Identification of human T cell receptor gammadelta-recognized epitopes/proteins via CDR3delta peptide-based immunobiochemical strategy.
Human T lymphocytes, bearing T cell receptor (TCR) gammadelta, play an important role in anti-tumor/microbe immune responses. However, few tumor antigens recognized by TCRgammadelta have been defined so far. To investigate antigenic epitopes/proteins recognized by gammadeltaT cells, we have established a new immunobiochemical strategy that uses complementarity-determining region 3 of TCR delta chain (CDR3delta) peptide-mediated epitope/protein-binding assays. CDR3delta peptides synthesized using the CDR3 region in TCR Vdelta2 chain were validated for their binding specificity to target cells or tissues. These CDR3delta peptides were then employed as probes to pan putative epitopes in a 12-mer random peptide phage-displayed library and to identify putative protein ligands within tumor protein extracts by affinity chromatography and liquid chromatography/electrospray ionization-tandem mass spectrometry analysis. As a result, we have identified nine peptides and two proteins for TCRgammadelta, including human mutS homolog 2 (hMSH2) and heat shock protein (HSP) 60. All nine tested epitope peptides not only bind to gammadeltaT cells but also functionally activate gammadeltaT cells in vitro. Identification of HSP60 confirms the validity of this method as HSP60 is an identified ligand for TCRgammadelta. We show that hMSH2 is expressed on the surface of SKOV3 tumor cells, and cytotoxicity of Vdelta2 gammadeltaT cells to SKOV3 cells was blocked by anti-hMSH2 antibody, suggesting that hMSH2 may be a new ligand for TCRgammadelta. Taken together, our findings provide a novel immunobiochemical strategy to identify epitopes/proteins recognized by gammadeltaT cells.


Population regulation of the native holly leafminer, Phytomyza ilicicola Loew (Diptera: Agromyzidae), on American holly.
Three sources of mortality, intraspecific competition, parasitism, and early leaf abscission, were investigated to determine their importance in regulating populations of the leafminer Phytomyza ilicicola Loew (Diptera: Agromyzidae) on cultivated American holly trees. Spatial aggregation of leafminers among leaves resulted in density-dependent mortality from interference and from intraspecific competition for nutritional resources. Pupal weight of survivors decreased significantly as within-leaf density increased. Within-tree parasitism of P. ilicicola by Opius striativentris (Hymenoptera: Braconidae) ranged from 3%-58%, but parasitism was independent of host density both for individual leaves and on a tree-wide spatial scale. The incidence of early leaf abscission was significantly higher for mined than for unmined leaves, with about 14% of the mined leaves abscising before the adult leafminers emerged. There was high mortality of both P. ilicicola and O. striativentris within fallen leaves. These results are discussed in relation to recent hypotheses concerning the role of competition, parasitism, and early leaf abscission in population regulation of leafminers.


Antioxidative role of palm grass rhizome ameliorates anxiety and depression in experimental rodents and computer-aided model.
Palm grass (Curculigo recurvata) is an ethnomedicinally important herb reported to have significant medicinal values. The present study aimed to evaluate the antidepressant and anxiolytic activities of a methanol extract of C. recurvata rhizome (Me-RCR) through different approaches. The antidepressant and anxiolytic properties of Me-RCR were assessed by using elevated plus maze (EPM), hole-board (HBT), tail suspension (TST), and forced swimming (FST) tests in Swiss Albino mice. The in-depth antioxidative potential of Me-RCR was also evaluated through DPPH radical scavenging activity, ferric-reducing power capacity, total phenolic, flavonoid, flavonol, and antioxidant content analysis. Computational investigations were performed using computer-aided methods for screening the anxiolytic, antidepressant, and antioxidative activities of the selected lead molecules. Treatment with Me-RCR (200 and 400 mg/kg, b.w.) notably increased the number of open arm entries and the time spent in the EPM test. In the HBT, Me-RCR exhibited significant anxiolytic activity at a dose of 200 mg/kg, whereas similar activity was observed at 400 mg/kg in the EPM test. Me-RCR significantly decreased the immobility time in a dose-dependent manner in both TST and FST. The IC50 for DPPH and reducing power capacity assay were found to be 18.56 and 193 μg/mL, respectively. Promising outcomes were noted for the determination of total phenolics, flavonoids, flavonols, and antioxidant capacity. In the case of computer-aided studies, nyasicoside showed promising binding energy for antidepressant and anxiolytic activities, whereas isocurculigine demonstrated promising effects as an antioxidant. Overall, these findings suggest that Me-RCR could be a favourable therapeutic candidate for the treatment of mental and psychiatric disorders, as well as a good source of antioxidants.


Exposure to an extreme environment comes at a sensorimotor cost.
Long duration space flight is known to induce severe modifications in the sensorimotor and musculoskeletal systems. While in-flight strategies including physical fitness have been used to prevent the loss of bone and muscle mass using appropriate rehabilitative countermeasures, less attention has been put forth in the design of technologies that can quickly and effectively assess sensorimotor function during missions in space. The aims of the present study were therefore (1) to develop a Portable Sensorimotor Assessment Platform (PSAP) to enable a crewmember to independently and quickly assess his/her sensorimotor function during the NASA's Extreme Environment Mission Operations (NEEMO) and (2) to investigate changes in performance of static posture, tandem gait, and lower limb ataxia due to exposure in an extreme environment. Our data reveal that measuring the degree of upper body balance and gait regularity during tandem walking using PSAP provided a sensitive and objective quantification of body movement abnormalities due to changes in sensorimotor performance over the duration of mission exposure.


Unraveling the Structure-Dependent Inhibitory Effects of Ginsenoside Series Compounds on Human Cytochrome P450 1B1.
Cytochrome P450 1B1(CYP1B1) is an extrahepatic P450 isoenzyme that can participate in processes of undermining the effectiveness and safety of anti-cancer therapy. Ginsenosides are the main active ingredients in ginseng, which possesses rich pharmacological activities, including anti-cancer activity and organ protection. However, the effect of ginsenosides on the activity of CYP1B1 remains unclear. The present study aimed to investigate the inhibitory effect of ginsenosides on CYP1B1 and reveal the structure-inhibitory activity relationship. Firstly, recombinant CYP1B1 and EROD reactions were used to evaluate the inhibitory effect of ginsenosides. Secondly, molecular docking was used to simulate the interactions between ginsenosides and CYP1B1. Finally, the structure-inhibitory activity relationship was analyzed. The ginsenosides, Rb2, Rd, and Rg3, significantly inhibited CYP1B1; the ginsenoside Rd showed the strongest inhibition effect, with a Ki value of 47.37 μM in non-competitive mode. Notably, ginsenoside Rd formed hydrogen bonds with two key amino acid residues of CYP1B1, and one bond was between the glycosyl in position 20 and ALA330, which also made ginsenoside Rd close to the heme iron of CYP1B1. In contrast, ginsenosides, Rb2 and Rg3, which showed weaker inhibition, interacted with only one CYP1B1 residue by the hydrogen bond, which was far away from the heme iron. Finally, the structure-inhibitory activity relationship analysis demonstrated that the number of glycosyls in position 20 and the type of sapogenins in the ginsenoside structure are the key factors determining inhibitory activity. Meanwhile, ALA330 was a vital amino acid in the potent inhibition of CYP1B1 by ginsenosides. A structure-dependent inhibitory effect on CYP1B1 was revealed for ginsenosides, among which ginsenoside Rd showed the strongest inhibition due to its mono-glycosyl in position 20 of the ginsenoside parent structure. These findings would provide evidence for the synthesis of novel CYP1B1 inhibitors to augment the anti-cancer therapeutic effect.


Transport and retention of polymeric and other engineered nanoparticles in porous media.
Increasing applications of nanoparticles (NPs) in agriculture have raised potential risks to soil and aquatic ecosystems. A comparative study examining the transport of commonly used NPs in porous media is of critical significance for their application and regulation in agroecosystems. In this study, laboratory column leaching experiments were conducted to investigate the transport and retention of polysuccinimide NPs (PSI-NPs) in two saturated porous media with different grain sizes, as compared with multi-walled carbon nanotubes (MWCNTs), nano-Ag and nano-TiO2. Zeta potential of the NPs was negative at pH6.3 and decreased in an order of PSI-NPs > nano-TiO2 > MWCNTs > nano-Ag. The coarse and fine sands used in this study had negative charges with similar zeta potentials. The movement of NPs was affected by grain size, with larger sizes facilitating mobility while finer sizes favoring retention of NPs in the porous matrix. The retention profile significantly varied between the two sand columns, with more NPs transported to deeper layers in the coarse sand than the fine sand. The relative percentage of NPs detected in leachate was found to be positively correlated with the zeta potential of NPs (r = 0.931). Among the NPs, nano-Ag had the most negative zeta potential, and therefore was the most mobile, followed by MWCNTs and nano-TiO2. Having the least negative zeta potential, PSI-NPs had the lowest mobility, as compared with other NPs regardless of matrix grain size. This work reveals grain size and zeta potential of NPs are major factors that influence transport of NPs along the vertical porous profile, as well as demonstrating the relative unimportance of NP composition, which could serve as important guideline in nanomaterials application, risk assessment, and waste management in agroecosystems.


Retracted: Design and Optimization of Aesthetic Education Teaching Information Platform Based on Big Data Analysis.
[This retracts the article DOI: 10.1155/2022/5109638.].


[Differential diagnosis of parkinsonian syndromes using MRI].
The differential diagnosis of parkinsonian syndromes is considered one of the most challenging in clinical neurology. Despite published consensus operational criteria for the diagnosis of Parkinson's disease (PD) and the various atypical parkinsonian disorders (APD), such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal degeneration (CBD), the clinical separation of APDs from PD carries a high rate of misdiagnosis. However, the early differentiation between APD and PD, each characterized by a very different natural history, is crucial for determining the prognosis and choosing a treatment strategy. Despite limitations the various modern magnetic resonance imaging (MRI) techniques have undoubtedly added to the differential diagnosis of neurodegenerative parkinsonism. In clinical practice conventional MRI with visual assessment of T2 and T1-weighted imaging is a well established method for the exclusion of symptomatic parkinsonism due to other pathologies and may also point to the diagnosis of APD. Furthermore, advances in MRI techniques, such as diffusion-weighted imaging (DWI), have enabled abnormalities in the basal ganglia and infratentorial brain structures in APD to be quantitatively illustrated.


Hand-assisted laparoscopic and thoracoscopic surgery (HALTS) in radical esophagectomy with three-field lymphadenectomy for thoracic esophageal cancer.
To prove the feasibility of hand-assisted laparoscopic and thoracoscopic surgery (HALTS) for radical esophagectomy with three-field lymphadenectomy to thoracic esophageal cancer. Esophagectomy with three-field lymphadenectomy was performed using HALTS in 19 patients with thoracic esophageal cancer without distant metastasis. Five patients had chemo-radiotherapy prior to surgery. All operations were completed successfully without the need for open surgery. Mean surgical time was 476+/-58 min, and mean blood loss during surgery was 343+/-184 mL. All patients started tube feeding and were moved from the intensive care unit to the general surgery ward the day after surgery. Discharge occurred a median of 10 days after surgery. Fifteen patients could return to full time jobs from 8 to 62 days after surgery (median 22 days) and from 1 to 35 days after discharge (median 9 days). Other three could return to daily activities at home soon as well. No major complications occurred, except one anastomotic leak. In terms of lung function, %FEV(1) was not changed whereas %VC was reduced significantly 1 month after surgery. All but two recurrences have been healthy without a relapse for a mean of 289 days. These results suggest that HALTS may be a useful surgical technique to reduce the invasiveness of conventional radical esophagectomy with three-field lymphadenectomy for thoracic esophageal cancer.


The v-Src and c-Src tyrosine kinases immunoprecipitated from Rous sarcoma virus-transformed cells display different peptide substrate specificities.
In the cells transformed by Rous sarcoma virus (RSV), two Src proteins are expressed: the ubiquitous tyrosine kinase c-Src and the v-Src, the product of the transforming gene of the virus. Using three synthetic peptide substrates widely used for testing Src kinase activity, we show that they are phosphorylated with different efficiencies by the v-Src and c-Src tyrosine kinases immunoprecipitated from the tumor cell line H19. The v-Src displays higher efficiency (Vmax/Km ratio) toward all three peptides used, but the Vmax of v-Src is much lower than Vmax of c-Src with two peptides out of three. This difference in substrate specificity, if ignored, may cause misestimation of the amounts of active c-Src and v-Src in RSV-transformed cells. On the other hand, the different peptide substrate specificities may also reflect different protein substrate specificities of the v-Src and c-Src kinases in vivo.


Is positive school climate associated with better adolescent mental health? Longitudinal study of young people in England.
Studies suggest that individual student-reported connection to school is associated with better mental health. However, there is less evidence for associations between schools' overall school climate and the mental health of their students. This may reflect limitations in which mental health outcomes have been examined. We conducted a large longitudinal study in schools, hypothesising that we would find associations at both the student and school levels between student-reported positive school climate, and reduced student conduct and emotional problems and improved mental wellbeing. We tracked students in 20 English secondary schools from near the end of the first year of secondary school (age 11/12) over 3 years using reliable measures of school climate and mental health. We found associations between student-level reports of positive school climate at baseline, and reduced conduct and emotional problems and better mental wellbeing at 3-year follow-up adjusting for various potential confounders. We also found some evidence of adjusted associations between baseline school-level measures of overall positive climate and better student mental health at follow-up. However, these student- and school-level associations reduced considerably when also adjusting for baseline mental health. Our findings suggest that there are associations between school climate and student mental health at both the student and school level but these associations are complex and not necessarily causal.


Noninvasive echocardiographic cardiac power output predicts mortality in cardiac intensive care unit patients.
Low cardiac power output (CPO), measured invasively, can identify critically ill patients at increased risk of adverse outcomes, including mortality. We sought to determine whether non-invasive, echocardiographic CPO measurement was associated with mortality in cardiac intensive care unit (CICU) patients. Patients admitted to CICU between 2007 and 2018 with echocardiography performed within one day (before or after) admission and who had available data necessary for calculation of CPO were evaluated. Multivariable logistic regression determined the relationship between CPO and adjusted hospital mortality. A total of 5,585 patients (age of 68.3 ± 14.8 years, 36.7% female) were evaluated with admission diagnoses including acute coronary syndrome (ACS) in 56.7%, heart failure (HF) in 50.1%, cardiac arrest (CA) in 12.2%, shock in 15.5%, and cardiogenic shock (CS) in 12.8%. The mean left ventricular ejection fraction (LVEF) was 47.3 ± 16.2%, and the mean CPO was 1.04 ± 0.37 W. There were 419 in-hospital deaths (7.5%). CPO was inversely associated with the risk of hospital mortality, an association that was consistent among patients with ACS, HF, and CS. On multivariable analysis, higher CPO was associated with reduced hospital mortality (OR 0.960 per 0.1 W, 95CI 0.0.926-0.996, P = .03). Hospital mortality was particularly high in patients with low CPO coupled with reduced LVEF, increased vasopressor requirements, or higher admission lactate. Echocardiographic CPO was inversely associated with hospital mortality in unselected CICU patients, particularly among patients with increased lactate and vasopressor requirements. Routine calculation and reporting of CPO should be considered for echocardiograms performed in CICU patients.


Congenital mitral-aortic discontinuity.
Mitral-aortic (M-A) discontinuity is an uncommonly observed congenital malformation. From the embryologic point of view, it is a failure of the superior endocardial cushion of the A-V canal reach and insert into the aortic root (the mitral-aortic fibrous trigone). It should be differentiated from aorto-left ventricular discontinuity, a complication of endocarditis with excavating abscesses without boundaries. In congenital mitral-aortic discontinuity, the anterior leaflet of the mitral valve fails to insert into the aortic root. We report our experience with 2 patients. In patient 1, the severe left ventricular outflow obstruction was mainly caused by the mobile anterior leaflet of the mitral valve.


Low-flow cardiopulmonary bypass and cerebral protection: a summary of investigations.
A research program in cerebral ischemia was initiated by our laboratory to determine optimal strategies for cerebroprotection. Four studies relating to cerebroprotection using nuclear magnetic resonance spectroscopy in a sheep model of hypothermic cardiopulmonary bypass are summarized. These showed, first, that low-flow bypass, with a flow as low as 10 mL.kg-1 x min-1, maintained normal cerebral metabolism; second, that hypothermia increases the high-energy phosphate content and the intracellular pH of the brain; third, that hyperglycemia causes a profound intracellular acidosis; and, finally, that barbiturates prevent the normal increase in high-energy phosphates associated with hypothermia.


Partisanship and Covid-19 vaccination in the UK.
This article examines the association between partisanship and vaccination in the UK. The lower vaccination rates among Republicans in the US have been linked to ideology and President Trump's anti-vaccination rhetoric. By contrast, both ruling and opposition parties in the UK promoted the national vaccination program. Using two datasets at constituency and individual levels, we analyse whether there are partisan differences in uptake when vaccination garners cross-party support. Our findings contrast in important ways from the US case. First, the correlation between partisanship and vaccination is the opposite to that of the US: both Conservative constituencies and individuals are associated with higher vaccination rates than Labour across almost all age groups. Thus, right-leaning individuals do not necessarily vaccinate less, at least when their political party is in power and supportive of vaccination. Second, partisanship alone accounts for a large share of variation in vaccination rates, but this association appears largely driven by socio-economic and demographic differences: older and economically better off individuals and constituencies tend to be more vaccinated. Once these controls are included, the correlation between Conservative partisanship and vaccination shrinks substantially. Hence, the ideological source of the partisan gap in vaccination rates appears smaller than in the US.


Long-term follow-up of six patients with acute spinal injury following dural decompression.
We report six cases of spinal injury in which there was bony encroachment on the spinal cord. At the time of decompression the dura was noted to be tense and non-pulsatile. This method of anterior decompression of burst fractures of the spine suggests that bony decompression of the spinal canal associated with durotomy released the spinal epidural veins which had become congested and had inhibited the free flow of CSF, and we believe also had decreased arteriolar inflow to the cord. Full neurological recovery occurred in three of the six neurologically impaired patients and partial recovery in the remaining three. We believe that a dural decompression may be of some use in preventing a 'compartment syndrome' of the spinal cord. Further animal studies are recommended before the procedure is used routinely.


A new tumor imaging agent--111In-bleomycin complex. Comparison with 67Ga-citrate and 57Co-bleomycin in tumor-bearing animals.
We have found a new 111In-bleomycin complex (BLMC), which has high affinity to tumor, does not bind to transferrin and is stable in vivo. Distribution in animals bearing glioma, hepatoma, or mammary adenocarcinoma at 48 hours showed: the ratios of tumor to blood, brain, heart, lung, liver, pancreas, stomach, and femur were 1.4-22.4 times as high for 111In-BLMC as for 67Ga-citrate. In mammary adenocarcinoma, 111In-BLMC bound more to viable and 57Co-Bleomycin (BLM) more to necrotic tumor. In viable tumor, the concentration of 111In-BLMC was similar to that of 57Co-BLM. The ratios of tumor to stomach and pancreas were higher, to blood, brain, muscle, heart, and femur were lower for 111In-BLMC than those for 57Co-BLM. The ratios of tumor to lung, liver, spleen, skin, and kidney were similar for the two compounds. Tumors were imaged more distinctly with the new 111In-BLMC and 57Co-BLM than with 67Ga-citrate. 111In-BLMC is promising for tumor imaging.


Obesity Is Associated With High Perioperative Complications Among Surgically Treated Intertrochanteric Fracture of the Femur.
To document the complications among obese patients who underwent surgical fixation for intertrochanteric femur (IT) fractures and to compare with nonobese patients. Retrospective cohort study. Four level I trauma centers. 1078 IT fracture patients. None. Patient and fracture characteristics, surgical duration, surgical delay intraoperative and postoperative complications, inpatient mortality, and length of stay. A retrospective review at 4 academic level I trauma centers was conducted to identify skeletally mature patients who underwent surgical fixation of intertrochanteric fractures between June 2008 and December 2014. Descriptive data, injury characteristics, OTA fracture classification, and associated medical comorbidities were documented. The outcomes measured included in-hospital complications, length of stay, rate of blood transfusion, change in hemoglobin levels, operative time, and wound infection. Of 1078 unique patients who were treated for an IT fracture, 257 patients had a Body mass index (BMI) of 30 or greater. Patients with a high BMI (≥30) had a significantly lower mean age (73 vs. 77 years, P < 0.0001), higher percentage of high-energy injuries (18% vs. 9%, P = 0.0004), greater mean duration of surgery (96 vs. 86 minutes, P = 0.02), and higher mean length of stay (6.5 vs. 5.9 days, P = 0.004). The high-BMI group (n = 257) had significantly higher percentages of patients with complications overall (43% vs. 28%, P < 0.0001), respiratory complications (11% vs. 3%, P < 0.0001), electrolyte abnormalities (4% vs. 2%, P = 0.01), and sepsis (4% vs. 1%, P = 0.002). Patients with BMI ≥ 40 had a much higher rate of respiratory complications (18%) and wound complications (5%) than obese (BMI: 30-39.9) and nonobese patients (BMI < 30). Intertrochanteric hip fracture patients with a BMI of >30 kg/m are much more likely to sustain systemic complications including respiratory complications, electrolyte abnormalities, and sepsis. In addition, morbidly obese patients are more likely to sustain respiratory complications and wound infections than obese (BMI: 30-39.9 kg/m) and nonobese patients (BMI: < 30 kg/m). The findings from this study can help direct surgeons in the counseling to obese patients and their family, and perhaps increase hospital reimbursement for this group of patients. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Automatic retinoblastoma screening and surveillance using deep learning.
Retinoblastoma is the most common intraocular malignancy in childhood. With the advanced management strategy, the globe salvage and overall survival have significantly improved, which proposes subsequent challenges regarding long-term surveillance and offspring screening. This study aimed to apply a deep learning algorithm to reduce the burden of follow-up and offspring screening. This cohort study includes retinoblastoma patients who visited Beijing Tongren Hospital from March 2018 to January 2022 for deep learning algorism development. Clinical-suspected and treated retinoblastoma patients from February 2022 to June 2022 were prospectively collected for prospective validation. Images from the posterior pole and peripheral retina were collected, and reference standards were made according to the consensus of the multidisciplinary management team. A deep learning algorithm was trained to identify "normal fundus", "stable retinoblastoma" in which specific treatment is not required, and "active retinoblastoma" in which specific treatment is required. The performance of each classifier included sensitivity, specificity, accuracy, and cost-utility. A total of 36,623 images were included for developing the Deep Learning Assistant for Retinoblastoma Monitoring (DLA-RB) algorithm. In internal fivefold cross-validation, DLA-RB achieved an area under curve (AUC) of 0.998 (95% confidence interval [CI] 0.986-1.000) in distinguishing normal fundus and active retinoblastoma, and 0.940 (95% CI 0.851-0.996) in distinguishing stable and active retinoblastoma. From February 2022 to June 2022, 139 eyes of 103 patients were prospectively collected. In identifying active retinoblastoma tumours from all clinical-suspected patients and active retinoblastoma from all treated retinoblastoma patients, the AUC of DLA-RB reached 0.991 (95% CI 0.970-1.000), and 0.962 (95% CI 0.915-1.000), respectively. The combination between ophthalmologists and DLA-RB significantly improved the accuracy of competent ophthalmologists and residents regarding both binary tasks. Cost-utility analysis revealed DLA-RB-based diagnosis mode is cost-effective in both retinoblastoma diagnosis and active retinoblastoma identification. DLA-RB achieved high accuracy and sensitivity in identifying active retinoblastoma from the normal and stable retinoblastoma fundus. It can be used to surveil the activity of retinoblastoma during follow-up and screen high-risk offspring. Compared with referral procedures to ophthalmologic centres, DLA-RB-based screening and surveillance is cost-effective and can be incorporated within telemedicine programs. This study was registered on ClinicalTrials.gov (NCT05308043).


Double-echo three-point-Dixon method for fat suppression MRI.
A double-echo two-excitation pulse sequence encoding fat and water signals for a phase-sensitive three-point Dixon-type analysis (DE-3PD) was developed and implemented on a 1.5 T MR imager. Data processing was performed using a previously developed two-dimensional (2D) region-growing algorithm, adapted to use double-echo data. Density-, T1-, and T2-weighted fat suppression images were obtained from six volunteers using the new fat suppression method. The images were compared with corresponding images obtained using frequency-selective excitation fat suppression (FATSAT) and a single-echo three-point-Dixon method (SE-3PD). The results demonstrate that the DE-3PD sequence shortens the imaging time by one-third compared with the SE-3PD method, without loss in image quality. The data also show that a 2D region-growing algorithm effectively unwraps the phase of DE-3PD data sets, and that results of DE-3PD fat signal suppression are consistently better than those obtained using a standard FATSAT method. The authors conclude that the double-echo sequence provides density-, T1-, and T2-weighted images that appear to be promising for routine clinical applications.


Immunohistochemical Analysis Of Novel Biomarkers Cyclin D1, p53 And Ki67 In Endometrial Carcinoma: Clinicopathological Significance And Prognostic Value.
Endometrial carcinoma (EC) is the only gynecologic cancer with increasing incidence and mortality worldwide. This study aimed to determine association of cell proliferation marker CyclinD1, p53 and Ki67 with clinicopathological parameters and survival analysis in patients of EC. One hundred twenty-four histological confirmed cases of EC treated at our institute were included in this study. The appropriate tissue blocks of cases which were retrieved from 2010 to 2015. The study period was from Jan 2018 to Jan 2020. Data pertaining to patient's clinical details, histopathological diagnosis, treatment and follow up was retrieved from Hospital information System. Immunohistochemical evaluation of Cyclin D1, p53 and Ki67 was done. Overall survival and Disease-free survival for each category were analyzed by the Kaplan-Meier method. Of the 124 cases of EC, 108(87.09%) cases were of type I and 16 (12.89%) cases of type II. Overall positive staining of cyclinD1, p53 and Ki67 were noted in 53.22%, 42.22% and 32.3% cases respectively. The clinicopathological parameters affecting disease-free survival were age (p=0.039) histological types (p=0.007), and FIGO stage (p< 0.001). Elevated Ki67 index and p53 overexpression was associated with type II morphology (p= 0.001). Whereas Cyclin D1 expression was associated with type I morphology and poorly differentiated tumor. Cyclin D1 positive staining, p53overexpression and an elevated Ki-67index all had an independent prognostic significance in endometrial cancer. This panel of biomarkers may help to differentiate tumor behavior, and necessity for more radical surgery and post- operative chemotherapy. Key words: Endometrial carcinoma; cyclin D1; p53; Ki67; Survival analysis.


Antibodies to dehistonized chromatin of normal and fetal rat liver.
Antisera to dehistonized adult or fetal rat liver chromatin were treated with electrophoretically separated chromosomal proteins of adult and fetal liver, Novikoff hepatoma and adult rat kidney. Both types of antisera reacted with numerous antigens in both tissue chromatins. However, immunoabsorption experiments have shown that while adult rat liver shared most of its nuclear antigens with other tissues, antisera to dehistonized fetal liver chromatins were more specific. In terms of antigenic specificity, the fetal rat liver and Novikoff hepatoma chromatins were similar; however, the former contained several antigens which could not be absorbed with Novikoff hepatoma chromatin.


Predictive network modeling of single-phase non-Newtonian flow in porous media.
The majority of complex fluids used in oil-field applications are polymeric solutions exhibiting shear-thinning (pseudoplastic) behavior in solution. We study the flow of power-law fluids in porous media using network modeling. We use realistic representations of porous media that capture the geometry and topology of sands and sandstones as input to our flow model. The bulk rheology (variation of viscosity with shear rate) is used to define a relationship between pressure drop and average flow velocity in each pore. We then compute the variation of average velocity with apparent viscosity for the whole network. We successfully predict the results of four experiments from different sources in the literature. The predictions are superior to those using simplified capillary bundle models and involve no adjustable parameters, but are limited to polymer exhibiting simple shear-thinning behavior and require a detailed description of the pore space of interest.


Isolation and sequencing of a cDNA clone encoding acid phosphatase in rat liver lysosomes.
A full length cDNA for acid phosphatase in rat liver lysosomes was isolated and sequenced. The predicted amino acid sequence comprises 423 residues (48,332 Da). A putative signal peptide of 30 residues is followed by the NH2-terminal sequence of lysosomal acid phosphatase (45,096 Da). The deduced NH2-terminal 18-residue sequence is identical with that determined directly for acid phosphatases purified from the rat liver lysosomal membranes. The primary structure deduced for acid phosphatase contains 9 potential N-glycosylation sites and a hydrophobic region which could function as a transmembrane domain. It exhibits 89% and 67% sequence similarities in amino acids and nucleic acids, respectively, to human lysosomal acid phosphatase. The amino acid sequence of the putative transmembrane segment shows a complete similarity to that of the human enzyme. Northern blot hybridization analysis identified a single species of acid phosphatase mRNA (2.2 kbp in length) in rat liver.


Results of carotid angioplasty and stenting are equivalent for critical versus high-grade lesions in patients deemed high risk for carotid endarterectomy.
To examine outcomes of carotid angioplasty and stenting (CAS) in patients with critical carotid stenosis who are deemed high risk for carotid endarterectomy. Medical records were retrospectively analyzed for patients undergoing CAS between September 2002 and March 2011 at a single institution. Patients were classified as having either critical (≥ 90%) or high-grade (70%-89%) carotid stenosis based on angiography. The primary composite end point was stroke, myocardial infarction, or death from any cause during the periprocedural period or any ipsilateral stroke during the follow-up period. A total of 245 patients underwent 257 CAS procedures during the study period. Fifty-one percentage (n = 130) of cases involved critical stenosis (66.2% male; mean age, 71 ± 10 y), with the remaining group (n = 127) involving high-grade stenosis (67.7% male; mean age, 71 ± 9 y). Symptomatic carotid disease was present in 25% of the critical stenosis and 31% of the high-grade stenosis groups (P = 0.33). Chronic obstructive pulmonary disease was more commonly found in the high-grade stenosis group (20% versus 8%, P = 0.01). No difference was observed between the groups relative to other baseline demographic characteristics, presence of contralateral carotid occlusion, stent diameter or length, maximum balloon diameter or length, use of embolic protection device, or procedural duration. Technical success was achieved in all cases. There was no difference in the need to predilate before the introduction of the filter or stent based on the degree of stenosis. We found no difference in the primary composite end point between the high-grade or critical stenosis groups (7.1% versus 7.7%, P = 0.74), or there were no differences between the individual components of the composite end point. Mid-term survival was similar between the two groups at a mean follow-up period of 2.4 y. Despite concerns regarding the potential for increased neurologic complications, our data demonstrate that patients with high-grade and critical stenosis are able to safely undergo CAS and achieve similar periprocedural outcomes and mid-term prognosis.


diRNA-Ago2-RAD51 complexes at double-strand break sites.
The way in which the DNA damage response signals the presence of DNA lesions and mediates DNA repair has not been fully elucidated. Now, Gao et al. reveal that diRNA-Ago2 complexes recruit RAD51 to the break sites.


Effects of clinical dosage levels of methylphenidate on two-flash thresholds and perceptual motor performance in hyperactive children.
Three groups (ns = 10) of children (normals, hyperactives, hyperactives on medication) were administered eight perceptual-motor tasks. The normal controls were significantly superior in performance in comparison with the hyperactives taken off methylphenidate on three tasks but only superior on one task (Digit Symbol) when compared to hyperactives on methylphenidate. The hyperactives on medication were also significantly superior to the hyperactives not on medication on the Digit Symbol task.


The potential role of the implantable defibrillator in malignant ventricular arrhythmias.
A malignant arrhythmia is one which threatens life and is difficult to predict, prevent or treat. Any arrhythmia which falls into this category is an indication for the implantable defibrillator. The simplicity of this statement is of course deceiving. Transthoracic defibrillation, which for 20 years has been the therapeutic standard, has provided us with the greatest insight and understanding of cardiac arrhythmias. In the long run, the same information will be acquired with the implanted defibrillator. However, technical, medical and economic factors are more complex and will not be resolved in the near future.


The effect of transcranial direct current stimulation on cognitive performance in youth with persistent cognitive symptoms following concussion: a controlled pilot study.
Explore the feasibility, tolerability, and early efficacy of transcranial direct current stimulation (tDCS) as a therapeutic intervention for youth with cognitive persistent post-concussion symptoms (PPCS). tDCS improves performance on a dual task working memory (WM) paradigm in youth with cognitive PPCS. Twelve youth experiencing cognitive PPCS. A quasi-randomized pilot trial was used to explore the tolerability of, and performance differences on, a dual N-Back WM task paired with active or sham tDCS over 3 sessions. Accuracy and reaction time on WM task and self-report of tDCS tolerability. Trends toward increases in accuracy from Day 1 to 3 seen in both groups. Active tDCS group performed better than sham on Day 2 in N-Back level N2 (p = .019), and marginally better than the sham group on Day 3 in level N3 (p = .26). Participants reported tDCS as tolerable; compared to the active tDCS group, the sham group reported more "considerable" (p = .078) and "strong" symptoms (p = .097). tDCS is a promising tool for enhancing WM performance and is a feasible and tolerable adjunct to behavioral interventions in youth with cognitive PPCS. A clinical trial to demonstrate efficacy is warranted.


Measuring the Interaction of Sterols and Steroids with Proteins by Microscale Thermophoresis.
Determining the affinity and specificity of protein-lipid interactions is crucial for understanding the physiological function and mode of action of signaling lipids, including steroids. Here we describe a method that relies on microscale thermophoresis (MST) to monitor the binding of sterols and steroids to proteins. The protein of interest is expressed as a polyhistidine-tagged fusion in E. coli and purified by affinity chromatography on a nickel-based resin. The purified protein is then labeled with a fluorescent dye and incubated with a serial dilution of the lipid ligand. The protein-ligand interaction is monitored by MST, which detects the fraction of the protein bound to the ligand based on its altered mobility in a thermal gradient. A binding curve fitted to the measured data points is then used to calculate the corresponding dissociation constant.


Examining Correlates of Pre-ART and Early ART Adherence to Identify Key Factors Influencing Adherence Readiness.
Although current standard of care for HIV typically involves immediate initiation of antiretroviral therapy (ART), most patients can benefit from first assessing adherence readiness and addressing any barriers to optimal adherence. A sample of 176 HIV patients planning to start ART enrolled in a controlled trial of an adherence intervention that was based on the Information Motivation and Behavioral skills (IMB) model of health behavior. We examined correlates of multiple adherence readiness measures, as well as electronically measured early ART adherence, to identify variables most important for readiness to adhere well at the start of treatment. Education level, recency of HIV diagnosis and knowledge and commitment to adherence were found to be associated with both ART readiness and early ART adherence. These findings suggest that resources to support adherence readiness should target more experienced HIV patients, and strive to bolster knowledge and attitudes that reinforce commitment to adherence.


A rare case of giant coronary artery aneurysm in the context of multiple arterial aneurysms.
Whilst the incidence of CAA has been reported as up to 5%, giant CAA (>2cm) is rare. We present a rare case of 3cm×4cm giant coronary artery aneurysm (CAA) in the context of aorto-iliac aneurysmal disease, treated by staged open surgical repair. Abdominal aortic aneurysm (AAA) and CAA share risk factors and aetiological mechanisms, therefore should be considered, particularly when CAA is diagnosed in the first instance. Surgical intervention for diagnosed giant CAA appears to be the treatment of choice in the reported literature, with the order of intervention when AAA co-exists remaining a point for debate.


Selenium deficiency in low birth weight neonates: an unrecognized problem.
To determine whether selenium deficiency is common among low birth weight infants in our neonatal intensive care unit, we surveyed blood samples from healthy full-term and preterm infants born in our hospital over a 3-month period. Selenium was measured by electrothermal atomic absorption spectrometry. Glutathione peroxidase was measured in plasma by an automated method. Baseline (less than 72 hours postnatal) selenium concentration and glutathione peroxidase activity were significantly lower in low birth weight infants than in full-term babies. Sequential selenium analyses were obtained in 16 sick low birth weight neonates who remained in the intensive care nursery for up to 6 weeks because of lung disease. All were fed parenterally without supplemental selenium, with or without oral intake, for periods varying from 3 to 60 days. All had a marked decrease from baseline selenium levels, and values below the detection limit of our assay were found in seven infants. Selenium deficiency is much more common in small infants than is generally realized, but the clinical significance in neonates is poorly understood.


CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity.
Th17 cells play a critical role in host defense against extracellular pathogens and tissue homeostasis but can induce autoimmunity. The mechanisms implicated in balancing "pathogenic" and "non-pathogenic" Th17 cell states remain largely unknown. We used single-cell RNA-seq to identify CD5L/AIM as a regulator expressed in non-pathogenic, but not in pathogenic Th17 cells. Although CD5L does not affect Th17 differentiation, it is a functional switch that regulates the pathogenicity of Th17 cells. Loss of CD5L converts non-pathogenic Th17 cells into pathogenic cells that induce autoimmunity. CD5L mediates this effect by modulating the intracellular lipidome, altering fatty acid composition and restricting cholesterol biosynthesis and, thus, ligand availability for Rorγt, the master transcription factor of Th17 cells. Our study identifies CD5L as a critical regulator of the Th17 cell functional state and highlights the importance of lipid metabolism in balancing immune protection and disease induced by T cells.


Factors associated with timely COVID-19 vaccination in a population-based cohort of patients with cancer.
In many jurisdictions, cancer patients were prioritized for COVID-19 vaccination because of increased risk of infection and death. To understand sociodemographic disparities that affected timely receipt of COVID-19 vaccination among cancer patients, we undertook a population-based study in Ontario, Canada. Patients older than 18 years and diagnosed with cancer January 2010 to September 2020 were identified using administrative data; vaccination administration was captured between approval (December 2020) up to February 2022. Factors associated with time to vaccination were evaluated using multivariable Cox proportional hazards regression. The cohort consisted of 356 535 patients, the majority of whom had solid tumor cancers (85.9%) and were not on active treatment (74.1%); 86.8% had received at least 2 doses. The rate of vaccination was 25% lower in recent (hazard ratio [HR] = 0.74, 95% confidence interval [CI] = 0.72 to 0.76) and nonrecent immigrants (HR = 0.80, 95% CI = 0.79 to 0.81). A greater proportion of unvaccinated patients were from neighborhoods with a high concentration of new immigrants or self-reported members of racialized groups (26.0% vs 21.3%, standardized difference = 0.111, P < .001), residential instability (27.1% vs 23.0%, standardized difference = 0.094, P < .001), or material deprivation (22.1% vs 16.8%, standardized difference = 0.134, P < .001) and low socioeconomic status (20.9% vs 16.0%, standardized difference = 0.041, P < .001). The rate of vaccination was 20% lower in patients from neighborhoods with the lowest socioeconomic status (HR = 0.82, 95% CI = 0.81 to 0.84) and highest material deprivation (HR = 0.80, 95% CI = 0.78 to 0.81) relative to those in more advantaged neighborhoods. Despite funding of vaccines and prioritization of high-risk populations, marginalized patients were less likely to be vaccinated. Differences are likely due to the interplay between systemic barriers to access and cultural or social influences affecting uptake.


Endothelial alpha-parvin controls integrity of developing vasculature and is required for maintenance of cell-cell junctions.
Angiogenesis and vessel integrity depend on the adhesion of endothelial cells (ECs) to the extracellular matrix and to adjacent ECs. The focal adhesion protein α-parvin (α-pv) is essential for vascular development. However, the role of α-pv in ECs in vivo is not known. To determine the function of α-pv in ECs during vascular development in vivo and the underlying mechanisms. We deleted the α-pv gene specifically in ECs of mice to study its role in angiogenesis and vascular development. Here, we show that endothelial-specific deletion of α-pv in mice results in late embryonic lethality associated with hemorrhages and reduced vascular density. Postnatal-induced EC-specific deletion of α-pv leads to retinal hypovascularization because of reduced vessel sprouting and excessive vessel regression. In the absence of α-pv, blood vessels display impaired VE-cadherin junction morphology. In vitro, α-pv-deficient ECs show reduced stable adherens junctions, decreased monolayer formation, and impaired motility, associated with reduced formation of integrin-mediated cell-extracellular matrix adhesion structures and an altered actin cytoskeleton. Endothelial α-pv is essential for vessel sprouting and for vessel stability.


Prospective study of enteropathogens in children with diarrhea in Houston and Mexico.
During a 22-month period, 595 children with diarrhea and 210 age-matched controls attending clinics in Houston (367 children) and Mexico (438) were prospectively evaluated for enteric pathogens. Enteropathogens associated with disease were Shigella (18%), rotavirus (14%), Salmonella (9%), toxigenic Escherichia coli (6%), and others (12%), including 14 Proteus isolates that caused rounding of adrenal cells. Enteropathogens were isolated from a greater (P less than 0.001) number of children with diarrhea (59%) than from asymptomatic controls (6%). Paired sera tested for antibody to heat-labile toxin of E. coli rarely demonstrated a fourfold rise during episodes of diarrhea. This study demonstrates: (1) more striking illness in children from Mexico; (2) more common occurrence of Shigella in Houston, and of rotavirus and Salmonella in Mexico; (3) lack of seasonal occurrence of rotavirus isolation in either population and a summertime occurrence of Shigella in Houston; (4) lack of toxigenic E. coli isolation in endemic diarrhea of either population; and (5) a significant (P less than 0.001) age-related acquisition of E. coli LT antibodies.


Pathophysiological profiles of SDT fatty rats, a potential new diabetic peripheral neuropathy model.
To establish an animal model for diabetic peripheral neuropathy (DPN) at an earlier stage, we performed functional and pathophysiological evaluations in Spontaneously Diabetic Torii (SDT) fatty rats before 16weeks of age. Male SDT fatty rats were treated with vehicle or phlorizin (100 to 150mg/kg/day) from 5 to 16weeks. Sprague-Dawley (SD) rats were used as age-matched controls. Body weights and biochemical parameters were measured over time. During the treatment period, the sensory and motor nerve conduction velocity (SNCV and MNCV) of the sciatic nerve, blood pressure, pupil size, and electrocardiograms were measured. At 16weeks, the rats were sacrificed and sural nerves and intraepidermal nerves were sampled for histological studies, electron microscopic analysis and assessments of nerve fiber density. Functional abnormalities, such as delays of SNCV, increase of blood pressure, reduced pupillary reactivity, and decrease of the coefficient of variance of R-R intervals were observed in SDT fatty rats. Histopathologically, decreased intraepidermal nerve fiber density, mitochondrial abnormalities of small myelinated fibers, and vacuolation and mitochondrial swelling of unmyelinated fibers were found in SDT fatty rats. These changes were prevented by well-controlled blood glucose with phlorizin treatment. Male SDT fatty rats can help future work on DPN in diabetes with obesity, since this rat exhibited functional and pathological abnormalities in somatic and autonomic nerve from an early stage of diabetes.


The developmental viability and sizes of sequentially oviposited eggs of Boophilus decoloratus and Boophilus geigyi.
The viability and sizes of eggs sequentially laid up to the 10th day of oviposition by engorged Boophilus decoloratus and Boophilus geigyi were studied. The average length and breadth of eggs laid on the 1st and 2nd days of oviposition were statistically greater than at subsequent ovipositions. The eclosion periods of eggs laid from 7th to 10th day of oviposition were shorter than those of eggs laid earlier by both Boophilus species. The percentage mortality of eggs of 9th and 10th day of oviposition was significantly higher than that of the earlier ovipositions. The numbers of larvae which engorged on rabbits after hatching from eggs of 7th-10th day ovipositions were significantly fewer than those which hatched from eggs of earlier ovipositions. It is concluded that eggs of early ovipositions of B. decoloratus and B. geigyi are more viable and survive longer than those of later ovipositions. It is also suggested that the shorter eclosion period of the eggs of later ovipositions is due to the process of embryogenesis which is gradual in the eggs of early ovipositions and faster in those of later ovipositions.


The application of capillary gas chromatography-selective ion mass spectrometry for the separation, identification and quantification of phenolic bupivacaine metabolites from human urine.
A capillary gas chromatographic method has been developed and validated for the separation of phenolic metabolites from human urine following the intravenous infusion of racemic bupivacaine, with subsequent formal identification and quantification by on-line mass spectrometry.


Trends in the treatment of infected knee arthroplasty.
Essential treatment methods for infected knee arthroplasty involve DAIR (debridement, antibiotics, and implant retention), and one and two-stage exchange arthroplasty.Aggressive debridement with the removal of all avascular tissues and foreign materials that contain biofilm is mandatory for all surgical treatment modalities.DAIR is a viable option with an acceptable success rate and can be used as a first surgical procedure for patients who have a well-fixed, functioning prosthesis without a sinus tract for acute-early or late-hematogenous acute infections with no more than four weeks (most favourable being < seven days) of symptoms. Surgeons must focus on the isolation of the causative organism with sensitivities to bactericidal treatment as using one-stage exchange.One-stage exchange is indicated when the patients have:minimal bone loss/soft tissue defect allowing primary wound closure,easy to treat micro-organisms,absence of systemic sepsis andabsence of extensive comorbidities.There are no validated serum or synovial biomarkers to determine optimal timing of re-implantation for two-stage exchange.Antibiotic-free waiting intervals and joint aspiration before the second stage are no longer recommended. The decision to perform aspiration should be made based on the index of suspicion for persistent infection.Re-implantation can be performed when the treating medical team feels that the clinical signs of infection are under control and serological tests are trending downwards. Cite this article: EFORT Open Rev 2020;5:672-683. DOI: 10.1302/2058-5241.5.190069.


Spatial variability in threshold temperatures of heat wave mortality: impact assessment on prevention plans.
Spain's current heat wave prevention plans are activated according to administrative areas. This study analyses the determination of threshold temperatures for triggering prevention-plan activation by reference to isoclimatic areas, and describes the public health benefits. We subdivided the study area - the Madrid Autonomous Region (MAR) - into three, distinct, isoclimatic areas: 'North', 'Central' and 'South', and grouped daily natural-cause mortality (ICD-10: A00-R99) in towns of over 10,000 inhabitants (2000-2009 period) accordingly. Using these three areas rather than the MAR as a whole would have resulted in a possible decrease in mortality of 73 persons (38-108) in the North area, and in aborting unnecessary activation of the plan 153 times in the Central area and 417 times in the South area. Our results indicate that extrapolating this methodology would bring benefits associated with a reduction in attributable mortality and improved effectiveness of public health interventions.


Extractability and leachability of heavy metals in Technosols prepared from mixtures of unconsolidated wastes.
Mixtures of wastes were prepared to improve on the characteristics of the individual ingredients as Technosols, with special attention given to heavy metal extractability. An anaerobic digested sewage sludge and a CaO-treated aerobic sludge were used. A mixture of the two sludges (50:50 DW basis) was also prepared to provide a third type of sludge. The residues were mixed with other types of waste, such as fly ash, Linz-Donowitz slag, foundry sand, shot blasting machine scrap, fettling and barley straw. Extractability of Cu, Cr, Ni, and Zn by 0.01 M CaCl(2) extraction (Me(CACI(2)) was carried out, and leachability of these elements was estimated by acidification of an aqueous suspension of the mixtures with 0.5 N acetic acid (Me(acetic)). The total concentrations of the metals were also determined (Me(T)). The Me(CACI(2)/Me(T) ratios for Cu and Ni (means: 4.0% and 3.1%) were higher than those for Cr and Zn (means: 0.07% each). The mean Me(acetic)/Me(T) ratios followed the order Ni, Zn, Cu, and Cr (19.5%, 4.1%, 3.7%, and 0.09%, respectively). The results highlight the existence of complex interactions among organic matter solubility, pH and heavy metal extractability.


Results of aortic anastomoses made under tension using polydioxanone suture.
After early repair of congenital cardiovascular defects, such as coarctation of the aorta, late stenosis may become a problem. Use of absorbable sutures has been shown to be superior to use of nonabsorbable sutures in allowing growth of an anastomotic site along with the individual. Some concern has been raised, however, about the potential for aneurysm formation at the site of anastomosis when absorbable sutures are used. This study was undertaken to observe the effects of longitudinal tension on anastomoses made with absorbable polydioxanone suture in growing animals. Six piglets (aged 3 to 4 weeks) underwent a 1-cm resection of the infrarenal aorta and reanastomosis with polydioxanone suture. One animal died prematurely of respiratory illness. The 5 remaining animals were killed after 6 months. The excised aortas demonstrated no stenosis, no dilatation, and no burst-test failure to 250 mm Hg. Histological examination showed disrupted elastic laminae without thinning of aortic wall in all samples of aorta. We conclude that polydioxanone suture is a suitable suture material for vascular anastomoses made under tension where growth of the anastomotic site is expected.