In Vitro Fertilization Outcomes After Placement of Essure Microinserts in Patients With Hydrosalpinges Who Previously Failed In Vitro Fertilization Treatment: A Multicenter Study.
To investigate whether hysteroscopic proximal tubal occlusion with Essure microinserts (Conceptus Inc.; Bayer, AG, North Rhine-Westphalia, Germany) can improve pregnancy rates in patients with hydrosalpinges who had failed in vitro fertilization (IVF) treatment. A prospective cohort study. University-affiliated tertiary centers. Twenty-four consecutive women with hydrosalpinges who had failed IVF treatment were included. Hysteroscopic placement of Essure microinserts for hydrosalpinx blockage followed by IVF treatment. Ongoing pregnancy and live birth rates were recorded. Of the 24 patients undergoing a total of 42 IVF cycles after Essure insertion, 18 (75% of patients and 42.8% of IVF cycle attempts) conceived and 16 delivered live births (66.6% of patients and 38.1% of IVF cycle attempts). Hysteroscopic proximal occlusion of hydrosalpinges with Essure microinserts is a valuable alternative to laparoscopic salpingectomy, resulting in reasonable pregnancy rates.


Regulation of expression of the mitochondrial and cytosolic forms of aconitase in maize leaves via phytochrome.
Regulation of expression and methylation of promoters of two aconitase (EC 126.96.36.199) genes by light have been investigated in maize (Zea mays L.) in relation to the involvement of phytochrome. Transferring of plants from light to darkness resulted in the stimulation of aconitase activity in mitochondria and in its suppression in the cytosol. Irradiation by red light reversed aconitase activity to the levels observed under white light while far red light reverted the effect of red light. Electrophoretic staining of aconitase activity revealed the preference of the cytosolic form in white and red light and of the mitochondrial form in darkness and in far red light. Both forms of aconitase were purified, the mitochondrial form revealed lower affinity to citrate and higher to isocitrate as compared to the cytosolic form. The study of the aconitase gene Aco1 encoding the mitochondrial form revealed its low expression and high promoter methylation in the light and upon irradiation by red light as compared to high expression and low promoter methylation in darkness and in far red light. The pattern of expression and promoter methylation of the gene Aco2 encoding the cytosolic form was opposite. It is concluded that expression of the mitochondrial and cytosolic forms of aconitase is under control of light via phytochrome in opposite ways at the level of promoter methylation. Light inhibits expression of the mitochondrial aconitase, while it stimulates expression of the cytosolic aconitase which is important for directing citrate exported from mitochondria to the synthesis of amino acids.


Immunization with cholinergic cell bodies induces histopathological changes in rat brains.
We have previously shown that sera from patients with Alzheimer's disease (AD) contain antibodies to the cell bodies (perikarya; PK) of purely cholinergic Torpedo neurons, and that repeated immunization of rats with this neuronal preparation for over a year induces learning and memory impairments. In the present study, we examined the brain morphology of cholinergic PK immunized rats relative to controls. Immunohistochemical studies of the brains of these rats revealed the accumulation of IgG in specific areas, such as, the hippocampus. Parallel histochemical studies demonstrated significant changes in the hippocampus, and in white matter areas. They included large vacuoles and necrotic nuclei in the granular layer of the dentate gyrus, tangle-like appearance in some pyramidal neurons of the hippocampus, and vacuolar degeneration accompanied by oligodendroglia hypertrophy in white matter tracts, such as, the corpus callosum and fimbria. In contrast, immunization with Torpedo cholinergic nerve terminals, that has no cognitive effects on the rat, also did not induce brain morphological changes. These findings suggest that the learning and memory deficits induced by immunizing rats with cholinergic PK are related to the observed brain morphological changes, and support the hypothesis that the antibodies to cholinergic neurons found in the sera of AD patients may play a role in neuronal degeneration in this disease.


Outcomes after percutaneous coronary intervention in contemporary Australian practice: insights from a large multicentre registry.
To examine short- and medium-term outcomes of percutaneous coronary interventions (PCIs), with a focus on comparing drug-eluting stents (DESs) with bare-metal stents (BMSs). Retrospective analysis of data from the Melbourne Interventional Group (MIG) registry, a large multicentre Australian registry. The study cohort consisted of 6364 consecutive patients undergoing 7167 PCIs between April 2004 and August 2007. Clinical events including death, myocardial infarction (MI), target lesion revascularisation (TLR), target vessel revascularisation (TVR) and major adverse cardiac events (MACE) (a composite of death, MI and TVR), at 30 days and at 12 months. The cohort was predominantly male (74%), with a mean age of 64.7 years (SD, 12.0 years). DESs were used in 3482 (51.4%) of PCIs. In the overall cohort, rates of clinical events were low at 30 days: mortality (1.9%), MI (2.4%), TLR (2.0%), TVR (2.4%) and MACE (5.7%). At 12 months, event rates were: mortality (5.2%), MI (6.0%), TLR (5.8%), TVR (8.2%) and MACE (16.2%). Patients receiving DESs had similar mortality rates to those receiving BMSs (4.0% v 6.0%; P = 0.62 [propensity score-adjusted]); late thrombosis rates were also similar in the two groups (0.8% v 1.1%; P = 0.38). The proportion of patients receiving DESs fell significantly over time, from 54.9% in the first 24 months to 44.7% in the last 15 months of the study period (P < 0.01). Independent predictors of 12-month mortality included diabetes, renal failure, ST-segment-elevation MI and cardiogenic shock. Our clinical event rates were comparable with international registry outcomes. Rates of mortality and stent thrombosis were no higher in patients with DESs than those with BMSs. Although DESs were used in about half the procedures (preferentially for higher-risk lesions), recent trends suggest their use is in decline.


Perceptual multistability in figure-ground segregation using motion stimuli.
In a series of experiments using ambiguous stimuli, we investigate the effects of displaying ordered, discrete series of images on the dynamics of figure-ground segregation. For low frame presentation speeds, the series were perceived as a sequence of discontinuous, static images, while for high speeds they were perceived as continuous. We conclude that using stimuli varying continuously along one parameter results in stronger hysteresis and reduces spontaneous switching compared to matched static stimuli with discontinuous parameter changes. The additional evidence that the size of the hysteresis effects depended on trial duration is consistent with the stochastic nature of the dynamics governing figure-ground segregation. The results showed that for continuously changing stimuli, alternative figure-ground organizations are resolved via low-level, dynamical competition. A second series of experiments confirmed these results with an ambiguous stimulus based on Petter's effect.


N-methyl-N'-nitro-N-nitrosoguanidine: the effect on migration and cGMP level of neutrophils.
N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) causes a concentration-dependent increase of the cGMP level in rabbit peritoneal neutrophils. MNNG has a strong chemokinetic effect on neutrophils. In addition the compound also possesses a moderate chemotactic effect. The potentiating effect of MNNG on neutrophil migration is completely inhibited by pertussis toxin. The results support the view that in neutrophils cGMP is involved in chemokinesis and chemotaxis and that the cGMP-mediated potentiation of migration is controlled by a pertussis toxin-sensitive G-protein.


In vitro simulation of the liver first-pass effect with biotransformation-competent HepG2 cells to study effects of MG-132 on liver and cancer cells.
Liver biotransformation is the major route for drug metabolism in humans, often catalysed by cytochrome P450 (CYP) enzymes. This first-pass effect can lead to hepatotoxicity and influences the bioavailability of drugs. We aimed to establish in vitro culture systems simulating the liver first-pass to study effects of the proteasome inhibitor MG-132 simultaneously on hepatocytes and cancer cells. The first-pass effect was simulated by conditioned medium transfer (CMT) from pre-treated HepG2 CYP3A4-overexpressing cells to either pancreatic cancer cell line PANC-1 or primary colon cancer cells, and by indirect co-culture (CC) of liver and cancer cells in a shared medium compartment. Experimental proteasome inhibitor MG-132 was used as test substance as it is detoxified by CYP3A4. Cancer cells showed higher viabilities in the first-pass simulation by CMT and CC formats when compared to monocultures indicating effective detoxification of MG-132 by HepG2 CYP3A4-overexpressing cells. HepG2-CYP3A4 cells showed reduced viabilites after treatment with MG-132. We successfully established two different culture systems to simulate the liver first-pass effect in vitro. Such systems easily allow to study drug effects simultaneously on liver and on target cancer cells. They are of great value in pre-clinical cancer research, pharmaceutical research and drug development.


Obesity Represses CYP2R1, the Vitamin D 25-Hydroxylase, in the Liver and Extrahepatic Tissues.
Low plasma level of 25-hydroxyvitamin D (25-OH-D), namely vitamin D deficiency, is associated with obesity and weight loss improves 25-OH-D status. However, the mechanism behind obesity-induced vitamin D deficiency remains unclear. Here, we report that obesity suppresses the expression of cytochrome P450 (CYP) 2R1, the main vitamin D 25-hydroxylase, in both mice and humans. In humans, weight loss induced by gastric bypass surgery increased the expression of CYP2R1 in the s.c. adipose tissue suggesting recovery after the obesity-induced suppression. At the same time, CYP27B1, the vitamin D 1α-hydroxylase, was repressed by the weight loss. In a mouse (C57BL/6N) model of diet-induced obesity, the plasma 25-OH-D was decreased. In accordance, the CYP2R1 expression was strongly repressed in the liver. Moreover, obesity repressed the expression of CYP2R1 in several extrahepatic tissues, the kidney, brown adipose tissue, and testis, but not in the white adipose tissue. Obesity had a similar effect in both male and female mice. In mice, obesity repressed expression of the vitamin D receptor in brown adipose tissue. Obesity also upregulated the expression of the vitamin D receptor and CYP24A1 in the s.c. adipose tissue of a subset of mice; however, no effect was observed in the human s.c. adipose tissue. In summary, we show that obesity affects CYP2R1 expression both in the mouse and human tissues. We suggest that in mouse the CYP2R1 repression in the liver plays an important role in obesity-induced vitamin D deficiency. Currently, it is unclear whether the CYP2R1 downregulation in extrahepatic tissues could contribute to the obesity-induced low plasma 25-OH-D, however, this phenomenon may affect at least the local 25-OH-D concentrations. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.


On the importance of marine meiofauna for benthos communities.
1. In sublittoral sediments of silty sand live about 55000-1300000 meiofauna animals, which is a minimum figure because methods are not absolutely efficient. 2. Meiofauna biomass ranges from 0.2 to 2.0 g wet weight in sublittoral silty sand, that is about 3% of macrofauna biomass. 3. A higher percentage of meiofauna biomass is recorded from brackish water regions, intertidal beaches and from the deep sea, where meiofauna and macrofauna biomass are of the same magnitude. 4. Oxygen consumption in meiofauna animals is between 200 and 2000, in small macrofauna between 200 and 500, and in larger macrofauna between 10 and 100 mm3 O2/h/g wet weight. 5. The assumption is forwarded that in general meiofauna has a metabolism five times more active than that of macrofauna. 6. Generation time in meiofauna lasts from a few days as was observed in cultures, to one or a few years, as was observed in natural populations. For a generalization the guess is forwarded that three generations per year would be an average meiofauna value. 7. Life cycle turnover rate as calculated from life cycle models of two nematodes is 2.2-3. Multiplied by three annual generations results in an average annual turnover rate of about 9 for meiobenthos, which is about five times more than that in macrobenthos. 8. If one compares meiobenthos and macrobenthos, meiobenthos importance in terms of food consumed and in terms of biomass provided for the food chain is 15% in a community like sublittoral silty sand, although meiobenthos in terms of standing stock is just 3% of macrobenthos.


Improving penicillin biosynthesis in Penicillium chrysogenum by glyoxalase overproduction.
Genetic engineering of fungal cell factories mainly focuses on manipulating enzymes of the product pathway or primary metabolism. However, despite the use of strong promoters or strains containing the genes of interest in multiple copies, the desired strongly enhanced enzyme levels are often not obtained. Here we present a novel strategy to improve penicillin biosynthesis by Penicillium chrysogenum by reducing reactive and toxic metabolic by-products, 2-oxoaldehydes. This was achieved by overexpressing the genes encoding glyoxalase I and II, which resulted in a 10% increase in penicillin titers relative to the control strain. The protein levels of two key enzymes of penicillin biosynthesis, isopenicillin N synthase and isopenicillin N acyltransferase, were increased in the glyoxalase transformants, whereas their transcript levels remained unaltered. These results suggest that directed intracellular reduction of 2-oxoaldehydes prolongs the functional lifetime of these enzymes.


Regional anesthesia for office-based procedures in otorhinolaryngology.
Local and topical anesthetic techniques have long been used for office-based procedures in otorhinolaryngology. There are numerous advantages to using local and topical anesthesia for office-based procedures, including a shorter recovery period, decreased health care cost, and the maintenance of a conscious patient who can communicate with the surgeon and maintain his or her own airway during the procedure. In this manuscript, we review the local and topical anesthetic techniques that can be used for otorhinolaryngic procedures including anesthesia of the external face, ear, nose, oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx.


Overexpression of any fibrinogen chain by Hep G2 cells specifically elevates the expression of the other two chains.
Earlier studies showed that overexpression of B beta fibrinogen chains, by transfection of Hep G2 cells with B beta cDNA, specifically enhanced the synthesis of all three fibrinogen chains (Roy, S. N., Mukhopadhyay, G., and Redman, C. M. (1990) J. Biol. Chem. 265, 6389-6393). To determine whether overexpression of any of the three component chains of fibrinogen affects the synthesis of the other two chains, we developed stable Hep G2 cell lines transfected with individual fibrinogen chain cDNAs. As a control, cells were also transfected with expression vector, which did not contain fibrinogen cDNA. Transfection with any fibrinogen cDNA increased the synthesis of all three fibrinogen chains but not of other plasma proteins. Hep G2 cells transfected with B beta cDNA produced 3-4-fold more fibrinogen than control cells, and cells transfected with A alpha or gamma cDNA made about 2-fold more fibrinogen. Northern blot analyses showed that levels of all 3 fibrinogen mRNAs were increased and were highest in Hep G2-B beta cells. Nuclear run-on transcription assays demonstrated that increased expression of the chains was due to increased transcriptional activity. These studies show that transcription of the three fibrinogen chains is tightly linked, and increased expression of any chain specifically leads to increased synthesis of the other two chains.


Inducible lymphoid clusters, iSALTs, in contact dermatitis: a new concept of acquired cutaneous immune responses.
Antigen presentation to peripheral memory T cells is a key step in the prompt elicitation of acquired immune responses. In the mucosa, specific sentinel lymphoid tissues called mucosa-associated lymphoid tissue serve as antigen presentation sites. Correspondingly, the concept of skin-associated lymphoid tissue (SALT) has been proposed in the 1980s. However, the details of SALT have not been clarified so far. Recently, the live imaging analysis using two photon microscopes are developed. Here, we have identified inducible lymphoid clusters in the skin, we called it inducible SALTs (iSALTs), using a murine contact hypersensitivity model. In the elicitation phase, dendritic cells (DCs) formed clusters and interacted for several hours with effector memory T cells in the dermis. This interaction was essential for proliferation and activation of effector memory T cells in situ in an antigen dependent manner. Interestingly, DC clusters were abrogated by depletion of skin macrophages. Furthermore, IL-1 treatment induced CXCL2 production from macrophages and DC clusters were suppressed with the blockade of IL-1R or CXCR2. Taken together, this sustained conjugation between DCs and memory T cells, iSALTs, is essential for establishment of the effector phase in acquired cutaneous immunity.


Histopathological changes in insulin, glucagon and somatostatin cells in the islets of NOD mice during cyclophosphamide-accelerated diabetes: a combined immunohistochemical and histochemical study.
The cyclophosphamide model of accelerated diabetes in the NOD mouse is a useful model of insulin-dependent diabetes mellitus (IDDM). Knowledge on the progressive destruction of beta cells and the fate of other islet endocrine cell-types in this model is sparse. We employed immunohistochemistry and histochemistry, to study temporal changes in islet cell populations, insulitis and glucose transporter-2 expression during cyclophosphamide administration. Cyclophosphamide was administered to day 95 female NOD mice and the pancreas studied at days 0 ( = day 95), 4, 7, 11 and 14 after treatment and in age-matched control mice. At day 0, a majority of the endocrine cells were insulin-positive. Glucagon and somatostatin cells were mostly in the islet periphery and also internally. In the cyclophosphamide group, insulitis was moderate at day 0, declined at day 4 but increased progressively from day 7. The extent of insulitis in treated mice which were diabetes-free at day 14 was comparable to age-matched control mice. From day 11, the marked increase in insulitis correlated with a reciprocal decline in the extent of insulin immunostained islet area. At day 14, the mean insulin area per islet was markedly less in diabetic mice than in age-matched non-diabetic treated and controls. At diabetes, some islets showed co-expression of glucagon and insulin. Our studies suggest that the mean number of glucagon or somatostatin cells per islet does not vary during the study. Glucose transporter-2 immunolabelling was restricted to beta cells but declined in those adjacent to immune cells. We conclude that in the cyclophosphamide model, there is specific and augmented destruction of beta cells immediately prior to diabetes onset. We speculate that the selective loss of glucose transporter-2 shown in this study suggests the existence of a deleterious gradient close to the immune cell and beta cell surface boundary.


Unusual effects of crowders on heme retention in myoglobin.
Myoglobin (Mb) undergoes pronounced heme loss under denaturing conditions wherein the proximal histidine gets protonated. Our data show that macromolecular crowding agents (both synthetic and protein based) can appreciably influence the extent of heme retention in Mb. Interestingly, glucose and sucrose, the monomeric constituents of dextran and ficoll-based crowders were much more effective in preventing heme dissociation of Mb, albeit, at much higher concentrations. The protein crowders BSA and lysozyme show very interesting results with BSA bringing about the maximum heme retention amongst all the crowding agents used while lysozyme induced heme dissociation even in the native state of Mb. The stark difference that these protein crowders exhibit when interacting with the heme protein is a testament to the varied interaction potentials that a test protein might be exposed to in the physiological (crowded) milieu.


Production of tumor necrosis factor in spinal cord following traumatic injury in rats.
Production of tumor necrosis factor (TNF) in the spinal cord following traumatic injury has been studied. In these experiments, the level of TNF was examined in the homogenate of the spinal cord, cerebrospinal fluid (CSF) and serum (n = 56). TNF could be detected in the injured spinal cord but not in the normal spinal cord. The TNF level increased in the spinal cord after the injury. At the lesion site, a maximal TNF concentration was observed 1 h after the injury, and the TNF concentration remained at this level until 8 h after the injury. Thereafter, it decreased gradually. However, TNF still could be detected 72 h after the injury. No TNF could be detected in the CSF and serum, collected from rats both with and without spinal cord injury (SCI). This study thus suggests that TNF is produced locally in the spinal cord following traumatic injury, and this TNF production is caused by the injury. The present results also demonstrate that TNF production is an acute and rapid reaction in the spinal cord following traumatic injury.


The etiology of acrophobia and its relationship to severity and individual response patterns.
The acquisition of acrophobia in a large clinical sample was investigated. 148 patients from a university-based height phobia clinic and 148 age and sex matched non-phobic controls served as Ss. Subjects were assessed with a battery of measures including the Acrophobia Questionnaire [Cohen, D. C. (1977), Behavior Therapy, 18, 17-23], self-rating of severity [Marks, I.M. & Mathews, A. M. (1979) Behaviour Research and Therapy, 17, 263-267] global rating of severity [Michelson, L. (1986), Behaviour Research and Therapy, 24, 263-275], origins questionnaire [Menzies, R. G. & Clarke, J. C. (1993a) Behaviour Research and Therapy, 31, 355-365], and a height avoidance test. Results obtained question the significance of simple associative-learning events in the acquisition of fear of heights. Only 11.5% of fearful Ss were classified as directly conditioned cases. Furthermore, no differences between groups were found in the proportion of Ss who knew other height-fearfuls, had experienced relevant associative-learning events, or the ages at which these events had occurred. Finally, no relationships between mode of acquisition and severity or individual response patterns were obtained. In general, the data were consistent with the non-associative, Darwinian accounts of fear acquisition that continue to attract theorists from a variety of backgrounds [e.g. Bowlby, J. (1975) Attachment and Loss; Clarke, J.C. & Jackson, J. A. (1983) Hypnosis and behavior therapy: the treatment of anxiety and phobia; Marks, I. M. (1987) Fears, phobias and rituals: panic, anxiety and their disorders; Menzies, R. G. & Clarke, J. C. (1993a), (1993b) Behaviour Research and Therapy, 31, 499-501; Menzies, R. G. & Clarke, J. C. (1995)].


Defining 'free zones': A systematic review of literature.
For decades, the notion of 'Free Zones' has remained complex and ambiguous. Despite considerable efforts in this regard, the concept of 'Free Zones' and its components have not been sufficiently explored. To further consolidate the related literature, this study conducted a literature review on the terminology of the Free Zone and its components using a systematic review method based on literature and international organizations such as the UNCTAD. This study provides needed general knowledge about the nature of Free Zones. It also presents the classifications and types of economic zones, and provides insight into what distinguishes Free Zones and economic zones from one another. Furthermore, it aggregates the Free Zone into its constituting components, concluding with insight into future research by identifying relevant challenges and gaps.


Phacoemulsification Combined With Endoscopic Versus Transscleral Cyclophotocoagulation in Poorly Controlled Glaucoma: A Comparative Case Series.
The objective of this study was to report medium-term outcomes of a novel combination of phacoemulsification with transscleral cyclophotocoagulation (phaco-TCP) compared with combined phacoemulsification and endoscopic cyclophotocoagulation (phaco-ECP) in patients with uncontrolled or suboptimally controlled glaucoma and coexisting cataract. Retrospective case series of 80 consecutive patients with a minimum of 12 months of follow-up. In total, 46 eyes underwent phaco-ECP and 34 phaco-TCP. Success was defined as intraocular pressure (IOP) between 6 and 21 mm Hg with ≥20% reduction from preoperative IOP (with no increase in ocular hypotensive medications or further glaucoma surgery). Secondary outcomes were change in IOP, number of ocular hypotensive medications and safety. The mean follow-up was 32.6 ±10.3 months. Preoperative clinical characteristics were similar in both groups. At latest follow-up, success rate was greater with phaco-TCP than phaco-ECP (67.6% and 47.8%, P=0.037). IOP was also significantly lower after phaco-TCP (14.88±5.57 mm Hg, from 22.62±6.52 mm Hg) than phaco-ECP (18.07±6.72 mm Hg, from 22.83±7.88, P=0.0273). Ocular hypotensive medications required reduced similarly after phaco-TCP (from 3.38±0.88 to 2.65±1.04 medications, P=0.0012) and phaco-ECP (from 3.07±0.929 to 2.63±1.42 medications, P=0.0108). There were no cases of hypotony or reduction in vision related to glaucoma with either surgical intervention and a similar proportion required further glaucoma surgery (phaco-ECP 15.2%, phako-TCP 5.9%, P=0.2884). Phaco-TCP appears more successful in controlling IOP than phaco-ECP with similar safety. Further investigation is warranted of this newly proposed combination which may be particularly useful where access or experience with ECP or other minimally invasive glaucoma surgery is limited.


Comparative evaluation of the Abbott RealTime High Risk HPV test and INNO-LiPA HPV Genotyping Extra test for detecting and identifying human papillomaviruses in archival tissue specimens of head and neck cancers.
The Abbott RealTime is a novel real-time PCR assay designed for concurrent individual genotyping of HPV16 and HPV18 and pooled detection of 12 HPV genotypes: HPV31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 in cervical swab specimens. In this study, the performance of RealTime for detecting HPV in formalin-fixed, paraffin-embedded tissue specimens of head and neck cancers was compared to the Innogenetics INNO-LiPA assay, which allows identification of 28 HPVs, including all 14 covered by RealTime. A total of 60 FFPE tissue specimens obtained from the same number of patients with histologically confirmed cancer of the oral cavity or oropharynx were included in the study. Following DNA extraction using a Qiagen DNA Mini Kit, RealTime and INNO-LiPA were performed on all samples, as instructed by the manufacturers. A 136-bp fragment of human beta-globin serving as an internal control in RealTime was successfully amplified from all 60 tissue samples included in the study. RealTime and INNO-LiPA showed 100% agreement and detected HPV DNA in 5/60 (8.3%) of the cancer samples, which all contained genotype HPV16. RealTime assay is a reliable, sensitive, and specific diagnostic tool for the detection and partial genotyping of targeted HPV genotypes in FFPE tissue specimens of oral and oropharyngeal cancer.


In vivo 31P NMR studies of the hepatic response to L-ethionine in anesthetized rats.
Phosphorus-31 surface coil spectroscopy has been used to study the effects of L-ethionine administration on the hepatic metabolism of the anesthetized Sprague-Dawley rat. ATP levels were found to decrease by approximately 30% 3 to 4 hr after administration of 1 mg/g body wt of L-ethionine to the anesthetized rat by gastric gavage. ATP levels returned to control values approximately 8 hr postadministration. The relatively small decrease in ATP level was confirmed by extraction and conventional enzyme assay and is a consequence of the mode of administration of the ethionine. Hepatic inorganic phosphate levels rose concomitantly with the ATP fall. There were no significant changes in either cellular pH or Mg2+ levels as monitored by the 31P shifts of sensitive metabolites. In vivo 31P NMR spectroscopy provides a promising approach to study the effects of hepatotoxicants on cellular ATP, pH, and Mg levels.


A case report of pityriasis lichenoides in a patient with chronic hepatitis C.
The authors describe a case of chronic hepatitis C associated with pityriasis lichenoides. The association and evolution during antiviral treatment of these two diseases in this patient point to a possible pathogenetic link between chronic C virus infection and pityriasis lichenoides.


UEG week 2012 report: putting endoscopy into perspective.
The 20th United European Gastroenterology Week (UEG week; 20 - 24 October 2012; Amsterdam, The Netherlands) offered, once again, the opportunity for delegates interested in gastrointestinal endoscopy to update their knowledge as colleagues from all over the world shared their experiences. Various interesting studies on endoscopic topics were presented, allowing participants to become better acquainted with recent advancements and research trends in gastrointestinal endoscopy. This report focuses on oral presentations and selected poster presentations and aims to review them in the light of recent literature.


Sonourethrography in the evaluation of urethral strictures: a preliminary report.
A total of 17 patients with suspected stricture disease underwent conventional retrograde urethrography and sonourethrography. When the length of the stricture as assessed by each imaging modality was compared to measurements at open urethroplasty in 7 patients, sonourethrography was consistently more accurate. Distension of the urethra with saline during the ultrasound examination enabled classification of the degree of spongiofibrosis, which was confirmed by full depth biopsy in 5 patients. Sonourethrography cannot adequately image the posterior urethra, even when the transcrotal approach is used. However, because it is a dynamic 3-dimensional study and can be repeated without risk of radiation exposure, sonourethrography is preferable to radiographic retrograde urography to evaluate patients with suspected anterior urethral strictures.


The effects of piroxicam to the muscosal barrier of the bladder after overdistension--an experimental study in rabbits.
The effects of piroxicam on the duration and severity of damage to the mucosal barrier of the urinary bladder after overdistension was investigated. Overdistension of the bladder was induced for 3 h in 16 New Zealand male rabbits by giving Ringer's lactate infusion (40 mL/kg/h) and furosemide (1 mg/kg) to the peritoneal cavity. Insertion of 8 Fr Foley catheter was used for obstruction of the bladder neck. In both control (C) and piroxicam (P) groups, 20 mL of 2% solution of Trypan blue in 0.9% NaCl solution was instilled into the bladder for 1 hr at 0, 24, 48 h and 7 days after overdistension. In group P daily intramuscular injection of 5 mg/kg piroxicam, and isotonic saline in group C was administrated for 7 days. Full-thickness samples were taken from the bladder at 0, 24, 48 h and 7 days after overdistension. The bladder wall was deep blue throughout in both groups at 0, 24, and 48 h. The severity and duration of inflammatory reaction was lower and nearly normalized on the 7th post procedure day in piroxicam group. Inflammatory reaction can be prevented by administration of anti-inflammatory drugs such as piroxicam but the prevention of increased permeability is unclear after overdistension of the bladder.


[OH]- negative chemical ionization mass spectrometry. Reactions of [OH]- with methadone, l-alpha-acetylmethadol and their metabolites.
The [OH]- chemical ionization spectra of methadone and three metabolites and of l-alpha-methadol and six metabolites are presented. The spectra are simple, but the methadol compounds exhibit much fragmentation. The ionization sensitivity is somewhat greater than that in CH4 positive chemical ionization.


Endoscopic examination of the colon in infancy and childhood.
Flexible fiberoptic colonoscopy is a safe and effective diagnostic procedure in infants and children. It is a sensitive and practical procedure that has made substantial contributions to the diagnosis and treatment of colonic disorders in infants and children. With further refinements in technique, future applications of its use are likely to occur.


Lectin binding properties of human follicular center lymphocytes and follicular (nodular) lymphomas.
The distribution of lectin binding receptors in normal human lymphoid tissue and follicular (nodular) lymphoma was studied in tissue sections using a panel of lectin-peroxidase and lectin-fluorescein conjugates: Concanavalin A (Con A), Peanut agglutinin (PNA), Lotus tetragonolobus agglutinin (LTA), Soybean agglutinin, Ulex europeus and Bandeiraea simplicifolia. Two lectins studied, PNA and LTA were found to bind selectively to the cell membranes of follicular centre lymphocytes in normal lymphoid tissue, and to the neoplastic cells of follicular (nodular) lymphomas. Con A, in contrast, bound selectively to follicular centre macrophages (tingible body cells) and identified in follicular (nodular) lymphomas a population of dendritic-like cells not otherwise recognized and possibly corresponding to dendritic cells identified ultrastructurally. Follicular (nodular) lymphomas share the lectin binding properties of non-neoplastic follicular centres. The expression of receptors for lectins with blood group activity (PNA T-like, LTA H-like) on follicular lymphocytes may play a role in follicle formation.


Diallyl Trisulfide Prevents Adipogenesis and Lipogenesis by Regulating the Transcriptional Activation Function of KLF15 on PPARγ to Ameliorate Obesity.
Diallyl trisulfide (DATS) is a bioactive compound in garlic. The anti-obesity effect of garlic oil has been reported, but the role and mechanism of DATS in preventing obesity remain to be explored. Studies with high-fat-diet-induced obese mice and 3T3-L1 adipocytes are performed. The results show that DATS significantly reduces lipid accumulation and repairs disordered metabolism in vivo by restraining adipogenesis and lipogenesis, and promoting lipolysis and fatty acid oxidation in white adipose tissue. In cells, DATS plays different roles at different stages of adipocyte differentiation. Notably, DATS reduces lipid accumulation mainly by inhibiting adipogenesis and lipogenesis at the late stage. KLF15 is knocked down in 3T3-L1 cells, which eliminate the inhibitory effect of DATS on adipogenesis and lipogenesis. The dual-luciferase reporter and ChIP assays indicate that DATS can inhibit the transcriptional activation function of KLF15 on PPARγ by inhibiting the binding of KLF15 to PPARγ promoter. The function comparison of structural analogs and the intervention of dithiothreitol show that disulfide bond is crucial for DATS to work. DATS prevents obesity by regulating the transcriptional activation function of KLF15 on PPARγ.


Sequestration of a dual function DNA-binding protein by Vibrio cholerae CRP.
Although the mechanism by which the cyclic AMP receptor protein (CRP) regulates global gene transcription has been intensively studied for decades, new discoveries remain to be made. Here, we report that, during rapid growth, CRP associates with both the well-conserved, dual-function DNA-binding protein peptidase A (PepA) and the cell membrane. These interactions are not present under nutrient-limited growth conditions, due to post-translational modification of three lysines on a single face of CRP. Although coincident DNA binding is rare, dissociation from CRP results in increased PepA occupancy at many chromosomal binding sites and differential regulation of hundreds of genes, including several encoding cyclic dinucleotide phosphodiesterases. We show that PepA represses biofilm formation and activates motility/chemotaxis. We propose a model in which membrane-bound CRP interferes with PepA DNA binding. Under nutrient limitation, PepA is released. Together, CRP and free PepA activate a transcriptional response that impels the bacterium to seek a more hospitable environment. This work uncovers a function for CRP in the sequestration of a regulatory protein. More broadly, it describes a paradigm of bacterial transcriptome modulation through metabolically regulated association of transcription factors with the cell membrane.


Economic valuation of a mangrove ecosystem threatened by shrimp aquaculture in Sri Lanka.
Mangrove ecosystems in Sri Lanka are increasingly under threat from development projects, especially aquaculture. An economic assessment is presented for a relatively large (42 ha) shrimp culture development proposed for the Rekawa Lagoon system in the south of Sri Lanka, which involved an extended cost-benefit analysis of the proposal and an estimate of the "total economic value" (TEV) of a mangrove ecosystem. The analysis revealed that the internal benefits of developing the shrimp farm are higher than the internal costs in the ratio of 1.5:1. However, when the wider environmental impacts are more comprehensively evaluated, the external benefits are much lower than the external costs in a ratio that ranges between 1:6 and 1:11. In areas like Rekawa, where agriculture and fisheries are widely practiced at subsistence levels, shrimp aquaculture developments have disproportionately large impacts on traditional livelihoods and social welfare. Thus, although the analysis retains considerable uncertainties, more explicit costing of the environmental services provided by mangrove ecosystems demonstrates that low intensity, but sustainable, harvesting has far greater long-term value to local stakeholders and the wider community than large shrimp aquaculture developments.


Hemispheric specificity for proprioception: Postural control of standing following right or left hemisphere damage during ankle tendon vibration.
Right brain damage (RBD) following stroke often causes significant postural instability. In standing (without vision), patients with RBD are more unstable than those with left brain damage (LBD). We hypothesised that this postural instability would relate to the cortical integration of proprioceptive afferents. The aim of this study was to use tendon vibration to investigate whether these changes were specific to the paretic or non-paretic limbs. 14 LBD, 12 RBD patients and 20 healthy subjects were included. Displacement of the Centre of Pressure (CoP) was recorded during quiet standing, then during 3 vibration conditions (80 Hz - 20s): paretic limb, non-paretic limb (left and right limbs for control subjects) and bilateral. Vibration was applied separately to the peroneal and Achilles tendons. Mean antero-posterior position of the CoP, variability and velocity were calculated before (4s), during and after (24s) vibration. For all parameters, the strongest perturbation was during Achilles vibrations. The Achilles non-paretic condition induced a larger backward displacement than the Achilles paretic condition. This condition caused specific behaviour on the velocity: the LBD group was perturbed at the onset of the vibrations, but gradually recovered their stability; the RBD group was significantly perturbed thereafter. After bilateral Achilles vibration, RBD patients required the most time to restore initial posture. The reduction in use of information from the paretic limb may be a central strategy to deal with risk-of-fall situations such as during Achilles vibration. The postural behaviour is profoundly altered by lesions of the right hemisphere when proprioception is perturbed.


Arsenate uptake by Al nanoclusters and other Al-based sorbents during water treatment.
In many parts of the world, arsenic from geogenic and anthropogenic sources deteriorates the quality of drinking water resources. Effective methods of arsenic removal include adsorption and coagulation with iron- and aluminum-based materials, of which polyaluminum chloride is widely employed as coagulant in water treatment due to its low cost and high efficiency. We compared the arsenic uptake capacity and the arsenic bonding sites of different Al-based sorbents, including Al nanoclusters, polyaluminum chloride, polyaluminum granulate, and gibbsite. Extended X-ray absorption fine structure (EXAFS) spectroscopy revealed that As(V) forms bidentate-binuclear complexes in interaction with all Al-based removal agents. The octahedral configuration of nanoclusters and the distribution of sorption sites remain the same in all types of removal agents consisting of nano-scale Al oxyhydroxide particles. The obtained distances for As(V)-O and As(V)-Al agreed with previously published data and were found to be 1.69 ± 0.02 Å and 3.17-3.21 Å, respectively. Our study suggests that As(V) binds to Al nanoclusters as strongly as to Al oxide surfaces. The As sorption capacity of Al nanoclusters was found to be very similar to that of Al clusters in a polyaluminum chloride. The most efficient Al-based sorbents for arsenic removal were Al nanoclusters, followed by polyaluminum granulate.


Organization and development of the tail bud analyzed with the quail-chick chimaera system.
After closure of the posterior neuropore, the caudal part of the embryo designated as the 'tail bud' forms a mass of undifferentiated cells from which the lumbosacral and caudal parts of the body develop. It has been proposed that the tail bud is a homogeneous structure comparable to a blastema (Holmdahl, 1925; Griffith et al., 1992). Another view is that morphogenesis of the tail bud is merely the continuation of the gastrulation process (Pasteels, 1937, 1943). In order to try to solve this controversy, we have studied the fate of definite and discrete regions of the tail bud at the 25-somite stage by using the quail-chick marker system. We found that the tail bud is composed of different domains endowed with a definite fate. A ventro-rostral region equivalent to the chordo-neural hinge defined by Pasteels gives rise to the notochord and floor plate and thus corresponds to the Hensen's node which in the tail bud pursues its rostrocaudal movement. The presumptive territory of the lateral walls of the lumbo-sacro-caudal neural tube is located caudally to the Hensen's node as it stands at the 25-somite stage. Material destined to form the sacral and caudal somites is still located in the dorsal midline in the caudalmost part of the tail bud. We thus show that the movements of invagination and divergence which characterize gastrulation are still going on in the tail bud after the 25-somite stage. Thus the somitic material located medio-dorsally diverges laterally and contributes by apposition to the growth of the trunco-caudal part of the body. The parallel between tail bud development in Amniotes and Amphibians as described recently by Gont et al. (1993) is striking and points to the unity in the development mechanisms within the Vertebrate phylum.


Reduction of pesticide application via real-time precision spraying.
Farmers focus on reducing the cost of production and aim to increase profit. The objective of this study was to quantify the reduction of pesticides applied to soybean (Glycine max (L.) Merrill) and maize (Zea mays L.) crops in several stages of the production cycle using a site-specific spraying application based on real-time sensors in the Brazilian Cerrado region. The sprayers were equipped with a precision spraying control system based on a real-time sensor. The spraying operations were performed not only for herbicide, but also for fungicide and insecticides applications. The maps recorded the percentage of the spray boom when the application was turned on (on/off spray system) with nozzle-to-nozzle control. The precision spraying system based on real-time sensors reduced the volume of pesticides (including herbicides, insecticides, and fungicides) applied to soybean and maize crops. There was a more significant reduction in the volume of pesticides applied post-emergence of the crops in the initial stages of soybean and maize when the crops had less leaf area or less foliage coverage between the rows. The cost reduction achieved using this technology was 2.3 times lower than the cost associated with pesticide application over the entire area using a conventional sprayer. Under the experimental conditions, there were no differences in the average crop yield, compared to the historical productivity of soybean and maize crops by applying this technology because the recommended doses were not affected and the site of application was limited to points where the presence of plants was present was detected.


Bone mineral density changes among women initiating blood pressure lowering drugs: a SWAN cohort study.
We examined the effect of blood pressure lowering drugs on BMD using data from the Study of Women's Health Across the Nation. Thiazide users had a slower decline in BMD compared to nonusers, while decline among ACE inhibitor and beta blocker users were similar to rates in nonusers. Several blood pressure lowering drugs may affect bone mineral density (BMD), leading to altered fracture risk. We examined the effect of blood pressure lowering drugs on BMD using data from the Study of Women's Health Across the Nation. We conducted a propensity score matched cohort study. Women were initiators of ACE inhibitors (ACEi), beta-blockers (BB), or thiazide diuretics (THZD). Their annualized BMD changes during the 14 years of observation were compared with nonusers. Among the 2312 eligible women, we found 69 ACEi, 71 BB, and 74 THZD users who were matched by a propensity score with the same number of nonusers. THZD users had a slower annual percent decline in BMD compared to nonusers at the femoral neck (FN) (-0.28% vs -0.88%; p = 0.008) and the spine (-0.74% vs -1.0%; p = 0.34), albeit not statistically significant. Annual percent changes in BMD among ACEi and BB users were similar to rates in nonusers. In comparison with BB, THZD use was associated with a trend toward less annualized BMD loss at the spine (-0.35% vs -0.60%; p = 0.08) and a similar trend at the FN (-0.39% vs -0.64%; p = 0.08); in comparisons with ACEi, THZD was also associated with less loss at the FN (-0.48% vs -0.82%; p = 0.02), but not at the spine (-0.40% vs -0.56%; p = 0.23). Neither ACEi nor BB was associated with improvements in BMD. THZD use was associated with less annualized loss of BMD compared with nonusers, as well as compared with ACEi and BB.


[Evolution of plasma concentration of gonadotropins and corticosterone during the growth of the male rat (author's transl)].
Plasma LH, FSH and corticosterone were determined between the 15th and 90th day of life, in normal male Rat. Plasma gonadotropins and corticosterone at basal conditions or after psychic aggression increased from the 15th to the 40th or 45th day of life; then all hormones decreased to adult age. The development of plasma gonadotropins and corticosterone are carried out in a parallel manner during the period studied. It was thought that perhaps the elevation of gonadotropins secretion might have stimulated the adrenals.


Effect of intrathecal dexmedetomidine on cesarean section during spinal anesthesia: a meta-analysis of randomized trials.
Intrathecal dexmedetomidine has been used in spinal anesthesia during cesarean sections. The purpose of this meta-analysis was to investigate the effect of intrathecal dexmedetomidine on the adverse reactions of spinal anesthesia during cesarean section. We searched for relevant studies using PubMed, Web of Science, and the Cochrane library. After screening studies and extracting data, we performed a meta-analysis on the effect of intrathecal dexmedetomidine during cesarean section. A total of 278 patients from 4 studies were included in this meta-analysis. The incidence of shivering in the dexmedetomidine groups was significantly lower than that in the placebo groups during cesarean section (RR=0.40, 95% CI [0.25, 0.65], P=0.0002). Intrathecal dexmedetomidine had no effect on nausea and vomiting (RR=1.08, 95% CI [0.68, 1.71], P=0.74), bradycardia (RR=1.33, 95% CI [0.31, 5.76], P=0.70), and hypotension during cesarean section (RR=0.78, 95% CI [0.59, 1.03], P=0.08). Intrathecal dexmedetomidine can effectively reduce the occurrence of shivering during cesarean section, but it does not affect the occurrence of nausea and vomiting, bradycardia or hypotension.


Removal of pharmaceutically active compounds (PhACs) and toxicological response of Cyperus alternifolius exposed to PhACs in microcosm constructed wetlands.
This study investigated the effects of selected four pharmaceutically active compounds (PhACs) (carbamazepine, sulfamethoxazole, ofloxacin, and roxithromycin) on the photosynthesis and antioxidant enzymes of Cyperus alternifolius in constructed wetlands (CWs). Moreover, the removal and kinetics of PhACs in CWs were evaluated to explore the related removal mechanisms. Results showed that C. alternifolius can uptake and withstand certain PhACs. The PhAC tolerance of C. alternifolius might be attributed to their capacity to maintain relatively normal photosynthetic activity and elevated antioxidative defense. CWs offered comparable or even higher removal efficiencies for the selected PhACs compared with conventional WWTPs. The removal of the target PhACs was enhanced in the planted CWs versus the unplanted CWs mostly because of plant uptake and rhizosphere effects. In particular, carbamazepine, which is considered the most recalcitrant of the PhACs, was significantly reduced (p<0.05). The removal of target PhACs fitted into two distinct periods. The initial fast step (within the first 2 h) was essentially attributed to the adsorption onto the CW medium surface. The subsequent slow process (2-12 h) closely followed first-order kinetics probably because of the interaction between microorganisms and plants. The obtained results indicate that C. alternifolius can phytoremediate PhAC-contaminated waters in CWs.


Recurring oral giant cell lesion in a child with X-linked hypophosphatemic rickets: clinical manifestation of occult parathyroidism?
A 9-year-old boy with X-linked hypophosphatemic rickets had a recurring oral giant cell lesion. These lesions are relatively uncommon in children and represent a potentially aggressive disorder that is microscopically indistinguishable from the brown tumors of hyperparathyroidism. Subclinical hyperparathyroidism is not uncommon in X-linked hypophosphatemic rickets and may account for the giant cell lesion in this patient.


Validity, reliability, and feasibility of a quality of life questionnaire for people with dementia.
The present study investigates the validity, reliability, and applicability of the German version of the QUALIDEM, which is used to measure the quality of life of people with dementia in nursing homes. The sample consists of data from 203 people (average age 84 ± 9 years, 74% female) with mild to moderate dementia and 283 persons (average age 86 ± 8 years, 79% female) with severe to very severe dementia. These are baseline data from two lighthouse projects on dementia (STI-D and InDemA). The investigation of the feasibility is based on four expert interviews. The construct validity of the 37-item version of the QUALIDEM shown by the factors satisfied behavior, unapproachable and unsatisfied behavior, positive self-image, negative affect, social relations, feeling at home, restless tense behavior, and having something to do were identified. Furthermore, for the 18-item version the following four factors were computed: satisfied behavior, unapproachable and unsatisfied behavior, restless tense behavior, and negative affect. Cronbach's α values for the determined factors are between 0.64 and 0.87 (37-item version) and between 0.61 and 0.83 (18-item version), which corresponds with a medium to high reliability (internal consistency). Furthermore, the student assistants assessed the QUALIDEM as applicable and practical.


Hypertension in postmenopausal Indonesian Women: fluctuating Body Mass Index as a potential predictor of decreasing blood pressure.
The burden of Hypertension (HT) [P1][YT2] in Indonesian postmenopausal women has increased over the past years. Obesity is the most prevalent risk of HT among postmenopausal women. This study evaluates the relationship of fluctuating BMI with BP in postmenopausal women in Bogor, Indonesia. This longitudinal study acquired secondary data from a previous study of the "Cohort Study of NCD' Risk Factors" along with a two-year follow-up. Data were analyzed from a total of 888 postmenopausal women aged ≥ 25 years[P3][wr4]. BMI and BP fluctuations were calculated from baseline BMI at the first visit (T1) until the observation period (T7). The significance of panel analysis at p value < 0.05.[P5][wr6]. The fixed-effect model showed a significant correlation between BMI changes with the changes in SBP and DBP and fluctuating BMI with SBP. After adjustment for physical activity, 1 kg of weight gain will increase SBP and DBP in normotensive, controlled, and uncontrolled hypertensive individuals. After adjusting for smoking, BMI reduction by 1% would lower the SBP as much as 2-3 mmHg compared to a stable BMI. Fluctuating BMI was a predictor in decreasing BP in postmenopausal women, so it could be used to control HT.


Postchemotherapy retroperitoneal lymph node dissection in advanced testicular cancer: radical or modified template resection.
The anatomical extent of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) has been discussed controversially for many years. To evaluate the necessity of PC-RPLND with modified or radical template resection in patients with advanced nonseminomatous germ-cell tumors (NSGCT) and residual masses following systemic chemotherapy. The charts of 152 consecutive patients who were treated at two tertiary referral centers were retrospectively reviewed. All patients underwent PC-RPLND, with 54 and 98 patients undergoing a radical template resection and 98 patients undergoing a modified template resection. Modified template resection was performed if the location of the residual mass corresponded to the primary landing zone of testis cancer and the residual mass measured < or = 5 cm in diameter. In all other cases a full bilateral PC-RPLND was chosen. The following data were analyzed: location of the residual mass, extent of surgery, length of surgery, treatment-associated complications, nerve-sparing approach, adjunctive surgical procedures, postoperative morbidity, duration of hospital stay, early and late complications, relapse rates, cancer-specific survival rates, and overall survival rates. Overall, 84 patients (55.2%) had necrosis/fibrosis, 45 (29.6%) had mature teratoma, and 23 (15.1%) had vital cancer in the surgical specimens. Antegrade ejaculation was preserved in 85% and 25% of patients undergoing modified and bilateral PC-RPLND (p=0.02), respectively. Eight recurrences (5.2%) were observed after a mean follow-up of 39 mo (range 6-105 mo): one patient had an in-field relapse following modified PC-RPLND, and seven patients had recurrences outside the boundaries of full bilateral PC-RPLNDs. The 2-yr disease-free survival rates were 78.6% and 92.8% for bilateral and modified PC-RPLND, respectively. The limitations of this study were a short follow-up, a limited number of patients, and the retrospective nature of the study. Full bilateral PC-RPLND is the standard approach to extensive residual masses. In well-defined masses a modified template PC-RPLND does not interfere with oncologic outcome but decreases treatment-associated morbidity.


Short hospital stay augmented with education and home-based rehabilitation improves function and quality of life after hip replacement: randomized study of 50 patients with 6 months of follow-up.
Because of current cost restrictions, we studied the effect of a shorter hospital stay on function, pain and quality of life (QOL) after total hip replacement (THR). 50 patients from two hospitals were randomized into a study group (SG) of 27 patients receiving preoperative and postoperative education programs, as well as home visits from an outpatient team, and a control group (CG) of 23 patients receiving "conventional" rehabilitation often augmented by a stay at a rehabilitation center. Mean hospital stay was shorter for the SG than for the CG (6.4 days and 10 days, respectively; p < 0.001). During the 6-month study period, there were 9 non-fatal complications in the SG and 12 in the CG (p = 0.3). The difference in Oxford Hip Score between the groups was not statistically significant before the operation, but was better for the SG at 2 months (p = 0.03) and this difference remained more or less constant throughout the study. The overall score from the Nottingham Health Profile indicated a better QOL in the SG. Our preoperative education program, followed by postoperative home-based rehabilitation, appears to be safer and more effective in improving function and QOL after THR than conventional treatment.


Integrated miRNA and mRNA expression profiling identifies novel targets and pathological mechanisms in autoimmune thyroid diseases.
The mechanisms underlying autoimmune thyroid disease (AITD) remain elusive. Identification of such mechanisms would reveal novel and/or better therapeutic targets. Here, we use integrated analysis of miRNAs and mRNAs expression profiling to identify potential therapeutic targets involved in the mechanisms underlying AITD. miRNA and mRNA from twenty fresh-frozen thyroid tissues (15 from AITD patients and 5 from healthy controls) were subjected to next-generation sequencing. An anti-correlated method revealed potential pathways and disease targets, including proteins involved in the formation of primary cilia. Thus, we examined the distribution and length of primary cilia in thyroid tissues from AITD and controls using immunofluorescence and scanning electron microscopy, and parsed cilia formation in thyroid cell lines in response to inflammatory stimuli in the presence of miRNA mimics. We found that the expression of miR-21-5p, miR-146b-3p, miR-5571-3p and miR-6503-3p was anti-correlated with Enolase 4 (ENO4), in-turned planar cell polarity protein (INTU), kinesin family member 27 (KIF27), parkin co-regulated (PACRG) and serine/threonine kinase 36 (STK36) genes. Functional classification of these miRNA/mRNAs revealed that their differential expression was associated with cilia organization. We demonstrated that the number and length of primary cilia in thyroid tissues was significantly lower in AITD than in control (frequency of follicular ciliated cells in controls = 67.54% vs a mean of 22.74% and 21.61% in HT and GD respectively p = 0.0001, by one-way ANOVA test). In addition, pro-inflammatory cytokines (IFNγ and TNFα) and specific miRNA mimics for the newly identified target genes affected cilia appearance in thyroid cell lines. Integrated miRNA/gene expression analysis has identified abnormal ciliogenesis as a novel susceptibility pathway that is involved in the pathogenesis of AITD. These results reflect that ciliogenesis plays a relevant role in AITD, and opens research pathways to design therapeutic targets in AITD. Instituto de Salud Carlos III, Comunidad de Madrid, Grupo Español de Tumores Neuroendocrinos y Endocrinos, Ministerio de Economía y Empresa and FEDER.


Signaling in electrical networks of the Venus flytrap (Dionaea muscipula Ellis).
The Venus flytrap captures insects with one of the most rapid movements in the plant kingdom. There is a significant difference between properties of electrical signals generated in the Venus flytrap described in literature. Amplitudes of action potentials vary from 14 mV to 200 mV with duration of signals from 2 ms to 10 s. Here we present experimental study of potential differences between Ag/AgCl electrodes inserted to the trap, petiole, and into soil or external ECG electrodes attached to surfaces of the Venus flytrap. Diverse types of electrodes with various positions in a plant tissue or in soil show different amplitude and duration of electrical signals because potentials are measured in different electrochemical circuits. Electrical signals in the Venus flytrap were induced by mechanical stimulation of the trigger hairs or by chemical stimulation of a midrib using small drops of H2O2 or HNO3. Here we found that action potentials can propagate with speed up to 10 m/s in the trap of D. muscipula. Results are compared with equivalent electrical circuits.


Rel B-modified dendritic cells possess tolerogenic phenotype and functions on lupus splenic lymphocytes in vitro.
Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by high morbidity and mortality and its treatment remains challenging. Dendritic cells (DCs) have been shown to participate in the initiation and perpetuation of lupus pathogenesis and the DCs that can induce tolerogenicity appear as potential cell-based therapy in this condition. In this study, we examined the in vitro tolerogenic properties of bone-marrow derived DCs (BMDCs) in the murine lupus setting. We used lentiviral transduction of RelB-silencing short hairpin RNA to modify the expression of RelB, a key transcription factor regulating DC maturation, in BMDCs from MRL/MpJ mice. Tolerogenic properties of RelB-modified DCs were compared with scrambled control (SC) -modified DCs. RelB expression was found to be significantly reduced in RelB-modified DCs derived from MRL/MpJ mice, wild-type of the same genetic background as MRL/lpr lupus-prone mice. These MRL/MpJ RelB-modified DCs displayed semi-mature phenotype with expression of lower levels of co-stimulatory molecules compared with SC-modified DCs. RelB-modified DCs were found to be low producers of interleukin-12p70 (IL-12p70) and could induce hyporesponsiveness of splenic T cells from MRL/MpJ and MRL/lpr mice. Furthermore, they down-regulated interferon-γ expression and induced IL-10-producing T cells in MRL/MpJ splenocytes, and attenuated interferon-γ and IL-17 expression in MRL/lpr splenic CD4(+) lymphocytes. Splenocytes primed by RelB-modified DCs demonstrated antigen-specific suppressive effects on allogeneic splenocytes. In conclusion, RelB-silencing in DCs generates DCs of tolerogenic properties with immunomodulatory function and appears as potential option of cell-targeted therapy.


Clinical outcomes of neoadjuvant chemotherapy for resectable colorectal liver metastasis with intermediate risk of postoperative recurrence: A multi-institutional retrospective study.
Risk-scoring systems for colorectal liver metastasis (CRLM) after hepatectomy allow prognoses to be predicted preoperatively. We investigated the clinical outcomes of neoadjuvant chemotherapy for resectable CRLM according to patient risk status, aiming to determine the subgroup of patients who could benefit from neoadjuvant chemotherapy. In this multi-institutional retrospective analysis, the preoperative risk score was calculated from six previously reported factors: synchronous metastases, primary lymph node positivity, tumor number, largest tumor diameter, extrahepatic metastasis, and the preoperative carbohydrate antigen 19-9 level. Patients were divided into three groups according to their risk scores: low risk (score = 0), intermediate risk (score 1-10), and high risk (score ≥11). Overall and recurrence-free survival curves were calculated using the Kaplan-Meier method. After propensity-score matching in the intermediate-risk group, we compared clinicopathological features and outcomes. There were 318 cases, from 20 institutions. The preoperative risk score could be calculated in 277 cases. There were 34, 192, and 51 patients in the low-, intermediate-, and high-risk groups, respectively. Intermediate-risk group patients who received neoadjuvant chemotherapy had significantly better recurrence-free survival than that of patients without neoadjuvant chemotherapy (P = .0453). After propensity-score matching in the intermediate-risk group, the recurrence-free survival rate was better in patients who received neoadjuvant chemotherapy (P = .0261). But the overall survival rate was not improved after the matching. Neoadjuvant chemotherapy for resectable CRLM might prolong the recurrence-free survival period for intermediate-risk patients with preoperative risk scores in the range of 1-10, but the overall survival was not improved by neoadjuvant chemotherapy.


Prospective marriage and divorce data on Norwegian cohorts of two-sex marriages from 1886 until 2018.
The article contains prospective data on all two-sex marriages formed in Norway between 1886 and 2018, with annual follow-up for 60 years, totaling 133 cohorts and 2 698 632 marriages. The data list the number of marriages that ended in divorce throughout each year of follow-up. The data were obtained through a special order from Statistics Norway. The data from 1981 to 2018 contain additional information about male and female ages, the number of divorces from each cohort in the total population of marriages, as well as divorces among marriages formed in urban and rural areas of the country under four marriage and remarriage constellations: first time for both spouses, first time for one and second time for the other, second time for both, and third time or more for at least one in the couple. Marriages formed within a calendar year are pooled into cohorts, and each pair was examined annually to ensure that the same two persons remained married.


Diffuse peripheral odontogenic fibroma with concomitant plasma cell gingivitis--a case report and literature review.
Peripheral odontogenic fibroma is a rare odontogenic neoplasm that occurs on the gingiva, and cases of diffuse gingival involvement are most uncommon. An example of such a case compounded by superimposed plasma cell gingivtis is presented together wth a review of the literature.


The expert witness in medical malpractice litigation: through the looking glass.
Neurologists have professional, ethical, and social obligations to ensure that expert witness testimony is reliable, objective, and truthful. In the past, an absence of professional regulatory oversight combined with immunity from civil litigation allowed the partisan expert to flourish. This is no longer the case. The expert witness unquestionably faces an increasingly perilous liability climate, and must be cognizant of the legal rules and procedures. The authors provide guidelines with risk management strategies for the neurologist serving as an expert witness.


MiR-125 family improves the radiosensitivity of head and neck squamous cell carcinoma.
MiRNAs can affect the radiosensitization of head and neck squamous cell carcinoma (HNSCC). We aimed to analyze the function of miR-125 family members in HNSCC using The Cancer Genome Atlas (TCGA) and determine their effect on radiation in laryngeal squamous cell cancer (LSCC). First, we systematically analyzed the role of the miR-125 family in HNSCC using the TCGA database and found that miR-125a-5p is associated with radiotherapy. We then performed comprehensive enrichment analysis of miR-125a-5p and predicted target genes. Then, we performed transfection, cell proliferation assays, reverse transcription polymerase chain reaction, apoptosis assays, micronucleus tests, and western blotting on hep-2 cells selected with puromycin. MiR-125 family members exhibited significantly different expression in HNSCC. They were significantly associated with tumor-node-metastasis staging, clinical stages, and histological grades. Radiation therapy had a statistically effect on miR-125 family members, except miR-125a-3p. Moreover, miR-125a-5p was related to overall survival in LSCC. Thus, we predicted 110 target genes and seven hub genes of miR-125a-5p. The proliferation rate of cells transfected with lentivirus vector expressing miR-125a-5p was significantly reduced compared to the other groups. The radiation effect was enhanced in cells transfected with miR-125a-5p. The ratio of apoptotic cells transfected and exposed to X-rays (10 Gy) was distinctly higher than that of the Ad-control group. Western blotting analysis revealed that miR-125a-5p upregulated the apoptotic regulators P53 and rH2AX. Thus, miR-125a-5p may increase radiosensitivity in LSCC via upregulation of pro-apoptotic genes. MiR-125 family members could be prognostic biomarkers of HNSCC and improve HNSCC sensitivity to radiotherapy by activating P53. Upregulating miR-125a-5p via lentivirus vectors may be a novel strategy to strengthen the effect of radiotherapy on LSCC.


Analysis of antibodies to neuronal surface antigens in adult opsoclonus-myoclonus.
Antibodies against neuronal surface antigens (NSA-ab) have been described in pediatric opsoclonus-myoclonus syndrome (OMS). We analyzed the presence of NSA-ab by flow cytometry and immunocytochemistry of live cerebellar granular neurons (CGN) in the serum of 25 adult patients with idiopathic (14) and paraneoplastic (11) OMS. Paraneoplastic, but not idiopathic, OMS sera showed a CGN surface binding by flow cytometry higher than that of controls (mean MFI (median fluorescence intensity): 29+/-6.9 vs. 20+/-5.8; p=0.001) but only one serum had a binding greater than three standard deviations of controls. OMS sera did not label live CGN by immunocytochemistry. Unlike pediatric OMS, NSA-ab were not detected in adult cases suggesting that the immunity to NSA in OMS is heterogeneous.


TGF-beta 1-induced inhibition of mouse mammary ductal growth: developmental specificity and characterization.
TGF-beta 1, implanted into growing mouse mammary glands, was previously shown to inhibit ductal growth in an apparently normal and fully reversible manner. In this report we extend these findings to show that TGF-beta 1 inhibition is highly specific. In pregnant or hormone-treated mice, doses of TGF-beta 1 that were capable of fully inhibiting ductal elongation had little effect on the proliferation of lobuloalveolar structures. Additionally, the inhibitory action of TGF-beta 1 on ducts is epithelium-specific, resulting in cessation of DNA synthesis in the rapidly proliferating epithelium of mammary end buds, but does not inhibit DNA synthesis in the stroma surrounding the end buds. At the cellular level, transplant studies showed that TGF-beta 1 inhibited the regeneration of mammary ductal cells when implanted into mammary gland-free fat pads by suppressing the formation of new end buds, without inhibiting maintenance DNA synthesis in ductal lumenal epithelium; this observation indicates the potential of TGF-beta 1 to maintain patterning by suppressing adventitious lateral branching. The time-course of TGF-beta 1 inhibition of end buds was rapid, with cessation of DNA synthesis by 12 hr, followed by loss of the stem cell (cap cell) layer. The question of glandular exposure to TGF-beta 1 administered in EVAc implants was also investigated. Incorporation of TGF-beta 1 into EVAc was found not to degrade the hormone, while the release kinetics of the ligand from implants, its retention in the gland, and the demonstrable zone of exposure were consistent with observed inhibitory effects. These results support the hypothesis that TGF-beta 1 is a natural regulator of mammary ductal growth.


Calcinated MIL-100(Fe) as a CO2 adsorbent to promote biomass productivity of Arthrospira platensis cells.
In order to solve the problems of short residence time and low diffusion of CO2 gas in microalgal solution, calcinated metal-organic framework MIL-100(Fe) were first used as CO2 adsorbents to promote the growth of Arthrospira platensis cells by increasing carbon fixation. The adsorbent (MIL-100(Fe)-4 h) containing unsaturated metal sites, improved the conversion of CO2 to dissolved inorganic carbon by 52.3% and concentration of HCO3- by 20.0% in culture medium, as compared to the medium without CO2 adsorbent added. The increased HCO3- concentration facilitated carboxysome accumulation (increased to 21.7 times) to activate the photosynthetic Calvin cycle in Arthrospira cells. The increased cell growth rate promoted cell volume by 132% and knot length by 102%, while the fractal dimension of the cell surface decreased by 13.5%. The biomass productivity of Arthrospira cells cultivated with the CO2 adsorbent MIL-100(Fe)-4 h remarkably increased by 81.9%.


Trans Fatty Acids Suppress TNF-α-Induced Inflammatory Gene Expression in Endothelial (HUVEC) and Hepatocellular Carcinoma (HepG2) Cells.
Trans fatty acids (TFA) intake has been linked to cardiovascular diseases and liver diseases; yet the effect of TFA on inflammation remains controversial. Accordingly, the objective of this paper was to determine the in vitro effects of TFA on inflammatory gene expression. Human umbilical vein endothelial cells (HUVEC) and human hepatocellular carcinoma (HepG2) cells were treated for 24 h with either trans-vaccenic acid (tVA), trans-palmitoleic acid (tPA) or elaidic acid (EA) at concentrations of 5-150 µM, or with a mixture of tVA and tPA (150/50 µM). All TFA were highly incorporated into cell membranes, as determined by gas chromatography, representing 15-20% of total fatty acids in HUVEC and 3-8% in HepG2 cells. Incorporation of EA, a common industrial TFA, increased the ratio of the stearoyl-CoA desaturase (SCD-1), a key enzyme involved in fatty acid metabolism. Ruminant TFA, including tVA, tPA and the mixture of tVA and tPA, significantly reduced the TNF-α-induced gene expression of TNF, VCAM-1 and SOD2 in HUVEC, as well as TNF and IL-8 in HepG2 cells. EA also decreased inflammatory gene expression in HUVEC, but not in HepG2 cells. The inhibition of peroxisome proliferator-activated receptor (PPAR)-γ did not influence the effects of TFA on gene expression. Overall, physiological and supraphysiological concentrations of TFA, especially tVA and tPA, prevented inflammatory gene expression in vitro. This effect is independent of PPAR-γ activation and may be due to an alteration of fatty acid metabolism in cell membranes caused by the high incorporation of TFA.


[Diagnosis of glutaric acidemia type ⅡC by fetal whole exome sequencing].
To explore the genetic basis of a fetus with enlargement and enhanced echo of the kidneys. The imaging data of the fetus were collected, in addition with 20 mL amniotic fluid sample and 2 mL peripheral blood samples of both parents. Amniotic DNA was extracted for library construction and whole exome sequencing, and Sanger sequencing was carried out to verify candidate variant associated with the fetal phenotype. Prenatal ultrasound showed that the fetus had enlargement and enhanced echo of the kidneys, in addition with many small renal cysts. Whole exome sequencing showed that the fetus carried pathogenic compound heterozygous variants of the ETFDH gene, namely c.3G>C and c.1436dupA. Sanger sequencing of the family suggested that the variants were inherited from its mother and father, respectively. By combining its clinical manifestations and results of whole exome sequencing, the fetus was diagnosed as glutaric acidemia type ⅡC due to the compound heterozygous variants of the ETFDH gene. Above results have provided a basis for prenatal diagnosis and genetic counseling. Fetal exome sequencing has provided an important tool for prenatal diagnosis.


Slipped capital femoral epiphysis during treatment with recombinant human growth hormone for Turner syndrome.
Recombinant human growth hormone has recently been used to treat the short stature of Turner syndrome. However, this therapy may induce slipped capital femoral epiphysis, since the epiphyseal plate widens and becomes weak through either growth hormone or hypogonadism. This report shows that a slipped capital femoral epiphysis occurred during this treatment for an 11-year-old girl who was suffering from Turner syndrome. Thus, these patients who are being treated with growth hormone should be carefully observed.


Infective endocarditis risk in patients with bicuspid aortic valve: Systematic review and meta-analysis.
Antibiotic prophylaxis in bicuspid aortic valve patients is currently a matter of debate. Although it is no longer recommended by international guidelines, some studies indicate a high risk of infective endocarditis. We aim to evaluate the risk of native valve infective endocarditis in bicuspid aortic valve patients and compare to individuals with tricuspid aortic valve. Study search of longitudinal studies regarding infective endocarditis incidence in bicuspid aortic valve patients (compared with tricuspid aortic valve/overall population) was conducted through OVID in the following electronic databases: MEDLINE, CENTRAL, EMBASE; from inception until October 2020. The outcomes of interest were the incidence rate and relative risk of infective endocarditis. The relative risk and incidence rate (number of cases for each 10 000 persons-year) with their 95 % confidence intervals (95 %CI) were estimated using a random effects model meta-analysis. The study protocol was registered at PROSPERO CRD42020218639. Eight cohort studies were selected, with a total of 5351 bicuspid aortic valve patients. During follow up, 184 bicuspid aortic valve patients presented infective endocarditis, with an incidence rate of 48.13 per 10,000 patients-year (95 %CI 22.24-74.02), and a 12-fold (RR: 12.03, 95 %CI 5.45-26.54) increased risk compared with general population, after adjusted estimates. This systematic review and meta-analysis suggests that bicuspid aortic valve patients have a significant high risk of native valve infective endocarditis. Large prospective high-quality studies are required to estimate more accurately the incidence of infective endocarditis, the relative risk and the potential benefit of antibiotic prophylaxis.


Effect of R-(-)-deprenyl and harmaline on dopamine- and peroxynitrite-induced membrane permeability transition in brain mitochondria.
The present study examined the effect of MAO inhibitors, deprenyl and harmaline, on the membrane permeability transition in brain mitochondria. Deprenyl, harmaline, and antioxidant enzymes (SOD and catalase) attenuated alteration of the swelling, membrane potential, cytochrome c release, and Ca2+ transport in mitochondria treated with dopamine. In contrast, deprenyl and harmaline did not reduce the peroxynitrite-induced change in membrane permeability. Deprenyl and harmaline inhibited the decrease in thioredoxin reductase activity and the thiol oxidation in mitochondria treated with dopamine but did not decrease the effect of peroxynitrite. Deprenyl and harmaline significantly decreased the formation of melanin from dopamine. The results suggest that deprenyl and harmaline may protect brain mitochondria against the toxic action of dopamine oxidation by the maintenance of thioredoxin reductase activity, inhibition of thiol oxidation, and inhibition of dopamine oxidation product formation. In contrast, MAO inhibitors may not defend brain mitochondria against damaging action of peroxynitrite.


Studies on polypeptides. XXVI. Synthesis of the N-terminal 1--23 peptide sequence of rat pancreatic ribonuclease; enzymatic activity of the hybrid complex with bovine S-protein.
A description is given of the synthesis by fragment condensation of the peptide Gly-Glu-Ser-Arg-Glu-Ser-Ser-Ala-Asp-Lys-Phe-Lys-Arg-Gln-His-Met-Asp-Thr-Glu-Gly-Pro-Ser-Lys corresponding to the 1--23 amino acid sequence of rat pancreatic ribonuclease. This rat peptide combined with bovine S-protein yields a fully active ribonuclease S' analogue.


Detection and genetic characterization of feline kobuviruses.
In order to survey for feline kobuviruses infection, fecal samples (n = 39) of cats with diarrhea were collected during 2011-2012. Six (14.5%) of the fecal samples tested were positive for feline kobuviruses. The partial nucleotide sequences of feline kobuviruses based on the RNA-dependent RNA polymerase gene were compared to those of other species. Feline kobuviruses were most closely related to canine kobuvirus in terms of their amino acid and nucleotide levels. In a phylogenetic tree, feline kobuviruses were also closely clustered with canine kobuvirus, Aichi virus (human), and mouse kobuvirus. This is the first report of the detection and genetic characterization of feline kobuviruses.


Meditation Based Lifestyle Modification (MBLM) in outpatients with mild to moderate depression: A mixed-methods feasibility study.
Integrative mental health care can be applied to treat depression with a person-centered, lifestyle-modifying, and more salutogenic approach to mental health and human flourishing. In this article, we report on the feasibility and acceptability of a new mind-body program, Meditation Based Lifestyle Modification (MBLM), in outpatients with mild or moderate depression. This is a single-arm mixed-methods feasibility study of n = 25 outpatients in psychiatric care. Depressive symptoms, scores for mindfulness, aspects of spirituality, and eudaemonic well-being based on yoga philosophy were assessed at baseline and at the end of the intervention. Adherence was monitored and face-to-face interviews were held after the program to explore the acceptability and feasibility of MBLM. Twenty patients (75 %) completed at least six sessions of the course. Adherence was 87.5 % of allocated sessions. In qualitative analysis, more than half of the participants experienced novelty and inspiration through practicing the ethical aspects of yoga (e.g., nonviolence, truthfulness, etc.). Almost all participants experienced a decrease in emotional distress. Virtually all participants reported more self-confidence and self-acceptance. In quantitative analysis, participants reported a clinically important decrease in depressive symptoms of 39.23 % (p = .002), eudaemonic well-being increased significantly in a range of related scales and scores for mindfulness increased (p < .001). MBLM is a highly acceptable and feasible program for outpatients with mild to moderate depression. This comprehensive, lifestyle-modifying approach is highly relevant to preventing and treating mental illness, and treating psychic comorbidities in patients with chronic somatic illness.


Beta-amyloid regulation of presynaptic nicotinic receptors in rat hippocampus and neocortex.
Alteration by beta-amyloid (Abeta) of signaling via nicotinic acetylcholine receptors (nAChRs) has been implicated in the early stages of Alzheimer's disease. nAChRs function both post- and presynaptically in the nervous system; however, little is known about the functional consequence of the interaction of Abeta with these receptors, particularly those on presynaptic nerve terminals. In view of the strong correlation between loss of synaptic terminals and dementia, together with the reduction in nAChRs in Alzheimer's disease, the possibility exists that presynaptic nAChRs may be targets for Abeta. To explore this possibility, we assessed the effect of Abeta peptides on nicotine-evoked changes in presynaptic Ca2+ level via confocal imaging of isolated presynaptic nerve endings from rat hippocampus and neocortex. Abeta1-42 appeared to inhibit presynaptic nAChR activation by nicotine. Surprisingly, picomolar Abeta1-42 was found to directly evoke sustained increases in presynaptic Ca2+ via nAChRs, revealing that the apparent inhibitory action of Abeta1-42 was the result of an occlusion of nicotine to further stimulate the receptors. The direct effect of Abeta was found to be sensitive to alpha-bungarotoxin, mecamylamine, and dihydro-beta-erythroidine, indicating involvement of alpha7-containing nAChRs and non-alpha7-containing nAChRs. Prior depolarization strongly attenuated subsequent Abeta-evoked responses in a manner dependent on the amplitude of the initial presynaptic Ca2+ increase, suggesting that nerve activity or Ca2+ channel density may control the impact of Abeta on presynaptic nerve terminal function. Together, these results suggest that the sustained increases in presynaptic Ca2+ evoked by Abeta may underlie disruptions in neuronal signaling via nAChRs in the early stages of Alzheimer's disease.


Physiological regulation of Syntrichia caninervis Mitt. in different microhabitats during periods of snow in the Gurbantünggüt Desert, northwestern China.
Moss crusts, the most advanced stage of biological soil crust (BSC) development, play important roles in BSC biomass and soil surface stabilization. They usually survive freeze-thaw cycles and remain active during periods of extremely low temperatures. We selected Syntrichia caninervis Mitt., the dominant moss crust species, to study physiological characteristics in winter in three different microhabitats (under the canopy of living shrubs, under dead shrubs, and in exposed areas) in the Gurbantünggüt Desert of northwestern China. The results show that soluble sugar content and antioxidant enzyme activity were significantly higher when heavy snow covered the ground in midwinter, than in early winter and late winter. Soluble protein content was highest in mosses in BSCs under shrub canopies. In contrast, antioxidant enzyme activity was at its maximum in BSCs of exposed areas. Our results indicate that moss crusts have the potential to effectively survive rapid environmental change during winter by an increase in osmoregulatory substances and by increased antioxidant enzymes activity. Mosses in BSCs in exposed areas showed the highest antioxidant enzyme activity, in direct contrast to that of mosses in BSCs growing under canopies of both dead and living shrubs. This may indicate that plants of S. caninervis growing in exposed conditions are better adapted to harsh environmental conditions than plants growing in more sheltered habitats.


Acute pulmonary complications in the setting of high risk gestational trophoblastic neoplasia and induction of chemotherapy.
Gestational trophoblastic neoplasia (GTN) consists of rare malignancies of the placenta with a known propensity to metastasize to the lungs. GTN is treated with chemotherapeutic agents known to cause lung injury, further placing patients at risk for serious pulmonary events. In the literature, only a few reports of these complications and their management have been described. Here, we present two cases of GTN with pulmonary complications in the hopes of providing guidance in management. Management of these acute complications had to be balanced between continuation of life-saving therapy to reduce disease burden versus further exacerbation existing pulmonary disease. A review of the English language literature on pulmonary complications in GTN and chemotherapy was performed. In these two cases, we identified key steps that were critical in management: inpatient chemotherapy, early intervention and transfer to an intensive unit when needed, multidisciplinary teams, and altering regimens to reduce lung toxicity. Sequelae of pulmonary injury secondary to chemotherapy can be similar to those secondary to metastases. Because consistent criteria for chemotherapy-induced lung injury has not been established, the true incidence of lung injury that is directly related to chemotherapy versus metastatic disease cannot always be parsed out, making management of these complications difficult. There is also a lack of centralized care for a rare disease like GTN and regional differences in incidence, which can lead to inconsistent treatment decisions. It therefore remains important to illuminate rarely seen complications and their management in the hopes of providing guidance to future clinicians.


Improved gas chromatographic analysis of chlorpromazine in blood serum.
Reliable determinations of chlorpromazine levels in blood serum samples obtained from patients were accomplished by electron capture gas chromatography. By using modifications of the procedure to insure stability of the sample, minimal losses during sample preparation and gas chromatography, and by selecting appropriate operating parameters of the electron capture detector, excellent agreement was obtained in replicate analyses with a limit of sensitivity of 1 ng/ml in 1 ml of plasma.


Effects of essential oils on ruminal microorganisms and their protein metabolism.
A commercial blend of essential oil (EO) compounds was added to a grass, maize silage, and concentrate diet fed to dairy cattle in order to determine their influence on protein metabolism by ruminal microorganisms. EO inhibited (P < 0.05) the rate of deamination of amino acids. Pure-culture studies indicated that the species most sensitive to EO were ammonia-hyperproducing bacteria and anaerobic fungi.


Genotyping and antifungal susceptibility of human subgingival Candida albicans isolates.
Subgingival colonization by Candida albicans has been described in human immunodeficiency virus (HIV)-infected individuals, but subgingival isolates have scarcely been characterized, particularly with respect to genotype and antifungal susceptibility. A series of 29 subgingival strains of C. albicans isolated from nine HIV-infected individuals was typed by electrophoretic karyotyping and tested for susceptibility to fluconazole, itraconazole, the new investigational triazole posaconazole and amphotericin B. DNA typing showed genetic heterogeneity within subgingival isolates, as almost every individual harbored his/her own specific isolate. Genetic identity was usually demonstrated within oral and subgingival isolates simultaneously collected from the same individual, but a number of DNA types were found to be unique to subgingival strains. These findings suggest that colonization is not just the result of Candida spreading from oral surfaces, and that subgingivally adapted strains could be involved. All isolates were susceptible to all the triazole drugs tested and amphotericin B. Additional studies on subgingival Candida colonization and further characterization of subgingival isolates are now required to clarify the role of Candida as opportunistic periodontal pathogen.


How do barley plants with impaired photosynthetic light acclimation survive under high-light stress?
WHIRLY1 deficient barley plants surviving growth at high irradiance displayed increased non-radiative energy dissipation, enhanced contents of zeaxanthin and the flavonoid lutonarin, but no changes in α-tocopherol nor glutathione. Plants are able to acclimate to environmental conditions to optimize their functions. With the exception of obligate shade plants, they can adjust their photosynthetic apparatus and the morphology and anatomy of their leaves to irradiance. Barley (Hordeum vulgare L., cv. Golden Promise) plants with reduced abundance of the protein WHIRLY1 were recently shown to be unable to acclimatise important components of the photosynthetic apparatus to high light. Nevertheless, these plants did not show symptoms of photoinhibition. High-light (HL) grown WHIRLY1 knockdown plants showed clear signs of exposure to excessive irradiance such as a low epoxidation state of the violaxanthin cycle pigments and an early light saturation of electron transport. These responses were underlined by a very large xanthophyll cycle pool size and by an increased number of plastoglobules. Whereas zeaxanthin increased with HL stress, α-tocopherol, which is another lipophilic antioxidant, showed no response to excessive light. Also the content of the hydrophilic antioxidant glutathione showed no increase in W1 plants as compared to the wild type, whereas the flavone lutonarin was induced in W1 plants. HPLC analysis of removed epidermal tissue indicated that the largest part of lutonarin was presumably located in the mesophyll. Since lutonarin is a better antioxidant than saponarin, the major flavone present in barley leaves, it is concluded that lutonarin accumulated as a response to oxidative stress. It is also concluded that zeaxanthin and lutonarin may have served as antioxidants in the WHIRLY1 knockdown plants, contributing to their survival in HL despite their restricted HL acclimation.


Fine needle aspiration cytology of thyroid nodules: conventional vs thin layer technique.
Liquid-based cytology using the thin layer technique has recently been introduced in thyroid fine needle aspiration cytology together with or in substitution of direct smears, but its usefulness is still controversial and relatively few studies have been published in this field. The aim of the present study was to compare the results obtained from conventional smears with those from thin layer smears. In 3875 thyroid nodules, a double cytologic sampling was taken in randomized order, to prepare conventional or thin layer smears. The diagnoses agreed in 2934 (75.7%) cases and disagreed in 941 (24.3%). The analysis of discordant data showed there were fewer non-diagnostic cases in the thin layer smears (377 vs 541, p<0.001) whereas in conventional smears there were more cases positive for carcinoma (27 vs 4, p<0.001). The cytohistologic correlation was available for 194 cases and showed that conventional smears had a greater capacity for revealing carcinomas (44 vs 31). Finally, diagnoses based on conventional smears were more sensitive than thin layer smears (93.6% vs 65.9%) whereas specificity was constant. From our experience, the conventional smear offers a greater possibility of diagnosis when suspecting malignancy or diagnosing malignancy cases, whereas thin layer smears significantly reduce the number of non-diagnostic cases. For this reason, we suggest combining the two techniques in routine cytologic diagnosis.


3-Cyclo-propyl-1-(4-methyl-phenyl-sulfon-yl)piperidine-3,5-diol.
In the title compound, C(15)H(21)NO(4)S, both hy-droxy groups on the piperidine ring are located in axial positions, whereas the tosyl group and the cyclo-propane ring are in equatorial positions. An intra-molecular O-H⋯O hydrogen bond occurs. In the crystal, mol-ecules form inversion dimers via pairs of O-H⋯O hydrogen bonds, generating cyclic R(4) (4)(8) motifs, as noted previously in related diols.


Genomic control of inflammation in experimental atopic dermatitis.
Atopic Dermatitis (AD) or eczema, a recurrent allergic inflammation of the skin, afflicts 10-20% of children and 5% adults of all racial and ethnic groups globally. We report a new topical treatment of AD by a Nuclear Transport Checkpoint Inhibitor (NTCI), which targets two nuclear transport shuttles, importin α5 and importin β1. In the preclinical model of AD, induced by the active vitamin D3 analog MC903 (calcipotriol), NTCI suppressed the expression of keratinocyte-derived cytokine, Thymic Stromal Lymphopoietin (TSLP), the key gene in AD development. Moreover, the genes encoding mediators of TH2 response, IL-4 and its receptor IL-4Rα were also silenced together with the genes encoding cytokines IL-1β, IL-6, IL-13, IL-23α, IL-33, IFN-γ, GM-CSF, VEGF A, the chemokines RANTES and IL-8, and intracellular signal transducers COX-2 and iNOS. Consequently, NTCI suppressed skin infiltration by inflammatory cells (eosinophils, macrophages, and CD4 + T lymphocytes), and reduced MC903-evoked proliferation of Ki-67-positive cells. Thus, we highlight the mechanism of action and the potential utility of topical NTCI for treatment of AD undergoing Phase 1/2 clinical trial (AMTX-100 CF, NCT04313400).


Metabolites of synthetic cannabinoids in hair--proof of consumption or false friends for interpretation?
The detection of drug metabolites in hair is widely accepted as a proof for systemic uptake of the drug, unless the metabolites can be formed as artefacts. However, regarding synthetic cannabinoids, not much is known about mechanisms of incorporation into hair. For a correct interpretation concerning hair findings of these compounds and their metabolites, it is necessary to identify the different routes of incorporation and to assess their contribution to analytical findings. This study presents the results of the LC-ESI-MS/MS analysis of an authentic hair sample taken from a patient with a known history of heavy consumption of synthetic cannabinoids. In the authentic hair sample, 5F-PB-22 and AB-CHMINACA as well as their main metabolites 5F-PB-22 3-carboxyindole, PB-22 5-OH-pentyl, and AB-CHMINACA valine were detected in all segments, comprising segments grown in a time period where the substances had not been distributed on the 'legal high' market. To enable interpretation of the results regarding the distribution of the detected analytes along the hair shaft, the stability of 5F-PB-22 and AB-CHMINACA in hair matrix and under thermal stress was assessed. The stability tests revealed that the three 'metabolites' are also formed in externally contaminated hair after storage of the samples under different conditions. In addition, 5F-PB-22 3-carboxyindole and AB-CHMINACA valine were identified as degradation products in smoke condensate. Therefore, interpretation of 'metabolite' findings of compounds comprising chemically labile amide/ester bonds or 5-fluoro-pentyl side chains should be carried out with utmost care, taking into account the different mechanisms of formation and incorporation into hair.