Piezo1 stretch-activated channel activity differs between murine bone marrow-derived and cardiac tissue-resident macrophages.

Macrophages (MΦ) play pivotal roles in tissue homeostasis and repair. Their mechanical environment has been identified as a key modulator of various cell functions, and MΦ mechanosensitivity is likely to be critical - in particular in a rhythmically contracting organ such as the heart. Cultured MΦ, differentiated in vitro from bone marrow (MΦBM), form a popular research model. This study explores the activity of mechanosensitive ion channels (MSC) in murine MΦBM and compares it to MSC activity in MΦ enzymatically isolated from cardiac tissue (tissue-resident MΦ; MΦTR). We show that MΦBM and MΦTR have stretch-induced currents, indicating the presence of functional MSC in their plasma membrane. The current profiles in MΦBM and in MΦTR show characteristics of cation non-selective MSC such as Piezo1 or transient receptor potential channels. While Piezo1 ion channel activity is detectable in the plasma membrane of MΦBM using the patch-clamp technique, or by measuring cytosolic calcium concentration upon perfusion with the Piezo1 channel agonist Yoda1, no Piezo1 channel activity was observed in MΦTR. The selective transient receptor potential vanilloid 4 (TRPV4) channel agonist GSK1016790A induces calcium entry in MΦTR and in MΦBM. In MΦ isolated from left-ventricular scar tissue 28 days after cryoablation, stretch-induced current characteristics are not significantly different compared to non-injured control tissue, even though scarred ventricular tissue is expected to be mechanically remodelled and to contain an altered composition of pre-existing cardiac and circulation-recruited MΦ. Our data suggest that the in vitro differentiation protocols used to obtain MΦBM generate cells that differ from MΦ recruited from the circulation during tissue repair in vivo. Further investigations are needed to explore MSC identity in lineage-traced MΦ in scar tissue, and to compare mechanosensitivity of circulating monocytes with that of MΦBM. KEY POINTS: Bone marrow-derived (MΦBM) and tissue resident (MΦTR) macrophages have stretch-induced currents, indicating expression of functional mechanosensitive channels (MSC) in their plasma membrane. Stretch-activated current profiles show characteristics of cation non-selective MSC; and mRNA coding for MSC, including Piezo1 and TRPV4, is expressed in murine MΦBM and in MΦTR. Calcium entry upon pharmacological activation of TRPV4 confirms functionality of the channel in MΦTR and in MΦBM. Piezo1 ion channel activity is detected in the plasma membrane of MΦBM but not in MΦTR, suggesting that MΦBM may not be a good model to study the mechanotransduction of MΦTR. Stretch-induced currents, Piezo1 mRNA expression and response to pharmacological activation are not significantly changed in cardiac MΦ 28 days after cryoinjury compared to sham operated mice.

Elevated phase amplitude coupling as a depression biomarker in epilepsy.

Depression is prevalent in epilepsy patients and their intracranial brain activity recordings can be used to determine the types of brain activity that are associated with comorbid depression. We performed case-control comparison of spectral power and phase amplitude coupling (PAC) in 34 invasively monitored drug resistant epilepsy patients' brain recordings. The values of spectral power and PAC for one-minute segments out of every hour in a patient's study were correlated with pre-operative assessment of depressive symptoms by Beck Depression Inventory-II (BDI). We identified an elevated PAC signal (theta-alpha-beta phase (5-25 Hz)/gamma frequency (80-100 Hz) band) that is present in high BDI scores but not low BDI scores adult epilepsy patients in brain regions implicated in primary depression, including anterior cingulate cortex, amygdala and orbitofrontal cortex. Our results showed the application of PAC as a network-specific, electrophysiologic biomarker candidate for comorbid depression and its potential as treatment target for neuromodulation.

Collagen IV differentially regulates planarian stem cell potency and lineage progression.

The extracellular matrix (ECM) provides a precise physical and molecular environment for cell maintenance, self-renewal, and differentiation in the stem cell niche. However, the nature and organization of the ECM niche is not well understood. The adult freshwater planarian Schmidtea mediterranea maintains a large population of multipotent stem cells (neoblasts), presenting an ideal model to study the role of the ECM niche in stem cell regulation. Here we tested the function of 165 planarian homologs of ECM and ECM-related genes in neoblast regulation. We identified the collagen gene family as one with differential effects in promoting or suppressing proliferation of neoblasts. col4-1, encoding a type IV collagen α-chain, had the strongest effect. RNA interference (RNAi) of col4-1 impaired tissue maintenance and regeneration, causing tissue regression. Finally, we provide evidence for an interaction between type IV collagen, the discoidin domain receptor, and neuregulin-7 (NRG-7), which constitutes a mechanism to regulate the balance of symmetric and asymmetric division of neoblasts via the NRG-7/EGFR pathway.

In-hospital outcomes in patients with and without epilepsy diagnosed with COVID-19-A cohort study.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is associated with mortality in persons with comorbidities. The aim of this study was to evaluate in-hospital outcomes in patients with COVID-19 with and without epilepsy. METHODS: We conducted a retrospective study of patients with COVID-19 admitted to a multicenter health system between March 15, 2020, and May 17, 2021. Patients with epilepsy were identified using a validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)/ICD-10-CM case definition. Logistic regression models and Kaplan-Meier analyses were conducted for mortality and non-routine discharges (i.e., not discharged home). An ordinary least-squares regression model was fitted for length of stay (LOS). RESULTS: We identified 9833 people with COVID-19 including 334 with epilepsy. On univariate analysis, people with epilepsy had significantly higher ventilator use (37.70% vs 14.30%, p < .001), intensive care unit (ICU) admissions (39.20% vs 17.70%, p < .001) mortality rate (29.60% vs 19.90%, p < .001), and longer LOS (12 days vs 7 days, p < .001). and fewer were discharged home (29.64% vs 57.37%, p < .001). On multivariate analysis, only non-routine discharge (adjusted odds ratio [aOR] 2.70, 95% confidence interval [CI] 2.00-3.70; p < .001) and LOS (32.50% longer, 95% CI 22.20%-43.60%; p < .001) were significantly different. Factors associated with higher odds of mortality in epilepsy were older age (aOR 1.05, 95% CI 1.03-1.08; p < .001), ventilator support (aOR 7.18, 95% CI 3.12-16.48; p < .001), and higher Charlson comorbidity index (CCI) (aOR 1.18, 95% CI 1.04-1.34; p = .010). In epilepsy, admissions between August and December 2020 or January and May 2021 were associated with a lower odds of non-routine discharge and decreased LOS compared to admissions between March and July 2020, but this difference was not statistically significant. SIGNIFICANCE: People with COVID-19 who had epilepsy had a higher odds of non-routine discharge and longer LOS but not higher mortality. Older age (≥65), ventilator use, and higher CCI were associated with COVID-19 mortality in epilepsy. This suggests that older adults with epilepsy and multimorbidity are more vulnerable than those without and should be monitored closely in the setting of COVID-19.

A Good Farewell? Positive Exits from Federal Housing Assistance and Lower Acute Healthcare Utilization.

Little is known regarding the health outcomes of people who exit from housing assistance and if that experience varies by the circumstances under which a person exits. We asked two questions: (1) does the type of exit from housing assistance matter for healthcare utilization? And (2) how does each exit type compare to remaining in housing assistance in terms of healthcare utilization? This retrospective cohort study of 5550 exits between 2012 and 2018 used data from two large, urban public housing authorities in King County, Washington. Exposures were exiting from housing assistance and type of exit (positive, neutral, negative). Outcomes were emergency department visits, hospitalizations, and well-child checks (among those aged < 6) in the year following exit from housing assistance. After adjustment for demographics and baseline healthcare utilization, people with positive exits had 26% (95% confident interval: 6-39%) lower odds of having 1 + ED visits in the year following exit than people with negative exits and 20% (95% CI: 6-31%) lower odds than those who continued receiving housing assistance. Neutral and negative exits did not differ substantially from each other, and both exit types appear to be detrimental to health, with higher levels of ED visits and hospitalizations and lower levels of well-child checks. Why people exit from housing assistance matters. Those with negative exits experience poorer outcomes and efforts should be made to both prevent this kind of exit and mitigate its impact.

Planarian EGF repeat-containing genes megf6 and hemicentin are required to restrict the stem cell compartment.

The extracellular matrix (ECM) is important for maintaining the boundaries between tissues. This role is particularly critical in the stem cell niche, as pre-neoplastic or cancerous stem cells must pass these boundaries in order to invade into the surrounding tissue. Here, we examine the role of the ECM as a regulator of the stem cell compartment in the planarian Schmidtea mediterranea, a highly regenerative, long-lived organism with a large population of adult stem cells. We identify two EGF repeat-containing genes, megf6 and hemicentin, with identical knockdown phenotypes. We find that megf6 and hemicentin are needed to maintain the structure of the basal lamina, and in the absence of either gene, pluripotent stem cells migrate ectopically outside of their compartment and hyper-proliferate, causing lesions in the body wall muscle. These muscle lesions and ectopic stem cells are also associated with ectopic gut branches, which protrude from the normal gut towards the dorsal side of the animal. Interestingly, both megf6 and hemicentin knockdown worms are capable of regenerating tissue free of both muscle lesions and ectopic cells, indicating that these genes are dispensable for regeneration. These results provide insight into the role of planarian ECM in restricting the stem cell compartment, and suggest that signals within the compartment may act to suppress stem cell hyperproliferation.

Predictors of chronic pain and disability in patients treated conservatively after distal radius fracture: a prospective cohort study.

PURPOSE: To determine predictors of chronic pain and disability among patients with distal radius fractures (DRF) treated conservatively with closed reduction and cast immobilization. METHODS: This was a prospective cohort study. Information on patient characteristics, post-reduction radiographic parameters, finger and wrist range of motion, psychological status (Hospital Anxiety and Depression Scale or HADS), pain (Numeric Rating Scale or NRS), and self-perceived disability (Disabilities of the Arm, Should, and Hand or DASH) were taken at baseline, cast removal, and 24 weeks. Differences in outcomes between time points were determined using analysis of variance. Multiple linear regressions were used to determine predictors of pain and disability at 24 weeks. RESULTS: One hundred forty patients with DRF (70% women, age: 67.0 ± 17.9) completed 24 weeks of follow-up and were included in the analysis. NRS (off-cast), range of ulnar deviation (off-cast), and greater occupational demands were significant predictors of pain at week 24 (adjusted R2 = 0.331, p < 0.001). Significant predictors of perceived disability at week 24 were HADS (off cast), sex (female), dominant-hand injury, and range of ulnar deviation (off cast) (adjusted R2 = 0.265, p < 0.001). CONCLUSIONS: Off-cast NRS and HADS scores are important modifiable predictors of patient-reported pain and disability at 24 weeks in patients with DRF. These factors should be targeted in the prevention of chronic pain and disability post-DRF.

The surveillance of spike protein for patients with COVID-19 detected in Hong Kong in 2020.

In 2020, numerous fast-spreading severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have been reported. These variants had unusually high genetic changes in the spike (S) protein. In an attempt to understand the genetic background of SARS-CoV-2 viruses in Hong Kong, especially before vaccination, the purpose of this study is to summarize the S protein mutations detected among coronavirus disease 2019 (COVID-19) patients in Hong Kong in 2020. COVID-19 cases were selected every month in 2020. One virus from each case was analyzed. The full encoding region of the S proteins was sequenced. From January 2020 to December 2020, a total of 340 COVID-19 viruses were sequenced. The amino acids of the S protein for 44 (12.9%) were identical to the reference sequence, WIV04 (GenBank accession MN996528). For the remaining 296 sequences (87.1%), a total of 43 nonsynonymous substitution patterns were found. Of the nonsynonymous substitutions found, some of them were only detected at specific time intervals and then they disappeared. The ongoing genetic surveillance system is important. It would facilitate early detection of mutations that can increase infectivity as well as mutations that are selected for the virus to escape immunological restraint.

Seasonal fluxes and sources apportionment of dissolved inorganic nitrogen wet deposition at different land-use sites in the Three Gorges reservoir area.

To identify seasonal fluxes and sources of dissolved inorganic nitrogen (DIN) wet deposition, concentrations and δ15N signatures of nitrate (NO3-) and ammonium (NH4+) in wet precipitation were measured at four typical land-use types in the Three Gorges reservoir (TGR) area of southwest China for a one-year period. Higher DIN fluxes were recorded in spring and summer and their total fluxes (averaged 7.58 kg N ha-1) were similar to the critical loads in aquatic ecosystems. Significant differences of precipitation δ15N were observed for NH4+-N between town and wetland sites in spring and between urban and rural sites in summer. For NO3--N, significant differences of precipitation δ15N were observed between town and rural sites in spring and between urban and town sites in autumn, respectively. Quantitative results of NO3--N sources showed that both biomass burning and coal combustion had higher fluxes at the urban site especially in winter (0.18 ± 0.09 and 0.19 ± 0.08 kg N ha-1), which were about three times higher than those at the town site. A similar finding was observed for soil emission and vehicle exhausts in winter. On the whole, DIN wet deposition averaged at 12.13 kg N ha-1 yr-1 with the urban site as the hotspot (17.50 kg N ha-1 yr-1) and regional NO3--N fluxes had a seasonal pattern with minimum values in winter. The contribution to NO3--N wet deposition from biomass burning was 26.1 ± 14.1%, which is the second dominant factor lower than coal combustion (26.5 ± 12.6%) in the TGR area during spring and summer. Hence N emission reduction from biomass burning, coal combustion and vehicle exhausts should be strengthened especially in spring and summer to effectively manage DIN pollution for the sustainable development in TGR area.

Effects of Soil Amendments on Microbial Activities in a Typical Cd-Contaminated Purple Field Soil, Southwestern China.

In this study, three soil amendments (inorganic, liming, or organic-inorganic materials) were used in a Cd-contaminated purple field soil to investigate their impacts on soil Cd availability, enzyme (urease, catalase, sucrase, and acid phosphatase) activities, microbial biomass (carbon/nitrogen) and type (bacteria, fungi, and actinomycetes) in mustard and corn trials. Results showed that soil amendments generally decreased soil exchangeable Cd, fungi and bacterial populations while increasing the activities of all the four soil enzymes tested, microbial biomass carbon and populations of actinomycetes (p < 0.05). Soil pH and microbial biomass nitrogen did not exhibit any significant response (p > 0.05) whereas stronger effects appeared in soil organic matter and available nutrients (nitrogen, phosphorous and potassium; p < 0.05). However, only soil available phosphorous significantly correlated with soil microbial activity in both mustard and corn trails (p < 0.05). Thus, application of phosphorous-containing amendments should be considered for promoting soil health in the remediation of the Cd-contaminated purple soils.

Pre-operative intravenous steroid improves pain and joint mobility after total knee arthroplasty in Chinese population: a double-blind randomized controlled trial.

INTRODUCTION: This study aims to investigate the effect of pre-operative intravenous methylprednisolone on post-operative pain control and joint mobility in Chinese patients undergoing single primary total knee arthroplasty. METHODS: This is a prospective, randomized, double-blinded, placebo-controlled single-centre trial. Sixty subjects were randomized into intervention and control group. The peri-operative anaesthetic and analgesic regimes were standardized. The intervention group received 125 mg methylprednisolone intravenously on the induction of anaesthesia. Subjects were assessed at 24, 30 and 48 h after surgery and upon discharge for pain scores and range of movement from the operated knee. Change in C-reactive protein level was calculated. Patient's satisfaction was recorded. Adverse reactions were documented. Subjects were followed up at 6 weeks, 4 months and 1 year. RESULTS: Rest pain and pain on movement were significantly reduced in the methylprednisolone group at 24 and 30 h after surgery (ANOVA p = 0.030, p = 0.003, p = 0.032, p = 0.010). The methylprednisolone group demonstrated a greater range of movement from the operated knee up to 30 h after surgery (ANOVA p = 0.031). Post-operative C-reactive protein level was significantly less in the methylprednisolone group (p < 0.001). Methylprednisolone group had a higher patient's satisfaction than the control group (p < 0.01). No adverse effects were noted at the 1-year follow-up. CONCLUSION: Pre-operative intravenous methylprednisolone improves post-operative pain and joint mobility after total knee arthroplasty up to 30 h after operation. It results in a higher patients' satisfaction. It can act as an effective adjunct in the multimodal analgesic regime. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03082092.

Symptoms of posttraumatic stress disorder among hospitalized patients with cancer.

BACKGROUND: Patients with cancer experience many stressors placing them at risk for posttraumatic stress disorder (PTSD) symptoms, yet little is known about factors associated with PTSD symptoms in this population. This study explored relationships among patients' PTSD symptoms, physical and psychological symptom burden, and risk for hospital readmissions. METHODS: We prospectively enrolled patients with cancer admitted for an unplanned hospitalization from August 2015-April 2017. Upon admission, we assessed patients' PTSD symptoms (Primary Care PTSD Screen), as well as physical (Edmonton Symptom Assessment System [ESAS]) and psychological (Patient Health Questionnaire 4 [PHQ-4]) symptoms. We examined associations between PTSD symptoms and patients' physical and psychological symptom burden using linear regression. We evaluated relationships between PTSD symptoms and unplanned hospital readmissions within 90-days using Cox regression. RESULTS: We enrolled 954 of 1,087 (87.8%) patients approached, and 127 (13.3%) screened positive for PTSD symptoms. The 90-day hospital readmission rate was 38.9%. Younger age, female sex, greater comorbidities, and genitourinary cancer type were associated with higher PTSD scores. Patients' PTSD symptoms were associated with physical symptoms (ESAS physical: B = 3.41; P < .001), the total symptom burden (ESAS total: B = 5.97; P < .001), depression (PHQ-4 depression: B = 0.67; P < .001), and anxiety symptoms (PHQ-4 anxiety: B = 0.71; P < .001). Patients' PTSD symptoms were associated with a lower risk of hospital readmissions (hazard ratio, 0.81; P = .001). CONCLUSIONS: A high proportion of hospitalized patients with cancer experience PTSD symptoms, which are associated with a greater physical and psychological symptom burden and a lower risk of hospital readmissions. Interventions to address patients' PTSD symptoms are needed and should account for their physical and psychological symptom burden. Cancer 2018. © 2018 American Cancer Society.

Contrast-Enhanced Ultrasound of the Liver: Optimizing Technique and Clinical Applications.

OBJECTIVE: The purpose of this article is to review the general principles, technique, and clinical applications of contrast-enhanced ultrasound of the liver. CONCLUSION: Proper technique and optimization of contrast-enhanced ultrasound require a balance between maintaining the integrity of the microbubble contrast agent and preserving the ultrasound signal. Established and emerging applications in the liver include diagnosis of focal lesions, aiding ultrasound-guided intervention, monitoring of therapy, and aiding surgical management.

An Integrated Source Apportionment Methodology and Its Application over the Yangtze River Delta Region, China.

An integrated source apportionment methodology is developed by amalgamating the receptor-oriented model (ROM) and source-oriented numerical simulations (SOM) together to eliminate the weaknesses of individual SA methods. This approach attempts to apportion and dissect the PM2.5 sources in the Yangtze River Delta region during winter. First, three ROM models (CMB, PMF, ME2) are applied and compared for the preliminary SA results, with information from PM2.5 sampling and lab analysis during the winter seasons. The detailed source category contribution of SOM to PM2.5 is further simulated using the WRF-CAMx model. The two pieces of information from both ROM and SOM are then stitched together to give a comprehensive information on the PM2.5 sources over the region. With the integrated approach, the detailed contributing sources of the ambient PM2.5 at different receptors including rural and urban, coastal and in-land, northern and southern receptors are analyzed. The results are compared with previous data and shows good agreement. This integrative approach is more comprehensive and is able to produce a more profound and detailed understanding between the sources and receptors, compared with single models.

Direct regulation of GAS6/AXL signaling by HIF promotes renal metastasis through SRC and MET.

Dysregulation of the von Hippel-Lindau/hypoxia-inducible transcription factor (HIF) signaling pathway promotes clear cell renal cell carcinoma (ccRCC) progression and metastasis. The protein kinase GAS6/AXL signaling pathway has recently been implicated as an essential mediator of metastasis and receptor tyrosine kinase crosstalk in cancer. Here we establish a molecular link between HIF stabilization and induction of AXL receptor expression in metastatic ccRCC. We found that HIF-1 and HIF-2 directly activate the expression of AXL by binding to the hypoxia-response element in the AXL proximal promoter. Importantly, genetic and therapeutic inactivation of AXL signaling in metastatic ccRCC cells reversed the invasive and metastatic phenotype in vivo. Furthermore, we define a pathway by which GAS6/AXL signaling uses lateral activation of the met proto-oncogene (MET) through SRC proto-oncogene nonreceptor tyrosine kinase to maximize cellular invasion. Clinically, AXL expression in primary tumors of ccRCC patients correlates with aggressive tumor behavior and patient lethality. These findings provide an alternative model for SRC and MET activation by growth arrest-specific 6 in ccRCC and identify AXL as a therapeutic target driving the aggressive phenotype in renal clear cell carcinoma.

Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans.

Immunomodulators have been shown to improve the outcome of severe pneumonia. We have previously shown that mycophenolic acid (MPA), an immunomodulator, has antiviral activity against influenza A/WSN/1933(H1N1) using a high-throughput chemical screening assay. This study further investigated the antiviral activity and mechanism of action of MPA against contemporary clinical isolates of influenza A and B viruses. The 50 % cellular cytotoxicity (CC50) of MPA in Madin Darby canine kidney cell line was over 50 µM. MPA prevented influenza virus-induced cell death in the cell-protection assay, with significantly lower IC50 for influenza B virus B/411 than that of influenza A(H1N1)pdm09 virus H1/415 (0.208 vs 1.510 µM, P=0.0001). For H1/415, MPA interfered with the early stage of viral replication before protein synthesis. For B/411, MPA may also act at a later stage since MPA was active against B/411 even when added 12 h post-infection. Virus-yield reduction assay showed that the replication of B/411 was completely inhibited by MPA at concentrations ≥0.78 µM, while there was a dose-dependent reduction of viral titer for H1/415. The antiviral effect of MPA was completely reverted by guanosine supplementation. Plaque reduction assay showed that MPA had antiviral activity against eight different clinical isolates of A(H1N1), A(H3N2), A(H7N9) and influenza B viruses (IC50 <1 µM). In summary, MPA has broad-spectrum antiviral activity against human and avian-origin influenza viruses, in addition to its immunomodulatory activity. Together with a high chemotherapeutic index, the use of MPA as an antiviral agent should be further investigated in vivo.

Recombinant influenza A virus hemagglutinin HA2 subunit protects mice against influenza A(H7N9) virus infection.

A novel avian influenza A(H7N9) virus has emerged to infect humans in eastern China since 2013. An effective vaccine is needed because of the high mortality despite antiviral treatment and intensive care. We sought to develop an effective vaccine for A(H7N9) virus. The HA2 subunit was chosen as the vaccine antigen because it is highly conserved among the human A(H7N9) virus strains. Moreover, in silico analysis predicted two immunogenic regions within the HA2 subunit that may contain potential human B-cell epitopes. The HA2 fragment was readily expressed in Escherichia coli. In BALB/c mice, intraperitoneal immunization with two doses of HA2 with imiquimod (2-dose-imiquimod) elicited the highest geometric mean titer (GMT) of anti-HA2 IgG (12699), which was greater than that of two doses of HA2 without imiquimod (2-dose-no-adjuvant) (6350), one dose of HA2 with imiquimod (1-dose-imiquimod) (2000) and one dose of HA2 without imiquimod (1-dose-no-adjuvant) (794). The titer of anti-HA2 IgG was significantly higher in the 1-dose-imiquimod group than the 1-dose-no-adjuvant group. Although both hemagglutination inhibition titers and microneutralization titers were below 10, serum from immunized mice showed neutralizing activity in a fluorescent focus microneutralization assay. In a viral challenge experiment, the 2-dose-imiquimod group had the best survival rate (100 %), followed by the 2-dose-no-adjuvant group (90 %), the 1-dose-imiquimod group (70 %) and the 1-dose-no-adjuvant group (40 %). The 2-dose-imiquimod group also had significantly lower mean pulmonary viral loads than the 1-dose-imiquimod, 1-dose-no-adjuvant and non-immunized groups. This recombinant A(H7N9)-HA2 vaccine should be investigated as a complement to egg- or cell-based live attenuated or subunit influenza vaccines.

The Role of Contrast-enhanced Ultrasound in Guiding Radiofrequency Ablation of Hepatocellular Carcinoma: A Retrospective Study.

PURPOSE: The objective of the study was to determine the efficacy of contrast-enhanced ultrasound (CEUS) using ultrasound (US)-specific microbubbles in guiding radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). METHODS: A retrospective analysis of 50 patients with HCC treated with CEUS guided RFA using perflutren at our institution was performed. CEUS images were first compared to B-mode US images performed at the same RFA session to determine the ability of CEUS to increase the conspicuity of lesions. A qualitative score (1 = poor, 2 = fair, 3 = excellent) was used to grade the ability to visualize the lesions. The preprocedure CEUS images were then evaluated using the most recent prior contrast enhanced computed tomography (CT) or magnetic resonance imaging (MRI). The efficacy of the treatment was evaluated with short-term follow-up imaging (median 1 month) for presence of residual or recurrent disease. RESULTS: CEUS allows at least fair visualization (score ≥2) in 78% (reader 1) and 80% (reader 2) of the lesions not visualized by B-mode US, and 50% (reader 1) and 42% (reader 2) of the lesions poorly visualized by B-mode US. Lesion appearances on CEUS are largely concordant with those on CT or MRI: 88% for reader 1, 96% for reader 2. With CEUS-guided RFA, complete response was achieved in the vast majority of the lesions at short-term follow-up: 82% for reader 1, 94% for reader 2. CONCLUSIONS: CEUS increases the conspicuity and provides better characterization of hypervascular HCC that are either not seen or poorly seen on B-mode US, and CEUS provides real-time guidance of RFA with good short-term treatment responses.

Neuropsychiatric complications of coronavirus disease 2019: Mount Sinai Health System cohort study.

OBJECTIVE: To describe the frequency of neuropsychiatric complications among hospitalized patients with coronavirus disease 2019 (COVID-19) and their association with pre-existing comorbidities and clinical outcomes. METHODS: We retrospectively identified all patients hospitalized with COVID-19 within a large multicenter New York City health system between March 15, 2020 and May 17, 2021 and randomly selected a representative cohort for detailed chart review. Clinical data, including the occurrence of neuropsychiatric complications (categorized as either altered mental status [AMS] or other neuropsychiatric complications) and in-hospital mortality, were extracted using an electronic medical record database and individual chart review. Associations between neuropsychiatric complications, comorbidities, laboratory findings, and in-hospital mortality were assessed using multivariate logistic regression. RESULTS: Our study cohort consisted of 974 patients, the majority were admitted during the first wave of the pandemic. Patients were treated with anticoagulation (88.4%), glucocorticoids (24.8%), and remdesivir (10.5%); 18.6% experienced severe COVID-19 pneumonia (evidenced by ventilator requirement). Neuropsychiatric complications occurred in 58.8% of patients; 39.8% experienced AMS; and 19.0% experienced at least one other complication (seizures in 1.4%, ischemic stroke in 1.6%, hemorrhagic stroke in 1.0%) or symptom (headache in 11.4%, anxiety in 6.8%, ataxia in 6.3%). Higher odds of mortality, which occurred in 22.0%, were associated with AMS, ventilator support, increasing age, and higher serum inflammatory marker levels. Anticoagulant therapy was associated with lower odds of mortality and AMS. CONCLUSION: Neuropsychiatric complications of COVID-19, especially AMS, were common, varied, and associated with in-hospital mortality in a diverse multicenter cohort at an epicenter of the COVID-19 pandemic.

Synthesis of a new biocomposite for fertiliser coating: assessment of biodegradability and thermal stability.

The bio- and thermal degradation as well as the water absorption properties of a novel biocomposite comprising cellulose nanoparticles, natural rubber and polylactic acid have been investigated. The biodegradation process was studied through an assembled condition based on the soil collected from the central Malaysian palm oil forests located in the University of Nottingham Malaysia. The effects of the presence of the cellulose nanoparticles and natural rubber on the biodegradation of polylactic acid were investigated. The biodegradation process was studied via thermal gravimetric analysis and scanning electron microscopy. It was understood that the reinforcement of polylactic acid with cellulose nanoparticles and natural rubber increases the thermal stability by ~ 20 °C. Limited amorphous regions on the surface of the cellulose nanoparticles accelerated the biodegradation and water absorption processes. Based on the obtained results, it is predicted that complete biodegradation of the synthesised biocomposites can take place in 3062 h, highlighting promising agricultural applications for this biocomposite.