The role of efferocytosis-fueled macrophage metabolism in the resolution of inflammation.
The phagocytosis of dying cells by macrophages, termed efferocytosis, is a tightly regulated process that involves the sensing, binding, engulfment, and digestion of apoptotic cells. Efferocytosis not only prevents tissue necrosis and inflammation caused by secondary necrosis of dying cells, but it also promotes pro-resolving signaling in macrophages, which is essential for tissue resolution and repair following injury or inflammation. An important factor that contributes to this pro-resolving reprogramming is the cargo that is released from apoptotic cells after their engulfment and phagolysosomal digestion by macrophages. The apoptotic cell cargo contains amino acids, nucleotides, fatty acids, and cholesterol that function as metabolites and signaling molecules to bring about this re-programming. Here, we review efferocytosis-induced changes in macrophage metabolism that mediate the pro-resolving functions of macrophages. We also discuss various strategies, challenges, and future perspectives related to drugging efferocytosis-fueled macrophage metabolism as strategy to dampen inflammation and promote resolution in chronic inflammatory diseases.


What is remembered about early childhood events?
Almost 100 years ago, Freud identified infantile or childhood amnesia, the difficulty that most adults have remembering events from their first years of life. Recent research in cognitive psychology has in fact demonstrated a paucity of verbal memories of early life experiences. Although Freud believed that childhood memories are repressed, modern explanations for childhood amnesia focus instead on cognitive and social developmental advances of the early preschool years. According to the social interaction hypothesis, a narrative sense of self emerges as a result of parent-child conversations about the past. Implications of autobiographical memory research for models of adult attachment and psychotherapy are discussed.


Management of Aseptic Tibial and Femoral Diaphyseal Nonunions Without Bony Defects.
An evidence-based description of aseptic tibial and femoral diaphyseal nonunions without segmental defects is based on a systematic search of MEDLINE. Aseptic nonunion of the femoral or tibial diaphysis without segmental defects and with an in situ nail, treated with reamed exchange nailing or augmentative plating and bone grafting, has consistently high union rates. Aseptic nonunion without segmental defects and with in situ plate and screw fixation is best managed with revision plate and screw fixation and autogenous bone graft. Various techniques and methods of biological stimulation have relatively high union rates.


Diagnostic Performance of Endoscopic Ultrasound (EUS) for Non-Calcific Chronic Pancreatitis (NCCP) Based on Histopathology.
Studies correlating endoscopic ultrasound (EUS) with histopathology for chronic pancreatitis (CP) are limited by small sample size, and/or inclusion of many patients without CP, limiting applicability to patients with painful CP. The aim of this study was to assess correlation of standard EUS features for CP with surgical histopathology in a large cohort of patients with non-calcific CP (NCCP). Adult patients undergoing total pancreatectomy and islet autotransplantation (TPIAT) for NCCP, between 2008 and 2013, with EUS <1 year before surgery. Histology from resected pancreas at the time of TPIAT (from head, body, and tail) was graded by a GI pathologist blinded to the EUS features. A fibrosis score (FS) ≥2 was abnormal, and FS≥6 was considered severe fibrosis. A multivariate regression analysis for the EUS features predicting fibrosis, after taking age, sex, smoking, and body mass index into consideration, was performed. A quantitative receiver operating characteristic (ROC) curve analysis was performed and Spearman rank correlation co-efficient (r) was calculated. 68 patients (56 females, mean±s.d. age-38.77±10.92) underwent TPIAT for NCCP with pre-operative EUS. ROC curve showed that four or more EUS features provided the best balance of sensitivity (61%), specificity (75%), and accuracy (63%). Although significant, correlation between standard EUS features and degree of fibrosis was poor (r=0.24, P<0.05). Multivariate regression analysis showed that main pancreatic duct irregularity was the only independent EUS feature (P=0.02) which predicted CP. Correlation between standard EUS features and histopathology is poor in NCCP. MPD irregularity is an independent predictor for NCCP.


Equations of state for fluids: empirical temperature dependence of the second virial coefficients.
In this paper, an empirical dependence of the second virial coefficients is derived from equations of state. The second virial coefficient B2 is found to be a linear function of 1/T1+beta, where T is the temperature and beta is a constant and has different value for different substances. Excellent experimental supports to this relationship are reported for nonpolar fluids, polar fluids, heavy globular molecule fluids, and quantum fluid He-4.


UV inactivation of adenovirus type 41 measured by cell culture mRNA RT-PCR.
Adenoviruses are among the most resistant waterborne pathogens to UV disinfection, yet of the 51 serologically distinct human adenoviruses, only a few have been evaluated for their sensitivities to UV irradiation. Human enteric adenoviruses (Ad40 and Ad41) are difficult to cultivate and reliably assay for infectivity, requiring weeks to obtain cytopathogenic effects (CPE). Inoculated cell cultures often deteriorate before the appearance of distinctive CPE making it difficult to obtain reliable and reproducible data regarding UV inactivation. Adenovirus is a double-stranded DNA virus and produces messenger RNA (mRNA) during replication in host cells. The presence of viral mRNA in host cells is definitive evidence of infection. We recently developed a rapid and reliable cell culture-mRNA RT-PCR assay to detect and quantify adenovirus infectivity. Viral mRNA recovered from cell cultures 5-7 days after infection was purified on oligo-dT latex, treated with DNase, and amplified by RT-PCR using the primers specific for a conserved region of the hexon late mRNA transcript. Treatment of approximately 10(4) Ad41 with different doses of 254 nm germicidal UV radiation resulted in a dose-dependent loss of infectivity. As UV doses were increased from 75 to 200 mJ/cm2, virus survival decreased and no virus infectivity (measured by detectable mRNA) was found at a dose of 225 mJ/cm2 or higher. Our results using the cell culture mRNA RT-PCR assay indicate that Ad41 is more resistant to UV radiation than in a previous study using a conventional cell culture infectivity assay. Results were more similar to those found for Ad 40 using CPE as a measure of infectivity in another previous study.


Cerebral revascularization model in a swine.
The purpose of this study was to analyze the suitability of the cerebral vasculature of the pig regarding a revascularization procedure. In two 60 kg pigs the femoral artery was exposed and canulated for selective angiography and interventional procedures. After the angiography, the pigs were brought to the animal OR for craniotomy and analysis of the intracranial cerebral arteries and the surgical exposure of the carotid arteries under the microscope. Angiography demonstrated the presence of a true internal-, external carotid artery and vertebral arteries. Both the vertebral and internal carotid arteries are feeding a rete mirabilis both at the cranial base and the cranio-cervical junction. At these sites further advancement of the angiography catheter was not possible. Out of these rete mirabilis, an intracranial carotid artery and an intracranial vertebral artery were formed, respectively. The intracranial cerebral vessels were of the dimension of 1 mm and less. The extracranial portion of the internal carotid artery was 2.5 mm of diameter. From these findings, we conclude that a direct cerebral revascularization procedure of the intracranial vessels is not possible in the swine. However, a global revascularization procedure on the extracranial portion of the internal carotid artery is thus feasible, both using a low- and high-flow anastamosis technique.


Impact of Thiotepa-Based Autologous Hematopoietic Cell Transplantation in Primary Central Nervous System Lymphoma in First Complete Remission: A University of California Hematologic Malignancies Consortium Retrospective Analysis.
The choice between nonmyeloablative chemotherapy (NMA-C) or autologous hematopoietic cell transplantation (autoHCT) as consolidation in primary central nervous system lymphoma (PCNSL), and timing of autoHCT differs among centers. We aimed to clarify these points. We retrospectively analyzed PCNSL adult patients who received consolidation in CR1 or underwent autoHCT during their treatment course. Cohort A included those who underwent autoHCT in CR1, cohort B included those who underwent NMA-C in CR1, and cohort C included patients who underwent autoHCT in CR2+. We compared cohorts A and B, and cohorts A and C. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS), treatment-related mortality (TRM) and cumulative incidence of relapse (CIR). 36 patients were included in cohort A, 30 in cohort B, and 14 in cohort C. The 5-year OS for cohorts A vs B and vs C were 90.7% vs 62.8% (P = .045) and vs 77.9% (P = .32), respectively. The 5-year PFS from diagnosis for cohorts A vs B was 87.8% vs 37.3% (P < .001). The 5-year PFS from autoHCT for cohorts A vs C was 87.6% vs 58.4% (P = .023). The 5-year TRM and CIR in cohorts A vs B was 9.4% vs 9.5% (P = .674), and 2.9% vs 53.2% (P < .001), respectively. The 5-year TRM and CIR in cohorts A vs C from the time of autoHCT was 9.5% vs 22.1% (P = .188), and 2.9% vs 19.5% (P = .104), respectively. Despite the limitations, thiotepa-based autoHCT in CR1 appears to improve outcomes in eligible patients with PCNSL.


Major Surgery and Long Term Cognitive Outcomes: The Effect of Postoperative Delirium on Dementia in the Year Following Discharge.
Delirium is among the most common complications following major surgery. Delirium following medical illness is associated with the development of chronic cognitive decline. The objective of this study was to determine the association of postoperative delirium with dementia in the year following surgery. This was a retrospective cohort study in a large health network (January 2013 to December 2019). All patients over age 50 undergoing surgery requiring an inpatient stay were included. Our main exposure was an episode of delirium. The primary outcome was a new dementia diagnosis in the 1 y following discharge. Secondary outcomes included hospital length of stay, non-home discharge destination, mortality and rehospitalizations in 1 y. There were 39,665 patients included, with a median age of 66. There were 4156 of 39,665 emergencies (10.5%). Specialties were general surgery (12,285/39,665, 31%) and orthopedics (11,503/39,665, 29%). There were 3327 (8.4%) patients with delirium. Delirious patients were older and were more likely to have comorbid conditions and undergone complex procedures. There were 1353 of 39,665 (3.5%) patients who developed dementia in the year following their surgery; 4930 of 39,665 (12.4%) who died; and 8200 of 39,665 (20.7%) who were readmitted. Delirium was associated with a new dementia diagnosis after adjusting for baseline characteristics (Odds ratio [OR] 13.9; 95% CI, 12.2-15.7). Similarly, delirium was also associated with 1 y mortality (OR 3.1; 95% CI 2.9-3.4) and readmission (OR 1.9, 95% CI 1.7-2.0). Postoperative delirium is the strongest factor associated with development of dementia in the year following a major operation. Strategies to prevent, identify, and treat delirium in the postoperative setting may improve long-term cognitive recovery.


Relationship between soil and groundwater salinity in the Western Canada Sedimentary Basin.
Saturated soil paste extracts indicate soluble ions in soil pore water that are available to vegetation. As such, they are thought to accurately describe the relationship between soil and groundwater salinity. To test this assumption, soil and groundwater samples were collected from 575 monitoring wells in saline regions of the Western Canadian Sedimentary Basin (WCSB). Samples were analyzed for electrical conductivity (EC) and Cl-, Na+, Ca2+, Mg2+, K+, SO42-, and HCO- 3 content. We compared groundwater ionic concentrations to paste extracts derived from matching soils, finding that differences from in situ soil porosity cause saturated pastes to underestimate groundwater salinity. Therefore, we provide pedotransfer functions for accurately calculating groundwater quality from soil data. In addition, we discuss the effects of porosity and soil composition on the saturated paste method, as measured through hydraulic conductivity, saturation percent, and sample lithology. Groundwater salinity may also influence further leaching of salts from soil. As produced water (NaCl brine) spills are common across the sulfate-rich soils of the WCSB, we considered the effects of NaCl on leaching of other ions, finding that influx of Na+ into groundwater is associated with increased sulfate leaching from soil. Therefore, considering the secondary effects of produced water on groundwater quality is essential to spill management.


Effect of neuromuscular electrical stimulation on functional exercise capacity in patients undergoing cardiac surgery: A randomized clinical trial.
To evaluate the effects of neuromuscular electrical stimulation on functional capacity of patients in the immediate postoperative period of cardiac surgery. A prospective, randomized controlled trial. A cardiac surgery specialist hospital in Aracaju, Sergipe, Brazil. Subjects: Patients in the postoperative period of cardiac surgery. The control group received the conventional physiotherapy and the intervention group received neuromuscular electrical stimulation of the rectus femoris and gastrocnemius muscles bilaterally, applied for 60 min, twice a day for up to 10 sessions per patient, in the immediate postoperative period until postoperative day 5. The primary outcome was the distance walked, which was evaluated using the 6-min walk test on postoperative day 5. Secondary outcomes were gait speed, lactate levels, muscle strength, electromyographic activity of the rectus femoris and Functional Independence Measure, some of them evaluated on preoperative and postoperative period. Of 132 eligible patients, 88 patients were included and randomly allocated in two groups, and 45 patients were included in the analysis. No significant difference was found on the distance walked (p = 0.650) between patients allocated in intervention group (239.06 ± 88.55) and control group (254.43 ± 116.67) as well as gait speed (p = 0.363), lactate levels (p = 0.302), knee extensor strength (p = 0.117), handgrip strength (p = 0.882), global muscle strength (p = 0.104), electromyographic activity (p = 0.179) and Functional Independence Measure (p = 0.059). Although the effects are still uncertain, the use of neuromuscular electrical stimulation carried out in five days didn't present any benefit on functional capacity of patients in the immediate postoperative period of cardiac surgery.


[The clinical assessment of zygomatic complex fracture treated via infraorbital incision and rigid fixation].
To investigate the clinical effect of zygomatic complex (ZC) fracture via infraorbital incision and rigid fixation. To clinically classify 65 cases with ZC fractures,which treated with open reduction and minor titanium-plate internal fixation. (1) The operated area can be widely exposed via infraorbital incision. (2) ZC fractures can be reducted timely and correctly. (3) The fragments can be fixed rigidly with minor Ti-plaets. No injury to the facial nerve.The satisfactory rate of recovery was 95.4% (63/65). Operation through infraorbital incision is suitable to ZC fractures.


An automated snoring sound classification method based on local dual octal pattern and iterative hybrid feature selector.
In this research, a novel snoring sound classification (SSC) method is presented by proposing a new feature generation function to yield a high classification rate. The proposed feature extractor is named as Local Dual Octal Pattern (LDOP). A novel LDOP based SSC method is presented to solve the low success rate problems for Munich-Passau Snore Sound Corpus (MPSSC) dataset. Multilevel discrete wavelet transform (DWT) decomposition and the LDOP based feature generation, informative features selection with ReliefF and iterative neighborhood component analysis (RFINCA), and classification using k nearest neighbors (kNN) are fundamental phases of the proposed SSC method. Seven leveled DWT transform, and LDOP are used together to generate low, medium, and high levels features. This feature generation network extracts 4096 features in total. RFINCA selects 95 the most discriminative and informative ones of these 4096 features. In the classification phase, kNN with leave one out cross-validation (LOOCV) is used. 95.53% classification accuracy and 94.65% unweighted average recall (UAR) have been achieved using this method. The proposed LDOP based SSC method reaches 22% better result than the best of the other state-of-the-art machine learning and deep learning-based methods. These results clearly denote the success of the proposed SSC method.


Kinetics of histone gene expression during early development of Xenopus laevis.
Using literature data for transcriptional and translational rate constants, gene copy numbers, DNA concentrations, and stability constants, we have calculated the expected concentrations of histones and histone mRNA during embryogenesis of Xenopus laevis. The results led us to conclude that: (i) for X. laevis the gene copy number of the histone genes is too low to ensure the synthesis of sufficient histones during very early development, inheritance from the oocyte of either histone protein or histone mRNA (but not necessarily both) is necessary; (ii) from the known storage of histones in the oocyte and the rates of histone synthesis determined by Adamson & Woodland (1977), there would be sufficient histones to structure the newly synthesized DNA up to gastrulation but not thereafter (these empirical rates of histone synthesis may be underestimates); (iii) on the other hand, the amount of H3 mRNA recently observed during early embryogenesis (Koster, 1987, Koster et al., 1988) could direct a higher and sufficient synthesis of H3 protein, also after gastrulation. We present a quantitative model that accounts both for the observed H3 mRNA concentration as a function of time during embryogenesis and for the synthesis of sufficient histones to structure the DNA throughout early embryogenesis. The model suggests that X. laevis exhibits a major (i.e. some 14-fold) reduction in transcription of histone genes approximately 11 hours after fertilization. This reduction could be due to a decrease in the number of transcribed histone genes, a decreased rate constant of transcription with continued transcription of all the histone genes, and/or a reduction in the time during the cell cycle in which histone mRNA synthesis takes place. Alternatively, the histone mRNA stability might decrease approximately 16-fold 11 hours after fertilization.


Schistosomiasis of the spinal cord.
Involvement of the central nervous system is a rare complication of schistosomiasis. A case is reported which manifested as a granulomatous, transverse myelitis in a 13-month-old child. Removal of the granuloma resulted in return of motor function.


Ultra-weak photon emission from biological samples: definition, mechanisms, properties, detection and applications.
This review attempts to summarize molecular mechanisms, spectral and intensity properties, detection techniques and applications of ultra-weak photon emission. Ultra-weak photon emission is the chemiluminescence from biological systems where electronically excited species are formed during oxidative metabolic or oxidative stress processes. It is generally accepted that photons are emitted (1) at near UVA, visible, and near IR spectral ranges from 350 to 1300nm and (2) at the intensity of photon emission in the range of several units to several hundreds (oxidative metabolic process) and several hundreds to several thousands (oxidative stress process) photons s(-1)cm(-2). Current development in detection using low-noise photomultiplier tubes and imaging using highly sensitive charge coupled device cameras allows temporal and spatial visualization of oxidative metabolic or oxidative stress processes, respectively. As the phenomenon of ultra-weak photon emission reflects oxidative metabolic or oxidative stress processes, it can be widely used as a non-invasive tool for monitoring of the physiological state of biological systems.


Modification of haemophiliac haemorrhage pain by transcutaneous electrical nerve stimulation.
Haemophiliacs suffer considerable pain when they bleed into their joints. This study investigated the use of transcutaneous electrical nerve stimulation (TENS) for relief of such pain. Thirty-six haemophiliac patients received either active or placebo TENS treatment. The intensity of pain was assessed before and after treatment using the McGill Pain Questionnaire. After 25 min of active treatment, 71% of the subjects reported at least 50% pain relief as measured by the McGill Pain Questionnaire. This compares with only 25% pain relief experienced by the placebo group.


Translocations in normal B cells and cancers: insights from new technical approaches.
Chromosomal translocations are recurrent genetic events that define many types of cancers. Since their first description several decades ago as defining elements in cancer cells, our understanding of the mechanisms that determine their formation as well as their implications for cancer progression and therapy has remarkably progressed. Chromosomal translocations originate from double-strand breaks (DSBs) that are brought into proximity in the nuclear space and joined inappropriately by DNA-repair pathways. The frequency and pattern of translocations are influenced by perturbations of any of these events. DSB formation is heavily determined by physiologic processes, such as the activity of RAG1/2 and AID enzymes during B-cell development or maturation, or by pathologic factors, such as ionizing radiations, ROS, or fragile sites. Cellular processes of mRNA transcription, DNA replication, and repair can influence the chromosomal territories and modify the relative position and proximity of genes inside the nucleus. DNA-repair factors contribute not only to the maintenance of genome integrity but also to translocations in normal and cancer cells. Next-generation sequencing techniques provide an unprecedented and powerful tool to approach the field of chromosomal translocations. Using specific examples, we will explain how genome-wide translocation mapping methods, such as high-throughput genomic translocation sequencing (HTGTS) and translocation-capture sequencing, combined with large-scale methods to determine nuclear proximity of genes or chromosome domains, such as 4C and Hi-C, have changed our view of the factors and the rules governing translocation formation in noncancer cells. Finally, we will review chromosomal rearrangements and newly described findings, such as chromothripsis, in cancer cells based on these novel rules on translocation formation.


Human hepatoma cell lines on gas foaming templated alginate scaffolds for in vitro drug-drug interaction and metabolism studies.
Liver in vitro systems that allow reliable prediction of major human in vivo metabolic pathways have a significant impact in drug screening and drug metabolism research. In the present study, a novel porous scaffold composed of alginate was prepared by employing a gas-in-liquid foaming approach. Galactose residues were introduced on scaffold surfaces to promote cell adhesion and to enhance liver specific functions of the entrapped HepG2/C3A cells. Hepatoma cells in the gal-alginate scaffold showed higher levels of liver specific products (albumin and urea) and were more responsive to specific inducers (e.g. dexamethasone) and inhibitors (e.g. ketoconazole) of the CYP3A4 system than in conventional monolayer culture. HepG2/C3A cells were also more efficient in terms of rapid elimination of testosterone, used as a model substance, at rates comparable to those of in vivo excretion. In addition, an improvement in metabolism of testosterone, in terms of phase II metabolite formation, was also observed when the more differentiated HepaRG cells were used. Together the data suggest that hepatocyte/gas templated alginate-systems provide an innovative high throughput platform for in vitro drug metabolism and drug-drug interaction studies, with broad fields of application, and might provide a valid tool for minimizing animal use in preclinical testing of human relevance.


Small-angle scattering for beginners.
Many experimental methods are available for the characterization of nanostructures, but most of them are limited by stringent experimental conditions. When it comes to analysing nanostructures in the bulk or in their natural environment - even as ordinary as water at room temperature - small-angle scattering (SAS) of X-rays or neutrons is often the only option. The rapid worldwide development of synchrotron and neutron facilities over recent decades has opened unprecedented possibilities for using SAS in situ and in a time-resolved way. But, in spite of its huge potential in the field of nanomaterials in general, SAS is covered far less than other characterization methods in non-specialized curricula. Presented here is a rigorous discussion of small-angle scattering, at a technical level comparable to the classical undergraduate coverage of X-ray diffraction by crystals and which contains diffraction as a particular case.


Metabolic fate and effect on cholesterol removal of liposomes prepared from 1,3-di-O-octadecenylglycero-2-phosphocholine studied in vivo and in vitro.
Available methodology was adapted to synthesize a labeled diether analog of 2-phosphatidylcholine (1,3-di-O-9'-cis-[9',10' (n)-3H]octadecenylglycero-2-phosphocholine [( 3H]DOE-2-PC). Unilamellar liposomes prepared by sonication from this phospholipid were injected into rats and, 4 h later, 65-78% of injected label was recovered in the liver. Thereafter, liver radioactivity disappeared with a half-life of 2-3 days. The radioactivity lost from the liver was recovered in the feces and in bile. Analysis of liver radioactivity showed that at all time intervals examined (4 h to 3 days after injection), 90% of the label remained as phospholipid. These findings provide evidence that this structural isomer is not readily metabolized, but is fairly rapidly eliminated from the liver. Of the 10% recovered as neutral lipid, 70% comigrated with diacylglycerol and 30% with triacylglycerol. Similar results were obtained when human hepatoma G2 cells in culture were incubated with [3H]DOE-2-PC liposomes. Following incubation of liposomes with liver homogenates, up to 10% conversion of [3H]DOE-2PC to neutral lipid occurred at pH 4.6, but not at pH 7.4. These data show that conversion of [3H]DOE-2-PC to dialkenylglycerol is catalyzed by a lysosomal enzyme. In separate experiments with cultured cells, sonicated dispersions of DOE-2-PC were mixed with high-density apolipoprotein and were shown to enhance markedly cellular cholesterol efflux. This novel diether phospholipid fulfills some of the criteria required of liposomes for their ability to remove cholesterol from the periphery as well as for drug delivery to the liver, i.e., stability in the circulation, marked hepatic uptake, slow metabolism, and elimination from the body.


[Competing endogenous RNA regulation mechanism and its role in the development and progression of colorectal cancer].
MicroRNAs are negative regulators of mRNA, and latest studies show that "mRNAs can also inhibit microRNAs". With these reciprocal interactions, different mRNAs with identical "microRNA binding site" cim regulate each other by competitively binding to the same microRNA pool. This is the novel competing endogenous RNA (ceRN A)regulating mechanism. The ceRN A mechanism, which is a totally new regulating mechanism , greatly expands the regulatory network across genes. It has been proved by experimental evidence that, in HCT116 colon cancer cells,KRAS and PTEN , ZEB2 and PTEN can regulate each other by ceRNA mechanism.


DHEA-induced modulation of renal gluconeogenesis, insulin sensitivity and plasma lipid profile in the control- and dexamethasone-treated rabbits. Metabolic studies.
In view of antidiabetic and antiglucocorticoid effects of dehydroepiandrosterone (DHEA) both in vitro and in vivo studies were undertaken: (i) to elucidate the mechanism of action of both dexamethasone phosphate (dexP) and DHEA on glucose synthesis in primary cultured rabbit kidney-cortex tubules and (ii) to investigate the influence of DHEA on glucose synthesis, insulin sensitivity and plasma lipid profile in the control- and dexP-treated rabbits. Data show, that in cultured kidney-cortex tubules dexP significantly stimulated gluconeogenesis by increasing flux through fructose-1,6-bisphosphatase (FBPase). DexP-induced effects were dependent only upon glucocorticoid receptor. DHEA decreased glucose synthesis via inhibition of glucose-6-phosphatase (G6Pase) and suppressed the dexP-induced stimulation of renal gluconeogenesis. Studies with the use of inhibitors of DHEA metabolism in cultured renal tubules showed for the first time that DHEA directly affects renal gluconeogenesis. However, in view of analysis of glucocorticoids and DHEA metabolites levels in urine, it seems likely, that testosterone may also contribute to DHEA-evoked effects. In dexP-treated rabbits, plasma glucose level was not altered despite increased renal and hepatic FBPase and G6Pase activities, while a significant elevation of both plasma insulin and HOMA-IR was accompanied by a decline of ISI index. It thus appears that increased insulin levels were required to maintain normoglycaemia and to compensate the insulin resistance. DHEA alone affected neither plasma glucose nor lipid levels, while it increased insulin sensitivity and diminished both renal and hepatic G6Pase activities. Surprisingly, DHEA co-administrated with dexP did not alter insulin sensitivity, while it partially suppressed the dexP-induced elevation of renal G6Pase activity and plasma cholesterol and triglyceride contents. As (i) gluconeogenic pathway in rabbit is similar to that in human, and (ii) DHEA counteracts several dexP-evoked effects, it seems likely, that its supplementation might be beneficial to patients treated with glucocorticoids.


Anomalous left circumflex coronary artery: "normal" variant of uncertain clinical and pathologic significance.
Anomalous origin of the left circumflex artery from the aorta is generally viewed as a benign coronary arterial anomaly. Three such cases are reported in which the anomalous artery was totally occluded. Although coronary atherosclerosis was present in all three cases, the proximal segment of the anomalous circumflex vessel was particularly severely affected in each patient. Two patients had a myocardial infarct in the distribution of the aberrant vessel. Accurate angiographic diagnosis is needed before cardiac surgery is performed, whether for valve replacement or myocardial revascularization, because this variant may be less benign than one believed.


Morphological characterisation and phylogenetic relationships of Zschokkella candia n. sp. from the gall-bladder of Sparisoma cretense (L.) (Perciformes: Scaridae) in the Sea of Crete off Greece.
A new myxosporean parasite, Zschokkella candia n. sp., from the gall-bladder of the wild parrotfish Sparisoma cretense (L.) (Perciformes: Scaridae) is described based on light and scanning electron microscopy. Mature spores are elliptical, with mean dimensions 11.2 ± 0.5 × 7.8 ± 0.1 μm and possess spherical polar capsules with mean diameter of 2.3 ± 0.3 μm. The new species is differentiated from other similar species of the genus based on spore morphology, its coelozoic life-style and molecular data. The phylogenetic tree constructed using maximum likelihood analysis of small subunit (SSU) rDNA sequence data complements the characterisation of Zschokkella candia n. sp. by defining its phylogenetic position among the species of Zschokkella Auerbach, 1909 sequenced to date. The phylogenetic analysis supports the existing knowledge on the complicated polyphyletic relationships among the members of the genus Zschokkella.


Correction of hemophilia B in canine and murine models using recombinant adeno-associated viral vectors.
Hemophilia B, or factor IX deficiency, is an X-linked recessive disorder occurring in about 1 in 25,000 males. Affected individuals are at risk for spontaneous bleeding into many organs; treatment mainly consists of the transfusion of clotting factor concentrates prepared from human blood or recombinant sources after bleeding has started. Small- and large-animal models have been developed and/or characterized that closely mimic the human disease state. As a preclinical model for gene therapy, recombinant adeno-associated viral vectors containing the human or canine factor IX cDNAs were infused into the livers of murine and canine models of hemophilia B, respectively. There was no associated toxicity with infusion in either animal model. Constitutive expression of factor IX was observed, which resulted in the correction of the bleeding disorder over a period of over 17 months in mice. Mice with a steady-state concentration of 25% of the normal human level of factor IX had normal coagulation. In hemophilic dogs, a dose of rAAV that was approximately 1/10 per body weight that given to mice resulted in 1% of normal canine factor IX levels, the absence of inhibitors, and a sustained partial correction of the coagulation defect for at least 8 months.


Limber neurons for a nimble mind.
In this issue of Neuron, Stokes et al. (2013) demonstrate that cortical neurons that adapt their properties with task demands form patterns reflecting the shifting mental states needed to solve the task. Adaptive neurons may be critical to hallmarks of cognition: behavioral complexity and flexibility.


Plastid trnF pseudogenes are present in Jaltomata, the sister genus of Solanum (Solanaceae): molecular evolution of tandemly repeated structural mutations.
Extensive gene duplication arranged in a tandem array is rare in the plastome of embryophytes. Interestingly, we found pseudogene copies of the trnF gene in the genus Jaltomata, the sister genus of Solanum where such gene duplication has been previously reported. In each Jaltomata sequence available we found two pseudogene copies in close 5'-proximity to the original functional gene. The size of each pseudogene copy ranged between 17 and 48 bp and the anticodon domain was identified as the most conserved element. A common ATT(G)n motif is particularly interesting and its modifications were found to border the 3' of the duplicated regions. Other motifs were partial residues, or entire parts of the T- and D-domains, and both domains proved to be variable in length among the pseudogenes identified. The residues of the 3' and 5' acceptor stem were not found among the copies. We further compared the newly discovered copies of Jaltomata with those ones previously described from Solanum and inferred phylogenetic relationships of the copies aligned. The evolution of Solanum copies, in contrast to Jaltomata, is hard to explain as resulting only in parsimonious changes since reticulate evolutionary patterns were detected among the copies. The dynamic evolutionary patterns of Solanum might be explained by possible inter- or intrachromosomal recombination.


Acetamide hydrolyzing activity of Bacillus megaterium F-8 with bioremediation potential: optimization of production and reaction conditions.
Bacillus megaterium F-8 exhibited an intracellular acetamide hydrolyzing activity (AHA) when cultivated in modified nutrient broth with 3% tryptone, 1.5% yeast extract, and 0.5% sodium chloride, at pH 7.2, 45 °C for 24 h. Maximum AHA was recorded in the culture containing 0.1 M of sodium phosphate buffer, (pH 7.5) at 45 °C for 20 min with 0.2 % of acetonitrile and resting cells of B. megaterium F-8 equivalent to 0.2 ml culture broth. This activity was stable up to 55 °C and was completely inactivated at or above 60 °C. Maximum acyl transferase activity (ATA) was recorded in the reaction medium containing 0.1 M of potassium phosphate buffer, (pH 8.0) at 55 °C for 5 min with 0.85 mM of acetamide as acyl donor and hydroxylamine hydrochloride as acyl acceptor and resting cells of B. megaterium F-8 equivalent to 0.94 mg cells (dry weight basis). This activity was stable up to 60 °C and a rapid decline in enzyme activity was recorded above it. Under the optimized conditions, this organism hydrolyzed various nitriles and amides such as propionitrile, propionamide, caprolactam, acetamide, and acrylamide to corresponding acids. Acyl group transfer capability of this organism was used for the production of acetohydroxamic acid. ATA of B. megaterium F-8 showed broad substrate specificity such as for acetamide followed by propionamide, acrylamide, and lactamide. This amide hydrolyzing and amidotransferase activity of B. megaterium F-8 has potential applications in enzymatic synthesis of hydroxamic acids and bioremediation of nitriles and amides contaminated soil and water system.


Effects of a transitional care program for individuals with limbs disabilities living in a rural community: A randomized controlled trial.
Transitional care (TC) has been proven to be effective in addressing fragmented care and preventing adverse outcomes for chronically ill patients transitioning from hospital to home, but the definitive description of TC that was used successfully for individuals with limbs disability has not been formed in the context of health care reform in China. The aim of this study was to evaluate the effect of a TC program on health outcomes in individuals with limbs disability based on an original community for healthcare. It was a randomized controlled trial. Individuals in the intervention group received ongoing rehabilitation both at the specialized care center and at home through multidisciplinary team, while individuals in the control group received routine follow-up visits by primary healthcare physicians. Outcomes were measured by Short-Form Health Survey-36 (SF-36), Modified Barthel Index (MBI) and Caregiver Strain Index (CSI) at 3 and 6 months respectively. A total of 84 participants were randomly assigned (intervention n = 42, control n = 42). Mean values of Physical Components Summary, an integral component of SF-36, was significantly better in the intervention group at 3 and 6 months (42.0 ± 2.3 and 44.3 ± 1.5 respectively). The same trend was observed in MBI (72.2 ± 6.8 and 78.6 ± 9.3 at 3 and 6 months respectively). But the significant improvement in CSI was only observed at 6 months. There were significant differences between groups in these scores except Mental Components Summary. The TC program has been proven to be feasible and improve health-related outcomes.


Whole-Brain Radiation Therapy Versus Stereotactic Radiosurgery for Cerebral Metastases.
Whole-brain radiation therapy (WBRT) was frequently used to treat brain metastases in the past. Stereotactic radiosurgery (SRS) is now generally preferred to WBRT for patients with limited brain metastases. SRS can also be used to treat extensive brain metastases (>10-15 metastases), and clinical trials are currently comparing WBRT with SRS for extensive disease. SRS may allow for an increased risk of radiation necrosis or leptomeningeal disease dissemination after treatment. Preoperative SRS and multifraction radiotherapy decrease the risk of these side effects and may soon become standard of care. Combining SRS with immune checkpoint inhibitors may improve patient outcomes.


Structural basis for the inhibition of porcine pepsin by Ascaris pepsin inhibitor-3.
The three-dimensional structures of pepsin inhibitor-3 (PI-3) from Ascaris suum and of the complex between PI-3 and porcine pepsin at 1. 75 A and 2.45 A resolution, respectively, have revealed the mechanism of aspartic protease inhibition by this unique inhibitor. PI-3 has a new fold consisting of two domains, each comprising an antiparallel beta-sheet flanked by an alpha-helix. In the enzyme-inhibitor complex, the N-terminal beta-strand of PI-3 pairs with one strand of the 'active site flap' (residues 70-82) of pepsin, thus forming an eight-stranded beta-sheet that spans the two proteins. PI-3 has a novel mode of inhibition, using its N-terminal residues to occupy and therefore block the first three binding pockets in pepsin for substrate residues C-terminal to the scissile bond (S1'-S3'). The molecular structure of the pepsin-PI-3 complex suggests new avenues for the rational design of proteinaceous aspartic proteinase inhibitors.


Corrigendum: Habitual Behavior and Dopamine Cell Vulnerability in Parkinson Disease.
[This corrects the article on p. 99 in vol. 9, PMID: 26300740.].


An investigation of complete denture teaching in the UK: part 1. A survey of undergraduate teaching.
This paper is the first in a series of two that investigate the undergraduate teaching of complete dentures in the UK. A questionnaire was sent by email to 13 UK dental schools enquiring about the number of hours spent in the lecture theatre, laboratory and clinic. The schools were also asked to give their views about the preparedness of the new graduates for dealing with complete dentures in general practice. There was great disparity between schools in the overall number of lectures delivered. Two schools claimed 28 hours and the remainder varied between 6-15 hours. Four schools devoted more time to laboratory work whereas three schools spent more time in the clinic. One school reported no dedicated clinical time for complete dentures. There appears to be a regional variation with northern UK dental schools spending more time on the teaching of complete dentures. The quota for complete dentures varied from three in most schools to eight in one school and none in another. Comments from the dental schools varied from a reported lack of suitable complete denture cases, to concerns with insufficient curricular time devoted to the subject and a subsequent lack of clinical competence on graduation. Some schools have integrated complete denture teaching into the general prosthodontic course as it is considered inappropriate to teach different aspects of prosthetics in isolation. Competence in complete dentures falls short of what is expected. With a single exception all the schools seem to have low expectations for their undergraduate students to be practically trained and experienced in the production of complete dentures. Despite the advent of implants and the introduction of clinical dental technicians, there is and will continue to be a need for the competent treatment of the edentulous population by general practitioners.


A comparison of wheat germ agglutinin binding between normal and sickle red blood cells.
Using the label-fracture technique, an ultrastructural comparison was made of the number and distribution of wheat germ agglutinin (WGA)-binding sites between human normal and sickle red blood cells. The WGA was adsorbed to colloidal gold, and quantitative analysis of the electron micrographs revealed that more binding sites were present on the sickle erythrocytes than on the normal erythrocytes. Moreover, the sites were more clustered on the sickle red cells than on the normal red cells. Use of another lectin, Bandieraea simplicifolia-II, revealed that it did not bind to normal or sickle red cells. Because of the affinity of the WGA for sialic acid residues, it is probable that the WGA is binding to a transmembrane sialoglycoprotein, glycophorin A. The conformation and/or distribution of the glycophorin A molecules may be altered by the sickle hemoglobin that binds to the red cell membrane. Hence, as detected by WGA, new surface receptors, which could play a role in the adhesion of sickle cells to endothelium may be exposed.


Effects of pimozide on the ultrastructure of the pars distalis in the rat.
The effects of pimozide, a dopamine receptor-blocking agent, were studied in the pars distalis of the rat. The animals received 100 micrograms/100 g pimozide daily for 5, 10, 15, and 20 days. Pimozide induces striking ultrastructural changes after 5 days of treatment. The number of luteotroph (LTH) cells is signficantly increased; they display characteristics of stimulation. The extrusion of granules into the intercellular space via exocytosis is frequently observed. The intercellular spaces are highly dilated, forming a lacunar system filled with an amorphous material, erythrocytes and involuted LTH cells. Transitional stages in the process of involution are observed in LTH cells. Luteotroph cells also form a syncytium. Twenty days after treatment the above-described changes decrease in magnitude. The present findings suggest that pimozide stimulates the mechanism of synthesis and release in the luteotroph cells, an effect that is less evident with longer treatment.


Ultrastructure of the articular cartilage of the mandibular condyle: aging and degeneration.
To obtain more insight into the pathogenesis of osteoarthrosis of the temporomandibular joint, we examined the ultrastructure of articular cartilage of six healthy and sixteen osteoarthrotic human mandibular condyles. Ultrastructural changes due to aging and osteoarthrosis are described and compared with the findings of other ultrastructural studies of articular cartilage of synovial joints. Aging was accompanied by some slight degenerative signs. Osteoarthrotic hyaline cartilage and fibrocartilage showed a striking similarity. The only ultrastructural difference was the presence of elastic fibers in the latter. Therefore, both seem to have the same pathogenesis. Several current statements on the pathogenesis of osteoarthrosis are discussed.


Habitat-specific environmental factors regulate the spatial variability of biological soil crust microbial communities on the Qinghai-Tibet Plateau.
Biological soil crusts (BSCs) are an important biological component of the soil surface, covering approximately 12 % of the Earth's land surface. Although BSCs are closely related to habitats, the microbial diversity and spatial variability of BSCs in different ecosystems are still unclear, especially on the Qinghai-Tibet Plateau (QTP), where climate is changeable and habitats are complex. Here, we investigated the diversity, assembly processes, spatial distribution pattern and driving factors of prokaryotic and eukaryotic microbial communities in BSCs in four habitats on the QTP. It was found that habitat-specific environmental factors regulated the composition, diversity and spatial variability of BSC microbial communities. Soil organic carbon and soil water content were the most important factors (R2 = 0.9024, P = 0.001; R2 = 0.8004, P = 0.001) affecting the spatial differences in prokaryotes and eukaryotes, respectively. Under the specific climate of the QTP, the spatial pattern of microbial communities in BSCs was controlled by precipitation rather than temperature. In addition, ecological processes further explained the effects of habitat specificity, and environmental filtering explained microbial community differences better than dispersal limitation. The results of the neutral community model and the normalized stochastic ratio index revealed that the assembly of prokaryotic communities was determined by deterministic processes at the regional scale, and at the local scale, the assembly process was mainly determined by habitat type, while the assembly of eukaryotic communities was determined by stochastic processes at both the regional and local scales. This study provided a scientific reference for the prediction of BSC distribution and resource conservation under future climate change scenarios.


Prognostic value of right ventricular strain and peak oxygen consumption in heart failure with reduced ejection fraction.
Our purpose is to evaluate the combined predictive value of cardiopulmonary exercise testing (CPET) and echocardiographic evidence of left ventricular (LV) and right ventricular (RV) strain in predicting mortality and heart transplant (HTx) in a series of outpatients with heart failure with reduced ejection fraction (HFrEF). A retrospective cohort study of 66 patients with HFrEF (median age, 57 years; 51% women) who underwent CPET and echocardiography (up to 90 days apart) to assess prognosis. The primary outcome was a composite of death and need for HTx. At a median follow-up of 27 [20-39] months, 19 patients (29%) experienced the primary outcome. In unadjusted analysis, most echocardiographic and CPET parameters were associated with the primary outcome, including percentage of predicted peak oxygen consumption (ppVO2), VE/VCO2 slope, LV ejection fraction, and LV and RV longitudinal strain. After adjusting for other clinical, echocardiographic and CPET variables, RV free wall longitudinal strain and ppVO2 remained significantly associated with the primary outcome. Kaplan-Meier survival curves for death and HTx, based on the best cutoff values, showed lower survival rates in patients with impairment in both ppVO2 and RV FW-LS than in those with one or neither parameter impaired (p < 0.001). RV dysfunction and low cardiorespiratory fitness were independent markers of death and need for HTx. Impairment of both ppVO2 and RV FW-LS had a strong additive impact on prognostic assessment in this cohort of patients with HFrEF.


Enhancement of trehalose production in dairy propionibacteria through manipulation of environmental conditions.
We have shown that the ability to produce trehalose is widespread within the genus Propionibacterium. Eighteen strains isolated from dairy sources were screened for trehalose synthesis; the effect of environmental conditions on trehalose production was evaluated in Propionibacterium freudenreichii ssp. shermanii NIZO B365, a strain that accumulated high amounts of this disaccharide. Lactose was the best carbohydrate source for trehalose production, whereas lactate, the substrate that led to the highest specific growth rate, was a poor precursor. Trehalose was consumed after exhaustion of the carbon source in the medium, suggesting its role as a reserve compound. The production of trehalose was not affected by lowering the growth temperature from 30 to 20 degrees C. On the other hand, the maximum trehalose accumulation increased from about 200 to 400 mg of trehalose/g of cell protein upon decreasing the pH from 7.0 to 4.7, by increasing the concentration of NaCl to 2% (w/v), or during growth under aerobic conditions (50% air saturation, 24 microM O(2), pH 7.0). In the absence of NaCl, trehalose accumulated concomitantly with growth, but an increase in salinity triggered a high trehalose production already in the early exponential growth phase. The data provide evidence for a dual function of trehalose as a reserve compound and as a stress-response metabolite. Moreover, P. freudenreichii ssp. shermanii NIZO B365 was able to produce high levels of trehalose in skim milk, which is promising for the implementation of fermented dairy products.


Burkholderia cepacia complex in cystic fibrosis in a Brazilian reference center.
The Burkholderia cepacia complex (BCC) can cause a severe decline in lung function in cystic fibrosis (CF). Our objective was to determine the BCC prevalence and to evaluate its clinical impact on CF. Clinical and laboratory variables were determined for CF patients with BCC (Group-A = 50 patients) and without BCC (Group-B = 134 patients). The microorganisms were identified by biochemical tests, the Vitek2®Compact test, recA-PCR and recA-nested-PCR with species-specific primers and DNA sequencing. The patients were evaluated by the Shwachman-Kulczycki score (SKCS), Bhalla score (BS), spirometry and body mass index (BMI). The BCC prevalence was 22.5%. The most common species were Burkholderia multivorans (30%), Burkholderia cepacia (24%), Burkholderia cenocepacia IIIA (10%), B. cenocepacia IIIB (2%) and Burkholderia vietnamiensis (2%). There was difference between the groups in nutritional status (p = 0.02) and general activity (p = 0.026). There was difference in total BS points (p = 0.04) and the following parameters: bronchiectasis severity (p = 0.007), peribronchial thickening (p = 0.013), bronchiectasis extent (p = 0.01) and general aspects of the affected bronchial zone (p = 0.02). The respiratory disorder classifications were as follows: obstructive-4.8% (Group-A) and 23.8% (Group-B); restrictive-9.5% (Group-A and Group-B); obstructive + restrictive-19% (Group-A) and 1.6% (Group-B); and obstructive + restrictive with a decreased forced expiratory flow-47.6% (Group-A) and 30.2% (Group-B) (p = 0.02). Nutritional status was a minor contributing factor to weight, height and BMI in the Group-A (p = 0.02). The BCC prevalence, particularly the prevalence of B. multivorans, was higher in this study. The SKCS, BS, spirometry and nutritional status results showed that BCC has a negative impact on clinical status. Phenotypic methods are useful for the identification of presumptive BCC. The Vitek2®Compact test showed accuracy in BCC identification. PCR, nested-PCR, and recA sequencing showed specificity in BCC species identification.


Corrigendum: Whole-genome sequencing provides insight into antimicrobial resistance and molecular characteristics of Salmonella from livestock meat and diarrhea patient in Hanzhong, China.
[This corrects the article DOI: 10.3389/fmicb.2022.899024.].


Cognitive slippage and depression in hypothetically psychosis-prone college students.
Subjects who scored deviantly high on the combined Perceptual Aberration-Magical Ideation (Per-Mag) Scale and subjects who scored low on the scale were compared on two putative measures of cognitive slippage--a continued word association task and a task of referential communication. The Per-Mag subjects performed more deviantly than did the control subjects on both tasks, but those Per-Mag subjects who also scored above the mean on the General Behavior Inventory (GBI) depression subscale were most deviant. The Per-Mag Scale and the GBI are recommended for concurrent use in mass screening to identify a group of individuals who exhibit signs of cognitive slippage and who may, therefore, be at risk for the development of severe psychopathology.


A novel diphospho-P,P'-diester from Methanobacterium thermoautotrophicum.
A phosphorus-containing metabolite that accounts for up to 80% of the total phosphate in perchloric acid extracts of Methanobacterium thermoautotrophicum ATCC 29183 was purified by chromatography on an anion exchange column. The proton-decoupled 31P NMR spectrum of the sodium salt in D2O exhibits an AB quartet with lines at -9.48, -9.78, -10.78, and -11.08 ppm upfield from 85% phosphoric acid. The phosphorus-phosphorus coupling constant is 18.5 Hz, a value characteristic of a pyrophosphate linkage. The structure of this compound has been tentatively established as cyclic-2,3-diphosphoglycerate (Kanodia, S., and Roberts, M. F. (1983) Proc. Natl. Acad. Sci. U.S.A., in press). Although rapidly degraded in neutral cell extracts, the diphosphodiester was stable for hours in cells whose metabolism had been arrested by depletion of H2 from the medium. If the cells were transferred to phosphate-free medium in the presence of H2 and CO2, the diester disappeared in about one cell generation. These findings point to a possible role as a phosphate storage compound, but the real function(s) of this unusual diphosphodiester must await a complete analysis of its structure and further metabolic studies.


Health Professionals' Attitudes and Beliefs About Breastfeeding.
The aim of this descriptive study was to investigate how health-care providers perceived their role in breastfeeding and maternal support. Data was collected via interviews of 53 health-care professionals that provided care to breastfeeding women. The emerging themes included (a) understanding the benefits of breastfeeding: often lacking current knowledge, (b) lacking consistency: gaps between knowledge of benefits and actual clinical practice, (c) not knowing how to help: lack of assessment and therapeutic skills, and (d) understanding the barriers to breastfeeding: how health-care providers can make a difference. Data analysis suggests inconsistencies between the health-care provider's perceived support and behaviors, lack of knowledge, and significant lack of skill in the assessment and management of breastfeeding couples.


Encouraging self-care within a primary health care framework.
This study was undertaken primarily to evaluate Do I Need to See the Doctor?, a book designed to assist young families to self-manage common health problems. In addition, the study sought to determine whether providing an introductory explanation to the book had an impact on the respondents' perceived usefulness of it. Comparisons of emergency room visits were made for the timeframe of the study and for the previous year. Study results support the book's usefulness in increasing respondents' confidence to make knowledgeable, informed self-care decisions. Providing explanations did not affect the book's usefulness. A link between emergency room visits and the book requires further study.


Experiences with a psychosocial screening instrument (S-FIRST) to identify the psychosocial support needs of parents of children suffering from cancer.
A large proportion of families with a child suffering from cancer are heavily burdened, both psychologically and socially functions, thus requiring treatment. Therefore, a systematic assessment of burden and needs is essential to identify clients with a high psychosocial burden and to allow for accurate decision making regarding indications for treatment. There is a great need for the development and validation of screening instruments in psychosocial counseling. The receiver operating characteristic curve is a basic method to evaluate the discriminatory power of diagnostic tests. We computed sensitivity/specificity indices based on a sample of parents of pediatric cancer patients; the parents were screened with the S-FIRST and completed another standardized instrument with reliable indicators. We found significant area under the curve (AUC) values from 0.671 to 0.882, meaning that the S-FIRST screening instrument has small to medium discriminatory power. Our results support the use of a screening instrument for case history analyses in psychosocial counseling to identify clients with a high psychosocial burden.


Exercise, performance and temperature control: temperature regulation during exercise and implications for sports performance and training.
Thermoregulation is an important consideration not only for athletic performance but also for the safety of the athlete. This article presents a broad overview of the mechanisms by which body heat is dissipated in an individual exercising in a hot environment. Particularly emphasised are more recent views of body heat loss mechanisms and the influences of non-thermal inputs, such as effects due to changing blood volume or blood flow distribution. During exercise in a hot environment, metabolic heat produced by the exercising muscles is transported by the circulating blood to the surface of the body where it is released to the environment, either by radiation and convection or by evaporation of sweat. The primary drives for both the increased skin blood flow and increased body sweating are the thermal inputs which are sensed by receptors in the deep body core, with a lesser drive from skin receptors. These thermal signals are integrated in the hypothalamus and proper heat loss responses are effected. When exercise is prolonged, however, and body rehydration is not adequate, the total blood volume may be compromised. In addition, as the core temperature increases during exercise, larger proportions of the blood volume are distributed to the cutaneous vessels, thus effectively reducing cardiac return and central blood volume. During severe exercise, a reduction in cardiac filling may result in a fall in central venous pressure and stimulate baroreceptor vasoconstrictor reflexes. As discussed below, the outputs from these baroreceptors compete with and modify the thermal drives for both the control of the skin blood flow and control of the sweat glands. The effect of high ambient temperatures on exercise performance is most evident in prolonged submaximal exercise. Normally, maximal exercise performance is not altered by high temperatures unless the individual has an elevated deep body temperature before the start of the exercise task. However, submaximal exercise performance is often impaired by high ambient temperatures, but may be improved by programmes of physical training and heat acclimatisation. Both training and heat acclimatisation significantly modify the control systems which regulate skin blood flow and sweating. Only acclimatisation programmes, however, are effective in preventing heat stress during prolonged exercise in hot environments.


Molecular dynamics simulations of the periplasmic ferric-hydroxamate binding protein FhuD.
FhuD is a periplasmic binding protein (PBP) that, under iron-limiting conditions, transports various hydroxamate-type siderophores from the outer membrane receptor (FhuA) to the inner membrane ATP-binding cassette transporter (FhuBC). Unlike many other PBPs, FhuD possesses two independently folded domains that are connected by an alpha-helix rather than two or three central beta-strands. Crystal structures of FhuD with and without bound gallichrome have provided some insight into the mechanism of siderophore binding as well as suggested a potential mechanism for FhuD binding to FhuB. Since the alpha-helix connecting the two domains imposes greater rigidity on the structure relative to the beta-strands in other 'classical' PBPs, these structures reveal no large conformational change upon binding a hydroxamate-type siderophore. Therefore, it is difficult to explain how the inner membrane transporter FhuB can distinguish between ferrichrome-bound and ferrichrome-free FhuD. In the current study, we have employed a 30 ns molecular dynamics simulation of FhuD with its bound siderophore removed to explore the dynamic behavior of FhuD in the substrate-free state. The MD simulation suggests that FhuD is somewhat dynamic with a C-terminal domain closure of 6 degrees upon release of its siderophore. This relatively large motion suggests differences that would allow FhuB to distinguish between ferrichrome-bound and ferrichrome-free FhuD.


Comprehensive assessments of long-term sleep habits in epidemiological study: Validity and reliability of sleep factors questionnaire (SFQ) among Chinese women.
Epidemiological studies suggested that poor sleep is a potentially novel risk factor for several health outcomes currently; however, there are no validated questionnaires that can systematically measure sleep parameters within these studies. We evaluated the reliability and validity of 17-item sleep factors questionnaire (SFQ), which was developed to comprehensively assess long-term sleep habits for the Jiujiang Breast Cancer Study (JBCS), Jiujiang, China. The participants included 100 women aged 18-74years, who were randomly selected from the JBCS project, and completed a SFQ at baseline and again 1year later, and 4 quarterly 30 consecutive days (a total of 120days) sleep diaries over this same year. Reliability was tested by comparing the 2 SFQs; validity by comparing the average measures between the SFQ and the 4 sleep diaries. Validity analysis showed moderate correlation (γ=0.41) for sleep duration with the adjusted concordance correlation coefficient (CCCadj) of 0.54; the weighted κ statistics indicated an excellent agreement for night/shift work and sleep medication use; fair-to-moderate for sleep quality, light at night (LAN), nighttime sleeping with light on, sleep noise and nap time; slight-to-fair for sleep quality and nighttime wakings frequency. Reliability analysis showed excellent correlation for night/shift work and sleep medication use; fair-to-moderate for LAN, nighttime wakings frequency, insomnia frequency, sleep noise and nap time; but slight-to-fair for insomnia frequency and nighttime sleeping with light on; the CCCadj for sleep duration was 0.61. The SFQ showed reasonable reliability and validity for sleep assessments in most domains.


Peripheral oxytocin injection modulates vomeronasal sensory activity and reduces pup-directed aggression in male mice.
Behaviors are shaped by hormones, which may act either by changing brain circuits or by modifying sensory detection of relevant cues. Pup-directed behaviors have been previously shown to change via action of hormones at the brain level. Here, we investigated hormonal control of pup-induced activity in the vomeronasal organ, an olfactory sensory structure involved in the detection of non-volatile chemosignals. Vomeronasal activity decreases as males switch from a pup-aggressive state to a non-aggressive parenting state, after they socially contact a female. RNA sequencing, qPCR, and in situ hybridization were used to identify expression, in the vomeronasal sensory epithelium, of candidate GPCR hormone receptors chosen by in silico analyses and educated guesses. After identifying that oxytocin and vasopressin receptors are expressed in the vomeronasal organ, we injected the corresponding hormones in mice and showed that oxytocin administration reduced both pup-induced vomeronasal activity and aggressive behavior. Conversely, injection of an oxytocin receptor antagonist in female-primed male animals, which normally exhibit reduced vomeronasal activity, significantly increased the number of active vomeronasal neurons. These data link oxytocin to the modulation of olfactory sensory activity, providing a possible mechanism for changes in male behavior after social experience with females.


Comparative sensitivity of intracoronary injection of acetylcholine for the induction of coronary spasm in patients with various types of angina pectoris.
To elucidate the possible contribution of coronary artery spasm to the pathogenesis of angina pectoris, coronary arterial responses to intracoronary injection of acetylcholine were examined in patients with various types of angina pectoris. Coronary artery spasm with chest pain and/or electrocardiographic ischemic changes was angiographically demonstrated in 50 (85%) of 59 patients with angina pectoris. The sensitivity for coronary spasm was 92% (24 of 26) in patients with rest angina, 100% (16 of 16) in patients with both rest and effort angina, and 59% (10 of 17) in patients with effort angina, while it was only 6% (1 of 16) in patients without coronary artery disease. When patients with effort angina were subdivided according to the variability of anginal threshold for exertional angina, the sensitivity for coronary spasm was as high as 90% (9 out of 10) in patients with variable-threshold angina. In contrast, coronary spasm was less frequently (p less than 0.05) induced in patients with fixed-threshold angina (1 of 7, 14%). These results suggest that coronary arteries in patients with angina pectoris are quite susceptible to acetylcholine except in those patients with stable exercise tolerance or anginal threshold. Thus coronary artery spasm appears to play a significant role for the pathogenesis of angina pectoris in a large proportion of patients with effort angina as well as in patients with rest angina.


Genetic analysis of growth curve in Moghani Sheep using Bayesian and restricted maximum likelihood.
This study was conducted to predict the genetic (co)variance components of growth curve parameters of Moghani sheep breed using the following information: birth weight (N = 7278), 3-mo-old weight (N = 5881), 6-mo-old weight (N = 5013), 9-mo-old weigh (N = 2819], and 12-mo-old weight (N = 2883). The growth parameters (A: maturity weight, B: growth rate, and K: maturity rate) were calculated using Gompertz, Logistic, Brody, and Von Bertalanffy nonlinear models via NLIN procedure of SAS software. The aforementioned models were compared using Akaike information criterion, root mean square error, adjusted co-efficient of determination. Also, both Bayesian (using MTGSAM) and RMEL (using WOMBAT) paradigms were adapted to predict the genetic (co)variance components of growth parameters (A, B, K) due to the best fitted growth models. It was turned out that Von Bertalanffy best fitted to the data in this study. The year of birth and lamb gender had a significant effect on maturity rate (P < 0.01). Also it turned out that within the growth parameter, with increasing (co)variance matrix complexity, the Bayesian paradigm fitted well to the data than the restricted maximum likelihood (REML) one. However, for simple animal model and across all growth parameters, REML outperformed Bayesian. In this way, the h2a predicted (0.15 ± 0.05), (0.11±.05), and (0.04 ± 0.03) for A, B, and K parameters, respectively. Practically, in terms of breeding plan, we could see that genetic improvement of growth parameters in this study is not a tractable strategy to follow up and improvement of the management and environment should be thoroughly considered. In terms of paradigm comparison, REML's bias correction bears up an advantageous approach as far as we are concerned with small sample size. To this end, REML predictions are fairly accurate but the mode of posterior distributions could be overestimated. Finally, the differences between REML and Bayesian estimates were found for all parameter data in this study. We conclude that simulation studies are necessary in order to trade off these parading in the complex random effects scenarios of genetic individual model.


Imaging in pediatric ovarian tumors.
The spectrum of ovarian tumors in the pediatric population differs significantly from that in adults. Germ cell tumors are the predominant class of ovarian tumors in children, whereas epithelial tumors are the most common in adults. Ultrasonography is the modality of choice for the initial evaluation of pediatric ovarian tumors. Determining the diagnosis based on imaging may prove difficult, and combining the imaging findings with the clinical scenario is very helpful in reaching a differential diagnosis during clinical practice. We will discuss the spectrum of ovarian neoplasms in the pediatric population and describe their clinical, pathologic, and imaging characteristics. A few unique entities related to ovarian tumors, such as growing teratoma syndrome, anti-N-methyl-D-aspartate receptor encephalitis, and hereditary ovarian tumor syndromes, are also discussed. In addition, we will review several entities that may mimic ovarian neoplasms as well as their distinct imaging features.


Muscle sympathetic vasoconstrictor activity in hydrocortisone-induced hypertension in humans.
This study was undertaken to test the hypothesis that increased sympathetic vasomotor drive is responsible for cortisol-induced hypertension. Ten healthy male subjects on a fixed sodium diet (150 mmol/day) were randomized to five days of treatment with cortisol (200 mg/day) or placebo in a double-blind crossover study. On day 5 of each treatment, multi-unit muscle sympathetic activity was recorded from the common peroneal nerve. Resting muscle sympathetic activity (MSA) was measured in the recumbent position and stimulated MSA was measured in the final 20 sec of end-inspiratory capacity apnoea and end-expiratory apnoea and in the second minute of a cold pressor stimulus. A subgroup of six subjects also underwent identical MSA measurements following 5 days treatment with dexamethasone (3 mg/day). Cortisol, but not placebo, significantly increased systolic (115+/-2 vs 129+/-3 mmHg precortisol vs cortisol day 5, p < 0.001) and diastolic blood pressure (53+/-3 vs 61+/-3, p < 0.05). Resting MSA was significantly reduced by cortisol (23.9+/-2.3 to 5.0+/-2.0 bursts/min, placebo vs cortisol, p < 0.01). Cortisol significantly attenuated the increase in MSA observed at end-inspiratory apnoea (56.3+/-3.9 vs 35.4+/-6.6, p < 0.05) and end-expiratory apnoea (50.5+/-3.5 vs 26.3+/-6.2 bursts/min, n = 8, p < 0.05), and during the cold pressor response (55.0+/-12.7 vs 21.4+/-7.6, n = 5, p < 0.05). Dexamethasone significantly increased systolic blood pressure and suppressed resting and stimulated MSA. No changes in body weight, haematocrit or angiotensin II concentrations occurred during dexamethasone treatment. MSA is significantly suppressed by cortisol treatment. As suppression of MSA is also observed during treatment with the pure glucocorticoid dexamethasone, suppressed MSA cannot be attributed to increased plasma volume or to changes in angiotensin II concentration. We conclude that cortisol-induced hypertension is not due to increased muscle sympathetic vasomotor drive.


Commentary on EPA carcinogen risk assessment guidelines.
EPA has indicated the Agency's Cancer Risk Assessment Guidelines are intended to be evergreen, i.e., subject to revision as advances are made in scientific understanding or difficulties are encountered. Several changes could be made in the Guidelines to better utilize advances in science, some of which EPA has already incorporated into risk assessment procedures, and also to alleviate difficulties encountered by the Agency. The hazard identification step of risk assessment should be more clearly defined, especially with respect to describing the best use of animal data to predict human hazard. The classification system for summarizing carcinogenic hazard should be expanded, and the titles revised, to better describe the varying degrees of knowledge concerning human carcinogenic hazard derived from experimental data. Current dose response estimation procedures should be supplemented to provide risk managers more perspective on human risk. Suggested additions are a central estimate of the upper bound of the dose response curve and a most plausible estimate of human response as a function of dose. The central estimate of the upper bound still includes the calculation of a statistical upper limit, but utilizes central estimates for some of the critical policy options. The most plausible estimate relies heavily on evaluation of the mechanism of carcinogenic activity and its implications for dose response estimation in humans. Thus, the outcome of dose response evaluation would include the current upper bound (worst case), a more central estimate of the upper bound, a most plausible estimate, and the lower bound.


Sarcoidosis affecting the periodontium: a long-term follow-up case.
Clinical manifestations of sarcoidosis affecting the periodontium could mimic aggressive periodontitis. This case report documents the occurrence of sarcoidosis affecting the periodontium, including its clinical features, diagnosis, treatment, and 6-year follow-up. An individual with a history of pulmonary sarcoidosis was referred for evaluation and treatment of an aggressive periodontal condition. Clinical, radiographic, and histopathologic findings supported the diagnosis of sarcoidosis affecting the periodontium. Initial treatment consisted of reinforcement of oral hygiene, scaling and root planing, chlorhexidine rinses, and periodontal maintenance. The systemic disease was managed with prednisone, alendronate, and losartan. Twelve months later, the patient returned with severe attachment loss of sudden onset and gingival recession affecting the facial right surfaces of maxillary posterior teeth. In addition, he complained of chronic pain of moderate to severe intensity involving both jaws. The affected teeth were extracted and the surrounding alveolar bone was debrided. Intraoral sarcoidosis was confirmed by histologic findings, and his medications were changed to methotrexate and hydroxychloroquine. The patient has been followed for 6 years with continuation of the systemic medications and periodontal maintenance every 3 to 4 months without recurrence of intraoral sarcoidosis. The main features of this unique periodontal presentation were pain, rapidly progressive gingival recession, and significant changes in alveolar bone density in focal areas. Careful review of medical history and close monitoring of intraoral conditions are critical for patients with a history of sarcoidosis. An intraoral biopsy is necessary to confirm a definitive diagnosis in cases with similar clinical findings.


Antiulcer activity of Salvadora persica L.: structural modifications.
In previous work we observed that the decoction of Salvadora persica L. possessed significant protective action against ethanol and stress-induced ulcers. This study was designed to confirm the antiulcer activity of Salvadora persica decoction using optical microscopy. The elements of gastric mucosa tended to be reestablished normally in treated rats.


Alterations in myocardial gene expression associated with experimental Trypanosoma cruzi infection.
Chagas disease, characterized by acute myocarditis and chronic cardiomyopathy, is caused by infection with the protozoan parasite Trypanosoma cruzi. We sought to identify genes altered during the development of parasite-induced cardiomyopathy. Microarrays containing 27,400 sequence-verified mouse cDNAs were used to analyze global gene expression changes in the myocardium of a murine model of chagasic cardiomyopathy. Changes in gene expression were determined as the acute stage of infection developed into the chronic stage. This analysis was performed on the hearts of male CD-1 mice infected with trypomastigotes of T. cruzi (Brazil strain). At each interval we compared infected and uninfected mice and confirmed the microarray data with dye reversal. We identified eight distinct categories of mRNAs that were differentially regulated during infection and identified dysregulation of several key genes. These data may provide insight into the pathogenesis of chagasic cardiomyopathy and provide new targets for intervention.


Deuterium and oxygen-18 measurements on microliter samples of urine, plasma, saliva, and human milk.
Improved methods to measure 2H:1H and 18O:16O isotope ratios on microliter samples of biological fluids are described. Enriched levels of 2H (580%) and 18O (256%) in urine, plasma, saliva, and human milk can be measured with a precision of 3.2% (n = 200) and 0.97% (n = 200) and an accuracy of -4.6 +/- 4.4% (mean +/- SD, n = 200) and -0.32 +/- 0.87% (mean +/- SD, n = 200), respectively. Hydrogen gas samples are generated from 10 microL of undistilled fluid by zinc reduction in quartz reaction vessels. Water-CO2 equilibration of a 100-microL sample for 18O measurement is completed in 10 h using a modified commercial equilibration system. These methodological improvements facilitate and extend the use of 2H and 18O tracers in studies of body composition and energy expenditure.


Influence of material composition on the morphology and engineering properties of waste plastic binder composite for construction purposes.
Ways of mitigating the menace caused by the abundance of waste plastic generated have been a global concern. Efforts are geared towards intensification of the recycling culture for circular economy. Recent studies combined waste plastic and sand to make Waste Plastic Binder (WPB) composite materials. However, sand mining operation has been associated with environmental and ecological issues. This study explores the engineering properties of waste plastic and quarry dust composite for sustainable infrastructural development. The polyethylene terephthalate type of plastic (PET) was employed, and which was melted and mixed with QD at different compositions of 1:0, 1:1, 1:2, and 1:3 respectively. The influence of the varying compositions on the morphological and engineering properties of resulting WPB composite was investigated. The scanning electron microscopy image showed that WPB composite with higher percentage of QD possess lesser pore space, and which influenced the high strength values. The findings showed P&QD 1:3 have highest compressive strength value of 20.1MPa, and which meets up with the American Concrete Institute and South African standard minimum requirement of 17MPa for structural lightweight concrete applicable for walkways, walling and water retaining structures constructions.


Differences in preterm and term milk fatty acid compositions may be caused by the different hormonal milieu of early parturition.
The hormonal milieus of pregnancy and lactation are driving forces of nutrient fluxes supporting infant growth and development. The decrease of insulin sensitivity with compensatory hyperinsulinemia with advancing gestation, causes adipose tissue lipolysis and hepatic de novo lipogenesis (DNL). We compared fatty acid (FA) contents and FA-indices for enzyme activities between preterm (28-36 weeks) and term (37-42) milks, and between colostrum (2-5 days), transitional (6-15) and mature (16-56) milks. We interpreted FA differences between preterm and term milks, and their changes with lactation, in terms of the well known decrease of insulin sensitivity during gestation and its subsequent postpartum restoration, respectively. Compared with term colostrum, preterm colostrum contained higher indices of DNL in the breast (DNL-breast) and medium chain saturated-FA (MCSAFA), and lower DNL-liver and monounsaturated-FA (MUFA). Preterm milk also had higher docosahexaenoic acid (DHA) in colostrum and transitional milk and higher arachidonic acid (AA) in mature milk. Most preterm-term differences vanished with advancing lactation. In both preterm and term milks, DNL-breast and MCSAFA increased with advancing lactation, while DNL-liver, MUFA, long chain SAFA and AA decreased. DHA decreased in term milk. MUFA was inversely related to MCSAFA in all samples, correlated inversely with PUFA in colostrum and transitional milks, but positively in mature milk. MCSAFA correlated inversely with PUFA in mature milk. Higher maternal insulin sensitivity at preterm birth may be the cause of lower MUFA (a proxy for DNL-liver) and higher MCSAFA (a proxy for DNL-breast) in preterm colostrum, compared with term colostrum. Restoring insulin sensitivity after delivery may be an important driving force for milk FA-changes in early lactation.


[A method for removing moiré artifacts from scanned images of radiochromic films: application to transmissive scanning].
Dose verification using radiochromic films may bring about moiré artifacts during the film scanning process using a flatbed scanner. A method for removing the moiré artifacts was already reported for reflective scanning. Recently, transmissive scanning using EBT2 films has played a major role for dose verification in intensity-modulated radiation therapy. It was found that placing a nonreflecting glass plate on the detector side could eliminate all the moiré artifacts for transmissive scanning.


Response to "Letter to the editor re: Cheng YH, Chou WC, Yang YF, et al. Environ Sci Pollut Res (2018). https://doi.org/10.107/s11356-017-0875-4".


Feed rations fed by US dairy producers.
Feed rations used by US dairy producers are estimated using data from the USDA Agricultural Resource Management Survey. The 2016 dairy version of the survey was used, in which 955 respondents fully responded on feed usage. Surveyed farms milked ≥10 cows and were located in dairy states that together produced 96.5% of milk in the United States. Average feedstuff usage is estimated at the national level, as well as regional, production system, and farm size category levels. Significance of differences in feedstuff usage among the categories are determined using t-tests derived using the delete-a-group jackknife procedure. Results are compared with published university feed cost estimates. Differences in feedstuff usage are found by region, production system, and farm size categories.


Outcome of the treatment of osteonecrosis of femoral head using the core decompression with bone impaction grafting.
To evaluate the outcome of core decompression with bone impaction grafting for the treatment of osteonecrosis of femoral head. Totally 39 cases (46 hips) of osteonecrosis of femoral head were treated with core decompression and impaction bone grafting. According to the Association Research Circulation Osseous (ARCO) system, 3 hips were graded for stage 1,16 for stage 2a,7 for 2b,11 for 2c, and 9 for 3.The Harris hip score (HHS) was evaluated before operation and at the latest follow-up. In all these patients, 22 hips had hormone-related lesions, 11 had alcohol-related lesions, and 13 had idiopathic lesions. The average HHS was changed from (66 ± 6.6) before surgery to (80.2 ± 9.7) after surgery during an average follow-up of 26 months(from 9 to 48 months). The postoperative HHS showed no significant difference among osteonecrosis of femoral head due to different etiologies.Also,the postoperative HHS and clinical effectiveness were not significantly different among patients with different preoperative stages.The postoperative outcome was excellent in 7 cases, good in 23 cases, mild in 4 cases,and poor in 12 cases. The rate of excellent and good was 65% in this series,with 78% for patients with early stages and 52.6% for those with grade 2c or higher lesions. The femoral head collapsed in 7 cases,and 5 of which were preoperatively graded as in stage 2c and higher. The postoperative complications included intertrochanteric fracture (n=1) and infection (n=1). Four hips were converted to total hip arthroplasty. All of other hips had no obvious progression of osteonecrosis. Core decompression with bone impaction allografting is effective for the treatment of osteonecrosis of femoral head. Patients with lesions in earlier ARCO stages can have better outcomes.


[Systematic neonatal screening for Duchenne muscular dystrophy].
More than 15% of cases of Duchenne muscular dystrophy (DMD) may be preventable by the neonatal diagnosis of another affected relative. Systematic neonatal screening seems a more efficient way of getting information for genetic counseling. The principle of the test described is the detection of a specific increase of the activity of Creatine-Kinase (CK) in the blood of newborn children with myopathy. Blood may be spotted on paper and posted to a central laboratory. Furthermore this program can be integrated into the systematic screening of phenylketonurie. The specificity and accuracy of the bioluminescent reaction used for the evaluation of CK suggest that this screening reaction is reliable. A systematic neonatal screening program for DMD such as ours in the Rhône-Alpes area (France) will lead to frequent recourse to prenatal diagnosis now possible through sex fetal determination and which would be possible through in utero blood sampling.


An alternative aesthetic restoration for extensive coronal destruction in primary molars: indirect restorative technique with composite resin.
The indirect restorative technique with composite resin has presented efficient results when used in primary teeth. This technique enables the oral rehabilitation. Based on the results presented in the literature concerning clinical performance, this technique is presented as an alternative treatment to the primary teeth with extensive decay by showing a case of rehabilitation of primary molars. The oral rehabilitation using indirect resin composite restoration showed an important concept to be applied in primary dentition due to feasible, low cost, and lower chairside time.


Introns Structure Patterns of Variation in Nucleotide Composition in Arabidopsis thaliana and Rice Protein-Coding Genes.
Plant genomes present a continuous range of variation in nucleotide composition (G + C content). In coding regions, G + C-poor species tend to have unimodal distributions of G + C content among genes within genomes and slight 5'-3' gradients along genes. In contrast, G + C-rich species display bimodal distributions of G + C content among genes and steep 5'-3' decreasing gradients along genes. The causes of these peculiar patterns are still poorly understood. Within two species (Arabidopsis thaliana and rice), each representative of one side of the continuum, we studied the consequences of intron presence on coding region and intron G + C content at different scales. By properly taking intron structure into account, we showed that, in both species, intron presence is associated with step changes in nucleotide, codon, and amino acid composition. This suggests that introns have a barrier effect structuring G + C content along genes and that previous continuous characterizations of the 5'-3' gradients were artifactual. In external gene regions (located upstream first or downstream last introns), species-specific factors, such as GC-biased gene conversion, are shaping G + C content whereas in internal gene regions (surrounded by introns), G + C content is likely constrained to remain within a range common to both species.


Anisotropic Properties of Polylactic acid⁻carbon Fiber Composites Prepared by Droplet spray Additive Manufacturing.
Anisotropic materials are important functional materials in many fields. The use of these materials is currently being expanded through the rapid development of additive manufacturing. However, there is still no universal method for fabricating two-dimensional anisotropic polymer composites. Here, polylactic acid⁻carbon fiber composites were prepared using the droplet spray method, and their mechanical and friction properties were studied. The tensile strength in the X⁻Y plane perpendicular to the direction of the droplet spray was significantly higher than that in the direction of droplet ejection. Similar trends were observed for the elongation at breaking and the impact strength. The friction coefficient was smallest in the X⁻Y plane. Scanning electron microscopy showed that carbon fibers were oriented in the X⁻Y plane, which enhanced the mechanical and friction properties in this plane.


Studying antibiotic persistence in vivo using the model organism Salmonella Typhimurium.
Antibiotic persistence permits a subpopulation of susceptible bacteria to survive lethal concentrations of bactericidal antibiotics. This prolongs antibiotic therapy, promotes the evolution of antibiotic-resistant pathogen strains and can select for pathogen virulence within infected hosts. Here, we review the literature exploring antibiotic persistence in vivo, and describe the consequences of recalcitrant subpopulations, with a focus on studies using the model pathogen Salmonella Typhimurium. In vitro studies have established a concise set of features distinguishing true persisters from other forms of bacterial recalcitrance to bactericidal antibiotics. We discuss how animal infection models are useful for exploring these features in vivo, and describe how technical challenges can sometimes prevent the conclusive identification of true antibiotic persistence within infected hosts. We propose using two complementary working definitions for studying antibiotic persistence in vivo: the strict definition for studying the mechanisms of persister formation, and an operative definition for functional studies assessing the links between invasive virulence and persistence as well as the consequences for horizontal gene transfer, or the emergence of antibiotic-resistant mutants. This operative definition will enable further study of how antibiotic persisters arise in vivo, and of how surviving populations contribute to diverse downstream effects such as pathogen transmission, horizontal gene transfer and the evolution of virulence and antibiotic resistance. Ultimately, such studies will help to improve therapeutic control of antibiotic- recalcitrant populations.


Intestinal tumor progression is promoted by decreased apoptosis and dysregulated Wnt signaling in Ceacam1-/- mice.
The carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is downregulated in colonic and intestinal hyperplastic lesions as well as in other cancers, where it functions as a tumor suppressor. To investigate the functions of CEACAM1 in the normal intestine and in intestinal tumors, we generated a compound knockout mouse model and examined both Ceacam1(-/-) and Apc(1638N/+):Ceacam1(-/-) mice. Ceacam1(-/-) intestinal cells exhibited a significant decrease in apoptosis, with no change in proliferation or migration, however. Compound Apc(1638N/+):Ceacam1(-/-) mice demonstrated an increase in intestinal tumor multiplicity and tumor progression. Increases in intussusceptions and desmoid lesions were also observed. We have shown that CEACAM1-L associates with beta-catenin by co-immunoprecipitation and colocalization in CEACAM1-L-transfected CT26 and CT51 mouse colon carcinoma cells. Ceacam1(-/-) enterocytes displayed decreased glycogen synthase kinase 3-beta activity with corresponding nuclear localization of beta-catenin. Increased T-cell factor/Lef transcriptional activity was observed in CEACAM1-null CT51 colonic cells and in Caco2 colon cancer cells in which CEACAM1 was downregulated. A significant increased expression in c-Myc and cyclin D1 targets of the Wnt signaling pathway was also revealed in the Ceacam1(-/-) intestine. CEACAM1 therefore actively participates in Wnt signaling in intestinal cells and its downregulation in intestinal tissue contributes to malignancy by augmenting tumor multiplicity and progression.


Comparative evaluation of the GP5+/6+, MY09/11 and PGMY09/11 primer sets for HPV detection by PCR in oral squamous cell carcinomas.
The aim of this study was to evaluate the use of GP5+/6+, MY09/11 and PGMY09/11 primer sets for the detection of human papillomavirus (HPV) DNA by single step polymerase chain reaction (PCR) and nested PCR in formalin-fixed and paraffin-embedded (FFPE) tissues from oral squamous cell carcinomas (OSCCs). DNA extracted from FFPE tissues were tested for amplification of the human beta globin gene with PCO3/4 primers. Positive samples for this gene were tested for HPV DNA using single step PCR with GP5+/6+, MY09/11 and PGMY09/11 primer sets. All negative samples at single step PCR with MY09/11 and PGMY09/11 were subjected to a further PCR with GP5+/6+ primers using the non-amplified product in the previously reactions (nested PCR) as samples. Among 26 samples, 23 were positive for the human beta globin gene and were considered viable for HPV DNA detection by PCR. Single step PCR with GP5+/6+ and MY09/11 primers and MY/GP+ nested PCR did not amplify HPV DNA in any samples. PGMY09/11 primers detected HPV DNA in 13.0% of OSCC cases and this rate was raise to 17.4% with the use of PGMY/GP+ nested PCR. According to our results the PGMY/GP+ nested PCR is the most appropriate primer set for the detection of HPV DNA using FFPE samples from OSCC.


Regulation of p70S6k, GSK-3beta, and calcineurin in rat striated muscle during aging.
In this study we compared the content and phosphorylation levels of several molecules believed to regulate muscle hypertrophy and fiber type changes in the extensor digitorum longus (EDL), soleus, diaphragm, and heart of adult (6 months), aged (30 months), and very aged (36 months) Fischer 344 x Brown Norway rats. With aging, the mass of the EDL and soleus decreased significantly (approximately 38% and approximately 36%, respectively), the diaphragm's mass remained unchanged while the mass of the heart increased (approximately 35%). Western blotting demonstrated that calcineurin (CnA), the 70-kDa ribosomal S6 kinase (p70(S6k)), glycogen synthase kinase-3beta (GSK-3beta), and the phosphorylated forms of GSK-3beta and p70(S6k) (p-GSK-3beta(Ser9) and p-p70(S6kThr389)) were regulated differently with aging and between muscle types. Total p70(S6k), GSK-3beta, and p-GSK-3beta(Ser9) decreased in the aged-atrophic EDL and soleus while p-p70(S6kThr389) increased. Although total p70(S6k) content diminished in the continuously active diaphragm, phosphorylation of p70(S6k )remained unchanged. Conversely, the expression of GSK-3beta and p-GSK-3beta(Ser9) increased in the diaphragm. With aging, the amount of p-p70(S6kThr389) decreased approximately 56% in the heart while p-GSK-3beta( Ser9) increased approximately 193%. Interestingly, CnA content remained unchanged in the diaphragm, increased approximately 204% in the EDL, and decreased approximately 30% and approximately 65% with aging in the soleus and heart, respectively. These results indicate remarkable differences in the regulation of molecules thought to govern protein synthesis and changes in contractile protein expression.


Fractionation of lignin using organic solvents: A combined experimental and theoretical study.
Refining of industrial lignin to produce homogeneous fractions is essential for high-value applications. However, the understanding of key interactions between a variety of solvents with lignin polymer is still uncertain. In this work, single-step fractionation of industrial hardwood kraft lignin (HKL) using organic solvents of different polarities - ethanol, acetone, diethyl ether and hexane - was investigated by combining an experimental and theoretical approach. Experimental results revealed that higher polarity solvents (ethanol and acetone) exhibited higher solubility yield compared to moderate and low polarity solvents. The chemical differences between lignin fractions were proven by pyrolysis gas chromatography mass spectrometry and near infrared spectroscopy. Density functional theory (DFT) results indicated that ethanol presented higher interaction energy followed by acetone, diethyl ether and hexane, which was consistent with experimental findings. Hydrogen bond and non-covalent interaction results from DFT demonstrated that the predominant interaction was found for high polarity of ethanol over other solvents and γ-OH in the lignin model is the key site.