Nonaromatic hydroxylation of bupivacaine during continuous epidural infusion in man.
Less than 11% of the dose of bupivacaine could be accounted for in urine from 10 patients receiving continuous epidural infusions. HPLC analysis of metabolites confirmed (S)-bupivacaine was more extensively metabolised than (R)-bupivacaine, and dealkylation was the predominant metabolic pathway although co-elution of metabolites made quantitation difficult. The percentage of (S)-2',6'-pipecoloxylidide and co-eluting metabolites excreted relative to (R)-2',6'-pipecoloxylidide from three patients was 0.32+/-0.05, while for seven patients it was 1.28+/-0.09. Conversely, the percentage of (S)-3'-hydroxy bupivacaine and co-eluants excreted relative to (R)-2',6'-pipecoloxylidide from the three patients (1.76+/-0.48) was greater than the seven patients (0.19+/-0.09). Urinary metabolites were analysed for evidence of aliphatic hydroxylation of bupivacaine. Chiral liquid chromatography-mass spectrometry (LC-MS) on an alpha(1)-glycoprotein column at pH 7 used hydroxylamine acetate as the volatile mobile phase. Compounds tentatively identified as hydroxybupivacaines by MRM were verified by their product ion spectra in a subsequent MS-MS run. Eighteen oxygenated metabolites of bupivacaine were detected, half of which were hydroxylated on nonaromatic groups. Equal numbers of mono- and dihydroxybupivacaines were excreted. There was no evidence to suggest the presence of (S)-4'-hydroxybupivacaine, 2'-hydroxymethylbupivacaine, 3'-hydroxy-2',6'-pipecoloxylidide or a piperidone. The metabolite previously identified as (S)-4'-hydroxybupivacaine was not hydroxylated on the xylyl group.


Current-Induced Helicity Reversal of a Single Skyrmionic Bubble Chain in a Nanostructured Frustrated Magnet.
Helicity indicates the in-plane magnetic-moment swirling direction of a skyrmionic configuration. The ability to reverse the helicity of a skyrmionic bubble via purely electrical means has been predicted in frustrated magnetic systems; however, it has been challenging to observe this experimentally. The current-driven helicity reversal of the skyrmionic bubble in a nanostructured frustrated Fe3 Sn2 magnet is experimentally demonstrated. The critical current density required to trigger the helicity reversal is 109 -1010 A m-2 , with a corresponding pulse-width varying from 1 µs to 100 ns. Computational simulations reveal that both the pinning effect and dipole-dipole interaction play a crucial role in the helicity reversal process.


Denture-reversing technique for assessing the soft tissue dimensional changes according to artificial tooth position in completely edentulous patients.
A digital workflow to assess the soft tissue dimensional changes in completely edentulous patients is described. Diagnostic casts obtained at 2 time points and the complete denture were scanned by using a desktop scanner. The denture scan was inverted by using a metrology software program to obtain the soft tissue contour. Using this reversed file as a reference, the file and 2 scan files obtained at different time points were aligned individually with the best fit alignment function. The scanned denture file and the 2 realigned scan files were imported into the same software. A plane vertical to the occlusal plane was determined such that it moved anteroposteriorly. The distance between the contours of the 2 realigned files was measured by selecting a point and a vector based on the artificial tooth positions of the denture. This technique of using a reversed denture file may provide a quantitative evaluation of soft tissue changes and further aid in determining appropriate intervals for denture relining or rebasing.


Subtle obstructive uropathy resulting from encasement of the ureters by tumor.
The diagnosis of obstructive uropathy may be difficult in the occasional case in which there is little or no dilatation of the collecting system. A case is presented in which anuric renal failure resulted from encasement of the ureters by tumor. The excretory urogram revealed a delayed pyelogram and a dense nephrogram with minimal dilatation of the collecting systems. The combination of a dense nephrogram and delayed pyelogram should raise the possibility of obstruction, regardless of the appearance of the collecting systems.


Immunomodulation via macrophages to fight solid tumor malignancies.
The paper 'A C-Terminal Fragment of Adhesion Protein Fibulin-7 Inhibits Growth of Murine Breast Tumor by Regulating Macrophage Reprogramming' by Chakraborty et al. highlights that Fbln7-C could be explored as a potential immunomodulatory agent against various solid cancers and have shown its abilities to regulate tumor microenvironment reprogramming of TAMs in a breast cancer model. Fbln7, which is a secreted glycoprotein, has been shown to be anti-angiogenic and has an immunomodulatory role regulating various functional properties of monocytes, macrophages, and neutrophils, thereby influencing inflammation. In this study, the authors have shown that in a murine breast tumor model, intravenous administration of Fbln7-C significantly reduces the size of tumors via macrophage reprogramming. Comment on: https://doi.org/10.1111/febs.15333.


[Biological aspects of the recurrence of malignant tumors].
Certain aspects of the differences between primary and recurrent tumours, such as the causes of the origin of recurrences, kinetic of the growth, characteristic of the recurrences as nonidentical population with primary tumour, immunological aspects, different changes in the tumour host have been reviewed. The prospects of the treatment of tumour recurrences have been discussed.


Comparing the accuracy of the da Vinci Xi and da Vinci Si for image guidance and automation.
Current laparoscopic surgical robots are teleoperated, which requires high fidelity differential motions but does not require absolute accuracy. Emerging applications, including image guidance and automation, require absolute accuracy. The absolute accuracy of the da Vinci Xi robot has not yet been characterized or compared to the Si system, which is now being phased out. This study compares the accuracy of the two. We measure robot tip positions and encoder values assessing accuracy with and without robot calibration. The Si is accurate if the setup joints are not moved but loses accuracy otherwise. The Xi is always accurate. The Xi can achieve submillimetric average error. Calibration improves accuracy, but excellent baseline accuracy of the Xi means that calibration may not be needed for some applications. Importantly, the external tracking systems needed to account for setup joint error in the Si are no longer required with the Xi.


Transcriptome responses of duodenal epithelial cells to prolactin in pituitary-grafted rats.
Chronic prolactin (PRL) exposure can affect several functions of duodenal epithelia, especially those associated with fluid and electrolyte transport. However, little is known regarding its molecular mechanism. To identify PRL-regulated genes, microarray analysis was performed on RNA samples from duodenal epithelial cells of anterior pituitary (AP)-grafted hyperprolactinemic rats. Herein, we identified 321 transcripts upregulated and 241 transcripts downregulated after 4 weeks of AP transplantation. Results from real-time PCR analyses of 15 selected genes were consistent with the microarray results. Gene ontology analysis demonstrated pleiotropic effects of PRL on several cellular processes, including cellular metabolic process, cell communication and cell adhesion. Interestingly, 17 upregulated transcripts and 12 downregulated transcripts are involved in the transport of ions and nutrients, e.g., Ca(2+), Na(+), K(+), Cl(-) and glucose, thus agreeing with the established action of PRL on electrolyte homeostasis. The present results provided fundamental information for further investigations on mechanism of PRL actions in the intestine.


Adjuvant trials of aromatase inhibitors: determining the future landscape of adjuvant endocrine therapy.
This review will discuss the role of aromatase inhibitors (AIs) in the adjuvant setting, and will summarize major strategies behind individual adjuvant trials using aromatase inhibitors. Studies with the third generation AIs including anastrozole, letrozole and exemestane, have shown better outcome and improved therapeutic ratio over second line hormonal approaches (i.e. progestins or aminoglutethimide) and, more recently, over tamoxifen also. These promising results have led recently to testing of AIs in the adjuvant setting for postmenopausal patients. Most trials now in progress are evaluating the role of new AIs versus tamoxifen (T) given x 5 years, which in most institutions is currently the standard hormonal adjuvant therapy for breast cancer. Three adjuvant approaches are being tested. First is the use of AI+T x 5 years in combination versus each agent alone, as reflected in the recently completed ATAC trial. Second is a sequential approach T first x 2-3 years followed by AIs x 2-3 years, or the other way round; and third, T x 5 years followed by AIs for additional 5 years (i.e. total duration of adjuvant hormones of 10 years). Many patients in the above trials will survive their first cancer. Hence, the non-oncological outcomes known to be affected by hormones are of rising importance. Therefore, the assessment of lipids as surrogates for cardiovascular morbidity, and of bone mineral status, as a marker for osteoporosis/bone fractures, is an important component of these trials. Also discussed in this review are proposals for future studies of AIs with focus on hormone resistance, such as early alteration of multiple hormonal agents or their intermittent use, the impact of the new generation of SERMs or 'pure' antiestrogens on activity of AIs, and the rising importance of AIs interacting with biologicals, cytokines or hormone modulators.


An approach to achieve long-term expression in skin gene therapy.
For gene therapy purposes, the skin is an attractive organ to target for systemic delivery of therapeutic proteins to treat systemic diseases, skin diseases, or skin cancer. To achieve long-term stable expression of a therapeutic gene in keratinocytes (KC), we have developed an approach using a bicistronic retroviral vector expressing the desired therapeutic gene linked to a selectable marker (multidrug resistant gene, MDR) that is then introduced into KC and fibroblasts (FB) to create genetically modified human skin equivalent (HSE). After grafting the HSE onto immunocompromised mice, topical colchicine treatment is used to select and enrich for genetically modified keratinocyte stem cells (KSC) that express MDR and are resistant to colchicine's antimitotic effects. Both the apparatus for topical colchicine delivery and the colchicine doses have been optimized for application to human skin. This approach can be validated by systemic delivery of therapeutic factors such as erythropoietin and the antihypertensive atrial natriuretic peptide.


Th17 and Treg cells function in SARS-CoV2 patients compared with healthy controls.
In the course of the coronavirus disease 2019 (COVID-19), raising and reducing the function of Th17 and Treg cells, respectively, elicit hyperinflammation and disease progression. The current study aimed to evaluate the responses of Th17 and Treg cells in COVID-19 patients compared with the control group. Forty COVID-19 intensive care unit (ICU) patients were compared with 40 healthy controls. The frequency of cells, gene expression of related factors, as well as the secretion levels of cytokines, were measured by flow cytometry, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay techniques, respectively. The findings revealed a significant increase in the number of Th17 cells, the expression levels of related factors (RAR-related orphan receptor gamma [RORγt], IL-17, and IL-23), and the secretion levels of IL-17 and IL-23 cytokines in COVID-19 patients compared with controls. In contrast, patients had a remarkable reduction in the frequency of Treg cells, the expression levels of correlated factors (Forkhead box protein P3 [FoxP3], transforming growth factor-β [TGF-β], and IL-10), and cytokine secretion levels (TGF-β and IL-10). The ratio of Th17/Treg cells, RORγt/FoxP3, and IL-17/IL-10 had a considerable enhancement in patients compared with the controls and also in dead patients compared with the improved cases. The findings showed that enhanced responses of Th17 cells and decreased responses of Treg cells in 2019-n-CoV patients compared with controls had a strong relationship with hyperinflammation, lung damage, and disease pathogenesis. Also, the high ratio of Th17/Treg cells and their associated factors in COVID-19-dead patients compared with improved cases indicates the critical role of inflammation in the mortality of patients.


Microbial Production of the Off-Flavor Geosmin in Tilapia Production in Brazilian Water Reservoirs: Importance of Bacteria in the Intestine and Other Fish-Associated Environments.
To determine major sources of microbially produced geosmin in the commercially important aquaculture fish species tilapia. Abundance and composition of geosmin-producing bacteria in water and fish biosphere (intestine, digesta, and fins) of Nile tilapia (Oreachromis niloticus) raised in net cages in Brazilian freshwater farms were examined. By combining qPCR of the geosmin synthase geoA gene and 16S rRNA gene amplicon sequencing to identify potential geosmin-producing organisms, we observed that the proportion and composition of geosmin producers appeared to be rather similar in the water, digesta, intestinal mucous, and on skin, making up about 0.1-0.2% of the total bacterial densities. A high proportion of Cyanobacteria and other putative geosmin producers affiliated to the Actinomycetales were identified in the intestinal mucous layer. The main uptake site for geosmin in fish is traditionally assumed to be through the gill surface, but the present results suggest that uptake by the intestinal tract may represent a major source of geosmin uptake in fish. The high abundance of geosmin-producing bacteria in the intestinal mucous layer and digesta may indicate that the digestive system in fish is an important, but hitherto overlooked, source of geosmin and likely other off-flavors in fish. Tainting of fish by microbially produced off-flavors spoils fish quality and lowers consumer preferences for aquaculture-produced freshwater fish. Our results highlight the potential for the application of probiotic microorganisms for management of the intestinal microflora to improve the fish quality. -Off-flavor producing bacteria are widely abundant in aquaculture.-Off-flavor producers found on skin surface of fish.-Off-flavor producing bacteria accumulate in the digestive system.-Off-flavor producers might release significant amounts of off-flavor during lysis in the gut.-Off-flavor uptake through the digestive system might be quantitatively significant.


The determination of glycyrrhizic acid in Glycyrrhiza uralensis Fisch. ex DC. (Zhi Gan Cao) root and the dried aqueous extract by LC-DAD.
A rapid, sensitive and specific reversed phase high-performance liquid chromatographic (LC) method with photodiode array detection (DAD) has been developed for the determination of glycyrrhizic acid in both the raw herb and a commercially prepared dried aqueous extract of Glycyrrhiza uralensis Fisch. ex DC. root (Zhi Gan Cao, liquorice). It was determined that extracting the raw herb in aqueous methanol (50:50 v/v) by sonication for 2 x 30 min was the most efficient sample preparation. Baseline resolution of the glycyrrhizic acid peak was achieved on a Varian Polaris RP C18-A (250 mm x 4.6 mm, 5 microm packing) column using an isocratic mobile phase consisting of 0. v aqueous phosphoric acid and acetonitrile in the ratio 60:40 v/v. Chromatograms were monitored between 200 and 400 nm for peak purity assessments, with quantitation performed at 254 nm. Glycyrrhizic acid calibration curves in the concentration range of 14-558 microg/ml were prepared on the day of analysis. Curve fitting was by the least-squares method, with correlation coefficients of >0.9998 obtained each time. The average recovery at three spike levels (50, 100, 200%) was of 95.91+/-1.05% and 98.36+/-3.45% (+/-S.D., n=7) for the spiked raw herb and dried aqueous extract respectively. The limit of detection and limit of quantitation was 0.52 and 1.72 mg/g respectively for the raw herb, and 0.75 and 2.51 mg/g respectively for the dried aqueous extract. Identity confirmation of the chromatographic peak was achieved by (-) electrospray ionisation tandem mass spectrometry. The concentration of glycyrrhizic acid in the root and dried aqueous extract was found to be 31.1+/-0.2 and 40.4+/-0.3mg/g (+/-S.D., n=7) respectively.


Comparison of taurine and pantoyltaurine as antioxidants in vitro and in the central nervous system of diabetic rats.
This study has comparatively evaluated the antiradical and antilipid peroxidizing actions of taurine (TAU) and its N-pantoyl analog pantoyltaurine (PTAU) in vitro, and has determined the extent to which these findings agree with the in vivo ability of these compounds to prevent changes in plasma glucose and in indices of oxidative stress in the plasma, brain and spinal cord induced by the diabetogen streptozotocin (STZ) in Sprague-Dawley rats. Using free radical-generating and oxidizing systems, PTAU was found more effective than TAU in scavenging DPPH, hydroxyl, peroxyl, and superoxide anion radicals and peroxynitrite, and in preventing lipid peroxidation of a brain homogenate by iron (III)-dopamine and the oxidation of dopamine by iron (III). On the other hand, when administered intraperitoneally (i.p.) at a 1.2mM/kg dose, 75min and 45min before a single i.p., 60mg/kg, dose of (STZ), TAU was about equipotent with PTAU in attenuating STZ-induced increases in glucose, malondialdehyde (MDA) and nitric oxide (NO), and the loss of reduced glutathione (GSH) in plasma collected at 24h post STZ. Moreover, the analysis of concurrently collected brain and spinal cords samples revealed that both TAU and PTAU were able to equally reverse the increases in MDA and NO concentrations and to effectively counteract the decrease in the GSH/GSSG ratio caused by STZ. Likewise, both compounds were very effective in preventing the losses of tissue catalase, glutathione peroxidase and superoxide dismutase activities. A comparison of the results for spinal cord and for brain parts such as the cerebellum, cortex and brain stem suggested the existence of regional differences in antioxidant potency between TAU and PTAU, especially in terms of antioxidant enzymes. In general, differences in antiradical and antioxidant potencies between TAU and PTAU derived from in vitro test are not reliable indicators of the antioxidant potencies these compounds may subsequently manifest in a living organism.


MRI demonstration of acute myocardial infarction due to posttraumatic coronary artery dissection.
A case of left ventricular lateral wall myocardial infarction in the distribution of circumflex coronary artery (LCX) was demonstrated by magnetic resonance imaging in a 55-year-old woman. Dissection of the proximal LCX due to blunt chest trauma was followed by percutaneous coronary artery stenting. MR (magnetic resonance) imaging of myocardial infarction is reviewed.


Metabolism by the rabbit of intravenously administered adenine.
A study was made of the metabolism by the rabbit of adenine administered intravenously at a dose of 35 mg/kg with 100 micronCi of 8-14C-adenine. The infused adenine was removed from the blood in two phases, first by diffusion into the tissues and second by metabolic reactions throughout the body. The adenine equilibrated within a few seconds equally between plasma and red blood cells and between them and kidney, liver, duodenum, lung and heart. Diffusion into skeletal muscle was much slower and into brain slowest. The more gradual disappearance of adenine from blood, and from the rest of the body, with a half-life of about 20 minutes and with complete removal by two hours, was predominantly along three pathways, leading to, after four hours: 1) 74 per cent in adenine nucleotide (mostly AMP, ADP, and (ATP); 2) 12 per cent as unchanged adenine in the urine; and 3) 11 per cent as a mixture in almost equal parts of 8-oxyadenine and 2,8-dioxyadenine in the urine. Conversion of adenine to adenine nucleotide, probably by initial reaction with phosphoribosyl pyrophosphate and adenine-phosphoribosyltransferase, was at widely different rates in the organs with duodenum, kidney, liver, and lung high and heart, red blood cell, skeletal muscle and brain relatively low. Sites of formation of the two oxyadenines, probably by action of xanthine oxidase, were not determined.


Capture of Triatoma arthurneivai (Hemiptera: Reduviidae) using a new luminous trap in Southeast Brazil.
Triatomine bug captures in the wild are laborious and time-consuming. Some traps may assist in this task. We report a new trap design and the capture of a specimen of a triatomine rarely found. Two luminous traps were installed in the city of Diamantina, State of Minas Gerais, and surveyed weekly for a year. A Triatoma arthurneivai female and other triatomine bugs were caught. A new trap design may be used in triatomine bugs field captures, mainly in low density areas. We assume the center of endemism of Triatoma arthurneivai is the Espinhaço Mountain range.


Pro-and anti-inflammatory effects of glucocorticoid Fluticasone on ovarian and immune functions in commercial-aged laying hens.
Ovarian chronic inflammation has been created and extended in the laying hen mainly via increasing laying frequency and microbial infection, especially during the late stage of production period. This study was aimed to evaluate glucocorticoid (GC) Fluticasone as an anti-inflammatory agent on the gene expression of the ovarian pro-and anti-inflammatory mediators (follicular cyclooxygenases COX 1, 2, and cytokines), inflammatory responses of the immune system, ovarian functions (ovulation rate and follicular growths), and hormones in the commercial-aged laying hens. White Leghorn hens aged 92-weeks were used for four weeks to be supplemented by 2 ppm Fluticasone as an optimum dose obtained in a pre-trial base on ovulation rate. As compared to control, Fluticasone resulted in a significant decrease in the mRNA expression of COX-1 and pro-and anti-inflammatory cytokines, and increase in COX-2 mRNA expression and heterophil to lymphocyte ratio (P < 0.001). A significant reduction was observed in the ovulation rate, follicular size (P < 0.001), ovarian hormones, immunoglobulins, body weight, and food consummation (P ≤ 0.05) by administering GC Fluticasone. Although a relative anti-inflammatory improvement was created by Fluticasone in the ovarian condition, the administration of this glucocorticoid resulted in a considerable reduction in ovarian hormones and functions of commercial aged laying hens.


Gas composition during thermochemical conversion of dry solid fuels and waste-derived slurries.
Coal has long remained a promising and widely used energy resource all over the world. Special emphasis is usually put on the research and development of environmentally friendly technologies for the use of coal and coal processing waste. The development of slurry fuels based on coal waste is one of the promising ways to use raw materials with energy potential, recover wastes, and reduce the environmental load. However, no combustion technology has yet been created for heterogeneous wastes as water-based slurries. The physical principles and parameters of the corresponding processes have not been studied adequately. In this research, the environmental combustion indicators (CO2, CO, H2, NOx, and SO2 concentrations) of slurries based on water and petrochemical, coal, and plant wastes were analyzed for the first time in a wide range of temperatures covering all the typical stages of thermochemical fuel conversion: pyrolysis (400-700 °C), gasification (700-900 °C), and combustion (700-1000 °C). We established the key patterns and aspects of changes in gas concentrations at all the main stages during the thermal decomposition of fuels. The use of water-based fuels at the pyrolysis stage was notable for up to 96% higher concentrations of the key combustible gases (CO, H2). The temperature extrema were 50-100 °C lower than those of bituminous coal. In terms of the key anthropogenic emissions (CO2, NOx, and SO2), the combustion of slurries also appeared to be 20-77% more environmentally friendly than that of coal depending on the temperature conditions and fuel composition. The maximum positive effect from adding biomass to coal-water slurries was achieved in the temperature range of 850 to 1000 °C. The research findings can be used for developing the technologies for thermal recovery of waste as water slurries, in particular, by intensifying the pyrolysis, gasification, and combustion.


Osteopontin overexpression in breast cancer: knowledge gained and possible implications for clinical management.
Osteopontin (OPN) is a secreted protein that is overexpressed in a number of human cancers, and has been associated with increased metastatic burden and poor prognosis in breast cancer patients. The OPN protein contains several conserved structural elements including heparin- and calcium-binding domains, a thrombin-cleavage site, a CD44 binding site, and two integrin-binding sites. Experimental studies have shown that the ability of OPN to interact with a diverse range of factors, including cell surface receptors (integrins, CD44), secreted proteases (matrix metalloproteinases, urokinase plasminogen activator), and growth factor/receptor pathways (TGFalpha/EGFR, HGF/Met) is central to its role in malignancy. These complex signaling interactions can result in changes in gene expression, which ultimately lead to alterations in cell properties involved in malignancy such as adhesion, migration, invasion, enhanced tumor cell survival, tumor angiogenesis, and metastasis. Therefore, OPN is not merely associated with cancer, but rather it plays a multi-faceted functional role via complex molecular cross-talk with other factors. This review will focus on the role of OPN in breast cancer, in particular on the malignancy-promoting aspects of OPN that may reveal opportunities for new approaches to the clinical management of breast cancer.


Underrepresented patient views and perceptions of personalized medication treatment through pharmacogenomics.
Within an institutional pharmacogenomics implementation program, we surveyed 463 outpatients completing preemptive pharmacogenomic testing whose genetic results were available to providers for guiding medication treatment. We compared views and experiences from self-reported White and Black patients, including education level as a covariate across analyses. Black patients were less confident about whether their providers made personalized treatment decisions, and overwhelmingly wanted a greater role for their genetic information in clinical care. Both groups similarly reported that providers asked their opinions regarding medication changes, but White patients were more likely (59% vs. 49%, P = 0.005) to discuss the impact of personal/genetic makeup on medication response with providers, and Black patients reported initiating such discussions much less frequently (4% vs. 15%, P = 0.037). Opportunities exist for enhanced communication with underrepresented patients around personalized care. Tailored communication strategies and development of support tools employed in diverse healthcare settings may facilitate pharmacogenomically guided medication treatment that equitably benefits minority patient populations.


Effects of nitroglycerin on the uterine and umbilical circulation in severe preeclampsia.
To determine the effects of nitroglycerin on placental circulation in severe preeclampsia. Twelve women with severe preeclampsia were examined. Uterine and umbilical artery pulsatility indices (PI) were assessed by pulsed Doppler ultrasound before and after infusion of nitroglycerin, starting at 0.25 micrograms/kg per minute with stepwise dosage increases until a diastolic blood pressure (BP) of 100 mmHg was achieved. Blood pressure and heart rate were recorded every 5 minutes. Blood was sampled for analysis of the second messenger of nitric oxide, cyclic guanosine monophosphate (cGMP), before and at the end of the infusion. During the infusion, the mean systolic BP decreased from 161 (95% confidence interval [CI] 154-169) to 138 mmHg (95% CI 131-146), and the diastolic pressure decreased from 116 (95% CI 111-122) to 103 (95% CI 96-110) mmHg (P < .01). The PI of the uterine artery did not change significantly (1.23 [95% CI 1.01-1.61]) versus 1.30 [95% CI 1.01-1.88]), whereas umbilical artery PI decreased significantly (P < .01), from 1.35 (95% CI 1.09-1.73) to 1.20 (95% CI 1.05-1.40), with a more pronounced decrease in patients with high basal values. Cyclic GMP remained essentially unchanged (6.4 [95% CI 5.4-7.7] versus 5.5 [4.7-6.6] nmol/L). The reduction in the PI of the umbilical artery during nitroglycerin-induced BP reduction implies vasodilation in the umbilical circulation. The absence of an increase in cGMP does not support the view that the nitroglycerin effect is reflected by the plasma concentration of cGMP.


Studies on steroids. CXXVIII. Separation and determination of bile acids by high-performance liquid chromatography.
A method is described for the simultaneous determination of major bile acids by high-performance liquid chromatography without prior hydrolysis. A mixture of bile acids is divided into the free, glyco- and tauro-conjugate groups by thin-layer chromatography. Separation of each group into cholate, ursodeoxycholate, chenodeoxycholate, deoxycholate and lithocholate is attained in two stages on a muBondapak C18 column; first, 0.3% ammonium carbonate-acetonitrile (9:4) is used as a mobile phase for the separation of the last three compounds. Subsequently cholate and ursodeoxycholate are resolved by chromatography in 0.3% ammonium carbonate-acetonitrile (11:4).


Colorimetric-detected DNA sequencing.
A sensitive, colorimetric method for visualizing the band pattern of DNA sequencing reaction is described. The enzymatic incorporation of radioactive nucleotides commonly used for the band detection is replaced by biotin conjugated to the 5'-terminus of a synthetic oligonucleotide by chemical synthesis. The oligonucleotide so labeled is used as a primer for dideoxy DNA sequencing in a primer extension reaction. The products of the sequencing reactions are analyzed on a denaturing polyacrylamide gel using the direct blotting electrophoresis technique. This technique makes it possible to transfer the band pattern during the electrophoresis onto an immobilizing matrix, on which it is made visible by an enzymatic reaction in less than 3 h. This biotin-based detection method is so sensitive that the sequencing reactions can be performed under the same conditions and concentrations as those for the radioactive detection.


Cream and sugar: human preferences for high-fat foods.
Sixteen normal-weight subjects rated the perceived intensity of sweetness, fatness, and creaminess of 20 different mixtures of milk, cream, and sugar, and assigned an overall pleasantness (hedonic) rating to each sample. Intensity estimates increased as power functions of ingredient concentration and no significant mixture suppression effect was observed. In contrast, hedonic responses strongly depended on the relative proportions of sucrose and fat in the samples tasted. Hedonic preference ratings first rose and then declined with increasing sucrose concentration, but continued to rise with increasing dairy fat content. The addition of sucrose greatly enhanced hedonic ratings for high-fat stimuli. Changes in hedonic responsiveness were monitored using a mathematical modelling technique known as the Response Surface Method, which allows computerized simulation of the hedonic response surface as a function of perceived ingredient levels. Overnight fasting did not affect the perception or hedonics for sweet or "fatty" tastes. The observed preference for sweetened high-fat foods may have implications for the development of dietary-induced obesity in man.


Modified technique for preservation of inferior alveolar nerve during mandibulectomy.
The purpose of this article is to introduce the modified technique of preservation of the inferior alveolar nerve (IAN) during mandibulectomy for a benign lesion. Five cases of osteofibrous hyperplasia and 3 cases of centricity osteomyelitis were included. During surgery, the IAN was marked using a planned cutting guide. Using an oscillating saw, the depth of the osteotomy along the IAN was controlled until the bone cortex was cut through. After splitting, the bony section was removed, leaving the neurovascular bundle intact. The sensation of the lower lip was evaluated using current perceptive threshold testing during follow-up. After follow-up for 6-27 months, no recurrence or secondary deformity was found. One patient had severe sensory disturbance. With the use of a cutting guide and osteotomy tricks, mandibulectomy with preservation of the IAN can be accurately performed.


[Screening for symptoms of depression during postpartum and the long term follow up: temporal stability and associated factors].
To describe the frequency of depressive symptoms compatible with a postpartum depression diagnosis, the associated factors and the temporal stability. During 2006-2007 398 hospitalized puerperal women who attended CEMIC were interviewed 5 days after childbirth using the Edinburgh Postnatal Depression Scale and a socio-demographic questionnaire. A logistic regression analysis was performed to identify associated factors with a positive screening. During the following 6-12 months a follow up was carried with two groups of similar characteristics. The frequency of depressive symptoms at post partum was 17.8% (cut off = 10). Depressive history and neonatal intensive care were significantly related to a positive screening. From the 110 interviewed women, 24 were positive in the follow-up. The prevalence of risk for postpartum depression in the sample of patients surveyed is within the parameters reported in international literature. At the 6 month follow up, 6 previously asymptomatic women during the first screening turned on positive. It is theorize the existence of potential postpartum depression cases that can manifest up to a year after childbirth.


The Hourglass Model: Are There Structural Problems with the Scarcity of Positive Results for Flexible ACT?
The aim of the present article was to discuss the commentary by van Veldhuizen, Delespaul and Mulder (2015) regarding the review by Nordén and Norlander (2014) based on five empirical articles about Flexible Assertive Community Treatment (FACT). Veldhuizen et al. agree on that there is insufficient evidence for the effectiveness of FACT. However, van Veldhuizen et al. avoid a discussion of the lack of positive results despite extensive research during several years and therefore an analysis of why FACT did not fare better is missing. According to FACT it is an advantage that one single team spans the entire chain of care and rehabilitation, but no evidence is given for such an opinion. Instead there may be difficulties for the staff to shift between psychiatric care and psychiatric rehabilitation and the clients perhaps don't want to encounter the same professional team during all phases of care and rehabilitation.


In vitro maturation: a committee opinion.
The results of in vitro maturation (IVM) investigations suggest the potential for wider clinical application. This document discusses the efficacy of IVM as reported in the published literature to date. This document replaces the document of the same name, last published in 2013.


Microarray analysis of gene expression involved in anther development in rice (Oryza sativa L.).
In flowering plants, anthers bear male gametophytes whose development is regulated by the elaborate coordination of many genes. In addition, both gibberellic acid (GA3) and jasmonic acid (JA) play important roles in anther development and pollen fertility. To facilitate the analysis of anther development genes and how GA3 and JA regulate anther development, we performed microarray experiments using a 10-K cDNA microarray with probes derived from seedlings, meiotic anthers, mature anthers and GA3- or JA-treated suspension cells of rice. The expression level change of 2155 genes was significantly (by 2-fold or greater) detected in anthers compared with seedlings. Forty-seven genes, representing genes with potential function in cell cycle and cell structure regulation, hormone response, photosynthesis, stress resistance and metabolism, were differentially expressed in meiotic and mature anthers. Moreover, 314 genes responded to either GA3 or JA treatment, and 24 GA3- and 82 JA-responsive genes showed significant changes in expression between meiosis and the mature anther stages. RT-PCR demonstrated that gene y656d05 was not only highly expressed in meiotic anthers but also induced by GA3. Strong RNA signals of y656d05 were detected in pollen mother cells and tapetum in in situ hybridization. Further characterization of these candidate genes can contribute to the understanding of the molecular mechanism of anther development and the involvement of JA and GA3 signals in the control of anther development in rice.


T lymphocytes that infiltrate nasal polyps have a specialized phenotype and produce a mixed TH1/TH2 pattern of cytokines.
Nasal polyps (NPs) are inflammatory reactions in the nasal mucosa the etiology and pathogenesis of which remains unknown. The purpose of this study was to study in detail the phenotype and function of T lymphocytes infiltrating NPs by analyzing the expression of surface markers and cytokine secretion. NP tissue samples and peripheral blood were obtained from 18 patients. Mononuclear cells were purified from these samples, and their phenotype was investigated by triple-color immunofluorescence and flow cytometric analysis. Cytokine production was determined in cultures by using an ELISA technique. NP lymphoid cells mainly consisted of T lymphocytes. These T lymphocytes showed a CD45RO+CD45RA- phenotype and expressed pan-T cell molecules; the CD8+ subset was predominant. NP T cells showed a lower density of CD28, CD3, and TCR-alphabeta compared with T cells from peripheral blood. NP T lymphocytes expressed the activation markers DR and CD69 and exhibited the adhesion molecule profile CD54+, CD62L-, and CD103+ CD49dlow. Virtually all NP T cells bore CD95 (FAS), but they did not undergo apoptosis, either spontaneously or induced by CD95 cross-linking with the mAb CH11. The pattern of cytokines secreted by NP T lymphocytes was characterized by the spontaneous and simultaneous production of IFN-gamma and IL-5. Neither IL-2 nor IL-4 were detectable in nonstimulated cultures. This study defines the T lymphocytes that infiltrate NPs as memory T cells in an activated status, with homing properties related to the mucosal immune system. They are resistant to anti-CD95-mediated apoptosis and produced a mixed TH1 /TH2 cytokine pattern as defined by the simultaneous production of IFN-gamma and IL-5.


Automated capillary electrophoresis with on-line preconcentration by solid phase extraction using a sequential injection manifold and contactless conductivity detection.
An extension of a capillary electrophoresis instrument coupled to a sequential injection analysis manifold was developed for automated measurements with on-line solid-phase extraction preconcentration. An in-house built capacitively coupled contactless conductivity detector was employed for sensitive detection with narrow capillaries of 25 μm internal diameter. The system was assembled into standardized 19 in. frames and racks for easy transport and mobile deployment. The system can be left running unattendedly without manual intervention with good operation stability. To demonstrate the application of the system, a method for the determination of four drugs, namely ibuprofen, diclofenac, naproxen and bezafibrate, was developed with enrichment factors of up to several hundreds. Detection of the drug residues down to the nM-scale was found possible and the method was found suitable for the detection of ibuprofen in the waste water of a hospital in Hanoi.


Phorbol ester-induced G1 phase arrest selectively mediated by protein kinase Cdelta-dependent induction of p21.
Although protein kinase C (PKC) has been widely implicated in the positive and negative control of proliferation, the underlying cell cycle mechanisms regulated by individual PKC isozymes are only partially understood. In this report, we show that PKCdelta mediates phorbol ester-induced G1 arrest in lung adenocarcinoma cells and establish an essential role for this novel PKC in controlling the expression of the cell cycle inhibitor p21. Activation of PKC with phorbol 12-myristate 13-acetate (PMA) in early G1 phase impaired progression of lung adenocarcinoma cells into S phase, an effect that was completely abolished by specific depletion of PKCdelta, but not PKCalpha. Although the PKC effect was unrelated to the inhibition of cyclin D1 expression, PKC activation significantly up-regulated p21 and down-regulated Rb hyperphosphorylation and cyclin A expression. Elevations in p21 mRNA and protein by PMA were mediated by PKCdelta but not PKCalpha. Studies using luciferase reporters also revealed an essential role for PKCdelta in the PMA-induced inhibition of Rb-dependent cyclin A promoter activity. Finally, we showed that the cell cycle inhibitory effect of PKCdelta is greatly attenuated by RNA interference-mediated knock-down of p21. Our results identify a novel link between PKCdelta and G1 arrest via p21 up-regulation and highlight the complexities in the downstream effectors of PKC isozymes in the context of cell cycle progression and proliferation.


Suspected microplastics in Atlantic horse mackerel fish (Trachurus trachurus) captured in Portugal.
Microplastics have been found in fish, but most studies have focused on the digestive system without considering additional organs. Herein, the objective was to assess the presence of microplastics in internal organs (gills, guts, kidney, heart) of the Atlantic horse mackerel (Trachurus trachurus) captured of the coast of Portugal (Northeast Atlantic Ocean). Suspected microplastics were present in all organs, with particles of larger size (i.e., equivalent diameter) found in the gut and those of lower size in the heart and its luminal blood. Suspected microplastics of 1-10 μm were the most abundant (65.4%), more likely to translocate, owing to their minute size, but more difficult to properly characterize. These results highlight the need to expand the analytical work on organs and tissues for assessing microplastics in organisms, but also emphasize the actual need for developing analytical methods that allow for an accurate isolation, identification, and characterization of microplastics in biota.


Learning surgical communication, leadership and teamwork through simulation.
In Australia and New Zealand, surgical trainees are expected to develop competencies across 9 domains. Although structured training is provided in several domains, there is little or no formal program for professionalism, communication, collaboration, and management and leadership. The Australian federal Department of Health and Aging funded a pilot course in simulation-based education to address these competencies for surgical trainees. This article describes the course and evaluation. Course development: Content and methods drew on best-evidence for teaching and learning these competencies from other disciplines. Course evaluation: Participants completed surveys using rating scales and free text comments to identify aspects of the course that worked well and those that needed improvement. Eleven of 12 participants completed evaluation forms immediately after the course. Participants reported largely meeting learning objectives and valuing the educational methods. High levels of realism in simulations contributed to the ease with which participants immersed themselves in scenarios. This study demonstrates that a course designed to teach competencies in communication, teamwork, leadership, and the encompassing professionalism to surgical trainees is feasible. Although participants valued the content and methods, they identified areas for development. Limitations of the evaluation are highlighted, and further areas for research are identified.


Sensitivity of murine B- and T-lymphocytes to oxazaphosphorine and non-oxazaphosphorine nitrogen mustards.
The relative sensitivities of murine B- and T-lymphocytes to the oxazaphosphorine nitrogen mustards, cyclophosphamide and ASTA Z 7557, and to the non-oxazaphosphorine nitrogen mustards, melphalan and chlorambucil, in vivo, were determined. B- and T-lymphocytes were defined by selective mitogen-induced proliferation. Lipopolysaccharide (LPS)-induced B-lymphocytes were approximately twice as sensitive to the cytotoxic effects of cyclophosphamide and ASTA Z 7557 as were phytohemagglutinin (PHA)- and concanavalin A (Con A)-induced T-lymphocytes. LPS-induced B-lymphocytes and PHA-induced T-lymphocytes were approximately equisensitive to the cytotoxic action of melphalan and chlorambucil, but the former were somewhat more sensitive to these agents than were Con A-induced T-lymphocytes. The relative sensitivities of murine B- and T-lymphocytes to ASTA Z 7557 and the non-oxazaphosphorine metabolite of cyclophosphamide, phosphoramide mustard, ex vivo, were also determined. LPS-induced B-lymphocytes were approximately twice as sensitive to the cytotoxic action of ASTA Z 7557 as were PHA- and Con A-induced T-lymphocytes. The three mitogen-induced lymphocyte populations were approximately equisensitive to the cytotoxic action of phosphoramide mustard. These observations suggest that the differential effect of cyclophosphamide on murine B- and T-lymphocytes is uniquely exhibited by oxazaphosphorine nitrogen mustards. Furthermore, the results suggest that 4-hydroxycyclophosphamide is the cyclophosphamide metabolite that mediates the differential immunotoxic effect of the parent compound.


Protective role of N-trans-feruloyltyramine against β-amyloid peptide-induced neurotoxicity in rat cultured cortical neurons.
Enhanced oxidative stress and inflammation play important roles in the pathogenesis of Alzheimer's disease (AD). Amyloid β-peptide (Aβ), a major component of amyloid plaques, is considered to have a causal role in the development and progress of AD by being the initiator of a pathological cascade leading to oxidative stress. The present study investigated the effect of N-trans-feruloyltyramine (NTF) purified from Polyalthia suberosa, an alkaloid shown to protect against oxidative stress and cell death. Pre-treatment of rat primary cortical cell cultures with 25-250μM NTF significantly attenuated 10μM Aβ(1-42)-induced neuronal death in a dose-dependent manner. Apoptotic cell death was demonstrated morphologically as well as by detection of the presence of activated caspase-3 and Bax, levels of which could be reduced by NTF pre-treatment. NTF also reduced production of reactive oxygen species induced by Aβ(1-42). These findings suggest that the protective effect of NTF against Aβ(1-42)-induced neuronal death might be due to its antioxidative property.


Evaluation of calix-crown ionophores for selective separation of radio-cesium from acidic nuclear waste solution.
Extraction of Cs-137 from nitric acid was carried out using nitrobenzene solutions of calix-crowns such as calix[4]arene-bis(crown-6) (CC-A), calix[4]arene-bis(benzo crown-6) (CC-B) and calix[4]arene-bis(napthocrown-6) (CC-C). CC-C was found to be superior extractant for Cs(I) as compared to the other two calix-crown ligands used in the present study. The effect of diluent on the extraction of Cs(I) indicated the trend: nitrobenzene>dichloroethane>chloroform>decanol>>carbon tetrachloride approximately n-hexane approximately toluene. Subsequently, the studies were carried out with nitrobenzene solutions of the calix-crown ligands (mainly CC-C) on the effects of (a) aqueous phase acidity, (b) ligand concentration, and (c) cesium concentration on Cs extraction from nitric acid media. Conditions for quantitative extraction and stripping were optimized and the extracted species conformed to {[CsL]+.[NO3]-.nH2O}. Selectivity studies were carried out using an irradiated natural U target involving tracer amount of fission products activities. Extraction of Cs(I) from a synthetic high level waste solution was also carried out. The promising results obtained in the present studies indicate possible use of the calix-crown ligand for Cs(I) recovery from the acidic high level waste.


Partial substitution of manure reduces nitrous oxide emission with maintained yield in a winter wheat crop.
Conventional fertilization of agricultural soils results in increased N2O emissions. As an alternative, the partial substitution of organic fertilizer may help to regulate N2O emissions. However, studies assessing the effects of partial substitution of organic fertilizer on both N2O emissions and yield stability are currently limited. We conducted a field experiment from 2017 to 2021 with six fertilizer regimes to examine the effects of partial substitution of manure on N2O emissions and yield stability. The tested fertilizer regimes, were CK (no fertilizer), CF (chemical fertilizer alone, N 300 kg ha-1, P2O5 150 kg ha-1, K2O 90 kg ha-1), CF + M (chemical fertilizer + organic manure), CFR (chemical fertilizer reduction, N 225 kg ha-1, P2O5 135 kg ha-1, K2O 75 kg ha-1), CFR + M (chemical fertilizer reduction + organic manure), and organic manure alone (M). Our results indicate that soil N2O emissions are primarily regulated by soil mineral N content in arid and semi-arid regions. Compared with CF, N2O emissions in the CF + M, CFR, CFR + M, and M treatments decreased by 16.8%, 23.9%, 42.0%, and 39.4%, respectively. The highest winter wheat yields were observed in CF, followed by CF + M, CFR, and CFR + M. However, the CFR + M treatment exhibited lower N2O emissions while maintaining high yield, compared with CF. Four consecutive years of yield data from 2017 to 2021 illustrated that a single application of organic fertilizer resulted in poor yield stability and that partial substitution of organic fertilizer resulted in the greatest yield stability. Overall, partial substitution of manure reduced N2O emissions while maintaining yield stability compared with the synthetic fertilizer treatment during the wheat growing season. Therefore, partial substitution of manure can be recommended as an optimal N fertilization regime for alleviating N2O emissions and contributing to food security in arid and semi-arid regions.


MRI study of the pituitary gland in adolescent depression.
Abnormalities in pituitary function have been described in major depressive disorder (MDD) and may reflect neurodevelopmental abnormalities. We hypothesized alterations in the pituitary in early onset MDD. We measured the volume of the pituitary gland in 17 MDD (mean+/-S.D.=16.67+/-1.83 years; 8M, 9F) patients and 17 age and sex matched healthy controls (mean+/-S.D.=16.23+/-1.61 years; 8M, 9F) using 1.45 mm thick T(1)-weighted coronal MRI images. A trained rater blind to diagnosis did all measurements. ANCOVA covarying for age, sex and intracranial volume (ICV) revealed a significant difference between the two groups (F=6.43, df=1, 29, P=0.02; MDD subjects demonstrated a 25% increase in pituitary gland volume). Age was significantly correlated with pituitary volume in the healthy controls (r=0.62, P=0.008) but not the MDD group. No significant relationships between pituitary size and clinical severity were found in the MDD patients. To our knowledge, this is the first study that reports larger pituitary volumes in early onset major depression. These findings provide new evidence of abnormalities of the pituitary in early onset MDD, possibly related to neuroendocrine dysfunction.


Acquired cystic kidney disease in renal insufficiency: a multicentre study. Group of Nephrologists of the East of France.
A cross-sectional study was undertaken in order to a) investigate the prevalence of acquired cystic kidney disease and the prevalence of associated cancer; b) evaluate the best diagnostic procedure; c) look for a possible relationship with improvement of anaemia. All patients treated in 10 Dialysis Centres in the East of France, except those with polycystic kidney disease, were examined during the same 6-month period by echography and computed tomography scanning, when they were at initiation of dialysis (T0) or when they reached exactly 5 years (T5), 10 years (T10), 15 years or more (T15) of dialysis. One hundred sixty-one patients were evaluated: 50 at T0, 48 at T5, 33 at T10 and 30 at T15. a) Prevalence of acquired cystic kidney disease was 57.2%, ranging from 30% at T0 to 83.3% at T15; prevalence of associated cancer was 1.1%; b) computed tomography was the best diagnostic procedure, but when compared with it, echography had a sensibility of 0.88 and a specificity of 1; c) only in patients with large-sized cystic kidneys, there was an improvement of anaemia.


Immune and metabolic responses of Chilo suppressalis Walker (Lepidoptera: Crambidae) larvae to an insect growth regulator, hexaflumuron.
Efficient control of Chilo suppressalis Walker is always controversial due to highly economic damage, resistance to insecticides and environmental pollutions. So, combination of safe pest controls e.g. biocontrol agents and insect growth regulators seems to be promising via integrated pest management program. Bioassay of hexaflumuron on 4th larval instars revealed concentrations of 44.34, 179.74 and 474.94µg/ml as LC10-50 values. Numbers of total hemocytes, plasmatocytes and granulocytes as well as phenoloxidase activity increased in the different time intervals following treatment by hexaflumuron. Combined effects of hexaflumuron and Beauveria bassiana Vuillemin also increased hemocyte numbers and phenoloxidase activity at different time intervals using all concentrations. Activities of general esterases assayed by α- and β-naphtyl acetate and glutathione S-transferase using CDNB and DCNB increased 1-12h post-treatment. Activities of aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase and aldolase increased in the larvae treated by hexaflumuron. However enhanced activity of lactate dehydrogenase was only obtained by treating 180 and 470µg/ml concentrations of hexaflumuron. Activities of ACP and ALP were found to be higher than control for all time intervals even 1-12h post-treatment. The amounts of HDL and LDL increased in the highest concentrations of hexaflumuron after 12-24h of post-treatment. Amount of triglyceride was higher than that of control after 1 and 3h but it was lower in other time intervals. Amounts of glycogen and protein were lower than those of control for all time intervals except for 6 and 12h of post-treatment in case of protein. Results of the current study revealed negative effects of hexaflumuron on intermediary metabolism of Chilo suppressalis but it increased the number of hemocytes and activity of phenoloxidase which are responsible for spore removal from hemolymph. It can be concluded that hexaflumuron is able to decrease survival and biological performance of C. suppressalis via intervening in intermediary metabolism but the given results showed incompatibility of the IGR with possible microbial control.


Cervical carcinoma induces NLRP3 inflammasome activation and IL-1ß release in human peripheral blood monocytes affecting patients' overall survival.
Our group previously demonstrated that genetic variants in inflammasome genes contribute to protection against the establishment of human papilloma virus (HPV)-associated cervical carcinoma (CC). The objective of this study was to better understand the contribution of inflammasome and its cytokines in the CC microenvironment. The inflammasome activation was analyzed in CC tumoral cell lines and healthy donors (HD)' monocytes in co-culture. In vitro results were then compared to CC patients' public databases. CC cells did not produce IL-1ß or IL-18 themselves, however, when in co-culture with HD monocytes, induced IL-1ß release in those leucocytes. Inflammasome activation appears to be partially dependent on the NLRP3 receptor. Public data analysis revealed that IL1B expression is increased in the CC compared to normal uterine cervix, and that patients with high IL1B expression had a shorter overall survival. CC microenvironment can activate the inflammasome and IL-1ß release in surrounding monocytes, which could be detrimental for CC prognosis.


Moving to greener pastures: Health selection into neighborhood green space among a highly mobile and diverse population in California.
Global urbanization has sparked substantial environmental, public health, and social science research on the importance of conserving and propagating natural environments. A large subset of this work focuses on the benefits of green space for health. An often-overlooked methodological concern when examining relations between green space and health, however, involves residential self-selection. The selective movement of individuals into greener neighborhoods on the basis of preexisting health and correlated social factors may bias associations, particularly in cross-sectional studies, which predominate existing green space/health research. To quantify the extent of residential self-selection bias, this study used a longitudinal sibling comparison design with repeated individual and neighborhood measures to estimate associations between pre-move health factors, including maternal body mass index (BMI) and infant birthweight, and post-move neighborhood green space in a residentially mobile sample of mothers in California, 2007 to 2015 (n = 288,333). Results show that better health before moving predicted higher levels of neighborhood green space after moving, providing evidence of health selection. Findings also indicate some support for differential health selection into neighborhood green space by race/ethnicity, including that evidence of selection emerges for white and Hispanic, but not Black, mothers. However, weak relations between pre-move individual factors and post-move neighborhood green space across analyses suggest that potential bias due to residential self-selection appears relatively minimal in a large, diverse, and highly mobile sample of families in California. Findings support calls to increase green space in historically marginalized neighborhoods as a means to promote environmental and health equity.


Primary pleomorphic liposarcoma of the larynx.
Liposarcoma is a rare tumor in the larynx. A case of such lesion occurring in a 52 year old male patient is described. This is the second case to be reported in the world literature. The patient underwent hemilaryngectomy and later total laryngectomy for a recurrent tumor and is living and well six years after diagnosis.


Congenital microcephaly, infantile spasms, psychomotor retardation, and nephrotic syndrome in two sibs.
Two boys are described with congenital microcephaly, infantile spasms, psychomotor retardation and an early-onset nephrotic syndrome. The autopsy findings of one patient are described in detail. Polymicrogyria was the most prominent feature and the kidneys showed focal segmental glomerulosclerosis. These findings have been described as a clinical entity, the leading symptoms being congenital microcephaly, early-onset nephrotic syndrome and mental retardation, accompanied by various other clinical symptoms. A review of the literature suggests an autosomal recessive mode of inheritance.


A Pilot Open Trial of a Digital Mindfulness-Based Intervention for Anorexia Nervosa.
Anorexia nervosa (AN) is a chronic and debilitating psychiatric disorder. Unfortunately, current treatments are lacking, with only 30-50% of individuals with AN recovering after treatment. We developed a beta-version of a digital mindfulness-based intervention for AN called Mindful Courage-Beta, which includes: (a) one foundational multimedia module; (b) 10 daily meditation mini-modules; (c) emphasis on a core skill set called the BOAT (Breathe, Observe, Accept, Take a Moment); and (d) brief phone coaching for both technical and motivational support. In this open trial, we aimed to evaluate (1) acceptability and feasibility; (2) intervention skill use and its association with state mindfulness in daily life; and (3) pre-to-post changes in target mechanisms and outcomes. Eighteen individuals with past-year AN or past-year atypical AN completed Mindful Courage-Beta over 2 weeks. Participants completed measures of acceptability, trait mindfulness, emotion regulation, eating disorder symptoms, and body dissatisfaction. Participants also completed ecological momentary assessment of skill use and state mindfulness. Acceptability ratings were good (ease-of-use: 8.2/10, helpfulness: 7.6/10). Adherence was excellent (100% completion for foundational module and 96% for mini-modules). Use of the BOAT in daily life was high (1.8 times/day) and was significantly associated with higher state mindfulness at the within-person level. We also found significant, large improvements in the target mechanisms of trait mindfulness (d = .96) and emotion regulation (d = .76), as well as significant, small-medium to medium-large reductions in eating disorder symptoms (ds = .36-.67) and body dissatisfaction (d = .60). Changes in trait mindfulness and emotion regulation had medium-large size correlations with changes in global ED symptoms and body dissatisfaction (rs = .43 - .56). Mindful Courage-Beta appears to be promising and further research on a longer, refined version is warranted.


Nurses' perceptions of their supportive role for cancer patients: A qualitative study.
Supporting cancer patients is one of the integral, ethical and professional components and concepts of nursing care. Given the prominence of nurses' understanding of their supportive role in providing quality and humane nursing care for cancer patients, it is crucial for them to acquire sufficient knowledge to achieve a positive attitude towards patient support. Qualitative conventional content analysis approach was used. This study was conducted with a qualitative approach and conventional content analysis in 2020. Participants consisted of 18 nurses of different oncology wards of teaching hospitals in Northwestern Iran recruited using the purposive sampling method. Data were collected through semi-structured interviews and analysed simultaneously with data collection (22 july - 20 june 2020). The analysis of interviews showed that the main theme of "a canopy as a supportive role for cancer patients" was formed. In this theme, related subcategories included patient's psychological support (compassionate care with emotional support, having an intimate/friendly relationship with the patient and communicative behaviour facing patient needs), patient training (need-based training, having good theoretical knowledge about the patient and having a role model for playing a supportive role for the patient) and supporting the patient with clinical self-efficacy (being responsible with clinical competency, understanding the patient's behaviour and attempt to provide extra-duty care).


Molecular Identification of Leishmania spp. in Sand Flies (Diptera: Psychodidae, Phlebotominae) From Ecuador.
The detection and identification of natural infections in sand flies by Leishmania protozoan species in endemic areas is a key factor in assessing the risk of leishmaniasis and in designing prevention and control measures for this infectious disease. In this study, we analyzed the Leishmania DNA using nuclear ribosomal internal transcript spacer (ITS) sequences. Parasite DNA was extracted from naturally infected, blood-fed sand flies collected in nine localities considered leishmaniasis-endemic foci in Ecuador.The species of parasites identified in sand flies were Leishmania major-like, Leishmania naiffi, Leishmania mexicana, Leishmania lainsoni, and "Leishmania sp. siamensis". Sand fly specimens of Brumptomyia leopoldoi, Mycropigomyia cayennensis, Nyssomyia yuilli yuilli, Nyssomyia trapidoi, Pressatia triacantha, Pressatia dysponeta, Psychodopygus carrerai carrerai, Psychodopygus panamensis, and Trichophoromyia ubiquitalis were found positive for Leishmania parasite. These findings contribute to a better understanding of the epidemiology and transmission dynamics of the disease in high-risk areas of Ecuador.


Improving de novo protein binder design with deep learning.
Recently it has become possible to de novo design high affinity protein binding proteins from target structural information alone. There is, however, considerable room for improvement as the overall design success rate is low. Here, we explore the augmentation of energy-based protein binder design using deep learning. We find that using AlphaFold2 or RoseTTAFold to assess the probability that a designed sequence adopts the designed monomer structure, and the probability that this structure binds the target as designed, increases design success rates nearly 10-fold. We find further that sequence design using ProteinMPNN rather than Rosetta considerably increases computational efficiency.


You're the Flight Surgeon: Renal Cell Carcinoma.
Searson-Norris L. You're the flight surgeon: renal cell carcinoma. Aerosp Med Hum Perform. 2019; 90(12):1064-1068.


Recurrence and visual prognostic factors of polypoidal choroidal vasculopathy: 5-year results.
This retrospective study aimed to evaluate the factors affecting recurrence and visual prognosis in patients with treatment-naïve subfoveal polypoidal choroidal vasculopathy (PCV). Patients who had received three consecutive intravitreal injections of ranibizumab or aflibercept and had reached remission were enrolled. They were divided into a group without recurrence (group 1, 26 eyes) and a group with recurrence (group 2, 121 eyes) and followed up for at least 5 years. Patients in group 2 received additional treatment for worsening. Logistic regression analysis revealed that a young age of onset (P = 0.001), high choroidal vascularity index (CVI; P = 0.019), and presence of choroidal vascular hyperpermeability (CVH; P = 0.037) were associated with a low risk of recurrence. Multiple regression analysis revealed that recurrence (P = 0.001), greatest linear dimension (P = 0.003), and polyp configuration (single or cluster; P = 0.043) were associated with final visual acuity. Patients without recurrence had a lower age of onset and higher CVI than those with recurrence, and they tended to have CVH. In addition, patients with recurrence, large lesion, and cluster polyps had worse final visual acuity than those without these factors. CVI and CVH may be used to predict recurrence of PCV.


Birth cohort differences in cognitive performance in 75- and 80-year-olds: a comparison of two cohorts over 28 years.
To evaluate cohort differences in cognitive performance in older men and women born and assessed 28 years apart. Data in this study were drawn from two age-homogeneous cohorts measured in the same laboratory using the same standardized cognitive performance tests. Participants in the first cohort were born in 1910 and 1914 and assessed in 1989-1990 (Evergreen project, n = 500). Participants in the second cohort were born in 1938 or 1939 and 1942 or 1943 and assessed in 2017-2018 (Evergreen II, n = 726). Participants in both cohorts were assessed at age 75 and 80 years and were recruited from the population register. Cognitive performance was measured using the Digit Span test from the Wechsler Memory Scale (WMS), Digit Symbol test from the Wechsler Adult Intelligence Scale (WAIS) and phonemic Verbal Fluency test from the Schaie-Thurstone Adult Mental Abilities Test. Reaction time assessing motor and mental responses was measured with a simple finger movement task, followed by a complex finger movement task. T-tests were used to study cohort differences and linear regression models to study possible factors underlying differences. We found statistically significant cohort differences in all the cognitive performance tests, except for the digit span test and simple movement task in men, the later-born cohort performing better in all the measured outcomes. The results of this study provide strong evidence that cognitive performance is better in more recent cohorts of older people compared to their counterparts measured 28 years earlier.


MiR-92b-3p ameliorates inflammation and autophagy by targeting TRAF3 and suppressing MKK3-p38 pathway in caerulein-induced AR42J cells.
Acute pancreatitis (AP) is an inflammatory disease with high morbidity and mortality. Dysregulation of microRNAs (miRNAs) was involved in human diseases, including AP. However, the effects of miR-92b-3p on AP process and its mechanism remain not been fully clarified. The expression levels of miR-92b-3p and tumor necrosis factor receptor-associated factor-3 (TRAF3) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of TRAF3, tumor necrosis factor α (TNF-α) TNF-α, interleukin-6 (IL-6), phosphorylated mitogen-activated protein kinase kinase 3 (p-MKK3), MKK3, p38 and phosphorylated p38 (p-p38) were detected by western blot. The concentration of TNF-α and IL-6 in the medium was measured using ELISA kits. The possible binding sites of miR-92b-3p and TRAF3 were predicted by TargetScan and verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The expression level of miR-92b-3p was decreased and TRAF3 expression was increased in AR42J cells stimulated with caerulein. Moreover, the protein levels of pro-inflammatory cytokines (TNF-α and IL-6) were markedly elevated, and the expression levels of autophagy-related markers Beclin1 as well as the ratio of LC3-II/I were obviously increased in AR42J cells treated with caerulein. In addition, overexpression of miR-92b-3p or knockdown of TRAF3 significantly suppressed the release of pro-inflammatory cytokines and autophagy in caerulein-induced AR42J cells. Furthermore, TRAF3 was a direct target of miR-92b-3p and its upregulation reversed the effects of miR-92b-3p overexpression on inflammatory response and autophagy. Besides, overexpression of miR-92b-3p inhibited the activation of the MKK3-p38 pathway by affecting TRAF3 expression. In conclusion, miR-92b-3p attenuated inflammatory response and autophagy by downregulating TRAF3 and suppressing MKK3-p38 pathway in caerulein-induced AR42J cells, providing a novel avenue for treatment of AP.


Combination of virtual and experimental 2DE together with ESI LC-MS/MS gives a clearer view about proteomes of human cells and plasma.
Virtual and experimental 2DE coupled with ESI LC-MS/MS was introduced to obtain better representation of the information about human proteome. The proteins from HEPG2 cells and human blood plasma were run by 2DE. After staining and protein spot identification by MALDI-TOF MS, the protein maps were generated. The experimental physicochemical parameters (pI/Mw) of the proteoforms further detected by ESI LC-MS/MS in these spots were obtained. Next, the theoretical pI and Mw of identified proteins were calculated using program Compute pI/Mw (http://web.expasy.org/compute_pi/pi_tool-doc.html). Accordingly, the relationship between theoretical and experimental parameters was analyzed, and the correlation plots were built. Additionally, virtual/experimental information about different protein species/proteoforms from the same genes was extracted. As it was revealed from the plots, the major proteoforms detected in HepG2 cell line have pI/Mw parameters similar to theoretical values. In opposite, the minor protein species have mainly very different from theoretical pI and Mw parameters. A similar situation was observed in plasma in much higher degree. It means that minor protein species are heavily modified in cell and even more in plasma proteome.


Mice lacking d-amino acid oxidase activity exhibit marked reduction of methamphetamine-induced stereotypy.
The behavioral effects induced by methamphetamine (5.0 mg/kg) were compared in the mutant mice lacking d-amino acid oxidase activity and normal mice. The mutant mice exhibited marked decline in the methamphetamine-induced stereotypy compared to the normal mice, whereas the mutant mice displayed a drastic augmentation in the locomotor activity evoked by methamphetamine compared to the normal mice. Because the d-serine levels in the brain of the mutant mice are significantly higher than those in the normal mice, the enhanced d-serine in the brain of the mutant mice could antagonize the methamphetamine-induced stereotypy via the N-methyl-d-aspartate receptors.


Carcinoma of the penis: improved survival by early regional lymphadenectomy based on the histological grade and depth of invasion of the primary lesion.
This study was performed to validate a new staging system and support the concept of early regional lymphadenectomy based on this system. A total of 76 cases from 4 teaching hospitals was reviewed. Of 24 patients with well or moderately differentiated noninvasive primary tumors 1 had regional metastases compared to 43 of 52 patients with poorly differentiated or invasive tumors. By classifying disease according to the depth of invasion and degree of differentiation of the primary lesions a high degree of accuracy could be obtained in predicting the likelihood of positive groin nodes. Removing groin nodes that are microscopically positive improves the survival rate over that of delayed lymphadenectomy.


Preventive knowledge, attitude, and vaccination challenges for COVID-19 among Myanmar refugees and irregular migrants in Malaysia.
Access to vaccinations is crucial for everyone in the fight against the COVID-19 pandemic, regardless of migration or refugee status. This study explored COVID-19 prevention knowledge, attitudes, and vaccination challenges among refugees and irregular migrants from Myanmar in Malaysia. This study employed a descriptive mixed-method approach. Convenience sampling was used to conduct an online survey of 174 participants and two focus groups (N = 14). The majority (51.7 %) were refugees, and 48% were irregular migrant workers. In this study, 90.9% of the participants used social networks and social media chats to obtain information about COVID-19, 84.1% understood and found the vaccination campaign helpful, and 44.2% were aware of it. Although 70% of the participants considered vaccination crucial, 95% said that they would not take it because of fear of arrest and deportation, even though they considered vaccination necessary. Approximately 21.2% of the workers reported that their employers did not provide masks or hand sanitisers. Most of the participants (39.7 %) lived in dormitories provided by their employers. This puts them at a higher risk of infection because of the difficulty in practising social distancing. As part of COVID-19 prevention, the government should grant an amnesty period and work with migrant civil society organisations to administer vaccinations and effective measures for all immigrant populations in Malaysia.


Potentially Preventable Hospitalization Among Adults with Hearing, Vision, and Dual Sensory Loss: A Case and Control Study.
To evaluate the risk of potentially preventable hospitalizations (PPHs) among adults with sensory loss. We hypothesized a greater PPH risk among people with a sensory loss (hearing, vision, and dual) compared with controls. Using 2007-2016 Medicare fee-for-service claims, this retrospective, case-control study examined the risk of PPH among adults aged 65 years and older with hearing, vision, and dual sensory loss compared with their corresponding counterparts without sensory loss (between June 1, 2022, and February 1, 2023). We ran 3 step-in regression models for the 3 case and control cohorts examining PPH risk. Our generalized linear regression models controlled for age, sex, race, Elixhauser comorbidity count, rurality, neighborhood characteristics, and the number of primary care physicians and hospitals at the county level. People with vision (adjusted odds ratio [aOR], 1.21; 95% CI, 0.84-0.87) and dual sensory loss (aOR, 1.26; 95% CI, 1.14-1.40) showed a higher PPH risks than their corresponding controls. For people with hearing loss, our unadjusted models showed a higher PPH risk (OR, 1.40; 95% CI, 1.38-1.43) but after adjustment, hearing loss showed a protective association against PPH risk (OR, 0.85; 95% CI, 0.84-0.87). Moreover, in all models, annual wellness visits reduced the PPH risk by about half (eg, aOR, 0.54; 95% CI, 0.52-0.55), whereas living in disadvantaged neighborhood increased the PPH risk (eg, aOR, 1.13; 95% CI, 1.10-1.15) for cases and controls. People with vision and dual sensory loss were at greater PPH risk. This study has important health policy implications in reducing PPH and is indicative of a need for more incentivized and systematic approaches to facilitating the use of preventive care, particularly among older adults living in a disadvantaged neighborhood.


Effects of GABAB receptor antagonism on the development of pentylenetetrazol-induced kindling in mice.
Pentylenetetrazol (PTZ) administered chronically in rodents induces kindling which is considered to be a model of chronic epilepsy mediated through a specific interaction with the GABA-gated chloride ionophore. PTZ kindling also impairs shuttle-box learning indicating a possible modulation of memory storage [A. Becker, G. Grecksch, H. Mathies. The influence of diazepam on learning processes impaired by pentylenetetrazol kindling. Naunyn-Schmiedeberg's Arch. Pharmacol. 349 (1994) 429-496]. Since GABAB receptor antagonism has been shown to improve cognitive performance in rodents and primates we have examined the effects of 3 antagonists; CGP 36742 (3-amino-propyl-n-butyl-phosphinic acid), CGP 56433 ([3-¿1-(S)-[¿3-(cyclohexylmethyl) hydroxyphosphinyl]-2-(S)-hydroxypropyl]-amino]ethyl]benzoic acid) and CGP 61334 ([3-¿[3[(diethoxymethyl)hydroxyphosphinyl]-propyl-amino¿meth yl]-benzoic acid) on the induction of PTZ kindling in mice at 48 h intervals for 8 weeks. Subsequently the mice were tested in an active avoidance paradigm. At the end of the experiment GABAB receptor autoradiography was performed on brain sections from these animals. Seizure intensity increased progressively in control mice reaching by 8 weeks a mean score which corresponded to clonic seizures. The GABAB antagonists suppressed kindling during the first 4 weeks and after that restored the seizure intensity to the level of control animals. The level of kindling was proportional to the avoidance score. The density of GABAB receptor binding in brain sections from PTZ kindled mice was significantly greater than in controls. This was not altered by pretreatment with the GABAB antagonists except in the cerebellum.


Synthesis, characterization and biological evaluation of dihydropyrimidine derivatives.
A series of dihydropyrimidines containing quinoline were prepared under conventional heating and microwave irradiation. The structures of newly synthesized compounds were established based on analytical and spectral studies. Further these compounds were evaluated for their antioxidant, antifungal and antibacterial activities. Most of the compounds showed moderate to good activity when compared with standard.


Association between e-cigarette use and future combustible cigarette use: Evidence from a prospective cohort of youth and young adults, 2017-2019.
A surge in popularity of e-cigarettes prompts concern given the association between e-cigarettes and future cigarette use. However, much of the evidence for this association comes from early, less efficient, and lower nicotine e-cigarettes than are available and widely used now. The goal of this study was to examine the relationship between e-cigarette use in 2018 and subsequent smoking initiation and continued e-cigarette use. Participants included members of a national longitudinal panel of youth and young adults aged 15-27 who, in 2017, reported never having used a nicotine containing product (n = 3360). Logistic regression analyses assessed associations between participants' self-reported ever e-cigarette use in 2018 and ever cigarette use, current cigarette use, and current e-cigarette use in 2019, after controlling for demographic and psychosocial variables. Compared with those who still had never used an e-cigarette, those who reported ever e-cigarette use in 2018 had significantly higher odds of ever cigarette use (aOR = 7.29, 95% CI [4.10, 12.97]), current cigarette use (aOR = 8.26, 95% CI [3.17, 21.53]), and current e-cigarette use (aOR = 9.70, 95% CI [6.41, 14.69]) one year later in 2019. These findings show that the pod mod style, high nicotine containing e-cigarettes subject young users to the same risks of transitioning to combustible cigarettes as their earlier, less efficient predecessors. Strong regulation of all nicotine products, including e-cigarettes, is needed to prevent the trajectory of e-cigarette to cigarette use among youth and young adults.


Establishment and characterization of a human null-cell lymphoblastic lymphoma cell line (K-LL-3).
A new cell line (K-LL-3) with exceptional characteristics was derived from a bone-marrow aspirate from a patient with poorly differentiated lymphoblastic lymphoma. The cell line was established and the cells maintained on agar feeders for over 1 year. The morphology and cytochemical staining of the primary tumor and the cell line were remarkably similar. The growth characteristics, chromosome pattern, cell-surface receptors and Epstein-Barr pattern, cell-surface receptors and Epstein-Barr virus studies clearly differentiated this cell line from non-malignant lymphoblastoid cell lines. The assay technique used was able to correlate in vitro colony growth with the patient's clinical course. The cells grew on the agar as colonies rather than as a single-cell suspension, and individual colonies could be aspirated and successfully passaged. The K-LL-3 cells lacked cell-surface markers (cytoplasmic and surface immunoglobulins, Fc receptors, C3 receptors, SRBC) except HL-A and thus were classified as null cells. These cells were EBNA (Epstein-Barr virus-specific nuclear antigen) negative and had a pseudodiploid 46XY karyotype.


Medial or lateral location of the whirlpool sign in adnexal torsion: clinical importance.
The whirlpool sign is used as a sonographic marker for adnexal torsion. The aims of this study were to describe the location of the whirlpool sign (lateral or medial to the ovary) and to evaluate the clinical importance of the location. Thirty patients with a confirmed surgical diagnosis of torsion and a positive whirlpool sign on sonography before surgery were included. We examined the sonographic clips of these patients. Classic signs of adnexal torsion were determined: ovarian edema, the presence of a mass, pelvic free fluid, and ovarian ischemia on Doppler imaging. The whirlpool sign was detected on grayscale and color Doppler sonography by moving the transducer to and fro along the axis of suspected torsion. Sixteen of 30 patients had right-sided torsion. Of these, 7 had a lateral whirlpool sign. All 7 of these patients had an ovarian or paraovarian mass. Nine of these 16 patients had a medial whirlpool sign. Of these, 7 had an ovarian or paraovarian mass, and 2 had no mass. Of the 14 patients with left-sided torsion, all had a medial whirlpool sign. Nine of 14 these patients had an ovarian or paraovarian mass, and 5 had no mass. The mean volume of the masses among cases with the lateral whirlpool sign was significantly greater compared to those with the medial whirlpool sign (304 versus 108 cm(3); P = .035). In 25 of 30 cases, the torsed components included the ovary. The lateral whirlpool sign is associated with enlarged masses in comparison to the medial whirlpool sign. This finding indicates the need to search meticulously for the lateral whirlpool sign in cases with enlarged masses to decide whether to operate on these patients emergently.


Psychiatric disorder biomarker discovery using quantitative proteomics.
To date, no molecular biomarker exists for any psychiatric disorder. To identify phenotype-specific biomarkers and investigate the molecular underpinnings of anxiety pathophysiology, we interrogated the well-established mouse model of high (HAB), normal (NAB) and low (LAB) anxiety-related behavior by in vivo (15)N metabolic labeling and quantitative proteomics. The (15)N metabolic labeling approach enables accurate quantification due to the early mixing of the labeled and unlabeled samples under comparison, thus avoiding the biased experimental error introduction during handling. Differentially expressed proteins between HAB and LAB mice can be validated with non-mass-spectrometry-based methods. In silico pathway analysis enables identification of protein networks implicated in anxiety neural circuits. The presented workflow provides a precise and non-hypothesis-driven tool for identifying candidate biomarkers using animal models of psychiatric disorders.


Author Correction: G-tract RNA removes Polycomb repressive complex 2 from genes.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


(De)criminalisation of psychedelics in the Czech Republic-Where are we heading in drug policy and legislation?
The article deals with the issue of decriminalization of drugs, in all relevant contexts, both in terms of criminal policy and legislation, as well as law enforcement, with focus on the Czech Republic. The article proceeds deductively from the general to the specific. First, it discusses the role of law in society and its legitimacy, with focus on legitimate criminal sanctions, which are discussed in the context of the principle of subsidiarity of criminal repression and the principle of opportunity (discretionary prosecution). After these general considerations, the article turns to the issue of drugs and discusses both drug policy and legislation, arguing that the general considerations are in favor of decriminalization tendencies in this area. In the final part, the article focuses on psychedelics, emphasizing a fundamental discrepancy between their factual and legal status and then considering ways of changing the perspective. At this point, the article outlines the importance of decriminalization of psychedelics for therapeutic use, which basically consist of rescheduling of these drugs. The aim of such decriminalization is to make psychedelic-assisted therapy legally available. The article concludes that this is the direction that criminal policy and law in the Czech Republic should take.


Biochemical characterization of "LAP," a polymorphic aminopeptidase from the blue mussel, Mytilus edulis.
A genetically variable naphthylamidase enzyme, previously described as "leucine aminopeptidase," was purified approximately fiftyfold, and its biochemical properties were investigated. The enzyme was renamed "aminopeptidase I." Substrate affinities demonstrate that it is an alpha-aminoacyl peptide hydrolase (E.C. 3.4.11.-). Aminopeptidase I had a monomer molecular weight of 65--68,000, average of pI of pH 4.88, and broad pH optima between 6.5 and 8.0. The enzyme was inactivated rapidly between 40 and 50 C. Antibodies from purified enzyme did not cross-react with other naphthylamidases, but aminopeptidase I activity was inhibited by immune serum. The enzyme exhibited highest naphthylamidase activity for aromatic and hydrophobic aminoacyl naphthylamides. Aminopeptidase activity was highest for aromatic and hydrophobic N-terminal residues of tripeptides. Certain divalent metal cations, p-OH-mercuribenzoate, and N-ethylmaleimide were strongly inhibitory while chelating agents activated the enzyme.


From 3D to 4D printing: a reactor for photochemical experiments using hybrid polyurethane acrylates for vat-based polymerization and surface functionalization.
The vat-based 3D printing of a chemical reactor with flow-meter geometry from an isocyanate-functionalized acrylate monomer followed by post-processing with amino-functionalized photocatalysts is described. This approach results in solvent- and air-stable flow photochemical reactors with UV-A transparent windows that can be applied for photooxygenation and photo redox catalysis.


Synthesis, growth and spectral studies of S-benzyl isothiouronium nitrate by density functional methods.
S-benzyl isothiouronium nitrate (SBTN), was synthesized and characterized by X-ray diffraction, FTIR, UV-Vis and NMR spectra. The Centro-symmetric single crystal of S-benzyl isothiouronium nitrate (SBTN), which crystallizes in monoclinic crystal system with space group P21/C, exhibits second order non-linear optical (NLO) susceptibility, due to intermolecular charge transfer. S-benzyl isothiouronium ion forms well defined charge transfer (CT) salt with anion nitrate through N-H···O and C-H···O hydrogen bonds. It is to identify the direction of specific N-H···O hydrogen bond between the -NH2 group and O(-) in the anion and also sacking in the solid state responsible for NLO activity in this crystal. The SHG technique confirms the non-linear optical property of the grown crystals. Density functional theory (DFT) calculation has been carried out to study the nature of hydrogen involved in the SBTN crystal. The bond lengths and bond angles of the structure of SBTN crystal calculated using B3LYP method with 6-311+(2d,2p) basis set. These calculations are compared with experimental values to provide deep insight into its electronic structure and property of grown crystal.


Temperature-dependent particle number emission rates and emission characteristics during heating processes of edible oils.
The goal of this research is to investigate the temperature-dependent emission rates of particle numbers and emission characteristics during oil heating. Seven regularly used edible oils were studied in a variety of tests to attain this objective. First, total particle number emission rates ranging from 10 nm to 1 μm were measured, followed by an examination within six size intervals from 0.3 μm to 10 μm. Following that, the impacts of oil volume and oil surface area on the emission rate were investigated, and multiple regression models were developed based on the results. The results showed that corn, sunflower and soybean oils had higher emission rates than other oils above 200 °C, with peak values of 8.22 × 109#/s, 8.19 × 109#/s and 8.17 × 109#/s, respectively. Additionally, peanut and rice oils were observed to emit the most particles larger than 0.3 μm, followed by medium-emission (rapeseed and olive oils) and low-emission oils (corn, sunflower and soybean oils). In most cases, oil temperature (T) has the most significant influence on the emission rate during the smoking stage, but its influence was not as pronounced in the moderate smoking stage. The models obtained are all statistically significant (P < 0.001), with R2 values greater than 0.9, and the classical assumption test concluded that regressions were in accordance with the classical assumptions regarding normality, multicollinearity, and heteroscedasticity. In general, low oil volume and large oil surface area were more recommended for cooking to mitigate UFPs emission.


Responses of the coastal bacterial community to viral infection of the algae Phaeocystis globosa.
The release of organic material upon algal cell lyses has a key role in structuring bacterial communities and affects the cycling of biolimiting elements in the marine environment. Here we show that already before cell lysis the leakage or excretion of organic matter by infected yet intact algal cells shaped North Sea bacterial community composition and enhanced bacterial substrate assimilation. Infected algal cultures of Phaeocystis globosa grown in coastal North Sea water contained gamma- and alphaproteobacterial phylotypes that were distinct from those in the non-infected control cultures 5 h after infection. The gammaproteobacterial population at this time mainly consisted of Alteromonas sp. cells that were attached to the infected but still intact host cells. Nano-scale secondary-ion mass spectrometry (nanoSIMS) showed ∼20% transfer of organic matter derived from the infected (13)C- and (15)N-labelled P. globosa cells to Alteromonas sp. cells. Subsequent, viral lysis of P. globosa resulted in the formation of aggregates that were densely colonised by bacteria. Aggregate dissolution was observed after 2 days, which we attribute to bacteriophage-induced lysis of the attached bacteria. Isotope mass spectrometry analysis showed that 40% of the particulate (13)C-organic carbon from the infected P. globosa culture was remineralized to dissolved inorganic carbon after 7 days. These findings reveal a novel role of viruses in the leakage or excretion of algal biomass upon infection, which provides an additional ecological niche for specific bacterial populations and potentially redirects carbon availability.


Impact of limb amputation and cisplatin chemotherapy on metastatic progression in mouse models of osteosarcoma.
Development of animal models that accurately recapitulate human cancer is an ongoing challenge. This is particularly relevant in the study of osteosarcoma (OS), a highly malignant bone tumor diagnosed in approximately 1000 pediatric/adolescent patients each year. Metastasis is the leading cause of patient death underscoring the need for relevant animal models of metastatic OS. In this study, we describe how existing OS mouse models can be interrogated in a time-course context to determine the kinetics of spontaneous metastasis from an orthotopically implanted primary tumor. We evaluated four highly metastatic OS cell lines (3 human, 1 mouse) to establish a timeline for metastatic progression in immune deficient NSG mice. To discern the effects of therapy on tumor development and metastasis in these models, we investigated cisplatin therapy and surgical limb amputation at early and late timepoints. These data help define the appropriate observational periods for studies of metastatic progression in OS and further our understanding of existing mouse models. Efforts to advance the study of metastatic OS are critical for facilitating the identification of novel therapeutics and for improving patient survival.


Perceived benefits and barriers towards exercise among healthcare providers in Ain Shams University Hospitals, Egypt.
Physical inactivity is considered a problem with great impact on morbidity and mortality. There is a necessity to combat this behavior through an assessment of barriers and benefits perceived by subjects. The current study aimed to measure exercise intention, in addition to identifying physical exercise predictors, including perceived barriers and benefits among healthcare providers (HCPs) in Ain Shams University Hospitals. A cross-sectional study was performed on a sample (n = 327) of healthcare providers (physicians and nurses) in Ain Shams University Hospitals in Cairo, Egypt, using anonymous self-administrated questionnaires and relevant scales. Out of 327 healthcare providers approached, 52.6% of them were males and the mean age of participants was (29.34 ± 7.84 years). Physical exercise was reported by 44.6% of participants. The most significant factors associated with physical exercise engagement were male gender, participants with lower body mass index (BMI), and those with higher perceived "life enhancement subscale" benefit score and lower perceived exercise milieu and physical exertion barriers subscale scores. Exercisers showed significantly higher total overall (benefits and barriers) score compared to non-exercisers. Physicians showed a significantly higher total score compared to nurses. The prevalence of regular exercise is low and inversely related to the female gender, BMI, Exercise milieu, and Physical exertion barriers subscale scores, and directly related to life enhancement benefit subscale score. Health education program about the benefits and barriers of exercise is recommended to encourage healthcare personnel to follow a healthy lifestyle as a role model to their patients and to act as health promoters to them.


Toll-like receptor 2 is at least partly involved in the antitumor activity of glycoprotein from Chlorella vulgaris.
Toll-like receptors (TLR) are involved in innate immunity by recognizing various bacterial components. We have previously reported that an active substance of ARS-2 purified from the culture medium of Chlorella vulgaris was a glycoprotein with a molecular weight of 63,100 amu and that this glycoprotein expressed antitumor activity, with the protein moiety in ARS-2 being necessary for this antitumor activity. Here, we show that ARS-2 stimulated spleen-adherent cells from C3H/HeJ lacking functional TLR4 to produce interleukin-12 (IL-12) p40, whereas such cytokine production was significantly impaired in ARS-2-stimulated spleen-adherent cells from TLR2 knockout mice. The overexpression of mouse TLR2 (mTLR2) and mouse CD14 (mCD14) conferred the ARS-2 inducibility of nuclear factor-kappaB activation to human HEK 293 cells. These results suggest that TLR2 signaling is at least partly involved in the antitumor activity of the water-soluble antitumor glycoprotein from C. vulgaris.