The protective influence of parents and peers in violence avoidance among African-American youth.
This study attempted to provide further insight into the roles of parents and peers as they influence youth involvement with violence. Specifically, this paper considers whether parents who are close to their children have children who affiliate with prosocial friends who may in turn serve as a buffer against violence. This study also considers how parent and peer influences may change as youth transition to adolescence. A cross-sectional health behavior survey was administered to 384 low-income, African-American youth aged 10-15 from three Chicago area schools. Structural equation models (SEM) were developed to assess the impact of youth reported prosocial friends and parental closeness on violence involvement. The overall model was tested to examine equivalence across preadolescent and adolescent age-groupings. Results from the overall model indicated that parental closeness did not have a direct influence on youth violence involvement, but having a close parent-child relationship improved the youth's ability to select prosocial friends, which was directly related to decreased involvement with violence. Differences in the model by age-grouping suggested the presence of prosocial friends was a stronger factor for adolescent violence avoidance when compared to preadolescents. Parents can make a difference in the way in which their children choose their friends and therefore get involved with violence by maintaining a closely bonded relationship throughout preadolescence and adolescence. The importance of this closely bonded relationship has even greater effects for decreasing violence involvement for adolescents than preadolescents.


A comprehensive analysis of single-cell RNA transcriptome reveals unique SPP1+ chondrocytes in human osteoarthritis.
Osteoarthritis (OA) has become the most common degenerative disease in the world, which brings a serious economic burden to society and the country. Although epidemiological studies have shown that the occurrence of osteoarthritis is associated with obesity, sex, and trauma, the biomolecular mechanisms for the development and progression of osteoarthritis remain ambiguous. Several studies have drawn a connection between SPP1 and osteoarthritis. SPP1 was first found to be highly expressed in osteoarthritic cartilage, and later more studies have shown that SPP1 is also highly expressed in subchondral bone and synovial in OA patients. However, the biological function of SPP1 remains unclear. Single-cell RNA sequencing (scRNA-seq) is a novel technique that reflects gene expression at the cellular level, making it better depict the state of different cells than ordinary transcriptome data. However, most of the existing chondrocyte scRNA-seq studies focus on the occurrence and development of OA chondrocytes and lack analysis of normal chondrocyte development. Therefore, to better understand the mechanism of OA, scRNA-seq analysis of a larger cell volume containing normal and osteoarthritic cartilage is of great importance. Our study identifies a unique cluster of chondrocytes characterized by high SPP1 expression. The metabolic and biological characteristics of these clusters were further investigated. Besides, in animal models, we found that the expression of SPP1 is spatially heterogeneous in cartilage. Overall, our work provides novel insight into the potential role of SPP1 in OA, which sheds light on understanding the role of SPP1 in OA, promoting the progress of the treatment and prevention in the field of OA.


The US regulatory and pharmacopeia response to the global heparin contamination crisis.
The contamination of the widely used lifesaving anticoagulant drug heparin in 2007 has drawn renewed attention to the challenges that are associated with the characterization, quality control and standardization of complex biological medicines from natural sources. Heparin is a linear, highly sulfated polysaccharide consisting of alternating glucosamine and uronic acid monosaccharide residues. Heparin has been used successfully as an injectable antithrombotic medicine since the 1930s, and its isolation from animal sources (primarily porcine intestine) as well as its manufacturing processes have not changed substantially since its introduction. The 2007 heparin contamination crisis resulted in several deaths in the United States and hundreds of adverse reactions worldwide, revealing the vulnerability of a complex global supply chain to sophisticated adulteration. This Perspective discusses how the US Food and Drug Administration (FDA), the United States Pharmacopeial Convention (USP) and international stakeholders collaborated to redefine quality expectations for heparin, thus making an important natural product better controlled and less susceptible to economically motivated adulteration.


Hepatic drug conjugation/deconjugation systems in hepatosplenic schistosomiasis.
The biotransformation capacity of the liver is altered in hepatosplenic schistosomiasis being more in favor of deconjugation pathways. These alterations should be considered when xenobiotics are administered and in studies of hepatic toxicity and carcinogenicity.


Incomplete synthesis of the Sda/Cad blood group carbohydrate in gastrointestinal cancer.
Cancer-associated changes in cell surface carbohydrates, including incomplete synthesis of normal carbohydrate epitopes, strongly affect malignant and metastatic potential. Here, we report that compensating for the cancer-associated loss of a single glycosyltransferase, beta1,4N-acetylgalactosaminyltransferase T2, dramatically decreased cell surface expression of both E-selectin ligands (sialyl Lewis(x) and sialyl Lewis(a)). This modification was associated with elevated expression of the Sd(a) carbohydrate determinant, which is expressed in normal gastrointestinal mucosa and is strikingly downregulated in cancer tissues. Loss of E-selectin ligands resulted in decreased adhesion of cancer cells to activated human endothelial cells in vitro and eventually suppressed metastatic potential in vivo.


Structure of the K82 Capsular Polysaccharide from Acinetobacter baumannii LUH5534 Containing a d-Galactose 4,6-Pyruvic Acid Acetal.
Type K82 capsular polysaccharide (CPS) was isolated from Acinetobacter baumannii LUH5534. The structure of a linear tetrasaccharide repeating unit of the CPS was established by sugar analysis along with one- and two-dimensional 1H and 13C NMR spectroscopy. Proteins encoded by the KL82 capsule gene cluster in the genome of LUH5534 were assigned to roles in the synthesis of the K82 CPS. In particular, functions were assigned to two new glycosyltransferases (Gtr152 and Gtr153) and a novel pyruvyltransferase, Ptr5, responsible for the synthesis of d-galactose 4,6-(R)-pyruvic acid acetal.


Effect of intratracheal gallium arsenide administration on delta-aminolevulinic acid dehydratase in rats: relationship to urinary excretion of aminolevulinic acid.
Exposure to gallium arsenide (GaAs) is a potential hazard in the semiconductor industry and there is a need for specific biological indicators of exposure/toxicity for this compound. These studies examined effects of GaAs exposure on the heme biosynthetic pathway enzyme delta-aminolevulinic acid dehydratase (ALAD). Male CD rats received GaAs suspensions at doses of 50, 100, or 200 mg/kg via a single intratracheal instillation. Six days after treatment a dose-dependent inhibition of blood ALAD was observed with activity decreasing to 5% of controls at the highest dose, with a concomitant marked increase in the urinary excretion of aminolevulinic acid (ALA). Inhibition of blood ALAD following administration of GaAs was maximal (30% of control) 3 to 6 days postexposure and returned to approximately control values on day 18. Urinary excretion of ALA was maximal 3 to 6 days postexposure and recovered toward control values at 18 days. Inhibition of kidney and liver ALAD following GaAs exposure was also evident. Intratracheal instillation of silica did not alter the activity of ALAD in blood, liver, or kidney. Marked increases in lung wet weight/body weight ratios were evident in lungs of silica- and GaAs-treated rats. Histopathological changes in the lungs were characterized by multifocal granulomas following silica treatment and Type II pneumocyte hyperplasia following GaAs treatment; mild necrosis was evident in both groups. Rats treated with 100 mg/kg GaAs exhibited swelling of kidney proximal tubule mitochondria 6 days following exposure. Silica and GaAs exposure produced marked decreases in cumulative weight gain. The concentration of gallium required to achieve half-maximal inhibition of ALAD in vitro was 200-fold less in blood and 40-fold less in kidney and liver than that required for arsenite and the inhibition was partially prevented by excess zinc. These data suggest that gallium is the primary inhibitor of ALAD following dissolution of GaAs in vivo and that competition for or displacement of zinc from the enzyme active site may be involved in the mechanism of inhibition. The data also demonstrated the utility of including a particulate control group when assessing the chemical-induced toxicity of compounds administered intratracheally as particulate suspensions. Finally, measurement of heme precursors, e.g., ALA, in urine coupled with assay of red blood cell ALAD activity may be of value as an early biological indicator of GaAs exposure and/or toxicity.


Improving the photovoltaic performance of perovskite solar cells with acetate.
In an all-solid-state perovskite solar cell, methylammonium lead halide film is in charge of generating photo-excited electrons, thus its quality can directly influence the final photovoltaic performance of the solar cell. This paper accentuates a very simple chemical approach to improving the quality of a perovskite film with a suitable amount of acetic acid. With introduction of acetate ions, a homogeneous, continual and hole-free perovskite film comprised of high-crystallinity grains is obtained. UV-visible spectra, steady-state and time-resolved photoluminescence (PL) spectra reveal that the obtained perovskite film under the optimized conditions shows a higher light absorption, more efficient electron transport, and faster electron extraction to the adjoining electron transport layer. The features result in the optimized perovskite film can provide an improved short-circuit current. The corresponding solar cells with a planar configuration achieves an improved power conversion efficiency of 13.80%, and the highest power conversion efficiency in the photovoltaic measurements is up to 14.71%. The results not only provide a simple approach to optimizing perovskite films but also present a novel angle of view on fabricating high-performance perovskite solar cells.


The central origin of efferent pathways in the carotid sinus nerve of the cat.
The application of horseradish peroxidase to the central cut end of the carotid sinus nerve of the cat produced retrograde labeling of neurons in the ipsilateral medulla in the region of the nucleus ambiguus at anterior-posterior coordinates -8 to -10.5. These data coupled with previous electrophysiological observations suggest that the nucleus ambiguus may be the origin of an efferent inhibitory pathway to the carotid body.


Cytophotometric analyses of brain neuronal RNA in soman intoxicated rabbits.
Quantitative azure B-RNA cytophotometry was used to monitor metabolic responses of individual neurons of the motor cortex (layer V) and caudate nucleus of soman (pinacolyl methylphosphonofluoridate) poisoned rabbits. Time- and dose-dependent RNA responses were related to the extent of acetylcholinesterase (AChE) inactivation of these 2 brain regions and to overt behavioral manifestations of toxication. A complex pattern of RNA responses was evidenced, with RNA depletion occurring at both arousal and convulsive doses of soman. In general, RNA changes paralleled previously reported metabolic responses observed in soman toxicated rats and mice: (1) linear dose-dependent suppression of RNA was evidenced during the depressant phase but not in the acute excitatory phase of toxication; and (2) RNA depletion was more severe following than during the appearance of excitatory symptoms. These data indicate that soman poisoning results in metabolic correlates of impaired rather than excessive CNS activation. It is postulated that metabolic disturbances are related to blockade of central cholinergic excitation, and that disruption of functionally integrated synaptic activity forms a critically important aspect of toxication.


Large coronary arteries in humans are responsive to changing blood flow: an endothelium-dependent mechanism that fails in patients with atherosclerosis.
Changes in blood flow can alter vasomotion of conduit arteries. This study examined vasomotor responses to incremental blood flow induced by papaverine in the epicardial arteries of 10 patients with angiographically normal coronary arteries (group 1) and in 14 patients with arterial irregularities (group 2) using quantitative angiography and Doppler ultrasound flow velocity measurements. An increase in coronary blood flow of 384.3 +/- 32.8% (p less than 0.001) in group 1 patients was associated with dilation of the proximal coronary artery segment and a 23.2 +/- 4.6% increase in cross-sectional area (p less than 0.001). In contrast, in group 2 patients a similar increase in coronary blood flow of 339.3 +/- 18.7% (p less than 0.001) was associated with mixed responses and a modest net constriction in cross-sectional area of -7.4 +/- 2.8% (p less than 0.05). The dilation response to nitroglycerin was intact in group 1 (31.7 +/- 4.2%, p less than 0.001) and in group 2 (26.4 +/- 3.2%, p less than 0.001). In five patients from group 1 acetylcholine, an endothelium-dependent dilator, produced an increase in cross-sectional area of 20.7 +/- 4.6% (p less than 0.05) that paralleled the response to an increase in flow in the same segment (a 24.3 +/- 6.1% increase in cross-sectional area, p less than 0.05). Five group 2 patients demonstrated a vasoconstrictor response to acetylcholine (a -22.8 +/- 3.4% decrease in cross-sectional area, p less than 0.05) together with an impaired dilation response to incremental flow (a -6.4 +/- 3.2% decrease in cross-sectional area).(ABSTRACT TRUNCATED AT 250 WORDS)


Poorly differentiated adenocarcinoma with signet ring cells of the gallbladder producing a high level of alpha-fetoprotein: A case report.
Alpha-fetoprotein (AFP) can become elevated in hepatocellular carcinoma (HCC), yolk sac tumors and other malignant tumors of various organs. Herein, we present a case of AFP-producing gallbladder carcinoma with signet ring cells successfully treated with laparoscopic whole-layer cholecystectomy. A 69-year-old woman was found to have increased levels of the tumor marker AFP (16.1 to 1474 ng/mL), and an irregularly shaped mass 22 mm in size in the gallbladder at 5 months follow-up after transcatheter arterial chemoembolization and radiofrequency ablation for HCC in segment 3 of the liver. As no additional metastases were detected, we diagnosed the patient with either AFP-producing gallbladder carcinoma (cT2aN0M0, cStage IIa, UICC 8th) or gallbladder metastasis from HCC. Laparoscopic whole-layer cholecystectomy was performed, and histological examination revealed AFP positive poorly differentiated adenocarcinoma with signet ring cells (pT2bN0cM0, pStage IIb, UICC 8th). AFP levels were remarkably decreased after operation (15 ng/mL), and no residual tumors or distant metastases were observed on contrast enhanced computed tomography (CE-CT), indicating that the tumor was an AFP-producing gallbladder carcinoma rather than metastasis of HCC. Due to the similar developmental origin of the liver and gallbladder, gallbladder carcinoma could produce AFP in some cases. Considering that AFP is predominantly synthesized during embryogenesis, the status of cellular differentiation would be associated with the ability to synthesize AFP. When no lesions except for in the gallbladder can account for elevated AFP levels, clinicians should consider AFP-producing gallbladder carcinoma.


A comparison of granisetron as a single agent with conventional combination antiemetic therapies in the treatment of cytostatic-induced emesis. The Granisetron Study Group.
The safety and efficacy of intravenous granisetron were compared with combinations of conventional antiemetics in two single-blind, parallel-group studies which have been reported previously. In this review updated data from both studies is presented. In both studies granisetron (40 micrograms/kg) was given as a single 5-min infusion before chemotherapy with two additional doses allowed to control subsequent nausea and vomiting. All patients were naive to chemotherapy. Patients due to receive cisplatin (greater than 49 mg/m2) were randomly assigned to receive either granisetron alone or metoclopramide (3 mg/kg) plus dexamethasone (12 mg) given prophylactically followed by an 8-h infusion of metoclopramide (4 mg/kg). In the 24 h after the start of chemotherapy 70% of granisetron-treated patients and 67% of comparator group were complete responders. In patients due to receive moderately emetogenic chemotherapy, granisetron was compared with chlorpromazine (up to 200 mg/24 h) plus dexamethasone (12 mg). Twenty-four hour efficacy was significantly higher in the granisetron group with complete response in 68% of patients compared to 47% in the comparator group (P less than 0.001). A subset of 40 patients in this study were crossed over to receive the alternative antiemetic on their next cycle of chemotherapy. A significant majority of patients (32/34; 94%) preferred granisetron (P less than 0.001). Around 80% of the granisetron-treated patients in both groups required only a single prophylactic dose of granisetron. Following the first additional dose of granisetron, around 87% of patients reported symptoms to be improved or resolved. Adverse experience reporting was higher in the comparator groups with somnolence and extrapyramidal reactions representing the most common events. Headache was the most commonly reported adverse experience in granisetron-treated patients. Granisetron has proved safe and effective in controlling chemotherapy-induced emesis and is more convenient to administer than conventional antiemetics.


An inventory of crosstalk between ubiquitination and other post-translational modifications in orchestrating cellular processes.
Ubiquitination is an important post-translational modification (PTM) that regulates a large spectrum of cellular processes in eukaryotes. Abnormalities in ubiquitin signaling underlie numerous human pathologies including cancer and neurodegeneration. Much progress has been made during the last three decades in understanding how ubiquitin ligases recognize their substrates and how ubiquitination is orchestrated. Several mechanisms of regulation have evolved to prevent promiscuity including the assembly of ubiquitin ligases in multi-protein complexes with dedicated subunits and specific post-translational modifications of these enzymes and their co-factors. Here, we outline another layer of complexity involving the coordinated access of E3 ligases to substrates. We provide an extensive inventory of ubiquitination crosstalk with multiple PTMs including SUMOylation, phosphorylation, methylation, acetylation, hydroxylation, prolyl isomerization, PARylation, and O-GlcNAcylation. We discuss molecular mechanisms by which PTMs orchestrate ubiquitination, thus increasing its specificity as well as its crosstalk with other signaling pathways to ensure cell homeostasis.


A survey of aflatoxin B1 and total aflatoxin contamination in baby food, peanut and corn products sold at retail in Indonesia analysed by ELISA and HPLC.
Aflatoxin contamination has been well known as a world-wide health-threatening problem in tropical countries including Indonesia. This research was undertaken to determine the degree of aflatoxin contamination in different Indonesian foodstuffs. A preliminary survey was carried out to evaluate the level of total aflatoxin (AfT) and aflatoxin B1 (AfB1) contamination of baby foods, peanut products, and corn products, which were purchased from traditional markets and supermarkets in Indonesia during the year 2001-2002. Eighty two peanut products, 12 baby foods products, and 11 corn products from different brands were analysed for AfT and AfB1 using the Enzyme-Linked Immunosorbent Assay (ELISA) method. The results indicate that, of the brands analysed, 35% of the peanut products were contaminated with aflatoxins at various levels (range 5 to 870 μg/kg). Peanut-chilli sauces had the highest percentage of AfT contamination 9/12 (75%), which was followed by traditional snacks 5/11 (45%), peanut butter 4/11 (40%), flour egg coated peanut 6/16 (37%), and peanut cake 3/10 (30%). Fried peanuts and roasted peanut were found to contain aflatoxin at relatively lower percentages of 9% and 8%, respectively. From the 12 analysed baby food samples, on the other hand, no sample was found to be contaminated with aflatoxins. Two of 11 samples (18%) of corn based products were contaminated with AfT, ranging between 5.8 and 12.4 μg/kg. Additionally, 30 selected samples in different concentration ranges were further analysed to verify the correlation between ELISA and HPLC techniques and results were compared.


[The early enteral feeding in patients after the surgical treatment of duodenal ulcer].
The author has analyzed the data of 163 patients operated because of their duodenal ulcer disease. There were in existence 30% of the first degree, 53% of the second degree and 17% of third degree emaciated patients. The author developed a new scheme of the enteral feeding. This new scheme proved to be effective based on the analysis of biochemical indices in patients at the early postopeartive period.


Piperine suppresses tumor growth and metastasis in vitro and in vivo in a 4T1 murine breast cancer model.
To investigate the effects of piperine, a major pungent alkaloid present in Piper nigrum and Piper longum, on the tumor growth and metastasis of mouse 4T1 mammary carcinoma in vitro and in vivo, and elucidate the underlying mechanisms. Growth of 4T1 cells was assessed using MTT assay. Apoptosis and cell cycle of 4T1 cells were evaluated with flow cytometry, and the related proteins were examined using Western blotting. Real-time quantitative PCR was applied to detect the expression of matrix metalloproteinases (MMPs). A highly malignant, spontaneously metastasizing 4T1 mouse mammary carcinoma model was used to evaluate the in vivo antitumor activity. Piperine was injected into tumors every 3 d for 3 times. Piperine (35-280 μmol/L) inhibited the growth of 4T1 cells in time- and dose-dependent manners (the IC(50) values were 105 ± 1.08 and 78.52 ± 1.06 μmol/L, respectively, at 48 and 72 h). Treatment of 4T1 cells with piperine (70-280 μmol/L) dose-dependently induced apoptosis of 4T1 cells, accompanying activation of caspase 3. The cells treated with piperine (140 and 280 μmol/L) significantly increased the percentage of cells in G(2)/M phase with a reduction in the expression of cyclin B1. Piperine (140 and 280 μmol/L) significantly decreased the expression of MMP-9 and MMP-13, and inhibited 4T1 cell migration in vitro. Injection of piperine (2.5 and 5 mg/kg) dose-dependently suppressed the primary 4T1 tumor growth and injection of piperine (5 mg/kg) significantly inhibited the lung metastasis. These results demonstrated that piperine is an effective antitumor compound in vitro and in vivo, and has the potential to be developed as a new anticancer drug.


A case of epidemic keratoconjunctivitis complicated by Alcaligenes xylosoxidans infection.
To report a case of epidemic keratoconjunctivitis complicated by Alcaligenes xylosoxidans. A 37-year-old man suffered epidemic keratoconjunctivitis in both eyes. Eleven days later, he developed a corneal ulcer in his left eye. Bacterial staining, culture, and antibiotics sensitivity test were performed from a corneal scrape. The cultures revealed a growth of Alcaligenes xylosoxidans, and the patient was treated with ceftazidime and levofloxacin, based on the sensitivity test results. After 21 days of treatment, the infection was resolved with mild scaring and final vision in the left eye of 20/20. Alcaligenes xylosoxidans should be considered a rare but potential pathogen able to produce comeal ulcer complication in epidemic keratoconjunctivitis.


2-Chloro-5-fluoro-6-methyl-N-o-tolyl-pyrimidin-4-amine.
In the title compound, C12H11ClFN3, the benzene ring forms a dihedral angle of 72.43 (5)° with the pyrimidine ring. In the crystal, N-H⋯N hydrogen bonds link the mol-ecules into a chain running along the c axis.


A novel multi-components hierarchical porous composite prepared from solid wastes for benzohydroxamic acid degradation.
In this study, a novel carbon-wrapped-iron hierarchical porous catalyst (Fe/C-Mn800) was prepared from electrolytic manganese residue (EMR) and sewage sludge (SS), which showed outstanding degradation ability toward benzohydroxamic acid (BHA, nearly 90 % was removed within 60 min) with low metal leaching rate. Mechanism exploration found transition metal ions (Fe and Mn) can serve as electron acceptors and facilitate the generation of persistent free radicals (PFRs). These transition metal ions and PFRs mainly participated in the single-electron pathway via activating PMS to generate a large amount of reactive oxygen species (ROS). While the electron negative graphitic N and CO groups not only improve the electronegatively of catalyst, but also acted as the electron sacrificers to favor the electron transfer and directly oxidized the absorbed BHA through the ternary activated outer-sphere complexes. Eley-Rideal (E-R) and Langmuir-Hinshelwood (L-H) analysis further demonstrated the crucial role of pre-adsorption during the degradation process. This work provided a deep insight into the degradation mechanism of metal/carbon composite and promising opportunity widened the horizon of the high-value utilization of EMR and SS.


Long-term memory formation in chicks is blocked by 2-deoxygalactose, a fucose analog.
When day-old chicks are trained on a passive avoidance task there is enhanced synthesis of glycoproteins. Bilateral intracerebral injections of 20 mumole of 2-deoxygalactose (2-D-gal), administered just before and just after training on the task, produce amnesia for the avoidance. Amnesia develops slowly over the first hour and persists for at least 24 h subsequently. If 2-D-gal injections are administered 4 h prior to the training or delayed for 3 h after training, no amnesia occurs. Apart from a brief initial suppression of pecking following injection there are no effects of 2-D-gal on other observed behaviors of the birds. Within the first hour this dose of 2-D-gal inhibits [3H]fucose incorporation into acid-insoluble material by 26% (or 68%, calculated relative to free pool fucose). The amnestic effect of 2-D-gal is not shown by galactose, glucose, fucose, or 2-D-glucose. Injecting 40 mumole of galactose simultaneously with the 2-D-gal abolishes the 2-D-gal-induced amnesia; 40 mumole of fucose, however, does not abolish the amnesia. The utility of 2-D-gal as an agent for analyzing the role of glycoproteins in memory formation is discussed.


Managing the cystic osteochondral defect: allograft or autograft.
Osteochondral lesions of the talus are generally benign, and many heal or are not symptomatic. A subset of these defects progress to large cystic lesions, which have a less favorable prognosis. The treatment options are joint preservation or sacrifice. Joint salvage entails marrow stimulation techniques or hyaline cartilage replacement with allograft or autograft. When lesions reach greater than 3 cm(2) or Raikin class IV or become uncontained on the shoulders of the talus, autografting techniques become more challenging. Osteochondral allografting may be a better surgical option, often achievable without a malleolar osteotomy for exposure.


Evaluation of seroepidemiological associations between HIV-infection, hepatitis B and other sexually transmitted diseases in African patients.
To assess the possible role of sexually transmitted diseases as cofactors for the spread of AIDS, 248 adult patients were tested for the presence of antibodies against human immunodeficiency virus (HIV), hepatitis B virus (HBV) and syphilis. The survey was conducted in a hospital at Kagondo, Kagera Region, Northwest Tanzania, Africa. Subjects were randomly chosen from the outpatient clinic to include those with and without sexually transmitted diseases, as well as AIDS/pre-AIDS patients. The data were univariately and multivariately analysed by linear logit models, including interactions of demographic parameters. The results obtained reveal a strong association between the presence of antibodies against HIV, syphilis and HBV, respectively. The HBV/HIV-correlation remained stable in the multivariate analysis including interactions of social parameters, in contrast to the syphilis/HIV-correlation. We assume that this reflects the lower virulence of HBV as compared to that of syphilis. The prevalence of anti-HBV antibodies seems to be a more reliable marker for high sexual activity than those against syphilis. The possibility that HBV and HIV act as cofactors for each other's transmission could not be ruled out.


Fluorescent immunochromatographic test strip for therapeutic drug monitoring of methotrexate with high sensitivity and wide dynamic range.
As a front-line chemotherapeutic drug for maintenance and consolidation therapy, methotrexate (MTX) has widely been applied to treat various tumors and some inflammatory diseases. However, because of its severe toxicity ascribed to low selectivity, it is necessary to monitor therapeutic drugs in high-dose MTX therapeutic regimens to ensure treatment safety. In this work, we developed a fluorescent immunochromatographic test strip (FITS) for monitoring MTX by employing time-resolved fluorescent microspheres as signal probes. With a competitive immunoassay mode, the FITS for MTX shows a super-wide dynamic range of 10 pM-10 μM, covering the entire clinical therapeutic concentration range of MTX. Therapeutic drug monitoring of MTX can be achieved within 7 min with high specificity, facilitating the timely rescue of drug poisoning led by high-dose MTX treatment. The method was employed for monitoring MTX in the spiked human serum, urine, and milk, showing acceptable recoveries ranging from 94.0 to 110.0%. The established FITS has been applied to MTX detection in serum obtained from high-dose MTX treatment. The results from FITS and enzyme multiplied immunoassay technique showed no significant difference, suggesting its reliability for usage in real biological samples. The device shows promise in point-of-care therapeutic drug monitoring for resource-limited countries and institutes, which significantly facilitates overcoming the lag time between sampling and results.


Effectiveness and tolerability of adjunctive perampanel in the treatment of pediatric patients with uncontrolled epilepsy: A retrospective, single-center, real-world study.
The main aim of this study was to assess the efficacy, safety, and tolerability of adjunctive perampanel (PER) in the treatment of children and adolescents with epilepsy. Pediatric patients who visited the pediatric epilepsy clinic of Henan Provincial People's Hospital between May 2020 and December 2021 were recruited. All participants were treated with PER as adjunctive therapy and were seen routinely (minimum: a baseline and 12-week visit). The efficacy and tolerability of adjunctive PER for the treatment of epilepsy were investigated. One hundred and fourteen patients were enrolled, among whom 7 (6.1%) were lost to follow-up. At 12 weeks, the responder rate and the seizure-free rate were 56.1% (60/107) and 32.7% (35/107), respectively. The responder rate increased with the duration of PER administration and was significantly higher when PER was used as an early add-on (after ≤2 prior antiseizure medications (ASMs)) than a late add-on (after >2 prior ASMs). However, there was no significant difference in the treatment efficacy of adjunctive PER in patients with different epilepsy etiologies or types. Adverse events, including irritability, dizziness, somnolence, ataxic gait, weight gain, and tinnitus, were reported in thirty-two patients (29.9%). In a routine clinical setting of pediatric patients with epilepsy, good effectiveness and tolerability of adjunctive PER were demonstrated. Notably, patients initiating PER as an early add-on showed a better seizure outcome than those initiating PER as a late add-on.


Enhanced Osteogenesis of Adipose-Derived Stem Cells by Regulating Bone Morphogenetic Protein Signaling Antagonists and Agonists.
Although adipose-derived stem cells (ASCs) are an attractive cell source for bone tissue engineering, direct use of ASCs alone has had limited success in the treatment of large bone defects. Although bone morphogenetic proteins (BMPs) are believed to be the most potent osteoinductive factors to promote osteogenic differentiation of ASCs, their clinical applications require supraphysiological dosage, leading to high medical burden and adverse side effects. In the present study, we demonstrated an alternative approach that can effectively complement the BMP activity to maximize the osteogenesis of ASCs without exogenous application of BMPs by regulating levels of antagonists and agonists to BMP signaling. Treatment of ASCs with the amiloride derivative phenamil, a positive regulator of BMP signaling, combined with gene manipulation to suppress the BMP antagonist noggin, significantly enhanced osteogenic differentiation of ASCs through increased BMP-Smad signaling in vitro. Furthermore, the combination approach of noggin suppression and phenamil stimulation enhanced the BMP signaling and bone repair in a mouse calvarial defect model by adding noggin knockdown ASCs to apatite-coated poly(lactic-coglycolic acid) scaffolds loaded with phenamil. These results suggest novel complementary osteoinductive strategies that could maximize activity of the BMP pathway in ASC bone repair while reducing potential adverse effects of current BMP-based therapeutics. Although stem cell-based tissue engineering strategy offers a promising alternative to repair damaged bone, direct use of stem cells alone is not adequate for challenging healing environments such as in large bone defects. This study demonstrates a novel strategy to maximize bone formation pathways in osteogenic differentiation of mesenchymal stem cells and functional bone formation by combining gene manipulation with a small molecule activator toward osteogenesis. The findings indicate promising stem cell-based therapy for treating bone defects that can effectively complement or replace current osteoinductive therapeutics.


Neural substrates associated with evaluative processing during co-activation of positivity and negativity: a PET investigation.
Affective symmetries, such as the positivity offset and negativity bias, have been postulated to be attributable to distinct activation functions of the positive and negative affect systems. We investigated the neural substrates that are engaged when the positive and negative affect systems undergo parallel and integrative processing. Eleven subjects were scanned using H(2)(15)O PET during choosing the subjective feeling produced by a stimulation pair of pictures or words. Four different conditions were designed for contrast: pure positivity, pure negativity, positivity offset, and negativity bias. The dorsolateral prefrontal activation was associated with positivity offset and negativity bias condition, whereas the ventromedial prefrontal activation, together with limbic and subcortical activations, was associated with pure positivity and pure negativity condition. The results indicated that positivity offset and negativity bias are not merely due to asymmetric activations of the positive and negative systems, but integrative processing of higher neocortical levels is involved.


Geospatial modelling of electromagnetic fields from mobile phone base stations.
There is concern that exposure to radio frequency electromagnetic fields (RF-EMF) from mobile phone base stations might lead to adverse health effects. In order to assess potential health risks, reliable exposure assessment is necessary. Geospatial exposure modelling is a promising approach to quantify ambient exposure to RF-EMF for epidemiological studies involving large populations. We modelled RF-EMF for Amsterdam, The Netherlands by using a 3D RF-EMF model (NISMap). We subsequently compared modelled results to RF-EMF measurements in five areas with differing built-up characteristics (e.g., low-rise residential, high-rise commercial). We performed, in each area, repeated continuous measurements along a predefined ~2 km long path. This mobile monitoring approach captures the high spatial variability in electric field strengths. The modelled values were in good agreement with the measurements. We found a Spearman correlation of 0.86 for GSM900 and 0.85 for UMTS between modelled and measured values. The average measured GSM900 field strength was 0.21 V/m, and UMTS 0.09 V/m. The model underestimated the GSM900 field strengths by 0.07 V/m, and slightly overestimated the UMTS field strengths by 0.01 V/m. NISMap provides a reliable way of assessing environmental RF-EMF exposure for epidemiological studies of RF-EMF and health in urban areas.


Ciliated hepatic foregut cyst: a rare cystic liver lesion.
Ciliated hepatic foregut cysts are an unusual congenital cause of cystic liver lesions. Although most are benign, 4.4% of reported cases have been shown to harbor squamous cell carcinoma. Diagnostic uncertainty or misdiagnosis frequently results in surgical exploration. We present a case of a ciliated hepatic foregut cyst and review this uncommon condition.


Psychometric Properties of the Czech Version of the Falls Efficacy Scale-International in Patients with Early-Stage Dementia.
A fear of falling marks an important psychological factor connected with a reduction in the life space of people with dementia. The Czech version of the Falls Efficacy Scale-International (FES-I) has not been validated in patients with early-stage dementia. The tests were administered to 282 patients with early-stage dementia. The test battery included the following: the FES-I, the Short Physical Performance Battery, the Geriatric Depression Scale, the Bristol Activity Daily Living Scale, and the Quality of Life-Alzheimer's Disease Scale. Internal reliability (Cronbach's α and intraclass correlation [ICC]), Pearson's and Spearman's correlations, exploratory factor analysis, and a t test for independent samples were used for statistical analyses. The Czech version of the FES-I had excellent internal and test-retest reliability (Cronbach's α = 0.98, ICC = 0.90; 95' CI 0.82-0.94). Factor analysis suggested 2 relevant factors. A significantly higher FES-I score was associated with patients with early-stage dementia who were older (p = 0.003) or female (p = 0.001), lived alone (p = 0.0001), spent >8 h a day alone (p = 0.032), used mobility aids (p < 0.0001), or had severe hearing (p = 0.004) or vision impairment (p < 0.0001) or a lower education (r = -0.16, p = 0.007). The Czech version of the FES-I had very good reliability and validity and may be useful in future cross-cultural comparisons in research among patients with early-stage dementia.


Current approaches to management of depression in Parkinson's Disease.
Depression is a common problem in patients affected by Parkinson's Disease (PD). In many cases, treatment with antidepressants is necessary, and the choice of the most suitable drug is often controversial, as many factors need to be considered that may complicate the development of the disease, including potential side effects of antidepressant therapy. Selective Serotonin Reuptake Inhibitors (SSRIs) and Tricyclic Antidepressants (TCAs) are the two major categories of antidepressants used. Tricyclics have been shown to be effective in most cases, but some side effects (orthostatic hypotension, sedation, cognitive and anticholinergic effects) may present problems. In contrast, SSRI appear to be better tolerated, but some reports indicate a potential worsening of the parkinsonism. Other recently introduced medications need further investigation. The main therapeutic strategies, as reported in the international literature according to efficacy and tolerability, interactions with antiparkinsonian or concomitant drugs and possible effects on worsening of PD, are presented.


Childhood family structure and personality disorders in adulthood.
The association between childhood family structure and sociodemographic characteristics and personality disorders (PDs) in a general population sample was studied. This study is a substudy of the prospective Northern Finland 1966 Birth Cohort Project with 1588 young adult subjects. The case-finding methods according to the DSM-III-R criteria for PDs were: (1) Structured Clinical Interview for DSM-III-R (SCID) for 321 cases who participated in a 2-phase field study, (2) Finnish Hospital Discharge Register data, and (3) analysis of the patient records in public outpatient care in 1982-1997. Statistical analyses were performed on the association between PDs and family background factors. Altogether 110 (7.0%) of the subjects had at least one probable or definite PD. After adjusting for confounders (gender, parental social class and parental psychiatric disorder) the results indicated that single-parent family type in childhood was associated with cluster B PDs in adulthood. Being an only child in childhood was associated with cluster A PDs. No special childhood risk factors were found for cluster C PDs. Results suggest that single-parent family type at birth and being an only child in the 1960s are associated with PD in adulthood. Further studies are needed to explore the psychosocial aspects of family environment which may nowadays promote vulnerability to PDs in adulthood.


Design and synthesis of novel Flavone-based histone deacetylase inhibitors antagonizing activation of STAT3 in breast cancer.
Histone deacetylases (HDACs) inhibitors have demonstrated a great clinical achievement in hematological malignancies. However, the efficacy of HDACs inhibitors in treating solid tumors remains limited due to the complicated tumor microenvironment. In this study, we designed and synthesized a class of novel HDACs inhibitors based on the structure of flavones and isoflavones, followed by biological evaluation. To be specific, a lead compound 15a was discovered with strong anti-proliferative effects on a variety of solid tumor cells, especially for breast cancer cells with resistance to SAHA. Studies demonstrated that 15a could significantly inhibit the activity of HDAC 1, 2, 3 (class I) and 6 (class IIB), leading to a dose-dependent accumulation of acetylated histones and α-Tubulin, cell cycle arrest (G1/S phase) and apoptosis in breast cancer cells. Furthermore, the lead compound 15a could also antagonize the activation of STAT3 induced by HDACs inhibition in some breast cancer cells, which further reduced the level of pro-survive proteins in tumor cells and enhanced anti-tumor activity regulated by STAT3 signaling in vivo. Overall, our findings demonstrated that the novel compound 15a might be a HDACs inhibitor candidate, which could be used as promising chemotherapeutic agent for breast cancer.


Job loss from poor health, smoking and obesity: a national prospective survey in France.
Health selection into unemployment may be either direct or operate by reference to health-related behaviours rather than health per se (indirect selection). Panel data are desirable to investigate selection effects, and the two types of selection processes may be concurrent. We examine jointly the roles of health and health-related behaviours as precursors of unemployment, in order to disentangle direct from indirect selection processes. The data of a multi-round nationally representative health survey in France were analysed longitudinally, based on three data collection rounds: 1992-5, 1996-8 and 2000-2. Following employees salaried in the private sector and aged 30-54 years at baseline, we explored through logistic regression the influence of non-optimal self-rated health, smoking and obesity on the risk of being found unemployed 4 years later. After adjustment for self-rated health, obesity was found to be a significant precursor of unemployment in women, and heavy smoking had that role in men. After adjustment for smoking and obesity, poor health at baseline was found to be a significant precursor of unemployment in both genders. Those findings confirm the intrinsic role of poor health and of health-related behaviours as precursors of unemployment, with gender-specific patterns for the latter. Public policy prescriptions regarding employees' protection from job insecurities should integrate appropriate accommodations of health limitations, and the personal factors underlying unfavourable work and health behaviours should be investigated, in order to thwart indirect selection phenomena.


Variation in carbon isotope ratios of Sempervivoideae species from different habitats of Teneriffe in the spring.
According to carbon isotope ratios, species of the Sempervivoideae from Teneriffe show in general a tendency for increased participation of dark CO2 fixation via PEP-carboxylase in total carbon fixation as habitats become drier and warmer. Certain species are found in cool moist habitats and exhibit C3-like δ13C values. Other species occur in warm dry habitats and exhibit δ13C values which indicate strong Crassulacean Acid Metabolism. A third group of species shows intermediate δ13C values which are more C3-like in cool moist habitats and which indicate increased dark fixation in warmer and drier situations. Included in this group is Aeonium holochrysum, which of the Sempervivoideae of Teneriffe is thought to be most closely related to the common ancestor (Lems 1960). Comparison of CO2 gas exchange of several species under identical environmental conditions reveals differences among species in the ability to regulate CO2 fixation in the light and in the dark which may have arisen in the process of adaptive radiation.


Free and protein-conjugated polyamines in mouse epidermal cells. Effect of high calcium and retinoic acid.
We have investigated polyamine metabolism in primary cultures of mouse epidermal cells. These cells, which grow at low Ca2+ levels as a monolayer with characteristics of basal cells, terminally differentiate when the extracellular Ca2+ level is raised above 1 mM. The cellular levels of free polyamines were measured, and, after incubation of cell cultures with [3H]putrescine, the distribution of label in both acid-soluble and acid-insoluble cellular components was examined. Free polyamine levels were reduced in cells induced to differentiate. Treatment with retinoic acid, which prevents differentiation and causes increased proliferation, resulted in an increase in free putrescine. Upon adjustment of the calcium concentration to a level that induces differentiation, the enzyme transglutaminase was activated, and a concomitant increase in the level of both protein-bound mono- and bis-gamma-glutamyl derivatives of putrescine and spermidine was observed. Isolation of a material of apparent molecular weight about 6000 which contains only mono-gamma-glutamylpolyamines and the finding of both mono- and bis-gamma-glutamylpolyamines in the protein fraction containing cornified cell envelopes provided the basis for speculation on polyamines in envelope formation. Our data suggest that polyamines play a role during epidermal cell differentiation through transglutaminase-mediated post-translational modification.


The mixed subtype has a worse prognosis than other histological subtypes: a retrospective analysis of 217 patients with metaplastic breast cancer.
Metaplastic breast cancer (MpBC) is an aggressive subtype of all breast cancer. We aimed to investigate the clinicopathological features, treatments and prognoses of MpBC patients. We collected the data from MpBC patients diagnosed at Tianjin Medical University Cancer Hospital from 2010 to 2017. Kaplan Meier curves and Cox regression model were used to evaluating clinical outcomes and prognostic factors. After removing baseline differences by propensity score matching (PSM), we analyzed the prognosis between MpBC patients and invasive ductal carcinomas of no special type (IDC-NST) patients. A total of 217 MpBC patients were subsumed. Of all histological subtypes, 45.1% were mixed subtypes, followed by with mesenchymal differentiation (27.2%), pure squamous (15.2%) and pure spindle (12.4%) subtypes. 69.6% of MpBC were triple-negative, 25.3% and 6.5% were HR-positive and HER2-positive. MpBC patients had worse survival compared to IDC-NST patients, with 5-year RFS of 73.8 and 83.6% (HR = 1.177 95%CI (1.171-2.676) P = 0.0068), and 5-year BCSS of 79.0% and 89.7% (HR = 2.187 95%CI (1.357-3.523) P = 0.0013). In the multivariate COX model, AJCC stage, mixed subtype and chemotherapy were independent prognostic factors. Mixed MpBC is more aggressive than pure and with heterologous mesenchymal differentiation subtypes. And whether squamous or spindle MpBC, mixed forms have shorter outcomes than pure forms. MpBCs are associated with poorer prognoses than IDC-NSTs. They are heterogeneous with different clinicopathological features and clinical outcomes between histological subtypes. Pure and with heterologous mesenchymal differentiation subtypes have more survival benefits than the mixed subtype.


Prediction of cesarean delivery in class III obese nulliparous women: An externally validated model using machine learning.
class III obese women, are at a higher risk of cesarean section during labor, and cesarean section is responsible for increased maternal and neonatal morbidity in this population. the objective of this project was to develop a method with which to quantify cesarean section risk before labor. this is a multicentric retrospective cohort study conducted on 410 nulliparous class III obese pregnant women who attempted vaginal delivery in two French university hospitals. We developed two predictive algorithms (a logistic regression and a random forest models) and assessed performance levels and compared them. the logistic regression model found that only initial weight and labor induction were significant in the prediction of unplanned cesarean section. The probability forest was able to predict cesarean section probability using only two pre-labor characteristics: initial weight and labor induction. Its performances were higher and were calculated for a cut-point of 49.5% risk and the results were (with 95% confidence intervals): area under the curve 0.70 (0.62,0.78), accuracy 0.66 (0.58, 0.73), specificity 0.87 (0.77, 0.93), and sensitivity 0.44 (0.32, 0.55). this is an innovative and effective approach to predicting unplanned CS risk in this population and could play a role in the choice of a trial of labor versus planned cesarean section. Further studies are needed, especially a prospective clinical trial. French state funds "Plan Investissements d'Avenir" and Agence Nationale de la Recherche.


Bladder management and quality of life after spinal cord injury.
This study examines the quality of life among individuals with spinal cord injury requiring assistance for bowel and bladder management vs. those with independent control of bowel and bladder. Two groups of 53 individuals each were matched case for case on age, education, sex, race, and lesion level. Outcome measures included the Satisfaction With Life Scale, the Craig Handicap Assessment and Reporting Technique (CHART), and the SF-12. Satisfaction with life was significantly lower among dependent individuals with impaired bowel and bladder functioning as compared with individuals with independent bowel and bladder control. Similarly, dependent individuals reported greater self-reported handicap (CHART) than independent individuals in the areas of physical independence, mobility, and occupational functioning. However, dependent and independent individuals did not differ in the areas of social integration and economic self-sufficiency. Item analysis on the CHART item assessing number of social contacts initiated in the previous month suggested that dependent individuals may have difficulty initiating new social contacts. Independent individuals reported better overall physical health (SF-12) than dependent individuals. Mental health (SF-12), however, did not differ across groups. Individuals with impaired bowel and bladder control reported lower quality of life on several domains compared with those with independent control of bowel and bladder. Though the two groups did not differ in self-reported social integration, dependent individuals may have greater difficulty creating new social relationships.


Matrix mineralization in MC3T3-E1 cell cultures initiated by beta-glycerophosphate pulse.
MC3T3-E1 cells, grown in the presence of serum and ascorbate, express alkaline phosphatase and produce an extensive collagenous extracellular matrix that can be mineralized by the addition of beta-glycerophosphate (beta-GP). In the present work, we study the influence of concentration and duration of beta-GP treatment on the mineralization pattern in 4-week-old cell cultures. Amount and structure of mineral deposition were monitored by von Kossa staining, light, and electron microscopy, as well as small-angle X-ray scattering (SAXS) of unstained specimens. SAXS measures the total surface of the mineral phase and is therefore preferentially sensitive to very small crystals (typically <50 nm). It was used to determine the ratio (M) of small crystals to collagen matrix. A variety of mineralization patterns was observed to occur simultaneously, some associated with collagen within nodules or in deeper layers of the cultures and some independent of it. At a beta-GP concentration of 10 mmol, mineralization was initiated after about 24 h and continued to increase, irrespective of whether the high level of beta-GP was maintained or reduced to 2 mmol. With shorter pulses (<24 h), no significant mineralization was observed in the week following beta-GP pulse. With continuous treatment at 5 mmol beta-GP, the first signs of mineralization were detected 14 days after the beginning of treatment in the 4-week-old cultures, but no mineralization at all occurred at lower beta-GP concentrations. When cells were grown without ascorbic acid for 4 weeks, only two cell layers without collagen matrix were found. In these cultures, no mineralization detectable by SAXS could be induced with beta-GP. These data indicate that, in viable cells, high doses of beta-GP are essential for the nucleation of mineral crystals, but not for the progression of mineralization once crystals had been nucleated. In contrast, when 4-week-old cell cultures were devitalized, M was found to increase immediately, even at 2 mmol beta-GP. These results suggest that, in MC3T3-E1 cell cultures, cell viability is essential for prevention of spontaneous mineralization of the extracellular matrix.


Human papillomavirus-16 and -18 replication in esophagus squamous cancer cell lines does not require heterologous E1 and E2 proteins.
Human papillomaviruses (HPVs) are double-stranded DNA viruses that replicate in the nuclei of squamous epithelial cells. HPVs can be classified into high-risk (e.g., types 16, 18, 31, and 33) or low-risk (e.g., types 6, 11, and 30), depending on their association with benign or malignant tumors. We recently described the association of HPV-16 and -18 with esophagus squamous cell cancer. HPV replication was studied in representative cell lines derived from esophagus cancers. HPV-16 and -18 genomes were independently transiently transfected into HCE-4 and HCE-7 cell lines with and without E1 and E2 genes under heterologous promoters. Southern blot analysis demonstrated that these cell lines support viral replication. However, heterologous E1 and E2 are not required for HPV replication. These findings suggest that specific host nuclear factors in esophageal squamous epithelial cells may support HPV replication.


Nonsuicidal self-injury in undergraduate students: a cross-sectional study and association with suicidal behavior.
The objective of this study was to investigate nonsuicidal self-injury (NSSI) in graduates and correlate NSSI with sociodemographic profile, suicidal behavior, and prior mental health disorders. The study is part of a larger survey investigating sociodemographic profile, quality of life and mental health in undergraduates from one of Brazil´s largest universities. A bespoke questionnaire was devised about NSSI based on the DSM5 diagnostic criteria. The data were analyzed using the statistical analysis package SPSS. A total of 6.906 university students took part in the study. Regarding NSSI, 17.8% of students reported at least one episode in their lifetime, and 35% reported age at NSSI onset of 14-16 years. Self-injurious behavior was associated with female gender, self-reported black skin color, dissatisfaction with the chosen course, history of bullying and prior mental disorder. There was a ten times greater risk of suicidal behavior among self-injurers and this risk was higher still for recurrent NSSI.


Functional Status After Transcatheter and Surgical Aortic Valve Replacement: 2-Year Analysis From the SURTAVI Trial.
This study sought to evaluate patient-centered metrics in intermediate-surgical-risk aortic stenosis patients enrolled in the SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial treated with self-expanding transcatheter aortic valve replacement (TAVR) or surgery. Studies have shown TAVR to be an alternative to surgery in patients with severe symptomatic aortic stenosis but have focused on "hard endpoints," including all-cause mortality and stroke, rather than on comparative patient-centered metrics, such as functional status and symptom burden. The study analyzed functional status (6-minute walk test [6MWT]) and symptom burden (Kansas City Cardiomyopathy Questionnaire) in 1,492 patients from the SURTAVI trial at baseline, 30 days, 1 year, and 2 years. Patients were categorized by baseline functional status into tertiles of slow, medium, and fast walkers. Patients with lowest capacity baseline functional status were commonly women, had higher Society of Thoracic Surgeons scores, and had more New York Heart Association functional class III or IV symptoms; reduced baseline functional status was associated with higher aortic valve- and heart failure-related hospitalization at 2 years. There was greater improvement in 6MWT distance in TAVR compared with surgery patients at 30 days (P < 0.001) and 1 year (P = 0.012), but at 2 years, both groups had similar improvement (P = 0.091). The percentage of patients with large improvement in 6MWT was greatest in patients categorized as slow walkers and lowest in fast walkers. Symptom burden improved after TAVR at 30 days and after both procedures at 1 and 2 years. In this substudy of patients from the SURTAVI trial, patients receiving TAVR demonstrated a more rapid improvement in functional status and symptom burden compared with patients undergoing surgery; however, both groups had similar improvements in long-term follow-up. (Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Severe, Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement [SURTAVI]; NCT01586910).


Plasmacytoma of the uvea in a case of multiple myeloma.
A case of plasmacytoma in the uvea, both clinically and grossly anatomically mimicking a malignant melanoma, is described in a 63-year-old man who died from multiple myeloma. This is an extremely rare condition in the eye. Only one report of a similar tumour has been found in the literature.


Facile Synthesis of g-C3N4/TiO2/Hectorite Z-Scheme Composite and Its Visible Photocatalytic Degradation of Rhodamine B.
A novel g-C3N4/TiO2/hectorite Z-scheme composites with oxygen vacancy (Vo) defects and Ti3+ were synthesized by so-gel method and high temperature solid phase reaction. This composite exhibited high visible photo-catalytic degradation of rhodamine B (RhB). The apparent rate constant of g-C3N4/TiO2/hectorite was 0.01705 min-1, which is approximately 5.38 and 4.88 times that of P25 and g-C3N4, respectively. The enhancement of photo-catalytic efficiency of the composites can be attributed to the great light harvesting ability, high specific surface area and effective separation of electrons(e-) and holes(h+). The F element from Hectorite causes the formation of Vo and Ti3+ in TiO2, making it responsive to visible light. The effective separation of e- and h+ mainly results from Z-scheme transfer of photo-produced electrons in g-C3N4/TiO2 interface. The composites can be easily recycled and the degradation rate of the RhB still reached 84% after five cycles, indicating its good reusability.


Contents in tumor-educated platelets as the novel biosource for cancer diagnostics.
Liquid biopsy, a powerful non-invasive test, has been widely used in cancer diagnosis and treatment. Platelets, the second most abundant cells in peripheral blood, are becoming one of the richest sources of liquid biopsy with the capacity to systematically and locally respond to the presence of cancer and absorb and store circulating proteins and different types of nucleic acids, thus called "tumor-educated platelets (TEPs)". The contents of TEPs are significantly and specifically altered, empowering them with the potential as cancer biomarkers. The current review focuses on the alternation of TEP content, including coding and non-coding RNA and proteins, and their role in cancer diagnostics.


Highly accurate and consistent method for prediction of helix and strand content from primary protein sequences.
One of interesting computational topics in bioinformatics is prediction of secondary structure of proteins. Over 30 years of research has been devoted to the topic but we are still far away from having reliable prediction methods. A critical piece of information for accurate prediction of secondary structure is the helix and strand content of a given protein sequence. Ability to accurately predict content of those two secondary structures has a good potential to improve accuracy of prediction of the secondary structure. Most of the existing methods use composition vector to predict the content. Their underlying assumption is that the vector can be used to provide functional mapping between primary sequence and helix/strand content. While this is true for small sets of proteins we show that for larger protein sets such mapping are inconsistent, i.e. the same composition vectors correspond to different contents. To this end, we propose a method for prediction of helix/strand content from primary protein sequences that is fundamentally different from currently available methods. Our method is accurate and uses a novel approach to obtain information from primary sequence based on a composition moment vector, which is a measure that includes information about both composition of a given primary sequence and the position of amino acids in the sequence. In contrast to the composition vector, we show that it provides functional mapping between primary sequence and the helix/strand content. A set of benchmarks involving a large protein dataset consisting of over 11,000 protein sequences from Protein Data Bank was performed to validate the method. Prediction done by a neural network had average accuracy of 91.5% for the helix and 94.5% for the strand contents. We also show that using the new measure results in about 40% reduction of error rates when compared with the composition vector results. The developed method has much better accuracy when compared with other existing methods, as shown on a large body of proteins, in contrast to other reported results that often target small sets of specific protein types, such as globular proteins.


Changes in the adrenal cortex of the rat after chronic administration of the steroidogenic inhibitor U-8113.
In concert with studies of the effects of various pharmacologic inhibitors of corticosteroidogenesis on adrenocortical morphology, U-8113, an analog of amphenone B, was administered daily to Sprague-Dawley rats for 7, 14, 21 or 30 day. The primary morphological responses involved increases in adrenal weight, width of zona fasciculata, width of zona reticularis, intracellular lipids, mitochondrial size, mitochondrial vacuolation and crystalline-like inclusions, small coated vesicles, lysosomes, autophagic vacuoles and cholesterol ester clefts. In particular, the increases in lysosomes, coated vesicles and autophagic vacuoles containing morphologically altered mitochondria were considered reflective of mechanisms designed to maintain cellular integrity amidst functional impairment. Lipid analysis revealed marked increases in cholesterol esters and phospholipids, supportive of morphological observations. When permitted a 14 day recovery period following either 14 or 30 days of inhibitor therapy, most fine structural alterations and lipid derangements were diminished, and the cells approximated normal parameters.


Determination of critical concentration for drug susceptibility testing of Mycobacterium tuberculosis against para-aminosalicylic acid with clinical isolates with thyA, folC and dfrA mutations.
Accurate determination of antimicrobial resistance profiles is of great importance to formulate optimal regimens against multidrug-resistant tuberculosis (MDR-TB). Although para-aminosalicylic acid (PAS) has been widely used clinically, the reliable testing methods for PAS susceptibility were not established. Herein, we aimed to establish critical test concentration for PAS on the Mycobacterial Growth Indicator Tube (MGIT) 960 in our laboratory settings. A total of 102 clinical isolates were included in this study, including 82 wild-type and 20 resistotype isolates. Minimum inhibitory concentration (MIC) was determined by MGIT 960. Whole-genome sequencing was used to identify the mutation patterns potentially conferring PAS resistance. Sequence alignment and structure modelling were carried out to analyze potential drug-resistant mechanism of folC mutant. Overall, the Minimum inhibitory concentration (MIC) distribution demonstrated excellent separation between wild-type and resistotype isolates. The wild-type population were all at least 1 dilution below 4 μg/ml, and the resistotype population were no lower than 4 μg/ml, indicating that 4 μg/ml was appropriate critical concentration to separate these two populations. Of 20 mutant isolates, 12 (60.0%) harbored thyA mutations, 2 (10%) had a mutation on upstream of dfrA, and the remaining isolates had folC mutations. Overall, thyA and folC mutations were scattered throughout the whole gene without any one mutation predominating. All mutations within thyA resulted in high-level resistance to PAS (MIC > 32 μg/ml); whereas the MICs of isolates with folC mutations exhibited great diversity, ranged from 4 to > 32 μg/ml, and sequence and structure analysis partially provided the possible reasons for this diversity. We propose 4 μg/ml as tentative critical concentration for MGIT 960. The major mechanism of PAS resistance is mutations within thyA and folC in MTB isolations. The whole-gene deletion of thyA locus confers high-level resistance to PAS. The diversity of many distinct mutations scattered throughout the full-length folC gene challenges the PCR-based mutation analysis for PAS susceptibility.


[Study on pharmacokinetics of oridonin in mice].
To develop a HPLC method for the determination of plasma concentration of oridonin (ORI) and study the pharmacokinetics of ORI in mice. Blood was sampled from mice which were injected ORI by 10 mg x kg(-1) at different time intervals, and the concentration of ORI was determined by HPLC. The pharmacokinetic parameters were accessed by 3P97. The calibration curve was linear (r = 0.998 7) within the range of 0.202-20.0 mg x L(-1) for ORI in plasma. The average recoveries were more than 93%. The within-day and between-day precisions were no more than 9%. After i.v. oridonin in mice, the plasma concentration-time course fitted well to two-compartment model. The pharmacokinetic equation was C = 16.192 5e(-0.554 6t) + 5.475 7e(-0.016 3t). The pharmacokinetic parameters were below: t1/2alpha 1.249 9 min, t1/2beta 42.638 4 min, K21 0.152 3 min(-1), K12 0.359 3 min(-1), K10 0.0592 min(-1), AUC 366.035 0 microg x min x mL(-1), CL 0.0273 L x min(-1) x kg(-1), V(c)0.461 5 L x kg(-1). The method can be used to determine the concentration and to investigate the pharmacokinetics of ORI in mice. ORI was absorbed and distributed very fast in mice. The effect of ORI was rapid. The elimination was the main process.


Ligand-Promoted RhI -Catalyzed C2-Selective C-H Alkenylation and Polyenylation of Imidazoles with Alkenyl Carboxylic Acids.
The first RhI -catalyzed, directed decarbonylative C2-H alkenylation of imidazoles with readily available alkenyl carboxylic acids is reported. The reaction proceeds in a highly regio- and stereoselective manner, providing efficient access to C2-alkenylated imidazoles that are generally inaccessible by known C-H alkenylation methods. This transformation accommodates a wide range of alkenyl carboxylic acids, including challenging conjugated polyene carboxylic acids, and diversely decorated imidazoles with high functional group compatibility. The presence of a removable pyrimidine directing group and the use of a bidentate phosphine ligand are pivotal to the success of the catalytic reaction. This process is also suitable for benzimidazoles. Importantly, the scalability and diversification of the products highlight the potential of this protocol in practical applications. Detailed experimental and computational studies provide important insights into the underlying reaction mechanism.


Rapid micromethod for the analysis of mitotane and its metabolite in plasma by gas chromatography with electron-capture detection.
A rapid micromethod for 50-microliter samples is described for the analysis in plasma of mitotane (o,p'-DDD) and its metabolite (o,p'-DDE), using p,p'-DDD as internal standard. The compounds are extracted with heptane without sample pretreatment, and an aliquot is directly analysed by gas chromatography with electron-capture detection. Absolute recoveries for all three compounds were ca. 87% and coefficients of variation were less than 5%. The method is being used successfully for monitoring patients with Cushing's syndrome who receive chronic oral mitotane therapy.


Modified oleic cottonseeds show altered content, composition and tissue-specific distribution of triacylglycerol molecular species.
Targeted increases in monounsaturated (oleic acid) fatty acid content of refined cottonseed oil could support improved human nutrition and cardiovascular health. Genetic modifications of cottonseed fatty acid composition have been accomplished using several different molecular strategies. Modification of oleic acid content in cottonseed embryos using a dominant-negative protein approach, while successful in effecting change in the desired fatty acid composition, resulted in reduced oil content and seed viability. Here these changes in fatty acid composition were associated with changes in dominant molecular species of triacylglycerols (TAGs) and their spatial distributions within embryo tissues. A combination of mass spectrometry (MS)-based lipidomics approaches, including MS imaging of seed cryo-sections, revealed that cotton embryos expressing a non-functional allele of a Brassica napus delta-12 desaturase showed altered accumulation of TAG species, especially within cotyledonary tissues. While lipid analysis of seed extracts could demonstrate detailed quantitative changes in TAG species in transgenics, the spatial contribution of metabolite compartmentation could only be visualized by MS imaging. Our results suggest tissue-specific differences in TAG biosynthetic pathways within cotton embryos, and indicate the importance of considering the location of metabolites in tissues in addition to their identification and quantification when developing a detailed view of cellular metabolism.


Management of Common Postoperative Infections in the Surgical Intensive Care Unit.
Postoperative infection and sepsis in the surgical intensive care unit (SICU) are common problems, and can be the reason for SICU admission or can be acquired during the SICU stay. Both diagnosis and management of infection and sepsis in the SICU can be complex, related to the surgical procedures performed, patient comorbidities, and resistant pathogens. The need for "source control" of postoperative infections can pose specific challenges and significant complexity in patient management. Postoperative infections in the SICU are associated with increased morbidity, mortality, and resource utilization, and therefore a strong focus on infection preventive strategies is warranted.


Mouse 89 kD heat shock protein. Two polypeptides with distinct developmental regulation.
Unstressed early mouse embryos have been previously shown [1] to synthesize at very high rates 70 and 89 kD proteins belonging to the heat shock protein (HSP) family. But it was not clear whether expression of heat shock-inducible or non-inducible (cognate) genes accounted for this spontaneous synthesis. In this report we show that the 89 kD mouse HSP can be separated into two proteins by high resolution PAGE. These two components show distinct but related peptide pattern after limited proteolysis. They are synthesized from distinct mRNAs. One of these proteins--HSP89f--is synthesized at a high rate by unstressed cells and its synthesis is rather insensitive to stress, whereas synthesis of the other protein--HSP89s--is strongly stimulated by heat shock in fibroblasts. Both HSP89f and HSP89s are major proteins synthesized in unstressed mouse preimplantation embryos and embryonal carcinoma (EC) cells. After in vitro differentiation of the EC cells the spontaneous synthesis of HSP89s decreases. Thus spontaneous expression of a mammalian inducible HSP is developmentally regulated.


Binding and isolation of tumor cells in biological media with perfluorocarbon microbubbles.
With the emerging interest in personalized medicine, there is strong demand for new technologies for clinical sample interrogation. Exfoliated tumor cells in variety of pathological samples (e.g., blood, bone marrow, urine) could provide invaluable information for diagnosis and prognosis of cancers. Here we describe a detailed method for capture and isolation of tumor cells in medium, blood, or large issue buffy coat using EpCAM-targeted buoyant microbubbles (MBs). Perflorohexane gas lipid shell MBs were prepared with emulsification method and conjugated with antibody as described by us before [25]. The binding of EpCAM-targeted MBs to A549 (human lung carcinoma) and 4T1 (mouse breast carcinoma) cells spiked into BSA/PBS or blood was more than 90%, which was comparable with commercial anti-EpCAM immunomagnetic beads (DynaBeads). Anti-EpCAM MBs efficiently (75-82%) isolated BxPC3 pancreatic tumor cells spiked into medium, blood or a buffy coat, within 15-30 min of incubation. We discuss MB parameters and experimental conditions critical to achieve efficient cells binding and isolation. In conclusion, MB-assisted cell isolation is a promising method for rapid enrichment of cells and biomarkers from biological samples.


Influence of visual deprivation on the visual and oculomotor system: acetylcholinesterase activity in oculomotor neurons.
The effects of visual deprivation (dark-rearing) on neurons in both the visual and oculomotor systems of black mice were studied using morphologic and histochemical techniques. In the neurons of the dorsal nucleus of the lateral geniculate body, the cytoplasm of dark-reared mice was less developed and the cytoplasm/nucleus ratio was significantly smaller in the dark-reared mice than in the controls. In contrast, large motoneurons in the oculomotor nucleus did not show any ultrastructural changes and the cytoplasm/nucleus ratio was normal. However, in large motoneurons of dark-reared mice, acetylcholinesterase (AChE)-positive areas were scattered in the cytoplasm, and the ratio of the AChE-positive areas to the cytoplasm area was significantly smaller than that in the controls.


Ultralight and robust aerogels based on nanochitin towards water-resistant thermal insulators.
The development of lightweight, strong and high-performance thermal insulators from renewable biomass are highly desired for sustainable development. Here, ultralight aerogels based on renewable nanochitin with outstanding mechanical properties, excellent water-resistant, and promising thermal insulation properties are fabricated. The pristine nanochitin aerogels (PNCAs) assembled from mechanically strong carboxylated chitin nanorods are firstly prepared through acid-induced gelation and supercritical drying. The resultant PNCAs present tunable density (10-50 mg/cm3) and strong mechanical stiffness (the specific compression modulus of 30.2 MPa cm3/g) combining with low thermal conductivity (27.2 mW/m K). After a facile silylation modification, the silylated nanochitin aerogels (SNCAs) exhibit hydrophobic behavior (contact angle >130°), improved compression performance (the specific compression modulus of 65 MPa cm3/g), and promising thermal insulation property (30.5-35.8 mW/m K). Moreover, the silylated aerogel shows a negligible loss of mechanical performance when exposed to water for 12 h at 35 °C.


Interventions to Improve Surveillance for Hepatocellular Carcinoma in High-Risk Patients: A Scoping Review.
Hepatocellular carcinoma (HCC) is most often a sequela of chronic liver disease or chronic hepatitis B infection. Among high-risk patients, surveillance for HCC every 6 months is recommended by international guidelines. However, rates of HCC surveillance are suboptimal (11-64%). Barriers at the patient, provider, and healthcare delivery system levels have been identified. We performed a systemic scoping review to identify and characterize interventions to improve HCC surveillance that has previously been evaluated. Searches using key terms in PubMed and Embase were performed to identify studies examining interventions designed to improve the surveillance rate for HCC in patients with cirrhosis or chronic liver disease that were published in English between January 1990 and September 2021. Included studies (14) had the following study designs: (1) randomized clinical trials (3, 21.4%), (2) quasi-experimental (2, 14.3%), (3) prospective cohort (6, 42.8%), and (4) retrospective cohort (3, 21.4%). Interventions included mailed outreach invitations, nursing outreach, patient education with or without printed materials, provider education, patient navigation, chronic disease management programs, nursing-led protocols for image ordering, automated reminders to physicians and nurses, web-based clinical management tools, HCC surveillance databases, provider compliance reports, radiology-led surveillance programs, subsidized HCC surveillance, and the use of oral medications. It was found that HCC surveillance rates increased after intervention implementation in all studies. Despite improvements in HCC surveillance rates with intervention, compliance remained suboptimal. Further analysis of which interventions yield the greatest increases in HCC surveillance, design of multi-pronged strategies, and improved implementation are needed.


Identification of the STAT1 gene and the characterisation of its immune response to immunostimulants, including nervous necrosis virus (NNV) infection, in Malabar grouper (Epinephelus malabaricus).
Signal Transducer and Activator of Transcription (STAT)-1 is an indispensable signal transduction protein that is involved in the interferon pathway. STAT-1 plays an important role in the innate immune response. The full-length cDNA of Malabar grouper (Epinephelus malabaricus) STAT-1, MgSTAT1, was cloned. Phylogenetic analysis was performed based on the amino acid sequence. Our results indicate that STAT1 is highly conserved with other vertebrates. We also report the expression of MgSTAT1 in different tissues treated with immune stimulants, including LPS, CpG ODN, and poly (I:C), in vivo. The expression of MgSTAT1 was significantly induced in the head kidney upon treatment with poly (I:C) compared to the control. Moreover, the results indicate that MgSTAT1 is up-regulated during nervous necrosis virus (NNV) infection. This study reveals that similar to the mammalian antiviral response, MgSTAT1 mediates the immune response in Malabar grouper.


Machine learning algorithms to predict major adverse cardiovascular events in patients with diabetes.
Major Adverse Cardiovascular Events (MACE) are common complications of type 2 diabetes mellitus (T2DM) that include myocardial infarction (MI), stroke, and heart failure (HF). The objective of the current study was to predict MACE among T2DM patients. Type 2 diabetes mellitus patients above 18 years old were recruited for the study from the All of Us Research Program. Eligible participants were those who took sodium-glucose cotransporter 2 inhibitors. Different Machine learning algorithms: including RandomForest (RF), XGBoost, logistic regression (LR), and weighted ensemble model (WEM) were employed. Clinical attributes, electrolytes and biomarkers were explored in predicting MACE. The feature importance was determined using mean decrease accuracy. Overall, 9, 059 subjects were included in the analyses, of which 5197 (57.4%) were females. The XGBoost Model demonstrated a prediction accuracy of 0.80 [0.78-0.82], which is higher as compared to the RF 0.78[0.76-0.80], the LR model 0.65 [0.62-0.67], and the WEM 0.75 [0.73-0.76], respectively. The classification accuracy of the models for stroke was more than 95%, which was higher than prediction accuracy for MI (∼85%), and HF (∼80%). Phosphate, blood urea nitrogen and troponin levels were the major predictors of MACE. The ML models had shown acceptable performance in predicting MACE in T2DM patients, except the LR model. Phosphate, blood urea nitrogen, and other electrolytes were important predictors of MACE, which is consistent between the individual components of MACE, such as stroke, MI, and HF. These parameters can be calibrated as prognostic parameters of MACE events in T2DM patients.


The injectable neurostimulator: an emerging therapeutic device.
Injectable neurostimulators are currently applied in clinical trials to minimize the side effects such as discomfort, risk of infection, and post-surgery trauma, which can be pronounced with conventional, bulky implantable neurostimulators. Owing to its smaller size, wireless-updatable software, and wireless power supply, the injectable neurostimulator is presumably less invasive, 'smarter', and has a longer lifetime. We discuss the concept and development of the injectable neurostimulator, persistent implementation challenges, and obstacles to be overcome in its evolution. We survey the use of new materials, technologies, and design methods for injectable electrodes, batteries, antennas, and packaging to enhance reliability and other features. These advances in the field are accompanied by progress in electrophysiology, neuroscience, neurology, clinical trials, and treatments.


Down-regulation of EGFR prolonged cell growth of glioma but did not increase the sensitivity to temozolomide.
Malignant glioma is an invasive disease of the central nervous system. One of the factors that regulate growth of these tumors is expression of epidermal growth factor receptor (EGFR) in the cells. This study investigated the effects of down-regulation of EGFR on cell proliferation, cell cycle and cytotoxicity to antineoplastic agent. A short hairpin RNA transcription vector targeting EGFR was transfected into KNS42 cells. Growth curve, cell cycle and sensitivity to temozolomide of the cells were assessed. Transfection inhibited EGFR expression by 50.5%. It prolonged cell doubling time by 25.7%. However, it did not meaningfully alter the cell cycle populations nor increase sensitivity to temozolomide. Suppressing expression of EGFR inhibited cell proliferation. However, unlike PTEN expression or ROCK1 down-regulation, it did not alter the cell cycle or increase sensitivity to temozolomide.


Mesenchymal stromal cells for sepsis and septic shock: Lessons for treatment of COVID-19.
Sepsis is defined as life-threatening organ dysfunction caused by a deregulated immune host response to infection. The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted this multifactorial and complex syndrome. The absence of specific treatment neither against SARS-CoV-2 nor against acute respiratory distress syndrome (ARDS), the most serious stage of this infection, has emphasized the need to find alternative treatments. Several therapeutics are currently being tested, including mesenchymal stromal cells. These cells, already used in preclinical models of ARDS, sepsis, and septic shock and also in a few clinical trials, appear well-tolerated and promising, but many questions remain unanswered.


Hypoglycin stimulates insulin secretion.
Hypoglycin A(0.01--1.0 mmol/l) stimulated insulin release from pieces of rabbit pancreas in vitro in the presence or absence of extracellular glucose. The relevance of this finding to the hypoglycaemia of Jamaican vomiting sickness is discussed.


Characterization of an Amorphous Titanium Oxide Film Deposited onto a Nano-Textured Fluorination Surface.
The photocatalytic activity of an amorphous titanium oxide (a-TiOx) film was modified using a two-step deposition. The fluorinated base layer with a nano-textured surface prepared by a selective fluorination etching process acted as growth seeds in the subsequent a-TiOx deposition. A nanorod-like microstructure was achievable from the resulting a-TiOx film due to the self-assembled deposition. Compared to the a-TiOx film directly deposited onto the untreated base layer, the rate constant of this fluorinate-free a-TiOx film surface for decomposing methylene blue (MB) solution that was employed to assess the film's photocatalytic activity was markedly increased from 0.0076 min-1 to 0.0267 min-1 as a mechanism for the marked increase in the specific surface area.


Bax inhibitor-1 regulates the expression of P450 2E1 through enhanced lysosome activity.
In this study, we explored the role of Bax inhibitor-1 (BI-1) on the expression of P450 2E1 and related ROS production. P450 2E1 protein, not mRNA, was expressed at relatively low levels in BI-1 plasmid-transfected cells (BI-1 cells) compared with neomycin-resistant vector-transfected cells (Neo cells). When exposed to ER stress, P450 2E1 expression and activity and ER membrane lipid peroxidation increased in both Neo cells and BI-1 cells, but to a lesser degree in BI-1 cells. This observation correlated with the lower level of ER stress in BI-1 cells than Neo cells. To examine the BI-1-associated P450 2E1 degradation mechanism, cells were treated with the lysosome inhibitor, bafilomycin and the proteasome inhibitor, MG132. Bafilomycin recovered the reduced P450 2E1 expression in BI-1 cells, but did not affect P450 2E1 expression in Neo cells. Next, proteosomal and lysosomal activities in Neo cells were compared to those in BI-1 cells. Although proteosomal activity was similar between Neo and BI-1 cells, LysoTracker and acridine orange labeling, lysosomal V-ATPase activity, and lysosomal cathepsin B expression were higher in BI-1 cells than in Neo cells. In the presence of ER stress, lysosomal activities decreased in Neo cells but did not change in BI-1 cells. P450 2E1 expression and ER membrane lipid peroxidation were greater in the hepatocytes and livers of BI-1 knock-out mice than in BI-1 wild-type cells and mice. Our results suggest that the BI-1-mediated enhancement of lysosomal activity regulates P450 2E1 expression and resultant ROS accumulation.


In situ assay with the midge Kiefferulus calligaster for contamination evaluation in aquatic agro-systems in central Thailand.
The aims of this study were to verify the suitability of in situ tests using the tropical midge Kiefferulus calligaster and to evaluate the most sensitive endpoint for the assessment of aquatic pesticide contamination. In situ tests were carried out in freshwater drainage channels (farm channels) that supply vegetable crops and receive considerable pesticide spray drift, and at channels outside farms (main channels). Moreover a pesticide-free farm was used as reference site. The endpoints analysed were: survival of the larvae, body length increment, capsule width increment, cholinesterase activity and glutathione S-transferase activity. Seasonal change was investigated as rainy season and dry season. Deleterious effects were observed at some farms especially during the rainy season when farmers apply heavier doses of pesticides. However, high mortality rates observed in main channels suggest that these water bodies are also affected by other impacts besides pesticide use. This work shows the potential of the in situ assay with K. calligaster as a tool for the environmental quality assessment of tropical aquatic ecosystems.


The Importance of Extensional Rheology in Bolus Control during Swallowing.
Thickened fluids are commonly used in the medical management of individuals who suffer swallowing difficulty (known as dysphagia). Previous studies have shown that the rheological properties of a liquid affect the flow behavior of the bolus in swallowing, such as pharyngeal transit time. While there is no doubt that shear rheology is a highly important factor for bolus flow, it is suspected that extensional properties of a liquid bolus also plays an important role in swallowing, due to elongation of the bolus as it flows through the oropharynx. Our aim in this work was to observe the effect of extensional viscosity on pharyngeal transit time and elongation of the bolus during swallowing. Eight samples of thickened liquid barium that were shear-controlled, but varied in extensional viscosity and two samples that were extensional-controlled, but varied in shear viscosity were swallowed by eight healthy individuals. Data were collected under lateral view of videofluoroscopy swallow study (VFSS); measures of pharyngeal transit time and the ratio of the length to the width of the bolus on the frame of Upper Esophageal Sphincter (UES) opening were taken from the VFSS recordings. It was observed that the pharyngeal transit time generally increases when the fluids are thickened to higher IDDSI consistency. Additionally, higher extensional viscosity fluids reduced the elongation of the bolus during swallowing, thus potentially reducing the risk of post-swallow residue due to bolus breakage. This study confirmed the relevance of the extensional viscosity of the bolus in swallowing.


Immunochemical properties of oligosaccharide-protein conjugates with Klebsiella-K2-specificity. II. Protective capacity of the conjugates and anti-conjugate antibodies against infection with Klebsiella pneumoniae 01:K2 in mice.
Oligosaccharide subunits from Klebsiella pneumoniae B5055 capsular polysaccharide, covalently linked to protein carriers, the native polysaccharide, and killed whole bacteria, were compared with respect to their immunogenicity in mice and their capacity to protect mice against bacterial infection. The protection was studied (a) by active immunization and (b) by passive administration of antisera raised in rabbits using the different immunogens. The results were as follows: in the active protection experiments the octa- and dodecasaccharide conjugates were as effective as the polysaccharide in increasing the LD50 by a factor of 10(5) as compared to nonimmunized animals. Thus, these antigens were only slightly less effective than killed bacteria. In contrast the tetrasaccharide conjugate was at least 1000-fold less effective than all other antigens used. In the passive protection experiments these results were paralleled in that the antiserum against the tetrasaccharide conjugate also showed the lowest degree of protection, though, for methodical reasons, the differences in the LD50s were less pronounced. The drastically lower efficiency of the tetrasaccharide in comparision to its higher oligomers is in agreement with serological findings previously published (see first communication), which showed that two repeating units are the minimum requirement for a substantial representation of polysaccharide serological specificity.


A compound plant extract and its antibacterial and antioxidant properties in vitro and in vivo.
The present study was conducted to prepare a compound plant extract as a candidate animal feed additive. Firstly, Evodia rutaecarpa (ER), Schisandra sphenanthera (SS), Punica granatum (PG) and Artemisia argyi (AA) were screened out from 17 plants as materials of candidate compound plant extracts by measuring the antibacterial rate on Escherichia coli and Salmonella paratyphoid, and the scavenging capability on 2,2 diphenyl-1-picrylhydrazine radical in vitro. Secondly, proportions of the four materials were optimized with an L9 (43) orthogonal experiment. By range analysis of experimental results, two compound extracts (named as F1 and F2) with the strongest antibacterial and antioxidant functions were obtained. The ratio of ER: SS: PG: AA is 9:9:1:3 in F1 and 9:9:9:3 in F2, respectively. Finally, the effects of F1 and F2 on security and efficacy in vivo were evaluated. In healthy mice, F1 had no significant effects (p > 0.05) on all blood parameters and viscera indices, and at 1000 mg/kg bw dose significantly increased (p < 0.05) the average daily gain (ADG). F2 decreased (p < 0.05) white blood cell count at 3000 mg/kg bw and increased (p < 0.05) red blood cell count at 333 mg/kg bw. In immunosuppressed mice, both F1 and F2 improved ADG (p < 0.05) and the feed intake to gain ratio (p < 0.01), and increased the activities of hepatic superoxide dismutase (p < 0.05), catalase (p < 0.05) and total antioxygen capacity (p < 0.05), and the content of malonaldehyde (p < 0.01). In mice challenged with Escherichia coli, the antidiarrhea and reducing mortality effects of F1 were equivalent to the antibiotic. F2 failed to protect the experimental mice. These results suggested F1, a compound plant extract, show a great potential as a substitute for antibiotics in animal feed.


A note on removal of the compaction effect for the 210Pb method.
The compaction effect may significantly flatten an excess (210)Pb depth profile near the sediment-water interface, resulting in erroneous (210)Pb dating. There are three mathematical approaches to correct for the compaction effect. In the present paper, some further deductions have been done to make the procedure of approach calculations more clearly and practically. Meanwhile, the three approaches are also compared using a case study selected from the literature.


Amino-terminal fragments of mutant huntingtin show selective accumulation in striatal neurons and synaptic toxicity.
Huntington disease (HD) is caused by expansion of a glutamine repeat in the amino-terminal region of huntingtin. Despite its widespread expression, mutant huntingtin induces selective neuronal loss in striatal neurons. Here we report that, in mutant mice expressing HD repeats, the production and aggregation of N-terminal huntingtin fragments preferentially occur in HD-affected neurons and their processes and axonal terminals. N-terminal fragments of mutant huntingtin form aggregates and induce neuritic degeneration in cultured striatal neurons. N-terminal mutant huntingtin also binds to synaptic vesicles and inhibits their glutamate uptake in vitro. The specific processing and accumulation of toxic fragments of N-terminal huntingtin in HD-affected striatal neurons, especially in their neuronal processes and axonal terminals, may contribute to the selective neuropathology of HD.


Protein Synthesis in Sub-Micrometer Water-in-Oil Droplets.
Water-in-oil (w/o) emulsions are used as a cellular model because of their unique cell-like architecture. Previous works showed the capability of eukaryotic-cell-sized w/o droplets (5-50 μm) to support protein synthesis efficiently; however data about smaller w/o compartments (<1 μm) are lacking. This work focuses on the biosynthesis of the enhanced green fluorescent protein (EGFP) inside sub-micrometric lecithin-based w/o droplets (0.8-1 μm) and on its dependence on the compartments' dynamic properties in terms of solute exchange mechanisms. We demonstrated that protein synthesis is strongly affected by the nature of the lipid interface. These findings could be of value and interest for both basic and applied research.


Hematopoietic stem cell transplant in two pediatric patients testing positive for SARS-CoV-2: A case report.
The SARS-CoV-2 pandemic brought challenges to all areas of medicine. In pediatric bone marrow transplant (BMT), one of the biggest challenges was determining how and when to transplant patients infected with SARS-CoV-2 while mitigating the risks of COVID-related complications. Our joint adult and pediatric BMT program developed protocols for performing BMT during the pandemic, including guidelines for screening and isolation. For patients who tested positive for SARS-CoV-2, the general recommendation was to delay BMT for at least 14 days from the start of infection and until symptoms improved and the patient twice tested negative by polymerase chain reaction (PCR). However, delaying BMT in patients with malignancy increases the risk of relapse. We opted to transplant two SARS-CoV-2 persistently PCR positive patients with leukemia at high risk of relapse. One patient passed away early post-BMT of a transplant-related complication. The other patient is currently in remission and doing well. These cases demonstrate that when the risk associated with delaying BMT is high, it may be reasonable to proceed to transplant in pediatric leukemia patients infected with SARS-CoV-2.