Cystic fibrosis clinical characteristics associated with dornase alfa treatment regimen change.
When the chronic respiratory therapy dornase alfa was made commercially available for cystic fibrosis (CF) more than 20 years ago, two regimens were approved: 2.5 mg inhaled once daily (QD) or twice daily (BID). In the intervening years, there has been little guidance as to when to use each regimen. We have studied clinical practice patterns captured in the Epidemiologic Study of CF (ESCF) during the decade following dornase alfa approval (1994-2005) to better understand clinical characteristics associated with QD versus BID dornase alfa use. Methods We studied the characteristics of ESCF patients who received either dornase alfa regimen for at least 12 months and who were then switched to the alternate regimen for at least 6 months and who had adequate data available around the time of the switch. Average lung function and weight-for-age (WFA) z-scores, numbers of intravenous (IV) antibiotic-treated pulmonary exacerbations, and prevalence of signs and symptoms were determined for 6-month periods capturing the beginning (FIRST) and the end (LAST) of the initial regimen, the 6 months preceding the final 6 months of the initial regimen (PRIOR), and the beginning of the second regimen (POST). Changes in values from FIRST to LAST, PRIOR to LAST, and LAST to POST were studied to better understand clinical scenarios associated with decisions to change regimens. A total of 1342 QD and 574 BID regimens were studied with median durations of 3.19 and 2.09 years, respectively. On average, patients beginning BID regimens had worse lung function and a greater number of pulmonary exacerbations treated with IV antibiotics than those beginning QD regimens. However, by the time of regimen switch, patients switching from QD to BID dornase alfa had experienced substantial deterioration with respect to pulmonary exacerbations and signs and symptoms, whereas patients switching from BID to QD had not. Interestingly, incidence of IV-treated pulmonary exacerbations and signs and symptom prevalence decreased for both populations after regimen switch. We have studied populations of patients with CF receiving dornase alfa who were switched between regimens to characterize clinical course. Our results suggest that the most common clinical attribute associated with switching from QD to BID dornase alfa was a marked deterioration in stability characterized by increased incidence and frequency of pulmonary exacerbation. For this population, deterioration in lung function did not appear to be a driver for this switch. In contrast, patients receiving BID dornase alfa who were ultimately switched to QD appeared to be clinically stable, on average, suggesting that treatment burden and cost may have been drivers of the decision to switch regimens.


Transdermal fentanyl for the management of cancer pain: a survey of 1005 patients.
Transdermal fentanyl was released in Germany in 1995. From October 1996 to February 1998 transdermal treatment was documented for 1005 patients (506 men and 499 women with a mean age of 60 years, range 20-92 years) with chronic pain in an open survey including 290 physicians from hospitals and general practitioners throughout Germany. Most patients suffered from cancer pain and only 11 patients had chronic pain from non-malignant disease. Physicians were asked to complete a questionnaire for patients treated with transdermal fentanyl on initiation of therapy (day 0), and days 3, 6, 18, 30 thereafter, followed by monthly follow-up intervals. Patients were asked to complete a pain diary. Transdermal therapy was documented from day 0 for 824 patients, while 181 patients had been treated with transdermal fentanyl before admission in the survey. Most of the other 824 patients had been treated with other step 3 opioids (55% of the patients) or step 2 opioids (23%) before conversion to transdermal fentanyl, whereas 8% had been treated only with non-opioids and 14% had received analgesics only as required or not at all before initiation of transdermal therapy. The most important reasons for switching to transdermal opioid therapy were insufficient pain relief with the previous medication followed by a variety of gastrointestinal symptoms impeding oral analgesic therapy. Initial fentanyl doses ranged from 0.6 to 9.6 mg/day (25 to 400 microg/h) with a median of 1.2 mg/day (50 microg/h). Median doses slowly increased throughout the observation period to 2.4 mg/day (100 microg/h) after 4 months of treatment. Most patients continued transdermal therapy until the time of death (47% of patients). Other reasons for discontinuation were inadequate pain relief (10%), pain relief with other analgesic regimens (10%), other symptoms than pain (5%), rejection of transdermal therapy by the patient (6%) or miscellaneous (16%). Adverse events were documented as the reason for discontinuation of transdermal therapy in 49 patients (5%). Dyspnoea was documented for seven patients as the reason for discontinuation. One of these patients, as well as another patient with an episode of apnoea, had to be treated with artificial respiration for several hours, but both patients recovered without sequelae. Transdermal therapy with fentanyl was safe and efficient in this national survey. Transdermal fentanyl can be recommended for treatment of moderate to severe cancer pain and probably may even be used as a first-line drug on step 3 of the World Health Organization recommendations in selected patient groups.


Identification of a terphenyl derivative that blocks the cell cycle in the G0-G1 phase and induces differentiation in leukemia cells.
To further explore the SAR of resveratrol-related trans-stilbene derivatives, here we describe the synthesis of (a) a series of 3,5-dimethoxy analogues in which a variety of substituents were introduced at positions 2', 3', 4', and 5' of the stilbene scaffold and (b) a second group of derivatives (2-phenylnaphthalenes and terphenyls) that incorporate a phenyl ring as a bioisosteric replacement of the stilbene alkenyl bridge. We thoroughly characterized all of the new compounds with respect to their apoptosis-inducing activity and their effects on the cell cycle. One of the new derivatives, 13g, behaved differently from the others, as it was able to block the cell cycle in the G(0)-G(1) phase and also to induce differentiation in acute myelogenous leukemia HL60 cells. Compared to resveratrol, the synthetic terphenyl 13g showed a more potent apoptotic and differentiating activity. Moreover, it was active on both multidrug resistance and Bcr-Abl-expressing cells that were resistant to resveratrol.


Comparison and contrasts between the active site PKs of Mn-superoxide dismutase and those of Fe-superoxide dismutase.
The Fe- and Mn-containing superoxide dismutases catalize the same reaction and have almost superimposable active sites. Therefore, the details of their mechanisms have been assumed to be similar. However, we now show that the pH dependence of Escherichia coli MnSOD activity reflects a different active site proton equilibrium in (oxidized) Mn(3+)SOD than the event that affects the active site pK of oxidized FeSOD. We find that the universally conserved Tyr34 that has a pK above 11.5 in Fe(3+)SOD is responsible for the pK near 9.5 of Mn(3+)SOD and, thus, that the oxidized state pK of Mn(3+)SOD corresponds to an outer-sphere event whereas that of Fe(3+)SOD corresponds to an inner sphere event [Bull, C.; Fee, J. A. J. Am. Chem. Soc. 1985, 107, 3295-3304]. We also present the first description of a reduced-state pK for MnSOD. Mn(2+)SOD's pK involves deprotonation of Tyr34, as does Fe(2+)SOD's pK [Sorkin, D. L.; Miller A.-F. Biochemistry 1997, 36, 4916-4924]. However, the values of the pKs, 10.5 and 8.5 respectively, are quite different and Mn(2+)SOD's pK affects the coordination geometry of Mn(2+), most likely via polarization of the conserved Gln146 that hydrogen bonds to axially coordinated H(2)O. Our findings are consistent with the different electronic configurations of Mn(2+/3+) vs Fe(2+/3+), such as the stronger hydrogen bonding between Gln146 and coordinated solvent in MnSOD than that between the analogous Gln69 and coordinated solvent in FeSOD, and the existence of weakly localized H(2)O near the sixth coordination site of Mn(2+) in Mn(2+)SOD [Borgstahl et al. J. Mol. Biol. 2000, 296, 951-959].


Comparison of sublingual and oral prazepam in normal subjects. II. Pharmacokinetic and pharmacodynamic data.
The pharmacokinetic profiles of oral and sublingual administrations of prazepam 20 mg to 5 normal volunteers were compared in order to explain the clinical observation that sublingual prazepam appears to exhibit sedative properties when compared to the same dose of oral prazepam. Blood samples for pharmacokinetic evaluation were collected just before drug intake and 7.5, 15, 22.5, 30, 45, 60, 90 min, 2, 3, 5, 6, 7, 8, 9, 10 and 24 h after drug intake. The study was performed in double-blind and crossover conditions. Serum levels of prazepam and its major metabolite N-desmethyl-diazepam were measured by HPLC. No prazepam was detected at a concentration higher than 20 ng/ml (limit of detection) whereas N-desmethyl-diazepam reached concentrations around 140 ng/ml. To correlate this observation with the clinical data, the affinity of prazepam and N-desmethyl-diazepam was compared measuring their ability to displace 50% of 3H-flunitrazepam bound to benzodiazepine receptors contained in synaptosomal preparation obtained from rat brain. N-desmethyl-diazepam was 17-fold more potent than prazepam. This data suggests that prazepam is a pro-drug which is transformed to the active compound N-desmethyl-diazepam and that the difference in clinical observation with both administrations could be correlated to N-desmethyl-diazepam concentration-time curves. Nevertheless, the comparison of the area under the N-desmethyl-diazepam serum concentration-time curves, the maximum concentrations, the times when the maximum concentrations were observed and the times needed to detect a significant level after oral and sublingual administration did not show statistical difference.(ABSTRACT TRUNCATED AT 250 WORDS)


Poly(vinyl alcohol)/halloysite nanotubes bionanocomposite films: Properties and in vitro osteoblasts and fibroblasts response.
In this study, transparent poly(vinyl alcohol) (PVA) and PVA/halloysite nanotubes (HNTs) bionanocomposite films were prepared by solution casting and glutaraldehyde (GA) crosslinking. The surface topography and chemistry of the films were characterized by atomic force microscopy (AFM) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, respectively. Blending with HNTs induced changes in nanotopography and surface chemistry of PVA films. The mechanical properties of PVA were enhanced by the incorporated HNTs. The stain-induced crystallization was confirmed by DSC after tensile test. MC3T3-E1 osteoblast-like and NIH 3T3 fibroblast cells were cultured on neat PVA and PVA/HNTs films to evaluate the effects of surface nanotopography and composition on cell behavior. The observations indicated that MC3T3-E1 cell behavior strongly responded to surface nanotopography. On nanotube-dominant surface, cells exhibited a significantly higher level of adhesion than on neat PVA film, whereas neat PVA showed higher degree of osteoblast proliferation compared with PVA/HNTs. In vitro fibroblasts response demonstrated that both neat PVA and PVA/HNTs nanocomposite films were biocompatible and PVA/HNTs films favored to fibroblasts attach and growth below 7.5 wt % of HNTs incorporated. In summary, these results provided insights into understanding of PVA and PVA/HNTs bionanocomposite films in potential applications in bone tissue engineering and drug delivery systems.


Inadequate availability of pharmacological treatment for affective disorders in New Zealand.
Both BAD and unipolar depression are common, serious and, in some cases, chronic conditions which often require long term pharmacotherapy. Drug side effects can be severe, contribute to poor compliance and are therefore a factor in maintaining illness and precipitating relapse. Treatment resistance is common. Current evidence suggests that a number of pharmacological agents which are available in other countries (and in some cases have been for many years) may be useful when side effects or treatment resistance occur. In some cases these alternatives are part of recommended algorithms for treatment. In New Zealand, when side effects occur, the options are limited and the problem of treatment resistance is usually approached by using poorly researched combinations of the currently available drugs, thus increasing the likelihood of side effects and adverse drug interactions. The current system is failing to provide appropriate or adequate treatment for people suffering from affective disorders and should be urgently reviewed.


Proliferation, Apoptosis and Invasion effects of mistletoe alkali on human osteosarcoma U2OS in vitro.
To evaluate the effects of mistletoe alkali on human Osteosarcoma cells (U2OS) in vitro. Osteosarcoma is the most common primary malignant tumor of bone tumor, although there are a lot of therapies such as surgery, radiotherapy and chemotherapy, its prognosis is still very poor. There is increasing interest in the protective biological function of natural antioxidants contained in Chinese medicinal herbs, which are candidates for the prevention of tumors. Mistletoe alkali is one of the compounds extracted from Viscum coloratum (Komar.) Nakai, one kind of mistletoe, whose extracts contribute to the improvement of the prognosis of patients with malignancies. The effect of mistletoe alkali on the growth of U2OS cells was compared with 5-FU, using a Cell Counting Kit-8 (CCK-8). The influence of mistletoe alkali on U2OS's proliferation and apoptosis were tested by TUNEL staining and immunocytochemical (ICC) staining of caspase 3 and proliferating cell nuclear antigen (PCNA). Additionally, the invasion ability of U2OS cells was detected using a Boyden chamber trans-well migration assay. CCK-8 assays gave an IC50 of 7μg/ml for mistletoe alkali. Compared to 5-FU, mistletoe alkali inhibited U2OS proliferation and induced apoptosis more effectively. The invasion ability of U2OS was also weaker in mistletoe alkali than in 5-FU. Mistletoe alkali significantly inhibited growth and invasion abilities of U2OS cells and induced their apoptosis in vitro. Mistletoe alkali may be a more effective drug for Human Osteosarcoma than the standard chemotherapeutic drug 5-FU.


Measuring quality of life in paediatric patients.
The purpose of this paper is to highlight important considerations in the measurement of health-related quality of life (HR-QOL) in paediatric populations. Considerations specific to the evaluation of HR-QOL in children include children's understanding of the questions being asked, their understanding of their own disease, using parents as proxies, time perception problems and simply the fact that children are continually changing. We provide a review of the currently available literature regarding paediatric HR-QOL assessments to examine the different instruments and approaches taken to assess HR-QOL in paediatrics. Asthma-specific measures are discussed as examples of condition-specific HR-QOL instruments because of the considerable amount of methodological and developmental work that has been conducted in this disease. Our search strategy revealed 15 main generic and 5 main asthma-specific instruments that met our criteria for inclusion. The main points high-lighted for each instrument are the description of domains, respondent (i.e. the child, parent or clinician), age group, number of items, format of instrument (usually self-administered or by interview), original country and language, and the existence of translations. For the various studies in which the different instruments are used, the issues of patient population tested, sample size, reliability and validity are addressed. Although this paper does not attempt to be an exhaustive study of paediatric HR-QOL instruments, we provide an overview of the main generic and asthma-specific instruments, as well as an examination of the different methods used in assessing paediatric HR-QOL. Many challenges exist in the measurement of HR-QOL in paediatric patients. With increased attention to the considerations high-lighted, the field will continue to grow, and the usefulness and application of HR-QOL measures in paediatric patients is likely to improve.


Overexpression of HES-1 is not sufficient to impose T-cell differentiation on human hematopoietic stem cells.
By retroviral overexpression of the Notch-1 intracellular domain (ICN) in human CD34+ hematopoietic stem cells (HSCs), we have shown previously that Notch-1 signaling promotes the T-cell fate and inhibits the monocyte and B-cell fate in several in vitro and in vivo differentiation assays. Here, we investigated whether the effects of constitutively active Notch-1 can be mimicked by overexpression of its downstream target gene HES1. Upon HES-1 retroviral transduction, human CD34+ stem cells had a different outcome in the differentiation assays as compared to ICN-transduced cells. Although HES-1 induced a partial block in B-cell development, it did not inhibit monocyte development and did not promote T/NK-cell-lineage differentiation. On the contrary, a higher percentage of HES-1-transduced stem cells remained CD34+. These experiments indicate that HES-1 alone is not able to substitute for Notch-1 signaling to induce T-cell differentiation of human CD34+ hematopoietic stem cells.


Association of asthma exacerbations with paper mulberry (Broussenetia papyrifera) pollen in Islamabad: An observational study.
Although the role of airborne plant pollen in causing allergic rhinitis has been established, the association of concentrations of paper mulberry (Broussenetia papyrifera) pollens in the air and incidence of asthma exacerbations has not, despite an observed increase in the number of asthma patients attending physician clinics and hospital Accident and Emergency (A&E) Departments during the paper mulberry pollen season. We aimed to assess the association between paper mulberry pollen concentrations (typically peaking in March each year) and asthma exacerbations in the city of Islamabad. We used three approaches to investigate the correlation of paper mulberry pollen concentration with asthma exacerbations: A retrospective analysis of historical records (2000-2019) of asthma exacerbations of patients from the Allergy and Asthma Institute, Pakistan (n = 284), an analysis of daily nebulisations in patients attending the A&E Department of the Pakistan Institute of Medical Sciences (March 2020 to July 2021), a prospective peak expiratory flow rate (PEFR) diary from participants (n = 40) with or without asthma and with or without paper mulberry sensitisation. We examined associations between pollen data and asthma exacerbations using Pearson correlation. We found a strong positive correlation between mean paper mulberry pollen counts and clinical records of asthma exacerbations in patients sensitised to paper mulberry (Pearson correlation coefficient (r) = 0.86; P < 0.001), but not in non-sensitised patients (r = 0.32; P = 0.3). There was a moderate positive correlation between monthly nebulisation counts and pollen counts (r = 0.56; P = 0.03), and a strong negative correlation between percent predicted PEFR and pollen counts in sensitised asthma patients (r = -0.72, P < 0.001). However, these correlations were of low magnitude in the non-sensitised asthma (r = -0.16; P < 0.001) and sensitised non-asthma (r = -0.28; P < 0.001) groups. Our three approaches to analysis all showed an association between high paper mulberry pollen concentration in Islamabad and asthma exacerbations. Predicting pollen peaks could enable alerts and mobilise strategies to proactively manage these peaks of asthma exacerbations.


Piroxicam loaded polymer hybrid microspheres based tablets with modified release kinetics: Development, characterization and in vivo evaluation.
Piroxicam (PC) is a non-steroidal anti-inflammatory drug characterized by poor aqueous solubility and reported to cause and impart crucial GIT irritation, bleeding, peptic and duodenal ulcer. Engineering of PC loaded microcapsules and its surface modification using different polymers has become the popular approach to address the said issues. The purpose of the study was to develop new PC loaded gastro-protective polymer hybrid microspheres (PHM) with subsequent conversion to tablet dosage form having modified dissolution rate and improved bioavailability. The crystallinity of the PC loaded PHM were established through powder X-ray diffraction. The optimised microspheres, PC-M1 with particle size 32±3.0μm, entrapment efficiency 83.78±2.5% and in vitro drug release 87.1±2.6% were further subjected to tablets development and in vivo evaluation. The in vitro drug release study conducted for PHM at pH media 1.2 and 6.8 demonstrated retarded and enhanced drug release rates (P<0.001) respectively. Both accelerated and real time stability studies confirmed stability of the PC loaded PHM based tablets. A substantial improvement in the drug plasma concentration 12.6±2.36 (P<0.001) was observed for the produced tablets compared to the marketed formulations.


Secondary cutaneous manifestations of acute schistosomiasis mansoni.
The secondary cutaneous manifestations of the initial phase of schistosomiasis mansoni were studied in 34 patients who had been infected simultaneously in the same location. Sixteen of the patients developed angioedema and/or urticaria, generally of short duration and of mild intensity and usually about 30 days post-infection. There was no apparent association between the occurrence of these skin manifestations and the patients' worm burdens, blood eosinophilias or areas of immediate reaction to an intradermal inoculation with worm antigen. Other factors, particularly host immunological reactivity, are thought to be important elements in the genesis of the manifestations.


Intracytoplasmic crystalloid structures in a malignant fibrous histiocytoma: ultrastructural and cytochemical study.
Crystalloid structures were frequently observed in the cytoplasm of the tumor cells of a malignant fibrous histiocytoma arising in the left leg of a 71-year-old female. These structures were located in the cytoplasm of the fibroblastlike and histiocyte-like tumor cells. The structures consisted of an aggregate of dense granules without unit membrane. Neither glycoproteins nor polysaccharides were detected in these structures on sections stained with chromic acid-phosphotungstic acid or periodic acid-thiocarbohydrazide-silver proteinate. On sections from acrylate-embedded specimens, the structures were easily digested by trypsin and protease but were not sensitive to RNase. Although the significance and origin of these structures remain obscure, the results indicate that the crystalloid structures in the present study are mainly composed of proteinaceous substance.


Normosmic idiopathic hypogonadotropic hypogonadism: update on the genetic background and future challenges.
What controls puberty remains largely unknown, and current gene mutations account for only about one-third of the apparently genetic cases of idiopathic hypogonadotropic hypogonadism. Lately, important developments have occurred in this field. The neuroendocrine control of reproduction in all mammals is governed by a hypothalamic neural network of approximately 1500 gonadotropin-releasing hormone (GnRH) secreting neurons that control the activity of the reproductive axis across life. Recently, the syndrome of human GnRH deficiency, either with anosmia, termed Kallmann syndrome, or with a normal sense of smell, termed normosmic idiopathic hypogonadotropic hypogonadism, has proven to be important disease models that have revealed much about the abnormalities that can befall the GnRH neurons as they differentiate, migrate, form networks, mature and senesce. Mutations in several genes responsible for these highly coordinated developmental processes have thus been unearthed by the study of this prismatic disease model. These genetic studies have opened up a new chapter in the physiology and the pharmacology of the gonadotropic axis.


Reliability of knee flexor peak torque measurements from a standardized test protocol on a Kin/Com dynamometer.
The test-retest reliability of a specific test protocol for the measurement of peak torque of the knee flexors using a Kin/Com dynamometer was evaluated. The maximum voluntary torque generated by the left knee flexors during constant velocity resisted-muscle shortening (RMS) and muscle lengthening (RML) was measured in a sitting position in 11 healthy women with no history of knee pathology. Each subject performed two tests at each of two velocities (30 degrees/sec and 180 degrees/sec) in a single session. All subjects repeated these four tests one week later. A test consisted of four complete RMS/RML cycles through a range of 65 degrees. The peak torque generated from each test was used to measure test-retest reliability. All data were gravity compensated. Intraclass correlation coefficients (ICCs) were calculated from ANOVA tests for RML and RMS at both velocities. The within sessions ICCs ranged from .94 to .98 for 30 degrees/sec and from .92 to .97 at 180 degrees/sec. The ICCs between sessions were generally lower and ranged from .79 to .90 for 30 degrees/sec, and from .75 to .88 for 180 degrees/sec. It is concluded that using these test protocols, peak torques for both RMS and RML can be measured with a high degree of reliability at two commonly used velocities.


Mutational analysis of the high-affinity BvgA binding site in the fha promoter of Bordetella pertussis.
In order to define a consensus binding sequence for the response regulator BvgA, we have undertaken a systematic analysis of contributions made by each nucleotide within the heptad half-sites that are present in an inverted orientation at the promoter for the fha operon. Using in vitro binding assays, we examined the full complement of 21 single point mutations symmetrically arranged in this heptad repeat. Both gel shift and nitrocellulose filter-binding assays provided evidence that nucleotides at positions 3 (thymidine), 4 (cytosine) and 7 (adenine) in the binding heptad contribute substantially to sequence-specific recognition by BvgA. Furthermore, a T to A conversion at position 6 reduced binding. Selected binding site mutations were introduced into a modified fha promoter and examined for their effects on BvgA activation of promoter activity in vivo. Only those substitutions most severely affecting binding in vitro affected promoter activity in vivo. The in vivo effects of substitutions that had a significant effect on binding in vitro but did not severely affect in vivo promoter activity under standard culture conditions could be detected in vivo either in combination with additional substitutions or from their effect on the sensitivity of the mutant promoters to modulation by magnesium sulphate.


Influence of Reversed Fatigue Loading on DamageEvolution of Cross-Ply Carbon Fibre Composites.
Microcrack formation and delamination growth are the main damage mechanisms in thefatigue of composites. They lead to significant stiffness loss, introduce stress concentrations andcan be the origin of subsequent damage events like buckling or fibre breakage, especially in case ofshear and compression stresses during load reversal. Fatigue experiments of carbon fibre reinforcedlaminates were conducted at several stress ratios and analysed in terms of crack and delaminationgrowth. These investigations were accompanied by microscopic imaging, digital image correlationand finite element modelling to take into account the effects of residual stresses and crack closure.It was found that residual stresses significantly change the local stress ratio in off-axis layers andlead to residual crack opening of inter fibre cracks. These cracks remain open and close under highcompression loadings only. Furthermore, crack formation under pulsating compression loadingturned out to be driven by residual stresses leading to perpendicular cracks as observed underpure tension loading. The experimental findings further confirm the severe detrimental effect oftension-compression loading on crack formation and delamination growth compared to pulsatingtension-tension or compression-compression loads.


Diabetes mellitus as a contributory factor in oral candidosis.
It has been reported that poor glycaemic control predisposes to oral candidal infection in diabetic patients. For instance, the carriage of Candida species and the density of candidal growth in the oral cavity is frequently claimed to be increased in patients with diabetes mellitus. However, the validity of these observations remains controversial. Hence, we review and discuss here the clinical data in the literature on the relationship between diabetes and oral candidal carriage and infection, and possible mechanisms associated with its pathogenicity.


Aberrant perineuronal nets alter spinal circuits, impair motor function, and increase plasticity.
Perineuronal nets (PNNs) are a specialized extracellular matrix that have been extensively studied in the brain. Cortical PNNs are implicated in synaptic stabilization, plasticity inhibition, neuroprotection, and ionic buffering. However, the role of spinal PNNs, mainly found around motoneurons, is still unclear. Thus, the goal of this study is to elucidate the role of spinal PNNs on motor function and plasticity in both intact and spinal cord injured mice. We used transgenic mice lacking the cartilage link protein 1 (Crtl1 KO mice), which is implicated in PNN assembly. Crtl1 KO mice showed disorganized PNNs with an altered proportion of their components in both motor cortex and spinal cord. Behavioral and electrophysiological tests revealed motor impairments and hyperexcitability of spinal reflexes in Crtl1 KO compared to WT mice. These functional outcomes were accompanied by an increase in excitatory synapses around spinal motoneurons. Moreover, following spinal lesions of the corticospinal tract, Crtl1 KO mice showed increased contralateral sprouting compared to WT mice. Altogether, the lack of Crtl1 generates aberrant PNNs that alter excitatory synapses and change the physiological properties of motoneurons, overall altering spinal circuits and producing motor impairment. This disorganization generates a permissive scenario for contralateral axons to sprout after injury.


Association between restrictive pulmonary disease and type 2 diabetes in Koreans: A cross-sectional study.
Diabetes is a progressive disease that increases glucose levels in the blood. While studies have shown that patients with pulmonary disease (both obstructive and restrictive pulmonary disease) have a higher prevalence of type 2 diabetes mellitus (T2DM), there have been more studies on restrictive patterns than chronic obstructive pulmonary disease. To assess whether restrictive and obstructive pulmonary diseases are associated with T2DM in Koreans. For our analysis, we used data from the Korea National Health and Nutrition Examination Survey. A total of 2830 subjects were included in this study. Spirometry results were categorized into three patterns: Normal, restrictive pulmonary disease (RPD), and obstructive pulmonary disease (OPD). The factors used as diabetic indicators (i.e. homeostatic model assessment of insulin resistance, homeostatic model assessment of beta-cell function, glycated hemoglobin, and fasting insulin) were among the highest in RPD but not in OPD. Based on multivariate logistic regression analysis, subjects with RPD were found with an increased odds ratio [OR: 1.907, 95% confidence interval (CI): 1.110-3.277] for T2DM compared with subjects with normal pulmonary function, whereas in patients with OPD, the OR had not increased. Model 4, which adjusted for the variables that could affect diabetes and pulmonary disease, showed a significant increase in the T2DM OR to RPD (OR: 2.025, 95%CI: 1.264-3.244). On the other hand, no statistically significant difference was shown in OPD (OR: 0.982, 95%CI: 0.634-1.519). RPD, not OPD, is highly associated with T2DM regardless of the risk factors of various T2DMs that can be confounds.


Host-guest supramolecular interactions in the coordination compounds of 4,4'-azobis(pyridine) with MnX2 (X = NCS–, NCNCN–, and PF6(–)): structural analyses and theoretical study.
Three new Mn(II) coordination compounds {[Mn(NCNCN)(2)(azpy)]·0.5azpy}(n) (1), {[Mn(NCS)(2)(azpy)(CH(3)OH)(2)]·azpy}(n) (2), and [Mn(azpy)(2)(H(2)O)(4)][Mn(azpy)(H(2)O)(5)]·4PF(6)·H(2)O·5.5azpy (3) (where azpy = 4,4'-azobis(pyridine)) have been synthesized by self-assembly of the primary ligands, dicyanamide, thiocyanate, and hexafluorophosphate, respectively, together with azpy as the secondary spacer. All three complexes were characterized by elemental analyses, IR spectroscopy, thermal analyses, and single crystal X-ray crystallography. The structural analyses reveal that complex 1 forms a two-dimensional (2D) grid sheet motif. These sheets assemble to form a microporous framework that incorporates coordination-free azpy by host-guest π···π and C-H···N hydrogen bonding interactions. Complex 2 features azpy bridged one-dimensional (1D) chains of centrosymmetric [Mn(NCS)(2)(CH (3)OH)(2)] units which form a 2D porous sheet via a CH(3)···π supramolecular interaction. A guest azpy molecule is incorporated within the pores by strong H-bonding interactions. Complex 3 affords a 0-D motif with two monomeric Mn(II) units in the asymmetric unit. There exist π···π, anion···π, and strong hydrogen bonding interactions between the azpy, water, and the anions. Density functional theory (DFT) calculations, at the M06/6-31+G* level of theory, are used to characterize a great variety of interactions that explicitly show the importance of host-guest supramolecular interactions for the stabilization of coordination compounds and creation of the fascinating three-dimensional (3D) architecture of the title compounds.


[Changes in the ultrastructure of synapses and neurons of the ventral horns of the spinal cord in cats with tetany as a result of the removal of the parathyroid glands].
An electron microscopic investigation on ultrastructure of synapses and ventral horns of the lumbar thickening in the spinal cord of cats with parathyroprival tetany has been performed. When motor disorders are clearly seen on the 2d - 4th days after removal of the parathyroid glands, together with the changes demonstrating functional activity of the synapses, certain irreversible degenerative changes of the "dark" type are seen in the axodendritic and axosomatic synapses. A complex of structural-metabolic changes has been revealed in the motor neurons, they have both functional-compensatory and degenerative character. It is possible to suggest that the changes revealed at parathyroprival tetany result from a disturbed metabolism and increased afferent influences.


The intranasal ostium after external dacryocystorhinostomy and the internal opening of the lacrimal canaliculi.
The purpose of this paper was to evaluate the appearance and location of the healed intranasal ostium and the internal aperture of the common canaliculus after uncomplicated external dacryocystorhinostomy (DCR). In 21 patients who underwent uncomplicated external DCR, the distances between the lacrimal puncta and the internal aperture of the common canaliculus were measured during surgery. The measurements were taken with a 1 mm diameter Bowman probe graded in millimeters. These measurements were recorded and considered the landmarks for the spatial localization of the internal aperture of the canaliculus. After surgery, under endoscopic control, the same method was used to measure the distance between the lacrimal puncta and the internal ostium, which was defined as the aperture through which it was possible to visualize the very first protrusion of the probe into the nose. The intra- and post-operative measurements were compared. Endoscopic photos of the healed endonasal ostium were also taken. The photos showed that when DCR procedures were not complicated by scarring or mucosal adhesions, the lacrimal sac became a depression perfectly integrated within the nasal mucosa. The scar at the site of junction between the nasal and the lacrimal sac mucosa appeared as a large-diameter pearl-like colored frame that surrounded the depression. In the context of the depression a small aperture, which presented a diameter of around 2 mm, could be easily visualized. The spatial location of this aperture corresponded to the internal aperture of the common canaliculus (p < 0.05).


[Diagnostic value of the enzyme dipeptidyl peptidase IV (DP IV) in abdominal cancers].
Activity changes of the enzyme dipeptidyl peptidase IV (DP IV) were observed in connection with various diseases. The increase of serum activity in case of liver diseases and the decrease of activity in tissue and serum in case of malignant diseases are known. This investigation examined serum activity of DP IV at 168 patients with malignant diseases of the gastro-intestinal system. The 5%-, 50%- and 95%-percentiles of serum activity of DP IV were determined. Age and sex did not influence the activity of DP IV as less as attendant diseases like diabetes mellitus and hypertension. Malignant diseases of the gastro-intestinal system without liver metastases do have a significantly lower serum activity of DP IV. Malignant diseases of the pancreas and the bile duct and liver metastases lead to an increase of DP IV-serum activity.


Protective effect of electrical stimulation in the deafened guinea pig cochlea.
The effect of chronic intrascalar electrical stimulation on the spiral ganglion cell survival of the ototoxically deafened guinea pig was investigated. Immediately after ototoxic drug administration, unilateral sinusoidal (1 kHz) charge-balanced electrical stimulation on a 50% duty cycle was administered for 2 hours per day, 5 days per week, at intensities from 0 (control) to 400 microAmp via an implanted scala tympani electrode. The relationship of electrically evoked middle latency response (EMLR) to stimulation protocol and cell survival was studied. At 9 weeks post-drug treatment, the animals were killed and temporal bones were prepared for morphometric analysis of spiral ganglion cell density. The subjects showed essentially complete elimination of outer hair sensory cells, with minimal remaining inner hair cells confined to apical turns. Variable loss of spiral ganglion cell populations was observed, which related to electrical stimulation. In animals that received daily unilaterally electrical stimulation, statistically significant increases in survival of spiral ganglion cells were observed in the stimulated ear, compared to the nonstimulated ear-particularly in basal cochlear regions near the electrode. Spiral ganglion cell density was a function of stimulation current intensity level. Moreover, the slope of the amplitude input/output (I/O) function of the EMLR was found to be dependent on stimulating current level. The effect of stimulation on induced survival may be dependent on a number of mechanisms, including metabolic effects of direct activation of "deafferented" spiral ganglion cells. These data support the suggestion that implantation may provide optimal benefits when performed shortly after deafness.


Representation of the visual field in the human occipital cortex: a magnetic resonance imaging and perimetric correlation.
To evaluate the retinotopic map of the human occipital cortex by correlating magnetic resonance imaging (MRI) findings with visual field defects in patients with occipital lobe infarcts and to assess the compatibility between our cliniconeuroimaging findings and the location of lesions predicted by the classic Holmes map and a revised map. Magnetic resonance images were obtained in 14 patients with occipital lobe infarcts. Visual field analysis was performed with tangent screen, the Goldmann perimeter, and the Humphrey Field Analyzer. Based on the pattern of visual field deficit, the location of the lesion in the mesial occipital lobe in each patient was predicted using the Holmes map and other retinotopic maps of the occipital cortex. The predicted location of the lesion was then compared with its actual location shown on MRI to assess the compatibility between our data and the other maps. These maps determine retinotopic correlates of the medial occipital lobe, but they cannot establish correlates of the striate cortex (V1). The medial occipital representation of central vision was evaluated by regression analysis. The MRI correlations in this study confirmed gross estimates of the retinotopic organization of the occipital cortex. However, our findings did not correlate exactly with the Holmes map. We determined that the central 15 degrees of vision occupies 37% of the total surface area of the human medial occipital lobe. Based on our data, a refined retinotopic map is presented. The resolution of conventional MRI testifies to its considerable value in localizing occipital lobe lesions. Our findings support, and refine, the Holmes map of the human occipital cortex.


The two-way paradigm of transplantation immunology.
The events following organ transplantation require a reciprocal cell interaction which includes both the conventional host-versus-graft reaction and a graft-versus-host component. With all successful transplantation, both graft and recipient become genetic composites. Where donors were available, chimerism has been confirmed in 30-year kidney-recipient survivors, as well as in several liver and lung recipients. A majority of liver recipients have been able to acquire an immunosuppressant-free state after 10-year survival. Animal models suggest that donor-derived cells may exert a tolerogenic effect.


Phosphorylation of the cryptochrome 1 C-terminal tail regulates circadian period length.
The Cryptochrome (CRY) proteins are critical components of the mammalian circadian clock and act to rhythmically repress the activity of the transcriptional activators CLOCK and BMAL1 at the heart of the clock mechanism. The CRY proteins are part of a large repressive complex, the components of which are not completely known. Using mass spectroscopy, we identified the catalytic subunit of DNA-dependent protein kinase as a CRY-interacting protein and found that loss or inhibition of this kinase results in circadian rhythms with abnormally long periods. We then identified serine 588 in the C-terminal tail of mouse CRY1 as a potential DNA-PK phosphorylation site but surprisingly found that the phosphomimetic mutation S588D also results in long period rhythms, similar to the loss of DNA-PK. Consistent with this, we found that phosphorylation of this site is increased in cells lacking DNA-PK, suggesting that DNA-PK negatively regulates the phosphorylation of this site most likely through indirect means. Furthermore, we found that phosphorylation of this site increases the stability of the CRY1 protein and prevents FBXL3-mediated degradation. The phosphorylation of this site is robustly rhythmic in mouse liver nuclei, peaking in the middle of the circadian day at a time when CRY1 levels are declining. Therefore, these data suggest a new role for the C-terminal tail of CRY1 in which phosphorylation rhythmically regulates CRY1 stability and contributes to the proper circadian period length.


Schizosaccharomyces pombe possesses two paralogous valyl-tRNA synthetase genes of mitochondrial origin.
Previous studies showed that VAS1 of Saccharomyces cerevisiae encodes both cytosolic and mitochondrial forms of valyl-tRNA synthetase (ValRS) through alternative initiation of translation. We show herein that except for Schizosaccharomyces pombe, all yeast species studied contained a single ValRS gene encoding both forms, and all of the mature protein forms deduced from those genes possessed an N-terminal appended domain (Ad) that was absent from their bacterial relatives. In contrast, S. pombe contained two distinct nuclear ValRS genes, one encoding the mitochondrial form and the other its cytosolic counterpart. Although the cytosolic form closely resembles other yeast ValRS sequences (approximately 60% identity), the mitochondrial form exhibits significant divergence from others (approximately 35% identity). Both genes are active and essential for the survival of the yeast. Most conspicuously, the mitochondrial form lacks the characteristic Ad. A phylogenetic analysis further suggested that both forms of S. pombe ValRS are of mitochondrial origin, and the mitochondrial form is ancestral to the cytoplasmic form.


Role of binucleate cells in fetomaternal cell fusion at implantation in the sheep.
In the sheep conceptus, individual intraepithelial binucleate cells first appear at 14 days post-coitum (d.p.c.); and by 16 d.p.c. they form 15-20% of the trophectoderm where it is apposed to the caruncular sites of initial attachment to the uterine epithelium. These binucleate cells and their derivatives can be recognized in the placenta by electron microscopy after selective staining of their Golgi body and its products, the numerous characteristic granules. Between 16 and 24 d.p.c. the uterine epithelium transforms to syncytial plaques. Evidence from ultrastructure and serial semithin sections indicates that this transformation is initiated by migration of fetal binucleate cells up to the microvillar junction and their fusion with individual uterine epithelial cells, producing trinucleate fetomaternal hybrid cells. These cells then appear to release their granules to the endometrium. It is suggested that continued binucleate-cell migration and fusion with the trinucleate cells, together with displacement and/or death of the remaining uterine epithelial cells, produces the plaques of syncytium that cover the entire caruncle by 20-24 d.p.c. This caruncular syncytium, in which no nuclear division has been found, expands enormously in area during the formation and maintenance of the cotyledons, deriving its nuclei from binucleate migration.


NMR tensors in planar hydrocarbons of increasing size.
(13)C nuclear shielding and (13)C-(13)C spin-spin coupling tensors were calculated using density functional theory linear response methods for a series of planar hydrocarbons. As calculation of the spin-spin coupling is computationally demanding for large molecules due to demands placed on basis-set quality, novel, compact completeness-optimized (co) basis sets of high quality were employed. To maximize the predictive value of the data, the convergence of the co basis sets was compared to well-known basis-set families. The selection of the exchange-correlation functional was performed based on the available experimental data and coupled-cluster calculations for ethene and benzene. The series of hydrocarbons, benzene, coronene, circumcoronene and circumcircumcoronene, was chosen to simulate increasingly large fragments of carbon nanosheets. It was found that the nuclear shielding and the one-, two-, and three-bond spin-spin coupling constants, as well as the corresponding anisotropies with respect to the direction normal to the plane, approach convergence as the number of carbon atoms in the fragment is increased. Predictions of the investigated properties can then be done for the limit of large planar hydrocarbons or carbon nanosheets. From the results obtained with a judicious choice of the functional, PBE, and co basis close to convergence, limiting values are estimated as follows: sigma = 54 +/- 1 ppm [corresponding to the chemical shift of 134 ppm with methane (CH(4)) as a reference], Deltasigma = 207 +/- 4 ppm, (1)J = 59.0 +/- 0.5 Hz, Delta(1)J = -1.5 +/- 0.5 Hz, (2)J = 0.2 +/- 0.4 Hz, Delta(2)J = -4.6 +/- 0.2 Hz, (3)J = 6 +/- 1 Hz, and Delta(3)J = 3 +/- 1 Hz.


Stimulation of endogenous cyclic AMP levels in ciliary body by SK&F 82526, a novel dopamine receptor agonist.
The effect of dopamine and SK&F 82526 on cyclic AMP metabolism in ocular tissues has been examined. The in vitro incubation of human and bovine ciliary body with these agonists produced a dose-dependent increase in endogenous levels of cyclic AMP. This stimulation was blocked by the selective DA1 receptor antagonist SK&F 83566, but not by the beta-receptor antagonist propranolol. The response to SK&F 82526 was stereoselective, with SK&F R-82526 being approximately 100 times more potent than SK&F S-82526 in this preparation. This stimulation of ciliary body cyclic AMP content was not observed in the rabbit or cat, nor was it seen in human, bovine or rabbit iris tissue. These data suggest that adenylate cyclase linked dopamine receptors are present in both human and bovine ciliary body.


Pseudoginsenoside-F11 attenuates morphine-induced signalling in Chinese hamster ovary-mu cells.
Pseudoginsenoside-F11 (PF11), an ocotillol type saponin isolated from Panax quinquefolium L., has been shown to antagonize the behavioral actions of morphine. Biochemical experiments revealed that PF11 could inhibit diprenorphine (DIP) binding with an IC50 of approximately 6.1 microM and reduced the binding potency of morphine in Chinese hamster ovary (CHO)-mu cells. Furthermore, PF11 significantly attenuated morphine-stimulated [35S]GTPgammaS binding in a dose dependent manner, and strongly decreased the efficacy of morphine to inhibit intracellular cAMP production. In addition, PF11 pretreatment could also significantly inhibit naloxone induced cAMP overshoot in the morphine-pretreated cells. However, PF11 per se had no effect on either [35S]GTPgammaS binding or intracellular cAMP accumulation. These data suggested that PF11 antagonized the morphine stimulated opioid receptor signalling directly at the cellular level.


Effects of spray-dried animal plasma on serous and intestinal redox status and cytokines of neonatal piglets.
The study investigated the effects of dietary supplementation with spray-dried animal plasma (SDAP) on growth performance, intestinal morphology, as well as serum and intestinal cytokines and antioxidant indicators of artificially reared neonatal piglets. Three diets, 1) control (a fish meal basal diet), 2) SDAP (containing 10% SDAP), and 3) autoclaved SDAP (auSDAP; containing 10% auSDAP), were fed to 36 weaned piglets (3 d old), which were randomly allotted to 3 groups. At 21 d of age, blood and intestinal mucosal samples were collected from all piglets after they were slaughtered. Compared with the control, both SDAP and auSDAP improved ADFI and duodenal villus height of piglets (P < 0.05), whereas SDAP increased ADG and duodenal villus height to crypt depth ratio (P < 0.05). Piglets fed SDAP and auSDAP had reduced malondialdehyde (MDA) content in mucosa (P < 0.05). The concentration of serum MDA was decreased and mucosal catalase (CAT) activities were increased in piglets fed SDAP diet than those fed the control diet (P < 0.05). In the mucosa, both SDAP and auSDAP decreased tumor necrosis factor α, IL-6, transforming growth factor β, and soluble IL-2 receptor contents (P < 0.05). Mucosal IL-1β was decreased in SDAP compared with auSDAP and control groups (P < 0.05). The SDAP and control groups had increased mucosal IL-2 compared with auSDAP group (P < 0.05). The cytokines in serum were not affected by SDAP and auSDAP. The results indicate that both SDAP and auSDAP improved the growth performance of neonatal piglets, whereas the SDAP had a greater effect. The benefits of SDAP probably resulted from the promotion of the intestinal development, which were accompanied by the increased antioxidant capacity and the decreased production of inflammatory factors in the intestinal mucosa.


[Time-series analysis on road traffic injury in China].
To establish the predictive models of road traffic injury(RTI) in China, to know the trend of RTI, and to provide the reference data for controlling RTI in China. The China RTI data from 1951 to 2003 were collected, and in view of the problem of missing values, the method of intrapolation was adopted. The Box-Jenkins technique was used to analyze and predict the trend of RTI in China. Following the process for stationary time-series analysis, model identification, parameter estimation and model diagnosis, the predictive equation for RTI would be established. A series of predictive equations on RTI were finally established based on ARIMA models. The curve fitting is effective and the predictive data of RTI in 2003 are close to the true statistical data. The time-series model thus established proves to be of significant usefulness in RTI prediction.


Nitric oxide regulation of corticotropin-releasing hormone release from the human perfused placenta in vitro.
We have investigated the regulatory role of nitric oxide (NO) in corticotropin-releasing hormone (CRH) release from the human perfused placental lobule in vitro. The effects of the NO donor sodium nitroprusside, the NO synthase inhibitor N omega-nitro-L-arginine, and the NO substrate L-arginine on human (h) placental CRH secretion have been studied. Single lobules of term placentae were bilaterally perfused with Krebs solution (5 mL/min; 95% O2-5% CO2; 37 C; pH 7.3). Fetal and maternal perfusates were collected at 4 C every 30 min for 3 h. CRH immunoreactivity (CRH-IR) in perfusates was measured by RIA using the 41-residue synthetic CRH as standard, 125I-labeled Tyr-hCRH as tracer, and a rabbit anti-CRH antibody Y2BO. The sensitivity of the assay was 0.13 pmol/L. Under basal conditions, human perfused placentae in vitro continuously secreted CRH-IR, which diluted in parallel to a synthetic hCRH-(1-41) standard curve. Size-exclusion chromatography of placental perfusates using a Sephadex G-50 column indicated that placental CRH-IR predominately coeluted with hCRH-(1-41) standard. Basal maternal perfusate CRH-IR levels (27 +/- 4 pmol/L) released from perfused placental lobules were nearly 10-fold greater than fetal perfusate CRH-IR levels (3.4 +/- 0.7 pmol/L; P < 0.05). Infusion of sodium nitroprusside (30-100 mumol/L) into the maternal and fetal placental circulations inhibited CRH-IR release into maternal perfusate in a concentration-dependent manner, but did not inhibit CRH-IR release into the fetal perfusate. N omega-nitro-L-arginine (100 mumol/L) increased placental CRH-IR secretion into fetal perfusate, and this effect was reversed by the infusion of L-arginine (100 mumol/L), which also reduced release below basal levels. In contrast, maternal perfusate CRH-IR levels were not affected by N omega-nitro-L-arginine or L-arginine. These results indicate that the human perfused placenta in vitro releases a substance of similar mol wt and hCRH-IR. Moreover, modulators of the NO signaling pathway differentially affect placental secretion of CRH-IR into the maternal and fetal perfusates. These data are consistent with the involvement of NO in the regulation of placental CRH release during pregnancy.


INFLUENCE OF METHOD FOR REMOVAL OF SESTON ON THE DISSOLVED ORGANIC MATTER. II. COBALAMINS.
Comparisons of the 3 previously used methods (continuous flow centrifugation, Millipore®filtration, and biodialysis) for making water samples seston-free before analysis for cobalamins point to several likely sources of error: (a) unpredictable occlusion of pores in Millipore®membranes during filtration; (b) irreversible adsorption of cobalamins by Millipore®membranes; (c) probable cell injury and leakage by centrifugation. Some water samples gave good agreement on soluble vitamin B12 by all 3 methods, while other samples had appreciable discrepancies. The validity of total vs. sestonic cobalamin determinations therefore is questioned. One lake had time-dependent fluctuation in soluble cobalamin.


Disinhibition in risky sexual behavior in men, but not women, during four years of antiretroviral therapy in rural, southwestern Uganda.
In resource-rich areas, risky sexual behavior (RSB) largely diminishes after initiation of anti-retroviral therapy, with notable exceptions among some populations who perceive a protected benefit from anti-retroviral therapy (ART). Yet, there is limited data about long-term trends in risky sexual behavior among HIV-infected people in sub-Saharan Africa after initiation of anti-retroviral therapy. We administered questionnaires every three months to collect sexual behavior data among patients taking ART in southwestern Uganda over four years of follow-up time. We defined RSB as having unprotected sex with an HIV-negative or unknown status partner, or unprotected sex with a casual partner. We fit logistic regression models to estimate changes in RSB by time on ART, with and without adjustment for calendar year and CD4 count. 506 participants were enrolled between 2005 and 2011 and contributed a median of 13 visits and 3.5 years of observation time. The majority were female (70%) and median age was 34 years (interquartile range 29-39). There was a decrease in the proportion of men reporting RSB from the pre-ART visit to the first post-ART visit (16.2 to 4.3%, p<0.01) but not women (14.1 to 13.3%, p = 0.80). With each year of ART, women reported decreasing RSB (OR 0.85 per year, 95%CI 0.74-0.98, p = 0.03). In contrast, men had increasing odds of reporting RSB with each year of ART to near pre-treatment rates (OR 1.41, 95%CI 1.14-1.74, p = 0.001), which was partially confounded by changes in calendar time and CD4 count (AOR = 1.24, 95%CI 0.92-1.67, p = 0.16). Men in southwestern Uganda reported increasing RSB over four years on ART, to levels approaching pre-treatment rates. Strategies to promote long-term safe sex practices targeted to HIV-infected men on ART might have a significant impact on preventing HIV transmission in this setting.


Laser labyrinthectomy in humans.
This paper describes the feasibility of labyrinthectomy of only the vestibular part using argon laser in humans. In animal experiments, the utricular and saccular maculae were completely destroyed using argon laser with the otoprobe of the HGM system via the oval window, following stapedectomy. The human utricular and saccular maculae can be approached in a similar manner. Several approaches to the nerves and ampullae of the anterior and lateral semicircular canals are discussed. The most appropriate method to abolish the function of the ampullae is to sever the ampullary nerves. This can be done through the widened oval window with the argon laser otoprobe. After laser application, the oval window is covered by a piece of perichondrium. A stapes prosthesis is placed on the long process of the incus. Laser singular neurectomy may be used to sever the nerve to the posterior ampulla.


Remission of HPV infection after LEEP-conization - a retrospective study.
Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases. Long-term exposure to the HPV is a known cause of squamous intraepithelial lesions that consequently lead to cervical cancer development. The loop electrosurgical excision procedure (LEEP) conization is an established early cervical cancer treatment method. We aim to assess the remission of HPV infection after LEEP in non-vaccinated patients with pre-cancerous cervical lesions and establish the efficacy of cervical cancer prophylaxis. We analyzed 31 LEEP conizations performed due to low and high-grade squamous intraepithelial lesions in 2019-2020. We obtained molecular test samples and detected DNA of 37 different HPV genotypes. After a six-month follow-up, each patient underwent subsequent high-risk HPV testing and genotyping. We observed that 54.8% of qualified patients were infected with HPV 16. We discovered complete viral remission in 64.5% of cases. After surgery, margins were negative in 71% of the patient's samples. During the follow-up, six patients got infected with new strains of HPV. We found that a correctly performed LEEP conization may contribute to the remission of persistent HPV infection; a more extended follow-up period might be recommended due to a high rate of post-surgery HPV infections.


Maternal responses to daily maternal porcine somatotropin injections during early-mid pregnancy or early-late pregnancy in sows and gilts.
Piglet neonatal survival and postnatal growth and efficiency are positively related to birth weight. In gilts, daily maternal porcine ST (pST) injections from d 25 to 100 (term approximately 115 d), but not d 25 to 50, of pregnancy increase progeny birth weight. Daily maternal pST injections from d 25 to 50 increase fetal weight at d 50 in gilts and sows. We therefore hypothesized that daily pST injections from d 25 to 100, but not d 25 to 50, of pregnancy would increase birth weight similarly in both parities. Landrace x Large White gilts and sows were uninjected (controls) or were injected daily with pST (gilts: 2.5 mg/d; sows: 4.0 mg/d, each approximately 15 microg of pST/kg per day) from d 25 to 50 or 100 of pregnancy. Litter size and BW were recorded at birth, midlactation, and weaning. Dams were followed through the subsequent mating and pregnancy. Maternal pST injections from d 25 to 100, but not d 25 to 50, increased mean piglet birth weight by 11.6% in sows (P <or= 0.001) and by 5.6% in gilts (P = 0.008). Both pST treatments decreased litter size by approximately 0.6 live-born piglets (each P <or= 0.025). In sows, maternal pST treatment from d 25 to 100 increased culls at weaning (P = 0.037). In remated dams, prior treatments did not affect (P > 0.1) the weaning-remating interval, conception rate, or subsequent litter size. Greater pST-induced birth weight increases in sows than in gilts may mean that underlying metabolic or placental mechanisms for pST action are constrained by maternal competition for nutrients in rapidly growing gilts.


Evaluation of Glyde File Prep in combination with sodium hypochlorite as a root canal irrigant.
The purpose of this study using a scanning electron microscope was to investigate the efficacy of four different irrigation techniques after canal preparation with Profile Ni-Ti rotary instruments. A modified technique for the use of Glyde File Prep is proposed. Forty anterior teeth were divided into four groups, instrumented, and irrigated as follows: physiological solution (group A), 2.5% sodium hypochlorite (group B), 2.5% sodium hypochlorite and Glyde File Prep (group C), and 2.5% sodium hypochlorite and Glyde File Prep applied at the end of the preparation with sterile paper points (group D). After scanning electron microscopic evaluation at three different levels, debris, smear layer, and dentinal tubules were scored. Groups A and B had significantly more smear layer and less open tubules on the canal walls compared with the group C and group D samples. Differences in the mean amount of debris between group A samples and other irrigation regimes were statistically significant.


Hemodynamic characteristics of a mixed flow pump prototype: progress report of in vitro and acute animal experiments.
A new dual-inlet mixed-flow blood pump was designed and tested in our laboratory. The objective of the present study was to analyze hemodynamic characteristics of the pump prototype in vitro and during acute in vivo experiments. The mixed-flow pump was first tested in vitro and then implanted in 11 pigs and 3 calves. The left ventricular apex was cannulated with the pump and an outflow graft was anastomosed to the descending thoracic aorta. Flow and pressure probes were also implanted. Animals were killed 3 to 12 hours after surgery. In 11 pigs, pump outflow averaged 3.8 +/- 0.4, 4.5 +/- 0.4, 5.2 +/- 0.8, 5.9 +/- 0.3, and 6.5 l/min at 8,000, 9,000, 10,000, 11,000, and 12,000 pump speed in rpm. Differential pressure at the pump averaged 45 +/- 6, 54 +/- 8, 68 +/- 16, 70 +/- 12, and 85 +/- 7 mm Hg at 8,000, 9,000, 10,000, 11,000 and 12,000 rpm. Mean aortic pressure averaged 64 +/- 15 mm Hg throughout the procedures. In 3 calves, mean aortic pressure and left ventricular pressure remained stable during 4, 6, and 9 hours of support at 9,500, 10,000, 10,500, 11,000, and 11,500 rpm. The hemodynamic performance of our mixed-flow pump appears satisfactory during short-term support in animals. It supports similarly to axial-flow blood pumps in clinical trials. Based on these findings, an ameliorated design of this mixed-flow pump running at smaller rotational speed against a similar pressure head is under way.


Outcomes in severely ill patients transported without prehospital ALS.
Because of the debate regarding the impact of advanced life support (ALS) care on the outcome of prehospital patients, we monitored the influence of lack of sophisticated prehospital treatment in cases of severe illness arriving by ambulance to the emergency department (ED). A prospective cohort study to examine and compare the outcome of trauma- and nontrauma-induced "ALS-eligible" cases in the setting of no prehospital care was carried out from August 1, 1993 through May 31, 1994. On arriving at the ED, patients meeting the criteria for ALS cases and sent by EMS public prehospital personnel were assessed for subjective and objective status and change in severity by triage nurses as well as being followed up for neurological status until discharged from the hospital. Chi-Square method was used to compare the data between two groups and P < .05 was considered statistically significant. Of 667 studied ALS cases (155 trauma and 512 nontrauma), < 20% had their condition change subjectively and < 10% had their condition change objectively; 68% of medical patients and 60% of trauma cases were discharged from the hospital (neurologically intact). However, subgroup analysis showed that objective measures worsened in transit in nearly 18% of trauma victims, a rate nearly 3 times greater than that of medical cases. Moreover, neurological outcome was particularly poor in trauma cases. These results suggest that ALS care may be valuable for severely ill trauma victims.


An uncommon association of abdominal vascular compression syndromes: Dumbar and Nutcracker.
Abdominal pain associated with nausea and vomiting in a young patient led to a diagnosis of median arcuate ligament syndrome. The presence of mild haematuria was associated with a concomitant Nutcracker syndrome. Diagnosis was achieved by a computed tomography scan, which showed compression of the vessels of the coeliac axis and left renal vein. These syndromes are very rare, and their association in the same patient has not been described before. There is no relationship in the aetiology of these entities. In this report we discuss the diagnosis and therapeutic options, and review the literature.


[Pathology of the placenta. V. Circulatory disorders of the placenta. Fetal vascular system].
Discussed are circulatory disorders as well as pathologico-anatomic findings recordable from fetal vessels of the placenta. Thorough reference is first made to obliterative endoarteritis of the greater arteries. Its forms are described, with formal and causative pathogenesis being discussed. Conclusive coverage of causative pathogenesis has proved to be possible only for unambiguously determined inflammatory manifestations (rubella, lues). The second major complex covers alterations to greater and minor fetal vessels which are characterized by central parietal thrombosis (possibly associated with fetal asphyxia) and peripherally disseminated intravasal coagulation (associated with peripartal shock or other conditions). Included in the latter group of alterations are congenital pulmonary hyaline membranes (perhaps also some membranes of postnatal origin) which are, as well, considered as shock equivalent.


RNA polymerase II trigger loop residues stabilize and position the incoming nucleotide triphosphate in transcription.
A structurally conserved element, the trigger loop, has been suggested to play a key role in substrate selection and catalysis of RNA polymerase II (pol II) transcription elongation. Recently resolved X-ray structures showed that the trigger loop forms direct interactions with the beta-phosphate and base of the matched nucleotide triphosphate (NTP) through residues His1085 and Leu1081, respectively. In order to understand the role of these two critical residues in stabilizing active site conformation in the dynamic complex, we performed all-atom molecular dynamics simulations of the wild-type pol II elongation complex and its mutants in explicit solvent. In the wild-type complex, we found that the trigger loop is stabilized in the "closed" conformation, and His1085 forms a stable interaction with the NTP. Simulations of point mutations of His1085 are shown to affect this interaction; simulations of alternative protonation states, which are inaccessible through experiment, indicate that only the protonated form is able to stabilize the His1085-NTP interaction. Another trigger loop residue, Leu1081, stabilizes the incoming nucleotide position through interaction with the nucleotide base. Our simulations of this Leu mutant suggest a three-component mechanism for correctly positioning the incoming NTP in which (i) hydrophobic contact through Leu1081, (ii) base stacking, and (iii) base pairing work together to minimize the motion of the incoming NTP base. These results complement experimental observations and provide insight into the role of the trigger loop on transcription fidelity.


Relationship between religion and redress relief among Japanese American World War II incarceration survivors.
Soon after Japan attacked Pearl Harbor and the United States entered World War II, more than 110,000 Japanese Americans (two-thirds U.S. citizens) were rounded up and ordered into desolate incarceration (internment) camps based only on their ethnic heritage. More than 40 years later, the U.S. government acknowledged that the Japanese American incarceration was unjustified and provided a formal apology and monetary award to surviving incarcerees. The present study investigates the relationship between religious affiliation (Buddhist and Christian) and subsequent perceptions of relief associated with the government's belated redress. Based on a national sample of U.S.-born Japanese American former incarcerees (N = 454), Buddhist incarcerees reported greater relief from receiving redress than Christians. Across religious affiliations, older incarcerees and those with lower income reported more relief. Both Buddhist and Christian respondents who perceived more Japanese American incarceration-related physical suffering, and those who believed in a just world, experienced greater relief. In addition, Buddhists who more strongly believed their lives are controlled by unpredictable fate/fortune, and Christians who more strongly believed their lives were controlled by powerful others experienced greater redress relief. Findings suggest the role of religious frameworks in shaping the restorative capacity of belated reparative acts following historical racial trauma. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Retinoids induce antagonism between FOXO3A and FOXM1 transcription factors in human oral squamous cell carcinoma (OSCC) cells.
To gain a greater understanding of oral squamous cell carcinoma (OSCC) we investigated the actions of all-trans-retinoic acid (RA; a retinoid), bexarotene (a pan-RXR agonist), and forkhead box (FOX) transcription factors in human OSCC-derived cell lines. RA and bexarotene have been shown to limit several oncogenic pathways in many cell types. FOXO proteins typically are associated with tumor suppressive activities, whereas FOXM1 acts as an oncogene when overexpressed in several cancers. RA and/or bexarotene increased the transcript levels of FOXO1, FOXO3A, and TRAIL receptors; reduced the transcript levels of FOXM1, Aurora kinase B (AURKB), and vascular endothelial growth factor A (VEGFA); and decreased the proliferation of OSCC-derived cell lines. Also, RA and/or bexarotene influenced the recruitment of FOXO3A and FOXM1 to target genes. Additionally, FOXM1 depletion reduced cell proliferation, decreased transcript levels of downstream targets of FOXM1, and increased transcript levels of TRAIL receptors. Overexpression of FOXO3A decreased proliferation and increased binding of histone deacetylases (HDACs) 1 and 2 at the FOXM1, AURKB, and VEGFA promoters. This research suggests novel influences of the drugs RA and bexarotene on the expression of FOXM1 and FOXO3A in transcriptional regulatory pathways of human OSCC.


Genome-Wide Analysis of Glycoside Hydrolase Family 1 β-glucosidase Genes in Brassica rapa and Their Potential Role in Pollen Development.
Glycoside hydrolase family 1 (GH1) β-glucosidases (BGLUs) are encoded by a large number of genes, and are involved in many developmental processes and stress responses in plants. Due to their importance in plant growth and development, genome-wide analyses have been conducted in model plants (Arabidopsis and rice) and maize, but not in Brassica species, which are important vegetable crops. In this study, we systematically analyzed B. rapa BGLUs (BrBGLUs), and demonstrated the involvement of several genes in pollen development. Sixty-four BrBGLUs were identified in Brassica databases, which were anchored onto 10 chromosomes, with 10 tandem duplications. Phylogenetic analysis revealed that 64 genes were classified into 10 subgroups, and each subgroup had relatively conserved intron/exon structures. Clustering with Arabidopsis BGLUs (AtBGLUs) facilitated the identification of several important subgroups for flavonoid metabolism, the production of glucosinolates, the regulation of abscisic acid (ABA) levels, and other defense-related compounds. At least six BrBGLUs might be involved in pollen development. The expression of BrBGLU10/AtBGLU20, the analysis of co-expressed genes, and the examination of knocked down Arabidopsis plants strongly suggests that BrBGLU10/AtBGLU20 has an indispensable function in pollen development. The results that are obtained from this study may provide valuable information for the further understanding of β-glucosidase function and Brassica breeding, for nutraceuticals-rich Brassica crops.


[Operative technique and follow-up effect of endoscopic congenital choanal atresia and dilatation].
Objective:To discuss the operative technique and follow-up effect of endoscopic dilatation and plasty for congenital choanal atresia in infants. Method:Clinical data of 7 children with congenital choanal atresia operative treatmented during September 2016 to January 2018 were analyzed retrospectively. the follow-up were followed closely and analyz the operative effect. Result: Seven cases were diagnosed by electronic nasopharyngoscope, nasal CT confirm the nature of atresia plate, and all 7 case successfully complete the operation. Follow-up survey ranged from 8 months to 23 months, postoperative nasal ventilation is good. The first case of bilateral choanal atresia was removed the nasal stenting after operative 3 months, and founded stenosis 1 month later. Reoperation to enlarge the choanal and retained the nasal stenting for 6 months, no restenosis or atresia after 15 months of follow-up. One patient gave up further treatment because of his own reasons and was lost to follow-up. The other 5 cases had no obvious constriction, good ventilation and no operative complications.Conclusion:Electronic nasopharyngoscope is noninvasive, convenient and accurate in the diagnosis of choanal atresia. Nasal CT confirm the nature of the atresia plate. Endoscopic dilatation and plasty of choanal atresia should be retained the nasal stenting for more than 6 months, avoid re-constriction. .


The predatory mite Phytoseiulus persimilis adjusts patch-leaving to own and progeny prey needs.
Integration of optimal foraging and optimal oviposition theories suggests that predator females should adjust patch leaving to own and progeny prey needs to maximize current and future reproductive success. We tested this hypothesis in the predatory mite Phytoseiulus persimilis and its patchily distributed prey, the two-spotted spider mite Tetranychus urticae. In three separate experiments we assessed (1) the minimum number of prey needed to complete juvenile development, (2) the minimum number of prey needed to produce an egg, and (3) the ratio between eggs laid and spider mites left when a gravid P. persimilis female leaves a patch. Experiments (1) and (2) were the pre-requirements to assess the fitness costs associated with staying or leaving a prey patch. Immature P. persimilis needed at least 7 and on average 14+/-3.6 (SD) T. urticae eggs to reach adulthood. Gravid females needed at least 5 and on average 8.5+/-3.1 (SD) T. urticae eggs to produce an egg. Most females left the initial patch before spider mite extinction, leaving prey for progeny to develop to adulthood. Females placed in a low density patch left 5.6+/-6.1 (SD) eggs per egg laid, whereas those placed in a high density patch left 15.8+/-13.7 (SD) eggs per egg laid. The three experiments in concert suggest that gravid P. persimilis females are able to balance the trade off between optimal foraging and optimal oviposition and adjust patch-leaving to own and progeny prey needs.


Communication tips for clinical engineering.
Regular communication between the clinical engineering department and the wider hospital community not only keeps other departments informed about CE activities, but also conveys the value that CE brings to the institution. We provide a list of topics and information that CE should consider conveying to various groups within the hospital.


Occupational hazards to health care workers: report of a conference.
Health care workers are exposed to an array of physical, chemical, biological, and psychosocial hazards. At a national conference in Seattle May 11-13, 1983, hospital occupational medicine programs were characterized as lagging far behind those in industries with comparable illness and injury rates. Participants and speakers recommended that health care workers be trained to recognize occupational hazards; that epidemiologic, laboratory, and clinical studies be undertaken to discern trends and establish the mechanisms of effects from hazardous exposures; and that adequate employee health and safety programs be established in health care settings.


The role of glucagon- and somatostatin-secreting cells in the regulation of insulin release and beta-cell function in heterotypic pseudoislets.
Pseudoislet studies have concentrated on single beta-cell lines or a combination of insulin and glucagon-secreting cells, overlooking the potential role of somatostatin in insulin release. This study sought to evaluate a heterotypic pseudoislet model containing insulin- (MIN6), glucagon- (αTC1.9) and somatostatin (TGP52)-secreting cells of mouse origin and to compare these pseudoislets with traditional monolayer preparations. Cellular viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase assays), proliferation (5-bromo-2-deoxyuridine ELISA), hormone content and functional insulin release in response to a variety of stimuli were measured. Differential expression of E-cadherin, connexin 36 and connexin 43 was assessed by reverse transcriptase-polymerase chain reaction and Western blot to determine a possible role for adherens in insulin release from these pseudoislets. All pseudoislet cells displayed reduced proliferation coupled with an increase in cell death which may contribute to their static size in culture. While MIN6 and TGP52 cells expressed E-cadherin and showed sustained or improved hormone content when configured as pseudoislets, αTC1.9 lacked E-cadherin and contained less glucagon following pseudoislet formation. MIN6 and αTC1.9 cells expressed connexin 36, but not connexin 43 and TGP52 cells expressed connexin 43 only. In the presence of Alanine, Arginine and glucagon-like peptide-1, heterotypic pseudoislet cultures secreted levels of insulin that were comparable to that of MIN6 pseudoislets. In addition, pseudoislets comprising all three cell lines released more insulin into the surrounding culture medium than MIN6 pseudoislets when studied over a 1-week period. The current model may prove useful in studying the role of islet cell interactions in the release of insulin from pancreatic islets.


Unravelling Rashba-Dresselhaus Splitting Assisted Magneto-Photoelectrochemical Water Splitting in Asymmetric MoSSe-GaN Heterostructures.
Among two-dimensional (2D) materials, asymmetric Janus structures (MoSSe, WSSe) have many exciting properties, such as out-of-plane piezoelectricity, spatial isolation of charge carriers, and strong spin-orbit coupling (SOC), resulting in a significant Rashba effect. However, the experimental validation to utilize SOC along with advanced optical properties for catalytic applications remains unexplored. Herein, for the first time, we demonstrate a proof-of-concept for spin-manipulated photo-electrochemical water splitting using Janus MoSSe/GaN heterostructures under an external low magnetic field. Further, the activation with delaminated 2D-MXene (Ti3C2Tx/MoSSe/GaN) for efficient electron channeling manifests ∼1.37 times photocurrent enhancement and ∼1.50-fold enhancement in product (H2/O2) formation under a low applied magnetic field (0.4 T). The external magnetic field supports spin manipulation even under unpolarized light by a spin-to-charge conversion in Janus MoSSe/GaN heterostructures. Density functional theory simulations were performed to understand the role of the Rashba-Dresselhaus effect for efficient charge transport.


Sodium tanshinone IIA sulfonate inhibits porcine reproductive and respiratory syndrome virus via suppressing N gene expression and blocking virus-induced apoptosis.
Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic loss in the swine industry. Currently, there is no effective way to prevent PRRSV infection. Sodium tanshinone IIA sulfonate (STS), a natural compound derived from Salvia miltiorrhiza, was shown to possess anti-PRRSV activity, but the underlying mechanisms remain unclear. The objective of this study was to investigate the effect of STS on PRRSV-induced cell apoptosis and PRRSV N protein expression pattern. Relative quantification real-time PCR was used to evaluate the inhibition of STS on N gene expression. Simultaneously indirect immunofluorescence assay (IFA) and western blot were used to assess the effect on N protein expression. Apoptosis was analysed using fluorescence microscope with an annexin V-EGFP kit. The effect of STS on caspase-3 cleaving was assessed by western blot. Our results showed that STS could inhibit viral N gene expression at both the messenger RNA stage and at the protein level in PRRSV-infected cells in a dose-dependent manner. In addition, STS could also rescue PRRSV-induced apoptosis. Our data suggest that STS may serve as a base compound for developing more effective drugs against PRRSV infection.


[Senolytics against Covid-19?]
The elimination of some senescent cells by « senolytic » compounds can greatly improve the health of aged mice and in some cases reverse the effects of aging. Using a microbial exposure system that closely models coronavirus infection, it is possible to largely protect old mice from the effects of viral infection. This immediately suggests clinical application of the approach, and is the aim of ongoing phase II clinical trials in Covid-19 patients.


Simultaneous bilateral tubal pregnancy after intracytoplasmic sperm injection.
Since the advent of assisted reproductive technology, the concern about ectopic implantation of embryos has increased dramatically. Simultaneous bilateral tubal pregnancy is the least common type of ectopic implantation of two embryos. In this report we present the first case of simultaneous bilateral tubal pregnancy after intracytoplasmic sperm injection (ICSI) and embryo transfer treatment. The present case had no risk factor for ectopic pregnancy. Therefore, for early diagnosis and management of such cases, close clinical follow-up and routine ultrasonography following ICSI are necessary.


The Impact of Cognitive Load on the Cardiac Orienting Response to Auditory Structural Features during Natural Radio Listening Situations.
Previous research has shown that structural features such as voice changes, jingle onsets, and production effects in a radio broadcast elicit cardiac orienting responses. In fact, the voice change has been shown to reliably elicit orienting without habituation after several repetitions. However, repeated onsets of two other auditory structural features-jingles and production effects-did result in habituation when the participant was exposed to them embedded in an audio production absent a central cognitive task. This article presents two experiments testing the possibility that adding a central task prevents the development of a robust neural model of the auditory structural features necessary for habituation. In both studies, results show that adding a primary cognitive task eliminated habituation to jingles and production effects. However, varying the cognitive load of the primary task across two levels of difficulty had no significant effect on habituation.


The sensor kinase KdpD of Escherichia coli senses external K+.
The Kdp system of Escherichia coli is composed of the high-affinity K(+) transporter KdpFABC and the two regulatory proteins KdpD (sensor kinase) and KdpE (response regulator), which constitute a typical two-component system. The kdpFABC operon is induced under K(+) -limiting conditions and, to a lesser extent, under high osmolality in the medium. In search for the stimulus sensed by KdpD, we studied the inhibitory effect of extracellular K(+) on the Kdp system at pH 6.0, which is masked by unspecific K(+) transport at higher pH values. Based on KdpD derivatives carrying single aspartate replacements in the periplasmic loops which are part of the input domain, we concluded that the inhibition of the Kdp system at extracellular K(+) concentrations above 5 mM is mediated via KdpD/KdpE and not due to inhibition of the K(+) -transporting KdpFABC complex. Furthermore, time-course analyses of kdpFABC expression revealed that a decline in the extracellular K(+) concentration efficiently stimulates KdpD/KdpE-mediated signal transduction. In this report we provide evidence that the extracellular K(+) concentration serves as one of the stimuli sensed by KdpD.


Non-Cytotoxic Crosslinkers for Heart Valve Tissue Engineering.
Currently, no effective crosslinking reagents are available to treat xenogenic decellularized heart valve matrices. The study aim was to evaluate the crosslinking effect of quercetin, catechin, caffeic acid and tannic acid on porcine aortic valve matrices. Cytotoxicity of the different crosslinkers was evaluated. The mechanical properties of crosslinked porcine matrices and control matrices (non-fixed) were examined by tensile strength testing, as was the cytocompatibility of the fixed matrices. Crosslinked and control matrices were implanted subcutaneously in Wistar rats (n = 9) and, after two weeks, their calcium contents were determined using inductively coupled plasma-mass spectrometry. The antibody reaction against porcine tissue in rat serum was also determined. Cytotoxicity studies showed that crosslinkers, even at high concentrations, did not inhibit cell viability. All crosslinkers except tannic acid improved the mechanical strength of acellular porcine matrices. Moreover, the tensile strength of quercetin-fixed matrices was comparable with that of glutaraldehyde (GTA)-fixed leaflets. Light microscopic evaluation showed that crosslinked matrices caused only a mild lymphocytic inflammatory reaction. Furthermore, quercetin-fixed leaflets exhibited a well-preserved matrix without infiltration of CD3+ cells. After two weeks, calcium levels were 206.33 µg/mg for controls (non-fixed), and 151.33 µg/mg, 181 µg/mg and 163.66 µg/mg for quercetin-, catechin-, and caffeic acid-fixed matrices, respectively. At two weeks after implantation the quercetin-crosslinked matrices also elicited the lowest levels of IgG antibodies. The study results identified quercetin as the most suitable crosslinker for heart valve tissue engineering, and a possible alternative to GTA. Further studies are essential to determine whether quercetin crosslinking will allow autologous cell repopulation in order to create a viable heart valve.


Partial molecular cloning of the JHK retrovirus using gammaretrovirus consensus PCR primers.
The JHK virus (JHKV) was previously described as a type C retrovirus that has some distinctive ultrastructural features and replicates constitutively in a human B-lymphoblastoid cell line, JHK-3. In order to facilitate the cloning of sequences from JHKV, a series of partially degenerate consensus retroviral PCR primers were created by a data-driven design approach based on an alignment of 14 diverse gammaretroviral genomes. These primers were used in the PCR amplification of purified JHK virion cDNA, and ana lysis of the resulting amplified sequence indicates that the JHKV is in the murine leukemia virus (MLV) family. The JHK sequence is nearly identical to the corresponding region of the Bxv-1 endogenous mouse retrovirus (GenBank accession AC115959) and distinct from XMRV. JHKV gag-specific amplification was demonstrated with nucleic acids from uncultivated, frozen, peripheral blood mononuclear cells (PBMCs) of the index patient, but not in PBMCs from nine healthy blood donors. Unlike earlier reports, in which MLV-like sequences were identified in human source material, which may have been due to murine contamination, budding retrovirions were demonstrated repeatedly by electron microscopy in uncultivated lymphocytes of the index patient that were morphologically identical in their development to the virions in the JHK-3 cells, and immunological evidence was obtained that the index patient produced IgG antibodies that bound to the budding viral particles in patient PBMCs and in the JHK-3 cells. These data indicate that the patient had been infected by JHKV, lending significance to the demonstration of JHKV amplicons in nucleic acids of the patient's PBMCs. In future studies, the PCR primer sets described herein may expand the detection of an amplifiable subset of viruses related to MLV.


Immobilization and Evaluation of Penicillin G Acylase on Hydroxy and Aldehyde Functionalized Magnetic α-Fe2O3/Fe3O4 Heterostructure Nanosheets.
Magnetic α-Fe2O3/Fe3O4 heterostructure nanosheets were fabricated via hydrothermal calcination. The activity of penicillin G acylase (PGA), which was covalently immobilized onto silica-decorated heterostructure nanosheets, achieved the highest activity of 387.03 IU/g after 18 h of incubation with 0.1 ml of PGA. In contrast, the activity of free PGA reached the highest level when the temperature was 45°C with a pH of 8.0. However, the activity of free PGA changed more dramatically than immobilized PGA as the relative conditions changed. Moreover, the Michaelis-Menten constant (Km) and reusability of immobilized PGA were also explored. The results showed that free PGA Km and maximum rate (Vmax) were 0.0274 M and 1.167 μl/min, respectively. Km and Vmax values of immobilized PGA were 0.1082 M and 1.294 μl/min, respectively. After 12 cycles of repetitive use, immobilized PGA remained approximately 66% of its initial activity, indicating that the PGA immobilized onto the heterostructure nanosheets showed better stability and reusability than free PGA.


Observance of ethical codes in selecting supervisor by postgraduate students.
Nowadays, with development of medical sciences, several ethical challenges have raised which make research more complicated. Observance of student's right in selecting interested research topic and the supervisor, in addition to its positive effect on the research process, will cause satisfaction and quality promotion in the educational system. To observe that issue, during a confidential survey of a number of postgraduate students in 2009, students were asked to confidentially describe any displeasure they might get during their study and research. The most important items included: imposing thesis by a supervisor without informing the student, compulsory assignment of students to a specific supervisor, little time allocated for students by the supervising team who may be selected without students interests, prolongation of the research time, and non-cooperation in publishing the results. Establishment of a proper way to transfer student's displeasure or criticism to supervisors and establishing a continuous program for informing research teams including supervisors and students about ethical codes can positively affect the issue.


Local rigidity in sandpile models.
We address the problem of the role of the concept of local rigidity in the family of sandpile systems. We define rigidity as the ratio between the critical energy and the amplitude of the external perturbation and we show, in the framework of the dynamically driven renormalization group, that any finite value of the rigidity in a generalized sandpile model renormalizes to an infinite value at the fixed point, i.e., on a large scale. The fixed-point value of the rigidity allows then for a nonambiguous distinction between sandpilelike systems and diffusive systems. Numerical simulations support our analytical results.


Geniposide alleviates lipopolysaccharide-caused apoptosis of murine kidney podocytes by activating Ras/Raf/MEK/ERK-mediated cell autophagy.
Proteinuria is one of the most important clinical features of nephrotic syndrome (NS). Injury of podocyte has been proved to contribute to the occurrence of proteinuria. This study explored the effects of geniposide (GEN) on lipopolysaccharide (LPS)-caused murine kidney podocyte MPC5 apoptosis and autophagy. Viability and apoptosis of MPC5 cells were respectively detected with the help of CCK-8 assay and Guava Nexin assay. 3-Methyladenine (3-MA) was used as an autophagy inhibitor, while rapamycin as autophagy activator. Si-Beclin-1 was transfected in MPC5 cells to down-regulate the expression of Beclin-1. We found that LPS stimulation significantly caused MPC5 cell viability reduction, apoptosis and autophagy (P < .05 or P < .01). GEN treatment remarkably alleviated the LPS-caused MPC5 cell viability reduction and apoptosis, but promoted cell autophagy (P < .05). Moreover, 3-MA incubation or si-Beclin-1 transfection notably weakened the effects of GEN on LPS-caused MPC5 cell apoptosis and autophagy (P < .05), while rapamycin had opposite effects (P < .05). Furthermore, GEN activated Ras/Raf/MEK/ERK pathway in LPS-treated MPC5 cells (P < .05). In conclusion, this research verified the protective effects of GEN on podocytes damage. GEN alleviates LPS-caused apoptosis of murine kidney podocytes by activating Ras/Raf/MEK/ERK-mediated cell autophagy. Highlights: LPS causes podocyte MPC5 apoptosis and autophagy. GEN alleviates LPS-caused MPC5 cell apoptosis, but promotes cell autophagy. 3-MA or si-Beclin-1 weakens the effects of GEN on LPS-treated MPC5 cells. Rapamycin strengthens the effects of GEN on LPS-treated MPC5 cells. GEN activates Ras/Raf/MEK/ERK pathway in LPS-treated MPC5 cells.


Induction of urinary plasminogen activator by retinoic acid results in increased invasiveness of human prostate cancer cells PC-3.
Overproduction of uPA by prostate cancer cells in vivo results in tumor invasiveness and osteoblastic skeletal metastasis due to its mitogenic actions in osteoblasts. In the present study we have examined the effect of several growth factors and steroid hormones on regulating uPA gene expression in the human prostate cancer cell line (PC-3). Treatment of these cells with dexamethasone (Dex) caused a decrease, whereas epidermal growth factor (EGF) and fetal bovine serum (FBS) increased uPA expression in a dose-dependent manner. Trans retinoic acid (RA) also induced uPA mRNA and protein production in a dose-dependent manner (10(-6) to 10(-9) M). This increase was seen as early as 2 hr of treatment until 48 hr. Dex treatment resulted in decreased tumor cells invasiveness, whereas exposure to EGF and RA caused an increase in the invasive capacity of PC-3 cells. These studies should help to better understand the control mechanism of uPA expression in prostate cancer, where uPA has been implicated as a major pathogenetic factor.


Calcifying fibrous pseudotumor of the adrenal gland: A rare case report.
Calcifying fibrous pseudotumor (CFP) is a rare benign soft tissue lesion. We herein present an extremely rare case of CFP of the adrenal gland. A 32-year-old male patient presented to our hospital with a tumor-like lesion in the area of the left adrenal gland detected by ultrasound during a routine check-up several days prior. Contrast-enhanced magnetic resonance imaging examination revealed a solitary, well-circumscribed mass, in close proximity to the medial arterial branch of the left adrenal gland. Histological examination revealed that the tumor consisted of sheets of varying amount of inflammatory cell infiltration; interstitial fibrosis and psammomatous calcifications were also observed. To the best of our knowledge, this is the third case of CFP occurring in the adrenal gland in the published literature. We herein report the findings of this case and review the two previously reported cases of CFP of the adrenal gland with valuable information.