Effects of population structures and selection strategies on the purging of inbreeding depression due to deleterious mutations.
Stochastic simulations were run to compare the effects of nine breeding schemes, using full-sib mating, on the rate of purging of inbreeding depression due to mutations with equal deleterious effect on viability at unlinked loci in an outbred population. A number of full-sib mating lines were initiated from a large outbred population and maintained for 20 generations (if not extinct). Selection against deleterious mutations was allowed to occur within lines only, between lines or equal within and between lines, and surviving lines were either not crossed or crossed following every one or three generations of full-sib mating. The effectiveness of purging was indicated by the decreased number of lethal equivalents and the increased fitness of the purged population formed from crossing surviving lines after 20 generations under a given breeding scheme. The results show that the effectiveness of purging, the survival of the inbred lines and the inbreeding level attained are generally highest with between-line selection and lowest with within-line selection. Compared with no crossing, line crossing could lower the risk of extinction and the inbreeding coefficient of the purged population substantially with little loss of the effectiveness of purging. Compromising between the effectiveness of purging, and the risk of extinction and inbreeding coefficient, the breeding scheme with equal within- and between-line selection and crossing alternatively with full-sib mating is generally the most desirable scheme for purging deleterious mutations. Unless most deleterious mutations have relatively large effects on fitness in species with reproductive ability high enough to cope with the depressed fitness and thus increased risk of extinction with inbreeding, it is not justified to apply a breeding programme aimed at purging inbreeding depression by inbreeding and selection to a population of conservation concern.


Radon, smoking and lung cancer risk: results of a joint analysis of three European case-control studies among uranium miners.
A combined analysis of three case-control studies nested in three European uranium miner cohorts was performed to study the joint effects of radon exposure and smoking on lung cancer death risk. Occupational history and exposure data were available from the cohorts. Smoking information was reconstructed using self-administered questionnaires and occupational medical archives. Linear excess relative risk models adjusted for smoking were used to estimate the lung cancer risk associated with radon exposure. The study includes 1046 lung cancer cases and 2492 controls with detailed radon exposure data and smoking status. The ERR/WLM adjusted for smoking is equal to 0.008 (95% CI: 0.004-0.014). Time since exposure is shown to be a major modifier of the relationship between radon exposure and lung cancer risk. Fitting geometric mixture models yielded arguments in favor of a sub-multiplicative interaction between radon and smoking. This combined study is the largest case-control study to investigate the joint effects of radon and smoking on lung cancer risk among miners. The results confirm that the lung carcinogenic effect of radon persists even when smoking is adjusted for, with arguments in favor of a sub-multiplicative interaction between radon and smoking.


[Dyspareunia and Sjögren's syndrome].
Dyspareunia is frequently associated with a psychiatric origin, particularly in patients with no obvious vulvovaginal or pelvic disease. The aim of this study was to assess the frequency of dry syndrome in patients with dyspareunia and to evaluate the main clinical and biological features and follow-up data for women with dyspareunia and dry syndrome. Twenty-two patients presenting chronic idiopathic dyspareunia (without clear vulvovaginal dermatosis or infection) were included in this retrospective study. All patients underwent history-taking, gynecological examination, a Schirmer tear test, a sugar test, labial salivary gland biopsy assessment and immunological examination. A diagnosis of Sjögren's syndrome was considered where histological examination of the salivary glands showed a lymphocyte infiltration corresponding to stage 3 or 4 in the Chisholm classification. Diagnosis of dry syndrome without Sjögren's syndrome was made in patients with xerostomia and/or xerophthalmia without a specific histological picture of Sjögren's syndrome or immunological abnormalities at salivary gland biopsy. Based on our criteria, 10 patients (45%) had dry syndrome, including 4 with Sjögren's syndrome and 6 with dry syndrome without Sjögren's syndrome. 9 of these 10 patients presented either xerostomia (7 cases) and/or xerophthalmia (7 cases). Vaginal dryness was reported by 3 of the 10 women with dry syndrome but also by 4 of 12 women without dry syndrome. Examination of the vulva showed no particular clinical features and treatment with an emollient was not effective in all cases. This study showed a high frequency of dry syndrome in patients with chronic "idiopathic" dyspareunia. The incidence of the condition was even greater in women with functional conditions evocative of dry syndrome. Women presenting dyspareunia with no clearly related clinical causes should thus be carefully assessed for dry syndrome.


Maintaining the continuum of en route care.
As life-sustaining and life-preserving surgical capability is moved far forward, it creates the opportunity to salvage casualties who may have otherwise died of their wounds. The remarkable capabilities and effectiveness of the small, austere surgical resuscitation teams (mobile forward surgical team, flying ambulance surgical trauma, forward resuscitative surgery system teams) has been amply demonstrated during the recent conflicts of Operation Iraqi Freedom and Operation Enduring Freedom. The life-saving capability of far-forward surgery creates the need for a new and unique capability, which is the cornerstone of the en route care continuum, namely, the ability to move stabilized, but not necessarily stable, patients. The current system of en route care serves as a primary and indispensable portion of the continuum of critical care. The scope of this article describes the origins, composition, equipment sets, medical considerations, and future directions of the en route care support process and the U.S. Air Force Critical Care Aeromedical Transport Teams.


[Multicystic renal dysplasia. Spontaneous remission of a hypertrophic form].
A case of spontaneous regression of the tumor type of multicystic dysplastic kidney (MDK) is reported. This case is consistent with recent data on the natural history of MDK. The classical therapeutic approach which involves surgery is discussed in the context of this case and of others with a similar course.


The effectiveness of mass communication to change public behavior.
This article provides an overview of the ways in which mass communication has been used -- or can be used -- to promote beneficial changes in behavior among members of populations. We use an ecological perspective to examine the ways in which mass media interventions can be used to influence public behavior both directly and indirectly. Mass media interventions that seek to influence people directly -- by directly targeting the people burdened by the public health problem of concern and/or the people who influence them -- have a long basis in public health history, and recent reviews have clarified our expectations about what can be expected from such approaches. Mass media interventions that seek to influence people indirectly -- by creating beneficial changes in the places (or environments) in which people live and work -- have equal if not greater potential to promote beneficial changes in population health behaviors, but these are currently less explored options. To have the greatest possible beneficial influence on public behavior with the public health resources available, we recommend that public health program planners assess their opportunities to use media to target both people and places in a manner that complements and extends other investments being made in population health enhancement.


Phase II trial of preoperative chemotherapy for breast cancer: Japan Breast Cancer Research Network (JBCRN)-02 trial.
Neoadjuvant chemotherapy (NAC) is one of the main strategies for patients with locally advanced breast cancer. In our previous study, biological markers such as estrogen receptor (ER), progesterone receptor (PgR), and HER2 were essential predictors of the effectiveness of NAC to help individualize treatment. This study examined the effect of NAC on the disease-free survival (DFS) of breast cancer patients. Furthermore, the study was expanded by adding Ki-67 as a biological marker, and examined the correlation between Ki-67 and the prognosis. Between September 2005 and September 2007, 43 patients with breast cancer received NAC and surgery. Four cycles of DC (doxorubicin: 60 mg/m(2) and cyclophosphamide: 500 mg/m(2)) were administered intravenously (i.v.) on day 1 every 21 days, followed by 12 cycles of paclitaxel i.v. (80 mg/m(2)) every 7 days, prior to surgery. The primary endpoint was the pathological complete response (pCR) rate and the secondary endpoint was DFS; the pCR rate was estimated for each groups stratified by the presence or absence of different factors (PcR, ER/PgR, and Ki-67). The clinical response (cCR+cPR) rate was 81.0%, and the pCR rate was 25.6%. The pCR rate was 75, 50, 9 and 0% in HER2(+)/ER(-), HER2(+)/ER(+), HER2(-)/ER(-), and HER2(-)/ER(+) patients, respectively. The 4-year DFS rate was estimated at 78% for all patients. The HER2 status was an independent predictor of pathological complete response (pCR). The DFS rate of patients with lower Ki-67 values (<15%) was higher than that of patients with higher Ki-67 values (≥15%). The treatment-related adverse events were manageable: the majority were mild, but five patients experienced grade 3 (neutropenia and sensory neuropathy) adverse events. DC followed by weekly paclitaxel is an active and manageable preoperative regimen for breast cancer patients. HER2 overexpression may be a good predictive marker of pCR, and the Ki-67 value after NAC may be a prognostic factor for DFS.


Comparative ultrastructure of juvenile and adult nuchal organs of an annelid (Polychaeta: Opheliidae).
Opheliid nuchal organs are composed of ciliated cells, retractor muscles, and sensory cells. The perikarya of sensory cells are located in the posterior portion of the brain, and their distal processes extend along the body wall, as the nuchal nerve, and terminate just anterior to the ciliated region. The nuchal nerve of the juvenile is composed of 30-35 dendrites; the adult nuchal nerve has 35-40 dendrites. The ends of the sensory dendrites form sensory bulbs which are clustered around the olfactory chamber, and each bulb bears a modified cilium. Sensory cilia lose their axonemes and extend as microvillous-like structures into the olfactory chamber. Supportive cells delineate approximately the posterior and dorsal portions of the chamber with sensory bulbs forming the remaining ventral and anterior portions. On the lateral aspect of the chamber, cuticular matrix. The adult nuchal organ is larger than that of the juvenile, and the sensory portion of the olfactory chamber wall is expanded. Expansion of the sensory area is apparently the result of size increase in sensory bulbs and by intrusion of supportive cells between sensory bulbs.


Treatment of tardive dyskinesia with vitamin E.
Vitamin E (alpha-tocopherol), a free-radical scavenger, has been reported to improve symptoms of tardive dyskinesia. The authors attempted to replicate this finding under more controlled conditions in a larger study group. Fifteen inpatients and six outpatients with tardive dyskinesia received up to 1600 IU/day of vitamin E for 6 weeks in a double-blind, placebo-controlled crossover study. Abnormal Involuntary Movement Scale (AIMS) examinations of these patients were videotaped and rated independently by two trained raters. Levels of neuroleptic medication and vitamin E were measured during both treatment periods. Eighteen patients who demonstrated high blood levels of vitamin E were included in the data analysis. Vitamin E levels were significantly higher while the patients were receiving vitamin E than while they were receiving placebo. For all 18 patients, there were no significant differences between AIMS scores after receiving vitamin E and AIMS scores after receiving placebo. In agreement with previous studies, however, the nine patients who had had tardive dyskinesia for 5 years or less had significantly lower AIMS scores after receiving vitamin E than after receiving placebo. There were no changes in neuroleptic levels during vitamin E treatment. Vitamin E had a minor beneficial effect on tardive dyskinesia ratings in a selected group of patients who had had tardive dyskinesia for 5 years or less. This effect was not due to an increase in blood levels of neuroleptic medications.


[Plasmid-mediated cephalosporinase among extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae].
To investigate the prevalence and genotype of plasmid-mediated cephalosporinase (AmpC) beta-lactamase in extended-spectrum-beta-lactamase-producing (ESBL) Escherichia coli and Klebsiella pneumoniae. 24 strains of cefoxitin-resistant ESBL-producing E. coli and 8 strains of K. pneumoniae were collected from January to December 2001 at Beijing Chaoyang Hospital. Analytical isoelectric focusing electrophoresis was used to measure the pI of the beta-lactamase. Conjugation experiment was used to study the transfer of cefoxitin resistance. The homology of the isolates was determined by pulsed field gel electrophoresis (PFGE). Plasmid-mediated AmpC enzyme genes were amplified and sequenced by using multiplex PCR. The prevalence of ESBL-producing E. coli and K. pneumoniae were 16.8% (49/292) and 16.5% (35/212), respectively. The prevalence of AmpC enzyme among ESBL-producing E. coli and K. pneumoniae isolates were 2.0% (1/49) and 17.1% (6/35), respectively. These 7 isolates produced DHA-1 AmpC enzyme. One strain of K. pneumoniae could transfer cefoxitin resistance to the recipient. Among 7strains, 5 strains produced CTX-M-3 and 2 produced SHV-12 ESBL. These 7 strains also produced TEM-1 broad-spectrum enzymes. These strains harbored 2 - 5 plasmids and one of them were 33 - 36 kb. PFGE showed these strains came from a variety of clones. In this hospital, 7 strains of the ESBL-positive E. coli and K. pneumoniae produced both DHA-1AmpC enzyme and CTX-M-3/SHV-12 ESBL. These 7 strains were from different clones.


How to Diagnose and Treat Breast Implant-Associated Anaplastic Large Cell Lymphoma.
After reading this article, the participant should be able to: 1. Describe the diagnostic criteria for breast implant-associated (BIA) anaplastic large cell lymphoma (ALCL). 2. Appropriately evaluate a patient with suspected BIA-ALCL, including appropriate imaging, laboratory tests, and pathologic evaluation. 3. Understand the operative treatment of BIA-ALCL, and indications for systemic chemotherapy and/or radiation therapy in advanced disease. 4. Understand treatment outcomes and prognosis based on stage of disease. The goal of this continuing medical education module is to present the assessment of a patient with suspected breast implant-associated anaplastic large cell lymphoma, the evaluation and diagnosis, the preoperative oncologic workup, the formation and execution of a surgical treatment plan, and the inclusion of adjunct treatments when indicated. In addition, staging and disease progression for treatment of breast implant-associated anaplastic large cell lymphoma are discussed.


Effects of phenobarbitone on the distribution, metabolism and biliary excretion of erythromycin in rats.
The administration of phenobarbitone to the rat (8 mg/100 g BW) once daily for 3 days significantly decreased the serum and tissue levels of erythromycin administered intraperitoneally (5 mg/100 g BW). Furthermore, phenobarbitone stimulated the hepatic microsomal N-demethylation of erythromycin and increased the biliary concentration and the biliary excretion rate of the unmetabolized antibiotic. These effects were accompanied by augmented liver mass and bile flow. The possibility is discussed that erythromycin concentrates in the bile through a specialized hepatic drug transport system, activated by phenobarbitone.


Degradation of xenobiotics by white rot fungi.
White rot fungi such as P. chrysosporium degrade the nonrepeating, nonstereoselective, insoluble polymer lignin under conditions of nutrient limitation. The attack on lignin principally involves extracellular peroxidases (ligninases) and hydrogen peroxide. Hydroxyl radicals may also make a significant contribution. The ligninolytic system lends itself to the degradation of xenobiotics, since these often have limited solubility in water and are not readily available in soil to intracellular metabolism. A nonspecific attack should proceed at a rate independent of the target's concentration and the fungal system would be expected to remediate soil contaminated with a mixture of compounds. This contrasts with the need for induction and problems with simultaneous metabolism encountered with bacterial inoculation. The P. chrysosporium system has been found active against such diverse substrates as DDT, lindane, PCBs, TNT and crystal violet, with substantial mineralization in many cases. Some like biphenyl and triphenylmethane dyes are structurally related to lignin substructures while others bear groups such as nitro (TNT) or halogen (PCP) that are absent from the natural polymer. The fate of transformed targets varies: pentachlorophenol is incorporated into soil organic matter as a result of fungal ligninase action, whereas highly lipophilic Aroclor PCBs are converted to water-soluble metabolites. Normally less toxic intermediates are generated: for example, with benzo[a]pyrene, mutagenic arene oxides do not appear in the white rot fungal system. In certain cases, purified ligninases were also active in degrading pollutants such as PCP, benzo[a]pyrene or triphenylmethane dyes. Methods of optimizing ligninase activity in fungal reactors have been described, such as the addition of surfactants and veratryl alcohol to the medium. It remains to be seen how molecular biology can provide further advances in maximizing the bioremediating activity of white rot fungi applied to contaminated soil.


Xenotransplantation--is it just around the corner?
Xenotransplantation will certainly solve the problem of the allogeneic organ shortage if long-term organ function can be achieved. Acceptance or rejection of the grafts depend not only on immunological mechanism but, as already recognized in chronic rejection (i.e. transplant atherosclerosis), on many other biochemical, physiological, and even morphological characteristics including inflammatory events originating from infections. The way in which signals in the form of hormones, neurotransmitters, enzymes and growth factors are translated in xenogeneic systems has not received adequate attention, if any at all. Central questions still to be answered are, how many xenogeneic hormonal and enzymatical interactions are possible? Are they able to maintain the metabolism in a foreign organ or body and for how long? In addition, transport molecules, the most important of which is albumin, must be considered when trying to achieve long-term survival using organs from a widely divergent species. Large quantities of foreign proteins, mediators and enzymes are released into the circulation when, for example, xenogeneic livers or other organs suffer from hyperacute rejection. The function of the liberated enzymes, hormones and inhibitors is far from being understood or even investigated. The amount of potassium released from a deteriorating xenogeneic liver is able to mimic a sometimes lethal cardioplegic solution. The first data coming from intravital microscopy herald that adhesion molecules, the newest but not last in the line of troubleshooters, interact with interleukins and eicosanoids and play a major role in the regulation of microcirculation.(ABSTRACT TRUNCATED AT 250 WORDS)


Paracoccidioides brasiliensis. A mycologic and immunochemical study of two strains.
The authors conducted a mycologic, immunochemical and molecular biology study on two strains of Paracoccidioides brasiliensis, one of them, called IBIA, isolated from soil in the municipality of IBIA (Minas Gerais) by Silva-Vergara et al. (1996, 1998), and the other, BAT, cultivated from a human case of paracoccidioidomycosis in Ribeirão Preto (São Paulo/Brazil) by Freitas Da Silva (1996). Both strains showed cotton-like (M) and yeast-like (Y) forms and were pathogenic for testicularly inoculated guinea pigs, producing granulomatous and/or suppurative orchitis. Immunochemically was demonstrated the presence of gp43 by double immunodiffusion, immunoelectrophoresis and immunoblotting.


Metoclopramide exaggerates stress-induced tachycardia in pregnant sheep.
Metoclopramide is often administered to hasten gastric emptying prior to cesarean section and during labor, but has also been demonstrated to increase catecholamine release during stress and to increase heart rate and blood pressure in nonpregnant humans. The purpose of this study was to examine the maternal and fetal effects of metoclopramide during maternal stress in pregnant ewes. After baseline measures, eight ewes were randomly allocated to receive either intravenous metoclopramide, 10 mg, or saline, followed in 10 min by nonpainful stress to increase mean arterial pressure 40%-45% for 30 s. At least 2 days later, the ewes received the alternate treatment. Metoclopramide, but not saline, increased resting maternal heart rate. In the 10 min after maternal stress, maternal heart rate was increased more after metoclopramide than after saline treatment, whereas maternal blood pressure, uterine blood flow, and fetal hemodynamic variables and arterial blood gas tensions did not differ between the two treatments. Whereas these results are not consistent with a generalized increase in sympathetic nervous system tone after a single dose of metoclopramide, they do suggest that metoclopramide may exaggerate tachycardia after stress, encountered frequently both during and after cesarean section.


The association of body mass index with complications and functional outcomes after surgery for closed ankle fractures.
This study assessed the association of classes of body mass index in kg/m2 (classified as normal weight 18.5 kg/m2 to 24.9 kg/m2, overweight 25.0 kg/m2 to 29.9 kg/m2, and obese ≥ 30.0 kg/m2) with short-term complications and functional outcomes three to six years post-operatively for closed ankle fractures. We performed a historical cohort study with chart review of 1011 patients who were treated for ankle fractures by open reduction and internal fixation in two hospitals, with a follow-up postal survey of 959 of the patients using three functional outcome scores. Obese patients had more severe overall complications and higher odds of any complication than the normal weight group, with adjusted odds ratio 1.67 (95% confidence interval (CI) 1.08 to 2.59; p = 0.021) and 1.71 (95% CI 1.10 to 2.65; p = 0.016), respectively. In total 479 patients (54.6%) responded to the questionnaire. Obese patients had worse scores on the Olerud and Molander Ankle Score (p < 0.001), Self-Reported Foot and Ankle Questionnaire (p = 0.003) and Lower Extremity Functional Scale (p = 0.01) than those with normal weight. In contrast, overweight patients did not have worse functional scores than those with normal weight. Obese patients had more complications, more severe complications, and worse functional outcomes three to six years after ankle surgery compared with those with normal weight. Cite this article: Bone Joint J 2017;99-B:1389-98.


Paraoxonase (PON1) polymorphisms in farmers attributing ill health to sheep dip.
Human serum paraoxonase (PON1) hydrolyses diazinonoxon, the active metabolite of diazinon, which is an organophosphate used in sheep dip. In a case-referent study, 175 farmers with ill health that they attributed to sheep dip nominated 234 referent farmers who also dipped sheep and whom they believed to be in good health. We calculated odds ratios for polymorphisms in PON1 at positions 192 and 55, and for PON1 activity with diazinonoxon as substrate. Cases were more likely than referents to have at least one R allele at position 192 (glutamine to arginine aminoacid substitution; odds ratio 1.93, 95% CI 1.24-3.01), both alleles of type LL (1.70, 1.07-2.68) at position 55, and to have diazoxonase activity below normal median (1.77, 1.18-2.67). Our results support the hypothesis that organophosphates contribute to the reported ill health of people who dip sheep.


Midcingulate involvement in progressive supranuclear palsy and tau positive frontotemporal dementia.
Progressive supranuclear palsy (PSP) patients often exhibit cognitive decline and behavioural changes during the disease course. In a subset, these symptoms may be the presenting manifestation and can be similar to those in frontotemporal dementia (FTD). However, correlation studies between quantitative imaging measures and detailed neuropsychological assessment are scarce. The aim of this study was to investigate the functional role of affected brain regions in cognition in PSP compared with controls and subsequently examine these regions in FTD patients with known tau pathology (FTD tau). 21 PSP patients, 27 healthy controls and 11 FTD tau patients were enrolled. All participants underwent neuropsychological testing and technetium-99m-hexamethyl-propylenamine-oxime single photon emission CT. Regression slope analyses were performed in statistical parametric mapping to find significant associations between neuropsychological test results and brain perfusion. PSP patients showed hypoperfusion in the midcingulate cortex (MCC) of which the posterior part correlated with Stroop III and Weigl. In FTD tau patients, MCC involvement was located more anterior and correlated with Stroop III and Wisconsin Card Sorting Test concepts. The degree of hypoperfusion in the anterior cortex and MCC in the disorders differed in the subgenual anterior cingulate cortex only. The posterior part of the MCC is prominently involved in the neurodegenerative process of PSP, and the severity of its hypoperfusion correlated with the extent of executive dysfunction. In FTD tau, this cognitive domain was associated with anterior MCC involvement. The degree of hypoperfusion in these regions did not differ between PSP and FTD tau. These observations provide insight into the role of the cingulate cortex in cognitive dysfunction in these neurodegenerative disorders and warrant further investigations.


Ontogeny of the phagocytic and bactericidal activities of turkey heterophils and their potentiation by Salmonella enteritidis-immune lymphokines.
Heterophils, the functional equivalent to the mammalian neutrophil, are important mediators of natural resistance against invasive pathogens in poultry. Young poultry are susceptible to pathogens, such as Salmonella enteritidis, during the first week post-hatch. No studies have evaluated the ontogeny of heterophil function in turkeys during the first few weeks post-hatch. Previous studies from our laboratory have shown day-old poults were protected against S. enteritidis organ invasion following immunoprophylactic administration of chicken S. enteritidis immune lymphokines. Therefore, the objective in the present study was to characterize the development of phagocytosis and bacterial killing by turkey heterophils during the first 3 weeks of life and to compare the effect of immune lymphokines on the development of heterophil phagocytosis and killing during the first 3 weeks post-hatch. Both functional phagocytosis and killing activities were age-dependent events. During the first 1-7 days post-hatch, little functional activity was demonstrated which apparently is associated with susceptibility. Optimal heterophil phagocytosis and killing activities were reached 14-21 days post-hatch. Administration immune lymphokines significantly potentiated phagocytosis (P < 0.01) and killing (P < 0.001) by turkey heterophils. In fact, immune lymphokine administration to 1-7-day-old poults augmented phagocytosis and killing activities of heterophils equivalent to levels found in functionally mature 14-21-day-old poults. These results demonstrate the ontogeny of the functional activity of the turkey heterophil is an age-related phenomenon, with inefficient phagocytosis and killing during the first week post-hatch. Prophylactic administration of immune lymphokines significantly potentiated the functional activity of the heterophil poults during the first 3 weeks of life. Most importantly the administration of immune lymphokines enhanced the functional activity of heterophils from 1-7-day-old poults to levels comparable to that of an immunologically mature bird.


How to avoid the interspecialty turf battle trap.
As competition and increased numbers of physicians heat up efforts to obtain hospital privileges, medical staffs and hospitals need to develop a quality-based privileging system that minimizes discord and protects from antitrust liability.


Ethics and the allocation of health resources to the elderly.
This paper examines some of the ethical issues confronting the allocation of scarce health resources in the context of an ageing society with increasing levels of chronic disease. The allocation of resources at both the micro and macro level is explored, utilising the ethical principles of patient-centred beneficence, autonomy, full beneficence and justice. The implications of the dominance of science and technology within health care are analysed along with the paternalistic and individualistic nature of traditional medical ethics. The possible variations in value systems between patients and health professionals are examined and a greater emphasis on patient autonomy is advocated. Such a change, it is argued, may well result in an actual decrease in demand for expensive high technology treatment.


Tracking Trends In Provider Reimbursements And Patient Obligations.
Primary payments--those made by insurance carriers--to office-based physicians rose moderately between 2013 and 2014. Payments declined for orthopedics and surgery while increasing for primary care and obstetrics-gynecology. Patients' payment obligations rose for all specialties, and deductibles were the largest category of increased patient spending.


An Evaluation of Bite Pattern in Children with Severe-Early Childhood Caries Before and After Complete Dental Rehabilitation.
The purpose of this study was to examine the changes in bite characteristics of children before and after the placement of multiple stainless steel crowns (SSCs) under general anesthesia (GA). Twenty children scheduled for treatment under general anesthesia who needed SSCs in three or more posterior quadrants were included in this study. The bite was digitally analyzed and recorded preoperatively and at one and four weeks postoperatively. The occlusion time, number of force outliers, and distribution of force at each visit was recorded and compared. The placement of the SSCs in children significantly improved the bite characteristics of the participants. The placement of the SSC did not alter occlusion time, and there were no significant differences in occlusion time. While there was an increase in the number of outliers in the first week after the placement of the crown, there was a reduction in the total number of outliers at the end of one month. All the patients treated with bilateral placement of an SSC showed a posterior balanced occlusion post-operatively, a finding that was retained over the one-month follow-up period. Bilateral placement of SSCs under general anesthesia does not significantly alter the occlusion of the child.


Brief screening for psychosis-like experiences.
Psychotic-like experiences (PLEs) are common, and are markers of poor mental health. This study examined the internal structure of a screening test, the Community Assessment of Psychic Experiences-Positive scale (CAPE-P) in a young Australian sample. A cross-sectional online survey, which included the CAPE-P, was completed by 1610 university students aged between 18 and 25 years. Confirmatory factor analyses compared 1-, 4-, and 5-factor models, and examined effects of omitting selected items. A 3-factor model, omitting items on magical thinking, grandiosity, paranormal beliefs and a cross-loading item produced the best fit. The resultant 15-item CAPE (CAPE-P15) had three subscales - Persecutory Ideation, Perceptual Abnormalities and Bizarre Experiences, all with high levels of internal consistency. The CAPE-P15 shows promise as a measure of positive, psychosis-like experiences, but further validation of this measure is required in community samples.


[Effect of beta-endorphin and myelopeptides on the cAMP level and proliferation of lymphocytes in vitro].
Beta-endorphin (10(-11)-10(-9) M) has been shown to induce naloxone-independent depression of the proliferative activity of human peripheral lymphocytes (HL), stimulated by pokeweed mitogen without affecting PHA-stimulated HL proliferation. Beta-endorphin (10(-10)-10(-7) M) also caused changes in HL cAMP level, that were blocked by naloxone. Marked individual sensitivity to beta-endorphin effects has been noted. It has been also shown that a bone marrow preparation, stimulating antibody production (myelopeptides), causes naloxone-independent depression in the proliferative activity of HL, stimulated by PHA and pokeweed mitogen, as well as naloxone-blocked decrease in cAMP HL level. It has been concluded that beta-endorphin interacts with several types of opiate lymphocyte receptors and that opioids, contained in myelopeptides, are involved in the realization of myelopeptide effect on lymphocytes.


Molecular recognition based iron removal from human plasma with imprinted membranes.
The aim of this study is to prepare ion-imprinted poly(2-hydroxyethyl methacrylate) (HEMA) based membranes which can be used for the selective removal of Fe3+ ions from Fe3+-overdosed human plasma. N-methacryloyl-(L)-glutamic acid (MAGA) was chosen as the ion-complexing monomer. In the first step, Fe3+ was complexed with MAGA and then, the Fe3+-imprinted poly(HEMA-MAGA) membranes were prepared by UV-initiated photo-polymerization of HEMA and MAGA-Fe3+ complex in the presence of an initiator (benzoyl peroxide). After that, the template (i.e., Fe3+ ions) was removed by using 0.1 M EDTA solution at room temperature. The specific surface area of the Fe3+-imprinted poly(HEMA-MAGA) membranes was found to be 49.2 m2/g and the swelling ratio was 92%. According to the elemental analysis results, the polymeric membranes contained 145.7 micromol MAGA/g polymer. The maximum adsorption capacity was 164.2 micromol Fe3+/g membrane. The relative selectivity coefficients of ion-imprinted membranes for Fe3+/Zn2+ and Fe3+/Cr3+ were 12.6 and 62.5 times greater than the non-imprinted matrix, respectively. The Fe3+-imprinted poly(HEMA-MAGA) membranes could be used many times without decreasing their Fe3+ adsorption capacities significantly.


The ABCB6 mutation p.Arg192Trp is a recessive mutation causing the Lan- blood type.
The membrane transporter ABCB6 has recently been shown to carry the high-frequency red-blood-cell (RBC) antigen Lan. All the Lan- individuals genotyped so far have inherited two recessive null mutations in ABCB6. The finding of a family with the Lan- blood type occurring in two successive generations prompted this study. Mutations in ABCB6 were searched by Sanger sequencing of exons and flanking intronic regions. Expression analysis of the Lan antigen was carried out by serology and flow cytometry. PCR-RFLP genotyping and Western blot analysis were also applied. All the Lan- members of this family were homozygous for c.574C>T, p.Arg192Trp in ABCB6 while the Lan+ members were heterozygous for this missense mutation encoded by the SNP rs149202834. Homozygosity for p.Arg192Trp was associated not only with absence of the Lan antigen, but also of the ABCB6 transporter in RBC membrane. The complete absence of Lan expression resulting from p.Arg192Trp homozygosity was confirmed by the subsequent identification of five unrelated Lan- individuals who were homozygous for this mutation and who developed an anti-Lan. We also provide evidence that three other single amino acid mutations in ABCB6 (c.826C >T, p.Arg276Trp; c.85_87delTTC, p.Phe29del; c.1762G >A, p.Gly588Ser) may also define ABCB6 null alleles. p.Arg192Trp is the first ABCB6 missense mutation causing the Lan- blood type and appears to be a relatively frequent cause of this rare blood type. Like the previously reported frameshift, nonsense and essential splice-site mutations in ABCB6, this missense mutation is recessive and defines an ABCB6 null allele. Other single amino acid mutations in ABCB6 may also cause the Lan- blood type.


Is homophobia associated with homosexual arousal?
The authors investigated the role of homosexual arousal in exclusively heterosexual men who admitted negative affect toward homosexual individuals. Participants consisted of a group of homophobic men (n = 35) and a group of nonhomophobic men (n = 29); they were assigned to groups on the basis of their scores on the Index of Homophobia (W. W. Hudson & W. A. Ricketts, 1980). The men were exposed to sexually explicit erotic stimuli consisting of heterosexual, male homosexual, and lesbian videotapes, and changes in penile circumference were monitored. They also completed an Aggression Questionnaire (A. H. Buss & M. Perry, 1992). Both groups exhibited increases in penile circumference to the heterosexual and female homosexual videos. Only the homophobic men showed an increase in penile erection to male homosexual stimuli. The groups did not differ in aggression. Homophobia is apparently associated with homosexual arousal that the homophobic individual is either unaware of or denies.


Development of the releasable asbestos field sampler.
The releasable asbestos field sampler (RAFS) was developed as an alternative to activity-based sampling (ABS; personal breathing zone sampling during a simulated activity). The RAFS utilizes a raking motion to provide the energy that releases particulate material from the soil and aerosolizes the asbestos fibers. A gentle airflow laterally transports the generated aerosol inside of a tunnel to one end where filter sampling cassettes or real-time instruments are used to measure asbestos and particulate release. The RAFS was tested in a series of laboratory experiments to validate its performance and then was deployed for field trials in asbestos-contaminated soil at multiple geographical locations. Laboratory data showed the RAFS generated repeatable and representative aerosol particulate concentrations. Field tests showed the RAFS aerosolized asbestos concentrations were statistically correlated with total particle concentrations. Field tests also showed the RAFS aerosolized asbestos concentrations were statistically correlated with asbestos concentrations measured by multiple ABS tests with different activities, different soil/environmental conditions, and at different geographical locations. RAFS provides a direct measurement of asbestos emission from soil in situ without consideration of meteorology and personal activity on the asbestos transport to the breathing zone.


Ring intermittency near the boundary of the synchronous time scales of chaotic oscillators.
In this Brief Report we study both experimentally and numerically the intermittent behavior taking place near the boundary of the synchronous time scales of chaotic oscillators being in the regime of time scale synchronization. We have shown that the observed type of the intermittent behavior should be classified as the ring intermittency.


Efficient inhibition of colorectal peritoneal carcinomatosis by drug loaded micelles in thermosensitive hydrogel composites.
In this work, we aim to develop a dual drug delivery system (DDDS) of self-assembled micelles in thermosensitive hydrogel composite to deliver hydrophilic and hydrophobic drugs simultaneously for colorectal peritoneal carcinomatosis (CRPC) therapy. In our previous studies, we found that poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCEC) copolymers with different molecular weight and PEG/PCL ratio could be administered to form micelles or thermosensitive hydrogels, respectively. Therefore, the DDDS was constructed from paclitaxel (PTX) encapsulated PCEC micelles (PTX-micelles) and a fluorouracil (Fu) loaded thermosensitive PCEC hydrogel (Fu-hydrogel). PTX-micelles were prepared by self-assembly of biodegradable PCEC copolymer (M(n) = 3700) and PTX without using any surfactants or excipients. Meanwhile, biodegradable and injectable thermosensitive Fu-hydrogel (M(n) = 3000) with a lower sol-gel transition temperature at around physiological temperature was also prepared. The obtained PTX-micelles in thermosensitive Fu-hydrogel (PTX-micelles-Fu-hydrogel) composite is a free-flowing sol at ambient temperature and rapidly turned into a non-flowing gel at physiological temperature. In addition, the results of cytotoxicity, hemolytic study, and acute toxicity evaluation suggested that the PTX-micelles-Fu-hydrogel was non-toxic and biocompatible. In vitro release behaviors of PTX-micelles-Fu-hydrogel indicated that both PTX and Fu have a sustained release behavior. Furthermore, intraperitoneal application of PTX-micelles-Fu-hydrogel effectively inhibited growth and metastasis of CT26 peritoneal carcinomatosis in vivo (p < 0.001), and induced a stronger antitumor effect than that of Taxol® plus Fu (p < 0.001). The pharmacokinetic study indicated that PTX-micelles-Fu-hydrogel significantly increased PTX and Fu concentration and residence time in peritoneal fluids compared with Taxol® plus Fu group. Thus, the results suggested the micelles-hydrogel DDDS may have great potential clinical applications.


Dyspnea Post Pulmonary Embolism from VD/VT and Stroke Volume Defects During Exercise.
Many pulmonary embolism (PE) patients report dyspnea on exertion after long-term treatment. Increased physiological dead space proportion (VD/VT) and decreased cardiac stroke volume reserve may distinguish persistent effects of PE itself from symptoms reflecting comorbid conditions or deconditioning. We retrospectively analyzed a consecutive series of incremental symptom-limited cardiopulmonary exercise tests that had been ordered to evaluate persistent dyspnea on exertion after long-term treatment for acute PE. Physiological VD/VT was determined at anaerobic threshold from exhaled CO2 and transcutaneous pCO2 (validated against paCO2 measurements). Cardiac stroke volume reserve was estimated at rest and at anaerobic threshold by VO2/pulse and previously validated estimates of Ca-vO2. Cardiopulmonary exercise tests were performed on 40 patients with post-PE dyspnea. In 65.0% (95% CI: 50.2%, 79.8%), VD/VT at anaerobic threshold was abnormally elevated, stroke volume reserve was decreased or both defects occurred. VD/VT at anaerobic threshold was abnormally elevated (≥ 0.27) in 35.0% (95% CI: 20.2%, 49.8%). VD/VT at anaerobic threshold significantly correlated with the extent of unmatched perfusion defects on subsequent VQ scans (p = 0.0085). In 55.0% (95% CI: 39.6%, 70.4%), stroke volume reserve at anaerobic threshold was abnormally decreased (≤ 128% of the resting value). Both defects were present in 25.0% (95% CI: 11.6%, 38.4%). Increased VD/VT at anaerobic threshold and decreased stroke volume reserve during exercise are common among patients with dyspnea on exertion after long-term treatment of PE. The defects can be disclosed noninvasively by cardiopulmonary exercise testing.


Hip instability encountered in pediatric podiatry practice.
Infants and children with pathologic conditions of the foot and leg frequently have predictable comorbidity. The treating physician has the responsibility for identifying these associated problems and promptly referring if the problem is outside of his or her area of expertise. Hip dysplasia and dislocation occur frequently enough in association with congenital foot and leg deformity that they must be actively sought out in all cases. This article presents an overview of the topic, a review of screening protocols and appropriate imaging techniques and case studies of children with hip instability encountered in pediatric podiatry practice.


Modulation of enzymatic activities by n-3 polyunsaturated fatty acids to support cardiovascular health.
Epidemiological evidence from Greenland Eskimos and Japanese fishing villages suggests that eating fish oil and marine animals can prevent coronary heart disease. Dietary studies from various laboratories have similarly indicated that regular fish oil intake affects several humoral and cellular factors involved in atherogenesis and may prevent atherosclerosis, arrhythmia, thrombosis, cardiac hypertrophy and sudden cardiac death. The beneficial effects of fish oil are attributed to their n-3 polyunsaturated fatty acid (PUFA; also known as omega-3 fatty acids) content, particularly eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3). Dietary supplementation of DHA and EPA influences the fatty acid composition of plasma phospholipids that, in turn, may affect cardiac cell functions in vivo. Recent studies have demonstrated that long-chain omega-3 fatty acids may exert beneficial effects by affecting a wide variety of cellular signaling mechanisms. Pathways involved in calcium homeostasis in the heart may be of particular importance. L-type calcium channels, the Na+-Ca2+ exchanger and mobilization of calcium from intracellular stores are the most obvious key signaling pathways affecting the cardiovascular system; however, recent studies now suggest that other signaling pathways involving activation of phospholipases, synthesis of eicosanoids, regulation of receptor-associated enzymes and protein kinases also play very important roles in mediating n-3 PUFA effects on cardiovascular health. This review is therefore focused on the molecular targets and signaling pathways that are regulated by n-3 PUFAs in relation to their cardioprotective effects.


Positive and negative affective processing exhibit dissociable functional hubs during the viewing of affective pictures.
Recent resting-state functional magnetic resonance imaging (fMRI) studies using graph theory metrics have revealed that the functional network of the human brain possesses small-world characteristics and comprises several functional hub regions. However, it is unclear how the affective functional network is organized in the brain during the processing of affective information. In this study, the fMRI data were collected from 25 healthy college students as they viewed a total of 81 positive, neutral, and negative pictures. The results indicated that affective functional networks exhibit weaker small-worldness properties with higher local efficiency, implying that local connections increase during viewing affective pictures. Moreover, positive and negative emotional processing exhibit dissociable functional hubs, emerging mainly in task-positive regions. These functional hubs, which are the centers of information processing, have nodal betweenness centrality values that are at least 1.5 times larger than the average betweenness centrality of the network. Positive affect scores correlated with the betweenness values of the right orbital frontal cortex (OFC) and the right putamen in the positive emotional network; negative affect scores correlated with the betweenness values of the left OFC and the left amygdala in the negative emotional network. The local efficiencies in the left superior and inferior parietal lobe correlated with subsequent arousal ratings of positive and negative pictures, respectively. These observations provide important evidence for the organizational principles of the human brain functional connectome during the processing of affective information.


Over-expression of heme oxygenase-1 does not protect porcine endothelial cells from human xenoantibodies and complement-mediated lysis.
Accommodated organs can survive in the presence of anti-organ antibodies and complement. Heme oxygenase-1 (HO-1) is essential to ensure accommodation in concordant xenotransplant models. However, whether induction of HO-1 over-expression could protect porcine endothelial cells (PECs) against human xenoantibodies and complement-mediated lysis and induce an in vitro accommodation is still unknown. The SV40-immortalized porcine aorta-derived endothelial cell line (iPEC) was pre-incubated with 20, 50, or 80 μmol/L of cobalt-protoporphyrins IX (CoPPIX) for 24 h, and the HO-1 expression in iPECs was analyzed by using Western blotting. CoPPIX-treated or untreated iPECs were incubated with normal human AB sera, and complement-dependent cytotoxicity (CDC) was measured by both flow cytometry and lactate dehydrogenase (LDH) release assay. In vitro treatment with CoPPIX significantly increased the expression of HO-1 in iPECs in a dose-dependent manner. Over-expression of HO-1 was successfully achieved by incubation of iPECs with either 50 or 80 μmol/L of CoPPIX. However, HO-1 over-expression did not show any protective effects on iPECs against normal human sera-mediated cell lysis. In conclusion, induction of HO-1 over-expression alone is not enough to protect PECs from human xenoantibodies and complement-mediated humoral injury. Additionally, use of other protective strategies is needed to achieve accommodation in pig-to-primate xenotransplantation.


Cytogenetic investigations in childhood chronic myelocytic leukemia.
Cytogenetic studies were performed on 25 chronic myelogenous leukemia patients aged between 6 mo and 19 yr. Of these, 14 presented with the adult form and 11 with the juvenile form of the disease. In patients with the adult type, 12 of 14 had a Ph chromosome and additional anomalies appearing during blastic transformation. In patients with the juvenile form, 6 of 11 had a monosomy 7 and a short survival time (median 10 mo). Salient features of these patients, as well as a survey of the pertinent literature on the subject, are presented in this paper.


Monitoring of Thyroid Malfunction and Therapies in Pregnancy and the Postpartum Period: A Systematic Up-Dated Critical Review of the Literature.
From the very beginning of pregnancy, the maternal thyroid has to adapt to increased thyroid hormone secretion of up to 50 %. This is paralleled by changes in thyroid-stimulating-hormone (TSH) secretion and by the thyroid-topic action of human chorionic gonadotropin (hCG). Thus, hypothyroidism as well as hyperthyroidism may occur. Many women exhibit pre-existing thyroid diseases. This review tries to add the most recently published approaches to diagnosing thyroid malfunction in pregnancy to existing guidelines. Different literature-based approaches to diagnosing thyroid malfunction during pregnancy and the postpartum period were applied. To diagnose thyroid malfunction in pregnancy, trimester-specific reference ranges for TSH and T4 are used. Definitions of thyroid malfunction are given. Treatment schedules for various thyroid diseases were reviewed and, on the basis of recent findings, were revised where necessary. For a daily clinical work-up, this outline not only suggests diagnostic and therapeutic steps, but also refers to frequent pitfalls and misinterpretations of lab data. Although the body of knowledge is increasing rapidly, the authors believe that this review is able to present new ideas concerning diagnostic and therapeutic tools for thyroid malfunction in pregnancy and the postpartum period. Nevertheless, there seems to remain room for individual approaches based on the personal experience of physicians who deal with these issues regularly.


Early failure of long segment anterior cervical plate fixation.
A retrospective, multicenter study was undertaken to evaluate the early postoperative failure rate of long segment anterior cervical fusion and plating to stabilize the cervical spine after a two- or three-level corpectomy for degenerative, traumatic, and neoplastic diseases of the cervical spine. Patient demographic factors as well as technical factors such as bone graft placement, plate and screw position, and postoperative brace immobilization were analyzed. During the early postoperative period, the graft/plate construct dislodged in 3 of 33 patients with a two-level corpectomy and fusion (9%) compared with 6 of 12 patients with a three-level corpectomy and fusion (50%). The difference in failure rates after a three- versus two-level corpectomy and fusion was statistically significant (p < 0.05). A higher early failure rate was also seen with failure to correctly lock the screws to the plate and the use of a peg-in-hole type bone grafting technique, although these differences were not statistically significant. Although several technical and patient-specific factors may contribute to this, anterior cervical plating and bone grafting alone after a three-level cervical corpectomy for various spinal disorders appears to afford inadequate stability in the early postoperative period, regardless of immobilization methods.


Nanobody-Based Apolipoprotein E Immunosensor for Point-of-Care Testing.
Alzheimer's disease (AD) biomarkers can reflect the neurochemical indicators used to estimate the risk in clinical nephrology. Apolipoprotein E (ApoE) is an early biomarker for AD in clinical diagnosis. In this research, through bactrian camel immunization, lymphocyte isolation, RNA extraction, and library construction, ApoE-specific Nbs with high affinity were successfully separated from an immune phage display nanobody library. Herein, a colorimetric immunosensor was developed for the point-of-care testing of ApoE by layer-by-layer nanoassembly techniques and novel nanobodies (Nbs). Using highly oriented Nbs as the capture and detection antibodies, an on-site immunosensor was developed by detecting the mean gray value of fade color due to the glutaraldehyde@3-aminopropyltrimethoxysilane oxidation by H2O2. The detection limit of AopE is 0.42 pg/mL, and the clinical analysis achieves a good performance. The novel easily operated immunosensor may have potential application in the clinical diagnosis and real-time monitoring for AD.


Lattice instability and martensitic transformation in LaAg predicted from first-principles theory.
The electronic structure, elastic constants and lattice dynamics of the B(2) type intermetallic compound LaAg are studied by means of density functional theory calculations with the generalized gradient approximation for exchange and correlation. The calculated equilibrium properties and elastic constants agree well with available experimental data. From the ratio between the bulk and shear moduli, LaAg is found to be ductile, which is unusual for B(2) type intermetallics. The computed band structure shows a dominant contribution from La 5d states near the Fermi level. The phonon dispersion relations, calculated using density functional perturbation theory, are in good agreement with available inelastic neutron scattering data. Under pressure, the phonon dispersions develop imaginary frequencies, starting at around 2.3 GPa, in good accordance with the martensitic instability observed above 3.4 GPa. By structural optimization the high pressure phase is identified as orthorhombic B(19).


Epizootic congenital hydranencephaly and abortion in cattle due to bluetongue virus serotype 8 in the Netherlands.
An outbreak of hydranencephaly in aborted foetuses and newborn calves occurred following the 2007 epidemic of bluetongue serotype 8 (BTV8\net2006) in the Netherlands. In total 35 aborted foetuses and 20 live-born calves, submitted from September 2007 to May 2008, were examined pathologically. Foetuses with gestational ages between 4 and 9 months (mean 6.8 month) showed varying stages of cerebral malformation. Initial stages were cavitations in the cerebral hemispheres with massive destruction of neuroparenchyma, calcium deposits, and a phagocytic inflammatory response. Later stages showed distinct hydranencephaly, the cerebral hemispheres being almost completely replaced by fluid-filled sacs. In seven cases the cerebellum was affected as well, but brainstem structures were intact. Newborn calves with clinical signs of abnormal behaviour ('dummy calves'), circling, head pressing, incoordination, and blindness were seen from the end of January 2008. The calves were born between 2nd January and 16th March 2008. The calves were euthanized after 1 day up to 14 weeks (mean 4-7 weeks). Brain malformations in these calves were confined to the cerebrum and consisted of varying degrees of hydranencephaly. Spleen tissue was PCR-positive for bluetongue virus (BTV) in 21 of 35 foetuses and in 1 of 20 calves. A higher percentage of PCR-positives was found in foetuses aborted in early gestation than in late gestation, suggesting clearance of BTV during gestation. Fifteen of 33 dams of PCR-negative hydranencephalic foetuses or calves could be traced and all were BTV-seropositive, indicating a previous BTV infection. The timing of hydranencephaly cases in live-born calves during the first months of 2008 was consistent with infection in early gestation during the prior transmission season. Vertical transmission and teratogenic potential have previously been described for modified-live vaccines for bluetongue but are highly unusual for field strains of BTV, which raises the issue whether BTV8\net2006 or its ancestor has been cell- or laboratory-adapted in the past.


[Collections of human biological resources for research purposes: from regulations to the need of a guide of good collection practices].
In France, collections of human biological resources are regulated by the "Bioethics Law", currently in revision. Hence, we analyse the regulatory and ethical issues of these practices in the context of scientific research. The ultimate aim of such collections is to improve biological and medical knowledge. We think that the French regulatory system is quite complicated and non-explicit for "collection holders". The multiplicity of legal texts concerning this activity has made their application difficult, especially in the absence of application decrees. The project amending the actual law has clarified the legal status of collections but it did not shed light on the status of human body detached parts. Furthermore, the text is still very far from the international bioethical recommendations, and does not reflect the actual collection's implementation. The establishment of a guideline of Good Collection Practices, based on clear principles, should help to simplify the situation, especially when it is imbedded in the regulation and linked to control procedures. It would allow a balance between collective interests and the protection of individuals, taking into account of the international highly competitive scientific and economical constraints. The major issue is to preserve and to perpetuate the existing and future collections because of their precious value as an important tool for biomedical knowledge. The efficiency of a regulation depends on its legibility and accessibility, two requirements that seem to determine the acceptance of the regulatory tool and its application allowing subsequently to reach fairness in proceedings.


RAGE deficiency alleviates aortic valve calcification in ApoE-/- mice via the inhibition of endoplasmic reticulum stress.
Receptor for advanced glycation end products (RAGE) and endoplasmic reticulum (ER) stress have been shown to be involved in calcific aortic valve disease (CAVD). However, the association between RAGE and ER stress remains unknown in the pathogenesis of CAVD. The current study aims to test the hypothesis that RAGE deficiency alleviates aortic valve calcification via the inhibition of ER stress. Up-regulation of RAGE and ER stress markers in calcified human aortic valves were confirmed by immunoblotting. Aortic valve calcification was evaluated in atherosclerotic prone ApoE-/- mice or in mice with dual deficiencies of ApoE and RAGE (ApoE-/-RAGE-/-) fed with high cholesterol diet for 24weeks. Echocardiography and histological examination show that genetic deficiency of RAGE attenuates aortic valve calcification in ApoE-/- mice. Meanwhile, RAGE deficiency inhibited the osteogenic signaling and ER stress activation as well as suppressed macrophage infiltration in vivo. Cultured human aortic valve interstitial cells (AVICs) were treated with high molecular group box 1 protein (HMGB1) as in vitro model. We found that HMGB1 induced osteoblastic differentiation and calcification through RAGE/ER stress. Furthermore, Sox9 up-regulation and intranuclear translocation mediated the pro-osteogenic effect of HMGB1 on AVICs. RAGE or ER stress knockdown reduced the up-regulation of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in human AVICs exposed to HMGB1.These novel findings demonstrate that RAGE deficiency protects against aortic valve calcification in high cholesterol diet-fed ApoE-/- mice via inhibition of ER stress. HMGB1 induces AVIC osteoblastic differentiation and calcification through RAGE/ER stress/Sox9 pathway.


Required steps for the validation of a Laboratory Information Management System.
The task of managing laboratory data is not a new one. Over the past two decades, the use of Laboratory Information Management Systems (LIMS) has revolutionized how laboratories manage their data. A LIMS is more than software; it has become the workhorse of the laboratory, encompassing laboratory work-flow combined with user input, data collection, instrument integration, data analysis, user notification, and delivery of information and reporting. Types of organizations that utilize LIMS vary greatly from research laboratories to manufacturing laboratories to environmental testing laboratories. Commercially-available LIMS have been around since the 1980s. In addition, many laboratories have designed, implemented, and maintained in-house LIMS. The heart of any LIMS is the software. Like other laboratory systems, the LIMS software is subject to quality control and quality assurance checks. In regulatory environments this associated QA/QC is referred to as "system validation." The primary purpose of system validation is to ensure that the software is performing in a manner for which it was designed. For example, the system acceptance criteria should be established and tested against quantifiable tasks to determine if the desired outcome has been achieved. LIMS features, such as autoreporting, reproducibility, throughput, and accuracy must be quantifiable and verifiable. System validation ensures that the entire system has been properly tested, incorporates required controls, and maintains and will continue to maintain data integrity. Laboratories must establish protocols and standards for the validation process and associated documentation. Although vendors of commercial LIMS perform initial internal system validations, the system must be revalidated whenever the end user, vendor or third party adds modifications or customizations to the LIMS. Currently, detailed guidance regarding system validation of LIMS is not available to the user. The issue is addressed in Good Automated Laboratory Practices (GALP) and National Environmental Laboratory Accreditation Conference (NELAC) documents which indicate specific requirements or recommendations for operational checks and periodic testing; however, it is up to the laboratory to determine suitable methods to accomplish these tasks. Proper validation of a LIMS will allow a laboratory to comply with regulations and also provide comprehensive documentation on the system that is necessary to troubleshoot future problems.


Impact of a formulary switch from ticarcillin-clavulanate to piperacillin-tazobactam on colonization with vancomycin-resistant enterococci.
The prevalence of vancomycin-resistant enterococci (VRE) is increasing, despite infection control measures. Limited data link ticarcillin-clavulanate to higher VRE prevalence. Active surveillance for VRE was conducted before and after a formulary switch from ticarcillin-clavulanate to piperacillin-tazobactam. Rectal swabs were obtained serially in 863 adult patients admitted to intensive care units (ICUs) between November 1, 2000 and September 30, 2004. In the postswitch period, 38 of 497 (7.6%) patients acquired VRE versus 42 of 366 (11.5%) patients in the preswitch period. Survival analysis showed an overall hazard ratio (HR) of .68 postswitch versus preswitch ( P = .07), with the greatest change in the surgical ICU (HR = .17, P = .006). Multivariate analysis showed an overall HR = .51 ( P = .004). Hospital-wide, nonstool VRE clinical cultures fell from 39 (.58/1000 patient days) in the 10-month preswitch period to 27 (.33/1000 patient days) in the 12-month postswitch period. Infection control practices and use of other antibiotics remained stable. VRE acquisition appeared to decrease in association with a formulary change from ticarcillin-clavulanate to piperacillin-tazobactam.


Establishment of dsDNA/GNs/chit/GCE biosensor and electrochemical study on interaction between 6-mercaptopurine and DNA.
In this paper, the anti-cancer drug 6-mercaptopurine (6-MP) was taken as the detection object. The biosensor of dsDNA/GNs/chit/GCE was established using the grapheme (GNs) and chitosan (chit) as the compound modified material. The electrochemical behavior of 6-MP on the sensor was discussed, and the damage and its mechanism of 6-MP on DNA were studied. The experimental result showed that, after the modification of GNs-chit, the electrode activation area of GNs/chit/GCE increased remarkably, which was improved from 1.76cm2 to 8.64 cm2, and the responsive oxidation peak current of GNs/chit/GCE to K3[Fe(CN)6] also increased remarkably. At the meantime, it was demonstrated that DNA was effectively fixed on the GNs/chit/GCE electrode;6-MP caused obvious damage to dsDNA, and the damage degree on the adenine was bigger than that on the guanine; the interaction between 6-MP and dsDNA was preliminarily deduced as the intercalation, and its electrochemical oxidation process was an irreversible process controlled by the adsorption.


Credentialing complementary and alternative medical providers.
Since the late 19th century, state legislatures and professional medical organizations have developed mechanisms to license physicians and other conventional nonphysician providers, establish standards of practice, and protect health care consumers by establishing standardized credentials as markers of competence. The popularity of complementary and alternative medical (CAM) therapies presents new challenges. This article describes the current status of, and central issues in, efforts to create models for health care credentialing of chiropractors, acupuncturists, naturopaths, massage therapists, and other CAM practitioners. It also suggests a strategy of CAM provider credentialing for use by physicians, health care administrators, insurance companies, and national professional organizations. The credentialing debate reflects fundamental questions about who determines which providers and therapies will be accepted as safe, effective, appropriate, and reimbursable. More nationally uniform credentialing mechanisms are necessary to ensure high standards of care and more generalizable clinical research. However, the result of more uniform licensure and credentialing may be excessive standardization and a decrease in individualization of services. Thus, increased standardization of credentialing for CAM practitioners may alter CAM practice substantially. Furthermore, even credentialed providers can deliver ineffective therapy. The suggested framework balances the desire to protect the public from dangerous practices against the wish to grant patients access to reasonably safe and effective therapies.


Viscoelastic properties of the rat brain in the sagittal plane: effects of anatomical structure and age.
Rat is the most commonly used animal model for the study of traumatic brain injury. Recent advances in imaging and computational modeling technology offer the promise of biomechanical models capable of resolving individual brain structures and offering greater insight into the causes and consequences of brain injury. However, there is insufficient data on the mechanical properties of brain structures available to populate these models. In this study, we used microindentation to determine viscoelastic properties of different anatomical structures in sagittal slices of juvenile and adult rat brain. We find that the rat brain is spatially heterogeneous in this anatomical plane supporting previous results in the coronal plane. In addition, the brain becomes stiffer and more heterogeneous as the animal matures. This dynamic, region-specific data will support the development of more biofidelic computational models of brain injury biomechanics and the testing of hypotheses about the manner in which different anatomical structures are injured in a head impact.


The radiographic density of composite restorative resins.
The radiodensities of enamel, dentin, aluminum, and 14 modern composite resins at thicknesses of 1 to 4 mm were compared. Nine of the 14 composites were radiopaque with respect to that of aluminum. Radiolucent lesions or voids were simulated by cutting grooves 0.5, 1.0, and 2.0 mm deep in aluminum stepwedge blocks, superimposing stepwedges of the radiopaque composites over the blocks, and radiographing the combination. It was found that only five of the nine radiopaque composite materials possessed radiodensities that permitted clear radiographic detection of the smaller defects.


Obstetric balloon for treatment of foreshortened vagina using the McIndoe technique.
When conservative options such as the use of vaginal dilators fail, the McIndoe technique may be used in the surgical treatment of a foreshortened vagina. The McIndoe procedure, an approach commonly used for the treatment of vaginal agenesis, requires a mold over which a skin graft is sutured and placed inside the vagina. In most surgical descriptions, this mold is made from non-sterile foam, condoms, or gloves. Because makeshift molds can no longer be used in operating rooms owing to strict regulations, alternative methods must be employed. The obstetric balloon is a good choice for use as a soft and adjustable vaginal mold for a modified McIndoe procedure because it is readily available as an approved device in hospitals that provide obstetric services. This technique was successfully employed in a 54-year-old woman to treat foreshortened vagina. An obstetric balloon can be used effectively as a mold for vaginal reconstruction with the McIndoe technique.


Is immunity to malaria really short-lived?
Protection against Plasmodium falciparum malaria is usually considered to be the cumulative product of repeated exposure to parasites, and thus a function of age, in endemic areas. The recent outbreak of malaria in the central highlands of Madagascar gave Philippe Deloron and Claire Chougnet the opportunity to compare the incidence of malaria in children and young adults exposed to malaria for the first time, with that in older adults who spent their childhood in the study area before malaria control was introduced. Protection, as well as immune responses to two major P. falciparum antigens, was not related to age. Individuals older than 40 years were more protected than were younger adults. This increased protection was probably due to immunological memory.


Optimization of a multi-gene HIV-1 recombinant subtype CRF02_AG DNA vaccine for expression of multiple immunogenic forms.
We developed an AIDS vaccine for Western and West-Central Africa based on a DNA plasmid vector expressing HIV-1 recombinant subtype CRF02_AG gag, pol, and env genes. To optimize the production of noninfectious HIV-like particles (VLPs) and potentially improve the effectiveness of the vaccine, we generated four potential vaccine constructs: the parental (IC2) and three modifications (IC25, IC48, and IC90) containing mutations within the HIV protease. While the parental construct IC2 expressed aggregates of Gag proteins, the IC25 construct resulted in the production of immature VLPs (the core comprises unprocessed Pr(55Gag)). The remaining two constructs (IC48 and IC90) produced mature VLPs (the core comprises processed capsid p24) in addition to immature VLPs and aggregates of Gag proteins. VLPs incorporated significant levels of mature gp120 envelope glycoprotein. Importantly, the mature VLPs were fusion competent and entered coreceptor-specific target cells. The production of multiple antigenic forms, including fusion-competent VLPs, by candidate DNA vaccine constructs may provide immunologic advantages for induction of protective cellular and humoral responses against HIV-1 proteins.


Malignant mediastinal germ cell tumor with pure hepatoid differentiation.
We describe a germ cell tumor of anterior mediastinal origin, with pure hepatoid differentiation and elevated serum AFP in a 41-year-old man. This is the first report of such a neoplasm analyzed by conventional stains and immunohistochemistry. Hepatocellular differentiation was proved by immunoreactivity with HepPar-1 and alpha-fetoproein (AFP), membranous expression of carcinoembryonic antigen (CEA-poly) in a canalicuar pattern, and focal expression of cytokeratin 19 in abortive ductular structures. Our investigation shows that mediastinal germ cell tumors with hepatoid components typically arise in middle-aged men; they are of pure hepatoid differentiation, as demonstrated here, or exclusively associated with yolk sac structures.


Competency-based education in thrombolytic therapy: a modular approach.
Continuing education of nurses in therapeutic advancements poses a challenge to nurse educators and managers. The competency-based educational method is a way to prepare nurses and subsequently evaluate performance based on derived standards. In this article a competency-based education approach to the use of thrombolytic therapy in acute myocardial infarction is examined.


Association of polymorphism of LTalpha and TNF genes with Graves' disease.
Graves' disease (GD) is an autoimmune disease, which develops on the basis of an interaction between genetic, environmental and endogenous factors. GD is associated with some HLA genes. Closely linked with them are TNF genes (TNF and LTalpha). Their role in the pathogenesis of GD is still unclear. Two functional polymorphisms within TNF genes include a substitution of G with A in intron I of LTalpha gene and the same one at position -308 in the TNF gene promoter. We carried out a case-control study for the analysis of the contribution of TNF genes to GD in Polish patients. 156 patients with GD diagnosed by clinical data were investigated and compared to 80 healthy persons with negative familial anamnesis. Both TNF and LTalpha were analysed by PCR/Nco I RFLP. The allelic frequency of the rarer TNF2 (A) allele, was 24.7% in GD patients, significantly higher than in healthy persons (9.3%; p<0.0001). The OR was 4.38 for this allele. The frequency of heterozygotes was 41.8% in GD, as compared to 13.6% in the control group. The allelic frequency of the rarer LTB*1 (G) allele was also significantly increased: from 21.9% in the control group to 37.2% in GD patients (p<0.01; OR 2.81). The frequency of heterozygotes was 48.7% in GD, and 28.8% in the control group. The results indicate that TNF genes may contribute to GD in the Polish population.


[Significance of identification of fungi in gastric juice of patients with artificial airway in intensive care unit].
To investigate the direct relationship and significance between the pH value of gastric juice and positive fungi in culture critical patients with artificial airway in intensive care unit (ICU) by analyzing and identifying the type of fungi and their sensitivity to antifungal therapy. A prospective study was conducted.One hundred and sixty patients (between December, 2008 and October, 2011) with artificial airway lasting longer than 48 hours were studied in the ICU at the First Affiliated Hospital of Shenzhen University. The gastric juice specimens were collected through a nasogastric tube, their pH values were measured using precise litmus paper. These samples were divided into six groups according to their pH values: pH ≤ 2.0, pH 2.1-3.0, pH 3.1-4.0, pH 4.1-5.0, pH 5.1-6.0 and pH 6.1-7.0, and then fungi were cultured in these specimens with different pH values. Susceptibility of different fungicide drugs were also investigated. The susceptibility of fungi to gastric juice with different pH values was also investigated. The relationship between 28-day survival rate and the presence of fungi in gastric juice was analyzed in order to analyze the relationship of the presence of fungi in gastric juice and clinical outcome. (1) No fungal growth was found in the gastric juice with pH value lower than 4.0, and the positive rate of fungal culture was significantly increased when the pH value of gastric juice raised. (2) The positive rate of fungal growth was 27.9% (55/197), in which, the positive rate of Candida and non-Candida fungi was 38.2% (21/55) and 61.8% (34/55) respectively, and the difference was significant statistically [χ(2) = 4.16, P < 0.05]. (3) The fungal positive rate was 40.0% (22/55) and 60.0% (33/55) respectively, in survivors (102 cases) and non-survivors (58 cases). The percentage of Candida infection and non-Candida infection was 54.5% (12/22) and 45.5% (10/22) respectively, in survivors, and it was 27.3% (9/33) and 72.7% (24/33), respectively, in non-survivors. The rate of resistance of Candida and non-Candida fungi was 4.7%-14.3% (mean 10.1%) and 0-60% (mean 28.5%) respectively. Positive fungus culture rate was higher in critical patients with artificial airway and higher gastric juice pH values. Non-Candida fungi were mainly found in gastric juice with increasing resistance rate. Candida was more commonly found in survivors, and non-Candida fungi were more commonly found in non-survivors.


The VER as a predictor of normal visual acuity in the adult human eye.
The ability of the evoked potential to predict conventional visual acuity, as measured with a Landolt C test, was investigated for subjects with normal acuities. Both peak-to-trough and Fourier-analysed amplitudes were used. The extrapolation technique assumed curvilinear regression and produced correlations no better than did a method employing amplitude measurements of a single check size of 5.5 min arc (r = 0.67). Assessment of Landolt C acuity by subjective use of the evoked potential stimulus was unable to produce a higher correlation.


Primary upper-extremity deep vein thrombosis: high prevalence of thrombophilic defects.
Primary deep venous thrombosis of the upper extremity (UEDVT) is an unusual disorder. Limited data are available on the contribution of hypercoagulable status in the pathogenesis of this disease. This study aims to report the prevalence of inherited and acquired thrombophilic risk factors (TF) in patients with primary (effort-related and spontaneous) UEDVT. From 1993 to 2002, 31 patients (17 females, median age 38.8 years, range 16-60 years; and 14 males, median age 31.4 years, range 20-56 years) with primary UEDVT (n = 15 effort-related and n = 16 spontaneous) were referred for screening of hypercoagulable status. Nineteen (61.3%) patients had at least one coagulation abnormality. The most common acquired TF were antiphospholipid antibodies (31% lupus anticoagulant and 12.9% anticardiolipin antibodies). Factor V Leiden (12.9%) and prothrombin G20210A mutation (20%) were the most prevalent genetic risk factors. Five patients (16.1%) had high plasma homocysteine levels, and one patient (4.7%) had protein S deficiency. Effort-related UEDVT was associated with male gender (P = 0.04) and younger age (P = 0.02). There was no significant difference in the prevalence of acquired or inherited TF between patients with effort-related or spontaneous UEDVT. A local anatomic abnormality was detected in seven patients (22.5%), and the prevalence of TF was significantly lower within this group (P = 0.006). The incidence of TF in patients without an anatomic abnormality was 75% (RR 5.25). This study found a high prevalence of an underlying thrombophilic status in spontaneous and effort-related UEDVT. Hypercoagulable status may play a significant role in both groups. Screening for local anatomical abnormalities and thrombophilia should be included in the evaluation of primary UEDVT.


The level of phosphorylated Akt predominantly reflects the expressive status of CerbB2 in invasive breast cancer.
Although some evidence has been documented on EGFR/PI3K mediation of Akt activation in breast cancers, ILK and DNA-PK have not been investigated so far. The aim of this study was to analyze the expression of phosphorylated Akt (pAkt) in breast cancer, with respect to its upstream regulators. The immunostaining of pAkt (Ser473) in 70 invasive breast cancers revealed that status of CerbB2 could play a major role in Akt phosphorylation, while ILK was also involved in the stimulated level of pAkt. The results would provide an important clue for the activation of Akt and potential targeted therapy in breast cancer.


Projection structure of the bacterial oxalate transporter OxlT at 3.4A resolution.
OxlT is a bacterial transporter protein with 12 transmembrane segments that belongs to the Major Facilitator Superfamily of transporters. It facilitates the exchange of oxalate and formate across the membrane of the Gram-negative bacterium Oxalobacter formigenes. From an electron crystallographic analysis of two-dimensional, tube-like crystals of OxlT, we have previously determined the three-dimensional structure of this transporter at 6.5 A resolution. Here, we report conditions to obtain crystalline, two-dimensional sheets of OxlT with diameters exceeding 2 microm. Images of the crystalline sheets were recorded at liquid nitrogen temperatures on a transmission electron microscope equipped with a field-emission gun, operated at 300 kV. Computed optical diffraction patterns from the best images display measurable reflections to about 3.4A, and electron diffraction patterns show spots to about 3.2 A resolution in the best cases. As in the case of the tube-like crystals, the new crystalline sheets also belong to the p22(1)2(1) symmetry group. However, the unit cell dimensions of 102.7A x 67.3 A are significantly smaller in one direction than those previously observed with the tube-like crystals that display unit cell dimensions of 100.3A x 79.0 A. Different regions of OxlT are involved in intermolecular contacts in the two types of crystals, and the improved resolution of the sheet crystals appears to be mainly attributable to this tighter packing of the monomers within the unit cell.


An analysis of workplace exposures to asbestos at three steel mills located in the United States (1972-1982).
The objective is to present historical asbestos airborne concentrations associated with activities involving presumably asbestos-containing materials in steel mills. A total of 138 historical industrial hygiene air samples collected in three US steel mills from 1972 to 1982 were analyzed. The majority of samples were collected during relining of open hearth furnaces, stoves, and blast furnaces by steel mill bricklayers and bricklayer helpers. Over 75% of the samples (n = 106) were collected for 50 min or less, four samples were collected for 227 to 306 min, and sample durations were not reported for the remaining 28 samples. Average airborne fiber concentrations measured during relining activities of open hearth furnaces, stoves, and blast furnaces were 0.21 f/cc, 0.72 f/cc and 0.13 f/cc phase-contrast microscopy (PCM), respectively. Measured airborne fiber concentrations of four time-weighted average (TWA) samples (>227 min) averaged 0.045 f/cc. Estimated 8-h TWAs concentrations averaged 0.34 f/cc for bricklayers and 0.2 f/cc bricklayer helpers. While 8-h TWA concentration estimates for monitored tasks/jobs may often have exceeded current Occupational Safety and Health Administration (OSHA) Permissible Exposure Limits (PELs), they did not exceed relevant contemporaneous occupational exposure standards. This analysis provides a better understanding of historical airborne asbestos exposures that bricklayers and other tradesmen experienced during furnace and stove work in the US steel mills.


Suction lipectomy preceding pregnancy and postpartum results.
A retrospective case-control study was undertaken to determine if women who have undergone suction lipectomy of the abdomen, flanks and lower extremities suffer any reversal of the beneficial results of the procedure as a result of a subsequent term pregnancy and parturition. Cases with two women subjects who became pregnant and experienced full-term pregnancies and healthy childbirth shortly following suction lipectomy of the torso and lower extremities are reviewed. Bodily measurements about significant planes were recorded prior to suction lipectomy, between suction lipectomy and pregnancy, and 32 weeks postpartum. Controls included three women patients who did not become pregnant following the surgery, for whom similar measurements were available pre-suction lipectomy and post-suction lipectomy at short-term and long-term follow-up. The hiatus between follow-ups allowed for a potential gestational period to match the two cases. Results showed insignificant, if any, change between measurements before and after pregnancy in cases; in controls, excellent agreement was also achieved between measurements taken post-surgically at short-term and at long-term follow-up. Assuming normal gravid weight gain and maintenance of proper diet following pregnancy, measurements achieved by suction lipectomy are unaffected by pregnancy and parturition.


Biosurfactants and surfactants interacting with membranes and proteins: Same but different?
Biosurfactants (BS) are surface-active molecules produced by microorganisms. For several decades they have attracted interest as promising alternatives to current petroleum-based surfactants. Aside from their green profile, they have remarkably low critical micelle concentrations, reduce the air/water surface tension to very low levels and are excellent emulsifiers, all of which make them comparable or superior to their synthetic counterparts. These remarkable physical properties derive from their more complex chemical structures in which hydrophilic and hydrophobic regions are not as clearly separated as chemical surfactants but have a more mosaic distribution of polarity as well as branched or circular structures. This allows the lipopeptide surfactin to adopt spherical structures to facilitate dense packing at interfaces. They are also more complex. Glycolipid BS, e.g. rhamnolipids (RL) and sophorolipids, are produced biologically as mixtures which vary in the size and saturation of the hydrophobic region as well as modifications in the hydrophilic headgroup, such as the number of sugar groups and different levels of acetylation, leading to variable surface-active properties. Their amphiphilicity allows RL to insert easily into membranes at sub-cmc concentrations to modulate membrane structure and extract lipopolysaccharides, leading to extensive biofilm remodeling in vivo, sometimes in collaboration with hydrophobic RL precursors. Thanks to their mosaicity, even anionic BS like RL only bind weakly to proteins and show much lower denaturing potency, even supporting membrane protein refolding. Nevertheless, they can promote protein degradation by proteases e.g. by neutralizing positive charges, which together with their biofilm-combating properties makes them very promising detergent surfactants. This article is part of a Special Issue entitled: Lipid order/lipid defects and lipid-control of protein activity edited by Dirk Schneider.


Ischemic cholangiopathy.
Bile ducts are supplied with blood exclusively via hepatic arteries. Obstruction of large arteries is rapidly compensated for by the opening of preexisting intrahepatic or transcapsular collateral arteries, which prevents ischemic damage. Ischemic bile duct injury may occur when small hepatic arteries or the peribiliary vascular plexus are injured, or when all possible arterial blood supplies are interrupted, as is the case in transplanted liver with hepatic artery thrombosis. Most causes of bile duct ischemia are iatrogenic. Systemic diseases involving small hepatic arteries may also be implicated. Depending on the extent and velocity of the arterial obstructive process, ischemic cholangiopathy may present as acute formation of biliary casts, bile duct necrosis, or chronic disease resembling primary sclerosing cholangitis. In many patients, correction of arterial obstruction is not possible. When biliary drainage or reconstruction is not possible or has failed, liver transplantation is the only means of providing potential cure.


Gas to olive oil partition coefficients: a linear free energy analysis.
Literature values of gas to olive oil partition coefficients at 37 degrees C have been assembled for 218 compounds. Application of an Abraham linear free energy equation correlates 215 compounds with R2=0.981 and a standard deviation, SD, of 0.196 log units. One hundred and eight compounds were then used as a training set, and the resulting equation was used to predict the remaining 107 compounds with an average error of 0.025, an absolute average error of 0.150, and a standard deviation of 0.224 log units. The linear free energy equation shows that as a solvent olive oil is not very polar but is reasonably basic, although with a weaker hydrogen bond base than ethyl acetate or acetone, and has no hydrogen bond acidity. The coefficients for partition from the gas phase to biological phases such as blood and brain lie between those for water and olive oil, which explains why gas to biological phase partition can be described in an empirical way by a combination of gas to olive oil and gas to saline coefficients.


Plasmodium knowlesi malaria in Malaysia.
Plasmodium knowlesi, a simian malaria parasite, is now recognised as the fifth cause of human malaria and can lead to fatal infections in humans. Knowlesi malaria cases are widely distributed in East and West Malaysia and account for more than 50% of admissions for malaria in certain hospitals in the state of Sarawak. This paper will begin with a description of the early studies on P. knowlesi, followed by a review of the epidemiology, diagnosis, clinical and laboratory features, and treatment of knowlesi malaria.


Mind-body medicine in primary care. Implications and applications.
A growing body of research in basic and clinical science confirms that psychological states and interventions affect physiologic and pathophysiologic processes and the outcome of clinical illness. This evidence is reviewed in detail, with special attention paid to those findings that have particular relevance for primary care physicians. Specific guidelines are offered for incorporating mind-body principles and techniques into primary care practice.


Impact of pulsatile perfusion on postoperative outcome of kidneys from controlled donors after cardiac death.
Pulsatile perfusion (PP) might be a cost-effective cold preservation technique to reduce the incidence of delayed graft function (DGF) in kidneys from deceased donors. With the aim to address whether PP can reduce the incidence of DGF in kidneys from controlled donors after cardiac death (cDCD), we compared the clinical outcome of 30 recipients of kidneys from cDCD preserved by static cold storage (cDCD-SCS) with 30 recipients of cDCD kidneys preserved by PP (cDCD-PP). The end-points were the incidence of primary nonfunction (PNF), DGF and acute rejection (AR), the length of hospitalization, 1, 3, 6 and 12-months graft function, graft survival and patient survival. Donor, recipient and preimplantation data were well matched. DGF was significantly lower (53.3% vs. 86.6% P<0.001) and the length of hospitalization shorter (10 vs. 14 days P<0.033) in the cDCD-PP group. Similarly, postoperative and short-term graft function (7 and 30 days and 6 and 12 months, respectively) was statistically better in the cDCD-PP than in the cDCD-SCS. In summary, in this cohort, clinical introduction of PP was associated with a significant reduction of DGF, shorter hospitalization and better graft function than SCS.


Mass spectrometric analysis of DNA mixtures: instrumental effects responsible for decreased sensitivity with increasing mass.
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has demonstrated great potential to replace gel electrophoresis for DNA sequence analysis. A current limitation in this method is, however, the decreased sensitivity with increasing mass of DNA molecules. In the present study, instrumental effects on the mass analysis of DNA molecules were investigated quantitatively using an equimolar DNA mixture. It is shown that detection efficiency, detector saturation, and ion beam divergence account for the entirety of the observed falloff in signal intensity with increasing mass. Although the present study focused upon the analysis of DNA mixtures, the instrumental effects observed apply equally to other macromolecular mixtures (e.g., proteins, polymers).


Outcomes of arteriovenous fistulae created by a U.S. interventional nephrologist.
Arteriovenous fistulae (AVF) outcomes in the United States continue to fall short of expectations and continue to compare disfavorably to European AVF outcomes. This study presents the early experience of nephrologist created AVF outcomes in the U.S. hemodialysis population. A retrospective analysis of a prospectively collected vascular access database was performed. All patients who were referred for vascular access placement over a 1-year period were eligible for inclusion. One hundred five (n = 105) patients were initially included in the database. An AVF was placed in 100% of patients referred for vascular access. Two complications were identified (one steal syndrome and one infection) for a rate of 1.9%. The patient demographics included 38.7% female, age 63.6 + or - 14.8, 50.0% diabetic, 66.0% hypertensive, with 65.1% of patients in stage 5 chronic kidney disease at the time of AVF placement. Average target artery diameter was 4.09 + or - 1.16 mm while average target vein diameter was 3.66 + or - 1.20. Twenty-one AVF were placed in the forearm (19.8%) with the remainder being placed in the upper arm vessels. Eighteen patients (18.56%) failed to mature at 6 weeks. Sixty-four patients (65.98%) required revision or intervention of their AVF between 12 weeks postoperatively and the endpoint of the study. Eighty patients (84.21%) had patent AVF at an average follow-up of 286.2 + or - 98.14 days. No identifiable risk factors among those listed above were associated with a significant impact on AVF outcomes. AVF outcomes that compare favorably to those of Europe can be achieved by U.S. interventional nephrologists. Furthermore, the dictum that distal is better needs to be re-examined if the United States hopes to achieve the goal of 66% AVF prevalence.


Genetic variation analysis of Mugil cephalus in China sea based on mitochondrial COI gene sequences.
In this study, genetic diversity and population genetic structure of flathead grey mullet, Mugil cephalus, among four China Sea populations were investigated by COI sequences. All the populations studied had high values of haplotype and nucleotide diversity, except for the Yellow Sea population. In the phylogenetic tree, these haplotypes clustered in two groups, one for the populations from the Bohai and East China seas, and the other from the Yellow and South China seas. Analysis of molecular variance indicated that the northern populations (Bohai and East China) had lower genetic divergence (0.0725, P > 0.05) than that of the southern population (South China) (0.4530-0.6827, P < 0.001), suggesting that two distinct genetic groups exist in Chinese waters. Tests of neutral evolution and mismatch distribution indicated that no historical demographic expansion occurred in these populations. The results provide new information for genetic assessment, fishery management, and conservation of this species.


Trimethoprim/sulfamethoxazole desensitization.
Although alternative therapy for PCP remains limited, the role of TMP/SMX desensitization becomes increasingly important in patients with AIDS. Various successful desensitization protocols have been described in this article. As there are no established guidelines, it appears that the desensitization procedure can occur in small successive doses given each day or one small dose given daily. An evaluation of the severity of allergic reaction can be used to determine the type of dosing regimen. We believe that protocols starting with low doses and slow titration to full-dose therapy, as used at our institution, should be efficacious. Monitoring of the patient after the desensitization procedure should continue, as sensitivity may reoccur. In addition, while the patient is undergoing desensitization, some investigators recommend that alternative therapy be continued until full-dose TMP/SMX therapy is achieved. Also, it is important to realize that once a patient is successfully desensitized, medication compliance must be maintained because, theoretically, reexposure to the drug after a lapse in therapy may result in hypersensitivity reactions. Therefore, this procedure and the possibility of serious adverse effects, such as Stevens-Johnson syndrome and anaphylaxis, should be evaluated carefully and discussed thoroughly with each patient prior to initiation of therapy. Finally, a study of sufficient size should be performed to evaluate the efficacy of desensitization regimens and establish specific dosing guidelines.


Replacement of mitral, aortic, and pulmonary valves for rheumatic heart disease.
Rheumatic disease of the pulmonary valve has been documented at autopsy. Most of the reported cases of calcified pulmonary valves are associated with congenital heart disease. A unique case of rheumatic aortic and mitral valve disease associated with calcific pulmonary stenosis is presented. Prosthetic replacement of all three involved valves was carried out successfully. This is believed to be the first reported triple valve replacement of its kind.