci infection based on metagenomic next-generation sequencing.

INTRODUCTION: Psittacosis is a zoonosis caused by Chlamydia psittaci, the clinical manifestations of Psittacosis range from mild illness to fulminant severe pneumonia with multiple organ failure. This study aimed to evaluate the clinical characteristics of Chlamydia psittaci infection diagnosed based on metagenomic next-generation sequencing(mNGS), as well as the risk factors affecting the progress of Chlamydia psittaci infection, in order to improve the effect of therapeutics. METHODS: We retrospectively analyzed the clinical data of patients infected with chlamydia psittaci in the First Affiliated Hospital of Nanchang University from January 2021 to December 2021. The patient's past medical history, clinical manifestations, laboratory examinations, chest CT results, treatment status, and prognosis data were collected. we also investigated both the pathogenic profile characteristics and the lower respiratory tract microbiota of patients with Chlamydia psittaci pneumonia using mNGS. RESULTS: All cases of Chlamydia psittaci in our research have been confirmed by mNGS. Among 46 cases of Chlamydia psittaci pneumonia, Poultry exposure was reported in 35 cases. In severe cases of Chlamydia psittaci pneumonia, Neutrophils, Procalcitonin (PCT), Lactate Dehydrogenase (LDH), Hydroxybutyrate Dehydrogenase (HBDH), Creatine Kinase Isoenzymes-B (CK-MB) and D-Dimer levels were remarkably higher than that of non-severe cases, except for lymphocytes (all P < 0.05). Chest CT scans showed Bilateral (77.8%), multiple lobar lungs (85.2%), pleural effusions (44.4%) involvement in those suffering from severe Chlamydia psittaci pneumonia, whereas its incidence was 0%, 21.1% and 10.5% in non-severe patients, respectively (P < 0.05). Multivariate analysis revealed that higher lymphocyte concentrations (OR 0.836, 95% CI 0.714-0.962, P = 0.041) were the only protective factor for survival. mNGS results indicated that 41.3% of patients (19/46) had suspected coinfections with a coinfection rate of 84.2% (16/19) in the severe group, much higher than that in the non severe group (p < 0.05). No significantly different profiles of lower respiratory tract microbiota diversity were found between non severe group and severe group. CONCLUSION: A history of poultry exposure in patients can serve as an important basis for diagnosing Chlamydia psittaci pneumonia, and patients with severe Chlamydia psittaci pneumonia are more likely to develop elevated inflammatory biomarkers as well as elevated cardiac markers. Higher lymphocyte concentrations are protective factors associated with severe C. psittaci pneumonia. The higher proportion of patients with coinfections in our study supports the use of mNGS for comprehensive early detection of respiratory infections in patients with C. psittaci pneumonia.

Acute necrotizing encephalopathy in adult patients with influenza: a case report and review of the literature.

The neurological complications of influenza affect mainly the pediatric Asian population. In the category of influenza-associated encephalopathy, acute necrotizing encephalopathy (ANE) is a rapidly progressive and fulminant brain disorder associated with significant neurological sequelae and mortality. To date, only a few adult cases of influenza-associated ANE have been reported. We describe a 44-year-old woman who presented with rapid progression of consciousness impairment and recurrent generalized convulsions. Influenza was diagnosed three days prior to presentation, and infection with influenza A (H3N2) pdm09 was subsequently confirmed. A diagnosis of ANE was made based on the presence of characteristic brain MRI findings, the exclusion of central nervous system infection, and an elevated serum interleukin-6 level. Pulse steroid therapy followed by tocilizumab was initiated, which led to clinical stabilization and improvement. Genetic testing revealed that the patient carried heterozygous human leukocyte antigen DQB1 03:03 and DRB1 09:01 genotypes. An analysis of the adult cases of influenza-associated ANE in the literature and the present case revealed a wide range of ages (22-71 years), a short interval (median 3 days) between the clinical onset of influenza and ANE, and a high overall mortality rate (32%). The thalamus was the most frequent (91%) location of the lesions. Our report highlights the importance of identifying this devastating but treatable neurological complication of influenza in adults, especially those of Asian descent. As a cytokine storm is the most accepted pathogenic mechanism for ANE, cytokine-directed therapies may be promising treatments for which further investigation is warranted.

High Tibial Osteotomy With Medial Meniscal Posterior Root Tear Reconstruction Yields Improved Radiographic and Functional Outcomes and Healing Rates Compared With Osteotomy Alone.

PURPOSE: To compare preoperative and postoperative clinical and radiologic outcomes between patients undergoing high tibial osteotomy (HTO) with medial meniscal posterior root tear (MMPRT) reconstruction using gracilis tendon graft and those undergoing HTO without MMPRT reconstruction. METHODS: Patients with MMPRTs who underwent HTO between January 2018 and December 2021 with minimum 2-year follow-up were included. All patients were divided into 2 groups based on whether they underwent meniscal root reconstruction with tendon graft: HTO alone (33 cases) and HTO with MMPRT reconstruction (21 cases). Clinical evaluation included the Lysholm score, International Knee Documentation Committee (IKDC) score, and visual analog scale (VAS) score. Functional recovery and radiologic outcomes of the knees were evaluated at the latest follow-up. Meniscal root healing rates and medial meniscal extrusion according to a second magnetic resonance imaging reading were compared between the 2 groups at the latest follow-up. RESULTS: The results showed statistically significant improvements in the postoperative Lysholm score, IKDC score, and VAS score in both groups at the latest follow-up (P < .001). Analysis of the minimal clinically important difference for postoperative outcomes revealed that the percentage of patients who reached the minimal clinically important difference threshold was 100% for the Lysholm score, 100% for the IKDC score, and 100% for the VAS score in the HTO-MMPRT reconstruction group. In comparison, the percentages were 87.9% for the Lysholm score, 90.9% for the IKDC score, and 100% for the VAS score in the HTO-alone group. Additionally, compared with the HTO-alone group, the HTO-MMPRT reconstruction group using gracilis tendon graft showed significantly improved meniscal root healing rates (complete healing, 85.7% vs 45.4% [95% confidence interval, 0.003-0.007]; P = .001) and functional recovery (P < .005) at the final follow-up. Additionally, the HTO-MMPRT reconstruction group showed significantly more improvement in the Kellgren-Lawrence grade (10 of 21 knees vs 6 of 33 knees with improved Kellgren-Lawrence grade, P = .033) and medial meniscal extrusion (2.1 ± 1.0 mm vs 3.1 ± 1.6 mm [95% confidence interval, 0.3-1.7 mm]; P = .007) compared with the HTO-alone group. CONCLUSIONS: HTO with reconstruction of the meniscal root using a tendon graft resulted in improved radiographic and patient-reported outcomes, as well as improved healing rates, compared with HTO alone. LEVEL OF EVIDENCE: Level III, retrospective case-series comparison.

Blood neurofilament light chain as a surrogate marker for dystonia.

BACKGROUND AND PURPOSE: Dystonia is a heterogeneous movement disorder, and it remains unclear whether neurodegeneration is involved. Neurofilament light chain (NfL) is a biosignature of neurodegeneration. We aimed to investigate whether plasma NfL levels were elevated and associated with disease severity in patients with dystonia. METHOD: We enrolled 231 unrelated dystonia patients (isolated dystonia n = 203; combined dystonia n = 28) and 54 healthy controls from movement disorder clinics. Clinical severity was evaluated using the Fahn Marsden Dystonia Rating Scale, the Unified Dystonia Rating Scale, and the Global Dystonia Rating Scale. Blood NfL levels were measured by single-molecule array. RESULTS: Plasma NfL levels were significantly higher in those with generalized dystonia compared to those with focal dystonia (20.1 ± 8.8 vs. 11.7 ± 7.2 pg/mL; p = 0.01) or controls (p < 0.01), while the level was comparable between the focal dystonia group and controls (p = 0.08). Furthermore, the dystonia combined with parkinsonism group had higher NfL levels than the isolated dystonia group (17.4 ± 6.2 vs. 13.5 ± 7.5 pg/mL; p = 0.04). Notably, whole-exome sequencing was performed in 79 patients and two patients were identified as having likely pathogenic variants: one had a heterozygous c.122G>A (p.R41H) variant in THAP1 (DYT6) and the other carried a c.1825G>A (p.D609N) substitution in ATP1A3 (DYT12). No significant correlation was found between plasma NfL levels and dystonia rating scores. CONCLUSION: Plasma NfL levels are elevated in patients with generalized dystonia and dystonia combined with parkinsonism, suggesting that neurodegeneration is involved in the disease process of this subgroup of patients.

Younger patients, lower BMI, complete meniscus root healing, lower HKA degree and shorter preoperative symptom duration were the independent risk factors correlated with the good correction of MME in patients with repaired MMPRTs.

PURPOSE: To evaluate the clinical and radiological outcomes of arthroscopically assisted tendon graft anatomic reinforced reconstruction of the medial meniscus posterior root tears (MMPRTs) and identify relevant factors affecting the correction of medial meniscal extrusion (MME). METHODS: Fifty-three MMPRTs patients who underwent arthroscopically assisted tendon graft reconstruction of the meniscal root between 2018 and 2020 were evaluated retrospectively. the patients were divided into 2 groups according to the correction of MME (maintained MME group: 32 cases vs. increased MME group: 21 cases). The clinical and radiological outcomes of arthroscopically assisted tendon graft reconstruction of the meniscal root, including postoperative correction of MME and functional recovery of the knee were assessed in this study, and potential independent risk factors that could influence the correction of MME were also evaluated. RESULTS: The functional recovery of the knee was significantly improved at the end of follow-up (P < 0.001; respectively), furthermore, a comparison of the final functional outcomes between the groups showed that the mean Lysholm score and IKDC score of the maintained MME group were significantly improved than those of increased MME group. 60.4% had good correction of MME, and patients with complete healing had better extrusion correction than those with partial healing and non-healing. Binary logistic regression models analysis indicated that the age (OR = 1.053, P = 0.048), BMI (OR = 1.376, P = 0.004), meniscus root healing status (OR = 7.701, P = 0.005), HKA degree (OR = 1.891, P = 0.011) and preoperative symptom duration (OR = 1.055, P = 0.013) were the independent risk factors correlated with correction of MME. Additionally, the ROC curve demonstrated the cut-off values of the Age, BMI, HKA degree and preoperative symptom duration were 46.0 years, 22.5 kg/m2, 3.2° and 9.5 months, respectively, CONCLUSIONS: The arthroscopically assisted tendon graft anatomic reinforced reconstruction of the meniscal root showed clinical improvement and prevented the progression of postoperative MME. Additionally, younger patients, lower BMI, complete meniscus root healing, lower HKA degree and shorter preoperative symptom duration were the independent risk factors correlated with the good correction of MME in patients with repaired MMPRTs. LEVEL OF EVIDENCE: Level IV.

The Genetics of Primary Familial Brain Calcification: A Literature Review.

Primary familial brain calcification (PFBC), also known as Fahr's disease, is a rare inherited disorder characterized by bilateral calcification in the basal ganglia according to neuroimaging. Other brain regions, such as the thalamus, cerebellum, and subcortical white matter, can also be affected. Among the diverse clinical phenotypes, the most common manifestations are movement disorders, cognitive deficits, and psychiatric disturbances. Although patients with PFBC always exhibit brain calcification, nearly one-third of cases remain clinically asymptomatic. Due to advances in the genetics of PFBC, the diagnostic criteria of PFBC may need to be modified. Hitherto, seven genes have been associated with PFBC, including four dominant inherited genes (SLC20A2, PDGFRB, PDGFB, and XPR1) and three recessive inherited genes (MYORG, JAM2, and CMPK2). Nevertheless, around 50% of patients with PFBC do not have pathogenic variants in these genes, and further PFBC-associated genes are waiting to be identified. The function of currently known genes suggests that PFBC could be caused by the dysfunction of the neurovascular unit, the dysregulation of phosphate homeostasis, or mitochondrial dysfunction. An improved understanding of the underlying pathogenic mechanisms for PFBC may facilitate the development of novel therapies.

mTORC1/C2 regulate spermatogenesis in Eriocheir sinensis via alterations in the actin filament network and cell junctions.

Spermatogenesis is a finely regulated process of germ cell proliferation and differentiation that leads to the production of sperm in seminiferous tubules. Although the mammalian target of rapamycin (mTOR) signaling pathway is crucial for spermatogenesis in mammals, its functions and molecular mechanisms in spermatogenesis remain largely unknown in nonmammalian species, particularly in Crustacea. In this study, we first identified es-Raptor (the core component of mTOR complex 1) and es-Rictor (the core component of mTOR complex 2) from the testis of Eriocheir sinensis. Dynamic localization of es-Raptor and es-Rictor implied that these proteins were indispensable for the spermatogenesis of E. sinensis. Furthermore, es-Raptor and es-Rictor knockdown results showed that the mature sperm failed to be released, causing almost empty lumens in the testis. We investigated the reasons for these effects and found that the actin-based cytoskeleton was disrupted in the knockdown groups. In addition, the integrity of the testis barrier (similar to the blood-testis barrier in mammals) was impaired and affected the expression of cell junction proteins. Further study revealed that es-Raptor and es-Rictor may regulate spermatogenesis via both mTORC1- and mTORC2-dependent mechanisms that involve es-rpS6 and es-Akt/es-PKC, respectively. Moreover, to explore the testis barrier in E. sinensis, we established a cadmium chloride (CdCl2)-induced testis barrier damage model as a positive control. Morphological and immunofluorescence results were similar to those of the es-Raptor and es-Rictor knockdown groups. Altogether, es-Raptor and es-Rictor were important for spermatogenesis through maintenance of the actin filament network and cell junctions in E. sinensis.

Medial meniscus posterior root tear reconstructed with gracilis autograft improve healing rate and patient reported outcome measures.

BACKGROUND: Many surgeries have not reversed or prevented progressive symptomatic knee arthritis, and there is no consensus regarding the ideal repair or reconstruction technique for meniscal root treatment. Additionally, there is a lack of studies comparing the clinical efficacy evaluation of different repair techniques. The aim of the present study is to compare the clinical efficacy and healing rates of meniscus root in the treatment of medial meniscus posterior root tear (MMPRT) with the arthroscopically assisted meniscus root reconstruction with gracilis autograft and transtibial pull-out technique. METHODS: Patients with MMPRT (type II) who received treatment of posterior meniscus root attachment point through the tibial tunnel between January 2018 and April 2019 were included in this study. Patients were divided into 2 groups (arthroscopically assisted gracilis autograft reconstruction technique: 29 cases; transtibial pull-out technique group: 35 cases) according to the different treatment methods. The mean follow-up period was 26.9 ± 2.3 months. The demographics, functional recovery of the knee, and meniscus root healing rates (assessed using knee magnetic resonance imaging (MRI) at the final follow-up) were compared between the two groups. RESULTS: There was a statistically significant improvement in the Lysholm score, international knee documentation committee (IKDC) score, and visual analogue scale (VAS) score (P < 0.001 in both groups). Additionally, compared with the transtibial pull-out repair group, the arthroscopically assisted reconstruction with gracilis autograft showed significant improvement in the meniscus root healing rates, Lysholm score, and IKDC score at the end of follow-up (P < 0.05). CONCLUSIONS: Compared with the transtibial pull-out technique, the arthroscopically assisted meniscus root reconstruction with gracilis autograft was advantageous for treating these patients with superior clinical outcome and higher meniscus root healing rates. LEVEL OF EVIDENCE: Level III.

Comparative analysis of arthroscopic-assisted Tight-rope technique and clavicular hook plate fixation in the treatment of Neer type IIB distal clavicle fractures.

BACKGROUND: The aim of the present study was to compare the clinical efficacy of arthroscopic-assisted fixation using the Tight-rope system and clavicular hook plate fixation in the treatment of Neer IIB distal clavicle fractures. METHODS: We enrolled 48 consecutive patients with Neer IIB distal clavicle fractures who were treated at our institution from February 2016 and August 2020. These patients were divided into 2 groups based on the fixation method (16 cases with Tight-rope system and 32 cases with clavicular hook plate), and demographics and clinical characteristics of patients in different groups were compared. RESULTS: All 48 patients had functional outcome scores of the affected shoulder available at a mean of 23.8 ± 5.1 months, and there was a statistically significant improvement in the constant score, American shoulder and elbow surgeons (ASES) score, visual analogue scale (VAS) score at the end of follow-up (p < 0.001 respectively). However, the smaller length of skin incision, less estimated blood loss and shorter hospital stay were detected in the Tight-rope technique group patients than those of clavicular hook plate group patients (p < 0.001, respectively). Furthermore, the constant score, ASES score and VAS score were significantly improved in the Tight-rope technique group patients than those of clavicular hook plate group patients (p < 0.05, respectively). CONCLUSIONS: Both Tight-rope technique and clavicular hook plate fixation can provide satisfactory clinical and radiological results in the treatment of distal clavicular Neer IIB fracture. However, arthroscopic-assisted fixation using the Tight-rope technique showed better results in terms of length of hospital stay, surgical trauma, clinical scores, and diagnose and treat concomitant glenohumeral pathologies. LEVELS OF EVIDENCE: III, Case-control study Retrospective comparative study.

Investigating DYT1 in a Taiwanese dystonia cohort.

BACKGROUND/PURPOSE: A heterozygous three-nucleotide (GAG) in-frame deletion in the TOR1A gene causes the rare disease, dystonia (DYT1), which typically presents as focal limb dystonia during adolescence, then spreads to other limbs. This study investigated the frequency and clinical features of DYT1 in a Taiwanese dystonia cohort. METHODS: We performed targeted next generation sequencing in 318 patients with primary dystonia. We identified one DYT1 family with various types of dystonia, and we described the clinical presentations observed in this family during a 30-year follow-up. We compared the clinical characteristics to those reported in previous studies on DYT1 from 2000 to 2020. RESULTS: Among 318 patients, we identified only one DYT1 patient (0.3%) with an autosomal dominant family history of dystonia. The proband was a 43-year-old man that experienced progressive onset of focal lower limb dystonia from age 11 years. The disease spread caudal-rostrally to the upper limbs and cervical muscles. Prominent cervical dystonia was noted during follow-up, which was an atypical presentation of DYT1. Clinical assessments of other family members showed intrafamily variability. The proband's father and an affected sibling demonstrated only mild right-hand writer's cramp. A systematic review of previously reported DTY1 cases showed that Asian patients had a higher frequency of cervical dystonia (44.8%) than groups of Ashkenazi Jews (35%) and Non-Jewish Caucasians (30.5%) (P = 0.04). CONCLUSION: Our findings revealed that DYT1 is rare in a Taiwanese dystonia cohort. The presentation of marked cervical dystonia could be the main feature of Asian patients with DYT1.

Re-evaluating the necessity of routine laboratory tests after high tibial osteotomy surgery.

BACKGROUND: To assess the utility of routine postoperative laboratory tests for patients undergoing high tibial osteotomy (HTO) surgery. METHODS: The associations between clinical risk factors and postoperative clinical treatment were analyzed. Additionally, a logistic regression analysis was performed to detect independent risk factors for patients requiring postoperative clinical treatment. RESULTS: A total of 482 patients with symptomatic isolated medial compartment osteoarthritis from January 2015 to May 2020 were included in the present study and underwent examination by the full set of postoperative laboratory tests within 3 days after HTO surgery. However, only a small proportion of the patients with anemia (3.9 %), hypoalbuminemia (4.1 %), and abnormal serum potassium levels (3.5 %) required clinical intervention after surgery. Binary logistic regression analysis showed that the body mass index (BMI), preoperative hemoglobin level, estimated blood loss and operative duration were independent risk factors for postoperative blood transfusion in patients who underwent HTO surgery, and factors associated with albumin supplementation were female sex and preoperative albumin level. In addition, these results indicated that preoperative potassium was potential risk factor for patients who required potassium supplementation postoperatively. CONCLUSIONS: Based on the analysis, we conclude that routinely ordering postoperative laboratory tests after HTO surgery is unnecessary. However, for patients with identified risk factors, routine postoperative laboratory tests are still needed.

KIF3A regulates the Wnt/ß-catenin pathway via transporting ß-catenin during spermatogenesis in Eriocheir sinensis.

The Wnt/ß-catenin pathway participates in many important physiological events such as cell proliferation and differentiation in the male reproductive system. We found that Kinesin-2 motor KIF3A is highly expressed during spermatogenesis in Eriocheir sinensis; it may potentially promote the intracellular transport of cargoes in this process. However, only a few studies have focused on the relationship between KIF3A and the Wnt/ß-catenin pathway in the male reproductive system of decapod crustaceans. In this study, we cloned and characterized the CDS of ß-catenin in E. sinensis for the first time. Fluorescence in situ hybridization and immunofluorescence results showed the colocalization of Es-KIF3A and Es-ß-catenin at the mRNA and the protein level respectively. To further explore the regulatory function of Es-KIF3A to the Wnt/ß-catenin pathway, the es-kif3a was knocked down by double-stranded RNA (dsRNA) in vivo and in primary cultured cells in testes of E. sinensis. Results showed that the expression of es-ß-catenin and es-dvl were decreased in the es-kif3a knockdown group. The protein expression level of Es-ß-catenin was also reduced and the location of Es-ß-catenin was changed from nucleus to cytoplasm in the late stage of spermatogenesis when es-kif3a was knocked down. Besides, the co-IP result demonstrated that Es-KIF3A could bind with Es-ß-catenin. In summary, this study indicates that Es-KIF3A can positively regulate the Wnt/ß-catenin pathway during spermatogenesis and Es-KIF3A can bind with Es-ß-catenin to facilitate the nuclear translocation of Es-ß-catenin.

Recessively-Inherited Adult-Onset Alexander Disease Caused by a Homozygous Mutation in the GFAP Gene.

BACKGROUND: Alexander disease (AxD) is an autosomal-dominant leukodystrophy caused by heterozygous mutations in the glial fibrillary acidic protein (GFAP) gene. OBJECTIVES: The objective of this report is to characterize the clinical phenotype and identify the genetic mutation associated with adult-onset AxD. METHODS: A man presented with progressive unsteadiness since age 16. Magnetic resonance imaging findings revealed characteristic features of AxD. The GFAP gene was screened, and a candidate variant was functionally tested to evaluate causality. RESULTS: A homozygous c.197G > A (p.Arg66Gln) mutation was found in the proband, and his asymptomatic parents were heterozygous for the same mutation. This mutation affected GFAP solubility and promoted filament aggregation. The presence of the wild-type protein rescued mutational effects, consistent with the recessive nature of this mutation. CONCLUSIONS: This study is the first report of AxD caused by a homozygous mutation in GFAP. The clinical implication is while examining patients with characteristic features on suspicion of AxD, GFAP screening is recommended even without a supportive family history. © 2020 International Parkinson and Movement Disorder Society.

Brain hypoperfusion and nigrostriatal dopaminergic dysfunction in primary familial brain calcification caused by novel MYORG variants: case report.

BACKGROUND: Primary familial brain calcification (PFBC) is a rare inherited disease characterized by multiple calcified foci in the brain parenchyma. MYORG is the first gene found to be associated with autosomal recessive PFBC. The precise pathogenic mechanism of neurodegeneration in PFBC remains unclear. The clinical phenotypes of PFBC are variable, and there is no clear correlation between clinical manifestations and radiological and pathological features of calcification. CASE PRESENTATION: Two sisters in a Taiwanese family presented with young-onset Parkinsonism and multifocal dystonia. Their brain CTs showed multiple intracerebral calcifications. The genetic study detected two heterozygous novel variants, c.104 T > A (p.Met35Lys) and c.850 T > C (p.Cys284Arg) in the MYORG gene. In both patients, MR susceptibility weighted images revealed calcification of the deep medullary veins. Tc99m ECD SPECT demonstrated a significant decrease of tracer uptake in the brain cortex and subcortical gray matter. Tc99m TRODAT-1 SPECT revealed decreased tracer uptake in the bilateral striatum. CONCLUSION: Two novel MYORG variants were identified in Taiwanese family members presenting with PFBC. Abnormalities in the brain perfusion and dopamine transporter SPECTs suggest that cerebral ischemia due to extensive calcified vasculopathy, disruption of the basal ganglia-thalamo-cortical circuit, and nigrostriatal dopaminergic dysfunction are plausible pathogenic mechanisms of neurodegeneration in PFBC patients. Further investigation into the correlations between the pathogenicity-implicated imaging findings and the clinical phenotype are recommended.

Self-regulated learning strategies in world's first MOOC in implant dentistry.

BACKGROUND: Massive Open Online Courses (MOOCs) have been often described as a major innovation Higher Education, but their application in the teaching of clinical disciplines is still very limited, while there is a lack of scientific evaluations in this domain. The aim of this study was to investigate learners' behaviours and correlate patterns of Self-Regulated Learning (SRL) with performance and achievement during a MOOC in Implant Dentistry. METHODS: The clickstream data of learners from the first run of the MOOC Implant dentistry by The University of Hong Kong were modelled and quantified based on Zimmerman's SRL model. The data were quantitatively analysed by means of k-means clustering for evidence of five SRL behavioural indicators of student activity. The clusters identified were then correlated with student engagement and learning performance. RESULTS: A total of 7608 individuals enrolled, 5014 engaged (active learners 65.90%), 1277 of them (25.47%) completed the course and 1232 purchased a certificate. Two major groups of learners emerged: Attentive (n = 1433) who were more likely to follow the prescribed pathway in the MOOC and Auditors (n = 3581) who accessed content selectively. There was significantly higher engagement, achievement and completion rates among Attentive than Auditors. Both groups included subcategories (Browser, Digger, Test-driven, Sampler, Persistent) which might reflect different SRL strategies. CONCLUSION: A MOOC in a clinical discipline can achieve high enrolment and completion rates as compared to current benchmarks. There appears to be a wide diversity of learning behaviours among learners, with two however dominant patterns. Learners with a linear learning pathway achieved significantly higher grades and completion rates than those who accessed content irregularly and selectively. Such differences however might be influenced by the demographic and professional background of the learner, as well as their motivation to attending the MOOC. Certain learning behaviours, in particular how learners access content in relation to assessments might be closer related to SRL.

High Drug Loading and Sub-Quantitative Loading Efficiency of Polymeric Micelles Driven by Donor-Receptor Coordination Interactions.

Polymeric micelles are extensively used for the delivery of hydrophobic drugs, which, however, suffer from unsatisfactory drug loading, colloidal uniformity, formulation stability, and drug release. Herein, we demonstrate a convenient strategy to prepare micelles with ultrahigh drug loading via the incorporation of polymer-drug coordination interactions. An amphiphilic copolymer containing pendant phenylboronic acid as electron acceptor unit was synthesized, which afforded donor-acceptor coordination with doxorubicin to obtain micelles with ultrahigh drug loading (∼50%), nearly quantitative loading efficiency (>95%), uniform size, and colloidal stability. Besides, the encapsulated drug can be effectively and selectively released in response to the high reactive oxygen species levels in cancer cells, which potentiated the anticancer efficacy and reduced systemic toxicity. Apart from doxorubicin, the current platform could be extended to other drugs with electron-donating groups (e.g., epirubicin and irinotecan), rendering a simple and robust strategy for enabling high drug loading in polymeric micelles and cancer-specific drug release.

[Motion-in-depth Perception and Static Stereopsis of Patients with Strabismics].

OBJECTIVE: To determine the role of motion-in-depth perception and static stereopsis in strabismics, and factors associated with the perception of motion-in-depth. METHODS: A total of 84 strabismic patients (including 57 intermittent exotropes, 12 constant exotropes and 15 esotropes) and 16 normal controls were recruited. Binocular fusion ability, static stereopsis and motion-in-depth perception were tested using the computer-generated stereoscopic stimuli. The correlations between these tests were analyzed. RESULTS: There was a significant correlation between motion-in-depth perception and static stereopsis in strabismics. Only patients with static stereopsis demonstrated the perception of motion-in-depth. A positive correlation was found between motion-in-depth perception thresholds and static stereopsis in intermittent exotropes. All participants in the control group had motion-in-depth perception and static stereopsis. The participants with stereopsis had significantly lower thresholds than those with strabismus (P<0.01). The perception of motion-in-depth varied with the type of strabismus: 87.7% of the intermittent exotropes exhibited motion-in-depth perception, whereas none of the constant strabismics were able to pass the motion-in-depth perception tests. The perception of motion-in-depth was correlated with the presence of binocular fusion. CONCLUSIONS: Motion-in-depth perception is correlated with static stereopsis in strabismics. The perception of motion-in-depth varies with the type of strabismus: only intermittent exotropes have the perception of motion-in-depth.

Identification of VPS35 p.D620N mutation-related Parkinson's disease in a Taiwanese family with successful bilateral subthalamic nucleus deep brain stimulation: a case report and literature review.

BACKGROUND: Vacuolar protein sorting 35 (VPS35) was recently reported to be a genetic cause for late-onset autosomal dominant Parkinson's disease (PD). However, VPS35 mutations are rarely reported in Asian populations. Herein, we report the first Taiwanese family with the pathogenic VPS35 p.D620N mutation, including one patient treated successfully with subthalamic nucleus deep brain stimulation (STN-DBS). CASE PRESENTATION: A 61-year-old woman presented with progressive left hand resting tremor at the age of 42. Neurological examinations revealed mask face and akinetic-rigidity over left extremities. She showed a good response to levodopa treatment, and her unified Parkinson's disease rating scale (UPDRS) motor scores improved from 42 to 15 under the levodopa equivalent dose of 1435 mg/day. She developed peak-dose dyskinesia and motor fluctuation seven years after the onset of symptoms, and received bilateral STN-DBS at the age of 55. Stimulation led to a marked improvement in her motor symptoms with a 37% improvement in the UPDRS motor score during the OFF period five years after surgery. The patient's mother and three siblings were also diagnosed with PD in their forties, following an autosomal-dominant inheritance pattern. We performed genetic analysis of the proband using a targeted next generation sequencing (NGS) panel covering 17 known PD-causative genes. We identified a pathogenic missense mutation in VPS35 gene, c.1858G > A (p.D620N), in this patient. CONCLUSIONS: This is the first report of the VPS35 p.D620N mutation in a Taiwanese family. Additionally, our report contributes to the current understanding of genetically defined PD patients treated successfully with STN-DBS.