Basal p38 mitogen-activated protein kinase regulates unliganded glucocorticoid receptor function in airway smooth muscle cells.
Like many steroid receptors, the glucocorticoid (GC) receptor (GR) is a phosphoprotein. Although there are multiple phosphorylation sites critical for GR transcriptional activity (i.e., serine [S]203, S211, and S226), their respective role in driving GR functions is highly cell specific. We have recently identified protein phosphatase 5 as an essential Ser/Thr phosphatase responsible for impairing GR function via S211 dephosphorylation in airway smooth muscle (ASM) cells. Because p38 mitogen-activated protein kinase (MAPK) directly phosphorylates GR in different cell types in a stimulus- and cell-dependent manner, we investigated the role of p38 MAPK on GR phosphorylation and function in ASM cells. Cells were transfected with 100 nM p38 MAPK small interfering RNA or 2 μg MAPK kinase 3 expression vector (a specific kinase that directly activates p38 MAPK) in the presence or absence of fluticasone (100 nM) and/or p38 MAPK pharmacological inhibitor SB203580. We found that p38 MAPK blockade positively regulates GR nuclear translocation and GR-dependent induction of the steroid-target gene GC-induced leucine zipper in a hormone-independent manner. We also found that p38 MAPK-dependent regulation of GR functions was associated with a differential action on GR phosphorylation at S203 and S211 residues. This study demonstrated that the inactive state of GR in resting conditions is not only ensured by the absence of the GC ligand but also by p38 MAPK-dependent phosphorylation of unliganded GR at specific residues, which appears to be important in determining the overall GC responsiveness of ASM cells.


Lipoprotein-associated oncornavirus-inactivating factor in the genus Mus: effects on murine leukemia viruses of laboratory and exotic mice.
High titers of oncornavirus-inactivating factor (OIF) were found previously in sera of laboratory mice. OIF is highly active against mouse xenotropic and polytropic envelope recombinant murine leukemia viruses (MuLVs) but not against ecotropic MuLVs. Of the 20 different mouse species or subspecies currently tested, that represent 4 subgenera, no OIF was found in the 3 subgenera more distant to the laboratory mouse. In the subgenus Mus, 7 of the 8 most distant species had no OIF, whereas all the ancestral species and subspecies of the laboratory mouse (Mus musculus musculus, Mus musculus domesticus), including a more distant member (Mus musculus cookii), had ample titers of OIF. A new separation technique was devised so that potential virus-neutralizing immunoglobulins could be separated by electrophoresis from OIF in small-volume serum samples. Active OIF was recovered from serum high-density lipoprotein, from very-low-density lipoprotein, as well as from chylomicron fractions. Murine sarcoma virus pseudotypes were made with several available exotic MuLV types. These pseudotype MuLVs were not susceptible to standard OIF preparations. The sera of exotic mice also had no factor analogous to OIF which would inactivate their own homologous or heterologous exotic MuLVs. It appears that, with one exception, OIF activity is limited to two subspecies of M. musculus and may be correlated in these subspecies with the presence of endogenous xenotropic MuLVs.


High osmol gap hyponatremia caused by icodextrin: A case series report.
Recently hyperosmolar hyponatremia following excessive off-label use of two exchanges of 2L icodextrin daily during peritoneal dialysis (PD) was reported. We encountered a cluster of three cases of PD patients who developed hyperosmolar hyponatremia during on-label use of icodextrin. This appeared to be due to absorption of icodextrin, since, after stopping icodextrin, the serum sodium level and osmol gap returned to normal, while a rechallenge again resulted in hyperosmolar hyponatremia. We excluded higher than usual concentrations of specific fractions of dextrins in fresh icodextrin dialysis fluid (lot numbers of used batches were checked by manufacturer). We speculate that in our patients either an exaggerated degradation of polysaccharide chains by α-amylase activity in dialysate, lymph and interstitium and/or rapid hydrolysis of the absorbed larger degradation products in the circulation may have contributed to the hyperosmolality observed, with the concentration of oligosaccharides exceeding the capacity of intracellular enzymes (in particular maltase) to metabolize these products to glucose. Both hyponatremia and hyperosmolality are risk factors for poor outcomes in PD patients. Less conventional PD prescriptions such as off-label use of two exchanges of 2L icodextrin might raise the risk of this threatening side effect. This brief report is intended to create awareness of a rare complication of on-label icodextrin use in a subset of PD patients and/or PD prescriptions.


Clinical characteristics and prognosis associated with multiple primary malignant tumors in non-Hodgkin lymphoma patients.
Patients with non-Hodgkin lymphoma (NHL) occasionally present with multiple primary malignant tumors (MPMTs). This study aimed to determine the clinical characteristics, survival, and risk factors of these patients. The median follow-up of 92 patients was 13.5 months (range 0.3-72). Overall, 21 patients had synchronous MPMTs and 71 had metachronous MPMTs. We classified patients in the latter group into metachronous first group (n=27) and metachronous second group (n=44). Diffuse large B-cell lymphoma was the most frequent histologic lymphoma type. The digestive system was the commonest site affected by the solid cancer. The 1- and 2-year survival rates were 86.5% and 70.5%, respectively. The overall survival (OS) rates were 67.9% and 36.2% at 2 and 3 years, respectively, in the metachronous first group; 73.8% and 73.8%, respectively, in the metachronous second group; and 68.1% and 56.7%, respectively, in the synchronous tumor group. There was no difference in the survival rate among the 3 groups before 2 years, but after 2 years, a shorter OS rate was observed in the metachronous first group than in the metachronous second group and synchronous tumor group. For all patients, age >60 years, male sex, and ⩾3 involved nodal sites were considered independent prognostic factors associated with survival. OS time was shorter in patients with NHL who developed a second tumor than in those who were diagnosed with solid cancer synchronously and second neoplasm after previous solid tumors. Long-term follow-up and effective treatment should be provided to these patients.


Three-dimensional quantitative structure-activity and structure-selectivity relationships of dihydrofolate reductase inhibitors.
Three-dimensional quantitative structure-activity relationship (3D-QSAR) modelling using comparative molecular similarity indices analysis (CoMSIA) was applied to a series of 406 structurally diverse dihydrofolate reductase (DHFR) inhibitors from Pneumocystis carinii (pc) and rat liver (rl). X-ray crystal structures of three inhibitors bound to pcDHFR were used for defining the alignment rule. For pcDHFR, a QSAR model containing 6 components was selected using leave-10%-out cross-validation (n= 240, q2 = 0.65), while a 4-component model was selected for rlDHFR (n= 237, q2 = 0.63); both include steric, electrostatic and hydrophobic contributions. The models were validated using a large test set, designed to maximise its diversity and to verify the predictive accuracy of models for extrapolation. The pcDHFR model has r2 = 0.60 and mean absolute error (MAE) = 0.57 for the test set after removing 4 outliers, and the rlDHFR model has r2 = 0.60 and MAE = 0.69 after removing 4 test set outliers. In addition, classification models predicting selectivity for pcDHFR over rlDHFR were developed using soft independent modelling by class analogy (SIMCA), with a selectivity ratio of 2 (IC50,rlDHFR/ IC50,pcDHFR) used for delimiting classes. A 5-component model including steric and electrostatic contributions has cross-validated and test set classification rates of 0.67 and 0.68 for selective inhibitors, and 0.85 and 0.72 for unselective inhibitors. The predictive accuracy of models, together with the identification of important contributions in QSAR and classification models, offer the possibility of designing potent selective inhibitors and estimating their activity prior to synthesis.


Cerebrospinal fluid rhinorrhoea and otorrhoea: extracranial repair.
Cerebrospinal fluid otorhinorrhoea is a well recognized problem. The otolaryngologist has a major role to play in the diagnosis and management of this condition. Five cases are described which illustrate the problems involved; four presented as leaks and one as pneumoencephalus and meningitis. Of the various methods of diagnosis and localization non-invasive techniques, i.e. tomography, CT and flexible endscopy are preferred. The extracranial extradural approach for anterior, middle and posterior fossa leaks allows a direct assault on the fistula. It may be usefully augmented by temporary lumbar drainage.


Enzymatic autoantibody glycan hydrolysis alleviates autoimmunity against type VII collagen.
Autoantibody-mediated diseases comprise a heterogeneous group of disorders in which the pathogenic potential of autoantibodies has been clearly demonstrated. In general, their treatment relies on the long-term use of systemic corticosteroids and other immunosuppressants that are associated with considerable adverse reactions. EndoS, an endoglycosidase derived from Streptococcus pyogenes, specifically hydrolyzes the N-linked glycan of native IgG and has previously been shown to modulate the interaction between the Fc portion of autoantibody and Fcγ receptors on leukocytes. Here, different models of autoimmunity to type VII collagen, a structural protein of the dermal-epidermal junction (DEJ), were employed to explore the therapeutic potential of EndoS. First, pretreatment of otherwise pathogenic anti-murine type VII collagen (mCOL7) IgG with EndoS significantly reduced split formation at the DEJ in cryosections of murine skin and abrogated clinical disease in mice. Next, the effect of EndoS was also seen when the enzyme was injected into mice after pathogenic anti-mCOL7 IgG had been administered. Finally, to mimic the patient situation even closer, EndoS was applied in mice that had already developed clinical disease after immunization with mCOL7. In all EndoS-treated mice, disease progression was stopped, and in the majority of mice, clinical disease even regressed. Of note, EndoS was shown to hydrolyze already in vivo-bound pathogenic autoantibodies. In addition, EndoS treatment decreased lesional expression of activating FcγRs while increasing FcγRIIB expression.


TCDD and cancer: a critical review of epidemiologic studies.
The authors reviewed the epidemiologic studies on exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and cancer risk, published since the last full-scale review made by the International Agency for Research on Cancer Monographs program in 1997. The update of a cohort of US herbicide producers generated negative results overall; the internal analysis provided evidence of an increased "all-cancer" risk in the highest exposure category, with a statistically significant exposure-response association in some of the many analyses performed. The update of a similar Dutch cohort did not confirm the previously observed association with TCDD exposure. The updated surveillance of the Seveso population provided evidence of increased all-cancer mortality 15-20 years after exposure among those living in the most contaminated area but might also reflect random variation, as overall excesses in the most recent follow-up were not observed. Corresponding data on cancer incidence offer little support to the mortality results. Updated results from cohort studies of Vietnam veterans potentially exposed to TCDD did not consistently suggest an increased risk of cancer. Results of additional, smaller studies of other occupational groups potentially exposed to TCDD, and of community-based case-control studies, did not provide consistent evidence of an increased cancer risk. In conclusion, recent epidemiological evidence falls far short of conclusively demonstrating a causal link between TCDD exposure and cancer risk in humans. The emphasis on results for overall cancer risk-rather than risk for specific neoplasms-is not justified on epidemiologic grounds and is not a reason for ignoring the weaknesses of the available evidence.


A psychometric assessment of a Swedish translation of Spreitzer's empowerment scale.
The psychometric properties of a Swedish translation of Spreitzer's (1995a) empowerment scale were assessed. Three parallel assessments were made of data from 1,107 female registered nurses, 758 female assistant nurses, and 107 male registered and assistant nurses. The analyses indicated that the psychometric properties of the scale can be considered satisfactory. Suggestions are made regarding future research in the fields of psychometrics and work- and health-psychology.


What drives interaction strengths in complex food webs? A test with feeding rates of a generalist stream predator.
Describing the mechanisms that drive variation in species interaction strengths is central to understanding, predicting, and managing community dynamics. Multiple factors have been linked to trophic interaction strength variation, including species densities, species traits, and abiotic factors. Yet most empirical tests of the relative roles of multiple mechanisms that drive variation have been limited to simplified experiments that may diverge from the dynamics of natural food webs. Here, we used a field-based observational approach to quantify the roles of prey density, predator density, predator-prey body-mass ratios, prey identity, and abiotic factors in driving variation in feeding rates of reticulate sculpin (Cottus perplexus). We combined data on over 6,000 predator-prey observations with prey identification time functions to estimate 289 prey-specific feeding rates at nine stream sites in Oregon. Feeding rates on 57 prey types showed an approximately log-normal distribution, with few strong and many weak interactions. Model selection indicated that prey density, followed by prey identity, were the two most important predictors of prey-specific sculpin feeding rates. Feeding rates showed a positive relationship with prey taxon densities that was inconsistent with predator saturation predicted by current functional response models. Feeding rates also exhibited four orders-of-magnitude in variation across prey taxonomic orders, with the lowest feeding rates observed on prey with significant anti-predator defenses. Body-mass ratios were the third most important predictor variable, showing a hump-shaped relationship with the highest feeding rates at intermediate ratios. Sculpin density was negatively correlated with feeding rates, consistent with the presence of intraspecific predator interference. Our results highlight how multiple co-occurring drivers shape trophic interactions in nature and underscore ways in which simplified experiments or reliance on scaling laws alone may lead to biased inferences about the structure and dynamics of species-rich food webs.


Tissue concentrations and pharmacokinetics of florfenicol in broiler chickens.
Florfenicol was once administered to broiler chickens via i.v., i.m. and oral route (30 mg/kg body weight) to study its plasma concentrations, kinetic behaviour, systemic bioavailability and tissue levels. Following a single i. v. injection, the kinetic disposition of florfenicol followed a two-compartmental open model with an elimination half-life of 172 min, total body clearance of 26.9 ml/kg/min and a steady state volume of distribution of 5.11 litre/kg. The highest plasma concentrations of florfenicol were 3.82 and 3.20 micrograms/ml following single i.m. and oral administration, respectively. The systemic bioavailability was 96.6 and 55.3 per cent after i.m. and oral administration. The plasma protein binding of florfenicol was 18.5%. Following the administration, the highest tissue concentration of the drug was found in kidney, bile, lung, muscle, intestine, heart, liver, spleen and serum. Low concentrations of the drug were found in brain, bone marrow and fat. No florfenicol residues were detected in tissues and serum after 72 h except in the bile, it disappeared after 96 h.


The problem of obesity: is there a role for antagonists of the renin-angiotensin system?
Obesity is a major health problem worldwide; it is associated with more than 30 medical conditions and is a leading cause of unnecessary deaths. Adipose tissue not only acts as an energy store, but also behaves like an endocrine organ, synthesising and secreting numerous hormones and cytokines. Angiotensin II (ANG II) is the biologically active component of the renin-angiotensin system (RAS). The RAS is present in adipose tissue and evidence suggests that ANG II is intimately linked to obesity. Indeed, ANG II increases fat cell growth and differentiation, increases synthesis, uptake and storage of fatty acids and triglycerides and possibly inhibits lipolysis. Evidence obtained using genetically modified animals has shown that the amount of body fat is directly related to the amount of ANG II, i.e., animals with low levels of ANG II have reduced fat stores while animals with excessive ANG II have increased fat stores. In humans, epidemiological evidence has shown that body fat is correlated with angiotensinogen, a precursor of ANG II, or other components of the RAS. Furthermore, blocking the production and/or actions of ANG II with drugs or natural substances decreases body fat. The decrease in body fat caused by such treatments predominantly occurs in abdominal fat depots and appears to be independent of energy intake and digestibility. Clearly, ANG II has an important role in the accumulation of body fat and the possibility exists that treatment of obesity will be enhanced by the use of natural or synthetic substances that interfere with ANG II.


Quantitative detection of Sphingomonas chlorophenolica in soil via competitive polymerase chain reaction.
The 16S ribosomal RNA gene sequence of the pentachlorophenol degrader Sphingomonas chlorophenolica strain RA2 was used to generate specific polymerase chain reaction (PCR) primers for the detection of this strain in soil, whereas a region internal to the two primers was used to provide an S. chlorophenolica strain RA2-specific oligonucleotide probe. The PCR detection system resulted in a 727 bp product detectable via gel electrophoresis and hybridization. It was specific for strain RA2 and its close relative, S. chlorophenolica ATCC 39723, as evidenced by PCR amplifications of a range of bacterial genomic DNAs. Tests of total microbial community DNA obtained from five uninoculated and two RA2-inoculated soils confirmed this specificity for introduced S. chlorophenolica RA2. Strain RA2 could be detected in soil down to a level of 10(3) cfu g-1 soil. Two strategies were followed to generate internal standard DNA for competitive PCR. First, a 479 bp MIMICS fragment was obtained based on a previously constructed gene cassette; however, this standard did not reliably quantify RA2 targets. Low stringency PCR performed with a range of bacterial genomic DNAs resulted in the generation of an amplicon with a Paenibacillus azotofixans strain that was slightly smaller than the RA2-derived product. Both products were easily separable via conventional gel electrophoresis. The use of this competitor in a threefold dilution scheme applied to the target DNA allowed for the quantitative detection of RA2-specific target DNA molecules from pure culture and from soil. The fate of strain RA2 in pentachlorophenol-contaminated soil was described using this competitive PCR approach, and the organism was shown to persist at two inoculum levels over prolonged periods of time.


Sensitive Next-Generation Sequencing Method Reveals Deep Genetic Diversity of HIV-1 in the Democratic Republic of the Congo.
As the epidemiological epicenter of the human immunodeficiency virus (HIV) pandemic, the Democratic Republic of the Congo (DRC) is a reservoir of circulating HIV strains exhibiting high levels of diversity and recombination. In this study, we characterized HIV specimens collected in two rural areas of the DRC between 2001 and 2003 to identify rare strains of HIV. The env gp41 region was sequenced and characterized for 172 HIV-positive specimens. The env sequences were predominantly subtype A (43.02%), but 7 other subtypes (33.14%), 20 circulating recombinant forms (CRFs; 11.63%), and 20 unclassified (11.63%) sequences were also found. Of the rare and unclassified subtypes, 18 specimens were selected for next-generation sequencing (NGS) by a modified HIV-switching mechanism at the 5' end of the RNA template (SMART) method to obtain full-genome sequences. NGS produced 14 new complete genomes, which included pure subtype C (n = 2), D (n = 1), F1 (n = 1), H (n = 3), and J (n = 1) genomes. The two subtype C genomes and one of the subtype H genomes branched basal to their respective subtype branches but had no evidence of recombination. The remaining 6 genomes were complex recombinants of 2 or more subtypes, including subtypes A1, F, G, H, J, and K and unclassified fragments, including one subtype CRF25 isolate, which branched basal to all CRF25 references. Notably, all recombinant subtype H fragments branched basal to the H clade. Spatial-geographical analysis indicated that the diverse sequences identified here did not expand globally. The full-genome and subgenomic sequences identified in our study population significantly increase the documented diversity of the strains involved in the continually evolving HIV-1 pandemic.IMPORTANCE Very little is known about the ancestral HIV-1 strains that founded the global pandemic, and very few complete genome sequences are available from patients in the Congo Basin, where HIV-1 expanded early in the global pandemic. By sequencing a subgenomic fragment of the HIV-1 envelope from study participants in the DRC, we identified rare variants for complete genome sequencing. The basal branching of some of the complete genome sequences that we recovered suggests that these strains are more closely related to ancestral HIV-1 strains than to previously reported strains and is evidence that the local diversification of HIV in the DRC continues to outpace the diversity of global strains decades after the emergence of the pandemic.


The analysis of QT interval and repolarization morphology of the heart in chronic exposure to lead.
There are no common recommendations regarding electrocardiographic monitoring in occupationally exposed workers. Therefore, the present study was designed to investigate whether exposure to lead results in an increase of selected electrocardiography (ECG) pathologies, such as QT interval prolongation and repolarization disorders, in occupationally exposed workers. The study group included 180 workers occupationally exposed to lead compounds. The exposed group was divided according to the median of the mean blood lead level (PbBmean) calculated based on a series of measurements performed during 5-year observation period (35 µg/dl) into two subgroups: low exposure (LE, PbBmean = 20.0-35.0 µg/dl) and high exposure (HE, PbBmean = 35.1-46.4 µg/dl). The control group consisted of 69 healthy workers without occupational exposure to lead. ECG evaluation included the analysis of heart rate (HR), QT interval and repolarization abnormalities. Mean QT interval was significantly greater in the exposed population than in the control group by 2%. In the HE group, mean QT interval was significantly greater than in the control group by 4% and significantly different from those noted in the LE group. Positive correlations between QT interval and lead exposure indices were also reported. Besides, there was a negative correlation between HR and blood lead level. Increased concentration of lead in the blood above 35 μg/dl is associated with the QT interval prolongation, which may trigger arrhythmias when combined with other abnormalities, such as long QT syndrome. Therefore, electrocardiographic evaluation should be a part of a routine monitoring of occupationally exposed populations.


Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: a multicentre study.
Vaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity and safety of messenger RNA (mRNA) vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited. A multicentre observational study evaluated the immunogenicity and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD (n=686) compared with the general population (n=121). Serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured 2-6 weeks after the second vaccine dose. Seropositivity was defined as IgG ≥15 binding antibody units (BAU)/mL. Vaccination efficacy, safety, and disease activity were assessed within 6 weeks after the second vaccine dose. Following vaccination, the seropositivity rate and S1/S2 IgG levels were significantly lower among patients with AIIRD versus controls (86% (n=590) vs 100%, p<0.0001 and 132.9±91.7 vs 218.6±82.06 BAU/mL, p<0.0001, respectively). Risk factors for reduced immunogenicity included older age and treatment with glucocorticoids, rituximab, mycophenolate mofetil (MMF), and abatacept. Rituximab was the main cause of a seronegative response (39% seropositivity). There were no postvaccination symptomatic cases of COVID-19 among patients with AIIRD and one mild case in the control group. Major adverse events in patients with AIIRD included death (n=2) several weeks after the second vaccine dose, non-disseminated herpes zoster (n=6), uveitis (n=2), and pericarditis (n=1). Postvaccination disease activity remained stable in the majority of patients. mRNA BNTb262 vaccine was immunogenic in the majority of patients with AIIRD, with an acceptable safety profile. Treatment with glucocorticoids, rituximab, MMF, and abatacept was associated with a significantly reduced BNT162b2-induced immunogenicity.


Disrupting the clustering of GABAA receptor α2 subunits in the frontal cortex leads to reduced γ-power and cognitive deficits.
In schizophrenia, cognitive dysfunction is highly predictive of poor patient outcomes and is not responsive to current medications. Postmortem studies have suggested that cognitive deficits in schizophrenia are correlated with modifications in the number and size of inhibitory synapses. To test if these modifications lead to cognitive deficits, we have created a dominant-negative virus [adeno-associated (AAV)-DN1] that disrupts the clustering of γ-aminobutyric acid type A receptors (GABA(A)Rs) at postsynaptic inhibitory specializations. When injected into the frontal cortex of mice, AAV-DN1 impairs GABA(A)R α2 subunit and GABA transporter 1 (GAT-1) clustering, but increases GABA(A)R α1 subunit clustering on the perisomatic region, with no influence on axon-initial segment clustering. Mice expressing AAV-DN1 have prepulse inhibition deficits and impairments in working memory. Significantly, these behavioral deficits are paralleled by a reduction in electroencephalography γ-power. Collectively, our study provides functional evidence revealing that GABAergic synapses in the prefrontal cortex directly contribute to cognition and γ-power.


Effect of Dexmedetomidine Added to Modified Pectoral Block on Postoperative Pain and Stress Response in Patient Undergoing Modified Radical Mastectomy.
The most common surgical procedure for breast cancer is the modified radical mastectomy (MRM), but it is associated with significant postoperative pain. Regional anesthesia can reduce the stress response associated with surgical trauma. Our aim is to explore the efficacy of 1 µg/kg dexmedetomedine added to an ultrasound (US)-modified pectoral (Pecs) block on postoperative pain and stress response in patients undergoing MRM. A randomized, double-blind, prospective study. An academic medical center. Sixty patients with American Society of Anesthesiologists (ASA) physical status I-II (18-60 years old and weighing 50-90 kg) scheduled for MRM were enrolled and randomly assigned into 2 groups (30 in each) to receive a preoperative US Pecs block with 30 mL of 0.25% bupivacaine only (group 1, bupivacaine group [GB]) or 30 mL of 0.25% bupivacaine plus 1 µg/kg dexmedetomidine (group II, dexmedetomidine group [GD]). The patients were followed-up 48 hours postoperatively for vital signs (heart rate [HR], noninvasive blood pressure [NIBP], respiratory rate [RR], and oxygen saturation [Sao2]), visual analog scale (VAS) scores, time to first request of rescue analgesia, total morphine consumption, and side effects. Serum levels of cortisol and prolactin were assessed at baseline and at 1 and 24 hours postoperatively. A significant reduction in the intraoperative HR, systolic blood pressure (SBP), and diastolic blood pressure (DBP) starting at 30 minutes until 120 minutes in the GD group compared to the GB group (P < 0.05) was observed. The VAS scores showed a statistically significant reduction in the GD group compared to the GB group, which started immediately up until 12 hours postoperatively (P < 0.05). There was a delayed time to first request of analgesia in the GD group (25.4 ± 16.4 hrs) compared to the GB group (17 ± 12 hrs) (P = 0.029), and there was a significant decrease of the total amount of morphine consumption in the GD group (9 + 3.6 mg) compared to the GB group (12 + 3.6 mg) (P = 0.001). There was a significant reduction in the mean serum cortisol and prolactin levels at 1 and 24 hours postoperative in the GD patients compared to the GB patients (P < 0.05). This study was limited by its sample size. The addition of 1 µg/kg dexmedetomidine to an US-modified Pecs block has superior analgesia and more attenuation to stress hormone levels without serious side effects, compared to a regular Pecs block in patients who underwent MRM. Postoperative pain, dexmedetomidine, Pecs block, stress response, breast surgery.


Brain systems underlying attentional control and emotional distraction during working memory encoding.
Goal-directed behavior requires that cognitive operations can be protected from emotional distraction induced by task-irrelevant emotional stimuli. The brain processes involved in attending to relevant information while filtering out irrelevant information are still largely unknown. To investigate the neural and behavioral underpinnings of attending to task-relevant emotional stimuli while ignoring irrelevant stimuli, we used fMRI to assess brain responses during attentional instructed encoding within an emotional working memory (WM) paradigm. We showed that instructed attention to emotion during WM encoding resulted in enhanced performance, by means of increased memory performance and reduced reaction time, compared to passive viewing. A similar performance benefit was also demonstrated for recognition memory performance, although for positive pictures only. Functional MRI data revealed a network of regions involved in directed attention to emotional information for both positive and negative pictures that included medial and lateral prefrontal cortices, fusiform gyrus, insula, the parahippocampal gyrus, and the amygdala. Moreover, we demonstrate that regions in the striatum, and regions associated with the default-mode network were differentially activated for emotional distraction compared to neutral distraction. Activation in a sub-set of these regions was related to individual differences in WM and recognition memory performance, thus likely contributing to performing the task at an optimal level. The present results provide initial insights into the behavioral and neural consequences of instructed attention and emotional distraction during WM encoding.


Levothyroxine use and the risk of colorectal cancer: a large population-based case-control study.
Whether an association between oral levothyroxine use, leading to supraphysiological exposure of the colon to thyroid hormones, and risk of colorectal cancer exists in humans is unclear. We therefore aimed to assess whether the use of levothyroxine is associated with a reduced risk of colorectal cancer in a linked cohort of pharmacy and cancer data. Population-based matched case-control study. A total of 28,121 patients diagnosed with colorectal cancer between 1998 and 2014 were matched to 106,086 controls. Multivariable logistic regression was used to estimate the association between levothyroxine use and occurrence of colorectal cancer, adjusted for potential confounders. Results were stratified by gender, age, tumour subtype, and staging, as well as treatment duration and dosing. A total of 1066 colorectal cancer patients (4%) and 4024 (4%) controls had used levothyroxine at any point before index date (adjusted odds ratio 0.95 (0.88-1.01)). Long-term use of levothyroxine was seen in 323 (30%) colorectal cancer patients and 1111 (28%) controls (adjusted odds ratio 1.00 (0.88-1.13)). Stratification by tumour subsite showed a borderline significant risk reduction of rectal cancer, while this was not seen for proximal colon cancer or distal colon cancer. There was no relationship with treatment duration or with levothyroxine dose. In this study, no reduced risk of colorectal cancer was seen in levothyroxine users. When stratifying by tumour subsite, a borderline significant risk reduction of rectal cancer was found and may warrant further research.


Duration of tick attachment as a predictor of the risk of Lyme disease in an area in which Lyme disease is endemic.
Animal studies have shown an exponential increase in the risk of Borrelia burgdorferi infection after 48-72 h of deer tick attachment. Persons with tick bites were prospectively studied to determine if those with prolonged tick attachment constitute a high-risk group for infection. Ticks were identified, measured for engorgement, and assayed by polymerase chain reaction (PCR) for B. burgdorferi DNA. Duration of attachment was determined from the scutal index of engorgement. Of 316 submissions, 229 were deer ticks; 14% were positive by PCR. Paired sera and an intact tick for determination of duration of attachment were available for 105 subjects (109 bites). There were 4 human cases (3.7% of bites) of B. burgdorferi infection. The incidence was significantly higher for duration of attachment > or =72 h than for <72 h: 3 (20%) of 15 vs. 1 (1.1%) of 94 (P = .008; odds ratio, 23.3; 95% confidence interval, 2.2-242). PCR was an unreliable predictor of infection. Tick identification and measurement of engorgement can be used to identify a small, high-risk subset of persons who may benefit from antibiotic prophylaxis.


Nursing students' self-determination: the influence on stigmatizing attitude within clinical placement settings.
The training of future health professionals is a complex and dynamic endeavour, whereby students engage in a variety of experiences and learning activities. Skills developed through classes are applied and further developed within authentic settings, such as clinical placements. While there is a wealth of literature that has examined the influence of clinical placements, less inquiry has examined whether the personal traits and/or characteristics of students play a role in their professional learning and development. Specifically, a key trait that has been viewed as influencing the education and growth of people, yet has received little focus in the nursing literature, is self-determination. Therefore, the purpose of this study was to examine whether students' self-determination influences their level of professional learning, as measured by their stigmatizing attitudes, within a clinical placement. Participants were undergraduate nursing students classified as either high or low in their self-determination and engaged in a compulsory 80-hour mental health clinical placement. Data were collected using a battery of surveys to assess their self-determination towards their work and stigmatizing attitude towards people with mental illness. Using a two-group pre test and post test design, statistical analysis revealed a significant difference whereby students with high self-determination towards work possessed less stigmatizing attitudes after completing their clinical placement. Results from this study provide empirical evidence that personality elements such as self-determination and motivation towards work can play a role in the education of future professionals.


Solvothermal synthesis of organoclay/Cu-MOF composite and its application in film modified GCE for simultaneous electrochemical detection of deoxyepinephrine, acetaminophen and tyrosine.
An organoclay/copper-based metal-organic framework (MOF) composite was synthesized using a solvothermal method by growing a Cu-BTC (copper(ii) benzene-1,3,5-tricarboxylate) MOF from a mixture of the MOF precursor solution in which various amounts of organoclay had been dispersed. The organoclay was obtained by intercalating a cationic dye, namely thionin, into a natural Cameroonian clay sampled in Sagba deposit (North West of Cameroon). The organoclay and the as-synthesized composites were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and Brunauer, Emmett and Teller (BET) techniques. From Scherrer's equation, the crystallite size of the composite was found to be between 55 and 58 nm, twice as large as the pristine MOF's crystallite size. The organoclay/Cu-MOF composite (Sa-TN50/Cu3(BTC)2) exhibiting a BET surface area of 192 m2 g-1, about twice that of pristine clay and about one seventh that of pristine MOF, was then utilized to form a stable thin film onto glassy carbon electrodes (GCE) by drop coating (Sa-TN50/Cu3(BTC)2/GCE). These electrodes demonstrated electrocatalytic behavior toward deoxyepinephrine (DXEP) and thus enabled selective and simultaneous sensitive detection of three analytes: DXEP, acetaminophen (AC) and tyrosine (TYR) compared with bare GCE and clay modified electrode. Under optimum conditions, Sa-TN50/Cu3(BTC)2/GCE exhibited good performance including large calibration curves ranging from 5.0 μM to 138.0 μM for DXEP, 4.0 μM to 153.0 μM for AC and 1.0 μM to 29.4 μM for TYR. The detection limits were found to be, 0.4 μM, 0.7 μM and 0.2 μM for DXEP, AC and TYR, respectively. The developed sensors have been applied successfully in the quantification of AC in a commercial tablet of AC, and DXEP, AC and TYR in tap water.


Monounsaturated fats from plant and animal sources in relation to risk of coronary heart disease among US men and women.
Monounsaturated fatty acids (MUFAs) improve blood lipid profiles in intervention studies, but prospective evidence with regard to MUFA intake and coronary heart disease (CHD) risk is limited and controversial. We investigated the associations of cis MUFA intake from plant (MUFA-P) and animal (MUFA-A) sources with CHD risk separately among 63,442 women from the Nurses' Health Study (1990-2012) and 29,942 men from the Health Professionals Follow-Up Study (1990-2012). Intakes of MUFA-Ps and MUFA-As were calculated by using validated food-frequency questionnaires collected every 4 y. Incident nonfatal myocardial infarction and fatal CHD cases (n = 4419) were confirmed by medical record review. During follow-up, MUFA-Ps and MUFA-As contributed 5.8-7.9% and 4.2-5.4% of energy on average, respectively. When MUFA-Ps were modeled to isocalorically replace other macronutrients, HRs (95% CIs) of CHD were 0.83 (0.68, 1.00) for saturated fatty acids (SFAs; 5% of energy), 0.86 (0.76, 0.97) for refined carbohydrates (5% of energy), and 0.80 (0.70, 0.91) for trans fats (2% of energy) (P = 0.05, 0.01, and 0.001, respectively). For MUFA-As, corresponding HRs (95% CIs) for the same isocaloric substitutions were 1.04 (0.79, 1.38) for SFAs, 1.11 (0.91, 1.35) for refined carbohydrates, and 0.88 (0.77, 1.01) for trans fats (P = 0.76, 0.31, and 0.08, respectively). Given the common food sources of SFAs and MUFA-As (Spearman correlation coefficients of 0.81-0.83 between these groups of fatty acids), we further estimated CHD risk when the sum of MUFA-As and SFAs (5% of energy) was replaced by MUFA-Ps, and found that the HR was 0.81 (95% CI: 0.73, 0.90; P < 0.001) for this replacement. The largely different associations of MUFA-Ps and MUFA-As with CHD risk suggest that plant-based foods are the preferable sources of MUFAs for CHD prevention. These findings are observational and warrant confirmation in intervention settings. This study was registered at clinicaltrials.gov as NCT00005152 and NCT00005182.


The Meaning of Emoji to Describe Food Experiences in Pre-Adolescents.
Ongoing research has shown that emoji can be used by children to discriminate food products, but it is unclear if they express emotions and how they are linked to emotional words. Little is known about how children interpret emoji in terms of their emotional meaning in the context of food. This study aimed at investigating the emotional meaning of emoji used to describe food experiences in 9-13-year-old pre-adolescents and to measure related age and gender differences. The meaning of 46 emoji used to describe food experience was explored by: mapping emoji according to similarities and differences in their emotional meaning using the projective mapping technique, and linking emoji with emotion words using a check-all-that-apply (CATA) format. The two tasks gave consistent results and showed that emoji were discriminated along the valence (positive vs. negative) and power (dominant vs. submissive) dimension, and to a lower extent along the arousal dimension (high vs. low activation). In general, negative emoji had more distinct meanings than positive emoji in both studies, but differences in nuances of meaning were found also among positive emoji. Girls and older pre-adolescents (12-13 years old (y.o.)) discriminated positive emoji slightly better than boys and younger pre-adolescents (9-11 y.o.). This suggests that girls and older pre-adolescents may be higher in emotional granularity (the ability to experience and discriminate emotions), particularly of positive emotions. The results of the present work can be used for the development of an emoji-based tool to measure emotions elicited by foods in pre-adolescents.


Interferon treatment of multiple pulmonary malignancies associated with papilloma virus.
Over a period of four years, beginning in spring 1988, a previously healthy man developed a primary squamous cell carcinoma of the tonsil, treated with radiotherapy, followed by 10 distinct, primary bronchial squamous cell carcinomas. Four of the cancers were surgically resected, all of which were positive by hybridization for human papilloma virus (type 16). Following the institution of alpha interferon, three smaller lesions disappeared and a larger one shrank in size, facilitating surgical resection. Over the following seven years no new ones have appeared. The finding of papilloma virus in malignancies should prompt consideration of antiviral therapy.


Noninvasive assessment of liver fibrosis in patients with chronic hepatitis B.
Infection with hepatitis B virus is an important health problem worldwide: it affects more than 350 million people and is a leading cause of liver-related morbidity, accounting for 1 million deaths annually. Hepatic fibrosis is a consequence of the accumulation of extracellular matrix components in the liver. An accurate diagnosis of liver fibrosis is essential for the management of chronic liver disease. Liver biopsy has been considered the gold standard for diagnosing disease, grading necroinflammatory activity, and staging fibrosis. However, liver biopsy is unsuitable for repeated evaluations because it is invasive and can cause major complications, including death. Several noninvasive evaluations have been introduced for the assessment of liver fibrosis: serum biomarkers, combined indices or scores, and imaging techniques including transient elastography, acoustic radiation force impulse, real-time tissue elastography, and magnetic resonance elastography. Here, we review the recent progress of noninvasive assessment of liver fibrosis in patients with chronic hepatitis B. Most noninvasive evaluations for liver fibrosis have been validated first in patients with chronic hepatitis C, and later in those with chronic hepatitis B. The establishment of a noninvasive assessment of liver fibrosis is urgently needed to aid in the management of this leading cause of chronic liver disease.


Effect of single-drug therapy on reduction of left ventricular mass in mild to moderate hypertension: comparison of six antihypertensive agents. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.
Antihypertensive drugs may differ in their ability to reduce LV mass. Covariates other than drug selection, such as pretreatment LV mass, body weight, the magnitude of blood pressure reduction, race, and age may modify the response of LV mass to therapy. Patients with mild to moderate hypertension (diastolic blood pressure, 95 to 109 mm Hg) were randomly allocated to treatment with atenolol, captopril, clonidine, diltiazem, hydrochlorothiazide, or prazosin in a double-masked trial. Patients achieving the goal diastolic blood pressure of <90 mm Hg during drug titration entered a 1-year maintenance period. Longitudinal analysis examined changes from baseline echocardiogram in LV mass at 8 weeks and at 1 year, statistically adjusted for pretreatment LV mass, systolic blood pressure, body weight, sodium excretion, physical activity, race, and age. Significant reductions at 1 year in adjusted LV mass were seen for patients in the highest tertile of pretreatment LV mass treated with hydrochlorothiazide (mean, -42.9; 95% confidence limits, -65.5, -20.2 g), captopril (mean, -38.7; 95% confidence limits, -61.0, -16.4 g), and atenolol (mean, -28.1; 95% confidence limits, -50.9, -5.3 g). These treatment effects differed from those of prazosin, diltiazem, or clonidine. Antihypertensive drugs have disparate effects on LV mass independent of the magnitude of blood pressure reduction. Patients with adequate blood pressure control on captopril, hydrochlorothiazide, and atenolol show a reduction of LV mass after 1 year of treatment, whereas patients on diltiazem, clonidine, or prazosin do not.


The anti-tumor effect of taxifolin on lung cancer via suppressing stemness and epithelial-mesenchymal transition in vitro and oncogenesis in nude mice.
Taxifolin is a natural flavonoid with anti-oxidant and anti-proliferative properties. In this study, we investigated the stemness-related inhibitory effects of taxifolin in two lung cancer cell lines, A549 and H1975, as well as in A549 xenografts. A549 and H1975 cells, as well as A549 xenograft BALB/c mice were treated with taxifolin. Cell viability, stemness, mobility and protein expression were tested with Cell counting kit-8 (CCK-8), Colony formation assay, Flow cytometry, Transwell, Western blot and Immunohistochemistry, respectively. CCK-8 exhibited an obvious toxicity of taxifolin to both cell lines at higher dose. Then taxifolin of 0, 25, 50, and 100 µM/L were subsequently used. Taxifolin exhibited inhibitory effects on stemness and sphere formation, reduced protein expression of SOX2 and OCT4, and reduced CD133-positive cells. Furthermore, taxifolin decreased invasive cells, reduced N-cadherin and vimentin while increased E-cadherin expression, indicating that epithelial-mesenchymal transition (EMT) was inhibited. All of the effects observed were exhibited in a dose-dependent manner, and A549 cells proved to be more sensitive to taxifolin than H1975 cells. Taxifolin inactivated PI3K and TCF4 protein phosphorylation; however, taxifolin was not observed to have an effect on NF-κB P65 or STAT3. Taxifolin also suppressed tumor growth in A549 xenograft BALB/c mice, with decreased SOX2 and OCT4 expression and inhibited PI3K and TCF4. In summary, taxifolin inhibited stemness and EMT in lung cancer cells possibly via the inactivation of PI3K and OCT4. Taxifolin could be a potential prodrug or serve as an adjuvant in lung cancer treatment.


The Salivary Microbiome and Predicted Metabolite Production are Associated with Progression from Barrett's Esophagus to Esophageal Adenocarcinoma.
Esophageal adenocarcinoma (EAC) is rising in incidence and associated with poor survival, and established risk factors do not explain this trend. Microbiome alterations have been associated with progression from the precursor Barrett's esophagus (BE) to EAC, yet the oral microbiome, tightly linked to the esophageal microbiome and easier to sample, has not been extensively studied in this context. We aimed to assess the relationship between the salivary microbiome and neoplastic progression in BE to identify microbiome-related factors that may drive EAC development. We collected clinical data and oral health and hygiene history and characterized the salivary microbiome from 250 patients with and without BE, including 78 with advanced neoplasia (high grade dysplasia or early adenocarcinoma). We assessed differential relative abundance of taxa by 16S rRNA gene sequencing and associations between microbiome composition and clinical features and used microbiome metabolic modeling to predict metabolite production. We found significant shifts and increased dysbiosis associated with progression to advanced neoplasia, with these associations occurring independent of tooth loss, and the largest shifts were with the genus Streptococcus. Microbiome metabolic models predicted significant shifts in the metabolic capacities of the salivary microbiome in patients with advanced neoplasia, including increases in L-lactic acid and decreases in butyric acid and L-tryptophan production. Our results suggest both a mechanistic and predictive role for the oral microbiome in esophageal adenocarcinoma. Further work is warranted to identify the biological significance of these alterations, to validate metabolic shifts, and to determine whether they represent viable therapeutic targets for prevention of progression in BE.


The Importance of Defining the Coronary Anatomy in Suspected Myopericarditis: A Case Report.
BACKGROUND It is challenging to distinguish between acute coronary syndrome (ACS) and myocardial injury due to alternative causes (eg myopericarditis, coronary vasospasm, and pulmonary embolism), as they often share similar presentations, especially in young patients. Coronary computerized tomography angiography (CCTA) is increasingly recognized as a fast and safe diagnostic tool for rapid assessment of the coronary anatomy among patients with a low to intermediate cardiovascular risk profile and/or atypical chest pain. However, its utility among patients with possible ACS is still debated. CASE REPORT A 36-year-old man presented to our institution with intermittent pleuritic chest pain and malaise over the preceding 7 days. He was a smoker and his father had ACS at the age of 45 years. The patient had unspecific electrocardiographic changes and elevated troponin values. The initial transthoracic echocardiogram indicated a normal ejection fraction without any wall motion abnormalities. Presuming a very low chance of coronary artery disease due to his age and atypical symptoms, we ordered a CCTA, which identified a thrombotic lesion in the right coronary artery (RCA). An invasive coronary angiography, including an optical coherence tomography, confirmed the presence of a thrombotic lesion located at the level of the proximal RCA, which was consequently treated with 1 drug-eluting stent. CONCLUSIONS Physicians should always eliminate underlying coronary artery disease among patients with unclear myocardial injury, irrespective of a patient's presentation, age, and estimated cardiovascular risk. In this context, CCTA represents a safe and simple tool to rapidly assess the coronary anatomy, especially in younger patients.


Characterization of Listeria monocytogenes isolates in import food products of China from 8 provinces between 2005 and 2007.
A total of 48 Listeria monocytogenes isolates of different import food products from 8 provinces between 2005 and 2008 were characterized. The serotype and virulence were confirmed for each strain and molecular subtyping were analyzed by multilocus sequence typing (MLST). Twenty five strains were assigned to serotype 1/2a, and 11 isolates to serotype 1/2b, serotype 4b were found in 7 isolate, and the remaining 5 strains were grouped into serotypes 1/2c, 4a, and 4e. Molecular subtyping schemes found thirty two sequence types (STs) among these isolates and the majority of L. monocytogenes strains belonged to lineage II (56%), followed by lineage I (38%), lineage III (6%). Two molecular subtype clusters, cluster A included all isolates of lineage II, while cluster B contained the isolates of lineages I and lineages III. Two L. monocytogenes strains were not grouped in either of the two clusters. Fifty three isolates were as virulent as L. monocytogenes reference strain EGD in mouse virulence assay, while the isolates 22213 and 22265 had low pathogenicity. These results provide the first molecular insight into the L. monocytogenes strains isolated from import food products of 8 provinces in China and indicate the potential risk to cause human disease if intake by contaminated foods. MLST could be used as a routine subtyping method of L. monocytogenes isolates. In China, inspection and quarantine strategies of imported foods should be strengthened. There is a potential risk of listeriosis in China and routine subtyping of L. monocytogenes isolates is important. It is necessary for food hygiene management to strengthen the supervision of imported foods.


Predictors of self-reported health-related quality of life according to the EQ-5D-Y in chronically ill children and adolescents with asthma, diabetes, and juvenile arthritis: longitudinal results.
Health-related quality of life (HRQoL) is an important patient-reported outcome in clinical and health research. The EQ-5D-Y assesses child and adolescent HRQoL by five items on mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as a visual analogue scale (VAS) on the current health state. This study investigates predictors of self-reported HRQoL according to the EQ-5D-Y in chronically ill children and adolescents using longitudinal data. Data from the German Kids-CAT study on children and adolescents with asthma, diabetes, and juvenile arthritis gathered over a period of six months were analyzed (n = 310; 7-17 years old; 48% female). Self-, parent-, and pediatrician-reported data were collected from June 2013 to October 2014. Generalized linear mixed models and linear mixed models served to examine effects of socio-demographic as well as disease- and health-specific predictors on the items as well as on the VAS of the EQ-5D-Y. Ceiling effects for the EQ-5D-Y indicated low burden of disease in the analyzed sample. Longitudinal analyses revealed associations between less health complaints and better HRQoL for all investigated HRQoL domains. Further, age- and gender-specific effects, and associations of better disease control, longer duration of the disease and less mental health problems with better HRQoL were found. Subjective health complaints and mental health problems should be considered in the care of children and adolescents with asthma, diabetes, and juvenile arthritis. Future research should suggest administering the items of the EQ-5D-Y with five instead of three response options, and investigate HRQoL over a longer period.


[Magnetic resonance in malformations of the central nervous system].
Comments are made over a number of patients with malformations of the central nervous system, who have undergone magnetic resonance studies. Descriptions are made of the anatomic findings and their characteristics, and emphasis is given to the advantage magnetic resonance studies offer in patients with brain malformations.


[The status of the pituitary-gonadal system and immunologic parameters in patients with rheumatoid arthritis].
Male and female patients suffering from rheumatoid arthritis demonstrated disorders in the pituitary-gonadal system, which manifested in the body estrogenization in the presence of androgenic deficiency. The correlations between the levels of estradiol, testosterone and the parameters of the cellular and humoral immunity were analyzed. The authors discuss the problem of the participation of the disorders in the pituitary-gonadal system in the development of an autoimmune process underlying rheumatoid arthritis.


MicroRNA-deficient Schwann cells display congenital hypomyelination.
MicroRNAs, by modulating gene expression, have been implicated as regulators of various cellular and physiological processes, including differentiation, proliferation, and cancer. Here, we study the role of microRNAs in Schwann cell (SC) differentiation by conditional removal of the microRNA processing enzyme Dicer1. We reveal that both male and female mice lacking Dicer1 in SC (Dicer1 conditional knock-outs) display a severe neurological phenotype resembling congenital hypomyelination. Ultrastructural analyses show that many SC lacking Dicer1 are stalled in differentiation at the promyelinating state and fail to myelinate axons. Gene expression analyses reveal a failure to extinguish genes characteristic of the undifferentiated state such as Sox2, Jun, and Ccnd1. Sox2 and Jun are well characterized negative regulators of SC differentiation. Consistent with Sox2/Jun maintenance, Egr2, a master regulator of the myelinating program, is drastically downregulated and likely accounts for the myelination defect. We posit a model wherein microRNAs are critical for downregulation of antecedent programs of gene expression. In SC differentiation, this is particularly relevant in the key developmental transition from a promyelinating to myelinating SC.


Partial forced expiratory flow-volume curves in young children during ketamine anesthesia.
Maximal flows at functional residual capacity (VmaxFRC) from partial forced expiratory flow-volume (PEFV) curves were obtained in 14 normal preschool children (8 boys, 6 girls) of average age 44 mo, under general anesthesia before elective surgery. PEFV curves were generated from end inspiration by rapid compression of the chest wall with an inflatable jacket. VmaxFRC, expressed in milliliter per second, correlated linearly with height, weight, age, and FRC in milliliter and milliliters per kilogram. The best correlation of VmaxFRC (ml/s) was to height to the power of 2.47, which agrees with the results predicted by wave-speed theory. Mean FRC-corrected VmaxFRC was 2.42 +/- 0.50 (SD) FRC's/s with no significant difference between boys (2.35 FRC's/s) and girls (2.51 FRC's/s). There was no correlation between lung-size corrected VmaxFRC and height, weight, or age, but it tended to decrease with increasing FRC. The intersubject variability for VmaxFRC was reduced by normalizing for FRC, and was significantly better than that reported for awake children. This can be attributed to the greater control over volume history and more reliable maximal flow generation during anesthesia. The intrasubject coefficient of variation (CV) for VmaxFRC was 12.2%, and the intersubject CV was 20.0%. The difference may represent the variability due to dysanapsis. It is concluded that dysanapsis is not a prominent factor in children of this age group. In addition, the similarity of the regression equation for VmaxFRC vs. height to that of FRC vs. height supports the concept of equidimensional growth of the airways and lung parenchyma.


Effects of light intervention on alertness and mental performance during the post-lunch dip: a multi-measure study.
Disrupting sleepiness and fatigue during the post-lunch dip by environmental factors may result in a decrease in human errors and accidents, and enhance job performance. Recent studies have shown that both red white light as well as blue white light can have a positive effect on human alertness and mental functioning. In the present study, the light intervention was evaluated for its effectiveness on alleviating the post-lunch dip. Twenty healthy volunteers experienced 117 min of four light conditions preceded by a 13-min initial dim light while performing a continuous performance test (CPT) and undergoing recording of the electroencephalogram (EEG): blue-enriched white light (12,000 K, 500 lx, BWL), red saturated white light (2,700 K, 500 lx, RWL), normal white light (4,000 K, 500 lx, NWL), and dim light (<5 lx, DL) conditions. Other outcome measures were subjective sleepiness, mood, and performance tests (working memory, divided attention, and inhibitory capacity). We found that exposure to both BWL and RWL conditions decreased the lower alpha-band power compared to the NWL and DL conditions. No significant differences were observed in subjective sleepiness and mental performance during sustained attention, working memory, and inhibitory capacity tasks between NWL, RWL, and BWL conditions. The present findings suggest that both RWL and BWL, compared to NWL condition, can improve the physiological correlates of alertness in EEG measurements. However, these changes did not translate to improvements in task performance and subjective alertness.


New housing conditions: improving the welfare of experimental animals.
As animal experiments and testing are still a necessary part of the discovery and development of new drugs and do not seem likely to be totally replaced in the foreseeable future, it is important that the care and use of these animals are continuously refined. Since the housing facilities are where most experimental animals spend the major part of their lives, this area should be given special attention to ensure optimal welfare for the animals. In a unique collaboration between a pharmaceutical company and an animal welfare organisation, the housing conditions of mice, rats, guinea-pigs, rabbits and dogs, respectively, were reviewed with focus on the basic needs of the animals. Prototypes for new housing systems satisfying the most important of these basic needs of the animals were developed, with valuable input from international experts with special knowledge of the behaviour of experimental animals. These new housing systems and species-specific, newly introduced socialisation programmes contribute to improved animal welfare and a better occupational health of the animal caretakers. Since these new housing systems are more pleasant and appealing, they may also have the added benefit that they contribute to a broader public acceptance of the use of experimental animals.


Detection of circulating tumor cells in patients with breast cancer using the quantitative RT-PCR assay for monitoring of therapy efficacy.
Circulating tumor cells (CTCs) are an independent prognostic factor for patients with breast cancer. However, the role of CTCs in early breast cancer management is not yet clearly defined. The aim of this study was to isolate and characterize CTCs in blood sample of a breast cancer patient as a biomarker for monitoring treatments efficacy. In this study, 692 blood samples from 221 breast cancer patients and 376 healthy individuals was used to detect CTCs with multiple markers including epithelial cell adhesion molecule (EpCAM), cytokeratin (CK) 19, human epidermal growth factor (HER) 2, Ki67, human telomerase reverse transcriptase (hTERT), and vimentin using quantitative reverse transcription PCR (RT-qPCR). A total of 153 (69.2%) blood samples of 221 patients with breast cancer were found to be positive for at least one of the cancer-associated marker gene before treatment. After chemotherapy, no CTCs were found in 28 (33.3%) of the 84 blood samples analyzed for the presence of CTCs using the RT-qPCR, whereas 56 (66.7%) blood samples were still found to be positive for at least one of the markers. After completing the therapy, the CTC positivity rate decreased to 7 (20.6%) in the neoadjuvant group, whereas this increased to 7 (14%) cases in the adjuvant group. There was no statistically significant relationship between TNM stage and detection of CTC-related markers. Data from this study suggest that RT-qPCR assay for the detection of CTC markers might be useful in selecting appropriate therapeutics and for monitoring treatment efficacy in breast cancer patients.


Contemporary perspectives on the use of radiation therapy for locally advanced gallbladder cancer.
Locally advanced gallbladder cancer poor prognosis due to a high distant metastatic rate and poor overall disease control. The impact of standard therapeutic options is unfortunately modest. Due to the rarity of the disease, evidence-based management continues to evolve. The goal of this review is to highlight the contemporary landscape of radiation therapy for gallbladder cancer. First, the rationale for radiation therapy is described. This includes the risk of locoregional recurrence following resection based on patterns-of-failure data, along with the high locoregional disease burden being a frequent cause morbidity and mortality in unresected cases. Additionally, improvements in systemic therapy over the next decade could shift contemporary patterns of failure more towards proportionally higher locoregional recurrence rates. Second, clinical data of radiation therapy for gallbladder cancer are discussed. These include consideration of postoperative chemoradiotherapy for margin- and/or node-positive cases. Patients with localized unresectable disease could benefit from ablative radiation therapy, based on promising data in non-gallbladder cancer pancreaticobiliary neoplasms. The use of advanced radiation therapy technologies such as proton beam therapy, as a means to deliver ablative radiation therapy in a potentially safer manner, is also mentioned. Lastly, the emerging concept of neoadjuvant therapy for gallbladder cancer is also described, in efforts to allow more patients to receive curative resection.


The Effects of Oral Isotretinoin in Women with Acne and Polycystic Ovary Syndrome.
Many patients who were diagnosed as polycystic ovary syndrome- (PCOS-) related acne were not capable of sustaining or beginning oral contraceptive pills (OCPs) due to pill scaring, contraindications of OCP use, migraine, or smoking. In this situation, oral isotretinoin treatment may become an important option for PCOS-related acne. The aim of the study was to determine the effects of isotretinoin treatment on PCOS patients who were complicated with severe cystic acne. This study consisted of 40 female patients diagnosed as PCOS complicated with severe cystic acne. These patients were not eligible candidates for OCP use due to migraine, thrombophilia, heavy smoking, or pill scare. To establish baseline values of hormone levels, on days 2-5 of the menstrual cycle, venous blood samples were obtained. Moreover Modified Ferriman-Gallwey (mFG) score, acne score (AS), follicle count, and bilateral ovarian volumes were evaluated both before and after isotretinoin treatment. Isotretinoin treatment significantly decreased Ferriman-Gallwey score, free testosterone, insulin level, hemoglobin level, acne score, and ovarian volume. Increased triglyceride and cholesterol levels were detected after treatment. Isotretinoin treatment may have beneficial effects on free testosterone, insulin, acne score, and Ferriman-Gallwey score. Solely isotretinoin administration may supply adequate healing in PCOS patients' symptoms complicated with severe cystic acne who is not eligible candidates for OCP use. This trial is registered with Clinicaltrials.gov NCT02855138.


The facilitating role of dispositional mindfulness in the process of posttraumatic growth: A prospective investigation.
Traumatic events can lead not only to psychological distress but also to posttraumatic growth (PTG). As trauma challenge one's fundamental assumptions, traumatized individuals may initially experience intrusive rumination. However, these challenged assumptions could facilitate further cognitive processing of trauma (i.e., deliberate rumination), which in turn fosters PTG. Adaptive cognitive processes, such as reduced rumination, have been linked to dispositional mindfulness. Thus, the current study aimed to investigate the potential role of dispositional mindfulness in the process of PTG. A 3-wave longitudinal design was employed to capture temporal changes in PTG. At the initial assessment (time 1), 259 traumatized individuals were assessed with regard to their trauma experiences, core belief challenge, intrusive and deliberate rumination, posttraumatic stress symptoms (PTSS), PTG, and dispositional mindfulness. The surveys were repeated after 1 month (time 2) and 7 months (time 3). Over time, the first indirect association of core belief challenge was increased PTG through recent intrusive and deliberate rumination, and the second indirect association of core belief challenge was decreased PTG through recent intrusive rumination and PTSS. In addition, dispositional mindfulness significantly moderated these 2 indirect associations. Individuals with a medium level of mindfulness at time 1 had lower levels of rumination and PTSS at time 3 compared to individuals with a low level of mindfulness. In the face of trauma, dispositional mindfulness promotes resilience through a subsequent reduction in rumination and PTSS. Our results highlight the protective role of dispositional mindfulness in long-term outcomes of trauma exposure. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Fluorescence microscopy: established and emerging methods, experimental strategies, and applications in immunology.
Cutting-edge biophysical technologies including total internal reflection fluorescence microscopy, single molecule fluorescence, single channel opening events, fluorescence resonance energy transfer, high-speed exposures, two-photon imaging, fluorescence lifetime imaging, and other tools are becoming increasingly important in immunology as they link molecular events to cellular physiology, a key goal of modern immunology. The primary concern in all forms of microscopy is the generation of contrast; for fluorescence microscopy contrast can be thought of as the difference in intensity between the cell and background, the signal-to-noise ratio. High information-content images can be formed by enhancing the signal, suppressing the noise, or both. As improved tools, such as ICCD and EMCCD cameras, become available for fluorescence imaging in molecular and cellular immunology, it is important to optimize other aspects of the imaging system. Numerous practical strategies to enhance fluorescence microscopy experiments are reviewed. The use of instrumentation such as light traps, cameras, objectives, improved fluorescent labels, and image filtration routines applicable to low light level experiments are discussed. New methodologies providing resolution well beyond that given by the Rayleigh criterion are outlined. Ongoing and future developments in fluorescence microscopy instrumentation and technique are reviewed. This review is intended to address situations where the signal is weak, which is important for emerging techniques stressing super-resolution or live cell dynamics, but is less important for conventional applications such as indirect immunofluorescence. This review provides a broad integrative discussion of fluorescence microscopy with selected applications in immunology.


Placental vascularization and apoptosis in Type-1 and gestational DM.
The objective of this study is to analyze the alteration in vascularization and apoptosis in the placentas of patients with Type 1 or gestational diabetes mellitus. Placental samples drawn from normal (n = 6), GDM (n = 6), and Type 1 DM (n = 6) pregnancies were rinsed in PBS and fixed in 4% paraformaldehyde. The obtained sections were examined by both light and electron microscopy. Subsequently, immunohistochemical staining was performed to evaluate apoptosis and vascularization with caspase-9 and VEGF antibodies. Capillary structures in various sizes, both in free and in stem villi, were observed to be denser in the GDM group than in the control and Type-1 DM groups, utilizing electron microscopy. Similarly, when compared with Type-1 DM and controls, a decreased amount of microvilli with more irregularity and blunting on the villus surface was detected. GDM group showed increased immunoreactivity in capillaries of stem villi, free villi, and endothelial cells when compared with Type-1 DM and control groups. Regarding the immunohistochemical staining with VEGF, Type-1 DM, and GDM groups showed stronger immunoreactivity than the control group, especially in syncytiotrophoblastic cell nuclei and stromal cell nuclei. However, there was no significant difference between Type-1 DM and GDM groups. Type-1 DM and GDM placentas showed increased villous stromal capillarization, increased immunoreactivity with VEGF and caspase-9, and increased syncytial nodes, which may develop secondary to placental hypoxia-ischemia. However, more participants are needed to confirm these conclusions.


Antigenic variation among members of the tick-borne encephalitis complex.
The antigenic relationships between seven members of the tick-borne encephalitis complex of flaviviruses (group B arboviruses) were examined by raising a library of 16 monoclonal antibodies against one of them and examining their biological and antigenic properties. These clones reacted with only one of two intracellular, virus-specific polypeptides. One polypeptide [mol. wt. 58 X 10(3) (58K)] is related to the major envelope protein E, but the identity of the other is at present unknown, even though it is a major immunogen in experimental infections and vaccinations. Only those clones specific for the 58K polypeptide contain either neutralizing or haemagglutinin-inhibiting activity, but these epitopes are not identical. In general, epitopes on the 51K polypeptide were more heavily conserved than those on the 58K polypeptide, although both conserved and variant epitopes were found on both polypeptides. One epitope was present on the 51K polypeptide which was conserved on all seven isolates studied and another epitope on the same polypeptide was specific for all the western isolates including one isolate of louping-ill virus. Using the monoclonal antibodies raised in the study, it was shown that louping-ill virus was closely related antigenically to isolates of the Western subtype of tick-borne encephalitis virus.


A threshold longitudinal Tobit quantile regression model for identification of treatment-sensitive subgroups based on interval-bounded longitudinal measurements and a continuous covariate.
Identification of a subgroup of patients who may be sensitive to a specific treatment is an important problem in precision medicine. This article considers the case where the treatment effect is assessed by longitudinal measurements, such as quality of life scores assessed over the duration of a clinical trial, and the subset is determined by a continuous baseline covariate, such as age and expression level of a biomarker. Recently, a linear mixed threshold regression model has been proposed but it assumes the longitudinal measurements are normally distributed. In many applications, longitudinal measurements, such as quality of life data obtained from answers to questions on a Likert scale, may be restricted in a fixed interval because of the floor and ceiling effects and, therefore, may be skewed. In this article, a threshold longitudinal Tobit quantile regression model is proposed and a computational approach based on alternating direction method of multipliers algorithm is developed for the estimation of parameters in the model. In addition, a random weighting method is employed to estimate the variances of the parameter estimators. The proposed procedures are evaluated through simulation studies and applications to the data from clinical trials.


Do agricultural grasses bred for improved root systems provide resilience to machinery-derived soil compaction?
The increasing frequency of droughts and floods on grasslands, due to climate change, increases the risk of soil compaction. Soil compaction affects both soil and forage productivity. Differing grasses may counteract some effects of compaction due to differences in their root architecture and ontogeny. To compare their resilience to soil compaction, three Festulolium (ryegrass and fescue species' hybrids) forage grass cultivars comprising differing root architecture and ontogeny were compared in replicated field plots, together with a ryegrass and tall fescue variety as controls. Pre-compaction soil and forage properties were determined in spring using > four-year-old plots to generate baseline data. Half of each field plot was then artificially compacted using farm machinery. Forage dry matter yield (DMY) was determined over four cuts. After the final harvest, post compaction soil characteristics and root biomass (RB) were compared between grasses in the non-compacted and compacted soils. Pre-compaction data showed that soil under Festulolium and ryegrass had similar water infiltration rates, higher than soil under tall fescue plots. Tiller density of the Festulolium at this time was significantly higher than fescue but not the ryegrass control. Forage DMY was significantly lower (p < .001) with compacted soil at the first cut but, by the completion of the growing season, there was no effect of soil compaction on total DMY. Tall fescue had a higher total DMY than other grasses, which all produced similar annual yields. Soil bulk density and penetration resistance were higher, and grass tiller density was lower in compacted soils. Root biomass in compacted soils showed a tendency for Festulolium cv Lp × Fg to have higher RB than the ryegrass at 0-15 cm depth. Overall, findings showed alternative grass root structures provide differing resilience to machinery compaction, and root biomass production can be encouraged without negative impacts on forage productivity.


Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase.
The medicinal properties of marijuana have been recognized for centuries, but clinical and societal acceptance of this drug of abuse as a potential therapeutic agent remains fiercely debated. An attractive alternative to marijuana-based therapeutics would be to target the molecular pathways that mediate the effects of this drug. To date, these neural signaling pathways have been shown to comprise a cannabinoid receptor (CB(1)) that binds the active constituent of marijuana, tetrahydrocannabinol (THC), and a postulated endogenous CB(1) ligand anandamide. Although anandamide binds and activates the CB(1) receptor in vitro, this compound induces only weak and transient cannabinoid behavioral effects in vivo, possibly a result of its rapid catabolism. Here we show that mice lacking the enzyme fatty acid amide hydrolase (FAAH(-/-)) are severely impaired in their ability to degrade anandamide and when treated with this compound, exhibit an array of intense CB(1)-dependent behavioral responses, including hypomotility, analgesia, catalepsy, and hypothermia. FAAH(-/-)-mice possess 15-fold augmented endogenous brain levels of anandamide and display reduced pain sensation that is reversed by the CB(1) antagonist SR141716A. Collectively, these results indicate that FAAH is a key regulator of anandamide signaling in vivo, setting an endogenous cannabinoid tone that modulates pain perception. FAAH may therefore represent an attractive pharmaceutical target for the treatment of pain and neuropsychiatric disorders.


Late reactivation of hepatitis B virus after rituximab-containing chemotherapy for mantle cell lymphoma: a case report.
Hepatitis B virus (HBV) reactivation is commonly observed in HBsAg-positive hematologic patients undergoing immunosuppressive chemotherapy. Recent guidelines recommend antiviral prophylaxis to be continued for up to 12 months after the discontinuation of the anticancer regimen. We report a case of a patient who underwent antiviral prophylaxis for 26 months after the discontinuation of a rituximab-containing chemotherapy regimen for a lymphoma and was admitted in the infectious diseases department with a 3-day history of jaundice, itching, and dark urine. After excluding other possible causes of acute liver damage, HBV reactivation was suspected. HBV-DNA was 4497000 IU/mL. Following reintroduction of entecavir, we observed a steady decline of ALT, AST, bilirubin and HBV-DNA serum levels, with a rapid resolution of acute hepatitis and an improvement in clinical conditions; one year after the event of HBV reactivation and beginning of antiviral therapy, the patient was virologically suppressed. Our study demonstrates that the risk of HBV reactivation in HBsAg-positive patients with undetectable HBV-DNA can occur even after three years from the last administration of rituximab and several months after the withdrawal of prophylactic antiviral therapy in patients with hematological malignancies. This implies that a close monitoring of HBV-related markers including HBV-DNA must continue after the withdrawal of prophylactic NA therapy.


[The role of therapeutic education in the treatment of atopic dermatitis in children].
Atopic dermatitis (AD) is a chronic disease of the skin that has heavy impact on the quality of life of children affected and raises the question of compliance, which frequently leads to treatment failure. Various problems are at the origin of poor compliance, such as the progressive loss of parents' motivation, the complexity of treatments, the corticosteroid phobia of health care workers and patients, and the side effects induced by treatment, their inefficiency and their cost. Therapeutic training is aimed at helping the patients to cope with their disease and to avoid the related complications. Its aim is to permit patients, and those who surround them, to acquire competence and sufficient knowledge so as to become autonomous. This acquisition and appropriation of competence by the patients requires personalised surveillance. Hence, therapeutic education is a continuous process of accompanying the patient throughout training. It is not a substitute to treatment but is conducted in parallel, to enable the patients to optimize their quality of life. Therapeutic training is already recognised as a crucial element in the management of many diseases. Despite the difficulties encountered, educational centres would clearly improve the management of AD.


Calcitriol, parathyroid hormone, and accumulation of aluminum in bone in dogs with renal failure.
Accumulation of aluminum in bone is a frequent finding in patients requiring chronic dialysis and is associated with considerable morbidity and/or mortality. Until now, evidence seemed to point to relatively low circulating levels of parathyroid hormone as a contributing factor, but because levels of parathyroid hormone and calcitriol are interrelated, calcitriol might be also involved. In this study we employed an animal model to evaluate the single and combined effects of parathyroid hormone and calcitriol on bone aluminum accumulation. The results show significantly less aluminum accumulation in calcitriol-replete dogs independent of the presence or absence of parathyroid hormone. These results indicate that low levels of calcitriol may play a role in the development of aluminum related bone disease. Further studies are needed to demonstrate whether administration of calcitriol in patients with renal insufficiency will prevent development of aluminum-related bone disease.


Evaluation of levodopa and carbidopa antioxidant activity in normal human lymphocytes in vitro: implication for oxidative stress in Parkinson's disease.
The main pathochemical hallmark of Parkinson's disease (PD) is the loss of dopamine in the striatum of the brain, and the oral administration of levodopa (L-dopa) is a treatment that partially restores the dopaminergic transmission. In vitro assays have demonstrated both toxic and protective effects of L-dopa on dopaminergic cells, while in vivo studies have not provided any convincing data. The peripheral metabolic pathways significantly decrease the amount of L-dopa reaching the brain; therefore, all of the current commercial formulations require an association with an inhibitor of dopa-decarboxylase, such as carbidopa. However, the dosage and the actual effectiveness of carbidopa have not yet been well defined. PD patients exhibit a reduced efficiency of the endogenous antioxidant system, and peripheral blood lymphocytes (PBLs) represent a dopaminergic system for use as a cellular model to study the pharmacological treatments of neurodegenerative disorders in addition to analysing the systemic oxidative stress. According to our previous studies demonstrating a protective effect of both L-dopa and carbidopa on neuroblastoma cells in vitro, we used the PBLs of healthy donors to evaluate the modulation of DNA damage by different concentrations of L-dopa and carbidopa in the presence of oxidative stress that was exogenously induced by H2O2. We utilised a TAS assay to evaluate the in vitro direct scavenging activity of L-dopa and carbidopa and analysed the expression of genes that were involved in cellular oxidative metabolism. Our data demonstrate the antioxidant capacity of L-dopa and carbidopa and their ability to protect DNA against oxidative-induced damage that derives from different mechanisms of action.


Understanding food security issues in remote Western Australian Indigenous communities.
Food insecurity in remote Western Australian (WA) Indigenous communities. This study explored remote community store managers' views on issues related to improving food security in order to inform health policy. A census of all remote WA Indigenous community store managers was conducted in 2010. Telephone interviews sought managers' perceptions of community food insecurity, problems with their store, and potential policy options for improving the supply, accessibility, affordability and consumption of nutritious foods. Descriptive analyses were conducted using SPSS for Windows version 17.0. Managers stated that freight costs and irregular deliveries contributed to high prices and a limited range of foods. Poor store infrastructure, compromised cold chain logistics, and commonly occurring power outages affected food quality. Half of the managers said there was hunger in their community because people did not have enough money to buy food. The role of nutritionists beyond a clinical and educational role was not understood. Food security interventions in remote communities need to take into consideration issues such as freight costs, transport and low demand for nutritious foods. Store managers provide important local knowledge regarding the development and implementation of food security interventions. SO WHAT? Agencies acting to address the issue of food insecurity in remote WA Indigenous communities should heed the advice of community store managers that high food prices, poor quality and limited availability are mainly due to transport inefficiencies and freight costs. Improving healthy food affordability in communities where high unemployment and low household income abound is fundamental to improving food security, yet presents a significant challenge.


Tales from the future-nuclear cardio-oncology, from prediction to diagnosis and monitoring.
Cancer and cardiovascular diseases (CVD) often share common risk factors, and patients with CVD who develop cancer are at high risk of experiencing major adverse cardiovascular events. Additionally, cancer treatment can induce short- and long-term adverse cardiovascular events. Given the improvement in oncological patients' prognosis, the burden in this vulnerable population is slowly shifting towards increased cardiovascular mortality. Consequently, the field of cardio-oncology is steadily expanding, prompting the need for new markers to stratify and monitor the cardiovascular risk in oncological patients before, during, and after the completion of treatment. Advanced non-invasive cardiac imaging has raised great interest in the early detection of CVD and cardiotoxicity in oncological patients. Nuclear medicine has long been a pivotal exam to robustly assess and monitor the cardiac function of patients undergoing potentially cardiotoxic chemotherapies. In addition, recent radiotracers have shown great interest in the early detection of cancer-treatment-related cardiotoxicity. In this review, we summarize the current and emerging nuclear cardiology tools that can help identify cardiotoxicity and assess the cardiovascular risk in patients undergoing cancer treatments and discuss the specific role of nuclear cardiology alongside other non-invasive imaging techniques.


Carotenoid silk coloration is controlled by a carotenoid-binding protein, a product of the Yellow blood gene.
Mechanisms for the uptake and transport of carotenoids, essential nutrients for humans, are not well understood in any animal system. The Y (Yellow blood) gene, a critical cocoon color determinant in the silkworm Bombyx mori, controls the uptake of carotenoids into the intestinal mucosa and the silk gland. Here we provide evidence that the Y gene corresponds to the intracellular carotenoid-binding protein (CBP) gene. In the Y recessive strain, the absence of an exon, likely due to an incorrect mRNA splicing caused by a transposon-associated genomic deletion, generates a nonfunctional CBP mRNA, resulting in colorless hemolymph and white cocoons. Enhancement of carotenoid uptake and coloration of the white cocoon was achieved by germ-line transformation with the CBP gene. This study demonstrates the existence of a genetically facilitated intracellular process beyond passive diffusion for carotenoid uptake in the animal phyla, and paves the way for modulating silk color and lipid content through genetic engineering.


Soybean Aphid (Hemiptera: Aphididae) Affects Soybean Spectral Reflectance.
Soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), is the most economically important insect pest of soybean in the north central United States. Scouting-based integrated pest management (IPM) programs could become more efficient and more widely adopted by using plant spectral reflectance to estimate soybean aphid injury. Our objective was to determine whether plant spectral reflectance is affected by soybean aphid feeding. Field trials were conducted in 2013 and 2014 using caged plots. Early-, late-, and noninfested treatments were established to create a gradient of soybean aphid pressure. Whole-plant soybean aphid densities were recorded weekly. Measurements of plant spectral reflectance occurred on two sample dates per year. Simple linear regression models were used to test the effect of cumulative aphid-days (CAD) on plant spectral reflectance at 680 nm (RED) and 800 nm (NIR), normalized difference vegetation index (NDVI), and relative chlorophyll content. Data indicated that CAD had no effect on canopy-level RED reflectance, but CAD decreased canopy-level NIR reflectance and NDVI. Canopy- and leaf-level measurements typically indicated similar plant spectral response to increasing CAD. CAD generally had no effect on relative chlorophyll content. The present study provides the first documentation that remote sensing holds potential for detecting changes in plant spectral reflectance induced by soybean aphid. The use of plant spectral reflectance in soybean aphid management may assist future IPM programs to reduce sampling costs and prevent prophylactic insecticide sprays.


Improved algorithm for quantitative analyses of infrared spectra of multicomponent gas mixtures with unknown compositions.
We present a major improvement of an algorithm based on a spectral library search for the quantitative analysis of multicomponent gas samples with unknown compositions. A quantitative spectral database of infrared spectra is used as a training set to compute regression coefficients. Concentrations are computed in the principal component space via principal component regression (PCR). In addition to previous algorithms, we introduce a rating for each candidate substance depending on the concentration found with PCR and a filter that removes candidates that are predicted with negative concentrations if their rating is below a certain threshold. Negative concentrations arise when the measured spectrum contains components that are not contained in the database. The PCR is recomputed until all candidates have a rating above the threshold. Then an adaptive filter "subtracts" the substance with the highest rating from both the measured spectrum and the library and appends it to a hit list. The iteration of this procedure directly produces a list of substances in order of descending importance (i.e., contribution to the measured absorbance) with their corresponding concentrations. The algorithm is tested on spectra of multicomponent surgical smoke samples. The four main components (water, methane, ethane, and ethene) are identified correctly (within the top 5 of the hit list) for an appropriate choice of the rating threshold. The algorithm describes the composition of the smoke sample correctly despite the presence of features in the spectrum that cannot be explained by the spectrum of any single substance present in the database.


[Cardiac toxicity of 5-fluorouracil. Review of the literature, 5 new cases].
The toxic effects of 5-fluorouracil - an antimitotic drug widely used in the treatment of cancer - mainly affect the digestive tract and the blood. The 5 new cases presented here may be added to the 57 cases of cardiotoxicity reported in the literature. The clinical manifestations always consist of constrictive chest pain resembling angina pectoris and associated with disorders of repolarization on electrocardiographic tracing recorded during the painful episodes. The outcome is usually favourable after discontinuation of treatment, but it may also be fatal. Reintroduction of the drug in 28 patients resulted in myocardial necrosis in 4 cases and in death due to cardiogenic shock in 4 cases. The frequency of such side-effects does not seem to be influenced by age, sex, route of administration and previous pathology including cardiovascular diseases. They usually occur at the beginning of treatment irrespective of the dose administered. The mechanism through which 5-fluorouracil exerts its cardiotoxic effects is unknown, and 3 hypothesis have been put forward: an immunoallergic reaction after a sensitization period, a coronary spasm directly induced by the drug or due to the release of a vasopressive substance, or a direct toxic effect on the myocardium and pericardium.


A Haemophilus sp. dominates the microbiota of sputum from UK adults with non-severe community acquired pneumonia and chronic lung disease.
The demographics and comorbidities of patients with community acquired pneumonia (CAP) vary enormously but stratified treatment is difficult because aetiological studies have failed to comprehensively identify the pathogens. Our aim was to describe the bacterial microbiota of CAP and relate these to clinical characteristics in order to inform future trials of treatment stratified by co-morbidity. CAP patients were prospectively recruited at two UK hospitals. We used 16S rRNA gene sequencing to identify the dominant bacteria in sputum and compositional data analysis to determine associations with patient characteristics. We analysed sputum samples from 77 patients and found a Streptococcus sp. and a Haemophilus sp. were the most relatively abundant pathogens. The Haemophilus sp. was more likely to be dominant in patients with pre-existing lung disease, and its relative abundance was associated with qPCR levels of Haemophilus influenzae. The most abundant Streptococcus sp. was associated with qPCR levels of Streptococcus pneumoniae but dominance could not be predicted from clinical characteristics. These data suggest chronic lung disease influences the microbiota of sputum in patients with CAP. This finding could inform a trial of stratifying empirical CAP antibiotics to target Haemophilus spp. in addition to Streptococcus spp. in those with chronic lung disease.


Randot stereoacuity does not accurately predict ability to perform two practical tests of depth perception at a near distance.
It is common practice to administer stereopsis tests such as the Randot Stereotest to prospective employees for occupations requiring depth perception. However, there is no evidence that stereoacuity measured with tests such as the Randot Stereotest will predict an individual's ability to perform a depth perception task at near. Forty-eight people with normal binocular vision were tested on 2 practical depth perception tests, and their stereoacuity was measured with the Randot Stereotest. There was little correlation between stereoacuity and either of the practical tasks (r<+/-0.1). These results show that Randot stereoacuity does not reliably predict depth perception ability for people who enjoy normal binocular vision. A better method for determining depth perception ability might be to issue a practical depth perception task.