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Egg freezing: a breakthrough for reproductive autonomy? | This article describes the relatively new technology of freezing human eggs and examines whether egg freezing, specifically when it is used by healthy women as 'insurance' against age-related infertility, is a legitimate exercise of reproductive autonomy. Although egg freezing has the potential to expand women's reproductive options and thus may represent a breakthrough for reproductive autonomy, I argue that without adequate information about likely outcomes and risks, women may be choosing to freeze their eggs in a commercially exploitative context, thus undermining rather than expanding reproductive autonomy. | 18,945,249 |
Perinatal risk factors and coeliac disease in children and young adults: a record linkage study. | Little is known about perinatal risk factors and coeliac disease. To investigate the relationship between perinatal risk factors and subsequent coeliac disease among offspring. Record linked abstracts of birth registrations, maternity, in-patient and day case records in a defined population of southern England. Using univariate analysis, coeliac disease in the child was associated with maternal coeliac disease (odds ratio = 20.6; 95% CI = 5.04-84.0; based on two cases in both mother and child) and with social class, year of birth, maternal smoking and parity. Multivariate analysis confirmed an increased risk of coeliac disease of 3.79 (95% CI = 1.85-7.79) for classes IV and V compared with I and II, an increased risk of 1.92 (1.06-3.49) for births during 1975-1979 compared with 1970-1974 and an increased risk of 1.80 (1.05-3.09) for 'subsequent' compared with 'first' births. Smoking during pregnancy was no longer associated with coeliac disease. Because numbers were small, maternal coeliac disease was excluded from the multivariate analysis. This study shows increased risks of coeliac disease for manual social classes, births during the late 1970s and 'subsequent' births. Overall, perinatal risk factors seem to have a limited role in the aetiology of coeliac disease in children and young adults. | 18,945,253 |
Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis. | Non-alcoholic steatohepatitis (NASH) is a form of progressive fatty liver disease that is strongly associated with insulin resistance, which suggests that insulin sensitizing agents such as metformin may be beneficial for NASH. To assess the effects of metformin on insulin sensitivity, body composition, serum alanine aminotransferase (ALT) levels and liver histology in patients with NASH. Patients underwent liver biopsy, metabolic profiling and imaging studies before and at the end 48 weeks of metformin (2000 mg/day) therapy. The primary endpoint was a three-point improvement in the histological NASH activity index. Of 28 patients enrolled, 26 (13 females; average age 44 years) completed 48 weeks of treatment and underwent repeat metabolic studies, imaging and liver biopsy. Thirty per cent achieved a histological response. Most patients lost weight, the average being 6 kg. There was a marked association between weight loss and improvements in NASH activity index and ALT levels (both, P < 0.01). Insulin sensitivity also improved, but the degree of change did not correlate with histological improvement. Metformin leads to improvements in liver histology and ALT levels in 30% of patients with NASH, probably by its effects in causing weight loss. | 18,945,255 |
An open study of antibiotics for the treatment of pre-pouch ileitis following restorative proctocolectomy with ileal pouch-anal anastomosis. | Pre-pouch ileitis is a recently described condition which may occur following restorative proctocolectomy. Its aetiology remains unknown and only one study has reported the effect of treatment. We report a series of fourteen patients treated and followed up with repeat pouchoscopy. To study the effectiveness of antibiotics for the treatment of pre-pouch ileitis following restorative proctocolectomy with ileal pouch-anal anastomosis. Fourteen consecutive patients with symptomatic pre-pouch ileitis were treated with ciprofloxacin 500 mg b.d. and metronidazole 400 mg b.d. for 28 days. All had concurrent pouchitis. Symptomatic, endoscopic and histological assessment was performed before and following treatment using the pouchitis disease activity index (PDAI). Symptomatic remission was defined as a score of 0 in the clinical component of the PDAI. Twelve (86%) patients experienced symptomatic remission. Stool frequency fell from a median of 12 (range 8-20) to 6 (4-17) (P = 0.002). There was a significant reduction in the anatomical length of pre-pouch ileitis with nine (64%) patients having either a resolution or a reduction in length of pre-pouch ileitis from a median of 10 cm (range 3-20 cm) to a median of 1 cm (range 0-10 cm) (P = 0.007). Combination antibiotic therapy in this uncontrolled study appears effective in reducing the length of pre-pouch ileitis and in inducing symptomatic remission in most patients whether or not its extent is reduced. | 18,945,262 |
Cerebral tissue oxygenation index and superior vena cava blood flow in the very low birth weight infant. | Superior vena cava (SVC) flow assesses blood flow from the upper body, including the brain. Near infrared spectroscopy (NIRS) provides information on brain perfusion and oxygenation. To assess the relationship between cerebral tissue oxygenation index (cTOI) and cardiac output measures in the very low birth weight (VLBW) infant in the first day of life. A prospective observational cohort study. Neonates with birth weight less than 1500 g (VLBW) were eligible for enrollment. Newborns with congenital heart disease, major congenital malformations and greater than Papile grade1 Intraventricular Haemorrhage on day 1 of life were excluded. Echocardiographic evaluation of SVC flow was performed in the first 24 h of life. Low SVC flow states were defined as a flow less than 40 mL/kg/min. cTOI was measured using NIRO 200 Hamamatsu. Twenty-seven VLBW neonates had both echocardiography and NIRS performed. The median (range) gestation was 29/40 (25 + 3 to 31 + 5 weeks) and median birth weight was 1.2 kg (0.57-1.48 kg). The mean (SD) TOI was 68.1 (7.9)%. The mean (SD) SVC flow was 70.36(39.5) mLs/kg/min. The correlation coefficient of cerebral tissue oxygenation and SVC flow was r = 0.53, p-value 0.005. There was a poor correlation between right and left ventricular output and cTOI which is not surprising considering the influence of intra- and extracardiac shunts. There is a positive relationship between cerebral TOI values and SVC flow in the very low birth infant on day one of life. | 18,945,276 |
Clinical manifestations of infants with nutritional vitamin B deficiency due to maternal dietary deficiency. | In developing countries, nutritional vitamin B(12) deficiency in infants due to maternal diet without adequate protein of animal origin has some characteristic clinical features. In this study, haematological, neurological and gastrointestinal characteristics of nutritional vitamin B(12) deficiency are presented. Hospital records of 27 infants diagnosed in a paediatric haematology unit between 2000 and 2008 were evaluated retrospectively. The median age at diagnosis was 10.5 months (3-24 months). All the infants were exclusively breast fed and they presented with severe nonspecific manifestations, such as weakness, failure to thrive, refusal to wean, vomiting, developmental delay, irritability and tremor in addition to megaloblastic anaemia. The diagnosis was confirmed by complete blood counts, blood and marrow smears and serum vitamin B(12) and folic acid levels. The median haemoglobin level was 6.4 g/dL (3.1-10.6) and mean corpuscular volume (MCV) was 96.8 fL (73-112.3). Some patients also had thrombocytopaenia and neutropaenia. All the infants showed clinical and haematological improvement with vitamin B(12) administration. Patients with severe anaemia causing heart failure received packed red blood cell transfusions as the initial therapy. Paediatricians must consider nutritional vitamin B(12) deficiency due to maternal dietary deficiency in the differential diagnosis of some gastrointestinal, haematological, developmental and neurological disorders of infants with poor socioeconomic status. Delay in diagnosis may cause irreversible neurological damage. | 18,945,280 |
Alcohol-based hand-disinfection reduced children's absence from Swedish day care centers. | To determine if the use of alcohol-based hand-disinfection as a complement to regular hand washing at daycare centers (DCCs) can reduce the childhood rate of absenteeism. Children aged 0-6 years attending DCC were studied in a cluster randomized controlled trial during 30 weeks. Thirty matched pairs of DCCs were included in the study, where one of the DCCs was randomized to intervention and the other to control within each pair. The intervention consisted in children and staff using alcohol-based oily disinfectant gel containing 70% ethanol after regular hand washing. The main outcome was the rate of episodes of absence from DCC due to infection. A regression model was fitted at the individual level and controlling several possible confounders for illness. Absences were reported by the parents. Differences in missing absence reports between the two groups led to only evaluating those 29 DCCs (1431 children) that were able to provide complete reports. In the multivariate regression, the intervention significantly reduced the rate of absenteeism of a child by 12% compared to a child in a control DCC (IRR 95% CI: 0.799-0.965). Hand-disinfection used by children and staff significantly decreased childrens absences due to infections in Swedish DCCs. | 18,945,282 |
Occupational carprofen photoallergic contact dermatitis. | The nonsteroidal anti-inflammatory drug carprofen was used in humans in the 1980s, before its withdrawal due to adverse effects. It re-emerged for veterinary uses, for which it is still widely prescribed, in the 1990s. There has been one previous report published of photoallergic contact dermatitis (PACD) in a pharmaceutical factory worker exposed to carprofen. Investigation of carprofen as a cause of PACD in pharmaceutical factory workers presenting with facial dermatitis. Photopatch testing to carprofen dilutions in two pharmaceutical factory workers and three healthy volunteer controls using the European consensus methodology. This was followed by testing of eight further employees, referred by occupational health services, in the same factory. The index patient suspected a problem with carprofen and was found to have PACD to carprofen. The second patient presented with a widespread, although especially photoexposed site, dermatitis and was initially labelled as having an 'unclassified dermatitis'. Only subsequently was her exposure (indirect; she did not work in the packaging section of the factory like the first patient) to carprofen recognized and testing confirmed both contact allergy and PACD to carprofen. One of three healthy volunteer controls had an active photoallergy sensitization event to carprofen starting 10 days after photopatch testing. Three of eight factory employees subsequently referred because of skin problems had carprofen PACD. Carprofen is a potent photoallergen. These cases emphasize the importance of photopatch testing, and considering agents not included in standard series, when investigating patients presenting with a photoexposed site dermatitis. | 18,945,311 |
Step-wedge cluster-randomised community-based trials: an application to the study of the impact of community health insurance. | We describe a step-wedge cluster-randomised community-based trial which has been conducted since 2003 to accompany the implementation of a community health insurance (CHI) scheme in West Africa. The trial aims at overcoming the paucity of evidence-based information on the impact of CHI. Impact is defined in terms of changes in health service utilisation and household protection against the cost of illness. Our exclusive focus on the description and discussion of the methods is justified by the fact that the study relies on a methodology previously applied in the field of disease control, but never in the field of health financing. First, we clarify how clusters were defined both in respect of statistical considerations and of local geographical and socio-cultural concerns. Second, we illustrate how households within clusters were sampled. Third, we expound the data collection process and the survey instruments. Finally, we outline the statistical tools to be applied to estimate the impact of CHI. We discuss all design choices both in relation to methodological considerations and to specific ethical and organisational concerns faced in the field. On the basis of the appraisal of our experience, we postulate that conducting relatively sophisticated trials (such as our step-wedge cluster-randomised community-based trial) aimed at generating sound public health evidence, is both feasible and valuable also in low income settings. Our work shows that if accurately designed in conjunction with local health authorities, such trials have the potential to generate sound scientific evidence and do not hinder, but at times even facilitate, the implementation of complex health interventions such as CHI. | 18,945,332 |
Open source GIS for HIV/AIDS management. | Reliable access to basic services can improve a community's resilience to HIV/AIDS. Accordingly, work is being done to upgrade the physical infrastructure in affected areas, often employing a strategy of decentralised service provision. Spatial characteristics are one of the major determinants in implementing services, even in the smaller municipal areas, and good quality spatial information is needed to inform decision making processes. However, limited funds, technical infrastructure and human resource capacity result in little or no access to spatial information for crucial infrastructure development decisions at local level.This research investigated whether it would be possible to develop a GIS for basic infrastructure planning and management at local level. Given the resource constraints of the local government context, particularly in small municipalities, it was decided that open source software should be used for the prototype system. The design and development of a prototype system illustrated that it is possible to develop an open source GIS system that can be used within the context of local information management. Usability tests show a high degree of usability for the system, which is important considering the heavy workload and high staff turnover that characterises local government in South Africa. Local infrastructure management stakeholders interviewed in a case study of a South African municipality see the potential for the use of GIS as a communication tool and are generally positive about the use of GIS for these purposes. They note security issues that may arise through the sharing of information, lack of skills and resource constraints as the major barriers to adoption. The case study shows that spatial information is an identified need at local level. Open source GIS software can be used to develop a system to provide local-level stakeholders with spatial information. However, the suitability of the technology is only a part of the system - there are wider information and management issues which need to be addressed before the implementation of a local-level GIS for infrastructure management can be successful. | 18,945,338 |
Oral health status and treatment needs of children and young adults attending a day centre for individuals with special health care needs. | The oral health condition of individuals with special health care needs have been reported in literature to be influenced by various sociodemographic factors, including living conditions and severity of impairment. This study was carried out to determine the oral health status and treatment needs of children and young adults attending a day institution for those with special needs. This study was carried out as part of an oral health screening program organized by the institution and consent was obtained from parents and guardians before the screening. All information was supplied by the parents during the screening using a questionnaire completed by the dentist. Oral examination was carried out on all consenting subjects in attendance on the days of screening in the school clinic with parents and teachers in attendance, using standard World Health Organisation oral health indices to assess dental caries, oral hygiene status, malocclusion and other oral health parameters. Fifty-four subjects aged 3-26 years (mean 12.28 +/- 6.82 years) and comprising 72.2% males and 27.8% females participated in the study. Over 90% were from parents of high and middle level educational background. Thirty-six (66.7%) were caries free, with a mean dmft score of 0.7 +/- 1.77 and mean DMFT score of 0.4 +/- 1.44 with no significant difference across gender (p = 0.5) and parents' educational status (p = 0.43). The mean OHI-S of the total population in this study was 1.36 +/- 0.16. Females had a mean score of 0.88 +/- 1.10 while males had a mean score of 1.55 +/- 1.24 with no significant difference (p = 0.6). Twenty-five (46.3%) had good oral hygiene, 17 (31.5%) had fair oral hygiene and 12 (22.2%) had poor oral hygiene, with no significant difference across gender (p = 1.11) and age groups (p = 0.07). Fifteen (27.8%) had gingivitis with no significant difference across age groups (p = 0.17). Forty-five (83.3%) had Angle's class I malocclusion, 6(11.1%) class II and 3 (5.6%) class III. Chronologic enamel hypoplasia was found in 9 (16.7%) of the total population. Up to 53.7% of the total population will require oral prophylaxis, 33.3% required restorations on their posterior teeth and 12.9% required veneers for labial facing of hypoplastic enamel. The subjects in this study had a high prevalence of dental caries and need for restorative care. They would benefit from parental education on diet modification, improvement of oral hygiene practices and regular dental visits. | 18,945,371 |
Combination antifungal therapy: from bench to bedside. | Invasive fungal infections are major causes of mortality in immunocompromised patients. Despite improved outcomes with new antifungals, there remains a pressing need to further improve outcomes, especially with invasive aspergillosis and other invasive mold infections. Combination antifungal therapy is an attractive option that offers the prospect for improved efficacy, decreased toxicity, reduced likelihood for the emergence of resistance, and shorter courses of therapy. The current available evidence regarding the role of combination antifungal therapy for invasive fungal infections is discussed in this article, including data from in vitro studies, animal models, and human clinical trials to try to clarify this important issue. Randomized, prospective clinical trials are urgently needed, especially for invasive aspergillosis. | 18,945,387 |
Are psychological and pharmacologic interventions equally effective in the treatment of adult depressive disorders? A meta-analysis of comparative studies. | A large number of studies suggest that both psychological and pharmacologic therapies are effective in the treatment of mild-to-moderate depressive disorders. Whether both types of intervention are equally effective has not been established definitively. A database was developed through a comprehensive literature search (from 1966 to May 2007) in which 6947 abstracts in PubMed (1244 abstracts), PsycINFO (1736), EMBASE (1911), and the Cochrane Central Register of Controlled Trials (2056) were examined. Abstracts were identified by combining terms indicative of psychological treatment and depression (both MeSH terms and text words). For this database, the primary studies from 22 meta-analyses of psychological treatment for depression were also collected. For the current study, the abstracts of 832 studies were examined. Thirty randomized trials were included in a meta-analysis that compared the effects of a psychological treatment for 3178 adults with a diagnosed depressive disorder (major depressive disorder, dysthymia, minor depressive disorder) with the effects of a pharmacologic treatment. In studies of patients with dysthymia, pharmacotherapy was significantly more effective than psychotherapy (d = -0.28, 95% CI = -0.47 to -0.10). In patients with major depressive disorder, treatments with selective serotonin reuptake inhibitors (SSRIs) were significantly more effective than psychological treatments, while treatment with other antidepressants did not differ significantly. Subgroup and metaregression analyses did not show that pretest severity of depressive symptoms was associated with differential effects of psychological and pharmacologic treatments of major depressive disorder. Dropout rates were smaller in psychological interventions compared with pharmacologic treatments (odds ratio = 0.66, 95% CI = 0.47 to 0.92). Pharmacologic treatments may be more effective than psychological interventions in the treatment of dysthymia. Pharmacologic treatment with SSRIs may also be more effective in the treatment of major depressive disorder, although these differences are small and probably have little meaning from a clinical point of view. We can conclude that both psychological and pharmacologic therapies are effective in the treatment of depressive disorders and that each has its own merits. | 18,945,396 |
Burden and trends of type-specific human papillomavirus infections and related diseases in the latin america and Caribbean region. | We present the burden of human papillomavirus (HPV)-related cancers (cancers of the cervix, anogenital region, oral cavity and pharynx) in terms of incidence and mortality, for the countries of the Latin America and Caribbean region. The region is a high-risk area for cancer of the cervix and, although incidence has declined since the 1960s, projected demographic changes imply that the actual burden of new cases will increase by more than 75% in the next 20 years, while the average and at diagnosis will increase. Approximately 65% of cervical cancer cases and 50% of the high risk lesions are associated with HPV-16 and 18. Incidence rates of other HPV-related cancers are significantly lower. The paper also describes the estimated impact of genital warts and the limited data available on the occurrence of HPV infections of the upper aerodigestive tract in the region. | 18,945,399 |
New approaches to cervical cancer screening in Latin America and the Caribbean. | Cervical cancer remains an important public health problem in the Latin America and Caribbean region (LAC), with an expected significant increase in disease burden in the next decades as a result of population ageing. Prophylactic human papillomavirus (HPV) vaccine is currently unaffordable in LAC countries. However, even if vaccination was implemented, an additional two decades will be required to observe its impact on HPV related disease and cancer. With some exceptions, cytology-based screening programs have been largely ineffective to control the problem in the region, and there is a need for new approaches to the organization of screening and for use of newly developed techniques. Several research groups in LAC have conducted research on new screening methods, some of which are summarized in this paper. A recommendation to reorganize screening programs is presented considering visual inspection for very low resource areas, improvement of cytology where it is operating successfully and HPV DNA testing followed by visual inspection with acetic acid (VIA) or cytology as soon as this method becomes technically and economically sustainable. This could be facilitated by the incorporation of new, low-cost HPV DNA testing methods and the use of self-collected vaginal specimens for selected groups of the population. An important requisite for screening based on HPV testing will be the quality assurance of the laboratory and the technique by validation and certification measures. | 18,945,402 |
Recommendations for cervical cancer prevention in Latin America and the Caribbean. | Cervical cancer control in the Latin America and Caribbean (LAC) region has been, and remains, a priority and a major public health challenge. It also provides the opportunity for the advancement of research into novel cervical cancer preventative tools including the use of prophylactic human papillomavirus (HPV) vaccines, HPV-based screening options and low technology visual inspection methods. The challenges for prevention are compounded because cervical cancer cases continue to cluster in the low socio-economic and rural populations, thus requiring strong political and social commitments to ensure effective implementation in the region. Although cytology-based screening activities exist in the majority of LAC countries, these have been largely based on opportunistic screening services. Evaluation of the impact of screening is often focused on assessing coverage of the population with Pap smears. However, regardless of the chosen technology a screening program requires a complex set of activities that must also be of high quality such us ensuring access of the underserved populations to the program, maintaining routine quality controls of the screening procedures and organizing the proper follow-up of women with abnormal screening results. The cost of the HPV vaccine and of the delivery infrastructure required is currently a significant obstacle for widespread introduction that will require collaborative resolve between public health organizations, governments and vaccine manufacturers. It is important to ensure that HPV vaccines are made available to the wider public, not only to those who can afford it. This monograph and the associated regional reports have carefully identified and discussed the many challenges and opportunities to be considered for policy decisions, in particular the complex interplay between vaccination strategies and subsequent screening requirements. An advanced cost-benefit analysis, using models calibrated to specific countries in the region, presents the range of options and relative costs thus providing evidence-based scientific guidance to governments and providers in the context of a significant and systematic international review effort. | 18,945,407 |
Silver nanoparticles: green synthesis and their antimicrobial activities. | This review presents an overview of silver nanoparticles (Ag NPs) preparation by green synthesis approaches that have advantages over conventional methods involving chemical agents associated with environmental toxicity. Green synthetic methods include mixed-valence polyoxometallates, polysaccharide, Tollens, irradiation, and biological. The mixed-valence polyoxometallates method was carried out in water, an environmentally-friendly solvent. Solutions of AgNO(3) containing glucose and starch in water gave starch-protected Ag NPs, which could be integrated into medical applications. Tollens process involves the reduction of Ag(NH(3))(2)(+) by saccharides forming Ag NP films with particle sizes from 50-200 nm, Ag hydrosols with particles in the order of 20-50 nm, and Ag colloid particles of different shapes. The reduction of Ag(NH(3))(2)(+) by HTAB (n-hexadecyltrimethylammonium bromide) gave Ag NPs of different morphologies: cubes, triangles, wires, and aligned wires. Ag NPs synthesis by irradiation of Ag(+) ions does not involve a reducing agent and is an appealing procedure. Eco-friendly bio-organisms in plant extracts contain proteins, which act as both reducing and capping agents forming stable and shape-controlled Ag NPs. The synthetic procedures of polymer-Ag and TiO(2)-Ag NPs are also given. Both Ag NPs and Ag NPs modified by surfactants or polymers showed high antimicrobial activity against gram-positive and gram-negative bacteria. The mechanism of the Ag NP bactericidal activity is discussed in terms of Ag NP interaction with the cell membranes of bacteria. Silver-containing filters are shown to have antibacterial properties in water and air purification. Finally, human and environmental implications of Ag NPs to the ecology of aquatic environment are briefly discussed. | 18,945,421 |
Development of a scrotal vasocutaneous fistula producing viable spermatozoa 9 years after vasectomy. | To describe a case of scrotal vasocutaneous fistula discharging viable sperm. Case report. A hospital-based assisted conception center. A 37-year-old male presenting for fertility treatment 9 years after vasectomy with a scrotal vasocutaneous fistula that caused a painful, intermittently rupturing, subcutaneous cyst. Analysis of fistula discharge and planned fistula resection with vasovasostomy. Diagnostic semen analysis to determine presence or absence of spermatozoa in fistula discharge. A very low concentration of live spermatozoa were identified in the fistula discharge. We believe this is the first time that live spermatozoa, potentially suitable for assisted conception treatment using intracytoplasmic sperm injection have been identified in the discharge from a vasocutaneous fistula. | 18,945,427 |
Polydopamine-based permanent coating capillary electrochromatography for auxin determination. | A novel, simple, and economical method for the preparation of open-tubular capillary column using polydopamine coating was reported for the first time. After the capillary was filled with dopamine solution for 20h, polydopamine was formed and deposited on the inner wall of capillary as permanent coating via the oxidation of dopamine by the oxygen dissolved in the solution. Moreover, the electroosmotic flow of the coated capillaries was measured to be dependent on the repetitive coating times. The performance of the polydopamine-coated capillary electrochromatography was validated by the analysis of four auxins, indole-3-butyric acid (IBA), 2,4-dichlorophenoxyacetic acid (dCPAA), indole-3-acetic acid (IAA), and phenoxyacetic acid (PAA). The precisions (RSD, n=5) were in the range of 1.6-2.4% for migration time, 4.0-6.5% for peak area response, and 3.6-4.7% for peak height response for the four auxins at 1microgmL(-1) level. The detection limits were 0.185, 0.172, 0.177, and 0.259microg/mL for IBA, dCPAA, IAA, and PAA, respectively. The method was successfully used to the determination of IAA in the culture media of IAA-producing bacteria. | 18,945,432 |
Upregulation of water channel aquaporin-4 in experimental autoimmune encephalomyeritis. | Aquaporin-4 (AQP4) is a water channel protein that plays an important role in water movement in the central nervous system (CNS). Recently, presence of anti-AQP4 antibody has been reported in the sera from patients with neuromyelitis optica. AQP4 is therefore a possible target for inflammatory mechanisms in CNS. In the present investigation, we performed semi-quantitative analysis of AQP4-mRNA in brain and spinal cord from mice affected with experimental autoimmune encephalomyelitis (EAE) using real-time PCR. AQP4-mRNA expression was increased in EAE; reaching a peak in the spinal cord at 14 days, and in the brain at 21 days after first inoculation. Immunohistochemical analysis showed that AQP4 is expressed on astrocytes, indicating that the increase in AQP4 expression may correlate with astrocytic activation. This is the first study to demonstrate upregulation of AQP4 in EAE. The upregulation of AQP4 could be involved in the development of inflammation in the acute phase of EAE. | 18,945,445 |
Relationship of apoE polymorphism with lipoprotein(a), apoA, apoB and lipid levels in atherosclerotic infarct. | Apolipoprotein E (apoE) polymorphism is suggested to be a risk factor in stroke in some populations, either by affecting lipid parameters or independently. Its effect on lipoprotein(a) [Lp(a)] is not known. The roles of apoE polymorphism and of high Lp(a) levels in atherosclerotic stroke (AS) in the Turkish population are unclear. Our aim was to investigate the relationship of apoE alleles and Lp(a) level with AS and the relationship of apoE alleles with Lp(a) and other lipid parameters. ApoE polymorphisms and lipid parameters were prospectively evaluated in 85 patients and 77 controls with normal brain imaging. Only hypertension, diabetes mellitus, associated vascular diseases and decreased high-density lipoprotein cholesterol levels were found to be independent risk factors for stroke. However, in the presence of apoE/E4 allele, increased low-density lipoprotein cholesterol (LDL-chol), apolipoprotein B (apoB) and Lp(a) levels and in the presence of apo E/E3 allele, only Lp(a) levels were determined as risk factors. This study showed that while apoE polymorphism was not a risk factor itself, high Lp(a), LDL-chol and apoB were determined to be risk factors in E3 or E4 carriers. | 18,945,448 |
Artistic creativity and DBS: a case report. | Deep brain stimulation (DBS) is a treatment for patients with Parkinson's disease (PD) who are not adequately controlled with medications. An artist reported changes in her artistic creativity and art appreciation when treated with left DBS. We sought to study her artistic productions and her appreciation of art while both "on" and "off" left DBS. A 69-year-old right-handed woman with an approximate 20-year history of PD was referred to us for management of a left subthalamic region nucleus (STN) DBS placed at another institution 4 years prior. In Experiment 1 we had her rate several dimensions (Evocative Impact, Aesthetics, Novelty, Technique, Closure and Representation) of another artist's paintings. In Experiment 2, we tested her with the Abbreviated Torrance Test (of creativity) for Adults (ATTA). During testing the patient remained on her dopaminergic medication, but was tested on and off left DBS. On the judgment task while "on" left DBS, versus "off" DBS, there were significant reductions in her appreciation of artistic Closure and Technique. When "off" DBS her ATTA creativity index was above average, but when switched "on" her creativity index was below average. These results suggest the possibility that left ventral STN/SNR DBS reduces creativity as well as appreciation of art. The reason for these alterations is not known, but might be related to enhanced activation of the left hemisphere and reciprocal deactivation of the right hemisphere which mediates both visuospatial skills and global attention, both of which are important in artistic creativity and appreciation. | 18,945,449 |
Quantitative analysis of methanogenic community dynamics in three anaerobic batch digesters treating different wastewaters. | Quantitative changes in methanogenic community structures, associated with performance data, were investigated in three anaerobic batch digesters treating synthetic glucose medium, whey permeate, and liquefied sewage sludge. All digesters were initially seeded with anaerobic sludge obtained from a local municipal wastewater treatment plant. Dynamics of methanogenic populations were monitored, at order and family levels, using real-time PCR based on the 16S rRNA gene. The molecular monitoring revealed that, in each digester, the quantitative structure of methanogenic community varied continuously over treatment time and the variation corresponded well to the changes in chemical profiles. Biphasic production of methane, associated with successive increases in aceticlastic (mainly Methanosarcinaceae) and hydrogenotrophic (mainly Methanomicrobiales) methanogenic groups, was observed in each digester. This corresponded to the diauxic utilization of acetate and longer-chain volatile fatty acids (C(3)-C(6)), mainly propionate. Additionally, the non-metric multidimensional scaling (NMDS) analysis of the quantification results demonstrated that the community shift patterns in three digesters were totally different from each other. Considering that the operating conditions in all trials were identical except substrates, the differences in quantitative shift profiles were suggested to be due to the different substrate compositions. This implied that the composition of wastewater could affect the evolution of quantitative methanogenic community structure in an anaerobic process. Overall, our results suggested that more attention to quantitative as well as qualitative approaches on microbial communities is needed for fundamental understanding of anaerobic processes, particularly under dynamic or transitional conditions. | 18,945,471 |
Design and application of a stratified sampling strategy to study the regional distribution of cyanobacteria (Ile-de-France, France). | This study describes the design and application of a stratified sampling strategy of waterbodies to assess and analyze the distribution of cyanobacteria at a regional scale (Ile-de-France, IDF). Ten groups of hydrographical zones were defined within the IDF on the basis of their anthropogenic and geomorphologic characteristics. Sampling effort (n=50) was then randomly allocated according to the number of waterbodies in each group. This sampling strategy was tested in August 2006, using a field probe to estimate total phytoplankton as well as cyanobacteria biomasses. The sampled waterbodies exhibited a wide range of phytoplankton (< 1-375 microg equiv.Chla L(-1)) and cyanobacteria biomasses (< 1-278 microg equiv.ChlaL(-1)). 72% of the waterbodies in the IDF were classified as eutrophic (42% hypereutrophic), and 24% of the sites studied were dominated by cyanobacteria. Waterbodies connected to hydrographical networks (n=26) showed significantly higher total (p<0.0001; 3.5 times greater) and cyanobacterial (p<0.001, 3.2 times greater) biomasses than the isolated ones (n=24). No significant overall relationship was found through contingency analysis between waterbody trophic status and global land use categories (urban, periurban, and rural) within their hydrographical zones. However, concerning the waterbodies linked to hydrographical networks, the percentage of land covered by forest appeared as a good indicator of phytoplankton and cyanobacterial biomasses. This observation may be a consequence of lower amounts of nutrients being discharged into waterbodies from highly forested hydrological zone than from urban and/or agricultural areas. Our results illustrate a successful means of selecting representative waterbodies to conduct a regional assessment of cyanobacteria distribution using accessible GIS analyses. | 18,945,472 |
Enhanced phytoextraction of an agricultural Cr- and Pb-contaminated soil by bioaugmentation with siderophore-producing bacteria. | Bioaugmentation-assisted phytoextraction may enhance the phytoextraction efficiency thanks to larger metal mobilization by microbial metabolites. Green fluorescent protein-tagged cells of Pseudomonas aeruginosa, Pseudomonas fluorescens or Ralstonia metallidurans, able to produce siderophores, were inoculated in an agricultural soil containing Cr (488 mg kg(-1)) and Pb (382 mg kg(-1)) and maize was cultivated. Bacteria were inoculated as free or immobilized cells in Ca-alginate beads, with skim milk in the aim at improving both the bacterial survival and the in situ siderophore production. Skim milk addition increased inoculated Pseudomonads concentration in soil. Soil inoculation with free cells of R. metallidurans supplied with skim milk increased Cr accumulation in maize shoots by a factor of 5.2 and inoculation with immobilized P. aeruginosa cells supplied with skim milk increased Cr and Pb uptake by maize shoots by a factor of 5.4 and 3.8, respectively. However total metal taken up by the whole plant decreases almost always with bioaugmentation. Translocation factor also increased with P. aeruginosa or R. metallidurans by a factor of 6 up to 7. Inoculated bacteria concentration in soil was correlated with metals in the exchangeable fraction. Cr and Pb concentrations in the exchangeable fraction were correlated with metal contents in shoots or roots. Our results suggest that bioaugmentation-assisted phytoextraction is a relevant method in the aim at increasing the phytoextraction rate which usually limits the use of phytoremediation technologies. | 18,945,474 |
Functional properties of DOM in a stream draining blanket peat. | The functional properties of dissolved organic matter (DOM) from Rough Sike, a stream draining blanket peat in the northern Pennines, UK, were investigated using a series of 12 standardised assays. Nine stream samples were collected at different discharges during 2003--2006, and DOM concentrates obtained by low temperature rotary evaporation. Suwannee River Fulvic Acid was used as a quality control standard in the assays. Dissolved organic matter in high-discharge samples was more light-absorbing at 280 and 340 nm and adsorbed more strongly to alumina, than DOM characteristic of low streamflow, but was less fluorescent and hydrophilic, and poorer in proton-dissociating groups. No significant differences were found in light absorption at 254 nm, copper- or benzo(a)pyrene binding, or photochemical fading. Combination of the Rough Sike data with previously-published results for other streams and a lake yields totals of 20-23 values per assay, for a range of DOM types. For the combined data, variability in all the assays is significant (p < 0.001), as judged by comparison with variations in repeat measurements on the quality control standard. Analysis of the combined data shows that DOM hydrophilicity and adsorption are well-predicted by linear relationships with the extinction coefficient at 340 nm (E340), while good quadratic relationships exist between E340 and both buffering capacity and fluorescence. | 18,945,476 |
Chronic diseases and labour force participation in Australia. | We examine the impact of several chronic diseases on the probability of labour force participation using data from the Australian National Health Surveys. An endogenous multivariate probit model is used to account for the potential endogeneity of the incidence of chronic conditions such as diabetes, cardiovascular diseases and mental illnesses. The cross-equation correlations are significant, rejecting the exogeneity of the chronic illnesses. Marginal effects of exogenous socio-demographic and lifestyle variables are estimated through their direct effects on labour market participation and indirect effects via the chronic diseases. The treatment effects of chronic diseases on labour force participation are estimated via conditional probabilities using five-dimensional normal distributions. The estimated effects differ by gender and age groups. Although computationally more demanding, these treatment effects are compared with results from a univariate model treating the chronic conditions exogenous and the structural effects from the multivariate probit model; both significantly overestimate the effects. | 18,945,504 |
The influence of knowledge, perceptions, and beliefs, on hand hygiene practices in nursing homes. | There are few studies that have assessed factors influencing infection control practices among health care workers (HCW) in nursing homes. We conducted a cross-sectional survey of HCWs (N = 392) in 4 nursing homes to assess whether knowledge, beliefs, and perceptions influence reported hand hygiene habits. Positive perceptions and beliefs regarding effectiveness of infection control in nursing homes were associated with reported appropriate glove use and fingernail characteristics, respectively, among HCWs. Further research on hand hygiene interventions, including targeted educational in-services should be conducted in the nursing home setting. | 18,945,512 |
Mathematical modeling of hepatitis C virus transmission in hemodialysis. | A deterministic mathematical model is developed to explain nontransfusion nosocomial transmission of hepatitis C virus (HCV) from patient to patient during hemodialysis sessions. The model requires 4 sequential steps for cross-transmission: (1) The dialysis session contains at least 1 patient infected with HCV; (2) a hemodialysis staff member connects an uninfected patient to dialysis after having connected an infected patient; (3) the hemodialysis staff member does not change gloves between an infected patient and an uninfected patient; and (4) the uninfected patient is contaminated after exposure to the blood of an infected patient. We tested the model by comparing observed incidences of HCV infection from epidemiologic studies with calculated incidences. Calculated incidences are closed to observed incidences. We assessed the impact of prevalence of HCV infection, no glove change between patients, and nurse:patient ratio on the incidence of HCV infection. We found linear relationships between incidence and prevalence and between incidence and no glove change, and an increasing logarithmic relationship between incidence and nurse:patient ratio. Our model should be able to estimate the likely incidence of infection in hemodialysis centers. Compliance with recommended hand hygiene and glove use practices, especially glove changes between patients, is essential to prevent HCV infection in hemodialysis centers, particularly those with high HCV prevalence. Mathematical modeling can used as a tool for control. | 18,945,513 |
The role of colonization pressure in nosocomial transmission of methicillin-resistant Staphylococcus aureus. | Colonized or infected patients are a major reservoir for patient-to-patient transmission of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals. Despite attempted adherence to recommended infection prevention and control procedures, a general medicine unit in our hospital continued to experience ongoing transmission of MRSA. The role that colonization pressure (CP) plays in nosocomial transmission of MRSA on a general medicine unit was assessed, and a threshold CP above which additional IP&C practices should be implemented was proposed. From January 2005 to December 2006, all patients admitted to a 36-bed general medicine unit were screened on admission for MRSA. Monthly MRSA nosocomial incidence (new nosocomial cases x 1000/susceptible patient-days) and CP (number of MRSA patient-days x 100/total patient-days) were calculated. The relative risk (RR) of MRSA transmission above and below the median CP with 95% confidence interval was calculated. Twenty-one cases of nosocomially acquired MRSA were detected during the study period, with transmission occurring in 8 separate months. The median CP during the 2 years was 6.7%. The RR of MRSA acquisition increased as CP increased above the median (RR, 7.6; 95% CI: 1.1-52.6; P = .008). MRSA outbreaks were declared on 2 separate occasions, and, in each, the CP for the preceding month was greater than the median value of 6.7%. CP has a significant effect on the subsequent transmission of MRSA on a general medicine unit. Ongoing monitoring of CP provides the opportunity for early implementation of enhanced infection prevention and control practices and can potentially decrease nosocomial transmission of MRSA and prevent outbreaks. | 18,945,520 |
A comparative study on the uptake of polycyclic aromatic hydrocarbons by Anodonta californiensis. | Uptake of polycyclic aromatic hydrocarbons (PAHs) by the freshwater bivalve mollusc Anodonta californiensis was examined in the presence and absence of surfactant in order to gain further insight into mixture toxicity and to predict whether certain mixtures have negative and/or positive effects on aquatic organisms. In the presence of surfactant, the uptake of anthracene or chrysene was higher than that of naphthalene, given the same concentration in the solution. In the absence of surfactant, the trend was similar, but the uptakes were increased by approximately 100% compared to those in the presence of surfactant. On the uptake of naphthalene, the presence of anthracene showed only minor influence. The uptake of anthracene was affected by both naphthalene and chrysene. The uptake of chrysene was influenced by neither naphthalene nor anthracene. There was no observable displacement of divalent cations from the surface of the gill membrane by any of the PAHs studied. | 18,945,528 |
General practitioners' experiences and understandings of diagnosing dementia: factors impacting on early diagnosis. | This article reports findings from three linked qualitative research projects that explored how Australian general practitioners (GPs) spoke about their experiences in diagnosing dementia and their views on early diagnosis and barriers towards early diagnosis. The authors conducted this research with the aim of elucidating the GP perspective and using this to better understand the process of diagnosing dementia and delays in diagnosing dementia. Twenty-four GPs based in Australia participated in the study (eleven females and thirteen males). Six of these GPs worked in rural practices, eight in a large town and the remainder in urban practices in a capital city. The major themes in GPs' accounts of the diagnosis of dementia could be grouped under the headings of 'recognizing dementia', 'holistic viewpoint', 'family members and patients' and 'medication'. Key findings are that dementia is a complex condition that takes time to diagnose. Diagnosis may involve conflict between GPs, family members/carers and the person with dementia (PWD). GPs did not consider that diagnosing dementia early was particularly important and may in fact be harmful to some patients. They are skeptical about the advantages of dementia medications. GPs assess the need for a formal diagnosis of dementia within the broader context of their older patients' lives. They are more likely to pursue a formal diagnosis in situations where they see it leading to benefits for their patient such as accessing dementia specific services. Increasing the availability of support services for PWD and educating GPs about the benefits of a formal diagnosis of dementia for stakeholders other than PWD, for example family members and carers may increase the likelihood that they will diagnose dementia early. | 18,945,531 |
Brachiobasilic versus brachiocephalic arteriovenous fistula: a prospective randomized study. | The most recent Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines recommend that the order of preference for arteriovenous fistula (AVF) placement is the radial-cephalic primary AVF, followed by the secondary brachiocephalic (BC) and, if either of these is not viable, then brachiobasilic (BB) AVF should be fashioned. However, there is limited prospective data comparing technical and clinical outcomes of these two approaches. The purpose of our study was to compare outcome, patency, and complication rates in these two autogenous upper arm AV accesses. Between December 2003 and and January 2007, patients (61 male, 39 female) who have lost more distal AVFs were enrolled in the study. After preoperative duplex mapping, patients with patent both basilic and cephalic veins greater than 3 mm of diameter were randomized into BCAVF and BBAVF groups, each group consisting of 50 patients. All procedures were performed under local anesthesia as one-stage procedures. Follow-up data were prospectively collected. Kaplan-Meier analysis was used to calculate primary and secondary patency rates. Univariate and multivariate Cox-regression analysis was used to find risks for the occurrence of thrombosis. Baseline demographics, clinical characteristics, and preoperative history dialysis access were comparable between groups with the exception of the fact that mean caliber of the basilic veins were larger (4.51 +/- 0.93 mm vs 3.90 +/- 0.1 mm; P = .002). The mean duration of operation was significantly shorter in the BC group compared with the BB group (P < .001). There was no significant difference in the thirty day mortality, wound complications, 24 hour thrombosis, postoperative hemorrhage, maturation, and time to maturation between the groups. Mean follow-up was 43.2 +/- 1.8 months. Primary patency at 1 and 3 years of follow-up was 87% and 81% for the BC group and 86% and 73% for the BB group (P = .7) Secondary patency at one and three year follow-up was 87% and 70% for the BC group and 88% and 71% for the BB group, respectively (P = .8). Twenty-eight patients (28%) in the BC (18 patients) and BB (10 patients) group died with a patent fistula during the follow-up period (P = .18). Multivariate analysis revealed that use of dominant arm increased the risk of fistula failure. We conclude that brachiobasilic and brachiocephalic AVF are equally effective alternatives; however, a longer and demanding operation with BB AVF construction should be considered. | 18,945,577 |
Quality of life in patients with lower limb ischemia; revised suggestions for analysis. | Quality of life (QoL) is a crucial outcome measure in patients with lower limb ischemia (LLI). The Short Form 36 (SF36) has been proposed as the gold standard instrument for generic QoL analysis in patients with LLI. The Short Form 8 (SF8) was developed from the SF36 and we aim to compare these two instruments in terms of validity, reliability, and responsiveness. One hundred ninety-three patients, 135 men and 58 women, median age 66 (range, 44-84) years with LLI completed the SF36 and the SF8. Disease severity was graded according to International Society of Cardiovascular Surgery (ISCVS) suggested reporting standards. Correlation between the two instruments' like domains and non-like domains reflects convergent and divergent validity respectively. A subgroup of 58 patients (44 men) completed two sets of questionnaires, with an intervening period of 2 weeks. Correlation between these two sets of questionnaires was used to analyze test/retest reliability. Spearman's rank correlation was used to analyze validity and reliability. Responsiveness of the individual domains across the whole group was analyzed using the Kruskall-Wallis analysis of variance (ANOVA) test, while responsiveness between the groups of patients with varying severity of LLI was analyzed using the Mann-Whitney U test. There was greater correlation between like domains of SF36 and the SF8 than the non-like domains suggesting good convergent-divergent validity. Test/retest reliability was significant for both instruments (r(s) > 0.7). Increasing LLI resulted in a statistically significant deterioration in all eight domains of both instruments. The time taken was significantly shorter and less assistance was required to complete the SF8 than the SF36. The SF8 is a valid and reliable QoL instrument in patients with LLI, and as it is simpler and quicker to complete, we suggest it may challenge the SF36 as the gold standard generic QoL analysis instrument in LLI. | 18,945,581 |
Validity of self-reported sunscreen use by parents, children, and lifeguards. | Verbal self-report is the method most often used to assess sunscreen use, but the data may be confounded by recall error and social desirability. Sunscreen swabbing is a non-invasive procedure to objectively assess the presence of sunscreen on the skin. This study examined the agreement between verbal reports of sunscreen use from survey and diary measures and objectively measured sunscreen use. Participants were 564 parents, children aged 5-10 years, and lifeguards at 16 swimming pools in four regions of the U.S. Participants completed self-reported measures, including baseline and final surveys, as well as a 4-day diary and objective swabbing measures of sunscreen presence on 2 separate days. Data were collected in 2006 and analyzed in 2006-2007. Levels of sunscreen use were relatively high based on surveys (65.7%); diary data (40.3%); and swabbing measures (59.1%). Agreement between swabbing and diary measures of sunscreen use was fair to good, with kappa statistics for children at 0.40, followed by lifeguards at 0.34 and parents at 0.27. Validity coefficients across measures of sunscreen use were higher for lifeguards and parents than for children, and diary measures were higher than surveys. No systematic errors were found across groups or by gender, latitude, study arm, or risk category. These findings are comparable to those in other validation studies, including studies of the validity of dietary assessments. Self-reported estimates of sunscreen use by diaries or surveys appear to be as good as objective measures. | 18,945,582 |
Thicker paper and larger font increased response and completeness in a postal survey. | To investigate the effect of font size and paper thickness on the response to, and completion of, a self-completion postal questionnaire among older people with joint pain. Randomized trial. People aged 50 years and older with joint pain who consulted a general practitioner at one of five general practices in Central Cheshire were sent a postal questionnaire. Questionnaire format (large or small font size, thick or thin paper) was randomly allocated using a 2 x 2 factorial design. Questionnaires were received from 502 out of 650 participants (crude response 77%). Response was significantly higher for participants receiving questionnaires with a larger font size (79.3% vs. 75.2%; hazard ratio 1.26, 95% confidence interval: 1.02, 1.56). Paper thickness had no significant effect on response. Completion (measure by assessing double-page turnover error) was increased in participants receiving questionnaires printed on thicker paper (3.2% vs. 7.1%; P=0.049) but was not affected by font size. This study demonstrates that questionnaires in larger font and on thicker paper may produce higher and more complete responses than surveys using standard size font and standard thickness paper, and should therefore be considered in studies among older people. | 18,945,586 |
Course of illness in a sample of 265 patients with first-episode psychosis--five-year follow-up of the Danish OPUS trial. | There is an ongoing debate as to whether psychosis is a progressively deteriorating illness or one of progressive amelioration. This paper aims at investigating the rate of recovery and institutionalization and predicting a continuous illness course in a descriptive prospective study of a sub-sample of the OPUS trial of 265 first-episode psychotic patients after five years. Recovery, defined as no psychotic or negative symptoms, living independently, GAF (f)>59, working or studying, was reached for 18% after five years, whereas 13% were institutionalized either at hospital or supported housing after five years. Male gender (OR 1.9, 95% CI 1.06 to 3.23), premorbid social functioning (OR 1.2, 95% CI 1.01 to 1.33), psychotic symptoms (OR 1.3, 95% CI 1.07 to 1.66), and negative symptoms (OR 1.3, 95% CI 1.01 to 1.67) were found to predict a continuous illness course at five-year follow-up. Rates of recovery and institutionalization contradict the assumption that the illness deteriorates progressively, since no changes in the rates are seen from two to five years. | 18,945,593 |
Mebudipine and dibudipine protect PC12 cells against oxygen-glucose deprivation and glutamate-induced cell death. | The protective effect of two new L-type calcium-channel blockers, mebudipine and dibudipine on neurotoxic effects induced by glutamate and oxygen-glucose deprivation (OGD) in PC12 cells was investigated. PC12 cells were intoxicated with two different methods. First, the cells were incubated with glutamate (10muM/L), glutamate and mebudipine (10muM/L), dibudipine (10muM/L) or nimodipine (10muM/L), on three different treatment schedules (concurrently, pre-3h and pre-24h). In the second method PC12 cells were exposed to in vitro oxygen-glucose deprivation for 30min and 60min alone or with the drugs in the same time schedules described above. Cellular viability was assessed by MTT assay. Glutamate-induced cell death and OGD-induced cell injury were attenuated significantly by mebudipine, dibudipine in comparison with nimodipine in all three different treatment schedules. Application of MK801 (10muM/L), an antagonist of NMDA glutamate receptors inhibited PC12 cell death in both methods. Our study suggests that mebudipine and dibudipine, like nimodipine, may have protective effects against glutamate and oxygen-glucose deprivation-induced neurotoxicity. | 18,945,602 |
Molecular phylogeny and systematics of Polyblastia (Verrucariaceae, Eurotiomycetes) and allied genera. | Phylogenetic relationships of the lichen genus Polyblastia and closely related taxa in the family Verrucariaceae (Verrucariales, Chaetothyriomycetidae) were studied. A total of 130 sets of sequences (nuLSU rDNA, nuITS rDNA and RPB1 region A-D), including 129 newly generated sequences, were analysed. Phylogenetic relationships were inferred using a Bayesian approach based on two datasets. A first analysis of a larger, two-locus dataset (nuLSU and RPB1) for 128 members of the Verrucariaceae, confirmed the polyphyly of Polyblastia, Thelidium, Staurothele, and Verrucaria, as currently construed. The second analysis focused on 56 Polyblastia and allied taxa, but using an additional locus (nuITS rDNA) and two closely related outgroup taxa. The latter analysis revealed strongly supported groups, such as Polyblastia s. str., the Thelidium group (a mixture of Polyblastia, Thelidium, Staurothele and Verrucaria species). The genus Sporodictyon, which is here accepted, also accommodates Sporodictyon terrestre comb. nov. Morphological features traditionally used for characterizing Polyblastia, Thelidium, Staurothele and Verrucaria, such as spore septation and colour, occurrence of hymenial photobiont, involucrellum structure, and substrate preference, were found to be only partially consistent within the strongly supported clades, and thus are not always reliable features for characterizing natural groups. | 18,945,603 |
Succinyl hydroxamates as potent and selective non-peptidic inhibitors of procollagen C-proteinase: design, synthesis, and evaluation as topically applied, dermal anti-scarring agents. | Succinyl hydroxamates 1 and 2 are disclosed as novel series of potent and selective inhibitors of procollagen C-proteinase (PCP) which may have potential as anti-fibrotic agents. Carboxamide 7 demonstrated good PCP inhibition and had excellent selectivity over MMPs involved in wound healing. In addition, 7 was effective in a cell-based model of collagen deposition (fibroplasia model) and was very effective at penetrating human skin in vitro. Compound 7 (UK-383,367) was selected as a candidate for evaluation in clinical studies as a topically applied, dermal anti-scarring agent. | 18,945,617 |
Creative elements: network-based predictions of active centres in proteins and cellular and social networks. | Active centres and hot spots of proteins have a paramount importance in enzyme action, protein-complex formation and drug design. Recently, several publications successfully applied the analysis of residue networks to predict active centres in proteins. Most real-world networks show several properties, such as small-worldness or scale-free degree distribution, which are rather general features of networks, from molecules to society at large. Using analogy, I propose that existing findings and methodology already enable us to detect active centres in cells and can be expanded to social networks and ecosystems. Members of these active centres are termed here as 'creative elements' of their respective networks, which can help them to survive unprecedented, novel challenges and play a key part in the development, survival and evolvability of complex systems. | 18,945,619 |
Synthesis and antiviral activity of novel pyrazole derivatives containing oxime esters group. | Fourteen title compounds, 1-substituted-5-substitutedphenylthio-4-pyrazolaldoxime ester derivatives 4a-4n, were synthesized from the starting material 1-substitutedphenyl-3-methyl-5-substitutedphenylthio-4-pyrazolaldoximes 3 by treatment with acyl chloride. The synthesized compounds were characterized by physical constants, and the structures of the title compounds were further confirmed by IR, 1H NMR, 13C NMR and elemental analysis. The bioassay results showed that title compounds possessed weak to good anti-TMV bioactivity with 4l showing significant enhancement of disease resistance in tobacco leaves with high affinity for TMV CP. | 18,945,621 |
Low susceptibility of NC/Nga mice to tumor necrosis factor-alpha-mediated lethality and hepatocellular damage with D-galactosamine sensitization. | The susceptibility of NC/Nga mice to tumor necrosis factor (TNF)-alpha was examined by using sensitization with d-galactosamine (d-GalN). Administration of TNF-alpha and d-GalN killed none of the NC/Nga mice, whereas it killed all of the BALB/c mice. Treatment with TNF-alpha and d-GalN caused few hepatic lesions in NC/Nga mice but massive hepatocellular apoptosis in BALB/c mice. Unlike BALB/c mice, there was no elevation in caspase 3 and 8 activities in the livers of NC/Nga mice receiving TNF-alpha and d-GalN. On the other hand, administration of anti-Fas antibody definitely killed both NC/Nga and BALB/c mice via activation of caspases 3 and 8. Treatment with TNF-alpha and d-GalN led to translocation of nuclear factor (NF)-kappaB in NC/Nga and BALB/c mice. However, NF-kappaB translocation was sustained in NC/Nga mice, although it disappeared in BALB/c mice 7 h after the treatment. NF-kappaB inhibitors activated caspases 3 and 8, and enhanced TNF-alpha-mediated lethality in NC/Nga. Taken together, the low susceptibility of NC/Nga mice to TNF-alpha-mediated lethality was suggested to be responsible for the sustained NF-kappaB activation. | 18,945,641 |
Simultaneous determination of doxifluridine and 5-fluorouracil in monkey serum by high performance liquid chromatography with tandem mass spectrometry. | A reverse-phase high performance liquid chromatography method with electrospray ionization and detection by mass spectrometry is described for the simultaneous determination of doxifluridine and its active metabolite 5-fluorouracil in monkey serum. A liquid/liquid extraction with ethyl acetate (90%) and isopropyl alcohol (10%) was used to extract simultaneously doxifluridine and 5-FU which have considerable difference in the polarity. Optimum chromatographic separation was achieved on a Agilent Zorbax C(18) (100 mm x 2.1mm, 3.5 microm) column with a mobile phase of methanol-water (20:80, v/v). The flow rate was 0.2 mL/min with total cycle time of 5 min. The lower limit of quantification (LLOQ) was validated at 10.0 ng/mL of serum for both doxifluridine and 5-FU. Accuracy and precision of quality control (QC) samples for both compounds met FDA Guidance criteria of +/-15% with average QC accuracy of 95.5-105.0% and coefficients of variation of 1.1-9.5% in the 10-2000 ng/mL concentration range. This method demonstrated adequate sensitivity, specificity, accuracy, precision, stability to support the analysis of monkey serum samples. | 18,945,647 |
Determination of metaldehyde in human serum by headspace solid-phase microextraction and gas chromatography-mass spectrometry. | A rapid headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) method has been developed for the determination of metaldehyde in human serum samples. Metaldehyde is extensively used as a molluscicide for the control of slugs and snails, and cases of metaldehyde poisoning have been reported. Metaldehyde was headspace-extracted on a polydimethylsiloxane (PDMS) fiber at 70 degrees C for 25 min, desorbed, and analyzed rapidly by GC-MS. The method was validated for limit of detection (LOD), linearity, precision, and recovery. Although the recovery of the sample was very low, the method itself was rapid with a low detection limit of 0.25 microg/ml, R.S.D. value 12.6%, and linearity range 0.5-25.0 microg/ml (r(2)=0.999). The results demonstrated that the SPME-GC-MS method for the analysis of metaldehyde is simple, rapid, solvent-free, and does not require any pre-analysis conversions. | 18,945,651 |
Management and long-term follow-up of early stage H. pylori-associated gastric MALT-lymphoma in clinical practice: an Italian, multicentre study. | Data on management and long-term follow-up of Helicobacter pylori-associated MALT-lymphoma in clinical practice are scanty. We evaluate the long-term efficacy of H. pylori eradication on low-grade MALT-lymphoma, and the efficacy of further therapies in refractory patients. This study enrolled patients with stages I-II(1) MALT-lymphoma and H. pylori infection. H. pylori eradication was attempted in all patients. Patients with lymphoma persistence or progression following H. pylori treatments received further lymphoma treatments. Both 5-year and disease-free survivals were calculated. Sixty patients (stage I/II(1): 50/10) were followed up for a median time of 65 months (range 7-156). H. pylori infection was successfully eradicated in 53 (88.3%) patients following three consecutive therapeutic attempts, and lymphoma regressed in 42 (79.2%) of these patients. Sixteen patients received anti-neoplastic treatments due to either lymphoma persistence or progression, and lymphoma was cured in 14 (87.5%) cases. At follow-up, lymphoma relapsed in 13/42 (30.9%) patients within a median time of 19 months (range 3-41), and all but 1 patient were cured with further therapies. Overall, lymphoma regression was achieved in 56 patients (93.3%). The 5-year and disease-free survivals were 94.7% and 74.6%, respectively. In clinical practice, a conservative approach with antibiotic eradication seems to be appropriate management for early-stage MALT-lymphoma, with oncologic therapy being reserved for those patients who fail to respond to H. pylori therapy. | 18,945,654 |
Dietary iron intake and risk of Parkinson's disease. | Dietary iron is the most important source of iron stores. Several case-control studies have described the association of high dietary iron and Parkinson's disease, but prospective data are lacking. The authors prospectively followed 47,406 men and 76,947 women from the United States who provided information through a mailed questionnaire on their diet, medical history, and lifestyle practices between 1984 and 2000. The authors documented 422 new cases of Parkinson's disease. Total iron intake was not associated with an increased risk of Parkinson's disease (relative risk (RR) = 1.10, 95% confidence interval (CI): 0.74, 1.65; P(trend) = 0.84), but dietary nonheme iron intake from food was associated with a 30% increased risk of Parkinson's disease (RR = 1.27, 95% CI: 0.92, 1.76; P(trend) = 0.02). A secondary analysis revealed that Parkinson's disease risk was significantly increased among individuals with high nonheme iron and low vitamin C intakes (RR = 1.92, 95% CI: 1.14, 3.32; P(trend) = 0.002). Supplemental iron intake was associated with a borderline increase in Parkinson's disease risk among men. Although the authors' prospective data did not support an association between total iron intake (dietary and supplemental) and risk of Parkinson's disease, a 30% increased risk was associated with a diet rich in nonheme iron. This increase in risk was present in those who had low vitamin C intake. | 18,945,687 |
Formation of nucleoprotein filaments by mammalian DNA methyltransferase Dnmt3a in complex with regulator Dnmt3L. | The C-terminal domains of Dnmt3a and Dnmt3L form elongated heterotetramers (3L-3a-3a-3L). Analytical ultracentrifugation confirmed the Dnmt3a-C/3L-C complex exists as a 2:2 heterotetramer in solution. The 3a-3a interface is the DNA-binding site, while both interfaces are essential for AdoMet binding and catalytic activity. Hairpin bisulfite analysis shows correlated methylation of two CG sites in a distance of approximately 8-10 bp in the opposite DNA strands, which corresponds to the geometry of the two active sites in one Dnmt3a-C/3L-C tetramer. Correlated methylation was also observed for two CG sites at similar distances in the same DNA strand, which can be attributed to the binding of two tetramers next to each other. DNA-binding experiments show that Dnmt3a-C/3L-C complexes multimerize on the DNA. Scanning force microscopy demonstrates filament formation rather than binding of single tetramers and shows that protein-DNA filament formation leads to a 1.5-fold shortening of the DNA length. | 18,945,701 |
Early repolarization phenomenon in arrhythmogenic right ventricular dysplasia-cardiomyopathy and sudden cardiac arrest due to ventricular fibrillation. | The case of a 26-year-old male with sudden cardiac arrest due to ventricular fibrillation and the final diagnosis of arrhythmogenic right ventricular dysplasia-cardiomyopathy (ARVD/C) and initial early repolarization phenomenon is presented in detail. An additional analysis of early repolarization in additional 359 patients with ISFC/ESC diagnostic criteria of ARVD/C revealed a frequency within the threshold in healthy volunteers with 3% in isolated lateral leads and 7% in inferolateral leads. The high frequency of electrocardiographic early repolarization limited to inferior leads (22%) is probably due to late depolarization and represents an already reported typical feature of ARVD/C. | 18,945,711 |
R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study. | The role of re-treatment with rituximab in aggressive B-cell lymphomas still needs to be defined. This study evaluated the influence of prior exposure to rituximab on response rates and survival in patients with diffuse large B-cell lymphoma treated with rituximab plus etoposide, cytarabine, cisplatinum and methylprednisolone (R-ESHAP). We retrospectively analyzed 163 patients with relapsed or refractory diffuse large B-cell lymphoma who received R-ESHAP as salvage therapy with a curative purpose. Patients were divided into two groups according to whether rituximab had been administered (n=94, "R+" group) or not (n=69, "R-" group) prior to R-ESHAP. Response rates were significantly higher in the R- group in the univariate but not in the multivariate analysis. In the analysis restricted to the R+ group, we observed very low complete remission and overall response rates in patients with primary refractory disease (8% and 33%, respectively), as compared to those in patients who were in first partial remission (41% and 86%) or who had relapsed disease (50% and 75%) (p<0.01 in both cases). Overall, 60% and 65% of patients in the R+ and R- groups, respectively, underwent stem-cell transplantation after the salvage therapy. With a median follow-up of 29 months (range, 6-84), patients in the R+ group had significantly worse progression-free survival (17% vs. 57% at 3 years, p<0.0001) and overall survival (38% v 67% at 3 years, p=0.0005) than patients in the R- group. Prior exposure to rituximab was also an independent adverse prognostic factor for both progression-free survival (RR: 2.0; 95% CI: 1.2-3.3, p=0.008) and overall survival (RR: 2.2; 95% CI: 1.3-3.9, p=0.004). R-ESHAP was associated with a high response rate in patients who were not refractory to upfront rituximab-based chemotherapy. However, the survival outcome was poor for patients previously exposed to rituximab, as compared to in those who had not previously been treated with rituximab. | 18,945,747 |
Control of the papillomavirus early-to-late switch by differentially expressed SRp20. | The viral early-to-late switch of papillomavirus infection is tightly linked to keratinocyte differentiation and is mediated in part by alternative mRNA splicing. Here, we report that SRp20, a cellular splicing factor, controls the early-to-late switch via interactions with A/C-rich RNA elements. An A/C-rich SE4 element regulates the selection of a bovine papillomavirus type 1 (BPV-1) late-specific splice site, and binding of SRp20 to SE4 suppresses this selection. Expression of late BPV-1 L1 or human papillomavirus (HPV) L1, the major capsid protein, inversely correlates with SRp20 levels in the terminally differentiated keratinocytes. In HPV type 16, a similar SRp20-interacting element also controls the viral early-to-late switch. Keratinocytes in raft cultures, which support L1 expression, make considerably less SRp20 than keratinocytes in monolayer cultures, which do not support L1 expression. Conversely, abundant SRp20 in cancer cells or undifferentiated keratinocytes is important for the expression of the viral early E6 and E7 by promoting the expression of cellular transcription factor SP1 for transactivation of viral early promoters. | 18,945,760 |
Infection with human cytomegalovirus alters the MMP-9/TIMP-1 balance in human macrophages. | Human cytomegalovirus (HCMV) has been suggested to contribute to the development of vascular diseases. Since matrix metalloproteinases (MMPs) have been implicated in atherosclerosis and plaque rupture, we investigated the effect of HCMV infection on MMP expression in human macrophages. We used quantitative real-time PCR, Western blotting, and gelatin zymography to study the expression and activity of MMP-2, -3, -7, -9, -12, -13, and -14 and of tissue inhibitor of metalloproteinase 1 (TIMP-1), -2, -3, and -4. HCMV infection reduced MMP-9 mRNA, protein, and activity levels but increased TIMP-1 mRNA and protein levels. Furthermore, a decrease in MMP-12, MMP-14, TIMP-2, and TIMP-3 mRNA levels could be detected. The MMP-9 and TIMP-1 mRNA alterations required viral replication. MMP-9 mRNA expression was affected by an immediate-early or early viral gene product, whereas TIMP-1 mRNA expression was affected by late viral gene products. We conclude that HCMV infection specifically alters the MMP-9/TIMP-1 balance in human macrophages, which in turn reduces MMP-9 activity in infected cells. Since MMP-9 prevents atherosclerotic plaque development in mice, these results suggest that HCMV may contribute to atherogenesis through specific effects on MMP-9 activity. | 18,945,772 |
Kaposi's sarcoma-associated herpesvirus gH/gL: glycoprotein export and interaction with cellular receptors. | The attachment, entry, and fusion of Kaposi's sarcoma-associated herpesvirus (KSHV) with target cells are mediated by complex machinery containing, among others, viral glycoprotein H (gH) and its alleged chaperone, gL. We observed that KSHV gH, in contrast to its homologues in several other herpesviruses, is transported to the cytoplasm membrane independently from gL, but not vice versa. Mutational analysis revealed that the N terminus of gH is sufficient for gL interaction. However, the entire extracellular part of gH is required for efficient gL secretion. The soluble ectodomain of gH was sufficient to interact with the surfaces of potential target cells in a heparin-dependent manner, and binding was further enhanced by coexpression of gL. Surface plasmon resonance revealed a remarkably high affinity of gH for glycosaminoglycans. Heparan sulfate (HS) proteoglycans of the syndecan family act as cellular receptors for the gH/gL complex. They promoted KSHV infection, and expression of gH/gL on target cells inhibited subsequent KSHV infection. Whereas gH alone was able to bind to HS, we observed that only the gH/gL complex adhered to heparan sulfate-negative cells at lamellipodium-like structures. | 18,945,775 |
Deletion of the first cysteine-rich region of the varicella-zoster virus glycoprotein E ectodomain abolishes the gE and gI interaction and differentially affects cell-cell spread and viral entry. | Varicella-zoster virus (VZV) glycoprotein E (gE) is the most abundant glycoprotein in infected cells and, in contrast to those of other alphaherpesviruses, is essential for viral replication. The gE ectodomain contains a unique N-terminal region required for viral replication, cell-cell spread, and secondary envelopment; this region also binds to the insulin-degrading enzyme (IDE), a proposed VZV receptor. To identify new functional domains of the gE ectodomain, the effect of mutagenesis of the first cysteine-rich region of the gE ectodomain (amino acids 208 to 236) was assessed using VZV cosmids. Deletion of this region was compatible with VZV replication in vitro, but cell-cell spread of the rOka-DeltaCys mutant was reduced significantly. Deletion of the cysteine-rich region abolished the binding of the mutant gE to gI but not to IDE. Preventing gE binding to gI altered the pattern of gE expression at the plasma membrane of infected cells and the posttranslational maturation of gI and its incorporation into viral particles. In contrast, deletion of the first cysteine-rich region did not affect viral entry into human tonsil T cells in vitro or into melanoma cells infected with cell-free VZV. These experiments demonstrate that gE/gI heterodimer formation is essential for efficient cell-cell spread and incorporation of gI into viral particles but that it is dispensable for infectious varicella-zoster virion formation and entry into target cells. Blocking gE binding to gI resulted in severe impairment of VZV infection of human skin xenografts in SCIDhu mice in vivo, documenting the importance of cell fusion mediated by this complex for VZV virulence in skin. | 18,945,783 |
MR imaging characteristics and neuropathology of the spinal cord in adult-onset autosomal dominant leukodystrophy with autonomic symptoms. | MR imaging findings in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms have been described in the brain, but no descriptions of MR imaging findings in the spinal cord have been published. Here, we describe MR imaging findings in the spinal cord in adult-onset ADLD with autonomic symptoms and histopathologic investigations of the spinal cord. Twelve subjects from 2 families with adult-onset ADLD with autonomic symptoms identified by clinical investigation underwent MR imaging examination of the spinal cord. Sagittal and transverse sections were obtained. MR imaging examination of the brain was performed in 11 patients. One of the patients underwent postmortem examination, and the spinal cord was subjected to histopathologic analysis. In all family members with adult-onset ADLD with autonomic symptoms, even in the asymptomatic person, the spinal cord was thin. All examined family members also had a slight general white matter signal intensity (SI) increase in the whole spinal cord, mainly visible in T2-weighted transverse images. The pathologic examination revealed a discrete demyelination in the spinal cord. Brain MR imaging also showed increased T2 SI in the white matter. The spinal cord is affected in adult-onset ADLD with autonomic symptoms. Findings consist of atrophy and a diffuse T2 SI increase in the white matter. Transverse images are needed to assess these findings. The typical SI changes of the spinal cord are also present in subjects without clinical symptoms of the disease and with very limited changes in the brain. | 18,945,794 |
Dilation of the subarachnoid spaces surrounding the cranial nerves with petrous apex cephaloceles in Usher syndrome. | Limited studies of brain MR imaging findings in Usher syndrome have reported atrophy with enlarged subarachnoid spaces. However, the specific appearance of the subarachnoid spaces surrounding the cranial nerves has not yet been described. Herein we describe the skull base MR imaging findings in an adult with Usher syndrome. Multiple cranial nerve exits were enlarged to the point of causing cephaloceles with bony remodeling. A combination of uncommon findings in this rare disorder raises the question of an etiologic association. | 18,945,801 |
Coupling between horizontal and vertical components of saccadic eye movements during constant amplitude and direction gaze shifts in the rhesus monkey. | When the head is free to move, changes in the direction of the line of sight (gaze shifts) can be accomplished using coordinated movements of the eyes and head. During repeated gaze shifts between the same two targets, the amplitudes of the saccadic eye movements and movements of the head vary inversely as a function of the starting positions of the eyes in the orbits. In addition, as head-movement amplitudes and velocities increase, saccade velocities decline. Taken together these observations lead to a reversal in the expected correlation between saccade duration and amplitude: small-amplitude saccades associated with large head movements can have longer durations than larger-amplitude saccades associated with small head movements. The data in this report indicate that this reversal occurs during gaze shifts along the horizontal meridian and also when considering the horizontal component of oblique saccades made when the eyes begin deviated only along the horizontal meridian. Under these conditions, it is possible to determine whether the variability in the duration of the constant amplitude vertical component of oblique saccades is accounted for better by increases in horizontal saccade amplitude or increases in horizontal saccade duration. Results show that vertical saccade duration can be inversely related to horizontal saccade amplitude (or unrelated to it) but that horizontal saccade duration is an excellent predictor of vertical saccade duration. Modifications to existing hypotheses of gaze control are assessed based on these new observations and a mechanism is proposed that can account for these data. | 18,945,817 |
Dynamic metabotropic control of intrinsic firing in cerebellar unipolar brush cells. | Neuronal firing is regulated by the complex interaction of multiple depolarizing and hyperpolarizing currents; intrinsic firing, which defines the neuronal ability to generate action potentials in the absence of synaptic excitation, is particularly sensitive to modulation by currents that are active below the action potential threshold. Cerebellar unipolar brush cells (UBCs) are excitatory granule layer interneurons that are capable of intrinsic firing; here we show that, in acute mouse cerebellar slices, barium-sensitive background potassium channels of UBCs effectively regulate intrinsic firing. We also demonstrate that these channels are regulated by group II metabotropic glutamate receptors (mGluRs), which we show to be present in both of the known subsets of UBCs, one of which expresses calretinin and the other mGluR1alpha. Finally, we show that background potassium currents controlling UBCs' firing are mediated by at least two channel types, one of which is sensitive and the other insensitive to the GIRK blocker tertiapin. Thus in UBCs, glutamatergic transmission appears to have a complex bimodal effect: although it increases spontaneous firing through activation of ionotropic receptors, it also has inhibitory effects through the mGluR-dependent activation of tertiapin-sensitive and -insensitive background potassium currents. | 18,945,818 |
Angiotensin II-induced contraction is attenuated by nitric oxide in afferent arterioles from the nonclipped kidney in 2K1C. | Two-kidney, one-clip (2K1C) is a model of renovascular hypertension where we previously found an exaggerated intracellular calcium (Ca(i)(2+)) response to ANG II in isolated afferent arterioles (AAs) from the clipped kidney (Helle F, Vagnes OB, Iversen BM. Am J Physiol Renal Physiol 291: F140-F147, 2006). To test whether nitric oxide (NO) ameliorates the exaggerated ANG II response in 2K1C, we studied ANG II (10(-7) mol/l)-induced calcium signaling and contractility with or without the NO synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME). In AAs from the nonclipped kidney, l-NAME increased the ANG II-induced Ca(i)(2+) response from 0.28 +/- 0.05 to 0.55 +/- 0.09 (fura 2, 340 nm/380 nm ratio) and increased contraction from 80 +/- 6 to 60 +/- 6% of baseline (P < 0.05). In vessels from sham and clipped kidneys, l-NAME had no effect. In diaminofluorescein-FM diacetate-loaded AAs from the nonclipped kidney, ANG II increased NO-derived fluorescence to 145 +/- 34% of baseline (P < 0.05 vs. sham), but not in vessels from the sham or clipped kidney. Endothelial NOS (eNOS) mRNA and ser-1177 phosphorylation were unchanged in both kidneys from 2K1C, while eNOS protein was reduced in the clipped kidney compared with sham. Cationic amino acid transferase-1 and 2 mRNAs were increased in 2K1C, indicating increased availability of l-arginine for NO synthesis, but counteracted by decreased scavenging of the eNOS inhibitor asymmetric dimethylarginine by dimethylarginine dimethylaminohydrolase 2. In conclusion, the Ca(i)(2+) and contractile responses to ANG II are blunted by NO release in the nonclipped kidney. This may protect the nonclipped kidney from the hypertension and elevated ANG II levels in 2K1C. | 18,945,823 |
Treatment of congenital tuberculosis. | The diagnosis and treatment of congenital tuberculosis are discussed. Congenital tuberculosis is rare and fatal if left untreated. If a pregnant woman with tuberculosis is not treated, infection of the fetus can occur by hematogenous spread through the umbilical cord or by aspiration or ingestion of amniotic fluid. Signs and symptoms of congenital tuberculosis may be nonspecific, which may preclude early diagnosis and treatment. Criteria for the diagnosis of congenital tuberculosis require the infant to have a tuberculous lesion, as indicated by chest radiography or granulomas, and at least one of the following should be confirmed: (1) onset during the first week of life, (2) primary hepatic tuberculosis complex or caseating hepatic granulomas, (3) infection of the placenta or maternal genital tract, or (4) exclusion of postnatal transmission by a contact investigation. Since 2001, 21 cases of congenital tuberculosis have been reported in English-language medical journals, with the age of presentation ranging from day 1 to 90. Based on findings from published case reports, congenital tuberculosis should be considered in the differential diagnosis of newborns who have (1) nonresponsive, worsening pneumonia, especially in regions with high rates of tuberculosis, (2) nonspecific symptoms but have a mother diagnosed with tuberculosis, (3) high lymphocyte counts in the cerebrospinal fluid without an identified bacterial pathogen, or (4) fever and hepatosplenomegaly. Once diagnosed, it is essential to promptly begin treatment with isoniazid, rifampin, pyrazinamide, and streptomycin in order to decrease the mortality associated with the infection. Early diagnosis and treatment during the neonatal period are crucial in minimizing the fatality associated with congenital tuberculosis. | 18,945,861 |
Alkaline ceramidase 2 regulates beta1 integrin maturation and cell adhesion. | The polypeptide core of the integrin beta1 subunit (beta1) is glycosylated sequentially in the endoplasmic reticulum and the Golgi complex to form beta1 precursor and mature beta1, respectively. The beta1 precursor to mature beta1 conversion, termed beta1 maturation, regulates the cell surface levels and function of beta1-containing integrins, beta1 integrins. Here we demonstrate that the human alkaline ceramidase 2 (ACER2), a Golgi enzyme, regulates beta1 maturation by controlling the generation of sphingosine. ACER2 overexpression inhibited beta1 maturation, thus leading to a decrease in the levels of mature beta1 in T-REx HeLa cells, whereas RNA interference-mediated knockdown of ACER2 enhanced beta1 maturation in MCF-7 cells. ACER2 overexpression decreased the cell surface levels of beta1 integrins, thus inhibiting cell adhesion to fibronectin or collagen, whereas ACER2 knockdown has the opposite effects. Treatment with all-trans retinoic acid (ATRA) increased both the expression of ACER2 and the generation of sphingosine in HeLa cells and inhibited beta1 maturation. ACER2 knockdown attenuated the inhibitory effects of ATRA on both beta1 maturation and cell adhesion. In contrast, treatment with phorbol myristate acetate (PMA), a protein kinase C activator, decreased the expression of ACER2 and sphingosine in T-REx HeLa cells, thus enhancing beta1 maturation. ACER2 overexpression inhibited the stimulatory effects of PMA on both beta1 maturation and cell adhesion. These results suggest that the ACER2/sphingosine pathway plays an important role in regulating beta1 maturation and cell adhesion mediated by beta1 integrins. | 18,945,876 |
Abeta oligomers induce neuronal cell cycle events in Alzheimer's disease. | Neurons subject to degeneration in Alzheimer's disease (AD) exhibit evidence of re-entry into a mitotic cell cycle even before the development of substantial AD brain pathology. In efforts to identify the initiating factors underlying these cell cycle events (CCEs), we have characterized the appearance of the neuronal CCEs in the genomic-based R1.40 transgenic mouse model of AD. Notably, R1.40 mice exhibit neuronal CCEs in a reproducible temporal and spatial pattern that recapitulates the neuronal vulnerability seen in human AD. Neuronal CCEs first appear at 6 months in the frontal cortex layers II/III. This is 6-8 months before detectable amyloid beta (Abeta) deposition, suggesting that specific amyloid precursor protein (APP) processing products are responsible for the induction of neuronal CCEs. Furthermore, a reduction in the levels of Abeta (achieved by shifting the genetic background from C57BL/6 to the DBA/2 mouse strain) dramatically delays the appearance of neuronal CCEs. More significantly, elimination of beta-secretase activity blocks the appearance of CCEs, providing direct genetic evidence that the amyloidogenic processing of APP is required for the induction of CCEs. Finally, in vitro preparations of oligomeric, but not monomeric, Abeta induce DNA synthesis in dissociated cortical neurons, and this response is blocked by antioligomer specific antibodies. Together, our data suggest that low molecular weight aggregates of Abeta induce neuronal cell cycle re-entry in mouse models of Alzheimer's disease. | 18,945,886 |
Neonatal neuronal circuitry shows hyperexcitable disturbance in a mouse model of the adult-onset neurodegenerative disease amyotrophic lateral sclerosis. | Distinguishing the primary from secondary effects and compensatory mechanisms is of crucial importance in understanding adult-onset neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Transgenic mice that overexpress the G93A mutation of the human Cu-Zn superoxide dismutase 1 gene (hSOD1(G93A) mice) are a commonly used animal model of ALS. Whole-cell patch-clamp recordings from neurons in acute slice preparations from neonatal wild-type and hSOD1(G93A) mice were made to characterize functional changes in neuronal activity. Hypoglossal motoneurons (HMs) in postnatal day 4 (P4)-P10 hSOD1(G93A) mice displayed hyperexcitability, increased persistent Na(+) current (PC(Na)), and enhanced frequency of spontaneous excitatory and inhibitory transmission, compared with wild-type mice. These functional changes in neuronal activity are the earliest yet reported for the hSOD1(G93A) mouse, and are present 2-3 months before motoneuron degeneration and clinical symptoms appear in these mice. Changes in neuronal activity were not restricted to motoneurons: superior colliculus interneurons also displayed hyperexcitability and synaptic changes (P10-P12). Furthermore, in vivo viral-mediated GFP (green fluorescent protein) overexpression in hSOD1(G93A) HMs revealed precocious dendritic remodeling, and behavioral assays revealed transient neonatal neuromotor deficits compared with controls. These findings underscore the widespread and early onset of abnormal neural activity in this mouse model of the adult neurodegenerative disease ALS, and suggest that suppression of PC(Na) and hyperexcitability early in life might be one way to mitigate or prevent cell death in the adult CNS. | 18,945,894 |
Swiss Cheese, a protein involved in progressive neurodegeneration, acts as a noncanonical regulatory subunit for PKA-C3. | The Drosophila Swiss Cheese (SWS) protein and its vertebrate ortholog Neuropathy Target Esterase (NTE) are required for neuronal survival and glial integrity. In humans, NTE is the target of organophosphorous compounds which cause a paralyzing axonal degeneration and recently mutations in NTE have been shown to cause a Hereditary Spastic Paraplegia called NTE-related Motor-Neuron Disorder. SWS and NTE are concentrated in the endoplasmic reticulum and both have been shown to have an esterase function against an artificial substrate. However, the functional mechanisms and the pathways in which SWS/NTE are involved in are still widely unknown. Here, we show that SWS interacts specifically with the C3 catalytic subunit of cAMP activated protein kinase (PKA-C3), which together with orthologs in mouse (Pkare) and human (PrKX) forms a novel class of catalytic subunits of unknown function. This interaction requires a domain of SWS which shows homology to regulatory subunits of PKA and, like conventional regulatory subunits, the binding of SWS to the PKA-C3 inhibits its function. Consistent with this result, expression of additional PKA-C3 induces degeneration and enhances the neurodegenerative phenotype in sws mutants. We also show that the complex formation with the membrane-bound SWS tethers PKA-C3 to membranes. We therefore propose a model in which SWS acts as a noncanonical subunit for PKA-C3, whereby the complex formation regulates the localization and kinase activity of PKA-C3, and that disruption of this regulation can induce neurodegeneration. | 18,945,896 |
Turning astrocytes from the rostral migratory stream into neurons: a role for the olfactory sensory organ. | Neurogenesis persists within a few restricted areas of the adult mammalian brain, giving rise to neurons that functionally integrate into preexisting circuits. One of these areas, the subventricular zone (SVZ), was believed, until recently, to be the unique source providing the adult olfactory bulb (OB) with newborn neurons. Because of the fact that neuroblasts derived in the SVZ migrate through the rostral migratory stream (RMS) en route to the OB, the existence of candidate neural stem cells within the RMS was long overlooked. Here, we confirm and considerably extend recent evidence for the existence of adult neural stem cells within the RMS, and go on to investigate their proliferative regulation. Specifically targeting RMS-astrocytes with lentiviral vectors encoding GFP, we demonstrate that glial cells in the RMS differentiate into both OB granule and periglomerular interneurons. In addition, ultrastructural analysis unambiguously reveals the astrocytic nature of stem cells in the adult RMS, and patch-clamp recordings demonstrate the functional integration of RMS-derived interneurons into OB circuitry. Proliferative regulation was investigated via two contrasting manipulations: exposure to an odor-enriched environment that enhances candidate stem cell proliferation in both the RMS and SVZ, and chemical lesion of the main olfactory epithelium that increases cell proliferation in the RMS only. New neurons in the adult OB can therefore arise from different neurogenic areas that can be separately regulated. | 18,945,916 |
Comparison of once- versus twice-daily administration of insulin detemir, used with mealtime insulin aspart, in basal-bolus therapy for type 1 diabetes: assessment of detemir administration in a progressive treat-to-target trial (ADAPT). | The purpose of this study was to compare effects of insulin detemir once daily versus twice a day in a basal-bolus insulin regimen. In this open-label, 7-month study, 520 patients with type 1 diabetes were randomly assigned to receive detemir once daily or twice daily with mealtime insulin aspart. Insulin doses were titrated over 1 month, with patients followed up over the subsequent 3 months. Thereafter, patients were able to switch from one regimen to the other, with an additional nonrandomized 3-month follow-up, to a total of 7 months. The primary end point was A1C at 4 months, with noninferiority defined as a difference <0.4% between groups. A1C at 4 months was 8.1 +/- 0.9 versus 8.0 +/- 1.0% with once- and twice-daily detemir, respectively, with an adjusted between-group difference of 0.12% (95% CI -0.01 to 0.25%), showing noninferiority for once-daily dosing. Similar results were found in the per protocol population. Improvement in A1C was similar in both groups (-0.4 +/- 0.8 vs. -0.5 +/- 0.8%; P = 0.09, NS) but with differences in the 7-point glucose profile. Detemir doses were lower (29 +/- 18 vs. 39 +/- 20 units/day, P < 0.001), but aspart doses were higher (34 +/- 17 vs. 26 +/- 14 IU/day, P < 0.001) with once-daily detemir. At 7 months, A1C decreased slightly in patients switched from once-daily to twice-daily administration (8.2 +/- 0.8 vs. 8.0 +/- 0.8%; P = 0.34, NS) in association with increased total insulin doses (P < 0.05), but A1C increased in those switched from twice-daily to once-daily administration (7.2 +/- 0.9 vs. 7.6 +/- 0.8%, P < 0.05) in association with decreased doses (P < 0.05). Although some individuals may benefit from twice-daily dosing, the most suitable routine starting schedule for detemir in a basal-bolus regimen for type 1 diabetes is once-daily injection. | 18,945,928 |
Sprouting of substance P-expressing primary afferent central terminals and spinal micturition reflex NK1 receptor dependence after spinal cord injury. | The primary afferent neurotransmitter triggering the spinal micturition reflex after complete spinal cord injury (SCI) in the rat is unknown. Substance P detected immunohistochemically in the sacral parasympathetic nucleus was significantly higher in 12 SCI rats than in 12 spinally intact rats (P = 0.008), suggesting substance P as a plausible candidate for the primary afferent neurotransmitter. The effects of the tachykinin NK1 receptor antagonist L-733060 on the spinal micturition reflex were then determined by performing conscious cystometry in an additional 14 intact rats and 14 SCI rats with L-733060 (0.1-100 microg) administered intrathecally at L6-S1. L-733060 was without effect in intact rats, but blocked the spinal micturition reflex in 10 of 14 SCI rats and increased the intermicturition interval in 2 of 4 others at doses ranging from 10 to 100 microg. Both phasic and nonphasic voiding contractions, differentiated according to the presence of phasic external urethral sphincter (EUS) activity, were present in most SCI rats. Both types of contractions were blocked by high doses of L-733060. Interestingly, there was a relative decline in phasic voiding contractions at high doses as well as a decline in contraction amplitude in nonphasic voiding contractions. In other respects, cystometric variables were largely unaffected in either spinally intact or SCI rats. L-733060 did not affect tonic EUS activity at any dose except when the spinal micturition reflex was blocked and tonic activity was consequently lost. These experiments show that tachykinin action at spinal NK1 receptors plays a major role in the spinal micturition reflex in SCI rats. | 18,945,947 |
Afferent renal denervation impairs baroreflex control of efferent renal sympathetic nerve activity. | Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which decreases ERSNA to prevent sodium retention. High-sodium diet enhances ARNA, suggesting an important role for ARNA in suppressing ERSNA during excess sodium intake. Mean arterial pressure (MAP) is elevated in afferent renal denervated by dorsal rhizotomy (DRX) rats fed high-sodium diet. We examined whether the increased MAP in DRX is due to impaired arterial baroreflex function. In DRX and sham DRX rats fed high-sodium diet, arterial baroreflex function was determined in conscious rats by intravenous nitroprusside and phenylephrine or calculation of transfer function gain from arterial pressure to ERSNA (spontaneous baroreflex sensitivity). Increasing MAP did not suppress ERSNA to the same extent in DRX as in sham DRX, -60 +/- 4 vs. -77 +/- 6%. Maximum gain, -4.22 +/- 0.45 vs. -6.04 +/- 0.90% DeltaERSNA/mmHg, and the maximum value of instantaneous gain, -4.19 +/- 0.45 vs. -6.04 +/- 0.81% DeltaERSNA/mmHg, were less in DRX than in sham DRX. Likewise, transfer function gain was lower in DRX than in sham DRX, 3.9 +/- 0.2 vs. 6.1 +/- 0.5 NU/mmHg. Air jet stress produced greater increases in ERSNA in DRX than in sham DRX, 35,000 +/- 4,900 vs. 20,900 +/- 3,410%.s (area under the curve). Likewise, the ERSNA responses to thermal cutaneous stimulation were greater in DRX than in sham DRX. These studies suggest impaired arterial baroreflex suppression of ERSNA in DRX fed high-sodium diet. There were no differences in arterial baroreflex function in DRX and sham DRX fed normal-sodium diet. Impaired arterial baroreflex function contributes to increased ERSNA, which would eventually lead to sodium retention and increased MAP in DRX rats fed high-sodium diet. | 18,945,951 |
Role of the hypothalamic PVN in the reflex reduction in mesenteric blood flow elicited by hyperthermia. | The hypothalamic paraventricular nucleus (PVN) is an important integrative center in the brain. In the present study, we investigated whether the PVN is a key region in the mesenteric vasoconstriction that normally accompanies an increase in core body temperature. Anesthetized rats were monitored for blood pressure, heart rate, mesenteric blood flow, and vascular conductance. In control rats, elevation of core body temperature to 41 degrees C had no significant effect on blood pressure, increased heart rate, and reduced mesenteric blood flow by 21%. In a separate group of rats, muscimol was microinjected bilaterally (1 nmol/side) into the PVN. Compared with the control group, there was no significant difference in the blood pressure and heart rate responses elicited by the increase in core body temperature. In contrast to control animals, however, mesenteric blood flow did not fall in the muscimol-treated rats in response to the elevation in core body temperature. In a separate group, in which muscimol was microinjected into regions outside the PVN, elevating core body temperature elicited the normal reduction in mesenteric blood flow. The results suggest that the PVN may play a key role in the reflex decrease in mesenteric blood flow elicited by hyperthermia. | 18,945,952 |
ACE2 expression and activity are enhanced during pregnancy. | In the current study, we investigated the expression and activity of ACE2 during pregnancy in normotensive and hypertensive rats, focusing on the relative contribution of the uterus and the placentas, the kidney serving as a reference. We used the Sabra rat model of salt-sensitive hypertension. We confirmed a systemic vasodilatory state during the third trimester of pregnancy, as evidenced by a reduction in blood pressure, both in normotensive and hypertensive rats. At the time that blood pressure was reduced, ACE2 was expressed abundantly in the reproductive organs. The relative levels of ACE2 mRNA in the pregnant animal were placenta > kidneys > or = uterus and of ACE2 activity kidney > placenta > uterus. In the uterus and the placenta, ACE2 expression was unaffected by strain, salt-loading, or the level of blood pressure. ACE2 activity in the uterus of the nonpregnant rat was not affected by any of these variables either, but during pregnancy increased in salt-loaded animals. When estimating the total contribution of the uterus to ACE2 mRNA and activity during pregnancy, we found that the amount of ACE2 mRNA increased in both strains irrespective of diet, but that ACE2 activity increased only in salt-loaded animals. We further estimated the relative total contribution of the uterus, placentas, and kidneys to ACE2 expression and activity during pregnancy by adjusting for mass and number of organs and found that the placentas were the major contributors, followed by the kidney and the uterus. We conclude that during pregnancy, the placentas, in particular, but also the uterus, constitute important sources of ACE2, in addition to its normal production in the kidney, leading to an estimated twofold increase in total ACE2 activity. These data are consistent the hypothesis that transient ACE2 overexpression and increased activity during pregnancy may be important in modulating systemic, as well as local hemodynamics in the uteroplacental unit. | 18,945,956 |
Effects of eradication of Helicobacter pylori infection in patients with immune thrombocytopenic purpura: a systematic review. | Whether the eradication of Helicobacter pylori infection can increase the platelet count in patients with immune thrombocytopenic purpura (ITP) is still a controversial issue. To provide evidence-based guidance, we performed a systematic review of the literature published in English, selecting articles reporting 15 or more total patients. We identified 25 studies including 1555 patients, of whom 696 were evaluable for the effects of H pylori eradication on platelet count. The weighted mean complete response (platelet count > or = 100 x 10(9)/L) and overall response (platelet count > or = 30 x 10(9)/L and at least doubling of the basal count) were 42.7% (95% confidence interval [CI], 31.8%-53.9%) and 50.3% (95% CI, 41.6%-59.0%), respectively. In 222 patients with a baseline platelet count less than 30 x 10(9)/L, the complete response rate was 20.1% (95% CI, 13.5%-26.7%) and the overall response rate was 35.2% (95% CI, 28.0%-42.4%). The response rate tended to be higher in countries with a high background prevalence of H pylori infection and in patients with milder degrees of thrombocytopenia. These findings suggest that the detection and eradication of H pylori infection should be considered in the work-up of patients with seemingly typical ITP. | 18,945,961 |
Anti-leukemia activity of alloreactive NK cells in KIR ligand-mismatched haploidentical HSCT for pediatric patients: evaluation of the functional role of activating KIR and redefinition of inhibitory KIR specificity. | We analyzed 21 children with leukemia receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT) from killer immunoglobulin (Ig)-like receptors (KIR) ligand-mismatched donors. We showed that, in most transplantation patients, variable proportions of donor-derived alloreactive natural killer (NK) cells displaying anti-leukemia activity were generated and maintained even late after transplantation. This was assessed through analysis of donor KIR genotype, as well as through phenotypic and functional analyses of NK cells, both at the polyclonal and clonal level. Donor-derived KIR2DL1(+) NK cells isolated from the recipient displayed the expected capability of selectively killing C1/C1 target cells, including patient leukemia blasts. Differently, KIR2DL2/3(+) NK cells displayed poor alloreactivity against leukemia cells carrying human leukocyte antigen (HLA) alleles belonging to C2 group. Unexpectedly, this was due to recognition of C2 by KIR2DL2/3, as revealed by receptor blocking experiments and by binding assays of soluble KIR to HLA-C transfectants. Remarkably, however, C2/C2 leukemia blasts were killed by KIR2DL2/3(+) (or by NKG2A(+)) NK cells that coexpressed KIR2DS1. This could be explained by the ability of KIR2DS1 to directly recognize C2 on leukemia cells. A role of the KIR2DS2 activating receptor in leukemia cell lysis could not be demonstrated. Altogether, these results may have important clinical implications for the selection of optimal donors for haplo-HSCT. | 18,945,967 |
Model curriculum for academic child and adolescent psychiatry training. | The United States is facing a severe shortage of academic child and adolescent psychiatrists. This article reviews a model integrated pathway to improve recruitment. The authors review training portals for research in child and adolescent psychiatry. There is a summary of a focus group discussion of the advantages and disadvantages of the Integrated Research Pathway in Child and Adolescent Psychiatry (IRPCAP). The University of Colorado and Yale University have initiated integrated pathways. These pathways integrate research into a 5 or 6-year residency to train the next generation of physician-scientists. The innovative Integrated Research Pathway in Child and Adolescent Psychiatry training model has enhanced recruitment of talented physician-scientists. Challenges include long-term financial viability and incorporating all training requirements. Novel pilot models of training are encouraged. | 18,945,975 |
Utility of estimated glomerular filtration rate in live kidney donation. | Live kidney donation is considered safe; nevertheless, data supporting such claims are almost exclusively of white origin with very limited long-term outcomes in ethnic minority donors. This prospective observational study consisted of a total of 103 previous kidney donors (54 black and 49 white) with mean follow-up days of 743.5 +/- 603.9 for white and 845.1 +/- 668.5 for black donors. The black donors had a statistically significant greater loss of estimated GFR (eGFR; 39.8 ml/min per 1.73 m2) in comparison with white donors (30.4 ml/min per 1.73 m2; P = 0.001). In multivariate analysis, predonation eGFR of <100 ml/min and age at the time of donation were the significant predictors for postdonation eGFR <60 ml/min among black donors. Because eGFR using the Modification of Diet in Renal Disease 4 formula is not validated in live kidney donors, the significance of eGFR <60 ml/min per 1.73 m2 in previous kidney donors is unclear. Long-term prospective study with a gold standard method such as iothalamate GFR measurement is needed to define the actual decrease in eGFR after kidney donation. | 18,945,996 |
Diffusion tensor imaging correlates of memory and language impairments in temporal lobe epilepsy. | To investigate the relationship between white matter tract integrity and language and memory performances in patients with temporal lobe epilepsy (TLE). Diffusion tensor imaging (DTI) was performed in 17 patients with TLE and 17 healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) were calculated for six fiber tracts (uncinate fasciculus [UF], arcuate fasciculus [AF], fornix [FORX], parahippocampal cingulum [PHC], inferior fronto-occipital fasciculus [IFOF], and corticospinal tract [CST]). Neuropsychological measures of memory and language were obtained and correlations were performed to evaluate the relationship between DTI and neuropsychological measures. Hierarchical regression was performed to determine unique contributions of each fiber tract to cognitive performances after controlling for age and hippocampal volume (HV). Increases in MD of the left UF, PHC, and IFOF were associated with poorer verbal memory in TLE, as were bilateral increases in MD of the AF, and decreases in FA of the right AF. Increased MD of the AF and UF, and decreased FA of the AF, UF, and left IFOF were related to naming performances. No correlations were found between DTI measures and nonverbal memory or fluency in TLE. Regression analyses revealed that several fibers, including the AF, UF, and IFOF, independently predicted cognitive performances after controlling for HV. The results suggest that structural compromise to multiple fiber tracts is associated with memory and language impairments in patients with temporal lobe epilepsy. Furthermore, we provide initial evidence that diffusion tensor imaging tractography may provide clinically unique information for predicting neuropsychological status in patients with epilepsy. | 18,946,001 |
Microstructural changes in fat during the ripening of Iranian ultrafiltered Feta cheese. | In this study, fat globules in Iranian ultrafiltered Feta cheese (3 to 60 d) were directly observed during the ripening period by scanning electron microscopy. According to images of ultrafiltered Feta cheese samples obtained by scanning electron microscopy, individual fat globules and aggregates of fat were easily distinguishable on d 3 and had completely disappeared within 20 d of storage. On d 20, only the fingerprints of the fat globules and pools of free fat in the casein matrix remained. After 40 d of ripening, the texture was homogeneous and no fat globules or fat voids were detected. Chemical analysis of cheese samples showed that with an increase in the ripening period, the contents of dry matter and fat decreased significantly, whereas the pH values and salt content did not indicate any significant changes. | 18,946,118 |
An observational analysis of twin births, calf stillbirth, calf sex ratio, and abortion in Iranian holsteins. | Calving records of Holstein dairy cows from April 1998 to September 2006 comprising 16 herds with 104,572 calving events representing 4,045 twin births were used to evaluate reported twinning rate, calf sex ratio, stillbirth, and abortion rates in single and twin births. Overall, the reported twinning rate was 3.9%, and twinning increased with parity [1.1% for primiparous cows vs. 5.7% for cows in their fourth or greater lactation; odds ratio (OR) = 5.50]. Regardless of parity, the greatest twinning rate was observed when conception occurred in fall season from September to December (OR = 1.17). Calf stillbirth was greater after twin births, with 18.8% of twin calving events resulting in one or both calves as stillborn, compared with 4.0% for singleton births (OR = 7.58). Calf stillbirth for multiparous cows was 2.9% for single births and 18.0% for twin births (OR = 7.08), whereas for primiparous cows, stillbirth was 6.6% for singletons and 27.7% for twins (OR = 5.85). Calf sex ratios (male, M; female, F) were 52.4% M and 47.6% F for singleton calves and 28.2% MM, 48.9% MF, and 22.9% FF for twin calves. The mean abortion rate was 13.4%, with 13.8% for single births and 4.2% for twin births (OR = 1.22). Abortion rate for multiparous cows was 15.9% for single births and 4.0% for twin births (OR = 4.31), whereas for primiparous cows, abortion rate was 9.4% for single births and 5.4% for twin births (OR = 1.89). Although milk production, as a causative factor associated with twinning, increased in recent years, twinning rate decreased over the years. | 18,946,124 |
Genetic and phenotypic relationships among milk urea nitrogen, fertility, and milk yield in holstein cows. | The aims of the study were to evaluate the relationships among milk urea nitrogen and nonreturn rates at the phenotypic scale, and to estimate genetic parameters among milk urea nitrogen, milk yield, and fertility traits in the early period of lactation. Milk yield, protein percentage, the interval from calving to first service, and 56- and 90-d nonreturn rates were available from 73,344 Holstein cows from 2,178 different herds located in a region in northwestern Germany. Generalized linear models with a logit link function were applied to assess the phenotypic relationships. Bivariate threshold-threshold, linear-threshold, and linear-linear models, fitted in a Bayesian framework, were used to estimate genetic correlations among traits. Milk yield, protein percentage, and milk urea nitrogen were means from test-day 1 (on average 20.8 d in milk) and test-day 2 (on average 53.1 d in milk) after calving. An increase in milk urea nitrogen was associated with decreasing 56-d nonreturn rates on the phenotypic scale. At fixed levels of milk urea nitrogen, greater values of protein percentage, indicating a surplus of energy in the feed, were positively associated with nonreturn rates. Heritabilities were 0.03 for 56- and 90-d nonreturn rates, 0.07 for interval from calving to first service, 0.13 for milk urea nitrogen, and 0.19 for milk yield. Service sire explained a negligible part (below 0.15%) of the total variance for nonreturn rates. Genetic correlations between the interval from calving to first service and nonreturn rates were close to zero. The genetic correlation between nonreturn rates was 0.94, suggesting that a change from nonreturn after 90 d to nonreturn after 56 d in the national genetic evaluation would not result in any loss of information. The genetic correlation between milk yield and nonreturn after 56 d was -0.31, and between milk yield and calving to first service was 0.14, both indicating an antagonistic relationship between production and reproduction. The genetic correlation between milk yield and milk urea nitrogen was 0.44, reflecting an energy deficiency in early lactation. The genetic correlations between milk urea nitrogen and nonreturn rates were too weak (-0.19 for 56-d nonreturn rate, and -0.23 for 90-d nonreturn rate) to justify the use of milk urea nitrogen as an additional trait in genetic selection for fertility, as demonstrated by selection index calculations. | 18,946,143 |
Adaptive singular value cancelation of ventricular activity in single-lead atrial fibrillation electrocardiograms. | The proper analysis and characterization of atrial fibrillation (AF) from surface electrocardiographic (ECG) recordings requires to cancel out the ventricular activity (VA), which is composed of the QRS complex and the T wave. Historically, for single-lead ECGs, the averaged beat subtraction (ABS) has been the most widely used technique. However, this method is very sensitive to QRST wave variations and, moreover, high-quality cancelation templates may be difficult to obtain when only short length and single-lead recordings are available. In order to overcome these limitations, a new QRST cancelation method based on adaptive singular value cancelation (ASVC) applied to each single beat is proposed. In addition, an exhaustive study about the optimal set of complexes for better cancelation of every beat is also presented for the first time. The whole study has been carried out with both simulated and real AF signals. For simulated AF, the cancelation performance was evaluated making use of a cross-correlation index and the normalized mean square error (nmse) between the estimated and the original atrial activity (AA). For real AF signals, two additional new parameters were proposed. First, the ventricular residue (VR) index estimated the presence of ventricular activity in the extracted AA. Second, the similarity (S) evaluated how the algorithm preserved the AA segments out of the QRST interval. Results indicated that for simulated AF signals, mean correlation, nmse, VR and S values were 0.945 +/- 0.024, 0.332 +/- 0.073, 1.552 +/- 0.386 and 0.986 +/- 0.012, respectively, for the ASVC method and 0.866 +/- 0.042, 0.424 +/- 0.120, 2.161 +/- 0.564 and 0.922 +/- 0.051 for ABS. In the case of real signals, the mean VR and S values were 1.725 +/- 0.826 and 0.983 +/- 0.038, respectively, for ASVC and 3.159 +/- 1.097 and 0.951 +/- 0.049 for ABS. Thus, ASVC provides a more accurate beat-to-beat ventricular QRST representation than traditional techniques. As a consequence, VA cancelation is optimized and the AA can be extracted more precisely. Finally, the study has proven that optimal VA cancelation is achieved when a number between 20 and 30 complexes is selected following a correlation-based strategy. | 18,946,157 |
Sediment monitoring and the European Water Framework Directive. | Sediment is an essential, integral and dynamic part of our river basins. A healthy river needs sediment as a source of life. Unfortunately, sediment also acts as a potential sink for many hazardous chemicals. Above a certain level of contamination this will result in negative impacts such a loss of biodiversity. This is deemed intolerable by society and hence the European Water Framework Directive (WFD) was developed. The WFD aims to achieve a good status of all European waters by the year 2015. The WFD does not specifically deal with sediment although it is clear that there is a link between sediment quality and achieving of this WFD objective. However, related to sediment monitoring there are some direct links in the WFD, which are further explained in this paper. | 18,946,159 |
Risk management of sediments. | Sediment management nowadays is often concerned around sediments that have been polluted in former times, posing the following questions: what risks remain after time has passed concerning the persistence, ageing and bioavailability of the polluting substances; where does the risk apply regarding the transport of contaminated sediments and the management objectives in the different zones of a river basin; how can solutions be found; who is responsible for paying the management measures. This publication reflects on the discussions in the SedNet Working Group on "risk management and communication" claiming that sustainable sediment management needs to be risk based and oriented towards the river basin scale. Results of two case studies are recounted, which roughly followed the site prioritization approach that was suggested by the participants of the working group and gives an example on a decision making module that could help in communicating interests and the resulting priorities of measures, after areas of risks have been identified in a river basin. | 18,946,160 |
Attenuation of cardioprotective effect by postconditioning in coronary stenosed rat heart and its restoration by carvedilol. | The aim of this study was to assess whether and how infarct size (IS) reduction by postconditioning is modified in the heart with coronary stenosis (CS), and how beta-blocker treatment affects it. The IS was assessed by 30-min acute coronary occlusion and 24-h reperfusion in rat hearts in which CS had been induced. Modification of IS by postconditioning and the effects of daily carvedilol treatment were measured, together with reperfusion injury - salvage kinase activities. Four weeks after CS induction, any reduction of IS by postconditioning was lost, whereas it reduced IS in rats without CS. In the hearts without CS, postconditioning activated both the ERK and Akt pathway. However, in the hearts with CS, postconditioning failed to do so. In hearts with CS plus daily carvedilol treatment, postconditioning reduced IS compared with the hearts without carvedilol, although postconditioning did not activate the Akt and ERK pathways. CS impaired Akt and ERK activation, resulting in a failure to reduce IS by postconditioning. Carvedilol treatment restored the IS reduction by postconditioning, possibly via other mechanism(s) of the ERK and Akt pathways. | 18,946,174 |
Establishing EGFP congenic mice in a NOD/Shi-scid IL2Rg(null) (NOG) genetic background using a marker-assisted selection protocol (MASP). | Severely immunocompromised NOD/Shi-scid IL2Rg (null) (NOG) mice, which show higher engraftment efficiency, are useful as recipients in xenotransplantation studies. We generated a NOG-enhanced green fluorescent protein (EGFP) transgenic (Tg) mouse (NOG-EGFP) that was introduced the EGFP transgene from the C57BL/6-EGFP Tg mouse using the speed congenic method with a marker-assisted selection protocol (MASP). With this method, the selection of the male with the closest NOG strain type was repeated four times. When human cord blood CD34(+) cells were transplanted into NOD/Shi-scid, NOG, and NOG-EGFP mice (N(6)), the engraftment efficiency of the NOG-EGFP mice was significantly higher than that of the NOD/Shi- scid mice and was similar to that of the NOG mice. These results suggest that the NOG-EGFP mice, which were generated using the congenic method with MASP, acquired the immunological properties of the NOG mice. | 18,946,184 |
Hyperlipidemia in rabbit hemorrhagic disease. | Clinically healthy rabbits were inoculated with rabbit hemorrhagic disease virus (RHDV) and the kinetics of their serum lipid parameters and liver enzymes were monitored. After RHDV inoculation, hyperlipidemia was observed (P(triglyceride)<0.0001, P(cholesterol)=0.0003) along with significant increases in serum aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase (P<0.0001). An exponential increase in serum triglyceride was also seen. Thus, the presence of hyperlipidemia (from 30 h post-inoculation) in the infected rabbits points to impairment in lipid metabolism. This is the first demonstration that RHDV infection leads to hyperlipidemia, probably due to the disorder of liver enzymes associated with lipid metabolism. | 18,946,185 |
Separate recording of A-delta and C fiber-mediated nociceptive flexor reflex responses of mouse hindlimb using electromyography and the characteristics of wind-up appearing in the responses. | To measure separately electromyogram (EMG) activity of A-delta and C fiber-mediated responses and study the characteristics of drug effects on them in mice, we modified our original method designed to measure these responses associated with hindlimb withdrawal movements. Single electrical stimulation applied to the toe elicited biphasic EMG activity in the ipsilateral femoris biceps muscle and withdrawal movement. Times to peak of the short- and long-latency response of EMG activity were almost consistent with those obtained from the hindlimb movement. As the short- and the long-latency responses of EMG activity were selectively inhibited by tetrodotoxin (TTX) (3 and 10 muM) and capsaicin (0.98 and 3.27 mM) applied to the sciatic nerve, the responses were considered to occur via A-delta and C fibers, respectively. A 0.5-Hz repetitive conditioning stimulus (CS) elicited significant wind-up in both the A-delta and C fiber-mediated responses. The wind-up of the A-delta fiber-mediated response disappeared during the CS and that of the C fiber-mediated response continued throughout the CS. This method is simple but useful for studying the effect of analgesic agents on A-delta and C fiber-mediated nociceptive responses and clarifying the roles of these afferent fibers in chronic pain in mice. | 18,946,194 |
Treatment of folliculitis with monochromatic excimer light (308 nm). | 308-nm excimer light has been reported to be safe and effective in the treatment of chronic skin diseases. The aim of the study was to prove the efficacy of 308-nm monochromatic excimer light in the treatment of recalcitrant and antibiotic-resistant folliculitis. Eight patients affected with folliculitis were enrolled and treated twice weekly with the 308-nm excimer light. The follow-up was 12 weeks from the end of the treatment. A mean number of 13 sessions (range 10-20) was performed with increasing dosage according to the patient's photo-type and response. Remission, in terms of number and infiltration of papulopustular elements, was achieved in all patients after 4-16 therapeutic sessions. At the end of the follow-up period, recurrence of folliculitis was observed in 2 patients. These results suggest that the 308-nm excimer light is a valid therapeutic option for the treatment of resistant forms of folliculitis especially in difficult-to-treat areas. | 18,946,200 |
Navigational experience affects hippocampus size in homing pigeons. | Homing (racing) pigeons (Columba livia f.d.) are well-known for their homing abilities, which are thought to be based on a genetic predisposition, multimodal learning and spatial cognition. On average, the hippocampus, a forebrain structure that processes spatial information, is larger in homing pigeons compared to other non-homing pigeon breeds or their wild ancestor, the rock dove. Here we show that this characteristic hippocampus volume is dependent on flying and navigational experience. Twenty homing pigeons originating from the same breeding stock were raised in the same loft under identical constraints. After fledging, 10 of them were allowed to fly around the loft, gain navigational experience and participate successfully in races. The other 10 stayed permanently in the loft and thus did not share the navigational skill experienced by the first group. After reaching sexual maturity, individuals of both groups were sacrificed and morphometric analyses were carried out to measure the volumes of total brain, telencephalon, hippocampus and 12 other brain structures. Individuals with experience in flying and navigation had an 11.2% larger hippocampus relative to the telencephalon compared to non-experienced individuals (p = 0.028). This effect is not seen in any of the other measured brain subdivisions. Given that plasticity in hippocampal volume has a genetic component, our results confirm that there is also an experience component, and that has certain implications for navigational ability. Evidently, experience is a precondition to full hippocampal development. | 18,946,210 |
Quantitative evaluation of carotid plaque echogenicity by integrated backscatter analysis: correlation with symptomatic history and histologic findings. | Echogenicity of carotid plaque well reflects the risk of ischemic stroke and may be predictive of the histologic content of the plaque. However, objective evaluation of plaque echogenicity has been hampered by a lack of established quantitative measures. This study examined the relation between echogenicity assessed by integrated backscatter (IBS) analysis and (1) symptomatic history and (2) histologic features of carotid plaques. We used acoustic densitometry to quantify by IBS analysis the echogenicity of 31 carotid plaques of 26 patients undergoing carotid endarterectomy or stenting. IBS was subsequently compared with histologic findings of the respective tissue in 10 patients who underwent endarterectomy. The IBS value was calibrated with 2 reference structures (vessel lumen and adventitia) as the IBS index. The IBS index of symptomatic plaques was lower than that of asymptomatic plaques (23.1 +/- 12.5 vs. 36.5 +/- 18.2, p < 0.05). The IBS index in fatty/necrotic atheromatous sites (n = 20, 16.6 +/- 10.7) was lower than that in fibrous (n = 26, 42.4 +/- 13.6, p < 0.01) or calcified (n = 11, 87.7 +/- 17.4, p < 0.01) sites and the same as that in intraplaque hemorrhagic sites (n = 50, 23.6 +/- 16.9). Carotid plaque echogenicity, as quantitatively assessed by IBS analysis, correlates well with the presence or absence of prior symptoms and histologic contents of the plaques. IBS analysis may aid in the assessment of carotid plaque-related risk of stroke. | 18,946,212 |
Depression after first-ever ischemic stroke: the prognostic role of neuroanatomic subtypes in clinical practice. | The relationship between poststroke depression (PSD) and Oxford Community Stroke Project (OCSP) subtypes is uncertain. 713 first-ever ischemic stroke patients recruited in a multicenter investigation to evaluate prevalence, onset time and severity of PSD. Stroke subtypes were considered as independent predictors of PSD occurrence by logistic regression. Results showed similar prevalence of PSD in stroke subtypes with the exception of TACI. Only patients with total anterior cerebral ischemia (TACI) showed a higher PSD occurrence (OR: 1.76, CI: 1.14-2.71). Multivariate analysis underlined the role of severe functional impairment, previous depressive disorders and female sex. Neither the OCSP subgroups, nor left and right involvement were predictive of PSD. TACI and left-sided strokes were related to higher depression severity scores. In clinical practice, the definition of neuroanatomic subtypes provides little contribution specifically to PSD prediction after a first-ever ischemic stroke. | 18,946,214 |
White matter lesion subtypes and cognitive deficits in patients with memory impairment. | To analyze the relationship between periventricular (PV) and subcortical (SC) white matter lesions (WML) and cognitive function in patients with memory impairment. In total, 253 patients with Global Deterioration Scale scores >or=3 who had been referred to a university-based memory unit due to memory complaints were included (mean age 69.7 years, 124 females). Cognitive function was assessed with the Mini-Mental State Examination (MMSE) and the Neurobehavioral Cognitive Status Examination (Cognistat), and full test results were available for 217 patients. PV and SC WML loads (semi-quantitative rating on axial T(2)-weighted MRI scans) were used in linear regression as predictors of cognition. MMSE was significantly correlated with SC WML (p = 0.005), but not with PV WML (p = 0.19). Cognistat tests for orientation, comprehension, visuoconstruction, calculation, similarities, and judgment were negatively correlated with SC WML (p < 0.01), as was verbal memory with parieto-occipital SC WML (p < 0.05). Visuoconstruction and calculation were negatively correlated with PV WML (p < 0.05). Parieto-occipital WML were more strongly related to cognition than fronto-temporal WML. Only SC WML were significantly correlated with cognition when PV and SC WML were entered simultaneously in the regression model. In patients with cognitive impairment, SC WML, in particular in parieto-occipital regions, were associated with reduced cognitive function. | 18,946,220 |
Patterns of drug prescription for Japanese cedar pollinosis using a clinical vignette questionnaire. | Although prescribed drugs directly affect patient outcome, the variation in physicians' attitudes towards drug therapy for cedar pollinosis has not been quantitatively assessed. This research investigated the prescription patterns of drugs for cedar pollinosis by ear, nose, and throat specialists (ENTs), general physicians (GPs) and internal medicine doctors (IMs) in Yamanashi Prefecture, Japan. A cross-sectional study was conducted by mailing questionnaires to 532 physicians in autumn 2006. The main part of the questionnaire constituted clinical vignettes of pollinosis cases with nasal and ocular symptoms ranging from mild to severe. We requested that the physicians fill out prescription medications they considered appropriate for each vignette. Responses from 172 physicians (32%) for six clinical vignettes were analyzed. The number of drugs prescribed by ENTs was significantly higher than that by GPs and IMs for vignettes representing moderate to severe cases (p < 0.004). The percentage of physicians who said they would prescribe nasal corticosteroid and eye drops was higher in the ENT group compared to the other two groups in these vignettes. In terms of second-generation antihistamines, no differences were observed between the three groups for all vignettes. Our investigation suggested that, compared to ENTs, GPs and IMs have a lower tendency to concomitantly prescribe drugs for localized treatment such as nasal corticosteroids and eye drops with oral medication. There may be differences in prescription patterns of drugs for pollinosis between ENTs and non-specialist physicians. | 18,946,236 |
A clinical study of Japanese cedar (Cryptomeria japonica) pollen-induced asthma. | Grass and birch pollens are known to induce asthma. However there are few reports about other pollen-induced asthma. Japanese cedar is the most common allergen in rhinitis in Japan but is controversial on whether it can provoke asthma. To clarify Japanese cedar pollen-induced asthma, we studied adult patients who were sensitized only to the Japanese cedar (CAP-RAST > = 2) and had symptoms of asthma during the cedar season. We defined cedar asthma as a patient who satisfied the 2 criteria mentioned above. We found 6 adult asthma patients who fulfilled the two criteria. Five patients suffered from cedar pollinosis in addition to asthma, and 1 patient had no pollinosis. The cedar pollinosis preceded asthma in 3 cases and occurred at almost the same time in the other 2 cases. Pulmonary function was normal in these cases (FEV 1%, mean +/- SD, 76.5 +/- 10%), with a high threshold value in the non-specific airway hypersensitivity test (Ach-PC20, 2,696 to 20,000 microg/ml, 9294 +/- 2) and low total IgE (101 +/- 86 IU/ml). In the allergen provocation test, 3 subjects showed both an immediate and late asthmatic reaction. We concluded that Japanese cedar pollen could provoke not only pollinosis but also asthma in adults. | 18,946,237 |
Screening for alcohol use and misuse in older adults: using the Short Michigan Alcoholism Screening Test--Geriatric Version. | The Short Michigan Alcoholism Screening Test--Geriatric Version (SMAST-G) is often used in outpatient settings to detect "at-risk" alcohol use, alcohol abuse, or alcoholism in older adults. As the number of older adults in the United States grows, those who develop problems of abuse and a dependence on alcohol will grow as well. The availability of accurate, easy-to-use screening tools to detect people in need of counseling can increase the number of older adults whose lives can be improved and even lengthened. To watch a free online video of a nurse administering the SMAST-G, go to http://links.lww.com/A271. | 18,946,267 |
The Impact of Event Scale--Revised: a quick measure of a patient's response to trauma. | A person may suffer debilitating anxiety and other physical and psychological symptoms without recognizing that they're a response to a traumatic event. And older adults in particular may be reluctant to admit to experiencing such symptoms. The Impact of Event Scale--Revised (IES-R) is an easy-to-administer questionnaire used to evaluate the degree of distress a patient feels in response to trauma. It provides a structured way for a patient to communicate distress when she or he may not have the words to do so. For a free online video showing nurses using the IES-R with an older patient, go to http://links.lww.com/A316. | 18,946,269 |
Metoclopramide does not attenuate cricoid pressure-induced relaxation of the lower esophageal sphincter in awake volunteers. | The authors examined the influence of metoclopramide on cricoid pressure-induced relaxation of the lower esophageal sphincter (LES) in awake human volunteers. With local institutional review board approval, measurements of LES and intragastric pressures were made in 10 consenting volunteers before cricoid pressure application, during 15 s of cricoid pressure application, and after release of cricoid pressure. The measurements were repeated after 0.15 mg/kg intravenous metoclopramide. Cricoid pressure was applied by one investigator trained to consistently apply a force of 44 N. Cricoid pressure resulted in immediate decrease in LES and barrier pressures from 14.1 +/- 2.9 mmHg to 3.2 +/- 3.7 mmHg and from 9.6 +/- 3.4 mmHg to -1.8 +/- 2.9 mmHg, respectively. These pressures promptly returned to baseline values after release of cricoid pressure. LES and barrier pressures increased after metoclopramide from 14.5 +/- 3.1 to 19.6 +/- 4.7 mmHg and from 10.2 +/- 3.6 to 14.1 +/- 5.5 mmHg, respectively. Cricoid pressure applied after metoclopramide resulted in immediate decreases in LES and barrier pressures to levels comparable to cricoid pressure before metoclopramide, but immediately returned to precricoid values after release of pressure. The current investigation demonstrates that cricoid pressure reflexly decreases LES tone and barrier pressure in awake subjects. Although metoclopramide increased LES and barrier pressures, it did not attenuate cricoid pressure-induced relaxation of the LES and barrier pressures and thus seems to have no value in preventing gastroesophageal reflux during cricoid pressure. Metoclopramide may be useful in preventing reflux when there is need to release or discontinue cricoid pressure. | 18,946,291 |
Reversal of profound rocuronium-induced blockade with sugammadex: a randomized comparison with neostigmine. | Traditionally, reversal of nondepolarizing neuromuscular blocking agents was achieved using acetylcholinesterase inhibitors, but these are unable to adequately reverse profound blockade. Sugammadex is a novel reversal agent, reversing the effects of rocuronium by encapsulation. This study assessed the efficacy and safety of sugammadex versus neostigmine for reversal of profound rocuronium-induced neuromuscular blockade. This phase III, randomized study enrolled surgical patients, aged 18 yr or older with American Society of Anesthesiologists physical status I-IV. Patients were randomized to receive sugammadex (4.0 mg/kg) or neostigmine (70 microg/kg) plus glycopyrrolate (14 microg/kg). Anesthetized patients received an intubating dose of rocuronium (0.6 mg/kg), with maintenance doses (0.15 mg/kg) as required. Neuromuscular monitoring was performed by acceleromyography. Sugammadex or neostigmine was administered at reappearance of 1-2 posttetanic counts (profound neuromuscular blockade). The primary efficacy parameter was the time from sugammadex or neostigmine-glycopyrrolate administration to return of the train-of-four ratio to 0.9. In the intent-to-treat population (n = 37 in each group), geometric mean time to recovery to a train-of-four ratio of 0.9 with sugammadex was 2.9 min versus 50.4 min with neostigmine-glycopyrrolate (P < 0.0001) (median, 2.7 min vs. 49.0 min). Most sugammadex patients (97%) recovered to a train-of-four ratio of 0.9 within 5 min after administration. In contrast, most neostigmine patients (73%) recovered between 30 and 60 min after administration, with 23% requiring more than 60 min to recover to a train-of-four ratio of 0.9. Recovery from profound rocuronium-induced neuromuscular blockade was significantly faster with sugammadex versus with neostigmine, suggesting that sugammadex has a unique ability to rapidly reverse profound rocuronium neuromuscular blockade. | 18,946,293 |
The EULAR Scleroderma Trials and Research Group (EUSTAR): an international framework for accelerating scleroderma research. | Systemic sclerosis has a complex pathogenesis and a multifaceted clinical spectrum without a specific treatment. Under the auspices of the European League Against Rheumatism, the European League Against Rheumatism Scleroderma Trials And Research group (EUSTAR) has been founded in Europe to foster the study of systemic sclerosis with the aim of achieving equality of assessment and care of systemic sclerosis patients throughout the world according to evidence-based principles. EUSTAR created the minimal essential data set, a simple two-page form with basic demographics and mostly yes/no answers to clinical and laboratory parameters, to track patients throughout Europe. Currently, over 7000 patients are registered from 150 centres in four continents, and several articles have been published with the data generated by the minimal essential data set. A commitment of EUSTAR is also to teaching and educating, and for this reason there are two teaching courses and a third is planned for early in 2009. These courses have built international networks among young investigators improving the quality of multicentre clinical trials. EUSTAR has organized several rounds of 'teach the teachers' to further standardize the skin scoring. EUSTAR activities have extended beyond European borders, and EUSTAR now includes experts from several nations. The growth of data and biomaterial might ensure many further fruitful multicentre studies, but the financial sustainability of EUSTAR remains an issue that may jeopardize the existence of this group as well as that of other organizations in the world. | 18,946,332 |
Microdialysis monitoring of liver grafts by metabolic parameters, cytokine production, and complement activation. | The outcome of liver transplantation is steadily improving. Still there is need for earlier detection of complications like hepatic artery thrombosis and rejection. The aim of this study was to explore whether microdialysis with a 100-kDa cutoff filter could be used to monitor local inflammation after liver transplantation. Twenty patients undergoing liver transplantations were observed for 1 week posttransplant. Microdialysis catheters were introduced in each liver lobe subcutaneously and metabolic parameters (glucose, pyruvate, glycerol, and lactate), cytokines (interleukin [IL]-6, IL-8, monocyte chemottractic protein-1, and inducible protein [IP]-10), and complement activation (C5a) were measured. Fourteen patients experienced an uneventful course, judged clinically by ultrasound Doppler and by metabolic markers including lactate and the ischemia indicator lactate-to-pyruvate ratio. All patients with uneventful course had a consistent rise in IP-10 from 200 to 3000 pg/mL after transplantation, whereas the other cytokines stayed low. Two patients with rejection showed a selective increase in IL-8 and C5a, starting 2 to 4 days before alanine transferase increased, reaching 10- to 50-fold increase compared with baseline levels, and decreased rapidly after start of antirejection therapy. C5a concentration was substantially increased in these two patients at the time of transplantation. A third patient developed a hepatic artery thrombosis and rejection and showed a rapid rise in intrahepatic lactate and a complex inflammatory pattern. Microdialysis using a 100-kDa filter is a promising way of monitoring the inflammatory reaction after liver transplantation. Increase in IP-10 reflects a normal pathophysiologic response posttransplant, whereas IL-8 and C5a were increased only in patients with rejection. | 18,946,348 |
Postkidney transplant malignancy in Egypt has a unique pattern: a three-decade experience. | The pattern of posttransplant malignancy varies among transplant units. We report on our single-center experience. Between 1976 and 2007, 1866 kidney transplantations were carried out (1390 males and 476 females, mean age 29.84+/-10.47 years). Recipients who developed posttransplant malignancy were evaluated (74 patients, 3.97%). Furthermore, their data were compared with those of the malignancy-free recipients (1792 patients). Kaposi sarcoma was the commonest type (36.8%) and had the shortest transplant-to-malignancy period (mean 2.84 years). The lesions were only cutaneous in 75% of cases. Skin cancers were the fourth among posttransplant malignancies (9.2%) and 85.7% of cases were basal cell carcinoma. In our series, age and prior blood transfusion were identified as independent risk factors for the development of posttransplant malignancy. In conclusion, the prevalence and type of posttransplant malignancy vary because of many factors including environmental and genetic factors. In our series, Kaposi sarcoma was the commonest type and, therefore, needs further evaluation. | 18,946,354 |
High impact of migration on the prevalence of chronic hepatitis B in the Netherlands. | A representative serosurveillance study (1995) resulted in an estimate of 0.2% for the HBsAg prevalence in the Netherlands. Some risk groups, especially migrants, were not well represented in the study, which probably led to an underestimation of the true HBsAg prevalence. The aim of this study was to calculate an adjusted HBsAg prevalence estimate for the total Dutch population including these risk groups. According to their country of origin first-generation migrants (FGM) were classified into groups with low, intermediate and high prevalence using data from the WHO and Statistics Netherlands. The number of chronic HBsAg carriers in different age and population groups was estimated based on studies about age-specific prevalence in different countries. The number of carriers in the indigenous population was estimated using the serosurveillance study. A combination of these estimates led to an estimate of the total prevalence rate in the Netherlands. Nearly 10% of the Dutch population are FGM. Of these, about 18% were born in low-endemic, 71% in middle-endemic and 11% in high-endemic countries. The overall prevalence of HBsAg in FGM is estimated to be at 3.77%. Combining these results with the results of the serosurveillance study the HBsAg prevalence in the Dutch population is estimated to be between 0.32 and 0.51%, and when including injecting drug users and mentally handicapped persons the prevalence rates are 0.36 and 0.55%, respectively. Our results show the high importance of targeting migrants and their close contacts adequately in screening programmes, vaccination and treatment for chronic hepatitis B. | 18,946,359 |
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