[Comparison of the therapeutic effectiveness of selected cholinesterase reactivators with atropine in acute fosdrine poisoning in mice].
In experiments on male mice, the effect of the cholinesterase reactivators obidoxime, methoxime and HI-6 in combination with atropine sulfate on the acute intoxication with the organophosphorous insecticide fosdrine was tested in dependence on the period of administration of drugs after intoxication and on the dose of oxime by influencing the LD50 value in 48-hour survival of experimental animals. It has been demonstrated that the rate of the therapeutic intervention is a much more important factor influencing the effect of oximes than the dose of oximes. A shortening of the period of drug administration from 2 minutes to 30 seconds substantially increases the effects of all three oximes. A comparison of the effects of all three reactivators has shown that the oxime HI-6 is significantly more effective than the remaining two reactivators in the case of therapy of intoxication 30 seconds after the application of the noxa. In the therapy of intoxication 2 minutes after the exposure of experimental animals to fosdrine, the effect of the antidotal therapy was relatively low regardless of the selected oxime.


[Analysis on Diversity of Plankton Microbial Community in the Beijing-Tianjin-Hebei Section of the North Canal River].
Reclaimed water plays an important role in alleviating the shortage of urban water resources; however, the trace pollutants and pathogens in reclaimed water have an effect on the plankton community in the receiving water. This study investigated the spatial variation mechanism of microbial community diversity in the Beijing-Tianjin-Hebei reach of the Nordkanal River based on the OTUs and phylum level fragment number and fragment abundance data matrix. The results showed that the physical and chemical disturbance caused by the frequent inflow of reclaimed water changed the hydrology and water quality of the water body, and the plankton community could be divided into two different groups along the geographical scale:the medium and upstream clustering (MUC) and the downstream clustering (DC). The analysis of diversity index based on the OTUs data matrix showed that the species diversity of the DC group was significantly higher than that of the MUC group, and the abundance distribution and evenness showed the opposite trend. The species richness was mainly determined by the fragment diversity of the occasional microflora; the evenness was mainly determined by the variation of the abundance of the dominant microflora; the sensitivity of the subcommunity structure with different abundance levels to spatial change was in the order of non-dominant microflora > occasional microflora > dominant microflora. The diversity analysis of the data matrix based on phylum level also showed that the species diversity of the DC group was significantly higher than that of the MUC group, and the change trend of abundance was the opposite; the most sensitive microflora group was the non-dominant phyla, followed by the occasional phyla, and the dominant phyla group was the least sensitive. The data matrix based on the number of level segments of the gate was more sensitive to environmental changes than the multi-degree data matrix based on the level of the gate. The environmental factors significantly related to microbial community were turbidity; permanganate index; oxidation-reduction potential (ORP); macrolide (MLs); tetracycline antibiotic (TCs); and regional response factors of salt ions, carbon, and inorganic nitrogen. In the aspect of abundance and diversity, these phylas that the DC group was significantly more than the MUC group were more significantly negatively correlated with MLs, whereas they were positively correlated with TCs, and these phylas that the MUC group was significantly more than the DC group was more significantly positively correlated with MLs. The research results can provide a theoretical basis and technical guidance for the ecological rehabilitation of urban river courses with reclaimed water as their main water supply source.


Systematic review and meta-analyses on the effects of whole-body vibration on bone health.
To determine whole body vibration influence on human bone density and bone biomarkers. We identified studies in Medline, Web of Science, Cumulative Index of Nursing and Allied Health, SPORTDiscus, Embase and Cochrane from inception to November 2021. Human randomized controlled trials involving commercially available whole body vibration platforms were included. Outcomes included bone density mean difference and serum concentrations of biomarkers (Procollagen type 1 N-terminal Propeptides, Osteocalcin, Bone specific alkaline phosphatase, and C-terminal Telopeptide of type 1 collagen). Random effects model (Hedges' g effect-size metric and 95% confidence-intervals) compared whole body vibration effect on bone density and bone biomarkers. Moderator analyses assessed health status, age, menopausal status, vibration type, vibration frequency, and study duration influence. Meta-analysis of 30 studies revealed bone density improvement after whole body vibration (Hedges' g = 0.11; p = 0.05; 95% CI = 0.00, 0.22). Whole body vibration improved bone density in healthy (Hedges' g = 0.10; p = 0.01; 95% CI = 0.02, 0.17) and postmenopausal women (Hedges' g = 0.09; p = 0.02; 95% CI = 0.01, 0.18). Bone density also increased following side-alternating whole body vibration intervention (Hedges' g = 0.21; p = 0.02; 95% CI = 0.04, 0.37). Whole body vibration had no significant effect on either bone formation biomarkers (Hedges' g = 0.22; p = 0.01; 95% CI = 0.05, 0.40) or bone resorption biomarkers (Hedges' g = 0.03; p = 0.74; 95% CI = -0.17, 0.23). Whole body vibration may be clinically useful as non-pharmacological/adjunct therapy to mitigate osteoporosis risk in healthy postmenopausal females. Additional studies are needed to determine the underlying mechanisms.


Psychiatric genetics: the case of single gene disorders.
Quantitative and molecular genetics have made important developments in the last three decades. There is increasing evidence of the role of heredity in the field of neuropsychiatric disorders in children. So far, only a few pathways between genes and behaviour have been unravelled. Quantitative genetics puts polygenic inheritance models forward. Molecular genetic research based on these models seems promising, but until now has provided only a limited explanation for the variance in the studied neuropsychiatric disorders. In these models the complexity of the expression of a single gene grows exponentially with the number of genes involved. Consequently, research on the gene-phenotype relationships and phenotypical variability in such models is extremely complex.The candidate gene approach, in which the gene-phenotype pathway of a single gene is studied, is more manageable, and in our opinion essential in understanding multiple gene models. We discuss recent findings in the field and their relevance for neuropsychiatric phenotypes. Single gene defects will only explain a part of the range of neuropsychiatric disorders in children, but the evidence that this approach can generate may help to clarify neuropsychiatric phenotypes. The discovery of single gene disorders in subgroups of subjects with a neuropsychiatric phenotype may result in new perspectives for their treatment.


Trapped between drowning and desiccation: Riverine plants under hydropeaking.
Hydropeaking is part of hydropower production. The discontinuous release of turbined water during hydropeaking generates sudden rise and falls of the water levels, as well as extended droughts. These artificial flow fluctuations impose challenging growing conditions for riverine vegetation. In order to identify vulnerable/resistant plant species to hydropeaking and to evaluate the impact of contrasting hydropeaking scenarios (simplified (i.e., sudden deep floods, frequent soil saturation and drought) and real-life, power plant-induced scenarios), we measured germination, survival, and morphological and physiological attributes of a selection of 14 plant species commonly found along riparian areas. Species were subject to different hydropeaking scenarios during three months (vegetative period) in the field and in a greenhouse. Half of the species performed worse under hydropeaking in comparison to the control (e.g., less germination and biomass, lower growth rates, reduced stem and root length, physiological stress) but none of the tested hydropeaking scenarios was clearly more disruptive than others. Betula pubescens, Alnus incana and Filipendula ulmifolia showed the largest vulnerability to hydropeaking, while other species (e.g., Carex acuta) were resistant to it. Both in the field and in the greenhouse, plants in perturbed scenarios accumulated more 13C than in the control scenario indicating limited capacity to perform 13C isotope discrimination and evidencing plant physiological stress. The highest 13C abundances were found under drought or flooding conditions in the greenhouse, and under the highest hydropeaking intensities in the field (e.g., Betula pubescens). Our results suggest that any hydropeaking scheme can be equally detrimental in terms of plant performance. Hydropeaking schemes that combine periods of severe drought with long and frequent flooding episodes may create a hostile environment for riverine species. Further research on "hydropeaking-tolerant" plant traits is key to draw the boundaries beyond which riverine species can germinate, grow and complete their life cycle under hydropeaking.


Truncated forms of the androgen receptor are associated with polyglutamine expansion in X-linked spinal and bulbar muscular atrophy.
X-linked spinal and bulbar muscular atrophy (SBMA) is a rare form of motor neuron degeneration linked to a CAG repeat expansion in the first exon of the androgen receptor gene coding for a polyglutamine tract. In order to investigate the properties of the SBMA androgen receptor in neuronal cells, cDNAs coding for a wild-type (19 CAG repeats) and a SBMA mutant androgen receptor (52 CAG repeats) were transfected into mouse neuroblastoma NB2a/d1 cells. The full length androgen receptor proteins, of 110-112 kDa and 114-116 kDa for the wild-type and mutant protein, respectively, were detected by Western blotting in transfected cells. In addition, the presence of an expanded polyglutamine tract in the SBMA androgen receptor appears to enhance the production of C-terminally truncated fragments of the protein. A 74 kDa fragment was particularly prominent in cells expressing the SBMA androgen receptor. From its size, it can be deduced that the 74 kDa fragment lacks the hormone binding domain but retains the DNA binding domain. The 74 kDa fragment may therefore be toxic to motor neurons by initiating the transcription of specific genes in the absence of hormonal control. Immunofluorescence microscopy on transfected NB2a/d1 cells showed that, after hormone activation, the wild-type androgen receptor translocated to the nucleus whereas the SBMA androgen receptor was mainly localized in the cytoplasm in the form of dense aggregates with very little androgen receptor protein in the nucleus. This could explain the reduction in transcriptional activity of the SBMA mutant as compared with wild-type androgen receptor.


[Genetic analysis and gene mapping of DDF1, a pleiotropic gene involving in both vegetable and reproductive growth in rice].
There are many pleiotropic genes playing key roles in regulating both vegetative growth and reproductive development in plants. A dwarf mutant of rice with deformed flowers, named as ddf1, was identified from indica rice breeding lines. Genetic analysis indicated that ddf1 was resulted from the recessive mutation of a single gene, temporarily named as DDF1. This result suggested that DDF1 is a pleiotropic gene, which controls both vegetative growth and reproductive development in rice. To map this gene, an F2 population was developed by crossing the ddf1 heterozygote with the tropical japonica rice variety DZ60. By means of bulked segregant analysis and small population-based linkage analysis using the published RM-series rice SSR markers, DDF1 was preliminarily mapped in a region between markers RM588 and RM587 on chromosome 6 with the genetic distances of 3.8 cM and 2.4 cM to the two markers, respectively. By developing new SSR markers in this interval according to the published rice genome sequence, we further mapped DDF1 in a 165 kb interval. The results will facilitate cloning of DDF1.


[Contribution to the mechanism of the "factor VIII bypassing activity" (FEIBA)-reaction].
The principle of the FEIBactivity hadn't been defined in a sufficient manner up to now. Probably the factor VII or factor VIIa are playing a key role. According to own experiments the factor VII activity increases considerably in activated prothrombincomplex concentrates together with the quotient factor VIIa/VII. Factor VII should be administered in his activated form for bypassing. Fractions with limitation of the activation process to factor VII are of a low thrombogenicity. Among activated coagulation factors factor VIIa persists longest in the circulation and a bypass efficacy can be provoked only by this.


Victimization of the mentally ill: an unintended consequence of deinstitutionalization.
Twenty years ago, legal interventions and dramatic advancements in psychopharmacology provided the impetus for a mass exodus from public mental health institutions to community settings. This well-intended move was predicated on the development of a community mental health center network. An unintended consequence, however, is that many deinstitutionalized mentally ill clients have been forced onto the street with little or no treatment. Moreover, a new wave of never treated youth and elderly have joined the street subculture. Without adequate clinical treatment, these people are vulnerable to victimization and to arrest and incarceration. In this article, the history of the problem is reviewed and steps to create a more responsive clinical network to cope with the problem are discussed.


Protein analysis of laser capture micro-dissected tissues revealed cell-type specific biological functions in developing barley grains.
Both the nucellar projection (NP) and endosperm transfer cells (ETC) of the developing barley grain (harvested 8 days after flowering) were isolated by laser capture micro-dissection combined with pressure catapulting. Protein extracts were analyzed by nanoUPLC separation combined with ESI-Q-TOF mass spectrometry. The majority of the ~160 proteins identified were involved in translation, protein synthesis, or protein destination. The NP proteome was enriched for stress defense molecules, while proteins involved in assimilate transport and the mobilization of nutrients were common to both the NP and the ETC. The combined qualitative and quantitative protein profiling allowed for the identification of several proteins showing tissue specificity in their expression, which underlines the distinct biological functions of these two tissues within the developing barley grain.


Environmental, policy, and cultural factors related to physical activity among rural, African American women.
Sixty-one African American women (ages 20-50 years) from a rural community in Alabama participated in six focus groups. Barriers to and enablers of physical activity were identified and grouped into personal, environmental (social and physical), policy, and cultural themes for qualitative analyses. Personal factors included motivation, perceived health, feeling tired, and lack of time; social environmental factors included support from friends, family, and issues related to child care; physical environmental factors included weather, access to facilities, availability of sidewalks or other places to walk; policy factors included personal safety concerns (loose dogs, traffic, etc.) and inflexible work environments. Some, but not all, women perceived cultural differences as a factor affecting physical activity levels. Differences in socioeconomic levels and time demands among women of different cultures were identified as factors that may influence physical activity. Participants provided suggestions for community-based physical activity interventions using an environmental approach.


Maternal XTcf1 and XTcf4 have distinct roles in regulating Wnt target genes.
Wnt signaling pathways have essential roles in developing embryos and adult tissue, and alterations in their function are implicated in many disease processes including cancers. The major nuclear transducers of Wnt signals are the Tcf/LEF family of transcription factors, which have binding sites for both the transcriptional co-repressor groucho, and the co-activator beta-catenin. The early Xenopus embryo expresses three maternally inherited Tcf/LEF mRNAs, and their relative roles in regulating the expression of Wnt target genes are not understood. We have addressed this by using antisense oligonucleotides to deplete maternal XTcf1 and XTcf4 mRNAs in oocytes. We find that XTcf1 represses expression of Wnt target genes ventrally and laterally, and activates their expression dorsally. Double depletions of XTcf1 and XTcf3 suggest that they act cooperatively to repress Wnt target genes ventrally. In contrast, XTcf4 has no repressive role but is required to activate expression of Xnr3 and chordin in organizer cells at the gastrula stage. This work provides evidence for distinct roles for XTcfs in regulating Wnt target gene expression.


The publication outcome for the papers presented at the 1990 ABA conference.
This retrospective review of the 1990 ABA orally presented abstracts found an overall publication rate of slightly more than 26%. This included both same-content and related-content publications. When the abstracts were made a subset by theme, a major variance in the publication rates was found. Abstracts that had a psychologic content (72.73%), for example, fared much better than reports of in vitro research (6.9%). This overall rate when compared to publication studies in other clinical areas was found to be quite low. This study further found that there was a great deal of similarity between abstracts that were published and those that were not. The one meaningful predictor of ultimate journal publication was the clarity of the presentation of statistically related information.


A general model of drug prescription.
Currently, there is no widely accepted structured representation of drug prescription. Nevertheless, a structured representation is required for entering and storing drug prescriptions avoiding free text in computerized systems, and for drug prescription reviews. Derived from part of the work of the European OPADE project, we describe an object-oriented model of drug prescription which incorporates important concepts such as the phase and triggering event concepts. This model can be used to record all drug prescriptions, including infusions, in a structured way avoiding free text. The phase concept allows the storage of sequentially ordered dosage regimens for a drug within the same prescription. The prescription triggering event concept allows recording of the administration of a drug conditional to dates, symptoms and clinical signs, medical procedures, and everyday life events. This model has been implemented within the OPADE project; the corresponding aspects of the user interface are presented to show how this model can be used in practice. Even if other new attributes may be added to the described objects, the structure of this model is suitable for general use in software which requires the entry, storage and processing of drug prescriptions.


Resolution of stroke deficits following contralateral grafts of conditionally immortal neuroepithelial stem cells.
Grafts of MHP36 cells have previously been shown to reduce dysfunction after global ischemia in rats. To test their efficacy after focal ischemia, MHP36 cells were grafted 2 to 3 weeks after transient intraluminal middle cerebral artery occlusion (tMCAO) in rats. MHP36 cells were implanted into the hemisphere contralateral to the lesion, with 8 deposits of 3 microL of cell suspension (25 000 cells per microliter). Sham grafted rats received equivalent volumes of vehicle. Three groups, sham-operated controls (n=11), MCAO+sham grafts (n=10), and MCAO+MHP36 grafts (n=11), were compared in 3 behavioral tests. In the bilateral asymmetry test, MCAO+MHP36 grafted rats exhibited neglect before grafting but subsequently showed no significant dysfunction, whereas MCAO+sham grafted rats showed stable sensorimotor deficits over 18 weeks relative to controls. MCAO+sham grafted rats demonstrated spontaneous motor asymmetry and increased rotational bias after injection of dopamine agonists. MCAO+MHP36 and control groups exhibited no bias in either spontaneous or drug-induced rotation. In contrast to motor recovery, MCAO+MHP36 grafted rats showed no improvement relative to MCAO+sham grafted rats in spatial learning and memory in the water maze. MCAO produced large striatal and cortical cavitations in both occluded groups. Lesion volume was significantly reduced (P<0.05) in the MCAO+MHP36 grafted group. The majority of MHP36 cells were identified within the intact grafted hemisphere. However, MHP36 cells were also seen in the cortex, striatum, and corpus callosum of the lesioned hemisphere. MHP36 cells may improve functional outcome after MCAO by assisting spontaneous reorganization in both the damaged and intact hemispheres.


Predictive value of CA 125 for ovarian carcinoma in patients presenting with pelvic masses.
Between November 1984 and May 1986, 56 patients presenting with a pelvic mass to the Gynecologic Oncology Service of McMaster University and the Hamilton Regional Oncology Center underwent laparotomy for possible ovarian cancer. All patients had blood drawn for CA 125 three days before operation. Levels above 35 U/mL were considered positive; CA 125 had a positive predictive value of 60%. False positives occurred in patients with nongynecologic malignancies and with benign gynecologic conditions. On the other hand, CA 125 had a negative predictive value of 100%, suggesting that this test may be useful in identifying those patients with pelvic masses at higher risk for malignancy, who may require transfer for surgery at a tertiary care center.


A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction.
IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody-producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy-proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m2, to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8-2.4) mg/dl, and proteinuria was 2.1 (0.6-5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose-deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy.


Fabrication of a pi-phase-shifted fiber Bragg grating at twice the Bragg wavelength with the standard phase mask technique.
A pair of reflection peaks/transmission dips, at twice the Bragg wavelength, were observed in spectra of a Type I fiber Bragg grating written with the standard phase mask technique. The occurrence of two peaks/dips, rather than one, is attributed to the interleaved refractive index modulations along the fiber core, with the periodicity of the phase mask that has been observed previously in images of gratings that cause destructive interference in a reflected wave at the Bragg condition owing to the pi phase difference between the grating phases. Thus the standard phase mask technique produced an alternative type of pi-phase-shifted grating at twice the design Bragg wavelength.


Molecular mechanism of diabetic cardiomyopathy and modulation of microRNA function by synthetic oligonucleotides.
Diabetic cardiomyopathy (DCM) is a chronic complication in individuals with diabetes and is characterized by ventricular dilation and hypertrophy, diastolic dysfunction, decreased or preserved systolic function and reduced ejection fraction eventually resulting in heart failure. Despite being well characterized, the fundamental mechanisms leading to DCM are still elusive. Recent studies identified the involvement of small non-coding small RNA molecules such as microRNAs (miRs) playing a key role in the etiology of DCM. Therefore, miRs associated with DCM represents a new class of targets for the development of mechanistic therapeutics, which may yield marked benefits compared to other therapeutic approaches. Indeed, few miRs currently under active clinical investigation, with many expressing cautious optimism that miRs based therapies will succeed in the coming years. The major caution in using miRs based therapy is the need to improve the stability and specificity following systemic injection, which can be achieved through chemical and structural modification. In this review, we first discuss the established role of miRs in DCM and the advances in miRs based therapeutic strategies for the prevention/treatment of DCM. We next discuss the currently employed chemical modification of miR oligonucleotides and their utility in therapies specifically focusing on the DCM. Finally, we summarize the commonly used delivery system and approaches for assessment of miRNA modulation and potential off-target effects.


Harboring Contaminants in Repeatedly Reprocessed Pedicle Screws.
It consisted of evaluation of the pedicle screws for presence of residual nonmicrobial contaminants and tabulation of the minimum steps and time required for reprocessing implants as per guidelines and its comparison with actual practice. An evaluation of the nonmicrobial contaminants prevalent on the pedicle screws used for spine surgery and the underlying practice cause behind the source. The first component consisted of a random selection of 6 pedicle screws and its assessment using optical microscopy, scanning electron microscopy with energy dispersive spectroscopy, and Fourier transform infrared spectroscopy. The second component consisted of review of implant reprocessing guidelines and its applicability. Three types of contaminants were identified: corrosion, saccharide of unknown origin, and soap residue mixed with and were mostly present at the interfaces with low permeability. In addition, manufacturer's guideline recommends 19 hours of reprocessing, whereas the real-time observation revealed a turnaround time of 1 hour 17 minutes. Repeatedly reprocessed pedicle screws host corrosion, carbohydrate, fat, and soap, which could be a cause of surgical site infection and inflammatory responses postsurgery. The cause behind it is the impracticality of repeated cleaning and inspection of such devices.


25-Hydroxycholesterol-3-sulfate attenuates inflammatory response via PPARγ signaling in human THP-1 macrophages.
The nuclear receptor peroxisome proliferator-activated receptors (PPARs) are important in regulating lipid metabolism and inflammatory responses in macrophages. Activation of PPARγ represses key inflammatory response gene expressions. Recently, we identified a new cholesterol metabolite, 25-hydroxycholesterol-3-sulfate (25HC3S), as a potent regulatory molecule of lipid metabolism. In this paper, we report the effect of 25HC3S and its precursor 25-hydroxycholesterol (25HC) on PPARγ activity and on inflammatory responses. Addition of 25HC3S to human macrophages markedly increased nuclear PPARγ and cytosol IκB and decreased nuclear NF-κB protein levels. PPARγ response element reporter gene assays showed that 25HC3S significantly increased luciferase activities. PPARγ competitor assay showed that the K(i) for 25HC3S was ∼1 μM, similar to those of other known natural ligands. NF-κB-dependent promoter reporter gene assays showed that 25HC3S suppressed TNFα-induced luciferase activities only when cotransfected with pcDNAI-PPARγ plasmid. In addition, 25HC3S decreased LPS-induced expression and release of IL-1β. In the PPARγ-specific siRNA transfected macrophages or in the presence of PPARγ-specific antagonist, 25HC3S failed to increase IκB and to suppress TNFα and IL-1β expression. In contrast to 25HC3S, its precursor 25HC, a known liver X receptor ligand, decreased nuclear PPARγ and cytosol IκB and increased nuclear NF-κB protein levels. We conclude that 25HC3S acts in macrophages as a PPARγ ligand and suppresses inflammatory responses via the PPARγ/IκB/NF-κB signaling pathway.


Effects of cysteamine on the hypothalamic-pituitary axis in the rat.
The effects of cysteamine (CSH) on hypothalamic concentrations of neuropeptides were reviewed and correlated with available information on changes in pituitary hormone content and circulating pituitary hormone levels. In our study, we found notable changes in the morphology of lactotropes from female Long-Evans rats treated for 7 days with CSH (300 mg/(kg X day) per os). Forming granules increased in number, and crinophagy, which is the augmented incorporation of these granules into lysosomes, was evident. Storage granules were reduced in number. These changes were not suppressed by simultaneous administration of 17 beta-estradiol (50 micrograms/day s.c.) for 7 days. CSH administration failed to prevent estrogen-induced lactotrope hyperplasia. Serum prolactin levels were unaffected by CSH treatment. The morphological changes in the adenohypophysis did not resemble those observed when rats were treated with bromocriptine. The rough endoplasmic reticulum luminal density was reduced in gonadotropes from intact CSH-treated rats after 1 wk. CSH treatment suppressed the development of castration cells and significantly reduced serum luteinizing hormone levels in ovariectomized rats. The morphological effects of CSH appeared to be confined to lactotropes and gonadotropes.


Mutual transcriptional interference between RelA and androgen receptor.
Cross-modulation between androgen receptor (AR) and NF-kappaB/Rel proteins was studied using various androgen- and NF-kappaB-regulated reporter genes under transient transfection conditions. In COS-1 cells, elevated expression of RelA (p65) repressed AR-mediated transactivation in a dose-dependent manner, whereas NFkappaB1 (p50), another major member of the NF-kappaB family, did not influence transactivation. The repression of AR appeared to involve the N-terminal region of the protein between residue 297 and the DNA-binding domain. RelA-mediated transrepression could not be overcome by increasing the amount of AR. Transcriptional interference between RelA and AR was mutual in that cotransfected AR was able to attenuate transactivation by RelA in a dose- and steroid-dependent fashion. An excess of RelA was able to rescue the repression to some extent. Immunological analyses of RelA and AR protein levels indicated that transrepression was not due to reciprocal decrease in their amounts. Neither did AR increase the concentration of IkappaBalpha, which can sequester and inactivate RelA. Electrophoretic mobility shift assays using extracts from cotransfected cells and purified recombinant proteins showed that AR and RelA did not significantly influence each other's DNA binding activity. Nevertheless, protein-protein interaction experiments demonstrated a weak association between AR and RelA. Collectively, these data suggest that the mutual repression in intact cells is due to formation of AR-RelA complexes that are held together by another partner or to competition for a coactivator required for transcription.


Studies on bioaccumulation patterns, biochemical and genotoxic effects of copper on freshwater fish, Catla catla: an in vivo analysis.
During present study, the copper (Cu) mediated oxidative stress was measured that induced DNA damage by concentrating in the tissues of fish, Catla catla (14.45±1.24g; 84.68±1.45mm) (Hamilton,1822). Fish fingerlings were retained in 5 groups for 14, 28, 42, 56, 70 and 84 days of the exposure period. They were treated with 2/3, 1/3, 1/4 and 1/5 (T1-T4) of 96h lethal concentration of copper. Controls were run along with all the treatments for the same durations. A significant (p < 0.05) dose and time dependent concentration of Cu was observed in the gills, liver, kidney, muscles, and brain of C. catla. Among organs, the liver showed a significantly higher concentration of Cu followed by gills, kidney, brain, and muscles. Copper accumulation in these organs caused a significant variation in the activities of enzymes viz. superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD). The SOD activity varied significantly in response to the exposure time of Cu as 56 > 70 > 42 > 84 > 28 > 14 days while CAT activity exhibited an inverse relationship with the increase in Cu concentration. POD activity showed a significant rise with an increase in Cu exposure duration. Comet assay exhibited significant DNA damage in the peripheral erythrocytes of Cu exposed C. catla. Among four exposure concentrations, 2/3rd of LC50 (T1) caused significantly higher damage to the nuclei compared to control. Increased POD and SOD activity, as well as a decrease in CAT activity in response to Cu, demonstrates the involvement of a protective mechanism against reactive oxygen species (ROS), whereas increased ROS resulted in higher DNA damage. These above-mentioned molecular markers can be efficiently used for the biomonitoring of aquatic environments and conservation of edible fish fauna.


Aseptic loosening of 2 rim-fix, hydroxyapatite-coated acetabular cups.
Two cases of aseptic loosening in the 11th and 12th year of follow-up of the same acetabular component of a fully hydroxyapatite (HA)-coated total hip arthroplasty are presented. The acetabular cup was a rim-fix type, HA-coated, titanium hemispherical shell secured to the bony acetabulum with titanium screws at the peripheral polyethylene rim. The short-term and midterm results were good with HA-coated total hip arthroplasties, but further studies are needed to investigate whether the >10-year survival of these cups is as good as the survival of cemented ones.


Analysis of the role of the phosphate translocator and external metabolites in steady-state chloroplast photosynthesis.
The role of the phosphate translocator and the importance of the extrachloroplastic concentrations of phosphate, 3-phosphoglycerate, and dihydroxyacetone phosphate in steady-state photosynthesis is examined with a kinetic model. The steady-state stromal concentrations of these compounds are calculated as a function of the rate of the various partial reactions of photosynthesis, at various external concentrations which span those likely to occur in vivo. It is shown how the net transport requirements of the various reactions necessitate different adjustments in the stromal concentrations of these compounds, away from the equilibrium values expected in the absence of metabolism. Under most circumstances, the high exchange capacity of the phosphate translocator relative to the transport requirements of CO(2) fixation limits the extent of these displacements, but conditions when the phosphate translocator is limiting photosynthesis are observed and discussed. The model provides a basis for a more quantitative understanding of the role of the phosphate translocator and the external concentrations of phosphate, 3-phosphoglycerate, and dihydroxyacetone phosphate in photosynthesis.


[Actual situations and problems of patients receiving home IVH--trial use of an assessment chart for outpatients].
In order to improve the quality of life (QOL) and continue nursing, we used an assessment chart to investigate the actual situations and problems of the patients receiving home intravenous hyperalimentation (IVH). From January, 1997 to June, 1999, we investigated 20 patients with home IVH. To 7 patients among them, we asked questions using Kurihara's assessment chart for QOL, plus our original questions concerning IVH. The mean age of the patients was 61 years old, and 19 of them had advanced cancers. Forty percent of the patients maintained the IVH all by themselves and 10% of the patients needed the support of their family. The remaining 50% of the patients left all to their family. There were 9 incidents of trouble during the maintenance of the IVH. Almost all patients from whom informed consent had been received were satisfied with the home IVH. On the contrary, all patients who had not given informed consent were not satisfied with the home IVH. According to the results of the assessment chart, even if the total points were low, the points for the IVH were high in the patients had given informed consent. The main reason for lower QOL was pain. The points for the families were lower than those for the patients. They sometimes complained of uneasiness and dissatisfaction with the support they received. We conclude that therapies to improve symptoms and mental state are necessary to satisfy the patients, and that it is important to support not only the patients but also their families.


Parallel Synthesis of bis-heterocyclic isoxazolylmethyl- and isoxazolinylmethylpyrazoles.
The solution-phase parallel synthesis of a 136-member library of isoxazol(in)e-CH(2)-pyrazoles is described. X-ray crystallographic structure determination verified the regioselectivities of the N-alkylation and nitrile oxide 1,3-dipolar cycloaddition steps. The construction of these pharmaceutically relevant heterocycles on solid support under microwave irradiation is also demonstrated. The resulting library of drug-like compounds has been added to the National Institutes of Health repository (approximately 10 mg of each with >or=90% purity) for pilot-scale biomedical studies with bioassay data available at the National Center for Biotechnology Information PubChem database. A subset of these compounds has been broadly screened by Dow AgroSciences for herbicidal, fungicidal, and insecticidal activity.


GTP-binding proteins in intracellular transport.
One of the most exciting recent discoveries in the area of intracellular protein transport is the finding that many organelles involved in exocytic and endocytic membrane traffic have one or more Ras-like GTP-binding proteins on their cytoplasmic face that are specific for each membranous compartment. These proteins are attractive candidates for regulators of transport vesicle formation and the accurate delivery of transport vesicles to their correct targets.


Identification and effects of maize silk volatiles on cultures of Aspergillus flavus.
Volatiles generated from corn silks of individual genotypes of maize were found to exhibit differences in biological activities when the volatiles were exposed to 5-day solid cultures of Aspergillus flavus. In inverted potato dextrose-agar Petri plate bioassays, it was found that volatiles emitted from silks of the different maize genotypes had a profound effect on the growth of the fungus and, consequently, aflatoxin production. To determine the underlying cause for this bioactivity, volatiles emitted from the maize silks were trapped on Tenax glass columns and were analyzed by GC-MS. Aflatoxin field-resistant maize genotypes exhibited a larger relative concentration of the antifungal aldehyde, furfural (2-furancarboxaldehyde), when compared to the relative concentrations of the field-susceptible varieties tested. In a closed-container 5-day study, it was observed that fresh 1- and 4-day-old corn silk samples of aflatoxin-resistant maize genotypes emitted higher concentrations of furfural compared to those from susceptible genotypes. This observation probably explains the reason for the bioactivity observed in the in vitro bioassays, and the presence of furfural appears to contribute to a defense mechanism for protecting the developing maize kernel from fungal attack.


Patterns of restenosis for the SFA: The second step on a long journey.
Restenosis patterns required better definitions Defining restenosis patterns may help compare technologies better Further research with consistent restenosis pattern definition will help us define the most value-added treatments.


[Impact of surgical treatment of female stress urinary incontinence on the quality of life of patients].
To evaluate the quality of life of patients with stress urinary incontinence (SUI) operated in the Department of Urology at the Complejo Hospitalario Universitario in Albacete (CHUA). Between November 2001 and December 2005, 126 patients with SUI have completed a questionnaire in our centre, before and after undergoing surgery with sling techniques. The questionnaire was the King's Health Questionnaire (KHQ), which is a specific instrument for the measurement of quality of life in patients with urinary incontinence. Mean patient's age was 57.09 years (DE: 9.57). Twelve women (9.5%) had history of previous urinary incontinence surgery. Mean urinary incontinence evolution time was 114.48 months, with a median of 96 months. 38 patients (30.2%) did not present cystocele, 61 (48.4%) presented grade III cystocele, 25 (19.8%) grade II, and 2 (1.6%) grade I. Before surgery, the scale with best score was Personal relationships, with a mean score of 26.8, whereas the scale with worst scores was Impact of urinary incontinence, with a mean score of 82.96. All operations performed consisted in various techniques of transvaginal slings, except one case (0.8%) in which the Kelly technique was performed. Impact of urinary incontinence was the scale with a greater number of patients improving after surgery; 82.9% of the patients (101 cases) gave a better score. The scales showing greater differences of the mean value comparing before/after surgery were impact of urinary incontinence, limitation on the daily life activity, and limitation on social activity. Personal relationships and General health were the two with the smallest improvements. Surgery demonstrated to improve the symptoms secondary to this disease, therefore, it results in an improvement of the quality of life that is evident in all scales of the questionnaire, mainly in the impact of urinary incontinence, limitations on physical activity, limitations on daily life, and limitation on social activity scales.


White matter tract clustering and correspondence in populations.
We present a novel method for finding white matter fiber correspondences and clusters across a population of brains. Our input is a collection of paths from tractography in every brain. Using spectral methods we embed each path as a vector in a high dimensional space. We create the embedding space so that it is common across all brains, consequently similar paths in all brains will map to points near each other in the space. By performing clustering in this space we are able to find matching fiber tract clusters in all brains. In addition, we automatically obtain correspondence of tractographic paths across brains: by selecting one or several paths of interest in one brain, the most similar paths in all brains are obtained as the nearest points in the high-dimensional space.


A rare case of bullhorn-injury associated traumatic hernia of anterior abdominal wall managed by laparoscopic sutured tissue-only repair.
Traumatic abdominal wall hernias (TAWHs) are relatively uncommon entities. Common mechanisms that predispose to such hernias include motor vehicle accidents, seat belt injuries, fall from height, handlebar injuries, and bullfighting. Bullhorn injury leading to TAWHs is an uncommon mechanism. We report here one such patient who was managed by laparoscopic transperitoneal anatomical repair of the defect using polypropylene suture. The patient recovered well without any complication and is being followed up. Such small defects can be managed laparoscopically and tissue-only repair using a nonabsorbable suture is a feasible option. Our case is the first reported case of bullhorn-injury associated traumatic hernia managed laparoscopically and first reported case of TAWH in an adult which was managed by laparoscopic sutured tissue-only repair.


[Psychosomatic approach to allergies].
Allergies are a physical manifestation which can be approached positively. Localising the allergy enables the link with the person's history to be identified and helps to give meaning to the symptoms. Kinesiology and Chinese medicine can complement the western approach to the illness.


Transcriptional organization of the Pseudomonas putida tol-oprL genes.
Proteins of the Tol system play a key role in the maintenance of outer membrane integrity and cell morphology in gram-negative bacteria. In Pseudomonas putida, the seven genes, orf1, tolQ, tolR, tolA, tolB, oprL, and orf2, which encode the proteins of this complex, are clustered in a 5.8-kb region of chromosomal DNA. Analysis of polar mutations, reverse transcriptase PCR assays, and transcriptional fusion constructs with a promoterless lacZ gene revealed that the genes are arranged in two operons: orf1 tolQ tolR tolA tolB and oprL orf2. We were also able to find a transcript that was initiated at the orf1 promoter and covered the two operons in a single mRNA. On the basis of the OprL protein level, we surmised that this transcript contributed only about 10 to 15% of the total OprL protein. Primer extension analysis identified the oprL orf2 operon promoter within the tolB gene, and the -10 and -35 regions exhibited some similarity to those of sigma(70)-recognized promoters. The transcription start point of orf1 was located 91 bp upstream of the orf1 start codon, and the -10/-35 region also exhibited sigma(70) -10/-35 recognition sequences. The expression from both promoters in rich and minimal media was constitutive and was very little influenced by the growth phase or iron-deficient conditions. In addition, analyses of the beta-galactosidase activities of different translational fusion constructs revealed that translation of tolA and orf2 genes was dependent on the translation of their corresponding upstream genes (tolR and oprL, respectively).


Mediastinal Lymphadenopathy, Class-Switched Auto-Antibodies and Myocardial Immune-Complexes During Heart Failure in Rodents and Humans.
Mediastinal lymphadenopathy and auto-antibodies are clinical phenomena during ischemic heart failure pointing to an autoimmune response against the heart. T and B cells have been convincingly demonstrated to be activated after myocardial infarction, a prerequisite for the generation of mature auto-antibodies. Yet, little is known about the immunoglobulin isotype repertoire thus pathological potential of anti-heart auto-antibodies during heart failure. We obtained human myocardial tissue from ischemic heart failure patients and induced experimental MI in rats. We found that anti-heart autoimmunity persists during heart failure. Rat mediastinal lymph nodes are enlarged and contain active secondary follicles with mature isotype-switched IgG2a B cells. Mature IgG2a auto-antibodies specific for cardiac antigens are present in rat heart failure serum, and IgG and complement C3 deposits are evident in heart failure tissue of both rats and human patients. Previously established myocardial inflammation, and the herein provided proof of B cell maturation in lymph nodes and myocardial deposition of mature auto-antibodies, provide all the hallmark signs of an established autoimmune response in chronic heart failure.


Leadership through interdisciplinary teams: a case study of an acute pain service.
Interdisciplinary teams are rapidly becoming the standard for the organization and delivery of acute care services. Increasingly, research is showing that an interdisciplinary approach has the potential to improve patient care. Implementing a team approach, however, has challenges because of the various perspectives that different disciplines bring. In this paper we present a case study of an Acute Pain Service to illustrate how an interdisciplinary team can work to improve pain management in hospitals. The development of the Acute Pain Service will be described along with a discussion of the challenges that were faced. Key lessons will be presented that may lend direction for the implementation of an Acute Pain Service or for any other interdisciplinary team.


North Spain (Burgos) wild mammals ectoparasites.
Twenty-seven species of arthropods were collected from 105 wild mammals, six wolves Canis lupus (Linnaeus, 1758) included. A total of 87 animals (82.8%) harboured some ectoparasites. Ticks were found in 60% of the samples, fleas in 51.4%, chewing-lice in 3.8%, and others (Mesostigmata and hippoboscids) in 3.8%. Moreover, 42.5% were single infestation and 57.5% mixed. Some of the species were new records for a host in spanish country such as Trichodectes canis (De Géer, 1778), Ixodes trianguliceps (Birula, 1895), Ceratophyllus (Monopsyllus) S. sciurorum (Schrank, 1803) and Paraceras melis melis (Walker, 1856) on several mammals. Two species were new records for Spain: Chaetopsylla matina (Jordan, 1925) and Archaeopsylla erinacei erinacei (Bouché, 1835).


Covid-19-associated fungal osteomyelitis of jaws and sinuses: An experience-driven management protocol.
Invasive fungal co-infections with COVID-19 are currently being reported at an alarming rate. Our study explores the importance of early identification of the disease, probable etiopathogenesis, clinical and radiological features and a treatment protocol for COVID-19 Associated Fungal Osteomyelitis of Jaws and Sinuses (CAFOJS). A one-year prospective study from June 2020 to May 2021 was conducted among CAFOJS diagnosed patients at a tertiary care center in South India. Demographic details, COVID-19 infection and treatment history, time taken for initiation of symptoms after COVID-19 diagnosis, medical history and clinical features were recorded. All patients were managed with a standard diagnostic and intervention protocol which included pre-operative and post-operative administration of Inj. Amphotericin B 50 mg (liposomal), early aggressive surgical debridement and tab. Posaconazole GR 300 mg OD for 90 days after discharge. Thirty-nine (78%) patients were diagnosed with CAFOJS out of 50 osteomyelitis patients. 35 patients (90%) were diabetic and 21 patients (54%) were known to receive steroids during the COVID-19 treatment. Sole existence of Mucorales spp. was seen in 30 patients (77%), Aspergillus fumigatus in 2 patients (5%), Curvularia spp. in 2 patients (5%). Concomitant existence of Mucorales and Aspergillus fumigatus was reported in two patients (5%) and Candida albicans in three patients (8%). Patients underwent treatment with standard protocol and no recurrence noted. CAFOJS is a clinical entity with aggressive presentation and warrants early diagnosis and treatment. Invasive fungal infections of head and neck region cause necrosis of bones affected by it, especially maxilla. Early diagnosis and treatment are advocated in such infections due to its aggressive clinical presentation compared to similar infections before COVID-19 pandemic.


Tophaceous pseudogout of the temporomandibular joint extending into the cranium: a case report with literature review.
Pseudogout is a disease characterized by calcium pyrophosphate crystal deposition. Involvement of the temporomandibular joint (TMJ) is rare. We herein report a case of tophaceous pseudogout of the TMJ with cranial extension. An 83-year-old woman was referred to our institution for treatment of right TMJ pain. The patient's medical and family histories were unremarkable. Magnetic resonance imaging showed a mass of about 35 mm in diameter compressing the bottom of the right temporal lobe of the brain. Based on a clinical diagnosis of a right TMJ tumour, biopsy was performed under general anaesthesia. The histopathological diagnosis was pseudogout. Considering the risk of surgically induced brain damage, the patient's advanced age and her relatively good quality of life, the treatment plan simply involved the observation of the lesion. Fourteen months after biopsy, the patient's activities of daily living remained unchanged and she had no TMJ pain.


Strong reciprocal interaction between polarization and surface stoichiometry in oxide ferroelectrics.
We present a systematic evaluation of the effects of polarization switchability on surface structure and stoichiometry in BaTiO3 and PbTiO3 ferroelectric oxides. We show that charge passivation, mostly by ionic surface reconstructions, is the driving force for the stability of the surfaces, which suggests that varying the substrate polarization offers a new mechanism for controlling surface reconstructions in polar systems and inducing highly nonstoichiometric structures. Conversely, for thin-films the chemical environment can drive polarization switching via induced compositional changes on the surface. We find that the value of the oxygen partial pressure for the positive-to-negative polar transition is in good agreement with the recent experimental value for thin-film PbTiO3. For BaTiO3, we show that it is harder for oxygen control to drive polar transition because it is more difficult to reduce. This study opens up the possibility of real-time control of structure and composition of oxide surfaces.


Hydroxybenzaldoximes Are D-GAP-Competitive Inhibitors of E. coli 1-Deoxy-D-Xylulose-5-Phosphate Synthase.
1-Deoxy-D-xylulose 5-phosphate (DXP) synthase is the first enzyme in the methylerythritol phosphate pathway to essential isoprenoids in pathogenic bacteria and apicomplexan parasites. In bacterial pathogens, DXP lies at a metabolic branch point, serving also as a precursor in the biosynthesis of vitamins B1 and B6, which are critical for central metabolism. In an effort to identify new bisubstrate analogue inhibitors that exploit the large active site and distinct mechanism of DXP synthase, a library of aryl mixed oximes was prepared and evaluated. Trihydroxybenzaldoximes emerged as reversible, low-micromolar inhibitors, competitive against D-glyceraldehyde 3-phosphate (D-GAP) and either uncompetitive or noncompetitive against pyruvate. Hydroxybenzaldoximes are the first class of D-GAP-competitive DXP synthase inhibitors, offering new tools for mechanistic studies of DXP synthase and a new direction for the development of antimicrobial agents targeting isoprenoid biosynthesis.


Biosynthesis of marine natural products: isolation and characterization of a myrcene synthase from cultured tissues of the marine red alga Ochtodes secundiramea.
The acyclic monoterpene myrcene is the likely progenitor of the unusual cytotoxic halogenated monoterpenes that are found in marine algae and that function as feeding deterrents to herbivores. Myrcene synthase was isolated from suspension cultures of the marine red alga Ochtodes secundiramea, representing the first enzyme of this type from a marine organism. The algal myrcene synthase produces exclusively myrcene from the natural substrate geranyl diphosphate (GDP), utilizes Mg(+2) as the required divalent metal ion cofactor, has a molecular mass of about 69 kDa, and exhibits a pH optimum near 7.2. These features are similar to those of monoterpene synthases from terrestrial organisms. When incubated with neryl diphosphate (the cis-isomer of GDP), the O. secundiramea myrcene synthase produces the cyclic monoterpene limonene, whereas incubation with (+/-)linalyl diphosphate (the tertiary allylic isomer of geranyl diphosphate) yields both acyclic and cyclic monoterpenes. These results suggest that the enzyme is incapable of isomerizing geranyl diphosphate to linalyl diphosphate, a feature common to all monoterpene cyclases from terrestrial sources. The limited catalytic capability of the myrcene synthase may reflect the ancient evolutionary origin of the producing organism. The ability to assay this enzyme in cultured algae, grown under strictly defined conditions, provides an unparalleled opportunity to delineate factors eliciting the biosynthesis of this class of secondary metabolites, to investigate the metabolic pathway leading to the halogenated monoterpenes, and to determine their role in the chemical ecology of marine algae.


Computational and Further Experimental Explorations of the Competing Cascades Following Claisen Rearrangements of Aryl Propargyl Ethers: Substituent Effects on Reactivity and Regioselectivity.
We report a computational investigation of two reaction cascades occurring following the Claisen rearrangements of aryl propargyl ethers to the alternate ortho positions in unsymmetrical reactants. Our computations explain how substituents influence reactivity and regioselectivity. Rearrangement to the substituted ortho carbon leads to a tricyclo[220.127.116.11]octane core, while rearrangement to an unsubstituted ortho carbon leads to a benzopyran. Density functional theory with ωB97X-D indicates that these reactions involve rate-determining Claisen rearrangements followed by subsequent reaction cascades of the Claisen rearrangement products depending on the presence or absence of a substituent at the ortho carbon.


Establishing the Minimal Clinically Important Difference, Patient Acceptable Symptomatic State, and Substantial Clinical Benefit of the PROMIS Upper Extremity Questionnaire After Rotator Cuff Repair.
The Patient-Reported Outcome Measurement Information System Upper Extremity (PROMIS UE) questionnaire has been validated as an effective and efficient outcome measure after rotator cuff repair (RCR). However, definitions of clinically significant outcomes used in interpreting this outcome measure have yet to be defined. To define clinically significant outcomes of the PROMIS UE questionnaire in patients undergoing arthroscopic RCR. Cohort study (diagnosis); Level of evidence, 3. We reviewed charts of consecutive patients undergoing RCR in our institution between 2017 and 2018 and included patients who were administered the PROMIS UE before surgery and 12 months after surgery. At 12 months postoperatively, patients were asked domain-specific anchor questions regarding their function and satisfaction after surgery, which were then used to determine the minimal clinically important difference (MCID), Patient Acceptable Symptomatic State (PASS), and substantial clinical benefit (SCB) using receiver operating characteristic and area under the curve (AUC) analysis. Univariate and multivariate logistic regression analysis was utilized to identify patient factors associated with clinically significant outcomes. A total of 105 patients with RCR and minimum 12-month postoperative PROMIS UE were included in the analysis. The defined clinically significant outcomes were 4.87 for the MCID using a distribution-based method, 7.95 for the SCB (sensitivity, 0.708; specificity, 0.833; AUC, 0.760), and 39.00 for the PASS (sensitivity, 0.789; specificity, 0.720; AUC, 0.815). Among respondents, 79.0%, 62.9%, and 64.8% achieved the MCID, SCB, and PASS score thresholds, respectively. Workers' compensation was negatively associated with achievement of the PASS. Lower preoperative PROMIS UE scores were associated with obtaining the MCID (odds ratio [OR], 0.871; P = .001) and the SCB (OR, 0.900; P = .040), whereas higher preoperative scores were predictive of achieving the PASS (OR, 1.111; P = .020). This study defines the clinically significant outcomes for the PROMIS UE after RCR, of which the majority of patients achieved the MCID, PASS, and SCB at 12 months after surgery. These thresholds should be considered in future study design and interpretation of PROMIS UE in patients with RCR.


Germ Cell Tumors in Adolescents and Young Adults.
Germ cell tumors (GCTs) represent a group of biologically complex malignancies that affect patients at different sites within the body and at different ages. The varying nature of these tumors reflects their cell of origin which is the primordial germ cell, which normally gives rise to ovarian and testicular egg and sperm producing cells. These cells retain an ability to give rise to all types of human tissues, and this is illustrated by the different kinds of GCTs that occur. In adolescent and young adult (AYA) patients, GCTs predominantly present as testicular, ovarian or mediastinal primary GCTs, and represent some of the most complex therapeutic challenges within any AYA practice. The varying types of GCTs, defined by primary site and/or age at presentation, can look very similar microscopically. However, there is growing evidence that they may have different molecular characteristics, different biology and different requirements for curative treatments. Whilst in adult testicular GCTs there is evidence for an environmental cause during fetal development and a genetic component, these causative factors are much less well understood in other GCTs. GCTs are some of the most curable cancers in adults, but some patients exhibit resistance to standard treatments. Because of this, today's clinical research is directed at understanding how to best utilize toxic therapies and promote healthy survivorship. This chapter explores the biology, behavior and treatment of GCTs and discusses how the AYA group of GCTs may hold some of the keys to understanding fundamental unanswered questions of biological variance and curability in GCTs.


Darwin was right: where now for experimental evolution?
Over the last two decades interest in direct realisation of evolutionary process and the possibilities presented by real time evolution experiments with microbes have escalated. Long-term selection experiments with bacteria have made increasingly transparent the process of evolution by natural selection. In this short article we consider what next for the field and do so by highlighting two areas of interest: the genotype-to-phenotype map and the constraints it imposes on evolution, and studies on major evolutionary transitions and in particular the importance of selection working over more than one timescale. The latter we discuss in light of new technologies that allow imposition of Darwinian properties on populations and communities and how this allows exploration of new avenues of research. We conclude by commenting on microbial communities and the operation of evolutionary processes that are likely intrinsic-and specific-to communities.


Comparison of early and delayed scintigraphy with 99mTc-apcitide and correlation with contrast-enhanced venography in detection of acute deep vein thrombosis.
Preliminary studies with 99mTc-apcitide (99mTc-P280), a synthetic peptide that binds to glycoprotein IIb/IIIa receptors expressed on activated platelets, have shown promising results in the detection of acute deep vein thrombosis (ADVT). The purpose of this study was to compare the diagnostic value of early and delayed imaging with 99mTc-apcitide in patients with suspected ADVT, using contrast-enhanced venography as the gold standard. Thirty-nine patients (17 women, 22 men; mean age 59 y) with signs or symptoms suggestive of ADVT (within 10 d of onset) and scheduled for contrast-enhanced venography were prospectively studied. The patients were injected with approximately 740 MBq (20 mCi) 99mTc-apcitide within 36 h of contrast-enhanced venography. Both anterior and posterior planar images (8-10 min/view) of the lower extremities using a dual-head gamma camera were obtained at 10, 60 and 120 min after the injection of 99mTc-apcitide. The three sets of images initially were interpreted randomly and separately by three experienced observers unaware of the clinical history, the site of ADVT and results of contrast-enhanced venography. All images from the three sets for a given patient were then analyzed together during a second session. Conventional contrast-enhanced venography was performed on 31 patients before 99mTc-apcitide scintigraphy and in the remaining 8 patients after 99mTc-apcitide scintigraphy. 99mTc-apcitide findings were considered positive forADVT when a focus of increased uptake was found to correspond to the location of a deep vein. Disagreements were resolved by consensus. Twenty-two patients had ADVT observed on contrast-enhanced venography, whereas 17 had normal findings. Six cases of ADVT were infrapopliteal. One patient did not complete the third set of images with 99mTc-apcitide. The sensitivity of 99mTc-apcitide in detecting ADVT was 63.6% (14/22), 68.2% (15/22), 76.2% (16/21) and 86.4% (19/22) for images obtained at 10, 60 and 120 min and for the three sets analyzed together, respectively. The specificity was 82.4% (14/17), 76.5% (13/17), 88.2% (15/17) and 88.2% (15/17) for images obtained at 10, 60 and 120 min and for the three sets of images together, respectively. Although the set of 99mTc-apcitide images obtained 120 min after injection showed good overall diagnostic accuracy, the combination of at least two sets of images provided the highest accuracy in detecting ADVT.


Effect of the carboxylic ionophore monensin on histamine release from rat peritoneal mast cells.
The effect of the monovalent carboxylic ionophore monensin, which mediates a one-for-one exchange of intracellular H+ for extracellular Na+, was investigated in purified rat peritoneal mast cells. Monensin inhibited histamine secretion induced by compound 48/80, adriamycin and the calcium ionophore A23187; the inhibitory effect was maximal when the compound was added at least 10 min before the secretagogues. Washing of cells before addition of the secretagogues did not abolish the inhibitory effect of monensin. On the contrary the carboxylic ionophore was completely ineffective in preventing concanavalin A-induced histamine release. When rat peritoneal mast cells were incubated in the presence of monensin for longer period (up to 5 hours), the substance induced a slow, progressive and dose dependent histamine release, which, at least for lower doses was noncytotoxic. The secretory effect of monensin was still present if the ionophore was washed away after 10 min of incubation, and the incubation continued in drug-free medium. Monensin stimulated histamine secretion was strictly dependent on extracellular Na+ concentrations, and independent on extracellular Ca++.


Development and Validation of the Occupational Therapy Engagement Scale for Patients with Stroke.
Almost all interventions in occupational therapy require the active engagement of the patients. However, no scale has been specifically designed for assessing engagement in occupational therapy. The purposes of this study were to develop the occupational therapy engagement scale (OTES) and to examine its unidimensionality, reliability, and predictive validity. The OTES was developed through the review of similar scales, eight experts' opinions, cognitive interviews, and pilot testing. The unidimensionality was verified with Rasch model fitting and principal component analysis. The Rasch reliability was also estimated. Pearson's correlation coefficient (r) was used to validate the predictive validity by examining the association between the Rasch scores of the OTES and patients' performance of activities of daily living (ADL). A total of 253 patients with stroke were rated by 22 therapists using the OTES. The mean age of the patients was 62.3 ± 13.2 years old, and 65.2% of the patients were male. The infit and outfit MNSQ of the 12 items of the OTES ranged from 0.62 to 1.34. The unexplained variance of the first dimension of the principal component analysis was 4.0%. The mean person reliability of the OTES was 0.88. Pearson's r between the OTES and patients' ADL performance was 0.37. The results of Rasch analysis supported that the items of the OTES were unidimensional. The OTES had sufficient person reliability and predictive validity in patients with stoke.


DNA cleavage by oxymyoglobin and cysteine-introduced metmyoglobin.
Double stranded DNA was cleaved oxidatively by incubation with oxygenated myoglobin, and Lys96Cys sperm whale myoglobin in its stable ferric form functioned as an artificial nuclease under air by formation of an oxygenated species, owing to electron transfer from the SH group of the introduced cysteine to the heme.


In vitro characterization of tomato fruit softening : the use of enzymically active cell walls.
Cell wall isolated from pericarp of normal tomato (Lycopersicon esculentum Mill. cv ;Rutgers') fruit released pectic polymers in a reaction apparently mediated by wall-bound polygalacturonase that appears with the onset of ripening. Release was negligible in wall preparations from normal green and the ripening mutant rin fruit. Pectin solubilization was most extensive at pH 2.5 with a less significant peak at 5.5. Brief exposure to low (1.5) or high (7.5) pH resulted in reduction of autolytic activity, which was also inhibited by high temperature, Ca(2+), and treatments employed to dissociate protein from cell wall. Uronic acid solubilization was significantly enhanced by 150 millimolar NaCl and by increasing temperature within the physiological range. These data indicate that the release of polyuronide from isolated cell walls is enzymic and may provide a convenient and reliable system for the study of softening metabolism.


Some gastrointestinal nematodes and ixodid ticks shared by several wildlife species in the Kruger National Park, South Africa.
Parasite surveys were conducted for 1–2 years in the Kruger National Park (KNP), South Africa on blue wildebeest, impalas, greater kudus, common warthogs and scrub hares. The host associations of some of the gastrointestinal nematode species infecting ≥60% of at least one of the five host species, were determined. These were Agriostomum gorgonis, Cooperia acutispiculum, Cooperia connochaeti, Cooperia hungi, Cooperia neitzi, Cooperioides hamiltoni, Gaigeria pachyscelis, Haemonchus bedfordi, Haemonchus krugeri, Haemonchus vegliai, Impalaia tuberculata, Longistrongylus sabie, Strongyloides papillosus, Trichostrongylus deflexus and Trichostrongylus thomasi. Although the prevalence of Trichostrongylus falculatus did not exceed 50% in any host species, it was present in all five hosts. Nematodes in the KNP range from those exhibiting strict host associations to generalists. Nematode-host associations may be determined by host feeding patterns and habitat use. Eight ixodid tick species were commonly collected from the same animals and in 2–3 year long surveys from plains zebras and helmeted guinea fowls: Amblyomma hebraeum, Amblyomma marmoreum, Hyalomma truncatum, Rhipicephalus appendiculatus, Rhipicephalus decoloratus, Rhipicephalus evertsi evertsi, Rhipicephalus simus and Rhipicephalus zambeziensis. Host specificity was less pronounced in ixodid tick species than in nematodes and the immature stages of five tick species infested all host species examined.


Maxillary lesion presenting as a first sign of multiple myeloma: case report.
Plasma cell neoplasia is a lymphoid neoplastic proliferation of B cells. This denomination encloses multiple myeloma (MM), solitary bone plasmacytoma and extramedullary plasmacytoma. MM consists of a clonal proliferation of plasma cells based in the bone marrow, with various degrees of differentiation. Neoplastic cells usually produce great amounts of monoclonal light or heavy chains of immunoglobulin that can be detected in serum or urine. The disease is more frequently in men and the average age at diagnosis is about 60 years. The diagnosis is established by blood and urine exams and medullary biopsy. Patients may present renal failure, bone pain, fatigue, recurrent infections and nervous system dysfunction. Oral manifestations may be the first sign of MM, highlighting the importance of the dentist in the early diagnosis of the disease. Treatment involves mainly irradiation and chemotherapy and the prognosis is generally poor. This paper reports a case of a 65 years old black female who had a complaint of a painful mass in the maxilla that prompted a MM diagnosis.


[Size of acoustic neurinomas assessed by CT and magnetic resonance scanning].
Some acoustic neuromas do not grow or grow very slowly. It is therefore of value to compare the results of measuring the size of acoustic neuromas by either CT or Magnetic Resonance Imaging (MRI) scanning with a view to being able to observe the growth rate of these tumours. Fifteen patients with acoustic neuromas had both CT- and MRI-scans performed. Two trained radiologists evaluated the size of the tumours in a blinded fashion. There was a significant difference between one observer's calculations from the CT- and the MRI-scans, and also a significant difference between the two observers' calculations from the CT-scans. No difference in calculating tumour size was found between the two observers' calculations from the MRI-scans. It is concluded that the size of acoustic neuromas i evaluated more equally by two observers using MRI-scans than when using CT-scans. By the use of repeated MRI-scanning it is possible to keep patients with acoustic nouromas under observation and avoid operation in those patients where the tumour does not grow.


Fluctuating asymmetry as an indicator of fitness: can we bridge the gap between studies?
There is growing evidence from both experimental and non-experimental studies that fluctuating asymmetry does not consistently index stress or fitness. The widely held--yet poorly substantiated--belief that fluctuating asymmetry can act as a universal measure of developmental stability and predictor of stress-mediated changes in fitness, therefore staggers. Yet attempts to understand why the reported relationships between fluctuating asymmetry, stress and fitness are so heterogeneous--i.e. whether the associations are truly weak or non-existent or whether they become confounded during different stages of the analytical pathways remain surprisingly scarce. Hence, we attempt to disentangle these causes, by reviewing the various statistical and conceptual factors that are suspected to confound potential relationships between fluctuating asymmetry, stress and fitness. Two main categories of factors are discerned: those associated with the estimation of developmental stability through fluctuating asymmetry and those associated with the effects of genotype and environment on developmental stability. Next, we describe a series of statistical tools that have recently been developed to help reduce this noise. We argue that the current lack of a theoretical framework that predicts if and when relationships with developmental stability can be expected, urges for further theoretical and empirical research, such as on the genetic architecture of developmental stability in stressed populations. If the underlying developmental mechanisms are better understood, statistical patterns of asymmetry variation may become a biologically meaningful tool.


[Idiopathic ventricular fibrillation].
In 1 to 8% of survivors of syncopal ventricular fibrillation, it is impossible to identify a structural cardiac abnormality. Idiopathic ventricular fibrillation, a diagnosis of exclusion, is a term which includes a variety of diseases. This article describes several well defined electro-clinical entities: Brugada's syndrome, torsades de pointes with a short coupling interval, catecholinergic polymorphic ventricular tachycardia and the acquired long QT syndrome. In the majority of these cases, despite the fact that their physiopathology is not fully understood, the management is clear-cut. However, in a large number of patients, the choice between pharmacological treatment and the implantation of an automatic defibrillator remains difficult. Molecular biological studies and strict clinical investigation, standardised with the help of networks, should provide a rational approach to the treatment of idiopathic ventricular fibrillation.


Interferon-alpha mediates restriction of human immunodeficiency virus type-1 replication in primary human macrophages at an early stage of replication.
Type I interferons (IFNα and β) are induced directly in response to viral infection, resulting in an antiviral state for the cell. In vitro studies have shown that IFNα is a potent inhibitor of viral replication; however, its role in HIV-1 infection is incompletely understood. In this study we describe the ability of IFNα to restrict HIV-1 infection in primary human macrophages in contrast to peripheral blood mononuclear cells and monocyte-derived dendritic cells. Inhibition to HIV-1 replication in cells pretreated with IFNα occurred at an early stage in the virus life cycle. Late viral events such as budding and subsequent rounds of infection were not affected by IFNα treatment. Analysis of early and late HIV-1 reverse transcripts and integrated proviral DNA confirmed an early post entry role for IFNα. First strand cDNA synthesis was slightly reduced but late and integrated products were severely depleted, suggesting that initiation or the nucleic acid intermediates of reverse transcription are targeted. The depletion of integrated provirus is disproportionally greater than that of viral cDNA synthesis suggesting the possibility of a least an additional later target. A role for either cellular protein APOBEC3G or tetherin in this IFNα mediated restriction has been excluded. Vpu, previously shown by others to rescue a viral budding restriction by tetherin, could not overcome this IFNα induced effect. Determining both the viral determinants and cellular proteins involved may lead to novel therapeutic approaches. Our results add to the understanding of HIV-1 restriction by IFNα.


Classification and comparison of niche services for developing strategy of medical tourism in Asian countries.
Medical tourism is a new trend in medical service. It is booming not only in Asian countries but also in European and South American countries. Worldwide competition of medical service is expected in the future, and niche service will be a "trademark" for the promotion of global medicine. Niche service also functions for market segmentation. Niche services are usually surgical procedures. A study was carried out to compare different strategies for developing medical tourism in Asian countries. The role of a niche service is evaluated in the initiation and further development of medical tourism for individual countries. From this study, a general classification was proposed in terms of treatment procedures. It can be used as a useful guideline for additional studies in medical tourism. Niche service plays the following roles in the development of medical tourism: (1) It attracts attention in the mass media and helps in subsequent promotion of business, (2) it exerts pressure on the hospital, which must improve the quality of health care provided in treating foreign patients, especially the niche services, and (3) it is a tool for setting up the business model. E-Da Hospital is an example for developing medical tourism in Taiwan. A side effect is that niche service brings additional foreign patients, which will contribute to the benefit of the hospital, but this leaves less room for treating domestic patients. A niche service is a means of introduction for entry into the market of medical tourism. How to create a successful story is important for the development of a niche service. When a good reputation has been established, the information provided on the Internet can last for a long time and can spread internationally to form a distinguished mark for further development. Niche services can be classified into 3 categories: (1) Low-risk procedures with large price differences and long stay after retirement; (2) high-risk procedures with less of a price difference, and (3) banned procedures that are not allowed legally in home countries of foreign patients, such as stem cell therapy. In establishing a niche service, a high-quality, nonmedical segment should be integrated as well.


[A case of amyopathic dermatomyositis with systemic sclerosis sine scleroderma presenting abnormal vermiculation].
A 24-year-old Japanese woman was admitted to our hospital in January 2000 with daily diarrhea, abdominal distention, and abdominal pain. Raynaud's phenomenon with erythroderma desquamativum eruptions had been found in 1992. In 1999, small intestinal transillumination showed dilation of the second and third portion of the duodenum. She was diagnosed as amyopathic dermatomyositis because of Gottron's sign despite not having symptoms of myositis, normal serum CPK levels and no histological abnormality by muscle biopsy. In addition, the patient was diagnosed as systemic sclerosis sine scleroderma because Raynaud's phenomenon, leukoma and gastrointestinal dilation were present. Also, antinuclear antibody and anti centromere antibody were positive and anti Scl-70 antibody was dull-positive, despite the absence of scleroderma, extreme edema, and bone resorption. Careful, long term observation will be required because of the splanchnopathy in youth and the complications of systemic sclerosis.


Impact of ultrasound application on oxidative desulphurization of diesel fuel and on treatment of resulting wastewater.
The ultrasound-assisted oxidative desulphurization (UAOD) process of diesel fuel has gained growing attention due to the strict regulation of sulphur content in the fuel. The goal of the present study was to investigate the impact of ultrasound (US) application for oxidative desulphurization (ODS) of hydrocarbon fuels and for the subsequent treatment of produced wastewater, since sonochemical processes are a new and interesting area of research with wide application in the field of environmental engineering. For that purpose, the model diesel fuel with initial sulphur concentration of 1220-3976 mg l(-1) was used for ODS and UAOD tests, and hydrogen peroxide/acetic acid was applied as the oxidant/catalyst system, respectively. The comparison of the process performance revealed that US significantly reduced the oxidation reaction time. The conversions of dibenzothiophene during 30 min of ODS and UAOD tests were 36% and 87%, respectively. Moreover, subsequent extraction with acetonitrile resulted in the final sulphur removal of 96.5%. The obtained results clearly indicated that UAOD process is beneficial for effective sulphur removal from the model diesel fuel. Furthermore, subsequent experiments included the application of the sono-Fenton process for resulting wastewater treatment. Monitoring of dibenzothiophene sulphone concentration and total organic carbon during the sono-Fenton treatment of wastewater revealed the decrease of 70-75% and 53-66%, respectively. The hypothesis on the possibility of degradation of dibenzothiophene sulphone by •OH radicals was confirmed by observed generation of benzoic acid and aliphatic carboxylic acids during experiments. Accordingly, the wastewater was purified to a satisfactory degree, enabling the reuse of treated water.


Changes in circulating parasite antigen levels after treatment of bancroftian filariasis with diethylcarbamazine and ivermectin.
This study assessed changes in circulating parasite antigen levels after diethylcarbamazine (DEC) and ivermectin treatment of bancroftian filariasis to determine effects of these drugs on adult Wuchereria bancrofti in vivo. Thirty adult Haitians with microfilaremia were treated with 1 mg of ivermectin to reduce counts of microfilariae. Later, subjects were treated with either one or two 200 micrograms/kg doses of ivermectin or with 12 daily 6 mg/kg doses of DEC. Macrofilaricidal activity of these drugs was indirectly monitored by measuring circulating W. bancrofti antigen by EIA. Antigen levels fell by 75% after DEC and by 34% after ivermectin. These results suggest that low-dose ivermectin treatment followed by a standard course of DEC is a more effective macrofilaricidal regimen for W. bancrofti than either of the multidose ivermectin regimens used in this study.


The value of cavernous body biopsy in evaluating of impotent men.
Rapid advances in the basic understanding of the anatomy, physiology and pharmacology of penile erection have drastically changed the clinical approach to patients with erectile dysfunction. To evaluate the value of microscopic architecture of the corpora cavernosa, we examined cavernous body biopsies taken during penile prosthesis implants. We studied on 12 impotent patients 25 to 67 years old who underwent implantation of a penile prosthesis. The biopsy was stained with H&E (Hematoxylin and Eosin) for general architecture, Masson Trichrome for collagen distribution and EVG for elastic fibers. Except 3 cases no pathological changes were determined at H&E staining. At collagen staining, roughly increased collagen distribution was determined in all cases. There were no appreciable differences in distribution of elastic fibers. In conclusion our data demonstrate that cavernous body biopsy is of limited value to determine etiologic factors in patients with erectile dysfunction.


Surgical outcomes according to distance between preplaced suture and muscle insertion in lateral rectus recession.
To compare surgical outcomes according to the distance between the preplaced suture and the muscle insertion in lateral rectus (LR) recession for exotropia. We retrospectively reviewed 64 patients who had undergone unilateral LR recession by one right-handed surgeon and divided the patients into 2 groups: right LR recession (R group, 26 patients) and left LR recession (L group, 38 patients). In the R group, the preplaced suture was behind the hook, far from the insertion; in the L group, the suture was in front of the hook, near the insertion. The main outcome measures were postoperative alignment and surgical success rate and the secondary outcome measure was effect/dose ratio. Surgical success was defined as an alignment between 10 prism diopters (PD) of exodeviation and 5 PD of esodeviation both at distance and at near. The effect/dose ratio was defined as the corrected angle of deviation at postoperative 6 months divided by the amount of LR recession. The mean angle of deviation at distance showed a significant difference between the groups at postoperative 3 months (p = 0.022), but not at final follow-up (p = 0.163). There was no difference between the groups in the mean angle of deviation at near postoperatively. Surgical success was achieved in 73.1% of the R group and 71.1% of the L group at final follow-up, which was not significant (p = 0.860). The distance between the preplaced suture and the muscle insertion in LR recession did not affect the surgical success rate or the postoperative alignment at final follow-up.


Short to Mid-Term Term Surgical Outcome Study with Posterior Only Approach on Tuberculous Spondylodiscitis in an Elderly Population.
Retrospective study. To study short to mid-term outcome of surgically managed elderly patients of tuberculous spondylodiscitis with posterior only approach in terms of decision making and challenges in treatment, choice of implants and outcomes. Tuberculous spondylodiscitis in the elderly is increasing due to longer survival rates. It presents with varied clinical manifestations needing surgical management. Management in tuberculous spondylodiscitis has been scarcely reported in the elderly, with a paucity of data on the choice of implants and approach. Sixteen patients (five males, 11 females) older than 70-years-of-age culture and/or histopathology proven tuberculous spondylodiscitis were included in the study. All patients were operated using a single posterior approach. Pedicle screw with rods (PS/rods) or spinal loop with sublaminar wires (SL/SLW) were used for fixation. Clinical and surgical details were recorded. Sagittal correction achieved postoperatively and loss of correction at follow-up were noted. The mean age was 73.6 years (range, 70 to 80 years). The mean follow up was 44.5 months (range, 24 to 84 months). The mean immediate postoperative correction of sagittal deformity was 11.3 degrees; this correction was lost by a mean of 3.1 degrees at last follow-up. All 10 patients with deficit showed neurological recovery and all but one of the seven non-walkers were capable of independent ambulation at follow-up. Patients with SL/SLW and PS/rods had similar radiological outcome at final follow up. Operative management gives satisfactory results in elderly patients with tuberculous spondylodiscitis. The posterior approach provides adequate exposure for decompression and rigid fixation, providing satisfactory clinical and radiological outcomes. SSL/SLW and pedicle screw rod construct both give similar radiological results if used appropriately in patients.


Use of electronic nicotine delivery systems by pregnant women II: Hair biomarkers for exposures to nicotine and tobacco-specific nitrosamines.
Public awareness of electronic nicotine delivery systems (ENDS) has increased over time, and the perception that ENDS offer a safer alternative to cigarettes may lead some pregnant women to use them to reduce cigarette smoking during pregnancy. No previous studies have used metabolite levels in hair to measure nicotine exposure for ENDS users during pregnancy. We aimed to measure and compare levels of nicotine, cotinine, and tobacco-specific nitrosamines (TSNAs) in hair samples from pregnant women who were current ENDS users, current smokers, and current non-smokers. We also aimed to estimate the association between ENDS use/smoking and smallness for gestational age (SGA). We used hair specimens from pregnant women who were dual users (ENDS and cigarettes), smokers, and non-smokers from a prospective cohort study to estimate exposure to nicotine, cotinine, and TSNAs. The exposure biomarkers and self-reports of smoking and ENDS use were used in log-binomial regression models to estimate risk ratios (RRs) for SGA among offspring. Nicotine concentrations for pregnant dual users were not significantly different from those for smokers (11.0 and 10.6 ng/mg hair, respectively; p=0.58). Similarly, levels of cotinine, and TSNAs for pregnant dual users were not lower than those for smokers. The RR for SGA was similar for dual users and smokers relative to nonsmokers, (RR=3.5, 95% CI: 0.8-14.8) and (RR=3.3, 95% CI: 0.9-11.6), respectively. Using self-reports confirmed by hair nicotine, the RR values for dual ENDS users and smokers were 8.3 (95% CI: 1.0-69.1) and 7.3 (95% CI:1.0-59.0), respectively. We did not observe lower levels of nicotine, cotinine, and TSNAs for current dual users compared to smokers during pregnancy. The risk of SGA for offspring of pregnant dual users was similar to that for offspring of pregnant smokers. Future studies are needed to further estimate the magnitude of the association between ENDS use and smallness for gestational age.


The use of quantile regression to forecast higher than expected respiratory deaths in a daily time series: a study of New York City data 1987-2000.
Forecasting higher than expected numbers of health events provides potentially valuable insights in its own right, and may contribute to health services management and syndromic surveillance. This study investigates the use of quantile regression to predict higher than expected respiratory deaths. Data taken from 70,830 deaths occurring in New York were used. Temporal, weather and air quality measures were fitted using quantile regression at the 90th-percentile with half the data (in-sample). Four QR models were fitted: an unconditional model predicting the 90th-percentile of deaths (Model 1), a seasonal/temporal (Model 2), a seasonal, temporal plus lags of weather and air quality (Model 3), and a seasonal, temporal model with 7-day moving averages of weather and air quality. Models were cross-validated with the out of sample data. Performance was measured as proportionate reduction in weighted sum of absolute deviations by a conditional, over unconditional models; i.e., the coefficient of determination (R1). The coefficient of determination showed an improvement over the unconditional model between 0.16 and 0.19. The greatest improvement in predictive and forecasting accuracy of daily mortality was associated with the inclusion of seasonal and temporal predictors (Model 2). No gains were made in the predictive models with the addition of weather and air quality predictors (Models 3 and 4). However, forecasting models that included weather and air quality predictors performed slightly better than the seasonal and temporal model alone (i.e., Model 3 > Model 4 > Model 2) This study provided a new approach to predict higher than expected numbers of respiratory related-deaths. The approach, while promising, has limitations and should be treated at this stage as a proof of concept.


Functional Connectivity of the Hippocampus in Early- and vs. Late-Onset Alzheimer's Disease.
Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) have different clinical and neuroimaging characteristics, but memory decline is usually present in both types. However, there have been few functional studies focused on the hippocampus in Alzheimer's disease. We therefore investigated the functional connectivity between the hippocampus and other brain regions using resting-state fMRI and compared the findings between EOAD and LOAD. We recruited 13 patients with EOAD and 19 patients with LOAD at the early disease stage. Twenty-one young controls and ten old controls were also recruited. Each participant completed a standardized neuropsychological battery of tests and underwent T1-weighted structural MRI. fMRI data were acquired during the resting state using 3-T MRI. The functional connectivity to the hippocampus was calculated based on automated anatomical labeling templates. The functional connectivity from the hippocampus to other brain regions differed between patients with EOAD and LOAD. The LOAD patients showed decreased hippocampal connectivity to cortical regions, such as to the middle temporal cortex, orbitofrontal cortex, postcentral cortex, supramarginal cortex, and rolandic operculum. In contrast, EOAD patients showed smaller functional changes of the cortical regions connected to the hippocampus, such as the middle frontal cortex. EOAD and LOAD patients exhibited different hippocampal connectivity. The memory decline in EOAD may be due to brain areas other than the hippocampus.


The challenge of developmental therapeutics for adrenocortical carcinoma.
Adrenocortical carcinoma (ACC) is a rare disease with an estimated incidence of only 0.7 new cases per million per year. Approximately 30-70% of the patients present with advanced disease with very poor prognosis and without effective therapeutic options. In the recent years, unprecedented progresses in cancer biology and genomics have fostered the development of numerous targeted therapies for various malignancies. Immunotherapy has also transformed the treatment landscape of malignancies such as melanoma, among others. However, these advances have not brought meaningful benefits for patients with ACC. Extensive genomic analyses of ACC have revealed numerous signal transduction pathway aberrations (e.g., insulin growth factor receptor and Wnt/β-catenin pathways) that play a central role in pathophysiology. These molecular alterations have been explored as potential therapeutic targets for drug development. This manuscript summarizes recent discoveries in ACC biology, reviews the results of early clinical studies with targeted therapies, and provides the rationale for emerging treatment strategies such as immunotherapy.


[A simple personal computer-based system for lung sound analysis].
Although lung sounds provide important information about the respiratory system, the analysis of lung sounds has not been widely used in clinical practice because of the complicated procedure involved. However, personal computer technology has made impressive strides in recent years. Today, practically all personal computer models on the market are equipped with the capacity for audio signal input and output. We developed a new computer system for lung sounds acquisition and analysis. The system hardware comprises only a personal computer and a microphone, and the software was developed for a widely used operating system (Windows 95). Our system can record, save, and replay lung sounds and analyze their time and frequency domains. To verify the accuracy of sound acquisition, we examined the frequency characteristics of the system as installed and utilized on 4 different machines. The characteristics were essentially flat throughout the 200-2,000 Hz spectrum within which almost all lung sounds were contained. We feel our system can serve as a simple and useful tool for lung sound analysis.


Design of Novel Aminoglycoside Derivatives with Enhanced Suppression of Diseases-Causing Nonsense Mutations.
New pseudotrisaccharide derivatives of aminoglycosides that exploit additional interaction on the shallow groove face of the decoding-site rRNA of eukaryotic ribosome were designed, synthesized and biologically evaluated. Novel lead structures (6 and 7 with an additional 7'-OH), exhibiting enhanced specificity to eukaryotic cytoplasmic ribosome, and superior nonsense mutation suppression activity than those of gentamicin, were discovered. The comparative benefit of new leads was demonstrated in four different nonsense DNA-constructs underling the genetic diseases cystic fibrosis, Usher syndrome, and Hurler syndrome.