Improving Children's Expressive Language and Auditory Comprehension Through Responsive Caregiving: Evidence from a Randomized Controlled Trial of a Strength-Based Video-Coaching Intervention.
Young children from low-SES backgrounds are at higher risk for delayed language development, likely due to differences in their home language environment and decreased opportunities for back and forth communicative exchange. Intervention strategies that encourage reciprocal caregiver-child interactions may effectively promote young children's language development and enhance optimal language outcomes. The Filming Interactions to Nurture Development (FIND) program is a brief strength-based video-coaching intervention designed to promote increased back and forth ("serve and return") interactions between caregivers and their children. The current study used data from a randomized controlled trial (RCT) to examine the effectiveness of the FIND program in improving auditory comprehension and expressive communication skills among children from low-SES backgrounds. The current study used a pretest-posttest design to evaluate intervention effects from an RCT with 91 low-SES families. Families with children aged 4 to 36 months old (41.8% female) were randomly assigned to an active control or FIND intervention group. Children's auditory comprehension and expressive communication were assessed using the Preschool Language Scales, Fifth Edition (PLS-5) during both pre- and post-intervention sessions. Children in the FIND intervention group showed significantly increased expressive communication skills and a non-significant increase in auditory comprehension skills across the intervention period. In contrast, children in the active control group showed non-significant changes in expressive communication and a statistically significant decline in auditory comprehension abilities between pre- and post-intervention assessments. All analyses controlled for sex, age, and home language. This study provides preliminary evidence that the FIND intervention promotes the development of expressive and receptive language skills among young children in high-stress, low-SES environments.


IR TrueFISP with a golden-ratio-based radial readout: fast quantification of T1, T2, and proton density.
A promising approach for the simultaneous quantification of relative proton density (M(0)), T(1), and T(2) is the inversion-recovery TrueFISP sequence, consisting of an inversion pulse followed by a series of balanced steady-state free precession acquisitions. Parameters can then be obtained from a mono-exponential fit to the series of images. However, a segmented acquisition is usually necessary, which increases the total acquisition time considerably. The goal of this study is to obtain M(0), T(1), and T(2) maps using a single-shot acquisition, with T(1) and T(2) measurements in brain that are consistent with the published literature, with a 20-fold speed improvement over the segmented approach, and at a clinically relevant spatial resolution. To this end, a single-shot inversion-recovery TrueFISP sequence was combined with a radial view-sharing technique. The parameters M(0), T(1), and T(2) were then obtained on a pixel-wise basis from a three fit parameter to the signal evolution. The accuracy of this method for quantifying these parameters is demonstrated in vivo. In addition, further corrections to the quantification necessary owing to other experimental factors, namely magnetization transfer and imperfect slice profiles, were developed. Including additional scans necessary for these corrections in the measurement protocol, the required scan time is increased from approximately 6 to 18-28 s per slice.


Monitoring transformation of two tropical lignocellulosics and their lignins after residence in Benin soils.
Thermally assisted Hydrolysis and Methylation (THM), and 2D-heteronuclear single quantum coherence nuclear magnetic resonance (2D HSQC NMR) spectroscopy were used to monitor the transformation of ramial chipped wood (RCW) from Gmelina arborea and Sarcocephalus latifolius, together with their organosolv lignins, following soil incubation in Benin (West Africa). Mesh litterbags containing RCW were buried in soils (10 cm depth) and were retrieved after 0, 6, 12 and 18 months of field incubation. Chemical analysis showed that total carbohydrate content decreased, while total lignin content increased as RCW decomposition progressed. Ash and mineral content of RCW increased significantly after 18 months of decomposition in soil. Significant N-enrichment of the RCW was determined following 18 months incubation in soils, reaching 2.6 and 1.9 times the initial N-content for G. arborea and S. latifolius. Results of THM showed that the S + G sum, corresponding to lignins, increased with RCW residence time in the soils, in contrast to the response of compounds derived from carbohydrates, the sum of which decreased. Remarkably, lignin interunit linkages, most notably β-O-4' aryl ethers, β-β' resinol, β-5' phenylcoumaran and p-PCA p-coumarate, survived after 18 months in the soil, despite their gradual decrease over the duration of the experiment.


Rat corneal endothelial cell migration during wound repair on the basement membrane depends more on the PI-3K pathway than the cdc-42 pathway or actin stress fibers.
Following a central transcorneal circular freeze injury, organ-cultured rat corneal endothelial cells surrounding the wound reorganize peripheral actin bands into stress fibers and migrate individually into the wound. To ascertain the significance of this rearrangement relative to morphological changes accompanying migration and wound repair, some tissues were incubated overnight in 4 μM TRITC-conjugated phalloidin to stabilize actin and prevent its reorganization. After a freeze injury to the endothelium tissues were histologically observed at 24 h post-wounding and demonstrated that despite a lack of actin organization, cells responding to the injury appeared morphologically similar to their control counterparts. Tissues cultivated in the presence of either cytochalasin B (CB), soybean agglutinin (SBA), or fluorouracil (FU) and also exhibited actin cytoskeletal disruption. Under these conditions, migration continued despite the absence of detectable stress fibers. For SBA-, CB-, and FU-treated tissues, wound repair did not significantly differ from control preparations although FU-treated tissues showed a slower repair. Electron micrographs confirmed an absence of stress fibers in migrating cells treated with any of these agents. Tissues were also treated with ML 141 and EY294002 to inhibit the cdc-42 and PI-3K pathways, respectively. While cell movement still occurred in the presence of ML 141, migration into the wound was greatly restricted in the presence of EY294002. These results indicate that rat corneal endothelial cell movement in situ does not require actin reorganization into stress fibers, but the functioning of the PI-3K pathway is indispensable for their migration along the basement membrane during wound repair.


Efficacy of selamectin in the treatment and prevention of flea (Ctenocephalides felis felis) infestations on dogs and cats housed in simulated home environments.
The efficacy of selamectin, a novel avermectin, in protecting dogs and cats against experimentally induced environmental flea (Ctenocephalides felis felis) infestations, was evaluated in a series of controlled and masked studies. Purpose-bred shorthaired cats and Beagles were randomly allocated to treatment with either selamectin at a minimum dosage of 6mgkg(-1) of body weight in the commercial formulation or the negative control treatment (vehicle only), and housed in controlled simulated home environments capable of supporting the flea life cycle. Day 0 was defined as the first day of treatment. Treatments were administered topically in a single spot on the skin at the base of the neck in front of the scapulae. In environmental challenge studies, which were designed to evaluate the efficacy of selamectin in the treatment and control of established flea infestations, dogs and cats were each infested with 100 fleas on days -28 and -21 and placed in carpeted rooms in order to establish high levels of active flea infestation prior to day 0. Treatments were administered monthly for 3 months. Flea comb counts were performed on days 14, 29, 44, 59, 74, and 90. Reductions in geometric mean flea comb counts for selamectin, compared with vehicle, were >99% from day 14 onwards for dogs, and >92% on day 29 and >99% on days 44, 59, 74, and 90 for cats (P=0.0001). In prevention of environmental infestation studies, dogs and cats were placed in environments capable of supporting flea infestations and given monthly treatments for 2 months, commencing on day 0. Animals were infested with 100 fleas on days 1 and 7, and flea comb counts were performed on days 29, 44, and 60. Reductions in geometric mean flea comb counts for selamectin, compared with vehicle, were >99% on days 29, 44, and 60 (P=0.0001) for dogs and cats. Monthly administration of selamectin to dogs and cats housed in environments highly suited to completion of the flea life cycle was shown to be highly effective in the treatment and prevention of flea infestations, without the need for supplementary environmental control measures.


[Basal metabolism of an isolated rat heart preparation].
Estimation of the basic metabolism in isolated preparation of the rat heart by means of extrapolation of partial regression of the total energy expenditure by the heart on cardiac effort index at constant oxygen supply of the preparation, revealed on the average 72% of the total energy expenditure by the working preparation. Estimation of the same parameter by means of measuring the heart oxygen consumption after heart arrest with potassium, at the same level of oxygen supply, revealed on the average 49% of the mean total energy expenditure by the working preparation. The level of oxygen supply appears to have a major significance for the estimation of the heart basic metabolism.


Study on Components with Anti-Neuroinflammatory Activities from Caragana microphylla Lam.
Caragana microphylla Lam., is a perennial herb in the genus Caragana in the Fabaceae family. Two undescribed triterpenoid saponins (1-2), along with thirty-five known components (3-37) were obtained from the roots of C. microphylla Lam. These compounds were identified using physicochemical analyses and various spectroscopic methods. The anti-neuroinflammatory activities were evaluated by measuring the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced BV-2 microglial cells. Compared with positive control minocycline, compounds 10, 19, and 28 exhibited significant effects with IC50 values of 14.04, 19.35 and 10.20 μM, respectively.


Early detection of bronchial lesions using newly developed videoendoscopy-based autofluorescence bronchoscopy.
The combination of white light and autofluorescence bronchoscopy has been reported to show better sensitivity in detecting dysplasia and cancer of the bronchus than white light alone. However, fiberoptic bronchoscopy has been replaced by videoendoscopy at most leading facilities for over a decade. To avoid interruption of the videoendoscopy examination to perform fiberscopy-based autofluorescence examination as well as enhancing the sensitivity of intraepithelial lesions, autofluorescence diagnosis system integrated into a videoendoscope (SAFE 3000, Pentax, Tokyo) was created. A total of 154 consecutive patients were studied using this system, containing 83 known or suspected lung cancer cases, 46 of the cases with abnormal sputum cytology findings, 10 follow up cases following lung cancer operations, and 15 heavy smokers with respiratory symptoms. Abnormal findings were recognized by white light and/or SAFE 3000 at 166 sites and biopsies were taken to evaluate the relationship between endoscopic findings and pathology results. The sensitivity of the system for CIS+dysplasia was 65% in white light and 90% in SAFE. This videoendoscopy-based autofluorescence system had significantly higher sensitivity for intraepithelial lesions than white light videoendoscopy alone.


Catecholamine secreting tumor of the glomus jugulare.
A case of endocrinologically active glomus jugulare is presented. The localization within the tumor of the catecholamine hyperproduction was demonstrated by selective venous sampling from the vena jugularis externa draining the tumor. The norepinephrine/epinephrine ratio was high and of the same order in blood, urine and cerebrospinal fluid. Bioassay showed high levels of intratumoral norepinephrine and epinephrine. The ways of treatment and their influence on the catecholamines are briefly discussed. In every phaeochromocytoma-like syndrome both the existence of catecholamine hyperproduction and the anatomical site of this hypersecretion have to be precisely documented in order to define the correct treatment to be applied.


Impact of the calcium concentration on the efficacy of phage phiIPLA-RODI, LysRODIΔAmi and nisin for the elimination of Staphylococcus aureus during lab-scale cheese production.
Staphylococcus aureus is a Gram-positive human opportunistic pathogen that may also cause food poisoning because of the ability of some strains to produce heat stable enterotoxins that can persist in food even after the pathogen is successfully eliminated. In this context, biopreservation may be a forward-looking strategy to help eliminate staphylococcal contamination in dairy products by using natural compounds. However, these antimicrobials exhibit individual limitations that may be overcome by combining them. This work investigates the combination of a virulent bacteriophage, phiIPLA-RODI, a phage-derived engineered lytic protein, LysRODIΔAmi, and the bacteriocin nisin for the elimination of S. aureus during lab-scale cheese production at two CaCl2 concentrations (0.2 % and 0.02 %), and subsequent storage at two different temperatures (4 °C and 12 °C). In most of the assayed conditions, our results demonstrate that the combined action of the antimicrobials led to a greater reduction of the pathogen population than the compounds individually, albeit this effect was additive and not synergistic. However, our results did show synergy between the three antimicrobials for reducing the bacterial load after 14 days of storage at 12 °C, temperature at which there is growth of the S. aureus population. Additionally, we tested the impact of the calcium concentration on the activity of the combination treatment and observed that higher CaCl2 levels led to a notable increase in endolysin activity that allowed the utilization of approximately 10-times less protein to attain the same efficacy. Overall, our data show that the combination of LysRODIΔAmi with nisin and/or phage phiIPLA-RODI, and an increase in the calcium concentration are successful strategies to decrease the amount of protein required for the control of S. aureus contamination in the dairy sector with a low potential for resistance selection, thereby reducing costs.


Telomeric fusion as a mechanism for the loss of 1p in meningioma.
Characteristic cytogenetic aberrations are found in the various histopathological designations of meningioma. These aberrations range from the loss of 22q in histologically benign tumors to complex hypodiploid karyotypes in atypical and malignant tumors. This progression is characterized by increasing chromosome loss and instability, with a critical step being the loss of 1p. We report a detailed cytogenetic investigation of chromosome aberrations in a series of 88 meningiomas using Giemsa banding and multicolor spectral karyotyping (SKY). Clonal chromosome aberrations were identified in 46 (52%) tumors by G banding. Thirty-five tumors showing complex chromosome aberrations not fully characterized by G banding were subsequently reanalyzed by SKY. The SKY technique refined the G-band findings in 18 (51%) of the tumors on which it was applied. The most common features of cytogenetic progression in the complex karyotypes were chromosome arm-specific losses relating to the formation of deletions and dicentric chromosomes involving 1p. Part or all of 1p was lost in 19 tumors. Five tumors showed evidence for the loss of 1p in a progressive step-wise series of telomeric fusions involving the formation of unstable intermediates. Five recurring dicentric chromosomes were identified, including dic (1;11)(p11;p11), dic(1;12)(p12 approximately p13;p11), dic(1;22)(p11;q12 approximately q13), dic(7;19)(p11;p11), and dic(19;22)(p11 approximately p13;q11 approximately q13). These findings provide evidence that telomeric fusions play a role in the formation of clonal deletions, dicentrics, and unbalanced translocations of 1p. The loss of 1p has possible diagnostic and prognostic implications in the management of meningioma.


Synthesis and cellular characterization of novel isoxazolo- and thiazolohydrazinylidene-chroman-2,4-diones on cancer and non-cancer cell growth and death.
Coumarins are extensively studied anticoagulants that exert additional effects such as anticancerogenic and even anti-inflammatory. In order to find new drugs with anticancer activities, we report here the synthesis and the structural analysis of new coumarin derivatives which combine the coumarin core and five member heterocycles in hydrazinylidene-chroman-2,4-diones. The derivatives were prepared by derivatization of the appropriate heterocyclic amines which were used as electrophiles to attack the coumarin ring. The structures were characterized by spectroscopic techniques including IR, NMR, 2D-NMR and MS. These derivatives were further characterized especially in terms of a potential cytotoxic and apoptogenic effect in several cancer cell lines including the breast and prostate cancer cell lines MCF-7, MDA-MB-231, PC-3, LNCaP, and the monocytic leukemia cell line U937. Cell viability was determined after 48 h and 72 h of treatment with the novel compounds by MTT assay and the 50% inhibitory concentrations (EC50 values) were determined. Out of the 8 novel compounds screened for reduced cell viability, 4c, 4d and 4e were found to be the most promising and effective ones having EC50 values that were several fold reduced when compared to the reference substance 4-hydroxycoumarin. However, the effects were cancer cell line dependent. The breast cancer MDA-MB-231 cells, the prostate cancer LNCaP cells, and U937 cells were most sensitive, MCF-7 cells were less sensitive, and PC-3 cells were more resistant. Reduced cell viability was accompanied by increased apoptosis as shown by PARP-1 cleavage and reduced activity of the survival protein kinase Akt. In summary, this study has identified three novel coumarin derivatives that in comparison to 4-hydroxycoumarin have a higher efficiency to reduce cancer cell viability and trigger apoptosis and therefore may represent interesting novel drug candidates.


Characterization of glucansucrase and dextran from Weissella sp. TN610 with potential as safe food additives.
Pear-derived Weissella sp. TN610 produced extracellular glycosyltransferase activity responsible for the synthesis of soluble exopolysaccharide from sucrose. Acid and dextranase-catalyzed hydrolysis revealed that the synthesized polymer was a glucan. According to (1)H and (13)C NMR analysis, the glucan produced by TN610 was a linear dextran made of 96% α-(1→6) and 4% α-(1→3) linkages. Zymogram analysis confirmed the presence of a unique glucansucrase of approximately 180 kDa in the cell-free supernatant from TN610. The crude enzyme, optimally active at 37°C and pH 5, has promising potential for application as a food additive since it catalyzes dextran synthesis in sucrose-supplemented milk, allowing its solidification. A 4257-bp product corresponding to the mature glucansucrase gene was amplified by PCR from TN610. It encoded a polypeptide of 1418 residues having a calculated molecular mass of 156.089 kDa and exhibiting 96% and 95% identity with glucansucrases from Lactobacillus fermentum Kg3 and Weissella cibaria CMU, respectively.


Discovery of new cinnamic derivatives as anti-inflammatory agents for treating acute lung injury in mice.
The blockade of the overexpression of pro-inflammatory cytokines by anti-inflammatory natural products has been proven therapeutically beneficial in the treatment of acute lung injury (ALI). Given the fact that cinnamic acid has been proven to have significant anti-inflammatory activity, we selected it as a promising lead compound to develop more effective analogs in treating ALI. Learning from the symmetric structure of curcumin, 32 new symmetric cinnamic derivatives were designed, synthesized, and evaluated for their anti-inflammatory activity. Among them, 6h not only displayed a remarkable inhibitory activity in vitro (85.9% and 65.7% for IL-6 and TNF-α, respectively) without cytotoxicity but also possessed chemical structure stability. Furthermore, an in vivo study in mice revealed that the administration of 6h significantly attenuated lipopolysaccharide-induced ALI, providing new lead structures for the development of anti-inflammatory drugs for the treatment of ALI.


Sex differences in lectin-induced interleukin-2 synthesis in aging rats.
Several aspects of T cell-mediated immune responses decline with age, but it is not known how gender affects this decline. Using 3- and 26-month-old male and female Fischer 344 rats, we examined the effects of sex and age on four different immune events that normally decline during aging: antibody synthesis to a T-dependent antigen, lectin-induced proliferative responses, IL-2 synthesis, and natural killer activity. We found that all these responses decreased with age. Spleen cells from aged females had higher spontaneous, phytohemagglutinin (PHA), and concanavalin A (Con A)-induced proliferative responses, and a two-fold increase in IL-2 synthesis than aged males, although no differences in these responses were evident between young males and females. Both natural killer (NK) activity and the ability to generate plaque-forming cells to sheep erythrocytes (SRBC) declined with age, but there were no differences between males and females for these responses in either age group. These data indicate that sex-associated differences in IL-2 synthesis and spontaneous and lectin-induced proliferative responses that are not detected in young animals become evident with advancing age.


Community structures and comparison of nosZ and 16S rRNA genes from culturable denitrifying bacteria.
The objectives of this study were (i) to isolate and characterize of cultivable denitrifying bacteria using classic microbiological and molecular methods, (ii) to compare of 16S rRNA and nosZ genes as molecular markers, (iii) to determine bacterial community structure and diversity in soil samples using single-strand conformation polymorphism (SSCP) analysis. In this study, 49 bacterial isolates were cultivated and phylogenetic analyses grouped them into two phyla: Proteobacteria (37 species) and Firmicutes (12 species). Our study showed that the nosZ functional gen could be used to identify denitrifying bacteria abundance in environment but could not be used to identify pure bacterial cultures. In addition, the bacterial community structure showed significant differences among the various soil types. Phylogenetic analysis of community structure indicated that 51 clones could be divided into 2 phylotypes. Uncultured bacteria (80.4%) and Gammaproteobacteria (19.6%) were the dominant components of the soil bacterial community. For 16S rRNA, PCR products of 49 bacteria were obtained with 27F-1492R primer pairs. For nosZ, PCR products were obtained with primers 1F-1R (259 bp), 2F-2R (267 bp), and F-1622R (453 bp) of 39 bacteria that the single nosZ band provided on the agarose gel. The bacterial 16S rRNA gene clone library was dominated by Gammaproteobacteria and Bacilli. The nosZ clone sequences did not represent the bacteria from which they were obtained but were found to be closer to the environmental clones. Our study showed that the nosZ functional gene could be used to identify denitrification abundance in environment but could not be used to identify pure bacterial cultures. It was also found that the nosZ sequences showed uncultured denitrifier species.


National scale of neonatal CPAP to district hospitals in Malawi improves survival for neonates weighing between 1.0 and 1.3 kg.
To determine whether a national quality improvement programme implementing continuous positive airway pressure (CPAP) at government hospitals in Malawi improved outcomes for neonates prioritised by an algorithm recommending early CPAP for infants weighing 1.0-1.3 kg (the 50th percentile weight at 30 weeks' gestation). The analysis includes neonates admitted with respiratory illness for 5.5 months before CPAP was introduced (baseline period) and for 15 months immediately after CPAP was implemented (implementation period). A follow-up data analysis was completed for neonates treated with CPAP for a further 11 months. Neonates with admission weights of 1.0-1.3 kg before (106 neonates treated with nasal oxygen) and after implementation of CPAP (153 neonates treated with nasal oxygen, 103 neonates treated with CPAP) in the newborn wards at Malawi government district hospitals. Follow-up analysis included 87 neonates treated with CPAP. Neonatal CPAP. We assessed survival to discharge at 23 government district hospitals with no significant differences in transfer rates before and after implementation of CPAP. Survival improved for neonates with admission weights from 1.0 to 1.3 kg treated with CPAP (30.1%) as compared with neonates of the same weight band treated with oxygen during the baseline (17.9%) and implementation (18.3%) periods. There was no significant difference in survival for neonates treated with CPAP during the implementation and follow-up periods (30.1% vs 28.7%). Survival for neonates weighing 1.0-1.3 kg significantly increased with a nurse-led CPAP service in a low-resource setting and improvements were sustained during follow-up.


[Experimental studies on the domestic pig about reconstruction of the injured organ of continence].
In 12 domestic pigs, body weight ranging between 30 and 40 kg at operation, under general anesthesia the continence organ was paracoccygeally dissected on one side, and in 6 other animals bilaterally, and immediately thereafter reconstructed. The reconstruction was done paying regard to the fascial skeleton. In all cases the wounds healed primarily. The functional results were good, incontinence was not observed.


Elementary steps of the (Na+ + K+)-ATPase mechanism, studied with formycin nucleotides.
1. Formycin triphosphate (FTP), a fluorescent analogue of ATP, is a substrate for (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 220.127.116.11), with properties similar to those of ATP. 2. FTP and formycin diphosphate (FDP) bind to the enzyme with high affinity and, on binding, the nucleotide fluorescence is enhanced 3-4-fold. It is therefore possible, with a stopped-flow fluorimeter, to measure the rates of binding and release of FTP and FDP under conditions in which turnover does not occur. 3. When the enzyme-FTP complex is exposed to conditions permitting turnover (Mg2+, Na+ +/- K+), changes in fluorescence occur which can be explained by supposing that they reflect the interconversion of states with or without bound nucleotides. A rapid fall in fluorescence, that we attribute to the rapid release of FDP from newly phosphorylated enzyme, is followed by a steady state in which low fluorescence suggests that little nucleotide is bound. Eventually, exhaustion of FTP allows rebinding of FDP to the enzyme, which is signalled by a rise in fluorescence. 4. The estimated rate of FDP release from newly formed phosphoenzyme is unaffected by the presence of K+ (0-2 mM) or the concentration of FTP (1-20 micron). 5. Experiments with [gamma-32P]FTP show that about 1 mol of 32P is incorporated per mol of enzyme. The rate of phosphorylation of the enzyme by [gamma-32P]FTP has been measured with a rapid-mixing-and-quenching apparatus. 6. Kinetic data from the fluorescence and phosphorylation experiments show that the behaviour of the enzyme, at least at the low nucleotide concentrations employed, is consistent with the Albers-Post model, and is difficult to reconcile with models in which K+ acts at or before the step in which FDP is released during turnover.


Causes of mortality in individuals with tuberous sclerosis complex.
The causes of death in patients with tuberous sclerosis complex (TSC) have rarely been studied, with only one published account, which was reported from the Mayo Clinic in 1991. We aimed to investigate mortality in a large cohort of patients with TSC from one of two national referral clinics in the UK. We identified 284 patients who attended Bath TSC clinic between 1981 and 2015, and ascertained causes of death by reviewing medical records, death certificates, and postmortem reports. Sixteen patients died from complications of TSC: eight from TSC kidney diseases; four from sudden unexpected death in epilepsy (SUDEP); two from lymphangioleiomyomatosis; one from a subependymal giant cell astrocytoma; and one from a pancreatic malignancy. The median age of death was 33 years (interquartile range [IQR] 26-46). Mortality was significantly more common in patients with learning disabilities than in those without (13/135 [9%] vs 3/131 [2%]; two-tailed Fisher exact test p=0.020). Renal disease is a major cause of mortality in TSC. Lifelong surveillance and early intervention is warranted. SUDEP is also an important cause of mortality. Patients with learning disabilities are at significantly greater risk of early mortality and this implies the need for greater vigilance for TSC-related complications in this group. Female patients are vulnerable to pulmonary and renal disease. Pancreatic lesions are a rare but potentially treatable cause of mortality.


Effects of lidocaine on the function of immunocompetent cells. I. In vitro exposure of mouse spleen lymphocytes and peritoneal macrophages.
In vitro exposure of mouse lymphocytes and macrophages for 24 h to noncytotoxic doses of lidocaine (10(-4) to 10(-6)M) resulted in inhibition of random macrophage motility and in an interference with the production of macrophage migration inhibitory factor or with its interaction with the cell surface. The effects of lidocaine, membrane-stabilizing local anesthetic, were related to its concentration in the medium and to its ability to interact with the cell surface and cause changes in the ionic configuration of the plasma membrane. The drug conferred permanent changes on the surface of lymphocytes at all concentrations tested, but changes in the surface of macrophages induced by 10(-5) and 10(-6)M lidocaine were reversible. The presence of noncytotoxic doses of lidocaine in the cellular environment resulted in significant changes in cellular functions that appeared to be related to the ability of the drug to interact with cell membranes in a manner determined by the specific properties of the cell.


Analysis of Multidrug Transporter in Living Cells. Inhibition of P-glycoprotein-mediated Efflux of Anthracyclines by Ionophores.
One of the major obstacles of chemotherapy is that, after repeated treatments, cellular resistance to the drug appears. The problem is that the tumor cells become resistant not only to the drugs which have been used during the treatment but also to other drugs which are structurally and functionally unrelated. This is termed 'multidrug resistance' (MDR). MDR is frequently associated with decreased drug accumulation resulting from enhanced drug efflux. This is correlated with the presence of a membrane protein, P-glycoprotein, which pumps a wide variety of drugs out of cells thus reducing their toxicity. The search for molecules able to reverse MDR is very important. We here report that mobile ionophores such as valinomycin, nonactin, nigericin, monensin, calcimycin, lasalocid inhibit the efflux of anthracycline by P-glycoprotein whereas, channel-forming ionophores such as gramicidin do not. Cyclosporin which is also a strong Ca(2+) chelating agent also inhibits the P-glycoprotein-mediated efflux of anthracycline.


Beyond the cyclopropyl ring formation: fungal Aj_EasH catalyzes asymmetric hydroxylation of ergot alkaloids.
Ergot alkaloids (EAs) are among the most important bioactive natural products. FeII/α-ketoglutarate-dependent dioxygenase Aj_EasH from Aspergillus japonicus is responsible for the formation of the cyclopropyl ring of the ergot alkaloid (EA) cycloclavine (4). Herein we reconstituted the biosynthesis of 4 in vitro from prechanoclavine (1) for the first time. Additionally, an unexpected activity of asymmetric hydroxylation at the C-4 position of EA compound festuclavine (5) for Aj_EasH was revealed. Furthermore, Aj_EasH also catalyzes the hydroxylation of two more EAs 9,10-dihydrolysergol (6) and elymoclavine (7). Thus, our results proved that Aj_EasH is a promiscuous and bimodal dioxygenase that catalyzes both the formation of cyclopropyl ring in 4 and the asymmetric hydroxylation of EAs. Molecular docking (MD) revealed the substrate-binding mode as well as the catalytic mechanism of asymmetric hydroxylation, suggesting more EAs could potentially be recognized and hydroxylated by Aj_EasH. Overall, the newly discovered activity empowered Aj_EasH with great potential for producing more diverse and bioactive EA derivatives. KEY POINTS: • Aj_EasH was revealed to be a promiscuous and bimodal FeII/α-ketoglutarate-dependent dioxygenase. • Aj_EasH converted festuclavine, 9,10-dihydrolysergol, and elymoclavine to their hydroxylated derivatives. • The catalytic mechanism of Aj_EasH for hydroxylation was analyzed by molecular docking.


Sodium-losing nephropathy.
We studied prospectively 18 patients with sodium-losing nephropathy. In 12 patients (66.7 per cent) the sodium-losing nephropathy was owing to obstructions, challenging the hitherto existing concept that the most common cause of the condition is pyelonephritis. The diagnosis of sodium-losing nephropathy is important in urological practice since sodium repletion in these cases shortens significantly the hospitalization and preoperative waiting time.


Switchable Synthesis of Aryl Sulfones and Sulfoxides through Solvent-Promoted Oxidation of Sulfides with O2/Air.
A practical and switchable method for the synthesis of aryl sulfones and sulfoxides via sulfide oxidation was developed. The chemoselectivities of products were simply controlled by reaction temperature using O2/air as the terminal oxidant and oxygen source. The broad substrate scope, easy realization of gram-scale production, and the simplification of a sulfide oxidation system render the strategy attractive and valuable.


Generation of a cholesterol-independent, non-GS NS0 cell line through chemical treatment and application for high titer antibody production.
NS0 cells require exogenous cholesterol for growth. The non-glutamine synthetase (GS) cholesterol-dependent NS0 host was treated with 5-azacytidine (5azaC), a demethylation drug, and adapted to grow in cholesterol-free, chemically defined medium. Within 7 weeks, a stable, cholesterol-independent NS0 host (NS0.CF) was obtained. The new NS0.CF host, as well as the original cholesterol auxotroph host, was transfected with the same mAb expression plasmid, and the top producing clone from both hosts were compared side-by-side in the enhanced platform fed-batch cultures using chemically defined media. The NS0.CF derived clone significantly out-performed the cholesterol-dependent clone, with titer reaching 4.5 g/L versus 3.0 g/L, respectively, mainly due to higher specific productivity, while key product quality attributes remained comparable. This work demonstrated an effective and rapid approach to generate a cholesterol-independent NS0 host, and its application in recombinant protein production.


Developmental exposure to intranasal vasopressin impacts adult prairie vole spatial memory.
Spatial memory is critical for many tasks necessary for survival (i.e., locating mates and food resources). The two mammalian nonapeptides arginine vasopressin (AVP) and oxytocin (OT) are mechanistically important in modulating memory ability, albeit in contrasting ways. In general, AVP facilitates memory consolidation and retrieval while OT is an amnesic. Although AVP and OT are known to have these memory effects, past work has focused on their impact in social memory with little research on their effects on spatial memory. In this experiment, we tested the impact of AVP and OT on spatial memory as determined by performance in the Morris water maze (MWM). We administered doses of AVP, OT, or saline (a control) intranasally to male prairie voles (Microtus ochrogaster), a species whose spatial memory is hypothesized to impact their mating tactics. We also investigated if acute doses (given immediately prior to the memory trial in the MWM) and chronic doses (given daily during adolescence) had differing impacts on spatial cognition. We found that chronic intranasal administration of AVP during post-wean development improved spatial memory performance. In contrast, both chronic and acute administration of OT and acute administration of AVP had no impact on spatial memory. These results together suggest that 1) chronic exposure to AVP has organizational effects on spatial memory in the prairie vole, and 2) acute administration of nonapeptides does not impact the retrieval of spatial memories.


Proposed diagnostic volumetric bone mineral density thresholds for osteoporosis and osteopenia at the cervicothoracic spine in correlation to the lumbar spine.
To determine the correlation between cervicothoracic and lumbar volumetric bone mineral density (vBMD) in an average cohort of adults and to identify specific diagnostic thresholds for the cervicothoracic spine on the individual subject level. In this HIPPA-compliant study, we retrospectively included 260 patients (59.7 ± 18.3 years, 105 women), who received a contrast-enhanced or non-contrast-enhanced CT scan. vBMD was extracted using an automated pipeline ( https://anduin.bonescreen.de ). The association of vBMD between each vertebra spanning C2-T12 and the averaged values at the lumbar spine (L1-L3) was analyzed before and after semiquantitative assessment of fracture status and degeneration, and respective vertebra-specific cut-off values for osteoporosis were calculated using linear regression. In both women and men, trabecular vBMD decreased with age in the cervical, thoracic, and lumbar regions. vBMD values of cervicothoracic vertebrae showed strong correlations with lumbar vertebrae (L1-L3), with a median Pearson value of r = 0.87 (range: rC2 = 0.76 to rT12 = 0.96). The correlation coefficients were significantly lower (p < 0.0001) without excluding fractured and degenerated vertebrae, median r = 0.82 (range: rC2 = 0.69 to rT12 = 0.93). Respective cut-off values for osteoporosis peaked at C4 (209.2 mg/ml) and decreased to 83.8 mg/ml at T12. Our data show a high correlation between clinically used mean L1-L3 values and vBMD values elsewhere in the spine, independent of age. The proposed cut-off values for the cervicothoracic spine therefore may allow the determination of low bone mass even in clinical cases where only parts of the spine are imaged. vBMD of all cervicothoracic vertebrae showed strong correlation with lumbar vertebrae (L1-L3), with a median Pearson's correlation coefficient of r = 0.87 (range: rC2 = 0.76 to rT12 = 0.96). The correlation coefficients were significantly lower (p < 0.0001) without excluding fractured and moderate to severely degenerated vertebrae, median r = 0.82 (range: rC2 = 0.69 to rT12 = 0.93). We postulate that trabecular vBMD < 200 mg/ml for the cervical spine and < 100 mg/ml for the thoracic spine are strong indicators of osteoporosis, similar to < 80 mg/ml at the lumbar spine.


Value of Anti-Vascular Endothelial Growth Factor Gene Therapy for Neovascular Age-Related Macular Degeneration.
To use discounted cash flow (DCF) analysis to estimate the value creation associated with anti-vascular endothelial growth factor (VEGF) genetic therapy for neovascular age-related macular degeneration (nAMD). Economic analysis. Adults undergoing serial intravitreal anti-VEGF injections in 1 eye for nAMD. Discounted cash flow modeling with scenario analysis was used to derive a present value for a 1-time alternative treatment to lifelong anti-VEGF treatment for nAMD. Multiple sensitivity analyses were performed on the basis of patient age at time of first injection and frequency interval of intravitreal injection. Present values of DCF and scenario analyses. Discounted cash flow analysis of intravitreal anti-VEGF treatment for nAMD resulted in a base-case valuation of $208 420.61, $219 093.31, and $17 379.41 for a 1-time alternative treatment to aflibercept, ranibizumab, and bevacizumab, respectively. This figure covaried significantly with anti-VEGF agent according to the patient age at first injection ($78 323.19-$292 449.87) and frequency of injections ($148 422.91-$388 096.81). In addition, for bevacizumab, variability was driven by the hypothetical degree of clinical superiority of 1-time therapy to repeated intravitreal injections due to reduction in adverse events ($17 379.41-$18 250.79) or reduction in direct or indirect costs associated with age-related macular degeneration ($17 379.41-$657 406.55). Anti-VEGF gene therapy approaches can create significantly different value propositions based on the agent modeled, patient age at first injection, frequency of injections, and clinical profile of the medication. Although the use of aflibercept or ranibizumab as a comparative cost metric is logical from a bioequivalence perspective, the disparity in medication costs should not be the primary value driver in applied models. Instead, bevacizumab should be the base case ($17 379.41), with additional value driven from an improvement in quality of life through clinical superiority. A reduction in direct and indirect costs can be used to approximate the value from maintained visual acuity, which is elaborated in the DCF analysis approach described in this article. This model can serve as a basis for assessing the price ceiling of myriad gene therapy approaches. Given the high present values for these therapeutics, innovative costing and reimbursement mechanisms should be further explored, with contingencies for sustained efficacy.


Is there fungal infestation in paediatric chronic otitis media - Mucosal disease?
To determine the prevalence of fungal infestation in paediatric chronic otitis media (COM)-mucosal disease and to study the various factors that might influence the said infestation. A cross-sectional study was done on the cited subject in a sample size of 66 paediatric patients [Age group: 1-18 years] suffering from active COM-mucosal disease. In all we had 75 ears from which swab samples were taken as some patients had bilateral disease. Clinical record was documented in each case. Three sample swabs were analysed for aerobic, anaerobic and fungal infection respectively from the discharging ear. Fungal infection was diagnosed by culture. The data was tabulated and statistically analysed for any correlation of fungal infestation with age, sex, background, duration of COM, previous antibiotic/steroid usage and intractable otorrhoea. We recorded a prevalence of 32% for fungal colonization of COM-mucosal disease in paediatric population i.e., 24 out of 75 ears. There was no association observed between fungal infestation and specific paediatric age group, sex, background or duration of the disease. However, a distinct statistical correlation was present between fungal infestation and previous antibiotic/steroid usage and intractable otorrhoea. Findings of this study lead us to conclude that all cases of paediatric COM-mucosal disease should be analysed for fungal colonization, especially those with intractable otorrhoea and there should be judicious use of antibiotics and steroid ear drops in COM-mucosal disease.


Effects of hypoxia on atrial muscarinic cholinergic receptors and cardiac parasympathetic responsiveness.
Chronic exposure of rats to hypoxia resulted in a lower resting heart rate and a supranormal increase in heart rate in response to parasympathetic blockade by atropine. The density of muscarinic cholinergic receptors labeled by the antagonist [3H]quinuclidinyl benzilate was elevated significantly in the atria of animals kept hypoxic for 2-4 weeks. Chronic hypoxia did not change the affinity of the receptor for [3H]quinuclidinyl benzilate, the weight of the atria, or the amount of protein per atrial pair. Thus, the decrease in resting heart rate may be explained by the increase in the density of atrial muscarinic cholinergic receptors.


Raman spectroscopy applied to identify metabolites in urine of physically active subjects.
Raman spectroscopy is a rapid and non-destructive technique suitable for biological fluids analysis. In this work, dispersive Raman spectroscopy has been employed as a rapid and nondestructive technique to detect the metabolites in urine of physically active subjects before and after vigorous 30min pedaling or running compared to sedentary subjects. For so, urine samples from 9 subjects were obtained before and immediately after physical activities and submitted to Raman spectroscopy (830nm excitation, 250mW laser power, 20s integration time) and compared to urine from 5 sedentary subjects. The Raman spectra of urine from sedentary showed peaks related to urea, creatinine, ketone bodies, phosphate and other nitrogenous compounds. These metabolic biomarkers presented peaks with different intensities in the urine of physically active individuals after exercises compared to before, measured by the intensity of selected peaks the Raman spectra, which means different concentrations after training. These peaks presented different intensity values for each subject before physical activity, also behaving differently compared to the post-training: some subjects presented increase while others decrease the intensity. Raman spectroscopy may allow the development of a rapid and non-destructive test for metabolic evaluation of the physical training in active and trained subjects using urine samples, allowing nutrition adjustment with the sport's performance.


A LC-MS/MS method for determination of clenbuterol enantiomers in animal tissues and its application to the enantioselective distribution in Bama mini-pigs.
To establish and validate a simple and reliable analytical method for separation and determination of clenbuterol enantiomers (R-(-)-clenbuterol & S-(+)-clenbuterol) in animal tissues, and apply it to the enantioselective distribution of clenbuterol in Bama mini-pigs. A LC-MS/MS analytical method was developed and validated in positive multiple reaction monitoring mode with electrospray ionization. After perchloric acid deproteinization, samples were pretreated only by one step liquid-liquid extraction using tert-butyl methyl ether under strong alkaline condition. Teicoplanin was used as chiral selector and 10 mM ammonium formate methanol solution was used as mobile phase. The optimized chromatographic separation conditions were completed in 8 min. Two chiral isomers in 11 edible tissues from Bama mini-pigs were investigated. R-(-)-clenbuterol and S-(+)-clenbuterol can be baseline separated and accurately analyzed with a linear range of 5-500 ng/g. Accuracies ranged from -11.9-13.0% for R-(-)-clenbuterol and -10.2-13.2% for S-(+)-clenbuterol, intra-day and inter-day precisions were between 0.7 and 6.1% for R-(-)-clenbuterol and 1.6-5.9% for S-(+)-clenbuterol. R/S ratios in edible tissues of pigs were all significantly lower than 1. The analytical method has good specificity and robustness in determination of R-(-)-clenbuterol and S-(+)-clenbuterol in animal tissues, and can be used as a routine analysis method for food safety and doping control. There is a significant difference in R/S ratio between pig feeding tissues and pharmaceutical preparations (racemate with R/S ratio of 1), which makes it possible to identify the source of clenbuterol in doping control and investigation.


Temporal variability of phytoplankton in tropical lakes.
Temporal variability of ecological systems continues to receive theoretical and empirical attention but remains inadequately documented at low latitudes. Results of my comparative investigation of photosynthetic rates of phytoplankton in 6 equatiorial African lakes and similar information from 20 South American, Asian and African lakes studied by others provide the data for an assessment of the range of seasonal variability (expressed as coefficients of variation, CV) among tropical lakes. Sampling intervals varied from 1 week to 3 months and usually spanned at least one year. Within Africa the coefficient of variation ranged from 15% to 61%, and among all the lakes the coefficient of variation ranged from 15% to 86%. The Spearman rank correlation coefficient of the CV's of photosynthesis versus latitude is 0.24 and is not significant at the 0.05 level.Coefficients of variation of photosynthetic rates of phytoplankton in a diverse set of 45 temperate and arctic lakes ranged from 29% to 155% and were significantly different from the set of 26 tropical lakes by the Mann-Whitney U test. When all 71 lakes are compared, the Spearman rank correlation coefficient of CV's of photosynthesis versus latitude is 0.71 and is significant at the 0.0005 level.Three temporal patterns were recognized among tropical lakes. Most tropical lakes exhibit pronounced seasonal fluctuations that usually correspond with variations in rainfall, river discharges or vertical mixing. A second pattern occurs in lakes with muted fluctuations (coefficient of variation less than 20%) in which diel changes often exceed month to month changes. A third pattern is distinguished by an abrupt change from one persistent algal assemblage (i.e., extant for at least 10 generations) and level of photosynthetic activity to another persistent condition.


Effects of chronic styrene inhalation on rat brain protein metabolism.
Adult male rats were exposed to 7.9 mumol/1 (300 ppm) of styrene for 2--11 weeks 6 h daily excluding Saturdays and Sundays. The exposures caused a marked styrene accumulation in brain and perinephric fat, and the accumulation tended to increase upto the 4th week. The body styrene content decreased thereafter gradually towards the end of the experiment to reach half of the styrene content of the 4th week. Serum creatine kinase activity increased at the initial stage of the exposures while serum non-specific cholinesterase was below the control range at the same time. Earliest biochemical changes were detected at the 9th week of exposure, and they included increased activity of lysosomal acid proteinase. Increased enzyme activity prevailed to the end of the exposures. Simultaneous minor alterions could be detected in spinal cord axonal protein pattern whereas water-soluble protein composition in cerebellum did not change. Biochemical alterations in brain were not accompanied by significant changes in serum enzyme activities. It is concluded that marked metabolic adaptation to inhaled styrene takes place. Serum enzyme determinations may prove valuable in the adaptation period whereas they may not reflect beginning chronically neurotoxic effects.


Biomechanical properties and histological structure of sinus of Valsalva aneurysms in relation to age and region.
Information on the biomechanical properties of aortic root aneurysms that would facilitate our understanding of their rupture modes is currently unavailable. In this study, whole-thickness wall specimens from aortic root aneurysms were studied in vitro so as to compare the biomechanical properties with gross histomorphology and composition, in relation to age, region, and direction. The stress-strain relationship was determined under uniaxial loading conditions and characterized by the Fung-type material model in terms of optimized material constants; failure properties were recorded. The connective tissue contents of the basic scleroproteins were also determined through computerized histology. Aging had a deleterious influence on the tensile strength of the aneurysmal sinus tissue, causing also stiffening and reduced extensibility that was consistent with the deficient elastin and collagen contents. Direction-dependent differences were demonstrated in the noncoronary sinus, with the circumferential being stiffer and stronger than the longitudinal direction, justified by the preferred collagen reinforcement along that direction there. In the left and right coronary sinus, the material constants and failure properties were essentially the same in the two directions, justified by the arbitrary orientation of medial (collagen and elastin fibers, and cellular) components relative to the circumferential-longitudinal directions. The material characterization results afforded, and the regional and age-related differences in the strength of the sinus wall, i.e. in its capacity to withstand hemodynamic stresses, are hoped to provide novel insight into the pathophysiological mechanisms responsible for the highest incidence of ruptured aortic root aneurysms in the right coronary and noncoronary sinus.


Pyruvate carboxylase deficiency and lactic acidosis in a retarded child without Leigh's disease.
A child with lactic acidosis, severe mental and developmental retardation, and proximal renal tubular acidosis is presented. Biopsy and autopsy studies show severe hepatic, renal cortical, and cerebral deficiencies in pyruvate carboxylase (EC 184.108.40.206) activity. The patient had 1.81 +/- 0.20 units/g fresh weight at biopsy and 0.75 +/- 0.07 units/g fresh weight hepatic pyruvate carboxylase activity at autopsy compared with 10.9, 11.3, and 9.5 units/g fresh weight in two autopsy and one biopsy controls, respectively. The patient's renal cortical pyruvate carboxylase activity at autopsy was 0.008 +/- 0.004 units/g fresh weight compared with 5.05 units/g in the autopsy control. The patient had no detectable (less than 0.018 units/g fresh weight) cerebral pyruvate carboxylase activity at autopsy compared with 0.44, 0.53, and 0.695 units/g in the autopsy cerebrum of one human and two rhesus monkeys, respectively. Pyruvate dehydrogenase complex, phosphoenolpyruvate carboxykinase (PEPCK, EC 188.8.131.52), and fructose-1,6-bisphosphatase (EC 126.96.36.199) activities were in the normal range. The patient's urine pH was above 7.9 when the total serum CO2 was greater than 7.8 mM. However, the patient was able to acidify the urine to pH 5.1 when the total serum CO2 was 1.6 mM. The neuropathologic examination of the brain at autopsy revealed no sign of Leigh's disease, although developmental and degenerative lesions were observed. This is the first reported patient with a primary deficiency in hepatic, renal, and cerebral pyruvate carboxylase deficiency in whom the neuropathologic lesions, distinct from those of Leigh's disease, and proximal renal tubular acidosis have both been documented.


An immunological approach to vaccines against African swine fever virus.
Until recently there were no published reports of any immunological mechanism which could curtail the replication of African swine fever virus (ASFV). We have now described three such mechanisms--complement dependent lysis, antibody dependent cellular cytotoxicity and cytotoxic T lymphocytes. This paper discusses the likely role which each might play during ASFV infection and indicates where this research might help with a disease where no effective vaccine is available.


Clinical Value of Serum Levels of 11-Oxygenated Metabolites of Testosterone in Women With Polycystic Ovary Syndrome.
Recent data suggested that 11-oxygenated androgens may be the preponderant circulating androgens in women with PCOS. However, the pathophysiological significance of these hormones remains unclear. The aim of this study was to evaluate the relationships between serum 11-OH testosterone (11-OHT) and 11-keto testosterone (11-KetoT) and clinical and biochemical hyperandrogenism, as well as the metabolic parameters, in women with PCOS. The main classic and 11-oxygenated androgens were measured by LC-MS/MS and direct equilibrium dialysis in 123 women with PCOS, diagnosed according to the Rotterdam criteria, and 38 healthy controls. Insulin sensitivity was assessed by hyperinsulinemic euglycemic clamp. Serum 11-oxygenated androgens were higher in women with PCOS than in controls. Elevated levels of 11-OHT and 11-KetoT were found in 28.5% and 30.1% of PCOS women, respectively, whereas free testosterone (FT) was increased in 61.0% of them. Serum 11-oxygenated androgens showed a limited performance in recognizing women with classically defined hyperandrogenism. Unlike FT, 11-oxygenated androgens did not show significant relationships with anthropometric and metabolic parameters, except for a direct association with insulin sensitivity. In multivariable analysis, 11-OHT and 11-KetoT, directly, and FT, inversely, remained significant independent predictors of insulin sensitivity. Serum levels of 11-oxygenated androgens are higher in women with PCOS than in controls. However, these hormones show a poor performance in recognizing women with hyperandrogenism, as currently defined. The relationships of these androgens with insulin sensitivity strongly differ from that of FT, suggesting a different role of classic and 11-oxygenated androgens in the pathophysiology of PCOS.


Valsalva retinopathy induced by handstand: a case report.
Valsalva retinopathy is known to occur as a sudden preretinal or sub-internal limiting membrane hemorrhage induced by a rapid rise in venous pressure following increased intrathoracic or intraabdominal pressure. Here we report a case of Valsalva retinopathy that was probably induced by straining that occurred due to following a handstand. A 15-year-old boy became aware of decreased visual acuity in his left eye immediately after doing a handstand for approximately 10 s during physical education class, and subsequently visited a local clinic on the same day. Upon examination, a vitreous hemorrhage (VH) in the posterior pole of the fundus was found in his left eye, and he was subsequently referred to our department 7 days later. Upon examination, the VH around the optic nerve head of the left eye appeared to be resolved, and an oval-shaped sub-internal limiting membrane (sub-ILM) hemorrhage was found in the superonasal side of the optic nerve head. No abnormalities were observed in the macular area. Four months later, the sub-ILM hemorrhage was found to have spontaneously resolved. Subsequent fluorescein angiography examinations revealed no abnormal findings at the lesion site. In this patient, we hypothesize that the Valsalva retinopathy was induced by straining that occurred due to a handstand, and that the resultant sub-ILM hemorrhage progressed to VH.


Serine 68 phospholemman phosphorylation during forskolin-induced swine carotid artery relaxation.
Phospholemman (PLM) is an abundant phosphoprotein in the plasma membrane of cardiac, skeletal and smooth muscle. It is a member of the FXYD family of proteins that bind to and regulate the Na,K-ATPase. Protein kinase A (PKA) is known to phosphorylate PLM on serine 68 (S68), although the functional effect of S68 PLM phosphorylation is unclear. We therefore evaluated S68 PLM phosphorylation in swine carotid arteries. Two anti-PLM antibodies, one to S68 phosphorylated PLM and one to unphosphorylated PLM, were made to PLM peptides in rabbits and tested with purified PLM and PKA-treated PLM. Swine carotid arteries were mounted isometrically, contracted, relaxed with forskolin and then homogenized. Proteins were separated on SDS gels and the intensity of immunoreactivity to the two PLM antibodies determined on immunoblots. The antipeptide antibody 'C2' primarily reacted with unphosphorylated PLM, and the antipeptide antibody 'CP68' detected S68 PLM phosphorylation. Histamine stimulation of intact swine carotid artery induced a contraction, increased the CP68 PLM antibody signal and reduced the C2 PLM antibody signal. High extracellular [K(+)] depolarization induced a contraction without altering the C2 or CP68 PLM signal. Forskolin-induced relaxation of histamine or extracellular [K(+)] contracted arteries correlated with an increased CP68 signal. Nitroglycerin-induced relaxation was not associated with changes in the C2 or CP68 PLM signal. These data suggest that a contractile agonist increased S68 PLM phosphorylation. Agents that increase [cAMP], but not agents that increase [cGMP], increased S68 PLM phosphorylation. S68 PLM phosphorylation may be involved in cAMP-dependent regulation of smooth muscle force.


Hernia width explains differences in outcomes between primary and incisional hernias: a prospective cohort study of 9159 patients.
Data on primary (PH) and incisional hernias (IH) are often pooled, even though several studies have illustrated that these are different entities with worse outcomes for IHs. The aim of this study is to validate previous research comparing PHs and IHs and to examine whether hernia width is an important contributor to the differences between these hernia types. A registry-based, prospective cohort study was performed, utilizing the French Hernia Club database. All patients undergoing PH or IH repair between September 8th 2011 and May 22nd 2019 were included. Baseline, hernia and surgical characteristics, and postoperative outcomes were collected. Outcomes were analyzed per width category (≤ 2 cm, 3-4 cm, 5-10 cm and > 10 cm). A total of 9159 patients were included, of whom 4965 (54%) had PH and 4194 (46%) had IH. PHs and IHs differed significantly in 12/15 baseline characteristics, 9/10 hernia and surgical characteristics, and all outcomes. Overall, complications and re-interventions were more common in patients with IH. After correcting for width, the differences between PH and IH were no longer significant, except for medical complications, which were more common after IH repair compared to PH. After correcting for hernia width, most outcomes do not significantly differ between PH and IH, indicating that not hernia type, but hernia width is an important factor contributing to the differences between PH and IH.


MRI-guided trephine biopsy and fine-needle aspiration in the diagnosis of bone lesions in low-field (0.23 T) MRI system using optical instrument tracking.
The purpose of this study was to evaluate the feasibility of MRI-guided bone biopsy with optical instrument tracking and evaluate advantage of combined fine-needle aspiration (FNA) with trephine biopsy. Twenty trephine bone biopsies and 13 FNAs were performed under MRI and CT guidance in 14 patients. Informed consent was obtained from all patients. The evaluation of diagnostic accuracy was achieved by comparing the histopathological and cytological diagnosis with current or final diagnosis made during 6-month clinical follow-up. A 0.23-T open MRI scanner with interventional tools (Outlook Proview, Marconi Medical Systems, Cleveland, Ohio) was used. A surface coil was used. For trephine biopsy MRI-compatible bone biopsy set (Daum medical, Schwerin, Germany) was used. The FNA was performed with MRI compatible 20-G needle (Cook, Bloomington, Ind.). The diagnostic accuracy of MRI-guided trephine biopsy was 95%. The FNA sample diagnosis concurred with the histological in 54%. Our results show that MRI guidance in bone biopsies is accurate and safe. It is comparable to CT-guided or open biopsy. The role of combined FNA with bone biopsies remains controversial.


Acute respiratory distress syndrome due to SARS-CoV-2 and Influenza A co-infection in an Italian patient: Mini-review of the literature.
A case of acute respiratory distress syndrome due to SARS-CoV-2 and Influenza A co-infection and a mini-review of the literature is reported. Even in COVID-19 epidemics, the early identification of concurrent respiratory pathogens is important to improve etiological diagnosis, preventive measures and patients' clinical management and outcome.


The development of vision in cats after extended periods of dark-rearing.
The time course of development of visual acuity for square wave gratings was measured behaviourally in a number of cats that were reared in total darkness until they were either 4 (5 cats) or 6 (1 cat) months of age. Less extensive measurements were also made on animals reared in a similar manner until they were either 1 1/2 or 10 months old. Initially, all the animals appeared to be blind, but signs of vision became evident after periods of time in an illuminated environment that ranged from a few days, in the case of animals dark-reared for only 1 1/2 to 4 months, to 1 to 2 months for those animals that were deprived for 6 months or more. Thereafter, visual acuity as measured on a jumping stand progressively improved, reaching, in the case of animals deprived for 4 months, values that were comparable to those of normal animals (6.9 cycles/deg) after 4 months of exposure to light. The animal deprived for 6 months remained apparently blind for a month and eventually attained an acuity (5.7 cycles/deg) that was somewhat less than that of normal animals. The fact that such high acuities can be achieved after periods of binocular deprivation that extend throughout the classically defined "critical period" suggest that the effect of dark-rearing is somehow to impede the natural decline with age in the degree to which cortical neurones are susceptible to environmental modification.


Polychrome labeling of bone with seven different fluorochromes: enhancing fluorochrome discrimination by spectral image analysis.
Bone formation and remodeling in vivo can be assessed by polychrome labeling using calcium-binding fluorescent dyes. The number of fluorochromes, however, limits this technique due to the fact that with increasing number, fluorescent spectra inevitably overlap, which makes discrimination more difficult. In order to enhance discrimination, we performed spectral image analysis. Non-critical size defects of the femur of male Wistar rats served as a model for bone formation. Eight different fluorochromes (calcein blue, xylenol orange, calcein, alizarine complexone, doxycycline, rolitetracycline, hematoporphyrin, and BAPTA) were administered sequentially subcutaneously every third day starting at day 4 after surgery. Following, bone specimen were embedded in methylmethacrylate and analyzed by spectral image acquisition using a Sagnac type interferometer (ASI, Israel). Seven of the eight applied fluorochromes could be resolved using spectral image examination. With BAPTA, we present a new fluorochrome suitable for bone labeling. Due to the superior sensitivity of the spectral image acquisition, the thickness of the bone sections could be reduced so that 5 mum thick sections could be analyzed. Spectral decomposition and subsequent linear unmixing allows depiction of each individual fluorochrome without interference of any other, enabling a reliable and superior morphometric analysis of labeled regions.


Evaluation of Three Sensor Types for Particle Motion Measurement.
All fish sense acoustic particle motion; some species also sense pressure. Concern over the effects of anthropogenic sounds is increasing the need to monitor acoustic particle motion. Particle motion can be measured directly using vector sensors or calculated from pressure gradients. This article compares three devices that measure particle motion: a three-axis accelerometer, a three-axis velocity sensor, and two 4-element hydrophone arrays. A series of sounds (constant-wave tones, white noise, and Ricker wavelets) were played from a fixed-position projector. The particle motion of sounds from imploding light bulbs was also measured.


Outcome-dependent sampling in cluster-correlated data settings with application to hospital profiling.
Hospital readmission is a key marker of quality of healthcare and an important policy measure, used by the Centers for Medicare and Medicaid Services to determine, in part, reimbursement rates. Currently, analyses of readmissions are based on a logistic-normal generalized linear mixed model that permits estimation of hospital-specific measures while adjusting for case mix differences. Recent moves to identify and address healthcare disparities call for expanding case mix adjustment to include measures of socio-economic status while minimizing additional burden to hospitals associated with collecting data on such measures. Towards resolving this dilemma, we propose that detailed socio-economic data be collected on a subsample of patients via an outcome-dependent sampling scheme, specifically the cluster-stratified case-control design. Estimation and inference, for both the fixed and the random-effects components, are performed via pseudo-maximum-likelihood wherein inverse probability weights are incorporated in the usual integrated likelihood to account for the design. In comprehensive simulations, cluster-stratified case-control sampling proves to be an efficient design whenever interest lies in fixed or random effects of a generalized linear mixed model and covariates are unobserved or expensive to collect. The methods are motivated by and illustrated with an analysis of N = 889661 Medicare beneficiaries hospitalized between 2011 and 2013 with congestive heart failure at one of K = 3116 hospitals. Results highlight that the framework proposed provides a means of mitigating disparities in terms of which hospitals are indicated as being poor performers, relative to a naive analysis that fails to adjust for missing case mix variables.


The Facial Adipose System: Its Role in Facial Aging and Approaches to Volume Restoration.
Volume loss in facial adipose tissue plays a critical role in the aesthetics of facial aging. Furthermore, the facial adipose system is a complex network of distinct compartments, and a detailed understanding of these compartments is essential for optimal facial volume restoration. To review the facial adipose system, age-related changes, and the role of volume restoration products for facial rejuvenation. Publications including deceased donors' dissection studies and more recent studies using computed tomography were reviewed to provide an up-to-date understanding of the facial adipose system anatomy and age-related changes. Current volume restoration treatment options including hyaluronic acid, calcium hydroxylapatite, and poly-L-lactic acid are discussed. Facial aging is associated with volume loss in superficial and deep adipose compartments, including those of the forehead, cheek, lip, chin, and jowl areas. Volume restoration products can be used to address the age-related changes of the facial adipose compartments. Understanding the complex network of facial adipose compartments and their age-related changes allows for the optimal use of injectable volume restoration products for facial rejuvenation that can be customized to the anatomical needs of each patient.


Serotonergic mediation of cocaine seizures in mice.
We used genetically heterogeneous HS mice to investigate the effects of drugs that alter brain concentrations of serotonin on cocaine-induced convulsions and lethality. The racemer of fenfluramine, which increases synaptic serotonin, was coadministered with a dose (60 mg/kg, intraperitoneally) of cocaine that does not produce status epilepticus or death. This drug combination significantly increased the occurrence and decreased the time of onset of status epilepticus, but did not affect lethality. Likewise, 2.5 mg/kg of the D-isomer, of fenfluramine increased the occurrence of status epilepticus. Neither isomer effected lethality. When 2.5 mg/kg cinanserin, a drug that antagonizes postsynaptic serotonergic receptors, was coadministered with a higher (95 mg/kg) dose of cocaine, the time of onset of status epilepticus was significantly increased, whereas lethality was reduced. The results are discussed in light of the action of cocaine upon serotonin neurons and the relationship between seizurogenic activity and cocaine-induced lethality.


Effect of erythropoietin as an adjunct to primary percutaneous coronary intervention: a randomised controlled clinical trial.
The acute administration of high-dose erythropoietin (EPO) on reperfusing ischaemic myocardium has been reported to halve myocardial infarct (MI) size in preclinical studies, but its effect in ST elevation myocardial infarction patients undergoing primary percutaneous coronary intervention (PPCI) remains unknown. We investigated whether high-dose EPO administered as an adjunct to PPCI reduces MI size. Double-blinded, randomised, placebo-controlled. Single tertiary cardiac centre. Fifty-one ST elevation myocardial infarction patients undergoing PPCI. Patients were randomly assigned to receive either a single intravenous bolus of EPO (50,000 IU) prior to PPCI with a further bolus given 24 h later (n=26) or placebo (n=25). MI size measured by 24 h area under the curve troponin T and cardiac magnetic resonance imaging performed on day 2 and at 4 months. EPO treatment failed to reduce MI size (troponin T area under the curve: 114.6±78 μg/ml EPO vs 100.8±68 μg/ml placebo; infarct mass by cardiac magnetic resonance: 33±16 g EPO vs 25±16 g placebo; both p>0.05). Unexpectedly, EPO treatment doubled the incidence of microvascular obstruction (82% EPO vs 47% placebo; p=0.02) and significantly increased indexed left ventricular (LV) end-diastolic volumes (84±10 ml/m(2) EPO vs 73±13 ml/m(2) placebo; p=0.003), indexed LV end-systolic volumes (41±9 ml/m(2) EPO vs 35±11 ml/m(2) placebo; p=0.035) and indexed myocardial mass (89±16 g/m(2) EPO vs 79±11 g/m(2) placebo; p=0.03). At 4 months, there were no significant differences between groups. High-dose EPO administered as an adjunct to PPCI failed to reduce MI size. In fact, EPO treatment was associated with an increased incidence of microvascular obstruction, LV dilatation and increased LV mass. Clinical Trial Registration Information http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=4058 Unique Identifier=Study ID 4058.


Surgical Outcomes and Postoperative Prognosis Beyond 10 Years for Double-Chambered Right Ventricle.
Double-chambered right ventricle (DCRV) is a rare condition. Stenosis of DCRV is progressive, and early surgical intervention is recommended for patients whose symptoms and/or pressure overload of right ventricular (RV) inflow are progressive. However, there are few data regarding the postoperative course of DCRV, and the surgical indications for asymptomatic patients remain to be determined. We retrospectively investigated 38 consecutive patients who were diagnosed with DCRV and underwent surgical intervention from 1981 to 2009. Moreover, we identified 29 patients in whom long-term follow-up transthoracic echocardiographic data were available and investigated the postoperative recurrence of DCRV by evaluating the systolic pressure of RV inflow before, immediately, and in the long term after surgical intervention. The mean follow-up period was 11.0 ± 8.8 years. There were no deaths and no surgical reinterventions during the long-term follow-up period. Among 29 patients with long-term follow-up echocardiographic data, there was no recurrence of DCRV. In these patients, the systolic pressure of RV inflow by echocardiography before, immediately, and long-term after surgical intervention was 80 ± 26, 30 ± 11, and 25 ± 6 mm Hg, respectively. In conclusion, the surgical outcomes and postoperative prognosis beyond 10 years of DCRV are favorable, and neither recurrence of DCRV nor fatal arrhythmias develop during the long-term follow-up period.


Fitness is Recovered with the Decline of Dimethachlon Resistance in Laboratory-induced Mutants of Sclerotinia sclerotiorum after Long-term Cold Storage.
After four years of cold storage, dimethachlon resistance of two laboratory-induced resistant Sclerotinia sclerotiorum isolates SCG7 and LA50 declined by 99.5% and 98.9%, respectively, and cross resistance to iprodione and procymidone also declined dramatically. Along with the decline of fungicide resistance, osmotic sensitivity to sodium chloride and glucose decreased tremendously; mycelial growth rate, sclerotia number and weight per potato dextrose agar (PDA) plate increased on average by 118.6%, 85. 5% and 64.5%, respectively; and virulence to detached leaves of oilseed rape increased by 72.7% on average. Significant negative correlations were detected between dimethachlon resistance levels and mycelial growth rate on PDA (r = -0.980, P = 0.021), and between resistance levels and lesion diameters on detached leaves of oilseed rape plants (r = -0.997, P = 0.002). These results have profound implications for assessing the potential risk for resistance development to dicarboximide fungicides in S. sclerotiorum.


The hemoglobins of the bullfrog, Rana catesbeiana. Deoxygenation-linked association of tetrameric components B and C to form the trimer BC2: sedimentation analysis and oxygen equilibria.
Hemolysates from the adult bullfrog, Rana catesbeiana, show an unusually high degree of cooperativity of oxygen binding with Hill coefficients greater than 4. The principal components of the tetrameric hemoglobin, B and C, do not show this high cooperativity when isolated, but it reappears when the components are mixed. Sedimentation velocity measurements show that the unusual behavior results from the mixed association of components B and C to form complexes larger than tetramers. Computer simulation of the sedimentation behavior of mixtures of deoxygenated B and C components shows that the gradient profiles can be satisfactorily described in terms of an equilibrium between the B and C tetramers and a BC2 trimer. The simplest model consistent with the results is the mixed association: B + C<-->BC and BC + C<-->BC2, with the second binding constant being higher than the first, indicating significant cooperativity. The extent of association is highest at low pH and low temperature. The dissociation of the B.C complex with low oxygen affinity to higher affinity B and C molecules during oxygenation results in greatly increased cooperativity of oxygen binding with higher Hill coefficients than possessed by either component alone in equilibria measured between 5 and 25 degrees C and between pH 6 and 8.


Clinical Utility of a Plasma Protein Classifier for Indeterminate Lung Nodules.
Evaluation of indeterminate pulmonary nodules is a complex challenge. Most are benign but frequently undergo invasive and costly procedures to rule out malignancy. A plasma protein classifier was developed that identifies likely benign nodules that can be triaged to CT surveillance to avoid unnecessary invasive procedures. The clinical utility of this classifier was assessed in a prospective-retrospective analysis of a study enrolling 475 patients with nodules 8-30 mm in diameter who had an invasive procedure to confirm diagnosis at 12 sites. Using this classifier, 32.0 % (CI 19.5-46.7) of surgeries and 31.8 % (CI 20.9-44.4) of invasive procedures (biopsy and/or surgery) on benign nodules could have been avoided. Patients with malignancy triaged to CT surveillance by the classifier would have been 24.0 % (CI 19.2-29.4). This rate is similar to that described in clinical practices (24.5 % CI 16.2-34.4). This study demonstrates the clinical utility of a non-invasive blood test for pulmonary nodules.


Characterization, anti-oxidative and anti-inflammatory effects of Costa Rican noni juice (Morinda citrifolia L.).
Noni fruit (Morinda citrifolia L.) juice has been used for more than 2000 years in Polynesia as a traditional folk medicine. The aim of the present study was to finely characterize noni juice from Costa Rica and to evaluate its anti-oxidative and anti-inflammatory activities. A microfiltrated noni juice was prepared with Costarican nonis. HPLC-DAD and Electro Spray Ionization Mass Spectrometric detection (HPLC-ESI-MS) were used to identify phenolic compounds and iridoids. The anti-oxidative activity of noni juice was measured in vitro by both Oxygen Radical Absorbance Capacity (ORAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging methods. The anti-inflammatory effects of noni juice were investigated in vitro by: measuring its effect on nitric oxide and prostaglandin E2 production by activated macrophages, evaluating its inhibitory activities on cyclooxygenase (COX)-1 and -2 and in vivo on a carrageenan-induced paw oedema model in rats. Several polyphenols belonging to the coumarin, flavonoid and phenolic acid groups, and two iridoids were identified. Noni juice demonstrated a mean range free radical scavenging capacity. Furthermore, it also reduced carrageenan-induced paw oedema, directly inhibited cyclooxygenase COX-1 and COX-2 activities and inhibited the production of nitric oxide (NO) and prostaglandins E(2) (PGE(2)) in activated J774 cells, in a dose dependent manner. This study showed that noni's biological effects include: (1) anti-oxidant properties probably associated with phenolic compounds, iridoids and ascorbic acid and (2) anti-inflammatory action through NO and PGE(2) pathways that might also be strengthened by anti-oxidant effects.


[Rheumatism operations in a state of flux-"Foot"].
Surgical management of rheumatic feet has dramatically changed over the last decades influenced by the development of new pharmacological drugs and tissue-preserving surgical procedures. It has switched from joint resection to joint-sparing procedures as the method of choice. Nevertheless, the surgical interventions commonly used for non-rheumatic patients cannot be applied to rheumatic patients without reflection: in addition to the basic treatment, comorbidities, degree of mobilization of the patient, orthopedic shoe engineering and orthotic treatment play a major role. Due to the decreasing incidence of the classical rheumatic foot, it has become even more important for physicians, physiotherapists and ergotherapists to recognize the development of such a disease as early as possible and immediately start the appropriate treatment.


Retained Surgical Items: Lessons from Australian Case Law of Items Unintentionally Left Behind in Patients after Surgery.
The retention of items within a patient after surgery is considered to be a serious issue within the health care community. Termed a "sentinel event", a retained surgical item (RSI) is one of eight reportable adverse events deemed to have the potential to seriously undermine the health care system in the eyes of the public. Yet despite the gravity of these events, there has been little opportunity for the courts to examine the liability issues surrounding RSIs. This article reviews the limited case law in this area and analyses the key legal issues which arise in claims for redress, including civil, criminal and disciplinary liability, involving those who have suffered harm from RSIs.


Cardiovascular activities of the bradykinin system.
All the components of the kallikrein-kinin system are located in the cardiac muscle and its deficiency may lead to cardiac dysfunction. In recent years, numerous observations obtained from clinical and experimental models of diabetes, hypertension, cardiac failure, ischemia, myocardial infarction, and left ventricular hypertrophy have suggested that the reduced activity of the local kallikrein-kinin system may be instrumental for the induction of cardiovascular-related diseases. The cardioprotective property of the angiotensin-converting enzyme inhibitors is primarily mediated via a kinin-releasing pathway, which may cause regression of the left ventricular hypertrophy in hypertensive situations. The ability of kallikrein gene delivery to produce a wide spectrum of beneficial effects makes it a promising candidate in treating hypertension and cardiovascular and renal diseases. In addition, stable kinin agonists may also be available in the future as therapeutic agents for cardiovascular and renal disorders. However, there are also possibilities of adverse effects that may be caused by these compounds.


Transcriptomic comparison of the self-pollinated and cross-pollinated flowers of Erigeron breviscapus to analyze candidate self-incompatibility-associated genes.
Self-incompatibility (SI) is a widespread and important mating system that promotes outcrossing in plants. Erigeron breviscapus, a medicinal herb used widely in traditional Chinese medicine, is a self-incompatible species of Asteraceae. However, the genetic characteristics of SI responses in E. breviscapus remain largely unknown. To understand the possible mechanisms of E. breviscapus in response to SI, we performed a comparative transcriptomic analysis with capitulum of E. breviscapus after self- and cross-pollination, which may provide valuable information for analyzing the candidate SI-associated genes of E. breviscapus. Using a high-throughput next-generation sequencing (Illumina) approach, the transcriptionexpression profiling of the different genes of E. breviscapus were obtained, some results were verified by quantitative real time PCR (qRT-PCR). After assembly, 63,485 gene models were obtained (average gene size 882 bp; N50 = 1485 bp), among which 38,540 unigenes (60.70% of total gene models) were annotated by comparisons with four public databases (Nr, Swiss-Prot, KEGG and COG): 38,338 unigenes (60.38% of total gene models) showed high homology with sequences in the Nr database. Differentially expressed genes were identified among the three cDNA libraries (non-, self- and cross-pollinated capitulum of E. breviscapus), and approximately 230 genes might be associated with SI responses. Several these genes were upregulated in self-pollinated capitulum but downregulated in cross-pollinated capitulum, such as SRLK (SRK-like) and its downstream signal factor, MLPK. qRT-PCR confirmed that the expression patterns of EbSRLK1 and EbSRLK3 genes were not closely related to SI of E. breviscapus. This work represents the first large-scale analysis of gene expression in the self-pollinated and cross-pollinated flowers of E. breviscapus. A larger number of notable genes potentially involved in SI responses showed differential expression, including genes playing crucial roles in cell-cell communication, signal transduction and the pollination process. We thus hypothesized that those genes showing differential expression and encoding critical regulators of SI responses, such as MLPK, ARC1, CaM, Exo70A1, MAP, SF21 and Nod, might affect SI responses in E. breviscapus. Taken together, our study provides a pool of SI-related genes in E. breviscapus and offers a valuable resource for elucidating the mechanisms of SI in Asteraceae.


Morphological adaptation of shape to flow: Microcurrents around lotic macroinvertebrates with known Reynolds numbers at quasi-natural flow conditions.
Using Laser Doppler Anemometry we measured current velocities in the median plane around dead lotic macroinvertebrates in a flume which reproduced natural near bottom hydraulics. We investigated specimens of the gastropods Ancylus, Acroloxus, and Potamopyrgus, the amphipod Gammarus, and the larval caddisflies Anabolia, Micrasema, and Silo of various size, various alignment to the flow or which were otherwise manipulated in order to clarify certain questions of adaptation of shape or case building style to flow, or the effects of flow on field distribution patterns. The steepest velocity gradients close to the animals were found near areas of their bodies protruding furthest into the flow. In such regions the rates of potential diffusive exchange processes, the potential corrasion (abrasion through suspended solids), and, for larger specimens, the lift forces (directed towards the water surface) must be highest. Posterior of these areas growing boundary layers formed above those species whose upper contour was approximately parallel to the upstream-downstream direction of the flow. All specimens removed momentum from the flow and thus experience a drag force (directed downstream). From the complete data set we derived the following general conclusions about the physical effects of potential morphological adaptations, taking into consideration diffusion through boundary layers, corrasion, lift forces, friction and pressure drag forces: The physical significance of these five factors generally depends on the Reynolds number of an animal and is largely affected by flow separation, which was significantly related to the ratio of body length to height and the slope of the posterior contour. A simultaneous effective morphological adaptation to all five factors is physically impossible and, in addition, would have to change from life at low (e.g. a young, small specimen of a species) to life at high (e.g. a fully grown specimen of the same species) Reynolds number.


Effect of inhibition of glucose and fat metabolism on galanin-R1 receptor mRNA levels in the rat hypothalamic paraventricular and supraoptic nuclei.
Using in situ hybridization histochemistry we have studied the effect of glucose and fat deprivation on galanin-R1 receptor (GAL-R1-R) mRNA levels in the rat paraventricular (PVN) and supraoptic (SON) nuclei after single and repeated i.p. administration of a glucose antimetabolite 2-deoxy-D-glucose (DG), as well as of a fatty acid antimetabolite, sodium mercaptoacetate (MA), treatments known to increase food intake. Both DG and MA injections caused an increase in levels of GAL-R1 mRNA transcripts in the PVN and SON. These results indicate that glucose and fat deprivation increase the sensitivity of PVN and SON neurons to galanin, and that regulation of receptor levels may be an important mechanism in galaninergic signalling.


Staphylococcal enterotoxin A modulates intracellular Ca2+ signal pathway in human intestinal epithelial cells.
We demonstrate here that staphylococcal enterotoxin A (SEA) induces an increase in intracellular calcium ([Ca2+]i) in human intestinal epithelial cells and the [Ca2+]i is released from intracellular stores. SEA-induced increase of [Ca2+]i was clearly inhibited by treatment with a nitric oxide synthase (NOS) inhibitors, N(G)-monomethyl-L-arginine and guanidine. Intestinal epithelial cells express endothelial NOS in resting cell condition, and express inducible NOS after stimulating with tumor necrosis factor (TNF)-alpha. TNF-alpha-pretreated cells showed a significant increase in [Ca2+]i that was also inhibited by the NOS inhibitor. These results suggest that SEA modulated [Ca2+]i signal is dependent on NOS expression in human intestinal epithelial cells.


Out-of-Hospital emergency airway management practices: A nationwide observational study from Aotearoa New Zealand.
Airway management is crucial for emergency care in critically ill patients outside the hospital setting. An Airway Registry is useful in providing essential information for quality improvement purposes. Therefore, this study aimed to develop an out-of-hospital airway registry and describe airway management practices in Aotearoa New Zealand (AoNZ). Data from the Aotearoa New Zealand Paramedic Care Collection (ANZPaCC) database were used in a retrospective cohort study covering July 2020 to June 2021. All patients receiving airway interventions were included. An airway intervention was defined as one or more of the following: non-drug assisted endotracheal intubation (NDA-ETI), drug-assisted endotracheal intubation (DA-ETI; where a combination of paralytic agent and sedative were used to aid in intubation), laryngeal mask airway (LMA), oropharyngeal airway (OPA), nasopharyngeal airway (NPA), surgical airway (cricothyroidotomy), suction, jaw thrust. Descriptive statistics were analysed using Chi-Square and logistic regression modelling investigated the relationship between advanced airway success and patient characteristics. The study included 4,529 patients who underwent 7,779 airway interventions. Basic airway interventions were used most frequently: OPA (45.1%), NPA (29.3%), LMA (28.9%), suction (19.9%) and jaw thrust (17.6%). Advanced airway interventions were used less frequently: NDA-ETI (19.8%), DA-ETI (8.7%), and surgical airways (0.2%). The success rate for ETI (including both NDA-ETI and DA-ETI) was 89.4%, with NDA-ETI success at 85.8% and DA-ETI success at 97.7%. ETI first-pass success rates were significantly lower for males (aOR 0.65, 95%CI 0.48-0.87, p < 0.001) and higher for non-cardiac arrest injury patients (aOR 2.94, 95%CI 1.43-6.00, p < 0.001). In this cohort receiving airway interventions the 1-day mortality rate was 41.1%, demonstrating that a high proportion of these patients were severely clinically compromised. Out-of-hospital airway management practices and success rates in AoNZ are comparable to those elsewhere. This research has determined the variables to be used as the AoNZ Paramedic Airway Registry ongoing and has demonstrated baseline outcomes in airway management for ongoing quality improvement using this registry.


Affordable housing through the low-income housing tax credit program and intimate partner violence-related homicide.
The most severe outcome of intimate partner violence (IPV) is IPV-related homicide. Access to affordable housing may both facilitate exit from abusive relationships and reduce financial stress in intimate relationships, potentially preventing IPV-related homicide. We examined the association of the availability of rental housing through the Low-Income Housing Tax Credit (LIHTC) program, a federal program providing tax incentives to support the development of affordable housing, with IPV-related homicide and assessed whether this association differed by eviction rates at the state-level. We used 2005-2016 National Violent Death Reporting System, LIHTC Property, and Eviction Lab data for 13 states and compared the rate of IPV-related homicide in state-years with ≥30 to state-years with <30 LIHTC units per 100,000 population, overall and stratified by eviction rates. We conducted analyses in fall 2020. Adjusting for potential state-level confounders, the rate of IPV-related homicide in state-years with ≥30 LIHTC units per 100,000 population was lower than in state-years with <30 LIHTC units per 100,000 population (RR = 0.89, 95% CI 0.81, 0.98). The reduction in the rate of IPV-related homicide was slightly larger in state-years with higher eviction rates (≥3500 evictions per 100,000 renter population; RR = 0.83, 95% CI 0.74, 0.93) compared to state-years with lower eviction rates (<3500 evictions per 100,000 renter population; RR = 0.91, 95% CI 0.81, 1.03). Overall, at the state-level, increased availability of affordable housing through the LIHTC program was associated with lower rates of IPV-related homicide. Increasing the availability of affordable housing may be one tool for preventing IPV-related homicide.


Disturbance and recovery of trunk mechanical and neuromuscular behaviors following repeated static trunk flexion: influences of duration and duty cycle on creep-induced effects.
Occupations involving frequent trunk flexion are associated with a higher incidence of low back pain. To investigate the effects of repeated static flexion on trunk behaviors, 12 participants completed six combinations of three static flexion durations (1, 2, and 4 min), and two flexion duty cycles (33% and 50%). Trunk mechanical and neuromuscular behaviors were obtained pre- and post-exposure and during recovery using sudden perturbations. A longer duration of static flexion and a higher duty cycle increased the magnitude of decrements in intrinsic stiffness. Increasing duty cycle caused larger decreases in reflexive muscle responses, and females had substantially larger decreases in reflexive responses following exposure. Patterns of recovery for intrinsic trunk stiffness and reflexive responses were consistent across conditions and genders, and none of these measures returned to pre-exposure values after 20 min of recovery. Reflexive responses may not provide a compensatory mechanism to offset decreases in intrinsic trunk stiffness following repetitive static trunk flexion. A prolonged recovery duration may lead to trunk instability and a higher risk of low back injury.


Composition and Diversity of Avian Communities Using a New Urban Habitat: Green Roofs.
Green roofs on buildings are becoming popular and represent a new component of the urban landscape. Public benefits of green roof projects include reduced stormwater runoff, improved air quality, reduced urban heat island effects, and aesthetic values. As part of a city-wide plan, several green roofs have been constructed at Chicago's O'Hare International Airport (ORD). Like some other landscaping features, green roofs on or near an airport might attract wildlife and thus increase the risk of bird-aircraft collisions. During 2007-2011, we conducted a series of studies to evaluate wildlife use of newly constructed green roofs and traditional (gravel) roofs on buildings at ORD. These green roofs were 0.04-1.62 ha in area and consisted of primarily stonecrop species for vegetation. A total of 188 birds were observed using roofs during this research. Of the birds using green roofs, 66, 23, and 4 % were Killdeer, European Starlings, and Mourning Doves, respectively. Killdeer nested on green roofs, whereas the other species perched, foraged, or loafed. Birds used green roofs almost exclusively between May and October. Overall, avian use of the green roofs was minimal and similar to that of buildings with traditional roofs. Although green roofs with other vegetation types might offer forage or cover to birds and thus attract potentially hazardous wildlife, the stonecrop-vegetated green roofs in this study did not increase the risk of bird-aircraft collisions.


Isolation of a higher eukaryotic telomere from Arabidopsis thaliana.
We have developed a method for constructing genomic libraries enriched for telomeric DNA sequences, enabling the isolation of telomeres from higher eukaryotic organisms with large chromosomes. The method was used to clone telomeric DNA sequences from the flowering plant Arabidopsis thaliana. A. thaliana telomeres are composed primarily of tandemly repeated blocks of the sequence 5'-CCCTAAA-3' and are heterogeneous in size. Genomic sequences that cross-hybridize at high stringency with A. thaliana telomeric repeats are present in other higher plants. In Zea mays (corn), these cross-hybridizing sequences are located at the telomeres. In addition, the A. thaliana telomeric repeats cross-hybridize at low stringency to genomic sequences located at the telomeres of human chromosomes.