Preventive efficacy of oxidized dextran and pathomorphological processes in mouse lungs in avian influenza A/H5N1.
Oxidized dextran (60 kDa) exerted a pronounced preventive effect in laboratory mice infected with avian influenza subtype H5N1 A/Goose/Krasnoozerskoye/627/05 virus, which manifested in a significant increase in mouse lifetime (by 24.4%) and a decrease in mortality rate (3.3-fold). This was probably related to significant alleviation of pathological changes in the lungs and severity of hemodynamic and inflammatory complications and early fibrosis [corrected].


Biological characterization of ovarian granulosa cell tumours of slaughtered cattle: assessment of cell proliferation and oestrogen receptors.
Of 1489 slaughtered cattle, 11 had ovarian granulosa cell tumours (GCTs). These GCTs were examined immunohistochemically for proliferating cell nuclear antigen (PCNA) and oestrogen receptor (ER) in relation to histopathological features (growth pattern, nuclear atypia and mitotic count). On the basis of nuclear atypia and mitotic count, the prognosis for GCTs with a diffuse growth pattern appeared less favourable than that for GCTs with a follicular or trabecular pattern. Increased PCNA expression was significantly associated with nuclear atypia but not with histological growth pattern or mitotic count. A novel finding was the presence of ERbeta but not ERalpha in bovine ovarian GCTs. However, ERbeta expression did not appear to be related to the histopathological features examined. The results indicate that PCNA expression may be of value in establishing the biological behaviour of bovine GCTs. However, a larger series of bovine GCTs should be examinated to assess the prognostic significance of ERbeta.


Paired pulse analysis of ATP and noradrenaline release from sympathetic nerves of rat tail artery and mouse vas deferens: effects of K+ channel blockers.
1. The paired pulse stimulus paradigm - two pulses of equal strength delivered at variable interpulse intervals was used to study the release of ATP and noradrenaline (NA) from post ganglionic sympathetic nerves of rat tail artery and mouse vas deferens. 2. Excitatory junction currents (EJCs) were used to measure the release of ATP, and differential pulse amperometry to measure that of NA. 3. At interpulse intervals of 0.1 - 1 s paired pulse stimulation caused an increase in the size of the second EJC, both in rat tail artery and mouse vas deferens. As the interpulse interval was increased to 10 s or more, the two EJCs became of equal size. 4. In both preparations the K+ channel blockers tetraethylammonium (TEA, 20 mM) and 4-aminopyridine (4-AP, 1 mM) prolonged the duration of the nerve terminal spike and greatly amplified the first EJC of the pair. 5. In the presence of TEA and 4-AP in rat tail artery paired pulse stimulation caused a dramatic depression of the second EJC without markedly affecting the nerve terminal spike. The depression of the second EJC decreased with increasing interpulse intervals, and also when external Ca2+ was reduced to 0.2 mM. In mouse vas deferens, TEA and 4-AP caused only a modest depression of the second EJC. 6. In rat tail artery in the presence of TEA and 4-AP paired pulse stimulation caused a depression of the NA oxidation current evoked by the second pulse, which was similar in magnitude and time course to that of the EJC. Similar TEA and 4-AP induced depression of the second pulse response was also observed when the purinergic and noradrenergic components of the contractile response were investigated. 7. The results show that in rat tail artery K+ channel blockers cause a dramatic paired pulse depression of the release of ATP and NA. The similarity in the depression of the EJC, the NA oxidation current, and the purinergic and noradrenergic components of the contractile response is compatible with the hypothesis that ATP and NA are released in parallel from the same neuronal sources.


Design of a rapid diagnostic model for bladder compliance based on real-time intravesical pressure monitoring system.
The diagnosis of bladder dysfunction for children depends on the confirmation of abnormal bladder shape and bladder compliance. The existing gold standard needs to conduct voiding cystourethrogram (VCUG) examination and urodynamic studies (UDS) examination on patients separately. To reduce the time and injury of children's inspection, we propose a novel method to judge the bladder compliance by measuring the intravesical pressure during the VCUG examination without extra UDS. Our method consisted of four steps. We firstly developed a single-tube device that can measure, display, store, and transmit real-time pressure data. Secondly, we conducted clinical trials with the equipment on a cohort of 52 patients (including 32 negative and 20 positive cases). Thirdly, we preprocessed the data to eliminate noise and extracted features, then we used the least absolute shrinkage and selection operator (LASSO) to screen out important features. Finally, several machine learning methods were applied to classify and predict the bladder compliance level, including support vector machine (SVM), Random Forest, XGBoost, perceptron, logistic regression, and Naive Bayes, and the classification performance was evaluated. 73 features were extracted, including first-order and second-order time-domain features, wavelet features, and frequency domain features. 15 key features were selected and the model showed promising classification performance. The highest AUC value was 0.873 by the SVM algorithm, and the corresponding accuracy was 84%. We designed a system to quickly obtain the intravesical pressure during the VCUG test, and our classification model is competitive in judging patients' bladder compliance. This could facilitate rapid auxiliary diagnosis of bladder disease based on real-time data. The promising result of classification is expected to provide doctors with a reliable basis in the auxiliary diagnosis of some bladder diseases prior to UDS.


Binding behaviour and conformational properties of globular proteins in the presence of immobilised non-polar ligands used in reversed-phase liquid chromatography.
The thermodynamic and extra-thermodynamic dependencies of five types of cytochrome c in water-acetonitrile mixtures of different composition in the presence of immobilised n-octyl ligands as a function of temperature from 278 K to 338 K have been investigated. The corresponding enthalpic, entropic and heat capacity parameters, deltaHdegrees assoc, deltaS degrees assoc and delta C degrees p, have been evaluated from the observed non-linear Van't Hoff plots of these globular proteins in these heterogeneous systems. The relationships between the free energy dependencies, various molecular parameters and extra-thermodynamic dependencies (empirical correlations) of these protein-non-polar ligand interactions have also been examined. Thus, the involvement of enthalpy-entropy compensation effects has been documented for the binding of these cytochrome cs to solvated n-octyl ligands. Moreover, the results confirm that this experimental approach permits changes in molecular surface area due to the unfolding of these proteins on association with non-polar ligands as a function of temperature to be correlated with other biophysical properties. This study thus provides a general procedure whereby the corresponding free energy dependencies of globular proteins on association with solvated non-polar ligands in heterogeneous two-phase systems can be quantitatively evaluated in terms of fundamental molecular parameters.


Posterior chordal cutting in rheumatic mitral regurgitation due to hypomobility of the posterior leaflet.
A technique is described for correction of mitral regurgitation when the posterior leaflet has a reasonable length (approximately 10 mm), but its movements are limited by thickened and short chords. To avoid further retraction when a band or a ring is positioned to force leaflets coaptation, native chords are replaced by artificial chords (leaving 10 mm of extra length), which are then cut. In 6 patients, after 6 months of follow-up, the results are good.


Anatomical and functional impairment of the nerve fiber layer in patients with optic nerve head drusen.
To evaluate anatomical and functional impairment of the retinal nerve fiber layer (RNFL) using optical coherence tomography (OCT) and automated perimetry in patients with optic nerve head drusen (ONHD). Sixty-six eyes (66 patients) were studied with ONHD - confirmed by ultrasound B scan - and 70 eyes (70 subjects) of healthy control subjects. ONHD cases were categorised as visible or hidden. Average RNFL thickness and measurements in terms of the quadrants were analysed using both time-domain optical coherence tomography (TD-OCT) and spectral-domain optical coherence tomography (SD-OCT). Anatomical and visual field alteration of RNFL between visible and hidden ONHD and control groups were compared. Average RNFL thickness in ONHD patients was 94 μm (TD-OCT) and 88 μm (SD-OCT), and in controls 107 μm (TD-OCT) and 96 μm (SD-OCT), with statistically significant differences between both OCTs. All quadrants analysed showed significant differences except the temporal quadrant. The differences were not significant between hidden drusen and controls.Visual field examination in ONHD showed alterations in 56 %. Alterations were greater in visible drusen in relation to non-visible drusen, but there were no significant differences.The association between RNFL defects in superior, inferior and temporal quadrants and visual field defects showed a statistical relation with visible ONHD, but not in hidden ONHD. ONHD caused anatomical and functional damage of the RNFL, with a clear association between the alteration in ONHD and visual field defects in visible drusen cases.


Interferon target-gene expression and epigenomic signatures in health and disease.
Multiple type I interferons and interferon-γ (IFN-γ) are expressed under physiological conditions and are increased by stress and infections, and in autoinflammatory and autoimmune diseases. Interferons activate the Jak-STAT signaling pathway and induce overlapping patterns of expression, called 'interferon signatures', of canonical interferon-stimulated genes (ISGs) encoding molecules important for antiviral responses, antigen presentation, autoimmunity and inflammation. It has now become clear that interferons also induce an 'interferon epigenomic signature' by activating latent enhancers and 'bookmarking' chromatin, thus reprogramming cell responses to environmental cues. The interferon epigenomic signature affects ISGs and other gene sets, including canonical targets of the transcription factor NF-κB that encode inflammatory molecules, and is involved in the priming of immune cells, tolerance and the training of innate immune memory. Here we review the mechanisms through which interferon signatures and interferon epigenomic signatures are generated, as well as the expression and functional consequences of these signatures in homeostasis and autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis.


A systematic review of behavioral interventions for rural breast cancer survivors.
Rural breast cancer survivors (RBCS) are at greater risk for poorer health outcomes and face greater treatment barriers compared to their urban counterparts, necessitating behavioral interventions tailored for the unique needs of RBCS. A systematic review of studies examining behavioral interventions delivered to RBCS living in the United States from 2000 to 2020 was conducted following PRIMSA guidelines. Nineteen unique studies were included: eight randomized controlled trials, two matched-control studies, six pre-post intervention feasibility studies, and three post-intervention satisfaction studies. Thirteen interventions aimed to improve psychosocial support, three to improve weight management, and three to improve education. Results indicate interventions' feasibility and acceptability. Six out of eight intervention conditions reported favorable outcomes compared to control conditions, suggesting promise for efficacy. However, variability in intervention objective, duration, delivery, and follow-up timing, and small sample sizes prevent overarching conclusions. Research involving larger sample sizes, higher quality control groups, and longer follow-up data is needed.


Pseudomonas septicaemia. A review of 60 cases observed in a university hospital.
Epidemiological, clinical features and the pathogenesis of 60 cases of pseudomonas septicaemia, observed over a period of 7 years from 1975 to 1981, are described. The mean frequency of occurrence was 0.40 episodes per 1000 admissions and an incidence of 66 per cent was observed in patients with serious underlying diseases, such as haematological malignancies and neoplasia. Thirty-seven patients had received cytotoxic and immunosuppressive therapy and showed a marked leukopenia, and whenever the leukocyte count fell below 2000/mm3, the prognosis was significantly worse. The most common portals of entry were the respiratory and gastrointestinal tracts. The overall mortality was very high (75 per cent) and mainly related to septic shock. Apart from the very high frequency of this complication (24 patients, 40 per cent of all cases), a typical clinical picture, distinguishing pseudomonas from other Gram-negative septicaemias, did not emerge.


A Case-Control Study of Esomeprazole Plus Rebamipide vs. Omeprazole Plus Rebamipide on Post-ESD Gastric Ulcers.
Endoscopic submucosal dissection (ESD) is useful for treating gastric tumors. Several trials have shown the efficacy of 4 or 8 weeks of proton pump inhibitor (PPI) administration for post-ESD ulcers. However, if the size of the post-ESD ulcer is larger than predicted, PPI administration alone might not be sufficient for the ulcer to heal within 4 weeks. There is no report about the efficacy of post-ESD gastric ulcers by esomeprazole. We examined retrospectively the efficacy of a combination therapy of esomeprazole plus rebamipide, a mucosal-protective antiulcer drug, on the acceleration of post-ESD ulcer healing comparing with omeprazole plus rebamipide. We reviewed the medical records of patients who underwent ESD for gastric neoplasia. We conducted a case-control study to compare the healing rates within 4 weeks effected by esomeprazole plus rebamipide (group E) and omeprazole plus rebamipide (group O). The sizes of the artificial ulcers were divided into normal-sized or large-sized. The baseline characteristics did not differ significantly between the two groups except age and sex. Stage S1 disease was observed in 27.6% and 38.7% of patients after 4 weeks of treatment in the group E and O, respectively. In large-sized artificial ulcers, the healing rate of stage S1 in group E is significantly higher than that in group O in 4 weeks.(25% VS 0%:P = 0.02). The safety and efficacy profiles of esomeprazole plus rebamipide and omeprazole and rebamipide are similar for the treatment of ESD-induced ulcers. In large-sized ulcers, esomeprazole plus rebamipide promotes ulcer healing.


Exploring the terminology and descriptions of services that connect children with neurodisability and their families to needed support in the community: a scoping review protocol.
This scoping review aims to fill a gap in knowledge on terminology and descriptions of services that connect children with neurodisability and their families to needed support in the community. Children with neurodisability represent a significant population with a demonstrated need for coordinated support. Patient navigation is a concept that was founded on the principle of coordinating care for patients based on individual needs. Despite the history of patient navigation, a definition for the concept itself is lacking. Moreover, children with neurodisability and their families are not often the target population of such initiatives. It is not known whether existing terminology and descriptions encompass the particular needs of children with neurodisability and their families. This review will examine published, peer-reviewed articles related to navigation-type resources, support, and services within the community as intended for children under the age of 18 years with neurodisability, and their families. All eligible studies pertaining to this context will be examined. A preliminary search was completed to find initial search terms, upon which a full search strategy was developed. Search results yielded from PubMed (NCBI), MEDLINE (Ovid), and CINAHL (EBSCO) were screened to ensure articles were peer-reviewed, published in English from 1990 onward, and relevant to both children with neurodisability/their families and navigation-related resources. A full-text review of relevant articles will be conducted and data extracted using the included extraction tool. Extracted terminology and concepts will be analyzed using a modified grounded theory approach, which will inform a working definition of navigational services and related terms. Open Science Framework: https://osf.io/cbvy9.


Functional convergence of invertebrate and vertebrate cytokine-like molecules based on a similar lectin-like activity.
It is generally accepted that the action of cytokines results from their binding to specific receptors. However, many cytokines possess lectin-like activity that may be essential for the expression of their full biological activities. This review focuses on the physiological relevance of the lectin-like activity of cytokines during the innate immune response in mammals, using TNF as an illustrative example. Moreover, we will show that TNF displays functional analogies with a defense molecule from the earthworm Eisenia foetida termed CCF. These analogies are not reflected by primary sequence homology between CCF and TNF but are particularly based on a similar lectin-like activity/domain. Hence, from a phylogenetic point of view, the lectin-like activity/domain of CCF and TNF may represent an essential recognition mechanism that has been functionally conserved during the innate immune response of invertebrates and vertebrates as a result of convergent evolution.


Identification of subcellular compartments involved in biosynthetic processing of cathepsin D.
We have assigned the biosynthetic processing steps of cathepsin D to intracellular compartments which are involved in its transport to lysosomes in HepG2 cells. Cathepsin D was synthesized as a 51-kDa proenzyme. After formation of 51-55-kDa intermediates due to processing of N-linked oligosaccharides, procathepsin D was proteolytically processed to an intermediate 44-kDa and the mature 31-kDa enzyme. The intersection of the biosynthetic pathway of cathepsin D with the endocytic pathway was labeled with horseradish peroxidase and monitored biochemically by 3,3'-diaminobenzidine cytochemistry. Horseradish peroxidase was used either as a fluid-phase marker to label the entire endocytic pathway or conjugated to transferrin (Tf) to label endosomes only. Directly after biosynthesis cathepsin D was accessible neither to horseradish peroxidase nor Tf-horseradish peroxidase. Newly synthesized 51-55-kDa species of cathepsin D present in the trans-Golgi reticulum were accessible to both horseradish peroxidase and Tf-horseradish peroxidase. The accessibility of trans-Golgi reticulum to both endocytosed horseradish peroxidase and Tf-horseradish peroxidase was monitored by colocalization with a secretory protein, alpha 1anti-trypsin. The proteolytic processing of 51-55-kDa to 44-kDa cathepsin D occurred in compartments which were fully accessible to fluid-phase horseradish peroxidase. Tf-horseradish peroxidase had access to only 20% of 44-kDa cathepsin D while it had no access to 31-kDa cathepsin D. In contrast, the 31-kDa species was completely accessible to fluid-phase horseradish peroxidase. We conclude that proteolytic processing of 51-55-kDa to 44-kDa cathepsin D occurs in endosomes, whereas the processing of 44-31-kDa cathepsin D takes place in lysosomes.


Fever in the immunocompromised host.
A broad classification of immune defects provides a framework for the approach to fever in the immunocompromised host. Practical, historical, and physical examination findings are reviewed, and common clinical scenarios are highlighted. A general initial work-up and treatment plan are outlined.


The Accuracy of Mammography, Ultrasound, and Magnetic Resonance Imaging For the Measurement of Invasive Breast Cancer With Extensive Intraductal Components.
The precise preoperative evaluation of radiologic tumor size with extensive intraductal component (EIC) is important. This study compared the accuracy of mammography, ultrasound (US), and magnetic resonance imaging (MRI) to measure invasive breast cancer with EIC. Between 2007 and 2012, we collected data from 6816 patients who underwent surgery for invasive breast cancer at our institution. We reviewed the postoperative surgical reports of the tumors, in which the invasive tumor size and EIC were measured separately. Finally, we included 370 women who underwent preoperative mammography, US, and MRI. Each modality was retrospectively reviewed to measure the size of invasive breast cancer with EIC. The reference standard was surgical pathologic size and the accuracies of the image were evaluated. Spearman's correlation coefficient for the size of invasive cancer with EIC was good between MRI (r = 0.741) and pathology, and moderate between mammography (r = 0.661) or US (r = 0.514) and pathology. Both mass and nonmass lesions showed good correlations (intraclass correlation coefficient [ICC] = 0.672 and 0.612, respectively) in MRI. Furthermore, the subgroup of tumors without microcalcifications showed a higher correlation with MRI (ICC = 0.796) than with mammography (ICC = 0.620). However, the subgroup with microcalcifications showed a good correlation with mammography (ICC = 0.702) compared to MRI (ICC = 0.680) and US (ICC = 0.532). The lesion on mammography, US, and MRI reflected preoperative size of invasive cancer with EIC. MRI shows a higher correlation than mammography and US. However, cancer with calcifications of mammography shows a more accurate size than MRI or US.


Observing the interplay between surface and bulk optical nonlinearities in thin van der Waals crystals.
Van der Waals materials, existing in a range of thicknesses from monolayer to bulk, allow for interplay between surface and bulk nonlinearities, which otherwise dominate only at atomically-thin or bulk extremes, respectively. Here, we observe an unexpected peak in intensity of the generated second harmonic signal versus the thickness of Indium Selenide crystals, in contrast to the quadratic increase expected from thin crystals. We explain this by interference effects between surface and bulk nonlinearities, which offer a new handle on engineering the nonlinear optical response of 2D materials and their heterostructures.


Medical end-of-life decisions in Switzerland 2001 and 2013: Who is involved and how does the decision-making capacity of the patient impact?
In Switzerland, the prevalence of medical end-of-life practices had been assessed on a population level only once - in 2001 - until in 2013/14 an identical study was conducted. We aimed to compare the results of the 2001 and 2013 studies with a special focus on shared decision-making and patients' decision-making capacity. Our study encompassed a 21.3% sample of deaths among residents of the German-speaking part of Switzerland aged 1 year or older. From 4998 mailed questionnaires, 3173 (63.5%) were returned. All data were weighted to adjust for age- and sex-specific differences in response rates. Cases with at least one reported end-of-life practice significantly increased from 74.5% (2001) to 82.3% (2013) of all deaths eligible for an end-of-life decision (p <0.001). In 51.2% there was a combination of at least two different end-of-life decisions in one case. In relation to discussion with patients or relatives and otherwise expressed preferences of the patient, 76.5% (74.5-78.4%) of all cases with reported medical end-of-life practice in 2013 (2001: 74.4%) relied on shared decision-making, varying from 79.8% (76.5-82.7%) among not at all capable patients to 87.8% (85.0-90.2%) among fully capable patients. In contrast to a generally increasing trend, the prevalence of end-of-life practices discussed with fully capable patients decreased from 79.0% (75.3-82.3%) in 2001 to 73.2% (69.6-76.0%) in 2013 (p = 0.037). Despite a generally high incidence of end-of-life practices in Switzerland, there remains potential for further improvement in shared decision-making. Efforts to motivate physicians to involve patients and relatives may be a win-win situation.


GENETIC DIVERSITY, PARENTAGE VERIFICATION AND GENETIC BOTTLENECKS EVALUATION IN IRANIAN TURKMEN HORSE BREED.
The present study was undertaken to genetically evaluate Turkmen horses for genetic diversity and to evaluate whether they have experienced any recent genetic bottlenecks. A total of 565 individuals from Turkmen horses were characterized for within breed diversity using 12 microsatellite markers. The estimated mean allelic diversity was (9.42 ± 1.78) per locus, with a total of 131 alleles in genotyped samples. A high level of genetic variability within this breed was observed in terms of high values of effective number of alleles (4.70 ± 1.36), observed heterozygosity (0.757 ± 0.19), expected Nei's heterozygosity (0.765 ± 0.13), and polymorphism information content (0.776 ± 0.17). The estimated cumulative probability of exclusion of wrongly named parents (PE) was high, with an average value of 99.96% that indicates the effectiveness of applied markers in resolving of parentage typing in Turkmen horse population. The paternity testing results did not show any misidentification and all selected animals were qualified based on genotypic information using a likelihood-based method. Low values of Wright's fixation index, F(IS) (0.012) indicated low levels of inbreeding. A significant heterozygote excess on the basis of different models, as revealed from Sign and Wilcoxon sign rank test suggested that Turkmen horse population is not in mutation-drift equilibrium. But, the Mode-shift indicator test showed a normal 'L' shaped distribution for allelic class and proportion of alleles, thus indicating the absence of bottleneck events in the recent past history of this breed. Further research work should be carrying out to clarify the cause of discrepancy observed forbottleneck results in this breed. In conclusion, despite unplanned breeding in Turkmen horse population, this breed still has sufficient genetic variability and could provide a valuable source of genetic material that may use for meeting the demands of future breeding programs.


Crassulacean acid metabolism in the seasonally submerged aquatic Isoetes howellii.
Evidence to date is consistent with the hypothesis that the submerged aquatic Isoetes howellii Engelmann possesses crassulacean acid metabolism. Quantitative 14C uptake studies indicate that CO2 assimilation in both the light and dark are functions of pH and total inorganic carbon level. In both the light and dark, maximum uptake rates in 0.6 mM NaHCO3 were double the rates in 0.3 mM NaHCO3. At both carbon levels there was a large drop in carbon assimilation rate between pH 6 and 8. In nature water pH and inorganic carbon level fluctuated diurnally thus complicating the determination of the contribution of light vs dark CO2 uptake to the total carbon gain. On a sunny day between 0600 and 1200 h water chemistry changed markedly with ∼40% reduction in total carbon, ∼2 pH unit rise resulting from ∼100% depletion of free CO2. Under such conditions daytime deacidification in Isoetes leaves was 88% complete by noon. In contrast, on an overcast day, reduction of carbon in the water was much slower, deacidification was only 46% complete by noon and substantial malic acid levels remained in the leaves at the end of the day. Upon emergence crassulacean acid metabolism was largely lost in Isoetes leaves. Preliminary estimates suggest that under natural submerged conditions, early morning photosynthetic rates may be substantially higher than dark CO2 uptake rates, though uptake rates throughout much of the day could be substantially lower than nightime CO2 assimilation.


Antibiotic associated colitis.
It is a prospective study based on 100 consecutive cases of diarrhea following antibiotic therapy admitted to the pediatric services of J.N. Medical College, A.M.U., Aligarh between January to December 1987. They had C. penicillin (50), chloramphenicol (34), ampicillin (34), gentamicin (34), cephalosporin (4) and cotrimoxazole (4) for 3 days to 3 weeks prior to the onset of diarrhea. Apart from routine and special investigations, naked eye and microscopic examination of stool, its culture for pathogens including Cl. difficile were carried out in all cases. Presence of Cl. difficile cytotoxin was demonstrated by observing the cytopathic. Effect on veru cell culture, 18 grew Cl. difficile (14 cyto toxin positive). Frequency of fever, vomiting, abdominal distension, dehydration and duration of diarrhea was not different (p > 0.05) in the two groups. Purge rate and presence of mucus and blood in Cl. difficile positive patients was significantly higher (p < 0.05). Eight Cl. difficile positive (7 cytotoxin+ve) were subjected to endoscopy. Three of them showed P.M. colitis and 2 non specific colitis. Chloromycetin, gentamicin and penicillin were the main culprits responsible for AAC. None of the patients given ampicillin alone suffered from AAC. The mortality was 5%.


Endoscopic management with inside stent for proximal benign biliary stricture after laparoscopic cholecystectomy.
Endoscopic placement of a plastic stent is the standard drainage for a symptomatic benign biliary stricture. Although a removable fully covered self-expandable metal stent has been applied for distal benign biliary stricture, placement of a plastic stent remains the standard treatment for proximal benign biliary stricture. Placement of a plastic stent above the papilla (inside stent) is an alternative to the conventional method because of its preventive effect against the dysfunction of the stent in patients with proximal benign biliary stricture.


Low-load behaviour of the patellar tendon graft and its relevance to the biomechanics of the reconstructed knee.
Although the linear elastic (high-load) properties of patellar tendon graft used for anterior cruciate ligament (ACL) reconstruction are studied extensively, the low-load properties of the graft, associated with the toe region of its load-deformation curve, are largely neglected. The objectives of this study were to (i) determine the properties of the patellar tendon in the low-load region and compare to that of the intact ACL, (ii) assess the extent of variability in these properties and relate them to donor factors, and (iii) establish the theoretical importance of low-load properties to the function of the reconstructed knee. The patellar tendons of 20 unpaired fresh frozen human knees (10 males and 10 females) were harvested. The central portions were trimmed, measured, and tested in tension to failure. The stress-strain curves were fitted with a bi-linear model and the graft properties were measured. The low-load region modulus of elasticity, E 0, of the patellar tendon, ranged from 49 MPa to 276 MPa in males and 63 MPa to 279 MPa in females. The strain at which the graft transitions from its low-load region to its linear elastic region (epsilon* approximately 4.6%) is on average above the strain levels experienced by the ACL during daily activities (epsilon approximately 4%). Donor sex, height and body mass were found to significantly affect some of the mechanical properties of the low-load region. The results suggest that the low-load region properties of the patellar tendon, not the linear elastic properties, govern the biomechanics of the tibiofemoral joint during the early healing period. Also, a wide variability of graft properties in the low-load region exists partly due to certain donor factors. Clinicians should be aware of the low-load region behaviour of the graft and its influence on time=0 behaviour of the reconstructed knee.


Increased prevalence of radiological spinal deformities in active acromegaly: a cross-sectional study in postmenopausal women.
This cross-sectional study shows that high numbers of postmenopausal women with acromegaly develop vertebral fractures in relation to the activity of disease. In patients with active acromegaly, vertebral fractures occur even in presence of normal BMD, whereas in patients with controlled acromegaly, vertebral fractures are always accompanied by a pathological BMD. We studied the frequency of radiological vertebral fractures in a cohort of postmenopausal women with active or controlled acromegaly. Thirty-six postmenopausal acromegalic patients (15 with active and 21 with controlled disease) were evaluated for BMD, bone metabolism (serum 25-hydroxyvitamin D, PTH, bone-specific alkaline phosphatase [BSALP], and urinary deoxypyridinoline [Dpd]), and vertebral quantitative morphometry. Thirty-six nonacromegalic postmenopausal women, matched for age, were selected among the patients consulting the Bone Center as a control group for BMD evaluation and vertebral quantitative morphometry. Vertebral fractures were shown in 19 patients (52.8%) and 11 controls (30.6%; chi2: 3.7; p=0.06). Fractured acromegalic women were older and had higher serum IGF-1, Dpd, and BSALP and lower T score and serum vitamin D values compared with nonfractured patients. Moreover, the fractured women had a longer diagnosis and were in the postmenopausal period for a longer period than the nonfractured women. The fracture rate was significantly higher in active than in controlled acromegaly (80% versus 33.3%; chi2: 7.6; p=0.008). The patients with active acromegaly who fractured (12 cases) had significantly higher serum IGF-1 values (356 ng/ml; range: 212-950 versus 120 ng/ml; range: 84-217; p<0.001) and T scores (-1.3 SD, range: -2.9 to +1.3 versus -2.7 SD, range: -3.4 to -1.5, p=0.04) compared with the fractured women whose disease was controlled (7 cases). All fractured women with controlled acromegaly had T scores<-1.0 SD (57.1% of them had osteoporosis, and 42.9% were osteopenic). In contrast, 41.7% of women whose fractures were associated with active disease had a normal T score (>-1.0 SD), whereas osteopenia and osteoporosis were found only in 33.3% and 25.0% of them, respectively. This cross-sectional study shows that high numbers of postmenopausal women with acromegaly develop vertebral fractures in relation to the activity of disease. Furthermore, our study shows that, in patients with active acromegaly, vertebral fractures occur even in the presence of normal BMD, whereas in patients with controlled acromegaly, vertebral fractures are always accompanied by a pathological BMD.


The influence of bedding materials on bio-aerosol exposure in dairy barns.
Bio-aerosol is a well-known cause of respiratory diseases. Exposure to bio-aerosols has been reported previously in dairy barns, but little is known about the sources of bio-aerosol. Bedding materials might be a significant source or substrate for bio-aerosol exposure. The aim of this study was to explore bio-aerosol exposure levels and its determinants in dairy barns with various bedding materials. Dust samples were collected at dairy barns using various bedding materials. Samples were analyzed for endotoxin and β(1 → 3)-glucan contents. Culturable bacteria and fungi were sampled by the Anderson N6 impactor. Exposure models were constructed using linear mixed models. The personal exposure levels to dust, endotoxin, and β(1 → 3)-glucan differed significantly between the barns utilizing diverse main bedding types (P<0.05), with the highest levels (GM: dust, 1.38 mg/m(3); endotoxin, 895 EU/m(3); β(1 → 3)-glucan, 7.84 μg/m(3)) in barns with compost bedding vs the lowest in barns with sawdust bedding (GM: dust, 0.51 mg/m(3); endotoxin, 183 EU/m(3); β(1 → 3)-glucan, 1.11 μg/m(3)). The exposure levels were also highly variable, depending on various extra bedding materials applied. Plant materials, particularly straw, utilized for bedding appeared to be a significant source for β(1 → 3)-glucan. Compost was significantly associated with elevated exposure levels. Between-worker variances of exposure were highly explained by determinants of exposure like type of bedding materials and milking by robot, whereas determinants could explain to lesser extent the within-worker variances. Exposure levels to endotoxin, β(1 → 3)-glucan, bacteria, and fungi in dairy barns were substantial and differed depending on bedding materials, suggesting bedding material types as a significant predictor of bio-aerosol exposure.


Therapeutic application of calcium-channel antagonists for pulmonary hypertension.
Calcium-channel antagonists may provide an effective approach to the treatment of pulmonary hypertensive disorders. Biochemical evidence suggests that pulmonary vasoconstriction results from the transmembrane flux of calcium into vascular smooth muscle; accordingly, the pulmonary pressor responses in experimental hypoxic pulmonary hypertension can be attenuated by verapamil and nifedipine. In patients with chronic obstructive lung disease, nifedipine decreases pulmonary artery pressures and pulmonary vascular resistance in proportion to the severity of hypoxemia before treatment. However, little pulmonary vasodilator effect is seen when hypoxemia is corrected by inhalation of oxygen, and systemic arterial oxygen desaturation can occur after nifedipine in patients breathing room air; most importantly, long-term studies in patients with chronic lung disease are lacking. In selected patients with primary pulmonary hypertension and other obliterative diseases of the pulmonary vasculature, nifedipine produces short- and long-term hemodynamic improvement at rest and during exercise, and these benefits are frequently paralleled by amelioration of dyspnea and fatigue. However, in patients in whom right ventricular function has been severely compromised by chronic pressure overload, both verapamil and nifedipine may exert notable depressant effects on right ventricular performance, despite the decrease in right ventricular afterload that would be expected to accompany a decrease in pulmonary vascular resistance. These negative inotropic actions may result in serious deleterious clinical reactions. Although calcium-channel antagonists represent a promising approach to the management of patients with pulmonary hypertension, the long-term efficacy and safety of these drugs in this disorder remain to be established.


Changes in Reward after Gastric Bypass: the Advantages and Disadvantages.
Gastric bypass surgery is an effective long-term weight loss intervention. Key to its success appears a putative shift in food preference away from high-energy-density foods associated with a reduced appetitive drive and loss of neural reactivity in the reward system of the brain towards food. Post-prandial exaggerated satiety gut hormone responses have been implicated as mediators. Whilst the positive impact of bariatric surgery on both physical and psychological outcomes for many patients is clearly evident, a subset of patients appear to be detrimentally affected by this loss of reward from food and by a lack of alternative strategies for regulating affect after surgery. Mindfulness training has emerged as a potential tool in reducing the need for immediate reward that underpins much of eating behaviour. Further research is needed to help identify patients who may be more vulnerable after gastric bypass and which forms of support may be most beneficial.


Cloning of a cDNA encoding a group-V (group-IX) allergen isoform from rye-grass pollen that demonstrates specific antigenic immunoreactivity.
We have isolated and characterized the cDNA clone, 19R, that encodes an isoform of a major rye-grass pollen allergen, Lol p V [previously referred to as Lol p 1b; Singh et al., Proc. Natl. Acad. Sci. USA 88 (1991) 1384-1388; and Lol p IX; Suphioglu et al., Lancet 339 (1992) 569-572]. Clone 19R was isolated from a rye-grass pollen cDNA expression library using grass pollen-specific immunoglobulin E (IgE) antibodies (Ab) from an allergic serum pool. The nucleotide (nt) sequence of clone 19R potentially encodes a 33.8-kDa protein of 339 amino acids (aa). It possesses a leader peptide essentially identical to the previously characterized isoform of Lol p V (Lol p VA). This indicates a mature processed 31.3-kDa protein of 314 aa, correlating well with the size of the polypeptides revealed by Western analysis of pollen proteins using IgE Ab affinity purified from recombinant fusion protein (reFP) encoded by clone 19R as solid matrix. There is no N-glycosylation motif. The protein encoded by clone 19R, designated Lol p VB, has 66.4% identity and 80.4% similarity with Lol p VA. However, a Lol p VA-specific monoclonal Ab, FMC A7, does not recognize reFP encoded by clone 19R, indicating that Lol p VB does not share this epitope. Cross-reactivity studies using affinity purified IgE Ab showed that both isoforms share similar allergenic epitopes. Immunoblot analysis using sera from a population of 30 patients showed that 80% possess IgE Ab that recognize both Lol p V isoforms. Variation occurred in the signal intensities of IgE binding.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of 17beta-oestradiol on regional blood flow in anaesthetized pigs.
1. The present study was designed to investigate the effects of 17beta-oestradiol on the mesenteric, renal, iliac and coronary circulations and to determine the mechanisms involved. 2. In pigs anaesthetized with sodium pentobarbitone, changes in blood flow in the superior mesenteric, left renal, left external iliac and left circumflex coronary arteries caused by intravenous infusion of 17beta-oestradiol at constant heart rate and arterial pressure were assessed using electromagnetic flowmeters. 3. In eight pigs, infusion of 2 microg h-1 of the hormone caused an increase in renal, iliac and coronary blood flow without affecting mesenteric blood flow, left ventricular dP/dtmax (rate of change of left ventricular systolic pressure) and filling pressures of the heart. In four pigs, these vasodilator effects were enhanced by graded increases in the dose of the hormone between 1, 2 and 3 microg h-1; the highest dose also caused an increase in mesenteric blood flow. 4. In five pigs, blockade of muscarinic cholinoceptors and adrenoceptors with the intravenous administration of atropine, propranolol and phentolamine did not affect the vasodilator responses caused by infusion of 2 microg h-1 of 17beta-oestradiol. 5. The increases in renal, iliac and coronary blood flow caused by infusion of 2 microg h-1 of 17beta-oestradiol were prevented, respectively, by the injection of Nomega-nitro-L-arginine methyl ester (L-NAME) into the renal artery (five pigs), the iliac artery (five pigs) or the coronary artery (five pigs). In five pigs, all responses were prevented by injection of L-NAME into all three arteries. In two pigs, injection of L-NAME into the mesenteric, renal, iliac and coronary arteries abolished the vasodilator responses to the infusion of 3 microg h-1 of 17beta-oestradiol. 6. The present study shows that intravenous infusion of 2 microg h-1 of 17beta-oestradiol primarily dilated renal, iliac and coronary circulations and that a higher dose of the hormone also caused vasodilatation in the mesenteric vascular bed. The mechanism of these responses was shown to be nitric oxide dependent.


A Quality Improvement Initiative to Reduce Screen Time in a Children's Hospital.
The American Academy of Pediatrics strongly recommends that children age 2 and under should have little to no digital media exposure. However, most children are exposed to regular screen time at home. This may also be true for hospitalized children. Through education and access to alternatives, we aimed to reduce screen exposure in our children's hospital for children 2 and under. Between January 2020 and May 2021, we designed and implemented a quality improvement intervention to educate staff and caregivers on the American Academy of Pediatrics screen time recommendations and offer alternatives for hospitalized children. Our primary aim was to decrease screen time exposure for children age 2 and under by 50% within 12 months of project initiation. Balancing measures included staff perception of workload when using screens and perceived parental acceptance of screens being turned off. During baseline data collection period, screens were on for an average of 63% of the audits. Following interventions, the average was reduced to 40%. The outcome measure met special cause with 8 consecutive points below the center line. There was a significant increase in staff who reported offering screen alternatives after intervention. Staff perception of workload and perceived parental acceptance was unchanged. Through implementation of this quality improvement initiative, we reduced screen time by approximately 37% without impacting staff workload. Most importantly, we were able to educate staff and model best practices for caregivers, which may carry into the home, leading to a reduction of screen time and improved health overall.


Early clinical outcomes after transaxillary versus transfemoral TAVI. Data from the Spanish TAVI registry.
Transaxillary access (TXA) has become the most widely used alternative to transfemoral access (TFA) in patients undergoing transcatheter aortic valve implantation (TAVI). The aim of this study was to compare total in-hospital and 30-day mortality in patients included in the Spanish TAVI registry who were treated by TXA or TFA access. We analyzed data from patients treated with TXA or TFA and who were included in the TAVI Spanish registry. In-hospital and 30-day events were defined according to the recommendations of the Valve Academic Research Consortium. The impact of the access route was evaluated by propensity score matching according to clinical and echocardiogram characteristics. A total of 6603 patients were included; 191 (2.9%) were treated via TXA and 6412 via TFA access. After adjustment (n=113 TXA group and n=3035 TFA group) device success was similar between the 2 groups (94%, TXA vs 95%, TFA; P=.95). However, compared with the TFA group, the TXA group showed a higher rate of acute myocardial infarction (OR, 5.3; 95%CI, 2.0-13.8); P=.001), renal complications (OR, 2.3; 95%CI, 1.3-4.1; P=.003), and pacemaker implantation (OR, 1.6; 95%CI, 1.01-2.6; P=.03). The TXA group also had higher in-hospital and 30-day mortality rates (OR, 2.2; 95%CI, 1.04-4.6; P=.039 and OR, 2.3; 95%CI, 1.2-4.5; P=.01, respectively). Compared with ATF, TXA is associated with higher total mortality, both in-hospital and at 30 days. Given these results, we believe that TXA should be considered only in those patients who are not suitable candidates for TFA.


Use of composite resin for restorative and orthodontic correction of anterior interdental spacing.
Anterior diastemas are common esthetic problems. With the advent of superior composite resin materials, the acid-etch/composite resin technique can be used to provide a conservative and practical approach to the closure of interdental spacing. Retention of orthodontically closed spaces can also be achieved more easily through the use of resin-bonded lingual retainers.


Synaptic transmission: inhibition of neurotransmitter release by botulinum toxins.
Botulinum toxin type A, a protein long used in the successful treatment of various dystonias, has a complex mechanism of action that results in muscle relaxation. At the neuromuscular junction, the presynaptic nerve ending is packed with synaptic vesicles filled with acetylcholine, and clustered at the tip of the folds of the postsynaptic muscle membrane are the acetylcholine receptors. Synaptic vesicles fuse with the membrane in response to an elevation of intraneuronal calcium concentration and undergo release of their transmitter by exocytosis. Intracellular proteins that contribute to the fusion of the vesicles with the plasma membrane during exocytosis include synaptosomal protein with a molecular weight of 25 kDa (SNAP-25); vesicle-associated membrane protein (VAMP), also known as synaptobrevin; and syntaxin. Through their proteolytic action on these proteins, botulinum toxins prevent exocytosis, thereby inhibiting the release of acetylcholine. There are 7 serotypes of this toxin-A, B, C1, D, E, F, and G-and each cleaves a different intracellular protein or the same target at distinct bonds. The separate cleavage sites in SNAP-25 for botulinum toxin types A and E contribute to their dissimilar durations of muscle relaxation. This report describes the molecular basis for the inhibition by botulinum toxins of neuroexocytosis and subsequent functional recovery at the neuromuscular junction.


Promoter-proximal nucleosomes attenuate RNA polymerase II transcription through TFIID.
A nucleosome is typically positioned with its proximal edge (NPE) ∼50 bp downstream from the transcription start site of metazoan RNA polymerase II promoters. This +1 nucleosome has distinctive characteristics, including the presence of variant histone types and trimethylation of histone H3 at lysine 4. To address the role of these features in transcription complex assembly, we generated templates with four different promoters and nucleosomes located at a variety of downstream positions, which were transcribed in vitro using HeLa nuclear extracts. Two promoters lacked TATA elements, but all supported strong initiation from a single transcription start site. In contrast to results with minimal in vitro systems based on the TATA-binding protein (TBP), TATA promoter templates with a +51 NPE were transcriptionally inhibited in extracts; activity continuously increased as the nucleosome was moved downstream to +100. Inhibition was much more pronounced for the TATA-less promoters: +51 NPE templates were inactive, and substantial activity was only seen with the +100 NPE templates. Substituting the histone variants H2A.Z, H3.3, or both did not eliminate the inhibition. However, addition of excess TBP restored activity on nucleosomal templates with TATA promoters, even with an NPE at +20. Remarkably, nucleosomal templates with histone H3 trimethylated at lysine 4 are active with an NPE at +51 for both TATA and TATA-less promoters. Our results strongly suggest that the +1 nucleosome interferes with promoter recognition by TFIID. This inhibition can be overcome with TBP alone at TATA promoters or through positive interactions with histone modifications and TFIID.


Identification of an intermediate of delta-aminolevulinate biosynthesis in Chlamydomonas by high-performance liquid chromatography.
The first committed intermediate of the chlorophyll biosynthetic pathway is delta-aminolevulinic acid (ALA). In plant cells, ALA is formed from glutamate by a pathway not yet clearly defined. One of the proposed pathways involves the reduction of glutamate to glutamate-1-semialdehyde (GSA) via a glutamyl-tRNA intermediate. GSA is then converted to ALA by an aminotransferase. We are studying this pathway using partially purified components from Chlamydomonas reinhardtii in in vitro reactions with [3H]L-glutamate as the substrate and analysis of the radioactive reaction products via HPLC. In reactions either lacking GSA-aminotransferase or containing gabaculine (an inhibitor of aminotransferase), a radioactive intermediate is formed which cochromatographs with synthetic GSA. As observed previously for ALA synthesis, the synthesis of this intermediate has an absolute requirement for RNA, ATP, and active enzymes, while the requirement for NADPH is less stringent. Both the accumulated intermediate and the synthetic GSA can be converted to ALA by the aminotransferase without any additional substrates or cofactors. These results support previous observations that GSA or a very similar compound is an intermediate of ALA synthesis.


Lifestyle behavior interventions with Hispanic children and adults.
Chronic diseases are the leading causes of death and disability in the United States and account for 7 of every 10 deaths. While the etiology of chronic diseases is multifactorial, individual modifiable behaviors play an important role in both risk and prevention. Hispanics are disproportionately affected by chronic diseases and are a growing and significant population. The purpose of this chapter is to analyze and critique behavioral lifestyle interventions conducted with adolescent and adult Hispanics. Specific recommendations for continued research and policy are provided.


Experimental studies on immunosuppressive effects of peste des petits ruminants (PPR) virus in goats.
Effect of virulent and attenuated peste des petits ruminants (PPR) virus on the immune response to nonspecific antigen (ovalbumin) was investigated. Clinical and serological responses were monitored in goats administered with ovalbumin concurrently with either PPR vaccine or virulent virus. Study showed that PPR virulent virus causes marked immunosuppression as evidenced by leukopenia, lymphopenia, and reduced early antibody response to both specific and nonspecific antigen. These observations were predominant particularly during acute phase of disease (4-10 days post-infection). On the other hand, the vaccine virus induced only a transient lymphopenia without significantly affecting the immune response to nonspecific antigen or to itself during this period. Further, the antibody levels to ovalbumin in the group administered with virulent PPRV increased significantly between days 28 and 35 post-infection in comparison to the titers in other two groups given with either ovalbumin alone or in combination with vaccine.


DOPA-mediated reduction allows the facile synthesis of fluorescent gold nanoclusters for use as sensing probes for ferric ions.
In this paper, we describe a simple one-pot method, employing l-3,4-dihydroxyphenylalanine (L-DOPA) as a reducing/capping reagent, for the synthesis of fluorescent gold nanoclusters (AuNCs). Within a short reaction time of 15 min (excluding the time required for purification), this strategy allows the fabrication of homogeneous AuNCs having the capability to sense ferric ions (Fe(3+)). The as-prepared AuNCs exhibited a fluorescence emission at 525 nm and a quantum yield of 1.7%. On the basis of an aggregation-induced fluorescence quenching mechanism, these fluorescent AuNCs offer acceptable sensitivity, high selectivity, and a limit of detection of 3.5 μM for the determination of Fe(3+) ions, which is lower than the maximum level (0.3 mg L(-1), equivalent to 5.4 μM) of Fe(3+) permitted in drinking water by the U.S. Environmental Protection Agency.


Heparin inhibits BMP-2 osteogenic bioactivity by binding to both BMP-2 and BMP receptor.
Heparin demonstrates several kinds of biological activities by binding to various extracellular molecules and plays pivotal roles in bone metabolism. However, the role of heparin in the biological activity of bone morphogenetic protein (BMP) remains unclear. In the present study, we examined whether heparin has the effects on osteoblast differentiation induced by BMP-2 in vitro and also elucidated the precise mechanism by which heparin regulates bone metabolism induced by this molecule. Our results showed that heparin inhibited alkaline phosphatase (ALP) activity and mineralization in osteoblastic cells cultured with BMP-2. Heparin was found to suppress the mRNA expressions of osterix, Runx2, ALP and osteocalcin, as well as phosphorylation of Smad1/5/8 and p38 MAPK. Further, heparin bound to both BMP-2 and BMP receptor (BMPR). These results suggest that heparin suppresses BMP-2-BMPR binding, and inhibits BMP-2 osteogenic activity in vitro.


Introducing new group leaders: Sahar Melamed.
Sahar Melamed spoke with Molecular Cell about his interdisciplinary group at the Hebrew University of Jerusalem, which applies experimental and computational approaches to studying regulatory RNAs in bacteria. He talks about the development of RIL-seq to study sRNAs, his approach to applying for academic positions, and the importance of believing in yourself.


Chemoselective ligation reactions with proteins, oligosaccharides and cells.
Traditional chemical synthesis does not lend itself to the easy, rapid construction of even moderately sized biomolecules, because it requires elaborate protection schemes. Furthermore, many biological studies would be aided by the ability to assemble biomolecules under physiological conditions. These challenges have motivated the development of chemoselective ligation, the selective covalent coupling of mutually and uniquely reactive functional groups under mild, aqueous conditions. This technique has attracted significant attention recently for the synthesis of biological macromolecules of defined homogeneous composition, the design of self-assembling drugs and the chemical remodeling of cell surfaces.


Prosthodontic treatment and retreatment of 845 servicemen.
Results of the fixed prosthodontic treatment of 845 servicemen have been shown. Similar to other studies, most crowns were placed in the maxilla. Differences and similarities to other studies were found regarding the fixed prosthodontic treatment per tooth type. The fact that 15% of the crowns placed in the period 1958 to 1977 needed retreatment should be a subject for further analysis.


Characterization of mammalian neurofilament subunits by circular dichroism.
Critical steps in the disassembly and reassembly of neurofilaments, the intermediate filaments of neurons, have been investigated. Bovine neurofilament subunits (Mr 210 000, 160 000 and 70 000) were purified by urea-polyacrylamide gel electrophoresis and renatured by dialysis against several non-denaturing buffers. The quality of the protein renaturation was measured by circular dichroism. The spectra of renatured neurofilament subunits were interpreted in terms of secondary structure and this showed that the solubilization of proteins in guanidine-HCl buffers is more suitable than in urea buffer for a good recovery of a filamentous structure. Furthermore, it is shown that (i) the three neurofilament subunits exhibit specific CD spectra, with shapes reminiscent of those obtained for the alpha/beta class of proteins and that (ii) there is good correlation between CD spectra, the state of renaturation and the ability of the proteins to assemble into filamentous structures. We conclude that CD studies of neurofilament proteins should help in understanding the numerous variables affecting the disassembly and reassembly of neurofilaments.


Epigenomics and bolting tolerance in sugar beet genotypes.
In sugar beet (Beta vulgaris altissima), bolting tolerance is an essential agronomic trait reflecting the bolting response of genotypes after vernalization. Genes involved in induction of sugar beet bolting have now been identified, and evidence suggests that epigenetic factors are involved in their control. Indeed, the time course and amplitude of DNA methylation variations in the shoot apical meristem have been shown to be critical in inducing sugar beet bolting, and a few functional targets of DNA methylation during vernalization have been identified. However, molecular mechanisms controlling bolting tolerance levels among genotypes are still poorly understood. Here, gene expression and DNA methylation profiles were compared in shoot apical meristems of three bolting-resistant and three bolting-sensitive genotypes after vernalization. Using Cot fractionation followed by 454 sequencing of the isolated low-copy DNA, 6231 contigs were obtained that were used along with public sugar beet DNA sequences to design custom Agilent microarrays for expression (56k) and methylation (244k) analyses. A total of 169 differentially expressed genes and 111 differentially methylated regions were identified between resistant and sensitive vernalized genotypes. Fourteen sequences were both differentially expressed and differentially methylated, with a negative correlation between their methylation and expression levels. Genes involved in cold perception, phytohormone signalling, and flowering induction were over-represented and collectively represent an integrative gene network from environmental perception to bolting induction. Altogether, the data suggest that the genotype-dependent control of DNA methylation and expression of an integrative gene network participate in bolting tolerance in sugar beet, opening up perspectives for crop improvement.


The effects of bovine tick resistance on the susceptibility of Hyalomma anatolicum anatolicum to infection with Theileria annulata (Ankara).
Two Bos taurus calves were made resistant to tick infestation by exposing them to approximately 500 rabbit-reared nymphs of Hyalomma anatolicum anatolicum twice at a 2-week interval. These two calves, together with a tick-susceptible control calf, were inoculated with a stabilate of Theileria annulata (Ankara). Patent infection resulted in all three calves. Seven-hundred and fifty gerbil-reared nymphs were then applied on each of these calves as well as another tick-susceptible calf that was Theileria free. This infestation was carried out on Day 8 post-inoculation. Ticks that dropped on Day 13 post-inoculation were examined to note the development of T. annulata in them and the histological changes that occurred in the gut and salivary glands. During the second phase of feeding, the gut epithelia of the ticks from the tick-resistant calves were less active. There were no notable differences in the characteristics of the developmental stages of T. annulata between the ticks from the tick-resistant calves and those from the susceptible calf. However, ticks from one calf that acquired a higher level of tick resistance were significantly less susceptible to infection by T. annulata. Bovine tick resistance therefore compromises the vector capacity of H. a. anatolicum and this may be of epidemiological significance in the endemic areas of tropical theileriosis.


A 6-thioguanine-resistant variant of the 13762 cell line which is no longer tumorigenic or metastatic.
A 6-thioguanine resistant (TGR) variant of the highly tumorigenic and metastatic mammary adenocarcinoma cell line 13762 was obtained. This variant was no longer tumorigenic or metastatic in normal syngeneic rats but did grow as a primary tumor in irradiated animals. Our results suggest that the TGR cell line was rejected by an irradiation-sensitive immunological mechanism. Although the TGR cells produced primary tumors in irradiated animals, there was no evidence of the extensive metastasis seen with the 13762 cells. This apparent inability to metastasize was confirmed by injecting the TGR cells intravenously. Whereas the 13762 cells produced large numbers of metastatic lung foci, there was no evidence of lung metastasis with the TGR cells, even in irradiated animals. Revertant cells for the 6-thioguanine-resistant phenotype were still non-tumorigenic and non-metastatic in normal rats, suggesting that 6-thioguanine resistance is not associated with the altered tumorigenic phenotype. From the TGR variant, cell lines were selected with an increased ability to produce tumors in normal rats. Although some of these revertants were capable of producing limited lung metastases in normal animals, extensive metastases were always seen when the cells were injected into irradiated animals. Differences between the 13762 and the TGR variants were also found in their ability to produce plasminogen activator. The TGR cells released far less plasminogen activator in culture than the 13762 cells. This could be a contributing factor in their different metastatic potentials.


The occurrence of the feline "Candidatus Mycoplasma haemominutum" in dog in China confirmed by sequence-based analysis of ribosomal DNA.
In the present study, polymerase chain reaction (PCR) assay was used to detect haemoplasmas (haemotropic bacteria) in 40 clinically healthy pet dogs in Foshan city, Guangdong Province, China, and one dog was found positive. Comparison of its 16S ribosomal DNA (rDNA) sequence with relevant sequences showed that the isolated haemoplasma had greater sequence identity to feline species "Candidatus Mycoplasma haemominutum" (99%) than to "Candidatus Mycoplasma haematoparvum" (95%). This result, for the first time, indicates the presence of the feline "Candidatus Mycoplasma haemominutum" in Chinese dogs and it represents the first survey of its kind in China by using PCR assay. The results indicated that dog may represent one of the hosts for the feline "Candidatus Mycoplasma haemominutum".


Modelling the Relative Abundance of Roe Deer (Capreolus capreolus L.) along a Climate and Land-Use Gradient.
European roe deer (Capreolus capreolus L.) are important given their economic, recreational and ecological value. However, uncontrolled roe deer numbers can result in negative impacts on forest regeneration and agricultural crops, disease transmission and occurrences of deer-vehicle collisions. Information on the abundance and distribution is needed for effective management. We combined distance sampling (DS) of roe deer dung pellet groups with multiple variables to develop a density surface model (DSM) in the federal state of Bavaria in south-eastern Germany. We used the estimates of pellet group density as a proxy for roe deer relative abundance. We extrapolated our best DSM, conducted a quantitative evaluation and contrasted relative abundance along climate and land-use gradients. Relative abundance of roe deer was influenced by a combination of habitat type, climate and wildlife management variables, which differed between seasons and which reflected changes in food and shelter availability. At the landscape scale, the highest abundance was observed in agriculture-dominated areas and the lowest in urban areas. Higher abundance was also observed in areas with intermediate temperatures compared to the warmest areas. Our results provide information on possible future changes in the distribution of relative abundance due to changes in climate and land-use.


Upregulation of centrosomal protein 55 is associated with unfavorable prognosis and tumor invasion in epithelial ovarian carcinoma.
Centrosomal protein 55 (CEP55) is a cell cycle regulator implicated in development of certain cancers. However, characteristics of CEP55 expression and its clinical/prognostic significance are unclear in human epithelial ovarian carcinoma (EOC). Therefore, we investigated the expression and clinicopathological significance of CEP55 in patients with EOC and its role in regulating invasion and metastasis of ovarian cell lines. CEP55 mRNA and protein expression levels were detected by quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemistry (IHC). Potential associations of CEP55 expression scores with clinical parameters and patient survival were evaluated. CEP55 function was investigated further using RNA interference, wound healing assay, transwell assay, immunofluorescence analysis, qRT-PCR, and Western blotting. CEP55 was significantly upregulated in ovarian cancer cell lines and lesions compared with normal cells and adjacent noncancerous ovarian tissues. In the 213 EOC samples, CEP55 protein levels were positively correlated with clinical stage (P < 0.001), lymph node metastasis (P < 0.001), intraperitoneal metastasis (P < 0.001), tumor recurrence (P < 0.001), differentiation grade (P < 0.001), residual tumor size (P < 0.001), ascites see tumor cells (P = 0.020), and serum CA153 level (P < 0.001). Moreover, patients with aberrant CEP55 protein expression showed tendencies to receive neoadjuvant chemotherapy (P < 0.001) and cytoreductive surgery (P = 0.020). By contrast, no significant correlation was detected between the protein levels and patient age, histological type, or serum CA125, CA199, CA724, NSE, CEA, and β-HCG levels. Patients with high CEP55 protein expression had shorter overall survival and disease-free survival compared with those with low CEP55 expression. Multivariate analysis implicated CEP55 as an independent prognostic indicator for EOC patients. Additionally, downregulation of CEP55 in ovarian cancer cells remarkably inhibited cellular motility and invasion. Aberrant CEP55 expression may predict unfavorable clinical outcomes in EOC patients and play an important role in regulating invasion in ovarian cancer cells. Thus, CEP55 may serve as a prognostic marker and therapeutic target for EOC.


The stability of ascorbic acid in TPN mixtures stored in a multilayered bag.
Because of the susceptibility of some vitamins to oxidation, they are not normally added to TPN mixtures until shortly before addministration. Vitamin C (ascorbic acid) is oxidised rapidly, especially in the presence of trace elements. The aim of this study was to investigate the stability of ascorbic acid in complete TPN mixtures in Ultrastab multilayer bags, which are designed to reduce oxygen transmission and thus oxidation, in comparison with standard EVA bags. Ascorbic acid content was determined in two typical TPN mixtures providing 16 g nitrogen, 2000 kilocalories, electrolytes, trace elements and multivitamins, with and without fat emulsion, during storage at 5 degrees C for up to 3 months. In EVA bags ascorbic acid degraded by more than 75% during 24 h and was undetectable in 2-3 days. In contrast, there was a comparatively small initial loss of 15-30% ascorbic acid in mixtures stored in multilayer bags, with little further loss during 1-3 months. Bags containing fat emulsion retained higher concentrations of ascorbic acid after storage compared to those without fat emulsion, but all mixtures in multilayer bags maintained 60-80% ascorbic acid activity after 3 months. Since ascorbic acid is the most oxygen-sensitive vitamin, complete TPN mixtures with vitamins could be compounded in multilayer bags for an extended shelf life, rather than admixing just prior to administration.


Determination of ergot alkaloids in plasma by high-performance liquid chromatography and fluorescence detection.
Liquid chromatographic methods for the determination of ergotamine and methylergometrine in plasma have been developed. The samples are extracted with an organic solvent at pH 9.0 cleaned by extractions and finally injected on an ODS-Hypersil reversed-phase column with acetonitrile-ammonium carbonate buffer as the mobile phase. THe polarity of solvents used for extraction and the mobile phase are varied with the compounds of interest. Ergocristine is used as internal standard for ergotamine, and methysergide for the determination of methylergometrine. The stability of samples and standard solutions for calibration are discussed. Conditions for high selectivity and sensitivity of detection are given. Concentrations down to 100 pg/ml of plasma can be detected with a 3-ml sample.


Key historical study findings questioned in debate over threshold versus linear non-threshold for cancer risk assessment.
This paper demonstrates that the dissertation research of Ray-Chaudhuri (1939, 1944) that was used by Hermann Muller to support his radiation induced gene mutation hypothesis and linear non-threshold (LNT) dose response model during his Nobel Prize Lecture is "uninterpretable" with respect to these issues. The research failed to include essential research design information, resulting in reporting flaws that have never been previously identified. These observations are historically important because this dissertation was used to blunt powerful criticism of Muller's gene mutation research and strongly promoted his advocacy of the LNT model in radiation risk assessment.


Conversion of acid hydrolysate of oil palm empty fruit bunch to L-lactic acid by newly isolated Bacillus coagulans JI12.
Cost-effective conversion of lignocellulose hydrolysate to optically pure lactic acid is commercially attractive but very challenging. Bacillus coagulans JI12 was isolated from natural environment and used to produce L-lactic acid (optical purity > 99.5 %) from lignocellulose sugars and acid hydrolysate of oil palm empty fruit bunch (EFB) at 50 °C and pH 6.0 without sterilization of the medium. In fed-batch fermentation with 85 g/L initial xylose and 55 g/L xylose added after 7.5 h, 137.5 g/L lactic acid was produced with a yield of 98 % and a productivity of 4.4 g/L h. In batch fermentation of a sugar mixture containing 8.5 % xylose, 1 % glucose, and 1 % L-arabinose, the lactic acid yield and productivity reached 98 % and 4.8 g/L h, respectively. When EFB hydrolysate was used, 59.2 g/L of lactic acid was produced within 9.5 h at a yield of 97 % and a productivity of 6.2 g/L h, which are the highest among those ever reported from lignocellulose hydrolysates. These results indicate that B. coagulans JI12 is a promising strain for industrial production of L-lactic acid from lignocellulose hydrolysate.


[Results of treatment of Hodgkin's disease in children. Observation of 203 cases treated with modified MVPP regimen combined with local radiotherapy].
Totally 209 children were treated within 1971-1982. Complete remission was achieved in 95.6%. Recurrence was noted in 36 patients (18.6%); 20 patients (9.9%) died due to progression of the disease and 9 patients (4.4%) because of complications. The first remission remains constantly in 150 patients for 63-206 months, including that after completion of therapy during 45-206 months. Asymptomatic 5- and 10-year survivals are the following: 82.9% and 80.1% respectively; 5- and 10-year survivals 91.9% and 89.8%, respectively. Expanded experience served as base to design a new regimen (introduced in 1988) which is being supposed to reduce untoward reaction by decreasing the number of MVPP cycles and irradiation doses.


High prevalence of adrenal insufficiency in patients with sickle cell disease: results from a community hospital in the U.S.
Despite the low prevalence (0.008%) of adrenal insufficiency (AI) in the general population, this disorder was recently diagnosed in a substantial number of sickle cell disease (SCD) patients at our hospital. The main objective of this study was to assess the prevalence of AI in SCD patients. All adult patients admitted to the Department of Medicine at Interfaith Medical Center from October 2010 to November 2011 were eligible for this retrospective study. Medical records of adult SCD patients hospitalized for painful crisis and who had undergone cosyntropin testing were reviewed. Adult non-SCD patients hospitalized for painful crisis and who had undergone cosyntropin testing served as controls. The result of the cosyntropin test was the primary outcome. The prevalence of positive cosyntropin tests was compared between the 2 groups by using Student's t-test, and odds ratios. 62 adult SCD patients were enrolled in the study. 15 underwent cosyntropin testing and 12 (19.4%) of these patients were found to have AI. AI was also diagnosed in 1 of 1,340 non-SCD patients. The odds ratio for AI in SCD to non-SCD patients [(12/62)/(1,340)] was 259. The odds ratio for the prevalence of AI in SCD patients in our study (19.4%) vs. the general population (approximately 0.008%) was 2,375. AI occurred in 19.4% of SCD patients included in this study. These patients thus have a 2,375-fold higher risk of developing AI than the general population, and a 259-fold greater risk of developing AI than do hospitalized non-SCD patients.


A High-Performance 3-D Imaging Technique Using Simultaneous Azimuth and Elevation Compounding.
A new technique for 3-D imaging with a row-column array (RCA) configuration has been developed. The technique requires an electrostrictive piezoelectric for the active substrate. While the top set of electrodes is connected to RF transmit and receive channels for conventional diverging wave imaging (DWI), the orthogonal bottom set of electrodes is connected to independently controlled variable dc bias channels. By implementing modulated bias patterns compounded across multiple pulses, fine delay control across the bottom elements can be achieved simultaneously with imaging with the top set of electrodes. This resulted in a high-quality two-way focus in both azimuth and elevation. A 20-MHz electrostrictive composite substrate was fabricated, and 64 top ×64 bottom electrodes were patterned and connected to custom beamforming and biasing electronics. The point spread functions were generated in all dimensions, and the -6 dB resolution was measured to be 93 [Formula: see text] axially, [Formula: see text] in the azimuth, and 328 [Formula: see text] in the elevation dimension. This was in good agreement with the simulated resolutions of 80, 273, and 280 [Formula: see text], respectively.


Regenerative wound healing in acute degree III mandibular defects in dogs.
To evaluate the healing events in degree III furcation defects in dogs following the application of the combination of an enamel matrix derivative with a biphasic calcium phosphate (Emdogain Plus). Seventeen degree III furcation defects, 5 mm high and 4 mm wide, were created in 9 dogs. In both groups, the defects were conditioned with EDTA. One defect was treated with Emdogain Plus (n = 9), while the contralateral defect serving as control remained empty (n = 8). The defects in both groups were fully covered by coronally repositioned flaps. After 5 months of healing, histologic and histometric analysis was preformed. A significant amount of new attachment and bone formation was observed in both control and test specimens. However, in a number of control specimens, ankylosis was also observed. In the control and test groups, respectively, the mean new cementum length was 10.8 ± 2.1 mm and 8.6 ± 3.2 mm; the mean periodontal ligament length was 7.6 ± 3.8 mm and 8.1 ± 4.0 mm. The mean new bone height was 4.4 ± 1.3 mm and 4.3 ± 1.6 mm in the control and test groups, respectively. No statistical differences were found between the two groups in terms of amount of cementum, periodontal ligament, and alveolar bone regeneration. The present study failed to show higher amounts of newly formed cementum and bone following treatment of acute degree III mandibular furcation defects following use of Emdogain Plus compared with a coronally advanced flap. Emdogain Plus seems to have a protective role against ankylosis in this type of defect.


Paediatric lower urinary tract rhabdomyosarcoma: a single-centre experience of 30 patients.
To retrospectively analyse the long-term outcome of children with bladder and/or prostate rhabdomyosarcoma who were diagnosed at the authors' institution over the last 17 years. The study comprised 30 children (26 boys and four girls, mean age 5 years, range 15 days to 15 years); 23 had stage III and seven had stage II disease. The initial biopsy showed an embryonal variant in 27 and round-cell sarcoma in three patients. All patients received eight weekly doses of vincristine, actinomycin D and cyclophosphamide (VAC). Subsequent treatment depended upon the response to chemotherapy. Fourteen patients had a complete or partial response to chemotherapy (> 50% reduction in tumour size); they were maintained on VAC chemotherapy for 2 years. Twelve patients in this group survived with no evidence of disease for 7 months to 10 years. Additional therapies were used in three patients, i.e. radical cystectomy in one and external irradiation in two. Sixteen patients had a minimal response to chemotherapy; in six, radical cystectomy was feasible and was followed by one year of chemotherapy. All patients were free of disease for 4-11 years. Radiotherapy was given to the remaining 10 patients; thereafter radical cystectomy became feasible in five while partial cystectomy was possible in three. Only three of these 10 patients survived for 4-11 years. The tumour response to initial chemotherapy can be used to stratify patients into two risk-groups, i.e. low-risk patients with a complete or partial response in whom the bladder could be salvaged, and high-risk patients with a minimal response, in whom intensive treatment should be pursued, with no attempt at bladder salvage.


Iatrogenic dissection in paediatric cardiac surgery.
Iatrogenic dissection due to aortic cannulation is extremely rare. We are reporting here a case of 11-month-old child who developed an iatrogenic aortic dissection during repair of supracardiac total anomalous pulmonary venous connection (TAPVC).


Leukapheresis cells of patients with multiple myeloma collected after mobilization with chemotherapy and G-CSF do not bear Kaposi's sarcoma associated herpesvirus DNA.
The presence of Kaposi's sarcoma associated herpesvirus (KSHV) in bone marrow dendritic cells, in bone marrow biopsies and in dendritic cells of peripheral blood from patients with multiple myeloma (MM) has been reported. These data suggested an association between infection with KSHV and the development of MM. The mobilization of infected cells into leukapheresis products (LP) has also been described. We assessed the LP of 35 patients with MM for the presence of KSHV using a sensitive and specific nested PCR assay, capable of detecting one copy of the virus genome. None of the samples tested revealed positivity for KSHV after amplification and subsequent hybridization with a KSHV-specific probe. Amplification products of approximately the same size as the positive control seen in eight samples did not hybridize with the specific oligonucleotide. No homologies of these products to the KSHV genome could be discovered after sequencing. Therefore we have no evidence that LP of patients with MM bear KSHV, and they can therefore be used as a source for dendritic cells for immunotherapy.


Measuring negative emotional responses to climate change among young people in survey research: A systematic review.
Climate change is a threat to the mental and emotional wellbeing of all humans, but young people are particularly vulnerable. Emerging evidence has found that young people's awareness of climate change and the danger it poses to the planet can lead to negative emotions. To increase our understanding about this, survey instruments are needed that measure the negative emotions young people experience about climate change. (1) What survey instruments are used to measure negative emotional responses to climate change in young people? (2) Do survey instruments measuring young people's negative emotional responses to climate change have evidence of reliability and validity? (3) What factors are associated with young people's negative emotional responses to climate change? A systematic review was conducted by searching seven academic databases on November 30, 2021, with an update on March 31, 2022. The search strategy was structured to capture three elements through various keywords and search terms: (1) negative emotions, (2) climate change, and (3) surveys. A total of 43 manuscripts met the study inclusion criteria. Among the 43 manuscripts, 28% focused specifically on young people, while the other studies included young people in the sample but did not focus exclusively on this population. The number of studies using surveys to examine negative emotional responses to climate change among young people has increased substantially since 2020. Survey instruments that examined worry or concern about climate change were the most common. Despite growing interest in climate change emotions among young people, there is a lack of research on the validity of measures of such emotions. Further efforts to develop survey instruments geared to operationalize the emotions that young people are experiencing in relation to climate change are needed.


Association of sleep-disordered breathing and ventricular arrhythmias in patients without heart failure.
The prevalence and characteristics of sleep-disordered breathing (SDB) in patients with ventricular arrhythmias, such as premature ventricular complexes and ventricular tachycardia, are unknown. Therefore, this study was conducted to evaluate the prevalence of SDB in patients with severe ventricular arrhythmias and normal left ventricular (LV) function. Thirty-five patients (63% men, mean age 57.4 +/- 13.8 years) underwent a sleep study. All patients had ventricular tachycardia or frequent premature ventricular complexes (>or=300/hour) and had been referred to the cardiology department for medication, catheter ablation therapy, or the implantation of a cardioverter-defibrillator. Patients with heart failure with LV ejection fractions <50% were excluded; in the remaining patients, the mean LV ejection fraction was 63.9 +/- 8.0%. Twenty-one patients (60%) had SDB with apnea-hypopnea indexes >or=5/hour, and the average apnea-hypopnea index was 22.7 +/- 17.9/hour. Twelve patients (34%) had moderate to severe SDB, with an average apnea-hypopnea index of 33.6 +/- 16.6/hour. Central dominant sleep apnea was evident in 3 patients with SDB. The average age and body mass index were significantly higher in patients with SDB than in those without SDB (age 62.0 +/- 12.8 vs 50.6 +/- 12.7 years, body mass index 26.3 +/- 4.0 vs 21.2 +/- 2.0 kg/m2). In conclusion, this study found a high prevalence of SDB in patients with ventricular arrhythmias and normal LV function.


dCMP-aminohydrolase activity during early sea urchin development. An example of negative enzyme control during embryogenesis.
In sea urchin, unfertilized eggs have a very high level of dCMP-aminohydrolase (dCMPase) activity, which decreases gradually and at the pluteus stage it is only about a quarter of that found in the unfertilized egg. But in abnormal embryos and in disaggregated cells from embryos, no decrease in the dCMPase activity takes place. To understand the control mechanism involved in this enzyme activity during development, we have analyzed the effect of various drugs which interfere with information transfer, such as actinomycin C, puromycin, 5-azacytidine, 2-thio-uracil and p-fluoro-DL-phenylalanine on dCMPase activity in embryos of Paracentrotus lividus and Sphaerechinus granularis. Among these drugs only actinomycin induces a remarkable increase of the dCMPase activity in embryos with respect to unfertilized eggs. Puromycin has a differential and dose-dependent effect. Other drugs, although they affect normal development and macromolecular synthesis, do not significantly alter the dCMPase activity. On the basis of these results we suggest the presence of a repressor mechanism in the control of dCMP-aminohydrolase level during early embryogenesis of sea urchin.


Platelet function is inhibited by non-selective non-steroidal anti-inflammatory drugs but not by cyclo-oxygenase-2-selective inhibitors in patients with rheumatoid arthritis.
Interaction with platelet function by non-steroidal anti-inflammatory drugs (NSAIDs) is related to the inhibition of cyclo-oxygenase-1 (COX-1). In patients with rheumatoid arthritis (RA), only one of the COX-2-selective NSAIDs (nabumetone) has been demonstrated to spare platelet function partially. To compare the effects of the COX-2-selective inhibitor, meloxicam, with those of the non-selective NSAID, naproxen, on platelet function and thromboxane levels in RA patients. In this randomized, controlled, cross-over trial, 10 RA patients used meloxicam 7.5 mg bid and naproxen 500 mg bid, each during a 2-week period. Washout periods were applied. Before and after each 2-week period of NSAID intake, laboratory studies were performed. Platelet aggregation was significantly less influenced, thromboxane levels were less inhibited (246 vs 117 pg/ml) and bleeding times were less prolonged with meloxicam than with naproxen (3.2 vs 2.3 min). Moreover, the results of all tests during meloxicam exposure were comparable with baseline values. In RA patients, meloxicam, a representative of the selective COX-2 inhibitors, does not interfere with platelet function and thromboxane levels, in contrast with naproxen (a non-selective COX inhibitor).


Osmotic micropumps for drug delivery.
This paper reviews miniaturized drug delivery systems applying osmotic principles for pumping. Osmotic micropumps require no electrical energy and consequently enable drug delivery systems of smallest size for a broad field of new applications. In contrast to common tablets, these pumps provide constant (zero-order) drug release rates. This facilitates systems for long term use not limited by gastrointestinal transit time and first-pass metabolism. The review focuses on parenteral routes of administration targeting drug delivery either in a site-specific or systemic way. Osmotic pumps consist of three building blocks: osmotic agent, solvent, and drug. This is used to categorize pumps into (i) single compartment systems using water from body fluids as solvent and the drug itself as the osmotic agent, (ii) two compartment systems employing a separate osmotic agent, and (iii) multi-compartment architectures employing solvent, drug and osmotic agent separately. In parallel to the micropumps, relevant applications and therapies are discussed.


Developmental regulation of preproenkephalin mRNA in the ovine paraventricular nucleus: effects of stress and glucocorticoids.
The opioid peptides have profound effects at several levels within the hypothalamo-pituitary-adrenal (HPA) axis. Activation of fetal HPA function occurs during late gestation, and as part of the fetal adaptive response to stress. Changes in the relative levels, localization and distribution of hypothalamic preproenkephalin (PENK) mRNA in the ovine hypothalamic paraventricular nucleus (PVN) during development were examined by in situ hybridization histochemistry. The effects of fetal hypoxemia applied in the presence or absence of concomitant cortisol, to establish negative feedback potential in late gestation were also investigated. PENK mRNA was present at low levels within the PVN, by d60 (term d147). During mid to late gestation, there was an increase in PENK mRNA levels from d60-80 to d100-120, then reaching a peak at d130-140. Levels then decreased dramatically during the last 5-7 days prior to parturition, but increased again in the newborn lamb. Throughout gestation, PENK mRNA was confined exclusively to the parvocellular region of the PVN. Cortisol infusion induced significant decreases (P < 0.05) in PENK mRNA, in normoxemic fetuses at d135 of gestation. The hypoxemic insult, which is known to stimulate plasma ACTH and cortisol, in these fetuses, did not significantly affect PENK mRNA. There was no significant difference in hypoxemia significantly decreased PENK mRNA compared to the saline-infused normoxemic fetuses. Together, these results indicate that the elevation of endogenous fetal cortisol, that occurs at the end of gestation, may act to inhibit expression of the PENK gene in the hypothalamic PVN of the developing ovine fetus.


Medial gastrocnemius resection for calf reduction by using a popliteal mini-incisional approach in Asians.
To create a new approach of resecting medial gastrocnemius for calf reduction and to meet the increasing requirement of the beauty standard of calf sliming in Asian. Twenty patients with 39 calves underwent gastrocnemius resection for calf reduction. Under general anesthesia, a 5 cm incision, along the popliteal crease, was made down to the sub-popliteal deep fascia on a prone position. The medial belly of the gastrocnemius muscle was then dissected, in a blunt way, from the popliteal fossa down to the Achilles tendon around the muscular belly when its neurovascular bundle was ligated and cut off. Thereafter, the medial gastrocnemius was pulled out of the wound and incised transversely off at the level of the popliteal fossa while the attachment to the Achilles was transected with a long rectangular scissors. The incisional wound was finally closed in layers. Twenty patients with 39 calves were treated using the above-mentioned technique without severe complications. The harvested gastrocnemius muscle weighed 192.1 g in mean (from 104.5 g to 307.6 g). The calf circumference was significantly decreased from 36.3 cm in mean to 32.8 cm in mean before and after the operation (p <0.05). The above-mentioned technique may be a safer, simpler, and more efficient method for calf reduction with less morbidity of the potential complications, in comparison with the traditional techniques.


Assessment of Confabulation in Patients with Alcohol-Related Cognitive Disorders: The Nijmegen-Venray Confabulation List (NVCL-20).
Even though the first awareness of confabulations is often based on observations, only questionnaires and structured interviews quantifying provoked confabulations are available. So far, no tools have been developed to measure spontaneous confabulation. This study describes and validates an observation scale for quantifying confabulation behavior, including spontaneous confabulations, in clinical practice. An observation scale consisting of 20 items was developed, the Nijmegen-Venray Confabulation List-20 (NVCL-20). This scale covers spontaneous confabulation, provoked confabulation, and memory and orientation. Professional caregivers completed the NVCL-20 for 28 Korsakoff (KS) patients and 24 cognitively impaired chronic alcoholics (ALC). Their ratings were related to the Dalla Barba Confabulation Battery (DBCB), Provoked Confabulation Test (PCT), and standard neuropsychological tests. The categories of the NVCL-20 have "good" to "excellent" internal consistency and inter-rater agreement. The KS patients confabulated more (both spontaneously and provoked), and more memory and orientation problems were observed. Correlations with neuropsychological test scores showed that confabulations were associated with memory deficits, but not with intrusions or tests of executive dysfunction. The NVCL-20 is the first instrument that includes items addressing spontaneous confabulation. Administration is reliable, valid and feasible in clinical practice, making it a useful addition to existing confabulating measures.


Emotional blunting in patients with depression. Part I: clinical characteristics.
Emotional blunting-inability to feel positive or negative emotions, detachment, or reduced emotional responsiveness-is common in people with depression. However, there is a paucity of studies comprehensively investigating this symptom and its functional impact. This study investigated the experience of emotional blunting, and its impact on overall functioning and quality of life, in the acute and remission phases of depression from the perspective of patients and healthcare providers. This paper presents data on the clinical presentation of emotional blunting in depression from the patient perspective. Cross-sectional, observational study conducted in Brazil, Canada, and Spain between April 15 and May 18, 2021. Data were collected via a self-completed online survey. Respondents were adults with depression (acute or remission phase), who were currently using a prescribed antidepressant, and who reported emotional blunting during the past 6 weeks. Emotional blunting was assessed using the Oxford Depression Questionnaire (ODQ; total score range 26-130, higher scores indicate greater emotional blunting). In all, 752 patients completed the survey (62% female; mean age, 45 years). Overall, 44% of patients rated their emotional blunting as extremely severe (acute phase [n = 300], 72%; remission phase [n = 452], 25%; difference, p < 0.01). In all, 56% of patients considered their emotional blunting to be caused by their depression (acute phase, 62%; remission phase, 52%). Mean ODQ total score was 94.8 for patients in the acute phase of depression and 85.7 for those in remission (difference, p < 0.01). Mean score for the ODQ 'antidepressant as cause' domain (maximum possible score, 30) was 18.0 in patients in the acute phase and 17.6 in those in remission. Overall, 45% of patients believed that their antidepressant medication was blunting their emotions and 39% were considering stopping or had already stopped their antidepressant because of perceived emotion-related side effects. Almost three-quarters of patients in the acute phase of depression and one-quarter of those in remission reported severe emotional blunting. Approximately 56% of patients considered their emotional blunting to be caused by their depression, while 45% believed that their antidepressant medication was negatively affecting their emotions. Just over one-third of patients were considering stopping or had stopped their antidepressant as a result.


Urinary incontinence in 9-16 year olds with cystic fibrosis compared to other respiratory conditions and a normal group.
Individuals with cystic fibrosis (CF) are deemed at risk of developing urinary incontinence (UI) due to repeated coughing and other factors causing increased pressure on the pelvic floor. Increased incidence of UI is recognised in women and increasingly in men and children. However, there is little comparison with normal controls and other respiratory conditions with chronic cough. Our aim was to report the incidence, degree and impact of UI in 9-16 year olds related to clinical status in CF, compared to these. 9-16 year olds were invited to fill in a self-administered anonymous/confidential questionnaire at clinic. Data recorded were sex, age, height, weight, spirometry expressed as percentage predicted. Normal controls - age and sex only recorded. No significant differences were found between incidence of UI (21% CF; 22% respiratory; and 17% normal controls, P=0.43). No relationship found between respiratory or nutritional status and UI. Laughing, exercise and cough were the most common causes of UI. No difference between groups for age range, physiotherapy, breathlessness, antibiotics, urinary tract infections and menarche. Only 6% reported more than a few drops of UI. Incidence of urinary incontinence is no different between 9-16 year old girls and boys with CF, and controls.