Analysis of land cover/use changes using Landsat 5 TM data and indices.
Urban expansion and unprecedented rural to urban transition, along with a huge population growth, are major driving forces altering land cover/use in metropolitan areas. Many of the land cover classes such as farmlands, wetlands, forests, and bare soils have been transformed during the past years into human settlements. Identification of the city growth trends and the impact of it on the vegetation cover of an area is essential for a better understanding of the sustainability of urban development processes, both planned and unplanned. Analyzing the causes and consequences of land use dynamics helps local government, urban planners, and managers for the betterment of future plans and minimizing the negative effects.This study determined temporal changes in vegetation cover and built-up area in Istanbul (Turkey) using the normalized difference vegetation index (NDVI), soil-adjusted vegetation index (SAVI), and built-up area index (BUAI). The temporal data were based on Landsat 5 Thematic Mapper (TM) images acquired in June of 1984, 2002, 2007, 2009, and 2011. The NDVI was applied to all the Landsat images, and the resulting NDVI images were overlaid to generate an NDVI layer stack image. The same procedure was repeated using the SAVI and BUAI images. The layer stack images revealed those areas that had changed in terms of the different indices over the years. To determine temporal change trends, the values of 150 randomly selected control points were extracted from the same locations in the NDVI, SAVI, and BUAI layer stack images. The results obtained from these control points showed that vegetation cover decreased considerably because of a remarkable increase in the built-up area.


Evaluation of delayed appearance of acetazolamide effect in patients with chronic cerebrovascular ischemic disease: feasibility and usefulness of SPECT method using triple injection of ECD.
The purpose of this study was to verify the feasibility and usefulness of a new SPECT method, called triple injection of (99m)Tc-ethylcysteinate dimer (TIE), in evaluation of the delayed or poor appearance of acetazolamide (ACZ) effects in patients with chronic cerebral ischemic disease. Three equal-volume splits of (99m)Tc-ethylcysteinate dimer were intravenously administered, and 1,000 mg ACZ were used as a vasodilator. A middle cerebral artery territory in the lateral ventricle was used as a region of interest. The data at rest and at 7.5 and 20 min after ACZ challenge (ACZ 7.5 and ACZ 20, respectively) were obtained by dynamic SPECT, and a time response curve to ACZ was obtained through the relative ratio of regional counts to the data at rest, not through regional cerebral blood flow. Nine cases of complete occlusion of the internal carotid artery (IC) and 6 cases of severe IC stenosis were analyzed. In 12 healthy volunteers (24 cerebral hemispheres) using a placebo (negative control), the values at rest and at rest 7.5 and rest 20 (corresponding to ACZ 7.5 and ACZ 20, respectively) were 100%, 100.4% +/- 2.8%, and 99.6% +/- 3.6%, respectively, indicating the accuracy of the TIE method. In a positive control using 24 normal cerebral hemispheres, prompt maximal vasoreactivity at ACZ 7.5 (124.5% +/- 8.0%) was confirmed, as was continuous vasoreactivity until ACZ 20 (130.1% +/- 12.8%). The values between ACZ 7.5 and ACZ 20 were not statistically different. Patients with complete IC occlusion exhibited a poor response at ACZ 7.5 despite a normal response at ACZ 20 (delayed response). Furthermore, in patients with severe IC stenosis, restoration of cerebrovascular reactivity after carotid endarterectomy was confirmed not only at ACZ 20 but also at ACZ 7.5. The TIE method using SPECT may be a potentially useful and sensitive strategy in clinical evaluation of the delayed or poor appearance of ACZ effects in patients with chronic cerebrovascular ischemic disease.


Kinetics of humoral immune response and severity of infection after three doses of SARS-CoV-2 mRNA vaccine in a large cohort of kidney transplant recipients.
COVID-19 in kidney transplant recipients is associated with high morbidity and mortality. In this study we aimed to evaluate: (i) the seroconversion rate after BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 vaccine, (ii) factors associated with humoral response, (iii) clinical outcome of COVID-19 in kidney transplanted patients. We enrolled a cohort of 743 kidney transplant recipients followed up from March 2020 until April 2022. A subset of 336 patients, who received three-doses of SARS-CoV-2 vaccine, was analyzed in terms of kinetics of humoral immune response and compared to a control group of 94 healthcare workers. Antibody response was tested before vaccination (T0), 15 and 90 days after the second dose (T1 and T2), on the day of the third dose (T3) and one month after the third dose (T4). We observed that 66 out of 743 subjects had COVID-19 infection pre-vaccination: 65.2% had severe symptoms, 27.3% were hospitalized (9 deaths), none were asymptomatic. After three doses, 51 patients had COVID-19 infection, 60.8% were asymptomatic, 27.5% reported mild symptoms, 3.9% showed severe symptoms, 7.8% were hospitalized (2 deaths). In the subset of 336 vaccinated patients, an antibody level > 0.8 U/ml was detected at T1, that increased at T2 and T3, peaking at T4. Independent factors associated with a negative antibody titer at T4 were decreasing estimated glomerular filtration rate, time from transplantation, and antimetabolites (all p < 0.001) and age (p = 0.007). The kinetics of humoral response after three doses of vaccine in kidney transplant patients is characterized by a late but effective immune response against SARS-CoV-2, reducing morbidity and mortality.


Resonance raman characterization of reaction centers with an Asp residue near the photoactive bacteriopheophytin.
Qy-excitation resonance Raman (RR) studies are reported for a series of Rhodobacter capsulatus reaction centers (RCs) containing mutations at L-polypeptide residue 121 near the photoactive bacteriopheophytin (BPhL). The studies focus on the electronic/structural perturbations of BPhL induced by replacing the native Phe with an Asp residue. Earlier work has shown that the electron-transfer properties of F(L121)D RCs are closely related to those of RCs in which BPhL is replaced by bacteriochlorophyll (BChl) (beta-type RCs) or by pheophytin. In addition to the F(L121)D single mutant, RR studies were performed on the F(L121)D/E(L104)L double mutant, which additionally removes the hydrogen bond between BPhL and the native Glu L104 residue. The vibrational signatures of BPhL in the single and double mutants containing Asp L121 are compared with one another and with those of BPhL in both wild-type and F(L121)L RCs. The replacement of the aromatic Phe residue with Leu has no discernible effect on the vibrational properties of BPhL, a finding in concert with the previously reported absence of an effect of the mutation on the electron-transfer characteristics of the RC. In contrast, replacement of Phe with Asp significantly perturbs the vibrational characteristics of BPhL, and in a manner most consistent with Asp L121 being deprotonated and negatively charged. The negative charge of the carboxyl group of Asp L121 interacts with the pi-electron system of BPhL in a relatively nonspecific fashion, diminishing the contribution of charge-separated resonance forms of the C9-keto group to the electronic structure of the cofactor. The presence of a negative charge near BPhL is consistent with the known photochemistry of F(L121)D RCs, which indicates that the free energy of P+BPhL- is substantially higher than in wild-type RCs.


Effect of 7-nitroindazole alone and in combination with phenobarbitone and diazepam on picrotoxin-induced convulsions in rats.
There are no reports on the effect of 7-nitroindazole (7-NI) on chemically-induced convulsions. Hence, in the present study, its (100 and 200 mg/kg) action was tested alone and in combination with phenobarbitone (20 mg/kg) and diazepam (0.25 mg/kg) on picrotoxin (PCT)-induced convulsions in rats. The changes produced by 7-NI on nitric oxide synthase (NOS) activity and nitric oxide (NO) concentration were determined in the brain. The effect of 7-NI was tested in L-arginine (1000 mg/kg) pretreated (30 min) animals. The smaller dose (100 mg/kg) of 7-NI did not alter NOS activity and NO concentration, but inhibited PCT-induced convulsions indicating that its anticonvulsant action was devoid of an involvement of NO. But, an inhibition of NOS activity, by a larger (200 mg/kg) dose of it, resulted in a promotion of the convulsant action of PCT and in an impairment of the anticonvulsant effect of both phenobarbitone and diazepam. The proconvulsant action of 7-NI was reverted by L-arginine. These results suggest that 100 and 200 mg/kg of 7-NI produce distinguishable action on PCT-induced convulsions because NOS activity is inhibited by 200 mg/kg and not by 100 mg/kg of it. The results further suggest that NO acts as anticonvulsant and that the NOS inhibitors, like 7-NI, cannot be used as an anticonvulsant either alone or in combination with other anticonvulsants.


Adiponectin concentration in mid-trimester amniotic fluid varies with the α-amylase level and maternal and neonatal outcomes.
Factors influencing intraamniotic adiponectin levels and their functional significance remain incompletely elucidated. We prospectively measured adiponectin in amniotic fluid and identified its associations with maternal parameters, mediators in amniotic fluid and pregnancy outcomes. Mid-trimester amniotic fluid from 571 women was tested for adiponectin, interleukin (IL)-6, IL-8 and α-amylase by enzyme-linked immunosorbant assay (ELISA), after which clinical data were obtained. Correlations between adiponectin and clinical or laboratory variables were analyzed by the Kruskal-Wallis, Mann-Whitney and Spearman rank correlation tests. As compared to median levels in 462 women with a term delivery (7.8 ng/mL), adiponectin was elevated in 14 women who subsequently developed preterm premature rupture of membranes (pPROM) (17.3 ng/mL) and 24 women with an iatrogenic preterm birth (IPTB) (13.9 ng/mL) (P=0.0003), but not in 30 women who subsequently had a spontaneous preterm birth with intact membranes (8.1 ng/mL) (P>0.05). Median adiponectin was also elevated in 13 women whose babies developed fetal growth restriction (FGR) (20.6 ng/mL) (P=0.0055) and in 22 women whose babies had respiratory distress syndrome (RDS) (23.0 ng/mL) (P<0.0001). The adiponectin concentration was positively correlated with amylase (P=0.0089) and inversely correlated with maternal body mass index (P=0.0045). Adiponectin is a component of mid-trimester amniotic fluid and its concentration varies with maternal body mass index and subsequent development of pPROM, IPTB, FGR and RDS.


Dysfunction of dopamine homeostasis: clues in the hunt for novel Parkinson's disease therapies.
Parkinson's disease is the second most common neurodegenerative disorder and, at present, has no cure. Both environmental and genetic factors have been implicated in the etiology of the disease; however, the pathogenic pathways leading to neuronal degeneration are still unclear. Parkinson's disease is characterized by the preferential death of a subset of neurons in the mesencephalon that use dopamine as neurotransmitter for synaptic communication. Dopamine is a highly reactive molecule that can lead to cytotoxicity if not properly stored and metabolized. Targeting any of the pathways that tightly control this neurotransmitter holds great therapeutic expectations. In this article we present a comprehensive overview of the cellular pathways that control dopamine fate and discuss potential therapeutic approaches to counteract or slow Parkinson's disease onset and progression.


The process followed in the development of the paediatric food-based dietary guidelines for South Africa.
In 1996, a Food and Agricultural Organization/World Health Organization expert panel proposed the development of food-based dietary guidelines (FBDGs) that would be unique and specific to the needs of the populations of different countries. In 1997, a South African FBDG Working Group was initiated to develop a single set of FBDGs aimed at optimal nutrition for all South Africans older than 5 years. Thereafter, additional working groups investigated the development of FBDGs for specific priority groups including HIV/AIDS sufferers, the elderly, pregnant and lactating women and children under 5 years. This resulted in the formation of an expert paediatric FBDG Working Group in 2000, in Cape Town with the task to develop paediatric FBDGs (PFBDGs) for children younger than 5 years. However, it was decided to raise the 5-year-age limit to 7 years, which corresponds to one of the recommended dietary allowance (RDA) cut-offs for both genders and that would cover most pre-schoolers. Ultimately, three age subcategories were identified for developing specific PFBDGs, i.e. 0-6 months, 6-12 months and 12-84 months. In May 2003, after thorough review of the relevant literature, discussions with various stakeholders and pre-testing for comprehensibility, a set of preliminary PFBDGs for each of the subcategories was approved by the Working Group to be subjected to consumer testing. The proposed guidelines were considered to be the most appropriate ones for each age group, based on scientific and local evidence, and were evaluated utilizing qualitative methodologies. The results of these data are presented and discussed below. However, further testing is required for the diverse groups in the country.


Prediction of Alzheimer's Disease-Associated Genes by Integration of GWAS Summary Data and Expression Data.
Alzheimer's disease (AD) is the most common cause of dementia. It is the fifth leading cause of death among elderly people. With high genetic heritability (79%), finding the disease's causal genes is a crucial step in finding a treatment for AD. Following the International Genomics of Alzheimer's Project (IGAP), many disease-associated genes have been identified; however, we do not have enough knowledge about how those disease-associated genes affect gene expression and disease-related pathways. We integrated GWAS summary data from IGAP and five different expression-level data by using the transcriptome-wide association study method and identified 15 disease-causal genes under strict multiple testing (α < 0.05), and four genes are newly identified. We identified an additional 29 potential disease-causal genes under a false discovery rate (α < 0.05), and 21 of them are newly identified. Many genes we identified are also associated with an autoimmune disorder.


Antioxidant Potential in Different Parts and Callus of Gynura procumbens and Different Parts of Gynura bicolor.
Plants from Gynura family was used in this study, namely, Gynura procumbens and Gynura bicolor. Gynura procumbens is well known for its various medicinal properties such as antihyperglycaemic, antihyperlipidaemic, and antiulcerogenic; meanwhile, G. bicolor remains unexploited. Several nonenzymatic antioxidants methods were utilized to study the antioxidant capacity, which include ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, total flavonoid content, total phenolic content, and ascorbic acid content determination. DPPH assay reveals G. procumbens shoot as the lowest (66.885%) and G. procumbens root as the highest (93.499%) DPPH radical inhibitor. In FRAP assay, reducing power was not detected in G. procumbens leaf callus (0.000 TEAC mg/g FW) whereby G. procumbens root exhibits the highest (1.103 TEAC mg/g FW) ferric reducing power. Total phenolic content and total flavonoid content exhibited similar trend for both the intact plants analysed. In all antioxidant assays, G. procumbens callus culture exhibits very low antioxidant activity. However, G. procumbens root exhibited highest phenolic content, flavonoid content, and ascorbic acid content with 4.957 TEAC mg/g FW, 543.529 QE µg/g FW, and 54.723 µg/g FW, respectively. This study reveals that G. procumbens root extract is a good source of natural antioxidant.


Case management guideline: Alzheimer disease and other dementias.
Case management guidelines are an integration of information obtained from research, observations, clinical experience, and judgments of expert clinicians, scientists, and clients. This guideline integrates information from multiple practice guidelines in order to guide the case manager in managing clients with Alzheimer disease and other dementias. The guideline provides direction in recognition of symptoms or triggers, risk factors, possible complications, case management outcomes, barriers to effective outcomes, goals, providers/practitioners, treatment options, location of treatment, estimated cost of treatment, psychosocial issues, life planning and long-term planning, vocational issues and teaching protocols. In addition, resource contacts and sources for major instruments used in measuring Alzheimer disease and dementia are presented.


Occurrence and neuroendocrine role of D-aspartic acid and N-methyl-D-aspartic acid in Ciona intestinalis.
Probes for the occurrence of endogenous D-aspartic acid (D-Asp) and N-methyl-D-aspartic acid (NMDA) in the neural complex and gonads of a protochordate, the ascidian Ciona intestinalis, have confirmed the presence of these two excitatory amino acids and their involvement in hormonal activity. A hormonal pathway similar to that which occurs in vertebrates has been discovered. In the cerebral ganglion D-Asp is synthesized from L-Asp by an aspartate racemase. Then, D-Asp is transferred through the blood stream into the neural gland where it gives rise to NMDA by means of an NMDA synthase. NMDA, in turn, passes from the neuronal gland into the gonads where it induces the synthesis and release of a gonadotropin-releasing hormone (GnRH). The GnRH in turn modulates the release and synthesis of testosterone and progesterone in the gonads, which are implicated in reproduction.


Impacts of K-12 school reopening on the COVID-19 epidemic in Indiana, USA.
In the United States, schools closed in March 2020 due to COVID-19 and began reopening in August 2020, despite continuing transmission of SARS-CoV-2. In states where in-person instruction resumed at that time, two major unknowns were the capacity at which schools would operate, which depended on the proportion of families opting for remote instruction, and adherence to face-mask requirements in schools, which depended on cooperation from students and enforcement by schools. To determine the impact of these conditions on the statewide burden of COVID-19 in Indiana, we used an agent-based model calibrated to and validated against multiple data types. Using this model, we quantified the burden of COVID-19 on K-12 students, teachers, their families, and the general population under alternative scenarios spanning three levels of school operating capacity (50 %, 75 %, and 100 %) and three levels of face-mask adherence in schools (50 %, 75 %, and 100 %). Under a scenario in which schools operated remotely, we projected 45,579 (95 % CrI: 14,109-132,546) infections and 790 (95 % CrI: 176-1680) deaths statewide between August 24 and December 31. Reopening at 100 % capacity with 50 % face-mask adherence in schools resulted in a proportional increase of 42.9 (95 % CrI: 41.3-44.3) and 9.2 (95 % CrI: 8.9-9.5) times that number of infections and deaths, respectively. In contrast, our results showed that at 50 % capacity with 100 % face-mask adherence, the number of infections and deaths were 22 % (95 % CrI: 16 %-28 %) and 11 % (95 % CrI: 5 %-18 %) higher than the scenario in which schools operated remotely. Within this range of possibilities, we found that high levels of school operating capacity (80-95 %) and intermediate levels of face-mask adherence (40-70 %) resulted in model behavior most consistent with observed data. Together, these results underscore the importance of precautions taken in schools for the benefit of their communities.


Clastogenic effects of the dithiocarbamate fungicides thiram and ziram in Chinese hamster cell lines cultured in vitro.
We report here the results obtained using the dithiocarbamate fungicides thiram and ziram to investigate the induction of chromosomal aberrations (CAs) in Chinese hamster ovary (CHO) cells both in the absence and presence of S9 metabolism, and in a Chinese hamster epithelial liver (CHEL) cells which retain metabolic competence to activate different classes of promutagens/procarcinogens. Both thiram and ziram proved to be strong chromosome breaking agents in the CHEL cells and CHO cells in the presence of S9 metabolism. These findings suggest that thiram and ziram require metabolic conversion to become genetically active, and corroborate the evidence that CHEL cells are suitable to activate and detect a broad spectrum of chemical procarcinogens including these two pesticides.


Model study on the effect of 15 phenolic olive mill wastewater constituents on seed germination and Vibrio fischeri metabolism.
Olive mill wastewaters (OMW) can be a severe problem when disposed of as untreated because of their high organic load, elevated concentration of polyphenols, and moderately low biodegradability. In the present study, the acute toxicity of 15 compounds with low molecular weight (<350 Da), catechol, four benzoic acids, three phenylacetic acids, three phenylethanols, and four cinnamic acids, already isolated from the reverse osmosis in the fractionation of OMW, was assessed on the marine bacterium Vibrio fischeri and on the seeds of two dicotyledonous species Cucumis sativus and Lepidium sativum, and on one monocotyledon Sorghum bicolor. Results of phytotoxicity showed that the most toxic compounds were catechol (EC50s ranging from 0.40 mmol/L for S. bicolor to 1.09 for C. sativus) and hydroxytyrosol, (EC50s ranging from 0.47 mmol/L for S. bicolor to 1.55 for C. sativus) while the toxic potential on bacteria was particularly elevated with EC50 values 1 or 2 orders less than phytotoxicity. These results suggested that the risk of OMW disposal may be more elevated for the water compartment than for the soil.


Social determinants of dietary habits in Denmark.
To investigate whether there is an association between socioeconomic status and a healthy diet, taking the possible influence of other social variables such as age, gender, income and household composition into consideration. Cross-sectional study. Nationwide study in Denmark, 1995. Random sample from the civil registration system. A total of 852 men and 870 women aged 18-80 y participated, a response rate of 58%. A 7 day estimated dietary record was used to obtain information about the diet. Information about social background was gained through face-to-face interview. The intake of fruit and vegetables and the percentage energy (E%) from fat in the diet were significantly associated with the educational level of both men and women. For men with only basic schooling, the mean intake of vegetables and fat was 84 g/10 MJ and 41 E% respectively. Men with long higher education had a mean intake of 119 g/10 MJ of vegetables and 37 E% of fat. For women, the corresponding figures for the intake of vegetables and fat were 131 g/10 MJ and 38 E% and 175 g/10 MJ and 37 E%, respectively. For women, age, income and household composition were also significantly associated with the intake of fruit and vegetables. Education seems to be the most important social variable to explain social differences in dietary habits. Additional variables are needed to explain dietary habits of women. Differences are seen for both foods and nutrients. The data analysis was financially supported by the Health Insurance Fund.


Trends in the Canadian Surgery Forum (CSF): analysis of the CSF program over the past decade.
Numerous clinical and basic science-related innovations have been presented at the Canadian Surgery Forum (CSF). We sought to define changes in both the content and methodology of the CSF scientific program over the past decade. While the total volume of CSF abstract presentations has increased dramatically, the methodological quality has remained static, with few randomized trials and minimal prospective work. Although the majority of the scientific content is associated with urban university centres, the program also encourages content from community practices. Surgical education, hepatopancreatobiliary and bariatric content have increased substantially, but remain secondary to colorectal diseases.


Trends in Suicide by Level of Urbanization - United States, 1999-2015.
Suicide is a major and continuing public health concern in the United States. During 1999-2015, approximately 600,000 U.S. residents died by suicide, with the highest annual rate occurring in 2015 (1). Annual county-level mortality data from the National Vital Statistics System (NVSS) and annual county-level population data from the U.S. Census Bureau were used to analyze suicide rate trends during 1999-2015, with special emphasis on comparing more urban and less urban areas. U.S. counties were grouped by level of urbanization using a six-level classification scheme. To evaluate rate trends, joinpoint regression methodology was applied to the time-series data for each level of urbanization. Suicide rates significantly increased over the study period for all county groupings and accelerated significantly in 2007-2008 for the medium metro, small metro, and non-metro groupings. Understanding suicide trends by urbanization level can help identify geographic areas of highest risk and focus prevention efforts. Communities can benefit from implementing policies, programs, and practices based on the best available evidence regarding suicide prevention and key risk factors. Many approaches are applicable regardless of urbanization level, whereas certain strategies might be particularly relevant in less urban areas affected by difficult economic conditions, limited access to helping services, and social isolation.


The thermal sense of blood-sucking insects: why physics matters.
Blood-sucking arthropods exploit multimodal information for locating and recognising potential hosts. The heat emitted by the body of endothermic vertebrates constitutes a major cue for orientation. To exploit it in a reliable way, insects must be able to deal with two variants of thermal information, that is heat exchange and temperature fluctuations. Evaluating whether or not an object qualifies as a host by its temperature requires solving thermodynamic ambiguities in a context where temperature increase at the receptor level is just one, yet insufficient, piece of information. To be exploitable, this piece of information needs to be integrated with other variables. Here, I discuss the physical constraints associated to thermal orientation, as well as the way different blood-sucking insects acquire and make use of heat to recognise a host.


Body temperature elevation during exercise is essential for activating the Akt signaling pathway in the skeletal muscle of type 2 diabetic rats.
This study examined the effect of changes in body temperature during exercise on signal transduction-related glucose uptake in the skeletal muscle of type 2 diabetic rats. Otsuka Long-Evans Tokushima Fatty rats (25 weeks of age), which have type 2 diabetes, were divided into the following four weight-matched groups; control (CON, n = 6), exercised under warm temperature (WEx, n = 8), exercised under cold temperature (CEx, n = 8), and heat treatment (HT, n = 6). WEx and CEx animals were subjected to running on a treadmill at 20 m/min for 30 min under warm (25°C) or cold (4°C) temperature. HT animals were exposed to single heat treatment (40-41°C for 30 min) in a heat chamber. Rectal and muscle temperatures were measured immediately after exercise and heat treatment, and the gastrocnemius muscle was sampled under anesthesia. Rectal and muscle temperatures increased significantly in rats in the WEx and HT, but not the CEx, groups. The phosphorylation levels of Akt, AS160, and TBC1D1 (Thr590) were significantly higher in the WEx and HT groups than the CON group (p < 0.05). In contrast, the phosphorylation levels of AMP-activated protein kinase, ACC, and TBC1D1 (Ser660) were significantly higher in rats in the WEx and CEx groups than the CON group (p < 0.05) but did not differ significantly between rats in the WEx and CEx groups. Body temperature elevation by heat treatment did not activate the AMPK signaling. Our data suggest that body temperature elevation during exercise is essential for activating the Akt signaling pathway in the skeletal muscle of rats with type 2 diabetic rats.


A simple method for the isolation of adrenal chromaffin granules on a large scale.
Highly purified chromaffin granules can be obtained from homogenates of either ox, pig, horse or rat adrenal medullae by ultracentrifugation of the large-granule fraction layered on 1.6m-sucrose solution, by using angle-head rotors. The chromaffin granules are obtained as a pink sediment that is only slightly contaminated by mitochondria and lysosomes.


Expression of platelet-endothelial cell adhesion molecule-1 in human umbilical vein endothelial cells by exposure to advanced glycosylation end products and inflammatory mediators.
To determine whether advanced glycosylation end products modified bovine serum albumin (AGEs-BSA) affects endothelial cell lateral junction protein, platelet-endothelial cell adhesion molecule-1 (PECAM-1) in the presence or absence of inflammatory mediators. Cultured human umbilical vein endothelial cells (HUVECs) were exposed to AGEs-BSA for 6, 12, 24, and 36 hours, and exposed to AGEs-BSA glycosylated with different concentrations of glucose, tumor necrosis factor-alpha (TNF-alpha), interferon (IFN-gamma), TNF-alpha + IFN-gamma and AGEs-BSA + TNF-alpha for 24 hours, respectively. Expression of PECAM-1 mRNA was measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) with beta-actin as an internal standard, and sequencing of RT-PCR products was performed to confirm the specificity of amplification for PECAM-1 gene. The endothelial cell surface expression of PECAM-1 was determined by flow cytometry (FCM). There were no significant changes in the expression of PECAM-1 mRNA and protein when the cells were exposed to AGEs-BSA with different concentrations or periods (P > 0.05). However, PECAM-1 expression was reduced in the cells treated with TNF-alpha, IFN-gamma, TNF-alpha + IFN-gamma and AGEs-BSA + TNF-alpha. The level of PECAM-1 treated with AGEs-BSA + TNF-alpha was lower than that of TNF-alpha treated alone (P < 0.01). AGEs-BSA had no effect on the expression of PECAM-1 mRNA and protein in cultured HUVEC. With the presence of inflammatory mediator TNF-alpha, AGEs-BSA decreased the level of PECAM-1, which might reduce the adhesion interaction between adjacent endothelial cells, enhance the permeability of endothelial cells, and might be implicated in the endothelial dysfunction and pathogenesis of atherosclerosis in patients with diabetes mellitus. The significance of this phenomenon in intracellular signal transduction remains to be determined.


Approaches to CNS Drug Delivery with a Focus on Transporter-Mediated Transcytosis.
Drug delivery to the central nervous system (CNS) conferred by brain barriers is a major obstacle in the development of effective neurotherapeutics. In this review, a classification of current approaches of clinical or investigational importance for the delivery of therapeutics to the CNS is presented. This classification includes the use of formulations administered systemically that can elicit transcytosis-mediated transport by interacting with transporters expressed by transvascular endothelial cells. Neurotherapeutics can also be delivered to the CNS by means of surgical intervention using specialized catheters or implantable reservoirs. Strategies for delivering drugs to the CNS have evolved tremendously during the last two decades, yet, some factors can affect the quality of data generated in preclinical investigation, which can hamper the extension of the applications of these strategies into clinically useful tools. Here, we disclose some of these factors and propose some solutions that may prove valuable at bridging the gap between preclinical findings and clinical trials.


Product study of the OH, NO3, and O3 initiated atmospheric photooxidation of propyl vinyl ether.
A product study is reported on the gas-phase reactions of OH and NO3 radicals and ozone with propyl vinyl ether (PVE). The experiments were performed in a 405 L borosilicate glass chamber in synthetic air at 298 +/- 3 K using long path in situ FTIR spectroscopy for the analysis of the reactants and products. In the presence of NO(x) (NO + NO2) the main products for the OH-radical initiated oxidation of PVE were propylformate and formaldehyde with molar formation yields of 78.6 +/- 8.8% and 75.9 +/- 8.4%, respectively. In the absence of NO(x) propylformate and formaldehyde were formed with molar formation yields of 63.0 +/- 9.0% and 61.3 +/- 6.3%, respectively. In the reaction of NO3 radicals with PVE propylformate 52.7 +/- 5.9% and formaldehyde 55.0 +/- 6.3% were again observed as major products. The ozonolysis of PVE led to the production of propylformate, formaldehyde, hydroxyperoxymethyl formate (HPMF; HC(O)OCH2OOH), and CO with molar formation yields of 89.0 +/- 11.4%, 12.9 +/- 4.0%, 13.0 +/- 3.4%, and 10.9 +/- 2.6%, respectively. The formation yield of OH radicals in the ozonolysis of PVE was estimated to be 17 +/- 9%. Simple atmospheric degradation mechanisms are postulated to explain the formation of the observed products.


Comparative analysis of the efficacy of astigmatic correction after wavefront-guided and wavefront-optimized LASIK in low and moderate myopic eyes.
To evaluate and compare the efficacy of the astigmatic correction achieved with laser in situ keratomileusis (LASIK) in eyes with myopic astigmatism using wavefront-guided (WFG) and wavefront-optimized (WFO) ablation profiles. Prospective study included 221 eyes undergoing LASIK: 99 and 122 eyes with low and moderate myopic astigmatism (low and moderate myopia groups). Two subgroups were differentiated in each group according to the ablation profile: WFG subgroup, 109 eyes (45/64, low/moderate myopia groups) treated using the Advanced CustomVue platform (Abbott Medical Optics Inc.), and WFO subgroup, 112 eyes (54/58, low/moderate myopia groups) treated using the EX-500 platform (Alcon). Clinical outcomes were evaluated during a 6-month follow-up, including a vector analysis of astigmatic changes. Significantly better postoperative uncorrected visual acuity and efficacy index was found in the WFG subgroups of each group (P≤0.041). Postoperative spherical equivalent and cylinder were significantly higher in WFO subgroups (P≤0.003). In moderate myopia group, a higher percentage of eyes with a postoperative cylinder ≤0.25 D was found in the WFG subgroup (90.6% vs 65.5%, P=0.002). In low and moderate myopia groups, the difference vector was significantly higher in the WFO subgroup compared to WFG (P<0.001). In moderate myopia group, the magnitude (P=0.008) and angle of error (P<0.001) were also significantly higher in the WFO subgroup. Significantly less induction of high order aberrations were found with WFG treatments in both low and moderate myopia groups (P≤0.006). A more efficacious correction of myopic astigmatism providing a better visual outcome is achieved with WFG LASIK compared to WFO LASIK.


Growth of the lateral tunnel in patients who underwent a total cavopulmonary connection at less than 5 years of age.
A lateral tunnel-total cavopulmonary connection (LT-TCPC) using a right atrial (RA) free wall is the first choice of treatment for patients with a small body weight in this institute. Whether the growth of the LT is appropriate or not according to the growth of the body remains controversial. In addition, the optimal initial diameter of an LT is unknown. The purpose of this study was to verify the growth of the LT. Ninety-one patients of a total of 267 TCPC cases underwent an LT-TCPC at less than 5 years of age in this institute between March 1991 and June 2008. The data on 47 of the 91 patients, which were available to investigate the LT growth, were retrospectively reviewed. The mean age at LT-TCPC was 37+/-11 months (16-57 months). The mean body weight at TCPC was 12.4+/-2.4 kg (7.6-20.0 kg). The initial LT diameter was determined with Hegar's sizer of the estimated half-pulmonary arterial (PA) diameter, which is a diameter that results in half of the dimension of the normal pulmonary valve. The measured maximum LT diameter (mm) divided by the estimated half-PA diameter (mm) was considered as the LT index. The size of the LT was evaluated using either echocardiography or angiography. The mean follow-up period was 7.4+/-3.5 years (1.6-13.5 years). The LT index was initially 2.0+/-0.7 (1.3-4.5), 2.0+/-0.4 (1.3-3.2) at 1 year after operation, 2.1+/-0.5 (1.5-3.2) at 5 years after operation, 1.9+/-0.4 (1.5-2.8) at 10 years after operation and 2.1+/-0.5 (1.6-2.5) at 13 years after operation, respectively. LT growth suitable for the body growth can be expected. Although there was some variation in the initial LT diameter, the LT index tended to converge at 2.0 with growth.


Combating severe malaria in African children.
An initiative to reduce childhood mortality due to malaria, diarrhoea and vaccine-preventable diseases, called the Africa Child Survival Initiative-Combatting Childhood Communicable Diseases (CCCD) project, was started in 1982 and is now operating in 13 African countries, 12 of which are endemic for malaria. The project's malaria control strategy relies on the use of drugs, mainly chloroquine, to prevent severe illness and death in children less than 5 years of age; chemoprophylaxis for pregnant women is also advised to prevent low birth weight in newborns. The strategy is based on WHO recommendations which focus on improved diagnosis and treatment of cases and chemoprophylaxis for pregnant women.In 9 out of the 13 CCCD countries the sensitivity of Plasmodium falciparum to chloroquine in children was investigated and a drug sensitivity surveillance network was established. In areas with chloroquine-resistant P. falciparum, treatment with chloroquine was found to decrease the temperature in febrile children and to greatly reduce the parasite density, thus preventing severe illness and possible death. Baseline surveys in 6 countries have shown a wide range of treatment practices, e.g., use of chloroquine in various doses without standard guidelines and the excessive use of quinine and chloroquine injections in some health units. As pregnant women are often not taking chemoprophylaxis, research has been started on alternative approaches to drug treatment to prevent the adverse effects of malaria on the fetus.Only 4 of the 12 malarious countries had malaria control units when their CCCD programme began and these were concerned mainly with vector control issues; 11 of 12 countries now have such units and a written CCCD malaria plan. These countries have now integrated malaria control activities into primary health care and have begun to implement standardized treatment and prevention practices that are described in their national CCCD malaria plans.


Total knee arthroplasty in younger patients: a 13-year follow-up study.
Total knee arthroplasty (TKA) is a well-established treatment at the end stage of a degenerated knee joint. This operative treatment generally relieves pain, improves physical function, and has a high level of patient satisfaction, especially in the elderly. Younger patients, however, are demanding and have a higher level of physical activity compared to elderly patients. One could therefore expect more mechanical problems such as prosthetic loosening and polyethylene wear after long-term follow-up. The goal of this retrospective cohort study was to determine the survival and long-term results of TKA in young patients. Patients who received a TKA at age 60 years or younger for any reason were included. Minimum follow-up was 10 years. Thirty-nine TKAs (Anatomic Graduate Components; Biomet, Warsaw, Indiana) in 31 patients were included. Average patient age was 52.6 years. There were 3 revisions because of infection; in 1 knee the patella was revised because of aseptic loosening. After an average 13-year follow-up, the survival rate was 89.7% and function scores showed a reasonably functioning TKA. There was no difference in survival rate and function scores between patients with rheumatoid arthritis and those with primary or secondary (posttraumatic) osteoarthritis. Our experience with TKA in a younger patient population has been encouraging. The risk of loosening and wear of the implant in our study is low, and this type of TKA also seems to be an effective and safe treatment for younger patients.


Justifications for Non-Consensual Medical Intervention: From Infectious Disease Control to Criminal Rehabilitation.
A central tenet of medical ethics holds that it is permissible to perform a medical intervention on a competent individual only if that individual has given informed consent to the intervention. Yet it occasionally seems morally permissible to carry out non-consensual medical interventions on competent individuals for the purpose of infectious disease control (IDC). We describe two different moral frameworks that have been invoked in support of non-consensual IDC interventions and identify five desiderata that might be used to guide assessments of the moral permissibility of such interventions on either kind of fundamental justification. We then consider what these desiderata imply for the justifiability of carrying out non-consensual medical interventions that are designed to facilitate rehabilitation amongst serious criminal offenders. We argue that these desiderata suggest that a plausible case can be made in favor of such interventions.


Detection of heterozygous nonsense mutations in genes of interest using an Escherichia coli-based stop codon assay.
Since nonsense mutations are closely associated with severe conditions of genetic disorders, including familial cancers, rapid and precise detection of those mutations is very important for research purposes and molecular diagnosis. Currently, screening methods such as the FASAY (functional analysis of separated alleles in yeast) and the Y-SC (stop codon assay in yeast) are used for functional detection of nonsense mutations in genes of interest. But these yeast-based approaches are time-consuming, expensive and complicated. In order to circumvent these problems, we, in the present study, devised a novel Escherichia coli-based screening method, the E-SC (E. coli stop codon assay) for the detection of heterozygous nonsense mutations in genes of interest. Our strategy was based on the fact that the plasmid replicating with a low copy number in E. coli allows an effective separation of normal and mutant alleles. Moreover, it relies on the expression vector, resulting in the formation of white and blue colonies for mutant and normal alleles through the expression of PCR-amplified fragment/lacZ fusion protein respectively. To evaluate the applicability of the E-SC method for the detection of the heterozygous truncating mutation, PCR-amplified exon 7 of the StAR [steroidogenic acute regulatory protein; causative gene of the CAH (congenital lipoid adrenal hyperplasia)] and RT (reverse transcription)-PCR-amplified full-length cDNA of MeCP2 (methyl-CpG-binding protein 2; causative gene of Rett syndrome) were used. The E-SC showed an almost 1:1 ratio of blue/white colonies in all patients examined, whereas the control samples produced blue colonies only. These results demonstrate that the E-SC system is useful for rapid and precise detection of known and unknown heterozygous truncation mutations in genes that cause genetic disorders and familial cancers.


Carotid Artery Stiffness: Imaging Techniques and Impact on Cerebrovascular Disease.
Arterial stiffness is an important measure of vascular aging and atherosclerosis. Though it is measured in many well-known epidemiologic cohort studies, arterial stiffness is often overlooked in routine clinical practice for a number of reasons including difficulties in measurement, variations in definition, and uncertainties surrounding treatment. Central arterial stiffness, a surrogate for aortic stiffness, is the most commonly measured marker of arterial stiffness. In addition to central stiffness, there are also a number of ultrasound based techniques to measure local vascular stiffness, including carotid stiffness. There is evidence that both local carotid stiffness and central arterial stiffness measures are associated with multiple cerebrovascular processes, including stroke and cognitive dysfunction. Mechanistic explanations supporting this association include increased flow load experienced by the cerebral microvasculature leading to cerebral parenchymal damage. In this article, we review definitions of carotid artery stiffness measures and pathophysiologic mechanisms underpinning its association with plaque development and downstream cerebral pathology. We will review the evidence surrounding the association of carotid stiffness measures with downstream manifestations including stroke, cerebral small vessel disease detected on brain MR such as white matter hyperintensities and covert brain infarctions, brain atrophy, and cognitive dysfunction. With consistent definitions, measurement methods, and further scientific support, carotid stiffness may have potential as an imaging-based risk factor for stroke and cognitive decline.


An Unusual Coexistence of Primary Central Nervous System Non-Hodgkin's Lymphoma and Acute Promyelocytic Leukemia.
Acute promyelocytic leukemia and primary central nervous system lymphoma are uncommon hematological malignancies. The co-occurrence of acute myeloid leukemia with various lymphoproliferative diseases is an extremely rare condition, especially in the absence of previous chemotherapy or radiotherapy. Herein, we provide a comprehensive characterization of a patient with concomitant diagnosis of extranodal high-grade non-Hodgkin B-cell neoplasm confined to the central nervous system and acute promyelocytic leukemia. We describe the efficacy and feasibility of the consecutive use of all-trans retinoic acid and arsenic trioxide-containing regimen for the treatment of promyelocytic leukemia and high-dose methotrexate plus cytarabine to treat lymphoproliferative involvement of the central nervous system.


Elevated blood pressures in obese young men with mild hypertension are sustained during the day and night.
The major goal of this study was to determine if the elevated blood pressures in obese men < 45 years old with mild hypertension persist outside the clinic. A secondary aim was to determine if hyperinsulinemia is associated with accentuated diurnal changes of blood pressure. To address these objectives, the clinic and ambulatory blood pressures as well as a 75-g, 2-h oral glucose tolerance test measurements were obtained from 9 lean normotensive, 9 lean hypertensive, and 22 obese hypertensive men < 45 years old. The week before study, volunteers ate an isocaloric diet with 220 mEq of NaCl/day. Obese hypertensives, subdivided by high (n = 11) and low (n = 11) insulin areas-under-the-curve (AUCs) in response to oral glucose, and lean hypertensives maintained higher ambulatory blood pressure than lean normotensives (130 +/- 3/74 +/- 1, 136 +/- 4/78 +/- 2, 132 +/- 5/77 +/- 3 v 118 +/- 4/65 +/- 2 mm Hg, respectively, P < .05). As expected, the insulin AUC during the glucose tolerance test was higher in obese hypertensives with higher insulin AUCs than in obese hypertensives with lower insulin AUCs, lean hypertensives, or lean normotensives (13.9 +/- 1.2 v 7.9 +/- 0.3, 7.2 +/- 0.7, 5.7 +/- 0.7 mU-min/dL, P < .05). Insulin AUCs were not significantly different in obese hypertensives with lower insulin levels, lean hypertensives, or lean normotensives. The diurnal increases of systolic and diastolic blood pressure as well as heart rate and pressure-rate product were similar in all four groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Magnetic field measurements via visible spectroscopy on the Z machine.
Sandia's Z Machine uses its high current to magnetically implode targets relevant to inertial confinement fusion. Since target performance is highly dependent on the applied drive field, measuring magnetic field at the target is essential for accurate simulations. Recently, the magnetic field at the target was measured through splitting of the sodium 3s-3p doublet at 5890 and 5896 Å. Spectroscopic dopants were applied to the exterior of the target, and spectral lines were observed in absorption. Magnetic fields in excess of 200 T were measured, corresponding to drive currents of approximately 5 MA early in the pulse.


Clinical settings in pseudomembranous colitis.
Renewed interest in pseudomembranous colitis (PMC) has occurred in recent years due to an increased incidence following the introduction of the antibiotics clindamycin and lincomycin. However, the disease was well known before the antibiotic era. In this paper the histopathological features are reemphasised and the similarity to early amoebic colitis is stressed. From a background of 32 patients, some unusual clinical settings are described. These consist of an association with renal transplantation; the demonstration of the lesion on the mucosal surface of rectal polypi and metaplastic bladder mucosa; its occurrence in an area of isolated ileum presenting as a "blind loop syndrome"; and examples suggesting that this disease can exist for quite long periods of time or may recur several times in the same patient.


[Thoracoscopy versus thoracotomy. The dilemma of the comparison and its meaning for quality assurance in thoracic surgery].
The need for scientific investigation into the benefits of thoracoscopy in comparison to thoracotomy as well as State intervention to assure quality in the field of surgery motivated the members of the commission of endoscopic surgery of the German Society of Thoracic Surgery to conduct a pilot project at their hospitals. This pilot project was expected to analyse data on the outcome and a selection of variables concerning trauma and postoperative quality of life of some 400 patients treated between 8/95 and 10/95 at 5 thoracic surgical clinics. On completion of the pilot project the course of 141 patients undergoing different thoracic operations at 4 thoracic surgery departments had been documented to various degrees. 60 patients for various indications received a thoracoscopy, 72 a thoracotomy. In 9 patients thoracoscopy was converted to thoracotomy (6.4%). Eight of the 141 patients died in the postoperative course (5.7%), overall morbidity was 15.6%. There was a slight but statistically not significant difference concerning mortality and morbidity in favor of thoracoscopy (1.7 vs. 9.7% and 10 vs. 19.4%). But, there was a selection of malignant diseases, higher age and high risk patients towards thoracotomy. In subgroups of patients undergoing operations not bigger than the resection of three lung wedges only time of operation and length of incision revealed to be significantly shorter for thoracoscopy (69(25-190) min vs. 128(24-240)min, p = 0.0013; 6(4-8)cm vs. 23(12-35)cm, p = 0.0001). Borderline significance was reached by the Spitzer-Index in advantage for thoracoscopy (8(2-10)points vs. 7(0-10)points, p = 0.0728). Thoracotomy and thoracoscopy are access procedures used with different indications in different patients. Differences concerning trauma and quality of life if present are marginal and will need studies to be outlined. Quality assurance in thoracic surgery using a standardized documentation will not succeed under the given circumstances.


Assessment of the flexibility of elite athletes using the modified Thomas test.
To analyse the modified Thomas test and obtain measures of flexibility for the iliopsoas, quadriceps and tensor fascia lata/iliotibial band. The modified Thomas test was used to determine the range of flexibility of 117 elite athletes in tennis, basketball, rowing, and running. The study has provided objective data for a clinical test measuring flexibility of the iliopsoas, quadriceps, and tensor fascia lata/iliotibial band. It is recommended that sufficient flexibility is obtained to perform a specific sport and that asymmetries between limbs are addressed.


Temperature dependence of the functional response.
The Arrhenius equation has emerged as the favoured model for describing the temperature dependence of consumption in predator-prey models. To examine the relevance of this equation, we undertook a meta-analysis of published relationships between functional response parameters and temperature. We show that, when plotted in lin-log space, temperature dependence of both attack rate and maximal ingestion rate exhibits a hump-shaped relationship and not a linear one as predicted by the Arrhenius equation. The relationship remains significantly downward concave even when data from temperatures above the peak of the hump are discarded. Temperature dependence is stronger for attack rate than for maximal ingestion rate, but the thermal optima are not different. We conclude that the use of the Arrhenius equation to describe consumption in predator-prey models requires the assumption that temperatures above thermal optima are unimportant for population and community dynamics, an assumption that is untenable given the available data.


Maternal Prepregnancy BMI and Glucose Level at 24-28 Gestational Weeks on Offspring's Overweight Status within 3 Years of Age.
Objective. To examine the relative impact of maternal prepregnancy body mass index (BMI) and glucose level at 24-28 gestational weeks on offspring's overweight status from birth to 3 years of age in China. Methods. Health care records of 21,354 mother-child pairs were collected. The single and joint associations of maternal prepregnancy BMI and glucose level at 24-28 gestational weeks with 0-3-year-old offspring's overweight status were assessed. Results. The odds ratios (95% confidence intervals) of offspring's macrosomia at birth and overweight/obesity at the 12th month, 24th month, and 36th month were 1.12 (1.11-1.13), 1.05 (1.04-1.06), 1.07 (1.06-1.08), and 1.11 (1.10-1.12) for each 1-unit increase (km/m2) in maternal prepregnancy BMI and 1.13 (1.10-1.17), 1.01 (0.99-1.03), 0.99 (0.96-1.01), and 1.00 (0.97-1.02) for each 1-unit increase (mmol/L) in maternal glucose level at 24-28 gestational weeks, respectively. The positive association of maternal glucose level with macrosomia at birth was similar between prepregnancy normal weight (BMI < 24 kg/m2) and overweight (BMI ≥ 24 kg/m2); however, the positive association of high maternal glucose level with childhood overweight was only seen among prepregnancy normal weight mothers but not among overweight mothers. Conclusions. The impact of maternal gestational hyperglycemia on offspring's overweight before 3 years of age can be modified by prepregnancy BMI.


Validation of real-time inside-out tracking and depth realization technologies for augmented reality-based neuronavigation.
Concomitant with the significant advances in computing technology, the utilization of augmented reality-based navigation in clinical applications is being actively researched. In this light, we developed novel object tracking and depth realization technologies to apply augmented reality-based neuronavigation to brain surgery. We developed real-time inside-out tracking based on visual inertial odometry and a visual inertial simultaneous localization and mapping algorithm. The cube quick response marker and depth data obtained from light detection and ranging sensors are used for continuous tracking. For depth realization, order-independent transparency, clipping, and annotation and measurement functions were developed. In this study, the augmented reality model of a brain tumor patient was applied to its life-size three-dimensional (3D) printed model. Using real-time inside-out tracking, we confirmed that the augmented reality model remained consistent with the 3D printed patient model without flutter, regardless of the movement of the visualization device. The coordination accuracy during real-time inside-out tracking was also validated. The average movement error of the X and Y axes was 0.34 ± 0.21 and 0.04 ± 0.08 mm, respectively. Further, the application of order-independent transparency with multilayer alpha blending and filtered alpha compositing improved the perception of overlapping internal brain structures. Clipping, and annotation and measurement functions were also developed to aid depth perception and worked perfectly during real-time coordination. We named this system METAMEDIP navigation. The results validate the efficacy of the real-time inside-out tracking and depth realization technology. With these novel technologies developed for continuous tracking and depth perception in augmented reality environments, we are able to overcome the critical obstacles in the development of clinically applicable augmented reality neuronavigation.


Stokes phenomena in discrete Painlevé II.
We consider the asymptotic behaviour of the second discrete Painlevé equation in the limit as the independent variable becomes large. Using asymptotic power series, we find solutions that are asymptotically pole-free within some region of the complex plane. These asymptotic solutions exhibit Stokes phenomena, which is typically invisible to classical power series methods. We subsequently apply exponential asymptotic techniques to investigate such phenomena, and obtain mathematical descriptions of the rapid switching behaviour associated with Stokes curves. Through this analysis, we determine the regions of the complex plane in which the asymptotic behaviour is described by a power series expression, and find that the behaviour of these asymptotic solutions shares a number of features with the tronquée and tri-tronquée solutions of the second continuous Painlevé equation.


Novel Approach for In Vivo Detection of Vulnerable Coronary Plaques Using Molecular 3-T CMR Imaging With an Albumin-Binding Probe.
This study sought to investigate the potential of the noninvasive albumin-binding probe gadofosveset-enhanced cardiac magnetic resonance (GE-CMR) for detection of coronary plaques that can cause acute coronary syndromes (ACS). ACS are frequently caused by rupture or erosion of coronary plaques that initially do not cause hemodynamically significant stenosis and are therefore not detected by invasive x-ray coronary angiography (XCA). A total of 25 patients with ACS or symptoms of stable coronary artery disease underwent GE-CMR, clinically indicated XCA, and optical coherence tomography (OCT) within 24 h. GE-CMR was performed approximately 24 h following a 1-time application of gadofosveset-trisodium. Contrast-to-noise ratio (CNR) was quantified within coronary segments in comparison with blood signal. A total of 207 coronary segments were analyzed on GE-CMR. Segments containing a culprit lesion in ACS patients (n = 11) showed significant higher signal enhancement (CNR) following gadofosveset-trisodium application than segments without culprit lesions (n = 196; 6.1 [3.9 to 16.5] vs. 2.1 [0.5 to 3.5]; p < 0.001). GE-CMR was able to correctly identify culprit coronary lesions in 9 of 11 segments (sensitivity 82%) and correctly excluded culprit coronary lesions in 162 of 195 segments (specificity 83%). Additionally, segmented areas of thin-cap fibroatheroma (n = 22) as seen on OCT demonstrated significantly higher CNR than segments without coronary plaque or segments containing early atherosclerotic lesions (n = 185; 9.2 [3.3 to 13.7] vs. 2.1 [0.5 to 3.4]; p = 0.001). In this study, we demonstrated for the first time the noninvasive detection of culprit coronary lesions and thin-cap fibroatheroma of the coronary arteries in vivo by using GE-CMR. This method may represent a novel approach for noninvasive cardiovascular risk prediction.


Proposal of a robust measurement scheme for the nonadiabatic spin torque using the displacement of magnetic vortices.
A spin-polarized current traversing a ferromagnet with continuously varying magnetization exerts a torque on the magnetization. The nonadiabatic contribution to this spin-transfer torque is currently under strong debate, as its value differs by orders of magnitude in theoretical predictions and in measurements. Here, a measurement scheme is presented that allows us to determine the strength of the nonadiabatic spin torque accurately and directly. Analytical and numerical calculations show that the scheme is robust against the uncertainties of the exact current direction and Oersted fields.


[Oral load test with beta-carotene in normal and dysthyroid subjects].
An oral load of beta-carotene (500 mg) was administered to four normal, four hypo and four hyperthyroid subjects. Plasma beta-carotene content was determined at the 2nd, 4th, 6th, 8th, 10th, 12th and 24th hour after administration and at every 24th hour thereafter for 5 consecutive days. Plasma assays were performed by HPLC. No significant differences were revealed by Student's T test for one group to the other. The authors sustain that, as there is no impairment in intestinal uptake of beta-carotene in disthyroid subjects, the elsewhere described increase in carotinemia in hypothyroids is due to other mechanisms.


Comparison of Virtual Nutri Plus® and Dietpro 5i® software systems for the assessment of nutrient intake before and after Roux-en-Y gastric bypass.
The assessment of nutritional intake before and after bariatric surgery assists in identifying eating disorders, nutritional deficiencies and weight loss/maintenance. The 7-day record is the gold standard for such an assessment and is interpreted using specialized software. This study sought to compare the Virtual Nutri Plus® and Dietpro 5i® software systems in assessing nutrient intake in obese patients with type 2 diabetes mellitus who underwent a Roux-en-Y gastric bypass. Nutritional intake was assessed in 10 obese women with type 2 diabetes mellitus before and 3 months after Roux-en-Y gastric bypass. The 7-day record was used to assess food intake and then, the Virtual Nutri Plus® and Dietpro 5i® software systems were used to calculate calorie, macronutrient and micronutrient intake based on validated food chemical composition databases. Clinicaltrials.gov: NCT01251016. During the preoperative period, deficits in the ingestion of total fiber and 15 out of 22 estimated micronutrients were observed when using the Virtual Nutri Plus®, compared to deficiencies in total fiber and 4 micronutrients when using the Dietpro 5i®. During the postoperative period, both the Virtual Nutri Plus® and Dietpro 5i® systems detected deficits in the ingestion of total fiber, carbohydrates and 19 micronutrients, but only the Virtual Nutri Plus® detected deficits in complex B vitamins (except B12) and minerals. Virtual Nutri Plus® was more sensitive than Dietpro 5i® for the identification of deficits in nutrient intake in obese, type 2 diabetes mellitus patients undergoing Roux-en-Y gastric bypass.


Overview of emerging nonvolatile memory technologies.
Nonvolatile memory technologies in Si-based electronics date back to the 1990s. Ferroelectric field-effect transistor (FeFET) was one of the most promising devices replacing the conventional Flash memory facing physical scaling limitations at those times. A variant of charge storage memory referred to as Flash memory is widely used in consumer electronic products such as cell phones and music players while NAND Flash-based solid-state disks (SSDs) are increasingly displacing hard disk drives as the primary storage device in laptops, desktops, and even data centers. The integration limit of Flash memories is approaching, and many new types of memory to replace conventional Flash memories have been proposed. Emerging memory technologies promise new memories to store more data at less cost than the expensive-to-build silicon chips used by popular consumer gadgets including digital cameras, cell phones and portable music players. They are being investigated and lead to the future as potential alternatives to existing memories in future computing systems. Emerging nonvolatile memory technologies such as magnetic random-access memory (MRAM), spin-transfer torque random-access memory (STT-RAM), ferroelectric random-access memory (FeRAM), phase-change memory (PCM), and resistive random-access memory (RRAM) combine the speed of static random-access memory (SRAM), the density of dynamic random-access memory (DRAM), and the nonvolatility of Flash memory and so become very attractive as another possibility for future memory hierarchies. Many other new classes of emerging memory technologies such as transparent and plastic, three-dimensional (3-D), and quantum dot memory technologies have also gained tremendous popularity in recent years. Subsequently, not an exaggeration to say that computer memory could soon earn the ultimate commercial validation for commercial scale-up and production the cheap plastic knockoff. Therefore, this review is devoted to the rapidly developing new class of memory technologies and scaling of scientific procedures based on an investigation of recent progress in advanced Flash memory devices.


[Antibody engineering-based approach for hapten immunometric assays with high sensitivity].
The trace characterization of physiologically active substances with low molecular weight (e.g., steroids, catecholamines, prostaglandins, and oligopeptides), which are classified as "haptens", is an important subject in clinical analysis, and competitive immunoassays have conventionally been used for this purpose. However, the subfemtomole-range determination of haptens is very difficult, as the sensitivity of competitive immunoassays is essentially limited by the affinity of the anti-hapten antibodies that barely reaches the range of 10(11) (l/mol) as the affinity constant (K(a)). Although a noncompetitive "immunometric assay" format, the two-site immunometric assay (sandwich immunoassay), enables even subattomole-range measurements of macromolecules such as proteins, this principle can not be directly applied to haptens, as their low molecular mass prohibits simultaneous binding by two antibody molecules. To overcome such limitations, we are required either to create artificial antibodies showing ultrahigh affinity to haptens by protein engineering of antibody molecules ("antibody engineering") or establishment of novel immunometric assay formats applicable to haptens. This review surveys the background and recent approach for subfemtomole-range determination of haptens using novel immunometric assay methods. Our studies for the development of hapten immunometric assays are also described.


Initial reaction(s) in biotransformation of CL-20 is catalyzed by salicylate 1-monooxygenase from Pseudomonas sp. strain ATCC 29352.
CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane) (C(6)H(6)N(12)O(12)), a future-generation high-energy explosive, is biodegradable by Pseudomonas sp. strain FA1 and Agrobacterium sp. strain JS71; however, the nature of the enzyme(s) involved in the process was not understood. In the present study, salicylate 1-monooxygenase, a flavin adenine dinucleotide (FAD)-containing purified enzyme from Pseudomonas sp. strain ATCC 29352, biotransformed CL-20 at rates of 0.256 +/- 0.011 and 0.043 +/- 0.003 nmol min(-1) mg of protein(-1) under anaerobic and aerobic conditions, respectively. The disappearance of CL-20 was accompanied by the release of nitrite ions. Using liquid chromatography/mass spectrometry in the negative electrospray ionization mode, we detected a metabolite with a deprotonated mass ion [M - H](-) at 345 Da, corresponding to an empirical formula of C(6)H(6)N(10)O(8), produced as a result of two sequential N denitration steps on the CL- 20 molecule. We also detected two isomeric metabolites with [M - H](-) at 381 Da corresponding to an empirical formula of C(6)H(10)N(10)O(10). The latter was a hydrated product of the metabolite C(6)H(6)N(10)O(8) with addition of two H(2)O molecules, as confirmed by tests using (18)O-labeled water. The product stoichiometry showed that each reacted CL-20 molecule produced about 1.7 nitrite ions, 3.2 molecules of nitrous oxide, 1.5 molecules of formic acid, and 0.6 ammonium ion. Diphenyliodonium-mediated inhibition of salicylate 1-monooxygenase and a comparative study between native, deflavo, and reconstituted enzyme(s) showed that FAD site of the enzyme was involved in the biotransformation of CL-20 catalyzed by salicylate 1-monooxygenase. The data suggested that salicylate 1-monooxygenase catalyzed two oxygen-sensitive single-electron transfer steps necessary to release two nitrite ions from CL-20 and that this was followed by the secondary decomposition of this energetic chemical.


Nuclear localization of the dehydrin OpsDHN1 is determined by histidine-rich motif.
The cactus OpsDHN1 dehydrin belongs to a large family of disordered and highly hydrophilic proteins known as Late Embryogenesis Abundant (LEA) proteins, which accumulate during the late stages of embryogenesis and in response to abiotic stresses. Herein, we present the in vivo OpsDHN1 subcellular localization by N-terminal GFP translational fusion; our results revealed a cytoplasmic and nuclear localization of the GFP::OpsDHN1 protein in Nicotiana benthamiana epidermal cells. In addition, dimer assembly of OpsDHN1 in planta using a Bimolecular Fluorescence Complementation (BiFC) approach was demonstrated. In order to understand the in vivo role of the histidine-rich motif, the OpsDHN1-ΔHis version was produced and assayed for its subcellular localization and dimer capability by GFP fusion and BiFC assays, respectively. We found that deletion of the OpsDHN1 histidine-rich motif restricted its localization to cytoplasm, but did not affect dimer formation. In addition, the deletion of the S-segment in the OpsDHN1 protein affected its nuclear localization. Our data suggest that the deletion of histidine-rich motif and S-segment show similar effects, preventing OpsDHN1 from getting into the nucleus. Based on these results, the histidine-rich motif is proposed as a targeting element for OpsDHN1 nuclear localization.


Virtual Screening for the Discovery of Microbiome β-Glucuronidase Inhibitors to Alleviate Cancer Drug Toxicity.
Despite the potency of most first-line anti-cancer drugs, nonadherence to these drug regimens remains high and is attributable to the prevalence of "off-target" drug effects that result in serious adverse events (SAEs) like hair loss, nausea, vomiting, and diarrhea. Some anti-cancer drugs are converted by liver uridine 5'-diphospho-glucuronosyltransferases through homeostatic host metabolism to form drug-glucuronide conjugates. These sugar-conjugated metabolites are generally inactive and can be safely excreted via the biliary system into the gastrointestinal tract. However, β-glucuronidase (βGUS) enzymes expressed by commensal gut bacteria can remove the glucuronic acid moiety, producing the reactivated drug and triggering dose-limiting side effects. Small-molecule βGUS inhibitors may reduce this drug-induced gut toxicity, allowing patients to complete their full course of treatment. Herein, we report the discovery of novel chemical series of βGUS inhibitors by structure-based virtual high-throughput screening (vHTS). We developed homology models for βGUS and applied them to large-scale vHTS against nearly 400,000 compounds within the chemical libraries of the National Center for Advancing Translational Sciences at the National Institutes of Health. From the vHTS results, we cherry-picked 291 compounds via a multifactor prioritization procedure, providing 69 diverse compounds that exhibited positive inhibitory activity in a follow-up βGUS biochemical assay in vitro. Our findings correspond to a hit rate of 24% and could inform the successful downstream development of a therapeutic adjunct that targets the human microbiome to prevent SAEs associated with first-line, standard-of-care anti-cancer drugs.


Middle-ear disease in Indians of the Mount Currie Reservation, British Columbia.
Complete otological examinations, including audiograms, were carried out on 504 British Columbia Indians of the Mount Currie Reservation. Of these, 79 were found to have evidence of current middle ear pathology, while 226 were known to have had previous disease. Among 364 subjects who could be formally tested, 112 had a 15-decibel or greater hearing loss in the speech frequencies. Among these Indians, middle-ear disease began early in life and recurrences were frequent. The prevalence of aural disease was related to poor social conditions, family history and presence of nasal discharge. No other relationships could be demonstrated, and there was no evident benefit from adenotonsillectomy. No secretory otitis or otosclerosis and almost no sensorineural high-tone hearing loss were discovered.


[A critical review of the pragmatic clinical trial].
Schwartz and Lellouch proposed in 1967 to differentiate between pragmatic and explanatory clinical trials. The pragmatic approach has been understood in different ways and has also been the object of some criticism. Yet different authors have asked to perform pragmatic clinical trials, especially in issues requiring a therapeutical decision. In order to clarify the present situation of the pragmatic trial, a bibliographic review has been performed. Between 1976 and 2002, 95 original articles on clinical trials conducted following a pragmatic design have been found. Only four followed strictly the approach developed by Schwartz et al. In a pragmatic clinical trial, it is usually not possible to blind the interventions and for this reason randomization is imperfect. This limitation casts doubts about the validity of the frequentistic methods in the intention-to-treat evaluation of the results of a pragmatic trial. This experimental approach demands an evaluation according to the decision-making theory. Following the Bayes theorem, the credibility and the previous probability of a hypothesis conditions its posterior probability. It has been agreed that Bayesian statistics is a suitable instrument for the evaluation of a pragmatic clinical trial, but the lack of adequate informatics' programs has limited seriously its application. Recently,some new programs (WinBUGS, TreeAge) have been developed and applied to the decision analysis in some primary care therapeutic questions. It seems possible to predict that, thanks to the new informatics'programs on Bayesian statistics, the pragmatic clinical trial will experience, in the short term, an important revival.


HIV-associated primary pulmonary hypertension: a first case report in Thailand and literature review.
A 32-year-old woman had asymptomatic HIV infection diagnosed with primary pulmonary hypertension simultaneously. She presented after a three-month rapid progression of symptoms and hemodynamic change. Physical examination and laboratory findings were compatible with pulmonary hypertension. No sensible cause could be found for the pulmonary hypertension except the HIV seropositivity; therefore, HIV-associated primary pulmonary hypertension was diagnosed. She was treated with diltiazem and oral anti-coagulation. After four months, her functional status improved from a NYHA functional class of II to I and improved in right venticular function. Since HIV is epidemic, the authors recommend HIV testing in cases of primary pulmonary hypertension.


Regioselective glucuronidation of gingerols by human liver microsomes and expressed UDP-glucuronosyltransferase enzymes: reaction kinetics and activity correlation analyses for UGT1A9 and UGT2B7.
To determine the reaction kinetics for regioselective glucuronidation of gingerols (i.e. 6-, 8- and 10-gingerol) by human liver microsomes and expressed UDP-glucuronosyltransferase (UGT) enzymes, and to identify the main UGT enzymes involved in regioselective glucuronidation of gingerols. The rates of glucuronidation were determined by incubating the gingerols with uridine diphosphoglucuronic acid-supplemented microsomes. Kinetic parameters were derived by fitting an appropriate model to the data. Activity correlation analyses were performed to identify the main UGT enzymes contributing to hepatic metabolism of gingerols. Glucuronidation at the 4'-OH group was much more favoured than that at 5-OH. The degree of position preference was compound-dependent; the catalytic efficiency ratios of 4'-O- to 5-O-glucuronidation were 9.1, 19.7 and 2.9 for 6-, 8- and 10-gingerol, respectively. UGT1A8 (an intestinal enzyme), UGT1A9 and UGT2B7 were the enzymes showing the highest activity towards gingerols. Formation of 5-O-glucuronide was mainly catalysed by UGT1A9. UGT2B7 was the only enzyme that generated glucuronides at both 4'-OH and 5-OH sites, although a strong position preference was observed with 4'-OH (≥80.2%). Further, activity correlation analyses indicated that UGT2B7 and UGT1A9 were primarily responsible for 4'-O-glucuronidation and 5-O-glucuronidation of gingerols in the liver, respectively. Gingerols were metabolized by multiple hepatic and gastrointestinal UGT enzymes. Also, UGT1A9 and 2B7 were the main contributors to regioselective glucuronidation of gingerols in the liver.


EXTERNAL AND INTERNAL EXPOSURE TO FUKUSHIMA RESIDENTS.
The Great East Japan Earthquake of 11 March 2011, caused the Fukushima Daiichi Nuclear Power Plant Accident, which resulted in the release of a large amount of radioactive materials into the environment, and there is a serious concern about the radiation effects on the health of residents living in the affected areas. The evaluation of exposure dose is fundamental for the estimation of health effects, and whenever possible, the exposure dose should be evaluated by actual measurements as opposed to estimations. Here, the outline of the exposure doses of residents estimated from surveys or obtained by measurements is described. Fukushima Health Management Survey reported the results for 460 408 residents during the first 4 months after the accident; 66.3% received doses <1 mSv, 94.9% received <2 mSv, 99.7% received <5 mSv and the maximum dose was 25 mSv. Thus, it was demonstrated that the results from personal dosemeter measurements were comparable to the estimations. The dose assessment of internal exposure of 184 205 residents conducted by Fukushima Prefecture by using whole body counter showed that 99.986% received <1 mSv, with the maximum dose being 3 mSv. Regarding exposure of the thyroid, there is not enough data for the Fukushima accident, but it is presumed that thyroid doses are much lower than those from Chernobyl. The outline of exposure doses of residents in result of the accident is still being clarified, questions and uncertainties in dose assessment remain and further efforts for more accurate dosimetry are required continuously.


Assessment of C-Shaped Canal Morphology in Mandibular and Maxillary Second Molars in an Iraqi Subpopulation Using Cone-Beam Computed Tomography.
Endodontic treatment is basically dependent on knowledge of the root canal anatomy. The goal of this study was to use cone-beam computed tomography (CBCT) imaging to examine the C-shaped canal configuration of mandibular and maxillary second molars in an Iraqi subpopulation. The prevalence and configurations of C-shaped canals were evaluated in 368 mandibular second molars and 369 maxillary second molars using CBCT scans. The effects of gender, age, and unilateral/bilateral on the presence of C-shaped canals were investigated. Chi-square and Fisher's exact tests were used to determine the level of significance (p ≤ 0.05), and kappa value was used to check reliability of results of the research. In mandibular second molars, the prevalence of C-shaped canals was 17.4%. The prevalence was significantly higher in females (23%) than males (10.4%) using the chi-square test. There is no significant difference in the prevalence of C-shaped canal depending on age and tooth position. The C2 type was the most common (56.3%). This prevalence did not differ with gender, age, or tooth position. In maxillary second molars, C-shaped canals were present in 7.9%. Type I (subtype C) (fusion of 2 root canals MB-DB) was the most common type of fused root (65.5%). There is no significant difference in the prevalence of C-shaped canal depending on the type of fused root, age, and tooth position. The majority of C-shaped canals in mandibular second molars were bilateral in both genders, but unilateral presence was more common in maxillary second molars in both genders. Within the limits of this study, C-shaped canals were found to be more common in mandibular second molars than in maxillary second molars in an Iraqi subpopulation.


Aging correlation functions of the interrupted fractional Fokker-Planck propagator.
The authors explore aging in a general semi-Markov process with arbitrary waiting time distributions and discuss the role of trapping phenomenon in glasses in determining the waiting time distributions. In certain limits, they obtain a two-time propagator for the fractional Fokker-Planck equation through coordination, but one can generalize the construction to incorporate cutoffs in the aging of the system, i.e., the interrupted aging. The construction allows the incorporation of cutoffs in the aging of the system, and the exploration of signatures of aging effects in systems that eventually achieve equilibrium. Cutoffs in aging effects are illustrated for interrupted fractional diffusion in a harmonic potential and for the on-time probability of a quantum dot system.


Low dose 5-azacytidine is ineffective for remission induction in patients with acute myeloid leukemia.
Low dose 5-azacytidine was administered to 11 patients with acute myeloid leukemia (AML) in hopes of achieving complete remissions by inducing differentiation of leukemic blasts. The patient population included both patients who had received no prior therapy (two patients), as well as patients refractory to primary therapy (five patients) and patients who had relapsed after achieving complete remission (four patients). Both previously untreated patients had a history of myelodysplastic syndrome, and two of the primarily refractory patients had leukemia following chemotherapy for other malignancies. The median age was 55 years (range 36-78 years). Twenty-one courses of 5-azacytidine were administered as 7-day continuous infusions at a dose of 75 mg/m2/day. Significant nonhematologic toxicity was not observed. No patient had a response as defined by bone marrow remission or improvement in transfusion requirement for red blood cells or platelets. Although some patients developed bone marrow hypocellularity (six courses in five patients), none became aplastic, and eight courses in six patients were associated with increased bone marrow cellularity percentage of blasts. Five courses in three patients were inevaluable (one central nervous system hemorrhage, one central nervous system leukemia, three courses in one patient who refused bone marrow aspiration). It is unlikely that low dose 5-azacytidine will be of benefit to patients with AML, and there was no evidence of clinically significant induction of differentiation noted.


A cool head ensures smooth MRI delivery.
Pioneering "state-of-the-art mobile" diagnostic technology, Cobalt claims its mobile MRI service is among the world's most sophisticated charity-run operations of its kind. However, with its fleet of units constantly deployed at, or moving between, hospitals across the South West of England and Wales, the charity faces a potential logistical nightmare. Here, Andy Downton, co-owner and MD of the company's logistics provider, Downton, describes the critical strategic planning and estates expertise fundamental to the success of this "unique service".


Molecular methods for identification and detection of bacterial food pathogens.
The polymerase chain reaction (PCR) shortens conventional microbiological methods for the detection of food pathogens either by replacing the conventional biochemical and serological identification or by its direct use on pre-enrichment media or food products. PCR allows fast and highly reliable identification of bacterial taxa, particularly phenotypically atypical bacterial strains. For reliablity, PCR primers and reaction conditions must be thoroughly optimized and evaluated, appropriate sample preparations must be developed, and a stringent laboratory protocol must be followed. Positive control systems are used to monitor possible inhibition of the reaction and negative controls are needed to monitor for contamination. The most recent developments involve messenger RNA-based (mRNA-based) detection of viable bacterial pathogens and real-time PCR quantitation of pathogens.


Alcohol and aggression: effects of personal threat on human aggression and affective arousal.
Theorists have attempted to account for the relationship between alcohol intoxication and a wide range of aggressive behaviors by ascribing alcohol-related aggression to the disinhibiting effects of alcohol and to its disruptive effects on cognitive processes. Allocation of attention and situational threat have been thought to mediate alcohol-related aggression. In the present study, 72 male social drinkers received either alcohol, a placebo, or a nonalcoholic beverage and were exposed to either threatening or nonthreatening personal information. Measuring levels and duration of aggressive responses on a Taylor-Buss aggression machine, intoxicated subjects were found to be generally more aggressive under threatening than under nonthreatening information conditions. Intoxicated subjects also reported relatively large increases in anger, depression, and tension following the aggression task, which appeared to be affected by the type of information received. These findings concur with and refine previous models suggesting that alcohol focuses the drinker's attention to salient cues in threatening circumstances, thus increasing the likelihood of aggressive behavior.


HIGH LEVELS OF GENETIC VARIABILITY IN THE HAPLOID MOSS PLAGIOMNIUM CILIARE.
Horizontal starch-gel electrophoresis was used to measure variability at 14 enzyme loci from 13 natural populations of the dioecious moss Plagiomnium ciliare. Overall levels of genetic polymorphism were unexpectedly high for a haploid organism. Using a 1% frequency criterion, 71% of the loci surveyed were polymorphic for the species as a whole. The number of alleles per polymorphic locus for the species as a whole was 2.82 ± 0.34 (mean ± standard error), and mean gene diversity per locus was 0.078 ± 0.035. While total gene diversity (HT = 0.178) was similar to that observed for highly outcrossed diploid plants such as pines, the variance within (HS = 0.098 ± 0.027) and among (DST = 0.080 ± 0.033) populations was more evenly distributed than that reported for populations of conifers. Genetic distances between populations ranged from 0.0002 to 0.2064, with mosses from the Piedmont region of the southeastern United States showing less differentiation among populations than did mosses from the Appalachian Mountains. Gene diversity was much reduced in populations from disturbed, secondary forests in the Piedmont (0.058 ± 0.018) relative to those from minimally disturbed, primary forests in the mountains (0.146 ± 0.048). Intensive sampling within populations revealed heterogeneity even within small (5 × 5 cm) clumps. The discovery of high levels of genetic variability in a plant with a dominant haploid life cycle challenges the traditional view of bryophytes as a genetically depauperate group. Multipleniche selection is proposed as a possible explanation for this anomaly, but the data are also consistent with the view that allozyme polymorphisms are selectively neutral.


A haemophilia treatment centre-administered disease management programme in patients with bleeding disorders.
The objective of this study is to describe a disease management programme (DMP) for the bleeding disorder population insured by Indiana's high-risk insurance plan, and to assess the associated costs and outcomes. All bleeding disorder patients, covered by the state plan as their primary health insurance, were enrolled into a DMP administered by the Indiana Hemophilia & Thrombosis Center (IHTC). A pre/post-intervention study design was used, with 1-year pre-enrollment serving as the baseline period and 1-year post-enrollment as the study period. Claims data were used to assess hospitalizations, emergency room (ER) visits, total medical and clotting factor costs and factor units dispensed. Medical records were used to assess disease severity and other comorbidities. Thirty-one continuously enrolled patients had complete data over 2 years. Approximately 84% of the population was male, 81% with haemophilia. The average costs of care in the baseline year and the first year of the programme were $161 441 and $118 293, respectively. The decrease in the total costs was primarily attributed to a decrease in outpatient factor costs, which resulted from decreased factor utilization and lower per unit factor costs. The mean number of inpatient hospital days and ER visits for the DMP population decreased from 1.3 and 1.4 to 0.4 and 0.6, baseline and first year, respectively. Owing to the small sample size and high variability of the population, the differences were not statistically significant. The DMP appears to have reduced the total costs and resource utilization, although the study was underpowered.


Reduction of Candida tropicalis biofilm by photoactivation of a Heterophyllaea pustulata extract.
Biofilm formation is an important problem, since this growth mode confers resistance to drugs usually used in therapeutics. In vitro antifungal activity of extracts obtained from Heterophyllaea pustulata Hook f. (Rubiaceae) were studied against Candida tropicalis biofilms, evaluating the effect of irradiation and the oxidative and nitrosative stresses as possible mechanisms of action. Hexane, benzene, ethyl acetate and ethanol extracts were evaluated at three concentrations (0.2, 0.1 and 0.05 mg/mL) over mature biofilm, under darkness and irradiation. After 48 h of incubation, biofilm quantitation was performed by the O'Toole and Kolter method. Reactive oxygen species (ROS) was measured by nitro-blue tetrazolium (NBT) reaction and reactive nitrogen intermediates (RNI) by the Griess reagent. Superoxide dismutase activation (SOD, NBT assay) and total antioxidant system (FRAP test) were studied. Only the benzene extract at 0.2 mg/mL reduced the biofilms formation. The slight decrease achieved in darkness (17.06 ± 2.80% reduction) was increased by light action (39.31 ± 3.50% reduction), clearly observing a photostimulation. This great reduction was confirmed by confocal microscopy. In darkness, biofilm reduction was mediated by an increase in RNI, whereas under irradiation, the ROS action was most important. Although no SOD activation was observed, a strong stimulation of the total antioxidant system was detected. HPLC analysis established a high content of several anthraquinones in this extract. Biofilm reduction by benzene extract was mainly mediated by oxidative stress triggered under light action, confirming a photodynamic sensitization, which could be attributed to its high content of photosensitizing anthraquinones.


Antibiotic treatment of community acquired pneumonia varies widely across Germany.
Community Acquired Pneumonia (CAP) is a frequent and potentially fatal infectious disease which, in the majority of cases, needs an antibiotic intervention. Aim was to evaluate antibiotic treatment patterns regarding all types of mono- and combination-therapy throughout the local clinical centres (LCCs) represented in the German competence network CAPNETZ (=Community Acquired Pneumonia Network) and to identify clinical indicators for regional differences. We analysed outpatients and inpatients recruited between March 2003 and April 2005. Patient and treatment details were registered online using standardised data entry forms. A logistic regression model was issued for the 4 most frequently applied antibiotics, adjusting for potentially relevant confounders. The study sample consisted of 3221 patients at the age of 18 to 102 years. Overall, aminopenicillins plus betalactamase inhibitor (20.4%), fluoroquinolone (17.0%), macrolides combined with cephalosporins third generation (10.6%) and cephalosporins third generation (8.9%) were most frequently prescribed. After control for potential confounders, significant treatment differences remained between study sites. Regional variability of antibiotic CAP-treatment could not be attributed to a number of clinical or sociodemographic factors. The presented treatment variability ranges within given guidelines, but indicates the need for an ongoing implementation of evidence-based guidelines in order to avoid potential negative clinical or economic consequences.


Analysis of Cervical Sagittal Balance Parameters in MRIs of Patients with Disc-Degenerative Disease.
The aim of this study was to explore the correlations between the different parameters of the cervical sagittal balance in magnetic resonance images (MRI) and evaluate the criteria for their clinical application in disc-degenerative diseases. We conducted a retrospective review of the MRIs of 125 adult outpatients with disc-degenerative diseases of the cervical spine; the images were obtained between May and July 2014 at our institute. The control group comprised 50 volunteers whose MRIs were also obtained. The parameters measured in the MRIs were: neck tilt (NT), T1 slope (T1S), thoracic inlet angle (TIA), and Cobb's angle (C2-7). The correlation between the various parameters was analyzed using the Pearson correlation coefficient. The outpatients group showed moderate correlation between TIA and T1S, a significant correlation between TIA and NT, a weak correlation between T1S and Cobb's angle, and a weakly negative correlation between T1S and NT. Further, the TIA showed no significant difference between the outpatient group and the control group, as per the sample t test. Our findings indicate that TIA, T1S, and NT could be used as indices for the evaluation of cervical sagittal balance and that the TIA could be used as a reference to assess the cervical compensation. Restoration of the NT and T1S should be considered as a goal of surgical treatment during the preoperative planning in patients with disc-degenerative diseases.


The relative entropy is fundamental to adaptive resolution simulations.
Adaptive resolution techniques are powerful methods for the efficient simulation of soft matter systems in which they simultaneously employ atomistic and coarse-grained (CG) force fields. In such simulations, two regions with different resolutions are coupled with each other via a hybrid transition region, and particles change their description on the fly when crossing this boundary. Here we show that the relative entropy, which provides a fundamental basis for many approaches in systematic coarse-graining, is also an effective instrument for the understanding of adaptive resolution simulation methodologies. We demonstrate that the use of coarse-grained potentials which minimize the relative entropy with respect to the atomistic system can help achieve a smoother transition between the different regions within the adaptive setup. Furthermore, we derive a quantitative relation between the width of the hybrid region and the seamlessness of the coupling. Our results do not only shed light on the what and how of adaptive resolution techniques but will also help setting up such simulations in an optimal manner.


Pubertal Stage-Dependent Anthropometric Variations in Turkish Children with Adolescent Idiopathic Scoliosis: An In-Depth Analysis.
BACKGROUND Identifying predictive factors for anthropometric changes during puberty in adolescent idiopathic scoliosis (AIS) is critical for prognosis and management. This study aimed to discern these factors in the Turkish AIS population, by analyzing variations against female breast development stages and male testicular volume, benchmarked against national standards. MATERIAL AND METHODS A cross-sectional study was conducted between 2018 and 2022, involving children aged 10 to 18 years from the Orthopedics and Pediatrics Clinics. AIS patients and controls were assessed concerning pubertal status (Tanner stage), chronological age, skeletal maturation (Tanner-Whitehouse), and anthropometric parameters (height, weight, and body mass index). RESULTS AIS patients were compared to controls, stratified by pubertal stages. In girls across all stages, significant differences emerged in bone age, BMI, and weight between AIS and controls (p<0.01). In boys, AIS patients significantly differed in bone age from controls across all stages (p<0.001). At stage V, controls demonstrated higher BMI than AIS boys (p<0.001), while at stage I, AIS boys had significantly higher height and weight compared to controls (p<0.001). CONCLUSIONS AIS patients demonstrate distinctive pubertal growth abnormalities, with males and females presenting divergent patterns. Understanding these variations could inform better management of AIS during the critical pubertal growth period.


Perfusion scan in pulmonary tumor microembolism: report of a case.
A 76-year-old male patient was admitted to our hospital with the chief complaint of dyspnea. A chest CT scan showed pericardial effusion, mediastinal lymphadenopathy and a tumor in the right ventricle with invasion to the main trunk of the pulmonary artery. A 99mTc MAA perfusion lung scan revealed multiple small subsegmental peripheral defects and a "fissure sign", while the 133Xe ventilation scan was normal. After the chest CT scan and scans of both lungs, tumor microembolism was highly suspected. Open chest surgery was performed. A huge tumor in the right ventricle involving the main trunk of the pulmonary artery was found. In addition, multiple tumor thrombi in the pulmonary arteries and veins were also noted. The pathology was metastatic squamous cell carcinoma. Thereafter, the primary lesion was found by bronchoscopy. The final diagnosis was squamous cell carcinoma of the right lower lobe bronchus with metastases to the right ventricle and pulmonary vessels, and in association with pulmonary tumor microembolism. We present this uncommon case and describe the pulmonary perfusion pattern of the tumor microembolism.