Somatostatin analogues improve health-related quality of life in polycystic liver disease: a pooled analysis of two randomised, placebo-controlled trials.
Polycystic liver disease is associated with impaired health-related quality of life (HRQL). Somatostatin analogues reduce hepatomegaly in polycystic liver disease. To determine whether somatostatin analogues improve HRQL and to identify factors associated with change in HRQL in polycystic liver disease. We pooled data from two randomized, double-blind, placebo-controlled trials that evaluated HRQL using the Short-Form 36 (SF-36) in 96 polycystic liver disease patients treated 6-12 months with somatostatin analogues or placebo. The SF-36 contains a summarizing physical and mental component score and was administered at baseline and at the end of treatment. We used random effect models to delineate the effect of somatostatin analogues on HRQL. We determined the effect of demographics, height-adjusted liver volume, change in liver volume, somatostatin analogue-associated side effects with change in HRQL. In patients with autosomal dominant polycystic kidney disease, we estimated the effect of height-adjusted kidney volume and change in kidney volume in relation to HRQL. Physical component scores improved with somatostatin analogues, but remained unchanged with placebo (3.41 ± 1.29 vs. -0.71 ± 1.54, P = 0.044). Treatment had no impact on the mental component score. Large liver volume was independently associated with larger HRQL decline during follow up (-4.04 ± 2.02 points per logarithm liver volume, P = 0.049). In autosomal dominant polycystic kidney disease, patients with large liver and kidney volumes had larger decline in HRQL (5.36 ± 2.54 points per logarithm liver volume; P = 0.040 and -4.00 ± 1.88 per logarithm kidney volume; P = 0.039). Somatostatin analogues improve HRQL in symptomatic polycystic liver disease. Halting the progressive nature of polycystic liver disease is necessary to prevent further decline of HRQL in severe hepatomegaly.


Risk of subsequent primary oral cancer in a cohort of 69,460 5-year survivors of childhood and adolescent cancer in Europe: the PanCareSurFup study.
Survivors of childhood cancer are at risk of subsequent primary malignant neoplasms (SPNs), but the risk for rarer types of SPNs, such as oral cancer, is uncertain. Previous studies included few oral SPNs, hence large-scale cohorts are required to identify groups at risks. The PanCareSurFup cohort includes 69,460 5-year survivors of childhood cancer across Europe. Risks of oral SPNs were defined by standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence. One hundred and forty-five oral SPNs (64 salivary gland, 38 tongue, 20 pharynx, 2 lip, and 21 other) were ascertained among 143 survivors. Survivors were at 5-fold risk of an oral SPN (95% CI: 4.4-5.6). Survivors of leukaemia were at greatest risk (SIR = 19.2; 95% CI: 14.6-25.2) followed by bone sarcoma (SIR = 6.4, 95% CI: 3.7-11.0), Hodgkin lymphoma (SIR = 6.2, 95% CI: 3.9-9.9) and soft-tissue sarcoma (SIR = 5.0, 95% CI: 3.0-8.5). Survivors treated with radiotherapy were at 33-fold risk of salivary gland SPNs (95% CI: 25.3-44.5), particularly Hodgkin lymphoma (SIR = 66.2, 95% CI: 43.6-100.5) and leukaemia (SIR = 50.5, 95% CI: 36.1-70.7) survivors. Survivors treated with chemotherapy had a substantially increased risk of a tongue SPN (SIR = 15.9, 95% CI: 10.6-23.7). Previous radiotherapy increases the risk of salivary gland SPNs considerably, while chemotherapy increases the risk of tongue SPNs substantially. Awareness of these risks among both health-care professionals and survivors could play a crucial role in detecting oral SPNs early.


Molecular follow-up of preneoplastic lesions in bronchial epithelium of former Chernobyl clean-up workers.
Ionizing radiation is a potent lung carcinogen, but the precise molecular damage associated with it is still unknown. In this study we investigated cancer-related molecular abnormalities including K-ras (codon 12) mutation, p16(INK4A) promoter hypermethylation and microsatellite alterations at seven chromosomal regions in successive biopsies obtained from former Chernobyl cleanup workers in comparison with smokers and nonsmokers who have never had radiation exposure. Our results indicate that prolonged persistence of inhaled radioactive particles is associated with appearance of allelic loss at 3p12, 3p14.2 (FHIT), 3p21, 3p22-24 (hMLH1) and 9p21 (p16INK4A) in bronchial epithelium of former Chernobyl clean-up workers. The prevalence of 3p14.2 allelic loss was associated with decreased expression of the FHIT mRNA in their bronchial epithelium in comparison with control group of smokers. During several years of our monitoring samples of epithelium were collected from the same area of bronchial tree. In epithelium exposed to carcinogens (tobacco smoke and/or radioactivity) the total number of molecular abnormalities was significantly higher in dysplasia and in morphologically normal foci progressed later to dysplasia than in these samples which never showed evidence of such progression. Our findings indicate that extensive cancer-related molecular abnormalities sequentially occur in radiation damaged bronchial epithelium of former Chernobyl clean-up workers.


Perturbations in reward-related decision-making induced by reduced prefrontal cortical GABA transmission: Relevance for psychiatric disorders.
The prefrontal cortex (PFC) is critical for higher-order cognitive functions, including decision-making. In psychiatric conditions such as schizophrenia, prefrontal dysfunction co-occurs with pronounced alterations in decision-making ability. These alterations include a diminished ability to utilize probabilistic reinforcement in guiding future choice, and a reduced willingness to expend effort to receive reward. Among the neurochemical abnormalities observed in the PFC of individuals with schizophrenia are alterations in the production and function of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). To probe how PFC GABA hypofunction may contribute to alterations in cost/benefit decision-making, we assessed the effects GABAA-receptor antagonist bicuculline (BIC; 50 ng in 0.5 μl saline/hemisphere) infusion in the medial PFC of rats during performance on a series of well-validated cost/benefit decision-making tasks. Intra-PFC BIC reduced risky choice and reward sensitivity during probabilistic discounting and decreased the preference for larger rewards associated with a greater effort cost, similar to the behavioral sequelae observed in schizophrenia. Additional experiments revealed that these treatments did not alter instrumental responding on a progressive ratio schedule, nor did they impair the ability to discriminate between reward and no reward. However, BIC induced a subtle but consistent impairment in preference for larger vs. smaller rewards of equal cost. BIC infusion also increased decision latencies and impaired the ability to "stay on task" as indexed by reduced rates of instrumental responding. Collectively, these results implicate prefrontal GABAergic dysfunction as a key contributing factor to abnormal decision-making observed in schizophrenia and other neuropsychiatric conditions with similar neurobiological and behavioral alterations.


The decreased metastatic potential of rhabdomyosarcoma cells obtained through MET receptor downregulation and the induction of differentiation.
Rhabdomyosarcoma (RMS) is the most common type of pediatric soft tissue sarcoma. The MET receptor has an important role in the biology of RMS, and its overexpression and hyperactivation correlate with the metastatic ability of RMS. Consequently, interfering with MET expression or functionality may constitute a sound strategy for reducing the progression and metastatic potential of RMS. Our study reveals that downregulation of the MET receptor leads to changes in the morphology of ARMS cell in vivo. Tumors acquire a spindle shape that is characteristic of muscle fibers. Inhibition of MET expression or function leads to (i) a decreased expression of the early myogenic marker MyoD, (ii) a decreased ability of ARMS cells to metastasize to bone marrow cavities, (iii) downregulation of CXCR4 receptor expression and (iv) a decreased migration of MET-depleted cells towards gradients of HGF and SDF-1. Finally, we demonstrate that in vitro differentiation of alveolar RMS cells decreases their metastatic behavior by reducing both the expression of the MET and CXCR4 receptors and their migratory response to HGF and SDF-1. These findings suggest that blockers of MET receptor function and inducers of RMS cells differentiation may be clinically useful for reducing the aggressiveness and metastatic potential of RMS and may have significant implications for its treatment.


Yiqi Fumai Injection as an Adjuvant Therapy in Treating Chronic Heart Failure: A Meta-Analysis of 33 Randomized Controlled Trials.
Yiqi Fumai injection (YQFM) is a traditional Chinese medicine widely used for cardiovascular diseases in China. This systematic review aimed to evaluate whether YQFM could be an effective and safe complementary therapy for chronic heart failure (CHF). Eight electronic literature databases were searched up to March 31, 2020. Randomized controlled trials (RCTs) comparing YQFM + conventional treatment with conventional treatment alone for CHF were included. The primary outcome was response to treatment, which was graded by improvements in heart function based on the New York Heart Association (NYHA) criteria, while the secondary outcomes included the left ventricular ejection fraction (LVEF), cardiac output, left ventricular end-systolic diameter (LVESD), amino-terminal pro-brain natriuretic peptide (NT-proBNP), 6-minute walk test performance (6MWT), quality of life (QoL) as assessed by the Minnesota Living with Heart Failure questionnaire, and adverse reactions. Data from individual RCTs were pooled by a random-effects meta-analysis with effect measures of proportional odds ratios (pORs) and 95% confidence intervals (95% CIs) for the ordinal outcomes and the mean difference (MD) and 95% CI for the continuous outcomes. In total, 33 RCTs involving 3070 patients with an overall moderate-to-high risk of bias were selected. The meta-analysis showed that compared with conventional treatment alone, YQFM plus conventional treatment had a significantly higher likelihood of improving the response to treatment (pOR 1.88, 95% CI 1.47 to 2.42, I 2 = 0%). YQFM also significantly improved the LVEF (MD 5.53%, 95% CI 4.73 to 6.33, I 2 = 82%), cardiac output (MD 0.32 L/min, 95% CI 0.19 to 0.45, I 2 = 47%), and LVESD (MD -3.73 mm, 95% CI -5.51 to -1.95, I 2 = 22%), reduced the NT-proBNP levels (MD -341.83 pg/mL, 95% CI -417.89 to -265.77, I 2 = 88%), and improved the 6MWT (MD 61.86 m, 95% CI 45.05 to 78.67, I 2 = 64%) and QoL (MD -9.82, 95% CI -14.17 to -5.46, I 2 = 81%). No serious adverse events related to YQFM were reported. Although limited by a moderate-to-high risk of bias, the current evidence suggests that YQFM as a complementary treatment significantly improves heart function and related indicators in patients with CHF. The clinical use of YQFM needs careful safety monitoring. Well-designed studies are still required to further evaluate the efficacy and safety of YQFM for CHF.


Pancreatic β-cell glutaminase 2 maintains glucose homeostasis under the condition of hyperglycaemia.
Glutaminase 2 (GLS2), a master regulator of glutaminolysis that is induced by p53 and converts glutamine to glutamate, is abundant in the liver but also exists in pancreatic β-cells. However, the roles of GLS2 in islets associated with glucose metabolism are unknown, presenting a critical issue. To investigate the roles of GLS2 in pancreatic β-cells in vivo, we generated β-cell-specific Gls2 conditional knockout mice (Gls2 CKO), examined their glucose homeostasis, and validated the findings using a human islet single-cell analysis database. GLS2 expression markedly increased along with p53 in β-cells from control (RIP-Cre) mice fed a high-fat diet. Furthermore, Gls2 CKO exhibited significant diabetes mellitus with gluconeogenesis and insulin resistance when fed a high-fat diet. Despite marked hyperglycaemia, impaired insulin secretion and paradoxical glucagon elevation were observed in high-fat diet-fed Gls2 CKO mice. GLS2 silencing in the pancreatic β-cell line MIN6 revealed downregulation of insulin secretion and intracellular ATP levels, which were closely related to glucose-stimulated insulin secretion. Additionally, analysis of single-cell RNA-sequencing data from human pancreatic islet cells also revealed that GLS2 expression was elevated in β-cells from diabetic donors compared to nondiabetic donors. Consistent with the results of Gls2 CKO, downregulated GLS2 expression in human pancreatic β-cells from diabetic donors was associated with significantly lower insulin gene expression as well as lower expression of members of the insulin secretion pathway, including ATPase and several molecules that signal to insulin secretory granules, in β-cells but higher glucagon gene expression in α-cells. Although the exact mechanism by which β-cell-specific GLS2 regulates insulin and glucagon requires further study, our data indicate that GLS2 in pancreatic β-cells maintains glucose homeostasis under the condition of hyperglycaemia.


[Evaluation of orthopantomographic X-ray technique in the diagnosis of impacted upper canine].
In this article advantages and disadvantages of orthopantomographic x-ray technique in the diagnosis of the impacted tooth are discussed. Twenty patients were examined by orthopantomographic technique as well as by standard retroalveolar radiographs. The investigation showed that the orthopantomographic technique was not a predominant method in the diagnosis of maxillar impacted canine and that the standard retroalveolar method was more reliable.


Zika virus genome biology and molecular pathogenesis.
Zika virus (ZIKV) is an emerging RNA virus in the widespread Flavivirus genus. Recently, ZIKV has rapidly spread around the world and has been implicated in human disease, including neurological disorders, triggering public and scientific attention. Understanding how ZIKV causes disease is the highest priority, yet little is known about this virus. Here we examine the currently published data from ZIKV studies to provide the latest understanding of ZIKV genome biology and molecular pathogenesis. The ZIKV genome evolved rapidly from the Flavivirus genus and diverged from the members of this genus, even within the dengue virus cluster to which ZIKV belongs. Genome variations and divergences also exist among ZIKV strains/isolates. These genome divergences might account for the uniqueness of Zika disease. ZIKV infection activates not only the antiviral immune response but also the pro-inflammatory responses associated with disease symptoms. Strikingly, ZIKV activates protein complexes that are functionally associated with disease process, such as glial cell activation and proliferation (for example, Toll-like receptors), apoptosis and cell death, and inflammation. The activation of these complexes may critically contribute to Zika disease. The novel insights into ZIKV genome divergence and disease mechanisms summarized in this review will help accelerate the development of anti-ZIKV strategies.


An improved method for increasing the resolution and sensitivity of silver staining of nucleic acid bands in polyacrylamide gels.
Staining of polyacrylamide gels with methylene blue prior to silver staining increases band resolution and sensitivity. This method permits resolution of multiple bands less than 1 mm apart, and is able to detect bands containing only 100 pg of RNA.


Neuromuscular Fatigue and Metabolism during High-Intensity Intermittent Exercise.
To examine the degree of neuromuscular fatigue development along with changes in muscle metabolism during two work-matched high-intensity intermittent exercise protocols in trained individuals. In a randomized, counter-balanced, crossover design, 11 endurance-trained men performed high-intensity intermittent cycle exercise protocols matched for total work and including either multiple short-duration (18 × 5 s; SS) or long-duration (6 × 20 s; LS) sprints. Neuromuscular fatigue was determined by preexercise to postexercise changes in maximal voluntary contraction force, voluntary activation level and contractile properties of the quadriceps muscle. Metabolites and pH were measured in vastus lateralis muscle biopsies taken before and after the first and last sprint of each exercise protocol. Peak power output (11% ± 2% vs 16% ± 8%, P < 0.01), maximal voluntary contraction (10% ± 5% vs 25% ± 6%, P < 0.05), and peak twitch force (34% ± 5% vs 67% ± 5%, P < 0.01) declined to a lesser extent in SS than LS, whereas voluntary activation level decreased similarly in SS and LS (10% ± 2% vs 11% ± 4%). Muscle [phosphocreatine] before the last sprint was 1.5-fold lower in SS than LS (P < 0.001). Preexercise to postexercise intramuscular accumulation of lactate and H was twofold and threefold lower, respectively, in SS than LS (P < 0.001), whereas muscle glycogen depletion was similar in SS and LS. Rate of muscle glycolysis was similar in SS and LS during the first sprint, but twofold higher in SS than LS during the last sprint (P < 0.05). These findings indicate that, in endurance-trained individuals, multiple long-sprints induce larger impairments in performance along with greater degrees of peripheral fatigue compared to work-matched multiple short-sprints, with these differences being possibly attributed to more extensive intramuscular accumulation of lactate/H and to lower rates of glycolysis during multiple long-sprint exercise.


Relative rates of insertion and deletion mutations in dinucleotide repeats of various lengths in mismatch repair proficient mouse and mismatch repair deficient human cells.
Microsatellites are DNA elements composed of short tandem repeats of 1-5bp. These sequences are particularly prone to frameshift mutation by insertion-deletion loop formation during replication. The mismatch repair system is responsible for correcting these replication errors, and microsatellite mutation rates are significantly elevated in the absence of mismatch repair. We have investigated the effect of varying the number of repeats in a (CA)n microsatellite on mutation rates in cultured mammalian cells proficient or deficient in mismatch repair. We have also compared the relative rates of single-repeat insertions and deletions in these cells. Two plasmid vectors were constructed for each repeat unit number (n=8, 17, and 30), such that the microsatellites, placed upstream of a bacterial neomycin resistance gene (neo), disrupted the reading frame of the gene in the (-1) or (+1) direction. Plasmids were introduced separately into the cells, where they integrated into the cellular genome. Mutation rates were determined by selection of clones with frameshift mutations in the microsatellite that restored the reading frame of the neo gene. We found that mutation rates were significantly higher for (CA)17 and (CA)30 tracts than for (CA)8 tracts in both mismatch repair proficient (mouse) and deficient (human) cells. A mutational bias favoring insertions was generally observed. In both (CA)17 and (CA)30 tracts, single-repeat insertion rates were higher than single-repeat deletion rates with or without mismatch repair; deletions of multiple repeat units (> or =8bp) were observed in these tracts, where as deletions this large were not found in the (CA)8 tract. Single-repeat mutations of both types were made at similar rates in (CA)8 tracts in human mismatch repair deficient (MMR-) cells, but single-repeat insertion rates were higher than single-repeat deletion rates in mouse mismatch repair proficient (MMR+) cells. Results of these direct studies on microsatellite mutations in cultured cells should be useful for refinement of mathematical models for microsatellite evolution.


Using multiple imputation and intervention-based scenarios to project the mobility of older adults.
Projections of the development of mobility limitations of older adults are needed for evidence-based policy making. The aim of this study was to generate projections of mobility limitations among older people in the United States, England, and Finland. We applied multiple imputation modelling with bootstrapping to generate projections of stair climbing and walking limitations until 2026. A physical activity intervention producing a beneficial effect on self-reported activities of daily living measures was identified in a comprehensive literature search and incorporated in the scenarios used in the projections. We utilised the harmonised longitudinal survey data from the Ageing Trajectories of Health - Longitudinal Opportunities and Synergies (ATHLOS) project (N = 24,982). Based on the scenarios from 2012 to 2026, the prevalence of walking limitations will decrease from 9.4 to 6.4%. A physical activity intervention would decrease the prevalence of stair climbing limitations compared with no intervention from 28.9 to 18.9% between 2012 and 2026. A physical activity intervention implemented on older population seems to have a positive effect on maintaining mobility in the future. Our method provides an interesting option for generating projections by incorporating intervention-based scenarios.


Implantation of the Artisan iris reconstruction intraocular lens in 5 children with aphakia and partial aniridia caused by perforating ocular trauma.
To describe the long-term clinical results of the implantation of the Artisan iris reconstruction IOL in 5 eyes of 5 children for aphakia and partial aniridia attributable to penetrating ocular trauma. The charts of 5 children were retrospectively reviewed. The nature and the extent of injury; age at IOL implantation; visual, refractive, and cosmetic outcome; endothelial cell density; and complications and subsequent surgical interventions were evaluated. Mean follow-up period was 8.9 years (range, 4.9-12.4). Mean age at implantation of the Artisan iris reconstruction IOL was 9.5 years (range, 7.7-12.7). Visual acuity improved in 2 of 5 eyes, remained stable in 2 of 5 eyes, and decreased in 1 of 5 eyes. Complaints of photophobia were reduced, and a satisfactory cosmetic outcome was achieved in 3 of 5 patients. The mean spherical equivalent refraction error at last follow-up was -4.0 D. Mean endothelial cell loss when compared with the healthy fellow eye was 42%. Two cases were complicated by partial luxation of the IOL, one case by persistent anterior uveitis and secondary glaucoma. One eye developed a retinal detachment. The Artisan iris reconstruction IOL is a treatment option for the treatment of aniridia and aphakia due to penetrating ocular trauma in children. We emphasize the high-risk characteristics of the eyes treated and the importance of careful patient selection in the outcome of the implantation of the Artisan iris reconstruction IOL.


Degree and Duration of Functional Improvement on Long-Term Follow-Up of Spinal Dural Arteriovenous Fistulae Occluded by Endovascular and Surgical Treatment.
Long-term outcomes following occlusion of spinal dural arteriovenous fistula (SDAVF) are poorly understood and are based on small series reporting predominantly short-term outcomes. The degree and duration of improvement remain unclear. In this study, we analyzed long-term outcomes following occlusion in a cohort of patients with SDAVF. This was a single-center cohort study of patients with SDAVF identified from a prospective database. Outcomes were assessed using a modified Aminoff and Logue Disability (ALD) Scale, the modified Rankin Scale (mRS), and patient-reported outcomes at presentation and long-term follow-up. Both angiographic recanalization and idiopathic functional recurrence rates were calculated. Of the total of 67 patients with SAVDF identified, 59 were eligible for inclusion in this study. Fifty-seven of these 59 (97%) underwent occlusion. Twenty-two patients underwent initial embolization; 12 were occluded. Two patients recanalized. Eleven patients underwent surgery after attempted embolization; 10 were occluded. Thirty-seven patients treated by surgery only were occluded. The median duration of follow-up was 63 months (range, 12-240 months). After occlusion, the ALD gait and urinary scores improved by a median of 1 point. Although the median mRS score was unchanged, 49% of the patients experienced improvement, most by 1 point. There was no difference between the patients occluded by embolization or surgery, but those requiring both approaches had worse gait and urinary scores (P = 0.005 and 0.03, respectively). The duration of symptoms by itself had no effect on outcomes (P = 0.61). Following occlusion, 5 patients experienced an idiopathic late functional deterioration. Of 16 patients presenting with paraplegia, 13 (81%) improved, with a median mRS improvement of 1 point. Following occlusion, patients with SDAVF experienced a modest improvement in symptoms, most commonly by 1 point on the ALD scale. Idiopathic late deterioration was seen in 9.1% of patients.


Face perception in pure alexia: Complementary contributions of the left fusiform gyrus to facial identity and facial speech processing.
Recent concepts of cerebral visual processing predict from overlapping patterns of face and word activation in cortex that left fusiform lesions will not only cause pure alexia but also lead to mild impairments of face processing. Our goal was to determine if alexic subjects had deficits in facial identity processing similar to those seen after right fusiform lesions, or complementary deficits affecting different aspects of face processing. We studied four alexic patients whose lesions involved the left fusiform gyrus and one prosopagnosic subject with a right fusiform lesion, on standard tests of face perception and recognition. We evaluated their ability first to process faces in linear contour images, and second to detect, discriminate, identify and integrate facial speech patterns into perception. We found that all five patients were impaired in face matching across viewpoint, but the alexic subjects performed worse with line-drawn faces, while the prosopagnosic subject did not. Alexic subjects could detect facial speech patterns but had trouble identifying them and did not integrate facial speech patterns with speech sounds, whereas identification and integration was intact in the prosopagnosic subject. We conclude that, in addition to their role in reading, the left-sided regions damaged in alexic subjects participate in the perception of facial identity but in a non-redundant fashion, focusing on the information in linear contours at higher spatial frequencies. In addition they have a dominant role in processing facial speech patterns, another visual aspect of language processing.


Climate variability and seasonal patterns of paediatric parainfluenza infections in the tropics: An ecological study in Singapore.
Evidence of the relationship between climate variability, air pollution and human parainfluenza virus (HPIV) infections has been inconsistent. We assessed this in a paediatric population from a highly urbanized tropical city-state. We analysed all reports of HPIV infections in children <5 years old obtained from a major specialist women and children's hospital in Singapore. Assuming a negative binomial distribution and using multivariable fractional polynomial modelling, we examined the relations between climate variability, air quality and the risk of HPIV infections, adjusting for time-varying confounders. We identified 6393 laboratory-confirmed HPIV infections from 2009 to 2019. Every 1 °C decline in temperature was associated with a 5.8% increase (RR: 0.943, 95% Confidence Interval [95% CI]: 0.903-0.984) in HPIV infection risk 6 days later. Every 10% decrease in relative humidity was associated with a 15.8% cumulative increase in HPIV risk over the next 6 days (cumulative RR: 0.842, 95% CI: 0.771-0.919). Rainfall was positively associated with HPIV risk 2 days later (RR: 1.021, 95% CI: 1.000-1.043). A within-year seasonal rise of HPIV was driven by HPIV-3 and HPIV-1 and preceded by a seasonal decline in temperature. Gender was an effect modifier of the climate-HPIV relationship. Air quality was not associated with HPIV risk. This study demonstrates a close association between HPIV infection risk and tropical climate variability. The climate dependence and seasonal predictability of HPIV can inform the timing of community campaigns aimed at reducing infection risk and the development of hospital resources and climate adaption plans.


In situ preparation of a multifunctional adsorbent by optimizing the Fe2+/Fe3+/Mn2+/HA ratio for simultaneous and efficient removal of Cd(II), Pb(II), Cu(II), Zn(II), As(III), Sb(III), As(V) and Sb(V) from aqueous environment: Behaviors and mechanisms.
Multiple potentially toxic elements (PTEs) often coexist in practical wastewater environment, which poses serious risks to the ecological environment and human health. However, few of the reported adsorbents are capable of simultaneously and effectively removing multiple PTEs from wastewater due to the unique properties of each element. In this work, a multifunctional adsorbent FMHs was developed by optimizing Fe2+/Fe3+/Mn2+/HA ratio, and applied to remove Cd(II), Pb(II), Cu(II), Zn(II), As(III), Sb(III), As(V) and Sb(V) from aqueous solution. Results revealed that the adsorption data obeyed the Elovich, Sips and Redlich-Peterson models in the mono-component system, and the maximum adsorption capacity of FMHs was superior to most adsorbents reported in the literatures. In addition, FMHs retained considerable removal capacity after four cycles, and maintained excellent adsorption performance under the interference of different environmental factors (including pH, ionic strength, co-existing ions and humic acid). In the multi-component system, FMHs also presented high adsorption capacity for all the selected PTEs, especially for Sb(III/V) and Pb(II). Characterization results confirmed that various removal mechanisms, such as precipitation, surface complexation, ion exchange, electrostatic attraction and redox, were responsible for the capture of PTEs by FMHs.


High affinity, selective neurokinin 2 and neurokinin 3 receptor antagonists from a common structural template.
High affinity, selective hNK2 or hNK3 ligands can be prepared from the common template 1 in a few simple chemical operations. The hNK3 ligands 3 antagonise the calcium mobilisation caused by activation of hNK3 receptors expressed in CHO cells as measured using fura-2 microspectrofluorimetry.


Patient Satisfaction and Regret After Robot-assisted Radical Prostatectomy: A Decision Regret Analysis.
To assess treatment satisfaction and decision regret post robot-assisted radical prostatectomy (RARP) and correlate these with clinical, demographic and quality of life indicators. Our study took place at a high-volume United Kingdom center and patients were assessed at a minimum of 18 months postsurgery. Patients who underwent RARP between June 2011 and May 2016 were invited to participate through mailed questionnaires. A total of 207 patients formed our cohort. The questionnaires included European Organization for Research and Treatment of Cancer Quality of Life of Cancer patients 30 and PR25 modules, sexual health inventory in men and Likert decisional regret scale. A Decisional Regret Scale score of >15 was used to define an outcome of high decision regret. The mean patient age was 63 years and the mean duration of follow up was 36 months. Of the 106 responders, 51 (48%) were fully satisfied with the decision to undergo RARP and 32 (30%) recorded high regret. The mean Decisional Regret Scale score was 11.3. High decision regret associated with the length of time from RARP to questionnaire administration, higher prostate specific quality of life symptom scores and lower sexual and erectile function scores. Our study represents the first contemporary United Kingdom series assessing decision regret following the management of localised prostate cancer with RARP. Higher regret was seen in one third of patients and was associated with worse disease-specific quality of life, sexual and erectile function measures. To minimize regret, collaborative and detailed discussion should take place pre-operatively when counselling patients about RARP. The potential longevity and impact on quality of life of these side effects should be made clear.


First-trimester septated cystic hygroma, marked non-immune fetal hydrops, 45,X and coarctation of the aorta with neonatal survival.
Marked first-trimester nonimmue hydrops fetalis and 45,X with neonatal survival.


Streptomyces boncukensis sp. nov., isolated from saltern soil.
A novel Gram-stain positive, aerobic, non-motile Actinobacterium, designated strain SB3404T, was isolated from saltern soil collected from Boncuk Saltern, Sungurlu-Çorum, Turkey, and subjected to a polyphasic taxonomic approach. The organism has shown to have phylogenetic, chemotaxonomic, cultural and morphological properties consistent with its classification in the genus Streptomyces. 16S rRNA gene sequence analysis of strain SB3404T showed that it is closely related to Streptomyces albus NBRC 13014T (97.2% sequence similarity), Streptomyces xishensis YIM M 10378T (96.7%) and Streptomyces abyssalis YIM M 10400T (96.5%). The cell wall of the strain contained LL-diaminopimelic acid and the cell-wall sugars were glucose, mannose and ribose. The predominant menaquinones were identified as MK-9(H8) and MK-9(H6). The major cellular fatty acids were found to be iso-C16:0, anteiso-C17:0 and anteiso-C15:0. Consequently, strain SB3404T is considered to represent a novel species in the genus Streptomyces, for which the name Streptomyces boncukensis sp. nov. is proposed. The type strain is SB3404T (= KCTC 49371T = JCM 34018T).


Correction: Bio-related applications of porous organic frameworks (POFs).
Correction for 'Bio-related applications of porous organic frameworks (POFs)' by He Zhang et al., J. Mater. Chem. B, 2019, 7, 2398-2420, https://doi.org/10.1039/C8TB03192D.


TEAD4 overexpression suppresses thyroid cancer progression and metastasis in vitro by modulating Wnt signaling.
TEAD4 has been reported to act as an oncogenic gene in various types of cancer. This study intends to investigate the role and regulatory mechanism of TEAD4 in thyroid cancer (TC). GEPIA was used to predict the expression pattern of TEAD4 in TC. Expressions of TEAD4 and wnt3a in TC tissues and cells were analyzed by qRT-PCR and Western blot. TC cells were transfected with TEAD4 overexpression plasmids and treated with or without IWR-1-endo (a Wnt signaling inhibitor), and then TC cell viability, migration and invasion were assessed by MTT and Transwell assay. Expressions of E-cadherin, N-cadherin and Vimentin in cells were analyzed by Western blot. TEAD4 was low-expressed in TC tissues and cells. TEAD4 overexpression inhibited the viability, inhibited migration and invasion of TC cells, and downregulated N-cadherin and Vimentin expression, while promoted E-cadherin and wnt3a expression. The wnt3a expression was positively correlated with TEAD4 expression in TC. IWR-1-endo treatment reversed the effect of TEAD4 in TC cells. TEAD4 overexpression suppresses TC progression and metastasis in vitro through modulating Wnt signaling.


Mobilization of intracellular calcium in cultured vascular smooth muscle cells by uridine triphosphate and the calcium ionophore A23187.
The known action of uridine triphosphate (UTP) to contract some types of vascular smooth muscle, and the present finding that it is more potent than adenosine triphosphate in eliciting an increase in cytosolic Ca2+ concentration in aortic smooth muscle, led us to investigate the mode of action of this nucleotide. With this aim, cultured bovine aorta cells were subjected to patch-clamp methodologies under various conditions. Nucleotide-induced variations in cytosolic Ca2+ were monitored by using single channel recordings of the high conductance Ca(2+)-activated K+ (Maxi-K) channel within on-cell patches as a reporter, and whole-cell currents were measured following perforation of the patch. In cells bathed in Na(+)-saline, UTP (> 30 nM) induced an inward current, and both Maxi-K channel activity and unitary current amplitude of the Maxi-K channel transiently increased. Repetitive exposures elicited similar responses when 5 to 10 min wash intervals were allowed between challenges of nucleotide. Oscillations in channel activity, but not oscillation in current amplitude were frequently observed with UTP levels > 0.1 microM. Cells bathed in K+ saline (150 mM) were less sensitive to UTP (approximately 5-fold), and did not show an increase in unitary Maxi-K current amplitude. Since the increase in amplitude occurs due to depolarization of the cell membrane, a change in amplitude was not observed in cells previously depolarized with K+ saline. The enhancement of Maxi-K channel activity in the presence of UTP was not diminished by Ca2+ entry blockers or by removal of extracellular Ca2+. However, in the latter case, repetitive responses progressively declined. These observations, as well as data comparing the action of low concentrations of Ca2+ ionophores (< 5 microM) to that of UTP indicate that both agents elevate cytosolic Ca2+ by mobilization of this ion from intracellular pools. However, the Ca2+ ionophore did not cause membrane depolarization, and thus did not change unitary current amplitude. The effect of UTP on Maxi-K channel activity and current amplitude was blocked by pertussis toxin and by phorbol 12-myristate 13-acetate (PMA), but was not modified by okadaic acid, or by inhibitors of protein kinase C (PKC). Our data support a model in which a pyrimidinergic receptor is coupled to a G protein, and this interaction mediates release of Ca2+ from intracellular pools, presumably via the phosphatidyl inositol pathway. This also results in activation of membrane channels that give rise to an inward current and depolarization. Ultimately, smooth muscle contraction ensues.(ABSTRACT TRUNCATED AT 400 WORDS)


Detection of mild cognitive impairment in Parkinson's disease using gradient boosting decision tree models based on multilevel DTI indices.
Cognitive dysfunction is the most common non-motor symptom in Parkinson's disease (PD), and timely detection of a slight cognitive decline is crucial for early treatment and prevention of dementia. This study aimed to build a machine learning model based on intra- and/or intervoxel metrics extracted from diffusion tensor imaging (DTI) to automatically classify PD patients without dementia into mild cognitive impairment (PD-MCI) and normal cognition (PD-NC) groups. We enrolled PD patients without dementia (52 PD-NC and 68 PD-MCI subtypes) who were assigned to the training and test datasets in an 8:2 ratio. Four intravoxel metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), and two novel intervoxel metrics, local diffusion homogeneity (LDH) using Spearman's rank correlation coefficient (LDHs) and Kendall's coefficient concordance (LDHk), were extracted from the DTI data. Decision tree, random forest, and eXtreme gradient boosting (XGBoost) models based on individual and combined indices were built for classification, and model performance was assessed and compared via the area under the receiver operating characteristic curve (AUC). Finally, feature importance was evaluated using SHapley Additive exPlanation (SHAP) values. The XGBoost model based on a combination of the intra- and intervoxel indices achieved the best classification performance, with an accuracy of 91.67%, sensitivity of 92.86%, and AUC of 0.94 in the test dataset. SHAP analysis showed that the LDH of the brainstem and MD of the right cingulum (hippocampus) were important features. More comprehensive information on white matter changes can be obtained by combining intra- and intervoxel DTI indices, improving classification accuracy. Furthermore, machine learning methods based on DTI indices can be used as alternatives for the automatic identification of PD-MCI at the individual level.


Amplatzer device closure of a residual aortopulmonary window.
Significant residual defects after surgical closure of aortopulmonary windows have previously required re-operation. In this paper, we describe the use of a custom made Amplatzer closure device to occlude a hemodynamically significant defect in a 5-year-old child. The device was successfully deployed without complication, and resulted in a major reduction in aorto-pulmonary flow.


Evolution of porosity in geotechnical composites.
Nuclear magnetic resonance (NMR) (H1) transverse relaxation measurements were carried out on 37x70-mm cylindrical mineral/organic composites to determine and monitor the porosity evolution. Porosity is related, in principle, to the stability of such materials in geotechnical applications, for example, engineering foundations. The specimens represented novel formulations of mixed "wastes" containing coarse screened mineral, digested sewage sludge, quicklime, and pulverized fuel ash mixed and compacted together to form mechanically competent material. The measurements on a selected formulation indicated initially low porosity (<12%) that becomes lower over 6 months ( approximately 8%) due to pozzolanic reactions occurring. A relaxation time cutoff of 1.5 ms between "bound" and 'mobile' pore water much lower than sandstones (33 ms) was observed. The results confirmed that the NMR method allows a more reliable assessment of porosity and pore-size evolution.


M4Raw: A multi-contrast, multi-repetition, multi-channel MRI k-space dataset for low-field MRI research.
Recently, low-field magnetic resonance imaging (MRI) has gained renewed interest to promote MRI accessibility and affordability worldwide. The presented M4Raw dataset aims to facilitate methodology development and reproducible research in this field. The dataset comprises multi-channel brain k-space data collected from 183 healthy volunteers using a 0.3 Tesla whole-body MRI system, and includes T1-weighted, T2-weighted, and fluid attenuated inversion recovery (FLAIR) images with in-plane resolution of ~1.2 mm and through-plane resolution of 5 mm. Importantly, each contrast contains multiple repetitions, which can be used individually or to form multi-repetition averaged images. After excluding motion-corrupted data, the partitioned training and validation subsets contain 1024 and 240 volumes, respectively. To demonstrate the potential utility of this dataset, we trained deep learning models for image denoising and parallel imaging tasks and compared their performance with traditional reconstruction methods. This M4Raw dataset will be valuable for the development of advanced data-driven methods specifically for low-field MRI. It can also serve as a benchmark dataset for general MRI reconstruction algorithms.


COVID-19 risks and systemic gaps in Nigeria: resilience building lessons for pandemic and climate change management.
Pandemics alter a lot of human activities and the COVID-19 outbreak of 2020 was no exception. The COVID-19 pandemic, like climate change, has far-reaching consequences that transcend geographical boundaries. The COVID-19-induced disruptions were global and rapid and so are emerging climate change impacts which are slow on set. The consequent closure of businesses and public facilities translated to economic grounding which invariably took a toll on people. The extensive impact across various facets of society highlights the complex interrelationship often overlooked by most people. Although most African countries escaped the wrath of the disease, the lessons from the pandemic must be learnt and mainstreamed into managing the impacts of climate change. This paper attempts to draw lessons from recent developments and gaps experienced in the handling of the COVID-19 pandemic in Nigeria and how improvements can be made in managing climate change. The analysis identified gaps in the management of COVID-19 in Nigeria. These gaps are evident in the current management of climate change impact and mitigation. The paper highlighted lessons from the pandemic in Nigeria that are vital in the management of climate change. The paper identified supply chain resilience and circularity, overhauling of health insurance programmes, diversification for growth, reorientation of priorities, and the building of agile and responsive institutions as practical approaches to mainstream lessons from the pandemic for climate change impact management. Furthermore, adequate investment in preparedness, risk education, research and development, and integrated data infrastructure is vital to ensure the lessons become part of the consciousness of the people.


Dermatological manifestations of hematologic neoplasms. Part I: secondary specific skin lesions.
Cutaneous manifestations occur during the course of hematologic malignancies and precede, follow, or are late events in relation to the diagnosis. They result from paraneoplastic phenomena, tumor infiltrations, and immunosuppression resulting from the hematologic neoplasia itself or its treatment. The dermatologist must be aware of these conditions, which can help both in the diagnosis of the underlying disease and in the reduction of patient morbidity. This review (part I) addresses skin lesions associated with direct infiltration by systemic hematologic malignancies.


Quantitative structure-retention relationship studies of odor-active aliphatic compounds with oxygen-containing functional groups.
High-quality regression equations (R greater than 0.996) modeling the gas chromatographic retention indices of 115 odor-active compounds on stationary phases of different polarity are generated by using the ADAPT software system. Multiple linear regression techniques are used to describe the statistical relationship between the Kováts retention indices and structure-based molecular descriptors. These descriptors encode topological, geometrical, and electronic features of the molecules. The utility of several new descriptors encoding functions of partial atomic charge and solvent accessible surface area is demonstrated. Quantitative predictions of odor threshold values for a subset of these compounds containing the alcohol functional group are also calculated by using a similar methodology.


Ultrasound Guided Catheter Tip Location in Neonates: A Prospective Cohort Study.
To assess point-of-care-ultrasound (POCUS) guided catheter tip location in a neonatal cohort after insertion of percutaneously inserted central catheters (PICCs) from the upper part of the body. This was a prospective, observational study on PICC tip location. Tip site was assessed by radiological landmarks or direct ultrasound (US) visualization of the cardiovascular structures. One hundred eighteen PICCs (28Gauge/1French) were studied in 102 neonates (mean postmenstrual age 31 weeks, range 25-43 weeks; mean weight at positioning 1365 g, range 420-4180 g). Feasibility of POCUS guided tip location was 92.3% in our population. Failures were significantly associated with mechanical ventilation (aOR 5.33; 95% CI 1.13-29.5; P = .038). Agreement between US and radiographic methods was found in 88 of 109 cases (80.7%). Fifteen of 21 discordant cases led to a change in clinical management. POCUS guided localization of small bore PICC is a non-invasive and effective alternative to the conventional radiogram. The latter should be recommended when US examination fails to locate the catheter tip.


Systematic Literature Review of the Economic Burden of Celiac Disease.
The prevalence of celiac disease (CD) has rapidly increased over recent decades, but costs related to CD remain poorly quantified. This systematic review assessed the economic burden of CD in North America and Europe. MEDLINE, EMBASE, EconLit, and the Cochrane Library databases were systematically searched to identify English-language literature from 2007 to 2018 that assessed costs, cost effectiveness, and health resource utilization for CD. Forty-nine studies met the inclusion criteria, of which 28 (57.1%) addressed costs of testing and diagnosis; 33 (67.3%) were from Europe. The cost per positive CD diagnosis of testing patients already undergoing esophagogastroduodenoscopy for other indications ranged from 1300 Canadian dollars ($Can) in Canada (2016 value) to €44,712 in the Netherlands (2013 value). Adding the CD test was cost effective when it combined diagnostic modalities (e.g., serology and biopsy). Direct annual excess costs to a US payer per diagnosed CD patient totaled $US6000 (2013 value) more than for a person without CD, chiefly due to outpatient care. Hospitalizations, emergency visits, and medication use were more common with CD. After initiating a gluten-free diet (GFD), patients visited primary care providers less often, used more medications, and missed fewer days from school and work. Most of the few available economic studies of CD assess testing and diagnosis costs, especially in Europe. Methods of testing generally are considered cost effective when they combine diagnostic modalities in symptomatic patients. Most costs to a payer of managing CD derive from outpatient care. Following GFD initiation, patients lose fewer days from work and school than pretreatment.


Preliminary Experience of Viabahn Stent Graft Inside the Occluded Prosthetic Bypass Graft for the Treatment of Above Knee Femoropopliteal Bypass Occlusion.
To describe a multi-center preliminary experience of treating prosthetic above knee femoropopliteal (AKFP) bypass occlusion by placing a Viabahn stent graft inside the occluded prosthetic bypass graft. Retrospective analysis of consecutive 14 patients (mean age 73.2 ± 10.2, 78.6% male) receiving Viabahn stent graft inside the occluded prosthetic bypass graft for the treatment of prosthetic AKFP bypass occlusion in the collaborating hospitals from November 2016 to June 2019 was performed. Technical success was achieved in all patients. Mean lesion length was 34.0 ± 3.5 cm, concomitant thrombectomy or thrombus aspiration was performed in 11 patients (78.6%), and average of 1.57 ± 0.65 Viabahn stent grafts were used. Mean ankle-brachial index improved from 0.24 ± 0.23 to 0.98 ± 0.14 after the treatment. All patients had preoperative ischemic symptoms with 9 patients (64.3%) having Rutherford class > 4 symptoms; however, all preoperative symptoms resolved after the treatment. During the mean follow-up of 450.9 ± 234.7 days, there were two target lesion revascularizations, leading to a primary patency rate of 92.9% and a secondary patency of 100.0% at 1 year. Placing a Viabahn stent graft inside the occluded prosthetic bypass graft for the treatment of prosthetic AKFP bypass occlusion appears to be effective from our preliminary experience. Even though sample size is limited in our study, it may be considered as a potential treatment option before surgical reintervention.


Structural investigation of Klebsiella serotype K70 polysaccharide.
By using the techniques of methylation analysis, uronic acid degradation, partial hydrolysis, and periodate oxidation, th structure of the capsular polysaccharide from Klebsiella serotype K70 has been investigated. Nuclear magnetic resonance was used extensively to characterize fragments obtained as a result of the various degradation procedures. The existence of a linear, hexasaccharide repeating unit having a 1-carboxyethylidene group attached to a 2-linked alpha-L-rhamnosyl residue in every second repeating unit has been demonstrated.


Dynamics of a predator-prey model with generalized Holling type functional response and mutual interference.
Mutual interference and prey refuge are important drivers of predator-prey dynamics. The "exponent" or degree of mutual interference has been under much debate in theoretical ecology. In the present work, we investigate the interplay of the mutual interference exponent, and prey refuge, on the behavior of a predator-prey model with a generalized Holling type functional response - considering in particular the "non-smooth" case. This model can also be used to model an infectious disease where a susceptible population, moves to an infected class, after being infected by the disease. We investigate dynamical properties of the system and derive conditions for the occurrence of saddle-node, transcritical and Hopf-bifurcations. A sufficient condition for finite time extinction of the prey species has also been derived. In addition, we investigate the effect of a prey refuge on the population dynamics of the model and derive conditions such that the prey refuge would yield persistence of the population. We provide additional verification of our analytical results via numerical simulations. Our findings are in accordance with classical experimental results in ecology (Gause, 1934), that show that extinction of predator and prey populations is possible in a finite time period - but that bringing in refuge can effectively yield persistence.


Prediction protein structural classes with pseudo-amino acid composition: approximate entropy and hydrophobicity pattern.
Compared with the conventional amino acid (AA) composition, the pseudo-amino acid (PseAA) composition as originally introduced for protein subcellular location prediction can incorporate much more information of a protein sequence, so as to remarkably enhance the power of using a discrete model to predict various attributes of a protein. In this study, based on the concept of PseAA composition, the approximate entropy and hydrophobicity pattern of a protein sequence are used to characterize the PseAA components. Also, the immune genetic algorithm (IGA) is applied to search the optimal weight factors in generating the PseAA composition. Thus, for a given protein sequence sample, a 27-D (dimensional) PseAA composition is generated as its descriptor. The fuzzy K nearest neighbors (FKNN) classifier is adopted as the prediction engine. The results thus obtained in predicting protein structural classification are quite encouraging, indicating that the current approach may also be used to improve the prediction quality of other protein attributes, or at least can play a complimentary role to the existing methods in the relevant areas. Our algorithm is written in Matlab that is available by contacting the corresponding author.


Establishment of the experimental conditions for inducing saccular cerebral aneurysms in primates with special reference to hypertension.
To find out the optimum experimental conditions for the induction of saccular cerebral aneurysms in primates, various procedures for inducing renal hypertension were used in cynomolgus monkeys treated with ligation of unilateral carotid artery and beta-amino-propionitrile feeding. Animals were divided into four groups. In the first group, both kidneys were simultaneously compressed with a figure-eight ligation. In the second group, the kidneys were ligated at an interval of one week. In the third and fourth groups, posterior branches of both renal arteries were ligated at the same time, or at an interval of one week, respectively. Hypertension about 200 mmHg was produced only in the last group and aneurysms were noted in more than half of these hypertensive animals. The best procedure for renal hypertension to induce cerebral aneurysms was proved to be ligation of the posterior branches of both renal arteries at an interval of one week. We can conclude that lasting severe hypertension is essential for inducing cerebral aneurysms in monkeys.


Financial Impact of Medically Integrated Pharmacy Interventions on Oral Oncolytic Prescriptions.
As the utilization of oral cancer medications rises, it is vital that cancer centers track costs associated with these expensive medications. This research seeks to report the cost interventions associated with medically integrated pharmacies (MIPs) and mail-order pharmacies. Data collection occurred from October 2016 through May 2021. Volunteers input data from their oncology practice into NCODA's Cost Avoidance and Waste Tracker tool, an innovative easy-to use tool that allows practices to document any cost saving interventions or waste occurrences. The Cost Avoidance and Waste Tracker tool was used by nearly 50 MIPs across the country. Specifically, 26 practices submitted cost avoidance data, and 37 practices tracked waste associated with oral oncolytic therapy. Among the 26 practices, 677 cost avoidance events led to a total cost avoidance of $7,057,053.73 US dollars (USD). The net cost avoidance for the MIP's was $6,510,971.28 USD compared with $546,082.45 USD for the external mail-order pharmacies. Among the 37 practices that reported waste, 768 events were reported, leading to a total drug waste of $11,275,642.16 USD. Of that, $8,935,612.15 USD was attributed waste from external mail-order pharmacies, whereas $2,429,592.01 USD worth of drug waste was reported from MIPs. Medically integrated dispensing of oral oncolytic therapies allows for increased pharmacy oversight, leading to increased cost avoidance and reduced waste for patients and third-party payers. Although these data are difficult to compare because of the complexity of workflows at different dispensing sites, the real-world financial differences between medically integrated dispensing and mail-order pharmacies appear to be significant.


Retrospective study of 19 patients with intramedullary spinal cord metastasis.
Intramedullary spinal cord metastasis (ISCM) is a rare but devastating complication of cancer. Due to both widespread MRI availability and longer survival of cancer patients, the probability of discovering an ISCM during the course of the disease has increased and raised issues regarding the management of these patients, and particularly the place of surgery. In this study, we assess predictive factors for surgical outcome and survival. We retrospectively reviewed a series of 19 patients consecutively admitted in our institution from 1993 to 2006 for ISCM, representing the second largest series published in the literature. MRI was performed on all patients. Thirteen underwent microsurgical excision of ISCM. Functional outcome was evaluated and factors influencing survival were statistically analyzed. Median survival was statistically longer when surgery was performed (7.4 vs. 2.6 months). Preoperative neurological status, nature of primary cancer, presence of systemic and/or CNS metastases influenced survival, but differences were without statistical significance. Neurological status improved in 58% (11/19) of operated patients. Optimal management of patients with ISCM is difficult due to the wide variety of clinical situations and the lack of controlled studies on the results of different therapeutic options. Diagnosis should be made as early as possible and surgical resection should be considered as the primary treatment whenever feasible, particularly in the case of rapidly progressive neurological deficits and when a clear cleavage plane exists. Our study shows that surgery could result in both increased survival rate and significant improvement of neurological function.


Preparation and characterization, using high-performance liquid chromatography, of an enzyme forming glucosides of cytokinins.
Cytokinins can occur naturally as glycosides with beta-D-glucose as the sugar substituent. From radish (Raphanus sativus) cotyledons, an enzyme has been partly purified which synthesizes the 7-glucopyranoside of zeatin [6-(4-hydroxy-3-methylbut-trans-2-enylamino)purine], a compound known to occur in this species. High-performance reverse-phase liquid chromatography was uniquely useful as the analytical procedure for quantitative study of the minute amounts of enzyme available. The enzyme uses UDPglucose as the source of the sugar residue. A large number of derivatives of purine are glucosylated, but adenine derivatives with an alkyl side chain at least three carbon atoms in length at position N6 are preferentially glucosylated. This corresponds to the structural features required for high cytokinin activity. The 7-glucoside of zeatin is known to be very weakly active in cytokinin bioassays. Hence, this enzyme, and others catalyzing the same reaction, have a role in the regulation of cytokinin activity.


Special Issue: Synthesis and Characterization of Graphene-Based Hybrid Nanostructures.
Graphene has numerous outstanding physical properties such as excellent electron mobility, extremely high thermal conductivity, high flexibility, remarkable mechanical strength, and high transparency [...].


Mireval: a web tool for simple microRNA prediction in genome sequences.
We have developed an online tool called mirEval which can search sequences of up to 10 000 nt for novel microRNAs in multiple organisms. It is a comprehensive tool, easy to use and very informative. It will allow users with no prior knowledge of in-silico detection of microRNAs to take advantage of the most successful approaches to investigate sequences of interest. The mirEval web server is available at http://tagc.univ-mrs.fr/mireval


Stress reactivity and its effects on subsequent food intake in depressed and healthy women with and without adverse childhood experiences.
Adverse childhood experiences (ACE) increase the risk to develop major depressive disorder (MDD) and obesity or metabolic syndrome in adulthood. In addition, ACE may be associated with an exaggerated endocrine response to stress, which, in turn, may lead to enhanced food intake resulting in obesity and metabolic problems. We systematically examined the stress response and consecutive food intake in 32 women with MDD and ACE as determined by a clinical interview (Early Trauma Inventory), 52 women with MDD without ACE, 22 women with ACE but no current or lifetime MDD and 37 healthy women without either MDD or ACE. All participants underwent a psychosocial stress test (Trier Social Stress Test, TSST) and a control condition (Placebo-TSST) before they were offered a buffet of snacks. Participants were not aware that the primary outcome variable was the amount of consumed kilocalories (kcal). The four groups did not differ in demographic variables. Stress resulted in higher cortisol release and higher blood pressure compared to the control condition. Patients with MDD without ACE had a significantly lower cortisol response to stress compared to controls. Across groups, we found higher kcal intake after stress compared to the control condition. Comparing high and low cortisol responders to stress, higher kcal intake after stress was only seen in those with low cortisol release. This study provides evidence that blunted rather than enhanced cortisol release to stress might lead to increased food intake, independent from MDD and ACE.


Adriamycin cardiotoxicity: endomyocardial biopsy evidence of enhancement by irradiation.
Endomyocardial biopsies were examined in 12 patients receiving total doses of Adriamycin from 90 to 445 mg/M2. These patients had also received previous mediastinal irradiation (from less than 600 to 5700 rad) over periods varying from 6 months to 14 years prior to the endomyocardial biopsy. Severity of pathological change in these 12 patients was compared with that of dose-matched control patients who had not received mediastinal radiation. The severity of the histopathologic changes was scored on a scale from 0 (normal) to 3 (marked abnormality). The mean score of the group receiving irradiation (2.0 +/- 0.89) was significantly higher than the score in those not irradiated (1.18 +/- 0.23) (p less than 0.001). Morphological demonstration of a "recall phenomenon" of latent radiation changes by Adriamycin was demonstrated in small intramyocardial vessels. This study indicates that radiation, even if remote, enhances Adriamycin-induced cardiomyopathy. Therefore, Adriamycin must be given cautiously in patients who have received previous mediastinal radiotherapy.


[Use of a TLC method for the simultaneous determination of an enzyme complex of nucleic acid metabolism during the isolation of polynucleotide phosphorylase].
For the simultaneous determining of several enzymes of nucleic acid metabolism during polynucleotide phosphorylase isolation TLC was used. It was found that using TLC one can simultaneously detect six and more enzymes, e. g. polynucleotide phosphorylase, 5'-nucleotidase, exoribonuclease together with nucleosidediphosphatase, desaminase etc. The method is simple and accessible.


Conduction system in two cases of sudden death two years after the Mustard procedure.
This report describes a serial section examination of the conduction system in two children who died suddenly 2 years following the Mustard procedure for complete transposition. The first child manifested sinus rhythm alternating with junctional rhythm in the last year of life. The second child, 2 months before death, had first-degree atrioventricular (AV) block which progressed to second-degree block with 2:1 conduction alternating with a junctional rhythm with AV dissociation. Examination of the conduction system in both cases revealed the approaches to the sinoatrial (SA) and the AV nodes to be markedly fibrosed. In addition, in Case 1 the SA node was interrupted by sutures and in Case 2 the SA node was considerably fibrosed. The arrhythmias produced and the probable cause of sudden death in both cases may be related to surgical injury to the approaches to the SA and AV nodes. This study and the review of the literature emphasize the necessity of maintaining the integrity of the SA node, the approaches to the SA and AV nodes, and the superior preferential pathway while performing the Mustard procedure for complete transposition.


Housing environment and mental health of Europeans during the COVID-19 pandemic: a cross-country comparison.
Many studies have investigated the impact of the COVID-19 pandemic on mental health. Throughout the pandemic, time spent at home increased to a great extent due to restrictive measures. Here we set out to investigate the relationship between housing conditions and the mental health of populations across European countries. We analyzed survey data collected during spring 2020 from 69,136 individuals from four cohorts from Denmark, France, and the UK. The investigated housing conditions included household density, composition, and crowding, access to outdoor facilities, dwelling type, and urbanicity. The outcomes were loneliness, anxiety, and life satisfaction. Logistic regression models were used, and results were pooled using random-effects meta-analysis. In the meta-analysis, living alone was associated with higher levels of loneliness (OR = 3.08, 95% CI 1.87-5.07), and lower life satisfaction (OR = 1.27, 95% CI 1.05-0.55), compared to living with others. Not having access to an outdoor space and household crowding were suggestively associated with worse outcomes. Living in crowded households, living alone, or lacking access to outdoor facilities may be particularly important in contributing to poor mental health during a lockdown. Addressing the observed fundamental issues related to housing conditions within society will likely have positive effects in reducing social inequalities, as well as improving preparedness for future pandemics.


Holocene climate change in southern Oman deciphered by speleothem records and climate model simulations.
Qunf Cave oxygen isotope (δ18Oc) record from southern Oman is one of the most significant of few Holocene Indian summer monsoon cave records. However, the interpretation of the Qunf δ18Oc remains in dispute. Here we provide a multi-proxy record from Qunf Cave and climate model simulations to reconstruct the Holocene local and regional hydroclimate changes. The results indicate that besides the Indian summer monsoon, the North African summer monsoon also contributes water vapor to southern Oman during the early to middle Holocene. In principle, Qunf δ18Oc values reflect integrated oxygen-isotope fractionations over a broad moisture transport swath from moisture sources to the cave site, rather than local precipitation amount alone, and thus the Qunf δ18Oc record characterizes primary changes in the Afro-Asian monsoon regime across the Holocene. In contrast, local climate proxies appear to suggest an overall slightly increased or unchanged wetness over the Holocene at the cave site.


Potential regulation by miRNAs on glucose metabolism in liver of common carp (Cyprinus carpio) at different temperatures.
Water temperature can affect the metabolism of fish. Common carp (Cyprinus carpio) is a representative eurythermic fish that can survive at a wide range of ambient temperatures, allowing it to live in an extensive geographical range. The goal of this work was to study the glucose metabolism of common carp at different temperatures and determine the miRNAs involved in the regulation of glucose metabolism. We determined the indicators related to glucose metabolism after long-term temperature stress and constructed nine small RNA libraries of livers under different temperature stress (5 °C, 17 °C, and 30 °C, with three biological replicates for each temperature), and subjected these samples to high-throughput sequencing. A positive relationship was observed between weight gain rate (WGR) and temperature increase after 18 days of temperature stress. However, the glucose level in the plasma maintained a gentle decrease. Unexpectedly, liver lactic acid levels were elevated in HTG (high temperature group) and LTG (low temperature group). Six down-regulated miRNAs (miR-122, miR-30b, miR-15b-5p, miR-20a-5p, miR-1, and miR-7b) were identified as involved in the regulation of glycolysis. Twelve genes were predicted as targets of these miRNAs, and these genes are in pathways related to pyruvate metabolism, glycolysis/gluconeogenesis, and the citrate cycle (TCA cycle). The results allowed prediction of a potential regulatory network of miRNAs involved in the regulation of glycolysis. The target genes of six down-regulated miRNAs were up-regulated under temperature stress, including Aldolase C, fructose-bisphosphate, b (ALDOCB), multiple inositol-polyphosphate phosphatase 1 (MINPP1), phosphoenolpyruvate carboxykinase 1 (PCK1), pyruvate dehydrogenase E1 alpha 1 (PDHA1), aldehyde dehydrogenase 9 family member A1a (ALDH9A1A), Acetyl-coenzyme A synthetase (ACSS), lactate dehydrogenase b (LDH-b), and glyoxylate reductase/hydroxypyruvate reductase (GRHPR). Other key genes of glycolysis, glucose transporter 1 (GLUT-1), pyruvate kinase PKM (PKM), and mitochondrial pyruvate carrier (MPC) were significantly up-regulated in LTG and HTG. Overall, the results suggest that miRNAs maintain their energy requirements by regulating glycolysis and play an important role in the molecular response to cold and heat stress of common carp. These data provide the foundation for further studies of the role of miRNAs in environmental adaptation in fish.


Genome-wide analysis of PmTCP4 transcription factor binding sites by ChIP-Seq during pistil abortion in Japanese apricot.
The TCP4 transcription factor plays an important role in plant growth and development, especially in flower development. PmTCP4 is involved in the process of pistil abortion in Japanese apricot, but its molecular mechanism, particularly the DNA binding sites and co-regulatory genes, are quite unknown. Therefore, to identify the genome-wide binding sites of PmTCP4 transcription factors and their co-regulatory genes, chromatin immunoprecipitation sequencing (ChIP-Seq) was carried out. ChIP-Seq data produced the maximum enriched peaks in two Japanese apricot cultivars 'Daqiandi' (DQD) and 'Longyan' (LY), which showed that the majority of DNA-protein interactions are relevant and have a significant function in binding sites. Moreover, 720 and 251 peak-associated genes regulated by PmTCP4 were identified in DQD and LY, respectively, and most of them were involved in the flower and pistil development process. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that photosynthesis and oxidative phosphorylation were the most enriched pathways in both cultivars and all identified genes related to these pathways were down-regulated. This study will provide a reference for a better understanding of the PmTCP4 regulatory mechanism during pistil abortion in Japanese apricot.


Deep learning-based PM2.5 prediction considering the spatiotemporal correlations: A case study of Beijing, China.
Air pollution is one of the serious environmental problems that humankind faces and also a hot topic in Northeastern Asia. Therefore, the accurate prediction of PM2.5 (particulate matter with an aerodynamic diameter of ≤2.5 μm) is very significant in the management of human health and the decision-making of government for the environmental management. In this study, a spatiotemporal convolutional neural network (CNN) and long short-term (LSTM) memory (CNN-LSTM) model (also called PM (particulate matter) predictor) was proposed and used to predict the next day's daily average PM2.5 concentration in Beijing City. The spatiotemporal correlation analysis using the mutual information (MI) was performed, considering not only the linear correlation but also nonlinear correlation between target and observation parameters; in addition, it was fully considered for the whole area of China with the target monitoring station as the center and also for the historic air quality and meteorological data. As a result, the spatiotemporal feature vector (STFV) which reflects both linear and nonlinear correlations between parameters was effectively constructed. The PM predictor secured a fast and accurate prediction performance by efficiently extracting the inherent features of the latent air quality and meteorological input data associated with PM2.5 through CNN and by fully reflecting the long-term historic process of input time series data through LSTM. The air quality and meteorological data from the 384 monitoring stations which represents the whole area of China with Beijing City as the center during the 3 years (Jan. 1st, 2015 to Dec. 31th, 2017) were used to verify the validity of the proposed method. In conclusion, the proposed method was proved to have a better stability and prediction performance compared to multi-layer perceptron (MLP) and LSTM models.


Brainstem abscess.
A case of midbrain abscess that was successfully treated by surgical evacuation is reported. The abscess was located in the rostral tegmentum of the midbrain and was aspirated using an infratentorial supracerebellar approach. The patient subsequently returned to his high school. Early accurate diagnosis and appropriate surgical management are especially important for successful treatment of this previously fatal condition.


Assessment of the quality and frequency of mutations occurrence in PTEN gene in endometrial carcinomas and hyperplasias.
The quality and frequency of mutations in PTEN gene were assessed in 59 carcinomas and 6 hyperplasias of the endometrium in women. Screening for mutations was done in all exons of PTEN gene by the PCR-SSCP analysis and DNA sequencing. Results were correlated with histological status and clinical features of endometrial carcinomas. In 45.8% (27/59) of carcinomas, 36 somatic mutations were detected in PTEN gene. In seven carcinomas, two mutations and in one carcinoma three mutations coexisted simultaneously. Moreover in 33.3% (2/6) of hyperplasia cases mutations were shown. Most identified mutations (57.9%) were present in exons 5 and 8, less frequently in exons 2 (15.8%) and 7 (13.2%) and they were least frequent in exons 1 and 3 (5.3% each). No mutations were found in exons 4, 6 and 9. Of all identified mutations, 73.7% of those resulting in truncated protein were present due to deletions, insertions and nonsense mutations. Missense mutations accounted for 13.2% of mutations and they were present only in exon 5. One point mutation (2.5%) was in intronic splice site. The remaining 10.5% of mutations were neutral polymorphisms. No statistically significant correlation were found between the frequency of PTEN gene mutations and the clinical stage of endometrial carcinomas. However, evident statistically significant, reverse correlation were observed between the frequency of mutations and the grade of morphological differentiation of the diseases (chi(2)=7.2393, alpha=0.0071). In conclusion, our data support the view that PTEN gene mutations are frequent events involved in development of endometrial carcinomas in women.


Risks and mechanisms of cardiovascular events in users of oral contraceptives.
Three large British studies on the vascular effects of oral contraceptives have established that the risk of thromboembolic episodes, both venous and arterial, rises with increasing estrogen dose. Two of these studies have also demonstrated a dose-dependent relationship between the progestogenic component of oral contraceptives and the risk of arterial disease, though not of venous events. In men, high levels of factor VII coagulant activity, VIIC, and plasma fibrinogen are associated with an increased risk for ischemic heart disease. In view of the dose-dependent relationship between estrogen and these two clotting factors, especially VIIC, it is likely that the effects of oral contraceptive usage on the risk for thromboembolism are mediated substantially through the level of coagulability. The relationship between the progestogenic component of oral contraceptives and the risk for arterial disease is probably related, at least in part, to the effects of progestogens on blood pressure.


Methanogenesis under acidic pH conditions in a semi-continuous reactor system.
Operating an anaerobic digester at low pH could offer several advantages over operation at neutral pH. Most wastewater streams targeted for anaerobic digestion are inherently acidic, requiring alkalinity supplementation (at added expense) to buffer the pH at neutral. Additionally, previously published work completed by the authors using batch systems suggested that lowering the system pH could increase methane production by as much as 30%. The goal of this research was to evaluate the feasibility of sustaining methanogenesis at low pH in a semi-continuous laboratory-scale fermentor. Significant methane production was achieved in a system ranging in pH from approximately 4.0-5.3. Results show that, if the consortium is allowed to sufficiently acclimate to acidic conditions, methanogenesis can be maintained under acidic pH conditions, resulting in overall chemical oxygen demand (COD) reduction and methane production comparable to that achieved in a neutral pH system.


Comparison of long-term survival outcome after curative hepatectomy between selected patients with non-colorectal and colorectal liver metastasis: A propensity score matching analysis.
Liver resection is an established treatment of choice for colorectal liver metastasis (CLM). However, the role of hepatectomy for non-colorectal liver metastasis (NCLM) is less clear. From 2004 to 2017, 264 patients received curative hepatectomy for NCLM (n = 28) and CLM (n = 236). Propensity score (PS) matching was performed between two groups, with respect to the significant confounding factors. Short-term and long-term outcomes were compared between PS matched groups. Univariate analysis was performed to identify prognostic factors affecting overall and recurrence-free survival. After PS matching, there were 28 patients in NCLM group and 56 patients in CLM group. With a median follow-up of 34 months, there was no significant difference in 5-year overall survival rate between NCLM and CLM groups (62% vs. 39%) (P = 0.370). The 5-year recurrence-free survival rate was also comparable between NCLM and CLM groups (23% vs. 22%) (P = 0.707). Use of pre-operative systemic therapy (hazard ratio: 2.335, CI 1.157-4.712), multifocal tumors (hazard ratio: 1.777, CI 1.010-3.127), tumor size (hazard ratio: 1.135, CI 1.012-1.273), R1 resection (hazard ratio: 2.484, CI 1.194-5.169) and severe complications (hazard ratio: 6.507, CI 1.454-29.124), but not tumor type (NCLM vs. CLM), were associated with poor overall survival. Hepatectomy for NCLM can achieve similar oncological outcomes in selected patients as those with CLM. Significant prognostic factors were identified associating with worse overall survival.


Bis[(4-methyl-phen-yl)di-phenyl-phosphine-κP](nitrito-κ2 O,O')silver(I).
The title AgI complex, [Ag(NO2)(C19H17P)2], reveals a distorted pseudo-trigonal-planar shape around the AgI atom geometry resulting from the coordination of two phosphine ligands, as well as a nitrito-O,O' ligand coordinating to the silver(I) atom through the oxygen atoms; in this description, the two oxygen atoms are assumed to occupy one position, forming an acute O-Ag-O angle of 51.44 (9)°. The plane resulting from the NO2 coordination to Ag is nearly perpendicular to the plane from the coordination of the phosphine-P atoms to Ag [dihedral angle = 86.43 (9)°].


Intraoperative burst suppression is associated with postoperative delirium following cardiac surgery: a prospective, observational study.
Postoperative delirium (POD) occurs frequently after cardiac surgery and is associated with increased morbidity and mortality. We analysed whether perioperative bilateral BIS monitoring may detect abnormalities before the onset of POD in cardiac surgery patients. In a prospective observational study, 81 patients undergoing cardiac surgery were included. Bilateral Bispectral Index (BIS)-monitoring was applied during the pre-, intra- and postoperative period, and BIS, EEG Asymmetry (ASYM), and Burst Suppression Ratio (BSR) were recorded. POD was diagnosed according to the Confusion Assessment Method for the Intensive Care Unit, and patients were divided into a delirium and non-delirium group. POD was detected in 26 patients (32%). A trend towards a lower ASYM was observed in the delirium group as compared to the non-delirium group on the preoperative day (ASYM = 48.2 ± 3.6% versus 50.0 ± 4.7%, mean ± sd, p = 0.087) as well as before induction of anaesthesia, with oral midazolam anxiolysis (median ASYM = 49.5%, IQR [47.4;51.5] versus 50.6%, IQR [49.1;54.2], p = 0.081). Delirious patients remained significantly (p = 0.018) longer in a burst suppression state intraoperatively (107 minutes, IQR [47;170] versus 44 minutes, IQR [11;120]) than non-delirious patients. Receiver operating analysis revealed burst suppression duration (area under the curve = 0.73, p = 0.001) and BSR (AUC = 0.68, p = 0.009) as predictors of POD. Intraoperative assessment of BSR may identify patients at risk of POD and should be investigated in further studies. So far it remains unknown whether there is a causal relationship or rather an association between intraoperative burst suppression and the development of POD. clinicaltrials.gov NCT01048775.


World survey on the complications of hepatic and prostate cryotherapy.
Cryotherapy is used as a treatment for nonresectable liver tumors and adenocarcinoma of the prostate. Morbidity and mortality following cryotherapy are generally considered to be infrequent, but a syndrome of multiorgan failure, severe coagulopathy, and disseminated intravascular coagulation following hepatic cryotherapy has been described and referred to as the cryoshock phenomenon. In this study we aimed to assess and describe the incidence and clinical features of the cryoshock phenomenon following cryosurgery from the surveyed experience of a large number of clinical centers and to relate the data to the overall mortality and morbidity of this treatment. A questionnaire was sent to all cryotherapy users (n = 299) of whom we were aware. We requested information on the number of patients treated, the occurrence, and the clinical features of cryoshock and mortality and morbidity following cryotherapy of the prostate or liver. Altogether 134 completed questionnaires were returned (44.8%). Seventy-two centers had experience with hepatic cryotherapy and 62 with prostate cryotherapy. Following hepatic cryotherapy, the phenomenon of cryoshock was observed in 21 of 2173 patients (1%) and was responsible for 6 of 33 perioperative deaths (18.2%). Cryoshock was rare following prostate cryotherapy (2 of 5432 patients, 0.04%) and did not contribute to the overall mortality of 0.06%. Hepatic and prostate cryotherapy are safe. Cryoshock is rare after prostate cryotherapy but occurs in 1% of patients following hepatic cryotherapy. Cryoshock is associated with a high risk of death, being responsible for 18.2% of deaths in this survey. Research regarding the mechanism and possible avoidance of cryoshock is required.


Accidental intra-arterial injection.
The potential for an accidental intra-arterial injection is present whenever an intravenous route of drug administration is used. Because of the serious nature of the morbidity associated with this iatrogenic injury, and its preventability, this article is presented to update the available information on the etiology, diagnosis, treatment, and prevention of this problem.


Health-related behavior and adolescent mothers.
To explore health-related behaviors among adolescent mothers living in the rural area of Taoyuan, Taiwan. A cross-sectional descriptive design and nonrandom survey method were used. The sample consisted of 37 adolescent mothers, identified by public health nurses. Standardized interview and Adolescent Health Promotion (AHP) questionnaire. Findings revealed a pattern of economic disadvantage. Nearly half of the participants still lived with their biological parents. Two-thirds needed economic support from their parents (generally coming from their biological mother). Thirty-five percent of participants reported never using contraceptives, two-thirds had never had a Pap smear, and 44% did not breast-feed their infants. Nearly 60% of the children were cared for by the biological mothers of the participants. Adolescent mothers with high school education, and who were employed, married, and received parental economic support had better health-related behaviors than adolescent mothers without these characteristics. Although the study sample has geographic limitations, future international studies with similar populations of adolescent mothers in rural settings will help public health nurses understand adolescent mothers' stressors and needs which in turn affect their health-related behaviors. Intervention strategies are needed to encourage behaviors to keep this population healthy.


Unusual presentation of a giant jejunal gastrointestinal stromal tumor.
Gastrointestinal stromal tumours (GISTs) are rare tumours. Tumour rupture is an additional adverse prognostic factor and should be recorded, regardless of whether it took place before or during surgery. A case report of hemoperitoneum from spontaneous rupture of a gastrointestinal stromal tumor of the jejunum is presented. The patient underwent an urgent laparotomy. An "en bloc" resection was performed. The information in the literature is examined. Spontaneous rupture of the tumor with concomitant hemoperitoneum is an important prognostic factor in these patients. The hemoperitoneum contributes to a worse prognosis because of its ability to produce peritoneal seeding KEY WORDS: Gist.


Subcellular localization of 14-3-3 proteins in Toxoplasma gondii tachyzoites and evidence for a lipid raft-associated form.
A polyclonal antibody was raised against a Toxoplasma gondii 14-3-3-gluthatione S-transferase fusion protein obtained by cloning a 14-3-3 cDNA sequence determined from the T. gondii database. This antibody specifically recognized T. gondii 14-3-3 without any cross-reaction with mammalian proteins. Immunofluorescence microscopy studies of the tachyzoites or the T. gondii-infected cells suggested cytosolic and membranous localizations of 14-3-3 protein. Different subcellular fractions were prepared for electrophoresis analysis and immunodetection. 14-3-3 proteins were found in the cytosol, the membrane fraction and Triton X-100-resistant membranes. Two 14-3-3 isoforms were detected. The major one was mainly cytoplasmic and to a lesser extent membrane-associated, whereas the minor isoform was associated with the detergent-resistant lipid rafts.


Objects that make objects: the population dynamics of structural complexity.
To analyse the evolutionary emergence of structural complexity in physical processes, we introduce a general, but tractable, model of objects that interact to produce new objects. Since the objects--epsilon-machines--have well-defined structural properties, we demonstrate that complexity in the resulting population dynamical system emerges on several distinct organizational scales during evolution--from individuals to nested levels of mutually self-sustaining interaction. The evolution to increased organization is dominated by the spontaneous creation of structural hierarchies and this, in turn, is facilitated by the innovation and maintenance of relatively low-complexity, but general individuals.


Assessment of regional timing of left ventricular systolic longitudinal movement by Doppler tissue synchronization imaging in structurally normal hearts.
To study the feasibility of a new semiautomatic echocardiographic modality called Tissue Synchronization Imaging (TSI) for measurement of the longitudinal left ventricular (LV) movement. TSI was used in 20 subjects with structurally normal hearts to measure the time aspect of the regional longitudinal LV systolic movement in the apical four chamber view. Inter- and intraobserver agreement and the beat to beat variation were tested and compared to previously manually measured peak systolic delay (PSD) between the interventricular septum (IS) and the lateral free wall (LFW) at basal and mid LV, respectively (n=19). TSI showed acceptable reproducibility and close correlation to manually measured PSD. The TSI method did not show false synchronous regional LV movement when synchrony was defined as a PSD<+/-25 ms. After minor adjustment of the TSI interval, 76.9% of the synchronous LV patterns in basal LV were correctly classified as compared to manual measurements. The TSI method is accurate for clinical screening to reveal synchrony. At the present development the TSI method is not accurate enough to quantify regional systolic LV asynchrony, and still manual measurement of PSD is mandatory.


The development of vaccines: how the past led to the future.
The history of vaccine development has seen many accomplishments, but there are still many diseases that are difficult to target, and new technologies are being brought to bear on them. Past successes have been largely due to elicitation of protective antibodies based on predictions made from the study of animal models, natural infections and seroepidemiology. Those predictions have often been correct, as indicated by the decline of many infections for which vaccines have been made over the past 200 years.


Umbilical Cord Blood-Derived Exosomes in Maternal-Fetal Disease: a Review.
The nutrients and other factors transported by umbilical cord blood, which is vital for fetal survival, play crucial roles in fetal development. There are various communication modes between the fetal-placental system and the maternal-placental system, and these communication modes are all mediated by umbilical cord blood. During the process of umbilical cord blood transportation, the changes of some nutrients and factors may play a key role in fetal development. Exosomes, which are members of the extracellular vesicle family, are present in the umbilical cord blood and play roles in information transmission as a result of their efficient cellular communication activity. The study of umbilical cord blood-derived exosomes provides a new approach for research on the etiology of maternal-fetal diseases and they may be useful for the development of intrauterine treatments. This review summarizes specific functions and research directions regarding umbilical cord blood-derived exosomes, and their potential associations with pregnancy complications.


Abstract concepts require concrete models: why cognitive scientists have not yet embraced nonlinearly coupled, dynamical, self-organized critical, synergistic, scale-free, exquisitely context-sensitive, interaction-dominant, multifractal, interdependent brain-body-niche systems.
After more than 15 years of study, the 1/f noise or complex-systems approach to cognitive science has delivered promises of progress, colorful verbiage, and statistical analyses of phenomena whose relevance for cognition remains unclear. What the complex-systems approach has arguably failed to deliver are concrete insights about how people perceive, think, decide, and act. Without formal models that implement the proposed abstract concepts, the complex-systems approach to cognitive science runs the danger of becoming a philosophical exercise in futility. The complex-systems approach can be informative and innovative, but only if it is implemented as a formal model that allows concrete prediction, falsification, and comparison against more traditional approaches.


Relationship between substance P, intestinal wall compliance and vascular resistance in the canine ileum.
Substance P (SP) is one of many vasoactive peptides found within the gastrointestinal tract with actions on intestinal smooth muscle. Thus, its vasodilatory action could be attenuated through its stimulatory effect on intestinal smooth muscle producing subsequent elevations in extravascular pressure and thus, passively opposing the vasodilation. The aim of this study was to examine for such a possibility for SP by simultaneously assessing ileal perfusion pressure and intestinal wall compliance in the canine ileum during intra-arterial infusion of SP. Infusion of SP at either 0.74 or 7.4 pmol/min significantly decreased ileal perfusion pressure by 8 and 30%, respectively, without affecting wall compliance. During SP infusion at 74 pmol/min, perfusion pressure fell by 49% while wall compliance decreased by 43%, reflecting a significant increase in ileal wall tension. During SP infusion at 7.4 and 74 pmol/min, a 'two-phase' reduction in perfusion pressure was observed. These data suggest that although SP markedly increases ileal wall tension, the elevation in extravascular pressure produced is not strong enough to overcome its potent vasodilatory action in the canine ileum. The potential of a physiologic role for blood-borne SP is discussed.


A phase-III study of recombinant interleukin 2 and 5-fluorouracil chemotherapy in patients with metastatic colorectal cancer.
Sixteen patients with metastatic colorectal cancer have been treated with a regimen involving an 120 h continuous infusion of rIL-2, 18 x 10(6) iu m-2 day followed by three injections of 5FU 600 mg m-2 at weekly intervals. Entry criteria included no previous chemotherapy, ambulatory performance status, and a measurable lesion. In most cases side effects were easily manageable and only one patient required transfer to an intensive care unit with the capillary leak syndrome. In three patients persistent hypotension was found to be unrelated to treatment with rIL-2, being caused respectively by a line infection, pulmonary embolus, and bowel perforation. This last proved a fatal complication. Five patients (33%; [95% confidence limits, 11.8%-61.6%]) achieved a partial response, and two non-responders later achieved a partial response when treated with weekly 5FU. This regimen is currently being evaluated in a phase-III randomised controlled trial.


Port wine stain treatment with a dual-wavelength Nd:Yag laser and cryogen spray cooling: a pilot study.
We report on a pilot study of port wine stain (PWS) treatment with a prototype Nd:YAG/KTP laser system, emitting simultaneously at 1,064 and 532 nm, and equipped with a cryogen spray cooling (CSC) device. On 10 patients (4-36 years old, mean: 16.2 years) with skin types II-III, therapeutic efficacy of the dual-wavelength laser (KTP+) was compared with a standard KTP laser (532 nm only) at the same pulse duration (25 millisecond), spot diameter (3 mm), and CSC parameters. The fluences were selected in order to obtain the same immediate response with both laser systems. Blanching of each test segment was assessed 8 weeks post treatment by an independent evaluator and by the subjects, and graded on a 1-4 scale. Significant blanching of PWS was noted 8 weeks after a single therapeutic session with the KTP+ laser (mean: 532 nm radiant exposure: 8.2 J/cm(2)), very similar to that observed with KTP at 12.4 J/cm(2). The evaluator noticed a slight brownish coloration in areas treated with the KTP+ laser. Isolated beam-sized atrophic scars were present in two patients where KTP+ (9 and 10 J/cm(2)) and KTP (14 J/cm(2)) lasers were used. The addition of 1,064 nm radiation allowed a significant reduction of 532 nm radiant exposure with no loss of efficacy in PWS treatment.