Pseudocarcinomatous Squamous Hyperplasia After Surgical Management Of Pediatric Ameloblastoma: An Immunohistochemical Study.
Pseudocarcinomatous squamous hyperplasia (PSH) affecting the jaws is uncommon. The mandible is the most common location, usually as a complication associated with osteomyelitis, medication-related osteonecrosis or osteoradionecrosis. Herein, we report an 8-year-old male patient presenting a solid ameloblastoma, plexiform type, who was treated by segmental mandibulectomy with bone grafting. Three months later, on the underlying graft, a sinus tract was observed, and a small bone fragment was resected which was diagnosed as bone sequestration associated with PSH. After 7-year follow-up, the patient is well, without alterations. To our knowledge, for the first time, we report in detail the immunohistochemical features of PSH which, in addition to epithelial component profile and chronic inflammatory cells, revealed a diffuse infiltration by dendritic cells, suggesting that epithelial cell-immune cell interactions in PSH pathogenesis should also be considered.


PCB 77 dechlorination products modulate pro-inflammatory events in vascular endothelial cells.
Persistent organic pollutants such as polychlorinated biphenyls (PCBs) are associated with detrimental health outcomes including cardiovascular diseases. Remediation of these compounds is a critical component of environmental policy. Although remediation efforts aim to completely remove toxicants, little is known about the effects of potential remediation byproducts. We previously published that Fe/Pd nanoparticles effectively dechlorinate PCB 77 to biphenyl, thus eliminating PCB-induced endothelial dysfunction using primary vascular endothelial cells. Herein, we analyzed the toxic effects of PCB congener mixtures (representative mixtures of commercial PCBs based on previous dechlorination data) produced at multiple time points during the dechlorination of PCB 77 to biphenyl. Compared with pure PCB 77, exposing endothelial cells to lower chlorinated PCB byproducts led to improved cellular viability, decreased superoxide production, and decreased nuclear factor kappa B activation based on duration of remediation. Presence of the parent compound, PCB 77, led to significant increases in mRNA and protein inflammatory marker expression. These data implicate that PCB dechlorination reduces biological toxicity to vascular endothelial cells.


The Swedish Demand-Control-Support Questionnaire (DCSQ): factor structure, item analyses, and internal consistency in a large population.
This paper examined the psychometric properties of the Swedish Demand-Control-Support Questionnaire (DCSQ), which is a shorter and modified version of Karasek's Job Content Questionnaire (JCQ). The study encompassed 5,227 workers born in 1953-57 from the population-based Hordaland Health Study. DCSQ, a 17-item questionnaire, covers psychological demands, decision latitude, and social support in the workplace. The workers were manually classified according to the Standard Classification of Occupations. The main statistical methods were principal component analyses, and estimation of internal consistency and the subscales' shared variance by Cronbach's coefficient a and Pearson's correlation coefficients, respectively. The study gave support to the tri-dimensional factor structure of DCSQ. Decision latitude tended to split into skill discretion and decision authority in skill-level homogeneous samples. The specificity of the item loadings was satisfactory except for "conflicting demands". The inter-correlation of the three main subscales was weak. The internal consistency of the subscales was generally satisfactory. The psychometric properties of DCSQ are satisfactory. Being shorter and easier to use than the more comprehensive JCQ, DCSQ represents an important alternative, particularly if respondent burden and data-collection costs need to be minimized.


Incidence of bone metastasis and factors contributing to its development and prognosis in newly diagnosed renal cell carcinoma: a population-based study.
The purpose of this study was to assess the incidence of and the risk factors and prognostic factors for bone metastasis (BM) in initial metastatic renal cell carcinoma (RCC) based on a large population analysis. Data were obtained for a total of 45,824 RCC patients recorded in the database of the Surveillance, Epidemiology, and End Results program of the National Cancer Institute between 2010 and 2014. Multivariate logistic and Cox regression analyses were used to identify the risk factors and prognostic factors associated with BM in RCC patients. Kaplan-Meier analysis was used to estimate the overall survival of RCC patients, and the difference between the survival curves was tested by log-rank tests. A total of 1,509 (3.29%) patients were diagnosed with bone metastases at initial diagnosis. Male gender, higher T stage, lymph node involvement, poor tumor grade, presence of lung, liver, and brain metastases, and the collecting duct type of RCC were positively associated with BM occurrence. The median survival time for RCC patients with bone metastases was 12.0 (95% confidence interval [CI]: 10.69-13.31) months, and the survival time for those with collecting duct, clear-cell, papillary, and chromophobe subtypes of RCC were 3 (95% CI: 0.23-5.77), 13 (95% CI: 11.60-14.40), 8 (95% CI: 5.09-10.91), and 11 (95% CI: 5.02-16.98) months; these differences were significantly different (P<0.01). Older age, higher T stage, lymph node involvement, poor tumor grade, the presence of lung, liver, and brain metastases, collecting duct RCC, and the absence of surgical treatments were the factors associated with worse prognoses. BM was highly prevalent and significantly decreased the survival rate of RCC patients. A number of factors associated with the development and prognosis of BM were identified, and these insights provide preventive guidelines for screening and treatment of BM in RCC patients.


[Department of epidemiology of the National Institute of Hygiene in Warsaw in the years 1951-2011--origins of forming, developmental ways in 60 years of work].
The paper discussed the origins of forming in 1951 the Department of Epidemiology, National Institute of Hygiene in Poland and its subsequent tasks. Relating to the evolving tasks, changes in the organizational structure, professional profile of the staff, main professional challenges and scientific achievements are described in 10 years cycles. Successive chapters address: scientific careers of the Department staff and contribution to scientific development of the whole institute among others; teaching and training, mainly targeted at the epidemiological service staff in Poland; editorial and publishing activities.


Improved detection of adenocarcinoma of serous fluids with p53 immunocytochemistry.
To investigate the potential value of p53 protein immunostaining in identifying malignant cells in serous fluids. We applied p53 immunostaining to 26 cytologically malignant, 8 suspicious and 34 benign specimens of serous fluids from 68 patients. For comparison, staining for carcinoembryonic antigen (CEA) was also done on all the specimens. CEA was positive in 23 of 26 (88%) cytomorphologically malignant, 3 of 8 (38%) suspicious and 1 of 34 benign cases. p53 Nuclear immunostaining was positive in 12/26 (46%) malignant, 2/8 (26%) suspicious and no benign cases. Correlation between p53 staining and serous fluid type (benign, suspicious or malignant) was significant. The P based on Fisher's exact test was < .0001. Two cases that were reported cytomorphologically as suspicious stained positively with p53; further investigation in those cases confirmed the diagnosis of metastatic adenocarcinoma. p53 Immunostaining of serous fluids seems to be of value in identifying carcinoma cells, especially in those cases that show inconclusive or bland cytologic features. Combining p53 with CEA immunostains in clinically or cytologically suspicious cases may assist in recognition of carcinoma cells and in pursuing an appropriate therapeutic approach.


[The effect of polypeptides from the thymus, bone marrow and bursa of Fabricius on the immunogenesis and hemostasis in neonatally thymectomized and antenatally bursectomized chickens].
The effect of polypeptides from the thymus, bone marrow and bursa of Fabricius on immunogenesis and hemostasis was investigated in neonatally thymectomized and antenatally bursectomized chickens. It has been established that polypeptide factors from the bursa of Fabricius have the most pronounced effect on the immunity and hemostasis.


Optimization of struvite crystallization protocol for pretreating the swine wastewater and its impact on subsequent anaerobic biodegradation of pollutants.
Higher contents of NH(4)(+) and SS in wastewater hamper the anaerobic digestion; necessitating its pretreatment to reduce them. This study reveals optimization of struvite/MAP precipitation protocol followed by anaerobic digestion of pretreated swine wastewater for pollutants removal. Levels of different treatments: stirring speeds, 400 and 160 rpm; pH values, 9.0, 9.5, 10.0, 10.5, 11.0 and 11.5; and P:Mg:N ratios, 1:1:1.2, 1:1:1.7, 1:1:2.2, 1:1:2.7, 1:1:4.0 and 1:1:5.0 were evaluated for MAP crystallization. Among various combinations, protocol comprising of initial 10 min stirring at 400 rpm followed by 160 rpm for 30 min, pH 10.0, and P:Mg:N ratio 1:1:1.2 rendered the best removal efficiency for NH(4)(+), PO(4)(3-), COD, TC and TOC. Subsequent anaerobic biodegradation revealed superiority of MAP supernatant over raw swine wastewater for methane yield and NH(4)(+)-N, PO(4)(3-)-P, COD, TC and TOC removals. It suggests that struvite precipitation as pretreatment to anaerobic digestion is highly effective and advantageous in wastewater treatment.


[Clinical structure of institutionalization in schizophrenic patients (rehabilitation aspect)].
The results of the studies of hospitalism formation in 173 patients with continuous-progressive schizophrenia which have been treated in the mental hospital for the period of 10-35 years, are presented. Six clinical variants of hospitalism depending upon unfavourably influencing factors of long-term isolation, inadequate medical therapy and hyperguardianship are distinguished: aspontaneous, apatho-abulic, asthenic, variant of hyperguardianship and overcautiousness, variant of a negative attitude towards a discharge, mixed. The depiction of the clinical variants of hospitalism at the remote stages of schizophrenia permits to use more differentially and effectively prophylactic measures and rehabilitative programs in relation to the patient's long-term hospitalizations.


Incorporation of labeled 2,4,5,2',4',5'-hexachlorobiphenyl into the nuclear fraction of rat hepatocytes in vivo.
2,4,5,2',4',5'-[14C] Hexachlorobiphenyl (2,4,5-HCB) a slowly metabolized PCB was given to rats by gastric incubation. The hepatocyte nuclei (HCN) were then isolated and treated with specific hydrolytic enzymes in order to separate the nucleic macromolecules, protein RNA and DNA. The results show that 2,4,5-HCB binds in vivo to hepatocyte nuclei. Liver nuclear proteins bind 70% of 2,4,5-HCB and 30% is found in the DNA fraction. No radioactivity was found in the nuclear RNA fraction at this experimental time (16 h).


Early prediction of major depression in chronic hepatitis C patients during peg-interferon alpha-2b treatment by assessment of vegetative-depressive symptoms after four weeks.
To study the predictive value of the vegetative-depressive symptoms of the Zung Depression Rating Scale for the occurrence of depression during treatment with peg-interferon alpha-2b of chronic hepatitis C (CHC) patients. The predictive value of vegetative-depressive symptoms at 4 wk of treatment for the occurrence of a subsequent diagnosis of major depressive disorder (MDD) was studied in CHC patients infected after substance use in a prospective, multi-center treatment trial in Belgium. The presence of vegetative-depressive symptoms was assessed using the Zung Scale before and 4 wk after the start of antiviral treatment. Out of 49 eligible patients, 19 (39%) developed MDD. The area under the ROC curve of the vegetative Zung subscale was 0.73, P = 0.004. The sensitivity at a cut-point of > 15/35 was 95% (95% CI: 74-100). The positive predictive value equalled 44% (95% CI: 29-60). In this group of Belgian CHC patients infected after substance use, antiviral treatment caused a considerable risk of depression. Seven vegetative-depressive symptoms of the Zung scale at wk 4 of treatment predicted 95% of all emerging depressions, at a price of 56% false positive test results.


Site-specific gene modification by oligodeoxynucleotides in mouse bone marrow-derived mesenchymal stem cells.
Synthetic oligodeoxynucleotides (ODNs) had been employed in gene modification and represent an alternative approach to 'cure' genetic disorders caused by mutations. To test the ability of ODN-mediated gene repair in bone marrow-derived mesenchymal stem cells (MSCs), we established MSCs cell lines with stably integrated mutant neomycin resistance and enhanced green fluorescent protein reporter genes. The established cultures showed morphologically homogenous population with phenotypic and functional features of mesenchymal progenitors. Transfection with gene-specific ODNs successfully repaired targeted cells resulting in the expression of functional proteins at relatively high frequency approaching 0.2%. Direct DNA sequencing confirmed that phenotype change resulted from the designated nucleotide correction at the target site. The position of the mismatch-forming nucleotide was shown to be important structural feature for ODN repair activity. The genetically corrected MSCs were healthy and maintained an undifferentiated state. Furthermore, the genetically modified MSCs were able to engraft into many tissues of unconditioned transgenic mice making them an attractive therapeutic tool in a wide range of clinical applications.


Acute subconjunctival pigmentation with an underlying ciliary body mass: An unusual case presentation.
Intraocular melanocytoma is a rare slowly growing benign tumor that may occur anywhere along the uveal tract including the ciliary body but is more commonly found near the optic disc. It is darkly pigmented and may exhibit fast growth and possibly malignant transformation. Ciliary body (CB) melanocytoma is rare and often misdiagnosed as a melanoma. We are reporting a case of CB melanocytoma in a 74-year old lady with unusual initial presentation of an acute onset of subconjunctival pigmentation and extra-scleral extension of the melanocytoma with coarse melanin granules. The diagnosis of melanocytoma was confirmed by histopathological examination of the prolapsed tissue and by ultrastructural studies. Literature review of similar cases is also summarized.


Remodeling of liver phospholipidomic profile in streptozotocin-induced diabetic rats.
Lipid homeostasis in liver is known to be altered with diabetes mellitus, ultimately leading to liver damage and related complications. The present work aimed to evaluate changes in the liver phospholipid profile after 4 months of uncontrolled hyperglycemia. Twenty Wistar rats were divided into two groups: control and streptozotocin-treated (T1DM). After 4 months, animals were sacrificed and morphological characterization of liver was performed and related with serum markers of hepatic damage. Lipid extracts were obtained from liver and phospholipid (PL) classes were quantified. Lipid molecular species were determined by LC-MS and LC-MS/MS, and fatty acids by GC-MS. Concomitantly with signs of hepatic damage we found variations in the relative amount of phospholipid classes in T1DM, characterized by a decrease in PLs with choline head group, and by an increase in the relative content of other PL classes. A remodeling in PL fatty acyl chains was observed in T1DM liver, with a similar pattern to all the PL classes, and consisting in the reduction of 16:0 and an increase of 18:0 and 18:2 acyl chains. The observed changes in T1DM lipid profile may contribute to the altered membrane properties underlying hepatic damage, worsening the metabolic alterations that characterize T1DM.


Residential greenness and dyslipidemia risk: Dose-response relations and mediation through BMI and air pollution.
Evidence on associations of residential greenness with dyslipidemia is limited, particularly regarding dose-response relations and mediation. To investigate associations between greenness and dyslipidemia, non-linear dose-response relationships and mediators. This cross-sectional study draws on the 2018 Fujian Behavior and Disease Surveillance (FBDS) cohort that used multi-stage stratified random sampling from the general population of Fujian Province, China. Participants with one or more abnormities in total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C) were classified as having dyslipidemia. Residential greenness was operationalized as 3-year average of the normalized difference vegetation index (NDVI500m) and enhanced vegetation index (EVI500m). A doubly robust approach was used for effect quantification. Dose-response relations were studied with natural cubic splines. Mediation via physical activity (PA), body mass index (BMI), PM2.5, PM10, SO2, and NO2 was also examined. Data from 43,183 participants were analyzed. Increases in NDVI500m and EVI500m residential greenness were associated with decreased dyslipidemia risk and improved blood lipids. Non-linear dose response relationships were discovered. Significant reduction of dyslipidemia risk was observed at levels of EVI500m > 0.48 and NDVI500m > 0.65. Joint mediation effects of PA, BMI, PM2.5, PM10, NO2, and SO2 on the associations of NDVI500m and EVI500m with dyslipidemia risk were 49.74% and 44.64%, respectively. Increased residential exposure to greenness was associated with decreased risk of dyslipidemia. A non-linear dose-response relationship between greenness and dyslipidemia suggests that specific thresholds of greenness need to be reached in order to achieve effects. BMI, PM2.5, and PM10 partially mediated the association.


High dose chemotherapy and autologous stem cell transplantation in nodular lymphocyte-predominant Hodgkin lymphoma: A retrospective study by the European society for blood and marrow transplantation-lymphoma working party.
Whilst autologous stem cell transplantation (auto-SCT) is considered standard of care for relapsed/refractory classical Hodgkin lymphoma, the role of auto-SCT in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is not well defined due to limited data. We report the first study on auto-SCT for NLPHL with a larger cohort. Eligible for this retrospective registry study were patients reported to the EBMT between 2003 and 2013, aged 18 or older with relapsed/refractory NLPHL who underwent first auto-SCT with disease chemosensitive to salvage therapy. NLPHL transformed to diffuse large B cell lymphoma were excluded. Sixty patients (83% male; median age 40 years) met the eligibility criteria. The median time between diagnosis and transplant was 21 months (IQR 13-58), and the median number of prior treatment lines was 2 (range 1-5), including rituximab in 63% of the patients. At auto-SCT, 62% of the patients were in complete remission (CR) and 38% in partial remission. Seventy-two percent of the patients received BEAM as high-dose therapy. With a median follow-up of 56 months (range 3-105), 5-year progression-free and overall survival (OS) were 66% and 87%, respectively. Univariate comparisons considering age, time from diagnosis to transplant, prior chemotherapy lines, and prior rituximab use failed to identify significant predictors for any survival endpoint except for being in CR at the time of auto-SCT (vs PR, P = .049) for OS. Auto-SCT in patients with relapsed/refractory NLPHL who are sensitive to salvage therapy gives excellent disease control and long-term survival independent of the time interval between diagnosis and transplant.


Functional profile of the isolated uremic nephron: intrinsic adaptation of phosphate transport in the rabbit proximal tubule.
The maintenance of phosphate homeostasis in uremia appears to be governed both by parathyroid hormone (PTH) and by PTH-independent adaptations in renal tubular function. The relative contributions of these two mechanisms that control phosphate excretion by the diseased kidney have been difficult to define in intact animals. The present study was designed to examine the nature of the adaptation of phosphate handling by the proximal tubule of subtotally nephrectomized, uremic rabbits in vitro. Euparathyroid and hyperparathyroid uremic rabbits were studied. Tubular sensitivity to PTH was examined in vitro. The dose-response relationship between bath PTH concentration and inhibition of lumen-to-bath phosphate flux (Jp-lb) in isolated perfused proximal straight tubules (PSTs) revealed that PTH sensitivity was increased in the euparathyroid uremic rabbits and was decreased in hyperparathyroid uremic rabbits. The dose-response to dibutyryl cAMP was the same as normal in both uremic groups. These data strongly suggest the existence of a receptor-mediated adaptation in the effects of PTH on the uremic proximal tubule. In addition to an altered PTH-sensitivity the uremic PST also exhibited an alteration in the basal rate of phosphate transport studied in the presence of normal rabbit serum. Although net volume flux across the PST increased in both uremic groups as a possible consequence of hypertrophy, net phosphate flux per unit length was unchanged. Considering the increase of luminal area in these tubules, net phosphate flux per unit reabsorptive surface area was actually decreased. This dissociation is supportive of the existence of an intrinsic tubular adaptation which is independent of the size of the tubule per se. These studies indicate that there is an intrinsic adaptation of the basal rate of phosphate transport by the uremic rabbit proximal tubule and that the sensitivity of the tubule to PTH is altered. The data are strongly suggestive of an increase in the number of PTH receptors in the proximal tubule of the euparathyroid uremic rabbit and suggest that "down regulation" or persistent occupancy of these receptors occurs when hyperparathyroidism supervenes.


Multiple requirements for Hes 1 during early eye formation.
During embryogenesis, multiple developmental processes are integrated through their precise temporal regulation. Hes1 is a transcriptional repressor that regulates the timing of mammalian retinal neurogenesis. However, roles for Hes1 in early eye development have not been well defined. Here, we show that Hes1 is expressed in the forming lens, optic vesicle, cup, and pigmented epithelium and is necessary for proper growth, morphogenesis, and differentiation of these tissues. Because Hes1 is required throughout the eye, we investigated its interaction with Pax6. Hes1-Pax6 double mutant embryos are eyeless suggesting these genes are coordinately required for initial morphogenesis and outgrowth of the optic vesicle. In Hes1 mutants, Math5 expression is precocious along with retinal ganglion cell, amacrine, and horizontal neuron formation. In contrast to apparent cooperativity between Pax6 and Hes1 during morphogenesis, each gene regulates Math5 and RGC genesis independently. Together, these studies demonstrate that Hes1, like Pax6, simultaneously regulates multiple developmental processes during optic development.


Hydrodynamic control of droplet division in bifurcating microchannel and its application to particle synthesis.
We describe herein a microfluidic system for active and precise control of droplet division at a bifurcation point in a microchannel. Water-in-oil or oil-in-water droplets, which were initially formed at a T-junction, were introduced into the bifurcation point, and then divided into two daughter droplets. By continuously introducing 'tuning flow' into the downstream of one of the branch channels, and by controlling the flow rates distributed into the two branch channels, the sizes of the daughter droplets could be precisely tuned. The ratio of the volumetric flow rates into the branch channels was estimated by regarding the microchannel network as a resistive circuit. In addition, we performed synthesis of monodispersed polymer particles with controlled sizes utilizing the presented system. The ability to hydrodynamically control the droplet sizes will open new possibilities not only for producing useful emulsions, but also for conducting controlled chemical and biochemical reactions in a confined space.


Myosin-V opposes microtubule-based cargo transport and drives directional motility on cortical actin.
Intracellular transport is driven by motor proteins that either use microtubules or actin filaments as their tracks, but the interplay between these transport pathways is poorly understood. Whereas many microtubule-based motors are known to drive long-range transport, several actin-based motors have been proposed to function predominantly in cargo tethering. How these opposing activities are integrated on cargoes that contain both types of motors is unknown. Here we use inducible intracellular transport assays to show that acute recruitment of myosin-V to kinesin-propelled cargo reduces their motility near the cell periphery and enhances their localization at the actin-rich cell cortex. Myosin-V arrests rapid microtubule-based transport without the need for regulated auto- or other inhibition of kinesin motors. In addition, myosin-V, despite being an ineffective long-range transporter, can drive slow, medium-range (1-5 μm), point-to-point transport in cortical cell regions. Altogether, these data support a model in which myosin-V establishes local cortical delivery of kinesin-bound cargos through a combination of tethering and active transport.


Tissue-Specific Promoters in the CNS.
This chapter outlines some general principles of transcriptional targeting approaches using viral vectors in the central nervous system. Transcriptional targeting is first discussed in the context of vector tropism and appropriate delivery. Then, some of our own attempts to restrict expression of therapeutic factors to distinct brain cell populations are discussed, followed by a detailed description of the setscrews that are available for these experiments. A critical discussion of current stumbling blocks and necessary developments to achieve clinical applicability of advanced targeted vector systems is provided.


Solid state NMR studies and chemical shift calculations of a gold(I) complex with a diphosphacyclobutadiene cobaltate sandwich anion.
The (31)P and (13)C solid state nuclear magnetic resonance spectra of a neutral gold(I) complex with bis(diphosphacyclobutadiene) cobaltate anions, [Au{Co(P2C2tPent2)2}2(PMe3)2], are reported. Complete (31)P resonance assignments have been derived from saturation transfer, radio-frequency driven recoupling (RFDR) and RTOBSY experiments and confirmed further by ab-initio calculations of magnetic shielding tensors by density functional theory, with consideration of relativistic effects. Coordination of the diphosphacyclobutadiene ring with gold(I) results in a high-frequency shift of the (31)P signal of the directly coordinated P atom, whereas a low-frequency shift is observed for the P atom at the opposite end of that ring. Based on these results, a previous assignment made for the complex salts [Au(PMe3)4][Au{Co(P2C2Ad2)2}2] and [K(18-crown-6)(thf)2][Au{Co(P2C2Ad2)2}2] (Ad=adamantyl) must be corrected.


Self-apposing stent-assisted coil embolization for the treatment of coronary artery aneurysm.
Coronary artery aneurysms (CAA) represent an uncommon disease with yet unclear standards of treatment. Clinical and anatomic characteristics determine choice of treatment. Stent-assisted coil embolization has been described as a valuable option for management of patients with wide-neck coronary aneurysms. Choice of appropriate stent sizing can be challenging particularly when there is a large difference between proximal and distal diameters. We report a case of stent-assisted coil embolization of a coronary aneurysm using a self-expandable stent. This type of stent can be helpful to treat CAA involving coronary sites where marked tapering of vessel diameter is often present.


Subclinic effect of the administration of T-2 Toxin and Nivalenol in mice.
Four experiments using T-2 toxin and nivalenol at different dosage, which represented the 25% and 40% of the LD50 (experiment A: 1.04 mg of T-2 toxin per kilogram of body weight, experiment B: 2.34 mg of T-2 toxin/kg b.w., experiment C: 1.04 mg of T-2 toxin/kg b. w. and 2.34 mg of T-2 toxin/kg b.w.; experiment D: 0.82 mg of nivalenol/kg b.w. and 1.845 mg of nivalenol/kg b.w.) were conducted on 400 mice. Both toxins were administered to mice of different ages (experiments A and B were adults, experiment C and D were young) by intraperitoneal single injection, and the clinical signs, hematological variables and histoanatomo pathological changes were studied. All animals survived. No changes anatomo-histopathological nor significative differences in weight gain were observed. Different behaviors were found for nivalenol and T-2 toxin. The most significant change was the increase in the level of monocytes in old animals, so this could be a biological indicator for T-2 toxin subclinical intoxication.


The effects of polyamines on a residue-specific human plasma ribonuclease.
A ribonuclease, purified some 2700-fold from human plasma, exhibited a strong predilection for the hydrolysis of internucleotide bonds containing cytidylic acid. Analysis of [3'-32P]- and [5'-32P]phosphoryl-terminal fragments obtained after enzymic digestion of rabbit liver and yeast RNA indicated that the nucleotide found at the 3' terminus of the fragments was invariably cytidylic acid. The nucleotide at the 5' terminus varied between cytidylic and uridylic acids in a ratio of 9:1. When characterized by DEAE-cellulose chromatography, approximately 70 per cent of the digest consisted of oligonucleotides from 4 to 8 nucleotides in length. Enzyme activity, when measured in low ionic strength buffer, could be increased severalfold above control levels by the addition of either of the polyamines, spermidine or spermine. These substances also restored nucleolytic activity to preparations inhibited by such ordered synthetic polyribonucleotides as polyguanylic acid. Estimations of the molecular weight of the enzyme, both by Sephadex gel filtration and sucrose density centrifugation, indicate that the weight may vary, depending on the presence or absence of certain cations. Of the cations examined, spermidine and spermine appear to have the greatest effect, causing an alteration in molecular weight from greater than 150,000 to approximately 32,000.


Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe.
We have recently reported on a technique of gamma probe localization of radiolabelled lymph nodes to identify the sentinel node in malignant melanoma. In order to determine whether this technique is applicable to assist in staging breast cancer, a pilot study was begun to address two questions: (i) can the sentinel lymph node draining a breast cancer be identified for selective resection; and (ii) is the sentinel lymph node predictive of the status of the entire axillary lymph nodes? One to four hours prior to axillary lymph node dissection, 22 consecutive patients had approximately 0.4 mCi of technetium sulfur colloid in 0.5 ml saline injected around the perimeter of the breast lesion. A hand-held gamma counter was used at surgery to locate the lymph node(s) receiving drainage from the breast. A sentinel lymph node was identified in 18 of 22 patients. Of these 18 patients, the sentinel lymph node was positive in seven of seven patients, with pathologically verified metastatic breast cancer to at least one lymph node. In three out of seven patients, the sentinel lymph node was the only lymph node with metastatic cancer. In this pilot study of breast cancer patients, we conclude that: (i) radiolocalization and selective resection of sentinel lymph nodes is possible; and (ii) the sentinel lymph node appears to predict correctly the status of the remaining axilla. These data justify a larger clinical trial to verify the value of this technique.


What do we not know about mitochondrial potassium channels?
In this review, we summarize our knowledge about mitochondrial potassium channels, with a special focus on unanswered questions in this field. The following potassium channels have been well described in the inner mitochondrial membrane: ATP-regulated potassium channel, Ca(2+)-activated potassium channel, the voltage-gated Kv1.3 potassium channel, and the two-pore domain TASK-3 potassium channel. The primary functional roles of these channels include regulation of mitochondrial respiration and the alteration of membrane potential. Additionally, they modulate the mitochondrial matrix volume and the synthesis of reactive oxygen species by mitochondria. Mitochondrial potassium channels are believed to contribute to cytoprotection and cell death. In this paper, we discuss fundamental issues concerning mitochondrial potassium channels: their molecular identity, channel pharmacology and functional properties. Attention will be given to the current problems present in our understanding of the nature of mitochondrial potassium channels. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.


A fungal dioxygenase CcTet serves as a eukaryotic 6mA demethylase on duplex DNA.
N6-methyladenosine (6mA) is a DNA modification that has recently been found to play regulatory roles during mammalian early embryo development and mitochondrial transcription. We found that a dioxygenase CcTet from the fungus Coprinopsis cinerea is also a dsDNA 6mA demethylase. It oxidizes 6mA to the intermediate N6-hydroxymethyladenosine (6hmA) with robust activity of 6mA-containing duplex DNA (dsDNA) as well as isolated genomics DNA. Structural characterization revealed that CcTet utilizes three flexible loop regions and two key residues-D337 and G331-in the active pocket to preferentially recognize substrates on dsDNA. A CcTet D337F mutant protein retained the catalytic activity on 6mA but lost activity on 5-methylcytosine. Our findings uncovered a 6mA demethylase that works on dsDNA, suggesting potential 6mA demethylation in fungi and elucidating 6mA recognition and the catalytic mechanism of CcTet. The CcTet D337F mutant protein also provides a chemical biology tool for future functional manipulation of DNA 6mA in vivo.


Physico-Chemical Condition Optimization during Biosynthesis lead to development of Improved and Catalytically Efficient Gold Nano Particles.
Biosynthesis of nanoparticles has gained great attention in making the process cost-effective and eco-friendly, but there are limited reports which describe the interdependency of physical parameters for tailoring the dimension and geometry of nanoparticles during biological synthesis. In the present study, gold nanoparticles (GNPs) of various shapes and sizes were obtained by modulating different physical parameters using Trichoderma viride filtrate. The particles were characterized on the basis of visual observation, dynamic light scattering, UV-visible spectroscopy, transmission electron microscopy, fourier transform infrared spectroscopy, and X ray diffraction. While the size varied from 2-500 nm, the shapes obtained were nanospheres, nanotriangles, nanopentagons, nanohexagons, and nanosheets. Changing the parameters such as pH, temperature, time, substrate, and culture filtrate concentration influenced the size and geometry of nanoparticles. Catalytic activity of the biosynthesized GNP was evaluated by UV-visible spectroscopy and confirmed by gas chromatography-mass spectrometric analysis for the conversion of 4-nitrophenol into 4-aminophenol which was strongly influenced by their structure and dimension. Common practices for biodegradation are traditional, expensive, require large amount of raw material, and time taking. Controlling shapes and sizes of nanoparticles could revolutionize the process of biodegradation that can remove all the hurdles in current scenario.


Absence of seminal plasma from sperm-rich fraction decreases boar sperm quality characteristics during the course of liquid storage.
Seminal plasma (SP), the fluid that surrounds the sperm cells, is known to exert substantial influence on sperm physiology. The SP has a pivotal role in sperm function in vivo, and due to its components, it functions in an ambiguous manner in vitro, simultaneously possessing deleterious and beneficial effects. This experiment aimed to describe the differences between the presence or absence of SP from the sperm-rich fraction on some spermatozoa characteristics (kinetics, plasma and acrosome membrane integrity, lipid peroxidation and capacitation-like changes). Furthermore, this experiment focused on distinguishing the effects of SP on the variables evaluated from the effects of centrifugation during SP removal. Total and progressive sperm motility, as well as integrity of plasma and acrosome membranes, were less (P < 0.05) in the absence of SP. Membrane lipid peroxidation (P < 0.05) and sperm membrane stability (P < 0.05) did not differ among treatments. The SP from the sperm-rich fraction is important for the maintenance of adequate structural and functional characteristics of extended liquid boar semen and should be present in seminal doses throughout storage. Furthermore, the detrimental effect on the variables evaluated was caused solely by the absence of SP and not by the process of removal through centrifugation at 500 x g for 10 min.


STING agonist-containing microparticles improve seasonal influenza vaccine efficacy and durability in ferrets over standard adjuvant.
The current pandemic highlights the need for effective vaccines against respiratory viruses. An ideal vaccine should induce robust and long-lasting responses with high manufacturing scalability. We use an adjuvant comprised of a Stimulator of Interferon Genes (STING) agonist incorporated in a scalable microparticle platform to achieve durable protection against the influenza virus. This formulation overcomes the challenges presented by the cytosolic localization of STING and the hydrophilicity of its agonists. We evaluated a monoaxial formulation of polymeric acetalated dextran microparticles (MPs) to deliver the STING agonist cyclic GMP-AMP (cGAMP) which achieved >10× dose-sparing effects compared to other published work. Efficacy was evaluated in ferrets, a larger animal model of choice for influenza vaccines. cGAMP MPs with recombinant hemagglutinin reduced viral shedding and improved vaccine outcomes compared to a seasonal influenza vaccine. Importantly, sustained protection against a lethal influenza infection was detected a year after a single dose of the vaccine-adjuvant.


Kay's mitral valve repair for mitral regurgitation due to ruptured chordae tendineae--clinical and hemodynamic observations.
Kay's mitral valve repair was performed in six consecutive patients with symptomatic mitral regurgitation due to ruptured chordae tendineae of the posterior leaflet. All patients including one with mild residual murmur showed a marked decrease in the heart size and significant clinical improvement. Postoperative hemodynamic studies, performed in four patients, showed restoration of normal or near-normal dynamics. The medium-term follow-up, 15 to 30 months after the operation, revealed continuing asymptomatic states in all. The function of the repaired valves was significantly better than that of the Hancock mitral bioprostheses. The advantages of this procedure compared with mitral valve replacement for the same condition were stressed.


Cidec promotes the differentiation of human adipocytes by degradation of AMPKα through ubiquitin-proteasome pathway.
We previously showed that Cidec was localized on the surface of lipid droplets and could promote the differentiation of human adipocytes, but the molecular mechanism was still unknown. In this study, we first sought to identify proteins that interact with Cidec using yeast two-hybrid system. The results revealed that Cidec could directly interact with AMPKα1 subunit. We further showed that AMPKα levels decreased while Cidec increased during the adipogenic differentiation of human adipocytes. Meanwhile, we observed that the increased Cidec could reduce AMPKα level in adipocytes, and the downregulation of AMPKα could help to promote the differentiation of adipocytes. The results of co-immunoprecipitation and immunofluorescent proved that Cidec biochemically interacted and co-localized with AMPKα1, which meant Cidec was a regulator for AMPKα stability through an ubiquitin-proteasome pathway. Our data suggested that Cidec could interact with and down-regulate AMPKα through an ubiquitin-proteasome degradation pathway, which provided a possible mechanism of Cidec in promoting human adipocytes differentiation. Our work proposed a new possible mechanism for human adipogenesis, and also provided a potential role of AMPKα as a target in treating obesity or obesity-related diseases.


The concept of cone creation to treat isolated tricuspid valve dysplasia and the case of a double-orifice tricuspid valve.
Isolated tricuspid valve dysplasia is a rare disease characterized by a wide spectrum of possible anomalies. We describe the use of the Cone concept to treat a patient with a double-orifice tricuspid valve with massive regurgitation and severe deficit of coaptation. Three adult patients with congenital non-Ebstein tricuspid valve anomaly characterized by severe coaptation deficiency underwent tricuspid valve repair applying the Cone technique. In particular, we describe the case of a symptomatic 21-year-old woman with a double-orifice tricuspid valve, with massive regurgitation and severe right ventricular dilatation. The tricuspid valve was transformed from a double-orifice valve into a single-orifice valve. The most superior orifice was opened, and the tissue surrounding the orifice was used to extend the leaflet of the inferior orifice. A Cone was created, and a ring annuloplasty was used to stabilize the result. The patient was discharged home after 7 days with trivial residual tricuspid regurgitation and no significant antegrade gradient. The final coaptation height was 2.8 cm. The cardiothoracic ratio decreased from 0.77 to 0.59 after 2 months, and symptoms promptly improved. Over the past 2 years, we have applied the Cone creation concept to patients with a severely dysplastic tricuspid valve with excellent early results. One patient had a double-orifice tricuspid valve, and a Cone repair concept was adopted anyway. One orifice was sacrificed, and surrounding tissue was used to augment the leaflets of the other orifice. A Cone was created to improve central coaptation with a good initial result.


c-Kit-stem cell factor signal-independent development of interstitial cells of Cajal in murine small intestine.
c-Kit receptor tyrosine kinase and its ligand stem cell factor (SCF) play critical roles in regulating the development and proliferation of various cells, including the interstitial cells of Cajal (ICC) in the gastrointestinal tract. Many subtypes of ICC are known to be lacking in c-Kit-SCF-insufficient mice, such as W/Wv and Sl/Sld, whereas ICC-deep muscular plexus (DMP) in small intestine are not lacking. In this study, we examine ICC-DMP development in normal and c-Kit-SCF signal-insufficient mice. In normal mice, numerous ICC-DMP labeled with c-Kit and neurokinin 1 receptor (NK1R) antibodies were observed only in the duodenum on the day of birth, in the duodenum and the jejunum on postnatal day 4 and throughout the small intestine after postnatal day 6. In W mutant mice (W/Wv, Wv/Wv, W/W), ICC-DMP investigated using c-Kit and NK1R immunoreactivities were similar to that in normal mice. c-Kit ligand SCF-deficient mice (Sl/Sl) also showed almost identical ICC-DMP development and proliferation as normal mice. These results show that the development and proliferation of ICC-DMP occur in the postnatal period independent of c-Kit-SCF signaling.


Shared determinants of native and denatured bovine serum albumin are recognized by both B- and T-cells.
The antigenic relationship between native and denatured bovine serum albumin (BSA) was investigated by examining specificity of antibodies directed against both proteins. Polyclonal antibodies produced to native and denatured BSA in hyperimmunized mice were specific for the homologous molecule. In contrast, polyclonal antibodies formed early in the response to native BSA reacted both the denatured and the native molecule. Monoclonal antibodies to native BSA were specific for the homologous antigen, while one of three clones prepared by immunization with denatured BSA produced an antibody cross-reactive with native BSA. Our results suggest that shared determinants of native and denatured BSA molecules can be recognized by both B- and T-cells.


Structural changes produced in Kupffer cells in the rat liver by injection of lipopolysaccharide.
The fine structure of Kupffer cells has been studied at various times after an intravenous injection of lipopolysaccharide of Salmonella abortus equii. The most prominent effects were: an increase in the number and dimensions of phagocytic vacuoles (often containing ingested LPS and neutrophilic granulocytes); mitochondrial damage, including disintegration of the matrix and cristae; an increase in the amount of dilated, lucent rough endoplasmic reticulum; presence of fat droplets in the cytoplasm. Five days after injection of lipopolysaccharide, the Kupffer cells had resumed their normal ultrastructure. Several minutes after injection of lipopolysaccharide, platelets adhered to the Kupffer and endothelial cells. Between one and six hours, neutrophilic granulocytes accumulated in the liver sinusoids. The resulting obstruction of the hepatic microcirculation most probably affected cellular ultrastructure by ischaemia. At three days, the number of Kupffer cells was doubled, and increased further at later time intervals.


Species differences in sensitivity of nucleoside transport in erythrocytes and cultured cells to inhibition by nitrobenzylthioinosine, dipyridamole, dilazep and lidoflazine.
Differences in sensitivity of uridine transport in erythrocytes and cultured cells to inhibition by dipyridamole, dilazep and lidoflazine were largely species-specific; uridine transport in human cells, and probably in pig and rabbit cells, was 2-3- and 10-times more sensitive to inhibition by dipyridamole (IC50 approx. 50 nM) and about 10- and 20-times more sensitive to dilazep inhibition (IC50 approx. 5 nM) than transport in mouse and rat cells, respectively. Uridine transport in human erythrocytes and HeLa cells was strongly inhibited by lidoflazine (IC50 10-140 nM), whereas that in both mouse and rat cells was highly resistant (IC50 greater than 10 microM). Superimposed on species-specific differences were some cell type specific differences in sensitivity of nucleoside transport to these inhibitors. Uridine transport in Walker 256 rat carcinoma cells was more resistant to dipyridamole and dilazep than that of other rat cells. Transport in human Hep-2 cells was more resistant to lidoflazine (IC50 2000 nM) than that of human erythrocytes and HeLa cells, whereas it showed similar sensitivity to dilazep and dipyridamole. Uridine transport in Chinese hamster cells was also more resistant to dilazep than that of baby hamster kidney cells. In addition HeLa cells and clones thereof expressed uridine transporters (about 50% each) with difference of about 1000-fold in sensitivity to inhibition by dilazep (IC50 approx. 5 nM and 5 microM, respectively).


Silver nanoparticles modulate mitochondrial dynamics and biogenesis in HepG2 cells.
Silver nanoparticles (AgNPs) are inevitably released into the environment owing to their widespread applications in industry and medicine. The potential of their toxicity has aroused a great concern. Previous studies have shown that AgNPs exposure in HepG2 cells is primarily related to the damage of mitochondria, which includes induction of mitochondrial swelling and increase of intracellular levels of reactive oxygen species (ROS), the collapse of mitochondrial membrane potential and induction of apoptosis through a mitochondrial pathway. In this study, the effects of AgNPs exposure in HepG2 cells on mitochondrial dynamics and biogenesis were investigated. AgNPs were found to induce mitochondrial morphological and structural alterations. The expressions of key proteins (Drp1, Fis1, OPA1, Mff, Mfn1, and Mfn2) related to mitochondrial fission/fusion event were changed. Especially the expression of fission-related protein 1 (p-Drp1) (Ser616) was significantly up-regulated, whereas the expression of mitochondrial biogenesis protein (PGC-1α) was reduced in AgNP-treated cells. Concomitantly, the expression of autophagy marker proteins (LC3B and p62) was increased. The results suggested that AgNPs could trigger cytotoxicity by targeting the mitochondria, resulting in the disruption of mitochondrial function, damage to the mitochondrial structure and morphology, interfering in mitochondrial dynamics and biogenesis. The mitochondria could be a critical target of AgNPs in cells. The functions of mitochondria could be used for assessing the cytotoxic effects associated with AgNPs in cells.


MR imaging of the TMJ. MR diagnosis and intraoperative findings.
Magnetic resonance imaging provides the possibility of a non-invasive method for the investigation of the soft tissues of the temporomandibular joint (TMJ). Between March 1991 and August 1992 we performed static and dynamic magnetic resonance images (MRI) on 47 TMJs of 37 symptomatic patients using a MR-tomograph with a 6.5 cm surface coil. MR diagnosis could be verified in 15 joints at operation and in 3 cases by arthrotomography. Disc position was confirmed in 80%, perforations were missed in 2 out of 3 cases and two more perforations became obvious during operation. One patient refused MR examination, in 2 cases MRI had to be abandoned because of the patient's claustrophobia. In our work we wanted to show that MRI is a reliable tool to determine disc position, disc shape and disc behaviour during motion. Detection of perforations is still the domain of arthrography.


Dynamics of multiple nuclei in Ashbya gossypii hyphae depend on the control of cytoplasmic microtubules length by Bik1, Kip2, Kip3, and not on a capture/shrinkage mechanism.
Ashbya gossypii has a budding yeast-like genome but grows exclusively as multinucleated hyphae. In contrast to budding yeast where positioning of nuclei at the bud neck is a major function of cytoplasmic microtubules (cMTs), A. gossypii nuclei are constantly in motion and positioning is not an issue. To investigate the role of cMTs in nuclear oscillation and bypassing, we constructed mutants potentially affecting cMT lengths. Hyphae lacking the plus (+)end marker Bik1 or the kinesin Kip2 cannot polymerize long cMTs and lose wild-type nuclear movements. Interestingly, hyphae lacking the kinesin Kip3 display longer cMTs concomitant with increased nuclear oscillation and bypassing. Polymerization and depolymerization rates of cMTs are 3 times higher in A. gossypii than in budding yeast and cMT catastrophes are rare. Growing cMTs slide along the hyphal cortex and exert pulling forces on nuclei. Surprisingly, a capture/shrinkage mechanism seems to be absent in A. gossypii. cMTs reaching a hyphal tip do not shrink, and cMT +ends accumulate in hyphal tips. Thus, differences in cMT dynamics and length control between budding yeast and A. gossypii are key elements in the adaptation of the cMT cytoskeleton to much longer cells and much higher degrees of nuclear mobilities.


Climate of doubt: A re-evaluation of Büntgen and Di Cosmo's environmental hypothesis for the Mongol withdrawal from Hungary, 1242 CE.
In their recent article published in the journal Scientific Reports, Büntgen and Di Cosmo have attempted to solve the historical mystery of the sudden Mongol withdrawal from Hungary after a year-long occupation. We cannot share the authors' viewpoint that environmental circumstances contributed to the decision of the Mongols to abandon Hungary since the hypothesis lacks support from environmental, archaeological and historical evidence. Historical source material in particular suggests that the Mongols were able to settle and sustain their herds in Hungary as is clearly stated in a letter by King Bela IV to the pope. The Mongol army arrived in the kingdom at the end of a severe drought, and we present empirical evidence that the abundant rain in the spring of 1242 CE did not worsen but rather improved their prospects for sufficient food supplies and pasturage. The marshy terrain of the Hungarian Plain likely did not precipitate the Mongol withdrawal as the Mongol high command ultimately stationed their main forces around the marshy Volga Delta. In contrast to what Büntgen and Di Cosmo have suggested, we argue that the reasons for the sudden withdrawal cannot be explained largely by environmental factors.


"It used to be about the kids": nutrition reform and the Montreal Protestant School Board.
The nutrition programs that developed in Montreal Protestant schools during the 1970s attest to a deepening awareness of child and adolescent welfare. The combination of grassroots activism and government support that brought about these initiatives took place in the context of post-Quiet Revolution Quebec, when Montrealers were grappling with the role that the newly activist state should play in social life. At the same time, school nutrition reform was part of a broader ongoing renegotiation of state responsibility. Both in Canada and the United States, governments were steadily assuming a mantle of responsibility for expanded liberal rights.


TransOmic analysis of forebrain sections in Sp2 conditional knockout embryonic mice using IR-MALDESI imaging of lipids and LC-MS/MS label-free proteomics.
Quantitative methods for detection of biological molecules are needed more than ever before in the emerging age of "omics" and "big data." Here, we provide an integrated approach for systematic analysis of the "lipidome" in tissue. To test our approach in a biological context, we utilized brain tissue selectively deficient for the transcription factor Specificity Protein 2 (Sp2). Conditional deletion of Sp2 in the mouse cerebral cortex results in developmental deficiencies including disruption of lipid metabolism. Silver (Ag) cationization was implemented for infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) to enhance the ion abundances for olefinic lipids, as these have been linked to regulation by Sp2. Combining Ag-doped and conventional IR-MALDESI imaging, this approach was extended to IR-MALDESI imaging of embryonic mouse brains. Further, our imaging technique was combined with bottom-up shotgun proteomic LC-MS/MS analysis and western blot for comparing Sp2 conditional knockout (Sp2-cKO) and wild-type (WT) cortices of tissue sections. This provided an integrated omics dataset which revealed many specific changes to fundamental cellular processes and biosynthetic pathways. In particular, step-specific altered abundances of nucleotides, lipids, and associated proteins were observed in the cerebral cortices of Sp2-cKO embryos.


Improvements in Virologic Control Among PWH Over Time: Narrowing the Gap Between Those With and Without STIs.
Using the incidence of bacterial sexually transmitted infection (STI) as a surrogate for condomless sexual behavior, we assessed the association between STI and uncontrolled HIV replication among in-care persons with HIV (PWH) enrolled in a longitudinal HIV cohort study in the District of Columbia (the DC Cohort). Although STI occurrence initially correlated with higher HIV viral load (VL), this difference became more attenuated over time (2012-2016). This was true overall and among those with the greatest number of STIs [age 18-34, men who have sex with men (MSM)]. This likely reflects gains in population-wide virologic control through improved antiretroviral therapy and access to care, which helps mitigate the risk of HIV transmission.


Catecholamine-uptake inhibitors prevent the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mouse brain.
Male albino mice were injected subcutaneously with 50 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Seven days after administration, the striatal levels of dopamine(DA) and its metabolites were markedly reduced, as was the cortical level of noradrenaline (NA). Pretreatment with the selective inhibitor of DA uptake, GBR 13098, selectively and totally prevented the reduction of DA and its metabolites, whereas the selective inhibitor of NA uptake, maprotiline, selectively protected against NA depletion. The unselective inhibitors of DA and NA uptake, mazindol and nomifensine, prevented the MPTP-induced depletion of both DA and NA.


Effect of aqueous extracts of Ecballium elaterium rich, in the rabbit model of rhinosinusitis.
This study was designated to investigate anti-inflammatory effect of aqueous extract of Ecballium elaterium, which is topically applied for treatment of rhinosinusitis as a traditional folk medicine in Turkey. Therapeutic potential of E. elaterium as an anti-inflammatory agent was examined by measurement of NO* metabolites in a rabbit model of rhinosinusitis. The results showed that both activity of NOS enzyme and concentration of NO* metabolites were significantly reduced by topical administration of E. elaterium extract in therapy group as compared to the control. Thus, the data suggest E. elaterium extract may have the potential to be used as anti-inflammation agent, and can be used in the treatment of rhinosinusitis diseases.


Competition between chylomicrons and their remnants for plasma removal: a study with artificial emulsion models of chylomicrons.
In previous studies, protein-free emulsions of defined lipid composition were shown capable of simulating either the metabolism of chylomicrons (chylomicron-like emulsion) or their remnants (remnant-like emulsion), depending on the content of free, unesterified cholesterol. To validate further the assumption that remnant-like and chylomicron-like emulsion have metabolic pathways in common with their natural counterparts, studies of competition for plasma removal were undertaken: the remnant-like emulsion labeled with [3H]triolein was injected sequentially twice in the carotid arteries of rats to compare the clearance of remnant-like emulsion of the second injection with the first (control). Prior to the second injection, a large bolus of the chylomicron-like emulsion or rat lymph chylomicron was injected, to check the hypothesis that remnant generated from chylomicron-like emulsion or natural chylomicrons could compete with and displace remnant-like emulsion particles from their tissue receptor sites. Experiments were also performed in rats treated with Triton WR-1339, to block the generation of remnants. Results showed that remnants derived from either natural chylomicrons or chylomicron-like emulsion both strongly competed with the remnant-like emulsion. In contrast, when transformation of remnants was prevented by Triton, the undegraded particles of chylomicron-like emulsion or natural chylomicron were unable to compete with or displace remnant-like emulsion from its sites of removal from the plasma. In agreement with plasma clearance data, the hepatic uptake of the remnant-like emulsion was inhibited by the surplus dose of natural chylomicrons. In contrast, the spleen uptake was unaffected by it.


Population genetics and host specificity of Varroa destructor mites infesting eastern and western honeybees.
In a globalized world, parasites are often brought in contact with new potential hosts. When parasites successfully shift host, severe diseases can emerge at a large cost to society. However, the evolutionary processes leading to successful shifts are rarely understood, hindering risk assessment, prevention, or mitigation of their effects. Here, we screened populations of Varroa destructor, an ectoparasitic mite of the honeybee genus Apis, to investigate their genetic structure and reproductive potential on new and original hosts. From the patterns identified, we deduce the factors that influenced the macro- and microevolutionary processes that led to the structure observed. Among the mite variants identified, we found two genetically similar populations that differed in their reproductive abilities and thus in their host specificity. These lineages could interbreed, which represents a threat due to the possible increased virulence of the parasite on its original host. However, interbreeding was unidirectional from the host-shifted to the nonshifted native mites and could thus lead to speciation of the former. The results improve our understanding of the processes affecting the population structure and evolution of this economically important mite genus and suggest that introgression between shifted and nonshifted lineages may endanger the original host. The online version contains supplementary material available at 10.1007/s10340-020-01322-7.


Long-Term Follow-Up of the Repair of the Multiple-Branch Facial Nerve Defect Using Acellular Nerve Allograft.
To assess the clinical efficacy of the repair of facial nerve defects by allograft transplantation using acellular facial nerves. Seven patients with facial nerve defects, ranging from damage to 1 facial nerve branch to combined defects of all branches, were enrolled. Defects ranged from 3 to longer than 4 cm. All defects were repaired by transplantation of acellular facial nerve allografts. Static and dynamic symmetry and facial expressions were evaluated using the House-Brackmann classification and the functional status of the facial nerve was assessed electromyographically. No patient received immunosuppressive therapy. All wounds healed well, with no swelling or inflammatory exudation. The patients recovered facial nerve function to various extents. Six months postoperatively, 4 of 7 patients showed static facial asymmetry. Twelve months postoperatively, 3 patients had static facial asymmetry with normal eye closure, and only careful observation could detect slight asymmetry of forehead movement. Two of 7 patients showed moderate facial nerve dysfunction. Ipsilateral facial movement and facial asymmetry were obvious in the patient whose defect affected the common trunk and all facial nerve branches. Two years postoperatively, 5 of 7 patients had mild facial nerve dysfunction, with symmetric faces and incomplete eye occlusion. Six years postoperatively, these patients continued to show symmetric faces and incomplete ipsilateral eye occlusion, but facial muscle function was considerably restored. Follow-up electromyography showed neurologic recovery in all patients. The repair of a facial nerve defect by transplantation of an acellular facial nerve allograft is feasible.


Evidence that phorbol ester-activated pathways are not directly involved in the action of insulin in rat adipocytes.
The effects of 12-phorbol 13-myristate acetate (PMA) on glucose transport, glucose metabolism and lipolysis in rat adipocytes were examined. Alone, PMA (100 ng/ml) stimulated 2-deoxyglucose transport, glucose oxidation and lipogenesis by an amount corresponding to about 30-50% of the maximal insulin effect. The effect of PMA on the insulin-stimulated processes was additive at all insulin concentrations. Adenosine deaminase-stimulated lipolysis was enhanced by about 50% by PMA (100 ng/ml). Thus, in contrast to insulin, PMA had a lipolytic effect. The antilipolytic effect of insulin was unaffected by the presence of PMA, both ED50 and maximal inhibition of insulin were unchanged. In conclusion, it is suggested that phorbol esters may activate pathways other than those activated by insulin in rat adipocytes.


Immature Reticulocyte Fraction and Absolute Neutrophil Count as Predictor of Hemopoietic Recovery in Patients with Acute Lymphoblastic Leukemia on Remission Induction Chemotherapy.
Acute lymphoblastic leukemia (ALL) encompasses a group of lymphoid neoplasms that are more common in children and arise from B-and T-lineage lymphoid precursor cells. The immature reticulocyte fraction (IRF), a new routine parameter in hematology analyzers, can give an indication of hemopoietic recovery like absolute neutrophil count (ANC). The purpose of this study was to evaluate IRF in excess of 5% was considered as IRF recovery. In this descriptive study, 2.5 to 3 mL of EDTA blood of 45 ALL patients undergoing the remission induction phase of their treatment was sampled and analyzed with a Sysmex XE-5000 on day 1 and every second day thereafter until the day of recovery. ANC of >0.5x109/L on the day corresponding to the first of the three consecutive counts was considered as the day of ANC recovery. IRF recovery was an IRF in excess of 5%. The mean age of the patients was 12.04±5.30 years; 25 patients (55.6%) were male and 20 patients (44.4%) were female. On day 1 of induction remission, the mean IRF value was 9.68±1.41, while the mean ANC value was 0.077±0.061. Mean recovery day for IRF was 11.84±7.44 and mean recovery day for ANC was 17.67±8.77 (two- tailed p-value <0.0001 with 95% confidence interval). By day 28, out of 45 patients 36 (80%) showed ANC recovery, while 41 (91%) showed IRF recovery. The remaining patients who had not shown recovery by day 28 were further followed up and all of them showed recovery of both parameters by day 39. This study concluded that postinduction bone marrow hemopoietic recovery was earlier by IRF than ANC in children with ALL on chemotherapy.


Synthesis of 13C-dehydrocoelenterazine and model studies on Symplectoteuthis squid bioluminescence.
In the photoprotein of an Okinawan squid bioluminescence of Symplectoteuthis oualaniensis L a dehydrocoelenterazine has been assigned as a chromophoric precursor to its apoprotein. To prove this mechanism, we have established new synthetic route to ca. 100%-13C incorporated dehydrocoelenterazine and coelenterazine at the neighboring carbon of the 2-position of 2,3-dihydroimidazo-[1,2a]-pyrazinone skeleton. This 13C enriched dehydrocoelenterazine readily converted in equilibrium between its adduct forms as a diastereomixture with glutathione (GSH) or dithiothreitol (DTT) compounds having sulfhydryl group. Structures of such adducts were fixed under acidic conditions and then discussed by NMR spectroscopy as well as absorbance and fluorescence spectra.


Prevalence of lower urinary tract symptoms in school-age children.
Epidemiological studies have demonstrated rates of incontinence and enuresis as high as 20% in school-age children. This cross-sectional study aimed to investigate the prevalence of lower urinary tract (LUT) symptoms in 739 children aged 6-12 years enrolled in three government schools with different socioeconomic levels in Minas Gerais, Brazil. Symptoms of LUT were evaluated using a modified version of the Dysfunction Voiding Scoring System in which the cutoff point considered as an indicator of LUT dysfunction is >6 for girls and >9 for boys. Children with a score indicative of symptoms received an educational booklet on the functioning of the LUT and were sent for clinical evaluation. LUT dysfunction symptoms were detected in 161 (21.8%) children. Symptoms were most frequent in girls (p < 0.001), children aged 6-8 (p < 0.028), and attended the school with the lowest social level (p < 0.001). Intestinal constipation was the most prevalent finding (30.7%), independent of LUT score. The most common urinary symptoms in children with an elevated score were diurnal urinary incontinence (30.7%), holding maneuvers (19.1%), and urinary urgency (13.7%). Stress factors were associated in 28.4% of children. Our findings suggest that LUT symptoms must be investigated carefully at routine pediatric visits.


Blockade of virus infection by human CD4+ T cells via a cytokine relay network.
CD4(+) T cells directly participate in bacterial clearance through secretion of proinflammatory cytokines. Although viral clearance relies heavily on CD8(+) T cell functions, we sought to determine whether human CD4(+) T cells could also directly influence viral clearance through cytokine secretion. We found that IFN-gamma and TNF-alpha, secreted by IL-12-polarized Th1 cells, displayed potent antiviral effects against a variety of viruses. IFN-gamma and TNF-alpha acted directly to inhibit hepatitis C virus replication in an in vitro replicon system, and neutralization of both cytokines was required to block the antiviral activity that was secreted by Th1 cells. IFN-gamma and TNF-alpha also exerted antiviral effects against vesicular stomatitis virus infection, but in this case, functional type I IFN receptor activity was required. Thus, in cases of vesicular stomatitis virus infection, the combination of IFN-gamma and TNF-alpha secreted by human Th1 cells acted indirectly through the IFN-alpha/beta receptor. These results highlight the importance of CD4(+) T cells in directly regulating antiviral responses through proinflammatory cytokines acting in both a direct and indirect manner.


A possibe alpha-adrenergic mechanism for drug (CRL 40028)-induced hyperactivity.
CRL 40028 (benzhydryl sulfinyl acetohydroxamic acid)-induced stimulation in mice, measured as an increase in locomotor activity was studied following an intraperitoneal injection of drugs known to block alpha-adrenergic receptors. Phenoxybenzamine (20 mg/kg), prazosin (0.5-1 mg/kg) and yohimbine (2 mg/kg) prevented the development of CRL 40028-induced hyperactivity. These results suggest that stimulation of an alpha-adrenergic postsynaptic receptor is of importance for the stimulant effect of CRL 40028.


The melanocyte. Its structure, function, and subpopulations in skin, eyes, and hair.
I would like to stress that there seem to be three subpopulations of neural crest-derived melanocytes in the body that can be functionally and morphologically distinguished: the cutaneous melanocytes, which continuously synthesize small melanosomes to be transferred to keratinocytes; the uveal melanocytes, which synthesize larger melanosomes for only a short while to be retained by this melanogenically dormant cell; and the hair melanocyte, which intermittently produces melanin either in a cyclic manner or as a periodic supply from a stem population. These three types of melanocytes synthesize melanin granules by an identical bipartite system. However, the control mechanism regulating the specific differentiation and postmelanin synthesis function of these cell types needs to be addressed in future research.


High immunohistochemical nestin expression is associated with greater depth of infiltration in dermatofibrosarcoma protuberans: a study of 71 cases.
Dermatofibrosarcoma protuberans (DFSP) was recently shown to express nestin, a marker that has been associated with poorer prognosis when present in high levels in certain tumors. The objective of this study is to explore the association between high nestin expression and deep invasion. We performed a retrospective, observational study in which we evaluated the degree of nestin expression in 71 DFSP. The odds of fascial involvement was calculated before and after adjusting for the following confounders: age, sex, tumor size, time to diagnosis, tumor site, the presence of fibrosarcomatous areas, pleomorphism, number of mitotic figures and predominant histopathologic pattern. We also calculated the Spearman Rho correlation coefficient between nestin staining intensity and depth of invasion. Nestin immunopositivity was found in 98.6% of the tumors, and high expression levels were significantly associated with invasion of the fascia. The odds of fascial involvement in tumors with strong nestin staining was 6.56 (p = 0.001) before adjustment for confounders and 14.86 after adjustment (p = 0.007). The Spearman rho correlation coefficient between nestin expression and deep invasion was 0.287 (p = 0.015). High inmunohistochemical nestin expression appears to be associated with deeper invasion in DFSP.


Risk factors for tumor recurrence and progression of spindle cell oncocytoma of the pituitary gland: a systematic review and pooled analysis.
Spindle cell oncocytoma (SCO) is an extremely rare sellar neoplasm. No observational studies have been reported so far to investigate the prognostic factors of this tumor entity. This systematic review aimed to elucidate the risk factors for tumor recurrence/progression of SCO. We searched for relevant articles in PubMed and Web of Science. Studies providing individual patient data with follow-up information of SCO cases were included. Pearson's Chi square and Fisher's exact test were used for categorical variables while t test or Mann-Whitney tests were applied for continuous variables, if applicable. We used the Cox regression model to assess the effects of suspected variables on progression-free survival (PFS). A total of 38 case reports and case series comprising of 67 SCOs were included for final analyses. Recurrent/progressive tumors were noted in 38.8% of cases. Among the clinicopathological factors, only the extent of surgery was a significant risk factor for tumor recurrence/progression. SCO patients with a subtotal resection had a significantly higher risk for tumor relapse in comparison with complete removal (HR 7.51; 95% CI 1.75-32.31; p = 0.007). Our study demonstrated the characteristic clinicopathological features of SCOs with a high recurrence/progression rate and outlined the predictor for tumor relapse. Failure to achieve gross total resection is the only risk factor for tumor recurrence/progression.


Transcriptomic and metabolomic analysis reveals the potential mechanisms underlying the improvement of β-carotene and torulene production in Rhodosporidiobolus colostri under low temperature treatment.
Carotenoids are a group of versatile isoprenoid pigments widely utilized in the food, pharmaceutical and cosmetic industries. Rhodosporidiobolus colostri is a cold-adapted yeast that has piqued interest as a natural source of microbial carotenoids, including β-carotene, torulene and torularhodin. Here, the effect of low temperature on carotenoid production in R. colostri was investigated. The results indicated that the total carotenoid production was significantly increased at the low temperature (16 ℃) treatment (29.016 mg/L) as compared to control (25 ℃) (17.147 mg/L) after 5 days of cultivation. Among them, the increase in β-carotene and torulene serve as the main contributors to the improvement in total carotenoid production. Integrative analyses of the transcriptome and metabolome suggested that the up-regulation of the terpenoid backbone biosynthesis pathway and the down-regulation of the TCA cycle flux allow more acetyl-CoA to be diverted to carotenogenesis, which might be the reason for the increased production of β-carotene and torulene in R. colostri under low temperature treatment. Our results presented herein should not only provide an effective strategy for increasing total carotenoids production in R. colostri, but lay the molecular groundwork to further facilitate genetic engineering to enhance the yield of certain carotenoids.


The L-type calcium channel Cav1.3 is required for proper hippocampal neurogenesis and cognitive functions.
L-type voltage gated Ca(2+) channels (LTCCs) are widely expressed within different brain regions including the hippocampus. The isoforms Cav1.2 and Cav1.3 have been shown to be involved in hippocampus-dependent learning and memory, cognitive functions that require proper hippocampal neurogenesis. In vitro, functional LTCCs are expressed on neuronal progenitor cells, where they promote neuronal differentiation. Expression of LTCCs on neural stem and progenitor cells within the neurogenic regions in the adult brain in vivo has not been examined so far, and a contribution of the individual isoforms Cav1.2 and Cav1.3 to adult neurogenesis remained to be clarified. To reveal the role of these channels we first evaluated the expression patterns of Cav1.2 and Cav1.3 in the hippocampal dentate gyrus and the subventricular zone (SVZ) in adult (2- and 3-month old) and middle-aged (15-month old) mice on mRNA and protein levels. We performed immunohistological analysis of hippocampal neurogenesis in adult and middle-aged Cav1.3(-/-) mice and finally addressed the importance of Cav1.3 for hippocampal function by evaluating spatial memory and depression-like behavior in adult Cav1.3(-/-) mice. Our results showed Cav1.2 and Cav1.3 expression at different stages of neuronal differentiation. While Cav1.2 was primarily restricted to mature NeuN(+) granular neurons, Cav1.3 was expressed in Nestin(+) neural stem cells and in mature NeuN(+) granular neurons. Adult and middle-aged Cav1.3(-/-) mice showed severe impairments in dentate gyrus neurogenesis, with significantly smaller dentate gyrus volume, reduced survival of newly generated cells, and reduced neuronal differentiation. Further, Cav1.3(-/-) mice showed impairment in the hippocampus dependent object location memory test, implicating Cav1.3 as an essential element for hippocampus-associated cognitive functions. Thus, modulation of LTCC activities may have a crucial impact on neurogenic responses and cognition, which should be considered for future therapeutic administration of LTCCs modulators.


Written consent - a prospective audit of practices for ENT patients.
It is very important that patients are given sufficient time to consider the implications of surgical treatment. The authors audited the consenting practices for patients undergoing surgery in a busy ENT unit. The first cycle demonstrated that 15% of patients were providing written consent for surgery on the same day as their operation. Subsequent to a simple change in departmental policy, this was reduced to 2%. The medicolegal implications of this audit are discussed with reference to current recommendations. This simple policy change not only protects the hospital trust from potential litigation but also provides a smooth journey for the patients from diagnosis to making the decision to operate and finally to undergoing surgery.


Modular and efficient synthesis of a poly (propylene imine) (PPI) dendron applied to acid-sensitive doxorubicin conjugation.
The shorter synthesis of a novel poly(propylene imine) (PPI) dendron that can be quantitatively conjugated in good yields in a modular fashion to various modified Michael acceptors is reported herein. The focal point of the PPI dendron was coupled to an ester-linked thioctic acid-modified spacer to allow for an improved scalable synthesis and to allow attachment to other suitable systems, such as nanoparticle surfaces. The two modified Michael acceptors reported here are an acyl hydrazine Michael acceptor as well as an azide Michael acceptor. The acyl hydrazine modified third generation PPI dendron was further conjugated to doxorubicin (DOX) as a model system to test acid-sensitive drug delivery. The PPI-DOX conjugate displayed fast release of DOX at pH 4.5 while remaining stable at pH 7.4 and the PPI-DOX conjugate showed low in vitro cytotoxicity against PC3 prostate cancer cells. This modular platform represents a powerful dendronized system for incorporation onto nanoparticles or other systems to allow for multifunctional drug delivery.


The Course of Superficial Temporal Artery in Patients with Microtia and its Relationship with the Remnant.
Temporoparietal fascia is important for auricular reconstruction or repair after auricular reconstruction. Thus, the course of the superficial temporal artery (STA) is of vital importance to prevent destruction of the artery. The purpose of this study was to evaluate the course of the superficial temporal artery in patients with congenital microtia and its relationship with remnants. This was a prospective study. Patients with microtia who underwent auricular reconstruction in our hospital from January 2021 to July 2021 underwent ultrasound examination of the STA. Under the guidance of ultrasound, the superficial temporal artery and its branches were located and marked on the body surface before the operation, ranging from the zygomatic arch plane to the temporal parietal artery. In addition, the hemodynamics of the STAs were recorded. A total of 108 patients with microtia were collected, including 106 patients with unilateral microtia and 2 patients with bilateral microtia. There were 82 cases of lobule type, 21 cases of small concha type, and 7 cases of large concha type. The superficial temporal artery in 103 ears was divided into two branches: the parietal branch and the frontal branch, but there was only one branch in 7 ears. The parietal branch was absent in 5 cases, and the frontal branch was absent in 2 cases. In most of the ears, the bifurcation was located above the zygomatic arch plane. Only in 2 ears was the bifurcation located below the zygomatic arch, and the most common bifurcation position was the eyebrow arch level (43.7%). Regarding the shortest distances between the STA and the remnant, they were less than 0.5 cm in 47 ears, more than 1 cm in 30 ears, and 0.5 cm to 1 cm in 33 ears. The course of STA varied greatly and there were occasional single branches. The distances between the STA and remnant were often near 0.5 cm by ultrasonography. Therefore, when removing the remnant and separating the pocket, care should be taken to avoid arterial injury. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Prognosticating brain tumor patient survival after laser thermotherapy: Comparison between neuroradiological reading and semi-quantitative analysis of MRI data.
Given increasing interest in laser interstitial thermotherapy (LITT) to treat brain tumor patients, we explored if examining multiple MRI contrasts per brain tumor patient undergoing surgery can impact predictive accuracy of survival post-LITT. MRI contrasts included fluid-attenuated inversion recovery (FLAIR), T1 pre-gadolinium (T1pre), T1 post-gadolinium (T1Gd), T2, diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC), susceptibility weighted images (SWI), and magnetization-prepared rapid gradient-echo (MPRAGE). The latter was used for MRI data registration across preoperative to postoperative scans. Two ROIs were identified by thresholding preoperative FLAIR (large ROI) and T1Gd (small ROI) images. For each MRI contrast, a numerical score was assigned based on changing image intensity of both ROIs (vs. a normal ROI) from preoperative to postoperative stages. The fully-quantitative method was based on changing image intensity across scans at different stages without any human intervention, whereas the semi-quantitative method was based on subjective criteria of cumulative trends across scans at different stages. A fully-quantitative/semi-quantitative score per patient was obtained by averaging scores for each MRI contrast. A standard neuroradiological reading score per patient was obtained from radiological interpretation of MRI data. Scores from all 3 methods per patient were compared against patient survival, and re-examined for comorbidity and pathology effects. Patient survival correlated best with semi-quantitative scores obtained from T1Gd, ADC, and T2 data, and these correlations improved when biopsy and comorbidity were included. These results suggest interfacing neuroradiological readings with semi-quantitative image analysis can improve predictive accuracy of patient survival.


Changes in fitness and shipboard task performance following circuit weight training programs featuring continuous or interval running.
Pre- and post-physiological data were collected on 57 Navy men (mean age = 19.5 years) who participated in either circuit weight training/continuous run (CWT/CR) (N = 31) or circuit weight training/interval run (CWT/IR) (N = 26) programs. Measured variables included 4 measures of upper torso dynamic strength (one repetition maximum [1 RM] for arm curl, bench press, shoulder press, and lat pull-down); two measures of lower torso dynamic strength (1 RM) for knee extension and leg press); one measure of power (number of revolutions completed on an arm ergometer (Monark) at maximum drag); three measures of muscular endurance (number of repetitions at 60% 1 RM for bench press and leg press and maximal number of bent-knee sit-ups in 120 s); one stamina measure (time to exhaustion on a cycle ergometer (Monark) maximal work capacity [MWC] test; and three simulated shipboard tasks: manikin shoulder drag, open/secure a water tight door and paint bucket carry. Composite shipboard performance derived from the summed time (s) required to complete the three tasks was also calculated. Results show performance on the manikin shoulder drag and majority of evaluative fitness measures was significantly (p less than 0.05) enhanced following both circuit weight training/run formats. Significantly (p less than 0.05) higher values for shoulder press (F = 7.2), arm ergometer (F = 5.3), and sit-ups (F = 6.8) and lower values for leg press muscular endurance (F = 5.1) were observed in CWT/IR when compared to CWT/CR.(ABSTRACT TRUNCATED AT 250 WORDS)


Grade and looseness of the inner cell mass may lead to the development of monochorionic diamniotic twins.
To examine the relationship between the inner cell mass (ICM) grade and its morphological configuration on the occurrence of monochorionic diamniotic (M-D) twinning. Retrospective embryo cohort study. Private IVF clinic. Evaluation of frozen-thawed single blastocyst transfers with hormone replacement treatment in 8,435. This cohort included 71 blastocysts and their ICMs observed by time-lapse photography. Any changes in configuration of the ICMs observed by time-lapse photography were analyzed retrospectively. The amount of loosening of blastomeres within the ICM was evaluated by time-lapse observations. The number of cells that were involved in the loosening process was also assessed. Both of these parameters were correlated with the type of monozygotic twinning that eventuated. The M-D twinning incidence resulting from blastocysts with a high grade ICM (grade A) were transferred was 0.38% (3/796), whereas it was significantly higher, 1.38% (34/2,463), when blastocysts with a poorer (B and C) grade ICM were transferred. Among 71 transferred frozen-thawed blastocysts that were studied with time-lapse photography, there were two dichorionic diamniotic and one M-D twins. Careful observations of the embryo that resulted in the one M-D case, revealed that the ICM acquired a looser appearance due to decompaction of at least eight cells. This type of decompaction was not observed in the ICMs of other transferred blastocysts. The occurrence of M-D twinning may be avoided by excluding blastocysts that contain decompacting ICMs.


Item analysis of a single response dichotic listening test.
Ten left-handed and eight right-handed subjects were tested on five replications of a single-response dichotic listening test. Nine CV dichotic pairings of the six stop consonants plus /a/ were used. Computer synthesis guaranteed that these pairs differed on only a single phonemic feature, thus permitting fusion. Mean laterality scores were significantly higher (greater right ear advantage) for right-handers than for left-handers. Selective attention instructions did not alter laterality scores. Test-retest correlation coefficients were consistently high (greater than .70 for all adjacent replication comparisons). Error rates were low (averaging 5.5%) and 39% of these were psychoacoustic confusions rather than true (guessing) errors. These confusions were found for only two of the nine pairs. Stimulus dominance, as opposed to ear dominance, was considered separately. Two dichotic pairs had such strong stimulus dominance for all subjects that little ear advantage information was available from those pairs. It was recommended that the three dichotic pairs prone to psychoacoustic confusions and/or overwhelming stimulus dominance be removed from the test.


Immunohistochemical expression of the ERG gene in prostatic adenocarcinoma and its relationship with clinicopathological parameters.
This study aimed to determine the immunohistochemical expression of the ERG gene in prostatic adenocarcinoma and to evaluate the relationships between ERG expression and clinicopathological parameters. Cross-sectional study. Pathology department of a tertiary hospital. The prostatectomy materials of 122 patients diagnosed with prostate adenocarcinoma between 2004 and 2017 in Zonguldak Bülent Ecevit University Faculty of Medicine, Department of Pathology were included in the study. Clinical data were obtained from patient files and macroscopic data were obtained from surgery and pathology reports. ERG expression, age, prostate-specific antigen levels, Gleason pattern and score, Gleason grade, and pathological stage were recorded. The mean age of the patients was 62.66 ± 5.81 years and overall preoperative PSA was 10.40 ± 8.88 ng/ml. ERG was positive in 52.46% of the patients. PSA levels were similar in ERG positive and negative samples (p = 0.935). There was no significant relationship between Gleason score and ERG positivity (p = 0.197). ERG expression did not change with regard to age groups (p = 0.441) or tumour stage (p = 0.371). This study shows that the frequency of ERG positivity was high in our patients and that ERG positivity was not associated with clinical and pathological features, such as PSA levels, Gleason score, age and pathological stage.


Paediatric brain-stem gliomas: MRI, FDG-PET and histological grading correlation.
MRI and FDG-PET may predict the histological grading of paediatric brain-stem gliomas. To assess MRI findings and metabolic imaging using FDG-PET of brain-stem gliomas based on histological grading. Included in the study were 20 paediatric patients (age 3-14 years, mean 8.2 years) with brain-stem glioma (five glioblastomas, ten anaplastic astrocytomas and five low-grade astrocytomas). MR images were assessed for the anatomical site of tumour origin, focality, pattern of tumour growth, and enhancement. All glioblastomas were located in the pons and showed diffuse pontine enlargement with focally exophytic features. Eight anaplastic astrocytomas were located in the pons and demonstrated diffuse pontine enlargement without exophytic features. Low-grade astrocytomas were located in the pons, midbrain or medulla and showed focally exophytic growth features and peripheral enhancement. In 12 patients in whom FDG-PET was undertaken, glioblastomas showed hypermetabolic or hypometabolic lesions, anaplastic astrocytomas showed no metabolic change or hypometabolic lesions and low-grade astrocytomas showed hypometabolism compared with the cerebellum. MRI findings correlated well with histological grading of brain-stem gliomas and MRI may therefore predict the histological grading. FDG-PET may be helpful in differentiating between anaplastic astrocytoma and glioblastomas among high-grade tumours.


Age-related differences in bimanual coordination performance.
Purpose. The purpose of this article was to determine how characteristics of bimanual coordination tasks affect the quality of performance and to determine the impact of these characteristics on muscular activation of the upper limbs, with consideration of age-related differences. Methods. The research was carried out on two groups consisting of 25 people aged 20-30 and 60-67 years. The subjects performed seven tasks that varied in coordination mode, tracking mode and outline-tracing. The main measures of task performance were calculated on the basis of the difference between the position of the target and tracing cursors. Cohen's d value was calculated to show differences in measures between groups. Results. There were higher values of error and variability measures for elderly people compared to young. Complex tasks showed the largest difficulty, which suggests that, when performed, such tasks have the greatest potential to improve coordination skills. Tasks during which both limbs contribute to the movement of one cursor proved the most appropriate. Conclusion. The tracking mode is of great importance for the quality of performance in motor coordination tasks, while the performance of tasks with imposed speed is much more strongly age-sensitive than performance with a freely chosen speed.


The effect of paclitaxel on gene expression and activity of arylamine N-acetyltransferase and DNA-2-aminofluorene adduct formation in human leukemia HL-60 cells.
N-Acetylation is recognized as the first step in arylamine metabolism. The enzyme responsible for N-acetylation is called arylamine N-acetyltransferase (NAT),which uses acetyl coenzyme A as the acetyl group donor. Paclitaxel has been shown to exhibit antineoplastic and anticancer activity. In this study, paclitaxel was selected to determine the inhibition of arylamine N-acetyltransferase activity, gene expression (NAT mRNA) and DNA-2-aminofluorene adduct formation in human leukemia HL-60 cell line. Paclitaxel (0.01-l microM) did decrease the level of NAT mRNA in a dose-dependent manner. The results demonstrated that paclitaxel inhibited NAT activity and DNA-2-aminofluorene adduct formation in human leukemia HL-60 cells in a dose-dependent manner. Using standard steady-state kinetic analysis, it was demonstrated that paclitaxel was a possible uncompetitive inhibitor to NAT activity in cytosols based on the decrease in apparent values of K(m) and V(max). This report is the first demonstration that paclitaxel affected human leukemia HL-60 cells NAT activity and DNA-2-aminofluorene adduct formation.


Effects of phycocyanin on INS-1 pancreatic β-cell mediated by PI3K/Akt/FoxO1 signaling pathway.
The level of methylglyoxal (MG), which is a side-product of metabolic pathways, particularly in glycolysis, is elevated in diabetes. Notably, the accumulation of MG causes a series of pathological changes. Phycocyanin (PC) has been demonstrated to show insulin-sensitizing effect, however, the underlying molecular mechanism remains elusive. The aim of this study was to investigate the protective effects of PC on INS-1 rat insulinoma β-cell against MG-induced cell dysfunction, as well as the underlying mechanisms. PC was preliminarily verified to time-dependently activate PI3-kinase (PI3K) pathway, but the PI3K-specific inhibitor Wortmannin blocked the effect of PC. Glucose-stimulated insulin secretion (GSIS) was impaired in MG-treated INS-1 cells. Furthermore, MG induced dephosphorylation of Akt and FoxO1, resulting in nuclear localization and transactivation of FoxO1. Nevertheless, these effects were all effectively attenuated by PC. The ameliorated insulin secretion was related to the changes of FoxO1 mediated by PC, which demonstrated by RNA interference. And, the dosage used in the above experiments did not affect β-cell viability and apoptosis, although long-term MG induced cell apoptosis and mitochondrial dysfunction. In conclusion, PC was capable to protect INS-1 pancreatic β-cell against MG-induced cell dysfunction through modulating PI3K/Akt pathway and the downstream FoxO1.


Reserpine-induced supersensitivity to the activation of cardiac glycogen phosphorylase by calcium.
Rats receiving reserpine (2.5 mg/kg, 24 h before sacrifice) developed a supersensitivity to the phosphorylase activating effect of both noradrenaline and Ca2+. Supersensitivity to the inotropic and chronotropic effects of the agonists did not develop with this dose of reserpine. It is concluded that reserpine induced supersensitivity, as well as being dose and species dependent, is also dependent on the response measured. It is concluded further that the supersensitivity developed to noradrenaline may be due to an alteration in the responding system (in this case the phosphorylase activating system) to calcium.


Genetic analysis of Japanese patients with myophosphorylase deficiency (McArdle's disease): single-codon deletion in exon 17 is the predominant mutation.
We report molecular genetic analysis of 11 Japanese patients with myophosphorylase deficiency (McArdle's disease). Four reported mutations, frequently observed in patients with McArdle's disease, in exons 1, 5, 14 and 17 were investigated. Seven patients out of 11 were homozygous for a single-codon deletion at codon 708/709 in exon 17 and one patient was heterozygous for a single-codon deletion with an unknown mutant allele. In contrast, the predominant mutation reported in US and UK patients (CGA to TGA at codon 49 in exon 1), accounting for 75% and 83% of the cases, respectively, was not found in any of the Japanese patients. Results suggest that the predominant mutation in Japanese patients is a single-codon deletion at codon 708/709 in exon 17 (found in 73% of our patients) and differs from the most common mutation in US or UK patients.


Channel Confinement of Aromatic Petrochemicals via Aryl-Perfluoroaryl Interactions With a B←N Host.
We report channel confinement properties of an electron-deficient boron host derived from the orthogonal B←N interaction between a boronic ester and trans-pentafluorostilbazole. The boron host forms one-dimensional channels in the crystalline solid state when crystallized with common electron-rich aromatic petrochemicals (i.e., benzene, toluene, o-xylene) to form solvates and a cocrystal with stilbene. Molecular confinement of the electron-rich molecules in the solids is achieved through a combination of aryl-perfluoroaryl interactions (π-πF) and hydrogen bonds.


Arterial blood gas sampling using a modified standard plastic syringe.
A simple modification of the standard plastic syringe is described which converts it into a self-filling system under arterial pressure. This overcomes one of the common errors in arterial blood gas sampling.