Accuracy of ultrasound-guided fine-needle aspiration cytology for diagnosis of carcinoma in patients with multinodular goiter.
Fine-needle aspiration (FNA) is a useful method for evaluating multinodular goiter; however, its role is still controversial. The aim of this study was to assess the utility of ultrasound-guided thyroid FNA in detecting malignancy in patients with multinodular goiter in Oman. This was a retrospective study where all patients with multinodular goiter seen at the Sultan Qaboos University Hospital endocrinology clinic in Oman in 2005 were evaluated. The thyroid FNA results were grouped into either malignancy (positive result) or others (negative result). They were compared to those of final histopathological examination in order to calculate the value of the test in diagnosing malignancy. Analyses were evaluated using descriptive statistics. A total of 272 patients were included in the study. The mean age was 39΁13 years with an age range from 5 to 85 years. The majority of the patients were females (n=236; 87%). The results of thyroid FNA revealed that 6% (n=15) of the patients had malignancies while histopathological results showed that the proportion of subjects with malignancies was 18% (n=49). Out of the 15 cases identified to have malignances by thyroid FNA, only 53% (n=8) of the subjects were confirmed to have malignancy by biopsy. Overall, the results of the tests were poor, revealing a sensitivity of 16%, specificity of 97% and a diagnostic accuracy of 82%, with a positive predictive value of 53% and a negative predictive value of 84%. Thyroid FNA is not a useful test in differentiating multinodular goiter from malignancy, as more than 80% of the malignancies go unnoticed.


Creating an Interdisciplinary Collaborative Network of Scholars in Child Maltreatment Prevention: A Network Analysis of the Doris Duke Fellowships for the Promotion of Child Well-Being.
Child maltreatment is a complex problem requiring interdisciplinary collaborative research to generate innovative solutions. The Doris Duke Fellowships for the Promotion of Child Well-Being were designed to identify and nurture emerging scholars committed to child maltreatment prevention and create a supportive interdisciplinary learning network. This paper examines connectivity within the collaborative network created by the fellowships program using longitudinal social network data. Participants were 120 individuals selected as Doris Duke Fellows during their doctoral training at universities in the United States. Fellows completed annual, voluntary web-based surveys to assess their interactions with other fellows during the past year. Social network analysis methods were used to assess the strength and quality of the learning network over a four-year period. Across four years of data, there were increases in the number of connections, proportion of cross-cohort connections, and proportion of interdisciplinary connections. Network analyses showed a highly connected network consisting of primarily medium- and high-quality connections between fellows from different disciplines. The number of scientific journal articles authored by two or more fellows grew substantially over time. Findings indicate the collaborative network created by the fellowships program is growing and strengthening over time. The new Child Well-Being Research Network extends the fellowships network to a broader group of scholars and professionals to advance diversity, equity, inclusion, and justice in the field of child well-being research.


Enhanced cognitive demodulation with artificial intelligence.
The low-cost 'THz Torch' wireless link technology is still in its infancy. Until very recently, inherent limitations with available hardware has resulted in a modest operational figure of merit performance (Range [Formula: see text] Bit Rate). However, a breakthrough was reported here by the authors, with the introduction of 'Cognitive Demodulation'. This bypassed the thermal time constant constraints normally associated with both the thermal emitter and sensor; allowing step-change increases in both Range and Bit Rate with direct electronic modulation. This paper concentrates on advancements to the bit error rate (BER) performance. Here, separate techniques are introduced to the demodulation software that, when combined, result in enhanced Cognitive Demodulation. A factor of more than 100 improvement in BER was demonstrated within the laboratory and approximately a 60-fold improvement in a non-laboratory environment; both at the maximum Range and Bit Rate of 2 m and 125 bps, respectively, demonstrated recently. Moreover, demodulation speed is increased by almost a factor of 10,000; allowing for real-time demodulation while easing future computational hardware requirements. In addition to these software advancements, the paper demonstrates important improvements in hardware that has brought the technology out of the laboratory, with field trials being performed within an office corridor.


Cell proliferation and DNA-synthesis in the external granular layer of the postnatal rat cerebellum: a quantitative study.
The external granular layer (EGL) of the rat cerebellum can be subdivided into two morphologically distinct zones, the outer of which consists of proliferating cells, while the inner has generally been considered to contain post-mitotic cells exclusively. Two criteria, the detection of mitotic figures and the observation of nuclei labelled shortly after an injection of [3H]-thymidine, were used to locate proliferating cells. Their distribution across the layer was quantified for several ages of animal. Though most frequent superficially, cell proliferation was found to occur at all levels of the EGL. Possible explanations for the existence of a gradient of proliferative activity across the EGL are discussed.


Impact of aortocaval shunt flow on cardiac and renal function in unilateral nephrectomized rats.
We previously reported significantly enhanced cardiac remodeling post aortocaval fistula (AV) in unilateral nephrectomized (UNX) rats. However, the relationship between the size of the AV and the cardiorenal effects in UNX rats remains unknown. In the present study, AV was induced by 20, 18 and 16 gauge needles in UNX rats to see if larger shunt would definitely induce heavier cardiac and renal damage in UNX rats. Our results demonstrated that bigger shunt size is linked with proportional more significant cardiorenal remodeling and dysfunction in UNX rats. Expression of inflammatory biomarkers including CRP, TNF-α, IL-6, IL-1β, TGF-β and MCP-1 in left kidney and heart was significantly increased in all UNX + AV groups compared to Sham rats. Inflammation might thus participate in the worsening cardiorenal functions and remodeling processes in this model.


Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix.
To test the hypothesis that cisplatin (CDDP) administered concurrently with standard radiotherapy (RT) would improve pelvic control and survival in patients with advanced squamous cell cancer of the cervix. A total of 259 patients with International Federation of Gynecology and Obstetrics stage IB to IVA squamous cell cervical cancer with central disease greater-than-or-equal 5 cm or histologically confirmed pelvic lymph node involvement were randomized to receive RT (external-beam RT plus brachytherapy) plus weekly CDDP chemotherapy (40 mg/m(2)) (arm 1) or the same RT without chemotherapy (arm 2). A total of 253 patients were available for analysis. Median follow-up was 82 months. No significant difference was found in progression-free survival (P =.33). No significant difference in 3- and 5-year survival rates was found (69% v 66% and 62% v 58%, respectively; P =.42). The hazard ratio for survival (arm 2 to arm 1) was 1.10 (95% confidence interval, 0.75 to 1.62). This study did not show a benefit to either pelvic control or survival by adding concurrent weekly CDDP chemotherapy in a dose of 40 mg/m(2) to radical RT as given in this trial. Careful attention to RT details is important for achieving optimum outcome for patients with this disease.


A responsive europium(III) chelate that provides a direct readout of pH by MRI.
A europium(III) DO3A-tris(amide) complex is reported for imaging pH by MRI using ratiometric chemical exchange saturation transfer (CEST) principles. Deprotonation of a single phenolic proton between pH 6 and 7.6 results in an ∼5 ppm shift in the water exchange CEST peak that is easily detected by MRI. Collection of two CEST images at two slightly different activation frequencies provides a direct readout of solution pH without the need of a concentration marker.


Projections from the visual cortex to the contralateral claustrum of the cat revealed by an anterograde axonal transport method.
Contralateral projections from visual areas 17, 18, 19 and the Clare-Bishop area of the cerebral cortex to the claustrum have been investigated in the cat using intracortical injections of [3H]proline. Radioactive material was found in a dorsocaudal region of the contralateral claustrum. This region was homotopic with respect to that found for the ipsilateral projection from visual cortex. The contralateral connection is assumed to be a monosynaptic pathway. The pattern by which the corticofugal fibres terminate in the claustrum is quite similar to the one described for the opposite hemisphere [6].


The functional significance of event-related desynchronization of alpha rhythm in attentional and activating tasks.
The functional significance of event-related desynchronization (ERD) of alpha rhythm was investigated in a task which manipulated cognitive load and event rate. It was found that with increasing cognitive load the amount and duration of ERD increased. When a slow event rate was used the mean relative desynchronization of alpha rhythm and duration of ERD increased. These effects were found to be independent of one another. These results were interpreted as indicating that the mean ERD of alpha rhythm is sensitive to the selective attention demands of a task and the surprise value of stimuli.


Allergic conjunctivitis and dry eye syndrome.
Allergic conjunctivitis (AC) and dry eye syndrome (DES) are 2 of the most common anterior inflammatory disorders of the ocular surface and one does not preclude the coexistence of the other. To examine the potential overlap between AC and DES as comorbidities. Using the validated questionnaire known as Subjective Evaluation of Symptom of Dryness, we studied self-reported itchiness, dryness, and redness. In an outpatient optometric setting, 689 patients treated from January 1, 2007, to January 1, 2011, were surveyed for their ocular history and categorized according to their reported level of discomfort of itchiness, dryness, and redness. Patients ranged in age from 5 to 90 years (median age, 25 years; 39.5% male; 60.5% female). In the studied 689 patients, clinically significant itchiness was found in 194 (28.2%), dry eyes in 247 (35.8%), and redness in 194 (28.2%). Symptom overlap was demonstrated in many of the patients. Of the 194 patients with itchiness, 112 (57.7%) had clinically significant dryness. In the 247 patients with dry eyes, 112 (45.3%) had clinically significant itch. Redness was apparent in 120 of the 194 patients with itch (61.9%) and 122 of the 247 patients with dryness (49.4%). Statistical analysis demonstrated that self-reported itchiness, dryness, and redness were not independent of each other (P<.001; Pearson χ(2) test). The odds of patients with "itchy eyes" also experiencing dry eyes were 2.11 times and the odds of these patients also experiencing redness were 7.34 times that of patients with nonitchy eyes. Most patients with "itchy eyes" consistent with AC also have dry eyes and redness. These results suggest that some symptomatic patients concomitantly have features of AC and DES.


Responsiveness of the Persian health assessment questionnaire measures in differentiating among disease activity levels in rheumatoid arthritis patients.
Evidence suggests that inflammation has a harmful effect on muscle strength as well as on functional disability. The purpose of the present study was to examine the association of objectively measured disease activity levels and functional disability among Iranian patients with Rheumatoid Arthritis (RA), and to analyse whether a Persian version of the health assessment questionnaire-disability index (PHAQ-DI) can distinguish between RA patients at different stages of the disease progression. 198 RA patients were requested to complete the PHAQ-DI. The disease activity score for each patient was evaluated using the disease activity score (DAS-28). The association analysis between the PHAQ-DI scores and the four levels of disease activity was measured using a Spearman correlation coefficient. A Kruskal-Wallis analysis was utilized to determine differences in PHAQ-DI scores among the levels of disease activity. The Receiver operating characteristic (ROC) curve was also utilized to determine the PHAQ-DI total score cut-off for predicting the level of disease activity. Spearman's correlation coefficients between the PHAQ-DI and the disease activity level ranged between 0.59 and 0.75. There were significant differences in the PHAQ-DI total score among known groups with various disease activity levels (P = 0.001); However, HAQ-DI total score could not differentiate the remission phase from low disease activity levels in patients with RA (p = 0.37). The PHAQ-DI total score cut-off for distinguishing remission-low disease activity from moderate-high disease activity was 1.19, with a specificity of 0.91 and a sensitivity of 0.615. The present findings provide evidence for the degree to which the PHAQ-DI measures identify and distinguish disease activity levels in patients with rheumatoid arthritis. The PHAQ-DI questionnaire, as a patient-administered, non-invasive, fast, inexpensive and available tool, can be used in the rheumatologist's office as a substitute for determining disease activity in patients with active RA.


CBDB: the codon bias database.
In many genomes, a clear preference in the usage of particular codons exists. The mechanisms that induce codon biases remain an open question; studies have attributed codon usage to translational selection, mutational bias and drift. Furthermore, correlations between codon usage within host genomes and their viral pathogens have been observed for a myriad of host-virus systems. As such, numerous studies have investigated codon usage and codon bias in an effort to better understand how species evolve. Numerous metrics have been developed to identify biases in codon usage. In addition, a few data repositories of codon bias data are available, differing in the metrics reported as well as the number and taxonomy of strains examined. We have created a new web resource called the Codon Bias Database (CBDB) which provides information regarding the codon bias within the set of highly expressed genes for 300+ bacterial genomes. CBDB was developed to provide a resource for researchers investigating codon bias in bacteria, facilitating comparisons between strains and species. Furthermore, the site was created to serve those studying adaptation in phage; the genera selected for this first release of CBDB all have sequenced, annotated bacteriophages. The annotations and sequences for the highly expressed gene set are available for each strain in addition to the strain's codon bias measurements. Comparing species and strains provides a comprehensive look at how codon usage has been shaped over evolutionary time and can elucidate the putative mechanisms behind it. The Codon Bias Database provides a centralized repository of look-up tables and codon usage bias measures for a wide variety of genera, species and strains. Through our analysis of the variation in codon usage within the strains presently available, we find that most members of a genus have a codon composition most similar to other members of its genus, although not necessarily other members of its species.


Cervical screening: patients' negative attitudes and experiences.
This article explores the negative attitudes some women have towards the cervical screening programme. These attitudes could ultimately prevent them from participating in the programme. The negative experiences of women who receive a positive result are also explored. Women's negative attitudes towards cervical screening can largely be countered by improving their understanding of the process and diagnosis of cervical cancer. Women who receive a positive smear should be offered support to reduce their anxiety.


Mean occupancy time: linking mechanistic movement models, population dynamics and landscape ecology to population persistence.
Reaction-diffusion models for the dynamics of a biological population in a fragmented landscape can incorporate detailed descriptions of movement and behavior, but are difficult to analyze and hard to parameterize. Patch models, on the other hand, are fairly easy to analyze and can be parameterized reasonably well, but miss many details of the movement process within and between patches. We develop a framework to scale up from a reaction-diffusion process to a patch model and, in particular, to determine movement rates between patches based on behavioral rules for individuals. Our approach is based on the mean occupancy time, the mean time that an individuals spends in a certain area of the landscape before it exits that area or dies. We illustrate our approach using several different landscape configurations. We demonstrate that the resulting patch model most closely captures persistence conditions and steady state densities as compared with the reaction-diffusion model.


Anti-cyclic Citrullinated Peptide Antibody-positive Girl with Chronic Polyarthritis Later Diagnosed with Juvenile Systemic Lupus Erythematosus: A Case Report.
Arthritis is one of the earliest symptoms of juvenile systemic lupus erythematosus (SLE) but is unusual in cases presenting with chronic arthritis or deforming/erosive arthritis. Overlap of juvenile idiopathic arthritis (JIA) and juvenile SLE is a rare clinical condition known as "rhupus" syndrome. The clinical and serological characteristics of rhupus syndrome in children remain to be established. In addition, no studies regarding anti-cyclic citrullinated peptide (CCP) antibody in juvenile SLE or juvenile rhupus syndrome have been reported. A 12-year-old girl suffered from polyarthralgia lasting for one week. She was tentatively diagnosed with polyarticular JIA because of her symptom of chronic arthritis and a positive result for anti-CCP antibody. After six months of follow-up for JIA, she presented with a fever, malar rash, and worsening of arthralgia. Laboratory examinations revealed hypocomplementemia and a positive result for anti-double-stranded DNA antibody. She was diagnosed with juvenile SLE. It is important to note that patients with chronic arthritis, as well as those with anti-CCP antibody-positive polyarthritis, should be carefully followed for their clinical and serological condition, considering the possibility of them developing juvenile SLE.


Major histocompatibility complex-regulated odortypes: peptide-free urinary volatile signals.
Major histocompatibility complex (MHC) genes influence urinary odors (odortypes) of mice. That volatile odorants are involved is supported by the observation that odortype identity can be detected from a distance. Furthermore, chemical analyses of urines have revealed numerous volatile odorants that differ in relative abundance between mice that differ only in MHC genotypes. In addition, urines from MHC-different mice evoke distinct odor-induced activity maps in the main olfactory bulbs. However, recent studies report that non-volatile MHC class I peptides may directly act as MHC-associated signals and may thereby be seen to call into question the evidence for a volatile MHC signal. To evaluate this question, we designed a procedure to collect peptide-free urinary volatiles and tested these volatiles for their ability to mediate chemosensory discrimination of MHC-congenic mice differing in their MHC genotype. The headspace volatiles from urines of C57BL/6 congenic mice (haplotypes H2(b) and H2(k)) were collected by solid phase microextraction (SPME). These volatiles were then desorbed into a gas chromatograph (GC) and the entire chromatographic eluate was collected into a buffer solution. Our results conclusively demonstrate that mice trained to discriminate between unadulterated urinary signals of the congenic mice generalize the discrimination, without reward or training, to the buffer solution containing the peptide-free urinary volatiles (p<0.001, binomial test). Thus volatile signals, perhaps along with non-volatile ones, are capable of mediating behavioral discriminations of mice of different MHC genotypes.


Retrograde transport of [3H]proline: a widespread phenomenon in the central nervous system.
[3H]Proline was injected into spinal cord, pons, inferior colliculus, superior colliculus, lateral geniculate nucleus, pulvinar-LP complex and visual cortex of cats or rats. After 1-3 days' survival the animals were perfused with formalin or mixed aldehydes. Autoradiography showed labeling of cell bodies in most regions known to project to the injection sites. The ability to take up and retrogradely transport [3H]proline appears to be a common property of central neurons. We infer that the transport of this compound is unrelated to its possible status as a neurotransmitter.


Cardiac arrhythmias during nonsynchronized extracorporeal shock wave lithotripsy.
We evaluated the occurrence of cardiac arrhythmias during nonsynchronized extracorporeal shock wave lithotripsy. A total of 125 nonsynchronized shock wave lithotripsy treatments was performed using a spark plug lithotriptor. Asymptomatic unifocal ventricular premature contractions occurred during 23 treatments (18.4%) and were more frequent during therapy on the right side (p < 0.05). Among patients undergoing multiple sessions only 1 exhibited ventricular premature contractions during treatment. No correlation was demonstrated between ventricular premature contractions and patient age, gender, presence of heart disease, stone size and location within the collecting system (kidney or ureter), presence of a ureteral catheter or nephrostomy tube, mode of anesthesia or number of shock waves. Nonsynchronized shock wave lithotripsy can be accomplished safely in most patients.


Embryonic microRNAs are essential for bovine preimplantation embryo development.
MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression after transcription. miRNAs are present in transcriptionally quiescent full-grown oocytes and preimplantation embryos that display a low level of transcription prior to embryonic genome activation. The role of miRNAs, if any, in preimplantation development is not known. The temporal pattern of expression of miRNAs during bovine preimplantation development was determined by small RNA-sequencing using eggs and preimplantation embryos (1-cell, 2-cell, 4-cell, 8-cell, 16-cell, morula, and blastocyst). Embryos cultured in the presence of α-amanitin, which permitted the distinguishing of maternal miRNAs from embryonic miRNAs, indicated that embryonic miRNA expression was first detected at the two-cell stage but dramatically increased during the morula and blastocyst stages. Targeting DGCR8 by a small-interfering RNA/morpholino approach revealed a role for miRNAs in the morula-to-blastocyst transition. Knockdown of DGCR8 not only inhibited expression of embryonically expressed miRNAs but also inhibited the morula-to-blastocyst transition. In addition, RNA-sequencing identified an increased relative abundance of messenger RNAs potentially targeted by embryonic miRNAs in DGCR8-knockdown embryos when compared with controls. Results from these experiments implicate an essential role for miRNAs in bovine preimplantation embryo development.


Emotion Regulation Mediates the Associations of Mindfulness on Symptoms of Depression and Anxiety in the General Population.
In the last decade, clinical research on mindfulness and its positive effects on depression and anxiety have gained increased interest. Emotion regulation mediates the effects of mindfulness on mental health in clinical samples and among meditators. The present study examined whether these associations also generalize to the general population. Multi-group structural equation models tested with a sample of 853 adults whether difficulties in emotion regulation mediated the associations between overall mindfulness in addition to the Observe facet with symptoms of depression and anxiety and whether associations were similar among men and women. Emotion regulation partially mediated the associations of overall mindfulness with symptoms of depression and anxiety; associations with Observe were fully mediated. The magnitude of associations was similar among men and women. Mindfulness exerts positive effects on mental health among the general population mostly via improving emotion regulation. The training of mindfulness and emotion regulation may thus benefit mental health not only in clinical populations but also in the general population. Venues for further research are discussed.


Enantioselective Nozaki-Hiyama-Kishi allylation-lactonization for the syntheses of 3-substituted phthalides.
We report the synthesis of bipyridyl ligands and these ligands were applied in the chromium-catalyzed enantioselective Nozaki-Hiyama-Kishi allylation of substituted (2-ethoxycarbonyl)benzaldehydes and subsequently lactonized to synthesize phthalides with an optimal enantioselectivity of 99%. This approach was applied to synthesize (S)-cytosporone E at a 71% yield in three steps.


The addition of a parent and clinician component to the eating disorder examination for children and adolescents.
Our goal was to evaluate the addition of parent and clinician reports to the eating disorder examination (EDE) when used with children and adolescents. The EDE was completed with 117 children and adolescents with eating disorders (mean age 14.95 +/- 1.91 years). A slightly modified version of the EDE was completed with parents, and clinician summary scores were assigned. Repeated measures analysis was used to compare child, parent, and clinician scores. In those 70 participants with anorexia nervosa (AN) or eating disorder not otherwise specified with a restrictive pattern (EDNOS-R), child scores were significantly lower than parent scores and clinician scores on restraint and weight concerns. On eating concerns and shape concerns, child scores were lower than clinician scores. Participants with bulimia nervosa (BN) or eating disorder not otherwise specified with binge eating or purging (EDNOS-BP), reported more restraint and shape concerns than parents (n = 47), but their scores did not differ from clinician ratings. No differences were seen in this group on weight concerns or eating concerns. Parent and clinician reports are particularly important when assessing children and adolescents with AN or EDNOS-R, but may be less critical for those with BN or EDNOS-BP.


Priority based health data monitoring with IEEE 802.11af technology in wireless medical sensor networks.
In this work, the IEEE 802.11af technology-based wireless sensor network for health data monitoring with priority classes is proposed. In IEEE 802.11af technology, a White Space Device (WSD), a Station (STA), and an Access Point (AP) communicate through television white spectrum opportunistically without causing any harmful interference to licensed` services. In the proposed network; WSDs, STA, and AP employ Frequency Division Multiple Access (FDMA) technique with the aim of communicating through the white space spectrum determined by White Space Map (WSM). WSD collects health data such as body temperature and blood pressure from an implant or on-body sensors. The priority class is determined according to the emergency of a patient as red, yellow, and green. After obtaining the analytical model of the proposed network, the simulation model is carried out using Riverbed Modeler. The graphical results prove the validity and applicability of the proposed network in terms of delay (0.17 s) and energy consumption (4.7 mJ/s) without any spectrum cost for priority-based health data monitoring. Graphical abstract Cognitive radio based IEEE 802.11af environment for priority based health data monitoring.


Neuropathological effect of carbamate molluscicides on the land snail, Eobania vermiculata.
The present study was designed to investigate the neuropathological effect of the two carbamate pesticides: methomyl and methiocarb on the neurons of the buccal ganglia in the land snail Eobania vermiculata using topical application and baiting technique. Their in vivo effects on acetylcholinesterase (AChE, EC 188.8.131.52) activity were also investigated. Sublethal dose and concentration (1/4 LD(50) and 1/4 LC(50)) of both pesticides were used, and the experiment lasted for 14 days. Histopathological and ultrastuctural alterations in the buccal ganglia were more obvious after the baiting technique treatment than after the topical application method, and methomyl was found to be more toxic than methiocarb. These alterations included shrinkage of the perikarya of neurons, increased cytoplasmic basophilia, and extreme indentation of the plasma membrane. In addition, the nuclei appeared karyolitic, eccentric, and highly shrunken with an irregular nuclear envelope. The most outstanding symptom observed after topical application of methiocarb was a highly vacuolated cytoplasm with a peripheral increase in electron density associated with dense accumulations of free ribosomes. On the other hand, an increased number of lysosomes and autophagosomes were observed after topical application of methomyl. Mitochondrial damage, increased number of lipid droplets, and myelin figures were frequently observed in ganglia treated with either methomyl or methiocarb. Moreover, it was noticed that both compounds induced reductions in AChE activity. However, methomyl exhibited more potency in reducing AChE activity than methiocarb.


Optimization of aptamer microarray technology for multiple protein targets.
Aptamer-based microarrays for the quantitation of multiple protein analytes have been developed. A multiplex aptamer microarray was generated by printing two RNA aptamers (anti-lysozyme and anti-ricin) and two DNA aptamers (anti-IgE and anti-thrombin) on to either streptavidin (SA) or neutravidin (NA)-coated glass slides. However, substantial optimization was required in order to ensure the simultaneous function of the aptamer:analyte pairs. The effects of protein labeling, assay buffer, surface coating, and immobilization chemistry and orientation were investigated. A single buffer (PBS buffer containing 5 mM MgCl2 and 0.1% Tween 20) was found to work well with all the aptamers, even though this was not the buffer originally used in their selection, while neutravidin-coated slides yielded a lower detection limit, wider detection range, and more uniform background than streptavidin-coated slides. Incubation with Cy3-labeled proteins yielded sensitive, target-specific, and dose-dependent responses to each protein. Target protein concentrations as low as 72 pg/mL (5 pM, lysozyme), 15 ng/mL (0.5 nM, ricin), 1.9 ng/mL (0.01 nM, IgE), and 170 ng/mL (5 nM, thrombin) could be detected. These results show that aptamer arrays can potentially be used with numerous proteins in parallel, furthering the notion that aptamer arrays may be useful in proteomics.


Neck circumference and future cardiovascular events in a high-risk population--A prospective cohort study.
The distribution of adipose tissue has been evaluated in relation to cardiovascular risk factors and biochemical components of the metabolic syndrome. Neck circumference (NC) has been shown to have a strong relationship with cardiovascular disease (CVD) and may be a novel indicator of CVD. The aim of this study was to compare the incidence of CVD events in cohorts with different NC distributions, and to correlate NC with future CVD events and relative mortality. A prospective cohort study was performed on 12,151 high-risk cardiology outpatients from 2004 until 2014. Anthropometric parameters like body mass index, NC, waist circumference, and hip circumference were measured at baseline and follow-up and compared in different cohorts with high, medium, and low NC. Fatal and non-fatal CVD events were compared in the follow-up study, and survival analysis was conducted. Independent Chi-square tests were performed to compare the incidence of CVD events and mortality among the cohorts and analyze the interactions. The subjects comprised of 6696 women and 5819 men who completed a mean 8.8-year follow-up. All of the participants had two or more CVD risk factors at baseline. At the end of the study, 4049 CVD events had occurred in 2304 participants. The incidence of non-fatal CVD events was 14.08, 16,65, and 25.21 % in the low-NC, medium-NC, and high-NC cohorts, respectively (p < 0.001). The all-cause mortality was 9.77, 11.93, and 19.31 %, and CVD mortality, 4.00, 6.29, and 8.01 %, respectively (p < 0.001). Compared with baseline, the number of CVD risk factors in participants had increased from 2.6, 3.0, and 3.4 to 3.5, 4.1, and 4.7 in the low-, medium-, and high-NC cohorts (34, 36, and 38 %), respectively. The event-free survival rate was 95.32, 80.15, and 75.47 %, respectively. A higher NC indicated a higher incidence of future fatal and non-fatal CVD events and all-cause mortality in both male and female high-risk participants. CVD risk factors increased more in the higher NC group. NC as a novel indicator of CVD showed good predictive ability for CVD events and mortality in a high-risk population.


Molecular difference between WASP and N-WASP critical for chemotaxis of T-cells towards SDF-1α.
Wiskott-Aldrich Syndrome protein (WASP) integrates cell signaling pathways to the actin cytoskeleton, which play a critical role in T-cell activation and migration. Hematopoietic cells express both WASP and neural-WASP (N-WASP) which share similar domain structure, yet WASP deficiency causes Wiskott-Aldrich syndrome, suggesting that N-WASP present in the cells is not able to carry out all the functions of WASP. We have identified a unique internal thirty amino acid region (I30) in WASP, which regulates its function in chemotaxis of Jurkat T-cells. Deletion of the I30 region altered the WASP's closed conformation and impaired its ability to rescue the chemotactic defect of WASP-deficient (Jurkat(WKD)) T-cells. Expression of N-WASP in Jurkat(WKD) T-cells using WASP promoter restored the migration velocity without correcting the chemotactic defect. However, insertion of I30 region in N-WASP (N-WASP-I30) enabled N-WASP to rescue the chemotactic defect of Jurkat(WKD) T-cells. N-WASP-I30-EGFP displayed a punctate localization in contrast to the predominant nuclear localization of N-WASP-EGFP. Thus, our study has demonstrated that the I30 region of WASP is critical for localization and chemotaxis. This suggests that N-WASP's failure to compensate for WASP in rescuing chemotaxis could be due to the absence of this I30 region.


The occurrence of some foodborne pathogens recovered from poultry meat in Shahrekord, Iran.
Arcobacter butzleri, Listeria monocytogenes, Staphylococcus aureus, and Campylobacter jejuni are significant foodborne pathogens regarding the consumption of raw poultry meat. An existing survey was conducted to assess the occurrence of S. aureus, C. jejuni, A. butzleri, and L. monocytogenes in raw poultry meat samples. Ninety-four raw ostrich, turkey, chicken, and quail meat samples were collected and subjected to culture-based analysis. Staphylococcus aureus, C. jejuni, A. butzleri, and L. monocytogenes isolates were confirmed by standard biochemical techniques. The occurrence of A. butzleri, C. jejuni, L. monocytogenes, and S. aureus in poultry meat samples was 11.45%, 17.70%, 1.04%, and 16.66%, respectively. L. monocytogenes was absent in chicken, turkey, and ostrich meat samples. Only one quail meat (4.16%) was positive for L. monocytogenes. The uppermost contamination rate with A. butzleri, C. jejuni, and S. aureus was found in chicken (25%), turkey (25%), and turkey (25%) meat samples, respectively. The concurrent occurrence of A. butzleri + C. jejuni + S. aureus bacteria amid the examined poultry meat samples was 2.08%. This is an initial report of A. butzleri, S. aureus, C. jejuni, and L. monocytogenes in poultry meat samples. Adequate cooking of poultry meat can diminish foodborne diseases due to A. butzleri, S. aureus, L. monocytogenes, and C. jejuni bacteria, and these species may constitute a public health problem.


The role of substance P-containing fibers in sympathetic ganglia: effect of capsaicin.
Capsaicin was given subcutaneously to guinea pigs and the effect on substance P-immunoreactive (SP-I) fibers in the celiac/superior mesenteric and inferior mesenteric ganglia was observed at 2 day and 8-10 day intervals. Capsaicin (125 mg) treatment led to almost total disappearance of SP-I fibers from all areas examined in both short- and long-term animals. This effect applied equally to the dense network of varicose SP-I fibers and to basket-like SP-I contacts with principal ganglionic neurons. The effect of capsaicin on SP-I fibers in the mesenteric ganglia provides a strong indication that these fibers represent a homogeneous population of visceral sensory afferents. This is supported by other lines of anatomical evidence in the literature. Taken together with studies that have shown axodendritic contact of SP-I terminals on principal ganglionic neurons and neuro-modulatory effects of SP on these neurons, it may be hypothesized that SP-I fibers in the mesenteric ganglia represent collaterals of visceral sensory afferents forming a subspinal feedback arc.


Effect of histamine methylation inhibitors on entry of 14C-histamine into brain.
Pretreatment of mice, rats and guinea pigs with inhibitors of histamine methylation, followed by systemic injection of 14C-histamine, results in a significant increase in brain 14C-histamine relative to controls. It is suggested that the histamine methylating enzyme participates in the blood-brain barrier to histamine.


Positron annihilation signatures associated with the outburst of the microquasar V404 Cygni.
Microquasars are stellar-mass black holes accreting matter from a companion star and ejecting plasma jets at almost the speed of light. They are analogues of quasars that contain supermassive black holes of 10(6) to 10(10) solar masses. Accretion in microquasars varies on much shorter timescales than in quasars and occasionally produces exceptionally bright X-ray flares. How the flares are produced is unclear, as is the mechanism for launching the relativistic jets and their composition. An emission line near 511 kiloelectronvolts has long been sought in the emission spectrum of microquasars as evidence for the expected electron-positron plasma. Transient high-energy spectral features have been reported in two objects, but their positron interpretation remains contentious. Here we report observations of γ-ray emission from the microquasar V404 Cygni during a recent period of strong flaring activity. The emission spectrum around 511 kiloelectronvolts shows clear signatures of variable positron annihilation, which implies a high rate of positron production. This supports the earlier conjecture that microquasars may be the main sources of the electron-positron plasma responsible for the bright diffuse emission of annihilation γ-rays in the bulge region of our Galaxy. Additionally, microquasars could be the origin of the observed megaelectronvolt continuum excess in the inner Galaxy.


Bone setting for prolonged neck pain: a randomized clinical trial.
To study the natural history of prolonged neck pain and the effectiveness of bone setting as its treatment. A randomized clinical trial with blinded outcome assessment and 1-year follow-up was completed. Forty-two working-aged patients with nonspecific neck pain for at least 1 month and no contraindications to manipulative therapies were recruited. They were randomly allocated into 5 weekly sessions of bone setting provided by 2 experienced folk healers (22 patients) or follow-up without therapy (20 patients). The primary outcomes were neck mobility after the 5-week therapy period and the Million scales modified for neck pain at 5 weeks, and 3, 6, and 12 months after baseline. Secondary outcomes included self-rated improvement and pain drawing at 5 weeks, and 3, 6, and 12 months after baseline, Beck depression scales at 5 weeks and 12 months after baseline, and sick leaves, additional therapies, and pain medication during 1 year after baseline. At baseline, neck pain was reported constant or increasing by 51% and episodic by 49% of the patients with mean duration of symptoms of 4.3 years for the bone setting and 8.4 years for the control group. Seventy-eight percent of the patients participated in the clinical measurements at 5 weeks, and 90% returned the questionnaires after 1 year. The cervical mobility of the bone setting patients increased 29% in the frontal, 23% in the sagittal, and 16% in the horizontal plane, whereas the figures for the control group were -1.4%, 1.0%, and 3.0%, respectively. The mean Million index of the bone setting group (50.6 mm at baseline) was 18.5 mm at 5 weeks, 21.2 mm at 3 months, 22.9 mm at 6 months, and 14.2 mm at 1 year. The figures for the control group were 53.2 mm at baseline, and 4.0, 6.2, 5.4, and 5.5 mm at the corresponding follow-up points. After 1 year, improvement was reported by 80% of the bone setting and 28% of the control patients. In this study, manual therapy had a measurable effect on the mobility of cervical spine at 5 weeks and an effect on pain that lasted for at least half a year.


[µ-opioid receptors in the central nucleus of the amygdala modulate sucrose solution intake in rats].
To explore the role of µ-opioid receptors (MOR) in the central nucleus of the amygdala (CeA) in modulating sucrose solution intake in rats. Sprague-Dawley rats received intra-CeA injection of MOR agonist DAMGO or saline, and then underwent two bottle choice test between sucrose solution and distilled water. After intake of sucrose solution or distilled water, activated neurons in the CeA were labeled and identified with MOR/Fos-double labeling immunohistochemistry. Compared with saline injection, intra-CeA injection of DAMGO significantly increased sucrose solution intake in rats over a 3-h period. Sucrose solution intake induced significantly more c-Fos and MOR/Fos double-labeled neurons in the CeA than distilled water intake. The CeA participates in modulation of sucrose intake in rats, and MOR may partly mediate this mechanism.


Functional interplay between p53 acetylation and H1.2 phosphorylation in p53-regulated transcription.
Linker histone H1.2 has been shown to suppress p53-dependent transcription through the modulation of chromatin remodeling; however, little is known about the mechanisms governing the antagonistic effects of H1.2 in DNA damage response. Here, we show that the repressive action of H1.2 on p53 function is negatively regulated via acetylation of p53 C-terminal regulatory domain and phosphorylation of H1.2 C-terminal tail. p53 acetylation by p300 impairs the interaction of p53 with H1.2 and triggers a rapid activation of p53-dependent transcription. Similarly, DNA-PK-mediated phosphorylation of H1.2 at T146 enhances p53 transcriptional activity by impeding H1.2 binding to p53 and thereby attenuating its suppressive effects on p53 transactivation. Consistent with these findings, point mutations mimicking modification states of H1.2 and p53 lead to a significant increase in p53-induced apoptosis. These data suggest that p53 acetylation-H1.2 phosphorylation cascade serves as a unique mechanism for triggering p53-dependent DNA damage response pathways.


Assessment of new onset postcoronary artery bypass surgery atrial fibrillation: current practice pattern review and the development of treatment guidelines.
The incidence of postcoronary artery bypass graft (CABG) atrial fibrillation (AF) is 22.5% at the QEII Health Sciences Centre and the mean length of stay is 5.5 days greater than for those patients who do not experience this complication. Appropriate pharmacological management is important to prevent the potential morbidity from AF, such as thromboembolism, congestive heart failure, cardiogenic shock and coronary ischemia. This project compared current practice patterns in the management of post-CABG AF with local practice pattern beliefs and evidence from the primary literature. Subsequently, treatment guidelines were designed to help guide a rationale treatment approach. To promote appropriate treatment strategies for post-CABG AF and increase local practitioner awareness of drug-use outcomes by developing consensus treatment guidelines. There were three phases. In phase 1, a retrospective chart analysis of 35 post-CABG AF patients over three consecutive months was conducted to assess current practice patterns. All published studies on this subject were also collected and analysed. A survey of pharmacological treatment preferences was distributed to local stakeholders during phase 2. The third phase involved the development and implementation of treatment guidelines. This study identified a highly variable approach to the treatment of post-CABG AF. The mean number of agents used to treat AF post-CABG was two (range 1-4); all patients (100%) were prescribed rate-controlling agents and 37% were prescribed an antiarrhythmic drug. There was also a mismatch between practice pattern beliefs and actual practice. This reinforced the need for a consistent treatment approach that was facilitated with the development and implementation of local guidelines.


Suppression of Malachite Green-Induced Toxicity to Human Liver Cells Utilizing Host-Guest Chemistry of Cucurbit[7]uril.
We investigated a host-guest complex between cucurbit[7]uril and malachite green, and its effect on the toxicity to human liver cells. The host-guest complexation was evaluated by a UV/vis titration and electrospray-ionization mass spectrometry. Interestingly, the host-guest complex resulted in remarkable suppression of the toxicity of malachite green in its practical concentration range (ca. ∼6 μM). This study is one step forward to the active control of the biological effects of potent toxicants utilizing host-guest chemistry.


The method for on-site determination of trace concentrations of methyl mercaptan and dimethyl sulfide in air using a mobile mass spectrometer with atmospheric pressure chemical ionization, combined with a fast enrichment/separation system.
A method for fast simultaneous on-site determination of methyl mercaptan and dimethyl sulfide in air was developed. The target compounds were actively collected on silica gel, followed by direct flash thermal desorption, fast separation on a short chromatographic column and detection by means of mass spectrometer with atmospheric pressure chemical ionization. During the sampling of ambient air, water vapor was removed with a Nafion selective membrane. A compact mass spectrometer prototype, which was designed earlier at Trofimuk Institute of Petroleum Geology and Geophysics, was used. The minimization of gas load of the atmospheric pressure ion source allowed reducing the power requirements and size of the vacuum system and increasing its ruggedness. The measurement cycle is about 3 min. Detection limits in a 0.6 L sample are 1 ppb for methyl mercaptan and 0.2 ppb for dimethyl sulfide.


Outcomes of a randomised controlled trial of a complex genetic counselling intervention to improve family communication.
When an inherited genetic condition is diagnosed in an individual it has implications for other family members. Privacy legislation and ethical considerations can restrict health professionals from communicating directly with other family members, and so it is frequently the responsibility of the first person in a family to receive the diagnosis (the proband) to share this news. Communication of genetic information is challenging and many at-risk family members remain unaware of important information that may be relevant to their or their children's health. We conducted a randomised controlled trial in six public hospitals to assess whether a specifically designed telephone counselling intervention improved family communication about a new genetic diagnosis. Ninety-five probands/parents of probands were recruited from genetics clinics and randomised to the intervention or control group. The primary outcome measure was the difference between the proportion of at-risk relatives who contacted genetics services for information and/or genetic testing. Audit of the family genetic file after 18 months revealed that 25.6% of intervention group relatives compared with 20.9% of control group relatives made contact with genetic services (adjusted odds ratio (OR) 1.30, 95% confidence interval 0.70-2.42, P=0.40). Although no major difference was detected overall between the intervention and control groups, there was more contact in the intervention group where the genetic condition conferred a high risk to offspring (adjusted OR 24.0, 95% confidence interval 3.4-168.5, P=0.001). The increasing sophistication and scope of genetic testing makes it imperative for health professionals to consider additional ways of supporting families in communicating genetic information.


A newly designed method for removal of the pineal body, and depression of convulsions and enhancement of exploratory movements by pinealectomy in mice.
We designed a simple technique for surgical excision of the pineal body in mice. Such can be accomplished in 10 min by a skilled worker and there are no lesions whatever. In pinealectomized El-strain mice the appearance of convulsions was inhibited up to 30 days, while intact El-mice were all fallen into convulsions by being shaken up and down on a flat carton. Pentazole-induced convulsions propagate from one dd-mouse to another in an aggregated state, but such propagation did not occur in pinealectomized animals. Exploratory movements of pinealectomized dd-mice increased as compared to intact animals and the increase was always more extensively observed in El-mice in which, even in the intact animals, the exploratory movements were much more than those of dd-mice. From the above-mentioned experiment, it is considered that the pineal body plays a role not only in initiating but also in propagating convulsions, and that it may have a depressive action on motor activities in mice.


Epidemiology of esophageal cancer in Yanting - regional report of a national screening programme in China.
Yanting in Sichuan Province is one of the highest risk areas of esophageal cancer (EC) in the world. We here summarize the epidemiology of EC in Yanting using data from the national screening programme during 2006-2011. Random cluster sampling was used to select a proportion of natural villages from six towns in Yanting, and residents aged 40-69 years old were invited for screening. Participants were screened using endoscopy with iodine staining and then confirmed by histological examinations. The overall detection rates of low-grade hyperplasia (LH), moderate hyperplasia (MH), high-grade hyperplasia (HH), carcinoma in situ (CIS), intramucosal carcinoma (IC) and invasive carcinoma (INC) were 5.33%, 1.28%, 0.68% , 0.15% , 0.06% and 0.29%, respectively. The detection rates of LH, MH, HH and INC increased with age, reaching the peak among those aged 60-65 years, and the prevalences of LH and MH were higher among men than among women. In addition, the detection rates of hyperplasia were much higher in mountainous than in hilly areas. Among the high risk population, there are a great number of people with early-stage EC or precancerous conditions who do not have presenting symptoms. In particular, the elderly, men, or those living in mountainous areas are the most vulnerable population. It is therefore important to reinforce health education and screening services among such high risk populations.


Delayed expansion and contraction of CD8+ T cell response during infection with virulent Salmonella typhimurium.
Ag presentation to CD8(+) T cells often commences immediately after infection, which facilitates their rapid expansion and control of infection. Subsequently, the primed cells undergo rapid contraction. We report that this paradigm is not followed during infection with virulent Salmonella enterica, serovar Typhimurium (ST), an intracellular bacterium that replicates within phagosomes of infected cells. Although susceptible mice die rapidly (approximately 7 days), resistant mice (129 x 1SvJ) harbor a chronic infection lasting approximately 60-90 days. Using rOVA-expressing ST (ST-OVA), we show that T cell priming is considerably delayed in the resistant mice. CD8(+) T cells that are induced during ST-OVA infection undergo delayed expansion, which peaks around day 21, and is followed by protracted contraction. Initially, ST-OVA induces a small population of cycling central phenotype (CD62L(high)IL-7Ralpha(high)CD44(high)) CD8(+) T cells. However, by day 14-21, majority of the primed CD8(+) T cells display an effector phenotype (CD62L(low)IL-7Ralpha(low)CD44(high)). Subsequently, a progressive increase in the numbers of effector memory phenotype cells (CD62L(low)IL-7Ralpha(high)CD44(high)) occurs. This differentiation program remained unchanged after accelerated removal of the pathogen with antibiotics, as majority of the primed cells displayed an effector memory phenotype even at 6 mo postinfection. Despite the chronic infection, CD8(+) T cells induced by ST-OVA were functional as they exhibited killing ability and cytokine production. Importantly, even memory CD8(+) T cells failed to undergo rapid expansion in response to ST-OVA infection, suggesting a delay in T cell priming during infection with virulent ST-OVA. Thus, phagosomal lifestyle may allow escape from host CD8(+) T cell recognition, conferring a survival advantage to the pathogen.


Heparin therapy for recent transient focal cerebral ischemia.
The Mayo Clinic medical records and records linkage system were used to identify stroke-free residents of Rochester, Minnesota, who were examined within 30 days after the first transient cerebral ischemic attack (TIA) during the period 1955 through 1979. The patients were divided into two groups: those given heparin within 30 days after the first attack and those not given heparin. Death, stroke, and either stroke or TIA were separate endpoints in Kaplan-Meier analyses of data from the day of initial examination through the 30th day thereafter. The probabilities of survival, survival free from stroke, and survival free from TIA for the heparin-treated group were not significantly different from those probabilities for the comparison group. The rate of hemorrhagic complications was 3.2 per 100 person-days of heparin therapy. Retroperitoneal hemorrhage, the most serious complication, was the cause of one death and one case of femoral neuropathy.


Method for characterizing viscoelasticity of human gluteal tissue.
Characterizing compressive transient large deformation properties of biological tissue is becoming increasingly important in impact biomechanics and rehabilitation engineering, which includes devices interfacing with the human body and virtual surgical guidance simulation. Individual mechanical in vivo behaviour, specifically of human gluteal adipose and passive skeletal muscle tissue compressed with finite strain, has, however, been sparsely characterised. Employing a combined experimental and numerical approach, a method is presented to investigate the time-dependent properties of in vivo gluteal adipose and passive skeletal muscle tissue. Specifically, displacement-controlled ramp-and-hold indentation relaxation tests were performed and documented with magnetic resonance imaging. A time domain quasi-linear viscoelasticity (QLV) formulation with Prony series valid for finite strains was used in conjunction with a hyperelastic model formulation for soft tissue constitutive model parameter identification and calibration of the relaxation test data. A finite element model of the indentation region was employed. Strong non-linear elastic but linear viscoelastic tissue material behaviour at finite strains was apparent for both adipose and passive skeletal muscle mechanical properties with orthogonal skin and transversal muscle fibre loading. Using a force-equilibrium assumption, the employed material model was well suited to fit the experimental data and derive viscoelastic model parameters by inverse finite element parameter estimation. An individual characterisation of in vivo gluteal adipose and muscle tissue could thus be established. Initial shear moduli were calculated from the long-term parameters for human gluteal skin/fat: G(∞,S/F)=1850 Pa and for cross-fibre gluteal muscle tissue: G(∞,M)=881 Pa. Instantaneous shear moduli were found at the employed ramp speed: G(0,S/F)=1920 Pa and G(0,M)=1032 Pa.


Clinical characteristics of mutation carriers in a large family with glucokinase diabetes (MODY2).
To investigate the prevalence and clinical characteristics of heterozygotes of the glucokinase gene mutations G264S and IVS8+2 in the extended pedigree of two patients with permanent neonatal diabetes as a result of glucokinase deficiency (IVS8+2 homozygosity and IVS8+2/G264S compound heterozygosity). Eighty-eight first, second and third degree family members of the two patients with permanent neonatal diabetes were genotyped. Clinical, laboratory and historical data were collected via chart reviews. Thirty-one IVS8+2 and three G264S heterozygotes were identified. Of these, 18/34 (52.9%) had diabetes and 9/34 (26.5%) impaired fasting glucose (IFG), compared with 1/54 (1.9%) with diabetes and 2/54 (3.7%) with IFG in the non-carrier group. Odds ratio for heterozygotes was 70.4 (95% CI 16.9-293.5 and P < 0.001). Mean body mass index of heterozygotes (> 18 years of age) who had diabetes was 27.1 +/- 2.66, compared with 23.18 +/- 4.72 for heterozygotes with normal glucose levels (P < 0.05). While none of the non-carrier women had gestational diabetes, eight of the 10 heterozygotes developed gestational diabetes. Inheritance of a glucokinase mutation by the fetus from a carrier mother resulted in a significant reduction in birthweight (3600 +/- 570 vs. 2970 +/- 390 grams, P < 0.05). These data support the association between carriage of GCK gene mutations, G264S and IVS8+2, and the development of diabetes, impaired fasting glucose and reduced birthweight. Moreover, in heterozygotes, a clear correlation between body mass index and the development of diabetes was observed. These findings underline the need for surveillance and prevention in individuals at risk.


Persistence of tolerance to a single dose of ethanol in the selectively-bred alcohol-preferring P rat.
The persistence of tolerance to a single dose of ethanol was examined in the selectively-bred alcohol-preferring P line of rats. Tolerance was measured by a test that required trained rats to jump onto a descending platform to avoid footshock. On day 0, each trained rat received a single IP injection of 2.5 g ethanol/kg body weight and was tested every 15 minutes for recovery to a criterion of 75% of pre-alcohol training performance. The second ethanol injection of 2.5 g/kg and testing were carried out seven days later for one group (n = 12), and 14 days later for another group (n = 12). Tolerance was assessed by the differences in time required to recover to criterion performance and blood alcohol concentrations (BACs) at time of recovery on day 0 vs. day 7 and day 14. The mean recovery times and BACs on day 0 were 156 +/- 5 minutes and 222 +/- 6 mg%, respectively. The group injected on day 7 exhibited shorter recovery times of 113 +/- 4 minutes and higher BACs at recovery of 261 +/- 4 mg%, while the group injected on day 14 did not show any significant differences from the values obtained on day 0. In a second experiment, the persistence of tolerance in P rats was compared with that of rats from the alcohol-nonpreferring NP line and of stock Wistar rats (n = 6/group). All rats were trained and tested for recovery to criterion after 2.5 g ethanol/kg on day 0 as described for the first experiment. The rats were then injected with ethanol and tested for tolerance on three subsequent occasions.(ABSTRACT TRUNCATED AT 250 WORDS)


Papers don't write themselves: Creating a system to support writing productivity.
To be a successful academic writer, we need a strong awareness of the circumstances that support our writing productivity. First and foremost, writing requires time-on-task. To obtain focused, effective writing time, we may need to increase our accountability related to writing. In addition, each writer needs a writing system - a set of processes that helps them to reliably complete their writing work. To build an effective writing system, we advocate for observation, reflection, and experimentation related to our writing processes. In particular, examination of the what, where, when, and how of writing is critical. Strategies for optimizing productivity during writing sessions are also needed. Strengthening writing productivity requires mechanisms for accountability, awareness of our writing process, and strategies to enhance the effectiveness of each writing session.


Augmented production of soluble CD93 in patients with systemic sclerosis and clinical association with severity of skin sclerosis.
The cell surface protein CD93, expressed on endothelial and myeloid cells, mediates phagocytosis, inflammation and cell adhesion. A soluble form of CD93 (sCD93) is released during inflammation. To determine the serum sCD93 level and its association with clinical parameters in patients with systemic sclerosis (SSc). Serum sCD93 levels were examined by enzyme-linked immunosorbent assay in 59 patients with SSc, 24 patients with systemic lupus erythematosus and 47 healthy individuals. The expression of CD93 in skin tissues was examined immunohistochemically. In a retrospective longitudinal study, sera from 11 patients with SSc were analysed. Serum sCD93 levels were increased in patients with SSc compared with healthy individuals (P<0·001). Patients with diffuse cutaneous SSc showed greater levels of sCD93 than those with limited cutaneous SSc (P<0·01) or systemic lupus erythematosus (P<0·01). Serum sCD93 levels correlated positively with the severity of skin sclerosis. Strong CD93 immunostaining was observed on endothelial cells in lesional skin tissues. In the longitudinal study, sCD93 levels decreased in parallel with improvement in skin sclerosis. Serum sCD93 levels are increased in patients with SSc and correlate with the severity and activity of skin sclerosis. CD93 may contribute to the development of skin fibrosis in SSc.


Rat brain capillary thrombomodulin: structure and function.
The anticoagulant transmembrane glycoprotein thrombomodulin (TM) is expressed at the luminal surface of vascular endothelial cells. Recently, we showed that TM antigen and TM mRNA are expressed in brain microvessels in several species and that brain capillaries have the capability to activate protein C. The activation of protein C in brain microcirculation was greatly impaired by major stroke risk factors in rats due to downregulation of TM. In this study, a partial sequence of TM was determined from TM mRNA from brain capillaries examined in brain capillaries of the rat, a species that provides a useful model to investigate stroke mechanisms in relation to brain hemostasis. The predicted deduced amino acid sequences for rat TM were compared with other TM sequences. Particularly high homology (77-100%) among functional domains of the protein, i.e., the epidermal growth factor repeats (EGFRs) 1-6 and the transmembrane region, was observed between mice and rats. Somewhat less degree of homology was observed for bovine and human EGFRs 1-6, while the homology of the transmembrane region was 92-96%. All cysteine residues were conserved among the TM sequences, and specific amino acids previously suggested to be essential for activation of protein C by thrombin TM were highly conserved. We conclude that the highly conserved mRNA and protein sequences may reflect a similar anticoagulant role of TM in brain endothelial and systemic vascular endothelial cells across different species.


Development of thermostable dextranase from Streptococcus mutans (SmdexTM) through in silico design employing B-factor and Cartesian-ΔΔG.
The thermal stability of enzymes dramatically limits their application in the industrial field. Based on the crystal structure, we conducted a semi-rational design according to the B-factor and free energy values to improve the stability of dextranase from Streptococcus mutans (SmdexTM). The B-factor values of Asn102, Asn503, Asp501 and Asp500 were the highest predicted by B-FITTER. Then Rosetta was used to simulate the saturation mutations of Asn102, Asn503, Asp501 and Asp500. The mutated amino acid was designed according to the change of acG. The results showed that the thermal stability of N102P, N102C, D500G, and D500T was improved, and the half-lives of N102P/D500G and N102P/D500T at 45 °C were increased to 3.14 times and 2.44 times, respectively. Analyzing the interaction of amino acids by using Discovery Studio 4.5, it was observed that the thermal stability of dextranase was improved due to the increase in hydrophobicity and the number of hydrogen bonds of the mutant enzyme. The catalytic efficiency of N102P/D500T was increased. Compared with the hydrolyzed products of SmdexTM, the mutant enzymes do not change the specificity of hydrolysates.


[Treatment strategies for gastroesophageal reflux disease].
Gastroesophageal reflux disease (GERD) is a very common disorder. Therapeutic options include lifestyle modifications, medical therapy, laparoscopic antireflux surgery, and three more recent options-injection therapy to the lower esophageal sphincter, endoscopic sewing procedures, and radio frequency ablation therapy. Medical therapy is effective in most patients but not always successful with advanced disease. Up to 70% of subjects do not have adequate nocturnal control of gastric acid secretion with 20 mg of omeprazole given twice per day. Patients who do not tolerate medical therapy, who respond inadequately, or who want to avoid life-long drug therapy are candidates for alternate treatments. Studies on endoscopic procedures such as polymethylmethacrylate (PMMA) injection, the Stretta procedure,and endoscopic suturing techniques all suffer from having small study groups for each procedure,unknown durability, short follow-up, and the absence of randomized, controlled procedures. Limitations on endoscopic techniques are esophageal motility disorders, severe esophagitis, and larger hiatal hernias. Laparoscopic antireflux surgery remains a well-established, durable alternative to long-term medical therapy. It has the benefits of convenience, safety, minimal complications, improved quality of life, and low cost. Alternative methods will have to earn their place against this gold standard.


(11)C-Choline PET/CT for restaging prostate cancer. Results from 4,426 scans in a single-centre patient series.
To evaluate (11)C-choline PET/CT as a diagnostic tool for restaging prostate cancer (PCa), in a large, homogeneous and clinically relevant population of patients with biochemical recurrence (BCR) of PCa after primary therapy. The secondary aim was to assess the best timing for performing (11)C-choline PET/CT during BCR. We retrospectively analysed 9,632 (11)C-choline PET/CT scans performed in our institution for restaging PCa from January 2007 to June 2015. The inclusion criteria were: (1) proven PCa radically treated with radical prostatectomy (RP) or with primary external beam radiotherapy (EBRT); (2) PSA serum values available; (3) proven BCR (PSA >0.2 ng/mL after RP or PSA >2 ng/mL above the nadir after primary EBRT with rising PSA levels). Finally, 3,203 patients with recurrent PCa matching all the inclusion criteria were retrospectively enrolled and 4,426 scans were analysed. Overall, 52.8 % of the (11)C-choline PET/CT scans (2,337/4,426) and 54.8 % of the patients (1,755/3,203) were positive. In 29.4 % of the scans, at least one distant finding was observed. The mean and median PSA values were, respectively, 4.9 and 2.1 ng/mL at the time of the scan (range 0.2 - 50 ng/mL). In our series, 995 scans were performed in patients with PSA levels between 1 and 2 ng/mL. In this subpopulation the positivity rate in the 995 scans was 44.7 %, with an incidence of distant findings of 19.2 % and an incidence of oligometastatic disease (one to three lesions) of 37.7 %. The absolute PSA value at the time of the scan and ongoing androgen deprivation therapy were associated with an increased probability of a positive (11)C-choline PET/CT scan (p < 0.0001). In the ROC analysis, a PSA value of 1.16 ng/mL was the optimal cut-off value. In patients with a PSA value <1.16 ng/mL, 26.8 % of 1,426 (11)C-choline PET/CT scans were positive, with oligometastatic disease in 84.7 % of positive scans. In a large cohort of patients, the feasibility of (11)C-choline PET/CT for detecting the sites of metastatic disease in PCa patients with BCR was confirmed. The PSA level was the main predictor of a positive scan with 1.16 ng/mL as the optimal cut-off value. In the majority of positive scans oligometastatic disease, potentially treatable with salvage therapies, was observed.


The veno-occlusive mechanism of the canine corpus cavernosum: angiographic and pharmacologic studies.
Studies were designed to document the normal angiography and pressure-volume characteristics of the canine corpus cavernosum, evaluate the effects of various vasoactive agents, and characterize a veno-occlusive mechanism. In fourteen dogs, baseline cavernosography demonstrated venous drainage via six to ten tributaries arising from the crura and entering the deep penile veins. Control cavernosometry during infusion of saline at 0.33 ml./sec. led to a rise in intracavernosal pressure (ICP) from 24.9 +/- 7.9 mm. Hg to 68.4 +/- 21.1 mm. Hg. Intracavernosal injection of a number of vasodilators, including papaverine, nitroglycerin, acetylcholine, and prostaglandin E2, raised baseline ICP significantly, caused extreme elevation of pressure during saline infusion (greater than 450 mm. Hg), and narrowed or obliterated the venous lumena at the site of tunica perforation, as judged angiographically. These effects could be reversed with phenoxybenzamine or norepinephrine. Our results further support the current understanding of the canine veno-occlusive mechanism.


Quantifying the uncertainty of internal variability in future projections of seasonal soil moisture droughts over China.
Understanding and quantifying drought projection uncertainty at regional scales is critical for climate adaptations and mitigations. The model uncertainty has been well represented by multi-model ensemble through the implementation of Coupled Model Intercomparison Projects (CMIPs). However, the uncertainty from internal variability is usually quantified by statistical fitting due to insufficient initial-condition ensembles for each global climate model (GCM), resulted in an underestimation of the uncertainty. In this study, Single Model Initial-condition Large Ensembles (SMILEs) that represent internal variability based on GCMs with different initial conditions, are combined with CMIP5 and CMIP6 GCMs to separate the uncertainty of seasonal soil drought projection over China. All three datasets show that internal variability dominates uncertainty for the near-term drought projection, and the internal variability uncertainty is exceeded by model uncertainty for the long-term projection. By using SMILEs as a benchmark, we revisit the method from Hawkins and Sutton (2009; hereafter, HS09) and find that this method performs well for drought projection at national scale over China. For drought projections at regional scale, however, HS09 method underestimates the uncertainty of internal variability for drought frequency, duration and intensity by 27%-54%, 15%-47% and 16%-31%, respectively. Our study highlights the importance of the selected approach for addressing the internal variability in the near-term projection of regional extremes and related adaptations.


Persistent myalgia following whiplash.
Persistent myalgia following whiplash is commonly considered the result of poor psychosocial status, illness behavior, or failing coping skills. However, there is much evidence that persistent myalgia may be due to neurophysiologic mechanisms involving peripheral and central sensitization. Myofascial trigger points may play a crucial role in maintaining sensitization. Recent research suggests that the chemical environment of myofascial trigger points is an important factor. Several consequences are reviewed when central pain mechanisms and myofascial trigger points are included in the differential diagnosis and in the management of patients with persistent pain following whiplash.


The GLCCI1 rs37973 variant and the efficacy of inhaled corticosteroids in the treatment of asthma: A meta-analysis.
This study investigated the relationship between the glucocorticoid-induced transcript 1 (GLCCI1) gene variant and the degree of improvement in lung function with inhaled corticosteroids (ICS). We searched the PubMed, Embase, Cochrane Library, CBM, CNKI and Wanfang databases to obtain studies on the GLCCI1 rs37973 variant and the efficacy of ICS in asthma. The overall meta-analysis showed that patients with the GG phenotype (mutant homozygotes) exhibited significantly smaller forced expiratory volume in 1 sec (FEV1) change than patients with the AG phenotype (mutant heterozygous) (MD = -0.08, 95% CI [-0.12, -0.03], P = 0.001). Compared with the AA phenotype (wild homozygotes), the GG phenotype (MD = -4.23, 95% CI [-6.09, -2.38], P < 0.00001) and AG phenotype (MD = -1.92, 95% CI [-2.35, -1.49], P < 0.00001) had significantly smaller FEV1%pred changes. The FEV1 change subgroup analysis showed that the GG phenotype group was smaller than the AA phenotype group at 8 (MD = -0.53, 95% CI [-0.91, -0.14], P = 0.007), 12 (MD = -0.16, 95% CI [-0.30, -0.02], P = 0.02) and 24 (MD = -0.09, 95% CI [-0.17, -0.01], P = 0.02) weeks of treatment; the GG phenotype group was smaller than the AG phenotype group at 12 weeks (MD = -0.08, 95% CI [-0.15, -0.01], P = 0.02). This meta-analysis suggests that the GLCCI1 rs37973 variant affects the efficacy of ICS and that the presence of the G allele attenuates the improvement in lung function with ICS.


Association of polymorphisms in the erythropoietin gene with diabetic retinopathy: a case-control study and systematic review with meta-analysis.
Diabetic retinopathy (DR) is characterized by ischemia, hypoxia, and angiogenesis. Erythropoietin (EPO), an angiogenic hormone, is upregulated in DR, and the association of EPO genetic variants with DR is still uncertain, as conflicting results have been reported. Therefore, we performed a case-control study followed by a meta-analysis to investigate whether the rs1617640, rs507392, and rs551238 polymorphisms in EPO gene are associated with DR. The case-control study included 1042 Southern Brazilians with type 2 diabetes (488 without DR and 554 with DR). Eligible studies for the meta-analysis were searched from electronic databases up to June 1, 2021. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for five genetic inheritance models. The minor alleles of the EPO polymorphisms had nearly the same frequency in all groups of patients (35%), and no association was detected with DR in the case-control study. The meta-analysis included 14 independent sets of cases and controls with 9117 subjects for the rs1617640 polymorphism and nine independent sets with more than 5000 subjects for the rs507392 and rs551238 polymorphisms. The G allele of the rs1617640 polymorphism was suggestively associated with DR under the dominant (OR = 0.82, 95% CI: 0.68-0.98), heterozygous additive (OR = 0.82, 95% CI: 0.69-0.97), and overdominant (OR = 0.88, 95% CI: 0.79-0.97) models. In the subgroup analyses, the G allele was also suggestively associated with proliferative DR (PDR), non-proliferative DR (NPDR), and DR (PDR + NPDR) among patients with type 1 diabetes (T1DM) or non-Asian ancestry. After considering the Bonferroni correction for multiple comparisons, the G allele remained associated with NPDR and DR in T1DM. Regarding the rs507392 and rs551238 polymorphisms, no association was found between these variants and DR. Our findings provide additional support to EPO as a susceptibility gene for DR, with the rs1617640 polymorphism deserving further investigation.


An optimal medicinal and edible Chinese herbal formula attenuates particulate matter-induced lung injury through its anti-oxidative, anti-inflammatory and anti-apoptosis activities.
Identifying novel strategies to prevent particulate matter (PM)-induced lung injury is crucial for the reduction of the morbidity of chronic respiratory diseases. The combined intervention represented by herbal formulae for simultaneously targeting multiple pathological processes can provide a more beneficial effect than the single intervention. The aim of this paper is therefore to design a safe and effective medicinal and edible Chinese herbs (MECHs) formula against PM-induced lung injury. PM-induced oxidative stress, inflammatory response and apoptosis A549 cell model were used to screen anti-oxidant, anti-inflammatory and anti-apoptotic MECHs, respectively. A network pharmacology method was utilized to rationally design a novel herbal formula. Ultra performance liquid chromatography-mass spectrometer was utilized to assess the quality control of MECHs formula. The excretion of magnetic iron oxide nanospheres of the MECHs formula was estimated in zebrafish. The MECH formula against PM-induced lung injury was investigated with mice experiments. Five selected herbs were rationally designed to form a new MECH formula, including Citri Exocarpium Rubrum (Juhong), Lablab Semen Album (Baibiandou), Atractylodis Macrocephalae Rhizoma (Baizhu), Mori Folium (Sangye) and Polygonati Odorati Rhizoma (Yuzhu). The formula effectively promoted the magnetic iron oxide nanospheres excretion in zebrafish. The mid/high dose formula significantly prevented PM-induced lung damage in mice by enhancing the activity of SOD and GSH-Px, reducing the MDA and ROS level and attenuating the upregulation of pro-inflammatory cytokine (IL-6, IL-8, IL-1β and TNF-α), down regulating the protein expression of NF-κB, STAT3 and Caspase-3. Our findings suggest that the effective MECHs formula will become a novel strategy for preventing PM-induced lung injury and provide a paradigm for the development of functional foods using MECHs.


Nonaromatizable androgens may stimulate a male mouse reproductive behavior by binding estrogen receptors.
Castrated DBA/2J male mice emitted 70 kHz vocalizations to female stimuli in response to 10 days of treatment with either testosterone (T, 300 micrograms/day), diethylstilbestrol (DES, 1 or 3 micrograms/day) or methyltrienolone (R1881, 900 micrograms/day). Lower dosages of R1881 (300 and 600 micrograms/day) and the oil vehicle were relatively ineffective in restoring vocalizations. The effects of these hormones on restoring seminal vesicle weight did not always parallel their effects upon behavior. In general T and R1881 (600 and 900 micrograms/day) were effective in restoring seminal vesicles while DES, the lowest dose of R1881 (300 micrograms/day), and the oil vehicle were ineffective. In receptor competition studies, R1881 pretreatment significantly reduced estrogen binding in hypothalamic-preoptic cytosol. In fact the most effective dose for restoring vocalizations (900 micrograms/day) reduced available estrogen binding sites by 91%. We propose that the male-typical vocalizations of mice may normally be stimulated through the activation of estrogen receptors following androgen aromatization and that the ability of a pharmacological dosage of R1881 (900 micrograms/day) to restore behavior may be due to interaction with estrogen receptors in the brain.


Agonist enhacement of macrocyclic lactone activity at a glutamate-gated chloride channel subunit from Haemonchus contortus.
The mode of action of ivermectin (IVM) in nematodes appears to be the opening of inhibitory ion channels, including the glutamate-gated chloride channel (GluCl). Recently, it has been shown that IVM binds with high affinity to a Haemonchus contortus GluCl subunit (HcGluCla) expressed in COS-7 cells, and this binding is potentiated in the presence of glutamate. To gain further insight into the potentiation of macrocyclic lactone anthlemintics we have screened various glutamatergic and nonglutamatergic ligands for their ability to enhance [ 3H ] IVM binding to HcGluCla. Of the ligands tested, only glutamate and ibotenate potentiated [ 3H ] IVM binding. Interestingly, these ligands have also been shown to open the HcGluCla channel expressed in Xenopus oocytes. We examined the effect of ibotenate on macrocyclic lactone binding in more detail and found that it caused a 7-fold enhancement in [ 3H ] IVM binding affinity and a 4-fold increase in [ 3H ] MOX binding affinity. In in vivo efficacy studies, ibotenate (up to 2mg/kg) had no anthelmintic activity against H. contortus in gerbils. When 1mg/kg ibotenate was used in combination with IVM, IVM efficacy increased by 15% ( P=0.048 ). These results demonstrate that a GluCl agonist enhances IVM activity and provides further information on the mode of action of ivermectin in parasitic nematodes.


Application of automated crystallography for transmission electron microscopy in the study of grain-boundary segregation.
Analytical Electron Microscopy (AEM) has brought significant progress in the study of grain-boundary segregation. Using X-ray energy-dispersive spectrometry (XEDS) in the AEM, elemental segregation information can be related to the crystallographic character of the same boundary via conventional Transmission Electron Microscope (TEM) diffraction techniques. While significant efforts have been made to improve XEDS analysis of sub-nanometer segregation layers, the methods for crystallographic characterization of grain boundaries have remained the same for several decades and labor-intensive processes. Recently, a method termed Automated Crystallography for TEM (ACT) was developed, which automates crystallographic characterization of grains under TEM observation. In the present work, we combine ACT and X-ray mapping via EDS in AEM for the study of Sb grain-boundary segregation in a rapidly solidified Cu-0.08 wt % Sb alloy. In contrast with previous reports, a large degree of anisotropy in Sb segregation level between different boundaries is found. ACT results suggest that one of the several grain boundaries observed with no detectable Sb segregation is very close to a Sigma 3 coincidence-site lattice structure. The reason for the observed anisotropy in the present alloy is discussed, based upon McLean's theory of segregation.


Anammox bacteria: from discovery to application.
Anaerobic ammonium oxidation (anammox) bacteria, which were discovered in waste-water sludge in the early 1990s, have the unique metabolic ability to combine ammonium and nitrite or nitrate to form nitrogen gas. This discovery led to the realization that a substantial part of the enormous nitrogen losses that are observed in the marine environment--up to 50% of the total nitrogen turnover--were due to the activity of these bacteria. In this Timeline, Gijs Kuenen recalls the discovery of these unique microorganisms and describes the continuing elucidation of their roles in environmental and industrial microbiology.


Double-Bundle Anterior Cruciate Ligament Reconstruction With Primary Repair and Hamstring Autograft Augmentation.
The optimal treatment of a ruptured anterior cruciate ligament (ACL) restores the patient's native anatomy and biomechanics as close to normal as possible. The purpose of this technical note is to describe an ACL reconstruction technique in which a double-bundle concept is used, wherein one bundle contains repaired ACL tissue and the second bundle contains a hamstring autograft, and each bundle is tensioned independently. Even in chronic cases, this technique allows for incorporation of the native ACL because, more often than not, there is sufficient tissue of good quality available for repair of one bundle. By augmenting the ACL repair with an autograft sized to the fit the individual anatomy, the patient's ACL tibial footprint can be closely restored to normal, and the potential benefits of tissue preservation are combined with the biomechanical strengths of an autograft double-bundle ACL reconstruction.


Facial trustworthiness dampens own-gender bias in emotion recognition.
Previous research suggests that emotion recognition is influenced by social categories derived by invariant facial features such as gender and inferences of trustworthiness from facial appearance. The current study sought to replicate and extend these findings by examining the intersection of these social categories on recognition of emotional facial expressions. We used a dynamic emotion recognition task to assess accuracy and response times in the happiness and anger categorization displayed by female and male faces that differed in the degree of facial trustworthiness (i.e., trustworthy- vs. untrustworthy-looking faces). We found that facial trustworthiness was able to modulate the own-gender bias on emotion recognition, as responses to untrustworthy-looking faces revealed a bias towards ingroup members. Conversely, when faces look trustworthy, no differences on emotion recognition between female and male faces were found. In addition, positive inferences of trustworthiness lead to faster recognition of happiness in females and anger in males, showing that facial appearance was able to influence also the intersection between social categories and specific emotional expressions. Together, these results suggest that facial appearance, probably due to the activation of approach or avoidance motivational systems, is able to modulate the own-gender bias on emotion recognition.


Modified Masquelet technique using allogeneic umbilical cord-derived mesenchymal stem cells for infected non-union femoral shaft fracture with a 12 cm bone defect: A case report.
Non-union due to large bone loss often causes significant long-term morbidity. We incorporate the use of allogeneic umbilical cord-derived mesenchymal stem cells (UC-MSCs) as part of the diamond concept of regenerative medicine in a case of infected non-union fracture. We reported a 54-year-old female patient presenting with pain on the right thigh. She was previously diagnosed with a closed fracture of the right femoral shaft and underwent four surgeries before finally being referred to Dr. Cipto Mangunkusumo General Hospital with infected non-union of the right femoral shaft. The patient was treated with a combination of UC-MSCs, bone morphogenetic protein-2 (BMP-2), Hydroxyapatite (HA), and mechanical stabilization using Masquelet Technique. The combination of allogeneic MSCs, BMP2, HA, and Masquelet Technique was successful in creating new bone with no apparent side effects. Bone loss might be caused by external factors (true defects), or structural loss of the existing bone. The combination of allogeneic UC-MSCs, BMP-2, HA and an induced membrane technique pioneered by Masquelet allowed for faster regeneration process and more optimal bone healing. This paper aims to assess and compare the result of such procedures with the previous four surgeries done to the patient, which did not yield satisfactory results. The application of allogeneic UC-MSC, BMP-2, HA and Masquelet technique as proposed in the diamond concept is a viable method in treating critical-sized bone defect and provides an effective way to overcome non-union caused by large defect.


Recent advances and challenges in the treatment of invasive fungal infections.
The frequency of invasive fungal infections (IFIs) has increased over the last decade with the rise in at-risk populations of patients. The morbidity and mortality of IFIs are high and management of these conditions is a great challenge. With the widespread adoption of antifungal prophylaxis, the epidemiology of invasive fungal pathogens has changed. Non-albicans Candida, non-fumigatus Aspergillus and moulds other than Aspergillus have become increasingly recognised causes of invasive diseases. These emerging fungi are characterised by resistance or lower susceptibility to standard antifungal agents. Invasive infections due to these previously rare fungi are therefore more difficult to treat. Recently developed antifungal agents provide the potential to improve management options and therapeutic outcomes of these infections. The availability of more potent and less toxic antifungal agents, such as second-generation triazoles and echinocandins, has led to considerable improvement in the treatment of IFIs. This article reviews the changing spectrum of invasive mycosis, the properties of recently developed antifungal agents and their role in the management of these infections.


Carbon nanothermometer containing gallium.
Many applications have been found for carbon nanotubes, and we can now add a role as a 'nanothermometer' to this list. We describe how the height of a continuous, unidimensional column of liquid gallium inside a carbon nanotube (up to about 10 micrometres long and about 75 nanometres in diameter) varies linearly and reproducibly in the temperature range 50-500 degrees C, with an expansion coefficient that is the same as for gallium in the macroscopic state. We chose gallium as our thermal indicator because it has one of the greatest liquid ranges of any metal (29.78-2,403 degrees C) and a low vapour pressure even at high temperatures. This nanothermometer should be suitable for use in a wide variety of microenvironments.


Nano/Micromotors for Diagnosis and Therapy of Cancer and Infectious Diseases.
Micromotors are man-made nano/microscale devices capable of transforming energy into mechanical motion. The accessibility and force offered by micromotors hold great promise to solve complex biomedical challenges. This Review highlights current progress and prospects in the use of nano and micromotors for diagnosis and treatment of infectious diseases and cancer. Motion-based sensing and fluorescence switching detection strategies along with therapeutic approaches based on direct cell capture; killing by direct contact or specific drug delivery to the affected site, will be comprehensively covered. Future challenges to translate the potential of nano/micromotors into practical applications will be described in the conclusions.


Synthesis and properties of caprolactone and ethylene glycol copolymers for neural regeneration.
Copolymer networks from poly(ethylene glycol) methacrylate (PEGMA) and caprolactone 2-(methacryloyloxy) ethyl ester were synthesized and the resulting structure of the copolymer network was characterized by differential scanning calorimetry, thermogravimetry, Fourier transform infrared spectroscopy, equilibrium water gain and dynamic mechanical analysis, results which were employed to conclude about the network structure of the resulting copolymers. The new material is a random copolymer with a good miscibility and increasing hydrophilicity as the PEGMA content increases in the composition. Physical data suggest an excess free volume and synergistic interactions between the lateral chains of both comonomers. Olfactory ensheathing cells were cultured on the different networks, and cell viability and proliferation were assessed by MTS assay. The copolymers with a 30 wt% of PEGMA showed the best results compared with the other compositions in this respect, indicating the relevance for biological performance of a balance of hydrophilic and hydrophobic functionalities in the polymer chain.


Labdane-type diterpenoids from the wood of Cunninghamia konishii.
Five new labdane-type diterpenes, 12beta,19-dihydroxymanoyl oxide (1), 8(17),13-labdadien-12,15-olid-19-oic acid (2), 12,15-epoxy-8(17),13-labdadien-18-oic acid (3), 8alpha-hydroxy-11E,13Z-labdadien-15-al (4), and (13R)-13-hydroxy-8(17), 11E,14-labdatrien-18-oic acid (5) were isolated from the wood of Cunninghamia konishii. Their structures were elucidated by two-dimensional NMR spectroscopy.


Myelopathy but normal MRI: where next?
For most patients presenting with a spinal cord syndrome MR scanning has become the key investigation in establishing the diagnosis. However, myelopathy with normal spinal imaging remains a common clinical conundrum. In this review we discuss the diagnoses to consider for the neurologist presented with a patient with "MR normal myelopathy". We will illustrate this scenario with a series of short cases and consider the further investigation of "MRI normal" myelopathy.


Unraveling the key driving factors involved in cometabolism enhanced aerobic degradation of tetracycline in wastewater.
Cometabolism has shown great potential in increasing the engineering feasibility of microalgae-based biotechnologies for the aerobic treatment of antibiotics-polluted wastewaters. Yet, the underlying mechanisms involved in improved microalgal performance remain unknown. In this study, we incorporated transcriptomics, gene network analysis, and enzymatic activities with cometabolic pathways of tetracycline (TC) by Chlorella pyrenoidosa to identify the key driving factors. The results demonstrated that cometabolism constructed a metabolic enzymes-photosynthetic machinery to improve the electron transport chain and activities of catalytic enzymes, which resulted in subsequent 100% removal of TC. Coupling formation dynamics of the intermediates with roles of identified metabolic enzymes, degradation of TC can be induced by de/hydroxylation, de/hydrogenation, bond-cleavage, decarboxylation, and deamination. Evaluation of 18 antibiotics' removal in reclaimed water showed cometabolism decreased the total concentrations of these antibiotics from 495.54 ng L-1 to 221.80 ng L-1. Our findings not only highlight the application potential of cometabolism in increasing engineering feasibility of microalgal degradation of antibiotics from wastewaters, but also provide the unique insights into unraveling the "black-box" of cometabolisms in aerobic biodegradation.


Recycling waste iron-rich algal flocs as cost-effective biochar activator for heterogeneous Fenton-like reaction towards tetracycline degradation: Important role of iron species and moderately defective structures.
Harvesting aquatic harmful algal blooms (HABs) and reusing them is a promising way for antibiotic degradation. Herein, a novel iron-rich biochar (Fe-ABC), derived from algal biomass harvested by magnetic coagulation, was successfully designed and fabricated as activator for heterogeneous Fenton-like reaction. The modification methods and pyrolysis temperatures (400-800 °C) were optimized to enhance the formation of rich iron species and moderately defective structure, yielding Fe-ABC-600 with enhanced electron transfer and H2O2 activation capability. Thus, Fe-ABC-600 exhibited superior removal efficiency (95.33%) on tetracycline (TC), where the presence of multiple iron species (Fe3+, Fe2+ and Fe4+) and moderately defective structure accelerating the Fenton-like oxidation. The concentration of leaching Fe after each reaction was all below 0.74 mg/L in five cycles, ensuring the sustained degradation. And •OH was proved to be the major radical contributing to the degradation of TC, as well as the direct electron transfer mechanism together, in which the CO acted as electron regulator and electron donor. Fe-ABC as a cost-effective catalyst has notable application potentials in TC removal from wastewater owing to its remarkable advantages of high resource utilization, enhanced catalytic property, high ecological safe, notable TC degradation efficiency, low cost and environmental-friendliness.


Effect of active versus passive void trials on time to patient discharge, urinary tract infection, and urinary retention: a randomized clinical trial.
We sought to determine the effect of active versus passive voiding trials on time to hospital discharge and rates of urinary tract infection (UTI) and urinary retention (UR). We performed a prospective, randomized trial comparing active (AVT) versus passive (PVT) void trials of inpatients requiring urethral catheter removal. Of 329 eligible patients, 274 were randomized to AVT (bladder filled with saline before catheter removal) or PVT (spontaneous bladder filling after catheter removal). Primary outcome was time to hospital discharge. Secondary outcomes were UTI (NSQIP criteria) and UR (requiring repeat catheterization) within 2 weeks of void trial. The median time to void was 18 (5-115) versus 236 (136-360) min in the AVT and PVT groups, respectively (p < 0.0001). However, no difference was seen in comparison of the median time to hospital discharge between AVT [28.4 (13.6-69.3) h] and PVT [30.0 (10.4-75.6) h] cohorts, respectively (p = 0.93). Six (4.8%) and 13 (12.9%) patients developed UTI in the AVT and PVT groups, respectively (p = 0.03). Eleven (8.8%) and 12 (11.9%) patients developed UR in the AVT and PVT groups, respectively (p = 0.36). Our study comparing AVT versus PVT demonstrated no difference in time to discharge despite a 3.6 h reduction in time to void associated with AVT. AVT was associated with a 63% reduction in UTI, with no difference seen in UR rates across cohorts. Given the reduction in UTI and technical advantages, our data suggest that AVT should be considered as a recommended technique for void trial protocol. NCT02886143 (clinicaltrials.gov).