Molecular characterization of AML-MRC reveals TP53 mutation as an adverse prognostic factor irrespective of MRC-defining criteria, TP53 allelic state, or TP53 variant allele frequency.
Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) generally confers poor prognosis, however, patient outcomes are heterogeneous. The impact of TP53 allelic state and variant allele frequency (VAF) in AML-MRC remains poorly defined. We retrospectively evaluated 266 AML-MRC patients who had NGS testing at our institution from 2014 to 2020 and analyzed their clinical outcomes based on clinicopathological features. TP53 mutations were associated with cytogenetic abnormalities in 5q, 7q, 17p, and complex karyotype. Prognostic evaluation of TP53MUT AML-MRC revealed no difference in outcome between TP53 double/multi-hit state and single-hit state. Patients with high TP53MUT variant allele frequency (VAF) had inferior outcomes compared to patients with low TP53MUT VAF. When compared to TP53WT patients, TP53MUT patients had inferior outcomes regardless of MRC-defining criteria, TP53 allelic state, or VAF. TP53 mutations and elevated serum LDH were independent predictors for inferior OS and EFS, while PHF6 mutations and transplantation were independent predictors for favorable OS and EFS. NRAS mutation was an independent predictor for favorable EFS. Our study suggests that TP53MUT AML-MRC defines a very-high-risk subentity of AML in which novel therapies should be explored.


Recent developments in HPLC analysis of β-blockers in biological samples.
β-Adrenergic blockers represent a very important class of drugs that are used worldwide for treating various cardiac diseases. The present article describes the state-of-the art of analyses of β-adrenergic blockers using high-performance liquid chromatography (HPLC). Sample preparation techniques such as liquid-liquid extraction, solid-phase extraction and solid-phase microextraction have been discussed, which are essential prior to HPLC analysis. Additionally, applications of liquid chromatography coupled with tandem mass spectrometry are included. HPLC methods have been reported to include 0.6-26 min as the run times and 0.01 ng/mL to 25 µg/mL as detection limits. The most commonly used columns were C18 with various buffers as the mobile phases, along with various organic modifiers. The optimization of HPLC conditions has been discussed. It has been observed that the reported methods are quite satisfactory for the analyses of β-adrenergic blockers in biological samples. Future perspectives in the hyphenation of solid-phase microextraction-nano-liquid chromatography-tandem mass spectrometry have also been highlighted to achieve detections at nanogram and picogram levels. The present article is very useful for academicians, scientists, drug and pharmaceutical personnel and government regulatory authorities.


Antral gastrin and acid secretion in duodenal ulcer patients.
By means of intragastric instillation of meat extract, two groups of duodenal ulcer patients were identified--antral responders and antral nonresponders. Antral response was abolished ater vagotomy and drainage or vagotomy-antrectomy. The differentiation would allow for selective surgery for duodenal ulcer patients.


Highly branched gold-copper nanostructures for non-enzymatic specific detection of glucose and hydrogen peroxide.
The development of highly sensitive and highly selective sensors for non-enzymatic glucose and hydrogen peroxide (H2O2) detection using gold-copper alloy nanoparticles (AuCu alloy NPs) is reported. The AuCu NPs are nanostructures with branches and can be used as an electrochemical catalyst. Series of AuCu alloy NPs with various metal ratios are synthesized through a coreduction reaction. The morphology of AuCu alloy NPs is altered from highly branched structures (nanourchin, nanobramble, nanostar, nanocrystal) to a spherical shape by increasing Au content in the synthesis reaction. Cu-rich AuCu nanobramble and Au-rich AuCu nanostar exhibit selective electrocatalysis behaviors toward electro-oxidation of glucose and electroreduction of H2O2, respectively. The AuCu nanobramble-based sensor holds great potential in glucose detection with a linear working range of 0.25 to 10 mM. The sensor possesses a sensitivity of 339.35 μA mM-1 cm-2, a limit of detection (LOD) of 16.62 μM, which is an acceptable selectivity and good stability. In addition, the AuCu nanostar-based sensor shows excellent electrochemical responses toward H2O2 reduction with good selectivity, reproducibility, and a short response time of about 2-3 s. The linear range for H2O2 determination is 0.05 to 10 mM, with LOD and sensitivity of 10.93 μM and 133.74 μA mM-1 cm-2, respectively. The good sensing performance is a result of the synergistic surface structure and atomic composition effects, which leads AuCu alloys to be a promising nanocatalyst for sensing both glucose and H2O2. Graphical abstract Schematic illustration presents the construction of gold-copper alloy nanoparticles (AuCu alloy NPs) on the surface of screen-printed carbon electrode (SPCE). The highly branched nanostructures of AuCu alloys with different surface structure and metal ratios give selective electrocatalysis behaviors. Cu-rich AuCu nanobramble-based sensor reveals prominent electrocatalytic activity for glucose detection. Au-rich AuCu nanostar-based sensor provides good electrochemical response for H2O2 detection.


Utilization of Portland cement with limestone powder and cement kiln dust for stabilization/solidification of oil-contaminated marl soil.
Stabilization/solidification (S/S) is a technique that has been widely used to treat contaminated soils using several types of stabilizers, such as ordinary Portland cement (OPC). In this research, marl soil that was collected from eastern Saudi Arabia was contaminated by either diesel or crude oil at different dosages (i.e., 2.5, 5, and 10% by the dry weight of the soil) and tested to assess its geotechnical and environmental properties. Thereafter, the contaminated soil was stabilized using OPC, limestone powder (LSP), and cement kiln dust (CKD) at different proportions. The contaminated-stabilized soils were evaluated by measuring the changes in their geotechnical properties, and both metal and hydrocarbon contents. Results of this investigation indicated that the S/S treatment of the contaminated soils enhanced the compaction characteristics with a significant improvement in the unconfined compressive strength (UCS) results, and all of S/S-treated mixtures were found to pass the strength criterion of the U.S. Environmental Protection Agency (USEPA) (i.e., 340 kPa after 28 days of curing). Moreover, The UCS results of the stabilized soils were compared to the minimum strength requirements for both paved and unpaved road materials (i.e., 1380 and 690 kPa, respectively). Finally, scanning electron microscope (SEM) with energy dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD) analyses were used to elucidate the changes in the microstructure of the stabilized soils.


Sex-related quality of life after total laryngectomy for cancer.
Analysis of the quality of sexual life after total laryngectomy (TL) for cancer. The Cochrane, PubMed, Embase, ClinicalKey and Science Direct databases were searched using the keywords: "total laryngectomy, sexual function, sexual behavior, sexual complications, sexual dysfunction, sexuality, intimacy". The abstracts of 69 articles were read by two of the authors and 24 articles were selected. The main endpoint was the impact of impairment of quality of sexual life after TL for cancer and the methods used to assess this. The secondary endpoints were the type of sexual impairment, associated variables and their treatment. The study population consisted of 1511 TL patients aged 21 to 90 years, with a male/female sex ratio of 7.49. One of the 7 validated Likert scales was used in 79% of the articles to evaluate impairment of sexual quality of life. Impaired quality of sexual life was reported by 47% of patients on average (range, 5-90%). Erectile and ejaculatory function and ejaculatory behavior of male patients decreased after TL. Other impairments comprised decreases in libido, frequency of sexual intercourse and satisfaction. Tracheostomy, advanced disease stage, young age and associated depression were factors for impairment. In all, 23% of patients reported lack of postoperative support in this area. The quality of sexual life is severely impacted by TL for cancer. The present data are a source of information and should be taken into account before carrying out TL. A common information tool needs to be developed. There is patient demand for improved management of sexuality.


Design, synthesis, in vitro antimicrobial and anticancer activity of novel methylenebis-isoxazolo[4,5-b]azepines derivatives.
A series of novel methylene bis-isoxazolo[4,5-b]azepines have been synthesized by reaction of 3,5-dimethyl-4-nitroisoxazole 6 with an appropriate methylene bis-chalcones 7 to obtain various Michael adducts 8a-i, which on treatment with SnCl(2)-MeOH underwent reductive cyclization to afford the title compounds 9a-i. Structure of these compounds were established on the basis of IR, (1)H NMR, (13)C NMR and mass spectral data. The title compounds 9a-i were evaluated for their in vitro antimicrobial and anticancer activities. Compounds 9h and 9i exhibited potent antimicrobial and anticancer activities as that of standard drugs.


Paeoniflorin promotes intestinal stem cell-mediated epithelial regeneration and repair via PI3K-AKT-mTOR signalling in ulcerative colitis.
Ulcerative colitis (UC) is a chronic and immune-mediated inflammatory disorder characterized by abdominal pain, diarrhoea, and haematochezia. The goal of clinical therapy for UC is mucosal healing, accomplished by regenerating and repairing the intestinal epithelium. Paeoniflorin (PF) is a natural ingredient extracted from Paeonia lactiflora that has significant anti-inflammatory and immunoregulatory efficacy. In this study, we investigated how PF could regulate the renewal and differentiation of intestinal stem cells (ISCs) to improve the regeneration and repair of the intestinal epithelium in UC. Our experimental results showed that PF significantly alleviated colitis induced by dextran sulfate sodium (DSS) and ameliorated intestinal mucosal injury by regulating the renewal and differentiation of ISCs. The mechanism by which PF regulates ISCs was confirmed to be through PI3K-AKT-mTOR signalling. In vitro, we found that PF not only improved the growth of TNF-α-induced colon organoids but also increased the expression of genes and proteins related to the differentiation and regeneration of ISCs. Furthermore, PF promoted the repair ability of lipopolysaccharide (LPS)-induced IEC-6 cells. The mechanism by which PF regulates ISCs was further confirmed and was consistent with the in vivo results. Overall, these findings demonstrate that PF accelerates epithelial regeneration and repair by promoting the renewal and differentiation of ISCs, suggesting that PF treatment may be beneficial to mucosal healing in UC patients.


The relationship of detergent-solubilization plasma-membrane components of rabbit alveolar macrophages to an isolated inhibitor of phagocytosis.
1. A plasma-membrane fraction prepared from rabbit alveolar macrophages by hyposmotic borate lysis is described. 2. Rabbit lung lavages, containing a glycoprotein inhibitor of phagocytosis, may be fractionated by preparative isoelectric focusing in the presence of Triton X-100. 3. Chemical analysis indicates that the glycoproteins of the lung lavage contain sialic acid, fucose, mannose, galactose, hexosamine and appreciable quantities of glucose. 4. The relationship of macrophage membrane glycoproteins, solubilized with Triton X-100 in the presence of borate, to the lung lavage glycoproteins is demonstrated immunoelectrophoretically.


More to ADHD than meets the eye: observable abnormalities in search behaviour do not account for performance deficits on a discrimination task.
Children with Attention Deficit/Hyperactivity Disorder (ADHD) often perform poorly on tasks requiring sustained and systematic attention to stimuli for extended periods of time. The current paper tested the hypothesis that such deficits are the result of observable abnormalities in search behaviour (e.g., attention-onset, -duration and -sequencing), and therefore can be explained without reference to deficits in non-observable (i.e., cognitive) processes. Forty boys (20 ADHD and 20 controls) performed a computer-based complex discrimination task adapted from the Matching Familiar Figures Task with four different fixed search interval lengths (5-, 10-, 15- and 20-s). Children with ADHD identified fewer targets than controls (p < 0.001), initiated searches later, spent less time attending to stimuli, and searched in a less intensive and less systematic way (p's < 0.05). There were significant univariate associations between ADHD, task performance and search behaviour. However, there was no support for the hypothesis that abnormalities in search carried the effect of ADHD on performance. The pattern of results in fact suggested that abnormal attending during testing is a statistical marker, rather than a mediator, of ADHD performance deficits. The results confirm the importance of examining covert processes, as well as behavioural abnormalities when trying to understand the psychopathophyiology of ADHD.


Predictability of Motor Outcome According to the Time of Motor Evoked Potentials From the Onset of Stroke in Patients With Putaminal Hemorrhage.
To determine the predictability of motor evoked potentials (MEP) in patients with putaminal hemorrhage (PH) according to the time of MEP from the onset of stroke. Sixty consecutive patients with PH from January 2006 to November 2013 were retrospectively reviewed. Motor function of affected extremities was measured at onset time and at six months after the onset. Patients were classified into two groups according to the time of MEP from the onset of stroke: early MEP group (within 15 days from onset) and late MEP group (16-30 days from onset). Patients were also classified into two groups according to the presence of MEP on the affected abductor pollicis brevis (APB): MEP (+) group-patients (showing MEP in the affected APB) and MEP (-) group-patients (no MEP in the affected APB). Motor outcome was compared between the two early and late MEP groups or between the presence and absence of MEP in the affected APB groups. For patients with MEP (+), a larger portion in the late MEP group showed good prognosis compared to the early MEP group (late MEP, 94.4%; early MEP, 80%). In contrast, in patients with MEP (-), a larger portion of patients in the late MEP group showed bad prognosis compared to the early MEP group (late MEP, 80%; early MEP, 71.4%). No significant improvement of MI between MEP (+) and MEP (-) was observed when MEP was performed early or late. Our results revealed that the predictability of motor outcome might be better if MEP is performed late compared to that when MEP is performed early in patients with PH.


Time-Controlled Colloidal Superstructures: Long-Range Plasmon Resonance Coupling in Particle Monolayers.
Particle interactions, from pronounced dipolar plasmon coupling to noncoupling in colloidal monolayers with interparticle distances of hundreds of nanometers, are demonstrated. Macroscopically sized, hexagonal monolayers with exceptionally high degrees of order are fabricated in one step. Time controls the interparticle spacing and no further processing is required.


Acute diverticulitis: an ongoing economic burden on the health system.
Acute diverticulitis (AD) is an increasingly common cause of acute hospital admissions. An understanding of its economic burden is necessary to plan resource allocation, and for targeting health research funding. The aim of this study is to obtain an accurate estimate of the cost of AD, accounting not only for the initial episode, but all related costs incurred during long-term follow-up. The study captures a cohort of patients who had an initial admission for AD from 1 January 2012-31 December 2012, and their treatment over a 6-year period. Cases were identified from a prospectively maintained database, with AD confirmed by computed tomography scan. The primary outcome was total healthcare cost related to AD. The study included 170 patients. The total cost was NZD1 956 859 with a median cost per patient of NZD4814. A total of 57% of the cost was incurred for the initial inpatient admission, with the remaining 43% incurred through re-admission, follow-up appointments, investigations and management. Half of the total cost was incurred by 11.8% of the cohort. In multivariate analysis, high cost of care was significantly associated with complicated and recurrent disease, operative intervention and length of stay. This study provides an accurate estimate of the overall cost of AD and its sequelae. There are considerable long-term costs associated with the index episode and a large proportion of the expenditure is incurred by a small group that included those with complicated disease. These findings are important for healthcare resource allocation and for targeting health research funding.


Large-scale forest fragmentation increases the duration of tent caterpillar outbreak.
I examined historical data (1950-1984) on the duration of outbreaks of the forest tent caterpillar (Malacosoma disstria) in northern Ontario, Canada. Outbreak duration was compared to host tree species dominance and forest structure over large areas of boreal forest partially cleared for agriculture. Abundance of the principal host tree species Populus tremuloides had no consistent effect on duration of outbreak within forest districts, and was negatively correlated with duration of outbreaks among the eight forest districts examined. The amount of forest edge per km2 was the best, and most consistent, predictor of the duration of tent caterpillar outbreaks both within individual forest districts and among forest districts. Because forest tent caterpillar populations are driven largely by the impact of parasitoids and pathogens, results here suggest that large-scale increase in forest fragmentation affects the interaction between these natural enemies and forest tent caterpillar. Increased clearing and fragmentation of boreal forests, by agriculture and forestry, may be exacerbating outbreaks of this forest defoliator.


Pre-diagnostic 25-hydroxyvitamin D levels and survival in cancer patients.
Our main aim was to explore whether pre-diagnostic circulating levels of 25-hydroxyvitamin D (25(OH)D) among older individuals with cancer were associated with overall and cancer-specific survival after diagnosis. We used data from the Reykjavik-AGES Study on participants (n = 4,619) without cancer at entry, when blood samples were taken for 25(OH)D standardized measurements. The association with cancer risk, all-cause- and cancer-specific mortality was assessed among those later diagnosed with cancer, comparing four 25(OH)D categories, using 50-69.9 nmol/L as the reference category. Cancer was diagnosed in 919 participants on average 8.3 years after blood draw. No association was observed between the reference group and other 25(OH)D groups and total cancer incidence. Mean age at diagnosis was 80.9 (± 5.7) years. Of those diagnosed, 552 died during follow-up, 67% from cancer. Low pre-diagnostic levels of 25(OH)D < 30 nmol/L were significantly associated with increased total mortality (HR: 1.39, 95% CI 1.03, 1.88) and non-significantly with cancer-specific mortality (HR: 1.33, 95% CI 0.93, 1.90). Among patients surviving more than 2 years after diagnosis, higher pre-diagnostic 25(OH)D levels (≥ 70 nmol/L) were associated with lower risk of overall (HR: 0.68, 95% CI 0.46, 0.99) and cancer-specific mortality (HR: 0.47, 95% CI 0.26, 0.99). Among elderly cancer patients, low pre-diagnostic serum 25(OH)D levels (< 30 nmol/L) were associated with increased overall mortality.


Mechanistic details of the actinobacterial lyase-catalyzed degradation reaction of 2-hydroxyisobutyryl-CoA.
Actinobacterial 2-hydroxyacyl-CoA lyase reversibly catalyzes the thiamine diphosphate-dependent cleavage of 2-hydroxyisobutyryl-CoA to formyl-CoA and acetone. This enzyme has great potential for use in synthetic one-carbon assimilation pathways for sustainable production of chemicals, but lacks details of substrate binding and reaction mechanism for biochemical reengineering. We determined crystal structures of the tetrameric enzyme in the closed conformation with bound substrate, covalent postcleavage intermediate, and products, shedding light on active site architecture and substrate interactions. Together with molecular dynamics simulations of the covalent precleavage complex, the complete catalytic cycle is structurally portrayed, revealing a proton transfer from the substrate acyl Cβ hydroxyl to residue E493 that returns it subsequently to the postcleavage Cα-carbanion intermediate. Kinetic parameters obtained for mutants E493A, E493Q, and E493K confirm the catalytic role of E493 in the WT enzyme. However, the 10- and 50-fold reduction in lyase activity in the E493A and E493Q mutants, respectively, compared with WT suggests that water molecules may contribute to proton transfer. The putative catalytic glutamate is located on a short α-helix close to the active site. This structural feature appears to be conserved in related lyases, such as human 2-hydroxyacyl-CoA lyase 2. Interestingly, a unique feature of the actinobacterial 2-hydroxyacyl-CoA lyase is a large C-terminal lid domain that, together with active site residues L127 and I492, restricts substrate size to ≤C5 2-hydroxyacyl residues. These details about the catalytic mechanism and determinants of substrate specificity pave the ground for designing tailored catalysts for acyloin condensations for one-carbon and short-chain substrates in biotechnological applications.


Arginine 26 and aspartic acid 69 of the regulatory subunit are key residues of subunits interaction of acetohydroxyacid synthase isozyme III from E. coli.
Acetohydroxyacid synthase (AHAS), which catalyzes the first step in the biosynthesis of branched-chain amino acids, is composed of catalytic and regulatory subunits. The enzyme exhibits full activity only when the regulatory subunit (RSU) binds to the catalytic subunit (CSU). However, the crystal structure of the holoenzyme has not been reported yet, and the molecular interaction between the CSU and RSU is also unknown. Herein, we introduced a global-surface, site-directed labeling scanning method to determine the potential interaction region of the RSU. This approach relies on the insertion of a bulky fluorescent probe at the designated site on the surface of the RSU to cause a dramatic change in holoenzyme activity by perturbing subunit interaction. Then, the key amino acid residues in the potential interaction regions were identified by site-directed mutagenesis. Compared to the wild-type, the single-point mutants R26A and D69A showed 54 and 64 % activity, respectively, whereas the double mutant (R26A+D69A) gave 14 %, thus suggesting that residues Arg26 and Asp69 are the key residues of subunit interaction with cooperative action. Additionally, the results of GST pull-down assays and pH-dependence experiments suggested that polar interaction is the main force for subunits interaction. A plausible protein-protein interaction model of the holoenzyme of Escherichia coli AHAS III is proposed, based on the mutagenesis and protein docking studies. The protocol established here should be useful for the identification of the molecular interactions between proteins.


A phase II trial (AGO 2.11) in platinum-resistant ovarian cancer: a randomized multicenter trial with sunitinib (SU11248) to evaluate dosage, schedule, tolerability, toxicity and effectiveness of a multitargeted receptor tyrosine kinase inhibitor monotherapy.
Recurrent platinum-resistant ovarian cancer usually has a poor outcome with conventional chemotherapeutic therapy and new treatment modalities are warranted. This phase II study was conducted to evaluate sunitinib, an oral antiangiogenic multitargeted tyrosin kinase inhibitor, in this setting. The primary end point of this randomized phase II trial was the objective response rate according to RECIST criteria and/or Gynecologic Cancer InterGroup CA125 response criteria to sunitinib in patients with recurrent platinum-resistant ovarian cancer who were pretreated with up to three chemotherapies. A selection design was employed to compare two schedules of sunitinib (arm 1: 50 mg sunitinib daily orally for 28 days followed by 14 days off drug; and arm 2: 37.5 mg sunitinib administered daily continuously). Of 73 patients enrolled, 36 patients were randomly allocated to the noncontinuous treatment arm (arm 1) and 37 patients were randomly allocated to the continuous treatment arm (arm 2). The mean age was 58.8 and 58.5 years, respectively. We observed six responders (complete response + partial response) in arm 1 (16.7%) and 2 responders in arm 2 (5.4%). The median progression-free survival (arm 1: 4.8 [2.9-8.1] months; arm 2: 2.9 [2.9-5.1] months) and the median overall survival (arm 1: 13.6 [7.0-23.2] months; arm 2: 13.7 [8.4-25.6] months) revealed no significant difference. Adverse events included fatigue as well as cardiovascular, gastrointestinal and abdominal symptoms, hematologic and hepatic laboratory abnormalities. Pattern and frequency of adverse events revealed no substantial differences between both treatment groups. Sunitinib treatment is feasible and moderately active in relapsed platinum-resistant ovarian cancer. The noncontinuous treatment schedule should be chosen for further studies in ovarian cancer.


Radiographic Evaluations of Revision Total Knee Arthroplasty: A Plea for Uniform Assessments.
Thorough radiographic evaluation is necessary for perioperative assessments in revision total knee arthroplasty. There has been a large degree of variability in reporting these findings within the peer-reviewed literature. Our purpose was to evaluate studies that radiographically assessed alignment in the coronal and sagittal plane, patella alignment and thickness, presence and characterization of implant interface, and radiolucency. Secondly, we reviewed studies using a standardized reporting system to evaluate radiographic findings (the Knee Society Roentgenographic Evaluation and Scoring System) and the number of times it was referenced. Only 62% of studies evaluated all radiographic parameters, 57% to 91% assessed each metric, and 55% used standardized reporting systems. This emphasizes the need for a uniform evaluation method to ensure consistent radiographic assessment and optimal standard of care.


Electrospinning fabrication of Sb-SnSb/TiO2@CNFs composite nanofibers as high-performance anodes for lithium-ion batteries.
The SnSb and TiO2 nanoparticles uniformly embedded into continuous and conductive carbon nanofibers (CNFs) are successfully fabricated through facile electrospinning combined with calcination treatments. The characterization results of the targeted composite nanofibers (Sb-SnSb/TiO2@CNFs-2) confirm that the presence of TiO2 is of significant importance to construct the elaborately designed and intact fiber structure, in which the optimal dosage of the TiO2 precursor is precisely controlled at 2 mmol. Moreover, high theoretical specific capacity of SnSb, available inhibitory effect of TiO2, and great electronic conductivity of CNFs are cooperatively integrated into the Sb-SnSb/TiO2@CNFs-2 composite nanofibers, guaranteeing the enhanced lithium storage capacity and cycling performance when being employed as the anode electrodes. Specifically, the Sb-SnSb/TiO2@CNFs-2 electrode can not only deliver initial discharge specific capacity of 1146.6 mAh/g at 100 mA/g and reversible discharge specific capacity of 580.4 mAh/g after 100 cycles, but also retain discharge specific capacity of 561.3 mAh/g after rate cycles along with recovering the current density to 100 mA/g. Importantly, the Sb-SnSb/TiO2@CNFs-2 electrode is also endowed with prominent advantages in the pseudocapacitive contribution of 66.89 % at 0.8 mV/s. Those investigations and findings of the Sb-SnSb/TiO2@CNFs-2 composite electrodes with facile fabrication process and excellent electrochemical performance can contribute to the practical application of the alloy anodes in the field of the energy storage.


Toxicity effect of graphene oxide on growth and photosynthetic pigment of the marine alga Picochlorum sp. during different growth stages.
Graphene oxide (GO), a recently discovered material, has been investigated for many applications in various fields. Thus, an immense awareness should be paid on the potential effects of the material on the environment as huge quantities of GO may get to the environment. Aquatic organisms, marine algae as an example, are exposed to such material when disposed to the environment. Accordingly, it is significant to assess the probable interactions of GO with algae in evaluating its possible environmental risks. In this study, we have examined the effect of different concentrations of GO on Picochlorum sp. during the different growth phases. The results showed that the toxicity of GO increases with increasing its concentration. The lowest concentration (0.5 mg L-1) was found to improve the algae growth and pigment content of Picochlorum sp. In contrast, higher GO concentrations had a negative consequence on the growth of algae and photosynthetic pigment concentration.


One year outcomes of atrial fibrillation ablation: Contemporary analysis of the United States Nationwide Readmission Database.
Data on long-term outcomes of catheter ablation (CA) for atrial fibrillation (AF) in outside of clinical trials settings are sparse. We aimed to assess outcomes and readmissions at 1 year following admission for CA for AF. Utilizing the Nationwide Readmissions Database (2016-2018), we identified patients with CA among all patients with a primary admission diagnosis of AF, and a control group by propensity score match adjusted for age, sex, comorbidities, CHA₂DS₂-VASc scores, and the hospital characteristics. The primary outcome was a composite of unplanned heart failure (HF), AF and stroke-related readmissions, and death at 1 year, and secondary outcomes were hospital outcomes and all-cause readmission rates. The study cohort consisted of 29,771 patients undergoing CA and 63,988 controls. Patients undergoing CA were younger with lower CHA₂DS₂-VASc scores and less comorbidities. Over a follow-up of 170 ±1.1 days, the primary outcome occurred in 5.2% in CA group and 6.0% of controls (hazard ratio [HR] and 95% confidence interval [CI]: 0.86 [0.76-0.94], p = .002). CA affected AF and stroke related readmission, but showed no effect on HF and mortality outcome. Male sex (HR: 0.83 [0.74-0.94], p = .03), younger age (HR: 0.71 [0.61-0.83], p < .001], and lower CHA₂DS₂-VASc scores (HR: 0.68 [0.55-0.84], p < .001) were associated with lower risk of primary outcome with CA. In this study, CA for AF was associated with significantly lower AF and stroke-related admissions, but not to HF or all-cause readmission. Better outcomes were seen among males, younger patients, and in patients with less comorbidities and low CHA₂DS₂-VASc scores.


First-in-Human Closed-Chest Transcatheter Superior Cavopulmonary Anastomosis.
In the care of patients with congenital heart disease, percutaneous interventional treatments have supplanted many surgical approaches for simple lesions, such as atrial septal defect. By contrast, complex congenital heart defects continue to require open-heart surgery. In single-ventricle patients, a staged approach is employed, which requires multiple open-heart surgeries and significant attendant morbidity and mortality. A nonsurgical transcatheter alternative would be attractive. The authors sought to show the feasibility of catheter-only, closed-chest, large-vessel anastomosis (superior vena cava and pulmonary artery [PA] or bidirectional Glenn operation equivalent) in a patient. In preclinical testing over a decade, the authors developed the techniques and technology needed for nonsurgical crossing from a donor (superior vena cava) to a recipient (PA) vessel and endovascular stent-based anastomosis of those blood vessels. The authors undertook this transcatheter approach for an adult with untreated congenital heart disease with severe cyanosis and significant surgical risk. They rehearsed the procedure step by step using contrast-enhanced cardiac computed tomography and a patient-specific 3-dimensional printed heart model. The authors describe a first-in-human, fully percutaneous superior cavopulmonary anastomosis (bidirectional Glenn operation equivalent). The patient, a 35-year-old woman, was homebound due to dyspnea and worsening cyanosis. She was diagnosed with functional single ventricle and very limited pulmonary blood flow. The heart team believed surgical palliation conferred high operative risk due to the patient's complete condition. With the percutaneous procedure, the patient recovered uneventfully and remained improved clinically after 6 months. This procedure may provide a viable alternative to one of the foundational open-heart surgeries currently performed to treat single-ventricle congenital heart disease.


Combined GWAS and QTL mapping revealed candidate genes and SNP network controlling recovery and tolerance traits associated with drought tolerance in seedling winter wheat.
To date, very little research on drought tolerance has been conducted at the seedling stage in winter wheat. In this study, two types of traits, namely tolerance and recovery traits, associated with drought tolerance were scored in biparental mapping population (BPP) and association mapping population (A-set). The results of this study revealed no or weak significant correlation between the two types of traits. Based on GWAS and QTL mapping analyses, all QTLs associated with recovery traits were completely different from those associated with tolerance traits except one QTL in each population that was found to be associated with one tolerance trait and one recovery trait. The analysis of SNP and gene networks confirmed the results of combined GWAS and QTL mapping. One SNP marker located on the 2B chromosome (S2B_26494801) was found to be associated with recovery traits in both populations. The results of this study provided new information on understanding and improving drought tolerance in winter wheat.


Outcomes using a bioprosthetic mesh at the time of permanent stoma creation in preventing a parastomal hernia: a value analysis.
A retrospective review of the medical records of all patients who had a prosthetic placed at the time of stoma creation for the prevention of a parastomal hernia was performed. The purpose of this study was to evaluate the safety, efficacy, and cost-effectiveness of bioprosthetics. A bioprosthetic was used in 16 patients to prevent the occurrence of a parastomal hernia. The median follow-up was 38 months. There were no mesh-related complications, and no parastomal hernias occurred. On value analysis, to be cost-effective, the percentage of patients who would have subsequently needed surgical repair of a parastomal hernia would have to be in excess of 39% or the bioprosthetic would have to cost less than $2,267 to $4,312. These data show the safety and efficacy of using a bioprosthetic at the time of permanent stoma creation in preventing a parastomal hernia and defines the parameters for this approach to be cost-effective.


Quantitative microbial risk assessment of SARS-CoV-2 for workers in wastewater treatment plants.
Faecal-oral transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is yet to be validated, but it is a critical issue and additional research is needed to elucidate the risks of the novel coronavirus in sanitation systems. This is the first study that investigates the potential health risks of SARS-CoV-2 in sewage to wastewater treatment plant (WWTP) workers. A quantitative microbial risk assessment (QMRA) is applied for three COVID-19 scenarios (moderate, aggressive and extreme) to study the effects of different stages of the pandemic in terms of percentage of infected population on the probability of infection to WWTP workers. A dose-response model for SARS-CoV-1 (as a surrogate pathogen) is assumed in the QMRA for SARS-CoV-2 using an exponential model with k = 4.1 × 102. Literature data are incorporated to inform assumptions for calculating the viral load, develop the model, and derive a tolerable infection risk. Results reveal that estimates of viral RNA in sewage at the entrance of WWTPs ranged from 4.14 × 101 to 5.23 × 103 GC·mL-1 (viable virus concentration from 0.04 to 5.23 PFU·mL-1, respectively). In addition, estimated risks for the aggressive and extreme scenarios (2.6 × 10-3 and 1.3 × 10-2, respectively) were likely to be above the derived tolerable infection risk for SARS-CoV-2 of 5.5 × 10-4 pppy, thus reinforcing the concern of sewage systems as a possible transmission pathway of SARS-CoV-2. These findings are helpful as an early health warning tool and in prioritizing upcoming risk management strategies, such as Emergency Response Plans (ERPs) for water and sanitation operators during the COVID-19 and future pandemics.


Incidences of complications associated with cervical cerclage by indication of the procedure.
To investigate the incidence of complications associated with cervical cerclage by indication. This was a retrospective cohort study of women with singleton pregnancies who underwent cervical cerclage in a single perinatal center between 2008 and 2019. The participants were divided into three groups according to indication: history-indicated cerclage (HIC) group, ultrasound-indicated cerclage (UIC) group, and physical examination-indicated cerclage (PEIC) group. The incidences of perioperative complications within 2 weeks after the procedure, including intraoperative rupture of membranes, intraoperative bleeding, anesthesia complications, clinical chorioamnionitis, premature rupture of membranes (PROM), preterm delivery, and displacement of the suture, and those of peripartum complications, including difficult suture removal and cervical laceration, for each group were compared using Fisher's exact test or Pearson's chi-square test. Factors associated with severe adverse event, defined as PROM or delivery within 2 weeks after the procedure, were analyzed using multivariate logistic regression analysis. A total of 279 women (HIC, 38; UIC, 96; PEIC, 145) were enrolled. The incidence of perioperative complications was different among the three groups (7.9%, 10.4%, and 27.6%, respectively; p < 0.01), whereas that of peripartum complications was similar (18.4%, 11.5%, and 12.4%, respectively; p = 0.54). Severe adverse events occurred only in PEIC group, with an incidence of 18.6%. The associated factor for severe adverse events in PEIC group was prolapsed membranes into the vagina. Incidences of perioperative complications of cerclage differed among the indications. Women who underwent PEIC had higher risk of severe adverse events, especially when accompanied with prolapsed membranes into the vagina.


Maxillofacial and Mandibular Fractures in Sports.
Sports account for 3% to 29% of facial injuries and 10% to 42% of facial fractures. Fractures of the facial skeleton most commonly occur owing to interpersonal violence or motor vehicle crashes. Facial fractures from sporting activities has clearly decreased over time owing to better preventive measures. However, this decreasing trend is offset by the emergence of more dangerous sports activities, or "pushing the envelope" of traditional sports activities. Fractures can occur from contact between athletes, and between athletes and their surroundings. Football, soccer, hockey, and baseball most frequently are involved in sports-related cases of facial bone fracture.


High efficiency of ROS production by glycerophosphate dehydrogenase in mammalian mitochondria.
We investigated hydrogen peroxide production in mitochondria with low (liver, heart, brain) and high (brown adipose tissue, BAT) content of glycerophosphate dehydrogenase (mGPDH). ROS production at state 4 due to electron backflow from mGPDH was low, but after inhibition of electron transport with antimycin A high rates of mGPDH-dependent ROS production were observed in liver, heart and brain mitochondria. When this ROS production was related to activity of mGPDH, many-fold higher ROS production was found in contrast to succinate- (39-, 28-, 3-fold) or pyruvate plus malate-dependent ROS production (32-, 96-, 5-fold). This specific rate of mGPDH-dependent ROS production was also exceedingly higher (28-, 66-, 22-fold) compared to that in BAT. mGPDH-dependent ROS production was localized to the dehydrogenase+CoQ and complex III, the latter being the highest in all mitochondria but BAT. Our results demonstrate high efficiency of mGPDH-dependent ROS production in mammalian mitochondria with a low content of mGPDH and suggest its endogenous inhibition in BAT.


Fate of volatile aromatic hydrocarbons in the wastewater from six textile dyeing wastewater treatment plants.
The occurrence and removal of benzene, toluene, ethylbenzene, xylenes, styrene and isopropylbenzene (BTEXSI) from 6 textile dyeing wastewater treatment plants (TDWTPs) were investigated in this study. The practical capacities of the 6 representative plants, which used the activated sludge process, ranged from 1200 to 26000 m(3) d(-1). The results indicated that BTEXSI were ubiquitous in the raw textile dyeing wastewater, except for isopropylbenzene, and that toluene and xylenes were predominant in raw wastewaters (RWs). TDWTP-E was selected to study the residual BTEXSI at different stages. The total BTEXSI reduction on the aerobic process of TDWTP-E accounted for 82.2% of the entire process. The total BTEXSI concentrations from the final effluents (FEs) were observed to be below 1 μg L(-1), except for TDWTP-F (2.12 μg L(-1)). Volatilization and biodegradation rather than sludge sorption contributed significantly to BTEXSI removal in the treatment system. BTEXSI were not found to be the main contaminants in textile dyeing wastewater.


Population structure and responses to disturbance of the basidiomycete Resinicium bicolor.
Resinicium bicolor (Alb. & Schw. ex Fr.) Parm. [=Odontia bicolor (Alb. & Schw. ex Fr.) Bres.] is an outcrossing resupinate basidiomycete associated with root and butt rots of trees, but is itself only very weakly pathogenic. The distribution of genets among every spruce stump in a 70-year-old 1250 m2 spruce stand was analysed using somatic incompatibility testing. R. bicolor was present on 40% of 8-to 10-year-old stumps. Nineteen genets were found occupying 32 stumps; yielding probabilities of colonisation following establishment by basidiospores of 0.20-0.24 and by mycelial extension or dispersal of 0.16-0.20. The probability of colonisation decreased with increasing distance from a point of establishment. R. bicolor responded to both enrichment and destructive disturbances by the formation of an extensive cord system which enabled it to colonise discontinuously distributed resources and to overgrow fungi adjacent to it in a single resource unit, including Heterobasidion annosum.


Controlled transient changes reveal differences in metabolite production in two Candida yeasts.
Physiological responses during growth on xylose and the xylose-degrading pathway of Candida tropicalis and Candida guilliermondii yeasts were investigated. The responses to a linearly decreasing oxygen transfer rate and a simultaneously increasing dilution rate were compared. C. guilliermondii produced acetate but no ethanol, and C. tropicalis ethanol but no acetate under oxygen limitation. Both strains produced glycerol. The D-xylose reductase of C. guilliermondii is exclusively NADPH-dependent. and acetate production regenerated NADPH. The xylose'reductase of C. tropicalis has a dual dependency for both NADH and NADPH. It regenerated NAD by producing ethanol. Both strains regenerated NAD by producing glycerol. The effect of intracellular NADH accumulation to xylose uptake and metabolite production was studied by using formate as a cosubstrate. Formate feeding in C. tropicalis triggered the accumulation of glycerol, ethanol and xylitol. Consequently, the specific xylose consumption increased 28% during formate feeding, from 477 to 609 C-mmol/C-mol cell dry-weight (CDW)/h. In C. guilliermondii cultures. formate feeding resulted only in glycerol accumulation. The specific xylose consumption increased 6%, from 301 to 319 C-mmol/C-mol CDW/h, until glycerol started to accumulate.


A randomized phase III study of radiotherapy alone or with 5-fluorouracil and mitomycin-C in patients with locally advanced adenocarcinoma of the pancreas: Eastern Cooperative Oncology Group study E8282.
The median survival time of patients with locally advanced adenocarcinoma of the pancreas is 8-10 months. Radiation therapy has been used to improve local control and palliate symptoms. This randomized study was undertaken to determine whether the addition of 5-fluorouracil (5-FU) and mitomycin-C (MMC) to radiation therapy improves outcome in this patient population. One hundred fourteen patients were randomized to receive 59.4 Gy external beam radiotherapy in 1.8 Gy fractions alone or in combination with 5-FU (1,000 mg/m2/day for 4 days by continuous infusion Days 2-5 and 28-31) and MMC (10 mg/m2 on Day 2). One hundred four patients were evaluable for efficacy. Hematologic and nonhematologic toxicities were more common in the combination arm. The response rates were 6% in the radiation therapy arm and 9% in the combination arm. There were no differences in median disease-free survival time (DFS) or overall survival time (OS) between the combination and radiation therapy alone arms: 5.1 vs. 5.0 months, respectively, for DFS (p = 0.19) and 8.4 vs. 7.1 months, respectively, for OS (p = 0.16). The addition of 5-FU and MMC to radiotherapy increased toxicity without improving DFS or OS in patients with locally advanced pancreatic cancer. Alternative drugs for radiosensitization may improve outcome.


Microsomal preparation from an animal tissue catalyzes release of carbon monoxide from a fatty aldehyde to generate an alkane.
Alkanes are widely distributed in nature and impaired alkane synthesis was implicated in certain neurological disorders. However, the mechanism of synthesis of alkanes in animals is unknown. Our search to find a convenient animal tissue to study alkane biosynthesis resulted in the finding that the uropygial gland (a modified sebaceous gland) of the eared grebe (Podiceps nigricollis) produces large amounts of alkanes. These alkanes, which constitute 35-41% of the total lipid produced, are mainly C21, C23, C25, and C27 n-alkanes. Cell free homogenates of this tissue synthesized alkanes from both fatty acid and aldehyde in the absence of O2. Differential centrifugation of the homogenates indicated that this activity was located in the microsomal fraction. With isolated microsomes conversion of fatty acid to alkane required CoA, ATP, and NADH whereas conversion of an aldehyde to alkane did not require the addition of cofactors. That the final step in alkane synthesis is a decarbonylation was shown by the stoichiometric production of heptadecane and CO from octadecanal. CO was identified by adsorption to RhCl [(C6H6)3P]3 and oxidation of the trapped CO to CO2 by watergas shift reaction. The enzyme preparation also catalyzed incorporation of 14C from 14CO into octadecanal showing the reversible nature of the decarbonylase. This decarbonylase had a sharp pH optimum at 7.0, a Kapp of 180 microM and a V1/2 of 90 rho mol/min/mg protein for octadecanal. The enzyme was inhibited by the metal chelators EDTA, O-phenanthroline, and 8-hydroxyquinoline, but not by KCN. It was stimulated nearly 3-fold by 5 microM 2-mercaptoethanol and inhibited by the presence of O2. During the conversion of [1-3H]octadecanal to heptadecane, 3H was lost to water and 3H from 3H2O was incorporated into the alkane generated from unlabeled octadecanal. The mechanism of the decarbonylation and the nature of the enzyme remain to be elucidated.


Aftercare in severe neurological impairment.
Modern neonatal intensive care has major emphasis on the resuscitation and management of infants born at the limits of viability. An additional significant group of infants are those, born at or close to term, who present with major neurological disease. This is a heterogeneous group of infants who have major care needs due to the continuing neurological abnormalities into the postneonatal period. Re-admissions to hospital are frequent and long-term developmental progress is poor. In this group of infants, there is a high early mortality. The recurrent admission of infants in this group for active resuscitation and/or intensive care may not always be the wisest management, and important medical, ethical and legal dilemmas are faced by families and carers of these infants.


Direct antimicrobial effects of chemokines on Cryptococcus spp, with special emphasis on a 'CXC' chemokine.
Cryptococcus species are ingenious human pathogens that are widespread globally. They continue to cause over 200,000 deaths per year. Presently due to the rise in resistance and therapy failure, it is necessary to shift the focus to an alternate therapeutic strategy against this pathogen. One promising approach is to emphasize the host defense system in order to develop more precise and customized treatment strategies. In this regard, research has revealed that interferon-γ-inducible CXCL10 chemokine, amongst other chemokines spanning both CXC and CC categories, has a direct killing effect in vitro against Cryptococcus neoformans and Cryptococcus gattii, with a significantly greater microbicidal effect against the former. Moreover, when CXCL10 is used in combination with CCL5, there is a significant reduction in the survival of C. gattii at normal-serum level concentration, indicating a previously unreported synergistic effect of these two chemokines. Confocal and STED microscopic studies have demonstrated that CXCL10 has both cell wall/membrane and intracellular targets against this fungus. These findings present new possibilities for developing chemokine-derived small molecule antifungals and may represent a step forward in creating precision medicine tailored to each patient.


TP53 mutations in prostatic cancer. Analysis of pre- and post-treatment archival formalin-fixed tumour tissue.
The TP53 gene mutation pattern in prostatic cancer was examined in relation to progression and survival, using archival formalin-fixed pre- and post-treatment tumour specimens from 84 prostatic cancer patients. Thirty-four had hormone-sensitive tumours and 50 were hormone-resistant. Six of the 34 (18 per cent) therapy-responding tumours and 19 of the 50 (38 per cent) hormone-resistant tumours showed p53 protein accumulation in the post-treatment specimen. Both pre- and post-treatment specimens from these 25 patients were analysed for mutation of the conserved regions of the TP53 gene (exons 5-8), using constant denaturant gel electrophoresis (CDGE) followed by DNA sequencing. In the post-treatment samples, mutations were detected in three of the six patients with hormone-responsive tumours and in 11 of the 19 patients with hormone-resistant tumours. The three (100 per cent) patients with therapy-responsive tumours with mutations and nine of the 11 (82 per cent) patients with therapy-resistant tumours with mutations died of the disease. Thirteen of the 14 mutations in the post-treatment specimens were transitions, 11 occurring at CpG dinucleotides in which codon 273 was involved in ten. A significantly higher proportion of tumours with mutations were poorly differentiated compared with tumours without mutation (P < 0.04). Our findings indicate that TP53 mutation is a late event in tumour development of the prostate gland and that codon 273 might be a 'hotspot' for mutation in the progression of the disease.


Investigation of activation cross sections of proton induced reactions on indium up to 70 MeV for practical applications.
Excitation functions were measured for production of the (113,111,110)Sn, (115m,114m,113m,112m,111g,110g)In and (111m,109)Cd radioisotopes by bombardment of In targets with proton beams up to 70 MeV, some of them for the first time. The new results are compared with the earlier experimental data and with the theoretical data in the TENDL-2014 (Talys1.6 based) library. Thick target yields were deduced and application of the new data for production of medically relevant (110m)In,(111g)In,(113m)In and (114m)In, as well as applicability for thin layer activation (TLA) are discussed.


Serial intravascular ultrasound comparison of the extent and distribution of intimal hyperplasia six months after stent implantation for de novo versus in-stent restenosis lesions.
The aim of this study was to compare intimal hyperplasia (IH) growth at 6 months in patients with de novo lesions treated with stents versus IH regrowth in patients with treated in-stent restenosis. Intravascular ultrasound was performed after intervention and at the 6-month follow-up visit as part of a standardized protocol across several clinical trials. At 6 months, the lumen was larger in the de novo group (mean lumen cross-sectional area [CSA] 6.31 +/- 2.2 vs 4.48 +/- 1.9 mm(2), p = 0.0001; minimum lumen CSA 4.2 +/- 1.8 vs 2.59 +/- 1.5 mm(2), p = 0.0001). However, the total increase in the mean IH CSA volume was the similar in the de novo and ISR groups (2.89 +/- 1.6 vs 2.64 +/- 1.94 mm(2), respectively; p = 0.11). We found that IH regrowth in restented in-stent restenosis lesions was similar to that in de novo stent implantation and that the final lumen CSA was an important component of in-stent restenosis recurrence.


New age patterns of survival improvement in Sweden: do they characterize changes in individual aging?
The parameters of the Gompertz approximation to the mortality curve are negatively correlated. Strehler and Mildvan [Science 132 (1960) 14] predicted this property of the mortality curve using a mathematical model of mortality and aging and then confirmed it in empirical studies. Despite the fact that their theory was based on the cohort model of mortality the SM correlation was also revealed in the analysis of period mortality data. In fact, most applications of the SM model to human data use Gompertz's approximation to the period mortality rate. Many researchers studying SM correlation consider it a universal demographic law. Such correlation prescribes a certain regularity in mortality changes. All mortality curves must intersect at one point. Mortality decline must produce the rectangularization of survival curves. In this paper we investigated the changes in the patterns of mortality decline in Sweden between 1861 and 1999. We found a difference in patterns of SM correlation for cohort and period mortality data. We investigated trends in survival improvement and found that the tendency to rectangularization of the survival curve existed for only a limited period of time. Then it was gradually replaced by near parallel shift of the survival curve to the right. We found that the pattern of SM correlation was relatively stable only at certain phases of the survival history of male and female populations. We analyzed past and recent patterns of survival changes and discussed possible causes for instability of SM correlation both in cohort and in period mortality data.


Evaluation of the factor structure of symptoms in patients with schizophrenia.
Considering the widespread use of the Positive and Negative Syndrome Scale (PANSS) and its factors around the world in clinical trials, it is clearly necessary to perform a transcultural validation of the factor structure of the PANSS. The purpose of the present study was to examine the PANSS factor structure in a Korean sample of subjects with schizophrenia. A total of 150 outpatients were assessed using the PANSS and other clinical rating scales. Principal component analyses revealed five factors, i.e., negative, cognitive/disorganization, positive, excitement, and depression/anxiety dimensions, which accounted for 64.1% of the total variance. All five factors showed good internal consistency, suggesting that the reliability of the factors extracted was adequate. Significant correlations were found between the five components of the PANSS and the corresponding clinical rating scales. The results of the present study indicate that the five-factor model best fit the data from our patients and that it was validated transculturally. The factor structures should be further validated using various neurobiological methods to ultimately help in clarifying the heterogeneity and pathogenesis of symptomatology in schizophrenia.


Facial vein aneurysm associated with sialadenitis.
A 20 year-old man presented with pain and swelling of the left submandibular area. Neck sonography revealed enlargement of the submandibular gland, coarsening of its echotexture with a few calculi and a multiloculated cystic lesion. Doppler sonography revealed venous flow within the cystic lesion and aneurysmal dilatation of the adjacent facial vein. CT angiography confirmed the facial vein aneurysm. We hypothesize that inflammation of the gland had weakened the wall of the adjacent facial vein, causing aneurysmal dilatation.


Circulating endothelial microparticles correlate inversely with endothelial function in patients with ischemic left ventricular dysfunction.
Bone-marrow derived endothelial progenitor cells (CD34+ and VEGFR2+ KDR+ EPC) and endothelial-derived microparticles (CD 31+Annexin V+, EMP; indicator for endothelial apoptosis) were examined in the peripheral blood of 35 male, clinically stable patients with 3-vessel coronary artery disease (CAD). The patients were divided in 2 groups, those with preserved or normal function (n = 17; EF 65 +/- 6%) and those with reduced left ventricular (LV) function (n = 18; EF 36 +/- 11%). The number of circulating EPCs was decreased by 25% (P = .07) and the number of EMPs was increased by 109 % (P < .05) in patients with LV dysfunction compared with those with normal or preserved LV function. EPCs were positively correlated (r = 0.24 for patients with LV dysfunction and r = 0.28 for patients with preserved LV function) with endothelial function as assessed by flow-mediated vasodilatation. In contrast, EMPs were inversely correlated (r = -0.42 for patients with LV dysfunction and r = -0.49 for patients with preserved LV function). CAD patients with significant LV dysfunction show an increased index of endothelial cell damage. This decrease (or lack of compensatory elevation) of EPCs may result in a reduced potential for repair and thus contribute at least in part to the pathogenesis of endothelial dysfunction.


Efficacy and safety of an intranasal virosomal respiratory syncytial virus vaccine adjuvanted with monophosphoryl lipid A in mice and cotton rats.
Respiratory syncytial virus infection remains a serious health problem, not only in infants but also in immunocompromised adults and the elderly. An effective and safe vaccine is not available due to several obstacles: non-replicating RSV vaccines may prime for excess Th2-type responses and enhanced respiratory disease (ERD) upon natural RSV infection of vaccine recipients. We previously found that inclusion of the Toll-like receptor 4 (TLR4) ligand monophosphoryl lipid A (MPLA) in reconstituted RSV membranes (virosomes) potentiates vaccine-induced immunity and skews immune responses toward a Th1-phenotype, without priming for ERD. As mucosal immunization is an attractive approach for induction of RSV-specific systemic and mucosal antibody responses and TLR ligands could potentiate such responses, we explored the efficacy and safety of RSV-MPLA virosomes administered intranasally (IN) to mice and cotton rats. In mice, we found that incorporation of MPLA in IN-administered RSV virosomes increased both systemic IgG and local secretory-IgA (S-IgA) antibody levels and resulted in significantly reduced lung viral titers upon live virus challenge. Also, RSV MPLA virosomes induced more Th1-skewed responses compared to responses induced by FI-RSV. Antibody responses and Th1/Th2-cytokine responses induced by RSV-MPLA virosomes were comparable to those induced by live RSV infection. By comparison, formalin-inactivated RSV (FI-RSV) induced serum IgG that inhibited viral shedding upon challenge, but also induced Th2-skewed responses. In cotton rats, similar effects of incorporation of MPLA in virosomes were observed with respect to induction of systemic antibodies and inhibition of lung viral shedding upon challenge, but mucosal sS-IgA responses were only moderately enhanced. Importantly, IN immunization with RSV-MPLA virosomes, like live virus infection, did not lead to any signs of ERD upon live virus challenge of vaccinated animals, whereas IM immunization with FI-RSV did induce severe lung immunopathology under otherwise comparable conditions. Taken together, these data show that mucosally administered RSV-MPLA virosomes hold promise for a safe and effective vaccine against RSV.


Chromosomal analysis of bladder cancer. II. A practical method.
Twenty-seven successive bladder cancer tissue specimens, varying from noninfiltrating to deeply infiltrating ones, were chromosomally analyzed using a new direct method. Recognizable metaphases were obtained from 25 specimens (93%). In nearly all cases, suitable C-banding and in nine cases G-banding was achieved. Essential steps in this method are colcemid application in two steps, interrupted by washing with Hanks' balanced sodium solution and two separated hypotonic treatments. This method is easy to use and not time consuming.


[Post-hospital rehabilitation center of a psychiatric hospital (clinical, organizational and economic aspects)].
The authors generalize a 3.5th year experience of postclinical rehabilitation of mental patients with unfavourable forms of the disease and significant psychic defects in a special rehabilitative center which functions on the basis of an agricultural enterprise (a state farm). The organizational and methodological principles of post-clinical rehabilitation are given. On the basis of the examinations of 88 patients the authors analyse the results of their rehabilitation in the clinical, working and social aspects. The economic effectiveness of the rehabilitative center activity and its influence on the level of psychiatric service organization is evaluated.


Extra-long treatment of MDR-TB osteomyelitis of humerus due to neurotoxicity from the 2nd-line drugs: a case report.
Infection with tuberculosis (TB) still considered a leading infectious cause of death, osteomyelitis TB rare entity, and being extraspinal MDR-TB make it very rare case; most of experience in treating osteomyelitis TB was derived from pulmonary TB experience, and we present a case of humerus MDR-TB that was treated for 5 years, with several interruption due to side effect and other causes.


The novel HLA-B allele, HLA-B*50:31, was identified by sequencing genomic DNA.
The novel HLA-B allele, HLA-B*50:31, was identified by sequencing genomic DNA.


Objectively measured association between air pollution and physical activity, sedentary behavior in college students in Beijing.
The purpose of this study is to examine the association between hourly air pollution on hourly physical activity (PA) and sedentary behavior (SB) among college students in Beijing, China. The secondary aim was to examine such associations varied at specific time. A total of 340 participants were recruited from the Tsinghua University, in Beijing, China. Accelerometers provided PA measures, including moderate-to-vigorous physical activity (MVPA), walking steps, energy expenditure and sedentary time for 7 consecutive days. Corresponding air pollution data by the Beijing Municipal Ecological Environment Bureau in the closed site (Wan Liu site) in Tsinghua University were collected including average hourly air quality index (AQI) and PM2.5 (μg/m³). Associations were estimated using linear individual fixed-effect regressions. We also conducted an air pollution risk perception survey among 2307 freshmen (76.6% males) who were enrolled in Tsinghua in 2016, and the survey was done in May 22-26, 2017. A one level increase in hourly air quality index (AQI) was associated with a reduction in 1-h PA by 0.083 (95% confidence interval [CI] = -0.137, -0.029) minutes of MVPA, 8.8 (95% CI = -15.0, -2.6) walking steps, 0.65 (95% CI = -1.03, -0.27) kcals of energy expenditure. A 10 μg/m³ increase in air pollution concentration in hourly PM2.5 was associated with a reduction in 1-h PA by 0.021 (95% confidence interval [CI] = -0.033, -0.010) minutes of MVPA, 2.2 (95% CI = -3.5, -0.9) walking steps, 0.170 (95% CI = -0.250, -0.089) kcals of energy expenditure an increase in 1-h sedentary behavior 0.045 (0.005, 0.0845). At specific time, stronger negative associations of AQI and PM2.5 air pollution with PA at 8 a.m., 4 p.m., 5 p.m. and 7 p.m. Similarly, stronger positive associations of 1 h AQI and PM2.5 air pollution with SB at 8 a.m., 9 a.m., 11 a.m., and 7 p.m. A total of 94.9% participants (n = 2235) responded "yes" to air pollution change activities in the survey, which may partially explain PA change. Air pollution may discourage physical activity and increases sedentary behavior among freshman students living in Beijing, China. This is preliminary study. The impact of air pollution on physical activity and sedentary behavior at a specific time may be different.


Handgrip strength-a risk indicator for future fractures in the general population: findings from a prospective study and meta-analysis of 19 prospective cohort studies.
Evolving debate suggests that handgrip strength, a measure of muscular strength, might be associated with the risk of fractures; however, the evidence is conflicting. We aimed to assess the association of handgrip strength with the risk of fracture in the general population. Handgrip strength, measured using a dynamometer, was assessed at baseline in a population-based sample of 853 men and women aged 61-73 years in the Kuopio Ischemic Heart Disease prospective cohort. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated for incident fractures. Incident fractures (hip, humeral, or wrist) (n = 159) occurred during a median follow-up of 16.7 years. Comparing extreme tertiles of handgrip strength, the age- and sex-adjusted hazard ratio (95% CI) for fractures was 0.80 (0.55-1.18). The association remained similar on further adjustment for other potential confounders: HR (95% CI) of 0.82 (0.55-1.21). In a meta-analysis of 19 population-based prospective cohort studies (including the current study) comprising 220,757 participants and 9199 fractures (including 1302 hip fractures), the fully adjusted relative risk (RR) (95% confidence interval, CI) for incident fractures was 0.70 (0.61-0.80) comparing the top versus bottom thirds of handgrip strength. The association remained significant after trim-and-fill correction for publication bias. The corresponding RR (95% CI) for hip fractures (9 studies) was 0.61 (0.54-0.70). Handgrip was only modestly associated with fracture risk in the primary analysis, which may be driven by the low event rate. Pooled prospective cohort evidence suggests that elevated handgrip strength is associated with reduced future fracture risk.


Paraneoplastic chorea with leukoencephalopathy presenting with obsessive-compulsive and behavioral disorder.
Chorea is a rare manifestation of paraneoplastic disease and is associated with CV2/CRMP-5 antibodies. Obsessive-compulsive disorder and large-scale white matter abnormalities on MRI have not been previously reported in association with these antibodies. We report on a case of CV2 paraneoplastic syndrome with obsessive-compulsive behavior preceding the motor manifestations of chorea with associated leukoencephalopathy on MRI. The literature on paraneoplastic chorea is reviewed.


Low humoral responses to hepatitis C virus among pediatric renal transplant recipients.
Immunosuppressed patients infected with hepatitis C virus (HCV) are known to have a low prevalence of antibodies to the virus. We examined 12 HCV-infected renal transplant recipients and 18 immunocompetent patients in terms of viral markers. The renal patients had a lower prevalence of anti-C100-3 antibodies and lower titers of anti-p22 than the immunocompetents. Low titers of the antibodies seemed to be characteristic of HCV, because titers of anti-mumps and anti-cytomegalovirus antibodies were the same or even increased. Quantitation of HCV RNA showed approximately 200-fold more copies of mean HCV RNA in the sera of the kidney patients than in the immunocompetents. This indicates that the low humoral responsiveness to HCV is not due to the lower concentration of the virus. Immunosuppressive conditions seemed to suppress anti-HCV production with greater magnitude than other viral antibodies.


Antimicrobial activity of Pycnogenol.
Pycnogenol, a standardized extract of Pinus pinaster bark, was tested for its antimicrobial activity against 23 different pathogenic prokaryotic (gram-positive and gram-negative) and eukaryotic (yeast and fungi) microorganisms. Pycnogenol inhibited the growth of all the tested microorganisms in minimum concentrations ranging from 20 to 250 microg/mL. Thus, Pycnogenol in concentrations as low as 0.025% could counteract the growth of all the strains investigated in our study. These results conform with clinical oral health care studies describing the prevention of plaque formation and the clearance of candidiasis by Pycnogenol.


Anterior cruciate ligament bundle measurement by MRI.
An accurate in vivo method of measuring dimensions of the anteromedial (AM) and posterolateral (PL) anterior cruciate ligament (ACL) bundles has not been established. The purpose of this study was to measure each individual bundle using double oblique axial MR imaging of the ACL, to compare this with cadaveric measurements, and to investigate the range of measurements seen in normal subjects. In five cadaveric knees, measurements obtained of the proximal, middle, and distal segments of each ACL bundle from double oblique axial MR images were compared with direct measurements following anatomical dissection. Thereafter, the size of both bundles from 24 normal knees was measured using an identical MR technique. Inter-observer variation was calculated using intraclass correlation. ACL bundle measurement in the cadaveric knees had a strong correlation (r = 0.93) with measurements obtained following anatomical dissection. No significant difference existed between measurements obtained from cadaveric knees and living normal subjects (p > 0.05). Interobserver correlation for MR measurements was excellent (R = 0.92-0.93). Overall, the long and short axis of the AM bundle were significantly larger than those of the PL bundle (p < 0.05). Also, men showed significantly larger AM and PL bundles than women (p < 0.05). Bundle size was not related to age or knee dominance. The individual ACL bundles can be accurately measured on double oblique axial MR imaging. The AM bundle is larger in caliber than the PL bundle. Both bundles are larger in men than in women and there is no significant side-to side difference.


The combination of antihistamine (chlorpheniramine) and an omega-3/omega-6 fatty acid-containing product for the management of pruritic cats: results of an open clinical trial.
Chlorpheniramine maleate (2 mg/cat every 12 h orally) and a fatty acid supplement (0.5 ml/cat every 24 h orally) were administered in combination to 11 pruritic cats. Although none of the cats had responded to the two products when they were administered as single therapeutic agents, six of the cats (54%) had an excellent response to the combination. Adverse effects were not seen. Under the conditions of this study, the combination of antihistamine (chlorpheniramine) and the omega-3/omega-6 fatty acid-containing supplement exhibited a superior antipruritic effect to either product alone.


Comparison of the effect of althesin with diazepam and thiopental sodium on cortical and subcortical epileptic activity in the rat.
Althesin antiparoxysmal effect was comparatively studied with diazepam and thiopental sodium on penicillin induced cortical epileptic focus and on mesencephalic reticular unitary activity triggered by cortical spikes. Althesin was shown to abolish both cortical and subcortical epileptic activity, while diazepam was able to suppress the paroxysmal unitary activity evoked from the cortical spikes at the level of the reticular mesencephalic formation, but was ineffective on focal paroxysm. Thiopental sodium exhibited behaviour similar to Althesin, but its action was weak and short lasting at both levels. A comparative study showed that Althesin had, at cortical and subcortical level, a more drastic and longer antiparoxysmal effect than the other two drugs tested. Althesin would seem to exert a potent antiepileptic effect through a double action: i) it suppresses abnormal activity at cortical focus level ii) it depresses the multineural mechanism involved in the seizure spread at subcortical level.


Effect of COVID-19 on sexual and reproductive functions of Egyptian males following recovery: A cross sectional study.
We aimed to assess the sexual and the reproductive functions in males post COVID-19 infection in Beni-Suef Governorate. One hundred men were recruited in the current study. All participants were assessed by the Arabic validated version of the International Index of the Erectile Function 5 (ArIIEF-5), semen analysis, and Hospital Depression and Anxiety Scale (HADS). Finally, morning testosterone serum level was measured. There were significant decreases in the sperm total motility, the ArIIEF-5 score, and serum total testosterone in the post COVID-19 patients after 3 months when compared to the controls. However, there were significant increases in the sperm total motility, the ArIIEF-5 score, and serum total testosterone in the post COVID-19 patients after 6 months group when compared to the post COVID-19 patients after 3 months group. Moreover, there was a significant increase in the HADS score in the post COVID-19 patients after 3 months when compared to the controls. In contrast, there was a significant decrease in the HADS score in the post COVID-19 patients after 6 months when compared to the post COVID-19 patients after 3 months. Our study had shown temporary impairment of sexual and reproductive functions in post COVID-19 convalescent males especially after 6 months from the onset of the infection.


Coupling effects of mineral components on arsenic transformation during coal combustion.
Exploring arsenic (As) transformation during coal combustion is beneficial for reducing its pollution. Herein, combustion experiments were developed at 1100-1300 °C in a fixed-bed experimental system with 25 types of coal samples. The occurrences of As in coal and combustion products were characterized. All the original forms of As in coal were found to be unstable during combustion. As retained in ash existed as water-soluble and ion-exchangeable and residual forms, but only as residual form at combustion temperature above 1200 °C. The distribution of As in gaseous and solid combustion products varied widely by coal types, which resulted from the coupling effects of multi-minerals in coal. Co-combustion experiments were conducted using As model compounds and pure minerals, by which the interaction of Ca, Fe, Si and Al minerals to retain As was elucidated. The As transformation during coal combustion was primarily attributed to the coupling action of Ca, Fe, Si and Al minerals in coal. As a result, As was retained as Ca-Si-Al-As and Fe-Si-Al-As composite salts in the ash, which have little environmental hazard. Utilizing the coupling effects of multi-minerals during combustion help reduce As pollution from coal-fired plants.


Influence of peers and friends on overweight/obese youths' physical activity.
This review offers a theoretical framework to account for the effects of peers on youths' physical activity. Our research indicates the following: 1) that the youth are more physically active in the presence of friends and peers than in the presence of family members or when alone, 2) peers and friends increase overweight/obese youths' motivation to be physically active, 3) peers' weight status does not moderate the effect of peers on youths' physical activity, and 4) experiencing negative peer interaction, such as ostracism, decreases physical activity in youth. We propose that the consideration of the peer social context as a contributor to physical (in)activity and maintenance of overweight status may further our understanding of physical and behavioral health trajectories and improve prevention and intervention efforts.


Propranolol ameliorates retinopathy of prematurity in mice by downregulating HIF-1α via the PI3K/Akt/ERK pathway.
Retinopathy of prematurity (ROP) is the leading cause of blindness in infants, and elevation of HIF-1α through the PI3K/Akt and ERK pathways is implicated in ROP pathogenesis. The mechanism of action of propranolol in ROP remains controversial. We investigated the effect of propranolol on ROP and explored its potential mechanisms of action in an oxygen-induced retinopathy (OIR) mouse model. OIR mice were first treated with propranolol intraperitoneally, and the retina integrity was measured by FITC-dextran and hematoxylin-eosin staining. The expression of HIF-1α, VEGF, and key signaling pathway proteins was determined using real-time PCR and western blotting. FITC-dextran staining showed that propranolol treatment reduced damage to retinal morphology in OIR mice. Mice treated with propranolol showed a reduced number of nuclei of vascular endothelial cells penetrating the inner limiting membrane of the retina, confirming the therapeutic effect of propranolol on ROP. Further analysis showed that HIF-1α and PI3K/Akt/ERK pathway protein levels were significantly elevated in OIR mice. In contrast, propranolol treatment downregulated the expression of these proteins, indicating that the PI3K/Akt/ERK/HIF-1α axis is associated with propranolol-induced ROP alleviation. Propranolol has a therapeutic function against ROP, likely through the downregulation of HIF-1α via the PI3K/Akt/ERK pathway. Propranolol can reduce the formation of abnormal retinal neovascularization in oxygen-induced retinopathy (OIR) models, and reduce leaking, tortuous, and abnormally expanding retinal blood vessels. Propranolol possibly improves OIR by inhibiting the activated ERK and HIF-1α pathways. Furthermore, propranolol may downregulate HIF-1α via the PI3K/Akt/ERK pathway to ameliorate retinopathy of prematurity. This study elucidated that the therapeutic effect of propranolol in OIR mice does not involve the VEGFR-2 pathway.


Resonance Raman spectroscopy can detect structural changes in haemozoin (malaria pigment) following incubation with chloroquine in infected erythrocytes.
Resonance Raman spectroscopy was applied to monitor the effects of chloroquine (CQ) treatment on cultures of Plasmodium falciparum trophozoites. A number of bands assigned to A(1g) and B(1g) modes characteristic of the haemozoin aggregate are reduced in intensity in the CQ-treated cells, however, no bands from the CQ are observed. The intensity changes are attributed to intermolecular drug binding of the CQ in a sandwich type complex between ferriprotoporphyrin IX (FePPIX) dimer units. It is postulated that the CQ binds via pi-pi interactions between adjacent and orientated porphyrins thereby disrupting the haemozoin aggregate and reducing excitonic interactions between adjacent haems. The results show the potential of Raman microscopy as a screening tool for FePPIX:drug interactions in live cells.


Sound Classification and Call Discrimination Are Decoded in Order as Revealed by Event-Related Potential Components in Frogs.
Species that use communication sounds to coordinate social and reproductive behavior must be able to distinguish vocalizations from nonvocal sounds as well as to identify individual vocalization types. In this study we sought to identify the neural localization of the processes involved and the temporal order in which they occur in an anuran species, the music frog Babina daunchina. To do this we measured telencephalic and mesencephalic event-related potentials (ERPs) elicited by synthesized white noise (WN), highly sexually attractive (HSA) calls produced by males from inside nests and male calls of low sexual attractiveness (LSA) produced outside of nests. Each stimulus possessed similar temporal structures. The results showed the following: (1) the amplitudes of the first negative ERP component (N1) at ∼ 100 ms differed significantly between WN and conspecific calls but not between HSA and LSA calls, indicating that discrimination between conspecific calls and nonvocal sounds occurs in ∼ 100 ms, (2) the amplitudes of the second positive ERP component (P2) at ∼ 200 ms in the difference waves between HSA calls and WN were significantly higher than between LSA calls and WN in the right telencephalon, implying that call characteristic identification occurs in ∼ 200 ms and (3) WN evoked a larger third positive ERP component (P3) at ∼ 300 ms than conspecific calls, suggesting the frogs had classified the conspecific calls into one category and perceived WN as novel. Thus, both the detection of sounds and the identification of call characteristics are accomplished quickly in a specific temporal order, as reflected by ERP components. In addition, the most dynamic ERP patterns appeared in the left mesencephalon and the right telencephalon, indicating the two brain regions might play key roles in anuran vocal communication.


Changes in apoptosis-related protein (p53, Bax, Bcl-2 and Fos) expression with DNA fragmentation in the central nervous system in rats after closed head injury.
This study aimed to examine the temporal profile of neuronal apoptosis in the central nervous system (CNS) following closed head injury in rat. Fos immunoreactivity was detected in neuronal nuclei in the cerebral cortex at 2 h after head injury. At 4 h, Bax protein expression was elevated with a concomitant down-regulation of Bcl-2 expression. Along with this, a marked immunoexpression of p53 was also observed in these cells. Double immunolabelling study has shown the colocalization of Bax immunoreactivity with Bcl-2 and p53. In rats killed 1 day after injury, a variable number of transferase d-UTP nick-end labelling positive cells were observed. Present findings suggest that the upregulation of p53 and a shift in the ratio of Bcl-2 to Bax may contribute to neuronal apoptosis in the CNS after closed head injury.


Unveiling Charge Carrier Recombination, Extraction, and Hot-Carrier Dynamics in Indium Incorporated Highly Efficient and Stable Perovskite Solar Cells.
Perovskite solar cells (PSCs) have been propelled into the limelight over the past decade due to the rapid-growing power conversion efficiency (PCE). However, the internal defects and the interfacial energy level mismatch are detrimental to the device performance and stability. In this study, it is demonstrated that a small amount of indium (In3+ ) ions in mixed cation and halide perovskites can effectively passivate the defects, improve the energy-level alignment, and reduce the exciton binding energy. Additionally, it is confirmed that In3+ ions can significantly elevate the initial carrier temperature, slow down the hot-carrier cooling rate, and reduce the heat loss before carrier extraction. The device with 1.5% of incorporated In3+ achieves a PCE of 22.4% with a negligible hysteresis, which is significantly higher than that of undoped PSCs (20.3%). In addition, the unencapsulated PSCs achieve long-term stability, which retain 85% of the original PCE after 3,000 h of aging in dry air. The obtained results demonstrate and promote the development of practical, highly efficient, and stable hot-carrier-enhanced PSCs.


Serum free light-chain responses after high-dose intravenous melphalan and autologous stem cell transplantation for AL (primary) amyloidosis.
Serum free light-chain (FLC) concentrations were measured by a sensitive nephelometric immunoassay in 66 patients with AL amyloidosis before and after treatment with high-dose melphalan and autologous stem cell transplantation (HDM/SCT). At 1 year after HDM/SCT, 27 patients (41%) achieved a complete hematologic response (CR), that is, disappearance of the monoclonal gammopathy previously evident by immunofixation electrophoresis (IFE) in serum and urine and of plasma cell clonality in the bone marrow. Abnormally elevated FLC levels became normal in 27 patients (41%), and decreased by >90% in 37 (56%). Average improvements in FLC were 94% for patients who achieved a CR and 72% for those who did not (P=0.0001). However, a reduction in FLC of >90% was associated with a similar high likelihood of clinical improvement and prolonged survival, whether or not patients achieved a CR. While CR, as defined by standard criteria, is a more stringent indicator of hematologic response than are decreases in abnormally elevated FLC levels per se, these measures of hematologic response are complementary, and decreases in FLC are more readily detected early after treatment than are the changes in IFE and marrow studies required to determine CR.


Primary structure of the oligosaccharide determinant of blood group Cad specificity.
Glycophorin A and B from Cad erythrocyte membranes are the carriers of the blood group Cad determinants. They are characterized by a significant increase in molecular mass, as compared to the corresponding glycophorins from control erythrocytes (Cartron, J.-P., and Blanchard, D. (1982) Biochem. J. 207, 497-504). Lipid-free glycophorin A, purified from Cad red cells, showed an increased GalNAc content in comparison to blood group B, Cad-negative, control cells. Alkaline-borohydride treatment of this Cad glycophorin A released as a predominant species a pentasaccharide; its structure was determined, by methylation analysis and by 500-MHz 1H-NMR studies, to be: (formula; see text) This novel oligosaccharide inhibited strongly the hemagglutination of Cad erythrocytes by the Dolichos biflorus lectin. It shares with the blood group Sda determinant a terminal GalNAc beta (1 leads to 4)Gal beta (1 leads to .) sequence.


Presence of a consensus DNA motif at nearby DNA sequence of the mutation susceptible CG nucleotides.
Complexity in tissues affected by cancer arises from somatic mutations and epigenetic modifications in the genome. The mutation susceptible hotspots present within the genome indicate a non-random nature and/or a position specific selection of mutation. An association exists between the occurrence of mutations and epigenetic DNA methylation. This study is primarily aimed at determining mutation status, and identifying a signature for predicting mutation prone zones of tumor suppressor (TS) genes. Nearby sequences from the top five positions having a higher mutation frequency in each gene of 42 TS genes were selected from a cosmic database and were considered as mutation prone zones. The conserved motifs present in the mutation prone DNA fragments were identified. Molecular docking studies were done to determine putative interactions between the identified conserved motifs and enzyme methyltransferase DNMT1. Collective analysis of 42 TS genes found GC as the most commonly replaced and AT as the most commonly formed residues after mutation. Analysis of the top 5 mutated positions of each gene (210 DNA segments for 42 TS genes) identified that CG nucleotides of the amino acid codons (e.g., Arginine) are most susceptible to mutation, and found a consensus DNA "T/AGC/GAGGA/TG" sequence present in these mutation prone DNA segments. Similar to TS genes, analysis of 54 oncogenes not only found CG nucleotides of the amino acid Arg as the most susceptible to mutation, but also identified the presence of similar consensus DNA motifs in the mutation prone DNA fragments (270 DNA segments for 54 oncogenes) of oncogenes. Docking studies depicted that, upon binding of DNMT1 methylates to this consensus DNA motif (C residues of CpG islands), mutation was likely to occur. Thus, this study proposes that DNMT1 mediated methylation in chromosomal DNA may decrease if a foreign DNA segment containing this consensus sequence along with CG nucleotides is exogenously introduced to dividing cancer cells.


A Systematic Review of Rehabilitation for Corticobulbar Symptoms in Adults with Huntington's Disease.
Corticobulbar symptoms have been reported in all stages of Huntington's disease (HD); aspiration pneumonia associated with swallowing impairment has been identified as the most common cause of death. Whilst recent research has described positive effects of corticobulbar rehabilitation in other neurodegenerative conditions, it is unclear if this is similarly effective in HD. Preliminary evidence in corticospinal rehabilitation has revealed physical therapy and exercise could be beneficial for individuals with HD. This systematic review will explore the literature relative to rehabilitation of corticobulbar symptoms in adults with HD. Two investigators independently searched relevant electronic databases for literature related to corticobulbar rehabilitation in HD, published in English until October 2019. Included studies were critically appraised using the Oxford Centre for Evidence-based Medicine Levels of Evidence, Cochrane Risk of Bias Tool and Scottish Intercollegiate Guidelines Network checklists. Study outcomes included measurements of function, quality of life or neuromuscular physiology. Seventy-seven publications were screened with eight studies meeting the inclusion criteria - two randomised control trials and six intervention studies. Validated and objective outcome measures of corticobulbar symptoms were infrequently used. There was a high risk of bias identified in 7/8 studies. The data suggested positive clinical outcomes, no adverse effects and no deterioration observed across longitudinal studies. This systematic review documented a lack of high-quality evidence to support the use of rehabilitation to treat corticobulbar symptoms in HD. However, the suggestion of potential positive effects based on available, albeit limited, studies provides justification for further research in this area.


Immunoblot identification of 13.5 kilodalton myelin basic protein in goldfish brain myelin.
Myelin isolated from goldfish brain shows a multilamellar structure with a major dense line and two intraperiod lines. Sodium dodecyl sulfate gel electrophoresis revealed that the protein profile of goldfish brain myelin is distinctly different from that of rat brain myelin. No protein migrating to the position of proteolipid protein or DM-20 was seen in goldfish myelin. Goldfish acclimated to 5 degrees, 15 degrees, and 30 degrees C showed no qualitative differences in myelin proteins. The 13.5 kD protein in goldfish brain myelin and brain homogenate was intensely immunostained with the antiserum to human basic protein by the immunoblot technique. In contrast, none of the proteins of goldfish myelin were immunostained with antiproteolipid protein serum; however, both proteolipid protein and DM-20 of rat brain myelin were immunostained. The significance of the synthesis of myelin proteins by astrocytes in the goldfish brain is discussed.


Massive presence of Echinococcus granulosus (Cestoda, Taeniidae) cysts in a wild boar (Sus scrofa) from Spain.
We report a heavy infestation of a free-living wild boar sow from Spain with Echinococcus granulosus cysts and state its molecular characterization. We found >65 hydatid cysts in the thoracic and abdominal cavities of the sow. Parasites were routinely processed for their identification and histopathology and DNA molecular characterization of the E. granulosus cysts were carried out. The polymerase chain reaction results confirmed the E. granulosus identity of the cysts and restriction fragment length polymorphism and sequencing revealed its G1 genotype. Our results suggest that wild boar could be involved in the epidemiology of E. granulosus, particularly considering that large amounts of carcass remains are available to dogs and wolves during the hunting season. The recent population increase of the wild boar in Spain and the DNA confirmation that the wild boar isolate shared identical sequences to the sheep strain emphasize the importance of the reported finding in public health.


Severity and Predictors of Outcome of Motorcycle-Associated Head Injury: An Experience from a Regional Neurosurgery Centre in Northern Nigeria.
Motorcycle-associated head injury is one of the leading causes of disability and deaths, with its main victims being the motorcyclists, passengers, and pedestrians in their young productive age group. This study determines the role of severity and some predictive factors on survival and mortality of motorcycle-associated head injury. This is a cross-sectional study using data of patients managed for motorcycle-associated head injuries between December 2014 and November 2016. The patients' biodata, clinical findings, and management outcomes were analyzed using Statistical Packages for the Social Sciences version 20. A total of 184 patients were analyzed, most of whom (81%) were aged ≤40 years and with a male dominance of 6.7:1. Pupillary abnormality was seen in 43.5% of the patients, and severe head injury occurred in 34.2% of the patients. Hemorrhagic contusion was the most common computed tomography (CT) finding (16.3%). Among 20.8% of the patients who died, 63.2% had severe head injury. Motorcycle-associated head injury predominantly occurred among young men who used a motorcycle for commercial purposes. The survival rate was higher among patients who had brain CT scan performed, extra-axial clots, and operative treatment. However, high mortality was seen among patients who could not afford brain CT scan, and who had bilateral pupillary dilatation, CT findings of abnormalities that are not surgically amenable, and severe head injury.


Esophageal dilation with integrated balloon imaging: initial evaluation in a porcine model.
When treating achalasia, balloon dilation is often combined with fluoroscopy to allow the lower esophageal sphincter to be visualized as it is being dilated. We sought to evaluate a new balloon dilation technology, EsoFLIP, which allows the shape of the balloon to be visualized in a nonradiographic manner by using impedance planimetry electrodes located within the dilation balloon. Two pigs weighing 35 kg were used. The EsoFLIP balloon dilator was introduced under endoscopic visualization. Successive injections of 50, 60, 70 and 85 mL into the dilation balloon permitted dilations at increasing diameters to be achieved. Following each dilation fluid was withdrawn to leave 30 mL in the balloon and an EsoFLIP image was captured to track progressive dilation of the gastroesophageal junction (GEJ). The EsoFLIP catheter was safely deployed in the two pigs and no complications were noted. For pig 1, during dilation, the measured balloon diameter at the waist was 24.1, 28.9, 29.2 and 30.0 mm for balloon dilation volumes of 50, 60, 70 and 85 mL respectively. For pig 2 the corresponding diameter at the waist was 22.8, 27.1, 28.5 and 29.4 mm. The GEJ diameter increased from 12.5 and 12.4 mm to 17.4 and 17.5mm for pigs 1 and 2 respectively. Distensibility of the GEJ in pig 1 increased from 2.3 mm(2)/mmHg before to 4.4 mm(2)/mmHg after dilation and in pig 2 from 4.4 to 9.6 mm(2)/mmHg. The GEJ substantively achieved its final diameter after the dilation using just 50 mL in the balloon. We demonstrated technical feasibility and safety of the EsoFLIP dilator in a porcine model. Further studies in humans with achalasia remain to be conducted, which, besides demonstrating technical feasibility, should also evaluate the use of distensibility measurements taken during dilation to predict outcomes.


Respiration-deficient Chinese hamster cell mutants: genetic characterization.
We present here genetic experiments with a series of Chinese hamster cell mutants defective in oxidative energy metabolism. The mutations were all shown to be recessive in intraspecies hybrids. Thirty-five mutants were sorted into eight complementation groups, but one of these mutants failed to complement representatives of two distinct complementation groups. The possibility was raised that this is a cell carrying two mutations or a deletion. Because of the greatly different frequencies with which such mutants could be isolated from two different Chinese hamster cell lines, CCL16 (DON) and V79, the stability of representatives from each cell line was examined, and it was found that revertants could be obtained after treatment with mutagens, while spontaneous revertants appeared at unmeasurable or extremely low frequencies, with one exception. The mutant with a very noticeable frequency of spontaneous reversion was defective in mitochondrial protein synthesis, and the question arose whether the mutation was on the mitochondrial genome. A detailed fluctuation analysis of reversion rate and comparison with rates for other mutations was consistent with a nuclear mutation. This conclusion was supported by experiments involving fusions with cytoplasts.