Tidal heat pulses on a reef trigger a fine-tuned transcriptional response in corals to maintain homeostasis.
For reef-building corals, extreme stress exposure can result in loss of endosymbionts, leaving colonies bleached. However, corals in some habitats are commonly exposed to natural cycles of sub-bleaching stress, often leading to higher stress tolerance. We monitored transcription in the tabletop coral Acropora hyacinthus daily for 17 days over a strong tidal cycle that included extreme temperature spikes, and show that increases in temperature above 30.5°C triggered a strong transcriptional response. The transcriptomic time series data allowed us to identify a set of genes with coordinated expression that were activated only on days with strong tides, high temperature, and large diel pH and oxygen changes. The responsive genes are enriched for gene products essential to the unfolded protein response, an ancient cellular response to endoplasmic reticulum stress. After the temporary heat pulses passed, expression of these genes immediately decreased, suggesting that homeostasis was restored to the endoplasmic reticulum. In a laboratory temperature stress experiment, we found that the expression of these environmentally responsive genes increased as corals bleached, showing that the unfolded protein response becomes more intense during more severe stress. Our results point to the unfolded protein response as a first line of defense that acroporid corals use when coping with environmental stress on the reef, thus enhancing our understanding of coral stress physiology during a time of major concern for reefs.


High-throughput genotyping of copy number variation in glutathione S-transferases M1 and T1 using real-time PCR in 20,687 individuals.
Characteristic for the genes encoding glutathione S-transferase (GST) M1 and GSTT1 is a null allele, suggested to increase susceptibility to chronic diseases. We report an optimized method for the determination of copy number variation (CNV) in GST genes. Real-time multiplex PCR reactions were optimized for quantification of GSTM1 and GSTT1 CNV using the DeltaCt method, a fixed volume of diluted DNA, a total volume of 10 microL, 384-well formats, and single determinations of each sample. Consistent genotyping was obtained using DNA in a range of 0.41 ng to 100 ng. In a general population sample of 20,687 individuals the genotype frequencies were concordant with other methods used as standards. Throughput was 4600 genotypes per day at a reagent price of 0.5 euros per sample. This high-throughput, low cost method accurately determines CNV in the GST genes enabling reliable estimates of disease prediction in large epidemiological samples.


Unusual association of Axenfeld-Rieger syndrome and wandering spleen: A case report.
Axenfeld-Rieger syndrome (ARS) is an autosomal dominant genetic disease characterized by ocular developmental disorders and its association with torsion of wandering spleen (WS) has not been reported to date to the best of our knowledge. This study aimed to describe a rare case of ARS observed at our emergency department. A 25-year-old female presented with a constant lower abdominal pain of increasing severity. Diagnostic computed tomography with intravenous contrast material showed a non-homogenously enhanced splenic parenchyma with a twisted vascular pedicle. Further, an emergent laparoscopic exploration was performed, and an ischemic spleen without its normal ligamentous attachments was noted. Notably, the spleen did not regain its normal vascularity after detorsion; thus, we performed the laparoscopic total splenectomy. The postoperative course was uneventful, and the patient was discharged on the 5th postoperative day. This case demonstrates a rare association of WS and ARS. Early diagnosis of WS in the emergency department is important to prevent pedicle torsion or splenic necrosis and to avoid splenectomy.


[Course observations of hypertrophic obstructive myocardiopathy].
The course of HOCM is characterized by a slow progression. Symptoms can often be influenced favourably by medical treatment. Altogether there is some difference between the course of untreated and the propranolol-treated patient groups which is, however, not statistically significant. Furthermore, the rate of sudden death is uninfluenced. Comparing clinical and haemodynamic results in medicically treated patients we find a reduction of the outflow tract obstruction in case with clinical improvement but not a reduction of the enddiastolic pressure. Independent on the clinical course there was a significant increase of the enddiastolic pressure after 5.5 years. We may conclude that there is a progredient process of hypertrophy which is uninfluenced by the obstruction and by conservative management. The best results are obtained in the operated group. According to our results a surgical intervention should possibly be considereed more generously.


Type 5 phosphodiesterase expression is a critical determinant of the endothelial cell angiogenic phenotype.
Type 5 phosphodiesterase (PDE5) inhibitors increase endothelial cell cGMP and promote angiogenesis. However, not all endothelial cell phenotypes express PDE5. Indeed, whereas conduit endothelial cells express PDE5, microvascular endothelial cells do not express this enzyme, and they are rapidly angiogenic. These findings bring into question whether PDE5 activity is a critical determinant of the endothelial cell angiogenic potential. To address this question, human full-length PDE5A1 was stably expressed in pulmonary microvascular endothelial cells. hPDE5A1 expression reduced the basal and atrial natriuretic peptide (ANP)-stimulated cGMP concentrations in these cells. hPDE5A1-expressing cells displayed attenuated network formation on Matrigel in vitro and also produced fewer blood vessels in Matrigel plug assays in vivo; the inhibitory actions of hPDE5A1 were reversed using sildenafil. To examine whether endogenous PDE5 activity suppresses endothelial cell angiogenic potential, small interfering RNA (siRNA) constructs were stably expressed in pulmonary artery endothelial cells. siRNA selectively decreased PDE5 expression and increased basal and ANP-stimulated cGMP concentrations in these conduit cells. PDE5 downregulation increased network formation on Matrigel in vitro and increased blood vessel formation in Matrigel plug assays in vivo. Collectively, our results indicate that PDE5 activity is an essential determinant of angiogenesis and suggest that PDE5 downregulation in microvascular endothelium imparts a stable, enhanced angiogenic potential to this cell type.


Peripartum cardiomyopathy, what if your patient plans to reconceive?
Patients with peripartum cardiomyopathy (PPCM) often express a desire to conceive again, and the risk of relapse in future pregnancies should be disclosed. No consensus is available that can determine that risk. Adequate contractile reserve, evidenced by a stress echocardiogram (exercise or dobutamine), can identify those with lower relapse risk.


A simple source of fluorescent x rays for the study of radiographic imaging systems.
The properties of a simple source of fluorescent x rays were investigated with regard to its suitability for the study of radiographic imaging systems. The source, consisting of a diagnostic x-ray tube, fluorescent targets, and filters, was found to yield highly monoenergetic x-ray fluxes with intensity sufficient to allow the speed of medium- and high-speed screen-film systems to be studied as a function of x-ray energy.


Assessment of Cardiac Autonomic Tone Following Long Sudarshan Kriya Yoga in Art of Living Practitioners.
The breathing processes are known to modulate cardiac autonomic tone and improve psychological status. We investigated cardiac autonomic tone following long Sudarshan Kriya Yoga (SKY) using heart rate variability (HRV) and skin conductance level (SCL). Thirty healthy volunteers (age 28.3 ± 8.4 years; 23 M: 7 F) participated in the study. Electrocardiogram (ECG) and SCL were recorded for 5 min each, before and after long SKY. Long SKY is a combination of pranayama and cyclic rhythmic breathing and is performed by following the guided audio instructions. HRV analysis was used for the assessment of cardiac autonomic tone. Time and frequency domain parameters of HRV were calculated by using RR interval of ECG. SCL was acquired using Galvanic skin response (GSR) amplifier of PowerLab in microSeimens (μS). Time domain parameters of HRV, including mean RR interval (p = 0.000), respiratory sinus arrhythmia (RSA) (p = 0.037), standard deviation of all NN intervals (SDNN) (p = 0.013), NN50 count divided by the total number of all NN intervals (pNN50) (p = 0.004), and square root of the mean of the sum of the squares of differences between adjacent NN intervals (RMSSD) (p = 0.002) increased, and mean heart rate decreased (p = 0.000) following long SKY. In frequency domain analysis, power of low-frequency (LF) component (p = 0.010) and LF/HF ratio (p = 0.008) decreased significantly, whereas power of high frequency (HF) significantly increased (p = 0.010). SCL decreased following long SKY, although it did not attain statistical significance. The results suggest that long SKY induces significant oscillations in cardiac autonomic tone. Parasympathetic activity increases and sympathetic activity decreases and sympathovagal balance improves following long SKY. Decrease in sympathetic activity is also demonstrated by decrease in conductance although it did not reach statistical significance. From this study it can be concluded that long SKY has a beneficial effect on cardiac autonomic tone, and psychophysiological relaxation. It may serve as a tool to improve HRV, which is the marker of cardiovascular health.


Synthesis of Cyano-Containing Phenanthridine Derivatives via Catalyst-, Base-, and Oxidant-Free Direct Cyanoalkylarylation of Isocyanides.
An efficient catalyst-, base-, and oxidant-free direct cyanoalkylarylation of isocyanides with AIBN has been developed under mild conditions. This strategy provides an elusive and rapid access to a wide range of cyano-containing phenanthridine derivatives in good yields via a one-pot alkylation/cyclization radical-cascade process. The mild reaction conditions together with no need of any catalyst, base, or oxidant make this protocol environmentally benign and practical.


Analysis of relationship between superior hypophyseal artery visualization and preservation and postoperative visual field deficit in paraclinoid aneurysm.
Direct surgery for paraclinoid aneurysms can result in visual field deficit owing to compromised blood flow to the superior hypophyseal artery (SHA). However, it is rarely visualized in angiography, and discussions regarding its preservation in the field of neuro-endovascular treatment are limited. Biplane angiographic suite with high spatial resolution has been used at our institution since 2014. Since then, there were a few cases where SHAs could be visualized via digital subtraction angiography. We retrospectively analyzed the relationship between the presences and abscence of SHAs in paraclinoid aneurysms and post-procedural visual field deficit. Sixty-three paraclinoid aneuryms treated by neuro-endovascular procedure in 2014-2018 at our neurosurgery department were analyzed. Pre- and post-procedural multiplanar reconstruction imagings of three-dimensional rotation angiography were analyzed to retrospectively investigate the SHAs. SHAs were visualized in 26 patients (41%) and the median number of pre-procedurally visualized SHAs was 0 (interquartile range 0-1). Their origins were the aneurysmal necks in 11 patients (42%). In two of the 11 cases, they were noticed before coil embolization and were able to be preserved after the procedure. In the remaining nine cases, they were not pre-procedurally detected, and coiling was normally conducted. Visual field deficit occurred in one of these nine cases, but symptoms were transient, and the patient fully recovered. Because SHAs could be visualized in >40% cases and no visual field defects occurred in cases that SHAs could be identified and preserved preoperatively, we recommend their preservation during coil embolization for paraclinoid aneurysms.


Local current density measurement using a Rogowski probe in Tokyo Spherical Tokamak-2.
A Rogowski probe consisting of a small multi-layer Rogowski coil, five magnetic pick-up coils, and a Langmuir probe was developed to measure the local current density and its direction. It can be moved along the major radius and can be turned around its axis. This probe was used to measure the current density profile near the last closed flux surface of Ohmic plasmas in Tokyo Spherical Tokamak-2. The current density profile was measured successfully with a signal to noise ratio of greater than 20.


MRI findings of hepatobiliairy fascioliasis.
Hepatobiliary fascioliasis is an uncommon disease. Depending on the stage of the disease it can present with a wide variability of clinical symptoms. Knowledge of the specific radiological findings of the disease is crucial to shorten the time to final diagnosis, which is usually long. We report a case of hepatobiliary fascioliasis in a 26-year-old woman with intermittent abdominal discomfort showing non specific findings at computed tomography and ultrasound. A hypothesis of an infectious disorder was formulated based on MRI findings and a recent history of travelling. Final diagnosis was confirmed by subsequent serology testing.


Amino acid based de Bruijn graph algorithm for identifying complete coding genes from metagenomic and metatranscriptomic short reads.
Metagenomic studies, greatly promoted by the fast development of next-generation sequencing (NGS) technologies, uncover complex structures of microbial communities and their interactions with environment. As the majority of microbes lack information of genome sequences, it is essential to assemble prokaryotic genomes ab initio aiming to retrieve complete coding genes from various metabolic pathways. The complex nature of microbial composition and the burden of handling a vast amount of metagenomic data, bring great challenges to the development of effective and efficient bioinformatic tools. Here we present a protein assembler (MetaPA), based on de Bruijn graph searching on oligopeptide spaces and can be applied on both metagenomic and metatranscriptomic sequencing data. When public homologous protein sequences are involved to guide the assembling procedures, MetaPA assembles 85% of total proteins in complete sequences with high precision of 83% on real high-throughput sequencing datasets. Application of MetaPA on metatranscriptomic data successfully identifies the majority of actively transcribed genes validated in related studies. The results suggest that MetaPA has a good potential in both metagenomic and metatranscriptomic studies to characterize the composition and abundance of microbiota.


Prognostic factors for survival in breast cancer patients who developed distant metastasis subsequent to definitive surgery.
The present study was undertaken to define the prognostic factors for overall survival subsequent to definitive surgery, and for survival after the development of distant metastasis in breast cancer patients who developed distant metastasis subsequent to definitive surgery. The records of 470 breast cancer patients with T1-3 tumours and distant metastasis following surgery were reviewed. Prognostic factors were compared to the first metastatic sites as solitary skeletal, multiple skeletal, and visceral metastases, and were analysed for overall survival following surgery and survival after metastasis. Survival curves were generated by the Kaplan-Meier method, and multivariate analysis was performed by the Cox proportional hazard model. 79 patients (17 percent) had a solitary skeletal metastasis, 105 (22 percent) had multiple skeletal metastases, and 286 (61 percent) had a visceral metastasis. The five-year overall survival was significantly better for patients with a solitary bone metastasis (73 percent) compared to patients who had multiple bone metastases (46 percent), or a visceral metastasis (22 percent) (p-value is less than 0.0001). Pathological lymph node status 3, stage IIIC, grade 3, oestrogen receptor negativity, and visceral metastases were found to have independent detrimental influence on overall survival following surgery and survival after metastasis. A long-term metastasis-free interval affected post-metastatic outcome favourably. Radiotherapy improved overall survival. Pathological lymph node status, stage, grade, and oestrogen receptor status predicted survival after surgery as well as after the development of metastasis. Solitary bone metastasis has a more favourable prognosis than multiple bone metastases, and compared to visceral metastasis, skeletal metastasis has a more favourable prognosis.


Miniaturized sample preparation method for determination of amphetamines in urine.
A simple and miniaturized sample preparation method for determination of amphetamines in urine was developed using on-column derivatization and gas chromatography-mass spectrometry (GC-MS). Urine was directly applied to the extraction column that was pre-packed with Extrelut and sodium carbonate. Amphetamine (AP) and methamphetamine (MA) in urine were adsorbed on the surface of Extrelut. AP and MA were then converted to a free base and derivatized to N-propoxycarbonyl derivatives using propylchloroformate on the column. Pentadeuterated MA was used as an internal standard. The recoveries of AP and MA from urine were 100 and 102%, respectively. The calibration curves showed linearity in the range of 0.50-50 microg/mL for AP and MA in urine. When urine samples containing two different concentrations (0.50 and 5.0 microg/mL) of AP and MA were determined, the intra-day and inter-day coefficients of variation were 1.4-7.7%. This method was applied to 14 medico-legal cases of MA intoxication. The results were compared and a good agreement was obtained with a HPLC method.


Myeloid-derived suppressor cells accumulate among myeloid cells contributing to tumor growth in matrix metalloproteinase 12 knockout mice.
Myeloid-derived suppressor cells (MDSCs) are found frequently in patients and mice bearing tumors, which derived from immature myeloid cells. In healthy individuals, immature myeloid cells formed in the bone marrow differentiating to dendritic cells, macrophages and neutrophils. However, it is unclear whether some gene deficiency will lead to MDSCs accumulation in mice without bearing tumor. Here, we observed that MDSCs accumulated in the bone marrow of matrix metalloproteinase 12 knockout mice (MMP12-/- mice) compared with wild type mice (MMP12+/+ mice). And the number of CD4+ cells dramatically decreased, regulatory T cells was up-regulation and MDSCs function were determined. The results suggested that immune surveillance have been impaired in MMP12-/- transgenic mice. After intravenous administration of B16 murine melanoma cells, MMP12-/- mice developed more metastatic pulmonary nodules than MMP12+/+ mice. Meanwhile, more MDSCs appeared in the tumors of MMP12-/- mice compared with those of MMP12+/+ mice. Mechanistically, we performed a MDSC blocking assay, finding that blockade of MDSCs resulted in reducing growth of tumors in MMP12-/- mice. Furthermore, we ascertained that macrophages in MMP12-/- mice abundantly secrete IL-1β in bone marrow which induce the accumulation of MDSCs in the bone marrow. Together, these results demonstrated that the macrophages in MMP12-/- mice could crosstalk with myeloid cells through IL-1β, inducing MDSCs accumulation, then contributing to tumor growth. It has revealed that the critical roles of macrophage in myeloid cells differentiation.


Comparative radiologic evaluation of percutaneous endoscopic lumbar discectomy and open microdiscectomy: a matched cohort analysis.
Only a few studies comparing percutaneous endoscopic discectomy and open discectomy have been reported in the literature. The purpose of this study was to compare the radiographic changes in patients treated with percutaneous endoscopic lumbar discectomy (PELD) with those of patients treated with open lumbar microdiscectomy (OLM). A total of 30 patients who underwent PELD with a minimum three years of follow-up were randomly selected. To compare with the PELD group, 30 patients who underwent OLM during the same period were also randomly selected according to sex, age, and disc level. The clinical outcomes were evaluated by the Macnab criteria. Statistical analysis was performed using independent sample t-test, paired sample t-test, chi-square test, Fisher's exact test, and analysis of variance (ANOVA). The successful clinical outcomes were 96.7% in the PELD group and 93.3% in the OLM group. Among the various radiological parameters, changes of disc height (1.41 +/- 1.19 mm in the PELD group and 2.29 +/- 2.12 mm in the OLM group, p=0.024) and foraminal height (1.26 +/- 0.91 mm in the PELD group and 1.85 +/- 0.92 mm in the OLM group, p=0.017) were significantly different between the two groups. Although the clinical outcomes were similarly satisfactory in both groups, PELD is a less invasive procedure than open microdiscectomy in s elected cases.


Fatality following right atrial perforation by a screw-in pacemaker electrode.
This paper describes the first reported fatality from right atrial perforation complicating the insertion of a screw-in right atrial pacemaker electrode. The patient was an 84-year-old woman with the sick sinus syndrome who also had hepatic cirrhosis.


Simple method for large-scale isolation and purification of gangliosides by non-ionic adsorption chromatography.
A type of non-ionic adsorption resin, X-5, was used in the isolation and purification of brain gangliosides. Hydrolysis with base treatment was carried out for the purpose of eliminating contaminants. The major advantages of the new procedure, compared to conventional methods, were the shorter separation time, higher loading capacity (80 micromol LBSA per gram resin), and recovery (98%) of separated ganglioside fractions with little solvent. It is a practical way for large-scale isolation and purification of gangliosides.


Lumbar thermography in discogenic disease.
Thermography is a simple, noninvasive outpatient procedure which can be performed on patients with clinical symptoms of a herniated disk. A positive thermogram usually indicates that an abnormality will be found by myelography. However, the myelographic findings cannot be predicted by a negative lumbar thermogram.


Disseminated aspergillosis in a renal transplant patient: Diagnostic difficulties re-emphasized.
An asymptomatic and radiographically occult lung abscess was the primary focus of infection in this case of fatal disseminated aspergillosis in a renal transplant recipient. Extensive neurological evaluation in response to a change in personality failed to reveal a brain abscess, which was the cause of death. This case illustrates the variability in presentations of aspergillosis and the continuing difficulties in diagnosing this infection in immunosuppressed patients.


Integration of safety pharmacology endpoints into toxicology studies.
In the ILSI Human Toxicity Program, human toxicity was identified with 94% in studies of 1 month or less duration. Safety pharmacology studies and 1 month toxicity studies are prerequisites of INDs. These studies contributed in 69% to the predictivity of human toxicity. Correlating data from pharmacology and toxicology data will therefore enhance the predictivity of human toxicity. The ILSI Human Toxicity Program also showed that non-rodent toxicology studies were more predictive of human toxicity than rodents. Consequently, the usage of non-rodents, especially dogs, produces data more relevant to the safety of humans. Integration of data from safety pharmacology and pharmacological endpoints from integrated toxicology studies, which cover a wide dose range, allow data interpretation also concerning chronic effects. Differences in relation to chronic exposure and species specific pharmacodynamic effects can be taken into consideration. In vivo data in pharmacology are taken from a larger number of species. Usually, pharmacokinetic data and histopathology are often lacking in pharmacology (e.g. guinea pig). Studies in a smaller number of species, which are incorporating pharmacology, pharmacodynamic and toxicology, allow also crossinterpretation with data from clinical chemistry, haematology and histopathology. Endpoints relating to behaviour (functional observation battery/FOB) and cardiovascular toxicity can be integrated into regulatory toxicology. Technical progress in non-invasive methodology and refined measurements for pharmacological parameters and standardization of study design allow the incorporation into regulatory toxicity studies today. The limitations of conducting pharmacological measurements in regulatory toxicology studies are acknowledged. Safety pharmacology studies should complement toxicity studies in terms of choice of species and dose regimen. Ethical usage of animals, especially dogs or monkeys, can only be justified in the future, when more clinically relevant data can be gained from fewer in vivo studies. Multidisciplinary co-operation between pharmacology, pharmacokinetics and toxicology will lead to refinements and reduction of in-vivo studies when functional parameters are integrated into regulatory studies.


Alteration of thyroid hormone economy during alcohol withdrawal in alcoholics.
Alcohol and alcohol withdrawal may affect nutritional status in many different ways, including effects on thyroid activity. The influence of alcohol withdrawal on thyroid hormone economy was investigated by measurements of changes in the serum concentrations of thyroxine (T4), 3, 5, 3'-triiodothyronine (T3), 3, 5, 5'-triiodothyronine (reverse T3, rT3), and thyrotropin (TSH) in chronic alcoholics experiencing different degrees of alcohol abstinence. In addition, the serum concentrations of ethanol were measured at entrance. There was no significant correlation between the entrance serum ethanol levels, on the one hand, and those of T4, T3, rT3, or TSH, on the other. However, during severe ethanol abstinence (with or without delirium tremens), there was a significant increase in the serum levels of T4 and rT3, but not in those of T3 and TSH. These findings indicate that (severe) alcohol abstinence can interfere with thyroid hormone economy, either by enhancing thyroid hormone secretion or by reducing T4 and rT3 deiodination. It is an open question whether this represents a beneficial adaptation to the metabolic disturbance caused by alcohol intoxication and abstinence, or an additional derangement that warrants nutritional or other therapeutic measures.


CDK2 knockdown enhances head and neck cancer cell radiosensitivity.
Cyclin-dependent kinase 2 (CDK2) is critically involved in cell cycling and has been proposed as a potential cancer target. It remains largely elusive whether CDK2 targeting alters the tumor cell radiosensitivity. CDK2(-/-) and wild type (WT) mouse embryonic fibroblasts (MEF) as well as six human head and neck squamous cell carcinoma (HNSCC) cell lines (SAS, FaDu, Cal-33, HSC-4, UTSCC-5, UTSCC-8) were used. Upon CDK2 knockdown using small interfering technology, colony formation, DNA double-strand breaks (DSB), cell cycle distribution and expression and phosphorylation of major proteins regulating cell cycle and DNA damage repair were examined. CDK2(-/-) MEF and CDK2 HNSCC knockdown cell cultures were more radiosensitive than the corresponding controls. Repair of DSB was attenuated under CDK2 knockout or knockdown. In contrast to data in MEF, combined CDK2 knockdown with irradiation showed no cell cycling alterations in SAS and FaDu cultures. Importantly, CDK2 knockdown failed to radiosensitize SAS and FaDu when cultured in a more physiological three-dimensional (3D) extracellular matrix environment. Our findings suggest that targeting of CDK2 radiosensitizes HNSCC cells growing as monolayer. Additional studies performed under more physiological conditions are warranted to clarify the potential of CDK2 as target in radiotherapy.


Preliminary crystallographic analysis of two hypothetical ribose-5-phosphate isomerases from Streptococcus mutans.
Study of the enzymes from sugar metabolic pathways may provide a better understanding of the pathogenesis of the human oral pathogen Streptococcus mutans. Bioinformatics, biochemical and crystallization methods were used to characterize and understand the function of two putative ribose-5-phosphate isomerases: SMU1234 and SMU2142. The proteins were cloned and constructed with N-terminal His tags. Protein purification was performed by Ni(2+)-chelating and size-exclusion chromatography. The crystals of SUM1234 diffracted to 1.9 Å resolution and belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 48.97, b = 98.27, c = 101.09 Å, α = β = γ = 90°. The optimized SMU2142 crystals diffracted to 2.7 Å resolution and belonged to space group P1, with unit-cell parameters a = 53.7, b = 54.1, c = 86.5 Å, α = 74.2, β = 73.5, γ = 83.7°. Initial phasing of both proteins was attempted by molecular replacement; the structure of SMU1234 could easily be solved, but no useful results were obtained for SMU2142. Therefore, SeMet-labelled SMU2142 will be prepared for phasing.


Radiological features of progressive tumoral calcinosis in chronic renal failure.
We present the case of a young adult patient with chronic renal failure who developed painful subcutaneous nodules after failed renal transplant and recommencing dialysis. These nodules were juxta-articular in location and initially located over both shoulders. Radiological evaluation suggested tumoral calcinosis. The patient was placed on a strict dialysis and dietary regimen but was suboptimally compliant with same. The patient developed progressive disease with an increase in size and number of juxta-articular calcified soft-tissue masses. However, 6 months following a second renal transplant clinical and radiological follow up demonstrated marked resolution both in symptomatology and radiographic findings. We present the plain radiographic, CT and MRI findings which demonstrate the typical radiological features of tumoral calcinosis. We correlate these findings with clinical course and histological findings following surgical excision of one of these masses.


New techniques and developments of stenting for infrainguinal arterial occlusive disease: are the results any better than balloon angioplasty alone?
Infrainguinal occlusive disease is a complex problem necessitating the cooperation of both medical and surgical therapies to aid limb salvage and alleviate symptoms. Endovascular therapies are varied, with no treatment clearly outweighing the other in terms of efficacy and durability. Angioplasty for focal stenosis has gained ground as the treatment of choice when indicated. There has also been a rapid evolution in stent technology, from early stainless steel wall stents to today's drug eluting nitinol stents. In this article, we examine the literature on these new technologies and treatment options and make recommendations based on the best data available.


The role of the IL-23/IL-17 axis in the pathogenesis of Graves' disease.
This study is to explore the role of IL-23/IL-17 axis in subjects with Graves' disease, while IL-23/IL-17 axis plays an important role in a number of autoimmune diseases, but it's not clear in Graves' disease. Thirty-three patients with Graves' disease as a GD group, 15 patients with euthyroid GD as eGD group and 22 healthy volunteers as a control group whose age- and sex-matched. Peripheral blood was collected and peripheral blood mononuclear cells (PBMCs) were isolated in the both groups, then PBMCs were cultured in the presence or absence of IL-23 in vitro. The expression of retinoid-related orphan receptor gamma t (RORγt) and IL-17 mRNA were examined by Semi-quantitative RT-PCR, and the levels of IL-17 protein were measured by enzyme-linked immunosorbent assay. The expression of RORγt, IL-17 mRNA and IL-17 protein levels were markedly higher in GD and euthyroid GD group as compared with the control group. IL-17 levels were still higher in euthyroid GD patients. When PBMCs derived from the three groups were cultured in vitro with or without IL-23, the expression of RORγt in GD group with IL-23 dramatically increased as compared with that in GD group without IL-23 and in control group with IL-23. RORγt expression of PBMCs from eGD group cultured with IL-23 was increased compared with that cultured without IL-23. The levels of IL-17 mRNA and the protein were also significantly higher than that of GD and eGD cultured without IL-23 and control group. There was no difference of the expression of RORγt mRNA and IL-17 protein levels between GD and eGD group cultured with or without IL-23. Our studies demonstrated that IL-23/IL-17 axis is associated with the pathogenesis of Graves' disease in it activated term. This effect is not dependent on thyroid function, but may be associated to the immunity.


Replication proteins and human disease.
In this article, we discuss the significance of DNA replication proteins in human disease. There is a broad range of mutations in genes encoding replication proteins, which result in several distinct clinical disorders that share common themes. One group of replication proteins, the MCMs, has emerged as effective biomarkers for early detection of a range of common cancers. They offer practical and theoretical advantages over other replication proteins and have been developed for widespread clinical use.


Molecular Crowding Effects on Microgel-Tethered Oligonucleotide Probes.
Microgel tethering is a nontraditional method with which to bind oligonucleotide hybridization probes to a solid surface. Microgel-tethering physically positions the probes away from the underlying hard substrate and maintains them in a highly waterlike environment. This paper addresses the question of whether molecular crowding affects the performance of microgel-tethered molecular beacon probes. The density of probe-tethering sites is controlled experimentally using thin-film blends of biotin-terminated [PEG-B] and hydroxyl-terminated [PEG-OH] poly(ethylene glycol) from which microgels are synthesized and patterned by electron beam lithography. Fluorescence measurements indicate that the number of streptavidins, linear DNA probes, hairpin probes, and molecular beacon probes bound to the microgels increases linearly with increasing PEG-B/PEG-OH ratio. For a given tethering-site concentration, more linear probes can bind than structured probes. Crowding effects emerge during the hybridization of microgel-tethered molecular beacons but not during the hybridization of linear probes, as the tethering density increases. Crowding during hybridization is associated with conformational constraints imposed by the close proximity of closed and hybridized structured probes. The signal-to-background ratio (SBR) of hybridized beacons is highest and roughly constant for low tethering densities and decreases at the highest tethering densities. Despite differences between microgel tethering and traditional oligonucleotide surface-immobilization approaches, these results show that crowding defines an optimum tethering density for molecular beacon probes that is less than the maximum possible, which is consistent with previous studies involving various linear and structured oligonucleotide probes.


Quantitative iTRAQ-based proteomic analysis of differentially expressed proteins in aging in human and monkey.
The underlying physiological mechanisms associated with aging are still complex and unclear. As a very important tissue of human body, the circulatory system also plays a very important role in the process of aging. In this study, we use the isobaric tags for relative and absolute quantification (iTRAQ) method to identify differentially expressed proteins in plasma for humans and monkeys between young and aged. Western blotting and behavioral experiment in mice were performed to validate the expression of the candidate protein. Between the young / the old humans and the young / the old monkeys 74 and 69 proteins were found to be differently expressed, respectively. For the human samples, these included 38 up-regulated proteins and 36 down-regulated proteins (a fold change ≥1.3 or ≤ 0.667, p value ≤0.05).For the monkey samples, 51 up-regulated proteins and 18 down-regulated proteins (a fold change ≥1.3 or ≤ 0.667, p value ≤0.05). KEGG pathway analysis revealed that phagosome, focal adhesion, ECM-receptor interaction and PI3K/AKT signaling pathway were the most common pathways involved in aging. We found only IGFBP4 protein that existed in up-regulated proteins in aged both for human and monkey. In addition, the differential expression of IGFBP4 was validated by western blot analysis and IGFBP4 treatment mimicked aging-related cognitive dysfunction in mice. This first, the integrated proteomics for the plasma protein of human and monkey reveal one protein-IGFBP4, which was validated by western blotting and behavioral analysis can promote the process of aging. And, iTRAQ analysis showed that proteolytic systems, and inflammatory responses plays an important role in the process of aging. These findings provide a basis for better understanding of the underlying mechanisms involved in aging.


Multisensory processing and oscillatory gamma responses: effects of spatial selective attention.
Here we describe an EEG study investigating the interactions between multisensory (audio-visual) integration and spatial attention, using oscillatory gamma-band responses (GBRs). The results include a comparison with previously reported event-related potential (ERP) findings from the same paradigm. Unisensory-auditory (A), unisensory-visual (V), and multisensory (AV) stimuli were presented to the left and right hemispaces while subjects attended to a designated side to detect deviant target stimuli in either sensory modality. For attended multisensory stimuli we observed larger evoked GBRs approximately 40-50 ms post-stimulus over medial-frontal brain areas compared with those same multisensory stimuli when unattended. Further analysis indicated that the integration effect and its attentional enhancement may be caused in part by a stimulus-triggered phase resetting of ongoing gamma-band responses. Interestingly, no such early interaction effects (<90 ms) could be found in the ERP waveforms, suggesting that oscillatory GBRs may be more sensitive than ERPs to these early latency attention effects. Moreover, no GBR attention effects could be found for the unisensory auditory or unisensory visual stimuli, suggesting that attention particularly affects the integrative processing of audiovisual stimuli at these early latencies.


Recent advances in the management of metastatic prostate cancer: optimizing use of existing therapies, while searching for novel interventions.
Summarizes recent advances in the treatment of metastatic castration-sensitive and castration-resistant prostate cancer. New randomized data suggest a survival advantage to early abiraterone in castration-sensitive metastatic prostate cancer. Prospective and retrospective studies are examining sequencing of existing cytotoxic and androgen-receptor-targeted therapies in both castration-sensitive and castration-resistant disease. Genomic analysis of both circulating tumor cells and circulating tumor nucleic acids is being examined as a potential method for selecting existing therapies and identifying novel therapeutic targets. Finally, immunotherapy combinations are being evaluated in the setting of advanced prostate cancer. In this review, we hope to summarize the recent data supporting the use of early abiraterone in castration-sensitive metastatic prostate cancer and discuss how this data might be incorporated with previous trials showing a survival advantage to early docetaxel. We present recent series examining sequencing of approved therapies as well as trials evaluating novel biomarkers and genomic analyses designed to help choose from among approved therapies or evaluate drugs in development. Lastly, we review ongoing trials examining novel immunotherapy combinations in advanced prostate cancer.


Removal of Calcareous Concretions from Marine Archaeological Ceramics by Means of a Stimuli-Responsive Hydrogel.
The presence of calcareous concretions on the surface of marine archaeological ceramics is a frequently observed phenomenon. It is necessary to remove these materials when the deposits obscure the feature of ceramics. Unfortunately, calcareous concretions provide distinctive documentation of the burning history of ceramics. The interaction of acid solution or detachment of the deposit layers in physical ways leads to the loss of archeological information. To prevent the loss of archeological information and to achieve precise and gentle concretion removal, responsive hydrogel cleaning systems have been developed. The hydrogels synthesized are composed of networks of poly(vinyl acetate)/sodium alginate that exhibit desirable water retention properties, are responsive to Ca2+ ions, and do not leave any residues after undergoing cleaning treatment. Four distinct compositions were selected. The study of water retention properties involved quantifying the weight changes. The composition was obtained from Fourier transform infrared spectra. The microstructure was obtained from scanning electron microscopy. The mechanical properties were obtained from rheological measurements. To demonstrate both the efficiency and working mechanism of the selected hydrogels, a representative study of mocked samples is presented first. After selecting the most appropriate hydrogel composite, a cleaning process was implemented on the marine archaeological ceramics. This article demonstrates the advantages of stimuli-responsive hydrogels in controlling the release of acid solution release, thereby surpassing the limitations of traditional cleaning methods.


Theoretical assessment of the oligolysine model for ionic interactions in protein-DNA complexes.
The observed salt dependence of charged ligand binding to polyelectrolytes, such as proteins to DNA or antithrombin to heparin, is often interpreted by means of the "oligolysine model." We review this model as derived entirely within the framework of the counterion condensation theory of polyelectrolytes with no introduction of outside assumptions. We update its comparison with experimental data on the structurally simple systems for which it was originally intended. We then compute the salt dependence of the binding free energy for a variety of protein-DNA complexes with nonlinear Poisson-Boltzmann (NLPB) simulation methods. The results of the NLPB calculations confirm the central prediction of the oligolysine model that the net charge density of DNA remains invariant to protein binding. Specifically, when a cationic protein residue penetrates the layer of counterions condensed on DNA, a counterion is released to bulk solution, and when an anionic protein residue penetrates the condensed counterion layer, an additional counterion is condensed from bulk solution. We also conclude, however, that the cumulative effect of charged protein residues distant from the binding interface makes a significant contribution to the salt dependence of binding, an observation not accommodated by the oligolysine model.


A biomaterials approach to Schwann cell development in neural tissue engineering.
Schwann cells, in addition to forming myelin sheaths, have pivotal roles in regeneration of injured axons in the peripheral nervous system such as producing a natural permissive conduit between distal and proximal stumps and secreting nerve growth factors. Due to the atrophy and senescence of Schwann cells in long nerve gap, and the need to ensure the presence of nerve growth factors and basal lamina tubes for axon regeneration in a critical time, injection of Schwann cells with the aid of an engineered conduit seems to be an effective approach to induce axon regrowth. Stem cells with high differentiation and proliferation capability can provide an adequate number of Schwann cells in healthy state for regeneration purposes. Guidance of stem cells differentiation into desired lineages, control of implanted Schwann cells fate, maintenance of nerve growth factors expression, and guidance of axon regrowth are possible with the aid of biomaterials with appropriate chemical, physical, and mechanical properties. Biomaterials' surface chemistry and biomolecules interacting with cells' receptors initiate specific intracellular signaling cascades and direct cells fate. In addition, biomaterials' surface topography in association with cells contact area, focal adhesion, and cytoskeletal remodeling by mechanotransduction process influences cells behavior and induces specific differentiation. The main objective of this review is to investigate the chemical, topographical, and mechanical properties of biomaterials which influence the fate of Schwann cells and the nerve regeneration process.


[Current Status and Problems of Living-donor Lobar Lung Transplantation].
Living-donor lobar lung transplantation (LDLLT) has become an important life-saving option for patients with severe respiratory disorders in order to address the current severe shortage of brain-dead donor organs. Although LDLLT candidates were basically limited to critically ill patients who would require hospitalization, the long-term use of steroids, and/or mechanical respiratory support before transplantation, LDLLT provided good post-transplant outcomes, comparable to brain-dead donor lung transplantation( BDLT). In Kyoto University, the 1-, 5- and 10-year survival rates were 91%, 79% and 62% after LDLLT and 92%, 72% and 65% after BDLT, respectively. Various transplant procedures have recently been developed in LDLLT in order to deal with the issue of graft size mismatching. Native upper lobe-sparing and/or right-to-left inverted transplantation have been performed for undersized grafts, while single-lobe transplantation has been employed for oversized grafts. These new transplant procedures have provided favorable post-transplant outcomes.


Malignant ascites of serous papillary ovarian adenocarcinoma. An immunocytochemical study of the tumor cells.
In 17 malignant peritoneal effusions due to papillary serous adenocarcinoma of the ovary, the reaction patterns of the tumor cells to monoclonal antibodies (MAbs) against surface antigens were studied and compared with the reaction patterns of mesothelial cells in the same effusions. The following surface markers were used with the adhesive slide method: epithelial membrane antigen (EMA), human epithelium-specific cell surface antigen (HEA-125), human endothelial antigen (BMA-120), carcinoembryonic antigen (CEA 3-13), an antibody against natural killer cells and cytotoxic cells (BMA-070), granulocyte antigen (Leu M1) and leukocyte antigen of class I (HLA-1). In all cases, from 30% to 95% of the tumor cells reacted with EMA and HEA-125. Tumor cells showed a positive staining with CEA 3-13 in only five cases. In all cases, from 75% to 95% of the tumor cells reacted positively with BMA-120. The reactivity of a few mesothelial cells with EMA and of all mesothelial cells with BMA-120 did not interfere with the identification of positive tumor cells since the reaction patterns were different. Interestingly, our study demonstrated that BMA-070, an MAb identifying natural killer cells and cytotoxic cells, is also a most useful tumor marker. The same was found to be true for Leu M1, an MAb originally thought to react only with granulocytes. The tumor cells showed a partial or total loss of the expression of HLA-1 reactivity. Since all cases were immunocytochemically positive for tumor cells while conventional cytology was positive in only 13 of the cases, the immunocytochemical analysis of malignant peritoneal effusions due to papillary serous adenocarcinoma of the ovary seems able to improve the cytologic diagnosis of the fluids.


The promoter for a variant surface glycoprotein gene expression site in Trypanosoma brucei.
The variant-specific surface glycoprotein (VSG) gene 221 of Trypanosoma brucei is transcribed as part of a 60 kb expression site (ES). We have identified the promoter controlling this multigene transcription unit by the use of 221 chromosome-enriched DNA libraries and VSG gene 221 expression site specific transcripts. The start of transcription was determined by hybridization and RNase protection analysis of nascent RNA. The 5' ends of the major transcripts coming from the initiation region map at nucleotide sequences that do not strongly resemble rRNA transcriptional starts even though the transcripts are synthesized by an RNA polymerase highly resistant to alpha-amanitin. The cloned VSG gene 221 ES transcription initiation region promotes high CAT gene expression, when reintroduced by electroporation into T. brucei. We show that the activity of this expression site is controlled at or near transcription initiation in bloodstream trypanosomes. The 221 ES is inactivated without any sequence alteration within 1.4 kb of the transcription start site. This excludes mechanisms of promoter inactivation involving DNA rearrangements in the vicinity of the transcription start site, e.g. promoter inversion or conversion.


The Ups and Downs of Parenting Young Children With Type 1 Diabetes: A Crowdsourcing Study.
Parenting young children with type 1 diabetes (YC-T1D) entails pervasive challenges; parental coping may influence child and parent outcomes. This study used a qualitative descriptive design to describe these challenges comprehensively to inform the user-centered design of an Internet coping resource for parents. A "Parent Crowd" of 153 parents of children with T1D onset at ≤ 5 years old submitted textual responses online to open-ended questions about parenting YC-T1D. Systematic coding organized responses into domains, themes, and examples. A supplemental focus group of racial/ethnic minority parents enhanced the sample's diversity and validated findings from the Parent Crowd. Similar domains and themes emerged from responses of crowdsourcing and focus group participants. In each domain, parenting YC-T1D was challenging, but there was also substantial evidence of positive coping strategies and adaptability. The study yielded rich data to inform user-centered design of an Internet resource for parents of YC-T1D.


The effects of ethanol on spatial and nonspatial memory in adolescent and adult rats studied using an appetitive paradigm.
Adolescent rats have been reported to be less sensitive than adults to many acute ethanol effects, including ethanol-induced sedation and motor impairment, but conversely more sensitive to ethanol-induced disruptions in spatial memory in a Morris water maze (Markwiese et al., 1998). The present study examined adolescent and adult rats trained for 6 days under spatial or nonspatial versions of a presumably less stressful sand box maze. Moderately food-deprived animals were given 0, 0.5, or 1.5 g/kg ethanol intraperitoneally 30 min before training each day, but were tested without ethanol or reinforcer on test day. Spatial acquisition was impaired by 1.5 g/kg in adults but not adolescents, with no ethanol impairment on the nonspatial task at either age. These results are opposite the ontogenetic profile reported by Markwiese et al., (1998) and may reflect differential activation of prefrontal cortex or other stress-sensitive forebrain regions by the two tasks across age.


A simplified method for determining the average life expectancy in the Republic of Bulgaria.
A simplified method was used in the present study to calculate the average life expectancy of newborn children in Bulgaria. In contrast to the classical methods for constructing mortality tables, this method is not time consuming and does not require complex mathematical calculations and therefore easily accessible for public health bodies and institutions. The average life expectancy of newborn children, by sex and place of residence, was calculated for the following periods: 1994- 1946, 1954-1956, 1963-1965, 1973-1975, 1983-1985. Relevant conclusions and recommendations were made.


Multiple-scattering effects on infrared scattering measurements used to characterize droplet size and volume fraction distributions in diesel sprays.
We quantify the maximum error due to multiple-scattering effects for an infrared scattering droplet izing technique. Errors in Sauter mean diameters (SMDs) and liquid volume fractions were estimated lased on experimentally determined polarization properties of the scattered light. Light that is multiply scattered from spherical particles becomes randomly polarized, whereas singly scattered light from a spherical particle contains no cross-polarization scattering component. Therefore measurement of the cross-polarization component (in this case parallel) of the scattering signal is a measure of the multiply scattered light. A ratio of parallel to perpendicular polarized scattered light was experimentally determined and used to calculate an error due to multiple scattering. The infrared scattering measurements and polarization measurements used to quantify the multiple-scattering errors were applied to a typical diesel spray that was injected into three different background conditions: a room ambient condition; a room-temperature, high-pressure condition; and a combusting condition. Droplet SMD, liquid volume fraction, and multiple-scattering errors were determined for a number of locations within the spray; results indicate that the combusting case is negligibly affected by multiple scattering. However, the room ambient case exhibited notable errors due to multiple scattering near the centerline of the spray, and the high-pressure case demonstrated susceptibility to multiple scattering throughout all regions investigated. It is important to note, however, that multiple-scattering errors in many cases translate into relatively small effects on the reported droplet sizes.


Synthesis of Copper Telluride Thin Films by Electrodeposition and Their Electrical and Thermoelectric Properties.
Intermetallic copper telluride thin films, which are important in a number of electronics fields, were electrodeposited using a potentiostatic method in low-pH aqueous electrolyte baths with various ion-source concentrations, and the electrical properties of the formed films were investigated after exfoliation from the substrate. The films were electrochemically analyzed by cyclic voltammetry, while surface and cross-sectional morphologies, compositional ratios, and electrical properties were analyzed by scanning electron microscopy, X-ray diffractometry, X-ray photoelectron spectroscopy, ultraviolet photoelectron spectroscopy, and Hall-effect experiments. The copper telluride thin films, which were synthesized at various potentials in each bath, exhibit different composition ratios and structures; consequently, they show a variety of electrical and thermoelectric properties, including different electrical conductivities, carrier concentrations, mobilities, and Seebeck coefficients. Among them, the thin film with a 1:1 Cu:Te ratio delivered the highest power factor due to carrier filtering at the interface between the two phases.


The 'borderline' smear in men with urethritis.
Four hundred three men with signs and symptoms of urethritis were examined by stained slide and culture of urethral exudate. Of these slides, 14.1% were interpreted as "borderline" for gonorrhea, ie, showing typical Gram-negative diplococci on microscopic examination located extracellularly only. Of these, only 10.5% were culture positive for Neisseria gonorrhoeae. Patients with urethritis whose slides are "borderline" should be treated as for nongonococcal urethritis with tetracycline hydrochloride and not with aqueous penicillin G procaine.


Screening for oral cancer: contributing to the debate.
Screening, or "case detection", is controversial and central to much debate in the world of medicine. In the present study, we evaluate oral cancer screening against the National (UK) Screening Committee criteria in the context of the most recent research in this field. Oral cancer is a complex, debilitating disease that is increasing in incidence in the UK and in most parts of Western Europe. It has multifactorial etiology, and these major risk factors are well researched, allowing definition of an "at-risk" population. However, our understanding of its natural history of progression from potentially malignant disorders to malignancy is limited; the field lacks high-quality, randomized, controlled trials, bar one published study. Evidence is also available to suggest that visual screening by sufficiently trained examiners results in earlier detection (down staging) of the disease, which lends itself towards more successful treatment. Sensitive screening tools to aid and confirm findings following a visual inspection are yet to be developed. Nevertheless, new tests continue to arise based on knowledge gleaned from research into the biomarkers. This review discusses the evidence based around the oral cancer screening debate and highlights areas in which more research is required before the advent of a successful and effective screening program.


Immunoglobulin (Gm) allotype frequencies in idiopathic membranous nephropathy and minimal change nephropathy.
40 Caucasoid patients with idiopathic membranous nephropathy (IMN) and 49 Caucasoid patients with minimal change nephropathy (MCN) were immunoglobulin allotyped for the Gm markers G1m (1, 2, 3) and G3m (5, 11, 21). Compared with normal controls the IMN group had a significantly decreased incidence of the G1m (3); G3m (5, 11) phenotype (P = less than 0.005). This decrease was accompanied by concommitant increase in both the G1m (1, 3); G3m (5, 11, 21) and the G1m (1, 2, 3); G3m (5, 11, 21) phenotypes. The result was most pronounced in IMN patients with deteriorating renal function. In contrast no significant differences were observed between the Gm phenotype frequencies of the MCN patients and controls.


AAC and Autism: Manual Signs and Pecs, a Comparison.
Autism Spectrum Disorders (ASD) represent a heterogeneous group of disorders, with onset in developmental age, which present a clinical expressiveness that varies from subject to subject and in the same subject over time. The DSM 5 defines Autism Spectrum Disorders according to two main criteria: persistent deficits in social communication and social interaction in multiple contexts and limited and repetitive patterns of behavior, interests or activities. This disorder can manifest itself across a broad spectrum of severity levels. Indeed, ASD includes clinical conditions from low functioning (LF-Low Functioning) to high functioning (HF-High Functioning), taking cognitive and adaptive functioning as a reference. One of the main characteristics of individuals with ASD is a delay in receptive and expressive communication. These deficits have led to the identification of evidence-based practices, particularly for those with severe communication difficulties. Augmentative Alternative Communication (AAC) has been implemented to compensate for deficits in functional communication and language skills in individuals with complex communication deficits. The AAC comprises communication systems including the Manual Signs, speech and image output devices (Communicators), and Image Exchange Systems (PECS); these systems have been shown to actually improve various abilities in autism such as social skills, modify and improve dysfunctional behaviors and, above all, improve learning. Recent meta-analyses have shown how PECS and Manual Sign can have great effects on the communication skills of young people with autism. The aim of this study is to compare these two types of intervention to improve communication in terms of vocalization in subjects with ASD and try to understand which of the two lead to more significant and rapid improvements.


Unique microglia expression profile in developing white matter.
Recently we demonstrated that amoeboid microglia in white matter regions are essential for proper oligodendrocyte homeostasis and myelinogenesis in the first postnatal week. Amoeboid microglia in the mouse corpus callosum change their activation profile within few days after postnatal day (P)7 with microglia of the cerebellum showing similar features. Here we expanded our previous transcriptional analysis and performed detailed bulk RNA sequencing of microglia from corpus callosum, cortex and cerebellum at P7, P10 and P42. The goal of this study was to identify a specific gene profile for both, white matter and grey matter microglia during development. Microglia in white matter regions display unique characteristics in the first postnatal week of murine life. In both the corpus callosum and cerebellum microglia show amoeboid morphology and a similar transcription profile during development including high expression of genes related to priming of microglia, phagocytosis and migration at P7; characteristics which are already lost at P10. Together these data verify our previous transcriptional data obtained by microarray analysis and enable a more complete view into white matter and grey matter microglia at different developmental stages.


Tom goodey: the father of nematology in britain.
Tom Goodey O.B.E., D.Sc., F.R.S. is generally recognized as the Father of Nematology in Britain. Although his early postgraduate work was on soil protozoa, from 1920 he worked exclusively on nematodes. His first text book, Plant Parasitic Nematodes and the Diseases They Cause, published in 1933, was a notable landmark in the development of nematology (48). His second book Soil and Freshwater Nematodes (80) indicated his breadth of understanding of this vast group of animals. From 1921 until 1946 he was a member of the team working under Professor R.T. Leiper based for most of that time at the Institute of Agricultural Parasitology, Winches Farm, St. Albans, England. He was author, or coauthor, of 125 publications, which included the proposal of 9 new genera, 37 new species and 49 detailed redescriptions of nematodes. In 1947 he was made head of the newly formed Nematology Department at Rothamsted Experimental Station, where he stayed until his retirement in 1952. In his later years he struck up a very close friendship with Gerald Thorne, the American nematologist, with whom he exchanged ideas on techniques in hematology. In 1951, he was responsible for the very successful nematology symposium held in Harpenden, which marked the beginning of the biennial nematology symposia in Europe. As well as a very full and successful scientific career, he was also a professional singer with a fine tenor voice and he frequently performed for the theater, concert hall, and radio broadcasts under his stage name of Roger Clayson.


The antiretrovirus drug 3'-azido-3'-deoxythymidine increases the retrovirus mutation rate.
It was previously observed that the nucleoside analog 5-azacytidine increased the spleen necrosis virus (SNV) mutation rate 13-fold in one cycle of retrovirus replication (V. K. Pathak and H. M. Temin, J. Virol. 66:3093-3100, 1992). Based on this observation, we hypothesized that nucleoside analogs used as antiviral drugs may also increase retrovirus mutation rates. We sought to determine if 3'-azido-3'-deoxythymidine (AZT), the primary treatment for human immunodeficiency virus type 1 (HIV-1) infection, increases the retrovirus mutation rate. Two assays were used to determine the effects of AZT on retrovirus mutation rates. The strategy of the first assay involved measuring the in vivo rate of inactivation of the lacZ gene in one replication cycle of SNV- and murine leukemia virus-based retroviral vectors. We observed 7- and 10-fold increases in the SNV mutant frequency following treatment of target cells with 0.1 and 0.5 microM AZT, respectively. The murine leukemia virus mutant frequency increased two- and threefold following treatment of target cells with 0.5 and 1.0 microM AZT, respectively. The second assay used an SNV-based shuttle vector containing the lacZ alpha gene. Proviruses were recovered as plasmids in Escherichia coli, and the rate of inactivation of lacZ alpha was measured. The results indicated that treatment of target cells increased the overall mutation rate two- to threefold. DNA sequence analysis of mutant proviruses indicated that AZT increased both the deletion and substitution rates. These results suggest that AZT treatment of HIV-1 infection may increase the degree of viral variation and alter virus evolution or pathogenesis.


Expression of cytochrome P450 2A5 in a C57BL/6J mouse model of nonalcoholic fatty liver disease.
Cytochrome P450 2A5 (CYP2A5) expression is induced during the hepatotoxicity caused by various hepatotoxins and hepatitis. However, CYP2A5 expression during nonalcoholic fatty liver disease (NAFLD) is still unknown. In this study, serum biochemical parameters and liver histopathological analyses found that NAFLD had developed in C57BL/6J mice via administration of a high-fat diet continuously for 8 weeks. Subsequently, CYP2A5 expression was probed in the mice diagnosed with NAFLD that were treated with or without pyrazole, the inducer of chemical liver injury. It is shown that hepatic CYP2A5 mRNA, protein expression and coumarin 7-hydroxylase activity are enhanced with high-fat feed, and that pyrazole is able to further increase CYP2A5 expression and activity in mice with NAFLD. These results revealed that CYP2A5 is elevated during NAFLD and suggested that pyrazole and NAFLD act synergistically to induce the expression of CYP2A5 via an unclear mechanism.


[Investigation and analysis of the self-esteem level and social adaptation ability of hospitalized burn patients].
To investigate the self-esteem level and social adaptation ability of hospitalized burn patients in our burn ward. One hundred and twenty hospitalized burn patients in our burn ward were enrolled in the study and evaluated according to their sex, severity of burn injury and education level. Their self-esteem level and social adaptation ability were scored with the Felling of Inadequacy Scale and Abbreviated Burn Specific Health Scale. The general score of self-esteem of the patients with mild burns( 183+/-23) was obviously lower than that with moderate and severe burns (167+/-21 and 154 +/-24) , ( P <0.01). The self-esteem level of burn patients was different in different sex and education level. Among the self-esteem scores, male burn patients presented evidently higher scores of self evaluation, social ability, appearance, as well as the general score than those in the female ( P < 0.05). Moreover, the self evaluation score and study ability was higher in those with higher education level than those with lower education. Furthermore, the score of social adaptation ability was higher in the patients with mild burns than that in patients with moderate and severe burns ( P < 0. 01). The social adaptation ability and psychological function were much higher in male patients than those in female patients, but the former were weaker than the latter in regard to the body function. The psychological function, social relationship and general condition of the patients with lower education were better than those with higher education ( P <0. 05 ). There existed difference in the self-esteem and social adaptation ability in different burn patients during different periods.


Caveolin-1-dependent beta1 integrin endocytosis is a critical regulator of fibronectin turnover.
beta1 integrins are major cell surface receptors for fibronectin. Some integrins, including beta1 integrins, are known to undergo constitutive endocytosis and recycling. Integrin endocytosis/recycling has been implicated in the regulation of cell migration. However, the mechanisms by which integrin endocytosis/recycling regulates cell migration, and other biological consequences of integrin trafficking are not completely understood. We previously showed that turnover of extracellular matrix (ECM) fibronectin occurs via receptor-mediated endocytosis. Here, we investigate the biological relevance of beta1 integrin endocytosis to fibronectin matrix turnover. First, we demonstrate that beta1 integrins, including alpha5beta1 play an important role in endocytosis and turnover of matrix fibronectin. Second, we show that caveolin-1 constitutively regulates endocytosis of alpha5beta1 integrins, and that alpha5beta1 integrin endocytosis can occur in the absence of fibronectin and fibronectin matrix. We also show that downregulation of caveolin-1 expression by siRNA results in marked reduction of beta1 integrin and fibronectin endocytosis. Hence, caveolin-1-dependent beta1 integrin and fibronectin endocytosis plays a critical role in fibronectin matrix turnover, and may contribute to abnormal ECM remodeling that occurs in fibrotic disorders.


Patterns of tobacco smoking in Australia. 2.
Australian smoking patterns have been surveyed in 1974 and 1976. There appears to be a slight downward trend in male smoking and a slight increase in female smoking. Smoking is more prevalent in the cities than in the country, and among blue collar workers than among white collar workers. Usage of "low tar" cigarettes is also increasing.


A Strategy to Delay the Development of Cisplatin Resistance by Maintaining a Certain Amount of Cisplatin-Sensitive Cells.
Cisplatin (ddp), which is commonly employed in the treatment of many advanced cancers, often results in initial therapeutic success; however, rapid progression of ddp-resistant cells remains the main reason for treatment failure. Facd with such a problem, we investigated the fitness differences between ddp-sensitive and ddp-resistant cell lines. We found that the growth of ddp-resistant cells was significantly slower than that of sensitive cells due to elevated ROS levels, which suggested that the ddp resistance mechanisms may have negative impacts on the growth of resistant cells. Furthermore, we observed that, when mixed with ddp-sensitive cells, ddp-resistant cells failed to compete, and the growth of ddp-resistant cells could therefore be suppressed by treatment in vivo. We propose a mathematical model parameterized based on in vivo experiments to describe the allometric growth of tumors consisting of two competing subclones. According to our model, a quantitative strategy with a variant drug-dosing interval is proposed to control tumor growth. Taking advantage of intratumoral competition, our strategy with appropriate dosing intervals could remarkably delay the development of ddp resistance and prolong overall survival. Maintaining a certain number of ddp-sensitive cells rather than eradicating the tumor with continuous treatment is feasible for future tumor treatment.


[Myocardial Revascularization in Patients With Chronic Ischemic Heart Disease Combined With Chronic Obstructive Pulmonary Disease].
Currently enough data has been accumulated to consider chronic obstructive pulmonary disease (COPD) as one of important factors of poor prognosis in patients with coronary artery disease, possibly producing an impact on perioperative risk during coronary artery bypass grafting surgery and percutaneous coronary interventions, as well as on long-term outcomes of these procedures. In this review we have analyzed studies which attempted to assess COPD as a factor that can affect outcomes of myocardial revascularization.


Nutritional perspectives on sickle cell disease in Africa: a systematic review.
Sickle cell disease (SCD) is an inherited blood disorder that predominantly affects individuals in sub-Saharan Africa. However, research that elucidates links between SCD pathophysiology and nutritional status in African patients is lacking. This systematic review aimed to assess the landscape of studies in sub-Saharan Africa that focused on nutritional aspects of SCD, and highlights gaps in knowledge that could inform priority-setting for future research. The study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Inclusion criteria comprised original, peer-reviewed research published between January 1995 and November 2020 involving individuals in Africa with any phenotypic variant of SCD and at least one nutritional status outcome. Nutritional status outcomes were defined as those that assessed dietary intakes, growth/anthropometry, or nutritional biomarkers. Databases used were Ovid Embase, Medline, Biosis and Web of Science. The search returned 526 articles, of which 76 were included in the final analyses. Most investigations (67%) were conducted in Nigeria. Studies were categorized into one of three main categories: descriptive studies of anthropometric characteristics (49%), descriptive studies of macro- or micronutrient status (41%), and interventional studies (11%). Findings consistently included growth impairment, especially among children and adolescents from sub-Saharan Africa. Studies assessing macro- and micronutrients generally had small sample sizes and were exploratory in nature. Only four randomized trials were identified, which measured the impact of lime juice, long-chain fatty acids supplementation, ready-to-use supplementary food (RUSF), and oral arginine on health outcomes. The findings reveal a moderate number of descriptive studies, most with small sample sizes, that focused on various aspects of nutrition and SCD in African patients. There was a stark dearth of interventional studies that could be used to inform evidence-based changes in clinical practice. Findings from the investigations were generally consistent with data from other regional settings, describing a significant risk of growth faltering and malnutrition among individuals with SCD. There is an unmet need for clinical research to better understand the potential benefits of nutrition-related interventions for patients with SCD in sub-Saharan Africa to promote optimal growth and improve health outcomes.


Disparity refinement framework for learning-based stereo matching methods in cross-domain setting for laparoscopic images.
Stereo matching methods that enable depth estimation are crucial for visualization enhancement applications in computer-assisted surgery. Learning-based stereo matching methods have shown great promise in making accurate predictions on laparoscopic images. However, they require a large amount of training data, and their performance may be degraded due to domain shifts. Maintaining robustness and improving the accuracy of learning-based methods are still open problems. To overcome the limitations of learning-based methods, we propose a disparity refinement framework consisting of a local disparity refinement method and a global disparity refinement method to improve the results of learning-based stereo matching methods in a cross-domain setting. Those learning-based stereo matching methods are pre-trained on a large public dataset of natural images and are tested on two datasets of laparoscopic images. Qualitative and quantitative results suggest that our proposed disparity framework can effectively refine disparity maps when they are noise-corrupted on an unseen dataset, without compromising prediction accuracy when the network can generalize well on an unseen dataset. Our proposed disparity refinement framework could work with learning-based methods to achieve robust and accurate disparity prediction. Yet, as a large laparoscopic dataset for training learning-based methods does not exist and the generalization ability of networks remains to be improved, the incorporation of the proposed disparity refinement framework into existing networks will contribute to improving their overall accuracy and robustness associated with depth estimation.


The status of immunohistochemical studies in lymphoma diagnosis.
Immunohistochemical studies of formalin fixed paraffin embedded sections today constitute an essential component of the diagnostic process for malignant lymphoma. Lineage related markers are of value in distinguishing various lymphomas from anaplastic large and small cell carcinomas, and from sarcomas. Other more recently available markers are of value in establishing prognosis and, on occasion, in differentiating between neoplastic and reactive proliferations. Meticulous attention to reagent control and technical procedures is essential to all such studies.


Influenza activity--United States and worldwide, 2007-08 season.
During the 2007-08 influenza season, influenza activity peaked in mid-February in the United States and was associated with greater mortality and higher rates of hospitalization of children aged 0-4 years, compared with each of the previous three seasons. In the United States, influenza A (H1N1) was the predominant strain early in the season; influenza A (H3N2) viruses increased in circulation in January and predominated overall. While influenza A (H1N1), A (H3N2), and B viruses cocirculated worldwide, influenza A (H1N1) viruses were most commonly reported in Canada, Europe, and Africa, and influenza B viruses were predominant in most Asian countries. This report summarizes influenza activity in the United States and worldwide during the 2007-08 influenza season (September 30, 2007-May 17, 2008).


Integration of neoadjuvant and adjuvant chemotherapy and cystectomy in the treatment of muscle-invasive bladder cancer.
Bladder cancer is a potentially curable malignancy but for those patients who present with or develop muscle-invasive disease, there is a high risk of metastases and cancer-related death. The treatment of patients with muscle-invasive bladder cancer uses a multimodal approach, including radical cystectomy with pelvic lymph node dissection and perioperative chemotherapy. Neoadjuvant cisplatin combination chemotherapy has a modest survival benefit, with those patients achieving a complete pathological response after chemotherapy having the best outcome. Adjuvant chemotherapy, although less well substantiated, is a reasonable option for patients with extravesical disease or lymph node involvement after cystectomy. Perioperative chemotherapy is substantially underused despite the level-1 evidence showing a survival benefit. Ongoing research will focus on individualized patient care, with biomarkers to predict a pathological complete response and the development of novel targeted therapies.


Suppression of allograft rejection by Tim-1-Fc through cross-linking with a novel Tim-1 binding partner on T cells.
Engagement of T-cell immunoglobulin mucin (Tim)-1 on T cells with its ligand, Tim-4, on antigen presenting cells delivers positive costimulatory signals to T cells. However, the molecular mechanisms for Tim-1-mediated regulation of T-cell activation and differentiation are relatively poorly understood. Here we investigated the role of Tim-1 in T-cell responses and allograft rejection using recombinant human Tim-1 extracellular domain and IgG1-Fc fusion proteins (Tim-1-Fc). In vitro assays confirmed that Tim-1-Fc selectively binds to CD4(+) effector T cells, but not dendritic cells or natural regulatory T cells (nTregs). Tim-1-Fc was able to inhibit the responses of purified CD4(+) T cells that do not express Tim-4 to stimulation by anti-CD3/CD28 mAbs, and this inhibition was associated with reduced AKT and ERK1/2 phosphorylation, but it had no influence on nTregs. Moreover, Tim-1-Fc inhibited the proliferation of CD4(+) T cells stimulated by allogeneic dendritic cells. Treatment of recipient mice with Tim-1-Fc significantly prolonged cardiac allograft survival in a fully MHC-mismatched strain combination, which was associated with impaired Th1 response and preserved Th2 and nTregs function. Importantly, the frequency of Foxp3(+) cells in splenic CD4(+) T cells was increased, thus shifting the balance toward regulators, even though Tim-1-Fc did not induce Foxp3 expression in CD4(+)CD25(-) T cells directly. These results indicate that Tim-1-Fc can inhibit T-cell responses through an unknown Tim-1 binding partner on T cells, and it is a promising immunosuppressive agent for preventing allograft rejection.


Subcutaneous use of treprostinil in pediatric pulmonary hypertension patients: A report of three cases.
Treprostinil was approved by the United States Food and Drug Administration for use in the treatment of pulmonary arterial hypertension in 2002. Intravenous or subcutaneous treprostinil is used in pulmonary arterial hypertension patients in the functional classes of II-IV to alleviate exercise-related symptoms, or in cases where epoprostenol treatment should be reduced due to side effects. In this article, we describe three pediatric cases of pulmonary arterial hypertension in whom subcutaneous treprostinil was used.


Atypical teratoid/rhabdoid tumor arising in a malignant glioma.
Atypical teratoid/rhabdoid tumor (AT/RT), a highly malignant brain tumor in young children, usually arises de novo and has only rarely been described as a secondary malignancy. Here, we present a case of a child with glioblastoma, who was treated postoperatively by a combination of temozolomide, irradiation, and bevacizumab. AT/RT was diagnosed as a secondary tumor, 2.5 years following primary diagnosis. The child died 13 months after the diagnosis of AT/RT. This case demonstrates that malignant gliomas may give rise to AT/RT. It also emphasizes the diagnostic value of a repeated tumor biopsy in the recurrence setting.


Conductive Polymer Protonated Nanocellulose Aerogels for Tunable and Linearly Responsive Strain Sensors.
Strong and highly conductive aerogels have been assembled from cellulose nanofibrils (CNFs) protonated with conductive poly(3,4-ethylene dioxythiophene)/poly(styrene sulfonate) (PEDOT/PSS) complex at equal mass or less. Protonating CNF surface carboxylates and hydrogen-bonding CNF surface carboxyls with PSS in PEDOT/PSS generated PEDOT/PSS/CNF aerogels that were up to ten times stronger while as conductive as neat PEDOT/PSS aerogel, attributed to the transformation of PEDOT benzoid structure to the more electron transfer-preferred quinoid structure. Ethylene glycol vapor annealing further increased the conductivity of PEDOT/PSS/CNF aerogels by 2 orders of magnitude. The poly(dimethylsiloxane) (PDMS)-infused conductive PEDOT/PSS/CNF aerogel (70 wt % CNF) transform a resistance-insensitive PDMS-infused PEDOT/PSS aerogel (gauge factor of 1.1 × 10-4) into a stretchable, sensitive, and linearly responsive strain sensor (gauge factor of 14.8 at 95% strain).


New FACTOR IX linked marker alleles in African Haemophilia B patients.
Three markers, one restriction length polymorphism (RFLP) (MseI) and two microsatellite markers (Intron 1 and 3'UTR), linked to the FACTOR IX gene, were assessed for the purpose of genetic testing for Haemophilia B families in South Africa. This was carried out using seven Haemophilia B families and fifty random control samples. We observed five new alleles for the Intron 1 marker within the black control and patient sample groups, and informativity in 89% (8/9) of all carrier females for at least one of the three markers observed. These markers are useful for carrier detection and prenatal diagnosis of Haemophilia B in the great majority of South African black and white families.


Inclusion of soil carbon lateral movement alters terrestrial carbon budget in China.
The lateral movement of soil carbon has a profound effect on the carbon budget of terrestrial ecosystems; however, it has never been quantified in China, which is one of the strongest soil erosion areas in the world. In this study, we estimated that the overall soil erosion in China varies from 11.27 to 18.17 Pg yr(-1) from 1982 to 2011, accounting for 7-21% of total soil erosion globally. Soil erosion induces a substantial lateral redistribution of soil organic carbon ranging from 0.64 to 1.04 Pg C yr(-1). The erosion-induced carbon flux ranges from a 0.19 Pg C yr(-1) carbon source to a 0.24 Pg C yr(-1) carbon sink in the terrestrial ecosystem, which is potentially comparable in magnitude to previously estimated total carbon budget of China (0.19 to 0.26 Pg yr(-1)). Our results showed that the lateral movement of soil carbon strongly alters the carbon budget in China, and highlighted the urgent need to integrate the processes of soil erosion into the regional or global carbon cycle estimates.


Evolutionary Fates and Dynamic Functionalization of Young Duplicate Genes in Arabidopsis Genomes.
Gene duplication is a primary means to generate genomic novelties, playing an essential role in speciation and adaptation. Particularly in plants, a high abundance of duplicate genes has been maintained for significantly long periods of evolutionary time. To address the manner in which young duplicate genes were derived primarily from small-scale gene duplication and preserved in plant genomes and to determine the underlying driving mechanisms, we generated transcriptomes to produce the expression profiles of five tissues in Arabidopsis thaliana and the closely related species Arabidopsis lyrata and Capsella rubella Based on the quantitative analysis metrics, we investigated the evolutionary processes of young duplicate genes in Arabidopsis. We determined that conservation, neofunctionalization, and specialization are three main evolutionary processes for Arabidopsis young duplicate genes. We explicitly demonstrated the dynamic functionalization of duplicate genes along the evolutionary time scale. Upon origination, duplicates tend to maintain their ancestral functions; but as they survive longer, they might be likely to develop distinct and novel functions. The temporal evolutionary processes and functionalization of plant duplicate genes are associated with their ancestral functions, dynamic DNA methylation levels, and histone modification abundances. Furthermore, duplicate genes tend to be initially expressed in pollen and then to gain more interaction partners over time. Altogether, our study provides novel insights into the dynamic retention processes of young duplicate genes in plant genomes.


Optimizing the treatment of bevacizumab as first-line therapy for human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer: an updated meta-analysis of published randomized trials.
Manifold data have demonstrated that the addition of bevacizumab to chemotherapy improved progression-free survival (PFS), while few trials have revealed its significant overall survival (OS) benefit. Furthermore, it still remains suspended how to maximize the benefits of bevacizumab as first-line therapy for human epidermal growth factor receptor 2 (HER2)-negative breast cancer. We sought to conduct a meta-analysis to assess the benefits of bevacizumab with chemotherapy and to identify the ideal chemotherapy partner of bevacizumab in the first-line setting for HER2-negative advanced breast cancer patients. Computerized and manual searches were performed to identify randomized clinical trials evaluating the efficacy of bevacizumab plus chemotherapy versus chemotherapy alone or bevacizumab with different chemotherapy regimens as first-line therapy for HER2-negative locally recurrent or metastatic breast cancer patients. Risk ratios or odds ratios with their 95% CIs were used to estimate the association between multiple combinations of bevacizumab with chemotherapy and various clinical outcomes. With 7 trials identified, this analysis included 3,984 eligible patients. The addition of bevacizumab to chemotherapy resulted in a statistically significant improvement in PFS (P=0.019) and objective response rate (ORR; P<0.001) rather than in OS (P=0.783) when compared with chemotherapy alone. The greater benefits in PFS and ORR were achieved from bevacizumab plus taxane-based regimens compared with bevacizumab plus capecitabine-based regimens, while bevacizumab plus capecitabine had comparable OS with bevacizumab plus paclitaxel. Additionally, bevacizumab-based triplet therapy failed to improve the clinical outcomes when compared with doublet therapy. This meta-analysis reveals that the addition of bevacizumab to chemotherapy yielded PFS and ORR benefits in HER2-negative advanced breast cancer. Additional studies are still prompted to further optimize the first-line treatment of bevacizumab.


28-year late spermatic cord relapse of a testicular non-seminomatous germ cell tumour, managed robotically.
We present a patient who relapsed symptomatically 28 years post-orchiectomy, initially followed by active surveillance for clinical stage I non-seminomatous germ cell tumour (CSI NSGCT). His relapse was localized to the pelvis, managed with robotic surgery, and achieved a complete resection with tumour markers normalized. We highlight the current Princess Margaret guidelines for followup of CSI NSGCT and discuss the trade-off between lifelong radiographic surveillance to detect the very small risk of late relapse. We discuss the incidence and presentation of late relapse, treatment options, and outcomes, highlighting that these tumours are typically refractory to chemotherapy and can often be managed with surgery alone.


[Adaptive repetitive control of wrist tremor suppression based on functional electrical stimulation].
Tremor is an involuntary and repetitive swinging movement of limb, which can be regarded as a periodic disturbance in tremor suppression system based on functional electrical stimulation (FES). Therefore, using repetitive controller to adjust the level and timing of FES applied to the corresponding muscles, so as to generate the muscle torque opposite to the tremor motion, is a feasible means of tremor suppression. At present, most repetitive control systems based on FES assume that tremor is a fixed single frequency signal, but in fact, tremor may be a multi-frequency signal and the tremor frequency also varies with time. In this paper, the tremor data of intention tremor patients are analyzed from the perspective of frequency, and an adaptive repetitive controller with internal model switching is proposed to suppress tremor signals with different frequencies. Simulation and experimental results show that the proposed adaptive repetitive controller based on parallel multiple internal models and series high-order internal model switching can suppress tremor by up to 84.98% on average, which is a significant improvement compared to the traditional single internal model repetitive controller and filter based feedback controller. Therefore, the adaptive repetitive control method based on FES proposed in this paper can effectively address the issue of wrist intention tremor in patients, and can offer valuable technical support for the rehabilitation of patients with subsequent motor dysfunction.


Predictors of condom use among sexually active persons involved in compulsory national service in Ibadan, Nigeria.
Migration is known to increase the risk of heterosexual transmission of human immunodeficiency virus (HIV) in sub-Saharan Africa, but little attention has been paid to fresh graduates of tertiary institutions who are on migration for compulsory national assignment in Nigeria. In July and August 2004, a survey was conducted on sexually active men (n = 344) and women (n = 373) to investigate determinants of condom use during national service. Sixty-eight percent of men and 41% of women reported condom use at last intercourse before the survey. For both men and women, condom use was common if they had one or more regular sex partners and if they were purchasing condoms. In addition, women's condom use was predicted by being single and having intention to use condoms in next intercourse. The findings further showed that there was high risk of HIV transmission in the sample population as consistent condom use was 15% for men and 4% for women. Twelve percent of men and 8% of women reported STI diagnoses in the last 12 months before the survey. Four percent of men and 2% of women reported they already had HIV diagnoses. Only 1% of men and 2% of women reported they would receive voluntary HIV test if offered free by the government. The study findings suggest the need to extend the existing condom social marketing services in the country to the youth on national service and promote condom education messages among them prior to commencing national service.


Role of oral propranolol in the treatment of infantile subglottic hemangioma.
To determine the efficacy of oral propranolol for the treatment of infantile subglottic hemangioma. 17 children (13 females and 4 males) with a median age at onset of treatment of 5 months were included in this study. Propranolol was administered after the presence of subglottic hemangioma was confirmed by laryngoscopy and a CT scan of the trachea with contrast. Propranolol was started at 1 mg/kg per day divided into 3 doses. Heart rate and blood pressure were monitored during treatment. If no side effects were observed, then the dose was increased to 1.5 mg/kg per day on the second day. 14 patients (82%) showed clinical improvement within 1 week of treatment initiation. In each of these patients, the diameter of the subglottic stenosis caused by the hemangioma decreased, and the hemangioma became lighter in color. Two children with cutaneous hemangiomata also exhibited significant improvements in their cutaneous lesions after treatment. One patient's treatment was stopped after 2 weeks for personal reasons (family issue). After treatment cessation, this patient's respiratory symptoms recurred and increased in severity over the next 2 weeks. The patient was restarted on propranolol, and the symptoms disappeared. One patient only partially responded to propranolol. One patient continued with a tracheostomy for 15 months due to the diffuse nature of the lesion and was just recently decannulated. One patient initially did not respond to propranolol and developed residual disease after open resection; this patient finally responded to propranolol after 6 months of therapy and was recently weaned off the drug. Oral propranolol is a safe and effective treatment for infantile subglottic hemangiomata and may be used as a first-line therapeutic modality.


Familial association of neuropsychological traits in patients with generalized and partial seizure disorders.
To investigate familial effects of neuropsychological deficits associated with seizure disorders, we studied 65 families, in which 1 member had epilepsy. The disorders included childhood absence epilepsy (CAE), juvenile myoclonic epilepsy (JME) and temporal lobe epilepsy (TLE). Age-appropriate tests were administered to assess sustained attention, encoding and verbal memory, executive and focused attention and attentional flexibility/impulsivity. CAE probands attained lower scores than other probands in visual sustained attention and the ability to focus on and execute a visual-motor task. Scores of the unaffected relatives tended to fall between those of the probands and the controls. JME relatives had lower scores than other relatives in tests of visual and auditory sustained attention and attentional flexibility, and showed greater variability in response time. Behavioral information of this type may aid in the specification and differentiation of genetic linkages in affected families.


Vascular Lipidomic Profiling of Potential Endogenous Fatty Acid PPAR Ligands Reveals the Coronary Artery as Major Producer of CYP450-Derived Epoxy Fatty Acids.
A number of oxylipins have been described as endogenous PPAR ligands. The very short biological half-lives of oxylipins suggest roles as autocrine or paracrine signaling molecules. While coronary arterial atherosclerosis is the root of myocardial infarction, aortic atherosclerotic plaque formation is a common readout of in vivo atherosclerosis studies in mice. Improved understanding of the compartmentalized sources of oxylipin PPAR ligands will increase our knowledge of the roles of PPAR signaling in diverse vascular tissues. Here, we performed a targeted lipidomic analysis of ex vivo-generated oxylipins from porcine aorta, coronary artery, pulmonary artery and perivascular adipose. Cyclooxygenase (COX)-derived prostanoids were the most abundant detectable oxylipin from all tissues. By contrast, the coronary artery produced significantly higher levels of oxylipins from CYP450 pathways than other tissues. The TLR4 ligand LPS induced prostanoid formation in all vascular tissue tested. The 11-HETE, 15-HETE, and 9-HODE were also induced by LPS from the aorta and pulmonary artery but not coronary artery. Epoxy fatty acid (EpFA) formation was largely unaffected by LPS. The pig CYP2J homologue CYP2J34 was expressed in porcine vascular tissue and primary coronary artery smooth muscle cells (pCASMCs) in culture. Treatment of pCASMCs with LPS induced a robust profile of pro-inflammatory target genes: TNFα, ICAM-1, VCAM-1, MCP-1 and CD40L. The soluble epoxide hydrolase inhibitor TPPU, which prevents the breakdown of endogenous CYP-derived EpFAs, significantly suppressed LPS-induced inflammatory target genes. In conclusion, PPAR-activating oxylipins are produced and regulated in a vascular site-specific manner. The CYP450 pathway is highly active in the coronary artery and capable of providing anti-inflammatory oxylipins that prevent processes of inflammatory vascular disease progression.


Sports medicine emergencies.
With the high interest in fitness and sporting activities at present, all primary care physicians must be prepared to treat emergencies in sports medicine. Basic knowledge, reference material, equipment, and supplies are mandatory (see Tables 1 and 2). Unique situations may require additional items.


Giant Blistering of Nanometer-Thick Al2O3/ZnO Films Grown by Atomic Layer Deposition: Mechanism and Potential Applications.
Giant circular blisters of up to 300 μm diameter and 10 μm deflection have been produced on nanometer-thick Al2O3-on-ZnO stacks grown by atomic layer deposition at 150 °C followed by annealing at elevated temperatures. Their shape changes upon varied ambient pressures provide evidence that their formation is related to an anneal-induced outgassing combined with their impermeability. The former mainly occurs in the bottom ZnO layer that recrystallizes and releases residual hydroxide ions at elevated temperatures while the latter is dominantly contributed by the pinhole-free Al2O3 layer on top. Vibrations at a resonant frequency of ∼740 kHz are mechanically actuated and optically probed from an individual blister. By modulating the thickness and stacking sequence of Al2O3 and ZnO, we further demonstrate a localized circular film swelling upon electron-beam irradiation and its recovery after reducing the irradiation flux. The elastic blistering and the recoverable swelling of the nanometer-thick films represent a miniaturized event-driven mechanical system for potential functioning applications.