Insertional polymorphisms of endogenous feline leukemia viruses.
The number, chromosomal distribution, and insertional polymorphisms of endogenous feline leukemia viruses (enFeLVs) were determined in four domestic cats (Burmese, Egyptian Mau, Persian, and nonbreed) using fluorescent in situ hybridization and radiation hybrid mapping. Twenty-nine distinct enFeLV loci were detected across 12 of the 18 autosomes. Each cat carried enFeLV at only 9 to 16 of the loci, and many loci were heterozygous for presence of the provirus. Thus, an average of 19 autosomal copies of enFeLV were present per cat diploid genome. Only five of the autosomal enFeLV sites were present in all four cats, and at only one autosomal locus, B4q15, was enFeLV present in both homologues of all four cats. A single enFeLV occurred in the X chromosome of the Burmese cat, while three to five enFeLV proviruses occurred in each Y chromosome. The X chromosome and nine autosomal enFeLV loci were telomeric, suggesting that ectopic recombination between nonhomologous subtelomeres may contribute to enFeLV distribution. Since endogenous FeLVs may affect the infectiousness or pathogenicity of exogenous FeLVs, genomic variation in enFeLVs represents a candidate for genetic influences on FeLV leukemogenesis in cats.


Major cardiovascular adverse events in older adults with early-stage triple-negative breast cancer treated with adjuvant taxane + anthracycline versus taxane-based chemotherapy regimens: A SEER-medicare study.
Triple-negative breast cancer (TNBC) is more aggressive as compared to other subtypes of breast cancer with characteristic metastatic patterns and a poor prognosis. The standard of care for early-stage TNBC is historically anthracycline and taxane-based chemotherapy (ATAX). Despite the effectiveness of this regimen, anthracyclines carry a small but important risk of cardiotoxicity, which is specifically a concern in the older population. This study evaluates major adverse cardiovascular events (MACE) in older women with TNBC treated with ATAX compared to taxane-based chemotherapy (TAX). Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified women aged 66 and older with TNBC diagnosed between 2010 and 2015 (N = 2215). We compared patient and clinical characteristics according to adjuvant chemotherapy regimen (chemotherapy versus no chemotherapy and ATAX versus TAX). Logistic regression was performed to estimate the odds ratios (OR) and 95% confidence intervals (CIs), Kaplan-Meier survival curves were generated to estimate three-year overall survival (OS) and cancer specific survival (CSS). Cox proportional hazards models were used to analyze OS and CSS while controlling for patient and tumor characteristics. MACE was defined as acute myocardial infarction, heart failure, potentially fatal arrhythmia, and cerebral vascular incidence. Few patients experienced a cardiac death and therefore this was excluded in the analysis. Of the 2215 patients in our cohort, most patients (n = 1334; 60.26%) received TAX compared to ATAX (n = 881; 39.78%). Patients who received ATAX were not statistically significantly more likely than those who received TAX to experience acute myocardial infarction, cerebral vascular accident (CVA), or potentially fatal arrhythmia when controlling for traditional risk factors. Among patients who experienced MACE, there was no difference in OS or CSS in patients who received TAX vs ATAX. Patients who received ATAX were less likely to develop heart failure than those who received TAX (OR 0.63, 95% CI [0.45-0.88], p < 0.01). Patients who developed MACE and who were > 76 years old had worse OS compared to those who experienced MACE and were age 66-75 years old (HR 1.67, 95% CI [1.07-2.62], p = 0.02). Among older women with TNBC, receipt of adjuvant chemotherapy with ATAX was not associated with increased risk of major adverse cardiac events. For those who experienced a cardiac event, there was no difference in survival amongst those who received TAX vs ATAX. Other factors including additional chemotherapy toxicities should be investigated as a potential etiology for the inferior OS previously observed with ATAX vs TAX in older women with node negative or 1-3 positive lymph nodes.


Immunologic suppression after oral administration of antigen. I. Specific suppressor cells formed in rat Peyer's patches after oral administration of sheep erythrocytes and their systemic migration.
Rats given 10(10) sheep erythrocytes (SRBC) orally were found to contain specific suppressor cells to SRBC in their Peyer's patches (PP) and mesenteric lymph nodes (MLN) after 2 days of feeding. After 4 days of feeding, similar suppressor cells were found in the thymus and spleen, but they were missing in the PP or MLN. These suppressor cells effectively blocked IgM and IgG plaque-forming cell responses to SRBC in Mishell-Dutton cultures and delayed-type-hypersensitivity responses to SRBC when transferred to syngeneic recipients, but they did not affect responses to horse erythrocytes. The orally induced specific suppressor cells appeared to be T2 cells since their activity was eliminated by in vivo treatment of SRBC-fed rats with anti-rat lymphocyte serum but not by adult thymectomy. Because carrageenan partially relieved the suppression observed in culture, the actual suppressive mechanism may also involve a macrophage.


Prox1 ablation in hepatic progenitors causes defective hepatocyte specification and increases biliary cell commitment.
The liver has multiple functions that preserve homeostasis. Liver diseases are debilitating, costly and often result in death. Elucidating the developmental mechanisms that establish the liver's architecture or generate the cellular diversity of this organ should help advance the prevention, diagnosis and treatment of hepatic diseases. We previously reported that migration of early hepatic precursors away from the gut epithelium requires the activity of the homeobox gene Prox1. Here, we show that Prox1 is a novel regulator of cell differentiation and morphogenesis during hepatogenesis. Prox1 ablation in bipotent hepatoblasts dramatically reduced the expression of multiple hepatocyte genes and led to very defective hepatocyte morphogenesis. As a result, abnormal epithelial structures expressing hepatocyte and cholangiocyte markers or resembling ectopic bile ducts developed in the Prox1-deficient liver parenchyma. By contrast, excessive commitment of hepatoblasts into cholangiocytes, premature intrahepatic bile duct morphogenesis, and biliary hyperplasia occurred in periportal areas of Prox1-deficient livers. Together, these abnormalities indicate that Prox1 activity is necessary to correctly allocate cell fates in liver precursors. These results increase our understanding of differentiation anomalies in pathological conditions and will contribute to improving stem cell protocols in which differentiation is directed towards hepatocytes and cholangiocytes.


Surgical treatment of obstructive sleep apnea: upper airway and maxillomandibular surgery.
Upper airway surgery is an important treatment option for patients with obstructive sleep apnea (OSA), particularly for those who have failed or cannot tolerate positive airway pressure therapy. Surgery aims to reduce anatomical upper airway obstruction in the nose, oropharynx, and hypopharynx. Procedures addressing nasal obstruction include septoplasty, turbinectomy, and radiofrequency ablation (RF) of the turbinates. Surgical procedures to reduce soft palate redundancy include uvulopalatopharyngoplasty, uvulopalatal flap, laser-assisted uvulopalatoplasty, and RF of the soft palate with adenotonsillectomy. More significant, however, particularly in cases of severe OSA, is hypopharyngeal or retrolingual obstruction related to an enlarged tongue, or more commonly due to maxillomandibular deficiency. Surgeries in these cases are aimed at reducing the bulk of the tongue base or providing more space for the tongue in the oropharynx so as to limit posterior collapse during sleep. These procedures include genioglossal advancement, hyoid suspension, distraction osteogenesis, tongue RF, lingualplasty, and maxillomandibular advancement. Successful surgery depends on proper patient selection, proper procedure selection, and experience of the surgeon. Most surgeries are done in combination and in a multistep manner, with maxillomandibular advancement typically being reserved for refractory or severe OSA, or for those with obvious and significant maxillomandibular deficiency. Although not without risks and not as predictable as positive airway pressure therapy, surgery remains an important therapeutic consideration in all patients with OSA. Current research aims to optimize the success of these procedures by identifying proper candidates for surgery, as well as to develop new invasive procedures for OSA treatment.


Oscillatory patterns in the electroencephalogram at sleep onset.
Falling asleep is a gradually unfolding process. We investigated the role of various oscillatory activities including sleep spindles and alpha and delta oscillations at sleep onset (SO) by automatically detecting oscillatory events. We used two datasets of healthy young males, eight with four baseline recordings, and eight with a baseline and recovery sleep after 40 h of sustained wakefulness. We analyzed the 2-min interval before SO (stage 2) and the five consecutive 2-min intervals after SO. The incidence of delta/theta events reached its maximum in the first 2-min episode after SO, while the frequency of them was continuously decreasing from stage 1 onwards, continuing over SO and further into deeper sleep. Interestingly, this decrease of the frequencies of the oscillations were not affected by increased sleep pressure, in contrast to the incidence which increased. We observed an increasing number of alpha events after SO, predominantly frontally, with their prevalence varying strongly across individuals. Sleep spindles started to occur after SO, with first an increasing then a decreasing incidence and a continuous decrease in their frequency. Again, the frequency of the spindles was not altered after sleep deprivation. Oscillatory events revealed derivation dependent aspects. However, these regional aspects were not specific of the process of SO but rather reflect a general sleep related phenomenon. No individual traits of SO features (incidence and frequency of oscillations) and their dynamics were observed. Delta/theta events are important features for the analysis of SO in addition to slow waves.


Effects of Stocking Rate and Environmental Enrichment on the Ontogeny of Pecking Behavior of Laying Hen Pullets Confined in Aviary Compartments during the First 4 Weeks of Life.
The objective of this study was to describe the ontogeny of the severe feather pecking (SFP), gentle feather pecking (GFP), aggressive pecking (AP), and enrichment pecking (EP) of non-beak-trimmed Lohmann Brown (LB)-pullets during the first 4 weeks of life (observation on 1st, 8th, 15th, 22nd, and 29th days of life) while they were kept within the compartments of a commercial rearing aviary (without access to a litter area). All chicks were placed into compartments of the middle tier of the aviary on the 1st day of life. On the 10th day of life, half of the chicks of each compartment were moved into the compartments of the lower tier. The aviary floor was covered with chick paper before the placement of the chicks and fully or partially removed from the 15th day of life onwards. The pecking behavior patterns were observed in three experimental groups (EG): NE (not enriched): group size until/after 10th day of life: 230/115; 120.8/60.4 birds/m2, no enrichment; EL (enriched, low stocking rate): group size until/after 10th day of life: 203/101, 106.6/53.6 birds/m2; and EH (enriched, high stocking rate): group size until/after 10th day of life: 230/115;120.8/60.4 birds/m2, both pecking stones and blocks as enrichment) in two rearing periods. For each pecking behavior pattern, an independent regression model with the parameters EG, chick paper, observation day, and functional area was estimated. GFP, SFP, and EP increased with age during the observation. The AP rate was highest in all EGs on the first day of life and decreased during the observation period. A pairwise comparison of NE (high stocking rate without enrichment) with EH (high stocking rate with enrichment and with EL (low stocking rate with enrichment) showed a significant effect of the EG on pecking behavior, with more SFP, AP, and GFP in NE. There were no differences between EL and EH, indicating that the provision of pecking materials had more influence than the stocking rate. However, we presumed that the difference between the stocking rates were too small to observe an effect. AP, SFP, and GFP were significantly higher on wired slats, as compared to the perches and the vicinity of the enrichment materials. The enrichment materials were suitable and intensely used by the pullets. The provision of pecking blocks and pecking stones was recommended as a preventive measure from the first day of life onwards for pullets housed in commercial rearing aviaries. There was no effect of reduced stocking rate, most likely due to the low variation in stocking rates.


Does body mass index/morbid obesity influence outcome in patients who undergo pancreatoduodenectomy for pancreatic adenocarcinoma?
The obesity epidemic coupled with epidemiologic evidence of the link between pancreatic cancer and obesity has raised the interest in the impact of body mass index (BMI) on outcomes for resected pancreatic cancer. All patients who underwent pancreatoduodenectomy (PD) for pancreatic adenocarcinoma from 1981 to 2007 were categorized into four groups according to their BMI (<25, 25 to <30, 30 to <35, and ≥35). Associations of these BMI groups with perioperative (operating time, blood loss, complications, in-hospital mortality), pathologic (tumor diameter, tumor stage, differentiation, lymph node status, R0 status) features and long-term patient outcome were evaluated using Kruskal-Wallis and chi-square tests, logistic regression, and Cox proportional hazards regression. A second set of analyses were performed by dichotomizing patients into morbidly obese (BMI ≥ 35) in comparison to the rest. Of the 586 consecutive patients studied, there were 232 (39.6%) with BMI <25, 232 (39.6%) with BMI 25 to <30, 89 (15.2%) with BMI 30 to <35, and 33 (5.6%) with BMI ≥ 35. Operating time (P = 0.003) and intraoperative blood loss (P < 0.001) increased with BMI, although none of the remaining perioperative features differed significantly among the BMI groups. Similarly, there were no significant associations between BMI group and the pathological features studied, particularly lymph node status (P= 0.98). BMI was not associated with lymph node status even after adjusting for tumor diameter. All analyses were repeated for the morbidly obese. Cox regression did not demonstrate an impact of BMI or morbid obesity on overall or disease-free survival. BMI (and morbid obesity) does not appear to influence long-term outcomes for patients undergoing PD. Surgeons should be vigilant of the greater risk of perioperative blood loss with increasing BMI.


Left ventricular function in diabetes mellitus. I: Methodology, and prevalence and spectrum of abnormalities.
Frequent abnormalities of left ventricular function were detected in 212 established diabetic patients using non-invasive techniques. Diabetics without angina or heart failure (n = 185) were significantly different from normal subjects (n = 50) in beat-to-beat variation, ratio of pre-ejection period to left ventricular ejection time, pre-ejection period index, isovolumic relaxation time, and interval from minimal dimension to mitral valve opening. Diabetics with angina (n = 18) were similar to control subjects with angina (n = 25); they showed a significant dimension change during the isovolumic period as compared with other diabetics and normals. Sixteen diabetics without angina also showed outward motion during the isovolumic period (incoordinate relaxation) and 13 had abnormal systolic time intervals. Four diabetics suffered a myocardial infarction during the study period; all had previously shown incoordination. Comparison of diabetics with a diastolic blood pressure below 100 mmHg and between 100 and 125 mmHg showed that the latter had a thicker posterior wall; the enlarged systolic dimension and reduced fractional shortening were the result of the inclusion of five of the 11 diabetic subjects with heart failure in the hypertensive group. Insulin-dependent diabetics tend to have more pronounced abnormalities of left ventricular function than those not requiring insulin. Patients selected from a diabetic clinic frequently have impaired left ventricular function, and ventricular hypertrophy, when present, in primarily caused by hypertension.


Transcranial Direct Current Stimulation vs Sham Stimulation to Treat Aphasia After Stroke: A Randomized Clinical Trial.
Aphasia is a debilitating language disorder for which behavioral speech therapy is the most efficient treatment, but therapy outcomes are variable and full recovery is not always achieved. It remains unclear if adjunctive brain stimulation (anodal transcranial direct current stimulation [A-tDCS]) applied during aphasia therapy can improve outcomes. To examine the futility of studying A-tDCS as an adjunctive intervention during speech therapy to improve speech production (naming) for individuals with long-term poststroke aphasia. Double-blinded, prospective randomized clinical trial using a futility design to test adjunctive A-tDCS during speech therapy. The setting was an outpatient clinic. Enrollment of individuals began in August 2012 and was completed in March 2017, and the duration of follow-up was 6 months. Analyses began in April 2017. The study recruited from a volunteer sample, and 89 patients were screened. Patients with long-term (>6 months) aphasia due to 1 previous left hemisphere stroke were enrolled. In comparing A-tDCS and sham tDCS, patients were matched based on site (University of South Carolina or Medical University of South Carolina), baseline age, type of aphasia, and aphasia severity. Outpatient speech therapy for 3 weeks (15 sessions, 45 minutes each) combined with either A-tDCS vs sham tDCS applied to preserved left temporal lobe regions. The primary outcome was the ability to name common objects, assessed twice before and after therapy. A total of 74 patients were enrolled. Participants had a mean (SD) age of 60 (10) years, had 15 (2) years of education, and were 44 (40) months from stroke onset. There were 52 men (70%) and 62 non-Hispanic white individuals (84%). Most were retired or not employed (59 [80%]). Broca aphasia was the most common aphasia type (39 [52.7%]). The adjusted mean (SE) change from pretreatment baseline in correct naming was 13.9 (2.4) words (95% CI, 9.0-18.7) for A-tDCS and 8.2 (2.2) words (95% CI, 3.8-12.6) for sham tDCS, with mean (SE) A-tDCS difference of 5.7 (3.3) words (95% CI, -0.9 to 12.3), indicating a relative 70% increase in correct naming for A-tDCS relative to sham. The futility hypothesis P value was .90, indicating failure to reject the null hypothesis and, therefore, providing no evidence that further study of A-tDCS is futile. No serious adverse events were associated with A-tDCS. Our findings provide motivation to proceed with another trial to study the effect of A-tDCS on the outcome of aphasia treatment in individuals poststroke. Anodal tDCS during speech therapy is feasible and potentially transformative for aphasia treatment and should be further studied. ClinicalTrials.gov Identifier: NCT01686373.


Validity of expert assigned retrospective estimates of occupational polychlorinated biphenyl exposure.
Assessment of retrospective exposures based on expert judgment in case-control studies is usually of unknown validity because of the difficulty in finding gold standards for comparison. We investigated the relationship between expert-assigned retrospective occupational polychlorinated biphenyl (PCB) exposure estimates and serum PCB concentrations. Analyses were conducted on a subset of cases (n = 94) and controls (n = 96) in the multi-center National Cancer Institute, Surveillance, Epidemiology, and End Results Case-Control Study of non-Hodgkin lymphoma. Based on the subjects' lifetime work histories, an industrial hygienist assigned each job a probability of PCB exposure [<5% (unexposed), 5-<50% (possibly exposed), ≥50% (probably exposed)]. Ordinary least squares regression was used to investigate associations between the probability rating and log-transformed lipid-adjusted serum levels of 14 PCB congeners and total PCBs (ΓPCBs). Compared to unexposed participants (n = 163), those with a probably exposed job (n = 7) had serum levels that were 87% higher for ΓPCBs (95% confidence interval: 1.33-2.62) and 38% of serum level variability was explained by the probability rating. Statistically significant associations between probability ratings and serum levels for 12 of 14 individual congeners were also observed. In summary, the observed contrast in PCB serum levels by probability rating provides support for the occupational PCB exposure assessment.


Effects of pulsatile administration of growth hormone (GH)-releasing hormone on short term linear growth in children with GH deficiency.
To assess the efficacy of GH-releasing hormone (GHRH) in the treatment of GH deficiency, we measured the effects of pulsatile iv GHRH administration on GH secretion, plasma levels of somatomedin-C (SmC), and short term linear growth (as determined by lower leg measurements) in seven GH-deficient children in a placebo-controlled study. Either GHRH, at a dose of 1 microgram/kg (seven patients), or 0.9% saline (NS; four of these patients) was given iv every 3 h for 9-12 days; all patients also received GH for a similar period. Lower leg length was measured every 3 weeks before and after each treatment. GHRH was more effective than placebo in accelerating linear growth (P less than 0.05). The responses, however, were heterogeneous; four of the children responded with accelerated growth, and three did not. Two of the children who failed to grow had no increase in plasma GH or SmC during GHRH administration, and one had an attenuated GH response. The four children who grew had induction of pulsatile GH secretion [mean peak GH, 10.4 +/- 1.3 (+/- SEM) ng/ml after GHRH vs. 1.5 +/- 0.5 ng/ml after NS; P less than 0.05] and elevation in SmC levels (maximum, 0.5 +/- 0.1 U/ml during GHRH vs. 0.19 +/- 0.05 during NS; P less than 0.01). The lower leg growth velocity during GHRH treatment (2.8 +/- 0.2 mm/3 weeks) was greater than their own basal rate (0.6 +/- 0.2 mm/3 weeks; P less than 0.01) or their growth during placebo treatment (0.4 +/- 0.2 mm/3 weeks; P less than 0.01). Thus, repeated administration of GHRH stimulated increases in GH and SmC in some but not all GH-deficient children. The growth response appears to be related to the magnitude of the GHRH-stimulated rise in GH levels. GHRH increases short term linear growth in some children with GH deficiency and holds promise as an alternative to GH as a form of therapy in these patients.


Mach-Zehnder interferometer switch with a high extinction ratio over a wide wavelength range.
We have realized a novel Mach-Zehnder interferometer (MZI) thermo-optic switch that can operate over a much wider wavelength range than a conventional MZI switch. We constructed the novel MZI switch by incorporating a phase-generating coupler (PGC) as an optical coupler. The PGC generates a nonlinear wavelength-dependent phase, which functions as a virtual wavelength-dependent delay part that cancels out the wavelength dependence of a MZI. We fabricated the novel MZI switch on a silica-based planar light-wave circuit and achieved a low insertion loss of less than 1.6 dB and a high extinction ratio of 30 dB over a wide wavelength range of 160 nm.


[Ocular and palpebral surgery: indications and limits].
Oculo-plastic surgery includes all the problems bound to the eyelids. In this presentation, we expose the most frequent oculo-palpebral pathologies, their treatment and some of the commonest complications. In all facial surgery, there is a plastic component, so it seems impossible to talk about this surgery without taking into account the cosmetical aspects.


Antimicrobial peptides from frog skin: biodiversity and therapeutic promises.
More than a thousand antimicrobial peptides (AMPs) have been reported in the last decades arising from the skin secretion of amphibian species. Generally, each frog species can express its own repertoire of AMPs (typically, 10-20 peptides) with differing sequences, sizes, and spectrum of action, which implies very rapid divergence, even between closely related species. Frog skin AMPs are highly potent against antibiotic-resistant bacteria, protozoa, yeasts, and fungi by permeating and destroying their plasma membrane and/or inactivating intracellular targets. These peptides have attracted considerable interest as a therapeutic alternative to conventional anti-infective agents. However, efforts to obtain a new generation of drugs using these peptides are still challenging because of high associated R&D costs due to their large size (up to 46 residues) and cytotoxicity. This review deals with the biodiversity of frog skin AMPs and assesses the therapeutic possibilities of temporins, the shortest AMPs found in the frog skin, with 8-17 residues. Such short sequences are easily amenable to optimization of the structure and to solution-phase synthesis that offer reduced costs over solid-phase chemistry.


The possible effect of topically applied azithromycin and moxifloxacin on the alleviation of uveitis.
To investigate the inhibitory effect of topically administered azithromycin (AZM), and moxifloxacin (MXF) against tumor necrosis factor-α (TNF-α) production in a rat model of endotoxin-induced uveitis (EIU). Thirty-six Wistar albino rats were divided into 6 equal groups. Groups 1, 2 and 3 were determined as sham, control group for topical AZM application and control group for topical MXF application, respectively. Sterile saline, topical AZM 1.5%, and topical MXF 0.5% were instilled 5 times daily for totally 6 days on both eyes of the rats in Group 4, Group 5, and Group 6, before and after inducing EIU by intravitreal injections of lipopolysaccharide, respectively. At 24 h after intravitreal injections, aqueous humor was collected from both eyes of each rat for the assessment of TNF-α concentration. Also, density of nuclear factor kappa B (NF-κB) in ciliary body, and the number of cells infiltrating the posterior segment of EIU rat eyes was assessed in one eye of each rat. There was a significant reduction in mean aqueous humor concentration of TNF-α in EIU rats pretreated with topical AZM in comparison with those pretreated with sterile saline (139 ± 38.6 in Group 4 vs. 72 ± 12.6 in Group 5, p = 0.006). There was also a marked decrease in mean aqueous humor concentration of TNF-α in EIU rats pretreated with topical MXF (139 ± 38.6 in Group 4 vs.86.1 ± 35.5 in Group 6, p = 0.025). Also, evident suppressions were determined in mean density of NF-κB, and in mean number of cells in EIU rats pretreated either with topical AZM, or topical MXF. Topically applied AZM or MXF may be beneficial in the suppression of TNF-α production in aqueous humor.


Nck adapter proteins: functional versatility in T cells.
Nck is a ubiquitously expressed adapter protein that is almost exclusively built of one SH2 domain and three SH3 domains. The two isoproteins of Nck are functionally redundant in many aspects and differ in only few amino acids that are mostly located in the linker regions between the interaction modules. Nck proteins connect receptor and non-receptor tyrosine kinases to the machinery of actin reorganisation. Thereby, Nck regulates activation-dependent processes during cell polarisation and migration and plays a crucial role in the signal transduction of a variety of receptors including for instance PDGF-, HGF-, VEGF- and Ephrin receptors. In most cases, the SH2 domain mediates binding to the phosphorylated receptor or associated phosphoproteins, while SH3 domain interactions lead to the formation of larger protein complexes. In T lymphocytes, Nck plays a pivotal role in the T cell receptor (TCR)-induced reorganisation of the actin cytoskeleton and the formation of the immunological synapse. However, in this context, two different mechanisms and adapter complexes are discussed. In the first scenario, dependent on an activation-induced conformational change in the CD3epsilon subunits, a direct binding of Nck to components of the TCR/CD3 complex was shown. In the second scenario, Nck is recruited to the TCR complex via phosphorylated Slp76, another central constituent of the membrane proximal activation complex. Over the past years, a large number of putative Nck interactors have been identified in different cellular systems that point to diverse additional functions of the adapter protein, e.g. in the control of gene expression and proliferation.


Diffusion and consumption of oxygen in the superfused retina of the drone (Apis mellifera) in darkness.
Double-barreled O2 microelectrodes were used to study O2 diffusion and consumption in the superfused drone (Apis mellifera) retina in darkness at 22 degrees C. Po2 was measured at different sites in the bath and retinas. It was found that diffusion was essentially in one dimension and that the rate of O2 consumption (Q) was practically constant (on the macroscale) down to Po2 s less than 20 mm Hg, a situation that greatly simplified the analysis. The value obtained for Q was 18 +/- 0.7 (SEM) microliter O2/cm3 tissue . min (n = 10), and Krogh's permeation coefficient (alpha D) was 3.24 +/- 0.18 (SEM) X 10(-5) ml O1/min . atm . cm (n = 10). Calculations indicate that only a small fraction of this Q in darkness is necessary for the energy requirements of the sodium pump. the diffusion coefficient (D) in the retina was measured by abruptly cutting off diffusion from the bath and analyzing the time-course of the fall in Po2 at the surface of the tissue. The mean value of D was 1.03 +/- 0.08 (SEM) X 10(-5) cm2/s (n = 10). From alpha D and D, the solubility coefficient alpha was calculated to be 54 +/- 4.0 (SEM) microliter O2 STP/cm3 . atm (n = 10), approximately 1.8 times that for water.


Review on the fate of organic micropollutants in wastewater treatment and water reuse with membranes.
A brief review of the fate of micropollutants in membrane-based wastewater treatment due to sorption, stripping, biological degradation/transformation and membrane separation is discussed, to give an overview of these technologies due to the growing importance for water reuse purposes. Compared with conventional activated sludge treatment (CAS) micropollutant removal in membrane bioreactor (MBR) is slightly improved due to complete suspended solids removal and increased sludge age. For discharge to sensitive receiving waters advanced treatment, such as post-ozonation or activated carbon adsorption, is recommended. In water reuse plants nanofiltration (NF) and reverse osmosis (RO) efficiently reject micropollutants due to size exclusions as well as electrostatic and hydrophobic effects reaching potable quality. To remove micropollutants fully, additionally post-ozone or the addition of powdered activated carbon (PAC) have to be applied, which in parallel also reduce NDMA precursors. The concentrate has to be treated if disposed to sensitive receiving waters due to its high micropollutant concentration and ecotoxicity potential. The present review summarizes principles and capabilities for the most important membrane-based applications for wastewater treatment, i.e. porous membranes in MBRs (micro- or ultrafiltration) and dense membrane applications (NF and RO) for water reuse.


Backbone, side chain and heme resonance assignment of the triheme cytochrome PpcA from Geobacter metallireducens in the oxidized state.
The bacterium Geobacter metallireducens is capable of transferring electrons to the cell exterior, a process designated extracellular electron transfer. This mechanism allows the microorganism to reduce extracellular acceptors such as Fe(III) (hydr)oxides and water toxic and/or radioactive contaminants including Cr(VI) and U(VI). It is also capable of oxidizing waste water aromatic organic compounds being an important microorganism for bioremediation of polluted waters. Extracellular electron transfer also allows electricity harvesting from microbial fuel cells, a promising sustainable form of energy production. However, extracellular electron transfer processes in this microorganism are still poorly characterized. The triheme c-type cytochrome PpcA from G. metallireducens is abundant in the periplasm and is crucial for electron transfer between the cytoplasm and the cell's exterior. In this work, we report near complete assignment of backbone, side chain and heme resonances for PpcA in the oxidized state that will permit its structure determination and identification of interactions with physiological redox partners.


Body mass index and anthropometric characteristics of the hand as risk factors for carpal tunnel syndrome.
Carpal tunnel syndrome (CTS) is the most common peripheral entrapment compressive neuropathy in the upper limbs. It is often correlated with personal factors of individuals, not only with certain medical conditions and jobs. The study aimed at clarifying the association of carpal tunnel syndrome with anthropometric characteristics of the hand and body mass index (BMI) as independent risk factors. A total of 100 subjects participated: 50 patients with electro-diagnostically confirmed CTS and 50 healthy volunteers without CTS symptoms as control group, each group including 37 women and 13 men. Height, weight, BMI, wrist depth and width, wrist index, hand shape index, digit index, palm length, palm width, third finger length and ratio of hand length to body height were assessed in all participants. To determine independent risk factors for CTS, multiple logistic regression was used. Wrist index and wrist width were significantly higher in CTS patients than in the control group. The estimated optimal threshold of wrist index for prediction of CTS was 0.69, above which the odds for CTS were estimated to increase 42-fold. Elevated BMI correlated with bilateral CTS in both genders. The study identified wrist index, BMI and ratio of hand length to body height ratio as independent risk factors for CTS.


Induction of NFATc2 expression by interleukin 6 promotes T helper type 2 differentiation.
Interleukin (IL)-6 is produced by professional antigen-presenting cells (APCs) such as B cells, macrophages, and dendritic cells. It has been previously shown that APC-derived IL-6 promotes the differentiation of naive CD4+ T cells into effector T helper type 2 (Th2) cells. Here, we have studied the molecular mechanism for IL-6-mediated Th2 differentiation. During the activation of CD4+ T cells, IL-6 induces the production of IL-4, which promotes the differentiation of these cells into effector Th2 cells. Regulation of IL-4 gene expression by IL-6 is mediated by nuclear factor of activated T cells (NFAT), as inhibition of NFAT prevents IL-6-driven IL-4 production and Th2 differentiation. IL-6 upregulates NFAT transcriptional activity by increasing the levels of NFATc2. The ability of IL-6 to promote Th2 differentiation is impaired in CD4+ T cells that lack NFATc2, demonstrating that NFATc2 is required for regulation of IL-4 gene expression by IL-6. Regulation of NFATc2 expression and NFAT transcriptional activity represents a novel pathway by which IL-6 can modulate gene expression.


Survey of Dental Implant and Restoration Selection by Prosthodontists in Dubai.
With various surgical and prosthetic component designs being introduced in dental implants, decisions have to be made when choosing a system and a certain prosthodontic protocol. A survey of implant prosthodontic specialists has not been previously performed in the Middle East. This study aimed to determine selection criteria and choice of dental implants and restorations by prosthodontic specialists in the Emirate of Dubai, United Arab Emirates. A validated 16-item questionnaire was used in the survey which included demographic information, implant training and experience, implant treatment planning, implant restoration, and implant system preference. The research protocol was approved by the Research and Ethics Committees of Hamdan Bin Mohammed College of Dental Medicine and Dubai Health Authority. Prosthodontists were identified from regulatory authority websites and contacted by e-mail with the questionnaire attached. A total of 84.6% (77) of the registered prosthodontists in Dubai completed the questionnaire with 66.2% reported practicing implant dentistry. Out of which, 54.9% reported surgically placing dental implants and 45.1% restore them only prosthetically. Prefabricated metal abutments were the most commonly selected abutments for single crowns (76.0%) and for fixed dental prostheses (66.7%). Screw retention is preferred mostly for single crowns (68.0%) and fixed dental prostheses (74.0%). Locators were the most commonly selected type of attachment for implant-retained/supported overdentures (49.0%). Conventional loading was the most selected type of loading in all oral conditions. Within the limitations of this study, it can be concluded that most prosthodontists in Dubai practice implant dentistry and more than half surgically place dental implants. Prefabricated metal abutments are the most selected type of abutments. Most prosthodontists use screw-retained implant restorations and prefer locator attachments for implant-retained/supported overdentures. Conventional loading is the most preferred implant loading method in all oral conditions. Implant company/system selections are various and there is no major preference for a certain system. The majority of prosthodontists select implant systems based on implant features, literature review, and simplicity of restorative kit.


From malnutrition to refeeding during anorexia nervosa.
Anorexia nervosa is one of the most common forms of malnutrition observed in Western society in individuals without physical diseases, with an average risk of mortality of 20% in a younger population aged between 15 and 25 years. It is characterised by an initial dramatic decrease in food intake that leads to profound depletion in muscle and fat mass. During the course of the disease, the resting energy expenditure decreases proportionally to the loss of lean body mass with a decrease in thyroid hormone secretion. The metabolic adaptation during anorexia nervosa is similar to that observed during starvation with a relative sparing of protein stores. After an initial weight loss, the total energy expenditure is similar to that in normal individuals, with a decrease in resting energy expenditure and an increased energy-related physical activity. At the end stage of wasting, however, physical activity dramatically decreases as well as energy intake. This metabolic adaptation of semi-starvation is impaired during refeeding with an increase in the thermic effect of food and a high risk of refeeding syndrome with severe hypophosphatemia.


[Significance of heterogenity in endothelium-dependent vasodilatation occurrence in healthy individuals with or without coronary risk factors].
Brachial artery flow-mediated dilation (FMD) is extensively used for non-invasive assessment of endothelial function. Traditionally, FMD is calculated as a percent change of arterial diameter from the baseline value at an arbitrary time point after cuff deflation (usually 60 seconds). Considerable individual differences in brachial artery temporal response to hyperemic stimulus have been observed, potentially influenced by the presence of atherosclerotic risk factors (RF). The importance of such differences for the evaluation of endothelial function has not been well established. The aim of the study was to determine the time course of maximal brachial artery endothelium-dependent dilation in healthy adults with and without RF, to explore the correlation of RF with brachial artery temporal response and to evaluate the importance of individual differences in temporal response for the assessment of endothelial function. A total of 115 healthy volunteers were included in the study. Out of them, 58 had no RF (26 men, mean age 44 +/-14 years) and 57 had at least one RF (29 men, mean age 45 +/-14 years). High-resolution color Doppler vascular ultrasound was used for brachial artery imaging. To determine maximal arterial diameter after cuff deflation and the time-point of maximal vasodilation off-line sequential measurements were performed every 10 seconds from 0 to 240 seconds after cuff release. True maximal FMD value was calculated as a percent change of the true maximal diameter from the baseline, and compared with FMD value calculated assuming that every participant reached maximal dilation at 60 seconds post cuff deflation (FMD60). Correlation of different RF with brachial artery temporal response was assessed. A maximal brachial artery endothelium-dependent vasodilation occurred from 30-120 seconds after cuff release, and the mean time of endothelium-dependent dilation was 68 +/-20 seconds. Individuals without RF had faster endothelium-dependent dilation (mean time 62 +/-17 seconds), and a shorter time-span (30 to 100 seconds), than participants with RF (mean time 75 +/-21 seconds, time-span 40 to 120 seconds) (p < 0.001). Time when the maximal endothelium-dependent dilation occurred was independently associated with age, serum lipid fractions (total cholesterol, LDL and HDL cholesterol), smoking, physical activity and C-reactive protein. True maximal FMD value in the whole group (6.7 +/-3.0%) was significantly higher (p < 0.001) than FMD60 (5.2 +/-3.5%). The same results were demonstrated for individuals with RF (4.9 +/- 1.7% vs 3.1 +/- 2.3%, p < 0.001) and without RF (8.4 +/- 2.9% vs 7.2 +/- 3.2%, p < 0.05). The temporal response of endothelium-dependent dilation is influenced by the presence of coronary FR and individually heterogeneous. When calculated according to the commonly used approach, i.e. 60 seconds after cuff deflation, FMD is significantly lower than the true maximal FMD. The routinely used measurement time-points for FMD assessment may not be adequate for the detection of true peak vasodilation in individual persons. More precise evaluation of endothelial function can be achieved with sequential measurement of arterial diameter after hyperemic stimulus.


Neonatal Abstinence Syndrome Practices in the United States.
To survey current practices for the treatment of neonatal abstinence syndrome (NAS) among institutions in the United States to identify changes in national practice over time. Previous NAS management reports were referenced in the development of our 26-question electronic survey, which was distributed in the fall of 2019 to pediatric practitioners of 2 national clinical pharmacy organizations via email list servers. Not all questions required a response and responses from incomplete surveys were included. Institution demographics and NAS management strategies, including location of care, observation period, and inpatient and outpatient pharmacotherapy, were queried. Seventy respondents representing institutions from all US geographic regions participated in the survey The most commonly reported inpatient observation durations were 3 (18 of 61, 29%) and 5 (22 of 61, 36%) days. Respondents indicated that neonates were typically transferred to the NICU if pharmacologic management was required (38 of 56, 68%). According to participants, first-line agents used for NAS management were morphine (45 of 56, 80%), methadone (5 of 56, 9%), clonidine (2 of 56, 4%), and buprenorphine (2 of 56, 4%). Among respondents, only 20% (11 of 56) reported that infants may be discharged home on pharmacotherapy, including morphine (n = 6), phenobarbital (n = 3), clonidine (n = 1), and methadone (n = 1). Opioids are the most commonly used first-line agents for NAS management in the United States. The primary site of NAS management is the inpatient setting, as only 20% of institutions report discharging patients on pharmacotherapy.


Health Literacy Assessment: Feasibility in a Breast Surgical Oncology Clinic
Health literacy is recognized as an integral component of high-quality health care. However, health literacy has been understudied in the context of cancer care delivery and surgical decision making. The goal of this article is to outline a process for implementation of a health literacy screening assessment within the routine practices of an academic breast surgical oncology clinic. The self-reported health literacy assessment is feasible, particularly with integration of the health literacy screen in the electronic health record. The authors' estimated clinic prevalence of low health literacy was 22%, which has numerous implications for communication and shared decision-making processes. .


In vivo postprandial lipid partitioning in liver and skeletal muscle in prediabetic and diabetic rats.
Insulin resistance and type 2 diabetes have been associated with ectopic lipid deposition. This study investigates the derangements in postprandial lipid handling in liver and skeletal muscle tissue at different stages during the pathogenesis of type 2 diabetes in a rat model. Four groups (n = 6) of male Zucker diabetic fatty rats were used for this study: prediabetic fa/fa rats and healthy fa/+ littermates at the age of 6 weeks, and diabetic fa/fa rats and healthy fa/+ littermates at the age of 12 weeks. In vivo (1)H-[(13)C] magnetic resonance spectroscopy measurements were performed in liver and tibialis anterior muscle at baseline and 4, 24 and 48 h after oral administration of 1.5 g [U-(13)C]algal lipid mixture per kilogram body weight. Total and (13)C-labelled intracellular lipid contents were determined from the magnetic resonance spectra. In both prediabetic and diabetic rats, total lipid contents in muscle and liver were substantially higher than in healthy controls and this was accompanied by a 2.3-fold greater postprandial lipid uptake in the liver (p < 0.001). Interestingly, in prediabetic rats, skeletal muscle appeared to be protected from excess lipid uptake whereas after developing overt diabetes muscle lipid uptake was 3.4-fold higher than in controls (p < 0.05). Muscle lipid use was significantly lower in prediabetic and diabetic muscle, indicative of impairments in lipid oxidation. In vivo postprandial lipid handling is disturbed in both liver and skeletal muscle tissue in prediabetic and diabetic rats, but the uptake of dietary lipids in muscle is only increased after the development of overt diabetes.


Identifying mouse developmental essential genes using machine learning.
The genes that are required for organismal survival are annotated as 'essential genes'. Identifying all the essential genes of an animal species can reveal critical functions that are needed during the development of the organism. To inform studies on mouse development, we developed a supervised machine learning classifier based on phenotype data from mouse knockout experiments. We used this classifier to predict the essentiality of mouse genes lacking experimental data. Validation of our predictions against a blind test set of recent mouse knockout experimental data indicated a high level of accuracy (>80%). We also validated our predictions for other mouse mutagenesis methodologies, demonstrating that the predictions are accurate for lethal phenotypes isolated in random chemical mutagenesis screens and embryonic stem cell screens. The biological functions that are enriched in essential and non-essential genes have been identified, showing that essential genes tend to encode intracellular proteins that interact with nucleic acids. The genome distribution of predicted essential and non-essential genes was analysed, demonstrating that the density of essential genes varies throughout the genome. A comparison with human essential and non-essential genes was performed, revealing conservation between human and mouse gene essentiality status. Our genome-wide predictions of mouse essential genes will be of value for the planning of mouse knockout experiments and phenotyping assays, for understanding the functional processes required during mouse development, and for the prioritisation of disease candidate genes identified in human genome and exome sequence datasets.


Graph convolutional network approach applied to predict hourly bike-sharing demands considering spatial, temporal, and global effects.
Solving the supply-demand imbalance is the most crucial issue for stable implementation of a public bike-sharing system. This gap can be reduced by increasing the accuracy of demand prediction by considering spatial and temporal properties of bike demand. However, only a few attempts have been made to account for both features simultaneously. Therefore, we propose a prediction framework based on graph convolutional networks. Our framework reflects not only spatial dependencies among stations, but also various temporal patterns over different periods. Additionally, we consider the influence of global variables, such as weather and weekday/weekend to reflect non-station-level changes. We compare our framework to other baseline models using the data from Seoul's bike-sharing system. Results show that our approach has better performance than existing prediction models.


Digital Health: Should We Be Concerned?
Type "health and fitness apps" into any search engine, and thousands of options will appear-so many, in fact, that people can now measure their own heart rate, sleep habits, and dozens of other health parameters that once required a doctor's visit. While anecdotes of a personal health device capturing early signs of disease may garner media attention, the increasing quantification of human physiology can have downsides. In essence, the enhanced ability to assess surrogate measures of health, such as temperature, minute-to-minute blood pressure, and genomics, are an expansion of anticipatory health-that is, an attempt to detect and avoid events that might happen in the future. While patients used to seek out doctors when they were sick, digital tools will send increasing numbers of people to their physicians before they are sick. In a Cartesian model of the human body, wherein one system could potentially be fixed independent of another system, having more data may be beneficial. The human body, however, is far more complex than any Cartesian model could explain. This article explores the limitations of digital devices to improve health.


The Decline in Community Preceptor Teaching Activity: Exploring the Perspectives of Pediatricians Who No Longer Teach Medical Students.
Difficulty in recruiting and retaining community preceptors for medical student education has been described in the literature. Yet little, if any, information is known about community outpatient preceptors who have stopped or decreased teaching time with students. This study aimed to examine these preceptors' perspectives about this phenomenon. Using a phenomenology framework, this multi-institutional qualitative study used semistructured interviews with community pediatric preceptors who had stopped or reduced teaching time with medical students. Interviews were conducted between October 2017 and January 2018 and transcribed verbatim. Interviews explored factors for engaging in teaching, or decreasing or ceasing teaching, that would enable future teaching. An initial code book was developed and refined as data were analyzed to generate themes. Twenty-seven community pediatricians affiliated with 10 institutions participated. Thirty-seven codes resulted in 4 organizing themes: evolution of health care, personal barriers, educational system, and ideal situations to recruit and retain preceptors, each with subthemes. From the viewpoints of physicians who had decreased or stopped teaching students, this study more deeply explores previously described reasons contributing to the decline of community preceptors, adds newly described barriers, and offers strategies to help counter this phenomenon based on preceptors' perceptions. These findings appear to be manifestations of deeper issues including the professional identify of clinical educators. Understanding the barriers and strategies and how they relate to preceptors themselves should better inform education leaders to more effectively halt the decline of community precepting and enhance the clinical precepting environment for medical students.


Angiogenesis Inhibitors in NSCLC.
Angiogenesis is a complex biological process that plays a relevant role in sustaining the microenvironment, growth, and metastatic potential of several tumors, including non-small cell lung cancer (NSCLC). Bevacizumab was the first angiogenesis inhibitor approved for the treatment of patients with advanced NSCLC in combination with chemotherapy; however, it was limited to patients with non-squamous histology and first-line setting. Approval was based on the results of two phase III trials (ECOG4599 and AVAIL) that demonstrated an improvement of about two months in progression-free survival (PFS) in both trials, and in the ECOG4599 trial, an improvement in overall survival (OS) also. Afterwards, other antiangiogenic agents, including sunitinib, sorafenib, and vandetanib have been unsuccessfully tested in first and successive lines. Recently, two new antiangiogenic agents (ramucirumab and nintedanib) produced a significant survival benefit in second-line setting. In the REVEL study, ramucirumab plus docetaxel prolonged the median OS of patients with any histology NSCLC when compared with docetaxel alone (10.4 versus 9.1 months, hazard ratio (HR) 0.857, p = 0.0235). In the LUME-Lung 1 study, nintedanib plus docetaxel prolonged the median PFS of patients with any tumor histology (p = 0.0019), and improved OS (12.6 versus 10.3 months) in patients with adenocarcinoma. As a result, it became a new option for the second-line treatment of patients with advanced NSCLC and adenocarcinoma histology. Identifying predictive biomarkers to optimize the benefit of antiangiogenic drugs remains an ongoing challenge.


Slowdown promotes muscle integrity by modulating integrin-mediated adhesion at the myotendinous junction.
The correct assembly of the myotendinous junction (MTJ) is crucial for proper muscle function. In Drosophila, this junction comprises hemi-adherens junctions that are formed upon arrival of muscles at their corresponding tendon cells. The MTJ mainly comprises muscle-specific alphaPS2betaPS integrin receptors and their tendon-derived extracellular matrix ligand Thrombospondin (Tsp). We report the identification and functional analysis of a novel tendon-derived secreted protein named Slowdown (Slow). Homozygous slow mutant larvae exhibit muscle or tendon rupture, sluggish larval movement, partial lethality, and the surviving adult flies are unable to fly. These defects result from improper assembly of the embryonic MTJ. In slow mutants, Tsp prematurely accumulates at muscle ends, the morphology of the muscle leading edge changes and the MTJ architecture is aberrant. Slow was found to form a protein complex with Tsp. This complex is biologically active and capable of altering the morphology and directionality of muscle ends. Our analysis implicates Slow as an essential component of the MTJ, crucial for ensuring muscle and tendon integrity during larval locomotion.


[Benign paroxysmal positional vertigo of the horizontal canal].
The benign positional vertigo of the horizontal canal seems to find its origins in a canalolithiasis. The diagnosis is usually easy when its characteristics are perfectly known. A horizontal nystagmus does not always mean that the vertigo is of a central origin. This canal is exclusively connected, via the brainstem, to the external and internal oculomotor muscles so that the movement obtained by its stimulation can only be horizontal! This is quite different from what is obtained for the posterior canal, which is connected to various oculomotor muscles. Specific therapeutic maneuvers have to be carried out to be efficient: if properly performed, the otoconias, heavy particles sensitive to gravity, are easily mobilized. This paper describes the pathophysiology of the positional vertigo of the horizontal canal, diagnosis of its two presentations, and therapeutic possibilities.


Abelson virus transformation of an interleukin 2-dependent antigen-specific T-cell line.
Abelson murine leukemia virus (A-MuLV) carries the gene v-abl, one of a group of oncogenes with structural and functional (tyrosine kinase) homology to three growth factor receptors. Work in this and other laboratories has shown that A-MuLV infection can render myeloid and lymphoid cells independent of the growth factors interleukin 3 and granulocyte-macrophage colony-stimulating factor. We have now shown that v-abl can also relieve interleukin 2 (IL-2) dependence in T cells. We infected a cloned IL-2-dependent antigen-specific cell line. Transformed cells were generated which were factor independent and tumorigenic. The transformants each bore unique v-abl DNA inserts and expressed v-abl mRNA. No elevation of expression of either IL-2 or its receptor could be detected in these cells. Thus, A-MuLV can short-circuit the dependence of hematopoietic cells on IL-2, IL-3, and possibly granulocyte-macrophage colony-stimulating factor, none of whose receptors are known to be of the tyrosine kinase type.


Lipopolysaccharides of Pseudomonas spp. that stimulate plant growth: composition and use for strain identification.
The outer membrane proteins of a series of fluorescent, root-colonizing, plant-growth-stimulating Pseudomonas spp. having been characterized (L. A. de Weger et al., J. Bacteriol. 165:585-594, 1986), the lipopolysaccharides (LPSs) of these strains were examined. The chemical composition of the LPSs of the three best-studied plant-growth-stimulating Pseudomonas strains WCS358, WCS361, and WCS374 and of P. aeruginosa PAO1 as a reference strain was determined and appeared to differ from strain to strain. The 2,6-dideoxy-2-aminosugar quinovasamine was the most abundant compound in the LPS of strain WCS358. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified LPS and of proteinase K-treated cell envelopes revealed ladderlike patterns for most of these strains. These patterns were not substantially influenced by differences in culture conditions. Analysis of proteinase K-treated cell envelopes of 24 root-colonizing Pseudomonas spp. revealed a unique band pattern for each strain, suggesting a great variety in the LPS structures present in these root colonizers. Therefore, electrophoretic analysis of LPS can be used for characterization and identification of the fluorescent root-colonizing Pseudomonas strains.


Betulinic acid and betulin ameliorate acute ethanol-induced fatty liver via TLR4 and STAT3 in vivo and in vitro.
Ethanol consumption leads to many kinds of liver injury and suppresses innate immunity, but the molecular mechanisms have not been fully delineated. The present study was conducted to determine whether betulinic acid (BA) or betulin (BT) would ameliorate acute ethanol-induced fatty liver in mice, and to characterize whether Toll like receptor 4 (TLR4) and signal transducer and activator of transcription 3 (STAT3) were involved in ethanol-stimulated hepatic stellate cells (HSCs). EtOH (5mg/kg) and BA or BT (20 or 50mg/kg) were applied in vivo, while EtOH (50mM) and BA or BT (12.5 or 25μM) were applied in vitro. Administration of BA or BT significantly prevented the increases of serum ALT and AST caused by ethanol, as well as serum TG. Supplement of BA or BT prevented ethanol-induced acidophilic necrosis, increased hepatocyte nuclei and stromal inflammation infiltration as indicated by liver histopathological studies. Administration of BA or BT significantly decreased CYP2E1 activities and expression of SREBP-1caused by ethanol, however, lower dosage of BA or BT showed slight effects on CYP2E1 activity or expression of SREBP-1c. BA or BT administration significantly decreased the expression of TLR4, and increased the phosphorylation of STAT3. In vitro, BA or BT treatment reduced the expressions of α-SMA and collagen-I in ethanol-stimulated HSCs via regulation of TLR4 and STAT3, coincided with in vivo. All of these findings demonstrated that BA or BT might ameliorate acute ethanol-induced fatty liver via TLR4 and STAT3 in vivo and in vitro, promising agents for ethanol-induced fatty liver therapies.


Electrochemicolor Imaging Using an LSI-Based Device for Multiplexed Cell Assays.
Multiplexed bioimaging systems have triggered the development of effective assays, contributing new biological information. Although electrochemical imaging is beneficial for quantitative analysis in real time, monitoring multiple cell functions is difficult. We have developed a novel electrochemical imaging system, herein, using a large-scale integration (LSI)-based amperometric device for detecting multiple biomolecules simultaneously. This system is designated as an electrochemicolor imaging system in which the current signals from two different types of biomolecules are depicted as a multicolor electrochemical image. The mode-selectable function of the 400-electrode device enables the imaging system and two different potentials can be independently applied to the selected electrodes. The imaging system is successfully applied for detecting multiple cell functions of the embryonic stem (ES) cell and the rat pheochromocytoma (PC12) cell aggregates. To the best of our knowledge, this is the first time that a real-time electrochemical mapping technique for multiple electroactive species, simultaneously, has been reported. The imaging system is a promising bioanalytical method for exploring complex biological phenomena.


Kidney Transplantation Among the Elderly: Challenges and Opportunities to Improve Outcomes.
Elderly patients (>65 years old) represent the fastest growing population among the ESRD patients and those awaiting kidney transplantation. There is ample evidence to suggest that kidney transplant in the elderly population offers the best chance of survival and improves health-related quality of life compared to remaining on dialysis. Although all these emerging facts are encouraging, this population brings with them complex medical problems including frailty, cognitive impairment, and multiple comorbidities. These issues can be barriers to transplantation and threaten the well-being of the patients after transplantation. Furthermore, aging results in changes to the immune system and affects the pharmacokinetics of immunosuppressants. All these changes can increase risk of complications such as infections and malignancy. Because death with a functioning graft is a common cause of graft loss, the new kidney allocation system has been implemented in an attempt to maximize allograft utilization and minimize unrealized graft years. This may result in longer wait-times for the elderly. In this review, we will highlight the barriers to kidney transplant, characterize transplant-related issues in the elderly, and propose alternative strategies under the new allocation system.


Loading forces in shallow water running in two levels of immersion.
To analyse the vertical and anteroposterior components of the ground reaction force during shallow water running at 2 levels of immersion. Twenty-two healthy adults with no gait disorders, who were familiar with aquatic exercises. Subjects performed 6 trials of water running at a self-selected speed in chest and hip immersion. Force data were collected through an underwater force plate and running speed was measured with a photocell timing light system. Analysis of covariance was used for data analysis. Vertical forces corresponded to 0.80 and 0.98 times the subject's body weight at the chest and hip level, respectively. Anteroposterior forces corresponded to 0.26 and 0.31 times the subject's body weight at the chest and hip level, respectively. As the water level decreased the subjects ran faster. No significant differences were found for the force values between the immersions, probably due to variability in speed, which was self-selected. When thinking about load values in water running professionals should consider not only the immersion level, but also the speed, as it can affect the force components, mainly the anteroposterior one. Quantitative data on this subject could help professionals to conduct safer aqua-tic rehabilitation and physical conditioning protocols.


Correspondence analysis as a screening method for indicants for clinical diagnosis.
In clinical diagnosis, a patient's symptoms are observed and the probabilities of various diseases are assessed. A widely used method of formalizing this approach is independent Bayes in which symptoms are assumed to be independent conditional on the disease category. Correspondence analysis provides a method for examining the dependence between symptoms and assists in the selection of a reduced set of symptoms for the application of the independent Bayes method. This approach is illustrated on two data sets concerned with patients attending Accident and Emergency departments with chest pain and acute abdominal pain, respectively.


Milk Consumption Across Life Periods in Relation to Lower Risk of Nasopharyngeal Carcinoma: A Multicentre Case-Control Study.
Background: The much higher incidence of nasopharyngeal carcinoma (NPC) in men suggests sex hormones as a risk factor, and dairy products contain measurable amounts of steroid hormones. Milk consumption has greatly increased in endemic regions of NPC. We investigated the association between NPC and milk consumption across life periods in Hong Kong. Methods: A multicentre case-control study included 815 histologically confirmed NPC incident cases and 1,502 controls who were frequency-matched on age and sex at five major hospitals in Hong Kong in 2014-2017. Odds ratios (ORs) of NPC (cases vs. controls) for milk consumption at different life periods were estimated by unconditional logistic regression, adjusting for sex, age, socioeconomic status score, smoking and alcohol drinking status, exposure to occupational hazards, family history of cancer, IgA against Epstein-Barr virus viral capsid antigen, and total energy intake. Results: Compared with abstainers, lower risks of NPC were consistently observed in regular users (consuming ≥5 glasses of milk [fresh and powdered combined] per month) across four life periods of age 6-12 (adjusted OR 0.74, 95% CI 0.54-0.86), 13-18 (0.68, 0.55-0.84), 19-30 (0.68, 0.55-0.84), and 10 years before recruitment (0.72, 0.59-0.87). Long-term average milk consumption of ≤2.5, >2.5, and ≤12.5, >12.5 glasses per month yielded adjusted OR (95% CI) of 1.00 (0.80-1.26), 0.98 (0.81-1.18), 0.95 (0.76-1.18), and 0.55 (0.43-0.70), respectively (all P-values for trend < 0.05). Conclusion: Consumption of milk across life periods was associated with lower risks of NPC. If confirmed to be causal, this has important implications for dairy product consumption and prevention of NPC.


Targeting COPZ1 non-oncogene addiction counteracts the viability of thyroid tumor cells.
Thyroid carcinoma is generally associated with good prognosis, but no effective treatments are currently available for aggressive forms not cured by standard therapy. To find novel therapeutic targets for this tumor type, we had previously performed a siRNA-based functional screening to identify genes essential for sustaining the oncogenic phenotype of thyroid tumor cells, but not required to the same extent for the viability of normal cells (non-oncogene addiction paradigm). Among those, we found the coatomer protein complex ζ1 (COPZ1) gene, which is involved in intracellular traffic, autophagy and lipid homeostasis. In this paper, we investigated the mechanisms through which COPZ1 depletion leads to thyroid tumor cell death. We showed that siRNA-mediated COPZ1 depletion causes abortive autophagy, endoplasmic reticulum stress, unfolded protein response and apoptosis. Interestingly, we observed that mouse tumor xenografts, locally treated with siRNA targeting COPZ1, showed a significant reduction of tumor growth. On the whole, we demonstrated for the first time the crucial role of COPZ1 in the viability of thyroid tumor cells, suggesting that it may be considered an attractive target for novel therapeutic approaches for thyroid cancer.


Parental Correlates of Outdoor Play in Boys and Girls Aged 0 to 12-A Systematic Review.
Outdoor play is one major source of physical activity (PA) in children. In particular, parents act as gatekeepers, because they can enable their children's outdoor play. This systematic review aims to provide an overview of parental correlates of outdoor play. A systematic literature research of six electronic databases (ERIC, PsycARTICLES, PsycINFO, PubMed/Medline, SCOPUS, and Web of Science Core Collection) was conducted with previously defined search terms, focusing on children 0⁻12 years old. In total, 1719 potentially publications were screened based on eligibility criteria. Included studies were scored for overall study quality. Findings were summarized using a semi-quantitative method. Twenty-one peer-reviewed publications which examined the relationship of parental correlates and outdoor play were included. Overall, five parental correlates were associated with children's amount of outdoor play: mothers' ethnicity, mothers' employment status, parents' education level, the importance parents assign to outdoor play, and perceived social cohesion in the neighborhood. Merely four studies reported sex/gender-stratified results. In summary, only parents' encouragement/support provided evidence for girls' amount of outdoor play. The findings are considered to be of public health relevance for developing intervention programs to increase outdoor play and for improving child's health. More research, especially considering sex/gender of the child, is required.


Atractyloside induces low contractile reaction of arteriolar smooth muscle through mitochondrial damage.
Atractyloside is the principal naturally occurring active ingredient in ethnomedicines and animal grazing forage. Evidence that atractyloside can induce opening of the mitochondrial permeability transition pore (mPTP) indicates that mitochondrial mechanisms may play an important role in pathophysiological lesions of the heart, liver and kidney after atractyloside poisoning. Therefore, in this study we investigated the association of atractyloside-induced mitochondrial damage in arteriolar smooth muscle cells (ASMCs) with contractile reaction. Atractyloside led to depolarized and swollen or damaged ASMC mitochondria, which might be related to the concentration-dependent induction of mPTP opening. Relative ATP content in ASMCs was significantly reduced by 48%, 63% and 66% of control when cells were treated with 7.5, 10, and 15 µm atractyloside for 10 min, respectively, and ASMCs were hyperpolarized. In addition, the contractile responsiveness of ASMCs was eventually weakened. These results suggest that atractyloside has a toxic effect on vasoreactivity, which is possibly related to mitochondrial damage.


IMPACT OF BARIATRIC SURGERY IN ANXIETY AND ORAL CONDITION OF OBESE INDIVIDUALS: A COHORT PROSPECTIVE STUDY.
Obesity and bariatric surgery may be related with mental and oral disorders. To evaluate the impact of bariatric surgery on anxiety, initial dental caries lesion and gingival bleeding in obese patients. Eighty-nine patients were divided in two groups: Control Group (CG) - obese patients and Experimental Group (EG) - patients submitted to bariatric surgery. EG was analyzed before and 12 months after bariatric surgery; for the CG, was respected an interval of 12 months between the evaluations. International Caries Detection and Assessment System, Gingival Bleeding Index and Trace-State Anxiety Inventory were used. Medical profile, anthropometrics data, sociodemographic and behavioral variables were considered. There were no statistically significant differences between groups in evaluation times regarding to initial dental caries lesion and anxiety. However, the number of teeth with initial dental caries lesion (p=0.0033) and gingival bleeding (p<0.0001) increased significantly after bariatric surgery in EG. These results reinforce the need for multi-professional team follow-up, including dental care, for both obese and bariatric patients.


Social familiarity relaxes the constraints of limited attention and enhances reproduction of group-living predatory mites.
In many group-living animals, within-group associations are determined by familiarity, i.e. familiar individuals, independent of genetic relatedness, preferentially associate with each other. The ultimate causes of this behaviour are poorly understood and rigorous documentation of its adaptive significance is scarce. Limited attention theory states that focusing on a given task has interrelated cognitive, behavioural and physiological costs with respect to the attention paid to other tasks. In multiple signal environments attention has thus to be shared among signals. Assuming that familiar neighbours require less attention than unfamiliar ones, associating with familiar individuals should increase the efficiency in other tasks and ultimately increase fitness. We tested this prediction in adult females of the group-living, plant-inhabiting predatory mite Phytoseiulus persimilis. We evaluated the influence of social familiarity on within-group association behaviour, activity, predation and reproduction. In mixed groups (familiar and unfamiliar), familiar predator females preferentially associated with each other. In pure groups (either familiar or unfamiliar), familiar predator females produced more eggs than unfamiliar females at similar predation rates. Higher egg production was correlated with lower activity levels, indicating decreased restlessness. In light of limited attention theory, we argue that the ability to discriminate between familiar and unfamiliar individuals and preferential association with familiar individuals confers a selective advantage because familiar social environments are cognitively and physiologically less taxing than unfamiliar social environments.


The potential of mesenchymal stem cells to induce immune tolerance to allogeneic transplants.
Organ allograft transplantation is an effective treatment plan for patients with organ failure. Although the application of continuous immunosuppressants makes successful allograft survival possible, the patients' long-term survival rate and quality of life are not ideal. Therefore, it is necessary to find a new strategy to alleviate transplant rejection by developing therapies for permanent allograft acceptance. One promising approach is the application of tolerogenic mesenchymal stem cells (MSCs). Extensive research on MSCs has revealed that MSCs have potent differentiation potential and immunomodulatory properties. This review describes the molecular markers and functional properties of MSCs as well as the immunomodulatory mechanisms of MSCs in transplantation, focuses on the research progress in clinical trials of MSCs, and expounds on the future development prospects and possible limitations.


Lemon extract supported green synthesis of bimetallic CuO/Ag nanoporous materials for sensitive detection of vitamin D3.
In modern era, deficiency of Vitamin D3 is predominantly due to limited exposure to sunlight and UV radiation resulting from indoor lifestyles. Several studies have revealed that vitamin D deficiency can lead to chronic vascular inflammation, diabetes mellitus, hypertension, congestive left ventricular hypertrophy, and heart failure. This study introduces a green synthesis of novel bimetallic nanoporous composite, CuO/Ag using lemon extract. The synthesized nanoporous material, CuO/Ag@lemon extract was characterized using several analytical techniques, including X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). The CuO/Ag@lemon extract nanoparticles were immobilized on glassy carbon electrode (GCE) to prepare modified CuO/Ag@lemon extract-GCE interface. The electrocatalytic and electrochemical properties investigation was carried out on the modified electrode. using cyclic voltammetry (CV), differential pulse voltammetry (DPV), and amperometry for detecting of Vitamin D3. The DPV method displayed a linear response range of 0.02-22.5 µM with a detection limit of 2.62 nM, while the amperometric method showed a broader linear range of 0.25-23.25 µM with a detection limit of 2.70 nM with 82% modified electrode stability. The designed electrode exhibited a positive response to the inclusion of Vitamin D3 with electro-oxidation, reaching steady-state within 3.4 s, with 87% reproducibility within a day. The proposed method offers a rapid and sensitive platform for detection of Vitamin D3 with minimal interference from other molecules. The early diagnosis of Vitamin D3 deficiency using modified electrodes allows for early treatment, thereby preventing severe health complications.


[Molecular mechanisms of apoptosis pathology].
Apoptosis--a programmed cell death--is a general biological mechanism responsible for maintenance of a permanent cell number. Impairment of apoptosis regulation entails disorders in homeostasis and various diseases. This explains biological and medical importance of apoptosis. Molecular grounds of apoptosis regulation, physiological regulation depending on the cell type, examples of apoptosis disregulation leading to definite diseases, approaches to treatment of some diseases basing on knowledge of apoptosis regulation are provided.


Electrophysiological brain activity and memory source monitoring.
To investigate brain mechanisms involved in identifying the origin of memories, event-related potentials (ERPs) were recorded as participants discriminated previously presented (old) from new items or identified their earlier source (picture, word, or new). Differences in ERPs between old-new recognition and source identification were focused at frontal sites. For source identification, prominent negative deflections at occipital or frontal sites occurred depending on encoding task. These results support a model in which memory attributes are distributed neocortically and the frontal lobes are critical for source monitoring.


Radical surgery for ethmoid cancer.
Radical surgery followed by radiotherapy offers the best chance of cure for ethmoid cancer. In operations on 15 patients with ethmoid cancer, intracranial spread was found in five instances. In every patient, a craniofacial ethmoidectomy was performed. Two approaches are recommended. If there is radiologic or clinical evidence of intracranial spread, a frontal craniotomy and lateral rhinotomy approach is employed. With the help of the neurosurgeon, the overlying dura can be resected with the anterior cranial floor. When the cribriform plate appears intact, the resection is accomplished via a lateral rhinotomy and transfrontal sinus approach to the anterior cranial fossa. These techniques were used in 15 patients. Nine are free of recurrence after an observation time of two to seven years.


Antibacterial effects of Alchornea cordifolia (Schumach. and Thonn.) Müll. Arg extracts and compounds on gastrointestinal, skin, respiratory and urinary tract pathogens.
The leaves, stems and roots of Alchornea cordifolia (Schumach. and Thonn.) Müll. Arg. are used as traditional medicine in many African countries for the management of gastrointestinal, respiratory and urinary tract infections as well as for the treatment of wounds. To determine the in vitro antibacterial activity of the crude extracts of leaves and stems of A. cordifolia on gastrointestinal, skin, respiratory and urinary tract pathogens and to identify the compounds in the extracts that may be responsible for this activity. The antibacterial activities of crude extracts [hexane, chloroform (CHCl3), ethyl acetate (EtOAc), ethanol (EtOH), methanol (MeOH) and water (H2O)] as well as pure compounds isolated from these extracts were evaluated by means of the micro-dilution assay against four Gram-positive bacteria, i.e. Bacillus cereus ATCC 11778, Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 25923 and S. saprophyticus ATCC 15305, as well as four Gram-negative bacterial strains, i.e. Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 13883, Moraxella catarrhalis ATCC 23246 and Proteus mirabilis ATCC 43071. The isolation of the active constituents was undertaken by bio-autographic assays in conjunction with chromatographic techniques. The identification and characterisation of the isolated compounds were done using mass spectrometry (MS) and Fourier transformed infrared spectrometry (FTIR) as well as 1D- and 2D- nuclear magnetic resonance (NMR) analyses. The leaves and stems of A. cordifolia exhibited varied antibacterial activity against all eight pathogens. Most of the MIC values ranged between 63 and 2000µg/ml. The highest activities for the crude extracts (63µg/ml) were observed against S. saprophyticus [stem (EtOAc, CHCl3 and hexane), leaves (MeOH, EtOH, EtOAc and CHCl3)], E. coli [stem (MeOH and EtOH), leaves (MeOH, EtOH, EtOAc and CHCl3)], M. catarrhalis [leaves (EtOAc and CHCl3)], K. pneumoniae [stem (CHCl3), leaves (CHCl3)] and S. aureus [leaves (CHCl3)]. Seven constituents [stigmasterol (1), stigmasta-4,22-dien-3-one (2), friedelin (3), friedelane-3-one-28-al (4), 3-O-acetyl-aleuritolic acid (5), 3-O-acetyl-erythrodiol (6) and methyl-3,4,5-trihydroxybenzoate (methyl gallate) (7)] were isolated from the stem MeOH extract. All these compounds displayed some antibacterial activity against the eight pathogens with highest activity against S. saprophyticus (2µg/ml). Furthermore, this is the first report of compounds 1, 2, 3, 4, 6 and 7 isolated from A. cordifolia and where a complete set of 2D-NMR data for fridelane-3-one-28-al (4) is presented. The study demonstrated that the antibacterial activities of A. cordifolia extracts may be due to the presence of the seven isolated compounds, where compounds 3-6 showed the best activity. The observed activity against gastrointestinal, skin, respiratory and urinary tract pathogens supports the traditional use for the treatment of such ailments.


Domain-wall velocities of up to 750 m s(-1) driven by exchange-coupling torque in synthetic antiferromagnets.
The operation of racetrack memories is based on the motion of domain walls in atomically thin, perpendicularly magnetized nanowires, which are interfaced with adjacent metal layers with high spin-orbit coupling. Such domain walls have a chiral Néel structure and can be moved efficiently by electrical currents. High-capacity racetrack memory requires closely packed domain walls, but their density is limited by dipolar coupling from their fringing magnetic fields. These fields can be eliminated using a synthetic antiferromagnetic structure composed of two magnetic sub-layers, exchange-coupled via an ultrathin antiferromagnetic-coupling spacer layer. Here, we show that nanosecond-long current pulses can move domain walls in synthetic antiferromagnetic racetracks that have almost zero net magnetization. The domain walls can be moved even more efficiently and at much higher speeds (up to ∼750 m s(-1)) compared with similar racetracks in which the sub-layers are coupled ferromagnetically. This is due to a stabilization of the Néel domain wall structure, and an exchange coupling torque that is directly proportional to the strength of the antiferromagnetic exchange coupling between the two sub-layers. Moreover, the dependence of the wall velocity on the magnetic field applied along the nanowire is distinct from that of the single-layer racetrack due to the exchange coupling torque. The high domain wall velocities in racetracks that have no net magnetization allow for densely packed yet highly efficient domain-wall-based spintronics.


Abnormal bone marrow findings in patients following treatment with chimeric antigen receptor-T cell therapy.
Bone marrow (BM) assessment after CAR-T cell immunotherapy infusion is not routinely performed to monitor adverse events such as cytopenias, hemophagocytic lymphohistiocytosis, or infections. Our institution has performed BM biopsies as part of CAR-T cell treatment protocols, encompassing pre- and post-treatment time points and during long-term follow-up. We conducted a systematic retrospective review of BM abnormalities observed in samples from 259 patients following CAR-T cell immunotherapy. We correlated BM pathology findings with mortality, relapse/residual disease, and laboratory values. At a median of 35.5 days post-CAR-T infusion, 25.5% showed severe marrow hypocellularity, and 6.2% showed serous atrophy, and peripheral blood cytopenias corroborated these observations. Marrow features associated with reduced disease burden post-CAR-T infusion include increased lymphocytes seen in 16 patients and an increase of macrophages or granulomatous response seen in 25 patients. However, a 100-day landmark analysis also showed increased marrow histiocytes were associated with lower survival (median OS 6.0 vs. 21.4 months, p = .026), as was grade 2-3 marrow reticulin (18 patients) (median OS 12.5 vs. 24.2 months, p = .034). These data represent the first systematic observations of BM changes in patients receiving CAR-T cell immunotherapy.


Use of tablet (iPad®) as a tool for teaching anesthesiology in an orthopedic rotation.
The goal of this study was to compare scores on house staff evaluations of "overall teaching quality" during a rotation in anesthesia for orthopedics in the first six months (n=11 residents were provided with curriculum in a printed binder) and in the final six months (n=9 residents were provided with the same curriculum in a tablet computer (iPad, Apple®, Inc, Cupertino, Ca)). At the beginning of the two-week rotation, the resident was given an iPad containing: a syllabus with daily reading assignments, rotation objectives according to the ACGME core competencies, and journal articles. Prior to the study, these curriculum materials had been distributed in a printed binder. The iPad also provided peer reviewed internet sites and direct access to online textbooks, but was not linked to the electronic medical record. At the end of the rotation, residents anonymously answered questions to evaluate the rotation on an ordinal scale from 1 (unsatisfactory) to 5 (outstanding). All residents were unaware that the data would be analyzed retrospectively for this study. The mean global rating of the rotation as assessed by "overall teaching quality of this rotation" increased from 4.09 (N=11 evaluations before intervention, SD 0.83, median 4, range 3-5) to 4.89 (N=9 evaluations after intervention, SD 0.33, median 5, range 4-5) p=0.04. Residents responded favorably to the introduction of an innovative iPad based curriculum for the orthopedic anesthesia rotation. More studies are needed to show how such mobile computing technologies can enhance learning, especially since residents work at multiple locations, have duty hour limits, and the need to document resident learning in six ACGME core competencies.


[Effects of nitroglycerin and SIN-1 on spontaneous incidence and cGMP levels in the isolated rat atrium].
The effects of nitroglycerin and SIN-1 on atrial rate and intracellular levels of cGMP were studied in the isolated spontaneously beating rat atria. Basal atrial rate was 254 +/- 5 beats X min-1 in the group of experiments performed with SIN-1 and 276 +/- 8 beats X min-1 in that performed with nitroglycerin. No chronotropic effect was detected when nitroglycerin or SIN-1 were added in concentrations ranging from 10(-11)M to 10(-4)M. Measurements of cGMP levels showed that the nucleotide content of atrial tissue increased from a control value of 46.98 +/- 12.1 fmol X mg-1 (w.w.) to 86.4 +/- 3.2 fmol X mg-1 with 10(-5)M SIN-1 and to 107.6 +/- 12.2 fmol X mg-1 with 10(-5)M nitroglycerin (P less than 0.05). The data show no alteration in the chronotropic activity despite the increments in cGMP levels, probably due to an uncoupling between the guanylate cyclase sensitive to SIN-1 and nitroglycerin and the cGMP dependent protein kinase.


Intestinal lymphangiectasia with lipogranulomatous lymphangitis in a dog.
Intestinal lymphangiectasia with lipogranulomatous lymphangitis was diagnosed at necropsy in a 6.5-year-old Maltese dog that had a history of bouts of vomiting, abdominal distention, and diarrhea. The condition was attributed to trauma to the pleural and peritoneal cavities received from bite wounds inflicted one year previously.


Lung cancer. An update.
Lung cancer is the leading cause of cancer mortality in the United States in 1985. Early diagnosis and an aggressive surgical approach offer the best chance for a cure. Unfortunately, the majority of patients will be diagnosed after the disease has metastasized. Radiation therapy and chemotherapy, despite recent advances, are still basically palliative modalities. The most efficacious approach to the control of lung cancer is an effective anti-smoking campaign.


A simple method for construction of pir+ Enterobacterial hosts for maintenance of R6K replicon plasmids.
The R6K replicon is one of the best studied bacterial plasmid replicons. Replication of the R6K plasmid and derivatives harboring its γ origin of replication (ori(R6Kγ)) is dependent on the pir gene-encoded π protein. Originally encoded by R6K, this protein is usually provided in trans in hosts engineered to support replication of plasmids harboring ori(R6Kγ). In Escherichia coli this is commonly achieved by chromosomal integration of pir either via lysogenization with a λpir phage or homologous recombination at a pre-determined locus. Current methods for construction of host strains for ori(R6Kγ)-containing plasmids involve procedures that do not allow selection for presence of the pir gene and require cumbersome and time-consuming screening steps. In this study, we established a mini-Tn7-based method for rapid and reliable construction of pir+ host strains. Using a curable mini-Tn7 delivery plasmid, pir expressing derivatives of several commonly used E. coli cloning and mobilizer strains were isolated using both the wild-type pir+ gene as well as the copy-up pir-116 allele. In addition, we isolated pir+ and pir-116 expressing derivatives of a clinical isolate of Salmonella enterica serovar Typhimurium. In both E. coli and S. enterica serovar Typhimurium, the presence of the pir+ wild-type or pir-116 alleles allowed the replication of ori(R6Kγ)-containing plasmids. A mini-Tn7 system was employed for rapid and reliable engineering of E. coli and S. enterica serovar Typhimurium host strains for plasmids containing ori(R6Kγ). Since mini-Tn7 elements transpose in most, if not all, Gram negative bacteria, we anticipate that with relatively minor modifications this newly established method will for the first time allow engineering of other bacterial species to enable replication of plasmids with ori(R6Kγ).


Single amino acid differences are sufficient for CD4(+) T-cell recognition of a heterologous virus by cattle persistently infected with bovine viral diarrhea virus.
Cattle that are persistently infected (PI) with one strain of bovine viral diarrhea virus (BVDV) can resolve infection with a second, antigenically heterologous strain but not the homologous strain. Since CD4(+) T cells are thought to be critical for the resolution of acute BVDV infection (Howard et al., 1992, Vet. Immunol. Immunopathol. 32, 303-314), we have examined the recognition of a heterologous virus (NADL) by CD4(+) T cells from Pe515-PI animals. The immune response of non-PI control cattle challenged with NADL or Pe515ncp was strain cross-reactive, whereas Pe515-PI animals responded to NADL only. The immune repertoire of both groups included NS3, which differs by approximately 1% (9/683) amino acids between these two viruses. Lymphoproliferative responses to proteins and synthetic peptides corresponding to three nonconservative differences in NS3 demonstrated that CD4(+) T cells from non-PI control animals responded well to proteins but poorly to the peptides from both viruses. In contrast, PI animals were responsive to heterologous proteins and peptides but nonresponsive to the homologous equivalents. A single amino acid difference between the two sequences was sufficient to allow responsiveness.


A longitudinal study of the prevalence and characteristics of breast disorders detected by clinical breast examination during pregnancy and six months postpartum in Ibadan, Southwestern Nigeria.
Breast disorders cause great anxiety for women especially when they occur in pregnancy because breast cancer is the most common cause of cancer related deaths in women. Majority of the disorders are Benign Breast Diseases (BBD) with various degrees of associated breast cancer risks. With increasing breast cancer awareness in Nigeria, we sought to determine the prevalence and characteristics of breast disorders among a cohort of pregnant women. A longitudinal study of 1248 pregnant women recruited in their first trimester- till 26 weeks gestational age consecutively from selected antenatal clinics (ANCs), in Ibadan, Southwest Nigeria. A pretested interviewer- administered questionnaire was used to collect information at recruitment. Clinical Breast Examination (CBE) using MammaCare® technique was performed at recruitment and follow up visits at third trimester, six weeks postpartum and six months postpartum. Women with breast disorders were referred for Breast Ultrasound Scan (BUS) and those with Breast Imaging Reporting and Data System (BIRADS) ≥4 had ultrasound guided biopsy. Statistical analysis was performed using Stata version 14. Mean age of participants was 29.7 ± 5.2 years and mean gestational age at recruitment was 20.4 ± 4.4 weeks. Seventy-two participants (5.8%) had a past history of BBD and 345 (27.6%) were primigravidae. Overall, breast disorder was detected among 223 (17.9%) participants and 149 (11.9%) had it detected at baseline. Findings from the CBE showed that 208 (69.6%) of 299 breast disorders signs found were palpable lumps or thickenings in the breast, 28 (9.4%) were persistent pain, and 63 (21.1%) were abscesses, infection and mastitis. Twenty out of 127 (15.7%) participants who had BUS performed were classified as BIRADS ≥3. Lesions found by BUS were reactive lymph nodes (42.5%), prominent ducts (27.1%), fibroadenoma (9.6%), breast cysts (3.8%) and fibrocystic changes (2.5%). No malignant pathology was found on ultrasound guided biopsy. Breast lump is a major breast disorder among pregnant women attending antenatal clinics in Ibadan. Routine clinical breast examination and follow up of pregnant women found with breast disorders could facilitate early detection of pregnancy associated breast cancer in low resource settings.


Role of (18)F-FDG dual-head gamma-camera coincidence imaging in recurrent or metastatic colorectal carcinoma.
(18)F-FDG PET has been shown to be of high diagnostic accuracy for the evaluation of recurrent colorectal cancer. However, the limited availability of PET scanners precludes (18)F-FDG assessment of many patients for whom the study is indicated. An alternative is the SPECT system in coincidence mode. The aim of this study was to determine the role of dual-head camera (18)F-FDG coincidence imaging (DHC (18)F-FDG) in patients with recurrent colorectal cancer. Sixty-seven DHC (18)F-FDG studies were performed on 62 patients with suspected recurrent colorectal cancer. Reports of contemporary CT were available for the purpose of correlation for 61 of the studies. The final diagnosis of the imaging findings was based on histology or clinical and imaging follow-up of at least 6 mo. In lesion-based analysis, 103 tumor sites were suspected on DHC (18)F-FDG, CT, or colonoscopy. Ninety-three of them were found to be true tumor sites. For DHC (18)F-FDG, the sensitivity was 88%, specificity was 80%, positive predictive value (PPV) was 98%, negative predictive value (NPV) was 42%, and accuracy was 87%. For CT, the sensitivity was 63%, specificity was 10%, PPV was 85%, NPV was 3%, and accuracy was 57%. In patient-based analysis, DHC (18)F-FDG differentiated patients with recurrent cancer from disease-free patients with a sensitivity of 91%, specificity of 73%, PPV of 94%, NPV of 62%, and accuracy of 88%. DHC (18)F-FDG detected tumor sites in 12 (67%) of 18 patients with elevated carcinoembryonic antigen and negative CT findings. DHC (18)F-FDG is an adequate readily available technique for assessment of recurrent colorectal cancer and has a diagnostic accuracy better than that of CT.