Self-improving dystrophic epidermolysis bullosa with a novel heterozygous missense variant in the COL7A1 gene in a Taiwanese family.

Self-improving dystrophic epidermolysis bullosa (DEB) is a genodermatosis that is inherited autosomal dominantly or recessively, and its clinical symptoms may improve or subside spontaneously. Herein, we report a case of self-improving DEB with COL7A1 p.Gly2025Asp variant. The diagnosis was made through histopathological, electron microscopic examination, and genetic testing. The same variant is also noted on his father, who presents with dystrophic toenails without any blisters. This study highlights that idiopathic nail dystrophy could be linked to congenital or hereditary disease. Furthermore, we conducted a review of the literature on the characteristics of reported cases of self-improving DEB with a personal or family history of nail dystrophy. The results supported our findings that nail dystrophy may be the sole manifestation in some family members. We suggest that individuals suffering from idiopathic nail dystrophy may seek genetic counselling when planning pregnancy to early evaluate the potential risk of hereditary diseases.

Factors Impacting Survival in Patients With Major Burn-Induced Acute Kidney Injury Postrenal Replacement Therapy: A Nationwide Study With 15 Years Follow-Up in Taiwan.

BACKGROUND: Major burn-induced acute kidney injury (AKI) causes extremely high mortality, even though renal replacement therapy (RRT) was thought of as the most efficient treatment. There was scanty research for investigating the characteristic of burn-AKI-RRT patients during intensive care. This study aims to investigate the factors impacting the survival outcomes in those burn-AKI-RRT cases. METHODS: Using the Taiwan National Health Insurance Research Database and its affiliated database, the Registry for Catastrophic Illness Patients, we defined a cohort composed of 171 patients encountering major burn-induced AKI and receiving RRT during burn care for a 15-year observation period. Demographic characteristic, comorbidities, total body surface area (TBSA), major procedures, and complications were analyzed to explore the factors affecting the survival outcomes during acute burn care and 1 year after discharge. RESULTS: Patients who underwent tracheostomy and skin grafting had higher survival rates during acute burn care (tracheostomy: mortality vs survival, 15.7% vs 30.2%; P = 0.0257; skin grafting: mortality vs survival, 57.4% vs 76.2%; P = 0.0134). Multivariate regression analysis showed that tracheostomy group significantly presented with lower mortality risk by 65% (odds ratio [OR], 0.35; P = 0.0372), and subgroup analysis of delaminating follow-up duration showed that patients with tracheostomy had higher overall survival by 22% (90-day postburn mortality: nontracheostomy vs tracheostomy, 58.3% vs 36.3%; adjusted hazards ratio, 0.39; 95% confidence interval, 0.22-0.69; P = 0.0011), especially during postburn first 30 days (adjusted hazards ratio, 0.15; 95% confidence interval, 0.05-0.49; P = 0.0016). Total body surface area did not significantly affect survival; however, mortality risk was significantly higher in those with a larger TBSA (TBSA, ≥80%; OR, 6.48; P = 0.0022; TBSA, 60-79%; OR, 3.12; P = 0.0518; TBSA, 40-59%; OR, 1.88; P = 0.2402; TBSA, 30-39% as reference). CONCLUSIONS: For patients with major burn-induced AKI receiving RRT, tracheostomy and skin grafting may improve survival in the cases living through acute burn stage.

Chromosome-level assembly, genetic and physical mapping of Phalaenopsis aphrodite genome provides new insights into species adaptation and resources for orchid breeding.

The Orchidaceae is a diverse and ecologically important plant family. Approximately 69% of all orchid species are epiphytes, which provide diverse microhabitats for many small animals and fungi in the canopy of tropical rainforests. Moreover, many orchids are of economic importance as food flavourings or ornamental plants. Phalaenopsis aphrodite, an epiphytic orchid, is a major breeding parent of many commercial orchid hybrids. We provide a high-quality chromosome-scale assembly of the P. aphrodite genome. The total length of all scaffolds is 1025.1 Mb, with N50 scaffold size of 19.7 Mb. A total of 28 902 protein-coding genes were identified. We constructed an orchid genetic linkage map, and then anchored and ordered the genomic scaffolds along the linkage groups. We also established a high-resolution pachytene karyotype of P. aphrodite and completed the assignment of linkage groups to the 19 chromosomes using fluorescence in situ hybridization. We identified an expansion in the epiphytic orchid lineage of FRS5-like subclade associated with adaptations to the life in the canopy. Phylogenetic analysis further provides new insights into the orchid lineage-specific duplications of MADS-box genes, which might have contributed to the variation in labellum and pollinium morphology and its accessory structure. To our knowledge, this is the first orchid genome to be integrated with a SNP-based genetic linkage map and validated by physical mapping. The genome and genetic map not only offer unprecedented resources for increasing breeding efficiency in horticultural orchids but also provide an important foundation for future studies in adaptation genomics of epiphytes.

The assessment of Buerger's exercise on dorsal foot skin circulation in patients with vasculopathic diabetic foot ulcer by using wireless near-infrared spectroscope: a cohort prospective study.

The improvement of peripheral circulation is crucial for the care of vasculopathic diabetic foot ulcer (DFU). Near-infrared spectroscopy (NIRS) was used to investigate the effects of Buerger's exercise on dorsal foot skin circulation with novel technique of measuring the absorption difference in wavelength of light between oxy-hemoglobin (HbO2) and deoxy-hemoglobin (HbR). Patients with vasculopathic DFU who could tolerate Buerger's exercise three times a day at home for at least 8 weeks were enrolled (group A). They were divided into two subgroups: without previous percutaneous transluminal angioplasty (PTA) (group A1) vs. with previous PTA (group A2). Wireless NIRS were applied on patients' dorsal foot to assess the peripheral circulation in follow-up clinics. The patients' wound condition, follow-up time, and concentration of HbO2 and total hemoglobin (HbT) before and after exercise rehabilitation program were documented. From May 2015 to February 2016, 14 patients with average age of 70.2 ± 11.2 were enrolled in this study (group A), including eight without previous PTA (group A1), and six with previous PTA (group A2). The concentration of HbO2 and HbT were significantly increased after exercise rehabilitation program training in group A (p = 0.024 in HbO2, p = 0.02 in HbT, n = 14) and group A2 (p = 0.021 in HbO2, p = 0.028 in HbT, n = 6), while the concentration in group A1 were improved with borderline significance after exercise (p = 0.055 in HbO2, p = 0.058 in HbT, n = 8). The majority of the ulcers were either completely healed (11/14 = 78.57%) or improving (3/14 = 21.43%). Buerger's exercise improved the peripheral circulation and wound condition in patients with vasculopathic DFU. The wireless apparatus is a novel and efficient tool to monitor rehabilitation program.

The Predictive Factors Associated With Comorbidities for Treatment Response in Outpatients With King Classification III Diabetes Foot Ulcers.

OBJECTIVE: The aim of this study is to investigate the preexisting predictive factors associated with comorbidities for diabetic foot ulcer (DFU) in King classification III at an outpatient clinic. METHOD: This prospective study included 100 patients with DFU in King classification III treated at outpatient clinics in Chiayi Chang Gung Memorial Hospital from January 2011 to December 2011. The least follow-up time was 1 year. Medical documentations were in respect of patient's baseline characteristics, associated history, presence of comorbidities, follow-up time, and condition of wounds. Patients were divided into success group (healed or healing with wound reduction), stagnate group, and failure group (amputation or infection, need in-hospital medical service) in accordance with the treatment response of wounds. χ Test, Fisher exact test, and 1-way analysis of variance were used for variables in 3-group comparison, whereas Student t test was applied in 2-group comparison. The predictive factors with P value less than 0.1 were further investigated using the model of univariate logistic regression. RESULTS: With 3-group stratification according to treatment response-failure (n = 8), stagnate (n = 22), and success (n = 70)-the occurrence rate of retinopathy was higher in the treatment stagnate group (42.1%) than in the treatment failure (14.3%) and success groups (12.5%; P = 0.019); the rate of previous percutaneous transluminal angioplasty (PTA) history was higher in the treatment failure group (25%) than in the treatment stagnate (4.8%) and success groups (1.5%; P = 0.020). With 2-group stratification-failure (n = 8) versus nonfailure (n = 92), and success (n = 70) versus nonsuccess (n = 30)-PTA history was strongly associated with treatment failure (odds ratio [OR], 14.33; 95% confidence interval [CI], 1.71-120.32; P = 0.014), whereas retinopathy (OR, 0.21; 95% CI, 0.07-0.65; P = 0.006) was the major negative predictor for treatment success. Previous debridement met borderline significance to predict treatment nonsuccess (OR, 0.09; 95% CI, 0.01-1.01; P = 0.051). Sex, age, associated history, dyslipidemia, hypertension, coronary artery disease, cerebrovascular accident, chronic kidney disease, and end-stage renal disease and wound condition had no statistical significance. CONCLUSIONS: Previous PTA and retinopathy, which indicated preexisting severe vasculopathy, are univariate predictive factors for treatment failure and nonsuccess, respectively, in patients with King classification III DFU. With the subdivision of King classification III DFU, medical history taking and fundus examination are acceptable methods for risk screening at an outpatient clinic.

Co-housing reverses memory decline by epigenetic regulation of brain-derived neurotrophic factor expression in an animal model of Alzheimer's disease.

Co-housing with a company exerts profound effects on memory decline in animal model of Alzheimer's disease (AD). Recently, we found that APP/PS1 mice of 9-month-old improved their memories after co-housing with wide-type mice for 3months by increasing hippocampal brain-derived neurotrophic factor (BDNF) expression. However, the mechanism of how co-housing could induce BDNF expression remains elusive. Here we examined epigenetic changes in the mouse hippocampus that accompanied the co-housing-induced memory improvement. We found that the level of histone deacetylase 2 (HDAC2), but not that of HDAC1, was significantly lower in the memory improved mice than in the control and memory un-improved APP/PS1 mice after co-housing. Knockdown of Hdac2 resulted in a higher freezing response after co-housing. Conversely, over-expression of HDAC2 blocked co-housing-induced memory improvement. The level of Bdnf exon IV mRNA increased significantly after knockdown of Hdac2. ChIP assay revealed a decreased occupancy of HDAC2 in the promoter region of Bdnf exon IV of memory improved mice but not memory un-improved and control APP/PS1 mice. Consistently, the acetylation of histone 3 on Lys 9 (H3K9) and histone 4 on Lys12 (H4K12) increased significantly in the promoter region of Bdnf exon IV. These results suggest HDAC2 expression is reduced after co-housing resulting in a decreased occupancy of HDAC2 and increased histone H3K9 and H4K12 acetylation in the promoter region of Bdnf exon IV, leading to increased BDNF expression in the hippocampus that improves memory.

Synergistic inhibition of tumor growth by combination treatment with drugs against different subpopulations of glioblastoma cells.

BACKGROUND: Glioma stem cells (GSCs) contribute to tumor recurrence and drug resistance. This study characterizes the tumorigenesis of CD133+ cells and their sensitivity to pharmacological inhibition. METHODS: GSCs from human U87 and rat C6 glioblastoma cell lines were isolated via magnetic cell sorting using CD133 as a cancer stem cell marker. Cell proliferation was determined using the WST-1 assay. An intracranial mouse model and bioluminescence imaging were used to assess the effects of drugs on tumor growth in vivo. RESULTS: CD133+ cells expressed stem cell markers and exhibited self-renewal and enhanced tumor formation. Minocycline (Mino) was more effective in reducing the survival rate of CD133+ cells, whereas CD133- cells were more sensitive to inhibition by the signal transducer and activator of transcription 3 (STAT3) inhibitor. Inhibition of STAT3 decreased the expression of CD133+ stem cell markers. The combination of Mino and STAT3 inhibitor synergistically reduced the cell viability of glioma cells. Furthermore, this combination synergistically suppressed tumor growth in nude mice. CONCLUSION: The results suggest that concurrent targeting of different subpopulations of glioblastoma cells may be an effective therapeutic strategy for patients with malignant glioma.

Identification and characterization of the microRNA transcriptome of a moth orchid Phalaenopsis aphrodite.

Orchids display unique phenotypes, functional characteristics and ecological adaptations that are not found in model plants. In this study, we aimed to characterize the microRNA (miRNA) transcriptome and identify species- and tissue-specific miRNAs in Phalaenopsis aphrodite. After data filtering and cleanup, a total of 59,387,374 reads, representing 1,649,996 unique reads, were obtained from four P. aphrodite small RNA libraries. A systematic bioinformatics analysis pipeline was developed that can be used for miRNA and precursor mining, and target gene prediction in non-model plants. A total of 3,251 unique reads for 181 known plant miRNAs (belonging to 88 miRNA families), 23 new miRNAs and 91 precursors were identified. All the miRNA star sequences (miRNA*), the complementary strands of miRNA that from miRNA/miRNA* duplexes, of the predicted new miRNAs were detected in our small RNA libraries, providing additional evidence for their existence as new miRNAs in P. aphrodite. Furthermore, 240 potential miRNA-targets that appear to be involved in many different biological activities and molecular functions, especially transcription factors, were identified, suggesting that miRNAs can impact multiple processes in P. aphrodite. We also verified the cleavage sites for six targets using RNA ligase-mediated rapid amplification of 5' ends assay. The results provide valuable information about the composition, expression and function of miRNA in P. aphrodite, and will aid functional genomics studies of orchids.

The beneficial effects of leptin on REM sleep deprivation-induced cognitive deficits in mice.

Leptin, a 167 amino acid peptide, is synthesized predominantly in the adipose tissues and plays a key role in the regulation of food intake and body weight. Recent studies indicate that leptin receptor is expressed with high levels in many brain regions that may regulate synaptic plasticity. Here we show that deprivation of rapid eye movement (REMD) sleep resulted in impairment of both cue and contextual fear memory. In parallel, surface expression of GluR1 was reduced in the amygdala. Intraperitoneal injection of leptin to the REMD mice rescued memory impairment and reversed surface GluR1 reduction. Using whole-cell recording to evaluate the synaptic function of the thalamus-lateral amygdala (LA) pathway, we found a decrease in frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) concomitant with reduced AMPA/NMDA ratios in the REMD mice. By contrast, paired-pulse facilitation (PPF) was increased. The effects of REMD on mEPSCs and AMPA/NMDA ratio could be reversed by leptin treatment, whereas on PPR it could not. Phosphatase and tensin homolog (PTEN), a dual protein/lipid phosphatase, down-regulates the effect of the PI-3 kinase pathway. Fear conditioning increased whereas REMD led to a decrease in the phosphorylated states of PTEN, Akt, and glycogen synthase kinase-3ß (GSK3ß), and the effects of REMD were reversed by leptin. These results suggest that both pre- and postsynaptic functions of the thalamus-LA pathway were altered by fear conditioning and REMD in opposite directions. Leptin treatment reversed REMD-induced memory deficits primarily by a postsynaptic action by restoring surface expression of GluR1 without affecting PPR.

Giant Interpectoral Lipoma Causing Venous Thoracic Outlet Syndrome: A Rare Case Presentation.

Lipomas are the most prevalent type of benign soft tissue tumors, primarily composed of adipocytes, and typically remain asymptomatic unless they reach a significant size. Although giant lipomas are infrequent, their occurrence on the chest wall, particularly in the interpectoral region, is exceedingly rare. We present a unique case of a 48-year-old man with a massive interpectoral lipoma measuring 19.4 × 12.9 × 9.4 cm, which resulted in venous thoracic outlet syndrome by compressing the subclavian vein. This case highlights the clinical challenges in diagnosing deep-seated chest wall lipomas and underscores the necessity of considering thoracic outlet syndrome as a potential complication, even in the absence of direct neural or arterial compression. The presentation of thoracic outlet syndrome can vary, and a comprehensive evaluation is imperative for accurate diagnosis and management.

Temporomandibular joint degenerative changes following mandibular fracture: a computed tomography-based study on the role of condylar involvement.

OBJECTIVES: This study assessed the incidence of postfracture radiological temporomandibular joint (TMJ) degeneration in patients with different types of mandibular fractures, focusing on the impact of condylar fractures. METHODS: This retrospective review included patients diagnosed as having mandibular fractures from 2016 to 2020 who had undergone initial computed tomography (CT) and a follow-up CT scan at least 1-month postfracture. Patient demographics, fracture details, treatment methods, and radiological signs of TMJ degeneration on CT were analyzed to identify risk factors for postfracture TMJ degeneration, with a focus on condylar head fracture and non-head (condylar neck or base) fractures. RESULTS: The study included 85 patients (mean age: 38.95 ± 17.64 years). The per-patient analysis indicated that the incidence of new radiologic TMJ degeneration on CT was significantly the highest (p < 0.001) in patients with condylar head fractures (90.91%), followed by those with non-head condylar fractures (57.14%), and those without condylar involvement (24.49%). The per-joint analysis indicated nearly inevitable degeneration (93.94%) in 33 TMJs with ipsilateral condylar head fractures. For the remaining 137 TMJs, multivariate logistic regression revealed that other patterns (ipsilateral non-head, contralateral, or both) of condylar fractures (odds ratio (OR) = 3.811, p = 0.007) and the need for open reduction and internal fixation (OR = 5.804, p = 0.005) significantly increased the risk of TMJ degeneration. CONCLUSIONS: Ipsilateral non-head condylar fractures and contralateral condylar fractures are associated with a high risk of postfracture TMJ degeneration. Indirect trauma plays a vital role in postfracture TMJ degeneration.

Enhancing precision in lung tumor ablation through innovations in CT-guided technique and angle control.

BACKGROUND: This retrospective study aimed to evaluate the precision and safety outcomes of image-guided lung percutaneous thermal ablation (LPTA) methods, focusing on radiofrequency ablation (RFA) and microwave ablation (MWA). The study utilized an innovative angle reference guide to facilitate these techniques in the treatment of lung tumors. METHODS: This study included individuals undergoing LPTA with the assistance of laser angle guide assembly (LAGA) at our hospital between April 2011 and March 2021. We analyzed patient demographics, tumor characteristics, procedure details, and complications. Logistic regressions were employed to assess risk factors associated with complications. RESULTS: A total of 202 patients underwent ablation for 375 lung tumors across 275 sessions involving 495 ablations. Most procedures used RFA, especially in the right upper lobe, and the majority of ablations were performed in the prone position (49.7%). Target lesions were at a median depth of 39.3 mm from the pleura surface, and remarkably, 91.9% required only a single puncture. Complications occurred in 31.0% of ablations, with pneumothorax being the most prevalent (18.3%), followed by pain (12.5%), sweating (6.5%), fever (5.0%), cough (4.8%), hemothorax (1.6%), hemoptysis (1.2%), pleural effusion (2.0%), skin burn (0.6%), and air emboli (0.2%). The median procedure time was 21 min. Notably, smoking/chronic obstructive pulmonary disease emerged as a significant risk factor for complications. CONCLUSION: The LAGA-assisted LPTA enhanced safety by improving accuracy and reducing risks. Overall, this investigation contributes to the ongoing efforts to refine and improve the clinical application of these thermal ablation techniques in the treatment of lung tumors.

Orchidstra: an integrated orchid functional genomics database.

A specialized orchid database, named Orchidstra (URL: http://orchidstra.abrc.sinica.edu.tw), has been constructed to collect, annotate and share genomic information for orchid functional genomics studies. The Orchidaceae is a large family of Angiosperms that exhibits extraordinary biodiversity in terms of both the number of species and their distribution worldwide. Orchids exhibit many unique biological features; however, investigation of these traits is currently constrained due to the limited availability of genomic information. Transcriptome information for five orchid species and one commercial hybrid has been included in the Orchidstra database. Altogether, these comprise >380,000 non-redundant orchid transcript sequences, of which >110,000 are protein-coding genes. Sequences from the transcriptome shotgun assembly (TSA) were obtained either from output reads from next-generation sequencing technologies assembled into contigs, or from conventional cDNA library approaches. An annotation pipeline using Gene Ontology, KEGG and Pfam was built to assign gene descriptions and functional annotation to protein-coding genes. Deep sequencing of small RNA was also performed for Phalaenopsis aphrodite to search for microRNAs (miRNAs), extending the information archived for this species to miRNA annotation, precursors and putative target genes. The P. aphrodite transcriptome information was further used to design probes for an oligonucleotide microarray, and expression profiling analysis was carried out. The intensities of hybridized probes derived from microarray assays of various tissues were incorporated into the database as part of the functional evidence. In the future, the content of the Orchidstra database will be expanded with transcriptome data and genomic information from more orchid species.

[Effects of testosterone on insulin sensitivity in liver cells and related molecular mechanisms].

OBJECTIVE: To explore the regulation of insulin sensitivity in liver cells by androgen signaling. METHODS: Eleven adult female C57BL/6 mice were injected daily with testosterone (group T) for 24 weeks. And 10 control mice received sesame oil only (group Con). HepG2 liver cells were initially pretreated with different doses of testosterone (10(-9)-10(-5) mol/L ) for 0-36 h or with 10(-7) mol/L testosterone for 0-96 h followed by a stimulation of 100 nmol/L insulin for 15 min. Later HepG2 cells were pretreated with 10(-7) mol/L testosterone for 36 h followed by a stimulation of 100 nmol/L insulin for 15 min and then a restimulation of 100 nmol/L insulin for 15 min at 4 h and 6 h interval respectively. Phosphorylation and protein expression of Akt and GSK3ß in C57BL/6 mice liver tissues and HepG2 cells were analyzed by Western blot. RESULTS: The 24-week treatment of testosterone decreased the phosphorylation of Akt and GSK3ß in C57BL/6 adipose and liver tissues (43.1% ± 3.2% vs 77.1% ± 6.7%, 14.7% ± 6.7% vs 82.3% ± 2.0% respectively, P < 0.05). Pretreatment with 10(-8)-10(-6) mol/L testosterone within 36 h obviously increased the phosphorylation of Akt and GSK3ß (P < 0.05). However pretreatment with 10(-5) mol/L within 36 h or with 10(-7) mol/L for 96 h had no effect on the phosphorylation of Akt and GSK3ß compared with control group (P > 0.05). Pretreatment with 10(-7) mol/L testosterone for 36 h followed by insulin stimulation and restimulation after 6 h interval obviously decreased the phosphorylation of Akt and GSK3ß (P < 0.05). CONCLUSION: Androgen signaling may contribute to insulin resistance in liver cells.

Velopharyngeal function change after two-jaw orthognathic surgery in patients with cleft: A study on 162 consecutive cases.

BACKGROUND: Orthognathic surgery (OGS) is a common intervention used to correct midfacial hypoplasia in patients with cleft. Previous studies have reported that LeFort I maxillary advancement may impact velopharyngeal function, but similar investigations focusing on two-jaw OGS have not been conducted. METHODS: A total of 162 consecutive patients with cleft lip and palate who underwent two-jaw OGS between 2015 and 2020 were enrolled. Clinical data were collected, and preoperative and postoperative skeletal measurements were obtained from cephalometric images. Velopharyngeal function was evaluated using perceptual analysis and nasopharyngoscopy. A logistic regression model was employed for the risk factors associated with changes in velopharyngeal function. RESULTS: After two-jaw OGS, 82.1% of patients showed no change in velopharyngeal function, while 3.7% experienced improvement and 14.2% exhibited worsening of function. In addition, the changes in velopharyngeal function were statistically significant comparing to the pre-OGS velopharyngeal status. A multivariable logistic regression revealed that the amount of maxillary advancement independently predicted the deterioration of post-OGS velopharyngeal function (odds ratio = 1.74, 95% confidence interval (CI) = 1.20-2.52, p = 0.004). The receiver operating characteristic curve based on maxillary advancement demonstrated good discrimination, with an area under the curve of 0.727 (95% CI = 0.62-0.83, p = 0.001). The Youden index was 4.27 mm. CONCLUSION: Despite the risk of velopharyngeal function deterioration in patients with cleft palate undergoing OGS, some individuals have experienced improved function following two-jaw OGS. The extent of maxillary advancement has a negative impact on the velopharyngeal function.

A Simple Scoring Model for Evaluation of Concomitant Vascular Injuries in Patients with Lower Extremity Open Fractures.

BACKGROUND: Timely diagnosis and management of concomitant vascular injuries is usually needed for the management of lower extremity open fractures. In the current study, a prediction model and simplified scoring system of vascular injuries were developed for the primary evaluation of patients with lower extremity open fractures. METHODS: Patients with lower extremity open fractures were retrospectively reviewed from 2017 to 2020. Multivariate logistic regression analysis was used to evaluate independent risk factors for concomitant vascular injuries in these patients using data collected from 2017 through 2019 and a prediction scoring model was created accordingly. Model performance was validated with data from 2020. RESULTS: In total, 949 patients with lower extremity open fractures (development cohort, 705 patients, 2017 through 2019; validation cohort, 244 patients, 2020) were enrolled. Concomitant vascular injuries occurred in 44 patients in the development cohort (6.2%). Three clinical variables were identified for a prediction scoring model with weighted points, including hard or soft vascular signs (3 points), segmental fractures (2 points), and degloving soft-tissue injury (1 point). The model showed good discrimination (area under the receiver operating characteristic curve, 0.928), calibration (Hosmer-Lemeshow test, P = 0.661), and precision (Brier score, 0.041). Subsequent management regarding different aspects (observation only, further imaging study, or direct surgical exploration) can thus be decided. The model also demonstrated good discrimination (area under the receiver operating characteristic curve, 0.949), good calibration (Hosmer-Lemeshow test, P = 0.174), and good precision (Brier score, 0.042) in the validation cohort. CONCLUSION: This model may guide the subsequent management of vascular injuries associated with lower extremity open fractures. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Modulation of methamphetamine memory reconsolidation by neural projection from basolateral amygdala to nucleus accumbens.

Drug-associated conditioned cues promote subjects to recall drug reward memory, resulting in drug-seeking and reinstatement. A consolidated memory becomes unstable after recall, such that the amnestic agent can disrupt the memory during the reconsolidation stage, which implicates a potential therapeutic strategy for weakening maladaptive memories. The basolateral amygdala (BLA) involves the association of conditioned cues with reward and aversive valences and projects the information to the nucleus accumbens (NAc) that mediates reward-seeking. However, whether the BLA-NAc projection plays a role in drug-associated memory reactivation and reconsolidation is unknown. We used methamphetamine (MeAM) conditioned place preference (CPP) to investigate the role of BLA-NAc neural projection in the memory reconsolidation. Two weeks before CPP training, we infused adeno-associated virus (AAV) carrying the designer receptor exclusively activated by designer drugs (DREADD) or control constructs. We infused clozapine-N-oxide (CNO) after the recall test to manipulate the neural activity of BLA-NAc projections in mice. We found that after recall, DREADD-mediated inhibition of BLA neurons projecting to the NAc core blunted consolidated MeAM-associated memory. Inhibition of BLA glutamatergic nerve terminals in the NAc core 1 h after recall disrupted consolidated MeAM-associated memory. However, inhibiting this pathway after the time window of reconsolidation failed to affect memory. Furthermore, under the condition without memory retrieval, DREADD-mediated activation of BLA-NAc core projection was required for amnesic agents to disrupt consolidated MeAM-associated memory. Our findings provide evidence that the BLA-NAc pathway activity is involved in the post-retrieval processing of MeAM-associated memory in CPP.

Pretreatment with Lovastatin Improves Depression-Like Behavior After Traumatic Brain Injury Through Activation of the AMPK Pathway.

BACKGROUND: The beneficial effect of pretreatment with statins on traumatic brain injury (TBI)-induced depression and anxiety and its mechanism of action remain unclear. In this study, we combined epidemiological and experimental animal data to clarify this issue. METHODS: We used the Taiwan National Health Insurance database to identify patients who were diagnosed with TBI from 2000 to 2013 and compared patients with and without statin treatment matched by age, sex, and underlying comorbidities in a 1:1 ratio. The risk of developing depression and/or anxiety was compared between patients with and without a statin using Cox proportional hazards regression. We also used a rat model to assess the effect of lovastatin pretreatment on neurobehavioral and neuropathological changes following TBI. RESULTS: The risk of developing depression was lower in the 41,803 patients in the statin cohort than nonstatin cohort (adjusted hazard ratio, 0.91 [95% confidence interval, 0.83-0.99]). In animal models, the lovastatin group had significantly reduced infarct volume, decreased immobility time and latency to eat, a reduced number of Fluoro- Jade-positive cells and levels of glial fibrillary acidic protein and tumor necrosis factor-alpha, and increased adenosine monophosphate -activated protein kinase (AMPK) and its upstream kinase liver kinase B1 in the hippocampal dentate gyrus. These effects were blocked in AMPK inhibitor-pretreated TBI rats. CONCLUSIONS: Our epidemiological data showed that a decreased risk of depression was associated with statin pretreatment, which was supported by an animal study. The underlying mechanism for this appears to involve AMPK activation in the statin pretreatment-induced alleviation of TBI.