Continued Growth of the Femoral Neck Leads to Improved Remodeling After In Situ Fixation of Slipped Capital Femoral Epiphysis.
Globally, the most common method for in situ fixation of slipped capital femoral epiphysis (SCFE) is a threaded screw, which causes physeal arrest. The standard treatment in Sweden is unthreaded fixation using the Hansson hook-pin, which leads to continued growth of the femoral neck. Our purpose was to study remodeling during the remaining growth after fixation with the Hansson hook-pin. We performed a retrospective study of 54 patients with SCFE who were treated with the Hansson hook-pin between 2001 and 2009. The immediate postoperative radiograph and the radiograph taken after physeal closure (mean interval, 34 mo) were analyzed. Three radiographic assessments were used: the head-shaft angle (HSA), the alpha angle (Nötzli), and the displacement from Klein's line. Significant remodeling was detected in all measured parameters. The mean postoperative HSA decreased by 9.0 degrees (P<0.001). The alpha angle improved by a mean of 14.5 degrees (P<0.001). Significant correlations were found between the reduction of the alpha angle and age (P<0.001, R=0.48) and longitudinal growth of the femoral neck (P<0.001, R=0.67). Displacement from Klein's line increased by a mean of 1.6 mm (P=0.006). Unthreaded fixation of SCFE using the Hansson hook-pin leads to substantial remodeling of the femoral neck. The positive correlation observed between the improvement of the alpha angle and femoral neck growth supports the use of a method that allows continuous growth, to reduce the risk of femoroacetabular impingement. Level III-retrospective comparative study.


Changes in quality of life after rehabilitation for patients with progressive neurological disorders.
The aim was to study whether patients with progressive neurological disorders experienced a changed quality of life at the end of a rehabilitation period and 3-4 months after their return home. Forty-one and 37 patients respectively filled in a self-administered questionnaire Quality of Life: Status and Change (QLsc). There was a significant difference between the two occasions for responses regarding the items 'My bodily health has become', 'My well-being has become' and 'I am able to maintain a good pace and lead an active life'. The alternatives 'rather good' to 'much better' were chosen more often at the end of the rehabilitation period than after 3-4 months. There were also differences between respondents who had been to the rehabilitation centre for the first time and those who had recurrent visits, regarding the items: 'My bodily health has become', 'My well-being has become' and 'My whole life is'. The alternative neither/nor was rated fairly evenly on both response occasions. The study probably indicates that the recurrent rehabilitation periods at the centre have an effect. When the respondents respond to items with a global focus, they seem to indicate experiences of a higher QOL.


Multiple Metabolic Pathways of 2,4,6-Tribromophenol in Rice Plants.
Bromophenols occur naturally and are used globally as man-made additives in various industrial products. They are decomposition products of many emerging organic pollutants, such as tetrabromobisphenol A, polybrominated dibenzo- p-dioxin (PBDD), polybrominated diphenyl ethers (PBDE), and others. To characterize their biotransformation pathways, bromophenol congener 2,4,6-tribromophenol, being used most frequently in the synthesis of brominated flame retardants and having the greatest environmental abundance, was selected to hydroponically expose rice plants. After exposure for 5 days, 99.2% of 2,4,6-tribromophenol was metabolized by rice. Because of the lack of relative reference standards, an effective screening strategy was used to screen for potential metabolites that were further qualitatively identified by gas and liquid chromatography combined with high-resolution mass spectrometry. Forty transformation products were confirmed or tentatively identified at different confidence levels, including 9 phase I and 31 phase II metabolites. A large number of metabolites (39) were found in rice root, and 10 of them could be translocated and detected in rice stems or leaves. Many transformation pathways were proposed, including debromination, hydroxylation, methylation, coupling reactions, sulfation, and glycosylation. It was remarkable that a total of seven hydrophobic, persistent, and toxic OH-PBDEs and PBDD/Fs were found, indicating the biotic dimeric reactions of 2,4,6-tribromophenol that occurred in the rice plants. These results improve our understanding of the transformation and environmental fates of bromophenols, and they indicate new potential sources for OH-PBDEs and PBDD/Fs in the environment, especially in food chains.


Platelet extracellular vesicles induce a pro-inflammatory smooth muscle cell phenotype.
Extracellular vesicles (EVs) are mediators of cell communication during health and disease, and abundantly released by platelets upon activation or during ageing. Platelet EVs exert modulatory effects on immune and vascular cells. Platelet EVs may modulate the function of vascular smooth muscle cells (SMC). Platelet EVs were isolated from platelet-rich plasma and incubated with SMC in order to assess binding, proliferation, migration and pro-inflammatory phenotype of the cells. Platelet EVs firmly bound to resting SMC through the platelet integrin αIIbβ3, while binding also occurred in a CX3CL1-CX3CR1-dependent manner after cytokine stimulation. Platelet EVs increased SMC migration comparable to platelet derived growth factor or platelet factor 4 and induced SMC proliferation, which relied on CD40- and P-selectin interactions. Flow-resistant monocyte adhesion to platelet EV-treated SMC was increased compared with resting SMC. Again, this adhesion depended on integrin αIIbβ3 and P-selectin, and to a lesser extent on CD40 and CX3CR1. Treatment of SMC with platelet EVs induced interleukin 6 secretion. Finally, platelet EVs induced a synthetic SMC morphology and decreased calponin expression. Collectively, these data indicate that platelet EVs exert a strong immunomodulatory activity on SMC. In particular, platelet EVs induce a switch towards a pro-inflammatory phenotype, stimulating vascular remodelling.


Quality of general movements in preterm infants with transient periventricular echodensities.
By means of sequential videotape recordings, the relevance of the quality of general movements for neurological outcome was determined in a group of 21 appropriate-for-gestational-age preterm infants with transient periventricular echodensities of variable localization and duration and in 6 infants without echodensities. Echodensities, especially in the parieto-occipital area, affected the quality of general movements. Echodensities persisting beyond 14d were associated with abnormal general movements; infants with echodensities up to 14 d had either normal or abnormal general movements. The developmental course of movement quality was correlated to neurological outcome (p < 0.005): normal outcomes were found in 11/12 infants with normal general movements throughout and in 9/11 infants with transient abnormal general movements; all 4 infants with persistent abnormal general movements had impaired outcomes. In infants with transient echodensities, longitudinal assessment of the quality of general movements helps to determine if there is brain dysfunction, either transient or persistent, and identifies infants at risk for impaired neurological outcomes.


Reductive metabolism of the nitroimidazole-based hypoxia-selective cytotoxin NLCQ-1 (NSC 709257).
The enzymatic cell-free metabolism of the novel hypoxia-selective cytotoxin 4-[3-(2-nitro-1-imidazolyl)-propylamino]-7-chloroquinoline hydrochloride (NLCQ-1) was investigated under hypoxic or aerobic conditions in the presence of purified reductive enzymes or isolated rat liver microsomes by monitoring the parent compound with HPLC-UV analysis. Enzymatic reduction of NLCQ-1 with isolated rat liver microsomes and NADPH or NADH showed that, only under hypoxic conditions, ca. 45% and 60% of the parent compound was reduced, respectively, within 1 h of incubation (37 degrees C). Under identical conditions but in the presence of 2'-AMP (a P450 reductase inhibitor), 6-propyl-2-thiouracil or p-hydroxymercuribenzoate (cytochrome b5 reductase inhibitors), NLCQ-1 reduction was inhibited. Enzymatic cell-free metabolism of NLCQ-1 with recombinant human DT-diaphorase (DTD) and NADPH or NADH under hypoxic or aerobic conditions showed that < or = 5% of the compound was reduced within 2 h. Reduction kinetics with human P450 reductase-expressing microsomes showed ca. 75% or 50% reduction of NLCQ-1 under hypoxic or aerobic conditions, respectively, after 2 h incubation. These results suggest that DTD is not involved in the initial steps of the bioreductive metabolism of NLCQ-1, although it could be involved with metabolites of NLCQ-1, and that cytochrome P450 and cytochrome b5 reductases play a significant role in the bioreductive metabolism of NLCQ-1.


Musculoskeletal infection: findings on magnetic resonance imaging.
Magnetic resonance imaging (MRI) can provide considerable useful information in cases of musculoskeletal infection, in particular demonstrating the extent of involvement of soft tissues and medullary bone. Differentiation between infected tissue and abscess is also possible with MRI, especially if contrast agent is administered. MRI therefore serves as an adjunct to other imaging modalities, especially in complex cases. This review covers various manifestations of musculoskeletal infection as depicted with MRI.


[HIV infection status in male outpatients in sexually transmitted disease clinics in Tianjin, 2016-2020].
Objective: To understand the HIV infection status in male outpatients in sexually transmitted disease (STD) clinics in Tianjin from 2016 to 2020. Methods: According to the sentinel surveillance protocol, continuous cross-sectional studies were conducted between April and June during 2016-2020 to collect the information about the awareness of AIDS related knowledge, related sex behaviors, HIV infection, syphilis prevalence and HCV infection of male STD outpatients in Tianjin with a sample seize of 400 in each sentinel clinic. Results: From 2016 to 2020, a total of 4 000 male STD outpatients were surveyed. The HIV positive rate increased from 1.13% (9/800) to 2.25% (18/800) (trend χ2=14.22, P<0.001), the positive rate of syphilis increased from 9.38% (75/800) to 13.00% (104/800) (trend χ2=7.30, P=0.007) in this population during this period. The overall HCV positive rate was 0.45% (18/4 000). Multivariate logistic regression analysis showed that compared with those who were unmarried, had registered residence in Tianjin, had no temporary sexual behavior in the past 3 months, had no anal sex and had negative syphilis test result, the risk factors of HIV infection in the male STD outpatients included cohabitation (aOR=7.53, 95%CI:2.13-26.62), being from other provinces (aOR=3.64,95%CI:1.58-8.38), having temporary sexual behavior in the past 3 months (aOR=2.24,95%CI:1.03-4.89), having homosexual anal sex (aOR=85.99,95%CI:38.76-190.74) and suffering from syphilis (aOR=6.06,95%CI:3.18-11.56). Conclusion: The detection rates of HIV infection and syphilis in male STD outpatients in Tianjin showed upward trends from 2016 to 2020. Having temporary sexual behavior and anal sex, and suffering from syphilis were the main risk factors of HIV infection in male STD outpatients.


[Cytotoxicity of recombinant human tumor necrosis factor (rHTNF) alone and in combination with chemotherapeutic agents on human ovarian cancer cells].
The cytotoxic activities of recombinant human tumor necrosis factor (rHTNF) and five chemotherapeutic agents, CTX, 5-FU, VCR, DDP, KSM, against two human ovarian cancer cell lines, OVCAR3 and CAOV3, using the MTT assay were studied. The result showed that cytotoxicities of rHTNF at 5 x 10(4)-5 x 10(7) U/L against CAOV3 cell line for 24h exposure were from 14.2% +/- 6.8% to 67.2% +/- 3.0%, and that against CAOV3 cell line were from 8.2% +/- 4.3% to 60.9% +/- 1.3%. The cytotoxic effects of all five chemotherapeutic agents against the two cell lines were much lower than that of rHTNF. Various degrees of synergistic enhancement cytotoxicities of DDP or KSM in combination with rHTNF were assessed. Especially, distinct synergistic effects of a low dose, 50kU/L, or rHTNF with nearly all concentration (10(-4)-10(-1) mg/L) of KSM were obtained on the two cell lines.


Monoterpene glucosides in Eustoma grandiflorum roots promote hyphal branching in arbuscular mycorrhizal fungi.
Host plant-derived strigolactones trigger hyphal branching in arbuscular mycorrhizal (AM) fungi, initiating a symbiotic interaction between land plants and AM fungi. However, our previous studies revealed that gibberellin-treated lisianthus (Eustoma grandiflorum, Gentianaceae) activates rhizospheric hyphal branching in AM fungi using unidentified molecules other than strigolactones. In this study, we analyzed independent transcriptomic data of E. grandiflorum and found that the biosynthesis of gentiopicroside (GPS) and swertiamarin (SWM), characteristic monoterpene glucosides in Gentianaceae, was upregulated in gibberellin-treated E. grandiflorum roots. Moreover, these metabolites considerably promoted hyphal branching in the Glomeraceae AM fungi Rhizophagus irregularis and Rhizophagus clarus. GPS treatment also enhanced R. irregularis colonization of the monocotyledonous crop chive (Allium schoenoprasum). Interestingly, these metabolites did not provoke the germination of the root parasitic plant common broomrape (Orobanche minor). Altogether, our study unveiled the role of GPS and SWM in activating the symbiotic relationship between AM fungi and E. grandiflorum.


The aphid Pentalonia nigronervosa (Hemiptera: Aphididae) takes advantage from the quality change in banana plant associated with Banana bunchy top virus infection.
Viral diseases can change plant metabolism, with potential impacts on the quality of the plant's food supply for insect pests, including virus vectors. The banana aphid, Pentalonia nigronervosa Coquerel, is the vector of the Banana bunchy top virus (BBTV), the causal agent of Banana bunchy top disease (BBTD), the most devastating viral disease of bananas in the world. The effect of BBTV on the life-history traits and population dynamics of P. nigronervosa remains poorly understood. We therefore studied the survival rate, longevity, daily fecundity per aphid, tibia length, population growth, and winged morph production of a P. nigronervosa clone grown on healthy or infected, dessert, or plantain banana plants. We found that daily fecundity was higher on infected banana than on healthy banana plants (plantain and dessert), and on plantain than on dessert banana plants (healthy and infected). Survival and longevity were lower on infected dessert bananas than on other types of bananas. In addition, virus infection resulted in a decrease in aphid hind tibia length on both plant genotypes. The survival and fecundity table revealed that the aphid net reproduction rate (Ro) was highest on plantains (especially infected plantain), and the intrinsic growth rate (r) was highest on infected plants. Finally, the increase of aphids and alate production was faster first on infected plantain, then on healthy plantain, and lower on dessert banana (infected and uninfected). Our results reinforce the idea of indirect and plant genotype-dependent manipulation of P. nigronervosa by the BBTV.


[Gram-positive cocci as an opportunistic infection factor].
The frequency of opportunistic infections increased in the last years. The opportunistic infections are serious and very difficult to diagnose complication at patients with lower immunity. The following factors are conducive to develop infections caused by opportunistic bacteria: invasive research methods, medical treatments and immunological defects. The publication presents pathogenicity of bacteria of following types: Aerococcus, Kocuria, Kytococcus, Lactococcus, Leuconostoc, Micrococcus, Pediococcus. There are also mentioned diagnostic and treatment issues in the publication. The purpose of this study is to draw attention to infection caused by opportunistic bacteria, which are ingredients of physiological flora as well as diagnostic difficulties, which occur in case of isolation of this pathogens. Quick and correct diagnosis of etiological factor and applying of proper treatment can have very important impact on effectiveness of therapy and decrease of mortality in this kind of infections.


Mental workload and neural efficiency quantified in the prefrontal cortex using fNIRS.
An improved understanding of how the brain allocates mental resources as a function of task difficulty is critical for enhancing human performance. Functional near infrared spectroscopy (fNIRS) is a field-deployable optical brain monitoring technology that provides a direct measure of cerebral blood flow in response to cognitive activity. We found that fNIRS was sensitive to variations in task difficulty in both real-life (flight simulator) and laboratory settings (tests measuring executive functions), showing increased concentration of oxygenated hemoglobin (HbO2) and decreased concentration of deoxygenated hemoglobin (HHb) in the prefrontal cortex as the tasks became more complex. Intensity of prefrontal activation (HbO2 concentration) was not clearly correlated to task performance. Rather, activation intensity shed insight on the level of mental effort, i.e., how hard an individual was working to accomplish a task. When combined with performance, fNIRS provided an estimate of the participants' neural efficiency, and this efficiency was consistent across levels of difficulty of the same task. Overall, our data support the suitability of fNIRS to assess the mental effort related to human operations and represents a promising tool for the measurement of neural efficiency in other contexts such as training programs or the clinical setting.


[Transfer factor as adjuvant immunotherapy in invasive cervix cancer. Report of a double-blind study].
From 1977 to 1982 a prospective randomized double-blind study comparing transfer-factor (TF) versus placebo was conducted in invasive cervical cancer patients after radical surgery and irradiation. The husbands of the cancer patients were selected as leukocyte donors for TF preparations. 60 patients entered the study; 28 patients received placebo and 32 patients received TF. The comparability of both collectives was excellent concerning age and tumor stage. One patient treated with TF died intercurrently. The rate of recurrence of cancer was 5 in the 31 TF-treated patients and 11 in the 28 patients receiving placebo, which was significantly different (p less than 0,05). This difference was even greater when only patients treated for at least 3 months were compared (3 recurrences in the TF-group and 11 recurrences in the placebo-group). Further aspects of this clear clinical results are discussed.


Characterization of the 3-O-methylgallate dioxygenase gene and evidence of multiple 3-O-methylgallate catabolic pathways in Sphingomonas paucimobilis SYK-6.
Sphingomonas paucimobilis SYK-6 is able to grow on various lignin-derived biaryls as the sole source of carbon and energy. These compounds are degraded to vanillate and syringate by the unique and specific enzymes in this strain. Vanillate and syringate are converted to protocatechuate (PCA) and 3-O-methylgallate (3MGA), respectively, by the tetrahydrofolate-dependent O-demethylases. Previous studies have suggested that these compounds are further degraded via the PCA 4,5-cleavage pathway. However, our subsequent analysis of the ligB insertion mutant, which encodes the beta subunit of PCA 4,5-dioxygenase, suggested that at least one alternative route is involved in 3MGA degradation. In the present study, we isolated the desZ gene, which confers 3MGA degradation activity on Escherichia coli. The deduced amino acid sequence of desZ showed ca. 20 to 43% identity with the type II extradiol dioxygenases. Gas chromatography-mass spectrometry analysis suggested that DesZ catalyzes the 3,4-cleavage of 3MGA. Disruption of both desZ and ligB in SYK-6 resulted in loss of the dioxygen-dependent 3MGA transformation activity, but the resulting mutant retained the ability to grow on syringate. We found that the cell extract of the desZ ligB double mutant was able to convert 3MGA to gallate when tetrahydrofolate was added to the reaction mixture, and the cell extract of this mutant degraded gallate to the same degree as the wild type did. All these results suggest that syringate is degraded through multiple 3MGA degradation pathways in which ligAB, desZ, 3MGA O-demethylase, and gallate dioxygenase are participants.


Genetic analysis of adventitious root formation with a novel series of temperature-sensitive mutants of Arabidopsis thaliana.
When cultured on media containing the plant growth regulator auxin, hypocotyl explants of Arabidopsis thaliana generate adventitious roots. As a first step to investigate the genetic basis of adventitious organogenesis in plants, we isolated nine temperature-sensitive mutants defective in various stages in the formation of adventitious roots: five root initiation defective (rid1 to rid5) mutants failed to initiate the formation of root primordia; in one root primordium defective (rpd1) mutant, the development of root primordia was arrested; three root growth defective (rgd1, rgd2, and rgd3) mutants were defective in root growth after the establishment of the root apical meristem. The temperature sensitivity of callus formation and lateral root formation revealed further distinctions between the isolated mutants. The rid1 mutant was specifically defective in the reinitiation of cell proliferation from hypocotyl explants, while the rid2 mutant was also defective in the reinitiation of cell proliferation from root explants. These two mutants also exhibited abnormalities in the formation of the root apical meristem when lateral roots were induced at the restrictive temperature. The rgd1 and rgd2 mutants were deficient in root and callus growth, whereas the rgd3 mutation specifically affected root growth. The rid5 mutant required higher auxin concentrations for rooting at the restrictive temperature, implying a deficiency in auxin signaling. The rid5 phenotype was found to result from a mutation in the MOR1/GEM1 gene encoding a microtubule-associated protein. These findings about the rid5 mutant suggest a possible function of the microtubule system in auxin response.


Shear stress and aneurysms: a review.
Wall shear stress, the frictional force of blood flow tangential to an artery lumen, has been demonstrated in multiple studies to influence aneurysm formation and risk of rupture. In this article, the authors review the ways in which shear stress may influence aneurysm growth and rupture through changes in the vessel wall endothelial cells, smooth-muscle cells, and surrounding adventitia, and they discuss shear stress-induced pathways through which these changes occur.


Employing non-canonical amino acids towards the immobilization of a hyperthermophilic enzyme to increase protein stability.
A carboxylesterase derived from Sulfolobus solfataricus P1 was immobilized onto an epoxy-activated Sepharose resin via non-canonical amino acids. The immobilized enzyme exhibited heightened performance in organic solvents, recyclability, and stability at room temperature for over two years. The incorporation of a non-canonical amino acid afforded a high degree of control over the bioorthogonal immobilization reaction. These results indicate that the specificity conferred by genetic code expansion produces advantages in protein immobilization and broadens the utility of such proteins to non-biological settings.


Therapeutic upper gastrointestinal endoscopy. Past, present, and future.
Therapeutic procedures in upper gastrointestinal endoscopy are usually performed with the patient under sedation, and there is a clear advantage with video endoscopy. The endoscopy assistant needs full training on the appropriate and safe use of equipment and accessories. Complications of procedures should be detected early and managed appropriately. Indications, results, and perspectives of endoscopic procedures are reviewed for the following situations: gastrointestinal bleeding, caustic injury, foreign bodies, advanced and superficial cancer, dysplasia, reflux esophagitis, motility disorders, and nutritional assistance. Consolidation of current methods and systematic evaluation of the results of therapeutic endoscopy are important tasks for the near future.


Desmoplastic fibroma of the rib.
Desmoplastic fibroma is a very rare primary tumor of bone, closely related to aggressive fibromatosis of soft tissue. Although considered a benign lesion, it is locally destructive, can extend into the soft tissues, and has a high rate of local recurrences after incomplete surgical excision. Recognition of this entity is important to ensure proper surgical treatment. According to the published data, the tumor is most common in the long tubular bones (56%), the mandible (26%), and the pelvis (14%). Rib involvement by desmoplastic fibroma is extremely rare, and to our knowledge, only 3 cases have been reported in the literature to date. We present the case of a desmoplastic fibroma in the rib of a 19-year-old man, adding a fourth case to the previously reported cases involving this unusual location. The clinical history and the radiological and pathologic findings are presented.


The discriminator base influences tRNA structure at the end of the acceptor stem and possibly its interaction with proteins.
For many tRNAs, the discriminator base preceding the CCA sequence at the 3' end is important for aminoacylation. We show that the discriminator base influences the stability of the 1.72 base pair onto which it is stacked. Mutations of the discriminator base from adenosine to cytidine or uridine make the cytidine residue in the C1-G72 base pair of mutant Escherichia coli initiator tRNAs more reactive toward sodium bisulfite, the single-strand-specific reagent. The activity of the enzyme Met-tRNA transformylase toward these and other mutant initiator tRNAs is also consistent with destabilization of the 1.72 base pair in vitro and in vivo. By influencing the strength of the 1.72 base pair, the discriminator base could affect the energetic cost of opening the base pair and modulate the structure of the tRNA near the site of aminoacylation. For some aminoacyl-tRNA synthetases and other proteins that interact with tRNA, these factors could be important for specific recognition and/or formation of the transition state during catalysis.


Spinal retroflexion in craniorhachischisis: its classification and limitations.
Spinal retroflexion has been studied in five stillborn human fetuses having craniorhachischisis. The findings show that retroflexion in this variant of anencephaly can be classified into severe, moderate and mild forms. The three grades can be differentiated from one another by the direction of the face, shape of the mentothoracic junction, extension of hairline on back, radiographic abnormalities of the spine, and the diaphragmatic defects. It is discussed that, though the anencephalies with severe or moderate degree of cervical retroflexion resemble iniencephaly in their features of spinal retroflexion, those having mild retroflexion are contrasted and should not be categorised with iniencephaly. It is suggested that for precision the term "spinal retroflexion" should be used after duly prefixing it by an appropriate word (severe, moderate or mild) indicating the degree of retroflexion observed.


Robust and efficient design of experiments for the Monod model.
In this paper the problem of designing experiments for the Monod model, which is frequently used in microbiology, is studied. The model is defined implicitly by a differential equation and has numerous applications in microbial growth kinetics, environmental research, pharmacokinetics, and plant physiology. The designs presented so far in the literature are local optimal designs, which depend sensitively on a preliminary guess of the unknown parameters, and are for this reason in many cases not robust with respect to their misspecification. Uniform designs and maximin optimal designs are considered as a strategy to obtain robust and efficient designs for parameter estimation. In particular, standardized maximin D- and E-optimal designs are determined and compared with uniform designs, which are usually applied in these microbiological models. It is demonstrated that maximin optimal designs are substantially more efficient than uniform designs. Parameter variances can be decreased by a factor of two by simply sampling at optimal times during the experiment. Moreover, the maximin optimal designs usually provide the possibility for the experimenter to check the model assumptions, because they have more support points than parameters in the Monod model.


HER-2/neu and hTERT cryptic epitopes as novel targets for broad spectrum tumor immunotherapy.
Tolerance to tumor-nonmutated self proteins represents a major obstacle for successful cancer immunotherapy. Since this tolerance primarily concerns dominant epitopes, we hypothesized that targeting cryptic epitopes that have a low affinity for HLA could be an efficient strategy to breach the tolerance to tumor Ags. Using the P1Y heteroclitic peptide approach, we identified low affinity cryptic HLA-A*0201-restricted epitopes derived from two widely expressed tumor Ags, HER-2/neu and hTERT. The P1Y variants of four HER-2/neu (neu(391), neu(402), neu(466), neu(650))- and two hTERT (hTERT(572) and hTERT(988))-derived low affinity peptides exhibited strong affinity for HLA-A*0201 and stimulated specific CTL from healthy donor PBMCs. These CTL specifically recognized HER-2/neu- and hTERT-expressing tumor cells of various histological origins. In vivo studies showed that HLA-A*0201 transgenic HHD mice vaccinated with the P1Y variant peptides generated CTL that specifically lysed Ag-expressing tumor cells, thus recognizing the cognate endogenous Ags. These results suggest that heteroclitic variants of low affinity, cryptic epitopes of widely expressed tumor Ags may serve as valid tools for tumor immunotherapy.


A primary care perspective of posttraumatic stress disorder for the Department of Veterans Affairs.
Posttraumatic stress disorder (PTSD) is a major mental disorder associated with significant morbidity, psychosocial impairment, and disability. The diagnosis of PTSD can be missed in a primary care setting, as patients frequently present with somatic complaints or depression and are often reluctant to discuss their traumatic experiences. As recent studies of veterans returning from the Gulf War and the Iraqi War suggest high rates of PTSD, the U.S. Department of Veterans Affairs (VA) Hospitals are gearing up to face this challenge. It is important to screen these veterans for symptoms of PTSD and make an appropriate referral if required. In this article, we attempt to review PTSD with a special focus on the VA population. In addition to discussing the epidemiology, diagnosis, and treatment options for PTSD, we also suggest screening questions for both combat-related and military sexual trauma-related PTSD.


Enhancement by grapefruit juice of morphine antinociception.
The aim of this study was to investigate the effect of grapefruit juice intake on the antinociception of morphine in rats. The antinociception of morphine (30 mg/kg, per os (p.o.)) was significantly enhanced by the oral administration of grapefruit juice (2 ml/rat). Further, the effect of grapefruit juice was examined in morphine-tolerant rats. The repeated administration of morphine (100 mg/kg p.o.) for 5 d caused a marked decrease in the antinociception, indicating the development of morphine-tolerance. In the morphine-tolerant rats, oral administration of grapefruit juice potentiated significantly the antinociceptive effect of morphine. To examine the pharmacokinetics of morphine after the repeated treatment with morphine for 5 d, microdialysis probes were implanted into the jugular vein and spinal intrathecal space in rats. The morphine concentrations in the blood and intrathecal cerebrospinal fluid (CSF) were gradually decreased by the repeated treatment with morphine. The grapefruit juice treatment significantly increased the blood concentration of morphine in morphine-tolerant rats. These results suggest that oral administration of grapefruit juice enhances the morphine antinociception by increasing the intestinal absorption of this agent.


[Imaging diagnosis of ovarian tumors. Magnetic resonance tomography in comparison with computerized tomography and sonography].
The present paper compares the results of MRT with sonography in 64 patients with tumours of the adnexa in 35 patients examined by CT. There was no difference between these three imaging methods as regards lateralisation of the lesion. MRT provided better differentiation because of the excellent demonstration of the uterus and of tumours of the adnexa. Detailed tissue characterisation, particularly as regards cystic lesions, provides improved diagnostic information. MRT has problems, however, because of its low spatial resolution and the difficulty in differentiation from bowel loops. At present sonography and CT is better at establishing a differential diagnosis. CT remains the method of choice for tumour staging.


Description and validation of the apnea risk evaluation system: a novel method to diagnose sleep apnea-hypopnea in the home.
To evaluate the accuracy and practicality of the Apnea Risk Evaluation System (ARES; Advanced Brain Monitoring; Carlsbad, CA), a limited-channel system for diagnosing sleep apnea/hypopnea in the home. Prospective randomized study with blinded analysis. Two independent, community-based, sleep-disorders centers and the participants' homes. Two hundred ninety-nine subjects were recruited, including 210 consecutive willing patients referred by community physicians to the centers because of suspected sleep apnea; 36 "general medical" patients recruited from community physicians' offices; and 53 "presumably healthy" subjects recruited from community centers. Manual scoring of attended in-laboratory full-night or split-night polysomnography by trained technologists supervised by physicians board certified in sleep medicine, and automated scoring of the limited-channel system used attended in the laboratory and unattended at home. The definition of the polysomnography apnea-hypopnea index (AHI) and the ARES respiratory disturbance index was the total number of events divided by the study duration in hours. Two hundred eighty-four valid comparisons of in-laboratory simultaneous polysomnography and ARES and 187 valid comparisons of in-laboratory polysomnography with a separate 2 nights of unattended self-applied ARES Unicorder (Advanced Brain Monitoring) were obtained. A diagnostic AHI cutoff of > 10 was used to establish the accuracy and validity of the ARES. The concurrent in-laboratory comparison yielded a sensitivity of 97.4, a specificity of 85.6, a positive predictive value of 93.6, and a negative predictive value of 93.9; in-home comparison sensitivity, specificity, positive predictive value, and negative predictive value were 91.5, 85.7, 91.5, and 85.7, respectively. The ARES demonstrated consistently high sensitivity and specificity for both in-laboratory and in-home recordings. In patients at risk for sleep apnea who do not a priori need an attended study, the ARES could provide a low-cost alternative to traditional polysomnography.


Comparison of phenoxybenzamine and doxazosin in perioperative management of patients with pheochromocytoma.
Adrenalectomy with preoperative pharmacological preparation is strongly recommended in patients diagnosed with pheochromocytoma, in order to prevent perioperative complications. To compare phenoxybenzamine (PhB) and doxazosin (DOX) in terms of perioperative haemodynamic status in patients with pheochromocytoma, who have been prepared for adrenalectomy. Retrospective analysis of 44 patients with pheochromocytoma (aged 16-80 years, 29 females) who underwent adrenalectomy. Patients were divided into two groups: 35 patients on DOX and nine patients on PhB. Mean time of preparation for surgery was 38.8 days in the DOX group and 18.3 days in the PhB group (p = 0.04). No statistically significant differences between the DOX and PhB groups in intraoperative blood pressure (BP) fluctuations were found: < 170/100 mm Hg (34% vs. 44%, respectively, p = 0.42), ≥ 200/110 mm Hg (40% vs. 22%, respectively, p = 0.28). Mean greatest intraoperative systolic BP (195 ± 53 vs. 166 ± 42 mm Hg, p = 0.21) and diastolic BP (98 ± 20 vs. 89 ± 46 mm Hg, p = 0.21), and mean lowest intraoperative systolic BP (87 ± 13 vs. 79 ± 17 mm Hg, p = 0.25) and diastolic BP (49 ± 8 vs. 46 ± 12 mm Hg, p = 0.60) were not different between the DOX and PhB groups, respectively. Sodium nitroprusside was administrated in 30% DOX vs. 11% PhB patients (p = 0.25). Laparoscopic surgery was conducted in 97% DOX vs. 89% PhB patients (p = 0.64). Postoperative BP drop below 90/60 mm Hg was noted in 48% of the DOX vs. 43% of the PhB group (p = 0.56). Negative correlation was found between the length of DOX administration with maximal intraoperative systolic BP (r = -0.45, p = 0.006) and diastolic BP (r = -0.39, p = 0.019). There are no clinically relevant differences between patients with pheochromocytoma, who have been prepared for adrenalectomy with DOX or PhB.


Bacteremia and malaria in Tanzanian children hospitalized for acute febrile illness.
We recorded the reason for presentation to a rural hospital in an area endemic for malaria in 909 children between January 2006 and March 2009. Blood smears were examined for Plasmodium falciparum parasites, and blood spots dried on filter paper were prepared for 464 children. A PCR assay utilizing the stored blood spots was developed for Streptococcus pneumoniae (lytA) and Haemophilus influenzae (pal). Malaria was present in 299 children whose blood was tested by polymerase chain reaction (PCR); 19 had lytA and 15 had pal. The overall prevalence of lytA was 25 of the 464 children, while that of pal was 18 children. Fever was present in 369 children of whom 19 had lytA DNA while 11 had pal DNA detected. Of the 95 afebrile children, six had lytA and seven pal. We conclude that there are no clinical features that distinguish malaria alone from bacteremia alone or the presence of both infections.


Caffeine and adenosine A(2a) receptor antagonists prevent beta-amyloid (25-35)-induced cognitive deficits in mice.
Consumption of caffeine, an adenosine receptor antagonist, was found to be inversely associated with the incidence of Alzheimer's disease. Moreover, caffeine protects cultured neurons against beta-amyloid-induced toxicity, an effect mimicked by adenosine A(2A) but not A(1) receptor antagonists. We now tested if caffeine administration would prevent beta-amyloid-induced cognitive impairment in mice and if this was mimicked by A(2A) receptor blockade. One week after icv administration of the 25-35 fragment of beta-amyloid (Abeta, 3 nmol), mice displayed impaired performance in both inhibitory avoidance and spontaneous alternation tests. Prolonged treatment with caffeine (1 mg/ml) had no effect alone but prevented the Abeta-induced cognitive impairment in both tasks when associated with acute caffeine (30 mg/kg) 30 min treatment before Abeta administration. The same protective effect was observed after subchronic (4 days) treatment with daily injections of either caffeine (30 mg/kg) or the selective adenosine A(2A) receptor antagonist SCH58261 (0.5 mg/kg). This provides the first direct in vivo evidence that caffeine and A(2A) receptor antagonists afford a protection against Abeta-induced amnesia, which prompts their interest for managing Alzheimer's disease.


Azimilide for the treatment of atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia: results of a randomized trial and insights on the concordance of symptoms and recurrent arrhythmias.
Azimilide hydrochloride is an investigational antiarrhythmic medication that had shown evidence of efficacy in prolonging the time to recurrence of atrial fibrillation (AF) or atrial flutter (AFL) and paroxysmal supraventricular tachycardia (PSVT). This study was designed to confirm efficacy of 125 mg daily azimilide. The primary endpoint was ECG-documented recurrence of AF, AFL, or PSVT, followed for a maximum of 180 days. Four hundred eighty-two patients were enrolled in the United States and Canada (422 with AF or AFL and 60 with PSVT). The primary efficacy analysis included 402 patients with AF-AFL and 56 patients with PSVT. There was no significant difference in the time to first recurrence of symptomatic supraventricular arrhythmia in the AF-AFL stratum (median of 38 days for azimilide versus 27 days for placebo; hazard ratio [HR] of 1.14, P = 0.29). Similarly, there was no difference in time to recurrence in the PSVT stratum (>180 days for azimilide versus 135 days for placebo; HR = 1.28, P = 0.55). There were three deaths in the azimilide group and one in the placebo group. Four patients had nonsustained ventricular tachycardia (one torsades de pointes), all in the azimilide group. Asymptomatic recurrence was frequent in the AF-AFL group (8% with azimilide and 11% with placebo), but was absent in the PSVT group. False recurrence was common in both groups. Azimilide 125 mg daily was not associated with significant prolongation of the time to recurrent symptomatic supraventricular arrhythmias. There was substantial discordance between symptoms and recurrence.


Lignin peroxidase: resonance Raman spectral evidence for compound II and for a temperature-dependent coordination-state equilibrium in the ferric enzyme.
Resonance Raman (RR) spectroscopy of lignin peroxidase (ligninase, dairylpropane oxygenase) from the basidiomycete Phanerochaete chrysosporium suggests two different coordination states for the native ferric enzyme. Evidence for a high-spin, hexacoordinate ferric protoporphyrin IX was presented by Andersson et al. [Andersson, L. A., Renganathan, V., Chiu, A.A., Loehr, T. M., & Gold, M. H. (1985) J. Biol. Chem. 260, 6080-6087], whereas Kuila et al. [Kuila, D., Tien, M., Fee, J. A., & Ondrias, M. R. (1985) Biochemistry 24, 3394-3397] proposed a high-spin, pentacoordinate ferric system. Because the two RR spectral studies were performed at different temperatures, we explored the possibility that lignin peroxidase might exhibit temperature-dependent coordination-state equilibria. Resonance Raman results presented herein indicate that this hypothesis is indeed correct. At or near 25 degrees C, the ferric iron of lignin peroxidase is predominantly high spin, pentacoordinate; however, at less than or equal to 2 degrees C, the high-spin, hexacoordinate state dominates, as indicated by the frequencies of well-documented spin- and coordination-state marker bands for iron protoporphyrin IX. The temperature-dependent behavior of lignin peroxidase is thus similar to that of cytochrome c peroxidase (CCP). Furthermore, lignin peroxidase, like horseradish peroxidase (HRP) and CCP, clearly has a vacant coordination site trans to the native fifth ligand at ambient temperature. High-frequency RR spectra of compound II of lignin peroxidase are also presented. The observed shifts to higher frequency for both the oxidation-state marker band v4 and the spin- and coordination-state marker band v10 are similar to those reported for the compound II forms of HRP and lactoperoxidase and for ferryl myoglobin.(ABSTRACT TRUNCATED AT 250 WORDS)


Na+-H+ exchanger and proton channel in heart failure associated with Becker and Duchenne muscular dystrophies.
Cardiomyopathy is found in patients with Duchenne (DMD) and Becker (BMD) muscular dystrophies, which are linked muscle diseases caused by mutations in the dystrophin gene. Dystrophin defects are not limited to DMD but are also present in mild BMD. The hereditary cardiomyopathic hamster of the UM-X7.1 strain is a particular experimental model of heart failure (HF) leading to early death in muscular dystrophy (dystrophin deficiency and sarcoglycan mutation) and heart disease (δ-sarcoglycan deficiency and dystrophin mutation) in human DMD. Using this model, our previous work showed a defect in intracellular sodium homeostasis before the appearance of any apparent biochemical and histological defects. This was attributed to the continual presence of the fetal slow sodium channel, which was also found to be active in human DMD. Due to muscular intracellular acidosis, the intracellular sodium overload in DMD and BMD was also due to sodium influx through the sodium-hydrogen exchanger NHE-1. Lifetime treatment with an NHE-1 inhibitor prevented intracellular Na+ overload and early death due to HF. Our previous work also showed that another proton transporter, the voltage-gated proton channel (Hv1), exists in many cell types including heart cells and skeletal muscle fibers. The Hv1 could be indirectly implicated in the beneficial effect of blocking NHE-1.


Macromolecular Systems with MSA-Capped CdTe and CdTe/ZnS Core/Shell Quantum Dots as Superselective and Ultrasensitive Optical Sensors for Picric Acid Explosive.
This work reports the development of highly fluorescent materials for the selective and efficient detection of picric acid explosive in the nanomolar range by fluorescence quenching phenomenon. Poly(vinyl alcohol) grafted polyaniline (PPA) and its nanocomposites with 2-mercaptosuccinic acid (MSA)-capped CdTe quantum dots (PPA-Q) and with MSA-capped CdTe/ZnS core/shell quantum dots (PPA-CSQ) are synthesized in a single step free radical polymerization reaction. The thermal stability and photo stability of the polymer increases in the order of PPA < PPA-Q < PPA-CSQ. The polymers show remarkably high selectivity and efficient sensitivity toward picric acid, and the quenching efficiency for PPA-CSQ reaches up to 99%. The detection limits of PPA, PPA-Q, and PPA-CSQ for picric acid are found to be 23, 1.6, and 0.65 nM, respectively, which are remarkably low. The mechanism operating in the quenching phenomenon is proposed to be a combination of a strong inner filter effect and ground state electrostatic interaction between the polymers and picric acid. A portable and cost-effective electronic device for the visual detection of picric acid by the sensory system is successfully fabricated. The device is further employed for quantitative detection of picric acid in real water samples.


Cardiovascular surgery in Loeys-Dietz syndrome types 1-4.
The first publication of Loeys-Dietz syndrome (LDS) described aortic rupture at young ages. Experience with new LDS types showed that the clinical course varies, and thresholds for prophylactic surgery are discussed. As this is an uncommon disease, experience needs to be shared. Retrospective review of patients with LDS types 1-4 undergoing cardiovascular surgery during the years 1991-2016. Thirty-five patients (including 6 children with LDS2) underwent 57 operations. LDS 1, 2, 3 and 4 included 4, 17, 11 and 3 patients, respectively. Mean age at first surgery was 36 years, with a non-significant trend that LDS2 patients were younger. Of the 9 emergency surgeries, 7 were type A dissections, with 1 postoperative death. Twenty-two patients had prophylactic aortic root surgery (17 valve-sparing root replacements), with 1 postoperative death, 1 reoperation with valve replacement and 1 late death. Freedom from root reintervention and death was 92% at 13 years. Of the 11 patients with LDS3, 5 needed mitral valve surgery. Mitral valve disease was not found in the other LDS types. Ten patients needed >1 operation. Of the 57 operations, 33 were in the ascending aorta, 20 in the aorta distal to the arch including branches and 4 were isolated heart surgeries. Of the 20 vascular operations, 16 were in LDS2. Cumulative survival 20 years after first surgery (all patients) was 94.3%. Clinical course seems to be more aggressive in LDS2, with index operation at a younger age, and higher risk of needing several operations. Vascular disease distal to the arch is not uncommon. LDS3 seems to be associated with mitral valve disease. Prophylactic aortic root surgery is safe and durable.


The shift of macrophages toward M1 phenotype promotes aortic valvular calcification.
The purpose of the present study was to comprehensively compare the phenotype profile of infiltrated macrophages in human noncalcified and calcific aortic valves, and to determine whether the shift of macrophage polarization modulates valvular calcification in vitro. Cell surface markers of macrophages and inflammatory cytokines expression in 90 cases of human noncalcified and calcific aortic valve leaflets were analyzed. The normal aortic valve interstitial cells were isolated and cultured in vitro. After incubation with nonconditioned medium and conditioned medium from unstimulated or lipopolysaccharide-stimulated U937 monocytes, valve interstitial cells were evaluated by osteogenic differentiation markers. Infiltration of macrophages was enhanced in the calcific aortic valves, and M1 phenotype was the predominant macrophage subsets. In addition, both proinflammatory and anti-inflammatory cytokines were significantly upregulated in the calcific aortic valves. Furthermore, lipopolysaccharide-stimulated monocytes presented with increased expression of inducible nitric oxide synthase and high proportional CD11c-positive (M1) macrophages. Conditioned medium from unstimulated monocytes promoted the osteogenic differentiation of valve interstitial cells in vitro, as evidenced by increased markers such as bone morphogenetic protein 2, osteopontin, and alkaline phosphatase. Conditioned medium from M1 macrophages further enhanced valve interstitial cells calcification. Enzyme-linked immunosorbent assay showed that M1 phenotype macrophages secreted tumor necrosis factors α and interleukin 6, and neutralizing antibodies to these 2 proinflammatory cytokines attenuated induction of osteogenic differentiation and calcification by the conditioned media. Both total numbers and polarization of macrophage influence the process of calcification in human aortic valve. The shift toward M1 phenotype might promote valve interstitial cell calcification.


Something for the weekend! Saturday services - what do patients want and what do they need?
We investigated our patients' preferences for weekend services at the same time as commencing a new Saturday clinic. Patients were asked for their views on weekend services: 374 questionnaires were returned; 210 (56%) from women and 164 (44%) from men. Saturday services were rated as more important than Sunday services. One hundred and eleven patients (29.7%) said they would be likely/very likely to use a Saturday service, whereas only 67 (17.9%) rated Sunday services as important/very important. We also undertook an evaluation of our new Saturday service. A total of 214 patients (187 new/rebooks and 27 follow-ups) attended during the first 12 weeks; average 18 patients per clinic; 107 (50%) men. Introducing text appointment reminders reduced did not attend (DNA) rates from 19% to 14% (background clinic DNA rate 10%). There were more men (P = 0.01), more patients with symptoms (P < 0.0001) and more with sexually transmitted infections (STIs) (P = 0.02) attending on Saturdays. We have increased access for those patients who have difficulty attending on weekdays (56%), reduced anxiety (44%) and accessed a population with a high prevalence of STIs (44%). We conclude our Saturday service is affordable, sustainable and in patients' interests. Other clinics may wish to look at the needs of their local population and design services appropriate to their own area.


Body inversion effect in monkeys.
Humans visually process human body images depending on the configuration of the parts. However, little is known about whether this function is evolutionarily shared with nonhuman animals. In this study, we examined the body posture discrimination performance of capuchin monkeys, a highly social platyrrhine primate, in comparison to humans. We demonstrate that, like humans, monkeys exhibit a body inversion effect: body posture discrimination is impaired by inversion, which disrupts the configural relationships of body parts. The inversion effect in monkeys was observed when human body images were used, but not when the body parts were replaced with cubic and cylindrical figures, the positions of the parts were scrambled, or only part of a body was presented. Results in human participants showed similar patterns, though they also showed the inversion effect when the cubic/cylindrical body images were used. These results provide the first evidence for configural processing of body forms in monkeys and suggest that the visual attunement to social signals mediated by body postures is conserved through the evolution of primate vision.


Defects in signal transduction caused by a T cell receptor beta chain substitution.
An antigen-specific T-T hybridoma was mutagenized with ethylmethane sulfonate and negatively selected by anti-Ly-6 antibody-induced growth inhibition. One of the mutants generated, M4/8, had lost surface expression of a T cell receptor (TcR) V beta 8 epitope detected on the surface of the parental cell line. However, the mutant cell line did express high levels of TcR heterodimer as detected with a pan-specific anti-TcR antibody. CD3 epsilon, Ly-6 and Thy-1 were expressed at levels similar to the wild-type parental cell line. Analysis of the surface TcR/CD3 complexes by immunoprecipitation and two-dimension gel electrophoresis confirmed that the major discernable difference between the wild-type and mutant TcR/CD3 complexes resided in the TcR beta chain. The parental cell line had the potential to express two TcR heterodimers, V alpha V beta 1 and V alpha V beta 8, as determined by Northern blot analysis. Co-modulation experiments suggested that both types of receptors were expressed. However, the V alpha V beta 8 receptor was the predominant form. In contrast, the mutant M4/8 cell line did not synthesize V beta 8 mRNA and, thus, only the V alpha V beta 1 TcR was synthesized. Despite the normal surface expression of TcR/CD3 complex, the M4/8 mutant cell line did not produce interleukin 2 (IL 2) in response to antigen or soluble anti-CD3 epsilon monoclonal antibody (mAb). Furthermore, it responded poorly to concanavalin A, phytohemagglutinin and anti-Ly-6 mAb. Cross-linking of the stimulatory antibodies partially restored the IL 2 response to anti-CD3 epsilon or anti-Ly-6 to wild-type levels. Phorbol ester and ionomycin stimulated a full IL 2 response in the M4/8 cell line, demonstrating that the defect in the decreased signaling in the mutant did not result from a defect in the IL 2 gene program. In conclusion, these data suggested that the pairing of alpha/beta heterodimer not only determined antigen/MHC specificity but also the signaling efficiency of the TcR/CD3 complex.


Left vagus nerve stimulation in children with refractory epilepsy: an update.
This report updates previous reports regarding the tolerance and efficacy of periodic vagus nerve stimulation in a group of 19 children with medically and surgically intractable epilepsy. After vagal stimulator implantation, follow-up continued from 2 months to 30 months, with the study period ending in October 1995. Of the 19 patients, 6 (32%) had more than a 90% reduction in the number of monthly seizures, and 10 (53%) had more than a 50% reduction. Global evaluation scores indicated that only 1 patient had deterioration from baseline, 5 had no change, and the remainder had modest to remarkable improvement. All 3 children with unsuccessful corpuscallosotomy had improvement after implantation of the stimulator, and 5 of 6 children with Lennox-Gastaut syndrome had a 90% reduction of seizures. Five patients required fewer antiepileptic medications, and 1 patient had an increase in medication. Adversities included 2 possible wound infections, 1 instance of generator failure, and hoarseness during stimulation in all patients. Changing stimulation parameters to increase the rate of stimulation and reduce the interval between stimulations resulted in improved seizure control in 4 of 5 patients. Periodic VNS was well tolerated by these children and may have a role in the management of refractory epilepsy.


Risk of anaphylaxis after vaccination of children and adolescents.
To quantify the risk of anaphylaxis after vaccination of children and adolescents. The study population consisted of children and adolescents who were enrolled at 4 health maintenance organizations that participated in the Vaccine Safety Datalink Project. For the period 1991-1997, we identified potential cases by searching for occurrences of International Classification of Diseases, Ninth Revision (ICD-9) code 995.0 (anaphylactic shock), E948.0 through E948.9 (adverse reaction from bacterial vaccines), and E949.0 through E949.9 (adverse reaction from other vaccines and biological substances). At 1 study site, we also included a range of other allergy codes. We restricted to diagnoses on days 0 to 2 after vaccination (ICD-9 995.0) or day 0 (all other ICD-9 codes). We then reviewed the medical record to confirm the diagnosis. We identified 5 cases of potentially vaccine-associated anaphylaxis after administration of 7 644 049 vaccine doses, for a risk of 0.65 cases/million doses (95% confidence interval: 0.21-1.53). None of the episodes resulted in death. Vaccines that were administered before the anaphylactic episodes were generally given in combination and included measles-mumps-rubella, hepatitis B, diphtheria-tetanus, diphtheria-tetanus-pertussis, Haemophilus influenzae type b, and oral polio vaccine. One case of anaphylaxis followed measles-mumps-rubella vaccine alone. At the site at which we reviewed additional allergy codes, we identified 1 case after 653 990 vaccine doses, for a risk of 1.53 cases/million doses (95% confidence interval: 0.04-8.52). Patients and health care providers can be reassured that vaccine-associated anaphylaxis is a rare event. Nevertheless, providers should be prepared to provide immediate medical treatment should it occur.


Inhibitory effects of PGE1 on glucose induced insulin release in isolated islets of Langerhans.
Since prostaglandins are increasingly shown to play an important role on insulin secretion, an evaluation of the PGE1 action on insulin release by isolated islets of Langerhans has been undertaken. Pancreatic islets were prepared after a modification of the Lacy and Kostianovsky technique and incubated in Hanks solution containing glucose 1.63 or 16.3 mM and/or PGE1 10(-5) M. The insulin released was measured after 15, 30 or 60 min of incubation. The results obtained show that PGE1 does not modify insulin release induced by glucose 1.63 mM (non stimulant concentration) but that this PG significantly diminishes the insulin release induced by glucose 16.3 mM (stimulant concentration) after 15 and 30 min of incubation.


Colostomy irrigation: are we offering it enough?
This article discusses the use of irrigation for suitable colostomists and reasons why it can have a very positive effect on lifestyle. While it is evidence-based it also includes anecdotal tips from patients who irrigate. The suitability of patients to irrigate and ways to 'get started' with irrigation are discussed.


[General anesthesia for endobronchial laser therapy in a heart and lung transplant recipient].
The introduction of heart, lung and heart-and-lung transplants, only recently performed in Italy, has presented the anesthetist with the problem of the anesthesiological treatment of newly transplanted patients whose number will increase over time. For some time our unit has used general anesthesia using spontaneous breathing for endotracheal and endobronchial laser therapy. This solution was adopted in the case of a patient who had undergone a heart-lung transplant using an "a domino" technique some 90 days earlier. The authors discuss the results of the anesthesiological technique used taking into account the particular hemodynamic and respiratory characteristics of these patients.


Characterization of zona pellucida glycoprotein 3 (ZP3) and ZP2 binding sites on acrosome-intact mouse sperm.
There is considerable evidence that mouse fertilization requires the binding of sperm to two of the three glycoproteins that form the zona pellucida (ZP), ZP3 and ZP2. Despite the biologic importance of this binding, no one has demonstrated that sperm express separate, saturable, and specific binding sites for ZP3 and for ZP2. Such a demonstration is a prerequisite for defining the distribution, numbers, affinities, and regulation of function of ZP3 and ZP2 binding sites on sperm. The experiments reported herein used fluorochrome-labeled ZP3 and ZP2 and quantitative image analysis to characterize the saturable binding of ZP3 and ZP2 to distinct sites on living, capacitated, acrosome-intact mouse sperm. Approximately 20% of the ZP3 binding sites were found over the acrosomal cap, and the remaining sites were located over the postacrosomal region of the head. In contrast, ZP2 binding sites were detected only over the postacrosomal region. Saturation analysis estimated numbers and affinities of the binding sites for ZP3 (B(max) approximately 185 000 sites per sperm; K(d) approximately 67 nM) and ZP2 (B(max) approximately 500 000 sites per sperm; K(d) approximately 200 nM). Use of unlabeled ZP3, ZP2, and ZP1 as competitive inhibitors of the binding of fluorochrome-labeled ZP3 and ZP2 demonstrated that ZP3 and ZP2 bound specifically to their respective sites on sperm. Finally, we demonstrate that extracellular calcium as well as capacitation and maturation of sperm are required for these sites to bind their respective ligands.


Inkjet printing of paracetamol and indomethacin using electromagnetic technology: Rheological compatibility and polymorphic selectivity.
Drop-on-demand inkjet printing is a potential enabling technology both for continuous manufacturing of pharmaceuticals and for personalized medicine, but its use is often restricted to low-viscosity solutions and nano-suspensions. In the present study, a robust electromagnetic (valvejet) inkjet technology has been successfully applied to deposit prototype dosage forms from solutions with a wide range of viscosities, and from suspensions with particle sizes exceeding 2 μm. A detailed solid-state study of paracetamol, printed from a solution ink on hydroxypropyl methylcellulose (HPMC), revealed that the morphology of the substrate and its chemical interactions can have a considerable influence on polymorphic selectivity. Paracetamol ink crystallized exclusively into form II when printed on a smooth polyethylene terephthalate substrate, and exclusively into form I when in sufficient proximity to the rough surface of the HPMC substrate to be influenced by confinement in pores and chemical interactions. The relative standard deviation in the strength of the dosage forms was <4% in all cases, for doses as low as 0.8 mg, demonstrating the accuracy and reproducibility associated with electromagnetic inkjet technology. Good adhesion of indomethacin on HPMC was achieved using a suspension ink with hydroxypropyl cellulose, but not on an alternative polyethylene terephthalate substrate, emphasising the need to tailor the binder to the substrate. Future work will focus on lower-dose drugs, for which dosing flexibility and fixed dose combinations are of particular interest.


The effect of nitrous oxide on cerebral electrical activity.
Recordings of cerebral electrical activity produced by the cerebral function analysing monitor ( CFAM ) were obtained from nine healthy volunteers breathing increasing concentrations of N2O in O2. Concentrations of 30 and 50% N2O produced significant reductions in CFAM trace amplitude. Withdrawal of N2O resulted in an increase in amplitude with an initial increase above the control level. There were no consistent changes in the frequency distribution of the weighted electroencephalographic signal with increasing concentrations of N2O.


Quality assessment of occupational health and safety management at the level of business units making up the organizational structure of a coal mine: a case study.
The audit of the health and safety management system is understood as a form and tool of controlling. The objective of the audit is to define whether the undertaken measures and the obtained results are in conformity with the predicted assumptions or plans, whether the agreed decisions have been implemented and whether they are suitable in view of the accepted health and safety policy. This paper presents the results of an audit examination carried out on the system of health and safety management between 2002 and 2012 on a group of respondents, the employees of two mining departments (G-1 and G-2) of Jan, a coal mine. The audit was carried out using the questionnaire developed by the author based on the MERIT-APBK survey.


The Association of Reproductive Hormones During the Menstrual Period with Primary Dysmenorrhea.
This study aimed to investigate the association of reproductive hormones with primary dysmenorrhea in Chinese women. A case-control study was conducted and patients with primary dysmenorrhea and non-dysmenorrhea participants were recruited. Oxytocin, PGF2α, vasopressin, estriol and estradiol were respectively measured in plasma collected three to five days after menstruation. Restricted cubic spline and multiple logistic regression models were adopted to analyze the association between hormones and primary dysmenorrhea. There were 604 participants enrolled in our study including 300 patients with primary dysmenorrhea. After adjustment for the potential confounders, oxytocin levels (Q3: OR (95% CI) = 0.50 (0.27~0.95) (p=0.035); Q4: 0.34 (0.17~0.66) (p=0.001)) and PGF2α levels (Q3: 0.45 (0.24~0.87) (p=0.017); Q4: 0.43 (0.22~0.84) (p=0.013)) were respectively associated with an decreased risk of primary dysmenorrhea, but estradiol (Q2: 2.18 (1.13~4.19) (p=0.020); Q3: 2.17 (1.12~4.19) (p=0.022)) and vasopressin (Q3: 2.88 (1.48~5.63) (p=0.002); Q4: 3.20 (1.65~6.22) (p<0.001)) with an increased risk of primary dysmenorrhea, respectively. Among patients with primary dysmenorrhea, the higher estriol level was associated with higher frequent dysmenorrhea (Q2: 3.12 (1.32~7.34) (p=0.009); Q3: 4.97 (2.08~11.85) (p<0.001)) and always dysmenorrhea (Q2: 2.51 (1.03~6.11) (p=0.041); Q3: 3.10 (1.25~7.73) (p=0.015)). Similarly, high estriol levels were associated with the higher degree of pain significantly only when hormone levels were at a high level (Q3: 2.06 (1.03~4.18) (p=0.043)). Higher serum vasopressin and estradiol concentrations as well as lower oxytocin and PGF2α levels were associated with higher risk of primary dysmenorrhea. Estrogen showed a reverse U-shape association on the frequency and degree of pain among patients with primary dysmenorrhea.


MISSION!: optimization of acute and chronic care for patients with acute myocardial infarction.
Guideline implementation programs for patients with acute myocardial infarction (AMI) enhance adherence to evidence-based medicine (EBM) and improve clinical outcome. Although undertreatment of patients with AMI is well recognized in both acute and chronic phases of care, most implementation programs focus on acute and secondary prevention strategies during the index hospitalization phase only. Implementation of an all-phase integrated AMI care program maximizes EBM in daily practice and improves the care for patients with AMI. The objective of this study is to assess the effects of the MISSION! program on adherence to EBM for patients with AMI by the use of performance indicators. The MISSION! protocol is based on the most recent American College of Cardiology/American Heart Association and European Society of Cardiology guidelines for patients with AMI. It contains a prehospital, inhospital, and outpatient clinical framework for decision making and treatment, up to 1 year after the index event. MISSION! concentrates on rapid AMI diagnosis and early reperfusion, followed by active lifestyle improvement and structured medical therapy. Because MISSION! covers both acute and chronic AMI phase, this design implies an intensive multidisciplinary collaboration among all regional health care providers. Continuum of care for patients with AMI is warranted to take full advantage of EBM in day-to-day practice. This manuscript describes the rationale, design, and preliminary results of MISSION!, an all-phase integrated AMI care program.


Stepwise, Multi-Incisional, and Single-Stage Approach to Reshape Facial Contour After Large Cutaneous Lesion Resection.
Removal of large facial benign cutaneous lesions remains challenging. Serial or complete excisions together with local flaps or expander-based reconstructions are required. However, those techniques are time-consuming and may contribute to poor cosmetic and functional outcomes. The authors describe the resection and reconstruction of large facial benign cutaneous lesions by using Stepwise, Multi-Incisional, and Single-Stage (SMISS) approach. The authors performed a retrospective review from all patients with large facial benign cutaneous lesions who underwent "SMISS" approach for reconstruction between September 2013 and December 2014. The authors treated 47 patients (32 female and 15 male; mean age 23.5 years, range 9-50 years). Follow-up was for 12 months or longer. The mean length of major axis was 43.91 mm, minor axis 32.10 mm, and scar 66.91 mm. Good to excellent outcomes were achieved in all patients with a mean Vancouver scar scale score of 3.46 ± 0.39 (Cronbach α = 0.890) and mean visual analog scale score of 8.02 ± 0.69 (Cronbach α = 0.946). This was a nonrandomized, unblinded clinical case series with a limited sample size. For the excision and reconstruction of large facial benign cutaneous lesions, "SMISS" technique can be considered as a suitable option, leading to excellent results and a high patient satisfaction.


Stabilization and Structure of the cis Tautomer of a Free-Base Porphyrin.
Single-crystal X-ray analysis of the β-heptakis(trifluoromethyl)-meso-tetrakis(p-fluorophenyl)porphyrin, H2 [(CF3 )7 TpFPP], has revealed the first example of a stable cis tautomer of a free-base porphyrin, the long-postulated intermediate of porphyrin tautomerism. The stability of the unique molecule appears to reflect a dual origin: a strongly saddled porphyrin skeleton, which alleviates electrostatic repulsion between the two NH protons, and two polarization-enhanced, transannular N-H⋅⋅⋅O-H⋅⋅⋅N hydrogen bond chains, each involving a molecule of water. DFT calculations suggest that the observed tautomer has a lower energy than the alternative, doubly hydrated trans tautomer by some 8.3 kcal mol-1 . A fascinating prospect thus exists that H2 [(CF3 )7 TpFPP]⋅2 H2 O and cognate structures may act as supramolecular synthons, which, given their chirality, may even be amenable to resolution into optically pure enantiomers.


Predictive value of stroke discharge diagnoses in the Danish National Patient Register.
To determine the positive predictive values for stroke discharge diagnoses, including subarachnoidal haemorrhage, intracerebral haemorrhage and cerebral infarction in the Danish National Patient Register. Participants in the Danish cohort study Diet, Cancer and Health with a stroke discharge diagnosis in the National Patient Register between 1993 and 2009 were identified and their medical records were retrieved for validation of the diagnoses. A total of 3326 records of possible cases of stroke were reviewed. The overall positive predictive value for stroke was 69.3% (95% confidence interval (CI) 67.8-70.9%). The predictive values differed according to hospital characteristics, with the highest predictive value of 87.8% (95% CI 85.5-90.1%) found in departments of neurology and the lowest predictive value of 43.0% (95% CI 37.6-48.5%) found in outpatient clinics. The overall stroke diagnosis in the Danish National Patient Register had a limited predictive value. We therefore recommend the critical use of non-validated register data for research on stroke. The possibility of optimising the predictive values based on more advanced algorithms should be considered.


New Insights into the Disease Progression Control Mechanisms by Comparing Long-Term-Nonprogressors versus Normal-Progressors among HIV-1-Positive Patients Using an Ion Current-Based MS1 Proteomic Profiling.
For decades, epidemiological studies have found significant differences in the susceptibility to disease progression among HIV-carrying patients. One unique group of HIV-1-positive patients, the long-term-nonprogressors (LTNP), exhibits far superior ability in virus control compared with normal-progressors (NP), which proceed to Acquired Immune Deficiency Syndrome (AIDS) much more rapidly. Nonetheless, elucidation of the underlying mechanisms of virus control in LTNP is highly valuable in disease management and treatment but remains poorly understood. Peripheral blood mononuclear cells (PBMC) have been known to play important roles in innate immune responses and thereby would be of great interest for the investigation of the mechanisms of virus defense in LTNP. Here, we described the first comparative proteome analysis of PBMC from LTNP (n = 10) and NP (n = 10) patients using a reproducible ion-current-based MS1 approach, which includes efficient and reproducible sample preparation and chromatographic separation followed by an optimized pipeline for protein identification and quantification. This strategy enables analysis of many biological samples in one set with high quantitative precision and extremely low missing data. In total, 925 unique proteins were quantified under stringent criteria without missing value in any of the 20 subjects, and 87 proteins showed altered expressions between the two patient groups. These proteins are implicated in key processes such as cytoskeleton organization, defense response, apoptosis regulation, intracellular transport, etc., which provided novel insights into the control of disease progressions in LTNP versus NP, and the expression and phosphorylation states of key regulators were further validated by immunoassay. For instance, (1) SAMH1, a potent and "hot" molecule facilitating HIV-1 defense, was for the first time found elevated in LTNP compared with NP or healthy controls; elevated proteins from IFN-α response pathway may also contribute to viral control in LTNP; (2) decreased proapoptotic protein ASC along with the elevation of antiapoptotic proteins may contribute to the less apoptotic profile in PBMC of LTNP; and (3) elevated actin polymerization and less microtubule assembly that impede viral protein transport were first observed in LTNP. These results not only enhanced the understanding of the mechanisms for nonprogression of LTNP, but also may afford highly valuable clues to direct therapeutic efforts. Moreover, this work also demonstrated the ion-current-based MS1 approach as a reliable tool for large-scale clinical research.


[Short-term clinical follow-up of metal-on-metal hip resurfacing arthroplasty].
To evaluate the short-term outcome of patients receiving metal-on-mental hip resurfacing arthroplasty and analyze the factors affecting the result. In 13 patients receiving metal-on-metal hip resurfacing arthroplasties with scheduled follow-up, the treatment outcomes were assessed according to the Harris Hip Score. The short-term outcomes of hip resurfacing arthroplasties were encouraging, and intraoperative complications, infections, peripheral nerve palsy, hip dislocations or clinically overt lower limb deep vein thrombosis occurred in none of these cases. All the patients reported complete or major pain relief. Clinical assessment according to the Harris Hip Score revealed an improvement from an average score of 36.69 preoperatively to 89.63 after the surgery. Crutch use lasted for a maximum of 4 weeks postoperatively in these patients, after which the patients were all capable of walking without crutches with full weight-bearing.


Prognostic factors for recurrence of bile duct stones after endoscopic treatment by sphincter dilation.
The long-term outcome for patients after endoscopic sphincter of Oddi dilation is poorly documented. This study investigates the recurrence rate for bile duct stones in patients followed for 1 year or more after endoscopic sphincter dilation and stone extraction, and assessed prognostic factors associated with recurrence of ductal calculi. A total of 169 patients with bile duct stones were treated with endoscopic sphincter dilation between July 1998 and August 2001. Follow-up studies consisted of periodic biochemical tests and out-patient evaluations with endoscopic retrograde cholangiography or magnetic resonance cholangiography performed when follow-up exceeded 1 year. Putative risk factors for stone recurrence included gender, age, stone size and number, associated peripapillary diverticulum, gallbladder status, color of bile duct stones, and bile duct diameter. Statistical analysis consisted of both a Kaplan-Meier estimation and a multivariate Cox regression model. Complete stone clearance was achieved in 162 (95.8%) patients, of whom 151 were followed (13 patients died from unrelated disorders). Mean follow-up was 23 months. Stone recurrence was documented in 13 patients. Patients with dilated bile duct or peripapillary diverticulum were at high risk for recurrence. The interval between treatment of bile duct stones by endoscopic sphincter dilation and the recurrence of biliary calculi is relatively short. Bile duct size and peripapillary diverticula are risk factors for early recurrence.


Sociocultural influences on strategies to lose weight, gain weight, and increase muscles among ten cultural groups.
This study determined how sociocultural messages to change one's body are perceived by adolescents from different cultural groups. In total, 4904 adolescents, including Australian, Chilean, Chinese, Indo-Fijian, Indigenous Fijian, Greek, Malaysian, Chinese Malaysian, Tongans in New Zealand, and Tongans in Tonga, were surveyed about messages from family, peers, and the media to lose weight, gain weight, and increase muscles. Groups were best differentiated by family pressure to gain weight. Girls were more likely to receive the messages from multiple sociocultural sources whereas boys were more likely to receive the messages from the family. Some participants in a cultural group indicated higher, and others lower, levels of these sociocultural messages. These findings highlight the differences in sociocultural messages across cultural groups, but also that adolescents receive contrasting messages within a cultural group. These results demonstrate the difficulty in representing a particular message as being characteristic of each cultural group.


The Odds of Success: Predicting Registered Health Information Administrator Exam Success.
The purpose of this study was to craft a predictive model to examine the relationship between grades in specific academic courses, overall grade point average (GPA), on-campus versus online course delivery, and success in passing the Registered Health Information Administrator (RHIA) exam on the first attempt. Because student success in passing the exam on the first attempt is assessed as part of the accreditation process, this study is important to health information management (HIM) programs. Furthermore, passing the exam greatly expands the graduate's job possibilities because the demand for credentialed graduates far exceeds the supply of credentialed graduates. Binary logistic regression was utilized to explore the relationships between the predictor variables and success in passing the RHIA exam on the first attempt. Results indicate that the student's cumulative GPA, specific HIM course grades, and course delivery method were predictive of success.


Endogenous CHRNA7-ligand SLURP1 as a potential tumor suppressor and anti-nicotinic factor in pancreatic cancer.
Smoking is associated with increased risk and poorer prognosis of pancreatic ductal adenocarcinoma (PDAC). Nicotine acts through cholinergic nicotinic receptors, preferentially α7 (CHRNA7) that also binds the endogenous ligand SLURP1 (Secreted Ly-6/uPAR-Related Protein 1). The clinical significance of SLURP1 and its interaction with nicotine in PDAC are unclear. We detected similar levels of SLURP1 in sera from healthy donors and patients with chronic pancreatitis or PDAC; higher preoperative values were associated with significantly better survival in patients with resected tumors. Pancreatic tissue was not a source of circulating SLURP1 but contained diverse CHRNA7-expressing cells, preferentially epithelial and immune, whereas stromal stellate cells and a quarter of the tumor cells lacked CHRNA7. The CHRNA7 mRNA levels were decreased in PDAC, and CHRNA7high-PDAC patients lived longer. In CHRNA7high COLO357 and PANC-1 cultures, opposing activities of SLURP1 (anti-malignant/CHRNA7-dependent) and nicotine (pro-malignant/CHRNA7-infidel) were exerted without reciprocally interfering with receptor binding or downstream signaling. These data suggested that the ligands act independently and abolish each other's effects through a mechanism resembling functional antagonism. Thus, SLURP1 might represent an inborn anti-PDAC defense being sensitive to and counteracting nicotine. Boosting SLURP1-CHRNA7 interaction might represent a novel strategy for treatment in high-risk individuals, i.e., smokers with pancreatic cancer.


Effect of the type of silage on milk yield, intake and rumen metabolism of dairy cows grazing swards with low herbage mass.
The aim of this study was to evaluate the effect of herbage allowance (HA) and type of silage supplemented (TS) on milk yield, dry matter intake (DMI) and metabolism of dairy cows in early lactation. Thirty-six Holstein-Friesian dairy cows were allocated to four treatments derived from an arrangement of two HA (LHA = 17 or HHA = 25 kg of DM/cow/day) and two TS (grass (GS) or maize (MS)). Herbage allowance had no effect on DMI or milk yield. Rumen pH and NH3 -N concentration were not affected by HA. The efficiency of microbial protein synthesis in the rumen (microbial protein (MP)) was affected by HA with 21.5 and 23.9 g microbial nitrogen per kg ruminal digestible organic matter for LHA and HHA, respectively (P < 0.05). Supplementation with MS showed higher values of milk yield by 2.4 kg/cow/day (P < 0.001), milk protein content by 0.10 % (P < 0.023) and herbage DMI by 2.2 kg/cow/day, and showed lower values for milk urea compared to GS (P < 0.001). The former results suggest that TS had a greater effect on milk yield, total feed intake and energy intake than increase in herbage allowance; however, increase in HA had greater effects on MP than TS.


(99m)Tc-HmPAO single photon emission tomography, magnetic resonance proton spectroscopy and neuropsychological testing in evaluation of carbon monoxide neurotoxicity.
There were 10 acutely CO poisoned study patients without CNS history (head traumas, epilepsy, dementia, migraine or alcoholic diseases) in whom (99m)Tc-HmPAO SPET, HMRS and neuropsychological testing were performed. 99mTc-HmPAO SPET and neuropsychological testing were performed twice: in acute phase and at six months post CO exposure. HMRS was carried out at 8 months post CO exposure. A multidimensional analysis of variance (MANOVA) was used to statistical analysis. Regional CBF disturbances in acute phase of CO poisoning were observed in frontal cortex, basal ganglia and parietal cortex respectively. The most reversible, as seen in control (99m)Tc-HmPAO SPET examination, were the changes observed in parietal cortex. Diffuse generalized cortex hypoperfusion, both in acute phase and at 6 months post exposure, was seen only in one the patient. In all of the examined patients different elevation in mobile lipid or/and lactate concentration in frontal lobe or/and basal ganglia was revealed by HMRS evaluation at eight months post acute CO exposure. Results of neuropsychological testing at baseline and at 6 months partially correlated with neuro-imagine techniques applied.


Clinical and cytogenomic findings in OAV spectrum.
The oculoauriculovertebral spectrum (OAVS) is characterized by anomalies involving the development of the first and second pharyngeal arches during the embryonic period. The phenotype is highly heterogeneous, involving ears, eyes, face, neck, and other systems and organs. There is no agreement in the literature for the minimum phenotypic inclusion criteria, but the primary phenotype involves hemifacial microsomia with facial asymmetry and microtia. Most cases are sporadic and the etiology of this syndrome is not well known. Environmental factors, family cases that demonstrate Mendelian inheritance, such as preauricular appendages, microtia, mandibular hypoplasia, and facial asymmetry; chromosomal abnormalities and some candidate genes suggest a multifactorial inheritance model. We evaluated clinical, cytogenomic and molecularly 72 patients with OAVS, and compared our findings with patients from the literature. We found 15 CNVs (copy number variations) considered pathogenic or possibly pathogenic in 13 out of 72 patients. Our results did not indicated a single candidate genomic region, but recurrent chromosomal imbalances were observed in chromosome 4 and 22, in regions containing genes relevant to the OAVS phenotype or related to known OMIM diseases suggesting different pathogenic mechanisms involved in this genetically and phenotypic heterogeneous spectrum.


Cell-generated forces influence the viability, metabolism and mechanical properties of fibroblast-seeded collagen gel constructs.
The aim of this study was to investigate the influence of the endogenous forces generated by fibroblast-mediated contraction, using four individual collagen gel models that differed with respect to the ability of the cells to contract the gel. Human neonatal dermal fibroblasts were seeded in type I collagen and the gels were cast in a racetrack-shaped mould containing a removable central island. Two of the models were mechanically stressed (20 mm and 10 mm), as complete contraction was prevented by the presence of a central island. The central island was removed in the third model (released) and the final model was cast in a Petri dish and detached, allowing full multi-axial contraction (SR). Cell viability was maintained in the 10 mm, released and SR models over a 6 day culture period but localized regions of cell death were evident in the 20 mm model. Cell and collagen alignment was developed in the 20 mm and 10 mm models and to a lesser extent in the released model, but was absent in the SR model. Cell proliferation and collagen synthesis was lower in the 20 mm model compared to the other systems and there was evidence of enhanced matrix metalloproteinase production. The mechanical properties of the 20 mm model system were inferior to the 10 mm and released systems. The 10 mm model system induced a high level of cell and matrix orientation and may, therefore, represent the best option for tissue-engineered ligament repair involving an orientated fibroblast-seeded collagen gel.


Modulation of voltage-gated Ca2+ current in vestibular hair cells by nitric oxide.
The structural elements of the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathway have been described in the vestibular peripheral system. However, the functions of NO in the vestibular endorgans are still not clear. We evaluated the action of NO on the Ca(2+) currents in hair cells isolated from the semicircular canal crista ampullaris of the rat (P14-P18) by using the whole cell and perforated-cell patch-clamp technique. The NO donors 3-morpholinosydnonimine (SIN-1), sodium nitroprusside (SNP), and (+/-)-(E)-4-ethyl-2-[(Z)-hydroxyimino]-5-nitro-3-hexen-1-yl-nicotinamide (NOR-4) inhibited the Ca(2+) current in hair cells in a voltage-independent manner. The NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO) prevented the inhibitory effect of SNP on the Ca(2+) current. The selective inhibitor of the soluble form of the enzyme guanylate cyclase (sGC), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), also decreased the SNP-induced inhibition of the Ca(2+) current. The membrane-permeant cGMP analogue 8-Br-cGMP mimicked the SNP effect. KT-5823, a specific inhibitor of cGMP-dependent protein kinase (PGK), prevented the inhibition of the Ca(2+) current by SNP and 8-Br-cGMP. In the presence of N-ethylmaleimide (NEM), a sulfhydryl alkylating agent that prevents the S-nitrosylation reaction, the SNP effect on the Ca(2+) current was significantly diminished. These results demonstrated that NO inhibits in a voltage-independent manner the voltage-activated Ca(2+) current in rat vestibular hair cells by the activation of a cGMP-signaling pathway and through a direct action on the channel protein by a S-nitrosylation reaction. The inhibition of the Ca(2+) current by NO may contribute to the regulation of the intracellular Ca(2+) concentration and hair-cell synaptic transmission.


Essential factors in the implementation of an Expanded Program on Immunization in an urban-periurban community in Nigeria.
The aim of this study was to identify some of the factors that affected the implementation of the Expanded Program on Immunization (EPI) in the Local Government Area (LGA). The study covered the three communities in Calabar LGA. Data on vaccine-eligible children and pregnant women were sought with questionnaires; other information on technical and community aspects of the EPI was gathered with specially designed checklists. EPI coverage for most antigens increased between 70-100% in response to highly-organized immunization campaigns initiated in 1985. In subsequent years, up to 1989, similar campaign-induced responses to national, state and local campaign efforts were observed. In contrast, coverage levels attributable to routine immunization remained unsatisfactory. When tested with the Z-statistic using 1985 as the base year (p < 0.05), there was a significant difference between the proportion of eligible children and pregnant women who did not receive their full dose of immunization. Socio-logistic variables found to be important in EPI implementations included scheduling, health staff attitude, intersectoral collaboration, and health education. Lack of community participation was also found to be a crucial constraining factor. As community participation/involvement is critical in sustaining health programs, social marketing techniques are suggested for future use.


Biofabrication of Gold Nanoparticles Using Capsicum annuum Extract and Its Antiquorum Sensing and Antibiofilm Activity against Bacterial Pathogens.
The intensive use of antimicrobial agents has led to the emergence of multidrug resistance (MDR) among microbial pathogens. Such microbial (MDR) infections become more problematic in chronic diseases in which the efficacy of chemotherapeutic agents is highly reduced. To combat the problem of drug resistance, inhibition of bacterial quorum sensing (QS) and biofilms are considered as promising strategies in the development of anti-infective agents. In this study, gold nanoparticles (AuNPs-CA) were biofabricated using Capsicum annuum aqueous extract and characterized. The AuNPs-CA were tested against the QS-controlled virulence factors and biofilms of Pseudomonas aeruginosa PAO1 and Serratia marcescens MTCC 97. AuNPs-CA were found to be crystalline in nature with average particle size 19.97 nm. QS-mediated virulent traits of P. aeruginosa PAO1 such as pyocyanin, pyoverdin, exoprotease activity, elastase activity, rhamnolipids production, and swimming motility were reduced by 91.94, 72.16, 81.82, 65.72, 46.66, and 46.09%, respectively. Similarly, dose-dependent inhibition of virulence factors of S. marcescens MTCC 97 was recorded by the treatment of AuNPs-CA. The biofilm development and exopolysaccharide (EPS) production also decreased significantly. Microscopic analysis revealed that the adherence and colonization of the bacteria on solid support were reduced to a remarkable extent. The findings indicate the possibility of application of green synthesized gold nanoparticles in the management of bacterial infection after careful in vivo investigation.


Experimental pleurodesis induced by antibiotics (macrolides or quinolones).
Chemical pleurodesis is a therapeutic tool for the treatment of recurrent pleural effusions, mainly those of neoplastic etiology. In the past, tetracycline was the sclerosant agent of choice in clinical practice, but presently, there is no consensus about an ideal agent. The aim of this study was to evaluate the effectiveness of macrolides (azithromycin and clarithromycin) or quinolones (levofloxacin and gatifloxacin) in inducing experimental pleurodesis in rabbits. Forty New Zealand rabbits randomized into groups of 10 received (at a total volume of 2 mL for each animal) 1 of the 4 drugs by intrapleural injection. After 28 days, the animals were euthanized and the pleural cavity was evaluated macroscopically and microscopically. The intensity of the macroscopic adhesions was mild in all groups. On microscopic analysis, minimal pleural fibrosis and inflammation were observed in all animals. The macrolides (azithromycin or clarithromycin) and the quinolones (levofloxacin or gatifloxacin) when injected into the normal pleural space of rabbits are not effective in promoting pleurodesis. Additional research is required to identify sclerosing agents capable of inducing pleurodesis.


Operando Soft X-ray Absorption Spectroscopic Study on a Solid Oxide Fuel Cell Cathode during Electrochemical Oxygen Reduction.
An operando soft X-ray absorption spectroscopic technique, which enabled the analysis of the electronic structures of the electrode materials at elevated temperature in a controlled atmosphere and electrochemical polarization, was established and its availability was demonstrated by investigating the electronic structural changes of an La2 NiO4+δ dense-film electrode during an electrochemical oxygen reduction reaction. Clear O K-edge and Ni L-edge X-ray absorption spectra could be obtained below 773 K under an atmospheric pressure of 100 ppm O2 /He, 0.1 % O2 /He, and 1 % O2 /He gas mixtures. Considerable spectral changes were observed in the O K-edge X-ray absorption spectra upon changing the PO2 and application of electrical potential, whereas only small spectral changes were observed in Ni L-edge X-ray absorption spectra. A pre-edge peak of the O K-edge X-ray absorption spectra, which reflects the unoccupied partial density of states of Ni 3d-O 2p hybridization, increased or decreased with cathodic or anodic polarization, respectively. The electronic structural changes of the outermost orbital of the electrode material due to electrochemical polarization were successfully confirmed by the operando X-ray absorption spectroscopic technique developed in this study.


Initial experience with in-vitro fertilization technology in the English-speaking Caribbean.
This audit documents the first experience with in-vitro Fertilization technology in the English-speaking Caribbean. From 1996 to 2000, 121 cycles have been performed in 99 couples utilizing these techniques. After ovarian stimulation, 1,103 oocytes were retrieved (average 9.1) and of these, 65% fertilized normally, with embryo transfer possible in 111 cycles. Twenty-one pregnancies were recorded (21.2% per patient and 18.9% per embryo transfer) and the live birth rate per patient was 12.1%. The trend was for the success rate to be better in patients under age 36 years.


Acute compartment syndrome of the triceps and deltoid.
Compartment syndrome is a condition in which the circulation and function of tissues within a closed space are compromised by increased pressure within that space. We report on the rare occurrence of compartment syndrome of the upper arm and deltoid in a professional power-lifter. This case stresses the importance of heightened awareness and expedient measures to prevent ischemic muscle necrosis and nerve injury.


The question of a right to life in animal ethics.
In animal ethics a Right to Life has been postulated repeatedly, but no valid argument has been produced yet. Thus the question of a Right to Life in animal ethics remains unanswered. It is remarkable that no philosopher has yet found a valid argument against Epicurus (there is nothing fearful in the absence of life). On the other hand, there is, again based upon Epicurus' argument, a basic moral duty with respect to painless killing (i.e. no fear, no distress, no suffering).


Hypertension and obstructive sleep apnea in Caucasian children.
To evaluate the prevalence of hypertension and/or left ventricular hypertrophy (LVH) in children with a diagnosis of obstructive sleep apnea (OSA). A cross-sectional case series of consecutive, otherwise healthy children aged > 4 years, with polysomnography-proven OSA [apnea hypopnea index (AHI) > 1.5/h] is described. Echocardiography was performed on all subjects and left ventricular mass was calculated. Study subjects underwent additional investigation with 24-h ambulatory blood pressure (BP) monitoring. Thirty children (21 males) were studied. Mean age was 8.9 years. Mean body mass index was 19.87 kg/cm(2). Mean AHI was 14.3/h. 10/30 (33%) of the study population met criteria for pre-hypertension (n = 3) or masked hypertension (n = 7) based on standard ambulatory monitoring criteria. All 10 children had systolic hypertension throughout the night with 5 of these also having elevated daytime systolic readings. There was a relationship between AHI and BP showing an increase of 1.162 percentile units in mean diastolic night BP (age, gender and height specific) per unit increase in AHI (P = 0.018). There were no subjects with LVH and/or right ventricular hypertrophy. In our population of otherwise healthy Caucasian children, there was a high prevalence of hypertension that would not have been identified using standard office/clinic protocols.