Liver involvement with Langerhans cell histiocytosis in adults.

BACKGROUND AND AIMS: Liver involvement portends poor prognosis in adults. We aimed to characterize the clinical features, liver function tests, radiologic findings, molecular profiles, therapeutic approaches and outcomes of adults patients with Langerhans cell histiocytosis (LCH) with liver involvement. METHODS: We conducted a retrospective analysis of all adults with LCH (≥ 18 years) seen at Peking Union Medical College Hospital (Beijing, China) between January 2001 and December 2022. RESULTS: Among the 445 newly diagnosed adults with LCH, 90 patients had liver involvement at diagnosis and 22 patients at relapse. The median age was 32 years (range, 18-66 years). Of 112 evaluable patients, 108 had full liver function testing, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), and total bilirubin and albumin. Elevated ALP was seen in 63.0% and GGT in 86.1%; 14.8% had elevated bilirubin. Next-generation sequencing of 54 patients revealed frequent BRAFN486_P490 (29.6%), BRAFV600E (18.5%), and MAP2K1 (14.8%). OUTCOMES: After a median 40 months' follow-up (range 1-168 months), 3-year progression-free survival (PFS) and overall survival were 49.7% and 86.6% respectively. In multivariable analyses, ≥3 abnormal liver function tests (HR 3.384, 95% CI 1.550-7.388, P = .002) associated with inferior PFS; immunomodulatory drug therapy (HR 0.073, 95% CI, 0.010-0.541, P = .010) correlated with superior PFS versus chemotherapy. CONCLUSIONS: In summary, elevated GGT and ALP were common in adults with LCH liver involvement. Greater than equal to 3 abnormal liver function tests predicted poor outcomes. Immunomodulatory drug therapy was associated with favorable progression-free survival compared to chemotherapy.

Artificial Intelligence and Virtual Reality in Headache Disorder Diagnosis, Classification, and Management.

PURPOSE OF REVIEW: This review provides an overview of the current and future role of artificial intelligence (AI) and virtual reality (VR) in addressing the complexities inherent to the diagnosis, classification, and management of headache disorders. RECENT FINDINGS: Through machine learning and natural language processing approaches, AI offers unprecedented opportunities to identify patterns within complex and voluminous datasets, including brain imaging data. This technology has demonstrated promise in optimizing diagnostic approaches to headache disorders and automating their classification, an attribute particularly beneficial for non-specialist providers. Furthermore, AI can enhance headache disorder management by enabling the forecasting of acute events of interest, such as migraine headaches or medication overuse, and by guiding treatment selection based on insights from predictive modeling. Additionally, AI may facilitate the streamlining of treatment efficacy monitoring and enable the automation of real-time treatment parameter adjustments. VR technology, on the other hand, offers controllable and immersive experiences, thus providing a unique avenue for the investigation of the sensory-perceptual symptomatology associated with certain headache disorders. Moreover, recent studies suggest that VR, combined with biofeedback, may serve as a viable adjunct to conventional treatment. Addressing challenges to the widespread adoption of AI and VR in headache medicine, including reimbursement policies and data privacy concerns, mandates collaborative efforts from stakeholders to enable the equitable, safe, and effective utilization of these technologies in advancing headache disorder care. This review highlights the potential of AI and VR to support precise diagnostics, automate classification, and enhance management strategies for headache disorders.

Telehealth and Virtual Reality Technologies in Chronic Pain Management: A Narrative Review.

PURPOSE OF REVIEW: This review provides medical practitioners with an overview of the present and emergent roles of telehealth and associated virtual reality (VR) applications in chronic pain (CP) management, particularly in the post-COVID-19 healthcare landscape. RECENT FINDINGS: Accumulated evidence points to the efficacy of now well-established telehealth modalities, such as videoconferencing, short messaging service (SMS), and mobile health (mHealth) applications in complementing remote CP care. More recently, and although still in early phases of clinical implementation, a wide range of VR-based interventions have demonstrated potential for improving the asynchronous remote management of CP. Additionally, VR-associated technologies at the leading edge of science and engineering, such as VR-assisted biofeedback, haptic technology, high-definition three-dimensional (HD3D) conferencing, VR-enabled interactions in a Metaverse, and the use of wearable monitoring devices, herald a new era for remote, synchronous patient-physician interactions. These advancements hold the potential to facilitate remote physical examinations, personalized remote care, and innovative interventions such as ultra-realistic biofeedback. Despite the promise of VR-associated technologies, several limitations remain, including the paucity of robust long-term effectiveness data, heterogeneity of reported pain-related outcomes, challenges with scalability and insurance coverage, and demographic-specific barriers to patient acceptability. Future research efforts should be directed toward mitigating these limitations to facilitate the integration of telehealth-associated VR into the conventional management of CP. Despite ongoing barriers to widespread adoption, recent evidence suggests that VR-based interventions hold an increasing potential to complement and enhance the remote delivery of CP care.

Cancer stem cell-derived CHI3L1 activates the MAF/CTLA4 signaling pathway to promote immune escape in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) development may be associated with tumor immune escape. This study explores whether the CHI3L1/MAF/CTLA4/S100A4 axis affects immune escape in TNBC through interplay with triple-negative breast cancer stem cells (TN-BCSCs). OBJECTIVE: The aim of this study is to utilize single-cell transcriptome sequencing (scRNA-seq) to uncover the molecular mechanisms by which the CHI3L1/MAF/CTLA4 signaling pathway may mediate immune evasion in triple-negative breast cancer through the interaction between tumor stem cells (CSCs) and immune cells. METHODS: Cell subsets in TNBC tissues were obtained through scRNA-seq, followed by screening differentially expressed genes in TN-BCSCs and B.C.s (CD44+ and CD24-) and predicting the transcription factor regulated by CHI3L1. Effect of CHI3L1 on the stemness phenotype of TNBC cells investigated. Effects of BCSCs-231-derived CHI3L1 on CTLA4 expression in T cells were explored after co-culture of BCSCs-231 cells obtained from microsphere culture of TN-BCSCs with T cells. BCSCs-231-treated T cells were co-cultured with CD8+ T cells to explore the resultant effect on T cell cytotoxicity. An orthotopic B.C. transplanted tumor model in mice with humanized immune systems was constructed, in which the Role of CHI3L1/MAF/CTLA4 in the immune escape of TNBC was explored. RESULTS: Eight cell subsets were found in the TNBC tissues, and the existence of TN-BCSCs was observed in the epithelial cell subset. CHI3L1 was related to the stemness phenotype of TNBC cells. TN-BCSC-derived CHI3L1 increased CTLA4 expression in T cells through MAF, inhibiting CD8+ T cell cytotoxicity and inducing immunosuppression. Furthermore, the CTLA4+ T cells might secrete S100A4 to promote the stemness phenotype of TNBC cells. CONCLUSIONS: TN-BCSC-derived CHI3L1 upregulates CTLA4 expression in T cells through MAF, suppressing the function of CD8+ T cells, which promotes the immune escape of TNBC.

Motion guidance lines for robust data consistency-based retrospective motion correction in 2D and 3D MRI.

PURPOSE: To develop a robust retrospective motion-correction technique based on repeating k-space guidance lines for improving motion correction in Cartesian 2D and 3D brain MRI. METHODS: The motion guidance lines are inserted into the standard sequence orderings for 2D turbo spin echo and 3D MPRAGE to inform a data consistency-based motion estimation and reconstruction, which can be guided by a low-resolution scout. The extremely limited number of required guidance lines are repeated during each echo train and discarded in the final image reconstruction. Thus, integration within a standard k-space acquisition ordering ensures the expected image quality/contrast and motion sensitivity of that sequence. RESULTS: Through simulation and in vivo 2D multislice and 3D motion experiments, we demonstrate that respectively 2 or 4 optimized motion guidance lines per shot enables accurate motion estimation and correction. Clinically acceptable reconstruction times are achieved through fully separable on-the-fly motion optimizations (˜1 s/shot) using standard scanner GPU hardware. CONCLUSION: The addition of guidance lines to scout accelerated motion estimation facilitates robust retrospective motion correction that can be effectively introduced without perturbing standard clinical protocols and workflows.

Optimization of magnetization transfer contrast for EPI FLAIR brain imaging.

PURPOSE: To evaluate the impact of magnetization transfer (MT) on brain tissue contrast in turbo-spin-echo (TSE) and EPI fluid-attenuated inversion recovery (FLAIR) images, and to optimize an MT-prepared EPI FLAIR pulse sequence to match the tissue contrast of a clinical reference TSE FLAIR protocol. METHODS: Five healthy volunteers underwent 3T brain MRI, including single slice TSE FLAIR, multi-slice TSE FLAIR, EPI FLAIR without MT-preparation, and MT-prepared EPI FLAIR with variations of the MT-preparation parameters, including number of preparation pulses, pulse amplitude, and resonance offset. Automated co-registration and gray matter (GM) versus white matter (WM) segmentation was performed using a T1-MPRAGE acquisition, and the GM versus WM signal intensity ratio (contrast ratio) was calculated for each FLAIR acquisition. RESULTS: Without MT preparation, EPI FLAIR showed poor tissue contrast (contrast ratio = 0.98), as did single slice TSE FLAIR. Multi-slice TSE FLAIR provided high tissue contrast (contrast ratio = 1.14). MT-prepared EPI FLAIR closely approximated the contrast of the multi-slice TSE FLAIR images for two combinations of the MT-preparation parameters (contrast ratio = 1.14). Optimized MT-prepared EPI FLAIR provided a 50% reduction in scan time compared to the reference TSE FLAIR acquisition. CONCLUSION: Optimized MT-prepared EPI FLAIR provides comparable brain tissue contrast to the multi-slice TSE FLAIR images used in clinical practice.

Inference of population structure and admixture proportion from Y chromosomal data of Chinese population.

In the past two decades, Y chromosome data has been generated for human population genetic studies. These Y chromosome datasets were produced with various testing methods and markers, thus difficult to combine them for a comprehensive analysis. In this study, we combine four human Y chromosomal datasets of Han, Tibetan, Hui, and Li ethnic groups. The dataset contains 27 microsatellites and 137 single nucleotide polymorphisms these populations share in common. We assembled a single dataset containing 2439 individuals from 25 nationwide populations in China. A systematic analysis of genetic distance and clustering was performed. To determine the gene flow of the studied population with worldwide populations, we modeled the ancestry informative markers. The reference panel was regarded as a mixture of South Asian (SAS), East Asian (EAS), European (EUR), African (AFR), and American (AMR) populations from 1000 Genomes data of Y chromosome using nonlinear data-fitting. We then calculated the admixture proportion of these four studied populations with 26 worldwide populations. The results showed that the Han and Hui have great genetic affinity, and Hui is the most admixed ethnic group, with 61.53% EAS, 34.65% SAS, 1.91% AFR, 1.56% AMR, and 0.04% EUR ancestry component (the AMR is highly admixed and thus should be ignored). All the other three ethnic groups contained more than 97% EAS ancestry component. The Li is the least admixed population in this study. The combined dataset in this study is the largest of this kind reported to date and proposes reference population data for use in future paternal genetic studies and forensic genealogical identification.

Exploitation of a novel slowly mutating Y-STRs set and evaluation of slowly mutating Y-STRs plus Y-SNPs typing strategy in forensic genetics and evolutionary research.

The Y-chromosome short tandem repeats (Y-STRs) loci with different mutation rates existing in the Y chromosome non-recombination region (NRY) allow to be applied in human forensics, genealogical researches, historical investigations and evolutionary studies. Currently, there is a high demand for pedigree search to narrow the scope of crime investigations. However, the commonly used Y-STRs kits generally contain Y-STRs with high mutation rates that could cause individuals from the same pedigree to display different haplotypes. Herein, we put forward a new strategy of Slowly Mutating (SM) Y-STRs plus Y-SNPs typing, which could not only improve the resolution and accuracy of pedigree search, but also be applicable to evolutionary research. First, we developed a nine SM Y-STRs assay by evaluating their mutation rates in 210 pedigrees. Then the gene diversity and efficiency of the SM Y-STRs and 172 Y-SNPs sets were investigated by 2304 unrelated males from 24 populations. Furthermore, network and time estimation analyses were performed to evaluate the new strategy's capability to reconstruct phylogenetic tree and reliability to infer the time to the most recent common ancestor (TMRCA). The nine SM Y-STRs assay even had a higher resolution and a comparable capacity of revealing population genetic differentiation compared to 172 Y-SNPs system. This new strategy could optimize the phylogenetic tree generated by commonly used Y-STR panels and obtain a quite consistent time estimations with the published dating.

Comparison of Chest CT Findings of COVID-19, Influenza, and Organizing Pneumonia: A Multireader Study.

BACKGROUND. Previous studies compared CT findings of COVID-19 pneumonia with those of other infections; however, to our knowledge, no studies to date have included noninfectious organizing pneumonia (OP) for comparison. OBJECTIVE. The objectives of this study were to compare chest CT features of COVID-19, influenza, and OP using a multireader design and to assess the performance of radiologists in distinguishing between these conditions. METHODS. This retrospective study included 150 chest CT examinations in 150 patients (mean [± SD] age, 58 ± 16 years) with a diagnosis of COVID-19, influenza, or non-infectious OP (50 randomly selected abnormal CT examinations per diagnosis). Six thoracic radiologists independently assessed CT examinations for 14 individual CT findings and for Radiological Society of North America (RSNA) COVID-19 category and recorded a favored diagnosis. The CT characteristics of the three diagnoses were compared using random-effects models; the diagnostic performance of the readers was assessed. RESULTS. COVID-19 pneumonia was significantly different (p < .05) from influenza pneumonia for seven of 14 chest CT findings, although it was different (p < .05) from OP for four of 14 findings (central or diffuse distribution was seen in 10% and 7% of COVID-19 cases, respectively, vs 20% and 21% of OP cases, respectively; unilateral distribution was seen in 1% of COVID-19 cases vs 7% of OP cases; non-tree-in-bud nodules was seen in 32% of COVID-19 cases vs 53% of OP cases; tree-in-bud nodules were seen in 6% of COVID-19 cases vs 14% of OP cases). A total of 70% of cases of COVID-19, 33% of influenza cases, and 47% of OP cases had typical findings according to RSNA COVID-19 category assessment (p < .001). The mean percentage of correct favored diagnoses compared with actual diagnoses was 44% for COVID-19, 29% for influenza, and 39% for OP. The mean diagnostic accuracy of favored diagnoses was 70% for COVID-19 pneumonia and 68% for both influenza and OP. CONCLUSION. CT findings of COVID-19 substantially overlap with those of influenza and, to a greater extent, those of OP. The diagnostic accuracy of the radiologists was low in a study sample that contained equal proportions of these three types of pneumonia. CLINICAL IMPACT. Recognized challenges in diagnosing COVID-19 by CT are furthered by the strong overlap observed between the appearances of COVID-19 and OP on CT. This challenge may be particularly evident in clinical settings in which there are substantial proportions of patients with potential causes of OP such as ongoing cancer therapy or autoimmune conditions.

Long-term neuroimaging follow-up of COVID-19-related leukoencephalopathy.

More than a year after the start of the COVID-19 pandemic, long-term neurological manifestations of COVID-19 are increasingly being reported. The long-term sequelae of COVID-19-related leukoencephalopathy, however, remain unclear. Here, we present long-term neuroimaging follow-up in two cases of COVID-19-related leukoencephalopathy. The two cases demonstrate the utility of brain MRI for evaluating neurologic symptoms in critically ill patients with COVID-19, for diagnosis of underlying neural injury and prognostication of future recovery. The presence of leukoencephalopathy may result in chronic neurologic manifestations and may represent a poor prognosticator of neurologic recovery. The presence of leukoencephalomalacia on follow-up neuroimaging is potentially an indicator of irreversible white matter damage, which may be associated with more severe chronic deficits.

Right Ventricular Strain Is Common in Intubated COVID-19 Patients and Does Not Reflect Severity of Respiratory Illness.

BACKGROUND: Right ventricular (RV) dysfunction is common and associated with worse outcomes in patients with coronavirus disease 2019 (COVID-19). In non-COVID-19 acute respiratory distress syndrome, RV dysfunction develops due to pulmonary hypoxic vasoconstriction, inflammation, and alveolar overdistension or atelectasis. Although similar pathogenic mechanisms may induce RV dysfunction in COVID-19, other COVID-19-specific pathology, such as pulmonary endothelialitis, thrombosis, or myocarditis, may also affect RV function. We quantified RV dysfunction by echocardiographic strain analysis and investigated its correlation with disease severity, ventilatory parameters, biomarkers, and imaging findings in critically ill COVID-19 patients. METHODS: We determined RV free wall longitudinal strain (FWLS) in 32 patients receiving mechanical ventilation for COVID-19-associated respiratory failure. Demographics, comorbid conditions, ventilatory parameters, medications, and laboratory findings were extracted from the medical record. Chest imaging was assessed to determine the severity of lung disease and the presence of pulmonary embolism. RESULTS: Abnormal FWLS was present in 66% of mechanically ventilated COVID-19 patients and was associated with higher lung compliance (39.6 vs 29.4 mL/cmH2O, P = 0.016), lower airway plateau pressures (21 vs 24 cmH2O, P = 0.043), lower tidal volume ventilation (5.74 vs 6.17 cc/kg, P = 0.031), and reduced left ventricular function. FWLS correlated negatively with age (r = -0.414, P = 0.018) and with serum troponin (r = 0.402, P = 0.034). Patients with abnormal RV strain did not exhibit decreased oxygenation or increased disease severity based on inflammatory markers, vasopressor requirements, or chest imaging findings. CONCLUSIONS: RV dysfunction is common among critically ill COVID-19 patients and is not related to abnormal lung mechanics or ventilatory pressures. Instead, patients with abnormal FWLS had more favorable lung compliance. RV dysfunction may be secondary to diffuse intravascular micro- and macro-thrombosis or direct myocardial damage. TRIAL REGISTRATION: National Institutes of Health #NCT04306393. Registered 10 March 2020, https://clinicaltrials.gov/ct2/show/NCT04306393.

Quiescent hepatic stellate cells induce toxicity and sensitivity to doxorubicin in cancer cells through a caspase-independent cell death pathway: Central role of apoptosis-inducing factor.

Hepatocellular carcinoma (HCC) is a major health problem worldwide and in the United States as its incidence has increased substantially within the past two decades. HCC therapy remains a challenge, primarily due to underlying liver disorders such as cirrhosis that determines treatment approach and efficacy. Activated hepatic stellate cells (A-HSCs) are the key cell types involved in hepatic fibrosis/cirrhosis. A-HSCs are important constituents of HCC tumor microenvironment (TME) and support tumor growth, chemotherapy resistance, cancer cell migration, and escaping immune surveillance. This makes A-HSCs an important therapeutic target in hepatic fibrosis/cirrhosis as well as in HCC. Although many studies have reported the role of A-HSCs in cancer generation and investigated the therapeutic potential of A-HSCs reversion in cancer arrest, not much is known about inactivated or quiescent HSCs (Q-HSCs) in cancer growth or arrest. Here we report that Q-HSCs resist cancer cell growth by inducing cytotoxicity and enhancing chemotherapy sensitivity. We observed that the conditioned media from Q-HSCs (Q-HSCCM) induces cancer cell death through a caspase-independent mechanism that involves an increase in apoptosis-inducing factor expression, nuclear localization, DNA fragmentation, and cell death. We further observed that Q-HSCCM enhanced the efficiency of doxorubicin, as measured by cell viability assay. Exosomes present in the conditioned media were not involved in the mechanism, which suggests the role of other factors (proteins, metabolites, or microRNA) secreted by the cells. Identification and characterization of these factors are important in the development of effective HCC therapy.

Racial and Ethnic Disparities in Disease Severity on Admission Chest Radiographs among Patients Admitted with Confirmed Coronavirus Disease 2019: A Retrospective Cohort Study.

Background Disease severity on chest radiographs has been associated with higher risk of disease progression and adverse outcomes from coronavirus disease 2019 (COVID-19). Few studies have evaluated COVID-19-related racial and/or ethnic disparities in radiology. Purpose To evaluate whether non-White minority patients hospitalized with confirmed COVID-19 infection presented with increased severity on admission chest radiographs compared with White or non-Hispanic patients. Materials and Methods This single-institution retrospective cohort study was approved by the institutional review board. Patients hospitalized with confirmed COVID-19 infection between March 17, 2020, and April 10, 2020, were identified by using the electronic medical record (n = 326; mean age, 59 years ±17 [standard deviation]; male-to-female ratio: 188:138). The primary outcome was the severity of lung disease on admission chest radiographs, measured by using the modified Radiographic Assessment of Lung Edema (mRALE) score. The secondary outcome was a composite adverse clinical outcome of intubation, intensive care unit admission, or death. The primary exposure was the racial and/or ethnic category: White or non-Hispanic versus non-White (ie, Hispanic, Black, Asian, or other). Multivariable linear regression analyses were performed to evaluate the association between mRALE scores and race and/or ethnicity. Results Non-White patients had significantly higher mRALE scores (median score, 6.1; 95% confidence interval [CI]: 5.4, 6.7) compared with White or non-Hispanic patients (median score, 4.2; 95% CI: 3.6, 4.9) (unadjusted average difference, 1.8; 95% CI: 0.9, 2.8; P < .01). For both White (adjusted hazard ratio, 1.3; 95% CI: 1.2, 1.4; P < .001) and non-White (adjusted hazard ratio, 1.2; 95% CI: 1.1, 1.3; P < .001) patients, increasing mRALE scores were associated with a higher likelihood of experiencing composite adverse outcome with no evidence of interaction (P = .16). Multivariable linear regression analyses demonstrated that non-White patients presented with higher mRALE scores at admission chest radiography compared with White or non-Hispanic patients (adjusted average difference, 1.6; 95% CI: 0.5, 2.7; P < .01). Adjustment for hypothesized mediators revealed that the association between race and/or ethnicity and mRALE scores was mediated by limited English proficiency (P < .01). Conclusion Non-White patients hospitalized with coronavirus disease 2019 infection were more likely to have a higher severity of disease on admission chest radiographs than White or non-Hispanic patients, and increased severity was associated with worse outcomes for all patients. © RSNA, 2020 Online supplemental material is available for this article.

Lung apical findings in coronavirus disease (COVID-19) infection on neck and cervical spine CT.

PURPOSE: To evaluate the prevalence and features of lung apical findings on neck and cervical spine CTs performed in patients with COVID-19. METHODS: This was a retrospective, IRB-approved study performed at a large academic hospital in the USA. Between March 3, 2020, and May 6, 2020, 641 patients with COVID-19 infection diagnosed by RT-PCR received medical care at our institution. A small cohort of patients with COVID-19 infection underwent neck or cervical spine CT imaging for indications including stroke, trauma, and neck pain. The lung apices included in the field of view on these CT scans were reviewed for the presence of findings suspicious for COVID-19 pneumonia, including ground-glass opacities, consolidation, or crazy-paving pattern. The type and frequency of these findings were recorded and correlated with clinical information including age, gender, and symptoms. RESULTS: Thirty-four patients had neck or spine CTs performed before or concurrently with a chest CT. Of this group, 17 (50%) had unknown COVID-19 status at the time of neck or spine imaging and 10 (59%) of their CT studies had findings in the lung apices consistent with COVID-19 pneumonia. CONCLUSION: Lung apical findings on cervical spine or neck CTs consistent with COVID-19 infection are common and may be encountered on neuroimaging performed for non-respiratory indications. For these patients, the emergency radiologist may be the first physician to suspect underlying COVID-19 infection.

Effects of yeast culture supplementation and the ratio of non-structural carbohydrate to fat on growth performance, carcass traits and the fatty acid profile of the longissimus dorsi muscle in lambs.

The effects of yeast culture (YC) supplementation and the dietary ratio of non-structural carbohydrate to fat (NSCFR) on growth performance, carcass traits and fatty acid profile of the longissimus dorsi (LD) muscle in lambs were determined in a 2 × 3 full factorial experiment. Thirty-six Small-tailed Han lambs were randomly divided into six groups with six replicates per group. The lambs were fed one of the six pelleted total mixed rations (TMRs) for 60 days after 15 adaption days. The six rations were formed by two NSCFRs (11.37 and 4.57) and three YC supplementation levels (0, 0.8 and 2.3 g/kg dietary dry matter). The average daily gain (ADG), dry matter intake (DMI) and feed conversion ratio (FCR) data of each lamb were recorded and calculated. All the lambs were slaughtered for determining carcass traits and fatty acid profile of the LD muscle. DMI was significantly increased (p < 0.05) in a quadratic fashion with 0.8 g/kg of YC supplementation. Carcass weight (CW) and dressing percentage (DP) were significantly increased (p < 0.05) in a linear fashion with 2.3 g/kg of YC supplementation. Animals fed with high-NSCFR diet had higher (p < 0.05) contents of myristoleic acid (C14:1), pentadecanoic acid (C15:0) and cis-10-heptadecenoic acid (C17:1), and lower (p < 0.05) stearic acid (C18:0) content in LD muscle than those fed with low-NSCFR diet. Moreover, ADG, growth rate (GR), backfat thickness (BFT), percentages of crude fat (CF) and crude protein (CP), SFAs, MUFAs and PUFAs in LD muscle, were significantly affected (p < 0.05) by interaction of dietary NSCFR and supplemental YC level. Overall, YC not only improved the growth performance and carcass traits of the animals but also modified the fatty acid profile of the LD muscle. Furthermore, the effects of YC supplementation may depend on dietary compositions.

Mechanisms of Functional Hypoconnectivity in the Medial Prefrontal Cortex of Mecp2 Null Mice.

Frontal cortical dysfunction is thought to contribute to cognitive and behavioral features of autism spectrum disorders; however, underlying mechanisms are poorly understood. The present study sought to define how loss of Mecp2, the gene mutated in Rett syndrome (RTT), disrupts function in the murine medial prefrontal cortex (mPFC) using acute brain slices and behavioral testing. Compared with wildtype, pyramidal neurons in the Mecp2 null mPFC exhibit significant reductions in excitatory postsynaptic currents, the duration of excitatory UP-states, evoked population activity, and the ratio of NMDA:AMPA currents, as well as an increase in the relative fraction of NR2B currents. These functional changes are associated with reductions in the density of excitatory dendritic spines, the ratio of vesicular glutamate to GABA transporters and GluN1 expression. In contrast to recent reports on circuit defects in other brain regions, we observed no effect of Mecp2 loss on inhibitory synaptic currents or expression of the inhibitory marker parvalbumin. Consistent with mPFC hypofunction, Mecp2 nulls exhibit respiratory dysregulation in response to behavioral arousal. Our data highlight functional hypoconnectivity in the mPFC as a potential substrate for behavioral disruption in RTT and other disorders associated with reduced expression of Mecp2 in frontal cortical regions.

Rescue of behavioral and EEG deficits in male and female Mecp2-deficient mice by delayed Mecp2 gene reactivation.

Mutations of the X-linked gene encoding methyl CpG binding protein type 2 (MECP2) are the predominant cause of Rett syndrome, a severe neurodevelopmental condition that affects primarily females. Previous studies have shown that major phenotypic deficits arising from MeCP2-deficiency may be reversible, as the delayed reactivation of the Mecp2 gene in Mecp2-deficient mice improved aspects of their Rett-like phenotype. While encouraging for prospective gene replacement treatments, it remains unclear whether additional Rett syndrome co-morbidities recapitulated in Mecp2-deficient mice will be similarly responsive to the delayed reintroduction of functional Mecp2. Here, we show that the delayed reactivation of Mecp2 in both male and female Mecp2-deficient mice rescues established deficits in motor and anxiety-like behavior, epileptiform activity, cortical and hippocampal electroencephalogram patterning and thermoregulation. These findings indicate that neural circuitry deficits arising from the deficiency in Mecp2 are not engrained, and provide further evidence that delayed restoration of Mecp2 function can improve a wide spectrum of the Rett-like deficits recapitulated by Mecp2-deficient mice.