Breaking barriers: a competency-based framework for promoting the integration of the pediatrician's education.
To describe the process of integration and revision of a pediatric program curriculum which resulted in the creation of a competency-based framework recommended in the Brazilian National Curricular Guidelines. Quali-quantitative analysis of an intervention evaluating the students and professors' perception of the pediatric program curriculum (focus groups and semi-structured interviews). Results were discussed during teaching development workshops. A competency-based framework was suggested for the pediatric program from the 3rd to the 6th year. The new curriculum was approved, implemented, and reevaluated six months later. Twelve students (12%) from the 3rd to the 6th year participated in the focus groups, and 11 professors (78.5%) answered the questionnaire. Most participants reported lack of integration among the courses, lack of knowledge about the learning goals of the internships, few opportunities of practice, and predominance of theoretical evaluation. In the training workshops, a competency-based curriculum was created after pediatrics and collective health professors reached an agreement. The new curriculum was focused on general competency, learning goals, opportunities available to learn these goals, and evaluation system. After six months, 93% (104/112) of students and 79% (11/14) of professors reported greater integration of the program and highlighted the inclusion of the clinical performance evaluation. The collective creation of a competency-based curriculum promoted higher satisfaction of students and professors. After being implemented, the new curriculum was considered to integrate the teaching practices and contents, improving the quality of the clinical performance evaluation.


Vibrational spectra of α-glucose, β-glucose, and sucrose: anharmonic calculations and experiment.
The anharmonic vibrational spectra of α-D-glucose, β-D-glucose, and sucrose are computed by the vibrational self-consistent field (VSCF) method, using potential energy surfaces from electronic structure theory, for the lowest energy conformers that correspond to the gas phase and to the crystalline phase, respectively. The results are compared with ultraviolet-infrared (UV-IR) spectra of phenyl β-D-glucopyranoside in a molecular beam, with literature results for sugars in matrices and with new experimental data for the crystalline state. Car-Parrinello dynamics simulations are also used to study temperature effects on the spectra of α-D-glucose and β-D-glucose and to predict their vibrational spectra at 50, 150, and 300 K. The effects of temperature on the spectral features are analyzed and compared with results of the VSCF calculations conducted at 0 K. The main results include: (i) new potential surfaces, constructed from Hartree-Fock, adjusted to fit harmonic frequencies from Møller-Plesset (MP2) calculations, that give very good agreement with gas phase, matrix, and solid state spectra; (ii) computed infrared spectra of the crystalline solid of α-glucose, which are substantially improved by including mimic groups that represent the effect of the solid environment on the sugar; and (iii) identification of a small number of combination-mode transitions, which are predicted to be strong enough for experimental observation. The results are used to assess the role of anharmonic effects in the spectra of the sugars in isolation and in the solid state and to discuss the spectroscopic accuracy of potentials from different electronic structure methods.


[Comparative study of the sensitizing activity of heterologous serum preparations].
Experiments on guinea pigs and adrenalectomized mice showed that the anaphylactogenic properties xenogenic immunoglobulin preparations were 2- to 2.5-fold higher than those of antitoxic sera "Diaferm-3". The partial acid-enzymatic hydrolysis of immunoglobulin preparations obtained by ethanol fractionation permitted a considerable decrease in their sensitizing activity and anticomplementary properties.


Abdominal aortic aneurysm in Behçet's disease: new treatment options for an old and challenging problem.
Arterial involvement in Behçet's syndrome is rare. Aneurysms are common among the arterial lesions, affecting various arteries but mostly the abdominal aorta. Surgical interposition graft insertion is the treatment of choice for large aneurysms. However, vasculitis in these patients is the reason for the notorious surgical complications that result in up to 50% false aneurysms in anastomotic sites. Recently, endovascular repair for abdominal aortic aneurysms has been established. To learn more about vascular Behçet's and, specifically, to compare the results of surgical treatment and endovascular repair of AAA in patients with Behçet's syndrome. We retrieved the medical records of all 53 patients with Behçet's disease admitted to Rambam Medical Center during the years 1985 and 2001, and analysed the results and follow-up of open surgery versus endovascular repair of AAA in patients with known Behçet's syndrome. Of the 53 patients with Behçet's disease 18 had vascular manifestations (34%). AAAs were encountered in 8 patients (15%) and 5 were treated. Open surgery (group 1), under general anesthesia, lasted less than 3 hours with an average aortic damping time of 34 minutes (range 26-41 min) after which the patients were transferred to the intensive care unit for 24-48 hours. Endovascular treatment (group 2), although lasting about the same time without the need for intensive care, necessitated contrast media and fluoroscopy. The length of hospital stay was considerably shorter for patients after endovascular repair compared to open surgery (3 days vs. 6 days). Combined mortality and morbidity was higher in patients who underwent open surgery compared to endovascular repair (one death, one major amputation and three anastomotic pseudoaneurysms compared to one temporary contrast-induced nephropathy). Vasculo-Behçet's patients with AAA are better candidates for endovascular treatment than atherosclerotic patients. Combined morbidity (especially anastomotic pseudoaneurysms) and mortality of Behçet's patients after endovascular repair is considerably lower than after open surgery.


The role of the contact pathway in thrombus propagation.
The continued search for the ideal antithrombotic agent that would prevent or reduce thrombus growth inside blood vessels without an effect on the essential hemostatic functions of blood, including extraluminal thrombin generation and platelet activation, has been going in new directions in the past decade. These directions include studies suggesting that activation of the intrinsic coagulation cascade through contact activation of factor XII, and the resultant thrombin generation is a pathologic event that leads to undesirable consequences. Recent animal studies of contact pathway inhibitors in experimental thrombogenesis suggest that the contact activation pathway of blood coagulation may play a pathogenic role in thrombosis, and pharmacologic inhibition of contact activation may have antithrombotic effects. Development of reasonably potent selective inhibitors of contact activation pathway components or activities now allow for the conduct of studies in various animal species, including primates. These studies have generated interesting data that now support the hypothesis that thrombogenesis in humans may also involve the pathological activation of the intrinsic coagulation cascade. Moreover, baboons, mice, and rabbits, pretreated with antibodies that selectively inhibit factor XII activation, procoagulant factor XIIa activity, or all enzymatic activities of factor XIIa show significantly reduced propensity for occlusive thrombus propagation in various models of acute thrombogenesis on vascular grafts, membrane oxygenators, and even on injured arteries. Since contact activation of blood does not play a demonstrable role in normal hemostasis, and there has been no evidence generated to date suggesting that activation of factor XII has a physiologic function, current research now supports the original concept, developed over 2 decades ago, that temporal pharmacologic inhibition of thrombin generation through the contact pathway may have therapeutic potential and could produce beneficial antithrombotic activities without hemostasis impairment.


Transition metal doped Sb@SnO2 nanoparticles for photochemical and electrochemical oxidation of cysteine.
Transition metal-doped SnO2 nanoparticles (TM-SnO2) were synthesized by applying a thermos-synthesis method, which first involved doping SnO2 with Sb and then with transition metals (TM = Cr, Mn, Fe, or Co) of various concentrations to enhance a catalytic effect of SnO2. The doped particles were then analyzed by using various surface analysis techniques such as transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning transmission X-ray microscopy (STXM), and high-resolution photoemission spectroscopy (HRPES). We evaluated the catalytic effects of these doped particles on the oxidation of L-cysteine (Cys) in aqueous solution by taking electrochemical measurements and on the photocatalytic oxidation of Cys by using HRPES under UV illumination. Through the spectral analysis, we found that the Cr- and Mn-doped SnO2 nanoparticles exhibit enhanced catalytic activities, which according to the various surface analyses were due to the effects of the sizes of the particles and electronegativity differences between the dopant metal and SnO2.


Survival and Success Rates of Monolithic Zirconia Restorations Supported by Teeth and Implants in Bruxer versus Non-Bruxer Patients: A Retrospective Study.
The aim of this study was to assess retrospectively the survival and success rates of monolithic zirconia restorations supported by teeth and implants in bruxer versus non-bruxer patients. Methods: A total of 15 bruxer and 25 non-bruxer patients attended the recall appointment. The bruxer group (mean age of 61.2 ± 13.3 years and follow-up of 58.7 ± 16.8 months) were treated with 331 monolithic zirconia restorations, while the non-bruxer group, with a comparable mean age and follow-up time, were treated with 306 monolithic zirconia restorations. Clinical data were retrieved from the patients' files. At the recall appointment, all supporting teeth and implants were examined for biological and technical complications, and the restorations were evaluated using modified California Dental Association (CDA) criteria. Data were statistically analyzed using survival analysis methods. A significance level of p < 0.05 was used. A total of 31 versus 27 biologic and technical complications were recorded in the bruxer and non-bruxer groups, respectively. No significant differences were found between the two groups regarding overall complications and survival rate. Regarding the type of complication, a significantly higher rate of veneered porcelain chipping (p = 0.045) was observed in the bruxer group. With regard to biological complications, the only complications that exhibited a borderline, although not significant, difference were three fractured teeth exclusively in the bruxer group (p = 0.051), which were replaced with implant-supported restorations. Within the limitations of this study, we conclude that there were no significant differences in the overall survival and success rates of the monolithic zirconia restorations in bruxer versus non-bruxer patients, although veneered zirconia restorations and single tooth abutments exhibited a higher rate of complications in the bruxer group.


Boron-containing capsaicinoids.
This study reports on the preparation of eight new boron-containing capsaicinoids bearing long aliphatic chains, as an expansion of our previous studies to include tertiary amide derivatives into our substrate scope. Our boron-moiety, a pinacolboronate ester (Bpin) fragment, has been incorporated in two locations: as an aryl substituent of the capsaicinoid produced by the reductive amination of veratraldehyde, or at the terminal end of an aliphatic substituent using an iridium catalyzed hydroboration reaction. We report that most compounds in our series show moderate antimicrobial and cytotoxic activity, surpassing activities noted in our previous study.


Maize porridge enriched with a micronutrient powder containing low-dose iron as NaFeEDTA but not amaranth grain flour reduces anemia and iron deficiency in Kenyan preschool children.
Few studies have evaluated the impact of fortification with iron-rich foods such as amaranth grain and multi-micronutrient powder (MNP) containing low doses of highly bioavailable iron to control iron deficiency anemia (IDA) in children. We assessed the efficacy of maize porridge enriched with amaranth grain or MNP to reduce IDA in Kenyan preschool children. In a 16-wk intervention trial, children (n = 279; 12-59 mo) were randomly assigned to: unrefined maize porridge (control; 4.1 mg of iron/meal; phytate:iron molar ratio 5:1); unrefined maize (30%) and amaranth grain (70%) porridge (amaranth group; 23 mg of iron/meal; phytate:iron molar ratio 3:1); or unrefined maize porridge with MNP (MNP group; 6.6 mg iron/meal; phytate:iron molar ratio 2.6:1; 2.5 mg iron as NaFeEDTA). Primary outcomes were anemia and iron status with treatment effects estimated relative to control. At baseline, 38% were anemic and 30% iron deficient. Consumption of MNP reduced the prevalence of anemia [-46% (95% CI: -67, -12)], iron deficiency [-70% (95% CI: -89, -16)], and IDA [-75% (95% CI: -92, -20)]. The soluble transferrin receptor [-10% (95% CI: -16, -4)] concentration was lower, whereas the hemoglobin (Hb) [2.7 g/L (95% CI: 0.4, 5.1)] and plasma ferritin [40% (95% CI: 10, 95)] concentrations increased in the MNP group. There was no significant change in Hb or iron status in the amaranth group. Consumption of maize porridge fortified with low-dose, highly bioavailable iron MNP can reduce the prevalence of IDA in preschool children. In contrast, fortification with amaranth grain did not improve iron status despite a large increase in iron intake, likely due to high ratio of phytic acid:iron in the meal.


Allele frequencies for 40 autosomal SNP loci typed for US population samples using electrospray ionization mass spectrometry.
To type a set of 194 US African American, Caucasian, and Hispanic samples (self-declared ancestry) for 40 autosomal single nucleotide polymorphism (SNP) markers intended for human identification purposes. Genotyping was performed on an automated commercial electrospray ionization time-of-flight mass spectrometer, the PLEX-ID. The 40 SNP markers were amplified in eight unique 5plex PCRs, desalted, and resolved based on amplicon mass. For each of the three US sample groups statistical analyses were performed on the resulting genotypes. The assay was found to be robust and capable of genotyping the 40 SNP markers consuming approximately 4 nanograms of template per sample. The combined random match probabilities for the 40 SNP assay ranged from 10-16 to 10-21. The multiplex PLEX-ID SNP-40 assay is the first fully automated genotyping method capable of typing a panel of 40 forensically relevant autosomal SNP markers on a mass spectrometry platform. The data produced provided the first allele frequencies estimates for these 40 SNPs in a National Institute of Standards and Technology US population sample set. No population bias was detected although one locus deviated from its expected level of heterozygosity.


Efficacy and safety of gemcitabine monotherapy for patients with advanced biliary tract cancer.
The aim of this study was to analyze the efficacy and feasibility of gemcitabine monotherapy in patients with unresectable advanced or recurrent biliary tract cancer (BTC). Six patients with unresectable advanced BTC and 12 patients with recurrent BTC received gemcitabine monotherapy. Gemcitabine (800-1,000 mg/m²) was administered intravenously over 30 minutes on days 1, 8, and 15 every 28 days. Disease and toxicity were assessed once a week in all patients until the completion of gemcitabine treatment. Computed tomographic/magnetic resonance imaging studies were done every 8 weeks during chemotherapy, and every 4 weeks if progressive disease was suspected. Tumor response was determined according to the Response Evaluation Criteria in Solid Tumors. Toxicity was assessed using the National Cancer Institute Common Toxicity Criteria version 2.0. The time to progression and survival time were also calculated. In patients with unresectable BTC, the overall response rate and the median time to progression for patients with partial response or stable disease was 66.7% and 5.68 months, respectively. Clinical benefit was observed in 3 patients with stable disease (50%). The median survival time was 5.2 months. In patients with recurrent BTC, 4 patients (33%) obtained partial responses and 2 patients (17%) had stable disease. The median time to progression was 8.2 months. Six of 12 patients (50%) obtained clinical benefit. The median survival time for cancer of the intrahepatic bile duct, the extrahepatic bile duct, and the ampulla of Vater were 2.8 months, 8.5 months, and 10.7 months, respectively. No significant correlation between the survival time and the resectability of the initial procedure (R number) was detected. The survival time for patients with a performance status of 0 or 1 was significantly longer than that for patients with a performance status of 2 (P=0.0051). Neither grade 3/4 hematologic toxicity nor grade 3/4 nonhematologic toxicity was observed. No treatment-related deaths were observed. Gemcitabine monotherapy may provide a more favorable prognosis in patients with advanced BTC than does best supportive care alone. Moreover, this regimen may represent a therapeutic option for the adjuvant setting in patients with BTC.


The impacts of climate migration on perinatal health and opportunities to safeguard perinatal well-being.
The disparate health consequences of climate change and migration have been separately explored, and the gendered impacts of climate change have been previously established. Nonetheless, there is limited research on the specific nexus of climate change-migration-sexual and reproductive health (SRH). This chapter reviews specific vulnerabilities faced by women and infants throughout the perinatal period, and how these are affected by climate change-induced migration in different migratory contexts. The available literature refers to antenatal and postnatal care utilization, access to water, sanitation, and hygiene facilities, childbirth and delivery challenges, and infant feeding barriers, amongst other concerns. The discussion explored in this chapter highlights the need to develop disaster frameworks that reflect the heterogeneity of outcomes related to specific and unique climate migration contexts.


Dexamethasone and sodium carboxymethyl cellulose prevent postoperative intraperitoneal adhesions in rats.
We aimed to evaluate the effects of the barrier agent sodium carboxymethyl cellulose (SCMC) with and without dexamethasone for the prevention of postoperative adhesion formation in a rat model of postoperative peritoneal adhesion. A total of 160 three-month old male and female Wistar rats underwent a laparotomy, and adhesions were induced by ileocecal abrasion. Rats were randomly assigned to 4 groups (n=40 each): group A, untreated; group B, treated with SCMC only; group C1, treated with SCMC + 3 mg dexamethasone, and group C2, treated with SCMC + 8 mg dexamethasone. After 12 days, adhesion formation and histopathological changes were compared. In groups A, B, C1, and C2, the mortality rates were 10, 5, 5, and 5%, respectively. In groups C1 and C2, the adhesions were filmy and easy to dissect and were milder compared with those in groups A and B. The total adhesion score in group C1 (3.38±0.49) was significantly lower than that of group B (6.01±0.57; P<0.01) or group A (8.01±0.67; P<0.05). There was no significant difference in adhesion formation between groups C1 and C2. Compared with groups A and B, groups C1 and C2 exhibited milder histopathological changes. SCMC in combination with dexamethasone can prevent adhesion formation and is a better barrier agent than SCMC alone. The safety and feasibility of SCMC in combination with dexamethasone to prevent adhesion formation after abdominal surgery warrants further clinical study.


Producer gas engines in villages of less-developed countries.
Producer gas engines could have an important role in the decentralized production of mechanical energy in rural areas of less-developed countries. With this technology mechanical energy is produced from solid fuels by use of internal combustion engines. A comparison with other renewable energy options, on the common basis of energy efficiency and economics, shows that producer gas engines may have significant advantages and deserve serious attention.


Symbiosis of Electrical and Metabolic Oscillations in Pancreatic β-Cells.
Insulin is secreted in a pulsatile pattern, with important physiological ramifications. In pancreatic β-cells, which are the cells that synthesize insulin, insulin exocytosis is elicited by pulses of elevated intracellular Ca2+ initiated by bursts of electrical activity. In parallel with these electrical and Ca2+ oscillations are oscillations in metabolism, and the periods of all of these oscillatory processes are similar. A key question that remains unresolved is whether the electrical oscillations are responsible for the metabolic oscillations via the effects of Ca2+, or whether the metabolic oscillations are responsible for the electrical oscillations due to the effects of ATP on ATP-sensitive ion channels? Mathematical modeling is a useful tool for addressing this and related questions as modeling can aid in the design of well-focused experiments that can test the predictions of particular models and subsequently be used to improve the models in an iterative fashion. In this article, we discuss a recent mathematical model, the Integrated Oscillator Model (IOM), that was the product of many years of development. We use the model to demonstrate that the relationship between calcium and metabolism in beta cells is symbiotic: in some contexts, the electrical oscillations drive the metabolic oscillations, while in other contexts it is the opposite. We provide new insights regarding these results and illustrate that what might at first appear to be contradictory data are actually compatible when viewed holistically with the IOM.


The phase-response effect of size-dependent optical enhancement in a single nanoparticle.
We demonstrate detailed simulations and experiments of near-field phase-response in a single silver nanoparticle. The plasmon-photon interaction is directly observed in the vicinity of silver nanoparticles through a near-field scanning optical microscope (NSOM). Our results manifest the correlation of phase-response and size-dependent optical enhancement. Detailed interference behaviors between optical excitation and plasmon mediated re-radiation are revealed on a single particle basis. This observation facilitates nano-applications in controlling the spatial distribution of surface plasmon (SP) modes by means of nanostructures.


Biochemical and structural characterization of the interaction of memapsin 2 (beta-secretase) cytosolic domain with the VHS domain of GGA proteins.
Memapsin 2 (beta-secretase) is a membrane-associated aspartic protease that initiates the hydrolysis of beta-amyloid precursor protein (APP) leading to the production of amyloid-beta and the onset of Alzheimer's disease (AD). Both memapsin 2 and APP are transported from the cell surface to endosomes where APP hydrolysis takes place. Thus, the intracellular transport mechanism of memapsin 2 is important for understanding the pathogenesis of AD. We have previously shown that the cytosolic domain of memapsin 2 contains an acid-cluster-dileucine (ACDL) motif that binds the VHS domain of GGA proteins (He et al. (2002) FEBS Lett. 524, 183-187). This mechanism is the presumed recognition step for the vesicular packaging of memapsin 2 for its transport to endosomes. The phosphorylation of a serine residue within the ACDL motif has been reported to regulate the recycling of memapsin 2 from early endosomes back to the cell surface. Here, we report a study on the memapsin 2/VHS domain interaction. Using isothermal titration calorimetry, the dissociation constant, K(d), values are 4.0 x 10(-4), 4.1 x 10(-4), and 3.1 x 10(-4) M for VHS domains from GGA1, GGA2, and GGA3, respectively. With the serine residue replaced by phosphoserine, the K(d) decreased about 10-, 4-, and 14-fold for the same three VHS domains. A crystal structure of the complex between memapsin 2 phosphoserine peptide and GGA1 VHS was solved at 2.6 A resolution. The side chain of the phosphoserine group does not interact with the VHS domain but forms an ionic interaction with the side chain of the C-terminal lysine of the ligand peptide. Energy calculation of the binding of native and phosphorylated peptides to VHS domains suggests that this intrapeptide ionic bond in solution may reduce the change in binding entropy and thus increase binding affinity.


Incidence of EDS'76 virus infection in fowl in 1980 in the Netherlands in comparison with the incidence in 1976-1978.
Serological examinations demonstrated that Egg Drop Syndrome 1976 (EDS'76) virus infection was of no significance in the Dutch poultry industry in 1980, in contrast to the situation in 1976-1978 when this infection was of widespread occurrence. The conclusion was reached that the sharp decrease in the incidence of EDS'76 virus infection was due to large scale vaccination in 1978 and 1979. The results of this study show that there is no further need for general EDS'76 vaccinations. However, continuous serological monitoring is necessary to detect flocks for which vaccination is indicated.


Yeast Pab1 interacts with Rna15 and participates in the control of the poly(A) tail length in vitro.
In Saccharomyces cerevisiae, the single poly(A) binding protein, Pab1, is the major ribonucleoprotein associated with the poly(A) tails of mRNAs in both the nucleus and the cytoplasm. We found that Pab1 interacts with Rna15 in two-hybrid assays and in coimmunoprecipitation experiments. Overexpression of PAB1 partially but specifically suppressed the rna15-2 mutation in vivo. RNA15 codes for a component of the cleavage and polyadenylation factor CF I, one of the four factors needed for pre-mRNA 3'-end processing. We show that Pab1 and CF I copurify in anion-exchange chromatography. These data suggest that Pab1 is physically associated with CF I. Extracts from a thermosensitive pab1 mutant and from a wild-type strain immunoneutralized for Pab1 showed normal cleavage activity but a large increase in poly(A) tail length. A normal tail length was restored by adding recombinant Pab1 to the mutant extract. The longer poly(A) tails were not due to an inhibition of exonuclease activities. Pab1 has previously been implicated in the regulation of translation initiation and in cytoplasmic mRNA stability. Our data indicate that Pab1 is also a part of the 3'-end RNA-processing complex and thus participates in the control of the poly(A) tail lengths during the polyadenylation reaction.


A novel truncated variant in SPAST results in spastin accumulation and defects in microtubule dynamics.
Haploinsufficiency is widely accepted as the pathogenic mechanism of hereditary spastic paraplegias type 4 (SPG4). However, there are some cases that cannot be explained by reduced function of the spastin protein encoded by SPAST. The aim of this study was to identify the causative variant of SPG4 in a large Chinese family and explore its pathological mechanism. A five-generation family with 49 members including nine affected (4 males and 5 females) and 40 unaffected individuals in Mongolian nationality was recruited. Whole exome sequencing was employed to investigate the genetic etiology. Western blotting and immunofluorescence were used to analyze the effects of the mutant proteins in vitro. A novel frameshift variant NM_014946.4: c.483_484delinsC (p.Val162Leufs*2) was identified in SPAST from a pedigree with SPG4. The variant segregated with the disease in the family and thus determined as the disease-causing variant. The c.483_484delinsC variant produced two truncated mutants (mutant M1 and M87 isoforms). They accumulated to a higher level and presented increased stability than their wild-type counterparts and may lost the microtubule severing activity. SPAST mutations leading to premature stop codons do not always act through haploinsufficiency. The potential toxicity to the corticospinal tract caused by the intracellular accumulation of truncated spastin should be considered as the pathological mechanism of SPG4.


CMOS-compatible athermal silicon microring resonators.
We propose a new class of resonant silicon optical devices, consisting of a ring resonator coupled to a Mach-Zehnder interferometer, which is passively temperature compensated by tailoring the optical mode confinement in the waveguides. We demonstrate operation of the device over a wide temperature range of 80 degrees. The fundamental principle behind this work can be extended to other photonic devices based on resonators such as modulators, routers, switches and filters.


Long live the worms: methods for maintaining and assessing the viability of intestinal stages of Parascaris spp. in vitro.
In vitro maintenance of helminth parasites enables a variety of molecular, pharmaceutical and immunological analyses. Currently, the nutritional and environmental in vitro requirements of the equine ascarid parasite, Parascaris spp., have not been determined. Additionally, an objective method for assessing viability of Parascaris spp. intestinal stages does not exist. The purpose of this study was to ascertain the in vitro requirements of intestinal stages of Parascaris spp., and to develop a viability assessment method. A total of 1045 worms were maintained in a total of 212 cultures. Worms obtained from naturally infected foals at necropsy were immediately placed in culture flasks containing 200 mL of culture media. A variety of media types, nutrient supplementation and environmental conditions were examined. A motility-based scoring system was used to assess worm viability. Worms maintained in Roswell Park Memorial Institute-1640 had significantly better viability than any other media (P < 0.0001) and all media types supplemented with any of the nutrients examined (P < 0.0001). The use of a platform rocker also significantly improved viability (P = 0.0305). This is the first study to examine the requirements for maintaining Parascaris spp. intestinal stages in vitro and to evaluate their viability based on movement using an objective scoring system.


Liver transplantation for alcoholic hepatitis.
Alcoholic hepatitis (AH) is associated with a high short-term mortality. Currently, most transplant centers require minimum six months of abstinence from alcohol use before considering liver transplant for patients with end stage liver disease. Some recent data are emerging on the benefits and safety of early liver transplantation for patients with severe AH, a population who cannot meet the minimum six months sobriety. This article reviews the current status, benefits, challenges, barriers, and future prospects on early liver transplantation in patients with severe, acute AH.


A unique pharmacophore for activation of the nuclear orphan receptor Nur77 in vivo and in vitro.
Nur77 is a steroid orphan receptor that plays a critical role in regulating proliferation, differentiation, and apoptosis, including acting as a switch for Bcl-2 function. We previously reported that the octaketide cytosporone B (Csn-B) is a natural agonist for Nur77. In this study, we synthesized a series of Csn-B analogues and performed a structure-activity analysis that suggested criteria for the development of a unique pharmacophore to activate Nur77. The components of the pharmacophore necessary for binding Nur77 included the benzene ring, the phenolic hydroxyl group, and the acyl chain of the Csn-B scaffold, whereas the key feature for activating the biological function of Nur77 was the ester group. Csn-B analogues that bound Nur77 tightly not only stimulated its transactivation activity but also initiated mitochondrial apoptosis by means of novel cross-talk between Nur77 and BRE, an antiapoptotic protein regulated at the transcriptional level. Notably, the derivative n-amyl 2-[3,5-dihydroxy-2-(1-nonanoyl)phenyl]acetate exhibited greater antitumor activity in vivo than its parent compounds, highlighting particular interest in this compound. Our findings describe a pathway for rational design of Csn-B-derived Nur77 agonists as a new class of potent and effective antitumor agents.


Breeding Habitat Selection of Reeves's Pheasant (Syrmaticus reevesii) in Dongzhai National Nature Reserve, Henan Province, China.
Reeves's Pheasant (Syrmaticus reevesii) is a threatened pheasant species endemic to China. The habitat use of territorial male birds was surveyed by the help of live decoys in a core area of Dongzhai National Nature Reserve. The breeding habitat selection of this pheasant was examined at two scales (115 m and 250 m scale, i.e. 4.15 hm(2 ) and 19.63 hm(2 ), respectively), including the characteristics at distance scale. Investigation was based on line transect, RS and GIS in Dongzhai National Natural Reserve from 2001 to 2003. Moreover, a range of habitat variables were compared between used and control points at each scale, and stepwise logistic regression was applied to select the key scale and the key habitat factors in relation to breeding habitat selection of this bird. Our results stated that the territorial males at Baiyun occurred mostly in mixed forests, followed by fir forests, pine forests, shrubs, and broadleaf forests. The area of conifer forests was the key factor influencing habitat selection of this bird in breeding period at the scales of 115 m and 250 m, and the proximity of farmland was important for habitat selection in breeding seasons. Furthermore, Reeves's Pheasants attached great importance to the scale of 115 m. When considering a range of habitat variables at all scales within a multivariate regression, the leading factors having effect on habitat selection in the breeding period were areas of conifer forests at 115 m scale and the distance to farmland. In addition, these above results suggested that strengthening the management of suitable habitat, and optimizing the habitat configuration are important in promoting conservation of this bird. However, it also highlighted the importance of initiating future researches on the conifer forests and their impact on the population of Reeves's Pheasants, which would be beneficial to promote the habitat conservation of this pheasant more effectively.


Can telepsychiatry replace in-person psychiatric assessments? A review and meta-analysis of comparison studies.
The authors conducted a review and meta-analysis of the literature comparing telepsychiatry with "in-person" psychiatric assessments. Approximately 380 studies on telepsychiatry published between 1956 and 2002 were identified using MEDLINE, PsycINFO, and cross-referenced bibliographies. Of these, 14 studies with an N > 10 compared telepsychiatry with in-person psychiatry (I-P) using objective assessment instruments or satisfaction instruments. Three of these studies compared high bandwidth (HB) with low bandwidth (LB) telepsychiatry. Fourteen studies of 500 patients met inclusion criteria and were included in the meta-analysis. Telepsychiatry was found to be similar to I-P for the studies using objective assessments. Effect sizes were on average quite small, suggesting no difference between telepsychiatry and I-P. Bandwidth was found to be a significant moderator. Three moderators were tested, effect sizes remained largely heterogeneous, and further analyses are needed to determine the direction of effect. There was no difference between I-P and telepsychiatry between the HB and LB groups, although there are anecdotal data suggesting that HB was slightly superior for assessments requiring detailed observation of subjects. Out of a large telepsychiatry literature published over the past 40+ years, only a handful of studies have attempted to compare telepsychiatry with I-P directly using standardized assessment instruments that permit meaningful comparisons. However, in those studies, the current meta-analysis concludes there is no difference in accuracy or satisfaction between the two modalities. Over the next few years, we expect telepsychiatry to replace I-P in certain research and clinical situations.


17beta-estradiol, genistein, and 4-hydroxytamoxifen induce the proliferation of thyroid cancer cells through the g protein-coupled receptor GPR30.
The higher incidence of thyroid carcinoma (TC) in women during reproductive years compared with men and the increased risk associated with the therapeutic use of estrogens have suggested a pathogenetic role exerted by these steroids in the development of TC. In the present study, we evaluated the potential of 17beta-estradiol (E2), genistein (G), and 4-hydroxyta-moxifen (OHT) to regulate the expression of diverse estrogen target genes and the proliferation of human WRO, FRO, and ARO thyroid carcinoma cells, which were used as a model system. We have ascertained that ARO cells are devoid of estrogen receptors (ERs), whereas both WRO and FRO cells express a single variant of ERalpha that was neither transactivated, modulated, nor translocated into the nucleus upon treatment with ligands. However, E2, G, and OHT were able either to induce the transcriptional activity of c-fos promoter constructs, including those lacking the estrogen-responsive elements, or to increase c-fos, cyclin A, and D1 expression. It is noteworthy that we have demonstrated that the G protein-coupled receptor 30 (GPR30) and the mitogen-activated protein kinase (MAPK) pathway mediate both the up-regulation of c-fos and the growth response to E2, G, and OHT in TC cells studied, because these stimulatory effects were prevented by silencing GPR30 and using the MEK inhibitor 2'-amino-3'-methoxyflavone (PD 98059). Our findings provide new insight into the molecular mechanisms through which estrogens may induce the progression of TC.


Detection of lipid domains in model and cell membranes by fluorescence lifetime imaging microscopy of fluorescent lipid analogues.
The presence of lipid domains in cellular membranes and their characteristic features are still an issue of dividing discussion. Several recent studies implicate lipid domains in plasma membranes of mammalian cells as short lived and in the submicron range. Measuring the fluorescence lifetime of appropriate lipid analogues is a proper approach to detect domains with such properties. Here, the sensitivity of the fluorescence lifetime of1-palmitoyl-2-[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]-hexanoyl]-sn-glycero-3-phospholipid (C6-NBD-phospholipid) analogues has been employed to characterize lipid domains in giant unilamellar vesicles (GUVs) and the plasma membrane of mammalian cells by fluorescence lifetime imaging (FLIM). Fluorescence decay of C6-NBD-phosphatidylcholine is characterized by a short and long lifetime. For GUVs forming microscopically visible lipid domains the longer lifetime in the liquid disordered (ld) and the liquid ordered (lo) phase was clearly distinct, being approximately 7 ns and 11 ns, respectively. Lifetimes were not sensitive to variation of cholesterol concentration of domain-forming GUVs indicating that the lipid composition and physical properties of those lipid domains are well defined entities. Even the existence of submicroscopic domains can be detected by FLIM as demonstrated for GUVs of palmitoyloleoyl phosphatidylcholine/N-palmitoyl-d-sphingomyelin/cholesterol mixtures. A broad distribution of the long lifetime was found for C6-NBD-phosphatidylcholine inserted in the plasma membrane of HepG2 and HeLa cells centered around 11 ns. FLIM studies on lipid domains forming giant vesicles derived from the plasma membrane of HeLa cells may suggest that a variety of submicroscopic lipid domains exists in the plasma membrane of intact cells.


Dietary protein intake and urinary excretion of calcium: a cross-sectional study in a healthy Japanese population.
To evaluate whether habitual excess protein intake is a significant risk factor for calcium loss, we studied the relation between urinary excretion of calcium and protein intakes, in 349 male and 406 female Japanese aged 20-79 y. The subjects were apparently healthy, free-living, and consuming diets of their own choosing. We divided the subjects into two groups: those aged 20-49 y and those aged 50-79 y. In each group, we observed a significant positive correlation between daily urinary excretion of calcium and protein intake. Calcium excretion also correlated positively with daily urinary excretion of urea. Multivariate analyses revealed that in each age group the relation between calcium excretion and urea excretion remained significant even after sex, age, body weight, urinary sodium excretion, and calcium intake were adjusted for. The correlation of calcium excretion with animal protein intake was significantly positive in both sexes and in each age group whereas that with plant protein was not. We observed a significant positive correlation between daily calcium excretion and daily urinary excretion of sulfate. The correlation in 50-79-y old subjects remained significant even after sex, age, body weight, sodium excretion, and calcium intake were adjusted for. Our findings suggest that excess protein, especially that rich in sulfur-containing amino acids, in habitual diets may augment calcium excretion in the urine, at least in the elderly.


A geometric relationship of F2, F3 and F4-statistics with principal component analysis.
Principal component analysis (PCA) and F-statistics sensu Patterson are two of the most widely used population genetic tools to study human genetic variation. Here, I derive explicit connections between the two approaches and show that these two methods are closely related. F-statistics have a simple geometrical interpretation in the context of PCA, and orthogonal projections are a key concept to establish this link. I show that for any pair of populations, any population that is admixed as determined by an F3-statistic will lie inside a circle on a PCA plot. Furthermore, the F4-statistic is closely related to an angle measurement, and will be zero if the differences between pairs of populations intersect at a right angle in PCA space. I illustrate my results on two examples, one of Western Eurasian, and one of global human diversity. In both examples, I find that the first few PCs are sufficient to approximate most F-statistics, and that PCA plots are effective at predicting F-statistics. Thus, while F-statistics are commonly understood in terms of discrete populations, the geometric perspective illustrates that they can be viewed in a framework of populations that vary in a more continuous manner. This article is part of the theme issue 'Celebrating 50 years since Lewontin's apportionment of human diversity'.


Rotational Deformity-When and How to Address Femoral Anteversion and Tibial Torsion.
Rotational deformity is a less common cause of patellar instability than trochlear dysplasia and patella alta. In some cases, rotational deformity is the primary bony factor producing the instability and should be corrected surgically. More research is needed on what are normal values for femoral version and tibial torsion, as well as when the axial plane alignment needs to be corrected. Many tools can be used to evaluate the axial plane and surgeons should be familiar with each of them. Understanding the advantages and disadvantages of each site for osteotomy will help the surgeon choose the most appropriate osteotomy.


Adding Epidemiologically Important Meteorological Data to Peanut Rx, the Risk Assessment Framework for Spotted Wilt of Peanut.
Management of disease affecting peanut in the southeastern United States has benefited from extensive field research identifying disease-associated risk factors since the 1990s. An assessment of risk factors associated with tomato spotted wilt (TSW), caused by tomato spotted wilt virus and spread exclusively by thrips, is available to growers through Peanut Rx, a tool developed to inform peanut management decisions. Peanut Rx provides an assessment of relative TSW risk as an index. The assessment provides information about the relative degree to which a field characterized by a specified suite of practices is at risk of crop loss caused by TSW. Loss results when infection occurs, and infection rates are determined, in part, by factors outside a grower's control, primarily the abundance of dispersing, viruliferous thrips. In this study, we incorporated meteorological variables useful for predicting thrips dispersal, increasing the robustness of the Peanut Rx framework in relation to variation in the weather. We used data from field experiments and a large grower survey to estimate the relationships between weather and TSW risk mediated by thrips vectors, and developed an addition to Peanut Rx that proved informative and easy to implement. The expected temporal occurrence of major thrips flights, as a function of heat and precipitation, was translated into the existing risk-point system of Peanut Rx. Results from the grower survey further demonstrated the validity of Peanut Rx for guiding growers' decisions to minimize risk of TSW.


Functional identification of the glycerol permease activity of Arabidopsis thaliana NLM1 and NLM2 proteins by heterologous expression in Saccharomyces cerevisiae.
NLM proteins (NOD26-like major intrinsic proteins) from plants contain amino acid sequence signatures which can be found in aquaporins including plant plasma membrane intrinsic proteins and tonoplast intrinsic proteins and glycerol permeases such as the Escherichia coli GlpF and the yeast FPS1 proteins. Heterologous expression of two members of the NLM subgroup from Arabidopsis thaliana (AtNLM1 and AtNLM2) in baker's yeast demonstrated the glycerol permease activity in addition to the previously described aquaporin activity of AtNLM1. The transport was non-saturable up to 100 mM extracellular glycerol concentration. Longer-chain sugar alcohols did not compete with the transport of radiolabelled glycerol and hexoses were also not transported through the pore.


Evidence for genetic linkage between a polymorphism in the adenosine 2A receptor and panic disorder.
Data from clinical and behavioral pharmacological studies have implicated adenosine in anxiety behaviors, while genetic studies have suggested that adenosine receptors may be associated with panic disorder. We have undertaken an analysis of several DNA sequence variations in the adenosine 2A receptor (ADORA2A) in a large sample of panic disorder pedigrees. Individuals from 70 panic disorder pedigrees, and 83 child-parent 'trios', were genotyped at five single-nucleotide polymorphisms (SNPs) in and near the ADORA2A gene and were analyzed for genetic linkage and association. Linkage analysis revealed elevated LOD scores for a silent substitution (1083C/T, SNP-4) in the second coding exon. This SNP has been previously reported to be associated with panic disorder. We observed a maximal heterogeneity LOD score of 2.98 (theta=0) under a recessive genetic model and narrow diagnostic model. Other SNPs showed no evidence for linkage. Association tests were not significant for any of the five ADORA2A SNPs. When SNP haplotypes were assessed in the triads with TRANSMIT, one 3-marker haplotype (SNPs 1, 4, 5) was nominally significantly associated with panic disorder (p=0.029). Pairwise estimations of linkage disequilibrium between the SNPs showed strong patterns of linkage disequilibrium across the ADORA2A locus. Analyses carried out by broadening the panic disorder phenotype to include agoraphobia continued to support linkage to ADORA2A. Our findings provide evidence for a susceptibility locus for panic disorder, and possibly including agoraphobia, either within the ADORA2A gene or in a nearby region of chromosome 22, and serves as the first successful candidate gene replication study in panic disorder.


Deletion of smn-1, the Caenorhabditis elegans ortholog of the spinal muscular atrophy gene, results in locomotor dysfunction and reduced lifespan.
Spinal muscular atrophy is the most common genetic cause of infant mortality and is characterized by degeneration of lower motor neurons leading to muscle wasting. The causative gene has been identified as survival motor neuron (SMN). The invertebrate model organism Caenorhabditis elegans contains smn-1, the ortholog of human SMN. Caenorhabditis elegans smn-1 is expressed in various tissues including the nervous system and body wall muscle, and knockdown of smn-1 by RNA interference is embryonic lethal. Here we show that the smn-1(ok355) deletion, which removes most of smn-1 including the translation start site, produces a pleiotropic phenotype including late larval arrest, reduced lifespan, sterility as well as impaired locomotion and pharyngeal activity. Mutant nematodes develop to late larval stages due to maternal contribution of the smn-1 gene product that allows to study SMN-1 functions beyond embryogenesis. Neuronal, but not muscle-directed, expression of smn-1 partially rescues the smn-1(ok355) phenotype. Thus, the deletion mutant smn-1(ok355) provides a useful platform for functional analysis of an invertebrate ortholog of the human SMN protein.


Risk of malignancy in serous cystic neoplasms of the pancreas.
In contrast to mucinous cystic neoplasms of the pancreas, which are known to have considerable malignant potential, the serous variant is generally thought to be benign. There are, however, several reports of malignancy in serous cystic neoplasms of the pancreas. To assess the risk of malignancy of serous cystic tumors of the pancreas and to investigate specific clinical and histological features. Clinical and pathological characteristics of benign and malignant serous cystic neoplasms of the pancreas were investigated by a review of the literature and documented by a case of a serous cystadenocarcinoma and immunohistochemical analysis of a series of serous cystadenomas. Reviewing the literature prevalence, age and sex distribution of serous cystic neoplasms were analyzed. The prevalence of cancer among serous cystic neoplasms reported since 1989 was 3%. Serous cystadenoma of the pancreas present at an earlier age (61 years) than serous cystadenocarcinoma (66 years; p = 0.056) and are symptomatic in the majority of patients. Pathological examination of the primary tumor was not able to distinguish cystadenoma from cystadenocarcinoma in 38% of cases. In 25% the diagnosis of cancer was established only after growth of metachronous metastases. In the present case, nuclear atypia, papillary structures, proliferation marker Ki-67 and p53 protein were increased in the primary tumor and/or metachronous metastasis. Serous cystic neoplasms of the pancreas do have malignant potential with a risk of malignancy of 3% and should be surgically treated if the operative risk is acceptable. Routine analysis of genetic and proliferation markers may improve diagnosis of malignancy in these tumors.


Inhaled whole exhaust and its effect on exercise performance and vascular function.
Internal combustion engines are a major source of particulate matter (PM) which has been shown to result in vasoconstriction, yet no present study to our knowledge has investigated the effect of exhaust emissions on both exercise performance and the vasculature. To examine the effect of freshly generated whole exhaust on exercise performance, pulmonary arterial pressure (PP), and flow-mediated vasodilation (FMD) of the brachial artery. Sixteen male, collegiate athletes (age: 20.8±1.28 years) were randomly assigned to submaximal exercise for 20 min followed by a 6 min maximal work accumulation exercise test in either high PM (HPM) or low PM (LPM) conditions on two consecutive days. After a 7-day washout period, subjects completed identical exercise trials in the alternate condition. HPM conditions were generated from a 4-cycle gasoline engine. The participants' PP and FMD were assessed before and after each exercise trial by tricuspid regurgitant velocity and brachial artery imaging, respectively. Total work (LPM: 108.0±14.8 kJ; HPM: 104.9±15.2 kJ, p=0.019) and FMD (LPM: 8.17±6.41%; HPM: 6.59±2.53%; p=0.034) significantly decreased in HPM while PP was significantly increased (LPM: 16.9±1.13 mmHg; HPM: 17.9±1.70 mmHg; p=0.004). A significant correlation was identified between the change in exercise performance and the change in FMD (r=0.494; p=0.026) after the first HPM trial. Exercise performance declined in HPM conditions in part due to impaired vasodilation in the peripheral vasculature.


Globally convergent autocalibration using interval analysis.
We address the problem of autocalibration of a moving camera with unknown constant intrinsic parameters. Existing autocalibration techniques use numerical optimization algorithms whose convergence to the correct result cannot be guaranteed, in general. To address this problem, we have developed a method where an interval branch-and-bound method is employed for numerical minimization. Thanks to the properties of Interval Analysis this method converges to the global solution with mathematical certainty and arbitrary accuracy and the only input information it requires from the user are a set of point correspondences and a search interval. The cost function is based on the Huang-Faugeras constraint of the essential matrix. A recently proposed interval extension based on Bernstein polynomial forms has been investigated to speed up the search for the solution. Finally, experimental results are presented.


Chemical evidence for the effect of Urochloa ruziziensis on glyphosate-resistant soybeans.
Soybean (Glycine max) is an important oleaginous legume that has been cultivated in new areas in Brazil, including pastures. Problems of reduced production yields have been reported by soybean growers when the crop is sown immediately after desiccation of pastures of Urochloa spp. using glyphosate. The objective of this work was to extract, isolate and identify the major chemicals from U. ruziziensis that have phytotoxic activity and to evaluate the possible relation between this effect and reduced soybean yield. U. ruziziensis plants at the flowering stage were desiccated using glyphosate at 1.44 kg ha-1 . The plants were collected between five and ten days after treatment. Extracts of dried and ground shoots were obtained by sequential extraction with hexane, dichloromethane and methanol. The results of wheat coleoptile bioassays indicated that the methanol extract was more inhibitory than the dichloromethane extract regardless of glyphosate application. Protodioscin, a steroidal saponin, was isolated from the extract as the major component and the activities of this compound were in good agreement with those found for the extract. The release of this compound into the soil is a plausible explanation for the decrease in production observed in transgenic soybean crop after desiccation of U. ruziziensis. © 2017 Society of Chemical Industry.


Impacts of high temperature on adverse birth outcomes in Seoul, Korea: Disparities by individual- and community-level characteristics.
Few studies have examined temperature's effect on adverse birth outcomes and relevant effect modifiers. We investigated associations between heat and adverse birth outcomes and how individual and community characteristics affect these associations for Seoul, Korea, 2004-2012. We applied logistic regression to estimate associations between heat index during pregnancy, 4 weeks before delivery, and 1 week before delivery and risk of preterm birth and term low birth weight. We investigated effect modification by individual (infant's sex, mother's age, and mother's educational level) and community characteristics (socioeconomic status (SES) and percentage of green areas near residence at the gu level, which is similar to borough in Western countries). We also evaluated associations by combinations of individual- and community-level SES. Heat exposure during whole pregnancy was significantly associated with risk of preterm birth. An interquartile (IQR) increase (5.5 °C) in heat index during whole pregnancy was associated with an odds ratio (OR) of 1.033 (95% CI 1.005, 1.061) with NO2 adjustment, and 1.028 (95% CI 0.998, 1.059) with PM10 adjustment, for preterm birth. We also found significant associations with heat exposure during 4 weeks before delivery and 1 week before delivery on preterm birth. We did not observe significant associations with term low birth weight. Higher risk of heat on preterm birth was associated with some individual characteristics such as infants with younger or older mothers and lower community-level SES. For combinations of individual- and community-level SES, the highest and most significant estimated effect was found for infants with low educated mothers living in low SES communities, with suggestions of effects of both individual-and community-level SES. Our findings have implications for evaluating impacts of high temperatures on birth outcomes, estimating health impacts of climate change, and identifying which subpopulations and factors are most relevant for disparities in this association.


Longitudinal dispersion coefficients for numerical modeling of groundwater solute transport in heterogeneous formations.
Most recent research on hydrodynamic dispersion in porous media has focused on whole-domain dispersion while other research is largely on laboratory-scale dispersion. This work focuses on the contribution of a single block in a numerical model to dispersion. Variability of fluid velocity and concentration within a block is not resolved and the combined spreading effect is approximated using resolved quantities and macroscopic parameters. This applies whether the formation is modeled as homogeneous or discretized into homogeneous blocks but the emphasis here being on the latter. The process of dispersion is typically described through the Fickian model, i.e., the dispersive flux is proportional to the gradient of the resolved concentration, commonly with the Scheidegger parameterization, which is a particular way to compute the dispersion coefficients utilizing dispersivity coefficients. Although such parameterization is by far the most commonly used in solute transport applications, its validity has been questioned. Here, our goal is to investigate the effects of heterogeneity and mass transfer limitations on block-scale longitudinal dispersion and to evaluate under which conditions the Scheidegger parameterization is valid. We compute the relaxation time or memory of the system; changes in time with periods larger than the relaxation time are gradually leading to a condition of local equilibrium under which dispersion is Fickian. The method we use requires the solution of a steady-state advection-dispersion equation, and thus is computationally efficient, and applicable to any heterogeneous hydraulic conductivity K field without requiring statistical or structural assumptions. The method was validated by comparing with other approaches such as the moment analysis and the first order perturbation method. We investigate the impact of heterogeneity, both in degree and structure, on the longitudinal dispersion coefficient and then discuss the role of local dispersion and mass transfer limitations, i.e., the exchange of mass between the permeable matrix and the low permeability inclusions. We illustrate the physical meaning of the method and we show how the block longitudinal dispersivity approaches, under certain conditions, the Scheidegger limit at large Péclet numbers. Lastly, we discuss the potential and limitations of the method to accurately describe dispersion in solute transport applications in heterogeneous aquifers.


[Patient with Peutz-Jeghers syndrome and liver metastases from an unknown primary tumor].
In a 35-year old man with deep venous thrombosis liver metastases of an adenocarcinoma were observed. The primary tumour was not found. The patient had pigmentations on the lips and hamartomatous polyposis of the intestine. These findings indicate Peutz-Jeghers syndrome. In this syndrome there is an increased risk of, notably, gastrointestinal malignancy at an early age. Recent investigations have shown that Peutz-Jeghers syndrome is associated with a mutation in the STK11 gene on chromosome 19.


Comparative proteomic analysis of soybean nodulation using a supernodulation mutant, SS2-2.
Legumes have the ability to form root nodules that fix atmospheric nitrogen through a symbiotic interaction with nitrogen-fixing bacteria. As a first step in dissecting the molecular process of nodulation, proteome reference maps of soybean roots and nodules were constructed. Time course analysis revealed that the transition from root to nodule was accompanied with downregulation of defense-response related proteins, including Mn-superoxide dismutase, peroxidase (Prx), PR10, and stress-induced protein, leading to the initiation of a symbiotic interaction between the two partners. Following nitrogenase biosynthesis, the host plant cooperated with the rhizobia to fix atmospheric nitrogen under microaerobic conditions via expression of leghemoglobins and antioxidant proteins. Comparative proteome analysis indicated lower expression of malate dehydrogenase (MDH), leghemoglobins and nitrogenase in the nodule development of the supernodulation mutant, SS2-2, as compared to the wild type, indicating that SS2-2 forms functionally immature nodules in higher numbers with the lower activity of nitrogen fixation.


Contralateral effect of short-duration unilateral neuromuscular electrical stimulation and focal vibration in healthy subjects.
The "contralateral effect" phenomenon refers to the strength gain in the opposite, untrained homonymous muscle following unilateral training. Previous studies showed that neuromuscular electrical stimulation (NMES) of the right quadriceps facilitated maximal voluntary strength and efferent neural drive of the left knee extensors, while no previous study investigated the contralateral effect elicited by focal muscle vibration. The aim of this study was to investigate whether quadriceps NMES and focal vibration, when applied unilaterally, have the same potential to enhance the contralateral muscle strength and the associated neural drive. Randomized controlled experimental study. University laboratory. Healthy subjects. Subjects completed several maximal voluntary contractions (MVCs) of the left quadriceps (tested muscle) while the right quadriceps (treated muscle) received no conditioning stimulation (control condition), NMES or focal vibration. Paired supramaximal stimuli were delivered to the left quadriceps during and immediately after the MVCs to assess voluntary activation. The EMG activity of vastus lateralis, vastus medialis, and rectus femoris muscles of the left quadriceps was also concomitantly recorded. MVC torque and voluntary activation of the left quadriceps increased during contralateral NMES and vibration. A remarkable inter-individual variability was observed in the contralateral effect of NMES and vibration. In fact, MVC and voluntary activation increases were particularly evident in subjects "responders" to both treatments (who showed NMES-elicited increases in MVC and voluntary activation of 22.5% and 15.8%, respectively, and vibration-elicited increases of 13.1% and 10.7%, respectively). Moreover, we found that the increases in voluntary activation and EMG activity elicited by NMES were higher than those elicited by focal vibration. We also found that voluntary activation increases were higher in subjects presenting lower baseline levels of voluntary activation. The short-duration unilateral application of quadriceps NMES and focal vibration increased MVC torque and efferent neural drive of the contralateral homologous muscle in healthy subjects. As the two physical therapy modalities can be useful to maximize motor unit recruitment contralaterally to the side of application, they could be incorporated in rehabilitation protocols when unilateral voluntary contractions are uncomfortable, painful or not feasible.


Distinct Proteomic, Transcriptomic, and Epigenetic Stress Responses in Dorsal and Ventral Hippocampus.
Acutely stressful experiences can trigger neuropsychiatric disorders and impair cognitive processes by altering hippocampal function. Although the intrinsic organization of the hippocampus is highly conserved throughout its long dorsal-ventral axis, the dorsal (anterior) hippocampus mediates spatial navigation and memory formation, whereas the ventral (posterior) hippocampus is involved in emotion regulation. To understand the molecular consequences of stress, detailed genome-wide screens are necessary and need to distinguish between dorsal and ventral hippocampal regions. While transcriptomic screens have become a mainstay in basic and clinical research, proteomic methods are rapidly evolving and hold even greater promise to reveal biologically and clinically relevant biomarkers. Here, we provide the first combined transcriptomic (RNA sequencing) and proteomic (sequential window acquisition of all theoretical mass spectra [SWATH-MS]) profiling of dorsal and ventral hippocampus in mice. We used three different acute stressors (novelty, swim, and restraint) to assess the impact of stress on both regions. We demonstrated that both hippocampal regions display radically distinct molecular responses and that the ventral hippocampus is particularly sensitive to the effects of stress. Separately analyzing these structures greatly increased the sensitivity to detect stress-induced changes. For example, protein interaction cluster analyses revealed a stress-responsive epigenetic network around histone demethylase Kdm6b restricted to the ventral hippocampus, and acute stress reduced methylation of its enzymatic target H3K27me3. Selective Kdm6b knockdown in the ventral hippocampus led to behavioral hyperactivity/hyperresponsiveness. These findings underscore the importance of considering dorsal and ventral hippocampus separately when conducting high-throughput molecular analyses, which has important implications for fundamental research as well as clinical studies.


Anti-tuberculosis activities of the crude methanolic extract and purified fractions of the bulb of Crinum jagus.
Tuberculosis (TB) is of great public health burden globally especially in developing countries of Africa and Asia . Current TB regimen involves multiple therapies and of long duration leading to poor patient adherence. There is also the challenge of multidrug resistant TB. Hence, there is a need for discovery of new anti- TB drugs. This study was designed to investigate the in -vitro activity of the crude methanolic extract and chromatographic fractions of the bulb of Crinum jagus against Mycobacterium tuberculosis isolates. The extracts were screened for anti- TB activity against three different M. tuberculosis isolates and a drug susceptible reference strain H37Rv using Lowenstein Jensen (L-J) medium and Middlebrook 7H10agar. The crude extract was prepared using soxhlet extraction apparatus while the purified fractions were obtained by column chromatography. The two media were inoculated with M. tuberculosis strains, after which the crude and purified extracts were added. After 4-6 weeks incubation, colony forming units were counted and percentage inhibition calculated. The crude extract and the purified fractions showed inhibitory activity on all the isolates tested including the reference strain. Fraction 3 showed the highest inhibitory percentage (86%) among the extracts. At a concentration of 1.0mg/ml, the percentage inhibition of fraction 3, rifampicin and isoniazid against M. tuberculosis strain 3 were 83%, 95% and 86% in L-J medium respectively while 86%, 96% and 89% were obtained respectively in Middle brook medium. Results showed that the crude methanolic extract and the purified fractions of the bulb of Crinum jagus exhibited anti-mycobacterial activity which is an indication of promising potential of this plant for the development of anti-tuberculosis agent.