Image scanning difference microscopy.
Here, we propose a novel imaging method, which is called image scanning difference microscopy (ISDM), for superresolution imaging. In ISDM, we implement a detector array composed of 19 avalanche photodiodes (APD) rather than single-point detector in standard confocal microscopy for reconstructing superresolved images with higher signal-to-noise ratio (SNR). Combining with our former proposed fluorescence emission difference (FED) method, we have achieved a lateral resolution of 111 nm (∼λ/6) without the damage of image quality, the highest FED resolution to the best of our knowledge. With its simple setup and remarkable performance, we believe that ISDM can become a versatile observation tool in biology and other fundamental studies. LAY DESCRIPTION: Fluorescence emission difference (FED) microscopy is a really simple and generalisable superresolved fluorescence microscopy method based on PSF engineering and difference algorithm recently. Compared to stimulated-emission-depletion fluorescence microscopy (STED), FED don't need complicated system or precise alignment and polarisation, available for wide variety of dyes and has low photobleaching and phototoxicity for living cells. However, the distortion caused by negative value is one of the biggest obstacles to the further development of FED. In light of this, we propose a novel superresolution imaging method based on the FED method with parallel detection system, which is called image scanning difference microscopy (ISDM). Our method has achieved a significant breakthrough in FED, increasing the resolution further while reducing artefacts generated by negative values, which cannot be accomplished through combining other methods. In addition, ISDM does not require complex setup and optical alignment, long time imaging and imposing no constraint on dyes. Importantly, we realised a transverse resolution of ∼λ/6 (triple diffraction limit) with single wavelength, single incident path and low light intensity, which has never been achieved in any other far-field superresolution microscopy.


Constituents of the essential oil from aerial parts of Chromolaena odorata from Thailand.
The chemical composition of the essential oil from the aerial parts of Chromolaena odorata, collected from Phitsanulok, Thailand was analyzed by means of GC-(FID) and GC-MS. Twenty-two constituents were identified. The major components were pregeijerene (17.6%), germacrene D (11.1%), alpha-pinene (8.4%), beta-caryophyllene (7.3%), vestitenone (6.5%), beta-pinene (5.6%), delta-cadinene (4.9%), geijerene (3.1%), bulnesol (2.9%), and trans-ocimene (2.2%).


Low maternal vitamin D as a risk factor for schizophrenia: a pilot study using banked sera.
Evidence from epidemiology suggests that low maternal vitamin D may be a risk factor for schizophrenia. Based on sera taken during the third trimester, we compared the level of 25 hydroxyvitamin D3 in mothers of individuals with schizophrenia or schizoaffective disorders versus mothers of unaffected controls. For each case, we selected two controls matched on race, gender and date of birth of the offspring. There was no significant difference in third trimester maternal vitamin D in the entire sample (cases = 26, controls = 51). Within the subgroup of black individuals (n = 21), there was a trend level difference in the predicted direction. Maternal vitamin D does not operate as a continuous graded risk factor for schizophrenia, however, the results in the black subgroup raise the possibility that below a certain critical threshold, low levels of maternal vitamin D may be associated with an increased risk of schizophrenia.


Molecular basis and clonal nature of increasing pneumococcal macrolide resistance in South Africa, 2000-2005.
The prevalence and molecular epidemiology of pneumococcal macrolide resistance in South Africa was investigated. Minimum inhibitory concentrations and serotypes of pneumococcal isolates causing invasive disease from 2000-2005 (n=15982), collected through a national laboratory-based surveillance system, were determined. Randomly selected isolates from 2005 (51%; 260/508) had resistance mechanisms determined, and clonality was investigated by pulsed-field gel electrophoresis (PFGE) (n=64) and multilocus sequence typing (n=7). Macrolide resistance increased from 9% (160/1828) in 2000 to 14% (508/3656) in 2005 (P<0.001). Serotype 14 was the most common macrolide-resistant serotype (40%; 760/1921). The majority of macrolide-resistant isolates (75%; 1437/1921) displayed the macrolide-lincosamide-streptogramin B (MLS(B)) phenotype. Of the strains screened genotypically, 57% (147/260) contained erm(B), 27% (71/260) contained mef(A) and 15% (40/260) contained erm(B) and mef(A); 1% (2/260) contained ribosomal mutations. Macrolide-resistant isolates were predominantly penicillin-non-susceptible and multidrug-resistant. Isolates clustered according to serotype by PFGE, and 22% (14/64), 11% (7/64) and 5% (3/64) of isolates were related to the Taiwan(19F)-14, England(14)-9 and Spain(9V)-3 global clones, respectively. Routine use of the 7-valent pneumococcal conjugate vaccine (PCV-7) could reduce the burden of macrolide-resistant pneumococcal disease in South Africa.


Neighborhood disadvantage is associated with sleep disturbance in a sample of trauma-exposed Veterans.
This study examined associations among neighborhood disadvantage, all-night respiratory sinus arrhythmia, fear of sleep, nightmare frequency, and sleep duration in a sample of trauma-exposed Veterans. Participants completed baseline assessments and slept on a mattress actigraphy system for seven nights. Neighborhood disadvantage was assessed with the Area Deprivation Index, a census-based socioeconomic index. Differences between the least and most disadvantaged groups on the sleep variables were analyzed. Data were available from 37 Veterans. Residing in neighborhoods with greater disadvantage was associated with elevated fear of sleep and reduced sleep-period respiratory sinus arrhythmia. No significant differences were observed for nightmare frequency or sleep duration. A regression confirmed that neighborhood context had a significant effect on respiratory sinus arrhythmia, after controlling for other baseline sleep variables. In this sample of Veterans, sleep context may increase hypervigilance in turn serving as a mechanism by which trauma-induced sleep disruptions are maintained.


Pharmacokinetics of recombinant factor VIIa in the rat--a comparison of bio-, immuno- and isotope assays.
Recombinant human factor VIIa (rFVIIa) is an activated coagulation factor for intravenous use as a haemostatic agent in haemophiliacs who generate antibodies against factor VIII or IX. Plasma kinetic studies are important for the understanding of the action of rFVIIa which is exerted in the vascular compartment of the body, more specifically on the vessel walls at the site of injury. In the present study, rats were dosed 100 or 500 micrograms/kg 125I-rFVIIa i.v., without any side effects being observed, and the plasma profile of rFVIIa was studied by 3 different assays that were shown to correlate well at early times post-dose: trichloroacetic acid (TCA)-precipitable drug-related radioactivity, rFVIIa antigen determination by ELISA technique, and the assay of clot activity which is the only clinically applicable assay. The plasma concentration curve could be resolved into 1-3 exponentials, depending on the FVIIa detection principle that was employed. Initially, there was a short (ca. 10 min) phase of increasing concentrations before the attainment of Cmax. This was followed by a plasma recovery (Cmax x plasma volume/dose) in the vicinity of one half of the administered dose. The initial volume of distribution (V1) corresponded to the vascular compartment whereas the volume of distribution at steady state (Vss) was somewhat larger. Whole body clearance (CL-B) of rFVIIa was approx. 1 ml/min per kg, and mean residence time (MRT) and the half-life assumed to be associated with the loss of biological activity was approx. 1 h and 20-45 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


An upper body model for the kinematical analysis of the joint chain of the human arm.
The diagnosis and treatment of many orthopaedic and neurological disorders can benefit from movement analysis of the upper extremities by facilitating an objective and quantitative assessment of the compensatory movement strategies of patients. In this paper, a procedure for upper extremity movement analysis is introduced, which allows the simultaneous measurement of movement in all anatomical axes of the kinematical joint chain of the upper body. In first clinical applications it was shown that the procedure facilitates the detection of pathological movement patterns and therefore, adds significantly to the understanding of upper extremity movement strategies.


Expression and subcellular distribution of rel/NF kappa B transcription factors in the preimplantation mouse embryo: novel kappa B binding activities in the blastocyst stage embryo.
We describe the expression patterns and subcellular localisation of murine rel/NF kappa B transcription factors and their inhibitors during preimplantation development in the mouse. We find that the known rel and I kappa B proteins are ubiquitously expressed during early murine embryogenesis. The differential persistence of individual rel and I kappa B transcripts in the first cleavage stage embryo and analysis of the 3'UTR suggests that rel and I kappa B protein expression may be regulated at the level of mRNA stability and translation. At the stages of early mouse embryogenesis examined, there was no evidence for strong induction of rel dimer translocation into the nucleus. However, novel kappa B-binding proteins are found in the mouse blastocyst and may provide an alternative mechanism for regulation of gene expression via the kappa B motif in the early mouse embryo.


Oxidative damage induced by chlorpyrifos in the hepatic and renal tissue of Kunming mice and the antioxidant role of vitamin E.
Chlorpyrifos is a broad-spectrum, chlorinated organophosphate pesticide employed for pest control in various agricultural and animal husbandries. Acute and chronic exposure to CPF can elicit several adverse effects, including oxidative stress. We investigated neurotoxicity of CPF-treated mice, and evaluated the antioxidant effect of vitamin E against oxidative stress and histological changes in the livers and kidneys of CPF-treated mice. Kunming mice were divided randomly into five exposure groups of six: (A) peanut oil; (B) 3mg/kg CPF; (C) 6 mg/kg CPF; (D) 12 mg/kg CPF; (E) vitamin E (100 mg/kg), 3h after administration of CPF (12 mg/kg) and used as a post-treatment group. Oral administration of high-dose groups (12 mg/kg) CPF led to a significant increase in levels of reactive oxygen species, DNA-protein crosslinks, 8-hydroxy-2-deoxyguanosine and malondialdehyde, decreases in acetylcholinesterase activity and glutathione level, as well as causing hepatic and renal histopathological change. Except for AChE activity levels, administration of vitamin E to CPF-treated mice restored these biochemical parameters to within normal levels, and resulted in overall improvement in damage to livers and kidneys. These data suggest that oxidative stress is involved in CPF-induced toxicity and that vitamin E can protect against the tissue damage induced by CPF.


Is the Presence of a Psychiatric Disorder Associated With More Aggressive Management of Compartment Syndrome?
To determine whether pre-existing psychiatric disorder is associated with potentially unnecessary fasciotomy. Retrospective cohort study. Academic Level-1 trauma center. All the patients with orthopaedic trauma undergoing leg fasciotomy at an academic Level I trauma center from 2006 to 2020. Pre-existing diagnosis of psychiatric disorder. Early primary wound closure and delayed primary wound closure. In total, 116 patients were included. Twenty-seven patients (23%) had a pre-existing diagnosis of psychiatric disorder with 13 having anxiety, 14 depression, 5 bipolar disorder, and 2 ADHD. Several patients had multiple diagnoses. Fifty-one patients (44%) had early primary closure (EPC), and 65 patients (56%) had delayed primary closure. Of patients with a psychiatric disorder, 52% received EPC compared with 42% of patients without a disorder, P = 0.38. This lack of a strong association did not seem to vary across specific psychiatric conditions. After adjusting for sex, age, injury type, and substance abuse, there was still no significant association between a psychiatric disorder and EPC with an odds ratio of 1.08 (95% CI, 0.43-2.75). Among patients with orthopaedic trauma undergoing emergent fasciotomy for acute compartment syndrome, a psychiatric disorder was not associated with a significantly increased rate of possibly unnecessary fasciotomy. Given the potential for a psychiatric condition to complicate the diagnosis of acute compartment syndrome, this data is somewhat reassuring; however, there remains a need for continued vigilance in treating patients with psychiatric conditions and research in this area. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Surveillance or Safekeeping? How School Security Officer and Camera Presence Influence Students' Perceptions of Safety, Equity, and Support.
Target hardening, or increasing the use of security measures, is a frequently used response to perceived safety concerns in schools. Studies are mixed as to their effectiveness on students' perceptions of safety and little is known about their influence on other aspects of school climate, particularly for minority students. This study will examine the association between observed security measures in secondary schools and students' perceptions of safety, equity, and support. School climate surveys were completed by 54,350 students from 98 middle and high schools across the state of Maryland beginning in Spring 2014. Concurrent observations of the school physical environment, including security measures (i.e., officers and cameras), were conducted by trained outside assessors. Multilevel regression analyses examined the association between school security officers and cameras and students' perceptions of safety, equity, and support, while controlling for school and neighborhood characteristics. Cross-level interactions explored differential effects of security measures for Black students. Greater use of security cameras inside the school was related to lower perceptions of safety, equity, and support. A moderate level of security camera use outside the school was related to higher student perceptions of support. Security officer presence was associated with higher perceptions of safety. For black students, cameras were associated with elevated perceptions of safety and support relative to white students. Our findings may suggest that outside cameras and security may be perceived by students as safekeeping, whereas inside cameras may evoke feelings of being viewed as potential perpetrators who need surveillance.


Kinetic profile of the cellular lipid composition in an oleaginous Yarrowia lipolytica capable of producing a cocoa-butter substitute from industrial fats.
Cell growth, lipid accumulation and cellular lipid composition of Yarrowia lipolytica growing on mixtures of industrial fats containing stearic, oleic, linoleic and palmitic acid have been studied. During growth, the strain incorporated oleic and linoleic acids more rapidly than the saturated fatty acids. Relatively high lipid accumulation (up to 0.44 g of lipids per g of dry matter) was observed when stearic acid was included in the culture medium. In contrast, substrates rich in oleic acid did not favor cellular lipid accumulation. The accumulated lipids, mainly composed of triacylglycerols (45-55% w/w), demonstrated a different total fatty acid composition compared with that of the substrate; in all cases, the microorganism showed the unusual capacity to increase its cellular stearic acid level, even if this fatty acid was not found in high concentrations in the substrate. This permitted the synthesis of interesting lipid profiles with high percentages of stearic acid and non-negligible percentages of palmitic and oleic acid, with a composition resembling that of cocoa-butter.


Ukrainian science in the context of its anticolonial struggle.
The current Special Issue entitled "Highlights of Ukrainian Molecular Biosciences" is dedicated to presenting recent contributions in the areas of biochemistry and biophysics, molecular biology and genetics, molecular and cellular physiology, and physical chemistry of biological macromolecules made by researchers either currently working in Ukraine or those who have obtained their training in Ukrainian institutions. Obviously, such a collection can present only a small sample of relevant studies, making the editorial task a particular challenge, as inevitably many deserving research groups were missed. In addition, we are greatly sorrowed that some of the invitees were unable to contribute due to the continued bombardments and military attacks perpetrated by Russia in Ukraine since 2014, and especially in 2022. This Introduction is also intended to provide a broader context for understanding of Ukraine's decolonization struggle, both in science and on the battlefield, and outlines suggestions for the global scientific community.


Intraoperative dermoscopy features of subungual squamous cell carcinoma: a study of 53 cases.
Subungual squamous cell carcinoma (SU-SCC) is the most common malignant tumour of the nail unit. Intraoperative nail dermoscopy has been described only for pigmented tumours, onychomatricoma and glomus tumours. To establish a description of intraoperative dermoscopic features of SU-SCC. A single-centre retrospective cohort of 53 SU-SCC cases over a 5-year period was reviewed by six examiners who individually scored 31 intraoperative dermoscopic features as present or absent. For each feature, the frequency and interobserver agreement was evaluated, then the data were compared and a consensus was reached. No feature had perfect or substantial interobserver agreement. Regarding anatomy and architecture, most tumours involved both the nail bed and nail matrix (n = 34, 64.2%) and had nonparallel lateral side edges (n = 36, 67.9%). Regarding vascular features, several different patterns were found: dotted vessels (n = 49, 92.5%), irregular vessels (n = 47, 88.7%), curved vessels (n = 46, 86.8%), sagittal vessels (n = 45, 84.9%), milky-red areas (n = 42, 79.2%), linear and regular vessels (n = 30, 56.6%), coiled and hairpin vessels (n = 23, 43.4%), and arborizing vessels (n = 16, 30.2%). Pigmented dermoscopy structures included dotted purpura, grey granulation and splinter haemorrhages, which were found in 49 (20.8%), 9 (17%) and 9 (17%) cases, respectively. Other dermoscopic signs were pink background, translucent structureless area, whitish scaly areas, distal plug, yellowish scales and dots, and 'digitiform' proximal edge, which were found in 49 (84.9%), 49 (84.9%), 43 (81.1%), 37 (69.8%), 28 (52.8%) and 22 (41.5%) cases, respectively. Analysis of this first large series of SU-SCC studied by intraoperative dermoscopy suggests that it gives useful information to better approach the diagnosis and to target biopsies.


Silibinin alleviates high glucose-suppressed osteogenic differentiation of human bone marrow stromal cells via antioxidant effect and PI3K/Akt signaling.
High glucose is one of the possible causes for osteoporosis and fracture in diabetes mellitus. Our previous study showed that silibinin can increase osteogenic effect by stimulating osteogenic genes expression in human bone marrow stem cells (hBMSCs). However, no study has yet investigated the effect of silibinin on osteogenic differentiation of hBMSCs cultured with high glucose. The aim of this study was to evaluate the influence of high glucose on osteogenic differentiation of hBMSCs and to determine if silibinin can alleviate those effects. In this study, the hBMSCs were cultured in an osteogenic medium with physiological (normal glucose, NG, 5.5mM) or diabetic (high glucose, HG, 30mM). The effects of silibinin on HG-induced osteogenic differentiation were evaluated by alkaline phosphatas (ALP) activity assay, Von Kossa staining and real time-polymerase chain reaction. HG-induced oxidative damage was also assessed. Western blot were performed to examine the role of PI3K/Akt pathway. We demonstrated that HG suppressed osteogenic differentiation of hBMSCs, manifested by a decrease in expression of osteogenic markers and an increase of oxidative damage markers including reactive oxygen species and lipid peroxide (MDA). Remarkably, all of the observed oxidative damage and osteogenic dysfunction induced by HG were inhibited by silibinin. Furthermore, the PI3K/Akt pathway was activated by silibinin. These results demonstrate that silibinin may attenuate HG-mediated hBMSCs dysfunction through antioxidant effect and modulation of PI3K/Akt pathway, suggesting that silibinin may be a superior drug candidate for the treatment of diabetes related bone diseases.


Photobiomodulation by helium neon and diode lasers in an excisional wound model: A single blinded trial.
Application of different kinds of lasers in clinical and experimental studies causes photobiomodulation that works at localized cellular and humoral level on various biological systems. Increased numbers of fibroblasts, myofibroblast, and degranulation of mast cells have been the observed benefits post-irradiation. Was to find out the effect of irradiation with energy densities of 3.38 J/cm(2), 8 J/cm(2), and 18 J/cm(2) on animal tissue (albino wistar rats) in an excisional wound model and to assess changes in biochemical (hydroxyproline) and histopathological levels in excisional wound model. The animals were divided into 4 groups, which were labeled as L1, diode laser (18 J/cm(2)), L2 Helium-neon (He-Ne, 8 J/cm(2)), L3 diode laser (3.38 J/cm(2)), and sham treatment for control was depicted by C, respectively. Histological and hydroxyproline analysis was performed on 7, 14, 21 days of post-wounding. One-way analysis of variance, ANOVA and Bonferroni's multiple comparison tests were done for tissue hydroxyproline levels. There was no significant increase in the hydroxyproline content (P < 0.005) when observed in study group and compared to controls. Whereas significant epithelizations was seen in group treated with He-Ne laser of intensity of 8 J/cm(2). The experimental observations suggest that low intensity helium-neon laser of 8 J/cm(2) intensity facilitated photo stimulation by tissue repair, but failed to show significant tissue hydroxyproline levels in excisional wound model.


Activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in different stages of colorectal carcinoma.
Reactive oxygen species are involved in the pathogenesis of colorectal carcinoma. Clarification of oxidative/antioxidant specificities of different stages of colorectal carcinoma is of special importance. To determine oxidative/antioxidant status in plasma of patients with different stages of colorectal carcinoma using malondialdehyde concentration, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities and distribution of superoxide dismutase isoforms. Lipid peroxidation and antioxidant enzymes activity were estimated using spectrophotometric methods. Reverse zymography was applied for characterization of superoxide dismutase isoforms. Lipid peroxidation is increased in all groups compared to the control, but without differences between different stages of colorectal carcinoma. Total superoxide dismutase activity is lower in all colorectal carcinoma groups than in control, and there is a significant increase in tumor stage IV when compared with tumor stage II. Manganese superoxide dismutase isoform is dominant in all groups and its relative activities are significantly higher than activities of a copper/zinc isoform. Total peroxidase potential reflected in catalase and glutathione peroxidase activity is increased when compared to the control, but without any significant differences between colorectal carcinoma groups. Glutathione reductase activity is lower in all colorectal carcinoma groups than in control, and a significant decrease in glutathione reductase activity was obtained between patients in tumor stage II and III compared to tumor stage IV. Colorectal carcinoma is characterized by increased oxidative stress and antioxidant disbalance. Progression of disease is followed by an increase in redox disbalance.


Treatment of psoriasis: trioxalen and sunlight.
Eighteen psoriasis patients were treated alternately with 40 mg of trioxalen and sunlight on the right side and sunlight only on the left side. Improvement was apparent faster on the psoralen-exposed side.


The bystander effect-induced formation of micronucleated cells is inhibited by antioxidants, but the parallel induction of apoptosis and loss of viability are not affected.
X-rays induce various DNA damages including strand breaks that lead to formation of micronuclei and chromosomal aberrations as well as increased number of apoptotic cells. Similar effects appear when non-irradiated cells are treated with medium collected from cultures of irradiated cells (irradiation conditioned medium - ICM). This phenomenon was termed "bystander effect". A number of studies suggest that bystander effect appears to be associated with up-regulation of oxidative metabolism. We thus compared the effects of antioxidant Vitamins C and E on the frequency of micronuclei and apoptotic cells in both directly irradiated cell cultures and in cultures exposed to ICM. Addition of Vitamins C or E (1-40 microg/ml) to culture medium after exposure to radiation or ICM reduced the frequency of micronuclei in a concentration-dependent manner. These vitamins had no effect on cell viability, clonogenic survival or the frequency of apoptotic cells under both conditions tested. These results show that the bystander effect causes micronucleation in addition to other known effects and suggest that the factors causing micronucleation by X-irradiation, oxidative DNA damage and incomplete repair, are regulated by apoptosis-independent pathways.


Sister cities and easy passage: HIV, mobility and economies of desire in a Thai/Lao border zone.
It is recognised that people movement can increase potential risk of HIV transmission. In recent years, mobile populations moving across national borders have become a focus for HIV/AIDS prevention campaigns. These programs generally target border "hot zones" that produce high levels of HIV vulnerability due to the degree of mobility and the risk behaviours fostered by these marginal environments. However, high degrees of movement and social exploitation need not be the only criteria for borders to exacerbate HIV vulnerability. The types of social interactions promoted by mobility take many forms. In this paper we consider a border zone between Thailand and Laos to show that the links between movement and HIV vulnerability are not confined to stereotypical instances of coercion and exploitation. Rather we demonstrate that HIV risk in this area is a product of both a sense of community and a sense of difference that together foster a range of interactions based on mobility back and forth across the border. As HIV/AIDS prevention programs increasingly control forms of sexual interaction, the border provides a practical and symbolic opportunity to establish new forms of sexual relationship falling outside these constraints. This tendency to move outside bounds is not limited to border areas but has implications for prevention programs everywhere.


The reliability of P300 and the influence of age, gender and education variables in a 50 years and older normative sample.
The present study aims to investigate the effects of age, gender, and level of education on P300 in a healthy population, aged 50 years and over; and determine the reliability metrics for different conditions and measurement methods. Auditory and visual oddball recordings of 171 healthy adults were investigated. A fully automated preprocessing was applied to elicit ERP P300. Maximum peak amplitude, latency and mean amplitudes were measured. Data were stratified by age, gender, and education to determine group-level differences by using repeat measures of ANOVA. The internal consistency of P300 was calculated by a split-half method using odd-even segments. Test-retest reliability was assessed by calculating the intraclass correlation coefficient (ICC). Maximum peak P300 amplitudes were higher in the 50-64 years age group compared to the >65 years age group; and females showed increased P300 amplitudes compared to males. P300 measures showed fair to good internal consistency and poor to good test-retest reliability. Age and gender should be taken into account when designing ERP studies with elderly individuals. P300 showed good internal consistency in general, between gender groups and age groups. Long-term test-retest reliability was lower but acceptable. These findings can be interpreted as the strength of P300 by being an objective and reliable method independent of cultural differences. Here we underline several factors that may affect P300 measures and discuss other possible factors that should be standardized for P300 to be used in clinical settings.


Developing medicines for the pre-symptomatic stage of degenerative neurological conditions: Challenges and opportunities.
Neurodegenerative disorders have a devastating disease course and an increasing prevalence due to prolonged life expectancy. In the last decades, it has become increasingly clear that these diseases often start much earlier, before the onset of symptoms, creating a potential window for pre-symptomatic treatment, a strategy that is desirable from both the biologic and the ethical point of view. However, studying treatments for a pre-symptomatic population presents objective difficulties. This article intends to give a perspective about opportunities and challenges of pre-symptomatic prevention of neurodegenerative diseases. Besides the requirement for biomarkers that would facilitate both the selection of study population and demonstrating a treatment effect, further considerations about balancing benefits, risks and uncertainties pertaining a pre-symptomatic population will be examined.


Unwinding of the nascent lagging strand by Rep and PriA enables the direct restart of stalled replication forks.
During origin-independent replisome assembly, the replication restart protein PriC prefers to load the replication fork helicase, DnaB, to stalled replication forks where there is a gap in the nascent leading strand. However, this activity can be obstructed if the 5'-end of the nascent lagging strand is near the template branch point. Here we provide biochemical evidence that the helicase activities of Rep and PriA function to unwind the nascent lagging strand DNA at such stalled replication forks. PriC then loads the replicative helicase, DnaB, onto the newly generated, single-stranded template for the purposes of replisome assembly and duplex unwinding ahead of the replication fork. Direct rescue of replication forks by the Rep-PriC and PriA-PriC pathways in this manner may contribute to genomic stability by avoiding the potential dangers of fork breakage inherent to recombination-dependent restart pathways.


Vaccination against Haemonchus contortus: performance of native parasite gut membrane glycoproteins in Merino lambs grazing contaminated pasture.
In a replicated trial, parasitological and antibody responses of grazing weaner Merino sheep were assessed following vaccination with gut membrane proteins prepared from adult worms of the gastrointestinal nematode, Haemonchus contortus. Each vaccinated animal received 100 microg native H11 and 100 microg native H-gal-GP combined together in 5mg Quil A administered intramuscularly on days 0, 34, 80 and 127. Control animals received 5mg Quil A alone on the same days. Vaccinated and unvaccinated control animals grazed pastures contaminated with the parasite from day 34 of the trial, and levels of parasitism were monitored by worm-egg counts (WECs) in faeces and packed cell volumes (PCVs) in blood. The level of larval contamination on pasture was estimated from the worm counts of tracer sheep introduced monthly to the paddocks. WECs and anaemia were significantly reduced in vaccinated animals, and, in contrast to vaccinates, all control sheep required salvage treatment with anthelmintic. By the last 2 months of the trial, pastures grazed by vaccinated animals had significantly lower contamination with H. contortus larvae. Vaccinated animals had high levels of vaccine antigen-specific IgG1 and IgG2 antibodies in plasma, whereas those responses in the control sheep were very low. IgG1 titres in the vaccinated group, but not IgG2 titres, were inversely correlated with worm-egg counts. The levels of systemic IgA and IgE remained low but increased in both groups towards the end of the experiment most probably from exposure to the natural infection from pasture. The results showed that H11 and H-gal-GP behaved like "hidden" antigens producing high levels of protection that were probably mediated through mechanisms involving antibodies, and in particular, IgG1. It was concluded that if similar protective effects could be obtained with recombinant versions of the proteins present in either H11 or H-gal-GP, then the prospects for a commercial Haemonchus vaccine were real.


Physical Education and Sport: Does Participation Relate to Physical Activity Patterns, Observed Fitness, and Personal Attitudes and Beliefs?
The purpose of this study was to examine the associations between physical education (PE) and sports involvement with physical activity (PA), physical fitness, and beliefs about PA among a national sample of adolescents. Data from the National Health and Nutrition Examination Survey National Youth Fitness Survey were used. A total of 459 adolescents aged 12 to 15 years. Adolescents self-reported engagement in the above parameters; muscular fitness objectively determined. Multivariable linear regression. Adolescents who had PE during school days had a higher enjoyment of participating in PE (β = 0.32; P = .01), engaged in more days of being physically active for ≥60 min/d (β = 1.02; P < .001), and performed the plank fitness test longer (β = 17.2; P = .002). Adolescents who played school sports reported that more PA was needed for good health (β = 0.23; P = .04), had a higher enjoyment of participating in PE (β = 0.31; P = .003), engaged in more days of being physically active for ≥60 min/d (β = 0.70; P = .01), performed more pull-ups (β = 2.33; P = .008), had a stronger grip strength (β = 2.5; P = .01), and performed the plank fitness test longer (β = 11.6; P = .04). Adolescents who had PE during school, who had more frequent and long-lasting PE, and who played school sports generally had more accurate perceptions of the amount of PA needed for good health, had greater enjoyment of PE, were more physically active, and performed better on several muscular fitness-related tests. This underscores the importance of PE integration in the schools and encouragement of school sports participation.


High-Uniformity Threshold Switching HfO2-Based Selectors with Patterned Ag Nanodots.
High-performance selector devices are essential for emerging nonvolatile memories to implement high-density memory storage and large-scale neuromorphic computing. Device uniformity is one of the key challenges which limit the practical applications of threshold switching selectors. Here, high-uniformity threshold switching HfO2-based selectors are fabricated by using e-beam lithography to pattern controllable Ag nanodots (NDs) with high order and uniform size in the cross-point region. The selectors exhibit excellent bidirectional threshold switching performance, including low leakage current (<1 pA), high on/off ratio (>108), high endurance (>108 cycles), and fast switching speed (≈75 ns). The patterned Ag NDs in the selector help control the number of Ag atoms diffusing into HfO2 and confine the positions to form reproducible filaments. According to the statistical analysis, the Ag NDs selectors show much smaller cycle-to-cycle and device-to-device variations (C V < 10%) compared to control samples with nonpatterned Ag thin film. Furthermore, when integrating the Ag NDs selector with resistive switching memory in one-selector-one-resistor (1S1R) structure, the reduced selector variation helps significantly reduce the bit error rate in 1S1R crossbar array. The high-uniformity Ag NDs selectors offer great potential in the fabrication of large-scale 1S1R crossbar arrays for future memory and neuromorphic computing applications.


Assessment of contaminated sediments with an indoor freshwater/sediment microcosm assay.
This study was conducted to assess the feasibility of using a 2-L, indoor microcosm assay to evaluate five contaminated sediments (A, B, C, D, and E). Toxic potential was deduced in the light of general contamination of sediments, pollutant partitioning in microcosms, and biological responses of species (Pseudokirchneriella subcapitata, Lemna minor, Daphnia magna, Hyalella azteca, Chironomus riparius): E > A > B > C > D. Sediments mainly were contaminated by metals (lead and zinc). Organic pollutant contents varied among the sediments. The major polycyclic aromatic hydrocarbon (PAH) compounds were pyrene, fluoranthene, and phenanthrene. Sediments A, B, and C highly stimulated duckweed growth (> 700%) and impaired daphnid (< 20%) and amphipod survival (< 30%). Sediment D had no significant effect on pelagic and benthic organisms. Finally, sediment E, the most toxic, limited duckweed growth (inhibition of 82%) and impaired daphnid survival (0% of survival). Amphipods were impaired dramatically by this sediment (0% of survival), in contrast with chironomids, for which no toxic effect was measured. The 2-L, indoor microcosm assay successfully was applied to the assessment of those five contaminated sediments. Sediments A, B, C, and E should not be deposited in gravel quarries, and new, more sensitive endpoint measurements should be developed.


Dimethyl Sulfoxide Inhibits Bile Acid Synthesis in Healthy Mice but Does Not Protect Mice from Bile-Acid-Induced Liver Damage.
Bile acids serve a vital function in lipid digestion and absorption; however, their accumulation can precipitate liver damage. In our study, we probed the effects of dimethyl sulfoxide (DMSO) on bile acid synthesis and the ensuing liver damage in mice induced by bile acids. Our findings indicate that DMSO efficaciously curbs bile acid synthesis by inhibiting key enzymes involved in the biosynthetic pathway, both in cultured primary hepatocytes and in vivo. Contrarily, we observed that DMSO treatment did not confer protection against bile-acid-induced liver damage in two distinct mouse models: one induced by a 0.1% DDC diet, leading to bile duct obstruction, and another induced by a CDA-HFD, resulting in non-alcoholic steatohepatitis (NASH). Histopathological and biochemical analyses unveiled a comparable extent of liver injury and fibrosis levels in DMSO-treated mice, characterized by similar levels of increase in Col1a1 and Acta2 expression and equivalent total liver collagen levels. These results suggest that, while DMSO can promptly inhibit bile acid synthesis in healthy mice, compensatory mechanisms might rapidly override this effect, negating any protective impact against bile-acid-induced liver damage in mice. Through these findings, our study underscores the need to reconsider treating DMSO as a mere inert solvent and prompts further exploration to identify more effective therapeutic strategies for the prevention and treatment of bile-acid-associated liver diseases.


The Sendai virus nonstructural C proteins specifically inhibit viral mRNA synthesis.
An in vitro transcription system for paramyxoviruses is described, in which polymerase-free templates are combined with cell extracts containing polymerase made in vivo via transfected plasmids. Both P and L are required for polymerase activity, and both must be coexpressed for optimum activity. mRNA synthesis here was found to be inversely proportional to the level of C expression, whereas defective interfering genome replication was largely unaffected by the level of C in the extract. The inhibition of transcription appeared to be due to the C' and C, but not the Y1 and Y2 proteins, and only occurred when C'/C was coexpressed with P and L. C'/C appears to intervene during polymerase formation, possibly by forming polymerase complexes which are inactive for transcription, but still competent for genome replication.


Strategies and accomplishments of the Tinnitus Research Consortium.
The Tinnitus Research Consortium (TRC) is sponsored by a philanthropist who wants to accelerate progress in basic and clinical research on tinnitus. The TRC consists of 12 distinguished auditory scientists who began meeting in 1998 twice a year for brainstorming for new research approaches to tinnitus, developing requests for applications, judging the scientific merit of the applications received and reviewing the progress of funded projects. Through these efforts, common confounding variables in tinnitus research have been identified, and solutions to these problems have been suggested. TRC grants have been made up to $100,000.00 per year for three years. The sponsor had provided $600,000.00 per year; so two new grants could be made each year. The good news is that the sponsor's support has been increased by 50% for 2011 so that three grants have been awarded. Some of the landmark studies supported by the TRC over the last 14 years are reviewed as is the changing conceptualization of the pathogenesis of tinnitus and its management. The effect of strategies of the TRC on the applicants, grantees, scientific field, scientific societies and other funding agencies will be discussed. For example, when the TRC was initiated, sessions devoted to tinnitus research at national scientific meetings were rare. Through the efforts of the TRC, the American Tinnitus Association and the American Academy of Audiology, organizations such as the Association for Research in Otolaryngology and the Society for Neuroscience were encouraged to hold special sessions on tinnitus research. Now such organizations have well attended sessions on tinnitus research each year. The size of the TRC grants, large enough to support a substantial research project, has caused several other voluntary agencies to increase the size of their grants toward the TRC standard. The National Institute on Deafness and Other Communication Disorders and other institutes at the National Institutes of Health have devoted far more emphasis on tinnitus. By supporting sound research on tinnitus and recruiting world-class scientists to the field, the TRC has led in making tinnitus research respectable.


Communications systems and their models: Massachusetts parent compliance with recommended specialty care after positive cystic fibrosis newborn screening result.
To evaluate compliance with recommendations for sweat testing/specialty evaluation and genetic counseling after a positive cystic fibrosis newborn screening (CF NBS) result. All infants with positive CF NBS results require a diagnostic sweat test at a CF center. Results that were "screen positive and diagnosis negative" prompted family genetic counseling. Parent compliance with follow-up protocol recommendations was retrospectively analyzed relative to the communications model in place at a particular CF Center. At each of the 5 MA CF centers, 95% of the CF NBS-positive infants completed recommended sweat testing. In contrast, there was wide disparity in compliance (32%-90%) with completion of genetic counseling between CF centers. CF centers that escorted parents through the 2 recommended follow-up steps in 1 day had higher compliance with the second step (genetic counseling) than centers that required a return visit for genetic counseling.


Glucose, but not fat, phase shifts the feeding-entrained circadian clock.
To study the ability of single macronutrients to entrain or phase shift the feeding entrainable circadian oscillator, rats with lesions of the suprachiasmatic nucleus were first maintained on a single daily meal of lab chow until robust anticipatory approaches to the feeder or anticipatory wheel running was established. The meal time was then delayed by 8 h and chow was replaced with a 25-mL solution of 0.2% saccharin or 25 mL of saccharin plus 15 g of glucose. For other phase shifts, rats received either 6 mL of vegetable oil or mineral oil for 2 consecutive days. Consumption of about 6 g (24 kcal) or more of glucose resulted in robust delaying transients on the days after ingestion, whereas saccharin induced only small delays consistent with the initiation of a free-running rhythm with a period greater than 24 h. Surprisingly, consumption of 5.5 g of vegetable oil (47 kcal) did not result in delays greater than those in rats receiving mineral oil. The introduction of oil also produced a severe reduction in approaches to the feeder which could be alleviated by placing inaccessible chow in the feeders between oil meals. Phase shifts with oil were repeated with rats housed in wheels using anticipatory wheel running as a phase marker to assess whether the lack of phase shifts with fat was apparatus dependent. As was the case with approach behavior, anticipatory wheel running was not significantly delayed by vegetable oil consumption. These results indicate that a simple monosaccharide, glucose, has zeitgeber properties for the feeding entrainable oscillator. Vegetable oil, despite a higher caloric content, may be ineffective because of slower gastric emptying and nutrient absorption or because fat is not a good zeitgeber for the feeding entrained circadian oscillator.


Cloning and characterization of canine SHARP1 and its evaluation as a positional candidate for canine early retinal degeneration (erd).
Canine early retinal degeneration (erd) is an early onset form of canine progressive retinal atrophy phenotypically similar to human retinitis pigmentosa. In a previous study, the locus responsible for erd was mapped to canine chromosome 27 in the region corresponding to HSA12p, a region where no human retinal degeneration loci have been mapped. Canine SHARP1 gene has been localized on CFA27 in the erd interval by RH mapping, and considered as a positional candidate gene for erd. SHARP1 was cloned and sequenced from normal and erd affected dogs, and no disease-causing mutations were identified. Genotyping of 117 dogs from informative pedigrees did not reveal any recombinants between SHARP1 and erd. To date SHARP1 gene is the closest gene-specific marker to erd; genotyping additional informative pedigrees, and sequencing SHARP1 upstream regions from normal and affected dogs will be necessary to establish if SHARP1 is involved in this canine retinal disease.


Behavior and weight correlates of weight-control efforts in Australian women living in disadvantage: The READI study.
With increasing obesity rates worldwide, more and more people are actively attempting to lose weight or avoid weight gain, but relatively little is known about what specific behaviors comprise these efforts and which, if any, are associated with better weight control over time. This paper reports relationships between body weight, weight-control efforts and related behaviors over a three-year period in 1,634 Australian women. The women were purposefully recruited from 80 disadvantaged neighborhoods in Victoria, Australia. Weight loss efforts were categorized as trying to lose weight, trying to prevent weight gain and no weight-control efforts. Behavioral correlates examined included different kinds of physical activity and consumption of a number of specific foods types. Self-reported body weight at baseline was higher in women trying to lose weight. Frequency of consumption of low energy density foods was positively associated with reported weight-control efforts, as was frequency of reported total and leisure-time physical activity. Longitudinal associations between changes in weight-control efforts and changes in behaviors were consistent with the cross-sectional findings. At three-year follow up, however, weight-control efforts were not associated with change in body weight. More detailed analyses of specific food choices suggested that part of the explanation of no effect of reported weight-control efforts and weight over time might be that people are not as well-informed as they should be about the energy density of some common foods. In particular, those reporting engagement in weight-control efforts reported reducing consumption of carbohydrate-containing foods such as bread and potatoes more than is justified by their energy content, while they reported increasing consumption of some high energy density foods (e.g., cheese and nuts). It is tentatively concluded that women living in disadvantaged neighborhoods understand messages about weight-control (more activity and foods with lower fat and lower energy density) but that some foods eaten more by women engaged in weight control may reduce the effectiveness of these efforts.


Vitellogenin genes in fish: differential expression on exposure to estradiol.
Three types of vitellogenins (Vgs) namely vitellogenin A (VgA), vitellogenin B (VgB) and vitellogenin C (VgC) have been identified in fishes. The existence of VgA and VgB is reported in the Indian freshwater murrel Channa punctatus. Gene-specific primers were designed using available nucleotide sequences in National Centre for Biotechnology Information (NCBI), for amplification of VgA and VgB cDNA. Differential processing of Vgs is evident in many fishes. Adult male murrel expressed both the VgA and VgB genes when estradiol-17β (E(2)) is injected in vivo and Vg levels in blood quantified by Enzyme linked immunosorbent assay (ELISA) showed a dose-related response in such treatments. Cultured hepatocytes on treatment with E(2), however, expressed only VgB as detected by RT-PCR, suggesting different regulatory mechanism for the VgA and VgB genes.


Lower midbrain dopamine transporter availability in depressed patients: Report from high-resolution PET imaging.
A reduced presynaptic dopamine neurotransmission has long been implicated in major depressive disorder (MDD). However, molecular imaging studies that assessed the dopamine transporter (DAT) availability have led to inconsistent results, partly due to methodological considerations, and to exclusive focus on the striatum, precluding findings in extra-striatal regions. Herein, we leveraged our database of high-resolution Positron Emission Tomography (PET) images acquired with a highly selective radiotracer, [11C]PE2I, to assess striatal and extra-striatal DAT availability in eight patients treated for depression compared to twenty-four healthy controls. Statistical parametric mapping and voxel-based analyses of PET images detected a significant lower DAT availability in depressed patients within the superior part of the midbrain (right, pFWE = 0.002; left, pFWE = 0.006), a region including the ventral tegmental area and the substantia nigra from where the mesocorticolimbic and nigrostriatal dopamine pathways originate. A similar difference was found in the right dorsal putamen (pFWE = 0.012). The statistical power was limited to detect only large effects, due to the size of the patients' sample. The findings support the hypothesis that a reduced presynaptic dopamine function plays a role in the pathophysiology of depression, and that extra-striatal dopamine function should be further investigated.


Further analysis of the replication bypass model for sister chromatid exchange.
The replication bypass model for sister chromatid exchange (SCE) proposed by Shafer is examined in detail. When applied through two cell cycles, the model predicts that potentially observable SCEs induced during one S phase will then be cancelled and rendered undetectable during the subsequent S phase. This aspect of replication bypass is inconsistent with the observation of twin SCEs in tetraploid cells. Furthermore, the model cannot account for the efficient induction of SCEs by non-cross-linking chemical agents.


The crystal structure of Escherichia coli CsdE.
Sulfur incorporations both in the biosynthesis of sulfur-containing cofactors and in the sulfur-modifications of certain tRNAs are all mediated by the sulfur initially delivered from the cysteine desulfurases. Sulfur generated as persulfide from cysteine is transferred to the sulfur acceptor protein to further allow delivery to the required steps within an enzymatic process. CsdA which is one of the three cysteine desulfurases identified in Escherichia coli transfers sulfur to the non Fe-S sulfur-acceptor CsdE, however, the consequence of CsdE accepted sulfur is mostly unknown. In this study, we report the 2.4Å structure of free CsdE determined using X-ray crystallography, and compare the structure with the CsdE structure determined using NMR and also CsdE within the crystal CsdA-CsdE complex. Further analysis suggests that the positive electrostatic potential surfaces of CsdE may mediate interaction with a yet unidentified protein or possibly tRNA to deliver sulfur.


Video clip transfer of radiological images using a mobile telephone in emergency neurosurgical consultations (3G Multi-Media Messaging Service).
The purpose of this study was to validate and assess the accuracy and usefulness of sending short video clips in 3gp file format of an entire scan series of patients, using mobile telephones running on 3G-MMS technology, to enable consultation between junior doctors in a neurosurgical unit and the consultants on-call after office hours. A total of 56 consecutive patients with acute neurosurgical problems requiring urgent after-hours consultation during a 6-month period, prospectively had their images recorded and transmitted using the above method. The response to the diagnosis and the management plan by two neurosurgeons (who were not on site) based on the images viewed on a mobile telephone were reviewed by an independent observer and scored. In addition to this, a radiologist reviewed the original images directly on the hospital's Patients Archiving and Communication System (PACS) and this was compared with the neurosurgeons' response. Both neurosurgeons involved in this study were in complete agreement with their diagnosis. The radiologist disagreed with the diagnosis in only one patient, giving a kappa coefficient of 0.88, indicating an almost perfect agreement. The use of mobile telephones to transmit MPEG video clips of radiological images is very advantageous for carrying out emergency consultations in neurosurgery. The images accurately reflect the pathology in question, thereby reducing the incidence of medical errors from incorrect diagnosis, which otherwise may just depend on a verbal description.


Gene I products of cauliflower mosaic virus detected in extracts of infected tissue.
The product of cauliflower mosaic virus (CaMV) gene I has been characterized from extracts of infected plants. Two size classes of this protein can be identified by the use of specific antiserum. The antiserum was induced against a chimeric protein produced in E. coli from a gene fusion between a fragment of the CaMV genome and the beta-galactosidase gene. A 36-kDa form of the gene I product is associated with virus particles. A 45-kDa form of this product was found only in the insoluble fraction of tissue homogenates. This insoluble fraction, the only fraction found to contain the product of viral gene VI, contains the virally induced inclusion bodies.


Immune properties of mesenchymal stem cells.
Mesenchymal stem cells (MSCs) are multipotent progenitor cells isolated by various relatively easily accessible tissues, such as bone marrow and cord blood. MSCs gained attention because of their ease for in vitro expansion together with their multilineage potential. More recently, in vitro and in vivo immunosuppressive properties have been ascribed to them, as they are able to modulate the function of all major immune cell populations, thus impeding immune responses. The underlying mechanisms of their differentiation and function are not thoroughly understood, but still they represent important candidates for tissue regeneration and manipulation of the immune response in graft rejection, graft versus host disease, and autoimmune disorders. Characteristics and immunogenic profile of MSCs, their interface with immune system and their potential use as immunosuppressive elements in cellular therapeutic protocols are reviewed in this chapter.


Putrescine modulation of depolarization-induced [3H]serotonin release from fish brain synaptosomes.
In this study, we investigated the effects of putrescine, a precursor of polyamine metabolism, on depolarization (potassium chloride, KCl)-induced [3H]serotonin (5-hydroxytryptamine (5-HT)) release from brain synaptosomes of rainbow trout (Oncorhynchus mykiss). An irreversible inhibitor of polyamine metabolism, difluoromethyl-ornithine (DFMO), inhibited the KCl-induced [3H]serotonin efflux, and addition of putrescine (PUT) reversed the inhibitory effects of the former in synaptosomal preparations. In Fura-2/AM loaded synaptosomes, KCl stimulated Ca2+ influx. Hence, prior addition of EGTA abolished the KCl-induced Ca2+ responses, indicating that KCl-induced depolarization recruited Ca2+ from extracellular medium. The DFMO curtailed the KCl-evoked Ca2+ influx, and addition of PUT reversed the inhibitory effects of DFMO. Furthermore, fish brain was found to contain polyamines in high amounts (e.g. putrescine from 600 +/- 20 to 850 +/- 30 nmol/g protein). These results suggest that polyamine putrescine, present in fish brain, might be involved in [3H]serotonin efflux via Ca2+ influx mechanisms.


Storytelling intervention for patients with cancer: part 2--pilot testing.
To evaluate symptom reports and the impact of a nurse-led storytelling intervention in a supportive group setting on mood, stress level, coping with stress, pain, self-efficacy, and satisfaction with life in patients with cancer. Descriptive pilot project using a pretest/post-test control group. Local regional medical center in the Pacific Northwest region of the United States. Convenience sample of 10 patients with various cancer diagnoses; 7 completed the intervention. Participants were randomly assigned to a storytelling or control group. Using a tool kit generated for this project, a nurse facilitator guided storytelling group participants in 12 1.5-hour sessions. Six instruments, symptom assessments, and a retrospective physician chart review were completed for each group. Data were analyzed using repeated measures analysis of variance. Mood, stress, coping, pain, self-efficacy, and satisfaction with life. Comparison of changes in group mean scores revealed a significant decrease in anxiety in the storytelling group despite disease progression. Documentation of psychosocial symptomatology by physicians is limited; however, nursing assessments were useful in determining psychosocial status before and after the intervention. Results can be viewed only in context of a feasibility study and are not generalizable because of a limited sample size. A trained oncology nurse was able to use the storytelling intervention. Initial results are promising and warrant further study. After additional testing, the intervention could be used to enhance storytelling groups for patients with cancer or for individuals who are uncomfortable in or do not have access to storytelling groups.


Dietary prevention of diabetes in the non-obese diabetic mouse.
Diabetes prone NOD female mice were fed diets containing different proteins from just before weaning. Only mice receiving meat meal or casein as the protein source developed diabetes at the rate expected from this colony. Lactalbumin and gluten did not precipitate diabetes except in a small number. Casein hydrolysate in lieu of protein protects against overt diabetes, but only if introduced early. The animals which did not show overt diabetes nevertheless had intermittent trace glycosuria and the majority showed mild degrees of periinsular lymphocytic infiltration.


Experimental and modeling studies of ultrasound-assisted release of phenolics from oak chips into model wine.
The enhancement of release of oak-related compounds from oak chips during wine aging with oak chips may interest the winemaking industry. In this study, the 25-kHz ultrasound waves were used to intensify the mass transfer of phenolics from oak chips into a model wine. The influences of acoustic energy density (6.3-25.8 W/L) and temperature (15-25 °C) on the release kinetics of total phenolics were investigated systematically. The results exhibited that the total phenolic yield released was not affected by acoustic energy density significantly whereas it increased with the increase of temperature during sonication. Furthermore, to describe the mechanism of mass transfer of phenolics in model wine under ultrasonic field, the release kinetics of total phenolics was simulated by both a second-order kinetic model and a diffusion model. The modeling results revealed that the equilibrium concentration of total phenolics in model wine, the initial release rate and effective diffusivity of total phenolics generally increased with acoustic energy density and temperature. In addition, temperature had a negative effect on the second-order release rate constant whereas acoustic energy density had an opposite effect.


Low mortality in necrotizing enterocolitis associated with coagulase-negative Staphylococcus infection.
The aim of this study was to correlate the clinical course of necrotizing enterocolitis (NEC) with infection by coagulase-negative Staphylococcus at the onset of the illness. Records of all newborn infants developing NEC between January 1998 and December 2001 were reviewed. NEC was classified according to the criteria of Bell et al. Numeric variables were described by standard statistical methods. Comparisons between subgroups were performed by parametric statistical tests. Forty-four patients developed NEC stage II (n = 25) or III (n = 19). The incidence was 0.024% of live births in the hospital, and the mortality rate was 9%. The main risk factor was prematurity (84%). Only one-fourth of the patients had gastric residuals. A platelet count of <100,000 cells/mm3 occurred only in grade III NEC. Blood cultures were positive in 34% of the patients. The predominant organism (73%) was coagulase-negative Staphylococcus (CoNS). Neither Clostridium nor Bacteroides species were isolated. Stage II patients were maintained nothing per os (NPO) for 9 +/- 3 days and received antibiotics for 10 +/- 3 days. All of the stage III patients required an operation. In one-third of them, primary peritoneal drainage was initially performed but all required further operative procedures. We report a low incidence and mortality rate of necrotizing enterocolitis. Thrombocytopenia is confirmed as a marker of severity. Positive blood cultures for CoNS may explain, at least in part, the low mortality reported.


Propofol-nitrous oxide versus thiopental-isoflurane-nitrous oxide for general anesthesia.
One hundred and twenty patients undergoing elective operations were randomly assigned to receive anesthesia with either thiopental, 4 mg/kg-isoflurane, 0.2-3%-nitrous oxide, 60-70% (control) or propofol, 2 mg/kg-propofol infusion, 1-20 mg/min-nitrous oxide, 60-70% (propofol). Although anesthetic conditions were similar during the operation, differences were noted in the recovery characteristics. For non-major (superficial) surgical procedures, the times to awakening, responsiveness, orientation, and ambulation were significantly shorter in the propofol group (4 +/- 3, 5 +/- 4, 6 +/- 4, and 104 +/- 36 min) than in the control group (8 +/- 7, 9 +/- 7, 11 +/- 9, and 142 +/- 61 min, respectively). In addition, less nausea and vomiting (20 vs. 45%) and significantly less psychomotor impairment was noted in the non-major propofol (vs. control) group. Following major abdominal operations, recovery characteristics did not differ between propofol and control groups. Delayed emergence (greater than 20 min), significant psychometric impairment, and a high overall incidence of postoperative side effects (55-60%) were noted in both drug treatment groups. The authors conclude that propofol-nitrous oxide compares favorably to thiopental-isoflurane-nitrous oxide for maintenance of anesthesia during short outpatient procedures. However, for major abdominal operations, propofol anesthesia does not appear to offer any clinically significant advantages over a standard inhalational anesthetic technique.


Disrupting metformin adaptation of liver cancer cells by targeting the TOMM34/ATP5B axis.
Metformin, a well-known antidiabetic drug, has been repurposed for cancer treatment; however, recently observed drug resistance and tumor metastasis have questioned its further application. Here, we found that long-term metformin exposure led to metabolic adaptation of hepatocellular carcinoma (HCC) cells, which was characterized by an obvious epithelial-mesenchymal transition (EMT) phenotype and compensatory elevation of oxidative phosphorylation (OXPHOS). TOMM34, a translocase of the outer mitochondrial membrane, was upregulated to promote tumor metastasis in response to metformin-induced metabolic stress. Mechanistically, TOMM34 interacted with ATP5B to preserve F1 FO -ATPase activity, which conferred mitochondrial OXPHOS and ATP production. This metabolic preference for OXPHOS suggested a large requirement of energy supply by cancer cells to survive and spread in response to therapeutic stress. Notably, disturbing the interaction between TOMM34 and ATP5B using Gboxin, a specific OXPHOS inhibitor, increased sensitivity to metformin and suppressed tumor progression both in vitro and in vivo. Overall, this study demonstrates a molecular link of the TOMM34/ATP5B-ATP synthesis axis during metformin adaptation and provides promising therapeutic targets for metformin sensitization in cancer treatment.


The effects of gallamine on field and dorsal root potentials produced by antidromic stimulation of motor fibres in the frog spinal cord.
The effects of gallamine on the intraspinal field potentials and the dorsal root potentials produced by antidromic stimulation of motor fibres were studied in the isolated frog spinal cord preparation. After gallamine (10-(3) M), the duration of the negative field potential produced by antidromic activation of motoneurons (N1 response) was increased often without changing its amplitude. This resulted in an increased passive spread of the antidromic action potential towards the dorsal dendritic regions, where afferent fibres terminate. In the untreated spinal cord, stimulation of motor axons produced a late negative dorsal root potential (VR-DRP) which was depressed after gallamine administration. Abolition of the VR-DRP was frequently associated with the appearance of a short latency, conducted response, in the dorsal roots (EVR-DRP). The earliest component of the EVR-DRP had a latency ranging between 0.5 and 2.5 ms measured after the peak of the N1 response recorded at the motor nucleus. Such a brief latency of the EVR-DRP suggests that this response results from electrical interaction between motoneurons and afferent fibres. After gallamine, the primary afferent depolarization produced by orthodromic stimulation of sensory nerves facilitates the EVR-DRP without necessarily increasing the amplitude or duration of the N1 response. Also, gallamine appears to increase directly the excitability of the afferent fibre terminal arborizations. The nature of the electrical interaction between motoneuron dendrites and afferent fibre terminal arborizations is discussed in terms of two hypotheses: interaction by current flows and by electrical coupling.


Optimization of multiple shoot induction and plant regeneration in Indian barley (Hordeum vulgare) cultivars using mature embryos.
Barley is the fourth most important crop in the world. Development of a regeneration system using immature embryos is both time consuming and laborious. The present study was initiated with a view to develop a regeneration system in six genotypes of Indian barley (Hordeum vulgare) cultivars as a prerequisite to transformation. The mature embryos were excised from seeds and cultured on MS medium supplemented with high and low concentrations of cytokinins and auxins respectively. The MS medium containing 3 mg/L N(6)-benzylaminopurine (BA) and 0.5 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) was found to be the most effective for multiple shoot formation in HOR7231 cultivar that could produce 12 shoots per explant. The other cultivars HOR4409 and HOR3844 produced a minimum number of adventitious shoots (1.33 and 1.67 respectively) on MS medium supplemented with 1 mg/L BA and 0.3 mg/L 2,4-D. The elongated shoots were separated and successfully rooted on MS medium containing 1 mg/L indole-3-acetic acid (IAA). The response of different barley cultivars was found to be varying with respect to multiple shoot production. This is the first report of multiple shoot induction and plantlet regeneration in Indian cultivar of barley which would be useful for genetic transformation.


[Cyclic AMP and control of ion exchanges in the fish intestine].
In isolated intestine of the European Flounder, cyclic AMP and theophylline induce a reduction of the negative transmural potential difference and short circuit current, increase severalfold the passive permeability for chloride and abolish the active transport of this ion. These effects are very different from those described in mammals.


Materno-foetal leptin and insulin-like growth factor in low birth weight neonates.
Low birth weight (LBW) is a health concern in developing countries. Leptin and insulin-like growth factor-I (IGF-I) are factors that influence LBW. A case-control study was conducted at Medani hospital, Sudan. Cases were women who had LBW deliveries ( 2,500 g) and controls were women with normal-weight babies ( 2.500 – 4,000 g). Sociodemographic and obstetrical characteristics were gathered from both groups and leptin and IGF-I levels were measured by ELISA. Cases and controls (45 in each arm) were matched in their basic data. The median (interquartile) of maternal leptin levels [9.9 (1.9 – 21.8) vs. 16.0 (9.6 – 20.8), ng/ml; P0.001] and IGF-I [1.6 (0.7 – 20.0) vs. 6.1 (4.3 – 7.1) ng/ml ; P 0.001] were significantly lower in cases than in controls. Likewise, cord serum leptin [5.8 (2.1 – 12.6) vs. 20.0 (5.1 – 37.8) ng/ml; P0.001] and cord serum IGF-I [1.7 (1.3 – 2.0) vs. 6.9 (5.9 – 7.4) ng/ml; P0.001] levels were significantly lower in cases than in controls. Significant positive correlation was found between birth weight and cord leptin ( r0.398), maternal ( r0.795) and cord ( r0.863) IGF-I levels. Maternal and cord leptin and IGF-I levels were significantly lower in LBW babies.


Geographical distribution and hosts of the cestode Paranoplocephala omphalodes (Hermann, 1783) Lühe, 1910 in Russia and adjacent territories.
Paranoplocephala omphalodes is a widespread parasite of voles. Low morphological variability within the genus Paranoplocephala has led to erroneous identification of P. omphalodes a wide range of definitive hosts. The use of molecular methods in the earlier investigations has confirmed that P. omphalodes parasitizes four vole species in Europe. We studied the distribution of P. omphalodes in Russia and Kazakhstan using molecular tools. The study of 3248 individuals of 20 arvicoline species confirmed a wide distribution of P. omphalodes. Cestodes of this species were found in Microtus arvalis, M. levis, M. agrestis, Arvicola amphibius, and also in Chionomys gud. Analysis of the mitochondrial gene cox1 variability revealed a low haplotype diversity in P. omphalodes in Eurasia.


[On micromorphological changes of bradyzoites of toxoplasma cysts in cerebral tissue after storage under freezing at--20 degrees C (author's transl)].
Toxoplasma bradyzoites in cerebral tissue are no longer infectious and able to replicate after 24 hrs of storage under freezing at--20 degrees C. No intact bradyzoites could micromorphologically be demonstrated in the cysts. Clear changes in the structure and lesions of the cell walls and basic substance of the cysts, and of the bradyzoites are held responsible for the destruction of the parasites being surrounded by host tissue.


Review of microRNA in osteosarcoma and chondrosarcoma.
MicroRNAs (miRNAs) are small noncoding RNAs, which play a complex role in posttranscriptional gene expression and can theoretically be used as a diagnostic or prognostic tool, or therapeutic target for neoplasia. Despite advances in the diagnosis and treatment of skeletal sarcomas, including osteosarcoma and chondrosarcoma, much remains unknown regarding their underpinning molecular mechanisms. Given the recent increasing knowledge base of miRNA roles in neoplasia, both as oncogenes and tumor suppressor genes, this review will focus on the available literature regarding the expression profiles and potential roles of miRNA in skeletal sarcomas. Although this is an emerging field, miRNA profiling may be of use in clarifying competing diagnoses of skeletal sarcomas and possibly indicate patient risk of resistance to traditional chemotherapeutic agents. While detecting and targeting miRNAs is currently limited to experimental investigations, miRNA may be utilized for future clinical management of skeletal sarcomas.


Drug-induced reactive oxygen species (ROS) rely on cell membrane properties to exert anticancer effects.
Pharmacological concentrations of small molecule natural products, such as ascorbic acid, have exhibited distinct cell killing outcomes between cancer and normal cells whereby cancer cells undergo apoptosis or necrosis while normal cells are not adversely affected. Here, we develop a mathematical model for ascorbic acid that can be utilized as a tool to understand the dynamics of reactive oxygen species (ROS) induced cell death. We determine that not only do endogenous antioxidants such as catalase contribute to ROS-induced cell death, but also cell membrane properties play a critical role in the efficacy of ROS as a cytotoxic mechanism against cancer cells vs. normal cells. Using in vitro assays with breast cancer cells, we have confirmed that cell membrane properties are essential for ROS, in the form of hydrogen peroxide (H2O2), to induce cell death. Interestingly, we did not observe any correlation between intracellular H2O2 and cell survival, suggesting that cell death by H2O2 is triggered by interaction with the cell membrane and not necessarily due to intracellular levels of H2O2. These findings provide a putative mechanistic explanation for the efficacy and selectivity of therapies such as ascorbic acid that rely on ROS-induced cell death for their anti-tumor properties.


Human Wharton's jelly mesenchymal stem cells protect neural cells from oxidative stress through paracrine mechanisms.
Mesenchymal stem cells (MSCs) have neuroprotective and immunomodulatory properties, which are partly mediated by extracellular vesicles (EVs) secretion. We aimed to evaluate the effects of human Wharton's jelly-derived MSCs (WJ-MSCs) and their EVs on rat hippocampal cultures subjected to hydrogen peroxide (H2O2). Hippocampal dissociated cultures were either co-cultured with WJ-MSCs or treated with their EVs prior to H2O2 exposure and reactive oxygen species levels and cell viability were evaluated. Coculture with WJ-MSCs or pre-incubation with EVs prior to the insult reduced reactive oxygen species after H2O2 exposure. Cell viability was improved only when coculture was maintained following the insult, while EVs did not significantly improve cell viability. WJ-MSCs have potential antioxidant and neuroprotective effects on hippocampal cultures which might be partially mediated by EVs.


Management of polycythemia vera: A survey of treatment patterns in Italy.
Polycythemia vera (PV) is an acquired clonal hematopoietic stem cell disorder characterized by the overproduction of red blood cells. It has long been underlined that there are differences in treatment patterns in routine practice. Therapeutic strategies have also expanded, and in recent years the JAK1/JAK2 inhibitor ruxolitinib has emerged as a second-line therapeutic option in patients who are intolerant to or resistant to hydroxyurea. Determining the impact of changes on practice patterns is of interest, especially for aspects that lack detailed guidance for management. To gain insights into treatment patterns by clinicians treating patients with PV in Italy, we carried out a survey of 60 hematologists and transfusion specialists. The questions covered: treatment of low-risk patients, definition of significant leukocytosis, splenomegaly and excessive phlebotomies, resistance/intolerance to hydroxyurea, use of ruxolitinib, cytoreductive therapy, and vaccines. In general, the results of the survey indicate that there is a large heterogeneity in management of patients with PV across these areas. While helping to provide greater understanding of treatment patterns for patients with PV in Italy, our survey highlights the need for additional clinical studies to obtain more precise guidance for the routine care of patients with PV.


Electrophysiological effects of diclofurime on rabbit and frog atrial heart muscle.
The effects of diclofurime on the electrical activity of the rabbit sinus node, rabbit atria and frog atrial fibres were studied using microelectrode and the double sucrose gap voltage-clamp techniques respectively. In rabbit sinus node, diclofurime (10(-7) M to 10(-6) M) decreased the action potential (AP) amplitude and maximum rate of depolarization (Vmax), increased the AP duration and slowed the sinus rate. In rabbit atria, the drug reduced the amplitude of the depolarizing phase and Vmax, lengthened the AP duration and decreased the resting membrane potential. In frog atrial fibres, the drug (10(-5) M) depolarized the resting membrane potential, decreased Vmax as well as the plateau amplitude. It inhibited the sodium current (INa) with a dissociation constant of 3.7 X 10(-6) M and a one to one relationship between the drug molecule and the Na channel. Diclofurime did not alter the apparent reversal potential for the fast Na current (ENa) but it inhibited the sodium conductance (GNa) in a frequency-dependent manner. Diclofurime also blocked the slow inward current (Islow) without alteration of Eslow. The block of Islow occurred with a dissociation constant of 2 X 10(-5) M and unity stoichiometry. The data suggest that diclofurime might be effective in the control of cardiac arrythmias since it exhibited both local anaesthetic-like and calcium antagonistic properties.


Molecular and cellular mechanisms of thymosin β4-mediated cardioprotection.
Coronary heart disease is still the leading cause of death in industrialized nations. Reduction of infarct size after acute myocardial infarction and, in addition, improvement of myocardial function and perfusion in acute and chronic myocardial ischemia would enhance cardiac survival. Thymosin β4, a 43-amino acid water-soluble peptide with pleiotropic abilities seems to be a promising candidate for the treatment of ischemic heart disease. During cardiac development, thymosin β4 is essential for vascularization of the myocardium, by targeting all three parts of vessel development, that is, vasculogenesis, angiogenesis, and arteriogenesis. In the adult, thymosin β4 is capable of inducing angiogenesis via activation of survival kinases in an actin-dependent and -independent manner. In addition, thymosin β4 has anti-inflammatory properties by reducing NF-κB p65 activation. These protective effects are further enhanced through increased myocyte and endothelial cell survival accompanied by differentiation of epicardial progenitor cells.


A receptor-like cytoplasmic kinase targeted by a plant pathogen effector is directly phosphorylated by the chitin receptor and mediates rice immunity.
CERK1 is a lysine motif-containing plant pattern recognition receptor for chitin and peptidoglycan. Chitin recognition by OsCERK1 triggers rapid engagement of a rice MAP kinase cascade, which leads to defense response activation. How the MAP kinase cascades are engaged downstream of OsCERK1 remains obscure. Searching for host proteins that interact with Xoo1488, an effector of the rice pathogen Xanthomonas oryzae, we identified the rice receptor-like cytoplasmic kinase, OsRLCK185. Silencing OsRLCK185 suppressed peptidoglycan- and chitin-induced immune responses, including MAP kinase activation and defense-gene expression. In response to chitin, OsRLCK185 associates with, and is directly phosphorylated by, OsCERK1 at the plasma membrane. Xoo1488 inhibits peptidoglycan- and chitin-induced immunity and pathogen resistance. Additionally, OsCERK1-mediated phosphorylation of OsRLCK185 is suppressed by Xoo1488, resulting in the inhibition of chitin-induced MAP kinase activation. These data support a role for OsRLCK185 as an essential immediate downstream signaling partner of OsCERK1 in mediating chitin- and peptidoglycan-induced plant immunity.


Kinetic profile of carbamazepine in an adult Portuguese outpatient population.
The aim of our work was to define the kinetic profile of carbamazepine (CBZ), in order to improve on dosing schedules through a Bayesian approach. Carbamazepine dose/steady-state trough concentrations data pairs and associated information were collected retrospectively on a population of adult epileptic patients. Fifty patients (index population) with two or more available concentrations (total of 174 determinations) met our inclusion criteria. Patients were taking CBZ (200-1800 mg/day) in mono- or polytherapy regimens. The analysis assumed a one-compartmental model with first-order absorption and elimination. Due to the data source (only trough concentrations were measured as part of hospital routine), the volume of distribution was fixed at 1.19 l/kg. The final estimates for CL were: 0.075 +/- 0.027 (mono- and polytherapy), 0.069 +/- 0.020 (monotherapy), and 0.106 +/- 0.037 l/h/kg (polytherapy). In order to validate these results, we assessed their predictive capacity using 18 new patients (validation population), submitted to the same inclusion criteria and using Prediction-Error analysis. The results suggested a different CL value for our population compared to earlier published clearance values. The results also pointed to an increased metabolic rate associated with polytherapy. The prediction capacity of the optimization method derived from a Portuguese population made in an a priori evaluation indicated a low error (-0.04 microg/ml), close to the theoretical zero value. Our results provide specific data on CBZ disposition in a Portuguese population and given the wide variability in the literature values, our data may help improve dosing of CBZ in Portuguese patients.


Mechanisms of Microglia Proliferation in a Rat Model of Facial Nerve Anatomy.
Although microglia exist as a minor glial cell type in the normal state of the brain, they increase in number in response to various disorders and insults. However, it remains unclear whether microglia proliferate in the affected area, and the mechanism of the proliferation has long attracted the attention of researchers. We analyzed microglial mitosis using a facial nerve transection model in which the blood-brain barrier is left unimpaired when the nerves are axotomized. Our results showed that the levels of macrophage colony-stimulating factor (M-CSF), cFms (the receptor for M-CSF), cyclin A/D, and proliferating cell nuclear antigen (PCNA) were increased in microglia in the axotomized facial nucleus (axotFN). In vitro experiments revealed that M-CSF induced cFms, cyclin A/D, and PCNA in microglia, suggesting that microglia proliferate in response to M-CSF in vivo. In addition, M-CSF caused the activation of c-Jun N-terminal kinase (JNK) and p38, and the specific inhibitors of JNK and p38 arrested the microglial mitosis. JNK and p38 were shown to play roles in the induction of cyclins/PCNA and cFms, respectively. cFms was suggested to be induced through a signaling cascade of p38-mitogen- and stress-activated kinase-1 (MSK1)-cAMP-responsive element binding protein (CREB) and/or p38-activating transcription factor 2 (ATF2). Microglia proliferating in the axotFN are anticipated to serve as neuroprotective cells by supplying neurotrophic factors and/or scavenging excite toxins and reactive oxygen radicals.


Genetic influences on ambulatory blood pressure patterns. The Medical College of Virginia Twin Study.
The genetic influence of ambulatory blood pressure and heart rate was examined in 38 pairs of monozygotic twins, 17 pairs of same-sex dizygotic twins, and 11 pairs of opposite-sex dizygotic twins, all aged 15 or 17 years. The data were analyzed taking into consideration that the response was multivariate (24-h values) instead of the usual univariate response. The results demonstrated the heritability of ambulatory blood pressure and heart rate. This was true regardless of whether the estimate of heritability involved monozygotic twin pairs compared to same-sex dizygotic twin pairs only, or all dizygotic twin pairs. The time-related intraclass correlation coefficient within each twin classification indicated that the patterns of response within twin pairs correlated more for monozygotic twin pairs than within twin pairs for either set of dizygotic twin pairs. In addition, although the opposite-sex dizygotic twin pairs may have different mean levels of response, they exhibit a similarity of patterns of response akin to that seen within same-sex dizygotic twin pairs.


Communication deviations in alcoholics; a pilot study.
Impairments in speech, language, voice and hearing were observed in 14 of 15 alcoholics in treatment.


The importance of a pleasant process of treatment: lessons on healing from South India.
This paper considers the significance of the positive and negative aesthetic qualities of different therapies--in other words, how "pleasant" (a term that is elaborated in the paper) it is to undergo various treatments. Interviews were conducted with patients undergoing three forms of healing for mental illness and related problems in the state of Kerala in southern India--ayurvedic (indigenous) psychiatry, allopathic (biomedical) psychiatry, and religious healing. Informants revealed concerns about the aesthetic process of therapy, reporting adverse reactions to allopathic treatments and in some cases asserting that they enjoyed ayurvedic procedures. Some informants with long-term illnesses had chosen to live in the process of therapy and reside indefinitely in the aesthetically engaging environment of a mosque, temple, or church after pursuing medical therapies for years. Thus considerations of the quality of the process of therapy also call for an examination of the limitations of the concept of "cure" for describing what is accomplished in healing in some therapeutic settings.


Investigation of failure mechanisms of nacre at macro and nano scales.
Nacre is a natural composite featuring exceptional mechanical properties such as high strength and high toughness. Its unique structure is now universally applied in engineering bioinspired materials. On the other hand, it is still a technical challenge to investigate its interfacial strength and fracture mechanisms at micro or nano-scale. In this work, the interfacial strength and fracture mechanism of the 'brick-mortar' structure in nacre are investigated using micro-sized cantilever beam and bend samples. As compared to previous works, a high aragonite/biopolymer interfacial strength is observed (~298 MPa). The crack propagation path is investigated via experiment and finite element modelling and compared with the fracture mechanics analysis. It is confirmed that crack deflection to the aragonite/biopolymer interface contributes to a high overall toughness. This work provides a better understanding of the toughening mechanism in nacre and other bioinspired composites.


Corpus callosum in schizophrenia with deficit and non-deficit syndrome: a statistical shape analysis.
The corpus callosum (CC) is the most targeted region in the cerebrum that integrates cognitive data between homologous areas in the right and left hemispheres. Our study used statistical analysis to determine whether there was a correlation between shape changes in the CC in patients with schizophrenia (SZ) (deficit syndrome (DS) and non-deficit syndrome (NDS)) and healthy control (HC) subjects. This study consisted of 27 HC subjects and 50 schizophrenic patients (20 with DS and 30 with NDS). 3 patients with DS and 4 patients with NDS were excluded. Three-dimensional, sagittal, T1-spoiled, gradient-echo imaging was used. Standard anatomical landmarks were selected and marked on each image using specific software. As to comparing the Procrustes mean shapes of the CC, statistically significant differences were observed between HC and SZ (DS+NDS) (p=0.017, James's Fj=73.732), HC and DS (p<0.001, James's Fj=140.843), HC and NDS (p=0.006, James's Fj=89.178) and also DS and NDS (p<0.001, James's Fj=152.967). Shape variability in the form of CC was 0.131, 0.085, 0.082 and 0.086 in the HC, SZ (DS+NDS), DS and NDS groups, respectively. This study reveals callosal shape variations in patients with SZ and their DS and NDS subgroups that take into account the CC's topographic distribution.


Editorial: Energy and Environmental Optics Express-an expanded publication venue for Optics Express.
Editor-in-Chief James Leger announces that the Energy Express section of Optics Express is being expanded to include environmental optics, and introduces its newest Deputy Editor Svetlana Boriskina.


Screening for growth hormone deficiency using urinary growth hormone measurement.
The diagnostic approach in growth hormone deficiency (GHD) is complicated. Two or more provocative tests are essential for definitive diagnosis of GHD. However, such testing cannot be carried out routinely on all subjects with short stature because of the need for hospitalization and blood sampling. A simple screening method for GHD would be of great value. Human growth hormone (hGH) levels were measured in the early morning urine of 192 children aged 7-15 years with height 2.0 s.d. below the mean for their ages. Sixty-eight subjects were selected because they showed a urinary hGH level < 10 ng/g creatinine. They were further examined in terms of bone age and plasma insulin-like growth factor (IGF-I) levels. In 30 subjects, the ratio of bone age: chronological age was < 0.8 and/or plasma IGF-I level was < 0.7 U/mL. Finally 24 of these subjects were examined with provocative tests and other endocrinological tests. Eleven subjects proved to have poor growth hormone secretion and one subject was diagnosed as having Turner syndrome. In conclusion, 11 patients with GHD were diagnosed from 192 children with short stature using urinary hGH measurement as the first screening method. These findings suggests that urinary hGH measurement could be a useful and simple method for detecting GHD.


[Experimental anthrax infection in laboratory animals with differing species susceptibility to the causative agent].
In guinea pigs and noninbred white mice, infected subcutaneously with anthrax which resulted in their death, characteristic generalized infection with the hematogenic contamination of their organs and the signs of intoxication and shock could be observed. In inbred white rats (Fisher 344) the invasion and dissemination of B. anthracis are relatively slightly pronounced, the phenomena of intoxication and shock being clearly prevalent.


Study on the physicochemical properties changes of field aging biochar and its effects on the immobilization mechanism for Cd2+ and Pb2.
It has been widely reported that biochar can be used as a cost-effective amendment to immobilize of heavy metal contaminants in soil. While less research has been conducted on effect of biochar long-term field aging on its properties and the adsorption capability. In this study, the characteristics of aged biochar were investigated by comprehensive characterization to elucidate its mechanism transformation for heavy metal immobilization. Our results showed that, compared to fresh biochar, the relative content of C of aged biochar was reduced by 34.12%, while O was increased by 8.79%. Additionally, the specific surface area, pore volume, pore size and oxygen-containing functional groups of aged biochar were significantly increased compared to the fresh biochar. Batch adsorption experiment indicated that the maximum adsorption for Cd2+ (Qm = 32.157 mg/g) and Pb2+ (Qm = 39.216 mg/g) on aged biochar surface was much larger than that of Cd2+ (Qm = 7.573 mg/g) and Pb2+ (Qm = 8.134 mg/g) on fresh biochar. The underlying adsorption mechanisms for Cd2+ and Pb2+ on fresh biochar were dominated by coprecipitation, cation exchange and cation-π interaction, whereas surface complexation and cation exchange appeared to be more vital for aged biochar, as more active adsorption sites and Oxygen-containing functional groups were formed on its surface during aging, which was well explained by BET, XPS, FTIR and Elemental Analysis. Our study found that the physicochemical properties of biochar changed significantly during field aging. Although these changes increased the adsorption of heavy metals by biochar, the reduced stability of biochar to passivated heavy metal ions.


AMPA receptor subunits expressed by single Purkinje cells.
Several subunits of the glutamate receptor of the AMPA subtype have been cloned recently. These subunits, named GluR1, GluR2, GluR3, and GluR4, exist as two splicing variants (flip and flop). We have determined the subset of AMPA receptor subunits expressed by single cerebellar Purkinje cells in culture. This was achieved by combining whole-cell patch-clamp recordings and a molecular analysis, based on the polymerase chain reaction, of the messenger RNAs harvested into the patch pipette at the end of each recording. We found that each single cell expresses the messenger RNAs encoding the following five subunits: the flip and flop versions of GluR1 and GluR2 as well as GluR3flip, GluR2 being the most abundant. In addition, GluR3flop and GluR4flip were scarcely expressed in half of these neurons, and GluR4flop was never detected.


Hepcidin and inflammation associated with iron deficiency in childhood obesity - A systematic review.
This paper aims to review data on the association of obesity and iron deficiency in children and adolescents, exposing the possible involvement of hepcidin and interleukin-6 (IL-6), obesity's inflammation biomarkers. Articles from PUBMED and WEB OF SCIENCE database with no chronological limit were reviewed to write this systematic review. Keywords such as children, obesity, iron deficiency, and hepcidin were used. After deleting duplicated and review articles, 91 were screened, and 39 were selected as eligible. Sixteen articles were included because they involved serum hepcidin levels in obese children and adolescents as outcomes. Finally, those 16 articles were organized in two tables: one includes therapeutic interventions, and the other does not. As hepcidin was discovered in 2000, the first articles that presented serum hepcidin's quantification in obese children and adolescents, homeostasis iron markers, and their possible association with obesity's inflammatory environment began to be published in 2008. Obesity's chronic inflammation state leads to the production of IL-6, which acts as a signaling molecule for hepcidin synthesis, resulting in iron deficiency, which is common in obese children and adolescents who respond inadequately to iron supplementation. On the other hand, that population responds adequately to therapeutic intervention programs that lead to weight loss, guaranteeing iron homeostasis improvement. Therefore, perhaps it is time to discuss serum hepcidin level quantification as part of evaluating children and adolescents with iron deficiency, which could guide clinical choices that might lead to better therapeutic outcomes.


Absorption of glucose and maltose in congenital glucose-galactose malabsorption.
An intestinal perfusion technique has been used to study absorption of glucose from free glucose and the disacchairde maltose in a patient with congenital glucose-galactose malabsorption. Minimal absorption of glucose occurred from high luminal concentrations of either free glucose (100 mmole/liter) or maltose (50 mmole/liter). Glucose diffused into the intestinal lumen during perfusion of a 2 mmole/liter glucose solution. These observations offer no support for nutritionally important glucose absorption in congenital glucose-galactose malabsorption by either passive diffusion or via a "disaccharidase-related" transport system.


A projection-domain iterative algorithm for metal artifact reduction by minimizing the total-variation norm and the negative-pixel energy.
Metal objects in X-ray computed tomography can cause severe artifacts. The state-of-the-art metal artifact reduction methods are in the sinogram inpainting category and are iterative methods. This paper proposes a projection-domain algorithm to reduce the metal artifacts. In this algorithm, the unknowns are the metal-affected projections, while the objective function is set up in the image domain. The data fidelity term is not utilized in the objective function. The objective function of the proposed algorithm consists of two terms: the total variation of the metal-removed image and the energy of the negative-valued pixels in the image. After the metal-affected projections are modified, the final image is reconstructed via the filtered backprojection algorithm. The feasibility of the proposed algorithm has been verified by real experimental data.