Region-based wavelet coding methods for digital mammography.
Spatial resolution and contrast sensitivity requirements for some types of medical image techniques, including mammography, delay the implementation of new digital technologies, namely, computer-aided diagnosis, picture archiving and communications systems, or teleradiology. In order to reduce transmission time and storage cost, an efficient data-compression scheme to reduce digital data without significant degradation of medical image quality is needed. In this study, we have applied two region-based compression methods to digital mammograms. In both methods, after segmenting the breast region, a region-based discrete wavelet transform is applied, followed by an object-based extension of the set partitioning in hierarchical trees (OB-SPIHT) coding algorithm in one method, and an object-based extension of the set partitioned embedded block (OB-SPECK) coding algorithm in the other. We have compared these specific implementations against the original SPIHT and the new standard JPEG 2000, both using reversible and irreversible filters, on five digital mammograms compressed at rates ranging from 0.1 to 1.0 bit per pixel (bbp). Distortion was evaluated for all images and compression rates by the peak signal-to-noise ratio. For all images, OB-SPIHT and OB-SPECK performed substantially better than the traditional SPIHT and JPEG 2000, and a slight difference in performance was found between them. A comparison applying SPIHT and the standard JPEG 2000 to the same set of images with the background pixels fixed to zero was also carried out, obtaining similar implementation as region-based methods. For digital mammography, region-based compression methods represent an improvement in compression efficiency from full-image methods, also providing the possibility of encoding multiple regions of interest independently.


The best orbital and pair function for describing ionic and excited states on top of the exact ground state.
Many-body processes inevitably lead to the transition from one many-body wavefunction to another. Due to the complexity of the initial and final states many-body wavefunctions, one often wishes to try and describe such transitions using only a single-particle function. While there are numerous types of orbitals and densities which are commonly used, the question remains which one is optimal and in which sense. Here we present the optimal one and two body functions whose anti-symmetrized product with the initial state yields the maximal overlap with the final state. A definition of the above optimal condition and its rigorous proof are given. The resulting optimal functions shed additional light on the well-known Dyson orbital and reduced transition matrix, demonstrating further their physical meaning as independent functions.


[Embryonic and post-embryonic development of the parietal and visceral peritoneum in white mice].
Light and electron microscopy were used in order to investigate histogenesis of the parietal and visceral peritoneum of white mice in embryonic and postembryonic periods of development. Four periods were distinguished, during which gradual differentiation of the primordium material into tissue structures (mesothelium and the connective tissue) of the peritoneum were observed. Asynchronous differentiation of the mesothelium as well as certain correlation in the degree of differentiation of mesothelial and mesenchymal cells took place at all stages of the embryonic and postembryonic development. More differentiated cells of prolonged shape were predominant in the mesenchyma even at early stages (11 days) in those portions where the lining of the secondary cavity of the body resembled mesothelim in its structure.


The regulation of propionate oxidation in Prototheca zopfii.
1. Whole cell suspensions of Prototheca zopfii grown on propionate oxidize propionate, acrylate, malonic semialdehyde and acetate immediately, whereas acetate-grown cells only oxidize acrylate or propionate rapidly after a lag of 20-30min. This adaptation to propionate is slowed down by 8-azaguanine or p-fluorophenylalanine, and is not influenced by adding an ammonium salt or an amino acid mixture. 2. The adaptation involves induction of the enzymes of beta-oxidation of propionate. 3. A small proportion (5-8%) of the activities of propionyl-CoA dehydrogenase, beta-hydroxypropionate dehydrogenase and malonic semialdehyde dehydrogenase are consistently associated with mitochondria isolated from propionate-grown cells. 4. Such mitochondria will oxidize propionyl-CoA, beta-hydroxypropionate and malonic semialdehyde, and the respiration rates with these substrates in the presence of inorganic phosphate are ADP-dependent. 5. Mitochondria from acetate-grown cells do not contain detectable activities of the enzymes of propionate oxidation.


Prevention of postlaminectomy scar formation.
An animal experimental study was performed to investigate prevention of scar formation under lumbar laminectomy by using new biodegradable interposing materials-- polylactic acid (PLA) foam and membrane. The experimental animals consisted of 32 dogs, 16 control and 16 experimental. The experimental surgery consisted of L5 or L6 complete laminectomy and covering of the laminectomy defect with the experimental materials. The same procedure but without the covering of the laminectomy defect was performed on the control group animals. Animals were sacrificed at varying intervals (2-52 weeks) and the lumbar spines were evaluated with histologic preparations. The PLA membrane is found to be a promising material for prevention of scar tissue extension and adhesion after laminectomy but has a problem of marginal fitting. PLA foam is found to behave as a scaffold for scar tissue extension and adhesion onto the nerve. Other foamy materials such as gelatin foam or avitane are probably behaving similarly, causing scar tissue extension and adhesion. The new materials were found to be completely biocompatible and slowly biodegradable. A combined use of posteriorly convexed stiff PLA membrane and marginal gap filler with PLA foam may provide solutions for both prevention of scar tissue extension and adhesion and prevention of postlaminectomy spinal stenosis.


The role of KIR and HLA interactions in pregnancy complications.
Combinations of KIR and HLA genes associate with pregnancy complications as well as with many other clinical scenarios. Understanding how certain KIR and HLA genes influence the biology of a disease is, however, a formidable challenge. These are the two most variable gene families in the human genome. Moreover, the biology of a disease is best understood by studying the cells of the affected tissue. Natural Killer (NK) cells express KIR and are the most abundant leukocytes in the uterus. Most of our knowledge of NK cells is based on what we have learned from cells isolated from blood, but these are different from their tissue resident counterparts, including uterine NK (uNK) cells. Reproductive immunology faces an additional challenge: Two genotypes must be considered because both maternal and foetal HLA class I molecules may influence the outcome of pregnancy, most likely through interactions with maternal KIR expressed on uNK cells. Maternal uNK cells are not spontaneously cytotoxic and instead engage in interactions with trophoblast. We hypothesise that these interactions regulate allocation of resources between the foetus and the mother and may go wrong in diseases of pregnancy.


Prevention of left ventricular remodeling with granulocyte colony-stimulating factor after acute myocardial infarction: final 1-year results of the Front-Integrated Revascularization and Stem Cell Liberation in Evolving Acute Myocardial Infarction by Granulocyte Colony-Stimulating Factor (FIRSTLINE-AMI) Trial.
Experimental and clinical evidence has recently shown that pluripotent stem cells can be mobilized by granulocyte colony-stimulating factor (G-CSF) and may enhance myocardial regeneration early after primary percutaneous coronary intervention (PCI) management of acute myocardial infarction. Sustained or long-term effects of mobilized CD34-positive mononuclear stem cells, however, are unknown. Thirty consecutive patients with ST-elevation myocardial infarction undergoing primary PCI with stenting and abciximab were selected for the study 85+/-30 minutes after PCI; 15 patients were randomly assigned to receive subcutaneous G-CSF at 10 microg/kg body weight for 6 days in addition to standard care including aspirin, clopidogrel, an angiotensin-converting enzyme inhibitor, beta-blocking agents, and statins. In patients with comparable demographics and clinical and infarct-related characteristics, G-CSF stimulation led to sustained mobilization of CD34 positive mononuclear cells (MNC(CD34+)), with a 20-fold increase (from 3+/-2 at baseline to 66+/-54 MNC(CD34+)/microL on day 6; P<0.001); there was no evidence of leukocytoclastic effects, accelerated restenosis rate, or any late adverse events. Within 4 months, G-CSF-induced MNC(CD34+) mobilization led to enhanced resting wall thickening in the infarct zone of 1.16+/-0.29 mm (P<0.05 versus control), which was sustained at 1.20+/-0.28 after 12 months (P<0.001 versus control). Similarly, left ventricular ejection fraction improved from 48+/-4% at baseline to 54+/-8% at 4 months (P<0.005 versus control) and 56+/-9% at 12 months (P<0.003 versus control and paralleled by sustained improvement of wall-motion score index from 1.70+/-0.22 to 1.42+/-0.26 and 1.33+/-0.21 at 4 and 12 months, respectively), after G-CSF (P<0.05 versus baseline and P<0.03 versus controls). Accordingly, left ventricular end-diastolic diameter showed no remodeling and stable left ventricular dimensions after G-CSF stimulation, whereas left ventricular end-diastolic diameter in controls revealed enlargement from 55+/-4 mm at baseline to 58+/-4 mm (P<0.05 versus baseline) at 12 months after infarction and no improvement in diastolic function. Mobilization of MNC(CD34+) by G-CSF after primary PCI may offer a pragmatic strategy for improvement in ventricular function and prevention of left ventricular remodeling 1 year after acute myocardial infarction.


[Effectiveness evaluation and prognostic factor analysis in patients with minor salivary gland carcinoma of the hard palate].
Minor salivary gland carcinoma of the hard palate is rare, and its long-term survival rate is high, making it difficult to evaluate the prognostic factors and the efficacy of treatment. This study was designed to evaluate the efficacy of treatment and investigate the prognostic factors of minor salivary gland carcinoma of the hard palate. Ninety-six cases of minor salivary gland carcinoma of the hard palate hospitalized in Cancer Center, Sun Yat-sen University, from 1964 to 2001 were reviewed retrospectively. The cumulative survival rate was analyzed by Kaplan-Meier method. The factors were compared using the log-rank test. The influencing factors were screened by Cox proportional hazards model. The 5- and 10-year overall survival rates were 65.60% and 47.90%, respectively. The 5- and 10-year disease-specific survival rates for the patients treated with surgery (53 cases) and surgery + radiotherapy (35 cases) were 73.14%, 67.40% and 66.58%,46.60%,respectively. Multivariate analysis showed that age >or=50 years old,tumor size >or=3 cm,surgical margin status,and recurrence were independently associated with decreased survival rates (P< 0.05). Surgery or surgery dominated multi-modality therapy was the principal treatment modality for minor salivary gland carcinoma of the hard palate. Age >or=50 years old, tumor size >or=3 cm, surgical margin status, and recurrence are independent factors affecting the prognosis.


Appropriate Implantable Cardioverter-Defibrillator Therapy in Patients with Ventricular Arrhythmia of Unclear Cause in Secondary Prevention of Sudden Cardiac Death.
In this study, we sought to investigate the occurrence of appropriate implantable cardioverter-defibrillator (ICD) therapies and inappropriate shocks in secondary prevention ICD recipients with ventricular arrhythmia of unclear cause and ventricular arrhythmia in the context of underlying heart disease. In this retrospective study, consecutive patients with an ICD implanted for secondary prevention in the University Medical Center Groningen (UMCG), the Netherlands between 1 January 2012 and 31 December 2018 were included. Patients were classified as having ventricular arrhythmia of unclear cause if no clear cause was found which could explain the index ventricular arrhythmia. The primary outcome was appropriate ICD therapy. The study population consisted of 257 patients. In 220 patients, an underlying heart disease could be identified as the cause of ventricular arrhythmia, while 37 patients had an unclear cause of ventricular arrhythmia. The median age was 64 years (interquartile range (IQR) 53-72 years). Forty-five (18%) patients were women. During a median duration of follow-up of 6.2 years (IQR 4.8-7.8 years), appropriate ICD therapy occurred in 95 (37%) patients. This number was 90 (41%) in the group with a clear etiology and 5 (14%) in the group with an unclear etiology. In multivariable analysis, index ventricular arrhythmia of unclear cause was associated with fewer appropriate ICD therapies (HR 0.37 [95% CI 0.14-0.99]; p = 0.048), as well as an increased risk of inappropriate ICD shocks (HR 3.71 [95% CI 1.17-11.80]; p = 0.026). Index ventricular arrhythmia of unclear cause was significantly associated with fewer appropriate ICD therapies.


Physical Management of Scar Tissue: A Systematic Review and Meta-Analysis.
Objective: The aim of this systematic review with meta-analysis was to describe the status on the effects of physical scar treatments on pain, pigmentation, pliability, pruritus, scar thickening, and surface area. Design: Systematic review and meta-analysis. Subjects: Adults with any kind of scar tissue. Interventions: Physical scar management versus control or no scar management. Outcome measures: Pain, pigmentation, pliability, pruritus, surface area, scar thickness. Results: The overall results revealed that physical scar management is beneficial compared with the control treatment regarding the management of pain (p = 0.012), pruritus (p < 0.001), pigmentation (p = 0.010), pliability (p < 0.001), surface area (p < 0.001), and thickness (p = 0.022) of scar tissue in adults. The observed risk of bias was high for blinding of participants and personnel (47%) and low for other bias (100%). Conclusions: Physical scar management demonstrates moderate-to-strong effects on improvement of scar issues as related to signs and symptoms. These results show the importance of specific physical management of scar tissue.


Genetic divergence among sweet corn lines estimated by microsatellite markers.
The purpose of this study was to analyze the genetic diversity of 15 sugary-1 sweet corn lines by microsatellite markers. One hundred pairs of simple sequence repeat primers that were mapped for field corn were tested. Of these primers, 15% were polymorphic, and all were selected for the evaluation. These primers identified a total of 39 alleles among the 15 loci that were evaluated. The number of alleles per locus in the genotypes ranged from 2 to 4, with an average of 2.60 alleles per locus; the highest number of alleles was observed at the loci Bnlg1083, Umc1241, and Umc1590. The occurrence of null alleles at locus Umc1363 was evident only in line DN44. The proportion of polymorphic loci was the highest in lines DN17.1 and DN6 (73.33%), whereas lines DN47, DN23, and DN28 were more monomorphic than other lines. The loci Bnlg1083 and Umc1506 were polymorphic in 8 and 7 lines, respectively, indicating that these loci might be effective and promising for the identification of polymorphism in other sweet corn lines. The genetic diversity calculated by Rogers' genetic distances indicated the lowest genetic similarity between lines DN9 and DN28 (0.7603) and the highest similarity between lines DN19 and DN6 (0.3724). The dendrogram obtained by the unweighted pair-group method based on arithmetic averages indicated the formation of 4 major groups, showing the crossing of the genotypes DN19 and DN6 with DN8 as a possible alternative for the expression of heterozygosis.


[Sex-specific differences in drug treatment].
Following the disastrous experience with thalidomide women were largely excluded from clinical trials. A change in this paradigm can be observed most recently. For the pharmacokinetics and -dynamics of drugs a body of evidence does exist to prove the presence of significant sex-related differences. Especially fort he major drug metabolizing enzymes, the cytochrome P 450 family, but also for phase II reactions such as glucuronidation, sex-differences were observed. However, most of these differences are either clinically not relevant or were not just observed, because they result in slight increases in the frequency of adverse reactions. Major sex-specific differences were observed for the cardiac elektrophysiology, for opiate and benzodiazepine receptors. Women are significantly more likely to experience drug-induced QT-prolongation and torsade-de-pointes arrhythmia. It should also be considered that conditions such as depression, myocardial infarction and heart failure are characterized by gender-specific symptoms and therefore may deserve a gender-specific therapy. Different trials and epidemiological surveys have repeatedly shown that women experience more adverse drug effects than men.


Origin of estrogen in a postmenopausal woman with a nonendocrine tumor of the ovary and endometrial hyperplasia.
The origin and quantity of estrogen and androgen were measured in a postmenopausal woman with clinical signs of estrogen excess and a nonendocrine tumor of the ovary. The plasma androstenedione production rate was elevated 5-fold. The estrone production rate was also five times that normally expected for a postmenopausal women and could be accounted for totally by the extraglandular conversion of plasma and androstenedione. Following removal of the tumor, the concentration of plasma androstenedione and the estrone production rate fell dramatically to normal postmenopausal levels. It is concluded that this markedly increased androstenedione production was the result of excessive secretion of androstenedione by the hyperplastic stromal cells of the ovary containing the mucinous cystadenocarcinoma. The excessive prehormone production together with its normal extraglandular conversion to estrone resulted in the massive increase in endogenous estrogen formation.


Coronary arterial fistulas.
A coronary arterial fistula is a connection between one or more of the coronary arteries and a cardiac chamber or great vessel. This is a rare defect and usually occurs in isolation. Its exact incidence is unknown. The majority of these fistulas are congenital in origin although they may occasionally be detected after cardiac surgery. They do not usually cause symptoms or complications in the first two decades, especially when small. After this age, the frequency of both symptoms and complications increases. Complications include 'steal' from the adjacent myocardium, thrombosis and embolism, cardiac failure, atrial fibrillation, rupture, endocarditis/endarteritis and arrhythmias. Thrombosis within the fistula is rare but may cause acute myocardial infarction, paroxysmal atrial fibrillation and ventricular arrhythmias. Spontaneous rupture of the aneurysmal fistula causing haemopericardium has also been reported. The main differential diagnosis is patent arterial duct, although other congenital arteriovenous shunts need to be excluded. Whilst two-dimensional echocardiography helps to differentiate between the different shunts, coronary angiography is the main diagnostic tool for the delineation of the anatomy. Surgery was the traditional method of treatment but nowadays catheter closure is recommended using a variety of closure devices, such as coils, or other devices. With the catheter technique, the results are excellent with infrequent complications.


[Isolation of novel expression sequences of C2H2 type zinc finger protein gene from human brain tissue according to the conservation of zinc finger motif].
By low stringency PCR amplification of genomic DNA using the primers designed based on the conservation of zinc finger motif, we got 8 gradient eletrophoretic bands. After recovery of the second and third bands, the DNA fragments in them were cloned and sequenced. Compared to the GenBank database, among these 60 segments containing zinc finger motif, 23 segments were novel zinc finger genes' genomic segments. Then the human brain tissue cDNA library was screened, using these segments as probes, and 44 positive clones were obtained. Rescreening 28 of them, we got 20 rescreened clones. All of them were sequenced and sent to the GenBank DNA database for sequence analysis, the results showed that 16 were novel C2H2 type zinc finger protein cDNA segments. The cDNA segments encoding the novel C2H2 type zinc finger proteins provide the basic materials for cloning of full length cDNA of valuable novel zinc finger protein genes.


Large-Scale Screening for Monogenic and Clinically Defined Familial Hypercholesterolemia in Iceland.
Objective: Familial hypercholesterolemia (FH) is traditionally defined as a monogenic disease characterized by severely elevated LDL-C (low-density lipoprotein cholesterol) levels. In practice, FH is commonly a clinical diagnosis without confirmation of a causative mutation. In this study, we sought to characterize and compare monogenic and clinically defined FH in a large sample of Icelanders. Approach and Results: We whole-genome sequenced 49 962 Icelanders and imputed the identified variants into an overall sample of 166 281 chip-genotyped Icelanders. We identified 20 FH mutations in LDLR, APOB, and PCSK9 with combined prevalence of 1 in 836. Monogenic FH was associated with severely elevated LDL-C levels and increased risk of premature coronary disease, aortic valve stenosis, and high burden of coronary atherosclerosis. We used a modified version of the Dutch Lipid Clinic Network criteria to screen for the clinical FH phenotype among living adult participants (N=79 058). Clinical FH was found in 2.2% of participants, of whom only 5.2% had monogenic FH. Mutation-negative clinical FH has a strong polygenic basis. Both individuals with monogenic FH and individuals with mutation-negative clinical FH were markedly undertreated with cholesterol-lowering medications and only a minority attained an LDL-C target of <2.6 mmol/L (<100 mg/dL; 11.0% and 24.9%, respectively) or <1.8 mmol/L (<70 mg/dL; 0.0% and 5.2%, respectively), as recommended for primary prevention by European Society of Cardiology/European Atherosclerosis Society cholesterol guidelines. Conclusions: Clinically defined FH is a relatively common phenotype that is explained by monogenic FH in only a minority of cases. Both monogenic and clinical FH confer high cardiovascular risk but are markedly undertreated.


[To evaluate the role of OLT on splenomegaly of portal hypertension by the radiological changes of splenic morphology and collaterals].
To explore the effect of orthotopic liver transplantation (OLT) on portal hypertension by observing the radiological changes of splenic volume and collaterals before and after OLT. In our hospital 56 patients performing OLT due to cirrhosis, portal hypertension and splenomegaly were classified into five groups according to their following-up time: A (≤3 months), B (>3-6 months), C (>6-12 months), D (>12-24 months), and E (>24 months). Twenty health people were chose as control group (F). The splenic width, thickness, length, volume, diameter of portal and splenic vein and collaterals were measured and observed in every patient of six groups before and after OLT respectively. After OLT, the splenic volume decreased by 25.4%, 27.8%, 21.9%, 25.2%, 27.7% in five groups respectively, which was still larger than the normal group (P<0.05). Gastroesophageal varices in 31 cases (81.6%, 31/36) became normal after OLT. The opened umbilical vein disappeared and the retroperitoneal varices persisted in five cases after OLT. Splenomegaly and opened collaterals can be relieved by OLT effectively. The splenic volume didn't change obviously until it decreased by 25% in the three months after OLT. Gastroesophageal varices can be removed in most of patients after OLT. The splenomegaly could last paralled with the splenic vein and retroperitoneal varices after OLT. After OLT, correct disposal of splenic and collateral changes could improve the success rate and the long-term treatment effect of OLT.


An unexpected encounter with jejunal web after foreign bodies entrapment in a toddler.
We present a very rare case of jejunal web discovered after a toddler presented with foreign bodies entrapment, following incidental ingestion. This is perhaps the first case reported in the English publication. Expectant management with spontaneous passage of foreign bodies failed. Serial abdominal radiographs failed to determine the site of the foreign bodies accurately. Endoscopic removal was unsuccessful. Surgical removal was warranted with unexpected intra-operative finding of a jejunal web with foreign body entrapment. Although rare, a congenital intestinal web must be considered in a child presents with failure of expectant management following foreign body ingestion as surgical intervention is necessary.


Selective modulation of CD4+ T cells from lupus patients by a promiscuous, protective peptide analog.
A peptide encompassing residues 131-151 of the spliceosomal U1-70K protein and its analog phosphorylated at Ser140 were synthesized as potential candidates for the treatment of patients with lupus. Studies in the MRL/lpr and (NZB x NZW)F1 lupus models have demonstrated that these sequences contain a CD4+ T cell epitope but administration of the phosphorylated peptide only ameliorates the clinical manifestations of treated MRL/lpr mice. Binding assays with soluble HLA class II molecules and molecular modeling experiments indicate that both peptides behave as promiscuous epitopes and bind to a large panel of human DR molecules. In contrast to normal T cells and T cells from non-lupus autoimmune patients, we found that PBMCs from 40% of lupus patients selected randomly and CFSE-labeled CD4+ T cells proliferate in response to peptide 131-151. Remarkably, however, we observed that phosphorylation of Ser140 prevents CD4+ T cells proliferation but not secretion of regulatory cytokines, suggesting a striking immunomodulatory effect of phosphorylated analog on lupus CD4+ T cells that was unique to patients. The analog might act as an activator of regulatory T cells or as a partial agonist of TCR.


Gecko-inspired surfaces: a path to strong and reversible dry adhesives.
The amazing adhesion of gecko pads to almost any kind of surfaces has inspired a very active research direction over the last decade: the investigation of how geckos achieve this feat and how this knowledge can be turned into new strategies to reversibly join surfaces. This article reviews the fabrication approaches used so far for the creation of micro- and nanostructured fibrillar surfaces with adhesive properties. In the light of the pertinent contact mechanics, the adhesive properties are presented and discussed. The decisive design parameters are fiber radius and aspect ratio, tilt angle, hierarchical arrangement and the effect of the backing layer. Also first responsive systems that allow thermal switching between nonadhesive and adhesive states are described. These structures show a high potential of application, providing the remaining issues of robustness, reliability, and large-area manufacture can be solved.


High-throughput estimation of incident light, light interception and radiation-use efficiency of thousands of plants in a phenotyping platform.
Light interception and radiation-use efficiency (RUE) are essential components of plant performance. Their genetic dissections require novel high-throughput phenotyping methods. We have developed a suite of methods to evaluate the spatial distribution of incident light, as experienced by hundreds of plants in a glasshouse, by simulating sunbeam trajectories through glasshouse structures every day of the year; the amount of light intercepted by maize (Zea mays) plants via a functional-structural model using three-dimensional (3D) reconstructions of each plant placed in a virtual scene reproducing the canopy in the glasshouse; and RUE, as the ratio of plant biomass to intercepted light. The spatial variation of direct and diffuse incident light in the glasshouse (up to 24%) was correctly predicted at the single-plant scale. Light interception largely varied between maize lines that differed in leaf angles (nearly stable between experiments) and area (highly variable between experiments). Estimated RUEs varied between maize lines, but were similar in two experiments with contrasting incident light. They closely correlated with measured gas exchanges. The methods proposed here identified reproducible traits that might be used in further field studies, thereby opening up the way for large-scale genetic analyses of the components of plant performance.


Under the mirror of the sleeping water: Poussin's Narcissus.
Examined in conjunction with a close reading of Ovid's Metamorphoses, Nicolas Poussin's four paintings on the preoccupying theme of Narcissus and Echo reflect a developing aesthetic interpretation of its textual source. Poussin's reflective vision supports a radical reappraisal of the enigmatic myth at the heart of psychoanalytic theory and practice, in which Narcissus is construed as a far more object-related figure that seeks the formative, affirmative mirroring of the other. This in turn encourages a more versatile conceptualization of narcissistic disturbance, in which an etiologically heterogenous constellation of issues stems from a variety of disturbances in the myriad dynamic and developmental aspects of mirroring and attunement: the narcissisms.


7-Chloro-5-cyclo-propyl-9-methyl-5H-4,5,6,10-tetra-aza-dibenzo[a,d]cyclo-hepten-11(10H)-one.
In the title compound, C(15)H(13)ClN(4)O, which is a chloro derivative of the drug Nevirapine, the diazepine ring is in a twisted boat conformation. The pyridine rings fused to the diazepine fragment form a dihedral angle of 58.44 (10)° and the mol-ecule adopts a butterfly shape. The mol-ecules are joined via N-H⋯N hydrogen bonding into polymeric chains down the b axis. All weaker C-H⋯O inter-actions involve the carbonyl O atom as acceptor.


Activity of selected enzymes in arterial wall and blood serum of rats with experimental atherosclerosis.
The activity of lysosomal hydrolases (hyaluronidase and beta-glucuronidase) as well as elastolytic activity in arterial wall and blood serum of rats with experimental atherosclerosis were determined. An increase of the enzyme activity was found in arterial wall, while in blood serum the rise of lysosomal hydrolase activity was accompanied by and unchanged level of elastolytic activity, as compared to control animals. The present studies show the participation of lysosomal enzymes and elastolytic activity in the development of atherosclerotic changes.


A single exposure to the tremorgenic mycotoxin lolitrem B inhibits voluntary motor activity and spatial orientation but not spatial learning or memory in mice.
The indole diterpenoid toxin lolitrem B is a tremorgenic agent found in the common grass species, perennial ryegrass (Lolium perenne). The toxin is produced by a symbiotic fungus Epichloë festucae (var. lolii) and ingestion of infested grass with sufficient toxin levels causes a movement disorder in grazing herbivores known as 'ryegrass staggers'. Beside ataxia, lolitrem B intoxicated animals frequently show indicators of cognitive dysfunction or exhibition of erratic and unpredictable behaviours during handling. Evidence from field cases in livestock and controlled feeding studies in horses have indicated that intoxication with lolitrem B may affect higher cortical or subcortical functioning. In order to define the role of lolitrem B in voluntary motor control, spatial learning and memory under controlled conditions, mice were exposed to a known dose of purified lolitrem B toxin and tremor, coordination, voluntary motor activity and spatial learning and memory assessed. Motor activity, coordination and spatial memory were compared to tremor intensity using a novel quantitative piezo-electronic tremor analysis. Peak tremor was observed as frequencies between 15 and 25Hz compared to normal movement at approximately 1.4-10Hz. A single exposure to a known tremorgenic dose of lolitrem B (2 mg/kg IP) induced measureable tremor for up to 72 h in some animals. Initially, intoxication with lolitrem B significantly decreased voluntary movement. By 25 h post exposure a return to normal voluntary movement was observed in this group, despite continuing evidence of tremor. This effect was not observed in animals exposed to the short-acting tremorgenic toxin paxilline. Lolitrem B intoxicated mice demonstrated a random search pattern and delayed latency to escape a 3 h post intoxication, however by 27 h post exposure latency to escape matched controls and mice had returned to normal searching behavior indicating normal spatial learning and memory. Together these data indicate that the tremor exhibited by lolitrem B intoxicated mice does not directly impair spatial learning and memory but that exposure does reduce voluntary motor activity in intoxicated animals. Management of acutely affected livestock suffering toxicosis should be considered in the context of their ability to spatially orientate with severe toxicity.


Relationship between Inter-Eye Asymmetries in Corneal Hysteresis and Visual Field Severity in Patients with Primary Open-Angle Glaucoma.
This study investigated the influence of asymmetric corneal hysteresis (CH) on asymmetric visual field impairment between right and left eyes in patients with primary open-angle glaucoma (POAG) without a history of intraocular surgery. CH, corneal resistance factor (CRF), and corneal compensated intraocular pressure (IOPcc) were measured using the Ocular Response Analyzer. Differences between the eyes (right eye-left eye: DIFRL) and CH-based and in target parameters (higher CH eye-lower CH eye: DIFCH) were calculated in the same patient. In 242 phakic eyes of 121 patients, older age (p < 0.001), lower CH (p = 0.001), and lower CRF (p = 0.007) were significantly associated with worse standard automated perimetry (SAP) 24-2 mean deviation (MD). The DIFsRL in axial length (p = 0.003), IOPcc (p = 0.028), and CH (p = 0.001) were significantly associated with the DIFRL in SAP24-2 MD, but not in central corneal thickness (CCT), Goldmann applanation tonometry (GAT) measurement, and CRF. When dividing the patients into two groups based on the median of the CH DIFsCH (0.46), the DIFsCH in CRF (p < 0.001), IOPcc (p < 0.001), CCT (p = 0.004), SAP24-2 MD (p < 0.001), and SAP10-2 MD (p = 0.010) were significantly different between the groups. Large inter-eye asymmetry in CH is an important explanatory factor for disease worsening in patients with POAG.


Outbreaks of contagious ecthyma in camels (Camelus dromedarius) in the Turkana district of Kenya.
Mortality among camel calves (Camelus dromedarius) is one of the most serious problems faced by camel herdsmen and, although there are several reasons for this mortality, diseases play a major role. In an investigation of outbreaks of contagious ecthyma in camels in the Turkana district of Kenya, four outbreaks were detected involving only camel calves. The principal lesions were distinct or largely coalesced pustules on the mouth, nose and muzzle. Direct electron microscopy of infected scabs was used to confirm the presence of the virus. Secondary infection of the pustules was common in affected calves. Morbidity in affected herds was 100%, with no adult involvement. Affected calves were unable to suckle properly. In all outbreaks, there was a concurrent outbreak of contagious pustular dermatitis in goat kids in the same household. Contagious ecthyma is an important disease in camels, contributing to calf debility and eventually to high calf mortality.


Diffusion in a generalized Rubinstein-Duke model of electrophoresis with kinematic disorder.
Using a generalized Rubinstein-Duke model, we prove rigorously that kinematic disorder leaves the prediction of the standard reptation theory for the scaling of the diffusion constant in the limit for long polymer chains D proportional to L(-2) unaffected. Based on an analytical calculation as well as on Monte Carlo simulations, we predict kinematic disorder to affect the center-of-mass diffusion constant of an entangled polymer in the limit for long chains by the same factor as single particle diffusion in a random barrier model.


An introduction to clinical negligence: nurses and the law.
Clinical negligence is a serious problem in the NHS, with claims and costs rising steadily. In order to understand the system fully, reference must be made to the increasingly complex and developing NHS quality regulation and management structure and the law must be considered in this context. This series of articles will look at the concept of clinical negligence and examine some of the legal issues that arise.


Multicomponent synthesis of chiral bidentate unsymmetrical unsaturated N-heterocyclic carbenes: copper-catalyzed asymmetric C-C bond formation.
A multicomponent strategy was applied to the synthesis of chiral bidentate unsaturated hydroxyalkyl- and carboxyalkyl-N-heterocyclic carbene (NHC) precursors. The newly developed low-cost chiral ligands derived from amino alcohols and amino acids were evaluated in copper-catalyzed asymmetric conjugated addition and asymmetric allylic alkylation, which afforded the desired tertiary and quaternary carbon stereocenters with excellent regio- and enantioselectivities (up to 99:1 e.r.).


A cell-free expression and purification process for rapid production of protein biologics.
Cell-free protein synthesis has emerged as a powerful technology for rapid and efficient protein production. Cell-free methods are also amenable to automation and such systems have been extensively used for high-throughput protein production and screening; however, current fluidic systems are not adequate for manufacturing protein biopharmaceuticals. In this work, we report on the initial development of a fluidic process for rapid end-to-end production of recombinant protein biologics. This process incorporates a bioreactor module that can be used with eukaryotic or prokaryotic lysates that are programmed for combined transcription/translation of an engineered DNA template encoding for specific protein targets. Purification of the cell-free expressed product occurs through a series of protein separation modules that are configurable for process-specific isolation of different proteins. Using this approach, we demonstrate production of two bioactive human protein therapeutics, erythropoietin and granulocyte-macrophage colony-stimulating factor, in yeast and bacterial extracts, respectively, each within 24 hours. This process is flexible, scalable and amenable to automation for rapid production at the point-of-need of proteins with significant pharmaceutical, medical, or biotechnological value.


Proposal of Modified Lung-RADS in Assessing Pulmonary Nodules of Patients with Previous Malignancies: A Primary Study.
In addition to the diameters of pulmonary nodules, the number and morphology of blood vessels in pure ground-glass nodules (pGGNs) were closely related to the occurrence of lung cancer. Moreover, the benign and malignant signs of nodules were also valuable for the identification of nodules. Based on these two points, we tried to revise Lung-RADS 2022 and proposed our Modified Lung-RADS. The aim of the study was to verify the diagnostic performance of Modified Lung-RADS for pulmonary solid nodules (SNs) and pure ground-glass nodules (pGGNs) in patients with previous malignancies. The chest CT and clinical data of patients with prior cancer who underwent pulmonary nodulectomies from 1 January 2018 to 30 November 2021 were enrolled according to inclusion and exclusion criteria. A total of 240 patients with 293 pulmonary nodules were included in this study. In contrast with the original version, the risk classification of pGGNs based on the GGN-vascular relationships (GVRs), and the SNs without burrs and with benign signs, could be downgraded to category 2. The sensitivity, specificity, and agreement rate of the original Lung-RADS 2022 and Modified Lung-RADS for pGGNs and SNs were calculated and compared. Compared with the original version, the sensitivity and agreement rate of the Modified version for pGGNs increased from 0 and 23.33% to 97.10% and 92.22%, respectively, while the specificity decreased from 100% to 76.19%. As regards SNs, the specificity and agreement rate of the Modified version increased from 44.44% to 75.00% (p < 0.05) and 88.67% to 94.09% (p = 0.052), respectively, while the sensitivity was unchanged (98.20%). In general, the diagnostic efficiency of Modified Lung-RADS was superior to that of the original version, and Modified Lung-RADS could be a preliminary attempt to improve Lung-RADS 2022.


Helicobacter pylori infection is associated with oxidatively damaged DNA in human leukocytes and decreased level of urinary 8-oxo-7,8-dihydroguanine.
Helicobacter pylori infection is responsible for inflammation, increased production of reactive oxygen species and oxidatively damaged DNA in the gastric mucosa. There is also evidence which suggests that H.pylori infection may lead to the development of several extragastroduodenal pathologies with reactive oxygen species involvement. In order to assess whether the infection may impose oxidatively damaged DNA not only in the target organ (stomach) but in other organs as well we decided, for the first time, to analyse the two kinds of oxidatively damaged DNA biomarkers: urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanine (8-oxoGua) as well as the level of oxidatively damaged DNA in leukocytes. Using high performance liquid chromatography prepurification/gas chromatography with isotope dilution mass detection methodology, we examined the amount of oxidatively damaged DNA products excreted into urine and the amount of 8-oxodG in the DNA of leukocytes' (with the the HPLC/EC technique) in three groups of children: (i) control group, (ii) H.pylori infected children and (iii) children with gastritis where H.pylori infection was excluded. The levels of 8-oxodG in DNA isolated from leukocytes of H.pylori infected patients and in the group with gastritis without H.pylori infection were significantly higher than in DNA isolated from the control group. The mean level of 8-oxoGua in urine samples of children infected with H.pylori was significantly lower than in the urine of the group with gastritis without H.pylori infection. The data suggest that inflammation itself, not just H.pylori infection, is responsible for the observed rise of 8-oxodG level in leukocytes. However, the observed decrease in the level of modified base in urine seems to be specific for H.pylori infection and possibly linked with nitric oxide mediated inhibition of a key base excision repair enzyme (human 8-oxo-7, 8-dihydroguanine glycosylase) responsible for the repair of 8-oxo-7,8-dihydroguanine.


bFGF Promotes Migration and Induces Cancer-Associated Fibroblast Differentiation of Mouse Bone Mesenchymal Stem Cells to Promote Tumor Growth.
Tumors recruit bone mesenchymal stem cells (BMSCs) to localize to tumor sites, which induces their conversion into cancer-associated fibroblasts (CAFs) that facilitate tumor progression. However, this process is poorly understood on the molecular level. In this study, we found that 4T1 breast cancer cells promoted the migration of BMSCs, and bFGF neutralizing antibody inhibited the migration of BMSCs induced by a tumor-conditioned medium. In addition, exogenous bFGF enhanced the migration of BMSCs in a dose-dependent manner in vitro. Furthermore, BMSCs promoted the proliferation of 4T1 tumor cells under BMSC-conditioned medium and in tumor xenograft model. Dramatically, BMSCs expressed CAF markers and produced collagen in the tumor microenvironment, and this transition was blocked by bFGF antibody. In addition, exogenous bFGF induced CAF differentiation of BMSCs. And bFGF increased phosphorylation of Erk1/2 and Smad3 in BMSCs and Erk inhibitor PD98059 was shown to block bFGF-induced Erk and Smad3 phosphorylation, suggesting that Erk/Smad3 signaling pathway involved in BMSC transdifferentiation induced by bFGF. Collectively, our results indicate that bFGF signaling plays indispensable roles in BMSC recruitment and transdifferentiation into CAFs and the consequent protumor effects, and targeting tumor stroma through bFGF inhibition maybe a promising strategy to suppress tumor progression.


Adenosine production by brain cells.
The early release of adenosine following traumatic brain injury (TBI) suppresses seizures and brain inflammation; thus, it is important to elucidate the cellular sources of adenosine following injurious stimuli triggered by TBI so that therapeutics for enhancing the early adenosine-release response can be optimized. Using mass spectrometry with 13 C-labeled standards, we investigated in cultured rat neurons, astrocytes, and microglia the effects of oxygen-glucose deprivation (OGD; models energy failure), H2 O2 (produces oxidative stress), and glutamate (induces excitotoxicity) on intracellular and extracellular levels of 5'-AMP (adenosine precursor), adenosine, and inosine and hypoxanthine (adenosine metabolites). In neurons, OGD triggered increases in intracellular 5'-AMP (2.8-fold), adenosine (2.6-fold), inosine (2.2-fold), and hypoxanthine (5.3-fold) and extracellular 5'-AMP (2.2-fold), adenosine (2.4-fold), and hypoxanthine (2.5-fold). In neurons, H2 O2 did not affect intracellular or extracellular purines; yet, glutamate increased intracellular adenosine, inosine, and hypoxanthine (1.7-fold, 1.7-fold, and 1.6-fold, respectively) and extracellular adenosine, inosine, and hypoxanthine (2.9-fold, 2.1-fold, and 1.6-fold, respectively). In astrocytes, neither H2 O2 nor glutamate affected intracellular or extracellular purines, and OGD only slightly increased intracellular and extracellular hypoxanthine. Microglia were unresponsive to OGD and glutamate, but were remarkably responsive to H2 O2 , which increased intracellular 5'-AMP (1.6-fold), adenosine (1.6-fold), inosine (2.1-fold), and hypoxanthine (1.6-fold) and extracellular 5'-AMP (5.9-fold), adenosine (4.0-fold), inosine (4.3-fold), and hypoxanthine (1.9-fold). Under these particular experimental conditions, cultured neurons are the main contributors to adenosine production/release in response to OGD and glutamate, whereas cultured microglia are the main contributors upon oxidative stress. Developing therapeutics that recruit astrocytes to produce/release adenosine could have beneficial effects in TBI.


Highly selective and sensitive phosphate anion sensors based on AlGaN/GaN high electron mobility transistors functionalized by ion imprinted polymer.
A novel ion-imprinted electrochemical sensor based on AlGaN/GaN high electron mobility transistors (HEMTs) was developed to detect trace amounts of phosphate anion. This sensor combined the advantages of the ion sensitivity of AlGaN/GaN HEMTs and specific recognition of ion imprinted polymers. The current response showed that the fabricated sensor is highly sensitive and selective to phosphate anions. The current change exhibited approximate linear dependence for phosphate concentration from 0.02 mg L(-1) to 2 mg L(-1), the sensitivity and detection limit of the sensor is 3.191 μA/mg L(-1) and 1.97 μg L(-1), respectively. The results indicated that this AlGaN/GaN HEMT-based electrochemical sensor has the potential applications on phosphate anion detection.


Upregulation of miR-496 Rescues Propofol-induced Neurotoxicity by Targeting Rho Associated Coiled-coil Containing Protein Kinase 2 (ROCK2) in Prefrontal Cortical Neurons.
Early exposure to general anesthesia in children might be a potentially highrisk factor for learning and behavioral disorders. The mechanism of neurotoxicity induced by general anesthesia was not defined. miR-496 could regulate cerebral injury, while the roles of miR- 496 in neurotoxicity were not elucidated. Therefore, we aimed to investigate the effects of miR- 496 in neurotoxicity induced by propofol. Primary Prefrontal Cortical (PFC) neurons were isolated from neonatal rats and treated with propofol to induce neurotoxicity. Cell viability was detected by (3-(4,5-Dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The target relationship of miR-496 and Rho Associated Coiled-Coil Containing Protein Kinase 2 (ROCK2) was explored using luciferase assays. Propofol decreased cell viability, promoted cell apoptosis, and decreased the expression of miR-496 in PFC neurons in a dose-dependent manner. Overexpression of miR-496 attenuated neurotoxicity induced by propofol in PFC neurons. ROCK2 was a target of miR-496, and miR-496 oppositely modulated the expression of ROCK2. Besides, propofol increased the expression of ROCK2 through inhibiting miR-496 in PFC neurons. Overexpression of miR-496 attenuated propofol- induced neurotoxicity by targeting ROCK2 in PFC neurons. miR-496 was decreased in PFC neurons treated with propofol, and overexpression of miR-496 attenuated propofol-induced neurotoxicity by targeting ROCK2. miR-496 and ROCK2 may be promising targets for protecting propofol-induced neurotoxicity.


Prevalence and concordance of smoking among mothers and fathers within the Pacific Islands Families Study.
Cigarette smoking continues to contribute to the adverse mortality and morbidity rates for Pacific people in New Zealand. Using a large cohort study of Pacific families, this paper investigates the prevalence of smoking amongst Pacific mothers and fathers over three time-points, up to six years after the arrival of their child, to determine the concordance of both partners' reports of that smoking. Moreover, the patterns of smoking between partners were investigated over the three major Pacific ethnicities that reside in New Zealand (Samoan, Tongan and Cook Island Māori). Maternal self-report prevalence of smoking estimates ranged from 29.8% (1-year) to 33.6% (6-years). Paternal self-reported prevalence of smoking estimates were higher, and ranged from 37.9% (2-years) to 45.2% (6-years). The prevalence estimates for smoking in both mothers and fathers over all three measurement waves were higher than the 26.9% reported for Pacific people in the 2006/07 New Zealand Health Survey. No significant change in fathers' smoking prevalence over time was observed (p = 0.37); however a significant increase in mothers' smoking prevalence over time was noted (p = 0.002). Significantly, for about 25% of Pacific children both their parents were current smokers. Reducing infant exposure to tobacco smoke, by encouraging parents to quit smoking or banning smoking in the home and local environment (such as vehicles), is likely to bring about improved health outcomes for many Pacific children. Findings suggest that the interaction between parents should be considered rather than focusing on mothers' or fathers' smoking behaviour in isolation.


Benign transient hyperphosphatasemia associated with Epstein-Barr virus enteritis in a pediatric liver transplant patient: a case report.
Transient hyperphosphatasemia was found in a 3-year-old male liver transplant recipient. The condition was associated with diarrheal disease due to the Epstein-Barr virus (EBV). Immunosuppression was tapered and valganciclovir prescribed for 3 months, after which the diarrhea resolved and the EBV polymerase chain reaction assays became negative. After 6 months, alkaline phosphatase levels normalized. Isolated elevation of alkaline phosphatase in conjunction with enteric infection is a rare condition. No further diagnostic or therapeutic interventions except treatment of the underlying infection are needed, as this has been shown to be a benign, transient condition.


Mathematical modelling response of Pseudomonas aeruginosa to meropenem.
Widespread emergence of resistance to antimicrobial agents is a serious problem. The rate at which new agents are made available clinically is unlikely to keep up with these resistant pathogens, and there is an urgent need to accelerate antimicrobial agent development. We explored the use of mathematical modelling to guide selection of dosing regimens. Using time-kill studies data of Pseudomonas aeruginosa over 24 h, we developed a mathematical model to capture the dynamic relationship between a heterogeneous microbial population and meropenem concentrations. The microbial behaviour in response to meropenem over 5 days was predicted via computer simulation and subsequently validated using an in vitro hollow fibre infection model. Three parallel differential equations were used, each characterizing the rate of change of drug concentration, microbial susceptibility and microbial burden of the surviving population over time, respectively. Several model structures were explored; they differed in the adaptation of the microbial population over time. Various fluctuating concentration-time profiles of meropenem were experimentally examined, mimicking human elimination and repeated dosing. Using limited experimental data as inputs, the mathematical model was reasonable in qualitatively predicting microbial response (sustained suppression or regrowth due to resistance emergence) to various pharmacokinetic profiles of meropenem. Our results suggest that mathematical modelling may be used to predict microbial response to a large number of antimicrobial agent dosing regimens efficiently, and have the potential to be used to guide highly targeted investigation of dosing regimens in pre-clinical studies and clinical trials. The in vivo relevance of the modelling approach warrants further investigations.


The First Enantioselective Total Synthesis of (-)-trans-Dihydronarciclasine.
A feasible and enantioselective total synthesis of (-)-trans-dihydronarciclasine [(-)-1], a highly biologically active alkaloid, was devised starting from vanillin (8). The key step of this new synthesis was an asymmetric, organocatalytic Michael addition, in which an optically active nitropentanone [(-)-13] was obtained from a butenone derivative (12). Excellent enantioselectivity (>99% ee) was achieved using the (8S,9S)-9-amino(9-deoxy)epiquinine (16) organocatalyst. The target molecule can be prepared in 13 steps from compound (-)-13. The total synthesis has provided a facile and first access to the ent-form of naturally occurring (+)-trans-dihydronarciclasine, a highly potent cytostatic alkaloid.


Maturation of dendritic cells by bacterial immunomodulators.
Dendritic cells (DC) become fully functional upon maturation by various stimuli. We tested whether an immunostimulatory effect of clinically used immunomodulators (Luivac, Biostim, Ribomunyl, Imudon, Bronchovaxom) is caused by direct DC activation. We found that Luivac, Biostim and Ribomunyl have a very high DC stimulatory potential in vitro. The level of DC activation was comparable or higher than DC maturation induced by standard maturation stimuli, Poly (I:C) or lipopolysaccharide. Treated DC had activated phenotype, reduced phagocytic activity and they induced the proliferation of allogeneic T lymphocytes. These results are important for understanding the physiology of action of these widely prescribed agents. Administration of bacterial immunomodulators should be considered with care to avoid the potential risk of inducing an autoimmune disease. They could also be used as well-defined maturating agents in the protocols used for the ex vivo production of DC-based vaccines for clinical trials.


Relationships between corticosterone concentration and season, time of day and confinement in a wild reptile (tuatara, Sphenodon punctatus).
Seasonal and daily variation in basal plasma concentrations of corticosterone and the effect of short-term confinement on plasma corticosterone concentration were examined in wild adult male and female tuatara (Sphenodon punctatus) on Stephens Island, New Zealand. Males and females sampled immediately upon capture at night (active period) showed significant variation in basal plasma corticosterone among four seasons of the year, and females also showed variation in concentration between reproductive states sampled at the same time. Highest basal concentrations in females were seen in November, when the level in gravid females about to nest (4.45 +/- 0.66 ng/ml; mean +/- SE) was almost twice that in nonnesting females at the same time (2.48 +/- 0.30 ng/ml). Plasma samples collected from tuatara at dusk, middle of the night, dawn, and middle of the day showed no significant daily variation in corticosterone concentration in either summer or winter. In these samples, significant positive correlations between body temperature and log plasma corticosterone were observed in males in summer and winter, but not in females in either season. Mean corticosterone concentrations in tuatara held in cloth bags for 3 h were significantly higher than in free-roaming controls (P < 0.01), with mean concentrations in males about 23 times, and vitellogenic females 9 times, those of their respective controls. Plasma corticosterone concentrations measured in this stress study were compared with previously published concentrations for plasma sex steroids in the same individuals. Corticosterone was positively correlated with progesterone (both sexes), but not with testosterone (both sexes) or estradiol (measured in females only). In summary, wild adult tuatara have low basal levels of plasma corticosterone that vary seasonally, but not diurnally. As in other reptiles, corticosterone concentration shows a significant elevation in response to short-term confinement.


Transcriptomic analysis of equine chorioallantois reveals immune networks and molecular mechanisms involved in nocardioform placentitis.
Nocardioform placentitis (NP) continues to result in episodic outbreaks of abortion and preterm birth in mares and remains a poorly understood disease. The objective of this study was to characterize the transcriptome of the chorioallantois (CA) of mares with NP. The CA were collected from mares with confirmed NP based upon histopathology, microbiological culture and PCR for Amycolatopsis spp. Samples were collected from the margin of the NP lesion (NPL, n = 4) and grossly normal region (NPN, n = 4). Additionally, CA samples were collected from normal postpartum mares (Control; CRL, n = 4). Transcriptome analysis identified 2892 differentially expressed genes (DEGs) in NPL vs. CRL and 2450 DEGs in NPL vs. NPN. Functional genomics analysis elucidated that inflammatory signaling, toll-like receptor signaling, inflammasome activation, chemotaxis, and apoptosis pathways are involved in NP. The increased leukocytic infiltration in NPL was associated with the upregulation of matrix metalloproteinase (MMP1, MMP3, and MMP8) and apoptosis-related genes, such as caspases (CASP3 and CASP7), which could explain placental separation associated with NP. Also, NP was associated with downregulation of several placenta-regulatory genes (ABCG2, GCM1, EPAS1, and NR3C1), angiogenesis-related genes (VEGFA, FLT1, KDR, and ANGPT2), and glucose transporter coding genes (GLUT1, GLUT10, and GLUT12), as well as upregulation of hypoxia-related genes (HIF1A and EGLN3), which could elucidate placental insufficiency accompanying NP. In conclusion, our findings revealed for the first time, the key regulators and mechanisms underlying placental inflammation, separation, and insufficiency during NP, which might lead to the development of efficacious therapies or diagnostic aids by targeting the key molecular pathways.


Treatment of vitiligo.
Vitiligo, particularly in darker skinned individuals, is a psychosocial disaster. With patient education, proper therapeutic selection and persistence, favorable repigmentation can be achieved in the majority of individuals with vitiligo. Attention to the activity state of the disease, the type, location and extent of the vitiligo must be carefully balanced against the patient's expectations, time commitment and assumption of risks. In this review, Dr Taneja succinctly summarizes the wide range of therapeutic options available today for the vitiligo patient.


Replacing Sedentary Behavior With Physical Activity of Different Intensities: Implications for Physical Function, Muscle Function, and Disability in Octogenarians Living in Long-Term Care Facilities.
We investigated the associations of replacing sedentary behavior (SB) with physical activity of different intensities on the physical function of octogenarians living in long-term care facilities. This pooled study recruited 427 older adults aged 80 years and older (69.1% female; body mass index: 27.53). For 345 participants who provided valid data, we assessed device-measured time spent in SB, light-intensity physical activity (LIPA), and moderate to vigorous physical activity (MVPA). We assessed lower limb physical function, strength, mobility, and disability. We used compositional data analysis to investigate the associations of replacing SB with physical activity on the outcomes. Reallocation of SB to LIPA and MVPA was associated with a higher number of 30-second Chair Stand cycles (LIPA: +0.21, MVPA: +1.81; P < .001), greater peak force (LIPA: +11.96 N, MVPA: +27.68 N; P < .001), peak power (LIPA: +35.82 W, MVPA: +92.73 W; P < .001), peak velocity (LIPA: +0.03 m/s, MVPA: +0.12 m/s; P < .001), higher levels of grip strength (LIPA: +0.68 kg, MVPA: +2.49 kg; P < .001), and less time in the Time Up and Go (LIPA: -7.63 s, MVPA: -12.43 s; P < .001). Replacing SB with LIPA or MVPA is associated with physical function and disability of older adults living in long-term care facilities.


Implicit discount rates of vascular surgeons in the management of abdominal aortic aneurysms.
A growing empirical literature has investigated attitudes towards discounting of health benefits with regard to social choices of life-saving and health-improving measures and individuals' time preferences for the management of their own health. In this study, the authors elicited the time preferences of vascular surgeons in the context of management of small abdominal aortic aneurysms, for which the choice between early elective surgery and watchful waiting is not straightforward. They interviewed 25 of a random sample of 30 Swedish vascular surgeons. Considerable variation in the time preferences was found in the choices between watchful waiting and surgical intervention among the otherwise very homogeneous group of surgeons. The discount rates derived ranged from 5.3% to 19.4%. The median discount rate (10.4%) is similar to those usually reported for social choices concerning life-saving measures. The surgeons who were employed in university hospitals had higher discount rates than did their colleagues in county and district hospitals.


Effects of a standard transfer exercise program on transfer quality and activities of daily living for transfer-dependent spinal cord injury patients.
[Purpose] The objective of this study was to analyze the effect of a standard transfer exercise program on the transfer quality and activities of daily living (ADL) in wheelchair-dependent spinal cord injury patients. [Subjects and Methods] We randomly divided 22 patients into 2 groups. During the intervention period, one group received treatment with both conventional physical therapy and a standard sitting pivot transfer exercise program (experimental group, n=12) and the other group was managed solely with conventional physical therapy (control group, n=10). The standard transfer exercise program comprised of an independent and a dependent program. Exercises were conducted 30 minutes daily, 3 times per week, over a period of 6 weeks. All subjects were tested using a transfer assessment instrument (TAI) and spinal cord independence measure (SCIM) before and after the intervention. [Results] Compared to the control group, the intervention group scored higher on both the transfer assessment instrument (TAI Part 1, Part 2, TAI total score) and spinal cord independence measure tests (SCIM mobility room and toilet score; SCIM total score). [Conclusion] In conclusion, the standard transfer exercise program is an effective tool which improves transfer quality and the ability of wheelchair-dependent spinal cord injury patients to carry out their ADLs.


An urban survey of paediatric environmental health concerns: Perceptions of parents, guardians and health care professionals.
To conduct a survey in Edmonton, Alberta, to gather information regarding concerns about the influence of environmental factors on children's health and to use the information to set an agenda for the resources of the Paediatric Environmental Health Specialty Unit at Misericordia Hospital (Edmonton, Alberta). Two questionnaires with 28 closed-ended questions were developed to examine parents', guardians' and health care professionals' concerns. They comprised items about six environmental factors (air, water and food quality; household supplies; radiation; and waste disposal). Health care professionals were also asked four questions about their knowledge of and their needs in Paediatric Environmental Health. Parents and guardians attending the public health centres and nurses working therein received questionnaires. Physicians were surveyed by e-mail. After verification, the questionnaire data from 400 parents or guardians and 152 health care professionals were used for analyses. Results from contingency table, Hotelling's T² and effect size analyses revealed similarities in the levels of concern in both groups, and the results were combined. The greatest concern of both groups was with environmental tobacco smoke, followed by pesticides in water. Concerns about six additional environmental elements were also expressed. The health care professionals showed a high level of concern about the need for resources, specific training and public education regarding paediatric environmental health. A significant level of concern was consistently found between the two groups studied, regardless of professional training. The highest level of concern was with a well-documented topic (ie, environmental tobacco smoke). Less concern associated with decreased documentation calls for increasing the knowledge of society, including health care professionals, to address the adverse effects of environmental factors on children.


[Treatment with neutrons: hadrontherapy part II: physical basis and clinical experience].
Neutrons have radiobiological characteristics, which differ from those of conventional radiotherapy beams (photons) and which offer a theoretical advantage over photons to fight radioresistance by the differential relative biological effect of them between normal and tumour tissues. Neutron therapy beneficed of great interest between 1975 and 1985. Many of phase III trials were conducted and indications have been definitively deducted of them. After briefly describing the properties of neutron beams, this review discusses the indication of neutron therapy on the basis of the clinical results. Salivary, prostate tumours and sarcomas are the main indications of neutron therapy. In concern to the prostate cancers, other alternative treatments reduce the neutron therapy field. For sarcomas, the lack of randomised trials limits the impact of the interest of neutrons. For other tumours, the ratio benefice/risk of neutron therapy is inferior to these obtained with photons and they could not be considered like classical indications.


[Postgraduates' training as laboratory physicians/clinical pathologists in Japan--board certification of JSLM as a mandatory requirement for chairpersons of laboratory medicine].
The educational committee of the Japanese Society of Laboratory Medicine(JSLM) proposed a revised laboratory medicine residency curriculum in 1999 and again in 2001. The committee believes that present undergraduate clinical training is insufficient and that Japanese medical graduates need clinical training for two years after graduation. This two years training should be a precondition for further postgraduate training in laboratory medicine and should include fundamental clinical skills(communication skills, physical examination and common laboratory procedures such as Gram's stain, Wright-Giemsa stain and urinalysis). After the two years training, the minimal training period of laboratory medicine should be three years, and should include: 1) Principles, instrumentation and techniques of each discipline including clinical chemistry, clinical hematology, clinical microbiology, clinical immunology, blood banking and other specific areas. 2) The use of laboratory information in a medical setting. 3) Interaction of the laboratory physician with laboratory staff, physicians and patients. With good on-the-job training and 24 hours on-call duties, laboratory physicians are expected to perform their tasks, including laboratory management, effectively. They should have appropriate educational background and should be well motivated. The background and duties of the laboratory physicians often reflect the institutional needs and personal philosophy of the chairperson of their department. At the moment, few senior physicians in Japan have qualifications in laboratory medicine and are unable, therefore, to provide the necessary guidance to help the laboratory physicians in their work. I therefore believe that the board certification of JSLM should be regarded as mandatory for chairpersons of laboratory medicine. Our on-call service system can enhance the training in laboratory medicine, and improve not only laboratory quality assurance but patients' care as well.


Temporal artery compression sign--a novel ultrasound finding for the diagnosis of giant cell arteritis.
In patients with suspected giant cell arteritis (GCA), a search for the perivascular halo sign, a sophisticated color duplex ultrasound (CDU) finding, at experienced centers reliably identifies inflamed temporal arteries (TA). We tested whether TA compression in patients with GCA, a simple, largely operator-independent maneuver, elicits contrasting echogenicity between the diseased artery wall and the surrounding tissue (compression sign). 80 individuals with suspected GCA were prospectively enrolled in this single-center study. In all study participants, bilateral ultrasound examination of the TA established the presence/absence of the halo and compression sign. A positive compression sign was defined as visibility of the TA upon transducer-imposed compression of the artery. Based on ACR criteria, a team of specialized physicians independently grouped patients as GCA versus non-GCA. 43/80 study participants were grouped as GCA. Both the halo sign and the compression sign were positive in 34/43 patients in the GCA group, and negative in all 37/37 of the non-GCA group, resulting in a sensitivity of 79 % and a specificity of 100 % for both the halo and the compression sign. In this cohort of individuals with suspected GCA, the halo sign and the compression sign were equal in their diagnostic performance. The simplicity of the compression sign suggests a level of reliability warranting further evaluation.


Neuropsychological outcome following anterior temporal lobectomy in patients with and without the syndrome of mesial temporal lobe epilepsy.
The nature, pattern, and degree of neuropsychological change following anterior temporal lobectomy (ATL) were examined as a function of the presence or absence of the syndrome of mesial temporal lobe epilepsy (MTLE). Fifty-four patients exhibited the syndrome of MTLE, while 34 patients were without the syndrome (non-MTLE). The test-retest performance of a group of 40 epilepsy patients who did not undergo surgery was used to derive regression-based estimates of test-retest change. Overall, the MTLE group did not show significant cognitive decline following ATL. In contrast, the left non-MTLE group showed significant declines on verbal memory, confrontation naming, and verbal conceptual ability. Further, verbal memory was the most substantial area of decline, and was independent of seizure outcome. Clinical and theoretical implications of these findings are discussed.


Diagnosis of a liver abscess with Ga-67 and radiocolloid tomography.
A 46 year-old white male with fever of unknown origin demonstrated a multiloculated hepatic cyst on abdominal CT. Persistent fever and leukocytosis prompted Tc-99m Sulfur colloid liver-spleen and gallium-67 citrate imaging to identify a possible liver abscess. SPECT imaging provided pertinent clinical information that allowed the diagnosis of abscess to be made.


Operating room efficiency.
The operating room is the financial hub of any hospital, and maximizing operating room efficiency has important implications for cost savings, patient satisfaction, and medical team morale. Over the past decade, manufacturing principles and processes such as Lean and Six Sigma have been applied to various aspects of healthcare including the operating room. Although time consuming, process mapping and deep examinations of each step of the patient journey from pre-operative visit to post-operative discharge can have multiplicative benefits that extend from cost savings to maintaining the focus on improving quality and patient safety.


[A case of Churg-Strauss syndrome with short duration from the onset of asthma to diagnosis of vasculitis].
A 68-year-old woman was hospitalized because of bronchial asthma and a high myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) level. She had suffered from rhinitis from one year before hospitalization, body weight loss from three months before, and asthma from one month before. On admission, she complained of dyspnea and body weight loss of over 6 kg. On laboratory tests, high MPO-ANCA and urinary abnormalities were found. On the next day, a renal biopsy was performed and histology showed necrotizing vasculitis with cellular crescents. Churg-Strauss syndrome (CSS) was diagnosed on the basis of the clinical course and histological findings. Prednisolone therapy induced rapid symptom remission, which was achieved within one month from the onset of asthma to the diagnosis of CSS. Early diagnosis and early care led to a good prognosis.


[LEOPARD syndrome].
LEOPARD syndrome with multiple lentigines (cardiomyopathic lentiginosis) is a rare, genetically predetermined disease with autosomal dominant inheritance. Prevalence of this syndrome is unknown. One of pathognomonic clinical manifestations of this syndrome is the presence of multiple lentiginous pigment spots all over the body. The most common cardiac manifestation (approximately 80%) is myocardial hypertrophy. We presented a rare clinical case of detecting LEOPARD syndrome with multiple lentigines in a 32-year old female patient with major manifestations evident as pronounces morpho-functional alterations, myocardial hypertrophy, and heart rhythm disorders.


Hormonal regulation of rat hypothalamic neuropeptide mRNAs: effect of hypophysectomy and hormone replacement on growth-hormone-releasing factor, somatostatin and the insulin-like growth factors.
Hormonal feedback regulation of hypothalamic peptides putatively involved in growth hormone (GH) regulation has been studied by measurement of steady-state mRNA levels in male hypophysectomized rats with or without thyroid hormone, corticosterone, testosterone or GH replacement. Hypothalamic GH-releasing factor (GRF) mRNA levels increased progressively following hypophysectomy to 420% of sham levels after 15 days while hypothalamic insulin-like growth factor I (IGF-I) and insulin-like growth factor II (IGF-II) mRNA levels decreased to less than 40% of sham levels. Whole hypothalamic somatostatin mRNA levels were not significantly different from sham. One week of continuous GH infusion restored hypothalamic IGF-I mRNA to levels (95%) indistinguishable from those in sham-operated controls but had no effect on either IGF-II or GRF mRNA. Thyroid hormone, corticosterone and testosterone treatment without GH had no effect on the hypophysectomy-induced reduction of either IGF-I or IGF-II mRNA levels but reversed the elevation of GRF mRNA. We conclude that hypothalamic IGF-I may be involved in GH feedback regulation and thus may function as a hypothalamic modulator of GH. In contrast, IGF-II may be regulated by one of the pituitary trophic hormones but not by GH or the target hormones tested. Finally, hypothalamic GRF mRNA regulation appears to be complex and may include target hormone feedback.


Treponema paraluis-cuniculi infection in a commercial rabbitry: epidemiology and serodiagnosis.
The epidemiology of Treponema paraluis-cuniculi infection in a commercial rabbit breeding facility was described using several serologic tests. The Venereal Disease Research Laboratory, rapid plasma reagin, microhemagglutination and fluorescent treponemal antibody-absorption tests were used to detect antibodies to T paraluis-cuniculi. Young adult New Zealand white rabbits, tested prior to entry into the breeding program, were nearly always free of T paraluis-cuniculi infection. In adult females, the prevalence of T paraluis-cuniculi infection increased with parity; females para 6 or greater were usually seropositive. Most adult males seroconverted within 6 months of entering the breeding program; all males were seropositive after 12 months in the breeding program. This suggested that T paraluis-cuniculi spreads mainly by horizontal transmission during breeding in adult rabbits. Of the two nontreponemal antigen tests used, the Venereal Disease Research Laboratory test was more sensitive, whereas the rapid plasma reagin test was more specific in detecting T paraluis-cuniculi infection; the fluorescent treponemal antibody-absorption test was used as the confirmatory treponemal antigen test. However, neither nontreponemal antigen test was completely satisfactory. On the other hand, the sensitivity and specificity of the microhemagglutination test compared favorably with the fluorescent treponemal antibody-absorption test. Since the microhemagglutination test combines desirable features of both a screening and verification procedure, it should be the test of choice for detection of T paraluis-cuniculi infection.


Induction of heme-binding protein 23/peroxiredoxin I gene expression by okadaic acid in cultured rat hepatocytes.
Heme-binding protein 23 (HBP23), also termed peroxiredoxin I (Prx I), is an antioxidant protein that is induced by various oxidative stress stimuli. HBP23/Prx I has thioredoxin-dependent peroxidase activity and noncovalently binds the prooxidant heme with high affinity. To investigate the regulatory role of cellular phosphorylation and dephosphorylation events on hepatic HBP23/Prx I gene expression, primary cultures of rat hepatocytes were treated with okadaic acid (OA) which is a specific inhibitor of the serine threonine protein phosphatases 1 and 2A. In hepatocyte cultures HBP23/Prx I was highly expressed for up to 5 days and, both protein and mRNA levels of HBP23/Prx I were induced by OA. The time kinetics of OA-dependent HBP23/Prx I mRNA upregulation were coordinate to that of heme oxygenase (HO)-1, which is the inducible isoform of the rate-limiting enzyme of heme-degradation. In contrast to HO-1, however, induction of HBP23/Prx I mRNA by OA was downregulated by dibutyryl-cAMP, and was enhanced by the specific protein kinase A inhibitors KT5720 and H-89. HBP23/Prx I induction by OA occurred on the transcriptional level as determined by studies with actinomycin D and nuclear run-off assays.


(Z)-7-dodecenyl acetate: a supernormal stimulus of Trichoplusia ni (Hübner) [Lepidoptera: Noctuidae] sex pheromone behavior.
Males discriminate between the single most important individual component of the sex pheromone of the female cabbage looper, Trichoplusia ni (Hübner), (Z)-7-dodecenyl acetate (Z7-12:Ac), and a mixture containing Z7-12:Ac and the other five putative components. The manifestation of discrimination is not an enhancement of captures by the mixture, rather, it is a reduction of captures in a paired trap baited with Z7-12:Ac by itself. Previous experiments showed that either or both of (Z)-7-tetradecenyl acetate (Z7-14:Ac) and (Z)-9-tetradecenyl acetate (Z9-14:Ac) were responsible for this discrimination. This report provides evidence that Z7-14:Ac is more active than Z9-14:Ac, which appears to have no demonstrable effect on behavior. The results are discussed with reference to the behavior that is effected by the above three components, the composition of the native sex pheromone, and whether or not Z7-12:Ac might be a supernormal releaser of behavior.


BIOIMPEDANCE: NEW APPROACH TO NON-INVASIVE DETECTION OF LIVER FIBROSIS - A PILOT STUDY.
Fibrosis are common structural hepatic change in patients with chronic hepatitis. Liver biopsy is the gold standard for determining the extent of liver fibrosis. Considering the technical difficulties and cost, improvements in non-invasive screening tools are greatly needed. Bioimpedance have been shown to be safe to evaluate tissue fibrosis. To assess the utility of using monofrequential bipolar bioimpedance for the detection of severity of liver fibrosis consistent with chronic viral hepatitis C infections. One hundred and ten patients were studied prospectively and formed two groups according to the lab tests results for the detection of HCV, ALT and AST: Group 1 Control (n=50 healthy patients with HCV negative and with ALT and AST values within the normal clinical range) and Group 2 Positive (n=60 patients positive for anti-HCV positive) which were biopsied. All patients underwent an examination with an Electro Sensor Complex, bioimpedance technology. To compare the groups 1 and 2, the ROC curves was used to determine the specificity and sensitivity of the bioimpedance to detect liver fibrosis. To identify liver fibrosis severity the Group 2 Positive was subdivided according to the liver biopsy results (Metavir fibrosis score) into: Sub Group 2A (F0-F1 n=25) - patients without or with minimal portal fibrosis and Sub Group 2B (F3-F4 n=20) patients with numerous septa/cirrhosis. A statistical analysis was conducted to analyze the bioimpedance data differences in delta of the conductance. From the comparison between Groups 1 and 2: 1) The delta value for conductance in the pathway representing the right foot-left hand minus left hand-right foot demonstrated a sensitivity of 85% and a specificity of 78% with a cutoff value ≤5 and P=0.0001. 2) For the comparison between Sub Group 2A (Metavir F0+F1) and Sub Group 2B (Metavir F3+F4), the neural network for the Electro Sensor Complex data demonstrated a sensitivity of 85% and a specificity of 72% with a cutoff probability >50% and P=0.001. AUCROC=0.81. Bioimpedance technology had good level sensitivity and acceptable specificity for detecting liver fibrosis using delta of the conductance. There is a potential for the use of bioimpedance technology as non-invasive approaches for screening of liver fibrosis.


Suspicion, screening, and diagnosis of wild-type transthyretin amyloid cardiomyopathy: a systematic literature review.
Wild-type transthyretin amyloid cardiomyopathy (ATTRwt CM) is a more common disease than previously thought. Awareness of ATTRwt CM and its diagnosis has been challenged by its unspecific and widely distributed clinical manifestations and traditionally invasive diagnostic tools. Recent advances in echocardiography and cardiac magnetic resonance (CMR), non-invasive diagnosis by bone scintigraphy, and the development of disease-modifying treatments have resulted in an increased interest, reflected in multiple publications especially during the last decade. To get an overview of the scientific knowledge and gaps related to patient entry, suspicion, diagnosis, and systematic screening of ATTRwt CM, we developed a framework to systematically map the available evidence of (i) when to suspect ATTRwt CM in a patient, (ii) how to diagnose the disease, and (iii) which at-risk populations to screen for ATTRwt CM. Articles published between 2010 and August 2021 containing part of or a full diagnostic pathway for ATTRwt CM were included. From these articles, data for patient entry, suspicion, diagnosis, and screening were extracted, as were key study design and results from the original studies referred to. A total of 50 articles met the inclusion criteria. Of these, five were position statements from academic societies, while one was a clinical guideline. Three articles discussed the importance of primary care providers in terms of patient entry, while the remaining articles had the cardiovascular setting as point of departure. The most frequently mentioned suspicion criteria were ventricular wall thickening (44/50), carpal tunnel syndrome (42/50), and late gadolinium enhancement on CMR (43/50). Diagnostic pathways varied slightly, but most included bone scintigraphy, exclusion of light-chain amyloidosis, and the possibility of doing a biopsy. Systematic screening was mentioned in 16 articles, 10 of which suggested specific at-risk populations for screening. The European Society of Cardiology recommends to screen patients with a wall thickness ≥12 mm and heart failure, aortic stenosis, or red flag symptoms, especially if they are >65 years. The underlying evidence was generally good for diagnosis, while significant gaps were identified for the relevance and mutual ranking of the different suspicion criteria and for systematic screening. Conclusively, patient entry was neglected in the reviewed literature. While multiple red flags were described, high-quality prospective studies designed to evaluate their suitability as suspicion criteria were lacking. An upcoming task lies in defining and evaluating at-risk populations for screening. All are steps needed to promote early detection and diagnosis of ATTRwt CM, a prerequisite for timely treatment.


Reversible thioridazine-induced magnetic resonance imaging-documented pituitary enlargement associated with hyperprolactinemia.
To document a case of reversible thioridazine-induced pituitary enlargement associated with hyperprolactinemia in a patient with schizophrenia. We describe a 19-year-old woman with paranoid schizophrenia who was taking thioridazine (a phenothiazine), in whom hyperprolactinemia, galactorrhea, oligomenorrhea, and a reversible anatomic pituitary abnormality developed. Serial magnetic resonance imaging (MRI) studies were used to assess the status of the pituitary gland during various pharmaceutical therapies. Laboratory evaluation revealed increased serum prolactin (PRL) levels that ranged from 76 to 135 mg/L. Results of thyroid function tests were normal, and gonadotropins and estradiol levels were low, consistent with hyperprolactinemia. MRI revealed asymmetric enlargement of the right side of the pituitary gland. Discontinuing the thioridazine therapy resulted in normalization of the serum PRL and resolution of the pituitary abnormality. Subsequent worsening of the patient's psychiatric condition necessitated a course of electroconvulsive therapy and initiation of treatment with clozapine, a D4 dopamine receptor antagonist. At 1-year follow-up, at which time the patient was maintained on clozapine and was not taking thioridazine, both serum PRL levels and MRI findings remained normal. Our patient was shown to have asymmetric pituitary enlargement associated with thioridazine-induced hyperprolactinemia, which reversed when use of the drug was discontinued. In patients with serum PRL levels in excess of 100 mg/L during antipsychotic drug therapy, evaluation for a prolactinoma is warranted.


Ability of chronic wound fluids to degrade peptide growth factors is associated with increased levels of elastase activity and diminished levels of proteinase inhibitors.
The stability of peptide growth factors exposed to fluids from healing surgical wounds and from nonhealing chronic wounds was examined in vitro. (125)I-Labeled transforming growth factor-beta1 or platelet-derived growth factor-BB was incubated with fluids from healing surgical wounds and fluids from venous stasis or pressure ulcers. Fluids from healing surgical wounds had no appreciable effect on the level of (125)I corresponding to intact growth factor. In contrast, incubation with fluids from several venous stasis or pressure ulcers resulted in significant degradation of these growth factors. Degradation was blocked by broad-spectrum serine proteinase inhibitors and by specific inhibitors of neutrophil elastase. Levels of elastase activity in wound fluids correlated with the ability to degrade peptide growth factors. Further comparisons showed qualitative and quantitative differences in the endogenous proteinase inhibitors, alpha2-macroglobulin and alpha1-antiproteinase. These results could explain, in part, the variable growth factor levels which have been found in chronic wounds. More importantly, the ability of some chronic nonhealing wounds to rapidly degrade exogenously added growth factors has important implications with regard to past and future clinical attempts to use peptide growth factors to treat these types of problem wounds.


[Regulation of naotai recipe on the expression of HIF-lα/VEGF signaling pathway in cerebral ischemia/reperfusion rats].
To observe the therapeutic angiogenesis effect of naotai recipe (NR) on local ischemia/reperfusion (I/R) injury of rats by observing signaling pathway of hypoxia-inducible factor-lα (HIF-1α) and vascular endothelial growth factor (VEGF). Totally 120 Sprague-Dawley (SD) rats were randomly divided into 4 groups, namely, the normal control group (n =12), the sham-operation group (n =12), the I/R model group (n =48), and the NR group (n =48). Cerebral I/R injury models were established using thread suture method. Rats in the I/R model group and the NR group were sub-divided into 4 sub-groups according to the 1st, 3rd, 5th, and 7th I/R day (n =12). The phenomenon of neovasculization was observed by immunofluorescence staining. The protein and mRNA expression levels of HIF-la, VEGF-A, and VEGFR II receptor were detected by RT-PCR. There were a large amount of labels for neovasculization in the ischemic area of the NR group. Double-immunofluorescence labeling [vWF (red) and BrdU (green)] was observed in the NR group. Compared with the model group, the HIF-1α protein expression was obviously enhanced on the 1 st day of I/R (P <0.01), and the VEGF protein expression started to enhance on the 3rd day in the NR group (P <0.01). The VEGFR protein expression level was the highest in the NR group on the 5th day of I/R (P <0.01). The protein expression of VEGF and HIF-1α started to decrease on the 7th day of I/R. NR could strengthen angiogenesis after I/R by elevating the expression of HIF-lα and activating HIF-lα/VEGF signaling pathway.


Association of systemic antibody response against polyethylene terephthalate with inflammatory serum cytokine profile following implantation of differently coated vascular prostheses in a rat animal model.
Experimental studies demonstrated antibodies against matrix and coating of polyester-based vascular prostheses. Thus, this study examined associations of these antibodies with serum cytokines (IL-2, IL-4, and IL-10) and local inflammatory reactions. Rats (n = 8/group) intramuscularly received prosthesis segments [PET-C, PET-G, and PET-A groups: polyethylene terephthalate (PET)-based prostheses coated with bovine collagen and gelatin or human serum albumin, respectively; uncoated polytetrafluoroethylene-based (PTFE) prosthesis], with sham-operated controls. Blood was drawn pre-operatively and weekly until day 22. Polymer-specific or coating-specific antibodies and cytokines were detected by enzyme immunoassays, inflammatory reactions were immunohistochemically evaluated on day 23. Polymer-specific antibodies were detected in all PET-groups using uncoated PET as antigenic target, but not for PTFE or controls, coating-specific antibodies only for PET-A. IL-10 was increased in all PET-groups and correlated with polymer-specific antibodies for PET-G and PET-A. IL-2 was increased for PET-A, but overall correlated with PET-specific antibodies. IL-4 remained unchanged in all groups. Intense local inflammatory reactions (ED1+ /ED2+ macrophages and T lymphocytes) were found within all PET-groups, but only minor for PTFE or controls. In conclusion, PET-specific antibodies were associated with increased IL-10 and along with concurrent coating-specific antibodies also with increased IL-2, indicating a specific T cell response. Thus, matrix and/or coating of polymeric vascular prostheses elicit distinct systemic immune reactions, probably influencing local inflammatory reactions.


[Squamous cell carcinoma of the external ear. A carcinoma of old age which requires individualized therapy planning].
Data for all patients with ear malignancies being operated in our department between August 1988 and March 2001 were retrospectively analyzed for tumor localisation, stage, biometric data, anesthesiological risk factors, therapy and recurrence of the disease. Thirty of 79 patients (29 male, one female; average age 77.2 years, range 54-99 years) with cutaneous malignancies of the external ear were diagnosed as SCC ( n=32 SCC). A total of 17 SCC were smaller than 2 cm, 12 were between 2-5 cm, and three were larger than 5 cm. Only two patients had regional nodal disease, none had distant metastases. The anesthesiological risk was estimated according to the recommendations of the American Society of Anesthesiologists (ASA); 16/30 patients were classified as group 3 or 4, having severe general disease with a decrease in vitality or even vital risks. A total of 24 SSC were primarily operated under local anesthesia. Depending on histology, localisation and size of the SCC local excision, partial or total removal of the auricle was performed. In the remaining 8/32 cases, the primary intervention was performed under general anesthesia, mostly in combination with an ipsilateral neck dissection and a superficial parotidectomy. In 8/32 cases, the SCC had to be re-operated after primary R1 resection. Altogether, eight patients received radiotherapy. In 5/32 cases there was a recurrence of the disease. The average follow-up period of the 13 patients who are still alive is 50 months (17-113). One patient died as a result of the metastasized SCC and 16 patients died due to other diseases. Considering the high age and the age-associated general diseases of the patients with SCC of the auricle, differentiation between a radical concept of therapy and its risks and possible therapy-related damage is important. Therefore, individual concepts such as partial removal of the pinna without neck dissection and parotidectomy for the N(0) stage are justified if relevant anesthesiological risk factors have to be taken into account.


[The validity of various audiometric testing methods in tumor-induced hearing disorders].
In order to study the diagnostic possibilities for detecting acoustic neuromas respectively tumors of the cerebello pontine angle 60 patients with secured tumor (op. confirmed) were preoperatively examined audiologically . The test results were worked out statistically and checked of their validity in respect of the diagnosis. It could be found, that the results of the conventional audiometry, if taken in its entirety, approved a secure diagnosis in most of the cases; though very discretely marked constellations of test results had to be considered. Routine-audiometric failures were essentially restricted to patients which were deaf or had a high-grade hearing loss ( Lehnhardt 1983). The recordings of auditory brain stem responses of them selves showed in all cases a result in the sense of retrocochlear hearing disorder, not only with regard to prolonged absolute latency times of JV/P6 but also of prolonged interpeak latency times between JI and JV. In cases of monaurale deafness, the ERA supplied a secure criterion for a brain stem disorder because of delayed latency times on the not affected side.


Durability of adherence to antiretroviral therapy on initial and subsequent regimens.
There is uncertainty regarding the durability of adherence to antiretroviral therapy. This study is a retrospective review of previously antiretroviral naïve patients initiating therapy between 1997 and 2002. Antiretroviral adherence was calculated using prescription refill data and was analyzed over time on an initial regimen and on sequential antiretroviral regimens. Three hundred forty-four patients were included. The median lengths of the first, second, and third regimens were stable at 1.7 years, 1.2 years, and 1.5 years, respectively (p = 0.10). In multivariate analysis the factor most significantly associated with earlier initial regimen termination was poor adherence. On an initial regimen, adherence decreased over time and declined most rapidly in patients with the shortest regimens (4 to <16 months, -43% per year), followed by patients with intermediate regimen duration (16 to <28 months, -19% per year), and then patients with longer regimens (>/=28 months, -5% per year). In patients progressing to a third regimen, there was a trend toward decreasing adherence over successive regimens. In conclusion, sequential antiretroviral regimens are of similar lengths, with adherence being highly associated with first regimen duration. Adherence decreases during an initial regimen and on sequential antiretroviral regimens. Effective and durable interventions to prevent declining adherence are needed.