Differentially expressed proteins of MCF-7 human breast cancer cells affected by Zilongjin, a complementary Chinese herbal medicine.
Zilongjin, a complementary Chinese herbal medicine, has been used to alleviate the adverse effects of chemotherapeutic drugs in cancer therapy. However, the mechanisms of anti-cancer activity of Zilongjin are still largely unkonwn. First, the proteomic approach of combined 2-DE and ESI-MS/MS was used to investigate the effect of Zilongjin on the protein expression in MCF-7 cells. Then, the differential expression of some proteins was confirmed by Western blot, cytoimmunofluoresecnce, and quantitative real-time RT-PCR analysis. The identified proteins with differential expression, involved in such events as protein translation, cellular signal transduction, cytoskeleton formation and transportation, include seven downregulating proteins, such as Eukaryotic translation initiation factor 3 subunit I, Eukaryotic translation initiation factor 1A Y-chromosomal, Ran-specific GTPase-activating protein, Ubiquitin-conjugating enzyme E2 N, Tropomodulin-3, Macrophage-capping protein, and Tumor protein D52, as well as two upregulating proteins, HSP β-1 and keratin18. Moreover, the differential expression of three proteins was confirmed. (i) These results provide a new insight into the molecular mechanisms of Zilongjin on therapy for breast cancer. (ii) The application of the proteomic approaches will result in the more extended appreciation of Chinese medicine than those known at present.


Exercise metabolism in healthy volunteers taking celiprolol, atenolol, and placebo.
Previous studies have shown that beta 1 selective agents have fewer adverse effects on exercise metabolism than nonselective beta blockers, and this has been attributed to their reduced blockade of beta 2 receptors. This study aimed at determining whether a beta blocker with partial agonist activity at beta 1 and beta 2 receptors (celiprolol) was better than a conventional beta 1 receptor-blocker (atenolol) in prolonging exercise capabilities. After four days of treatment with celiprolol 200 mg, atenolol 50 mg, or placebo, 22 healthy volunteers exercised on a treadmill for two hours at 50% of their maximal oxygen uptake. Resting heart rate and blood pressure were recorded before and after exercise. During exercise, fat oxidation, plasma free fatty acids, glycerol, glucose, and ammonia were measured together with heart rate and perceived exertion. Mean exercising heart rate was significantly lower in those taking either of the beta blockers than in those taking placebo, and significantly lower for those taking atenolol rather than celiprolol. Fat oxidation was significantly lower for those taking celiprolol (38.8 (SD 12.2)%, P < 0.01) and atenolol (36.6 (15.9)%, P < 0.01) compared with placebo (45.6 (14.1)%). For the first 15 minutes of exercise, fat oxidation was significantly lower for those taking atenolol (24.6 (12.8)%, P < 0.01) than celiprolol (29.6 (14.3)%). The rise in plasma free fatty acids and glycerol during exercise was also significantly attenuated by both beta blockers in comparison with the rise in those taking placebo (P < 0.01). Both celiprolol and atenolol reduced fat oxidation compared with placebo. For the first 15 minutes of exercise fat oxidation was preserved by celiprolol, but not atenolol. This preservation of fat oxidation during the early part of exercise may confer some small benefit to patients who take beta blockers and intend to exercise regularly. However, we did not detect significant differences between atenolol and celiprolol in overall mean fat oxidation or perceived exertion in this study.


Acute histoplasmosis in immunocompetent travelers: a systematic review of literature.
Histoplasmosis is a fungal infection highly endemic in the American continent. The disease can be severe in immunocompromised subjects. In immunocompetent subjects the clinical manifestations are variable. Aim of this work was to review the cases of acute histoplasmosis in immunocompetent travelers reported in literature. A systematic review of literature was conducted. Electronic search was performed in Pubmed and LILACS. Two reviewers independently extracted data on demographic, clinical and radiological features, and treatment. Cases were classified according to Wheat's definitions. Seventy-one studies were included in the analysis, comprising a total of 814 patients. Twenty-one patients diagnosed at the Centre of Tropical Diseases, Negrar (VR), Italy were also included. The most common travel destination was Central America (168 people, 29.8%); the most common way of exposure to histoplasma was the exploration of caves and/or contact with bat guano (349 people, 60.9%). The multivariate logistic regression model showed association between the development of disseminated histoplasmosis (DH) and activities that involved the exploration of caves and/or the contact with bats' guano (adjusted OR: 34.20 95% CI: 5.29 to 220.93) or other outdoor activities (adjusted OR: 4.61 95% CI: 1.09 to 19.56). No significant difference in the attack rate between countries of destination was observed (p-value: 0.8906, Kruskal-Wallis test). Histoplasmosis often causes no or mild symptoms in immunocompetent individuals, although a severe syndrome may occur. The infection can mimic other diseases, and the epidemiological risk of exposure is an important clue to raise the index of suspicion.


Identification of novel pepper genes involved in Bax- or INF1-mediated cell death responses by high-throughput virus-induced gene silencing.
Hot pepper is one of the economically important crops in Asia. A large number of gene sequences, including expressed sequence tag (EST) and genomic sequences are publicly available. However, it is still a daunting task to determine gene function due to difficulties in genetic modification of a pepper plants. Here, we show the application of the virus-induced gene silencing (VIGS) repression for the study of 459 pepper ESTs selected as non-host pathogen-induced cell death responsive genes from pepper microarray experiments in Nicotiana benthamiana. Developmental abnormalities in N. benthamiana plants are observed in the 32 (7%) pepper ESTs-silenced plants. Aberrant morphological phenotypes largely comprised of three groups: stunted, abnormal leaf, and dead. In addition, by employing the combination of VIGS and Agrobacterium-mediated transient assays, we identified novel pepper ESTs that involved in Bax or INF1-mediated cell death responses. Silencing of seven pepper ESTs homologs suppressed Bax or INF1-induced cell death, five of which suppressed both cell death responses in N. benthamiana. The genes represented by these five ESTs encode putative proteins with functions in endoplasmic reticulum (ER) stress and lipid signaling. The genes represented by the other two pepper ESTs showing only Bax-mediated cell death inhibition encode a CCCH-type zinc finger protein containing an ankyrin-repeat domain and a probable calcium-binding protein, CML30-like. Taken together, we effectively isolated novel pepper clones that are involved in hypersensitive response (HR)-like cell death using VIGS, and identified silenced clones that have different responses to Bax and INF1 exposure, indicating separate signaling pathways for Bax- and INF1-mediated cell death.


Phase-II study of the new aza-anthracenedione, BBR 2778, in patients with relapsed aggressive non-Hodgkin's lymphomas.
BBR 2778 is a new aza-anthracenedione. Its activity against hematologic neoplasias in a mouse model is greater than that of doxorubicin or mitoxantrone. A phase-I study in patients with non-Hodgkin's lymphoma (NHL) showed that the drug has promising anti-tumor activity. Therefore, a phase-II study in patients with relapsed aggressive NHL was initiated. The primary objective was to determine the efficacy of 85 mg/m2 BBR 2278 for a q1w x3 treatment schedule (repeat day 29). Secondary objectives included the evaluation of response duration and safety in this open-label, non-randomized, multicenter trial. Patients with relapsed aggressive NHL according to the REAL-classification were included. Eight centers enrolled a total of 33 patients. The median age of these patients was 66 years (range 24-81). The majority of patients had diffuse large B-cell lymphoma (n=24) or mantle-cell lymphoma (n=7), pretreated with a median of 2 regimens. Confirmed responses included 5 complete and 4 partial remissions, with the period between the first appearance of response and any signs or symptoms of progression being up to 17+ months. The main toxicity was neutropenia. These results indicate that 85 mg/m2 BBR 2778 in a q1w x 3 schedule is active in elderly and pretreated patients with relapsed aggressive NHL and was generally well tolerated. Thus, we recommend further clinical evaluation of this new compound in phase-III studies for the treatment of NHL.


Long-term survival of inflatable penile prostheses: single surgical group experience with 2,384 first-time implants spanning two decades.
Long-term revision-free survival, greater than 10 years has never been reported for inflatable penile prostheses. We conducted a historical prospective study to estimate 10 and 15 years survival of first time (virgin) implantations in 2,384 patients with four different models. Evaluation of 10- and 15-year mechanical and overall revision-free survival of inflatable penile prostheses. Kaplan-Meier product limit method, and comparison using the log rank test, were used to estimate the 10- and 15-year revision-free survival. Data were obtained from medical records and patient interviews, entered into a computerized database, and analyzed by a third party. Information included implant type, date, revision history with date, and reason. Fourteen different inflatables were examined. Mentor Alpha 1, Mentor Alpha NB, AMS 700 CX, and AMS 700 Ultrex had usage for an extended period of time. Because of failure times being confounded as a result of prior implants, only virgin implants were examined. For the entire series, estimated 10-year revision-free survival for all reasons was 68.5% and the 15-year revision-free survival was 59.7%. Freedom from mechanical breakage at 10 years was 79.4%; 15 years was 71.2%. Recent mechanically enhanced models did even better. In 1992, Mentor Alpha added pump reinforcement to forestall mechanical breakage. This improved 10-year survival from 65.3% to 88.6% (P = 0.0001). In January 2001, AMS CX added a parylene coating to the cylinders that increased 3-year mechanical survival from 88.4 to 97.9% (P = 0.0002). This is the first report on long-term reliability of inflatable penile prostheses. We estimated 60% of these virgin implants would survive 15 or more years without revision or extraction. Newer enhanced models are currently available, and our tracking predicts even better long-term survival for these devices.


Autoimmune epilepsies.
To review the recent literature describing the detection and clinical importance of serum antibodies in patients with various epilepsies and other seizure-related disorders. Auto-antibodies to the NMDA, GABAB and AMPA receptors and to LGI1, CASPR2 and Contactin-2, components of the voltage-gated potassium channel complex, have been detected in the serum of patients with seizures. These antigenic targets are ion channels, receptors and accessory proteins important in both cellular homeostasis and governing the electrical activity of the brain. Antibodies to glutamic acid decarboxylase (GAD) have been found in patients with temporal lobe epilepsy. Antibodies to LGI1 have been described in around 90% of patients with the newly described epileptic syndrome of faciobrachial dystonic seizures. An increasing number of antibodies have been described in the epilepsies and other seizure-related disorders. Evidence of direct pathogenicity comes from the extracellular domain targeted by all of these antibodies (other than GAD) and the often dramatic clinical and serological response to immunotherapies, when antiepileptic drugs may be ineffective. Definitive proof as to the pathological relevance of these antibodies will be achieved in the generation of an animal model that demonstrates the clinical phenotype of these antibody-mediated disorders.


The relationship between cognitive reserve and functional ability is mediated by executive functioning in older adults.
It has been noted in the literature that cognitive reserve (CR) predicts future functional ability (FA), but the association between CR and current FA is rather limited. This investigation aimed to explicate this relationship, and hypothesized it would be mediated by executive functioning (EF). To best understand the relationship between CR and FA, we recruited and tested independent community-dwelling older adults (OAs). Bivariate correlations and hierarchical regressions were completed to determine the association between CR and FA. Both individual CR measures and a composite CR score were used. Mediation analyses were completed to examine our hypothesis that EF would mediate the CR and FA relationship. All measures of CR were positively related to and predictive of FA. Although the highest zero-order correlation across the independent CR proxies was between income and FA (r = .417), education accounted for the greatest amount of variance in FA, 8.3% after controlling for age and Mini-Mental State Examination performance. Furthermore, the CR composite had a higher correlation (r = .447) and accounted for more variance than any of the independent proxies. Complete mediation was found between a CR composite and FA via an internally consistent D-KEFS composite score (Cronbach's α = .795). This suggests that as CR increases so does EF, which in turn improves FA. Thus, future investigations could determine the effect on FA in OAs by improving EF.


Ecophysiological models for global invaders: Is Europe a big playground for the African clawed frog?
One principle threat prompting the worldwide decline of amphibians is the introduction of nonindigenous amphibians. The African Clawed Frog, Xenopus laevis, is now one of the widest distributed amphibians occurring on four continents with ongoing range expansion including large parts of Europe. Species distribution models (SDMs) are essential tools to predict the invasive risk of these species. Previous efforts have focused on correlative approaches but these can be vulnerable to extrapolation errors when projecting species' distributions in nonnative ranges. Recent developments emphasise more robust process-based models, which use physiological data like critical thermal limits and performance, or hybrid models using both approaches. Previous correlative SDMs predict different patterns in the potential future distribution of X. laevis in Europe, but it is likely that these models do not assess its full invasive potential. Based on physiological performance trials, we calculate size and temperature-dependent response surfaces, which are scaled to geographic performance layers matching the critical thermal limits. We then use these ecophysiological performance layers in a standard correlative SDM framework to predict the potential distribution in southern Africa and Europe. Physiological performance traits (standard metabolic rate and endurance time of adult frogs) are the main drivers for the predicted distribution, while the locomotor performance (maximum velocity and distance moved in 200 ms) of adults and tadpoles have low contributions.


The Rohingya in Cox's Bazar: When the Stateless Seek Refuge.
The Rohingya people of Myanmar have been subject to human rights violations through government-sponsored discrimination and violence. Since August 2017, an intensified assault by Myanmar authorities has resulted in a rapid increase of Rohingya pouring into Bangladesh, and the expansion of refugee settlements in the district of Cox's Bazar has strained humanitarian and government relief efforts. Assessing Rohingya and host community needs is critical for prioritizing resource allocations and for documenting the rights violations suffered by Rohingya refugees. From March 15 to 18, 2018, we conducted a rapid needs assessment of recently arrived Rohingya and host community households. We collected data on demographics, mortality, education, livelihoods, access to food and water, vaccination, and health care. Among other things, our survey found high levels of mortality among young Rohingya men, alarmingly low levels of vaccination among children, poor literacy, and rising poverty. Denied formal refugee status, the Rohingya cannot access due protections and find themselves in a state of insecurity in which they are unsure of their future and unable to formally seek work or send their children to school. While the government of Bangladesh explores the options of repatriation, relocation, and third-country resettlement for these refugees, it is important to ensure that they are not denied a life of dignity.


Regulation of bile secretion by sympathetic nerves in perfused rat liver.
Although the biliary system is innervated by the autonomic nervous system, little is known about the regulation of bile secretion by hepatic nerves. In rat liver perfused in situ with constant pressure and erythrocyte-free medium, hepatic nerves were electrically stimulated (20 V, 20 Hz, 2 ms) by a platinum electrode placed around the hepatic artery and portal vein. Nerve stimulation caused a decrease in bile flow, bile acid secretion, and portal flow. The nerve effects on bile secretion were mediated via alpha 1-receptors. In this system, artificial reduction of perfusion flow by 30% led to a similar decrease of bile flow. In perfusion systems with constant flow and erythrocyte-free medium or with constant pressure and erythrocyte-containing medium, the nerve effects were reproduced despite the altered hemodynamics and the increased oxygen supply. In addition, partial inhibition by sodium nitroprusside of the nerve-induced reduction of portal flow had little effect on the reduction in bile secretion. In conclusion, a direct effect on bile formation was suggested. Yet an additional role of a vascular-mediated effect could not definitively be excluded. With the use of inhibitors of prostanoid synthesis the nerve effects on bile secretion were markedly reduced, suggesting a mediating or modulating role of prostanoids.


Association between full service and fast food restaurant density, dietary intake and overweight/obesity among adults in Delhi, India.
The food environment has been implicated as an underlying contributor to the global obesity epidemic. However, few studies have evaluated the relationship between the food environment, dietary intake, and overweight/obesity in low- and middle-income countries (LMICs). The aim of this study was to assess the association of full service and fast food restaurant density with dietary intake and overweight/obesity in Delhi, India. Data are from a cross-sectional, population-based study conducted in Delhi. Using multilevel cluster random sampling, 5364 participants were selected from 134 census enumeration blocks (CEBs). Geographic information system data were available for 131 CEBs (n = 5264) from a field survey conducted using hand-held global positioning system devices. The number of full service and fast food restaurants within a 1-km buffer of CEBs was recorded by trained staff using ArcGIS software, and participants were assigned to tertiles of full service and fast food restaurant density based on their resident CEB. Height and weight were measured using standardized procedures and overweight/obesity was defined as a BMI ≥25 kg/m2. The most common full service and fast food restaurants were Indian savory restaurants (57.2%) and Indian sweet shops (25.8%). Only 14.1% of full service and fast food restaurants were Western style. After adjustment for age, household income, education, and tobacco and alcohol use, participants in the highest tertile of full service and fast food restaurant density were less likely to consume fruit and more likely to consume refined grains compared to participants in the lowest tertile (both p < 0.05). In unadjusted logistic regression models, participants in the highest versus lowest tertile of full service and fast food restaurant density were significantly more likely to be overweight/obese: odds ratio (95% confidence interval), 1.44 (1.24, 1.67). After adjustment for age, household income, and education, the effect was attenuated: 1.08 (0.92, 1.26). Results were consistent with further adjustment for tobacco and alcohol use, moderate physical activity, and owning a bicycle or motorized vehicle. Most full service and fast food restaurants were Indian, suggesting that the nutrition transition in this megacity may be better characterized by the large number of unhealthy Indian food outlets rather than the Western food outlets. Full service and fast food restaurant density in the residence area of adults in Delhi, India, was associated with poor dietary intake. It was also positively associated with overweight/obesity, but this was largely explained by socioeconomic status. Further research is needed exploring these associations prospectively and in other LMICs.


Expression of monocarboxylate transporter (MCT)-4 in colorectal cancer and its role: MCT4 contributes to the growth of colorectal cancer with vascular endothelial growth factor.
In tumor cells, monocarboxylate transporter (MCT)-4 regulates the excretion of lactate produced by glycolysis from the cell. MCT4 has also been reported to be involved in tumor growth and infiltration. Similarly, vascular endothelial growth factor (VEGF) is known to be involved in the growth, infiltration, and metastasis of tumors. In this study, we clinically evaluated the relationship between MCT4 and VEGF in colorectal cancer. A prospective study was conducted in 210 patients with colorectal cancer who underwent surgical treatment. The clinicopathological data were correlated with the expression of MCT4 and VEGF obtained from immunohistochemical analysis. MCT4 and VEGF were expressed in tumors of 102 (49%) and 129 (61%) patients, respectively. A maximum tumor diameter of 45 mm or more (p<0.0001) and a tumor invasion depth of T1 or less (p<0.0119) were factors independently correlated with the expression of MCT4 and VEGF, respectively. The tumor size was significantly smaller (p=0.0031), and the disease was significantly less advanced (p=0.0017), in MCT4-negative/VEGF-positive than MCT4-positive/VEGF-negative cases. We suspect that in colorectal cancer, VEGF is involved in the early stages of tumor growth and MCT4 expression appears as the tumor enlarges and contributes to its further infiltration and growth.


Terrabacter lapilli sp. nov., an actinomycete isolated from stone.
A novel actinomycete, designated strain LR-26T, was isolated from a small stone collected from an agricultural field in Jeju, Republic of Korea. Cells of the organism were strictly aerobic, Gram-positive, non-motile, short rods. Colonies were bright yellow, circular, smooth and translucent. The organism was characterized chemotaxonomically as having ll-diaminopimelic acid in the cell wall, MK-8(H4) as major menaquinone, a polar lipid profile including diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol and unknown phospholipids, iso-C15 : 0 as the predominant fatty acid and a DNA G+C content of 72.6 mol%. Comparative 16S rRNA gene sequence analysis showed that the organism was related to the genera Intrasporangium, Terracoccus and Terrabacter within the family Intrasporangiaceae. The closest phylogenetic relatives of strain LR-26T were the type strains of Terrabacter terrae (99.4 % 16S rRNA gene sequence similarity), Terrabacter aerolatus (99.3 %) and Terrabacter tumescens (99.3 %). DNA-DNA hybridization experiments showed that strain LR-26T shared low levels of DNA-DNA relatedness with Terrabacter terrae LMG 22921T (17.6 and 22.8 % from reciprocal experiments) and with Terrabacter tumescens IMSNU 21313T (27.6 and 34.9 %). The phenotypic data and low levels of DNA-DNA relatedness readily distinguished strain LR-26T from the type strains of recognized species of the genus Terrabacter, and showed that it therefore represents a novel species. The name Terrabacter lapilli sp. nov. is proposed for this novel actinomycete. The type strain is LR-26T (=JBRI 2002T =KCTC 19199T =DSM 18583T).


The significance of ONSD, ONSD/ETD ratio, and other neuroimaging parameters in idiopathic intracranial hypertension.
Background: The measurement of the optic nerve sheath diameter (ONSD) has been suggested to be used in the evaluation of intracranial pressure of several etiologies. However, its potential utility in the clinical evaluation of patients with idiopathic intracranial hypertension (IIH) needs to be clarified.Methods: We recruited all the IIH patients who had been admitted to our neurology clinics and had a cranial MRI before lumbar puncture investigation. A control group of patients with migraine was also included. Studies were reviewed blindly by a radiologist, and ONSD and ONSD/ eyeball transverse diameter (ETD) for both eyes were measured.Results: Ultimately, we have enrolled 50 patients with IIH and 53 migraineurs. The right ONSD values were higher in the IIH group (p = 0.024) whereas the values of ONSD/ETD were found to be both higher in the IIH group (right: p = 0.006, left: p = 0.043). The ROC curve demonstrated an area under the curve of 0.620 (95% CI = 0.508 to 0.731) for ONSD, and it was 0.642 for ONSD/ETD. Using a cut-off of 6.3 mm, ONSD had the following performance characteristics: sensitivity 18%, specificity 81%.Conclusions: The ONSD and ONSD/ETD values may be utilizable in the evaluation processes of IIH patients; however, they do not solely reach sufficient discriminative accuracy. The potential significance of these parameters in rather monitoring the IIH patients may constitute a strictly crucial topic of interest for future research.


Maternal, neonatal, and placental features associated with diffuse chorioamniotic hemosiderosis, with special reference to neonatal morbidity and mortality.
Our purpose was to examine the significance of diffuse chorioamniotic hemosiderosis (DCH) on neonatal morbidity and mortality. Using data from a retrospective case-control study, we analyzed 46 singleton placentas with DCH from infants who were delivered and/or admitted to the neonatal intensive care unit of Kanagawa Children's Medical Center during 1987-2001 and 92 control placentas without DCH from infants of comparable gestational age, birth weight, and duration. Mean and standard deviation of gestational age and infants' birth weight at delivery from the DCH group were 27 +/- 3 weeks and 939 +/- 342 g, respectively. Macroscopically, the placentas with DCH were more likely to show old peripheral blood clots (46% in the DCH group vs 8% in control group), subchorionic hematoma (20% vs 1%), and circumvallation (13% vs 1%). Histologically, amniotic necrosis was significantly more frequent in the DCH group (63% vs 24%). Of the obstetric factors, incidence of recurrent episodes of vaginal bleeding (70% vs 11%), oligohydramnios (59% vs 8%), and chronic abruption-oligohydramnios sequence (57% vs 5%) were significantly higher in the DCH group. Of the neonatal factors, persistent pulmonary hypertension of the newborn (29% vs 8%) and dry lung and/or pulmonary hypoplasia (20% vs 4%) were more common. However, respiratory distress syndrome was rare (15% vs 45%) in the DCH group. Neonatal death including stillbirth was increased in the DCH group but was not significant (24% vs 15%). Of infants who survived beyond day 28, chronic lung disease (CLD) was more frequent in the DCH group (51% vs 22%). The association of DCH, especially accompanied by amniotic necrosis, with CLD was still evident using likelihood ratio test. DCH is closely associated with preterm delivery, pulmonary hypertension of the newborn, and dry lung syndrome and is a significant risk factor for CLD.


[Present views of the etiology and pathogenesis of rapidly progressive periodontitis].
In modern dentistry, the problem of occurrence of atypical forms of periodontal inflammatory diseases, namely rapidly progressive periodontitis (RPP), has assumed a particular significance due the increasing incidence of this pathology. The paper considers the main lines of the etiology and pathogenesis of this disease. By taking into account the current data available in the literature, it may be assumed that the development ofa systemic inflammatory response, destabilization of cellular membranes, followed by the development of endothelial dysfunction and progressing microcirculatory disorders, are one of the mechanisms of the pathogenesis of RPP.


Ethnic Differences in Informal Caregiving After Stroke.
Informal (unpaid) caregiving usually provided by family is important poststroke. We studied whether the prevalence of informal caregiving after stroke differs between Mexican Americans (MAs) and non-Hispanic Whites (NHWs). Between October 2014 and December 2018, participants in the BASIC (Brain Attack Surveillance in Corpus Christi) project in Nueces County, Texas, were interviewed 90 days after stroke to determine which activities of daily living they required help with and whether family provided informal caregiving. Ethnic differences between MAs and NHWs were determined by logistic regression. The logistic models were stratified by formal (paid) care status. Odds ratios (95% CIs) are reported with NHW as the referent group. Fisher exact tests were used to assess the association of ethnicity with relationship of caregiver and with individual activities of daily living. Eight hundred thirty-one patients answered the caregiving questions. Of these, 242 (29%) received family caregiving (33% of MAs and 23% of NHWs), and 142 (17%) received paid caregiving (21% of MAs and 10% of NHWs). There were no ethnic differences in stroke severity. In logistic regression analyses, among those without formal, paid care, MAs were more likely to have informal caregiving (odds ratio, 1.75 [95% CI, 1.12-2.73]) adjusted for age, National Institutes of Health Stroke Scale, prestroke modified Rankin Scale, and insurance. No ethnic differences in informal care were found among those who had formal care. There were no differences between ethnic groups in which family members provided the informal care. MAs were more likely to require help compared with NHWs for walking (P<0.0001), bathing (P<0.0001), hygiene (P=0.0012), eating (P=0.0004), dressing (P<0.0001), ambulating (P=0.0304), and toileting (P=0.0003). MAs required more help poststroke than NHWs for assistance with activities of daily living. MAs received more help for activities of daily living through informal, unpaid caregiving than NHWs if they were not also receiving formal, paid care. Efforts to help minority and low-resource populations provide stroke care are needed.


Attitudes of Asian patients in Birmingham to general practitioner services.
Attitudes of Asian patients to the delivery of primary health care in two Birmingham general practices were investigated by questionnaires administered by an Asian ethnic minorities worker who spoke dialects appropriate to the population under investigation. One practice was staffed by Asian doctors the other by British doctors. The responses to the questionnaires were analysed with reference to religion - Sikh, Hindu and Muslim and to the two practices. Choice of doctor appears to be determined more by the proximity of the patient's home to the practice premises than by ethnic considerations. Reported failures to meet the special needs of Asian patients were those inherent in the difficulties of British general practice and were not peculiar to Asian patients. The need for help from an interpreter did not seem to be important.


Brain iron deficiency and excess; cognitive impairment and neurodegeneration with involvement of striatum and hippocampus.
While iron deficiency is not perceived as a life threatening disorder, it is the most prevalent nutritional abnormality in the world, and a better understanding of modes and sites of action, can help devise better treatment programs for those who suffer from it. Nowhere is this more important than in infants and children that make up the bulk of iron deficiency in society. Although the effects of iron deficiency have been extensively studied in systemic organs, until very recently little attention was paid to its effects on brain function. The studies of Oski at Johns Hopkin Medical School in 1974, demonstrating the impairment of learning in young school children with iron deficiency, prompted us to study its relevance to brain biochemistry and function in an animal model of iron deficiency. Indeed, rats made iron deficient have lowered brain iron and impaired behaviours including learning. This can become irreversible especially in newborns, even after long-term iron supplementation. We have shown that in this condition it is the brain striatal dopaminergic-opiate system which becomes defective, resulting in alterations in circadian behaviours, cognitive impairment and neurochemical changes closely associated with them. More recently we have extended these studies and have established that cognitive impairment may be closely associated with neuroanatomical damage and zinc metabolism in the hippocampus due to iron deficiency, and which may result from abnormal cholinergic function. The hippocampus is the focus of many studies today, since this brain structure has high zinc concentration and is highly involved in many forms of cognitive deficits as a consequence of cholinergic deficiency and has achieved prominence because of dementia in ageing and Alzheimer's disease. Thus, it is now apparent that cognitive impairment may not be attributed to a single neurotransmitter, but rather, alterations and interactions of several systems in different brain regions. In animal models of iron deficiency it is apparent that dopaminergic interaction with the opiate system and cholinergic neurotransmission may be defective.


Oxygen activation and electron transfer in flavocytochrome P450 BM3.
In flavocytochrome P450 BM3, there is a conserved phenylalanine residue at position 393 (Phe393), close to Cys400, the thiolate ligand to the heme. Substitution of Phe393 by Ala, His, Tyr, and Trp has allowed us to modulate the reduction potential of the heme, while retaining the structural integrity of the enzyme's active site. Substrate binding triggers electron transfer in P450 BM3 by inducing a shift from a low- to high-spin ferric heme and a 140 mV increase in the heme reduction potential. Kinetic analysis of the mutants indicated that the spin-state shift alone accelerates the rate of heme reduction (the rate determining step for overall catalysis) by 200-fold and that the concomitant shift in reduction potential is only responsible for a modest 2-fold rate enhancement. The second step in the P450 catalytic cycle involves binding of dioxygen to the ferrous heme. The stabilities of the oxy-ferrous complexes in the mutant enzymes were also analyzed using stopped-flow kinetics. These were found to be surprisingly stable, decaying to superoxide and ferric heme at rates of 0.01-0.5 s(-)(1). The stability of the oxy-ferrous complexes was greater for mutants with higher reduction potentials, which had lower catalytic turnover rates but faster heme reduction rates. The catalytic rate-determining step of these enzymes can no longer be the initial heme reduction event but is likely to be either reduction of the stabilized oxy-ferrous complex, i.e., the second flavin to heme electron transfer or a subsequent protonation event. Modulating the reduction potential of P450 BM3 appears to tune the two steps in opposite directions; the potential of the wild-type enzyme appears to be optimized to maximize the overall rate of turnover. The dependence of the visible absorption spectrum of the oxy-ferrous complex on the heme reduction potential is also discussed.


Anemia in young patients with ischaemic stroke.
To investigate the association of anemia on admission with ischaemic stroke (IS), stroke severity and early functional outcome in patients with cervical artery dissection (CeAD) or with IS of other causes (non-CeAD-IS patients). The study sample comprised all patients from the Cervical Artery Dissection and Ischaemic Stroke Patients (CADISP) study without pre-existing disability and with documentation of stroke severity and hemoglobin (Hb) concentration on admission. Anemia was classified as mild (Hb < 12 g/dl in women and Hb < 13 g/dl in men) or moderate to severe (Hb < 10 g/dl in women and Hb < 11 g/dl in men). Stroke severity on admission was assessed with the National Institutes of Health Stroke Scale (NIHSS). Outcome after 3 months was assessed with the modified Rankin Scale (mRS-3mo). Unfavorable outcome was defined as mRS-3mo ≥ 3. Amongst 1206 study patients (691 CeAD and 515 non-CeAD), 87 (7.2%) had anemia, which was moderate to severe in 18 (1.5%) patients. Anemia was associated with female sex in both study samples, but no further associations with risk factors or comorbidities were observed. In CeAD patients, anemia was associated with occurrence of stroke (P = 0.042). In both study samples, anemic patients had more severe strokes (CeAD, P = 0.023; non-CeAD, P = 0.005). Functional outcome was not associated with anemia in general, but moderate to severe anemia was significantly associated with unfavorable outcome (P = 0.004). Anemia on admission was associated with stroke in CeAD patients and with more severe strokes in both study samples. Moderate to severe anemia may predict unfavorable outcome.


Ultrasonography reinvents the originally described technique for ganglion impar neurolysis in perianal cancer pain.
Visceral pain in the perineal area associated with malignancies may be effectively treated with neurolysis of the ganglion impar. Since the first description of the technique of accessing the ganglion impar through anococcygeal ligament, many techniques for ganglion impar block have been described. We present a patient diagnosed with carcinoma of the anal canal who was successfully given ultrasound-guided ganglion impar block using a Chiba needle inserted through the anococcygeal ligament. In summary, ultrasound-guided ganglion impar neurolysis is a fast, safe, and cost-effective method, which can be used as a first-line pain relief intervention for good quality of life in patients with perianal cancers.


[Mechanistic study of monoamine oxidase: significance for MAO A and MAO B in situ].
MAO A and MAO B follow the same chemical mechanism to oxidise primary, secondary, and tertiary amines, but they are distinguished by differences in their substrate and inhibitor specificities and in their kinetic behaviour. Studies on the purified enzymes show that monoamine oxidases are unusual enzymes because certain amine substrates accelerate the oxidative half-reaction (much more in A than in B) and because substrate binding induces an enormous positive shift in the redox potential of the flavin. The molecular basis of these features is still unknown, as is the structure of the active site, information necessary for national drug design. This article reviews the biochemistry of MAO in general and speculates about what the kinetic and thermodynamic properties observed in the isolated enzymes mean for the catalytic expression of their amine oxidase activities in vivo. Specific and distinct physiological roles for MAO A and MAO B are probable because they are expressed in different proportions in different cell types and their expression varies in development and ageing. Molecular localization techniques can now be used to measure the levels of MAO in specific cell types rather than a region of mixed cells. When this information is combined with the kinetic constants, it will be possible to construct numerical models to predict the metabolism of a given amine by a particular cell which should help in understanding the role of amines in development and perhaps also the role of the endogenous inhibitors in altering levels of bioactive amines.


Abdominal wall cellulitis in the morbidly obese.
Currently, almost two-thirds of the US population is either overweight or obese. In addition to non-infectious complications, obesity predisposes to infections, including lower extremity cellulitis. Although cases of abdominal wall cellulitis in the morbidly obese occur, to date there has been no formal address of this syndrome in the literature. We therefore reviewed our clinical experience of abdominal wall cellulitis complicating morbid obesity. A retrospective database search was performed to identify patients with both cellulitis and morbid obesity who were seen at the Mayo Clinic between January 1998 and August 2003. Clinical and microbiologic data were collected for these patients. Of the 260 cases of cellulitis identified, 24 (9.2%) had morbid obesity and abdominal wall cellulitis. The mean age of the 24 patients was 47 (range 22-70) y and over two-thirds of them were females. Their mean body mass index (BMI) was 62.3 (range 39.6-108.6). 17 (70.8%) had a remote history of abdominal surgery. 16 patients required 23 hospitalizations. Five patients developed cellulitis complications and 7 (29.1%) patients had recurrent bouts of cellulitis during the study period. Abdominal wall cellulitis is a unique infectious complication in patients with morbid obesity. Further study is needed to better define the pathogenesis of this illness to develop strategies in treatment and prevention.


Replacement of proteoglycans in embryonic chick cartilage in organ culture after treatment with testicular hyaluronidase.
Explants of cartilage from tibiae of 11-12 days chick embryos were grown in organ culture. To one group hyaluronidase was added to the medium during the first 2 days of culture; the treated tissue was then cultured in medium without enzyme for a further 4 days. Control explants grown in hyaluronidase-free medium for 6 days grew rapidly in size and the total hexosamine content more than doubled during this time. After exposure to hyaluronidase, much of the hexosamine was lost from treated cartilage and appeared in the culture medium, but it was mostly replaced in the tissue during the subsequent recovery period. Analysis of cartilage and medium showed that net synthesis of hexosamine increased greatly in treated cartilage. The proteoglycans were extracted by two procedures from control and treated cartilage after 2, 4 and 6 days in culture. The hydrodynamic sizes of the purified proteoglycans were compared by gel chromatography and the composition of the gel-chromatographic fractions was determined. The proteoglycans from controls did not change during culture, but after exposure to hyaluronidase the proteoglycans from treated cartilage were of much smaller size and lower chondroitin sulphate content. During recovery, even though new proteoglycans were formed, they were nevertheless of smaller size and lower chondroitin sulphate content than control proteoglycans. They gradually became more like control proteoglycans during recovery from treatment, but even after 4 days they were not yet the same. After 2 days of treatment with the enzyme, the chondroitin sulphate in the cartilage was of shorter chain length than in controls but during recovery after 4 and 6 days in culture, the chain lengths in control and treated cartilage were similar. It is concluded that the proteoglycans formed in embryo cartilage in response to their depletion by enzyme treatment contained fewer chondroitin sulphate chains attached to the protein moiety of proteoglycans. This may have resulted from a failure under stress to glycosylate the protein moiety to the usual extent; alternatively the synthesis of normal proteoglycans of low chondroitin sulphate content may have increased, thus changing the proteoglycan population.


Baseline differences and trajectories of change for deceased, placed, and community residing Alzheimer disease patients.
This study identifies predictors of placement or death in a large ethnically/racially diverse sample of moderately impaired Alzheimer disease patients residing in the community. Patients and caregivers were followed for 18 months with 4 assessments at 6-month intervals. Multinomial regression was used to identify caregiver and patient baseline characteristics and changes over time as predictors of patient placement in a long-term care facility (n=180), patient death (not preceded by placement, n=187), or remaining in the community at home (n=583). Our findings reveal important differences between death and placement when compared with continued home care. Both death and placement are significantly associated with increased activities of daily living limitations (Exp(B)=1.285, P=0.017; Exp(B)=0.1.202, P=0.038, for death and placement, compared with home care, respectively), having a nonspouse caregiver [Exp(B)=0.325, P=0.026; Exp(B)=0.386, P=0.050, for death and placement, respectively], and being a male patient [Exp(B)=0.367, P=0.003; Exp(B)=0.439, P=0.016, for death and placement, respectively]. Death and placement differ with respect to health service use, race, and group assignment. Whites are more likely to be placed rather than remain at home when compared with African American [Ex(B)=0.520, P=0.028] or Hispanic [Exp(B)=0.338, P<0.005] patients, whereas being assigned to the control condition as opposed to active treatment [Exp(B)=0.515, P=0.008], having a male caregiver [Exp(B)=0.482, P=0.043], and increasing patient health service use [Exp(B)=1.105, P=0.015] are associated with increased mortality. Placed and deceased patients are further differentiated from each other by the fact that caregivers of placed patients report an increase in being bothered by memory problems when compared with caregivers of deceased patients [Exp(B)=0.577, P=0.006]. Patients who are placed, died, or remain at home have unique trajectories, which vary as a function of the reference group used for comparison. Increasing bother with memory problems is uniquely associated with placement relative to death while increasing health service use in the form of physician contacts and nurses visits is uniquely associated with death among community residing Alzheimer disease patients.


Histone gene replacement reveals a post-transcriptional role for H3K36 in maintaining metazoan transcriptome fidelity.
Histone H3 lysine 36 methylation (H3K36me) is thought to participate in a host of co-transcriptional regulatory events. To study the function of this residue independent from the enzymes that modify it, we used a 'histone replacement' system in Drosophila to generate a non-modifiable H3K36 lysine-to-arginine (H3K36R) mutant. We observed global dysregulation of mRNA levels in H3K36R animals that correlates with the incidence of H3K36me3. Similar to previous studies, we found that mutation of H3K36 also resulted in H4 hyperacetylation. However, neither cryptic transcription initiation, nor alternative pre-mRNA splicing, contributed to the observed changes in expression, in contrast with previously reported roles for H3K36me. Interestingly, knockdown of the RNA surveillance nuclease, Xrn1, and members of the CCR4-Not deadenylase complex, restored mRNA levels for a class of downregulated, H3K36me3-rich genes. We propose a post-transcriptional role for modification of replication-dependent H3K36 in the control of metazoan gene expression.


Identifying patients at high risk of emergency hospital admissions: a logistic regression analysis.
To use routine data to identify patients at high risk of future emergency hospital admissions. Descriptive analysis of inpatient hospital episode statistics. Predictive model developed using multiple logistic regression. National Health Service hospital trusts in England. All patients with an emergency admission to an NHS hospital between 1 April 2000 and 31 March 2001. 'High-impact users' were defined as patients who had at least one emergency inpatient admission and who then went on to have at least two further emergency hospital admissions in the 12 months following the start date of that index admission. 2,895,234 patients were admitted as emergencies in 2000/2001, of whom 147,725 (5.1%) did not survive their first spell. Of the 2,747,509 surviving patients, 269,686 (9.8%) subsequently had at least two or more emergency admissions within 365 days of the index date of admission. A further 236,779 (8.6%) died during this period. Risk factors for becoming a high-impact user included the number of emergencies in the 36 months before index spell, comorbidity, age, an admission for an ambulatory care sensitive condition, ethnicity, area-level socioeconomic data, local admission rates, the number of episodes in the index spell, sex and the source of admission. The predictive model based on all emergency admissions produced a receiver operating characteristic curve score of 0.72. Routine hospital episode statistics can be used to identify patients who are at high risk of suffering future multiple emergency hospital admissions. The potential cost savings in preventing a proportion of these subsequent admissions need to be compared with the costs of case management of these patients.


Anaplastic thyroid cancers harbor novel oncogenic mutations of the ALK gene.
Thyroid cancer is the most common endocrine cancer, and targeted approaches to treat it pose considerable interest. In this study, we report the discovery of ALK gene mutations in thyroid cancer that may rationalize clinical evaluation of anaplastic lymphoma kinase (ALK) inhibitors in this setting. In undifferentiated anaplastic thyroid cancer (ATC), we identified two novel point mutations, C3592T and G3602A, in exon 23 of the ALK gene, with a prevalence of 11.11%, but found no mutations in the matched normal tissues or in well-differentiated thyroid cancers. These two mutations, resulting in L1198F and G1201E amino acid changes, respectively, both reside within the ALK tyrosine kinase domain where they dramatically increased tyrosine kinase activities. Similarly, these mutations heightened the ability of ALK to activate the phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein (MAP) kinase pathways in established mouse cells. Further investigations showed that these two ALK mutants strongly promoted cell focus formation, anchorage-independent growth, and cell invasion. Similar oncogenic properties were observed in the neuroblastoma-associated ALK mutants K1062M and F1174L but not in wild-type ALK. Overall, our results reveal two novel gain-of-function mutations of ALK in certain ATCs, and they suggest efforts to clinically evaluate the use of ALK kinase inhibitors to treat patients who harbor ATCs with these mutations.


[Cemented total hip arthroplasty in Germany--an update].
The results of a national survey from 1998 had shown at the time that only around 10 % of orthopaedic surgeons in Germany had strictly implemented modern cementing techniques in total hip arthroplasty (THA). The same study was repeated 5 years later to evaluate the current situation and to determine whether modern cementing techniques have become more popular. A detailed, slightly modified questionnaire regarding cement and bone preparation, cementing techniques on acetabulum and femur, and implant types was sent to 572 German orthopaedic and trauma hospitals, as well as to visiting surgeons with an interest in THA. In total, 293 questionnaires were available for evaluation and statistical analysis. Palacos bone cement remained the most widely used cement (> 90 %). The mixing times given varied significantly. Vacuum mixing systems had become more popular (67.9 %). In the femur 81.8 % of the surgeons attempted to preserve cancellous bone and 57.2 % used pulsatile lavage (jet-lavage). Retrograde cement application via a cement gun was done in 71.1 %. Cement restrictors were used in more than 95 %. Only two-thirds of the surgeons implemented sustained cement pressurisation and preferred a cement mantle thickness > 2mm (64 %). Only 16.9 % made multiple small acetabular keyholes and 48.6 % used jet-lavage. In 73.1 % no cement gun was used and in 68.3 % the cement was applied at high viscosity. Manual cement pressurisation was done in 58.1 %. The Muller straight stem device remained the most popular implant. For only 5 of the over 50 stem designs implanted have long-term results been published as yet. Only 10.6 % of surgeons/centres performed > 20 and almost 50 % implanted > 100 cemented THAs/year. The results of this survey demonstrated that, in comparison to 1998, the current state of cemented THA, in particular cementing technique has significantly improved. Future emphasis should be on continued surgeon education and training, as the operative, i. e., cementing techniques are of utmost importance for long-term success.


Immune-Endocrine Links to Gregariousness in Wild House Mice.
Social interactions are critically important for survival and impact overall-health, but also impose costs on animals, such as exposure to contagious agents. The immune system can play a critical role in modulating social behavior when animals are sick, as has been demonstrated within the context of "sickness behaviors." Can immune molecules affect or be affected by social interactions even when animals are not sick, therefore serving a role in mediating pathogen exposure? We tested whether markers of immune function in both the blood and the brain are associated with gregariousness, quantified as number of animals interacted with per day. To do this, we used remote tracking of social interactions of a wild population of house mice (Mus musculus domesticus) to categorize animals in terms of gregariousness. Blood, hair, brain and other tissue samples from animals with extreme gregariousness phenotypes were collected. We then tested whether the levels of three important cytokines (TNF-α, IFN-γ and IL-1β) in the serum, cortex and hypothalamus of these animals could be explained by the gregariousness phenotype and/or sex of the mice. Using the hair as a long-term quantification of steroid hormones, we also tested whether corticosterone, progesterone and testosterone differed by social phenotype. We found main effects of gregariousness and sex on the serum levels of TNF-α, but not on IFN-γ or IL-1β. Brain gene expression levels were not different between phenotypes. All hair steroids tended to be elevated in animals of high gregariousness phenotype, independent of sex. In sum, elements of the immune system may be associated with gregariousness, even outside of major disease events. These results extend our knowledge of the role that immune signals have in contributing to the regulation of social behaviors outside periods of illness.


Eating competence of elderly Spanish adults is associated with a healthy diet and a favorable cardiovascular disease risk profile.
Eating competence (EC), a bio-psychosocial model for intrapersonal approaches to eating and food-related behaviors, is associated with less weight dissatisfaction, lower BMI, and increased HDL-cholesterol in small U.S. studies, but its relationship to nutrient quality and overall cardiovascular risk have not been examined. Prevención con Dieta Mediterránea (PREDIMED) is a 5-y controlled clinical trial evaluating Mediterranean diet efficacy on the primary prevention of cardiovascular diseases (CVD) in Spain. In a cross-sectional study, 638 PREDIMED participants (62% women, mean age 67 y) well phenotyped for cardiovascular risk factors were assessed for food intake and EC using validated questionnaires. Overall, 45.6% were eating-competent. EC was associated with being male and energy intake (P < 0.01). After gender and energy adjustment, participants with EC compared with those without showed higher fruit intake and greater adherence to the Mediterranean diet (P < 0.05) and tended to consume more fish (P = 0.076) and fewer dairy products (P = 0.054). EC participants tended to have a lower BMI (P = 0.057) and had a lower fasting blood glucose concentration and serum LDL-:HDL-cholesterol ratio (P < 0.05) and a higher HDL-cholesterol concentration (P = 0.025) after gender adjustment. EC participants had lower odds ratios (OR) of having a blood glucose concentration >5.6 mmol/L (0.71; 95% CI 0.51-0.98) and HDL-cholesterol <1.0 mmol/L (0.70; 95% CI 0.68-1.00). The OR of actively smoking, being obese, or having a serum LDL-cholesterol concentration > or =3.4 mmol/L were <1.0, but the 95% CI included the 1.0 (P > 0.1). Our findings support further examination of EC as a strategy for enhancing diet quality and CVD prevention.


Chromosomal instability in amniocytes from fetuses of mothers who smoke.
Tobacco increases the risk of systemic diseases, and it has adverse effects on pregnancy. However, only indirect data have been published on a possible genotoxic effect on pregnancy in humans. To determine whether maternal smoking has a genotoxic effect on amniotic cells, expressed as an increased chromosomal instability, and to analyze whether any chromosomal regions are especially affected by exposure to tobacco. In this prospective study, amniocytes were obtained by routine amniocentesis for prenatal diagnosis from 25 controls and 25 women who smoke (> or =10 cigarettes/d for > or =10 years), who were asked to fill out a smoking questionnaire concerning their smoking habits. Chromosomal instability was analyzed in blinded fashion by 2 independent observers in routine chromosome spreads. Breakpoints implicated in chromosomal abnormalities were identified by G-banding. Association between maternal smoking and increased chromosomal instability in amniotic fluid cells, expressed as chromosomal lesions (gaps and breaks) and structural chromosomal abnormalities. Comparison of cytogenetic data between smokers and nonsmokers (controls) showed important differences for the proportion of structural chromosomal abnormalities (smokers: 12.1% [96/793]; controls: 3.5% [26/752]; P = .002) and to a lesser degree for the proportion of metaphases with chromosomal instability (smokers: 10.5% [262/2492]; controls: 8.0% [210/2637]; P = .04), and for the proportion of chromosomal lesions (smokers: 15.7% [391/2492]; controls: 10.1% [267/2637]; P = .045). Statistical analysis of the 689 breakpoints detected showed that band 11q23, which is a band commonly implicated in hematopoietic malignancies, was the chromosomal region most affected by tobacco. Our findings show that smoking 10 or more cigarettes per day for at least 10 years and during pregnancy is associated with increased chromosomal instability in amniocytes. Band 11q23, known to be involved in leukemogenesis, seems especially sensitive to genotoxic compounds contained in tobacco.


Infrared Reflection-Absorption Spectroscopy and STM Studies of Model Silica-Supported Copper Catalysts.
The structure of model silica-supported copper catalysts has been investigated with scanning tunneling microscopy (STM) and infrared reflection-absorption spectroscopy (IRAS). The IRAS studies of CO on the model silica-supported copper catalysts indicate that there are several types of copper clusters with surface structures similar to (111), (110), and other high-index planes of single-crystal copper. The STM studies show several types of copper clusters on silica and reveal images of metal clusters on an amorphous oxide support with atomic resolution.


An Immersed Boundary method with divergence-free velocity interpolation and force spreading.
The Immersed Boundary (IB) method is a mathematical framework for constructing robust numerical methods to study fluid-structure interaction in problems involving an elastic structure immersed in a viscous fluid. The IB formulation uses an Eulerian representation of the fluid and a Lagrangian representation of the structure. The Lagrangian and Eulerian frames are coupled by integral transforms with delta function kernels. The discretized IB equations use approximations to these transforms with regularized delta function kernels to interpolate the fluid velocity to the structure, and to spread structural forces to the fluid. It is well-known that the conventional IB method can suffer from poor volume conservation since the interpolated Lagrangian velocity field is not generally divergence-free, and so this can cause spurious volume changes. In practice, the lack of volume conservation is especially pronounced for cases where there are large pressure differences across thin structural boundaries. The aim of this paper is to greatly reduce the volume error of the IB method by introducing velocity-interpolation and force-spreading schemes with the properties that the interpolated velocity field in which the structure moves is at least C 1 and satisfies a continuous divergence-free condition, and that the force-spreading operator is the adjoint of the velocity-interpolation operator. We confirm through numerical experiments in two and three spatial dimensions that this new IB method is able to achieve substantial improvement in volume conservation compared to other existing IB methods, at the expense of a modest increase in the computational cost. Further, the new method provides smoother Lagrangian forces (tractions) than traditional IB methods. The method presented here is restricted to periodic computational domains. Its generalization to non-periodic domains is important future work.


Thromboembolic risk assessment and the efficacy of enoxaparin prophylaxis in excisional body contouring surgery.
There is a paucity of evidence within the plastic surgery literature concerning risk stratification and management of patients with respect to thromboembolic disease. A retrospective chart review was conducted to examine whether the Davison-Caprini risk-assessment model could stratify patients undergoing excisional body contouring surgery, allowing prophylaxis to be managed in an evidence-based manner. Three hundred sixty excisional body contouring patients at the University of Texas Southwestern Medical Center in Dallas, Texas, under the senior authors' (J.M.K. and R.J.R.) care were reviewed. Patients were stratified into groups according to the risk-assessment model and into groups based on procedure. Patient characteristics were investigated for their effects on thromboembolic risk. Complications of enoxaparin administration were analyzed. The data were analyzed using appropriate statistical procedures. The highest risk patients had a significantly increased rate of venous thromboembolism when compared with lower risk patients. Body mass index greater than 30 and hormone therapy use were associated with a significantly increased venous thromboembolism rate. Enoxaparin administration was associated with a statistically significant decrease in deep venous thrombosis in circumferential abdominoplasty patients. Enoxaparin administration was associated with higher bleeding rates. Low-molecular-weight heparin may affect the incidence of postoperative thrombotic complications in some surgical populations. In this study, patients who scored greater than four risk factors were at significant risk for venous thromboembolism. Enoxaparin significantly decreased deep venous thrombosis risk in patients undergoing circumferential abdominoplasty. This demonstrates the need for a multicenter, prospective, randomized study to examine various thromboembolic therapies and associated possible complications in these patients.


The safety and immunogenicity of Quadrivalent HPV (qHPV) vaccine in systemic lupus erythematosus.
This study evaluated the safety and immunogenicity of qHPV vaccine in SLE. Subjects: 34 women ages 19-50years (yrs.) with mild to moderate SLE & minimally active or inactive SLE received qHPV vaccine at the standard dosing schedule. active SLE disease (SELENA-SLEDAI>2), history of severe SLE disease, deep venous thrombosis, on >400mg/day of hydroxychloroquine, on >15mg/day of prednisone, or active infections. Patients were monitored for adverse events (AE), SLE flare, generation of thrombogenic antibodies and thrombosis. Antibody (Ab) levels to HPV 6, 11, 16 & 18 were measured by HPV competitive Luminex Immunoassay and Geometric Mean Titers (GMTs) were calculated for each HPV type. Seroconversion was assessed for those seronegative at baseline. The women in the study: African-American (79%), mean age=38.1years, mean age at diagnosis of SLE=28.6years, 35.3% had a history of smoking, 91% had 4 or more sexual partners, 50% had a history of sexually transmitted diseases, and 27.3% used condoms on a regular basis. Vaccine site reactions (VSRs) occurred in 62%, all mild. Ninety-seven percent experienced at least 1 non vaccine adverse event (nvAE) with a total of 493 nvAEs in 33 patients, of which 90% were mild and none were related to vaccine or SLE. There were 9 serious AEs, none were related to vaccine or SLE, all resolved. No patient experienced an SLE flare, thrombosis, or generation of thrombogenic antibodies. Seroconversion rate was 100% with mean GMTs comparable to Gardasil® package insert data. In this SLE vaccine study, qHPV vaccine was generally safe, well tolerated, and highly immunogenic. This clinical trial is registered on Clinical Trials.gov under number, NCT01741012 and was conducted under the FDA IND BB14113.


siRNA-chitosan complexes in poly(lactic-co-glycolic acid) nanoparticles for the silencing of aquaporin-1 in cancer cells.
A large number of studies document the strong expression of aquaporin-1 (AQP1) in tumor microvessels and correlate this aberrant expression with higher metastatic potential and aggressiveness of the malignancy. Although small animal experiments have shown that the modulation of AQP1 expression can halt angiogenesis and induce tumor regression, effective and safe strategies for the tissue specific inhibition of AQP1 are still missing. Here, small interference RNA-chitosan complexes encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are proposed for the intracellular delivery of siRNA molecules against AQP1. These NPs are coated with poly(vinyl alcohol) (PVA), to improve stability under physiological conditions, and demonstrate a diameter of 160 nm. The partial neutralization of the negatively charged siRNA molecules with the cationic chitosan enhances the loading by 5-fold, as compared to that of the free siRNA molecules, and allows one to modulate the release kinetics in the pH-dependent manner. At pH = 7.4, mimicking the conditions found in the systemic circulation, only the 40% of siRNA is released at 24 h post incubation; whereas at pH = 5.0, recreating the cell endosomal environment, all siRNA molecules are released in about 3 h. These NPs show no cytotoxicity on HeLa cells up to 72 h of incubation. In the same cells, transfected to overexpress AQP1, a silencing efficiency of 70% is achieved at 24 h post treatment with siRNA-loaded NPs. Confocal microscopy analysis of NP uptake demonstrates that siRNA molecules accumulate perinuclearly and in the nucleus. Given the stability, preferential release behavior, and well-known biocompatibility properties of PLGA nanostructures, these siRNA-loaded NPs hold potential for the efficient and safe in vivo silencing of AQPs via systemic administration.


Serum levels of fetal antigen 1 in extreme nutritional States.
Objective. Recent data suggest that fetal antigen (FA1) is linked to disorders of body weight. Thus, we measured FA1 serum levels in two extreme nutritional states of morbid obesity (MO) and anorexia nervosa (AN) and monitored its response to weight changes. Design. FA1 and insulin serum concentrations were assessed in a cross-sectional study design at defined time points after gastric restrictive surgery for 25 MO patients and 15 women with AN. Results. Absolute FA1 serum levels were within the assay normal range and were not different between the groups at baseline. However, the ratio of FA1/BMI was significantly higher in AN. FA1 was inversely correlated with BMI before and after weight change in AN, but not in MO patients. In addition, MO patients displayed a significant concomitant decrease of FA1 and insulin with the first 25% of EWL, while in AN patients a significant increase of FA1 was observed in association with weight gain. Conclusion. FA1 is a sensitive indicator of metabolic adaptation during weight change. While FA1 serum levels in humans generally do not correlate with BMI, our results suggest that changes in FA1 serum levels reflect changes in adipose tissue turnover.


The challenge of classifying poorly differentiated tumours in the lung.
The lung is a common site for primary carcinomas as well as a wide range of metastatic carcinomas and other rarer primary and secondary tumours that clinically and radiologically may mimic lung cancer. The World Health Organization classification of lung tumours is based on the morphological appearances in resected specimens. This provides a widely applicable system for classification, which, although complex, can be applied universally. The vast majority of patients with lung cancer, however, do not have their tumours resected, and the application of the same classification system to small biopsy specimens is problematic due in large part to sampling. Recognition of this has led to the widespread use of the term 'non-small cell carcinoma'. Future developments in our understanding of lung cancer and the development of novel targeted therapies may mean that in the future classification will become based more on the molecular features of tumours that predict response to therapies and prognosis rather than simple morphology. The predictive validity of such an approach using small biopsy or cytology specimens, however, still requires to be established. The problem of tumour heterogeneity, which is problematic for morphological classification, may also pose similar challenges for molecular approaches.


Admission selection criteria as predictors of outcomes in an undergraduate medical course: a prospective study.
In 1998, a new selection process which utilised an aptitude test and an interview in addition to previous academic achievement was introduced into an Australian undergraduate medical course. To test the outcomes of the selection criteria over an 11-year period. 1174 students who entered the course from secondary school and who enrolled in the MBBS from 1999 through 2009 were studied in relation to specific course outcomes. Regression analyses using entry scores, sex and age as independent variables were tested for their relative value in predicting subsequent academic performance in the 6-year course. The main outcome measures were assessed by weighted average mark for each academic year level; together with results in specific units, defined as either 'knowledge'-based or 'clinically' based. Previous academic performance and female sex were the major independent positive predictors of performance in the course. The interview score showed positive predictive power during the latter years of the course and in a range of 'clinically' based units. This relationship was mediated predominantly by the score for communication skills. Results support combining prior academic achievement with the assessment of communication skills in a structured interview as selection criteria into this undergraduate medical course.


Core molecule dependence of energy migration in phenylacetylene nanostar dendrimers: Ab initio molecular orbital-configuration interaction based quantum master equation study.
The core molecule dependence of energy (exciton) migration in phenylacetylene nanostar dendrimers is investigated using the ab initio molecular orbital (MO)-configuration interaction based quantum master equation approach. We examine three kinds of core molecular species, i.e., benzene, anthracene, and pentacene, with different highest occupied MO-lowest unoccupied MO (HOMO-LUMO) gaps, which lead to different orbital interactions between the dendron parts and the core molecule. The nanostars bearing anthracene and pentacene cores are characterized by multistep exciton states with spatially well-segmented distributions: The exciton distributions of high-lying exciton states are spatially localized well in the periphery region, whereas those of low-lying exciton states are done in the core region. On the other hand, for the nanostar bearing benzene core, which also has multistep exciton states, the spatial exciton distributions of low-lying exciton states are delocalized over the dendron and the core regions. It is found that the former nanostars exhibit nearly complete exciton migration from the periphery to the core molecule in contrast to the latter one, in which significant exciton distribution remains in the dendron parts attached to the core after the exciton relaxation, although all these dendrimers exhibit fast exciton relaxation from the initially populated states. It is predicted from the analysis based on the MO correlation diagrams and the relative relaxation factor that the complete exciton migration to the core occurs not only when the HOMO-LUMO gap of the core molecule is nearly equal to that of the dendron parts attached to the core (anthracene case) but also when fairly smaller than that (pentacene case), whereas the complete migration is not achieved when the HOMO-LUMO gap of the core is larger than that of the dendron parts (benzene case). These results suggest that the fast and complete exciton migration of real dendrimers could be realized by adjusting the HOMO-LUMO gap of the core molecule to be smaller than that of dendron parts, although there exist more complicated relaxation processes as compared to simple dendritic aggregate models studied so far.


Language proficiency and the enrollment of Medicaid-eligible children in publicly funded health insurance programs.
The purpose of the study was to examine the effect of language proficiency on enrollment in a state-sponsored child health insurance program. 1055 parents of Medicaid-eligible children, who were enrolled in a state-sponsored child health insurance program, were surveyed about how they learned about the state program, how they enrolled their children in the program, and perceived barriers to Medicaid enrollment. We performed weighted chi2 tests to identify statistically significant differences in outcomes based on language. We conducted multivariate analyses to evaluate the independent effect of language controlling for demographic characteristics. Almost a third of families did not speak English in the home. These families, referred to as limited English proficiency families, were significantly more likely than English-proficient families to learn of the program from medical providers, to receive assistance with enrollment, and to receive this assistance from staff at medical sites as compared to the toll-free telephone information line. They were also more likely to identify barriers to Medicaid enrollment related to "know-how"--that is, knowing about the Medicaid program, if their child was eligible, and how to enroll. Differences based on language proficiency persisted after controlling for marital status, family composition, place of residence, length of enrollment, and employment status for almost all study outcomes. This study demonstrates the significant impact of English language proficiency on enrollment of Medicaid-eligible children in publicly funded health insurance programs. Strong state-level leadership is needed to develop an approach to outreach and enrollment that specifically addresses the needs of those with less English proficiency.


Safety of screening with Human papillomavirus testing for cervical cancer at three-year intervals in a high-risk population: experience from the LAMS study.
To assess whether human papillomavirus (HPV) testing is a safe enough approach to warrant extension of the screening intervals of baseline Papanicolaou (Pap)-/HPV- women in low-income settings. Of the >1000 women prospectively followed up as part of the Latin American Screening (LAMS) Study in São Paulo, Campinas, Porto Alegre) and Buenos Aires, 470 women with both baseline cytology and Hybrid Capture 2 (HC2) results available were included in this analysis. These baseline Pap-negative and HC2- or HC2+ women were controlled at six-month intervals with colposcopy, HC2 and Pap to assess the cumulative risk of incident Pap smear abnormalities and their predictive factors. Of the 470 women, 324 (68.9%) were high-risk HPV (hrHPV) positive and 146 (31.1%) were negative. Having two or more lifetime sex partners (odds ratio [OR] = 2.63; 95% CI 1.70-3.51) and women using hormonal contraception (OR = 2.21; 95% CI 1.40-3.51) were at increased risk for baseline hrHPV infection. Baseline hrHPV+ women had a significantly increased risk of incident abnormal Pap smears during the follow-up. Survival curves deviate from each other starting at month 24 onwards, when hrHPV+ women start rapidly accumulating incident Pap smear abnormalities, including atypical squamous cells (ASC) or worse (log-rank; P < 0.001), low-grade squamous intraepithelial lesions (LSIL) or worse (P < 0.001) and high-grade squamous intraepithelial lesions (HSIL) (P = 0.03). Among the baseline hrHPV- women, the acquisition of incident hrHPV during the follow-up period significantly increased the risk of incident cytological abnormalities (hazard ratio = 3.5; 95% CI 1.1-11.7). These data implicate that HPV testing for hrHPV types might be a safe enough approach to warrant extension of the screening interval of hrHPV-/Pap-women even in low-resource settings. Although some women will inevitably contract hrHPV, the process to develop HSIL will be long enough to enable their detection at the next screening round (e.g. after three years).


Exercise-induced increase in serum creatine kinase is modified by subsequent bed rest.
This study was designed to find out if bed rest, which is known to markedly reduce peripheral lymph flow, immediately after strenuous exercise could affect the behaviour of creatine kinase activity (CK) in serum. Eleven endurance athletes performed an 18 km cross-country run, after which six of the subjects were placed in bed rest group (BR) for 23 hours, while a group of five control subjects maintained their normal habitual activity (C). After the bed rest all subjects performed a light jogging bout for 45 min. Seven hours after the exercise serum CK was increased threefold (p < 0.05) in both groups. During the next 16 hours serum CK increased further 30% in C (p < 0.05) but decreased (p < 0.05) in a similar magnitude in BR. Light jogging elicited a transient CK increase of 16% (p < 0.05) in C, but there was no change in BR. The fact that serum CK increased similarly in both groups during the first hours after the exercise shows that the transport of CK from muscles into circulation can be maintained for some hours despite absence of muscular activity. However, the later post-exercise serum CK response may be diminished by bed rest (effect of posture and/or lack of muscle function). The reduced response is also seen in the CK response to a repeated exercise. These observations suggest that a short-term physical inactivity (bed rest) may reduce both the lymphatic transport of CK and the release of enzyme from muscle fibres.


Population biology of Ostertagia ostertagi and anthelmintic strategies against ostertagiasis in calves.
Five chemoprophylactic or chemotherapeutic strategies against bovine ostertagiasis are compared using a mathematical model of the population biology of Ostertagia ostertagi. The model offers a means of screening novel strategies prior to their further investigation in the field. Under conditions of climate and management typical of many regions in Northern temperate Europe, the model indicates that all of the tested prophylactic strategies will result in a profound reduction in the intensity of infection in grazing beef calves when compared with an untreated control group or the simple therapeutic protocol. Not all of those strategies which caused diminution in the scale of the midsummer rise in pasture larval contamination resulted in progressively less contaminated pastures in subsequent years. Moreover, the reproductive potential of the parasite is so great that the principal advantage of the 'pasture cleaning' effect that is the consequence of some protocols is not that the pasture may eventually be used to graze untreated calves but that the treated animals are subjected to a progressively smaller parasitic challenge with the concomitant pay-off in production gains.


A Systematic Review of Global Health Assessment for Education in Healthcare Professions.
Emphasis on global health education is growing, with schools/colleges developing relevant courses, areas of concentration, and other didactic content. Organizations such as the Consortium of Universities for Global Health (CUGH) provide guidance for competencies in global health, but evaluation strategies are lacking. Accordingly, the purpose of this study was to identify methods and tools utilized to assess knowledge, skills, and attitudes in global health courses for health science students. A systematic review was conducted according to the PRISMA guidelines. The initial search was conducted using controlled vocabularies to screen PubMed, EMBASE, Global Health using Ovid, CINAHL, and ERIC from January 1997 to March 2020. Included articles detailed students in health professions, described a didactic educational intervention related to global health, and described assessment strategies and results. A total of 12,113 titles/abstracts were identified. Based on the study inclusion criteria, 545 full texts were reviewed, and 79 full-text articles were selected for qualitative synthesis. Findings of the research revealed that cultural competence (70.9%) was evaluated most often, followed by health disparities (26.6%) and global health itself (12.7%). Most articles used quantitative assessment methods (86.1%), with surveys being the predominant method. A total of 91.1% of studies assessed perceptions, attitudes, and beliefs, while fewer evaluated knowledge (43.0%) and skills (19.0%). The most common validated tool employed was the Inventory for Assessing the Process of Cultural Competence (IAPCC). Based of the results of this study, the majority of the assessment tools utilized for global health education focused on cultural competence. One of the important findings of this research is the lack of validated instruments to assess students' skills in health disparities and global health. Given the recent global pandemic, these skills are essential for educating health care professionals to enhance global health.


Development of Fe3O4 core-TiO2 shell nanocomposites and nanoconjugates as a foundation for neuroblastoma radiosensitization.
Neuroblastoma is the most common extracranial solid malignancy in childhood which, despite the current progress in radiotherapy and chemotherapy protocols, still has a high mortality rate in high risk tumors. Nanomedicine offers exciting and unexploited opportunities to overcome the shortcomings of conventional medicine. The photocatalytic properties of Fe3O4 core-TiO2 shell nanocomposites and their potential for cell specific targeting suggest that nanoconstructs produced using Fe3O4 core-TiO2 shell nanocomposites could be used to enhance radiation effects in neuroblastoma. In this study, we evaluated bare, metaiodobenzylguanidine (MIBG) and 3,4-Dihydroxyphenylacetic acid (DOPAC) coated Fe3O4@TiO2 as potential radiosensitizers for neuroblastoma in vitro. The uptake of bare and MIBG coated nanocomposites modestly sensitized neuroblastoma cells to ionizing radiation. Conversely, cells exposed to DOPAC coated nanocomposites exhibited a five-fold enhanced sensitivity to radiation, increased numbers of radiation induced DNA double-strand breaks, and apoptotic cell death. The addition of a peptide mimic of the epidermal growth factor (EGF) to nanoconjugates coated with MIBG altered their intracellular distribution. Cryo X-ray fluorescence microscopy tomography of frozen hydrated cells treated with these nanoconjugates revealed cytoplasmic as well as nuclear distribution of the nanoconstructs. The intracellular distribution pattern of different nanoconjugates used in this study was different for different nanoconjugate surface molecules. Cells exposed to DOPAC covered nanoconjugates showed the smallest nanoconjugate uptake, with the most prominent pattern of large intracellular aggregates. Interestingly, cells treated with this nanoconjugate also showed the most pronounced radiosensitization effect in combination with the external beam x-ray irradiation. Further studies are necessary to evaluate mechanistic basis for this increased radiosensitization effect. Preliminary studies with the nanoparticles carrying an EGF mimicking peptide showed that this approach to targeting could perhaps be combined with a different approach to radiosensitization - use of nanoconjugates in combination with the radioactive iodine. Much additional work will be necessary in order to evaluate possible benefits of targeted nanoconjugates carrying radionuclides. The online version contains supplementary material available at 10.1186/s12645-021-00081-z.


Epileptic synapsin triple knockout mice exhibit progressive long-term aberrant plasticity in the entorhinal cortex.
Studying epileptogenesis in a genetic model can facilitate the identification of factors that promote the conversion of a normal brain into one chronically prone to seizures. Synapsin triple-knockout (TKO) mice exhibit adult-onset epilepsy, thus allowing the characterization of events as preceding or following seizure onset. Although it has been proposed that a congenital reduction in inhibitory transmission is the underlying cause for epilepsy in these mice, young TKO mice are asymptomatic. We report that the genetic lesion exerts long-term progressive effects that extend well into adulthood. Although inhibitory transmission is initially reduced, it is subsequently strengthened relative to its magnitude in control mice, so that the excitation to inhibition balance in adult TKOs is inverted in favor of inhibition. In parallel, we observed long-term alterations in synaptic depression kinetics of excitatory transmission and in the extent of tonic inhibition, illustrating adaptations in synaptic properties. Moreover, age-dependent acceleration of the action potential did not occur in TKO cortical pyramidal neurons, suggesting wide-ranging secondary changes in brain excitability. In conclusion, although congenital impairments in inhibitory transmission may initiate epileptogenesis in the synapsin TKO mice, we suggest that secondary adaptations are crucial for the establishment of this epileptic network.


Segregation distortion: Utilizing simulated genotyping data to evaluate statistical methods.
Segregation distortion is the phenomenon in which genotypes deviate from expected Mendelian ratios in the progeny of a cross between two varieties or species. There is not currently a widely used consensus for the appropriate statistical test, or more specifically the multiple testing correction procedure, used to detect segregation distortion for high-density single-nucleotide polymorphism (SNP) data. Here we examine the efficacy of various multiple testing procedures, including chi-square test with no correction for multiple testing, false-discovery rate correction and Bonferroni correction using an in-silico simulation of a biparental mapping population. We find that the false discovery rate correction best approximates the traditional p-value threshold of 0.05 for high-density marker data. We also utilize this simulation to test the effect of segregation distortion on the genetic mapping process, specifically on the formation of linkage groups during marker clustering. Only extreme segregation distortion was found to effect genetic mapping. In addition, we utilize replicate empirical mapping populations of wheat varieties Avalon and Cadenza to assess how often segregation distortion conforms to the same pattern between closely related wheat varieties.


Hyperspectral sensing of disease stress in the Caribbean reef-building coral, Orbicella faveolata - perspectives for the field of coral disease monitoring.
The effectiveness of management plans developed for responding to coral disease outbreaks is limited due to the lack of rapid methods of disease diagnosis. In order to fulfill current management guidelines for responding to coral disease outbreaks, alternative methods that significantly reduce response time must be developed. Hyperspectral sensing has been used by various groups to characterize the spectral signatures unique to asymptomatic and bleached corals. The 2010 combined bleaching and Caribbean yellow band disease outbreak in Puerto Rico provided a unique opportunity to investigate the spectral signatures associated with bleached and Caribbean yellow band-diseased colonies of Orbicella faveolata for the first time. Using derivative and cluster analyses of hyperspectral reflectance data, the present study demonstrates the proof of concept that spectral signatures can be used to differentiate between coral disease states. This method enhanced predominant visual methods of diagnosis by distinguishing between different asymptomatic conditions that are identical in field observations and photographic records. The ability to identify disease-affected tissue before lesions become visible could greatly reduce response times to coral disease outbreaks in monitoring efforts. Finally, spectral signatures associated with the poorly understood Caribbean yellow band disease are presented to guide future research on the role of pigments in the etiology.


Reduction of current density at disk electrode periphery by shaping current pulse edges.
Previous studies reveal that the primary distribution of the current density is sharply enhanced at the edge of a disk electrode submerged into a semi-infinite space of conductive solution. The current enhancement will cause the double layer capacitance at the periphery of the electrode to be charged much faster compared to the center, and can also lead to severe corrosion at the edge. While several studies focused on the geometric design of the electrode to reduce this enhancement, we explore the feasibility of achieving similar effect by shaping the edges of the current input. The simulation uses finite element analysis software to solve the system of partial differential equations and results show that the edge enhancement could be greatly reduced without significantly changing the input efficacy of current and/or charge.


Mitochondrial phylogeography of the Woodmouse (Apodemus sylvaticus) in the Western Palearctic region.
We sequenced 965 base pairs of the mitochondrial DNA cytochrome b from 102 woodmice (Apodemus sylvaticus) collected from 40 European localities. The aims of the study were to answer the following questions. (i) Did the Mediterranean peninsulas play a role as refuge for woodmice? (ii) Is genetic variability of A. sylvaticus higher in the Mediterranean region compared with northern Europe? (iii) Are the patterns of the postglacial colonization of Europe by woodmice similar to those presently recognized for other European species? The results provide a clear picture of the impact of the Quaternary glaciations on the genetic and geographical structure of the woodmouse. Our analyses indicate a higher genetic variability of woodmice in the Mediterranean peninsulas compared to northern Europe, suggesting a role of the former as refuge regions for this small mammal. An original pattern of postglacial colonization is proposed where the Iberian and southern France refuge populations colonized almost all European regions. The Sicilian population appears to be very differentiated and highly variable. This emphasizes the importance of this island as a 'hot spot' for the intraspecific genetic diversity of the woodmouse. Finally, woodmice in North Africa originated from southwestern Europe, most probably as a result of a recent anthropogenic introduction.


Preoperative work-up and criteria.
No matter what the underlying podiatric problem, if surgical correction is considered, a good preoperative work-up is essential. This article deals with the preoperative work-up and criteria for a variety of ambulatory surgical procedures.


Periodontal regeneration with a combination of enamel matrix proteins and autogenous bone grafting.
Attempts to stimulate periodontal regeneration in the past have focused on either filling the defect with some type of material or providing a space for host cells to repopulate the site and elicit new tissue. In some cases, these approaches have been combined with the assumption that the filler material will help maintain the space necessary for the host cells to invade the area. Growth stimulating substances such as growth factors and other proteins have also been used to encourage periodontal tissue regeneration and histological evaluation supports the use of these substances. Thus, the role for and the necessity of a certain amount of space maintenance for periodontal regeneration is not exactly understood. In addition, it is not known if there is some critical size required for space maintenance or for exactly how long the space must be maintained in order for the host cells to stimulate new cementum, periodontal ligament, and bone. The goal of this study was to evaluate periodontal regeneration in intrabony defects of various sizes treated with a combination of enamel matrix proteins and autogenous bone graft. Periodontal defects ranging in size from 1 to 6 mm were randomized and created bilaterally beside three teeth in the mandibles of baboons. Plaque was allowed to accumulate around wire ligatures placed into the defects. After 2 months, the wire ligatures were removed, the teeth and roots scaled and root planed, and a notch was placed with a chisel at the base of the defect. On one side of the mandible, neutral ethylene diamine tetracetic acid and enamel matrix derivative (EMD) were first used to treat the defect. Autogenous bone taken from the same surgical site was treated with enamel matrix derivative in a dampen dish and then added to the EMD-treated defects. The other side of the mandible served as control with neutral ethylene diamine tetracetic acid and scaling and root planing. Flaps were sutured and the animals were allowed to heal without oral hygiene procedures. After 5 months, the animals were sacrificed and the teeth were processed for histological evaluation. The results revealed new cementum, periodontal ligament with Sharpey's fibers, and new bone tissue similar to native periodontal tissues. Remnants of the autogenous bone chips were still present at this 5-month post-healing period. Thus periodontal regeneration occurred in all sizes of the periodontal defects. In general, EMD plus autogenous graft treatment resulted in greater tissue formation than controls. In fact, in many cases, very dramatic tissue formation occurred far coronal to the base of the defects in the EMD plus autogenous graft-treated lesions. In addition, horizontal bone fill occurred in the defects and was prominent in the 4 or 6 mm wide lesions. When evaluating the combined 1 and 2 mm defects, the height of new cementum with EMD plus graft was 3.88 mm versus 2.03 mm in the controls, a statistically significant (P < 0.005) difference. In the wider (4 and 6 mm) lesions, this difference was not significant and was much less between treated and control lesions with 2.78 and 2.57 mm of new cementum respectively. In the case of new bone height, in the smaller lesions EMD plus graft resulted in 4.00 mm new bone versus 2.22 mm in the controls, again a statistically significant (P < 0.005) difference. In the larger lesions, EMD plus autogenous bone graft had 3.24 mm new bone height compared to 2.71 mm in the controls, a difference that was not statistically significant. Additionally, in the smaller lesions, new cementum width at the level of the notch was twice as great (statistically significant, P < 0.015) in the EMD plus graft sites compared to control. The width of the periodontal ligament at the coronal aspect of the new bone tissue was similar in the smaller lesions between treated and control sites. The results from the wider defects must be interpreted cautiously as the interproximal bone heights were remodeled adjacent to the wider defects and likely limited the potential for regeneration. The combination of enamel matrix derivative plus autogenous bone graft stimulated statistically significant periodontal regeneration in the more narrow 1 and 2 mm lesions. No statistically significant difference was observed in the wider 4 and 6 mm lesions. In many cases, dramatic amounts of new cementum, Sharpey's fibers, periodontal ligament, and bone tissue were formed far above the notch placed at the base of the contaminated defects. This was especially significant considering the width of some of the defects and the fact that no oral hygiene was performed over the 5-month healing period. This periodontal regeneration occurred in the absence of exogenous growth factors or barrier membranes. In summary, the combination of enamel matrix derivative and autogenous bone represents a therapeutic combination that can be highly effective in stimulating significant amounts of periodontal regeneration.


Skin color, sex, and educational attainment in the post-civil rights era.
We assess the relationship between skin color and educational attainment for native-born non-Hispanic Black and White men and women, using data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study. CARDIA is a medical cohort study with twenty years of social background data and a continuous measure of skin color, recorded as the percent of light reflected off skin. For Black men and women, we find a one-standard-deviation increase in skin lightness to be associated with a quarter-year increase in educational attainment. For White women, we find an association approximately equal in magnitude to that found for Black respondents, and the pattern of significance across educational transitions suggests that skin color for White women is not simply a proxy for family background. For White men, any relationship between skin color and attainment is not robust and, analyses suggest, might primarily reflect differences in family background. Findings suggest that discrimination on the basis of skin color may be less specific to race than previously thought.