The relationship between reported domestic canine parvovirus cases and wild canid distribution.
Canine parvovirus (CPV) is an important and often fatal pathogen of domestic dogs. It is resistant in the environment and cross-species transmission has been indicated in some canid populations, but never in Australia. The aim of this study was to determine if an association exists between 1. reported CPV cases in domestic dogs, and 2. the wild canid distribution in New South Wales (NSW), Australia. Reported CPV cases, and reports of the presence of wild dogs and the red fox (Vulpes vulpes), were extracted from a voluntary surveillance database and a voluntary pest reporting system, respectively. A total of 1,984 CPV cases in domestic dogs, and 3,593 fox and 3,075 wild dog sightings were reported between 2011 and 2016. Postcodes in which CPV cases were reported were significantly (P = 0.0002) more likely to report wild dogs (odds ratio 2.07, 95% CI 1.41-3.03). Overall, CPV cases were significantly (P < 0.05) correlated with both fox reports (rSP 0.225) and wild dog reports (rSP 0.247). The strength of association varied by geographical region and year; the strongest correlations were found in the mid-North Coast region (rSP 0.607 for wild dogs) and in 2016 (rSP 0.481 for foxes). Further serological and virological testing is required to confirm the apparent and plausible association between domestic CPV cases and wild canid distribution found in this study.


Ecological risk assessment and corrective actions for dioxin-polluted sediment in a chemical plant's brine water storage pond.
Despite the known high toxicity of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs, or dioxins), there are few case studies of PCDD/Fs contamination in sediment and there remains much to learn regarding their ecological impact. In this study, we performed an environmental risk assessment of a brine water storage pond near a chemical plant with high PCDD/Fs pollution potential before and after corrective actions. We found PCDD/F accumulation in the pond's fish and crab from the brine water storage pond, and the PCDD/Fs concentrations in biota higher than Taiwan's food safety standard (3.5 pg-TEQ/g). Furthermore, we found a high degree of pollution using different indices, including contamination factor (CF), modified degree of contamination (mCd), and pollution index (PI), in the pond's sediment. Before corrective actions, we also found high risk in the PCDD/F contamination in the sediment using various biological risk indices, including potential ecological risk index (RI) and risk quotient (RQ). After the corrective actions, including institutional/engineering control and remediation, the CF, mCd, and PI had decreased by 20-41 % and RI and RQ by 41-56 %. In addition, despite the slight reduction of pollution and risk index values in the whole pond, significant reduction was observed in the sediment of highly polluted area A owing to the lower disturbing suction dredging. In conclusion, the corrective actions used in this study helped decrease the pollution and ecological risk associated with this site's PCDD/Fs polluted sediment to some extent, suggesting that contamination and risk could be reduced to acceptable levels if these corrective actions are continued.


Thermal perturbation studies of membrane-bound acetylcholine receptor from Torpedo: effects of cholinergic ligands and membrane perturbants.
Thermal perturbation techniques have been used to probe structural features of the nicotinic acetylcholine receptor (AcChR). The information obtained from differential scanning calorimetry (DSC) of AcChR membranes (M.C. Farach and M. Martinez-Carrion (1983) J. Biol. Chem. 258, 4176) in the absence and in the presence of cholinergic ligands and local anesthetics, is comparable to that obtained from a simpler technique of heat inactivation of the alpha-bungarotoxin (alpha-Bgt) binding sites on the AcChR protein in similar samples. When AcChR membranes are heated at approximately 1 degree C/min, heat inactivation of toxin binding sites has a characteristic T50 value (temperature at which 50% of the initial capacity to bind alpha-Bgt remains) of approximately 60 degrees C. When heated at a constant temperature during increasing periods of time, the rate at which heat inactivation occurs is also characteristic of the temperature chosen for the experiment. The above thermal parameters are also sensitive to perturbation of the AcChR membrane matrix by the presence of subsolubilizing concentrations of detergents. Moreover, elimination of detergents by dialysis allows us to evaluate the reversibility or irreversibility of AcChR thermal destabilization induced by detergents or other membrane perturbants. Under the experimental conditions used, structural destabilization induced by octylglucoside or cholate can be fully reversed by detergent dialysis, while that exerted by deoxycholate cannot. "Thermal gel" analysis of the aggregation of AcChR subunits induced by heat (G. Soler, J. R. Mattingly, and M. Martinez-Carrion (1984) Biochemistry 23, 4630) has also been used to assess the effects of detergent presence on the AcChR protein. When deoxycholate is used as the perturbing agent, there is a particularly effective sulfhydryl-mediated aggregation of the gamma-delta subunit group, which appears to correlate with the irreversible destabilization of alpha-Bgt binding sites induced by that detergent.


Fecal microbiota transplantation for recurrent Clostridium difficile infection: The patient experience.
Although effectiveness of fecal microbiota transplantation (FMT) has been adequately documented, the patient experience of undergoing FMT has not. We carried out a qualitative interview study using semistructured questions relating to aspects of health pre-FMT, during FMT, and post-FMT periods with 17 participants. Inductive coding was used to identify core themes during the periods. Pre-FMT themes included physical (continuous diarrhea and weight loss), mental (depression, wanting to die, and fear), quality of life (unable to perform normal activities), social support, and financial (medication costs) factors. Provider resistance/limited awareness were barriers to FMT. Participants reached a tipping point, experiencing feelings of hopelessness, which led them to pursue FMT. During FMT, participants commented on lack of a so-called ick factor. During the posttreatment period, participants experienced symptom relief, but had residual fears. Patient activation was present during all phases, including information seeking and empowerment. During the pre-FMT period, participants experienced extreme discomfort and encountered FMT barriers. Undergoing FMT was reported as easy but residual fear remained. There were displays of patient activation at all FMT time periods, including the seeking of FMT. Participants could have benefited from having undergone FMT sooner, demonstrating a need for improvement in provider education and health system barriers regarding FMT.


Chinese parents' support of preschoolers' mathematical development.
Research has documented the critical role played by the early home environment in children's mathematical development in Western contexts. Yet little is known about how Chinese parents support their preschoolers' development of math skills. The Chinese context is of particular interest because Chinese children outperform their Western counterparts in math, even early in development. The current study sought to fill this gap by examining a sample of 90 families of 4- and 5-year-olds from mainland China. Parental support-as measured by the frequency of parent-child engagement in home activities as well as parent number talk-and parents' role in children's numeracy skills were investigated. Results indicate wide variation among parents in both types of support. Frequency of engagement in formal numeracy activities, including counting objects and reading number story books, was related to children's knowledge of cardinality. A principal components analysis did not identify informal numeracy activities as a distinct home activity component, likely due to the infrequent occurrences of game-like numeracy activities among the Chinese families. Instead, a structured activity component emerged (e.g., playing musical instruments) and was positively related to children's arithmetic skills. Diversity, but not quantity, of parent number talk was related to children's symbolic magnitude understanding. The distinctive relationships between specific parental measures and child outcomes speak to the need for nuanced identification of home environment factors that are beneficial to particular math competencies. The findings also suggest cultural variations in the mechanisms that support children's mathematical development, highlighting the merits of investigating this topic in non-Western contexts.


High gene flow levels lead to gamete wastage in a desert spider system.
Field censuses, breeding experiments, and a quantitative model are used to obtain insight into the extent and consequences of genetic mixing between locally adapted populations of a desert spider. Typically, 9% of the matings of desert riparian spiders (non-aggressive phenotype) in native habitat involve an arid-land partner (aggressive phenotype). Mating was found to be random with respect to behavioral phenotype, but linearly related to both the rate of immigration and survival of immigrants from surrounding arid habitats in the riparian area. Genetic mixing between riparian and arid-land spiders produces offspring that exhibit lower rates of survival in riparian habitat. Two extreme behavioral phenotypes were also observed in the field studies: approximately 5% of the female spiders attacked all males they encountered while another 22% ran from all potential mates. Punnett square analyses of the potential genotypes produced by introgression between arid- and riparian-adapted spiders indicate that these extreme phenotypes appear in F2 generation hybrids and backcrosses. Because there is a costly wastage of gametes in the case of mixed phenotype mating, model results indicate that within three generations of the cessation of gene flow, the riparian population would be free of mixed genotypes and moving towards genetic differentiation.


Evaluation of data-driven network analysis approaches for functional connectivity MRI.
Correlated low frequency fluctuations in the blood oxygenation level dependent signal have been widely observed in highly connected brain regions and are considered to be indicative of coordinated activity within those regions. A typical functional connectivity MRI study consists of hundreds of time points acquired from thousands of image voxels, and thus exploratory data analysis is a significant challenge. This paper investigates the utilization of analytical methods based upon graph theory that can potentially provide a data-driven approach to examining the relationships between and within groups of voxels. Three algorithms, based on reachable groups, path-length analysis, and hierarchical clustering, are described and evaluated in the relatively simple context of the rodent brain. Analysis indicates that (based on the cross-correlation coefficient) cortical voxels are the most strongly connected network nodes. These voxels exhibit stronger clustering than would be expected in a randomly connected graph, and the amount of clustering is dependent on the cross-correlation threshold chosen. The analysis algorithms identify core groups in somatosensory areas and indicate that left and right somatosensory regions are more strongly connected to each other than to midline cortical areas. The results show that algorithms based on graph theory are well-suited for the data-driven analysis of functional connectivity studies.


[Influence of atmospheric pressure and its variations on premature rupture of membranes].
In popular belief, a higher rate of premature rupture of membranes (PROM) might be associated with atmospheric pressure (AP) variations. Results of past studies are contradictory. We aimed to assess whether or not AP values influence the rate of PROM. We performed a retrospective longitudinal study of women admitted for PROM from January 1st, 2009 to December 3rd, 2009. AP values for 2009 were obtained at the local meteorological station. AP values (average, minimum and maximum) and its variations did not influence the rate of PROM for 341 patients included in the study, as well as in the group of 187 patients with a negative result of vaginal swab or amniotic fluid sample. After exclusion of premature PROM, mean AP variation the days before PROM was higher than AP variations of the days without PROM (6.3hPa IC95% [5.65-7.00] vs. 5.2 IC95% [4.70-5.79], P=0.029). No higher rate of occurrence of PROM was noticed during the days with low AP (AP less than average AP of the year equal to 1009hPa or AP less than normal AP equal to 1013.2hPa) or during the days with a high variability (maximal AP-minimal AP greater than 5hPa). Our data did not support the hypothesis that AP influence the rate PROM.


[Effect of xuefuzhuyu pill on patients with carotid atherosclerosis by colour Doppler ultrasonography].
To observe the effect of Xuefuzhuyu Pill (XFZYP) on carotid atherosclerosis. The patients were randomly divided into XFZYP group and aspirin control group. The status of the carotid plaque vessel wall and blood flow were observed by colored Doppler ultrasonography. (1) Plaque of 6 cases regressed, of 6 cases unchanged, of 1 case progressed after treatment of XFZYP. The area of plaques between baseline and after treatment decreased 0.11 +/- 0.05 cm and that of thickness reduced for 0.09 +/- 0.04 cm2 (P < 0.05) in XFZYP group. While plaque of 3 cases regressed, of 6 unchanged, of 2 cases progressed after treatment of aspirin. The area and thickness of plaque were reduced to 0.05 +/- 0.04 cm and 0.04 +/- 0.03 cm respectively. There were no statistic difference in aspirin group. (2) The intima-media thickness of common carotid artery decreased 0.13 +/- 0.03 mm in XFZYP group (P < 0.001 versus baseline), but there were no significant change after treatment of aspirin (P > 0.05). (3) There were no distinct change about peak systole, minimal diastole time average peak, pulsative index, resistive index in common carotid artery and internal carotid artery after treatment of XFZYP and aspirin. Colour Doppler ultrasonography of carotid artery provide a noninvasive, safe and valid opportunities for clinical trail. XFZYP can be useful for the treatment of carotid atherosclerosis.


Multifunctional carbon nanotubes for direct electrochemistry of glucose oxidase and glucose bioassay.
Polydopamine (Pdop) has recently been shown to adsorb to a wide variety of surfaces and serves as an adhesion layer to immobilize biological molecules. In this work, the multifunctional carbon nanotube (CNT) composites were prepared though the oxidation of dopamine at room temperature and subsequent electroless silver deposition by mildly stirring. The stable immobilization and direct electron transfer of glucose oxidase were achieved on the composite film modified glassy carbon electrode. The resulting electrode gave a well-defined redox peaks with a formal potential of about -482 mV (vs. SCE) in pH 7.0 buffer. The electron transfer rate constant was estimated to be 3.6 s(-1), due to the combined contribution of Pdop, CNTs and Ag nanoparticles with the help of Nafion. Furthermore, the method for detecting of glucose was proposed based on the decrease of oxygen caused by the enzyme-catalyzed reaction between glucose oxidase (GOD) and glucose. The linear response to glucose ranging from 50.0 μM to 1.1 mM (R(2)=0.9958), with a calculated detection limit of 17.0 μM at a signal-to-noise ratio of 3. The low calculated apparent Michaelis-Menten constant (K(M)(app)) was 5.46 mM, implying the high enzymatic activity and affinity of immobilized GOD for glucose. It can reasonably be expected that this observation might hold true for other noble metal nanostructure-electroactive protein systems, providing a promising platform for the development of biosensors and biofuel cells.


FMR1 repeat sizes in the gray zone and high end of the normal range are associated with premature ovarian failure.
Premature ovarian failure (POF) is the occurrence of menopause before the age of 40 and affects 1% of the female population. Whereas the etiology of POF is largely unexplained, FMR1 premutation carriers are known to be at increased risk of POF compared with the general population. The FMR1 premutation alleles have 55-200 copies of a CGG repeat in the 5' untranslated region of the FMR1 gene. However, functional effects on gene expression may occur even for repeat sizes in what has been considered the "normal" range. To evaluate the role of the FMR1 repeat in POF, repeat sizes were examined in 53 women with idiopathic POF, 161 control women from the general population, and 21 women with proven fertility at an advanced maternal age. A significant increase in the number of FMR1 alleles between and including 35 and 54 CGG repeats was found in the POF patient population; 15 of 106 (14.2%) POF alleles were between and including 35 and 54 repeats, whereas only 21 of 322 (6.5%) alleles in the general population (P=0.02) and 2 of 42 (4.8%) alleles from women with proven late fertility (P=0.09) were of this size (P=0.01 versus combined controls). The effect was also significant for comparisons of genotype repeat size (repeat size weighted by the relative activity of the two FMR1 alleles) and biallelic mean (average size of the two alleles). These results are clinically relevant and suggest that the FMR1 gene plays a more significant role in the incidence of POF than has previously been thought.


[Minimally invasive, safe treatment of the neurogenic bladder with botulinum-A-toxin in children with myelomeningocele].
The efficacy and durability of botulinum-A toxin in the treatment of detrusor hyperreflexia in myelomeningocele (MMC) children was evaluated prospectively. A total of 15 children (10 male and 5 female, mean age 5.8 years), all on clean intermittent catheterisation (CIC) due to MMC, were "non responders" to orally and intravesically administered anticholinergic medication. Pretreatment assessment included a videourodynamic evaluation, incontinence scoring and a mercaptoacetyltriglycine-3 renal scan. We injected from 10 U/kg up to a maximum of 360 U botulinum-A toxin at 25-40 sites of the detrusor, sparing the trigone. Follow-up was 24 months. All children had a urodynamic reevaluation with assessment of bladder capacity and incontinence score at 3, 9 and 12 months. Mean bladder reflex volume increased from 72.00 +/- 28.12 ml to 298 +/- 32.45 ml (p < 0.001). The maximal detrusor pressure decreased from 78.76 +/- 23.14 cm H(2)O to 42.76 +/- 24.34 cm H(2)O (p < 0.001). Maximal bladder capacity increased from 136.34 +/- 45.71 ml to 297.02 +/- 87.17 ml (p < 0.001). Detrusor compliance increased from 18.29 +/- 27.19 ml/cm H(2)O to 51.17 +/- 38.17 ml/mmH(2)O (p < 0.001). While 10 patients became completely dry between CIC, the remaining 2 patients improved from score 3 to 1. Results at 9 months were similar to the ones at 3 months. The mean efficacy and durability of the toxin was 10.5 months after the first intravesical injection. Botulinum-A toxin is a safe alternative in the management of detrusor hyperreflexia in MMC children. Preliminary results are promising concerning urodynamic parameters and continence.


Are leukotrienes involved in human uterine contractility?
The effects of leukotrienes (LT) on the contractility of human and rat myometrial strips in vitro were compared with the effects of prostaglandins (PGs) and oxytocin. Preparations of human myometrial membranes were investigated for the presence and characteristics of LTC4 receptors. Neither the peptido-leukotrienes (LTC4, LTD4, LTE4) nor LTB4 had any consistent effect, stimulatory or inhibitory, on human pregnant or non-pregnant myometrium, at doses up to 1.25 microM; nor did they have any effect in rat non-pregnant myometrium. As expected, PGE2, PGF2 alpha (0.3 microM) and oxytocin (5 nM) stimulated human pregnant myometrium. PGF2 alpha stimulated and PGE2 inhibited human non-pregnant myometrium but oxytocin had no effect; all three compounds stimulated rat non-pregnant myometrium. The binding of 3H-LTC4 to human myometrium was specific (LTC4 greater than LTD4 much greater than LTE4, LTB4, PGE2, PGF2 alpha, arachidonic acid) but of low affinity compared with the binding of 3H-PGE2 to the same membrane preparations. These data support the view that leukotrienes have little direct influence on myometrial contractility.


Practical considerations regarding the use of genotype and pedigree data to model relatedness in the context of genome-wide association studies.
Genome-wide association studies of complex traits often are complicated by relatedness among individuals. Ignoring or inappropriately accounting for relatedness often results in inflated type I error rates. Either genotype or pedigree data can be used to estimate relatedness for use in mixed-models when undertaking quantitative trait locus mapping. We performed simulations to investigate methods for controlling type I error and optimizing power considering both full and partial pedigrees and, similarly, both sparse and dense marker coverage; we also examined real data sets. (1) When marker density was low, estimating relatedness by genotype data alone failed to control the type I error rate; (2) this was resolved by combining both genotype and pedigree data. (3) When sufficiently dense marker data were used to estimate relatedness, type I error was well controlled and power increased; however, (4) this was only true when the relatedness was estimated using genotype data that excluded genotypes on the chromosome currently being scanned for a quantitative trait locus.


A detailed genetic map of the chromosome 7 bronchial hyper-responsiveness locus.
Non-specific bronchial hyper-responsiveness to various inhaled stimuli is a characteristic of asthma. We have previously shown linkage of bronchial responsiveness to methacholine (measured as dose-response slope (DRS)) and the peripheral blood eosinophil count (EOS) to chromosome 7. We have now further investigated these linkages by genotyping 49 microsatellite markers across the DRS locus on chromosome 7. The markers were spaced on average 2.6 cM apart and spanned a sex averaged cumulative genetic distance of 129 cM. Multipoint linkage to DRS was bimodal and dipped at the centromere. The two peaks of linkage were close to markers D7S484 (P=0.0003) and D7S669 (P=0.006) respectively. Separate testing for linkage to paternally and maternally derived alleles showed that the linkage near D7S484 was paternally derived (P<0.00001): maternally derived alleles did not exhibit significant linkage. The results indicate that two disparate loci may be influencing asthma from chromosome 7.


RAS Mutation Conversion in Bevacizumab-Treated Metastatic Colorectal Cancer Patients: A Liquid Biopsy Based Study.
Liquid biopsies have shown that, in RAS mutant colorectal cancer, the conversion to RAS wild-type * status during the course of the disease is a frequent event, supporting the concept that the evolutionary landscape of colorectal cancer can lead to an unexpected negative selection of RAS mutant clones. The aim of the present study was to clarify whether the negative selection of RAS mutation in plasma might be drug-dependent. For this purpose, we used liquid biopsy to compare the rate of conversion from RAS mutant to RAS wild-type * in two groups of originally RAS mutant mCRC patients: the first treated with chemotherapy alone, while the second was treated with chemotherapy combined with bevacizumab. Serial liquid biopsies were performed at 3 months (T1), 6 months (T2), 9 months (T3), and 12 months (T4) after starting first line treatments. We found that the only independent variable significantly associated to RAS status conversion was the use of bevacizumab. RAS conversion was not found associated to tumor burden reduction, although bevacizumab-treated patients who converted to RAS wild-type * had a significantly longer PFS compared to patients who remained RAS mutant. The appearance of a "RAS wild-type * window", mainly in bevacizumab-treated patients, might present them as candidates for second line treatment with anti-EGFR, which was otherwise precluded.


Outbreaks of gastroenteritis that occurred during school excursions in Korea were associated with several waterborne strains of norovirus.
In May 2004, 97 of 309 (31%) and 97 of 207 (47%) school students from geographically distant areas were affected by acute gastroenteritis during excursions to neighboring hotels. The two hotels were 300 m apart, on Jeju Island, South Korea. Several strains of norovirus, including both genogroup I and genogroup II viruses, were identified in stool samples from the students and food handlers and in groundwater from the hotels. Of these several strains of norovirus, the nucleotide sequences for one strain were identical for samples from the students, food handlers, and groundwater.


Genotyping: a new application for the spent dialysate in peritoneal dialysis.
The dialysate of patients on peritoneal dialysis (PD) is used to determine the concentration of growth factors and cytokines, and as a source of resident peritoneal cells for subsequent culture experiments. We hypothesized that the cells contained in spent dialysate samples obtained at the time of the peritoneal equilibration test (PET) and subsequently stored may represent a source of DNA from a given PD patient. We characterized a protocol of DNA extraction from dialysates obtained in PD patients after a long dwell during the initial PET and kept frozen up to several years. After amplification of the source DNA by strand displacement using the bacteriophage phi 29 DNA polymerase, we performed polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis for the Glu298Asp polymorphism of ENOS to demonstrate the suitability of the extracted DNA for genotyping. A significant amount of DNA (mean yield 12 microg/ml dialysate) was extracted from frozen dialysate samples. The extraction yield was not influenced by the duration of storage at -20 degrees C. Following amplification, the DNA extracted from the dialysate was used successfully for genotyping the Glu298Asp polymorphism of ENOS, as demonstrated by parallel analyses using DNA extracted from the peripheral blood and sequencing. These results demonstrate that the dialysis effluent obtained at the time of the initial PET and stored at -20 degrees C is a reliable source of DNA that can be used subsequently for PCR amplification, RFLP analysis and sequencing.


Leguminosae in the diet: the raffinose-stachyose question.
Adhering to a galactose-free diet by strictly avoiding dairy products and known hidden sources of galac-tose does not completely normalize galactose-1-phosphate (gal-1-P) in erythrocytes from patients with galactosemia. Major neurological complications, even in the best treated patients, are threatening a good clinical outcome and dictate a continuous search for leaks in the dietary regimen. Raffinose and stachyose, present in important amounts in various vegetables, contain alpha-1,4 linked galactose which is cleaved only by bacterial alpha-galactosidases, presumably in the lower part of the gut. In order to test the hypothesis whether galactose released from raffinose and stachyose could be a source of absorbed galactose and a cause of elevated gal-1-P six patients with galactosemia (aged 6-24 years), underwent a raffinose- and stachyose-poor dietary regimen for 2 weeks. Before, after, and during the test period, the daily intake of stachyose and raffinose as well of protein, carbohydrate, fat and minerals was calculated from food protocols obtained from the patients. Plasma galactose and erythrocyte gal-1-P were measured at the end of the three test phases. Stachyose and raffinose intake was reduced to 5%-10% during the experimental diet, which was well tolerated, except for constipation in some patients. In five of the six patients gal-1-P in erythrocytes was somewhat lower (statistically not significant) during the test phase than during regular diet while plasma galactose remained unchanged. Galactose released from raffinose and stachyose may be absorbed and contribute to elevated gal-1-P values in erythrocytes of galactosemic patients.


Thyroid dysfunction in a prospectively followed series of patients with progressive systemic sclerosis.
Thirty-nine patients with progressive systemic sclerosis (PSS) in stable clinical conditions were extensively evaluated for the presence of thyroid disease. Two patients had previously undetected hypothyroidism while 7 additional patients had normal serum thyroid hormone levels but an exaggerated TSH response to thyrotropin-releasing hormone (TRH) administration, consistent with subclinical hypothyroidism. Four of the 9 subjects with abnormal TRH responses had positive antithyroid antibodies and of the remaining 5, 4 had been on chlorambucil or prednisone. Basal TSH and TSH response to TRH were significantly higher in PSS patients as a group when compared to a control group and increased with increasing duration of PSS. Serum antithyroid antibodies (antithyroglobulin and/or antimicrosomal antibodies) were positive in 18% and thyroid scans were abnormal in 18% of the patients. The euthyroid sick syndrome was not seen. Our findings indicate an increased frequency of, sometimes previously unsuspected, clinical and subclinical hypothyroidism in stable PSS patients which appears to be autoimmune in nature and becomes more prevalent with increased PSS duration. Careful and regular monitoring of the thyroid function in PSS patients is advisable.


Effects of afterload reduction (diuretics and vasodilators) on left ventricular volume and mitral regurgitation in severe congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.
The mechanism by which afterload reduction increases left ventricular stroke volume while decreasing left ventricular filling pressure has not previously been established. In 15 patients with severe congestive heart failure due to ischemic or idiopathic dilated cardiomyopathy, absolute ventricular volume, ejection fraction and total stroke volume from radionuclide ventriculography were compared with thermodilution stroke volume before and after intensive afterload reduction with vasodilators and diuretics titrated to hemodynamic goals. After 48 to 72 hours, pulmonary artery wedge pressure decreased from 32 +/- 8 to 16 +/- 4 mm Hg and systemic vascular resistance from 1,960 +/- 700 to 1,200 +/- 400 dynes s cm-5. End-diastolic volume decreased from 390 +/- 138 to 301 +/- 126 ml (p less than 0.01) and end-systolic volume from 316 +/- 127 to 241 +/- 111 (p less than 0.01). Ejection fraction did not change and total stroke volume decreased from 74 +/- 22 to 59 +/- 20 ml (p less than 0.01). Simultaneous forward stroke volume by thermodilution increased from 37 +/- 14 to 52 +/- 14 ml (p less than 0.01), and forward fraction increased from 0.55 +/- 0.40 to 0.96 +/- 0.42. Intensive reduction of ventricular filling pressure and systemic vascular resistance decreased total ventricular stroke volume by 20% but increased forward stroke volume by 40%. The major effect of intensive afterload reduction for severe congestive heart failure may be the reduction of ventricular volume and mitral regurgitation.


The role of stimulus preexposure in problem solving by Octopus vulgaris.
Octopus vulgaris is able to open transparent glass jars closed with plastic plugs and containing live crabs. The decrease in performance times for removing the plug and seizing the prey with increasing experience of the task has been taken to indicate learning. However, octopuses' attack behaviors are typically slow and variable in novel environmental situations. In this study the role of preexposure to selected features of the problem-solving context was investigated. Although octopuses failed to benefit from greater familiarity with the training context or with selected elements of the task of solving the jar problem, the methodological strategies used are instructive in potentially clarifying the role of complex problem-solving behaviors in this species including stimulus preexposure and social learning.


Electroanalytical approaches to understanding benzene metabolism.
Electrochemical techniques are ideally suited to the study of the metabolism of aromatic xenobiotics because the metabolites are frequently easier to oxidize than the parent compounds. In many cases, the trace metabolites have the lowest oxidation potentials and hence electrochemical methods have the greatest selectivity for these compounds. The sensitivity of dual-electrode liquid chromatography-electrochemistry for the detection and identification of trace metabolites was demonstrated by the detection of the secondary metabolite, hydroquinone, in a microsomal incubation containing benzene and ascorbic acid. The use of an electrochemical detector in a series configuration provides increased selectivity for chemically reversible metabolites such as hydroquinone. Electrochemical methods can also be used to generate metabolites. The products of the electrochemical oxidation of phenol and biphenol are compared with those generated in a peroxidase incubation.


ProMiR II: a web server for the probabilistic prediction of clustered, nonclustered, conserved and nonconserved microRNAs.
ProMiR is a web-based service for the prediction of potential microRNAs (miRNAs) in a query sequence of 60-150 nt, using a probabilistic colearning model. Identification of miRNAs requires a computational method to predict clustered and nonclustered, conserved and nonconserved miRNAs in various species. Here we present an improved version of ProMiR for identifying new clusters near known or unknown miRNAs. This new version, ProMiR II, integrates additional evidence, such as free energy data, G/C ratio, conservation score and entropy of candidate sequences, for more controllable prediction of miRNAs in mouse and human genomes. It also provides a wider range of services, e.g. the prediction of miRNA genes in long nonrelated sequences such as viral genomes. Importantly, we have validated this method using several case studies. All data used in ProMiR II are structured in the MySQL database for efficient analysis. The ProMiR II web server is available at http://cbit.snu.ac.kr/~ProMiR2/.


An analysis of the negative inotropic action of somatostatin.
1 Somatostatin (SS) was evaluated as a chronotropic and inotropic agent in isolated spontaneously beating auricles of rats, rabbits and guinea-pigs.2 SS was completely inactive in rat and rabbit auricles but exerted a dose-dependent, negative inotropic effect in guinea-pig auricles in concentrations between 1.5 x 10(-8) to 1.2 x 10(-6) M.3 The negative inotropic effect of SS (6.0 x 10(-8) and 3.0 x 10(-7) M) was not inhibited by a mixture of antagonists containing practolol (7.9 x 10(-6) M), phentolamine (3.5 x 10(-7) M), methysergide (2.8 x 10(-7) M), diphenhydramine (3.9 x 10(-5) M), cimetidine (4.0 x 10(-5) M) atropine (3.4 x 10(-7) M) and indomethacin (1.4 x 10(-5) M).4 The negative inotropic effect of SS was greatly potentiated by reduction in the Ca(2+) concentration of the medium from 5.0 to 1.25 mM.5 On a molar basis, SS was equipotent with acetylcholine (ACh) as a negative inotropic agent in the guinea-pig auricles.6 SS (6.0 x 10(-8) and 6.0 x 10(-7) M) was found to inhibit selectively the positive inotropic action of neurotensin (NT) in guinea-pig but not in rat auricles.7 The inhibitory action of SS against NT was independent of its negative inotropic action.8 These results suggest that SS produces its negative inotropic action by interacting with specific receptors presumably located in the cell membrane of guinea-pig atria. The interaction between SS and its receptor may cause a decreased Ca(2+) diffusion and/or transport into the atrial cells. The physiological and pharmacological significance of these results is discussed.


Surgical anatomy of the human middle ear: an insight into cochlear implant surgery.
This research was designed to aid practical otologic studies of the human middle ear. The topographic anatomy access of the middle ear was described with special focus to the cochlear implant procedure. It was conducted in an attempt to elucidate factors that would ultimately determine the ease of insertion of an electrode array. Fifteen right and 12 left temporal bones were dissected under the surgical microscope. After performing appropriate incisions, the distances between the stapedius muscle tendon, incus long crus and the cochleostomy were measured with the help of a digital microscope (Dino-Lite plus(®)). After performing statistical analysis, we found that strong relationship exists in the distances between the measured anatomical landmarks. Microscopic anatomical studies of the temporal bone are essential to safely perform surgical intervention within the middle ear. The results shows that morphometric data concerning different anatomical structures inside the middle ear, particularly distances, is an important contribution towards the planning of safe surgical procedures.


Prospective association between depressive symptoms and stroke risk among middle-aged and older Chinese.
This study aimed to assess the association between baseline symptoms and changes in depressive symptoms and stroke incidents. We used data from the Chinese Health and Retirement Longitudinal Study conducted in 2013, 2015, and 2018. In total, 10,100 individuals aged ≥45 years and without a history of stroke in 2013 were included. Depressive symptoms were measured using the 10-item version of the Center for Epidemiological Studied Depression scale (elevated depressive symptoms cutoff ≥10). Changes of depressive symptoms were assessed by two successive surveys (stable low/no, recent onset, recently remitted, and stable high depressive symptoms). We assessed whether baseline depressive symptoms and changes of them were associated with stroke incidents reported through 2018. Logistic regression analyses adjusted for age, gender, education, marital status and other potential confounders were performed. For the analysis of baseline depressive symptoms and stroke (n = 10,100), 545 (5.4%) reported stroke incidents in the following 5-year period. Individuals with elevated depressive symptoms in 2013 experienced a markedly higher stroke risk (odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.28-1.84) compared with those without elevated depressive symptoms. In the analysis of changes in depressive symptoms (n = 8491, 430 (5.1%) stroke events), participants with stable high (OR = 2.01, 95% CI = 1.58-2.56) and recent-onset (OR = 1.39, 95% CI = 1.04-1.85) depressive symptoms presented higher stroke risk compared to those with stable low/no depressive symptoms, while recently remitted symptoms (OR = 1.12, 95% CI = 0.80-1.57) were not associated with stroke risk. In conclusion, stable high and newly started depressive symptoms were associated with increased stroke risk, whereas the improvement of depressive symptoms was not related to increase in stroke risk, suggesting that stroke risk may be decreased by effective management of depressive symptoms.


Peripheral blood mononuclear cell DNA 6-thioguanine metabolite levels correlate with decreased interferon-gamma production in patients with Crohn's disease on AZA therapy.
6-Mercaptopurine (6-MP) and its prodrug azathioprine (AZA) are well known for their lymphocytotoxic and bone marrow suppressive effects in the management of patients with leukemia. Although their immunosuppressive properties are mediated by the active AZA antimetabolite 6-thioguanine (6-TG), its mechanism of action is largely unknown. In IBD, a significant inverse correlation has been shown between erythrocyte 6-TG metabolite levels and disease activity, further supporting the proposed immunosuppressive role for 6-TG. Since leukocytes possess quantitatively different purine metabolic pathways compared to erythrocytes, this study aims to measure lymphocyte DNA 6-TG metabolites and correlate levels with the INF-gamma and IL-10 cytokine profile in patients with Crohn's disease (CD). Forty-six adult patients with CD, either naive (17) or on long-term (>4-month) AZA therapy (29), had erythrocyte and lymphocyte DNA 6-TG levels measured by reverse-phase HPLC under UV detection (6-TG, 340 nm). Lymphocyte DNA 6-TG was expressed as picomoles per milligram of DNA. Lymphocyte DNA 6-TG metabolite levels were correlated with INF-gamma and IL-10 cytokine profiles using the OptEIA kit (Pharmigen). Lymphocyte DNA 6-TG metabolite levels correlate with erythrocyte 6-TG levels (P < 0.03) but not total patient leukocyte levels. Erythrocyte 6-TG metabolite levels correlated (P < 0.01) inversely with INF-gamma but not IL-10 cytokine levels. This study suggests a preferential dampening of the TH1 response on exposure to 6-TG and a possible immunosuppressive mechanism of action for AZA. Future studies are needed to determine if cytokine profiles can be used to predict recalcitrant CD to AZA therapy.


A role of peptidergic nerves in the internal anal sphincter of Hirschsprung's disease.
It is not clear what contribution the internal anal sphincter makes to the impaired motility observed in patients with Hirschsprung's disease (HD). Neuropeptides have recently been shown to be neurotransmitters in the nonadrenergic, noncholinergic inhibitory and excitatory nerves in the human gut. To clarify the physiologic significance of vasoactive intestinal polypeptide and substance P in the internal anal sphincter of HD (aganglionosis), we investigated the enteric nerve responses on lesional and normal internal anal sphincter muscle strips above the dentate line. The lesional and normal internal anal sphincter muscle strips above the dentate line were derived from patient with HD (9 cases) and patients who underwent rectal amputation for low rectal cancers (8 cases). A mechanographic technique was used to evaluate in vitro muscle responses to these peptides of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. Nonadrenergic, noncholinergic inhibitory nerves were found to act on the normal internal anal sphincter but had no effect on the enteric nerves in aganglionosis. Peptidergic (vasoactive intestinal polypeptide and substance P) nerves were found to act on normal colon, but no effect was observed in the aganglionic internal anal sphincter. These findings suggest that peptidergic nerves play an important role in the impaired motility observed in the internal anal sphincter with HD.


Astrocyte-neurone communication following oxygen-glucose deprivation.
We looked at the possible interactions between astrocytes and neurones during reperfusion using an in vitro model of ischaemia-reperfusion injury, as a controlled environment that lends itself easily to manipulation of the numerous variables involved in such an insult. We constructed a chamber in which O2 can be lowered to a concentration of 1 microm and developed a primary cortical neuronal culture that is 99% pure and can survive to at least 10 days in vitro. We also established a novel system for the co-culture of astrocytes and neurones in order to study the communication between these cells in a manner that allows the complete separation of one cell type from another. Neurone cultures showed profound cell death following an ischaemic period of only 15 min. We co-cultured neurones that had been subjected to a 15-min ischaemic insult with either non-insulted astrocytes or astrocyte-conditioned medium during the reperfusion stage. Both astrocytes and astrocyte-conditioned medium enhanced neuronal survival. Our data also suggest that astrocyte-sourced neuronal glutathione synthesis may play a role in preventing neuronal death.


A morphologic and histochemical study of metaplastic polyps of the colorectum.
A combined morphologic and histochemical study of metaplastic polyps of the colorectum was undertaken. With increasing size, these lesions showed alterations in architecture and differentiation, increased secretion of carcinoembryonic antigen and a reduced secretion of O-acylated sialomucin. These functional changes are also observed in colorectal cancers, but not in tubular adenomas showing low-grade dysplasia. Since there is little clinical evidence for a metaplastic polyp-carcinoma sequence, it is suggested that the sets of factors which lead to adenoma and metaplastic polyp formation in the colorectum are both required to induce malignant transformation.


["Denta-Solar"--clinical study of new toothbrush with integrated TiO2 semi-conductor].
The aim of this work is to answer the question as to whether the TiO2 semiconductor integrated into the toothbrush "Denta-Sola" has any effect on the removal of plaque. The clinical study shows that the Silness/Löe and Quigley/Hein plaque indices improved when the "Denta-Solar" was used over a four-week study period, whereas they deteriorated when the toothbrush was used without the semiconductor.


An anticipatory geriatric strategy: to better care for those americans not yet old.
Current US public policy decisions will have impact on national plans to care for the aging American baby boomer population over the next several decades. The recent health care legislative debate has been largely about the structure of health care for those still too young to be covered by Medicare, but the legislation may have important implications for the average rates of accumulating chronic illness and disability in midlife and influence the care needs for that cohort of individuals even after they become elderly.


MDS/AML with del5q: An acquired "laminopathy"?
In this issue of Cell Stem Cell, Reilly et al. propose loss of LMNB1, the gene encoding lamin B1, often deleted in MDS/AML, as a novel genetic basis for the abnormal nuclear shape of neutrophils (known as acquired Pelger-Huët anomaly) and a cause of HSPC fate alterations promoting malignancy.


[The Baker's cyst - a blunt sword of Damokles in radiosynoviorthesis (RSO)?]
The existence of a popliteal Baker's cyst was regarded as a contraindication for radiosynoviorthesis of the knee joint since decades. A so-called "ventile mechanism" was discussed leading to a significant concentration of the intraarticularly applied, high energy beta emitting radiopharmaceutical yttrium-90-colloid in the cyst. This cyst arises from a bursa beneath the tendon of the medial head of the gastrocnemius muscle, normally communicating with the knee joint space. Since the cyst wall is much thinner than the knee joint capsule, a radiogenic rupture of the cyst was feared, leading to severe radiogenic necroses of the surrounding soft tissue. Due to this potential hazard, knee joint ultrasound is mandatory prior to radiosynoviorthesis to check for any popliteal cysts. New studies however decline the risk of a radiogenic cyst rupture after an appropriately performed radiosynoviorthesis of the knee joint.In case of a preexistent cyst rupture, the risk of a radiogenic tissue damage remains an issue and magnetic resonance imaging (MRI) is the method of choice to exclude this potential hazard. However, MRI sometimes leads to equivocal results. Scintigraphy of the knee joint after intraarticular application of Tc-99m-nanocolloid offers the possibility to check for the integrity of the Baker's cyst in these patients to be sure that radiosynoviorthesis will not lead to a relevant extraarticular leakage with soft tissue necroses. This study describes the procedure of intracavitary distribution scintigraphy by means of representative case reports.


Effect of photoperiodicity and methods of follicular wave emergence on follicle turn-over, recovery and quality of oocytes, and early in-vitro developmental competence of embryos using ovum pick-up in Nili-Ravi buffaloes: Preliminary evidence.
The objectives of the present study were to evaluate the effects of photoperiodicity, gauge (G) of ovum pick-up (OPU) needle, and two methods of follicular wave emergence on follicular turn-over, oocyte recovery (OR), quality of the oocytes (OQ), and early in-vitro developmental competence of embryos in Nili-Ravi buffaloes (n = 20). In 1st experiment, buffaloes (n = 12; 4 buffaloes/season) were randomly assigned to optimize the OPU's (n) either with 17 G or 18 G needle in one of the following seasons: 1) peak breeding season (PBS; Sep-Nov; n = 31), 2) transition breeding season (TBS; Dec-Feb; n = 32), and 3) low breeding season (LBS; Apr-June; n = 32). During 2nd experiment, buffaloes (n = 8) were enrolled randomly in a 2 × 2 cross-over design to compare the two methods of wave emergence either using follicular ablation (FA; n = 4), or synchronization protocol (CIDR-EB; n = 4) during PBS. In FA method, the ovarian follicles were aspirated (week -1), and subsequently repeated OPU's (n = 55) were performed for 7 weeks. However, in CIDR-EB synchronized buffaloes, a progesterone device (CIDR) was inserted in the anterior vagina and a single dose of estradiol benzoate (2 mg) and prostaglandin (150 μg) were administered i.m. on d 1. The CIDR was removed on d 7 and repeated OPU's (n = 56) were performed. In both experiments, a 7-d resting period was provided between each OPU session. Data on the follicular turn-over, OR, OQ, and early stages of embryonic development were analyzed with mixed models using the PROC MIXED and GLIMMIX procedures of SAS. Results revealed that the number of medium sized follicles (LSM ± SEM) and rate of OR (%) were greater (P < 0.05) during PBS (2.76 ± 0.40; 61%) and TBS (1.73 ± 0.30; 54%) as compared to LBS (0.68 ± 0.30; 31%) in buffaloes, respectively. The OR rate was also greater (P < 0.05) using 17 G as opposed to 18 G needle (62% vs. 35%), however, there was no effect (P > 0.05) of season and G of needle on OQ in buffaloes. In experiment 2, the number of small (3.50 ± 0.63 vs.2.69 ± 0.60) sized follicles was higher (P < 0.05) in FA, whereas, medium (1.13 ± 0.45 vs. 1.59 ± 0.45) sized follicles were greater (P < 0.05) in CIDR-EB synchronized buffaloes. The OR rate (67% vs. 53%), and OQ (Grade I_+_II; 15% vs. 16% and Grade III_+_IV; 85% vs. 84%), remained similar (P > 0.05) in FA and CIDR-EB treated buffaloes, respectively. Similarly, rates of in-vitro maturation (66% vs. 59%), cleavage (42% vs. 53%), 4-cell (27% vs. 32%), 8-cell staged embryos (23% vs. 25%), and morula (13% vs. 8%) did not differ (P > 0.05) between FA and CIDR-EB methods of follicular wave emergence, respectively. Taken together, it is concluded that peak or transition breeding seasons are suitable to perform OPU using 17 G needle for maximum follicular turn-over, and OR in buffaloes. However, the two fundamental methods of synchronization of wave emergence resulted in similar efficiency for OPU derived in-vitro embryo production in Nili-Ravi buffaloes.


Significant impairment of intestinal health in zebrafish after subchronic exposure to methylparaben.
Methylparaben (MeP) is a ubiquitous pollutant in aquatic environment, which has caused severe pollution worldwide. However, aquatic toxicology of MeP is still largely unknown. In the present study, adult zebrafish were exposed to environmentally realistic concentrations of MeP (0, 1, 3, and 10 μg/L) for 28 days. In terms of the antimicrobial nature, dysregulation of gut microbiota and zebrafish health by MeP were elucidated after exposure. High-throughput amplicon sequencing showed that MeP subchronic exposure was able to disrupt the composition and diversity of gut microbial community, which was characterized by the alterations in alpha diversity and divergent distribution by principal component analysis. In addition, MeP exposure increased the body length and body weight of female fish, implying stimulated growth at low doses. In male intestine, consistent increases were notable in goblet cell density, tight junction protein (TJP) 2 expression, and serotonin neurotransmitter concentration after MeP exposure. In contrast, female intestine exposed to MeP had lower density of goblet cells, inhibited expression of TJP2, reduced concentration of serotonin, but up-regulated transcription of pro-inflammatory cytokine. Under the stress of MeP pollutant, intestinal catalase antioxidant enzyme was activated, thus contributing to the removal of oxidative free radicals. Correlation analysis verified the modulation of TJP2 expression by Lactobacillus probiotic bacteria. Disturbances in goblet cell, tight junctions, and serotonin by MeP may be combined to interfere with gut barrier function. Overall, the present study highlights the impairment of intestinal health by environmentally realistic concentrations of MeP, which necessitates an urgent risk assessment.


Investigation into the trophic transfer and acute toxicity of phosphorus-based nano-agromaterials in Caenorhabditis elegans.
Biogenic phosphorus (P) based - nanomaterials (NMs) are currently being explored as nanofertilizers. In this study, the acute toxic effects and trophic transfer of multiple types of P-based NMs were examined on soil-dwelling nematode, Caenorhabditis elegans. The study involved four variants of nanohydroxyapatites (nHAPs) synthesized either via a biogenic or a chemical route and another NM, nanophosphorus (nP), biosynthesized from bulk rock phosphate (RP). The pristine NMs differed in their physicochemical properties with each possessing different shapes (biogenic nHAP: platelet-shaped, ˜35 nm; biogenic nP, ˜5-10 nm: dots; chemically synthesized nHAPs: spherical, ˜33 nm, rod, ˜80 nm and needle-shaped, ˜64 nm). The toxic effects of NMs' in C. elegans were assessed using survival, hatching and reproductive cycle as the key endpoints in comparison to bulk controls, calcium phosphate and RP. The interactions and potential uptake of fluorescent-tagged nHAP to E. coli OP50 and C. elegans were investigated using confocal microscopy. The transformation of NMs within the nematode gut was also explored using dynamic light scattering and electron microscopy. C. elegans exposed to all of the variants of nHAP and the nP had 88-100% survival and 82-100% hatch rates and insignificant effects on brood size as observed at the tested environmentally relevant concentrations ranging from 5 to 100 μg.mL-1. Confocal microscopy confirmed the interaction and binding of fluorescent-tagged nHAP with the surface of E. coli OP50 and their trophic transfer and internalization into C. elegans. Interestingly, there was only a small reduction in the hydrodynamic diameter of the nHAP after their uptake into C. elegans and the transformed NMs did not induce any additional toxicity as evident by healthy brood sizes after 72 h. This study provides key information about the environmental safety of agriculturally relevant P-based NMs on non-target species.


Mutation studies and structure-based identification of potential inhibitor molecules against periplasmic amino acid binding protein of Candidatus Liberibacter asiaticus (CLasTcyA).
Earlier reported crystal structure of CLasTcyA revealed unique features like relatively a larger substrate binding pocket, an extended C-terminal loop restricted by a disulfide bond and involvement of residues from hinge region in substrate binding. In present study, CLasTcyA mutants were created to evaluate the importance of these unique features through biophysical characterization. The Val58 in CLasTcyA was replaced by Trp, conserved in most cystine binding proteins, to reduce the size of the binding pocket. All other mutations were created in CLasTcyAV58W mutant as the presence of Trp could be used for intrinsic fluorescence studies. The CLasTcyAV58W showed a noticeable increase in binding affinity and thermal stability as compared to the native form. The mutation of two cysteines in triple mutant CLasTcyAV58W/C212S/C239S, removal of C-terminal extended loop in truncated CLasTcyAV58W/C212S and mutation of His95 from hinge region in the double mutant CLasTcyAV58W/H95A showed a marked decrease in stability-indicating the importance of the unique features in structure of CLasTcyA. The bioinformatics-based virtual screening was employed to screen the potential inhibitor molecules for detailed future studies. The results clearly establish the importance of unique features in structure-function relationship of CLasTcyA.


Is Friendship Network Weight Status Associated with One's Own Psychological Well-being? It Depends on One's Own Weight Status.
Drawing on multiple theoretical perspectives (e.g., social comparison theory, reward theory, evolutionary theory), the present research examined the relations of self and friendship network weight status to body satisfaction, self-esteem, and depression. A diverse, population-based sample of adolescents completed measures of well-being and were measured for height and weight. Boys had greater self-esteem if their male friendship networks' weight status mismatched, versus matched, their own weight status (d = .23). Conversely, boys had greater body satisfaction if their female friendship networks' weight status matched, versus mismatched, their own weight status (d = .18). For girls, the relations of male and female friendship networks' weight status with well-being did not vary by one's own weight status. Evolutionary theory appears to best explain the observed patter of results, and clinicians may want to consider friends' weight status when dealing with adolescents' body satisfaction issues.


Evaluation of health belief model-based educational intervention on colorectal cancer screening behavior at South Khorasan, Iran.
Colorectal cancer is the most common cancer of the gastrointestinal tract. Health beliefs play an important role in the development of health behaviors. In this study, the effect of educational intervention based on Health Belief Model on colorectal cancer screening behavior was investigated. This study was performed as a randomized controlled intervention. The study population was 50-70-years old in Khosf city. Initially, 120 eligible populations were randomly divided into intervention and control groups (60 people in each group). The data collection tool was a standard colorectal cancer screening questionnaire that was completed before, immediately, and 3 months after the intervention. The intervention consisted of eight 60-min training sessions. The collected data were analyzed using SPSS19 software and statistical tests. The mean age of the intervention and control groups was 63.53 ± 5.67 and 57.73 ± 5.77 years. In terms of mean scores of knowledge, perceived susceptibility, perceived severity, and perceived barriers were homogeneous before intervention. After the intervention, the mean score of the model constructs showed significant changes, which was statistically significant (P < 0.05). The rate of occult blood test in stool 3 months after training reached 90% in the intervention group and 15% in the control group. The results of this study showed that by taking measures to reduce perceived barriers as well as increase knowledge, perceived susceptibility, severity, benefits and self-efficacy, the rate of participation in occult blood testing in feces can be significantly increased.


The Role of Treatment Sequencing with Immune-Checkpoint Inhibitors and BRAF/MEK Inhibitors for Response and Survival of Patients with BRAFV600-Mutant Metastatic Melanoma-A Retrospective, Real-World Cohort Study.
The advent of immune-checkpoint inhibitors (CPI) and BRAF/MEK-directed targeted therapy (TT) has improved the treatment landscape of patients with BRAFV600-mutant metastatic melanoma. While TT allows for rapid disease control, the development of secondary TT resistance limits the duration of responses. Responses to CPI have a slower onset but can be durable in a subset of patients. To date, little prospective data is available for the optimal sequencing of these agents in melanoma patients. In this retrospective, single-center, real-world analysis, we identified 135 patients with BRAF-mutated, metastatic melanoma who received consecutive treatment with TT followed by CPI, or vice versa, as first and second-line therapy, respectively. We collected data on clinical-pathological factors, treatment duration, best overall response, progression-free survival and overall survival (OS). Our data revealed that front-line treatment with CPI, followed by TT, showed a non-significant trend towards better OS compared to front-line TT (median OS: 35.0 vs. 18.0 months, p = 0.070). This association was confirmed in a subgroup of patients without systemic pre-treatments (median OS: 41.0 vs. 14.0 months, p = 0.02). Further, we observed significantly better objective response rates to second-line treatments for patients receiving front-line CPI (18.4 vs. 37.8%, p = 0.024). Last, our results indicated that rapid disease progression was less common in patients treated with front-line CPI (27.6% vs. 16.2%) and that subsequent treatment with TT resulted in favorable survival outcomes. Our real-world data indicate that sequential treatment with front-line CPI is associated with favorable tumor control and overall survival in a subgroup of previously untreated BRAF-mutant metastatic melanoma patients.


Effects of phorbol esters and calcium ionophore on nonspecific cytotoxic cells.
In the present study mechanisms of signal transduction were investigated by treatment of NCC with phorbol esters and calcium ionophore. NCC were stimulated to produce 3-fold increased cytotoxicity by 10(-4) to 10(-5) M A23187. PMA, PDD, and 4-beta phorbol either suppressed NCC lysis (PMA) or had no enhancing effects (PDD and 4-beta). At a concentration of 10(-4) M increased cytotoxicity occurred after 0.5 to 3 hours treatment. Four-hour preincubation enhanced cytotoxicity at suboptimal A23187 concentrations. A23187 produced increased NCC activity at each E:T ratio tested, however, greatest differences in A23187 concentrations were observed at 20:1 and 40:1. The effects of simultaneous treatment of NCC and/or sequential with PMA and A23187 indicated that different transduction pathways might operate to augment cytotoxicity. PMA, 10(-8) M, combined with 10(-4) M concentrations of A23187 produced a 164.7% increase in cytotoxicity compared to media controls, and a 37.7% increase compared to A23187 controls. These data indicate that teleost cytotoxic cells, unlike mammalian NK, are augmentable by increased levels of extracellular calcium without the presence of any other comodulating signals.


NK cells are dysfunctional in human chronic myelogenous leukemia before and on imatinib treatment and in BCR-ABL-positive mice.
Although BCR-ABL+ stem cells in chronic myeloid leukemia (CML) resist elimination by targeted pharmacotherapy in most patients, immunological graft-versus-leukemia effects can cure the disease. Besides cytotoxic T cells, natural killer (NK) cells may have a role in immune control of CML. Here, we explored the functionality of NK cells in CML patients and in a transgenic inducible BCR-ABL mouse model. Compared with controls, NK-cell proportions among lymphocytes were decreased at diagnosis of CML and did not recover during imatinib-induced remission for 10-34 months. Functional experiments revealed limited in vitro expansion of NK cells from CML patients and a reduced degranulation response to K562 target cells both at diagnosis and during imatinib therapy. Consistent with the results in human CML, relative numbers of NK1.1+ NK cells were reduced following induction of BCR-ABL expression in mice, and the defects persisted after BCR-ABL reversion. Moreover, target-induced degranulation by expanded BCR-ABL+ NK cells was compromised. We conclude that CML is associated with quantitative and functional defects within the NK-cell compartment, which is reproduced by induced BCR-ABL expression in mice. Further work will aim at identifying the mechanisms of NK-cell deficiency in CML and at developing strategies to exploit NK cells for immunotherapy.


Antithyroglobulin Antibody Variation During Follow-Up Has a Good Prognostic Value for Preoperative Antithyroglobulin Antibody-Positive Differentiated Thyroid Cancer Patients: A Retrospective Study in Southwest China.
Antithyroglobulin antibody (TgAb) is a potential tumour marker for detecting differentiated thyroid cancer (DTC) recurrence, but insufficient data have supported its clinical applications. Our study aimed to describe the changing trend of TgAb after surgery and identify the relationship between this trend and clinical outcomes. We reviewed the electronic records of 1,686 DTC patients who had undergone total thyroidectomy (TT) and radioactive iodine (131I) therapy at West China Hospital of Sichuan University from January 2015 to December 2017. Finally, 289 preoperative TgAb-positive DTC patients were included and divided into four subgroups depending on the clinical outcome: Group A (tumour free), Group B (uncertain), Group C (incomplete biochemical response), and Group D (structural disease). The patient demographics, tumour characteristics, operations, pathology reports, and all serological biomarkers were reviewed and compared, and the prognostic efficacy of TgAb was evaluated. Among all 1,686 patients, 393 (23.65%) were TgAb positive (>40 IU/ml) preoperatively. The TgAb level in Group A decreased significantly after surgery and 131I therapy and stabilised at a low level after 1-2 years of 131I therapy. However, in the other three groups, the decrease in TgAb was not significant after treatment. Conversely, TgAb declined slowly and remained stable or increased. The variations in TgAb relative to the preoperative level of Group A were significantly larger than those of Groups B, C, and D at most time points of follow-up (p < 0.001). By receiver operating characteristic (ROC) analyses, the variations of TgAb > -77.9% at 6 months after 131I therapy (area under the curve (AUC) = 0.862; p < 0.001) and TgAb > -88.6% at 2 years after 131I therapy (AUC = 0.901; p < 0.001) had good prognostic efficacy in tumour-free survival. When the variation in TgAb > -88.6% at 2 years after 131I therapy was incorporated as a variable in the American Thyroid Association (ATA) categories, both intermediate- and high-risk patients also had a significantly increased chance of being tumour free (from 75.68% to 93.88% and 42.0% to 82.61%, respectively). For preoperative TgAb-positive DTC patients, variations in TgAb > -77.9% at 6 months after 131I therapy and TgAb > -88.6% at 2 years after 131I therapy had good prognostic efficacy. Their incorporation as variables in the ATA risk stratification system could more accurately predict disease-free survival.


Improving Awareness of Workplace Opioid Use and Addiction Prevention: A Train-the-Trainer Approach.
The National Institute of Environmental Health Sciences Worker Training Program developed instructor curriculum, a training tool, and materials to prepare trainees to conduct opioids workplace awareness training. Opioids and the Workplace Prevention and Response (OWPR) Train-the-Trainer (TTT) courses were held during three instructor-led online programs. The OWPR TTT was evaluated using an online pre- and posttest among registered participants, and an assessment of discussion among trainees during the training program. A total of 31 pretests and 24 posttests were completed for the three TTT courses conducted. Quantitative and qualitative data complemented each other in supporting the conclusion that the training achieved intended objectives. The evaluation illustrated that the training was effective in increasing knowledge and confidence in conducting awareness training on opioid use and addiction prevention.


Negative pressure wound therapy in elective stoma reversal surgery: results of a UK district general hospital pilot.
The role of negative pressure wound therapy in stoma reversal surgery remains unknown. To evaluate this, a retrospective, non-randomized, single-institution, pilot study was conducted. Surgeon preference determined type of wound closure and application of the single-brand negative wound pressure device. No patient in the intervention group suffered wound complications, but five of the thirty-six patients in the control group suffered surgical site infection-related complications. Primary closure and negative pressure wound therapy use decreases wound complications in stoma reversal surgery, thereby alleviating the wound-management burden in hospitals and in the community. This has cost-saving implications, but further studies are needed.


Psychometric Properties of the Farsi Version of Eyberg Child Behavior Inventory (F-ECBI) in Iranian Population.
Objective: Eyberg Child Behavior Inventory (ECBI) is one of the most frequently used tools for measuring behavioral problems; however, no research has been done to evaluate its psychometric properties in Iran. Method : The present study sought for exploring the factor structure and psychometric properties of the F-ECBI in an Iranian sample. A total of 495 mothers (mean age = 33.83 years; SD = 4.78) who reported behavioral problems in their children aged 3 to 12 years (mean age = 6.36 years; SD = 2.66) were selected via convenience sampling in 2018-2019. The psychometric properties of F-ECBI, including reliability (Cronbach's alpha) and validity (exploratory and confirmatory factor analysis, and convergent validity) were assessed using SPSS version 25 and LISREL 8.80. Results: By performing EFA on the first sample part (n = 360), the examination of scree plot supported a 3-factor or 4-factor solution, and pattern matrix resulted in a 3-factor structure. The factors were called as "behavioral problems related to oppositional defiant", "behavioral problems related to inattentive", and "behavioral problems related to conduct", according to their content and the research. CFA was performed on the second part of the sample (n = 135) to test the fitness of the 3-factor solution. According to CFI (0.91), NFI (0.91), NNFI (0.90), IFI (0.91), PNFI (0.77), GFI (0.75) AGFI (0.70), PGFI (0.62) and chi-square (540.31) indexes, the model had acceptable fitness. Cronbach's alpha was employed to measure the internal consistency and it revealed to be at a good to excellent level (behavioral problems related to oppositional defiant = 0.88; behavioral problems related to inattentive = 0.84; behavioral problems related to conduct = 0.74). The 3-factors subscales were associated with total difficulties, internalizing and externalizing SDQ, indicating the good convergent validity of F-ECBI. Conclusion: The F-ECBI has good psychometric properties in Iran and can be employed as a useful instrument for measuring children's behavioral problems.


The relative biological effectiveness of 100 kV X-rays determined by the V-79 cell colony assay.
The relative biological effectiveness (RBE) of 100 kV X-rays compared with cobalt-60-gamma-irradiation was determined using a cell colony assay based on the survival of Chinese hamster V-79 lung fibroblasts. The 37% dose (Do) was found to range from 1.12 to 1.47 and from 1.33 to 1.63 Gy for X-rays and 60Co-gamma-irradiation respectively. The mean RBE value calculated from the Do values was found to be 1.13 +/- 0.04. This figure compares favourably with RBE values calculated from Do values using other endpoints.


[Results of microsurgical lymphovenous anastomoses in lymphedema--report of 110 cases].
Between 1980 and 1986, 110 patients with lymphedema of the extremities (n = 98), male and female external genitalia (n = 9), breast (n = 2), and face (n = 1) were treated microsurgically. Microsurgery for primary (n = 6) and secondary (n = 104) lymphedema at present consists of anastomosis between collective lymphatics and veins. Ninety-eight patients with lymphedema of the extremities were followed-up for 26 months. The immediate and long-term results have been very satisfactory. Excellent and good results were obtained in 76.5%. An average reduction in circumference of the affected limb of 6.2 cm and an average reduction of excess volume of 59.2 +/- 29.5% (representing 703 +/- 850 ml) were obtained. These results prove that by standardized technique the microlymphaticovenous anastomoses can produce a good therapeutic result. On the basis of our clinical experience in treating lymphedema by microlymphaticovenous anastomoses, we believe that the anastomoses should be performed early and their number should be sufficiently high. Indications, types of procedures and advantages of the operation are presented.


Age-related histopathological and biochemical testicular damages were ameliorated by vitamin C administration.
Aging is an irreversible process associated with decreased biological functions that can lead to the reduction of reproductive organs capacities in males and females. Paternal age is a significant predictor of offspring health and development. So, the aim of this study was to evaluate the effects of vitamin C on histopathological and biochemical testicular changes following aging process with a focus on stereological methods. For this study, 48 adult male NMRI mice were divided into two control and experimental groups. Mice in experimental group were supplemented with vitamin C (150mg/kg) including 24-h interval by oral gavage for 33 weeks. Same regime was performed for animals in control group except that vitamin C was replaced by water. Then, right testes were extracted for stereological and left testes were used for molecular analyses on weeks 8, 12, and 33. Our findings showed low semen quality, decreased level of serum Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), and testosterone along with increased reactive oxygen species (ROS) production and higher apoptotic gene expression following aging. Stereological studies showed that the volume of testes, the length of seminiferous tubules, and the number of spermatogenic and none-spermatogenic cells decreased significantly during aging. Also, vitamin C consumption for 33 weeks significantly improved biochemical and histological indices. The impact of aging on male reproduction seems to be inevitable worldwide. Therefore, the use of protective and preventive remedies conserving male fecundity is very important and based on our results, vitamin C is a beneficial candidate for improving age-related testicular changes due to aging process.


TMEM16F mediated phosphatidylserine exposure and microparticle release on erythrocyte contribute to hypercoagulable state in hyperuricemia.
The link between hyperuricemia (HUA) and the risk of venous thromboembolism (VTE) has been well established. However, the mechanisms of thrombus generation and the effect of HUA on procoagulant activity (PCA) of erythrocytes remain unclear no matter in uremia or hyperuricemia. Here, phosphatidylserine (PS) exposure, microparticles (MPs) release, cytosolic Ca2+, TMEM16F expression, reactive oxygen species (ROS) and lipid peroxidation of erythrocyte were detected by flow cytometer. PCA was assessed by coagulation time, purified coagulation complex and fibrin production assays. The fibrin formation was observed by scanning electron microscopy (SEM). We found that PS exposure, MPs generation, TMEM16F expression and consequent PCA of erythrocyte in HUA patients significantly increased compared to those in healthy volunteers. Furthermore, high UA induced PS exposure, and MPs release of erythrocyte in concentration and time-dependent manners in vitro, which enhanced the PCA of erythrocyte and was inhibited by lactadherin, a PS inhibitor. Additionally, using SEM, we also observed compact fibrin clots with highly-branched networks and thin fibers supported by red blood cells (RBCs) and RBC-derived MPs (RMPs). Importantly, we demonstrated UA enhanced the production of ROS and lipid peroxidation and reduced the generation of glutathione (GSH) of erythrocyte, which enhanced TMEM16F activity and followed PS externalization and RMPs formation. Collectively, these results suggest that Ca2+-dependent TMEM16F activation may be responsible for UA-induced PS exposure and MPs release of RBC, which thereby contribute to the prothrombotic risk in HUA.


Chloroplasts: state of research and practical applications of plastome sequencing.
This review presents origins, structure and expression of chloroplast genomes. It also describes their sequencing, analysis and modification, focusing on potential practical uses and biggest challenges of chloroplast genome modification. During the evolution of eukaryotes, cyanobacteria are believed to have merged with host heterotrophic cell. Afterward, most of cyanobacterial genes from cyanobacteria were transferred to cell nucleus or lost in the process of endosymbiosis. As a result of these changes, a primary plastid was established. Nowadays, plastid genome (plastome) is almost always circular, has a size of 100-200 kbp (120-160 in land plants), and harbors 100-120 highly conserved unique genes. Plastids have their own gene expression system, which is similar to one of their cyanobacterial ancestors. Two different polymerases, plastid-derived PEP and nucleus-derived NEP, participate in transcription. Translation is similar to the one observed in cyanobacteria, but it also utilizes protein translation factors and positive regulatory mRNA elements absent from bacteria. Plastoms play an important role in genetic transformation. Transgenes are introduced into them either via gene gun (in undamaged tissues) or polyethylene glycol treatment (when protoplasts are targeted). Antibiotic resistance markers are the most common tool used for selection of transformed plants. In recent years, plastome transformation emerged as a promising alternative to nuclear transformation because of (1) high yield of target protein, (2) removing the risk of outcrossing with weeds, (3) lack of silencing mechanisms, and (4) ability to engineer the entire metabolic pathways rather than single gene traits. Currently, the main directions of such research regard: developing efficient enzyme, vaccine antigen, and biopharmaceutical protein production methods in plant cells and improving crops by increasing their resistance to a wide array of biotic and abiotic stresses. Because of that, the detailed knowledge of plastome structure and mechanism of functioning started to play a major role.


MMP3 activity rather than cortical stiffness determines NHE1-dependent invasiveness of melanoma cells.
Both cell adhesion and matrix metalloproteinase (MMP) activity depend on pH at the cell surface. By regulating extracellular juxtamembrane pH, the Na+/H+ exchanger NHE1 plays a significant part in human melanoma (MV3) cell migration and invasion. Because NHE1, besides its pH-regulatory transport function, also serves as a structural element tying the cortical actin cytoskeleton to the plasma membrane, we investigated whether NHE1 affects cortical stiffness of MV3 cells, and how this makes an impact on their invasiveness. NHE1 overexpressing MV3 cells were compared to the corresponding mock-transfected control cells. NHE1 expression was verified by Western blotting, cariporide (HOE642) was used to inhibit NHE1 activity, cell stiffness was determined by atomic force microscopy, and F-actin was visualized by phalloidin-staining. Migration on, and invasion of, native and glutaraldehyde-fixed collagen I substrates were analyzed using time-lapse video microscopy and Boyden-chamber assays, respectively. MMP secretion and activity were detected by Western blot and zymography, respectively. MMP activity was inhibited with NNGH. The cortical, but not the bulk stiffness, was significantly higher in NHE1 overexpressing cells. This increase in cortical stiffness was accompanied by a reorganization of the cortical cytoskeleton, i.e. a condensation of F-actin underneath and along the plasma membrane. However, it was not affected by NHE1 inhibition. Nevertheless, actin dynamics is required for cell invasion as demonstrated with the application of cytochalasin D. NHE1 overexpression was associated with an elevated MMP3 secretion and an increase in the invasion of a native matrix. This increase in invasiveness could be antagonized by the MMP inhibitor NNGH. Transmigration through a glutaraldehyde-fixed, indigestible substrate was not affected by NHE1 overexpression. NHE1, as a structural element and independently of its transport activity, contributes to the organization of the cortical F-actin meshwork and thus impacts cortical stiffness. Since NHE1 overexpression stimulates MMP3 secretion but does not change transmigration through a fixed substrate, MV3 cell invasion of a native substrate depends on MMP activity rather than on a modifiable cortical stiffness.


In vitro 3D culture lung model from expanded primary cystic fibrosis human airway cells.
In vitro cystic fibrosis (CF) models are crucial for understanding the mechanisms and consequences of the disease. They are also the gold standard for pre-clinical efficacy studies of current and novel CF drugs. However, few studies have investigated expansion and differentiation of primary CF human bronchial epithelial (CF-HBE) cells. Here we describe culture conditions to expand primary CF airway cells while preserving their ability to differentiate into 3D epithelial cultures expressing functional cystic fibrosis transmembrane conductance regulator (CFTR) ion channels that responds to CFTR modulators. Primary CF airway cells were expanded using PneumaCultTM-Ex Plus (StemCell Technologies) medium with no feeder cells or added Rho kinase (ROCK) inhibitor. Differentially passaged CF-HBE cells at the air-liquid interface (ALI) were characterized phenotypically and functionally in response to the CFTR corrector drug VX-661 (Tezacaftor). CF-HBE primary cells, expanded up to six passages (~25 population doublings), differentiated into 3D epithelial cultures as evidenced by trans-epithelial electrical resistance (TEER) of >400 Ohms∙cm2 and presence of pseudostratified columnar ciliated epithelium with goblet cells. However, up to passage five cells from most donors showed increased CFTR-mediated short-circuit currents when treated with the corrector drug, VX-661. Ciliary beat frequency (CBF) also increased with the corrector VX-661. CF donor-derived airway cells can be expanded without the use of feeder cells or additional ROCK inhibitor, and still achieve optimal 3D epithelial cultures that respond to CFTR modulators. The study of rare CF mutations could benefit from cell expansion and could lead to the design of personalized medicine/treatments.


A qualitative exploration of Malaysian cancer patients' perceptions of cancer screening.
Despite the existence of different screening methods, the response to cancer screening is poor among Malaysians. The current study aims to examine cancer patients' perceptions of cancer screening and early diagnosis. A qualitative methodology was used to collect in-depth information from cancer patients. After obtaining institutional ethical approval, patients with different types and stages of cancer from the three major ethnic groups (Malay, Chinese and Indian) were approached. Twenty semi-structured interviews were conducted. All interviews were audiotaped, transcribed verbatim, and translated into English for thematic content analysis. Thematic content analysis yielded four major themes: awareness of cancer screening, perceived benefits of cancer screening, perceived barriers to cancer screening, and cues to action. The majority of respondents had never heard of cancer screening before their diagnosis. Some participants reported hearing about mammogram and Pap smear tests but did not undergo screening due to a lack of belief in personal susceptibility. Those who had negative results from screening prior to diagnosis perceived such tests as untrustworthy. Lack of knowledge and financial constraints were reported as barriers to cancer screening. Finally, numerous suggestions were given to improve screening behaviour among healthy individuals, including the role of mass media in disseminating the message 'prevention is better than cure'. Patients' narratives revealed some significant issues that were in line with the Health Belief Model which could explain negative health behaviour. The description of the personal experiences of people with cancer could provide many cues to action for those who have never encountered this potentially deadly disease, if incorporated into health promotion activities.


The effects of rotator cuff tears, including shoulders without pain, on activities of daily living in the general population.
Few reports have so far evaluated the possible restrictions of activities of daily living (ADL) in patients with asymptomatic rotator cuff tears (RCTs). The purpose of this study was to examine the effects of RCTs, including shoulders without pain, on ADL in the general population. We performed medical checkups on 462 individuals (924 shoulders). All participants completed a questionnaire regarding their background and medical history. We then assessed their shoulder functions with the Simple Shoulder Test (SST) and performed US (US) examinations of both shoulders to diagnose RCTs. We divided participants into tear and nontear groups and performed statistical analysis to compare total SST scores and each SST item between groups. Furthermore, we performed the same examinations for participants identified as having shoulders without pain. Among participants, those in the tear group showed significantly lower total SST scores than those in the nontear group. After examining each SST item, a significant difference was observed regarding the ability to sleep comfortably and to lift 3.6 kg to shoulder level. In shoulders without pain, the tear group showed significantly lower total SST scores than the nontear group. A significant difference was observed only regarding the ability to lift 3.6 kg to shoulder level. In the general population, ADL were restricted in participants with RCTs; they experienced night pain in the shoulder and muscle weakness during shoulder elevation. Furthermore, participants with RCTs, even if the condition itself did not induce any pain, tended to experience muscle weakness during shoulder elevation, thus resulting in restrictions of ADL.


The impact of a high-dependency unit on the workload of an intensive care unit.
While there has been recent support for high-dependency unit development, there are few data reporting the impact of such development on existing critical care facilities. Therefore the aim of this study was to examine the workload and capacity constraints of an adult general intensive care unit before and after the development of an adjacent high-dependency unit. Following the opening of the high-dependency unit, the total number of patients admitted increased by 49%. On the high-dependency unit, more elderly patients were admitted for longer and more frequently following midweek elective surgery. On the intensive care unit, patients' initial severity of illness was lower and their duration of admission decreased; fewer patients were admitted directly from the general wards. The financial benefits of high dependency care may be eroded by the increased use of the critical care services.


Effect of levamisole on cell-mediated immune responses in patients with nasopharyngeal carcinoma.
CMI functions, as monitored by responses in the Mantoux and PHA tests, can be augmented by a short oral course of levamisole. The augmentation is dosage dependent and, in some patients, of long duration.


Implementation of 350-2500 nm diffuse reflectance spectroscopy and High-Performance Thin-Layer Chromatography to rapidly assess manufacturing consistency and quality of cotrimoxazole tablets in Tanzania.
To assess the quality of cotrimoxazole tablets produced by a Tanzanian manufacturer by a newly instituted quality assurance programme. Tablets underwent a diffuse reflectance spectroscopy procedure with periodic quality assessment confirmation by assay and dissolution testing using validated HPTLC techniques (including weight variation and disintegration evaluations). Based on results from the primary test methods, the first group of product was <80% compliant, whereas subsequent groups reached >99% compliance. This approach provides a model for rapidly assuring product quality of future procurements of other products that is more cost-effective than traditional pharmaceutical testing techniques.


Phthalate esters in the Largest River of Asia: An exploration as indicators of microplastics.
Phthalate esters (PAEs) are the most ubiquitous and highly used plasticizers in plastic products globally, yet studies on the spatial variation, risks, and their correlation with microplastics (MPs) are limited, particularly throughout the Yangtze River (the largest river in China/Asia). Therefore, this study investigated for the first time the PAEs pollution characteristics throughout the Yangtze River sediments, studied the environmental factors linked to the distribution of PAEs, and explored their potential as chemical indicators for interpreting pollution patterns of MPs. Totally 14 out of 16 PAEs were detected in sediments, with total concentrations ranging from 84.67 ng/g to 274.0 ng/g (mean: 163.5 ng/g), dominated by Bis(2-ethylhexyl) phthalate (DEHP), Di-n-butyl phthalate (DBP), and Di-isobutyl phthalate (DIBP), with contributions of 38.9 %, 31.8 %, and 20.8 %, respectively. Spatial distribution of PAEs did not indicate significant differences, which may be related to anthropogenic activities (i.e., emission intensity), runoff, and sediment physicochemical properties (i.e., TOC and TN), with TOC and TN being potential predictors of PAEs. The quantitative relationships (p < 0.001) between DEHP/∑16PAEs ratio and MPs (both individual and total MPs) were found in sediments, which suggested that DEHP could be potentially used as an indicator for MPs. DEHP, DIBP, and DBP posed high risks, accounting for 100 %, 68.4 %, and 10.5 % of the monitoring sites, respectively. Further work is necessary to better understand the relationship between DEHP/∑16PAEs and MPs in the environment and to take corresponding management and control measures for these pollutants.


Separase, polo kinase, the kinetochore protein Slk19, and Spo12 function in a network that controls Cdc14 localization during early anaphase.
In budding yeast, the phosphatase Cdc14, a key regulator of exit from mitosis, is released from its inhibitor Cfi1/Net1 in the nucleolus during anaphase. A signaling cascade, known as the mitotic exit network (MEN), controls this release. We have identified a regulatory network, the FEAR (Cdc fourteen early anaphase release) network that promotes Cdc14 release from the nucleolus during early anaphase. The FEAR network is comprised of the polo kinase Cdc5, the separase Esp1, the kinetochore-associated protein Slk19, and Spo12. We also show that the FEAR network initiates Cdc14 release from Cfi1/Net1 during early anaphase, and MEN maintains Cdc14 in the released state during late anaphase. We propose that one function of Cdc14 released by the FEAR network is to stimulate MEN activity.


Clinical predictors of nephrotoxicity associated with teicoplanin: Meta-analysis and meta-regression.
Teicoplanin is a glycopeptide antibiotic against methicillin-resistant Staphylococcus aureus infections. However, the impact of clinical characteristics on nephrotoxicity associated with teicoplanin has not been determined. This meta-analysis aimed to investigate the relationship between clinical characteristics and nephrotoxicity associated with teicoplanin. We identified clinical research published from January 1975 to June 2021 using PubMed, Cochrane Library, and Scopus, which described the nephrotoxicity associated with teicoplanin. Meta-analysis determined the incidence of nephrotoxicity. Using meta-regression analysis, we evaluated the impact of clinical characteristics on outcomes. Of the 567 articles, eight articles including 634 patients were analysed. The overall incidence of nephrotoxicity associated with teicoplanin was 11.0% (95% confidence interval: 8.0-13.0) for the fixed-effect model. Additionally, patients with >65 years had a high trend for the risk of nephrotoxicity compared to those with ≤65 years (>65 years; 12.0% [95% confidence interval: 9.0-15.0] vs. ≤65 years; 7.0% [95% confidence interval: 3.0-12.0], p = 0.09) for the fixed-effect model. Meta-regression analysis demonstrated that only serum albumin level negatively correlated with the risk of nephrotoxicity (y = -17.0 x + 56.7, r = 0.74, p = 0.01). This meta-analysis ascertained that hypoalbuminemia leads to nephrotoxicity associated with teicoplanin.


Can Doctors Maintain Good Character? An Examination of Physician Lives.
Can doctors maintain good character? This paper shifts the focus from patient care to ethical considerations that bear on the physician and impact her as a person. By decentering patient care, the paper highlights certain factors that habituate a particular way of reasoning that is not conducive to inculcating good character. Such factors include, standards of professionalism, being influenced by external monitors, and emphasis on adherence to guidelines. While such factors may benefit patients, they often adversely affect the character of physicians.


A red metallic oxide photocatalyst.
Light absorption across the bandgap in semiconductors is exploited in many important applications such as photovoltaics, light emitting diodes and photocatalytic conversion. Metals differ from semiconductors in that there is no energy gap separating occupied and unoccupied levels; however, it is still possible to excite electrons between bands. This is evidenced by materials with metallic properties that are also strongly coloured. An important question is whether such coloured metals could be used in light harvesting or similar applications. The high conductivity of a metal would preclude sufficient electric field being available to separate photocarriers; however, the high carrier mobility in a metal might also facilitate kinetic charge separation. Here we clearly demonstrate for the first time the use of a red metallic oxide, Sr(1-x)NbO(3) as an effective photocatalyst. The material has been used under visible light to photocatalyse the oxidation of methylene blue and both the oxidation and reduction of water assisted by appropriate sacrificial elements.


Haemophilus influenzae meningitis: a 5-year study in Ibadan, Nigeria.
A total of 131 children with Haemophilus influenzae meningitis was studied over a period of 5 years. Of these, 92% and of those who died from this disease, 94% were 2 years old or less. Mortality was 26% and morbidity among the survivors was 36%. Most of the children studied were marasmic. The seasonal incidence is discussed since incidence peaked mainly in the dry season with a secondary peak in the rainy season. Haemoglobin (H6) electrophoresis, done in respect of a few children, showed a significantly higher incidence of Hb SS among patients than in the general population. This relationship is being studied further. The prognosis did not appear to be significantly affected by the choice between a combination of penicillin and chloramphenicol on the one hand and ampicillin alone on the other. A combination of penicillin and chloramphenicol is preferred to chloramphenicol alone in initiating therapy because 100% of strains of H. influenzae isolated in our laboratory are susceptible to chloramphenicol but only 75% of strains of Streptococcus pneumoniae are susceptible to this drug.


Reliability of lumbar spinal palpation, range of motion, and determination of position.
The study purposes were to investigate the level of agreement of palpation of lumbar spinous processes between examiners, test-retest repeatability of lumbar spine range of motion, and the reliability of upright position measures in asymptomatic subjects. The modified CA 6000 spinal motion apparatus with a new skin fixation system was used by three operators for the test-retest spine measurements (3 days apart), and to obtain measures at one session of spinal position. Mean ranges of motion in all planes for 22 asymptomatic subjects were reported using the Intra-class Correlation Coefficient. Overall, differences in palpation agreement for lumbar segments occurred in three subjects and did not affect range of motion values. For upright spinal position, ICC (2,3) values for sagittal, coronal, and horizontal plane positions were 0.96, 0.80, and 0.98 respectively. There were statistically significant differences between examiners for position values, determined by the Bonferroni t-test (p < 0.05), but the magnitude of the differences were 2 degrees or less, and not considered clinically important. Results suggest that lumbar spinal motion measurements and position determination between different operators can be consistent particularly if utilizing the modified instrument. Static lumbar position also appears to be recorded reliably between different operators. Results justify progression to multi-center lumbar research using the modified CA 6000 and the work is considered relevant to medical clinicians working with spinal dysfunction, surgical interventions, or occupational health.


Optical detection of phase transitions in simple and mixed lipid-water phases.
A simple method for the detection of phase transitions in lipid-water systems by recording the intensity of the transmitted light through a sample placed between crossed polarizers as a function of the temperature was developed. A very small amount of lipid material is sufficient for its effective application. Two zwitterionic lipids in water, dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine (DPPE) as well as their mixtures were studied by means of this method. The results were compared with differential scanning calorimetry (DSC) data and a good correspondence was established. A phase diagram of the DPPC-DPPE mixture is constructed. This study also throws additional light on the nature of the 'pretransition' of DPPC.