Predicting Operative Outcomes in Patients with Liver Disease: Albumin-Bilirubin Score vs Model for End-Stage Liver Disease-Sodium Score.
The albumin-bilirubin score (ALBI) has recently been shown to have increased accuracy in predicting post-hepatectomy liver failure and mortality compared with the Model for End-Stage Liver Disease (MELD). However, the use of ALBI as a predictor of postoperative mortality for other surgical procedures has not been analyzed. The aim of this study was to measure the predictive power of ALBI compared with MELD-sodium (MELD-Na) across a wide range of surgical procedures. Patients undergoing cardiac, pulmonary, esophageal, gastric, gallbladder, pancreatic, splenic, appendix, colorectal, adrenal, renal, hernia, and aortic operations were identified in the 2015-2018 American College of Surgeons NSQIP database. Patients with missing laboratory data were excluded. Univariable analysis and receiver operator characteristic curves were performed for 30-day mortality and morbidity. Areas under the curves were calculated to validate and compare the predictive abilities of ALBI and MELD-Na. Of 258,658 patients, the distribution of ALBI grades 1, 2, 3 were 51%, 42%, and 7%, respectively. Median MELD-Na was 7.50 (interquartile range 6.43 to 9.43). Overall 30-day mortality rate was 2.7% and overall morbidity was 28.6%. Increasing ALBI grade was significantly associated with mortality (ALBI grade 2: odds ratio [OR] 5.24; p < 0.001; ALBI grade 3: OR 25.6; p < 0.001) and morbidity (ALBI grade 2: OR 2.15; p < 0.001; ALBI grade 3: OR 6.12; p < 0.001). On receiver operator characteristic analysis, ALBI outperformed MELD-Na with increased accuracy in several operations. ALBI score predicts mortality and morbidity across a wide spectrum of surgical procedures. When compared with MELD-Na, ALBI more accurately predicts outcomes in patients undergoing pulmonary, elective colorectal, and adrenal operations.


Triblock peptide-oligonucleotide chimeras (POCs): programmable biomolecules for the assembly of morphologically tunable and responsive hybrid materials.
Triblock peptide-oligonucleotide chimeras (POCs) consisting of peptides and oligonucleotides interlinked by an organic core are presented and their assembly behaviour is investigated. Several factors influence POC assembly, resulting in the formation of either vesicles or fibres. Design rules are introduced and used to predict and alter POC assembly morphology.


Electron paramagnetic resonance of Cu2+:Mb single crystal. Conformational changes.
Copper introduced into met-myoglobin crystals occupies various sites as indicated by electron paramagnetic resonance parameters. Cu2+ (A) is probably liganded to histidine A10, lysine A14, and asparagine GH4 (Banaszak et al., 1965) and shows superhyperfine interaction with a single (imidazole) nitrogen. Cu2+ (B) and Cu2+ (C) correspond to other anisotropic sites described in less detail. Cu2+ (A) exhibits a transition to an isotropic form with a transition temperature of 40.5 degrees C. This transition indicates a conformational change in myoglobin and could correspond to a motion of A helix away from the GH section. The transition temperature is 7 degrees C higher than the one previously reported (Atanasov, 1971) for myoglobin in solution.


Andrographolide promotes proliferative and osteogenic potentials of human placenta-derived mesenchymal stem cells through the activation of Wnt/β-catenin signaling.
The in vitro expansion and differentiation of mesenchymal stem cells derived from bone marrow (BM-hMSCs) are considered as potential therapeutic tools for clinical applications in bone tissue engineering and regenerative medicine. However, invasive sampling and reduction in number and proliferative capacity with age are the major limitations of BM-hMSCs. Recently, human placenta-derived MSCs (PL-hMSCs) obtained by a non-invasive procedure have attracted much interest. Attempts to increase the potential of PL-hMSCs would be an important paradigm in regenerative medicine. Herein, we examined the proliferative and osteogenic effect of andrographolide (AP) on PL-hMSCs. Mesenchymal stem cells were isolated from full-term normal human placentas and were characterized before using. Cell cytotoxicity and proliferative effect of AP were examined by MTT and BrdU assay, respectively. The non-toxicity concentrations of AP were further assessed for osteogenic effect determined by alkaline phosphatase (ALP) expression and activity, alizarin red staining, and osteoblast-specific gene expressions. Screening of genes involved in osteogenic differentiation-related pathways modulated by AP was explored by a NanoString nCounter analysis. PL-hMSCs generated in this study met the MSC criteria set by the International Society of Cellular Therapy. The non-cytotoxic concentrations of AP on PL-hMSCs are up to 10 μM. The compound increased PL-hMSC proliferation concomitant with increases in Wnt/β-catenin level and activity. It also enhanced osteogenic differentiation in association with osteoblast-specific mRNA expression. Further, AP promoted bone formation and increased bone structural protein level, osteocalcin, in osteoblastic cells. Gene screening analysis showed the upregulation of genes related to Wnt/β-catenin, TGFβ/BMP, SMAD, and FGF signaling pathways. We demonstrated, for the first time, the potential role of AP in promoting proliferation, osteogenic differentiation, and osteoblast bone formation of PL-hMSCs. This study suggests that AP may be an effective novel agent for the improvement of PL-hMSCs and stem cell-based therapy for bone regeneration.


Antiplatelet drugs: clinical pharmacology and therapeutic use.
Because platelets are so important in thrombus formation, drugs which inhibit platelet function (the 'antiplatelet drugs') have considerable potential as antithrombotic agents. Among the antiplatelet drugs, only aspirin, sulphinpyrazone, dipyridamole, hydroxychloroquine, and clofibrate have had wide clinical trial. Their effects on platelet metabolism differ. Aspirin prevents platelet prostaglandin synthesis by acetylating and irreversibly inactivating platelet prostaglandin synthetase, while sulphinpyrazone is a reversible inhibitor of the same enzyme. Both aspirin and sulphinpyrazone impair the platelet release reaction and reduce platelet aggregation, but neither prevents platelet adhesion to the subendothelium or to foreign surfaces. On the other hand, dipyridamole reduces platelet adhesion as well as aggregation, probably by inhibiting phosphodiesterase and so raising platelet cyclic AMP levels. The effects of hydroxychloroquine and clofibrate have been less well defined. As the antiplatelet drugs form a diverse group of substances with differing effects on platelet function, it is hardly surprising that every potential clinical application of each antiplatelet drug or drug combination has had to be tested separately, and that these drugs have not proved to be equally effective. One or more antiplatelet drugs have now been evaluated in each of the following situations.


α-Gal Nanoparticles in CNS Trauma: I. In Vitro Activation of Microglia Towards a Pro-Healing State.
Macrophages and microglia play critical roles after spinal cord injury (SCI), with the pro-healing, anti-inflammatory (M2) subtype being implicated in tissue repair. We hypothesize that promoting this phenotype within the post-injured cord microenvironment may provide beneficial effects for mitigating tissue damage. As a proof of concept, we propose the use of nanoparticles incorporating the carbohydrate antigen, galactose-α-1,3-galactose (α-gal epitope) as an immunomodulator to transition human microglia (HMC3) cells toward a pro-healing state. Quiescent HMC3 cells were acutely exposed to α-gal nanoparticles in the presence of human serum and subsequently characterized for changes in cell shape, expression of anti or pro-inflammatory markers, and secretion of phenotype-specific cytokines. HMC3 cells treated with serum activated α-gal nanoparticles exhibited rapid enlargement and shape change in addition to expressing CD68. Moreover, these activated cells showed increased expression of anti-inflammatory markers like Arginase-1 and CD206 without increasing production of pro-inflammatory cytokines TNF-α or IL-6. This study is the first to show that resting human microglia exposed to a complex of α-gal nanoparticles and anti-Gal (from human serum) can be activated and polarized toward a putative M2 state. The data suggests that α-gal nanoparticles may have therapeutic relevance to the CNS microenvironment, in both recruiting and polarizing macrophages/microglia at the application site. The immunomodulatory activity of these α-gal nanoparticles post-SCI is further described in the companion work (Part II). Resting microglia subjected to α-gal nanoparticle treatment in the presence of anti-Gal (found in serum) become activated and exhibit pro-healing phenotypic markers (Arginase-1, CD206) and secrete VEGF. Expression of pro-inflammatory markers (IL-6, TNF-α) was concomitantly reduced.


Comparison of cytogenetics and molecular karyotyping for chromosome testing of miscarriage specimens.
To compare chromosome testing of miscarriage specimens between traditional cytogenetic analysis and molecular karyotyping using single nucleotide polymorphism microarrays (SNP) and array comparative genomic hybridization (aCGH). Prospective blinded cohort study. University-based practice. Women undergoing dilation and curettage for first-trimester miscarriage between March 2014 and December 2015. None. Chromosome analysis from chorionic villi separated equally and submitted for cytogenetics, SNP microarray, and aCGH testing. Sixty samples were analyzed, of which 47 (78%) were chromosomally abnormal. A correct call was defined when a result was concordant with at least one other testing platform. The correct call rate was 85%, 93%, and 85% using cytogenetics, SNP array, and aCGH, respectively. We found a 33% overall discordance rate between results. Discordances were due to maternal cell contamination, balanced chromosome rearrangements, polyploidy, and placental mosaicism. Mosaicism was detected in 18% of all samples. Growth failure occurred in four samples sent to cytogenetics, of which three were chromosomally abnormal by molecular testing. This study demonstrates the many technical limitations of the three testing modalities. Our rates of maternal cell contamination were low, but it is important to note that this is a commonly reported limitation of cytogenetics. Given the similar overall performance of the three testing modalities, providers may choose a method based on individual availability and consideration of limitations as it applies to each clinical scenario. The unexpected high rate of placental mosaicism warrants further investigation.


The importance of inhibition of a catabolic pathway of methotrexate metabolism in its efficacy for rheumatoid arthritis.
Methotrexate (MTX), an antifolate, is the anchor drug for the treatment of rheumatoid arthritis (RA). It is inexpensive, effective, and generally safe. When clinical response is inadequate, biological therapies are commonly used in combination with MTX. However, biological agents have safety concerns (i.e. infections, malignancy) and the addition of a biologic agent is expensive, making strategies to improve MTX efficacy important. Inhibition of pathways of folate metabolism involving purine metabolism by MTX, have been traditionally emphasized as important in MTX efficacy. However, inhibition MTX catabolism may also be important. MTX is irreversibly hydroxylated to form 7-hydroxy methotrexate (7-OH-MTX) by aldehyde oxidase (EC 126.96.36.199) (AOX). Catabolism of MTX to 7-OH-MTX is the first metabolic process imposed on an oral dose of MTX and will alter subsequent interactions of MTX with other enzymes. 7-OH-MTX is less potent than MTX in the treatment of rat adjuvant arthritis. RA patients with a low capacity to catabolize MTX to 7-OH-MTX do better clinically than individuals who are rapid formers of 7-OH-MTX. Therefore, altering the catabolism of MTX may be an innovative way to improve MTX efficacy. Raloxifene is a FDA-approved therapy for postmenopausal osteoporosis and for the reduction of invasive breast cancers but has no known activity in RA. Raloxifene is a potent inhibitor of human liver AOX. Postmenopausal women with RA frequently have low bone mineral density and would be candidates for raloxifene and MTX combination therapy. The effect of raloxifene on MTX metabolism has never been studied. Our hypothesis is that in postmenopausal women with RA and osteoporosis treated with MTX and raloxifene, the inhibition of AOX with resultant decreased formation of 7-OH MTX; will increase MTX levels and improve MTX efficacy. This hypothesis could be studied in an open-label, proof of concept clinical study in individuals before and after the addition of raloxifene. Red blood cell MTX and 7-OH-MTX levels and RA disease activity (DAS28) would be measured. In possible future studies, there are dietary substances, as supplements, (e.g. epigallocatechin gallate in green tea and resveratrol) which inhibit human liver AOX which could be evaluated.


Clinical features, outcomes, and HLA risk factors associated with nitrofurantoin-induced liver injury.
Nitrofurantoin (NTF) is widely used for the treatment (short-term) and prevention (long-term) of urinary tract infections. We aimed to describe the clinical characteristics, outcomes, and HLA risk factors for NTF-induced liver injury (NTF-DILI) among individuals enrolled in the Drug Induced Liver Injury Network (DILIN). Seventy-eight individuals with definite, highly likely, or probable NTF-DILI were enrolled into DILIN studies between 2004-2020. HLA alleles were compared between NTF-DILI and three control groups: population (n = 14,001), idiopathic autoimmune hepatitis (n = 231), and non-NTF DILI (n = 661). Liver injury was hepatocellular in 69% and icteric in 55%. AST > ALT was more common in the 44 long-exposure (≥1 year) NTF-DILI cases than in the 18 short (≤7 days) and 16 intermediate (>7 to <365 days) exposure cases (73% vs. 33% vs. 50%, respectively, p = 0.018), as was ANA or SMA positivity (91% vs. 44% vs. 50%, respectively, p <0.001), and corticosteroid use (61% vs. 27% vs. 44%, respectively, p = 0.06). In long-term NTF-DILI, bridging fibrosis, nodularity or cirrhosis, or clinical and imaging evidence for cirrhosis were present in 38%, with massive or sub-massive necrosis in 20%. No one in the short-term exposure group died or underwent transplantation, whereas 7 (12%) patients from the other groups died or underwent transplantation. After covariate adjustments, HLA-DRB1∗11:04 was significantly more frequent in NTF-DILI compared to population controls (odds ratio [OR] 4.29, p = 1.15 × 10-4), idiopathic autoimmune hepatitis (OR 11.77, p = 7.76 × 10-5), and non-NTF DILI (OR 3.34, p = 0.003). NTF-DILI can result in parenchymal necrosis, bridging fibrosis, cirrhosis, and death or liver transplantation, especially with long-term exposure, and is associated with HLA-DRB1∗11:04. To mitigate against serious liver injury associated with NTF, regulators should revise the prescribing information and consider other mitigation strategies. Nitrofurantoin is a recognized cause of drug-induced liver injury (DILI). In this study consisting of a large cohort of well-phenotyped individuals with nitrofurantoin-induced liver injury, two distinct patterns of liver injury were identified: liver injury associated with short-term exposure, which is generally self-limiting, and liver injury associated with long-term exposure, which can lead to advanced fibrosis, cirrhosis and liver failure. HLA DRB1∗11:04 is a risk factor for liver injury due to long-term nitrofurantoin exposure. Our findings are important for regulators as well as physicians prescribing and pharmacists dispensing nitrofurantoin.


Triple Positive Antiphospholipid Antibody Syndrome in Pregnancy with High Frequency Plasma Exchange: A Case Report.
Triple antibody positive antiphospholipid syndrome during pregnancy carries a poor prognosis. The placental vasculature is particularly vulnerable to these antibodies resulting in a marked increased risk of fetal growth restriction, placental infarction, abruption, stillbirth, and preterm severe preeclampsia. We report a case of a primigravida with triple antibody positive antiphospholipid syndrome that demonstrated placental insufficiency and fetal compromise at a previable gestation. The patient underwent plasma exchange every 48 h for 11 weeks resulting in delivery of a viable infant. Placental blood flow was improved after complete absence of end-diastolic flow in the fetal umbilical artery. Scheduled plasmapheresis every 48 h can be considered in select cases of antiphospholipid antibody syndrome.


Gender commonalities and differences in risk and protective factors of suicidal thoughts and behaviors: A cross-sectional study of Spanish university students.
To assess gender differences in the association between risk/protective factors and suicidal thoughts and behaviors (STB); and whether there is any gender-interaction with those factors and STB; among Spanish university students. Data from baseline online survey of UNIVERSAL project, a multicenter, observational study of first-year Spanish university students (18-24 years). We assessed STB; lifetime and 12-month negative life-events and family adversities; mental disorders; personal and community factors. Gender-specific regression models and gender-interactions were also analyzed. We included 2,105 students, 55.4% women. Twelve-month prevalence of suicidal ideation (SI) was 10%, plans 5.7%, attempts 0.6%. Statistically significant gender-interactions were found for lifetime anxiety disorder, hopelessness, violence between parents, chronic health conditions and family support. Lifetime mood disorder was a common risk factor of SI for both genders (Females: OR= 5.5; 95%CI 3.3-9.3; Males: OR= 4.4; 95%CI 2.0-9.7). For females, exposure to violence between parents (OR= 3.5; 95%CI 1.7-7.2), anxiety disorder (OR= 2.7; 95%CI 1.6-4.6), and alcohol/substance disorder (OR= 2.1; 95%CI 1.1-4.3); and for males, physical childhood maltreatment (OR= 3.6; 95%CI 1.4-9.2), deceased parents (OR= 4.6; 95%CI 1.2-17.7), and hopelessness (OR= 7.7; 95%CI 2.8-21.2), increased SI risk. Family support (OR= 0.5; 95%CI 0.2-0.9) and peers/others support (OR= 0.4; 95%CI 0.2-0.8) were associated to a lower SI risk only among females. Only mood disorder was a common risk factor of SI for both genders, whereas important gender-differences were observed regarding the other factors assessed. The protective effect from family and peers/others support was observed only among females. Further research assessing underlying mechanisms and pathways of gender-differences is needed.


Osmotic and curvature stress affect PEG-induced fusion of lipid vesicles but not mixing of their lipids.
Poly (ethylene glycol) (PEG) in the external environment of membrane vesicles creates osmotic imbalance that leads to mechanical stress in membranes and may induce local membrane curvature. To determine the relative importance of membrane stress and curvature in promoting fusion, we monitored contents mixing (CM) and lipid mixing (LM) between different sized vesicles under a variety of osmotic conditions. CM between highly curved vesicles (SUV, 26 nm diameter) was up to 10 times greater than between less curved vesicles (LUV, 120 nm diameter) after 5 min incubation at a low PEG concentration (<10 wt%), whereas LM was only approximately 30% higher. Cryo-electron microscopy showed that PEG at 10 wt% did not create high curvature contacts between membranes in LUV aggregates. A negative osmotic gradient (-300 mOs/kg, hypotonic inside) increased CM two- to threefold for both types of vesicles, but did not affect LM. A positive gradient (+220 mOs/kg, hypertonic inside) nearly eliminated CM and had no effect on LM. Hexadecane added to vesicles had no effect on LM but enhanced CM and reduced the inhibitory effect on CM of a positive osmotic gradient, but had little influence on results obtained under a negative osmotic gradient. We conclude that the ability of closely juxtaposed bilayers to form an initial intermediate ("stalk") as soon as they come into close contact was not influenced by osmotic stress or membrane curvature, although pore formation was critically dependent on these stresses. The results also suggest that hexadecane affects the same part of the fusion process as osmotic stress. We interpret this result to suggest that both a negative osmotic gradient and hexadecane reduce the unfavorable free energy of hydrophobic interstices associated with the intermediates of the fusion process.


Gene reprogramming in exercise-induced cardiac hypertrophy in swine: A transcriptional genomics approach.
Cardiac hypertrophy of the left ventricle (LV) in response to dynamic exercise-training (EX) is a beneficial adaptation to increased workload, and is thought to result from genetic reprogramming. We aimed to determine which transcription factors (TFs) are involved in this genetic reprogramming of the LV in swine induced by exercise-training. Swine underwent 3-6 weeks of dynamic EX, resulting in a 16% increase of LV weight/body weight ratio compared to sedentary animals (P=0.03). Hemodynamic analysis showed an increased stroke volume index (stroke volume/body weight +35%; P=0.02). Microarray-analysis of LV tissue identified 339 upregulated and 408 downregulated genes (false discovery rate<0.05). Of the human homologues of the differentially expressed genes, promoter regions were searched for TF consensus binding sites (TFBSs). For upregulated and downregulated genes, 17 and 24 TFBSs were overrepresented by >1.5-fold (P<0.01), respectively. In DNA-binding assays, using LV nuclear protein extracts and protein/DNA array, signal intensity changes >2-fold were observed for 23 TF-specific DNA probes. Matching results in TFBS and protein/DNA array analyses were obtained for transcription factors YY1 (Yin Yang 1), PAX6 (paired box 6) and GR (glucocorticoid receptor). Notably, PAX6 and GR show lower signals in TFBS and protein/DNA array analyses upon exercise-training, whereas we previously showed higher signals for these factors in the remodeled LV of swine post-myocardial infarction (MI). In conclusion, we have identified transcription factors that may drive the genetic reprogramming underlying exercise-training induced LV hypertrophy in swine. PAX6 and GR are among the transcription factors that are oppositely regulated in LV hypertrophy after exercise-training and MI. These proteins may be at the base of the differences between pathological and physiological hypertrophy.


Power losses reduction in a variable linear power supply using the LM317 voltage regulator.
In this work, the design and development of a new variable linear power supply, using the LM317 regulator, is proposed. The originality of this power supply is related with the control of the rectifier circuit, which is based on a reference of voltage, superimposed on the output voltage. This reference is used in the control strategy to maintain a constant voltage between the input and the output voltages of the LM317 regulator. Due to this strategy, the heating losses are greatly reduced, allowing to increase the efficiency of the regulator to about 90%, and to reduce the requirements of the cooling system. Moreover, drawbacks of conventional power supplies are mitigated, where the developed variable linear power supply delivers a current of 3 A and a variable output voltage, from 1.2 V to 30 V. The LM317 regulator was modeled by its thermal equivalent structure associated with a heatsink to study the heat transfer problem. The modeling was performed on the Matlab Simulink software, and the theoretical results were validated by a set of experimental tests using the LM317 regulator.


Chemotaxis in the green flagellate alga Chlamydomonas.
Behavior of the green flagellate alga Chlamydomonas changes in response to a number of chemical stimuli. Specific sensitivity of the cells to different substances might appear only at certain stages of the life cycle. The heterogamous species C. allensworthii demonstrates chemotaxis of male gametes towards pheromones excreted by female gametes. In C. reinhardtii chemotaxis towards tryptone occurs only in gametes, whereas chemotaxis towards ammonium, on the contrary, only in vegetative cells. Chemotaxis to different chemical stimuli might involve different mechanisms of reception and signal transduction, elucidation of which has only recently begun. Indirect evidences show that the cells likely respond to tryptone with changes in the membrane electrical conductance. The recently completed project of sequencing the whole nuclear genome of C. reinhardtii provides the basis for future identification of molecular elements of the chemosensory cascade in this alga.


Early stages in RecA protein-catalyzed pairing. Analysis of coaggregate formation and non-homologous DNA contacts.
RecA protein will catalyze the in vitro pairing of homologous DNA molecules. To further explore the events involved in the search for homology, we have applied a nitrocellulose filter binding assay to follow pairing, and a sedimentation assay to follow the generation of aggregates (termed coaggregates) formed between RecA-complexed single-stranded (ss) DNA and double stranded (ds) DNA. Electron microscopy (EM) was used to visualize the structures involved. RecA protein promoted the pairing of circular M13 ssDNA and linear M13mp7 dsDNA efficiently in the absence of coaggregates. Indeed, pairing of homologous ss- and dsDNAs involved coaggregate formation only if the dsDNA was circular. For DNAs containing only a few hundred base-pairs of homology, for example pUC7 dsDNA and M13mp7 ssDNA, pairing and joint formation was observed if the dsDNA was superhelical but not if it was topologically relaxed or linear with the homology internal to an end of the dsDNA. The effect of non-covalently attached heterologous dsDNA on the RecA-promoted joining of M13 ssDNA and linear M13mp7 dsDNA (with non-M13 sequences at both ends) was found to depend on the topology and concentration of the heterologous DNA. A tenfold excess of superhelical pBR322 DNA strongly inhibited pairing. However, addition of relaxed or linear pBR322 DNA to the pairing reaction had little effect. As seen by EM, superhelical pBR322 DNA inhibited joint formation by excluding the homologous dsDNA form the coaggregates. EM also revealed heterologous DNA interactions presumably involved in the search for homology. Here the use of EM has provided a direct visualization of the form and architecture of coaggregates revealing a dense interweaving of presynaptic filaments and dsDNA.


Timing of meristem initiation and maintenance determines the morphology of fern gametophytes.
The alternation of generations in land plants occurs between the sporophyte phase and the gametophyte phase. The sporophytes of seed plants develop self-maintained, multicellular meristems, and these meristems determine plant architecture. The gametophytes of seed plants lack meristems and are heterotrophic. In contrast, the gametophytes of seed-free vascular plants, including ferns, are autotrophic and free-living, developing meristems to sustain their independent growth and proliferation. Compared with meristems in the sporophytes of seed plants, the cellular mechanisms underlying meristem development in fern gametophytes remain largely unknown. Here, using confocal time-lapse live imaging and computational segmentation and quantification, we determined different patterns of cell divisions associated with the initiation and proliferation of two distinct types of meristems in gametophytes of two closely related Pteridaceae ferns, Pteris vittata and Ceratopteris richardii. Our results reveal how the simple timing of a switch between two meristems has considerable consequences for the divergent gametophyte morphologies of the two ferns. They further provide evolutionary insight into the function and regulation of gametophyte meristems in seed-free vascular plants.


Determinants of cigarette/bidi smoking among youth male in rural Mymensingh of Bangladesh: A cross-sectional study.
Smoking cigarette/bidi, is a serious health threat, causes preventable premature morbidity and mortality. Higher prevalence of smoking among the youth hampers a country's development, as the youth are the main drivers of socio-economic development. An effective understanding of factors associated with youth smoking is precious to prevent youth smoking. This study aims to identify the determinants of smoking cigarette/bidi among the youth male of the rural areas of Mymensingh district in Bangladesh. The primary data from the project "Knowledge, awareness and practices among youth smokers in Trishal Upazila under Mymensingh district: A micro-survey study", funded by the Research and Extension Center, Jatiya Kabi Kazi Nazrul Islam University, Bangladesh was utilized in the current study. The data consists of 385 youth males aged 15-24 years who were interviewed face-to-face from the rural areas of Mymensingh district in Bangladesh. Univariate distribution, chi-square tests, and binary logistic regression model were employed to identify the factors associated with smoking cigarette/bidi among the youth male. The prevalence of smoking cigarette/bidi among the youth male is 40.3% [95% CI: 35.0%-45.0%]. Age, occupation, monthly income, family's monthly income, cigarette/bidi smoking status of father, brother and close friends, and knowledge about harmfulness of smoking are revealed as the determinants of cigarette/bidi smoking. For instance, the odds of being smoker increases with the increase in age (Odds ratio [OR]: 1.33 [1.17-1.51]). Business owner is less likely (OR: 0.15 [0.03-0.68]) to smoke than the day labourer. Having smoker fathers (OR: 2.51 [1.39-4.53]), smoker brothers (OR: 2.88 [1.39-5.96]), smoker friends (OR: 9.85 [5.85-1.27]) are significantly associated with smoking cigarette/bidi. As the first study, it provides the determinants of cigarette/bidi smoking among youth male of the rural areas of Mymensingh district in Bangladesh. Relevant authorities are suggested to consider the study's findings and recommendations to revise the existing smoking policies so that smoking among youth can be prevented for future development of the country.


Planning the analysis of a breast cancer prevention trial.
The analysis of cancer prevention trials necessitates specialized procedures. Differences in the analysis plan between cancer prevention and therapy trials are emphasized. Discussion is focused upon (a) how trial conduct influences the analysis, (b) how noncompliance affects the analysis and the considerations this raises during the design and conduct of the trial, (c) how delays in the effect of the intervention impinges upon the analysis, and (d) statistical methods available to carry out the analysis. The analysis of a cancer prevention trial represents a final step in the evaluation of the study intervention and requires an adaptive planning procedure.


Molecular analysis of a baculovirus regulatory gene.
To better understand the structure and function of a baculovirus regulatory gene, the nucleotide sequence of IE-N expressed by Autographa californica nuclear polyhedrosis virus was determined. The 2.0-kb PstI-EcoRV restriction fragment (97.5 to 98.9 mu) encodes the upstream regulatory sequences, open reading frame, and downstream sequences of the immediate early IE-N gene. Using a convenient restriction site, the 285-bp promoter of IE-N was divided into two functional regions as defined by transient expression assays of mutant sequences. The sequences of IE-N from -1 to -45 nt encoded a minimal promoter capable of directing low levels of transcription. The minimal promoter was fully responsive to positive regulation by IE-N. The upstream region from -46 to -285 nt contains two direct repeats which increased levels of IE-N gene expression. Computer-assisted translation of the IE-N sequence indicates that this fragment of DNA encodes a single long open reading frame with a predicted molecular weight of 47,000. The amino acid sequence of the predicted protein exhibits three motifs common to transcriptional regulators: a serine-threonine rich region, a proline-rich region, and a polyglutamine tract. IE-N autoregulates its own expression and stimulates both IE-1 and IE-0 in transient assays. The stimulation of IE-1 may account for the augmenting activity of IE-N in the IE-1-mediated trans-activation of the 39K promoter.


Cloning and functional identification of delta5 fatty acid desaturase gene and its 5'-upstream region from marine fungus Thraustochytrium sp. FJN-10.
A gene encoding delta5 fatty acid desaturase (fad5) was cloned from marine fungus Thraustochytrium sp. FJN-10, a species capable of producing docosahexaenoic acid. The open reading frame of fad5 was 1,320 bp and encoded a protein comprising 439 amino acids. Expression of the fad5 in Saccharomyces cerevisiae INVSC1 revealed that FAD5 is able to introduce a double bond at position 5 of the dihomo-γ-linolenic acid (20:3 Δ(8,11,14)), resulting in arachidonic acid (20:4 Δ(5,8,11,14)) with a conversion rate of 56.40% which is the highest among engineering yeasts reported so far. The 5'-upstream region of fad5 was cloned by LA-PCR and analyzed. Phylogenetic analysis of this sequence with the 5'-upstream region of other delta5 desaturases showed that the 5'-upstream region of fad5 from Thraustochytrium share the smallest evolution distance with human and rhesus. Computational analysis of the nucleotide sequence of the 5'-upstream region of fad5 has revealed several basic transcriptional elements including five TATA boxes, three CCAAT boxes, 12 GC boxes, and several putative target-binding sites for transcription factors such as HSF, CAP, and ADR1. Preliminary functional analysis of this promoter in S. cerevisiae shows that the 5'-upstream region of fad5 could drive the expression of green fluorescent protein.


Immuno-electrophysiology on Neuromuscular Junctions of Drosophila Third Instar Larva.
Alterations in synaptic transmission are critical early events in neuromuscular disorders. However, reliable methodologies to analyze the functional organization of the neuromuscular synapses are still needed. This manuscript provides a detailed protocol to analyze the molecular assembly of the neuromuscular synapses through immune-electrophysiology in Drosophila melanogaster. This technique allows the quantification of the molecular behavior of the neuromuscular synapses by correlating the structural configuration of the synaptic boutons with their electrical activity.


Effect of Team Health Education on Radiodermatitis in Patients with Head and Neck Tumor Radiotherapy Under the Joint Committee International Standards.
This study aimed to investigate the impacts of team health education on radiodermatitis in patients undergoing head and neck radiotherapy. A total of 118 patients undergoing radiotherapy at the Oncology Department of Qingdao Municipal Hospital under the Joint Committee International (JCI) accreditation standards of medical and health institutions were divided into two groups according to the order of the admission: the intervention group (n = 66) and the control group (n = 52). The patients in the control group were given routine nursing, while those in the intervention group received team health education based on the control group. The incidence and satisfaction of radiodermatitis were observed and compared between the groups, and the EORTC QLQ-C30 and General Quality of Life Inventory-74 were used to evaluate the patients' quality of life when after radiotherapy and when after 6 months post the radiotherapy, respectively. The incidence of radiodermatitis was 100% in both groups, and the difference in the grade of radiodermatitis and quality of life was significant (P < .05) between them. Team health education under the JCI standards team can reduce the degree of skin injury due to radiodermatitis and improve the quality of life.


Exercise-induced bronchoconstriction. Seasonal variation in children with asthma and in those with rhinitis.
Standardized exercise challenge tests, symptom scores and whole-blood eosinophil and basophil counts were made before and during the pollen season in 32 children suffering from hay fever (n = 16) or hay fever and asthma (n = 16). All participants developed rhinitis symptoms during the season. The hay fever group showed in addition a significant seasonal increase in cough score (but in no other asthma symptom) and in circulating eosinophils (P less than 0.01); mean exercise-induced bronchoconstriction (EIB) did not change despite a slight increase in a few subjects. The asthma group showed seasonal increases in EIB (P less than 0.001), asthma symptom score (P less than 0.002), and total eosinophil count (P less than 0.001). The increase in the latter was significantly higher (P less than 0.05) than that in the hay fever group. The relative basophil count remained unchanged in both groups. In conclusion, the hay fever group and the asthma group could be clearly distinguished with respect to EIB during natural pollen exposure. The significantly higher increases in EIB and circulating eosinophils observed in the asthma group might possibly be due to greater pollen antigen sensitivity in the asthmatics.


A promising new tool for fault diagnosis of railway wheelset bearings: SSO-based Kurtogram.
A promising method is proposed systematically to select an accurate resonance frequency band and separate refined resonance response from periodic excitation in this study. This work expanded the short-time Fourier transform (STFT)- and wavelet transform (WT)-based Kurtograms and developed a hybrid signal separation operator (SSO)-spectral kurtosis computational scheme to implement Kurtogram by introducing the SSO method-SSO-based Kurtogram. The ability to accurately extract the refined resonance frequency band of SSO greatly improves its adaptivity for engineering applications. The effectiveness of the SSO-based Kurtogram is studied by using a bearing fault simulation signal, and the influence of window function on the detection effect of the proposed method is explored. Furthermore the validity of the SSO-based Kurtogram for bearing fault detection is verified by a set of railway wheelset-bearing experiments on the wheelset running-in testbed bench. Experimental results show that the SSO-based Kurtogram performs highly in detecting various kinds of single and compound faults of bearings. Compared with the WT- and STFT-based Kurtogram, the proposed method has obvious advantages in terms of effectiveness and visual inspection ability. In engineering practice, a railway wheelset-bearing-fault experiment on an in-service high-speed train in the real world is taken as a case study, which makes the verification of SSO-based Kurtogram more convincing and demonstrates the practical engineering value of the proposed method. The results show that in case of equal effectiveness, SSO-based Kurtogram has an absolute advantage in the visual inspection ability, embodied in eliminating other vibrations unrelated to the target fault and making the fault feature frequency and its harmonics remarkable.


Promotion of Proton Conductivity by Encapsulation of Metal-Organic Polyhedra in Metal-Organic Frameworks.
A Zr-based metal-organic polyhedron (MOP) was self-assembled in a porous MOF host, DUT-68, successfully to synthesize MOP-1@DUT-68. The MOP guest (MOP-1) has a diameter of about 20 Å, larger than that of the square windows (pore sizes of ∼14 Å) of DUT-68 but smaller than that of the rhombicuboctahedral cage (27.7 Å), which means that the migration and leaching of MOP-1 could be effectively prohibited if MOP-1 is encapsulated in the MOF's cavities. The proton conductivity of MOP-1@DUT-68 is 1.14×10-3 S cm-1 (at 80 °C under 98 % relative humidity), which is three orders of magnitude higher than that of DUT-68. Compared with MOP-1⊂DUT-68, which was synthesized by impregnation, MOP-1@DUT-68 is more prone to form faster proton-conduction pathways and thus provides higher proton conductivity.


Clinico-Pathological Features Influencing the Prognostic Role of Body Mass Index in Patients With Advanced Renal Cell Carcinoma Treated by Immuno-Oncology Combinations (ARON-1).
Obesity has been associated with improved response to immunotherapy in cancer patients. We investigated the role of body mass index (BMI) in patients from the ARON-1 study (NCT05287464) treated by dual immuno-oncology agents (IO+IO) or a combination of immuno-oncology drug and a tyrosine kinase inhibitors (TKI) as first-line therapy for metastatic renal cell carcinoma (mRCC). Medical records of patients with documented mRCC treated by immuno-oncology combinations were reviewed at 47 institutions from 16 countries. Patients were assessed for overall survival (OS), progression-free survival (OS), and overall clinical benefit (OCB), defined as the sum of the rate of partial/complete responses and stable disease. Univariate and multivariate analyses were used to explore the association of variables of interest with survival. A total of 675 patients were included; BMI was >25 kg/m2 in 345 patients (51%) and was associated with improved OS (55.7 vs. 28.4 months, P < .001). The OCB of patients with BMI >25 kg/m2 versus those with BMI ≤25 kg/m2 was significantly higher only in patients with nonclear cell histology (81% vs. 65%, P = .011), and patients with liver metastases (76% vs. 58%, P = .007), Neutrophil to lymphocyte ratio >4 (77% vs 62%, P = .022) or treated by nivolumab plus ipilimumab (77% vs. 64%, P = .044). In the BMI ≤25 kg/m2 subgroup, significant differences were found between patients with NLR >4 versus ≤4 (62% vs. 82%, P = .002) and patients treated by IO+IO versus IO+TKIs combinations (64% vs. 83%, P = .002). Our study suggests that the prognostic significance and the association of BMI with treatment outcome varies across clinico-pathological mRCC subgroups.


Non-invasively quantified changes in left ventricular activation predict outcomes in patients undergoing cardiac resynchronization therapy.
Changes in left ventricular (LV) activation after cardiac resynchronization therapy (CRT) influence survival but are difficult to quantify noninvasively. We studied 527 CRT patients to assess whether noninvasive quantification of changes in LV activation, defined by change (Δ) in QRS area (QRSA), can predict outcomes after CRT. The study outcome was time until LV assist device(LVAD), cardiac transplant, or death. The three-dimensional QRSA was measured from clinical 12 lead ECGs which were transformed into vectorcardiograms using the Kors method. QRSA was calculated as (QRSx2 + QRSy2 + QRSz2 )1/2 ; ΔQRSA was calculated as post-QRSA minus pre-QRSA, where a negative value represents a reduction in LV activation delay. Kaplan-Meier plots and multivariable Cox proportional hazards models were used to relate ΔQRSA area with outcomes after stratifying the population into quartiles of ΔQRSA. The median baseline QRSA of 93.6 µVs decreased to 59.7 µVs after CRT. Progressive reductions in QRSA with CRT were associated with a lower rate of LVAD, transplant, or death across patient quartiles (P < .001). In Cox regression analyses, ΔQRSA was associated with outcomes independent of QRS morphology and other clinical variables (Q1[greatest decrease] vs Q4[smallest change=reference], HR 0.45, CI, 0.30-0.70, P < .001). There was no interaction between ΔQRSA and QRS morphology. CRT induced ΔQRSA was associated with clinically meaningful changes in event-free survival. ΔQRSA may be a novel target to guide lead implantation and device optimization.


Low ejection fraction predicts shortened survival in patients undergoing infrainguinal arterial reconstruction.
With the advent of endovascular therapy for lower extremity ischemia it is important to better determine what factors may affect the outcome. The goal of the present study was to evaluate whether ejection fraction (EF) is predictive of outcome in infrainguinal arterial reconstruction. We retrospectively reviewed 736 patients undergoing 897 infrainguinal arterial reconstructions from July 1999 to February 2002. Patients were divided into two groups: group I contained 54 patients with an EF<35% and group II had 216 patients with an EF > or =35%. The outcome evaluated was major adverse clinical events (MACEs), defined as postoperative myocardial infarction (MI), arrhythmia, congestive heart failure (CHF), and perioperative mortality. Major adverse clinical events occurred in 20.3% of patients (11/54) in group I and 10.6% patients (23/216) in group II (p = 0.068). Group I had a trend toward a greater incidence of MACEs compared to group II. Two-year survival for group I was 61.7%, whereas survival for group II was 78.4% (p = 0.0085). Low EF predicts a significantly shortened 2-year survival after infrainguinal arterial reconstruction and a trend toward increased perioperative complications. This is another factor to be considered in choosing open versus endovascular options.


Toxicodynamics of low level toxicant interactions of biological significance: inhibition of tissue repair.
Because of the complexity of studying the toxicological effects of mixtures of chemicals, much of the mechanistic information has become available through work with binary mixtures of toxic chemicals. Mechanisms derived from studies employing chemicals at individually nontoxic doses are more useful than the mechanisms of interactive toxicity at high doses from the perspective of environmental and public health. Several examples of chemical combinations and interactive toxicity at low doses are now available. Chlordecone-potentiated halomethane hepatotoxicity, where suppression of cell division and tissue repair response permits very high amplification of CCl4 injury culminating in animal mortality, is one such model. Phenobarbital-potentiated CCl4 injury does not lead to animal mortality in spite of much higher liver injury in comparison to the chlordecone+CCl4 model. Much higher stimulation of tissue repair allows the animals to survive despite higher liver injury. Similar interactions have been reported between alcohols and halomethane toxicants. These and other studies have revealed that infliction of toxicant-induced injury is accompanied by a parallel but opposing tissue repair stimulation response which allows the animals to overcome that injury up to a threshold dose. Beyond this threshold, tissue repair response is both diminished and delayed allowing unrestrained progression of injury. Large doses of chemicals can be predictably lethal owing to these two latter effects on tissue repair. Dose-response paradigms in which tissue repair response is measured as a parallel but opposing effect to toxic injury might be useful in more precise prediction of the ultimate outcome of toxic injury in risk assessment. Autoprotection experiments with CCl4, thioacetamide, 2-butoxyethanol and related chemicals as well as heteroprotection against acetaminophen-induced lethality with thioacetamide are examples where tissue repair stimulation has been shown to rescue the animals from massive and normally lethal liver injury. The concept of toxicodynamic interaction between inflicted injury and stimulated tissue repair offers mechanistic opportunity to fine-tune other aspects of human health risk assessment procedure. Tissue repair mechanisms may also offer a mechanistic basis to explain species and strain differences as well as to more accurately assess inter-individual differences in human sensitivity to toxic chemicals. Because tissue repair is affected by nutritional status, assessment of risk from exposure to chemicals without attention to nutritional status may be misleading. Finally, the concept of using maximum tolerated doses (MTDs) in long-term toxicity studies such as cancer bioassays may need to be re-examined. MTDs might be predictably expected to maximally stimulate cell division and it is known that increased cell division is likely to lead to increased number of errors in DNA replication thereby predisposing these animals to cancer. It is clear that detailed studies of toxicodynamic interaction between tissue injury and stimulated tissue repair are likely to yield significant dividends in fine-tuning risk assessment.


PET-positive fibrous dysplasia--a potentially misleading incidental finding in a patient with intimal sarcoma of the pulmonary artery.
Benign bone tumors can show an increased FDG uptake in FDG-PET/CT investigations. In the presented case, an incidentally detected PET-positive asymptomatic fibrous dysplasia was initially misinterpreted as a metastasis in a patient with intimal sarcoma of the pulmonary artery.


Referral guidelines for medical imaging in children: an ESR-EuroSafe Imaging survey on availability, awareness and use in clinical practice among European radiologists.
Justification of medical exposures from medical imaging is fundamental to radiation protection. Referral guidelines are intended to help physicians decide when an imaging study is justified. For two decades, referral guidelines have been a legally binding requirement for European Union member states. Recently, the European Society of Radiology (ESR) developed iGuide tool, which provides evidence-based referral guidance for imaging inclusive of children. The aim of this survey was to assess the availability, use and familiarity of referral guidelines for medical imaging in children and knowledge about the availability of ESR iGuide among ESR member radiologists. Over a 2-month period (15 September-15 November 2019), 33,257 ESR member radiologists were invited to respond to an anonymised web-based questionnaire, which consisted of 12 multiple-choice questions. In total, 2067/33,257 responses (6.3%) were received from 52 countries. A total of 1068 out of 2067 (51.7%) respondents were aware that imaging referral guidelines are a legal requirement. One thousand five (48.6%) of all respondents did not know whether dedicated guidelines for imaging in children were available, and only 653 (31.2%) were aware of the mainstays of the available guidelines. Similarly, just 746 (36.1%) of all respondents were aware of ESR iGuide availability and features. The information gathered confirms that effective and widespread adoption of imaging referral guidelines is lacking, especially in children. Further work is required to improve uptake and awareness. • Justification of medical exposures is fundamental to radiation protection and evidence-based referral guidelines are crucial for practical implementation of this principle. • About half of survey respondents are aware that the availability of imaging referral guidelines is a legal requirement, despite this being mandated since 1997. • The information gathered from this survey confirms that, especially in children, an effective and widespread adoption of imaging referral guidelines is lacking.


Patient and Family Perspectives on Early Mobilization in Acute Cardiac Care.
Emerging evidence indicates that engaging family members in early mobilization may benefit both patients and family members. However, little is known about the effect of patient and family-member experience and perspectives on mobilization in acute cardiac care. Our goal was to assess the perspectives and experience of patients and their family members regarding early mobilization in acute cardiac care, to better understand patient-related barriers to mobilization and assist in the development of mobilization strategies that increase family-member engagement in care. Patient and family-member surveys were developed to assess attitudes and knowledge about mobilization, family-members' roles in providing care, and mobilization care the patients received. Surveys were distributed to patients and their family members over a 4-month period. A total of 101 participants completed the survey (patients, n = 78; family members, n = 23). Most patients (n = 54; 69.2%) agreed or strongly agreed that early mobilization should be routinely performed. Of 72 patients who underwent early mobilization, 60 (83.3%) felt that mobilization helped their recovery. The majority of family members were interested in being involved with mobilization (n = 19; 82.6%). One quarter of family members felt that mobilizing their relatives too soon after admission was potentially dangerous (n = 6; 26.1%). Most patients wish to be mobilized early after admission, and family members want to participate in mobilization efforts. These findings should inform efforts to overcome patient- and family-related barriers to mobilization.


Drug-eluting bead transarterial chemoembolization (TACE) exhibits superior efficacy and equal tolerance to conventional TACE in hepatocellular carcinoma patients with conventional TACE history.
Multiple conventional transarterial chemoembolization (cTACE) procedures would cause treatment resistance in hepatocellular carcinoma (HCC) patients, whether drug-eluting bead transarterial chemoembolization (DEB-TACE) would resolve this issue is a necessary topic. Thus, this study aimed to compare the efficacy and safety between DEB-TACE and cTACE in HCC patients with cTACE treatment history. Totally, 134 HCC patients with cTACE treatment history were retrospectively reviewed. They were categorized into DEB-TACE group (N = 70) and cTACE group (N = 64) based on the current treatment they received. After 1-month treatment, DEB-TACE group exhibited an elevated objective response rate (ORR) (71.9% vs. 47.3%, P = 0.008) while similar disease control rate (DCR) (93.0% vs. 81.8%, P = 0.074) compared to cTACE group. Besides, after 3-month treatment, DEB-TACE group also displayed higher ORR (68.4% vs. 44.1%, P = 0.038) and DCR (81.6% vs. 58.8%, P = 0.034) compared to cTACE group. Furthermore, the median progression-free survival (PFS) (11.5 months vs. 6.5 months P = 0.014) and overall survival (OS) (18.5 months vs. 13.0 months, P = 0.025) were longer in DEB-TACE group compared to cTACE group. Moreover, DEB-TACE (vs. cTACE) independently correlated with prolonged PFS (P = 0.021) and OS (P = 0.017) after adjustment by multivariate Cox's regression. Besides, most of liver function indexes were similar before and after treatment between these two groups. Also, the commonly observed adverse events were pain, fever, nausea/vomiting and blood pressure elevation with similar incidence between these two groups (all P > 0.050). DEB-TACE exhibits superiority over cTACE in HCC patients with cTACE treatment history.


Ingol, ent-atisane, and stachane-type diterpenoids from Euphorbia deightonii with multidrug resistance reversing activity.
Nine previously undescribed ingol-type diterpenoid polyesters with eighteen known ingol esters, two ent-atisane, and one stachane diterpenoid were isolated from the methanol extract of Euphorbia deightonii Croizat. The structures were established by extensive spectroscopic analysis involving 1D (1H, 13C J-modulation) and 2D NMR experiments, HRESIMS measurements, and the comparison of the spectroscopic data with reported literature values. The cytotoxic concentrations of 13 isolated compounds were determined, and the compounds were investigated for multidrug resistance modulating activity on an L5178 mouse lymphoma cell line using a rhodamin 123 accumulation assay. Six ingol esters demonstrated the significant inhibition of P-glycoprotein, while the two ent-atisane diterpenoids were found to be inactive. The measured activities allowed to establish some structure-activity relationships. Notably, lower and higher-type diterpenoids simultaneously occurred in E. deightonii.


Characteristics of diarrheagenic Escherichia coli among patients with acute diarrhea in China, 2009‒2018.
Objectives To investigate the epidemiological features of diarrheagenic Escherichia coli (DEC) in patients with acute diarrhea in China. Methods An active sentinel surveillance was performed in all-age patients with acute diarrhea in China, 2009‒2018. DEC was isolated and identified by serological assay and PCR from stool samples. Results DEC was determined in 6.68% (6,119/91,651) of the patients, with higher positive rates among females than among males (6.97% vs. 6.46%) and among 18‒59 years patients (7.88%) than among other age groups. Five pathotypes were identified, the most prevalent was enteroaggregative E. coli (EAEC), followed by enteropathogenic E. coli (EPEC), and enterotoxigenic E. coli (ETEC). Pediatric patients <5 years had higher positive rate of EAEC (2.07%), followed by EPEC (1.81%), and enterohemorrhagic E. coli (EHEC) (0.31%), while the 18‒59 years patients had higher infection of ETEC (2.36%). ETEC and EPEC were more frequently identified in urban than rural areas, with age and gender adjusted positive rate of 1.68% vs. 1.14% respectively, and 1.77% vs. 1.55%, while EIEC and EHEC were more frequently identified in rural areas. Conclusions These findings highlight the epidemiology features of DEC and underscores the need for conducting DEC surveillance.


Prospective, randomized trial of selective proximal vagotomy with ulcer excision and partial gastrectomy with gastroduodenostomy in the treatment of corporeal gastric ulcer.
In a prospective, randomized trial, selective proximal vagotomy with complete ulcer excision was compared with partial gastrectomy with gastroduodenostomy for the treatment of primary corporeal gastric ulcer in 30 patients. The results were evaluated by clinical follow-up examinations at regular intervals, endoscopy, and blood tests. The mean follow-up period was 3 years for both operations. There was no mortality. Postoperative complications, ulcer recurrence rates, the overall clinical results (Visick classification), and blood test results were similar in the two groups. Three of 15 selective proximal vagotomy patients were classified grade IV due to recurrent ulcer (two patients) or dumping (1 patient), and 2 of 14 partial gastrectomy patients as were classified grades III (epigastric pain) and IV (recurrent ulcer). Considering the risk for late symptoms of impaired resorption and gastric cancer after partial gastrectomy, the similar results with selective proximal vagotomy and partial gastrectomy justify further trials of selective proximal vagotomy with ulcer excision for treatment of corporeal gastric ulcer.


Behavioral Approaches to Nutrition Counseling in the Primary Care Setting.
Primary care providers encounter significant time and resource constraints in their efforts to provide patients with behavioral nutrition counseling. Here, several evidence-based and low-burden strategies are identified that may be used in the primary care setting to assist patients in making dietary changes toward improved health. These strategies include brief dietary intake screening, core elements of motivational interviewing and cognitive behavioral therapy, and recommendation for normalized eating.


Aerobic exercise during pregnancy influences fetal cardiac autonomic control of heart rate and heart rate variability.
Previous studies using ultrasound technology showed that fetal heart rate (HR) may be responsive to maternal aerobic exercise. Although it is recognized that cardiac autonomic control may be influenced by the intrauterine environment, little is known about how maternal exercise affects fetal heart development. This study tested the hypothesis that regular maternal exercise throughout gestation influences fetal cardiac autonomic control of HR and heart rate variability (HRV) when compared to fetuses of non-exercising women. Magnetocardiograms (MCGs) were recorded using a dedicated fetal biomagnetometer at 28, 32 and 36 weeks gestational age (GA) from 26 regularly exercising (>30 min of aerobic exercise, 3x per week) and 35 healthy, non-exercising pregnant women. Fetal MCG was isolated and normal R-peaks were marked to derive fetal HR and HRV in the time and frequency domains. We applied a mixed-effects model to investigate the effects of exercise, GA and fetal activity state. At 36 weeks GA, during the active fetal state, fetal HR was significantly lower in the exercise group (p=<0.0006). Post-hoc comparisons showed significantly increased HRV in the exercise group during the active fetal state at 36 weeks GA for both time and frequency domain measures. These results indicate that regular maternal exercise throughout gestation results in significantly lower fetal HR and increased HRV.


An edge detection algorithm for use in radionuclide imaging.
A method is described whereby the edges of computerised radionuclide images can be located by the application of an edge detection algorithm. Results obtained using computer simulated phantoms and radioactive distributions demonstrate the potential accuracy of incorporating such as algorithm into clinical studies.


Determination of Bisphenol A and its chlorinated derivatives in placental tissue samples by liquid chromatography-tandem mass spectrometry.
The group of compounds commonly called endocrine disruptors covers a wide range of synthetic and natural substances able to alter the normal hormone function of wildlife and humans, consequently causing adverse health effects. Bisphenol A (BPA) and its chlorinated derivatives are some of these compounds. In this work, we propose a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine these compounds in human placental tissue samples. The method involves an extraction phase of the extracts from the samples using ethyl acetate, followed by a clean-up phase by centrifugation prior to their quantification by LC-MS/MS using an atmospheric pressure chemical ionization (APCI) interface in the negative mode. Deuterated Bisphenol A (BPA-d(16)) was used as internal standard. Found detection limits (DL) ranged from 0.2 to 0.6 ng g(-1) and quantification limits (QL) from 0.5 to 2.0 ng g(-1) for Bisphenol A and its chlorinated derivatives, while inter- and intra-day variability was under 8.1%. The method was validated using standard addition calibration and a spike recovery assay. Recovery rates for spiked samples ranged from 97% to 105%. This method was satisfactorily applied to the determination of BPA and its chlorinated derivatives in 49 placental tissue samples collected from women who live in the province of Granada (Spain).


Transplantation 1983.
Renal transplantation has entered a new era of optimism characterized by steady increases in our scientific appreciation of the transplant event and improving allograft survival rates. Advances in tissue typing, methods of preventing rejection including an appreciation of the blood transfusion effect and the discovery of new immunosuppressive drugs such as cyclosporin A, and methods of rejection treatment have been responsible for this new era. With renewed impetus, continued advances can only increase an optimistic approach to renal transplantation.


The use of cytotoxic T cells in the regulation of tumour growth in syngeneic mice.
Normal C57BL/6 (B6) spleen cells were cultured with syngeneic EL4 tumour cells, expanded in IL2-containing medium, and tested for anti-tumour activity in vitro and in vivo. The activated cells were highly cytotoxic for EL4 and to a lesser degree killed syngeneic B6 blasts and allogeneic (D2) P815 tumour cells. B6 or BDF1 mice that received these cultured cells by IP injection cleared 125IUdR-labelled EL4 cells faster than untreated mice. However, this enhanced clearance was evident only 7-12 days after injection. Since the injected cells had a short half-life (less than 10% remaining after 48 h) the effect of these cells in vivo was most probably due to the activation of the host's immune system. Mice that received cultured cells survived significantly longer than untreated mice following a lethal dose of EL4 cells. Cultured cells were much more effective in prolonging survival when used in conjunction with cyclophosphamide (CY). In animals receiving either cultured cells with or without CY or CY alone tumour clearance was markedly enhanced 7-12 days after injection. When challenged with a small dose of EL4 tumour cells (1 X 10(4) SC per mouse) three of ten B6 mice treated with B6 anti-EL4 cultured cells were able to survive indefinitely. The frequency of CTL precursors to EL4 from the spleen cells of these surviving animals was about five-fold higher than that of normal spleen cells. Furthermore, CTL derived from primed spleen cells were more specific for EL4 than those derived from normal spleen cells.


Higher risk of stillbirth among lower and middle income women who do not use tobacco, but live with smokers.
To investigate pregnancy outcomes among women living with smokers. Data were from a cohort study of 1,217 women recruited during 3-7th month of pregnancy and 96% followed-up after delivery. The main objective was to investigate effects of smokeless tobacco on pregnancy outcomes. Lower and middle-class neighborhoods in Mumbai, India. Community health volunteers who had good rapport with the local population collaborated with the study personnel to help locate and interact with potential participants. Singleton births from non-tobacco users; n = 924/903/802 for stillbirth/gestational age/birthweight analysis. Non-smoking women who lived with smokers (28%) were categorized as 'exposed' to second hand smoke (SHS). House-to-house surveys with questionnaire administration and medical records abstraction by trained personnel at recruitment and follow-up. Stillbirth (no evidence of life at birth after at least 20 weeks of gestation), low birthweight (<or= 2,499 g) and preterm birth (<or= 258 days of gestation). Rates of low birthweight and preterm birth were not significantly different between exposed and non-exposed. Hazard ratio for stillbirth in SHS exposed women (n = 261) was 2.2 (95% confidence interval 1.1-4.4). Survival times differed significantly between exposed and non-exposed, p = 0.012. Exposed and non-exposed groups differed significantly by education, socioeconomic status, parity and access of antenatal care. After adjustment for these potential confounders in Cox proportional hazards models (gestational age in days as timescale), hazard ratios for stillbirth in the exposed group remained unchanged: 2.1 (1.1-4.3). Pregnant women living with smokers in their household have a significantly higher risk of stillbirth, independent of differences in socio-demographic characteristics and antenatal care.


Vascularisation of pluripotent stem cell-derived myocardium: biomechanical insights for physiological relevance in cardiac tissue engineering.
The myocardium is a diverse environment, requiring coordination between a variety of specialised cell types. Biochemical crosstalk between cardiomyocytes (CM) and microvascular endothelial cells (MVEC) is essential to maintain contractility and healthy tissue homeostasis. Yet, as myocytes beat, heterocellular communication occurs also through constantly fluctuating biomechanical stimuli, namely (1) compressive and tensile forces generated directly by the beating myocardium, and (2) pulsatile shear stress caused by intra-microvascular flow. Despite endothelial cells (EC) being highly mechanosensitive, the role of biomechanical stimuli from beating CM as a regulatory mode of myocardial-microvascular crosstalk is relatively unexplored. Given that cardiac biomechanics are dramatically altered during disease, and disruption of myocardial-microvascular communication is a known driver of pathological remodelling, understanding the biomechanical context necessary for healthy myocardial-microvascular interaction is of high importance. The current gap in understanding can largely be attributed to technical limitations associated with reproducing dynamic physiological biomechanics in multicellular in vitro platforms, coupled with limited in vitro viability of primary cardiac tissue. However, differentiation of CM from human pluripotent stem cells (hPSC) has provided an unlimited source of human myocytes suitable for designing in vitro models. This technology is now converging with the diverse field of tissue engineering, which utilises in vitro techniques designed to enhance physiological relevance, such as biomimetic extracellular matrix (ECM) as 3D scaffolds, microfluidic perfusion of vascularised networks, and complex multicellular architectures generated via 3D bioprinting. These strategies are now allowing researchers to design in vitro platforms which emulate the cell composition, architectures, and biomechanics specific to the myocardial-microvascular microenvironment. Inclusion of physiological multicellularity and biomechanics may also induce a more mature phenotype in stem cell-derived CM, further enhancing their value. This review aims to highlight the importance of biomechanical stimuli as determinants of CM-EC crosstalk in cardiac health and disease, and to explore emerging tissue engineering and hPSC technologies which can recapitulate physiological dynamics to enhance the value of in vitro cardiac experimentation.


Quality of life 1 month after acute pulmonary embolism in emergency department patients.
The Pulmonary Embolism Quality-of-Life (PEmb-QoL) questionnaire assesses quality of life (QoL) after pulmonary embolism (PE). We aimed to determine whether any clinical or pathophysiologic features of PE were associated with worse PEmb-QoL scores 1 month after PE. In this prospective multicenter registry, we conducted PEmb-QoL questionnaires. We determined differences in QoL domain scores for four primary variables: clinical deterioration (death, cardiac arrest, respiratory failure, hypotension requiring fluid bolus, catecholamine support, or new dysrhythmia), right ventricular dysfunction (RVD), PE risk stratification, and subsequent rehospitalization. For overall QoL score, we fit a multivariable regression model that included these four primary variables as independent variables. Of 788 PE patients participating in QoL assessments, 156 (19.8%) had a clinical deterioration event, 236 (30.7%) had RVD of which 38 (16.1%) had escalated interventions. For those without and with clinical deterioration, social limitations had mean (±SD) scores of 2.07 (±1.27) and 2.36 (±1.47), respectively (p = 0.027). For intensity of complaints, mean (±SD) scores for patients without RVD (4.32 ± 2.69) were significantly higher than for those with RVD with or without reperfusion interventions (3.82 ± 1.81 and 3.83 ± 2.11, respectively; p = 0.043). There were no domain score differences between PE risk stratification groups. All domain scores were worse for patients with rehospitalization versus without. By multivariable analysis, worse total PEmb-QoL scores with effect sizes were subsequent rehospitalization 11.29 (6.68-15.89), chronic obstructive pulmonary disease (COPD) 8.17 (3.91-12.43), and longer index hospital length of stay 0.06 (0.03-0.08). Acute clinical deterioration, RVD, and PE severity were not predictors of QoL at 1 month post-PE. Independent predictors of worsened QoL were rehospitalization, COPD, and index hospital length of stay.


Fluoroquinolones as a trigger for rupture of abdominal aortic aneurysm: A case-crossover analysis.
Fluoroquinolones (FQ) are associated with an increased risk of tendinopathy, including rupture. Our study aimed to investigate whether FQ use triggered the rupture of aortic aneurysms using a self-controlled design. We hypothesised that the use of FQ was associated with aortic rupture shortly after redeemed FQ prescriptions. Using nationwide data sources, we performed a case-crossover study of cases with ruptured aortic aneurysms. From 1996 to 2016, 58 persons presented with rupture of an aortic aneurysm and a redeemed prescription for any FQ within 28 days. 67% were men, and the median age was 77 years. Some 82.9% presented with a ruptured abdominal aneurysm. In our conditional regression, the crude OR for having rupture with a recent FQ redemption was 1.36 (CI 1.00-1.86). After adjusting for potential confounders, the OR was 1.35 (CI 0.98-1.85). Changing the hazard period to FQ redemption within 60 and 90 days, the OR was 2.16 (CI 1.70-2.76) and 2.21 (CI 1.78-2.75), respectively. In conclusion, we demonstrated an association between FQ use within 60 and 90 days and a diagnosis of ruptured aortic aneurysm.


A critical analysis of commercially available latex particle reagents for C-reactive protein (CRP) slide agglutination tests.
C-reactive protein (CRP) was assessed in pediatric serum samples using different commercial latex reagents, which were analyzed for species origin of the coating antibodies, homogeneity and density of the latex particles, and prozone agglutinating capacity. All reagents correctly agglutinated the positive and negative control sera. The antibodies coating the particles differed with regard to species origin: one was coated with rabbit, one with horse and goat, one with horse, goat, rabbit and swine, while the reference reagent had horse, goat and rabbit antibodies. Only the monospecies specific antibody-coated latex showed obvious prozoning; this reagent also had the smallest and most homogenous latex particles and showed the most clear-cut reactions. False agglutination was observed at 7-26% according to quantitation with the spot immunoprecipitate assay, which compared favorably with radial immunodiffusion measurements. The lowest percentage of false readings was noted for the rabbit antibody-coated particles; the highest for the reagent with particles coated using antibodies from 4 different species. No reagent had satisfactory precision for the low positive sera between 10 and 40 mg CRP/l.


Genetic variability at the TREX1 locus is not associated with natural resistance to HIV-1 infection.
Three prime repair exonuclease 1 (TREX1) degrades excess HIV-1 DNA, thereby preventing recognition by innate immunity receptors and type I interferon responses. Analyses performed in two HIV-exposed seronegative (HESN) cohorts did not show any differences in TREX1 sequence, single nucleotide polymorphisms frequency, or expression in HESN compared to controls, suggesting that, despite its central role in the HIV-1 infection process, genetic diversity at TREX1 is not a major determinant of susceptibility to infection in humans.


Resistome profiling reveals transmission dynamics of antimicrobial resistance genes from poultry litter to soil and plant.
Poultry farming is a major livelihood in South and Southeast Asian economies where it is undergoing rapid intensification to meet the growing human demand for dietary protein. Intensification of poultry production systems is commonly supported by increased antimicrobial drug use, risking greater selection and dissemination of antimicrobial resistance genes (ARGs). Transmission of ARGs through food chains is an emerging threat. Here, we investigated transmission of ARGs from chicken (broiler and layer) litter to soil and Sorghum bicolor (L.) Moench plants based on field and pot experiments. The results demonstrate ARGs transmission from poultry litter to plant systems under field as well as experimental pot conditions. The most common ARGs could be tracked for transmission from litter to soil to plants were identified as detected were cmx, ErmX, ErmF, lnuB, TEM-98 and TEM-99, while common microorganisms included Escherichia coli, Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, and Vibrio cholerae. Using next generation sequencing and digital PCR assays we detected ARGs transmitted from poultry litter in both the roots and stems of S. bicolor (L.) Moench plants. Poultry litter is frequently used as a fertiliser because of its high nitrogen content; our studies show that ARGs can transmit from litter to plants and illustrates the risks posed to the environment by antimicrobial treatment of poultry. This knowledge is useful for formulating intervention strategies that can reduce or prevent ARGs transmission from one value chain to another, improving understanding of impacts on human and environmental health. The research outcome will help in further understanding the transmission and risks posed by ARGs from poultry to environmental and human/animal health.


[Fluorescent microscopy studies of osteosynthesis and bony defect filling with cyanoacrylate].
Bone defects and osteotomies of the rabbit tibia were stabilized by a mixture of ethyl cyanoacrylate and bone meal. Healing of osteotomy or new bone formations growing through the defect could not be observed.


Smart carnivores think twice: Red fox delays scavenging on conspecific carcasses to reduce parasite risk.
The recent SARS-CoV-2 epidemic has highlighted the need to prevent emerging and re-emerging diseases, which means that we must approach the study of diseases from a One Health perspective. The study of pathogen transmission in wildlife is challenging, but it is unquestionably key to understand how epidemiological interactions occur at the wildlife-domestic-human interface. In this context, studying parasite avoidance behaviours may provide essential insights on parasite transmission, host-parasite coevolution, and energy flow through food-webs. However, the strategies of avoiding trophically transmitted parasites in mammalian carnivores have received little scientific attention. Here, we explore the behaviour of red foxes (Vulpes vulpes) and other mammalian carnivores at conspecific and heterospecific carnivore carcasses using videos recorded by camera traps. We aim to determine 1) the factors influencing the probability of foxes to practice cannibalism, and 2) whether the scavenging behaviour of foxes differ when facing conspecific vs. heterospecific carcasses. We found that red foxes were generally reluctant to consume mesocarnivore carrion, especially of conspecifics. When recorded, consumption by foxes was delayed several days (heterospecific carcasses) or weeks (conspecific carcasses) after carcass detection. Other mammalian scavengers showed a similar pattern. Also, meat-borne parasite transmission from wild carnivore carcasses to domestic dogs and cats was highly unlikely. Our findings challenge the widespread assumption that cannibalistic or intra-specific scavenging is a major transmission route for Trichinella spp. and other meat-borne parasites, especially for the red fox. Overall, our results suggest that the feeding decisions of scavengers are probably shaped by two main contrasting forces, namely the nutritional reward provided by carrion of phylogenetically similar species and the risk of acquiring meat-borne parasites shared with these species. This study illustrates how the detailed monitoring of carnivore behaviour is essential to assess the epidemiological role of these hosts in the maintenance and dispersion of parasites of public and animal health relevance.


Olfactory and chemosomatosensory function in pregnant women assessed with event-related potentials.
The purpose of the study was to better understand past findings of nasal chemosensory hypersensitivity in pregnant women by recording chemosensory event-related potentials (CSERPs) for information about cortical neuronal allocation (amplitudes) and temporal processing (latencies) of three concentrations of pyridine ranging from predominantly olfactory to trigeminal in activation in 15 pregnant and 15 non-pregnant women. CSERP components of primarily sensory (N1 and P2) and cognitive (P3) origin were evaluated. The results displayed no group differences in either N1 or P2 amplitudes or latencies, but tendencies of larger amplitudes and shorter latencies for P3 in pregnant women. This implies that pregnant women's hypersensitivity may more likely be referred to cognitive than sensory processing.


Morin offsets PTZ-induced neuronal degeneration and cognitive decrements in rats: The modulation of TNF-α/TNFR-1/RIPK1,3/MLKL/PGAM5/Drp-1, IL-6/JAK2/STAT3/GFAP and Keap-1/Nrf-2/HO-1 trajectories.
Morin is a bioactive flavonoid with prominent neuroprotective potentials, however, its impact on epilepsy-provoked cognitive dysregulations has not been revealed. Hence, the present investigation aims to divulge the potential anticonvulsant/neuroprotective effects of morin in rats using a pentylenetetrazole (PTZ)-induced kindling model with an emphasis on the possible signaling trajectories involved. Kindling was induced using a sub-convulsive dose of PTZ (35 mg/kg, i.p.), once every other day for 25 days (12 injections). The expression of targeted biomarkers and molecular signals were examined in hippocampal tissues by ELISA, Western blotting, immunohistochemistry, and histopathology. Contrary to PTZ effects, administration of morin (10 mg/kg, i.p., from day 15 of PTZ injection to the end of the experiment) significantly reduced the severity of seizures coupled with a delay in kindling acquisition. It also preserved hippocampal neurons, and diminished astrogliosis to counteract cognitive deficits, exhibited by the enhanced performance in MWM and PA tests. These favorable impacts of morin were mediated via the abrogation of the PTZ-induced necroptotic changes and mitochondrial fragmentation proven by the suppression of p-RIPK-1/p-RIPK-3/p-MLKL and PGAM5/Drp-1 cues alongside the enhancement of caspase-8. Besides, morin inhibited the inflammatory cascade documented by the attenuation of the pro-convulsant receptor/cytokines TNFR-1, TNF-α, I L-1β, and IL-6 and the marked reduction of hippocampal IL-6/p-JAK2/p-STAT3/GFAP cue. In tandem, morin signified its anti-oxidant capacity by lowering the hippocampal contents of MDA, NOX-1, and Keap-1 with the restoration of the impaired Nrf-2/HO-1 pathway. Together, these versatile neuro-modulatory effects highlight the promising role of morin in the management of epilepsy.


Birth distribution in cystic fibrosis and phenylketonuria.
The present study of 977 cystic fibrosis (CF) patients showed a bimodal birth distribution with peaks in April to July and October to January. After adjustment to the monthly variation of the birth rate of all liveborn children there was no significant deviation from the expected distribution. The 387 phenylketonuria (PKU) patients showed no seasonal birth variation.


Evidence for extracellular localization of activator calcium in dog coronary artery smooth muscle as studied by the pyroantimonate method.
Correlated physiological and electron-microscopic studies were made on the source of calcium activating the contractile system (activator calcium) in dog coronary artery smooth muscle fibers. The magnitude of contracture tension induced by 100 mM K+ was dependent on external Ca2+ concentration and reduced or eliminated by factors known to reduce the Ca2+ spike or Ca2+ influx. Little or no mechanical response was elicited by treatments known to cause release of intracellularly stored calcium. These results indicated that the contractile system is mainly activated by the inward movement of extracellular calcium. In accordance with the physiological experiments, electronopaque pyroantimonate precipitate containing calcium was found in the lumina of caveolae, but not in any intracellular structures close to the plasma membrane, when the relaxed fibers were fixed in a 1% osmium tetroxide solution containing 2% potassium pyroantimonate. If the contracted fibers were fixed in the same solution, the pyroantimonate precipitate was diffusely distributed in the myoplasm in the form of numerous particles, while the precipitate in the caveolar lumina was scarcely seen. These findings are discussed in connection with the regulation of intracellular Ca2+ concentration in dog coronary artery smooth muscle.


Increased expression of IL-1 receptors in response to IL-1β may produce more IL-6, IL-8, VEGF, and PGE₂ in senescent synovial cells induced in vitro than in presenescent cells.
Primary synovial cells with high passage number demonstrate increased production of proinflammatory mediators in response to inflammatory stimuli compared with cells with low passage number. This study used synovial cells to learn how different numbers of serial subculture passages affect the production of proinflammatory mediators in response to interleukin (IL)-1β. Synovial cells were serially subcultured in flasks until passage 7. During cell passage, synovial cells were treated with IL-1β for 24 h. Levels of proinflammatory mediators were analyzed by ELISA, real-time PCR, and Western blot. Synovial cells at passage 7 had elongated morphology and higher activity of β-galactosidase, a marker of senescence, than those at passage 3. Production of IL-6, IL-8, vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE(2)) in response to IL-1β was significantly increased in cells at passage 7 compared with passage 3. To evaluate the mechanism of this different response, IL-1 receptor expression was studied in cells stimulated with IL-1β. Compared with cells at passage 3, cells at passage 7 had stronger expression of IL-1 receptors 1 and 2, as well as significantly increased expression of both receptors, in response to IL-1β. This finding suggests that differential production in response to inflammatory stimuli associated with cell passages should be considered when in vitro experiments are used to evaluate the production levels of proinflammatory mediators.


Multi-head deep learning framework for pulmonary disease detection and severity scoring with modified progressive learning.
Chest X-rays (CXR) are the most commonly used imaging methodology in radiology to diagnose pulmonary diseases with close to 2 billion CXRs taken every year. The recent upsurge of COVID-19 and its variants accompanied by pneumonia and tuberculosis can be fatal in some cases and lives could be saved through early detection and appropriate intervention for the advanced cases. Thus CXRs can be used for an automated severity grading of pulmonary diseases that can aid radiologists in making better and informed diagnoses. In this article, we propose a single framework for disease classification and severity scoring produced by segmenting the lungs into six regions. We present a modified progressive learning technique in which the amount of augmentations at each step is capped. Our base network in the framework is first trained using modified progressive learning and can then be tweaked for new data sets. Furthermore, the segmentation task makes use of an attention map generated within and by the network itself. This attention mechanism allows to achieve segmentation results that are on par with networks having an order of magnitude or more parameters. We also propose severity score grading for 4 thoracic diseases that can provide a single-digit score corresponding to the spread of opacity in different lung segments with the help of radiologists. The proposed framework is evaluated using the BRAX data set for segmentation and classification into six classes with severity grading for a subset of the classes. On the BRAX validation data set, we achieve F1 scores of 0.924 and 0.939 without and with fine-tuning, respectively. A mean matching score of 80.8% is obtained for severity score grading while an average area under receiver operating characteristic curve of 0.88 is achieved for classification.


Management of infection during chemotherapy for acute leukemia in Japan: a nationwide questionnaire-based survey by the Japan Adult Leukemia Study Group.
We performed a nationwide questionnaire-based survey to evaluate the current clinical practices of infectious complications during chemotherapy for acute leukemia in Japan. We e-mailed a questionnaire to member institutions of the Japan Adult Leukemia Study Group in September, 2013. The questionnaire consisted of 50 multiple-choice questions covering therapeutic environment, antimicrobial prophylaxis, screening test during neutropenia, empirical therapy for febrile neutropenia, and the use of granulocyte-colony stimulating factor. The results were compared to those of previous surveys conducted in 2001 and 2007, and also to the recommendations described in the guidelines. Usable responses were received from 141 out of 222 (63.5%) institutions. Chemotherapy for acute myeloid leukemia was performed in protective environment in 90% of the institutions, which increased compared to previous survey (76%). Fluoroquinolones and fluconazole were the most commonly used antimicrobial agents for antibacterial and antifungal prophylaxis, followed by sulfamethoxazole-trimethoprim and itraconazole, respectively. In empirical therapy for febrile neutropenia, monotherapy with β-lactum antibiotics was the first-line therapy in most of the institutions. While empirical antifungal therapy was adopted for persistent fever in more than half of the institutions, preemptive/presumptive therapy was also used in approximately 40% of the institutions. Most of the clinicians were reluctant to use granulocyte-colony stimulating factor routinely in chemotherapy for acute myeloid leukemia. This study clarified the current clinical practices of infectious complications during chemotherapy for acute leukemia and would provide important information for the development of a suitable guideline in Japan.


Fluoroscopy-guided vs. navigated iliosacral screw placement with intraoperative 3D scan or postoperative CT control: Impact of the clinical workflow on patients' radiation exposure: Radiation exposure of different workflows for iliosacral screw placement.
To guide iliosacral screws (ISS) and verify safe placement different techniques, e.g. Fluoroscopy-guided (FSG) or 3D navigation are known. However, higher radiation exposure for the conventional technique is a concern. It was the aim of this experimental study to evaluate radiation exposure for three clinical workflows. An anthropomorphic, cross sectional dosimetry phantom was equipped with metal oxide semiconductor field effect transistors to measure organ specific radiation exposure. The effective dose was calculated. Radiation exposure was measured for FSG placement of 2 transverse ISS based on clinical experience regarding fluoroscopy time (240s). Additional measurements were conducted to calculate the effective dose for an intraoperative 3D scan as used for navigated ISS (high-quality 3D), for intraoperative verification of proper guide wire placement (standard-quality 3D) and for postoperative CT, using three different protocols. The following workflows were compared: FSG including postoperative CT (FSG-CT, including 3 different protocols) vs. FSG with intraoperative 3D scan in standard quality (FSG-3D) vs. navigation including two intraoperative 3D scan for navigated ISS (NAV-3D). The effective dose for FSG-CT ranged from 4.41 mSv to 5.27 mSv. FSG-3D resulted in a total of 4.93 mSv. For NAV-3D, the effective dose was the lowest (3.00 mSv). The effective dose of a high-quality 3D scan required for navigation was 1.94 mSv, compared to 1.06 mSv for a standard-quality 3D scan as used for control. Intraoperative 3D scanning may be recommended, either combined with prior FSG ISS placement or following 3D navigation without increasing radiation exposure compared with alternative workflows with postoperative CT control.


Operation overview of a biological waste treatment system during the 4-crew 180-day integrated experiment in the controlled ecological life support system (CELSS).
Waste management and treatment is vital to health care and material circulation, especially in the Controlled Ecological Life Support System (CELSS) with finite resources for long-duration manned space missions. A closed ecological-cycle integrated 4-crew 180-day experiment platform was established to investigate the key technologies such as effective cultivation of higher plant, water treatment and recycling, waste management and treatment. In this study, generated waste during the integrated experiment was classified as renewable and non-renewable waste. The renewable waste including all crew feces and part of inedible plant biomass were treated in a biological system where the aerobic composting technology was utilized. The performance in relation to degradation effect, phytotoxicity and nutrient evaluation was examined during the continuous 180 days. The long-term operation results displayed that 96.26 kg feces and 74.4 kg wheat straw were treated, and 90.6 kg compost product was discharged in nine batches. The microbial community variation was analyzed and Firmicutes, Actinobacteria and Proteobacteria enriched in the compost. The phytotoxicity of compost was examined by seed germination index (GI) and GI of Chinese cabbage ranged from 88% to 132% for all batches. Compared to grown in vermiculite only, the lettuce yield increased 19% when grown in a mixture of vermiculite and processed compost. The summary of this work will be helpful to facilitate future applications of aerobic composting technology as the bio-based waste treatment technology in CELSS.


Transcriptome sequencing and comparative analysis reveal long-term flowing mechanisms in Hevea brasiliensis latex.
The rubber tree, Hevea brasiliensis, is a major commercial source of natural rubber. Increasing the rubber yield of rubber trees is a very serious problem since the demands for high quality rubber materials are great. Establishment of a tapping system is based on an estimate of tapping intensity from the rubber tree. Latex flowing time is one of the most critical factors that determine the rubber yield. Long-term flow is a type of phenomenon of the rubber tree latex with longer flowing time than normal latex flow, and is always caused by intensive tapping. Thus, transcriptome and expression profiling data for long-term flowing latex (LFL) are needed as an important resource to identify genes and to better understand the biological mechanisms of latex flow in rubber trees. The transcripts were sequenced using the Illumina sequencing platform. After cleaning, quality checks and sequencing, 98,697 transcripts and 38,584 unigenes were assembled with the mean size of 1437.31bp and 923.86bp, respectively. In BLAST searches of our database against public databases, 65.17% (25,147) of the unigenes were annotated with gene descriptions, conserved protein domains, or gene ontology terms. Functional categorization further revealed 853 individual unigenes related to long-term flow. According to KEGG classification, the clusters for "cysteine and methionine metabolism", "energy", "oxidative phosphorylation", "terpenoid backbone biosynthesis", "plant hormone signal transduction" and "copper, potassium transporter" were significantly enriched metabolic pathways. We conducted high-resolution transcriptome profiling related to LFL in H. brasiliensis. The research facilitates further studies on gene discovery and on the molecular mechanisms related to the estimation of tapping intensity and prolonging latex flowing time. We concluded that it was necessary to improve energy supplies for intensive tapping and the copper ion content of rubber tree latex could be considered as a standard to estimate tapping intensity.


PET/CT scanning guided intensity-modulated radiotherapy in treatment of recurrent ovarian cancer.
This study was undertaken to evaluate the clinical contribution of positron emission tomography using (18)F-fluorodeoxyglucose and integrated computer tomography (FDG-PET/CT) guided intensity-modulated radiotherapy (IMRT) for treatment of recurrent ovarian cancer. Fifty-eight patients with recurrent ovarian cancer from 2003 to 2008 were retrospectively studied. In these patients, 28 received PET/CT guided IMRT (PET/CT-IMRT group), and 30 received CT guided IMRT (CT-IMRT group). Treatment plans, tumor response, toxicities and survival were evaluated. Changes in GTV delineation were found in 10 (35.7%) patients based on PET-CT information compared with CT data, due to the incorporation of additional lymph node metastases and extension of the metastasis tumor. PET/CT guided IMRT improved tumor response compared to CT-IMRT group (CR: 64.3% vs. 46.7%, P=0.021; PR: 25.0% vs. 13.3%, P=0.036). The 3-year overall survival was significantly higher in the PET-CT/IMRT group than control (34.1% vs. 13.2%, P=0.014). PET/CT guided IMRT in recurrent ovarian cancer patients improved the delineation of GTV and reduce the likelihood of geographic misses and therefore improve the clinical outcome.


Immediate saccade amplitude disconjugacy induced by unequal images.
We tested the ability of normal subjects to make changes in the conjugacy of their saccades. Subjects dichoptically viewed a grid the size of which was 10% larger in one eye. The grids were centred onto a flat screen at 57 cm or 1 m from the subject. Horizontal saccades immediately became larger in the eye viewing the larger grid. For some subjects this disconjugacy persisted even under subsequent monocular viewing. Such persistent changes occurred mainly in the field where the required disconjugacy was divergent for centrifugal saccades, convergent for centripetal saccades. Vertical saccades also developed compensatory disconjugacy; its amplitude was smaller but less variable. To explain these results we propose a fast associative learning mechanism that pairs peripheral disparity with saccades and is capable of producing saccade disconjugacy even in the absence of disparity. For horizontal saccades a secondary conditioning of monocular depth cues by the disparity would also be involved.