How BDNF affects working memory in acute sleep deprivation: The mediating role of spontaneous brain activity.

The brain-derived neurotrophic factor (BDNF) mediates the plasticity associated with memory processing, and compensatorily increases after acute sleep deprivation (SD). However, whether the altered spontaneous brain activity mediates the association between BDNF and working memory in SD remains unknown. Here, we aimed to probe the mediating role of the spontaneous brain activity between plasma BDNF and WM function in SD. A total of 30 healthy subjects with regular sleep were enrolled in this study. Resting-sate functional magnetic resonance imaging (fMRI) scans and the peripheral blood were collected before and after 24 h SD. All participants also received n-back task assessing working memory (WM) performance. The amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were calculated to reflect the intensity of regional spontaneous brain activity. Plasma BDNF was measured by sandwich ELISA. Our results revealed a significant decline in WM and increase in plasma BDNF level after SD, and negative association between the changed WM performance and plasma BDNF level. Specially, the ALFF of the left inferior parietal cortex and right inferior frontal cortex, and fALFF of the left anterior cingulate and medial prefrontal cortex and left posterior opercular cortex regulated the association between the BDNF and one-back reaction time respectively. Our results suggest that the association between BDNF and working memory may be mediated through regional spontaneous brain activity involving in the cerebral cortex, which may provide new sight into the interaction between neurotrophic factors and cognition, and potential targets for noninvasive brain stimulation on WM decline after acute SD.

Correlation of mir-221-3p differential expression with clinical characteristics of gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is one of the most common digestive malignancies. Although miR-221-3p was defined as a novel biomarker in many types of cancer, the relationship between its expression differences and the clinicopathological characteristics and prognosis of GC patients was yet to be fully understood. METHODS AND RESULTS: TCGA database was utilized to predict the potential biological function of miR-221-3p in GC. QRT-PCR and RNA FISH were performed to detect the expression levels of miR-221-3p in GC. The miR-221-3p expression levels in GC tissues and cells were significantly higher than those in paracancerous tissues (p < 0.001) and normal gastric mucosal cells (p < 0.05). Higher expression levels of miR-221-3p were associated with tumor diameter ≥ 4 cm (χ2 = 5.519, p = 0.019), cTNM stage (III + IV) (χ2 = 28.013, p = 0.000), lymph node metastasis (χ2 = 23.272, p = 0.000) and distant metastasis (χ2 = 7.930, p = 0.005). Kaplan-Meier survival analysis showed a better prognosis for GC patients with miR-221-3p low expression(HR = 4.520, 95% CI: 1.844-11.075). CONCLUSIONS: miR-221-3p is highly expressed in GC tissues, which plays an important role in tumorigenesis, invasion and metastasis. miR-221-3p may become an important biomarker and potential molecular therapeutic target for patients with GC.

Screening of Deoxynivalenol Cyclic Heptapeptide Mimotope Antigen.

In this study, phage clones that can bind to DON were selected from the phage cyclohepta peptide library by screening through the principle of solid-phase affinity, and mimotope were synthesized to replace the DON toxin standard to establish a green low toxicity detection system. The author conducted four rounds of screening in the phage cyclic heptapeptide library with DON-10a1a monoclonal antibody as the target molecule. Then 38 phage clones were selected and validated, and the results showed that 35 of them could bind to the DON-10a1a monoclonal antibody and were inhibited by DON toxin. Finally, the DNA was extracted and sequenced to obtain 6 different DNA sequences, which were named D1-D6 respectively. The peptides synthesized according to the corresponding amino acid sequences can replace DON toxin to establish a series of green and low toxicity assays.

Dysfunction of large-scale brain networks underlying cognitive impairments in shift work disorder.

It has been demonstrated that shift work can affect cognitive functions. Several neuroimaging studies have revealed altered brain function and structure for patients with shift work disorder (SWD). However, knowledge on the dysfunction of large-scale brain networks underlying cognitive impairments in shift work disorder is limited. This study aims to identify altered functional networks associated with cognitive declines in shift work disorder, and to assess their potential diagnostic value. Thirty-four patients with shift work disorder and 36 healthy controls (HCs) were recruited to perform the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and resting-state functional scans. After surface-based preprocessing, we calculated within- and between-network functional connectivity (FC) using the Dosenbach atlas. Moreover, correlation analysis was done between altered functional connectivity of large-scale brain networks and scores of cognitive assessments in patients with shift work disorder. Finally, we established a classification model to provide features for patients with shift work disorder concerning the disrupted large-scale networks. Compared with healthy controls, increased functional connectivity within-networks across the seven brain networks, and between-networks involving ventral attention network (VAN)-subcortical network (SCN), SCN-frontoparietal network (FPN), and somatosensory network (SMN)-SCN were observed in shift work disorder. Decreased functional connectivity between brain networks was found in shift work disorder compared with healthy controls, including visual network (VN)-FPN, VN-default mode network (DMN), SMN-DMN, dorsal attention network (DAN)-DMN, VAN-DMN, and FPN-DMN. Furthermore, the altered functional connectivity of large-scale brain networks was significantly correlated with scores of immediate memory, visuospatial, and delayed memory in patients with shift work disorder, respectively. Abnormal functional connectivity of large-scale brain networks may play critical roles in cognitive dysfunction in shift work disorder. Our findings provide new evidence to interpret the underlying neural mechanisms of cognitive impairments in shift work disorder.

Bcl-2 Antagonist Obatoclax Reactivates Latent HIV-1 via the NF-κB Pathway and Induces Latent Reservoir Cell Apoptosis in Latently Infected Cells.

The implementation of combined antiretroviral therapy (cART) has rendered HIV-1 infection clinically manageable and efficiently improves the quality of life for patients with AIDS. However, the persistence of a latent HIV-1 reservoir is a major obstacle to achieving a cure for AIDS. A "shock and kill" strategy aims to reactivate latent HIV and then kill it by the immune system or cART drugs. To date, none of the LRA candidates has yet demonstrated effectiveness in achieving a promising functional cure. Interestingly, the phosphorylation and activation of antiapoptotic Bcl-2 protein induce resistance to apoptosis during HIV-1 infection and the reactivation of HIV-1 latency in central memory CD4+ T cells from HIV-1-positive patients. Therefore, a Bcl-2 antagonist might be an effective LRA candidate for HIV-1 cure. In this study, we reported that a pan-Bcl-2 antagonist obatoclax induces HIV-1 reactivation in latently infected cell lines in vitro and in PBMCs/CD4+ T cells of HIV-infected individuals ex vivo. Obatoclax promotes HIV-1 transcriptional initiation and elongation by regulating the NF-κB pathway. Obatoclax activates caspase 8 and does not induce the phosphorylation of the antiapoptotic protein Bcl-2 in latent HIV-1 infected cell lines. More importantly, it preferentially induces apoptosis in latently infected cells. In addition, obatoclax exhibited potent anti-HIV-1 activity on target cells. The abilities to reactivate latent HIV-1 reservoirs, inhibit HIV-1 infection, and induce HIV-1 latent cell apoptosis make obatoclax worth investigating for development as an ideal LRA for use in the "shock and kill" approach.

Puerarin Prevents Bisphenol S Induced Lipid Accumulation by Reducing Liver Lipid Synthesis and Promoting Lipid Metabolism in C57BL/6J Mice.

Bisphenol S (BPS) is an environmental pollutant that can accumulate in the human body and cause harm. Puerarin (PUE) is a flavonoid with anti-inflammatory and antioxidant effects. In this study, we used 50 mg/kg/d BPS as a poison and PUE as an intervention for model mice for 42 d. BPS exposure significantly increased the levels of the impairment of the mice's liver function, T-CHO, TG, LDL-C, ALT, and AST in the BPS group were significantly increased (p < 0.05). Additionally, BPS exposure caused inflammatory cell infiltration in the mice liver tissue and enhanced oxidative stress response, the level of MDA was significantly increased (p < 0.05). The expression of CD36 and pparγ was stimulated after BPS exposure. Moreover, the expression of cpt1a and cpt1b, which promote fatty acid oxidation, was downregulated. After PUE intervention, the levels of genes and proteins involved in lipid synthesis (PPARγ, SREBP1C, and FASN) and metabolism (Cpt1a, Cpt1b, and PPARα) in mice returned to those of the control group, or much higher than those in the BPS group. Therefore, we hypothesized that BPS causes lipid accumulation in the liver by promoting lipid synthesis and reducing lipid metabolism, whereas PUE reduces lipid synthesis and promotes lipid metabolism. Conclusively, our results imply that long-term exposure to BPS in mice affects liver lipid metabolism and that PUE intervention could maintain the liver function of mice at normal metabolic levels.

Phenothiazines Inhibit SARS-CoV-2 Entry through Targeting Spike Protein.

Novel coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and continues to threaten humanity due to the persistent emergence of new variants. Therefore, developing more effective and broad-spectrum therapeutic and prophylactic drugs against infection by SARS-CoV-2 and its variants, as well as future emerging CoVs, is urgently needed. In this study, we screened several US FDA-approved drugs and identified phenothiazine derivatives with the ability to potently inhibit the infection of pseudotyped SARS-CoV-2 and distinct variants of concern (VOCs), including B.1.617.2 (Delta) and currently circulating Omicron sublineages XBB and BQ.1.1, as well as pseudotyped SARS-CoV and MERS-CoV. Mechanistic studies suggested that phenothiazines predominantly inhibited SARS-CoV-2 pseudovirus (PsV) infection at the early stage and potentially bound to the spike (S) protein of SARS-CoV-2, which may prevent the proteolytic cleavage of the S protein, thereby exhibiting inhibitory activity against SARS-CoV-2 infection. In summary, our findings suggest that phenothiazines can serve as a potential broad-spectrum therapeutic drug for the treatment of SARS-CoV-2 infection as well as the infection of future emerging human coronaviruses (HCoVs).

Stelleratenoids A-F, macrocyclic daphnane orthoesters with anti-HIV activity from the roots of Stellera chamaejasme L.

Six undescribed macrocyclic daphnane orthoesters, stelleratenoids A-F (1-6), were isolated from the roots of Stellera chamaejasme L. Their structures were elucidated by extensive spectroscopic analyses, including HRESIMS and NMR spectra. Compound 1 features an unusual terminal double bond at C-2/C-19 in the 1α-alkyldaphnane lactone skeleton. Compounds 2-4 are unique in the presence of different long chain fatty acyl groups. Compounds 5 and 6 are unique examples of modified macrocyclic daphnane diterpenoids. All the isolates were evaluated for anti-HIV activity in MT-2 cells. Among them, compounds 1, 5 and 6 exhibited highly potent anti-HIV activity with EC50 values of 66.70, 10.62 and 55.10 nM, respectively, possessing high potential to develop new anti-HIV drugs.

Bisphenol S induces oxidative stress-mediated impairment of testosterone synthesis by inhibiting the Nrf2/HO-1 signaling pathway.

Bisphenol S (BPS) is an environmental endocrine disruptor widely used in industrial production. BPS induces oxidative stress and exhibits male reproductive toxicity in mice, but the mechanisms by which BPS impairs steroid hormone synthesis are not fully understood. Nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 signaling is a key pathway in improving cellular antioxidant defense capacities. Therefore, this study explored the effects of exposure to BPS on testosterone synthesis in adult male mice and its mechanisms with regard to the Nrf2/HO-1 signaling pathway. Adult male C57BL/6 mice were orally exposed to BPS (2, 20, and 200 mg/kg BW) with sesame oil as a vehicle (0.1 ml/10 g BW) per day for 28 consecutive days. The results showed that compared with the control group, serum testosterone levels were substantially reduced in the 20 and 200 mg/kg BPS treatment groups, and testicular testosterone levels were reduced in all BPS treatment groups. These changes were accompanied by a prominent decrease in the expression levels of testosterone synthesis-related enzymes (STAR, CYP11A1, CYP17A1, HSD3B1, and HSD17B3) in the mouse testis. In addition, BPS induced oxidative stress in the testis by upregulating the messenger RNA and protein levels of Keap1 and downregulating the levels of Nrf2, HO-1, and downstream antioxidant enzymes (CAT, SOD1, and Gpx4). In summary, our results indicate that exposure of adult male mice to BPS can inhibit Nrf2/HO-1 signaling and antioxidant enzyme activity, which induces oxidative stress and thereby may impair testosterone synthesis in testicular tissues, leading to reproductive damage.

Constructing metagenome-assembled genomes for almost all components in a real bacterial consortium for binning benchmarking.

BACKGROUND: So far, a lot of binning approaches have been intensively developed for untangling metagenome-assembled genomes (MAGs) and evaluated by two main strategies. The strategy by comparison to known genomes prevails over the other strategy by using single-copy genes. However, there is still no dataset with all known genomes for a real (not simulated) bacterial consortium yet. RESULTS: Here, we continue investigating the real bacterial consortium F1RT enriched and sequenced by us previously, considering the high possibility to unearth all MAGs, due to its low complexity. The improved F1RT metagenome reassembled by metaSPAdes here utilizes about 98.62% of reads, and a series of analyses for the remaining reads suggests that the possibility of containing other low-abundance organisms in F1RT is greatly low, demonstrating that almost all MAGs are successfully assembled. Then, 4 isolates are obtained and individually sequenced. Based on the 4 isolate genomes and the entire metagenome, an elaborate pipeline is then in-house developed to construct all F1RT MAGs. A series of assessments extensively prove the high reliability of the herein reconstruction. Next, our findings further show that this dataset harbors several properties challenging for binning and thus is suitable to compare advanced binning tools available now or benchmark novel binners. Using this dataset, 8 advanced binning algorithms are assessed, giving useful insights for developing novel approaches. In addition, compared with our previous study, two novel MAGs termed FC8 and FC9 are discovered here, and 7 MAGs are solidly unearthed for species without any available genomes. CONCLUSION: To our knowledge, it is the first time to construct a dataset with almost all known MAGs for a not simulated consortium. We hope that this dataset will be used as a routine toolkit to complement mock datasets for evaluating binning methods to further facilitate binning and metagenomic studies in the future.

The BDNF-TrkB-CREB Signalling Pathway Is Involved in Bisphenol S-Induced Neurotoxicity in Male Mice by Regulating Methylation.

Bisphenol S (BPS), the most common substitute for bisphenol A in manufacturing, is associated with neurotoxicity, but its molecular mechanisms are unclear. Here, we studied the role of the BDNF-TrkB-CREB (brain-derived neurotrophic factor-tropomyosin-related kinase B-CAMP response element-binding protein) signalling pathway in bisphenol S-induced neurotoxicity via methylation regulation in male C57BL/6 mice. The mice were treated with sesame oil or 2, 20 and 200 mg/kg body weight BPS for 28 consecutive days, and the hippocampus was extracted. We recorded the body weight, organ index, and hippocampal pathology and ultrastructure of the mice. The BDNF, TrkB, CREB, phosphorylated (p)-CREB, DNMTs (DNA methyltransferases) levels were determined by qRT-PCR and/or Western blotting. BDNF promoter IV methylation level was detected by bisulfite sequencing PCR. BPS damaged the mouse hippocampus ultrastructure and reduced the number of synapses. Further, it increased the methylation rate of BDNF promoter IV; downregulated BDNF, CREB, p-CREB/CREB and DNMT1 expression; and upregulated DNMT3a and DNMT3b expression. Therefore, we speculate that the BDNF-TrkB-CREB pathway may be involved in BPS-induced neurotoxicity in male mice by regulating methylation.

FRAGTE2: An Enhanced Algorithm to Pre-Select Closely Related Genomes for Bacterial Species Demarcation.

We previously reported on FRAGTE (hereafter termed FRAGTE1), a promising algorithm for sieving (pre-selecting genome pairs for whole-genome species demarcation). However, the overall amount of pairs sieved by FRAGTE1 is still large, requiring seriously unaffordable computing cost, especially for large datasets. Here, we present FRAGTE2. Tests on simulated genomes, real genomes, and metagenome-assembled genomes revealed that (i) FRAGTE2 outstandingly reduces ~50-60.10% of the overall amount of pairs sieved by FRAGTE1, dramatically decreasing the computing cost required for whole-genome species demarcation afterward; (ii) FRAGTE2 shows superior sensitivity than FRAGTE1; (iii) FRAGTE2 shows higher specificity than FRAGTE1; and (iv) FRAGTE2 is faster than or comparable with FRAGTE1. Besides, FRAGTE2 is independent of genome completeness, the same as FRAGTE1. We therefore recommend FRAGTE2 tailored for sieving to facilitate species demarcation in prokaryotes.

A synthetic resveratrol analog termed Q205 reactivates latent HIV-1 through activation of P-TEFb.

The persistence of HIV-1 latent reservoir creates the major obstacle toward an HIV-1 cure. The "shock and kill" strategy aims to reverse HIV-1 proviral latency using latency-reversing agents (LRAs), thus boosting immune recognition and clearance to residual infected cells. Unfortunately, to date, none of these tested LRA candidates has been demonstrated effectiveness and/or safety in reactivation HIV-1 latency. The discovery and development of effective, safe and affordable LRA candidates are urgently needed for creating an HIV-1 functional cure. Here, we designed and synthesized a series of small-molecule phenoxyacetic acid derivatives based on the resveratrol scaffold and found one of them, named 5, 7-dimethoxy-2-(5-(methoxymethyl) furan-2-yl) quinazolin-4(3H)-one (Q205), effectively reactivated latent HIV-1 in latent HIV-1-infected cells without a corresponding increase in induction of potentially damaging cytokines. The molecular mechanism of Q205 is shown to increase the phosphorylation of the CDK9 T-loop at position Thr186, dissociate positive transcription elongation factor b (P-TEFb) from BRD4, and promote the Tat-mediated HIV-1 transcription and RNA polymerase II (RNAPII) C-terminal domain (CTD) on Ser (CTD-Ser2P) to bind to the HIV-1 promoter. This study provides a unique insight into resveratrol modified derivatives as promising leads for preclinical LRAs, which in turn may help toward inhibitor design and chemical optimization for improving HIV-1 shock-and kill-based efforts.

A New Small-Molecule Compound, Q308, Silences Latent HIV-1 Provirus by Suppressing Tat- and FACT-Mediated Transcription.

Eliminating the latent HIV reservoir remains a difficult problem for creating an HIV functional cure or achieving remission. The "block-and-lock" strategy aims to steadily suppress transcription of the viral reservoir and lock the HIV promoter in deep latency using latency-promoting agents (LPAs). However, to date, most of the investigated LPA candidates are not available for clinical trials, and some of them exhibit immune-related adverse reactions. The discovery and development of new, active, and safe LPA candidates for an HIV cure are necessary to eliminate residual HIV-1 viremia through the block-and-lock strategy. In this study, we demonstrated that a new small-molecule compound, Q308, silenced the HIV-1 provirus by inhibiting Tat-mediated gene transcription and selectively downregulating the expression levels of the facilitated chromatin transcription (FACT) complex. Strikingly, Q308 induced the preferential apoptosis in HIV-1 latently infected cells, indicating that Q308 may reduce the size of the viral reservoir and thus further prevent viral rebound. These findings highlight that Q308 is a novel and safe anti-HIV-1 inhibitor candidate for a functional cure.

UHRF1 Suppresses HIV-1 Transcription and Promotes HIV-1 Latency by Competing with p-TEFb for Ubiquitination-Proteasomal Degradation of Tat.

HIV-1 remains incurable due to viral reservoirs, which lead to durably latent HIV infection. Identifying novel host factors and deciphering the molecular mechanisms involved in the establishment and maintenance of latency are critical to discover new targets for the development of novel anti-HIV agents. Here, we show that ubiquitin-like with PHD and RING finger domain 1 (UHRF1) modulates HIV-1 5'-long terminal repeat (LTR)-driven transcription of the viral genome as a novel HIV-1 restriction factor. Correspondingly, UHRF1 depletion reversed the latency of HIV-1 proviruses. Mechanistically, UHRF1 competed with positive transcription factor b (p-TEFb) for the binding to the cysteine-rich motifs of HIV-1 Tat via its TTD, PHD, and RING finger domains. Furthermore, UHRF1 mediated K48-linked ubiquitination and proteasomal degradation of Tat in RING-dependent ways, leading to the disruption of Tat/cyclin T1/CDK9 complex and consequential impediment of transcription elongation. In summary, our findings revealed that UHRF1 is an important mediator of HIV-1 latency by controlling Tat-mediated transcriptional activation, providing novel insights on host-pathogen interaction for modulating HIV-1 latency, beneficial for the development of anti-AIDS therapies. IMPORTANCE HIV-1 latency is systematically modulated by host factors and viral proteins. In our work, we identified a critical role of host factor ubiquitin-like with PHD and RING finger domain 1 (UHRF1) in HIV-1 latency via the modulation of the viral protein Tat stability. By disrupting the Tat/cyclin T1/CDK9 complex, UHRF1 promotes the suppression of HIV-1 transcription and maintenance of HIV-1 latency. Our findings provide novel insights in controlling Tat expression via host-pathogen interaction for modulating HIV-1 latency. Based on our results, modulating UHRF1 expression or activity by specific inhibitors is a potential therapeutic strategy for latency reversal in HIV-1 patients.

CPI-637 as a Potential Bifunctional Latency-Reversing Agent That Targets Both the BRD4 and TIP60 Proteins.

The failure of highly active antiretroviral therapy (HAART) has been largely responsible for the existence of latent human immunodeficiency virus type 1 (HIV-1) reservoirs. The "shock and kill" strategy was confirmed to reactivate HIV-1 latent reservoirs by latency-reversing agents (LRAs) for accelerated HIV-1 clearance. However, a single LRA might be insufficient to induce HIV-1 reactivation from latency due to the complexity of the multiple signaling regulatory pathways that establish the HIV-1 latent reservoir. Therefore, combinations of LRAs or dual-mechanism LRAs are urgently needed to purge the latent reservoirs. We demonstrate here for the first time that a dual-target inhibitor with a specific suppressive effect on both BRD4 and TIP60, CPI-637, could reactivate latent HIV-1 in vitro by permitting Tat to bind positive transcription elongation factor b (P-TEFb) and assembling Tat-super-elongation complex (SEC) formation. In addition, CPI-637-mediated TIP60 downregulation further stimulated BRD4 dissociation from the HIV-1 long terminal repeat (LTR) promoter, allowing Tat to more effectively bind P-TEFb compared to BRD4 inhibition alone. Much more importantly, CPI-637 exerted a potent synergistic effect but alleviated global T cell activation and blocked viral spread to uninfected bystander CD4+ T cells with minimal cytotoxicity. Our results indicate that CPI-637 opens up the prospect of novel dual-target inhibitors for antagonizing HIV-1 latency and deserves further investigation for development as a promising LRA with a "shock and kill" strategy.

Ultrasonographic optic nerve sheath diameter correlation with ICP and accuracy as a tool for noninvasive surrogate ICP measurement in patients with decompressive craniotomy.

OBJECTIVE: Increased intracranial pressure (ICP) results in enlarged optic nerve sheath diameter (ONSD). In this study the authors aimed to assess the association of ONSD and ICP in severe traumatic brain injury (TBI) after decompressive craniotomy (DC). METHODS: ONSDs were measured by ocular ultrasonography in 40 healthy control adults. ICPs were monitored invasively with a microsensor at 6 hours and 24 hours after DC operation in 35 TBI patients. ONSDs were measured at the same time in these patients. Patients were assigned to 3 groups according to ICP levels, including normal (ICP ≤ 13 mm Hg), mildly elevated (ICP = 14-22 mm Hg), and severely elevated (ICP > 22 mm Hg) groups. ONSDs were compared between healthy control adults and TBI cases with DC. Then, the association of ONSD with ICP was analyzed using Pearson's correlation coefficient, linear regression analysis, and receiver operator characteristic curves. RESULTS: Seventy ICP measurements were obtained among 35 TBI patients after DC, including 25, 27, and 18 measurements in the normal, mildly elevated, and severely elevated ICP groups, respectively. Mean ONSDs were 4.09 ± 0.38 mm in the control group and 4.92 ± 0.37, 5.77 ± 0.41, and 6.52 ± 0.44 mm in the normal, mildly elevated, and severely elevated ICP groups, respectively (p < 0.001). A significant linear correlation was found between ONSD and ICP (r = 0.771, p < 0.0001). Enlarged ONSD was a robust predictor of elevated ICP. With an ONSD cutoff of 5.48 mm (ICP > 13 mm Hg), sensitivity and specificity were 91.1% and 88.0%, respectively; a cutoff of 5.83 mm (ICP > 22 mm Hg) yielded sensitivity and specificity of 94.4% and 81.0%, respectively. CONCLUSIONS: Ultrasonographic ONSD is strongly correlated with invasive ICP measurements and may serve as a sensitive and noninvasive method for detecting elevated ICP in TBI patients after DC.