Just in time: technology to disseminate curriculum and manage educational requirements with mobile technology.
Learning objectives intended to guide clinical education may be of limited usefulness if they are unavailable to students when interacting with patients. We developed, implemented, and evaluated a Web-based process to disseminate the Clerkship Directors of Internal Medicine curricular objectives to students via handheld computers and for students to upload patient logs to a central database. We delivered this program to all students in our geographically dispersed system, with minimal technological problems. The total number of "hits" on curricular objectives was 8,932 (averaging 149 per student or approximately 2.7 times daily). The average number of "hits" per problem was 470, ranging from 18 for smoking cessation to 1,784 for chest pain. The total number of patient problems logged by students was 9,579, and 91% of students met our prespecified criteria for numbers and types of patients. Dissemination and use of curricular learning objectives and related tools is enhanced with mobile technology.


4-Alkylpiperidines related to SR-48968: potent antagonists of the neurokinin-2 (NK2) receptor.
A series of 4-alkylpiperidine derivatives related to the potent neurokinin-2 (NK2) receptor antagonist SR-48968 (1) is described. Simple aliphatic derivatives were found to be poorly active, but appropriate placement of an alcohol functional group afforded compounds that were of similar activity to 1. Several representatives in this series, such as the 4-(1-hydroxy-1-ethylpropyl)piperidine (14), were found to exhibit oral activity in a model of labored abdominal breathing in guinea pigs. These results expand the latitude of substituents available in this region of this series of NK2 receptor antagonists.


Responses of hepatic and celiac vagal afferents to intraportal mercaptoacetate in rats fed a high-fat or low-fat diet.
Responses of either hepatic or celiac vagal afferents to intraportal hepatic vein administration of 2-mercaptoacetate (MA) were examined in rats maintained on either a high-fat or low-fat diet. Afferent activity in both hepatic and celiac vagal afferents significantly increased after administration of MA, but the magnitude of these increases did not differ as a function of either diet. Responses of hepatic vagal afferents were highly variable across individual rats, whereas those of celiac vagal afferents were remarkably consistent across individual rats. These data suggest that MA-induced enhanced feeding in rats given a fat-enriched diet does not depend on a stronger hepatic and/or celiac vagal afferent response than that of rats given a low-fat diet.


Enhancement of Cunninghamella elegans UCP/WFCC 0542 biomass and chitosan with amino acid supply.
Studies were carried out with Cunninghamella elegans UCP/WFCC 0542 to evaluate the effects of an abundant supply of amino acids, asparagine and corn steep liquor associated with sucrose on the production of biomass and chitosan by submerged fermentation. The concentrations of the components of the culture medium which were determined by a 2³ full factorial design evaluated the interactions and effects of the independent variables of the sucrose, asparagine and corn steep liquor in relation to carbon and nitrogen sources, on the production of chitosan regarding biomass. The best results were observed at the central point [asparagine 0.025%, sucrose 0.15% and 0.45% of corn steep liquor, ratio C:N=2:6], and produced maximum yields of 16.95 g/L biomass and 2.14 g/L chitosan, after 96 h of submerged fermentation. However, the lowest level of sucrose, asparagine and corn steep liquor produced a low amount of biomass (10.83 g/L) and chitosan (0.60 g/L). The infrared spectrum absorption of the chitosan produced by C. elegans showed bands regarding OH-axial stretching between 3406 and 3432 cm⁻¹, superimposed on the NH stretching band with axial deformation of the amide C=O group at about 1639 cm⁻¹, NH angular deformation at approximately 1560 cm⁻¹; axial deformation of amide-CN at around 1421 cm⁻¹, symmetrical angular deformation in CH3 at 1379 cm⁻¹, -CN axial deformation of amino groups from 1125 to 1250 cm⁻¹ and polysaccharide structure bands in the range of between 890-1150 cm⁻¹. The crystallinity index of chitosan was 60.92%, and its degree of deacetylation was 75.25%. A low percentage of a supply of sucrose and asparagine with corn steep liquor offered higher yields of biomass and chitosan production at low cost.


Using the maxillary-nasal angle to evaluate congenital nasal pyriform aperture stenosis.
Congenital nasal pyriform aperture stenosis (CNPAS) is a rare cause of nasal airway obstruction in newborns. The decision to operate is made clinically. Although pyriform aperture width is used for diagnosing CNPAS, it does not fully characterize stenosis of the nasal cavity. To determine the utility of additional metrics for evaluating CNPAS. The medical records of 13 patients with CNPAS treated from 2007 through 2012 at a single tertiary pediatric facility were retrospectively examined. Data on patient demographic characteristics, known genetic abnormalities, and hospital courses were extracted. Computed tomographic images were evaluated for pyriform aperture width; maxillary-nasal angle (MNA), defined as the angle between the anterior maxilla and anterior-posterior nasal axis; and choanal width. Medical management and surgical management. Pyriform aperture width, MNA, and choanal width. Six of 13 patients underwent medical management, and 7 patients underwent surgical treatment. For patients who were managed medically as compared with those managed surgically, the evaluation revealed a larger pyriform aperture width (median [interquartile range {IQR}], 5.6 [5.4-6.1] vs 4.6 [4.5-4.7] mm; P = .03) and MNA (median [IQR], 70° [63°-73°] vs 59° [59°-64°]; P = .048) but no significant difference in choanal width (median [IQR], 11.0 [9.6-12.2] vs 11.9 [10.3-11.9] mm; P = .76). The MNA, when used in conjunction with pyriform aperture width, provides additional pertinent information to supplement clinical decision making in the evaluation of patients with CNPAS. These measurements may be helpful in identifying patients who should undergo surgical intervention, although additional studies would be required to allow predictive use of the MNA.


Trends in television time, non-gaming PC use and moderate-to-vigorous physical activity among German adolescents 2002-2010.
Studies in youth highlight that moderate-to-vigorous physical activity (MVPA) and screen-time behaviours such as television viewing and PC use are associated with a range of health outcomes. However, little is known about recent trends in these behaviours in adolescents. This paper presents time trends in German adolescents' television time, non-gaming PC use as well as MVPA from 2002 to 2010. Data were derived from the cross-sectional German Health Behaviour in School-aged Children (HBSC) study in 2002, 2006 and 2010. Analyses were based on 16,918 11-to 15-year olds boys (49.1%) and girls. Outcome variables were time spent in TV viewing and using a PC (weekday and weekend day) as well as the number of days achieving 60 minutes of MVPA. Changes in both screen-time behaviours and MVPA over time were analysed using sex-specific linear regression, controlling for age and family affluence. TV viewing on weekdays, but not at weekends, declined steadily over time with a difference between 2002 and 2010 of 12.4 min/day in girls and 18.3 min/day in boys (p for trend<.01). We found a strong increase in PC use for non-gaming purposes over time for girls only, with a difference between 2002 and 2010 of 54.1 min/weekday and 68.8 min/weekend day (p<.001). For MVPA we found a slight statistically significant increase in terms of meeting PA guidelines as well as days/week in MVPA for boys and girls (p<.001). In 2010 14.0% of girls and 19.9% of boys met PA guideline. Although MVPA increased from 2002 to 2010 in German adolescents, the time spent in MVPA was still low. Despite the observed decrease in TV viewing, there was no overall decline in the observed screen-based behaviours, especially for girls. This is mainly due to a marked increase in use of a PC for chatting on-line, internet, emailing, homework etc. among girls during the last ten years which outweighs the corresponding decrease in TV viewing. The findings highlight a need for strategies and interventions aimed at reducing screen-time behaviours and promoting MVPA.


Host-pathogen dynamics in longitudinal clinical specimens from patients with COVID-19.
Rapid dissemination of SARS-CoV-2 sequencing data to public repositories has enabled widespread study of viral genomes, but studies of longitudinal specimens from infected persons are relatively limited. Analysis of longitudinal specimens enables understanding of how host immune pressures drive viral evolution in vivo. Here we performed sequencing of 49 longitudinal SARS-CoV-2-positive samples from 20 patients in Washington State collected between March and September of 2020. Viral loads declined over time with an average increase in RT-QPCR cycle threshold of 0.87 per day. We found that there was negligible change in SARS-CoV-2 consensus sequences over time, but identified a number of nonsynonymous variants at low frequencies across the genome. We observed enrichment for a relatively small number of these variants, all of which are now seen in consensus genomes across the globe at low prevalence. In one patient, we saw rapid emergence of various low-level deletion variants at the N-terminal domain of the spike glycoprotein, some of which have previously been shown to be associated with reduced neutralization potency from sera. In a subset of samples that were sequenced using metagenomic methods, differential gene expression analysis showed a downregulation of cytoskeletal genes that was consistent with a loss of ciliated epithelium during infection and recovery. We also identified co-occurrence of bacterial species in samples from multiple hospitalized individuals. These results demonstrate that the intrahost genetic composition of SARS-CoV-2 is dynamic during the course of COVID-19, and highlight the need for continued surveillance and deep sequencing of minor variants.


CXCL16 upregulates RANKL expression in rheumatoid arthritis synovial fibroblasts through the JAK2/STAT3 and p38/MAPK signaling pathway.
To explore the influence of chemokine, CXCL16, on the expression of the receptor activator nuclear factor κB ligand (RANKL) in rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLS). The expression of CXCL16/CXCR6 and RANKL in RA or osteoarthritis (OA) patient synovia was examined by Western blot and immunohistochemistry. The serum concentration of CXCL16 and RANKL was measured by enzyme-linked immunosorbent assay (ELISA). RA-FLS were treated with recombinant CXCL16, and RANKL mRNA and protein were measured using PCR, Western blot and ELISA. The synovial expression of CXCL16, CXCR6, and RANKL was higher in RA patients than in patients with OA. The serum CXCL16 and RANKL levels were higher in RA patients compared with OA patients and healthy controls. CXCL16 correlated with erythrocyte sedimentation rate, C reactive protein, disease activity, serum rheumatoid factor, and RANKL. RA-FLS treated with CXCL16 showed markedly increased expression of RANKL. When STAT3 or p38 activation was blocked by an inhibitor, CXCL16 failed to upregulate RANKL expression. In contrast, inhibiting the Akt or Erk pathway did not achieve the same effect. CXCL16 upregulates RANKL expression in RA-FLS and these effects are mainly mediated by the JAK2/STAT3 and p38/MAPK signaling pathways.


Correction: Inherently chiral calix[4]arenes via oxazoline directed ortholithiation: synthesis and probe of chiral space.
[This corrects the article DOI: 10.3762/bjoc.10.291.].


Induced genetic deficiency of the nucleolar organizer in rat kangaroo cells (PTK1) by ultraviolet laser microirradiation.
An ultraviolet laser microbeam was used to irradiate one of the two nucleolar organizer regions of PTK1 cells in early prophase. The directed nucleolar deficiency induced by ultraviolet laser irradiation was maintained in the daughter cells through subsequent cell generations. However, the frequent occurrence of spontaneous cell fusion in low density cells following the cloning procedure facilitated a recovery of cells to two or more nucleoli.


Technical devices in children with motor disabilities: a review.
To assess the effectiveness of technical devices used in children with motor disabilities. A systematic search of CINAHL Plus, EMBASE, PEDro, Cochrane Library, Isi Web of Knowledge and Scifinder Web was carried out, covering the period between January 2000 and January 2012. The inclusion criteria were: (1) Studies involving a minimum of five children (randomized-clinical trials with control group and experimental group, clinical trials without control group and prospective cohort studies; (2) age range, 0 to 18 years. The methodological quality of the included studies was assessed by the two authors through the application of the PEDro scale. Of the 59 articles identified by the search strategy, 27 articles were considered eligible. The most frequently evaluated devices were ankle and foot orthoses and the most studied pathology was cerebral palsy. The mean score on the PEDro scale was 6.8. The methodological quality of studies needs to be improved and more rigorous research designs should be followed that will allow the effectiveness and quality of movement to be assessed. The satisfaction of the patient and family with the devices should be analyzed in future studies.


Inactivation of the UNC5C Netrin-1 receptor is associated with tumor progression in colorectal malignancies.
The UNC5H netrin-1 receptors (UNC5H1-3 also called UNC5A-C) belong to the functional dependence receptors family, which share the ability to induce apoptosis in the absence of their ligands. Such a trait has been hypothesized to confer a tumor-suppressor activity. Indeed, cells harboring these receptors are thought to be dependent on ligand availability for their survival, thereby inhibiting uncontrolled tumor cell proliferation. We investigate here whether UNC5C acts as a tumor suppressor in colorectal malignancies. The level of UNC5C was analyzed in a panel of 86 primary sporadic colorectal carcinomas. Loss of heterozygosity in the UNC5C locus and epigenetic alterations in the UNC5C promoter were also analyzed. Intestinal tumor progression was monitored in mice bearing both UNC5C and APC1638N mutations, and apoptosis was measured in intestinal tumors developed in UNC5C/APC1638N mutant mice. We show here that UNC5C expression is down-regulated in a large fraction of human colorectal cancers, mainly through promoter methylation. Moreover, in mice, inactivation of UNC5C is associated with increased intestinal tumor progression and a decrease in tumor cell apoptosis. The loss of UNC5C expression observed in human colorectal cancer is a selective advantage for tumor progression, in agreement with the dependence receptor hypothesis. Thus, the UNC5C dependence receptor is a tumor suppressor that regulates sporadic colorectal cancer.


Stopping abuse before it occurs: different solutions for different population groups.
This paper reports on a conference at which participants reviewed indepth the literature on child abuse prevention and child development, as it pertains to different cultural and ethnic population groups, and identifies alternative prevention strategies for these different groups. The efficacy of the following interventions are analyzed: perinatal support programs, education for parents, treatment for abused children, early and periodic childhood screening and treatment programs; social skills training for children and young adults; mutual aid programs and neighborhood support groups; family support services such as crisis care; public information about child abuse and community development activities such as employment assistance. The paper concludes that although treatment services for different groups may be quite similar, prevention strategies must take account of the individual and unique values, norms and socialization patterns of different groups.


Geometric curvature controls the chemical patchiness and self-assembly of nanoparticles.
When organic molecules are tethered onto non-spherical nanoparticles, their chemical properties depend on the particles' local curvature and shape. Based on this observation, we show here that it is possible to engineer chemical patchiness across the surface of a non-spherical nanoparticle using a single chemical species. In particular, when acidic ligands are used, regions of the particle surface with different curvature become charged at different pH values of the surrounding solution. This interplay between particle shape and local electrostatics allows for fine control over nanoscale self-assembly leading to structures with varying degrees of complexity. These structures range from particle cross-stacks to open-lattice crystals, the latter with pore sizes on the order of tens of nanometres, that is, at the lower synthetic limits of metallic mesoporous materials.


The effect of lung deformation on the spatial distribution of pulmonary blood flow.
Pulmonary perfusion measurement using magnetic resonance imaging combined with deformable image registration enabled us to quantify the change in the spatial distribution of pulmonary perfusion at different lung volumes. The current study elucidated the effects of tidal volume lung inflation [functional residual capacity (FRC) + 500 ml and FRC + 1 litre] on the change in pulmonary perfusion distribution. Changes in hydrostatic pressure distribution as well as transmural pressure distribution due to the change in lung height with tidal volume inflation are probably bigger contributors to the redistribution of pulmonary perfusion than the changes in pulmonary vasculature resistance caused by lung tissue stretch. Tidal volume lung inflation results in structural changes in the pulmonary circulation, potentially affecting pulmonary perfusion. We hypothesized that perfusion is recruited to regions receiving the greatest deformation from a tidal breath, thus ensuring ventilation-perfusion matching. Density-normalized perfusion (DNP) magnetic resonance imaging data were obtained in healthy subjects (n = 7) in the right lung at functional residual capacity (FRC), FRC+500 ml, and FRC+1.0 l. Using deformable image registration, the displacement of a sagittal lung slice acquired at FRC to the larger volumes was calculated. Registered DNP images were normalized by the mean to estimate perfusion redistribution (nDNP). Data were evaluated across gravitational regions (dependent, middle, non-dependent) and by lobes (upper, RUL; middle, RML; lower, RLL). Lung inflation did not alter mean DNP within the slice (P = 0.10). The greatest expansion was seen in the dependent region (P < 0.0001: dependent vs non-dependent, P < 0.0001: dependent vs middle) and RLL (P = 0.0015: RLL vs RUL, P < 0.0001: RLL vs RML). Neither nDNP recruitment to RLL [+500 ml = -0.047(0.145), +1 litre = 0.018(0.096)] nor to dependent lung [+500 ml = -0.058(0.126), +1 litre = -0.023(0.106)] were found. Instead, redistribution was seen in decreased nDNP in the non-dependent [+500 ml = -0.075(0.152), +1 litre = -0.137(0.167)) and increased nDNP in the gravitational middle lung [+500 ml = 0.098(0.058), +1 litre = 0.093(0.081)] (P = 0.01). However, there was no significant lobar redistribution (P < 0.89). Contrary to our hypothesis, based on the comparison between gravitational and lobar perfusion data, perfusion was not redistributed to the regions of the most inflation. This suggests that either changes in hydrostatic pressure or transmural pressure distribution in the gravitational direction are implicated in the redistribution of perfusion away from the non-dependent lung.


The predictive value of laboratory findings in patients with primary hyperparathyroidism.
Despite extensive preoperative imaging and intraoperative "gadgetry" to facilitate localization of abnormal parathyroid glands, the onus of identification and resection remains with the surgeon in the operating room. We pondered the relative usefulness of routine laboratory studies to the surgeon as predictive guides to the intraoperative findings in patients with primary hyperparathyroidism (HPT). Pre- and postoperative laboratory data were analyzed in 166 consecutive patients (1998 to 1999) undergoing successful cervical exploration for sporadic primary HPT and were correlated with the pathologic findings. Patients with secondary HPT, multiple endocrine neoplasia, familial HPT, and parathyroid carcinoma were not included in this study. One hundred eighteen women and 48 men (mean age = 63 years) with parathyroid adenoma (n = 155) and sporadic hyperplasia (n = 11) were evaluated. Mean parathormone (PTH) levels varied little with the pathology: adenoma = 9.6 pmol/L and hyperplasia = 10.2 pmol/L (p > 0.05). In patients with parathyroid adenoma, analysis of preoperative measures showed a positive correlation (r = 0.48, p < 0.0001) with PTH and gland weight. The correlation appeared to be the strongest in the tails of the distribution; in 22 of 23 (96%) cases with PTH levels lower than 6 pmol/L, the offending lesion or lesions were less than 400 mg; in all six cases with PTH levels higher than 18.0 pmol/L, the abnormal gland or glands weighed more than 800 mg. PTH levels between 6 and 18 pmol/L revealed mean adenoma weight of 757 mg (median = 420 mg; range = 50 to 5,500 mg). Extreme values of PTH in patients with single-gland parathyroid disease alert the surgeon to the likelihood of small or large parathyroid adenomas. Laboratory studies do not differentiate adenoma from hyperplasia, nor do they pinpoint the size of abnormal glands with moderate-range PTH values.


Pattern of distribution of 35 red cell antigens in regular voluntary blood donors of South Gujarat, India.
Extended phenotyping is one of the important method of reducing red cell alloimmunisation. Extended phenotyping of red cells from voluntary donors have many uses in addition to its application in population genetics. As there was very little data extended phenotyping on a cohort of Indian Voluntary blood donors this project was undertaken. 200 regular voluntary blood donors having 'O' blood group were included for red cell antigen typing of Rh (D,C,E,c,e), Kell (K, k, Kpa, Kpb), Duffy (Fya, Fyb), Kidd (Jka, Jkb), Lewis(Lea, Leb), P(P1), MNS (M, N,S,s), and Lutheran (Lua, Lub), Colton (Coa, Cob), Diago (Diaa, Wra), Vw and Xga antigens using conventional antisera provided by DIAGAST. Calculations of antigen and phenotypes frequencies were expressed as percentages. Out of 200 'O' group blood donors, 96.5% were Rh D and 2.5% were K positive. Amongst Rh antigens, e was the most common (100%) followed by D, C (91.0%), c (50.5%) and E (16.5%) with DCe/DCe (R1R1, 48.0%) being the most common phenotype. In Kell blood group system, we found k antigen to be 100% and a rare phenotype Kp (a + b+) was found in 1% of the donors. For Kidd and Duffy blood group systems, Jk (a + b+) and Fy (a + b-) were the most common phenotypes (39.0% and 64.0%, respectively). In the MNS blood group system, M + N+ (67.5%) and S + s+(43.5%) were the most common phenotypes. There were antigens like Cw(3.5%), K(2.3%), Kpa(1.2%), Ina(1.0%), Vw(1.2%), Coa(4.5%), Cob(1%), Lua(1.75%), Dia+(1.2%), and Wra+(0.6%) with frequency < 5% in the donor population. Extensively antigen phenotypes group 'O' red cells showed significant variation with other population from India as well as with Caucasian and black population. Extensive phenotyping 'O' group regular blood donors of red cell antigens is very useful to prepare in-house red cell panels for identification of alloantibodies.


Uptake of 6-fluoro-5-hydroxytryptamine and 4,6-difluoro-5-hydroxytryptamine into releasable and non-releasable compartments of human platelets.
1 The ring-fluorinated compounds, 6-fluoro-5-hydroxytryptamine and 4,6-difluoro-5-hydroxytryptamine, are sterically similar to 5-hydroxytryptamine (5-HT) but have pKaS for their 5-hydroxyl groups (9.7 and 8.0 respectively) which are lower than that of 5-HT. 2 The rates at which [3H]-5-HT, [3H]-6-fluoro-5-HT, and [3H]-4,6-difluoro-5-HT entered the releasable (vesicular) and non-releasable compartments of washed human platelets during a 1 min incubation period at 37 degrees C were similar. These portions of the uptake process therefore appears to be relatively independent of the pKa of the 5-hydroxyl group. 3 The [3H]-4,6-difluoro-5-HT was unique since material accumulated in the non-releasable compartment during uptake did not migrate into the vesicular compartment under appropriate incubation conditions. 4 The data suggest that the zwitterionic form of 5-HT is not the transported species, but that the electronic configuration about the 5-hydroxyl group may be critical for translocation from a non-releasable to a releasable compartment.


Quantitative dynamic contrast-enhanced parameters and intravoxel incoherent motion facilitate the prediction of TP53 status and risk stratification of early-stage endometrial carcinoma.
The aim of the study was to investigate the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and intravoxel incoherent motion (IVIM) in differentiating TP53-mutant from wild type, low-risk from non-low-risk early-stage endometrial carcinoma (EC). A total of 74 EC patients underwent pelvic MRI. Parameters volume transfer constant (Ktrans), rate transfer constant (Kep), the volume of extravascular extracellular space per unit volume of tissue (Ve), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and microvascular volume fraction (f) were compared. The combination of parameters was investigated by logistic regression and evaluated by bootstrap (1000 samples), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). In the TP53-mutant group, Ktrans and Kep were higher and D was lower than in the TP53-wild group; Ktrans, Ve, f, and D were lower in the non-low-risk group than in the low-risk group (all P < 0.05). In the identification of TP53-mutant and TP53-wild early-stage EC, Ktrans and D were independent predictors, and the combination of them had an optimal diagnostic efficacy (AUC, 0.867; sensitivity, 92.00%; specificity, 80.95%), which was significantly better than D (Z = 2.169, P = 0.030) and Ktrans (Z = 2.572, P = 0.010). In the identification of low-risk and non-low-risk early-stage EC, Ktrans, Ve, and f were independent predictors, and the combination of them had an optimal diagnostic efficacy (AUC, 0.947; sensitivity, 83.33%; specificity, 93.18%), which was significantly better than D (Z = 3.113, P = 0.002), f (Z = 4.317, P < 0.001), Ktrans (Z = 2.713, P = 0.007), and Ve (Z = 3.175, P = 0.002). The calibration curves showed that the above two combinations of independent predictors, both have good consistency, and DCA showed that these combinations were reliable clinical prediction tools. Both DCE-MRI and IVIM facilitate the prediction of TP53 status and risk stratification in early-stage EC. Compare with each single parameter, the combination of independent predictors provided better predictive power and may serve as a superior imaging marker.


Water quality criteria of total ammonia nitrogen (TAN) and un-ionized ammonia (NH3-N) and their ecological risk in the Liao River, China.
Ammonia has drawn great concern worldwide due to its ubiquity in surface water and high toxic effect. In China, ammonia pollution issues in the Liao River were highlighted from the Ministry of Ecology and Environment annual report. In this study, water quality criteria (WQC) for two types of ammonia (total ammonia nitrogen (TAN) and un-ionized ammonia (NH3-N)) and related temporal concentration distributions and ecological risks in the Liao River were investigated. For sampling sites (2014) and national monitoring sites (2008, 2013, 2016, 2017 and 2018) of the Liao River, there were seasonal variations identified for TAN and NH3-N. More specifically, high concentrations of TAN and NH3-N occurred separately in winter and summer, and there were increasing trends for TAN and NH3-N from 2013 to 2018. The acute and chronic WQC values for TAN based on the toxicity values of the Liao River species were 16.86 and 4.39 mg/L (pH of 7.0 and temperature of 20 °C), and the acute and chronic WQC values for NH3-N were 0.067 and 0.017 mg/L. The exceedance probabilities of 5% species affected for long-term exposure of TAN and NH3-N were ≥30% in 2014. In addition, the increasing trend of concentrations and ecological risks posed by NH3-N from 2013 should be paying more attention. This study could provide useful information for ammonia environmental risk management in China and ecological risk assessment procedure for NH3-N and TAN exposure in similar surface waters worldwide.


Four-year data after pediatric renal transplantation: a randomized trial of tacrolimus vs. cyclosporin microemulsion.
This study was undertaken to compare the efficacy and safety of tacrolimus (Tac) with cyclosporin microemulsion (CyA) in pediatric renal recipients. A 6-month, randomized, prospective, open, parallel group study with an open extension phase was conducted in 18 centers from nine European countries. In total, 196 pediatric patients (<18 yr) were randomly assigned (1:1) to receive either Tac (n = 103) or CyA (n = 93) administered concomitantly with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection (intent-to-treat). Baseline characteristics were comparable between treatment groups. Excluding deceased patients (n = 9) and patients lost to follow-up (n = 31, mostly transferred to adult care), 95% of 2-yr data (159 of 167 possible patients), 87% of 3-yr data (142 of 163) and 73% of 4-yr data (114 of 156) were retrieved. At 1 yr Tac therapy resulted in a significantly lower incidence of acute rejection (36.9%) compared with CyA (59.1%, p = 0.003). The incidence of corticosteroid-resistant rejection was also significantly lower with Tac (7.8% vs. 25.8%, p = 0.001). At 4 yr, patient survival was similar (94% vs. 92%, p = 0.86) but graft survival significantly favored Tac (86% vs. 69%; p = 0.025, log-rank test), respectively. At 1 yr, the mean glomerular filtration rate (GFR) (Schwartz formula, ml/min/1.73 m(2)) was 64.9 +/- 20.7 (n = 84) vs. 57.8 +/- 21.9 (n = 77, p = 0.0355), at 2 yr 64.9 +/- 19.8 (n = 71) vs. 51.7 +/- 20.3 (n = 66, p = 0.0002), at 3 yr 66.7 +/- 26.4 (n = 81) vs. 53.0 +/- 23.3 (n = 55, p = 0.0022), and at 4 yr 71.5 +/- 22.9 (n = 51) vs. 53.0 +/- 21.6 (n = 44, p = 0.0001) for Tac vs. CyA, respectively. Cholesterol remained significantly higher with CyA throughout follow-up. Three patients in each arm developed post-transplant lymphoproliferative disease. Incidence of insulin-dependent diabetes mellitus was not different. Tac was significantly more effective than CyA in preventing acute rejection in pediatric renal recipients. Renal function and graft survival were also superior with Tac. Glomerular filtration rate appears to be an useful surrogate marker for long-term outcome.


A novel switchable-hydrophilicity, natural deep eutectic solvent (NaDES)-based system for bio-safe biorefinery.
A switchable-hydrophilicity solvent system, consisting of a fatty acid-based natural deep eutectic solvent (NaDES), complemented by a bio-friendly dilute amine solution, has been introduced. The potential of the most benign switchable solvent system has been characterised in microalgae biorefining according to the recently proposed 'Circular Extraction' scheme.


Free cytoplasmic messenger ribonucleoprotein complexes from rabbit reticulocytes.
Free cytoplasmic globin mRNA containing mRNP-particles were isolated from rabbit reticulocytes by zonal sucrose gradient centrifugation and their properties were compared with mRNP particles isolated in the same way from EDTA-dissociated reticulocyte polyribosomes. The average poly(A)-length of 9S mRNA from free cytoplasmic mRNP was 17-20 nucleotides being about two times shorter than the average poly(A)-length of polysomal 9S mRNA. The protein composition of the free cytoplasmic mRNP particles disclosed the absence of the 76,000 dalton protein which is associated with the 3'poly(A)-segment of polysomal globin mRNA. It was concluded that free cytoplasmic mRNP-particles from rabbit reticulocytes can be classified as "old" mRNP in a post-translational phase. Free cytoplasmic mRNPs were translated in heterologous cell-free systems as well as in Xenopus laevis oocytes. Addition of hemin stimulated the synthesis of alpha-globin in all systems, while the presence of the cap analogue m7G(5')p inhibited translation of free cytoplasmic mRNA completely. The latter finding suggested that free cytoplasmic mRNA has a 5' terminal "cap". Shortening of the poly(A)-segment with concomitant loss of the 76,000 dalton protein may lead to less efficient translation of free cytoplasmic mRNP.


Evidence for metabotropic function of epithelial nicotinic cholinergic receptors in rat colon.
ACh exerts its actions via nicotinic (nAChR) and muscarinic receptors. In the peripheral nervous system, ionotropic nAChR mediate responses in excitable cells. However, recent studies demonstrate the expression of nAChR in the colonic epithelium, which are coupled to an induction of Cl- secretion via activation of the Na+ -K+ -pump. In order to find out whether these epithelial nAChR function as ionotropic receptors, intracellular microelectrode and imaging experiments were performed in isolated crypts from rat colon. Apically permeabilized epithelia were used to measure pump current across the basolateral membrane. Imaging experiments with the Na+ -sensitive dye SBFI revealed that nicotine induced a decrease in the cytosolic Na+ concentration concomitant with a fall in the cytosolic Ca2+ concentration in about 50% of the cells. as shown in fura-2 experiments. Nicotine hyperpolarized the membrane by 6.4 ± 2.1 mV. These observations contradict the assumption that epithelial nAChR function as ligand-gated non-selective cation channels. The decrease in the cytosolic Na+ concentration was strongly delayed, when the Na+ -K+ -pump was inhibited by scilliroside. Ussing chamber experiments revealed a strong dependence of the nicotine-induced pump current on the presence of Ca2+ , and chelation of cytosolic Ca2+ with BAPTA prevented the fall in the cytosolic Na+ concentration in SBFI-loaded crypts. Inhibition of PKC with GF 109203X or Goe 6983 significantly reduced the nicotine-induced pump current. These results suggest that epithelial nAChR activate the Na+ -K+ -pump via a PKC dependent on a sufficient cytosolic Ca2+ concentration.


Bernardino Ramazzini's early observations of the link between musculoskeletal disorders and ergonomic factors.
Bernardino Ramazzini (1633-1714) systematically studied the relationship between work and diseases. He realized that it was not possible to ascribe all workers' diseases to chemicals or physical agents and foresaw that other factors were involved. He observed that common diseases could originate following the maintenance either of prolonged stationary postures or of unnatural postures (e.g. bakers, workers who stand, sedentary worker, scribes, weavers) or following activities requiring heavy muscular performance (e.g. porters and woodworkers). Furthermore, Ramazzini recognized the need to undertake measures to prevent disorders from repetitive motions and manual lifting and anticipated the now accepted advice of moderation and recommendations of reduction of work duration for a number of hard jobs requiring a standing position or severe muscular effort. From his early writings therefore it is evident that Ramazzini realized the importance of assessing the ergonomic factors associated with the occurrence of work-related musculoskeletal disorders.


Season-dependent effects of ZnO nanoparticles and elevated temperature on bioenergetics of the blue mussel Mytilus edulis.
Input of ZnO nanoparticles (nZnO) from multiple sources have raised concerns about the potential toxic effects on estuarine and coastal organisms. The toxicity of nZnO and its interaction with common abiotic stressors (such as elevated temperature) are not well understood in these organisms. Here, we examined the bioenergetics responses of the blue mussel Mytilus edulis exposed for 21 days to different concentrations of nZnO or dissolved zinc (Zn2+) (0, 10, 100 μg l-1) and two temperatures (ambient and 5 °C warmer) in winter and summer. Exposure to nZnO had little effect on the protein and lipid levels, but led to a significant depletion of carbohydrates and a decrease in the electron transport system (ETS) activity. Qualitatively similar but weaker effects were found for dissolved Zn. In winter mussels, elevated temperature (15 °C) led to elevated protein and lipid levels increasing the total energy content of the tissues. In contrast, elevated temperature (20 °C) resulted in a decrease in the lipid and carbohydrate levels and suppressed ETS in summer mussels. These data indicate that moderate warming in winter (but not in summer) might partially compensate for the bioenergetics stress caused by nZnO toxicity in M. edulis from temperate areas such as the Baltic Sea.


Diabetes associated with cervical carcinoma among high-risk HPV-infected patients with cytologically diagnosed high grade squamous intraepithelial lesion.
Diabetes causes metabolic disorders and immune changes that may be potential triggers of cervical cancer. Therefore, diabetes is not a "bystander" to cervical cancer. However, the conclusion that diabetes promotes cervical cancer lacks clinical epidemiological evidence, and the reported potential association between diabetes and cervical cancer is controversial. We conducted an explorative cross-sectional study of 791 women with cytological HGSIL and HR-HPV, who attended the cervical clinic of the largest academic women's hospital in China from May 2019 to March 2022. After cervical screening, patients who were requiring colposcopy were tested for HbA1c. HbA1c level of 6.5% or higher defines diabetes and HbA1c level of 5.7%-6.4% was defined as prediabetes. The relationship between diabetes and cervical cancer was observed by a dose-response graph. Subgroup analysis and multivariate logistic regression analysis were conducted to estimate the associations between diabetes and cervical cancer. Among HGSIL patients with high-risk HPV infection, compared with women with HbA1c <5.7%, the odds ratio for women with prediabetes was 1.72 (95% CI: 0.87-3.41) and the odds ratio for women with diabetes was 3.29 (95% CI: 1.10-9.80) for cervical cancer. Sensitivity analysis showed that diabetes was significantly associated with cervical cancer in different age groups and different HPV variant. E-value analysis showed robustness to unmeasured confounding. In patients with HR-HPV combined with HGSIL, diabetes and prediabetes are associated with cervical cancer.


Effects of vasoactive intestinal peptide and other peptides on cyclic AMP accumulation in intact pieces and isolated horizontal cells of the teleost retina.
The effects of vasoactive intestinal peptide (VIP) and several other peptides have been examined on cyclic AMP accumulation in intact pieces and isolated horizontal cells of the teleost (carp) retina. VIP was the most effective peptide examined, inducing a dose-related response, and an approximately fivefold increase in cyclic AMP production when used at a concentration of 10 microM. Porcine histidine isoleucine-containing peptide and secretin, peptides structurally related to VIP, also stimulated cyclic AMP accumulation, but at concentrations of 10 microM induced responses which were only approximately 40% and 10%, respectively, of the response observed with 10 microM VIP. In contrast, several other peptides, including glucagon, neurotensin, somatostatin, luteinizing hormone-releasing hormone, alpha-melanocyte-stimulating hormone, cholecystokinin octapeptide26-33, gastrin-releasing peptide, thyrotropin-releasing hormone, and VIP10-28 were totally inactive. The response to 10 microM VIP was not antagonized by several dopamine antagonists, indicating the presence of a population of specific VIP receptors coupled to adenylate cyclase, distinct from the population of dopamine receptors coupled to adenylate cyclase also known to be present in this tissue. Finally, experiments involving the use of fractions of isolated horizontal cells indicate that these neurons possess a population of VIP receptors coupled to cyclic AMP production which would appear to share a common pool of adenylate cyclase with a population of similarly coupled dopamine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)


Cognitive requirements of cumulative culture: teaching is useful but not essential.
The cumulative nature of human culture is unique in the animal kingdom. Progressive improvements in tools and technologies have facilitated humanity's spread across the globe and shaped human evolution, but the cognitive mechanisms enabling cultural change remain unclear. Here we show that, contrary to theoretical predictions, cumulative improvements in tools are not dependent on specialised, high-fidelity social learning mechanisms. Participants were tasked with building a basket to carry as much rice as possible using a set of everyday materials and divided into treatment groups with differing opportunities to learn asocially, imitate, receive teaching or emulate by examining baskets made by previous chain members. Teaching chains produced more robust baskets, but neither teaching nor imitation were strictly necessary for cumulative improvements; emulation chains generated equivalent increases in efficacy despite exhibiting relatively low copying fidelity. People used social information strategically, choosing different materials to make their baskets if the previous basket in the chain performed poorly. Together, these results suggest that cumulative culture does not rest on high-fidelity social learning mechanisms alone. Instead, the roots of human cultural prowess may lie in the interplay of strategic social learning with other cognitive traits including the ability to reverse engineer artefacts through causal reasoning.


Robotic cholecystectomy: training of residents in use of the robotic platform.
The expanding use of robotic technology has introduced a requirement to incorporate this technology into traditional training programs. The goal of this study is to demonstrate the safe introduction of the robotic surgical system during residency programs, using robotic cholecystectomy as the basic procedure. A total of 170 patients who underwent robotic cholecystectomy at a tertiary center were retrospectively reviewed. Data collected included patient's age, gender, weight, BMI, operative time, hospital stay, associated procedures, and complications. Of the 170 patients, mean age, BMI, operative time and estimated blood loss was 40.04 years, 32.78 kg/m(2) , 93.79 minutes and 13.67 mL, respectively, with acceptable complications. Within the context of a traditional residency program, a standardized training curriculum and technique can be applied to educate residents without increasing surgical complication in the use of robotic platform. Robotic cholecystectomy is a safe and appropriate basic procedure to provide this training.


Auditory neural activity evoked by pure-tone stimulation as a function of intensity.
The 2-deoxyglucose (2-DG) autoradiographic technique was employed to map activation of the central auditory pathway in the mongolian gerbil during stimulation with a 3.0 kHz tone at several intensities. In most auditory nuclei, the tone produced restricted areas in which 2-DG uptake was markedly higher than that of adjacent tissue, at locations consistent with the known tonotopic organization of the structure. The size of these regions changed relatively little with increasing stimulus intensity from 25 to 65 dB SPL (re 0.0002 dyne/cm2). At higher intensities, evoked uptake spreads into locations which represent frequencies above 3.0 kHz. In the inferior colliculus, relative 2-DG uptake decreased with increasing stimulus intensity in bands on either side of the 3.0 kHz region. These bands of reduced uptake became wider with increasing stimulus intensity from 25 to 85 dB SPL. The optical densities of auditory structures were normalized by the density of non-auditory white matter to derive optical density ratios. In the cochlear nuclei, optical density ratios in the 3.0 kHz region increased monotonically with increasing stimulus intensity, to a plateau at 45 dB SPL. In higher auditory nuclei, relative 2-DG uptake increased to a peak at 45 dB SPL and then declined at higher intensities.


Mid-Victorian science museums and exhibitions: 'the industrial amusement and instruction of the people'.
The Royal Polytechnic Institution, Wyld's Globe and the Royal Panopticon were part of a family of institutions that existed in the post-Great Exhibition era that shared a common approach to popularizing science based on the blending of education and entertainment. Studying them helps us to understand the Victorian fascination with science, especially in the third quarter of the century. It draws our attention to the important role of popularizers of science who worked in these museums and exhibitions. Once their role is added to our account of the cult of science, a very different picture emerges that forces us to reconsider the standard story of the dominance of the scientific scene in the second half of the century by figures such as Darwin, Huxley and Tyndall.


Multisite proteins and randomly coiled polymeric ligands. Chain length dependence of binding constants.
A model mechanism was developed for the binding of a rigid multisite protein with a randomly coiled multivalent ligand. Probabilities of the formation of chain loops between sites located at given distances at the protein were calculated by an extension of the concept of ring closure in coiled chain molecules. Expressions were derived for the dependence of overall equilibrium quantities, such as the binding constant between the protein and the ligand, on intrinsic parameters such as intrinsic binding constants, number of sites at the protein and their distances and on the chain length of the polymeric ligand. A pronounced chain length dependence of the overall binding constant was predicted even at chain lengths much longer than the size of the protein. Such a dependence was previously observed for the enzyme prolyl hydroxylase which acts on polymeric substrates like (ProProGly)n. This so far unexplained feature is quantitatively described by the model mechanism which is believed to be applicable to many other interactions of biological importance.


A novel homozygous p.Arg527Leu LMNA mutation in two unrelated Egyptian families causes overlapping mandibuloacral dysplasia and progeria syndrome.
Mandibuloacral dysplasia (MAD) is a rare disease resulting from a mutation of LMNA gene encoding lamins A and C. The most common mutation associated with this disease is a homozygous arginine 527 replacement by histidine. Three female patients originating from two unrelated families from Northeast Egypt were examined. Their growth was retarded; they had microcephaly, widened cranial sutures, prominent eyes and cheeks, micrognathia, dental crowding, hypoplastic mandible, acro-osteolysis of distal phalanges, and joint contractures. In addition, they presented some progeroid features, such as pinched nose, premature loss of teeth, loss of hair, scleroderma-like skin atrophy, spine rigidity, and waddling gait. The clinical presentation of the disease varied between the patient originating from Family 1 and patients from Family 2, suggesting that unknown, possibly epigenetic factors, modify the course of the disease. The first symptoms of the disease appeared at the age of 2.5 (a girl from Family 1), 5, and 3 years (girls from Family 2). All patients had the same, novel homozygous c.1580G>T LMNA mutation, resulting in the replacement of arginine 527 by leucine. Computational predictions of such substitution effects suggested that it might alter protein stability and increase the tendency for protein aggregation, and as a result, might influence its interaction with other proteins. In addition, restriction fragment-length polymorphism analysis performed in 178 unrelated individuals showed that up to 1.12% of inhabitants of Northeast Egypt might be heterozygous carriers of this mutation, suggesting the presence of a founder effect in this area.


All-small-molecule supramolecular hydrogels assembled from guanosine 5'-monophosphate disodium salt and tobramycin for the treatment of bacterial keratitis.
Bacterial keratitis is the most common corneal infection which may lead to blindness, and seriously threatened the human visual health worldwide. Clinical treatment with antibiotic eye drops formulation usually falls in low bioavailability and poor therapeutic efficiency. Hydrogel has gained much attention as ophthalmic formulation recently due to the prolonged drug retention on ocular surface. In this study, we proposed a type of all-small-molecule supramolecular hydrogel assembled from guanosine-5'-monophosphate disodium salt and tobramycin for the treatment of bacterial keratitis. Guanosine-5'-monophosphate disodium salt assembled into guanosine-quartet nanofibers via hydrogen bonding and π-π stacking, and tobramycin with five primary amine groups further crosslinked the nanofibers bearing multiple phosphate moieties into gel networks via ionic interactions. The supramolecular gel showed shear thinning and thixotropic properties, good biocompatibility, and antibacterial activity. The gel treatment significantly ameliorated P. aeruginosa induced bacterial keratitis, and showed higher therapeutic efficacy compared to tobramycin eye drop. This study provides a facile and efficient antibiotic gel formulation for clinical treatment of bacterial keratitis.


Dysgenetic male pseudohermaphroditism.
Dysgenetic male pseudohermaphroditism is a disorder of sexual differentiation in which patients present with bilateral dysgenetic testes, persistent müllerian structures, cryptorchidism and inadequate virilization. There were 10 patients with this syndrome seen at our hospital between 1956 and 1976. In this series, there was a 30 per cent incidence of testicular tumors. Because patients with dysgenetic male pseudohermaphroditism have a high incidence of testicular tumors this disorder, which is actually a variant of mixed gonadal dysgenesis, must be distinguished from the other forms of male pseudohermaphroditism.


One-stage reconstruction of the antihelix and concha using postauricular island flap.
Tissue defects in the antihelix and the concha due to oncological resection and trauma can be successfully repaired with a subcutaneously based postauricular island flap. Alternative methods of regional reconstruction usually need two stages or may require grafts in some patients. We present the one-stage technique, as described by Masson, without grafts, to provide adequate reconstruction and aesthetic restoration of the area, illustrated by 62 patients. In all patients there has been a follow-up period of 12 months. This report provides evidence for the aesthetic superiority of this method. An excellent aesthetic outcome was achieved in 46 patients, an adequate outcome in 15 patients, and a poor result in only 1 patient. No flap necrosis was observed. The method has considerable advantages for the repair of anterior conchal and antihelical defects.


Circadian plasma cortisol levels during topical use of desoximetasone and triamcinolone acetonide in man.
The effect of topical use of desoximetasone (Topisolon ointment) and triamcinolone acetonide (Volon A cream) for 3 to 4 days on circadian plasma cortisol levels was studied in 22 hospitalized patients (mean age 61 years) for Topisolon, and in ten patients (mean age 59 years) for Volon A. The differences in cortisol levels (RIA) were examined by the frequency distribution analysis of Daeves and Beckel (1958). The need to analyze the features of the distribution curves was clearly demonstrated in preference to simple averaging statistics which rely upon the arithmetic mean as the main parameter. The results suggest two distinct groups of morning plasma cortisol levels - one at a low level of 5.6 X 1.85 +/- 1 and one at a high level of 15.4 X 1.56 +/- 1 microgram/100 ml. The evening level was uniform 6.5 X 2.13 +/- 1 microgram/100 ml. Topisolon depressed the plasma cortisol levels in all groups. Volon A seemed to reduce only the morning high level group to lower values. In addition, Topisolon altered the proportions of patients with high and low plasma cortisol levels, while Volon A had little effect. The different responses of the plasma cortisol levels may imply different kinetics of cutaneous penetration and cutaneous metabolism of the two synthetic corticosteroids.


The effect of methocarbamol and mexiletine on murine muscle spindle function.
The muscle relaxant methocarbamol and the antimyotonic drug mexiletine are widely used for the treatment of muscle spasms, myotonia, and pain syndromes. To determine whether these drugs affect muscle spindle function, we studied their effect on the resting discharge and on stretch-induced action potential frequencies of proprioceptive afferent neurons. Single unit action potential frequencies of proprioceptive afferents from muscle spindles in the murine extensor digitorum longus muscle of adult C57BL/6J mice were recorded under resting conditions and during ramp-and-hold stretches. Maximal tetanic force of the same muscle after direct stimulation was determined. High-resolution confocal microscopy analysis was performed to determine the distribution of Nav 1.4 channels, a potential target for both drugs. Methocarbamol and mexiletine inhibited the muscle spindle resting discharge in a dose-dependent manner with IC50 values around 300 μM and 6 μM, respectively. With increasing concentrations of both drugs, the response to stretch was also affected, with the static sensitivity first followed by the dynamic sensitivity. At high concentrations, both drugs completely blocked muscle spindle afferent output. Both drugs also reversibly reduced the specific force of the extensor digitorum longus muscle after tetanic stimulation. Finally, we present evidence for the presence and specific localization of the voltage-gated sodium channel Nav 1.4 in intrafusal fibers. In this study we demonstrate that both muscle relaxants affect muscle spindle function, suggesting impaired proprioception as a potential side effect of both drugs. Moreover, our results provide additional evidence of a peripheral activity of methocarbamol and mexiletine.


Eicosanoid production and transfer in the placenta of the diabetic pregnancy.
The metabolism of arachidonic acid (AA) and the transfer of its metabolites was determined in in vitro perfused placental tissue from normal pregnancies and those complicated by maternal insulin-dependent diabetes mellitus (IDDM). 14C-labelled AA was recirculated in the fetal circulation for 60 min while 3H-AA was recirculated in the maternal circulation. Placental effluent was subjected to high performance liquid chromatography (HPLC) and analysis of dual-label scintillation counts. Placentae from IDDM pregnancies converted 3-6 times more radiolabelled AA to eicosanoids than did normal placentae. In addition, the transfer of eicosanoids into the opposing circulation was doubled in placentae from IDDM pregnancies compared to normal placentae. The predominant direction of eicosanoid transfer in both groups of placentae was in the fetal-to-maternal direction. The relative amounts of eicosanoids produced was also altered in placentae from IDDM pregnancies. Increased amounts of thromboxane (Tx) B2 and hydroxyeicosatetraenoic acids (HETEs) were present in both circulations of placentae from IDDM pregnancies. Levels of 6-keto prostaglandin F1a (6KPGF1a) were significantly reduced in both circulations in placentae from IDDM pregnancies. Thus, the ratio of TxA2 to PGI2 and the ratio of HETEs to PGI2 were both significantly increased in placentae from IDDM pregnancies. These results suggest an imbalance in eicosanoid production which may be relevant to abnormal placental structure and function in IDDM pregnancies.


Gonadotropin stimulation of K+ secretion and Na+ absorption by brook trout (Salvelinus fontinalis) sperm duct epithelium.
The sperm duct epithelium from mature spermiating brook trout (Salvelinus fontinalis) was mounted in vitro to examine control of Na+ absorptive and K+ secretory transport. Na+ absorption (measured as the short-circuit current) and K+ secretion (measured using 86Rb+ as tracer) were stimulated by 3-isobutyl-1-methylxanthine and cyclic AMP while unstimulated tissues had no net ion transport. Purified chum salmon (Oncorhynchus nerka) Con AII carbohydrate-rich gonadotropin produced a rapid, sustained rise in Rb+ secretion and Na+ uptake in a log linear dose-dependent manner. Addition of gonadotropin to either apical (mucosal) or basolateral (serosal) sides evoked the response, but addition to the apical side produced the more rapid effect, indicating that receptors for the hormone are present on both sides of the transporting cells and suggesting that subepithelial tissue may slow the response to serosally added hormone. This is the first indication that gonadotropin may directly regulate ion transport functions of the blood-testis barrier of vertebrates and in this way regulate seminal plasma ionic composition.


Biological clearance of HEMA in guinea pigs.
No toxicokinetic data are available about the dental composite component 2-hydroxyethylmethacrylate (HEMA) in vivo in the literature. Therefore, the excretion of HEMA in feces and urine in vivo and, using the pendular perfusion technique with segments of jejunum and colon, in the biliary and enteric excretion in situ were investigated in anesthetized guinea pigs. In the in situ experiments, guinea pigs (n = 4) received HEMA (0.02 mmol/kgbw labelled with a tracer dose 14C-HEMA 0.3 kBq/gbw) injected into the jugular vein. In the in vivo experiments, guinea pigs (n = 4) received HEMA (+ 14C-HEMA, same dose as above) via gastric tube. Urine and feces were collected for 24h. In the in situ experiments, organs from guinea pigs were removed 60 min after the beginning of the experiment, and then the 14C-radioactivity was measured. During the 60 min perfusion period the calculated amount of 14C-activity excreted into the total jejunum and colon was 6.0 +/- 1.0% and 2.7 +/- 0.7% of the dose administered, respectively (mean +/- sem). Of the 14C-HEMA dose, 5.3 +/- 0.3% was found in the bile. Significantly (p < 0.05) higher bile/blood concentration ratios were found at 10-40 min after the injection of HEMA, as compared to the ratio at 60 min. The total 14C-recovery in all organs tested was 20.0 +/- 2.6%. During 24h the amounts of 14C-activity excreted in the feces and urine were 1.1 +/- 0.1% or 17.1 +/- 1.50% of the dose administered, respectively (mean +/- sem). The total 14C-recovery in all organs tested was 11.6 +/- 0.6%. In a second series of in vivo experiments, exhaled air from the animals was captured during the 24h experimental period. 14C was exhaled to 63.6 +/- 2.11% of the administered 14C-HEMA dose (mean +/- sem; n = 4) as 14C-carbondioxide. The results indicate a rapid clearance of 14C-HEMA and/or 14C-HEMA metabolite(s) from the organism, exhalation being the major route of elimination.


Computer analysis of interacting dopaminergic and cholinergic control mechanisms in the extrapyramidal system.
The experimental results of many authors suggest that the output activity of the extrapyramidal motor control system depends on a balance between the levels present of the chemical transmitters dopamine and acetylcholine. In this paper it is proposed that these results are best explained by two feedback regulatory systems interconnected with positive interaction--in the sense of the relative gain array (Bristol, 1966). Using the computer-aided design procedure CAIAD, a simple two-input two-output model is simulated so as to give responses similar to those observed when dopaminergic or cholinergic drugs are applied. The effect of reducing the gain in one control loop corresponds to the effect of lesioning part of the extrapyramidal system in the brain. In addition, the effect of an anti-schizophrenic drug such as haloperidol is interpreted as a disturbance input on one of the interacting paths.


Efficient recovery of a functional extracellular domain of bovine IgG2 Fc receptor (boFcgamma2R) from inclusion bodies by a rapid dilution refolding system.
The extracellular domain of the boFcgamma2R gene was constructed and cloned into the Escherichia coli expression vector pET-28a. The recombinant protein was expressed at high level in E. coli BL21(DE3) and existed mainly as inclusion bodies. The inclusion bodies were solubilized in 6 M guanidine hydrochloride and refolded by rapid dilution. After renaturation, the purity of the recovered recombinant protein was up to 95%. ELISA assay showed that the renatured recombinant protein could inhibit bovine IgG2 binding to expressed boFcgamma2R on the COS-7 cell surface with an IC50 value of 0.68 microM. The overall yield of the active rsbo2R was up to 20 mg/l of culture. Crystals of the rsbo2R were grown at 293 K by the hanging-drop vapour diffusion method showed weak diffraction.


Mesh Type With Ventral Hernia Repair: A Systematic Review and Meta-analysis of Randomized Trials.
Synthetic mesh is widely utilized for clean ventral hernia repair; however, it is unclear if synthetic mesh provides the same benefits with high-risk patients or during contaminated cases. Many surgeons use biologic mesh in these settings, but there is little evidence to support this practice. Our objective was to compare the clinical outcomes of utilizing biologic mesh versus synthetic mesh during ventral hernia repair. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a review of the literature was conducted using Cochrane library, EMBASE, Clinicaltrials.gov, and PubMed for randomized controlled trials published that compared biologic versus synthetic mesh during ventral hernia repair. The primary outcome was major complications defined as deep or organ space surgical site infection, reoperations, and hernia recurrences. Of 1889 manuscripts screened, four publications were included. The four studies included a total of 758 patients, with 381 receiving biologic mesh and 377 receiving synthetic mesh. Compared to biologic mesh, synthetic mesh had lower rates of major complications (38.6% versus 23.4, risk ratio = 0.55, 95% confidence interval = 0.35 to 0.86, P = 0.009) and hernia recurrence (24.5 % versus 10.3%, risk ratio = 0.44, 95% confidence interval = 0.28 to 0.69, P = 0.004). In addition, there was a lower percentage of surgical site infection and reoperation in the synthetic mesh group. Contrary to current surgical teaching, placement of permanent synthetic mesh into a contaminated field yielded rates of complications that were comparable or reduced compared to biologic mesh.


Efficacy and Safety of Evening Administration of Controlled-Delivery Diltiazem Capsules in Chronic Stable Angina Patients.
The safety and efficacy of controlled-delivery (CD) once-a-day formulation of diltiazem administered in the evening, at a dose of 240 mg, was assessed in 37 patients with stable angina pectoris. A double-blind, placebo-controlled, randomized, crossover protocol was used. Following a 4-day washout period, patients entered a 5--7-day single-blind placebo run-in period during which qualification and reproducibility exercise treadmill tests (ETTs) were performed 24 h postdose. Eligible patients were randomized in a double-blind fashion, to either CD diltiazem or to placebo for a 7--10-day treatment period. They then entered a 5--7-day single-blind washout period, after which they received the alternate treatment for another 7 to 10 days. ETTs were performed at the end of each treatment period. Compared to placebo, evening administration of CD diltiazem produced a marked improvement of the time to ETT termination, time to onset of angina, and time to 1 mm ST depression. In addition, the number of angina attacks recorded in patient diaries was reduced compared to placebo. Incidence of adverse events was comparable with CD diltiazem and placebo. We conclude that evening administration of controlled-delivery diltiazem is highly effective and safe in the treatment of stable angina pectoris.


'I tell them that sex is sweet at the right time' - A qualitative review of 'pleasure gaps and opportunities' in sexuality education programmes in Ghana and Kenya.
Pleasure is a key motivator for sex globally, while unsafe sex is the largest risk factor for young women's mortality and the second for young men. However, framing of sex education and sexual health programmes continues to be around avoiding danger, death and disease, rather than striving for pleasurable, satisfying, and safe sexual experiences. Omission of pleasure and sex-positivity goes against growing evidence that shows that people with more positive views of sexuality are more likely to practice safer sex, use contraception consistently, have higher sexual self-esteem and be more assertive.The Pleasure Project and Rutgers, with GH SRHR Alliance (Ghana) and SRHR Alliance (Kenya), conducted a qualitative pilot study of sexuality education under the Get Up Speak Out programme, analysing the extent to which they included sex-positive content, with recommendations to enhance sex-positivity. Data were collected through interviews with facilitators, focus group discussions with learners, observation of sessions, and curricula content analysis. Findings reveal possibilities of sex-positivity in restrictive contexts, illustrating ways for sexuality education to become more sex-positive and pleasure inclusive. This study enables the development of a new tool for a 'pleasure audit', with markers of high-quality, sex-positive and pleasure-inclusive sexuality education or sexual health programmes.


Deficits in inhibition and flexibility are associated with the APOE-E4 allele in nondemented older adults.
This prospective study of nondemented older adults at genetic risk for AD and other types of dementia (i.e., APOE e4 allele) utilized a new Stroop test that includes a dual executive-function condition requiring both response inhibition and cognitive switching. Results indicated that, relative to non-e4 subjects, the e4 group committed more errors, but only on the new Inhibition/Switching condition. In addition, error-rate variance on this task was more heterogeneous for the e4 compared to the non-e4 group, and errors rates correlated significantly with global cognitive status (i.e., DRS scores) for the e4 group but not for the non-e4 group. These findings suggest that vulnerability to errors in response inhibition and cognitive flexibility is present in persons at risk for AD and may signal early emergence of executive dysfunction in preclinical AD. The association between these subtle executive-function deficits and the overall cognitive functioning of at-risk individuals provides further evidence of their utility as a possible preclinical marker of AD.


Optimization of Sample Preparation for the Identification and Quantification of Saxitoxin in Proficiency Test Mussel Sample using Liquid Chromatography-Tandem Mass Spectrometry.
Saxitoxin (STX) and some selected paralytic shellfish poisoning (PSP) analogues in mussel samples were identified and quantified with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sample extraction and purification methods of mussel sample were optimized for LC-MS/MS analysis. The developed method was applied to the analysis of the homogenized mussel samples in the proficiency test (PT) within the EQuATox project (Establishment of Quality Assurance for the Detection of Biological Toxins of Potential Bioterrorism Risk). Ten laboratories from eight countries participated in the STX PT. Identification of PSP toxins in naturally contaminated mussel samples was performed by comparison of product ion spectra and retention times with those of reference standards. The quantitative results were obtained with LC-MS/MS by spiking reference standards in toxic mussel extracts. The results were within the z-score of ±1 when compared to the results measured with the official AOAC (Association of Official Analytical Chemists) method 2005.06, pre-column oxidation high-performance liquid chromatography with fluorescence detection (HPLC-FLD).


Intron Retained, Transcript Detained: Intron Retention as a Hallmark of the Quiescent Satellite Cell State.
Molecular signatures defining quiescence in muscle satellite cells (mSCs) remain enigmatic. In this issue of Developmental Cell, Yue et al. adapted an in vivo fixation approach to isolate dormant mSCs from healthy muscle. Characterizing the transcriptome from these cells, they identified intron retention as a novel hallmark of mSC quiescence.


Ganglion cyst of Hoffa's fat pad of knee-a rare cause of knee pain and swelling-a case report and literature review.
Ganglion cysts around knee joint are uncommon and that from Hoffa's fat pad are even rarer. We present a case of 30 year old male patient with complaint of pain and swelling in left knee joint. Radiograph did not show any bony abnormality. MRI showed large tubulocystic lesion within Hoffa's fat pad which showed low signal intensity on T1-weighted images and high signal intensity on T2-STIR images. Open excision of the lesion was done. Histopathology of the specimen confirmed the diagnosis of the ganglion cyst. In follow-up, patient had asymptomatic left knee with full range of motion and did not show any sign of recurrence. Ganglion cysts from fat pad though very rare but should be considered in differential diagnosis to have an early diagnosis and management. Symptomatic ganglion cyst should be excised by open procedure or arthroscopically depending upon the size and extent of the lesion.


Prevalence of pharyngeal and laryngeal abnormalities in Thoroughbreds racing in Australia, and their association with performance.
Little information is available regarding the prevalence of abnormalities of the upper airway and their association with performance in the general population of Thoroughbred racehorses. To describe the prevalence of selected abnormalities of the upper airway and their association with performance in Thoroughbred racehorses in Australia. That abnormalities of the upper airway of Thoroughbred racehorses are associated with poor race performance. Rhinolaryngoscopy was performed after racing and presence and characteristics of abnormalities of the larynx and pharynx were recorded in a prospective cross-sectional study of Thoroughbred horses racing in Victoria, Australia. Rhinolaryngoscopy was performed once on each of 744 horses over 35 months. Fifty abnormalities of the upper airway were detected in 47 horses (6.3%, 95% confidence interval [CI] 4.7-83%). Epiglottic entrapment was detected in 7 horses (0.9%, 95% CI 0.4-1.9%) and was significantly (P = 0.015) associated with superior performance. Grade 2 asymmetry (4 grade scale) of the left arytenoid cartilage was detected in 9 horses (1.2%, 95% CI 0.5-2.4%) and was also associated with superior performance (P<0.001). Ulceration or erosion of the mucosa of the axial surface of one or both arytenoids was detected in 18 horses (2.4%, 95% CI 13-3.8%) and was not associated with alterations in exercise performance (P = 0.31). Epiglottic entrapment, Grade 2 laryngeal asymmetry and mucosal erosions detected in Thoroughbred racehorses were not associated with impaired performance; therefore, surgical correction and concern over laryngeal function in horses with Grade 2 asymmetry may not be necessary in individuals performing to expectation.


Plasmids of Selenomonas ruminantium and development of host-vector system.
A high frequency of plasmids was detected in the rumen bacterium Selenomonas ruminantium. Plasmids 0.9-20 kb in size were detected in more than 50% tested strains. Densitometric analysis indicated that plasmid DNA could represents more than 25% of total cellular DNA. Up to six plasmids were detected in strain S. ruminantium 18. Two smallest cryptic plasmids pSRD181 and pSRD182 from this strain were cloned into Escherichia coli vector pBluescriptSK+ and partially characterized. The plasmid pSRD181 is 1.4 kb and pSRD182 is 2.0 kb. While computer analysis of pSRD181 sequence data showed high homology with replication protein of Staphylococcus aureus plasmids, the pSRD182 sequence showed no significant homology in GenBank data. Strain S. ruminantium 28 was successfully transformed with pJW1 derived plasmid pJ1B1 using ampicillin resistance gene as marker. This is the first report on transformation of selenomonads with foreign DNA.


Rapid non-genomic effects of glucocorticoids on oxidative stress in a guinea pig model of asthma.
Glucocorticoids (GC) may exert therapeutic effects in asthma by a rapid non-genomic mechanism. The lungs of asthmatic patients are exposed to oxidative stress, which is believed to be critical in the pathogenesis of asthma. The aim of this study was to investigate whether GC exert a rapid non-genomic effect on oxidative stress in asthmatic guinea pigs. The guinea pig asthma model was used to assess inhibitory effects of budesonide (BUD) on oxidative stress. BAL fluid (BALF), trolox equivalent antioxidant capacity and lung manganese superoxide dismutase (MnSOD) activity were measured by spectrophotometry. Superoxide anion production was measured by cytochrome c reduction assay. Oxidative stress occurred within minutes following antigen challenge and BUD reduced the severity of oxidative stress in asthmatic guinea pigs within 15 min. BUD significantly decreased BALF trolox equivalent antioxidant capacity and lung MnSOD activity, as compared with those of vehicle-treated asthmatic guinea pigs (P < 0.05). Additionally, BUD rapidly inhibited in vitro superoxide anion production by BALF cells and bronchi harvested from sensitized animals. These rapid effects were not blocked by the GC receptor antagonist RU486 and/or the protein synthesis inhibitor cycloheximide. BUD reduced oxidative stress in a guinea pig model of asthma by a rapid non-genomic mechanism. These data suggest new mechanisms whereby GC treatments may benefit asthma.


Rod influence on hue-scaling functions.
Rod influence on hue appearance of spectral lights was characterized by comparing the scaling of red, green, yellow, and blue hue sensations for an 8 degrees-diameter, 7 degrees-eccentric test spot under conditions that minimized (cone plateau) and maximized (dark adapted) rod influence at two mesopic light levels (1.5 and 3.0 log scoptic trolands). At the lower light level, the hue-scaling functions showed that rod signals influenced the spectral range and magnitude of all four primary hues. The rod influence could not be characterized as a ubiquitous augmentation or diminution of any hue over the entire spectrum. This constrains models of rod influence on color vision.


[A case of choroidovitreal neovascularization after unsuccessful laser chorioretinal venous anastomosis for central retinal vein occlusion].
A case of nonischemic central retinal vein occlusion, which developed severe neovascular complication after unsuccessful laser chorioretinal venous anastomosis is reported. The patient was a 50-year-old man with nonischemic central retinal vein occlusion of the right eye. Two weeks after laser chorioretinal venous anastomosis attempt, closure of the venous segment distal to the anastomotic sites occurred and a choroidovitreal neovascularization developed, so that vitreous surgery was needed 2 months after the laser attempt. Laser chorioretinal venous anastomosis should be used only on carefully selected patients, and close follow-up is needed after this treatment.


A functional SNP in miR-146a and genetic susceptibility to drug-resistant epilepsy.
The study aimed to assess the relationship between the functional single nucleotide polymorphism (SNP) (rs57095329) of miR-146a, the progression of drug-resistant epilepsy (DRE), and the severity of the disease (seizure frequency) in a group of Egyptian children epilepsy patients. 110 Egyptian children were recruited and divided into two groups, the epilepsy patients (n = 60) and the healthy control children (n = 50). The patient's group was equally subdivided into two subgroups: drug-resistant and drug-responsive epilepsy patients. Genomic DNA samples from all participants were screened for the incidence of the rs57095329 SNP of the miR-146a gene by the Real-Time PCR. There was no statistical significance between epilepsy patients compared to controls regarding the rs57095329 SNP genotypes and alleles. Contrarily, there was significant difference between the drug-resistant epilepsy and the drug-responsive cases (P < 0.05). The genotypes AG (P < 0.007, OR: 0.118, 95% CI (0.022-0.636)) and GG (P = 0.016, OR: 0.123, 95% CI (0.023-0.769)) were higher among the drug-resistant, while AA was higher among the drug-responsive patients. The alleles A and G were higher among all cases, with a statistically significant difference (P = 0.028, OR: 0.441, 95% CI (0.211-0.919)). A significant difference was reported in the dominant model (AA versus AG+GG) (P = 0.005, OR: 0.12395% CI (0.025-0.621)). Therefore, miR-146a might be a potential therapeutic target for epilepsy treatment. The study was limited by the low number of young epileptic patients, the refusal of some parents to participate, and the incomplete medical history of some cases in the study, which forced their exclusion. More studies might be necessary to investigate other effective drugs to overcome the resistance issues induced by miR-146a rs57095329 polymorphisms.


Use-effectiveness of the female versus male condom in preventing sexually transmitted disease in women.
Data are limited on the female condom's effectiveness against STDs. The goal was to compare STD rates between women given small-group education on, and free supplies of, either female or male condoms. Female patients at an STD clinic (n = 1442) were randomly assigned to condom type and followed via medical records for STDs (gonorrhea, chlamydia, early syphilis, or trichomoniasis). In an intention-to-treat analysis, the odds ratio for a comparison of STD occurrence between the female and male condom groups was 0.75 (95% confidence interval [CI], 0.56-1.01), and it did not change with adjustment. In a second analysis among women returning for subsequent screening, incidence rates for the first new postintervention STD per 100 woman-months of observation were 6.8 in the female condom group and 8.5 in the male condom group (rate ratio = 0.79 [CI, 0.59-1.06]). Compared with those provided with male condoms alone, women counseled on, and provided with, female condoms fared no worse and experienced a nonsignificant reduction in STDs.


How are cytokines activated in heart failure?
In the dilated and failing heart, elevated LV end-diastolic wall stress causes myocardial expression of cytokines, which directly or indirectly influence LV contractile performance and remodeling [22]. Due to poor diffusion of cytokines into the coronary effluent, the contribution of this myocardial production to the raised plasma levels is probably limited. Raised plasma levels of cytokines in heart failure are therefore more likely the result of extramyocardial production because of altered tissue perfusion and tissue hypoxia possibly modulated by bacterial endotoxin release from the gut.


Distribution, biosynthesis and catabolism of methylxanthines in plants.
Methylxanthines and methyluric acids are purine alkaloids that are synthesized in quantity in a limited number of plant species, including tea, coffee and cacao. This review summarizes the pathways, enzymes and related genes of caffeine biosynthesis. The main biosynthetic pathway is a sequence consisting of xanthosine → 7-methylxanthosine → 7-methylxanthine → theobromine → caffeine. Catabolism of caffeine starts with its conversion to theophylline. Typically, this reaction is very slow in caffeine-accumulating plants. Finally, the ecological roles of caffeine and the production of decaffeinated coffee plants are discussed.


Pilot testing a tool to determine the costs and time associated with community pharmacy-based administration of injectable naltrexone.
Medications for opioid use disorder (MOUD), including injectable naltrexone (IN), are part of evidence-based OUD treatments. MOUD access often is limited, especially in rural communities. When authorized to administer non-vaccination injections, pharmacists can increase IN accessibility. However, inadequate reimbursement for pharmacist-administered IN can hinder widespread adoption. To pilot test a process to obtain a preliminary estimate of the total costs and time associated with community-pharmacist administered IN. A purposively-selected sample of key informants at community pharmacies administering IN were surveyed about time and cost for best practice IN activities. Respondents estimated the time to perform activities and average pharmacist/pharmacy technician hourly salary, which were used to calculate administration costs. The approach to estimate time and costs was feasible. Administrative costs (mean = $93, range: $48-$164) and time (mean = 123 min., range: 63-220 min.) to administer IN varied widely. Pharmacists'/pharmacy technicians' roles varied by pharmacy. Pharmacists allocate significant time and resources to administer IN. Insufficient reimbursement may disincentivize pharmacy-involved OUD treatment and ultimately slow needed expansion of MOUD services. Increasing IN services requires engaging pharmacies to expand their practice through educational campaigns, along with a commitment to reimburse the cost of medications and related administration activities.


Iron metabolism and lipid peroxidation products in infants with hypoxic ischemic encephalopathy.
Iron delocalization or misregulation of iron metabolism may play a critical role in the pathology of hypoxic ischemic encephalopathy (HIE). To study iron metabolism and lipid peroxidation in newborn infants and to correlate non-protein-bound iron (NPBI) concentration with the severity of the post-asphyxial injury and subsequent short-term outcomes. Concentrations of NPBI and malondialdehyde (MDA) in the serum and in the cerebrospinal fluid (CSF) were measured in eight healthy newborn infants and nine newborn infants suffering from moderately severe HIE. Short-term outcomes (death, survival with or without neurological abnormality) were noted at hospital discharge. Serum and CSF concentrations of both NPBI and MDA were significantly increased in HIE infants when compared to controls. Serum iron was significantly increased and total iron binding capacity was significantly decreased in HIE infants compared to controls. Out of the nine HIE infants, four infants died and two infants survived with abnormal neurological findings at hospital discharge. These six infants with clinical sequels had significantly increased concentrations of NPBI in the serum and in the CSF; and increased concentrations of MDA in the CSF when compared to the other three who survived without short-term abnormalities. We conclude that hypoxia ischemia alters iron metabolism and lipid peroxidation in newborn infants; and that NPBI and MDA in the CSF are increased in infants with HIE. This study supports a role for iron in oxidative injury to the central nervous system after hypoxic ischemic insults.


Effect of iodinated contrast media on thyroid function in adults.
Excess free iodide in the blood (ingested or injected) may cause thyrotoxicosis in patients at risk. Iodinated contrast medium solutions contain small amounts of free iodide and may be of significance for patients at risk. The free iodide may also interfere with nuclear medicine diagnostic studies and treatment. Therefore the Contrast Media Safety Committee of the European Society of Urogenital Radiology reviewed the literature on this subject in order to prepare guidelines. A report and guidelines were prepared based on an extensive Medline search. The report was discussed with the participants attending the Tenth European Symposium on Urogenital Radiology, Uppsala, Sweden, September 2003. Contrast medium induced thyrotoxicosis is rare. Contrast medium injection does not affect thyroid function tests (e.g., T3, T4, TSH) in patients with a normal thyroid. Routine monitoring of thyroid function tests before contrast medium injection in patients with a normal thyroid is not indicated even in areas where there is dietary iodine deficiency. Patients at risk of developing thyrotoxicosis after contrast medium injection are patients with Graves' disease and patients with multinodular goiter with thyroid autonomy, especially elderly patients and patients living in areas of iodine deficiency. Patients at high-risk should be carefully monitored by endocrinologists after contrast medium examinations. Prophylaxis in these groups is not generally recommended, although it may offer some protection in selected high-risk individuals. The free iodide load of contrast media injections interferes with iodide uptake in the thyroid and therefore compromises diagnostic thyroid scintigraphy and radio-iodine treatment of thyroid malignancies for 2 months after administration of contrast media. Simple guidelines on the subject are proposed.


Measuring cardiomyocyte cellular characteristics in cardiac hypertrophy using diffusion-weighted MRI.
This paper presents a hierarchical modeling approach for estimating cardiomyocyte major and minor diameters and intracellular volume fraction (ICV) using diffusion-weighted MRI (DWI) data in ex vivo mouse hearts. DWI data were acquired on two healthy controls and two hearts 3 weeks post transverse aortic constriction (TAC) using a bespoke diffusion scheme with multiple diffusion times ( Δ $$ \Delta $$ ), q-shells and diffusion encoding directions. Firstly, a bi-exponential tensor model was fitted separately at each diffusion time to disentangle the dependence on diffusion times from diffusion weightings, that is, b-values. The slow-diffusing component was attributed to the restricted diffusion inside cardiomyocytes. ICV was then extrapolated at Δ = 0 $$ \Delta =0 $$ using linear regression. Secondly, given the secondary and the tertiary diffusion eigenvalue measurements for the slow-diffusing component obtained at different diffusion times, major and minor diameters were estimated assuming a cylinder model with an elliptical cross-section (ECS). High-resolution three-dimensional synchrotron X-ray imaging (SRI) data from the same specimen was utilized to evaluate the biophysical parameters. Estimated parameters using DWI data were (control 1/control 2 vs. TAC 1/TAC 2): major diameter-17.4 μ $$ \mu $$ m/18.0 μ $$ \mu $$ m versus 19.2 μ $$ \mu $$ m/19.0 μ $$ \mu $$ m; minor diameter-10.2 μ $$ \mu $$ m/9.4 μ $$ \mu $$ m versus 12.8 μ $$ \mu $$ m/13.4 μ $$ \mu $$ m; and ICV-62%/62% versus 68%/47%. These findings were consistent with SRI measurements. The proposed method allowed for accurate estimation of biophysical parameters suggesting cardiomyocyte diameters as sensitive biomarkers of hypertrophy in the heart.


Over-expression of programmed death-ligand 1 and programmed death-1 on antigen-presenting cells as a predictor of organ dysfunction and mortality during early sepsis: a prospective cohort study.
This study aimed to explore the changes of programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) expression on antigen-presenting cells (APCs) and evaluate their association with organ failure and mortality during early sepsis. In total, 40 healthy controls and 198 patients with sepsis were included in this study. Peripheral blood was collected within the first 24 h after the diagnosis of sepsis. The expression of PD-L1 and PD-1 was determined on APCs, such as B cells, monocytes, and dendritic cells (DCs), by flow cytometry. Cytokines in plasma, such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, IL-10, and IL-17A were determined by Luminex assay. PD-1 expression decreased significantly on B cells, monocytes, myeloid DCs (mDCs), and plasmacytoid DCs (pDCs) as the severity of sepsis increased. PD-1 expression was also markedly decreased in non-survivors compared with survivors. In contrast, PD-L1 expression was markedly higher on mDCs, pDCs, and monocytes in patients with sepsis than in healthy controls and in non-survivors than in survivors. The PD-L1 expression on APCs (monocytes and DCs) was weakly related to organ dysfunction and inflammation. The area under the receiver operating characteristic curve (AUC) of the PD-1 percentage of monocytes (monocyte PD-1%)+APACHE II model (0.823) and monocyte PD-1%+SOFA model (0.816) had higher prognostic value than other parameters alone. Monocyte PD-1% was an independent risk factor for 28-day mortality. The severity of sepsis was correlated with PD-L1 or PD-1 over-expression on APCs. PD-L1 in monocytes and DCs was weakly correlated with inflammation and organ dysfunction during early sepsis. The combination of SOFA or APACHE II scores with monocyte PD-1% could improve the prediction ability for mortality.


Reduction of catechin astringency by the complexation of gallate-type catechins with pectin.
The reductive effect of pectin on tea catechin astringency was investigated by using a taste sensor system and (1)H-NMR spectroscopy. The sensor analysis revealed that the astringency of gallate-type catechins (EGCg and ECg) was reduced by the addition of pectin, whereas that of non-gallate-type catechins (EGC and EC) hardly changed. Changes in the (1)H-NMR chemical shifts of the catechins and pectin in mixed solutions showed that the gallate-type catechins formed complexes with pectin more closely than the non-gallate-type catechins. These results demonstrate that complexation between the gallate-type catechins and pectin is a factor for reducing catechin astringency.


The structure and organization of an eelgrass fish fauna.
Ten species of fish made up more than 95 percent of the standing crop of the total fish assemblage of a shallow-water eelgrass meadow in southeastern Australia. The relative abundance of each species remained fairly constant from year to year during a four and a half year period. Four species were permanent residents, three moved over the meadow at high tide, and the juveniles of three species changed residence status as they grew. Most species exhibited distinct diel patterns of activity, four species were diurnal and five were nocturnal. Species foraged in different microhabitats and dietary overlap was very low amongst all but two species which had overlapping habitat, prey and prey size preferences, but had different diel activity periods. Data on production by prey and consumption of prey by these two fish species indicated that competition for food was probably responsible for the temporal separation of feeding niches. Predation by birds and fish appeared to be the major influence on the diel activity period of one fish species. The maintenance of the patterns of resource allocation among the remaining species is discussed and the organization of different seagrass fish faunas is compared.


N,N-Dimethyl Formamide Regulating Fluorescence of MXene Quantum Dots for the Sensitive Determination of Fe3.
Due to the wide use of iron in all kinds of areas, the design and construction of direct, fast, and highly sensitive sensor for Fe3+ are highly desirable and important. In the present work, a kind of fluorescent MXene quantum dots (MQDs) was synthesized via an intermittent ultrasound process using N,N-dimethyl formamide as solvent. The prepared MQDs were characterized via a combination of UV-Vis absorption, fluorescence spectra, X-ray photoelectron energy spectra, and Fourier-transform infrared spectroscopy. Based on the electrostatic-induced aggregation quenching mechanism, the fluorescent MQDs probes exhibited excellent sensing performance for the detection of Fe3+, with a sensitivity of 0.6377 mM-1 and the detection limit of 1.4 μM, superior to those reported in studies. The present MQDs-based probes demonstrate the potential promising applications as the sensing device of Fe3+.


The genetic architecture of prolificacy in maize revealed by association mapping and bulk segregant analysis.
Here, we revealed maize prolificacy highly correlated with domestication and identified a causal gene ZmEN1 located in one novel QTL qGEN261 that regulating maize prolificacy by using multiple-mapping methods. The development of maize prolificacy (EN) is crucial for enhancing yield and breeding specialty varieties. To achieve this goal, we employed a genome-wide association study (GWAS) to analyze the genetic architecture of EN in maize. Using 492 inbred lines with a wide range of EN variability, our results demonstrated significant differences in genetic, environmental, and interaction effects. The broad-sense heritability (H2) of EN was 0.60. Through GWAS, we identified 527 significant single nucleotide polymorphisms (SNPs), involved 290 quantitative trait loci (QTL) and 806 genes. Of these SNPs, 18 and 509 were classified as major effect loci and minor loci, respectively. In addition, we performed a bulk segregant analysis (BSA) in an F2 population constructed by a few-ears line Zheng58 and a multi-ears line 647. Our BSA results identified one significant QTL, qBEN1. Importantly, combining the GWAS and BSA, four co-located QTL, involving six genes, were identified. Three of them were expressed in vegetative meristem, shoot tip, internode and tip of ear primordium, with ZmEN1, encodes an unknown auxin-like protein, having the highest expression level in these tissues. It suggested that ZmEN1 plays a crucial role in promoting axillary bud and tillering to encourage the formation of prolificacy. Haplotype analysis of ZmEN1 revealed significant differences between different haplotypes, with inbred lines carrying hap6 having more EN. Overall, this is the first report about using GWAS and BSA to dissect the genetic architecture of EN in maize, which can be valuable for breeding specialty maize varieties and improving maize yield.


[Influenza incidence estimated with a rapid diagnostic test in critically ill patients with acute respiratory failure during the 2005 and 2006 winter flu epidemics].
To estimate the incidence of influenza infection with a rapid diagnostic test in patients hospitalized in an intensive care unit (ICU) during the epidemic periods of two consecutive winters (2005-2006). This study tested nasal aspirate of all patients admitted to the ICU for acute respiratory failure during the influenza epidemic period with the QuickVue influenza rapid diagnostic test. The study included 39 patients: 22 men and 17 women. Their mean age was 69.7+/-13 years, their mean SAPS II score 54+/-21, their mean length of stay 14.7+/-20 days, and 43.5% had been vaccinated against influenza. The mortality rate was 33.3% (n=13). Four patients (10.2%) had a positive QuickVue test and were considered to have influenza associated with their primary diagnosis: pneumococcal pneumonia, haemophilus pneumonia, acute bronchitis, and acute bronchitis with acute cardiogenic edema. These patients were older than those with a negative test (80+/-7 versus 68+/-13 years, p=0.02). Their SAPS II, length of stay and mortality rate did not differ statistically from those with negative results. Chronic heart failure (but not COPD or non-vaccination) was more frequent in these patients (p=0.01). Several published studies report a satisfactory specificity and sensitivity for QuickVue. With this test, we estimated the incidence of influenza in patients hospitalized in our ICU for acute respiratory failure during flu epidemics at around 10%, close to that reported in previous studies.


A prospective, randomized, single-blinded trial for improving health outcomes in rhinology by the use of personalized video recordings.
Clear patient-physician communication is critical in improving patient compliance, outcomes, and satisfaction. However, constraints of shortened clinic visits, patient anxiety, and poor recall can cause significant barriers to effective communication. We hypothesized that the ability to view patient-physician counseling videos at home would improve health outcomes. Patients in a tertiary rhinology clinic were enrolled into a single-blinded prospective study after obtaining institutional review board (IRB) approval and informed consent. All enrollees had a short summary of their clinical encounter video-recorded with a tablet using Medical Memory, a Health Insurance Portability and Accountability Act (HIPAA)-compliant software system. Patients were randomized to receive access to their videos by our research coordinator, and outcomes included questionnaires at the first postoperative visit to assess patient recall and satisfaction. A total of 101 patients were enrolled. Half of those with video access watched the video at least once, on average 3.44 times. Of those without access, 90% would have liked the option. Those with video access had a higher percentage of correct answers to questions regarding surgical risk and extent of surgery; however, there was no significant difference between the 2 groups. Our results show that patients in both groups were enthusiastic about this technology and often shared their videos with family and friends. Video-recordings of physician-patient encounters may be a possible solution to improve physician-patient communication.