Global variation and outcomes of expectant management of CSP.
The incidence of Cesarean scar pregnancies (CSPs) is rising globally. Ultrasound criteria for the diagnosis of CSPs have been described by the International Society of Ultrasound in obstetrics and gynecology and appear to be well used in various centers around the world. There is no guidance on best practices for expectant management of CSP, and there is considerable variation in how this is offered globally. Many studies have reported significant maternal morbidity in cases of CSP with fetal cardiac activity managed expectantly, largely relating to hemorrhage and cesarean hysterectomy from placenta accreta spectrum. However, high live birth rates are also reported. Literature describing the diagnosis and expectant management of CSP in low-resource settings is lacking. Expectant management in selected cases where no fetal cardiac activity is present is a reasonable option and can be associated with good maternal outcomes. Standardization in reporting different types of CSPs and correlating these with pregnancy outcomes will be an important next step in developing guidance for expectant management of this high-risk pregnancy with a high burden of complications.


A novel bacterial combination for efficient degradation of polystyrene microplastics.
This study aimed to investigate the combined decomposition of polystyrene (PS) microplastics using three bacterial cultures: Stenotrophomonas maltophilia, Bacillus velezensis, and Acinetobacter radioresistens. The ability of all three strains to grow on medium containing PS (Mn 90,000 Da, Mw 241,200 Da) microplastics as the sole carbon source was examined. After 60 days of A. radioresistens treatment, the maximum weight loss of the PS microplastics was found to be 16.7 ± 0.6% (half-life 251.1 d). After 60 days of treatment with S. maltophilia and B. velezensis, the maximum weight loss of PS microplastics was 43.5 ± 0.8% (half-life 74.9 d). After 60 days of treatment with S. maltophilia, B. velezensis, and A. radioresistens, the weight loss of the PS microplastics was 17.0 ± 0.2% (half-life 224.2 d). The S. maltophilia and B. velezensis treatment showed a more significant degradation effect after 60 days. This result was attributed to interspecific assistance and interspecific competition. Biodegradation of PS microplastics was confirmed using scanning electron microscopy, water contact angle, high-temperature gel chromatography, Fourier transform infrared spectroscopy and thermogravimetric analysis. This study is the first to explore the degradation ability of different bacterial combinations on PS microplastics, providing a reference for future research on the biodegradation technology of mixed bacteria.


Protein tyrosine phosphatase epsilon activates Yes and Fyn in Neu-induced mammary tumor cells.
The receptor-type form of protein tyrosine phosphatase epsilon (RPTP) is among the few tyrosine phosphatases that can support the transformed phenotype of tumor cells. Accordingly, cells from mammary epithelial tumors induced by activated Neu in mice genetically lacking RPTP appear morphologically less transformed and exhibit reduced proliferation. The effect of RPTP in these cells is mediated at least in part by its ability to activate Src, the prototypic member of a family of related kinases. We show here that RPTP is a physiological activator of two additional Src family kinases, Yes and Fyn. Activities of both kinases are inhibited in mammary tumor cells lacking RPTP, and phosphorylation at their C-terminal inhibitory tyrosines is increased. In agreement, opposite effects on activities and phosphorylation of Yes and Fyn are observed following increased expression of PTP. RPTP also forms stable complexes with either kinase, providing physical opportunity for their activation by RPTP. Surprisingly, expression of Yes or of Fyn does not rescue the morphological phenotype of RPTP-deficient tumor cells in contrast with the strong ability of Src to do so. We conclude that RPTP activates Src, Yes, and Fyn, but that these related kinases play distinct roles in Neu-induced mammary tumor cells.


[Progress of research on polymorphisms of common drug metabolism related genes among various populations in China].
Genetic background can lead to differences in drug effects among different populations when they use the same drug. To delineate the pharmacogenomics and population genetic differences may help to clarify the role of polymorphisms of drug metabolism-related genes in drug effect heterogeneity among different populations. This article has summarized the latest progress on the polymorphisms of drug metabolism-related genes among different populations in China.


The reversal of paraquat-induced mitochondria-mediated apoptosis by cycloartenyl ferulate, the important role of Nrf2 pathway.
In this study, we demonstrate the protective effects of Cycloartenyl ferulate (CF) against Paraquat (PQ)-induced cytotoxicity and elucidate the underlying molecular mechanisms. The results show that, CF could reverse the PQ-induced growth inhibition and release of lactate dehydrogenase in HK-2 human proximal tubular cells. Treatment with PQ induced apoptosis in HK-2 cells, as evidenced by accumulation of sub-G1 cell population, chromatin condensation, DNA fragmentation, and translocation of phosphatidylserine, which were significantly attenuated by co-incubation with CF. Mitochondria-mediated apoptosis pathway contributed importantly to PQ-induced apoptosis, as revealed by the activation of caspase-3/-9, cleavage of PARP, depletion of mitochondrial membrane potential regulated by Bcl-2 family members, and overproduction of reactive oxygen species, which were also effectively blocked by CF. Moreover, treatments of PQ strongly inhibited the expression of Nrf2 and the downstream effectors, HO1 and NQO1. However, co-treatment with CF effectively reversed this action of PQ. Furthermore, silencing of Nrf2 by the siRNA technique significantly blocked the cytoprotective effects of CF against PQ-induced apoptosis, which suggest the important role of Nrf2 signaling pathway an cell apoptosis induced by PQ. Taken together, this study provides a novel strategy for molecular intervention against PQ-induced nephrotoxicity by using phytochemicals.


Prediction and Understanding of Resilience in Albertan Families: Longitudinal Study of Disaster Responses (PURLS) - Protocol.
Exposure to a natural disaster in childhood can have serious, long-lasting consequences, impacting physical and mental health, development, and learning. Although many children experience negative effects after a disaster, the majority do not, and what differentiates these groups is not well understood. Some of the factors that influence disaster-related outcomes in the midst of adversity include parents' mental health, the home environment, and socioeconomic status. Furthermore, genetics has also a role to play in how children respond to stressors. We had the opportunity to conduct a natural experiment of disaster recovery following the Alberta 2013 Flood. This paper presents the detailed protocol on prediction of resilience in Albertan families, and validation with cortisol data. In addition, data collection procedures, developing resiliency screening tools, candidate gene identification, genotyping, DNA methylation, and genomic analyses are described to achieve the research objectives. This study produced new knowledge by using pre- and post-disaster information on children's health and development, including children's genetics and responses to stress. This information has been identified as important to governments and other organizations invested in early child development. Our comprehensive research plan generates evidence that can be mobilized population-based approaches to improve child and family resiliency.


Transient isolated trochlear nerve palsy associated with Rathke's cleft cyst.
We report the case of a 52-year-old woman who developed vertical diplopia of 1-days duration. Neuro-ophthalmological testing revealed left trochlear nerve palsy, and sellar MRI revealed a 1.5 cm-sized pituitary mass lesion, a Rathke's cleft cyst. The diplopia disappeared spontaneously after 6 days.


Characterization of in vivo cross-reactive tumor resistance between two cultured murine colon lines.
Previous comparative investigations of the in vivo biology of two cultured colon tumors of BALB/c origin, C-C26 and C-C36, demonstrated different biologic activities. To elucidate these differences, the immunogenicity of these lines in providing protection to a subsequent challenge with different doses of tumor cells was investigated. Furthermore, the specificity of this protection was evaluated with cross-protection experiments. The findings demonstrate these lines to be immunogenic and suggest the presence of cross-reactive tumor rejection type antigens on these two cultured colon tumor lines. BALB/c mice immunized with these tumors developed resistance to challenge with the same tumor as well as to challenge with the other colon tumor line. Unexpectedly, BALB/c mice immunized with C-C26 cells and challenged with a syngeneic methylcholanthrene-induced sarcoma, Meth A, exhibited partial resistance to this tumor compared to nonimmunized controls. However, mice immunized with C-C36 cells and challenged with Meth A cells supported the same rate of growth of this tumor as unimmunized controls. These results suggest the presence of at least two different cross-reactive tumor rejection antigens. The first antigen appears to be shared between C-C26 and C-C36 cells while the second antigen may be shared between C-C26 and Meth A. Further definition of these putative antigens could provide us with a better understanding for the diagnosis and treatment of colon tumors.


Keyhole retrosigmoid approach for resection of a petro-tentorial meningioma causing trigeminal neuralgia.
Meningiomas involving the tentorium, comprising 3-6 % of all intracranial meningiomas, pose a great challenge for surgical excision due to their proximity to the deep neurovascular structures and complex anatomic boundries [1]. Depending on certain tumor characteristics and other anatomical findings, surgeons may attempt to tackle these lesions through a middle fossa, retrosigmoid or a single or multiple stage combination of approaches [2]. Here, we present a case of a 72-year-old male with severe left sided facial pain secondary to a homogenously enhancing mass arising in the left petro-tentorial junction, causing significant compression of the trigeminal nerve. After failing pharmacological therapy, the patient consented to surgical resection and decompression of the trigeminal nerve via a key hole retrosigmoid approach. This approach provided adequate exposure of the tumor and surrounding neurovascular structures, enabling safe microsurgical removal of the lesion while minimizing the amount of tissue disruption. Due to the small surgical foot print of the approach, the patient was able to be discharge quickly from the hospital with minimal post-surgical pain. We describe the key surgical steps and reconstruction technique.


Color, sensory and physicochemical attributes of beef burger made using meat from young bulls fed levels of licuri cake.
Licuri cake is a biodiesel byproduct and has been tested as an alternative feed additive for use in cattle production. This study analyzed the color, sensory and chemical attributes of burger meat from bovines. Thirty-two young Nellore bulls were used, housed in individual pens and distributed in a randomized experimental design with four treatments: no addition or the addition of 7, 14 or 21% (w/w) licuri cake in the dry matter of the diet. Interactions between the licuri cake level and the physicochemical variables (P > 0.05) were observed. Additionally, an interaction was observed between the licuri cake level and the burger beef color parameter lightness index (L*) (P = 0.0305). The L* value was positively and linearly correlated with the proportion of licuri cake in the diet of young bulls. The level of inclusion of licuri cake did not affect (P > 0.05) the sensory characteristics; the variables were graded between 6 and 7, indicating good overall acceptance. Up to 21% (w/w) licuri cake can be included in the diet of young bulls without negatively impacting on beef burger quality. © 2015 Society of Chemical Industry.


ADAMTS-13 regulates neutrophil recruitment in a mouse model of invasive pulmonary aspergillosis.
Von Willebrand factor (VWF) is secreted as an acute phase protein during inflammation. ADAMTS-13 regulates the size and prothrombotic activity of VWF by it's specific proteolytic activity. To determine the relevance of this regulatory pathway for the innate inflammatory response by polymorphonuclear neutrophils (PMN), we employed a mouse model of invasive pulmonary aspergillosis (IPA) where PMN functionality is crucial for fungal clearance and survival. IPA was induced by intratracheal application of Aspergillus fumigatus (A. fumigatus) conidia in wildtype (129/Sv/Pas) or ADAMTS-13 deficient (Adamts13 -/-) mice. While neutropenic mice developed lethal IPA, all wildtype mice survived the infection. In contrast to wildtype or VWF deficient mice, Adamts13 -/- mice displayed more severe signs of disease with a lethal course in 24% with an increased fungal burden and signs of acute lung injury. Histology sections demonstrated a more pronounced perivascular leukocyte infiltration in support of a dysregulated inflammatory response in Adamts13 -/- mice. Importantly, we observed no general defect in the activation of neutrophil functions in response to conidia or hyphae in vitro. Therefore, we conclude that the proteolytic regulation of VWF by ADAMTS-13 or ADAMTS-13 by itself is an important mechanism to control PMN recruitment in acute inflammatory processes, such as fungal pneumonias.


Raphe magnus-induced descending inhibition of spinal nociceptive neurons is mediated through contralateral spinal pathways in the cat.
In anesthetized cats, extracellular recordings were made from lumbar spinal dorsal horn neurons, driven by noxious radiant skin heating. Heat-evoked responses were inhibited during electrical stimulation in the medullary nucleus raphe magnus (NRM). To identify the spinal pathways mediating this descending inhibition, reversible blocks in the spinal cord white matter were produced by microinjection of the local anesthetic lidocaine. Descending inhibition from the NRM was significantly reduced during blocks in the dorsal and medial, but not ventral parts of the contralateral lateral funiculus (LF). Blocks at any site in the ipsilateral LF failed to affect NRM-induced descending inhibition. These results indicate that NRM-induced inhibition of nociceptive dorsal horn neurons is conveyed primarily in fibers descending in the contralateral spinal white matter.


Prognostic significance of the number of examined lymph nodes in node-negative gastric adenocarcinoma.
In this study, we investigated the prognostic significance of the number of examined lymph nodes in node-negative gastric adenocarcinoma (GC). A total of 1194 node-positive and 1030 node-negative GC patients undergoing potentially curative gastrectomy was enrolled in this study. Patients were stratified into 3 groups according to the number of examined lymph nodes: group 1, ≤ 15; group 2, 16-25; group 3, >25. Patients with node-negative GC had significantly favorable survival compared with those with node-positive. Among patients with node-negative T2-T4 disease, the percentage of locoregional relapse was higher in those with <25 examined lymph nodes than in those with ≥ 25 examined lymph nodes. The number of examined lymph nodes affected the overall survival rates for patients with node-negative T2-T4 GC but not for patients with T1 lesions. Tumor size, tumor location, the number of examined lymph nodes, T status, and the presence of perineural invasion were significant prognostic factors as determined by multivariate analysis in node-negative GC. No survival benefit of examining ≥ 15 lymph nodes was noted for patients with node-negative T1 GC. Extensive lymphadenectomy in patients with node-negative T2-T4 lesions in whom the number of examined lymph nodes was >25 had favorable survival.


Painful conditions around the elbow.
This article discusses the origin and histology of conditions causing pain around the elbow as well as possible treatments. Specific conditions examined include epicondylitis and medial, posterior, and anterior musculotendinous injuries.


Translation-A tug of war during viral infection.
Viral reproduction is contingent on viral protein synthesis that relies on the host ribosomes. As such, viruses have evolved remarkable strategies to hijack the host translational apparatus in order to favor viral protein production and to interfere with cellular innate defenses. Here, we describe the approaches viruses use to exploit the translation machinery, focusing on commonalities across diverse viral families, and discuss the functional relevance of this process. We illustrate the complementary strategies host cells utilize to block viral protein production and consider how cells ensure an efficient antiviral response that relies on translation during this tug of war over the ribosome. Finally, we highlight potential roles mRNA modifications and ribosome quality control play in translational regulation and innate immunity. We address these topics in the context of the COVID-19 pandemic and focus on the gaps in our current knowledge of these mechanisms, specifically in viruses with pandemic potential.


Phosphatidylserine prevents UV-induced decrease of type I procollagen and increase of MMP-1 in dermal fibroblasts and human skin in vivo.
In an effort to find topical agents that prevent or retard cutaneous aging, seven functional lipids were screened for their procollagen-upregulating and matrix metalloproteinase (MMP)-1-downregulating activities in human dermal fibroblasts by Western blotting. The preventive effect on ultraviolet (UV)-induced decrease of procollagen was demonstrated in phosphatidylserine (PS), lysophosphatidylserine (LPS), lysophosphatidic acid (LPA), N-acetyl phytosphingosine (NAPS), and tetraacetyl phytosphingosine (TAPS). Furthermore, PS, LPS, and LPA upregulated procollagen expression in unirradiated basal conditions. The inhibitory effect on UV-induced MMP-1 expression was seen in NAPS, TAPS, LPA, PS, lysophosphatidylglycerol, and LPS. PS was chosen as the most suitable candidate anti-aging chemical for the subsequent in vivo studies. We investigated the effects of PS on acute UV response and chronologic skin aging by topically applying it to young skin before UV irradiation and to aged human skin, respectively. Real-time PCR and Western blot revealed that in the young skin, PS treatment prevented UV-induced reduction in procollagen expression and inhibited UV-induced MMP-1 expression. PS also blocked UV-induced IL-6 and COX-2 gene expression in cultured fibroblasts dose-dependently. In the aged skin, PS caused increased procollagen transcription and procollagen immunostaining in the upper dermis, and a significant decrease in MMP-1 expression at both mRNA and protein levels. These results indicate that topical PS has anti-skin-aging properties and point to the potential use of PS as a therapeutic agent in the prevention and treatment of cutaneous aging.


Factor IX molecular defects in diagnosing hemophilia B: a review.
The past several years have seen an explosive growth in the application of recombinant DNA methods to study the molecular pathology of various inherited disorders. As a consequence, molecular defects responsible for the disease have been identified at the sequence level. In this review, I briefly describe the recent progress in the uses of factor IX gene probes in clinical diagnosis of hemophilia B (Christmas disease) carriers, as well as their use for analyzing the structural gene abnormalities that are responsible for the disease.


Attitudes, beliefs and barriers for adherence to the hyposodic diet in patients with heart failure.
To identify attitudes, beliefs and barriers to adherence to the hyposodic diet in patients with heart failure and associated factors. Cross-sectional study with 41 individuals. The Dietary Sodium Restriction Questionnaire was used. Fisher's test was applied for analysis. Attitudes were based on family and professional relationships; in the beliefs, it was highlighted to believe in the diet to improve health. As barriers, insufficient efforts were found to change the diet and taste of low salt foods. It was associated with adherence among the components factors such as: income, perception of cardiac improvement with the diet, family history of renal and heart failure and family adherence to the diet. The identified attitudes and beliefs refer, respectively, to social relationships and trust in the diet to improve health status. The barriers were: insufficient effort to modify the diet and food palatability. Economic, family and clinical factors were associated with hyposodic adherence.


Oxalates in some Indian green leafy vegetables.
The soluble and total oxalate contents of 11 leafy vegetables grown in India were determined. Spinach, purple and green amaranth and colocasia contained high levels of total oxalates, which ranged from 5,138.0 +/- 37.6 mg/100 g dry matter up to 12,576.1 +/- 107.9 mg/100 g dry matter. Seven other leafy vegetables (curry, drumstick, shepu, fenugreek, coriander, radish and onion stalks) contained only insoluble oxalate, which ranged from 209.0 +/- 5.0 mg/100 g dry matter to 2,774.9 +/-18.4 mg/100 g dry matter. In vitro digestion of the samples showed that the gastric available oxalate was 10% lower than the values obtained from acid extraction and that intestinal available oxalate was 20% lower than the values obtained following hot water extraction. The percentage calcium bound in the insoluble oxalate fraction of the dried leafy vegetables ranged from 3.3% to 86.7% of the total calcium. Addition of four different sources of calcium (low fat milk, whole milk, calcium carbonate and calcium sulphate) resulted in a range of 32-100% reductions of intestinal available oxalate in the mixture.


Flavonoids from Plants to Foods: From Green Extraction to Healthy Food Ingredient.
Research on flavonoids from plant sources is showing growing evidence of the versatile health benefits of flavonoids through in vitro and in vivo studies [...].


Multiple gastrointestinal tract diverticula.
Simultaneous occurrence of gastrointestinal diverticula at multiple sites in a single patient is unusual. We report a patient with a Zenker's, a mid-esophageal, a gastric, and multiple colonic diverticula. The presence of multifocal gastrointestinal diverticula suggests as one possible etiology congenital weaknesses in the bowel wall, since esophageal manometry and histology of a resected diverticulum did not reveal any abnormalities other than gastroesophageal reflux.


Effect of the Lee Silverman Voice Treatment BIG® on motor symptoms in a participant with progressive supranuclear palsy: A case report.
Although the Lee Silverman Voice Treatment BIG® (LSVT BIG®) improves motor symptoms in patients with Parkinson's Disease, no reports exist for patients with Progressive Supranuclear Palsy (PSP). To describe the effect of LSVT BIG® on the motor symptoms of a participant with PSP. The participant was a 74-year-old man with PSP. His goals were to improve limb movement, balance ability, and festinating gait over the 4-week LSVT BIG® program. All assessments of limb movement and balance ability showed improvements after intervention for the limb and gait subsections of the PSP rating scale. Scores improved from 9 to 5, and 8 to 6, respectively for the Unified Parkinson's Disease Rating Scale (UPDRS) Part 3, from 30 to 21 and for the Berg balance scale (BBS), from 45 to 50 points. The improvements in UPDRS Part 3 and BBS exceeded the minimum detectable change values (7-8 and 2 points, respectively). After intervention, improvements in festinating gait and rapid walking pace were noted on the UPDRS Part 3 (2 to 1 point) and 10-meter walk test (1.65 m/s to 1.10 m/s). The intervention was effective for the participant but further studies with diverse populations are needed.


Reduced levels of circulating progenitor cells in juvenile idiopathic arthritis are counteracted by anti TNF-α therapy.
Endothelial progenitor cells (EPC) promote angiogenesis and vascular repair. Though reduced EPC levels have been shown in rheumatoid arthritis, no study has so far evaluated EPCs in children with juvenile idiopathic arthritis (JIA). We aimed to study circulating EPCs in children with JIA, their relation to disease activity, and effects of anti TNF-α treatment. Circulating EPCs were quantified by flow cytometry based on CD34, CD133 and KDR expression in peripheral blood of 22 patients with oligoarticular JIA and 29 age-matched controls. EPCs were re-assessed in children with methotrexate-resistant oligo-extended JIA before and up to 12 month after initiation of anti-TNF-alpha therapy. Plasma concentrations of inflammatory and EPC-regulating factors were measured using a multiplex array. Confocal immunofluorescence was used to demonstrate EPCs in synovial tissues. Children with active JIA showed a significant reduction of relative and absolute counts of circulating progenitor cells and EPCs compared to age-matched healthy controls. CD34(+) cell levels were modestly and inversely correlated to disease activity. A strong inverse correlation was found between serum TNF-α and EPC levels. In 8 patients treated with anti TNF-α agents, the number of EPCs rose to values similar to healthy controls. CD34(+)KDR(+) EPCs were found in the synovial tissue of JIA children, but not in control. Children with JIA have reduced levels of the vasculoprotective and proangiogenic EPCs. While EPCs may contribute to synovial tissue remodelling, EPC pauperization may indicate an excess cardiovascular risk if projected later in life.


Identification and characterization of DcUCGalT1, a galactosyltransferase responsible for anthocyanin galactosylation in purple carrot (Daucus carota L.) taproots.
Purple carrots (Daucus carota ssp. sativus var. atrorubens Alef.) accumulate large amounts of cyanidin-based anthocyanins in their taproots. Cyanidin can be glycosylated with galactose, xylose, and glucose in sequence by glycosyltransferases resulting in cyanidin 3-xylosyl (glucosyl) galactosides in purple carrots. The first step in the glycosylation of cyanidin is catalysis by UDP-galactose: cyanidin galactosyltransferase (UCGalT) transferring the galactosyl moiety from UDP-galactose to cyanidin. In the present study, a gene from 'Deep purple' carrot, DcUCGalT1, was cloned and heterologously expressed in E. coli BL21 (DE3). The recombinant DcUCGalT1 galactosylated cyanidin to produce cyanidin-3-O-galactoside and showed optimal activity for cyanidin at 30 °C and pH 8.6. It showed lower galactosylation activity for peonidin, pelargonidin, kaempferol and quercetin. It accepted only UDP-galactose as a glycosyl donor when cyanidin was used as an aglycone. The expression level of DcUCGalT1 was positively correlated with anthocyanin biosynthesis in carrots. The enzyme extractions from 'Deep purple' exhibited galactosylation activity for cyanidin, peonidin and pelargonidin, while those from 'Kuroda' (a non-purple cultivar) did not.


Combined modality treatment of locally advanced breast cancer: adjuvant combination chemotherapy with and without doxorubicin.
Forty-one women with non-metastatic but locally advanced breast cancer were treated by modified radical or radical mastectomy, and were then randomized to receive one of two adjuvant chemotherapy regimens. Regimen A consisted of 6 months of cyclophosphamide, adriamycin, and fluorouracil (CAF) followed by 6 months of cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP). Regimen B was 12 months of CMFVP. Patients were stratified for estrogen-receptor status, and all patients with a positive estrogen receptor value received tamoxifen 20 mg bid in addition to the chemotherapy. Eight of 21 patients randomized to Regimen A are alive and free of disease, whereas only 1 of 20 patients on Regimen B is well. A trend toward improved disease-free survival favoring Regimen A was observed (P = .05), although a significant difference in overall survival has not been demonstrated. Our findings support the continued study of adriamycin-containing regimens in the adjuvant setting and in combined modality therapy of locally advanced breast cancer.


Evaluation of an automated extraction system in combination with Affigene CMV Trender for CMV DNA quantitative determination: comparison with nested PCR and pp65 antigen test.
CMV viral load quantitation is a powerful tool to assist clinicians in making accurate diagnoses, managing post-transplant CMV disease and monitoring antiviral therapy. The aim of this study was to evaluate the performance of Affigene CMV Trender for CMV viral load determination used in combination with a non-dedicated nucleic acid extraction system (BioRobot MDx) for high-throughput routine. Linearity, reproducibility and sensitivity were examined. Clinical samples were used to compare results obtained with the Affigene CMV Trender, with an "in house" nested PCR used for routine diagnosis and with pp65 antigenemia. The results indicated that the test is linear in the range of 1.81-5.18 Logcopies/ml and that sensitivity is 77 copies/ml. The concordance of the Affigene CMV Trender with nested PCR was high, (k=0.91, IC 95%=0.82-1.00), whereas a substantial concordance with pp65 antigenemia was observed (k=0.64, IC 95%=0.54-0.73). In conclusion, combined use of a non-dedicated automated nucleic acid extraction method with the Affigene CMV Trender results in an accurate high throughput system, suitable for routine laboratory monitoring of CMV infection.


Postmenopausal hormone replacement therapy: ovarian cancer.
About 1 additional ovarian cancer per 1000 women exposed to post- menopausal hormone replacement therapy for 5 years.


Inhibition of spontaneous acetylcholine secretion by 2-chloroadenosine as revealed by a protein kinase inhibitor at the mouse neuromuscular junction.
1. Previous studies have reported discrepancies in the potencies of A(1) adenosine receptor agonists at mouse motor nerve terminals. In addition, conflicting results on the role of protein kinase A (PKA) in mediating the inhibitory effects of A(1) receptor agonists have been published. We thus decided to investigate the possibility of endogenous control of adenosine receptor sensitivity by protein kinases, using a variety of protein kinase inhibitors in conjunction with the adenosine receptor agonist 2-chloroadenosine (CADO). 2. CADO, at the concentration employed previously to study spontaneous ACh release in the mouse (1 microM), did not inhibit spontaneous ACh release in our experiments. However, a higher concentration of CADO (10 microM) produced highly statistically-significant reductions in spontaneous ACh release. 3. In the presence of the non-selective protein kinase inhibitor, H7 (50 microM), the potency of CADO was increased such that 1 microM CADO now reduced spontaneous quantal ACh release to approximately 63% of control. 4. Both H7, and the selective PKA inhibitor, KT5720 (500 nM) prevented increases in ACh release produced by CPT cyclic AMP (250 microM), suggesting these kinase inhibitors were blocking PKA. In contrast to H7, however, KT5720, did not reveal an inhibitory effect of 1 microM CADO. A number of other non-selective PKA inhibitors also failed to increase the potency of CADO. 5. The results suggest that an endogenous H7-sensitive process modulates the sensitivity of the mouse A(1) adenosine receptor and that the inhibitory effects of CADO are independent of cyclic AMP accumulation or PKA inhibition.


Bronchoconstriction caused by Florida red tide toxins.
T17, a toxin purified from laboratory cultures of Florida's redtide organism, Ptychodiscus brevis (formerly Gymnodinium breve), produces bronchoconstriction in anesthetized artificially-ventilated guinea pigs. Bronchoconstriction, measured as a resistance to mechanical pulmonary inflation, was antagonized by atropine, but not by interruption of vagal nerve stimulation or diaphragm dissection.


A domain swapping approach to elucidate differential regiospecific hydroxylation by geraniol and linalool synthases from perilla.
Geraniol and linalool are acyclic monoterpenes found in plant essential oils that have attracted much attention for their commercial use and in pharmaceutical studies. They are synthesized from geranyl diphosphate (GDP) by geraniol and linalool synthases, respectively. Both synthases are very similar at the amino acid level and share the same substrate; however, the position of the GDP to which they introduce hydroxyl groups is different. In this study, the mechanisms underlying the regiospecific hydroxylation of geraniol and linalool synthases were investigated using a domain swapping approach and site-directed mutagenesis in perilla. Sequences of the synthases were divided into ten domains (domains I to IV-4), and each corresponding domain was exchanged between both enzymes. It was shown that different regions were important for the formation of geraniol and linalool, namely, domains IV-1 and -4 for geraniol, and domains III-b, III-d, and IV-4 for linalool. These results suggested that the conformation of carbocation intermediates and their electron localization were seemingly to be different between geraniol and linalool synthases. Further, five amino acids in domain IV-4 were apparently indispensable for the formation of geraniol and linalool. According to three-dimensional structural models of the synthases, these five residues seemed to be responsible for the different spatial arrangement of the amino acid at H524 in the case of geraniol synthase, while N526 is the corresponding residue in linalool synthase. These results suggested that the side-chains of these five amino acids, in combination with several relevant domains, localized the positive charge in the carbocation intermediate to determine the position of the introduced hydroxyl group.


Stent-Assisted Clip Placement for Complex Internal Carotid Artery Intracranial Aneurysms.
We report two procedures using a stent-assisted microsurgical clip placement to treat complex intracranial aneurysms originating from supraclinoid segment of the internal carotid artery. In both procedures, primary clip placement was considered technically difficult due to either complex morphology or inferior protrusion of aneurysm fundus within the interclinoid space. A nitinol self-expanding stent was placed across the neck of the aneurysm either preoperatively or intraoperatively. Obliteration of aneurysm and patency of the artery was confirmed by angiography after clip placement. Description of an integrated open microsurgical and endovascular approach and review of literature pertaining to considerations for treatment approach are discussed.


Localization of 14-3-3δ/ξ on the neuronal cell surface.
14-3-3 proteins are intracellularly expressed as ubiquitous adaptor proteins. Here, we found localization of 14-3-3δ/ξ on the neuronal cell surface. 14-3-3δ/ξ was identified as a membrane target for 15-deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2). 15d-PGJ2 is a pathological mediator of neurodegenerative diseases including Alzheimer's disease (AD). A causative peptide for AD, amyloid β, is one of binding partner of 14-3-3δ/ξ. Non-permeabilized neurons were used to avoid the intracellular effects of anti-14-3-3δ/ξ antibody in the present study. The plasmalemmal 14-3-3δ/ξ, but not the cytosolic one, was stimulated by its specific antibody, resulting in neuronal cell death. The neurotoxicity of anti-14-3-3δ/ξ antibody was suppressed by an antioxidant, catalase. Catalase prevented neurons from anti-14-3-3δ/ξ antibody-generating neurotoxic H2O2. The neuroprotective effect of catalase was also detected with the post-treatment of neurons after the application of anti-14-3-3δ/ξ antibody. Activation of mitogen-activated protein kinase signaling cascade is a down-stream consequence of H2O2 exposure. A c-Jun N-terminal kinase inhibitor suppressed anti-14-3-3δ/ξ antibody-induced neuronal cell death. To my knowledge, this is the first report that the antibody-stimulated plasmalemmal 14-3-3δ/ξ induced neuronal cell death. Furthermore, H2O2 and JNK contributed to the neurotoxicity of anti-14-3-3δ/ξ antibody as well as those of amyloid β and 15d-PGJ2.


The effect of carbohydrate and marine peptide hydrolysate co-ingestion on endurance exercise metabolism and performance.
The purpose of this study was to examine the efficacy of introducing a fish protein hydrolysate (PEP) concurrently with carbohydrate (CHO) and whey protein (PRO) on endurance exercise metabolism and performance. In a randomised, double blind crossover design, 12 male volunteers completed an initial familiarisation followed by three experimental trials. The trials consisted of a 90 min cycle task corresponding to 50% of predetermined maximum power output, followed by a 5 km time trial (TT). At 15 min intervals during the 90 min cycle task, participants consumed 180 ml of CHO (67 g(.)hr(-1) of maltodextrin), CHO-PRO (53.1 g(.)hr of CHO, 13.6 g(.)hr(-1) of whey protein) or CHO-PRO-PEP (53.1 g(.)hr(-1) of CHO, 11 g(.)hr(-1) of whey protein and 2.4 g(.)hr(-1)of hydrolyzed marine peptides). During the 90 min cycle task, the respiratory exchange ratio (RER) in the CHO-PRO condition was significantly higher than CHO (p < 0.001) and CHO-PRO-PEP (p < 0.001). Additionally, mean heart rate for the CHO condition was significantly lower than that for CHO-PRO (p = 0.021). Time-to-complete the 5 km TT was not significantly different between conditions (m ± SD: 456 ± 16, 456 ± 18 and 455 ± 21 sec for CHO, CHO-PRO and CHO-PRO-PEP respectively, p = 0.98). Although the addition of hydrolyzed marine peptides appeared to influence metabolism during endurance exercise in the current study, it did not provide an ergogenic benefit as assessed by 5 km TT performance.


Derlin-1 and UBXD8 are engaged in dislocation and degradation of lipidated ApoB-100 at lipid droplets.
Apolipoprotein B-100 (ApoB) is the principal component of very low density lipoprotein. Poorly lipidated nascent ApoB is extracted from the Sec61 translocon and degraded by proteasomes. ApoB lipidated in the endoplasmic reticulum (ER) lumen is also subjected to proteasomal degradation, but where and how it dislocates to the cytoplasm remain unknown. In the present study, we demonstrate that ApoB after lipidation is dislocated to the cytoplasmic surface of lipid droplets (LDs) and accumulates as ubiquitinated ApoB in Huh7 cells. Depletion of UBXD8, which is almost confined to LDs in this cell type, decreases recruitment of p97 to LDs and causes an increase of both ubiquitinated ApoB on the LD surface and lipidated ApoB in the ER lumen. In contrast, abrogation of Derlin-1 function induces an accumulation of lipidated ApoB in the ER lumen but does not increase ubiquitinated ApoB on the LD surface. UBXD8 and Derlin-1 bind with each other and with lipidated ApoB and show colocalization around LDs. These results indicate that ApoB after lipidation is dislocated from the ER lumen to the LD surface for proteasomal degradation and that Derlin-1 and UBXD8 are engaged in the predislocation and postdislocation steps, respectively.


The outcome of congenital cataract surgery in Kuwait.
Congenital cataract is the most common cause of treatable blindness in children and the outcome of congenital cataract surgery has not been studied in Kuwait, so the purpose of this study is to evaluate the visual outcome and the postoperative complications. Medical records of children who underwent congenital cataract surgery between September 2000 and December 2008 at Al-Bahar Eye Center, Ministry of Health of Kuwait were retrospectively reviewed. In 100 eyes that fill the inclusion criteria visual acuity and postoperative complications were recorded. The mean follow up was 3.9 ± 1.7 years with range from 3 to 6 years. The mean age of congenital/developmental cataract surgery is 8.9 ± 8.7 months for bilateral cases and it was 5.75 ± 4.61 months for unilateral cases. The mean final postoperative BCVA in unilateral cases was 1.0 (20/200) log MAR unit and it was 0.3 (20/40) log MAR unit for the bilateral cases. Four percent of the cases developed postoperative glaucoma and 2% of them developed significant opacification of the posterior capsule. Our findings provide evidence of recent improvement over time in the visual prognosis in bilateral, and to a lesser degree, unilateral cataract, in children in Kuwait.


Validation of the estimated glomerular filtration rate equation for Japanese children younger than 2 years.
We have developed a simple and easy method of estimating the glomerular filtration rate (eGFR) of serum creatinine in Japanese children (eGFRUemura). The eGFR equation is for children aged 2-18 years. Therefore Uemura et al. developed an equation for children younger than 2 years (eGFRunder 2). The aim of the present study was to validate this new equation. We collected the data of 13 patients from previous studies and compared the results of eGFRunder 2, eGFRUemura, and updated eGFR developed by Schwartz (eGFRSchwartz) with measured GFR using mean error (ME), root mean square error (RMSE), P30 and Bland-Altman analysis. The ME of eGFRunder 2, eGFRUemura and eGFRSchwartz were 2.3 ± 15.9, 7.7 ± 14.5, and 16.0 ± 18.2 ml/min/1.73m2, respectively. The RMSEs were 15.5, 15.9, and 49.6, respectively. The P30 values were 76.9%, 76.9%, and 53.8%, respectively. The graph of Bland-Altman bias analysis showed fan-shape. The eGFRunder 2 equation was the most accurate in the three equations. The eGFRunder 2 equation was useful for Japanese children younger than 2 years.


Social capital, social support and perceived stress in college students: The role of resilience and life satisfaction.
The study examined whether online and offline social capital and offline social support are associated with less perceived stress in 403 undergraduate Greek college students through the mediating role of resilience and life satisfaction. Gender differences were also explored. A path analysis explored the relationships among the study variables and multi-group analysis explored gender differences. Perceived stress was predicted indirectly by offline social support and offline bonding social capital through resilience and life satisfaction and directly by online bonding. However, offline bonding was associated with reduced resilience and life satisfaction, whereas social support was associated with increased levels of both. Interestingly, whereas offline bonding was associated with reduced perceived stress through resilience for women, for men it occurred through life satisfaction, and it was primarily resilience for women and life satisfaction for men that predicted reduced perceived stress. It was concluded that different personal ties/relationships are associated with perceived stress through diversified pathways and the pathways are different for men and women. Offline social support between closely tied persons is positively associated and offline bonding is negatively associated with the inner resources for a person to cope with stress, whereas online bonding is beneficial in directly decreasing stress.


SFRR-E Young Investigator AwardeeNOXing out stroke: Identification of NOX4 and 5as targets in blood-brain-barrier stabilisation and neuroprotection.
Stroke is the second leading cause of death with high blood pressure and female gender being the main risk factors. However, only one treatment is available and with many contraindications, which leaves more than 80% of patients untreated. Over a thousand experimental stroke treatments have remained unsuccessful in the clinic. In preclinical research, low reproducibility and publication bias have been suggested as causes of low translatability success. NADPH oxidases might be key players in stroke via their unique role as a major and/or early source of reactive oxygen species (ROS). To clarify the role of the different NOX isoforms (1, 2, 4, and 5) we analysed different KO and KI models. Previous literature claimed a role for NOX2. Using both a meta-analytical and a blinded randomised controlled trial approach, we however find that NOX2 plays only a minor role and publication bias and lack of power perturbed the published literature. We earlier showed a detrimental role of NOX4 in stroke and extend this based on cell-specific KO animals that endothelial but not vascular smooth muscle cells are the major source of NOX4 in stroke. Mice do not express the human NOX5 gene. Using a NOX5 KI model, we show that endothelial NOX5 induces hypertension and increased stroke risk, particularly in females. In human hypertension, NOX5 is upregulated, and women have a higher stroke risk. Thus NOX5 might be a missing link in this context. In conclusion, NOX4 and NOX5, but not NOX2, are promising targets for the development of new neuroprotective therapies for ischemic stroke. A priori power and sample size calculation as well as reporting of also negative data is essential with respect to preclinical validation of therapeutic targets.


Structure-based prediction of transcription factor binding sites using a protein-DNA docking approach.
Accurate identification of transcription factor binding sites is critical to our understanding of transcriptional regulatory networks. To overcome the issue of high false-positive predictions that trouble the sequence-based prediction techniques, we have developed a structure-based prediction method that takes into consideration of interactions between the amino acids of a transcription factor and the nucleotides of its DNA binding sequence at structural level, along with an efficient protein-DNA docking algorithm. The docked structures between a protein and a DNA are evaluated using a knowledge-based energy function, in conjunction with van der Waals energy. Our docking algorithm supports quasi-flexible docking, overcoming a number of limiting issues faced by similar docking algorithms. Our rigid-body docking algorithm is tested on a dataset of 141 nonredundant transcription factor-DNA complex structures. The test results show that 63.1% of the 141 complex structures are reconstructed with accuracies better than 1.0 A RMSDs (root mean square deviation) and 79.4% of the complexes are predicted with accuracies better than 3.0 A RMSDs when using the native DNA structures. Our quasi-flexible docking algorithm, assuming that the DNA structures are not known, is tested on a separate set of 45 transcription factor-DNA complexes, of which 57.8% of the docked complex conformations achieve better than 1.0 A RMSDs while 71.1% of the complexes have RMSDs less than 3.0 A. We have also applied our method to predict the binding motifs of the ferric uptake regulator in E. coli and showed that most of the experimentally identified sites can be predicted accurately.


Psychosocial outcomes and quality of life among school-age survivors of retinoblastoma.
Retinoblastoma is the most common intraocular childhood cancer and is typically diagnosed in young children. With increasing number of survivors and improved medical outcomes, long-term psychosocial impacts need to be explored. Thus, the current study sought to assess functioning in school-aged survivors of retinoblastoma. Sixty-nine survivors of retinoblastoma underwent a one-time evaluation of psychosocial functioning. Survivors (Mage = 10.89 years, SD = 1.07 years; 49.3% male; 56.5% unilateral disease) and parents completed measures of quality of life (QoL; PedsQL) and emotional, behavioral, and social functioning (PROMIS [patient-reported outcome measurement information system] Pediatric Profile, BASC-2 parent report). Demographic and medical variables were also obtained. On the whole, both survivors and caregivers indicated QoL and behavioral and emotional health within the typical range of functioning. Survivors reported better physical QoL compared to both parent report and a national healthy comparison sample, whereas caregivers reported that survivors experienced lower social, school, and physical QoL than a healthy comparison. Regarding behavioral and emotional health, survivors indicated more anxiety than a nationally representative sample. Parents of female survivors endorsed lower adaptive scores than parents of male survivors. Results indicated that survivors of retinoblastoma reported QoL and behavioral and emotional health within normal limits, although parents appear to perceive greater impairment across several assessed domains. Understanding both survivor and parent reports remains important for this population. Future research should explore psychosocial functioning of these survivors as they transition to adolescence and early adulthood, given the increased independence and behavioral and emotional concerns during these developmental periods.


Kinematic analysis of mobile-bearing and fixed-bearing knee prostheses by simulation.
The object of the study was to model fixed-bearing knee prostheses (FBKs) and mobile-bearing knee prostheses (MBKs) during weight-bearing deep knee bends and to analyse and compare the kinematics of the two prosthesis types. To obtain quantitative data, an overall model of a leg was constructed, and this included a three-dimensional model of the tibiofemoral joint and simplified two-dimensional models of the ankle and patellofemoral joint. The simulated movement pattern of the tibiofemoral contact point in the FBK was analysed to show the posterior contact position on the tibia at full extension and anterior translation as the knee was flexed from 30 degrees to 90 degrees. The simulated maximum displacements of the medial and lateral contact positions of the FBK were 5.6 and 6.2 mm, respectively. These results were almost in agreement with experimental studies. Compared with the FBK, the movement pattern of the tibiofemoral contact point in the MBK for the anterior contact position on the tibia at full extension and posterior translation, with respect to the tibia as the knee was flexed, gave results closer to those of the normal knee. The simulated displacements of the medial and lateral contact positions of the MBK with respect to the tibia were 9.0 and 13.0 mm from full extension to 90 degrees flexion, respectively. The difference in the kinematic results between the FBK and the MBK could be accounted for by movement of the insert and the larger force of the posterior cruciate ligament on the MBK.


Abnormal general movements in girls with Rett disorder: the first four months of life.
An apparently normal early development was one of the initial criteria for classical Rett syndrome. However, several investigators considered Rett syndrome to be a developmental disorder manifesting very soon after birth. Videos of 14 infants with Rett disorder were carefully assessed for their spontaneous movements, in particular general movements (GMs), during the first 4 months of life. A detailed analysis clearly demonstrated that none of the infants had normal GMs. However, a specific abnormal GM pattern could not be detected for Rett disorder. The abnormal GMs described here, and their individual developmental trajectories are different from the abnormal GMs described in infants with acquired brain lesion. Our study is the first to apply specific standardised measures of early spontaneous movements to infants with Rett syndrome, proving conclusively that the disorder is manifest within the first weeks of life.


Profile of off-axis higher order aberrations and its variation with time among various refractive error groups.
Peripheral higher order aberrations (HOA) of 646 children at 30° temporal, nasal and inferior visual field were measured under cycloplegia (5 mm pupil diameter) using a commercially available Shack-Hartmann aberrometer in the Sydney Myopia Study [age, 12.7 ± 0.4 years (mean ± standard deviation)] and five years later in the Sydney Adolescent Vascular and Eye Study. At baseline, 176 eyes were emmetropic, 95 were myopic and 375 were hyperopic. Coma, 3rd order and RMS of coma increased with eccentricity for all eyes and no difference was observed for 4th order and RMS of C(4,0) among refractive error groups. More positive C(4,0) was observed for hyperopic eyes at periphery. At follow up, 26% had 'myopic change' and 70% had 'no change' in refractive error. At follow-up, horizontal coma became more negative at nasal field and more positive at temporal field for all eyes. More positive C(4,0) for hyperopic eyes at baseline may indicate variation in optical characteristics of peripheral cornea and crystalline lens. An increase in horizontal coma with time, irrespective of refractive error change, may be attributed to variation in the shape factor of peripheral cornea and crystalline lens and/or misalignment of optical surfaces/components relative to the visual axis (angle kappa) as the eye grows in axial length.


Temperature sensitive self-assembling hydroxybutyl chitosan nanoparticles with cationic enhancement effect for multi-functional applications.
Hydroxybutyl chitosan (HBC) with different degree of substitution (DS) were prepared using a homogeneous reaction system (KOH/urea), which could achieve temperature-dependent reversible morphological transition in aqueous solution. During hydrophobic assembly, amino groups on HBC chains exposed on the surface of nanoparticles formed a poly-cationic structure. The structure of HBCs was characterized by FTIR, 13C NMR, XRD, TGA and rheology. The morphology and assembly mechanism of HBC nanoparticles were studied by TEM, AFM and DLS. Also, the results of coagulation, bacteriostatic, superoxide anion clearance and anionic contaminant removal tests suggested that HBC nanoparticles had excellent flocculation and removal effect of anionic composites. Moreover, the cytocompatibility test indicated that HBC could effectively promote proliferation and division of mouse fibroblast, mouse embryonic fibroblast and rat bone marrow mesenchymal stem cells. These cationic HBC nanoparticles exhibited great potential in multi-functional applications.


Globoid cell leukodystrophy (Krabbe's disease). Metabolic studies with cultured fibroblasts.
Metabolism of tritium-labelled galactosylceramide and lactosylceramide added to the culture medium was examined in cultured skin fibroblasts from 4 patients with globoid cell leukodystrophy (GLD) and 4 control individuals. The uptake of [3H]galactosylceramide and [3H]lactosylceramide by the fibroblasts continued actively at least up to 3 days. Approximately 30--40% of the galactosylceramide, which had been taken up, was released subsequently from the cells in a 4-day period, whereas only 10% of lactosylceramide was released during the same period. The GLD fibroblasts showed no abnormality in the kinetics of the uptake and in the release of these glycosphingolipids which are natural substrates of the beta-galactosidase genetically deficient in the disorder. This finding differs from that reported for fibroblasts from patients with metachromatic leukodystrophy, which showed abnormal accumulation and retention of sulfatide added to the culture media. However, degradation of added galactosylceramide to [3H]galactose by the GLD fibroblasts was only 25% of the control cells, while lactosylceramide was degraded at 70% of the normal rate. These findings are consistent with the known substrate specificities of the two acidic beta-galactosidases in human tissues; galactosylceramide is hydrolyzed almost exclusively by galactosylceramidase, while lactosylceramide can be hydrolyzed by both galactosylceramidase and GM1-ganglioside beta-galactosidase.


Production of highly phosphorylated glycopolymers by expression of R1 in Escherichia coli.
The possible involvement of the starch bound R1 protein from potato (Solanum tuberosum L.) in the phosphorylation of starch was investigated by functional expression and characterisation of R1 in Escherichia coli. By expression of R1 in E. coli it is shown that it is possible to produce glycopolymers, e.g., glycogen, with an increased degree of phosphate substitution. The expression of R1 in E. coli resulted in a sixfold increase in glycogen bound phosphate and in an increased accumulation of glycogen leading to a glycogen excess (gex) phenotype. There was an overall shift in the unit-chain length of the isolated glycogen towards smaller degrees of polymerisation. The pleiotropic effects on the glycogen biosynthetic and amylolytic enzyme activities was investigated and showed an increase in ADPglucose pyrophosphorylase activity, as well as a decrease in exo-amylolytic activity. These results are discussed in relation to starch phosphorylation and a possible role of R1 in this respect.


Effect of inhibiting dolichol phosphate-mannose formation on the biosynthesis of the N-acetylglucosaminylpyrophosphoryl polyprenols by the retina.
Previously (Kean, E.L. (1982) J. Biol. Chem. 257, 7952-7954), it was shown that dolichol phosphate-mannose stimulated the formation of the N-acetylglucosamine-containing mono-, di- and trisaccharide intermediates of the dolichol pathway. Consistent with this activating role, the present report demonstrates that inhibition of the formation of dolichol phosphate-mannose by the antibiotics, showdomycin and diumycin, also blocked the stimulatory phenomenon.


Ontogeny of erythropoietin receptor mRNA expression in various tissues of the foetal and the neonatal pig.
Erythropoietin receptor (EPOR) mRNA expression in liver, spleen, bone marrow and testes of foetal and neonatal pigs was analysed using a real-time RT-PCR assay. The results showed that early in the foetal life, EPOR expression is greatest in the liver. Later in foetal life, the spleen has the greatest expression of EPOR, whereas at 2 weeks after birth, the main expression of EPOR is found in the bone marrow. These findings contradict our earlier hypothesis that erythropoietin (EPO) acting in a paracrine fashion can account for an extensive erythropoiesis at birth, a point of time when plasma EPO concentrations are low. Results presented in the present paper suggest that the spleen or, alternatively, the bone marrow is able to respond to very low concentrations of circulating EPO around the time of birth. The testes were found to express significant amounts of EPOR. Since EPO mRNA has previously been found in the testes, a paracrine function of EPO may exist in this organ.


Social jetlag and dietary intake: A systematic review.
The objective of the current systematic review was to critically review the available evidence regarding the link between social jetlag and diet among the general population using observational studies. Electronic databases, including PubMed, Scopus, and ISI Web of Sciences were searched systematically. We reviewed 348 references, of which 17 studies met inclusion criteria with a total sample size of 28,905. Qualitative analysis indicated a negative association between social jetlag and adherence to healthy eating habits, including a negative association with empirically-derived healthy dietary patterns, Japanese dietary patterns, Baltic Sea dietary patterns, and the Mediterranean diet, as well as a positive association with Meat and Starchy dietary pattern. On the other hand, the findings on the link of social jetlag with food groups and nutrients were mixed and controversial, except for a more consistent increase in sugar-sweetened beverages, total fat, and saturated fat intake. Our results indicate a possible link between social jetlag and dietary intake. Research suggests that individuals experiencing greater social jetlag exhibit reduced adherence to a healthy eating pattern. However, it is important to note that the reported association lacks consensus, emphasizing the need for additional longitudinal studies to gain further insights into this matter."


Comparison of deep neural networks to spatio-temporal cortical dynamics of human visual object recognition reveals hierarchical correspondence.
The complex multi-stage architecture of cortical visual pathways provides the neural basis for efficient visual object recognition in humans. However, the stage-wise computations therein remain poorly understood. Here, we compared temporal (magnetoencephalography) and spatial (functional MRI) visual brain representations with representations in an artificial deep neural network (DNN) tuned to the statistics of real-world visual recognition. We showed that the DNN captured the stages of human visual processing in both time and space from early visual areas towards the dorsal and ventral streams. Further investigation of crucial DNN parameters revealed that while model architecture was important, training on real-world categorization was necessary to enforce spatio-temporal hierarchical relationships with the brain. Together our results provide an algorithmically informed view on the spatio-temporal dynamics of visual object recognition in the human visual brain.


Palliative epilepsy surgery in Aicardi syndrome: a case series and review of literature.
Aicardi syndrome (AS) is a severe neurodevelopmental disorder characterized by the triad of seizures, agenesis of corpus callosum, and chorioretinal lacunae. Seizures in AS are typically frequent, of various types, and refractory to medical therapy. Optimal treatment of seizures in AS remains undetermined. We report a series of four patients with Aicardi syndrome who underwent surgical management of their epilepsy including two with corpus callosotomy (CC) of a partial corpus callosum and three with vagus nerve stimulator implantation. Seizure outcome was variable and ranged from near complete resolution of seizures to worsening of seizure profile. The most favorable seizure outcome was seen in a patient with partial agenesis of the corpus callosum treated with CC. Seizure outcome following CC or vagus nerve stimulation in patients with Aicardi syndrome is variable. Although palliative epilepsy surgery may result in improvement in the seizure profile in some patients, studies on larger patient cohorts are needed to identify the precise role that surgery may play in the multidisciplinary approach to controlling seizures in Aicardi syndrome.


Brain metastases free survival differs between breast cancer subtypes.
Brain metastases (BM) are frequently diagnosed in patients with HER-2-positive metastatic breast cancer; in addition, an increasing incidence was reported for triple-negative tumours. We aimed to compare brain metastases free survival (BMFS) of breast cancer subtypes in patients treated between 1996 until 2010. Brain metastases free survival was measured as the interval from diagnosis of extracranial breast cancer metastases until diagnosis of BM. HER-2 status was analysed by immunohistochemistry and reanalysed by fluorescent in situ hybridisation if a score of 2+ was gained. Oestrogen-receptor (ER) and progesterone-receptor (PgR) status was analysed by immunohistochemistry. Brain metastases free survival curves were estimated with the Kaplan-Meier method and compared with the log-rank test. Data of 213 patients (46 luminal/124 HER-2/43 triple-negative subtype) with BM from breast cancer were available for the analysis. Brain metastases free survival differed significantly between breast cancer subtypes. Median BMFS in triple-negative tumours was 14 months (95% CI: 11.34-16.66) compared with 18 months (95% CI: 14.46-21.54) in HER-2-positive tumours (P=0.001) and 34 months (95% CI: 23.71-44.29) in luminal tumours (P=0.001), respectively. In HER-2-positive patients, co-positivity for ER and HER-2 prolonged BMFS (26 vs 15 m; P=0.033); in luminal tumours, co-expression of ER and PgR was not significantly associated with BMFS. Brain metastases free survival in patients with lung metastases was significantly shorter (17 vs 21 months; P=0.014). Brain metastases free survival in triple-negative breast cancer, as well as in HER-2-positive/ER-negative, is significantly shorter compared with HER-2/ER co-positive or luminal tumours, mirroring the aggressiveness of these breast cancer subtypes.


The CYP74B and CYP74D divinyl ether synthases possess a side hydroperoxide lyase and epoxyalcohol synthase activities that are enhanced by the site-directed mutagenesis.
The CYP74 family of cytochromes P450 includes four enzymes of fatty acid hydroperoxide metabolism: allene oxide synthase (AOS), hydroperoxide lyase (HPL), divinyl ether synthase (DES), and epoxyalcohol synthase (EAS). The present work is concerned with catalytic specificities of three recombinant DESs, namely, the 9-DES (LeDES, CYP74D1) of tomato (Solanum lycopersicum), 9-DES (NtDES, CYP74D3) of tobacco (Nicotiana tabacum), and 13-DES (LuDES, CYP74B16) of flax (Linum usitatissimum), as well as their alterations upon the site-directed mutagenesis. Both LeDES and NtDES converted 9-hydroperoxides of linoleic and α-linolenic acids to divinyl ethers colneleic and colnelenic acids (respectively) with only minorities of HPL and EAS products. In contrast, LeDES and NtDES showed low efficiency towards the linoleate 13-hydroperoxide, affording only the low yield of epoxyalcohols. LuDES exhibited mainly the DES activity towards α-linolenate 13-hydroperoxide (preferred substrate), and HPL activity towards linoleate 13-hydroperoxide, respectively. In contrast, LuDES converted 9-hydroperoxides primarily to the epoxyalcohols. The F291V and A287G mutations within the I-helix groove region (SRS-4) of LuDES resulted in the loss of DES activity and the acquirement of the epoxyalcohol synthase activity. Thus, the studied enzymes exhibited the versatility of catalysis and its qualitative alterations upon the site-directed mutagenesis.


Metallic nanoparticles reduce the migration of human fibroblasts in vitro.
Nanoparticles have extremely wide applications in the medical and biological fields. They are being used in biosensors, local drug delivery, diagnostics, and medical therapy. However, the potential effects of nanoparticles on target cell and tissue function, apart from cytotoxicity, are not completely understood. Thus, the aim of this study was to investigate the in vitro effects of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) on human fibroblasts with respect to their interaction with the extracellular matrix and in cell migration. Immunofluorescence analysis revealed that treatment with AgNPs or AuNPs decreased collagen and laminin production at all the concentrations tested (0.1, 1, and 10 μg/mL). Furthermore, cytofluorometric analysis showed that treatment with AgNPs reduced the percentage of cells expressing the collagen receptor very late antigen 2, α2β1 integrin (VLA-2) and the laminin receptor very late antigen 6, α6β1 integrin (VLA-6). In contrast, AuNP treatment increased and decreased the percentages of VLA-2-positive and VLA-6-positive cells, respectively, as compared to the findings for the controls. Analysis of cytoskeletal reorganization showed that treatment with both types of nanoparticles increased the formation of stress fibres and number of cell protrusions and impaired cell polarity. Fibroblasts exposed to different concentrations of AuNPs and AgNPs showed reduced migration through transwell chambers in the functional chemotaxis assay. These results demonstrated that metal nanoparticles may influence fibroblast function by negatively modulating the deposition of extracellular matrix molecules (ECM) and altering the expression of ECM receptors, cytoskeletal reorganization, and cell migration.


The fatty acids available to wild herbivores from indigenous plants is dependent on both plant species and season.
Considerable evidence shows dietary nutrient variation of human foods, but little data is available for wild animals. Plants are known to be low in total lipid, thus limiting essential fatty acid availability to herbivores. The fatty acid profiles of a range of indigenous Southern African plants were examined. Significant differences were detected, both between species, and within species according to season. No differences related to geographical location were detectable.


Antiviral activity of a thymic factor in experimental viral infections. I. Thymic hormonal effect on survival, interferon production and NK cell activity in Mengo virus-infected mice.
A partially purified thymic factor, thymostimulin (TS), significantly increased the survival rate of adult, immune-intact mice infected with the neurotropic Mengo virus. TS treatment was begun after virus inoculation by daily i.p. injections. In untreated C57BL/6 mice, LD50 was reached with 1 X 10(4) PFU, but 10-fold more virus (i.e., 1 X 10(5) PFU) was needed to reach LD50 in TS-treated animals. TS effect on survival, though, could be observed with several virus doses (1 X 10(3) to 1 X 10(6) PFU) (p less than 0.001). A significant effect on survival was also observed with outbred ICR mice (p less than 0.005). Serum interferon (IFN) levels in the Mengo virus-infected mice were relatively low (average peak 300 U/ml), but were significantly increased (two- to ninefold) in the TS-treated mice. Peak serum levels were reached earlier in TS than in control animals (24 hr and 72 hr, respectively). Both acid-labile and acid-stable type I IFN production were augmented by TS in the Mengo virus-infected mice. Natural killer activity was also enhanced by TS, in particular on the second day after virus inoculation. In addition, MP-virus was used as a second, unrelated virus challenge. This virus caused a nonlethal infection, with relatively high levels of serum IFN (average peak 10,000 U/ml). TS increased IFN levels (two- to eight-fold) also in this challenge system. In conclusion, TS causes a nonspecific enhancement of endogenous production of IFN and has a significant effect on the survival of lethally infected mice. The data indicate a potential application of thymic factors for the treatment of viral infections.


Capillary electrophoresis apparatus equipped with a bioluminescence detector using a batch- or flow-type detection cell.
We developed a capillary electrophoresis (CE) apparatus equipped with a batch- or flow-type bioluminescence (BL) detection cell. Firefly luciferin-luciferase BL reaction was used to analyze samples of nucleotides, such as ATP, dATP, ADP, GTP, UTP, CTP, ITP, and TTP. In the CE apparatus with the batch-type cell, ATP was detected at concentrations of 5-100 microM, while the other nucleotides were not detected at concentrations less than 500 microM. The electropherogram of ATP included two BL peaks; the latter peak showed peculiar broadening, which continued up to ca. 2.5 h. In the CE apparatus with the flow-type cell, ATP, dATP, and ADP were detected with single peaks with detection limits of 1, 75, and 100 microM, respectively. The other nucleotides, GTP, UTP, CTP, ITP, and TTP, were not detected at concentrations less than 0.5 mM. A mixture of 10 microM ATP and 100 microM dATP was examined using the CE apparatus with the flow-type BL detection cell. ATP and dATP were separated using running buffer at pH 10 containing 1 mM phenylboronic acid. The interaction between ATP and phenylboronic acid delayed the migration time of ATP.


Infliximab therapy in Crohn's disease: a pragmatic approach?
Infliximab is recognized as an effective therapy in unresponsive luminal and fistulating Crohn's disease. The use of maintenance or 'on demand' therapy thereafter is controversial. To assess the need for maintenance infliximab therapy in a clinical setting where immunomodulatory agents are widely used and where episodic therapy is used in preference to maintenance therapy. Ninety-three patients with Crohn's disease receiving infliximab; 72 with unresponsive luminal disease and 21 with fistulous disease. Data collected included disease site and duration, surgical and smoking history, initial response rates, duration of response maintenance and concomitant medications. Fifty-six of 72 (78%) patients with luminal disease and 11 of 21 (52%) with fistulous disease achieved an initial response. Ten of 67 responders required conversion to maintenance infliximab infusions, while 31 remain in remission. Patients with luminal disease and those who had not taken previous surgery had higher response rates to infliximab. Younger patients and those with small bowel disease had higher relapse rates following initial response. Three patients developed allergic reactions to infliximab and one patient died of progressive pulmonary disease 6 weeks after their first infusion. Many patients with Crohn's disease can be maintained successfully with an episodic infliximab regimen.


Labeling of cholesterol with filipin in cellular membranes of parenchymatous organs. Standardization of incubation conditions.
Filipin is used for ultrastructural cytochemical localization of cholesterol in biological membranes. It binds to unesterified 3 beta-hydroxy-sterols forming 25 nm complexes which are readily recognized in freeze-fracture replicas. Since most investigations with filipin have been performed in isolated cells (tissue culture, cell suspensions etc.) we have investigated the conditions for reproducible labeling of cholesterol in membranes of parenchymatous organs. Vibratome sections of rat kidney fixed by glutaraldehyde perfusion were incubated in filipin and freeze-fracture replicas were prepared using standard techniques. The concentration of filipin, the thickness of vibratome sections and the incubation time and temperature were varied over a wide range. Optimal results were obtained with 50 micron thick tissue slices incubated in 400 micrograms/ml of filipin for 46 h at room temperature. Under these conditions lysosomes were consistently labeled while mitochondria and the endoplasmatic reticulum were negative. Peroxisomes showed a little or no labeling at all while the nuclear envelope was heavily labeled in some cells being negative in others. The method described here should be useful in investigation of the role of cholesterol in function of biological membranes in parenchymatous organs and compact tissues.


High live birth rate in the subsequent IVF cycle after first-cycle poor response among women with mean age 35 and normal FSH.
Poor ovarian response in IVF cycles is associated with diminished ovarian reserve and poor pregnancy outcome. Little is known about pregnancy outcome after a poor response in women with a normal ovarian reserve. This retrospective study studied women undergoing IVF/intracytoplasmic sperm injection between January 2003 to December 2008 in the FertilityPLUS Clinic in Auckland, New Zealand. All women with a poor response in the first cycle were selected. Primary outcome was live birth after the second cycle. Secondary outcomes were poor response in the second cycle and the predictive values of female age and basal FSH at first cycle and IVF outcome at second cycle. Of the 2487 women starting IVF, 142 women (5.7%) with a poor response in the first cycle were selected, of which 66 (46.5%) women had a repeated poor response in the second cycle. There were 31 live births in the second cycle (21.8%). Female age was the only significant predictor for repeated poor response (AUC 0.69, 95% CI 0.61-0.78) and clinical pregnancy (AUC 0.66, 95% CI 0.57-0.75), but the predictive value was low. Therefore poor response in women with a normal ovarian reserve should not be a reason to discontinue further IVF treatment. Poor ovarian response in IVF cycles is associated with diminished ovarian reserve and poor pregnancy outcome. Little is known about pregnancy outcome after a poor response in women with a normal ovarian reserve. In this retrospective study, we studied women undergoing IVF/intracytoplasmic sperm injection (ICSI) between January 2003 to December 2008 in the FertilityPLUS Clinic in Auckland, New Zealand. All women with a poor response in the first cycle were selected. Primary outcome was live birth after the second cycle. Secondary outcomes were poor response in the second cycle and the predictive value of female age and basal FSH at first cycle and IVF outcome at the second cycle. Of the 2487 women starting wit IVF, a total of 142 women (5.7%) with a poor response in the first cycle were selected, of which 66 (46.5%) women had a repeated poor response in the second cycle. There were 31 live births in the second cycle (22%). Female age was the only significant predictor for repeated poor response and clinical pregnancy, but the predictive value was low. Therefore poor response in women with a normal ovarian reserve should not be a reason to discontinue further IVF treatment.


Introduction: The Multidisciplinary Team Approach to Burn Care.
Since the first burn units were established following World War II, great advances in understanding and treating burn shock, smoke inhalation injury, pneumonia, and invasive burn wound infections, and in achieving early burn-wound closure, have greatly decreased postburn morbidity and mortality. These advances were the result of closely integrated multidisciplinary teams of clinicians and researchers. The team approach to burns is a model for success in the care of any challenging clinical problem.


First record of Gnathia sp. an ectoparasitic isopod isolated from the coral reef fish, Heniochus acuminatus collected from the Gulf of Mannar region, southeast coast of India.
An ectoparasitic isopod, Gnathia sp. was found in the Gill chambers of Heniochus acuminatus collected from the Gulf of Mannar region, Southeast coast of India. The present study signifies the new record of Gnathia sp. an coral reef ectoparasitic isopod captured from the gill net during October 2014. Among the 36 specimens examined 5 specimens were infested with Pranzia larvae of Gnathia sp. The size of the isopods were ranged from 1.5 to 3.2 mm and the host fish length varied between 119 and 230 mm. They were specifically found attached to the gill chambers and no damage observed in the lamellar pattern.


Trends in the inequality of fruit and vegetable consumption between education levels indicated by the Korea National Health and Nutrition Examination Surveys.
The objective of this study was to investigate whether an inequality in fruit and/or vegetable (FV) consumption exists between adults of different educational levels in Korea and whether this has changed over the past decade. This study included adults ≥ 20 years) who participated in the Korea National Health and Nutrition Examination Survey (1998-2009). The FV intakes were examined using 24-h dietary-recall surveys (n=35,725) and food frequency questionnaires (n=35,400). The relative index of inequality (RII) was used to examine the magnitude and trend of inequality in insufficient FV intake (<500 gram/day for total FV; <100 gram/day, less than once per day for fruits) between educational levels. The low-education group had lower intakes of total FV, vegetables excluding Kimchi and fruit (both by frequency and quantity), but higher intakes of Kimchi, in both sexes in most years in which surveys were conducted. This group also had a higher proportion of adults with insufficient total FV and fruit intakes. The inequality, as indicated by the RII, was apparent in both sexes and in each survey year. The inequality in insufficient total FV intake increased between 1998 and 2009 in both sexes (P<0.05). An increase in the inequality in fruit intake was only detected in women (P<0.0001 for frequency and P=0.0285 for quantity, from 2007 to 2009). There is a wide discrepancy in total FV and fruit consumption across education levels among Korean adults. This inequality has increased over time for total FV intake in both sexes and for fruit intake in women.


Individual differences in reading skill and language lateralisation: a cluster analysis.
Individual differences in reading and cerebral lateralisation were investigated in 200 college students who completed reading assessments and divided visual field word recognition tasks, and received a structural MRI scan. Prior studies on this data set indicated that little variance in brain-behaviour correlations could be attributed to the effects of sex and handedness variables (Chiarello, Welcome, Halderman, & Leonard, 2009; Chiarello, Welcome, Halderman, Towler, et al., 2009; Welcome et al., 2009). Here a more bottom-up approach to behavioural classification (cluster analysis) was used to explore individual differences that need not depend on a priori decisions about relevant subgroups. The cluster solution identified four subgroups of college age readers with differing reading skill and visual field lateralisation profiles. These findings generalised to measures that were not included in the cluster analysis. Poorer reading skill was associated with somewhat reduced VF asymmetry, while average readers demonstrated exaggerated RVF/left hemisphere advantages. Skilled readers had either reduced asymmetries, or asymmetries that varied by task. The clusters did not differ by sex or handedness, suggesting that there are identifiable sources of variance among individuals that are not captured by these standard participant variables. All clusters had typical leftward asymmetry of the planum temporale. However, the size of areas in the posterior corpus callosum distinguished the two subgroups with high reading skill. A total of 17 participants, identified as multivariate outliers, had unusual behavioural profiles and differed from the remainder of the sample in not having significant leftward asymmetry of the planum temporale. A less buffered type of neurodevelopment that is more open to the effects of random genetic and environmental influences may characterise such individuals.


Functional reinnervation of rat hippocampus by locus coeruleus implants.
Transplants of the embryonic locus coeruleus (LC) region were implanted into the circuity of the hippocampal formation in adult rats in which the normal adrenergic afferents to the hippocampus had been removed. The growth of new adrenergic axons from the implant in the denervated hippocampus was followed for 1-14 months after surgery by means of fluorescence histochemistry, and the function of the implant-hippocampal connections was tested electrophysiologically after 2-3 months survival. In the successful cases the entire hippocampal formation was reinnervated from the LC implant within 3-6 months after operation, and the newly formed innervation still persisted unchanged by 14 months. The reinnervation was equally effective irrespective of the route by which the axons entered the hippocampus, i.e. along the lesioned fornix-fimbria or along a retrosplenial route. The pattern formed by the ingrowing LC axons mimicked to a large extent that of the normal LC afferents. Little growth was seen into denervated terminal fields of the commissural, septal or entorhinal afferents, pointing to a preference of the ingrowing LC fibers for the areas normally innervated by adrenergic afferents. In the electrophysiological experiments, stimulation of the LC implants caused (in 20 out of 29 cells monitored) an inhibition of the spontaneous activity of neurons in the host hippocampus. This inhibition had a relatively long latency and a long duration, similar to that observed after stimulation of the innate LC in the intact rat. As in the normal rat, the inhibitory responses were blocked by systemic or local application of the beta-adrenergic receptor blockers propranolol or sotalol. It is concluded that the adult rat brain is capable of carrying out all steps involved in correct functional reinnervation of a denervated region. Moreover, the implant-hippocampal preparation should be a highly suitable model system for functional studies of a central noradrenergic connection.


Preparation and characterization of zinc and copper co-doped WO3 nanoparticles: Application in photocatalysis and photobiology.
In this study, pure, Zn, Cu, Zn,Cu co-doped WO3 nanoparticles samples were prepared by precipitation and co-precipitation methods. These nanoparticles were characterized by field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), energy dispersive X-ray spectrometer (EDX), Dynamic light scattering (DLS), UV-visible and photoluminescence (PL) spectroscopy. The synthesized pure, Zn, Cu, Zn,Cu co-doped WO3 nanoparticles have smart optical properties and average sizes with 3.2, 3.12, 3.08 and 2.97eV of band-gap, 18.1, 23.2, 25.7 and 30.2nm, respectively. Photocatalytic activity of four nanoparticles was studying towards degradation of gentamicin antibiotic under ultraviolet and visible light irradiation. The result showed that Zn,Cu co-doped WO3 possessed high photocatalytic activity. The photocatalytic activity of WO3 nanoparticles could be remarkably increased by doping the Zn and Cu impurity. This can be attributed to the fact that the red shift of absorption edge and the trapping effect of the mono and co-doped WO3 nanoparticles. The research result presents a general and effective way to prepare different photocatalysts with enhanced visible and UV light-driven photocatalytic performance. Antibacterial activity of four different WO3 nanoparticles against Escherichia coli bacterium has been assessed by the agar disc method under light irradiation and dark medium. It is concluded from the present findings that WO3 nanoparticles can be used as an efficient antibacterial agent.


PTIO as a redox mediator to enhance organic contaminants oxidation by permanganate.
Although permanganate (Mn(VII)) is extensively utilized as a strong oxidizer for the purification of water, the direct reaction rates between some refractory pollutants and Mn(VII) are moderate or relatively low. In this study, we found that 2-phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl (PTIO), could act as a redox mediator to enhance bisphenol A (BPA) degradation by Mn(VII) at pH 5.0 - 9.0, with a removal higher than 80% over 5 min. Moreover, the Mn(VII)/PTIO system is highly efficient toward a broad spectrum of contaminants. Mechanism was elucidated as following: PTIO was oxidized by Mn(VII) to PTIO+, an oxoammonium cation. As a newly generated reactive species, PTIO+ could oxidize organics and be reduced to PTIOH (PTIO hydroxylamine) or PTIO simultaneously. The redox cycle of PTIO in consecutive runs as an electron shuttle proved its stability and reusability in Mn(VII) oxidation. In addition to being an electron shuttle, PTIO also acts as an activator of Mn(VII) to promote the production of MnO2, which plays a vital role in enhancing BPA abatement at the acidic condition. For the purpose of further understanding the interaction between PTIO and target contaminants, three corresponding degradation pathways for BPA were proposed. Notably, the transformation products of BPA coupling with PTIO were detected, indicating PTIO inhibited the self-coupling of BPA and facilitated the ring-opening pathway. In addition, the ubiquitous humic acid has a positive effect on the Mn(VII)/PTIO system, suggesting a high promise of this system for practical application.


The histone chaperone function of Daxx is dispensable for embryonic development.
Daxx functions as a histone chaperone for the histone H3 variant, H3.3, and is essential for embryonic development. Daxx interacts with Atrx to form a protein complex that deposits H3.3 into heterochromatic regions of the genome, including centromeres, telomeres, and repeat loci. To advance our understanding of histone chaperone activity in vivo, we developed two Daxx mutant alleles in the mouse germline, which abolish the interactions between Daxx and Atrx (DaxxY130A), and Daxx and H3.3 (DaxxS226A). We found that the interaction between Daxx and Atrx is dispensable for viability; mice are born at the expected Mendelian ratio and are fertile. The loss of Daxx-Atrx interaction, however, does cause dysregulated expression of endogenous retroviruses. In contrast, the interaction between Daxx and H3.3, while not required for embryonic development, is essential for postnatal viability. Transcriptome analysis of embryonic tissues demonstrates that this interaction is important for silencing endogenous retroviruses and for maintaining proper immune cell composition. Overall, these results clearly demonstrate that Daxx has both Atrx-dependent and independent functions in vivo, advancing our understanding of this epigenetic regulatory complex.


Long-Term Effect of Mechanical Thrombectomy in Stroke Patients According to Advanced Imaging Characteristics.
Data on long-term effect of mechanical thrombectomy (MT) in patients with large ischemic cores (≥ 70 ml) are scarce. Our study aimed to assess the long-term outcomes in MT-patients according to baseline advanced imaging parameters. We performed a single-centre retrospective cohort study of stroke patients receiving MT between January 1, 2010 and December 31, 2018. We assessed baseline imaging to determine core and mismatch volumes and hypoperfusion intensity ratio (with low ratio reflecting good collateral status) using RAPID automated post-processing software. Main outcomes were cross-sectional long-term mortality, functional outcome and quality of life by May 2020. Analysis were stratified by the final reperfusion status. In total 519 patients were included of whom 288 (55.5%) have deceased at follow-up (median follow-up time 28 months, interquartile range 1-55). Successful reperfusion was associated with lower long-term mortality in patients with ischemic core volumes ≥ 70 ml (adjusted hazard ratio (aHR) 0.20; 95% confidence interval (95% CI) 0.10-0.44) and ≥ 100 ml (aHR 0.26; 95% CI 0.08-0.87). The effect of successful reperfusion on long-term mortality was significant only in the presence of relevant mismatch (aHR 0.17; 95% CI 0.01-0.44). Increasing reperfusion grade was associated with a higher rate of favorable outcomes (mRS 0-3) also in patients with ischemic core volume ≥ 70 ml (aOR 3.58, 95% CI 1.64-7.83). Our study demonstrated a sustainable benefit of better reperfusion status in patients with large ischemic core volumes. Our results suggest that patient deselection based on large ischemic cores alone is not advisable.


["Kroly Than" Pharmacy, Sopron, Hungary].
The hundred year-long history of the "Károly Than" Pharmacy is surveyed. The widespread and versatile professional, humanitarian and public life activities from the turn of the century to the nationalisation and than to the privatisation are described. The paper also commemorates Professor Károly Nikolics, the prominent director and scientist, who has outstanding merits in making the city of Sopron one of the major headquarters of Hungarian pharmacy.


The kinky propulsion of Spiroplasma.
Bacteria have evolved many different means of generating movement. In this issue of Cell, Shaevitz et al. (2005) describe the swimming movement of a helical bacterium called Spiroplasma. They discover that Spiroplasma propels itself by generating two temporally distinct kinks that travel the length of the bacterium. These results point to the existence of a contractile apparatus that drives cell movement.


Bright white light does not improve narcoleptic symptoms.
Bright white light (500lx) for 4 h/day was applied to seven narcoleptic patients (age 47-65 years, mean 55 years). The effects of the light on the disturbed sleep-wake cycle in narcoleptics were investigated by the measurement of the following parameters: (1) excessive daytime sleepiness and sustained attention (multiple sleep latency test); (2) rest-activity cycles; (3) self-ratings (mood, anxiety, tiredness); (4) urinary cycles of 6-OH melatonin sulphate and cortisol; (5) sleep EEG. Treatment with bright light showed neither objective nor subjective changes in the clinical symptoms of narcolepsy. While similar "dosage" light applications can phase shift human circadian rhythms and improve depression and hypersomnia in winter depression, it is not an appropriate treatment for narcolepsy.


Renal Denervation: History and Current Status.
This review examines the early roots of renal denervation from its conceptualization and the creation of a percutaneous catheter system from a start-up company. As excitement began to grow with early animal experiments and human trials, renal denervation began to focus on the treatment of hypertension, culminating in a disappointing pivotal trial. Lessons learned from this trial are pushed forward, and renal denervation begins to gain clinical momentum as a new set of successful clinical trials emerge. The future for renal denervation eventually may extend beyond hypertension.


Changes in Aqueous Humor Lutein Levels of Patients with Cataracts after a 6-Week Course of Lutein-Containing Antioxidant Supplementation.
Oxidative damage is known to be an important cause of age-related cataracts and it has been suggested that administration of antioxidants, such as lutein, may delay the onset and progression of cataracts. Our previous investigation of human aqueous humor after the intake of a lutein-containing supplement demonstrated decreases in peroxidative products. This study evaluated the transportation of lutein into aqueous humor which is an important factor when measuring the antioxidant effects of lutein on the lens. This study enrolled 155 patients with binocular cataracts of the same grade. Serum and aqueous humor samples were collected during cataract surgery before (as pre-intake samples) and after 6 weeks of oral intake of Ocuvite + Lutein® (as post-intake samples). Lutein levels were measured with high-performance liquid chromatography. Lutein levels in both the serum and aqueous humor were significantly higher in the post-intake than the pre-intake samples. There were significant increases in the lutein levels in patients with lower pre-intake lutein serum levels. There was also a tendency for greater increases in patients with lower pre-intake aqueous humor lutein levels. These results demonstrate that oral lutein supplementation increases lutein levels, which further induce decreases in peroxidation in the aqueous humor. Furthermore, lutein supplementation may be more effective in patients with lower serum lutein levels.


Analysis of anthraquinones in rhubarb (Rheum palmatum and Rheum officinale) by supercritical fluid chromatography.
The first report on the separation of five anthraquinones (chrysophanol, physcion, emodin, aloeemodin, and rhein) from rhubarb by supercritical fluid chromatography indicates that this technique is an interesting analytical alternative not just for non-polar substances. Within less than five minutes the compounds could be baseline resolved, using a mobile phase comprising supercritical carbon dioxide and methanol with 0.05% diethylamine. The optimum stationary phase showed to be an Acquity UPC(2) HSS C18 SB 1.8 µm column, operated at a flow rate of 2 ml/min and a temperature of 30 °C. Method validation confirmed that the developed procedure is selective, linear (R(2)≥0.999), accurate (recovery rates: 95.4% to 103.1%), and precise (intra-day≤6.9%, inter-day≤4.7%); the limit of detection was below 0.5 ng on-column. The analysis of plant extracts was feasible with acceptable repeatability (σrel≤3.8%), and it determined 0.3 to 0.7% of free aglyca in the native samples. After hydrolysis according to the European Pharmacopoeia, a rise in the total content up to 2.1% was observed, with rhein being the most dominant derivative in nearly all specimens.


Prostate specific antigen decline after antiandrogen withdrawal: the flutamide withdrawal syndrome.
Post-therapy changes in prostate specific antigen (PSA) have been proposed as a surrogate end point for response in clinical trials of patients with hormone refractory prostatic cancer. While the specific criteria for response are evolving, there are concerns that changes in serum levels of PSA may be the result of changes in PSA expression or secretion independent of effects on cell growth and proliferation. We report 3 representative cases receiving complete androgen blockade with either gonadotropin-releasing hormone or orchiectomy plus the antiandrogen flutamide, which demonstrated sustained declines in serum PSA levels after discontinuation of the antiandrogen. Similar results have been observed in 6 additional patients. Whether this represents an agonist effect of the antiandrogen is unknown. The results suggest that a trial of flutamide withdrawal is justified in an asymptomatic patient with an increasing PSA before treatment with more toxic therapies. It also shows the importance of documenting sequential elevations in the marker before enrolling a patient in a clinical trial, and that changes in PSA must be interpreted cautiously in clinical trials when an antiandrogen is discontinued.


Human pulmonary artery endothelial cells in the model of mucopolysaccharidosis VI present a prohypertensive phenotype.
Mucopolysaccharidosis type VI (MPS VI) is an autosomal recessive lysosomal disorder caused by a deficient activity of N-acetylgalactosamine-4-sulfatase (ARSB). Pulmonary hypertension (PH) occurs in MPS VI patients and is a marker of bad prognosis. Malfunction of endothelium, which regulates vascular tonus and stimulates angiogenesis, can contribute to the occurrence of PH in MPS VI. The aim of the study was to establish a human MPS VI cellular model of pulmonary artery endothelial cells (HPAECs) and evaluate how it affects factors that may trigger PH such as proliferation, apoptosis, expression of endothelial nitric oxide synthase (eNOS), natriuretic peptide type C (NPPC), and vascular endothelial growth factor A (VEGFA). Increasing concentrations of dermatan sulfate (DS) reduce the viability of the cells in both ARSB deficiency and controls, but hardly influence apoptosis. The expression of eNOS in HPAECs is reduced up to two thirds in the presence of DS. NPPC shows a biphasic expression reaction with an increase at 50 μg/mL DS and reduction at 0 and 100 μg/mL DS. The expression of VEGFA decreases with increasing DS concentrations and absence of elastin, and increases with increasing DS in the presence of elastin. Our data suggest that MPS VI endothelium presents a prohypertensive phenotype due to the reduction of endothelium's proliferation ability and expression of vasorelaxing factors.