Differential expression of MART-1, tyrosinase, and SM5-1 in primary and metastatic melanoma.
The new monoclonal antibody SM5-1 has been shown to have significant advantages in immunohistochemistry of melanoma over currently used antibodies such as HMB-45 or anti-S100. In this study we compared the immunohistological staining pattern of SM5-1 with that of the more recently described antibodies A103 (anti-MART-1) and T311 (anti-Tyrosinase) in 344 paraffin-embedded melanoma specimens, consisting of 101 primary melanomas (77 SSM, 16 NM, 6 ALM, 2 LMM) and 243 melanoma metastases. The overall reactivity of SM5-1 for all the specimens was 92% (318/344) compared with 83% (285/344) for MART-1 and 71% (245/344) for Tyrosinase. Staining of melanoma metastases with SM5-1 was found in 91% (222/243), but only in 77% (187/243) with A103 and 63% (154/243) with T311, respectively. Staining with SM5-1 was more homogenous with 196 of 243 (80%) of metastatic lesions showing 50% or more positively stained cells within the lesions, whereas A103 and T311 did so in 141 of 243 (58%) or 117 of 243 (48%) of the lesions. With regard to staining intensity of SM5-1, 157 of 243 (64%) showed a strong or very strong staining intensity, whereas A103 and T311 did so in 85 of 243 (35%) or 70 of 243 (29%) of the lesions. Staining intensity and percentage positivity correlated well for SM5-1, because from the 58 very strong positive metastases 55 showed staining in more than 75% of the cells within a lesion. Importantly, 52 of 56 MART-1-negative metastases and 81 of 89 Tyrosinase-negative metastases were positive for SM5-1. Thirty-eight metastases (15.6%) were negative for both A103 and T311. Of those, 35 (92.1%) were positive for SM5-1, demonstrating the value of SM5-1 in identifying melanoma-associated antigen-negative lesions. We conclude that SM5-1 could be of value in immunohistochemistry of melanoma.


Kinetic studies on the hepatic microsomal metabolism of dimethylnitrosamine, diethylnitrosamine, and methylethylnitrosamine in the rat.
The oxidative dealkylation of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), and methylethylnitrosamine (MEN) by Sprague-Dawley rat liver microsomes was studied by a colorimetric assay for the simultaneous analysis of formaldehyde and acetaldehyde. Dealkylation in each instance followed Michaelis-Menten kinetics, but the Michaelis constant (Km) for DEN was an order of magnitude smaller than the Km for DMN. Km values for demethylation and deethylation of MEN were intermediate between those for DMN and DEN. DMN inhibited-deethylase, and DEN inhibited DMN-demethylase activity. The inhibition was of a mixed type in both instances.


Obstetrics services--women's perspectives.
To obtain women's views of obstetric care 400 randomly selected mothers were interviewed postnatally. Since family planning is a constitutional right and all related services free of charge and virtually 100% of pregnant women attend the antenatal clinic, the questions asked were mainly oriented to evaluation of existing obstetric practice. Women were generally satisfied with labor and delivery care (71.2%), but as many as 88.2% of them expressed their dissatisfaction with postnatal care practice. Our women opted for optimal hospital perinatal care - a home-like postnatal care, possibilities for better bonding between mothers and newborn infants and more open, individually oriented communication with medical staff.


Effect of phospholipase digestion and lysophosphatidylcholine on dopamine receptor binding.
[3H]Spiperone specific binding by microsomal membranes isolated from sheep caudate nucleus is decreased by trypsin and phospholipase A2 (Vipera russeli), but is insensitive to neuraminidase. The inhibitory effect of phospholipase A2 is correlated with phospholipid hydrolysis. After 15 min of phospholipase (5 micrograms/mg protein) treatment, a maximal effect is observed; the maximal lipid hydrolysis is about 56% and produces 82% reduction in [3H]spiperone binding. Equilibrium binding studies in nontreated and treated membranes showed a reduction in Bmax from a value of 388 +/- 9.2 fmol/mg protein before phospholipase treatment to a value of 52 +/- 7.8 fmol/mg protein after treatment, but no change in affinity (KD = 0.24 +/- 0.042 nM) was observed. Albumin washing of treated membranes removes 47% of lysophosphatidylcholine produced by phospholipid hydrolysis without recovering [3H]spiperone binding activity. However, the presence of 2.5% albumin during phospholipase A2 action (1.5 micrograms/mg protein) prevents the inhibitory effect of phospholipase on [3H]spiperone binding to the membranes, although 28% of the total membrane phospholipid is hydrolysed. Lysophosphatidylcholine, a product of phospholipid hydrolysis, mimics the phospholipase A2 effect on receptor activity, but the [3H]spiperone binding inhibition can be reversed by washing with 2.5% defatted serum albumin. Addition of microsomal lipids to microsomal membranes pretreated with phospholipase does not restore [3H]spiperone stereospecific binding. It is concluded that the phospholipase-mediated inhibition of [3H]spiperone binding activity results not only from hydrolysis of membrane phospholipids, but also from an alteration of the lipid environment by the end products of phospholipid hydrolysis.


Services for parental stress reduction in a pediatric ICU.
The stress of having their child in an ICU can be alleviated by keeping parents informed, ensuring positive relationships between staff and parents, providing concrete services that meet parents' needs, and maximizing parental involvement in the care of their child. We interviewed the parents of 22 children cared for in a pediatric ICU to determine how well their needs were met by the staff and facilities. Responses confirmed the importance of the 4 interventions listed above and indicated a high degree of satisfaction. The results emphasized the need for ICU staff to introduce themselves repeatedly to parents and make certain parents know who is responsible for their child's care, and to encourage parents to ask questions about their child's illness and therapy.


Is inflammaging an auto[innate]immunity subclinical syndrome?
The low-grade, chronic, systemic inflammatory state that characterizes the aging process (inflammaging) results from late evolutive-based expression of the innate immune system. Inflammaging is characterized by the complex set of five conditions which can be described as 1. low-grade, 2. controlled, 3. asymptomatic, 4. chronic, 5. systemic, inflammatory state, and fits with the antagonistic pleiotropy theory on the evolution of aging postulating that senescence is the late deleterious effect of genes (pro-inflammatory versus anti-inflammatory) that are beneficial in early life. Evolutionary programming of the innate immune system may act via selection on these genetic traits. Here I propose that the already acquired knowledge in this field may pave the way to a new chapter in the pathophysiology of autoimmunity: the auto-innate-immunity syndromes. Indeed, differently from the well known chapter of conventional autoimmune diseases and syndromes where the main actor is the adaptive immunity, inflammaging may constitute the subclinical paradigm of a new chapter of autoimmunity, namely that arising from an autoimmune inflammatory response of the innate-immune-system, an old actor of immunity and yet a new actor of autoimmunity, also acting as a major determinant of elderly frailty and age-associated diseases.


A new species of Sphelodon Townes (Hymenoptera: Ichneumonidae: Banchinae) from Colombia.
The genus Sphelodon Townes has 13 described species, nine species from the Neotropical region, three species from the Nearctic region and one (Sphelodon phoxopteridis) that occurs in both regions. A new species, Sphelodon antioquensis sp. n. is described here. This is the first record of Sphelodon for Colombia. A key to Sphelodon species occurring in the Neotropical Region is provided.


The Coffee Berry Borer (Hypothenemus hampei) Invades Hawaii: Preliminary Investigations on Trap Response and Alternate Hosts.
In August 2010 the coffee berry borer, Hypothenemus hampei, was first reported to have invaded the Kona coffee growing region of Hawaii, posing a severe economic challenge to the fourth largest agricultural commodity in the State. Despite its long and widespread occurrence throughout the tropics as the most serious pest of coffee, there are still discrepancies in the literature regarding several basic aspects of berry borer biology relevant to its control. In Kona coffee plantations, we investigated the beetles' response to several trap and lure formulations, and examined the occurrence of beetles in seeds of alternate host plants occurring adjacent to coffee farms. While traps were shown to capture significant numbers of beetles per day, and the occurrence of beetles in alternate hosts was quite rare, the unique situation of coffee culture in Hawaii will make this pest extremely challenging to manage in the Islands.


miR-1207-3p Is a Novel Prognostic Biomarker of Prostate Cancer.
MicroRNAs (miRNAs) have been found to be dysregulated in prostate cancer (PCa). In this study, we investigated if miR-1207-3p is capable of distinguishing between indolent and aggressive PCa and if it contributes to explaining the disproportionate aggressiveness of PCa in men of African ancestry (moAA). A total of 404 patients with primary adenocarcinoma of the prostate were recruited between 1988 and 2003 at the Moffitt Cancer Center, Tampa, FL, USA. Patient clinicopathological features and demographic characteristics such as race were identified. RNA samples from 404 postprostatectomy prostate tumor tissue samples were analyzed by real-time quantitative reverse transcription polymerase chain reaction for the mRNA expression of miR-1207-3p. miR-1207-3p expression in PCa that resulted in overall death or PCa-specific death is significantly higher than in PCa cases that did not. The same positive correlation holds true for other clinical characteristics such as biochemical recurrence, Gleason score, clinical stage, and prostate-specific antigen level. Furthermore, miR-1207-3p expression was significantly less in moAA in comparison to Caucasian men. We also evaluated whether miR-1207-3p is associated with clinical outcomes adjusted for age at diagnosis and tumor stage in the modeling. Using competing risk regression, the PCa patients with a high miR-1207-3p expression (≥6 vs 3) had a high risk to develop PCa recurrence (hazard rate = 2.5, P < .001) adjusting for age at diagnosis and tumor stage. In conclusion, miR-1207-3p is a promising novel prognostic biomarker for PCa. Furthermore, miR-1207-3p may also be important in explaining the disproportionate aggressiveness of PCa in moAA.


Outcome of rituximab treatment in Japanese patients with ANCA-associated vasculitis in daily clinical practice: A two-centre study in Fukushima, Japan.
Rituximab (RTX) efficacy for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been reported in large randomized studies; however, the efficacy of RTX in Japanese AAV patients, especially the elderly, is not well known. We aimed to determine the clinical efficacy of RTX in Japanese AAV patients including elderly patients. This study included 78 AAV patients newly diagnosed with AAV and treated in Fukushima Medical University Hospital or Ohta-Nishinouchi Hospital from April 2004 to September 2019. Clinical records were retrospectively reviewed, and clinical efficacy and outcome (1-year survival) between the RTX treatment group (23 cases) and the conventional therapy group (immunosuppressive therapy other than RTX, 55 cases) were compared. We also analysed the clinical efficacy and outcome in elderly-onset (>75 years) AAV patients. The RTX group showed similar efficacy and 1-year survival compared to the conventional therapy group. Conversely, after 6 months of treatment, prednisolone doses significantly decreased in the RTX group compared to the conventional therapy group (p < 0.01). In the elderly-onset AAV patients, clinical efficacy and outcome were not significantly different. RTX was effective in Japanese AAV patients and may be useful for prompt tapering of prednisolone doses, even in elderly-onset AAV patients.


Inside the "African cattle complex": animal burials in the holocene central Sahara.
Cattle pastoralism is an important trait of African cultures. Ethnographic studies describe the central role played by domestic cattle within many societies, highlighting its social and ideological value well beyond its mere function as 'walking larder'. Historical depth of this African legacy has been repeatedly assessed in an archaeological perspective, mostly emphasizing a continental vision. Nevertheless, in-depth site-specific studies, with a few exceptions, are lacking. Despite the long tradition of a multi-disciplinary approach to the analysis of pastoral systems in Africa, rarely do early and middle Holocene archaeological contexts feature in the same area the combination of settlement, ceremonial and rock art features so as to be multi-dimensionally explored: the Messak plateau in the Libyan central Sahara represents an outstanding exception. Known for its rich Pleistocene occupation and abundant Holocene rock art, the region, through our research, has also shown to preserve the material evidence of a complex ritual dated to the Middle Pastoral (6080-5120 BP or 5200-3800 BC). This was centred on the frequent deposition in stone monuments of disarticulated animal remains, mostly cattle. Animal burials are known also from other African contexts, but regional extent of the phenomenon, state of preservation of monuments, and associated rock art make the Messak case unique. GIS analysis, excavation data, radiocarbon dating, zooarchaeological and isotopic (Sr, C, O) analyses of animal remains, and botanical information are used to explore this highly formalized ritual and the lifeways of a pastoral community in the Holocene Sahara.


Increasing expression of oxytocin and vasopressin receptors in the equine conceptus between Days 10 and 16 of pregnancy.
Oxytocin (OT) and arginine vasopressin (AVP) have been detected in the yolk sac of the pre-attachment equine conceptus. Therefore, we have assessed the presence of OT and AVP receptors in equine conceptuses between Days 10 and 16 of pregnancy by qualitative PCR, quantitative PCR and immunohistochemistry. Expression of OT receptor and of the AVP receptors V1aR and V2R could be verified after sequencing the RT-PCR products of the expected length. The size of conceptuses used for quantitative PCR significantly increased with day of pregnancy (P<0.01) as did their quantitative expression of OTR (P<0.01). Immunohistochemistry of OTR resulted in weak trophectodermal abundance on Day 10, increasing at Day 12. On Day 14, staining intensity increased in individual cells of the trophectoderm while it decreased in other cells; this trend became more apparent on Day 16. The endoderm of the trophoblast and surrounding subtrophoblastic compartments always showed moderate staining for OTR. On Day 10 immunoreactive V2R protein was localised in the trophectodermal apical membrane; on Day 12 it was also present in the basal membrane and weakly in the cytoplasm. On Day 14 only individual trophectodermal cells showed positive supranuclear cytoplasmic areas or V2R, whereas on Day 16 about one-third of the trophectodermal cells were stained entirely and intensely positive. These results suggest an involvement of OT and AVP action in the development and expansion of the early equine conceptus.


Curcumin Alleviates oxLDL Induced MMP-9 and EMMPRIN Expression through the Inhibition of NF-κB and MAPK Pathways in Macrophages.
Rupture of vulnerable atherosclerotic plaques is the leading cause of acute myocardial infarction (AMI) and unstable angina pectoris (UA). However, it still lacks an effective therapy to stabilize the vulnerable atherosclerotic plaques. Numerous reports have shown that upregulation of MMP-9 (matrix metalloproteinase-9) and EMMPRIN (extracellular matrix metalloproteinase inducer) in macrophages is involved in the progression and development of vulnerable plaques. Here we evaluated the impact of curcumin on the expression of MMP-9 and EMMPRIN in macrophages. Macrophages were pretreated with curcumin or specific inhibitors (p38 MAPK inhibitor, NF-κB p65 inhibitor) for 1 h, then cells were cultured with oxLDL for indicated time. Real-time PCR and Western blot analysis were used to evaluate the expression of mRNA and proteins. Translocation of NF-κB p65 was detected by using laser confocal microscopy. Here we showed that curcumin attenuated the MMP-9 and EMMPRIN expression in oxLDL stimulated macrophages. Further studies revealed that curcumin inhibited oxLDL induced NF-κB activation and p38 MAPK phosphorylation. These findings illustrated that curcumin can inhibit the expression of EMMPRIN and MMP-9 in oxLDL stimulated macrophages through down regulation of NF-κB and p38 MAPK signaling pathways, which might be the molecular mechanism for the anti-atherosclerotic effect of curcumin.


Air pollution and associated respiratory morbidity in Delhi.
As a rapidly expanding centre of government, trade, commerce and industry, Delhi, the Indian capital, presents an instructive location for studying the possible association between air pollution and adverse health effects. This study tries to determine the association, if any, between the air pollutants--sulphur dioxide, nitrogen dioxide, carbon monoxide, ozone, suspended particulate matter and respiratory suspended particulate matter--and daily variations in respiratory morbidity in Delhi during the years 2004--2005. Data analysis was based on the Generalized Additive Poisson regression model including a Lowess smoothing function for the entire patient population and subgroups defined by season. The best fitting lag period for each pollutant was found by testing its concentration at varying lags. The model demonstrated associations between daily visits and some of the pollutants (O3, NO2 and RSPM) but their strongest components were observed at varying lags. A single pollutant model showed that a 10 microg m(-3) rise in pollutant level led to statistically significant relative risks (RR): 1.033 for O3, 1.004 for NO2, 1.006 for RSPM. The effect of particulate was relatively low, presumably because unlike other pollutants, particulate matter is not a single pollutant but rather a class of pollutants. This study, continued on a long term basis, can provide guidelines for anticipation/preparedness in the management of health care and hospital admissions.


Differential expression and network inferences through functional data modeling.
Time course microarray data consist of mRNA expression from a common set of genes collected at different time points. Such data are thought to reflect underlying biological processes developing over time. In this article, we propose a model that allows us to examine differential expression and gene network relationships using time course microarray data. We model each gene-expression profile as a random functional transformation of the scale, amplitude, and phase of a common curve. Inferences about the gene-specific amplitude parameters allow us to examine differential gene expression. Inferences about measures of functional similarity based on estimated time-transformation functions allow us to examine gene networks while accounting for features of the gene-expression profiles. We discuss applications to simulated data as well as to microarray data on prostate cancer progression.


[MRI analysis of the effect on mandibular retrusion with anterior disc displacement treated by using Herbst appliance].
Objective: To investgate the effect of Herbst appliance on the growth and remodeling of the temporomandibular joint (TMJ) in class Ⅱ patients with mandibular retrusion by using MRI. Methods: Between December 2010 and October 2014, 12 class Ⅱ patients (11-16 years old) with mandibular retrusion were chosen. The patients were divided into two groups. The control group included 7 patients (14 joints) with normal disc condyle relationship and the anterior disc displacement (ADD) group included 5 patients (10 joints) with anterior disc displacement. The MRI images of TMJ were measured, including condylar height, joint space index and disc position ratio, before and after the treatment. Results: The condylar height of the patients in the control group was significantly increased (P<0.001) after treatment, and no significant difference in joint space index (P=0.821) and disc position ratio (P=0.146) was found. The joint space index of the patients ([-14.70±8.82]% and [4.90±11.35]%) in ADD group changed significantly (P<0.001) after treatment, and no significant difference in condylar height (P=0.294) and disc position ratio (P=0.120) was found. Conclusions: The normal disc condyle relationship was beneficial to the reconstruction of the condylar process, and the increase of the condylar height. The condyle moved forward in patients with anterior disc displacement after treatment.


Downregulation of the CCAAT-enhancer binding protein beta in deltaFosB transgenic mice and by electroconvulsive seizures.
Previous studies demonstrate that chronic, but not acute electroconvulsive seizures (ECS), increases levels of deltaFosB, a long-lasting transcription factor, in the hippocampus, and this effect correlates with the slow onset and long-lasting clinical effects of antidepressant treatment. To understand how deltaFosB mediates long-term plasticity in the hippocampus, we analyzed the gene expression profile of inducible transgenic mice expressing deltaFosB with a highly sensitive microarray assay and a customized computer analysis program. The CCAAT-enhancing binding protein-beta (C/EBPbeta) was identified as one of the genes downregulated by deltaFosB in the hippocampus. The downregulation of C/EBPbeta in the inducible deltaFosB transgenic mice was confirmed by other quantitative assays including real-time RT-PCR and low density dot blotting. Analysis of the C/EBPbeta expression in the hippocampus of rats treated with ECS revealed that the C/EBPbeta mRNA was also downregulated by chronic, but not acute ECS administration, the most effective treatment for depression. Given the reported role of C/EBPbeta in behavioral conditioning models, it is possible that the deltaFosB-mediated downregulation of C/EBPbeta in the hippocampus may be a molecular mechanism by which antidepressants alleviate some of the symptoms of depressed patients.


[A study on digitally processed sounds designed to improve speech sound perception].
This study was performed to improve the speech sound perception of patients with sensorineural deafness by using digitally processed sounds. The fourteen CV sounds (/pa, ta, ka, ba, da, ga, ha, sa, za, ma, na, ra, ja, wa/) were selected in this study, and the consonant burst and/or voice onset time (VOT) of these sounds were doubled and/or amplified by digital processing and stored in DAT. These processed sounds and the original unprocessed sound were presented to patients and with moderate sensorineural deafness. The following results were obtained from patients who had made a mistake in discriminating the original sounds. 1. The correct answer rate for /ta/ and /sa/ was improved by amplification of the consonant burst or VOT, and for /ka/, amplification and/or repetition improved the corredt answer rate. Amplification of the consonant burst, or of the consonant burst with VOT, was especially effective for unvoiced explosive sounds (/pa, ta, ka/). 2. In voiced sounds, for /za/ and /ra/ the correct answer rate was improved by repetition or elongation of the consonant burst or transition part, and for /ga/, /ma/, and /na/ the rate was improved by amplification. 3. Semivowels (/wa, ja/) and glottal sounds (/ha/) were seldom misunderstood, and required no processing. Digital filtering processing was performed on monosyllables with the "s" sound (/sa, su, se, so/), and these filtered sounds were presented to the patients and a comparison was made with the original sounds. As a result, it was revealed that the correct answer rate could be improved by filtering, although the pass band was changed slightly by the succeeding vowel. This improvement was more apparent in the presence of environmental noise than under quiet conditions.


Use of ring-repeller, double-skimmer electrodes for efficient ion focusing in mass spectrometry.
The design and construction of a new type of time-of-flight mass spectrometer is described. The instrument was designed to improve the ionization efficiency and to efficiently detect ions. The system performance was evaluated using the SIMION software, and was compared with the experimental results. The shapes of the repeller, extraction, and ground electrodes had a strong effect on the trajectory of ions in the processes of ion acceleration and focusing. The major difference between the theory and the experiment can be attributed to space-charge effects.


Dual-Targeted Multifunctional Nanoparticles for Magnetic Resonance Imaging Guided Cancer Diagnosis and Therapy.
Hybrid nanostructures with combined functionalities can be rationally designed to achieve synergistic effects for efficient cancer treatment. Herein, a multifunctional nanoplatform is constructed, containing an inner core of an anticancer drug MTX surrounding by a nanometer-thin layer of gold as the shell with Fe3O4 magnetic nanoparticles (NPs) evenly distributed in the gold layer, and the outermost hybrid LA-PEG-MTX molecules as surface coating agent (denoted as MFG-LPM NPs). This nanocomposite possesses very high drug loading capacity as the entire core is MTX and integrates magnetic- and active- targeting drug delivery, light-controlled drug release, magnetic resonance imaging (MRI), as well as photothermal and chemotherapy. With a strong near-infrared (NIR) absorbance at 808 nm, the nanocomposite enables temperature elevation and light-triggered MTX release. In vitro cytotoxicity studies indicate that the strategy of combining therapy leads to a synergistic effect with high cancer cell killing efficacy. In consistency with this, due to the high accumulation of MFG-LPM NPs at tumor site and their combinatorial chemo-photothermal effects, 100% in vivo tumor elimination can be achieved. Additionally, in vivo MRI of tumor-bearing mice demonstrates an impressive performance of MFG-LPM NPs as a T2 contrast agent. Therefore, such multifunctional nanocomposite has the potential to serve as an excellent theranostic agent that collectively integrates multiple functions for efficient MRI guided cancer diagnosis and treatment.


Amaryllidaceae isocarbostyril alkaloids and their derivatives as promising antitumor agents.
This review covers the isolation, total synthesis, biologic activity, and more particularly the in vitro and in vivo antitumor activities of naturally occurring isocarbostyril alkaloids from the Amaryllidaceae family. Starting from these natural products, new derivatives have been synthesized to explore structure-activity relationships within the chemical class and to obtain potential candidates for preclinical development. This approach appears to be capable of providing novel promising anticancer agents.


Observation of broadband time-dependent Rabi shifting in microplasmas.
Coherent broadband radiation in the form of Rabi sidebands is observed when a ps probe laser propagates through a weakly ionized, electronically excited microplasma generated in the focus of an intense pump beam. The sidebands arise from the interaction of the probe beam with pairs of excited states of a constituent neutral atom via the probe-induced Rabi oscillation. Sideband shifting of >90 meV from the probe carrier frequency results in an effective bandwidth of 200 meV. The sidebands are controlled by the intensity and temporal profile of the probe pulse; with amplitude and shift in agreement with the predictions of a time-dependent generalized Rabi cycling model.


Impact of synthetic antioxidants on lipid peroxidation of distiller's dried grains with solubles and distiller's corn oil stored under high temperature and humidity conditions.
This experiment evaluated the effect of antioxidants, oil content in distiller's dried grains with solubles (DDGS), quality of distiller's corn oil, and storage time on lipid peroxidation. A source of low-oil DDGS (LO-DDGS; 5.0% ether extract [EE], as-fed basis), high-oil DDGS (HO-DDGS; 13.0% EE, as-fed basis), and 2 sources of distiller's corn oil (DCO; 1.20, 0.08, and 0.48% moisture, insoluble impurities, and unsaponifiables [MIU], respectively [DCO-1], and 1.20, 0.01, and 0.10% MIU, respectively [DCO-2]) were obtained. Each of the 4 ingredients was divided into 18 representative subsamples (approximately 908 g for DDGS or 2 kg of DCO). Six subsamples of each ingredient were mixed with either no supplemental antioxidants (CON), Rendox-CQ (REN; 1,000 mg/kg EE; Kemin, Industries, Des Moines, IA), or Santoquin-Q4T (SAN; 1,500 mg/kg EE; Novus International, St. Louis, MO). Each mixture ( = 72) was split into thirds, and 1 portion was immediately frozen at -20°C (d 0). Two portions were stored under hot (38.6 ± 0.1°C) and humid conditions (94.0 ± 0.3% relative humidity) for 14 or 28 d. The MIXED procedure of SAS was used to evaluate the effects of ingredient, antioxidant, storage time, and interactions, with d-0 values used as a covariate. From d 14 to 28, peroxide value (PV), -anisidine value (AnV), and thiobarbituric acid reactive substances (TBARS) of DCO and DDGS increased by 3- to 4-fold ( < 0.05). Over the entire storage period, PV of DCO-1 and HO-DDGS (12.3 ± 0.3 and 12.6 ± 0.3 mEq O/kg oil, respectively) exceeded ( < 0.05) that of DCO-2 and LO-DDGS (9.6 ± 0.3 and 9.3 ± 0.3 mEq O/kg oil, respectively). Adding REN or SAN ( < 0.05) reduced TBARS and AnV relative to CON (TBARS = 11.0 ± 0.2 mg malondialdehyde Eq/kg oil and AnV = 6.5 ± 0.2) over the entire period (mean of d 14 and 28), but TBARS and AnV did not differ ( > 0.05) between antioxidants (TBARS = 6.1 ± 0.2 and 5.9 ± 0.2 mg malondialdehyde Eq/kg oil, respectively, and AnV = 1.9 ± 0.2 and 1.8 ± 0.2 for REN and SAN, respectively). The PV on d 14 and 28 and overall was less ( < 0.05) when either antioxidant was added relative to CON (16.0 mEq O/kg) and was greater for ingredients treated with SAN ( < 0.05) compared with REN (8.8 ± 0.2 and 8.0 ± 0.2 mEq O/kg oil for SAN and REN, respectively). In summary, antioxidants reduced peroxidation of DDGS and DCO by approximately 50% during 28 d of storage at 38.6°C and 94.0% relative humidity, but neither antioxidant completely stabilized the ingredients.


INBREEDING AND FITNESS IN THE FRESHWATER SNAIL LYMNAEA PEREGRA: AN EVALUATION OVER TWO GENERATIONS OF SELF-FERTILIZATION.
Inbreeding depression was estimated from an outbreeding population of the freshwater snail Lymnaea peregra, on the basis of two successive generations of enforced selling and outcrossing, and 70 maternal lineages. Outcrossing was analyzed under two treatments, groups of two and five individuals. The fitness parameters measured included fecundity, growth, and survival. In the first generation, we contrasted three treatments (selfers vs. paired outcrossers and group outcrossers). Very similar results were obtained between the two outcrossing treatments. A strong self-fertilization depression (which includes parental fecundity and progeny fitness) was detected in the selling treatment (about 90%). In the second generation, there was again marked evidence for self-fertilization depression, with the highest contributions coming from parental fecundity and progeny hatching rate. Our results suggest that the decreased parental fecundity is a consequence of the mating system in the previous generation, although the role of partial self-incompatibility and the copulation behavior could not be ruled out. Hatching rate and early survival data are suggestive of purging of lethal mutations. Significant variation in fitness among selfing lineages was found for most fitness traits. Our experimental design also allowed to test for interactions among fitness loci. Only one trait of the nine studied behaved as expected under synergistic interactions. However we cannot rule out some purging during the experiment, which could have biased results towards linearity. Inbreeding depression was also inferred from the change of inbreeding level across generations in the same population. We obtained a value similar to the experimental estimate.


Treatment of Hodgkin's disease with MOPP chemotherapy: effect of dose and schedule modification on treatment outcome.
An analysis of the therapy details of 99 patients receiving primary MOPP chemotherapy for Hodgkin's disease revealed that treatment modification was a frequent occurrence. The mean cumulative dose calculated as a percentage of the projected ideal dose was 76%. Dose modifications of individual components of the MOPP combination were, however, variable and in part reflected disease-related factors, e.g. patients with stage 4 disease received significantly less vincristine than those with less advanced disease. An initial univariate analysis of factors influencing remission showed that the remission rate was significantly lower among those patients who had (a) liver involvement and (b) drug doses less than 75% of the ideal cumulative dose. Among the individual drug dosages, modification of the vincristine dose appeared to be the most significant treatment-related factor associated with lower remission rates. In a multivariate analysis where both disease-related and treatment-related factors were taken into account drug dosage remained a significant prognostic factor. The most important factors adversely affecting initial remission were the presence of liver involvement and reduction of the drug intensity index (cumulative dose divided by cumulative time). Disease-free survival was adversely influenced mainly by the presence of B symptoms and to a lesser degree, but still significantly, by a lower cumulative vincristine dose. Total survival was, however, influenced adversely only by the presence of B symptoms. The quality of MOPP therapy appears to play a significant role in determining the outcome of Hodgkin's disease.


Elevated anti-human T-cell lymphotropic virus type I antibody in serum of patients with retinal vasculitis and uveitis living in Izumo area.
Four patients with human T-lymphotropic virus type I associated myelopathy (HAM) were examined ophthalmologically, and serum titers to human T-lymphotropic virus type I (HTLV-I) in 11 patients with nonspecific retinal vasculitis or uveitis were determined. All of the patients lived in the Izumo area. All 4 patients with HAM (Cases 1 to 4) had vitreous opacities. Of the 11 patients with nonspecific retinal vasculitis or uveitis, 3 (Cases 5 to 7) had elevated titers to HTLV-I. We believe that HTLV-I infection may be involved in the causes of retinal vasculitis and uveitis in patients living not only in the endemic area but also outside the endemic area.


Crystallographic analysis of human serum albumin complexed with 4Z,15E-bilirubin-IXalpha.
Bilirubin, an insoluble yellow-orange pigment derived from heme catabolism, accumulates to toxic levels in individuals with impaired or immature liver function. The resulting jaundice may be managed with phototherapy to isomerize the biosynthetic 4Z,15Z-bilirubin-IXalpha to more soluble and excretable isomers, such as 4Z,15E-bilirubin. Bilirubin and its configurational isomers are transported to the liver by human serum albumin (HSA) but their precise binding location(s) on the protein have yet to be determined. To investigate the molecular details of their interaction, we co-crystallised bilirubin with HSA. Strikingly, the crystal structure--determined to 2.42 A resolution--revealed the 4Z,15E-bilirubin-IXalpha isomer bound to an L-shaped pocket in sub-domain IB. We also determined the co-crystal structure of HSA complexed with fusidic acid, an antibiotic that competitively displaces bilirubin from the protein, and showed that it binds to the same pocket. These results provide the first crystal structure of a natural bilirubin pigment bound to serum albumin, challenge some of the present conceptions about HSA-bilirubin interactions, and provide a sound structural framework for finally resolving the long-standing question of where 4Z,15Z-bilirubin-IXalpha binds to the protein.


Single nucleotide variant profiles of viable single circulating tumour cells reveal CTC behaviours in breast cancer.
Circulating tumour cell (CTC) behaviours are distinct from those of bulk tissues. Thus, treatments to eliminate CTCs differ from the regimens followed to reduce the primary tumour and its metastases. Accordingly, comprehensively deciphering the single nucleotide variant (SNV) profiles in CTCs, which partially determine CTC behaviours, is a priority. Using viable CTCs isolated with the oHSV1‑hTERT‑GFP virus coupled with fluorescence‑activated cell sorting (FACS), the whole genome was amplified using the multiple annealing and looping‑based amplification cycle (MALBAC) method. CTC behaviours were evaluated using the SNVs found to be recurrently mutated in different cells (termed CTC‑shared SNVs). Analysis of the sequencing data of 11 CTCs from 8 patients demonstrated that SNVs accumulated sporadically among CTCs and their matched primary tumours (22 co‑occurring mutated genes were identified in the exomes of CTCs and their matched primary tissues and metastases), and 394 SNVs were shared by at least two CTCs. Mutated APC and LRP1B genes co‑occurred in CTC‑shared and bulk‑tissue SNVs. Additionally, the breast‑originating identity of the CTC‑shared SNVs was verified, and they demonstrated the following CTC behaviours: i) intravasation competency; ii) increased migration or motility; iii) enhanced cell‑cell interactions; iv) variation in energy metabolism; v) an activated platelet or coagulation system; and vi) dysfunctional mitosis. These results demonstrated that it is feasible to capture and amplify the genomes of single CTCs using the described pipeline. CTC‑shared SNVs are a potential signature for identifying the origin of the primary tumour in a liquid biopsy. Furthermore, CTCs demonstrated some behaviours that are unique from those of bulk tissues. Therefore, therapies to eradicate these precursors of metastasis may differ from the existing traditional regimens.


The progression of cell death affects the rejection of allogeneic tumors in immune-competent mice - implications for cancer therapy.
Large amounts of dead and dying cells are produced during cancer therapy and allograft rejection. Depending on the death pathway and stimuli involved, dying cells exhibit diverse features, resulting in defined physiological consequences for the host. It is not fully understood how dying and dead cells modulate the immune response of the host. To address this problem, different death stimuli were studied in B16F10 melanoma cells by regulated inducible transgene expression of the pro-apoptotic active forms of caspase-3 (revCasp-3), Bid (tBid), and the Mycobacterium tuberculosis-necrosis inducing toxin (CpnTCTD). The immune outcome elicited for each death stimulus was assessed by evaluating the allograft rejection of melanoma tumors implanted subcutaneously in BALB/c mice immunized with dying cells. Expression of all proteins efficiently killed cells in vitro (>90%) and displayed distinctive morphological and physiological features as assessed by multiparametric flow cytometry analysis. BALB/c mice immunized with allogeneic dying melanoma cells expressing revCasp-3 or CpnTCTD showed strong rejection of the allogeneic challenge. In contrast, mice immunized with cells dying either after expression of tBid or irradiation with UVB did not, suggesting an immunologically silent cell death. Surprisingly, immunogenic cell death induced by expression of revCasp-3 or CpnTCTD correlated with elevated intracellular reactive oxygen species (ROS) levels at the time point of immunization. Conversely, early mitochondrial dysfunction induced by tBid expression or UVB irradiation accounted for the absence of intracellular ROS accumulation at the time point of immunization. Although ROS inhibition in vitro was not sufficient to abrogate the immunogenicity in our allo-immunization model, we suggest that the point of ROS generation and its intracellular accumulation may be an important factor for its role as damage associated molecular pattern in the development of allogeneic responses.


The need for risk factor assessment in atherothrombotic vascular disease.
Risk factors for cardiovascular disease are characteristically associated with an increased likelihood of disease. Prospective studies of incident disease are less prone to bias than cross-sectional or case-control studies of prevalent disease. Meta-analyses of prospective studies provide more reliable estimates of the strength of association of risk factors with risk of disease than individual studies. Meta-analyses of intervention studies provide the most reliable estimates of reversibility of disease risk through prolonged reduction of classical risk factors (e.g., blood pressure, serum cholesterol). Emerging potential risk factors include markers of infection, inflammation, and thrombosis; their possible roles in causation and in risk prediction require much further study.


Involvement of DPPIV/CD26 in epithelial morphology and suppressed invasive ability in ovarian carcinoma cells.
Dipeptidyl peptidase IV (DPPIV) is a multifunctional cell surface aminopeptidase with ubiquitous expression and it has a variety of functional properties in the development of human malignancies. In the present study, we showed the possible correlation between DPPIV/CD26 expression and less migratory potential with decreased MMP-2 expression in ovarian carcinoma cells. Moreover, induction of DPPIV/CD26 resulted in reduced expressions of MMP-2 and mesenchymal markers such as vimentin and SMA, with a less invasive potential and an epithelial morphologic change. This evidence implies that DPPIV/CD26 may play a crucial role in the antimetastatic potential in ovarian carcinoma.


Mechanism for complement-mediated, antibody-dependent enhancement of human immunodeficiency virus type 1 infection in MT2 cells is enhanced entry through CD4, CD21, and CXCR4 chemokine receptors.
Some antibodies neutralize Human Immunodeficiency Virus (HIV). However, antibody to HIV and complement can enhance HIV replication if cells express both complement receptors and CD4, a phenomenon described as complement-mediated, antibody-dependent enhancement (C'ADE). Although increased binding of opsonized virions has been reported, the mechanism by which C'ADE enhances HIV replication remains unproven. In this study, real-time polymerase chain reaction to detect HIV cDNA indicates that complement and anti-HIV antibodies enhance HIV entry 8- to 30- fold with similar increases in integrated provirus. Thus, complement increases HIV replication through a mechanism of enhanced entry. To further refine the mechanism of C'ADE, chemokine receptor antagonists were employed. JM2987, a CXCR4 chemokine receptor antagonist, blocked HIV infection and C'ADE; thus CD4, complement receptors, and CXCR4 chemokine receptors are required for enhanced entry of HIV into MT2 cells. Finally, anti-HIV immunoglobulin enhanced replication of not only group M clade B HIV but also group M clade D and group O isolates. These data demonstrate that antibodies mediating C'ADE of HIV infection are broadly reactive.


Surgical management of radiation-induced heart disease.
With the increasing population of patients with prior mediastinal irradiation, cardiac surgeons will encounter patients with radiation-induced damage to the heart and the great vessels. Awareness of the pathology and the surgical management is essential to provide optimal care for these patients. Eight patients with radiation-induced heart disease were encountered in the last 10 years. After a brief clinical presentation, the surgical management of radiation-induced heart disease is reviewed. Radiation can affect all the structures in the heart, including the coronary arteries, the valves, and the conduction system. The pericardium is the most commonly involved, and the conduction system is the least involved. Pericardiectomy is quite effective in patients with symptomatic pericardial effusion or constriction. The coronary lesions are located predominantly in the ostial or proximal regions of the epicardial vessels. Percutaneous transluminal coronary angioplasty alone appears to have a high rate of restenosis. Surgical revascularization has good long-term results, and the internal mammary artery should be used if it is satisfactory. The aortic and mitral valves are more commonly involved than the tricuspid and pulmonary valves. Myocardial dysfunction predominantly affects the right ventricle and requires particular attention during cardiopulmonary bypass and in the postoperative period. Restoration of sinus rhythm is essential in view of stiffness of the ventricles. Flexibility in the surgical approach with selective use of thoracotomy will facilitate the surgical procedure in certain patients. Surgeons should be well versed in all the manifestations and the management of radiation-induced heart disease.


The effect of losartan and carvedilol on vasopressor responses to adrenergic agonists and angiotensin II in the systemic circulation of Sprague Dawley rats.
1 Interaction between renin-angiotensin (RAS) and sympathetic nervous systems (SNS) was investigated by examining the effect of cumulative blockade of angiotensin II (Ang II) and adrenergic receptors in normal Sprague Dawley rats. 2 Rats were treated with losartan (10 mg/kg), carvedilol (5 mg/kg), or losartan plus carvedilol (10+5 mg/kg) orally for 7 days. On day 8, the animals were anaesthetized with pentobarbitone and prepared for systemic haemodynamic study. Dose-response relationships for the elevation of mean arterial pressure or change in heart rate (HR) in response to intravenous injections of noradrenaline (NA), phenylephrine (PE), methoxamine (ME) and Ang II were determined. 3 Losartan or the combination of losartan with carvedilol blunted vasopressor responses to ME and Ang II. Dose-response relationships for agonist action on HR were significantly inhibited by all treatments except for the combination of losartan and carvedilol on the decrease in HR induced by PE. Carvedilol decreased vasopressor responses to NA, PE and Ang II, and HR responses to NA, ME and Ang II. Combination treatment produced similar effects to losartan on the vasopressor and HR responses but had a greater effect on vasopressor responses to ME and Ang II, and on HR responses to NA and Ang II than carvedilol alone. 4 It is concluded that peripheral vasoconstriction induced by Ang II is partly mediated by adrenergic action and that the vasopressor responses to adrenergic agonists depend on an intact RAS. These observations suggest an interactive relationship between RAS and SNS in determining systemic haemodynamic responses in 'normal' rats.


Neoadjuvant therapy with sorafenib in advanced renal cell carcinoma with vena cava extension submitted to radical nephrectomy.
A 71-year-old man with advanced left renal cell carcinoma (lymph node involvement and vena cava thrombus) was submitted to 6 months of neoadjuvant treatment with sorafenib before open radical nephrectomy. After sorafenib treatment and before surgery a new CT scan confirmed the presence of a 9.0 cm in diameter solid mass in the left kidney but a reduction in thrombus extension, limited to the left renal vein. At histological examination after radical nephrectomy, over 90% of the renal mass was substituted by necrotic tissue.


Epidural blood patch for spontaneous intracranial hypotension (SIH): a report of two cases.
One of the latest diagnoses that need to be considered when evaluating patients with persistent headache is spontaneous (postural) intracranial hypotension (SIH). The diagnosis can be clinched by magnetic resonance imaging (MRI) findings of subdural collections, meningeal enhancement and tonsillar descent. Cerebrospinal fluid leak has been postulated as the cause, and both medical and surgical treatment options have been documented. The treatment of choice is, however, an epidural blood patch. Here we discuss two cases of SIH treated successfully with epidural blood patch.


Effectiveness of taping and bracing in balance.
Taping and bracing are thought to be effective methods in restricting the ankle's joint motion and assisting prevention of injuries. Research evidence suggests that taping and bracing enhance both the mechanical support and the proprioception of the ankle. However, there is little research concerning the influence of taping and bracing on sport performance. Research has mainly examined tasks with demands on the frontal plane. Therefore, the present study examined the effect of taping and bracing on the performance of a task with demands on the frontal plane. A sample of 30 physical education students (Mage=21.9 yr.) performed a balance task requiring estimation of balance and both right and left deviations. The subjects performed the balance task on four different conditions, with tape, with Swede-O (a lace-up, boot style stabilizer), with Aircast (an inflatable cast), and without any stabilizer. There were no significant differences among the conditions. These findings indicate that taping and bracing do not have negative effects on balance in the frontal plane. This study created concerns regarding the appropriate stabilizer for different tasks, bilateral coordination after the application of a stabilizer, and the influence of psychological factors on prevention of injury.


SIRT1 regulates the phosphorylation and degradation of P27 by deacetylating CDK2 to promote T-cell acute lymphoblastic leukemia progression.
Despite marked advances in the clinical therapies, clinical outcome of most T-cell acute lymphoblastic leukemia (T-ALL) patients remains poor, due to the high risk of relapse, even after complete remission. Previous studies suggest that the NAD-dependent deacetylase sirtuin 1 (SIRT1) has a dual role in hematologic malignancies, acting as a tumor suppressor or tumor promoter depending on the tumor type. However, little is known about the expression and functions of SIRT1 in T-ALL leukemogenesis. Public RNA-seq data, a Notch1 driven T-ALL mouse model and γ-secretase inhibitor were used to identify SIRT1 expression in T-ALL. We knocked down SIRT1 expression with ShRNAs and assessed the impacts of SIRT1 deficiency on cell proliferation, colony formation, the cell cycle and apoptosis. Transgenic SIRT1 knockout mice were used to determine the function of SIRT1 in vivo. RT-PCR, western blot, co-immunoprecipitation and ubiquitination analyses were used to detect SIRT1, p27 and CDK2 expression and their interactions. SIRT1 protein expression was positively correlated with the activation of Notch1. Downregulation of SIRT1 expression suppressed the proliferation and colony formation of T-ALL cell lines, which was reversed by SIRT1 overexpression. SIRT1 silencing prolonged the lifespan of T-ALL model mice. We demonstrated that p27 was involved in the downstream mechanism of cell cycle arrest induced by silencing SIRT1. SIRT1 increased the phosphorylation of p27 on Thr187 by deacetylating CDK2 and enhanced the interaction between p27 and SKP2 leading to the degradation of p27. Our findings suggest that SIRT1 is a promising target in T-ALL and offer a mechanistic link between the upregulation of SIRT1 and downregulation of p27.


Safety and tolerability of dexmecamylamine (TC-5214) adjunct to ongoing antidepressant therapy in patients with major depressive disorder and an inadequate response to antidepressant therapy: results of a long-term study.
Safety and tolerability are important considerations when selecting patients' treatment for major depressive disorder. We report the long-term safety and tolerability of the nicotinic channel modulator dexmecamylamine (TC-5214), adjunct to selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) in patients with major depressive disorder and who had an inadequate response to antidepressants. This 52-week, double-blind, placebo-controlled study explored the long-term safety and tolerability of dexmecamylamine. Patients were randomized 3:1 to receive flexibly dosed dexmecamylamine 1 to 4 mg adjunct to SSRI/SNRI or placebo plus SSRI/SNRI. The patient population comprised inadequate responders from 2 Phase III acute dexmecamylamine studies (NCT01157078 [study 002], NCT01153347 [study 004]) and de novo patients who responded inadequately during a 6-week open-label antidepressant treatment period preceding randomization. Safety and tolerability were assessed by monitoring adverse events, vital signs, and physical and laboratory parameters. Descriptive statistical analyses were performed on most efficacy-related end points. Sustained efficacy was analyzed using logistic regression. Overall, 813 patients were randomized (610 received dexmecamylamine, 203 received placebo). In total, 82.4% and 84.6% of patients, respectively, experienced an adverse event. Adverse events occurring more frequently with dexmecamylamine vs placebo were constipation (19.6% vs 6.0%), dizziness (12.0% vs 7.0%), and dry mouth (9.7% vs 5.0%). Back pain (2.8% vs 8.5%), weight increase (4.4% vs 7.0%), and fatigue (5.6 % vs 7.5%) occurred more frequently in placebo-treated patients. No notable differences were observed between dexmecamylamine and placebo for any secondary end point. In this long-term study, safety and tolerability of dexmecamylamine were consistent with that reported in acute Phase III studies of dexmecamylamine.


Sauvé-Kapandji and reverse Sauvé-Kapandji procedures for treating chronic longitudinal radioulnar dissociation with capitellum fracture.
Almost all reported cases of longitudinal radioulnar dissociation have involved fracture of the radial head, rupture of the interosseous membrane, and disruption of the distal radioulnar joint, although unusual patterns of Essex-Lopresti injury have also been described. To our knowledge, this is the first report of a chronic Essex-Lopresti variant including fracture of the capitellum. A displaced capitellum fracture must alert to the possibility of longitudinal radioulnar dissociation, even without concomitant radial head fracture or symptoms at the forearm and ulnar wrist. Successful mid-term results can be achieved by treating malunion of humeral condyle and proximal migration of the radius with simultaneous Sauvé-Kapandji procedure at the wrist and reverse Sauvé-Kapandji at the elbow.


The effect of pH adjustment of bupivacaine on onset and duration of epidural anaesthesia for caesarean section.
Previous studies have reported that elevation of the pH of local anaesthetics results in more rapid onset of action, with enhanced quality and duration of block. This study investigated the effect of pH adjustment of 0.5 per cent bupivacaine immediately prior to epidural anaesthesia for Caesarean section. Addition of 0.1 ml of 8.4 per cent sodium bicarbonate to 20 ml of 0.5 per cent bupivacaine consistently raised the pH of the local anaesthetic from 5.49 to 7.04 (mean values). One hundred patients, presenting for elective Caesarean section under epidural anaesthesia participated in the study. Forty patients received epidural anaesthesia, using pH-adjusted 0.5 per cent bupivacaine, in a dosage adequate to produce block to the T4 level. A control group of 40 patients received the standard commercial preparation of 0.5 per cent bupivacaine. A further ten patients in each group received epidural anaesthesia using 0.5 per cent bupivacaine with the addition of 1:400,000 epinephrine, to study the effect of epinephrine on pH adjustment of the local anaesthetic. Elevation of the pH of the local anaesthetic significantly increased the speed of onset of action from 6.4 minutes to 3.2 minutes and the time to peak effect from 24.8 minutes to 18.1 minutes, while the duration of anaesthesia was increased from 124.8 minutes to 147.3 minutes. The time to S2 segment blockade was also shortened from 13.5 to 8.6 minutes. Addition of 1:400,000 epinephrine to the local anaesthetic did not influence the effect of pH adjustment. Maternal and umbilical cord plasma levels of bupivacaine were not affected by pH adjustment of the local anaesthetic, while MV/UV and UA/UV ratios were unaltered.


Ebselen: a new approach to the inhibition of peroxide-dependent inflammation.
Ebselen is a novel organo-selenium compound which catalytically inactivates peroxides in vitro in a manner similar to that of glutathione peroxidase (GSH-Px). In addition, ebselen also inactivates leukotriene B4 (LTB4) generated by pig leukocytes in vitro by isomerizing this eicosanoid to its biologically inactive 6-trans isomer. In vivo, ebselen is a weak oral inhibitor of carrageenan paw oedema and adjuvant arthritis in the rat, differentiating it from classical NSAIDs such as indomethacin and diclofenac. In contrast, oral ebselen, like (intra-articular) catalase, is an effective inhibitor of monoarthritis induced in mice with amidated glucose oxidase (aGO) and dose-dependently inhibits cobra-venom-factor-induced paw oedema in rats. Indomethacin and piroxicam are weakly active or ineffective in these models. The data indicate that ebselen is likely to be useful in the therapy of inflammatory conditions in which reactive oxygen species, such as peroxides, play an aetiological role.


Development of models and theories on the concept of nursing.
This paper shows how models can be used by practitioners of nursing as a practical tool to analyse their own practice, in particular to assess needs and to plan, implement, and evaluate care. It is argued that the impact of existing work in theory development has been relatively small, at least in the UK, because the theories are not sufficiently specific to everyday nursing activities and the models are over elaborate and not universally applicable. A simple model of nursing, based on a systems approach is presented and applied to one particular field of nursing practice, i.e. health visiting. The model, which can be used in any field of nursing, stresses the reciprocity of the nurse-patient relationship, and the significance of the environment in determining the concepts of nurse, patient and nursing.


Plant Promoter Analysis: Identification and Characterization of Root Nodule Specific Promoter in the Common Bean.
The upstream sequences of gene coding sequences are termed as promoter sequences. Studying the expression patterns of promoters are very significant in understanding the gene regulation and spatiotemporal expression patterns of target genes. On the other hand, it is also critical to establish promoter evaluation tools and genetic transformation techniques that are fast, efficient, and reproducible. In this study, we investigated the spatiotemporal expression pattern of the rhizobial symbiosis-specific nodule inception (NIN) promoter of Phaseolus vulgaris in the transgenic hairy roots. Using plant genome databases and analysis tools we identified, isolated, and cloned the P. vulgaris NIN promoter in a transcriptional fusion to the chimeric reporter β-glucuronidase (GUS) GUS-enhanced::GFP. Further, this protocol describes a rapid and versatile system of genetic transformation in the P. vulgaris using Agrobacterium rhizogenes induced hairy roots. This system generates ≥2 cm hairy roots at 10 to 12 days after transformation. Next, we assessed the spatiotemporal expression of NIN promoter in Rhizobium inoculated hairy roots at periodic intervals of post-inoculation. Our results depicted by GUS activity show that the NIN promoter was active during the process of nodulation. Together, the present protocol demonstrates how to identify, isolate, clone, and characterize a plant promoter in the common bean hairy roots. Moreover, this protocol is easy to use in non-specialized laboratories.


Conflict adaptation: it is not what you expect.
In two studies, a vocal Stroop task with eight different colours was employed in order to put two core assumptions of the original interpretation of the Gratton effect to the test. We verified whether top-down control processes can elicit conflict adaptation when episodic memory effects are controlled for and to what extent proactive adjustments driven by the subjects' expectancy for congruency level repetition contribute to this effect. Therefore, we presented Stroop stimuli without feature repetitions and investigated whether the induced expectancy manipulation of raising the amount of either congruency level repetitions or alternations in a training phase transferred to an unmanipulated test phase. Over the two experiments, a sequential modulation of the Stroop effect was found in the absence of stimulus feature repetitions, strongly confirming a share for top-down control processes in bringing about the Gratton effect. In the condition where congruency level repetitions were raised, a strong Gratton effect was found. When congruency level alternations outnumbered repetitions, the Gratton effect disappeared completely. However, this difference seemed mainly due to cumulative effects of local, dynamic, trial-to-trial control adjustments rather than expectancy-induced attentional shifting. Once the transition probability changed back to 50% in the test phase of each experiment, a similar Gratton effect was found in both conditions. Taken together, these results are best explained in terms of dynamic reactive control.


Analysis of interdigital spaces during mouse limb development at intervals following amniotic sac puncture.
A spectrum of limb abnormalities ranging from adactyly, syndactyly, acrosyndactyly to nail hypoplasia was encountered in mouse embryos subjected to amniotic sac puncture at the corresponding gestational stage when human chorionic villus sampling (cvs) would normally be performed clinically. Previous skeletal studies revealed that, apart from the occasional incidence of fusion of 2 distal phalanges, syndactyly usually only affected the soft tissues within the interdigital spaces. A similar situation was also observed in cases of adactyly; while the skeletal elements of the digits were present, the soft tissues in the interdigital spaces failed to separate. A transient period of bradycardia is induced, possibly secondary to compression of the embryo by the extraembryonic membranes and uterine muscles following amniotic sac puncture. These factors, we believe, produce temporary hypoxia/ischaemia of the distal extremities, and may lead to the modification of the interdigital mesenchymal tissues within the autopods. In order to investigate the mechanism(s) underlying soft tissue syndactyly, limbs recovered at 0.5, 4, 8, 12, 24, or 36 h following amniotic sac puncture (ASP) were examined histologically. Vascular disruption in the form of localised areas of haemorrhage, vascular dilatation and congestion and the presence of fluid-filled cavities occurred in relation to the marginal vein and vascular plexus in the interdigital spaces. It is hypothesised that this interfered with the normal equilibrium of the preset programs of mitosis/cell death and apoptosis within the mesenchymal cells of the interdigital spaces. Apoptosis in these areas was inhibited in the majority of the experimental limbs analysed 4 h after ASP. Instead of undergoing necrosis/apoptosis, increased mitotic activity was usually observed from 8 h following ASP at the sites where apoptosis would normally be expected to be seen. The aberrant fate of the interdigital mesenchyme following ASP and the underlying mechanism(s) involved are discussed, as is the critical importance of an adequate vascular supply to the interdigital spaces during the morphogenesis of the autopod. We believe that this report contributes to understanding the mechanism(s) which lead to syndactyly following ASP, and the limb defects occasionally seen following cvs when this is undertaken during early gestation.


Paint-thinner-induced Acute Kidney Injury: A Case Series and Review.
Occupational health hazards contribute significantly to the morbidity and mortality of workers in factories. Toluene has become a widely abused inhaled volatile drug. The spectrum of toluene-induced renal injury includes rhabdomyolysis, myoglobinemia, distal renal tubular acidosis (RTA), acute tubular necrosis, glomerulonephritis, and interstitial nephritis. We describe two patients with paint-thinner-induced kidney injury who were affected through different routes of exposure and recovered well, with one requiring dialysis support; the second patient, who had developed Type 1 distal RTA and mild kidney injury, was managed with conservative measures. Toluene can cause acute neurological symptoms, accompanied by severe metabolic alterations, as well as organ injury and dysfunction. A common association of the development of hypokalemic paralysis and metabolic acidosis with toluene intoxication was observed. Liver injury and rhabdomyolysis are also common. Vomiting, dehydration, tubular injury, and rhabdomyolysis are all possible additional causes of acute renal failure in toluene intoxication. Type 1 distal RTA, which is characterized by an inability to lower urine pH despite acidemia, results in hyperchloremic metabolic acidosis with hypokalemia. The management of acute toluene toxicity is largely conservative, consisting of correcting the electrolytes and the acid-base balance, fluid alterations, and renal replacement therapy in severe acute kidney injury. A clinical suspicion of organ failure and prompt supportive care leads to encouraging results. Adequate protective steps for workplaces involved in the use of such substances in confined spaces include prior risk assessment, using low-toxicity chemical products, ensuring adequate ventilation, safety training, and using appropriate personal protective equipment.


Autologous platelet-rich plasma infusion improves clinical pregnancy rate in frozen embryo transfer cycles for women with thin endometrium.
Adequate thickness of the endometrium has been well recognized as a critical factor for embryo implantation. This was a prospective cohort study to investigate the benefits of platelet-rich plasma (PRP) for women with thin endometrium who received frozen embryo transfer (FET) program in a larger number of patients and explore the underlying mechanism. In this study, we investigated the effects of PRP in women with thin endometrium in FET program. 64 patients with thin endometrium (<7 mm) were recruited. PRP intrauterine infusion was given in PRP group during hormone replacement therapy (HRT) cycle in FET cycles. After PRP infusion, the endometrium thickness in PRP group was 7.65 ± 0.22 mm, which was significantly thicker than that in control group (6.52 ± 0.31 mm) (P <.05). Furthermore, PRP group had lower cycle cancellation rate when compared to control group (19.05% vs. 41.18%, P <.01). The implantation rate and clinical pregnancy rate in PRP group were significantly higher than those in control group (27.94% vs 11.67%, P <.05; 44.12% vs 20%, P <.05, respectively). PRP blood contained 4 folds higher platelets and significantly greater amounts of growth factors including platelet-derived growth factor (PDGF)-AB, PDGF-BB, and transforming growth factor (TGF)-β than peripheral blood (P <.01). PRP plays a positive role in promoting endometrium proliferation, improving embryo implantation rate and clinical pregnancy rate for women with thin endometrium in FET cycles.


A matrix formalism for decentration problems.
A matrix approach to decentration problems is presented which reduces the common decentration problems of ophthalmic optics to simple matrix multiplications. The formalism also leads to an alternative derivation of Thomson's formulas for obliquely crossed spherocylindrical lenses.


Graded replacement of maize grain with molassed sugar beet pulp modulated ruminal microbial community and fermentation profile in vitro.
Molassed sugar beet pulp (Bp) is a viable alternative to grains in cattle nutrition for reducing human edible energy input. Yet little is known about the effects of high inclusion rates of Bp on rumen microbiota. This study used an in vitro approach and the quantitative polymerase chain reaction technique to establish the effects of a graded replacement of maize grain (MG) by Bp on the ruminal microbial community, fermentation profile and nutrient degradation. Six different amounts of Bp (0-400 g kg-1 ), which replaced MG in the diet, were tested using the in vitro semi-continuous rumen simulation technique. The increased inclusion of Bp resulted in greater dietary content and degradation of neutral detergent fibre (P < 0.01). Further, Bp feeding enhanced (P < 0.01) the abundance of genus Prevotella and shifted (P < 0.01) the short-chain fatty acid patterns in favour of acetate and propionate and at the expense of butyrate. A total replacement of MG with Bp resulted in an increased daily methane production (P < 0.01). Results suggest positive effects of the replacement of MG by Bp especially in terms of stimulating ruminal acetate and propionate fermentation. However, high replacement rates of Bp resulted in lowered utilization of ammonia and higher ruminal methane production. © 2017 Society of Chemical Industry.


Neurocognitive deficits are relevant for the jumping-to-conclusions bias, but not for delusions: A longitudinal study.
Patients with delusions exhibit an increased tendency to arrive at decisions based on very limited evidence (jumping-to-conclusions; JTC), making this reasoning bias relevant for the treatment of delusions. Neurocognitive deficits contribute to JTC, but it is not known whether this has any bearing on the clinical syndrome of delusions. We addressed this question by reanalyzing data from an efficacy study of non-pharmacological interventions as adjunctive treatments in schizophrenia. We investigated the longitudinal associations of cognitive functioning, JTC and delusions in patients with psychotic disorders receiving either a metacognitive intervention addressing reasoning biases (n = 59), or cognitive remediation (n = 58). Both interventions improved JTC; in the cognitive remediation group, tentative evidence suggested that better neurocognitive performance contributed to this improvement. However, JTC gains were associated with delusion improvement only in the metacognitive intervention group, suggesting a content-specific mechanism of action.


A Flexible, Practical, and Stereoselective Synthesis of Enantiomerically Pure trans-5-Oxohexahydropyrrolo[3,2-b]pyrroles (Pyrrolidine-trans-lactams), a New Class of Serine Protease Inhibitors, Using Acyliminium Methodology.
A flexible, practical, and stereoselective synthesis of enantiomerically pure trans-5-oxohexahydropyrrolo[3,2-b]pyrroles (pyrrolidine-trans-lactams) is described. The key reaction involves addition of Z-ketene acetal 24 to the acyliminium ion derived from 48. This reaction is mediated by BF3·OEt2 and introduces the 6S and 6aS stereocenters stereoselectively. The acyliminium precursor was prepared in four different ways: from racemic 2,4-diaminobutyric acid 8, from (R)-asparagine, from (R)-methionine, and via a crystallization-induced dynamic resolution of a salt of the racemic amine 56. (R)-Methionine is the preferred starting material for the preparation of enantiomerically pure material. The best conditions for addition of the ketene acetal to the acyliminium ion derived from 48 were determined by systematically screening a range of ketene acetals and Lewis acids. The best ketene acetal was Z-(1-ethoxy-3-methylbut-1-enyloxyl)triisopropylsilane 24. In this series, the bulk of the silyl group of the Z-ketene acetal can be correlated with increased 6S isopropyl product. Use of the E-ketene acetal does not lead to a significant change in stereoselectivity for the 6R isopropyl product. In contrast, variation of the Lewis acid has a considerable effect on the product stereochemistry. While BF3·OEt2 gives predominantly 6S,6aS product, AlCl3 and TiCl4 give predominantly mixtures of the 6R,6aS and 6S,6aS products and TMSOTf gives 6aR material with predominantly one unknown isopropyl isomer (trans-lactam numberings used). The synthesis can conveniently be carried out on a large scale to produce multigram quantities of the trans-lactam 28, which is a key precursor of pharmacologically active molecules such as 1, a selective and orally active human neutrophil elastase inhibitor. The overall chemical yield of 1 is 1.3%, corresponding to an average of >70% yield for each of the 14 steps, and the synthesis contains only one chromatographic purification.


Predictive models for estimating visceral fat: The contribution from anthropometric parameters.
Excessive adipose visceral tissue (AVT) represents an independent risk factor for cardiometabolic alterations. The search continues for a highly valid marker for estimating visceral adiposity that is a simple and low cost tool able to screen individuals who are highly at risk of being viscerally obese. The aim of this study was to develop a predictive model for estimating AVT volume using anthropometric parameters. Excessive adipose visceral tissue (AVT) represents an independent risk factor for cardiometabolic alterations. The search continues for a highly valid marker for estimating visceral adiposity that is a simple and low cost tool able to screen individuals who are highly at risk of being viscerally obese. The aim of this study was to develop a predictive model for estimating AVT volume using anthropometric parameters. A cross-sectional study involving overweight individuals whose AVT was evaluated (using computed tomography-CT), along with the following anthropometric parameters: body mass index (BMI), abdominal circumference (AC), waist-to-hip ratio (WHpR), waist-to-height ratio (WHtR), sagittal diameter (SD), conicity index (CI), neck circumference (NC), neck-to-thigh ratio (NTR), waist-to-thigh ratio (WTR), and body adiposity index (BAI). 109 individuals with an average age of 50.3±12.2 were evaluated. The predictive equation developed to estimate AVT in men was AVT = -1647.75 +2.43(AC) +594.74(WHpR) +883.40(CI) (R2 adjusted: 64.1%). For women, the model chosen was: AVT = -634.73 +1.49(Age) +8.34(SD) + 291.51(CI) + 6.92(NC) (R2 adjusted: 40.4%). The predictive ability of the equations developed in relation to AVT volume determined by CT was 66.9% and 46.2% for males and females, respectively (p<0.001). A quick and precise AVT estimate, especially for men, can be obtained using only AC, WHpR, and CI for men, and age, SD, CI, and NC for women. These equations can be used as a clinical and epidemiological tool for overweight individuals.


Prevalence and antimicrobial resistance profiles of Vibrio spp. and Enterococcus spp. in retail shrimp in Northern California.
Shrimp is one of the most consumed seafood products globally. Antimicrobial drugs play an integral role in disease mitigation in aquaculture settings, but their prevalent use raises public health concerns on the emergence and spread of antimicrobial resistant microorganisms. Vibrio spp., as the most common causative agents of seafood-borne infections in humans, and Enterococcus spp., as an indicator organism, are focal bacteria of interest for the monitoring of antimicrobial resistance (AMR) in seafood. In this study, 400 samples of retail shrimp were collected from randomly selected grocery stores in the Greater Sacramento, California, area between September 2019 and June 2020. The prevalence of Vibrio spp. and Enterococcus spp. was 60.25% (241/400) and 89.75% (359/400), respectively. Subsamples of Vibrio (n = 110) and Enterococcus (n = 110) isolates were subjected to antimicrobial susceptibility testing (AST). Vibrio isolates had high phenotypic resistance to ampicillin (52/110, 47.27%) and cefoxitin (39/110, 35.45%). Enterococcus were most frequently resistant to lincomycin (106/110, 96.36%), quinupristin-dalfopristin (96/110, 87.27%), ciprofloxacin (93/110, 84.55%), linezolid (86/110, 78.18%), and erythromycin (58/110, 52.73%). For both Vibrio and Enterococcus, no significant associations were observed between multidrug resistance (MDR, resistance to ≥3 drug classes) in isolates from farm raised and wild caught shrimp (p > 0.05) and in isolates of domestic and imported origin (p > 0.05). Whole genome sequencing (WGS) of a subset of Vibrio isolates (n = 42) speciated isolates as primarily V. metschnikovii (24/42; 57.14%) and V. parahaemolyticus (12/42; 28.57%), and detected 27 unique antimicrobial resistance genes (ARGs) across these isolates, most commonly qnrVC6 (19.05%, 8/42), dfrA31 (11.90%, 5/42), dfrA6 (9.5%, 4/42), qnrVC1 (9.5%, 4/42). Additionally, WGS predicted phenotypic resistance in Vibrio isolates with an overall sensitivity of 11.54% and specificity of 96.05%. This study provides insights on the prevalence and distribution of AMR in Vibrio spp. and Enterococcus spp. from retail shrimp in California which are important for food safety and public health and exemplifies the value of surveillance in monitoring the spread of AMR and its genetic determinants.


Waste lime as a potential cation source in the phosphate crystallization process.
In this study, the feasibility of waste lime as a potential cation source in phosphate crystallization process was investigated using laboratory scale up flow reactors, adopting sequencing batch type configuration. This research focused on its successful application in a novel sludge treatment process, which is comprised of a high performance fermenter (operating conditions: 55 degree C and pH 9) followed by a crystallization reactor. In the struvite precipitation test using synthetic wastewater, considerable nutrient removal (about 60%) in the form of ammonia and phosphate was observed within 0.5-1 hr of retention time, and only small amounts (< 5%) of ammonia stripping occurred naturally due to the alkaline (pH 9) characteristic of the feed substrate. By replacing the synthetic wastewater with the fermentation effluent, the optimal dosage of magnesium salt for struvite precipitation was 0.86 g Mg g(-1) P, similar to the mass ratio of the struvite. The optimal dosage of waste lime was 0.3 g 1(-1), resulting in 80 % of NH4-N and 41% of PO3-P removal, at about 3 hrs of retention time. Microscopic analysis showed that amorphous crystals were mainly observed in the settled solids with waste lime addition whereas prism-like crystals were found in the system with magnesium salt added. Mass balance analysis in full-scale model plants (Q=158,880 m(3)d(-1)) based on the present experimental results revealed that nutrient recycle loading from side stream to main liquid stream would be significantly reduced. The results of the experiment reveal that reuse of industrial waste lime in a nutrient recovery system has the various advantages such as higher economical benefits and sustainable treatment of the industrial waste.


Spermine modulation of specific [3H]-gabapentin binding to the detergent-solubilized porcine cerebral cortex alpha 2 delta calcium channel subunit.
1. Recent studies have identified the [3H]-gabapentin-binding protein, purified from porcine cerebral cortical membranes, as the alpha 2 delta subunit of voltage-sensitive calcium channels (Gee et al., 1996). The present study investigates the influence of the polyamine spermine on specific [3H]-gabapentin binding to detergent-solubilized porcine cerebral cortical membranes. 2. Spermine, spermidine, 1,10 diaminodecane, Mg2+ and Zn2+, all divalent cations, displaced [3H]-gabapentin binding to detergent-solubilized membranes in a concentration-dependent manner with a maximal inhibition of 65-75%. Radioligand binding studies showed that spermine did not directly interact with the [3H]-gabapentin-binding site. Spermine inhibited [3H]-gabapentin binding by interacting with a polyamine-sensitive allosteric site on the membrane protein. The steep concentration-dependence of spermine inhibition of [3H]-gabapentin binding may suggest multi-site co-operativity. 3. Prolonged dialysis of cerebral cortical membranes and Tween 20-solubilized membranes resulted in a > 2.0 fold increase in [3H]-gabapentin binding. The increase in binding was due to the removal of a heat stable, low molecular weight (< 12,000Da) endogenous molecule which influences [3H]-gabapentin binding competitively. 4. Dialysis of detergent-solubilized cerebral cortical membranes also resulted in a decrease in the maximum inhibition of [3H]-gabapentin binding by spermine. Since the rates of the increase in [3H]-gabapentin binding and the loss of the ability of spermine to inhibit [3H]-gabapentin binding on dialysis were different it was inferred that a second endogenous ligand was removed during dialysis. 5. During initial steps of purification of the [3H]-gabapentin-binding protein there was a decrease in the maximum inhibition of [3H]-gabapentin binding by spermine. The loss of the second endogenous molecule during initial purification would reasonably explain the reduction in inhibition of binding by spermine. However, spermine stimulation of [3H]-gabapentin binding to material that eluted from the gel-filtration column later in the purification scheme does not appear to be due to removal of a dialysable endogenous factor or to the dissociation of other calcium channel subunit(s). 6. Adding back dialysate, before or after boiling, to detergent solubilized membranes resulted in a dose-dependent restoration of the inhibition of [3H]-gabapentin binding and of the maximal inhibition [3H]-gabapentin binding by spermine. This result is consistent with the re-addition of two endogenous heat stable ligands. 7. The findings that [3H]-gabapentin binding to the pure alpha 2 delta subunit was stimulated by spermine indicates that the alpha 2 delta subunit of voltage-sensitive calcium channels bears a modulatory spermine site. Such a spermine site has not been identified before. Spermine stimulation of [3H]-gabapentin binding to the purified protein was reversed to inhibition after adding back dialysate. Thus the inhibitory spermine effect in membranes is also probably due to one or more modulatory sites on the alpha 2 delta subunit.


Topics in histopathology of sweat gland and sebaceous neoplasms.
This article reviews several topics regarding sweat gland and sebaceous neoplasms. First, the clinicopathological characteristics of poroid neoplasms are summarized. It was recently reported that one-fourth of poroid neoplasms are composite tumors and one-fourth are apocrine type lesions. Recent progress in the immunohistochemical diagnosis of sweat gland neoplasms is also reviewed. CD117 can help to distinguish sweat gland or sebaceous tumors from other non-Merkel cell epithelial tumors of the skin. For immunohistochemical differential diagnosis between sweat gland carcinoma (SGC) other than primary cutanesous apocrine carcinoma and skin metastasis of breast carcinoma (SMBC), a panel of antibodies may be useful, including p63 (SGC+ , SMBC- ), CK5/6 (SGC+ , SMBC- ), podoplanin (SGC+ , SMBC- ) and mammaglobin (SGC- , SMBC+ ). Comparison of antibodies used for immunohistochemical diagnosis of sebaceous carcinoma (SC) suggests that adipophilin has the highest sensitivity and specificity. Some authors have found that immunostaining for survivin, androgen receptor and ZEB2/SIP1 has prognostic value for ocular SC, but not extraocular SC. In situ SC is rare, especially extraocular SC, but there have been several recent reports that actinic keratosis and Bowen's disease are the source of invasive SC. Finally, based on recent reports, classification of sebaceous neoplasms into three categories is proposed, which are sebaceoma (a benign neoplasm with well-defined architecture and no atypia), borderline sebaceous neoplasm (low-grade SC; an intermediate tumor with well-defined architecture and nuclear atypia) and SC (a malignant tumor with invasive growth and evident nuclear atypia).


Production of Plasmodium vivax enolase in Escherichia coli and its protective properties.
Plasmodium vivax predominates in South-East Asia and the American continent, causes significant morbidity and inflicts a huge socioeconomic burden. Sequencing completion of the Plasmodium vivax genome and transcriptome provides the chance to identify antigens. Enolase is the eighth enzyme in the glycolytic pathway, which, apart from its glycolytic function, also possess antigenic properties and is present on the cell wall of many invasive organisms, such as Candida albicans. In order to assess whether enolase of Plasmodium vivax is also antigenic, in this study, we first reported the expression and purification of recombinant Plasmodium vivax enolase (r-Pven) in Escherichia coli, using prokaryotic expression vector. The r-Pven was expressed in soluble form in E. coli, and the expression was verified by SDS-PAGE and western blotting analysis. The r-Pven was purified to 90% purity by nickel-nitrilotriacetic acid (Ni2+-NTA) resin chromatography. For reactivity with r-Pven, compared with the average values of the reactivity of control serum samples, the average values of the reactivity of 99 individual serums from vivax malaria patients appeared higher, and there was significant difference between them (p=0.0117<0.05). Mice anti-r-Pven antibodies inhibited the growth of in vitro cultures of P. falciparum. Mice immunized with r-Pven showed protection against a challenge with the mouse malarial parasite Plasmodium berghei. The antibodies raised against r-Pven were specific for Plasmodium and did not react to the host tissues. These observations established Plasmodium vivax enolase to be a potential protective antigen.


Zebrafish stm is involved in the development of otoliths and of the fertilization envelope.
Using an in vivo assay, we selected 11 genes that were highly upregulated during the induction of ovulation in zebrafish using microarray analysis and RNA sequencing. The starmaker gene (stm) was one of these genes. Although stm has been previously reported to be involved in otolith formation during the early development of zebrafish, we detected its expression in eggs and showed that stm was related to fertilization by establishing an stm gene knockout strain using the CRISPR/Cas9 system. Further phenotypic analysis of stm knockout fish was conducted in this study. With a higher nonfertilization rate, the stm mutant strain showed an extremely low survival rate. Otoliths of stm homozygous mutant zebrafish showed abnormal morphology in embryos and adult fish. However, fish did not show any abnormalities in swimming behaviour in either embryos or adults. Stm proteins were detected on the chorion of ovulated eggs before spawning. Fibre-supported knob-like structures on the fertilization envelope (FE) also showed abnormal structures in stm mutants. The Stm protein is necessary for otolith formation, and a lack of Stm causes abnormal otolith formation. The partial defect of otolith formation does not cause defects in swimming behaviour. The Stm protein is expressed in the chorion and is responsible for the formation of fibre-supported knob-like structures on the FE. It was suggested that a lack of Stm caused a lower fertilization rate due to inadequate formation of the FE. In zebrafish, the protein Starmaker (Stm) was identified as having a role in ovulation. Stm is also known to be required for the formation of ear stones (otoliths) which are needed to keep the body in balance. Zebrafish lacking Stm were produced by genome editing. As expected, Stm-deficient fish formed abnormal otoliths. To investigate the role of Stm in ovulation, fertilization and early development, we tried mating of Stm mutants and observed their juveniles. Although no problem found in ovulation, we found low fertilization rate and abnormal structure of knob-like structure (small pit) on the egg membrane. Survival rate of embryos with abnormal egg membrane was extremely low. It was demonstrated that Stm protein is necessary to form the functional egg membrane to protect embryos from the outside environment.


The relationship between muscle fatigue and balance in the elderly.
To investigate the effect of gastrocnemius muscle fatigue on postural control ability in elderly people. Twenty-four healthy elderly people participated in this study. The postural control ability of single leg standing was evaluated with Health Improvement & Management System (HIMS) posturography before and after fatiguing exercises. After evaluating initial postural control ability, the maximal voluntary contraction (MVC) of ankle plantarflexion was assessed using a surface electromyogram from the medial belly of the gastrocnemius muscle. After a 5-minute resting period, subjects began submaximal isometric ankle plantarflexion (40% MVC) until 40% of MVC was dropped below 95% for 5 seconds, or subject couldn't continue working out due to muscle fatigue. And postural control ability was assessed after fatiguing exercise. The mean deviation of center of pressure (COP), length of COP movement, occupied area of COP were measured, and analyzed by paired t-test. Mediolateral deviation, length of COP movement, and area of COP occupied were increased after fatiguing exercise of the gastrocnemius muscle. Anteroposterior deviation and length of COP movement were also increased, but had low statistical significance. These findings suggest that the gastrocnemius muscle fatigue affects mediolateral stability and accuracy during single leg standing in elderly people. Therefore muscle endurance training is necessary to prevent falls in elderly people.


Thermodynamics of Bioreactions.
Thermodynamic principles have been applied to enzyme-catalyzed reactions since the beginning of the 1930s in an attempt to understand metabolic pathways. Currently, thermodynamics is also applied to the design and analysis of biotechnological processes. The key thermodynamic quantity is the Gibbs energy of reaction, which must be negative for a reaction to occur spontaneously. However, the application of thermodynamic feasibility studies sometimes yields positive Gibbs energies of reaction even for reactions that are known to occur spontaneously, such as glycolysis. This article reviews the application of thermodynamics in enzyme-catalyzed reactions. It summarizes the basic thermodynamic relationships used for describing the Gibbs energy of reaction and also refers to the nonuniform application of these relationships in the literature. The review summarizes state-of-the-art approaches that describe the influence of temperature, pH, electrolytes, solvents, and concentrations of reacting agents on the Gibbs energy of reaction and, therefore, on the feasibility and yield of biological reactions.


[Echo-Doppler diagnosis of mitral stenoses].
The Doppler spectrum diagnosis of mitral stenosis includes two stages: positive diagnosis and diagnosis of gravity. The positive diagnosis rests on the increase of the maximal velocity of the transmitral flow, the persistence of this acceleration during the entire diastole with decrease of the deceleration gradient, more marked when the stenosis is narrower, and the enlargement of the spectrum. The diagnosis of gravity rests on the measurement of the mean gradient by applying Bernouilli's equation and the point by point quadratic transformation of the transmitral velocity curve obtained by Doppler and the measurement of the mitral area either by measurement of the half-decrease time in pressure or by applying the continuity equation. This last method advocated by Nakatani is particularly interesting in case or significant aortic insufficiency which often invalidates the application of T1/2.


[Sensitivity to antibiotics of 64 strains of Stomatococcus mucilaginosus isolated in human clinical cases. Demonstration of erythromycin resistance].
Susceptibility to fifteen antibiotics of 64 stains of Stomatococcus mucilaginosus isolated from bronchial secretions was tested by susceptibility antibiotics diffusion and MIC method. Sixteen phenotypic profiles were determined by MIC. Some of these profiles and the spontaneous loss of resistance to erythromycin indicate plasmidic origin of this resistance.


Serological follow-up after treatment of Borrelia arthritis and acrodermatitis chronica atrophicans.
To study the serological response to Borrelia burgdorferi after treatment of late Lyme borreliosis, consecutive serum samples from 20 patients with Borrelia arthritis and 21 with acrodermatitis chronica atrophicans were analysed with capture IgM ELISA and indirect IgG ELISA, both using B. burgdorferi flagella as antigen. Seven patients had positive IgM OD values, whereas all 41 had positive IgG OD values before therapy. In the majority, highly elevated IgG OD values were seen. All patients improved after antibiotic therapy, 32 recovering completely, while 9 had sequelae. At follow-up after 6 months to 5 years, 4/7 patients became negative IgM ELISA, whereas 3 still had slightly elevated IgM OD values 6 months, 1 year and 4.5 years, respectively, after therapy. Only one patient became negative in IgG ELISA during follow-up, although a significant decline in IgG OD values was seen in 22 of the remaining 40 initially IgG-positive patients. The serological response after successful treatment of Borrelia arthritis and acrodermatitis chronica atrophicans may persist for several years even with highly elevated IgG OD values in patients who have recovered completely.


Liver procurement for orthotopic transplantation: an analysis of the Pittsburgh experience.
The incidence of prospective organ donors in the United States and the techniques which are to used to guarantee their optimal use after identification are analyzed. Attitudes of the public and health professionals toward organ donation are discussed. The organization of the Pittsburgh Organ Procurement Agency and its relationship to other such agencies is described. Finally, the presently used techniques of liver salvaging and preservation are outlined.


Antinuclear antibody negative systemic lupus erythematosus presenting as bilateral facial paralysis.
Cranial neuropathy, and particularly facial palsy, is a rare occurrence in patients with systemic lupus erythematosus (SLE). We describe a 16-year-old female who developed bilateral facial palsy concomitant with cutaneous bullous eruption, alopecia, mucosal ulcers, arthritis, lymphadenopathy, parotid enlargement, and proteinuria. The lack of positive antinuclear antibody (ANA) at presentation obscured the diagnosis. Her followup course clarified the diagnosis of SLE. We believe this is the first report of ANA negative SLE presenting as bilateral facial palsy.


Bitumen, polycyclic aromatic hydrocarbons and vehicle exhaust: exposure levels and controls among Norwegian asphalt workers.
To characterize exposures of asphalt workers in Norway and to evaluate exposure control measures. Representative asphalt paving and mixing operations were monitored in Norway in 1991-92 for exposures to bitumen fume, organic vapor, polycyclic aromatic hydrocarbons (PAHs) and vehicle exhaust (NO2, CO). Linear regression was used to evaluate introduced control measures. A total of 320 samples of airborne organic matter were gathered (279 from paving). Median personal bitumen fume measurements ranged from 0.03 to 0.15 mg/m3 and were similar in paving and asphalt mixing. According to principal component analysis, there were three independent sets of PAHs: (i) PAHs lighter than 228 g/mol; (ii) 4- to 6-ring PAHs non-detectable in 80-90% of samples; and (iii) naphthalene. Some NO2 (1/49) and CO (12/58) concentrations near paving equipment exceeded 15 min exposure limits, 2 and 25 p.p.m., respectively. Changing sampling methods midway through the study had a significant impact on the measured bitumen fume and organic vapor levels. For pavers, lower application temperatures reduced organic vapor, but not bitumen fume, exposures. Retrofitting a paving machine produced at least a 5-fold reduction in exposure to airborne organic matter. Work in tunnels increased PAH exposures, but general ventilation partially counteracted this effect. The observed exposure levels indicate that some potentially hazardous exposures may have occurred during paving in Norway. Bitumen fume, organic vapor and PAH exposures can be reduced using appropriate engineering control measures.


Sensory and sympathetic disorders in chronic non-specific neck pain.
The signs of sympathetic and sensory nerve-related disorders are not widely investigated in chronic nonspecific neck pain (NNP) patients. Thus, we performed skin temperature (Tsk), evaporation and touch threshold (TT) measurements to reveal possible dysfunctions at the fingertips of NNP patients (n=60) compared with healthy controls (n=11). Neck pain intensity was the main modifier of Tsk, and age the main modifier of TT in a multivariate model. On comparisons of the subgroups of NNP patients with unilateral (n=26) and bilateral (n=34) symptoms and controls, TT differed and Tsk tended to differ, the unilateral pain patients being found to demonstrate higher TT values on both sides. Interrelations between the measured parameters were found in the controls, but not in the patients. The NNP patients exhibited signs of functional impairment of innervation reflected in changes in tactile sensitivity and vasoactive sympathetic function. These changes may be based on both central and peripheral mechanisms, which possibly differ in patients with unilateral and bilateral symptoms.


Sugar pucker geometries at the intercalation site of propidium diiodide into miniature RNA and DNA duplexes in solution.
We have evaluated the sugar pucker geometry at the intercalation site of propidium diiodide into the self-complementary dinucleoside monophosphate duplexes cytidylylguanosine and deoxycytidylyldeoxyguanosine as a function of the nucleotide/drug ratio in aqueous solution. Our solution results support the observation by Sobell and coworkers [Sobell, H.M., Tsai, C.C., Jain, S.C. & Gilbert, S.G. (1977) J. Mol. Biol. 114, 333--365] of a C3' endo (3'-5')C2' endo sugar pucker geometry in the 2:2 intercalation complex of ethidium bromide into the iodocytidylylguanosine duplex in the crystalline state. We demonstrate further that the mixed sugar pucker observed for the intercalation of propidium diiodide into the miniature RNA duplex in solution persists in the intercalative complex of this trypanocidal drug into the corresponding miniature DNA duplex in solution.