Glutaredoxin like protein (RtGRL1) regulates H2O2 and Na+ accumulation by maintaining the glutathione pool during abiotic stress.
Reaumuria trigyna, an endangered recretohalophyte, is a small archaic wild shrub endemic to arid and semiarid plateau regions of Inner Mongolia, China. Based on salt-related transcriptomic data, we isolated a GRX family gene, glutaredoxin like protein (RtGRL1), from R. trigyna that is associated with the removal of active oxygen and regulation of redox status. RtGRL1 encodes a plasma membrane and chloroplast-localized protein induced by salt, cold, drought stress, ABA, and H2O2. In Arabidopsis thaliana, ectopically expressed RtGRL1 positively regulated biomass accumulation, chlorophyll content, germination rate, and primary root length under salt and drought stress. Overexpression of RtGRL1 induced expression of genes related to antioxidant enzymes and proline biosynthesis, thus increasing glutathione biosynthesis, glutathione-dependent detoxification of reactive oxygen species (ROS), and proline content under stress. Changes in RtGRL1 expression consistently affected glutathione/oxidizedglutathione and ascorbate/dehydroascorbate ratios and H2O2 concentrations. Furthermore, RtGRL1 promoted several GSH biosynthesis gene transcripts, decreased leaf Na+ content, and maintained lower Na+/K+ ratios in transgenic A. thaliana compared to wild type plants. These results suggest a critical link between RtGRL1 and ROS modulation, and contribute to a better understanding of the mechanisms governing plant responses to drought and salt stress.


The study of immune checkpoint inhibitors in chronic hepatitis B virus infection.
Chronic hepatitis B (CHB) is a contagious disease caused by the hepatitis B virus, which can damage the liver via cirrhosis or cancer. Existing CHB treatments are not completely effective; immune checkpoint inhibitors show potential hope for treating CHB, but their safety and efficacy need to be further validated. In this review, we introduce the mechanisms of CHB virus infection, the expression of immune checkpoints during CHB, and the treatments that are currently available. Finally, we discuss the possibilities for using immune checkpoint inhibitors to treat CHB.


Ontogeny and induction of hepatic isometallothioneins in immature rats.
It is well established that hepatic concentrations of metallothioneins (MTs) are very high in developing rats. In this study, the ontogeny of hepatic isometallothioneins (MT-I and MT-II) was determined. MTs were separated and quantitated with a high-performance liquid chromatography (HPLC) method. MT-I and MT-II, first detected in fetal liver on gestation Day 18, increased coordinately during late gestation and reached maximum hepatic concentrations of approximately 400 and 500 micrograms/g, respectively, which were maintained from postpartum Days 1 through 7. Thereafter, MT concentrations decreased, reaching concentrations similar to adult levels (approximately 10 micrograms/g liver) between 28 and 35 days of age. MT-II was significantly higher than MT-I in 14- and 21-day-old rats. In 35-day-old rats, MT-I was below the detection limit. MT-I and MT-II mRNA levels were quantitated by Northern blot hybridization with mouse cRNA probes. In contrast to protein concentrations, MT mRNA reached maximal levels during late gestation which were maintained throughout the first 3 weeks postpartum. Additional experiments indicated that Cd (1-30 mumol/kg), Zn (100-3000 mumol/kg), and dexamethasone (0.3-10 mumol/kg) increased hepatic concentrations of MT-I and MT-II and their respective mRNAs in 14-day-old rats, despite the preexisting high levels of protein and mRNA at this time. These results indicate that hepatic concentrations of MT-I and MT-II isoproteins and mRNA, which increase coordinately during fetal development, decline differently during neonatal development. In 14-day-old neonates, MT-I and MT-II genes are responsive to Cd, Zn, and dexamethasone when constitutive levels of both MT mRNA and isoproteins are high.


Ultrastructure of Hanseniaspora ascospores.
A comparative study of the ultrastructure in sections of the ascospores of six Hanseniaspora species showed three types of spores: (1) hat-shaped in H. valbyensis and H. guilliermondii, (2) spherical with an equatorial or subequatorial ledge, smooth or rough in H. occidentalis and H. uvarum, (3) spherical with warts in H. osmophila and H. vineae. Development and germination of the spores of Hanseniaspora guilliermondii is described in more detail.


Mitogen-activated protein kinases (p38 and c-Jun NH2-terminal kinase) are differentially regulated during cardiac volume and pressure overload hypertrophy.
Chronic pressure overload (PO) and volume overload (VO) result in morphologically and functionally distinct forms of myocardial hypertrophy. However, the molecular mechanism initiating these two types of hypertrophy is not yet understood. Data obtained from different cell types have indicated that the mitogen-activated protein kinases (MAPKs) comprising c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 play an important role in transmitting signals of stress stimuli to elicit the cellular response. We tested the hypothesis that early induction of MAPKs differs in two types of overload on the heart and associates with distinct expression of hypertrophic marker genes, namely ANF, alpha-myosin heavy chain (alpha-MHC), and beta-MHC. In rats, VO was induced by aortocaval shunt and PO by constriction of the abdominal aorta. The PO animals were further divided into two groups depending on the severity of the constriction, mild (MPO) and severe pressure overload (SPO), having 35 and 85% aortic constriction, respectively. Early changes in MAPK activity (2-120 min and 1 to 2 d) were analyzed by the in vitro kinase assay using kinase-specific antibodies for p38, JNK, and ERK2. The change in expression of hypertrophy marker genes was examined by Northern blot analysis. In VO hypertrophy, the activity of p38 was markedly increased (10-fold), without changing the activity of ERK and JNK. However, during PO hypertrophy, the activity of JNK was significantly increased (two- to sixfold) and depended on the severity of the load. The activity of p38 was not changed in MPO hypertrophy, whereas it was slightly elevated (50%) in hearts with SPO. Similarly, ERK activity was not changed in hearts with MPO, but a transient rise in activity was observed in hearts with SPO. The expression of ANF and beta-MHC genes was elevated in both PO and VO hypertrophy; however, this change was much greater in hearts subjected to PO than VO hypertrophy. Alpha-MHC expression was downregulated in PO but remained unchanged in VO hypertrophy hearts. Thus, these results demonstrate differential activation of MAPKs in two types of cardiac hypertrophy and this, in part, may contribute to differential expression of cardiac muscle gene expression, giving rise to unique cardiac phenotype associated with different hemodynamic overloads.


miR-181b/Oncostatin m axis inhibits prostate cancer bone metastasis via modulating osteoclast differentiation.
The activation of osteoblasts is significantly correlated to prostate tumor bone metastasis and bone loss. Oncostatin M (OSM) could promote breast cancer metastasis to bone. However, its role and mechanism in prostate cancer bone metastasis remain unclear. MicroRNAs (miRNAs) could play important roles in cancers via post-transcriptionally regulating target genes via binding to specific sequences in the 3' UTR of downstream target genes. In the present study, we performed microarray profiling analyses to identify differentially-expressed miRNAs in preosteoclast before and after osteoclast differentiation that could target OSM. miR-181b-5p was downregulated during Raw264.7 cells differentiation into osteoclast. By direct targeting OSM 3' UTR, miR-181b-5p inhibited OSM messenger RNA expression and protein levels, subsequently decreasing IL-6 and AREG and increasing OPG, while OSM overexpression exerted an opposing effect. More importantly, co-culture with miR-181b-5p-overexpressing differentiated Raw264.7 cells suppressed proliferation, migration, and invasion of mouse prostate cancer RM-1 cells, while co-culture with OSM-overexpressing Raw264.7 cells led to opposing cellular effects. More importantly, the effects of miR-181b-5p on osteoclastogenic factors and RM-1 cells could be significantly reversed by OSM overexpression. In summary, miR-181b-5p/OSM axis could be a viable therapeutic target for patients with surgically removed primary tumors to reduce bone metastasis and prevent bone loss.


Semi-quantitative myocardial perfusion measured by computed tomography in patients with refractory angina: a head-to-head comparison with quantitative rubidium-82 positron emission tomography as reference.
Computed tomography (CT) is a novel method for assessment of myocardial perfusion and has not yet been compared to rubidium-82 positron emission tomography (PET). We aimed to compare CT measured semi-quantitative myocardial perfusion with absolute quantified myocardial perfusion using PET and to detect stenotic territories in patients with severe coronary artery disease. Eighteen patients with stenosis narrowing coronary arteries ≥70% demonstrated on invasive coronary angiography underwent rest and adenosine stress imaging obtained by 320-multidetector CT scanner and CT/PET 64-slice scanner. CT measured myocardial attenuation density (AD) and perfusion index (PI) were correlated to absolute PET myocardial perfusion values. Rest AD, rest and stress PI did not correlate to PET findings (r = 0·412, P = 0·113; r = 0·300, P = 0·259; and r = 0·508, P = 0·064, respectively). However, there was a significant correlation between stress AD and stress PET values (r = 0·670, P = 0·009) and between stress and rest differences for AD and PI with PET differences (r = 0·620, P = 0·006; and r = 0·639, P = 0·004, respectively). Furthermore, significant differences were observed between remote and stenotic territories for rest and stress AD (48 ± 14HU and 37 ± 16HU, P = 0·002; 76 ± 19HU and 58 ± 13HU, P<0·001, respectively), PI (9·6 ± 2·9 and 7·5 ± 3·1, P = 0·002; 21·6 ± 4·1 and 16·9 ± 3·9, P<0·001, respectively) and PET (0·96 ± 0·37 ml g-1 min-1 and 0·86 ± 0·26 ml g-1 min-1 , P = 0·036; 2·07 ± 0·76 ml g-1 min-1 and 1·61 ± 0·76 ml g-1 min-1 , P = 0·006, respectively). Semi-quantitative CT parameters may be useful in the detection of myocardium subtended by stenotic coronary arteries.


Inhibition of prostacyclin synthesis in endothelial cells by methylisobutylxanthine is not mediated through elevated cAMP level.
Methylisobutylxanthine (MIX) raised cAMP levels and inhibited prostacyclin synthesis and arachidonic acid release in endothelial cells from both pig aorta and human umbilical vein. These effects were reversible and dose dependent on MIX concentrations. Dibutyryl cAMP (3 mM) alone did not inhibit prostacyclin synthesis or arachidonic acid release. When added with MIX, dibutyryl cAMP did not enhance the inhibition elicited by MIX. MIX inhibited the formation of lysophospholipids, 1,2-diacylglycerol and phosphatidic acid in bradykinin-stimulated pig endothelial cells, suggesting that the inhibition of prostacyclin synthesis resulted from an apparent inhibition of both phospholipase A2 and phospholipase C. Other phosphodiesterase inhibitors, theophylline and mopidamole, also raised cAMP levels and inhibited arachidonic acid release. However, there was no correlation between cAMP levels and these inhibitions. Forskolin, an adenylate cyclase activator, elevated intracellular cAMP levels with no apparent inhibition on prostacyclin synthesis. We conclude that the inhibitory effect of MIX on phospholipase A2 and phospholipase C is probably through mechanisms other than the elevation of the cAMP level.


Comparison of prevalence, resistance, biofilm-forming ability and virulence between carbapenem-non-susceptible and carbepenem-susceptible Enterobacter cloacae complex in clusters.
This study aimed to explore differences in prevalence, resistance, biofilm-forming ability and virulence between carbapenem-non-susceptible and carbapenem-susceptible Enterobacter cloacae complex (ECC) in different clusters. Ninety-one carbapenem-non-susceptible isolates and an equal number of carbapenem-susceptible isolates and their clinical information were collected from a university teaching hospital in China. The strains were divided into different clusters based on hsp60 analysis. The agar dilution method was used to determine the minimum inhibitory concentrations of common antibiotics. The crystal violet assay was used to measure biofilm-forming ability. The Galleria mellonella infection model and polymerase chain reaction of virulence genes were used to evaluate virulence. The isolates were divided into 12 clusters based on hsp60 analysis. Cluster VIII accounted for a greater proportion of carbapenem-non-susceptible isolates than the other clusters. The same clusters exhibited different resistance rates in carbapenem-non-susceptible and carbapenem-susceptible isolates. Moreover, carbapenem-non-susceptible isolates carried fewer virulence genes than carbapenem-susceptible isolates, and carbapenem-non-susceptible isolates in cluster II in did not carry the detected virulence genes. Virulence of carbapenem-non-susceptible and carbapenem-susceptible isolates differed significantly in clusters I, III, VIII and IX, as evaluated using the G. mellonella infection model. Carbapenem-non-susceptible isolates in cluster VIII showed higher prevalence, resistance, biofilm-forming ability and pathogenicity compared with the other clusters. The study findings indicate the need to identify subgroups of ECC, and provide better advice and guidance for the use of carbapenems.


The microbiome modulates arbovirus transmission in mosquitoes.
Mosquito-transmitted arthropod-borne viruses (arboviruses) such as dengue virus, chikungunya virus, and West Nile virus constitute a major public health burden and are increasing in severity and frequency worldwide. The microbiota associated with mosquitoes (comprised of viruses, bacteria, fungi and protozoa) can profoundly influence many host phenotypes including vector competence, which can either be enhanced or suppressed. Thus, the tripartite interactions between the mosquito vector, its microbiota and the pathogens they transmit offer novel possibilities to control arthropod-borne diseases.


Prevalence of hepatitis A antibodies in French recruits in 1985.
The epidemiological study of hepatitis A antibodies prevalence in 1000 french recruits shows a 20% fall in people of 18-20 years old between 1979 and 1985, and identifies variables such as residence in coasting area, stay overseas, study level, as the most important social and geographical risk factors. These results are in agreement with the evolution observed in different other european countries.


Characterization of the glutamate dehydrogenase gene and its regulation in a euryhaline copepod.
Glutamate dehydrogenase (GDH) plays a key role in the metabolism of free amino acids (FAA) in crustaceans and other metazoans. Glutamate synthesized by GDH via reductive amination is the amino group donor for alanine synthesis and the precursor required for proline synthesis. Since both proline and alanine are important intracellular osmolytes in many marine invertebrates, GDH has been widely implicated as playing a central role in response to hyperosmotic stress in these organisms. We have isolated the gene encoding a GDH homolog from the euryhaline copepod Tigriopus californicus and examined the regulation of GDH under salinity stress. The gene encodes a protein of 557 residues with 76% amino acid identity with Drosophila melanogaster GDH. The gene encodes an N-terminal mitochondrial signal sequence peptide. Only a single intron of 71 bp was found in the GDH gene in T. californicus when genomic sequences and cDNA sequences were compared. The levels of GDH mRNA do not increase during hyperosmotic stress in this copepod. The effects of salt and hyperosmotic stress on GDH enzyme activity were also investigated. GDH activities decrease with increasing NaCl concentrations in in vitro enzyme assays, while live animals exposed to hyperosmotic stress showed no change in GDH enzyme activities. Combined, these results indicate that GDH transcription and enzyme activity do not appear to function in the regulation of alanine and proline accumulation during hyperosmotic stress in T. californicus. The manner in which this important physiological process is regulated remains unknown.


Phylogenetic analysis of IDD gene family and characterization of its expression in response to flower induction in Malus.
Although INDETERMINATE DOMAIN (IDD) genes encoding specific plant transcription factors have important roles in plant growth and development, little is known about apple IDD (MdIDD) genes and their potential functions in the flower induction. In this study, we identified 20 putative IDD genes in apple and named them according to their chromosomal locations. All identified MdIDD genes shared a conserved IDD domain. A phylogenetic analysis separated MdIDDs and other plant IDD genes into four groups. Bioinformatic analysis of chemical characteristics, gene structure, and prediction of protein-protein interactions demonstrated the functional and structural diversity of MdIDD genes. To further uncover their potential functions, we performed analysis of tandem, synteny, and gene duplications, which indicated several paired homologs of IDD genes between apple and Arabidopsis. Additionally, genome duplications also promoted the expansion and evolution of the MdIDD genes. Quantitative real-time PCR revealed that all the MdIDD genes showed distinct expression levels in five different tissues (stems, leaves, buds, flowers, and fruits). Furthermore, the expression levels of candidate MdIDD genes were also investigated in response to various circumstances, including GA treatment (decreased the flowering rate), sugar treatment (increased the flowering rate), alternate-bearing conditions, and two varieties with different-flowering intensities. Parts of them were affected by exogenous treatments and showed different expression patterns. Additionally, changes in response to alternate-bearing and different-flowering varieties of apple trees indicated that they were also responsive to flower induction. Taken together, our comprehensive analysis provided valuable information for further analysis of IDD genes aiming at flower induction.


A clinical study of cervical dysplasia in long-term survivors of allogeneic stem cell transplantation.
This retrospective study examined the prevalence of and risk factors for cervical dysplasia and genital human papillomavirus (HPV) infection in 89 female recipients of allogeneic stem cell transplantation (allo-SCT) between 1985 and 2005 who survived for more than 5 years after transplantation. All patients underwent regular gynecologic examination and cervical cytological testing. The incidence rates of cervical cytological abnormalities and HPV infection were calculated. Various clinical parameters were evaluated for association with cytological high-grade squamous intraepithelial lesion (HSIL) posttransplantation to identify risk factors for cervical dysplasia. Multivariate analysis with logistic regression was used to identify independent risk factors for cervical dysplasia after adjusting for confounding factors. Sixty-one of the 89 patients (68.5%) had cervical cytological abnormalities of varying grades, including atypical squamous cells of undetermined significance (ASC-US; 31.5%; 28 of 89), low-grade squamous intraepithelial lesion (LSIL; 10.1%; 9 of 89), and HSIL (27%; 24 of 89). HPV status was available for 43 patients, 12 of whom (27.9%) were HPV-positive. Among the 69 patients with normal cytological cervical smear findings pretransplantation, the incidence of cytological HSIL was 23.2% (16 of 69) posttransplantation. After adjusting for confounding factors, only unrelated HLA-matched donor and the presence of vulvovaginal chronic graft-versus-host disease (cGVHD) were independent risk factors for cervical cytology HSIL after transplantation, with the highest risk among patients with vulvovaginal cGVHD (adjusted odds ratio, 31.97). We conclude that long-term survivors of allogeneic stem cell transplantation are at high risk for cervical cytological abnormalities. Vulvovaginal cGVHD and unrelated HLA-matched donor were the only independent risk factors for cervical cytological HSIL in patients with normal cervical cytology before transplantation. Regular surveillance by gynecologic examination, including cervical cytological testing, in these patients allows for early diagnosis and effective management of cervical abnormality and decreases the burden of this potentially fatal, but treatable, condition.


Preparation, characterization, cellular response and in vivo osseointegration of polyetheretherketone/nano-hydroxyapatite/carbon fiber ternary biocomposite.
As FDA-approved implantable material, polyetheretherketone (PEEK) is becoming a prime candidate to replace traditional surgical metallic implants made of titanium (Ti) and its alloys, since it has a lower elastic modulus than Ti. The bioinertness and defective osteointegration of PEEK, however, limit its clinical adoption as load-bearing dental/orthopedic material. The present work aimed at developing a PEEK bioactive ternary composite, polyetheretherketone/nano-hydroxyapatite/carbon fiber (PEEK/n-HA/CF), and evaluating it as a potential bone-repairing material by assessment of growth and differentiation of osteoblast-like MG63 cells and by estimation of osteointegration in vivo. Our results indicated that the adhesion, proliferation and osteogenic differentiation of cells, as well as the mechanical properties were greatly promoted for the PEEK/n-HA/CF biocomposite compared with pure PEEK matrix. More importantly, the ternary composite implant boosted in vivo bioactivity and osseointegration in canine tooth defect model. Thus, the PEEK/n-HA/CF ternary biocomposite with enhanced mechanics and biological performances hold great potential as bioactive implant material in dental and orthopedic applications.


[Role of antral gastrin in regulating gastric secretion and bile flow].
In chronic experiments on dogs with removed mucosa of the antral portion of the stomach, administration of the liver extract into the stomach or intestine decreased the output of hydrochloric acid as compared with intract animals. The liver extract administration caused no raise of gastrin level in the blood serum of the operated animals.


Morphometric measurements and sexual dimorphism of the piriform aperture in adults.
The aim of this study was to evaluate the dimensions (maximal width and length), the size and the shape of the PA and their sexual dimorphism. Using 3D-CT scan reconstructions and landmarks positioning around the piriform aperture and on the face, a collective of 170 non-pathologic subjects (79 female, 91 male) from Marseille (France) was examined in classical and geometric morphometrics methods. The mean width of the piriform aperture was 24.00 mm in females and 25.32 mm in males, the mean length was 32.54 mm in females and 36.35 mm in males. The difference between males and females was significant, and our data correlates well with the previously data acquired from humans skulls. Facial measurements also showed a statistically significant dimorphism. In morphometric geometrics, the correlation between the centroïd size and PC1 in the shape space was weak, while this correlation was strong in the size and shape space. Visualization of shape differences was achieved on 2D wireframes. Shape and size analysis of the piriform aperture showed the existence of a significant sexual dimorphism. These results encourage us to go further with functional and imaging correlations.


Prolonged and unprolonged complex febrile seizures differently affect frontal theta brain activity.
Studies have identified mild but persistent cognitive and functional deficits, which could be linked to each other, in children with complex febrile seizures (FS). Our aim was to investigate differences in brain activity in children with a history of complex FS, through a study paradigm notably associated with the development of learning capacities and using electroencephalographic (EEG) signal. To further increase our understanding of these differences, complex FS were studied separately depending on their type. EEG was recorded in 43 children with past FS. Brain activity associated with auditory learning was investigated using a habituation paradigm, in which repetition suppression (RS) is typically found following stimulus repetition. Auditory stimuli were repeated three times, and each presentation were analysed separately in the time-frequency (TF) domain. A mixed-analysis of variance was used to assess differences in spectral power between stimulus repetition and FS type (simple vs complex prolonged; CP vs complex unprolonged; CUP). Repetition effects were found in the 3-6 Hz during 150-600 ms time window after stimulus onset at frontal sites (F(2, 40) = 5.645, p = 0.007, η2p = 0.220). Moreover, an interaction effect between stimulus repetition and FS type (F(4, 80) = 2.607, p = 0.042, η2p = 0.115) was found. Children with CP FS showed greater increase in spectral power in response to the first stimulus presentation, while children with CUP FS failed to show a RS pattern. Our results show distinct abnormalities in brain activity to a habituation paradigm. We argue that these changes suggest children with CP FS may be hyperexcitable, while children with CUP FS show impaired habituation processes. Still, these differences may be associated with other clinical features linked to complex FS as well. Hence, the role of these differences in complex FS incidence and prognosis should be the subject of future studies.


Lymphangiomyomatosis: a report of three cases treated with tamoxifen.
Three cases are reported of lymphangiomyomatosis with pulmonary and abdominal manifestations. Two had a chylous pleura effusion, while the third presented a retroperitoneal manifestation, which was completely resectable. Antiestrogen therapy with tamoxifen was administered in all three cases. Two patients died of pulmonary progression after 4 months of therapy. The third is still alive, with stable disease for more than 6 years, and has been receiving tamoxifen for 66 months. These observations indicate that antiestrogen treatment may be as effective as oophorectomy when started at an early stage of the disease.


Small coronary calcium deposits and elevated plasma levels of oxidized low density lipoprotein are characteristic of acute myocardial infarction.
Predictions of the onset of acute myocardial infarction (AMI) in high risk individuals are of great clinical importance. Among various risk factors, elevated levels of oxidized low density lipoprotein (ox-LDL) in plasma have been shown to reflect unstable coronary plaques. Coronary calcification is a common finding in the elderly, however, its clinical implications as a risk factor for plaque rupture are controversial. This study was designed to investigate the clinical implications of plasma ox-LDL levels and coronary calcification detected by electron-beam computed tomography (EBCT), by comparing patients with AMI with those with stable angina pectoris (SAP). We measured plasma ox-LDL levels in AMI (n=34) and SAP (n=49) patients. In addition, a coronary calcium score was quantified with the Agatston system. The total coronary calcium score (TCS) was defined as the sum of the scores for each lesion. TCS and total calcium area were significantly smaller in patients with AMI than in those with SAP. On the other hand, plasma ox-LDL levels were significantly higher in AMI patients than in SAP patients (p<0.0005). These results suggest that a combined assessment of coronary calcium and plasma ox-LDL levels may be useful for screening patients with unstable coronary plaques.


Two-way interdomain signal transduction in tetracycline repressor.
The transcription of genes encoding resistance to the antibiotic, tetracycline (Tc), is repressed by tetracycline repressor (TetR), which is a homodimeric alpha-helical protein possessing a small N-terminal DNA binding domain (DNB domain) and a larger C-terminal domain (TBD domain). Binding of Tc to the TBD domain induces a subtle conformational change in the DNB domain that leads to abrogation of its DNA-binding activity, and induction of Tc resistance. While most previous studies on TetR have focused on the effects of Tc-binding on the DNB domain conformation, here we have investigated the role of the DNB domain in modulating Tc binding. We have discovered that a TBD domain construct entirely lacking the DNB domain displays a drastic reduction in Tc-binding affinity even though the DNB domain is far from the Tc-binding site. In the context of full-length TetR, highly destabilizing amino acid substitutions in the DNB domain cause reductions in Tc-binding activity. Strikingly, the DNB domains of these mutants, which are completely unfolded in the absence of Tc, are induced to fold when Tc is bound. These results demonstrate that there is a previously unrecognized two-way interdomain signaling mechanism in TetR whereby the DNB domain is required for maximal Tc-binding by the TBD domain, and Tc-binding in the TBD domain leads to stabilization of the DNB domain. Furthermore, our work suggests that detailed thermodynamic and kinetic studies on mutant forms of other allosteric proteins may also reveal surprising and previously undetected modes of interdomain communication.


Intravenous morphine at 0.1 mg/kg is not effective for controlling severe acute pain in the majority of patients.
The objective was to quantify the analgesic effect of a dose of intravenous morphine, 0.1 mg/kg, to emergency department (ED) patients presenting in acute, severe pain. This was a prospective convenience cohort of patients aged 21 to 65 years and presenting to an academic urban ED with acute, severe pain. Patients rated their pain intensity on a validated 11-point verbal numeric rating scale ranging from 0, "no pain," to 10, "worst possible pain," immediately before they received 0.1 mg of intravenous morphine per kilogram of body weight and 30 minutes later. The main outcome was proportion of patients whose pain decreased by less than 50% during the 30-minute interval. Of 119 patients who received intravenous morphine at 0.1 mg/kg, the average age was 42 years (SD=11 years), 55% were female patients, 65% were Hispanic, 28% were black, and 7% were classified as other. The median numeric rating scale pain score at baseline was 10 (interquartile range 9 to 10). Sixty-seven percent (95% confidence interval 58% to 76%) of the patients receiving intravenous morphine at 0.1 mg/kg reported a less than 50% decrease in pain. No patient required an opioid antagonist at any time during or after the study period. The data suggest that a 0.1 mg/kg dose of morphine may be too low to adequately control acute severe pain.


Chiropractic adjustment to the cervical spine and the Arnold-Chiari malformation.
To present two cases in which patients with Type I Arnold-Chiari malformation (ACM) were treated with adjustments to the cervical spine for conditions unrelated to the anomaly. The ACM is an anomaly of central nervous system development in which structures from the posterior fossa descend below the level of the foramen magnum. The patients reported were adjusted multiple times to the cervical spine. No ill effects or complications were noted related to the ACM. Asymptomatic Type I ACM is not necessarily a contraindication to skilled adjustments to the cervical spine.


[Quality assurance--quo vadis? What expectations does science have? From quality assurance to health services research].
Surgical quality control may be developed in applied research. Using methods of clinical epidemiology, the efficacy of therapeutic and diagnostic procedures may be tested in wide fields of patient care. Thereby deficits may be unvealed very rapidly. Applied research pointing towards patient care has to be interdisciplinary and multicentric. A specific role has to be taken by the local boards of medicine.


Expression of neuronal nicotinic acetylcholine receptor subunit mRNAs within midbrain dopamine neurons.
Many behavioral effects of nicotine result from activation of nigrostriatal and mesolimbic dopaminergic systems. Nicotine regulates dopamine release not only by stimulation of nicotinic acetylcholine receptors (nAChRs) on dopamine cell bodies within the substantia nigra and ventral tegmental area (SN/VTA), but also on presynaptic nAChRs located on striatal terminals. The nAChR subtype(s) present on both cell bodies and terminals is still a matter of controversy. The purpose of this study was to use double-labeling in situ hybridization to identify nAChR subunit mRNAs expressed within dopamine neurons of the SN/VTA, by using a digoxigenin-labeled riboprobe for tyrosine hydroxylase as the dopamine cell marker and (35)S-labeled riboprobes for nAChR subunits. The results reveal a heterogeneous population of nAChR subunit mRNAs within midbrain dopamine neurons. Within the SN, almost all dopamine neurons express alpha2, alpha4, alpha5, alpha6, beta2, and beta3 nAChR mRNAs, with more than half also expressing alpha3 and alpha7 mRNAs. In contrast, less than 10% express beta4 mRNA. Within the VTA, a similar pattern of nAChR subunit mRNA expression is observed except that most subunits are expressed in a slightly lower percentage of dopamine neurons than in the SN. Within the SN, alpha4, beta2, alpha7, and beta4 mRNAs are also expressed in a significant number of nondopaminergic neurons, whereas within the VTA this only occurs for beta4. The heterogeneity in the expression of nAChR subunits within the SN/VTA may indicate the formation of a variety of different nAChR subtypes on cell bodies and terminals of the nigrostriatal and mesolimbic pathways.


Ataxia-Pancytopenia Syndrome Is Caused by Missense Mutations in SAMD9L.
Ataxia-pancytopenia (AP) syndrome is characterized by cerebellar ataxia, variable hematologic cytopenias, and predisposition to marrow failure and myeloid leukemia, sometimes associated with monosomy 7. Here, in the four-generation family UW-AP, linkage analysis revealed four regions that provided the maximal LOD scores possible, one of which was in a commonly microdeleted chromosome 7q region. Exome sequencing identified a missense mutation (c.2640C>A, p.His880Gln) in the sterile alpha motif domain containing 9-like gene (SAMD9L) that completely cosegregated with disease. By targeted sequencing of SAMD9L, we subsequently identified a different missense mutation (c.3587G>C, p.Cys1196Ser) in affected members of the first described family with AP syndrome, Li-AP. Neither variant is reported in the public databases, both affect highly conserved amino acid residues, and both are predicted to be damaging. With time in culture, lymphoblastic cell lines (LCLs) from two affected individuals in family UW-AP exhibited copy-neutral loss of heterozygosity for large portions of the long arm of chromosome 7, resulting in retention of only the wild-type SAMD9L allele. Newly established LCLs from both individuals demonstrated the same phenomenon. In addition, targeted capture and sequencing of SAMD9L in uncultured blood DNA from both individuals showed bias toward the wild-type allele. These observations indicate in vivo hematopoietic mosaicism. The hematopoietic cytopenias that characterize AP syndrome and the selective advantage for clones that have lost the mutant allele support the postulated role of SAMD9L in the regulation of cell proliferation. Furthermore, we show that AP syndrome is distinct from the dyskeratoses congenita telomeropathies, with which it shares some clinical characteristics.


DC-SIGN signalling induced by Trichinella spiralis products contributes to the tolerogenic signatures of human dendritic cells.
Tolerogenic dendritic cells (tolDCs) are central players in the maintenance of immune tolerance and thereby have been identified as the most favourable candidates for cell therapy of autoimmune diseases. We have recently shown that excretory-secretory products (ES L1) released by Trichinella spiralis larvae induce stable human tolDCs in vitro via Toll-like receptor 2 (TLR2) and TLR4. However, engagement of these receptors did not fully explain the tolerogenic profile of DCs. Here, we observed for the first time that dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) interacts with highly glycosylated ES L1 and contributes to the generation of ES L1-induced tolDCs. Blocking DC-SIGN interfered with the ES L1-induced higher expression of CD40 and CCR7 and the production of IL-10 and TGF-β by DCs. The cooperation of TLR2, TLR4 and DC-SIGN receptors is of importance for the capacity of DCs to prime T cell response toward Th2 and to induce expansion of CD4+CD25+Foxp3+ T cells, as well as for the production of IL-10 and TGF-β by these cells. Overall, these results indicate that induction of tolDCs by ES L1 involves engagement of multiple pattern recognition receptors namely, TLR2, TLR4 and DC-SIGN.


Qualitative and quantitative evaluation of EHR-integrated mobile patient questionnaires regarding usability and cost-efficiency.
The objective of this evaluation study is to assess a web-based application, currently available on iPad, to document questionnaires regarding patient reported outcomes such as quality of life. Based on the single source approach, the results of these questionnaires are available in the electronic health record to be used for treatment and research purposes. The assessment focuses on the usability and efficiency of the system. The system usability scale questionnaire with seven additional items was used to rate the usability by the patients. It was formally validated by a Cronbach Alpha test. In addition, semi-structured interviews were conducted with patients and medical staff. Time and cost measures, based on official tables of costs, were taken through workflow observations. This study was conducted in the department of dermatology at the University Hospital of Münster, Germany from April to June 2011. Using the web-based application questionnaire, results about patient reported outcomes like quality of life are immediately available in the electronic health record and can be used for treatment or research purposes. 118 patients and four staff members participated in the study. The usability score reached 80 from 100 points and patients as well as medical staff stated in the interviews that the usability of the web-based system was high, and they preferred it to the previously used paper-based questionnaires. In the setting of our pilot department the mobile devices amortized their costs after 6.7 months. In general, depending on the professional group who are going to post process the paper-based forms, the earliest break-even point to use mobile questionnaires is at 1737 paper sheets per year. The mobile patient questionnaires, integrated into the electronic health record, were well accepted in our pilot setting with high usability scores from patients and medical staff alike. The system has also proved to be cost-efficient compared to the paper-based workflow, given that a certain number of questionnaires is used per year.


The effect of pH-adjusted 2-chloroprocaine on the onset of epidural analgesia in pregnant patients in the lying and sitting position during the first stage of labor.
The purpose of this prospective, randomized, double-blind study was to compare the epidural onset time of 2% 2-chloroprocaine with pH-adjusted 2-chloroprocaine administered in either the sitting or supine position in pregnant patients during the first stage of labor. Patients in Groups I and III received the control solution in the sitting and supine position, respectively. Patients in Groups II and IV received the buffered solution in the sitting and supine position, respectively. The pH and pCO2 of the control and buffered solutions differed significantly. The pH and pCO2 of the control and buffered solutions were 4.38 +/- 0.01, 18.4 +/- 2.2 mm Hg and 7.70 +/- 0.04, 114.9 +/- 3.0 mmHg, respectively. A statistically significant reduction in the time of onset of analgesia in the pH-adjusted groups was noted. Groups I and II had onset times of 4 +/- 1.2 and 4.3 +/- 1.0, whereas Groups II and IV had onset times of 2.6 +/- 0.9 and 2.7 +/- 0.6 min., respectively. There were no intergroup differences in the cephalad spread of analgesia or duration of analgesia. Position had no effect on the onset of analgesia at the S2-3 dermatomes nor on the bilateral cephalad spread of the epidural study solutions. Our results indicate that a pregnant patient may be dosed in the lateral supine position without adversely affecting the caudad or cephalad spread of plain or pH-adjusted 2% 2-chloroprocaine, which is clinically important because the incidence of aortocaval compression is increased in the supine position when compared with the lateral supine position.(ABSTRACT TRUNCATED AT 250 WORDS)


Integrated model for land-use transformation analysis based on multi-layer perception neural network and agent-based model.
The efficacy of land-use changes on aquatic ecosystems has been extensively studied in recent decades. Water resource management needs to understand the relationship between land-use change patterns and water quality, especially in urban areas. Hence, recognizing spatial-temporal changes in land use is required for sustainable development and proper water resource management. This research has developed an integrated model based on agent-based model (ABM) and multi-layer perceptron (MLP) neural network technique to predict the future land-use transformation tested on the North Ahvaz watershed, Iran. Random forest-supervised classification technique was applied to derive the land-use maps using Landsat 1989, 2004, and 2019 images in the Google Earth Engine (GEE) platform. The overall accuracy of classified land-use images was 0.82, 0.81, and 0.84, respectively, with the kappa coefficient of 0.74, 0.72, and 0.78. Land-use change analysis and generating transition potential maps were carried out in land change modeler (LCM) through MLP based on seven driving factors. Then, the land-use map for 2019 (for validation) and 2040 was simulated using the transition potential map and an agent-based approach. The ABM scenario was farmers' and urban landowners' decisions to convert undeveloped and unprotected lands to residential lands. The results showed that residential areas and pasture lands would grow by 67.96 km2 and 64.63 km2, and agricultural and barren lands would degrade about 84.19 km2 and 47.98 km2 during 2019-2040, respectively. Predicting land-use change through the integrated MLP-ABM model may be used to evaluate the effects of land-use change coming out of human decision-making.


A vaccine and diagnostic target for Clostridium bolteae, an autism-associated bacterium.
Constipation and diarrhea are common in autistic patients. Treatment with antibiotics against bacteria appears to partially alleviate autistic-related symptoms. Clostridium bolteae is a bacterium that has been shown to be overabundant in the intestinal tract of autistic children suffering from gastric intestinal ailments, and as such is an organism that could potentially aggravate gastrointestinal symptoms. We set out to investigate the cell-wall polysaccharides of C. bolteae in order to evaluate their structure and immunogenicity. Our explorations revealed that C. bolteae produces a conserved specific capsular polysaccharide comprised of rhamnose and mannose units: [→3)-α-D-Manp-(1→4)-β-d-Rhap-(1→], which is immunogenic in rabbits. These findings are the first description of a C. bolteae immunogen and indicate the prospect of using this polysaccharide as a vaccine to reduce or prevent C. bolteae colonization of the intestinal tract in autistic patients, and as a diagnostic marker for the rapid detection of C. bolteae in a clinical setting.


Hemoperfusion in severe chlorprothixene overdose.
Two to twelve hours after suicidal ingestion of an estimated dose of 10 g chlorprothixene, a 31-year-old female was admitted to the emergency ward of the clinic with cardiorespiratory arrest. After successful resuscitation, the further clinical course was complicated by persistent ventricular extrasystoles and ventricular fibrillation which necessitated repeated defibrillation. Since the patient did not respond satisfactorily to supportive treatment, a combined hemoperfusion/hemodialysis was performed. Under extracorporeal detoxication, elimination of chlorprothixene from plasma was accompanied by substantial improvement of the patient's clinical condition, although only about 1.6% of the estimated dose had been removed. This case seems to indicate that evaluation of the therapeutic efficacy of hemoperfusion should not be based exclusively on the relation of the amount of the eliminated drug to total absorbed dose.


Kinetic study of empty fruit bunch using hot liquid water and dilute acid.
Empty fruit bunch (EFB), a residual product of the palm plantation, is an attractive biomass for biorefinery. As xylan is susceptible to high temperature pretreatment, it is important to setup a proper pretreatment condition to maximize the sugar recovery from EFB. Kinetic parameters of mathematical models were obtained in order to predict the concentration of xylose, glucose, furfural, and acetic acid in the hydrolysate and to find production conditions of xylose. We investigated the kinetics of hot liquid water and dilute sulfuric acid hydrolysis over a 40-min period using a self-designed setup by measuring the concentrations of released sugars (xylose, glucose) and degradation products (acetic acid and furfural). The reaction was performed within the range 160∼180 °C, under reaction conditions of various concentration of sulfuric acid (0.1∼0.2%) and 1:7 solid-liquid ratio in a batch reactor. The kinetic constants can be expressed by the Arrhenius equation with the activation energy for the hydrolysis of sugar and decomposition of sugar. The activation energy of xylose was determined to be 136.2187 kJ mol(-1).


Rhizoma Paridis total saponins alleviate H2O2‑induced oxidative stress injury by upregulating the Nrf2 pathway.
Rhizoma Paridis total saponins (RPTS) is an active substance isolated from the traditional Chinese medicine Rhizoma Paridis, which possesses multiple biological activities. The aim of the present study was to explore the roles and mechanisms of RPTS in oxidative stress injury of ARPE‑19 human retinal pigment epithelial cells. Cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP) and apoptosis were determined by Cell Counting kit‑8 assay and flow cytometry, respectively. Enzyme‑linked immunosorbent assay was performed to detect the expression of oxidative stress markers. Western blotting and reverse transcription‑quantitative polymerase chain reaction were used to determine the expression levels of related genes and proteins. The results revealed that RPTS enhanced cell viability and reduced H2O2‑induced oxidative stress of ARPE‑19 human retinal pigment epithelial cells. RPTS increased the MMP of ARPE‑19 cells compared with in H2O2‑treated ARPE‑19 cells. In addition, RPTS suppressed ROS production and apoptosis of H2O2‑treated ARPE‑19 cells. Additionally, RPTS modulated the expression levels of apoptosis‑associated proteins and the nuclear factor 2‑related factor 2 (Nrf2) pathway. In conclusion, RPTS alleviated H2O2‑induced oxidative stress injury by upregulating the Nrf2 pathway. The potential effects of RPTS on protection against H2O2‑induced apoptosis of ARPE‑19 cells suggested that RPTS may be a potential therapeutic target for preventing age‑related macular degeneration.


Shear rate specific blood viscosity and shear stress of carotid artery duplex ultrasonography in patients with lacunar infarction.
This study describes a new method for determining site-specific vascular shear stress using dynamic measures of shear rate and blood viscosity (BV) in the carotid arteries, and examines characteristics of carotid arterial shear stress among patients with lacunar infarction. Vascular shear stress measurements were conducted in 37 patients (17 lacunar infarction patients and 20 control subjects) using duplex ultrasonography. Vessel wall diameters and velocities were measured in each arterial segment at peak-systolic (PS) and end-diastolic (ED) phases, for calculation of PS/ED shear rates. PS/ED shear stresses [dyne/cm²] were determined with PS/ED shear rates and shear-rate dependent BV values. For comparison, both values of hematocrit-derived BV and BV measurements at 300 s⁻¹ were used for calculation of shear stress. All cardiovascular disease (CVD) risk factors including BV values were similar between the two groups. In both common carotid arteries, PS and ED shear stresses were significantly lower in the patients with lacunar infarction than in controls in multivariate models that included age, sex, and other major CVD risk factors. PS and ED shear stresses using the shear rate specific BV were 4.5% lower and 7.3% higher than those using the two other BVs, respectively. Lacunar infarction was associated with reduced carotid arterial shear stress. The use of estimated BV for calculating carotid arterial shear stress provides more accurate assessment of the hemodynamic contribution of shear stress than previous models that have arbitrarily assigned a constant value to this dynamic flow property.


An integrated neuropsychiatric approach to diagnosis and management of patients with epileptic seizures.
In patients who present to neurology settings with history of epileptic seizures, psychiatric disorders may be the sole manifestation of apparent neurologic symptoms, or they may coexist. Current challenges for clinicians include distinguishing between two disorders and making the correct diagnoses, interpreting test results, and (co-) managing the disorder(s). Our goal is to provide the clinician with an integrated neuropsychiatric approach for the triage, assessment (history, screening tools, examination, diagnostic tests), and treatment (neurologic and/or psychiatric) of these challenging patients. In particular, use of schemata, tables, and algorithms will offer step-by-step approaches and guidelines for the clinician. Recommendations are made for the indications for psychiatric consultation, and co-management is recommended for patients with emergencies, those who fail routine psychiatric treatments, and those with complex presentations or multiple comorbid conditions.


Adhesion barriers in laparoscopic myomectomy: Evidence from randomized clinical trials.
To evaluate the effectiveness of different adhesion barriers in the prevention of de novo adhesion development after laparoscopic myomectomy. A systematic review was performed by searching seven electronic databases for all randomized clinical trials (RCTs) comparing the use of any absorbable adhesion barrier (i.e. intervention group) with either no treatment or placebo (i.e. control group) in the prevention of adhesion development after laparoscopic myomectomy. Eight RCTs with a total of 748 participants (392 in the intervention group and 356 in the control group) were included. The assessed adhesion barrier methods were: oxidized regenerated cellulose (ORC) in two studies, auto-crosslinked hyaluronic acid (HA) gel in two studies, 4% icodextrin solution in one study, modified HA and carboxy-methylcellulose in one study, polyethylene glycol ester trilysine amine solution plus a borate buffer solution in one study, and polyethylene glycol amine plus dextran aldehyde polymers in another study. Adhesion barrier methods showing the most promising results were: ORC, auto-crosslinked HA gel, and polyethylene glycol amine plus dextran aldehyde polymers.


Risk assessment: theoretical considerations.
Measurements of bone mass and several other skeletal characteristics can effectively identify women at high risk for fractures. These measurements are now widely available, and other clinical data cannot provide equivalent information. Treatments exist that will preserve bone mass and presumably reduce fracture risk (although for newer treatments this requires further study). It should also be noted that the prevention of very rapid bone loss may also protect against the development of micro-architectural abnormalities, thereby further reducing risk. Even in the very old, for whom preservation of bone mass may be of less value, there now appears to be an intervention that diminishes the impact trauma associated with falls. In this group bone mass measurements may also aid in identification of the highest risk groups. It is worth noting that measurement of bone mass may further serve to motivate patients to accept or to continue with a therapy.


Recapitulating human myogenesis ex vivo using human pluripotent stem cells.
Human pluripotent stem cells (hPSCs) provide a human model for developmental myogenesis, disease modeling and development of therapeutics. Differentiation of hPSCs into muscle stem cells has the potential to provide a cell-based therapy for many skeletal muscle wasting diseases. This review describes the current state of hPSCs towards recapitulating human myogenesis ex vivo, considerations of stem cell and progenitor cell state as well as function for future use of hPSC-derived muscle cells in regenerative medicine.


Longitudinal tracking of 97 esophageal adenocarcinomas using liquid biopsy sampling.
The incidence of esophageal adenocarcinoma (EAC) is rapidly rising and has a 5-year survival rate of <20%. Beyond TNM (tumor-node-metastasis) staging, no reliable risk stratification tools exist and no large-scale studies have profiled circulating tumor DNA (ctDNA) at relapse in EAC. Here we analyze the prognostic potential of ctDNA dynamics in EAC, taking into account clonal hematopoiesis with indeterminate potential (CHIP). A total of 245 samples from 97 patients treated with neoadjuvant chemotherapy and surgery were identified from the prospective national UK Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) consortium data set. A pan-cancer ctDNA panel comprising 77 genes was used. Plasma and peripheral blood cell samples were sequenced to a mean depth of 7082× (range 2196-28 524) and ctDNA results correlated with survival. Characteristics of the 97 patients identified were as follows: 83/97 (86%) male, median age 68 years (SD 9.5 years), 100% cT3/T4, 75% cN+. EAC-specific drivers had higher variant allele fractions than passenger mutations. Using stringent quality criteria 16/79 (20%) were ctDNA positive following resection; recurrence was observed in 12/16 (75%) of these. As much as 78/97 (80%) had CHIP analyses that enabled filtering for CHIP variants, which were found in 18/78 (23%) of cases. When CHIP was excluded, 10/63 (16%) patients were ctDNA positive and 9/10 of these (90%) recurred. With correction for CHIP, median cancer-specific survival for ctDNA-positive patients was 10.0 months versus 29.9 months for ctDNA-negative patients (hazard ratio 5.55, 95% confidence interval 2.42-12.71; P = 0.0003). Similar outcomes were observed for disease-free survival. We demonstrate in a large, national, prospectively collected data set that ctDNA in plasma following surgery for EAC is prognostic for relapse. Inclusion of peripheral blood cell samples can reduce or eliminate false positives from CHIP. In future, post-operative ctDNA could be used to risk stratify patients into high- and low-risk groups for intensification or de-escalation of adjuvant chemotherapy.


Verbal episodic memory in 426 multiple sclerosis patients: impairment in encoding, retrieval or both?
Episodic memory is frequently impaired in multiple sclerosis (MS) patients but the exact nature of the disorder is controversial. It was initially thought to be due to a retrieval deficit but some studies have demonstrated an encoding deficit, which could be linked to a slowing of information processing speed or to a deficit in elaboration of strategies. The main objective of this study is to assess the prevalence and the nature of verbal episodic memory (VEM) impairment in MS patients. We retrieved memory performances of 426 patients [314 F-112 M; mean age: 46.1 years; median Expanded Disability Status Scale (EDSS) score: 3.1] from a neuropsychological data base. VEM was assessed using the 16 words RL-RI 16 test. 66% MS patients present at least one recall impaired in VEM (37.2% from 2 to 5 recall). 14.2% MS patients present an impairment in encoding phase. We observed that 5% of patients presented recognition difficulties. Correlations were observed between VEM performances and EDSS, and disease duration but no group effect (ANOVA) is observed between form of MS and VEM performances. These results confirm the high prevalence of VEM impairment in MS patients. Deficits affect mainly information retrieval in early stage MS patients and are then linked to encoding as disability increases. Storage disorders are infrequent, so cognitive rehabilitation with mental imaging could be effective in MS patients.


Outcome comparison of radical prostatectomy versus seed brachytherapy for clinically localized prostate cancer using two biochemical recurrence definitions.
We compared the outcome of radical prostatectomy (RP) with seed brachytherapy (BT) in clinically localized prostate cancer (LPCa) using two different biochemical recurrence (BCR) definitions. Clinical data of 1117 patients with non-metastatic prostate cancer (PCa) treated with either RP or BT as the basis of the multimodal therapy from a single tertiary hospital between 2007 and 2021 were retrospectively analyzed. 843 LPCa patients (RP = 737, BT = 106) with at least one prostate-specific antigen (PSA) test after treatment were finally included. The BCR survival was evaluated by direct comparison and one-to-one propensity score matching (PSM) analysis using surgical definition (PSA ≥ 0.2ng/ml) for RP and surgical/Phoenix definition (PSA nadir + 2ng/ml ) for BT. The propensity score (PS) was calculated by multivariable logistic regression based on the clinicopathological parameters. Median follow-up was 43 months for RP patients and 45 months for BT patients. Kaplan-Meier analysis did not show any statistically significant differences in terms of BCR-free survival (BFS) between the two groups when using Phoenix definition for BT (P > 0.05). Similar results were obtained in all D'Amico risk groups when stratified analyses were conducted. However, RP achieved improved BFS compared to BT in the whole cohort and all risk groups with the surgical definition for BT(P < 0.05). After adjusting PS, 192 patients were divided into RP and BT groups (96 each). RP presented a better BFS than BT when using the surgical definition (P < 0.001), but no significant difference was found when using the Phoenix definition (P = 0.609). Inconsistent BCR-free survival outcomes were acquired using two different BCR definitions for BT patients. RP provided comparable BFS with BT using the Phoenix definition but better BFS using the surgical definition, regardless of whether the PSM was performed. Our findings indicated that an exact BCR definition was critical for prognostic assessment. The corresponding results will assist physicians in pretreatment consultation and treatment selection.


[Postoperative Delirium in Patients on Cardiopulmonary Bypass for Cardiovascular Surgeries: Incidence and Influencing Factors].
To investigate the incidence and influencing factors of postoperative delirium (POD) and subsyndromal delirium (SSD) in patients connected to cardiopulmonary bypass during cardiovascular surgeries. We collected the general data and the data for the perioperative hematological, physiological, and biochemical indicators and the surgical and therapeutic conditions of patients connected to cardiopulmonary bypass during the course of cardiovascular surgeries conducted at a tertiary-care hospital in Hubei province between May 2022 and September 2022. The outcome indicators, including the incidence of POD and SSD, were assessed with the Nursing Delirium Screening Scale (Nu-DESC). Multinomial logistic regression was performed to analyze the influencing factors of patients with different statuses of POD and SSD. Among the 202 patients, the incidence of SSD, SSD progressing to POD, and no POD or SSD (ND) progressing to POD were 13.4%, 6.4%, and 34.2%, respectively. Regression analysis showed that, with ND patients as the controls, the influencing factors for SSD were preoperative blood glucose (odds ratio [ OR]=0.38, 95% confidence interval [ CI]: 0.19-0.76), intraoperative platelet transfusion ( OR=0.37, 95% CI: 0.15-0.92), intraoperative etomidate ( OR=0.93, 95% CI: 0.87-0.98), and postoperative total bilirubin level ( OR=1.04, 95% CI: 1.01-1.07). For the progression of SSD to POD, the influencing factors were age ( OR=1.09, 95% CI: 1.01-1.17), ASA classification of IV and above ( OR=10.72, 95% CI: 1.85-62.08), intraoperative dexmedetomidine ( OR=1.01, 95% CI: 1.003-1.02), and the duration of mechanical ventilation ( OR=1.04, 95% CI: 1.01-1.07). For the progression of ND to POD, the influencing factors were age ( OR=1.06, 95% CI: 1.02-1.10), middle or high school education ( OR=0.35, 95% CI: 0.15-0.83), and the duration of mechanical ventilation ( OR=1.04, 95% CI: 1.01-1.07). Age, education, ASA classification, preoperative blood glucose, intraoperative platelet transfusion, intraoperative etomidate, intraoperative dexmedetomidine, postoperative total bilirubin, and the duration of mechanical ventilation are influencing factors for different statuses of POD and SSD among patients connected to cardiopulmonary bypass when they are undergoing cardiovascular surgeries. The influencing factors vary across groups of patients with different statuses of POD and SSD. Therefore, we should accurately assess the risk factors of patients with different statuses of POD and SSD and carry out corresponding interventions, thereby preventing or reducing the occurrence of POD and SSD, and ultimately promoting enhanced recovery after surgery.


Variations in and significance of systolic pressure during maximal exercise (treadmill) testing.
Variations in clinical noninvasive systolic pressure at the point of symptom-limited exercise on a treadmill were examined in six groups of subjects: 5,459 men and 749 women classified into three categories each. Among the men, 2,532 were asymptomatic healthy, 592 were hypertensive and 1,586 had clinical manifestations of coronary heart disease (that is, typical angina pectoris, prior myocardial infarction or sudden cardiac arrest with resuscitation). Among the women, 244, 158 and 347 were in the corresponding clinical categories. None had had cardiac surgery; all had follow-up status ascertained by periodic mail questionnaires. Reported deaths were reviewed and classified by three cardiologists; 140 deaths were attributed to coronary heart disease, 118 of them in the men classified as having coronary heart disease. The majority of maximal systolic blood pressure readings were reported to the nearest centimeter rather than millimeter of pressure. Retesting of 156 persons from 1 to 32 months later showed that pressure values agreed within 10 percent in two thirds, the overall mean difference was only 8.6 mm Hg and the correlation at maximal exercise was superior to that of the resting observations just before exercise. Hypertensive patients had a significantly greater body weight than normotensive persons. Among men, the lowest maximal systolic pressure was observed in the group with coronary heart disease; among women, the lowest mean pressure was found in the healthy group. Patients with coronary heart disease were slightly older, and only the women showed a significant correlation in maximal pressure with age. Only 5 percent of the variation in maximal systolic pressure in the patients with coronary heart disease was due to a shortened duration of exercise. Maximal systolic pressures correlated fairly well (r equals 0.46 to 0.68 for the various groups) with resting systolic pressure, and this relation was independent of the diagnosis of cardiovascular disease in both men and women. Relations between pressure and the number of stenotic coronary arteries and imparied ejection fraction at rest were examined in 22 men without and 182 men with coronary artery disease. Lower maximal systolic pressures were often associated with two or three vessel disease or reduced ejection fraction, or both. The prognostic value of maximal systolic pressure for subsequent death due to coronary heart disease was examined in the men with coronary heart disease. The annual rate of sudden cardiac death decreased from 97.9 per 1,000 men to 25.3 and 6.6 per 1,000 men as the range of maximal systolic pressure increased from less than 140 to 140 to 199 and to 200 mm Hg or more, respectively. Cardiomegaly, Q waves in the resting electrocardiogram and persistent postexertional S-T depression were more common in men with the lowest systolic pressure at maximal exercise.


Afferent fibres from muscle receptors in the posterior nerve of the cat's knee joint.
The properties of some receptors with afferent fibres in the cat's posterior knee joint nerve have been examined, especially those discharging tonically with the joint in intermediate positions between full flexion and extension. Some of these receptors behave like muscle spindles, and respond to manoeuvres which stretch popliteus muscle. Both in single unit and whole nerve recordings their discharge pauses during a popliteus twitch, and can be strikingly augmented by tetanic stimulation of a number of popliteus fusimotor fibres isolated from ventral root filaments. The action of succinylcholine on these receptors closely resembles its effect on popliteus spindle units with fibres sited normally in the popliteus nerve. Other units with properties suggesting origin from popliteus tendon organs were also observed; their fibres and those of the spindle units conducted at Group I velocity. It is concluded that some afferent fibres from popliteus spindles and possibly tendon organs commonly pursue an aberrant course in the posterior articular nerve of the knee joint.


Synthesis and molecular structure of 14,15-pyrrolidino-and 14,16-ethano derivatives of estrone.
Hydrolysis of 3-methoxy-16alpha-nitro-14,17-ethenoestra-1,3,5(10)-trien-17beta-yl acetate under weakly basic conditions leads to formation of 3-methoxy-2'-oxopyrrolidino-[4',5':14beta,15beta]-estra-1,3,5 (10)-trien-17-one, the structure of which has been confirmed by X-ray analysis and some chemical transformations. The reactivity of 3-methoxy-16alpha-nitro-14,17-ethanoestra-1,3,5(10)-trien-17beta-yl acetate under various conditions of basic hydrolysis has been investigated. The derived compounds have been identified by means of NMR spectroscopy and X-ray analysis.


PEEP decreases oxygenation of the intestinal mucosa despite normalization of cardiac output.
To evaluate if normalization of cardiac output reverses the attenuation of local intracapillary hemoglobin saturation (HbO2) of gastric mucosa by PEEP (positive end-expiratory pressure) during IPPV (intermittent positive pressure ventilation). Four healthy, chronically instrumented, anesthetized dogs were repeatedly studied (n = 7). Local HbO2 of gastric mucosa was measured continuously by tissue lightguide spectrophotometry and cardiac output (CO) was recorded continuously by means of a precalibrated ultrasonic transit time flowmeter chronically implanted around the pulmonary artery. After obtaining baseline values during IPPV and ZEEP (zero end-expiratory pressure) 15 cmH2O PEEP was added. To compensate the reduction of CO during PEEP ventilation, HES (hydroxyethyl starch 6%) was infused until CO reached baseline values during ZEEP. Despite of unimpaired systemic oxygen saturation, PEEP reduced HbO2 of gastric mucosa from 55.1 +/- 4.2% to 42.1 +/- 4.7% (mean +/- SEM) and CO dropped from 67.7 +/- 4.9 ml.kg-1.min-1 to 33.9 +/- 4.6 ml.kg-1.min-1. Whereas infusion of HES during PEEP ventilation normalized CO to 65.1 +/- 6.2 ml.kg-1.min-1, HbO2 reached only 48.1 +/- 3.3%, a statistically significant improvement compared to HbO2 during PEEP ventilation before HES infusion (p < 0.03, Wilcoxon signed rank test), but still below baseline values (p < 0.04). Our findings demonstrate that the side effects of PEEP ventilation on cardiac output can be compensated by restoring preload, but normalizing CO did not completely normalize HbO2 of the gastric mucosa. This further emphasizes that global measurements of variables of systemic circulation and oxygenation do not necessarily reflect regional abnormalities of tissue oxygenation. Therefore, in view of the importance of tissue hypoxia especially in the splanchnic region in the pathogenesis of multiple organ failure, monitoring of HbO2 of the intestinal mucosa during PEEP ventilation may be particularly useful in the care of the critically ill patient.


Screening of male patients with autism spectrum disorder for creatine transporter deficiency.
Creatine deficiency syndromes (CDS) are newly identified genetic disorders that result in neurological impairment of cognition and communication. The purpose of our study was to screen 100 male subjects with autism spectrum disorder for mutations in the SLC6A8 gene in order to determine the frequency of this genetic disorder in this population. One hundred males ages 3-18 years diagnosed with autism spectrum disorder based on DSM-IV criteria were recruited. DNA sequence analysis was performed on all subjects for creatine transporter gene (SLC6A8) defects. One subject had a novel unclassified variant in the SLC6A8 gene exon 13: c.1890G>C. Given that autistic features are found in a number of patients with CDS, SLC6A8 deficiency as well as the treatable forms of CDS should be included in the differential diagnosis of patients with autism spectrum disorder.


Improvement of cerebral blood flow following stereotactic surgery in patients with putaminal haemorrhage.
Changes in cerebral blood flow (CBF) after CT guided stereotactic aspiration of putaminal haematoma were investigated in 13 patients with Xe-133 inhalation and single photon emission computed tomography. The interval from onset to operation ranged from 13 to 82 days (mean 30 days). The mean estimated haematoma volume ranged from 20 to 50 ml (mean 31.9 ml). The percentage of haematoma aspirated ranged from 75 to 98% (mean 86.8%). Postoperative CBF in two thirds of the patients was improved even though all cases were operated on in the subacute stage. Both the mean hemispheric and regional CBF in the anterior territory of the middle cerebral artery and in the region of the thalamus and basal ganglia in the affected hemisphere were increased postoperatively. Also in the nonaffected hemisphere, regional CBF in the region of the thalamus and basal ganglia was improved.


The effects of stress on the development of immunological memory following low-dose antigen priming in mice.
Observable stress effects on immune responses may be a function of the quantitative and qualitative characteristics of the stressor, and the outcome measurement of immunity. Further, the effects of stress on humoral immunity, in particular, may be sensitive to the concentrations of antigen used to elicit a response. We have studied the effects of footshock stress during the time of priming with low concentrations of antigen on the secondary response to another low dose of antigen. The secondary humoral immune response of C3H/HeJ mice to the protein antigen keyhole limpet hemocyanin was examined following footshock, exposure to the apparatus without shock, or exposure to the home cage. Footshock reproducibly depressed the IgG anti-KLH response, and the effect on the IgM response was sporadic. Initially, footshock was administered for 7 days before and 7 days after priming with low amounts of antigen. Subsequent studies demonstrated that a single footshock session delivered 24 h after priming could suppress the IgG anti-KLH response.


Potential toxicity of landfill leachate to zebrafish and mung beans.
Landfill leachate has become a major public health concern due to its adverse health effects. However, its toxicological effects have not been thoroughly determined because of its complex composition. To address this issue, two model organisms were used in this study, including mung beans and zebrafish. Bean seedlings were exposed to different concentrations of landfill leachate (1%, 5%, 10%, 15%, and 20%, v/v, leachate/deionized water) for 7 days. Low concentrations (1%) of landfill leachate increased the growth of mung beans, whereas high concentrations (15% and 20%) of landfill leachate inhibited the growth and development of seedlings. Furthermore, landfill leachate reduced chlorophyll levels but increased malondialdehyde levels, leading to an increased rate of root-tip micronuclei. Zebrafish embryos were exposed to different concentrations of landfill leachate (0.5%, 1.0%, 1.2%, and 1.5%, v/v, leachate/E3 medium) for 120 h. The results showed that landfill leachate significantly decreased lower levels of hatching rate and heart rate but increased the mortality and malformation rates of embryos. Moreover, 1.0% landfill leachate reduced the frequency of spontaneous movement and the light stimulation reaction of embryos. Embryos exposed to leachate showed less exploratory behavior and fewer mirror attacks in the black and white areas. Our results suggest that exposure to landfill leachate could cause developmental toxicity and genotoxicity in plants and fish. The findings can improve our understanding of the environmental toxicity of landfill leachate and provide additional evidence for its risk assessment and management.


Food Retailers and Obesity.
We live in an 'obesogenic environment' where we are constantly bombarded with choices that encourage us to move less and eat more. Many factors influence our dietary choices, including the expert marketers who advise manufacturers on ways to encourage the population to buy more, especially profitable, palatable 'ultra-processed' foods. Supermarkets themselves have become skilled in manipulating buying behaviour, using their layout and specific product placement as well as advertising to maximise purchases of particular foods. Increasingly, supermarkets push their own 'house' brands. Those marketing fast foods also use persuasive tactics to attract customers, especially children who they entice with non-food items such as promotional or collectable toys. There is no mystery to the increase in obesity: our energy intake from foods and drinks has increased over the same period that energy output has decreased. Obesity has a range of relevant factors, but there is little doubt that marketing from supermarkets and fast food retailers has played a role.


Perinatal pulmonary hyperplasia due to laryngeal atresia.
A premature newborn boy, who died at birth because of cartilaginous laryngeal atresia, showed lung development that was far more advanced than normal for gestational age. The lungs, which were histologically normal, were three times the expected weight and showed a degree of alveolarization appropriate for 3 months' postnatal age. The lungs crowded the chest cavity so that the diaphragm was flattened and immobilized; the massive ascites, documented by ultrasound 5 weeks prior to delivery, appeared to be due to obstructed venous return. Thus, the pulmonary hyperplasia, a new finding in perinatal pathology, caused severe fetal ascites. Subsequently, the hyperplasia led to acute polyhydramnios that, ultrasonographically, was observed to develop 2 weeks prior to delivery. The observation that fetal lungs may be hyperplastic has a bearing on the known relationship between fetal lung growth and retention of lung fluid.


Decreased expression of the human folate receptor mediates transport-defective methotrexate resistance in KB cells.
The human membrane-associated folate binding protein, or folate receptor (hFR), is a necessary component of folate and methotrexate (MTX) transport in some cell lines. To investigate the role of hFR in acquired MTX resistance in human cells, we characterized nine MTX-resistant clones selected from human nasopharyngeal epidermoid carcinoma (KB) cells (cells which transport folates/anti-folates via the hFR) cultured in media containing low folate concentrations. Compared with wild type KB cells, the level of resistance of the clones ranges from 2- to 80-fold higher and the resistant phenotypes of the clones are characterized as follows. 1) DHFR levels are increased (3-13-fold) in four of nine clones; 2) MTX polyglutamation is not detectably different; 3) the extents of MTX efflux are similar; 4) initial rates of MTX efflux are similar except for two clones which exhibit slightly faster efflux rates (approximately 2-fold); and 5) the Vmax for specific MTX and 5-methyltetrahydrofolate transport are decreased (2-18-fold) in all mutants. The Kt values for MTX transport of each mutant are similar to the Kt of KB cells. These results indicate that all nine MTX-resistant clones exhibit defective MTX transport and that four clones also have increased DHFR levels. Based on folic acid binding assays, the hFR is reduced by 1.8-24-fold in these clones relative to KB cell hFR expression. Western, Northern, and Southern analyses are consistent with decreased hFR expression in these clones rather than mutations, resulting in alterations in the size or ligand binding affinities of the hFR. The decrement in hFR expression correlates closely with the degree of reduction in MTX transport Vmax for each clone. Since folate and MTX influx proceed via hFR in KB cells and in these mutants, the correlation (R2 = 0.90) between hFR expression and the MTX transport Vmax of each clone indicates that hFR expression is an important determinant of acquired MTX resistance in this human tumor cell line. These studies demonstrate that defective transport (manifested by decreased Vmax) resulting from decreased expression of the hFR is frequent in KB cells cultured under these conditions and suggest that modulation of hFR may be relevant to MTX cytotoxicity or resistance in tissues or cells expressing functionally significant levels of hFR.


Does modified Otago Exercise Program improves balance in older people? A systematic review.
Exercise interventions focused on strength and balance are effective for falls prevention in older people, however compliance to exercise is often a problem. Tailored intervention programs are recommended to meet the person preferences and increase compliance. Otago Exercise Program (OEP) is the most disseminated fall prevention program and is individually prescribed at home. The purpose of this study was to identify OEP modified formats and investigate their effects on balance when compared to its original form of delivering. Four electronic databases were searched, PubMed, PEDro, Science Direct and Scopus, between January and February 2017. Eligibility criteria included experimental or qualitative design studies conducted among older adults (≥50 years) at risk of falling, ongoing exercise interventions with modified formats of OEP. The primary outcome was balance. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used. Eight studies met the inclusion criteria, five were randomized controlled trials (RCTs), two were quasi-experimental and one was a qualitative study. Therefore, a qualitative analysis was performed. Modified formats of OEP included additional vestibular or multisensory balance exercises, augmented reality, exercise in group and a DVD delivering format (in group or individual). In general, all studies using OEP modified formats reported improvements on balance and functional ability. However, it remains unclear if it is as effective as the original OEP and which modified format is more effective.


A pair of epimeric 13-hydroxy-2,3,6,7-tetramethoxy-8b,11,12,12a,13,13a-hexahydro-9H-9a-azacyclopenta[b]triphenylene-10-ones.
The structures of two compounds which are intermediates in the synthesis of phenanthroindolizidine alkaloids have been determined. (8bS,13aS,14R,14aR)-8b,9,11,12,13,13a,14,14a-Octahydro-14-hydroxy-2,3,6,7-tetramethoxydibenzo[f,h]pyrrolo[1,2-b]isoquinolin-11-one acetone solvate, C24H27NO6.C3H6O, (II), crystallizes in a chiral space group with one solvent molecule (acetone) present in the asymmetric unit. On the other hand, (8bS,13aS,14S,14aR)-8b,9,11,12,13,13a,14,14a-octahydro-14-hydroxy-2,3,6,7-tetramethoxydibenzo[f,h]pyrrolo[1,2-b]isoquinolin-11-one, C24H27NO6, (III), crystallizes in a centrosymmetric space group with two molecules in the asymmetric unit and with no solvent present. The two molecules in the asymmetric unit of (III) are structurally the same. Compounds (II) and (III) are epimers at the C atom carrying the OH group; otherwise they are very similar in structure.


Imagery rehearsal treatment for chronic nightmares.
Fifty-eight chronic nightmare sufferers were randomly assigned to two groups: treatment (n = 39) and wait-list control (n = 19). Treated Ss were taught a cognitive-behavioral technique called imagery rehearsal in which they learned in a waking state to change a nightmare and then to visualize the new set of images. Subjects were assessed pre-treatment and 3 months followup for nightmare frequency, self-rated distress and subjective sleep quality. Compared to controls, the treatment group showed significant and clinically meaningful decreases in nightmares. Treated Ss decreased nightmares as measured in nights/week (mean = -2.0, SD = 1.7, P = 0.0001) and actual number of nightmares (mean = -4.2, SD = 4.5, P = 0.0001). Significant improvement in self-rated sleep quality occurred in those treated compared with controls (P = 0.004); and, reduction in nightmares was a significant predictor of improvement in sleep (r = 0.55, P = 0.0001). These preliminary results lend support to the theory that, for some chronic sufferers, nightmares may be conceptualized as a primary sleep disorder which can be effectively and inexpensively treated with cognitive-behavioral therapy.


Structures of L-BC virus and its open particle provide insight into Totivirus capsid assembly.
L-BC virus persists in the budding yeast Saccharomyces cerevisiae, whereas other viruses from the family Totiviridae infect a diverse group of organisms including protists, fungi, arthropods, and vertebrates. The presence of totiviruses alters the fitness of the host organisms, for example, by maintaining the killer system in yeast or increasing the virulence of Leishmania guyanensis. Despite the importance of totiviruses for their host survival, there is limited information about Totivirus structure and assembly. Here we used cryo-electron microscopy to determine the structure of L-BC virus to a resolution of 2.9 Å. The L-BC capsid is organized with icosahedral symmetry, with each asymmetric unit composed of two copies of the capsid protein. Decamers of capsid proteins are stabilized by domain swapping of the C-termini of subunits located around icosahedral fivefold axes. We show that capsids of 9% of particles in a purified L-BC sample were open and lacked one decamer of capsid proteins. The existence of the open particles together with domain swapping within a decamer provides evidence that Totiviridae capsids assemble from the decamers of capsid proteins. Furthermore, the open particles may be assembly intermediates that are prepared for the incorporation of the virus (+) strand RNA.


Different Treatment Strategies for Patients with Multivessel Coronary Disease and High SYNTAX Score.
We sought to evaluate the prognosis of different treatment strategies on patients with multivessel coronary disease and high SYNTAX score. 171 patients with multivessel coronary disease and SYNTAX score ε33, who underwent coronary angiography between July 2009 and July 2010 at our hospital were retrospectively selected and divided into incomplete and complete revascularization intervention groups (IR), a coronary artery bypass surgery group (CABG), a conservative drug therapy group according to treatment strategies chosen and agreed by the patients. These patients were followed up for 19.44 ± 5.73 months by telephone or outpatient service. We found the medical treatment group has a lower overall survival than the IR, CR group, and CABG group (P log-rank values are 0.03, 0.03, and 0.02, respectively). The medical treatment group also has a lower survival than the IR group, CR group, and CABG group in cerebral stroke and recurrent myocardial infarction (MI) (P log-rank values are 0.004, 0.03, and 0.001, respectively) and MACE events (P log-rank values are 0.003, 0.001 and P < 0.001, respectively). The medical treatment group and IR group have lower survival in recurrent angina pectoris than the CR group and CABG group (P log-rank values are 0.02, 0.02 and 0.03, 0.008, respectively). There are no significant differences between the CR group and the CABG group in number of deaths, strokes and recurrent MIs, MACE events, angina pectoris (P log-rank values are 0.69, 0.53, and 0.86, respectively). The IR group shows a lower survival than the CR group and CABG group only in angina pectoris (P log-rank values are 0.03 and 0.008, respectively). For the patients with a high SYNTAX score, medical treatment is still inferior to revascularization therapy (interventional therapy or coronary artery bypass surgery). It appears that the CABG is not obviously superior to the coronary intervention therapy. Complete revascularization and coronary artery bypass grafting treatments simply have better survival in angina pectoris compared to the incomplete revascularization. Therefore, individual treatment strategies are recommended and more trials are required to study these effects.


Outcomes of pregnancy in women with autoimmune hepatitis.
Optimal management during pregnancy of patients with autoimmune hepatitis (AIH) remains undefined. We therefore reviewed all patients with AIH who reported pregnancy at our centre to identify any pre-conception factors that might predict adverse outcomes. There were 81 pregnancies in 53 women. Median age at conception was 26 years (range 16-42); with 41% of pregnancies occurring in the context of cirrhosis. At conception, 61 patients (75%) were on therapy for AIH. The live birth rate (LBR) was 73% (59/81). Prematurity, occurred in 12/59 (20%) and 6 (11%) required admission to special care baby unit (SCBU). In mothers who were cirrhotic at the time of conception the LBR was lower (p = 0.02) and need for admission to SCBU was higher. The overall maternal complication rate was 31/81 (38%) conceptions. A flare in disease activity occurred in 26/81 (33%) pregnancies. A serious maternal adverse event (death or need for liver transplant) during or within 12-months of delivery, or hepatic decompensation during or within 3-months of delivery, occurred with 9 pregnancies (11%) and was more common in women with cirrhosis (p = 0.028). Maternal therapy had no significant impact on the LBR (p = 0.24), termination rate (p = 0.72), miscarriage rate (p = 0.19) or gestational period (p = 0.8). Flares in AIH were more likely in patients who were not on therapy (p = 0.048) or who had a disease flare in the year prior to conception (p = 0.03). Patients who had a flare in association with pregnancy were more likely to decompensate from a liver standpoint (p = 0.01). This study demonstrates that poor disease control in the year prior to pregnancy and the absence of drug therapy are associated with poor outcomes whist pregnant. These data should facilitate appropriate pre-conception counselling and appropriate pregnancy management in this cohort.


Late Reconstruction of the Orbit With Patient-Specific Implants Using Computer-Aided Planning and Navigation.
Reconstruction of orbital deformities is a challenging task. Virtual 3-dimensional (3D) planning and the use of patient-specific implants (PSIs) could improve anatomic and functional outcomes in the orbital region. A retrospective study was performed of patients who underwent late orbital reconstruction from 2009 to 2013. To be included in the study, patients had a unilateral orbital deformity by involvement of at least 2 orbital wall defects. No orbital osteotomies could be used to correct the deformity. All patients underwent 3D virtual treatment planning. The unaffected orbit was mirrored onto the affected orbit. The PSI was fabricated according to this plan. Navigation was used to check the implant position. Six patients were included in this study. All patients had diplopia or motility limitations and enophthalmos. The ophthalmic parameters showed improvement in all patients. Enophthalmos was corrected adequately by the PSI. Four patients received a poly-ether-ether-ketone PSI. Two patients received a titanium mesh PSI. The position of the PSI was controlled by intraoperative navigation. Superimposition of the planned and postoperative positions of the PSI showed good correlation. PSIs placed with intraoperative navigation facilitate late or secondary correction of orbital deformities.


Altered protein conformation on DNA binding by Fos and Jun.
The protein products of the c-fos and c-jun proto-oncogenes (Fos and Jun, respectively) form a heterodimeric protein complex that interacts with the activator protein-1 (AP-1) binding site and regulates gene transcription in response to extracellular stimuli. Protein dimerization is mediated primarily by a coiled-coil-like structure termed the leucine-zipper and DNA binding occurs primarily through regions of each protein rich in basic amino acids that contact both strands of the AP-1 site. The precise nature of the protein-DNA interaction is unknown as studies concerned with dimerization and DNA binding by Fos and Jun have relied on indirect methods to investigate protein-protein-DNA interactions. Here we have developed assay systems using fluorescence spectroscopy and circular dichroism to monitor dimerization and DNA binding directly. The results indicate that the interaction of Fos and Jun with DNA results in an altered conformation of the protein dimers and an increased alpha-helical content. These techniques may have general application in studies concerning the interaction of transcriptional regulatory proteins with specific DNA target sequences.


Long-term physical exercise retards trabecular bone loss in lumbar vertebrae of aging female mice.
The present study examined the effect of long-term, moderate physical exercise on trabecular bone volume (TBV), calcium content, 3H-proline uptake, and the activities of alkaline and acid phosphatases in lumbar vertebrae of aging and senescent mice. It became apparent that if physical activity starts at an early stage of life, i.e., prior to middle age and is extended until old age, it exerts beneficial effects on trabecular bone mass and mineralization. Such a positive effect is not obtained if the training program is initiated after middle age. The training-induced reduction in bone loss was accompanied by a significant decrease in acid phosphatase activity whereas no changes took place with regard to the activity of alkaline phosphatase. Long-term physical exercise also enhanced the uptake of 3H-proline by lining cells along the bone trabecules. In spite of its moderate nature, the endured training program served as a stress factor for the involved animals, a fact that was manifested by an increase in the serum levels of corticosterone. Thus, it seems that whereas young animals respond favorably to such a stimulatory stress, older animals lose this ability of adaptation.


Primary neoplasms of the small bowel.
The treatment of thirty-one malignant and eleven benign neoplasms of the small intestine is reported. The most common symptom was abdominal pain followed by vomiting, diarrhea, weight loss, constipation, and gastrointestinal bleeding. In four cases small bowel perforated. Intestinal obstruction occurred in 31 per cent of patients. Preoperative diagnosis was made in 19 per cent of patients. All eleven patients with benign neoplasms were curatively treated by resection and primary anastomosis. Eighteen of the thirty-one patients with malignant tumors had curative resection, five had palliative resection, and eight had laparotomy and biopsy only. The most common benign tumor was leiomyoma. The most common malignant tumor was lymphoma (67 per cent) followed by adenocarcinoma (16 per cent), carcinoid (10 per cent), and leiomyosarcoma (3 per cent). Twenty-four patients were available for follow up; thirteen remain alive and eleven died, seven within one year and four within two years.


The combined effect of reduced fossil fuel consumption and increasing biomass combustion on Athens' air quality, as inferred from long term CO measurements.
To evaluate the role of biomass burning emissions, and in particular of residential wood heating, as a result of the economic recession in Greece, carbon monoxide (CO) atmospheric concentrations from five (5) stations of the National Air Pollution Monitoring Network in Athens, spanning the period 2000-2015, in conjunction with black carbon (BC) concentrations from the NOA (National Observatory of Athens) station at Thissio were analysed. The contribution of the different sources to the diurnal cycle of these two pollutants is clear, resulting to a morning peak, mainly due to traffic, and a late evening peak attributed both to fossil fuel (traffic plus central heating) and biomass combustion. Calculated morning and evening integrals of CO peaks, for the investigated period, show consistent seasonal modulations, characterised by low summer and high winter values. The summer and winter morning CO peak integrals demonstrate an almost constant decreasing trend of CO concentrations over time (by almost 50% since 2000), attributed to the renewal of passenger car fleet and to reduced anthropogenic activities during the last years. On the other hand, an increase of 23%-78% (depending on the monitoring site) in the winter evening integrals since 2012, provides evidence of the significant contribution of biomass combustion, which has prevailed over fossil fuel for domestic heating. CO emitted by wood burning was found to contribute almost 50% to the total CO emissions during night time (16:00-5:00), suggesting that emissions from biomass combustion have gained an increasing role in atmospheric pollution levels in Athens.


Association of polymorphisms at DGAT1, leptin, SCD1, CAPN1 and CAST genes with color, marbling and water holding capacity in meat from beef cattle populations in Sweden.
The objective of this study was to investigate the associations of single nucleotide polymorphisms (SNPs) at five candidate genes with meat pH, color, marbling and water holding capacity (WHC) in young bulls from five beef breeds (n=243) in Sweden. The UASMS2 polymorphism at the leptin gene and the SNPs at the Stearoyl-CoA desaturase 1 gene (SCD1.878) and μ-calpain gene (CAPN1:c.947) were associated with variation in meat color traits after 6days of exposure to air. The K232A polymorphism at the diacylglycerol O-acyltransferase 1 (DGAT1) gene and the CAPN1:c.947 SNP were associated with level of beef marbling. There was no association between the SNP at the calpastatin gene (CAST:c.155) and meat quality traits, nor was there any association of the tested SNPs with WHC traits and pH value.


[SI-units in radiotherapy and radiation protection (author's transl)].
A review is given about SI units as they will be used in future in radiotherapy and health physics. The paper includes conversion tables for the units used in these fields and presents some somments on possible difficulties by using these units in practical work.


Potential of the non-weight-bearing tunnel view in diagnosing medial meniscus posterior root tear: a pilot study of X-ray characteristics.
Early detection of medial meniscus posterior root tear (MMPRT) is important in preventing the rapid onset and progression of degenerative knee disease. Diagnosis is facilitated by the availability of non-weight-bearing X-ray view, but information on the X-ray characteristics of MMPRT is scarce. Here, we conducted a pilot study of the X-ray characteristics of MMPRT on non-weight-bearing tunnel view. We retrospectively reviewed 43 consecutive patients treated in the outpatient department for medial knee pain or popliteal pain. Patients were divided into MMPRT (21 knees) and non-MMPRT groups (22 knees). We investigated X-ray characteristics and magnetic resonance imaging findings. Femorotibial angle, posterior tibial slope, medial tibial eminence (MTE)-medial femoral condyle (MFC) distance (contralateral and affected sides, and difference between the two), medial tibiofemoral joint (MTFJ) width (contralateral and affected sides, and difference between the two), and meniscus radial dislocation between the groups were evaluated using the Mann-Whitney U test. The association between X-ray characteristics and MMPRT was determined using univariate and multivariate logistic regression analyses. A highly significant difference between the affected and contralateral sides was seen in MTFJ width and MTE-MFC distance on non-weight-bearing tunnel view between the MMPRT and non-MMPRT groups. Moreover, a difference in MTFJ width of <-0.575 mm and in MTE-MFC distance of >0.665 mm between the affected and contralateral sides was useful in predicting MMPRT. The non-weight-bearing tunnel view is useful for the initial diagnosis of MMPRT. Prospective evaluation in a larger population is warranted.