Inter-rater Agreement for Abstraction of the Early Management Bundle, Severe Sepsis/Septic Shock (SEP-1) Quality Measure in a Multi-Hospital Health System.
The Early Management Bundle, Severe Sepsis/Septic Shock (SEP-1) quality measure is complex to abstract, which may lead to discrepancies between abstractors. This study was designed to evaluate inter-rater agreement between abstractors at individual hospitals in a health system and a lead abstractor on abstraction elements and measure compliance for SEP-1. Patient cases qualifying for abstraction for SEP-1 over a four-month period in 2016 were initially abstracted at a local hospital and then centrally by a lead abstractor. Abstraction results were retrospectively compared to determine inter-rater agreement. A total of 580 SEP-1 cases were abstracted locally and centrally. Each site contributed a median (interquartile range) of 63 (49, 86) cases. There was complete concordance of measure-related elements in 391 cases (67%) (inter-rater agreement: κ = 0.40, p < 0.01). The most common discrepancy (60 cases) was severe sepsis presentation time. There was a weak correlation between SEP-1 compliance adjudicated locally and centrally (r2 = 0.41, p < 0.01). The average change in monthly SEP-1 measure compliance at each site after central adjudication was a 1% increase but ranged from a 49% decrease to a 40% increase. Concordance on SEP-1 abstraction elements between local and expert adjudicators was fair, and SEP-1 performance varied considerably from initial site-reported performance. The detailed nature of SEP-1 can lead to unreliable abstraction, which may lead to inaccurate reporting of compliance with the measure and affect comparability of performance between hospitals. Abstraction by a dedicated team for SEP-1 can reduce variability and improve efficiency.


End-organ function in patients on long-term circulatory support with continuous- or pulsatile-flow assist devices.
Limited data exist about the long-term effects of continuous-flow vs pulsatile-flow left ventricular assist devices (LVADs) on end-organ function. We reviewed the data of patients who underwent LVAD implantation at our institution between 1989 and 2004 and who were supported for >6 months. The continuous-flow (C-LVAD) group included 12 patients bridged to transplant with either a Jarvik 2000 or a Thoratec HeartMate II LVAD. The pulsatile (P-LVAD) group included 58 patients supported by a Thoratec HeartMate I LVAD. Follow-up was up to 15 months after LVAD implantation. Average duration of LVAD support was 370 +/- 182 days (range 180 to 754) for the C-LVAD group and 315 +/- 111 days (range 180 to 1,334) for the P-LVAD group. Patients from both groups were comparable for age, gender, body weight, cardiac index, ejection fraction, creatinine, blood urea nitrogen, creatinine clearance, albumin, total bilirubin, and transaminase levels before implantation. C-LVAD patients had a lower pre-operative hemoglobin than did P-LVAD patients (10.5 +/- 1.7 g/dl vs 12.2 +/- 1.9 g/dl; p = 0.01). In both groups, albumin, blood urea nitrogen, creatinine, creatinine clearance, total bilirubin, and transminase levels either improved or stayed within the normal range at 6, 9, 12, and 15 months after LVAD implantation. Four of the 12 C-LVAD patients and 28 of the 58 P-LVAD patients underwent cardiac transplantation. Actuarial survival, censored for transplant, at 9, 12, and 15 months was 90% for the C-LVAD group and 88%, 78%, and 74% for the P-LVAD group (p = not statistically significant). On the basis of these data, it appears that continuous- and pulsatile-type LVADs provide adequate blood flow to maintain proper end-organ function during prolonged circulatory support.


Effectiveness and safety of local anesthetic, semi-flexible pleuroscopy - experience from a peripheral hospital.
If the seemingly less invasive semi-flexible pleuroscopes are combined with strategies of conscious sedation and local anesthesia the pleuroscopy has the potential to reach an increasing number of hospital settings. Local experiences can provide valuable information pertaining to the reproducibility of this technique in different scenarios. We performed a retrospective analysis of the clinical records of all patients that had undergone local anesthetic semi-flexible pleuroscopy in our unit between February 2015 and July 2017. Data on demographics, previous biochemical, cytological and histopathological analysis, procedure details, diagnostic and therapeutic results, complications and mortality were collected from all patients. Statistical analysis was performed using SPSS v23. A total of 30 patients were included. They were mainly male (66.7%), with a median age of 72 years (minimum 19 years, maximum 87 years). All presented with exudative pleural effusions and the exam was performed for diagnostic reasons. Pleural tissue was obtained in all patients and the overall diagnostic accuracy was 93.3%. Malignancy was the chief group of diagnosis (66.7%), followed by pleural tuberculosis (13.3%). The procedure was well tolerated and self-limited subcutaneous emphysema was the only complication registered (13.3%). No deaths were associated with the procedure. Our results globally overlap those of wider series and reinforce the perception that local anesthetic semi-flexible pleuroscopy is a well-tolerated, safe and highly accurate diagnostic and therapeutic tool which has proved to be both feasible and effective in our experience.


Implementing a student practicum within a WIC program.
This article describes the efforts of the Larimer County Health Department's WIC program to expand nutrition services by developing a student practicum experience. Nutrition students from Colorado State University have successfully participated in WIC clinics providing individualized and group counseling sessions.


A case of diffuse nodular lymphoid hyperplasia.
Diffuse nodular lymphoid hyperplasia represents a rare disease that is grossly characterized by the presence of numerous visible mucosal nodules measuring up to, and rarely exceeding, 0.5 cm in diameter. These may involve the entire small intestine, the large intestine, or both. The etiology is unknown. When diffuse nodular lymphoid hyperplasia is found predominantly in the colon, it can mimic a variety of polyposis syndromes and this may cause difficulties in diagnosis. The disease may be associated with other pathologies, especially gastrointestinal malignancies. This causes controversy when deciding the treatment options. Following patients without any treatment may lead to malignant progression, while surgical treatment may result in unnecessary radical resections because of obscurity in the diagnosis. We report here a diffuse nodular lymphoid hyperplasia case who underwent a radical resection because of obscurity in the diagnosis.


Extended soft X-ray emission spectroscopy: quantitative assessment of emission intensities.
Soft X-ray emission spectroscopy (SXES) in the energy range between 150 eV and 1500 eV has typical attenuation lengths between tens and a few hundred nanometres. In this work the transmission of soft X-rays in synchrotron-based SXES has been quantitatively analysed using specially prepared layer samples. The possibility of extending the standard qualitative analysis of SXES by exploiting the information underlying the emission intensity was examined for thin layer structures. Three different experiment series were accomplished with model layer systems based on different sulfur-containing substrates: (i) MoS(2), (ii) CuInS(2), (iii) Cu(In,Ga)(S,Se)(2). The absorption of the S L(2,3) emission line by ZnO cover layers of up to 80 nm thickness was monitored and compared with theoretical expectations. By comparison with a reference intensity recorded from a bare substrate, the attenuation of the S L(2,3) emission could be used to accurately determine the ZnO overlayer thickness up to a critical thickness, depending on the set-up and the net S L(2,3) emission intensity. The results from these local energy-resolved spot measurements were compared with spatially resolved scans of the integral S L(2,3) emission intensity over areas of several mm(2). In the scan images the attenuation of the S L(2,3) emission intensity clearly reflects the local ZnO layer thickness. From the attenuation the ZnO layer thicknesses were calculated and compared with ellipsometric measurements and were found to be in excellent agreement. These results demonstrate the benefits of a quantitative analysis of SXES, making it an even more powerful tool for examining buried interfaces and for monitoring lateral inhomogeneities.


Mass spectrometry for proteomics-based investigation using the zebrafish vertebrate model system.
The zebrafish (Danio rerio) is frequently being used to investigate the genetics of human diseases as well as resulting pathologies. Ease of both forward and reverse genetic manipulation along with conservation of vertebrate organ systems and disease causing genes has made this system a popular model. Many techniques have been developed to manipulate the genome of zebrafish producing mutants in a vast array of genes. While genetic manipulation of zebrafish has progressed, proteomics have been under-utilized. This review highlights studies that have already been performed using proteomic techniques and as well as our initial proteomic work comparing changes to the proteome between the ascl1a-/- and WT intestine.


Automated access to a large medical dictionary: online assistance for research and application in natural language processing.
Online dictionaries can be important tools for research and application in natural language processing. This paper describes work with a machine-readable version of "Dorland's Illustrated Medical Dictionary". First the characteristics of the dictionary are briefly described, and then the complex process of converting the tape to an online interactive dictionary is discussed. The results of several experiments in automatically deriving information from the online dictionary are presented, and the paper ends with a discussion of the use of the online dictionary as a tool in the development of a natural language processing system designed for the biomedical domain.


Donor strand complementation governs intersubunit interaction of fimbriae of the alternate chaperone pathway.
Fimbrial filaments assembled by distinct chaperone pathways share a common mechanism of intersubunit interaction, as elucidated for colonization factor antigen I (CFA/I), archetype of enterotoxigenic Escherichia coli (ETEC) Class 5 fimbriae. We postulated that a highly conserved beta-strand at the major subunit N-terminus represents the donor strand, analogous to interactions within Class I pili. We show here that CFA/I fimbriae utilize donor strand complementation to promote proper folding of and interactions between CFA/I subunits. We constructed a series of genetic variants of CfaE, the CFA/I adhesin, incorporating a C-terminal extension comprising a flexible linker and 10-19 of the N-terminal residues of CfaB, the major subunit. Variants with a donor strand complement (dsc) of >or= 12 residues were recoverable from periplasmic fractions. Genetic disruption of the donor beta-strand reduced CfaE recovery. A hexahistidine-tagged variant of dsc19CfaE formed soluble monomers, folded into beta-sheet conformation, displayed adhesion characteristic of CFA/I, and elicited antibodies that inhibited mannose-resistant haemagglutination by ETEC expressing CFA/I, CS4 and CS14 fimbriae. Immunoelectron microscopy indicated that CfaE was confined to the distal fimbrial tip. Our findings provide the basis to elucidate structure and function of this class of fimbrial adhesins and assess the feasibility of an adhesin-based vaccine.


PEGylation-aided refolding of globular adiponectin.
Globular adiponectin (GAD) as the active domain of adiponectin is a promising candidate for anti-diabetic drug development. The recombinant production of GAD in Escherichia coli, however, is difficult because it is mainly expressed as inclusion bodies which need to be refolded to regain function. In this study we developed a novel method for refolding of GAD with a high efficiency by using polyethylene glycol (PEG) conjugation. An artificially designed DNA sequence encoding for GAD was synthesized and inserted into the pET28a vector to construct an expression plasmid which was thereafter transformed into E. coli BL21 (DE3) host cells for heterologous expression. After bacterial cell culture employing auto-induction medium, the inclusion bodies were collected, washed and dissolved in guanidine hydrochloride before PEG conjugation. Then the PEG-conjugated GAD was refolded by dialysis and purified by two steps of chromatography. The refolded conjugate showed a marked glucose-lowering activity in mice, demonstrating that it had been successfully refolded. As a convenient method, PEGylation-aided refolding could also be tested on other proteins to explore its suitability.


Optic nerve hypoplasia with good visual acuity and visual field defects: a study of children of diabetic mothers.
Seventeen children, born of severely diabetic mothers, exhibited segmental optic nerve hypoplasia with normal visual acuity and altitudinal or sector field defects corresponding to the hypoplastic areas of the disc. This is the first group of patients with optic nerve hypoplasia in which a possible cause has been identified. Optic nerve hypoplasia is neither a rare abnormality usually associated with serious central nervous system defects, nor is it always accompanied by decreased visual acuity.


New type of metalloproteinase inhibitor: design and synthesis of new phosphonamide-based hydroxamic acids.
A series of phosphonamide-based hydroxamate derivatives were synthesized, and the inhibitory activities were evaluated against various metalloproteinases in order to clarify its selectivity profile. Among the four diastereomeric isomers resulting from the chirality at the C-3 and P atoms, the compound with a (R,R)-configuration both at the C-3 position and the phosphorus atom was found to be potently active, while the other diastereomeric isomers were almost inactive. A number of (R,R)-compounds synthesized here exhibited broad spectrum activities with nanomolar K(i) values against MMP-1, -3, -9, and TACE and also showed nanomolar IC(50) values against HB-EGF shedding in a cell-based inhibition assay. The modeling study using X-ray structure of MMP-3 suggested the possible binding mode of the phosphonamide-based inhibitors.


Optical superresolution and visual hyperacuity.
Classically, diffraction theory sets a boundary for the resolving capacity of optical instruments. Yet some visual thresholds have values much better than the traditional resolution limit. Recent developments in superresolution, an area of optical physics and engineering with claims of transcending the stated resolution limits of optical instruments, are reviewed and their possible relevance to visual spatial processing and to the exploration of the eye's structure are assessed. In optical or diffractive superresolution the transmitted spatial-frequency band is not so much extended as either multiplexed with or displaced into regions that are usually beyond reach, with no overall gain in information transfer because prior knowledge is used to make inferences of possible object structure from the image. The Uncertainty Principle for photon position and momentum is never disobeyed. The study of the neural substrate of visual hyperacuity does, however, overlap that of "geometrical superresolution," in which techniques are used for transcending limits imposed by the receptor lattice in analyzing fine image structure.


Functional hemodynamic testing in pregnancy: recommendations of the International Working Group on Maternal Hemodynamics.
In the general population, functional hemodynamic testing, such as that during submaximal aerobic exercise and isometric handgrip, and the cold pressor test, has long been utilized to unmask abnormalities in cardiovascular function. During pregnancy, functional hemodynamic testing places additional demands on an already stressed maternal cardiovascular system. Dysfunctional responses to such tests in early pregnancy may predict the development of hypertensive disorders that develop later in gestation. For each of the above functional hemodynamic tests, these recommendations provide a description of the test, test protocol and equipment required, and an overview of the current understanding of clinical application during pregnancy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.


The prevalence of dengue virus in Brunei Darussalam during January-November 2010.
The aim of this study was to retrospectively determine the prevalence of dengue virus from April 2010 to November 2010 in Brunei Darussalam. A total of 250 serum samples from dengue diagnosed patients were examined. All serum samples were tested for dengue IgM and IgG antibodies and dengue NS1 antigen using the PanBio dengue ELISA commercial kit. To determine the prevalence of dengue virus serotype in the country, serotyping was performed for the 14 samples that were positive for NS1 antigen. Dengue virus serotyping was carried out using the conventional reverse transcriptase-polymerase chain reaction (RT-PCR). Of the 250 serum samples included in the study, 196 were laboratory dengue confirmed cases. Dengue virus serotype 1 (DENV-1) was the predominant circulating serotype, followed by DENV-3 and DENV-2. This is the first report of DENV-3 isolation in Brunei Darussalam.


Phosphorus and Yttrium Codoped Co(OH)F Nanoarray as Highly Efficient and Bifunctional Electrocatalysts for Overall Water Splitting.
Rational design and synthesis of bifunctional electrocatalysts with high efficiency and low-cost for overall water splitting is still a challenge. A simple approach is reported to prepare a phosphorus and yttrium codoped cobalt hydroxyfluoride (YP-Co(OH)F) nanoarray on nickel foam, which displays high-performance for both hydrogen evolution reaction (HER) and oxygen evolution reaction in alkaline solution. The codoping of yttrium and phosphorus into Co(OH)F leads to a tuned electronic environment and favorable electron transfer, thus resulting in superior water splitting activity. The YP-Co(OH)F electrode only requires an overpotential of 238 mV to reach a current density of 10 mA cm-2 (η10 ), much smaller than RuO2 (302 mV). Moreover, it displays an overpotential of 55 mV at η10 for HER, similar to that of Pt/C. When YP-Co(OH)F is used as both anode and cathode in a two-electrode configuration, it only demands a cell potential of 1.54 V at η10 , lower than the IrO2 ||Pt/C couple (1.6 V) as well as other recently reported electrocatalysts. It even maintains stable water splitting for 300 h. Such a two-electrode device can be easily driven by a 1.5 V silicon solar cell in sunlight, proving the potential of the promising catalyst for large-scale electrolytic water splitting.


Dexamethasone downregulates SIRT1 and IL6 and upregulates EDN1 genes in stem cells derived from gingivae via the AGE/RAGE pathway.
To evaluate the effects of dexamethasone on the aging of mesenchymal stem cells from human gingiva using next-generation sequencing. Four mRNAs were upregulated and 12 were downregulated when the results of dexamethasone at 24 h were compared with the control at 24 h. Expressions of SIRT1 and IL6 were decreased in dexamethasone at 24 h but expression of EDN1 was increased. Application of dexamethasone reduced the expression of SIRT1 and IL6 but enhanced the expression of EDN1 of stem cells.


Detection of luciferase gene sequences in nonluminescent bacteria from the Chesapeake Bay.
A 745-bp luxA fragment was amplified from Vibrio harveyi (UM 1503), radiolabeled, and used as a probe to detect and quantify luxA genotypes in culturable bacterial populations from the Chesapeake Bay. DNA samples from 53 reference strains were also examined for this gene. The luxA-positive bacteria comprised from 0-6% of the culturable heterotrophic bacterial community in samples from the Bay. Only those reference strains known to be luminescent contained the luxA gene, as indicated by PCR. Results in all cases were confirmed by PCR of DNA extracts and Southern hybridization analyses, using an internal probe for confirmation of luxA amplification products. Sequence analysis of luxA genes from three nonluminescent bacteria isolated from the Chesapeake Bay indicated little or no differences when compared with luxA sequences from known marine luminescent bacterial species. These three Chesapeake Bay strains and other luxA-positive strains were tested with a luminometer and confirmed to be nonluminescent. All of over 7800 bacterial colonies enumerated during this study from Chesapeake Bay samples were non-visibly luminescent. Our results indicate that luxA-positive bacteria isolated from the Chesapeake Bay are not generally luminescent on phenotypic examination, implying that gene probe techniques are required for examining luxA gene distribution in microbial populations present in environmental samples.


Impact of different betalactam antibiotics on the normal human flora, and colonization of the oral cavity, throat and colon.
Phenoxymethylpenicillin was given orally in doses of 800 mg twice daily for seven days to six patients, and bacampicillin was given in doses of 400 mg three times per day for seven days to another six patients. Saliva, throat and faecal specimens were taken for cultivation of aerobic and anaerobic bacteria. Only small changes in the normal saliva and throat flora were observed, and no changes in the faecal flora were noticed during the observation period. Cefoxitin was administered parenterally in doses of 2 g at 6 h intervals for 12 h to six other patients. Pronounced changes in the colon flora occurred. Of the aerobic bacteria, enterobacteria decreased and cefoxitin-resistant enterococci increased in number; of the anaerobic bacteria, gram-negative rods decreased in number. At the end of the administration period, all cefoxitin-resistant strains decreased, and suppressed enterobacteria and bacteroides increased in number.


Renal impairment among acute hospital admissions in a rural Ethiopian hospital.
Acute renal injury (AKI) is a relatively common clinical condition, reported to be associated with high rates of in-hospital mortality. Although here is an extensive literature on the nature and consequence of AKI in the developed World, much less is known in the developing World and more specifically in sub-Saharan Africa, which is addressed directly in this study. We describe the prevalence, clinical characteristics and impact of AKI in patients admitted to a single centre in Ethiopia with no dedicated renal services. Renal function tests are not preformed routinely in many Ethiopian hospitals. This occurred in 32% of all patients in this study, falling to 23% on surgical wards. As a consequence no cases of AKI were identified in the context of surgical admissions. AKI was only identified in a cohort of patients on medical wards, with a prevalence of roughly 20% of medical patients in which renal function was measured. The patients with AKI were younger than those at risk of AKI in studies from the developed World but were older than those who did not develop AKI in this study. In the majority of cases AKI could be considered to be pre-renal in its origin. In contrast to studies in the developed World, AKI did not adversely impact on either duration of hospital stay or on patient mortality. Residual renal impairment was, however, common at the point of discharge. The data suggest subtle differences in the nature and impact of AKI between those published and mainly derived from the developed world and patients in sub-Saharan Africa.


Catheter Assisted Management of Massive Pulmonary Embolism.
Pulmonary thromboembolism is common and missed by clinicians. We report a case of massive pulmonary embolism which was life threatening treated by the catheter assisted technique. Anticoagulation is the mainstay of therapy for most patients, with thrombolytic therapy reserved for some patients.1 Recent studies have suggested a role for systemic or catheter-directed thrombolytic therapy in selected patients.2 We present a case of a patient who presented with an PE, was successfully treated with catheter-directed thrombolysis.


The Swedish epidemic of coeliac disease explored using an epidemiological approach--some lessons to be learnt.
Sweden has experienced an epidemic of symptomatic coeliac disease that has no likeness anywhere else in the world. This is quite unique for a disease that is genetically dependent, immune-mediated and chronic, and suggests an abrupt increase and decrease, respectively, of one or a few causal factors influencing a large proportion of Swedish infants during the period in question. We have shown that half of the epidemic was explained by an increase in the proportion of infants introduced to gluten in comparatively large amounts after breast-feeding had been ended. This was partly an effect of societal changes in national dietary recommendations and the food content of industrially produced infant foods. Thus, these changes over time in infant feeding practices had a large public health impact. In fact, when the Swedish epidemic began, the increase in incidence rate was larger in girls than in boys, as was the decrease during the post-epidemic period. Moreover, children born during summer had an increased risk for coeliac disease, possibly as they were mostly introduced to dietary gluten during winter when infections are more common. Notably, birth cohorts of the epidemic and post-epidemic periods differ considerably regarding coeliac disease occurrence at comparable ages, even when followed up to school age. A longer follow-up will reveal to what extent new cases develop later in life, and to what extent this difference in cumulative incidence remains. However, mass screening studies of both the epidemic and post-epidemic cohorts at comparable ages are also planned to determine to what extent 'silent' disease cases develop. Continuing to explore the Swedish epidemic of coeliac disease by means of an epidemiological approach provides a unique opportunity. This may include increasing our understanding of what determines the clinical expression of the disease, exploring the potentially causal role of environmental exposures, and possibly also identifying strategies for primary prevention.


Peripheral blood erythroid progenitors from patients with sickle cell anemia: HPLC separation of hemoglobins and the effect of a HbF switching factor.
We describe the use of HPLC for the separation and quantitation of hemoglobin and globin chains. Utilization of this sensitive technique allows the analysis of hemoglobin and globin chains in the total accumulated and newly synthesized hemoglobin. Using this methodology, we have studied the effect of a previously described HbF factor in fetal calf serum on peripheral blood BFUe-derived erythroblasts from patients with sickle cell anemia. As in previous studies of peripheral blood BFUe-derived erythroblasts from hematologically normal adults, this HbF factor promoted the increased synthesis of HbF in the BFUe-derived erythroblasts from the sickle cell anemia patients.


PPAR-gamma agonists induce the expression of VEGF and its receptors in cultured cardiac myofibroblasts.
Myofibroblasts (myoFb) are the major cell types that appear at the site of myocardial infarction (MI) in response to injury and play a vital role in tissue repair/remodeling. Since vascular endothelial growth factor (VEGF) plays a crucial role in the infarcted/ischemic heart, we hypothesized that activation of the peroxisome proliferator-activated receptor (PPAR)-gamma by its agonists induces VEGF expression while simultaneously decreasing inflammation (NF-kappaB). Such an increase in myoFb VEGF expression by PPAR-gamma agonists may play a role in angiogenesis. Rat myoFb were treated with PPAR-gamma agonists and VEGF expression was measured by ELISA. The effect of these agonists on VEGF receptors was determined by qRT-PCR and flow-cytometric analysis. VEGF produced by these cells was also used for analysis of in vitro tubule formation (Matrigel assay). The PPAR-gamma activators troglitazone (TZ) and 15-deoxy-prostaglandin J2 (15J2) induced the expression of VEGF and its receptors (Flt-1 and KDR) in myoFb. TZ and 15J2 elicited a significant increase in the expression of KDR (14.7+/-1.0% and 9.6+/-2.1% respectively) and Flt-1 (24.5+/-2.0%, and 14.0+/-2.2% respectively) when compared to untreated myoFb. MyoFb treated with PPAR-gamma agonists increased extracellular VEGF, augmenting tubule formation on a Matrigel. The PPAR-gamma activator 15J2 significantly decreased the NF-kappaB activity in myoFb. This study demonstrates the induction of the VEGF accompanied by a reduction of NF-kappaB activity (inflammatory signaling) by PPAR-gamma agonists in cardiac myoFb. These results may further the understanding of the beneficial effects of PPAR-gamma agonists on infarcted tissue repair and angiogenesis.


Efficacy of Different Surface Treatments for Intraoral Repair of Veneered Zirconia Frameworks.
To evaluate the efficacy of different surface treatments on the repair of veneered zirconia ceramics. Forty-eight zirconia disks were divided into three groups according to the method of surface treatment: polished surface, air abraded, or ground using a special silicon carbide bur (SiC Grinding Bur). All specimens were primed using a primer containing MDP (Cimara Zircon, Voco) and then bonded to composite in Plexiglas tubes using dual-curing adhesive resin (Bifix QM, Voco). Each of the three groups was further divided into two subgroups (n = 8) stored either in water at 37°C for 3 days without thermocycling or stored in water at 37°C for 150 days with an additional 37,500 thermocycles between 5°C and 55°C. After storage, tensile bond strength (TBS) was measured in a universal testing machine. After 3 days of storage, silicon carbide bur and air-abraded groups showed high TBS that ranged from 32.7 to 41.0 MPa (p ≤ 0.05). After 150 days of storage with thermocycling, the air-abraded group showed the most durable TBS (34.8 MPa), while the silicon carbide bur group showed a significant reduction in TBS (21.2 MPa); in the polished control group, specimens all debonded spontaneously during storage (p ≤ 0.05). Repair of zirconia ceramic after chipping of its veneers showed durable TBS when surface conditioning with air abrasion or roughening of the zirconia surface with a silicon carbide bur was provided.


"Virtual rat": a tool for understanding hormonal regulation of gastrointestinal function.
This manuscript describes a "dry laboratory" using the "virtual rat" to help students understand the hormonal regulation of gastrointestinal function. The laboratory was modeled after a recent exercise that used the virtual rat to teach basic endocrine physiology. The virtual rat concept avoids the many obstacles associated with animal experimentation (for example, lack of adequate animal facilities, expense, equipment, and limited teacher experience). Our goal was to create a fun and educational experience while avoiding the complications associated with laboratory experimentation. No additional materials are required to complete this exercise. After finishing this laboratory, the students should have a greater understanding and appreciation for experimental design and the collection, analysis, and interpretation of data.


The effect of a surgical lubricant on in vivo sperm penetration of cervical mucus.
The implications of these data is that coital lubricants may impair fertility of some couples. Unfortunately, conception was not an end point on this study, and our conclusions must be considered inferential. Nevertheless, the results from this study lead us to recommend avoidance of surgical lubricants by couples attempting pregnancy.


[Osteoma of the sphenoid sinus--report of two cases].
Although osteoma of the paranasal sinus is comparatively common, involvement of the sphenoidal sinus region is extremely rare. Lame reported that a total of twelve cases had been described in the European literature since 1800. Mikaelin, Kulczynski and Dolan, since then, described three cases. This paper deals with two surgical cases of sphenoidal sinus osteoma, reviewing literature on paranasal sinus osteoma and differential diagnosis in the sphenoidal sinus lesion. Case 1. A 20-year-old man was referred to us by an ophthalmologist, complaining of left visual disturbance (visual acuity: 0.02). He had a past history of chronic sinusitis. Neurological examination revealed papilledema on the left. Plain skull X-ray film showed marked destruction of the sphenoidal sinus and tomography demonstrated thinning and expanding of the sella floor with cloudiness in the sphenoidal sinus. CT scan showed an irregular high density mass in the sphenoidal sinus. Sublabial-nasoseptal sphenoidotomy was performed. The sinus was occupied by homogeneous osseous tissue surrounded by thin fibrous tissue. The osseous part was removed as much as possible by a high speed air drill. Histopathologic examination confirmed mature osteoma. Postoperative course was uneventful and left visual acuity was improved up to 0.06. He is now doing well without recurrence for six months. Case 2. A 59-year-old woman was admitted to our hospital, complaining of acromegaly for ten years. She had a past history of chronic sinusitis, hypertension, diabetes mellitus and left putaminal hemorrhage which was evacuated five months before. She had typical acromegalic features and serum levels of growth hormone was 65.8 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)


The relationship between sperm morphology and chromatin integrity in the koala (Phascolarctos cinereus) as assessed by the Sperm Chromatin Dispersion test (SCDt).
Koala (Phascolarctos cinereus) sperm nuclei show a tendency to swell after cryopreservation, but it is uncertain whether this phenomenon is associated with DNA fragmentation. In this study, we validated a modified version of the sperm chromatin dispersion test (SCDt) for use with koala spermatozoa, which is the first use of the test for a marsupial. Cryopreserved spermatozoa (multiple straws) from a single koala were used to explore the relationship between sperm morphology, viability, chromatin dispersion, and DNA fragmentation. A SCDt prototype kit (Sperm Halomax) was specifically developed for koala spermatozoa with the use of a lysing solution that did not contain dithiothreitol. DNA fragmentation of lysed and nonlysed spermatozoa was examined in microgel slides and validated by means of in situ nick translation (ISNT). The SCDt was then applied to the analysis of extended and frozen-thawed semen samples of 3 different koalas. Spermatozoa were classified into 3 distinct koala sperm morphotypes (KSMs) after the SCDt: 1) KSM-1, rod-shaped cells with no halo of DNA; 2) KSM-2, rounded nuclei with various degrees of halo formation about a dense chromatin core; and 3) KSM-3, rod-shaped or rounded nuclei consisting of an inner chromatin core but with large dispersed halos of stellar chromatin. Although ISNT after the SCDt did not label KSM-1, both KSM-2 and KSM-3 stained positively for DNA fragmentation. ISNT was not able to differentiate between KSM-2 and KSM-3. Although application of the SCDt to the spermatozoa of another 3 koalas showed no difference in the percentage of the 3 sperm morphotypes found between extended and frozen-thawed semen, thawed spermatozoa incubated at 35 degrees C for 2 hours showed an increase in the incidence of KSM-3 and a corresponding decrease in KSM-2. We propose that KSM-1 and KSM-2 represent nuclei that show either no, or only limited, sperm DNA fragmentation, respectively. It is likely that the halos formed around KSM-2 are from DNA that is damaged as part of the normal processing of the spermatozoa and is a consequence of the lack of cysteine residues and associated stabilizing disulfide bonds in marsupial sperm DNA. "True" sperm DNA damage is most likely associated with KSM-3, which shows a massive dispersion of chromatin similar to that described in other species. A model of koala sperm chromatin structure is proposed to explain the behavior of the sperm nuclei after the SCDt. Further studies are required to determine whether DNA damage found in KSM-2 is indicative of single-stranded DNA breakage associated with an inherent lack of cysteine residues in marsupial sperm chromatin. Conversely, it will also be important to establish whether KSM-3 is caused by an increased incidence of double-stranded DNA breakage and whether this abnormality is correlated with impaired fertility as it is in other species.


High incidence of BK virus large-T-antigen-coding sequences in normal human tissues and tumors of different histotypes.
T-antigen (TAg) coding sequences specific for BK virus (BKV) were detected, by PCR amplification followed by Southern-blot hybridization, in a high percentage of human tumors and tumor-cell lines, as well as in normal tissues, by analysis of 189 specimens. Specifically, the BKV early region was detected in 85% of brain tumors and in all normal brain tissues, in 78% of osteosarcomas, in 38% of Ewing's tumors, in 40% of normal bone specimens and in 71% of normal peripheral blood cell samples. Wilms' tumor tissues used as a control were all negative for BKV sequences. RT-PCR analysis indicated that TAg coding sequences were expressed in specimens carrying BKV early region, ranging from 64% of the osteosarcomas to 100% of glioblastomas, Ewing's tumors, peripheral blood cells and normal bone. Moreover, DNA sequencing performed in 12 different positive samples revealed that the amplified PCR products are identical to the early-region sequence of wild-type BKV. The role of BKV TAg and its possible mechanism of action in human tumorigenesis are discussed.


Analysis of the survival of mature human eosinophils: interleukin-5 prevents apoptosis in mature human eosinophils.
We and other groups have previously shown that interleukin-5 (IL-5) maintained the viability of mature eosinophils in an in vitro liquid culture system. Mature eosinophils did not proliferate but their survival was maintained in the presence of IL-5. Using this culture system, we investigated the mechanism of IL-5-mediated survival. In the absence of human IL-5 (hIL-5) mature eosinophils succumbed after 4 days, while in the presence of hIL-5 they survived up to 10 days. When DNA extracts of cultured eosinophils were analyzed on an agar gel electrophoresis, marked DNA fragmentation was observed in the absence of hIL-5, while no significant DNA fragmentation was observed in the culture with hIL-5 for 48 hours. The DNA fragmentation appeared as early as 6 to 12 hours after hIL-5 deprivation. Concomitantly, IL-5 stimulated total RNA and protein synthesis, but did not induce DNA synthesis in mature eosinophils. Because cycloheximide or actinomycin D impeded the protection of apoptosis by hIL-5, some new RNA and protein synthesis appeared to be required in this phenomena. These findings indicate that IL-5 maintains survival of mature eosinophils with induction of new RNA and protein synthesis, thus leading to the inhibition of apoptosis.


Towards quantification of toxicity of lithium ion battery electrolytes - development and validation of a liquid-liquid extraction GC-MS method for the determination of organic carbonates in cell culture materials.
A novel method based on liquid-liquid extraction with subsequent gas chromatography separation and mass spectrometric detection (GC-MS) for the quantification of organic carbonates in cell culture materials is presented. Method parameters including the choice of extraction solvent, of extraction method and of extraction time were optimised and the method was validated. The setup allowed for determination within a linear range of more than two orders of magnitude. The limits of detection (LODs) were between 0.0002 and 0.002 mmol/L and the repeatability precisions were in the range of 1.5-12.9%. It could be shown that no matrix effects were present and recovery rates between 98 and 104% were achieved. The methodology was applied to cell culture models incubated with commercial lithium ion battery (LIB) electrolytes to gain more insight into the potential toxic effects of these compounds. The stability of the organic carbonates in cell culture medium after incubation was studied. In a porcine model of the blood-cerebrospinal fluid (CSF) barrier, it could be shown that a transfer of organic carbonates into the brain facing compartment took place. Graphical abstract Schematic setup for the investigation of toxicity of lithium ion battery electrolytes.


High hydrostatic pressure and UV light treatment of produce contaminated with Eimeria acervulina as a Cyclospora cayetanensis surrogate.
The prevalence, size, genome, and life cycle of Eimeria acervulina make this organism a good surrogate for Cyclospora cayetanensis, a protozoan that causes gastroenteritis in humans, including recent outbreaks in the United States and Canada associated with contaminated raspberries and basil. Laboratory studies of C. cayetanensis are difficult because of the lack of readily available oocysts and of infection models and assays. UV radiation and high-hydrostatic-pressure processing (HPP) are both safe technologies with potential for use on fresh produce. Raspberries and basil were inoculated with sporulated E. acervulina oocysts at high (10(6) oocysts) and low (10(4) oocysts) levels, and inoculated and control produce were treated with UV (up to 261 mW/cm2) or HPP (550 MPa at 40 degrees C for 2 min). Oocysts recovered from produce were fed to 3-week-old broiler chickens, which were scored for weight gain, oocyst shedding, and lesions at 6 days postinoculation. Oocysts exhibited enhanced excystation on raspberries but not on basil. Birds fed oocysts from UV-treated raspberries had reduced infection rates, which varied with oocyst inoculum level and UV intensity. Birds fed oocysts from UV-treated raspberries (10(4) oocysts) were asymptomatic but shed oocysts, and birds fed oocysts from UV-treated basil (10(4) oocysts) were asymptomatic and did not shed oocysts. Birds fed oocysts from HPP-treated raspberries and basil were asymptomatic and did not shed oocysts. These results suggest that UV radiation and HPP may be used to reduce the risk for cyclosporiasis infection associated with produce. Both treatments yielded healthy animals; however, HPP was more effective, as indicated by results for produce with higher contamination levels.


Interferon-gamma acts proapoptotic on hepatic stellate cells (HSC) and abrogates the antiapoptotic effect of interferon-alpha by an HSP70-dependant pathway.
The activated hepatic stellate cell (HSC) is an important fibrogenic cell type of the liver. Interferon-alpha (IFN-alpha) has recently been shown to elicit an antiapoptotic effect on activated HSC by a JAK-2-dependent inhibition of caspase-8 activation. As JAK-2 has so far been shown to be a member of the IFN-gamma signal transduction pathway we studied the effect of IFN-gamma on apoptosis as well as on its signaling in primary cultured rat HSC. IFN-gamma elicited a proapoptotic effect in activated HSC. The combination of both, IFN-gamma and IFN-alpha, however, completely cancelled each other's effect. No effect of the two cytokines on major members of apoptosis-regulating systems (CD95, CD95L, bcl-2, bax, bcl-xL, p53, p21WAF1, p27, NFkappaB) could be observed. Western Blot analysis revealed that gene expression of the chaperone HSP70 was found to be downregulated by IFN-gamma but upregulated by IFN-alpha. The effect could be abrogated by administration of both. After transfection of activated HSC with a pCMV-HSP70 M expression vector the proapoptotic effect of IFN-gamma was cancelled. Using HSP70 antisense, the antiapoptotic effect of IFN-alpha was cancelled as well. However IFN-gamma had no effect on upregulation of JAK-2 and pJAK-2 by IFN-alpha. Taken together IFN-gamma and IFN-alpha exert opposite effects on apoptosis in HSC. This effect is mediated by their counteracting effect on HSP70 expression which acts antiapoptotic at the level of caspase-8.


[Application prospect about bioremediation of polychlorinated biphenyls-contaminated soil with immobilized microorganism technique: a review].
As one type of the persistent organic pollutants, polychlorinated biphenyls (PCBs) are tremendously harmful to organisms. These compounds are easily absorbed onto soil particles and able to accumulate in soil after they are released into the environment. Bioremediation technology of PCBs-contaminated soils has become a research hotspot in recent years, and immobilized microorganism technique has high developing and applying value because of its unique advantages in environmental remediation. This paper reviewed the chief remediation technology of PCBs-contaminated soils and then analyzed the characteristics of immobilized microorganism technique and its research progress in remediation of organic polluted soil. Finally, the feasibility and problems of this technique in remediation of PCBs-contaminated soil were also discussed.


Crystal and molecular structure of adenosine 3',5'-cyclic phosphate.
The structure of adenosine 3',5'-cyclic phosphate has been determined by single-crystal x-ray diffraction. The two molecules in the asymmetric unit show different conformation about the glycosidic bond, while other structural details are essentially the same. The furanose rings are puckered with the C(4') atom out of the best four-atom plane. The bond lengths and angles appear to be normal.


Technologists' productivity when using PACS: comparison of film-based versus filmless radiography.
The objective of this study was to assess the impact of filmless operation and computed radiography on technologists' examination times compared with conventional film-based operation and film-screen radiography. Compared with conventional film-screen operation, filmless operation using computed radiography was associated with a significant decrease in technologist examination times in the performance of general radiographic examinations. This decrease in technologist examination times in a filmless environment offers the potential for increased productivity with resulting personnel savings and improved operational efficiency.


To study the healing art.
The present paper traces the careers of two men: Dominique, Baron Larrey, and Sir James McGrigor, and examines their contributions to military medicine in the Napoleonic period.


Small leucine-rich repeat proteoglycans associated with mature insoluble elastin serve as binding sites for galectins.
We previously reported that galectin-9 (Gal-9), an immunomodulatory animal lectin, could bind to insoluble collagen preparations and exerted direct cytocidal effects on immune cells. In the present study, we found that mature insoluble elastin is capable of binding Gal-9 and other members of the human galectin family. Lectin blot analysis of a series of commercial water-soluble elastin preparations, PES-(A) ~ PES-(E), revealed that only PES-(E) contained substances recognized by Gal-9. Gal-9-interacting substances in PES-(E) were affinity-purified, digested with trypsin and then analyzed by reversed-phase HPLC. Peptide fragments derived from five members of the small leucine-rich repeat proteoglycan family, versican, lumican, osteoglycin/mimecan, prolargin, and fibromodulin, were identified by N-terminal amino acid sequence analysis. The results indicate that Gal-9 and possibly other galectins recognize glycans attached to small leucine-rich repeat proteoglycans associated with insoluble elastin and also indicate the possibility that mature insoluble elastin serves as an extracellular reservoir for galectins.


After-contraction phenomenon: influences on performance and learning.
Three experiments investigated the influence of an after-contraction phenomenon on the performance and learning of a dynamic force-production task. The after-contraction effect refers to an involuntary potentiation (induced by a sustained precontraction) that is thought to summate with voluntary motor commands to bias subsequent responding. The precontraction involved a brief (20 s) static contraction. The subsequent influence of the precontraction on a dynamic force-production task was assessed. Experiments 1 and 2 were aimed at demonstrating the direct impact of the precontraction intensity on the magnitude and decay of the after-contraction effect. The results indicated that as the intensity of the precontraction increased, the magnitude of the induced bias increased. In Experiment 3, the indirect influence on subsequent retention of varying the precontraction intensity during acquisition was investigated. The results indicated that the performance of subjects experiencing varying precontraction intensities during acquisition was inferior to that of subjects experiencing a constant precontraction intensity, but the performance of the varied precontraction intensities group was superior on the test of retention. It is noted that the paradoxical reversal from acquisition to retention is similar to that found in contextual interference experiments and may arise from similar mechanisms.


The synthesis of a carbon-14 labeled pegylated Adnectin™ for placental transfer studies in guinea pigs.
Adnectins™ are novel fibronectin-based proteins containing domains engineered to bind to targets of therapeutic interest. The molecular weights of adnectins are less than conventional monoclonal antibodies but larger than traditional small molecules. Until now, there has been no information on the placental transfer of adnectins. To assess placental permeability to adnectins in pregnant guinea pigs, a radiolabeled adnectin, ATI-1072, bound to polyethylene glycol through a [(14) C]Maleimide linker, was synthesized from [1,4-(14) C]Maleic acid. This publication describes the synthesis and analysis of PEG-[(14) C]Maleimide-adnectin ([(14) C]ATI-1072).


Sealing the broken barrier in IBD: intestinal permeability, epithelial cells and junctions.
Inflammatory bowel diseases (IBD) are considered barrier diseases. After misleading initial results, the pathogenic importance of a disturbed mucosa is now widely accepted, largely because a certain percentage of first-degree relatives of patients with IBD do have permeability alterations, as assessed by oral markers. In the presence of a normal appearing gut mucosa, functional alterations of the highly dynamic inter-enterocyte tight junctions have to be considered to be responsible for the observed alterations. Indeed, various alterations of the transmembrane and intracytoplasmic proteins have been reported in IBD. An important therapeutic goal is to maintain disease remission by preservation of the correct organization of these complexes. Of the potential therapeutic approaches, the various anti-TNF agents are the best-studied agents, but other treatments may tighten the gut through as yet unknown mechanisms.


[Classification of oral contraceptives and its practical application to choice of prescriptions].
The authors have tried to classify the oral contraceptives at present in use throughout the world by their respective levels of oestrogenic and progestogenic components, taking into consideration also the relative strength of each product in use. They have based this classification on their personal experience of the several oral contraceptive products and on a profound study of the international literature. In this way it is possible to define a place for each oral contraceptive so that it can be chosen for the best possible use of a particular product for the hormonal background of the person using the contraceptive. It is true that changes have to be made to work out the oral contraceptives used for masses of people, but on the other hand in countries where there is sufficient medical personnel and education so that it is possible to think out and to prescribe for an individual, it seems to us useful that the doctor who is prescribing should try to adjust the oral contraceptive to the hormonal climate of the woman seeking it. This is true not only for the first time a prescription is made but in cases where by the accident of failure to tolerate the product something must be done to correct the troubles that are so often found in the first months after starting to use contraceptive products. This study includes a general picture of all oral contraceptives in which the products have been classified according to the total dose of oestrogens administered and according to the proportions of progesterone to oestrogens which make up the hormonal climate of the product. On the other hand this study also includes a list of the observations to make in order to adapt the oral contraceptive to the side-effects shown after the first prescription. The authors have come to the conclusion that by adapting the choice of a particular oral contraceptive to the woman who is to receive it interruptions in taking the contraceptive because of side-effects should be avoided. So unwanted pregnancies will be avoided and also the termination of these unwanted pregnancies.


Accelerated and high-quality Fourier ptychographic method using a double truncated Wirtinger criteria.
Fourier ptychographic microscopy (FPM) is a recently developed computational microscopy technique for wide-field-of-view and super-resolution complex imaging. Wirtinger-flow-based methods can effectively suppress noise and reduce data acquisition time, but they are time-consuming during the phase reconstruction. In this paper, we present a Wirtinger-flow-based reconstruction method for FPM, which combines the Poisson maximum likelihood objective function, improved truncated Wirtinger criteria, and improved adaptive momentum method. Both the simulation and experimental results demonstrate that the proposed method runs faster and the reconstruction quality is similar to or better than other state-of-the-art Wirtinger-flow-based methods.


U.S.: PEPFAR reauthorization bills pass House, Senate committee.
On 2 April 2008, the U.S. House of Representatives passed a bill (H.R. 5501) to reauthorize the President's Emergency Plan for AIDS Relief (PEPFAR). The House bill would authorize the appropriation of US$50 billion over the next five years--40 percent more than the US$30 billion requested by President George W. Bush.


Self-assembled lamellar nanostructures of wholly aromatic rod-rod-type block molecules.
Wholly aromatic rod-rod type di- and triblock molecules, oligo(ether sulfone)-b-oligo(ether ketone)s (OES-OEK), were synthesized to study a solid-state self-assembled nanostructure. The OES and OEK segments in the block molecules form segregated crystalline domains. The energy-filtering transmission electron microscopy images revealed that the di- and triblock OES-OEK co-oligomers formed lamellar nanostructures with a periodicity of approximately 9 and 13 nm, respectively. [structure: see text].


[Indicators of iron metabolism and cellular immunity in healthy children and in those with iron deficiency anemia in relation to ecological conditions].
The authors provide statistical data attesting to the fact that during the development of iron deficiency anemia in schoolchildren, the hematological, biochemical indicators characterizing iron metabolism in the body and phagocytic activity of peripheral blood leukocytes, one of the parameters of cellular immunity, undergo noticeable changes. It has been noted that in the regions where toxic chemicals are intensely used, both children with iron deficiency and normal ones demonstrate a significant decrease of phagocytic activity of leukocytes in spite of the fact that no quantitative alterations in iron metabolism are detectable in such a case.


Mitochondrial D-loop and coding sequence analysis using pyrosequencing.
In forensic casework analysis, mitochondrial deoxyribonucleic acid (DNA) often is used when the evidence material contains scarce amounts of DNA. Here, a mitochondrial DNA typing system for D-loop and coding region analysis based on pyrosequencing is described. Pyrosequencing is a real-time, single-tube sequencing-by-synthesis method, in which a cascade of enzymatic reactions yields detectable light. This pyrosequencing system has a higher resolution than the D-loop analysis performed routinely today as it also covers informative positions in the mitochondrial coding region. The system is composed of 16 polymerase chain reaction (PCR) fragments and 24 pyrosequencing reactions with a turn around time for a 96-well plate of less than 3 h after PCR.


Simultaneous energy generation and UV quencher removal from landfill leachate using a microbial fuel cell.
The presence of UV quenching compounds in landfill leachate can negatively affect UV disinfection in a wastewater treatment plant when leachate is co-treated. Herein, a microbial fuel cell (MFC) was investigated to remove UV quenchers from a landfill leachate with simultaneous bioelectricity generation. The key operating parameters including hydraulic retention time (HRT), anolyte recirculation rate, and external resistance were systematically studied to maximize energy recovery and UV absorbance reduction. It was found that nearly 50% UV absorbance was reduced under a condition of HRT 40 days, continuous anolyte recirculation, and 10 Ω external resistance. Further analysis showed a total reduction of organics by 75.3%, including the reduction of humic acids, fulvic acids, and hydrophilic fraction concentration as TOC. The MFC consumed 0.056 kWh m-3 by its pump system for recirculation and oxygen supply. A reduced HRT of 20 days with periodical anode recirculation (1 hour in every 24 hours) and 39 Ω external resistance (equal to the internal resistance of the MFC) resulted in the highest net energy of 0.123 kWh m-3. Granular activated carbon (GAC) was used as an effective post-treatment step and could achieve 89.1% UV absorbance reduction with 40 g L-1. The combined MFC and GAC treatment could reduce 92.9% of the UV absorbance and remove 89.7% of the UV quenchers. The results of this study would encourage further exploration of using MFCs as an energy-efficient method for removing UV quenchers from landfill leachate.


Influence of sample storage duration on serum protein profiles assessed by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF MS).
Issues have been raised concerning the robustness and validity of alleged serum markers discovered by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF MS). Pre-analytical variables have been shown to exert a profound effect on protein profiles, irrespective of true biological variation. However, little is known about the possible effects of sample storage duration on protein profiles. We, therefore, aimed to investigate the effects of extended storage duration on the serum protein profile. Archival sera from 140 breast cancer patients, stored at -30 degrees C for 1-11 years, were profiled by SELDI-TOF MS using immobilised metal affinity capture (IMAC) arrays, a condition applied in the majority of breast cancer biomarker discovery studies. Fourteen peak clusters, structurally identified as C3a des-arginine anaphylatoxin and multiple fragments of albumin and fibrinogen, were found to be significantly associated with sample storage duration by five distinct patterns. These proteins have been described previously as potential cancer markers, rendering them specific to both disease and sample handling issues. To prevent experimental variation being interpreted erroneously as disease associated variation, assessment of potential confounding pre-analytical parameters is a pre-requisite in biomarker discovery and validation studies. In addition, with respect to the different (non-)linear patterns observed in the current study, simply performing linear corrections to account for sample storage duration will not necessarily suffice.


Morphologic character of transforming renal cell cultures derived from Wistar rats given dimethylnitrosamine.
The morphologic character of kidney cells during serial subculture following isolation from Wistar rats treated several hours to 1 week previously with a carcinogenic dose of dimethylnitrosamine (DMN; 60 mg/kg body weight following protein deprivation) was compared with the appearance of cultures derived from normal control rats. Apart from early signs of cell toxicity, cultures from DMN-treated rats appeared similar to those from untreated rats for the first four passages. Control cells underwent senescence usually by subculture 4, whereas the test cultures survived to express morphologic transformation (usually at subculture 5) as dense macroscopic colonies of piled up cells. In 18 of the 20 test cultures, the cell populations that persisted in continuous culture following expression of morphologic transformation were exclusively mesenchymal, closely resembling DMN-induced renal mesenchymal tumor cells in continuous culture. In the remaining 2 test cultures from DMN-treated rats, a persisting population of abnormal epithelium was present in addition to morphologically transformed mesenchymal cells. The occurrence of populations of altered mesenchymal and epithelial cells characterized by prolonged survival in vitro following isolation from rats shortly after treatment with a carcinogenic dose of DMN was believed to be related to the long-term induction in the rat kidney of a high incidence of mesenchymal tumors and a lower incidence of cortical epithelial tumors by the same dose schedule.


A statistical study of ENoG test error.
Electroneurography (ENoG) is currently the most sophisticated and objective test available for assessing nerve degeneration in patients suffering from facial nerve paralysis. However, the test requires considerable experience before error due to intertest variability can be brought within reasonable limits. In a statistical study on normal participants, the error associated with two conventional recording techniques--optimized lead placement (OLP) and standardized lead placement (SLP)--was determined to be 17.8% and 20.7%, respectively. A significant increase in error was observed with the OLP approach (22.9%) if responses could not be monitored oscilloscopically, a common situation in patients with severe degeneration. In a final study, however, a previously unreported factor was found to significantly reduce test error: recording electrode size. In particular, unconventionally small recording electrodes (3 to 7 mm) produced as much as 4% less error when administering the technique.


Mortality studies of machining fluid exposure in the automobile industry. IV: A case-control study of lung cancer.
Machining fluids are diverse products that contain numerous additives and contaminants, including polycyclic aromatic hydrocarbons. Studies treating machining fluids as an aggregate exposure have found both positive and negative associations with lung cancer. In this nested case-control study of automotive workers (667 cases and 3,041 matched controls), individual estimates of exposure quantity and duration for specific classes of machining fluids were derived. An inverse dose-response relationship was found between synthetic machining fluids and lung cancer mortality, with an odds ratio of 0.6 (95% CI = 0.4, 0.8) for the highest level of lifetime exposure. The relationship was strongest for recent exposures. There was little evidence of an association with soluble or straight oil machining fluids. Risks were inconsistently elevated in workers exposed to aluminum. Results from this study provide strong evidence that exposure to machining fluids is not associated with an increased risk of lung cancer mortality in automotive workers.


Combined effects of dentin sialoprotein and bone morphogenetic protein-2 on differentiation in human cementoblasts.
The aim of this study is to determine the effects of the combination of recombinant human BMP-2 (rh-BMP-2) and dentin sialoprotein (rh-DSP) on growth and differentiation in human cementoblasts and determine the underlying signal transduction mechanism. Compared to treatment of cementoblasts with either rh-BMP-2 or rh-DSP alone, the combination of rh-BMP-2 and rh-DSP synergistically increased cell growth, ALP activity, nodule formation and expression of differentiation markers. The differentiation-promoting effect was also observed in periodontal ligament cells and an osteoblastic cell line. Likewise, combination of rh-DSP and rh-BMP-2 increased BMP-2 mRNA expression and Smad1/5/8 phosphorylation, which was blocked by the BMP antagonist noggin. The expression levels of α2β1 integrin and RhoA, as well as the phosphorylation status of FAK and Akt, were increased by the combination of rh-BMP-2 and rh-DSP in a time-dependent manner. In addition, rh-BMP-2 and rh-DSP enhanced expression of Wnt ligands, β-catenin activation and GSK-3β phosphorylation, all of which were inhibited by the Wnt receptor antagonist DKK1. Furthermore, treatment with rh-DSP plus rh-BMP-2 resulted in phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 and also induced the nuclear translocation of the NF-κB p65 subunit, which was blocked by noggin. This study demonstrates for the first time that rh-DSP and rh-BMP-2 act synergistically, enhancing each other's ability to stimulate cementoblastic cell growth and differentiation in vitro via autocrine BMP, integrin, Wnt/β-catenin, MAP kinase and NF-κB pathways. These results support the therapeutic potential of a combination strategy for aiding periodontal regeneration.


Treatment of bullous pemphigoid.
Bullous pemphigoid (BP) is the most frequent auto-immune blistering skin disease. Up to recently, it was treated with oral corticosteroids. High dose steroids are poorly tolerated in the elderly and probably contributed to the high mortality rates observed in several cohorts. For years, efforts have been devoted to looking for steroid sparing agents including immunosuppressive drugs, plasma exchanges, intravenous immunoglobulins, tetracycline. Many seemed useful in open series but proved ineffective or marginally effective when tested in randomized controlled trials. An important breakthrough was the demonstration by a large randomized trial that a "super-potent" topical corticosteroid (clobetasol propionate) was not only associated with a significant decrease in severe complications and mortality of BP patients but was also more effective than oral prednisone. New strategies for BP should include topical clobetasol propionate as the first line treatment and consider adjuvant therapy only in the very rare cases that are either resistant to or intolerant of this treatment.


The evaluation of the oxidant injury as a function of time following brain irradiation in a rat model.
This study presents the evaluation of the oxidant injury as a function of time following brain irradiation in a rat model. Thirty-five Wistar rats were divided into seven groups. The rats in Group 1 through Group 6 underwent irradiation, whereas the rats in Group 7 underwent sham irradiation. The rats in Group 1 through Group 6 underwent euthanasia at 1 through 48 h following irradiation, whereas the rats in Group 7 underwent euthanasia immediately following sham irradiation. At the time of euthanasia, the brain tissue was dissected for evaluation of the malondialdehyde (MDA) level and the superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHPX) activities. The mean MDA levels were increased and the mean SOD, CAT and GSHPX activities were decreased at all of the time points for evaluation for the rats that underwent irradiation as compared to the rats that underwent sham irradiation, substantial for Group 1 and gradually leveling out through Group 6. This study confirms that the oxidant injury is evaluated at its best through the first several hours following brain irradiation.


Wrist-ankle Acupuncture Increases Pain Thresholds in Healthy Adults.
Context • Wrist-ankle acupuncture (WAA) has been used to relieve both chronic and acute pain in China. Some research has shown that WAA can increase the pain thresholds in pain patients, but the ability of WAA to affect the pain thresholds in healthy adults is unknown. Objective • The study intended to assess the influence of WAA on the pain thresholds of healthy adults. Design • This is an observational study. Setting • This study was conducted in the School of Traditional Chinese Medicine at the Second Military Medical University (Shanghai, China). Participants • Participants were 50 healthy university students aged 19-23 y. Intervention • In the theory of WAA, each side of the body and each limb are longitudinally divided into 6 regions, with 1 needling point defined for each region at the wrist or ankle. The theory indicates that needling a point should relieve pain in a point's corresponding region. For the study, a needle was inserted and retained for 30 min in the Upper 2 point of the left wrist of each participant. Outcome Measures • The pressure pain threshold was measured by a handheld algometer at a position in the left Upper 2 region corresponding to the site of the needling and at positions in the right Upper 2 region as well as the left and right Upper 3 regions not corresponding to the site of the needling. The measurements were taken at 40 min before needling, 5 min after needling, 30 min after needling when the needles were removed, and 70 min after needling. Results • The immediate influence of the WAA on the pain threshold was not significant at 5 min after needling (P > .05). However, at 30 min after needling when the needles were removed, the increases in the pain thresholds were statistically significant when compared to those at 40 min before needling, which were the measurements at baseline (P ≤ .01). At 70 min after needling, the pain thresholds remained higher than those at 40 min before needling (P < .05). From 40 min before needling to 70 min after needling, the pain thresholds in the different positions showed a continuous increase. Conclusions • The WAA had an analgesic effect on pressure-induced pain not only in the corresponding but also in the noncorresponding regions of the needling point in healthy adults. The immediate analgesic effect of the WAA at 5 min after needling was not obvious, but the effects at 30 min and 70 min after needling were statistically significant.


Brønsted acid-catalyzed Mannich reaction through dual activation of aldehydes and N-Boc-imines.
In the presence of a Brønsted acid catalyst, both aldehydes and N-Boc-aminals were converted to enecarbamates and N-Boc-iminium salts as activated nucleophiles and electrophiles, respectively, giving unprecedented Mannich adducts. The asymmetric variant of the present Mannich reaction has also been demonstrated with a chiral phosphoric acid catalyst.


[Malignant melanoma in an ovarian dermoid cyst].
A case of patient that during a cesarean section, a dark zone of the Omentum was biopsied, and informated as melanosis. Then appeared a cystic mass in the left ovary, and an ooforectomy was performed, resulting a Primary Malignant melanoma.


Hormonal control of morphogenetic cell death of the wing hypodermis in Lucilia cuprina.
1. Cytoplasmic fragments in the haemolymph of newly emerged flies derive from the degenerating wing hypodermis. 2. At the time of eclosion, dorsal and ventral cell layers of the wing are connected by processes containing bundles of microtubules and microfilaments. Cytoplasmic fragments contain similar bundles of microtubules but few microfilaments. 3. Extensive vacuolation marks the onset of hormonally initiated fragmentation of the wing hypodermal cells. Haemocytes containing lysosomes are present in the wing at this time, but do not invade the fragmenting hypodermis.


Depression and CSF endorphin fraction I: seasonal variation and higher levels in unipolar than bipolar patients.
Radioreceptor assay of endorphin Fraction I in the cerebrospinal fluid (CSF) of 92 inpatients suffering from major depression revealed the following: (1) clearly elevated levels as compared to normal control subjects, (2) higher level in unipolar than in bipolar patients, and (3) seasonal rhythms showing peaks in early fall for unipolar patients and late fall for bipolar patients. The annual pattern observed bears some resemblance to the known seasonal variations in the incidence of affective disorders and suicide.


Spinal source for the synchronous fluctuations of bilateral monosynaptic reflexes in cats.
Successive stimuli of constant intensity applied to Ia afferents produce spinal monosynaptic reflexes (MSRs) of variable amplitude. We recorded simultaneous MSRs in the left and right L7 (or L6) ventral roots of anesthetized cats. We analyzed the cross-covariance (CCV) between the amplitudes of bilateral MSRs. Long-time series (5 to 8 h) of these bilateral MSRs exhibited transitory changes in their covariations (as measured by the zero-lag peak of their CCV), thus suggesting the existence of certain neural sources contributing to produce these changes. The aim of the present study was to show that spinal centers producing negative spontaneous cord dorsum potentials (nSCDPs) contribute to maintain correlations in the amplitude of bilateral MSRs. After spinal cord transection at the L1 segment, no significant changes were observed in the correlation between the amplitude of bilateral nSCDPs versus the amplitude of bilateral MSRs. However, this correlation, as well as the peak at zero lag in the CCV between bilateral MSRs and the CCV between bilateral nSCDPs, respectively, were abolished after a subsequent longitudinal bisection at the L1-S2 spinal segments. These results suggest that lumbar spinal neurons (bilaterally interconnected) contribute to maintain the synchronous fluctuations of bilateral MSRs.


Training Tomorrow's Doctors to Safeguard the Patients of Today: Using Medical Student Simulation Training to Explore Barriers to Recognition of Elder Abuse.
In recognition of the fact that elder abuse is a global problem that doctors underrecognize and underreport, a simulation training session for undergraduate medical students was developed. The primary objective of this qualitative study was to examine barriers to and drivers of medical students making a diagnosis of elder abuse in simulated practice, with the goal of refining teaching methods and informing future teaching sessions for other clinical teachers. Third-year medical students (Newcastle University, United Kingdom) undertook a simulation scenario with a high-fidelity mannequin representing an elder abuse victim. After the simulation scenario, students underwent a semistructured debriefing. A tripartite approach to data collection was employed that included audio recordings of the simulation, data sheets capturing students' thoughts during the scenario, and postscenario debriefing. A different researcher analyzed each data set in isolation before discussions were held to triangulate findings from the data sets. Forty-six students undertook the scenario; none declined to participate. A number of barriers to students diagnosing elder abuse were identified. Students held a low index of suspicion for elder abuse and were overly optimistic regarding the etiology of the individual's injuries. Students lacked the confidence to raise concerns about possible elder abuse, believing that certainty was required before doing so. There was widespread confusion about nomenclature. These findings provide clinical teachers with important topic areas to address in future teaching sessions. Simulation, as a method to teach about elder abuse in a reproducible and immersive fashion, is recommended to clinical teachers.


[Cost evaluation of ventilator-associated pneumonia in adult patients in a general hospital in Chile].
Ventilator-associated pneumonia (VAP) is an adverse event that increases morbidity, mortality and costs due to a prolonged stay and requirement of microbiological studies and antimicrobial therapy. There is not recent data of VAP costs in Chile. To evaluate additional costs in adult patients with VAP compared to controls in a general hospital in the Metropolitan Area. Use of the PAHO paired casecontrol protocol for cost evaluation associated to nosocomial infections and estimation of cost in excess per VAP event. Length of stay (LOS) in excess, antimicrobial consumption in daily-defined doses (DDD), and number of microbiological studies were compared between both groups. From 2012 to 2015, 18 patients with VAP events were identified with their respective controls. LOS exceeded 6.1 days on average among patients with VAP respect to controls (p < 0.05). DDD was higher among patients with VAP (difference 11.7 DDD) as well as number of cultures (3.2 higher on average, p < 0.05). Cost in excess per VAP event reached 4,475 USD. In our Centre, VAP events are associated to a higher LOS, antimicrobial consumption and microbiological studies.


Systematically analyzing rare variants of autosomal-dominant genes for sporadic Parkinson's disease in a Chinese cohort.
Studies have shown that rare variants of Mendelian genes for Parkinson's disease (PD) contribute to sporadic PD in the Caucasian population, which lacked confirmation in the Chinese population. Because the autosomal-dominant PD (AD-PD) had a phenotype closely resembling sporadic PD, we performed a systematic analysis of 7 AD-PD genes (SNCA, LRRK2, GIGYF2, VPS35, EIF4G1, DNAJC13, and CHCHD2) in 1456 Chinese sporadic PD patients and 1568 controls. Overall, 72 rare variants were identified, 7 of which were classified as likely pathogenic, 63 of which were categorized as of uncertain significance, and 2 of them were predicted to be likely benign. These AD-PD genes represented a clear enrichment of rare variants in PD patients from a burden analysis (p = 0.003), and significant differences could still be observed when likely pathogenic variants were removed (p = 0.027). The gene-based association testing also reached significance for LRRK2 (p = 0.004) and remained statistically significant after the Bonferroni correction. This report suggested that rare variants of AD-PD genes had a role in the Chinese sporadic PD cohort, especially for those rare variants of LRRK2.


Separation and Quantification of Some Alkaloids from Fumaria parviflora by Capillary Isotachophoresis1.
The isotachophoretic separation of some isoquinoline alkaloids in acid-base partially purified extracts from Bulgarian FUMARIA PARVIFLORA was studied. The electrolyte system for model mixtures of alkaloids (-)-stylopine, (-)-canadine, coptisine, berberine, protopine, cryptopine, chelidonine, bulbocapnine, papaverine, parfumine and for the plant extracts contained the leading ion K (+) (0.01 M), counter ion CH (3)COO (-), pH (L) 5.5, and the terminating ion H (+) (acetic acid 0.01 M). In the plant extracts, protopine and parfumine were quantitatively determined during F. PARVIFLORA growth and development in the term May-June 1984.


Factor from rat liver with antiinvasive potential on rat ascites hepatoma cells.
An acid/ethanol extract of normal rat liver, both in vitro and in vivo, inhibited the invasion by a highly invasive subpopulation of rat ascites hepatoma cells, AH 130 (LC-AH cells). The addition of 10-80 micrograms/ml extract inhibited the formation of penetrated colonies of LC-AH cells underneath the cultured mesothelial cell (M-cell) monolayer. The tumor cells pretreated with the extract showed the diminished colony formation. Preincubation of the extract with plasma membranes prepared from LC-AH cells abolished the effect of the extract, suggesting a binding of the inhibitory entity [tentatively termed as "invasion-inhibiting factor" (IIF)] to the tumor cell surface. The extract did not inhibit the growth of LC-AH cells, but suppressed their directed migration underneath the M-cell monolayer. A concomitant i.p. injection of the extract with LC-AH cells into rats prevented the invasion by tumor cells of the peritoneum and formation of tumor nodules in the peritoneum and mediastinum, indicating that IIF inhibited the tumor cell invasion and metastasis in vivo, as well. Upon ultrafiltration and gel fractionation, about 60% of IIF activity was recovered in the fraction corresponding to the molecular weight in the range of Mr 3000-4000. This activity was heat-stable at 100 degrees C at neutral pH but labile at acidic pH and was inactivated by the treatment with pronase. The rest of the activity of IIF was found in the fraction of more than Mr 25,000.


The subretinal fluid in retinal detachment. A cytologic study.
Following retinal detachment, subretinal fluid (SRF) fills the neoformed space. Subsequently subretinal and preretinal strands of proliferative tissue begin to form. We have collected the subretinal fluid withdrawn during retinal detachment surgery. We have studied subretinal fluid cytologically to evaluate the number and the type of cells present in the fluid, and by means of transmission electron microscopy. The first cell type to be present in the fluid represented degenerated aspects of pigmented epithelial cells (PECs). Successively, other cell types appeared in the fluid as nerve cells (rods, cones and glial cells), macrophages and well preserved pigmented epithelial cells.


[In vitro and in vivo effects of 5-aminolevulinic acid-mediated photodynamic therapy against oral squamous cell carcinoma].
Objective: To investigate the in vitro and in vivo effects of 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy against oral squamous cell carcinoma (OSCC) and preliminarily explore the possible mechanisms. Methods: SCC25 cells were divided into the control group (5-ALA of 0 mg/L) and the experimental group (5-ALA of 10, 25, 50, 100 and 150 mg/L). The production of protoporphyrin Ⅸ (PpⅨ) induced by 5-ALA in SCC25 cells was detected using the flow cytometry. SCC25 cells were divided into the control group (5-ALA of 0 mg/L), lazer alone group, 5-ALA alone group (5-ALA of 100 mg/L) and the 5-ALA combined with laser irradiation group (5-ALA of 5, 10, 25, 50 and 100 mg/L), the cytotoxicity of 5-ALA combined with laser irradiation (wave length 635 nm, power density 87 mW/cm(2) and laser dose 10.4 J/cm(2)) was evaluated in SCC25 cells using the methyl thiazolyltetrazolium assay (incubation times of 4, 8 and 12 h in each group) and the induction effect of combination treatment on the cell apoptosis was assessed by the flow cytometry (incubation time of 12 h in each group). The intracellular production of reactive oxygen species (ROS) triggered by 5-ALA combined with laser irradiation was determined using a fluorescence probe method (incubation time of 12 h in each group). A mouse OSCC xenograft model bearing SCC25 tumor was built, and the mice were divided into control group (saline), 5-ALA group (5-ALA of 50 mg/kg) and 5-ALA combined with laser irradiation group (5-ALA of 10, 25 and 50 mg/kg). Antitumor effect of 5-ALA combined with laser irradiation (wave length 635 nm, power density 158 mW/cm(2) and laser dose 94.8 J/cm(2)) was further measured. Results: 5-ALA induced the production of PpⅨ in SCC25 cells in a drug concentration (0-150 mg/L)-and incubation time (0-24 h)-dependent manner. When the 5-ALA concentration was 100 mg/L, the intracellular PpⅨ production was in a relatively stable state. Cell viability and apoptosis rate of 5, 10, 25, 50, 100 mg/L 5-ALA combined with laser irradiation are, respectively, (82.3±5.2)%, (3.13±0.38)%; (74.6±9.3)%, (5.38±0.55)%; (38.3±9.7)%, (17.97±2.72)%; (9.2±3.8)%, (24.47±3.37)%; (7.2±0.8)%, (43.01±5.96)%, which indicated that 5-ALA combined with laser irradiation notably inhibited the growth of SCC25 cells and also induced significant cell apoptosis compared with the control group [(96.3±6.0)%, (0.35±0.13)%, P<0.05]. After combination treatment (5-ALA of 5, 10, 25, 50 and 100 mg/L combined with laser irradiation, the mean fluorescence intensity of dichlorofluorescein is (1.46±0.12)×10(4), (2.16±0.30)×10(4), (3.57±0.34)×10(4), (81.70±13.05)×10(4), (113.00±7.35)×10(4), respectively, a large amount of ROS was produced in SCC25 cells compared with the control group [(0.96±0.15) ×10(4), P<0.05], which was in positive correlation with the intracellular PpⅨ content. 5-ALA (concentration of 10, 25 and 50 mg/kg) combined with laser irradiation greatly suppressed the tumor growth in SCC25 tumor-bearing mice compared to the control group (P<0.05). Conclusions: 5-ALA-mediated photodynamic therapy can trigger the generation of intracellular ROS that has significant cytotoxicity and apoptosis induction effect, and thus inhibit the tumor growth both in vitro and in vivo.


The incidence of basal cell carcinoma in Croatia: an epidemiological study.
The aim of the study was to investigate the basal cell carcinoma (BCC) incidence in Croatia in the 2003-2005 period. Data were collected from University Department of Dermatology and Venereology, Zagreb University Hospital Center and National Cancer Registry. The age-specific incidence rate and age-standardized incidence rate were calculated per 100,000 inhabitants according to the latest population census in Croatia from 2001. In the study period, there were 7,244 BCC cases (3,519 men and 3,725 women) in Croatia. The crude incidence rate for the Croatian population of 100,000 was 54.9 for men and 53.9 for women. The age-standardized incidence rate (adjusted for the world standard population) was 33.6 for men and 24.5 for women. The head and neck were almost exclusive localizations of BCC. The highest BCC incidence was recorded in Zadar County. The incidence of BCC was high in both littoral and inland counties of Croatia. Study results will serve as reference figures on studying the trend of BCC incidence in Croatia and Europe in the forthcoming years.


[Changes in lipid spectrum in rats with chronic heart failure of different severity on the background of angiotensin-converting enzyme inhibitors and beta-adrenoblockers].
The character of lipid spectrum changes in rats with experimental heart failure of non-ischemic genesis depended on its severity. In mild heart failure there was found an increase in the low density lipoprotein levels, whereas in the severe one--a decrease of total cholesterol levels at the expense of the low density lipoproteins. The ACE inhibitors produced no significant changes in the lipid spectrum. The effect of beta-adrenoblockers was determined by their selectivity for beta1-adrenoreceptors. The most selective drugs were distinguished by the metabolically neutral activity. On the contrary, nonselective beta-adrenoblockers increased the degree of plasma atherogeneity.


Pulmonary hypertension in patients with interstitial lung disease.
Interstitial lung diseases (ILDs) comprise a broad and heterogeneous group of more than two hundred diseases with common functional characteristics. Their diagnosis and management require a multidisciplinary approach. This multidisciplinary approach involves the assessment of comorbid conditions including pulmonary hypertension (PH) that exerts a dramatic impact on survival. The current World Health Organization (WHO) classification of PH encompasses many of the interstitial lung diseases into WHO Group 3, while sarcoidosis, Pulmonary Langerhans Cell Histiocytosis and lymphangioleiomyomatosis are placed into WHO Group 5 as diseases with unclear or multifactorial mechanisms. Connective tissue diseases could span any of the 5 WHO groups based on the primary phenotype into which they manifest. Interestingly, several challenging phenotypes present with features that overlap between two or more WHO PH groups. Currently, PH-specific treatment is recommended only for patients classified into WHO Group 1 PH. The lack of specific treatment for other groups, including PH in the setting of ILD, reflects the poor outcomes of these patients. Thus, identification of the optimal strategy for ILD patients with PH remains an amenable need. This review article provides a brief overview of biomarkers indicative of vascular remodeling in interstitial lung disease, summarizes the current state of knowledge regarding patients with PH and ILD and highlights future perspectives that remain to be addressed.


Outcome of repeated prostatic biopsy during active surveillance: implications for focal therapy.
Active surveillance (AS) is commonly recommended for men with localized low-intermediate-risk prostate cancer (PCa). The aim of our study was to assess the probability that patients with PCa would develop unfavorable disease features (UDF) while under AS for the purpose of evaluating whether immediate hemiablation therapy (HAT) could bring clinical benefit to selected patients. In our cohort of AS patients, 157 were diagnosed with unilateral PCa. Using five different definitions of UDF, patients' data were used to simulate the theoretical outcome whether these patients were managed by immediate unilateral HAT or remained on AS. The mean age at the time of diagnosis was 67 years (range 47-81). The median follow-up was 5.4 years [interquartile range (IQR) 3.4-8]. Baseline characteristics included a median PSA value of 5.5 ng/ml (IQR 4.5-7), median number of biopsy taken of 10 (IQR 6-10), and maximum cancer percentage on any core of 10 (IQR 5-20). Of the 157 patients, 144 (92 %) had a Gleason score (GS) of ≤6. Using the whole range of definition for UDF, 10-47 % of patients developed UDF while under AS. Using baseline GS, maximum percentage of cancer on any core, and PSA density, we found significant trends for higher development of UDF for patients under AS. The majority of our patients did not develop UDF while under AS. Our study, thus, suggests that careful patient selection for focal therapy should be performed to avoid subjecting patients to unnecessary treatment.


The myelinated axon is dependent on the myelinating cell for support and maintenance: molecules involved.
The myelin-forming cells, oligodendrocytes and Schwann cells, extend processes that spirally wrap axons and provide the insulation that allows rapid saltatory conduction. Recent data suggest a further role for the myelin-forming cells in axonal support and maintenance. This Mini-Review summarises some of the data that support this view and highlights the molecules involved.


Myocardial toxicity of cyclosporin A: inhibition of calcium ATPase and nitric oxide synthase activities and attenuation by fructose-1,6-diphosphate in vitro.
Use of cyclosporin A (CsA) in transplantation medicine has been shown to cause a number of toxic cellular side effects, which has prompted a search for formulations that afford protection from these undesirable sequelae. Previously we demonstrated that fructose-1,6-diphosphate (FDP) can reverse a variety of toxic cellular effects that arise upon use of various chemical agents. The present studies were undertaken to study the effects of CsA on rat myocardial Ca2+, calmodulin (Cam)-dependent enzymes such as Ca2+ ATPase and nitric oxide synthase (NOS) and the role of FDP in attenuating these changes in vitro. Rat ventricular sarcoplasmic Ca2+ ATPase was studied by measuring the inorganic phosphorous liberated on ATP hydrolysis and rat heart 100,000 g fraction NOS activity by monitoring the formation of [3H]-citrulline in the presence of 10-1000 microM CsA and 1000 microM CsA + 1000 microns FDP in vitro. CsA in all concentrations significantly (P < 0.001) inhibited both Ca2+ ATPase and NOS activities of rat myocardium and FDP at 1000 microM concentration completely reversed the 1000 microM CsA-inhibited Ca2+ ATPase and cNOS activities of rat myocardium. These data indicate that CsA may inhibit Ca2+ ATPase and NOS activities in the rat myocardium through interference with its Ca2+/Cam-mediated events and thus may cause myocardial toxicity. FDP may reverse these changes.


Paradox of using intensive lowering of blood glucose in diabetics and strategies to overcome it and decrease cardiovascular risks.
Hyperglycemia significantly increases the risk of cardiovascular disease (CVD) in diabetics. However, it has been shown by a series of large scale international studies that intensive lowering of blood glucose levels not only has very limited benefits against cardiovascular problems in patients, but may even be harmful to patients at a high risk for CVD and/or poor long-term control of blood glucose levels. Therefore, Western medicine is faced with a paradox. One way to solve this may be administration of Chinese herbal medicines that not only regulate blood glucose, blood fat levels and blood pressure, but also act on multiple targets. These medicines can eliminate cytotoxicity of high glucose through anti-inflammatory and anti-oxidant methods, regulation of cytokines and multiple signaling molecules, and maintenance of cell vitality and the cell cycle, etc. This allows hyperglycemic conditions to exist in a healthy manner, which is called "harmless hyperglycemia" Furthermore, these cardiovascular benefits go beyond lowering blood glucose levels. The mechanisms of action not only avoid cardiovascular injury caused by intensive lowering of blood glucose levels, but also decrease the cardiovascular dangers posed by hyperglycemia.


Incomplete bladder emptying in patients with stroke: is detrusor external sphincter dyssynergia a potential cause?
To delineate the frequency, clinical risk factors, and urodynamic mechanisms of incomplete bladder emptying (IBE) among patients with recent stroke. Retrospective study. Inpatient setting in the rehabilitation ward of a university hospital. All patients with acute stroke admitted for rehabilitation between January and December 2005, excluding those with a history of lower-urinary tract symptoms and urologic diseases. Eighty-two patients (42 women and 40 men; mean age, 65.5 y) were included. Not applicable. We measured postvoid residual (PVRs) by catheterization or by using an ultrasonic bladder scanner. Twenty-five patients (30.5%) had IBE with PVRs greater than 100 mL on 2 consecutive days. Patients with IBE were evaluated by a urologist and subsequently underwent urodynamic studies. The presence of IBE was significantly associated with urinary tract infection (P<.001) and aphasia (P=.046). The presence of IBE was not related to sex, stroke location, nature of stroke (hemorrhagic or ischemic), history of diabetes mellitus, or previous stroke. Urodynamic studies done on 22 patients with IBE revealed acontractile detrusor in 8 patients (36%) and detrusor underactivity in 3 (14%). Eleven patients (50%) had detrusor-external sphincter dyssynergia (DESD) combined with normative detrusor function (5 patients) or detrusor hyperactivity (6 patients); all but 1 of these patients had a supratentorial lesion. The presence of DESD was associated with a longer onset-to-evaluation interval (P=.018) [corrected] and spasticity of the stroke-affected lower limb (P=.02). [corrected] Diabetes mellitus was associated with the presence of acontractile detrusor or detrusor underactivity (P=.03). IBE is common among patients with stroke and is caused by decreased detrusor contractility or DESD. Spasticity of the external urethral sphincter is a possible pathophysiologic mechanism of DESD.


PRRT2 gene variant in a child with dysmorphic features, congenital microcephaly, and severe epileptic seizures: genotype-phenotype correlation?
Mutations in Proline-rich Transmembrane Protein 2 (PRRT2) have been primarily associated with individuals presenting with infantile epilepsy, including benign familial infantile epilepsy, benign infantile epilepsy, and benign myoclonus of early infancy, and/or with dyskinetic paroxysms such as paroxysmal kinesigenic dyskinesia, paroxysmal non-kinesigenic dyskinesia, and exercise-induced dyskinesia. However, the clinical manifestations of this disorder vary widely. PRRT2 encodes a protein expressed in the central nervous system that is mainly localized in the pre-synaptic neurons and is involved in the modulation of synaptic neurotransmitter release. The anomalous function of this gene has been proposed to cause dysregulation of neuronal excitability and cerebral disorders. We hereby report on a young child followed-up for three years who presents with a spectrum of clinical manifestations such as congenital microcephaly, dysmorphic features, severe intellectual disability, and drug-resistant epileptic encephalopathy in association with a synonymous variant in PRRT2 gene (c.501C > T; p.Thr167Ile) of unknown clinical significance variant (VUS) revealed by diagnostic exome sequencing. Several hypotheses have been advanced on the specific role that PRRT2 gene mutations play to cause the clinical features of affected patients. To our knowledge, the severe phenotype seen in this case has never been reported in association with any clinically actionable variant, as the missense substitution detected in PRRT2 gene. Intriguingly, the same mutation was reported in the healthy father: the action of modifying factors in the affected child may be hypothesized. The report of similar observations could extend the spectrum of clinical manifestations linked to this mutation.


Cell culture from sponges: pluripotency and immortality.
Sponges are a source of compounds with potential pharmaceutical applications. In this article, methods of sponge cell culture for production of these bioactive compounds are reviewed, and new approaches for overcoming the problem of metabolite supply are examined. The use of embryos is proposed as a new source of sponge material for cell culture. Stem cells are present in high amounts in embryos and are more versatile and resistant to infections than adult cells. Additionally, genetic engineering and cellular research on apoptotic mechanisms are promising new fields that might help to improve cell survival in sponge-cell lines. We propose that one topic for future research should be how to reduce apoptosis, which appears to be very high in sponge cell cultures.


Nonspecific perichondritis of the lumbar spine.
A teenage girl with soft tissue inflammation involving the L2-S1 region of the lumbar region is reported. Magnetic resonance (MR) imaging revealed high-signal lesions on T2-weighted images in association with contrast enhancement. Histology revealed nonspecific perichondritis with mononuclear inflammatory infiltration of the perichondrium and connective tissue. Six months after treatment, MR imaging was normal. No similar case of perichondritis with involvement of the lumbar region could be found in the current literature.