Immune mechanisms and molecular mediators of glomerular injury in experimental nephritis. Summary of current results and continuing studies.
Despite a growing body of evidence on the importance of macrophage accumulation in renal glomeruli to the subsequent injury in experimental immune nephritis, exact mechanisms of the monocyte/macrophage recruitment and phenomena leading to tissue damage are not completely clarified. Our experiments indicate that neutral proteinases released in situ by activated macrophages may, at least in part, be responsible for the development of autoimmune nephrotoxic glomerulonephritis in rats. Accordingly, apart from the well-established features of glomerular hypercellularity and basement membrane damage, a new mechanism of direct cytolysis by macrophage-derived proteinases is postulated to be of potential relevance to the nephritic glomerular injury.


A retrospective analysis of costs and patterns of treatment for external genital warts in The Netherlands.
External genital warts (EGWs) are one of the most common sexually transmitted infections, but little is known about the treatment patterns or resources used in the management of this condition. The purpose of this retrospective analysis is to examine the patterns of treatment, resource utilization, and costs for EGWs in 3 dermatology clinics in the Netherlands. A total of 530 completed episodes of care for EGWs were analyzed to identify patterns of treatment and resources used. Costs of care were calculated based on 4 cost components for each visit: labor costs, material costs, indirect costs, and extra costs. Across the 3 sites, men required an average of 5.78 clinic visits to achieve a completed episode of care; women required an average of 6.52 visits. The distribution of visits is highly skewed, however, with a median of 4.56 visits for men and 5.55 for women. More than 80% of patients were initially treated with monotherapy. Podophyllin and cryotherapy were the principal choices for initial therapy. The mean cost, in euros, of completing an episode of care was 221.34 euro for men and 292.29 euro for women. The cost per completed or successful episode of care was 395.92 euro for men and 485.05 euro for women. The distribution of costs was also skewed, with a relatively small group of patients accounting for a considerable proportion of overall costs. Although only 31.4% of male patients recorded > or = 6 visits for a completed episode of care, this group accounted for 57.3% of the total costs of treatment for male patients. Among female patients, 43.4% had > or = 6 visits, which accounted for 73.9% of the total costs of care for female patients. Costs also varied markedly by therapy sequence chosen. Patients who remained on their initial monotherapy or combination therapy had the lowest costs; the extent to which patients switched therapies substantially affected overall costs. For those patients initially treated with podophyllin, the mean total costs of treatment, taking into account the proportion who required a change in therapy, were 204.84 euro for men and 386.38 euro for women. For those initially treated with cryotherapy, the mean cost of treatment was 193.60 euro for men and 169.23 euro for women. Current treatment options for EGWs do not appear to minimize resource utilization or help achieve complete episodes of care at the lowest possile cost.


Glucose-dependent enhancement of spontaneous phasic contraction is suppressed in diabetic mouse portal vein: association with diacylglycerol-protein kinase C pathway.
We investigated portal vein (PV) contractility in diabetes using a mouse model (ob/ob mouse) of spontaneous noninsulin-dependent diabetic mellitus. Spontaneous phasic contraction in control mice (C57Bl) was increased in the presence of the thromboxane A(2) analog 9,11-dideoxy-11alpha, 9alpha-epoxymethanoprostaglandin F(2)alpha (U46619) in a time- and concentration-dependent manner. This response was enhanced under high glucose conditions (22.2 mM). Diacylglycerol (DG) was synthesized from glucose and was not affected by phospholipase C (PLC) inhibition under resting conditions in normal glucose. Inhibition of DG-induced PKC activation with 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo-(2,3-alpha)pyrrolo(3,4-c)-carbazole (Gö6976), a calcium-dependent protein kinase C (PKC) inhibitor, was only observed under normal glucose conditions. High glucose levels enhanced PLC-independent DG formation followed by an induction of total phosphatidylinositol turnover via calcium-independent PKC activation in C57Bl mice. In ob/ob mice, the high glucose-induced enhancement of PV contraction in response to U46619 was suppressed. These findings suggest that these differences are associated with long-term exposure of tissue to a hyperglycemic state. Under high glucose conditions, DG derived from glucose fell below 50% in C57Bl mice. Moreover, the DG-related calcium-independent PKC was desensitized in ob/ob mice. These results suggest that suppression of the glucose-induced enhancement of PV contraction involves both a decrease in glucose-derived DG formation and reduction of the glucose sensitivity of DG-related PKC.


Increased Lower Limb Spasticity but Not Strength or Function Following a Single-Dose Serotonin Reuptake Inhibitor in Chronic Stroke.
To investigate the effects of single doses of a selective serotonin reuptake inhibitor (SSRI) on lower limb voluntary and reflex function in individuals with chronic stroke. Double-blind, randomized, placebo-controlled crossover trial. Outpatient research setting. Individuals (N=10; 7 men; mean age ± SD, 57±10y) with poststroke hemiplegia of >1 year duration who completed all assessments. Patients were assessed before and 5 hours after single-dose, overencapsulated 10-mg doses of escitalopram (SSRI) or placebo, with 1 week between conditions. Primary assessments included maximal ankle and knee isometric strength, and velocity-dependent (30°/s-120°/s) plantarflexor stretch reflexes under passive conditions, and separately during and after 3 superimposed maximal volitional drive to simulate conditions of increased serotonin release. Secondary measures included clinical measures of lower limb coordination and locomotion. SSRI administration significantly increased stretch reflex torques at higher stretch velocities (eg, 90°/s; P=.03), with reflexes at lower velocities enhanced by superimposed voluntary drive (P=.02). No significant improvements were seen in volitional peak torques or in clinical measures of lower limb function (lowest P=.10). Increases in spasticity but not strength or lower limb function were observed with single-dose SSRI administration in individuals with chronic stroke. Further studies should evaluate whether repeated dosing of SSRIs, or as combined with specific interventions, is required to elicit significant benefit of these agents on lower limb function poststroke.


NQF seeks measures for reporting of infections.
Proposed measures had to be fully developed for use (e.g., research and testing have been completed) and be applicable to health care-associated infections. Initiative guided by NQF mission to help standardize the way quality of performance is measured and reported. Main objective is to establish "best in class" standards that hospitals can use in benchmarking.


Diagnostic value of maspin in distinguishing adenocarcinoma from benign biliary epithelium on endoscopic bile duct biopsy.
Histopathologic distinction between benign and malignant epithelia on endoscopic bile duct biopsy can be extremely challenging due to small sample size, crush artifact, and a propensity for marked inflammatory and reactive changes after stent placement. Our previous studies have shown that the insulin-like growth factor II mRNA-binding protein 3, S100P, and the von Hippel-Lindau gene product (pVHL) can help the distinction. This study analyzed 134 endoscopic bile duct biopsy specimens (adenocarcinoma 45, atypical 31, and benign 58) by immunohistochemistry for the expression of maspin, a serine protease inhibitor. The results demonstrated that (1) maspin expression was more frequently detected in malignant than in benign biopsies; (2) malignant biopsies frequently showed diffuse, strong/intermediate, and combined nuclear/cytoplasmic staining patterns for maspin, which were much less commonly seen in benign biopsies; (3) the malignant staining patterns for maspin observed in atypical biopsies were consistent with follow-up data showing that 67% of these patients were subsequently diagnosed with adenocarcinoma; (4) a maspin+/S100P+/pVHL- staining profile was seen in 75% of malignant biopsies but in none of the benign cases. These observations demonstrate that maspin is a useful addition to the diagnostic immunohistochemical panel (S100P, pVHL, and insulin-like growth factor II mRNA-binding protein 3) to help distinguish malignant from benign epithelia on challenging bile duct biopsies.


A structural basis for the aortic stress-strain relation in uniaxial tension.
A constitutive law that includes three analytical expressions was recently proposed to approximate the low, physiologic, and high-stress parts of the aortic stress-strain relation in uniaxial tension, consistent with the biphasic nature of the aortic wall under passive conditions. This consistency, and the fact that previous phenomenological uniaxial laws have only indirectly been related to vessel wall structure, motivates the investigation of the structural basis underlying the newly proposed three-part constitutive law. For this purpose, longitudinally oriented aortic strips were fixed in Karnovsky's solution, while subjected to various pre-selected levels of uniaxial tensile stress. Light microscopy examination disclosed that the elastic lamellae gradually unfolded at low and were almost straight at physiologic and high stresses, while collagen fibers reoriented in the longitudinal axis at low, started uncoiling at physiologic, and straightened massively at high stresses. In the circumferential sections, the elastic lamellae and the circumferentially distributed collagen bundles remained wavy at all levels of longitudinally applied stress. These microstructural changes suggest that elastin becomes load-bearing at low, and collagen at physiologic but mostly at high stresses, so that the first and third parts of the constitutive law are in turn due to the presence of elastin and collagen alone, and the second due to both elastin and collagen. The structural basis of this constitutive law allows physically significant interpretation of its parameters, offering insight into how the aortic microstructure determines the macromechanical response.


Cyclophosphamide, vinblastine, procarbazine and prednisone with CCNU and vinblastine maintenance for advanced Hodgkin's disease.
Fifty patients with advanced Hodgkin's disease were treated with a combination of cyclophosphamide, vinblastine, procarbazine and prednisone (CVPP) in a 21-day cyclic regimen. Thirty-one patients (62%) achieved a pathologically documented complete remission (CR). Of the 23 previously untreated patients, 13 obtained CR. Twenty-seven patients had been previously treated and 15/19 (79%) of those with prior major radiation therapy and 3/8 (37.5%) of those who had received both irradiation and chemotherapy achieved CR. Sixteen of the patients who attained CR received maintenance therapy with monthly alternating CCNU and vinblastine but as of this report, neither remission duration nor survival is significantly prolonged when compared to the 14 patients followed in remission on no therapy. Patients who received more than six courses of induction therapy (median 9.5, range 8-12) have had significantly fewer relapses and longer remissions than have those patients who received only six courses of therapy. It is concluded that: 1) CVPP is an effective regimen at inducing CR in patients with advanced Hodgkin's disease and has less gastrointestinal and neurologic toxicity than MOPP; 2) maintenance therapy with CCNU and vinblastine to date has not been beneficial; and 3) greater than six courses of induction chemotherapy prolongs remission duration and is associated with fewer disease relapses.


Practice improves adults' sensitivity to diagonals.
Adults who were initially less sensitive to a diagonal, 10 c/deg sinusoidal grating, practiced detecting it for 3000 yes-no signal detection trials. Following practice all observers had improved their relative sensitivity to the diagonal and most were as sensitive to the diagonal as to cardinal (horizontal or vertical) orientations. Practicing a cardinal axis, on the other hand, caused no improvement in sensitivity unless the pre-practice threshold for that orientation was elevated with respect to other orientations. Three hypotheses are proposed to account for the improved sensitivity. The results are also related to the typical pattern of adult anisotropic contrast sensitivity which favors the cardinal orientations.


Pediatric and Geriatric-Friendly Buccal Foams: Enhancing Omeprazole Delivery for Patients Encountering Swallowing Difficulties.
Buccal foams containing omeprazole (OME) have been developed as potential drug delivery systems for individuals encountering swallowing difficulties, particularly pediatric and geriatric patients. The buccal foams were formulated from lyophilized aqueous gels of maltodextrin, used as a sweetener, combined with various polymers (alginate, chitosan, gelatin, tragacanth) to fine tune their structural, mechanical, and physicochemical properties. Consistent with the requirements for efficient drug delivery across buccal epithelium, the foam comprised of hydroxypropyl methylcellulose and alginate (HPMC-Alg-OME), exhibited moderate hardness and high mucoadhesion resulting to prolonged residence and increased transport of the active across porcine epithelium. The HPMC-Alg-OME foam induced a 30-fold increase in the drug's apparent permeability across porcine buccal tissue, compared to the drug suspension. The developed buccal foams exhibited excellent stability, as evidenced by the unchanged omeprazole content even after six months of storage under ambient conditions (20 °C and 45% RH). Results indicate that buccal foams of omeprazole may address the stability and ease of administration issues related to oral administration of the drug, particularly for children and elderly patients who have difficulty swallowing solid dosage forms.


Government environmental control measures on CO2 emission during the 2014 Youth Olympic Games in Nanjing: Perspectives from a top-down approach.
Strict air pollution control measures were conducted during the Youth Olympic Games (YOG) period at Nanjing city and surrounding areas in August 2014. This event provides a unique chance to evaluate the effect of government control measures on regional atmospheric pollution and greenhouse gas emissions. Many previous studies have observed significant reductions of atmospheric pollution species and improvement in air quality, while no study has quantified its synergism on anthropogenic CO2 emissions, which can be co-reduced with air pollutants. To better understand to what extent these pollution control measures have reduced anthropogenic CO2 emissions, we conducted atmospheric CO2 measurements at the suburban site in Nanjing city from 1st July to 30th September 2014 and 1st August to 31st August 2015, obvious decrease in atmospheric CO2 was observed between YOG and the rest period. By coupling the a priori emission inventory with atmospheric transport model, we applied the scale factor Bayesian inversion approach to derive the posteriori CO2 emissions in YOG period and regular period. Results indicate CO2 emissions from power industry decreased by 45%, and other categories also decreased by 16% for manufacturing combusting, and 37% for non-metallic mineral production. Monthly total anthropogenic CO2 emissions were 9.8 (±3.6) × 109 kg/month CO2 for regular period and decreased to 6.2 (±1.9) × 109 kg/month during the YOG period in Nanjing city, with a 36.7% reduction. When scaling up to whole Jiangsu Province, anthropogenic CO2 emissions were 7.1 (±2.4) × 1010 kg/month CO2 for regular period and decreased to 4.4 (±1.2) × 1010 kg/month CO2 during the YOG period, yielding a 38.0% reduction.


Unsupervised aided investigation on the associations between municipal solid waste characteristics and socio-economic conditions.
Better municipal solid waste (MSW) management can help to address environmental concerns and supports economic and social development. Because MSW characteristics can change over time, management strategies should also evolve and be applied correspondingly. However, many previous studies have focused on MSW characterization or investigated specific management strategies for a target MSW. Few studies have assessed the spatial variations of MSW characteristics and socio-economic (SE) conditions as well as their associations. This study evaluated the feasibility of using an integrated unsupervised method (cluster analysis and cross-tabulation analysis) to explore these topics for MSW management. Results suggest that the integrated method can successfully help to reveal key information. Seven jointed MSW-SE scenarios were investigated based on 259 individual observations of Taiwan. Associations between MSW compositions and SE conditions were identified statistically significant for four MSW-SE scenarios. In general, the general SE type (SE1) is very likely to generate high food wastes and other combustible, low paper, wood, and rubber wastes (MSW1). The small island SE type (SE3) is more likely to produce high paper and low wood, rubber, textile, and other noncombustible wastes (MSW2). Overall, the method applied in this study could help to reveal statistical associations between MSW and SE, which can help decision-makers comprehend underlying facts and develop effective management strategies.


Evaluation of the relationship between GPR43 and adiposity in human.
GPR43 is a G-protein-coupled receptor that participates in adipocyte differentiation in mice and is over-expressed in adipose tissue of obese mice. The aim of this study was to investigate the implication of GPR43 in adipogenesis in humans and to determine the influence of obesity on its expression in human adipose tissue. Preadipocytes were isolated from human omental adipose tissue and cultured during 13 days. One PPARγ agonist (troglitazone) and three GPR43 agonists (two physiological and one synthetic) were tested for their ability to induce differentiation. After 13 days, the three GPR43 agonists had no impact on aP2 expression, a marker of adipocyte differentiation, whereas troglitazone led to a huge over-expression of aP2 in these cells but tended to decrease GPR43 expression (p=0.06).GPR43 and inflammatory markers expression was also quantified in omental adipose tissue from lean and obese individuals. GPR43 expression in total adipose tissue was similar between obese patients and lean subjects and did not correlate with aP2 expression. In contrast, GPR43 expression positively correlated with TNFα mRNA. Our results suggest the absence of relationship between GPR43 and adipocyte differentiation in humans, unlike what was observed in mice. Furthermore, GPR43 expression is not increased in adipose tissue from obese subjects but could be related to TNFα-related inflammatory processes.


Analog and digital computer theory.
Analog signals abound in the natural world. With appropriate transducers these signals can be converted to continuous voltages and can be displayed, transmitted, stored, or copied. They can be processed by analog computers, the simplest of which is an audio amplifier. With analog signals, however, there can be errors because of signals loss, interference, and noise. Binary digital signals permit only two values, either 0 ('off' or 'low') or 1 ('on' or 'high'). These signals are much less susceptible to transmission problems. Binary signals are commonly organized into 8-bit groups which can represent 256 different numbers or meanings. These data can be transmitted in either serial or parallel fashion at high rates of speed. Analog-to-digital converters permit analog signals to be transformed to digital signals. A computer consists of the memory, the processor, and the input/output devices. Memory includes the fastest registers, the very fast core memory, the peripheral storage devices such as diskettes and disks, and the very slow peripheral devices such as magnetic tape. The processor can only load and store numbers in memory, add two numbers, test a number, and provide input and output. The program counter indicates the next computer instruction to be performed. Input/output devices allow communication with the outside world and may assume many forms. A computer by itself can do nothing. A program or series of instructions is required. The most simplistic program language is assembler or machine language. Most programming is done in more sophisticated languages, however.(ABSTRACT TRUNCATED AT 250 WORDS)


The (YXXL/I)2 signalling motif found in the cytoplasmic segments of the bovine leukaemia virus envelope protein and Epstein-Barr virus latent membrane protein 2A can elicit early and late lymphocyte activation events.
The cytoplasmic domains of the transducing subunits associated with B and T cell antigen receptors contain a common amino acid motif consisting of two precisely spaced Tyr-X-X-Leu/Ile sequences (where X corresponds to a variable residue). Expression of a single copy of this motif suffices to initiate B or T cell activation. The bovine leukaemia virus (BLV) is a B cell lymphotropic retrovirus which causes a non-neoplasic proliferation of B cells. The cytoplasmic domain of the BLV transmembrane envelope glycoprotein, gp30, possesses two overlapping copies of the Tyr-X-X-Leu/Ile-containing motif which could participate in the induction of B cell activation. Similarly, the N-terminal cytoplasmic domain of the latent membrane protein 2A (LMP2A) of the Epstein-Barr virus (EBV) contains a single copy of the Tyr-X-X-Leu/Ile-containing motif which could play a critical role in B cell transformation. To determine whether these two virus-encoded cytoplasmic domains are endowed with signalling functions, we constructed chimeric proteins by replacing the cytoplasmic tail of CD8-alpha with that of either BLV gp30 or EBV LMP2A. We show here that, once separately expressed in B or T cell lines, these chimeras are capable of triggering both calcium responses and cytokine production when cross-linked with an antibody to CD8-alpha. Furthermore, using site-directed mutagenesis, we demonstrated unequivocally that this signalling function may be accounted for by the Tyr-X-X-Leu/Ile motifs they contain.(ABSTRACT TRUNCATED AT 250 WORDS)


RT-qPCR with chimeric dU stem-loop primer is efficient for the detection of bacterial small RNAs.
Small non-coding RNAs are considered be involved in the regulation of multiple cellular processes. Quantitative reverse transcription PCR (RT-qPCR) is widely used in the detection of eukaryotic microRNA, and the stem-loop primers can improve the specificity and efficiency of reverse transcription. However, the loop structure of primers probably influence the next quantitative amplification due to the base stacking and steric hindrance. Here, we designed a chimeric stem-loop primer with a deoxyuracil (dU) base located near the RNA matching part. After the reverse transcription, uracil-DNA glycosylase (UDG) treatment was used to remove the dU base and destroy the stem-loop structure of RT product. Enzymatic assay confirmed that the recombinant UDG could efficiently eliminate the dU base in the oligonucleotide. Transcriptions of two small RNAs (TFF and ryeA) in Escherichia coli were detected by RT-qPCR with different primers. Results showed that the use of the chimeric dU stem-loop primer and UDG treatment could enhance the detection specificity and sensitivity about 1.1- to 3.4-fold, compared to those with traditional stem-loop primer and linear primer. Total RNA of 1-10 pg was enough for efficient detection with the chimeric stem-loop primers. In a word, this strategy could promote the RT-qPCR detection efficiency on the transcription of bacterial small RNAs even in trace samples and can facilitate the detection of exiguous change in cellular metabolism.


Comparison of metabolic effects of surgical-induced massive weight loss in patients with long-term remission versus non-remission of type 2 diabetes.
The aim of this study was to evaluate the pathophysiological mechanisms underlying the non-remission of type 2 diabetes in Roux-en-Y gastric bypass (RYGB) patients. A group of patients not in remission (NR) was formed (n = 13). A remission group (R) was composed of patients who had undergone normalization of fasting glycemia and A1c, without anti-diabetic drugs and matched for selected baseline characteristics (i.e., duration of disease, previous BMI, final BMI, fat distribution, and age; n = 15). A control group of lean subjects (n = 41) was formed. The NR group had higher uric acid (5.1 vs. 3.9 mg/dL), number of leukocytes (6,866.9 vs. 5,423.6), hs-CRP (0.27 vs. 0.12 mg/dL), MCP-1 (118.4 vs. 64.4 ng/mL), HOMA-IR, and AUC(glucose) but lower adiponectin (9.4 vs. 15.4 ng/mL), leptin (12.7 vs. 20.7 ng/mL), and AUC(GLP-1) in comparison to R group; the NR group also had lower leptin and higher adiponectin, HOMA-IR, AUC(glucose), AUC(C-peptide), AUC(glucagon), and AUC(GLP-1) than controls. The R group had lower MCP-1 and higher adiponectin compared to controls. Insulin sensitivity was significantly lower in the NR group than in the R and control groups. The insulin secretion index values were lower in the NR group than in the R and control groups. This study found greater insulin resistance, lower insulin secretion, persistent adiposopathy and chronic subclinical inflammation, and less robust incretin response in the NR group despite a similar level of weight loss. Persistently altered pathophysiological mechanisms can be related to the lack of remission of type 2 diabetes after RYGB.


Testing for variants in CYP2C19: population frequencies and testing experience in a clinical laboratory.
We sought to determine the genotype frequencies for cytochrome p450 enzyme 2C19 variant alleles both in the US pan-ethnic population and various US ethnic groups and to establish the frequency of clinically actionable genotypes. Analytical results were obtained from 1,396 consecutive samples submitted for cytochrome p450 enzyme 2C19 genotyping tests and stored in a proprietary database. This database was queried and genotypes and predicted phenotypes established. Anonymized samples were obtained from specimens submitted for cystic fibrosis genotyping that contained ethnicity information. Samples from 357, 149, and 346 individuals self-identified as white, African American, and Hispanic, respectively, were analyzed. In addition, 342 anonymized samples submitted for Ashkenazi Jewish panel testing were analyzed. Significant ethnic differences were observed in the frequencies of the *17 ultrarapid allele among the various groups studied. In the pan-ethnic population, 3.8% of tested patients were classified as ultrarapid metabolizers, 24% as extensive metabolizers heterozygous for a *17 ultrarapid allele, 27% as intermediate metabolizers, and 3.5% as poor metabolizers. Using stringent criteria, 7.3% of individuals would have clinically actionable genotypes. In addition, we detected two individuals with a haplotype of *2/*17 and a single individual with a haplotype of *4/*17 indicating that the *17 hypermetabolic allele can occur on a *1, *2, or *4 background.


Glucose-6-phosphate dehydrogenase deficiency and Southeast Asian ovalocytosis in asymptomatic Plasmodium carriers in Sumba island, Indonesia.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency and Southeast Asian ovalocytosis (SAO) caused by a 27-bp deletion in the band 3 gene (Band3Delta 27) are well-documented genetic traits resistant to malarial diseases; however, relationships between these traits and asymptomatic malaria infection hitherto had not been investigated. Filter-blotted blood samples were collected from a total of 210 healthy individuals, 100 males and 110 females, aged 6-17 years, in Sumba island, Indonesia, to survey for the presence of Plasmodium parasites, G6PD activity and the Band3Delta 27 mutation. Presence of P. falciparum and/or P. vivax was identified in 25 subjects (11.9%). In all, 24 subjects (11.4%) showed Band3Delta 27 heterozygously. In males and females, eight and nine subjects, respectively, showed G6PD deficiency. There was no significant difference in the prevalence of asymptomatic malaria infection between individuals with or without these traits (P>0.05). No alterations in the prevalence of asymptomatic malaria infection suggest that parasite invasion into erythrocytes is unlikely to be a target phase in which the two polymorphisms demonstrate possible protective effects against malaria.


Energies of charge transfer and formation equilibria of the complexes of [70]fullerene with some interesting polyaromatic molecules.
We have investigated electron donor-acceptor complexes of [70]fullerene with various polyaromatic molecules (PAM) with different vertical ionization potentials (I(D)(v)). Well defined charge transfer (CT) absorption bands have been located in the visible region. We extract degrees of charge transfer, oscillator and transition dipole strengths by analyzing the transition energy of the CT band as a function of I(D)(v) of the donors studied. The experimental results were explained using a theoretical model that takes into account the interaction between electronic subsystems of PAM with [70]fullerene. Trends in the formation constant for the [70]fullerene/PAM complexes were discussed in terms of enthalpies and entropies of formation.


Neurodegenerative Disorders of Alzheimer, Parkinsonism, Amyotrophic Lateral Sclerosis and Multiple Sclerosis: An Early Diagnostic Approach for Precision Treatment.
Neurodegenerative diseases (NDs) are characterised by progressive dysfunction of synapses, neurons, glial cells and their networks. Neurodegenerative diseases can be classified according to primary clinical features (e.g., dementia, parkinsonism, or motor neuron disease), anatomic distribution of neurodegeneration (e.g., frontotemporal degenerations, extrapyramidal disorders, or spinocerebellar degenerations), or principal molecular abnormalities. The most common neurodegenerative disorders are amyloidosis, tauopathies, a-synucleinopathy, and TAR DNA-binding protein 43 (TDP-43) proteopathy. The protein abnormalities in these disorders have abnormal conformational properties along with altered cellular mechanisms, and they exhibit motor deficit, mitochondrial malfunction, dysfunctions in autophagic-lysosomal pathways, synaptic toxicity, and more emerging mechanisms such as the roles of stress granule pathways and liquid-phase transitions. Finally, for each ND, microglial cells have been reported to be implicated in neurodegeneration, in particular, because the microglial responses can shift from neuroprotective to a deleterious role. Growing experimental evidence suggests that abnormal protein conformers act as seed material for oligomerization, spreading from cell to cell through anatomically connected neuronal pathways, which may in part explain the specific anatomical patterns observed in brain autopsy sample. In this review, we mention the human pathology of select neurodegenerative disorders, focusing on how neurodegenerative disorders (i.e., Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis) represent a great healthcare problem worldwide and are becoming prevalent because of the increasing aged population. Despite many studies have focused on their etiopathology, the exact cause of these diseases is still largely unknown and until now with the only available option of symptomatic treatments. In this review, we aim to report the systematic and clinically correlated potential biomarker candidates. Although future studies are necessary for their use in early detection and progression in humans affected by NDs, the promising results obtained by several groups leads us to this idea that biomarkers could be used to design a potential therapeutic approach and preclinical clinical trials for the treatments of NDs.


The role of visible faecal material as a vehicle for generic Escherichia coli, coliform, and other enterobacteria contaminating poultry carcasses during slaughtering.
A comparison of Enterobacteriaceae, coliform and Escherichia coli counts in chicken carcasses with and without visible faecal contamination was conducted to evaluate the role of contamination as a vehicle for generic E. coli, coliform and other enterobacteria contaminating broiler chicken carcasses when processed under routine commercial operations. Samples were removed from the processing line immediately after evisceration, inside-outside shower and chilling for microbiological analysis. After evisceration, mean counts were significantly different only for E. coli (P < or = 0.05) in chicken carcasses with and without visible faecal contamination. While the spray wash practice was not efficient enough for complete removal of the visible contamination from carcasses, leading to microbiological reduction percentages lower than expected, 25 ppm chlorinated water chilling did reduce the contamination level considerably in all samples. Carcasses with and without visible faecal contamination harboured E. coli and other potentially hazardous enterobacteria. E. coli was the predominant strain isolated in all samples, Enterobacter cloacae being next most frequent. The zero tolerance of visible faecal contamination requirement alone is not sufficient to assure safety and to improve the microbial quality of carcasses.


Preoperative estimated glomerular filtration rate as a significant predictor of long-term outcomes after coronary artery bypass grafting in Japanese patients.
The aim of this retrospective study was to investigate the effect of chronic kidney disease (CKD) on outcomes after coronary artery bypass grafting (CABG), and to determine whether preoperative estimated glomerular filtration rate (eGFR) can be a predictor of long-term outcomes after CABG. 486 Japanese patients who underwent isolated CABG between December 2000 and August 2010 were evaluated. Preoperative eGFR was estimated by the Japanese equation according to guidelines from the Japanese Society of Nephrology. We defined CKD as a preoperative eGFR of less than 60 ml/min/1.73 m(2). 203 patients had CKD (CK group) and 283 patients did not (N group). During a mean observation time of 53 months, the overall survival rate was significantly lower in the CK group than in the N group (p = 0.0044). Similarly, the CK group had significantly more unfavorable results with regard to freedom from cardiac death, major adverse cardiovascular and cerebrovascular events (MACCE), and hemodialysis. Using multivariate analyses, preoperative eGFR was an independent predictor of all-cause mortality (HR 0.983; p = 0.026), cardiac mortality (HR 0.963; p = 0.006), and incidence of MACCE (HR 0.983; p = 0.002). The CK group had significantly more unfavorable outcomes than the N group. Preoperative eGFR was an independent predictor of long-term outcomes after CABG in Japanese patients.


Estimating vertically acquired HIV infections and the impact of the prevention of mother-to-child transmission program in Zimbabwe: insights from decision analysis models.
The World Health Organization recommends a single-dose nevirapine (NVP) regimen for prevention of mother-to-child transmission (PMTCT) of HIV in settings without the capacity to deliver more complex regimens, but the population-level impact of this intervention has rarely been assessed. A decision analysis model was developed, parameterized, and applied using local epidemiologic and demographic data to estimate vertical transmission of HIV and the impact of the PMTCT program in Zimbabwe up to 2005. Between 1980 and 2005, of approximately 10 million children born in Zimbabwe, a cumulative 504,000 (range: 362,000 to 665,000) were vertically infected with HIV; 59% of these infections occurred in nonurban areas. Mother-to-child transmission (MTCT) of HIV decreased from 8.2% (range: 6.0% to 10.7%) in 2000 to 6.2% (range: 4.9% to 8.9%) in 2005, predominantly attributable to declining maternal HIV prevalence rather than to the PMTCT program. Between 2002 and 2005, the single-dose NVP PMTCT program may have averted 4600 (range: 3900 to 7800) infections. In 2005, 32% (range: 26% to 44%) and 4.0% (range: 2.7% to 6.2%) of infections were attributable to breast-feeding and maternal seroconversion, respectively, and the PMTCT program reduced infant infections by 8.8% (range: 5.5% to 12.1%). Twice as many infections could have been averted had a more efficacious but logistically more complex NVP + zidovudine regimen been implemented with similar coverage (50%) and acceptance (42%). The decline in MTCT from 2000 to 2005 is attributable more to the concurrent decrease in HIV prevalence in pregnant women than to PMTCT at the current level of rollout. To improve the impact of PMTCT, program coverage and acceptance must be increased, especially in rural areas, and local infrastructure must then be strengthened so that single-dose NVP can be replaced with a more efficacious regimen.


Bidens pilosa L. exhibits high sensitivity to coumarin in comparison with three other weed species.
Nine natural plant compounds were screened for phytotoxicity to Bidens pilosa L. a troublesome weed in field and plantation crops. The sensitivity of three other weed species to coumarin, the most active identified compound, was also evaluated. Coumarin, at a concentration of 500 microM, had little effect on germination and growth of Senna obtusifolia L., Euphorbia heterophylla L., and Ipomoea grandifolia L. when compared with its effects on B. pilosa L. In a concentration range of 10-100 microM, coumarin caused a dose-dependent inhibition of germination and growth of B. pilosa L. The measurements of some parameters of energy metabolism revealed that coumarin-treated root tissues exhibited characteristics of seedlings in an earlier stage of growth, including higher respiratory activity and higher activities of alcohol dehydrogenase and lipoxygenase. These results suggest that coumarin inhibition of germination and growth of B. pilosa L. was not a consequence of an impairment of energy metabolism. Rather, it seems to act as a cytostatic agent, retarding germination. At concentrations above 50 microM, coumarin increased lipoxygenase activity and the level of conjugated dienes of root extracts, suggesting that it may induce oxidative stress in seedling roots.


Microvessel density and status of p53 protein as potential prognostic factors for adjuvant anthracycline chemotherapy in retrospective analysis of early breast cancer patients group.
A considerable subgroup of patients with early breast cancer does not address benefits of anthracycline based chemotherapy. The aim of this retrospective study was to investigate the effect of microvessel density (MVD) and status of p53 protein on 5-year disease free survival (DFS) in the group of breast cancer patients treated with anthracyclines in adjuvant setting. Correlations between MVD, p53 status and other clinicopathological parameters were also assessed. MVD and p53 status were analyzed immunohistochemically in the group of 172 women with breast cancer in clinical stage T1-2, N1-N2, M0. There were 123 tumors (71.5 %) with lower MVD (≤ 214.8 microvesells/mm(2)) and 49 (28.5 %) with higher MVD (>214.8 microvesells/mm(2)). The proportion of higher MVD tumors significantly increased in N2 (P = 0.000) and in estrogen (P = 0.046) or progesterone receptors (P = 0.029) negative tumors. p53 positivity was indicated in 50 cancers (29.1 %) and was significantly associated with higher grade (P = 0.000), steroid receptors negativity (P = 0.000), cytokeratin5/6 positivity (P = 0.026), topoisomerase IIα overexpression (P = 0.005) and higher proliferation rate (P = 0.001). In univariate analysis, higher MVD (P = 0.016) and p53 negativity (P = 0.023) were significantly related with longer DFS (median follow-up 36 months). In multivariate Cox regression analysis MVD was independently associated with DFS. These data suggest that higher MVD is favourable prognostic factors for early advanced breast cancer patients after adjuvant anthracycline based chemotherapy.


Dual-network polyacrylamide/carboxymethyl chitosan-grafted-polyaniline conductive hydrogels for wearable strain sensors.
Conductive, wearable, and flexible hydrogel-based sensors are considered as promising applications in human motion detection and physiological signal monitoring. However, it is still a problem to integrate multiple functions into one material for the next-generation smart devices. Herein, we fabricated an ionic/electronic dual conductive hydrogel by combining the chemically crosslinked polyacrylamide (PAM) and the physically crosslinked carboxymethyl chitosan-grafted-polyaniline (CMCS-g-PANI)/Ag+ network. The double-network hydrogel displays a high stretchability, repeatable adhesiveness, antibacterial activities, and biocompatibility. It also has high sensitivity and stable electrical performance for wearable strain sensors. Furthermore, we assembled a self-powered strain sensor based on the conversion of chemical energy to electrical energy. It can be used for human motion detection even without external power supply. This work provides an avenue for the development of multifunctional hydrogels with outstanding mechanical and electronic performances for application in wearable electronic devices.


Molecular dynamic simulation of mGluR5 amino terminal domain: essential dynamics analysis captures the agonist or antagonist behaviour of ligands.
We describe the application of molecular dynamics followed by principal component analysis to study the inter-domain movements of the ligand binding domain (LBD) of mGluR5 in response to the binding of selected agonists or antagonists. Our results suggest that the method is an attractive alternative to current approaches to predict the agonist-induced or antagonist-blocked LBD responses. The ratio between the eigenvalues of the first and second eigenvectors (R1,2) is also proposed as a numerical descriptor for discriminating the ligand behavior as a mGluR5 agonist or antagonist.


High serum luteinizing hormone and testosterone concentrations do not predict pregnancy outcome in women with recurrent miscarriage.
To investigate the relationship between Day 8 serum luteinizing hormone (LH) and testosterone (T) concentrations, and body mass index (BMI) with pregnancy outcome in women with recurrent miscarriage. Prospective observational study. National recurrent miscarriage clinic. Three hundred forty-four women (median age 32 years; range 18-44) with a history of recurrent first trimester miscarriage (median 4; 3-14; <12 weeks gestation) who conceived spontaneously and who received no pharmacological treatment during pregnancy were studied. All women were antiphospholipid antibody negative and had a normal peripheral karyotype as did their partners. Outcome of untreated pregnancies. Day 8 serum LH and T concentrations and BMI were correlated with pregnancy outcome. One hundred and ninety-two (55.8%) women had a live birth and 152 (44.2%) women miscarried. Polycystic ovarian morphology was diagnosed in 174 women (50.6%). There was no significant relationship between follicular phase LH concentrations and pregnancy outcome. Pregnancy outcome was similar in women with normal and high serum T concentrations. BMI value was not significantly different between women who had a live birth and those who miscarried. The analysis of this large cohort of women with recurrent miscarriage demonstrates that prepregnancy Day 8 serum LH and T concentrations, and BMI do not have a statistically significant relationship with pregnancy outcome.


Adverse effects of prenatal exposure to residential dust on post-natal brain development.
Previous studies have shown an association between prenatal exposure to particulate matter (PM) and adverse brain development. However, it is unclear whether gestational exposure to community-sampled residential PM has an impact on the developing brain. We aimed to test whether in utero exposure to PM from residential roof spaces (ceiling voids) alters critical foetal neurodevelopmental processes. Pregnant C57BL/6 mice were intranasally exposed to 100 μg of roof space particles (~5 mg kg-1) in 50 μl of saline, or saline alone under light methoxyflurane anaesthesia, throughout mid-to-late gestation. At 2 weeks post-natal age, pups were sacrificed and assessed for body and brain growth. The brain tissue was collected and examined for a range of neurodevelopmental markers for synaptogenesis, synaptic plasticity, gliogenic events and myelination by immunohistochemistry. Gestational exposure to roof space PM reduced post-natal body and brain weights. There was no significant effect of roof space PM exposure on synaptogenesis, synaptic plasticity or astrocyte density. However, PM exposure caused increased myelin load in the white matter and elevated microglial density which was dependent on the PM sample. These effects were found to be consistent between male and female mice. Our data suggest that exposure to residential roof space PM during pregnancy impairs somatic growth and causes neuropathological changes in the developing brain.


Presence of arsenic, mercury and vanadium in aquatic organisms of Laizhou Bay and their potential health risk.
This study aims at describing and interpreting concentrations of arsenic (As), mercury (Hg) and vanadium (V) in seven species of fish, three species of shellfish, one species of crab and two species of shrimp from the typical estuary-bay ecosystem. Arsenic, Hg and V differed among species, and the highest As, Hg and V were observed in shellfish. The stable nitrogen (δ15N) and carbon (δ13C) isotopes were determined to investigate the trophic interactions between fluctuating environment and aquatic species. Arsenic concentrations in samples were found negatively correlated with δ15N, implying biodilution effect of As through the food web, while Hg concentrations in samples were positively correlated with δ15N, indicating their biomagnification effect. The estimated daily intake values of Hg and V in this study were all below the oral reference dose. However, elevated As intakes of some aquatic organisms suggested a potential risk for frequent consumers.


Di-chlorido-bis-[2-(pyridin-2-yl-κN)-1H-benzimidazole-κN 3]nickel(II) monohydrate.
In the title complex, [NiCl2(C12H9N3)2]·H2O, a divalent nickel atom is coordinated by two 2-(pyridin-2-yl)-1H-benzimidazole ligands in a slightly distorted octa-hedral environment defined by four N donors of two N,N'-chelating ligands, along with two cis-oriented anionic chloride donors. The title complex crystallized with a water mol-ecule disordered over two positions. In the crystal, a combination of O-H⋯Cl, O-H.·O and N-H⋯Cl hydrogen bonds, together with C-H⋯O, C-H⋯Cl and C-H⋯π inter-actions, links the complex mol-ecules and the water mol-ecules to form a supra-molecular three-dimensional framework. The title complex is isostructural with the cobalt(II) dichloride complex reported previously [Das et al. (2011 ▸). Org. Biomol. Chem. 9, 7097-7107].


Miglitol administered before breakfast increased plasma active glucagon-like peptide-1 (GLP-1) levels after lunch in patients with type 2 diabetes treated with sitagliptin.
We recently reported that the administration of miglitol alone just before breakfast improved postprandial hyperglycemia and increased active glucagon-like peptide-1 (GLP-1) levels after lunch in men without diabetes. Miglitol and dipeptidyl peptidase-4 inhibitors, such as sitagliptin, enhance plasma active GLP-1 concentrations via different mechanisms; therefore, combined therapy with these agents was more effective than monotherapy. In this study, we compared the effectiveness of the administration of miglitol alone just before breakfast on the plasma glucose, serum insulin and glucagon, and plasma incretin levels in sitagliptin-treated patients with type 2 diabetes. We measured the plasma glucose, serum insulin and glucagon, plasma active GLP-1, and total glucose-dependent insulinotropic polypeptide levels before breakfast, at 120 min after breakfast, before lunch, and 60 and 120 min after lunch in patients with diabetes who are receiving sitagliptin. This trial was performed for the following 2 days on each subject (Day 1: no miglitol, Day 2: miglitol alone [50 mg] administered just before breakfast). The area under the curve (AUC) of the plasma glucose levels after lunch in the miglitol-treated group tended to be lower than that in the miglitol-untreated group, but the difference was not statistically significant. Miglitol alone administered at breakfast increased the AUC of the active plasma GLP-1 levels after lunch in sitagliptin-treated patients with diabetes. Our results suggest that the once-daily administration of miglitol as a "GLP-1 enhancer" in combination with sitagliptin was effective for the treatment for patients with diabetes.


Pancreatic panniculitis.
Pancreatic panniculitis is a rare disease in which necrosis of fat in the panniculus and other distant foci occurs in the setting of pancreatic disease. Our purpose was to study the clinical and histopathologic features of this disease. We conducted a retrospective review of 11 patients. In five patients subcutaneous fat necrosis preceded the diagnosis of pancreatic disease by an average of 13 weeks. Five of our patients had underlying pancreatitis, and the remainder had carcinoma of the pancreas. Joint manifestations were prominent in six patients. Intestinal submucosal fat necrosis developed in two cases and caused massive gastrointestinal bleeding in one. Acute lesions demonstrated focal fat necrosis with "ghost cells," pathognomonic of this condition. Chronic lesions showed granulomatous and lipophagic panniculitis, with rare areas of basophilic fat necrosis. Cholecystectomy for gallstone pancreatitis was curative in two patients. Pancreatic panniculitis has distinctive clinical and pathognomonic histopathologic findings that can be the presenting features of pancreatic disease.


Bimetallic co-effect of Au-Pd alloyed nanoparticles on mesoporous silica modified g-C3N4 for single and simultaneous photocatalytic oxidation of phenol and reduction of hexavalent chromium.
Perception of surface plasmonic resonance in heterogeneous photocatalysis not only has impact on basic science of sustainable energy development, but also generates green technologies for wastewater treatment, selective oxidation and reduction reactions. In the present study Au/Pd bimetallic alloyed nanoparticles were effectively decorated on mesoporous silica modified g-C3N4 (graphitic carbon nitride) nanosheets by a simple one-pot calcinations strategy. The formation of Au/Pd alloyed nanoparticles has been supported by XRD, UV-vis DRS, TEM and XPS studies. The photocatalytic performance of the photocatalysts were investigated by performing tandem reaction for simultaneous oxidation of phenol and reduction of Cr (VI). The photocatalytic performances were found to be significant for either single phenol species or single Cr (VI), but quite appreciable photocatalytic performance was observed for a solution containing Cr (VI)-phenol mixture. The synergetic effect of Au/Pd alloyed nanoparticle and enhanced photocurrent (1.4 mA/cm2) generated by the nano-composite further supports the activity. The results of tandem reaction not only reveals the feasibility of carrying out degradation of two important pollutants simultaneously from waste water, but also gives us an enlightenment to efficiently degrade mixture of pollutants without using any additional chemical as trapping agent in the photocatalytic process.


Histone H4 lysine 16 acetylation controls central carbon metabolism and diet-induced obesity in mice.
Noncommunicable diseases (NCDs) account for over 70% of deaths world-wide. Previous work has linked NCDs such as type 2 diabetes (T2D) to disruption of chromatin regulators. However, the exact molecular origins of these chronic conditions remain elusive. Here, we identify the H4 lysine 16 acetyltransferase MOF as a critical regulator of central carbon metabolism. High-throughput metabolomics unveil a systemic amino acid and carbohydrate imbalance in Mof deficient mice, manifesting in T2D predisposition. Oral glucose tolerance testing (OGTT) reveals defects in glucose assimilation and insulin secretion in these animals. Furthermore, Mof deficient mice are resistant to diet-induced fat gain due to defects in glucose uptake in adipose tissue. MOF-mediated H4K16ac deposition controls expression of the master regulator of glucose metabolism, Pparg and the entire downstream transcriptional network. Glucose uptake and lipid storage can be reconstituted in MOF-depleted adipocytes in vitro by ectopic Glut4 expression, PPARγ agonist thiazolidinedione (TZD) treatment or SIRT1 inhibition. Hence, chronic imbalance in H4K16ac promotes a destabilisation of metabolism triggering the development of a metabolic disorder, and its maintenance provides an unprecedented regulatory epigenetic mechanism controlling diet-induced obesity.


Using canopy height model derived from UAV imagery as an auxiliary for spectral data to estimate the canopy cover of mixed broadleaf forests.
Canopy cover is an important structural trait that is frequently used in forest inventories to assess sustainability as well as many other important aspects of forest stands. Remote sensing data is more effective and suitable for canopy cover estimating than traditional field measurements such as sample plots, especially at broad scales. Measurement and mapping this attribute in fine-scale is a difficult task. Aerial imagery using unmanned aerial vehicle (UAV) has been recognized as an excellent tool to estimate canopy attributes. In this study, we compared the potential of using digital hemispherical photography (DHP), digital cover photography (DCP), UAV RGB data, and canopy height model (CHM) for estimation of canopy cover of mix broad-leaved forest on seven different stands. The canopy cover was measured from two digital canopy photographic methods, including DHP (as the reference method) and DCP. The stand orthophotos were segmented using a multi-resolution image segmentation method. Afterward, the classification in two classes of the canopy cover and the non-canopy cover was conducted using minimum distance classification to estimate canopy cover. The CHM layer was generated based on the SfM algorithm and utilized in the canopy cover estimation in each stand as auxiliary data. The results showed a slight improvement when we used the CHM as auxiliary data. Overall, the results showed that the efficiency of the ground digital canopy photographic methods (zenith view) in multi-storied and dense forests is the lowest. In return, our method for digital aerial canopy photography (object-based canopy segmentation and classification) is simple, quick, efficient, and cost-effective.


Exposure to local violent crime and childhood obesity and fitness: Evidence from New York City public school students.
This paper estimates the relationship between neighborhood violent crime and child and adolescent weight and fitness. It uses detailed data from the Fitnessgram assessments of public school students in New York City matched to point specific crime data geocoded to students' residential location. Our empirical approach compares the weight and fitness outcomes of students exposed to a violent crime on their residential H-block with those living in the same census tract but not exposed to violent crime in close proximity to their home. We find for adolescent girls, increases in BMI that range from 0.01 to 0.035 standard deviations and an increase in the probability of overweight of 0.5 to 1.7 percentage points. We find little evidence that BMI, obesity, and overweight change as a result of violent crime for adolescent boys, and younger children. Results are not explained by declines in physical fitness.


Electrocardiographic findings in sickle cell cardiovascular autonomic neuropathy.
There is a lack of data on the relationship between cardiovascular autonomic neuropathy (CAN) and electrocardiographic parameters in sickle cell anaemia. The purpose of the study was to compare the electrocardiographic findings in adult sickle cell anaemia patients with CAN with those of patients without this complication. A cross sectional study was done using 62 consecutively recruited sickle cell anaemia patients who met the inclusion criteria for the study. Cardiovascular autonomic dysfunction was determined based on abnormal values in at least two of five non-invasive tests: Valsalva manoeuver, heart rate variation during deep breathing, heart rate response to standing, blood pressure response to sustained hand grip, and blood pressure response to standing. The subjects were subsequently evaluated with electrocardiography. Sickle cell anaemia patients with CAN had statistically significantly increased P-wave duration (p < 0.001), PR-interval (p < 0.05) and QTc dispersion (p < 0.05) compared with patients without CAN. Significantly increased frequencies of Q waves and first degree atrio-ventricular block were found in patients with CAN than in those without CAN (p = 0.026, p = 0.014, respectively). Significant correlations were noted between the severity of CAN [number of abnormal autonomic function tests (AFT)] and (1) P-wave duration (p = 0.008), (2) PR- interval (p = 0.013). Significant association was found between the number of abnormal AFT and (1) presence of Q-waves, and (2) degree of anaemia (haematocrit class). Electrocardiographic features consistent with atrio-ventricular and ventricular repolarization abnormalities are associated with CAN in sickle cell anaemia. Further studies are required to evaluate the prognostic implications of these findings in sickle cell patients with cardiovascular autonomic dysfunction.


Influences of maternal factors on the estimate of genetic parameters for goat feed efficiency traits.
The objective of the present study was to estimate the genetic parameters for the feed efficiency traits in Barbari goats. The data records of 9332 progenies born to 413 sires and 2580 dams were collected with respect to the average daily weight gain (ADG), i.e., ADG1 (birth to weaning), ADG2 (weaning to 6 months), ADG3 (6 to 12 months), as well as derived trait Kleiber ratio (KR), i.e., KR1 (ADG1/3MW0.75), KR2 (ADG2/6MW0.75), and KR3 (ADG3/12MW0.75). The data were corrected for fixed covariates like period of kidding, the season of birth, sex, type of birth, and parity. Univariate and multivariate animal models with an average information function of restricted maximum likelihood (REML) were used to estimate genetic factors for these traits. The best model was evaluated based on the likelihood ratio test. The direct heritability estimates were 0.21 ± 0.03, 0.17 ± 0.03, 0.23 ± 0.04, 0.22 ± 0.04, 0.16 ± 0.04, and 0.26 ± 0.04 for ADG1, ADG2, ADG3, KR1, KR2, and KR3, respectively. However, they were inflated due to high and negative estimates of covariance between direct animal and maternal genetic effects. Moderate estimates of heritability augur the scope for improvement for feed efficiency traits. The maternal genetic effects (m2) significantly contributed to 3-12% of the total phenotypic variance. The realized heritability of mass selection, which takes into account direct and maternal genetic variance together, shows a low to moderate estimate of genetic variance for ADG and KR. The genetic correlation ranged from - 0.48 ± 0.11 (ADG1-KR3) to 0.95 ± 0.00 (ADG1-KR1), phenotypic correlation ranged from - 0.28 ± 0.01 (ADG2-KR3) to 0.94 ± 0.01 (ADG1-KR1), maternal genetic correlation ranged from - 0.22 (KR2-KR3) to 0.96 (ADG1-KR1) and - 0.69 (ADG1-KR3) to 0.95 (ADG1-KR1) for the maternal permanent environment, respectively. Kids can be indirectly chosen for higher feed efficiency since ADG and their associated KR have substantial genetic correlations. It is suggested that the KR should be used as a selection criterion for Barbari goats for improving feed efficiency.


Ophthalmoscopic changes in a patient with Wilson's disease during long-term penicillamine therapy.
The development of retinal pigment epithelial defects in a young patient with Wilson's disease after long-term penicillamine therapy is described. It is hypothesized that decreased copper availability secondary to penicillamine therapy may result in defective elastin within the lamina of Bruch with resultant defects in the overlying retinal pigment epithelium.


Developmental delay in moderately preterm-born children with low socioeconomic status: risks multiply.
To assess separate and joint effects of low socioeconomic status (SES) and moderate prematurity on preschool developmental delay. Prospective cohort study with a community-based sample of preterm- and term-born children (Longitudinal Preterm Outcome Project). We assessed SES on the basis of education, occupation, and family income. The Ages and Stages Questionnaire was used to assess developmental delay at age 4 years. We determined scores for overall development, and domains fine motor, gross motor, communication, problem-solving, and personal-social of 926 moderately preterm-born (MP) (32-36 weeks gestation) and 544 term-born children. In multivariable logistic regression analyses, we used standardized values for SES and gestational age (GA). Prevalence rates for overall developmental delay were 12.5%, 7.8%, and 5.6% in MP children with low, intermediate, and high SES, respectively, and 7.2%, 4.0%, and 2.8% in term-born children, respectively. The risk for overall developmental delay increased more with decreasing SES than with decreasing GA, but the difference was not statistically significant: OR (95% CI) for a 1 standard deviation decrease were: 1.62 (1.30-2.03) and 1.34 (1.05-1.69), respectively, after adjustment for sex, number of siblings, and maternal age. No interaction was found except for communication, showing that effects of SES and GA are mostly multiplicative. Low SES and moderate prematurity are separate risk factors with multiplicative effects on developmental delay. The double jeopardy of MP children with low SES needs special attention in pediatric care.


Association between adiponectin gene polymorphisms and coronary artery disease across different populations.
Many studies have suggested that adiponectin gene might be involved in the development of coronary artery disease (CAD). However, the results have been inconsistent. In this study, the authors performed a meta-analysis to assess the associations of +45T/G, +276G/T and -11377C/G polymorphisms in adiponectin gene with CAD susceptibility. Published literature from PubMed and EMBASE databases were searched. Pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated using fixed- or random-effects model. Sixteen studies (4394 cases / 8187 controls) for +45T/G polymorphism, fifteen studies (3569 cases / 7463 controls) for +276G/T polymorphism, and thirteen studies (3531 cases / 7072 controls) for -11377C/G polymorphism were included in the meta-analysis. The overall results showed that there was a statistically significant association between -11377C/G polymorphism and CAD (G vs. C: OR=1.15, 95%CI 1.07-1.24).Similar results were observed among European (G vs. C: OR=1.11, 95%CI 1.02-1.20) and East Asian populations (G vs. C: OR=1.27, 95%CI 1.11-1.45). However, no significant association was found for +45T/G or +276G/T polymorphism with CAD susceptibility. The meta-analysis indicated the significant association of -11377C/G polymorphism, but not +45T/G or +276G/T polymorphism, with CAD susceptibility. However, large-scale studies with the consideration of gene-gene and gene-environment interactions should be conducted to investigate the associations in future.


An evaluation of the population characteristics, semen quality, and utilization status of autologous sperm cryopreservation and fertility preservation in for 662 patients: a 6-year monocentric retrospective study.
Sperm cryopreservation is an effective method of fertility preservation for disease-related and social sperm freezing. In total, 662 subjects (range: 15-65 years-of-age; mean: 33.49 ± 8.79 years-of-age) were included in this study to investigate the population characteristics, semen quality, and usage of autologous sperm preservation patients in Beijing. Of these, 351 were cancer patients (53.02%, 31.14 ± 7.32 years-of-age) and 311 were non-cancer patients (46.98%, 36.14 ± 9.54 years-of-age). We found that the number of preservation cases increased steadily from 2015 to 2019; 89.73% of these had a bachelor's degree or above; 54.83%, 41.54%, and 3.63% were single, married, and divorced, respectively. The cases of cancers and oligozoospermia accounted for 71.30% of all patients; therefore, most patients required fertility preservation due to disease. The cancer group had a significantly lower sperm concentration, rate of progressive sperm after the frozen-thawed test, total progressive motility sperm count after the frozen-thawed test, and recovery rate of progressive motile sperm (RRPM) than the non-cancer group (all P < 0.05). Sperm count-related parameters were significantly affected by testicular cancer, while sperm motility-related parameters and RRPM were significantly affected by leukemia. The utilization rate of preserved sperm was 6.34% after 6 to 78 months of follow-up. In terms of fresh or frozen embryo transfer, the clinical pregnancy rate was 56.76% or 50.00%, and the live birth rate was 24.32% or 21.43%, respectively. The need for autologous sperm preservation was dominated by patients with diseases, followed by the need for social sperm freezing. Tumors had a major negative impact on semen quality, and the usage rates of stored semen were at lower level compared to the number of sperm cryopreservation. Medical staff and patients should pay attention to both cognition-action consistency and cost-effectiveness in fertility preservation.


Implicit development of gaze strategies support motor improvements during action encoding training of prosthesis use.
Action observation training has been suggested to facilitate motor improvements in the lives of persons with neural injury. Previous studies have shown that for persons with upper limb amputation, matched limb training, where prosthesis users emulate each other, has shown promise above mismatched training where a prosthesis user emulates actions of a person with sound limbs (most commonly that of a therapist). The mechanism underlying the matched limb training benefit is unclear. Gaze strategies may reveal unique patterns between matched and mismatched training which could explain improvements in motor function in matched limb training. Twenty persons with sound limbs were trained on how to use a prosthesis simulator using matched or mismatched limb training in a single session. Eye movements were recorded during the training phase. Kinematics were recorded as persons performed the task. Gaze patterns showed differences between the training groups. The mismatched group demonstrated a higher probability of gaze on the path between the start and end of the action, while the matched group demonstrated a significantly higher probability of focusing on the elements of the path of the action and a trend of focusing on the shoulders. Kinematics also revealed overall improvements in motor control for the matched group. This study proposes a putative mechanism that may explain improvements in matched limb training through shifting gaze strategies. Further work is needed to understand whether implicit visual strategies seen during matched limb training might encourage motor learning during functional training with prostheses.


Phosphorylation of the phosphatase modulator subunit (inhibitor-2) by casein kinase-1. Identification of the phosphorylation sites.
The isolated modulator subunit of the inactive protein phosphatase-1 is phosphorylated in vitro by casein kinase-1 at two different sites: Ser-86 and Ser-174. The Ser-86 site is a common target for casein kinase-1 and casein kinase-2, but is preferentially phosphorylated by the former enzyme. The Ser-174 site seems to be specific for casein kinase-1, and is phosphorylated at a slower rate. These results give a new insight into the in vitro phosphorylation pattern of the modulator subunit of the phosphatase and provides additional data on the specificity of casein kinase-1.


Mechanisms mediating propofol protection of pulmonary epithelial cells against lipopolysaccharide-induced cell death.
Propofol (2,6-diisopropylphenol) is an anaesthetic agent with anti-oxidant properties. The aim of the present study was to determine whether propofol can protect pulmonary epithelial (A549) cells against lipopolysaccharide (LPS)-induced cell death and, if so, the mechanisms involved. The effects of LPS alone and in combination with propofol on A549 cell death were investigated. Cell viability was determined using the colourimetric 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Apoptotic A549 cells were detected by flow cytometry, as propidium iodide-negative and annexin-V-positive cells, and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL). Mitochondrial membrane potential (MMP), caspase 9 activity, Ca(2+) concentrations and reactive oxygen species (ROS) were analysed by immunofluorescent methods. Aconitase 2 (ACO2), microtubule-associated light chain 3 (LC3) and beclin-1 levels were evaluated using reverse transcription-polymerase chain reaction and/or western blot analysis. Exposure of A549 cells to 1-50 μg/mL LPS for 3-24 h resulted in the concentration- and time-dependent induction of cell death. Cell apoptosis accounted for approximately 77% of cell death induced by LPS. Propofol (5-150 μmol/L) concentration-dependently inhibited LPS-induced A549 cell death. This protective effect of propofol was accompanied by prevention of LPS-induced mitochondrial dysfunction (reductions in MMP, ACO2 expression and ATP) and was associated with the inhibition of LPS-induced activation of apoptotic signals (caspase 9 activity, ROS overproduction and Ca(2+) accumulation). In addition, propofol blocked LPS-induced overexpression of the autophagy-associated proteins LC3 and beclin-1. The data indicate that propofol protects A549 cells against LPS-induced apoptosis, and probably autophagy, by blocking LPS-induced activation of ROS/caspase 9 pathways and upregulation of LC3 and beclin-1, respectively.


Blunted HPA axis response to stress is related to a persistent Dysregulation Profile in youth.
The Child Behavior Checklist Dysregulation Profile (DP) in youth has been shown to be a predictor of psychopathology later in life. We examined the activity of the hypothalamic pituitary adrenal (HPA) axis in youth with remitted, new, persistent, and no DP. Data from 489 youth (47% boys) participating in a Dutch longitudinal general population study were included (Wave 1 mean age=11.5, Wave 2=14.2). Wave 2 diurnal cortisol patterns and levels in response to a laboratory stress paradigm were compared in youth with DP at Wave 1 only, Wave 2 only, both Waves, and neither Wave. Youth with the DP at Wave 2 only or at both time points showed blunted cortisol responses to stress relative to the other two groups. There were no group or sex differences in diurnal cortisol activity. More research is needed to determine how the association between DP symptoms and HPA axis functioning changes over time.


A minimum component AM transmitter to monitor electronic brain stimulation.
Construction of a light weight AM transmitter which can be used to monitor implanted electronic brain stimulators is described. The unit can operate continuously for 40 hours on a single battery and can easily be carried by a small laboratory animal. The range of the unit is limited to approximately 1 meter and the transmitted signal can be detected by a standard AM broadcast band receiver. The unit is simple to construct, inexpensive, and reliable in performance.


The Rcs regulon in Proteus mirabilis: implications for motility, biofilm formation, and virulence.
The overall role of the Rcs phosphorelay in Proteus mirabilis is largely unknown. Previous work had demonstrated that the Rcs phosphorelay represses the flhDC operon and activates the minCDE cell division inhibition system. To identify additional cellular functions regulated by the Rcs phosphorelay, an analysis of RNA-seq data was undertaken. In this report, the results of the RNA-sequencing are discussed with an emphasis on the predicted roles of the Rcs phosphorelay in swarmer cell differentiation, motility, biofilm formation, and virulence. RcsB is shown to activate genes important for differentiation and fimbriae formation, while repressing the expression of genes important for motility and virulence. Additionally, to follow up on the RNA-Seq data, we demonstrate that an rcsB mutant is deficient in its ability to form biofilm and exhibits enhanced virulence in a Galleria mellonella waxworm model. Overall, these results indicate the Rcs regulon in P. mirabilis extends beyond flagellar genes to include those involved in biofilm formation and virulence. Furthermore, the information presented in this study may provide clues to additional roles of the Rcs phosphorelay in other members of the Enterobacteriaceae.


Rapid monoclonal antibody adsorption on dextran-grafted agarose media for ion-exchange chromatography.
The binding capacity and adsorption kinetics of a monoclonal antibody (mAb) are measured for experimental cation exchangers obtained by grafting dextran polymers to agarose beads and compared with measurements for two commercial agarose-based cation exchangers with and without dextran grafts. Introduction of charged dextran polymers results in enhanced adsorption kinetics despite a dramatic reduction of the accessible pore size as determined by inverse size-exclusion chromatography. Incorporation of neutral dextran polymers in a charged agarose bead results instead in substantially lower binding capacities. The effective pore diffusivities obtained from batch uptake curves increase substantially as the protein concentration is reduced for the resins containing charged dextran grafts, but are much less dependent on protein concentration for the resins with no dextran or uncharged dextran grafts. The batch uptake results are corroborated by microscopic observations of transient adsorption in individual particles. In all cases studied, the adsorption kinetics is characterized by a sharp adsorption front consistent with a shell-progressive, diffusion limited mechanism. Greatly enhanced transport rates are obtained with an experimental resin containing charged dextran grafts with effective pore diffusivities that are 1-9 times larger than the free solution diffusivity and adsorption capacity approaching 300 mg/cm3 of particle volume.


Client evaluation of community mental health services: relation to demographic and treatment variables.
Community mental health center (CMHC) outpatient clients' satisfaction and perceived problem improvement were assessed by telephoning 108 clients, representing 40% of clients discharged during the period under investigation. The CMHC's services were perceived positively, and most clients were satisfied with their therapy experience, found it helpful, and felt more able to handle future problems. Data on reasons for termination, expected future behavior, and extratherapeutic factors were also gathered. Of particular interest were the findings that satisfaction and improvement were unrelated to client age, sex, marital status, or social class, but significantly more positive outcome responses were found for those clients who terminated therapy with a mutual client--therapist decision as compared to those who terminated unilaterally.


Facile preparation of aminosilane-alginate hybrid beads for enzyme immobilization: Kinetics and equilibrium studies.
A simple, facile and potential platform for enzyme immobilization using alginate-based beads has been demonstrated by simultaneous gelation and modification of alginate using calcium chloride (CaCl2) and 3-aminopropyltriethoxysilane (APTES). In this method, sodium alginate solution containing enzyme was simply dripped into a crosslinker solution containing CaCl2 and APTES, leading to the formation of APTES-alginate hybrid beads (AP-beads). The optical observation, FT-IR analysis and amino group measurements provided evidence that APTES was successfully adsorbed to the alginate chain via electrostatic interaction. On the assumption that the binding of Ca2+ ion to polymannuronate residues of alginate via bidentate bridging coordination is competitive with APTES, the equilibrium isotherm and kinetics for the adsorption of APTES to AP-beads was found to follow extended Langmuir isotherm in binary system. Formate dehydrogenase (FDH) as a model enzyme was successfully immobilized in AP-beads and the immobilization yield of ca. 100% could be achieved under optimal conditions of CaCl2 and APTES concentrations in crosslinker solution. Furthermore, the AP-beads were reused efficiently for 9 cycles without loss of FDH activity. The above results demonstrated that AP-beads were effective support for enzyme immobilization.


Antibacterial Role of SO(4), NO(3), C(2)O(4) and CH(3)CO(2) Anions on Cu(II) and Zn(II) Complexes of a Thiadiazole-derived Pyrrolyl Schiff Base.
A condensation reaction of 2-amino-1,3,4-thiadiazole with 2-pyrrolecarboxaldehyde to form tridentate NNN donor Schiff base has been performed. The prepared Schiff base was further used for the formation of metal complexes having stoichiometry [M(L)(2)]X(n), where M=Cu(II) or Zn(II), L=N-(2-pyrrolylmethylene)-2-amino-1,3,4-thiadiazole, X=SO(4) (2-), NO(3) (-), C(2)O(4) (2-) or CH(3)CO(2-) and n=1 or 2. The new compounds described here have been characterized by their physical, spectral and analytical data, and have been screened against several bacterial strains such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The antibacterial potency of the Schiff base increased upon chelation/complexation, having the same metal ion (cation) but different anions opening up a novel approach in finding new ways to fight against antibiotic resistant strains.


ALDH2 mediates the dose-response protection of chronic ethanol against endothelial senescence through SIRT1/p53 pathway.
Aldehyde dehydrogenase 2 (ALDH2) plays essential roles in drinking-associated diseases or effects. As we have previously reported, ALDH2 mediates acute ethanol-induced eNOS activation in vitro. However, whether chronic ethanol treatment has a dose-response endothelial protection, as well as the possible mediating role of ALDH2 involved, is unclear. Here, we show that appropriate dose of ethanol preserved the expression and activity of ALDH2 and eNOS, and alleviated senescence-associated phenotypes in human aortic endothelial cells. Furthermore, ALDH2 deficiency impairs the dose-response protection of ethanol against endothelial senescence by promoting the accumulation of 4-HNE, the formation of 4-HNE-SIRT1 protein adducts and the subsequent decrease in SIRT1-dependent p53 deacetylation. Collectively, our data indicate that ALDH2 mediates the protection of appropriate ethanol by modulating SIRT1/p53-dependent endothelial senescence.


Interrelation between ROS and Ca2+ in aging and age-related diseases.
Calcium (Ca2+) and reactive oxygen species (ROS) are versatile signaling molecules coordinating physiological and pathophysiological processes. While channels and pumps shuttle Ca2+ ions between extracellular space, cytosol and cellular compartments, short-lived and highly reactive ROS are constantly generated by various production sites within the cell. Ca2+ controls membrane potential, modulates mitochondrial adenosine triphosphate (ATP) production and affects proteins like calcineurin (CaN) or calmodulin (CaM), which, in turn, have a wide area of action. Overwhelming Ca2+ levels within mitochondria efficiently induce and trigger cell death. In contrast, ROS comprise a diverse group of relatively unstable molecules with an odd number of electrons that abstract electrons from other molecules to gain stability. Depending on the type and produced amount, ROS act either as signaling molecules by affecting target proteins or as harmful oxidative stressors by damaging cellular components. Due to their wide range of actions, it is little wonder that Ca2+ and ROS signaling pathways overlap and impact one another. Growing evidence suggests a crucial implication of this mutual interplay on the development and enhancement of age-related disorders, including cardiovascular and neurodegenerative diseases as well as cancer.


High-quality genome sequence and description of Paenibacillus dakarensis sp. nov.
Strain FF9T was isolated in Dakar (Senegal) from a blood-culture taken from a 16-month-old child. MALDI-TOF analysis did not allow for identification. After sequencing, strain FF9T exhibited 98.18% similarity with the 16SrRNA sequence of Paenibacillus uliginis. A polyphasic study of phenotypic and genomic analyses showed that strain FF9T is Gram variable, catalase-positive, and presents a genome of 4,569,428 bp (one chromosome but no plasmid) with 4,427genes (4,352 protein-coding and 75 RNA genes (including 3 rRNA operons). The G+C content is 45.7%. On the basis of these genomic and phenotypic data analyses, we propose the creation of Paenibacillus dakarensis strain FF9T.


Intraosseous pressure measurement during iliac bone marrow biopsy: its feasibility and difference of IOP in diseased marrow and non-diseased marrow.
The purposes of this study were (1) to establish the feasibility and safety of an imaging-guided technique for intraosseous pressure (IOP) measurement in a large cohort of patients, and (2) to compare IOP values between normal and diseased bone marrow. Adult patients undergoing CT-guided marrow biopsy were prospectively and consecutively enrolled from November 2020 to February 2022. IOP measurements were obtained connecting the biopsy needle to a monitoring device using a standard arterial line setup. Clinical data including sex, age and pathology results were obtained. Student t test and Pearson correlation were used for continuous variables comparisons. Univariable analyses were performed using Fisher's exact test. A P value of .05 was considered statistically significant. A total of 139 participants were initially enrolled, and four were excluded during technique optimization. There were no complications related to the measurement technique. Ninety participants (90/135, 67%) had histology confirming marrow pathology. The participants in the diseased marrow group were older than those in the normal marrow group (63 ± 14 vs. 55 ± 14 years; P < .01). There was no difference in mean IOP between both groups (66 ± 23 vs. 64 ± 28 mmHg; P = .69). There was no correlation between mean arterial blood pressure and mean IOP (P = .08). There was no difference in IOP measurements between patients with normal and diseased marrow undergoing CT-guided biopsy. IOP does not appear to be influenced by systemic blood pressure. No complication occurred during the procedures.


Two CcCCL19bs orchestrate an antibacterial immune response in Yellow River carp (Cyprinus carpio haematopterus).
Chemokines are a group of chemotactic cytokines with an essential role in homeostasis as well as immunity via specific G protein-coupled receptors and atypical receptors. In our study, two Yellow River carp (Cyprinus carpio haematopterus) CCL19b genes (CcCCL19bs), tentatively named CcCCL19b_a and CcCCL19b_b, were cloned. The open reading frames (ORFs) of CcCCL19b_a and CcCCL19b_b were both 333 bp that encoded a 12 kDa protein with 110 amino acid residues. CcCCL19bs contained a signal peptide and a SCY domain with four typical conserved cysteine residues. The two CcCCL19b proteins shared high similarities with each other in both secondary and three-dimensional structure. Phylogenetic analysis showed that CcCCL19bs and other CCL19bs from tetraploid cyprinid fish were clustered into one clade. CcCCL19bs were highly expressed in gill and intestine in healthy fish, and a significant up-regulation of gene expression after Aeromonas hydrophila infection and poly(I:C) stimulation was observed in gill, liver, and head kidney. Furthermore, chemotaxis and antibacterial activity of CcCCL19bs were studied. The results indicated that recombinant CcCCL19b_a and CcCCL19b_b protein (rCcCCL19b_a and rCcCCL19b_b) exhibited significant attraction to primary head kidney leukocytes (HKLs). Meanwhile, both of rCcCCL19bs could promote the proliferation of HKLs, and significantly up-regulate the expressions of IL-1β, CCR7, and IL-6, and down-regulate the expression of IL-10 in primary HKLs. In vitro, rCcCCL19bs could bind and aggregate A. hydrophila and Staphylococcus aureus. The rCcCCL19bs exhibited significant antibacterial activity against A. hydrophila, but not S. aureus. Moreover, they inhibited the growth of A. hydrophila and S. aureus. In vivo, overexpression of CcCCL19bs contributed to the bacterial clearance. These studies suggested that CcCCL19bs orchestrate an antibacterial immune response.


The preparation of pyrogen-free foetal calf serum for use in cell and tissue cultured.
A method is described for the preparation of foetal calf serum from blood drawn by heart puncture from calf foetuses obtained from a local municipal abattoir. This method differs from that previously described in that the Seitz Supra EK filter pads used in preliminary purification steps have been abandoned. These pads contain significant amounts of pyrogenic bacterial lipopolysaccharides and attempts to depyrogenate them with sodium hypochlorite, hydrogen peroxide and 1% foetal calf serum were unsuccessful. The modified method uses pyrogen-free glass fibre and cellulose fibre filters and provides an entirely satisfactory serum as proved by negative Limulus amoebocyte lysate tests and the excellent growth of cells.


Using invariom modelling to distinguish correct and incorrect central atoms in `duplicate structures' with neighbouring 3d elements.
Modelling coordination compounds has been shown to be feasible using the invariom method; for the best fit to a given set of diffraction data, additional steps other than using lookup tables of scattering factors need to be carried out. Here such procedures are applied to a number of `duplicate structures', where structures of two or more supposedly different coordination complexes with identical ligand environments, but with different 3d metal ions, were published. However, only one metal atom can be plausibly correct in these structures, and other spectroscopic data are unavailable. Using aspherical scattering factors, a structure can be identified as correct from the deposited Bragg intensities alone and modelling only the ligand environment often suffices to make this distinction. This is not possible in classical refinements using the independent atom model. Quantum-chemical computations of the better model obtained after aspherical-atom refinement further confirm the assignment of the element in the respective figures of merit.


Long-term impairment attributable to congenital cytomegalovirus infection: a retrospective cohort study.
This study aimed to estimate long-term impairment attributable to congenital cytomegalovirus infection (cCMV). This nationwide cohort study retrospectively assessed cCMV in children born in 2008 in the Netherlands, testing 31 484 stored neonatal dried blood spots. Extensive medical data of cCMV-positive children (n=133) and matched cCMV-negative comparison children (n=274) up to 6 years of age were analysed. Moderate to severe long-term impairment was diagnosed in 24.8% (33 out of 133) of all cCMV-positive children (53.8% in symptomatic, 17.8% in asymptomatic), compared with 12.0% (33 out of 274) of cCMV-negative children. Sensorineural hearing loss was seen only in five cCMV-positive children (3.8%). Developmental delays were diagnosed more often in cCMV-positive children than cCMV-negative children: motor (12.0% vs 1.5%), cognitive (6.0% vs 1.1%), and speech-language (16.5% vs 7.3%). Long-term impairment in multiple domains was more frequent in symptomatic (19.2%) and asymptomatic (8.4%) cCMV-positive children than cCMV-negative children (1.8%). Children with cCMV were twice as likely to have long-term impairment up to the age of 6 years, especially developmental delays and sensorineural hearing loss, than cCMV-negative comparison children, with a risk difference of 12.8%. These insights into the risk of cCMV-associated impairment can help optimize care and stimulate preventive measures. Congenital cytomegalovirus infection (cCMV) leads to impairment in 25% of cases. Fifty per cent of children with cCMV symptoms at birth have long-term impairment. The risk difference of moderate to severe long-term impairment between children with and without cCMV is 13%, attributable to cCMV. cCMV leads to motor, cognitive, and speech-language developmental delay in children.


FAM21 directs SNX27-retromer cargoes to the plasma membrane by preventing transport to the Golgi apparatus.
The endosomal network maintains cellular homeostasis by sorting, recycling and degrading endocytosed cargoes. Retromer organizes the endosomal sorting pathway in conjunction with various sorting nexin (SNX) proteins. The SNX27-retromer complex has recently been identified as a major endosomal hub that regulates endosome-to-plasma membrane recycling by preventing lysosomal entry of cargoes. Here, we show that SNX27 directly interacts with FAM21, which also binds retromer, within the Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) complex. This interaction is required for the precise localization of SNX27 at an endosomal subdomain as well as for recycling of SNX27-retromer cargoes. Furthermore, FAM21 prevents cargo transport to the Golgi apparatus by controlling levels of phosphatidylinositol 4-phosphate, which facilitates cargo dissociation at the Golgi. Together, our results demonstrate that the SNX27-retromer-WASH complex directs cargoes to the plasma membrane by blocking their transport to lysosomes and the Golgi.


Olaparib-induced Apoptosis Through EBNA1-ATR-p38 MAPK Signaling Pathway in Epstein-Barr Virus-positive Gastric Cancer Cells.
Epstein-Barr virus (EBV)-associated gastric cancer has been identified as a cancer subtype with definitive clinical and molecular characteristics. Although olaparib, a poly ADP ribose polymerase (PARP) inhibitor, is considered a potential effective agent for gastric cancer, the effect and underlying mechanism of olaparib on gastric cancer depending on EBV infection is not fully understood. EBV-positive SNU719 and EBV-negative SNU638 gastric cancer cell lines were used to identify the effects of olaparib using the trypan blue exclusion method and annexin V staining assay. To observe the underlying cellular signaling mechanisms of olaparib-induced cell death, Epstein-Barr virus nuclear antigen 1 (EBNA1) and signaling related molecule expression were assessed using transfection, silencing of specific genes using small interfering RNA (siRNA), western blotting and signaling inhibition assay. Olaparib decreased the cell viability of EBV-positive SNU719 gastric cancer cells through caspase-3-dependent apoptosis in a dose dependent manner, whereas EBV-negative SNU638 gastric cancer cells showed drug resistance to olaparib. EBNA1 was expressed in SUN719 gastric cancer cells; however, ataxia telangiectasia and Rad3 related (ATR) and phosphorylated ATR kinase were expressed in SNU638 gastric cancer cells. EBNA1 transfection decreased ATR phosphorylation through p38 mitogen-activated protein kinase (MAPK) phosphorylation in SUN638 gastric cancer cells, and silencing of ATR kinase increased the susceptibility of these cells to olaparib treatment. Moreover, VE-821, an ATR kinase specific inhibitor, also increased the sensitivity of SNU638 cells to olaparib. In contrast, SB203580, a p38 MAPK inhibitor, inhibited this increase in sensitivity to olaparib by EBNA1 transfection. Olaparib treatment led to different cellular responses depending on EBV infection in gastric cancer cell lines. These results provide new insights into the mechanism of olaparib-induced apoptosis in gastric cancer cells and suggest that EBV infection should be considered when developing new potential therapeutic agents for gastric cancer.


Antibodies to Plasmodium falciparum sporozoites following a malarial outbreak in a non-endemic area of Sri Lanka.
An enzyme-linked immunosorbent assay (ELISA) based on the synthetic peptide (NANP)40 was used to characterize the sporozoite antibodies in an unusual Plasmodium falciparum outbreak in a non-malarious area in Sri Lanka. A positive antibody response was seen in 62% of patients with their first P. falciparum illness. There was no correlation between sporozoite antibodies and the antibody against blood stages, determined by immunofluorescence assay. The majority (91%) of the patients lost the antibodies to circumsporozoite (CS) protein within one year (in the absence of re-exposure). Three patients had high levels of CS antibodies even after one year, and this persistence was related to the level of the initial antibody response. In the area of the outbreak 10% of schoolchildren had antibodies to the (NANP)40 peptide. 21% of the 42 children with present or past overt malaria were antibody positive. Of the children with no such background, 8% were antibody positive. The corresponding seropositivity rates for asexual blood stages were 31% and 1% for the 2 groups respectively. It is concluded that (NANP)40 ELISA is potentially a valuable tool in sero-epidemiology, particularly in situations of seasonal transmission and recurrences due to drug resistance.


Modification of skeletal S-1 with fluorescein isothiocyanate.
1. Pyridoxal-5'-phosphate (PLP), a marker of primary amines, bound covalently to S-1 in an approximate ratio of 1:1. PLP was localized within the tryptic 25,000 mol. wt fragment. 2. Fluorescein isothiocyanate (FITC), which is known to bind covalently to primary amino groups located at nucleotide binding sites, readily bound to S-1 in a 2:1 ratio. FITC was localized within the 20,000 and 50,000 mol. wt tryptic peptides, in a ratio of 1:1 in each one. 3. These results are consistent with the existence of nucleotide binding sites on myosin different from those of the catalytic sites.


[Sachse internal urethrotomy: endoscopic treatment of urethral strictures].
The most commonly used treatment modality for urethral strictures is the direct visual internal urethrotomy (DVUI) method according to Sachse. It is an effective short-term treatment, but the long-term success rate is low. A number of factors influence the outcome of DVUI including stricture location, spongiofibrosis and previous endoscopic stricture treatment. Multiple urethrotomy has a negative impact on the success rate of subsequent urethroplasty. A thorough preoperative diagnostic work-up including combined retrograde urethrogram/voiding cystourethrogram (RUG/VCUG) and urethrocystoscopy is, therefore, mandatory to allow for patient counselling regarding the risk of stricture recurrence and other treatment options. After a failed primary DVUI, subsequent urethrotomy cannot be expected to be curative.


[Final voluntary assessment for Traumatology and Orthopaedic Surgery medical residents: a report on the results and a look at the future].
The idea of establishing an examination that accredits the training of the specialists in orthopaedic surgery at the end of their educational period as residents is subject to controversy. With the aim of encouraging the development of this examination, the present members of the National Commission of the Specialty of Orthopaedics (CNE) have reviewed the results obtained in previous examination. The results of the voluntary final exam for Orthopaedics residents, and of the surveys of participant opinions for the years 2006 to 2011 are presented. The total number of participants was 231, growing from 19 in 2005, to 71 in 2011. The overall mean score in the period reviewed (2006-2011) was 6.72 out of 10 points. In these 6 years, 9 participants failed (4.25%). The mean score for the test was 7.57. The overall mean score of the oral exam was 6.57. The worst results were obtained in the general knowledge section of the oral examination. Nobody has ever failed the section on reconstruction of the lower extremity. The upper extremity section in the oral examination achieves the best average results. The examination has established its place in the structure of orthopaedic resident training in our country, even without making it official by the Administration. We must positively acknowledge those candidates who chose to take the examination and be evaluated by their peers in order to prove their qualification and distinction. This recognition will be the best encouragement for future generations.


Managing Pain in the Older Cancer Patient.
This paper aims to give the specialist and non-specialist alike an overview of the considerations involved in the management of cancer-related pain in the older population. Comprehensive guidelines on cancer pain management have been published recently by expert bodies. Cancer pain differs in many respects to other pain conditions and we are likely to encounter it more frequently in older patients in the future. The elderly are more sensitive to the effects of many analgesic medications. The elderly patient with cancer pain presents a unique challenge to the treating physician. The biological effects of ageing impact on the efficacy of many pain management strategies as well as its diagnosis and assessment. Treatment options can be broadly divided into pharmacological, non-pharmacological and interventional. A multidisciplinary approach and frequent re-assessment are essential in achieving favourable outcomes in this patient group.