Altered balance between Th1 and Th17 cells in circulation is an indicator for the severity of murine acute GVHD.
Disbalance of Th1 and Th17 can lead to inflammatory diseases and autoimmunity. Acute graft-versus-host disease (GVHD) is now considered as a compound and dysregulated immune response. Both Th1 and Th17 have been implicated in the pathophysiology of acute GVHD. Disbalance of Th1 and Th17 may also play a critical role in mediating acute GVHD. In this study, we investigated the Th1/Th17 imbalance in peripheral blood through out the pathological process of acute GVHD, using a GVHD model of C57BL/6 (H-2(b)) donor to BALB/c (H-2(d)) recipient. We also analyzed the correlation between Th1/Th17 ratio and severity of acute GVHD, and explored the potential function of Th1/Th17 imbalance in acute GVHD. Recipients received 5×10(6) spleen cells (SP) underwent more severe acute GVHD, compared with the ones received 5×10(5) SP. Severe GVHD bearing recipients had much higher proportion of Th1 cells but lower proportion of Th17 cells, compared with mild GVHD bearing ones. The Th1/Th17 ratios in both groups underwent relative changes according to the changing proportions of Th1 and Th17 cells and showed positive correlation with clinical scores of acute GVHD. We describe the changing proportions of Th1 and Th17 cells in acute GVHD, and we find that Th1/Th17 ratio is an accurate indicator for predicting the severity of acute GVHD.


Role of the peripheral vasculature in changes in venous return caused by isoproterenol, norepinephrine, and methoxamine in anesthetized dogs.
We studied effects on venous return of alpha- and beta-adrenergic agonists in anesthetized dogs. Blood from the superior and inferior venae cavae (venous return) was drained at the level of the tricuspid valve into a reservoir, from which blood was pumped into the right atrium at a constant rate. Isoproterenol infused into the ascending aorta or the right atrium increased the venous return and heart rate and decreased systemic blood pressure. The increase in venous return produced by isoproterenol given into the right atrium was not significantly different from that produced by isoproterenol administered into the ascending aorta, although the increase in heart rate was more marked with the latter route of administration. Norepinephrine infused into the ascending aorta increased the systemic blood pressure, venous return, and heart rate. Methoxamine infused into the ascending aorta increased the systemic blood pressure and decreased the venous return but produced no change in heart rate. Isoproterenol increased the venous return even when the sinoaortic baroreceptor reflex was eliminated. Propranolol abolished the increase in venous return caused by isoproterenol and reversed the increase in venous return caused by norepinephrine. The results suggest that a decrease in venous resistance mediated through a beta-adrenergic mechanism is important in increasing venous return, whereas an increase in venous resistance mediated through an alpha-adrenergic mechanism is responsible for a decrease in venous return.


Antiestrogenic activities of Ginkgo biloba extracts.
Most climacteric and postmenopausal women appear to have vasomotor symptoms as well as a high risk of osteoporosis and cardiovascular disease. Although exogenous estrogens can reduce these symptoms, women are reluctant to use hormone replacement therapy (HRT) due to its undesirable side effects, such as irregular bleeding and an increased risk of breast cancer. A previous study suggested that Ginkgo biloba extracts (GBE) have estrogenic activity and might be suitable as an alternative to HRT. However, there are no reports of the preventive effect of GBE on breast cancer, which is the side effect of classical HRT. In this study, it was confirmed that GBE exhibits estrogenic and antiestrogenic activity depending on the E2 and GBE concentration, via estrogen receptor (ER)-dependent and ER-independent pathways. In addition, GBE reduced the E2 levels by stimulating the E2 metabolism and inhibiting E2 synthesis, which indicates that GBE can induce antiestrogenic activity via the depletion of E2. Furthermore, GBE might have similar action to selective arylhydrocarbon receptor modulators (SAhRMs), which induce antiestrogenic activity through cross-talk between the arylhydrocarbon receptor (AhR) and ER. In conclusion, GBE has a biphasic effect on estrogen, and can be considered as a potential alternative to HRT with chemopreventive effects on breast cancer. However, further studies on animals and humans will be required.


Substance P enhances cation permeability of neuronal cell lines.
Substance P stimulated the uptake of guanidinium in neuroblastoma X glioma hybrid cells and neuroblastoma cells but not in polyploid glioma cells. Guanidinium has previously been shown to pass the action potential Na+ channel in the two neuronal cell lines. Half-maximal stimulation was reached at 3 microM substance P and, with the hybrid cells, a saturation was seen above 10 microM. The analogue (D-Pro2,D-Trp7,9)-substance P, recently described as a substance P antagonist, caused a stimulation of guanidinium uptake comparable to that seen in the presence of substance P and did not inhibit the stimulation exerted by substance P. The pharmacological properties of the substance P-activated ion channel were investigated. Tubocurarine, phentolamine and propranolol blocked the substance P-stimulated guanidinium uptake with half-maximal inhibitory concentrations of 0.5, 5 and 50 microM. A similar characteristics has been found previously with the veratridine-activated Na+ channel in the cell lines investigated here. Peptides structurally related to substance P such as physalaemin and eledoisin, or others such as neurotensin, bradykinin, D-Ala2, Met5-enkephalinamide and ACTH(1-24) did not affect guanidinium uptake. In view of the high concentrations of substance P required for eliciting an effect in the cell lines, the involvement of specific receptors is questioned. A direct interaction of the peptide with the action potential Na+ channel is discussed.


Changes of plasma membrane properties in a human pre-T cell line undergoing apoptosis.
A variety of cellular functions are modulated by the physical properties of the cell membrane, and the modification of intracellular transfer, resulting from loss of membrane integrity, may contribute toward setting the cell onto the pathway of apoptosis. Apoptosis in lymphoid cells can be induced in different ways and biochemical modifications occur at an early phase of cell death, while the morphological features of apoptosis are evident later. We previously reported that DMSO is an efficient apoptosis-inducing factor in the human RPMI-8402 pre-T cell line. The aim of the present study was to verify the effect of DMSO on the plasma membrane fluidity, the intracellular calcium concentration and the phosphodiesterase activity in DMSO-induced apoptosis. Our results show a modification of membrane fluidity associated with an increase of intracellular Ca(2+) concentration. Moreover, we demonstrate that these modifications are related to a decrease in the phosphodiesterase (PDE) activity. The correlation between the proceedings of added DMSO and the induction of apoptosis will provide significant information regarding the first part of the apoptotic process.


[Postoperative peritonitis: intraperitoneal lavage with antibiotics (author's transl)].
Despite antibiotics, mortality in postoperative peritonitis has increased in the last 50 years. The main reasons are: modern medical technology and different types of patients. Operations are an unphysiologic intervention into the peritoneal cavity. The peritoneum is part of an immunologic defense system against bacterial growth and penetration into the peritoneal cavity. Circulatory and lymphatic vessels are in close contact. RES of the liver and spleen is stopped directly and indirectly by antibiotic drugs, and there is no pharmacodynamic direction after intraperitoneal injection. There is clinical improvement in mortality following lavage with antibiotics.


Strain and crystallographic identification of the helically concaved gap surfaces of chiral nanoparticles.
Identifying the three-dimensional (3D) crystal plane and strain-field distributions of nanocrystals is essential for optical, catalytic, and electronic applications. However, it remains a challenge to image concave surfaces of nanoparticles. Here, we develop a methodology for visualizing the 3D information of chiral gold nanoparticles ≈ 200 nm in size with concave gap structures by Bragg coherent X-ray diffraction imaging. The distribution of the high-Miller-index planes constituting the concave chiral gap is precisely determined. The highly strained region adjacent to the chiral gaps is resolved, which was correlated to the 432-symmetric morphology of the nanoparticles and its corresponding plasmonic properties are numerically predicted from the atomically defined structures. This approach can serve as a comprehensive characterization platform for visualizing the 3D crystallographic and strain distributions of nanoparticles with a few hundred nanometers, especially for applications where structural complexity and local heterogeneity are major determinants, as exemplified in plasmonics.


Epitope evolution in poliovirus maturation.
Eight monoclonal antibodies specific for native (N) poliovirus antigen all recognized empty capsids extracted from infected HeLa cells; only three of them recognized 14S particles. The facts point to the existence of two different epitopes N1 and N2, only one of which (N1) is present on 14S particles (these observations confirm and extend findings by EMINI et al). Another epitope of 14S particles is recognized by antibodies to heated (H) poliovirus antigen. Infected cell extract-catalyzed polymerization of 14S particles yielded mainly empty capsids carrying the N1 and N2, but no H epitopes.


Retail Sugar From One Zambian Community Does Not Meet Statutory Requirements for Vitamin A Fortification.
Industrial food fortification is a major strategy to improve dietary micronutrient intakes and prevent deficiencies. Zambia introduced mandatory sugar fortification with vitamin A, at a target of 10 mg/kg, in 1998. Representative surveys conducted since that time do not support marked improvement in vitamin A status. To describe vitamin A concentrations in retail sugar, as well as vendor practices, perceptions of fortified foods, and sugar use practices. We conducted a census of sugar vendors in one Zambian community, capturing information on vendors, available brands and packaging options, and storage conditions. We purchased all brands and package types of sugar available at each vendor. In a 15% subsample, we conducted semi-structured interviews with vendor-consumer pairs. We tested 50% of sugar samples at random for vitamin A using an iCheck portable fluorimeter. The distribution of vitamin A in sugar in market samples was highly skewed, with a median of 3.1 mg/kg (25th-75th percentiles: 1.8-5.5) and a range from 0.2 to 29.9 mg/kg. Only 11.3% of samples met the 10 mg/kg statutory requirement. Sugar was primarily repackaged and sold in small quantities, with rapid turnover of stocks. Perceptions of fortification by vendors and consumers were generally positive. Vitamin A in fortified sugar fell well below statutory requirements. Our data point to challenges at regional depot and/or poor adherence to fortification standards at the factory level. A renewed commitment to monitoring and enforcement will be required for Zambia to benefit from a food fortification strategy.


Back-reactions, short-circuits, leaks and other energy wasteful reactions in biological electron transfer: redox tuning to survive life in O(2).
The energy-converting redox enzymes perform productive reactions efficiently despite the involvement of high energy intermediates in their catalytic cycles. This is achieved by kinetic control: with forward reactions being faster than competing, energy-wasteful reactions. This requires appropriate cofactor spacing, driving forces and reorganizational energies. These features evolved in ancestral enzymes in a low O(2) environment. When O(2) appeared, energy-converting enzymes had to deal with its troublesome chemistry. Various protective mechanisms duly evolved that are not directly related to the enzymes' principal redox roles. These protective mechanisms involve fine-tuning of reduction potentials, switching of pathways and the use of short circuits, back-reactions and side-paths, all of which compromise efficiency. This energetic loss is worth it since it minimises damage from reactive derivatives of O(2) and thus gives the organism a better chance of survival. We examine photosynthetic reaction centres, bc(1) and b(6)f complexes from this view point. In particular, the evolution of the heterodimeric PSI from its homodimeric ancestors is explained as providing a protective back-reaction pathway. This "sacrifice-of-efficiency-for-protection" concept should be generally applicable to bioenergetic enzymes in aerobic environments.


Astaxanthin accumulation in Microcystis aeruginosa under different light quality.
The aim of this work was to uncover the astaxanthin biosynthesis mechanism in Microcystis aeruginosa under optimum light quality, and promote astaxanthin production using this alga. Among purple, blue and red light, only purple light promoted M. aeruginosa cell growth compared with white light, due to up-regulating expression of the genes related with DNA replication. An increase was detected in the photosynthetic rate under purple light, which should be caused by the raised carotenoid content and up-regulation of the genes associated with light reaction and carbon fixation. Compared with white light, purple light increased the levels of β-carotene, zeaxanthin and astaxanthin by up-regulating expression of the genes related with methylerythritol-4-phosphate pathway (MEP) and astaxanthin biosynthesis. For red and blue light, they did not impact or declined the content of astaxanthin and its precursors. Therefore, purple light promoted M. aeruginosa cell growth and astaxanthin production by up-regulating related gene expression.


Association of income and educational levels on initiation of oral anticoagulant therapy in patients with incident atrial fibrillation: A Finnish nationwide cohort study.
Socioeconomic disparities have been reported in the outcomes of patients with atrial fibrillation (AF). We assessed the hypothesis that AF patients with higher income or educational level are more frequently initiated with oral anticoagulant (OAC) therapy for stroke prevention. The nationwide registry-based Finnish AntiCoagulation in Atrial Fibrillation cohort covers all patients with AF from all levels of care in Finland. Patients were divided into income quartiles according to their highest annual income during 2004-2018 and into three categories based on educational attainment. The outcome was the first redeemed OAC prescription. We identified 239 222 patients (mean age 72.7 ± 13.2 years, 49.8% female) with incident AF during 2007-2018. Higher income was associated with higher OAC initiation rate: compared to the lowest income quartile the adjusted SHRs (95% CI) for OAC initiation were 1.09 (1.07-1.10), 1.13 (1.11-1.14) and 1.13 (1.12-1.15) in the second, third and fourth income quartiles, respectively. Patients in the highest educational category had a slightly lower OAC initiation rate than patients in the lowest educational category (adjusted SHR 0.92 [95% CI 0.90-0.93]). Income-related disparities were larger and education-related disparities only marginal among patients at high risk of ischemic stroke. The socioeconomic disparities in OAC initiation within 1-year follow-up decreased from 2007 to 2018. The adoption of direct OACs as the initial anticoagulant was faster among patients with higher income or educational levels. These findings highlight potential missed opportunities in stroke prevention, especially among AF patients with low income, whereas the education-related disparities in OAC initiation appear controversial.


COVID-19 pandemic impact on clinical outcomes of patients with obstructive pyelonephritis.
Obstructive pyelonephritis is a common urologic emergency that requires prompt decompression of the collecting system. The COVID-19 pandemic has changed patient flow and healthcare strategies at numerous emergency departments across Brazil with still unknown consequences for the population. This study sought to investigate the impact of the COVID-19 outbreak on clinical outcomes in patients with acute obstructive pyelonephritis at a tertiary academic center. After Institutional Review Board approval, a retrospective chart review of patients who required decompression of the collecting system due to acute obstructive pyelonephritis from June 2019 to July 2020 was conducted. Basic demographic information, pre-operative, and peri-operative data were recorded. Patients were assigned in "Pre-Covid" and "Post-Covid" groups based on the admission dates. A total of 63 patients were included, with 40 patients in the Pre-Covid group and 23 in the Post-Covid group. Patients from the Post-Covid group presented at the ER later after symptoms onset (7.8 vs. 4.3 days; p = 0.012), had higher rates of SIRS (57% vs. 25%; p = 0.012), perirenal abscesses (13% vs. 0%; p = 0.019), overall complications (p = 0.047) and presented longer hospital length of stay (7.6 vs. 3.8; p = 0.007). During the COVID-19 pandemic, patients with acute obstructive pyelonephritis presented later for evaluation at the ER, had higher disease severity and longer hospital length of stay when compared to the pre-COVID group of patients with the same pathology.


Localization and differential activity of P-glycoprotein in the bovine olfactory and nasal respiratory mucosae.
The purpose of this study was to demonstrate that P-glycoprotein (P-gp) is localized in the olfactory mucosa and is capable of limiting the nose-to-brain transport of substrates. Bovine olfactory and nasal respiratory mucosae were compared to both localize P-gp and to measure its activity within the epithelia. Immunolocalization was performed on the bovine olfactory and nasal respiratory mucosa using the C219 monoclonal antibody. Flux of etoposide, a substrate reported to be primarily effluxed by P-gp, across bovine olfactory and nasal respiratory mucosae was measured using Sweetana-Grass (Navicyte) vertical diffusion cells. Experiments were performed to evaluate the effect of directionality, donor concentration, and the presence of inhibitors. Dense staining was observed on the apical surface of the ciliated epithelial cells and within the submucosal lymphatics/vasculature and mucosal glands of the bovine olfactory and nasal respiratory mucosae. Staining in the nasal respiratory epithelium was weak and patchy when compared to that observed in the olfactory mucosa. The secretory transport (Js-m) kinetics of etoposide in the olfactory (Km = 260.5 microM, Vmax = 0.179 microM/cm(2) min) and nasal respiratory (Km = 46.9 microM, Vmax = 0.034 microM/cm(2) min) mucosae were observed to be saturable and concentration-dependent. The flux of etoposide in the submucosal-mucosal (Js-m) direction was significantly greater than the flux in the mucosal-submucosal (Jm-s) direction in both the olfactory and nasal respiratory mucosa. The efflux ratios (Js-m/Jm-s) of etoposide across the olfactory and the nasal respiratory mucosae were 2.02 and 2.10, respectively. In the presence of inhibitors such as 2,4-dinitrophenol (1 mM) and quinidine (1 mM), etoposide showed an increase in Jm-s and a decrease in Js-m. The etoposide efflux was unaffected in the presence of a specific multiresistance associated protein 1 (MRP1) inhibitor (MK571) and methotrexate, a substrate for BCRP and MRP1-4. P-gp was localized in the epithelial cells, nasal glands, and the vascular endothelium of both the bovine olfactory and nasal respiratory mucosae, and the expressed P-gp was capable of effluxing a substrate such as etoposide. The Km and Vmax of etoposide efflux were higher in the olfactory mucosa compared to the nasal respiratory mucosa, and the expression of P-gp seems to be greater in the olfactory epithelium compared to the nasal respiratory epithelium based on the staining density observed using immunohistochemistry.


Molecular mechanisms of odor-sensing. II. Studies of fractions from olfactory tissue scrapings capable of sensitizing artificial lipid membranes to action of odorants.
From the preparation obtained by ultrasonic disintegration of frog olfactory epithelium scraping, a fraction capable of sensitizing artificial phospholipid membranes to the action of some chemicals assumed to be odorants in frogs was isolated. In the presence of the active fraction, the membranes respond to the addition of camphor, linalool and musk ambrette by an increased permeability to Na+ and Ca2+. The main component of the active fraction is a nucleo-protein with molecular weight of no less than 100 000.


Development and characterization of IL-21-producing CD4+ T cells.
It has recently been shown that interleukin (IL)-21 is produced by Th17 cells, functions as an autocrine growth factor for Th17 cells, and plays critical roles in autoimmune diseases. In this study, we investigated the differentiation and characteristics of IL-21-producing CD4(+) T cells by intracellular staining. Unexpectedly, we found that under Th17-polarizing conditions, the majority of IL-21-producing CD4(+) T cells did not produce IL-17A and -17F. We also found that IL-6 and -21 potently induced the development of IL-21-producing CD4(+) T cells without the induction of IL-4, IFN-gamma, IL-17A, or IL-17F production. On the other hand, TGF-beta inhibited IL-6- and IL-21-induced development of IL-21-producing CD4(+) T cells. IL-2 enhanced the development of IL-21-producing CD4(+) T cells under Th17-polarizing conditions. Finally, IL-21-producing CD4(+) T cells exhibited a stable phenotype of IL-21 production in the presence of IL-6, but retained the potential to produce IL-4 under Th2-polarizing conditions and IL-17A under Th17-polarizing conditions. These results suggest that IL-21-producing CD4(+) T cells exhibit distinct characteristics from Th17 cells and develop preferentially in an IL-6-rich environment devoid of TGF-beta, and that IL-21 functions as an autocrine growth factor for IL-21-producing CD4(+) T cells.


Vancomycin-resistant enterococci (VRE) outbreak at a university hospital in Kitakyushu, Japan: case-control studies.
At a university hospital in Japan, a total of 15 patients (14 adults and 1 newborn baby) with vancomycinresistant enterococci (VRE) infection or colonization (inf/col) were identified via routine clinical examinations and two nonroutine examinations from January to April 2007. Two case-control studies were conducted to identify the factors related to VRE inf/col. In study 1, the patients with VRE inf/col from ward A (n = 8) were compared with all of the patients without VRE isolates in the same ward, i.e., the controls (n = 26). In study 2, all adult patients with VRE inf/col throughout the hospital (n = 14) were compared with controls randomly selected from among all patients without VRE isolates (n = 45). All the subject cases were found to be infected or colonized with Enterococcus faecium, vanB. All but two of the isolated strains were completely identical according to pulsed field gel electrophoresis. Univariate analysis in study 2 showed several factors, including the isolation of methicillin-resistant Staphylococcus aureus (MRSA) (odds ratio [OR], 8.6; 95% confidence interval [CI], 1.3-53.7) and the use of antibiotics other than anti-MRSA drugs (OR, 33.0; 95% CI, 1.8-587.6) to be risk factors for VRE inf/col. Multivariate logistic regression analysis in study 2 demonstrated associations with VRE inf/col in the use of an ultrasound nebulizer (OR, 5.9; 95% CI, 1.5-22.8) and extended bed rest (OR, 3.8; 95% CI, 1.02-24.5). Although severe infection with VRE did not occur, to avoid the spread of VRE in hospital wards, further staff education should be implemented in regard to the usual standard and contact precautions, and the appropriate selection of antibiotics.


Coronary Artery Disease Association With Arterial Calcifications on Routine Hand Radiographs.
Arterial calcifications in the lower extremity, chest, and cardiac vessels have been linked to coronary artery disease (CAD). However, the relation between arterial calcifications observed on routine hand and upper-extremity radiographs and atherosclerosis has not been determined. This study examined whether arterial calcifications found on hand radiographs are associated with CAD. A record review from a single institution identified 345 patients with both hand radiographs and CAD screening with cardiac stress testing or coronary angiography. Patients with chronic kidney disease, end-stage renal disease, or incomplete hand films were excluded. We reviewed x-rays for findings of arterial calcifications. Cardiac testing results were used to establish a baseline diagnosis of CAD. We made group comparisons and employed multivariable logistic regression to evaluate the association between upper-extremity calcification and CAD. A total of 210 patients met inclusion criteria: 155 with CAD and 55 without it. Mean age was 72 years, body mass index was 28.8, and 54% were male. Patients had comorbidities of hypertension (91%), hyperlipidemia (87%), diabetes (39%), cerebrovascular accident (9%), and a history of tobacco use (53%). Of 155 CAD patients, 67 had arterial calcifications on hand radiographs (43%), compared with 6 of 55 without it (11%). In a multivariable model controlling for sex, hyperlipidemia, and diabetes, the presence of arterial calcifications on hand plain films indicated a 6.2-fold increased odds of CAD. The current data demonstrate that arterial calcifications on hand radiographs are independently associated with CAD. This may represent an opportunity to the treating physician as a point of referral or investigation for underlying or occult CAD. Prevalence III.


Suppressing cyanobacterial dominance by UV-LED TiO2-photocatalysis in a drinking water reservoir: A mesocosm study.
Cyanobacteria and their toxic secondary metabolites present challenges for water treatment globally. In this study we have assessed TiO2 immobilized onto recycled foamed glass beads by a facile calcination method, combined in treatment units with 365 nm UV-LEDs. The treatment system was deployed in mesocosms within a eutrophic Brazilian drinking water reservoir. The treatment units were deployed for 7 days and suppressed cyanobacterial abundance by 85% while at the same time enhancing other water quality parameters; turbidity and transparency improved by 40 and 81% respectively. Genomic analysis of the microbiota in the treated mesocosms revealed that the composition of the cyanobacterial community was affected and the abundance of Bacteroidetes and Proteobacteria increased during cyanobacterial suppression. The effect of the treatment on zooplankton and other eukaryotes was also monitored. The abundance of zooplankton decreased while Chrysophyte and Alveolata loadings increased. The results of this proof-of-concept study demonstrate the potential for full-scale, in-reservoir application of advanced oxidation processes as complementary water treatment processes.


Increased sinusoidal pressure impairs liver endothelial mechanosensing, uncovering novel biomarkers of portal hypertension.
Portal hypertension (PH) is a frequent and severe clinical syndrome associated with chronic liver disease. Considering the mechanobiological effects of hydrostatic pressure and shear stress on endothelial cells, we hypothesised that PH might influence the phenotype of liver sinusoidal endothelial cells (LSECs) during disease progression. The aim of this study was to investigate the effects of increased hydrodynamic pressure on LSECs and to identify endothelial-derived biomarkers of PH. Primary LSECs were cultured under normal or increased hydrodynamic pressure within a pathophysiological range (1 vs. 12 mmHg) using a microfluidic liver-on-a-chip device. RNA sequencing was used to identify pressure-sensitive genes, which were validated in liver biopsies from two independent cohorts of patients with chronic liver disease with PH (n = 73) and participants without PH (n = 23). Biomarker discovery was performed in two additional independent cohorts of 104 patients with PH and 18 patients without PH. Transcriptomic analysis revealed marked deleterious effect of pathological pressure in LSECs and identified chromobox 7 (CBX7) as a key transcription factor diminished by pressure. Hepatic CBX7 downregulation was validated in patients with PH and significantly correlated with hepatic venous pressure gradient. MicroRNA 181a-5p was identified as pressure-induced upstream regulator of CBX7. Two downstream targets inhibited by CBX7, namely, E-cadherin (ECAD) and serine protease inhibitor Kazal-type 1 (SPINK1), were found increased in the bloodstream of patients with PH and were highly predictive of PH and clinically significant PH. We characterise the detrimental effects of increased hydrodynamic pressure on the sinusoidal endothelium, identify CBX7 as a pressure-sensitive transcription factor, and propose the combination of two of its reported products as biomarkers of PH. Increased pressure in the portal venous system that typically occurs during chronic liver disease (called portal hypertension) is one of the main drivers of related clinical complications, which are linked to a higher risk of death. In this study, we found that pathological pressure has a harmful effect on liver sinusoidal endothelial cells and identified CBX7 as a key protein involved in this process. CBX7 regulates the expression of E-cadherin and SPINK1, and consequently, measuring these proteins in the blood of patients with chronic liver disease allows the prediction of portal hypertension and clinically significant portal hypertension.


Corticotomy-assisted orthodontic enhancement by bone morphogenetic protein-2 administration.
To determine the possibility of synergistically enhancing orthodontic tooth movement (OTM) and bone formation in vivo by administering bone morphogenetic protein type 2 (BMP-2) on the tension side or in combination with corticotomy on the pressure side. The sample consisted of 56 Wistar rats that were subjected to experimental OTM for 32 days using a split-mouth design. The sample was divided into 4 groups: a control group, a corticotomy group, a BMP-2 group, and a corticotomy plus BMP-2 group. An OTM force of 10 cN was applied to each group. BMP-2 18 μL was administered locally on the tension side alone or in conjunction with corticotomy and then compared with the controls using fluorescence-based tartrate-resistant acid phosphatase staining for osteoclast counts, histologic bone resorption, and clinical OTM results. Corticotomy surgery increased the OTM rate (P < .05) by more than 20%. The injection of BMP-2 alone on the tension side did not induce significant changes in the degree of OTM compared with the vehicle-treated or control group (P > .05). When BMP-2 was combined with corticotomy on the tension and pressure sides (corticotomy plus BMP-2 group), respectively, nonsignificant OTM rates were observed (P > .05) compared with the controls; however, decreased osteoclast counts, bone resorption, and clinical results were observed in the corticotomy plus BMP-2 group. In contrast to reports published to date, the present preliminary study suggests that there are limits to OTM acceleration by bone formation on the tension side and agrees with the idea that there is a single continuous periodontal compartment in OTM, rather than a pressure side and a tension side.


Spinal cord injuries as a result of motorcycle accidents.
The orthopaedic and neurological lesions of 21 cases of spinal cord injuries as a result of motorcycle accidents are reviewed. The thoracic spine and spinal cord were the site of injury in 76% of cases. Eight-one per cent of the thoracic injuries showed complete neurological lesions. A mechanism of injury is postulated.


Adjuvant epirubicin followed by cyclophosphamide, methotrexate and fluorouracil (CMF) vs CMF in early breast cancer: results with over 7 years median follow-up from the randomised phase III NEAT/BR9601 trials.
The National Epirubicin Adjuvant Trial (NEAT) and BR9601 trials tested the benefit of epirubicin when added to cyclophosphamide, methotrexate and 5-fluorouracil (E-CMF) compared with standard CMF in adjuvant chemotherapy for women with early breast cancer. This report details longer follow-up with interesting additional time-dependent analyses. National Epirubicin Adjuvant Trial used epirubicin (E) 3-weekly for four cycles followed by classical (c) CMF for four cycles (E-CMF) compared with cCMF for six cycles. BR9601 used E 3-weekly for four cycles followed by CMF 3-weekly for four cycles, compared with CMF 3-weekly for eight cycles. In all, 2391 eligible patients were randomised and with a median 7.4-year follow-up, E-CMF confirmed a significant benefit over CMF in both relapse-free survival (RFS) (78% vs 71% 5 years RFS, respectively, hazard ratio (HR)=0.75 (95% CI: 0.65-0.86), P<0.0001) and overall survival (OS) (84% vs 78% 5 years OS, respectively, HR=0.76 (95% CI: 0.65-0.89), P=0.0007). Interaction of treatment effect and prognostic factors was demonstrated for duplication of chromosome 17 centromeric enumeration (Ch17CEP) as previously reported. Poor prognostic factors at diagnosis (ER and PR negative and HER2 positive) showed time-dependent annual hazard rates for RFS and OS. In univariate analysis, these factors demonstrated more favourable HRs for RFS after 5 years. Treatment effects also suggested a differential benefit for E-CMF within the first 5 years for poor prognosis tumours. Longer follow-up has confirmed E-CMF as significantly superior to CMF for all patients. Ch17CEP duplication was the only biomarker that demonstrated significant treatment interaction. Standard poor prognostic factors at diagnosis were time-dependent, and after 5 years disease-free, poor prognosis patients demonstrated favourable HRs for survival.


GHNN: Graph Harmonic Neural Networks for semi-supervised graph-level classification.
Graph classification aims to predict the property of the whole graph, which has attracted growing attention in the graph learning community. This problem has been extensively studied in the literature of both graph convolutional networks and graph kernels. Graph convolutional networks can learn effective node representations via message passing to mine graph topology in an implicit way, whereas graph kernels can explicitly utilize graph structural knowledge for classification. Due to the scarcity of labeled data in real-world applications, semi-supervised algorithms are anticipated for this problem. In this paper, we propose Graph Harmonic Neural Network (GHNN) which combines the advantages of both worlds to sufficiently leverage the unlabeled data, and thus overcomes label scarcity in semi-supervised scenarios. Specifically, our GHNN consists of a graph convolutional network (GCN) module and a graph kernel network (GKN) module that explore graph topology information from complementary perspectives. To fully leverage the unlabeled data, we develop a novel harmonic contrastive loss and a harmonic consistency loss to harmonize the training of two modules by giving priority to high-quality unlabeled data, thereby reconciling prediction consistency between both of them. In this manner, the two modules mutually enhance each other to sufficiently explore the graph topology of both labeled and unlabeled data. Extensive experiments on a variety of benchmarks demonstrate the effectiveness of our approach over competitive baselines.


Chemotherapy after palliative resection of colorectal cancer. Yorkshire Gastrointestinal Tumour Group.
Patients with residual disease after palliative resection of colorectal cancer were randomly allocated to receive methyl CCNU and 5-Fluorouracil or followed conventionally. There was a short term improvement in overall survival at 2 years significant at the 5 per cent level but ultimately all patients died. Chemotherapy did not significantly delay progression or prolong survival in patients with local residual disease. Although patients with more disseminated disease had a poorer prognosis than those with more limited disease, survival at 18 months was significantly prolonged (P less than 0.02 greater than 0.01) by chemotherapy.


Quantitation of hepatitis C virus RNA by third generation branched DNA-based signal amplification assay.
Quantitation of hepatitis C virus (HCV) RNA has become an important tool in different clinical settings and is used extensively for pretreatment evaluation of patients infected chronically with HCV. In this study, the performance characteristics of the third generation branched DNA-based signal amplification assay (bDNA 3.0) for HCV RNA quantitation were established. The new assay version showed an analytical specificity of 98%. Mean intra- and between-run imprecisions were 6.8 and 11.2%, respectively. The assay was linear over its entire dynamic range. Quantitation appeared to be unaffected by the genotypic variability of HCV. A comparison of bDNA 3.0 with the second generation bDNA assay calibrated against the international WHO HCV RNA standard, and the PCR-based Cobas Amplicor HCV Monitor 2.0 revealed a fairly good correlation among the assays. Twenty-nine and 11% of the paired quantitative results differed by more than log(10)0.5 (i.e. three-fold). All three assays after calibration against the WHO standard also yielded clinically comparable results with regard to the tailoring of interferon alpha/ribavirin treatment duration in patients infected by HCV genotypes 1, 4, and 5.


Open-label titration of apomorphine sublingual film in patients with Parkinson's disease and "OFF" episodes.
The efficacy and safety of apomorphine sublingual film (APL-130277; APL) for the on-demand treatment of "OFF" episodes associated with Parkinson's disease (PD) was demonstrated in a double-blind trial. Herein we describe the ability of patients to receive effective and tolerable APL dose titration during the open-label titration phase. Adult patients with levodopa-responsive PD and "OFF" episodes were enrolled. In practically defined "OFF," patients were observed for a FULL "ON" after their usual morning carbidopa/levodopa (CD/LD) dose and then after titration with APL following each increasing dose (10-35 mg). Antiemetic medication was administered for 3 days before initiation of titration and was continued throughout titration. Motor responses were evaluated predose and postdose using Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III score. Safety outcomes were evaluated. Among 141 patients who enrolled in the study and received APL during open-label titration, 109 (77.3%) achieved a FULL "ON" (66.1% at 10-20 mg) and 10 did not. Patients who successfully completed APL dose titration tended to be younger, had a longer mean time since PD diagnosis, and had lower levodopa requirements than those who discontinued during titration for any reason. Change in MDS-UPDRS Part III scores from predose to 30 min postdose after titration with the effective dose of APL (n = 109) was similar across all dose groups. In a post hoc analysis, the magnitude of motor response with APL was ~2-fold higher than with CD/LD 15 min postdose, and the observed peak response occurred earlier with APL than with the trend seen for CD/LD (45 vs 90 min, respectively). Overall, the most common (≥10%) treatment-emergent adverse events (TEAEs) during APL dose titration were nausea (20.6%), yawning (12.1%), dizziness (11.3%), and somnolence (11.3%). Twelve patients discontinued due to TEAEs during APL dose titration, most commonly (≥2%) because of dizziness (2.8%), nausea (2.1%), and somnolence (2.1%). Among eligible patients with PD and "OFF" episodes who had their APL dose successfully titrated to an effective and tolerable level, most were able to do so within the first 3 titrated doses but some required further dose escalations. The use of APL can provide benefit for the treatment of "OFF" episodes.


A Case Report of Successful Kidney Transplantation in a Patient With Chronic Myelogenous Leukemia (CML) Who Has Been in Remission for 15 Years on Imatinib.
For chronic myeloid leukemia (CML), a Philadelphia chromosome-positive myeloproliferative neoplasm, the introduction of tyrosine kinase inhibitors has transformed CML from a lethal disease into a manageable chronic disease with a close-to-normal life expectancy. Active malignancy is an absolute contraindication to kidney transplantation. However, it is controversial whether kidney transplantation can be safely performed in patients with a history of CML who are in remission. We describe the clinical course of a 64-year-old male patient with chronic kidney disease from diabetic nephropathy (DMN) who underwent living donor kidney transplantation. The patient was diagnosed with CML 15 years ago and promptly achieved cytogenetic and molecular biological remission after starting imatinib. After that, he continued imatinib treatment for 15 years and was in remission, but his chronic kidney disease from DMN gradually worsened. A preemptive living donor kidney transplant was performed in July 2020. Imatinib for CML was discontinued because the patient maintained deep molecular remission (DMR) of major molecular response for more than 15 years before kidney transplantation. After kidney transplantation, the transplanted kidney function remained good at approximate serum creatinine levels of 1.1 mg/dL without histopathologic rejection, and the 3 monthly BCR-ABL1 measurement results were negative and are in progress. Thus, he continues to maintain treatment-free remission status without imatinib for 26 months after renal transplantation. In conclusion, this result suggests that CML with long-lasting DMR on imatinib therapy can be considered an inactive malignancy and therefore a relative indication for kidney transplantation.


Primary banked scleral patch graft in the prevention of exposure of hydroxyapatite orbital implants.
The most frequently reported complication of hydroxyapatite orbital implantation is exposure of the implant, which may result in infection or extrusion of the implant. This study describes the use of banked sclera patch grafts to prevent implant exposure. A retrospective noncomparative interventional case series. The procedure was performed on 110 patients over a 2-year period. Hydroxyapatite implantation was performed either at the time of enucleation or as a secondary procedure to correct postenucleation socket syndrome. A banked scleral patch graft from the second eye of the same donor was placed over a scleral-wrapped hydroxyapatite implant at the time of operation. The case records were reviewed retrospectively. The primary outcome measure was the number of patients who developed exposure of their hydroxyapatite implant. The number of patients who had a postoperative conjunctival wound dehiscence was also recorded. No patients developed exposure of the implant. A significant percentage of patients developed conjunctival wound dehiscence (33%). Further surgery was not required in any of these cases, because the dehiscence spontaneously reconjunctivalized over the surface of the scleral patch graft. Insertion of a banked scleral patch graft at the time of hydroxyapatite orbital implantation is an effective means of preventing implant exposure, even in more complex cases. It thereby reduces the morbidity resulting from the procedure and obviates the need for further surgery when there is breakdown of the conjunctival wound postoperatively.


Lectin-Based Protein Microarray for the Glycan Analysis of Colorectal Cancer Biomarkers: The Insulin-Like Growth Factor System.
Lectin-based protein microarrays are used for glycoprofiling of various kinds of biological samples. Here we describe lectin-based microarray assay in the reverse-phase format where glycoprotein samples are spotted onto microarray slide and then are incubated with set of lectins. This configuration allows high-throughput screening of a large cohort of samples by a set of lectins without need of separation of glycans from glycoproteins. We applied the described method for glycan analysis of glycoprotein biomarkers of colorectal cancer associated with the insulin-like growth factor system.


Local anesthetics and pressure: a comparison of dibucaine binding to lipid monolayers and bilayers.
The binding of the local anesthetic dibucaine to monolayers composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine was studied with a Langmuir trough at pH 5.5 (22 degrees C, 0.1 M NaCl). At this pH value only the charged form of the local anesthetic exists in solution. Charged dibucaine was found to be surface active and to penetrate into the lipid monolayer, with the hydrophobic part of the molecule being accommodated between the fatty acyl chains of the lipid. The dibucaine intercalation could be quantitated by measuring the expansion of the film area, delta A, at constant surface pressure, pi. At a given surface pressure, delta A increased with increasing dibucaine in the buffer phase. On the other hand, keeping the dibucaine concentration constant, the area increase, delta A, was strongly dependent on the surface pressure. The area increase, delta A, was large at low surface pressure and decreased with increasing surface pressure. A plot of the relative change in surface area, delta A/A, versus the surface pressure yielded straight lines in the pressure range of 25-36 mN/m for five different concentrations. The delta A/A vs. pi isotherms intersected at pi = 39.5 +/- 1 mN/m with delta A = O, indicating that charged dibucaine apparently can no longer penetrate into the monolayer film. By making judicial assumptions about the area requirement of dibucaine the monolayer expansion curves could be transformed into true binding isotherms. Dibucaine binding isotherms were constructed for different monolayer pressures and were compared to a bilayer binding isotherm measured under similar conditions with ultraviolet spectroscopy. The best agreement between monolayer and bilayer binding data was obtained for a monolayer held at a pressure of 30.7 to 32.5 mN/m, which can thus be considered as the bilayer-monolayer equivalence pressure. It is further suggested from this analogy that the binding of dibucaine does not change the internal pressure in the bilayer phase, at least not in the concentration range of physiological interest (0-2 mM dibucaine) but induces a lateral expansion. At higher molar ratios of cationic dibucaine to lipid, chi b, in the monolayer (chi b greater than 0.20) the area increase is larger than would be expected from the molecular dimensions of dibucaine. This is probably due to charge repulsion effects, which at still higher molar ratios (chi b greater than 0.6) lead to a micellisation. The pressure dependence of the intercalation of cationic dibucaine into lipid membranes may also be of relevance for the phenomenon of pressure reversal in anesthesia.


Insulin receptor tyrosine kinase activity is reduced in monocytes from non-obese normoglycaemic insulin-resistant subjects.
Insulin sensitivity has been quantified by i.v. insulin tolerance test (0.1 U/kg of body weight) in 18 (11 male/7 female) non-obese (body mass index range 19-25 kg/m2) normoglycaemic subjects. We then compared the tyrosine kinase activity and internalization of insulin receptor in monocytes from the six most insulin-sensitive (group 1) and the six most insulin-resistant (group 3) subjects. Tyrosine kinase activity was measured on immunopurified receptors using 32P-ATP and poly-glutamic acid 4: tyrosine 1, sodium salt (poly-glu-tyr 4:1). Insulin internalization was studied by incubating cells with 1 nmol/l 125I-insulin and measuring total cell-bound and intracellular 125I-insulin by an acid dissociation procedure. Basal (in the absence of insulin) receptor kinase activity was similar in both groups. Maximal (in the presence of 100 nmol/l insulin) kinase activity was 41% lower in group 3 (13.8 +/- 3.6 fmoles 32P-ATP incorporated vs 23.3 +/- 4.0, p = 0.1). Delta increment of receptor kinase activity after insulin stimulation (calculated by subtracting basal from maximal activity) was significantly (p < 0.05) reduced in group 3 (21.3 +/- 3.8 vs 11.1 +/- 2.1) and significantly (p < 0.05) correlated to the in vivo insulin sensitivity. Both total cell-bound (0.70 +/- 0.09% of total radioactivity added vs 0.83 +/- 0.15) and intracellular (0.39 +/- 0.05 vs 0.44 +/- 0.09) 125I-insulin were similar in the two groups. These data suggest that in non-obese, normoglycaemic subjects a defective insulin receptor tyrosine kinase activity may contribute to the development of insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)


Atrial flutter and atrial fibrillation ablation - sequential or combined? A cost-benefit and risk analysis of primary prevention pulmonary vein ablation.
Recent studies have tested the hypothesis that preventive pulmonary vein isolation (PVI) at time of atrial flutter ablation in patients who have not had atrial fibrillation (AF) will reduce future incidence of AF. To model relative procedural costs, risks, and benefits of sequential versus combined ablation strategies. The decision model compares a sequential ablation strategy of atrial flutter ablation, followed by future PVI if necessary, with an initial combined flutter and preventive PVI ablation strategy. Assumptions are AF incidence 20% per year, PVI success rate 70%, PVI complication rate 4%, atrial flutter complication rate 1%, and costs $13,056 for PVI and $8,466 for atrial flutter ablation. The sequential ablation strategy is less expensive, at 1.4 vs 1.6 expected flutter ablation equivalents (FAE) ($11,852 vs $13,545) per patient, and entails less average risk, at 2% vs 4%. A combined ablation strategy is more expensive if the relative cost of PVI is more than 24.6% higher than atrial flutter ablation. A combined ablation strategy has higher total risk if PVI procedural risk is 24.6% more than atrial flutter ablation. Under base case assumptions of relative cost of PVI to flutter ablation 1.5 and relative risk 4, a sequential ablation approach has less total expected cost and less expected risk. There appears to be no compelling reason to adopt a combined ablation approach into standard practice. Nomograms are presented to allow the reader to assess which strategy is preferred according to local relative costs and risk.


Influence of mass transfer characteristics for DNAPL source depletion and contaminant flux in a highly characterized glaciofluvial aquifer.
The transfer of contaminant mass between the nonaqueous- and aqueous-phases is a process of central importance for the remediation of sites contaminated by dense nonaqueous-phase liquids (DNAPLs). This paper describes a comparison of the results obtained with various alternative DNAPL-aqueous-phase mass transfer models contained in the literature for predicting DNAPL source-zone depletion times in groundwater systems. These dissolution models were largely developed through laboratory column experiments. To gain insight into the implications of various representations of the local-scale kinetic as well as equilibrium DNAPL dissolution processes, aquifer heterogeneity and the complex architecture of a DNAPL source-zone, the aqueous-phase contaminant concentrations and mass fluxes arriving at a down-gradient compliance boundary are analyzed in a conditional stochastic framework. The hydrogeologic setting is a heterogeneous fluvial aquifer in Southwest Germany, referred to as the aquifer analog dataset, that was intensively characterized in three dimensions for hydrogeological parameters that include permeability, effective porosity, grain size, mineralogy and sorption coefficients. By embedding the various dissolution models into the compositional, multiphase flow model, CompFlow, the relative times predicted for complete depletion of a released DNAPL source due to natural dissolution are explored. Issues related to achieving environmental benefits through, for example, partial DNAPL-zone source removal via enhanced remedial technologies are also discussed. In this context, performance metrics in the form of peak aqueous-phase contaminant concentrations and mass fluxes arriving at a down-gradient compliance boundary are compared to each other. This is done for each of the alternative mass transfer models. A significant reduction in the fractional flux at a downstream location from the DNAPL source can be achieved by partial source-zone mass reduction; however, peak concentration levels at the same location remain much higher than the United States Environment Protection Agency (US-EPA) drinking water limits. Although groundwater quality was found to improve more rapidly for the equilibrium dissolution model, it is also shown that dissolution models that promote rapid DNAPL disappearance produce greater prediction uncertainty in the aqueous-phase flux reduction.


Numerical study and experimental validation of the size effect of smooth and mode I cracked semi-circular bend specimens.
The edge-cracked semi-circular bend (SCB) specimen subjected to three-point bending loading is used in many applications to measure the fracture behavior of quasi-brittle materials. The main objective of the present work was to study the effect of the crack length to SCB specimen radius ratio (a/R), span to specimen diameter ratio (S/D), and specimen size on its flexural and mode I crack growth behavior. The contour integral method was implemented using the 3-D finite element method to determine the mode I stress intensity factor. In addition, high-strength concrete specimens were experimentally studied to validate the numerical results. The results show that the maximum compression stress is not sensitive to the S/D value, while the tensile stress is very sensitive. The value of S/D is the main parameter controlling the crack driving force (i.e., the crack mouth opening displacement (CMOD) and the normalized stress intensity factor, YI). For the same S/D, the SCB specimen diameter value change has a marginal effect on CMOD and YI. The specimen with S/D = 0.8 showed that it is the most compatible specimen with three-point bending test conditions, regardless of the SCB specimen size. A good agreement between the numerical and experimental results was achieved.


Cytoplasmic c-Fos induced by the YXXQ-derived STAT3 signal requires the co-operative MEK/ERK signal for its nuclear translocation.
A STAT3 (signal transducer and activator of transcription 3)- and a MEK/Erk-mediated signal can be activated by cytokines, including IL-6 (interleukin-6), PDGF, and EGF. Recently, STAT3 and an ERK-signal were shown to co-operatively activate the c-fos gene. Activation of a truncated form of the IL-6 receptor subunit, gp130, that had only one YXXQ motif, induced both c-Fos and JunB in NIH3T3 cells through STAT3 without an apparent increase in the AP-1 (activator protein-1) activity. In contrast, concomitant stimulation of the STAT3 signal and a MEK/Erk-signal markedly increased AP-1 activity with enhanced c-Fos expression. Surprisingly, the c-Fos induced by the YXXQ-signal alone was localized to the cytoplasm, from which it translocated into the nucleus following TPA (12-O-tetradecanoyl-phorbol 13-acetate) treatment in a MEK/Erk-dependent manner. c-Fos that was expressed from a constitutive promoter localized to the nucleus and did not move into the cytoplasm in response to the YXXQ-signal. Rather, the YXXQ-signal was required during c-Fos production for it to be retained in the cytoplasm. Thus, the YXXQ-signal induces c-Fos expression through STAT3 and anchors the new c-Fos in the cytoplasm. In addition, the YXXQ-signal and an Erk signal co-operatively cause c-Fos activation in the nucleus.


Depression, posttraumatic stress, and alcohol misuse in young adult veterans: The transdiagnostic role of distress tolerance.
Alcohol misuse is common among young adult veterans, and is commonly associated with depression and posttraumatic stress disorder (PTSD). In fact, rates of comorbid depression, PTSD, and problem drinking are high in this population. Although distress tolerance, the capacity to experience and withstand negative psychological states, has been examined as a potential transdiagnostic factor that accounts for the development of mental health disorders, problem drinking, and the comorbidity between these presenting concerns, its role has not been evaluated in a veteran population. Young adult veterans were recruited for an online survey related to alcohol use. Participants (n=783) completed self-report measures of alcohol use, depression and PTSD symptoms, and distress tolerance. Mediation models were conducted to examine whether distress tolerance mediated the relationship between (1) probable PTSD, (2) probable depression, and (3) comorbid probable PTSD and depression with alcohol misuse. Moderated mediation models were conducted to examine gender as a moderator. Significant bivariate associations were observed among mental health symptoms, distress tolerance, and alcohol misuse. Distress tolerance significantly mediated the relationship between probable depression and PTSD (both alone and in combination) and alcohol misuse. Evidence of moderated mediation was present for probable PTSD and probable comorbid PTSD and depression, such that the indirect effect was stronger among males. These results suggest that distress tolerance may be a transdiagnostic factor explaining the comorbidity of depression and PTSD with alcohol misuse in young adult veterans. These findings may inform screening and intervention efforts with this high-risk population.


R848 or influenza virus can induce potent innate immune responses in the lungs of neonatal mice.
Innate immune responses are important to protect the neonatal lung, which becomes exposed to commensal and pathogenic microorganisms immediately after birth, at a time when both the lung and the adaptive immune system are still developing. How immune cells in the neonatal lung respond to innate immune stimuli, including toll-like receptor (TLR) agonists, or viruses, is currently unclear. To address this, adult and neonatal mice were intranasally administered with various innate immune stimuli, respiratory syncytial virus (RSV) or influenza virus and cytokine and chemokine levels were quantified. The neonatal lungs responded weakly to RSV and most stimuli but more strongly than adult mice to R848 and influenza virus, both of which activate TLR7 and the inflammasome. Notably, neonatal lungs also contained higher levels of cAMP, a secondary messenger produced following adenosine receptor signaling, than adult lungs and increased responsiveness to R848 was observed in adult mice when adenosine was coadministered. Our data suggest that the neonatal lung may respond preferentially to stimuli that coactivate TLR7 and the inflammasome and that these responses may be amplified by extracellular adenosine. Improved understanding of regulation of immune responses in the neonatal lung can inform the development of vaccine adjuvants for the young.


The metabolism of androstenedione and testosterone to C19 metabolites in normal breast, breast carcinoma and benign prostatic hypertrophy tissue.
In previous studies from our laboratory of the metabolism of androstenedione (A) and testosterone (T) in breast adipose and breast carcinoma tissue, the aromatization of these compounds, and their interconversion were demonstrated. The present study describes the conversion of androstenedione and testosterone to C19 metabolites in homogenates of normal breast tissue and breast carcinoma tissue and examines the C19 metabolites in homogenates of benign prostatic hypertrophy (BPH) tissue under similar conditions. Tissue homogenates were incubated for 90 min in Krebs-Ringer bicarbonate buffer (pH 7.4) with ATP (3 mM) and NADPH (2.4 mM) as co-factors. Following extraction with ethyl acetate, the metabolites were separated into neutral and phenolic fractions. Identification of specific products was made by thin layer and paper chromatography and recrystallization procedures. The formation of C19 metabolites was 10-fold greater in prostate than in breast tissue. Androsterone was the major product of androstenedione in both breast and prostate. The other 5 alpha-metabolites of androstenedione identified were dihydrotestosterone (DHT) and epiandrosterone (EPI). The 5 beta-metabolite, etiocholanolone (ET10), was identified in both breast and prostate following incubation with androstenedione. Using testosterone as substrate, dihydrotestosterone was the major product in normal breast and BPH. Etiocholanolone was detected in breast, but not in prostate following incubation with testosterone. Aromatization was demonstrated in all incubations with breast tissue, but not in prostate. The results indicate that androstenedione is actively metabolized by both breast and prostate to 5 alpha reduced metabolites. They also identify the formation of etiocholanolone in both tissues. Aromatization was demonstrated only in breast tissue.


Hypoadiponectinemia and aldosterone excess are associated with lack of blood pressure control in subjects with resistant hypertension.
Obesity, arterial stiffness and high aldosterone levels can interact to cause resistant hypertension (RHTN). Lower adiponectin (APN) levels may be significantly associated with hypertension. However, the importance of hypoadiponectinemia as a complicating factor in the lack of blood pressure (BP) control in individuals with RHTN has not been demonstrated. Ninety-six RHTN patients were classified into uncontrolled (UCRHTN, n = 44) and controlled (CRHTN, n = 52) subgroups. Their APN and aldosterone levels, office and ambulatory BP (ABPM) measurements, endothelium-dependent brachial artery responses (flow-mediated dilation (FMD)), left ventricular mass index (LVMI) and pulse wave velocity (PWV) were evaluated. The UCRHTN subgroup had increased aldosterone levels, as well as higher LVMI and PWV. In addition, lower APN levels and impaired FMD response were found in this subgroup. The brachial and ABPM pulse pressures were inversely associated with the APN levels (r = -0.45, P = 0.002; r = -0.33, P = 0.03, respectively), as were the aldosterone levels and the PWV (r = -0.38, P = 0.01; r = -0.36, P = 0.02, respectively) in UCRHTN patients. The PWV was only significantly influenced by the APN level in the UCRHTN subgroup in the multivariate regression analysis. None of the correlations mentioned above were observed in the CRHTN subgroup. Hypoadiponectinemia and high aldosterone levels may therefore be implicated in resistance to antihypertensive therapy related to arterial stiffness.


Proton-activated currents in chick spinal motoneurons.
Proton-activated currents were examined in patch-clamp recordings from embryonic chick motoneurons. Rapid application of protons evoked a large inward current that peaked and then decayed, presumably due to channel inactivation. A pH shift from 7.4 to 7.1 was sufficient to evoke detectable currents. The shift from pH 7.4 required for half-maximal current amplitude (EC50) was to pH 6.8. In single-channel recordings, activation was achieved within 6 ms at pH 7. The average channel open time was 1.4 ms; the closed-state time constants were 1.0 and 6.2 ms. At pH 6.5, the single-channel conductance was 22 pS, and the reversal potential was similar to the calculated Na+ equilibrium potential. Current amplitude declined by 49% following addition of Ni2+ and increased by 58% as Ca2+ was lowered from 2 to 0.1 mM. Inactivation time constants ranged from 90 to 200 ms as pH varied from 6 to 7; these values did not depend on membrane potential. The reactivation time constant was 22 s. Proton- and glutamate-activated currents summated. Thus, transient decreases in extracellular pH can evoke large inward currents that decay rapidly and reactivate slowly. These currents may occur under pathological conditions that affect extracellular pH.


Feeding habits and habitats preferences affecting mercury bioaccumulation in 37 subtropical fish species from Wujiang River, China.
The present study is the first to report the total mercury concentration of 37 fish species collected from Wujiang River, which is the largest branch on the southern bank of Yangtze River, China and proposed for hydropower development. Total mercury concentrations varied among the 37 subtropical species examined. We found higher mercury concentrations in carnivorous species demonstrating greater mercury bioaccumulation in species with more predatory feeding habits. There is no significant difference between fish grouped by habitat preference and feeding habit. However, carnivorous species preferring benthic positions had higher total mercury concentrations than others suggesting that mercury accumulation is related to the interaction of feeding habit and habitat preference. In our study, fish that are bottom living and feed on other fish or aquatic animals are more likely at high risk of mercury exposure. Additional mercury contamination and future impoundment may raise mercury concentration in fish in the Wujiang causing concern for human health and ecological impacts.


Influence of temperature on biomass production of clones of Atriplex halimus.
A very effective tool to combat desertification is revegetation. Promising species for this purpose are the evergreen shrubs of the genus Atriplex. The objective of the research was to study the growing responses of Atriplex halimus under different thermal regimes and to evaluate the biomass accumulation of selected clones. The test was carried out in four sites of Sardinia Island (Italy) characterized by different latitude, altitude and air temperature trends along the year. In every site, potted plants of five clones of A. halimus were compared for biomass production as measured by linear growth of plants (central axis and secondary shoots), as well as by dry weight of leaves, shoots and roots per plant. Correlations between sums of hour-degrees under or above the thresholds of critical air temperatures, comprised between 0 and 35 °C, and the plant growth indicators were analysed. Differences among the five clones, with regard to the influence of low temperatures on plant growth and on the biomass production were evaluated. Among five tested clones, GIO1 and SAN3 resulted more sensitive to low temperatures. Clones MAR1, PAL1 and FAN3 resulted less sensitive to low temperatures and in the site characterized by the lowest minimum temperatures also have shown greater adaptability and thus biomass growth in the observed period. The clone PAL1 showed a lower shoot/root biomass ratio as adaptation to cold temperature, and the clone FAN3, the opposite behaviour and a general preference to temperate thermal regimes.


Catabolism of benzene compounds by ascomycetous and basidiomycetous yeasts and yeastlike fungi. A literature review and an experimental approach.
A literature review is given on growth of yeasts on benzene compounds and on the catabolic pathways involved. Additionally, a yeast collection was screened for assimilation of phenol and 3-hydroxybenzoic acid. Fifteen ascomycetous and thirteen basidiomycetous yeast species were selected and were tested for growth on 84 benzene compounds. It appeared that 63 of these compounds supported growth of one or more yeast species. The black yeast Exophiala jeanselmei assimilated 54 of these compounds. The catechol branch of the 3-oxoadipate pathway and its hydroxyhydroquinone variant were involved in phenol and resorcinol catabolism of ascomycetes as well as of basidiomycetes. However, these two groups of yeasts showed characteristic differences in hydroxybenzoate catabolism. In the yeastlike fungus E. jeanselmei and in basidiomycetes of the genera Cryptococcus, Leucosporidium and Rhodotorula, the protocatechuate branch of the 3-oxoadipate pathway was induced by growth on 3- and 4-hydroxybenzoic acids. In three Trichosporon species and in all ascomycetous yeasts tested, 4-hydroxybenzoic acid was catabolyzed via protocatechuate and hydroxyhydroquinone. These yeasts were unable to cleave protocatechuate. 3-Hydroxybenzoic and 3-hydroxycinnamic acids were catabolized in ascomycetous yeasts via the gentisate pathway, but in basidiomycetes via protocatechuate. Incomplete oxidation of phenol, some chlorophenols, cresols and xylenols was observed in cultures of Candida parapsilosis growing on hydroquinone. Most compounds transformed by the growing culture were also converted by the phenol monooxygenase present in cell-free extracts of this yeast. They did not support growth. The relationship between the ability of ascomycetous yeasts to assimilate n-alkanes, amines and benzene compounds, and the presence of Coenzyme Q9 is discussed.


PROP-1 gene mutations in a 63-year-old woman presenting with osteoporosis and hyperlipidaemia.
PROP-1 gene mutations have been reported as a cause of combined pituitary hormone deficiency. Physical and hormonal phenotypes of affected individuals are variable. We report a 63-year-old female who presented with osteoporosis. She was short, did not enter puberty spontaneously and had primary amenorrhea. Biochemical evaluation revealed secondary hypothyroidism and mixed hyperlipidaemia, while dynamic testing of pituitary function was diagnostic of hypopituitarism. Bone density in the lumbar spine disclosed osteoporosis. DNA analysis showed that the patient was homozygote for the R73H mutation of the PROP-1 gene. The unfavourable long-term course of an untreated patient with PROP-1 gene mutation emphasizes the need for early aetiologic classification and proper management and follow-up of patients with short stature and/or disturbances of pubertal development.


Nasolacrimal intubation in transcanalicular endoscopic dacryoplasty: a long-term follow-up study.
Nowadays, transcanalicular endoscopic dacryoplasty represents the majority of lacrimal duct surgery procedures performed in adults in specialised centers. However, there are still hardly any data available regarding the intra- and postoperative care, particularly regarding the duration of silicone tube intubation (STI). Our aim was to evaluate the relation between tube duration and recurrence of symptoms in patients who underwent transcanalicular microdrill dacryoplasty (MDP) in a long-term setting. Medical records of 576 adult patients after MDP were retrospectively reviewed. A total of 256 eyes of 191 patients could be included. The median follow-up time was 7.83 [7.08; 9.25] years. In 57.0% of the cases there was still full resolution of symptoms at the time of the survey. The median duration of the STI was 6 [3.00; 6:00] months. When distinguishing between a tube duration < 3 months and ≥ 3 months there was a significant difference in the long-term success rate (< 3 months: 38%; ≥ 3 months: 61%; p = 0.011). In conclusion, an early removal of the STI (< 3 months) after transcanalicular MDP seems to be associated with a higher incidence of recurrence of symptoms. This should be considered in the intra- and postoperative care of patients following this minimally invasive first-step procedure.


Radiofrequency ablation-increased CXCL10 is associated with earlier recurrence of hepatocellular carcinoma by promoting stemness.
Radiofrequency ablation (RFA) represents a valuable choice in hepatocellular carcinoma (HCC); however, local recurrence of HCC is common after RFA. Here, 20 primary HCC patients treated by RFA were enrolled. Before (termed 0d) and after RFA treatment for 1 and 7 days (termed 1d and 7d, respectively), plasma and noncancerous tissue were collected. ELISA assay showed that plasma C-X-C motif chemokine 10 (CXCL10) was increased in ten patients (type I patients) but decreased in the other 10 patients (type II patients). The mean interval for HCC recurrence in type I patients was less than the mean interval in type II patients. Interestingly, a significant negative correlation between interval for HCC recurrence and fold change of plasma CXCL10 (1d/0d or 7d/0d) was identified, suggesting that RFA-induced CXCL10 is associated with earlier HCC recurrence. Immunofluorescence assay showed that the receptor of CXCL10, chemokine (C-X-C motif) receptor 3 (CXCR3), was significantly increased in type I, but not type II, patients after RFA. In vitro assay demonstrated that CXCL10 stimulus increased the rate of CD133(+) cancer stem cells (CSCs) in HepG2 cells by binding to CXCR3 and then inducing c-Myc expression. Many studies have reported that induction of CD133(+) CSCs contributes to HCC recurrence. Thus, CXCL10-increased CD133(+) CSCs by activating CXCR3/c-Myc pathway might accelerate HCC recurrence after RFA. These data might have potential implications for HCC therapy.


Magnetic resonance imaging of the neonatal piglet brain.
Appeal for the domestic pig as a preclinical model for neurodevelopmental research is increasing. One limitation, however, is lack of magnetic resonance imaging (MRI) methods for brain volume quantification in the neonatal piglet. The purpose of this study was to develop and validate MRI methods for estimating brain volume in piglets. The results showed that MRI and manual segmentation reliably estimated the changes in volume of different brain regions in 2- and 5-wk-old piglets. Substantial increases in the volumes of all brain regions examined were evident during the 3-wk period. MRI can provide accurate estimates of brain region volume during the neonatal period in piglets. A piglet model that can be used in longitudinal studies may be useful for investigating how experimental (e.g., nutrition, infection) factors affect brain growth and development. Anatomic MRI data (non-longitudinal) were acquired 2- and 5-wk-old piglets using a three--dimensional T1-weighted magnetization-prepared gradient echo (MPRAGE) sequence on a MAGNETOM Trio 3T imager. Manual segmentation was performed for volume estimates of total brain, cortical, diencephalon, brainstem, cerebellar, and -hippocampal regions. The MRI-based hippocampal volume estimates in 2- and 5-wk-old piglets were validated using histological techniques and the Cavalieri method.


[Characteristics of craniofacial identification using some comparative materials].
The peculiarities and techniques of craniofacial identification using lifetime video and X-ray photographs presented as comparative materials are examined.


The influence of Ca2+ ions on the difference absorption spectra of phosphorylase kinase.
A low iodide concentration causes a positive difference band in the 250-260 mm UV range. The effect of Ca2+ changes the direction of difference spectra. The concentration dependence is explained by multistage interaction. The addition of EDTA the solution restores the positive band.


Irradiance regulation of photosynthesis and respiration in modern marine microbialites built by benthic cyanobacteria in a tropical lagoon (New Caledonia).
Microbialites are organosedimentary deposits that have built up as a result of the growth and binding of detrital sediment by a benthic microbial community. This study focuses on microbialites built by monospecific populations of cyanobacteria in the south-west lagoon of New Caledonia, where they have been observed down to 20-25 m depth. The aim was to study their photosynthetic and respiratory responses to various light intensities. The Phormidium sp. TK1 microbialite was collected at 19 m depth and the P. crosbyanum (Tilden) microbialite was collected at 0.5 and 13 m depth. Phormidium sp. TK1 showed all the characteristic features of a low-light adapted species. The initial slope of the Photosynthesis versus Irradiance curve for this microbialite was close to the maximum quantum yield indicating an efficient light absorption and utilization at low light. The photosynthesis maximum was located 0.2-0.4 mm below the surface and did not shift with changing light intensity. Respiration rates were low and not enhanced by light; photoinhibition was observed at higher light intensities. In Phormidium crosbyanum (Tilden) microbialites, the photosynthesis maximum shifted downward to lower depths with increasing light, probably as a result of phototactic migration of cyanobacterial filaments, and light-enhanced respiration was observed at light intensities above light saturation. The photosynthetic para- meters measured in P. crosbyanum indicate that P. crosbyanum is capable of photo-acclimation at high light intensities. The gross productivity of the different microbialites was comparable to values measured in cyanobacterial stromatolites observed in other shallow environments. However, the microbialites studied here were characterized by a lower respiration / production ratio which indicates a higher growth efficiency.


Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma.
N-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT). Between April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy. With a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3-4 acute toxicities including bone marrow suppression (leukopenia: χ2 = 3.935, P = 0.047; anemia: χ2 = 9.760, P = 0.002; thrombocytopenia: χ2 = 8.821, P = 0.003), and both liver and renal dysfunction (χ2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups. IMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute toxicity rate.


Prevention of anaemia by early intervention with once weekly epoetin alfa during chemotherapy.
This study compared the effects of early intervention with standard use of epoetin alfa on haemoglobin (Hb) levels and transfusion requirements in cancer patients receiving chemotherapy. Patients with Hb>10 and < or= 12 g/dL were randomised 1:1 to epoetin alfa (40,000 IU, subcutaneously, once weekly), initiated within 7d of the start of the first on-study chemotherapy cycle (defined as early intervention) versus epoetin alfa when Hb <or= 10 g/dL (defined as standard therapy). Increases in Hb values were significantly higher with early intervention compared to standard therapy from week 6 to 10 (P <or= 0.05) and approached significance at week 15/16 (P=0.0531). Although the percentage of patients receiving blood transfusions was similar in both groups, the amount of blood transfused was almost twice as high in the standard epoetin alfa group (n.s.). Early intervention with epoetin alfa was well tolerated and overall survival did not differ significantly between groups. Initiation of epoetin alfa at the onset of chemotherapy and Hb<12 g/dL improves Hb levels significantly versus standard therapy.


Insomnia and depression.
It is clear that insomnia and depression are intimately related, which may suggest an overlapping neurobiology. Although much progress has been made toward understanding how these disorders relate to each other, the exact neurobiological mechanisms that link them remain elusive. Sleep changes in depression may be associated with abnormal neurotransmission, genetic polymorphisms, HPA overactivity, impaired plasticity, or most likely a combination of factors. It is therefore crucial that sleep assessments go beyond traditional polysomnography to include a more expanded set of objective measures in the hope that these will uncover the common neurobiology that is thought to underlie insomnia and depression.


Comparison of intravenous milrinone and dobutamine for congestive heart failure secondary to either ischemic or dilated cardiomyopathy.
Milrinone and dobutamine are positive inotropic agents with beneficial hemodynamic effects in patients with congestive heart failure. This study was undertaken to compare the effects of intravenous milrinone and dobutamine in patients with stable New York Heart Association class III or IV congestive heart failure and to test the hypothesis that intravenous milrinone is at least as beneficial as dobutamine in this setting. Seventy-nine patients were randomized to either dobutamine therapy at incremental doses of 2.5, 5, 7.5, 10, 12.5 and 15 micrograms/kg/min, or milrinone as a bolus of 50 or 75 micrograms/kg followed by an infusion of 0.5 to 1.0 micrograms/kg/min. Both agents significantly increased heart rate, cardiac index and stroke volume index and decreased pulmonary artery wedge pressure and systemic vascular resistance compared with baseline levels (p less than 0.01). During sustained infusion for 48 hours, no difference in hemodynamic effects was observed between the 2 drugs. Ventricular tachycardia occurred in 5 patients (3 taking milrinone, 2 taking dobutamine); 1 patient taking milrinone had ventricular fibrillation. Milrinone and dobutamine elicited similar beneficial hemodynamic results with relatively few adverse effects.


Affinity chromatography used in distinguishing alpha-fetoprotein in serum from patients with tumors of hepatic parenchyma and of germ cells.
We used affinity chromatography on concanavalin A Sepharose to study the serum alpha-fetoprotein of 10 patients with histologically proven germ-cell tumors and 12 patients with primary liver cancer. Less than 50% of the fetoprotein from germ-cell tumors bound to concanavalin A, as compared with more than 80% of the alpha-fetoprotein from primary liver cancers.


Disturbed gastrointestinal motility and decreased interstitial cells of Cajal in diabetic db/db mice.
Diabetes mellitus (DM) often causes gastrointestinal dysmotility. Interstitial cells of Cajal (ICC), which express c-kit receptor tyrosine kinase (KIT), are considered the pacemaker cells for gastrointestinal movement. The present study was designed to determine the role of ICC in the pathogenesis of gastroenteropathy in type 2 DM. We examined C57BL/KsJ-db/db mice as a model for type 2 DM. Gastrointestinal motility was evaluated by measuring gastric emptying, whole gut transit time, and isometric tension of the isolated small intestine. The area of KIT-positive cells in the gastrointestinal tract was examined by image analysis of fluorescent immunohistochemistry. The mRNA expression of KIT ligand, stem cell factor (SCF), in the gastrointestinal tract was quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR). Compared with 12-week-old db/+m control mice, diabetic db/db mice of the same age exhibited delayed gastric emptying, prolonged whole gut transit time, irregular frequency of isometric tension in the small intestine, smaller areas of KIT-positive cells in the antrum, small intestine, and colon, and lower mRNA expression levels of SCF in the small intestine and colon. We demonstrated disturbed gastrointestinal motility in db/db mice with reduced areas of ICC and expression of SCF. Our results suggest the involvement of ICC in the gastroenteropathy of type 2 DM.


Ileal adenomas in adenomatosis of the large intestine.
A report is given of 2 cases of adenomatosis of the colon in which adenomas of the ileum had been demonstrated. The clinical problems of these hitherto rarely observed neoplasias are discussed with reference to the available literature.


Reference Ranges and Development Patterns of Fetal Myocardial Function Using Speckle Tracking Echocardiography in Healthy Fetuses at 17 to 24 Weeks of Gestation.
The purposes of the study were to develop reference ranges and maturation patterns of fetal cardiac function parameters measured by speckle tracking echocardiography (STE) using multiple biometric variables at 17 to 24 weeks' gestation among Thai fetuses and to compare with other previous reports. The four-chamber view of the fetal heart in 79 healthy fetuses was suitably analyzed by STE to establish the best-fit regression model. The 95% reference intervals and Z-score equations of fetal cardiac function parameters were computed. The fractional area change of both ventricles, left ventricular (LV) end-diastolic and end-systolic volumes, LV stroke volume, LV cardiac output (CO), and LV CO per kilogram were all increased according to gestational age (GA) and five fetal biometric measurements. However, the global longitudinal strain, basal-apical length fractional shortening (BAL-FS), BAL annular free wall and septal wall FS, BAL free wall and septal wall annular plane systolic excursions, 24-segment transverse width FS, as well as LV ejection fraction were all independent of GA or other somatic characteristics. There were varying development patterns between fetal right and left ventricles of these cardiac function indices across the gestation period. Our study created Z-score and corresponding centile calculators, 5th and 95th centile reference tables, and corresponding graphs and determined the normal evolution across gestation using multiple somatic growth and age variables between 17 and 24 gestational weeks. These nomograms serve as an essential prerequisite for quantitatively evaluating fetal cardiac contractility and allow for precisely detecting early changes in the fetal heart function. · Most fetal cardiac function measurements were correlated with all the independent variables.. · Fetal ventricular function parameters have their own characteristic maturation changes.. · Racial variability may not occupy an important place for fetal myocardial function during these GA..


Babesia bovis (= argentina): changes in erythrophylic and associated proteins during acute infection of splenectomized and intact calves.
Saline eluates were prepared from sucrose-washed erythrocytes of cattle infected with B. bovis (= argentina). Fibrinogen, plasminogen and IgG2 were constituent proteins of the eluates and all three proteins increased in concentration during infection. The significance of the protein changes and their contribution to coagulation and fibrinolysis during infection are discussed.


[Dietary habits, dentoperiodontal health index and socioeconomic level in a group of school children].
The Authors evaluate social-economical level, dmft-DMFT, Pl.I., G.I. and alimentary habits of a school-children sample. The findings from the present study indicate that social-economic level influences both prevalence values of dental-periodontal pathology and alimentary habits.


Simultaneous detection in urine of cocaine and its main metabolites.
The simultaneous detection in urine of cocaine (CO), and the main biotransformation products, benzoylecgonine (BE) and ecgonine methyl ester (EME), is difficult due to their different physicochemical properties. The method presented involves a bonded silica solid-phase extraction procedure that allows mixed ionic and apolar interactions with the analyte. After extraction the compounds are derivatized sequentially with ethyliodide to obtain the BE ethyl ester derivative, and with N-methyl-N-trimethylsilyl trifluoroacetamide (MSTFA) to obtain the O-TMS derivatives. The derivatized compounds are then analysed by a capillary (methylphenylsilicone) gas chromatographic system equipped with a specific nitrogen-phosphorus detector. The method is suitable for the confirmation and quantitation of CO and its main metabolites in urine. BE levels in urine samples (n = 20) measured by the described method and by an immunological technique were in close agreement (r = 0.999).


Vascular closure system type of nonpenetrating arcuate-legged titanium clips for graft-artery and graft-graft anastomoses: review of our clinical experience.
To assess the durability of Vascular Closure System (VCS) clips for graft-artery and graft-graft anastomoses. The subjects were 100 consecutive patients, who had undergone vascular procedures in which VCS clip application was attempted for anastomoses. The operative indications were arteriosclerosis obliterans in 69 patients, aortic aneurysm in 26, and other disorders in 5. Large clips were used for both graft-artery and graft-graft anastomoses, and medium-sized clips were used for the smaller caliber femoral or popliteal arteries. Vascular Closure System clips could not be applied to anastomose the graft to the artery in 13 patients because the arterial wall was too thick or stiff. Anastomosis was accomplished without any problems in 80 patients, although suture-line bleeding occurred in 7 patients. This was ameliorated by an additional clip in four patients, but interrupted sutures were needed to seal the anastomosis in the other three patients. The 1-, 3-, and 5-year cumulative primary patency rates were 98.7%, 97.4%, and 87.7%, respectively. There were two graft failures and two anastomotic aneurysms. Vascular Closure System clips were useful to coapt a prosthetic graft to an artery unless the arterial wall was thicker than 2 mm or calcified. Thus, VCS clips could be durable enough for graft-artery anastomoses in the iliac or popliteal region.


Neuropsychiatric features of systemic lupus erythematosus.
Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious and well known complication of systemic lupus erythematosus that remains a significant source of morbidity and mortality. Fortunately, advances in neuroimaging techniques and cognitive testing have improved the diagnosis of this disease and allowed earlier and more successful therapeutic intervention. Further, the association of NPSLE with the anti-phospholipid syndrome, other autoantibodies and inflammatory cytokines have also provided clues to the diagnosis and pathophysiology. Treatment of NPSLE is largely symptom based with outcome based on appropriate diagnosis.


Successful long-term erythrocytapheresis therapy in a patient with symptomatic sickle-cell disease using an arterio-venous fistula.
The use of long-term automated erythrocytapheresis via an arterio-venous fistula for the prevention of recurrent ischaemic stroke in a child with sickle-cell disease (SCD) has not been described previously. We report the successful use of this technique in a 13-year-old boy. A procedure was performed every 36 +/- 6 days, transfusing six units of donor packed red blood cells (RBCs) and discarding 1318 +/- 174 mL of exchanged erythrocytes (Hct 60%). After transfusion of 85 units over 17 months, there is no evidence for iron-overload, red cell alloimmunization, transfusion-transmitted infections, or other complications. Until now, no cerebrovascular ischaemia has been observed.


Effects of chlorinated paraffins on liver weight, cytochrome P-450 concentration and microsomal enzyme activities in chick embryos.
Sublethal doses of three technical preparations of chlorinated paraffins (CPs) (Cereclor 42 (C22-26, 42% Cl w/w), Cereclor 50LV (C10-13, 49% Cl w/w) and Cereclor 70L (C10-13, 70% Cl w/w)) were injected into the yolks of hens' eggs after 4 days of incubation. The liver weight, the cytochrome P-450 concentration in the liver and the liver microsomal activity of aminopyrine N-demethylase (APND), aryl hydrocarbon (benzo[a]pyrene) hydroxylase (AHH) and 7-ethoxycoumarin O-deethylase (ECOD) were determined in chick embryos incubated for 20 days. The degree of chlorination and probably also the carbon chain length of the CPs were of importance for their effects. Cereclor 70L was the most potent in causing increases in liver weight, cytochrome P-450 concentration and APND activity. Cereclor 42 was the least potent in these respects, even causing reduced APND activity. A decrease in AHH activity occurred in chick embryos treated with Cereclor 50LV, and a reduction in ECOD activity was noted as a result of treatment with Cereclor 42 and Cereclor 50LV.


Primary Antibiotic Resistance to Helicobacter pylori Strains Isolated From Children in Northern Iran: A Single Center Study.
Initial resistance to antibiotics is the main reason for the failure of Helicobacter pylori (H. pylori) eradication in children. As we commonly face high antibiotic resistance rates in children, we aimed to determine the susceptibility of H. pylori to common antibiotics. In this cross-sectional in vitro study, 169 children younger than 14 years with clinical diagnosis of peptic ulcer underwent upper gastrointestinal endoscopy. Biopsy specimens from stomach and duodenum were cultured. In isolated colonies, tests of catalase, urease, and oxidase as well as gram staining were performed. After confirming the colonies as H. pylori, the antibiogram was obtained using disk diffusion method. Culture for H. pylori was positive in 12.3% of the specimens, urease test in 21.3%, serological test in 18.9% and stool antigen test was positive in 21.9%. We could show high specificity but moderate sensitivity of both histological and H. pylori stool antigen tests to detect H. pylori. The overall susceptibility to metronidazole was 42.9%, amoxicillin 95.2%, clarithromycin 85.7%, furazolidone 61.9%, azithromycin 81.0%, and tetracycline 76.2% with the highest resistance to metronidazole and the lowest to clarithromycin. In our region, there is high resistance of H. pylori to some antibiotics including metronidazole and furazolidone among affected children. To reduce the prevalence of this antibiotic resistance, more controlled use of antibiotics should be considered in children.


Excessive islet NO generation in type 2 diabetic GK rats coincides with abnormal hormone secretion and is counteracted by GLP-1.
A distinctive feature of type 2 diabetes is inability of insulin-secreting beta-cells to properly respond to elevated glucose eventually leading to beta-cell failure. We have hypothesized that an abnormally increased NO production in the pancreatic islets might be an important factor in the pathogenesis of beta-cell dysfunction. We show now that islets of type 2 spontaneous diabetes in GK rats display excessive NO generation associated with abnormal iNOS expression in insulin and glucagon cells, increased ncNOS activity, impaired glucose-stimulated insulin release, glucagon hypersecretion, and impaired glucose-induced glucagon suppression. Pharmacological blockade of islet NO production by the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) greatly improved hormone secretion from GK islets suggesting islet NOS activity being an important target to inactivate for amelioration of islet cell function. The incretin hormone GLP-1, which is used in clinical practice suppressed iNOS and ncNOS expression and activity with almost full restoration of insulin release and partial restoration of glucagon release. GLP-1 suppression of iNOS expression was reversed by PKA inhibition but unaffected by the proteasome inhibitor MG132. Injection of glucose plus GLP-1 in the diabetic rats showed that GLP-1 amplified the insulin response but induced a transient increase and then a poor depression of glucagon. The results suggest that abnormally increased NO production within islet cells is a significant player in the pathogenesis of type 2 diabetes being counteracted by GLP-1 through PKA-dependent, nonproteasomal mechanisms.


Ultrasound versus magnetic resonance arthrography in acetabular labral tear diagnostics: a prospective comparison in 20 dysplastic hips.
Acetabular labral tears are highly associated with hip dysplasia. Magnetic resonance arthrography (MR arthrography) is the expensive and time-consuming contemporary gold-standard method in the radiological assessment of acetabular labral tears. To assess the diagnostic ability of noninvasive ultrasound (US) examination compared to MR arthrography in diagnosing acetabular labral tears in dysplastic hip joints. The study compared US examination and MR arthrography diagnosis of labral tears in 20 consecutively referred dysplastic hip joints. The ability to diagnose acetabular labral tears upon US examination was calculated: sensitivity 44%, specificity 75%, positive predictive value 88%, and negative predictive value 25%. The ability of US examination in diagnosing acetabular labral tears is not yet good enough. The technique is still to be developed, and more experience, especially with the interpretation of US examinations, is needed.


Use of transparent vinyl polysiloxane in a minimally invasive approach for creating composite resin undercuts for partial removable dental prostheses.
A technique using a transparent vinyl polysiloxane material developed for use with light-polymerized composite resin and that does not require a lubricant is presented for creating composite resin undercuts for partial removable dental prosthesis clasps. With a surveyor, the undercut is waxed on the diagnostic cast according to the intended path of insertion. The transparent vinyl polysiloxane is used to fabricate a template for the undercut. The template is used intraorally to create the undercut in composite resin on the abutment tooth.