[Dynamic changes of serum antibody titer in a rabbit model of Acanthamoeba keratitis].
Ten healthy New Zealand white rabbits were randomly divided into two groups named as experiment group (n=8) and normal control group (n=2). Left eyes were for experiment, right eyes served as control. New Zealand rabbits were each injected by subconjunctival route with hydrocortisone for three days, and then Acanthamoeba keratitis was induced by intrastromal injection of live Acanthamoeba healyi trophozoites and cysts. Eyes in control group were injected with equivalent volume of physiological saline. Corneal lesions of rabbits were recorded every day after injection, etiological diagnosis was carried out by corneal scraping. Blood samples were examined for serum antibody titer by ELISA. Corneas were removed for pathological examination. Corneal scraping and corneal histopathologic examination proved that experiment eyes were infected by Acanthamoeba, and appeared typical manifestations and pathological changes of Acanthamoeba keratitis. Serum antibody titer raised continuously with infection time and reached the highest level (A450 value=2.2358) on the 28th days post-infection, then began to decline and remained higher level than the control until the rabbits were sacrificed. In control group, no significant change in antibody titer had taken place.


Double aortic arch presenting with a foreign object in the oesophagus: a case report and imaging diagnosis.
In this article, we report a rare case of double aortic arch. The case presented initially with a foreign object in the oesophagus. The patient was a 2-year-old boy, who was referred with primary symptoms of tussis (15 days) and emesis (2 days). He had a history of ingesting a coin. Routine chest X-ray indicated a rounded, metal foreign object in the upper oesophagus. A half-Yuan coin was removed by gastroduodenoscopy. Echocardiographic imaging suggested that the patient had double aortic arch, which was subsequently diagnosed by CT angiography with three-dimensional reconstruction. The right subclavian artery arose from the right loop of the double aortic arch. The left subclavian artery as well as left and right common carotid arteries had distinct origins from the left aortic arch. Imaging also indicated atresia of the distal left arch. The patient underwent corrective surgery and made a full recovery. Despite the rarity, double aortic arch should be considered when patients present with a foreign object in the oesophagus. Echocardiography and CT angiography can inform the diagnosis.


Safe use of rectal suppositories and enemas with adult patients.
Medications that are given via the rectal route are prescribed for a variety of reasons and have either a local or systemic effect. The administration of suppositories and enemas is an intimate procedure which has the potential to cause embarrassment and discomfort for the patient. This article outlines the reasons for the use of rectal medications and recommends a procedure to be followed when giving them.


A prospective 15-year follow-up study of mandibular fixed prostheses supported by osseointegrated implants. Clinical results and marginal bone loss.
In this prospective study 47 edentulous patients were treated with mandibular fixed prostheses supported by osseointegrated Brånemark implants and followed for 12 to 15 years. Three (1%) of the 273 inserted implants were lost, two before and one six years after placement of the fixed prosthesis. The cumulative success rate (CSR) of the implants was 98.9% both after 10 and 15 years. None of the fixed prostheses was lost and at the last follow-up, all patients had stable fixed prostheses in function (CSR 100%). The marginal bone loss around the implants was small, on average 0.5 mm during the first post surgical year and thereafter about 0.05 mm annually. More bone was lost around the anterior implants than around the most posterior ones. Smoking and poor oral hygiene had significant influence on bone loss, while occlusal loading factors such as maximal bite force, tooth clenching and length of cantilevers were of minor importance. It is concluded that the long-term results of the mandibular implant treatment were extremely successful, regarding both the fixed prostheses and implant stability. Bone resorption around the implants, albeit limited, was influenced by several factors, smoking and oral hygiene appeared to be most important.


Heterotopic ossification resection after open periarticular combat-related elbow fractures.
A retrospective review was performed to evaluate the outcomes and complications following heterotopic ossification (HO) resection and lysis of adhesion procedures for posttraumatic contracture, after combat-related open elbow fractures. From 2004 to 2011, HO resection was performed on 30 blast-injured elbows at a mean 10 months after injury. Injuries included 8 (27%) Gustilo-Anderson type II fractures, 8 (27%) type III-A, 10 (33%) III-B, and 4 (13%) III-C. Mean preoperative flexion-extension range of motion (ROM) was 36.4°, compared with mean postoperative ROM of 83.6°. Mean gain of motion was 47.2°. Traumatic brain injury, need for flap, and nerve injury did not appear to have a significant effect on preoperative or postoperative ROM. Complications included one fracture, six recurrent contractures, and one nerve injury. The results and complications of HO resection for elbow contracture following high-energy, open injuries from blast trauma are generally comparable to those reported for HO resection following lower energy, closed injuries.


The natural history of repaired myelomeningocele.
With aggressive management based on careful evaluation, children afflicted with myelomeningocele can achieve their maximum potential. Sonography, MR imaging and CT myelography all play important roles in their evaluation.


Oral absorption of chlortetracycline in turkeys: influence of citric acid and Pasteurella multocida infection.
Plasma and tissue concentrations, following the oral administration of the antibiotic chlortetracycline (CTC) alone or with citric acid, were determined in healthy and infected (Pasteurella multocida) turkeys. The principal results were: 1) The dose (of CTC) versus plasma level relationship was nearly linear. 2) Addition of citric acid to an oral preparation produced significantly higher plasma levels when divalent cations Ca2+ (.3 g/liter) and Mg2+ (.1 g/liter) were present in the drinking water and dosage solution than when citric acid was omitted. 3) The concentration of CTC was considerably higher in the liver and kidney than in the muscle and brain. 4) Birds infected with P. multocida had significantly higher plasma levels than healthy birds. 5) Oral administration of CTC increased the survival rate of the birds infected with P. multocida.


The pathology of psittacine beak and feather disease.
Psittacine beak and feather disease is characterised by loss of feathers, abnormally shaped feathers and overgrowth and irregularity of the surface of the beak. The disease occurs in a number of psittacine species including the Sulphur-crested Cockatoo, Lovebirds , Budgerigars and Galahs . The abnormal appearance of feathers and beak is due to a dystrophic process within the epidermis of the feather and beak. The process consists of epidermal cell necrosis, epidermal hyperplasia and hyperkeratosis. Many of the feather abnormalities are due to retention of a hyperkeratotic feather sheath. A characteristic microscopic finding is the presence of macrophages containing purple intracytoplasmic inclusions in affected epidermis and feather pulp. The inclusions consist of aggregates of particles 17 to 22 nm in diameter. Similar but smaller inclusions occur in epidermal cells. In addition, non-suppurative inflammation occurs in the feather pulp. The findings are suggestive of a viral infection.


Conditional modulation of membrane protein expression in cultured cells mediated by prion protein recognition of short phosphorothioate oligodeoxynucleotides.
We demonstrate that the levels of native as well as transfected prion protein (PrP) are lowered in various cell lines exposed to phosphorothioate oligodeoxynucleotides (PS-DNA) and can be rapidly reverted to their normal amounts by removal of PS-DNA. This transient modulation was independent of the glycosylation state of PrP, and in addition, all three PrP glycoforms were susceptible to PS-DNA treatment. Deletion of the N-terminal domain (amino acids 23-99), but not of the other domains of PrP, abrogated its PS-DNA-mediated down-regulation. PrP versions localized in the mitochondria, cytoplasm, or nucleus were not modulated by PS-DNA, indicating that PrP surface exposure is required for executing this effect. Proteins that in their native forms were not responsive to PS-DNA, such as thymocyte antigen 1 (Thy1), Doppel protein (Dpl), green fluorescent protein (GFP), and cyan fluorescent protein (CFP), became susceptible to PS-DNA-mediated down-regulation following introduction of the N terminus of PrP into their sequence. These observations demonstrate the essential role of the N-terminal domain for promoting oligonucleotide-mediated reduction of the PrP level and suggest that transient treatment of cultured cells with PS-DNA may provide a general method for targeted modulation of the levels of desired surface proteins in a conditional and reversible manner.


Flowering Stage and Daytime Affect Scent Emission of Malus ioensis "Prairie Rose".
Flowering crabapple is an important ornamental flower. It is vital to understand the floral scent properties and the associated release dynamics for carrying out fragrant flower breeding or floral regulation of crabapple. Static headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry was used to detect the volatile compounds in Malus ioensis "Prairie Rose" flowers at different flowering stages and at different day-night time. The results showed that methylheptenone, phenylethanol, geranylacetone, 2-(4-methoxyphenyl)ethanol, α-cedrene were the major compounds in M. ioensis "Prairie Rose", but the compounds released during different stages and different day-night time were significantly different (P < 0.0001). A total of 25 volatile compounds were identified from the four flowering stages. The floral scents in the initial and flowering stages were the most similar (dissimilarity 0.21). The main compounds in these two stages were geranylacetone and methylheptenone, and the contents of geranylacetone and phenylethanol were positively correlated with the flowering stages. From the bud stage to the end of flowering, the total amount of volatile compounds released showed an initial increase followed by a decrease and the amounts of compounds released during the initial flowering stage were the highest. The aliphatic and benzenoids content was significant higher in the daytime than at night. A total of 15 compounds were detected in the five time periods. Methylheptenone and phenylethanol were particularly released in the 10:00-12:00 and 15:00-17:00 time periods. There were only three common compounds among the five time periods and the types of flower volatiles released during the daytime were obviously higher than those released at night. From the nocturnal to diurnal, the amount of flower volatiles released first increased, then decreased, and the release reached a peak between 10 am and 12 noon, which was consistent with the pollination biological characteristics of Malus flowers. Our findings are important for understanding the mechanism of insect visits to crabapple and the regulation of crabapple flower scent.


Luminescent cyclometalated platinum(ii) complexes with acyclic diaminocarbene ligands: structural, photophysical and biological properties.
Four new cyclometalated Pt(ii) complexes bearing acyclic diaminocarbene (ADC) ligands, [Pt(C^N)Cl{C(NHXyl)(NHR)}] [C^N = 2,6-difluorophenylpyridine (dfppy), phenylquinoline (pq); R = Pr 3a, 4a, CH2Ph 3b, 4b], were prepared by the nucleophilic attack on the isocyanide [Pt(C^N)Cl(CNXyl)] (C^N = dfppy 1, pq 2) by the corresponding amine RNH2 (R = Pr, CH2Ph). Complexes 3 show in their 1H NMR spectra in CDCl3 a notable concentration dependence, with a clear variation of the δH (NHXyl) signal, suggesting an assembling process implying donor-acceptor NHXylCl bonding, also supported by 1D-PGSE (Pulse Field Gradient Spin Echo) and 2D-DOSY (Diffusion Ordered Spectroscopy) NMR experiments in solution and X-ray diffraction studies. The intermolecular interactions in compounds 3a and 3b were studied by using Hirshfeld surface analysis and Non-Covalent Interaction (NCI) methods on their X-ray structures. Their photophysical properties were investigated by absorption and emission spectroscopies and also by TD-DFT calculations performed on 3a and 4b. These complexes show green (3) or orange (4) phosphorescence, attributed to a mixed 3IL/3MLCT excited state. The carbene ligand does not affect the emission maxima but it produces an increase of the quantum yields in relation to the isocyanide in the precursors. In fluid solutions, the emission is not concentration-dependent, but the complexes may show aggregation induced emission as detailed for complexes 3a and 4a. In addition, cytotoxicity studies in the human cell lines A549 (lung carcinoma) and HeLa (cervix carcinoma) showed good activity for these complexes and 3a, 3b and 4a exhibit a strong effect on DNA electrophoretic mobility. To the best of our knowledge, compounds 3 and 4 represent the first examples of cycloplatinated complexes bearing acyclic diamino carbenes with antiproliferative properties.


The effect of administering multiple doses of tall larkspur (Delphinium barbeyi) to cattle.
Larkspurs ( spp.) are one of the most serious toxic plant problems on foothill and mountain rangelands in the western United States. A considerable amount of research has been conducted over the years in both field and pen settings. The results of these research efforts have significantly increased our understanding of the poisoning of cattle by larkspurs. However, most of the pen studies conducted thus far have used a dosing regimen of a single bolus dose, which does not accurately mimic the manner by which cattle are poisoned by larkspur while grazing. Consequently, the objective of this study was to evaluate the acute toxicity of tall larkspur ( collected near Manti, UT) when administered in multiple doses, with the intent to identify a no observable adverse effect level (NOAEL). The adverse effect selected for this study was muscle weakness to the point the cattle could no longer remain ambulatory as would be required in a grazing environment, thus becoming sternally recumbent when exercised. Hereford steers were administered various doses of tall larkspur at 12-h intervals for 4 d or until they showed marked signs of muscle weakness. The results suggest that a dose of 2 mg kg∙d -(methylsuccinimido) anthranoyllycoctonine (MSAL)-type alkaloids is the NOAEL for a tall larkspur population with a norditerpenoid alkaloid profile containing 4 mg MSAL-type alkaloids/g plant material and 12 mg non-MSAL-type alkaloids/g plant material. Additionally, a computer model was generated to simulate multiple-dosing regimens at the various doses as well as different dosing regimens. The results from this study suggest that a 500-kg steer can consume a daily dose of 1.25 kg of fresh tall larkspur (with a similar alkaloid profile) without becoming severely poisoned (suffering from muscle weakness to the point of recumbency). Additionally, these results indicate that a serum concentration of approximately 355 ng methyllycaconitine/mL may represent a toxic threshold.


Immunohistochemical expression of vascular endothelial growth factor (VEGF) does not correlate with microvessel density in renal cell carcinoma.
The aim of present study was to investigate the relationship between the immunohistochemical expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) assessed by CD31 and endoglin (CD105) in renal cell carcinoma (RCC). Specimens from 45 cases of RCC. were formalin-fixed, paraffin embedded, and sections were stained with H&E. Additional sections from each case were stained for VEGF, CD31, CD105, and alpha smooth muscle cell actin (SMA). VEGF immunohistochemical expression was estimated as negative (0), weak positive (+1), moderate positive (+2), and intense positive (+3). Microvessel density (MVD) was estimated on 5 hot spots (x400) from each case, and the arithmetic media was the final result. MVD was separately calculated on slides stained with CD31 and CD105. The rate between mature and immature blood vessels was calculated on slides stained with CD31/CD105/SMA. Statistic analysis was performed with SPSS10.0. The immunoreaction for VEGF was positive in epithelial cells of the renal tubules, and occasionally, in endothelial cells. In RCC, tumor cells were positive in 34 from 45 cases (75.5%). 11 cases were negative, 14 were slightly positive (+1), 13 moderate (+2), and 7 intense (+3). No relationship was found between the expression of VEGF and pathological form and nuclear grade, excepting for the chromophilic variant (3 cases, all positive). CD31 was positive in all cases, and CD105 in 39 cases. The mean values of MVD on slides stained for CD31 and CD105 were: 31.68 (range 9.8-60.2)/20.66 (range 4.2-52.8). The rate CD31/SMA positive blood vessels was 1/0.62. VEGF was expressed in 75.5% of 45 cases with RCC, and the mean value of MVD CD31/CD105 was 31.68/20.66. The immunohistochemical expression of VEGF does not correlate with MVD performed on slides stained for both CD31 and endoglin. The majority of blood vessels in the tumor area are of mature type, with perivascular cells positive for SMA.


Dense taxonomic EST sampling and its applications for molecular systematics of the Coleoptera (beetles).
Expressed sequence tag (EST) sequences can provide a wealth of data for phylogenetic and genomic studies, but the utility of these resources is restricted by poor taxonomic sampling. Here, we use small EST libraries (<1,000 clones) to generate phylogenetic markers across a broad sample of insects, focusing on the species-rich Coleoptera (beetles). We sequenced over 23,000 ESTs from 34 taxa, which produced 8,728 unique sequences after clustering nonredundant sequences. Between taxa, the sequences could be grouped into 731 gene clusters, with the largest corresponding to mitochondrial DNA transcripts and gene families chymotrypsin, actin, troponin, and tubulin. While levels of paralogy were high in most gene clusters, several midsized clusters including many ribosomal protein (RP) genes appeared to be free of expressed paralogs. To evaluate the utility of EST data for molecular systematics, we curated available transcripts for 66 RP genes from representatives of the major groups of Coleoptera. Using supertree and supermatrix approaches for phylogenetic analysis, the results were consistent with the emerging phylogenetic conclusions about basal relationships in Coleoptera. Numerous small EST libraries from a taxonomically densely sampled lineage can provide a core set of genes that together act as a scaffold in phylogenetic reconstruction, comparative genomics, and studies of gene evolution.


Unfinished feticide: the ethical problems.
Dr. Jansen's paper raises three main issues. The one with which he himself is most concerned is the question of which methods of abortion are ethically right, and whether methods which risk the birth of a damaged baby are wrong. But there are two others: first, how the (originally unintended) birth of a live but damaged child alters the moral situation, and secondly, whether the overcoming of sterility by inducing a multiple pregnancy in which some of the fetuses have to be killed in order for any of them to survive is at all morally acceptable.


Associations between use of cyclosporine-sparing agents and outcome in kidney transplant recipients.
Diltiazem, widely used as a cyclosporine-sparing agent, has been suggested to confer a benefit on graft and patient outcome in kidney transplantation related to immunomodulatory properties. Use of cyclosporine-sparing agents (CsSpA) is routinely recorded by the Australia & New Zealand Dialysis and Transplant (ANZDATA) Registry, and we used these data to examine the associations between CsSpA use and outcomes. Graft and patient survival were analyzed for a cohort of 3913 people who received kidney transplants in Australia or New Zealand between 1 April 1993 and 30 March 2001. Patients were followed to death or loss of graft function. Graft and patient survival analyses were performed using Cox proportional hazards models, including a time varying covariate for CsSpA use in analyses of graft failure. Occurrence of delayed graft function (DGF) and acute rejection also were examined as secondary outcomes. There was no difference in patient survival in the first 12 months post transplantation, but from 12 months onwards there is a survival advantage associated with CsSpA use among cadaveric donor (CD) recipients in both univariate hazard ratio (HR) 0.56, 95% CI 0.41 to 0.76, P < 0.001 and multivariate (HR 0.56, 95% CI 0.40 to 0.79, P < 0.001) analyses. This was consistent across subgroups examined. Lower rates of early graft loss (censored for death) were associated with CsSpA use [odds ratio (OR) 0.61, 95% CI 0.50 to 0.75, P < 0.0001]. Lower rates of use of antibody therapy for rejection also were observed, but not lower rates of biopsy-proven rejection. CsSpA use was associated with improved patient mortality after kidney transplantation. Whether this was a direct drug effect or due to other factors associated with diltiazem use cannot be inferred directly from these data, although several plausible mechanisms exist which might mediate a diltiazem effect.


Connexin-43 redistribution and gap junction activation during forced restraint protects against sudden arrhythmic death in rats.
Connexin-43 (Cx43) expression is reduced or redistributed in heart disease. Restraint or other emotional stressors might cause sudden death in persons with such diseases, but the mechanism of death and its connection to Cx43 during restraint remain unknown. Whether Cx43 distribution or gap junction (GJ) function during restraint is involved in sudden arrhythmic death in rats is addressed in this study. Male Sprague-Dawley rats underwent immobilization (IMO), and individual electrocardiographic responses were monitored by telemetry. Heart sections were used to examine ventricular Cx43 distribution, and GJ intercellular communication (GJIC) activity was assessed using a dye-transfer assay. IMO induced the translocation of Cx43 into to the GJ-rich fraction, with a peak at 60 min. During IMO, Cx43 immunofluorescence was enhanced at intercalated discs, in association with GJIC activation, and premature ventricular contractions (PVCs) increased. In the presence of the GJ inhibitor, carbenoxolone (0.25 mg.kg(-1).h(-1)), IMO induced lethal ventricular tachycardia or fibrillation in 21.7% of rats, in association with QRS prolongation and increased PVCs. IMO causes Cx43 translocation to intercalated discs, thereby reducing vulnerability to lethal arrhythmias via enhancing GJ coupling.


Adult fibrosarcoma of the wrist: a case report.
Adult fibrosarcoma is a rare malignant soft-tissue neoplasm occurring in middle-aged to elderly adults. We present a case of recurrent tumor involving the wrist, which was treated by wide excision including resection of the scaphoid and radio-lunate fusion, followed by coverage of soft tissue defect with a free flap. Despite macro- and microscopic adequate tumor resection, recurrence of the neoplasm occurred at 6 months and eventually amputation of the forearm was performed.


Comparison of response to treatment of unilateral and bilateral varicocelectomy.
We aimed to compare the results of unilateral and bilateral varicocele surgery. In two referral hospitals, the data of 180 patients who were treated with unilateral and bilateral microscopic varicocelectomy were retrospectively analyzed. Sperm parameters and spontaneous pregnancy rates were compared in patients who underwent bilateral and unilateral microscopic varicocelectomy. The mean age was 29.6 (17-46) years. While 82 patients underwent unilateral varicocelectomy (Group I), 98 patients underwent bilaterally varicocelectomy (Group II). Forty (48.8%) spontaneous pregnancies occurred in Group I and 59 (60.2%) in Group II. When we analyzed sperm parameters, the rate of increase in the number of sperm in spermiograms was 17% in Group I and 27.5% in Group II. The rate of increase in sperm mobility was 58.5% and 50% in Group I and II, respectively. The improvement rate in sperm morphology was 46.3% in Group I and 56.1% in Group II. There were no significant differences between all these parameters. In light of our results, although pregnancy rates seemed to be higher in patients who underwent bilateral varicocelectomy, these results were not statistically significant. Improvement rates in sperm parameters were similar between the patients who underwent unilateral and bilateral varicocelectomy.


A Coregistered Ultrasound and Photoacoustic Imaging Protocol for the Transvaginal Imaging of Ovarian Lesions.
Ovarian cancer remains the deadliest of all the gynecological malignancies due to the lack of reliable screening tools for early detection and diagnosis. Photoacoustic imaging or tomography (PAT) is an emerging imaging modality that can provide the total hemoglobin concentration (relative scale, rHbT) and blood oxygen saturation (%sO2) of ovarian/adnexal lesions, which are important parameters for cancer diagnosis. Combined with coregistered ultrasound (US), PAT has demonstrated great potential for detecting ovarian cancers and for accurately diagnosing ovarian lesions for effective risk assessment and the reduction of unnecessary surgeries of benign lesions. However, PAT imaging protocols in clinical applications, to our knowledge, largely vary among different studies. Here, we report a transvaginal ovarian cancer imaging protocol that can be beneficial to other clinical studies, especially those using commercial ultrasound arrays for the detection of photoacoustic signals and standard delay-and-sum beamforming algorithms for imaging.


Esthesioneuroblastoma in children and adolescent: experience on 11 cases with literature review.
Esthesioneuroblastoma is a rare tumor of the olfactory epithelium. This report analyzed 11 children and adolescents treated in a single institution between 1982 and 2002. For 9 patients, therapy consisted of an initial course of chemotherapy before surgical resection and postoperative radiotherapy, for 1 patient an initial course of chemotherapy before radiotherapy and for another resection before radiotherapy with no chemotherapy. Response to chemotherapy was assessed in 9 patients of whom 6 achieved a complete or a partial remission. Ten patients are long-term survivors. The 5-year actuarial disease-free survival and overall survival rate was 91% (95% confidence interval, 62%-98%). Our study indicates that esthesioneuroblastoma is sensitive to chemotherapy and supports the role of combined modalities including neoadjuvant chemotherapy, surgery, and radiation therapy.


Conversion of interferon-induced, long-term cytogenetic remissions in chronic myelogenous leukemia to polymerase chain reaction negativity.
Interferon alfa (IFN-alpha) induces complete cytogenetic remission in a significant minority of patients with chronic myelogenous leukemia (CML). To date, use of the polymerase chain reaction (PCR) has suggested that residual disease is present in virtually all these individuals at median follow-up intervals of approximately 1 year after initial achievement of cytogenetic remission. We sought to determine the PCR status of CML patients with very long continuous complete cytogenetic remissions on IFN-alpha. Blood and/or bone marrow samples from 18 CML patients maintained in continuous cytogenetic remission by IFN-alpha for at least 1 year were studied for residual BCR-ABL mRNA by single-step reverse-transcriptase (RT)-PCR methodology, followed by detection of the amplification product by the hybridization protection assay (HPA). Ten of 18 patients showed RT-PCR negativity for BCR-ABL. The median duration of continuous complete cytogenetic remission at the time of sample collection for the negative patients was 42 months versus 21 months for the patients whose tests remained positive (P = .05). Very long-term follow-up of IFN-alpha-treated CML patients in continuous complete cytogenetic remission is associated with a decrease in the number of BCR-ABL transcripts to a level below that detectable by the RT-PCR assay used in this study.


Fucoxanthin, the constituent of Laminaria japonica, triggers AMPK-mediated cytoprotection and autophagy in hepatocytes under oxidative stress.
Laminaria japonica has frequently been used as a food supplement and drug in traditional oriental medicine. Among the major active constituents responsible for the bioactivities of L. japonica, fucoxanthin (FX) has been considered as a potential antioxidant. This study was conducted to examine the effects of L. japonica extract (LJE) or FX against oxidative stress on hepatocytes and to elucidate the overall their cellular mechanisms of the effects. We constructed an in vitro model with the treatment of arachidonic acid (AA) + iron in HepG2 cells to stimulate the oxidative damage. The cells were pre-treated with LJE or FX for 1 h, and incubated with AA + iron. The effect on oxidative damage and cellular mechanisms of LJE or FX were assessed by cytological examination and several biochemical assays under conditions with or without kinase inhibitiors. LJE or FX pretreatment effectively blocked the pathological changes caused by AA + iron treatment, such as cell death, altered expression of apoptosis-related proteins such as procaspase-3 and poly (ADP-ribose) polymerase, and mitochondria dysfunction. Moreover, FX induced AMPK activation and AMPK inhibitor, compound C, partially reduced the protective effect of FX on mitochondria dysfunction. Consistent with AMPK activation, FX increased the protein levels of autophagic markers (LC3II and beclin-1) and the number of acridine orange stained cells, and decreased the phosphorylation of mTOR and simultaneously increased the phosphorylation of ULK1. And the inhibition of autophagy by 3-methylanine or bafilomycin A1 partially inhibited the protective effect of FX on mitochondria dysfunction. These findings suggest that FX have the function of being a hepatic protectant against oxidative damages through the AMPK pathway for the control of autophagy.


Liver resections for liver transplantations.
Split-Liver and living-related donor liver transplantation are the newest and both technically and ethically most challenging developments in liver transplantation and have contributed to a reduction in donor shortage. We report the technical aspects of surgical procedures performed to achieve a partial graft from a cadaveric and a live donor.


[Acute oral protein administration in the diagnosis of kidney function and causal pathogenetic correlations].
In a literature review it was reported on the performance-orientated diagnostic determination of the glomerular filtration rate by acute oral protein load in man. Recommendations to the standardization of the test realisation are presented. The results of the glomerular filtration reserve--being derived from acute intraindividual changes of the creatinine short-term clearance after an oral protein load--are described in dependence on the renal starting situation. The causal-pathogenetic relations are represented in consideration of the natriuretic hormone and of the pathophysiological model character of the GFR-provocation test to hormonal starting processes, respectively.


Enhancements in healthcare information technology systems: customizing vendor-supplied clinical decision support for a high-risk patient population.
Healthcare organizations continue to adopt information technologies with clinical decision support (CDS) to prevent potential medication-related adverse drug events. End-users who are unfamiliar with certain high-risk patient populations are at an increased risk of unknowingly causing medication errors. The following case describes a heart transplant recipient exposed to supra-therapeutic concentrations of tacrolimus during co-administration of ritonavir as a result of vendor supplied CDS tools that omitted an interaction alert. After review of 4692 potential tacrolimus-based DDIs between 329 different drug pairs supplied by vendor CDS, the severity of 20 DDIs were downgraded and the severity of 62 were upgraded. The need for institution-specific customization of vendor-provided CDS is paramount to ensure avoidance of medication errors. Individualized care will become more important as patient populations and institutions become more specialized. In the future, vendors providing integrated CDS tools must be proactive in developing institution-specific and easily customizable CDS tools.


Biologics for oral corticosteroid-dependent asthma.
Background: Oral corticosteroid (OCS) dependent asthma is one of the severe asthma phenotypes that requires personalized treatment. Objective: To review the role of biologic treatments in OCS-dependent asthma. Methods: A nonsystematic review was performed of emerging multiple novel biologics for potential treatment of OCS-dependent asthma. Results: The serious adverse effects of OCS can be seen as a result of their regular long-term administration. Anti-interleukin (IL) 5 (mepolizumab), anti-IL-5R (benralizumab), and anti-IL-4Rα (dupilumab) are the therapies of choice for OCS-dependent severe asthma. Results of studies showed the efficacy of mepolizumab, benralizumab, and dupilumab, especially in patients with the OCS-dependent severe eosinophilic asthma phenotype and with nasal polyps. Dupilumab may be the therapy of choice of monoclonal antibodies in cases of moderate-severe atopic dermatitis accompanied by OCS-dependent severe asthma. For reslizumab and omalizumab, placebo controlled double-blind studies conducted with OCS-dependent patient populations are needed. Conclusion: Biologics are effective in the "OCS-dependent asthma" phenotype as add-on therapy. It seems that chronic OCS use in OCS-dependent asthma will be replaced by biologic agents that specifically target type 2 inflammation, along with a much better safety profile. However, real-life studies that compare these biologics in OCS-dependent severe asthma are urgently needed.


Differences in Characteristics and Exposure to Stressors Between Persons With and Without Diagnosed Mental Illness Who Died by Suicide in Victoria, Australia.
Background: Mental illness is an established risk factor for suicide. To develop effective prevention interventions and strategies, the demographic characteristics and stressors (other than, or in addition to, mental illness) that can influence a person's decision to die by suicide need to be identified. Aim: To examine cases of suicide by the presence or absence of a diagnosed mental illness (mental illness status) to identify differences in factors associated with suicide in the groups. Method: Logistic regression analyses were used to investigate mental illness status and exposure to stressors among 2,839 persons who died by suicide in Victoria, Australia (2009-2013), using the Victorian Suicide Register. Results: Females, metropolitan residents, persons treated for physical illness/injury, those exposed to stressors related to isolation, family, work, education, and substance use and those who had made a previous suicide attempt had increased odds of having a diagnosed mental illness. Employed persons had decreased odds of having a diagnosed mental illness. Limitations: The retrospectivity of data collection as well as the validity and reliability of some of the data may be questionable owing to the potential for recall bias. Conclusion: The point of intervention for suicide prevention cannot always be a mental health professional; some people who die by suicide either do not have a mental illness or have not sought help.


Mesh migration into stomach following diaphragmatic hernia repair: a rare complication.
Mesh erosion and migration are considered the gravest of complications of mesh repairs. To the best of our knowledge, mesh erosion and migration into the stomach following a mesh repair of adult diaphragmatic hernia has yet to be reported in the literature. A case of mesh eroding into the stomach, after a prosthetic repair of an adult diaphragmatic hernia, is presented here because of its rarity.


Electroconvulsive therapy and memory.
Recent research on the effects of electroconvulsive therapy (ECT) on memory is critically reviewed. Despite some inconsistent findings, unilateral nondominant ECT appears to affect verbal memory less than bilateral ECT. Adequate research on multiple monitored ECT is lacking. With few exceptions, the research methodologies for assessing memory have been inadequate. Many studies have confounded learning with retention, and only very recently has long term memory been adequately studied. Standardized assessment procedures for short term and long term memory are needed, in addition to more sophisticated assessment of memory processes, the duration of memory loss, and qualitative aspects of memories.


Current role and future perspectives of multivariate (chemometric) methods in NMR spectroscopic analysis of pharmaceutical products.
Nuclear magnetic resonance (NMR) is a fast and accurate analytical method. Associated with chemometrics, it gradually becomes more important tool for the pharmaceutical industry. In this review studies dealing with the applications of multivariate analysis to NMR spectroscopic profiles were grouped and discussed according to the analytical problem solved. The following topics were covered: authenticity of medicines according to variety, seasonal and geographical differences of herbal plants; quantitative prediction of pharmacologically relevant parameters; production and batches approval; investigation of drug structure modifications; site-specific natural isotope fractionation (SNIF-NMR) fingerprinting for origin and manufacturer tracking and others. Special focus was put on the heparin authenticity by using 1D and 2D NMR measurements. Finally, further research directions have been outlined. Our review has shown that chemometrics plays an important role for the quality control and authenticity of pharmaceutical products and its role will definitely increase in the future. The discussed approaches are recommended to be implemented during development and production process of pharmaceuticals or in quality control laboratories.


The effect of a low-calorie, high-protein diet on psychometric variables in obese individuals: a Randomized Clinical Trial.
The last decade has seen the increased prevalence of obesity as a public health challenge, particularly in low- and middle-income countries. At the same time, studies have shown that there is a two-way relationship between low-calorie diets and depression in obese individuals. This study was designed and implemented to investigate the effect of a low-calorie high-protein diet on psychometric variables in obese individuals. The present study is a Randomized Clinical Trial. Individuals meeting the inclusion criteria were randomly assigned to either the intervention group (low-calorie diet with increased protein percentage) or the control group (standard protein percentage) using block stratification. Psychometric characteristics of the participants were evaluated using the DASS-21 questionnaire. There were no significant differences in enrollment between the two groups with respect to anthropometric variables, body composition, and physical activity (p-value > .05). Similarly, no significant differences were observed between the two groups in terms of psychological variables (depression, anxiety and stress) (p-value > .05). However, the intervention groups had significantly lower depression and anxiety scores 15 days into the intervention (p-value < .05). After 30 and 60 days of intervention, significant differences were observed between the 2 groups in terms of depression, stress, and anxiety (p-value < .05), indicating a relative improvement in psychometric variables in the intervention group (p-value < .05). The results of this study showed that low-calorie diets with a high-protein percentage can significantly improve psychometric variables in obese people.Trial registration: Iranian Registry of Clinical Trials identifier: IRCT20221101056371N1..


Loading and activation of DNA replicative helicases: the key step of initiation of DNA replication.
Evolution has led to diversification of all living organisms from a common ancestor. Consequently, all living organisms use a common method to duplicate their genetic information and thus pass on their inherited traits to their offspring. To duplicate chromosomal DNA, double-stranded DNA must first be unwound by helicase, which is loaded to replication origins and activated during the DNA replication initiation step. In this review, we discuss the common features of, and differences in, replicative helicases between prokaryotes and eukaryotes.


Displacement of some basic drugs from human serum proteins by enflurane, halothane and their major metabolites. An in vitro study.
The influence of volatile anaesthetics (halothane, enflurane) on the serum protein binding of three highly bound basic drugs has been studied in vitro by equilibrium dialysis. Radioactive labelled isotopes were used for the determination of drug concentrations. Enflurane, halothane and the halothane metabolite trifluoroacetic acid (TFA) inhibited the binding of diazepam to serum and to its main binding protein, albumin. The binding of diazepam to albumin was inhibited in a competitive manner and was not related to the anaesthetic potency of the vapours. Thus the observed displacement of diazepam should be regarded as a side-effect of the volatile anaesthetics. The binding of propranolol and prazosin in serum was not significantly influenced by the investigated anaesthetics. At clinically relevant concentrations of the anaesthetics, diazepam was displaced significantly only by enflurane with an increase in free fraction of 60% in serum. TFA in concentrations seen after operation significantly increased the free fraction of diazepam up to 90%. We conclude that enflurane anaesthesia may temporarily potentiate the pharmacological effect of diazepam and that, in the postoperative period following halothane anaesthesia, a more rapid elimination of diazepam could be expected.


Delays in the diagnosis and treatment of lung cancer.
This study was undertaken to measure delays of diagnosis and to assess the causes for those delays in patients with lung cancer. In addition, the relation of delay times and survival was analyzed. A retrospective study based on patient records. Dates for symptoms, visits to doctors, investigations, treatment, and death were recorded. Patients who were found to have lung cancer at Turku University Hospital, Finland, during 2001. Records of 132 patients were reexamined. The median delay in patient presentation from first symptoms to first appointment with a general practitioner (GP) was 14 days. The median delay by the GP before writing a referral was 16 days, the median referral delay was 8 days, the median delay from the first visit to a specialist until the diagnosis was 15 days, and the median treatment delay was also 15 days. Thirty percent of patients received treatment within 1 month from the first hospital visit, and 61% received treatment within 2 months. The median symptom-to-treatment delay was almost 4 months. The delay in seeing a specialist was shorter in patients with advanced cancer and small cell lung cancer. About half of our patients fulfilled the criteria of the British Thoracic Society recommendations. A longer specialist treatment delay seemed to correlate with better survival in advanced disease, but it was not an independent significant factor for survival. Several reasons for long delays were found, but on many occasions patients underwent numerous consecutive procedures before a diagnosis of cancer was confirmed. Shortening the diagnostic and treatment delay times might be possible with little extra cost by a multidisciplinary team approach and by rapid access to carefully planned investigations, but decreasing the patient delay might be more difficult. This study shows that long specialist treatment delays are not correlated with worse prognosis in patients with advanced disease. In patients with more limited disease, the delay time may be more critical, and if curative treatment is the goal, the diagnostic process should proceed without needless delay to avoid a situation in which curable disease becomes incurable.


Proton distribution in Sc-doped BaZrO3: a solid state NMR and first principle calculations analysis.
Perovskite-based material Sc-doped BaZrO3 is a promising protonic conductor but with substantially lower conductivities than its Y-doped counterpart. 1H solid-state NMR spectroscopy in combination with DFT modelling was used to analyze the protonic distribution in BaZr1-xScxO3-x/2-y(OH)2y and its effect on charge carrier mobility. 1H single pulse and 1H-45Sc TRAPDOR MAS NMR experiments highlighted the mobile character of the proton charge carriers at room temperature, giving rise to a single broad resonance, protons hopping between multiple sites on the NMR timescale. At low temperatures, the protonic motion was successfully slowed down allowing direct observation of the various proton environments present in the structure. For x ≤ 0.15, DFT modelling suggested a tendency for strong dopant-proton association leading to Sc-OH-Zr environments with 1H NMR shifts of 4.8 ppm. The Zr-OH-Zr environment, H-bonded to a Sc-O-Zr, lies 32 kJ mol-1 higher in energy than the Sc-OH-Zr environment, suggesting that the Sc-OH-Zr environment is trapped. However, even at these low concentrations, Sc-Sc clustering could not be ruled out as additional proton environments with stronger 1H-45Sc dipolar couplings were observed (at 4.2 and 2.8 ppm). For x = 0.25, DFT modelling on the dry material predicted that Sc-□-Sc environments were extremely stable, again highlighting the likelihood of dopant clustering. A large number of possible configurations exists in the hydrated material, giving rise to a large distribution in 1H chemical shifts and multiple conduction pathways. The 1H shift was found to be strongly related to the length of the O-H bond and, in turn, to the hydrogen bonding and OOH distances. The breadth of the NMR signal observed at low temperature for x = 0.30 indicated a large range of different OH environments, those with lower shifts being generally closer to more than one Sc dopant. Lower DFT energy structures were generally associated with weaker H-bonding environments. Both the calculations and the DFT modelling indicated that the protons tend to strongly bond to the Sc clusters, which, in conjunction with the higher energies of configurations containing Zr-OH-Zr groups, could help explain the lower conductivities recorded for the Sc-substituted BaZrO3 in comparison to its yttrium counterpart.


LncRNA LINC01270 aggravates the progression of gastric cancer through modulation of miR-326/EFNA3 axis.
Gastric cancer (GC) is lethal malignancy, which is associated with high mortality. Long noncoding RNA LINC01270 has been identified to act as a potential oncogene in several cancers. However, its role and related regulatory mechanism in GC are yet to be illustrated. The levels of lncRNA LINC01270, miR-326, and EphrinA3 (EFNA3) were assessed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) and colony formation assays were applied for analyzing cell proliferation. Transwell assay was used for measuring cellular migration and invasion. Western blot analysis was employed for evaluating the protein levels. Luciferase reporter and RNA pull-down assays were utilized to verify the binding ability between LINC01270 (or EFNA3) and miR-326. Our findings indicated that LINC01270 expression was significantly up-regulated in GC tissues and cell lines. Additionally, LINC01270 knockdown attenuated GC progression through inhibiting cell proliferation, migration, and invasion. Functional experiments identified that lncRNA LINC01270 could positively regulate EFNA3 expression by serving as a competing endogenous RNA (ceRNA) for miR-326. Through rescue assays, inhibition of GC progression caused by LINC01270 suppression was found to be reversed by the application of miR-326 inhibitor or EFNA3 overexpression. Overall, our work demonstrated that lncRNA LINC01270 can accelerate cell proliferation, migration, and invasion via modulating miR-326/EFNA3 axis. These findings might implicate the potential role of lncRNA LINC01270 in GC treatment.


Reduction of Tomato-Plant Chilling Tolerance by CRISPR-Cas9-Mediated SlCBF1 Mutagenesis.
Chilling stress is the main constraint in tomato ( Solanum lycopersicum) production, as this is a chilling-sensitive horticultural crop. The highly conserved C-repeat binding factors (CBFs) are cold-response-system components found in many species. In this study, we generated slcbf1 mutants using the CRISPR-Cas9 system and investigated the role of SlCBF1 in tomato-plant chilling tolerances. The slcbf1 mutants exhibited more severe chilling-injury symptoms with higher electrolyte leakage and malondialdehyde levels than wild-type (WT) plants. Additionally, slcbf1 mutants showed lower proline and protein contents and higher hydrogen peroxide contents and activities of antioxidant enzymes than WT plants. Knockout of SlCBF1 significantly increased indole acetic acid contents but decreased methyl jasmonate, abscisic acid, and zeatin riboside contents. The reduced chilling tolerance of the slcbf1 mutants was further reflected by the down-regulation of CBF-related genes. These results contribute to a better understanding of the molecular basis underlying SlCBF1 mediation of tomato chilling sensitivity.


Increased history of childhood and lifetime traumatic events among adults with alopecia areata.
Whether adult alopecia areata (AA) is associated with childhood or total lifetime traumatic events is not known. Previous studies have investigated only the relationship with recent stressful events. We sought to determine whether patients with AA experience more childhood or total lifetime traumatic events, as measured by the Traumatic Experiences Checklist. Using a case-control study, data on 90 patients with AA and 91 control subjects were analyzed. Significantly more patients with AA experienced total lifetime and early childhood traumatic events, with an odds ratio of 2.46 (95% confidence interval 1.15-5.28; P = .017) and 2.16 (1.15-4.06; P = .016), respectively. In patients with AA, the global impact score related to their traumatic experiences was significantly higher than in control subjects (P < .001). In addition, patients with AA experienced significantly more emotionally and physically traumatic events. This case-control study is susceptible to recall bias and to confounding factors associated with stress caused by AA outbreaks or by a traumatic childhood history. Our study documents an increased history of childhood trauma in patients with AA compared with control subjects.


Perceptual and Semantic Representations at Encoding Contribute to True and False Recognition of Objects.
When encoding new episodic memories, visual and semantic processing is proposed to make distinct contributions to accurate memory and memory distortions. Here, we used fMRI and preregistered representational similarity analysis to uncover the representations that predict true and false recognition of unfamiliar objects. Two semantic models captured coarse-grained taxonomic categories and specific object features, respectively, while two perceptual models embodied low-level visual properties. Twenty-eight female and male participants encoded images of objects during fMRI scanning, and later had to discriminate studied objects from similar lures and novel objects in a recognition memory test. Both perceptual and semantic models predicted true memory. When studied objects were later identified correctly, neural patterns corresponded to low-level visual representations of these object images in the early visual cortex, lingual, and fusiform gyri. In a similar fashion, alignment of neural patterns with fine-grained semantic feature representations in the fusiform gyrus also predicted true recognition. However, emphasis on coarser taxonomic representations predicted forgetting more anteriorly in the anterior ventral temporal cortex, left inferior frontal gyrus and, in an exploratory analysis, left perirhinal cortex. In contrast, false recognition of similar lure objects was associated with weaker visual analysis posteriorly in early visual and left occipitotemporal cortex. The results implicate multiple perceptual and semantic representations in successful memory encoding and suggest that fine-grained semantic as well as visual analysis contributes to accurate later recognition, while processing visual image detail is critical for avoiding false recognition errors.SIGNIFICANCE STATEMENT People are able to store detailed memories of many similar objects. We offer new insights into the encoding of these specific memories by combining fMRI with explicit models of how image properties and object knowledge are represented in the brain. When people processed fine-grained visual properties in occipital and posterior temporal cortex, they were more likely to recognize the objects later and less likely to falsely recognize similar objects. In contrast, while object-specific feature representations in fusiform gyrus predicted accurate memory, coarse-grained categorical representations in frontal and temporal regions predicted forgetting. The data provide the first direct tests of theoretical assumptions about encoding true and false memories, suggesting that semantic representations contribute to specific memories as well as errors.


The Potential Prognostic Significance of the Laboratory Risk Indicator for the Necrotizing Fasciitis (LRINEC) Score in Necrotizing Fasciitis.
Background: We discuss the role of Laboratory Risk Indicator for the Necrotizing Fasciitis (LRINEC) on the prognosis of this disease. Necrotizing Fasciitis (NF) is characterised by rapid spreading of infection and necrosis of the soft tissues and fascia. Methods: Thirty patients (17 male, 13 female, mean age 57.5 years) were treated between 2011- 2016 (in our center); they were analysed retrospectively regarding age, sex, isolated microbiological agents, modalities of treatment and mortality rate. Results: The majority of the infections were detected in the perineum (14 patients). Other sites of infection were: the presacral region (3 patients), as well as abdominal region after elective (10 patients) and emergency surgery (2 patients), respectively. 53.3% of patients had at least one predisposing comorbid factor such as diabetes mellitus, hypertension, cardiomyopathy and congestive heart failure. The tissue cultures were positive in 12 patients. Mean LRINEC score on admission was 8.5 +-2.85. There was a strong correlation between LRINEC score and patient age (p=0.018, R=0.43). LRINEC score was affected by neither gender nor the presence of any comorbidities. The patients were classified according to Wang and Wong staging system, as follows: one patient in stage 1, 15 patients in stage 2 and 14 patients in stage 3. Patients with higher Wang and Wong stages had significantly higher LRINEC scores. The mortality rate was 16.7%. The mean LRINEC score of deceased patients compared to patients who were successfully treated was 9.2Â+-2.2 and 8.36Â+-2.9. Conclusion: Even though LRINEC score and Wang and Wong stage were significatly related with ICU stay, their direct effect on mortality wasn't significant in our study.


Evaluation of the cadmium phytoextraction potential of tobacco (Nicotiana tabacum) and rhizosphere micro-characteristics under different cadmium levels.
In this study, a field-scale and pot experiment were performed to evaluate the remedial efficiency of Cd contaminated soil by tobacco and explore rhizosphere micro-characteristics under different cadmium levels, respectively. The results indicated that tobacco could remove 12.9 % of Cd from soil within a short growing period of 80 d. The pot experiment revealed that tobacco could tolerate soil Cd concentrations up to 5.8 mg kg-1 and bioaccumulate 68.1 and 40.8 mg kg-1 Cd in shoots and roots, respectively. The high Cd bioaccumulation in tobacco might be attributed to strong acidification in the rhizosphere soil and the increase in Cd bioavailability. Rhizobacteria did not appear to be involved in Cd mobilization. In contrast, tobacco tended to enrich sulfate-reducing bacteria (such as Desulfarculaceae) under high Cd treatment (5.8 mg kg-1) but enrich plant growth-promoting bacteria (such as Bacillus, Dyadobacter, Virgibacillus and Lysobacter) to improve growth under low Cd treatment (0.2 mg kg-1), suggesting that tobacco employed different microbes for responding to Cd stress. Our results demonstrate the advantages of using tobacco for bioremediating Cd contaminated soil and clarify the rhizosphere mechanisms underlying Cd mobilization and tolerance.


Traces of experience in the lateral entorhinal cortex.
A growing body of evidence suggests that memories are stored in the hippocampus by integrating spatial information from specialized cell types in the medial entorhinal cortex (MEC) with nonspatial information from cells in the lateral entorhinal cortex (LEC). LEC neurons show little spatial modulation when rats run in empty open-field environments but fire in the vicinity of discrete objects, suggesting that they provide information about the specific content of the spatial environment. It is unclear, however, whether firing at objects is elicited purely by stimulus properties, in a sensory-like manner, or whether any higher-order property, such as the history of experience, is also relevant. To address this question, we recorded from LEC neurons in an open field where objects were present on a subset of the trials. Whereas some neurons fired at the objects, other cells developed specific firing at places where objects had been located on previous trials, providing a readout of past experience in the environment. The latter cells generally did not respond to the object when it was present, suggesting that object cells and object-trace cells are independent cell classes. These findings identify LEC as a component of the hippocampal-cortical circuit for object-place memory.


Digitization in the insurance sector - challenges in the face of the Covid-19 pandemic.
The Covid-19 crisis has accelerated the need for a digital transformation of insurance companies, which has shifted from being a strategic option to a necessity. Dynamic changes are transforming the insurance sector. Insurance market leaders who look boldly into the future have not resorted to observation alone and they take actions that allow them to be more customer-oriented, improve their offers, and increase operational efficiency. The aim of this article is to present the digitization processes taking place in the insurance sector in the face of the crisis caused by the Covid-19 pandemic and an attempt to answer the following research question: has digitization in the insurance sector taken the right direction and is a response to the needs of the insurance market participants (insurers, insured persons, intermediaries, etc.) as a consequence of the actual epidemic risk (Covid-19) and its consequences. In order to verify the research question and achieve the set goal, a critical analysis of the source literature, the analysis of trends and digital solutions in the insurance sector and the analysis of secondary data were performed. The study was based on data available in national and international reports, including data published by the Polish Insurance Association, OECD or the Geneva Association. The presented results of the considerations indicate that the use of new technologies and ubiquitous digitization have a great impact on customer expectations, which was particularly noticeable in the aftermath of the epidemic risk come true (Covid-19). The article highlights the changes introduced in the organization's processes (the importance of decision support systems in insurance activities), as well as supporting consumer users (the universality of social media, and the availability of speech and image recognition technology).


Clinicopathological analysis of cervical cancer seen in a tertiary health facility in Nnewi, south-east Nigeria.
Cervical cancer remains the commonest gynaecological cancer among women in the developing countries. The records of all the histologically confirmed cervical cancer patients managed in Nnamdi Azikiwe University Teaching Hospital, Nnewi, over a 5 year period were analysed for the clinical presentation and histological pattern of the malignancy. A total of 75 cases of cervical cancer were managed over the period giving an incidence of 65.2% of all gynaecological cancers and 13.4% of all gynaecological admissions. The majority of the patients were grandmultiparous women (81.3%) with a mean parity of 6.8. The modal age range was 60-69 years (38.7%) and the majority (94.7%) of the patients belonged to the low socioeconomic class. Squamous cell carcinoma of varying differentiation (89.3%) was the commonest histological type seen and adenocarcinoma accounted for only 8.0%. The common clinical features were post-menopausal bleeding (84.0%), vaginal discharge (72.0%), contact bleeding (63.9%) and abdominal pain (56.2%). Most (89.3%) of the patients presented late, in advanced stages of the disease, and almost all (97.3%) were referred for radiotherapy. The incidence of cervical cancer is high in our environment. Community sensitisation and provision of free cervical screening is recommended for early detection and treatment.


Synthesis of pyrrolo[2,1-a]isoquinolines by multicomponent 1,3-dipolar cycloaddition.
Pyrrolo[2,1-a]isoquinoline derivatives were synthesized by one-pot three-component reactions starting from isoquinoline, 2-bromoacetophenones and different non-symmetrical acetylenic dipolarophiles using 1,2-epoxypropane as solvent. The structure of the compounds was assigned by IR and NMR spectroscopy.


Effect of non-surgical periodontal therapy on insulin resistance in patients with type II diabetes mellitus and chronic periodontitis, as assessed by C-peptide and the Homeostasis Assessment Index.
A bidirectional relationship exists between diabetes and periodontitis. In the present clinical trial, we evaluated the effects of non-surgical periodontal therapy (NSPT) on insulin resistance in patients with type II diabetes mellitus (DM) and chronic periodontitis. Forty chronic periodontitis patients with type II DM were selected and equally allocated to case and control groups. All patients were assessed for periodontal parameters and systemic parameters. The case group received NSPT, and both groups were re-evaluated after 3 months. All periodontal parameters were found to be significantly improved in the case group compared to the control group 3 months after NSPT. The mean differences in systemic parameters, such as fasting serum C-peptide, Homeostasis Assessment (HOMA) Index-insulin resistance, and HOMA-insulin sensitivity, from baseline to 3 months for the case group were 0.544 ± 0.73, 0.54 ± 0.63, and -25.44 ± 36.81, respectively; for the control group, they were significant at -1.66 ± 1.89, -1.48 ± 1.86, and 31.42 ± 38.82 respectively (P < 0.05). There was a significant decrease in fasting blood glucose and glycosylated hemoglobin A1c from baseline to 3 months in the case group (P < 0.05). The present study showed that periodontal inflammation could affect glycemic control and insulin resistance. Effective periodontal therapy reduced insulin resistance and improved periodontal health status and insulin sensitivity in patients with type II DM and chronic periodontitis.


[Soybean bacteriological culture media and prospects for their use in clinical bacteriology].
Agar bacteriological nutrient media are suggested, based on soybean extract subjected to enzymatic hydrolysis and lyophilized native. The growth of test strains, number of grown colonies and their size were virtually the same as after inoculation of these strains in control nutrient media. Soybean salt medium with yolk suspension was tried with good results as elective medium for isolation of staphylococci from clinical material. Commercial manufacture of these media mainly from native soybean extract is proposed.


Skin graft coverage of critical marginal wounds in microsurgical cases.
Skin graft coverage of critical marginal wounds in microsurgical cases is the earliest described method for coverage of exposed vessels, nerves, and other vital structures at the margins of replanted or transplanted tissue. A case of immediate graft coverage of vein and nerve graft repairs in a gunshot wound is presented with a 5-year follow-up demonstrating stable coverage, salvage of the microsurgical reconstruction, and no contracture. Compared to recently described strategies of interval biosynthetic dressings and delayed skin grafting, immediate skin grafts application remains the most effective management of these wounds.


How can gynaecologists cope with the silent killer - osteoporosis?
Osteoporosis is a very common disease among women. It is frequently called a silent epidemic and, due to its impact on osteoporotic fractures with high morbidity and mortality, also a silent killer. There are a number of significant risk factors for osteoporosis, some of them very strongly related to the functioning of the reproductive system. These include menstrual irregularities, premature ovarian failure, early natural or surgical menopause, a high number of pregnancies, and long-term breast-feeding. Hence, there is every reason to include gynaecologists in the multidisciplinary team striving to cope with this dreadful disease. Calculation of the 10-year fracture risk, done by means of the FRAX calculator, and classification of women according to the level of risk could prove to be an effective method of limiting the negative effects of osteoporosis.


Inhibition of Ligand-Gated TRPA1 by General Anesthetics.
Several general anesthetics (GAs) produce pain or irritation upon administration, and this occurs predominantly through the activation of the nociceptive ion channel, transient receptor potential ankyrin type 1 (TRPA1). However, the effects of GAs on agonist-mediated TRPA1 activity are unclear. Here we show that a diverse range of noxious and non-noxious volatile anesthetics, at clinically relevant concentrations, inhibit ligand-activated TRPA1 currents. These effects are species-specific; GAs blocks rodent TRPA1 without affecting the Drosophila ortholog. Furthermore, propofol inhibits rodent but not human TRPA1. Analysis of chimeric TRPA1 proteins and mutagenesis combined reveals two amino acid residues located in the S5 domain, Ser876 and Thr877, that are critical for the inhibitory effects of isoflurane and propofol. Introduction of these residues into Drosophila TRPA1 confers anesthetic inhibition. Furthermore, several residues lining the presumptive binding pocket for noxious GAs are not required for the inhibitory effects of GAs. We conclude that anesthetics inhibit TRPA1 by interacting at a site distinct from the activation site. The inhibitory effects of GAs at TRPA1 may contribute to the diverse pharmacological action of these drugs. SIGNIFICANCE STATEMENT: We show that both noxious and non-noxious general anesthetics inhibit agonist-evoked transient receptor potential ankyrin type 1 (TRPA1) activity and identify critical amino acid residues located in the pore domain. Inhibition of TRPA1 may affect pain and vascular signaling during anesthesia.


Identification of GZMA as a Potential Therapeutic Target Involved in Immune Infiltration in Breast Cancer by Integrated Bioinformatical Analysis.
Granzyme A (GZMA) is a potential prognostic target for various cancer types. However, its therapeutic significance in breast cancer with immune infiltration remains controversial. We analyzed GZMA expression and its prognostic value in breast cancer with immune cell infiltration. Data was obtained from patients with breast cancer registered at The Cancer Genome Atlas. A correlation was performed between GZMA expression and patient's clinicopathological features such as age, pathologic stage, metastasis stage, overall survival (OS), disease-specific survival (DSS), and progress free interval (PFI). Kaplan-Meier analyses and Cox proportional hazard regression model were used to examine the predictive significance of GZMA expression for breast cancer. The co-expression pattern of GZMA was assessed by the LinkedOmics web portal. The relationship between GZMA expression and immune cells was analyzed using the TIMER database. The correlation between GZMA and lymphocytes and immunomodulators was established with the TISIDB database. There was a lower GZMA expression in breast cancer tissue than in normal tissue. Interestingly, GZMA expression was associated with age, pathologic stage, and the Tumour, Node, and Metastasis stage. Overexpression of GZMA was also associated with better OS, DSS, and PFI. Based on the Cox regression analysis, GZMA was identified as an independent favorable prognostic factor for breast cancer. Our findings demonstrated a strong association between GZMA and T-cell checkpoints (PD-1, PD-L1, and cytotoxic T lymphocyte-associated antigen (CTLA-4)) in breast cancer. Moreover, we evaluated the interactions between GZMA expression and markers of dendritic and CD8+ T cells using quantitative immunofluorescence. We discovered that increased infiltration of dendritic and CD8+ T cells was associated with GZMA expression in breast cancer. GZMA expression is associated with a favorable prognosis in breast cancer and is significantly correlated with immune cell infiltration. GZMA may be considered a promising therapeutic target for patients with breast cancer.


Nutritional status and insecticide tolerance in German cockroaches (Orthoptera: Blattellidae).
The interrelationship of two extrinsic factors-nutrition and pesticide exposure-was studied in German cockroaches, Blattella germanica (L.). Amount of dietary protein had no effect on susceptibility of male German cockroaches to propoxur and chlorpyrifos; however, the source of protein produced significant changes in insecticide susceptibility. Increased total body lipids, carbohydrates, and uric acid may have resulted in increased tolerance to these insecticides. Three days of food or water deprivation (or both) caused significant differences in susceptibility to chlorpyrifos and propoxur.


Changes in T-lymphocyte subpopulations and natural killer cells following exposure to ambient levels of nitrogen dioxide.
The effects of ambient levels of NO2 on murine splenic T-lymphocyte subpopulations and natural killer cells were investigated. AKR/cum and C57BL/6J mice were exposed, in inhalation chambers, to 0.25 ppm NO2 for 7 wk and 0.35 ppm NO2 for 12 wk, respectively. Monoclonal antibody technology was used in conjunction with fluorescence-activated cell sorter (FACS) analysis to detect quantitative changes in total T-lymphocytes (Thy-1.2-positive), mature T-lymphocytes (Lyt-1-positive), T-helper/inducer lymphocytes (L3T4-positive), T-cytotoxic/suppressor lymphocytes (Lyt-2-positive), and natural killer cells (asialo GM1-positive). Percentages of all T-lymphocyte subpopulations tested and natural killer cells were lower in spleens of mice exposed to NO2 compared to filtered-air controls. This is the first report providing evidence linking alterations in T-lymphocyte subpopulations and natural killer cells to NO2 exposure at ambient levels. Changes in T-lymphocyte subpopulations detected by FACS and correlated to impaired immune function may provide an extremely sensitive means of demonstrating NO2-induced changes in the immune system.


Fostering interprofessional collaboration through a family-centred programme for grandparent-headed families.
Interprofessional education (IPE) is now widely considered an essential part of preparing professionals to work more effectively with marginalised families, such as grandparent-headed families. This study aims to explore the potential for IPE through a family-centred programme for grandparent-headed families during professional preparation for education, social work, and nursing students to foster collaboration. Using mixed methods with concurrent data collection and analyses, this study suggests that participation in IPE can positively impact perceptions of interprofessional collaboration to better meet the multifaceted needs of grandparent-headed families by increasing awareness and self-efficacy for interprofessional collaboration in schools and deepening understandings of non-traditional families. Implications highlight possibilities for more flexible and integrated professional identities in working with children and their families as well as the potential for future school professionals to embrace more comprehensive services in schools.


Hypermethylation of the GRHL2 promoter region is associated with ovarian endometriosis.
Abnormal gene expression caused by epigenetic changes, including DNA methylation, is associated with the development and progression of endometriosis. Grainyhead-like 2 gene (GRHL2), a suppressor of epithelial-mesenchymal transition, has been suggested to be associated with the occurrence, progression and poor survival of a variety of cancers. Although endometriosis is a benign disease, it has the biological behaviour of migration and invasion as malignant tumor. This study aims to determine whether the abnormal expression of the GRHL2 caused by aberrant methylation of its promoter is associated with the pathogenesis of ovarian endometriosis. Our results demonstrated that GRHL2 promoter region was significantly hypermethylated in the ectopic endometrium of patients with ovarian endometriosis compared with the normal endometrium of control patients. In contrast, the levels of GRHL2 mRNA and protein were significantly lower in the ectopic endometrium than in the control endometrium. Correlation analysis showed the methylation levels of GRHL2 were significantly negatively correlated with the mRNA expression of GRHL2. Moreover, the in vitro results suggested that the knockdown of GRHL2 could significantly increase the invasion and migration ability of EECs and may promote ZEB1 and vimentin expression while decreasing the expression of E-cadherin in EECs. Taken together, these results suggest that the low expression of GRHL2 caused by hypermethylation of the GRHL2 promoter is associated with ovarian endometriosis. The knockdown of GRHL2 may be involved in the occurrence of endometriosis by increasing EEC migration and invasion. This study provides more evidence for the hypothesis that endometriosis may be an epigenetic regulatory disorder.


Potentiation of vasopressin secretion by footshocks in rats.
Effects of footshocks (FS) on antidiuretic hormone (vasopressin, VP) in the plasma were studied in rats. Continuously applied FS of 60 s period with 5 ms pulses at 50 Hz frequency significantly increased VP as well as adrenocorticotrophic hormone (ACTH) in the plasma in a time- and shock intensity-dependent manner. Contrarily, the 50 Hz FS of 2 s period as repeated intermittently at every 15 s for over the period of 2, 10, and 30 min were much less effective for increasing plasma VP, whereas these intermittent FS increased plasma ACTH to an extremely high level. During the inter-shock intervals of 13 s between successive two shock periods rats exhibited a "freezing" behavior. Hypertonic saline or urethane injected I.P. immediately after termination of the intermittent FS significantly increased VP as well as ACTH in the plasma. These data clearly indicate that FS potentiate VP secretion and suggest the possibility that emotional stress may suppress the noxious stimuli-induced VP secretion.


The growth of Propionibacterium cyclohexanicum in fruit juices and its survival following elevated temperature treatments.
This study investigated the growth of Propionibacterium cyclohexanicum in orange juice over a temperature range from 4 to 40 degrees C and its ability to multiply in tomato, grapefruit, apple, pineapple and cranberry juices at 30 and 35 degrees C. Survival after 10 min exposure to 50, 60, 70, 80, 85, 90 and 95 degrees C in culture medium and in orange juice was also assessed. In orange juice the organism was able to multiply by 2 logs at temperatures from 4 to 35 degrees C and survived for up to 52 days. However, at 40 degrees C viable counts were reduced after 6 days and no viable cells isolated after 17 days. The optimum growth temperature in orange juice over 6 days was 25 degrees C but over 4 days it was 35 degrees C. The growth of P. cyclohexanicum was monitored in tomato, grapefruit, cranberry, pineapple and apple juices at 30 and 35 degrees C over 29 days. Cranberry, grapefruit and apple juice did not support the growth of P. cyclohexanicum. At 30 degrees C no viable cells were detected after 8 days in cranberry juice or after 22 days in grapefruit juice while at 35 degrees C no viable cells were detected after 5 and 15 days, respectively. However, in apple juice, although a 5 log reduction occurred, viable cells could be detected after 29 days. P. cyclohexanicum was able to multiply in both tomato and pineapple juices. In tomato juice, there was a 2 log increase in viable counts after 8 days at 30 degrees C but no increase at 35 degrees C, while in pineapple juice there was a 1 log increase in numbers over 29 days with no significant difference between numbers of viable cells present at 30 and 35 degrees C. The organism survived at 50 degrees C for 10 min in culture medium without a significant loss of viability while similar treatment at 60, 70 and 80 degrees C resulted in approximately a 3-4 log reduction, with no viable cells detected after treatment at 85 or 90 or 95 degrees C but, when pre-treated at intermediate temperatures before exposure to higher temperatures, some cells survived. However, in orange juice a proportion of cells survived at 95 degrees C for 10 min without pre-treatment and there was no significant difference between numbers surviving with and without pre-treatment. The results from this study demonstrate that P. cyclohexanicum is able to grow in a number of juices, other than orange juice, and able to survive a number of high temperature procedures. Therefore, if initially present in the raw materials P. cyclohexanicum might survive the pasteurization procedures used in the fruit juice industry, contaminate and consequently spoil the final product.


The relationship between oxygen permeability and phase separation morphology of the multicomponent silicone hydrogels.
In this article, the multicomponent copolymers were prepared by the copolymerization of two hydrophobic silicon-containing monomers bis(trimethylsilyloxy) methylsilylpropyl glycerol methacrylate (SiMA) and tris(trimethylsiloxy)-3-methacryloxypropylsilane (TRIS) with three hydrophilic monomers 2-hydroxyethyl methacrylate, N-vinylpyrrolidone, and N,N-dimethyl acrylamide. The copolymers were hydrated to form transparent silicone hydrogels. The oxygen permeability coefficients (Dk) of hydrogels were measured, and their relationships with the equilibrium water contents (EWC) and the types and contents of silicon containing monomers as well as the phase separation structures of silicone hydrogels were analyzed in detail. The results showed that the EWC decreased as the increase of SiMA content. The relationship between Dk and SiMA content, as well as that between Dk and EWC, showed inverted bell curve distributions, which meant two main factors, i.e., silicon-oxygen bond in silicone and water in hydrogel, contributed to oxygen permeation and followed a mutual inhibition competition mechanism. The internal morphologies of the hydrogels were observed by transmission electron microscope, and the results showed that the hydrogels presented two different phase separation structures depending on the types of the silicon-containing monomers. The silicone phase in SiMA containing hydrogel presented to be a granular texture, while the silicone phase in TRIS containing hydrogel formed a fibrous texture which resulted in a higher Dk value. These results could help to design a silicone hydrogel with better properties and wider application.


Specific targeting of antisense oligonucleotides to neutrophils.
The ability of three different hydrophobic ligands (cholic acid, cholesterol, and the tetrapeptide fMLFY) to increase the uptake of an antisense (anti-actin) oligomer into neutrophils was analyzed. In agreement with the literature (Boutorin et al., 1989; Letsinger et al., 1989), we found that cholic acid and cholesterol conjugates greatly enhance the uptake of anti-actin oligomer. When fMLFY is the ligand, the cellular uptake is much less than that of anti-actin oligomer alone, but the biological consequences are much more significant. Our results are consistent with the hypothesis that the fMLFY conjugate of the anti-actin oligomer is internalized via a different route, and reaches its target site most efficiently.


Raw water clarification by flotation with microbubbles and nanobubbles generated with a multiphase pump.
Raw water clarification by flotation was studied by injecting air into a centrifugal multiphase pump to generate microbubbles (MBs) and nanobubbles (NBs). Measurements of gas dispersion parameters were performed and optimal conditions were obtained using a pump pressure of 4 bar. Values showed a bubble Sauter diameter of 75 μm, an air holdup of 1.2%, a bubble surface area flux of 34 s-1 and an NB concentration of 1 × 108 NBs mL-1 (measuring 220 nm). Then, a study compared flotation with bubbles formed with the multiphase pump (F-MP) to lamellar settling at the clarification stage of a water treatment plant (WTP), in Brazil. The F-MP showed a higher separation efficiency at high hydraulic loads (9-15 m h-1), even without the use of a polymer, reaching 2 NTU (10-25 NTU raw water feed), which was much lower than the technical goal of the WTP (5 NTU). The results and the technical aspects are discussed, and it is concluded that the employment of MBs and NBs with pumps widens new research lines and applications in modern flotation.


Application of direct thermal desorption gas chromatography and comprehensive two-dimensional gas chromatography coupled to time of flight mass spectrometry for analysis of organic compounds in ambient aerosol particles.
Semivolatile organic compounds (SVOC) associated with ambient particles smaller than 2.5 microm (PM2.5) were determined in the city of Augsburg, Germany. Daily samples were collected at a central monitoring station from late summer 2002 to spring 2005. SVOC were analysed by direct thermal desorption (DTD)-GC and comprehensive 2-D GC coupled to TOF MS (DTD-GC-TOF MS and DTD-GC x GC-TOF MS). Two hundred compounds were quantified and 'semi-quantified' on a daily basis by DTD-GC-TOF MS. n-Alkanes, n-alkan-2-ones, n-alkanoic acid methyl esters, acetic acid esters, n-alkanoic acid amides, nitriles, linear alkylbenzenes and 2-alkyl-toluenes, hopanes, PAH, alkylated PAH and oxidised PAH, and several compounds that are not-grouped in homologous rows or compound classes were determined. Changes in concentration and pattern of several target compounds as well as methodological advantages and restrictions of DTD-GC-TOF MS are briefly discussed. DTD-GC-TOF MS analysis provided data particularly suited for source receptor modelling and epidemiological time series studies on the health effects of ambient PM. GC x GC enhances chromatographic resolution of PM samples and therefore amplifies the peak identification capabilities of the TOF MS.


Morphologic and histochemical characteristics of the dental cuticle in teeth affected by prepubertal periodontitis.
A study was undertaken to determine the nature and composition of the cuticle found in teeth with generalized prepubertal periodontitis (PP). This was accomplished by using histological and histochemical methods on decalcified specimens. Forty-six permanent teeth which were extracted from three prepubertal periodontitis patients (siblings) were used. Nineteen of the 46 teeth were obtained with the facial or interdental gingiva. As a control, 20 healthy teeth extracted from 10 children for orthodontics reasons, and 22 teeth affected by terminal adult periodontitis (AP), were used. All the teeth with PP showed a thick coat covering the root surface from the cemento-enamel junction to the junctional epithelium. In some teeth the cuticle extended a few microns coronally to the cemento-enamel junction. The cuticle had a thickness which varied between 10 to 80 microns. It usually presented a very regular surface in the coronal portion of the root, and showed laminations suggesting appositional growth. In the middle and apical portions of the root exposed to the pocket, the cuticle was lobular with a very irregular surface and was covered with a thick microbial plaque. The staining reactions indicated that the cuticle was made of proteins probably derived from the inflammatory exudate. None of the healthy teeth examined nor those affected by AP showed a cuticle similar to those with PP. The cuticle formed on the teeth with PP appears to be an abnormal structure of proteinaceous nature, characteristic of these teeth, and may possibly play a role in the pathogenesis of the disease.


Neonatal dengue: an under-diagnosed entity.
Neonatal dengue is an under-diagnosed disease likely due to low index of suspicion along with its resemblance to sepsis. We hereby report two cases of neonatal dengue, highlighting the need of high degree of suspicion in infants born to febrile mothers even with maternal serology being negative. Moreover, severity of neonatal illness positively correlates with the maternal disease.


Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
Congenital disorders of glycosylation (CDG) represent a group of inherited multiorgan diseases caused by defects in the biosynthesis of glycoproteins. We report on two dysmorphic siblings with severe liver disease who died at the age of a few weeks. Increased activities of lysosomal enzymes in plasma were found, though total sialic acid in plasma was strongly decreased. Isoelectric focusing of serum sialotransferrins showed a type 2-like CDG pattern. Some of the known CDG subtypes were excluded. O-Glycosylation was investigated by isoelectric focusing of apolipoprotein C-III, which showed increased fractions of hyposialylated isoforms. In a consecutive study a defect in the conserved oligomeric Golgi complex was established at the level of subunit COG-7, leading to disruption of multiple glycosylation functions of the Golgi. This report on patients with a new variant of CDG, due to a multiple Golgi defect, emphasizes in addition to sialotransferrins the importance of analysis of a serum O-linked glycoprotein, e.g. apolipoprotein C-III, in unclassified CDG-X cases.


Pancreas graft drainage in recipient duodenum: preliminary experience.
Pancreas graft survival has continuously improved over the years to become a main treatment option of uncontrolled complicated diabetes. Rejection remains the major challenge as it often goes unnoticed until severe damage of the graft manifests itself by elevated blood sugar. Pancreas enzymes monitoring in the blood and in the urine is a sensitive marker of rejection but lack of specificity. Biopsy remains the gold standard. Cystoscopy-guided biopsy of bladder-drained pancreas has a good success rate for obtaining tissue but the vesical drainage exposes to metabolic and urologic morbidity. Percutaneous pancreas biopsy can be performed with a low morbidity rate but severe complications can occur. We discuss a technique of pancreas transplantation with the drainage of exocrine secretions of the pancreatic graft in the recipient duodenum, which permits easy monitoring of the graft by upper endoscopy of the duodenum.


[The use of intravascular hypothermia to correct intracranial hypertension in patients with severe traumatic brain injury].
Assess to impact hypothermia on ABP, CPP, ICP and cerebral autoregulation. Material and methods. 14 patients with TBI (GOS<9) underwent hypothermia by Thermogard system within 32-35 °C (Zoll, USA). ICP was measured intraparenchymal by Codman sensor. Cerebral autoregulation was estimated by correlation coefficient Prx (Soft ICM Plus, Cambridge, UK). Temperature was measured in urinary bladder. There were selected five time periods: 1 - phase of initial state, 2 - phase of induction hypothermia, 3 - phase of hypothermia, 4 - phase of rewarming, 5 - phase after finishing hypothermia. All data preset as Mediana (min; max). Stat analysis was perfomed using Soft Statistica 10.0. Results. Phase 1 lasted nearly 7 (2; 12) h, ABP 94 (81; 102), CPP - 73 (52; 87), ICP 27 (16; 45) mm Hg, Prx 0,25 (-0,15; 0,7), temperature 38,2 °C (37; 39,8). Phase 2: 5 (2; 12) h, ABP 95 (85; 114), CPP 80 (65; 96), ICP 18 (10; 22) mm Hg, Prx -0,055 (-0,15; 0,7), temperature 35,2 °C (34,5; 35,5). Phase 3: 55 (20; 100) h, there were not significant changed ABP, CPP, Prx, ICP 15 (10; 18) mm Hg, temperature was 33,5 °C (32; 34,7). Phase 4: 17 (8; 24) h, ABP 90 (70; 100), CPP 77 (55; 85), ICP 15 (9; 27) mm Hg and Prx 0,2 (-0,2; 0,32). Temperature 36,9 °C (35,9; 38,5). Phase 5: 20 (6; 240) h, ABP 87(53; 110), CPP 72 (47; 107), ICP 17 (10; 32) mm Hg and Prx 0,2 (-0,2; 0,6). Temperature 37,7 °C (36,7; 39,0). Conclusion. Hypothermia is an effective method for correction of intracranial hypertension. Hypothermia can use as a additional option of intensive care during refractory intracranial hypertension. Rewarming phase is the most dangerous time on the re-development of intracranial hypertension and disruption of autoregulation.


Low voltage FE-STEM for characterization of state-of-the-art silicon SRAM.
Low voltage (30 kV) field emission scanning transmission electron microscopy (FE-STEM) has been employed in the characterization of state-of-the-art semiconductor static random access memory (SRAM) using specimens prepared at several different thicknesses (70-180 nm). A focused ion beam (FIB) system, a FIB-SEM compatible specimen holder and an in-lens FE-SEM have been employed for alternating between FIB milling and SEM/ STEM imaging. As a result, ion implanted atom damage during manufacturing, grains in aluminium interconnects, poly silicon gates, thin metal barriers and a thin gate oxide layer were observed by low voltage FE-STEM. STEM, in-lens FESEM, FIB


Isolated prostatic metastasis from primary sigmoid colon carcinoma.
Metastasis to the prostate is extremely uncommon. We report a 38-year-old man with sigmoid colon carcinoma, treated with surgery and adjuvant chemotherapy, who developed isolated metastasis to the prostate four years after initial treatment. He was treated with chemoradiation and remains disease-free three years after detection of metastasis.


Clinical pharmacokinetic interactions between antiepileptic drugs and hormonal contraceptives.
Contraceptive management in women with epilepsy is critical owing to the potential maternal and fetal risks if contraception or seizure management fails. This article briefly describes the pharmacokinetic interactions between antiepileptic drugs (AEDs) and hormonal contraceptives and the rational strategies that may overcome these risks. Hormonal contraception, including the use of oral contraceptives (OCs), is widely used in many women with epilepsy - there is no strong evidence of seizures worsening with their use. AEDs are the mainstay for seizure control in women with epilepsy. However, there are many factors to consider in the choice of AED therapy and hormonal contraception, since some AEDs can reduce the efficacy of OCs owing to pharmacokinetic interactions. Estrogens and progestogens are metabolized by cytochrome P450 3A4. AEDs, such as phenytoin, phenobarbital, carbamazepine, felbamate, topiramate, oxcarbazepine and primidone, induce cytochrome P450 3A4, leading to enhanced metabolism of either or both the estrogenic and progestogenic component of OCs, thereby reducing their efficacy in preventing pregnancy. OCs can also decrease the concentrations of AEDs such as lamotrigine and, thereby, increase the risk of seizures. Increased awareness of AED interactions may help optimize seizure therapy in women with epilepsy.


Pharmaconutrition with selenium in critically ill patients: what do we know?
Selenium is a component of selenoproteins with antioxidant, anti-inflammatory, and immunomodulatory properties. Systemic inflammatory response syndrome (SIRS), multiorgan dysfunction (MOD), and multiorgan failure (MOF) are associated with an early reduction in plasma selenium and glutathione peroxidase activity (GPx), and both parameters correlate inversely with the severity of illness and outcomes. Several randomized clinical trials (RCTs) evaluated selenium therapy as monotherapy or in antioxidant cocktails in intensive care unit (ICU) patient populations, and more recently several meta-analyses suggested benefits with selenium therapy in the most seriously ill patients. However, the largest RCT on pharmaconutrition with glutamine and antioxidants, the REducing Deaths due to Oxidative Stress (REDOXS) Study, was unable to find any improvement in clinical outcomes with antioxidants provided by the enteral and parenteral route and suggested harm in patients with renal dysfunction. Subsequently, the MetaPlus study demonstrated increased mortality in medical patients when provided extra glutamine and selenium enterally. The treatment effect of selenium may be dependent on the dose, the route of administration, and whether administered with other nutrients and the patient population studied. Currently, there are few small studies evaluating the pharmacokinetic profile of intravenous (IV) selenium in SIRS, and therefore more data are necessary, particularly in patients with MOD, including those with renal dysfunction. According to current knowledge, high-dose pentahydrate sodium selenite could be given as an IV bolus injection (1000-2000 µg), which causes transient pro-oxidant, cytotoxic, and anti-inflammatory effects, and then followed by a continuous infusion of 1000-1600 µg/d for up to 10-14 days. Nonetheless, the optimum dose and efficacy still remain controversial and need to be definitively established.


Color gamut of a nematic liquid crystal display under ambient illumination.
The theoretical color gamut of a nematic liquid crystal display under ambient illumination is described. The color gamut in the transmission-type of both the tunable-birefringence and guest-host modes is shown by the CIE chromaticity diagram and color solid. Calculation of the color matching between the given chromaticity coordinates and those calculated at the variable lightness of the ambient illumination was executed by the matrix representation method. Calculated data for ambient illumination having the same chromaticity as the reference illumination are in good agreement with the colorimetric data within a tolerable color difference in the 1964 CIE (U*,V*,W*) color scale.


Action representations activated by task-irrelevant information: is it really irrelevant?
Accessing action knowledge is believed to rely on the activation of action representations through the retrieval of functional, manipulative, and spatial information associated with objects. However, it remains unclear whether action representations can be activated in this way when the object information is irrelevant to the current judgment. The present study investigated this question by independently manipulating the correctness of three types of action-related information: the functional relation between the two objects, the grip applied to the objects, and the orientation of the objects. In each of three tasks in Experiment 1, participants evaluated the correctness of only one of the three information types (function, grip or orientation). Similar results were achieved with all three tasks: "correct" judgments were facilitated when the other dimensions were correct; however, "incorrect" judgments were facilitated when the other two dimensions were both correct and also when they were both incorrect. In Experiment 2, when participants attended to an action-irrelevant feature (object color), there was no interaction between function, grip, and orientation. These results clearly indicate that action representations can be activated by retrieval of functional, manipulative, and spatial knowledge about objects, even though this is task-irrelevant information.


Prognostic significance of cytogenetic abnormalities in patients with chronic myelogenous leukemia.
The cytogenetic data for 126 patients with Ph-positive chronic myelogenous leukemia (CML) in accelerated phase or blast crisis were analysed for clonal chromosomal abnormalities in addition to the standard Ph prior to allogeneic or syngeneic bone marrow transplantation (BMT). Additional clonal abnormalities were found in 84%, and 14% had a variant Ph (VPh). In decreasing order of frequency, the most common clonal abnormalities were a second Ph, +8, i(17q), -Y and +19. A second Ph, VPh or +8 occurred more frequently in patients who relapsed following BMT than in those who survived disease-free for at least 1 1/2 years. The presence of an i(17q) alone did not correlate with relapse. The patients with a second Ph, VPh or +8 had a median time to relapse of 19 months, and the risk of relapse at 3 years was 73%. Those with other or no additional clonal abnormalities had not reached a median time to relapse and had a 3-year risk of relapse of 31% (p = 0.002). This analysis suggests that specific cytogenetic abnormalities may be useful indicators of resistance to therapy for CML and should be included in proportional hazard models to predict outcome after BMT.