Effect of the irreversible aromatase inhibitor FCE 24304 on DMBA-induced mammary tumors in ovariectomized rats treated with testosterone.
The antitumor activity of the irreversible aromatase inhibitor FCE 24304 (6-methylenandrosta-1,4-diene-3,17-dione) was studied in ovariectomized, testosterone propionate (TP)-treated rats with 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumors that were used as a postmenopausal tumor model. When given s.c. at 20 mg/kg per day, 3 days a week for 4 weeks, TP was effective in maintaining tumor growth in ovariectomized rats (51% tumor regression in control animals vs 94% in ovariectomized rats). FCE 24304 given s.c. twice daily at 100 mg/kg per day, 6 days a week for 4 weeks, induced 96% regression, thus inhibiting the growth-promoting effect of TP. When the effect of various doses of FCE 24304 was evaluated, in comparison with a 52% tumor regression rate in control (ovariectomized, TP-treated) rats, tumor regressions amounted to 88% and 96% at s.c. FCE 24304 doses of 10 and 50 mg/kg per day, respectively, and to 76%, 88%, and 81% at oral doses of 10, 50, and 100 mg/kg per day, respectively. When FCE 24304 was given alone to ovariectomized rats, it did not affect ovariectomy-induced tumor regression (87% vs 94%). In conclusion, FCE 24304 was effective by both the s.c. and oral routes against DMBA-induced mammary tumors in ovariectomized TP-treated rats, a postmenopausal mammary tumor model.


Antitumoral and antimetastatic effects of metronomic chemotherapy with cyclophosphamide combined with celecoxib on murine mammary adenocarcinomas.
Metronomic chemotherapy (MCT) refers to the chronic and equally spaced administration of low doses of different chemotherapy drugs, without extended interruptions. Previously, we demonstrated the antitumor effect of MCT with cyclophosphamide (Cy) in a mouse mammary adenocarcinoma model. Herein, we investigated the therapeutic efficacy of metronomic Cy combined with celecoxib (Cel) in two murine mammary adenocarcinoma models. Mice were s.c. challenged with M-234 p or M-406 mammary tumors and from day 5 or 8 on, respectively, treated with: (I) no treatment (controls); (II) Cy in the drinking water (25-30 mg/kg body weight/day); (III) Cel (30 mg/kg p.o.), five times/week; (IV) treated as II + III. Mice challenged i.v. with M-234 p or M-406 tumor cells received, on day 3, the same treatments. We found that MCT with Cy plus Cel inhibited tumor growth decreased lung metastases, and increased the median survival time, in both tumor models, having very low toxicity. MCT with Cy combined with Cel was more effective than each monotherapy. The therapeutic benefits of combined MCT with cyclophosphamide plus celecoxib on mammary adenocarcinomas together with its very low toxicity profile warrant further study in an attempt to make the translation into the clinic.


Elimination of polyamine N-acetylation and regulatory engineering improved putrescine production by Corynebacterium glutamicum.
Corynebacterium glutamicum has been engineered for production of the polyamide monomer putrescine or 1,4-diaminobutane. Here, N-acetylputrescine was shown to be a significant by-product of putrescine production by recombinant putrescine producing C. glutamicum strains. A systematic gene deletion approach of 18 (putative) N-acetyltransferase genes revealed that the cg1722 gene product was responsible for putrescine acetylation. The encoded enzyme was purified and characterized as polyamine N-acetyltransferase. The enzyme accepted acetyl-CoA and propionyl-CoA as donors for acetylation of putrescine and other diamines as acceptors, but showed highest catalytic efficiency with the triamine spermidine and the tetraamine spermine and, hence, was named SnaA. Upon deletion of snaA in the putrescine producing strain PUT21, no acteylputrescine accumulated, but about 41% more putrescine as compared to the parent strain. Moreover, a transcriptome approach identified increased expression of the cgmAR operon encoding a putative permease and a transcriptional TetR-family repressor upon induction of putrescine production in C. glutamicum PUT21. CgmR is known to bind to cgmO upstream of cgmAR and gel mobility shift experiments with purified CgmR revealed that putrescine and other diamines perturbed CgmR-cgmO complex formation, but not migration of free cgmO DNA. Deletion of the repressor gene cgmR resulted in expression changes of a number of genes and increased putrescine production of C. glutamicum PUT21 by 19% as compared to the parent strain. Overexpression of the putative transport gene cgmA increased putrescine production by 24% as compared to the control strain. However, cgmA overexpression in PUT21ΔsnaA did not further improve putrescine production, hence, the beneficial effects of both targets were not synergistic at the highest described yield of 0.21 g g(-1).


Disulfide locked variants of factor VIIa with a restricted beta-strand conformation have enhanced enzymatic activity.
Proteolytic processing of zymogen Factor VII to Factor VIIa (FVIIa) is necessary but not sufficient for maximal proteolytic activity, which requires an additional allosteric influence induced upon binding to its cofactor tissue factor (TF). A key conformational change affecting the zymogenicity of FVIIa involves a unique three-residue shift in the position of beta-strand B2 in their zymogen and protease forms. By selectively introducing new disulfide bonds, we locked the conformation of these strands into an active TF*FVIIa-like state. FVIIa mutants designated 136:160, 137:159, 138:160, and 139:157, reflecting the position of the new disulfide bond (chymotypsinogen numbering), were expressed and purified by TF affinity chromatography. Mass spectrometric analysis of tryptic peptides from the FVIIa mutants confirmed the new disulfide bond formation. Kinetic analysis of amidolytic activity revealed that all FVIIa variants alone had increased specific activity compared to wild type, the largest being for variants 136:160 and 138:160 with substrate S-2765, having 670- and 330-fold increases, respectively. Notably, FVIIa disulfide-locked variants no longer required TF as a cofactor for maximal activity in amidolytic assays. In the presence of soluble TF, activity was enhanced 20- and 12-fold for variants 136:160 and 138:160, respectively, compared to wild type. With relipidated TF, mutants 136:160 and 137:159 also had an approximate threefold increase in their V(max)/K(m) values for FX activation but no significant improvement in TF-dependent clotting assays. Thus, while large rate enhancements were obtained for amidolytic substrates binding at the active site, macro-molecular substrates that bind to FVIIa exosites entail more complex catalytic requirements.


Urinary Dickkopf-3 and Contrast-Associated Kidney Damage.
Administration of iodinated contrast medium (CM) during invasive cardiovascular procedures may be associated with impairment of kidney function. Urinary dickkopf-3 (DKK3), a stress-induced renal tubular epithelium-derived glycoprotein, has been identified as a biomarker predicting both acute kidney injury (AKI) and persistent kidney dysfunction. Urinary DKK3/creatinine ratio (uDKK3/uCr), urine and serum neutrophil gelatinase-associated lipocalin (uNGAL, sNGAL) and serum cystatin C (sCyC) were assessed in 458 patients with chronic kidney disease scheduled for invasive cardiovascular procedures requiring CM administration with universal adoption of nephroprotective interventions. Contrast-associated AKI (CA-AKI) was defined as serum creatinine increase ≥0.3 mg/dl at 48 h after CM administration. Persistent kidney dysfunction was defined as persistent estimated glomerular filtration rate reduction ≥25% at 1 month compared with baseline. CA-AKI occurred in 64 or the 458 patients (14%), and baseline uDKK3/uCr ≥491 pg/mg was the best threshold for its prediction. Net reclassification improvement (NRI) was significantly increased by adding baseline uDKK3/uCr to the Mehran, Gurm, and National Cardiovascular Data Registry (NCDR) scores (all p < 0.05), and the same applied to integrated discrimination improvement (IDI) when adding uDKK3/uCr to the Gurm and NCDR scores (p < 0.001). Persistent kidney dysfunction occurred in 57 of the 458 patients (12%) and baseline uDKK3/uCr ≥322 pg/mg appeared as the best threshold for its prediction. Adding baseline uDKK3/uCr to the Mehran, Gurm, and NCDR scores significantly increased IDI and NRI (all p < 0.001). Baseline uDKK3/uCr seems to be a reliable marker for improving the identification of patients with chronic kidney disease undergoing invasive coronary and peripheral procedures at risk for AKI and persistent kidney dysfunction.


Effect of a 6-month school-based physical activity program on body composition and physical fitness in lean and obese schoolchildren.
Few studies have investigated the impact of school-based physical activity interventions on anthropometric characteristics concomitantly with aerobic and anaerobic capacities in young children. The present study aimed to assess the effect of a 6-month physical activity program on body composition and physical fitness among primary schoolchildren. Four hundred fifty-seven children aged 6 to 10 years were randomly assigned to the intervention group (229 children) or observational group (228 children). Participants' height and weight were assessed, and obesity was determined using French reference curves for BMI. The sum of the four skinfolds and fat-free mass were determined. Ground tests were used to assess aerobic (20-m shuttle run test) and anaerobic (cycling peak power) fitness before and after a 6-month physical activity intervention. The anthropometric modifications obtained over the 6 months cannot be attributed to the intervention as the ANOVA revealed no group effect (intervention vs. group). However, anaerobic and aerobic fitness were significantly improved, thanks to the program in both lean and obese children. A 6-month school-based physical activity intervention in 6- to 10-year-old children did not yield positive anthropometric improvements, but appears effective in terms of aerobic and anaerobic physical fitness. Two physical activity sessions per week in addition to standard physical education classes in primary schoolchildren bring effective results for the prevention of childhood obesity.


What drives the decoupling between economic growth and energy-related CO2 emissions in China's agricultural sector?
Many studies have shown that the rapid agricultural mechanization development in China led to substantial energy consumption and CO2 emission growth. To better explain the mechanism behind the decoupling between economic growth and CO2 emissions, this paper extends the logarithmic mean Divisia index (LMDI) and production-theoretical decomposition (PDA) considering agricultural decoupling from both structural and technical perspectives. The results reveal that (1) China's agricultural decoupling performance was not ideal. Investment and investment efficiency were the most important factors influencing the decoupling status. The main decoupling obstacle was a higher investment in productivity rather than in energy conservation and carbon reduction. (2) The decoupling status and investment orientation of decoupling efforts among regions were different. Strong negative decoupling statuses frequently occurred in the eastern region, whose main disadvantage was high potential energy intensity. The decoupling status of the central region exhibited expansive features. The decoupling key is to invest more in energy-saving technology rather than in production. The western region changed from weak decoupling to expansive negative decoupling. Both output technology and energy-related factors should be the main investment targets. (3) Weak decoupling and expansive negative decoupling were the most common statuses among provinces. The influence mechanism of drivers exhibited a high spatial heterogeneity at the provincial level. Therefore, the study offered a convincing basis for local governments to formulate low-carbon agricultural development policies by identifying the main decoupling drivers.


Soft dendritic microparticles with unusual adhesion and structuring properties.
The interplay between morphology, excluded volume and adhesivity of particles critically determines the physical properties of numerous soft materials and coatings1-6. Branched particles2 or nanofibres3, nanofibrillated cellulose4 or fumed silica5 can enhance the structure-building abilities of colloids, whose adhesion may also be increased by capillarity or binding agents6. Nonetheless, alternative mechanisms of strong adhesion found in nature involve fibrillar mats with numerous subcontacts (contact splitting)7-11 as seen in the feet of gecko lizards and spider webs12-17. Here, we describe the fabrication of hierarchically structured polymeric microparticles having branched nanofibre coronas with a dendritic morphology. Polymer precipitation in highly turbulent flow results in microparticles with fractal branching and nanofibrillar contact splitting that exhibit gelation at very low volume fractions, strong interparticle adhesion and binding into coatings and non-woven sheets. These soft dendritic particles also have potential advantages for food, personal care or pharmaceutical product formulations.


Corrigendum to "Depression, anxiety, and stress mediate the associations between internet gaming disorder, insomnia, and quality of life during the COVID-19 outbreak" [Addict. Behav. Rep. 12 (2020) 100307].
[This corrects the article DOI: 10.1016/j.abrep.2020.100307.].


Exploiting bioactive natural products of marine origin: Evaluation of the meroterpenoid metachromin V as a novel potential therapeutic drug for colorectal cancer.
Colorectal cancer (CRC) is the second most common cause of cancer death, leading to almost 1 million deaths per year. Despite constant progress in surgical and therapeutic protocols, the 5-year survival rate of advanced CRC patients remains extremely poor. Colorectal Cancer Stem Cells (CRC-CSCs) are endowed with unique stemness-related properties responsible for resistance, relapse and metastasis. The development of novel therapeutics able to tackle CSCs while avoiding undesired toxicity is a major need for cancer treatment. Natural products are a large reservoir of unexplored compounds with possible anticancer bioactivity, sustainability, and safety. The family of meroterpenoids derived from sponges share interesting bioactive properties. Bioassay-guided fractionation of a meroterpenoids extract led to the isolation of three compounds, all cytotoxic against several cancer cell lines: Metachromins U, V and W. In this study, we evaluated the anticancer potential of the most active one, Metachromins V (MV), on patient-derived CRC-CSCs. MV strongly impairs CSCs-viability regardless their mutational background and the cytotoxic effect is maintained on therapy-resistant metastatic CSCs. MV affects cell cycle progression, inducing a block in G2 phase in all the cell lines tested and more pronouncedly in CRC-CSCs. Moreover, MV triggers an important reorganization of the cytoskeleton and a strong reduction of Rho GTPases expression, impairing CRC-CSCs motility and invasion ability. By Proteomic analysis identified a potential molecular target of MV: CCAR1, that regulates apoptosis under chemotherapy treatments and affect β-catenin pathway. Further studies will be needed to confirm and validate these data in in vivo experimental models.


Pharmacovigilance network as an additional tool for the surveillance of antimicrobial resistance.
The WHO Programme for International Drug Monitoring (PIDM) is a large Pharmacovigilance network of countries sharing Adverse Drug Reaction (ADR) reports. Pharmacovigilance Experts have suggested that antimicrobial resistance (AMR) is an overlooked adverse event. We undertook this study to investigate the potential role of Pharmacovigilance databases in the surveillance of AMR. Using the AWaRe (Access, Watch and Reserve) list and the WHO Priority Pathogens List, we established a list of antimicrobials and carried out a VigiBase search via VigiAccess, looking for ADR reports with Preferred Terms (PTs) that contained AMR-relevant information. Identified Terms were matched with codes from the Medical Dictionary for Regulatory Activities (MedDRA Version 21.1). Records on 86 drugs were retrieved with a total of 1 170 751 ADR reports submitted between 1968 and 2018. Seventeen PTs suggesting suspected resistance, ineffectiveness, inappropriate use, or medication error were used to code 15 250 reports. The most frequently used PTs were "Drug Ineffective" (45.6%), "Off label use" (9.5%) and "Pathogen Resistance" (8.9%). A group of six agents (Amoxicillin, Cefalotin, Ciprofloxacin, Clarithromycin, Levofloxacin and Daptomycin) accounted for 38% (n = 5806) of all 15 250 AMR-relevant ADR reports. The PTs most frequently used in 5806 reports were grouped in 4 categories: drug ineffectiveness (62.5%), resistance (19.2%), off-label use (12.1%) and prescription errors (6.2%). Our findings suggest that Pharmacovigilance databases could serve as a tool in tracking antimicrobial use and resistance especially in settings where laboratory capacity is still in its development stages. National Pharmacovigilance centers could play a proactive role in stimulating the reporting of AMR-relevant ADRs which can serve as a basis for resistance suspicion alerts. Further studies focusing on the narrative and other clinical pharmacology details in ADR reports are required.


Weighted norm inequalities for multilinear Calderón-Zygmund operators in generalized Morrey spaces.
In this paper, the authors study the boundedness of multilinear Calderón-Zygmund singular integral operators and their commutators in generalized Morrey spaces.


Can Individualized-Targeted Computerized Cognitive Training Benefit Adults with HIV-Associated Neurocognitive Disorder? The Training on Purpose Study (TOPS).
Half of people with HIV (PWH) have HIV-associated neurocognitive disorder (HAND). This study examined whether cognition can be improved using a framework targeting impaired individual cognitive domains in PWH with HAND. In this two-group pre-post experimental design study, 88 adults with HAND were randomized to either: (1) a no-contact control group (n = 40) or (2) the Individualized-Targeted Cognitive Training group (n = 48). Baseline cognitive performance was assessed on eight cognitive domains. A theoretical framework was used to determine the two cognitive domains selected for training. With priority on speed of processing (SOP) and attention impairments, participants received SOP and/or attention training if such impairments were detected; if not, participants were assigned to cognitive training in one/two of the least impaired cognitive domains contributing to their HAND diagnosis. Global cognitive score was slightly improved following training (p = 0.256; d = - 0.21), but it was not significant. Significant improvements were observed on SOP following training in that domain (SOP; d = - 0.88; p = 0.011). SOP training also improved functioning in other cognitive domains. This individualized cognitive intervention did not change HAND status, but it did result in improved SOP, in turn yielding improvement in other cognitive domains.


Abnormal resting brain activity in patients with functional dyspepsia is related to symptom severity.
Abnormal processing of visceral sensation at the level of the central nervous system is believed to be involved in functional dyspepsia. However, compared with studies of stimulation-related changes in brain activity, few studies have focused on resting brain activity, which also is important in pathogenesis. We mapped changes in resting brain glucometabolism of patients with functional dyspepsia, compared with healthy subjects, and attempted to correlate abnormal brain activity with symptom severity. We performed fluorodeoxyglucose positron emission tomography-computed tomography on 40 patients with functional dyspepsia and 20 healthy subjects who were in resting states. The symptom index of dyspepsia and the Nepean dyspepsia index were used to determine symptom severity. The positron emission tomography-computed tomography data were analyzed using statistical parametric mapping software. Compared with healthy subjects, patients with functional dyspepsia had higher levels of glycometabolism in the bilateral insula, anterior cingulate cortex (ACC), middle cingulate cortex (MCC), cerebellum, thalamus, prefrontal cortex, precentral gyrus, postcentral gyrus, middle temporal gyrus, superior temporal gyrus, putamen, right parahippocampal gyrus, claustrum, and left precuneus (P < .001). The signal increase in the ACC, insula, thalamus, MCC, and cerebellum was correlated with symptom index of dyspepsia scores and Nepean dyspepsia index scores (P < .01). The glycometabolism in ACC, insula, thalamus, MCC, and cerebellum of patients with more severe functional dyspepsia was significantly higher than that of patients with less severe functional dyspepsia (P < .005). In patients with functional dyspepsia, resting cerebral glycometabolism differs significantly from that of healthy subjects. The ACC, insula, thalamus, MCC, and cerebellum might be the key regions that determine the severity of symptoms.


Thermoelectric properties of rare-earth doped Fe2VAl Heusler alloys.
The low-temperature electrical transport properties of the rare-earth (RE) Ce, Dy, Sm element doped Fe2VAl Heusler alloys have been investigated. A significant enhancement in the Seebeck coefficient S (peak values of about -125 to -160 μV K-1) is observed as compared to the pure Fe2VAl (peak value of about 40 μV K-1). It is observed that the thermal conductivity reduced by 50% in RE-doped samples. The single parabolic band model has been used to analyze the experimental data and to understand the role of fundamental parameters like the Lorenz number. The lattice contribution to the total thermal conductivity was analyzed through the Callaway model, which in turn provided the insight into the phonon scattering in these alloys. Finally, we demonstrate a significant improvement in power factor and figure of merit at all temperatures for the RE-doped Fe2VAl alloys.


The 2021 WHO Classification of Tumors of the Central Nervous System: An update on pediatric low-grade gliomas and glioneuronal tumors.
The 2021 5th edition of the WHO Classification of Tumors of the Central Nervous System reflects the discovery of genetic alterations underlying many central nervous system (CNS) neoplasms. Insights gained from technologic advances and novel applications in molecular diagnostics, including next-generation sequencing and DNA methylation-based profiling, coupled with the recognition of clinicopathologic correlates, have prompted substantial changes to CNS tumor classification; this is particularly true for pediatric low-grade gliomas and glioneuronal tumors (pLGG/GNTs). The 2021 WHO now classifies gliomas, glioneuronal tumors and neuronal tumors into 6 families, three of which encompass pLGG/LGNTs: "Pediatric type diffuse low-grade gliomas," "circumscribed astrocytic gliomas," and "glioneuronal and neuronal tumors." Among these are six newly recognized tumor types: "diffuse astrocytoma, MYB or MYBL1-altered"; "polymorphous low grade neuroepithelial tumor of the young (PLNTY)"; "diffuse low-grade glioma-MAPK altered"; "Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC)"; "myxoid glioneuronal tumor (MGT)"; and "multinodular and vacuolating neuronal tumor (MVNT)." We review these newly recognized entities in the context of general changes to the WHO schema, discuss implications of the new classification for treatment of pLGG/LGNT, and consider strategies for molecular testing and interpretation.


Sediment contact test with Potamopyrgus antipodarum in effect-directed analyses-challenges and opportunities.
Effect-directed analysis is increasingly used for the identification of key toxicants in environmental samples and there is a growing need for in vivo biotests as diagnostic tools. Within this study, we performed an in vivo sediment contact test, applicable on both native field samples and their extracts or fractions, in order to be able to compare the results from both field and laboratory studies. A sediment contact test with the prosobranch snail, Potamopyrgus antipodarum, was carried out on extracts and fractions of field sediments from three European river basins. The results were compared with previous results of the native field samples. In contrast to the native sediments, the extracts of the samples led to an overall decrease in reproduction. Even the chosen reference sites had an adverse effect on the snails' reproduction. It appeared that a higher bioavailability in the organic extracts, together with a changing composition of compounds could have lead to this change in effects. The fractionation of the extracts partly led to a more differentiated picture, but the resolution was not high enough to see any distinct effects on the snails' reproduction. Our results highlight the importance of the use of in vivo biotests and point out the relevance of bioavailability in native sediments. For further fractionation studies, a more realistic extraction procedure, together with a higher resolution fractionation, would be appropriate in order to separate individual bioavailable compounds more efficient.


Potentiation of bradykinin action on smooth muscle by a scorpion venom extract.
Gel filtration of the water extract of the venom of the scorpion T. serrulatus showed four peaks; the first peak (P1) is devoid of toxic activity but increases the bradykinin-induced contraction of isolated rat uterus and guinea-pig ileum. The stepwise fractionation of the pooled P1 peak was performed in a DEAE-cellulose column and the bradykinin potentiating activity was found in the second protein peak. Finger-printing of this material showed that the bradykinin potentiating material migrates to the anode, giving two spots when submitted to chromatography, the activity being found in the spot that presents the greatest Rf. The potentiator is destroyed by heating at 97 degrees C, is not dialysable and is destroyed by incubation with pronase. Some of these properties differentiate it from the BPF's from snake venoms.


Thoroughly Validated Bayesian Estimator and Limited Sampling Strategy for Dose Individualization of Ganciclovir and Valganciclovir in Pediatric Transplant Recipients.
Given a high pharmacokinetic inter-individual variability and a low exposure target achievement, ganciclovir (GCV) therapeutic drug monitoring is sometimes used in children. We aimed to develop and validate Bayesian estimators based on limited sampling strategies for the estimation of GCV area under the concentration-time curve from 0 to 24 h in pediatric transplant recipients treated with valganciclovir (VGCV) or GCV. Solid organ transplant or stem-cell transplant recipients who received GCV or VGCV and had available GCV concentrations per standard of care were retrospectively included in this study for pharmacokinetic modeling and development of Bayesian estimators using the iterative two-stage Bayesian method. Validation datasets included additional child recipients of a solid organ transplant or stem-cell transplant, and child recipients of a kidney or liver transplant enrolled in a previous study. Various combinations of three or two sampling times, applicable in clinical practice, were assessed based on the relative mean bias, standard deviation, and the root mean square error in a development dataset and three independent validation datasets. In the development dataset, the mean bias/standard deviation/root mean square error for the 1 h/2 h/3 h and 1 h/3 h limited sampling strategies were - 1.4%/9.3%/9.1% and - 3.5%/12.2%/12.3%, respectively for GCV, while for VGCV, the mean bias/standard deviation/root mean square error for the 1 h/2 h/6 h and 1 h/6 h limited sampling strategies were 0.7%/13.5%/13.3% and - 0.1%/12.1%/11.8%, respectively. In the independent validation datasets, seven (13%) and five (14%) children would have had misclassifications of their exposure using these Bayesian estimators and limited sampling strategies for VGCV and GCV, respectively. Three plasma samples collected at 1 h/2 h/3 h and 1 h/2 h/6 h post-dose for GCV and VGCV respectively, are sufficient to accurately determine GCV area under the concentration-time curve from 0 to 24 h for pharmacokinetic-enhanced therapeutic drug monitoring.


Development of Calibration Models to Predict Mean Fibre Diameter in Llama (Lama glama) Fleeces with Near Infrared Spectroscopy.
Llama fibre has the potential to become the most valuable textile resource in the Puna region of Argentina. In this study near infrared reflectance spectroscopy was evaluated to predict the mean fibre diameter in llama fleeces. Analyses between sets of carded and non-carded samples in combination with spectral preprocessing techniques were carried out and a total of 169 spectral signatures of llama samples in Vis and NIR ranges (400-2500 nm) were obtained. Spectral preprocessing consisted in wavelength selection (Vis-NIR, NIR and discrete ranges) and multiplicative and derivative pretreatments; spectra without pretreatments were also included, while modified partial least squares (M-PLS) regression was used to develop prediction models. Predictability was evaluated through R2: standard cross validation error (SECV), external validation error (SEV) and residual predictive value (RPD). A total of 54 calibration models were developed in which the best model (R2 = 0.67; SECV = 1.965; SEV = 2.235 and RPD = 1.91) was obtained in the Vis-NIR range applying the first derivative pretreatment. ANOVA analysis showed differences between carded and non-carded sets and the models obtained could be used in screening programs and contribute to valorisation of llama fibre and sustainable development of textile industry in the Puna territory of Catamarca. The data presented in this paper are a contribution to enhance the scarce information on this subject.


Expression analysis of cell cycle related lncRNAs in breast cancer tissues.
Cell cycle regulation is an important cellular function. Abnormal regulation of this process can cause cancer. Several genes are involved in this process. There is no comprehensive study on expression pattern of cell cycle related lncRNAs in breast cancer patients. In the current study, we evaluated expressions of LINC00668, PRDM16-DT, SNHG7 and CDKN2A in 42 pairs of breast cancer tissues and adjacent non-tumoral tissues. Expression of SNHG7 was significantly lower in tumoral tissues compared with non-tumoral tissues. However, expressions of LINC00668, PRDM16-DT and CDKN2A were not significantly different between these two sets of samples. Expression levels of SNHG7 could separate tumoral tissues from non-tumoral tissues with AUC value= 0.66, sensitivity= 61% and specificity= 73%. Expression of CDKN2A was associated with clinical stage (P value=0.01). Expression levels of LINC00668, PRDM16-DT, SNHG7 and CDKN2A were higher in estrogen receptor (ER) positive samples compared with ER negative ones (P values=0.044, 0.008, 0.002 and 0.022, respectively). Moreover, expression of SNHG7 was higher in progesterone receptor (PR) positive samples compared with PR negative ones (P value=0.02). Finally, expressions of PRDM16-DT, SNHG7 and CDKN2A were higher in HER2/neu positive samples compared with HER2/neu negative ones (P values=0.017, 0.02 and 0.021, respectively). Taken together, our study demonstrates possible roles of these genes in breast cancer and warrants further functional studies.


The Short-Term Effects of Roux-en-Y Gastric Bypass on Renal Excretion of Sodium and Its Association with Blood Pressure.
Bariatric surgery has been shown to be effective in reducing weight and has benefits, such as lowering blood pressure. An increase in urinary sodium excretion has been suggested as a possible mechanism. This study explored changes in sodium excretion and their correlation with blood pressure after Roux-en-Y gastric bypass. This study was conducted on 28 obese participants with body mass index (BMI) of 44.54 ± 7.81 kg/m2 who underwent gastric bypass. Before surgery and at the third and sixth months after gastric bypass, blood pressure, urinary sodium concentration, 24-hour (24-h) urinary sodium excretion, and fractional excretion of sodium were evaluated. In addition, serum sodium and potassium levels were determined. Nonparametric tests were used to analyze the data. Blood pressure decreased after surgery and remained at low levels over the 3- and 6-month periods. The urinary sodium concentration increased at 3 months after surgery; however, the 24-h urinary sodium excretion and urine volume decreased. Interestingly, although some associations between variables were observed, significant correlations between the 24-h urinary sodium excretion and the systolic, diastolic, and mean blood pressures were found. In addition, the urine volume was higher in the sixth month than in the third month following surgery. In the months immediately following surgery, a low-salt and low-volume diet favors decreases in urine volume and 24-h urinary sodium excretion. In addition, in the sixth month after surgery, an association between blood pressure and 24-h urinary sodium excretion was observed.


LncRNA ITGB2-AS1 promotes the progression of clear cell renal cell carcinoma by modulating miR-328-5p/HMGA1 axis.
Clear cell renal cell carcinoma (ccRCC) is the most common histologic subtype of renal cell carcinoma and long non-coding RNAs (lncRNAs) play important roles in the progression of ccRCC. In this study, we aim to explore the potential function of ITGB2-AS1 in ccRCC progression and its underlying molecular mechanism. We first explored the association between ITGB2-AS1 expression level and ccRCC prognosis. We found that the expression level of ITGB2-AS1 was significantly higher in ccRCC tumor and cell lines, and highly expressed ITGB2-AS1 was also associated with a poorer prognosis. Consistently, silencing ITGB2-AS1 inhibited proliferation, promoted apoptosis in ccRCC cell lines, and curbed the tumorigenesis in the Xenograft model, reduced tumorigenesis in a xenograft tumor growth model. We further identified and confirmed the miRNA miR-328-5p as a target of ITGB2-AS1, and miR-328-5p negatively regulated the expression of HMGA1 protein. The anti-tumor effect of silencing ITGB2-AS1 could be partially rescued by inhibiting miR-328-5p activity or overexpressing HMGA1, indicating that ITGB2-AS1 promotes the survival and progression of ccRCC by modulating miR-328-5p/HMGA1 axis. Collectively, our data demonstrated that ITGB2-AS1 expression level is positively correlated with the survival and tumorigenesis of ccRCC. As a target of ITGB2-AS1, miR-328-5p seems to function as a tumor-suppressor, and the oncogenic effect of ITGB2-AS1 is partially mediated via the miR-328-5p/HMGA1 axis.


Acute appendicitis: prospective evaluation of a diagnostic algorithm integrating ultrasound and low-dose CT to reduce the need of standard CT.
To evaluate an algorithm integrating ultrasound and low-dose unenhanced CT with oral contrast medium (LDCT) in the assessment of acute appendicitis, to reduce the need of conventional CT. Ultrasound was performed upon admission in 183 consecutive adult patients (111 women, 72 men, mean age 32) with suspicion of acute appendicitis and a BMI between 18.5 and 30 (step 1). No further examination was recommended when ultrasound was positive for appendicitis, negative with low clinical suspicion, or demonstrated an alternative diagnosis. All other patients underwent LDCT (30 mAs) (step 2). Standard intravenously enhanced CT (180 mAs) was performed after indeterminate LDCT (step 3). No further imaging was recommended after ultrasound in 84 (46%) patients; LDCT was obtained in 99 (54%). LDCT was positive or negative for appendicitis in 81 (82%) of these 99 patients, indeterminate in 18 (18%) who underwent standard CT. Eighty-six (47%) of the 183 patients had a surgically proven appendicitis. The sensitivity and specificity of the algorithm were 98.8% and 96.9%. The proposed algorithm achieved high sensitivity and specificity for detection of acute appendicitis, while reducing the need for standard CT and thus limiting exposition to radiation and to intravenous contrast media.


Hippocampal lesions are without effect on olfactory memory formation in the context of pregnancy block.
Female mice which have mated and are subsequently exposed to male urine odours (pheromones), which differ from those of the male that mated (stud male), undergo hormonal changes resulting in a block to pregnancy. Since the stud male's odour blocks the pregnancy of females other than those he mated, this would suggest that a memory specific for this male's odour is established at the time of mating. Hippocampal lesions, when made prior to mating, did not disrupt memory formation to the odour of the stud male. This male's odour did not block pregnancy, while changing odour to that of the strange male did block pregnancy. In order to establish the functional effectiveness of these hippocampal lesions, olfactory discriminations were examined in a modified T-maze. The odour discrimination was urine-soiled bedding taken from a cage of different strain males versus same strain bedding. After 35 trials, neither control nor lesioned females were performing above chance level (50% correct responses), indicating the difficulty in cognitively learning this discrimination. These female mice were therefore trained to distinguish a novel odour (butyl acetate) from familiar strain urine-soiled bedding. Hippocampal-lesioned females were slower to acquire this discrimination and did not perform above chance level after 35 trials, in contrast to the 70% success of sham-lesioned females. Hence, hippocampal lesions, while producing a deficit in olfactory learning in the maze test, are without effect on the formation or retrieval of the specific olfactory memory formed for the stud male at mating, as revealed from pregnancy block tests.


Disseminated Mycobacterium genavense infection in a FIV-positive cat.
An 8-year-old FIV-positive Australian cat was presented with coughing, periocular alopecia, pyrexia and inappetence. Skin scrapings demonstrated Demodex cati mites. Antibiotics were administered and it was treated successfully for periocular demodectic mange, but the cat continued to exhibit respiratory signs and lose weight. Further investigation revealed an ascarid infection and active chronic inflammation of undetected cause affecting the lower airways. Repetitive treatment with pyrantel failed to eradicate the ascarid infection. The cat became cachectic and developed moist ulcerative dermatitis of the neck, severe non-regenerative anaemia, leucopenia and thrombocytopenia. Necropsy and histopathology revealed mycobacteriosis affecting skin, lungs, spleen, lymph nodes, liver and kidney. Attempted culture of frozen tissues at a mycobacteria reference laboratory was unsuccessful. Paraffin-embedded, formalin-fixed tissue was retrieved and examined using PCR to amplify part of the 16S rRNA gene. A diagnosis of disseminated Mycobacterium genavense infection was made based on the presence of acid fast bacteria in many tissues and partial sequence of the 16S rRNA gene. Although M genavense has been identified previously as a cause of disseminated disease in AIDS patients, this is the first report of infection in a cat. It was suspected that the demodecosis, recurrent ascarid infections and disseminated M genavense infection resulted from an immune deficiency syndrome consequent to longstanding FIV infection.


Endurance test selection optimized via sample size predictions.
Selecting the most appropriate performance test is critical in detecting the effect of an intervention. In this investigation we 1) used time-trial (TT) performance data to estimate sample size requirements for test selection and 2) demonstrated the differences in statistical power between a repeated-measures ANOVA (RM-ANOVA) and analysis of covariance (ANCOVA) for detecting an effect in parallel group design. A retrospective analysis of six altitude studies was completed, totaling 105 volunteers. We quantified the test-retest reliability [i.e., intraclass correlation coefficient (ICC) and standard error of measurement (SEM)] and then calculated the standardized effect size for a 5-20% change in TT performance. With these outcomes, a power analysis was performed and required sample sizes were compared among performance tests. Relative to TT duration, the 11.2-km run had the lowest between-subject variance, and thus greatest statistical power (i.e., required smallest sample size) to detect a given percent change in performance. However, the 3.2-km run was the most reliable test (ICC: 0.89, SEM: 81 s) and thus better suited to detect the smallest absolute (i.e., seconds) change in performance. When TT durations were similar, a running modality (11.2-km run; ICC: 0.83, SEM: 422 s) was far more reliable than cycling (720-kJ cycle; ICC: 0.77, SEM: 480 s). In all scenarios, the ANCOVA provided greater statistical power than the RM-ANOVA. Our results suggest that running tests (3.2 km and 11.2 km) using ANCOVA analysis provide the greatest likelihood of detecting a significant change in performance response to an intervention, particularly in populations unaccustomed to cycling.NEW & NOTEWORTHY This is the first investigation to utilize time-trial (TT) data from previous studies in simulations to estimate statistical power. We developed an easy-to-use decision aid detailing the required sample size needed to detect a given change in TT performance for the purpose of test selection. Furthermore, our detailed methods can be applied to any scenario in which there is an impact of a stressor and the desire to detect a treatment effect.


Comparative cradle-to-grave life cycle assessment of biogas production from marine algae and cattle manure biorefineries.
The environmental impacts resulting from the cradle-to-grave life cycles of Enteromorpha prolifera macroalgae and cattle manure biorefineries are assessed and compared. Sensitivity analysis is carried out to evaluate the response of the impacts to changes in biogas application by using Simapro 7.3.3. Three scenarios are considered in the biorefineries. In the first and second scenarios, the biogas produced is considered to be used for electricity production and transportation, respectively. In the third scenario, the biogas is considered to be recycled back to the systems. Process energy requirements and transportation of inputs contribute the largest share of the overall impacts. The cattle manure biorefinery is slightly more eco-friendly than the macroalgae biorefinery in Scenarios 1 and 2 because it requires more eco-friendly inputs. However, the macroalgae biorefinery becomes more eco-friendly than the cattle manure biorefinery in Scenario 3 because macroalgae require less energy and water for biogas production.


Reduced maternal serum concentrations of angiopoietin-2 in the first trimester precede intrauterine growth restriction associated with placental insufficiency.
The aim of this study was to investigate whether maternal serum levels of angiopoietin-2 (Ang-2) and pregnancy-associated plasma protein A (PAPP-A) are associated with subsequent intrauterine growth restriction (IUGR). Ang-2 was measured in 29 nonpregnant and 44 pregnant women at 10-13 weeks of gestation. The median concentration of Ang-2 was 26.61 ng/ml in normal pregnant women compared with 1.71 ng/ml in nonpregnant controls (P < 0.01). Women who subsequently developed severe IUGR had lower levels of Ang-2 compared with normal pregnant controls (P < 0.01). PAPP-A levels were similar in all pregnant groups. These findings suggest that Ang-2 should be evaluated for its ability to predict pregnancies that later are affected by IUGR.


Trypanosoma cruzi seroprevalence and associated factors in women in Casanare-Colombia.
Chagas disease is caused by the parasite Trypanosoma cruzi and transmitted mainly by triatomines and from mothers to children. In Colombia, this disease is a public health problem and due to its high endemicity and vertical transmission, women are susceptible populations that must be evaluated. Our objective was to determinate the Trypanosoma cruzi seroprevalence and factors associated with women in Pore (Municipality), Casanare, Colombia. Cross-sectional study. A sample of 230 healthy volunteer women, 15 years or older, without previous diagnosis of Chagas disease was taken; the serological analysis was done using the Chagas ELISA IgG and IgM and indirect Hemagglutination (HAI) technique. In addition, a survey was applied to each participant in order to explore the presence of factors that could be associated with a positive test result. The seropostitivity found in Pore Casanare's women was 16.9% (39/230, 95% CI 12.1-21.7), additionally it was found that rural origin, the coexistence with animals, especially chickens, age, low level schooling and housing material are factors associated with T. cruzi infection in this population. The results of this study indicate the importance of conducting extensive seroepidemiological studies in populations of endemic areas, due to the difficulty in detecting cases in the acute phase; therefore, screening allows the establishment of a follow-up and treatment time line that contributes to the interruption of the transmission vertical.


End Group Properties of Thiols Affecting the Self-Assembly Mechanism at Gold Nanoparticles Film As Evidenced by Water Infrared Probe.
Water infrared probe has been employed for in situ monitoring of the detailed self-assembly processes of four thiol molecules with different end groups (-CH3, -NH2, -COOH, and -OH) on gold nanoparticles (Au NPs) film in aqueous solution. Based on the change of water IR signal, the significant influence of end group properties on the kinetics and thermodynamics of thiols self-assembly can be estimated. It is found that the assembly kinetics of thiols decreases with the increase of the hydrophobicity of the end groups. In addition, the charges carried by the end groups (-COOH and -NH2 terminated thiols) will also slow down the self-assembly kinetics owing to the electrostatic repulsions. However, the isothermal adsorption is only affected by the wettability of the end groups of thiols. The higher hydrophilicity of the end groups results in larger equilibrium constant of the self-assembly process. Results show that water infrared probe offers an additional approach to the monitoring of thiols self-assembly processes with higher sensitivity and more detailed information as compared to traditional molecule fingerprints.


Membrane Fractionation by Isopycnic Sucrose Density Gradient Centrifugation for Qualitative Analysis of LPS in Escherichia coli.
Gram-negative diderm bacteria are characterized by a tripartite cell envelope, composed of an inner membrane (IM) and a lipopolysaccharide (LPS)-containing outer membrane (OM), separated by an aqueous space where the peptidoglycan is embedded. LPS is a peculiar glycolipid endowed with several biological activities. The biosynthesis and transport of LPS to its final location take place in every compartment of the cell envelope. Proteins and protein machineries with different subcellular localization are involved in this process to facilitate the trafficking of LPS across subcellular compartments that differ in their physicochemical proprieties. The fractionation of bacterial cell envelopes can give information on the status of the LPS biogenesis by allowing the analysis of LPS profiles and of the localization of proteins involved in the transport. Here, we describe a standardized protocol for membrane fractionation in Escherichia coli using sucrose density gradient centrifugation that separates the IM from the OM cellular fractions. Bacterial cells are first converted into spheroplasts and lysed; then the membrane fractions are collected by ultracentrifugation and separated at high speed by exploiting the differences in membrane density. The fractions obtained are analyzed for LPS total amount and electrophoretic profile.


Reduced regional cerebral blood flow in patients with heart failure.
Heart failure (HF) patients show significant lateralized neural injury, accompanied by autonomic, mood and cognitive deficits. Both gray and white matter damage occurs and probably develops from altered cerebral blood flow (CBF), a consequence of impaired cardiac output. However, the distribution of regional CBF changes in HF patients is unknown, but is an issue in determining mechanisms of neural injury. Our aim was to compare regional CBF changes in HF with CBF in control subjects using non-invasive pseudo-continuous arterial spin labelling (ASL) procedures. We collected pseudo-continuous ASL data from 19 HF patients [mean age 55.5 ± 9.1 years; mean body mass index 27.7 ± 5.3 kg/m2 ; 13 male) and 29 control subjects (mean age 51.4 ± 5.3 years; mean body mass index 25.7 ± 3.6 kg/m2 ; 18 male), using a 3.0-Tesla magnetic resonance imaging (MRI) scanner. Whole-brain CBF maps were calculated, normalized to a common space, smoothed and compared between groups using ANCOVA (covariates; age, gender and gray matter volume). Reduced CBF appeared in multiple sites in HF patients in comparison with controls, with principally lateralized lower flow in temporal, parietal and occipital regions. Areas with decreased CBF included the bilateral prefrontal, frontal, temporal and occipital cortex, thalamus, cerebellum, corona radiate, corpus callosum, hippocampus and amygdala. Heart failure patients showed lower, and largely lateralized, CBF in multiple autonomic, mood and cognitive regulatory sites. The reduced CBF is likely to contribute to the lateralized brain injury, leading to the autonomic and neuropsychological deficits found in the condition.


Assessing exercise capacity, quality of life and haemodynamics in heart failure: do the tests tell us the same thing?
The objective measurement of exercise tolerance is an important component of heart failure trials. The use of laboratory-based treadmill exercise testing has attracted criticism, however, as being unrepresentative of patients' true capabilities. To examine the relationships between tests of exercise capacity, quality of life and haemodynamics in patients with stable symptomatic heart failure. Thirty-six patients with mild-moderate chronic heart failure were studied. Exercise capacity was assessed in the laboratory by maximal treadmill tests and self-paced corridor walk tests, and in the patients' homes by hip-borne pedometers. Quality of life was assessed by a disease-specific questionnaire. Cardiac output and limb blood flow were measured by non-invasive techniques. Customary activity as assessed by pedometer scores correlated with quality of life questionnaire scores (r(S) = 0.47, P = 0.04), and both variables correlated with limb (calf) blood flow (pedometer scores: r(S) = 0.39, P = 0.03; quality of life scores: r(S)= 0.50, P = 0.04). The laboratory-based maximal treadmill test correlated with the self-paced corridor walk test, but neither of these tests correlated with pedometer scores, quality of life or haemodynamics. Different methods of assessing exercise capacity do not appear to give comparable results and bear different relationships to haemodynamic variables and quality of life. Pedometer scores of customary activity may better reflect patients' quality of life and appear to be more closely related to limb blood flow than the maximal treadmill exercise test or the corridor walk test. The sole use of laboratory-based exercise tests in therapeutic trials may give a misleading assessment of treatment efficacy in heart failure patients.


[Quality of life in osteomuscular chronic pain].
To value the quality of life of the patients with osteomuscular chronic pain users of two Primary Care Centres, by means of the application of questionnaire COOP-WONCA adapted to the Spanish during the second semester of 2003 and first of 2004. Cross-sectional observational descriptive design. Systematic random sample. 320 users of the Health Centres of Puerto de Sagunto (Valencia) and Alto Palancia (Castellón) that suffer chronic pain of osteomuscular origin. Collection of data from the application of Questionnaire COOP-WONCA adapted to Spanish. The subjective perception of health of the great majority of our population is regular or bad. Greater deterioration of the physical state than of the mental one. Badly pharmacologic control of pain. The musculoskeletal chronic pain has a noticeable repercussion on the quality of life.


Diarrheal illness in a cohort of children 0-2 years of age in rural Bangladesh: I. Incidence and risk factors.
To describe clinical characteristics and age- and season-specific incidences of diarrheal episodes, and to evaluate risk factors associated with the occurrence of diarrheal disease. A total of 252 infants from rural Bangladesh were followed through household surveillance for 2 y from birth during the years 1993-1996. Demographic and household determinants were linked to the probability of illness using logistic regression models. The overall incidence of diarrhea was 4.25 episodes per child per year. Peak rates of overall, acute, and persistent diarrhea occurred in the 6-11-mo and 12-17-mo age groups. Diarrheal rates peaked during the spring and summer. Among host-related characteristics, having a sibling in the household and having had prior diarrhea were significant risk factors for diarrhea. Among environmental characteristics, spring season remained a highly statistically significant risk factor for diarrhea. Diarrheal disease continues to be a substantial burden in young children in rural Bangladesh. Most diarrheal episodes are of short duration, and should primarily be treated with oral rehydration therapy to prevent diarrhea-related mortality. Improved knowledge of oral rehydration therapy, feeding during episodes to prevent further malnutrition, prolonged breastfeeding, and the keeping of livestock in corralled areas of the home are advocated.


Deep learning-based automatic tumor burden assessment of pediatric high-grade gliomas, medulloblastomas, and other leptomeningeal seeding tumors.
Longitudinal measurement of tumor burden with magnetic resonance imaging (MRI) is an essential component of response assessment in pediatric brain tumors. We developed a fully automated pipeline for the segmentation of tumors in pediatric high-grade gliomas, medulloblastomas, and leptomeningeal seeding tumors. We further developed an algorithm for automatic 2D and volumetric size measurement of tumors. The preoperative and postoperative cohorts were randomly split into training and testing sets in a 4:1 ratio. A 3D U-Net neural network was trained to automatically segment the tumor on T1 contrast-enhanced and T2/FLAIR images. The product of the maximum bidimensional diameters according to the RAPNO (Response Assessment in Pediatric Neuro-Oncology) criteria (AutoRAPNO) was determined. Performance was compared to that of 2 expert human raters who performed assessments independently. Volumetric measurements of predicted and expert segmentations were computationally derived and compared. A total of 794 preoperative MRIs from 794 patients and 1003 postoperative MRIs from 122 patients were included. There was excellent agreement of volumes between preoperative and postoperative predicted and manual segmentations, with intraclass correlation coefficients (ICCs) of 0.912 and 0.960 for the 2 preoperative and 0.947 and 0.896 for the 2 postoperative models. There was high agreement between AutoRAPNO scores on predicted segmentations and manually calculated scores based on manual segmentations (Rater 2 ICC = 0.909; Rater 3 ICC = 0.851). Lastly, the performance of AutoRAPNO was superior in repeatability to that of human raters for MRIs with multiple lesions. Our automated deep learning pipeline demonstrates potential utility for response assessment in pediatric brain tumors. The tool should be further validated in prospective studies.


Treatment of Acute Myeloid Leukemia with the FLT3 Gene Mutation.
In acute myeloid leukemia (AML), mutations of the Fms-like tyrosine kinase 3 receptor (FLT3) and its overexpression are related with hyperleukocytosis, higher risk of relapse, and decrease of both disease-free survival and overall survival. It has been suggested that this phenomenon confers proliferative and survival advantages to the malignant blast cells. As a consequence, it is an attractive therapeutic target. As the best treatment strategy for mutated FLT3 AML remains to be defined, the addition of FLT3 inhibitor drugs to chemotherapy or to the bone marrow transplant approach has become a growing strategy. With encouraging results, this combination seems to be an attractive option. Relevant data regarding the current treatment trends on mutated FLT3 AML is reviewed here.


Iron chelation for the treatment of uveitis.
Inflammatory eye diseases such as uveitis are common and may eventually result in vision loss. Iron can play a critical role in ocular inflammation via promoting the generation of oxygen free radicals and it is also nutritionally essential for microbial growth. Considering this involvement of iron in inflammation and microbial infection, we hypothesize that administration of iron chelators has potential to function as a novel therapy in uveitis and help improve clinical outcomes.


Multi-response optimization toward efficient and clean (co-)combustions of textile dyeing sludge and second-generation feedstock.
The rapid growth of textile dyeing sludge (TDS) necessitates feeding it back into a circular economy in an efficient and clean way. This study aimed to optimize the clean and efficient operational conditions to co-combust TDS and incense sticks (IS). The (co-)-combustions exhibited four distinctive stages of thermal degradation. According to the master-plots method, the reaction mechanisms of reaction order (F2.4 and F1.5), three-dimensional diffusion (D3), and nucleation growth (A1.5) best explained the four stages, respectively. The interaction between TDS and IS exerted an inhibition effect in the range of 400-500 °C and a facilitation effect in the range of 600-1000 °C. At 300 °C as the main reaction temperature, the main evolved gas and functional groups such as CO2, H2O, CH4, C˭O, C-O, and C-H were detected. The addition of IS improved the comprehensive combustion index, inhibited SO2, but enhanced CO2, HCN, and NOx emissions. CaO in IS enabled Fe to remain in TDS and fixed more S in ash. Multi-response optimizations based on the best-fit artificial neural networks revealed the range of 545-605 °C and the co-combustion of 25% TDS and 75% IS as the cleaner and more efficient operational conditions.


Radiation dose to technicians per nuclear medicine procedure: comparison between technetium-99m, gallium-67, and iodine-131 radiotracers and fluorine-18 fluorodeoxyglucose.
The aim of this study was to determine the non-extremity gamma dose received by a technician while performing an ordinary nuclear medicine procedure or a static (i.e. without blood sampling) fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) study. The dose per patient was measured by means of a commercial electronic pocket Geiger Mueller dosimeter, worn in the upper left pocket of the overalls. This was previously tested by exposure to known point sources of technetium-99m, gallium-67, iodine-131 and fluorine-18 in the air. A further test was performed with 99mTc, 131I and 18F sources inserted in a water phantom to simulate the condition of high scattering degradation of the primary radiation due to the patient's tissues. Subsequently, the dose was measured by two technicians for a total of 314 clinical cases, covering the most common nuclear medicine procedures, including 44 static, two-level FDG PET studies with repositioning of the patient on the couch between the transmission and the emission scan and seven whole-body PET studies. The dose read by the dosimeter was corrected for environmental background and for detector efficiency measured with sources in the air. For a limited subset of cases, the time spent close to patients was also measured. Doses were then estimated by a crude non-absorbing point source approximation and by using experimental dose rates. A comparison between experimental and estimated doses, as well as with previously published data, completed the work. For most of the conventional procedures, the measured dose per procedure proved to be within the range 0.2-0.4 microSv, except for equilibrium angiocardioscintigraphy (1.0+/-0.5 microSv) and 99mTc-sestamibi single-photon emission tomography (1. 7+/-1.0 microSv). Comparison with data published in the last 20 years shows that our values are generally lower. The current more favourable working conditions are a result of technological improvements (for instance two-head gamma cameras capable of whole-body studies), and safer shielding and distance from patients. Two-level PET gave 11.5+/-4.4 microSv and whole-body PET 5.9+/-1.2 microSv. In a subset of patients these values could be subdivided into the separate contributions from each phase of the procedure. They were: 0.11+/-0.04 microSv for daily quality assurance, 2.9+/-3.0 microSv for two transmission scans, 0.3+/-0.1 microSv for syringe preparation, 2.8+/-1.8 microSv for injection and escorting the patient to the waiting room, 1.7+/-1.5 microSv for a whole-body emission scan, 7.7+/-5.2 microSv for two emission scans, and 0.8+/-0. 2 microSv for patient departure. The higher value from PET by comparison with conventional procedures is attributable to the higher specific gamma constant of 18F, as well as the longer time required for accurate positioning.


Differential expression of spleen tyrosine kinase Syk isoforms in tissues: Effects of the microbial flora.
Spleen tyrosine kinase (Syk) is expressed widely in hematopoietic and non-hematopoietic cells. The widespread distribution of Syk and its involvement in host defense and allergic reactions, prompted us analyze the influence of microbial exposure on Syk expression. We compared the distribution of Syk in various tissues of germ-free and conventional mice using immunohistochemistry, Western blot analysis and real time RT-PCR. Total Syk expression was similar between germ-free and conventional mice. Since it has been claimed that Syk isoforms are differentially expressed, we studied the distribution and abundance of Syk (L) and Syk (S) isoforms in tissues from these mice. In contrast to previous reports, we found broad tissue expression of Syk (S). Interestingly, in germ-free mice the amount of Syk (S) but not Syk L protein was selectively increased in lung and spleen. In summary, our study reveals new and broad tissue expression of both Syk isoforms and demonstrates that lack of microbial flora results in selectively increased expression of Syk (S) isoform in lung and spleen.


Pharmacokinetics of topically applied cyclopentolate HCl and tropicamide.
The time course of accommodative loss after the topical application of 0.5% and 1.0% concentrations of cyclopentolate HCl and tropicamide was measured over a 20-min interval in 50 age- and sex-matched subjects between 20 and 30 years of age. Computer-assisted measures of residual accommodation provided detailed data on the temporal aspects of the cycloplegia induced by these commonly utilized drugs when used alone or with the topical anesthetic proparacaine HCl. The pattern of recovery of ocular accommodation from cycloplegia was also measured over a 5-h period, starting 2 h after drug application. The results show that latency, depth of cycloplegia, and rate of accommodative loss are regulated to drug type and concentration, and are influenced by the iris coloration of the test eye. The rate of onset of cycloplegia was not accelerated in blue or brown irides by the preadministration of proparacaine. Regardless of iris pigmentation, recovery from tropicamide cycloplegia was much faster than recovery from cyclopentolate cycloplegia. In contrast, the depth of cyclopentolate cycloplegia present in brown irides during the recovery phase was much greater than in blue irides. Mechanisms to explain these observations are proposed and clinical implications of these findings are presented.


Global cellular changes induced by Legionella pneumophila infection of bone marrow-derived macrophages.
The nucleotide-binding oligomerization domain (Nod)-like receptor (NLR) family member Naip5 plays an essential role in restricting Legionella pneumophila growth inside primary macrophages. Upon interaction with bacterial flagellin, the intracellular receptor Naip5 forms a multi-protein complex, the inflammasome, which activation has a protective role against infection. The A/J mouse strain carries a Naip5 allele (Naip5(A/J)), which renders its macrophages susceptible to Legionella infection. However, Naip5(A/J) is still competent for inflammasome activation suggesting that an as yet unidentified signaling pathway located downstream of Naip5 and defective in Naip5(A/J) macrophages regulates macrophage defenses against Legionella. Therefore, transcriptional profiling experiments with macrophages from C57BL/6J mice (B6), and from congenic mice (BcA75) carrying the partial loss-of-function A/J-derived allele (Naip5(A/J)) on a B6 background, infected or not with wild-type L. pneumophila or flagellin-deficient mutant were carried out to identify genes regulated by flagellin and by Naip5. Both the Legionella infection per se and the presence of flagellin had very strong effects on transcriptional responses of macrophages, 4h following infection, including modulation of cellular pathways associated with inflammatory response and cell survival. On the other hand, the presence of wild type or partial loss of function allele (Naip5(A/J)) at Naip5 did not cause large effects on transcriptional responses of macrophages to infection. We also examined in L. pneumophila infected macrophages, the effect of Naip5 alleles on expression and phosphorylation of 524 phosphoproteins, kinases and phosphatases involved in cell proliferation, immune response, stress and apoptosis. Naip5 alleles had an effect on the TLR-Il1R signaling pathway, the cell cycle and the caveolin-mediated response to pathogen. The results of transcriptome and proteome analyses were organized into cellular pathways in macrophages that are modulated in response to Legionella infection.


Molecular control limiting sensitivity of sweet taste neurons in Drosophila.
To assess the biological value of environmental stimuli, animals' sensory systems must accurately decode both the identities and the intensities of these stimuli. While much is known about the mechanism by which sensory neurons detect the identities of stimuli, less is known about the mechanism that controls how sensory neurons respond appropriately to different intensities of stimuli. The ionotropic receptor IR76b has been shown to be expressed in different Drosophila chemosensory neurons for sensing a variety of chemicals. Here, we show that IR76b plays an unexpected role in lowering the sensitivity of Drosophila sweet taste neurons. First, IR76b mutants exhibited clear behavioral responses to sucrose and acetic acid (AA) at concentrations that were too low to trigger observable behavioral responses from WT animals. Second, IR76b is expressed in many sweet neurons on the labellum, and these neurons responded to both sucrose and AA. Removing IR76b from the sweet neurons increased their neuronal responses as well as animals' behavioral responses to sucrose and AA. Conversely, overexpressing IR76b in the sweet neurons decreased their neuronal as well as animals' behavioral responses to sucrose and AA. Last, IR76b's response-lowering ability has specificity: IR76b mutants and WT showed comparable responses to capsaicin when the mammalian capsaicin receptor VR1 was ectopically expressed in their sweet neurons. Our findings suggest that sensitivity of Drosophila sweet neurons to their endogenous ligands is actively limited by IR76b and uncover a potential molecular target by which contexts can modulate sensitivity of sweet neurons.


Leveraging Research Synthesis Methods to Support Evidence-Based Policy- and Decision-Making.
This commentary discusses the potential utility of research syntheses for evidence-based policy- and decision-making, examining the papers that comprise the special issue on modern meta-analytic methods. Evidence and data have the potential to play a critical role in the development of policies and in the administration of programs that meet the social and economic needs of children and families. Novel, innovative, and methodologically rigorous methods that allow for comprehensive and systematic research synthesis, such as those disseminated in this special issue, can help inform the work of the federal government and the prevention science field at large. Overall, the papers hold promise for strengthening the rigor of existing approaches, illustrate novel approaches, and demonstrate the utility of information that research syntheses can produce. Collectively, the studies in this special issue advance the available toolbox of methods that can be used to support evidence-based policy- and decision-making.


SCAR R&D Symposium 2003: comparing the efficacy of 5-MP CRT versus 3-MP LCD in the evaluation of interstitial lung disease.
The efficacy of two medical-grade, self-calibrating, gray scale displays were compared with regard to impact on sensitivity and specificity for the detection of interstitial lung disease (ILD) on computed radiographs (CR). The displays were a 5-megapixel (MP) cathode ray tube (CRT) device and a 3-MP liquid crystal display (LCD). A sample consisting of 230 anteroposterior (AP), posteroanterior (PA), and lateral views of the chest with CT-proven findings characteristic for ILD as well as 80 normal images were compared. This double-blinded trial produced a sample sufficient to detect if the sensitivity of the LCD was 10% or more reduced (one-sided) from the "gold standard" CRT display. Both displays were calibrated to the DICOM gray scale standard and the coefficient of variation of the luminance function varied less than 2% during the study. Five board-certified radiologists specializing in thoracic radiology interpreted the sample on both displays and the intraobserver Az (area under the ROC curve) showed no significant correlation to the display used. In addition, an interobserver kappa analysis showed that the relative disagreement between any observer pair remained relatively constant between displays, and thus was display invariant. This study demonstrated there is no significant change in observer performance sensitivity on 5-MP CRT versus 3-MP LCD displays for CR examinations demonstrating ILD of the chest.


The death pathways in mussel larval cells after a freeze-thaw cycle.
We analyzed cell viability, caspase activity, plasma membrane alterations and cell ultrastructure morphology to estimate the morphological and biochemical alterations that occur in bivalve molluscan cell cultures during cryopreservation. The use of 5% dymethyl sulfoxide as a cryoprotectant resulted in greater cell survival and a scarcity of destroyed cells lacking cytosol among dead cells. In this case, almost all cells died through necrosis or apoptosis, which appeared to increase in mussel cell cultures after a freeze-thaw cycle. Apoptosis was not a main death pathway in mussel cells, but it was induced in a significant part of these cells (up to 24%) immediately after thawing and depended mostly on the cryoprotectant used. Regardless of the type of the used cryoprotectant, we observed some nuclear aberrations in cells after freezing-thawing, such as few multipolar mitoses or the absence of a division spindle in mitotic cells. After analyzing different methods for assessing cell damage, the best results were obtained from optimal approaches that could provide information regarding the cell disruption level after freezing-thawing and could be considered for future studies.


Associations between excessive fatigue and pain, sleep, mental-health and work factors in Norwegian nurses.
To investigate whether pain, sleep duration, insomnia, sleepiness, work-related factors, anxiety, and depression associate with excessive fatigue in nurses. Fatigue among nurses is a problem in the context of ongoing nursing shortages. While myriad factors are associated with fatigue not all relationships are understood. Prior studies have not examined excessive fatigue in the context of pain, sleep, mental health, and work factors in a working population to determine if associations between excessive fatigue and each of these factors remain when adjusting for each other. A cross-sectional questionnaire study among 1,335 Norwegian nurses. The questionnaire included measures for fatigue (Chalder Fatigue Questionnaire, score ≥4 categorized as excessive fatigue), pain, sleep duration, insomnia (Bergen Insomnia Scale), daytime sleepiness (Epworth Sleepiness Scale), anxiety and depression (Hospital Anxiety and Depression Scale), and work-related factors. Associations between the exposure variables and excessive fatigue were analyzed using chi-square tests and logistic regression analyses. In the fully adjusted model, significant associations were found between excessive fatigue and pain severity scores for arms/wrists/hands (adjusted OR (aOR) = 1.09, CI = 1.02-1.17), hips/legs/knees/feet (aOR = 1.11, CI = 1.05-1.18), and headaches/migraines (aOR = 1.16, CI = 1.07-1.27), sleep duration of <6 hours (aOR = 2.02, CI = 1.08-3.77), and total symptom scores for insomnia (aOR = 1.05, CI = 1.03-1.08), sleepiness (aOR = 1.11, CI = 1.06-1.17), anxiety (aOR = 1.09, CI = 1.03-1.16), and depression (aOR = 1.24, CI = 1.16-1.33). The musculoskeletal complaint-severity index score (aOR = 1.27, CI = 1.13-1.42) was associated with excessive fatigue in a separate model adjusted for all variables and demographics. Excessive fatigue was also associated with shift work disorder (OR = 2.25, CI = 1.76-2.89) in a model adjusted for demographics. We found no associations with shift work, number of night shifts and number of quick returns (<11 hours between shifts) in the fully adjusted model. Excessive fatigue was associated with pain, sleep- and mental health-factors in a fully adjusted model.


Evaluation of Hospital Cesarean Delivery-Related Profits and Rates in the United States.
A high cesarean delivery rate in US hospitals indicates the potential overuse of this procedure; however, underlying causes of the excessive use of cesarean procedures in the US have not been fully understood. To investigate the association between the probability of cesarean delivery at the patient-level and profit per procedure from cesarean deliveries. This observational, cross-sectional study used a nationally representative sample of hospital discharge data from women at low risk for cesarean birth who delivered newborns between 2010 and 2014 in the US. Data were gathered from the Nationwide Readmissions Database from the Healthcare Cost and Utilization Project, compiled by the Agency for Healthcare Research and Quality. Data cleaning and analyses were conducted between August 2019 and May 2020. Hospital-level median value of profits from cesarean deliveries, defined as the difference between the charge and the cost for cesarean delivery calculated for each hospital. Our primary outcome was the individual-level probability of undergoing a cesarean delivery. We examined the association with the hospital-level median value of profits per procedure for cesarean delivery (defined as the difference between the charge and the cost for cesarean delivery) using hierarchical regression models adjusted for patient and hospital characteristics and year-fixed effects. A total of 13 215 853 deliveries were included in our analyses (mean [SE] age, 27.4 [0] years), of which 2 202 632 (16.7%) were cesarean deliveries. After adjusting for potential confounders, pregnant women were more likely to have a cesarean birth when they delivered at hospitals with higher profits per procedure from cesarean deliveries. Women cared for at hospitals with the highest (adjusted odds ratio, 1.08; 95% CI, 1.02-1.14; P = .005) and second-highest profit quartiles (adjusted odds ratio, 1.07; 95% CI, 1.02-1.13; P = .007) had higher probabilities of a cesarean delivery compared with those cared for at hospitals in the lowest profit quartile. In this cross-sectional study of US nationally representative hospital discharge data, hospitals with higher profits per cesarean procedure were associated with an increased probability of delivering newborns through cesarean birth. These findings highlight the potential influence financial incentives play in determining a high cesarean delivery rate in the US.


Alzheimer's disease: Insights and new prospects in disease pathophysiology, biomarkers and disease-modifying drugs.
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases that affect millions of people worldwide, with both prevalence and incidence increasing with age. It is characterized by cognitive decline associated, specifically, with degeneration of cholinergic neurons. The problem of this disease is even more fundamental as the available therapies remain fairly limited and mainly focused on symptoms' relief. Although the aetiology of the disease remains elusive, two main pathological hallmarks are described: i) presence of neurofibrillary tangles formed by unfolded protein aggregates (hyperphosphorylated Tau protein) and ii) presence of extracellular aggregates of amyloid-beta peptide. Given the complexity surrounding the pathogenesis of the disease, several potential targets have been highlighted and interrelated upon its progression, such as oxidative stress and the accumulation of metal ions. Thus, advances have been made on the development of innovative multitarget therapeutical compounds to delay the disease progression and restore cell function. This review focuses the ongoing research on new insights and emerging disease-modifying drugs for AD treatment. Furthermore, classical and novel potential biomarkers for early diagnosis of the disease, and their role in assisting on the improvement of targeted therapies will also be approached.


Acetic Acid Ketonization over Fe3O4/SiO2 for Pyrolysis Bio-Oil Upgrading.
A family of silica-supported, magnetite nanoparticle catalysts was synthesised and investigated for continuous-flow acetic acid ketonisation as a model pyrolysis bio-oil upgrading reaction. The physico-chemical properties of Fe3O4/SiO2 catalysts were characterised by using high-resolution transmission electron microscopy, X-ray absorption spectroscopy, X-ray photo-electron spectroscopy, diffuse reflectance infrared Fourier transform spectroscopy, thermogravimetric analysis and porosimetry. The acid site densities were inversely proportional to the Fe3O4 particle size, although the acid strength and Lewis character were size-invariant, and correlated with the specific activity for the vapour-phase acetic ketonisation to acetone. A constant activation energy (∼110 kJ mol-1), turnover frequency (∼13 h-1) and selectivity to acetone of 60 % were observed for ketonisation across the catalyst series, which implies that Fe3O4 is the principal active component of Red Mud waste.


European Association of Urology Section of Urolithiasis and International Alliance of Urolithiasis Joint Consensus on Percutaneous Nephrolithotomy.
Although percutaneous nephrolithotomy (PCNL) has been performed for decades and has gone through many refinements, there are still concerns regarding its more widespread utilization because of the long learning curve and the potential risk of severe complications. Many technical details are not included in the guidelines because of their nature and research protocol. To achieve an expert consensus viewpoint on PCNL indications, preoperative patient preparation, surgical strategy, management and prevention of severe complications, postoperative management, and follow-up. An international panel of experts from the Urolithiasis Section of the European Association of Urology, International Alliance of Urolithiasis, and other urology associations was enrolled, and a prospectively conducted study, incorporating literature review, discussion on research gaps (RGs), and questionnaires and following data analysis, was performed to reach a consensus on PCNL. The expert panel consisted of 36 specialists in PCNL from 20 countries all around the world. A consensus on PCNL was developed. The expert panel was not as large as expected, and the discussion on RGs did not bring in more supportive evidence in the present consensus. Adequate preoperative preparation, especially elimination of urinary tract infection prior to PCNL, accurate puncture with guidance of fluoroscopy and/or ultrasonography or a combination, keeping a low intrarenal pressure, and shortening of operation time during PCNL are important technical requirements to ensure safety and efficiency in PCNL. Percutaneous nephrolithotomy (PCNL) has been a well-established procedure for the management of upper urinary tract stones. However, according to an expert panel consensus, core technical aspects, as well as the urologist's experience, are critical to the safety and effectiveness of PCNL.


The identification of a neutral glycosphingolipid antigenic marker for metastatic cells in the R3230AC rat mammary adenocarcinoma.
The process of metastasis is a complex process involving numerous steps, and it is thought that cells able to complete all of these steps and form metastatic foci form a unique subpopulation of cells within the tumor. To study this metastatic subpopulation, a marker for the metastatic cells is required. We have previously described the enrichment of soybean agglutinin binding cells in tumor populations enriched for lymphatic metastasis [1]. In this study we provide evidence that the cell-surface structure binding soybean agglutinin is a neutral glycosphingolipid. Using monoclonal antibodies generated against this glycolipid, highly metastatic tumor populations were depleted of cells containing this glycolipid. These depleted cell populations were found to be equally tumorigenic to that of the untreated population but were much less metastatic. These results suggest that this glycolipid may be a useful marker for metastatic cells.


Introducing surface-tethered poly(acrylic acid) brushes as 3D functional thin film for biosensing applications.
Carboxyl groups of surface-tethered poly(acrylic acid) (PAA) brushes should be able to serve as versatile moieties for a wide range of chemical modifications, including an attachment of bioactive species that can act as sensing probes for biosensors. In this research, poly(tert-butyl acrylate) (Pt-BA) brushes were prepared by surface-initiated atom transfer radical polymerization of tert-butyl acrylate. PAA brushes were then obtained after removal of the tert-butyl groups from the Pt-BA brushes by acid hydrolysis. The carboxyl group density of the PAA brushes can be varied as a function of chain length or molecular weight. The reactivity of the carboxyl groups of PAA brushes towards the immobilization of biotin, a frequently used model bioactive probe in biosensing applications, was evaluated. Qualitative determination of streptavidin (SA) binding to the biotin-attached PAA brushes was verified by fluorescence microscopy. The efficiency of the PAA brushes to act as a three dimensional (3D) precursor layer for biosensing applications was further demonstrated using surface plasmon resonance (SPR), where the biotin-attached PAA brushes showed an enhanced signal for the biospecific binding of SA in comparison with a self-assembled monolayer (SAM) of a carboxyl-terminated alkanethiol, used as a model two-dimensional (2D) conventional precursor layer. The PAA brushes showed very low non-specific interactions with two other tested proteins of a similar pI but different sizes. This desirable feature should be highly beneficial for the development of biosensors.


A Method for Microencapsulation of Cells and a Device for Its Realization.
The device for cell encapsulation makes it possible to fabricate microcapsules of a preset size with even smooth surface, without defects or adhesion to each other, with viable cells inside the capsule. The cells were derived from newborn piglet pancreases.


Sarcopenic obesity and post-operative morbidity after pancreatic surgery: a cohort study.
Several indices of sarcopenia (SARC) exist in the literature, however, there is no consensus as to the best SARC index to predict post-operative morbidity following pancreatic surgery. A prospectively collected database was reviewed in a single institution including a total of 89 consecutive patients who had undergone pancreatic resection between 2015 and 2018. A total of 89 patients comprised the cohort. Seventy-one percent (63/89) underwent pancreaticoduodenectomy. SARC was identified in 49 patients (55%) using psoas muscle index, 44 patients (49%) using the skeletal muscle index and 25 patients (28%) using the skeletal muscle attenuation. Post-operative morbidity did not differ between SARC and non-SARC (NSARC) patients using all three preoperative computed tomography measures (skeletal muscle index SARC 64%, 28/44, NSARC 64%, 29/45, P = 1.000; psoas muscle index SARC 63%, 31/49, NSARC 65%, 26/40, P = 0.810; skeletal muscle attenuation SARC 17/25, NSARC 40/64, P = 0.247). However, sarcopenic obesity was a significant independent risk factor for overall post-operative morbidity on multivariate analysis (odds ratio 1.241 (SE 0.608), P = 0.041) with the highest specificity (81%). Preoperative sarcopenic obesity can be an important independent predictor of post-operative morbidity following pancreatic resection. There remains a need for standardization of SARC indices.


Correlation between glucose metabolism parameters derived from FDG and tumor TNM stages and metastasis-associated proteins in colorectal carcinoma patients.
The aim of this study was to investigate the relationship between multiple metabolism parameters derived from FDG and tumor TNM stages as well as tumor metastasis-associated protein of GLUT-1 and MACC1 in colorectal carcinoma (CRC). Thirty-eight patients (24 males and 14 females) with primary CRC confirmed by elective surgery pathological, who also accepted 18F-FDG PET/CT scans during 2017 to 2019 were included in this study. The tumor classification of T, N and M is explained by the 7th American Joint Committee on Cancer (AJCC). 18F-FDG parameters of SUVmax, SUVmean, TLG and MTV were measured by drawing a region of interest on the primary lesions. The expression of GLUT-1 and MACC1 was quantified by immunohistochemical, and the correlation between metabolism parameters and tumor biomarkers were analyzed. According to our analysis, the 18F-FDG parameters of SUVmean was significantly correlated with tumor M status (P = 0.000) of primary CRC. The primary tumor lesion with higher SUVmax, TLG and MTV values prone to a high-T status (P = 0.002, 0.002 and 0.001, respectively). The high expression of GLUT-1/MACC1 weas more frequently involved with T3-4 stage and was poorly differentiated in CRC patients. Multivariate analysis found that the expression of GLUT-1 protein was correlated with SUVmax and MTV (R2 = 0.42, P = 0.013 and 0.004, respectively), moreover, the expression of MACC1 protein was correlated with TLG (R2 = 0.372, P = 0.000). Glucose metabolism parameters derived from FDG provides a noninvasive assessment of M status and T status in CRC patients. The expression of GLUT-1 and MACC1 was associated with 18F-FDG uptake in CRC patients.


A psychometric study of the prevalence of DSM-IV personality disorders among office-based methadone maintenance patients.
Using the DSM-IV criteria for personality disorders, prevalence rates for these disorders were evaluated among methadone maintenance patients, with a psychometric test--the Millon Clinical Multiaxial Inventory (MCMI-III). We found that 77% of patients met the study criteria for at least one personality disorder. Of those who had a personality disorder, 20% had two personality disorders, 14% had three personality disorders, and 6% had four personality disorders. Rates of specific personality disorders are reported. Consistencies and divergence from existing research literature are noted. It is suggested that future research compare psychometrically based self-report questionnaires to a structured clinical interview format, within the same clinical population.


The associations between sleep duration, cognitive function, and depressive symptoms: An analysis of Chinese adolescents from China Family Panel Studies.
The adverse impact of depressive symptoms on adolescents' physical and psychological health is becoming increasingly prominent. This study aims to examine the association between sleep duration, cognitive function, and depressive symptoms among Chinese adolescents. This study used data on a sample of 3724 adolescents collected from the China Family Panel Studies (CFPS). The multivariate logistic regression was conducted to estimate the association between sleep duration, cognitive function (measured by mathematics and vocabulary), and depressive symptoms among Chinese adolescents; the mediating effects of cognitive function were calculated by mediating model. The study found that approximately 6.49 % of Chinese adolescents had depressive symptoms, with an average CES-D8 score of 4.27 (SD: 3.11). Adolescents who reported a sleep duration of <6 h/night (OR = 2.34; 95 % CI = 1.30, 4.24) were at a higher risk of depressive symptoms, and the adolescents who had higher mathematics scores (>75 %) were more likely to be at a lower risk of depressive symptoms. Besides, the cognitive function competitively mediated the effect of sleep duration on depressive symptom (indirect effect = 0.043; 95 % CI = 0.023, 0.064). This is a cross-sectional study; all questions were self-reported; the sleep variable only included the sleep duration. Our study highlights that short sleep duration might increase the risk of depressive symptoms, and increasing cognitive function might reduce the occurrence of depressive symptoms in Chinese adolescents. The results displayed that sleep duration had a negatively direct effect on depressive symptoms, but the indirect effects of sleep duration on depressive symptoms via the cognitive function (i.e., mathematics and vocabulary tests) were significantly positive, indicating that the relationship between sleep duration and depressive symptoms was competitively mediated by cognitive function.


An assessment of the validity and reliability of the P022-P version of e-Celsius core temperature capsules.
Core temperature monitoring is a research tool used in many studies, though most popularly, heat strain. Ingestible core temperature capsules are a non-invasive and increasingly popular choice for measuring core body temperature, particularly considering the well-established validation of capsule systems. A newer version of the e-Celsius ingestible core temperature capsule has been released since the preceding validation study resulting in a paucity of validated research for the current version of capsules, P022-P, used by researchers. Using a 1:1 ratio of propylene glycol to water in a circulating water bath, and a reference thermometer with resolution and uncertainty of 0.01 °C, we assessed the validity and reliability of 24 P022-P e-Celsius capsules in three groups of eight, at seven temperature plateaus between 35 °C, and 42 °C in a test-retest format. The systematic bias of these capsules across all 3360 measurements was found to be -0.038 °C ± 0.086 °C (p < .001), The TEST-RETEST evaluation revealed excellent reliability by way of a minute overall mean difference of 0.0095 °C ± 0.048 °C (p < .001), and an intraclass correlation coefficient of 1.00 for each of TEST and RETEST conditions. Although quite small, differences in systematic bias across temperature plateaus were observed for both the OVERALL bias-between 0.00066 °C and 0.041°C-and TEST/RETEST bias-between 0.00010 °C and 0.016 °C. We found that the new capsule version outperforms manufacturer guarantees, with half of the systematic bias observed in a validation study of the previous capsule version. Though these capsules tend to slightly underestimate temperature, we find they possess excellent validity and reliability between 35 °C and 42 °C.


Studies on human T lymphocyte rosette formation with human and sheep erythrocytes.
A large proportion of normal human blood lymphocytes forms rosettes with neuraminidase-treated autologous and allogeneic human erythrocytes (nHRBC) or sheep red blood cells (SRBC). In contrast, the percentage of rosette-forming cells is extremely reduced in the peripheral blood of patients with chronic lymphocytic leukemia. The formation of mixed rosettes after addition of nHRBC and SRBC suggests that most normal rosette-forming lymphocytes have receptor sites for both types of erythrocytes. Rosette formation with neuraminidase-untreated HRBC occurs only with a small fraction of normal lymphocytes, but can be increased by preincubating the lymphocytes with neuraminidase. Similar to rosette formation with SRBC. the binding of nHRBC is temperature-dependent, is prevented by pretreatment of the lymphocytes with proteolytic enzymes, but is not inhibited by EDTA. Rosette dissociation during incubation at 37 degree C is accompanied by conversion of ring- or morula-like rosettes into horseshoes or caps.


Synthesis of Nanosheets Containing Uniformly Dispersed PdII Ions at an Aqueous/Aqueous Interface: Development of a Highly Active Nanosheet Catalyst for Mizoroki-Heck Reaction.
A method was developed to synthesize a nanosheet at the interface of an aqueous layer of PdII ions and an aqueous layer of hydrophilic polymer bearing a metal coordination unit (HPMC). The nanosheet was synthesized through generation of an interface by the addition of an aqueous solution of PdII ions with a low specific gravity (1.03 g/cm3) to a dispersed aqueous solution of HPMC with a high specific gravity (1.50 g/cm3), resulting in rapid cross-linking at the interface. An electron probe microanalysis mapping image showed that the PdII ions were uniformly dispersed in the nanosheet. The nanosheet showed a high catalyst activity for the Mizoroki-Heck cross-coupling reaction with a turnover number (TON) and turnover frequency (TOF) greater than 3,333,333 and 138,889 h-1, respectively. These are the greatest TON and TOF values reported for heterogeneous polymeric catalysts for the Mizoroki-Heck reaction.


Safety considerations in the epilepsy monitoring unit for psychogenic nonepileptic seizures.
Injury occurs in epilepsy monitoring units (EMUs) to patients with epileptic seizures (ES); however, there are limited data regarding the safety concerns of patients with psychogenic nonepileptic seizures (PNES) being monitored in EMUs. We reviewed EMU records from 116 PNES and compared them to 170 ES. Three falls (2.6%) occurred in PNES without injury compared to 6 falls (3.5%) in ES with 1 injury, a facial hematoma. Of the 9 total falls, 8 patients were ambulatory during their events. Several adverse incidents occurred for both groups. Of the PNES without staff response, 30 of 39 were due to PNES being less than 60s in duration, and 16 of 39 involved lack of push-button activation to alert the staff. For the ES group, 57 of 101 were due to electrographic seizures without seizure detection software or push-button activation. Similar safety protocols should be administered while monitoring these patients regardless of seizure type.


Warming up for a better fever: a randomized pilot study in pediatric oncology.
Fever in children is a major problem in pediatric oncology. Usual management leads to immediate antibiotic and antipyretic therapy, although there is consensus that antipyretic therapy should not be utilized with the sole aim of reducing body temperature. Increased body temperature during fever appears to be an effective modifier in terms of viral replication and enhanced host defense mechanisms against pathogens. Therefore, it might be beneficial to support febrile patients by applying gentle heat during the onset of fever to help the body to reach its new thermoregulatory set point. A randomized pilot study over 6 months will be conducted in a pediatric oncology department in an academic hospital in Germany. This study is a preparation for a multicenter clinical trial with two parallel groups concerning the efficacy of heat application vs. treatment as usual. One of the inclusion criteria is body temperatures ≥ 38.0 °C in n = 24 cases of patients receiving chemotherapy aged 18 months to 17 years. The first intervention consists of gentle heat application with hot water bottles at any sign of illness and onset of fever. The aim is to achieve a warm periphery equilibrated to trunk temperature of less than 0.5 °C. The second intervention is the avoidance of antipyretics. The control group receives the standard antipyretic treatment from the participating hospital. The purposes of this pilot study are proof of principle of intervention, evaluation of safety, feasibility, definition of endpoints, and to receive basic data for sample size calculation and needed resources. The main goal is to improve the care of children with cancer by providing the best possible support for febrile episodes. If fever support by heat reduces discomfort, administration of antipyretics and maybe even antibiotics, this would be an advancement in oncological fever management. This pilot study is intended to provide a basis for a main, multicenter, randomized trial and demonstrate the practicability of heat application in febrile patients in pediatric oncology. German Clinical Trials Register (DRKS), DRKS00028273 . Registered on 14 April 2022.