Population Genomics of Bettongia lesueur: Admixing Increases Genetic Diversity with no Evidence of Outbreeding Depression.
Small and isolated populations are subject to the loss of genetic variation as a consequence of inbreeding and genetic drift, which in turn, can affect the fitness and long-term viability of populations. Translocations can be used as an effective conservation tool to combat this loss of genetic diversity through establishing new populations of threatened species, and to increase total population size. Releasing animals from multiple genetically diverged sources is one method to optimize genetic diversity in translocated populations. However, admixture as a conservation tool is rarely utilized due to the risks of outbreeding depression. Using high-resolution genomic markers through double-digest restriction site-associated sequencing (ddRAD-seq) and life history data collected over nine years of monitoring, this study investigates the genetic and fitness consequences of admixing two genetically-distinct subspecies of Bettongia lesueur in a conservation translocation. Using single nucleotide polymorphisms (SNPs) identified from 215 individuals from multiple generations, we found an almost 2-fold increase in genetic diversity in the admixed translocation population compared to the founder populations, and this was maintained over time. Furthermore, hybrid class did not significantly impact on survivorship or the recruitment rate and therefore we found no indication of outbreeding depression. This study demonstrates the beneficial application of mixing multiple source populations in the conservation of threatened species for minimizing inbreeding and enhancing adaptive potential and overall fitness.


Cysteinyl-leukotriene receptors and cellular signals.
Cysteinyl-leukotrienes (cysteinyl-LTs) exert a range of proinflammatory effects, such as constriction of airways and vascular smooth muscle, increase of endothelial cell permeability leading to plasma exudation and edema, and enhanced mucus secretion. They have proved to be important mediators in asthma, allergic rhinitis, and other inflammatory conditions, including cardiovascular diseases, cancer, atopic dermatitis, and urticaria. The classification into subtypes of the cysteinyl-LT receptors (CysLTRs) was based initially on binding and functional data, obtained using the natural agonists and a wide range of antagonists. CysLTRs have proved remarkably resistant to cloning. However, in 1999 and 2000, the CysLT1R and CysLT2R were successfully cloned and both shown to be members of the G-protein coupled receptors (GPCRs) superfamily. Molecular cloning has confirmed most of the previous pharmacological characterization and identified distinct expression patterns only partially overlapping. Recombinant CysLTRs couple to the Gq/11 pathway that modulates inositol phospholipids hydrolysis and calcium mobilization, whereas in native systems, they often activate a pertussis toxin-insensitive Gi/o-protein, or are coupled promiscuously to both G-proteins. Interestingly, recent data provide evidence for the existence of an additional receptor subtype that seems to respond to both cysteinyl-LTs and uracil nucleosides, and of an intracellular pool of CysLTRs that may have roles different from those of plasma membrane receptors. Finally, a cross-talk between the cysteinyl-LT and the purine systems is being delineated. This review will summarize recent data derived from studies on the molecular and cellular pharmacology of CysLTRs.


Activation of STAT transcription factors by herpesvirus Saimiri Tip-484 requires p56lck.
Signal transducers and activators of transcription (STATs) relay signals from activated cell surface receptors directly to the nucleus. Previously, a protein required for T-cell transformation by the DNA tumor virus herpesvirus saimiri (HVS) and designated tyrosine kinase interacting protein (Tip-484) was shown to interact with and dramatically upregulate the activity of p56lck. p56lck is a nonreceptor tyrosine kinase that is essential for signaling by the T-cell receptor and also interacts with the CD4, CD8, and interleukin-2 receptors. The present data show activation of STAT1 and -3 by Tip-484. STAT1 and -3 were also found to complex with glutathione S-transferase-Tip-484 only in the presence of p56lck, and STAT3 was shown to be phosphorylated by the Tip-484-p56lck multiprotein complex in vitro. Infection of T cells with HVS or expression of recombinant Tip-484 significantly increased the DNA-binding activity of the STAT1 and STAT3 transcription factors in nuclear extracts and also increased the phosphorylation of STAT3 in vivo. This is the first report of STAT activation by a DNA tumor virus protein. Moreover, these studies demonstrate that p56lck is required for STAT activation by Tip-484.


Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways.
Ergosterol peroxide (EP), a sterol derived from medicinal mushrooms, has been reported to exert antitumor activity in several tumor types. However, the role of EP toward ovarian cancer cells has not been investigated. In this study, we analyzed the cytotoxicity of EP in various cell lines representing high-grade serous ovarian cancer and low-grade serous ovarian cancer, respectively. Although EP showed no significant inhibition of the viability of normal ovarian surface epithelial cells, it impaired the proliferation and invasion capacities of tumor cells in a dose-dependent manner. We further figured out key modulators involved in its antitumor effects by quantitative reverse transcription polymerase chain reaction, ELISA, and Western blot. The nuclear β-catenin was down-regulated upon EP treatment, subsequently reducing the Cyclin D1 and c-Myc expression levels. Meanwhile, the protein level of protein tyrosine phosphatase SHP2 was up-regulated in EP treated cells, whereas Src kinase activity was inhibited. Both activation of SHP2 phosphatase and inhibition of Src kinase decreased the phosphorylation level of transducer and activator of STAT3 protein, which was implicated in oncogenesis. On the other hand, EP remarkably inhibited the expression and secretion of VEGF-C, implying its involvement in counteracting tumor angiogenesis. Moreover, EP treatment showed comparable cytotoxic effect with β-catenin knock-down or STAT3 inhibition. Taken together, our results demonstrated that EP showed antitumor effects toward ovarian cancer cells through both β-catenin and STAT3 signaling pathways, making it a promising candidate for drug development.


Analysis of cystic fibrosis transmembrane regulator and azoospermia factor polymorphisms in infertile men in relation to other abnormalities.
The aim was to determine the prevalence of compound genetic abnormalities in patients who are carriers of cystic fibrosis transmembrane regulator (CFTR) gene polymorphism and to compare our results with similar patients reported in the literature. One hundred and nine patients were identified to be carriers of CFTR gene polymorphism. Additional genetic testing for karyotype abnormalities or Y chromosome microdeletions (YMD) was performed. Three patients (2.75%) of 109 were identified to have compound genetic abnormalities. One patient had 5T/5T while the other had 6T/6T and the third had 9T/9T. The three patients had deletions of azoospermia factor regions (AZFa+b or AZFa+b+c). There were no karyotype abnormalities identified in our database. In the literature, four patients with compound CFTR mutations and YMD were identified, in three patients had karyotype abnormalities. In conclusion, compound genetic abnormalities in CFTR mutation patients can be a contributing factor when abnormal spermatogenesis is encountered.


Ultrasound Pixel-Based Beamforming With Phase Alignments of Focused Beams.
We previously developed unified pixel-based (PB) beamforming to generate high-resolution sonograms, based on field pattern analysis. In this framework, we found that the transmit waveshape away from the focus could be characterized by two spherical pulses. These correspond to the maximal and minimal distances from the imaging point to the active aperture. The beamformer uses this model to select the highest energy signals from backscattered data. A spatiotemporal interpolation formula is used to provide a smooth transition in regions near the focal depth where there is no dominant reflected pulse. In this paper, we show that the unified PB approach is less robust at lower center frequencies. The interpolated data is suboptimal for a longer transmit waveshape. As a result, the spatial resolution at the focal depth is lower than that in other regions. By further exploring the field pattern, we propose a beamformer that is more robust to variations in beamwidth. The new method, named coherent PB beamforming, aligns and compounds the pulse data directly in the transition regions. In simulation and phantom studies, the coherent PB approach is shown to outperform the unified PB approach in spatial resolution. It helps regain optimal resolution at the focal depth while still maintaining good image quality in other regions. We also demonstrate the new method on in vivo data where its improvements over the unified PB method are demonstrated on scanned objects with a more complicated structure.


[Impact of tuberculosis patient's attitude towards their disease on therapeutical efficiency].
The paper analyzes the factors that form the types of the patients' feelings of their disease and provides evidence for the impact of their attitude towards the disease on treatment outcomes. The paper gives a prognostic table for early determination of whether the patients can stop their therapy ahead of schedule.


Some methodological studies on effector cells in the lymphocyte-dependent cytotoxic antibody assay.
A method of direct freezing was found to be reliable for storage of the effectors for the LDA assay, though there is a considerable loss of cells. In order to get immunologically active K cells after thawing, an important step is to leave the cells to recuperate overnight in an appropriate medium before use. A short-term storage of fresh effectors is also possible. The use of a pool of effector cells from a minimum of 3 random blood donors obviates the selection of HL-A types furthermore permits a saving of the amount of serum used. Enrichment of a B cell population by removing the cells capable of forming spontaneous rosettes with SRBC was not found to enhance cytotoxicity. Pretreatment of cells with pronase, trypsin and neuraminidase did not significantly enhance their effector activity, while papain treated cells showed a systematically increased specific lysis.


Alcohol-related liver disease: treatment controversies.
The therapy of alcohol-related liver disease remains relatively unsatisfactory despite years of research designed to understand the pathogenesis of alcoholic liver injury and the processes involved in recovery from alcohol-related liver injury. Drugs such as the corticosteroids and colchicine appear to have a place in the management of some patients with alcohol-related liver disease but their use is not widespread in clinical practice. Liver transplantation has become an increasingly used therapy in patients with advanced liver disease but the enthusiasm of the early 1990s is now being replaced by a more cautious approach, particularly to those who have not abstained from alcohol for a significant period prior to transplant assessment. The brightest area in any discussion of treatment approaches to alcoholic liver disease is that of predicting the future. A number of agents designed to modify the inflammatory response and the endotoxaemia associated with significant alcoholic liver injury may be more beneficial than current drugs used for severe alcoholic hepatitis or cirrhosis. As in all discussions of alcohol-related liver disease and its management, it is important to highlight the need to exclude other forms of liver injury in patients who drink heavily as those diseases respond more to specific therapies than does alcoholic liver disease. The underlying therapy for all patients with alcoholic liver disease is abstinence from alcohol and the importance of encouraging patients to cease their damaging intake of alcohol can not be overemphasised.


Effect of Low-Dose Alcohol Consumption on Inflammation Following Transient Focal Cerebral Ischemia in Rats.
Increasing evidence suggest that low-dose alcohol consumption (LAC) reduces the incidence and improves the functional outcome of ischemic stroke. We determined the influence of LAC on post-ischemic inflammation. Male Sprague-Dawley rats were divided into 3 groups, an ethanol (13.5% alcohol) group, a red wine (Castle Rock Pinot Noir, 13.5% alcohol) group, and a control group. The amount of alcohol given to red wine and ethanol groups was 1.4 g/kg/day. After 8 weeks, the animals were subjected to a 2-hour middle cerebral artery occlusion (MCAO) and sacrificed at 24 hours of reperfusion. Cerebral ischemia/reperfusion (I/R) injury, expression of adhesion molecules and pro- and anti-inflammatory cytokines/chemokines, microglial activation and neutrophil infiltration were evaluated. The total infarct volume and neurological deficits were significantly reduced in red wine- and ethanol-fed rats compared to control rats. Both red wine and ethanol suppressed post-ischemic expression of adhesion molecules and microglial activation. In addition, both red wine and ethanol upregulated expression of tissue inhibitor of metalloproteinases 1 (TIMP-1), downregulated expression of proinflammatory cytokines/chemokines, and significantly alleviated post-ischemic expression of inflammatory mediators. Furthermore, red wine significantly reduced post-ischemic neutrophil infiltration. Our findings suggest that LAC may protect the brain against its I/R injury by suppressing post-ischemic inflammation.


The effect of aerobic soil conditions, soil volume and sowing date on the development of four tropical rice varieties grown in the greenhouse.
Rice has generally been reported to yield less in aerobic soil conditions than in flooded soil conditions, in association with delayed anthesis and a reduction in height. A greenhouse experiment was conducted and repeated twice with four rice varieties grown in either flooded or nearly-saturated aerobic soil, in either large or small pots. The rate of leaf appearance was recorded weekly until heading time, when plants were harvested for shoot and root biomass. The kinetics of leaf appearance was generally trilinear with longer phyllochrons in the May sowing. Pot size had only a small effect whereas aerobic soil conditions slowed down the rate of leaf initiation, which consequently delayed panicle initiation and heading date and thus increased the duration of the tillering phase and finally the number of tillers. Surprisingly, the four varieties showed a significant response to sowing date, especially IR72, which headed 21 days later and after the expansion of two more leaves in the May sowing. The aerobic soil conditions and sowing date have thus changed the rate of development of rice plants and this trait has appeared to be the initial link of a chain of consequences in a series of traits known to be affected by these factors.


Perinatal maternal high-fat diet induces early obesity and sex-specific alterations of the endocannabinoid system in white and brown adipose tissue of weanling rat offspring.
Perinatal maternal high-fat (HF) diet programmes offspring obesity. Obesity is associated with overactivation of the endocannabinoid system (ECS) in adult subjects, but the role of the ECS in the developmental origins of obesity is mostly unknown. The ECS consists of endocannabinoids, cannabinoid receptors (cannabinoid type-1 receptor (CB1) and cannabinoid type-2 receptor (CB2)) and metabolising enzymes. We hypothesised that perinatal maternal HF diet would alter the ECS in a sex-dependent manner in white and brown adipose tissue of rat offspring at weaning in parallel to obesity development. Female rats received standard diet (9 % energy content from fat) or HF diet (29 % energy content from fat) before mating, during pregnancy and lactation. At weaning, male and female offspring were killed for tissue harvest. Maternal HF diet induced early obesity, white adipocyte hypertrophy and increased lipid accumulation in brown adipose tissue associated with sex-specific changes of the ECS's components in weanling rats. In male pups, maternal HF diet decreased CB1 and CB2 protein in subcutaneous adipose tissue. In female pups, maternal HF diet increased visceral and decreased subcutaneous CB1. In brown adipose tissue, maternal HF diet increased CB1 regardless of pup sex. In addition, maternal HF diet differentially changed oestrogen receptor across the adipose depots in male and female pups. The ECS and oestrogen signalling play an important role in lipogenesis, adipogenesis and thermogenesis, and we observed early changes in their targets in adipose depots of the offspring. The present findings provide insights into the involvement of the ECS in the developmental origins of metabolic disease induced by inadequate maternal nutrition in early life.


Spirulina versicolor improves insulin sensitivity and attenuates hyperglycemia-mediated oxidative stress in fructose-fed rats.
The current study aimed to investigate the anti-hyperglycemic, anti-hyperlipidemic and insulin sensitizing effects of the cyanobacterium Spirulina versicolor extract in fructose-fed rats. Rats were fed 30% fructose solution in drinking water for 4 weeks. Animals exhibited hyperglycemia and hyperinsulinemia were selected for further investigations. Diabetic and control rats were orally supplemented with 50 mg/kg body weight S. versicolor extract for 4 weeks. At the end of 8 weeks, fructose-fed rats showed a significant increase in serum glucose, insulin, cholesterol, triglycerides, cardiovascular risk indices and insulin resistance. Treatment of the fructose-fed rats with S. versicolor extract improved this metabolic profile. Fructose feeding produced a significant increase in serum tumor necrosis factor alpha and a decrease in adiponectin levels. In addition, fructose-fed rats exhibited a significant increase in liver, kidney and heart lipid peroxidation levels, and declined antioxidant defenses. Supplementation of the fructose-fed rats with S. versicolor extract reversed these alterations. S. versicolor attenuates hyperglycemia-mediated oxidative stress and inflammation, and is thus effective in improving insulin sensitivity in fructose-fed rats.


Comparisons of host specificity in feather louse genera (Insecta: Phthiraptera: Philopteridae) parasitizing gulls (Aves: Laridae: Larus).
Data from gene sequences and morphological structures were collected for the gull feather lice, Saemundssonia lari, Quadraceps punctatus, and Q. ornatus, parasitizing Larus crassirostris and L. schistisagus. Saemundssonia lari was collected from both gull species, and no detectable morphological and genetic differences were found between lice collected from the two different hosts. In contrast, Q. punctatus was only collected from L. crassirostris, whereas Q. ornatus was only collected from L. schistisagus. The two Quadraceps species were genetically highly divergent, and body-size differences corresponding to the gull's body size (Harrison's rule) were also detected between them. Both Quadraceps species were collected from the interbarb of the remex or rectrix, and a match in body size between the louse and the interbarb space may be important in escape from host preening defenses. In contrast, Saemundssonia is a head louse, inhabiting the finer feathers of the head and neck, which the bird cannot preen. A close match to host body size may be less important for lice in the head microhabitat. The differences in the pattern of host-specificity between Saemundssonia and Quadraceps on the two focal host species of this study were probably due to their different microhabitat preferences. More broadly, comparisons of the gene sequences of S. lari and Q. punctatus to those from other gull hosts showed that genetically almost undifferentiated populations of both species were distributed on wide range of gull species. Frequent interspecific hybridization of gulls is one possible factor that may allow these lice to maintain gene flow across multiple host species.


Hyperglycemia promotes microinflammation as evaluated by C-reactive protein in the very elderly.
C-reactive protein (CRP) is not only an acute phase reactant but also a sensitive marker of subclinical inflammation associated with atherosclerosis. The aim of the present study was to determine whether glycemic control or blood pressure influences the vascular microinflammation as evaluated by CRP levels in the very elderly. The study group consisted of 195 residents aged 85 years. The subjects were divided into three groups according to their CRP levels; a low (<1 mg/L), an average (1 to 3 mg/L), and a high (3 to 10 mg/L) CRP group. Hemoglobin A(1c) (HbA(1c)) levels were used as an index of glycemic control. The HbA(1c) level showed a significant positive correlation with the CRP level (r=0.289, p<0.0001). In contrast, systolic and diastolic blood pressures failed to correlate with the CRP level. The HbA(1c) was significantly greater in the high CRP group compared to the average and the low CRP groups (6.01+/-0.29%, 5.57+/-0.09% and 5.42+/-0.05%, respectively). Furthermore, the HbA(1c) adjusted by sex, body mass index, systolic blood pressure, serum triglyceride and current smoking status was significantly higher in the high CRP group than in the average and the low CRP groups. Multiple regression analysis also revealed that the HbA(1c) level was significantly and independently associated with the CRP level. These results suggest that tight good glycemic control, even in very elderly subjects, may be able to reduce the systemic inflammation that contributes to leads to atherosclerosis.


Strain differentiation in Bacteroides fragilis by RAPD and Dendron computer-assisted gel analysis.
Batteroides fragilis is the anaerobe most frequently isolated from human infections. Strains of this species are not easily distinguished by phenotypic tests. It is important to make this distinction because virulence may vary between strains and because B. fragilis seems to be a heterogeneous species. The aim of this study was to assess the utility of randomly amplified polymorphic DNA (RAPD) analysis for differentiation of 46 strains of B. fragilis. Twenty-seven of the strains belonged to Johnson's DNA homology group I and 8 to group II, while 11 strains had not been assigned to any of these groups (NI group). The primers OPA16 and 18 were chosen among 30 primers tested for optimal RAPD analysis. OPA18 gave best discrimination, revealing a total of 15 genotypes while OPA16 gave 13. The gels obtained after RAPD analysis were evaluated with the Dendron computer-assisted program. Most strains showed similarity levels (S(AB)) within 70%. Strain clusters thus established were not always in agreement with DNA homology since strains from both homology groups fell in the same cluster. Similarly, strains of the NI group fell among the group I and II homology strains. RAPD was useful for differentiation of B. fragilis strains and thus probably suitable for epidemiological studies. On the other hand, DNA-DNA homology, comparing the entire genome of strains rather than a few random priming sites, would be more reliable for taxonomy. Computer-assisted gel analysis made it possible to objectively evaluate multiple banding patterns, thereby increasing the reliability of the RAPD analysis.


Baseline magnetic resonance imaging of the optic nerve provides limited predictive information on short-term recovery after acute optic neuritis.
In acute optic neuritis, magnetic resonance imaging (MRI) may help to confirm the diagnosis as well as to exclude alternative diagnoses. Yet, little is known on the value of optic nerve imaging for predicting clinical symptoms or therapeutic outcome. To evaluate the benefit of optic nerve MRI for predicting response to appropriate therapy and recovery of visual acuity. Clinical data as well as visual evoked potentials (VEP) and MRI results of 104 patients, who were treated at the Department of Neurology with clinically definite optic neuritis between December 2010 and September 2012 were retrospectively reviewed including a follow up within 14 days. Both length of the Gd enhancing lesion (r = -0.38; p = 0.001) and the T2 lesion (r = -0.25; p = 0.03) of the optic nerve in acute optic neuritis showed a medium correlation with visual acuity after treatment. Although visual acuity pre-treatment was little but nonsignificantly lower if Gd enhancement of the optic nerve was detected via orbital MRI, improvement of visual acuity after adequate therapy was significantly better (0.40 vs. 0.24; p = 0.04). Intraorbitally located Gd enhancing lesions were associated with worse visual improvement compared to canalicular, intracranial and chiasmal lesions (0.35 vs. 0.54; p = 0.02). Orbital MRI is a broadly available, valuable tool for predicting the improvement of visual function. While the accurate individual prediction of long-term outcomes after appropriate therapy still remains difficult, lesion length of Gd enhancement and T2 lesion contribute to its prediction and a better short-term visual outcome may be associated with detection and localization of Gd enhancement along the optic nerve.


Genistein induces cytokinesis failure through RhoA delocalization and anaphase chromosome bridging.
Genistein, an isoflavone abundantly present in soybeans, possesses anticancer properties and induces growth inhibition including cell cycle arrest and apoptosis. Although abnormal cell division, such as defects in chromosome segregation and spindle formation, and polyploidization have been described, the mechanisms underlying the induction of abnormal cell division are unknown. In this study, we examined the effect of genistein on cell division in cells that are synchronized in M phase, since genistein treatment delays mitotic entry in asynchronous cells. HeLa S3 cells were arrested at the G2 phase and subsequently released into the M phase in presence of genistein. Immunofluorescence staining showed that genistein treatment delays M phase progression. Time-lapse analysis revealed that the delay occurs until anaphase onset. In addition, genistein treatment induces cleavage furrow regression, resulting in the generation of binucleated cells. Central spindle formation, which is essential for cytokinesis, is partially disrupted in genistein-treated cells. Moreover, aberrant chromosome segregation, such as a chromosome bridge and lagging chromosome, occurs through progression of cytokinesis. RhoA, which plays a role in the assembly and constriction of an actomyosin contractile ring, is delocalized from the cortex of the ingressing cleavage furrow. These results suggest that genistein treatment induces binucleated cell formation through cleavage furrow regression, which is accompanied by chromosome bridge formation and RhoA delocalization. Our results provide the mechanism that underlies genistein-induced polyploidization, which may be involved in genistein-induced growth inhibition.


Non-high-density lipoprotein cholesterol: why lower is better.
Recent comparative trials of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) suggest that lower is better and that reducing low-density lipoprotein cholesterol (LDL-C) levels to below 100 mg/dL can provide additional clinical benefit. Non-high-density lipoprotein cholesterol (non-HDL-C) contains more atherogenic cholesterol than LDL-C and is considered a more accurate measurement of the total amount of atherogenic particles in the circulation. Therefore, the principle that "lower is better" may also apply to lowering levels of non-HDL-C. In persons with high triglycerides (200-499 mg/dL), LDL-C remains the primary target of therapy, but non-HDL-C is an important secondary therapeutic target. Non-HDL-C is strongly correlated with small dense LDL as well as apolipoprotein B, an established predictor of cardiovascular disease risk. Current evidence indicates that statins not only rapidly and dramatically reduce LDL-C, but also have a similar effect on non-HDL-C, and that the greater the reduction in LDL-C, the greater will be the reduction in non-HDL-C.


A photosensory two-component system regulates bacterial cell attachment.
Flavin-binding LOV domains are blue-light photosensory modules that are conserved in a number of developmental and circadian regulatory proteins in plants, algae, and fungi. LOV domains are also present in bacterial genomes, and are commonly located at the amino termini of sensor histidine kinases. Genes predicted to encode LOV-histidine kinases are conserved across a broad range of bacterial taxa, from aquatic oligotrophs to plant and mammalian pathogens. However, the function of these putative prokaryotic photoreceptors remains largely undefined. The differentiating bacterium, Caulobacter crescentus, contains an operon encoding a two-component signaling system consisting of a LOV-histidine kinase, LovK, and a single-domain response regulator, LovR. LovK binds a flavin cofactor, undergoes a reversible photocycle, and displays increased ATPase and autophosphorylation activity in response to visible light. Deletion of the response regulator gene, lovR, results in severe attenuation of cell attachment to a glass surface under laminar flow, whereas coordinate, low-level overexpression of lovK and lovR results in a light-independent increase in cell-cell attachment, a response that requires both the conserved histidine phosphorylation site in LovK and aspartate phosphorylation site in LovR. Growing C. crescentus in the presence of blue light dramatically enhances cell-cell attachment in the lovK-lovR overexpression background. A conserved cysteine residue in the LOV domain of LovK, which forms a covalent adduct with the flavin cofactor upon absorption of visible light, is necessary for the light-dependent regulation of LovK enzyme activity and is required for the light-dependent enhancement of intercellular attachment.


The Development of the "Telislife" Questionnaire for the Evaluation of Telephone Use in Cochlear Implant Users.
Purpose For cochlear implant users, the ability to use the telephone is often seen as an important landmark during rehabilitation and an indicator of cochlear implant benefit. The goal of this study was to develop a short questionnaire exploring the ability to use the telephone in cochlear implant users, named Telislife, and test it in a group of experienced users. Method This prospective multicenter study was based on the completion of self-administrated questionnaires. The Telislife includes 20 items using a 5-point Likert scale for answers. Speech recognition scores were obtained with monosyllabic word lists at 70 dB HL. Quality of life was evaluated with the Nijmegen Cochlear Implant Questionnaire. This study included 55 adult patients wearing a cochlear implant for over 1 year. Results The Telislife questionnaire showed excellent reliability (Cronbach's α = .91). A significant correlation was found between Telislife scores and Nijmegen Cochlear Implant Questionnaire scores (r = .69, p < .001) and speech recognition scores (r = .35, p = .007). Conclusion Given significant correlations between Telislife scores and both speech recognition and quality of life and given its short form, the Telislife questionnaire appears to be a reliable tool to evaluate cochlear implant outcomes in clinical practice. Supplemental Material https://doi.org/10.23641/asha.13322873.


Naturalizing unnatural death in Los Angeles County jails.
In this paper we use quantitative and qualitative methods to examine how death investigations in Los Angeles County jails disproportionately naturalize death among Black and Latino incarcerated people. Our study is based on an assessment of 58 autopsies, coroner investigator narratives, and toxicology reports produced between 2009 and 2018. We found that the Medical Examiner frequently arrived at natural or undetermined death determinations that minimized the culpability of carceral staff for loss of life that occurred within county jail. In our dataset, Black people were disproportionately classified as natural. Undetermined deaths were almost exclusively Latino. More than 75% of the cases in our study were deaths that occurred before standing trial. Our findings reveal how biomedical knowledge about incarcerated Black and Latino people is used to erase the life-diminishing effects of punishment, neglect, and maltreatment that are central to the project of mass incarceration.


[Total antioxidant activity of the lacrimal fluid].
Total antioxidant activity of the lacrimal fluid (TAALF) was studied by luminol-dependent iron-induced chemiluminescence in an original model system on citrate phosphate buffer. Total antioxidant activity was estimated in percent of control (light sum of the model system fluorescence). The mean decrease of the light sum of the model system fluorescence in the presence of normal human lacrimal fluid supernatant was more than 50%, in glaucoma 67.2 +/- 4.43%, in cataract 58.5 +/- 2.61%, and in uveitis 76.9 +/- 1.13% of control. Traditional therapy of uveitis was associated with an increase of TAALF. Use of the proposed method for TAALF evaluation together with clinical data allows justified and individual antioxidant treatment of patients with ocular diseases and helps monitor the treatment efficiency. The study is noninvasive, cheap, and simple, which recommends evaluation of TAALF in clinical practice as a rapid test indicating the level of free radical oxidation in ocular tissues.


Otoacoustic emissions in patients with retrocochlear dysfunction: a report of five cases.
This article describes the results of otoacoustic emissions testing in five patients with sensorineural hearing loss. We conducted an audiologic evaluation and performed image and cerebral function studies on each patient. Our investigation revealed that all five had spontaneous otoacoustic emissions and/or distortion product otoacoustic emissions. Pharmacologic treatment with anxiolytics, antidepressants, and anticonvulsant drugs was successful in alleviating symptoms in three patients. An organic and a central functional cause of symptoms was found in the remaining two patients. Before pharmacologic therapy, the spontaneous otoacoustic emissions were of high intensity, and the distortion product emissions were minimal. Following drug therapy, the former disappeared and the latter appeared.


Zebrafish models of human liver development and disease.
The liver performs a large number of essential synthetic and regulatory functions that are acquired during fetal development and persist throughout life. Their disruption underlies a diverse group of heritable and acquired diseases that affect both pediatric and adult patients. Although experimental analyses used to study liver development and disease are typically performed in cell culture models or rodents, the zebrafish is increasingly used to complement discoveries made in these systems. Forward and reverse genetic analyses over the past two decades have shown that the molecular program for liver development is largely conserved between zebrafish and mammals, and that the zebrafish can be used to model heritable human liver disorders. Recent work has demonstrated that zebrafish can also be used to study the mechanistic basis of acquired liver diseases. Here, we provide a comprehensive summary of how the zebrafish has contributed to our understanding of human liver development and disease.


Role of Histamine-releasing Factor in Allergic Inflammatory Reactions.
Mast cells are effector cells in immunoglobulin E (IgE)-mediated immediate hypersensitivity and allergic diseases such as asthma and food allergy. Mast cells are activated by the aggregation of the IgE-bound high-affinity IgE receptor FcεRI with multivalent antigen. Activated mast cells secrete proinflammatory mediators such as histamine, serotonin, and proteases and produce cytokines and chemokines. However, it has been reported that mast cells are activated by crosslinking of FcεRI with monomeric IgE in the absence of antigen. We have recently demonstrated that histamine-releasing factor (HRF) is involved in IgE-mediated mast cell activation both in vitro and in vivo. HRF binds to a subset of IgE and IgG molecules [HRF-reactive antibodies (Abs)]. The Fab, but not Fc, portions of the IgE and IgG molecules are HRF-binding sites, and the N-terminal 19-residue (N19) and H3 portions of HRF are HRF-reactive Ab-binding sites. We observed that both N19 and H3 tagged with glutathione S transferase (GST) (GST-N19 and GST-H3) can inhibit the interaction between HRF and HRF-reactive Abs. Using acute- and late-phase passive cutaneous anaphylaxis mouse models, it was shown that HRF initiates mast cell activation through HRF-reactive, but not HRF-nonreactive, IgE in vivo. Antigen-induced passive cutaneous anaphylaxis was inhibited by pretreatment with GST-N19 and GST-H3. We demonstrated that pretreatment with GST-N19 before antigen challenge inhibited antigen-induced mast cell-dependent airway inflammation. In addition, GST-N19 partially inhibited Aspergillus fumigatus extract-induced IgE-dependent airway inflammation. However, GST-N19 did not inhibit T cell-dependent airway inflammation. These results suggest that mast cells are target cells for HRF to initiate IgE- and mast cell-dependent airway inflammation.


[Helicobacter pylori infection in 755 patients with digestive complaints: Pasteur Institute, Morocco, 1998-2007].
We determined the prevalence of Helicobacter pylori infection in 755 patients with digestive complaints identified from laboratory records at the Pasteur Institute, Morocco from 1998 to 2007. Epidemiological factors and gastrointestinal conditions associated with this infection were also studied. All patients underwent endoscopy and diagnosis was by histology examination. The prevalence of H. pylori infection was 69%. The difference in prevalence between the age group 40-50 years and other age groups was statistically significant; gender had no significant association. H. pylori infection was found in 92% of chronic gastritis cases. The prevalence of H. pylori was significantly higher in the antrum (73%) than in the corpus (21%) and the pylorus (6%).


Preschoolers distribute scarce resources according to the moral valence of recipients' previous actions.
Children aged 3 years and 4½ years old watched a puppet, struggling to achieve goals, who was helped by a 2nd puppet and violently hindered by a 3rd. The children then distributed wooden biscuits between the helper and hinderer. In Experiment 1, when distributing a small odd number of biscuits, 4½-year-olds (N = 16) almost always gave more to the helper. Children verbally justified their unequal distributions by reference to the helper's prosocial behavior or the hinderer's antisocial behavior. In Experiment 2, when biscuits were more plentiful, 4½-year-olds (N = 16) usually gave equal numbers to helper and hinderer, indicating that 4½-year-olds usually preferred not to distribute unequally unless forced to by resource scarcity. Three-year-olds (N = 16 in Experiment 1, N = 20 in Experiment 3) gave more biscuits equally often to the helper and to the hinderer. In many cases, this was because they were confused as to the identities and actions of the puppets, possibly because they were shocked by the hinderer's actions. Two fundamental moral behaviors are therefore demonstrated in young preschoolers: indirect reciprocity of morally valenced acts and a preference for equality when distributing resources, although the cognitive bases for these behaviors remain unclear. These results join other recent studies in demonstrating that the seeds of complex moral understanding and behavior are found early in development.


Perspectives from Spanish infectious diseases professionals on 2009 A (H1N1) influenza: the third half.
The first influenza pandemic in more than 40 years was declared in 2009. We aimed to evaluate the beliefs of Spanish infectious diseases professionals regarding several aspects of 2009 A (H1N1) influenza once the epidemic waned. An online survey was designed and distributed among members of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). The survey considered hospital organization and preparedness planning and conduct, as well as the opinion of the infectious diseases professionals regarding several key issues. Between 7 March and 22 March 2010, 303 responses, corresponding to 12.8% of the SEIMC membership, were received. Of the respondents, 48.2% were microbiologists and 42.3% were clinicians dealing with infectious diseases. Forty-one per cent of respondents did not believe that 2009 A (H1N1) influenza had a more severe presentation than other seasonal influenzas. Only 5% fully agreed that 2009 A (H1N1) influenza had a more severe presentation. Influenza planning was available in 69.7% of represented institutions before the arrival of 2009 A (H1N1) influenza, and was considered to be useful, to different extents, by most professionals. In most institutions (88.3%), a multidisciplinary team was created to coordinate local pandemic influenza actions. The most successful protocols were those provided by regional healthcare authorities, followed by those from the CDC. The most problematic issues regarding 2009 A (H1N1) influenza were the management of patients in the emergency room and the vaccination and awareness of healthcare professionals (HCPs) regarding infection control. Microbiological diagnosis and the availability of antivirals were the least problematic areas. Although the majority of surveyed infectious diseases professionals did not believe that 2009 A (H1N1) influenza had an especially severe presentation, most of them agreed with the way that this epidemic was managed in their institutions.


Recommendations for lightning protection in sport.
Lightning is an important cause of weather-related morbidity and mortality and is often underrated. There has been an increase in the proportion of casualties occurring during outdoor sport and recreational activities over recent years. However, in Australia, there is a deficiency in recommendations for lightning safety at sporting events. Organisers of sporting events should have a lightning safety policy that includes a designated weather watcher with the authority to stop or postpone the event, a specific chain of command, and designated safe areas. Suspension and resumption of play should follow the "30/30" rule: play should stop when the flash-to-bang count is 30 seconds, and should not resume until 30 minutes after the last lightning. At events with large crowds, additional time should be allowed for evacuating all people to safe areas.


Mesenchymal stem cell-mediated endochondral ossification utilising micropellets and brief chondrogenic priming.
With limited autologous and donor bone graft availability, there is an increasing need for alternative graft substitutes. We have previously shown that chondrogenically priming mesenchymal stem cell (MSC) pellets for 28 d in vitro will reproducibly result in endochondral bone formation after in vivo implantation. However, pellet priming time for clinical applications is quite extensive. A micropellet (μpellet)-fibrin construct was developed and coupled, with a shorter priming period, determined by an in vitro time course experiment. In vitro data showed expression of chondrogenic genes and matrix production after 7 d of chondrogenic priming, indicating that briefer priming could possibly be used to induce bone formation in vivo. 7 and 28 d primed pellet, pellet-fibrin and μpellet-fibrin constructs were cultured for in vitro analysis and implanted subcutaneously for 8 weeks into nude mice. μpellet-fibrin constructs, cultured in vitro for 7 or 28 d, produced comparable bone to standard pellets in vivo. MSC-mediated bone formation was achieved following only 7 d of in vitro priming. Bone formation in vivo appeared to be influenced by overall matrix production pre-implantation. Given this short priming time and the injectable nature of the μpellet-fibrin constructs, this approach might be further developed as an injectable bone substitute, leading to a minimally-invasive treatment option, which would allow for tailored filling of bone defects.


Structural analysis of the subunits of the trehalose-6-phosphate synthase/phosphatase complex in Saccharomyces cerevisiae and their function during heat shock.
Synthesis of trehalose in the yeast Saccharomyces cerevisiae is catalysed by the trehalose-6-phosphate (Tre6P) synthase/phosphatase complex, which is composed of at least three different subunits encoded by the genes TPS1, TPS2, and TSL1. Previous studies indicated that Tps1 and Tps2 carry the catalytic activities of trehalose synthesis, namely Tre6P synthase (Tps1) and Tre6P phosphatase (Tps2), while TsI1 was suggested to have regulatory functions. In this study two different approaches have been used to clarify the molecular composition of the trehalose synthase complex as well as the functional role of its potential subunits. Two-hybrid analyses of the in vivo interactions of Tps1, Tps2, TsI1, and Tps3, a protein with high homology to TsI1, revealed that both TsI1 and Tps3 can interact with Tps1 and Tps2; the latter two proteins also interact with each other. In addition, trehalose metabolism upon heat shock was analysed in a set of 16 isogenic yeast strains carrying deletions of TPS1, TPS2, TSL1, and TPS3 in all possible combinations. These results not only confirm the previously suggested roles for Tps1 and Tps2, but also provide, for the first time, evidence that TsI1 and Tps3 may share a common function with respect to regulation and/or structural stabilization of the Tre6P synthase/phosphatase complex in exponentially growing, heat-shocked cells.


[Attention deficit hyperactivity disorder: its aetiological factors and endophenotypes].
Attention deficit hyperactivity disorder (ADHD) is one of the most frequent reasons for patients' visits in everyday practice. The academic and social distortion it produces in those affected by this condition have turned it into a subject that is receiving growing attention from researchers and the progress being made in the neurosciences means that it is being investigated from a wide range of approaches. Genetic aspects, as well as anatomical and neurobiological markers, are some of the new lines of research that are being used together with a more precise neuropsychological approach to obtain a more comprehensive understanding of ADHD. Such knowledge now involves genetic factors, centres of cognitive disorder and the search for endophenotypes that account for the complexity of its semiology. The primary cognitive deficits in ADHD appear to be the underlying problem in the disorder, special attention also being given to both the executive functions and the distortion of the capacity to inhibit responses. Furthermore, anatomical factors have been related to the type and severity of the symptomatology of the disorder, although the dispersion of the results and the genetic findings that focus their attention on anomalous alleles for dopamine transporting and receptor genes suggest that the disorder is more complex. The different aetiological factors that have been associated to the disorder and the variability in the semiology of ADHD place us before a situation in disarray; the determination of endophenotypes, however, could enable us carry out a better systematisation of a disorder that is currently still a long way from being fully understood.


Analysis of chronic aortic regurgitation by 2D and 3D echocardiography and cardiac MRI.
Purpose The study compares the feasibility of the quantitative volumetric and semi-quantitative approach for quantification of chronic aortic regurgitation (AR) using different imaging modalities. Methods Left ventricular (LV) volumes, regurgitant volumes (RVol) and regurgitant fractions (RF) were assessed retrospectively by 2D, 3D echocardiography and cMRI in 55 chronic AR patients. Semi-quantitative parameters were assessed by 2D echocardiography. Results 22 (40%) patients had mild, 25 (46%) moderate and 8 (14%) severe AR. The quantitative volumetric approach was feasible using 2D, 3D echocardiography and cMRI, whereas the feasibility of semi-quantitative parameters varied considerably. LV volume (LVEDV, LVESV, SVtot) analyses showed good correlations between the different imaging modalities, although significantly increased LV volumes were assessed by cMRI. RVol was significantly different between 2D/3D echocardiography and 2D echocardiography/cMRI but was not significantly different between 3D echocardiography/cMRI. RF was not statistically different between 2D echocardiography/cMRI and 3D echocardiography/cMRI showing poor correlations (r < 0.5) between the different imaging modalities. For AR grading by RF, moderate agreement was observed between 2D/3D echocardiography and 2D echocardiography/cMRI and good agreement was observed between 3D echocardiography/cMRI. Conclusion Semi-quantitative parameters are difficult to determine by 2D echocardiography in clinical routine. The quantitative volumetric RF assessment seems to be feasible and can be discussed as an alternative approach in chronic AR. However, RVol and RF did not correlate well between the different imaging modalities. The best agreement for grading of AR severity by RF was observed between 3D echocardiography and cMRI. LV volumes can be verified by different approaches and different imaging modalities.


Autoimmunity in the Elderly: Insights from Basic Science and Clinics - A Mini-Review.
Advancements in the field of biomedicine, including the control of infectious diseases through antibiotics and vaccination practices and the prevention of chronic disorders, have led to reduced mortality, increased life expectancy and, as such, growth of the older population. Ageing is accompanied by profound morphological and physiological alterations. In particular, the immune system undergoes a complex series of remodeling/restructuring events, involving almost all compartments - both the innate and the adaptive system. This process is termed immunosenescence or immune dysregulation and, basically, includes 3 events: a reduction in immune response, an increase in the inflammatory and oxidation background (inflammaging and oxi-inflammaging), and a production of autoantibodies. While there is an increase in autoimmunity in the elderly, this does not always translate into an increase in autoimmune diseases, which represent an important cause of morbidity and mortality and affect 5-10% of the world population. Each disease involves a specific age group. Generally speaking, most autoimmune diseases have a decreased peak age of onset, except for very few diseases such as giant cell arteritis and primary biliary cirrhosis, which are more prevalent among the elderly, or inflammatory bowel disease, which has 2 peaks of onset, the first one in young subjects and the other in those older than 60 years. Autoimmune disorders in the elderly have unique clinical presentations, and insidious and atypical symptoms may constitute a challenge for the physician. They are generally milder than in adults and can be controlled by a proper therapeutic treatment. However, despite advancements both in basic and clinical sciences, further studies and investigations are warranted and should be carried out in order to dissect the molecular framework induced by ageing.


Inhibition of muscarinic-coupled phosphoinositide hydrolysis by N-methyl-D-aspartate is dependent on depolarization via channel activation.
The intent of this work was to elucidate the mechanism by which N-methyl-D-aspartate (NMDA) receptor agonists inhibit a second messenger system, namely, the stimulation of phosphoinositide (PI) hydrolysis activated by muscarinic cholinergic receptor agonists. NMDA inhibited cholinergic stimulation of PI hydrolysis in a dose- and time-dependent manner. NMDA exerts this effect indirectly through channel activation, because both MK-801 and N-[1-(2-thienyl)cyclohexyl]piperidine (TCP) prevented this action. Prevention of the NMDA effect by removal of sodium, but not calcium, from the incubation buffer suggested that depolarization may be the responsible mechanism. Depolarization alone proved sufficient to inhibit cholinergic activation of PI hydrolysis, because both veratridine and an elevated extracellular potassium level inhibited cholinergic stimulation of PI hydrolysis. The effect of NMDA appeared to require sodium flux through NMDA channels rather than through voltage-dependent sodium channels, because tetrodotoxin failed to inhibit the effect of NMDA. In correlative electrophysiologic experiments, NMDA profoundly inhibited evoked excitatory postsynaptic potentials and population action potentials of CA1 neurons, an effect almost certainly due to depolarization. The dose and time course of the electrophysiologic effects correlated well with the biochemical effects. Taken together, the data support the assertion that NMDA receptor activation inhibits PI hydrolysis by depolarization mediated by sodium flux through NMDA channels.


Treatment Patterns for Chronic Obstructive Pulmonary Disease (COPD) in the United States: Results from an Observational Cross-Sectional Physician and Patient Survey.
There is a high prevalence of chronic obstructive pulmonary disease (COPD) in the United States (US). Although guidelines are available for the treatment of COPD, evidence suggests that management of COPD in clinical practice is not always aligned with this guidance. This study aimed to further understand the current use of COPD maintenance medication in the US. This study was an analysis of data from the Adelphi Respiratory Disease Specific Programme (DSP™) 2019. Point-in-time data were collected from participating US physicians and their COPD patients. Physicians were either primary care physicians (PCPs) or pulmonologists, with a minimum workload of ≥3 COPD patients per month. Patients were aged ≥18 years with a physician-confirmed diagnosis of COPD. In total, 171 physicians completed the survey (92 PCPs and 79 pulmonologists). Mean patient age was 66.4 years, 45% were female, with moderate COPD in 49.4% of patients and severe/very severe in 19.3%. Pulmonologists more frequently prescribed dual bronchodilation and triple therapy than PCPs, whereas inhaled corticosteroid/long-acting β2-agonist was more frequently prescribed by PCPs than pulmonologists. For both physician types, the most common reason for prescribing their patients' current treatment was 24-hour symptom relief. The majority of PCPs (70.1%) and pulmonologists (71.9%) reported referring to COPD guidelines when making treatment decisions. Prescribing patterns for COPD patients were found to differ between PCPs and pulmonologists. Improved physician understanding of how to tailor treatment for each patient, based on current symptoms and exacerbation risk, could help optimize patient care in COPD.


Phosphorus and iron deficiencies induce a metabolic reprogramming and affect the exudation traits of the woody plant Fragaria×ananassa.
Strawberries are a very popular fruit among berries, for both their commercial and economic importance, but especially for their beneficial effects for human health. However, their bioactive compound content is strictly related to the nutritional status of the plant and might be affected if nutritional disorders (e.g. Fe or P shortage) occur. To overcome nutrient shortages, plants evolved different mechanisms, which often involve the release of root exudates. The biochemical and molecular mechanisms underlying root exudation and its regulation are as yet still poorly known, in particular in woody crop species. The aim of this work was therefore to characterize the pattern of root exudation of strawberry plants grown in either P or Fe deficiency, by investigating metabolomic changes of root tissues and the expression of genes putatively involved in exudate extrusion. Although P and Fe deficiencies differentially affected the total metabolism, some metabolites (e.g. raffinose and galactose) accumulated in roots similarly under both conditions. Moreover, P deficiency specifically affected the content of galactaric acid, malic acid, lysine, proline, and sorbitol-6-phosphate, whereas Fe deficiency specifically affected the content of sucrose, dehydroascorbic acid, galactonate, and ferulic acid. At the same time, the citrate content did not change in roots under both nutrient deficiencies with respect to the control. However, a strong release of citrate was observed, and it increased significantly with time, being +250% and +300% higher in Fe- and P-deficient plants, respectively, compared with the control. Moreover, concomitantly, a significant acidification of the growth medium was observed in both treatments. Gene expression analyses highlighted for the first time that at least two members of the multidrug and toxic compound extrusion (MATE) transporter family and one member of the plasma membrane H(+)-ATPase family are involved in the response to both P and Fe starvation in strawberry plants.


Insulin B-chain reactive CD4+ regulatory T-cells induced by oral insulin treatment protect from type 1 diabetes by blocking the cytokine secretion and pancreatic infiltration of diabetogenic effector T-cells.
The mechanism of protection from type 1 diabetes conferred by regulatory T-cells induced by oral insulin treatment of NOD mice is not well understood. We demonstrate that oral insulin feeding of NOD mice induces the function of insulin B-chain reactive CD4+ regulatory T-cells, which compete with diabetogenic effector T-cells for the recognition of insulin in NOD.Scid recipient mice. These effector T-cells become deprived of interleukin (IL)-2 and interferon (IFN)-gamma and are unable to expand and migrate to the pancreas. Type 1 diabetes-protective splenic regulatory T-cells secrete relatively little transforming growth factor (TGF)-beta1, suggesting that TGF-beta may not contribute to the inactivation of effector T-cells in NOD.Scid recipients. The observed preferential infiltration of insulin-reactive regulatory T-cells rather than effector T-cells in the pancreas results in a nondestructive insulitis that correlates with an increased intrapancreatic expression of macrophage inflammatory protein-1beta. Thus, oral insulin therapy overcomes a deficiency in regulatory T-cells and protects against type 1 diabetes by inducing insulin B-chain reactive regulatory T-cells to block cytokine secretion and migration of diabetogenic effector T-cells to the pancreas. Our data emphasize that continuous oral insulin feeding over a prolonged period is required to prevent type 1 diabetes.


Release and actions of inhibitory prostaglandins from canine tracheal epithelium.
This study evaluated the sources and actions of inhibitory prostanoids on canine tracheal smooth muscle to determine if these accounted for epithelium derived relaxing factor activity. Concentration-response curves of canine tracheal smooth muscle were generated to carbachol in the presence and absence of the epithelium and (or) indomethacin, a cyclooxygenase inhibitor. Removal of the epithelium or addition of indomethacin (10(-5) M) in the presence of the epithelium shifted the curve significantly leftward compared with epithelial-intact tissue. Furthermore, addition of indomethacin to epithelial-denuded tissue produced the greatest shift in the curve. Removal of the epithelium increased contractility in response to electrical-field stimulation at intermediate frequencies compared with epithelium-intact tissues. The addition of indomethacin to epithelium-intact tissue also increased the contractile responses. Removal of the epithelium in the presence of indomethacin further increased responses. Radioimmunoassay of muscle bath fluid indicated that the inhibitory prostanoids prostaglandin I2 (PGI2) and prostaglandin E2 (PGE2) were released. PGI2 was released from the epithelium as well as from a nonepithelial source. PGE2 was released from the epithelium in response to electrical-field stimulation. The release of PGE2 was greatly reduced by the addition of indomethacin (10(-5) M), but not by the addition of omega-conotoxin (GVIA), an N-type Ca2+ channel antagonist, nor by the addition of tetrodotoxin, a Na+ channel blocker. Both toxins abolished contractions to electrical-field stimulation. We conclude that the inhibitory prostanoids PGI2 and PGE2 are released, along with a nonprostanoid factor from epithelium, and modulate airway smooth muscle contractility to stimulation of cholinergic nerves and muscarinic agonists. PGE2 is released from epithelium by electrical-field stimulation independent of nerve function.


[The detection of changes in intra-atrial conductivity (based on enhanced ECG data)].
The 20-fold enhanced ECG (without frequency filtration of the signal) was recorded in 30 normal men aged 18 to 36 years. A study was made of the constancy of the P wave forms on the ECG. The P wave form underwent changes in 8 test subjects: in 5 during breathing retention on expiration and in 3 during superficial breathing. The changes indicated are viewed as a manifestation of intraatrial conduction disorders. It is assumed that the changes in the tone of the autonomic nervous system and myocardial hypoxia may contribute to the detection of latent disorders in the cardiac activity.


A comparison of the release of a vasoactive-intestinal-peptide-like peptide and acetylcholine in the giant axon-Schwann cell preparation of the tropical squid Sepioteuthis sepioidea.
A vasoactive intestinal peptide (VIP)-like peptide is released by axonal stimulation in the giant axon-Schwann cell preparation from the tropical squid Sepioteuthis sepioidea. It is also released by direct application of l-glutamate, the giant axon-Schwann cell signalling molecule in this preparation. The release of the peptide parallels the release of acetylcholine from the Schwann cells themselves in this preparation in a number of different ways. The release of both acetylcholine and the VIP-like peptide have the same threshold (between 2x10(-10) and 5x10(-10 )mol l-1) for l-glutamate application and the same recovery time after inhibition of release by exposure of the preparation to a prolonged pulse of l-glutamate. A prolonged l-glutamate pulse of 10(-8 )mol l-1 releases both substances for as long as the pulse is applied to the preparation, whereas a prolonged pulse of 10(-9 )mol l-1 l-glutamate releases acetylcholine in the same way but releases the VIP-like peptide only transiently. The VIP-like peptide is likely to be co-released with acetylcholine from the Schwann cells.


Canine infectious tracheobronchitis: effects of an intranasal live canine parainfluenza-Bordetella bronchiseptica vaccine on viral shedding and clinical tracheobronchitis (kennel cough).
A modified-live intranasal (IN) canine parainfluenza (CPI)-virus Bordetella bronchiseptica vaccine was evaluated in dogs for efficacy against laboratory-induced canine infectious tracheobronchitis. The comparative efficacies of IN and parenteral administrations of the CPI virus fraction were also evaluated. The frequency and duration of clinical tracheobronchitis, blood serum agglutination titer, humoral antibody response, and duration of CPI virus and B bronchiseptica shedding were measured. Group A dogs were vaccinated subcutaneously or IM with an experimental CPI vaccine and challenge exposed with CPI virus. Group B dogs were vaccinated IN with avirulent CPI virus-B bronchiseptica live antigens and challenge exposed with virulent CPI virus and virulent B bronchiseptica. The IN vaccination (group B) significantly reduced (P less than or equal to 0.001) the occurrence of clinical tracheobronchitis by 96%. The combined challenge exposure of virulent CPI and virulent B bronchiseptica produced a synergistic enhancement of the clinical signs of kennel cough. The percentage of days after challenge exposure that virus shedding was detected for controls equaled 70% as compared with 50% and only 1% for parenterally and IN vaccinated dogs, respectively. Isolation of virulent B bronchiseptica microorganisms was reduced 89% in dogs vaccinated IN compared to controls. The geometric mean humoral antibody titers to CPI virus after 2 parenteral vaccinations and 1 IN vaccination were 1:43 and 1:34, respectively.


Activation of human blood platelets by arginine-vasopressin. Role of bivalent cations.
Arginine-vasopressin caused platelet activation, i.e., a shape change reaction and a rise in intracellular free Ca2+ ([Ca2+]i) only in the presence of certain bivalent cations. The EC50 of arginine-vasopressin (concentration causing half-maximal shape change) decreased with rising concentrations of Mn2+, Mg2+, or Ca2+ in the medium, but was at least an order higher with Ca2+ than with Mn2+ or Mg2+. The EC50 of the active bivalent cations (concentrations enabling 100 nM arginine-vasopressin to exert half-maximal shape change and rise in [Ca2+]i) varied with the individual cations, being by far the highest for Ca2+. The KD of [3H]arginine-vasopressin binding to platelet membranes and intact platelets markedly decreased when extracellular Mg2+ or Mn2+ were present, and the KD values were inversely related to the concentration of the cations. Ca2+ also lowered the KD values; however, the effect was less marked than that of Mg2+ or Mn2+ and, in physiological conditions, significant only in intact platelets. Vasopressin-1 antagonists counteracted arginine-vasopressin binding and the shape change reaction and [Ca2+]i rise induced by arginine-vasopressin. In the presence of Mn2+ in the medium, administration of arginine-vasopressin led to quenching of the intracellular fluorescence of 2-methyl-6-methoxy-8-nitroquinoline-loaded platelets, possibly due to influx of Mn2+. In conclusion, the dependency of the arginine-vasopressin-induced platelet activation on bivalent cations is at least partly due to an enhancement by these cations of the affinity of the vasopressin-1 receptor for arginine-vasopressin. Thereby, under physiological conditions, Mg2+ seems to be of primary importance. Other mechanisms may be involved, too, e.g., an enhancement by arginine-vasopressin of the influx of bivalent cations into the platelets.


Creutzfeldt-Jakob disease versus anti-LGI1 limbic encephalitis in a patient with progressive cognitive dysfunction, psychiatric symptoms, involuntary facio-brachio-crural movement, and an abnormal electroencephalogram: a case report.
Diagnosis of Creutzfeldt-Jakob disease (CJD) is often challenging in elderly individuals, not only because of its variable clinical features but also because of nonspecific changes on the electroencephalogram (EEG) in the early stages of the disease. Here we report on a patient who presented with progressive cognitive dysfunction, psychiatric symptoms, involuntary facio-brachio-crural movement, and an abnormal EEG. We provide a detailed analysis and differential diagnosis between anti-leucine-rich glioma inactivated 1 (LGI1) limbic encephalitis versus CJD, in the hope of providing a new understanding of CJD. A 65-year-old Chinese man presented with slowly progressive cognitive decline with psychiatric symptoms. On admission, he presented with facial grimacing and brief left upper limb dystonic posturing lasting 1-2 seconds, with hyponatremia that was difficult to rectify. Neurological examination showed increased muscle tension in the left limb but without pathological reflexes. His early EEG showed focal periodic wave complexes. Diffusion-weighted magnetic resonance imaging showed a suspected "lace sign" in the occipital cortex. His cerebrospinal fluid was negative for LGI1 antibodies and positive for 14-3-3 brain protein. Therefore, we made a presumptive diagnosis of CJD. At the following visit, a second EEG showed paroxysmal sharp wave complexes, but the patient had a poor prognosis. Atypical facio-brachio-crural movement and nonspecific EEG changes may occasionally be found in patients with CJD or anti-LGI1 encephalitis. Clinicians should not be dissuaded from a diagnosis of CJD where the EEG does not show paroxysmal sharp wave complexes in the early stages but abnormal facio-brachio-crural movement is present.


Cannabinoids, loratadine and allopurinol as novel additions to the antipsoriatic ammunition.
As the current antipsoriatic medications are commonly associated with deleterious side-effects, a determined search for safer agents, which could be used alone or in combination with current antipsoriatic drugs, would be very imperative. Psoriasis is believed to be characterized by a type 1 cytokine pattern; interferon-gamma, interleukin (IL)-2 and tumour necrosis factor (TNF)-alpha are predominantly expressed in this disorder. Nitric oxide, reactive oxygen species, histamine, leukotriene B4, and decreased [corrected] keratinocyte cyclic adenosine monophosphate/cyclic guanosine monophosphate (cAMP/cGMP) ratio are supposed to play roles in the pathogenesis of this disorder. Based on the immunopathogenesis of psoriasis, this paper introduces three novel, potential treatments for this clinical conundrum: (i) cannabinoids, which exert inhibitory effects on antigen processing and macrophage/T-cell interaction and also on the release of IL-2, TNF-alpha and nitric oxide from immune cells; (ii) loratadine, which is an antihistamine capable of increasing [corrected] the cAMP/cGMP ratio and the production of leukotriene B4; and (iii) allopurinol, which scavenges free radicals, inhibits the production of TNF-alpha, and downregulates the expression of intercellular adhesion molecule-1 and P2X7 receptors on monocytes/macrophages, which are involved in antigen presentation and production of the inflammatory response, respectively. Importantly, allopurinol, especially in combination with cyclosporin, has been shown to be effective against experimental autoimmune uveitis, which, like psoriasis, is a cell-mediated autoimmune disorder.


IPEM guidelines on dosimeter systems for use as transfer instruments between the UK primary dosimetry standards laboratory (NPL) and radiotherapy centres.
United Kingdom dosimetry codes of practice have traditionally specified one electrometer for use as a secondary standard, namely the Nuclear Enterprises (NE) 2560 NPL secondary standard therapy level exposure meter. The NE2560 will become obsolete in the foreseeable future. This report provides guidelines to assist physicists following the United Kingdom dosimetry codes of practice in the selection of an electrometer to replace the NE2560 when necessary. Using an internationally accepted standard (BS EN 60731:1997) as a basis, estimated error analyses demonstrate that the uncertainty (one standard deviation) in a charge measurement associated with the NE2560 alone is approximately 0.3% under specified conditions. Following a review of manufacturers' literature, it is considered that modern electrometers should be capable of equalling this performance. Additional constructural and operational requirements not specified in the international standard but considered essential in a modern electrometer to be used as a secondary standard are presented.


The effect of high-frequency jet ventilation on intracranial pressure in patients with closed head injuries.
Positive pressure ventilation (PPV) can increase intracranial pressure (ICP) in patients with closed head injuries. This adverse effect may be secondary to elevated peak airway pressures. High-frequency jet ventilation (HFJV) has been shown to produce lower peak airway pressures and decrease ICP in experimental animals. This report describes a patient with a head injury who was ventilated with a high-frequency jet ventilator.


Stable Isotope Analysis of Greenhouse Gases Requires Analyte Preconcentration.
Nitrous oxide (N2O) is an important trace gas contributing to global warming and depletion of ozone in the stratosphere. Its increasing abundance is caused mainly by anthropogenic sources, such as application of fertilizers in agriculture or emissions from industry. To understand the N2O global budget, its sources and sinks need to be well-described and quantified. In this project, a new method for N2O source appointment was developed that can help with this task. The method is based on analysis of the eight most abundant isotopic molecules of N2O, using quantum cascade laser absorption spectroscopy (QCLAS). The applicability of the method towards the N2O biogeochemical cycle was demonstrated on a prominent N2O source (bacterial denitrification) and the most important N2O sink (UV photolysis) on samples prepared in laboratory experiments. An extension of the QCLAS method to natural samples can be achieved by hyphenation with a preconcentration technique that increases concentration of the analyte and standardizes the sample matrix. This article provides an overview of currently applied preconcentration techniques in the field of greenhouse-gas analysis and a description of the preconcentration device TREX that will be employed in future projects with the developed QCLAS method.


The bidirectional interaction between the sympathetic nervous system and immune mechanisms in the pathogenesis of hypertension.
Over the last few years, evidence has accumulated to suggest that hypertension is, at least in part, an immune-mediated inflammatory disorder. Many links between immunity and hypertension have been established and provide a complex framework of mechanistic interactions contributing to the rise in BP. These include immune-mediated inflammatory processes affecting regulatory brain nuclei and interactions with other mediators of cardiovascular regulation such as the sympathetic nervous system. Sympathoexcitation differentially regulates T-cells based upon activation status of the immune cell as well as the resident organ. Exogenous and endogenous triggers activate signalling pathways in innate and adaptive immune cells resulting in pro-inflammatory cytokine production and activation of T-lymphocytes in the cardiovascular and renal regions, now considered major factors in the development of essential hypertension. The inflammatory cascade is sustained and exacerbated by the immune flow via the brain-bone marrow-spleen-gastrointestinal axis and thereby further aggravating immune-mediated pathways resulting in a vicious cycle of established hypertension and target organ damage. This review summarizes the evidence and recent advances in linking immune-mediated inflammation, sympathetic activation and their bidirectional interactions with the development of hypertension. LINKED ARTICLES: This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc.


New Delhi Metallo-β-Lactamase-Producing Enterobacterales Bacteria, Switzerland, 2019-2020.
Carbapenemase-producing Enterobacterales (CPE) bacteria are a critical global health concern; New Delhi metallo-β-lactamase (NDM) enzymes account for >25% of all CPE found in Switzerland. We characterized NDM-positive CPE submitted to the Swiss National Reference Center for Emerging Antibiotic Resistance during a 2-year period (January 2019-December 2020) phenotypically and by using whole-genome sequencing. Most isolates were either Klebsiella pneumoniae (59/141) or Escherichia coli (52/141), and >50% were obtained from screening swabs. Among the 108 sequenced isolates, NDM-1 was the most prevalent variant, occurring in 56 isolates, mostly K. pneumoniae (34/56); the next most prevalent was NDM-5, which occurred in 49 isolates, mostly E. coli (40/49). Fourteen isolates coproduced a second carbapenemase, predominantly an OXA-48-like enzyme, and almost one third of isolates produced a 16S rRNA methylase conferring panresistance to aminoglycosides. We identified successful plasmids and global lineages as major factors contributing to the increasing prevalence of NDMs in Switzerland.


CO2-limitation-inducible Green Recovery of fatty acids from cyanobacterial biomass.
Using genetically modified cyanobacterial strains, we engineered a Green Recovery strategy to convert membrane lipids into fatty acids for economical and environmentally sustainable biofuel production. The Green Recovery strategy utilizes lipolytic enzymes under the control of promoters induced by CO(2) limitation. Data indicate that strains of the cyanobacterium Synechocystis sp. PCC6803 engineered for Green Recovery underwent degradation of membrane diacylglycerols upon CO(2) limitation, leading to release of fatty acids into the culture medium. Recovered fatty acid yields of 36.1 × 10(-12) mg/cell were measured in one of the engineered strains (SD239). Green Recovery can be incorporated into previously constructed fatty-acid-secretion strains, enabling fatty acid recovery from the remaining cyanobacterial biomass that will be generated during fatty acid biofuel production in photobioreactors.


Anterior and Posterior Vertebral Column Resection Versus Posterior-only Technique: A Comparison of Clinical Outcomes and Complications in Congenital Kyphoscoliosis.
Retrospective cohort. The purpose of this study is to compare the anterior-posterior surgery to posterior-only vertebra resection for congenital kyphoscoliosis in pediatric patients. Vertebral column resection is a very powerful correction technique mainly used in the treatment of severe and rigid spinal deformities. The technique can be applied with combined anterior and posterior vertebral column resection (APVCR) or posterior-only vertebral column resection (PVCR) approaches. PVCR has gained popularity recently due to several apparent advantages, but APVCR is still believed by some to be a viable alternative, despite the use of an anterior exposure. A retrospective chart and radiographic review was performed including the patients with congenital kyphoscoliosis up to 16 years of age who were operated on by a single senior surgeon in our department after 2005. The data included surgical time, estimated blood loss, duration of hospital and postoperative intensive care unit stay, intraoperative and postoperative complications. Preoperative, postoperative, and follow-up radiographs were evaluated for scoliosis, kyphosis, and spinal balance. Twenty-six patients (20 girls, 6 boys) met the inclusion criteria. APVCR was performed on 17 (median age, 13.2 y) and PVCR on 9 (median age, 10.7 y). Scoliosis correction at the time of last follow-up was 54.3% and 52.6% for APVCR and PVCR, respectively, whereas the average kyphosis correction was 25.4 degrees in APVCR and 30.1 degrees in PVCR group. Surgical time, hospital stay, and estimated blood loss were all significantly higher in the APVCR group, whereas the complication rates were similar. No neurological or vascular complications were encountered. This study showed that although the operative time and surgical blood loss were higher with APVCR, there were no major complications and the radiologic outcomes were similar between APVCR and PVCR. APVCR should be considered as an acceptable technique especially in deformities where PVCR would be technically difficult or at the beginning of the spine surgeon's learning curve. Level III.


The transmission of the influenza virus from patient to emergency physician: No flu for you.
Significant morbidity and mortality is attributed to infection with the influenza virus annually and care is often sought in Emergency Departments (ED). The exposure of Emergency Department healthcare personnel and subsequent illness is speculated to be high but has not been quantified. All physicians and mid-level providers in a large tertiary care ED who cared for an Influenza-positive patient were identified and surveyed. Information was gathered regarding each provider's report of an Influenza-like illness during the study period as well as laboratory testing results, sick contacts and subsequent missed work. General descriptive information of Influenza-positive patients was extracted through a retrospective chart review. 1020 Influenza-positive patients were cared for by 106 physicians and advanced practice nurses. Patients testing positive for Influenza-A were more likely to be admitted (p = .003). The majority of patients (83%) were cared for by an attending only. Our provider survey response rate was 87%. 1 in 4 providers reported suffering from an Influenza-like illness during the study period and no providers subsequently missed work days. Only 4 (5%) of those providers sought medical care to receive testing. Overall, 2% of ED providers tested positive for Influenza. Among Emergency Department providers, transmission of clinically significant Influenza illness was low.


The effect of mesenchymal stem cells on chemotaxis of osteoclast precursor cells.
Regeneration of tissue, including bone, using mesenchymal stem cells (MSCs) has been progressing rapidly. Regeneration of bone requires the presence of an appropriate environment and efficient chemotaxis of cells to the target site. Differentiation of MSCs into mesenchymal cells has received considerable attention, but the effect of MSCs on chemotaxis is not well understood. In this study, we investigated the effect of MSCs on chemotaxis of RAW264 cells via C-C motif chemokine ligand 2 (CCL2). Balb/c mouse bone marrow-derived MSCs and RAW264 cells, which are osteoclast precursor cells, were co-cultured without cell contact. The gene expression of CCL2 in MSCs and CC-chemokine receptor 2 (CCR2) in RAW264 cells was determined using quantitative real-time PCR. Analysis of RAW264 cell chemotaxis was performed using the Boyden chamber assay. mRNAs for CCL2 and CCR2 were significantly upregulated upon co-culture in comparison to culture of either cell type alone, and the number of chemotactic RAW264 cells was significantly increased by co-culture. MSCs enhanced the chemotaxis of RAW264 cells, possibly via CCL2-CCR2 interaction, suggesting the potential utility of MSCs for tissue regeneration.


A reanalysis of protein polymorphism in Drosophila melanogaster, D. simulans, D. sechellia and D. mauritiana: effects of population size and selection.
Comparison of synonymous and nonsynonymous variation/substitution within and between species at individual genes has become a widely used general approach to detect the effect of selection versus drift. The sibling species group comprised of two cosmopolitan (Drosophila melanogaster and Drosophila simulans) and two island (Drosophila mauritiana and Drosophila sechellia) species has become a model system for such studies. In the present study we reanalyzed the pattern of protein variation in these species, and the results were compared against the patterns of nucleotide variation obtained from the literature, mostly available for melanogaster and simulans. We have mainly focused on the contrasting patterns of variation between the cosmopolitan pair. The results can be summarized as follows: (1) As expected the island species D. mauritiana and D. sechellia showed much less variation than the cosmopolitan species D. melanogaster and D. simulans. (2) The chromosome 2 showed significantly less variation than chromosome 3 and X in all four species which may indicate effects of past selective sweeps. (3) In contrast to its overall low variation, D. mauritiana showed highest variation for X-linked loci which may indicate introgression from its sibling, D. simulans. (4) An average population of D. simulans was as heterozygous as that of D. melanogaster (14.4% v.s. 13.9%) but the difference was large and significant when considering only polymorphic loci (37.2% v.s. 26.1%). (5) The species-wise pooled populations of these two species showed similar results (all loci = 18.3% v.s. 20.0%, polymorphic loci = 47.2% v.s. 37.6%). (6) An average population of D. simulans had more low-frequency alleles than D. melanogaster, and the D. simulans alleles were found widely distributed in all populations whereas the D. melanogaster alleles were limited to local populations. As a results of this, pooled populations of D. melanogaster showed more polymorphic loci than those of D. simulans (48.0% v.s. 32.0%) but the difference was reduced when the comparison was made on the basis of an average population (29.1% v.s. 21.4%). (7) While the allele frequency distributions within populations were nonsignificant in both D. melanogaster and D. simulans, melanogaster had fewer than simulans, but more than expected from the neutral theory, low frequency alleles. (8) Diallelic loci with the second allele with a frequency less than 20% had similar frequencies in all four species but those with the second allele with a frequency higher than 20% were limited to only melanogaster the latter group of loci have clinal (latitudinal) patterns of variation indicative of balancing selection. (9) The comparison of D. simulans/D. melanogaster protein variation gave a ratio of 1.04 for all loci and 1.42 for polymorphic loci, against a ratio of approximately 2-fold difference for silent nucleotide sites. This suggests that the species ratios of protein and silent nucleotide polymorphism are too close to call for selective difference between silent and allozyme variation in D. simulans. In conclusion, the contrasting levels of allozyme polymorphism, distribution of rare alleles, number of diallelic loci and the patterns of geographic differentiation between the two species suggest the role of natural selection in D. melanogaster, and of possibly ancient population structure and recent worldwide migration in D. simulans. Population size differences alone are insufficient as an explanation for the patterns of variation between these two species.


Artemisinin selectively decreases functional levels of estrogen receptor-alpha and ablates estrogen-induced proliferation in human breast cancer cells.
MCF7 cells are an estrogen-responsive human breast cancer cell line that expresses both estrogen receptor (ER) alpha and ERbeta. Treatment of MCF7 cells with artemisinin, an antimalarial phytochemical from the sweet wormwood plant, effectively blocked estrogen-stimulated cell cycle progression induced by either 17beta-estradiol (E(2)), an agonist for both ERs, or by propyl pyrazole triol (PPT), a selective ERalpha agonist. Artemisinin strongly downregulated ERalpha protein and transcripts without altering expression or activity of ERbeta. Transfection of MCF7 cells with ERalpha promoter-linked luciferase reporter plasmids revealed that the artemisinin downregulation of ERalpha promoter activity accounted for the loss of ERalpha expression. Artemisinin treatment ablated the estrogenic induction of endogenous progesterone receptor (PR) transcripts by either E(2) or PPT and inhibited the estrogenic stimulation of a luciferase reporter plasmid driven by consensus estrogen response elements (EREs). Chromatin immunoprecipitation assays revealed that artemisinin significantly downregulated the level of endogeneous ERalpha bound to the PR promoter, whereas the level of bound endogeneous ERbeta was not altered. Treatment of MCF7 cells with artemisinin and the pure antiestrogen fulvestrant resulted in a cooperative reduction of ERalpha protein levels and enhanced G(1) cell cycle arrest compared with the effects of either compound alone. Our results show that artemisinin switches proliferative human breast cancer cells from expressing a high ERalpha:ERbeta ratio to a condition in which ERbeta predominates, which parallels the physiological state linked to antiproliferative events in normal mammary epithelium.


Publishing, signaling, social capital, and gender: Determinants of becoming a tenured professor in German political science.
We apply event history analysis to analyze career and publication data of virtually all political scientists in German university departments, showing that each published refereed journal article increases a political scientist's chance for tenure by 9 percent, while other publications affect the odds for tenure only marginally and in some cases even negatively. Each received award and third party funding increases the odds for tenure by respectively 41 and 26 percent, while international experience, social capital and children hardly have a strong influence. Surprisingly, having degrees from a German university of excellence strongly decreases the odds for tenure. Women with similar credentials have at least 20 percent higher odds to get tenure than men. Our data therefore suggests that the lower factual hiring rates of women are better explained by a leaky pipeline, e.g. women leaving academia, rather than because women are not hired even when they are as productive as men. The article contributes to a better understanding of the role of meritocratic and non-meritocratic factors in achieving highly competitive job positions.


Left inguinal adenopathy two years after cytoreductive surgery: a rare sign of recurrence.
Ovarian cancer is the second most common gynecological cancer in the Western world. Despite a good response to treatment, most patients with ovarian cancer will relapse. The abdominal, pelvic, and retroperitoneal cavities represent the most common sites of ovarian cancer recurrence, with inguinal lymph node involvement rarely reported. Herein we report the case of a 48-year-old Caucasian female who underwent successful surgical and chemotherapy treatment for ovarian epithelial cancer. Two years later, the patient was found to have painless left inguinal adenopathy, which was subsequently found to be metastatic ovarian cancer. CA-125 levels were elevated despite the lack of any foci of metabolically active tissue on imaging. Inguinal lymph node involvement is a rare sign of ovarian cancer. Despite that, it is essential to consider ovarian cancer in the differential diagnosis for inguinal lymphadenopathy in a female patient.


How Much Will It Cost To Monitor Microbial Drinking Water Quality in Sub-Saharan Africa?
Microbial water quality monitoring is crucial for managing water resources and protecting public health. However, institutional testing activities in sub-Saharan Africa are currently limited. Because the economics of water quality testing are poorly understood, the extent to which cost may be a barrier to monitoring in different settings is unclear. This study used cost data from 18 African monitoring institutions (piped water suppliers and health surveillance agencies in six countries) and estimates of water supply type coverage from 15 countries to assess the annual financial requirements for microbial water testing at both national and regional levels, using World Health Organization recommendations for sampling frequency. We found that a microbial water quality test costs 21.0 ± 11.3 USD, on average, including consumables, equipment, labor, and logistics, which is higher than previously calculated. Our annual cost estimates for microbial monitoring of piped supplies and improved point sources ranged between 8 000 USD for Equatorial Guinea and 1.9 million USD for Ethiopia, depending primarily on the population served but also on the distribution of piped water system sizes. A comparison with current national water and sanitation budgets showed that the cost of implementing prescribed testing levels represents a relatively modest proportion of existing budgets (<2%). At the regional level, we estimated that monitoring the microbial quality of all improved water sources in sub-Saharan Africa would cost 16.0 million USD per year, which is minimal in comparison to the projected annual capital costs of achieving Sustainable Development Goal 6.1 of safe water for all (14.8 billion USD).


An MLL/COMPASS subunit functions in the C. elegans dosage compensation complex to target X chromosomes for transcriptional regulation of gene expression.
Here we analyze the essential process of X-chromosome dosage compensation (DC) to elucidate mechanisms that control the assembly, genome-wide binding, and function of gene regulatory complexes that act over large chromosomal territories. We demonstrate that a subunit of Caenorhabditis elegans MLL/COMPASS, a gene activation complex, acts within the DC complex (DCC), a condensin complex, to target the DCC to both X chromosomes of hermaphrodites for chromosome-wide reduction of gene expression. The DCC binds to two categories of sites on X: rex (recruitment element on X) sites that recruit the DCC in an autonomous, sequence-dependent manner, and dox (dependent on X) sites that reside primarily in promoters of expressed genes and bind the DCC robustly only when attached to X. We find that DC mutations that abolish rex site binding greatly reduce dox site binding but do not eliminate it. Instead, binding is diminished to the low level observed at autosomal sites in wild-type animals. Changes in DCC binding to these non-rex sites occur throughout development and correlate directly with transcriptional activity of adjacent genes. Moreover, autosomal DCC binding is enhanced by rex site binding in cis in X-autosome fusion chromosomes. Thus, dox and autosomal sites have similar binding potential but are distinguished by linkage to rex sites. We propose a model for DCC binding in which low-level DCC binding at dox sites is dictated by intrinsic properties correlated with high transcriptional activity. Sex-specific DCC recruitment to rex sites then enhances the magnitude of DCC binding to dox sites in cis, which lack high affinity for the DCC on their own. We also show that the DCC balances X-chromosome gene expression between sexes by controlling transcription.


Influence of secular trends and sample size on reference equations for lung function tests.
The aim of our study was to determine the contribution of secular trends and sample size to lung function reference equations, and establish the number of local subjects required to validate published reference values. 30 spirometry datasets collected between 1978 and 2009 provided data on healthy, white subjects: 19,291 males and 23,741 females aged 2.5-95 yrs. The best fit for forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and FEV(1)/FVC as functions of age, height and sex were derived from the entire dataset using GAMLSS. Mean z-scores were calculated for individual datasets to determine inter-centre differences. This was repeated by subdividing one large dataset (3,683 males and 4,759 females) into 36 smaller subsets (comprising 18-227 individuals) to preclude differences due to population/technique. No secular trends were observed and differences between datasets comprising >1,000 subjects were small (maximum difference in FEV(1) and FVC from overall mean: 0.30- -0.22 z-scores). Subdividing one large dataset into smaller subsets reproduced the above sample size-related differences and revealed that at least 150 males and 150 females would be necessary to validate reference values to avoid spurious differences due to sampling error. Use of local controls to validate reference equations will rarely be practical due to the numbers required. Reference equations derived from large or collated datasets are recommended.


Fmoc-Compatible and C-terminal-Sequence-Independent Peptide Alkyl Thioester Formation Using Cysteinylprolyl Imide.
We report an Fmoc-compatible and external-thiol-free method of peptide C-terminus thioesterification with cysteinylprolyl imide. The newly synthesized structure, i.e., cysteinylprolyl-thiazolidinone, provided high conversion and sequence-independent fast kinetics (90 min) in the diketopiperazine thioester formation under relatively mild conditions: pH 6.0, 37 °C. Employing this thioesterification method, we synthesized histone H3.2 bearing K56 acetylation.


Cause-specific mortality risks of anesthesiologists.
The health-related effects of the operating room environment are unclear. The authors compared mortality risks of anesthesiologists to those of internal medicine physicians between 1979 and 1995. The Physician Master File database, a listing of all US physicians, was used to identify anesthesiologists and general internists. The cohort of internists (n = 40,211) was a stratified random sample of all internists, frequency-matched to the cohort of anesthesiologists (n = 40,242) by gender, decade of birth, and US citizenship. The National Death Index was used to confirm death status and to determine specific causes of death. Mortality risks, adjusted for age, gender, and race, were compared using the Cox proportional hazards regression model. The standardized mortality ratios for all physicians were well below 1.0, except for suicide. The all-cause mortality ratios, and the risks of death caused by cancer and heart disease, did not differ between anesthesiologists and internists. Anesthesiologists had an increased risk of death from suicide (rate ratio [RR] = 1.45, 95% confidence interval [CI] = 1.07 - 1.97), drug-related death (RR = 2.79, 95% CI = 1.87 - 4.15), death from other external causes (RR = 1.53, 95% CI = 1.05 - 2.22), and death from cerebrovascular disease (RR = 1.39, 95% CI = 1.08 - 1.79). Male anesthesiologists had an increased risk of death from HIV (RR = 1.82, 95% CI = 1.09 - 3.02) and viral hepatitis (RR = 7.98, 95% CI = 1.0 - 63.84). Although the risk to anesthesiologists of drug-related deaths was highest in the first 5 years after medical school graduation, it remained increased over that of internists throughout the career. Substance abuse and suicide represent significant occupational hazards for anesthesiologists. New methods to combat substance abuse among anesthesiologists should be developed.


[Association of HLA antigens with thyrotoxic periodic paralysis].
Periodic paralysis is a rare and peculiar complication of thyrotoxicosis, especially in Chinese and Japanese patients. The susceptibility to autoimmune thyroid disease has recently been reported to be strongly linked with certain immunogenetic factors. The objective of this study was to seek a genetic marker by HLA typing in Chinese patients with thyrotoxic periodic paralysis (TPP). The distribution of HLA-A, B, C, DR and DQ antigens in 20 thyrotoxic patients with periodic paralysis and 51 thyrotoxic patients without periodic paralysis was compared with that in 100 controls. The results showed that among the patients with TPP, these was a highly significantly increase of HLA-B51 frequency and B51 appeared to be linked with Cw3 in a state of dysequilibrium.