Cyberbullying: a 21st Century Health Care Phenomenon.
This study examined bullying and cyberbullying prevalence among 367 adolescents 10 to 18 years of age who were attending schools and community organizations in suburban and urban neighborhoods in the Midwest United States. The correlational design investigated adolescents' daily use of technology that could be used to cyberbully peers, such as cell phones, computers, email, and the Internet. Results showed that 30% of participants had been bullied during school, and 17% had been cyberbullied, with online social networking sites the most common media employed (68%). The majority of participants owned or had access to computers (92%), email accounts (88%), social networking accounts (e.g., Facebook or MySpace) (82%), and cell phones (79%). Daily technology use included an average of two hours on a computer and a median of 71 text messages per day. Logistic regression analysis revealed no significant differences in bullying or cyberbullying prevalence based on location (urban or suburban) or demographic characteristics. Given the substantial presence of cyberbullying and the increase in technology use among adolescents in the 21st century, nurses need knowledge of the phenomenon to plan assessments in clinical practice. Early identification and assessment of cyberbullying victims and perpetrators, and development and implementation of effective interventions are needed to reduce this form of bullying among adolescents.


Method for measuring mean particle size of the bulk powder using speckle patterns.
We report a method for measuring the mean size of fine particles in a bulk state using the correlation properties of two speckle patterns. With this method, the correlation between the two speckle patterns produced from the same region of the upper surface of the powder bed under two coherent illuminations is measured using double-exposure speckle photography and a cross-correlated method. It is found to be directly related to the surface-area mean diameter of particles over the bed surface and the incidence angle difference between two illuminations. This technique has the advantage of simplicity in the measuring procedure, including the pretreatment of the sample powder.


[Clinical significance of studies of microorganisms of the intestinal mucosa by culture biochemical methods and mass fragmentography].
This research is a continuation of the series of studies of the parietal microbiota of the bowel tissue samplings by the gas chromatography and mass spectrometry (GCMS) method [G.A. Ossipov et al.//Journal of the Society of Russian Gastroenterologists, 2001, 1:54-69]. The purpose was to study a number of new microorganisms in view of new data on the composition of their fatty acids (FA) and aldehydes; to confirm the presence of a number of bacteria, fungi and aerobic actinomycetes revealed earlier by FA markers in the composition of the bowel parietal microbiota by their isolation in a pure culture; to amend the estimation of the clinical value of changes in the composition of the human bowel parietal microflora in case of irritable bowel syndrome (IBS) and antibiotics-associated diarrhea (AAD). We examined 31 patients with IBS with predominating diarrhea, 18 patients with AAD and 3 volunteers (a control group). We studied the blood samples, tissue samplings of the mucous coat of the jejunum, ileum and colon and composition of healthy people's feces. The GCMS method was applied. Morphology of defined strains was controlled by methods of light and scanning electron microscopy. We found a substantial portion of eubacteria among the bowel microorganisms and specific changes of their species in case of IBS and AAD. Taking into account their physiological and biochemical activity, when regulating their concentration one can expect at least the same effect as when regulating the number of bifidobacteria and lactobacilli in treatment of intestinal pathologies and other diseases related to bowel dysbacteriosis. The analysis of the feces microbiota using the GCMS method by FA of parietal microorganisms provides reliable data on their number both in feces and in tissue samplings. We found a substantial portion of eubacteria among other bowel microorganisms (27% in the jejunum and 16% in the colon) and specific changes of their species in case of IBS and AAD. The concentration of streptomycetes, rhodococci and other members of the Actinomycetales order becomes dozens times more and/or reduces in pathological states. The tenfold concentration of markers of lactobacilli and bifidobacteria in some diseases stimulates the differentiated application of widespread probiotics based on these bacteria.


Making steady progress on direct cardiac reprogramming toward clinical application.
A new report demonstrates direct cardiac reprogramming in human cells for the first time and points to the possibility of moving this technology toward clinical applications.


The association between BMI and COPD: the results of two population-based studies in Guangzhou, China.
An association between chronic obstructive pulmonary disease (COPD) and low body mass index (BMI) has been well established in cross-sectional studies. However, there have been few cohort studies investigating this issue. We therefore aimed to address this gap. Two population-based studies, a cross-sectional study including 1818 subjects and a subsequent 4-year cohort study consisting of 759 individuals without COPD, were conducted in Guangzhou, China. Every subject was 40 years old or older at the time of recruitment and completed questionnaire interviews, anthropometric measurements and spirometry testing. As a follow-up, each subject underwent annual pre-bronchodilator spirometry testing. Subjects with a pre-bronchodilator FEV1/FVC <0.7 were required to undergo post-bronchodilator spirometry testing. Subjects with a post-bronchodilator FEV1/FVC <0.7 were diagnosed with COPD. Compared to subjects with normal BMI (18.5 to 23.9 kg/m(2)), those with low BMI (<18.5 kg/m(2)) had a higher prevalence of COPD (21.1% vs. 7.5%), with an adjusted OR of 2.75 [95% confidence intervals (CI): 1.69 to 4.47]. Both low BMI and obese (≥ 28.0 kg/m(2)) subjects had lower FEV1 after adjustment. This association was further confirmed in the cohort study; non-COPD subjects with low BMI at baseline were more likely to develop COPD (RR = 2.88, 95% CI: 1.06 to 7.85), independent of smoking status and other confounders. Low BMI was not only a systemic consequence of COPD but also an important risk factor for the development of COPD, which raises the possibility that early intervention in subjects with low BMI may reduce the incidence of COPD.


Klotho reduces apoptosis in experimental ischaemic acute renal failure.
Klotho is associated with the suppression of several ageing phenotypes. Because high klotho gene expression was detected in the kidney and several studies have found altered expression in animal models, we explored the physiological relevance of klotho expression in the kidney under renal ischemia reperfusion injury (IRI). Male Wistar rats were subjected to bilateral renal ischemia or sham operation, followed by reperfusion for 6, 12 or 24 h, or 2 to 10 days. Renal expression of klotho was assessed by real-time PCR or Western blotting. Creatinine levels were determined. Immunohistochemical studies and TUNEL staining were performed. An adenovirus harbouring the mouse klotho gene (ad-kl) was intravenously administered to one group of rats before renal IRI. Renal klotho mRNA and protein expressions were significantly reduced in IRI rats the first day after ischemia. Pre-treatment with ad-kl resulted in a robust induction of klotho mRNA and protein in the liver but not in the kidney. Ad-kl gene transfer improved serum creatinine and the histological changes. Apoptosis induced by IRI was attenuated following ad-kl administration. The data suggest klotho to be involved in the pathophysiology of IRI. Downregulation of renal klotho exacerbates ischaemic acute renal failure, and klotho gene induction has therapeutic potential in managing ischaemic renal damage.


Management of extramammary Paget's disease with a staged, modified Mohs technique.
Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma arising from apocrine glands. We describe an innovative surgical technique to manage extensive cutaneous malignancies in a notoriously challenging location. The patient is a 78-year-old male who presented with 'jock itch' on his left groin refractory to topical treatment. A shave biopsy of the lesion demonstrated non-invasive EMPD which yielded a urology consult. Rather than the standard wide local excision (WLE), which can lead to positive margins, progression, and recurrence, we used a modified the Mohs technique and staged the procedure, providing excellent oncologic and cosmetic outcomes. The described technique has particular merit with uncertain margin status and when geography of lesions preclude a standard Mohs surgery.


Long-term safety and effectiveness of high-dose dimethylfumarate in the treatment of moderate to severe psoriasis: a prospective single-blinded follow-up study.
Mixtures of fumaric acid esters (FAE) are used as an oral systemic treatment for moderate to severe psoriasis. Large clinical studies with dimethylfumarate (DMF) monotherapy are scarce. The objective of this study is to assess the effectiveness and long-term safety of high-dose DMF monotherapy in moderate to severe psoriasis. A prospective single-blinded follow-up study was performed in a cohort of patients treated with DMF. Patients were followed-up at fixed intervals. Assessment of consecutive photographs was performed by two observers. Primary outcome was a change in static physician global assessment (PGA) score. Safety outcome was defined as incidences of (serious) adverse events. A total of 176 patients with moderate to severe psoriasis were treated with DMF for a median duration of 28 months. The median daily maintenance dosage of 480 mg was reached after a median of 8 months. Psoriasis activity decreased significantly by 1.7 out of five points. A total of 152 patients reported one or more adverse events, such as gastrointestinal complaints and flushing. High-dose DMF monotherapy is an effective and safe treatment option in moderate to severe psoriasis. It can be suggested that 50% of all patients may benefit from high-dose DMF monotherapy.


Imaging of Intracellular Hydrogen Peroxide Production with HyPer upon Stimulation of HeLa Cells with EGF.
Reactive oxygen species (ROS) regulate both normal cell functions by activating a number of enzymatic cascades and pathological processes in many diseases by inducing oxidative stress. For many years since the discovery of ROS in biological systems there were no adequate methods of detection and quantification of these molecules inside the living cells. We developed the first genetically encoded fluorescent indicator for intracellular detection of hydrogen peroxide, HyPer, that can be used for imaging of H2O2 production by cells under various physiological and pathological conditions. Unlike most known ROS indicators, HyPer allows for the generation of real-time image series that give precise information about the time course and intensity of H2O2 changes in any compartment of interest. In this chapter we describe the method of confocal imaging of hydrogen peroxide production in HeLa cells upon stimulation with epidermal growth factor. The technique described may be accepted with minimal variations for the use in other cell lines upon various conditions leading to H2O2 production.


Congenital ichthyosiform erythroderma (C.I.E.)--ultrastructural evidences of abnormal stratum corneum retention.
Congenital ichthyosiform erythroderma (C.I.E.) is a skin disorder which has been considered as a hyperkinetic hyperkeratosis. This study was performed in order to demonstrate that C.I.E. pathogenesis includes both basal cell hyperplasia and abnormal stratum corneum retention. Electron microscopic studies were carried out on 5 cases of C.I.E., clinically and histopathologically diagnosed. The following pathological changes were found in stratum corneum and stratum granulosum: persistence of desmosomes in outer layers of stratum corneum, increased volume of intercorneocyte material, loss of lamellar pattern of Odland bodies, important variability in size and shape of keratohyaline granules, abnormal aggregation of tonofilaments. These constitute ultrastructural evidences of abnormal stratum corneum retention in C.I.E. pathogenesis.


SMART Cougars: Development and Feasibility of a Campus-based HIV Prevention Intervention.
University campuses are promising sites for service implementation because they have the infrastructure to support services, offer access to an otherwise difficult to reach population, and prioritize knowledge sharing among all entities. As HIV rates continue to rise among minority young adults, the need to implement innovative programs at the university level also increases. The University of Houston's (UH) Substance Use, Mental Health, and HIV/AIDS Risk Assessment and Testing (SMART Cougars) program provides HIV testing and education, mental health, and substance abuse services and referrals to students on campus and in surrounding communities. The aim of this paper is to describe development and examine feasibility of SMART Cougars (SC). Using Bowen's feasibility framework, we found that SC produced a demand, was acceptable and appropriate, implemented without many challenges, and integrated among university and community settings. Combined, these factors and processes changed social norms around sexual health messages on campus.


A threshold exists in the dose-response relationship for somatic mutation frequency induced by X irradiation of Drosophila.
The dose-response relationship of ionizing radiation and its stochastic effects has been thought to be linear without any thresholds. The basic data for this model were obtained from mutational assays in the male germ cells of the fruit fly Drosophila melanogaster. However, it is more appropriate to examine carcinogenic activity in somatic cells than in germ cells. Here the dose-response relationship of X irradiation and somatic mutation was examined in Drosophila. A threshold at approximately 1 Gy was observed in DNA repair-proficient flies. In the repair-deficient siblings, the threshold was smaller and the inclination of the dose-response curve was much steeper. These results suggest that the dose-response relationship between X irradiation and somatic mutation has a threshold and that the DNA repair function contributes to its formation.


Phosphorylation of the nuclear transport machinery down-regulates nuclear protein import in vitro.
We have examined whether signal-mediated nucleocytoplasmic transport can be regulated by phosphorylation of the nuclear transport machinery. Using digitonin-permeabilized cell assays to measure nuclear import and export, we found that the phosphatase inhibitors okadaic acid and microcystin inhibit transport mediated by the import receptors importin beta and transportin, but not by the export receptor CRM1. Several lines of evidence, including the finding that transport inhibition is partially reversed by the broad specificity protein kinase inhibitor staurosporine, indicate that transport inhibition is due to elevated phosphorylation of a component of the nuclear transport machinery. The kinases and phosphatases involved in this regulation are present in the permeabilized cells. A phosphorylation-sensitive component of the nuclear transport machinery also is present in permeabilized cells and is most likely a component of the nuclear pore complex. Substrate binding by the importin alpha.beta complex and the association of the complex with the nucleoporins Nup358/RanBP2 and Nup153 are not affected by phosphatase inhibitors, suggesting that transport inhibition by protein phosphorylation does not involve these steps. These results suggest that cells have mechanisms to negatively regulate entire nuclear transport pathways, thus providing a means to globally control cellular activity through effects on nucleocytoplasmic trafficking.


Optic neuropathy associated with laser in situ keratomileusis.
To report 4 cases of optic neuropathy following laser in situ keratomileusis (LASIK). Tertiary Care ophthalmic practices. In this retrospective observational case series, 4 patients who developed acute visual loss following LASIK are reported. All had clinical evidence of optic neuropathy. Two had optic disc edema and 2 had normal appearing optic discs initially. None of the patients experienced significant visual recovery, and all developed optic atrophy in the affected eye. All patients had evaluations for alternative etiologies of their optic neuropathy, with negative results. All patients were therefore presumed to have experienced an ischemic optic neuropathy following LASIK. Patients who have LASIK may experience an acute anterior or retrobulbar optic neuropathy. The etiology is unknown but may be related to the marked increase in intraocular pressure that occurs during a portion of the procedure.


Listeria monocytogenes endophthalmitis: a case report.
Listeria monocytogenes endophthalmitis is characterised by a progressively darkening indolent hypopyon. Gentamicin and amoxycillin, as used in this, the first reported Australian case, is the currently recommended treatment.


Visual disturbance as initial presentation of hairy cell leukemia.
Hairy cell leukemia (HCL) is a rare disorder that occasionally has visual symptoms after diagnosis. The authors present a case of HCL in which bilateral visual symptoms led to the initial diagnosis. Observational case report. Bilateral decreased vision to 20/30 in the right eye and 20/40 in the left due to intraretinal and preretinal hemorrhages with no other systemic signs or symptoms prompted a hematologic evaluation in which HCL was found to be the causative disorder in a previously healthy 41-year-old man. The authors present a rare case in which bilateral visual complaints led to the diagnosis of HCL. Thus, though uncommon, HCL should be considered in the differential diagnosis of otherwise unexplained retinal hemorrhages.


Pharmacological inhibition of salivary glands: a possible therapy for sialosis and sialoadenitis. Effect of experimentally induced beta-receptor block on the rat parotid gland.
An increase of alpha-amylase concentration and specific amylase activity (correlated to protein content) was evident already after 3 days in the parotid glands of rats treated with 2 X 2 mg/day of propranolol hydrochloride. After separation of amylase into isoenzymes, only the specific isoamylase activities were enhanced. In contrast to treatment with a guanethidine derivative (guanoxane), these changes have persisted after 3 weeks. On the strength of these results, functional inhibition of the salivary glands (i.e. blockade of secretion by beta-sympatholytic agnets) is discussed as a therapeutical possibility for the management of sialosis and sialoadenitis.


[Expression and immunity reaction of a novel gene OmpL17 of the strong virulent L. interrogans serovar Lai in China].
This study was conducted to potentiate the expression of outer membrane protein OmpL17 of the strong virulent L. interrogans serovar Lai and investigate its immunogenicity in rabbits. The OmpL17 was cloned into prokaryotic expression vector pGEX-1lambdaT. The recombination expression plasmid pGEX-OmpL17 was transformed into E. Coli JM109. The GST fused protein GST-OmpL17 was expressed after induction by IPTG, then GST-tag was by thrombin and purified using Bulk GST purification Modules. SDS-PAGE and Western blotting analysis indicated that the molecular weight of GST-OmpL17 and OmpL17 was about 54 KDa and 28 KDa respectively. The outer membrane protein OmpL17 was subcutaneously injected into rabbits and high titre anti-OmpL17 antibody was obtained (1:4896) which could conjugate specifical with OmpL17. In conclusion, OmpL17 and specifical anti-OmpL17 antibody were obtained, which provided an experimental basis for researching pathogenic effect and immunity functions of OmpL17.


Baclofen in treatment of the 'stiff-man' syndrome.
A 36-year-old diabetic man with the stiff-man syndrome previously treated with diazepam improved dramatically when baclofen was added to the regimen. Cyclobenzaprine had no therapeutic effect.


Bisphenol A and estrone-induced developmental effects in early chick embryos.
Endocrine disruptors, especially estrogenic substances, are thought to affect the reproduction and development of animals, including humans. We therefore assessed whether bisphenol A (BPA) or estrone (E1) had any adverse effects on chick embryogenesis. Fertilized eggs of white Leghorns were obtained within 24 h after laying. Embryos were administered 0.1, 1.0, and 10.0 mM BPA, and administered 10, 100 nM, and 1 μM E1, and incubated for 48 h at 37 ± 0.5°C and >80% relative humidity with one rotation per hour. The embryos were excised, fixed in 70% ethanol and viewed under a stereomicroscope. Their morphological abnormalities and numbers of somites were recorded. There were no significant difference in the average number of somites in embryos administered BPA and controls. Abnormal embryogenesis, however, showed dose-related increases caused by BPA and E1.


The effect of intracuff alkalinized 2% lidocaine on emergence coughing, sore throat, and hoarseness in smokers.
We evaluated whether endotracheal tube (ETT) intracuff alkalinized lidocaine was superior to saline in blunting emergence coughing, postoperative sore throat, and hoarseness in smokers. In our prospective, double-blind trial, we enrolled 50 smoking patients undergoing surgery under general anesthesia including nitrous oxide (N2O). Patients were randomly allocated to receive either ETT intracuff 2% lidocaine plus 8.4% sodium bicarbonate (L group), or ETT intracuff 0.9% saline (S group). The ETT cuff was inflated to achieve a cuff pressure that prevented air leak during positive pressure ventilation. Incidence of emergence coughing, sore throat, and hoarseness were analyzed. The volume of inflation solution, the intracuff pressure, the duration of anesthesia, the time elapsed to extubation after discontinuation of anesthesia, and the volume of the inflation solution and the air withdrawn from the ETT cuff were also recorded. Intracuff alkalinized 2% lidocaine was superior to saline in blunting emergence coughing (p < 0.001). The incidence of sore throat was significantly lower in the L group at the post-anesthesia care unit (PACU) (p = 0.02). However, at 24 hours after extubation, sore throat incidence was similar in both groups (p = 0.07). Incidence of hoarseness was similar in both groups. Intracuff pressure in the saline group increased with time while the intracuff pressure in the lidocaine group remained constant. The present study demonstrated that the intracuff alkalinized 2% lidocaine was superior to saline in decreasing the incidence of emergence coughing and sore throat during the postoperative period in smokers.


[Production of primary cells cultures by a semi-industrial technic. II. Use of active trypsin solutions for effective cell yields].
For effective cell yields in semi-industrial production of primary cell suspensions, the use of trypsin solutions with high enzyme activity has been proved to be an essential requirement. Enzyme solutions with a constant high activity may be obtained by using an optimal filtration method. Filtration results using the deep and membrane filtration method to sterilize trypsin solutions are demonstrated and discussed. A number of trypsin samples taken from the "Leidholdt-Firm" were tested concerning cell yields in the so-called 'Biomix-Procedure'. A correlation could be shown to exist between enzyme activity and cell yield. The so tested trypsin-L-samples out of the years 1976/78 were proved to be first-rate preparations for routine production of primary piglet and calf kidney cell cultures.


Acute and long-term clinical significance of myocardial contusion following blunt thoracic trauma: results of a prospective study.
The clinical significance of myocardial contusion (MC) following blunt thoracic trauma is still unknown. Accordingly, in this prospective study in a regional trauma center we investigated the acute and long-term clinical significance of MC. One-hundred eighteen patients with manifest or suspected blunt thoracic trauma were evaluated for cardiac injury. Initial assessment was based on results of electrocardiographic, echocardiographic, and serial enzyme measurements. A follow-up (FU) assessment conducted at 3 and 12 months, respectively, was performed using electrocardiography, echocardiography, and a bicycle ergometry exercise test. Of the 118 patients in the total sample, 67 (56.8%) required admission to the surgical intensive care unit (SICU) because of the severity of their noncardiac injuries. Fourteen patients of the total sample (11.8%) were diagnosed with MC and 13 of these (92.9%) belonged to the intensive care admissions, thus representing an incidence of 19.4% in this patient group. During the hospitalization period none of the patients with MC experienced acute cardiac complications. Eighty-six patients (72.0%) were assessed at FU. No new pathologies were found except in one patient. Exercise testing revealed no ECG abnormalities and none of the patients experienced limitations on the bicycle ergometer due to a cardiac cause. The incidence of 19.7% of MC in our patients with blunt chest injury requiring intensive care treatment indicates that this condition is frequent in polytraumatized patients. Outcome and prognosis in patients with MC is favorable and, thus, routine cardiac work-up is not indicated. Specific diagnostic and therapeutic measures should be limited to cases where cardiac complications develop.


Acetylene as a substrate in the development of primordial bacterial communities.
The fermentation of atmospheric acetylene by anaerobic bacteria is proposed as the basis of a primordial heterotrophic food chain. The accumulation of fermentation products (acetaldehyde, ethanol, acetate and hydrogen) would create niches for sulfate-respiring bacteria as well as methanogens. Formation of acetylene-free environments in soils and sediments would also alter the function of nitrogenase from detoxification to nitrogen-fixation. The possibility of an acetylene-based anaerobic food chain in Jovian-type atmospheres is discussed.


The results of improved cementing techniques for total hip arthroplasty in patients less than fifty years old. A ten-year follow-up study.
Thirty-six patients (forty-two hips) in whom so-called second-generation cementing techniques, such as medullary lavage, use of an intramedullary cement plug, hand-mixing of the cement, and use of a cement gun to deliver the cement in a doughy state in a retrograde fashion, had been used for a primary total hip arthroplasty were evaluated at an average of eleven years (range, ten to fifteen years) after the operation. All of the patients had been less than fifty years old at the time of the operation. Thirty-one patients were evaluated by clinical and radiographic examinations and five, by a telephone interview. Twelve components (ten acetabular components [24 per cent] and two femoral components [5 per cent]) in ten hips had been revised for aseptic loosening. An additional five acetabular components (12 per cent) and five femoral components were definitely loose according to radiographic criteria. Three of these femoral components were polished stems that were considered loose only because of the presence of a radiolucent line, 0.5, one, and two millimeters wide, at the prosthesis-cement interface in zone 1 of Gruen et al. The other two loose stems were in patients who were receiving renal dialysis. These findings demonstrate excellent fixation of the femoral component but continued problems with fixation of the acetabular component despite the use of improved cementing techniques.


Investigating the Barons: narrative and nomenclature in Munchausen syndrome.
Recounting stories of the 18th-century Baron von Münchhausen, the unauthorized appropriation of his name into literature, and Richard Asher's subsequent medical use of the name Munchausen 150 years later, this article examines the narratives that are told about and through Munchausen syndrome that create meaning within medicine. By analyzing a half-century debate over the name of the illness, this article discusses how the medical literature invests meaning in names and how names create meaning through narrative with effects on the practice of medicine.


Lifesavers and Samaritans: emergency use of cellular (mobile) phones in Australia.
There has been highly publicised concern about possible radiation health effects from mobile phones and towers, but scant attention has been paid to the use of mobile phones in reducing notification times in emergencies. National random telephone survey of Australian mobile phone users (n = 720) and extrapolation to national user population (n = 5.1 million). Using a cellular phone, 1 in 8 users have reported a traffic accident; 1 in 4 a dangerous situation; 1 in 16 a non-road medical emergency; 1 in 20 a crime; and 1 in 45 being lost in the bush or being in difficulty at sea. Any debate about the net health impact of mobile phone proliferation must balance possible negative effects (cancer, driving incidents) with the benefits from what appears to be their widespread use in rapidly reporting emergencies and in numerous acts of often health-relevant 'cellular Samaritanism'.


Complications of nonvascular interventions and their management: case-based review.
The educational objectives of this continuing medical education activity are for the reader to exercise, self-assess, and improve his or her skills in diagnostic radiology with regard to the complications of nonvascular interventions and their management. The six scenarios in this article review how and why complications occur in nonvascular interventional procedures and how to manage them.


Cloning and characterisation of the RBCC728/TRIM36 zinc-binding protein from the tumor suppressor gene region at chromosome 5q22.3.
DNA alterations at chromosome 5q22 occur frequently in different types of tumors including urological cancers. Previously, we narrowed a common target region between loci D5S659 and D5S2055 at chromosome 5q22.3 by microsatellite allelotyping. After constructing a BAC contig and shot-gun sequencing we identified a putative exon by the NIX software package. By PCR cloning using the putative exon (5qex5) specific primers and primers directed to the vector (lambdaZAPII) sequence of human brain and kidney cDNA libraries, we obtained a full-length cDNA of 4074 bp of the new gene RBCC728/TRIM36 (GenBank accession no.) with an ORF coding for a protein of 728 amino acids. The TRIM36, which is a new member of the tripartite motif (TRIM) gene family, shows a RING finger C3HC4 structure, two B-box, a coiled-coil, a fibronectin type III and a C-terminal domain of unknown function (SPRY). The TRIM36 has a weak homology to MID1. Immunohistochemistry of recombinant and native TRIM36 displays a cytoplasmic, slightly filamentous staining pattern in COS-7 cells. The TRIM36 is expressed in adult testis, brain, prostate, kidney, heart and lung. A variable level of TRIM36 expression was detected by Q-RT-PCR in conventional RCC, while the gene was consequently upregulated in PCs. We did not find mutation in the open reading frame of the TRIM36 in cancer cells. The overexpression of the TRIM36 in the vast majority of prostate cancer suggest that this gene might be involved in the prostate tumorigenesis.


Herbimycin-A attenuates ischaemia-reperfusion induced pulmonary neutrophil infiltration.
To determine whether pharmacological induction of heat shock proteins (HSPs) by herbimycin-A (a tyrosine-kinase inhibitor) would protect against neutrophil-mediated lung injury in an animal model of lower torso ischaemia-reperfusion. Sprague-Dawley rats were randomised into three groups: the control group underwent midline laparotomy only; the ischaemia-reperfusion (IR) group underwent laparotomy and clamping of the infrarenal abdominal aorta for 30 min followed by 2 h of reperfusion; the third group (HerbIR) was pretreated with herbimycin-A 18 h prior to IR insult. Wet to dry lung weight ratio (W:D), bronchoalveolar lavage protein concentration (BALprot), tissue myeloperoxidase activity (MPO) and bronchoalveolar lavage neutrophil count (BALPMN) were measured. Heat shock protein 72 (HSP72) expression in lung, intestine, mesentery and liver was measured using Western immunoblotting. IR resulted in acute lung injury with tissue oedema (W:D) and neutrophil infiltration (PMO, BALPMN). Herbimycin-A, in vivo, induced HSP expression and attenuated neutrophil infiltration (MPO, BALPMN). These data indicate that herbimycin-A protects against ischaemia-reperfusion induced pulmonary neutrophil infiltration, possibly by increasing the expression of heat shock proteins.


Origin of the thoracic duct and pancreaticoduodenal lymphatic pathways to the para-aortic lymph nodes.
We investigated the afferent and efferent connections of the para-aortic lymph nodes (group 16 nodes) relative to the origin of the thoracic duct in 85 postmortem cadavers. The origin was usually restricted to groups 16b1-inter and -latero nodes (type I; 90.6%), regardless of whether the union of their efferents occurred at the abdominal or thoracic level. We also occasionally observed thick collecting vessels originating from the dorsal aspect of the pancreaticoduodenal region, running along the right side of and superficial to the celiac plexus and emptying into group 16b1 nodes. The thoracic duct originated occasionally not only from group 16b1 nodes but also from group 16a2 nodes (type II; 9.4%). Moreover, in all 85 specimens, the group 16a2-inter node often received afferents from the celiac plexus itself or the tight connective tissue between the plexus and diaphragmatic crus, or both. The results support the reliability of the extended D2 lymphadenectomy (D2 + group 16b1 nodes + group 16a2-inter node) for curative cancer surgery in the pancreaticoduodenal region.


Mouse T-cell-dependent proliferative response to syngeneic serum modified with various agents used in root canal therapy.
Syngeneic sera modified with seven agents were used as the immunogens to induce lymph-node cell proliferation in C57BL/6 mice. Immunogenicity could be conferred upon tolerated syngeneic serum by modification with diluted tincture of iodine (J) or formocresol (FC). However, the synergistic action of formalin and cresol appeared to be an indispensable condition in acquiring immunogenicity of FC-modified syngeneic serum (FC-MS). Moreover, immunological tolerance to native serum was not terminated after injection of J-MS or FC-MS. These proliferative functions were dependent on Lyt-1 cells. The cells directed against J- or FC-modified syngeneic serum were specific for the immunizing hapten J or FC. However, they did not recognize the hapten per se, but rather, the conjugate-specific determinants, i.e. these contributed by both the hapten and the self-carrier.


An autopsy case of pyruvate kinase deficiency anemia associated with severe hemochromatosis.
We report an autopsy case of pyruvate kinase deficiency anemia with severe hemochromatosis. This anemia is rarely associated with hemochromatosis. In this case, the autopsy findings showed hemochromatosis of the heart, pancreas, liver, kidneys, thyroid gland, adrenal glands, testes and skin. Microscopic examination showed iron depositions in these organs, but not in the bone marrow. A family study showed negative data for iron overload and no known HLA type suggestive of idiopathic hemochromatosis. To explain this rare association, we suggest that this patient's iron overload was an acquired type, which might have mainly been caused by increased iron absorption due to the severe hemolytic anemia.


[Bach transcription factors regulate hematopoietic stem/progenitor cell differentiation in response to environmental changes].
Differentiation of hematopoietic stem/progenitor cells should be tightly regulated depending on the environmental changes to maintain homeostasis. For example, erythropoiesis repression and myelopoiesis induction are widely recognized as infectious/inflammatory conditions. Transcription factors are expected to play significant roles in achieving such alterations. However, the precise mechanism by which the differentiation trajectory shift is controlled under environmental changes has not fully been elucidated. In this study, we showed that Bach transcription factors organize the erythro-myeloid differentiation in hematopoietic stem/progenitor cells in response to the environmental changes. Under the steady state, Bach transcription factors support erythroid differentiation and repress myeloid differentiation by regulating the expression of their target genes. In contrast, the functions of Bach transcription factors were repressed, which induced myelopoiesis and repressed erythropoiesis, under emergency conditions, such as infection/inflammation. Competitive roles of Bach transcription factors and C/EBP, the key regulator of myelopoiesis, might be important for tuning erythro-myeloid differentiation trajectory and its shift in response to infection/inflammation. Disfunction of Bach transcription factors was considered to be related to anemia in chronic inflammation and myelodysplastic syndromes. In addition, considering previous findings, Bach2 might possess important roles in the conditioning of the hematopoietic system for subsequent emergency conditions.


Reversal of optic disc cupping after glaucoma surgery analyzed with a scanning laser tomograph.
To detect and quantitate changes in optic nerve morphology after glaucoma surgery using the Heidelberg Retina Tomograph (HRT, Heidelberg Instruments, Heidelberg, Germany). Nonconsecutive observational case series. The authors prospectively enrolled 21 adult patients undergoing incisional glaucoma surgery for progressive glaucoma damage. Quantitative analysis of the optic nerve head by scanning laser tomography and automated perimetry were performed before and after glaucoma surgery. Changes in optic nerve parameters were subjected to linear regression analysis with respect to percent of postoperative reduction of intraocular pressure (IOP), as well as with respect to age, refraction, preoperative cup:disc ratio, and change in visual field parameters. Seventeen patients had pre- and postoperative images suitable for analysis. Mean IOP at the time of image acquisition before surgery was 30.5+/-12 mm Hg, and after surgery 11.8+/-5.2 mm Hg (mean follow-up, 26+/-7 weeks). Eleven of 13 (85%) patients having IOP reduction of greater than 40% showed improvement in optic disc parameters. All four patients with less than 25% reduction in IOP showed worsening of most parameters. Changes in optic disc parameters were highly correlated with percent IOP reduction and with age. The parameters in which change most strongly correlated with percent change of IOP were cup area, rim area, cup:disc ratio, and mean cup depth (each, P<0.005). The age of the patient correlated highly with change in maximum cup depth (P<0.005). Refraction and clinically determined cup:disc ratio correlated poorly with changes in measured optic disc parameters. Clinical improvement in visual fields was correlated with the degree of improvement of cup:disc ratio (P = 0.025). Most patients showing a 40% lowering of IOP after glaucoma surgery show improved optic nerve morphology as measured by the HRT. The amount of improvement correlated highly with the percent reduction of IOP.


Effectiveness and Safety of rhIGF-1 Therapy in Children: The European Increlex® Growth Forum Database Experience.
We report data from the EU Increlex® Growth Forum Database (IGFD) Registry, an ongoing, open-label, observational study monitoring clinical practice use of recombinant human insulin-like growth factor-1 (rhIGF-1) therapy in children. Safety and effectiveness data on rhIGF-1 treatment of 195 enrolled children with growth failure were collected from December 2008 to September 2013. Mean ± SD (95% CI) height velocity during first year of rhIGF-1 treatment was 6.9 ± 2.2 cm/year (6.5; 7.2) (n = 144); in prepubertal patients naïve to treatment, this was 7.3 ± 2.0 cm/year (6.8; 7.7) (n = 81). Female sex, younger age at start of rhIGF-1 therapy, and lower baseline height SDS predicted first-year change in height SDS. The most frequent targeted treatment-emergent adverse events (% patients) were hypoglycemia (17.6%, predictors: young age, diagnosis of Laron syndrome, but not rhIGF-1 dose), lipohypertrophy (10.6%), tonsillar hypertrophy (7.4%), injection site reactions (6.4%), and headache (5.9%). Sixty-one serious adverse events (37 related to rhIGF-1 therapy) were reported in 31 patients (16.5%). Safety and effectiveness data on use of rhIGF-1 in a 'real-world' setting were similar to those from controlled randomized trials. Severe growth phenotype and early start of rhIGF-1 improved height response and predicted risk of hypoglycemia.


E-cadherin nuclear staining is useful for the diagnosis of ovarian adult granulosa cell tumor.
We recently have demonstrated nuclear localization of E-cadherin in ovarian adult granulosa cell tumors (Histopathology 2011;58:423). The purpose of the present study is to investigate the diagnostic utility of E-cadherin nuclear staining for the differential diagnosis between ovarian adult granulosa cell tumor and its morphological mimics. Tissue samples taken from 81 ovarian tumors and 20 extraovarian tumors were immunohistochemically stained using monoclonal anti-E-cadherin antibody recognizing cytoplasmic domain (clone 36 supplied by BD Biosciences, San Jose, CA). The ovarian tumors consisted of 30 adult granulosa cell tumors, 3 Sertoli-stromal cell tumors, 14 fibrothecomas, 5 carcinoid tumors, 1 large cell neuroendocrine carcinoma, 18 endometrioid adenocarcinomas, and 10 poorly differentiated serous adenocarcinomas. Extraovarian tumors consisted of 16 uterine endometrial stromal neoplasms and 4 pulmonary small cell carcinomas. Only tumor cells with nuclear staining were considered positive in this study. Ninety percent of adult granulosa cell tumors, 67% of Sertoli-stromal cell tumors, 64% of fibrothecomas, 75% of endometrial stromal neoplasms, 75% of small cell carcinomas, and the one large cell neuroendocrine carcinoma showed E-cadherin nuclear expression, whereas all the ovarian carcinoid tumors, endometrioid adenocarcinomas, and poorly differentiated serous adenocarcinomas were negative. E-cadherin nuclear staining is useful in distinguishing between adult granulosa cell tumors and ovarian adenocarcinomas or carcinoid tumors. However, it is of limited use for distinguishing between adult granulosa cell tumors and endometrial stromal neoplasms or small cell carcinomas. E-cadherin should be included in the immunohistochemical panel for an accurate diagnosis of ovarian adult granulosa cell tumors.


Juvenile Nasopharyngeal Angiofibroma With Sphenoid Sinus Invasion and Protrusion: Treatment Approach With Le Fort I Osteotomy.
Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign tumor that occurs predominantly in young males. The authors report the case of a 22-year-old male patient who presented with a painless, exophytic tumor mass protruding through the right nostril, with anterior lateral extension associated with severe posterior involvement, erosion of the sphenoid bone to the right of the pterygoid process, and significant epistaxis. The preoperative evaluation, surgical approach, postoperative results, and a review of the literature are presented. The surgical approach with Le Fort I osteotomy was designed to facilitate surgical access to the tumor in the nasal cavity. Before down-fracture of the maxilla, plates were placed for fixation and holes were made to produce reference points for restoration of normal anatomy after tumor removal. Although the literature describes the use of nonsurgical therapies, it is well established that surgical treatment is the best option for patients with JNA. Treatment also requires preoperative embolization to avoid bleeding and ensure safety during tumor resection. Long-term imaging follow-up every 6 to 8 months for at least 3 years after surgery is needed for detection of residual tumor/recurrence. The modified technique used here together with preoperative embolization was essential to successful outcome.


EMG activity does not change during a time trial in competitive cyclists.
The purpose of the present study was to measure the electromyographic (EMG) activity of four lower limb muscles and the propulsive torque during a cycling time-trial (TT). Nine competitive cyclists (V.O (2max): 73.8 +/- 5.3 ml . min (-1) . kg (-1)) performed two tests separated over a one-week period on a friction-load cycle ergometer equipped with a SRM crankset scientific system: 1) a continuous incremental test for the determination of the peak power output (PPO); and 2) a 30-min TT test at a self-selected work intensity. The EMG activity of the vastus medialis (VM), the rectus femoris (RF), the biceps femoris (BF), and the gastrocnemius medialis (GAS), and the propulsive torque were recorded every 5 min for 10 s. There was no time effect on the power output, the pedalling cadence, and the mean propulsive torque. The EMG activity of the VM and the RF muscles was unchanged during the TT (p > 0.05). The EMG activity of the two knee flexor muscles (BF and GAS) tended to increase with time but it was not significant (p > 0.05). The EMG/torque of the VM and the RF muscles tended to decrease with time but it was not significant (p > 0.05). The lack of increase in the EMG activity of the four investigated muscles seems to indicate that the subjects performed the TT test at a muscular work steady-state.


R-Smad signaling-mediated VEGF expression coordinately regulates endothelial cell differentiation of rat mesenchymal stem cells.
A low-efficiency yield hinders the use of stem cells as a source of endothelial cells (ECs) for therapeutic vascularization, and the diversity of the transforming growth factor-β (TGF-β) superfamily has undermined understanding the effects of its potent vascularization-inducing. Herein, we studied the role of the TGF-β superfamily in EC differentiation of rat bone marrow mesenchymal stem cells (MSCs) induced by Smad2/3 and Smad1/5/8 signaling. MSCs that had been sorted by flow cytometry as CD31-negative were cultured for 14 days in medium supplemented with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) as the control. The Smad2/3 pathway was activated by TGF-β1 and Smad1/5/8 by bone morphogenetic proteins (BMPs). In the early phase in the Smad2/3-activated group, there were 10% CD31-positive cells, which was significantly higher than in the control group. A low Smad1/5/8 phosphorylation level after BMP4 activation doubled the number of CD31-positive cells, while a higher phosphorylation level after BMP9 activation showed no effect. A Smad2/3 inhibitor initially blocked differentiation but later promoted it, while a Smad1/5/8 inhibitor reversed the induction observed with BMPs. Moreover, the positive effects of R-Smad on differentiation were weakened by the VEGF neutralizing antibody, and a Smad3 inhibitor decreased VEGF expression and blocked differentiation in both the early and late phases. In conclusion, differentiation of ECs from MSCs via Smad2/3 signaling is stage dependent. Activation, particularly by Smad3, significantly promotes differentiation at an early phase but later is suppressive. A low Smad1/5/8 phosphorylation level has a positive effect, and R-Smad effects are partly mediated by VEGF.


Kinematic analyses of air-stepping in normal and decerebrate preweanling rats.
We studied the ability of L-DOPA (100 mg/kg, subcutaneous) to elicit air-stepping in decerebrate and sham-operated Sprague-Dawley rats from postnatal Day 5 through postnatal Day 20. The most common gait consisted of fore- and hindlimb alternation, but between 10 and 20 days of age, patterns of coordination resembling swimming, in which the forelimbs remained adducted, and galloping became more frequent in both decerebrate and sham-operated rats. Because episodes of galloping were rarely more than two or three step cycles in length, our analyses focused on episodes of stepping in which limbs within the girdles stepped in alternation and diagonal pairs of limbs moved in synchrony ("trot"). The rate of stepping of both decerebrate and sham-operated rats increased from about 2.9 steps/s at Day 5 to about 4 steps/s at Day 20. In both groups, this increase was found to result from a decrease in the duration of the retraction phase of the step cycle. Amplitudes of movement at the wrist, knee, and ankle increased with age in both decerebrate and sham-operated neonates, whereas those of the shoulder, elbow, and hip did not change in either group. The timing of movements at joints within each limb also changed similarly with age in sham-operated and decerebrate pups. During development, forelimb movement was increasingly led by the wrist, which was followed by the elbow and then finally by the shoulder. Hindlimb movements were increasingly led by the knee, followed by the ankle, and finally by the hip. At all ages, diagonal limbs moved in synchrony, and heterolateral limbs within each girdle moved in antiphase. However, the phase relationship between hindlimb and forelimb movements changed both in sham-operated rats and in decerebrate rats during ontogeny. On Day 5, movement of each hindlimb was phase-delayed relative to that of the diagonal forelimb whereas on Days 15 and 20, the hindlimb was phase-advanced. The parallel emergence of different gaits and the similarity of coordination during diagonal progression in sham-operated and decerebrate pups show that age-related changes in gait are mediated no more rostrally than the midbrain.


Microbial Bioleaching of Ag, Au and Cu from Printed Circuit Boards of Mobile Phones.
Electronic waste (E-Waste) is consumed at high speed in the world. These residues contain metals that increase their price each year, generating new research on the ability of microorganisms to recover the metals from these wastes. Therefore, this work evaluated the biologic lixiviation of Cu, Ag and Au from printed circuit boards (PCB) of mobile phones by three strains of Aspergillus niger, Candida orthopsilosis, Sphingomonas sp. and their respective consortia, in addition to leaching with citric acid. The microorganisms were cultured in mineral media with 0.5 g of PCB, and the treatments with 1M citric acid were added the same amount of PCB. All treatments were incubated for 35 days at room temperature. The results showed that Sphingomonas sp. MXB8 and the consortium of C. orthopsilosis MXL20 and A. niger MXPE6 can increase their dry biomass by 147% and 126%, respectively, in the presence of PCB. In the bioleaching of metals, the inoculation of A. niger MXPE6, the consortium of Sphingomonas sp. MXB8/C. orthopsilosis MXL20 and Sphingomonas sp. MXB8 leached 54%, 44.2% and 35.8% of Ag. The consortium of A. niger MX5 and A. niger MXPE6 showed a leaching of 0.53% of Au. A. niger MX5 leaching 2.8% Cu. Citric acid increased Cu leaching by 280% compared to treatments inoculated with microorganisms. Although further research is required, A. niger MXPE6 and the consortium of Sphingomonas sp. MXB8/C. orthopsilosis MXL20 could be an alternative to recover Ag from PCB of mobile phones.


A disease-specific quality of life instrument for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: CLDQ-NAFLD.
Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are the most common causes of chronic liver disease with known negative impact on patients' health-related quality of life. Our aim was to validate a disease-specific health-related quality of life instrument useful for efficacy trials involving patients with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. From a long item selection questionnaire, we selected relevant items which, by factor analysis, were grouped into domains constituting Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version. The developed instrument was subjected to internal validity, test-retest reliability and construct validity assessment using standard methods. For development of the Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version instrument, a 75-item-long item selection questionnaire was administered to 25 patients with non-alcoholic fatty liver disease. After item reduction, factor analysis found that 98.7% of variance in the remaining items would be explained by six factors. Thus, the resulting Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version instrument had 36 items grouped into six domains: Abdominal Symptoms, Activity, Emotional, Fatigue, Systemic Symptoms, and Worry. The independent validation group included another 104 patients with non-alcoholic fatty liver disease. The Cronbach's alphas of 0.74-0.90 suggested good to excellent internal consistency of the domains. Furthermore, the presence of obesity and history of depression were discriminated best by Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version scores (P<.05). The domains' correlations with the most relevant domains of Short Form-36 exceeded 0.70. Test-retest reliability in a subgroup of patients (N=27) demonstrated no significant within-patient variability with multiple administrations (all median differences were zero, all P>.15, intraclass correlations .76-.88). The Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version is a disease-specific health-related quality of life instrument developed and validated using an established methodology and useful for clinical trials of non-alcoholic fatty liver disease.


Formation of a large-scale ordered honeycomb pattern by an organogelator via a self-assembly process.
We have developed a facile strategy to fabricate a large-scale, orderly-patterned honeycomb structure by using supramolecular self-assembly of a low mass organic molecule.


Decreased susceptibility to lipid peroxidation of Goto-Kakizaki rats: relationship to mitochondrial antioxidant capacity.
The respiratory function and the antioxidant capacity of liver mitochondrial preparations isolated from Goto-Kakizaki non-insulin dependent diabetic rats and from Wistar control rats, with the age of 6 months, were compared. It was found that Goto-Kakizaki mitochondrial preparations presented a higher coupling between oxidative and phosphorylative systems, compared to non-diabetic preparations. Goto-Kakizaki mitochondria presented a lower susceptibility to lipid peroxidation induced by ADP/Fe2+, as evaluated by the formation of thiobarbituric acid substances. The decreased susceptibility to peroxidation in diabetic rats was correlated with an increase in mitochondrial vitamin E (alpha-tocopherol) content and GSH/GSSG ratio. Moreover, the glutathione reductase activity was significantly increased, whereas the glutathione peroxidase was decreased. Superoxide dismutase activity was unchanged in diabetic rats. Fatty acid analyses showed that the content in polyunsaturated fatty acids of Goto-Kakizaki mitochondrial membranes was significantly higher compared to controls. These results indicate that the lower susceptibility to lipid peroxidation of mitochondria from diabetic rats was related to their antioxidant defense systems, and may correspond to an adaptative response of the cells against oxidative stress in the early phase of diabetes.


[Contraception and family planning services as viewed by users of three clinics in the Unified National Health System, Rio de Janeiro State, Brazil].
This article presents partial data from a larger qualitative, socio-anthropological survey in five States of Brazil, aimed at grasping the perspectives of users in urban and rural areas on their contraceptive and reproductive experiences, and their perceptions concerning contraceptive and family planning care in the Unified National Health System. The article focuses on findings in the State of Rio de Janeiro from 60 individual semi-structured interviews with users 18 to 49 years of age in two primary care clinics in the State capital and one rural clinic under the Family Health Program (FHP). There was a greater diversity in the use of methods in the capital as compared to the interior, where tubal ligation was the only alternative to the pill. Group education work in the capital expands the possibilities for choice of methods and collective learning, although access to the IUD and tubal ligation is still considered problematic, due to difficulties in providing such care. The health services prioritize care for women that have already begun childbearing, and more care is needed for non-pregnant adult women and adolescents, in addition to strengthening the educational work in the FHP.


Peripheral bombesin induces gastric vagal afferent activation in rats.
Bombesin's influence on gastric vagal afferent discharge (GVAD) was studied in urethan-anesthetized rats. Vehicle and peptides were injected intravenously at 30-min intervals. Cholecystokinin (CCK; 300 pmol) and bombesin (300 pmol) increased ongoing multiunit GVAD by 153 +/- 59 and 162 +/- 37%, respectively; similar increases were induced by a second injection of bombesin and CCK. The bombesin antagonist, ICI-216140, prevented bombesin-induced increase in GVAD, whereas the CCK response was not influenced. The CCK-A receptor antagonist devazepide reduced the activation of GVAD induced by bombesin from 107 +/- 11 to 63 +/- 6%, while abolishing the CCK response. Devazepide given alone or in combination with ICI-216140 did not modify gastric distension (3 ml)-induced increase in GVAD. Of 22 single units that were activated by gastric load (4 ml), 17 and 20 units responded also to bombesin (620 pmol) and CCK (870 pmol), respectively. Of the nine units that did not respond to gastric load, eight had an increase in GVAD induced by both bombesin and CCK. There was no specific binding of 125I-labeled [Tyr4]bombesin on cervical vagus, either intact or 24 h after ligation. These data suggest that intravenous bombesin-induced stimulation of GVAD is indirect and initially mediated through specific receptor activation influencing gastric smooth muscle and the release of CCK.


[Neurological disease in measures against intractable diseases in Japan].
Japan has been taking measures to cope with intractable diseases centering on five principles: "promoting investigation and research", "providing medical care facilities", "reducing co-payment for medical costs", "improving and coordinating community-based health care", "medical care and welfare services", and "promoting welfare measures aimed at improving the quality of life (QOL)". As the object of measures, 118 diseases including serious neurological diseases (e.g. ALS, CJD, PD etc.) have been specified. Thirty years have passed since the specific diseases treatment research program was launched, during which the environment surrounding intractable diseases has changed significantly. In light of this, "Committee on Measures Against Intractable Diseases" was organized in Sept 2001 under the Health Science Council. Based on the interim report of the committee, the government is going to take new measures against the intractable diseases.


Observational evidence that diversity may increase productivity in Mediterranean shrublands.
This paper reports field observational evidence on the diversity-biomass production relationship from eastern Mediterranean shrublands dominated by Cistus salviifolius. The main results are: (1) plant diversity and ecosystem primary production are positively correlated in the Cistus shrublands, which are multigrowth form systems; (2) the taxonomic and growth form diversity in Cistus shrublands suggests that there is strong differentiation along the structural niche axis, and thus functional redundancy is weak; (3) the performance of the dominant Cistus in terms of biomass production did not affect the overall diversity-biomass production of the studied communities.


Minor thiols cysteine and cysteinylglycine regulate the competition between glutathione and protein SH groups in human platelets subjected to oxidative stress.
Changes in the concentrations of protein-mixed disulfides (XS-SP) of glutathione (GSH), cysteine (CSH), and cysteinylglycine (CGSH) were studied in human platelets treated with diamide and t-BOOH in timecourse experiments (time range, 1-30 min) in order to understand the contribution of minor thiols CSH and CGSH to the regulation of glutathione-protein mixed disulfides (GS-SP). Diamide was much more potent than t-BOOH in altering the platelet thiol composition of XS-SP (threshold dose: diamide, 0.03 mM; t-BOOH, 0.5 mM) and caused reversible XS-SP peaks whose magnitude was related to the concentration of free thiols in untreated cells. Thus maximum levels of GS-SP (8 min after 0.4 mM diamide) were about 16-fold higher than those of controls (untreated platelets, GS-SP = 0.374 nmol/10(9) platelets), whereas those of CS-SP and CGS-SP were only 4-fold increased (untreated platelets, CS-SP = 0.112 nmol/10(9) platelets; CGS-SP = 0.024 nmol/10(9) platelets). The greater effects of diamide with respect to t-BOOH were explained on the basis of the activities of fast reactive protein SH groups for diamide and glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G-6-PDH) for t-BOOH. The addition of cysteine (0.3 mM, at 4 min) after treatment of platelets with 0.4 mM diamide increased the rate of reversal of GS-SP peaks to normal values, but also caused a relevant change in CGS-SP with respect to that of platelets treated with diamide alone. An increased gamma-glutamyltranspeptidase activity was found in platelets treated with diamide. Moreover, untreated platelets were found to release and hydrolyze GSH to CGSH and CSH. Ratios of thiols/disulfides (XSH/XSSX) and activities of GR and G-6PDH were also related to a high reducing potential exerted by GSH but not by minor thiols. The lower mass and charge of minor thiols is a likely requisite of the regulation of GS-SP levels in platelets.


Pomace limits tannin retention in Frontenac wines.
The impact of different factors (must protein treatment: bentonite and heat; pomace: fermented with and without; tannin addition: 0-9 g/L; and time of maceration: 0-11 days) on tannin, pigment, and protein extraction/retention in Frontenac wines was investigated. Wine tannin concentration and composition were determined by HPLC-fluorescence. Protein and pigment parameters were analysed by BCA assay and Boulton's method, respectively, using UV-spectrophotometry. Results: Bentonite and heat significantly reduced wine protein concentration at the end of alcoholic fermentation but heat was less efficient than bentonite (1.8-5.0 times less). Removing wine proteins did not improve tannin retention in wines (p > 0.1032) but fermenting without pomace significantly improved their retention (up to 2.4 times), especially that of polymeric flavan-3-ols (up to 27.8%). An addition of 3 g/L of enological tannins in wines, fermented with or without pomace, was necessary to increase wine tannin concentration significantly.


CMV prophylaxis in high-risk renal transplant patients (D+/R-) by acyclovir with or without hyperimmune (CMV) immunoglobulins: a prospective study.
In this prospective randomized study including 28 patients, we show that, in cytomegalovirus (CMV)-seronegative renal transplant recipients (R-) receiving a CMV-seropositive graft (D+), high doses of acyclovir (ACV, i.e. 3,200 mg/day) during the first 3 months after transplantation were as efficient as hyperimmune CMV immunoglobulins (CMV Igs) plus high doses of ACV regarding the prophylaxis of CMV primoinfection. Fifty-four percent of the patients in the ACV arm and 50% in the other arm presented at least one episode of viremia (n.s.). The incidence of CMV disease was 31% in the ACV group and 20% in the ACV + CMV Ig group (n.s.). By comparison with historical controls (no prophylaxis), we found that ACV with or without CMV Ig significantly delayed and significantly decreased the rate of CMV disease, although the severity score was not statistically different. Moreover, high doses of ACV were far less expensive than their combination with hyperimmune CMV Igs. Thus, until oral ganciclovir is available for the prophylaxis of primary CMV infection in renal transplant patients, we recommend the use of high doses of ACV for the first 3 months after transplantation in high-risk renal transplant patients, i.e. D+/R-.


Ensocopic-endoluminal therapies. A critical appraisal.
Due to its large prevalence, gastro-oesophageal reflux disease is an ideal target for companies developing medical devices designed to cure reflux. Indeed, because medications leave part of the patients unsatisfied, there is a potential place for alternative therapies, capable of restoring an efficacious anti-reflux barrier, but without the drawbacks of surgery. For more than a decade, several novel endoluminal therapies were developed, clinically evaluated, put on the market and, for many of them, withdrawn due to economic considerations, lack of efficacy or complications. These therapies were designed to act on the gastro-oesophageal junction and reinforce mechanically the anti-reflux barrier by three different ways: suturing, radiofrequency energy application, or implantation of foreign materials. Most of the published data come from open uncontrolled studies with short-term enthusiastic results. There are a few randomized control trials assessing the true efficacy of these modalities, showing often less impressive results than the open studies did, due to a high placebo effect in mild gastro-oesophageal reflux disease. Although endoscopic treatment of gastro-oesophageal disease is still an interesting topic of investigation, one can draw some lessons from the recent experiences and foresee which place these techniques could find in the management of patients suffering from reflux.


The combined effect of surgeon and hospital volume on health outcomes: a systematic review.
To explore the interaction between surgeon volumes (SVs) and hospital volumes (HVs) on health outcomes. We searched MEDLINE, Embase, CINAHL, Web of Science as of May 2017. We included studies investigating the interaction between high or low SVs operating in high or low HVs. Review process follows the PRISMA guidelines. We assessed the methodological quality of the included studies using validated critical appraisal checklists. Sixteen studies were included. Due to the heterogeneity of studies, it was not possible to perform a quantitative analysis. Heath outcome are worse when high SV operating in low HV vs high HV, for the majority of the conditions (colorectal cancer, cystectomy, liver resection, mitral valve surgery, pancreatico-duodenectomy). Results for low SV are better when operating in high HV vs low HV for patients undergoing pancreatic-duodenectomy for mortality, 30 days complications and length of stay. Results for low SV are worse vs high SV when operating in high HV for most considered conditions. Results were in favour of higher SV vs low SV when operating in low HV for digital replantation success after injuries, 30 days mortality and complications after pancreatic-duodenectomy. The available evidence is limited. It is necessary to increase the monitoring of the association between surgeons volumes and hospitals volumes in which they operate, to ensure fairness and accuracy of care for better health outcomes.


[DMSO arrested hybridoma cells for enhanced antibody production].
Dimethyl sulfoxide (DMSO), a well-known differentiation inducer in several myeloid cells, induces G1 phase arrest in many cell lines. In this study, we investigated the possibility of using DMSO to arrest H18 hybridoma cells to the G1 phase and monitor whether the arrest improves antibody production. We showed that DMSO in concentration ranging between 0.3% and 0.6% efficiently arrested H18 hybridoma cells in G1 phase. In our experiment, > 80% of cells grown for 36h in presence of the 0.6% DMSO were arrested in G1. Furthermore, expression levels of P27 were up-regulated tow fold during the G1 phase. Higher concentration of DMSO at 0.9% leads to cytotoxicity. Herein we show a simple way, a two-stage process for antibody production, which consists of a proliferation phase leading to the desired cell density, followed by an extended production phase during which the cells remain at G1 phase. Our observation that the addition of DMSO results in increase antibody production is of significance in further use of hybridoma cells in high density large scale cell culture.


Evolutionary pattern of the H 3 haemagglutinin of equine influenza viruses: multiple evolutionary lineages and frozen replication.
The nucleotide and deduced amino acid sequences of the haemagglutinin genes coding for the HA 1 domain of H3N8 equine influenza viruses isolated over wide regions of the world were analyzed in detail to determine their evolutionary relationships. We have constructed a phylogenetic model tree by the neighbour-joining method using nucleotide sequences of 15 haemagglutinin genes, including those of five viruses determined in the present study. This gene tree revealed the existence of two major evolutionary pathways during a twenty five-year period between 1963 to 1988, and each pathway appeared to consist of two distinct lineages of haemagglutinin genes. Furthermore, our analysis of nucleotide sequences showed that two distinct lineages of equine H3N8 viruses were involved in an equine influenza outbreak during the period of December 1971-January 1972 in Japan. The number of nucleotide changes between strains was proportional to the length of time (in years) between their isolation except for three of the HA genes. However, there are three exceptional strains isolated in 1971, 1987, and 1988, respectively. The haemagglutinin gene in these strains showed a small number of nucleotide substitutions after they branched off around 1963, suggesting an example of frozen replication. Although the estimated rate (0.0094/site/year) of synonymous (silent) substitutions of the haemagglutinin gene of equine H3N8 viruses was nearly the same as that of human H 1 and H 3 haemagglutinin genes, the rate of nonsynonymous (amino-acid changing) substitutions of the former equine virus gene was estimated to be 0.00041/site/year--that is about 5 times lower than that estimated for the human H 3 haemagglutinin gene. The present study is the first demonstration that multiple evolutionary lineages of equine H3N8 influenza virus circulated since 1963.


Quantity and species of fish consumed shape breast-milk fatty acid concentrations around Lake Victoria, Kenya.
Long-chain PUFA (LCPUFA) found in breast milk are derived from dietary sources and critical for optimal infant development. We examined associations between fish consumption and concentrations of LCPUFA and essential n-3 and n-6 fatty acids in breast milk among mothers living around Lake Victoria. We used cross-sectional analyses of associations between recent fish consumption and breast-milk fatty acid concentrations. The study was conducted around Lake Victoria on Mfangano Island, Kenya, where multiple fish species are key dietary components and also are widely exported. Breast-feeding mothers (n 60) provided breast-milk samples, anthropometric measurements and questionnaire responses. In the previous 3 d, 97 % of women consumed a mean of 178 (sd 111) g fish (~2 servings/3 d). Mean breast-milk concentrations included DHA (0·75 % of total fatty acids), EPA (0·16 %), α-linolenic acid (ALA; 0·54 %), arachidonic acid (AA; 0·44 %) and linoleic acid (LA; 12·7 %). Breast-milk DHA concentrations exceeded the global average of 0·32 % in fifty-nine of sixty samples. We found native cichlids (Cichlidae) and dagaa (Rastrineobola argentea) contributed high levels of DHA, EPA and AA to local diets. We also found evidence for associations between fish species consumed and breast-milk LCPUFA concentrations when controlling for intake of other fish species, maternal body mass, maternal age, child age and exclusive breast-feeding. The fatty acid composition of breast milk was influenced by the fish species consumed. Ensuring access to diverse fish and particularly inexpensive, locally available species, may be important for diet quality as well as infant growth and development.


Antecedents to nonorganic failure-to-thrive.
Using a retrospective cohort design with a randomly selected control group, this study investigated the relationship between selected maternal, infant, and environmental variables, and the development of nonorganic failure-to-thrive. The groups differed significantly on sex of infant and incidence of breastfeeding.


Improved amplitude evaluation of the frequency following response (FFR).
Three methods were combined to improve the evaluation of the amplitude of the frequency following response (FFR) in unfavorable signal-to-noise conditions. The first step was the application of a time-multiplex averager to reduce noise variance between amplitude values to be compared. The second step was the evaluation of amplitude in the frequency domain by means of a digital triangle filter. The third step was the correction of raw FFR amplitudes by an algorithm that takes into account several noise values.


How do changes in speed affect the perception of duration?
Six experiments investigated how changes in stimulus speed influence subjective duration. Participants saw rotating or translating shapes in three conditions: constant speed, accelerating motion, and decelerating motion. The distance moved and average speed were the same in all three conditions. In temporal judgment tasks, the constant-speed objects seemed to last longer than the decelerating objects, which in turn seemed to last longer than the accelerating stimuli. In temporal reproduction tasks, the difference between accelerating and decelerating stimuli disappeared; furthermore, watching an accelerating shape lengthened the apparent duration of the subsequent (static) display. These results (a) suggest that temporal judgment and reproduction can dissociate for moving stimuli because the stimulus influences the apparent duration of the subsequent interval, and (b) constrain theories of time perception, including those which emphasize memory storage, those which emphasize the existence of a pacemaker-accumulator timing system, and those which emphasize the division of attention between temporal and non-temporal information processing.


Simultaneous saccharification and fermentation of hemicellulose to butanol by a non-sporulating Clostridium species.
Production of lignocellulosic butanol has drawn increasing attention. However, currently few microorganisms can produce biofuels, particularly butanol, from lignocellulosic biomass via simultaneous saccharification and fermentation. Here we report discovery of a wild-type, mesophilic Clostridium sp. strain MF28 that ferments xylan to produce butanol (up to 3.2g/L) without the addition of saccharolytic enzymes and without any chemical pretreatments. Application of selective pressure from 2-deoxy-d-glucose facilitated isolation of strain MF28, which exhibits inactivation of genes (gid and ccp genes) responsible for carbon catabolite repression, thus allowing strain MF28 to simultaneously ferment a combination of glucose (30g/L), xylose (15g/L), and arabinose (15g/L) to produce 11.9g/L of butanol. Strain MF28 possesses several unique features: (i) non-sporulating, (ii) no acetone/ethanol, (iii) complete hemicellulose-binding enzymatic domain, and (iv) absence of carbon catabolite repression. These unique characteristics demonstrate the industrial potential of strain MF28 for cost-effective biofuel generation from lignocellulosic biomass.


Four-step CPR--improving skill retention.
This study is an attempt to see if simplifying the teaching of basic life support leads to better skill acquisition and retention. Forty-eight lay volunteers received instruction in CPR; 24 were taught the standard 8-step sequence whereas 24 were taught a simplified 4-step sequence. Tests of performance were carried out on a manikin before and after training. Those in the 4-step group were significantly better than those in the 8-step group at remembering the sequence of skills immediately after training (P = 0.04), 1 week later (P < 0.001) and at 6 weeks (P < 0.001). Twenty-three out of the 24 volunteers in the 4-step group got the sequence completely correct each time they were tested, in contrast to only 2 out of the 24 in the 8-step group. There was no difference, however, in the quality of performance of the skills between the two groups. In addition, it was shown that use of the 4-step sequence should result in a useful reduction in the time taken before a rescuer calls for the emergency services and commences CPR. Whether such a radical change in teaching should be introduced is a matter for further discussion and research.


Nutrition and growth analysis of very low birth weight infants.
The growth and nutrition of 220 very low birth weight infants were reviewed after comprehensive data on all infants in the hospital were entered into the Neonatal Intensive Care Unit Audit Data Base for 2 years prospectively. Fluid and energy (parenteral and oral) intakes were compared in four birth weight categories (1, less than or equal to 750 g; 2, 751 to 1000 g; 3, 1001 to 1250 g; 4, 1251 to 1500 g). Parenteral nutrition was the major source of first nutrition for the small infants, but seldom did it alone provide adequate nutrition for very low birth weight infants. The age of the first nutrition (parenteral and/or oral nutrition other than dextrose) decreased with increasing birth weight. The age of the first oral feedings was later for the infants of the lower birth weights but enteral feeding became the major nutrition for all weight categories by the second week of life. During the first 50 days the infants accumulated a deficit of 3780 to 5460 kJ relative to their estimated need of 504 kJ/kg per day, with the smaller infants accumulating a significantly larger deficit. The growth of infants appropriate for gestational age and of infants small for gestational age differed from each other and from the commonly used graph of Dancis et al (J Pediatr. 1948;33:570-572).


Staphylococcus aureus skin colonization in atopic dermatitis children is associated with decreased IFN-gamma production by peripheral blood CD4+ and CD8+ T cells.
Atopic dermatitis (AD) is a chronic inflammatory skin disorder, which is associated with an increased expression of Th2 cytokines with concomitant decrease in IFN-gamma production by circulating CD4+ and CD8+ T cells. The skin of patients with AD is often colonized by Staphylococcus aureus, which may reflect in changes in immunological parameters. The aim of the study was flow cytometric measurement of some peripheral blood lymphocyte subsets expressing naive/memory marker (RA/RO) and activation marker (CD25) as well as intracellular production of IFN-gamma by peripheral blood CD4+ and CD8+ T cells from varied severity AD children and determine the impact of S. aureus skin colonization on cytokines profiles. There was a significant increase in the percentage of CD4+ and CD8+ T cells producing IL-4 and IL-13 and decrease in the percentage of CD4+ and CD8+ T cells producing IFN-gamma upon in vitro stimulation with phorbol 12-myristate 13-acetate and ionomycin in children with AD compared to healthy ones. The absolute number of CD4+ and CD8+ T cells expressing memory marker CD45RO was elevated as compared with controls. The severity of AD was positively correlated with the percentage of lymphocyte subsets: CD45RO+, CD4+CD45RO+, and the percentage of CD3+ and CD4+ expressing CD25 as well as the number of S. aureus on the skin. In conclusion, both CD4+ and CD8+ memory T cells are involved in the immunopathogenesis of AD. S. aureus skin colonization is related with disease severity and changes in expression of CD45RO and CD25 on T cells. A decrease in the percentage of CD4+ and CD8+ T cells producing IFN-gamma in AD children may explain propensity for skin infection.


Perioperative therapies - Enhancing the impact of cancer surgery with repurposed drugs.
Surgical resection remains the major modality for modern curative treatment for solid tumours. However, post-surgical recurrence, even following clear-margin resection and adjuvant treatment, remains common in many types of cancer. Reducing recurrence rates, therefore, offers the potential to increase cure rates and increase overall survival. Perioperative therapies, simple interventions during the perioperative period, are designed to address some of the factors which influence post-surgical recurrence. A range of perioperative therapies are introduced and the rationale for further clinical investigation outlined.


Clinical utility of certain biomarkers as predictors of breast cancer with or without metastasis among Egyptian females.
The objective of this study is to explore and correlate the value of certain biomarkers in breast cancer (BC) females with and without metastasis after undergoing the surgical treatment protocol in the National Cancer Institute in Egypt. Thirty females (33-69 years), diagnosed as early breast cancer patients with or without metastasis, and 20 healthy individuals were selected for this study. The biomarkers under investigation were vascular endothelial growth factor (VEGF), C-reactive protein (CRP), interleukin-6 (IL-6), and interleukin-8 (IL-8). The correlation between these markers and the tumor grade was also evaluated. The results revealed a significant increase (p < 0.0001) in VEGF, CRP, IL-6, and IL-8 in breast cancer patients with or without metastasis as compared to the healthy group. Surgical treatment of metastatic BC females showed a significant reduction of those parameters by variable degrees, whereas BC females without metastasis recorded the most inhibition levels. Also, there was positive correlation (p < 0.0001) between those biomarkers and the tumor grades. We also noticed an association between VEGF and IL-8 as well as CRP and IL-6. In conclusion, the selected biomarkers may be beneficial for the prognosis of breast cancer and seem to be a diagnostic tool to differentiate between BC with or without metastasis. The descried surgical treatment protocol succeeded to attenuate the elevated biomarker levels and improve patient survival which deserves more extensive studies.


Inhibition of coagulation and platelet adhesion to extracellular matrix by unfractionated heparin and a low molecular weight heparin.
In 7 healthy volunteers, the effect of a single i.v. injection of 52 mg (7,500 IU) of an unfractionated heparin (UFH) and of 52.5 mg (5,000 anti XaU) of a low molecular weight heparin (LMWH) on coagulation parameters and platelet function has been studied. Thrombin-induced platelet aggregation was inhibited after the injection of both heparins. There was no significant change of ADP or collagen-induced aggregation after LMWH of UFH. Platelet adhesion to bovine extracellular matrix was not inhibited by UFH but was significantly reduced after addition in vitro and ex vivo after administration of LMWH. Further investigation should establish the time course of LMWH effects on platelet adhesion. A long duration of this effect could be partially correlated with the antithrombotic effects of LMWH.


Sentence production by aphasic patients in a constrained task.
Sixty aphasic patients and 55 normal control subjects were tested on a sentence production protocol that required subjects to produce specific sentence types from semantic representations. Normal subjects produced the expected targets with great reliability. Analysis of the patients' performance indicated that patients had difficulty producing both grammatical forms and thematic roles. Patients had more trouble producing grammatical elements than content words, and showed differential difficulty on sentence types that had more grammatical elements and in which the order of thematic roles was non-canonical. The results provide evidence regarding the processing load imposed by different components of the sentence production process.


Shape-Memory Hydrogels: Evolution of Structural Principles To Enable Shape Switching of Hydrophilic Polymer Networks.
The ability of hydrophilic chain segments in polymer networks to strongly interact with water allows the volumetric expansion of the material and formation of a hydrogel. When polymer chain segments undergo reversible hydration depending on environmental conditions, smart hydrogels can be realized, which are able to shrink/swell and thus alter their volume on demand. In contrast, implementing the capacity of hydrogels to switch their shape rather than volume demands more sophisticated chemical approaches and structural concepts. In this Account, the principles of hydrogel network design, incorporation of molecular switches, and hydrogel microstructures are summarized that enable a spatially directed actuation of hydrogels by a shape-memory effect (SME) without major volume alteration. The SME involves an elastic deformation (programming) of samples, which are temporarily fixed by reversible covalent or physical cross-links resulting in a temporary shape. The material can reverse to the original shape when these molecular switches are affected by application of a suitable stimulus. Hydrophobic shape-memory polymers (SMPs), which are established with complex functions including multiple or reversible shape-switching, may provide inspiration for the molecular architecture of shape-memory hydrogels (SMHs), but cannot be identically copied in the world of hydrophilic soft materials. For instance, fixation of the temporary shape requires cross-links to be formed also in an aqueous environment, which may not be realized, for example, by crystalline domains from the hydrophilic main chains as these may dissolve in presence of water. Accordingly, dual-shape hydrogels have evolved, where, for example, hydrophobic crystallizable side chains have been linked into hydrophilic polymer networks to act as temperature-sensitive temporary cross-links. By incorporating a second type of such side chains, triple-shape hydrogels can be realized. Considering the typically given light permeability of hydrogels and the fully hydrated state with easy permeation by small molecules, other types of stimuli like light, pH, or ions can be employed that may not be easily used in hydrophobic SMPs. In some cases, those molecular switches can respond to more than one stimulus, thus increasing the number of opportunities to induce actuation of these synthetic hydrogels. Beyond this, biopolymer-based hydrogels can be equipped with a shape switching function when facilitating, for example, triple helix formation in proteins or ionic interactions in polysaccharides. Eventually, microstructured SMHs such as hybrid or porous structures can combine the shape-switching function with an improved performance by helping to overcome frequent shortcomings of hydrogels such as low mechanical strength or volume change upon temporary cross-link cleavage. Specifically, shape switching without major volume alteration is possible in porous SMHs by decoupling small volume changes of pore walls on the microscale and the macroscopic sample size. Furthermore, oligomeric rather than short aliphatic side chains as molecular switches allow stabilization of the sample volumes. Based on those structural principles and switching functionalities, SMHs have already entered into applications as soft actuators and are considered, for example, for cell manipulation in biomedicine. In the context of those applications, switching kinetics, switching forces, and reversibility of switching are aspects to be further explored.


Examining Listener Reaction Time in the Perceptual Assessment of Dysarthria.
In the perceptual assessment of dysarthria, various approaches are used to examine the accuracy of listeners' speech transcriptions and their subjective impressions of speech disorder. However, less attention has been given to the effort and cognitive resources required to process speech samples. This study explores the relationship between transcription accuracy, comprehensibility, subjective impressions of speech, and objective measures of reaction time (RT) to further examine the challenges involved in processing dysarthric speech. Sixteen listeners completed 3 experimental listening tasks: a sentence transcription task, a rating scale task, and an RT task that required responses to veracity statements. In each task, the speech stimuli included speech from 8 individuals with dysarthria. Measurements from the 3 tasks were significantly related, with a correlation coefficient of -0.94 between average RT and transcription-based intelligibility scores and -0.89 between RT and listener ratings of dysarthria. Interrater reliability of RT measurements was relatively low when considering a single person's response to stimuli. However, reliability reached an acceptable level when a mean was taken from 8 listeners. RT tasks could be developed as a reliable adjunct in the assessment of listener effort and speech processing.


Rostral pontile mechanisms regulate durations of expiratory phases.
Neural expiration can be divided into two phases. Phase I corresponds to the period of laryngeal adduction, whereas many spinal nerves reach peak discharge in phase II. The present studies evaluated the hypothesis that rostral pontile mechanisms contribute to determining the time of onset of spinal motoneuronal activities in phase II. In decerebrate and paralyzed cats, efferent activities were recorded from the phrenic nerve and from single fibers of the branch of the intercostal nerve innervating the triangularis sterni muscle. These activities were recorded in eupnea and apneusis; the latter was produced by cooling the rostral pons by a fork thermode. In eupnea, there was a delay between the rapid decline of phrenic discharge from peak levels and the commencement of activities of motoneurons of the triangularis sterni. This delay was significantly reduced in apneusis. Peak discharge frequencies of triangularis sterni motoneurons were the same in eupnea and apneusis. We conclude that rostral pontile mechanisms contribute significantly to defining the phases of neural expiration.


When still waters become a soul tsunami: using the Tidal Model to recover from shipwreck.
The Tidal model, created by Phil Barker and Poppy Buchanan-Barker, metaphorically employs the natural resource of water to describe the person in crisis and offer a model toward recovery. The model, a midrange nursing theory used primarily in mental health settings, is applied to a women in crisis related to failed infertility treatment who attempts suicide.


Induction of carboxylesterase isozymes in Bombyx mori by E. coli infection.
Many proteins, including antibacterial peptides in the hemolymph, are induced by bacterial infections. We found two bacterially inducible carboxylesterases (CEs) in the hemolymph of the silkworm, Bombyx mori. CEs Est-1 and 2 were induced by lipopolysaccharide injection after 6 hours as well as E. coli infection. We found that bacterially inducible CEs clearly differed from noninducible CEs, including juvenile hormone esterases, in pI values, migration on analytical native PAGE, and inhibitor sensitivity. We are now studying the features and functions of these CEs.


Dependence of gonadotropin-releasing hormone-stimulated luteinizing hormone release upon intracellular Ca2+ pools is revealed by desensitization and thapsigargin blockade.
Sustained GnRH-stimulated LH release requires extracellular Ca2+, but GnRH transiently increases LH release in Ca(2+)-free medium. Here we have tested the dependence of the transient effect on intracellular Ca2+ pools. In superfused pituitary cells three Ca(2+)-mobilizing stimuli (GnRH, A23187, and endothelin-1) all caused sustained increases in LH release in normal medium (plateau responses), but only transient increases in Ca(2+)-free medium (spike responses). In Ca(2+)-free medium, GnRH (10(-10) or 10(-9) M) increased LH release transiently and desensitized the cells to the LH-releasing effect of subsequent stimulation with 10(-7) M GnRH. This desensitization was reversed by brief exposure to Ca(2+)-containing medium between the two GnRH stimulation periods. Heterologous desensitization between GnRH and A23187 and between GnRH and endothelin-1 also occurred in Ca(2+)-free medium. Thapsigargin, which inhibits the endoplasmic reticulum Ca(2+)-ATPase and thereby elevates cytosolic Ca2+, stimulated LH release (EC50, approximately 20 microM) in static culture, an effect which, unlike those of GnRH and A23187, was not markedly reduced in Ca(2+)-free medium. Low doses of thapsigargin, which had no effect on LH release alone, inhibited both sustained GnRH-stimulated LH release from static cultures in normal medium and transient GnRH-stimulated LH release from cells superfused in Ca(2+)-free medium. These data suggest that the spike phase of GnRH-stimulated LH release is not only associated with but is also dependent upon the mobilization of a GnRH- and thapsigargin-sensitive intracellular Ca2+ pool and that the Ca2+ pool mediating this GnRH effect is identical to or substantially interchangeable with A23187- and endothelin-1-mobilizable intracellular Ca2+ pools. Inhibition of sustained GnRH-stimulated LH release by thapsigargin also suggests the involvement of an intracellular Ca2+ pool in this phase of GnRH action.


[Distribution characteristics and edge effect of soil water and salt in silvopastoral system of the Yellow River Delta, China].
We measured soil water and salt distribution characteristics at 0-40 cm soil depth in a silvopastoral system of Fraxinus chinensis and Robinia pseudoacacia mixed forest × Medicago sativa, which is located in Land Use Scientific Observation Field Base of Ministry of Land and Resource in Wudi, Shandong Province, China. The moving split-window technique was used to analyze the internal-system edge effect. The results showed that both soil water and salt contents in this system heterogeneously distributed in the horizontal direction. The variation of soil water was greater and that of soil salt contents was the smaller when closer to the soil surface. With the mixed forest tree row as the boundary line, the contents of soil water and salt on both sides showed similar change trend. With the decreases of distance to the tree row, soil water content reduced first and then increased but the salt contents had a stable fluctuation at 0-10 cm soil layer. Soil water content showed a trend of decrease-flat-decrease but the salt contents first enhanced and then reduced at 10-20 cm soil layer, respectively. At the deeper soil layer (20-40 cm), the water content fluctuated stably but the salt content continued increasing. Both the contents of soil water and salt in the vertical direction increased significantly with soil depth. Except HCO3- and K+, there was a similar change trend between ions and total salt content in the soil of silvopastoral system, and the correlation between these ions and total salt content was Na+>Cl->SO42->Mg2+>Ca2+. Based on the technique of moving split-window, the edge effect zone of soil water in the silvopastoral system was 2.5 m from the east side of the tree row to 2 m from the west side. Soil salinity in the silvopastoral system was mainly affected by the tree row within the range of 1.0 m, and by both of the tree row and M. sativa within the range of 1.0-3.0 m.


Evolutionary implications of intra- and interspecific molecular variability of pathogenesis-related proteins.
We have examined phylogenetic relationships in seven pathogenesis-related (PR) protein families. Within-family comparisons involved 79 species, 166 amino acid sequences, and 1,791 sites. For 37 species, 124 different PR isoforms were identified (an average of 3.3 per species). Thirty-one of the 37 species investigated tended to cluster together (84%). Of the 17 clusters distinguished in the seven phylogenetic trees, 10 (59%) were in agreement with their taxonomic status, ascertained at the family level. The strong similarities among the intraspecific forms, as compared to interspecific differences, argue for some kind of gene conversion, but the rare occurrence of widely different isoforms also suggests diversifying selection. PRs 1, 6, and 4 seem to be less differentiated than PRs 3, 2, 10, and 5.


ACTH Gel in Resistant Focal Segmental Glomerulosclerosis After Kidney Transplantation.
Treatment of focal segmental glomerular sclerosis (FSGS) after kidney transplantation is challenging with unpredictable outcomes. The objective was to investigate the use of adrenocorticotropic hormone (ACTH) analogue gel in kidney transplant recipients with de novo or recurrent FSGS resistant to therapeutic plasma exchange (TPE) and/or rituximab. We performed a retrospective review of cases of de novo or recurrent resistant FSGS at 2 large US transplant centers between April 2012 and December 2016. Proteinuria was measured by urine protein to creatinine ratio. We identified 20 cases of posttransplant recurrent and de novo FSGS resistant to conventional therapy with TPE and rituximab. Mean ± SD age was 49 ± 15.5 years, 14 (70%) were male, 13 (65%) were whites, and 8 (38%) had previous kidney transplants. Median (interquartile range) of recurrent and de novo FSGS was 3 (0.75-7.5) months posttransplant. The majority of patients, 15 (75%), received TPE as a treatment at the time of diagnosis and 10 (50%) received rituximab, which was started before the use of ACTH gel. There was a significant improvement of urine protein to creatinine ratio from a mean ± SD of 8.6 ± 7.6 g/g before ACTH gel to 3.3 ± 2.3 g/g after the use of ACTH gel (P = 0.004). Ten (50%) patients achieved complete or partial remission. Although, the response varied among the recipients, ACTH gel might be an effective therapy for posttransplant resistant FSGS cases that fail to respond to TPE and rituximab.