Multifocal strokes and vision loss from PDLLA filler injections.

BACKGROUND: Poly-D, L-lactic acid (PDLLA) is increasingly used as a commercial dermal filler due to its lasting cosmetic properties. Consequently, PDLLA-related vascular complications are increasingly recognized and described. Herein, we describe the first known occurrence of multifocal strokes from the use of PDLLA as a cosmetic dermal filler, and discuss the mechanisms facilitating PDLLA's entry into the intracranial arterial system. CASE PRESENTATION: A middle-aged female presented with acute vision loss of both eyes immediately after dermal injections of PDLLA to her nasolabial folds and infraorbital regions. There were no additional neurological deficits. Dilated fundal examination revealed retinal edema bilaterally, with deposition of filler material in the retinal arteries. Magnetic resonance imaging of her brain and orbits demonstrated multifocal strokes (left caudate head, right medial frontal lobe) and ischemia of the left optic nerve. The temporal proximity of the dermal injections to her symptoms, guided by fundal examination and neuroimaging findings, allowed us to attribute her strokes and ischemic optic neuropathy to PDLLA's entry into, and embolism within, the intracranial arterial system. She was treated with hyperbaric oxygen therapy and experience improvement to her right eye's vision, although poor vision persisted in her left eye. CONCLUSION: While PDLLA is generally considered safe, its increasing use as a cosmetic filler renders it crucial for physicians to be cognizant of its vascular complications, especially when early recognition and treatment are essential in mitigating their devastating ramifications.

Atmospheric Turbulence Aberration Correction Based on Deep Learning Wavefront Sensing.

In this paper, research was conducted on Deep Learning Wavefront Sensing (DLWS) neural networks using simulated atmospheric turbulence datasets, and a novel DLWS was proposed based on attention mechanisms and Convolutional Neural Networks (CNNs). The study encompassed both indoor experiments and kilometer-range laser transmission experiments employing DLWS. In terms of indoor experiments, data were collected and training was performed on the platform built by us. Subsequent comparative experiments with the Shack-Hartmann Wavefront Sensing (SHWS) method revealed that our DLWS model achieved accuracy on par with SHWS. For the kilometer-scale experiments, we directly applied the DLWS model obtained from the indoor platform, eliminating the need for new data collection or additional training. The DLWS predicts the wavefront from the beacon light PSF in real time and then uses it for aberration correction of the emitted laser. The results demonstrate a substantial improvement in the average peak intensity of the light spot at the target position after closed-loop correction, with a remarkable increase of 5.35 times compared to the open-loop configuration.

Cocaine-induced ischemia in prefrontal cortex is associated with escalation of cocaine intake in rodents.

Cocaine-induced vasoconstriction reduces blood flow, which can jeopardize neuronal function and in the prefrontal cortex (PFC) it may contribute to compulsive cocaine intake. Here, we used integrated optical imaging in a rat self-administration and a mouse noncontingent model, to investigate whether changes in the cerebrovascular system in the PFC contribute to cocaine self-administration, and whether they recover with detoxification. In both animal models, cocaine induced severe vasoconstriction and marked reductions in cerebral blood flow (CBF) in the PFC, which were exacerbated with chronic exposure and with escalation of cocaine intake. Though there was a significant proliferation of blood vessels in areas of vasoconstriction (angiogenesis), CBF remained reduced even after 1 month of detoxification. Treatment with Nifedipine (Ca2+ antagonist and vasodilator) prevented cocaine-induced CBF decreases and neuronal Ca2+ changes in the PFC, and decreased cocaine intake and blocked reinstatement of drug seeking. These findings provide support for the hypothesis that cocaine-induced CBF reductions lead to neuronal deficits that contribute to hypofrontality and to compulsive-like cocaine intake in addiction, and document that these deficits persist at least one month after detoxification. Our preliminary data showed that nifedipine might be beneficial in preventing cocaine-induced vascular toxicity and in reducing cocaine intake and preventing relapse.

Isolated Infarctions of the Conus Medullaris: Clinical Features and Outcomes.

OBJECTIVE: This study aims to describe the clinical features and outcomes of patients with isolated infarctions of the conus medullaris, and to identify factors associated with poor functional outcomes. MATERIALS AND METHODS: We performed a systematic review and retrospective analysis on the clinical characteristics and outcomes of patients with isolated conus medullaris infarctions reported in literature over the past 30 years. RESULTS: We analyzed a total of 19 cases; 18 identified in literature from January 1991 to June 2021, together with our patient. Their median age was 56 years (range 28-79), with twice as many females as males. Pain was prominent at onset (15/19, 79%), only a third had vascular risk factors (7/19, 37%), and half had no significant preceding activities or events (9/19, 47%). Almost all experienced paraplegia or paraparesis (16/19, 84%), in which upper motor neuron features were rare (3/19, 16%). The underlying cause was unknown in half (10/19, 53%). Functional outcomes appeared fair, with nearly half being capable of unassisted ambulation (9/11, 82%). Patients with vascular risk factors (67% vs 13%, p = 0.024) or with identified underlying causes (78% vs 13%, p = 0.007) were less likely to walk unassisted. CONCLUSION: Isolated conus medullaris but should be considered in patients with acute cauda equina syndrome, especially in females. Patients with vascular risk factors, or with known causes of infarction, are less likely to walk unassisted. DWI sequences should be included in conventional MRI sequences when evaluating patients with acute cauda equina syndrome.

Idiopathic Intracranial Hypertension - Characteristic MRI Features.

We present the case of 24-year-old woman who presented with chronic headaches with features of raised intracranial pressure and bilateral papilledema. Brain magnetic resonance imaging revealed the characteristic features of idiopathic intracranial hypertension. A diagnosis supported by clinical features and other ancillary tests. These features are important for physicians to recognize early, so that timely treatment may prevent permanent complications from this rare but potentially sight-threatening headache.

Constructal Design of an Arrow-Shaped High Thermal Conductivity Channel in a Square Heat Generation Body.

A heat conduction model with an arrow-shaped high thermal conductivity channel (ASHTCC) in a square heat generation body (SHGB) is established in this paper. By taking the minimum maximum temperature difference (MMTD) as the optimization goal, constructal designs of the ASHTCC are conducted based on single, two, and three degrees of freedom optimizations under the condition of fixed ASHTCC material. The outcomes illustrate that the heat conduction performance (HCP) of the SHGB is better when the structure of the ASHTCC tends to be flat. Increasing the thermal conductivity ratio and area fraction of the ASHTCC material can improve the HCP of the SHGB. In the discussed numerical examples, the MMTD obtained by three degrees of freedom optimization are reduced by 8.42% and 4.40%, respectively, compared with those obtained by single and two degrees of freedom optimizations. Therefore, three degrees of freedom optimization can further improve the HCP of the SHGB. Compared the HCPs of the SHGBs with ASHTCC and the T-shaped one, the MMTD of the former is reduced by 13.0%. Thus, the structure of the ASHTCC is proven to be superior to that of the T-shaped one. The optimization results gained in this paper have reference values for the optimal structure designs for the heat dissipations of various electronic devices.

Complex Tannins Isolated from Jelly Fig Achenes Affect Pectin Gelation through Non-Specific Inhibitory Effect on Pectin Methylesterase.

Jelly fig (Ficus awkeotsang Makino) is used to prepare drinks and desserts in Asia, owing to the gelling capability of its pectin via endogenous pectin methylesterase (PE) catalyzation. Meanwhile, substances with PE inhibitory activity (SPEI) in jelly fig achenes (JFA) residue were noticed to be able to impede the gelation. In this study, we characterized and isolated SPEI from JFA by a series of PE inhibition-guided isolations. Crude aqueous extract of JFA residue was mixed with acetone, and 90% acetone-soluble matter was further fractionated by Diaion HP-20 chromatography. The retained fraction with dominant PE inhibitory activity was collected from 100% methanol eluate. Results from high-performance liquid chromatography mass spectrometry (HPLC/MS) and hydrolysis-induced chromogenic transition revealed the SPEI as complex tannins. Total tannins content was determined in each isolated fraction, and was closely related to PE inhibitory activity. In addition, SPEI in this study could inhibit activities of digestive enzymes in vitro and may, therefore, be assumed to act as non-specific protein binding agent.

Long-term optical imaging of neurovascular coupling in mouse cortex using GCaMP6f and intrinsic hemodynamic signals.

Cerebral hemodynamics are modulated in response to changes in neuronal activity, a process termed neurovascular coupling (NVC), which can be disrupted by neuropsychiatric diseases (e.g., stroke, Alzheimer's disease). Thus, there is growing interest to image long-term NVC dynamics with high spatiotemporal resolutions. Here, by combining the use of a genetically-encoded calcium indicator with optical techniques, we develop a longitudinal multimodal optical imaging platform (MIP) that enabled time-lapse tracking of NVC over a relatively large field of view in the mouse somatosensory cortex at single cell and single vessel resolutions. Specifically, GCaMP6f was used as marker of neuronal activity, which along with MIP allowed us to simultaneously measure the changes in neuronal [Ca2+]i fluorescence, cerebral blood flow velocity (CBFv) and hemodynamics longitudinally for more than eight weeks. We show that [Ca2+]i fluorescence was detectable one week post viral injection and the damage to local microvasculature and perfusion recovered two weeks after injection. By three weeks post viral injection, maximal neuronal and CBFv responses to hindpaw stimulations were observed. Moreover, single neuronal activation in response to hindpaw stimulation was consistently recorded, followed by ∼2 s delayed dilation of contiguous microvessels. Additionally, resting-state spontaneous neuronal and hemodynamic oscillations were detectable throughout the eight weeks of study. Our results demonstrate the capability of MIP for longitudinal investigation of the organization and plasticity of the neurovascular network during resting state and during stimulation-evoked neuronal activation at high spatiotemporal resolutions.

Versatile effects of bacterium-released membrane vesicles on mammalian cells and infectious/inflammatory diseases.

Gram-negative bacterium-released outer-membrane vesicles (OMVs) and Gram-positive bacterium-released membrane vesicles (MVs) share significant similarities with mammalian cell-derived MVs (eg, microvesicles and exosomes) in terms of structure and their biological activities. Recent studies have revealed that bacterial OMVs/MVs could (1) interact with immune cells to regulate inflammatory responses, (2) transport virulence factors (eg, enzymes, DNA and small RNAs) to host cells and result in cell injury, (3) enhance barrier function by stimulating the expression of tight junction proteins in intestinal epithelial cells, (4) upregulate the expression of endothelial cell adhesion molecules, and (5) serve as natural nanocarriers for immunogenic antigens, enzyme support and drug delivery. In addition, OMVs/MVs can enter the systemic circulation and induce a variety of immunological and metabolic responses. This review highlights the recent advances in the understanding of OMV/MV biogenesis and their compositional remodeling. In addition, interactions between OMVs/MVs and various types of mammalian cells (ie, immune cells, epithelial cells, and endothelial cells) and their pathological/preventive effects on infectious/inflammatory diseases are summarized. Finally, methods for engineering OMVs/MVs and their therapeutic potential are discussed.

Constructal Optimization for Cooling a Non-Uniform Heat Generating Radial-Pattern Disc by Conduction.

A heat conduction model in a radial-pattern disc by considering non-uniform heat generation (NUHG) is established in this paper. A series of high conductivity channels (HCCs) are attached on the rim of the disc and extended to its center. Constructal optimizations of the discs with constant and variable cross-sectional HCCs are carried out, respectively, and their maximum temperature differences (MTDs) are minimized based on analytical method and finite element method. Besides, the influences of the NUHG coefficient, HCC number and width coefficient on the optimal results are studied. The results indicate that the deviation of the optimal constructs obtained from the analytical method and finite element method are comparatively slight. When the NUHG coefficient is equal to 10, the minimum MTD of the disc with 25 constant cross-sectional HCCs is specifically reduced by 48.8% compared to that with 10 HCCs. As a result, the heat conduction performance (HCP) of the disc can be efficiently improved by properly increasing the number of HCCs. The minimum MTD of the disc with variable cross-sectional HCC is decreased by 15.0% when the width coefficient is changed from 1 to 4. Therefore, the geometry of variable cross-sectional HCC can be applied in the constructal design of the disc to a better heat transfer performance. The constructal results obtained by investigating the non-uniform heat generating case in this paper can contribute to the design of practical electronic device to a better heat transfer performance.

Transgenic Arabidopsis thaliana plants expressing a ß-1,3-glucanase from sweet sorghum (Sorghum bicolor†L.) show reduced callose deposition and increased tolerance to aluminium toxicity.

Seventy-one cultivars of sweet sorghum (Sorghum bicolor L.) were screened for aluminium (Al) tolerance by measuring relative root growth (RRG). Two contrasting cultivars, ROMA (Al tolerant) and POTCHETSTRM (Al sensitive), were selected to study shorter term responses to Al stress. POTCHETSTRM had higher callose synthase activity, lower ß-1,3-glucanase activity and more callose deposition in the root apices during Al treatment compared with ROMA. We monitored the expression of 12 genes involved in callose synthesis and degradation and found that one of these, SbGlu1 (Sb03g045630.1), which encodes a ß-1,3-glucanase enzyme, best explained the contrasting deposition of callose in ROMA and POTCHETSTRM during Al treatment. Full-length cDNAs of SbGlu1 was prepared from ROMA and POTCHETSTRM and expressed in Arabidopsis thaliana using the constitutive cauliflower mosaic virus (CaMV) 35S promoter. Independent transgenic lines displayed significantly greater Al tolerance than wild-type plants and vector-only controls. This phenotype was associated with greater total ß-1,3-glucanase activity, less Al accumulation and reduced callose deposition in the roots. These results suggest that callose production is not just an early indicator of Al stress in plants but likely to be part of the toxicity pathway that leads to the inhibition of root growth.

Quantitative imaging of microvascular blood flow networks in deep cortical layers by 1310 nm µODT.

There is growing interest in new neuroimage techniques that permit not only high-resolution quantification of cerebral blood flow velocity (CBFv) in capillaries, but also a large field of view to map the CBFv network dynamics. Such image capabilities are of great importance for decoding the functional difference across multiple cortical layers under stimuli. To tackle the limitation of optical penetration depth, we present a new ultrahigh-resolution optical coherence Doppler tomography (µODT) system at 1310 nm and compare it with a prior 800 nm µODT system for mouse brain 3D CBFv imaging. We show that the new 1310 nm µODT allows for dramatically increased depth (∼4 times) of quantitative CBFv imaging to 1.4 mm, thus covering the full thickness of the mouse cortex (i.e., layers I-VI). Interestingly, we show that such a unique 3D CBFv imaging capability allows identification of microcirculatory redistribution across different cortical layers resulting from repeated cocaine exposures.

[Sensitization of human colon cancer HT-29 cells to TRAIL-induced apoptosis by gambognic acid].

To investigate the effects of gambognic acid (GA) on TRAIL-induced apoptosis of cancer cells, human colon HT-29 cancer cells were treated with GA to promote apoptosis. Inhibition of the cell proliferation was measured with MTT assay and cell apoptosis was detected with formation of DNA ladders in agarose gel electrophoresis, and activation of caspase activity. The content of cytosolic reactive oxygen species (ROS) was measured with flow cytometry. The activities of Caspase-3, -8, -9 were detected using spectrophotometric assay. The levels of c-FLIP, CHOP, DR4 and DR5 in cells were tested by Western blot. Combination of GA (1 µg · mL(-1)) and TRAIL (40 ng · mL(-1)) significantly reduced proliferation and increased apoptosis of HT-29 cells over those induced by each agent alone. Percentage of apoptotic cells was increased to 45.5%. GA markedly enhanced the intracellular ROS generation. Expression of CHOP, DR4 and DR5 was up-regulated to 7.38, 5.41, and 4.85 times of the control group, respectively. GA promoted activation of Caspase-3, -8, and -9 by TRAIL (P<0.05). Furthermore, the expression of anti-apoptotic protein c-FLIP was down-regulated to 0.22 ± 0.08 times of the control group. In conclusion, GA sensitizes HT-29 cells to TRAIL-induced apoptosis by promoting ROS-activated ERS pathways, up-regulating of DR4 and DR5, and inhibiting c-FLIP expression.

[Study on Error Analysis of Nonlinear Function Coefficient of FAIMS].

The solution of ion mobility's nonlinear function coefficients α2 and α4 is the basis for achieving substance identification of High Field Asymmetric waveform Ion Mobility Spectrometry (FAIMS). Currently, nonlinear function coefficients α2 and α4 lack priors, meanwhile, existed solving results about α2 and α4 are deficient in error evaluation standard. In this article, acetone, isopropanol and 1, 2-dichlorobenzene were detected under different dispersion voltage by homemade FAIMS. In general, the spectrum peak of same sample at different dispersion voltage value is unique. Different dispersion voltage and corresponding compensation voltage value determines the value of α2 and α4. According to sample spectra at different dispersion voltage value, groups of spectral characteristics were obtained. Affirmatory number of data which were selected from multiple sets of compensation voltage value and dispersion voltage value, so that they were utilized to solved out lots of α2 and α4. Lots of factor have an effect on the accuracy of the solving results of α2 and α4, for instance, value of compensation voltage and dispersion voltage, style of fetching points of dispersion voltage, and so on. Comparing to other factors, style and amount of dispersion voltage is likely to control. By data analyzing huge amounts of α2 and α4 data, this paper explored their characteristic of distribution and correlation about them, research influence of number and method to fetch dispersion voltage detected points for error of solving results. After fitting frequency of α2 and α4, it was found that they conform to normal distribution, goodness of fitting exceed 0. 96, thus standard deviation of their distribution are able to evaluate error of solving results. In addition, a strong correlation exists between them, relevance of sample is -0. 977, -0. 968, -0. 992 respectively. With increasing of computing selected points, the corresponding error of solving results decrease. By comparing the standard deviation of method to fetch dispersion voltage detected points, found that detecting frequency in case of detecting maximum and the 70% of maximum of dispersion voltage value is lower at approximately same standard deviation, solving effect was optimized in unique fetching points style. Based on the premise of ensuring the accuracy of solving results of α2 and α4, it is obvious that reducing the frequency of detections for FAIMS effectively. It created favorable conditions for rapid field detection and precise spectral analysis.

Ultrasensitive detection of 3D cerebral microvascular network dynamics in vivo.

Despite widespread applications of multiphoton microscopy in microcirculation, its small field of view and inability to instantaneously quantify cerebral blood flow velocity (CBFv) in vascular networks limit its utility in investigating the heterogeneous responses to brain stimulations. Optical Doppler tomography (ODT) provides 3D images of CBFv networks, but it suffers poor sensitivity for measuring capillary flows. Here we report on a new method, contrast-enhanced ODT with Intralipid that significantly improves quantitative CBFv imaging of capillary networks by obviating the errors from long latency between flowing red blood cells (low hematocrit ~20% in capillaries). This enhanced sensitivity allowed us to measure the ultraslow microcirculation surrounding a brain tumor and the abnormal ingrowth of capillary flows in the tumor as well as in ischemia triggered by chronic cocaine in the mouse brain that could not be detected by regular ODT. It also enabled significantly enhanced sensitivity for quantifying the heterogeneous CBFv responses of vascular networks to acute cocaine exposure. Inasmuch as lipid emulsions are widely used for parenteral nutrition the Intralipid contrast method has translational potential for clinical applications.

Meta-analysis of 5-hydroxytryptamine type 2A receptor polymorphisms and migraine susceptibility.

Epidemiologic studies have investigated the association of polymorphisms in 5-hydroxytryptamine type 2A receptor (5HT2A) gene and migraine susceptibility, but the results of those studies are inconclusive. To obtain a more systematic estimation of the association, we conducted a comprehensive search to examine all the eligible studies of 5HT2A polymorphisms and migraine risk. The odd ratios (ORs) with 95% confidence intervals (CIs) were used to determine the strength of the association. Publication bias was analyzed by Begg's funnel plots. Seven eligible studies regarding 5HT2A T102C and A-1438G polymorphisms with 721 cases and 713 controls were included in this meta-analysis. Overall, no significant associations were found between 5HT2A T102C (for T vs. C: OR = 1.029, 95% CI = 0.870-1.217, p = 0.739; for TT vs. CC: OR = 1.083, 95% CI = 0.760-1.544, p = 0.657; for TT + TC vs. CC: OR = 1.066, 95% CI = 0.802-1.416, p = 0.662; for TT vs. TC + CC: OR = 1.017, 95% CI = 0.774-1.336, p = 0.904) or A-1438G (for T vs. C: OR = 0.996, 95% CI = 0.726-1.365, p = 0.979; for TT vs. CC: OR = 0.983, 95% CI = 0.511-1.891, p = 0.960; for TT + TC vs. CC: OR = 1.118, 95% CI = 0.654-1.910, p = 0.684; for TT vs. TC + CC: OR = 0.890, 95% CI = 0.528-1.499, p = 0.661) polymorphisms and migraine risk. The further subgroup analysis by ethnicity, assay and disease type also found no significant association using four genetic models. Meanwhile, the publication bias analysis suggests that there is no publication bias in these studies. In conclusion, our current meta-analysis implies that 5HT2A T102C and A-1438G polymorphisms may be not risk factors in the pathogenesis of migraine.

[Anaplastic lymphoma kinase fusion gene expression, clinical pathological characteristics and prognosis in 95 Chinese patients with non-small cell lung cancer].

OBJECTIVE: To examine the prevalence of anaplastic lymphoma kinase (ALK) fusion gene in Chinese patients with non-small cell lung cancer (NSCLC). METHODS: In this study, 95 patients with NSCLC and corresponding clinical information and formalin-fixed paraffin-embedded (FFPE) tissue blocks were included. Hematoxylin & eosin (HE) staining, conventional ALK immunochemistry (IHC) staining and intercalated antibody-enhanced polymer (iAEP) IHC staining, and dual-color split fluorescence in situ hybridization (FISH) for ALK fusion gene were performed. RESULTS: Eight ALK-positive cases were detected using anti-ALK immunohistochemistry with the iAEP method, and FISH analyses revealed 4 patients of them who harbored the ALK fusion gene (4.2%, 4/95), including 2 cases of female patients with solid signet-ring cell adenocarcinoma and 2 cases of male patients with adenosquamous carcinoma. The positive cases were all non-smokers without EGFR/KRAS mutations. Furthermore, the positive cases all survived, and the overall postsurgery survival time of 2 cases was more than 5 years. CONCLUSION: ALK IHC with the iAEP method is better than conventional ALK IHC, and the percentage of the positive cells is more important than that of the intensity. ALK translocations were infrequent in the entire NSCLC patient population (<5%) with better prognosis.

Inherited chromosomally-integrated human herpes virus 6 confounding test results in a patient with myelitis and optic neuritis - A case report.

A case of the 'perfect storm' of myelin oligodendrocyte glycoprotein (MOG) antibody-mediated myelitis, human herpesvirus 6 (HHV-6) reactivation, and COVID-19 infection was reported in 2021. This article reports a case of a similarly observed clinical triad, but with a different conclusion and explanation supported by laboratory test results and evidence from our literature review.

[Clinicopathologic features and prognostic factors of malignant phyllodes tumors].

OBJECTIVE: To study the clinicopathologic features of malignant phyllodes tumors (PT) by histopathologic analyses, immunohistochemical profiling and DNA content assay, and evaluation of the clinical outcome. METHODS: Ten patients with malignant PT from 1999 to 2013 who were treated by surgery were enrolled in this study. The morphologic characteristics were studied under light microscope, standard two-step EnVision method of immunohistochemical staining was used to assess the expression of CK5/6, CKpan, 34ß E12, desmin, p63, ER-α, PR, Ki-67, CD34, SMA, p53, p16, bcl-2 and CD117 in the tumors. The corresponding paraffin blocks were also used for flow cytometric DNA content assay. These data were correlated with the follow-up results. RESULTS: The median age of onset was 46.5 years old. The mean tumor size was 7.4 cm (2.0-25.0 cm). At the end of the follow-up period (22 to 125 months), there were tumor recurrences in 3/8 patients and the median time of recurrence was 24 months. Metastasis occurred in 3/8 patients who all died of the tumors. PT had heterogeneous histology, with stromal overgrowth with leaf-like projections, periductal stromal overgrowth, and most commonly, diffuse stromal overgrowth with sarcomatous differentiation. The mean positive index of Ki-67 was 11.4%. The stromal tumor cells were positive for CD34, SMA, p53, p16, and bcl-2 in 3/10, 9/10, 6/10, 8/10, and 4/10 cases, respectively. CD117,ER-α and PR were negative. Interpretable DNA histograms were obtained in nine cases with triploidy in two cases. CONCLUSIONS: The diagnosis of malignant PT should be considered based on the diversity of growth patterns and heterogeneous histology.Ki-67 and CD34 are valuable diagnostic and prognostic factors in patients with malignant PT. Tumors with diffuse stromal overgrowth, heterologous elements, Ki-67 ≥ 20% or aneuploidy are more likely to metastasize.