Differing microvasculature in the two major types of gastric carcinoma: a conventional, ultrastructural and ultrastructural immunolocalization study of von Willebrand factor.
The microvasculature of the stroma of human gastric carcinoma was studied by immuno-electron microscopy for factor VIII/von Willebrand factor (vWF) and conventional electron microscopy. In differentiated type (intestinal) gastric carcinoma (9 cases), capillaries were distributed more densely around carcinoma cell nests. vWF was localized in endothelial cells and neighbouring stroma. Ultrastructurally, capillary endothelial cells showed considerable hypertrophic changes with well-developed rough endoplasmic reticulum (rER). vWF was localized in well-developed rER, granules, Weibel-Palade bodies (WPB), in the vascular lumen as clusters, and diffusely deposited in the subendothelium. This indicates that endothelial cells in this group are transformed into a state of active protein production. In undifferentiated type (diffuse) gastric carcinoma (12 cases), capillaries were uniformly distributed and endothelial hypertrophic changes were less remarkable. vWF was localized in WPB, scanty rER and subendothelial matrix. Solid capillary buds were observed in both types; they were composed of a solid strand of endothelial cells without a visible lumen. Our results reveal that the microvasculature in tumour stroma differs significantly according to its histological type.


Jejuia marina nov., isolated from gravel adjacent to Geommeolle beach on Udo Island, South Korea.
A bacterial strain, JH03(T), was isolated from gravel adjacent to Geommeolle beach on Udo Island, South Korea. The cells were Gram-stain-negative, aerobic, non-motile and rod shaped. The ranges of temperature, pH and NaCl concentration for growth of the bacterium were 10-45 °C, pH 6.0-9.5 and 0.5-5.0 % (w/v), respectively. The major fatty acids of the bacterium were iso-C(15:0) (15.4 %), iso-C(15:1) G (14.1 %), iso-C(16:0) 3-OH (14.1 %), iso-C(17:0) 3-OH (11.5 %) and anteiso-C(15:0) (11.3 %). The major isoprenoid quinone was MK-6. The polar lipids included phosphatidylethanolamine, two unidentified amino lipids and three unidentified lipids. The DNA G+C content was 34.2 mol%. The phylogenetic analysis of the 16S rRNA gene sequences showed that strain JH03(T) was most closely related to Jejuia pallidilutea EM39(T) (96.5 % sequence similarity). Based on the polyphasic analysis, strain JH03(T) is a novel species of the genus Jejuia, for which the name Jejuia marina sp. nov. is proposed. The type strain is JH03(T) (= KCTC 42342(T) = JCM 30601(T)).


Erratum to: Modelling foetal exposure to maternal smoking using hepatoblasts from pluripotent stem cells.
During manuscript proofing, the following sentence was not deleted in the section "Results" at the end of the paragraph: "Both male and female hepatocytes responded in a similar fashion to cotinine, whereas male hepatocyte function was more sensitive to chrysene, fluorene and naphthalene than female hepatocytes".


Status of resistance to Bt maize in Spodoptera frugiperda: lessons from Puerto Rico.
In 2006, reports of potential Spodoptera frugiperda resistance to TC1507 maize in Puerto Rico were received. Subsequent investigation confirmed that pest populations collected from several sites in Puerto Rico were largely unaffected by the Cry1F protein in bioassays, with resistance ratios likely in excess of 1000. Since then, we have continued monitoring populations in Puerto Rico and in southern areas of the mainland US. The majority of the collections from Puerto Rico continue to show high levels of Cry1F resistance whereas populations collected from the southern US mainland continue to show full susceptibility to Cry1F and TC1507 maize. It does not appear that resistant populations have spread to any measurable extent from Puerto Rico to mainland US, nor that local selection pressure from Cry1F-expressing maize or cotton production in the southern US has caused a measurable change in population susceptibility. Lessons learned from Puerto Rico are being applied in other parts of the Americas where TC1507 maize is grown and additional steps being taken to protect the long-term durability of Cry1F in maize in areas where similar selection pressure may be expected. Tactics include using locally-adapted germplasm that contain native Spodoptera resistance, a robust education program to teach end-users about the potential for resistance to develop appropriate crop stewardship, resistance monitoring, and the use of insecticides under high S. frugiperda pressure. Perhaps most importantly, pyramided trait products that produce two or more different Bt proteins are being introduced to further delay resistance development to Cry1F.


The antiinflammatory effects of methotrexate are mediated by adenosine.
In summary, intermittent, low dose methotrexate treatment is: 1.) antiinflammatory in the murine air pouch model of inflammation; 2.) selectively increases intracellular AICAR concentration; 3.) increases adenosine concentration in an inflammatory exudate; and, 4.) inhibits leukocyte accumulation at an inflamed site by a mechanism that is specifically reversed by adenosine deaminase and the adenosine A2 receptor antagonist DMPX but not the A1 antagonist DPCPX. In conclusion, we have demonstrated a novel mechanism for the antiinflammatory action of methotrexate; methotrexate is a nonsteroidal antiinflammatory agent that acts by promoting the release of adenosine which engages A2 receptors on inflammatory cells.


Satellite cells in developing spinal ganglia. An immunohistochemical study.
The present immunohistochemical study investigates the presence and distribution of S-100-containing glial cells in the early stages of development in human spinal ganglia. From the earliest ages investigated immunoreactive cells could be detected in a continuous layer at the periphery as well as inside ganglionic rudiments in close relationship with neural elements, both at the light and ultrastructural levels. The possibility that these glial cells, exhibiting such a distinctive distribution, play a modulatory role on microenvironmental influences during maturation could be taken into account. Neither glial fibrillary acidic protein nor myelin basic protein could be detected at the ages investigated.


Surgeon fatigue does not affect surgical outcomes: a systematic review and meta-analysis.
To systematically review the effects of surgeon fatigue on postoperative mortality and postoperative complications after elective and non-elective surgeries. A database search was conducted for original articles published in PubMed between 2000 and 2020 with the keywords: "surgeon," "sleep deprivation," "sleep deprived," "fatigued," "mortality," "morbidity," and "outcomes." We selected articles that disclosed actual numbers of patients who underwent surgery by fatigued or rested surgeons, rates of postoperative mortality, or total postoperative complications. Of the 1427 articles identified, 16 met the selection criteria and were included. Eight of the 16 also included total postoperative complications. Analysis revealed no significant differences in the rates of postoperative mortality after elective and non-elective surgeries or total postoperative complications of elective surgeries or non-elective surgeries performed by fatigued vs. rested surgeons. The relative risks were 1.03 [95% confidence interval (CI), 0.86-1.24], 1.08 (95% CI, 0.85-1.38), 0.99 (95% CI, 0.95-1.04), and 0.93 (95% CI, 0.67-1.28), respectively. Surgeon fatigue does not affect the rates of postoperative mortality or total postoperative complications after elective surgeries and may have little to no effect on the rates of postoperative mortality or total postoperative complications after non-elective surgeries.


A randomized, double-blind, placebo-controlled trial of misoprostol for oral mucositis secondary to high-dose chemotherapy.
Misoprostol, a synthetic analog of prostaglandin E1, has anti-inflammatory and mucosa-protecting properties. The objective of this study was to evaluate the efficacy of misoprostol oral rinse in reducing the severity of oral mucosal injury caused by high-dose chemotherapy. The study used a randomized, double-blind, placebo-controlled, parallel-group design. Oncology patients receiving myeloablative high-dose chemotherapy, in preparation for a hematopoietic stem cell transplant, were randomized to misoprostol or placebo rinse. The primary outcome measure was the severity of oral mucositis, measured using the modified Oral Mucositis Index. Additional outcome measures included the severity of mouth pain (measured using a Visual Analog Scale and the Pain Affect Faces Scale), duration of hospital stay, and days on total parenteral nutrition. This study was originally planned to accrue 160 subjects but was terminated early due to revised sponsor research priorities. The intent-to-treat population consisted of 22 subjects randomized to misoprostol rinse and 26 subjects randomized to placebo rinse. There was no significant difference between the two groups in mucositis or pain severity. In both groups, duration of hospital stay was approximately 19 days, and number of days on total parenteral nutrition was 17-18 days. There were no serious adverse events attributable to misoprostol rinse. Although this study did not find a beneficial effect of a misoprostol rinse in mucositis secondary to high-dose chemotherapy, the small sample size limits the strength of this conclusion. Given the proposed importance of the prostaglandin pathway in the pathogenesis of oral mucositis, additional studies are warranted.


The EC4 register of European clinical chemists and EC4 activities.
The freedom of movement of people and goods within the European Union (EU) has a large impact for the member states. Particularly within health care it is important to recognize, or if necessary obtain, an adequate level of the quality of profession and practice, so that citizens know that health care is offered in their country at a level comparable to other countries. The importance of recognition also applies to laboratory medicine. European Communities Confederation of Clinical Chemistry (EC4) is the organization of societies for clinical chemistry and laboratory medicine in the EU. In Europe, health care develops in the direction where patients are treated in a health care chain environment. In this chain, patients move quickly from primary health institutes to secondary and tertiary institutes, and vice versa. This situation involves many health care workers including several laboratories. Diagnosis and therapy are now 'core business' of health care. Medical laboratories play an essential role in this. The broad spectrum of medical laboratory investigations make consultancy of medical laboratory specialists ever more important. The quality of both professionals and laboratories, as well as continuity of laboratory data within and between laboratories, are of utmost importance.EC4 is active in giving support to attain such quality. In most countries, this is the case at present. EC4 plays a central role in the Coordination of Automatic Recognition of Equivalence of Standards (CARE), if such a level exists or is achieved. Such CARE is focussed at three levels, the profession, quality of laboratories and calibration of laboratory data. The EC4 Register of European Clinical Chemists is open for colleagues educated in (bio)chemistry, pharmacy, biology as well as medicine, and trained according to the EC4 Syllabus. Equivalence of standards has been granted to national training schemes of 13 European Union countries. Since its opening in 1998, the number of applicants is growing steadily and quickly, reaching 1225 in May 2001.EC4 has published essential criteria for quality systems of medical laboratories, which formed the basis for a ISO draft international standard regarding quality and competence of medical laboratories.EC4 stimulates projects like the Calibration 2000 project in the Netherlands which focus on continuity of laboratory data, within-as well as between-laboratories.


Dilatory capacity of the coronary circulation and its correlation to the arterial vasculature in the canine left ventricle.
The functional capacity of flow limiting myocardial conductance vessels was evaluated in canine hearts. In an isolated heart preparation transmural coronary flow distribution during maximal vasodilation was measured in the unloaded diastolic arrested left ventricle with tracer microspheres. The ratio of subendocardial versus subepicardial (ENDO/EPI) flow in the left ventricular free wall was 1.6. Measurements in 8 different wall layers showed a successive increase in maximal coronary flow from the subepicardium towards the deeper layers. A decreased subendocardial vascular resistance due to a better vascularization is forwarded as a mechanism to compensate for the extravascular compression during cardiac contraction. This statement contradicts the commonly accepted hypothesis that a diminished vascular tone with a reduction of the dilatory reserve in the subendocardium accounts for a homogeneous flow distribution in the normal beating heart. An augmentation of subendocardial supplying vessel capacity could be established from the angiographic determination of the coronary arterial volume of intramural small arteries and arterioles. From a strict parallelity in maximal coronary flow and coronary arterial volume within the wall, it becomes probable that these vascular structures are the flow-limiting factors which determine regional coronary flow reserve in the absence of extravascular compressive forces.


Influence of chronic low back pain and fear of movement on the activation of the transversely oriented abdominal muscles during forward bending.
Chronic low back pain (CLBP) and fear of movement (kinesiophobia) are associated with an overactivation of paravertebral muscles during forward bending. This impairs spine motor control and contributes to pain perpetuation. However, the abdominal muscles activation is engaged too in spine stabilization but its modulation with kinesiophobia remains unknown. Our study tested whether CLBP and kinesiophobia affected the activation pattern of abdominal muscles during trunk flexion/extension. Surface electromyographical recordings of the internal oblique/transversus abdominis (IO/TrA) and external oblique (EO) muscles were analyzed in 12 people with CLBP and 13 pain-free subjects during low-velocity forward bending back and forth from erected posture. Tampa Scale of Kinesiophobia was also administrated. IO/TrA activation, but not EO, was modulated across the phases of movement in both groups, i.e. maximal at onset of flexion and end of extension, and minimal at full flexion. In CLBP group only, IO/TrA activation was increased near to full trunk flexion and in correlation with kinesiophobia. The phase-dependence of IO/TrA activation during trunk flexion/extension in standing may have a role in spine motor control. The influence of kinesiophobia in CLBP should be further investigated as an important target in CLBP management.


Congenital central alveolar hypoventilation (Ondine's curse): a case report and review of the literature.
Congenital central alveolar hypoventilation (C-CAH), so called Ondine's curse, is known to be quite a rare neuropathology that has been reported in only 23 cases to date. C-CAH was diagnosed in a 2-year-5-month-old infant. In the treatment of C-CAH, we implanted a right unilateral diaphragm pacemaker in the infant and his respiratory status was remarkably improved after diaphragm pacing. Twenty-three reported cases of this disorder are reviewed in the literature.


Letter to the editor on article by Dinh et al. Is it ethical to incentivize mammography screening in Medicaid populations? - A policy review and conceptual analysis. By Stamatia Destounis, MD and Sarah Friedewald MD.
Letter to the Editor on article by Dinh et al- response to the authors comments on " Is it ethical to incentivize mammography screening in Medicaid populations? - A policy review and conceptual analysis".


The microlepidopterous natural enemy Brachymeria subrugosa Blanchard, 1942 (Hymenoptera, Chalcididae): identity, hosts and geographic distribution.
A lectotype is designated for Brachymeria subrugosa Blanchard 1942 (Hymenoptera: Chalcididae). The species is diagnosed, redescribed, and compared to B. subconica Bouček, both of which are illustrated by macrophotography. Taxonomic notes, new parasitoid/host associations and new geographical records are also given for B. subrugosa. Brachymeria annulipes (Costa Lima 1919), a junior secondary homonymy of Chalcis annulipes Walker 1834, is proposed as a junior synonym of B. subrugosa syn. nov.


Thyroid hormones and cognitive functioning in healthy, euthyroid women: a correlational study.
Thyroid hormones (THs) play a critical role in differentiation, growth, and metabolism of animal and human organ systems, including the brain. Although associations between normal levels of THs and cognitive functions in healthy elderly individuals have been reported, the findings are inconsistent, possibly due to differences in study designs. Because thyroid disease occurs more frequently in women, the goal of the present study was to examine the relationship between levels of THs and performance on neuropsychological tests in 122 healthy, euthyroid women whose mean age was 51 years. Higher levels of free T3 were positively associated with longer completion times (slower performance) on Trail Making Test - Part A (p = 0.006) and Part B (p = 0.032) and on the Tower of London test (p = 0.002). Higher levels of thyroglobulin antibodies (TgAb) were positively correlated with more errors on the Trail Making Test Part B (p = 0.000), on the Word Fluency test (p = 0.023), and on the Design Fluency test (p = 0.045). No significant correlations between TH levels and scores on mood, verbal memory, or working memory measures were observed. The findings point to a possible link between THs and cognitive processes that are mediated primarily by frontal cortex, areas associated with executive function tasks, and suggest that elevations in levels of free T3 and TgAB within the normal range may negatively influence executive functions.


1-Naphthyl acetate: A chromogenic substrate for the detection of erythrocyte acetylcholinesterase activity.
Erythrocyte acetylcholinesterase (AChE) is a preferred biomarker for the detection of organophosphorus poisoning. Acetylthiocholine (ATCh) is the most popular substrate for the detection of AChE activity. However, oximolysis is a prominent feature with ATCh. In this context, we have searched alternative substrates for AChE using in silico tools for screening of a better substrate. The in silico approach was performed to understand the fitness and the Total Interaction Energy (TIE) of substrates for AChE. The alternative substrates for AChE were screened in terms of high Goldscore and favorable TIE in comparison to acetylcholine (ACh)-AChE complex and other relevant esterases. Among the screened substrates, 1-Naphthyl acetate (1-NA) exhibited the most favorable interaction with AChE in terms of highest TIE and corresponding high Goldscore. The Molecular Dynamic (MD) simulation of the 1-NA-AChE complex showed a stable complex formation over a period of 5 ns. The results obtained in the in silico studies were validated in vitro using pure erythrocyte AChE and hemolysate. We observed 1-NA to be a better alternative substrate for AChE than ATCh in terms of lower Km value. Its specificity appeared at least similar to ATCh. Therefore, we propose that 1-NA can be an attractive chromogenic substrate for the measurement of AChE activity, and it possess the potential to detect organophosphorus pesticide (OP) poisoning.


Cross-country differences in age trends in alcohol consumption among older adults: a cross-sectional study of individuals aged 50 years and older in 22 countries.
Age-related changes in physiological, metabolic and medication profiles make alcohol consumption likely to be more harmful among older than younger adults. This study aimed to estimate cross-national variation in the quantity and patterns of drinking throughout older age, and to investigate country-level variables explaining cross-national variation in consumption for individuals aged 50 years and older. Cross-sectional observational study using previously harmonized survey data. Twenty-two countries surveyed in 2010 or the closest available year. A total of 106 180 adults aged 50 years and over. Cross-national variation in age trends were estimated for two outcomes: weekly number of standard drink units (SDUs) and patterns of alcohol consumption (never, ever, occasional, moderate and heavy drinking). Human Development Index and average prices of vodka were used as country-level variables moderating age-related declines in drinking. Alcohol consumption was negatively associated with age (risk ratio = 0.98; 95% confidence interval = 0.97, 0.99; P-value < 0.001), but there was substantial cross-country variation in the age-related differences in alcohol consumption [likelihood ratio (LR) test P-value < 0.001], even after adjusting for the composition of populations. Countries' development level and alcohol prices explained 31% of cross-country variability in SDUs (LR test P-value < 0.001) but did not explain cross-country variability in the prevalence of heavy drinkers. Use and harmful use of alcohol among older adults appears to vary widely across age and countries. This variation can be partly explained both by the country-specific composition of populations and country-level contextual factors such as development level and alcohol prices.


Differences in heme and hemopexin content in lipoproteins from patients with sickle cell disease.
High blood cholesterol is associated with atherogenesis and endothelial dysfunction. The latter is present in hemolytic diseases, such as sickle cell anemia, whose carriers have hypocholesterolemia and low incidence of coronary artery disease. We aimed to characterize cholesterol fractions in patients with sickle cell disease and explore the relationship among lipoproteins, varying degrees of hemolysis, and its biomarkers. We recruited 37 healthy individuals, 39 with hemoglobin SC disease, and 40 with sickle cell anemia and quantified cholesterol fractions, heme resulting from hemoglobin breakdown, and its main scavenger protein hemopexin. Hypocholesterolemia was most significant in patients with sickle cell anemia, and cholesterol levels correlated positively with hemopexin. Nevertheless, patients still had higher relative low-density lipoprotein (LDL) oxidation than healthy subjects. Analysis of lipoproteins isolated by density ultracentrifugation showed that the LDL fraction contained higher concentrations of heme than the high-density lipoprotein (HDL) fraction, whereas HDL contained more hemopexin than LDL, albeit greatly reduced in patients. Our findings show that the abnormally low lipoprotein levels in sickle cell anemia correlate with hemolysis markers, particularly with hemopexin concentrations, along with significant reduction of this heme scavenger in HDL fractions. This may suggest an important role for HDL in the defense against heme-induced endothelial dysfunction in hemolytic diseases.


Utility of intraoperative parathyroid hormone monitoring in patients with multiple endocrine neoplasia type 1-associated primary hyperparathyroidism undergoing initial parathyroidectomy.
Intraoperative parathyroid hormone monitoring (IOPTH) is a widely used adjunct for primary hyperparathyroidism (pHPT). However, the benefit of IOPTH in familial pHPT, such as in multiple endocrine neoplasia type I (MEN1), remains unclear. We performed a retrospective analysis of 52 patients with MEN1-associated pHPT undergoing initial parathyroidectomy with IOPTH monitoring at our institution. Parathyroid hormone (PTH) levels were measured before skin incision and 10 min after resection of the last parathyroid gland. Variables analyzed included percent drop of PTH from baseline and the final PTH level compared to the normal reference range (RR). A total of 52 patients underwent initial subtotal parathyroidectomy with IOPTH. An IOPTH decrease cutoff of ≥75 % from baseline had the highest biochemical cure rate (87 %). In the remaining 13 % who met this cutoff, all had persistent pHPT, with ≥90 % drop of PTH from baseline. The remaining patients, who did not meet the ≥75 % cutoff, were cured. Follow-up was available for three of four patients with final IOPTH levels above the RR: one had persistent pHPT, two had hypoparathyroidism (50 %). When a postresection PTH level was within the RR, 88 % of patients were cured. While considered cured from pHPT, 7 % of patients in this group developed permanent hypoparathyroidism. When the final PTH level dropped below the RR, 28 % developed permanent hypoparathyroidism. A cutoff in IOPTH decrease of ≥75 % from baseline has the highest biochemically cure rate in patients with pHPT associated with MEN1. However, a 75 % cutoff in IOPTH decrease does not exclude persistent pHPT. The absolute IOPTH value does not accurately predict postoperative hypoparathyroidism.


Light-source-dependent role of nitrate and humic acid in tetracycline photolysis: kinetics and mechanism.
To elucidate the environmental fate of tetracycline (TC), we reported the light-source-dependent dual effects of humic acid (HA) and NO3(-) on TC photolysis. TC photolysis rate was highly pH- and concentration-dependent, and was especially enhanced at higher pH and lower initial TC concentrations. Under UV-254 and UV-365 irradiation, HA inhibited TC photolysis through competitive photoabsorption or reactive oxygen species (ROS) quenching with TC; under solar and xenon lamp irradiation, TC photolysis was enhanced at low HA concentration due to its photosensitization, whereas was suppressed at high HA concentration due to competitive photoabsorption or ROS quenching with TC. Similarly, the effect of NO3(-) on TC photolysis varied with light irradiation conditions. Even under the same light irradiation conditions, the effects of HA or NO3(-) on TC photolysis varied with their concentrations. The electron spin resonance spectrometer and ROS scavenger experiments demonstrated that TC photolysis was involved in O2(-)-mediated self-sensitized photolysis. The photolysis pathways were involved in hydroxylation and loss of some groups. More toxic intermediates than TC were generated under different light irradiation conditions. These results can provide insight into the potential fate and transformation of TC in surficial waters.


Effect of plant secondary compounds on in vitro methane, ammonia production and ruminal protozoa population.
The objective of this study was to evaluate the potential of secondary plant metabolites from 38 sources to serve as antimethanogenic additives in ruminant diets. The effect of leaf tannins from these different plant sources on rumen fermentation, protozoal populations and methanogenesis was also studied. Samples (200 mg dry matter, DM) were incubated without and with polyethylene glycol (PEG)-6000 (400 mg DM) as a tannin binder during 24-h incubation in the in vitro Hohenheim gas system. In the leaf samples, total phenol (g kg(-1) DM) was maximum in Pimenta officinalis (312) followed by Oenothera lamarckiana (185) and Lawsonia inermis (105). Of the 38 samples, condensed tannins exceeded 4.0 g kg(-1) in only Alpinia galanga (7.50), Cinnamomum verum (4.58), Pelargonium graveolens (18.7) and Pimenta officinalis (23.2) and were not detected in seven samples. When the bioactivity of the leaf samples was assessed using the tannin bioassay, the percentage increase in the amount of gas produced during incubation of samples with the tannin-binding agent PEG-6000 over the amount produced during incubation without the tannin binder ranged from nil (zero) to 367%, with the highest being recorded with A. galanga leaves. The ratio of methane reduction per ml of total gas reduction was maximum with Rauvolfia serpentina (131.8) leaves, followed by Indigofera tinctoria (16.8) and Withania somnifera (10.2) leaves. Total and differential protozoal counts increased with added PEG in twenty-two samples, maximum being in Pimenta officinalis. Increased accumulation of total volatile fatty acids during incubation with added PEG-6000 was recorded, and the values ranged from zero to 61%. However, the increase was significant in only 11 of the 38 tannin sources tested indicating noninterference of tannin on in vitro fermentation of carbohydrates by the majority of samples tested. Conversely, in 26 of 38 plant sources, the leaf tannins reduced N-digestibility as evidenced by increased accumulation of NH3 -N with added PEG. Our study unequivocally demonstrated that plants containing secondary metabolites such as Rauvolfia serpentine, Indigofera tinctoria and Withania somnifera have great potential to suppress methanogenesis with minimal adverse effect of feedstuff fermentation. It was established that methanogenesis was not essentially related to the density of protozoa population in vitro. The tannins contained in these plants could be of interest in the development of new additives in ruminant nutrition.


The relationship between the umbilicus and the aortic bifurcation in Turkish women: implications for laparoscopic entry.
We aimed to determine the location and vertical distance of the umbilicus relative to the aortic bifurcation using computed tomography (CT), and assess their relationship with BMI among Turkish women and their implications for laparoscopic entry. This cross-sectional study included a total of 209 women undergoing abdominopelvic CT; the vertical distance between the aortic bifurcation and the umbilicus was evaluated on coronal sections. The distance between the skin and the parietal peritoneum was measured from the umbilical pit to the peritoneum, and the distance between the skin and the aorta was measured from the umbilical pit to the surface of the aortic bifurcation. The measurements were performed along the sagittal plane. The age, height, and weight of the patients were recorded. For comparison, women were divided into three groups according to BMI. The aortic bifurcation was located above (cephalic to) the umbilicus in 30 patients in the non-obese group (48.4%), 54 patients in the overweight group (55.7%), and 34 patients (68%) in the obese group. The mean distances between the umbilicus and the parietal peritoneum were 15.1 ± 6.4, 19 ± 5.5, 27.2 ± 10.8 mm, respectively, in the non-obese group, overweight group, and obese group. The mean distances between the umbilicus and the aorta were 85.8 ± 26.3, 110 ± 2.9, 132.1 ± 26.7 mm, respectively, in the non-obese group, overweight group, and obese group. The location of the umbilicus relative to the aortic bifurcation can vary according to age, BMI and ethnicity or nationality of patients; therefore, a surgeon should not stick to a particular angle of insertion during laparoscopic entry. It is better for surgeons to know their unique patient population.


Characterization of a protease produced by a Trichoderma harzianum isolate which controls cocoa plant witches' broom disease.
Several Trichoderma strains have been reported to be effective in controlling plant diseases, and the action of fungal hydrolytic enzymes has been considered as the main mechanism involved in the antagonistic process. However, although Trichoderma strains were found to impair development of Crinipellis perniciosa, the causal agent of cocoa plant witches' broom disease, no fungal strain is available for effective control of this disease. We have then undertaken a program of construction of hydrolytic enzyme-overproducing Trichoderma strains aiming improvement of the fungal antagonistic capacity. The protease of an indian Trichoderma isolate showing antagonistic activity against C. perniciosa was purified to homogeneity and characterized for its kinetic properties and action on the phytopathogen cell wall. A protease produced by the Trichoderma harzianum isolate 1051 was purified to homogeneity by precipitation with ammonium sulfate followed by hydrophobic chromatography. The molecular mass of this protease as determined by SDS-polyacrylamide gel electrophoresis was about 18.8 kDa. Its N-terminal amino acid sequence shares no homology with any other protease. The purified enzyme substantially affected the cell wall of the phytopathogen C. perniciosa. Western-blotting analysis showed that the enzyme was present in the culture supernatant 24 h after the Trichoderma started to grow in casein-containing liquid medium. The capacity of the Trichoderma harzianum protease to hydrolyze the cell wall of C. perniciosa indicates that this enzyme may be actually involved in the antagonistic process between the two fungi. This fact strongly suggest that hydrolytic enzyme over-producing transgenic fungi may show superior biocontrol capacity.


Transcriptional changes during neuronal death and replacement in the olfactory epithelium.
The olfactory epithelium has the unusual ability to replace its neurons. We forced replacement of mouse olfactory sensory neurons by bulbectomy. Microarray, bioinformatics, and in situ hybridization techniques detected a rapid shift in favor of pro-apoptotic proteins, a progressive immune response by macrophages and dendritic cells, and identified or predicted 439 mRNAs enriched in olfactory sensory neurons, including gene silencing factors and sperm flagellar proteins. Transcripts encoding cell cycle regulators, axonogenesis proteins, and transcription factors and signaling proteins that promote proliferation and differentiation were increased at 5--7 days after bulbectomy and were expressed by basal progenitor cells or immature neurons. The transcription factors included Nhlh 1, Hes 6, Lmyc 1, c-Myc, Mxd 4, Id 1, Nmyc 1, Cited 2, c-Myb, Mybl 1, Tead 2, Dp 1, Gata 2, Lmo 1, and Sox1 1. The data reveal significant similarities with embryonic neurogenesis and make several mechanistic predictions, including the roles of the transcription factors in the olfactory sensory neuron lineage.


Effects of an industrial effluent on plant colonization and on the germination and post-germinative growth of seeds of terrestrial and aquatic plant species.
Major oil sands industrial companies are located in the Athabasca Oil Sands Deposit in northeastern Alberta, Canada. During the process used to extract light crude oil (via hot water digestion and flotation), gypsum is usually added to produce consolidated tails (CT) and CT release water. The vast volumes of process-treated waters (effluent) are held within large dyked tailings ponds. Toward testing viable options for reclamation, various hummock-wetlands systems have been constructed; in addition, natural wetlands (inhabited by obligate wetland plant species) have become established as a result of seeping of the effluents held within the large dyked ponds. Vegetation surveys conducted on and around the industrial site revealed that the constructed wetlands associated with the dyke drainage (effluent treated with phosphorous) and consolidated tails (CT; effluent treated with gypsum) had low biodiversity and were not invaded by many aquatic plants. Although the natural wetland was also not invaded by many aquatic species, it was found to be as diverse as the reference wetlands (i.e. off-site wetlands not exposed to the effluents). Exposure to oil sands effluents had an inhibitory effect on the germination (percent and/or rate) of several plant species (tomato, clover, wheat, rye, pea, reed canary grass, loblolly pine); clover and tomato seed germination were most affected. Two treatments in particular (effluents from the natural on-site wetland and the CT constructed wetland), delayed germination, and also led to reduced fresh weight of seedlings of tomato, wheat, clover and loblolly pine. The osmolarities of the effluents associated with the natural on-site wetland and CT constructed wetland were 712 and 728 mOs/kg, respectively; substituting these effluents with solutions of polyethylene glycol of the same osmotic potentials had a greater inhibitory effect on germination rate. The negative effects of the effluents on seed germination may account for the paucity of aquatic species that invaded the oil sands impacted wetlands. This factor will also be critical in determining the long-term feasibility of hummock-wetland systems.


Greater dapivirine release from the dapivirine vaginal ring is correlated with lower risk of HIV-1 acquisition: a secondary analysis from a randomized, placebo-controlled trial.
A vaginal ring containing 25 mg of the antiretroviral dapivirine has demonstrated efficacy in reducing women's risk of sexually acquiring HIV-1; however, imperfect ring use likely diluted efficacy estimates in clinical trials. The amount of dapivirine remaining in returned rings may reflect the extent of product use, permitting estimation of HIV protection in the context of consistent use. We measured the amount of dapivirine in returned rings from a placebo-controlled trial of the dapivirine vaginal ring conducted between August 2012 and June 2015 among 2629 African women. Phase I/II studies established that greater than 4 mg of dapivirine on average is released from the ring when used consistently over 28 days and ≤0.9 mg released suggested non-use. We assessed the relative risk reduction associated with levels of ring use using residual dapivirine in returned rings as a time-dependent covariate for HIV-1 infection in multivariable Cox models, including multiple exploratory analyses designed to estimate upper limits of efficacy given uncertainty in timing of HIV-1 acquisition. All models were adjusted for baseline covariates associated with HIV risk and adherence. Residual dapivirine levels indicating at least some use (>0.9 mg released over a month) were associated with a 48% relative reduction in HIV-1 acquisition risk (95% confidence interval (CI): 21% to 66%; p = 0.002) compared to the placebo. Exploratory analyses accounting for potential misclassification in timing of HIV-1 acquisition estimated 75% to 91% HIV-1 risk reduction with> 4 mg released when compared to placebo. Results limited to the subgroup of women <25 years of age, who tended to have lower adherence, were generally consistent to those overall. Residual dapivirine levels, an objective measure of adherence, were correlated with HIV-1 protection in a secondary analysis of a randomized trial. Periods of ring use were associated with approximately 50% protection, with exploratory analyses suggesting higher protection with more consistent use. The dapivirine vaginal ring is the first method to fulfil the promise of a fully reversible, long-acting, woman-initiated approach for discreet HIV-1 prevention.


Individual and joint associations of long-term exposure to air pollutants and cardiopulmonary mortality: a 22-year cohort study in Northern China.
Evidence on the associations between long-term exposure to multiple air pollutants and cardiopulmonary mortality is limited, especially for developing regions with higher pollutant levels. We aimed to characterise the individual and joint (multi-pollutant) associations of long-term exposure to air pollutants with cardiopulmonary mortality, and to identify air pollutant that primarily contributes to the mortality risk. We followed 37,442 participants with a mean age of 43.5 years in four cities in northern China (Tianjin, Shenyang, Taiyuan, and Rizhao) from January 1998 to December 2019. Annual particulate matter (PM) with diameters ≤2.5 μm (PM2.5), ≤10 μm (PM10), sulfur dioxide (SO2) and nitrogen dioxide (NO2) were estimated using daily average values from satellite-derived machine learning models and monitoring stations. Time-varying Cox proportional hazards model was used to evaluate the individual association between air pollutants and mortality from non-accidental causes, cardiovascular diseases (CVDs), non-malignant respiratory diseases (RDs) and lung cancer, accounting for demographic and socioeconomic factors. Effect modifications by age, sex, income and education level were also examined. Quantile-based g-Computation integrated with time-to-event data was additionally applied to evaluate the co-effects and the relative weight of contributions for air pollutants. During 785,807 person-years of follow-up, 5812 (15.5%) died from non-accidental causes, among which 2932 (7.8%) were from all CVDs, 479 (1.3%) from non-malignant RDs, and 552 (1.4%) from lung cancer. Long-term exposure to PM10 (mean [baseline]: 136.5 μg/m3), PM2.5 (mean [baseline]: 70.2 μg/m3), SO2 (mean [baseline]: 113.0 μg/m3) and NO2 (mean [baseline]: 39.2 μg/m3) were adversely and consistently associated with all mortality outcomes. A 10 μg/m3 increase in PM2.5 was associated with higher mortality from non-accidental causes (hazard ratio 1.20; 95% confidence interval 1.17-1.23), CVDs (1.23; 1.19-1.28), non-malignant RDs (1.37; 1.25-1.49) and lung cancer (1.14; 1.05-1.23). A monotonically increasing curve with linear or supra-linear shape with no evidence of a threshold was observed for the exposure-response relationship of mortality with individual or joint exposure to air pollutants. PM2.5 consistently contributed most to the elevated mortality risks related to air pollutant mixture, followed by SO2 or PM10. There was a strong and positive association of long-term individual and joint exposure to PM10, PM2.5, SO2, and NO2 with mortalities from non-accidental causes, CVDs, non-malignant RDs and lung cancer in high-exposure settings, with PM2.5 potentially being the main contributor. The shapes of associations were consistent with a linear or supra-linear exposure-response relationship, with no lower threshold observed within the range of concentrations in this study. National Key Research and Development Program of China, the China Scholarship Council, the National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province.


Structural imaging in children with chronic focal epilepsy: diagnostic algorithms and exploration strategies.
Malformations of cortical development, especially focal cortical dysplasia in infants and children, and hippocampal sclerosis in adolescents with epilepsy are frequent lesions, but they are overlooked on standard MRI. In infants, errors in the interpretation of MRI in epilepsy can be attributed to MRI signal changes due to ongoing myelination. Poor technique, perceptual misses, incomplete knowledge and poor judgment are, however, other likely sources of errors when reading MRIs. This review covers MRI search strategies, i.e., how to conduct MRI examinations in epilepsy and what to expect in the structural MRI of an infant or child with focal epilepsy. Exploiting increased sensitivity, false positive results can be avoided in the light of a clinical hypothesis, possibly isolating a localized brain area by seizure semiology, EEG, and sometimes PET prior to MR reading.


From oocyte to baby: a clinical evaluation of the biological efficiency of in vitro fertilization.
To assess the real biological efficiency of assisted reproduction technology (ART) cycles by using a new metric called oocyte to baby rate, where live babies born (LBB) are reported in relation to the number of oocytes retrieved and used. Retrospective analysis of clinical and embryological database. University center. Patient's cycles (n = 572) divided by age (<35, 35 to 37, 38 to 40, 41 to 42, >42 years) and by oocyte donors. None. Total number of oocytes collected, the number of embryos transferable (fresh and frozen) and corresponding oocyte to LBB rates. In patients with remaining frozen embryos, the final LBB was estimated according to our reported rates. A total of 572 oocyte retrievals yielded 7213 oocytes. The total number of transferred and frozen embryos was 2252 (a utilization rate of 31.2%). The LBB from fresh embryo transfers was 262 with an additional 64 LBB expected from frozen embryos. The overall oocyte to LBB rate was 4.6% (326 babies born). When analyzed by groups, the oocyte to baby rate was best in donor oocyte cycles (6.8%), and declined to 1% for patients >40. There was no increase in oocyte to LBB if >15 oocytes were obtained. During ART cycles, only approximately 5% of fresh oocytes produce a baby. The time has come to investigate new methods of oocyte viability assessment and consider changing current ART practice to recruit fewer oocytes.


Cardiac ischemia-reperfusion injury induces ROS-dependent loss of PKA regulatory subunit RIα.
Type I PKA regulatory α-subunit (RIα; encoded by the Prkar1a gene) serves as the predominant inhibitor protein of the catalytic subunit of cAMP-dependent protein kinase (PKAc). However, recent evidence suggests that PKA signaling can be initiated by cAMP-independent events, especially within the context of cellular oxidative stress such as ischemia-reperfusion (I/R) injury. We determined whether RIα is actively involved in the regulation of PKA activity via reactive oxygen species (ROS)-dependent mechanisms during I/R stress in the heart. Induction of ex vivo global I/R injury in mouse hearts selectively downregulated RIα protein expression, whereas RII subunit expression appears to remain unaltered. Cardiac myocyte cell culture models were used to determine that oxidant stimulus (i.e., H2O2) alone is sufficient to induce RIα protein downregulation. Transient increase of RIα expression (via adenoviral overexpression) negatively affects cell survival and function upon oxidative stress as measured by increased induction of apoptosis and decreased mitochondrial respiration. Furthermore, analysis of mitochondrial subcellular fractions in heart tissue showed that PKA-associated proteins are enriched in subsarcolemmal mitochondria (SSM) fractions and that loss of RIα is most pronounced at SSM upon I/R injury. These data were supported via electron microscopy in A-kinase anchoring protein 1 (AKAP1)-knockout mice, where loss of AKAP1 expression leads to aberrant mitochondrial morphology manifested in SSM but not interfibrillar mitochondria. Thus, we conclude that modification of RIα via ROS-dependent mechanisms induced by I/R injury has the potential to sensitize PKA signaling in the cell without the direct use of the canonical cAMP-dependent activation pathway.NEW & NOTEWORTHY We uncovered a previously undescribed phenomenon involving oxidation-induced activation of PKA signaling in the progression of cardiac ischemia-reperfusion injury. Type I PKA regulatory subunit RIα, but not type II PKA regulatory subunits, is dynamically regulated by oxidative stress to trigger the activation of the catalytic subunit of PKA in cardiac myocytes. This effect may play a critical role in the regulation of subsarcolemmal mitochondria function upon the induction of ischemic injury in the heart.


Outlined elements, regular elements and coincidences in illusory-figure patterns.
When elements in a pattern which would otherwise produce an illusory figure are modified by outlining or by increasing their regularity (in accordance with a proposed measure of the latter quality), the illusory effect is much reduced. Both results reflect the principle that 'coincidences' in a display play little or no role in the process of segmentation when other circumstances tend to force critical edges to 'belong' to individual elements of the display.


Angiotensin-converting enzyme (ACE) I/D corrected serum ACE activity and severity assessment of community-acquired pneumonia.
Various studies have described decreased serum angiotensin-converting enzyme (ACE) activity in patients with pneumonia. The aim of the present study was to evaluate the role of ACE in pneumonia by comparing ACE insertion/deletion (I/D) genotype corrected serum ACE activity and to establish whether the severity of the disease correlates with lower ACE activity. This was a prospective hospital-based observational study including 134 patients with pneumonia. Serum ACE activity was determined at admission, on days 2, 3, 5 and 10 of hospital stay, and at recovery. Based on ACE genotype and reference values, corresponding Z-scores were calculated. Disease severity, quantified by the acute physiology score (APS), and clinical outcome were compared between tertile groups of the Z-scores. A significant decrease in serum ACE activity during an episode of pneumonia with return to control range during recovery was observed for all three genotypes (II, ID and DD). The calculated Z-scores showed a negative correlation with APS scores (p=0.050). No significant association between decreased serum ACE activity and clinical outcome was observed. Serum ACE activity is significantly decreased during the acute phase of pneumonia. Despite correction for ACE I/D genotype, decreased ACE activity did not show a prognostic value. Further studies are needed to examine the mechanisms behind and diagnostic value of decreased ACE activity in community-acquired pneumonia.


Polycystic disease of the parotid glands: two familial cases.
Polycystic (dysgenetic) disease of the parotid glands is a rare disorder with only three fully documented reports in the literature containing a total of six cases. This developmental disorder of the distal ductal system appears limited to the parotid glands of female patients and is usually bilateral. We present two further cases with a confirmed familial background to add to the literature. This is the first documented report of familial polycystic disease of the parotid glands. The pathogenesis, mode of inheritance, clinical features, histological appearance and management of this interesting condition are discussed.


Comparison of the Peritoneal Cancer Index and Dutch region count as tools to stage patients with peritoneal metastases of colorectal cancer.
Extent of peritoneal metastases (PM) is among the most powerful prognostic factors for survival after cytoreductive surgery (CRS). This study aimed to compare the Peritoneal Cancer Index (PCI) and the Dutch region count as tools for staging PM of colorectal cancer. The Dutch region count is a simpler classification that distinguishes seven rather than 13 abdominal regions. Presence or absence of PM is recorded. This was a retrospective cohort study in two tertiary referral centres in the Netherlands. Consecutive patients with colorectal PM who were intentionally treated with CRS and subsequent hyperthermic intraperitoneal chemotherapy in 2016 and 2017 were included. The PCI and Dutch region count were both recorded during laparotomy. Correlation between scoring tools was calculated using Spearman's rank correlation coefficient. Diagnostic values were calculated for different cut-off values of the PCI, alongside the Dutch region count. The correlation of both scores was determined for the exploration and validation cohorts separately. In the exploration and validation cohorts, 73 and 85 patients respectively were included. Spearman's correlation coefficients of 0·897 and 0·961 were observed for continuous scores of the Dutch region count and PCI in the exploration and validation group respectively. A cut-off value of 20 for the PCI score and 5 for the Dutch region count showed 91·9 and 94·5 per cent sensitivity, and 81·8 and 91·7 per cent specificity, respectively. The Dutch region count correlated well with the PCI score, and may help to simplify reporting of the extent of peritoneal disease.


Phylogenetic analysis based on single-copy orthologous proteins in highly variable chloroplast genomes of Corydalis.
Corydalis is one of the few lineages that have been reported to have extensive large-scale chloroplast genome (cp-genome) rearrangements. In this study, novel cp-genome rearrangements of Corydalis pinnata, C. mucronate, and C. sheareri are described. C. pinnata is a narrow endemic species only distributed at Qingcheng Mountain in southwest China. Two independent relocations of the same four genes (trnM-CAU-rbcL) were found relocated from the typically posterior part of the large single-copy region to the front of it. A uniform inversion of an 11-14-kb segment (ndhB-trnR-ACG) was found in the inverted repeat region; and extensive losses of accD, clpP, and trnV-UAC genes were detected in all cp-genomes of all three species of Corydalis. In addition, a phylogenetic tree was reconstructed based on 31 single-copy orthologous proteins in 27 cp-genomes. This study provides insights into the evolution of cp-genomes throughout the genus Corydalis and also provides a reference for further studies on the taxonomy, identification, phylogeny, and genetic transformation of other lineages with extensive rearrangements in cp-genomes.


The effect of post-mastectomy radiation in women with one to three positive nodes enrolled on the control arm of BCIRG-005 at ten year follow-up.
We evaluated the effect of post-mastectomy radiation (PMRT) in 1-3 positive lymph nodes (LN) in patients who received uniform modern systemic therapy. Cohort study using individual data collected for 1,649 node-positive women who received doxorubicin/cyclophosphamide with sequential docetaxel in 2000-2003 on the control arm of BCIRG-005. All women underwent mastectomy or lumpectomy and axillary LN dissection. PMRT was given at investigator's discretion. A total of 523 women with 1-3 positive LN underwent mastectomy and 39% (206/523) received PMRT. With a median follow-up of 10years, PMRT improved loco-regional control (LRC) from 91% to 98% (p=0.001) but had no effect on overall survival (OS) (84% vs. 86%, p=0.9). On multivariate analysis, PMRT improved local control (LC) (hazard ratio, 0.14; 95% CI, 0.03-0.62; p=0.01) and LRC (hazard ratio, 0.15; 95% CI, 0.04-0.50; p=0.002). PMRT did not significantly impact OS on multivariate analysis (hazard ratio, 0.91; 95% CI, 0.55-1.51; p=0.7). Results remained consistent with the use of propensity score analysis. In this cohort of patients with N1 disease treated with modern systemic therapy, PMRT improves LRC but has no effect on OS. The rates of OS were excellent, irrespective of adjuvant radiation.


Apurinic endonuclease activity from wild-type and repair-deficient mei-9 Drosophila ovaries.
An endonuclease which acts on apurinic (AP) sites in DNA was partially purified from Drosophila ovaries. The enzyme present in the female germ line has a molecular weight of 63,000 daltons, is Mg++ dependent, and produces a site upon cleaving depurinated DNA that supports DNA repair synthesis. Although the same characteristics are shared by the enzyme present in the excision-deficient mutant mei-9, specific activity for the AP endonuclease is reduced 98% when compared with that found for its wild-type counterpart. Moreover, cross-reactivity toward an antibody that recognizes the wild-type AP endonuclease protein is reduced roughly 90% for partially purified preparations from mei-9. Mixing experiments between extracts of mei-9 and wild type suggest that the mei-9 structural gene somehow alters or influences the levels of the AP endonuclease protein, but in view of the complex phenotype of this mutant the endonuclease is probably not the product of the gene itself.


A 13-week oral toxicity study of senna in the rat with an 8-week recovery period.
Senna was administered by gavage to Sprague Dawley rats once daily at dose levels of 0, 100, 300, 750 or 1500 mg/kg for up to 13 consecutive weeks followed by an 8-week recovery period for selected animals. Dose- and treatment-related clinical signs included abnormal feces, which were seen to varying degrees from animals at 300 mg/kg per day and more. Animals receiving 750 or 1500 mg/kg per day had significantly reduced body weight gain (males only) and, related to the laxative properties of senna, increased water consumption and notable changes in electrolytes in both serum and urine. At both the terminal and recovery phase necropsy, an increase in absolute and relative kidney weights was seen for male and female animals receiving 750 and/or 1500 mg/kg per day. A dark discoloration of the kidneys was observed at necropsy along with histopathological changes in the kidneys (slight to moderate tubular basophilia and pigment deposits) at 300 mg/kg and above. However, there were no indications in laboratory parameters of any renal dysfunction. In addition, for all treated groups, minimal to slight hyperplasia was recorded in the forestomach and large intestine. Following 8 weeks of recovery, with the exception of the brown pigment in the kidneys, there were no histopathological abnormalities. Thus, the biochemical and morphological changes seen following 13 weeks of treatment of senna significantly reversed following 8 weeks of recovery.


Evolution of blood-brain barrier damage associated with changes in brain metabolites following acute ischemia.
Stroke is a serious medical condition that requires emergency care. In the case of ischemic stroke, ischemia may lead to damage to the blood-brain barrier (BBB); the damage in turn may exacerbate the condition. Therefore, noninvasive detection of BBB damage represents a challenge for experimental and clinical researchers. In this study, we assessed the onset of BBB disruption by means of T1-weighted images with administration of the contrast enhancement agent gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and related BBB breakdown to brain metabolite changes in proton magnetic resonance spectrum (H-MRS) in the infarcted site following middle cerebral artery occlusion (MCAO) in rats. It was shown that MCAO for 30 min and 1.5 h caused no Gd-DTPA signal change in the T1-weighted images, whereas MCAO for 1 h significantly altered some of H-MRS brain metabolites, suggesting that brain metabolite changes occurred earlier than BBB damage after ischemic stroke. MCAO for 2 h caused BBB breakdown, which was related to changes in the levels of some brain metabolites detected by H-MRS. Between the second and the third hour after MCAO, brain metabolite changes continued as the result of BBB breakdown and the concurrent overperfusion to the infarcted site, which may ameliorate the metabolite changes, thus compensating for the functional failures of the brain after stroke.


Targeting motifs in frustule-associated proteins from the centric diatom Thalassiosira pseudonana.
The frustule of diatoms has an exceptional structure composed of inorganic and organic molecules. In the organic fraction, protein families were identified whose members are expected to have a complex cellular targeting to their final location within the frustule. Here we investigated for frustule-targeting signals two representatives of the cingulin family, the proteins CinY2 and CinW2; beside an already known, classical signal peptide, we have identified further regions involved in cellular targeting. By using these regions as a search criteria we were able to identify two new frustule proteins. In addition, we showed that the temporal regulation of the gene expression determines the final location of one cingulin. Our results therefore point to a sophisticated cellular and extracellular targeting of frustule components to build the fascinating frustule structure of a diatom.


Quantifying bias and precision of kinetic parameter estimation on the PennPET Explorer, a long axial field-of-view scanner.
Long axial field-of-view (AFOV) PET scanners allow for full-body dynamic imaging in a single bed-position at very high sensitivity. However, the benefits for kinetic parameter estimation have yet to be studied. This work uses (1) a dynamic GATE simulation of [18F]-fluorothymidine (FLT) in a modified NEMA IQ phantom and (2) a lesion embedding study of spheres in a dynamic [18F]-fluorodeoxyglucose (FDG) human subject imaged on the PennPET Explorer. Both studies were designed using published kinetic data of lung and liver cancers and modeled using two tissue compartments. Data were reconstructed at various emulated doses. Sphere time-activity curves (TACs) were measured on resulting dynamic images, and TACs were fit using a two-tissue-compartment model (k4 ≠ 0) for the FLT study and both a two-tissue-compartment model (k4 = 0) and Patlak graphical analysis for the FDG study to estimate flux (Ki) and delivery (K1) parameters. Quantification of flux and K1 shows lower bias and better precision for both radiotracers on the long AFOV scanner, especially at low doses. Dynamic imaging on a long AFOV system can be achieved for a greater range of injected doses, as low as 0.5-2 mCi depending on the sphere size and flux, compared to a standard AFOV scanner, while maintaining good kinetic parameter estimation.


Effects of the antiepileptic drug carbamazepine on human erythrocytes.
The structural effects of the antiepileptic drug carbamazepine (CBZ) on the human erythrocyte membrane and molecular models have been investigated in the present work. This report presents the following evidence that CBZ interacts with red cell membranes: (a) X-ray diffraction and fluorescence spectroscopy of phospholipid bilayers showed that CBZ perturbed a class of lipids found in the outer moiety of the erythrocyte membrane; (b) in isolated unsealed human erythrocytes (IUM) the drug induced a disordering effect on the polar head groups and acyl chains of the membrane lipid bilayer; (c) in scanning electron microscopy (SEM) studies on human erythrocytes the formation of echinocytes was observed, due to the preferential insertion of CBZ in the outer monolayer of the red cell membrane. The effects of the drug detected in the present work were observed at concentrations of the order of those currently appearing in serum when it is therapeutically administered. This is the first time that toxic effects of carbamazepine on the human erythrocyte membrane have been described.


Targeted genotype analyses of GWAS-derived lean body mass and handgrip strength-associated single-nucleotide polymorphisms in elite master athletes.
Recent large genome-wide association studies (GWAS) have independently identified a set of genetic loci associated with lean body mass (LBM) and handgrip strength (HGS). Evaluation of these candidate single-nucleotide polymorphisms (SNPs) may be useful to investigate genetic traits of populations at higher or lower risk of muscle dysfunction. As such, we investigated associations between six SNPs linked to LBM or HGS in a population of elite master athletes (MA) and age-matched controls as a representative population of older individuals with variable maintenance of muscle mass and function. Genomic DNA was isolated from buffy coat samples of 96 individuals [consisting of 48 MA (71 ± 6 yr, age-graded performance 83 ± 9%) and 48 older controls (75 ± 6 yr)]. SNP validation and sample genotyping were conducted using the tetra-primer amplification refractory mutation system (ARMS). For the three SNPs analyzed that were previously associated with LBM (FTO, IRS1, and ADAMTSL3), multinomial logistic regression revealed a significant association of the ADAMTSL3 genotype with %LBM (P < 0.01). For the three HGS-linked SNPs, neither GBF1 nor GLIS1 showed any association with HGS, but for TGFA, multinomial logistic regression revealed a significant association of genotype with HGS (P < 0.05). For ADAMTSL3, there was an enrichment of the effect allele in the MA (P < 0.05, Fisher's exact test). Collectively, of the six SNPs analyzed, ADAMTSL3 and TGFA showed significant associations with LBM and HGS, respectively. The functional relevance of the ADAMTSL3 SNP in body composition and of TGFA in strength may highlight a genetic component of the elite MA phenotype.


Incidence and aetiology of infantile spasms from 1960 to 1976: a population study in Finland.
This series of cases of infantile spasms comprised 107 children born between 1960 and 1976 in the county of Uusimaa, Finland. The incidence of the syndrome was 0.38 to 0.42/1000 live births and has remained almost unchanged during those years, although there have been changes in the size of different aetiological groups. The importance of prenatal and perinatal factors, and especially of neonatal hypoglycaemia, as causal factors has decreased, whereas the numbers of cases due to infections and malformations has increased. Compared with investigations in other countries, this Finnish series differs in the incidence of familial cases and congenital cytomegalovirus infection, and especially in the higher incidence of neonatal hypoglycaemia and the lower incidence of tuberous sclerosis.


Dichotic listening in children with serious language problems.
20 children with serious language problems (mainly expressive) were tested with the Dichotic Listening (DL) test for language laterality. 16 were right-handed and 4 left-handed. The dichotic test consisted of series of pairwise presentations of CVC-syllables with "target-syllables" that should be detected interspersed among "distractors." The child pointed to a sheet of paper on which a picture representing the targets (and distractors) was printed. In addition, the children were tested on several expressive and impressive language tests and on finger-tapping. Analysis showed an increased frequency of subjects with a left-ear advantage (LEA) and a reduced amplitude of the right-ear advantage (REA) for those subjects showing a right-ear advantage. Correlations with the language variables and with finger-tapping are presented and discussed.


Idiopathic adult colo-colonic intussusception: Case report and review of the literature.
Acute colonic intussusception occurring in the absence of organic cause is uncommon in adults. We report acute colonic intussusception in a 46-year-old female; clinical evidence of a palpable mass, abdominal pain and bloody mucoid stools appeared a few hours after hospital admission. Multislice CT-scan confirmed the clinical diagnosis and surgical exploration revealed right colonic obstruction caused by intussusception of the cecum into the ascending colon. Right hemicolectomy was performed and histopathological examination did not reveal any causative pathology. Intussusception remains a rare condition in adults, representing 1-5% of bowel obstruction and accounting for 0.003-0.02% of all hospital admissions. Intussusception occurs more frequently in the small (50-80%) than in the large bowel (12-50%). It is estimated that approximately 90% of intussusceptions in adults are secondary to an anatomical or pathological condition, of which more than half are malignant. Idiopathic cases are the exception in adults. The clinical presentation of adult intussusception differs considerably from the classic pediatric presentation of abdominal pain, palpable mass, and blood per rectum, which is rarely seen in adults. A pre-operative CT-scan showed a 10cm intussuscepted segment of right colon. Surgical resection was considered mandatory because of severe bowel obstruction, and the theoretical possibility of occult malignancy. This approach was vindicated by the presence of widespread ischemic lesions in the wall of the resected bowel, without any obvious lead point. There are few reports in the medical literature of acute colonic intussusception occurring in the absence of organic cause in adults.


Phosphorylation of β-catenin at serine 663 regulates its transcriptional activity.
β-Catenin, a component of Wnt signaling, plays a key role in colorectal carcinogenesis. The phosphorylation status of β-catenin determines its fate and affects its cellular function, and serine 675 (S675) was previously identified as a common target of p21-activated kinase 1 (PAK1) and protein kinase A. In the present study, we explored the PAK1-specific phosphorylation site(s) in β-catenin. Active PAK1 T423E but not inactive PAK1 K299R interacted with and phosphorylated β-catenin. Mutagenesis followed by a kinase assay revealed that PAK1 phosphorylated S663 in addition to S675, and an anti-phospho-β-catenin(S663) antibody detected the phosphorylation of S663 downstream of PAK1 in various human colon cancer cells. Furthermore, the Wnt3a-stimulated S663 phosphorylation was inhibited by the PAK1-specific inhibitor, IPA-3, but not by H-89 or LY294002. The non-phosphorylatable mutant forms of β-catenin, S663A, S675A and S663/675A, showed similar defects in their PAK1-induced TCF/LEF transactivation, whereas the phosphomimetic form of β-catenin, S663D, demonstrated a transcriptional activity that was comparable to that of β-catenin S675D and β-catenin S663D/S675D. Taken together, these results provide evidence that PAK1 specifically phosphorylates β-catenin at S663 and that this phosphorylation is essential for the PAK1-mediated transcriptional activation of β-catenin.


Conformal proton radiation therapy for pediatric low-grade astrocytomas.
To evaluate the safety and efficacy of proton radiation therapy (PRT) for intracranial low-grade astrocytomas, the authors analyzed the first 27 pediatric patients treated at Loma Linda University Medical Center (LLUMC). Between September 1991 and August 1997, 27 patients (13 female, 14 male) underwent fractionated proton radiation therapy for progressive or recurrent low-grade astrocytoma. Age at time of treatment ranged from 2 to 18 years (mean: 8.7 years). Tumors were located centrally (diencephalic) in 15 patients, in the cerebral and cerebellar hemispheres in seven patients, and in the brainstem in five patients. 25/27 patients (92%) were treated for progressive, unresectable, or residual disease following subtotal resection. Tissue diagnosis was available in 23/27 patients (85%). Four patients with optic pathway tumors were treated without histologic confirmation. Target doses between 50.4 and 63.0 CGE (Cobalt Gray Equivalent, mean: 55.2 CGE) were prescribed at 1.8 CGE per fraction, five treatments per week. At a mean follow-up period of 3.3 years (0.6-6.8 years), 6/27 patients experienced local failure (all located within the irradiated field), and 4/27 patients had died. By anatomic site these data translated into rates of local control and survival of 87% (13/15 patients) and 93% (14/15 patients) for central tumors, 71% (5/7 patients) and 86% (6/7 patients) for hemispheric tumors, and 60% (3/5 patients) and 60% (3/5 patients) for tumors located in the brainstem. Proton radiation therapy was generally well tolerated. All children with local control maintained their performance status. One child with associated neurofibromatosis, Type 1, developed Moyamoya disease. All six patients with optic pathway tumors and useful vision maintained or improved their visual status. This report on pediatric low-grade astrocytomas confirms proton radiation therapy as a safe and efficacious 3-D conformal treatment modality. Results are encouraging for central tumors as well as large optic pathway tumors, where dose conformity is of particular importance; yet it is difficult to achieve. Longer follow-up time is needed to fully evaluate the benefits of normal tissue sparing.


Isolated Lung Perfusion for Pulmonary Metastases.
Isolated lung perfusion (ILP) is a surgical technique developed to treat pulmonary metastases. During ILP, high-dose chemotherapy is delivered into the pulmonary vasculature, minimizing systemic exposure and delivering the chemotherapeutic agent directly to the lung. ILP has been studied extensively in a variety of animal models and in humans in phase I trials. The most frequently studied chemotherapeutic agents used in ILP are doxorubicin, 5-flurodeoxyuridine, tumor necrosis factor-α, paclitaxel, melphalan, gemcitabine, and cisplatin. Phase I clinical trials with ILP have shown that ILP can be safely performed in humans but with mixed clinical results and poor long-term survival.


Phenobarbital interactions with derivatized activated carbon surfaces.
The interactions between phenobarbital and activated carbon surfaces were studied in detail in this work. This was accomplished by utilizing different reagents to manipulate the surface polar functional group compositions of different activated carbons, and determining how those modifications changed phenobarbital adsorption. Oxidation of an activated carbon surface caused a systematic decrease in the basal carbon surface, resulting in a concurrent systematic decrease in the non-specific adsorption of phenobarbital. Even more interesting, it was shown for the first time that chemical reduction of some of the carbonyl-containing functional groups on the activated carbon surface caused a significant increase in the specific adsorption of phenobarbital without any significant effect on the non-specific adsorption. These results support the notion that the OH groups on activated carbon surfaces are the specific adsorption sites for phenobarbital from aqueous solutions, and that the basal carbon surface is the region where non-specific adsorption takes place.


Isolation of replicational cue elements from a library of bent DNAs of Aspergillus oryzae.
Two fragments that could function as replicational cue elements were isolated from a genomic DNA digest of Aspergillus oryzae on the basis of abnormal behavior in polyacrylamide gel electrophoresis. The vector used in this study contained a scaffold-associated region of the Drosophila melanogaster ftz gene to provide nuclear retention. Neither fragment contained a yeast ARS consensus sequence or an eukaryotic topoisomerase II binding sequence. One of the fragments showed sequence homology with the mitochondrial replication origin of Candida utilis and a portion of mitochondrial DNA of Aspergillus nidulans. This plasmid carrying the cue fragment could also replicate in HeLa and NIH3T3 cells.


Diagnostic Value of Gd-EOB-DTPA-Enhanced MRI for the Expression of Ki67 and Microvascular Density in Hepatocellular Carcinoma.
National Natural Science Foundation of China; Contract grant number: 81260214. Recent studies have highlighted the diagnostic value of Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI in small hepatocellular carcinoma (HCC). Ki67 and CD34 are histologic markers that reflect the proliferation of tumor cells and the microvascular density (MVD). To explore the diagnostic value of Gd-EOB-DTPA-enhanced MRI for Ki67 expression and MVD in HCC. Retrospective. In all, 180 patients with HCC. 3.0T, Gd-EOB-DTPA-enhanced T1 WI volumetric interpolated breath-hold examination (VIBE) axial fat suppression plain, and enhanced scanning. The T1 relaxation time (T1 rt) and signal intensity (SI) of the lesion were measured. The Ki67 expressions and MVD were evaluated by immunohistochemistry. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic efficacy of T1 rt for high Ki67 expression (≥50%) and high MVD (≥100). The T1 rt-20min, rrT1 rt-20min, and SI-hepatobiliary phase (SI-HBP) were strongly correlated with Ki67, the r values were 0.846, -0.765, and -0.760 (P < 0.05), respectively. There were moderate correlations with CD34, with r values -0.444, 0.336, and -0.463 (P < 0.05), respectively. The T1 rt-Pre, T1 rt-20min, SI-Pre, and SI-HBP were significantly different both between the high and low ki67 expression groups (P < 0.05) and between the high MVD and low MVD groups (P < 0.05). In the two groups the T1 rt-20min and SI-HBP was 800.06 ± 128.91 vs. 530.06 ± 139.29 (P < 0.05) and 122.29 ± 39.39 vs. 173.49 ± 46.15 (P < 0.05); T1 rt-20min was found to have high diagnostic efficiency for high ki67 expression (area under the curve [AUC], 0.937; P < 0.05) T1 rt-20min had moderate diagnostic value for high MVD (AUC, 0.716; P < 0.05). The T1 rt and SI of Gd-EOB-DTPA-enhanced MRI were correlated with Ki67 expression and MVD. T1 rt-20min has a high diagnostic value for high ki67 expression and high MVD in HCC tissues. 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1755-1763.


Healthy Sleepers Can Worsen Their Sleep by Wanting to Do so: The Effects of Intention on Objective and Subjective Sleep Parameters.
Sleep is regulated by homeostatic and circadian factors. In addition, psychological factors have a strong modulatory impact on our sleep, but the exact underlying mechanisms are still largely unknown. Here, we examined the role of intentions on subjective and objective sleep parameters. Young healthy sleepers were instructed to voluntarily either worsen or improve their sleep. We predicted that participants would be capable of worsening, but not improving, their sleep compared to a regular sleep condition. In addition, we predicted that the instruction to alter sleep would lead to a higher discrepancy between subjective and objective sleep variables. Twenty-two healthy students participated in one adaptation and three experimental nights. Polysomnography and subjective sleep parameters were measured during all four nights. Participants were instructed to sleep regularly ("neutral"), better ("good") or worse ("bad") than normal, in a counterbalanced order. The instruction to sleep "bad" increased objective sleep onset latency and the number of awakings during the night. The effects were stronger on subjective sleep variables, resulting in a higher sleep misperception in the "bad" condition as compared to the other two conditions. The instruction to sleep "good" did not improve sleep nor did it affect sleep misperception. We conclude that intention is sufficient to impair (but not improve) subjective and objective sleep quality and to increase sleep misperception in healthy young sleepers. Our results have important implications for the understanding of the impact of psychological factors on our sleep.


Imaging features of myxoid soft-tissue tumours.
Myxoid soft-tissue tumours are mesenchymal neoplasms, which are characterised by the production of abundant extracellular myxoid matrix. Imaging plays an important role in the diagnosis of these tumours as well as treatment planning. The imaging features as well as the clinical course for these lesions are highly variable, depending on both the anatomical location of the tumour and the histopathological subtype. This article, illustrated by histopathologically proven cases from our tertiary referral soft-tissue sarcoma centre, reviews the spectrum of imaging findings and characteristic signs seen with different types of benign and malignant myxoid soft-tissue neoplasms.


[Effect of ergot alkaloid derivatives on milk secretion in the immediate postpartum period].
30 women received an intramuscular injection of 0.2 mg of methylergobasine immediately after delivery and then 3 tablets of 1 mg of ergotamine tartrate per mouth daily for 6 days post-partum. 28 women received no treatment after delivery. The selection of the two groups was random. The treatment with rye ergot derivatives did not have a significant effect on the quantity of milk that the infant took, nor on the infant's weight gain in the 6 first days of life.


G-CuP: the effect of a forced oral glucose intake on alcohol craving and mesolimbic cue reactivity in alcohol dependence-study protocol of a randomized, double-blind, placebo-controlled crossover study.
Multiple studies indicate that a lower plasma level of the acetylated form of the appetite-regulating hormone ghrelin and higher plasma levels of insulin lead to a reduction in subjective alcohol craving and a reduced mesolimbic cue reactivity in functional magnetic resonance imaging (fMRI) when being exposed to alcohol-associated stimuli. The ghrelin level can physiologically be reduced by the induction of stomach distension and the ingestion of glucose or lipids. A total of 108 alcohol-dependent patients aged between 18 and 65 years are examined in the randomized, double-blind, placebo-controlled crossover study. After collecting demographic and psychometric data, participants take part in an alcohol exposure session. Afterwards, the participants go through the intervention condition (oral glucose intake) and the control condition (placebo intake) in a randomized order on two examination days. Blood samples are taken repeatedly (every 10 min) during the study course on both measuring days to determine changes in acetylated and total ghrelin and insulin plasma levels. In parallel, subjective alcohol craving after the glucose or placebo intake as the primary outcome is assessed using the Alcohol Urge Questionnaire (AUQ) and a visual analog scale (VAS). To examine the mesolimbic cue reactivity as the secondary outcome, a fMRI measurement is conducted while being exposed to alcohol-related stimuli. Appropriate statistical analysis will be used for the evaluation of the outcomes. If successful, the results of this study could offer alcohol-dependent patients a new potential option for acute short-term reduction of alcohol craving and thus prevent relapses and prolong periods of abstinence in the long term. German Clinical Trials Register DRKS00022419 (UTN: U1111-1278-9428). Retrospectively registered on September 15, 2020.


Design, synthesis, and biological evaluation of catecholamine vehicle for studying dopaminergic system.
Catecholamine mimetic EDTA-bis(tyramide) was synthesized and characterized by various spectroscopic techniques (NMR, mass spectroscopy) and λem 310 nm for the excitation at 270 nm. Molecular docking studies were performed with human serum albumin (PDB 1E78), showing binding pattern with amino acid residues Arg218, Arg222, and Lys444, identifies the ligand-human serum albumin interaction for the transportation affinity of the ligand at the specific site of the target. Subsequently, binding study with human serum albumin at λex = 350 nm found to be 5.847 × 10(4) m(-1) shows effective quenching effect. Additionally, to go more insight, acetylcholinesterase binding affinity was investigated, which shows 90% binding affinity for the 10 mm concentration. IC50 value was found 18.60 μm for MAO-B inhibition. Finally, EDTA-bis(tyramide) labeled with (99m) Tc to investigate its in vivo radiopharmaceutical efficiency having 97% binding affinity with 98% radiochemical purity. In vivo studies were carried out for (99m) Tc-EDTA-bis(tyramide) included blood kinetics showed a quick wash out from the circulation via renal route, and biodistribution revealed that maximum %ID/g was found in kidney at 1 h, and its scintigraphy image shows 3.96% brain uptake with respect to whole body.


Peptidylglycine alpha-amidating monooxygenase activity in spinal cord, dorsal roots, and dorsal root ganglia of Macaca fascicularis.
Several peptides synthesized by primary sensory neurons are alpha-amidated at the C-terminal residue, including vasoactive intestinal polypeptide, neurokinin A and substance P, which is also abundant in spinal cord. In pituitary and other tissues, the C-terminal amidation is catalyzed by peptidylglycine alpha-amidating monooxygenase (PAM). In the present study, soluble PAM activity in spinal cord and in primary sensory neurons is quantified and characterized as to cofactor and cosubstrate requirements and substrate specificity.


Phyllodes tumors of the breast: correlation of nucleolar organizer regions with histopathological malignancy grading, flow cytometric DNA analysis and clinical outcome.
To examine whether nucleolar organizer regions detected by argyrophilia (Ag-NOR counts) can be used as a prognostic indicator in phyllodes tumors of the breast, and to compare its usefulness with that of DNA flow cytometric analysis, 28 cases of breast phyllodes tumors (including 15 benign, two borderline and 11 malignant tumors) were subjected to Ag-NOR staining and counting as well as DNA flow cytometric analysis. S-phase fraction and DNA ploidy analysis showed useful trends for improving outcome predictions in malignant phyllodes tumors. However, high Ag-NOR counts were significant in predicting survival status (P = 0.013) and reached near statistical significance in predicting survival times (P = 0.07). In predicting survival status, results for Ag-NOR counts were significantly better than those for ploidy analysis (P = 0.02) and S-phase fraction (P < 0.01). Only S-phase fraction was significantly predictive of survival times (P = 0.025). It is concluded that Ag-NOR counts and DNA flow cytometric analysis, easily performed using paraffin sections, give information that can improve predictions made by histopathological classification. Ag-NOR counts are significant in predicting survival in the presence of histopathological features of malignancy.


Anti-PP1Pk and early abortion.
Anti-PP1Pk is found in the serum of individuals of phenotype p. Recurrent first trimester miscarriages have been reported in nearly 50 percent of mothers with the p phenotype. A comparative serologic study of three p phenotype mothers is reported. The proposita had three miscarriages while her two identical twin sisters had normal pregnancies. Following serum fractionation on DEAE-cellulose, serial agglutination with P1 and P2 erythrocytes indicated a possible association between IgG anti-P and the increased risk of abortion.


KAT7/HBO1/MYST2 Regulates CENP-A Chromatin Assembly by Antagonizing Suv39h1-Mediated Centromere Inactivation.
Centromere chromatin containing histone H3 variant CENP-A is required for accurate chromosome segregation as a foundation for kinetochore assembly. Human centromere chromatin assembles on a part of the long α-satellite (alphoid) DNA array, where it is flanked by pericentric heterochromatin. Heterochromatin spreads into adjacent chromatin and represses gene expression, and it can antagonize centromere function or CENP-A assembly. Here, we demonstrate an interaction between CENP-A assembly factor M18BP1 and acetyltransferase KAT7/HBO1/MYST2. Knocking out KAT7 in HeLa cells reduced centromeric CENP-A assembly. Mitotic chromosome misalignment and micronuclei formation increased in the knockout cells and were enhanced when the histone H3-K9 trimethylase Suv39h1 was overproduced. Tethering KAT7 to an ectopic alphoid DNA integration site removed heterochromatic H3K9me3 modification and was sufficient to stimulate new CENP-A or histone H3.3 assembly. Thus, KAT7-containing acetyltransferases associating with the Mis18 complex provides competence for histone turnover/exchange activity on alphoid DNA and prevents Suv39h1-mediated heterochromatin invasion into centromeres.


Selective Reductive Removal of Ester and Amide Groups from Arenes and Heteroarenes through Nickel-Catalyzed C-O and C-N Bond Activation.
An inexpensive nickel(II) catalyst and a hydrosilane were used for the efficient reductive defunctionalization of aryl and heteroaryl esters through a decarbonylative pathway. This versatile method could be used for the removal of ester and amide functional groups from various organic molecules. Moreover, a scale-up experiment and a synthetic application based on the use of a removable carboxylic acid directing group highlight the usefulness of this reaction.


Evaluation of the pharmacodynamic profile of commonly used intravenous vancomycin dosing schemes in patients on automated peritoneal dialysis.
The intent of this study was to evaluate the appropriateness of commonly used intravenous (iv) vancomycin dosing schemes in patients on automated peritoneal dialysis (APD) using population pharmacokinetic (PK) modelling and Monte Carlo simulation. Data from a single-dose PK study of 10 non-infected APD patients ≥18 years old were analysed. Patients received iv vancomycin (15 mg/kg) followed by three cycler-assisted APD dwells over 8 h, followed by two 8 h dwells. Serum and dialysate samples were collected over the entire 24 h. A three-compartment model was fitted to the data with BigNPAG. Monte Carlo simulation was used to determine the probability of achieving an AUC/MIC ratio of >400 in both the serum and the peritoneal cavity for a variety of iv vancomycin dosing schemes (1-2 g every 24-48 h). In the probability of target attainment (PTA) analyses, only 2 g of iv vancomycin every 24 h conferred >90% probability of achieving an AUC/MIC ratio of >400 for MIC values <2 mg/L in the serum. However, this dosing regimen resulted in average trough concentrations >20 mg/L. In the peritoneal cavity, no regimen yielded PTA ≥90% for MIC values ≥0.5 mg/L. Although expert guidelines suggest iv vancomycin may be an acceptable empirical therapy for patients on APD with infection, these analyses indicate that iv vancomycin may not be effective for peritonitis but may be a viable option for non-peritoneal infections with MIC values ≤1 mg/L.


Propofol effects on cerebellar long-term depression.
Propofol is an intravenously administered anesthetic that induces γ-aminobutyric acid-mediated inhibition in the central nervous system. It has been implicated in prolonged movement disorders. Since the cerebellum is important for motor coordination and learning, we investigated the potential effects of propofol on cerebellar circuitry. Using the whole-cell patch-clamp technique in Wister rat cerebellar slices, we demonstrated that propofol administration impaired long-term depression from the parallel fiber (PF) to Purkinje cell (PC) synapses (PF-LTD). Also, propofol reduced metabotropic glutamate receptor 1 (mGluR1)-mediated and group I mGluR agonist-induced slow currents in PCs. These results suggest that the propofol-induced PF-LTD impairment may be related to an alteration in mGluR1 signaling, which is essential to motor learning.


Clinical evaluation of five electronic root canal length measuring instruments.
A previous in vitro study has shown high accuracy, but no clinically significant differences in a group of five electronic root canal length measuring instruments. The purpose of this study was to evaluate and compare the performance of the same group of instruments under clinical conditions and to correlate their accuracy to radiographic estimates of canal length. Five electronic root canal length measuring instruments were used to measure the working length to the "apex" in 20 single-rooted teeth scheduled for extraction. After extraction, the actual canal length was measured visually to a point just within the apical foramen. This length was compared with instrument length as determined electronically. The accuracy of the instruments in determining canal measurement within +/- 0.5 mm from the apical foramen varied from 55 to 75%. The differences between the instruments were not statistically significant. On average, all of the instruments except for the Endocater gave canal length measurements that were beyond the apical foramen. The variability of the measurements, which was comparable to that of estimates of canal length from preoperative radiographs, indicated that radiographic verification of the working length is still desirable.


Development of a DNA microarray assay for rapid detection of fifteen bacterial pathogens in pneumonia.
The rapid identification of pathogenic bacteria is important for determining an appropriate antimicrobial therapy for pneumonia, but traditional bacterial culture is time-consuming and labourious. The aim of this study was to develop and evaluate a DNA microarray assay for the simultaneous detection of fifteen bacterial species directly from respiratory tract specimens in patients with pneumonia. These species included Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Mycoplasma pneumoniae, Enterococcus faecalis, Enterococcus faecium, Enterobacter cloacae, Stenotrophomonas maltophilia, Burkholderia cepacia, Legionella pneumophila and Chlamydia pneumoniae. The 16S rDNA genes and other specific genes of each pathogen were chosen as the amplification targets, amplified via multiplex polymerase chain reaction (PCR), and hybridized to oligonucleotide probes in a microarray. The DNA microarray detection limit was 103 copies/μL. Nineteen standard strains and 119 clinical isolates were correctly detected with our microarray, and 3 nontarget species from 4 clinical isolates were not detected. Additionally, bacterial pathogens were accurately identified when two or three bacterial targets were mixed together. Furthermore, the results for 99.4% (156/157) of clinical specimens were the same as those from a conventional assay. We developed a DNA microarray that could simultaneously detect various bacterial pathogens in pneumonia. The method described here has the potential to provide considerable labour and time savings due to its ability to screen for 15 bacterial pathogens simultaneously.


Recovery of third nerve palsy following surgical clipping of posterior communicating artery aneurysms.
The objective of the study was to identify the predictors of improved third cranial nerve (CN III) function in patients who underwent surgical clipping for posterior communicating artery (PComA) aneurysms with varying degrees of CN III palsy at presentation. We retrospectively evaluated the outcome of the CN III function in a series of 26 patients with CN III dysfunction due to PComA aneurysms that were treated by surgical clipping. CN III palsy was complete in 18 patients (69%) and partial in 8 patients (31%) at the time of admission. In 15 patients (58%), there was total improvement of CN III function. Partial improvement was noted in 5 patients (19%). Overall improvement (partial and total) of CN III function was observed in 20 (77%) of the 26 patients. The improvement in CN III function following early surgery (0-3 days) was 81.3% when compared to 75% when surgery was performed after 3 days. In univariate analysis, the only variable showing significant association with total improvement of CN III function was type of third nerve palsy at admission (complete vs partial) (P=.004). There was no statistical significant association between early surgery and improvement of CN III function (P=.722). In multivariate analysis, among all the factors, the type of third nerve palsy at presentation (complete and partial) was the significant predictor of the improved CN III function (P=.0038). Surgical clipping of the PComA aneurysm in patients with CN III palsy results in improvement of the CN III function in the majority of patients. The type of the CN III palsy at admission (complete/partial) is a significant predictor of complete improvement in CN III function.


The effect of axial traction during orotracheal intubation of the trauma victim with an unstable cervical spine.
Axial (in-line) traction is recommended as a stabilizing maneuver during orotracheal intubation of a trauma victim with a potential cervical spine injury. There are no published data demonstrating the safety of this technique in trauma patients with an unstable cervical spine. In our study, 17 victims of blunt traumatic arrest had radiographic analysis of the cervical spine during orotracheal intubation, with and without axial traction. Four (24%) had unstable injuries, which included a C6-7 fracture dislocation, a Hangman's fracture, and two atlanto-occipital dislocations. Axial traction during oral intubation in these victims resulted in a mean distraction at the fracture site of 7.75 mm. Axial traction produced 4 mm of posterior subluxation in the C6-7 fracture dislocation, demonstrating that axial traction alone may result in subluxation, as well as distraction. This depends on the direction of the traction force and integrity of surrounding tissues. We recommend that trauma patients requiring intubation prior to a complete examination and radiographic analysis of the cervical spine be nasotracheally intubated without axial traction, and that the head and neck be stabilized in the neutral position. If a contraindication to nasotracheal intubation exists, a cricothyroidotomy should be performed.


Novel splittable N-Tx/2N-Rx transceiver phased array to optimize both signal-to-noise ratio and transmit efficiency at 9.4T.
The goal of this study was to optimize signal-to-noise ratio (SNR) and parallel receive (Rx) performance of ultrahigh field (UHF) (≥7T) transceiver arrays without compromising their transmit (Tx) efficiency. UHF transceiver head phased arrays with a tight fit improve Tx efficiency in comparison with Tx-only arrays, which are usually larger so that Rx-only arrays can fit inside. However, having ≥16 elements inside a head transceiver array presents decoupling problems. Furthermore, the available number of Tx channels is limited. A prototype of a splittable transceiver phased array was constructed. The array consisted of four flat surface Tx loops positioned in two rows. Each loop could be split into two smaller overlapped Rx loops during reception. Experimental data demonstrated that both SNR and parallel reception performance improved substantially by doubling the number of Rx elements from four to eight. As a proof of concept, we developed and constructed a novel splittable transceiver phased array that allows doubling of the number of Rx elements while keeping both Tx and Rx elements at the same distance from the subject. Both Tx and Rx performance can be optimized at the same time using this method. Magn Reson Med 76:1621-1628, 2016. © 2015 International Society for Magnetic Resonance in Medicine.


Mineralocorticoid receptor blockade attenuates hyperandrogenic metabolic dysregulation in letrozole-induced PCOS rat model.
Polycystic ovarian syndrome (PCOS) is a metabolic syndrome associated with mineralocorticoid receptor (MR) activation, which causes infertility in women of reproductive age. Spironolactone (SPL) is a MR blocker with inconclusive effect in the treatment of PCOS. Therefore, the present study hypothesized that low dose SPL would ameliorate metabolic dysfunction associated with PCOS. Female Wistar rats (8-week-old) were divided into 3 groups namely: Control, SPL, Letrozole (LET)-treated and LET + SPL-treated groups. The control group was given vehicle (distilled water), SPL-treated group received 0.25 mg/kg, LET-treated group received 1 mg/kg of LET and LET + SPL-treated group received a combination of LET and SPL. The administrations were done by oral gavage for 21 days uninterruptedly. Biochemical parameters such as lipid profile, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), γ-glutamyl transferase (GGT), lactate dehydrogenase (LDH), testosterone, 17-β estradiol and glutathione peroxidase (GPx) were determined with appropriate assay methods. Letrozole-treated group had a significant increase in ovarian weight, plasma and ovarian triglycerides, MDA/TNF-α, GGT/LDH and plasma testosterone while it decreased plasma 17-β estradiol and plasma/ovarian high-density lipoproteins and GPx when compared with control group. In addition, histomorphological changes were observed in LET-treated group compared with control group. Nevertheless, administration of low dose SPL attenuated these perturbations. The present study therefore demonstrates that inhibition of mineralocorticoid receptor by low dose SPL ameliorates hyperandrogenic metabolic dysfunction in a rat model of PCOS. Therefore, low dose SPL is hereby suggested as a promising therapeutic agent in the management of PCOS.