New prognostic markers in chronic lymphocytic leukemia.
The prognosis of patients with chronic lymphocytic leukemia (CLL) is extremely variable. Prognostication of patients with CLL has been classically based on clinical parameters. In the last few years, several biologic markers such as cytogenetics, IgVH mutations, CD38 and ZAP-70 expression in leukemic cells have shown to offer important prognostic information. However, before being incorporated into daily practice these markers require standardization and validation in prospective trials. Meanwhile, prognosis of patients with CLL should remain to be based on clinical stages and other easily obtainable clinical parameters. An important area of research is the identification of markers useful for predicting response to therapy. Among them, 17p- reflecting p53 abnormalities is particularly important. Also relevant is 11q- pointing out to ATM defects. The correlation of IgVH mutations, ZAP-70 and CD38 expression with response is unclear and needs further investigation. Finally, there is increasing evidence that response to therapy, particularly when all measurable disease is eradicated, is associated with longer survival.


Influence of autograft size on peripheral nerve regeneration in cats.
A combination of electrophysiological and histological techniques has been used to study the extent to which the size of an autograft affects myelinated axon regeneration in damaged cat peripheral nerves. The length of the graft and the match between the number of axons and Schwann cell basement membrane tubes in the graft and the repaired nerve were investigated. No difference was found in the success of regeneration through 10, 20 and 30 mm autografts. Changing the number of Schwann cell tubes available to regenerating myelinated axons also had no detectable effect on the success of regeneration.


Use of a new 8 French intracardiac echocardiographic catheter to guide device closure of atrial septal defects and patent foramen ovale in small children and adults: initial clinical experience.
Intracardiac echocardiography (ICE) has become an accepted imaging modality to guide device closure of atrial septal defect (ASD) and patent foramen ovale (PFO). The use of ICE to guide device closure of ASDs in small children (< 20 kg) has been very limited. We report on the use of a new, 8 Fr ICE catheter that possesses full color Doppler capabilities to guide device closure of ASDs in small children as well as to guide device closure of ASDs and PFOs in adult patients.


[Clinical symptoms of erosive and ulcerous lesions of gastroduodenal zone in patients with unstable ischemic heart disease and the significance of endoscopy in diagnosis].
We studied 103 patients with unstable ischemic heart disease and clinical signs of gastroduodenal injury. Among them 62 (60.2%) patients had moderate gastric dyspepsia and abdominal pain during first 1-5 days of hospitalization. In 17 (16.5%) cases these clinical symptoms were accompanied with symptoms of gastroduodenal hemorrhage. Twenty four patients (23.3%) with history of ulcer disease or chronic gastritis, were asymptomatic. In 96 (93.2%) patients endoscopy performed mainly on days 20-24 of hospital stay detected gastroduodenal erosions and ulcers: acute ulcers were found in 19.4, acute erosions - in 40.8, exacerbations of peptic ulcer - in 33.0% of patients. Clinical symptoms of gastroduodenal ulcers and erosions often did not reflect character, severity and dynamics of pathological process. Therefore gastro- duodenoscopy had decisive importance for diagnosis and assessment of effect of treatment. Endoscopy should be carried out with due consideration of concomitant coronary pathology.


Temperature effect on isometric tension is mediated by regulatory proteins tropomyosin and troponin in bovine myocardium.
The effect of temperature on isometric tension with and without the regulatory proteins tropomyosin and troponin was studied in bovine myocardium using a thin filament removal and reconstitution protocol. In control bovine myocardium, isometric tension increased linearly with temperature in the range 5-40 degrees C: isometric tension at 10 and 30 degrees C was 0.65 and 1.28 times that at 20 degrees C, respectively, with a Q10 of about 1.4. In actin filament-reconstituted myocardium without regulatory proteins, the temperature effect on isometric tension was less: isometric tension at 10 and 30 degrees C was 0.96 and 1.17 times that at 20 degrees C, respectively, with a Q10 of about 1.1. The temperature dependence of the apparent rate constants was studied using sinusoidal analysis. The temperature dependence of 2pi(b) (rate constant of delayed tension phase) did not vary significantly with the regulatory proteins under the standard activating condition (5 mM MgATP, 8 mM P(i), 200 mM ionic strength, pCa 4.66, pH 7.00). Q10 for 2pi(b) in control and actin filament-reconstituted myocardium was 3.8 and 4.0, respectively. There were two phases to the temperature dependence of 2pi(c) (rate constant of quick recovery). In control and thin filament-reconstituted myocardium, Q10 for 2pi(c) was approximately 5.5 in the low temperature range (< or = 25 degrees C) and 2.7 in the high temperature range (> or = 30 degrees C). In actin filament-reconstituted myocardium, Q10 for 2pi(c) was 8.5 in the low temperature range and 3.6 in the high temperature range. The above results demonstrate that regulatory proteins augment the temperature dependence of isometric tension, indicating that the regulatory proteins may modify the actomyosin interaction.


Gastrostomy feeding in infants and children on peritoneal dialysis.
The majority of infants and young children on peritoneal dialysis (PD) require enteral feeding to achieve their growth potential. We report our experience of gastrostomy feeding in 29 children on PD over 11 years. Fifteen children, median age 3.9 (0.5-13.3) years had a percutaneous gastrostomy (PEG) or Nissen fundoplication and gastrostomy (N and G) or open gastrostomy (OG) before starting PD (group1). Nine children, age 0.7 (0.5-12.4) years, had a N and G or OG (group 2) and 5, age 5.1 (1-15.1) years, a PEG (group 3) after PD catheter insertion/start of PD. In group 1 (257 months gastrostomy feeding with PD), there were 0.6 episodes of peritonitis/patient year. Nine PEGs were replaced electively after 27 (19-50) months, with bleeding from an embedded flange the only complication. One PEG replaced by a button ruptured the track, causing Candida peritonitis. In group 2 (130 months G and PD), there were 1.4 episodes of peritonitis/patient year. Two children developed paraoesophageal hernias, which were successfully repaired. Four children in group 3 developed peritonitis soon after PEG placement. Two transferred to haemodialysis, 1 remained on PD after treatment of Candida peritonitis and 1 subsequently died. Only 2 of the 17 children who have had renal transplants still need gastrostomy feeds. We recommend placement of a PEG or OG if an anti-reflux procedure is necessary prior to starting PD. Placement of a PEG while on PD is contraindicated, but an OG is a safe alternative procedure.


A unique collision of epithelioid hemangioendothelioma and bronchioloalveolar carcinoma in a 54-year-old Japanese woman.
We present a unique collision of epithelioid hemangioendothelioma and bronchioloalveolar carcinoma. A 54-year-old Japanese woman seen for a small nodular shadow on chest X-ray in December 1989 was found in chest computed tomography to have multiple small nodules in bilateral lung fields. At thoracotomy through a median sternotomy, 9 nodules from 0.3 cm to 1.2 cm in diameter detected were all resected. The pathological diagnosis was epithelioid hemangioendothelioma of the lung. A focus of bronchioloalveolar carcinoma 1.4 cm in diameter existed adjacent to the focus of epithelioid hemangioendothelioma in the lingular portion of the left lung. The initial surgical margin was not clear, and a complete lingulectomy was conducted through a left lateral thoracotomy. The patient is currently alive with no evidence of recurrence at 13 years after the first appearance.


A biochemically distinct sub-population of neurons in the human substantia gelatinosa. Study with G-6-PD histochemistry.
A method for localization of glucose-6-phosphate dehydrogenase (G-6-PD; D-glucose-6-phosphate: NADP+ oxidoreductase; E.C. 220.127.116.11) activity has been applied to human nervous tissue. Intensely staining cells, not definable by conventional histologic techniques, have been identified in the human spinal cord, with highest numbers present in the substantia gelatinosa of the sacral region. The cells have a neuron-like morphology and express neuronal-specific antigen but are heterogeneous in size and shape. They are not detectable in infant spinal cord, but stain heavily in adults. We propose that these cells are homologous to the G-6-PD-active dorsal medullary cells first noted by Sakharova et al. (1979) and together with the latter group, may comprise a hitherto unrecognized system of neurons in the human central nervous system.


Air pollution and lung cancer: diesel exhaust, coal combustion.
In 1946, when the causes of lung cancer were much less well understood than they are now, a meeting was held by the British Medical Research Council to review hypotheses to explain the remarkable increase in the death rates from lung cancer and to determine strategy. Stocks came away from the meeting to study the community aspects of air pollution, which he did by extending his series of correlation studies, Kennaway to conduct studies of carcinogens in the air, and Hill to carry out a study of smoking in relation to lung cancer. It is now known, of course, that cigarette smoking is by far the most important cause of lung cancer and that about a dozen occupational exposures are also established as causes of this disease. There has been continuing uncertainty about the role of general air pollution. During the past few years, this uncertainty has been compounded with anxiety that the increasing use of diesel-powered vehicles might lead to a deterioration in air quality and, with it, an increase in the incidence of lung cancer. The purpose of this paper is to assess the current role of air pollution as a factor in lung cancer and specifically the contribution of diesel exhaust emissions to the incidence of that disease.


Plasma levels of conjugated bile acids in newborns after a short period of parenteral nutrition.
Patients receiving parenteral nutrition (PN) frequently exhibit liver dysfunction. The authors previously reported that plant sterols of lipid emulsions added to the nutritional solution of newborns receiving PN accumulate in plasma and cell membranes and may contribute to the development of cholestasis. Conjugated bile acids (BA) have been shown to be useful markers of cholestasis. Plasma levels of several BA in newborns were quantified after administration of PN for less than 2 weeks. Plasma samples from 15 healthy control infants (CN), 22 patients who had received PN for 3-15 days (T1), and 9 patients scheduled to receive PN (T0) were analyzed. After a simple extraction procedure, plasma BA were analyzed by liquid chromatography-tandem mass spectrometry using a quantitative isotope dilution method. The concentrations of BA did not differ significantly between controls and patients before PN (CN vs T0), with the exception of glycocholic acid (GCA; 2.30 ± 2.60 µM vs 7.29 ± 5.39 µM, respectively). There was a significant difference in several BA between controls and patients after PN (2.30 ± 2.60 µM vs 7.61 ± 6.46 µM for GCA, respectively; 4.02 ± 3.49 µM vs 11.88 ± 11.05 µM for taurocholic acid [TCA], respectively; and 4.81 ± 3.49 µM vs 13.58 ± 12.22 µM for taurochenodeoxycholic + taurodeoxycholic + tauroursodeoxycholic acids [TCDCA+TDCA+TUDCA], respectively). In newborns receiving PN, a short period of PN is associated with an early increase of some conjugated BA. These results suggest that GCA, TCA, and TCDCA+TDCA+TUDCA levels could be used as early markers of PN-related cholestasis.


The pharmacological exploitation of cholesterol 7alpha-hydroxylase, the key enzyme in bile acid synthesis: from binding resins to chromatin remodelling to reduce plasma cholesterol.
Mammals dispose of cholesterol mainly through 7alpha-hydroxylated bile acids, and the enzyme catalyzing the 7alpha-hydroxylation, cholesterol 7alpha-hydroxylase (CYP7A1), has a deep impact on cholesterol homeostasis. In this review, we present the study of regulation of CYP7A1 as a good exemplification of the extraordinary contribution of molecular biology to the advancement of our understanding of metabolic pathways that has taken place in the last 2 decades. Since the cloning of the gene from different species, experimental evidence has accumulated, indicating that the enzyme is mainly regulated at the transcriptional level and that bile acids are the most important physiological inhibitors of CYP7A1 transcription. Multiple mechanisms are involved in the control of CYP7A1 transcription and a variety of transcription factors and nuclear receptors participate in sophisticated regulatory networks. A higher order of transcriptional regulation, stemming from the so-called histone code, also applies to CYP7A1, and recent findings clearly indicate that chromatin remodelling events have profound effects on its expression. CYP7A1 also acts as a sensor of signals coming from the gut, thus representing another line of defence against the toxic effects of bile acids and a downstream target of agents acting at the intestinal level. From the pharmacological point of view, bile acid binding resins were the first primitive approach targeting the negative feed-back regulation of CYP7A1 to reduce plasma cholesterol. In recent years, new drugs have been designed based on recent discoveries of the regulatory network, thus confirming the position of CYP7A1 as a focus for innovative pharmacological intervention.


Pretraining experience and structure of surgical training at a sub-Saharan African university.
The common goal of surgical training is to provide effective, well-rounded surgeons who are capable of providing a safe and competent service that is relevant to the society within which they work. In recent years, the surgical workforce crisis has gained greater attention as a component of the global human resources in health problems in low- and middle-income countries. The purpose of this study was to: (1) describe the models for specialist surgical training in Uganda; (2) evaluate the pretraining experience of surgical trainees; (3) explore training models in the United States and Canada and areas of possible further inquiry and intervention for capacity-building efforts in surgery and perioperative care. This was a cross-sectional descriptive study conducted at Makerere University, College of Health Sciences during 2011-2012. Participants were current and recently graduated surgical residents. Data were collected using a pretested structured questionnaire and were entered and analyzed using an excel Microsoft spread sheet. The Makerere University, College of Health Sciences Institutional Review Board approved the study. Of the 35 potential participants, 23 returned the questionnaires (65 %). Mean age of participants was 29 years with a male/female ratio of 3:1. All worked predominantly in general district hospitals. Pretraining procedures performed numbered 2,125 per participant, which is twice that done by their US and Canadian counterparts during their entire 5-year training period. A rich pretraining experience exists in East Africa. This should be taken advantage of to enhance surgical specialist training at the institution and regional level.


Long-term results after 27 years of surgical treatment of acute type a aortic dissection.
This study investigates the determinants of long-term outcome and modalities of late death after surgical treatment of acute type A dissection. Between 1974 and 2001, 315 consecutive patients were operated on for acute type A aortic dissection. Operative mortality was 22.9%. A series of 243 survivors of surgical treatment were followed up for as long as 27 years. Endpoints were death, cardiovascular reoperation, and neurologic events. Median follow-up was 4.5 years. Follow-up was 99.6% complete. Cumulative survival of discharged patients was 96.4% +/- 1.3%, 67.7% +/- 4.7%, and 39.4% +/- 12.0% at 1, 10, and 20 years, respectively. During follow-up, 47 patients died. Cause of death was cardiac failure in 7, hemorrhage due to rupture of the distal aorta in 7, stroke in 4, respiratory insufficiency in 4, sepsis in 3, malignancy in 2, and unknown in 20 patients. Multivariate analysis revealed advanced patient age and postoperative hemodialysis as perioperative indicators of late death (p < 0.05). Freedom from cardiovascular reoperation was 90.7% +/- 2.0% at 1 year, 60.9% +/- 5.1% at 10 years and 41.9% +/- 15.0% at 20 years. A total of 58 patients required 86 cardiovascular reoperations; aortic root or ascending aorta replacement was performed in 20, distal ascending aorta and arch replacement in 13, descending aorta replacement in 6, thoracoabdominal aorta replacement in 7, abdominal aorta replacement in 7, and miscellaneous reoperations in 6 patients. Multivariate analysis revealed male sex and left coronary artery dissection as significant determinants for late cardiovascular reintervention (p < 0.05). Cumulative incidence of stroke after 20 years was 3.8%. Acute type A dissection represents an emergency situation with acceptable long-term results for discharged survivors of surgical treatment.


Identification of different classes of superoxide dismutase in carnation petals.
Isoelectric focusing and nondenaturing two-dimensional electrophoresis, followed by an enzymatic characterization involving use of specific inhibitors were applied to identify the different forms of the superoxide dismutase (SOD) extracted from petals of cut carnation. Electrophoresis was carried out either with the crude extract or with fractions obtained after ion exchange chromatography of the extract. Three forms of the SOD were identified (Cu,Zn-SOD, Fe-SOD and Mn-SOD). They have close pI's (4.7 to 4.9) and most of them are composed of several isoforms.


Reproducible culture and differentiation of mouse embryonic stem cells using an automated microwell platform.
The use of embryonic stem cells (ESCs) and their progeny in high throughput drug discovery and regenerative medicine will require production at scale of well characterized cells at an appropriate level of purity. The adoption of automated bioprocessing techniques offers the possibility to overcome the lack of consistency and high failure rates seen with current manual protocols. To build the case for increased use of automation this work addresses the key question: "can an automated system match the quality of a highly skilled and experienced person working manually?" To answer this we first describe an integrated automation platform designed for the 'hands-free' culture and differentiation of ESCs in microwell formats. Next we outline a framework for the systematic investigation and optimization of key bioprocess variables for the rapid establishment of validatable Standard Operating Procedures (SOPs). Finally the experimental comparison between manual and automated bioprocessing is exemplified by expansion of the murine Oct-4-GiP ESC line over eight sequential passages with their subsequent directed differentiation into neural precursors. Our results show that ESCs can be effectively maintained and differentiated in a highly reproducible manner by the automated system described. Statistical analysis of the results for cell growth over single and multiple passages shows up to a 3-fold improvement in the consistency of cell growth kinetics with automated passaging. The quality of the cells produced was evaluated using a panel of biological markers including cell growth rate and viability, nutrient and metabolite profiles, changes in gene expression and immunocytochemistry. Automated processing of the ESCs had no measurable negative effect on either their pluripotency or their ability to differentiate into the three embryonic germ layers. Equally important is that over a 6-month period of culture without antibiotics in the medium, we have not had any cases of culture contamination. This study thus confirms the benefits of adopting automated bioprocess routes to produce cells for therapy and for use in basic discovery research.


Comparative Study of Lipid Content in Leptoclinus maculatus Postlarvae from Kongsfjord and Rjipfjord, Svalbard Archipelago.
A comparative study of lipid profile of the daubed shanny Leptoclinus maculatus postlarvae from fjords of different domains (arctic-boreal Kongsfjord and high-arctic Rjipfjord) of Svalbard Archipelago waters in summer was performed. A more efficient accumulation of lipids in the fishes from Kongsfjord compared to Rjipfjord due to triacylglycerols and wax esters was established. These differences may be related mainly to the trophic conditions of the habitat (species composition, abundance, and availability of food items). The higher level of cholesterol esters than wax esters at the L1 stage of development of the daubed shanny postlarvae compared to older fishes pointed to their active feeding mainly on phytoplankton. The differences in the content of certain classes of phospholipids may indicate adaptive changes at the level of biomembranes, contributing to the maintenance of cell homeostasis in response to abiotic environmental factors, and reflect their additional intake with food at the early stages of fish development.


Corrigendum: Gonadotropin Regulated Testicular RNA Helicase, Two Decades of Studies on Its Structure Function and Regulation From Its Discovery Opens a Window for Development of a Non-hormonal Oral Male Contraceptive.
[This corrects the article DOI: 10.3389/fendo.2019.00576.].


A primary study on rat fetal development and brain-derived neurotrophic factor levels under the control of electromagnetic fields.
In previous researches, electromagnetic fields have been shown to adversely affect the behavior and biology of humans and animals; however, body growth and brain-derived neurotrophic factor levels were not evaluated. The original investigation aimed to examine whether Electromagnetic Fields (EMF) exposure had adverse effects on spatial learning and motor function in rats and if physical activity could diminish the damaging effects of EMF exposure. In this study, we measured anthropometric measurements and brain-derived neurotrophic factor (BDNF) levels in pregnant rats' offspring to determine if Wi-Fi EMF also affected their growth. These data we report for the first time in this publication. Twenty Albino-Wistar pregnant rats were divided randomly into EMF and control (CON) groups, and after delivery, 12 male fetuses were randomly selected. For assessing the body growth change of offspring beginning at delivery, then at 21 postnatal days, and finally at 56 post-natal days, the crown-rump length of the body was assessed using a digital caliper. Examining BDNF factor levels, an Enzyme-linked immunosorbent assay ELISA kit was taken. Bodyweight was recorded by digital scale. Outcomes of the anthropometric measurements demonstrated that EMF blocked body growth in rats exposed to EMF. The results of the BDNF test illustrated that the BDNF in the EMF liter group was remarkably decreased compared to the CON group. The results indicate that EMF exposure could affect BDNF levels and harm body growth in pregnant rats' offspring. The results suggest that EMF exposure could affect BDNF levels and impair body growth in pregnant rats' offspring.


Implants of estradiol conjugated to bovine serum albumin in the male rat medial preoptic area promote copulatory behavior.
The expression of mating behavior in male rats is dependent on estrogen-responsive neurons in the medial preoptic area (MPO). Previous reports showed that mating is attenuated if the aromatization of testosterone to estradiol (E2) is blocked in the MPO and that mating is maintained by MPO E2 implants. However, the mechanisms by which E2 exerts its action are not fully understood. It had been thought that E2 acted exclusively by binding to nuclear estrogen receptors to exert it effects; however, recent reports suggest that E2 also binds to membrane-associated receptors activating downstream intracellular cascade responses. In this study, we aimed to determine if an action of E2 at the cell surface is sufficient to support mating behavior. Therefore, either vehicle, E2, or E2 conjugated to bovine serum albumin (BSA-E2: a complex of E2 and a large protein that will not cross the plasma membrane, thereby restricting the action of E2 to cell surface signaling) was chronically administered bilaterally to the MPO of castrated, dihydrotestosterone-treated male rats. Mating behavior was supported by MPO BSA-E2 implants, suggesting that E2 operates in the MPO via a cell surface mechanism to facilitate male rat mating behavior.


In vitro survival of MCF-7 breast cancer cells following combined treatment with ionizing radiation and mitoxantrone-mediated photodynamic therapy.
This study evaluated the effects of mitoxantrone (MX) as a sensitizer following combined treatment with ionizing radiation and photodynamic therapy in the MCF-7 human breast cancer cell line. Cells were incubated with MX at different concentrations for 90min and exposed to different fluence rates of non-coherent light and different dose rates of ionizing X-ray radiation in independent treatment groups. Additionally, the combined effects of chemotherapy, phototherapy, and radiotherapy were evaluated. The percent cell survival was investigated using the MTT assay. MX acted as both a photosensitizer and radiosensitizer. Furthermore, the use of 1μM MX in combination with PDT at 10J/Cm(2) and 4Gy of X-ray radiation strongly resulted in the death of cancer cells and reduced the percentage of viable cancer cells to 2.4±1.15. Our data demonstrated that the adverse effects of MX in combination with radiotherapy were partially abated, without a reduction in the efficacy of treatment. This new therapeutic avenue for breast cancer therapy merits further investigation using in vivo models for application in humans.


Increment thresholds in normal and binocularly deprived cats.
Increment thresholds on a white background were determined for normal and binocularly deprived (BD) cats over a wide luminance range. Threshold vs intensity curves had a slope of unity for both groups but the increment threshold (delta I/I) for normal cats was 0.09 while increment threshold for BD cats was 0.60. Absolute threshold was reliably better in normal cats. the deficit of BD cats is considered a potential result of their abnormal cortical physiology and/or abnormal lateral geniculate physiology.


Cost-sharing strategies combining targeted public subsidies with private-sector delivery achieve high bednet coverage and reduced malaria transmission in Kilombero Valley, southern Tanzania.
Cost-sharing schemes incorporating modest targeted subsidies have promoted insecticide-treated nets (ITNs) for malaria prevention in the Kilombero Valley, southern Tanzania, since 1996. Here we evaluate resulting changes in bednet coverage and malaria transmission. Bednets were sold through local agents at fixed prices representing a 34% subsidy relative to full delivery cost. A further targeted subsidy of 15% was provided to vulnerable groups through discount vouchers delivered through antenatal clinics and regular immunizations. Continuous entomological surveys (2,376 trap nights) were conducted from October 2001 to September 2003 in 25 randomly-selected population clusters of a demographic surveillance system which monitored net coverage. Mean net usage of 75% (11,982/16,086) across all age groups was achieved but now-obsolete technologies available at the time resulted in low insecticide treatment rates. Malaria transmission remained intense but was substantially reduced: Compared with an exceptionally high historical mean EIR of 1481, even non-users of nets were protected (EIR [fold reduction] = 349 infectious bites per person per year [x4]), while the average resident (244 [x6]), users of typical nets (210 [x7]) and users of insecticidal nets (105 [x14]) enjoyed increasing benefits. Despite low net treatment levels, community-level protection was equivalent to the personal protection of an ITN. Greater gains for net users and non-users are predicted if more expensive long-lasting ITN technologies can be similarly promoted with correspondingly augmented subsidies. Cost sharing strategies represent an important option for national programmes lacking adequate financing to fully subsidize comprehensive ITN coverage.


Role of central 5-HT2 receptors in mediating head bobs and body shakes in the rabbit.
Systemic administration of the 5-HT(2A/2C) agonist DOI [(1(2,5-dimethoxy-4-iodophenyl)-2-aminopropane)hydrochloride] in rabbits elicits head bobs and body shakes, which are mediated by 5-HT(2A) and 5-HT(2C) receptors, respectively. This study was designed to determine whether the receptors mediating these behaviors are primarily located in the brain or in the periphery. Systemic administration of the peripheral 5-HT(2A/2C) antagonist xylamidine 30 min before systemic DOI challenge attenuated DOI-elicited body shakes by 50% without an effect on head bobs, suggesting a central origin for head bobs and a partial peripheral and a partial central origin for body shakes. Central administration of DOI into the lateral ventricle (ICV) elicited head bobs but not body shakes, demonstrating that the receptors mediating head bobs are centrally located. Pretreatment with ICV xylamidine blocked head bobs elicited by ICV DOI, indicating that the lack of inhibition, when systemically administered, is due to xylamidine's failure to reach central receptors. ICV pretreatment with the 5-HT(2A) receptor antagonist ketanserin inhibited ICV DOI-elicited head bobs establishing that 5-HT(2A) receptors activation elicits head bobs. In conclusion, 5-HT(2A) receptors mediating head movements are located in the brain whereas 5-HT(2C) receptors mediating the body movements appear to be located at different central sites as well as in the periphery.


c-Abl kinase regulates neutrophil extracellular trap formation and lung injury in abdominal sepsis.
Sepsis is associated with exaggerated neutrophil responses although mechanisms remain elusive. The aim of this study was to investigate the role of c-Abelson (c-Abl) kinase in neutrophil extracellular trap (NET) formation and inflammation in septic lung injury. Abdominal sepsis was induced by cecal ligation and puncture (CLP). NETs were detected by electron microscopy in the lung and by confocal microscopy in vitro. Plasma levels of DNA-histone complexes, interleukin-6 (IL-6) and CXC chemokines were quantified. CLP-induced enhanced phosphorylation of c-Abl kinase in circulating neutrophils. Administration of the c-Abl kinase inhibitor GZD824 not only abolished activation of c-Abl kinase in neutrophils but also reduced NET formation in the lung and plasma levels of DNA-histone complexes in CLP mice. Moreover, inhibition of c-Abl kinase decreased CLP-induced lung edema and injury. Administration of GDZ824 reduced CLP-induced increases in the number of alveolar neutrophils. Inhibition of c-Abl kinase also markedly attenuated levels of CXC chemokines in the lung and plasma as well as IL-6 levels in the plasma of septic animals. Taken together, this study demonstrates that c-Abl kinase is a potent regulator of NET formation and we conclude that c-Abl kinase might be a useful target to ameliorate lung damage in abdominal sepsis.


Preschoolers' use of reflective properties: identification of reflections on partially transparent surfaces.
This exploratory study extended past studies of children's ability to reference the mirror as a tool in locating the source of reflected images to preschoolers' ability to use the affordances of a transparency. Thirty-six children (3.5 to 5 years old) were shown nonreflected lights and lights reflected on a partially transparent, glassy surface. Children did not spontaneously locate the source of the reflected image. However, they were able to verbally discriminate reflected from nonreflected images following training. These findings indicate that, although preschoolers may not spontaneously use transparencies as a perceptual tool, the ability to distinguish visual differences of reflected from nonreflected images on transparencies is likely within preschool children's developmental capacity.


Low-dose doxapram for treatment of apnoea following early weaning in very low birthweight infants: a randomized, double-blind study.
The effects of low-dose doxapram (0.5 mg kg(-1)h(-1)) in combination with caffeine were evaluated on apnoea frequency following weaning from mechanical ventilation, and on blood pressure, in very low birthweight (BW) premature infants. Twenty-nine infants with BW < or=1250 g, gestational age at birth (GA) <34 weeks and postnatal age <5 d, who required minimal respiratory support, were included. Following randomization, they received a loading dose of caffeine citrate and a continuous infusion of doxapram (doxapram, n=14) or placebo (n=15) was started. They were extubated 8 h after starting the infusion, which was continued for 5 d. During this period, weaning was well tolerated in both groups, apnoeas occurred less frequently and there was a greater increase in systolic blood pressure in infants treated with doxapram than in controls. Plasma doxapram levels were also higher than expected. It is therefore suggested that doxapram, even at low doses, should not be used during the first few days of life. Careful monitoring of blood pressure is required if doxapram is used later.


Tuberculous peritonitis with infracarinal mass and elevated CA-125 in a 13-year-old girl.
A 13-year-old girl with weight loss and ascites was admitted with suspicion of a malignant disease. Abdominal magnetic resonance imaging indicated extensive peritonitis and showed no evidence of a solid tumor. As a new imaging observation, thoracic computed tomography showed a lymphoma-like infracarinal mass and further enlarged lymph nodes in the pathway of draining lymph ducts. A tuberculin skin test and an interferon-gamma blood test were positive, and the tumor marker CA-125 was elevated. Histology of a peritoneal biopsy showed infectious granulomas with central necrosis, and Mycobacterium tuberculosis could be cultured, leading to the diagnosis of a tuberculous peritonitis. The girl received multi-drug anti-tuberculous treatment and subsequently recovered. At follow-up the peritonitis and the infracarinal mass had vanished. In conclusion, tuberculous peritonitis is a rare but relevant differential diagnosis in peritonitis of unknown origin. Its diagnosis is facilitated by imaging, by tuberculosis skin and blood tests, and by clinical interpretation.


Within-lake dispersal of the prosobranch snails, Viviparus ater and Potamopyrgus jenkinsi.
The gastropod species Viviparus ater and Potamopyrgus jenkinsi have both colonized Lake Zürich relatively recently. If it is assumed that they have dispersed in the Lake starting from one location, a model of random diffusion is insufficient to explain their present distribution in Lake Zürich. It is suggested that both species were dispersed by humans. In P. jenkinsi, passive dispersal by birds, fish or on floating algae may also have occurred. To estimate the rate of within-lake dispersal, life tables were constructed and the diffusivity estimated for the two species. Per capita population growth rates were calculated to be 0.00337/d for V. ater and 0.0159/d for P. jenkinsi. Diffusivity was close to 1 m2/d in both species.


Multicomponent phenol hydroxylase-catalysed formation of hydroxyindoles and dyestuffs from indole and its derivatives.
To establish multicomponent phenol hydroxylases (mPHs) as novel biocatalysts for producing dyestuffs and hydroxyindoles such as 7-hydroxyindole (7-HI) from indole and its derivatives. We have isolated Pseudomonas sp. KL33, which possesses a phenol degradation pathway similar to that found in Pseudomonas sp. CF600. Pseudomonas sp. KL28 is a strain that can grow on n-alkylphenols as a carbon and energy source. Escherichia coli strains expressing mPH from strain KL28 (mPH(KL28)) and strain KL33 (mPH(KL33)) catalysed the formation of indigo and 7-HI, respectively, from indole. In addition, both mPHs catalysed the production of dyestuffs and hydroxyindoles from indole derivatives. The mPH(KL28) has proved to be one of the most versatile biocatalysts that can accommodate a wide range of indole derivatives for catalysing the formation of dyestuffs. The present work provides a new approach in producing various dyestuffs and hydroxyindoles from indole and its derivatives by mPHs. These results indicate that mPHs may serve as potential agents for organic syntheses as well as bioremediation.


Development of a 2-hydroxyglutarate production system by Corynebacterium glutamicum.
2-Oxoglutarate (2-OG) is a tricarboxylate cycle intermediate that can be biologically converted into several industrially important compounds. However, studies on the fermentative production of compounds synthesized from 2-OG, but not via glutamate (defined as 2-OG derivatives), have been limited. Herein, a system that can efficiently produce 2-hydroxyglutarate (2-HG), a 2-OG derivative biosynthesized by the hgdH-encoded NADH-dependent 2-HG dehydrogenase of Acidaminococcus fermentans, was developed as a model using Corynebacterium glutamicum. First, the D3 strain, which lacked the two NADH-consuming enzymes, lactate dehydrogenase and malate dehydrogenase, as well as isocitrate lyase, was constructed as a starting strain. Next, the growth conditions that induced the accumulation of 2-OG were investigated, and it was found that the biotin- and nitrogen-limited (B/N-limited) aerobic growth conditions were suitable for this purpose. Finally, the hgdH gene of A. fermentans became overexpressed in the D3 strain by inserting it into the intergenic regions with the strong constitutive promoter of the tuf gene of C. glutamicum; the engineered strain was cultured under the B/N-limited aerobic growth conditions. The engineered strain produced 80.1 mM 2-HG with a yield of 0.390 mol/mol glucose, which are the highest titer and yield reported thus far, to the best of our knowledge. Furthermore, reverse genetics showed that the produced 2-HG was partially exported via the YggB protein (NCgl1221 protein, a mechanosensitive channel) known as an exporter for glutamate under the conditions used herein. KEY POINTS: • An efficient 2-HG production system was developed with Corynebacterium glutamicum. • Biotin- and nitrogen-limited aerobic growth conditions induced 2-OG production. • Produced 2-HG was partially excreted via the glutamate exporter, YggB.


Work-related stress risk assessment in Italy: a methodological proposal adapted to regulatory guidelines.
Work-related stress is one of the major causes of occupational ill health. In line with the regulatory framework on occupational health and safety (OSH), adequate models for assessing and managing risk need to be identified so as to minimize the impact of this stress not only on workers' health, but also on productivity. After close analysis of the Italian and European reference regulatory framework and work-related stress assessment and management models used in some European countries, we adopted the UK Health and Safety Executive's (HSE) Management Standards (MS) approach, adapting it to the Italian context in order to provide a suitable methodological proposal for Italy. We have developed a work-related stress risk assessment strategy, meeting regulatory requirements, now available on a specific web platform that includes software, tutorials, and other tools to assist companies in their assessments. This methodological proposal is new on the Italian work-related stress risk assessment scene. Besides providing an evaluation approach using scientifically validated instruments, it ensures the active participation of occupational health professionals in each company. The assessment tools provided enable companies not only to comply with the law, but also to contribute to a database for monitoring and assessment and give access to a reserved area for data analysis and comparisons.


Functional 5-HT receptors in human occipital artery.
5-HT receptors were studied in human occipital arteries, obtained from patients during neurosurgery. We detected mRNA for the following receptors (incidence): 5-HT(1B) (14/18), 5-HT(1D) (15/18), 5-HT(2A) (16/18), 5-HT(2B) (8/8), 5-HT(4(a)) (13/18), 5-HT(4(b)) (5/18), 5-HT(4(g)) (7/18), 5-HT(4(i)) (1/18), 5-HT(7(a/b)) (10/18) and 5-HT(7(d)) (12/18). 5-HT contracted and relaxed arterial rings at low (-logEC(50) M=7.0) and high (-logEC(50) M=4.2) concentrations, respectively. 5-HT-evoked contractions were antagonized partially by both 5-HT(1B)-selective SB224289 (200 nM) and 5-HT(2A)-selective ketanserin (1 microM) but not by 5-HT(1D)-selective BRL15572 (500 nM) or prazosin (1 microM). Sumatriptan caused contractions (-logEC(50) M=6.8, intrinsic activity with respect to 5-HT=0.3). Sumatriptan-evoked contractions were antagonized by SB224289 with high potency (pK(B)=9.4) but not by BRL15572. 5-HT-induced relaxations were resistant to blockade by 5-HT(1B)-selective SB224289 (1 microM), 5-HT(1D)-selective BRL15572, 5-HT(2B)-selective SB204741 (1 microM), 5-HT(4)-selective GR113808 (100 nM) and 5-HT(7)-selective SB269970 (1 microM), and a combination of SB204741 and SB269970, inconsistent with an involvement of 5-HT(1B), 5-HT(1D), 5-HT(2B), 5-HT(4) and 5-HT(7) receptors. Triton X-100 treatment of the arteries abolished acetylcholine-induced relaxations of rings precontracted by prostaglandin F(2alpha), but a reduction of the relaxant effects of 5-HT did not reach significance. Nitro-L-arginine (1 mM) reduced 5-HT-induced relaxations, suggesting a contribution of nitric oxide released from endothelial cells. Ketanserin (1 microM) prevented the relaxant effects of 5-HT. We conclude that 5-HT contracts human occipital artery through 5-HT(1B) receptors at low concentrations and through 5-HT(2A) receptors at high concentrations. Sumatriptan contracts mostly through 5-HT(1B) receptors. These results are consistent with the 5-HT(1B) and 5-HT(2A) mRNA data. 5-HT-induced relaxation is mediated, in part, through ketanserin-sensitive receptors, but 5-HT(1B), 5-HT(1D), 5-HT(2B), 5-HT(4) and 5-HT(7) receptors appear not to be involved.


Cyclic AMP in the rat cerebral cortex after stimulation of the locus coeruleus: decrease by antidepressant drugs.
The study concerned the effect of repeated treatment with antidepressant drugs on the elevation of cyclic AMP levels in the rat cerebral cortex following electrical stimulation of the locus coeruleus. Some of the tricyclic and tetracyclic antidepressant drugs inhibited the cyclic AMP response. Desmethylimipramine was the most potent (effective when given 5 mg/kg/day for 2 weeks). Imipramine and nomifensine (daily dose 10 mg/kg for 2 weeks) produced slight decreases, while iprindol and clomipramine were ineffective. After 6 weeks of treatment (daily 10 mg/kg) iprindol, clomipramine and mianserin were without effect. The cyclic AMP response was suppressed by higher doses of the latter two drugs (2 weeks, 20 mg/kg/day). These results indicate that tricyclic and tetracyclic antidepressant drugs are able to decrease cerebral noradrenergic neurotransmission of locus coeruleus neurons, as far as this is mediated by cyclic AMP. It is not clear, however, whether such modification is related to the therapeutic action of antidepressant drugs.


Primary adenosquamous carcinoma of the stomach: experience of 11 cases and its clinical analysis.
1) During the last 10 years, 11 cases of primary adenosquamous carcinoma of the stomach were operated on. 2) Histologically, the specimens from the stomach showed adenocarcinoma with squamous differentiation in all the cases. 3) All the patients but 1 were males and their average age was 61.2 years. 4) The duration of illness prior to treatment was relatively long period of time and the chief complaints in over half of the patients were abdominal pain. 5) Eight cases showed metastases at the time of operation. Metastasis to the regional lymph nodes was observed in 8 cases and the squamous element was present in 5 of these cases. 6) There was no operative death. Followup study was made in 9 cases. Only 2 are still alive and the remaining 7 died of recurrence. The length of survival averaged 10.7 months.


Low density lipoprotein metabolism in type IV and type V hyperlipoproteinemia.
Low density lipoproteins (LDL) are thought to arise largely from degradation of triglyceride-rich very-low-density lipoproteins (VLDL). LDL kinetics in patients with Type IV and Type V hyperlipoproteinmia were studied and compared with normal subjects. LDL labeled in the protein moiety with 125I was used as a tracer. There was no significant difference in LDL turnover between the three groups, suggesting that a catabolic defect in VLDL degradation to LDL may exist in both Type IV and Type V hyperlipoproteinemia.


Control of gene expression in the P2-related temperate coliphages. V. The use of sequence analysis of 186 Vir mutants to indicate presumptive repressor binding sites.
The prophage of coliphage 186 produces a repressor protein that is required for maintenance of lysogeny and that renders lysogenic cells immune to superinfection by 186. The repressor is likely to be a DNA-binding protein that prevents transcription of the 186 early-lytic genes from promoter pR. To identify the binding site of the repressor, we have isolated virulent mutants that are able to form plaques in the presence of repressor and determined their DNA sequences around pR. The mutants all have mutations in an inverted repeat within pR, and we predict that this repeat is the primary binding site of the repressor. Many of the mutants have second mutations near pR, which allow them to form plaques in the presence of higher concentrations of repressor. The sequences containing these "secondary" mutations show no homology with the putative repressor-binding site, and the role of these mutations in virulence is not clear.


Magnetic resonance imaging of less common pancreatic malignancies and pancreatic tumors with malignant potential.
Pancreatic tumors are an increasingly common finding in abdominal imaging. Various kinds of pathologies of the pancreas are well known, but it often remains difficult to classify the lesions radiologically in respect of type and grade of malignancy. Magnetic resonance imaging (MRI) is the method of choice for the evaluation of pancreatic pathologies due to its superior soft tissue contrast. In this article we present a selection of less common malignant and potentially malignant pancreatic neoplasms with their characteristic appearance on established MRI sequences with and without contrast enhancement.


Use of Mendelian randomization to evaluate the effect of atrial fibrillation on cardiovascular diseases and cardiac death.
Several observational studies indicated that atrial fibrillation might aggravate other cardiovascular diseases apart from ischaemic stroke. However, it remains to be determined whether these associations reveal independent causation. Using Mendelian randomization (MR), we systematically investigated how genetically predicted atrial fibrillation affected other cardiovascular diseases and cardiac death. Summary-level data for atrial fibrillation and other cardiovascular diseases were obtained from public genome-wide association study data. The random inverse-variance weighted method was treated as the primary analysis. Sensitivity analyses (including weighted median, MR-Egger, and multivariable MR methods) were also performed. Atrial fibrillation was significantly associated with higher risks of heart failure [odds ratio (OR): 1.24; 95% confidence interval (CI): 1.19-1.28; P < 0.001], ischaemic stroke (OR: 1.21; 95% CI: 1.17-1.25; P < 0.001), transient ischaemic attack (OR: 1.10; 95% CI: 1.05-1.15; P < 0.001), peripheral artery diseases (OR: 1.09; 95% CI: 1.03-1.15; P = 0.002), cardiac death (OR: 1.08; 95% CI: 1.02-1.15; P = 0.008), and hypertension (OR: 1.06; 95% CI: 1.01-1.11; P = 0.010), without effects on coronary heart disease or pulmonary embolism. Associations for heart failure and ischaemic stroke remained robust to the sensitivity analyses. MR-Egger method (P > 0.05) and funnel plot yielded no indication of directional pleiotropy. The leave-one-out analysis suggested that the causal associations were not driven by individual single nucleotide polymorphism. This comprehensive MR analysis verified the causal associations between atrial fibrillation and high risks of heart failure, ischaemic stroke, transient ischaemic attack, peripheral artery diseases, cardiac death, and hypertension. Interventions to reduce cardiovascular diseases beyond ischaemic stroke are warranted in patients with atrial fibrillation.


Oridonin inhibits SASP by blocking p38 and NF-κB pathways in senescent cells.
Cellular senescence is a state of irreversible cell growth arrest that functions as a biological defense mechanism against severe DNA damage. Senescent cells with DNA damage produce pro-inflammatory cytokines, such as IL-6 and IL-8, and this phenomenon is called the senescence-associated secretory phenotype (SASP). SASP factors have been implicated in various disorders, including cancer. We performed a screening assay and identified oridonin as a candidate SASP inhibitor. Oridonin is an active diterpenoid that is isolated from Isodon plants and has been reported to exhibit anti-inflammatory, antibacterial, antioxidant, and antitumor activities. It reduced the secretion of IL-6 and IL-8 in senescent cells at the protein and mRNA levels. Oridonin also inhibited p65 subunit of NF-κB activity. However, oridonin did not affect SA β-gal activity and enhanced the expression of p21. The expression and phosphorylation of p38 were down-regulated by oridonin. The p38 inhibitor SB203580 inhibited the secretion of IL-8, slightly inhibited the secretion of IL-6, and did not affect NF-κB activity. Therefore, the NF-κB and p38 pathways may contribute to the inhibition of SASP by oridonin. Oridonin has potential as a therapeutic agent for SASP-related diseases.


Effect of fasting on diarrhoea in collagenous colitis.
Diarrhoea in collagenous colitis has been considered as secretory though the pathophysiology has been studied thoroughly in only a few patients. The result of fasting is one way to distinguish between secretory and osmotic diarrhoea. Our aim was to investigate the effect of fasting on diarrhoea in collagenous colitis. Fourteen patients with collagenous colitis were admitted to the hospital for investigation. All were female. Five of these did not have diarrhoea during admission and were excluded. Stools were examined for weight, electrolytes, pH, fat and osmolality during a period on a normal diet and during fasting. During the fasting period the faecal weight was significantly reduced from median 757 (440-3,198) to 191 (22- 2,197) g. The faecal sodium concentration was also reduced, though not significantly, during fasting from median 65 (29-85) to 45 (19-88) mmol/l. The osmotic gaps varied according to the method of calculation applied. The data indicate that the cause of the diarrhoea in collagenous colitis could be multifactorial. In some patients an osmotic factor dominates and in others a secretory factor, while in some patients a combination of both seems to exist.


Gastric variceal bleeding from segmentary idiopathic splenic vein stenosis with left-sided portal hypertension: An unappreciated complication of pregnancy.
Segmentary idiopathic splenic vein stenosis is a very rare condition. We report a unique case of acute gastric variceal bleeding in a 31-year-old pregnant woman with left-sided portal hypertension from segmentary idiopathic splenic vein stenosis. Hemorrhage was controlled by endoscopic acrylate glue injection and urgent cesarean section allowed successful delivery. The patient declined subsequent intervention and has been on beta-blockers with no bleeding recurrence since then. This condition, its pathophysiological implications and management are discussed.


Tissue signals imprint ILC2 identity with anticipatory function.
Group 2 innate lymphoid cells (ILC2s) are distributed systemically and produce type 2 cytokines in response to a variety of stimuli, including the epithelial cytokines interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP). Transcriptional profiling of ILC2s from different tissues, however, grouped ILC2s according to their tissue of origin, even in the setting of combined IL-25-, IL-33-receptor-, and TSLP-receptor-deficiency. Single-cell profiling confirmed a tissue-organizing transcriptome and identified ILC2 subsets expressing distinct activating receptors, including the major subset of skin ILC2s, which were activated preferentially by IL-18. Tissue ILC2 subsets were unaltered in number and expression in germ-free mice, suggesting that endogenous, tissue-derived signals drive the maturation of ILC2 subsets by controlling expression of distinct patterns of activating receptors, thus anticipating tissue-specific perturbations occurring later in life.


Protective effect of s-allyl cysteine and s-propyl cysteine on acetaminophen-induced hepatotoxicity in mice.
In vivo protective effects of s-allyl cysteine (SAC) and s-propyl cysteine (SPC) against acetaminophen-induced hepatotoxicity in Balb/cA mice were studied. SAC and SPC at 1g/L were added into drinking water for four weeks and followed by acetaminophen treatment. Acetaminophen treatment significantly depleted glutathione content, increased oxidation stress and elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities (P < 0.05); however, the intake of SAC or SPC significantly alleviated glutathione depletion and the elevation of ALT and AST, enhanced glutathione peroxidase activity, and lowered malondialdehyde formation (P < 0.05). Plasma levels of C-reactive protein (CRP), von Willebrand factor (vWF), IL-6, IL-10 and TNF-alpha were significantly increased by acetaminophen treatment (P < 0.05); and SAC or SPC intake significantly suppressed acetaminophen-induced elevation of CRP, vWF and the three cytokines (P < 0.05). Acetaminophen treatment also significantly increased plasminogen activator inhibitor-1 (PAI-1) activity and plasma fibrinogen level, and decreased antithrombin III (AT-III) and protein C activities (P < 0.05). SAC or SPC intake alleviated AT-III and protein C reduction (P < 0.05); but did not affect PAI-1 activity and plasma fibrinogen level (P > 0.05). These data suggest that SAC and SPC are potential multiple-protective agents against acetaminophen-induced hepatotoxicity.


Current status and future directions in the management of chronic hepatitis C.
Hepatitis C virus (HCV) is endemic worldwide, and it causes cirrhosis and other complications that often lead to death; nevertheless, our knowledge of the disease and its mechanisms is limited. HCV is most common in underdeveloped nations, including many in Africa and Asia. The virus is usually transmitted by parenteral routes, but sexual, perinatal, and other types of transfer have been known to occur. Approximately 80% of individuals who contract hepatitis C develop a chronic infection, and very few are able to spontaneously clear the virus. Because hepatitis C is asymptomatic in the majority of patients, the presence of HCV RNA in the serum is the best diagnostic tool. Although serious complications from hepatitis C may not occur for 20 years, 1/5 of chronic patients eventually develop life - threatening cirrhosis. More research is needed on the different therapy options for the disease, and many factors, most importantly the genotype of the virus, must be taken into account before beginning any treatment. As there is no vaccine against HCV at present, the most effective and recommended therapy is pegylated-interferon-α-2a plus ribavirin. While interferon is marginally effective as a monotherapy, both adding the moiety and combining it with ribavirin have been shown to dramatically increase its potency. While there are numerous alternative and complementary medicines available for patients with hepatitis C, their efficacy is questionable. Currently, research is being done to investigate other possible treatments for hepatitis C, and progress is being made to develop a vaccine against HCV, despite the many challenges the virus presents. Until such a vaccination is available, prevention and control methods are important in containing and impeding the spread of the virus and mitigating its deleterious effects on the health of people and communities worldwide.


PCDD/Fs emissions from secondary copper production synergistically controlled by fabric filters and desulfurization.
The effects of fabric filters and desulfurization systems during secondary copper smelting on polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) concentrations, emission coefficients, and profiles were studied in an oxygen-rich smelting furnace and an anode furnace. In the anode furnace, the toxic equivalent (TEQ) concentration ranges were 0.106-1.04 ng World Health Organization (WHO)-TEQ/m3 at the fabric filters inlet and 0.027-0.17 ng WHO-TEQ/m3 at the outlet. For the oxygen-rich smelting furnace, the TEQ concentration ranges were 1.21-1.93 and 0.010-0.019 ng WHO-TEQ/m3 at the desulfurization system inlet and outlet, respectively. The TEQs in the outlet stack gases of the desulfurization system from the anode furnace were 0.0041-0.016 ng WHO-TEQ/m3. It is likely that PCDD/Fs that were taken away from the stack gases were adsorbed by the fly ash and gypsum. Solid residues were the dominant release routes for PCDD/Fs. PCDD/Fs congener and homologue profiles of stack gases from different smelting stages were similar. The contributions of more chlorinated homologues from the anode furnace decreased observably after the stack gases passed through the fabric filters. However, the desulfurization process did not greatly change the PCDD/Fs homologue profiles. Overall, both the fabric filters and desulfurization systems showed excellent removal efficiencies for PCDD/Fs in the stack gases, which reduced the TEQ emissions to well below the 0.5 ng WHO-TEQ/m3 to achieve standard discharge.


Anchoring Cu Nanoclusters on Melamine-Formaldehyde Microspheres: A New Strategy for Triggering Aggregation-Induced Emission toward Specific Enzyme-Free Methyl Parathion Sensing.
Methyl parathion (MP) residues have aroused extensive attention on account of their significant threat to the environment and food safety. Currently reported fluorescent methods used for MP sensing largely depend upon an enzyme. Designing a facile and specific enzyme-free MP fluorescent sensor is in great demand, which remains a challenge. Here, negatively charged Cu nanoclusters (CuNCs) anchored on positively charged melamine-formaldehyde (MF) microspheres (MF@CuNCs) through an electrostatic interaction were prepared. MF microspheres triggered aggregation-induced emission (AIE) of CuNCs and successfully circumvented the shortcomings of poor stability and low luminescence of CuNCs. The fluorescence intensity of MF@CuNCs can be quenched by p-nitrophenol produced by MP under alkaline conditions. Accordingly, a specific enzyme-free MP sensing method was constructed with MF@CuNCs. In combination with a smartphone, visually quantitative analysis of MP in a fast and portable way was also achieved. For the first time, AIE of CuNCs used for enzyme-free MP sensing was successfully explored in this work, and it is believed that this method will open a new pathway for AIE of CuNCs to be applied in various applications.


Neonatal laboratory blood sampling: comparison of results from arterial catheters with those from an automated capillary device.
To compare neonatal laboratory results from capillary blood samples drawn using the Tenderfoot automated capillary sampling device with those drawn through arterial catheters. Prospective, paired comparisons of laboratory results from capillary and arterial blood. Twenty-one infants being cared for in an NICU and having indwelling arterial catheters through which a variety of predominantly glucose-containing fluids were being administered. Statistical comparisons of paired capillary and arterial results of pH, PO2, PCO2, lactate, sodium, potassium, ionized calcium, and hematocrit. No capillary-arterial differences were observed for pH, PCO2, lactate, or sodium. Although capillary results were slightly, but significantly (p < .01), higher for potassium (+0.4 mEq/liter), ionized calcium (+0.47 mg/dl), and hematocrit (+4 percent), these differences fell within acceptable Clinical Laboratories Improvement Act (CLIA) performance criteria. Markedly lower PO2 (-30.2 mmHg) and glucose (-61 mg/dl) values were observed with capillary sampling. With the exception of results for PaO2 and plasma glucose, capillary blood drawn using the Tenderfoot automated device yields laboratory results comparable to those from blood drawn from arterial catheters as assessed by CLIA performance criteria.


Effect of phenytoin on DNA synthesis by human bone marrow.
Diphenylhydantoin (phenytoin) when incubated with human marrow interfered with the synthesis of deoxyribosenucleic acid (DNA) by those cells. This interference was dose related but was present at all concentrations, 25 microgram/ml to 100 microgram/ml. Cells unable to complete DNA synthesis would die in the marrow, lead to ineffective haemopoiesis and an increased folate requirement.


Possible role of endocannabinoids in olfactory and taste dysfunctions in Alzheimer's and Parkinson's patients and volumetric changes in the brain.
The purpose of this study is to determine the volumes of primary brain regions associated with smell and taste in Alzheimer's and Parkinson's patients and healthy controls using MR imaging and examine volumetric changes in comparison to smell/taste questionnaire and test results and endocannabinoid (EC) levels. The study included 15 AD patients with mild cognitive dysfunction scored as 18 ≤ MMSE ≤ 23, 15 PD patients with scores of 18 < MoCA < 26 and 18 ≤ MMSE ≤ 23, and 15 healthy controls. A taste and smell questionnaire was given to the participants, and their taste and smell statuses were examined using the Sniffin' Sticks smell identification test and Burghart Taste Strips. EC levels were analyzed in the blood serum samples of the participants using the ELISA method. The volumes of the left olfactory bulb (p = 0.001), left amygdala (p = 0.004), left hippocampus (p = 0.008), and bilateral insula (left p = 0.000, right p = 0.000) were significantly smaller in the Alzheimer's patients than the healthy controls. The volumes of the left olfactory bulb (p = 0.001) and left hippocampus (p = 0.009) were significantly smaller in the Parkinson's patients than the healthy controls. A significant correlation was determined between volume reduction in the left Rolandic operculum cortical region and taste dysfunction. EC levels were significantly higher in both AD (p = 0.000) and PD (p = 0.006) in comparison to the controls. Our results showed that volumetric changes occur in the brain regions associated with smell and taste in Alzheimer's and Parkinson's patients. It was observed that ECs played a role in these volumetric changes and the olfactory and taste dysfunctions of the patients.


Crystal structure of a mycobacterial secretory protein Rv0398c and in silico prediction of its export pathway.
Secretory proteins are used by pathogenic bacteria to manipulate the host systems and compete with other microorganisms, thereby enabling their survival in their host. Similar to other bacteria, secretory proteins of Mycobacterium tuberculosis also play a pivotal role in evading immune response within hosts, thereby leading to acute and latent tuberculosis infection. Prokaryotes have several classes of bacterial secretory systems out of which the Sec and Tat pathways are the most conserved in Mtb to transport proteins across the cytoplasmic membrane. Here, we report the crystal structure of a secretory protein, Rv0398c determined to 1.9 Å resolution. The protein comprises a core of antiparallel β sheets surrounded by α helices adopting a unique β sandwich fold. Structural comparison with other secretory proteins in Mtb and other pathogenic bacteria reveals that Rv0398c may be secreted via the Sec pathway. Our structural and in silico analyses thus provide mechanistic insights into the pathway adopted by Mtb to transport out secretory protein, Rv0398c which will facilitate the invasion to the host immune system.


CARM1 and BAF155: an example of how chromatin remodeling factors can be relocalized and contribute to cancer.
In a recent article, Wang and colleagues reported the discovery of a mechanism by which CARM1 regulates the genomic localization of BAF155 (a SWI/SNF subunit involved in chromatin remodeling) through post-translational methylation at R1064 arginine residues. This modification leads to the relocalization of BAF155-containing SWI/SNF complexes to regions containing genes involved in the Myc oncogenic pathway. The results presented are evidence that these interactions constitute a mechanism by which the BAF155 chromatin remodeling factor contributes to cancer.


Tumor necrosis factor α inhibition overcomes immunosuppressive M2b macrophage-induced bevacizumab resistance in triple-negative breast cancer.
Bevacizumab in neoadjuvant therapy provides a new hope of improved survival for patients with triple-negative breast cancer (TNBC) by targeting vascular endothelial growth factor in combination with chemotherapy, but curative effect is limited by bevacizumab's continuous use while mechanisms remain incompletely understood. More and more researches reported that tumor-associated macrophages mediate resistance to chemotherapy and radiotherapy in various tumors. Here we developed a TNBC model resistant to bevacizumab under bevacizumab continuous administration. It was found that proportion of a specific subset of tumor-associated macrophages characterized as M2b (CD11b+ CD86high IL10high) increased and responsible for acquired resistance to bevacizumab. Then, we showed that RAW264.7 macrophages could be polarized to M2b subtype on simultaneous exposure to bevacizumab and TLR4 ligands as occurs in the context of continuous bevacizumab treatment. Concordantly, in TLR4-deleted C57BL/10ScNJNju (TLR4lps-del) mut/mut mice with bevacizumab treatment model, it was verified that the M2b macrophage could be induced by Fc gamma receptor-TLR4 cross-talk. In MDA-MB-231-resistant tumor-bearing mice, the content of TNFα in serum kept going up consistent with CCL1, a chemokine of M2b macrophage. In vitro neutralizing tumor necrosis factor α (TNFα) could inhibit the tumor progression caused by M2b culture medium and tumor IDO1 expression. Therefore, we thought that TNFα is a key tumor-promoting effector molecule secreted by M2b macrophage. Accordingly, the curative effect of bevacizumab was proved to be significantly improved by neutralizing TNFα with anti-TNFα nanobody. This study is expected to provide theoretical and clinical evidence elucidating the drug resistance in patients receiving bevacizumab.


Tiller dynamics and self-thinning in grassland habitats.
The tiller dynamics and weight-density relationships of grasses were investigated in sown monocultures and in an established grassland both in full light and under shade. Monocultures of Festuca pratensis and Lolium perenne sown at high densities conformed to the-3/2 Power Law during establishment, but once the maximum standing had been reached the trajectory of the thinning line switched to a slope of approximately-1 when weight was plotted against density on logarithmic scales. Subsequently the populations showed a cyclical pattern of tiller weight and density bound by a line related to the maximum standing crop but also close to the-3/2 thinning line.The natural populations also showed a cyclical pattern of tiller weight and density at combinations very similar to those in the sown monocultures and close to a thinning line with an intercept (log c) of 4.4-4.7 assuming the generality of the -3/2 Power Law as w=cN -3/2. Tiller dynamics were very similar on all the plots despite differences in the species composition of each plot. The greatest seasonal variation in tiller number occurred under the shade of birch trees, perhaps due to resource depletion caused by the tree canopy during late summer and the presence of tree litter during the winter. The artificial shade treatment had little effect on plant yield but caused a significant change in the composition of the vegetation. It is suggested that mixed populations of grasses behave in essentially the same fashion as monocultures and that vegetational change might be analysed as a multispecies participation in a mutual cyclical proces of tiller death and regeneration.


Mental and physical complaints in thyroid disorders in the general population.
To test the hypothesis that untreated overt and subclinical thyroid disorders and autoimmune thyroiditis (AIT) are associated with mental and physical complaints in the general population. A total of 3790 participants from the Study of Health in Pomerania (SHIP) with no known thyroid disorders were analyzed concerning their thyroid function (TSH, FT3, FT4), autoantibodies (TPO-Ab), their thyroid structure and size and their mental and physical complaints (Zerssen Complaint Scale). Overt hyperthyroidism (prevalence: 0.4%) was associated with a significantly lower total complaint-score than euthyroid subjects. Subjects with overt hypothyroidism (0.5%), subclinical hypothyroidism (0.7%), or subclinical hyperthyroidism (1.6%) were not different from controls in their total complaints. Females with AIT showed higher scores of tachycardia and anxiety independent from their thyroid function. In non-patient samples, hyperthyroidism is associated with positive effects on self-rated mental and physical health. AIT may be associated with negative effects on health also in euthyroid subjects.


A multi-omics approach reveals molecular mechanisms by which phthalates induce cardiac defects in zebrafish (Danio rerio).
The potential risks of phthalates affecting human and animal health as well as the environment are emerging as serious concerns worldwide. However, the mechanism by which phthalates induce developmental effects is under debate. Herein, we found that embryonic exposure of zebrafish to di-(2-ethylhexyl) phthalate (DEHP) and di-butyl phthalate (DBP) increased the rate of heart defects including abnormal heart rate and pericardial edema. Changes in the transcriptional profile demonstrated that genes involved in the development of the heart, such as tbx5b, nppa, ctnt, my17, cmlc1, were significantly altered by DEHP and DBP at 50 μg/L, which agreed with the abnormal cardiac outcomes. Methylated DNA immunoprecipitation sequencing (MeDIP-Seq) further showed that significant hypomethylation of nppa and ctnt was identified after DEHP and DBP exposure, which was consistent with the up-regulation of these genes. Notably, hypermethylation on the promoter region (<1 kb) of tbx5b was found after DEHP and DBP exposure, which might be responsible for its decrease in transcription. In conclusion, phthalates have the potential to induce cardiac birth defects, which might be associated with the transcriptional regulation of the involved developmental factors such as tbx5b. These findings would contribute to understand the molecular pathways that mediated the cardiac defects caused by phthalates.


CD4:CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV-positive patients.
Absolute CD4 T cell count and plasma viral load have been established as predictors of HIV disease progression, and CD4 T cell count is used as an indicator for initiation of antiretroviral therapy. Following long-term therapy, patients generally present with significant CD4 T cell recovery contrasting with persistently elevated CD8 T cell counts, which leads to a partial restoration of CD4:CD8 ratio. This review focuses on the relevance of the CD4:CD8 ratio on clinical outcomes, immune dysfunction and HIV reservoir size in long-term treated patients. We conducted a comprehensive literature review of publications in English language using major electronic databases. Our search was focused on factors contributing to CD4:CD8 T cell ratio and clinical outcome in adult HIV-positive patients in the context of treated infection. Low CD4:CD8 ratio has been linked to ageing and acts as a predictor of mortality in the general population. This ratio may represent the combined effects of inflammation and immunological changes called "inflammaging." Although the mechanisms underlying partial correction of the CD4:CD8 ratio and persistently elevated CD8 T cell count in long-term treated patients remain poorly understood, it has been recently indicated that patients with optimal CD4 T cell recovery and low CD4:CD8 ratio still harbour increased immune activation, an immune senescent phenotype and have a higher risk of non-AIDS morbidity and mortality. This review reconsiders CD4:CD8 ratio in the light of advances in the understanding of immune dysfunction and examines its pathophysiological features and implications on clinical outcome and HIV reservoir size in long-term treated HIV-positive adults. The CD4:CD8 ratio can contribute to the immunological evaluation of treated patients in a long-term follow-up and may be applied for monitoring both immune dysfunction and viral reservoir size in immune-based clinical trials.


A case of polymyositis with dilated cardiomyopathy associated with interferon alpha treatment for hepatitis B.
Polymyositis is a rare complication of interferon alpha treatment as a result of immune-modulating role of the drug itself. In this case, interferon alpha induced polymyositis and cardiomyopathy is diagnosed in a 33-yr-old male patient with history of chronic hepatitis B. To treat hepatitis B, interferon alpha was administered until the proximal muscle weakness developed. Thereafter, sixteen cycles of immunoglobulin treatment (400 mg/kg) along with corticosteroids were instituted and led to an improvement in subjective symptoms with decreases in level of CPK and LDH. However, dilated cardiomyopathy has not improved in spite of the cessation of interferon treatment. Unlike the persistently elevated serum HBV DNA level, the serum ALT and AST levels have gradually decreased. Our case shows that clinical symptoms of polymyositis improved with steroid and immunoglobulin treatment without deterioration of the hepatitis B. To our knowledge, this is the first case of polymyositis associated with dilated cardiomyopathy after the administration of interferon in a patient with hepatitis B.


Effects of kinesiotaping combined with the motor relearning method on upper limb motor function in adults with hemiparesis after stroke.
Kinesio Taping (KT) is being widely used in neurorehabilitation as an adjuvant technique due to its therapeutic effects. The objective of this study was to determine the effects of Kinesio Taping combined with the motor relearning method on upper limb motor function in adult patients with post-stroke hemiparesis. A quasi-experimental study with pre-test and post-test in a sample of 10 adult patients with post-stroke hemiparesis, randomly assigned in two groups: experimental (n: 5) who received 12 sessions of Kinesio Taping combined with the motor relearning method and a control group (n: 5) who only received 12 sessions of the motor relearning method. Motor function was assessed through the selective movement pattern scale for adult patients with upper motor neuron injury before and after each intervention. statistically significant differences (p < 0.05) were found when comparing the means of upper limb movement patterns of the experimental group. the use of Kinesio Taping combined with the motor relearning method was encouraging for upper limb motor function in patients with spastic hemiparesis.


RNA-Seq Transcriptomic Analysis of Green Tea Polyphenols Modulation of Differently Expressed Genes in Enterococcus faecalis Under Bile Salt Stress.
Enterococcus faecalis (E. faecalis) belongs to lactic acid bacteria which can be used as a probiotic additive and feed, bringing practical value to the health of humans and animals. The prebiotic function of tea polyphenols lays a foundation for green tea polyphenols (GTP) to repair the adverse changes of E. faecalis under stress conditions. In this study, RNA-sequence analysis was used to explore the protective effect of GTP on E. faecalis under bile salt stress. A total of 50 genes were found to respond to GTP under bile salts stress, containing 18 up-regulated and 32 down-regulated genes. The results showed that multiple genes associated with cell wall and membrane, transmembrane transport, nucleotide transport and metabolism were significantly differentially expressed (P < 0.05), while GTP intervention can partly alleviate the detrimental effects of bile salt on amino acid metabolism and transport. The present study provides the whole genome transcriptomics of E. faecalis under bile salt stress and GTP intervention which help us understand the growth and mechanism of continuous adaptation of E. faecalis under stress conditions.


The effect of starch- and sucrose-reduced diet accompanied by nutritional and culinary recommendations on the symptoms of irritable bowel syndrome patients with diarrhoea.
Irritable bowel syndrome (IBS) is a common gastrointestinal condition which entails a high burden in the quality of life (QoL) of patients. Nutritional interventions have been proposed to alleviate symptoms, since still no effective treatments exist for IBS. Our aim is to analyse the feasibility of the use of starch- and sucrose-reduced diet (SSRD). In this study, we used a SSRD accompanied by nutritional and culinary recommendations to measure the effects in IBS patients with diarrhoea. In all, 34 participants completed a 4-week nutritional intervention based on SSRD. Symptoms, QoL and dietary habits were assessed by several questionnaires that were completed at the beginning, daily, after 2 weeks, at the end, and after 2 months. 85.29% of the participants reached the primary endpoint [reduction of 50 points or more in IBS-symptom severity scale (SSS)], and 58.82% the secondary endpoint (reduction of 50% or more in IBS-SSS). The relief of symptoms and improvement of the QoL were significant after 2 weeks of intervention, at the end and after 2 months. Dietary habits were consistent with the diet and high adherence was achieved. SSRD and individualized nutritional and culinary guidance improved symptoms and QoL of IBS patients with diarrhoea, with a high adherence.


Ultrasound evaluation of intima-media thickness of carotid arteries in adults with primary hypertension at Ibadan, Nigeria.
Ultrasound measured Carotid Intima-Media Thickness (CIMT) is a simple and inexpensive tool for assessing the cumulative effects of hypertension on the carotid arterial walls. It is also an independent predictor of future myocardial infarction and stroke risk. This study compared ultrasound measured CIMT in hypertensive adults with non-smoking normotensive controls. It also documented variations in CIMT with subjects' age and sex. Hypertensives (120) of both sexes aged 18 years and above were recruited from the Hypertension Clinic at University College Hospital (UCH) Ibadan. Normotensive controls (120) were also recruited from the general public. The CIMT was measured on B- mode ultrasound using the technique of 'Multiple Carotid Sites Measurement' Mean CIMT values were 0.756 mm ± 0.130 and 0.751 mm ± 0.129 for the hypertensive group and 0.638 mm ± 0.088 and 0.67 0mm ± 0.107 for the control group on the left and right sides respectively (P=0.000). Higher CIMT values were noted among male hypertensive subjects (P=0.030). CIMT values also showed positive correlation with subjects' age. There was a significant difference in CIMT for hypertensives when compared with normotensives in the study area. CIMT also varies with subjects' age and sex.


The involvement of NLRP3 inflammasome in CUMS-induced AD-like pathological changes and related cognitive decline in mice.
Numerous studies have found that inhibiting the expression of NLRP3 inflammasome can significantly improve depressive-like behaviors in mice, but the research on its effect on cognitive decline in depression and its mechanism is still lacking. This study aimed to elucidate the role of NLRP3 inflammasome in cognitive decline in depression and explore the common neuro-immunological mechanisms of depression and Alzheimer's disease (AD). Male C57BL/6 mice were subjected to chronic unpredictable mild stress (CUMS) for 5 weeks, treatment group was administered with the NLRP3 inhibitor MCC950 (10 mg/kg, i.p.), fluoxetine served as positive control. Then, the mice were assessed for cognitive behaviors and depression-like behaviors, and changes of microglia and neurons in hippocampus and levels of Aβ metabolic pathway and tau protein were measured. To explore the mechanism of NLRP3 activation on neurons, we performed in vitro studies using BV2 microglia and mouse primary neurons. Furthermore, we focused on the role of NLRP3 inflammasome in the function of neurons and the expression of AD pathological indicators. CUMS induced depressive-like behaviors and cognitive decline in mice, which could be reversed by inhibiting NLRP3 inflammasome. MCC950, a specific NLRP3 inhibitor, alleviated CUMS-induced neuron injury and AD-like pathological changes, including the abnormal expression of Aβ metabolic pathway and the hyper-phosphorylation of tau protein. LPS (1 μg/mL) + ATP (1 mM) treatment activated the expression of NLRP3 inflammasome and IL-1β in vitro. In vitro experiment also proved that inhibiting the expression of NLRP3 inflammasome in microglia can restore the Aβ metabolic pathway to normal, decrease neuronal tau protein phosphorylation and protect neurons. Inhibition of NLRP3 inflammasome effectively alleviated CUMS-induced depressive-like behaviors and cognitive decline in mice, and inhibited the activation of AD physiological indicators.


Reference values for airway resistance in newborns, infants and preschoolers from a Latin American population.
Several studies have determined reference values for airway resistance measured by the interrupter technique (Rint) in paediatric populations, but only one has been done on Latin American children, and no studies have been performed on Mexican children. Moreover, these previous studies mostly included children aged 3 years and older; therefore, information regarding Rint reference values for newborns and infants is scarce. Rint measurements were performed on preschool children attending eight kindergartens (Group 1) and also on sedated newborns, infants and preschool children admitted to a tertiary-level paediatric hospital due to non-cardiopulmonary disorders (Group 2). In both groups, Rint values were inversely associated with age, weight and height, but the strongest association was with height. The linear regression equation for Group 1 (n = 209, height 86-129 cm) was Rint = 2.153 - 0.012 × height (cm) (standard deviation of residuals 0.181 kPa/L/s). The linear regression equation for Group 2 (n = 55, height 52-113 cm) was Rint = 4.575 - 0.035 × height (cm) (standard deviation of residuals 0.567 kPa/L/s). Girls tended to have slightly higher Rint values than boys, a difference that diminished with increasing height. In this study, Rint reference values applicable to Mexican children were determined, and these values are probably also applicable to other paediatric populations with similar Spanish-Amerindian ancestries. There was an inverse relationship between Rint and height, with relatively large between-subject variability.


Ultrasound diagnosis of fracture-separation of the distal humeral chondro-epiphysis: a rare but important condition that a radiologist must not miss.
Fracture-separation of the distal humeral epiphysis is a rare condition known to be associated with non-accidental injury. Ultrasound is useful in diagnosis of this important disease entity with the humeral epiphysis not yet ossified.


Candidatus "Thiodictyon syntrophicum", sp. nov., a new purple sulfur bacterium isolated from the chemocline of Lake Cadagno forming aggregates and specific associations with Desulfocapsa sp.
Strain Cad16(T) is a small-celled purple sulfur bacterium (PSB) isolated from the chemocline of crenogenic meromictic Lake Cadagno, Switzerland. Long term in situ observations showed that Cad16(T) regularly grows in very compact clumps of cells in association with bacteria belonging to the genus Desulfocapsa in a cell-to-cell three dimensional structure. Previously assigned to the genus Lamprocystis, Cad16(T), was here reclassified and assigned to the genus Thiodictyon. Based on comparative 16S rRNA gene sequences analysis, isolate Cad16(T) was closely related to Thiodictyon bacillosum DSM234(T) and Thiodictyon elegans DSM232(T) with sequence similarities of 99.2% and 98.9%, respectively. Moreover, matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) analysis separated Cad16(T) from other PSB genera, Lamprocystis and Thiocystis. Major differences in cell morphology (oval-sphere compared to rod-shaped) and arrangement (no netlike cell aggregates), carotenoid group (presence of okenone instead of rhodopinal), chemolithotrophic growth as well as the ability to form syntrophic associations with a sulfate-reducing bacteria of the genus Desulfocapsa suggested a different species within the genus Thiodictyon. This isolate is therefore proposed and described as Candidatus "Thiodictyon syntrophicum" sp. nov., a provisionally novel species within the genus Thiodictyon.


A genome-wide association study of morphometric traits in dromedaries.
Investigating genomic regions associated with morphometric traits in camels is valuable, because it allows a better understanding of adaptive and productive features to implement a sustainable management and a customised breeding program for dromedaries. With a genome-wide association study (GWAS) including 96 Iranian dromedaries phenotyped for 12 morphometric traits and genotyped-by-sequencing (GBS) with 14,522 SNPs, we aimed at identifying associated candidate genes. The association between SNPs and morphometric traits was investigated using a linear mixed model with principal component analysis (PCA) and kinship matrix. With this approach, we detected 59 SNPs located in 37 candidate genes potentially associated to morphometric traits in dromedaries. The top associated SNPs were related to pin width, whither to pin length, height at whither, muzzle girth, and tail length. Interestingly, the results highlight the association between whither height, muzzle circumference, tail length, whither to pin length. The identified candidate genes were associated with growth, body size, and immune system in other species. We identified three key hub genes in the gene network analysis including ACTB, SOCS1 and ARFGEF1. In the central position of gene network, ACTB was detected as the most important gene related to muscle function. With this initial GWAS using GBS on dromedary camels for morphometric traits, we show that this SNP panel can be effective for genetic evaluation of growth in dromedaries. However, we suggest a higher-density SNP array may greatly improve the reliability of the results.


Numerical study on the effect of steady axial flow development in the human aorta on local shear stresses in abdominal aortic branches.
The three-dimensional flow through a rigid model of the human abdominal aorta complete with iliac and renal arteries was predicted numerically using the steady-state Navier Stokes equations for an incompressible. Newtonian fluid. The model adapted for our purposes was determined from data obtained from cine-CT images taken of a glass chamber that was constructed based on anatomical averages. The iliac arteries had a bifurcation angle of approximately 35 and a branch-to-trunk area ratio of 1.27. whereas the renal arteries had left and right branch angles of 40 and an area ratio of 0.73. The numerical tool FLOW3D (AEA Industrial Technology, Oxfordshire, UK) utilized body-fitted coordinates and a finite volume discretization procedure. Purely axial velocity profiles were introduced at the entrance of the model for a range of cardiac outputs. The four-branch numerical model developed for this investigation produced flow and shear conditions comparable to those found in other reported works. The total wall shear stress distribution in the iliac and renal arteries followed standard trends. with maximum shear stresses occurring in the apex region and lower shear stresses occurring along the lateral walls. Shear stresses and flow rate ratios in the downstream arteries were more effected by inlet Re than the upstream arteries. These results will be used to compare further simulations which take into effect the rotational component of flow which is present in the aortic arch.


Characterization of the Genetic System of the Xylose-Fermenting Yeast Pichia stipitis
High mutant frequencies indicated that the wild-type strains of Pichia stipitis are haploid. Sporulation ability of these clones pointed to a homothallic life cycle. Mating was induced by cultivation under nutritionally poor conditions on malt extract medium. Conjugation was followed immediately by sporulation. However, hybrids could be rescued by transferring the nascent zygotes to complete medium before meiosis had started. Under rich nutritional conditions, hybrids were mitotically stable and did not sporulate. The segregation pattern of auxotrophic markers of diploid zygotes indicated regular meiosis, although asci contained preferentially spore dyads.


Charting the travels of copper in eukaryotes from yeast to mammals.
Throughout evolution, all organisms have harnessed the redox properties of copper (Cu) and iron (Fe) as a cofactor or structural determinant of proteins that perform critical functions in biology. At its most sobering stance to Earth's biome, Cu biochemistry allows photosynthetic organisms to harness solar energy and convert it into the organic energy that sustains the existence of all nonphotosynthetic life forms. The conversion of organic energy, in the form of nutrients that include carbohydrates, amino acids and fatty acids, is subsequently released during cellular respiration, itself a Cu-dependent process, and stored as ATP that is used to drive a myriad of critical biological processes such as enzyme-catalyzed biosynthetic processes, transport of cargo around cells and across membranes, and protein degradation. The life-supporting properties of Cu incur a significant challenge to cells that must not only exquisitely balance intracellular Cu concentrations, but also chaperone this redox-active metal from its point of cellular entry to its ultimate destination so as to avert the potential for inappropriate biochemical interactions or generation of damaging reactive oxidative species (ROS). In this review we chart the travels of Cu from the extracellular milieu of fungal and mammalian cells, its path within the cytosol as inferred by the proteins and ligands that escort and deliver Cu to intracellular organelles and protein targets, and its journey throughout the body of mammals. This article is part of a Special Issue entitled: Cell Biology of Metals.


Correction: Considerations for an Individual-Level Population Notification System for Pandemic Response: A Review and Prototype.
[This corrects the article DOI: 10.2196/19930.].


Expanded Autoantibody Profiles for Subsetting of Native American, African American, and European American Patients With Systemic Lupus Erythematosus.
Many Native American (NA) patients with systemic lupus erythematosus (SLE) do not exhibit the classical SLE autoantibody profiles of European American (EA) and African American (AA) patients with SLE. The poorer SLE disease outcomes noted in NA patients highlights a need for more equitable diagnostic and prognostic tools for NA patients with SLE. The objective was to identify informative autoantibody profiles for NA, AA, and EA patients with SLE using an expanded set of autoantigens. Sera from 49 NA, 49 AA, and 49 EA age-, sex-, and antinuclear autoantibody titer-matched patients with SLE who met the American College of Rheumatology classification criteria and 10 ethnicity-, sex-, and age-matched controls were tested for autoantibody reactivity by autoantigen microarrays. Autoantibodies that were significantly elevated in patients with SLE compared with ethnicity-specific controls were selected for hierarchical clustering. Differences in clinical criteria between patient clusters were determined by Fisher's exact test and corrected for multiple comparisons. NA, AA, and EA patients with SLE each had a cluster distinguished by higher levels of anti-Ro52 and another cluster distinguished by nucleic acid-specific autoantibodies. Additional clusters were distinguished in NA patients by elevated extracellular matrix autoantibodies and were distinguished in AA patients by elevated Sm/RNP autoantibody and elevated nucleolin/histone autoantibody. Two EA patient clusters with similar nucleic acid- and Ro52-specific autoantibodies were distinguished by either high or low histone 2A reactivity. Renal manifestations trended higher in the NA Ro52 cluster and were significantly enriched in the AA nucleolin/histone cluster. The AA nucleolin/histone cluster and EA H2A cluster had higher disease activity. Expanded autoantibody profiles can identify informative subsets of patients with SLE.


Acute hemodynamic effect of a vascular antagonist of vasopressin in patients with congestive heart failure.
To assess the role of arginine vasopressin (AVP) in congestive heart failure (CHF), 10 patients with CHF refractory to conventional treatment were studied before and 60 minutes after intravenous administration of 5 micrograms/kg of d(CH2)5Tyr(Me)AVP, a specific antagonist of AVP at the vascular receptor level. Heart rate, systemic arterial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac index by thermodilution and cutaneous blood flow by laser-Doppler technique were measured. In 9 patients with no significant hemodynamic and cutaneous blood flow response to the AVP antagonist, baseline values (mean +/- standard deviation) were: heart rate, 77 +/- 14 beats/min; systemic arterial pressure, 120/79 +/- 18/8 mm Hg; pulmonary arterial pressure, 42/21 +/- 12/8 mm Hg; pulmonary capillary wedge pressure, 19 +/- 7 mm Hg; cardiac index, 2.2 +/- 0.6 liters/min/m2; plasma AVP, 2.3 +/- 0.8 pg/ml; and plasma osmolality, 284 +/- 14 mosm/kg H2O. The tenth patient had the most severe CHF. His plasma AVP level was 55 pg/ml and plasma osmolality was 290 mosm/kg. He responded to the AVP antagonist with a decrease in systemic arterial pressure from 115/61 to 79/41 mm Hg, in pulmonary arterial pressure from 58/31 to 33/13 mm Hg and in pulmonary capillary wedge pressure from 28 to 15 mm Hg. Simultaneously, cardiac index increased from 1.1 to 2.2 liters/min/m2 and heart rate from 113 to 120 beats/min; cutaneous blood flow increased 5-fold.(ABSTRACT TRUNCATED AT 250 WORDS)


Changes in the nuclei and chloroplasts in cells of big bud-infected tomatoes.
Electron-microscopic studies of ultrathin sections of young tomato shoots infected by big bud showed that the mycoplasma causes pathological changes in the cell nucleus and chloroplasts.


Is bog water chemistry affected by increasing N and S deposition from oil sands development in Northern Alberta, Canada?
Nitrogen and sulfur emissions from oil sands operations in northern Alberta, Canada have resulted in increasing deposition of N and S to the region's ecosystems. To assess whether a changing N and S deposition regime affects bog porewater chemistry, we sampled bog porewater at sites at different distances from the oil sands industrial center from 2009 to 2012 (10-cm intervals to a depth of 1 m) and from 2009 to 2019 (top of the bog water table only). We hypothesized that: (1) as atmospheric N and S deposition increases with increasing proximity to the oil sands industrial center, surface porewater concentrations of NH4+, NO3-, DON, and SO42- would increase and (2) with increasing N and S deposition, elevated porewater concentrations of NH4+, NO3-, DON, and SO42- would be manifested increasingly deeper into the peat profile. We found weak evidence that oil sands N and S emissions affect bog porewater NH4+-N, NO3--N, or DON concentrations. We found mixed evidence that increasing SO42- deposition results in increasing porewater SO42- concentrations. Current SO42- deposition, especially at bogs closest to the oil sands industrial center, likely exceeds the ability of the Sphagnum moss layer to retain S through net primary production, such that atmospherically deposited SO42- infiltrates downward into the peat column. Increasing porewater SO42- availability may stimulate dissimilatory sulfate reduction and/or inhibit CH4 production, potentially affecting carbon cycling and gaseous fluxes in these bogs.


Congenital Aural Stenosis: Clinical Features and Long-term Outcomes.
The aim of the present study was to comprehensively evaluate the clinical features and long-term outcomes of congenital aural stenosis (CAS). This study presents a retrospective review of patients who underwent meatoplasty for CAS at a tertiary referral hospital from 2008 to 2015. A total of 246 meatoplasty procedures were performed on 232 patients in the present study. We performed multivariate regression analysis. Except in the age < 6 years group, no significant difference was observed among different age groups for cholesteatoma formation, p > 0.05. Except for the stenosis of the external auditory canal (EAC) (>4 mm) group, the other stenosis of EAC groups were not associated with cholesteatoma formation, p > 0.05. Postoperative air-bone gaps (ABG) less than 30 dB occurred in 77.3% (99/128) of the patients, and the Jahrsdoerfer score was associated with postoperative ABG, p < 0.001. The complication rate of CAS was 13.8% (20/144), and males showed a higher risk for postoperative complications (OR, 6.563; 95% CI, 1.268-33.966, p = 0.025). These results indicate that meatoplasty was an effective surgical intervention for CAS, showing a stable hearing outcome with prolonged follow-up. There was no significant difference between the cholesteatoma and no cholesteatoma groups for hearing outcomes, p > 0.05.