Accumulation of chemical elements in yellow-necked mice under a colony of great cormorants.
This study represents the first investigation into the accumulation of chemical elements in small mammals inhabiting the territory of a great cormorant colony. Trapping was done in the Juodkrantė great cormorant colony, one of the largest colonies in Europe. The accumulation of 20 chemical elements in the bodies (muscle and bones) of yellow-necked mice (Apodemus flavicollis) was investigated using the energy-dispersive x-ray fluorescence equipment Spectro Xepos HE. Two groups of positively inter-correlated chemical elements (Mg, Al, P, Ca and Al, S, Cl, K) were identified. The concentrations of five elements differed significantly between mice trapped in different zones of the colony with differing intensities of cormorant influence: the values of K and Cu in A. flavicollis increased in line with an increase in the influence of the cormorants, while the concentrations of Rb and Pb decreased. The concentrations of Mn differed between zones, but were not related to the intensity of bird influence. Differences in the concentration of Zn (ANOVA F = 24.38; p < 0.001), Fe (F = 4.60; p < 0.05) and Mo (F = 4.47; p < 0.05) were related to the gender factor, all concentrations being higher in females. The concentrations of Zn were age-dependent, being highest in adult individuals (21.7 ± 4.5 μg g-1) and exceeding those in subadult (19.4 ± 3.4 μg g-1) individuals or juveniles (16.7 ± 1.3 μg g-1). In general, the concentrations of accumulated elements in A. flavicollis from the territory of the cormorant colony were lower than in rodents from industrially polluted sites.


Analysis of Organ Utilization From Deceased Organ Donation in India.
This report presents an audit of utilization of various organs from deceased donors in different states of India over a 3-year period METHODS: Data released by the various regions on their official website was analyzed from 2015 to 2017.Regions with less than 25 donations per year were excluded while calculating utilization rates. Total organ donation in India had increased from 570 to 843 donations from 2015 to 2017 (47.8% increase) with southern states performing exceedingly well compared with northern states. Total organs retrieved during the 3-year period were 6659 with a 54.7% increase in organ retrieval in 2017 compared with 2015 (2592 vs 1675 respectively). The net utilization rate of kidneys was 87.35%. Total liver transplants done during this period were 1894. Net liver utilization rate was 86.81% over 3 years. Total Heart transplants during this period were 641 with net utilization rate of 28.98%. An increase in utilization rates was observed from 2015 to 2017 (19.33%-34.46%). A total of 217 lung transplants were done with net utilization rate of 8.86% with an increase in yearly utilization rate from 6.5% in 2015 to 11.97% in 2017. Total pancreas transplants remained low with 48 transplants over 3 year duration with net utilization rate of 2.25% but an increase in utilization rate was observed. (0.92% in 2015 to 2.1% in 2017). There is a significant regional variability in organ utilization in India. Evaluating and addressing the cause of high variability can further increase the transplant activity.


A new model of end-to-side nerve graft for multiple branch reconstruction: end-to-side cross-face nerve graft in rats.
The effectiveness of end-to-side nerve graft for multiple branch reconstruction was confirmed using a new rat four-branch facial nerve reconstruction model with end-to-side cross-face nerve graft. Forty Lewis rats were randomly divided into four groups with different reconstruction methods for four branches (bilateral buccal and marginal branches) of the bilateral facial nerves as follows: group I (n=12), single sciatic nerve graft with end-to-side neurorrhaphy; group II (n=12), four cable grafts using two sciatic and two ulnar nerves with end-to-end neurorrhaphy; group III (n=8), no repair; and group IV (n=8), sham operation. The four groups were compared with double retrograde tracing of the facial nucleus, electrophysiological and histomorphometrical assessment of the reconstructed facial nerve. Although there were no significant differences between groups I and II in the electrophysiological tests, group I showed more uniform and better reinnervation in the histomorphometrical assessment. Retrograde tracing of facial nucleus revealed significantly higher number of double-labeled neurons in group I although the total number of labeled neurons was not different between the two groups. End-to-side nerve graft shows a good functional recovery, requires less graft, and is easy to perform. With the availability of the side of the nerve graft itself as a nerve coaptation site, it can be an effective alternative in facial nerve reconstruction and be of great value in various kinds of peripheral nerve surgery.


Synthesis of a pyridine-based covalent organic framework as an efficient adsorbent for rhodamine B removal.
Covalent organic frameworks (COFs), featured with crystalline structures, permanent porosity, and designable organic skeletons, are good candidates for serving as adsorbents. Herein, a new pyridine-based two-dimensional COF (TAPP-DBTA-COF) was constructed via the condensation of 2,4,6-tris(4-aminophenyl)pyridine and 2,5-dibromobenzene-1,4-dicarbaldehyde. TAPP-DBTA-COF displayed high-performance for the removal of rhodamine B (Rh B) from water with high capacity, good adaptability and reusability. The maximum adsorption capacity for Rh B can reach up to 1254 mg g-1, and the kinetic constant was determined as k2 = 0.00244 g mg-1 min-1. Moreover, the corresponding amorphous polymer of TAPP-DBTA-COF, termed as TAPP-DBTA-COP, was synthesized from the same starting materials. The lower efficiency of TAPP-DBTA-COP in capture of Rh B revealed that the ordered pore structure, large specific surface area and rich adsorption sites play an important role in adsorption.


Guanidino compounds in serum and cerebrospinal fluid of non-dialyzed patients with renal insufficiency.
Twelve guanidino compounds were determined in simultaneously sampled serum and cerebrospinal fluid of eight non-dialyzed patients with renal insufficiency. Liquid cation exchange chromatography with a highly sensitive fluorescence detection method was used. In patients with serum urea levels about 10 times higher than in controls, the levels of guanidinosuccinic acid, creatinine, guanidine and methylguanidine, in serum as well as in cerebrospinal fluid, are at least 10 times higher than in control subjects. The levels of argininic acid and N-alpha-acetylarginine (in serum) and gamma-guanidinobutyric acid (in cerebrospinal fluid) are slightly increased (less than 10 X). The levels of the other guanidino compounds are close to normal values. A significant positive correlation exists between the guanidinosuccinic acid, creatinine and guanidine levels in serum and cerebrospinal fluid. The accumulation of several experimentally proven toxic guanidino compounds could contribute to the complex nervous system symptomatology and the hematological complications seen in renal insufficiency.


Clinicopathological features of tumors as predictors of the efficacy of primary neoadjuvant chemotherapy for operable breast cancer.
Neoadjuvant chemotherapy (NC) is standard therapy for patients with locally advanced breast cancer and is increasingly used for early-stage operable disease. Clinical and pathological responses are important prognostic parameters for NC, which aims to achieve a pathological complete response or tumor reduction to reduce the volume of subsequent breast resection. Clinicopathological markers that predict patient response to NC are needed to individualize treatment. From 1998 to 2006, 368 patients with primary breast cancer underwent curative surgical treatment after NC (anthracycline and/or taxane without trastuzumab). We retrospectively evaluated the clinicopathological features and classification of the tumors using computed tomography (CT) before NC and analyzed the correlation with the pathological complete response (pCR) and reduction of tumor size after treatment. The overall response and pCR rates in these patients were 86% and 17%, respectively. In multivariate analysis, classification as a scirrhous-type tumor was an independent predictor of reduced likelihood of pCR (p=0.0115; odds ratio 0.21). For tumor reduction, histological grade 3 (p=0.0002; odds ratio 3.3) and localized tumors identified by using CT imaging (p=0.0126; odds ratio 2.4) were independent predictors in multivariate analysis. In this study, NC often did not result in pCR for breast cancers classified as scirrhous. Furthermore, tumor type classification using CT imaging and histological grading was effective to predict tumor reduction in response to NC that included an anthracycline and/or a taxane.


Evolution of dissolved organic nitrogen (DON) during sludge reject water treatment revealed by FTICR-MS.
This study evaluated the ability to remove dissolved organic matter (DOM), particularly dissolved organic nitrogen (DON), at a molecular level using Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) in a full-scale reject water treatment project comprising three steps of short-cut nitrification and denitrification, two-stage AO, and ultrafiltration membrane system. The results indicated that short-cut nitrification and denitrification were effective in reducing the DON concentration from an average of about 180 mg/L to 43 mg/L. The average molecular weight of DOM showed a decreasing trend from 238 Da to 160 Da. The percentage of nitrogen-containing organic compounds (CHON-DOM), which is the primary component of reject water DOM, increased from 65.79 % to 72.35 %, while the percentage of CHO-DOM decreased from 20.67 % to 15.24 %. The percentage of CHOS-DOM remained stable at 12.21 %-13.54 %. The percentage of protein-DOM decreased from 50.32 % to 18.40 %, while lignin-DOM increased from 36.16 % to 55.88 % and carbohydrate-DOM increased from 2.68 % to 9.74 %. The short-cut nitrification and denitrification and ultrafiltration membrane system both generated more unsaturated, highly aromatic DOM. This study provides insights into the effects of different wastewater treatment processes on the evolution of DOM/DON, which can be useful for effective DON control.


Complement system in sodium taurocholate pancreatitis in the rat.
The role of the complement system was studied in Na-taurocholate pancreatitis in rats. Complement activity (CH 50) was determined at various times in the course of pancreatitis. Immediately after induction of acute pancreatitis, serum complement activity declined and massive C 3 deposits could be detected in the vicinity of acinar necroses and necrobioses. After a phase of recovery three to six hours postoperatively a second complement consumption occurred. Lethality rate increased as serum complement activity fell below 50% of preoperative values. The degree of C 3 deposition increased up to six hours. Decline of serum complement activity and deposition within the pancreas seemed to be correlated with histologically demonstrable tissue lesion. The first decline of complement activity in serum is thought to be caused by liberation of complement activating substances within the pancreas due to the detergent action of Na-taurocholate itself. The second decline, however, may be due to the liberation of complement activating and/or destroying enzymes into the blood stream.


Impact of Variant Histology on Occult Nodal Metastasis after Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: A Review of the National Cancer Database.
Up to 14% of bladder urothelial carcinoma has variant histology (VH), which is associated with a higher incidence of occult regional lymph node metastasis. Neoadjuvant chemotherapy (NAC) is the gold-standard for resectable cT2-4 disease as it achieves pathologic complete response (pCR) in select patients at the time of radical cystectomy (RC). A landmark trial demonstrated chemosensitivity and pT0 status in the setting of VH. pT0N+ pathology in patients undergoing subsequent RC has prompted concerns about post-chemotherapy bladder preservation. We investigate how VH impacts pathologic primary site and nodal downstaging post-NAC. We queried the National Cancer Database for cT2-4N0M0 patients who underwent NAC and RC between 2004 and 2016. These patients were stratified into pure urothelial cell carcinoma (UCC) and VH. The rate of downstaging to ≤pT1 was analyzed, along with pN+ status. Overall survival was analyzed using the Kaplan-Meier method and multivariable Cox proportional hazards regression model. Multivariable models were adjusted for demographic and clinicopathologic variables. Of 5,335 patients, 92.1% were UCC and 7.9% VH. UCC was associated with better unadjusted survival and lower adjusted odds of being pN+ (aOR = 0.60, P < .001). Squamous cell, glandular, and sarcomatoid histologies were significantly associated with decreased adjusted odds of any pT downstage. Neuroendocrine histology (NE) trended towards increased adjusted odds of downstage to pT0N0. Patients with VH were more likely to harbor occult regional lymph node metastasis in the setting of intravesical pCR. NE had the highest pT0N0 rate, with potential implications on post-NAC bladder preservation. These findings reinforce the role of RC after NAC especially for VH.


Daily melatonin injections have only minor effects on gonadotropins of intact or castrated male rats kept under constant or periodic light.
Intact and castrated adult male Wistar rats were kept under constant or periodic (lights on 0600 and off 1800 h) light for 1 wk. During the study they received melatonin or saline injections daily either at 0900 or 1600 h. After each experiment, serum samples and the adenohypophyses were collected between 1000 and 1100 h and the gonadotropin concentrations were measured radioimmunologically. We had previously found changes in light sensitivity of the hypothalamo-pituitary axis of castrated rats and hypothesized that this axis could also involve changes in sensitivity to exogenous melatonin. However, the results of the present study do not support the hypothesis.


A Switch in the Dynamics of Intra-Platelet VEGF-A from Cancer to the Later Phase of Liver Regeneration after Partial Hepatectomy in Humans.
Liver regeneration (LR) involves an early inductive phase characterized by the proliferation of hepatocytes, and a delayed angiogenic phase distinguished by the expansion of non-parenchymal compartment. The interest in understanding the mechanism of LR has lately shifted from the proliferation and growth of parenchymal cells to vascular remodeling during LR. Angiogenesis accompanied by LR exerts a pivotal role to accomplish the process. Vascular endothelial growth factor (VEGF) has been elucidated as the most dynamic regulator of angiogenesis. From this perspective, platelet derived/Intra-platelet (IP) VEGF-A should be associated with LR. Thirty-seven patients diagnosed with hepatocellular carcinoma and undergoing partial hepatectomy (PH) were enrolled in the study. Serum and IP VEGF-A was monitored preoperatively and at four weeks of PH. Liver volumetry was determined on computer models derived from computed tomography (CT) scan. Serum and IP VEGF-A was significantly elevated at four weeks of PH. Preoperative IP VEGF-A was higher in patients with advanced cancer and vascular invasion. Postoperative IP VEGF-A was higher after major liver resection. There was a statistically significant correlation between postoperative IP VEGF-A and the future remnant liver volume. Moreover, the soluble vascular endothelial growth factor receptor-1 (sVEGFR1) was distinctly down-regulated suggesting a fine-tuned angiogenesis at the later phase of LR. IP VEGF-A is overexpressed during later phase of LR suggesting its implications in inducing angiogenesis during LR.


Optic nerve involvement in retinoblastoma.
This retrospective review of 814 retinoblastoma patients discloses 240 cases of tumor extension into the optic nerve. Optic nerve involvement was classified according to the degree of invasion; grade I is superficial invasion of the optic nerve head only, grade II is involvement up to and including the lamina cribrosa, grade III is involvement beyond the lamina cribrosa, and grade IV is involvement up to and including the surgical margin. The incidence of optic nerve involvement was 29.5% (240/814). The mortality rate of patients with optic nerve involvement with grade I was 10%; grade II, 29%; grade III, 42%; and grade IV, 78%. Actuarial life-table analysis shows an increased mortality rate with increasing grade of optic nerve involvement. Multivariate statistical analysis shows that the grade of optic nerve involvement and the age at diagnosis of optic nerve involvement are the factors most significantly associated with survival.


A20 is dynamically regulated in the heart and inhibits the hypertrophic response.
Nuclear factor (NF)-kappaB signaling has been implicated in cardiomyocyte hypertrophy. Here, we determine the cardiac regulation and biological activity of A20, an inhibitor of NF-kappaB signaling. Mice were subjected to aortic banding, and A20 expression was examined. A20 mRNA upregulation (4.3+/-1.5-fold; P<0.05) was detected 3 hours after banding, coinciding with peak NF-kappaB activation. A20 was also upregulated in cultured neonatal cardiomyocytes stimulated with phenylephrine or endothelin-1 (2.8+/-0.6- and 4+/-1.1-fold, respectively; P<0.05), again paralleling NF-kappaB activation. Infection of cardiomyocytes with an adenoviral vector (Ad) encoding A20 inhibited tumor necrosis factor-alpha-stimulated NF-kappaB signaling with an efficacy comparable to dominant negative inhibitor of kappa-B kinase beta (dnIKKbeta). Ad.dnIKKbeta-infected cardiomyocytes exhibited increased apoptosis when they were serum starved or subjected to hypoxia-reoxygenation, whereas Ad.A20-infected cardiomyocytes did not. Expression of Ad.A20 inhibited the hypertrophic response in cardiomyocytes stimulated with phenylephrine or endothelin-1. A20 is dynamically regulated during acute biomechanical stress in the heart and functions to attenuate cardiac hypertrophy through the inhibition of NF-kappaB signaling without sensitizing cardiomyocytes to apoptotic cell death.


Comparison of early cardiovascular risk among Brazilian and African university students.
Cardiovascular diseases are among the main causes of mortality worldwide, and dyslipidemia is a principal factor risk. Hence the study of biochemical markers is necessary for early diagnosis. Evaluate biomarkers to diagnose the risks of cardiovascular diseases in healthy Brazilian and African young adults. Weight, height, waist circumference, percentage of body fat and systemic blood pressure were measured; and fasting blood samples were taken for biochemical analysis. Triglycerides, total cholesterol, HDL-c, and apolipoproteins A-I and B were measured on automated equipment using commercially available kits, in addition to the tests of antioxidant capacity of HDL and the enzymatic activity of Paraoxonase 1. After statistical analysis, it was found that BMI, WC, fat (%), triglycerides, ApoB/ApoA-I ratio and Vmax were higher in Brazilians, while HDL-c, ApoA-I, Lag Time, Vmax and PON1 activity were higher in Africans. In Brazilians, the ApoB/ApoA-I ratio was related to obesity factors and lipid profile, but in Africans it was related only to lipids. The antioxidant capacity of HDL and PON1 activity was better in Africans. Through independence testing, we observed an association with moderate risk of myocardial infarction with gender in Africans. In the binary logistic regression analysis, it was found that men in general - and particularly African men - have higher risk of myocardial infarction than women; Odds Ratio 2144 (CI95%: 1343-3424) and 2281 (CI95%: 1082-4811), respectively. The anthropometric and biochemical parameters of Brazilians, especially men, predispose them to greater risks of cardiovascular diseases.


A new approach to postvasectomy semen analyses eliminates the need to evaluate a fresh specimen.
According to current guidelines, confirmation that vasectomy results in sterility depends on microscopic examination of postvasectomy semen for the presence of spermatozoa. Guidelines established in 2012 require examination of a fresh specimen within 2 h of collection, which necessitates the patient making an appointment with either the surgeon's office or a licensed clinical laboratory. Twenty-five to 42% of patients fail to comply with postvasectomy semen analysis (PVSA). To determine if an at-home semen collection kit can substitute for the evaluation of a fresh specimen and improve patient compliance with postvasectomy spermatozoa assessment. The kit contains a patented aldehyde-fixative that maintains spermatozoa and semen cells in suspension for quantitation. Patients order a PVSA kit to be delivered to their home and can collect a semen specimen and return it to the laboratory through regular US mail. From January 2011 through December 2018, 6096 men undergoing vasectomy by 184 urologists in 33 states in the US ordered PVSA kits, of which 5408 (89%) returned at least one for analysis. Of those, 398 men (7.4%) returned the first kit with greater than 10,000 spermatozoa/ml within a year of vasectomy, of which only 4.4% contained greater than 100,000 spermatozoa/ml 12 weeks postsurgery. This suggests that fewer than 5% of postvasectomy patients might need follow-up fresh semen analyses, greatly easing the logistical burden of PVSA. Ninety percent of surgeons returning a patient satisfaction questionnaire said their patients "never" complained about using PVSA kits. These data support the adoption of a new standard for PVSA that does not involve an initial evaluation of a fresh semen specimen.


"Stress Control" as a Large Group Psychoeducational Intervention at Step 2 of IAPT Services: Acceptability of the Approach and Moderators of Effectiveness.
"Stress Control" (SC) has been adopted as a core intervention in step 2 of Improving Access to Psychological Therapies (IAPT) services, but contemporary evidence of effectiveness has lagged behind service uptake. To investigate the acceptability and effectiveness of SC and to explore moderators of outcome. Analysis of acceptability (via attendance rates) and effectiveness (via IAPT minimum dataset). SC was well tolerated with 73.3% of all patients and 75.4% of "clinical cases" attending three or more sessions. Of the 546 "clinical cases" attending SC and not in receipt of other interventions, 37% moved to recovery. Attendance improved outcome; for those patients attending all SC sessions the recovery rate rose to 59.2%. SC appears a well-tolerated and effective intervention that enables large numbers to gain access to treatment in an organizationally efficient manner. Attendance is important in facilitating SC outcomes and research evaluating attendance interventions are needed.


Effects of calcium concentration on nonviral gene delivery to bone marrow-derived stem cells.
Calcium ions (Ca2+ ) influence natural bone healing, and calcium is frequently used in bone tissue engineering scaffolds and cements. Scaffolds can also incorporate gene delivery systems to further promote osteoblast differentiation. Thus, our goal was to identify if Ca2+ concentration affects the transfection of bone marrow stromal cells because these cells play a major role in bone healing and can infiltrate gene-activated scaffolds designed to promote bone growth. Bone marrow-derived mesenchymal stem cells (BMSCs) were cultured in media with Ca2+ concentrations ranging from 0 to 20 mM and transfected with polyethyleneimine-plasmid DNA (PEI-pDNA) complexes. Cell viability and transfection efficiency were determined using MTS assays and flow cytometry, respectively. PEI-pDNA complex localization in BMSCs was assessed using fluorescence microscopy. To determine BMSC differentiation, messenger RNA (mRNA) for osteocalcin and CBFA1 was quantified using real time-polymerase chain reaction (PCR). Calcium deposition was qualitatively assessed after three and 14 days using Alizarin Red staining. Our results indicate that Ca2+ levels between 8 and 12 mM positively impacted transfection of BMSCs with PEI-pDNA complexes in terms of cell viability and transfection efficiency. A Ca2+ concentration of 10 mM also increased the expression of an osteogenic gene, osteocalcin, when the cells were transfected with plasmid DNA encoding bone morphogenetic protein 2 (BMP-2). Ca2+ at a 10 mM concentration can significantly reduce toxicity and enhance transfection efficiency when combined with PEI-pDNA complexes, and this combination can be specifically applied to further enhance the differentiation of BMSCs by using the combination of polyethyleneimine-plasmid bone morphogenetic protein 2 (PEI-pBMP-2) and 10 mM Ca2+ as compared with PEI-pBMP-2 alone.


A 1:1 ratio of cannabidiol: tetrahydrocannabinol attenuates methamphetamine conditioned place preference in mice: A prospective study of antidopaminergic mechanism.
A 1:1 ratio of cannabidiol to tetrahydrocannabinol (CT) was suggested to be safer for therapeutic purposes in many illnesses. However, CT effects on methamphetamine (METH) conditioned place preference (CPP) remained largely unexplored. This study aimed to examine the effects of CT on METH CPP mice evaluated by animal behaviors accompanied by local field potential (LFP) signals analysis. Male ICR mice were implanted with the LFP electrode in the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Animals were next subjected to induce METH CPP by peritoneal injection with 1 mg/kg METH and 0.9 % NaCl on an alternate day for ten sessions and confined to the corresponding compartment for 30 min meanwhile control mice were given normal saline all day for both compartments. On testing day, either 10 mg/kg CT or 20 mg/kg bupropion (BP), a dopamine reuptake inhibitor, and VTA GABAergic suppressor were orally administered before CPP testing. The results revealed that CPP scores elevation was observed in the METH+vehicle and METH+BP mice, but this was reversed by CT treatment. Although both METH+vehicle and METH+BP enhanced the VTA delta power, NAc gamma I power, NAc delta-gamma coupling, and VTA-NAc gamma I coherence, changes in opposite trends of all mentioned parameters were seen by CT application. These improvements were postulated to involve the antidopaminergic effects of CT via modulations of neural signaling in the VTA and NAc. Altogether, the evidence-based study may suggest the use of CT as alternative drug for METH-seeking and craving therapy.


Mass spectra of copolymers which display compositional drifts or sequence constraints.
The spectral features appearing in mass spectra of random and block copolymers which display a drift in composition are discussed along with features appearing in mass spectra of terpolymers and tetrapolymers with sequence constraints. It is shown that previous models cannot account for these features. A new model is presented and a compact equation is derived which yields MS intensities. The prediction of the model is compared with some literature data, namely mass spectrometric data concerning a block copolymer sample containing units of alpha-methyl styrene and of methylmethacrylate which display a strong drift in composition, the molar fraction of methylmethacrylate units changing from 0.99 to 0.80 when passing from short to long macromolecular chains. The agreement between theory and experiment is good. A hyperbranched polymer obtained by condensing 4,4'-bis[p(acetoxy)phenyl] valeric acid (referred to as diphenolic acid, DPA) was then considered. The polymer turned out to be a copolymer with regular DPA units and modified DPA units (possessing a phenol group). The molar fraction of regular DPA units changes from 0.80 to 0.95 when passing from low masses to high masses. Copolymers with sequence constraints are considered, such as ABC copolymers in which AA cannot be found along the chain or ABCD copolymers in which A cannot follow A, B cannot follow B, etc. The novel method is applied to an exactly alternating copolymer with units of styrene (St) and maleic anhydride (MAH). The St-MAH sample turned out to be a complex mixture and the presence of a small amount of units of maleic acid (MAC) is detected. The abundance of MAC, estimated by the chain statistical method, is 5%. The method is applied to the copolymer obtained by reactive blending of poly(butylene terephthalate) and poly(bisphenolA carbonate). In this case, the theoretical spectra are generated and spectral features are discussed.


Burden and predictors of statin use in primary and secondary prevention of atherosclerotic vascular disease in the US: from the National Health and Nutrition Examination Survey 2017-2020.
To assess the current state of statin use, factors associated with non-use, and estimate the burden of potentially preventable atherosclerotic cardiovascular diseases (ASCVD) events. Using nationally representative data from the 2017 to 2020 National Health and Nutrition Examination Survey, statin use was assessed in primary prevention groups: high ASCVD risk ≥ 20%, LDL-cholesterol (LDL-C) ≥ 190 mg/dL, diabetes aged 40-75 years, intermediate ASCVD risk (7.5 to <20%) with ≥1 ASCVD risk enhancer and secondary prevention group: established ASCVD. Atherosclerotic cardiovascular disease risk was estimated using pooled cohort equations. We estimated 70 million eligible individuals (2.3 million with LDL-C ≥ 190 mg/dL; 9.4 million with ASCVD ≥ 20%; 15 million with diabetes and age 40-75years; 20 million with intermediate ASCVD risk and ≥1 risk enhancers; and 24.6 million with established ASCVD), about 30 million were on statin therapy. The proportion of individuals not on statin therapy was highest in the isolated LDL-C ≥ 190 mg/dL group (92.8%) and those with intermediate ASCVD risk plus enhancers (74.6%) followed by 59.4% with high ASCVD risk, 54.8% with diabetes, and 41.5% of those with established ASCVD groups. Increasing age and those with health insurance were more likely to be on statin therapy in both the primary and secondary prevention categories. Individuals without a routine place of care were less likely to be on statin therapy. A total of 385 000 (high-intensity statin) and 647 000 (moderate-intensity statin) ASCVD events could be prevented if all statin-eligible individuals were treated (and adherent) for primary prevention over a 10-year period. Statin use for primary and secondary prevention of ASCVD remains suboptimal. Bridging the therapeutic gap can prevent ∼1 million ASCVD events over the subsequent 10 years for the primary prevention group. Social determinants of health such as access to care and healthcare coverage were associated with less statin treatment. Novel interventions to improve statin prescription and adherence are needed.


Saving Contrast Media in Coronary CT Angiography with Photon-Counting Detector CT.
To determine the optimal virtual monoenergetic image (VMI) energy level and the potential of contrast-media (CM) reduction for coronary computed tomography angiography (CCTA) with photon-counting detector CT (PCD-CT). In this institutional review board-approved study, patients who underwent CCTA with dual-source PCD-CT with an identical scan protocol and radiation dose were included. In group 1, CCTA was performed with our standard CM protocol (volume: 72-85.2 mL, 370 mg iodine/mL). VMIs were reconstructed from 40 to 60 keV at 5 keV increments. Objective image quality (IQ) (vascular attenuation, image noise, and contrast-to-noise ratio [CNR]) was measured. Two blinded, independent readers rated subjective IQ (overall IQ, subjective image contrast, and subjective noise using a five-point discrete visual scale). Results of group 1 served to determine the best VMI level for CCTA. In group 2, CM volume was reduced by 20%, and in group 3 by another 20%. A total of 100 patients were enrolled (45 females, mean age 54 ± 13 years). Inter-reader agreement was good-to-excellent for all comparisons (κ > 0.6). In group 1, the best VMI level regarding objective and subjective IQ was 45 keV, which was selected as the reference for groups 2 and 3. For group 2, mean vascular attenuation was 890 Hounsfield units (HU) and mean CNR was 26, with no differences compared to group 1, 45 keV for both objective and subjective IQ. For group 3, mean vascular attenuation was 676 HU and mean CNR was 21, and all patients were rated as diagnostic except one (severe motion artifacts). Increased IQ of PCD-CT can be used for considerable CM volume reduction while still maintaining a diagnostic IQ of CCTA.


Randomized phase II adjuvant trial to compare two treatment durations of icotinib (2 years versus 1 year) for stage II-IIIA EGFR-positive lung adenocarcinoma patients (ICOMPARE study).
Despite the prolonged median disease-free survival (DFS) by adjuvant targeted therapy in non-small-cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations, the relationship between the treatment duration and the survival benefits in patients remains unknown. In this multicenter, randomized, open-label, phase II trial, eligible patients aged 18-75 years with EGFR-mutant, stage II-IIIA lung adenocarcinoma and who had not received adjuvant chemotherapy after complete tumor resection were enrolled from eight centers in China. Patients were randomly assigned (1 : 1) to receive either 1-year or 2-year icotinib (125 mg thrice daily). The primary endpoint was DFS assessed by investigator. The secondary endpoints were overall survival (OS) and safety. This study was registered at ClinicalTrials.gov (NCT01929200). Between September 2013 and October 2018, 109 patients were enrolled (1-year group, n = 55; 2-year group, n = 54). Median DFS was 48.9 months [95% confidence interval (CI) 33.1-70.1 months] in the 2-year group and 32.9 months (95% CI 26.6-44.8 months) in the 1-year group [hazard ratio (HR) 0.51; 95% CI 0.28-0.94; P = 0.0290]. Median OS for patients was 75.8 months [95% CI 64.4 months-not evaluable (NE)] in the 2-year group and NE (95% CI 66.3 months-NE) in the 1-year group (HR 0.34; 95% CI 0.13-0.95; P = 0.0317). Treatment-related adverse events (TRAEs) were observed in 41 of 55 (75%) patients in the 1-year group and in 36 of 54 (67%) patients in the 2-year group. Grade 3-4 TRAEs occurred in 4 of 55 (7%) patients in the 1-year group and in 3 of 54 (6%) patients in the 2-year group. No treatment-related deaths or interstitial lung disease was reported. Two-year adjuvant icotinib was shown to significantly improve DFS and provide an OS benefit in EGFR-mutant, stage II-IIIA lung adenocarcinoma patients compared with 1-year treatment in this exploratory phase II study.


Deep-learning-based automatic evaluation of rice seed germination rate.
Rice is an important food crop plant in the world and is also a model plant for genetics and breeding research. The germination rate is an important indicator that measures the performance of rice seeds. Currently, solutions involving image processing techniques have substantial challenges in the identification of seed germination. The detection of rice seed germination without human intervention involves challenges because the rice seeds are small and densely distributed. In this article, we develop a convolutional neural network (YOLO-r) that can detect the germination status of rice seeds and automatically evaluate the total number of germinations. Image partition, the Transformer encoder, a small target detection layer, and CDIoU loss are exploited in YOLO-r to improve the detection accuracy. A total of 21 429 seeds were collected, which have different phenotypic characteristics in length, shape, and color. The results show that the mean average precision of YOLO-r is 0.9539, which is higher than the compared models. Moreover, the average detection time per image of YOLO-r was 0.011 s, which meets the real-time requirements. The experimental results demonstrate that YOLO-r is robust to complex situations such as water stains, impurities, awns, adhesion, and so on. The results also show that the mean absolute error of the predicted germination rate mainly exists within 0.1. Numerous experimental studies have demonstrated that YOLO-r can predict rice germination rate in a fast, easy, and accurate manner. © 2022 Society of Chemical Industry.


Three-dimensional cone beam computed tomography definition of the anatomical subregions of the upper airway: a validation study.
The exact boundaries of the upper airway subregions remain undefined. Consequently, anatomical limits vary greatly among different research groups and impede unbiased comparisons. The aim of this study was to provide clinical three-dimensional anatomical limits for the upper airway subregions, translate them into accurate and reliable cephalometric landmarks in cone beam computed tomography (CBCT) data, and validate the proposed measuring protocol. The upper airway of 40 normative individuals aged 23-35 years was evaluated with Dolphin Imaging(®) software. An appropriate grey-scale threshold value was pre-calculated. After adapting specific head positioning and virtual orientation protocols, the volume and minimum cross-sectional area of the nasopharynx, oropharynx, and hypopharynx, as previously defined by the authors, were calculated. Intra- and inter-observer reliability was excellent for volumes and moderate for areas. The sexual dimorphism analysis revealed a significantly greater oropharyngeal volume, hypopharyngeal volume, and minimum cross-sectional oropharyngeal area in males than in females. In conclusion, the proposed subregion definition showed technical feasibility and statistical reliability, especially for three-dimensional calculations. The reliability of two-dimensional calculations may be increased with improved head positioning during CBCT scanning and subsequent virtual head orientation. Standardization of the proposed anatomical limits has the potential to homogenize upper airway subregion analysis and permit comparisons among future studies.


Incorporating the Molecular Mimicry of Environmental Antigens into the Causality of Autoimmune Hepatitis.
Molecular mimicry between foreign and self-antigens has been implicated as a cause of autoimmune hepatitis in experimental models and cross-reacting antibodies in patients. This review describes the experimental and clinical evidence for molecular mimicry as a cause of autoimmune hepatitis, indicates the limitations and uncertainties of this premise, and encourages investigations that assess diverse environmental antigens as sources of disease-relevant molecular mimics. Pertinent articles were identified in PubMed using multiple search phrases. Several pathogens have linear or conformational epitopes that mimic the self-antigens of autoimmune hepatitis. The occurrence of an acute immune-mediated hepatitis after vaccination for severe acute respiratory syndrome (SARS)-associated coronavirus 2 (SARS-CoV-2) has suggested that vaccine-induced peptides may mimic disease-relevant tissue antigens. The intestinal microbiome is an under-evaluated source of gut-derived antigens that could also engage in molecular mimicry. Chaperone molecules may enhance the pathogenicity of molecular mimics, and they warrant investigation. Molecular mimics of immune dominant epitopes within cytochrome P450 IID6, the autoantigen most closely associated with autoimmune hepatitis, should be sought in diverse environmental antigens and assessed for pathogenicity. Avoidance strategies, dietary adjustments, vaccine improvement, and targeted manipulation of the intestinal microbiota may emerge as therapeutic possibilities. In conclusion, molecular mimicry may be a missing causality of autoimmune hepatitis. Molecular mimics of key immune dominant epitopes of disease-specific antigens must be sought in diverse environmental antigens. The ubiquity of molecular mimicry compels rigorous assessments of peptide mimics for immunogenicity and pathogenicity in experimental models. Molecular mimicry may complement epigenetic modifications as causative mechanisms of autoimmune hepatitis.


Recovery from staphylococcal septicaemia in neutropenic patients without removal of the previously inserted central venous catheter.
An open clinical study was conducted in the haematological department of an intensive care unit to investigate cure of staphylococcal septicaemia in neutropenic central venous catheter carriers without removal of the line. Thirteen neutropenic patients with a central venous catheter were investigated. These patients were under treatment for haematological malignancies and had at least 2 blood cultures positive for Staphylococcus aureus or coagulase-negative staphylococcus. Antibiotherapy including vancomycin was given through the catheter. Each case was re-evaluated on day 3 of treatment. The catheter was removed if blood cultures remained positive or if clinical signs of bloodstream infection persisted or worsened. Clinical recovery was obtained in ten patients and bacterial eradication in twelve. Three patients died from septic shock: two deaths were not related to staphylococcal septicaemia; one death was due to a staphylococcal septic shock which occurred within a few hours of admission, despite of prompt removal of the central venous catheter. With appropriate antibiotherapy, leaving the central venous catheter in place would appear possible in cases of staphylococcal septicaemia. Response to treatment, however, must be carefully monitored.


Environmental prevalence, fate, impacts, and mitigation of microplastics-a critical review on present understanding and future research scope.
Microplastics are considered to be ubiquitous and widespread emerging contaminants. They are persistent in the nature and pose considerable harm to the environment. Their omnipresence is documented in almost all aquatic habitats, several atmospheric and terrestrial environments, and also in human consumables. The objective of this review is to provide an overview of the environmental prevalence of the microplastics in all environmental compartments, and their possible adverse impacts. It also presents review of the studies conducted in India and the epitome of potential mitigation measures. The need and direction of future research are highlighted. The review will help in determining the exposure levels, environmental consequences, and risk estimations, and will guide the researchers and policymakers.


Raf-1 is not a major upstream regulator of MAP kinases in rat fibroblasts.
RCR cells are NRK clones in which Raf-1 production is blocked by the expression of an antisense RNA, and consequently they are refractory to transformation by various oncogenes. In RCR cells, MAP kinases (ERK1 and ERK2) were activated to an extent and in a time course similar to those of the original NRK cells, irrespective of whether the stimulus was oncogenic or non-oncogenic. Moreover, there was no significant elevation of ERK activities in oncogene-transformed NRK cells. These results indicate that Raf-1 kinase is not the major upstream activator of ERK's in NRK cells and that neither ERK1 nor ERK2 are likely to mediate oncogenic signals from Raf-1 kinase.


High-level expression of human interleukin-17 in the yeast Pichia pastoris.
Human interleukin-17 (hIL-17) gene without the signal sequence was isolated from activated peripheral blood lymphocytes by RT-PCR, then highly expressed in the yeast Pichia pastoris in the form of the glycosylated monomer. The monomer of rhIL-17 stimulated mouse fibroblast 3T3 cells to secrete IL-6 and was specifically bound to its receptors on 3T3 cells.


A case of multiple lung carcinoid tumors localized in the right lower lobe.
Typical pulmonary carcinoid (TC) tumors are low-grade neuroendocrine tumors and usually detected as indolent solitary tumors. We herein report a case of multiple pulmonary carcinoid tumors and tumorlets localized in the right lower lobe with no underlying lung disorders suggesting diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). A 28-year-old man with multiple 1-to-8-mm pulmonary nodules in the peripheral pulmonary parenchyma of the right lower lobe was referred to our hospital. The patient underwent a surgical biopsy. Pathological examination revealed multiple nodules composed of spindle cells, and immunohistochemistry revealed staining for chromogranin A, synaptophysin, and CD56, suggesting neuroendocrine tumors. He was diagnosed as having multiple TC tumors and tumorlets. Neuroendocrine cell hyperplasia (NECH) was also observed on some bronchioles. A follow-up CT scan after 6 months showed no changes in the sizes of the nodules and no new lesions. The present case was histopathologically compatible with DIPNECH but it occurs mainly in elderly women. The patient might be in an early stage of DIPNECH before progression to symptomatic DIPNECH. In conclusion, clinicians should consider the possibility of carcinoid tumors and tumorlets in cases with multiple pulmonary nodules even if they are localized in one lobe.


A low dimensional dynamical model of the initial pulmonary innate response to infection.
In order to gain a deeper understanding of the onset and progression of pulmonary infections we present and analyze a low dimensional, phenomenological model of infection and the innate immune response in the lungs. Because pulmonary innate immunity has features unique to itself, general mathematical models of the immune system may not be appropriate. The differential equations model that we propose is based on current knowledge of the biology of pulmonary innate immunity and accurately reproduces known features of the initial phase of the dynamics of pulmonary innate system as exhibited in recent experiments. Further, we propose to use the model as a starting point for interrogation with clinical data from a new noninvasive technique for sampling alveolar lining fluid.


Relationship between masking levels and phonatory stability in normal-speaking women.
Disruption of auditory feedback such as masking has been shown to influence vocal production. A reliable finding is an increase in intensity level; an increase in fundamental frequency (F0) is a less robust finding. Research is lacking concerning the effects of auditory masking on measures of phonatory stability such as jitter and harmonics-to-noise ratio (HNR). This study investigated changes in intensity, F0, jitter, and HNR in 22 normally speaking college aged women. Subjects produced the vowel /a/ under three conditions: no masking level (0-dB ML), 50-dB ML, and 80-dB ML. Significant differences between conditions emerged for intensity; means for the other measures were not significantly different. Intraindividual differences between conditions for each variable are discussed in the framework of auditory versus kinesthetic feedback.


Introduction of information during the initial medical visit: consequences for patient follow-through with physician recommendations for medication.
While negotiation of treatment decisions in the medical visit has long been recognized as an important interviewing skill, limited work has been done to investigate how doctors and patients negotiate what information is relevant in understanding the patient's problem. In this research we tested how the introduction of information reflecting both the patient's and physician's perspective is related to the patient's adherence to physician recommendations for medication. Introduction of information was defined as bi-directional if patients independently offered information or behavior as frequently as they provided the information or exhibited behavior that physicians requested. Thirty random samples of audiotaped dialogue were used to construct estimates of introduction of information during the history, examination, and consultation phases of initial ambulatory care visits of 45 older male patients. The data demonstrate that bi-directional introduction of information during the examination segment explains more than half of the variance in patient adherence to physician recommendations for new medication. These findings support the idea that physician willingness to allow patients to contribute input may contribute to the partnership's arrival at treatment decisions that have meaning for both.


Proteolytic activity and cooperative hemolytic effect of dermatophytes with different species of bacteria.
Globally, dermatophytes are the most common filamentous group of fungi causing cutaneous mycoses. Dermatophytes were shown to secrete a multitude of enzymes that play a role in their pathogenesis. There is limited data on co-hemolytic (CAMP-like) effect of different bacterial species on dermatophyte species. In this study, we sought to the evaluate exoenzyme activity and co-hemolytic effect of four bacteria on clinical dermatophytes isolated from patients in Shiraz, Iran. A total of 84 clinical dermatophyte species were isolated from patients suffering dermatophytosis and identified by conventional methods. Hemolytic activity was evaluated with Columbia 5% sheep blood agar. Proteolytic activity was determined by plate clearance assay method, using gelatin 8% agar. CAMP-like factor was evaluated with four bacteria, namely, S. areus, S.saprophyticus, S.pyogenes, and S.agalactiae. Fisher's exact test was run for statistical analysis. T. mentagrophytes was the most predominant agent (27 [32.1%]) followed by T. verrucosum(20 [23.8%]), T. tonsurans (10 [11.9%]), Microsporum canis (7 [8.3%]), T. rubrum (6 [7.1%]), E. floccosum (6 [7.1%]), M. gypseum (5 [6%]), and T. violaceum (3[3.6%]). The most common clinical area of dermatophytosis was the skin. All the isolates expressed the zone of incomplete alpha hemolysis. All the isolates had CAMP- positive reaction with S. aureus and the other bacteria were CAMP-negative. All the isolates expressed proteolytic activity and no significant differences were noted among diverse genera of dermatophytes and severities of proteolytic activity. This study indicated that hemolysin and proteolytic enzymes potentially play a role in dermatophyte pathogenesis and S. aureus could be considered as a main bacterium for creation of co-hemolytic effect in association with dermatophyte species.


Proximal tarsal attachments of the levator aponeurosis: implications for blepharoptosis repair.
To examine the tarsal attachments of the levator aponeurosis. Experimental anatomic study. Sixteen orbits from 12 fresh frozen white cadavers. Eight specimens served as controls. In the remaining 8 specimens from 4 cadavers, the upper eyelid was everted. All specimens then were fixed in formalin. The age, sex, and laterality were recorded in both groups. The eyelid lamellae and tarsal attachments of the levator aponeurosis in particular were examined microscopically. Lamellar and nonlamellar ocular anatomic features and the relationships of the preaponeurotic and postaponeurotic spaces were measured. Histologic findings of the extent and pattern of the tarsal attachments of the levator aponeurosis in relation to the tarsus and Müller's muscle and of the changes in the lamellae in eyelid eversion. The demographic and baseline anatomic characteristics of both the noneverted control and everted eyelid groups were similar. In comparing everted with noneverted controls, the preaponeurotic space was significantly shorter (6.22 and 10.61 mm, respectively; P = 0.003) and the preaponeurotic-to-postaponeurotic space ratio was halved (0.57 and 1.16, respectively; P = 0.005). Although the distance from the superior tarsal border to Whitnall's ligament increased significantly in everted versus noneverted eyes (14.65 and 11. 03 mm, respectively; P = 0.016), there was no significant difference in the length of postaponeurotic space in the 2 groups (11.07 and 9.69 mm, respectively; P = 0.370). The levator aponeurosis attached to the anterior tarsus in both groups. The proximal point of attachment was the superior border of the tarsal plate, adjacent to the insertion of Müller's muscle tendon. The deeper aponeurotic fibers and Müller's muscle attach proximally at the superior tarsal border. Upon eyelid eversion, the 2 lamellae move as a unit and the postaponeurotic space remains stable. A proximal tarsal attachment suggests that blepharoptosis procedures that advance an involutional or disinserted levator aponeurosis onto to the superior tarsus approximate that aspect of native anatomic features. In addition, posterior surgical approaches that address Müller's muscle may involve resections in closer proximity to the aponeurosis than previously thought. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Place conditioning of mice with the NMDA receptor antagonists, eliprodil and dizocilpine.
Effects of noncompetitive and competitive NMDA receptor antagonists have been repeatedly characterized using place conditioning models. The present study aimed to characterize the effects in mice of another NMDA receptor antagonist acting at polyamine binding site, eliprodil. Five-day conditioning with eliprodil (1-30 mg/kg, i.p.) resulted in a dose-dependent avoidance of an eliprodil-paired compartment during post-conditioning tests. These effects were: (i) observed both with eliprodil and without drug, and (ii) less pronounced in individually housed mice subjected to repeated social defeats and mild footshocks prior to and during the conditioning period (compared to group-housed and individually housed nonstressed mice). In a parallel set of experiments, the effects of dizocilpine (MK-801; 0.03-0.3 mg/kg, i.p.) were evaluated using the same study design as for eliprodil. Conditioned place preference was established with the dizocilpine dose of 0.3 mg/kg and this effect was not affected by housing/stressing or drug exposures during the test.


Ideas versus money: a conversation with Jean-Louis Sarbib. Interview by Philip Musgrove.
Philip Musgrove interviewed Jean-Louis Sarbib for Health Affairs on 23 May 2005 in a wide-ranging discussion of the Bank's experience with global health issues, including where the Bank has been most successful (disease control) or most frustrated (health systems). Since 1985 the World Bank has committed a total of dollar 22.6 billion to health projects; it is the largest source of development assistance for health.


Utilizing imaging mass spectrometry to analyze microbial biofilm chemical responses to exogenous compounds.
Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) is an appealing label-free method for imaging biological samples which focuses on the spatial distribution of chemical signals. This approach has been used to study the chemical ecology of microbes and can be applied to study the chemical responses of microbes to treatment with exogenous compounds. Specific conjugated cholic acids such as taurocholic acid (TCA), have been shown to inhibit biofilm formation in the enteric pathogen Vibrio cholerae and MALDI-IMS can be used to directly observe the chemical responses of V. cholerae biofilm colonies to treatment with TCA. A major challenge of MALDI-IMS is optimizing the sample preparation and drying for a particular growth condition and microbial strain. Here we demonstrate how V. cholerae is cultured and prepared for MALDI-IMS analysis and highlight critical steps to ensure proper sample adherence to a MALDI target plate and maintain spatial distributions when applying this technique to any microbial strain. We additionally show how to use both manual interrogation and statistical analyses of MALDI-IMS data to establish the adequacy of the sample preparation protocol. This protocol can serve as a guideline for the development of sample preparation techniques and the acquisition of high quality MALDI-IMS data.


Value of thyroid transcription factor-1 and surfactant apoprotein A in the differential diagnosis of pulmonary carcinomas: a study of 109 cases.
Thyroid transcription factor-1 (TTF-1) and surfactant apoprotein A (SP-A) belong to tissue-specific markers expressed in the normal respiratory epithelium. Both proteins are expressed in some lung carcinomas, and they have potential diagnostic use. We performed an immunohistochemical study on 109 tumors to determine the usefulness of monoclonal SP-A (PE-10) and TTF-1 (8G7G3/1) antibodies in distinguishing primary and metastatic lung carcinomas ( n=54) from a broad spectrum of nonpulmonary tumors ( n=55). An immunoperoxidase method using a streptavidin-biotin kit was applied on paraffin sections. We found positive results for TTF-1 and SP-A in 75% and 46% of pulmonary adenocarcinomas and in 50% and 25% of pulmonary non-neuroendocrine large cell carcinomas (LCCs), respectively. Small cell lung carcinomas were TTF-1 positive in 89% of cases and completely negative for SP-A. Squamous cell carcinomas and carcinoid tumors were negative for both proteins. In the group of nonpulmonary tumors, TTF-1 was detected in 8 of 11 thyroid carcinomas and SP-A in 1 of 6 colorectal carcinomas. Other tumors, including seven cases of pleural mesothelioma, were negative for both TTF-1 and SP-A. The expression of both antibodies was independent of primary and metastatic sites of the tumor. We observed a significant decrease of SP-A immunoreactivity in poorly differentiated lung adenocarcinomas. The combination of anti-TTF-1 with anti-SP-A does not increase the diagnostic usefulness of TTF-1 alone. Because of its diagnostic utility TTF-1 should be added to a panel of antibodies used for assessing tumors of unknown origin.


Global navigation in migratory birds: tracks, strategies, and interactions between mechanisms.
The advancing development of tracking techniques has led to fascinating new insights into avian migration, documenting the immense diversity, complexity, and flexibility of this phenomenon. Tracking studies so far have confirmed many findings from ringing recoveries and cage studies, for example, the change from flying innate compass courses in the first migration to true navigation, as experienced migrants head toward familiar goals. First attempts to analyze the navigational mechanisms by tracking manipulated migrants indicate strong parallels to those of homing pigeons. Findings suggesting that the magnetic compass of migrants is regularly calibrated by the pattern of polarized light could not be replicated with a number of other birds, pointing out differences between species and possibly region and phases of migration. Tracking has become a valuable tool, complimenting traditional methods by documenting migration behavior in the wild; whether it can be used to further unveil the navigational mechanisms of migrants and the factor used remains an open question.


Combination of Biochar and Trichoderma harzianum Can Improve the Phytoremediation Efficiency of Brassica juncea and the Rhizosphere Micro-Ecology in Cadmium and Arsenic Contaminated Soil.
Phytoremediation is an environment-friendly method for toxic elements remediation. The aim of this study was to improve the phytoremediation efficiency of Brassica juncea and the rhizosphere soil micro-ecology in cadmium (Cd) and arsenic (As) contaminated soil. A field experiment was conducted with six treatments, including a control treatment (CK), two treatments with two contents of Trichoderma harzianum (T1: 4.5 g m-2; T2: 9 g m-2), one biochar treatment (B: 750 g m-2), and two combined treatments of T1B and T2B. The results showed Trichoderma harzianum promoted the total chlorophyll and translocation factor of Brassica juncea, while biochar promoted plant biomass compared to CK. T2B treatment showed the best results, which significantly increased Cd accumulation by 187.49-308.92%, and As accumulation by 125.74-221.43%. As a result, the soil's total Cd content was reduced by 19.04% to 49.64% and total As contents by 38.76% to 53.77%. The combined amendment increased the contents of soil available potassium, phosphorus, nitrogen, and organic matter. Meanwhile, both the activity of glutathione and peroxidase enzymes in plants, together with urease and sucrase enzymes in soil, were increased. Firmicutes (dominant bacterial phylum) and Ascomycota (dominant fungal phylum) showed positive and close correlation with soil nutrients and plant potentially toxic elements contents. This study demonstrated that phytoremediation assisted by biochar and Trichoderma harzianum is an effective method of soil remediation and provides a new strategy for enhancing plant remediation efficiency.


Anticipating the future: automatic prediction failures in schizophrenia.
People with schizophrenia often misperceive sensations and misinterpret experiences, perhaps contributing to psychotic symptoms. These misperceptions and misinterpretations might result from an inability to make valid predictions about expected sensations and experiences. Healthy normal people take advantage of neural mechanisms that allow them to make predictions unconsciously, facilitating processing of expected sensations and distinguishing the expected from the unexpected. In this paper, we focus on two types of automatic, unconscious mechanisms that allow us to predict our perceptions. The first involves predictions made via innate mechanisms basic to all species in the animal kingdom - the efference copy and corollary discharge mechanisms. They accompany our voluntary movements and allow us to suppress sensations resulting from our actions. We study this during talking, and show that auditory cortical response to the speech sounds during talking is reduced compared to when they are played back. This suppression is reduced in schizophrenia, suggesting a failure to predict the sensations resulting from talking. The second mechanism involves implicitly learning what to expect from the current context of events. We study this by observing the brain's response to an unexpected repetition of an event, when a change would have been predicted. That patients have a reduced response suggests they failed to predict that it was time for a change. Both types of predictions should happen automatically and effortlessly, allowing for economic processing of expected events and orientation to unexpected ones. These prediction failures characterize the diagnosis of schizophrenia rather than reflecting specific symptoms.


Canadian news. Concerns raised about new immigration rules.
A new immigration law has been passed and will come into force in the near future. Community organizations have been critical of the proposed Regulations that will accompany the new law. Meanwhile, the federal government has instituted mandatory HIV testing of potential immigrants. Concerns have been voiced about how this testing will be carried out.


Association of common and rare variants of SCN10A gene with sudden unexplained nocturnal death syndrome in Chinese Han population.
Sudden unexplained nocturnal death syndrome (SUNDS) remains an autopsy negative entity with unknown etiology to both forensic pathologists and physicians. The electrocardiogram (ECG) characteristics and clinical phenotype of SUNDS survivors strongly suggest that SUNDS shares some similarities with Brugada syndrome (BrS). Recently, the variants of sodium channel Nav 1.8 coding gene SCN10A were identified to be associated with BrS. Here, we investigated the association of SCN10A gene variants with 105 sporadic SUNDS victims and 22 BrS cases in the Chinese Han population. A total of 6 rare mutations and 16 polymorphisms were detected in SUNDS victims. Of the six rare mutations, two were putative pathogenic mutations (F386C and R1263*), one was a likely pathogenic mutation (R14H), and the other three were predicted as benign (R817Q, T1181M, and P1683S). As for the 16 polymorphisms, 1 was a novel polymorphism (c.4144-84G>A) located in intron 24, and the rest were reported previously including one polymorphism (c.2884A>G [I962V]) which showed a statistically significant difference in allele frequency (p = 0.044) between SUNDS and the control group. There were also 5 rare mutations and 15 polymorphisms detected in BrS cases. This is the first report of common and rare variants of SCN10A gene in SUNDS and BrS in the Chinese Han population, which provides the genetic epidemiological evidence that SCN10A may be a novel susceptibility gene for SUNDS and account for approximately 3 % of SUNDS in China.


The Clinical Usefulness of Targeted Temperature Management in Acute Ischemic Stroke with Malignant Trait After Endovascular Thrombectomy.
Targeted temperature management (TTM) may be more beneficial after endovascular treatment (EVT) in patients with a large ischemic core. Therefore, we assessed the usefulness of TTM for such patients from a multicenter endovascular registry. Anterior circulation stroke patients who underwent endovascular recanalization were included; acute ischemic stroke with malignant traits was designated as (1) baseline Alberta Stroke Program Early CT Score (ASPECTS) below 6 and (2) diffusion-weighted imaging (DWI) lesion volume measurement (> 82 ml) or National Institutes of Health Stroke Scale score > 20 and item Ia > 0. TTM (34.5 °C) was maintained for at least 48 h. We evaluated baseline demographics, risk factors, EVT parameters, and clinical outcomes between the TTM and non-TTM groups. Among the 548 patients, the TTM group (n = 91) significantly had a lower baseline ASPECTS (p < 0.001) and a higher DWI volume (p < 0.001) than the non-TTM group (n = 457). TTM group had a lower prevalence of favorable outcome (0-2 of modified Rankin Scale at 3 months; p = 0.008) than the non-TTM group. In a subgroup analysis of malignant trait patients (n = 80), TTM patients (n = 28) had more favorable outcome (32.1% vs. 7.7% p = 0.009) and less hemorrhagic transformation (none vs. any hemorrhage, p = 0.007) than non-TTM patients (n = 52). After adjusting for potential outcome predictors, TTM (odds ratio [OR] 4.63; confidence interval [CI] 1.20-17.89; p = 0.026) and hypertension (OR 0.18; CI 0.04-0.74; p = 0.018) were found to be independent determinants. Our data suggest that TTM attenuates impending hemorrhagic transformation and leads to favorable clinical outcomes in EVT patients with malignant trait.


Toxic shock syndrome: a review of the literature.
A review of toxic-shock syndrome is presented. The epidemiology, clinical features, present and possible future management are discussed.


Cryo-EM structure of bifunctional malonyl-CoA reductase from Chloroflexus aurantiacus reveals a dynamic domain movement for high enzymatic activity.
The platform chemical 3-hydroxypropionic acid is used to synthesize various valuable materials, including bioplastics. Bifunctional malonyl-CoA reductase is a key enzyme in 3-hydroxypropionic acid biosynthesis as it catalyzes the two-step reduction of malonyl-CoA to malonate semialdehyde to 3-hydroxypropionic acid. Here, we report the cryo-EM structure of a full-length malonyl-CoA reductase protein from Chloroflexus aurantiacus (CaMCRFull). The EM model of CaMCRFull reveals a tandem helix architecture comprising an N-terminal (CaMCRND) and a C-terminal (CaMCRCD) domain. The CaMCRFull model also revealed that the enzyme undergoes a dynamic domain movement between CaMCRND and CaMCRCD due to the presence of a flexible linker between these two domains. Increasing the flexibility and extension of the linker resulted in a twofold increase in enzyme activity, indicating that for CaMCR, domain movement is crucial for high enzyme activity. We also describe the structural features of CaMCRND and CaMCRCD. This study reveals the protein structures underlying the molecular mechanism of CaMCRFull and thereby provides valuable information for future enzyme engineering to improve the productivity of 3-hydroxypropionic acid.


Selective resistance of L1210 cell lines to inhibitors directed at the subunits of ribonucleotide reductase.
L1210 cell lines were generated which were resistant to specific ribonucleotide reductase inhibitors. Hydroxyurea-resistant L1210 cells (HU-7) were cross-resistant to IMPY but sensitive to deoxyadenosine and deoxyguanosine. Deoxyadenosine-resistant L1210 cells (Y-8) were cross-resistant to 2-fluorodeoxyadenosine and showed only a small increase in resistance to hydroxyurea or IMPY. L1210 cells which were generated in the presence of deoxyadenosine/EHNA/IMPY/Desferal were markedly resistant to deoxyadenosine, deoxyguanosine and 2-fluorodeoxyadenosine with moderate increases in resistance to IMPY. The HU-7, Y-8 and ED2 cell lines were sensitive to the inhibitory effects of MAIQ and HAG-IQ. The HU-7 L1210 cell line had elevated levels of ribonucleotide reductase activity and this activity showed normal inhibition by hydroxyurea, IMPY, dATP, dGTP and dTTP. The Y-8 L1210 cell line did not have elevated levels of ribonucleotide reductase activity, but had altered allosteric properties relative to dATP. The ED2 L1210 cell line had elevated levels of ribonucleotide reductase activity and had altered allosteric properties relative to dATP. These data show that resistance to ribonucleotide reductase inhibitors is specifically generated in response to the particular drug. The biochemical basis can be related to either increased levels of ribonucleotide reductase activity or loss of feedback control by dATP or both.


Evaluation of the physicochemical and functional stability of diluted REMSIMA® upon extended storage--A study compliant with NHS (UK) guidance.
A newly licensed biosimilar product containing infliximab as the active pharmaceutical ingredient has recently been marketed under the brand name Remsima®. We have evaluated the stability of Remsima® diluted in sodium chloride solution and stored in polyolefin bags at 2-8°C using a range of techniques to assess the physico-chemical and functional integrity of the drug over time. The methods and techniques employed are fully compliant with NHS (UK) guidance for evaluating the stability of biologicals, enabling the data to be used for the application of an extended shelf-life to Remsima products in the UK, when prepared under a Section 10 exemption or a Specials Licence. The results clearly demonstrate physico-chemical and functional stability of the drug over the 7 day period of the study, when prepared as described here under aseptic conditions in accordance with the Summary of manufacturers Product Characteristics.


Perfectionism, responsibility and obsessive-compulsive symptoms.
Although both perfectionism and responsibility have been associated with OCD at a theoretical level, responsibility has been the focus of a number of recent articles. This study was conducted in order to empirically test the relative importance of perfectionism and responsibility in Obsessive-Compulsive symptoms. Perfectionism and two measures of responsibility showed moderate correlations with Obsessive-Compulsive symptoms. A hierarchical regression analysis revealed that although responsibility accounted for more variance, perfectionism was still a significant predictor of Obsessive-Compulsive symptoms, once responsibility had been partialled out. These results suggest that although responsibility is related to OC symptoms, perfectionism is also independently associated. While responsibility has received much attention lately from OCD theorists and clinicians, perfectionism may also play a significant if underestimated role in some OC patients. The results are discussed in terms of their implications for current cognitive models and treatment procedures that give responsibility a central role in OCD. A new definition of perfectionism is also proposed.


Nematicidal triterpenoids from Lantana camara.
A new triterpene, lancamarolide (1), and seven known triterpenes, oleanonic acid (2), lantadene A (3), 11α-hydroxy-3-oxours-12-en-28-oic acid (4), betulinic acid (5), lantadene B (6), and lantaninilic acid (7) were isolated from the aerial parts of Lantana camara in the course of bioassay-guided isolation, and their nematicidal activities against Meloidogyne incognita, the root knot nematode, were carried out. Oleanonic acid was found to be the most active compound and exhibited 80% mortality after 72 h at 0.0625% concentration, which is comparable with that of the standard furadan.


The short- and long-term effect of membrane anatomy-guided laparoscopic D2 lymphadenectomy plus regional complete mesogastrium excision for locally advanced gastric cancer.
Retrospectively analyzed the short- and long-term efficacy between laparoscopic D2 lymphadenectomy plus regional complete mesogastrium excision (D2 + rCME) and traditional laparoscopic D2 in the treatment of patients with locally advanced gastric cancer (LAGC), in order to obtain more evidence for D2 + rCME gastrectomy. A total of 599 LAGC patients who underwent laparoscopy-assisted radical gastrectomy from January 2014 to December 2019, including 367 cases in the D2 + rCME group and 232 cases in the D2 group. Intraoperative and postoperative clinicopathological parameters, postoperative complications and long-term survival in the two groups were statistically analyzed. No significant differences in the positive rate of mesogastric tumor deposits, the number of positive lymph nodes and postoperative length of stay were found between the two groups (P > 0.05). In the D2 + rCME group, intraoperative blood loss was significantly reduced (84.20 ± 57.64 ml vs. 148.47 ± 76.97 ml, P < 0.001), the time to first postoperative flatus and first liquid diet intake were significantly shortened (3[2-3] days vs. 3[3-3] days, P < 0.001; 7[7-8] days vs. 8[7-8] days, P < 0.001), and the number of lymph nodes dissected was greater (43.57 ± 16.52 pieces vs. 36.72 ± 13.83 pieces, P < 0.001). The incidence of complications did not significantly differ between the D2 + rCME group (20.7%) and D2 group (19.4%) (P > 0.05). Although there was no statistically difference in 3-year OS and DFS between the two groups. However, the trend was better in D2 + rCME group. In subgroup analysis, patients with positive tumor deposits (TDs) in the D2 + rCME group had significantly better 3-year DFS compared With D2 group (P < 0.05). Laparoscopic D2 + rCME is safe and feasible for the treatment of LAGC and is characterized by less bleeding, greater lymph node dissection and rapid recovery, without increasing postoperative complications. D2 + rCME group showed a better trend of long-term efficacy, especially significant beneficial for LAGC patients who with positive TDs.


Surfactant-Templated Synthesis of Polypyrrole Nanocages as Redox Mediators for Efficient Energy Storage.
Preparation of conducting-polymer hollow nanoparticles with different diameters was accomplished by surfactant templating. An anionic surfactant, namely sodium dodecylbenzenesulfonate, formed vesicles to template with the pyrrole monomer. Subsequent chemical oxidative polymerization of the monomer yielded spherical polypyrrole (PPy) nanoparticles with hollow interiors. The diameter of the hollow nanoparticles was easily controlled by adjusting the concentration of the surfactant. Subsequently, the size-dependent electrochemical properties of the nanoparticles, including redox properties and charge/discharge behavior, were examined. By virtue of the structural advantages, the specific capacitance (max. 326 F g(-1)) of PPy hollow nanoparticles was approximately twice as large as that of solid PPy nanospheres. The hollow PPy nanostructure can easily be used as a conductive substrate for the preparation of metal/polymer nanohybrids through chemical and electrochemical deposition. Two different pseudocapacitive metal-oxide clusters were readily deposited on the inner and outer surfaces of the hollow nanoparticles, which resulted in an increase in the specific capacitance to 390 F g(-1). In addition, the hollow nanoparticles acted as a nanocage to prevent metal ion leaching during charge/discharge, thus allowing an excellent capacitance retention of ca. 86%, even following 10,000 cycles.


Video Urodynamic Study in Female Adults With Air-filled Catheters: A Health-care Training Video.
To take the first step toward standardization of UDS with air-filled catheters, we present a video documenting a procedure for performing video UDS with air-filled catheters in female adults. According to The International Consultation on Incontinence (ICS), the aim of urodynamic studies (UDS) in clinical practice is to evaluate a patient's lower urinary tract function with at least 1 complete and representative filling-voiding-post-voiding cycle by testing with relevant pressures and flowmetry.1 International guidelines state that UDS is preferably performed with fluid-filled catheters.2,3 However, although air-filled catheters are widely used, further research is needed before these catheters can be recommended for routine clinical use.4 To our knowledge, no guide on how to perform UDS with air-filled catheters has been published. The UDS was conducted according to local protocol. The ICS recommendations mentioned above were used as a template for this protocol. Intravesical, intraurethral, and abdominal pressure were measured. The cysto-urethrometry filling cycle and pressure-flow study were performed in sitting position. Fluoroscopy was performed during filling and voiding phase at fixed points. Before starting the filling cycle, the patient was verbally instructed with visual aids (Fig. 1) to report bladder sensation. Filling rate was 10% of the largest voiding flow rate reported on the frequency volume chart. Initial baseline pressure was measured, and a cough pressure response test was performed. Our procedure for video UDS with air-filled catheters in a female adult was demonstrated in an instruction video. An instruction video on a standardized UDS with air-filled catheters in female adults is presented to take the first step toward standardization and for the benefit of health-care workers performing such tests.


Test-positive rate at CT colonography is increased by rectal bleeding and/or unexplained weight loss, unlike other common gastrointestinal symptoms.
We evaluated the rate of significant colonic and extra-colonic abnormalities at computed tomography colonography (CTC), according to symptoms and age. We retrospectively evaluated 7361 consecutive average-risk subjects (3073 males, average age: 60.3 ± 13.9; range 18-96 years) for colorectal cancer (CRC) who underwent CTC. They were divided into three groups according to clinical symptoms: 1343 asymptomatic individuals (group A), 899 patients with at least one "alarm" symptom for CRC, including rectal bleeding and unexplained weight loss (group C), and 5119 subjects with other gastrointestinal symptoms (group B). Diagnostic and test-positive rates of CTC were established using optical colonoscopy (OC) and/or surgery as reference standard. In addition, clinically significant extra-colonic findings were noted. 903 out of 7361 (12%, 95% confidence interval (CI) 0.11-0.13) subjects had at least one clinically significant colonic finding at CTC. CTC true positive fraction and false positive fraction were respectively 637/642 (99.2%, 95%CI 0.98-0.99) and 55/692 (7.95%, 95%CI 0.05-0.09). The pooled test-positive rate in group C (138/689, 20.0%, 95%CI 0.17-0.23) was significantly higher than in both groups A (79/1343, 5.9%, 95%CI 0.04-0.07) and B (420/5329, 7.5%, 95%CI 0.07-0.08) (p < 0.001). Aging and male gender were associated to a higher test positive rate. The rate of clinically significant extra-colonic findings was significantly higher in group C (44/689, 6.4%, 95%CI 0.04-0.08) versus groups A (26/1343, 1.9%, 95%CI 0.01-0.02) and B (64/5329, 1.2%, 95%CI 0.01-0.02) (p < 0.001). Both test-positive and significant extra-colonic finding rates at CTC are significantly increased in the presence of "alarm" gastrointestinal symptoms especially in older patients.


Acetylation of SUMO2 at lysine 11 favors the formation of non-canonical SUMO chains.
Post-translational modifications by ubiquitin-related SUMO modifiers regulate cellular signaling networks and protein homeostasis. While SUMO1 is mainly conjugated to proteins as a monomer, SUMO2/3 can form polymeric chains. Poly-SUMOylation is best understood in the SUMO-targeted ubiquitin ligase (StUbL) pathway, where chains prime proteins for subsequent ubiquitylation by StUbLs. SUMO chains typically form in response to genotoxic or proteotoxic stress and are preferentially linked via lysine 11 of SUMO2/3. Here, we report that K11 of SUMO2/3 undergoes reversible acetylation with SIRT1 being the K11 deacetylase. In a purified in vitro system, acetylation of SUMO2/3 impairs chain formation and restricts chain length. In a cellular context, however, K11 acetyl-mimicking SUMO2 does not affect the StUbL pathway, indicating that in cells non-canonical chains are more prevalent. MS-based SUMO proteomics indeed identified non-canonical chain types under basal and stress conditions. Importantly, mimicking K11 acetylation alters chain architecture by favoring K5- and K35-linked chains, while inhibiting K7 and K21 linkages. These data provide insight into SUMO chain signaling and point to a role of K11 acetylation as a modulator of SUMO2/3 chains.


Course of activities of daily living in nursing home residents with dementia from admission to 36-month follow-up.
Dementia is affecting both the person with the disease and the family members. It is associated with nursing home admission, and a reduced ability to perform personal activities of daily living (P-ADL). The aim of this study was to examine the association between the severity of dementia and P-ADL function, and to study if additional factors such as neuropsychiatric symptoms, type of nursing home unit, and use of medication were associated with P-ADL function. A total of 582 nursing home residents with dementia, included at admission to the nursing home, were followed with biannual assessments for 36 months. P-ADL was assessed using the Physical Self-Maintenance scale, and severity of dementia was measured with the Clinical Dementia Rating scale. In addition, neuropsychiatric symptoms, general physical health, and use of medications were assessed at the same time points. Demographic information was collected at baseline. Linear mixed models were estimated. There was a significant (p < 0.05) non-linear decline in P-ADL function over time in analysis not adjusting for any characteristics. More severe dementia at baseline and at the follow-up assessments was associated with lower P-ADL function (p < 0.001), with the association being stable over time. A higher level of neuropsychiatric symptoms, not using anti-dementia medication, being in a regular care unit as compared to a special care unit and having poor/fair general physical health as compared to good/excellent, were associated with a lower P-ADL function. The association between more severe dementia and lower P-ADL function was stable over a 36-month follow-up period of nursing home residents with dementia. Health care planners and clinicians should be aware of this when planning for and treating nursing home residents.


pH-dependent entry of chikungunya virus into Aedes albopictus cells.
The chikungunya virus (CHIKV) recently caused explosive outbreaks in Indian Ocean islands and India. During these episodes, the virus was mainly spread to humans through the bite of the mosquito Aedes albopictus. Concomitantly to the description of symptoms of an unexpected severity in infants and elderly patients, a viral genome microevolution has been highlighted, in particular consisting in the acquisition of an A226V mutation in the gene encoding envelope glycoprotein E1, which was later found to confer an increased fitness for A. albopictus. We previously decrypted the entry pathway used by CHIKV to infect human epithelial cells and showed that these mechanisms are modulated by the E1-A226V mutation. In this report we investigated the conditions for CHIKV entry into mosquito cells and we assessed the consequence of E1 gene mutation on these parameters. Our main findings indicate that CHIKV infection of A. albopictus cell lines is sensitive to Bafilomycin A1 and chloroquine and to membrane cholesterol depletion. The E1-226V mutated LR-OPY1 isolate collected during the 2005 outbreak in La Réunion replicated more efficiently than the 37997 African reference strain in C6/36 cells. Moreover, the LR-OPY1 strain displayed greater membrane cholesterol dependence and was more sensitive to inhibition of endosomal pH acidification. Finally, using electron microscopy, we imaged CHIKV entry into C6/36 cells. Our data support that CHIKV is endocyted into A. albopictus cells and requires membrane cholesterol as well as a low-pH environment for entry. These features are modulated in some extent by the A226V mutation in the E1 gene of the LR-OPY1 isolate. Altogether, our data provide information regarding the pathways used by CHIKV to infect A. albopictus cells.


Prediction and reduction of motion artifacts in free-breathing dynamic contrast enhanced CT perfusion imaging of primary and metastatic intrahepatic tumors.
To develop and evaluate a method for predicting and reducing motion artifacts in free-breathing liver perfusion computed tomography (CT) scanning with couch shuttling and to compare tumor and liver parenchyma perfusion values. Thirty patients (23 males, 7 females, median age of 74 years) with primary or metastatic intrahepatic tumors underwent dynamic contrast enhanced CT scans with axial shuttling. A semiautomatic respiratory motion correction algorithm was applied to align the acquired images along the z-axis. Perfusion maps were generated using the dual-input Johnson-Wilson model. Root mean squared deviation (RMSD) maps of the model fit to the pixel time-density curves were calculated. Precorrection RMSD correlated positively with magnitude of change in functional values resulting from motion. Blood flow, arterial blood flow, and permeability surface product were significantly increased in tumor compared to normal tissue (P < .05), blood volume was significantly reduced in tumor compared to normal tissue (P < .05). In a subgroup of patients with high-amplitude motion significant difference was observed between uncorrected and motion correction blood flow maps. Patients can breathe freely during hepatic perfusion imaging if retrospective motion correction is applied to reduce motion artifacts. RMSD provides a regional assessment of motion induced artifacts in liver perfusion maps.


The power of neuropeptide precursor sequences to reveal phylogenetic relationships in insects: A case study on Blattodea.
Recent state-of-the-art analyses in insect phylogeny have exclusively used very large datasets to elucidate higher-level phylogenies. We have tested an alternative and novel approach by evaluating the potential phylogenetic signals of identified and relatively short neuropeptide precursor sequences with highly conserved functional units. For that purpose, we examined available transcriptomes of 40 blattodean species for the translated amino acid sequences of 17 neuropeptide precursors. Recently proposed intra-ordinal relationships of Blattodea, based on the analysis of 2370 protein-coding nuclear single-copy genes (Evangelista et al., 2019), were corroborated with maximum support. The functionally different precursor units were analyzed separately for their phylogenetic information. Although the degree of information was different in the different sequence motifs, all precursor units contained phylogenetic informative data at the ordinal level, and their separate analysis did not reveal contradictory topologies. This study is the first comprehensive exploitation of complete neuropeptide precursor sequences of arthropods in such a context and demonstrates the applicability of these rather short but conserved sequences for an alternative, fast and simple analysis of phylogenetic relationships.


Adherence to oxygenation and ventilation targets in mechanically ventilated premature and sick newborns: a retrospective study.
Ventilator treatment exposes newborns to both hyperoxemia and hyperventilation. It is not known how common hyperoxemia and hyperventilation are in neonatal intensive care units in Norway. The purpose of this study was to assess the quality of current care by studying deviations from the target range of charted oxygenation and ventilation parameters in newborns receiving mechanical ventilation. Single centre, retrospective chart review that focused on oxygen and ventilator treatment practices. The bedside intensive care charts of 138 newborns reflected 4978 hours of ventilator time. Arterial blood gases were charted in 1170 samples. In oxygen-supplemented newborns, high arterial pressure of oxygen (PaO2) values were observed in 87/609 (14%) samples. In extremely premature newborns only 5% of the recorded PaO2 values were high. Low arterial pressure of CO2 (PaCO2) values were recorded in 187/1170 (16%) samples, and 64 (34%) of these were < 4 kPa. Half of all low values were measured in extremely premature newborns. Tidal volumes above the target range were noted in 22% of premature and 20% of full-term newborns. There was a low prevalence of high PaO2 values in premature newborns, which increased significantly with gestational age (GA). The prevalence of low PaCO2 values was highest among extremely premature newborns and decreased with increasing GA. Further studies are needed to identify whether adherence to oxygenation and ventilation targets can be improved by clearer communication and allocation of responsibilities between nurses and physicians.


The cortisol response in policemen: intraindividual variation, not concentration level, predicts truncal obesity.
Chronic stress, characteristic of police work, affects the hypothalamic-pituitary-adrenal axis' control of cortisol production. Capacity to vary cortisol may be the appropriate measurement to interpret associations with chronic diseases, including obesity, best measured by variability within a person, not central tendency. On each of 217 policemen, 18 saliva specimens were obtained for cortisol. Statistical models examined the associations of within-subjects (W-S) cortisol standard deviation (SD) and W-S cortisol mean with waist circumference and four body composition indexes: BMI, and three derived from DEXA: fat-mass, and trunk and extremities lean-mass. Explained variance and the functional nature of associations are reported. Associations of anthropometrics with W-S cortisol mean were not statistically significant at P < 0.05; all associations with W-S cortisol SD were significant. The association of trunk lean mass index (LMIt ) with W-S cortisol SD dominated all models. Associations of W-S cortisol SD with other indexes vanished when models contained LMIt ; when any other index was included in models predicting LMIt , associations with W-S cortisol SD remained significant. The functional association between LMIt and W-S cortisol SD is progressively "hockey stick," monotonic increasing, and flattens at joint high values. Results support inferences that LMIt measures visceral adiposity and W-S cortisol variability appears to be an appropriate construct to measure in association with visceral adiposity. The "hockey stick" character of the association is consistent with other investigations suggesting obesity is associated with less W-S cortisol variation; however, the monotonic increase and flattening of association at increasing W-ScortisolSD values suggests a more complex association, potentially interpretable by allostasis models of causation.


The prediction approach of drug-induced liver injury: response to the issues of reproducible science of artificial intelligence in real-world applications.
In the previous study, we developed the generalized drug-induced liver injury (DILI) prediction model-ResNet18DNN to predict DILI based on multi-source combined DILI dataset and achieved better performance than that of previously published described DILI prediction models. Recently, we were honored to receive the invitation from the editor to response the Letter to Editor by Liu Zhichao, et al. We were glad that our research has attracted the attention of Liu's team and they has put forward their opinions on our research. In this response to Letter to the Editor, we will respond to these comments.


Pathogenetic mechanisms in essential hypertension. Analogies between a rat model and the human disease.
Essential hypertension is a genetic disease. Its phenotypic expression depends on the interaction between genetic and environmental factors. In prehypertensive rats of the Milan hypertensive strain (MHS) a genetically inherited increase of tubular reabsorption was found, which causes the increase of blood pressure. Studies of ion transport systems in these rats have shown that the Na-K cotransport activity is increased both in erythrocytes and in tubular cells of MHS rats compared with their normotensive controls (MNS) and that this alteration is genetically linked to the transmission of high blood pressure levels. Also, in young human normotensives prone to develop essential hypertension there is an abnormal pattern of renal function which could be in agreement with a primitive increase in tubular reabsorption. Studies of erythrocyte ion transport systems in these subjects suggest that at least in a subgroup of humans predisposed to develop essential hypertension a pathogenetic mechanism similar to the one proposed for the MHS rat can be at work.


A monopole antenna with cotton fabric material for wearable applications.
A monopole antenna operated at 2.45 GHz and embedded with artificial magnetic conductor (AMC) for wearable communication systems is investigated in this article. The proposed antenna is composed of a metalized loop radiator with a coplanar waveguide microstrip feedline which is affixed on a cotton fabric material substrate. As well, a cotton-based AMC surface is utilized to eliminate the body's absorbed radiation and enhance the gain of the antenna. It is composed of 5 × 5 array unit cells etched with I-shaped slots. Using this configuration, simulations show that the specific absorption rate (SAR) level was significantly reduced. Considering flat and rounded body parts, it was found that the SAR values averaged over 10 g at a distance of 1 mm away from the tissues model were only 0.18 W/kg and 0.371 W/kg, respectively. Additionally, the antenna gain was improved up to 7.2 dBi with an average radiation efficiency of 72%. Detailed analysis with experimental measurements of the cotton-based antenna for different operation scenarios is introduced. The measured data show a good correlation with the electromagnetic simulation results.


Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S): An update on basic science and clinical perspectives.
Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare, underrecognized, systemic small vessel disease caused by heterozygous C-terminal truncating TREX1 mutations. The disease is characterized by vascular retinopathy, focal neurological complaints, cognitive decline and a wide range of systemic manifestations, including Raynaud's phenomenon, anemia and liver and kidney disease. Eventually, RVCL-S leads to premature death. The underlying pathological finding in RVCL-S is a nonatherosclerotic, amyloid-negative angiopathy involving small arteries and capillaries. However, the exact mechanisms by which the truncated TREX1 protein causes angiopathy remains unknown. Timely recognition of this disease is important to slow down and treat complications of the disorder, but also to prevent unnecessary (invasive) diagnostic or therapeutic procedures. As we move forward, translational research combining basic science advances and clinical findings as well as studies focusing on natural history following RVCL-S patients at different disease stages, will be critical to help elucidate RVCL-S pathophysiology. These studies will also provide the tools to identify appropriate biomarkers and therapeutic agent options for RVCL-S patients.


Elemental Analysis of Kimchi Cabbage Leaves, Roots, and Soil and Its Potential Impact on Human Health.
In view of their rich mineral content and flavor, kimchi cabbage leaves and roots have high nutritional and medicinal values. In this study, we quantified major nutrient (Ca, Cu, Fe, K, Mg, Na, and Zn), trace (B, Be, Bi, Co, Ga, Li, Ni, Se, Sr, V, and Cr), and toxic (Pb, Cd, Tl, and In) elements in kimchi cabbage cultivation soil, leaves, and roots. The analysis method relied on inductively coupled plasma-optical emission spectrometry for major nutrient elements and inductively coupled plasma-mass spectrometry for trace and toxic elements and complied with the Association of Official Analytical Chemists (AOAC) guidelines. Kimchi cabbage leaves and roots featured high contents of K, B, and Be, while the contents of all toxic elements in all samples were below the WHO-stipulated threshold values and therefore did not pose any health risks. The distribution of elements was characterized by heat map analysis and linear discriminant analysis to reveal independent separation according to the content of each element. The analysis confirmed that there was a difference in content between the groups and that each group was independently distributed. This study may contribute to a better understanding of the complex relationships between plant physiology, cultivation condition, and human health.


Protein carboxyl methyltransferase from cow eye lens.
Protein carboxyl methyltransferase activity (S-adenosyl-L-methionine: protein carboxyl-0-methyltransferase; E.C. 18.104.22.168) has been detected in crude soluble extracts of cow eye lens. The activity incorporates methyl groups from S-adenosyl-L-methionine into endogenous lens proteins in vitro, and several of these species co-migrate electrophoretically with lens crystallins. A 2600-fold purification of the enzyme free of endogenous substrates was achieved by gel filtration and affinity chromatography. The lens methyltransferase has a native molecular weight of approximately 27,000, and catalyzes the substoichiometric incorporation of highly alkali-labile methyl ester groups into a broad range of protein substrates. The lens enzyme appears to be similar to that found in human erythrocytes, which specifically recognizes and modifies D-aspartic acid residues in aged proteins in a postulated degradative or racemization-repair pathway (McFadden, P.N., and Clarke, S. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 2460-2464).