Radial microbrain form of micrencephaly: possible association with carbamazepine.
A premature infant exposed to carbamazepine in utero had a markedly undersized brain on cranial ultrasonogram. Postmortem examination of the brain revealed no evidence of hypoxic-ischemic injury, hemorrhage, infarction, congenital infection, or calcification. The normal cortical gyral pattern, normal residual germinal matrix, and normal cortical lamination suggested the diagnosis of a radial microbrain form of micrencephaly.


New alk genes detected in Antarctic marine sediments.
Alkane monooxygenases (Alk) are the key enzymes for alkane degradation. In order to understand the dispersion and diversity of alk genes in Antarctic marine environments, this study analysed by clone libraries the presence and diversity of alk genes (alkB and alkM) in sediments from Admiralty Bay, King George Island, Peninsula Antarctica. The results show a differential distribution of alk genes between the sites, and the predominant presence of new alk genes, mainly in the pristine site. Sequences presented 53.10-69.60% nucleotide identity and 50.90-73.40% amino acid identity to alkB genes described in Silicibacter pomeroyi, Gordonia sp., Prauserella rugosa, Nocardioides sp., Rhodococcus sp., Nocardia farcinica, Pseudomonas putida, Acidisphaera sp., Alcanivorax borkumensis, and alkM described in Acinetobacter sp. This is the first time that the gene alkM was detected and described in Antarctic marine environments. The presence of a range of previously undescribed alk genes indicates the need for further studies in this environment.


Validating self-report of diabetes use by participants in the 45 and Up Study: a record linkage study.
Prevalence studies usually depend on self-report of disease status in survey data or administrative data collections and may over- or under-estimate disease prevalence. The establishment of a linked data collection provided an opportunity to explore the accuracy and completeness of capture of information about diabetes in survey and administrative data collections. Baseline questionnaire data at recruitment to the 45 and Up Study was obtained for 266,848 adults aged 45 years and over sampled from New South Wales, Australia in 2006-2009, and linked to administrative data about hospitalisation from the Admitted Patient Data Collection (APDC) for 2000-2009, claims for medical services (MBS) and pharmaceuticals (PBS) from Medicare Australia data for 2004-2009. Diabetes status was determined from response to a question 'Has a doctor EVER told you that you have diabetes' (n = 23,981) and augmented by examination of free text fields about diagnosis (n = 119) or use of insulin (n = 58). These data were used to identify the sub-group with type 1 diabetes. We explored the agreement between self-report of diabetes, identification of diabetes diagnostic codes in APDC data, claims for glycosylated haemoglobin (HbA1c) in MBS data, and claims for dispensed medication (oral hyperglycaemic agents and insulin) in PBS data. Most participants with diabetes were identified in APDC data if admitted to hospital (79.3%), in MBS data with at least one claim for HbA1c testing (84.7%; 73.4% if 2 tests claimed) or in PBS data through claim for diabetes medication (71.4%). Using these alternate data collections as an imperfect 'gold standard' we calculated sensitivities of 83.7% for APDC, 63.9% (80.5% for two tests) for MBS, and 96.6% for PBS data and specificities of 97.7%, 98.4% and 97.1% respectively. The lower sensitivity for HbA1c may reflect the use of this test to screen for diabetes suggesting that it is less useful in identifying people with diabetes without additional information. Kappa values were 0.80, 0.70 and 0.80 for APDC, MBS and PBS respectively reflecting the large population sample under consideration. Compared to APDC, there was poor agreement about identifying type 1 diabetes status. Self-report of diagnosis augmented with free text data indicating diabetes as a chronic condition and/or use of insulin among medications used was able to identify participants with diabetes with high sensitivity and specificity compared to available administrative data collections.


Use of generalised additive models to categorise continuous variables in clinical prediction.
In medical practice many, essentially continuous, clinical parameters tend to be categorised by physicians for ease of decision-making. Indeed, categorisation is a common practice both in medical research and in the development of clinical prediction rules, particularly where the ensuing models are to be applied in daily clinical practice to support clinicians in the decision-making process. Since the number of categories into which a continuous predictor must be categorised depends partly on the relationship between the predictor and the outcome, the need for more than two categories must be borne in mind. We propose a categorisation methodology for clinical-prediction models, using Generalised Additive Models (GAMs) with P-spline smoothers to determine the relationship between the continuous predictor and the outcome. The proposed method consists of creating at least one average-risk category along with high- and low-risk categories based on the GAM smooth function. We applied this methodology to a prospective cohort of patients with exacerbated chronic obstructive pulmonary disease. The predictors selected were respiratory rate and partial pressure of carbon dioxide in the blood (PCO2), and the response variable was poor evolution. An additive logistic regression model was used to show the relationship between the covariates and the dichotomous response variable. The proposed categorisation was compared to the continuous predictor as the best option, using the AIC and AUC evaluation parameters. The sample was divided into a derivation (60%) and validation (40%) samples. The first was used to obtain the cut points while the second was used to validate the proposed methodology. The three-category proposal for the respiratory rate was ≤ 20;(20,24];> 24, for which the following values were obtained: AIC=314.5 and AUC=0.638. The respective values for the continuous predictor were AIC=317.1 and AUC=0.634, with no statistically significant differences being found between the two AUCs (p =0.079). The four-category proposal for PCO2 was ≤ 43;(43,52];(52,65];> 65, for which the following values were obtained: AIC=258.1 and AUC=0.81. No statistically significant differences were found between the AUC of the four-category option and that of the continuous predictor, which yielded an AIC of 250.3 and an AUC of 0.825 (p =0.115). Our proposed method provides clinicians with the number and location of cut points for categorising variables, and performs as successfully as the original continuous predictor when it comes to developing clinical prediction rules.


A theoretical study of the uncatalyzed and BF3-assisted Baeyer-Villiger reactions.
The mechanisms for the uncatalyzed and boron trifluoride (BF3) assisted Baeyer-Villiger reactions between acetone and hydrogen peroxide have been investigated using high level ab initio [MP2 and CCSD(T)] and density functional theory (B3LYP) methods. Both steps in the uncatalyzed reaction are found to have very high transition state energies. It is clear that detectable amounts of the Crieege intermediate or the products cannot be formed without the aid of a catalyst. The main function of BF3 in both the addition step and the rearrangement (migration) step is to facilitate proton transfer. In the addition step the complexation of hydrogen peroxide with BF3 leads to an increased acidity of the attacking OH group, while in the rearrangement step BF3 takes active part in the proton-transfer process. This latter step is found to be rate determining with an activation free energy of 17.7 kcal/mol in organic solution. The products of the reaction are BF2OH, hydrogen fluoride, and methyl acetate. Thus, BF3 is not directly regenerated from the reaction.


Experiences and perceptions of infant dental enucleation among Somali immigrants in Sweden: a phenomenographic study.
Objective: The aim of this study was to explore and describe ways of experiencing and perceiving the Eastern African practice of infant dental enucleation (IDE) among immigrants of Somali origin living in Sweden. Material and methods: Six informants, three men and three women aged 26-54 years, were recruited for semi-structured individual interviews. Phenomenographic analysis of the interview transcripts was performed. Findings: Informants described four ways of experiencing and perceiving IDE: as an effective, necessary treatment; as a disputed tradition; as an alternative to failure; and as a desperate measure. The experiences and perceptions were highly influenced by the contexts the informants had been in, namely, communities in which traditional treatments were used frequently, in which other people were influential over their daily lives, and in which negative experiences of formal health care were common, as well as other difficult circumstances beyond the informants' individual control. Conclusions: The findings contribute to deepened understanding of IDE and the importance of context to the practice of it. Further, the findings deepen understanding of the decision to have the practice performed on infants, which may help dental and health care personnel to adequately communicate with individuals of Somali origin about the harmfulness of IDE.


Amplifying the macromolecular crowding effect using nanoparticles.
The melting temperature (T(m)) of DNA is affected not only by salt but also by the presence of high molecular weight (MW) solutes, such as polyethylene glycol (PEG), acting as a crowding agent. For short DNAs in a solution of low MW PEGs, however, the change of excluded volume upon melting is very small, leading to no increase in T(m). We demonstrate herein that by attaching 12-mer DNAs to gold nanoparticles, the excluded volume change was significantly increased upon melting, leading to increased T(m) even with PEG 200. Larger AuNPs, higher MW PEGs, and higher PEG concentrations show even larger effects in stabilizing the DNA. This study reveals a unique and fundamental feature at nanoscale due to geometric effects. It also suggests that weak interactions can be stabilized by a combination of polyvalent binding and the enhanced macromolecular crowding effect using nanoparticles.


Hypnotic efficacy of diphenhydramine, methapyrilene, and pentobarbital.
The antihistamines diphenhydramine and methapyrilene were compared with pentobarbital for hypnotic effect in two Veterans Administration Hospital populations using subjective-response methods. In the first part of the study, 60 mg and 180 mg of pentobarbital were compared with 50 mg and 150 mg of diphenhydramine. A positive dose-response relationship was obtained only for pentobarbital; neither dose of diphenhydramine was significantly different from 60 mg of pentobarbital for any response variable. In the second part of the study, 100 mg of pentobarbital, 50 mg of diphenhydramine, and 50 mg of diphenhydramine, and 50 mg of methapyrilene were compared with placebo. One hundred mg of pentobarbital and 50 mg of diphenhydramine were significantly different from placebo, but 50 mg of methapyrilene was not.


Genetic variants and mutations of PPM1D control the response to DNA damage.
The Wip1 phosphatase is an oncogene that is overexpressed in a variety of primary human cancers. We were interested in identifying genetic variants that could change Wip1 activity. We identified 3 missense SNPs of the human Wip1 phosphatase, L120F, P322Q, and I496V confer a dominant-negative phenotype. On the other hand, in primary human cancers, PPM1D mutations commonly result in a gain-of-function phenotype, leading us to identify a hot-spot truncating mutation at position 525. Surprisingly, we also found a significant number of loss-of-function mutations of PPM1D in primary human cancers, both in the phosphatase domain and in the C terminus. Thus, PPM1D has evolved to generate genetic variants with lower activity, potentially providing a better fitness for the organism through suppression of multiple diseases. In cancer, however, the situation is more complex, and the presence of both activating and inhibiting mutations requires further investigation to understand their contribution to tumorigenesis.


Targeting the RNA splicing machinery as a novel treatment strategy for pancreatic carcinoma.
Aberrant patterns of pre-mRNA splicing have been established for many human malignancies, yet the mechanisms responsible for these tumor-specific changes remain undefined and represent a promising area for therapeutic intervention. Using immunohistochemistry, we have localized the expression of a central splicing regulator, serine-arginine protein kinase 1 (SRPK1), to the ductular epithelial cells within human pancreas and have further shown its increased expression in tumors of the pancreas, breast, and colon. Small interfering RNA-mediated down-regulation of SRPK1 in pancreatic tumor cell lines resulted in a dose-dependent decrease in proliferative capacity and increase in apoptotic potential. Coordinately, the disruption of SRPK1 expression resulted in enhanced sensitivity of tumor cells to killing by gemcitabine and/or cisplatin. A dose-dependent reduction in the phosphorylation status of specific SR proteins was detected following the down-regulation of SRPK1 and is likely responsible for the observed alterations in expression of proteins associated with apoptosis and multidrug resistance. These data support SRPK1 as a new, potential target for the treatment of pancreatic ductular cancer that at present remains largely unresponsive to conventional therapies. Furthermore, these results support the development of innovative therapies that target not only specific splice variants arising during tumorigenesis but also the splice regulatory machinery that itself may be abnormal in malignant cells.


Are there cervical spine findings at MR imaging that are specific to acute symptomatic whiplash injury? A prospective controlled study with four experienced blinded readers.
To compare the magnetic resonance (MR) imaging findings in patients with acute whiplash injury with those in matched control subjects. In a prospective multicenter controlled study, from 2005 to 2008, 100 consecutive patients underwent 1.5-T MR imaging examinations of the cervical spine within 48 hours after a motor vehicle accident. Findings in these patients were compared in a blinded fashion with those in 100 age- and sex-matched healthy control subjects. Four blinded independent readers assessed the presence of occult vertebral body and facet fractures, vertebral body and facet contusions, intervertebral disk herniations, ligamentum nuchae strains, ligamentum nuchae tears, muscle strains or tears, and perimuscular fluid. Accuracy (as compared with clinical findings) and interobserver reliability were calculated. Accuracy of MR imaging and interreader reliability were generally poor (sensitivity, 0.328; specificity, 0.728; positive and negative likelihood ratios, 1.283 and 1.084, respectively). MR imaging findings significantly associated with whiplash injuries were occult fracture (P<.01), bone marrow contusion of the vertebral body (P=.01), muscle strain (P<.01) or tear (P<.01), and the presence of perimuscular fluid (P<.01). While 10 findings thought to be specific for whiplash trauma were significantly (P<.01) more frequent in patients (507 observations), they were also regularly found in healthy control subjects (237 observations). There were no serious occult injuries that required immediate therapy. MR imaging at 1.5 T reveals only limited evidence of specific changes to the cervical spine and the surrounding tissues in patients with acute symptomatic whiplash injury compared with healthy control subjects.


Dietary flaxseed modulates the miRNA profile in irradiated and non-irradiated murine lungs: a novel mechanism of tissue radioprotection by flaxseed.
Dietary flaxseed (FS) displays antioxidant and anti-inflammatory properties in preclinical models of lung disease including radiation-induced pneumonopathy, however the mechanisms of lung radioprotection are incompletely understood. MicroRNAs (miRNAs) are short oligonucleotides that act as important posttranscriptional regulators of diverse networks including inflammatory response networks. Responses of miRNA profiles to diet and radiation exposure have been reported, but the potential contribution of miRNAs to diet-related radioprotection has never been tested. In this exploratory pilot study, mice were fed 10% FS or a 0% FS isocaloric control diet and exposed to a single-fraction 13.5 Gy thoracic X-ray radiation treatment (XRT). Lung RNA was extracted 48 h post-XRT and small RNAs profiled by OpenArray. FS significantly modulated expression of multiple miRNAs, including 7 with P<0.001. miR-150 was downregulated approximately 2.9-fold in the FS groups and is disproportionately integrated into immune response-related networks. Although few miRNAs were significantly changed by radiation, interaction between diet and radiation was observed. For example, miR-29c was greatly downregulated in the FS/Control group (10- to 50-fold) but slightly upregulated in the FS/radiation group. Compared with FS/control, the FS/radiation group experienced a 50% decrease of the p53-responsive miR-34a, which regulates senescence- and apoptosis-related factors. FS induced significant changes in lung miRNA profile suggesting that modulation of small RNA by dietary supplements may represent a novel strategy to prevent adverse side-effects of thoracic radiotherapy. This pilot study provides insight into a potential mechanism of flaxseed's radioprotection and provides a useful model-system to further explore and optimize such small RNA-based therapies.


Use of thermographic criteria to identify Raynaud's phenomenon in a population setting.
To assess the value of thermographic measurements of digital skin temperature after cold challenge in classifying Raynaud's phenomenon (RP) in a healthy population. One hundred seventy-five patients with RP and 404 controls were subjected to a 15 degrees C, 60 s cold challenge test. All participants were women. Digital temperature measurements were taken at baseline, immediately postimmersion, and 10 min after immersion using a portable radiometer. Baseline skin temperature was a significant predictor of RP; however, the fall in temperature on immersion and the subsequent rewarming rate provided no additional information. Baseline skin temperature can help to predict the occurrence of RP in patients drawn from the general population, but has relatively low discriminatory power. The cold challenge test itself is of limited additional value for classification. Although objective temperature measurements show little power overall to discriminate between RP and non-RP patients, detecting low baseline digital temperature may be a useful adjunct to clinical history in classifying the disease.


Properties of cytosolic epoxide hydrolase purified from the liver of untreated and clofibrate-treated mice. Characterization of optimal assay conditions, substrate specificity and effects of modulators on the catalytic activity.
We have characterized certain catalytic properties of cytosolic epoxide hydrolases purified from untreated and clofibrate-treated mouse liver. The enzyme activity was found to be sensitive to oxygen, but nitrogen-saturated buffers containing dithiothreitol maintained high activity for at least 12 h at 0 degrees C. Linearity of the hydration of trans-stilbene oxide with time and protein was established, the pH optimum was broad (6.5 to 7.4) and the temperature optimum was close to 50 degrees C for both forms. The activity was independent of ionic strength, with the exception of the control form in the absence of dithiothreitol, where a lower activity was observed at low ionic strength. The activity decreased when ethanol was replaced by acetone or acetonitrile as solvent for the substrate. Tetrahydrofuran was found to be highly inhibitory, while dimethylsulfoxide had less pronounced effects. The apparent Km values were 4.9 microM, 73 microM and 1980 microM for the control form with trans-stilbene oxide, cis-stilbene oxide and styrene oxide as substrates, respectively. The Km values for the enzyme from clofibrate-treated mice were in the same range, although the V values were higher for all three substrates with this form. The highest turnover was found for trans-beta-propylstyrene oxide as substrate, followed by trans-beta-ethylstyrene oxide. Little or no activity was observed with benzo[a]pyrene 4,5-oxide or cholesterol 5,6 alpha-oxide. The enzymes were found to be sensitive to 5,5'-dithiobis(2-nitrobenzoic acid) and a phenylmercuric salt. alpha-Naphthoflavone, beta-naphthoflavone and chalcone derivatives also inhibited the activity, while none of the compounds known to activate microsomal epoxide hydrolase activated the cytosolic forms.


[Method for determining the position of the catheter end in the central vein].
The position of the catheter end in the central vein was studied by the x-ray, ultrasonic, and electrometric methods during catheterization of 69 veins in 66 patients. The position was incorrect in 64% cases. Electrometric method for detecting the position of the end of venous catheter is the most available for intensive care wards of municipal hospitals, because no special equipment or staff is needed, the method is simple, can be used directly during catheterization, and is cheap.


[Effect of different doses of ultraviolet radiation on vitamin provision to the human body].
Exposure of healthy adults to prophylactic doses of UV-radiation in the medium- and long wavelength spectrum improved metabolism of vitamins A, E and D and increased their content in the body. UV-irradiation even in prophylactic doses increased ascorbic acid requirements. Excessive UV-irradiation produced an adverse effect on the vitamin content. However, the vitamin concentration in blood was not significantly decreased. This can be explained by the adaptation of the human body to UV-irradiation upon a continuous increase of its dosage.


A Method for the Synthesis of Thioindoles through Copper-Catalyzed C-S Bond Coupling Reaction.
We herein report the copper-catalyzed C-S bond coupling reaction of indoles with N-thiosuccinimides, resulting in moderate to excellent yields of mono- and bis-sulfenylated compounds such as arylthioindoles, alkylthioindoles, selenylated indoles, and cysteine-substituted indoles. Thioarylation and thioglycosylation at the C2 position of indole alkaloids in the Radix Isatidis were achieved via structural modification. The first total syntheses of isatindigotindolosides III and IV have been successfully carried out. The electrophilic sulfenyl bromides generated in situ can play an important role in the catalytic cycle.


Factors Associated With Receipt of Crosslinking for Keratoconus.
The aim of this study was to identify factors associated with receipt of standard fluence epithelium-off crosslinking (CXL) for keratoconus (KCN). This retrospective, cross-sectional study reviewed electronic health records of treatment-naive patients with KCN seen at the Wilmer Eye Institute between January 2017 and September 2020. Tomographic data were derived from Pentacam (Oculus, Wetzlar, Germany) devices. Multivariable population-average model using generalized estimating equations adjusting for age, sex, race, national area deprivation index, vision correction method, and disease severity was used to identify factors associated with receipt of CXL. From 583 patients with KCN, 97 (16.6%) underwent CXL for KCN. Patients who received CXL in at least 1 eye were significantly younger (mean 24.0 ± 7.8 years) than patients who had never undergone CXL (33.4 ± 9.3 years) (P < 0.001). In multivariable analysis, Black patients had 63% lower odds of receiving CXL for KCN (OR: 0.37, 95% CI, 0.18-0.79) versus White patients, and older age was protective against receipt of CXL (OR: 0.89 per 1-year increase, 95% CI, 0.86-0.93). Comparison of characteristics by race demonstrated that Black patients presented with significantly worse vision, higher keratometric indices (K1, K2, and Kmax), and thinner corneal pachymetry at baseline versus White or Asian patients. In this clinical cohort of patients with KCN from a tertiary referral center, Black patients were less likely to receive CXL presumably because of more advanced disease at presentation. Earlier active population screening may be indicated to identify and treat these patients before they become ineligible for treatment and develop irreversible vision loss. Such strategies may improve health equity in KCN management.


[Kidney procurement and transplantation from a surgical perspective].
Kidney transplantation is the best therapeutic option in many patients with end-stage renal disease, because it significantly increases lifespan over that of patients who remain on dialysis. Because of organ shortage the average waiting time for a suitable kidney in Germany is about four years after the onset of dialysis treatment. Currently about 80% of all transplanted kidneys are obtained from brain-dead patients. The possibility for kidney transplantation after living donation reduces the minimum waiting time to a few weeks. An optimized organizational strategy as well as donor and recipient preparation are possible in living donation, resulting in excellent transplant quality and a short cold-ischemia time. Pre-emptive kidney transplantation after living donation is an attractive treatment option without the need for previous dialysis and is also an option for children. The excellent long-term results after kidney transplantation have been caused by improvement of operative technique, organizational strategy, donor preparation, postoperative care and, in particular, immunosuppression.


Structural equation modeling of approval voting data.
The method of approval voting is a commonly used voting procedure in which each judge selects a subset of the alternatives. By postulating that the random utilities associated with the choice options in approval voting elections follow a multivariate normal distribution under the Thurstonian framework, Regenwetter, Ho, and Tsetlin (2007) attempted to integrate the normative theories and individual variabilities in modeling social behavior. However, their approach is limited to only three alternatives, due to computational intractability as the number of alternatives increases. In this article, we reparameterize extensions of their models under the structural equation modeling framework and propose the use of limited information methods for estimating model parameters. As a result, we are able to extend their previous approach to the analysis of approval voting data with any number of alternatives. Two applications are presented to illustrate the usefulness of such an approach.


Nonoptic pathway tumors in children with neurofibromatosis type 1.
To define the radiologic features and natural history of nonoptic pathway tumors (non-OPTs) in children with neurofibromatosis type 1 (NF1). We performed a retrospective cross-sectional analysis of 64 children with NF1 harboring 100 probable non-OPTs. Age at diagnosis, sex, tumor location, number of tumors, symptomology, concurrent OPT, radiographic progression (defined as qualitative and quantitative increases in size), and treatment were assessed. Tumor volumes were measured from initial presentation until treatment or end of disease progression. Sixty-three percent of probable non-OPTs progressed over time, where radiographic progression was concomitantly associated with clinical progression. Fifty-two percent of patients had incidentally identified probable non-OPTs. Twenty-five percent of patients were symptomatic at initial diagnosis, all of whom harbored tumors that grew on subsequent scans and required tumor-directed therapy. There were no clinical differences between probable non-OPTs localized to the brainstem vs other locations with respect to age, sex, concurrent optic pathway glioma, symptomology, and treatment. The average time from diagnosis to stabilization or decrease in tumor size was 2.34 years (SD, 2.15 years). Nineteen biopsied lesions were all histopathologically confirmed as tumor. Six children (9%) had deep extensive tumors, who presented earlier (mean age at diagnosis, 3.88 years), required multiple treatments, and had a shorter mean progression-free survival (48 months). Over half of children with NF1 in this study developed probable non-OPTs, the majority of which were clinically and radiographically progressive. While brainstem and nonbrainstem gliomas share similar clinical features and natural history, deep extensive tumors comprise a distinct aggressive group of tumors that warrant close attention.


Label-free imaging of biomolecules in food products using stimulated Raman microscopy.
The development of methods that allow microscale studies of complex biomaterials based on their molecular composition is of great interest to a wide range of research fields. We show that stimulated Raman scattering (SRS) microscopy is an excellent analytical tool to study distributions of different biomolecules in multiphasic systems. SRS combines the label-free molecular specificity of vibrational spectroscopy with an enhanced sensitivity due to coherent excitation of molecular vibrations. Compared to previous imaging studies using coherent anti-Stokes Raman scattering microscopy, the main advantage of SRS microscopy is the absence of the unwanted nonresonant background, which translates into a superior sensitivity and undistorted vibrational spectra. We compare spectra of complex materials obtained with stimulated Raman scattering and spontaneous Raman scattering in the crowded fingerprint region.We find that, as expected, there is excellent correspondence and that the SRS spectra are free from interference from background fluorescence. In addition, we show high-resolution imaging of the distributions of selected biomolecules, such as lipids and proteins, in food products with SRS microscopy.


Parents' experiences of donation to their child before kidney transplantation: A qualitative study.
To explore parents' experiences of donation to their child before kidney transplantation. Transplantation is the treatment of choice for paediatric patients with end-stage renal disease. Living donor kidney transplantation has shown a higher long-term transplant survival compared to deceased donor transplantation and entails a more controllable process, with shorter waiting time. Besides complex care and treatment of their child, parents must reflect on the prospects of being a donor for their child. However, little is known about the parent donor and parent caregiver perspective. A qualitative exploratory study taking a phenomenological-hermeneutic approach. The study was conducted in a Danish university hospital. Interviews were conducted with the parents of seven children, aged between 5-15 years, with end-stage renal disease in the period before kidney transplantation. Data were analysed with inspiration from Ricoeur's theory of interpretation on three levels: naïve reading, structural analysis and critical interpretation and discussion. The decision about donation was experienced as a matter of course and commitment. There were preferences for a kidney from a living donor, including the hope of being accepted as a donor. Being refused as a donor revealed feelings of powerlessness. However, transformation was performed into having a new role providing care and comfort to the child during the transplant process. Asking family and friends about donation could feel like crossing a line. The prospect of donating to one's child had an impact on the well-being of the entire family. Parents were in a vulnerable situation and in need of support, regarding both living and deceased donation. Waiting time included hopeful thoughts and reflections on a new caregiver role for the child during transplantation. Health professionals' attention, engagement and dialogue are essential in order to gain extensive and varied knowledge about the individual parent's experiences and the well-being of the entire family to provide care and support before, during and after the donation and transplantation process.


MicroRNA let-7 modulates the immune response to Mycobacterium tuberculosis infection via control of A20, an inhibitor of the NF-κB pathway.
The outcome of the interaction between Mycobacterium tuberculosis (Mtb) and a macrophage depends on the interplay between host defense and bacterial immune subversion mechanisms. MicroRNAs critically regulate several host defense mechanisms, but their role in the Mtb-macrophage interplay remains unclear. MicroRNA profiling of Mtb-infected macrophages revealed the downregulation of miR-let-7f in a manner dependent on the Mtb secreted effector ESAT-6. We establish that let-7f targets A20, a feedback inhibitor of the NF-κB pathway. Expression of let-7f decreases and A20 increases with progression of Mtb infection in mice. Mtb survival is attenuated in A20-deficient macrophages, and the production of TNF, IL-1β, and nitrite, which are mediators of immunity to Mtb, is correspondingly increased. Further, let-7f overexpression diminishes Mtb survival and augments the production of cytokines including TNF and IL-1β. These results uncover a role for let-7f and its target A20 in regulating immune responses to Mtb and controlling bacterial burden.


Stem cell factor and c-kit are expressed by and may affect vascular SMCs through an autocrine pathway.
Stem cell factor (SCF) is a membrane-bound and soluble growth factor that activates the c-kit tyrosine kinase receptor. Given the similarities between c-kit and platelet-derived growth factor (PDGF) receptors, we hypothesized that similar to PDGF, SCF/c-kit signaling may play a role in smooth muscle cell (SMC) function and thus the development of intimal hyperplasia. Human saphenous vein SMCs were harvested from veins procured at the time of bypass grafting. Carotid arteries from rats that were balloon injured (n = 12) at variable time points were compared to sham-operated controls (n = 3). Expression of SCF and c-kit was measured by immunohistochemistry (IHC) and Western blotting. Western blotting revealed that human SMCs express membrane-bound SCF. In separate experiments, we found that this growth factor undergoes proteolytic cleavage to its soluble form following exposure to matrix metalloproteinase-9 (MMP-9), a ubiquitous MMP released at the time of arterial injury. We next evaluated in human SMCs, expression of the SCF receptor, c-kit. Western blotting of human SMC lysates revealed minor but consistent expression of c-kit. IHC demonstrated c-kit expression to be localized to the media. To determine if c-kit is up-regulated during the development of intimal hyperplasia, we evaluated expression of this receptor in a rat carotid balloon injury model. Quantification of IHC staining on injured vessels revealed that c-kit expression within the media was significantly increased at 3, 7, 14, and 28 days following injury (28.1, 30.8, 16, and 10.4% increase over sham controls, respectively, P < 0.05). Furthermore, c-kit expression was prominent within the neointima and maximal at 7 days (53.4 +/- 7.8% of area c-kit positive). Human vascular SMCs express the growth factor SCF and its receptor, c-kit. SCF is released from its membrane-bound form via MMP-9. This finding and the dramatic increase in c-kit expression observed in the rat carotid artery after balloon injury suggests SCF/c-kit signaling may affect SMC function via an autocrine pathway.


Managed care in Eastern Europe: an opportunity for U.S. firms.
Health care in Eastern Europe is in transition; the former state-run health systems are in shambles. This article describes elements of these systems, discusses transition problems, such as corruption, and suggests areas in which American firms can prosper. Problems with capital development and red tape will need to be overcome. However, the quality of physician training is high, and many doctors are eager to work with American institutions to emulate their standards of care. Their need for training in Western management techniques is quite apparent. The author suggests that managed care organizations can be established rapidly if local partners are included in their development.


Comparison of organically and conventionally produced Batavia type lettuce stored in modified atmosphere packaging for postharvest quality and nutritional parameters.
The impacts of organic and conventional production systems on postharvest life and quality parameters of Batavia type 'Caipira' lettuce heads (Lactuca sativa L.) were investigated. Harvested lettuce heads grown in two different production systems were stored at 0 °C temperature and 95-98% relative humidity for 20 days in modified atmosphere packaging. The lowest weight loss, the highest ascorbic acid content and antioxidant activity were obtained from the organic production system (Org-2). The conventional production system had higher total soluble solids, titratable acidity, and total phenolic contents. During the shelf-life period at 20 °C, the weight losses of lettuce heads grown conventionally were higher than with the other production system. Conventionally grown heads had higher titratable acidity and total phenolic contents than organically grown heads. The highest titratable acidity and h° values were obtained from the plants grown under conventional and organic production systems (Org-2), while the highest chroma value and antioxidant activity were detected from the control treatment. The highest ascorbic acid content was detected in the control treatment, but the effects of control, organic (Org-2) and conventional production systems on ascorbic acid content were not statistically significant. The results indicated that the organic production system (Org-2) was the most effective treatment in prolonging postharvest life and protecting the quality of Batavia type 'Caipira' lettuce heads stored in modified atmosphere packaging. © 2018 Society of Chemical Industry.


Acute myocardial infarction in an 80 year-old woman caused by left main occlusion with concomitant chronic total occlusions of right and left coronary artery: successful treatment with percutaneous revascularization.
Although acute left main coronary artery occlusion is rare, it carries a very high mortality rate. Following the encouraging results of trials testing the effect of primary percutaneous coronary intervention, more cases of left main stenosis are treated as culprit lesion in acute myocardial infarction. Few cases of primary percutaneous intervention on left main occlusion have been published. We present the case of an elderly patient presenting with acute myocardial infarction complicated by cardiogenic shock due to left main occlusion, with concomitant chronic total occlusion of right and left anterior descending coronary arteries. Successful percutaneous intervention as a bridge to coronary artery bypass grafting was performed with stent implantation, which resulted in the relief of obstruction, the restoration of blood flow and the immediate clinical improvement of the patient. The patient left the hospital in good condition after 11 days, although she had refused the proposed coronary artery bypass grafting.


Vitrified turkey ovarian tissue cultured and assessed through gene expression patterns: A potential screening tool.
Biobanking of turkey ovarian tissue has the potential to play a crucial part in preserving female genetics. To date, ovarian tissue has only been vitrified using a standard protocol, with immediate analyses after warming, therefore, long-term cryoinjury is unknown. Long-term cryoinjury was investigated here by in-ovo culturing, fresh (non-vitrified), a purposefully suboptimal poor vitrification (PV), and the standard vitrified (StV) protocol. Assessments were performed via cellular morphological changes and mRNA gene expression differences, immediately (day 0) or after 2, 4, or 6 days of in-ovo culturing. On day 0, the mRNA levels of heat-shock protein A2 (HSPA2) were lowest in the fresh tissue, and increased 5-fold in the StV treatment, and 18-fold in the PV treatment. Whereas, by day 6, growth determining factor 9 (GDF9) mRNA levels within the fresh tissue were over 3-fold and 21-fold higher than StV and PV treatments, respectively. After 6 days of in-ovo culture the follicle density was highest in the fresh ovarian tissue (4701 ± 950 #/mm3), followed by the StV (1601 ± 300 #/mm3), with PV having the lowest density (172 ± 145 #/mm3). This shows that although the density of follicles was higher in StV versus PV, a considerable number (∼65 %) were lost compared to the fresh treatment. Additionally, the HSPA2 expression could be an early screening tool, whereas GDF9 expression could be a late screening tool, used to assess turkey ovarian tissue vitrification protocols. We conclude that the StV protocol should be further optimized to try and improve follicle numbers post-warming.


Effect of Coffee Silver Skin and Brewers' Spent Grain in the Control of Root-knot Nematodes.
Plant parasitic nematodes (PPN) are important pests of numerous agricultural crops especially vegetables, able to cause remarkable yield losses correlated to soil nematode population densities at sowing or transplant. The concern on environmental risks, stemming from the use of chemical pesticides acting as nematicides, compels to their replacement with more sustainable pest control strategies. To verify the effect of aqueous extracts of the agro-industry waste coffee silverskin (CS) and brewers' spent grain (BSG) on the widespread root-knot nematode Meloidogyne incognita, and on the physiology of tomato plants, a pot experiment was carried out in a glasshouse at 25 ± 2 °C. The possible phytotoxicity of CS and BSG extracts was assessed on garden cress seeds. Tomato plants (landrace of Apulia Region) were transplanted in an artificial nematode infested soil with an initial population density of 3.17 eggs and juveniles/mL soil. CS and BSG were applied at rates of 50 and 100 % (1L/pot). Untreated and Fenamiphos EC 240 (nematicide) (0.01 μL a.i./mL soil) treated plants were used as controls. Reactive oxygen species (ROS) and chlorophyll content of tomato plants were estimated during the experiment. CS extract, at both doses, significantly reduced nematode population in comparison to the untreated control, although it was less effective than Fenamiphos. BSG extract did not reduce final nematode population compared to the control. Ten days after the first treatment, CS 100 %, BSG 50 % and BSG 100% elicited the highest ROS values, which considerably affected the growth of tomato plants in comparison to the untreated plants. The control of these pests is meeting with difficulties because of the current national and international regulations in force, which are limiting the use of synthetic nematicides. Therefore, CS extracts could assume economic relevance, as alternative products to be used in sustainable strategies for nematode management.


Ambulatory Behavior Assessment Using Deep Learning.
This work leverages a custom implementation of a deep neural network-based object detection algorithm to detect people and a set of assistive devices relevant to clinical environments. The object detections form the basis for the quantification of different ambulatory activities and related behaviors. Using features extracted from detected people and objects as input to machine learning models, we quantify how a person ambulates and the mode of ambulation being used.Clinical relevance- This system provides the data required for clinicians and hospitalized patients to work together in the creation, monitoring, and adjustment of ambulatory goals.


Disruption of the human papillomavirus type 16 E2 gene protects cervical carcinoma cells from E2F-induced apoptosis.
Human papillomavirus type 16 (HPV-16) is a DNA tumour virus that has been implicated in the development of cervical cancer. In non-transformed HPV-infected cells, the HPV E2 protein regulates transcription of the viral E6 and E7 oncogenes. Malignant transformation is usually accompanied by disruption of the E2 gene and consequent deregulated expression of E6 and E7. Here we show that re-introduction of the HPV-16 E2 protein into an HPV-16-transformed cervical carcinoma cell line results in a decrease in growth rate and, in the absence of serum growth factors, cell death via apoptosis. E2 expression increases E6/E7 mRNA levels. This brings about an increase in E7 protein levels, which in turn leads to an increase in free E2F, a condition that has previously been shown to induce apoptotic cell death. Despite the increase in E6 mRNA there is no detectable E6 protein in these cells and E2 expression does not reduce the activity of a p53-responsive promoter. Our data suggest that disruption of the E2 gene produces HPV-transformed cells that are less liable to undergo apoptosis and, therefore, more likely to form cervical tumours.


Effect of diuretics on ureteral stone therapy with extracorporeal shock wave lithotripsy.
To evaluate the effect of diuretics on ureteral stone fragmentation and clearance during therapy with extra corporeal shock wave lithotripsy (ESWL), we studied 87 patients with ureteral stone at different levels and treated with ESWL. The patients were randomized into two groups treated by standard ESWL; the treatment protocol included 3500 shock wave per patient in each session, energy of the shock in two groups was 13 to 9 kv per patient, and the number of sessions was 3 per patient. The first group included 43 patients who received only ESWL, while the second group of 44 patients received as well 40 mg of furosemide. Stone fragmentation rate was 81% and 93.1% and stone clearance rate was 68.2% and 88.4% for the first and the second groups, respectively. With diuretics, fragmentation was 18.8% more in the middle ureteral stones, 16.9% more in the upper tract stones, and 5.4% more in the distal stones. Moreover, clearance of fragmented stones was 38%, 28%, 15.4% more at middle and upper and distal ureteral stone, respectively. We conclude that the stone fragmentation and clearance were higher with ESWL and diuretics than without diuresis. Diuresis is safe and has some advantage at increasing the effect of ESWL on ureteral stones especially the middle ureteral calculi.


Microsurgical anatomy of the oculomotor cistern.
To define the characteristics of the arachnoidal sleeve and cistern that accompany the oculomotor nerve through the cavernous sinus roof. Forty cavernous sinuses were examined using 3 to 40x magnification. Information was obtained about the size of the oculomotor cistern and its relationship to the roof of the cavernous sinus and anterior clinoid process. An arachnoidal sleeve and cistern, referred to as the oculomotor cistern, accompanied the oculomotor nerve into the roof of all the cavernous sinuses examined. The oculomotor cistern extends from the oculomotor porus, where the nerve enters the roof of the cavernous sinus, to the area below the tip or the adjacent part of the lower margin of the anterior clinoid process. From the porus, the nerve passes forward and downward to the depth of the cistern where it becomes incorporated into the fibrous lateral wall of the cavernous sinus. The width of the cistern was maximal at the oculomotor porus averaged 5.5 mm (range, 3.0-9.2 mm), and tapered slightly towards the midpoint and deep end of the cistern. The cistern's average length was 6.5 mm (range, 3.0-11.0 mm). The oculomotor nerve usually coursed closer to the anterior than the posterior wall of the cistern at the level of the oculomotor porus. The oculomotor cistern, an arachnoidal and dural cuff, accompanies the oculomotor nerve through the cavernous sinus roof to the area just below or anterior to the lower edge of the tip of the anterior clinoid process. The segment of the nerve inside the oculomotor cistern is interposed between its free portion in the interpeduncular cistern and the part of its course where it is incorporated into the fibrous lateral wall of the cavernous sinus. The cistern can be opened to aid in the exposure and mobilization of the nerve in dealing with pathology in the area.


Concerted evolution of human amylase genes.
Cosmid clones containing 250 kilobases of genomic DNA from the human amylase gene cluster have been isolated. These clones contain seven distinct amylase genes which appear to comprise the complete multigene family. By sequence comparison with the cDNAs, we have identified two pancreatic amylase genes and three salivary amylase genes. Two truncated pseudogenes were also recovered. Intergenic distances of 17 to 22 kilobases separate the amylase gene copies. Within the past 10 million years, duplications, gene conversions, and unequal crossover events have resulted in a very high level of sequence similarity among human amylase gene copies. To identify sequence elements involved in tissue-specific expression and hormonal regulation, the promoter regions of the human amylase genes were sequenced and compared with those of the corresponding mouse genes. The promoters of the human and mouse pancreatic amylase genes are highly homologous between nucleotide -160 and the cap site. Two sequence elements thought to influence pancreas-specific expression of the rodent genes are present in the human genes. In contrast, similarity in the 5' flanking sequences of the salivary amylase genes is limited to several short sequence elements whose positions and orientations differ in the two species. Some of these sequence elements are also associated with other parotid-specific genes and may be involved in their tissue-specific expression. A glucocorticoid response element and a general enhancer element are closely associated in several of the amylase promoters.


Bisphosphonates for breast cancer.
Bone is the most common site of metastatic disease associated with breast cancer affecting more than half of women during the course of their disease. Bone metastases are a significant cause of morbidity due to pain, pathological fractures, hypercalcaemia and spinal cord compression, and contribute to mortality. Bisphosphonates, which inhibit osteoclast-mediated bone resorption, are standard care for tumour-associated hypercalcaemia, and have been shown to reduce bone pain, improve quality of life, and to delay skeletal events and reduce their number in patients with multiple myeloma. Several randomized controlled trials have evaluated the role of bisphosphonates in breast cancer. To assess the effect of bisphosphonates on skeletal events, bone pain, quality of life and survival in women with early and advanced breast cancer. Randomized controlled trials were identified using the specialized register maintained by the Cochrane Breast Cancer Group (the search was applied to the databases Medline, Central/CCTR, Embase, CancerLit, and included handsearches from a number of other relevant sources). See: Cochrane Collaboration Collaborative Review Group in Breast Cancer search strategy. Randomized controlled trials evaluating skeletal events in women with metastatic breast cancer and early breast cancer comparing: 1. treatment with a bisphosphonate with the same treatment without a bisphosphonate 2. treatment with one bisphosphonate with treatment with a different bisphosphonate. Studies were selected by two independent reviewers. Studies fulfilling the eligibility criteria were evaluated for quality, particularly concealment of allocation to randomized groups. Data were extracted from the published papers or abstracts independently by the two primary reviewers for each of the specified endpoints (skeletal events, bone pain, quality of life and survival). Data on skeletal events and survival were presented as numbers of events, risk ratios and ratios of event rates. Meta-analyses were based on the fixed-effects model (Mantel-Haenszel). Subjective qualitative ratings were used to summarize the quality of life and pain data. Twenty one randomized studies were included. All studies in advanced breast cancer included women with clinically evident bone metastases (osteolytic and/or mixed osteolytic/osteoblastic) by plain xray and/or radionucleotide bone scans. In nine studies that included 2189 women with advanced breast cancer and existing bone metastases, bisphosphonates reduced the risk of developing a skeletal event by 17% (RR 0.83; 95% confidence interval (CI) 0.78-0.89; P < 0.00001). This effect was more modest, but still highly significant if episodes of hypercalcaemia were excluded (10 studies, 2656 women, RR 0.85; 95% CI 0.79-0.91 P = 0.0001). Overall, intravenous bisphosphonates reduce the risk of developing a skeletal event by 17 % (95% CI 0.78-0.89) compared with oral bisphosphonates, which reduce the risk of developing a skeletal event by 16 % (95% CI 0.76-0.93). Of the currently available bisphosphonates, 4 mg IV zolendronate reduces the risk of developing a skeletal event by 41% (RR 0.59, 95% CI 0.42-0.82), compared with 33 % by 90 mg IV pamdronate (RR 0.77, 95% CI 0.69-0.87), 18 % by 6 mg IV ibandronate (RR 0.82, 95% CI 0.67-1.00), 14 % by 50mg oral ibandronate (RR 0.86, 95% CI 0.73-1.02) and 16 % by 1600 mg oral clodronate (RR 0.84, 95% CI 0.72-0.98). Compared with placebo or no bisphosphonate, with bisphosphonates the skeletal event rate was lower in all of 12 studies in women with clinically evident bone metastases (median reduction of 29%, range 14-48%); statistically significant reductions were reported in 10 trials (four intravenous pamidronate, two oral clodronate, one intravenous ibandronate and two oral ibandronate, a single intravenous zolendronate study). Studies of intravenous zolendronate, pamidronate and oral clodronate in women with advanced breast cancer and clinically evident bone metastases showed significant delays in the median time to a skeletal event. Event-free survival was also reported to be longer in women receiving 6 mg of ibandronate compared with controls. Compared with placebo or no bisphosphonate, with bisphosphonates significant improvements in bone pain were reported in seven studies (90 mg iv pamidronate, 4 mg iv zolendronate, 6 mg iv ibandronate, 1600 mg oral clodronate and 50 mg oral ibandronate). Eight studies tested the effect of bisphosphonates compared with placebo on patient-rated quality of life using a referenced scale. Improvements in global quality of life were reported in only the three studies of iv and oral ibandronate. Treatment with bisphosphonates does not appear to affect survival in women with advanced breast cancer. Intravenous zolendronate (4 mg) appeared to be as effective as pamidronate (90mg) when directly compared in a single randomized double-blind study, based on the risk of developing a skeletal related event, the median time to first skeletal event and skeletal morbidity rate (events per year). Updated re-evaluation of the primary data in the overall population, by multiple event analysis using the method of Anderson-Gill, showed a reduction in the risk of developing any skeletal complication (including hypercalcamia) of 20 % (zolendronate 4 mg compared with pamidronate 90 mg, RR = 0.80, 95% CI 0.66 - 0.97, p = 0.025), suggesting a possible advantage of zolendronate 4 mg compared with pamidronate 90 mg. In the three studies of bisphosphonates in 320 women with advanced breast cancer without clinically evident bone metastases, there was no significant reduction in the incidence of skeletal events (RR 0.99; 95% CI 0.67-1.47; P = 0.97). In the three studies of oral clodronate that included 1653 women with early breast cancer, there was no statistically significant evidence of reduction in the risk of developing skeletal metastases (RR 0.82; 95% CI 0.66-1.01; P = 0.07), or of visceral metastases (RR 0.95; 95% CI 0.80-1.12, p = 0.53). However there was evidence of improved survival (RR 0.82; 95% CI 0.69-0.97, p = 0.02). However there was statistically significant heterogeneity among these studies and a random effects meta-analysis emphasizes the uncertainty of this finding (RR 0.75; 95% CI 0.45 - 1.25; p = 0.19). Toxicity or adverse events were described in 18 of the 21 studies. In general, few serious adverse events were reported. Toxicity associated with bisphosphonates is generally mild and infrequent. Renal toxicity is the main issue with intravenous zolendronate and is dose (8 mg) and infusion time related (< 15 minutes). With daily oral calcium (500 mg) and vitamin D (300-400IU) no significant renal impairment or hypocalcamia was observed with a 15 minute infusion of 4 mg IV zolendronate compared with 90 mg pamidronate. Monitoring of renal function with every cycle of zolendronate was undertaken in all studies and is recommended in practice. No significant renal toxicity was observed with intravenous pamidronate or ibandronate. Mild gastrointestinal toxicity is the main toxicity with oral clodronate and oral ibandronate. In women with advanced breast cancer and clinically evident bone metastases, the use of bisphosphonates (oral or intravenous) in addition to hormone therapy or chemotherapy, when compared with placebo or no bisphosphonates, reduces the risk of developing a skeletal event and the skeletal event rate, as well as increasing the time to skeletal event. Some bisphosphonates may also reduce bone pain in women with advanced breast cancer and clinically evident bone metastases and may improve global quality of life. The optimal timing of initiation of bisphosphonate therapy and duration of treatment is uncertain. In women with early breast cancer the effectiveness of bisphosphonates remains an open question for research.


Assessment of the capability of a gelling complex made of tara gum and the exopolysaccharides produced by the microorganism Streptococcus thermophilus ST10 to prospectively restore the gut physiological barrier: a pilot study.
Leaky gut, or intestinal permeability, is the phenomenon of the gut wall exhibiting increased absorbency. It is pretty well recognised that an altered or damaged bowel lining or gut wall may result from unbalanced diet, parasites, infection, or medications and that this allows substances such as toxins, microbes, undigested food, or waste to leak through. As a natural consequence, this prompts the body to initiate an immune reaction leading to potentially severe health conditions. Different strategies may be used to improve, at least temporarily, the physiological intestinal barrier. The use of specific beneficial microorganisms, such as lactobacilli and bifidobacteria, has been suggested as an innovative tool to counteract an improper level of intestinal permeability. The association of bacteria with specific gelling agents, such as gums, may represent an improvement since these molecules are able to form hydrophilic gels that distribute uniformly over the inner intestinal surface. This pilot study was undertaken to evaluate intestinal permeability in subjects treated with a gelling complex, an association of tara gum and the microorganism Streptococcus thermophilus ST10 (DSM 25246), which has a well-demonstrated in vitro ability to synthesise and secrete exopolysaccharides (EPSs). Twenty-five healthy subjects were enrolled in this human intervention, double-blind, placebo-controlled, pilot trial (age between 21 and 57 y, mean 37.7±11.2). Subjects were then randomised into 2 groups: group A (13 subjects) was given an active formulation containing 250 mg of tara gum and 1 billion viable cells of S. thermophilus ST10, whereas group B (12 subjects) was given a placebo formulation. All the subjects participating in the study were directed to take 1 dose per day for 30 consecutive days. The presence and concentration of exopolysaccharides (EPSs) in the faeces was determined at time 0 (d0), after 30 days of treatment (d30), and at the end of the 2-week follow-up period (d45). The monosaccharide composition of EPSs was used to quantify the possible contribution of tara gum to the amount of polysaccharides detected in the faecal material. Intestinal permeability was evaluated at the same time by means of the lactitol/mannitol ratio (small intestine permeability) and sucralose concentration (colonic permeability) in urine specimens sampled after specified times. A statistical comparison was made between the concentration of EPSs, the lactulose/mannitol ratio, and the amount of excreted sucralose in the 2 groups at d0, d30, and d45. In the active group, supplementation with S. thermophilus ST10 and tara gum was able to significantly increase the faecal EPSs concentration compared with placebo (from 0.169 mg/g to 0.633 mg/g after 30 d, P<0.001). An interesting decrease in intestinal permeability, both of the small bowel and in the colon, was also recorded. The L/M ratio diminished from 0.021 in the active group to 0.014 and 0.015 after 30 and 45 days, respectively (P=0.045 and P=0.033 compared with placebo). The sucralose concentration decreased from 35.8 mg to 27.9 mg and 29.1 mg (P=0.038 and P=0.026 compared with placebo) at the end of the supplementation period and after the follow-up, respectively. No significant differences were recorded in the placebo after 30 days or at the end of the follow-up. The association of the EPSs produced by S. thermophilus ST10 and tara gum seems capable of significantly improving the intestinal functional barrier in healthy subjects. A wider study in subjects presenting impaired gut permeability would be useful in the future to confirm the positive results from this pilot trial. In any case, our findings are consistent with the parallel increase in exopolysaccharide concentration in the faecal material, thus suggesting the effective ability of the strain used to secrete EPSs in the gut lumen. An innovative approach of this type may be useful in helping to restore the physiological barrier by means of a merely natural and mechanical action.


DOMINATE Wounds.
Chronic wounds are a significant health problem worldwide. Often they are initially managed with various focal treatments until a specialist becomes involved, sometimes weeks or months after treatment has begun. Even at the specialist level, practices and guidelines are inconsistent due to a lack of high-level evidence. A disease management system for chronic wounds that is simple, practical, and adoptable by a variety of wound care practitioners is needed. Such a system would guide wound care providers to address the critical aspects of wound care in a prioritized, systematic sequence, leading to faster healing of simple wounds, and timely advancement to more complex therapies for wounds that require such treatment. This paper describes an empirically developed wound care management system that has been successfully implemented and provides evidence-based rationale for each of its components. Relatively simple and practical, this system organizes an approach to any type of wound, routine or complex.


Symptom Bother, Physical and Mental Stress, and Health-related Quality of Life in Women with Overactive Bladder Syndrome.
The objective of this study was to identify the relationships among symptom bother, physical and mental stress and health-related quality of life (HRQoL) in women with overactive bladder (OAB) syndrome. The participants were 106 women who were diagnosed with OAB (urgency, urge urinary incontinence, frequency, and/or nocturia) at P university hospital. Data were collected from Dec 23, 2011 to Aug 31, 2012. The mean score for symptom bother was 43.1 points, for physical stress, 12.8 which was slightly higher than mental stress (11.8), and for HRQoL, 63.9. For symptom type, there were statistically significant differences in the symptom bother (F=8.67, p<.001) and HRQL (F=3.32, p= .023). The Symptom bother of OAB was positively correlated with physical stress (r=.23, p= .014) and mental stress (r=.33, p<.001) and negatively correlated with the subscales of HRQoL; coping (r=-.66, p<.001), concern (r=-.71, p<.001), sleep (r=-.59, p<.001), and social interaction (r=-.58, p<.001). From the results, bother symptom was associated with physical, mental stress and HRQoL. These results suggest that nursing intervention programs for OAB should be developed not only to relieve the symptoms but also to reduce stress and improve the quality of life.


An Incremental Learning Framework to Enhance Teaching by Demonstration Based on Multimodal Sensor Fusion.
Though a robot can reproduce the demonstration trajectory from a human demonstrator by teleoperation, there is a certain error between the reproduced trajectory and the desired trajectory. To minimize this error, we propose a multimodal incremental learning framework based on a teleoperation strategy that can enable the robot to reproduce the demonstration task accurately. The multimodal demonstration data are collected from two different kinds of sensors in the demonstration phase. Then, the Kalman filter (KF) and dynamic time warping (DTW) algorithms are used to preprocessing the data for the multiple sensor signals. The KF algorithm is mainly used to fuse sensor data of different modalities, and the DTW algorithm is used to align the data in the same timeline. The preprocessed demonstration data are further trained and learned by the incremental learning network and sent to a Baxter robot for reproducing the task demonstrated by the human. Comparative experiments have been performed to verify the effectiveness of the proposed framework.


O-methylguanine-DNA methyltransferase (MGMT) mRNA expression predicts outcome in malignant glioma independent of MGMT promoter methylation.
We analyzed prospectively whether MGMT (O(6)-methylguanine-DNA methyltransferase) mRNA expression gains prognostic/predictive impact independent of MGMT promoter methylation in malignant glioma patients undergoing radiotherapy with concomitant and adjuvant temozolomide or temozolomide alone. As DNA-methyltransferases (DNMTs) are the enzymes responsible for setting up and maintaining DNA methylation patterns in eukaryotic cells, we analyzed further, whether MGMT promoter methylation is associated with upregulation of DNMT expression. ADULT PATIENTS WITH A HISTOLOGICALLY PROVEN MALIGNANT ASTROCYTOMA (GLIOBLASTOMA: N = 53, anaplastic astrocytoma: N = 10) were included. MGMT promoter methylation was determined by methylation-specific PCR (MSP) and sequencing analysis. Expression of MGMT and DNMTs mRNA were analysed by real-time qPCR. Prognostic factors were obtained from proportional hazards models. Correlation between MGMT mRNA expression and MGMT methylation status was validated using data from the Cancer Genome Atlas (TCGA) database (N = 229 glioblastomas). Low MGMT mRNA expression was strongly predictive for prolonged time to progression, treatment response, and length of survival in univariate and multivariate models (p<0.0001); the degree of MGMT mRNA expression was highly correlated with the MGMT promoter methylation status (p<0.0001); however, discordant findings were seen in 12 glioblastoma patients: Patients with methylated tumors with high MGMT mRNA expression (N = 6) did significantly worse than those with low transcriptional activity (p<0.01). Conversely, unmethylated tumors with low MGMT mRNA expression (N = 6) did better than their counterparts. A nearly identical frequency of concordant and discordant findings was obtained by analyzing the TCGA database (p<0.0001). Expression of DNMT1 and DNMT3b was strongly upregulated in tumor tissue, but not correlated with MGMT promoter methylation and MGMT mRNA expression. MGMT mRNA expression plays a direct role for mediating tumor sensitivity to alkylating agents. Discordant findings indicate methylation-independent pathways of MGMT expression regulation. DNMT1 and DNMT3b are likely to be involved in CGI methylation. However, their exact role yet has to be defined.


Characterising monitoring processes in event-based prospective memory: Evidence from pupillometry.
In event-based prospective memory (PM) paradigms, participants are engaged in an ongoing task (e.g. lexical decision) while maintaining an intention to produce a special response if they encounter pre-defined targets (e.g. animal words). This leads to slowed response times even on nontarget trials, which might be caused by: (A) a periodic or intermittent process that occurs transiently to check whether the current stimulus is a target, and/or (B) a sustained monitoring process maintained throughout task performance rather than being time-locked to stimulus presentation. These processes are hard to distinguish, seeing as the key difference between them occurs in the gap between trials. Processes occurring in these gaps cannot be measured directly by behavioural methods. Here we measured pupil size as a continuous index of intention-related processing in an event-based prospective memory task. Participants performed a lexical decision task while remembering intentions based on either specific target words or categories (e.g. animal words). In two experiments, response times were slowed during PM conditions. Pupil size was significantly increased in the category but not the specific-word condition. This effect was sustained throughout task performance rather than occurring transiently when stimuli were presented. Therefore there was no evidence for a transient pupillometric response associated with nontarget checking, although there was a strong transient response when targets were presented in either PM condition. These results provide evidence for a sustained PM monitoring process that occurs even in the gaps between trials.


Pheochromocytoma with Synchronous Ipsilateral Adrenal Cortical Adenoma.
Pheochromocytoma with synchronous ipsilateral adrenal cortical adenoma (PSCA) may present with mixed clinical, biochemical, and radiological features characteristic to each neoplasm subtype. All patients with a pathological diagnosis of pheochromocytoma were evaluated for an ipsilateral cortical adenoma from 1994 through 2015. Retrospectively extracted data included indications for adrenalectomy, diagnostic workup (biochemical and radiographic), operative characteristics, pathological findings, and postoperative complications. Sixteen of 413 patients (4%) undergoing adrenalectomy for pheochromocytoma had a PSCA. Median patient age was 57.7 years (IQR 50.1, 63.1); 50% were male. On imaging, 75% of the adrenal neoplasms were found incidentally and only 50% were reported to have a synchronous ipsilateral neoplasm based on imaging findings. Clinically important cortical hormone secretion was diagnosed in 38% of these patients; 25% had glucocorticoid secretory autonomy; and 13% had primary aldosteronism. Physicians should be aware that adrenal neoplasms with mixed diagnostic findings may represent PSCA. Evaluation should be performed on this co-occurrence to prevent perioperative complications from resection of an unexpected secretory cortical neoplasm.


Chemical synthesis and structure of the prokineticin Bv8.
Bv8, a 77-residue protein isolated from frogs, is the prototypic member of the prokineticin family of cytokines. Prokineticins (PKs) have only recently been identified in vertebrates (including humans), and they are believed to be involved in a number of key physiological processes, such as angiogenesis, neurogenesis, nociception, and tissue development. We used a combination of Boc solid-phase peptide synthesis, native chemical ligation, and in vitro protein folding to establish robust chemical access to this molecule. Synthetic Bv8 was obtained in good yield and exhibited full activity in a human neuroblastoma cell line and rat dorsal root ganglion (DRG) neurons. The 3D structure of the synthetic protein was determined by using NMR spectroscopy and it was found to be homologous with that of mamba intestinal toxin 1, which is the only other known prokineticin structure. Analysis of a truncated mutant lacking five residues at the N terminus that are critical for receptor binding and activation showed no perturbation to the core protein structure. Together with the functional data, this suggests that receptor binding is likely to be a highly cooperative process possibly involving major allosterically driven structural rearrangements. The facile and efficient synthesis presented here will enable preparation of unique chemical analogues of prokineticins, which should be powerful tools for modulating the structure and function of prokineticins and their receptors, and studying the many physiological processes that have been linked to them.


Emergency brake response time after first metatarsal osteotomy.
There is sparse information upon which to recommend a return to activity after foot surgery. The purpose of this study was to determine whether six weeks is sufficient time for the emergency brake response time to return to preoperative levels after a first metatarsal osteotomy for symptomatic hallux valgus. We conducted a prospective, observational study to assess the effect of surgery on emergency brake response time in a group of twenty-eight patients undergoing a unilateral first metatarsal osteotomy on the right side for symptomatic hallux valgus. A custom-made driving simulator was used to assess total brake response time, reaction time, and brake time. Patients were assessed preoperatively and at two and six weeks postoperatively. A control group of twenty-eight individuals matched for age, driving status, and sex was included for baseline comparison. Total brake response time, reaction time, and brake time were significantly lower for the control cohort compared with the preoperative values recorded in the study cohort (p < 0.05). Only seven of the twenty-eight study patients were able to complete the assessment at two weeks; the remainder were not able to complete it because of postoperative pain. All patients were able to comfortably complete the study at six weeks. In the study cohort, the total brake response time, reaction time, and brake time had significantly improved compared with preoperative recordings (p < 0.05). By six weeks after surgery, emergency braking time in patients undergoing a first metatarsal osteotomy is similar to that of healthy individuals.


[Application of gas chromatography in the identification of Enterobacter cloacae, Enterobacter aerogenes, and Enterobacter agglomerans].
Enterobacter cloacae, Enterobacter aerogenes and Enterobacter agglomerans were identified using gas chromatography as a substitution of the traditional techniques. Their acid methyl esters profiles were determined using a gas chromatograph Hewlett Packard 5890A and a RSL-150 heliflex capillary column. A total of 120 samples were analyzed from reference strains (ATCC 13047, 13048, 27155) and environmental isolations, eleven fatty acids were included in the profiles from which cis-9, 10-methyleneoctadecanoic acid (peak 24), cis-9-hexadecenoic acid (peak 14), octadecanoic acid (peak 23) and dodecanoic acid (peak 3), were the most important for the differentiation of the three species analyzed.


CNS involvement in overactive bladder: pathophysiology and opportunities for pharmacological intervention.
The pathophysiology of overactive bladder (OAB) syndrome is complex, and involves both peripheral and CNS factors. Several CNS disorders are associated with OAB, e.g. stroke, spinal cord injury, Parkinson's disease and multiple sclerosis, and in each disorder the pathophysiology of OAB can be multifactorial. Irrespective of cause or pathophysiology of OAB, antimuscarinic drugs are the first line of pharmacological treatment. However, adverse effects and limited efficacy makes alternative therapeutic principles desirable. Most alternative drugs used for the treatment of OAB have a peripheral site of action, mainly affecting efferent or afferent neurotransmission or the detrusor muscle itself. New targets for pharmacological intervention may be found in the CNS. Several CNS transmitters/transmitter systems are known to be involved in micturition control, but few drugs with a defined CNS site of action (e.g. baclofen, imipramine and duloxetine) have been used for the treatment of voiding disorders. GABA, glutamate, opioid, serotonin, noradrenaline (norepinephrine), and dopamine receptors and mechanisms are known to influence micturition, and drugs influencing these systems could potentially be developed for the treatment of OAB. Preclinical studies in different animal models have shown that modulation of normal micturition and detrusor overactivity by drugs acting within the spinal cord or supraspinally is possible. Promising results have been obtained in such models, e.g. with drugs interfering with GABA mechanisms, serotonin 5-HT1A receptors, mu-opioid receptors and alpha-adrenoreceptors. However, considering the limited predictability of existing animal models for efficacy in humans, positive proof of concept studies in humans are mandatory. Such studies are scarce and further investigations are needed.


Extracellular Vesicles Regulate Biofilm Formation and Yeast-to-Hypha Differentiation in Candida albicans.
In this study, we investigated the influence of fungal extracellular vesicles (EVs) during biofilm formation and morphogenesis in Candida albicans. Using crystal violet staining and scanning electron microscopy (SEM), we demonstrated that C. albicans EVs inhibited biofilm formation in vitro. By time-lapse microscopy and SEM, we showed that C. albicans EV treatment stopped filamentation and promoted pseudohyphae formation with multiple budding sites. The ability of C. albicans EVs to regulate dimorphism was further compared to EVs isolated from different C. albicans strains, Saccharomyces cerevisiae, and Histoplasma capsulatum. C. albicans EVs from distinct strains inhibited yeast-to-hyphae differentiation with morphological changes occurring in less than 4 h. EVs from S. cerevisiae and H. capsulatum modestly reduced morphogenesis, and the effect was evident after 24 h of incubation. The inhibitory activity of C. albicans EVs on phase transition was promoted by a combination of lipid compounds, which were identified by gas chromatography-tandem mass spectrometry analysis as sesquiterpenes, diterpenes, and fatty acids. Remarkably, C. albicans EVs were also able to reverse filamentation. Finally, C. albicans cells treated with C. albicans EVs for 24 h lost their capacity to penetrate agar and were avirulent when inoculated into Galleria mellonella. Our results indicate that fungal EVs can regulate yeast-to-hypha differentiation, thereby inhibiting biofilm formation and attenuating virulence. IMPORTANCE The ability to undergo morphological changes during adaptation to distinct environments is exploited by Candida albicans and has a direct impact on biofilm formation and virulence. Morphogenesis is controlled by a diversity of stimuli, including osmotic stress, pH, starvation, presence of serum, and microbial components, among others. Apart from external inducers, C. albicans also produces autoregulatory substances. Farnesol and tyrosol are examples of quorum-sensing molecules (QSM) released by C. albicans to regulate yeast-to-hypha conversion. Here, we demonstrate that fungal EVs are messengers impacting biofilm formation, morphogenesis, and virulence in C. albicans. The major players exported in C. albicans EVs included sesquiterpenes, diterpenes, and fatty acids. The understanding of how C. albicans cells communicate to regulate physiology and pathogenesis can lead to novel therapeutic tools to combat candidiasis.


Is food allergy testing reliable in pediatric atopic dermatitis? A population-based study.
We sought to assess the value and reliability of serologic testing for predicting clinical food allergy in a population-based cohort of infants with atopic dermatitis (AD). Infants 3-18 months of age, recruited from the general population, were followed quarterly for 3 years and carefully evaluated for evidence of immediate reactions to foods. Specific serum IgE levels for six foods were assayed at 3-5 years. Parents were interviewed at each visit regarding past/current immediate food-specific reactions involving skin, gut or respiratory systems. Data were entered into Excel for calculations of performance characteristics. Nine of the 40 patients (23%) who completed 3 years of follow-up had reactions to one or more foods. Reactions occurred in 5, 11 and 18% to milk, peanut and egg ingestion, respectively. In contrast, 30% of food-specific serum IgE tests were above normal. Predictive reliability of tests was generally low unless values were in the high range for peanut and milk. Conversely, egg allergy could be seen across a nearly full-spectrum of IgE values, making prediction highly unreliable. We conclude that physician and patient misinterpretation of the relevance and reliability of allergy testing may misdirect proper prevention and therapy of AD.


Development of IgE and IgG antibodies to food and inhalant allergens in children at risk of allergic disease.
In a prospective study of 92 children with at least one atopic parent, the development of the specific antibody responses to food and inhalant allergens during the first 5 years of life were assessed. By the radioallergosorbent test egg specific IgE antibody occurred in about 30% of the children with the mean peak concentration at 12 months. By the second year the prevalence of this antibody had increased whereas the mean concentration had decreased. Milk specific IgE antibody could not be shown in any subject, including four whose skin tests yielded positive results. Food specific IgG antibody was noted by antigen binding radioimmunoassays at 3 months in most children. These responses had peaked and began to fall by the fifth year. In contrast few children had detectable IgE or IgG antibody to inhalant allergens before the first 2 years of life. Both the concentration and prevalence of specific antibody, however, increased from the second to the fifth year and was greater in children whose skin tests yielded positive results. Breast feeding was associated with an increase in the prevalence of positive results from skin tests but was not associated with detectable IgE antibody to both food proteins, a lower concentration of IgG antibody to cows' milk, and was not associated with protection against the development of disease. A high level of exposure to dust mite was associated with an increased prevalence of positive results from skin tests to dust mite and appreciably higher antibody concentration. This study indicates differences in the humoral responses to food and inhalant allergens. Environmental factors appear to influence the development of these responses.


The modified bradykinesia rating scale for Parkinson's disease: reliability and comparison with kinematic measures.
Bradykinesia encompasses slowness, decreased movement amplitude, and dysrhythmia. Unified Parkinson's Disease Rating Scale-based bradykinesia-related items require that clinicians condense abnormalities in speed, amplitude, fatiguing, hesitations, and arrests into a single score. The objective of this study was to evaluate the reliability of a modified bradykinesia rating scale, which separately assesses speed, amplitude, and rhythm and its correlation with kinematic measures from motion sensors. Fifty patients with Parkinson's disease performed Unified Parkinson's Disease Rating Scale-directed finger tapping, hand grasping, and pronation-supination while wearing motion sensors. Videos were rated blindly and independently by 4 clinicians. The modified bradykinesia rating scale and Unified Parkinson's Disease Rating Scale demonstrated similar inter- and intrarater reliability. Raters placed greater weight on amplitude than on speed or rhythm when assigning a Unified Parkinson's Disease Rating Scale score. Modified bradykinesia rating scale scores for speed, amplitude, and rhythm correlated highly with quantitative kinematic variables. The modified bradykinesia rating scale separately captures bradykinesia components with interrater and intrarater reliability similar to that of the Unified Parkinson's Disease Rating Scale. Kinematic sensors can accurately quantify speed, amplitude, and rhythm to aid in the development and evaluation of novel therapies in Parkinson's disease.


Sperm count and chromatin structure in men exposed to inorganic lead: lowest adverse effect levels.
To obtain knowledge on male reproductive toxicity of inorganic lead at current European exposure levels and to establish lowest adverse effect levels, if any. A cross sectional survey of the semen of 503 men employed by 10 companies was conducted in the United Kingdom, Italy, and Belgium. The mean blood lead concentration was 31.0 microg/dl (range 4.6-64.5) in 362 workers exposed to lead and 4.4 microg/dl (range below the detection limit of 19.8) in 141 reference workers. Semen volume and sperm concentration were determined in a fresh semen sample according to an agreed protocol subject to quality assurance. The sperm chromatin structure assay (SCSA) was performed at a centralised laboratory. Extraneous determinants including centre, period of sexual abstinence, and age were taken into account in the statistical analysis. If appropriate, possible thresholds were examined by iterative threshold slope linear regression. The median sperm concentration was reduced by 49% in men with blood lead concentration above 50 microg/dl. There was no indication of a linear trend of lower sperm concentration with increasing blood lead values, but threshold slope least square regression identified a blood lead concentration of 44 microg/dl (beta=-0.037, F=4.35, p=0.038) as a likely threshold. Abnormal sperm chromatin structure was not related to blood lead concentration, but some indications of deterioration of sperm chromatin was found in men with the highest concentrations of lead within spermatozoa. Biological monitoring data did not indicate long term effects of lead on semen quantity or sperm chromatin. Adverse effects of lead on sperm concentration and susceptibility to acid induced denaturation of sperm chromatin are unlikely at blood lead concentrations below 45 microg/dl. Effects of low level exposure to lead on other measures of testicular function cannot be ruled out.


[Distribution of dipyridamole in the organism of warm-blooded animals].
Characteristics of distribution of dipyridamolum in the organism of warm-blooded animals (rats) after its intragastric introduction were studied. It was established that intact dipyridamolum in great quantity was present in visceras, blood and excrements of poisoned animals. In the greatest quantity dipyridamolum was present in excrements, tissues of stomach, small intestine, lung, spleen and kidney.


Intersystem crossing in tunneling regime: T1 → S0 relaxation in thiophosgene.
The T1 excited state relaxation in thiophosgene has attracted much attention as a relatively simple model for the intersystem crossing (ISC) transitions in polyatomic molecules. The very short (20-40 ps) T1 lifetime predicted in several theoretical studies strongly disagrees with the experimental values (∼20 ns) indicating that the kinetics of T1 → S0 ISC is not well understood. We use the nonadiabatic transition state theory (NA-TST) with the Zhu-Nakamura transition probability and the multireference perturbation theory (CASPT2) to show that the T1 → S0 ISC occurs in the quantum tunneling regime. We also introduce a new zero-point vibrational energy correction scheme that improves the accuracy of the predicted ISC rate constants at low internal energies. The predicted lifetimes of the T1 vibrational states are between one and two orders of magnitude larger than the experimental values. This overestimation is attributed to the multidimensional nature of quantum tunneling that facilitates ISC transitions along the non-minimum energy path and is not accounted for in the one-dimensional NA-TST.


Epidemiology of bovine brucellosis by a combination of rose bengal test and indirect ELISA in the five districts of Uganda.
A serological survey on bovine brucellosis was carried out 3 times between 2007 and 2009 in 3 districts (Kiboga, Mpigi and Kiruhura) in western Uganda and 2 (Kumi and Mbale) in the east employing the rose bengal test (RBT) for infected-herd screening and an indirect ELISA (iELISA) for testing the serostatus of individual animals. The animal prevalence was significantly higher in the 3 districts of the west (mean 21.5% in 2009) compared with the 2 districts (mean 3.4% in 2008) in the east (P<0.0001), though a significant difference was not observed between Kumi and Mpigi in 2008. In the west, it was the lowest in Mpigi, but a significant increase was observed between 2008 (5.3%) and 2009 (30.0%), as in Kiruhura, in which the prevalence increased from 8.1% in 2007 to 16.8% in 2009. A similar trend was also observed in Kumi, namely, the seropositivity significantly increased from 2.3% in 2007 to 6.2% in 2008 and became remarkably higher than in Mbale (0.64%). As a result, the farm prevalence was also higher in the west, especially in Kiboga in 2007 (77.8%) and 2008 (65.6%), and Mpigi in 2009 (70.8%). The linear predictor of the fitted generalized linear model proved that the logit of RBT positivity increased linearly over the increase in percent positivity values. This study demonstrated an example of an unaided self-help survey as one of the control measures in Uganda.


Dissociable neural mechanisms for determining the perceived heaviness of objects and the predicted weight of objects during lifting: an fMRI investigation of the size-weight illusion.
In size-weight (SW) illusions, people learn to scale their fingertip forces for lifting small and big objects of equal weight even though they fail to learn perceptually that both objects have the same weight. The question then arises as to what the separate neural mechanisms are for determining the perceived heaviness of objects and the predicted weight of these objects during lifting. To answer this question, we used fMRI to first identify areas that code for the size, weight, and density of objects using an adaptation paradigm. We then contrasted BOLD in the SW illusion condition in which subjects falsely perceived the smaller of two equally weighted objects as heavier versus a condition in which size and weight did not differ between objects. Sensory areas in the parietal and temporal cortex adapted to the size of objects and the primary motor area (M1) contralateral to the lifting hand adapted to the weight of objects. The ventral premotor area (PMv), which did not adapt to either the size or the weight of objects, adapted instead to the density of objects, and responded more when subjects falsely perceived differences in weight between objects in the SW illusion condition. Taken together, we conclude that the real-world properties of objects, such as size and weight, are computed by sensory areas and by M1 respectively, whereas the perceived heaviness of objects, presumably based on their apparent density, is computed by PMv, a higher-order area well placed to integrate sensory information about the size of objects and the weight of objects.


The effect of motion correction on pharmacokinetic parameter estimation in dynamic-contrast-enhanced MRI.
A dynamic-contrast-enhanced magnetic resonance imaging (DCE-MRI) dataset consists of many imaging frames, often acquired both before and after contrast injection. Due to the length of time spent acquiring images, patient motion is likely and image re-alignment or registration is required before further analysis such as pharmacokinetic model fitting. Non-rigid image registration procedures may be used to correct motion artefacts; however, a careful choice of registration strategy is required to reduce misregistration artefacts associated with enhancing features. This work investigates the effect of registration on the results of model-fitting algorithms for 52 DCE-MR mammography cases for 14 patients. Results are divided into two sections: a comparison of registration strategies in which a DCE-MRI-specific algorithm is preferred in 50% of cases, followed by an investigation of parameter changes with known applied deformations, inspecting the effect of magnitude and timing of motion artefacts. Increased motion magnitude correlates with increased model-fit residual and is seen to have a strong influence on the visibility of strongly enhancing features. Motion artefacts in images close to the contrast agent arrival have a disproportionate effect on discrepancies in parameter estimation. The choice of algorithm, magnitude of motion and timing of the motion are each shown to influence estimated pharmacokinetic parameters even when motion magnitude is small.


Determination of groundwater quality index of a highland village of Kerala (India) using Geographical Information System.
In this study, the authors' goal was to understand the groundwater quality of Nedumkandam panchayat by an integrated approach of traditional water quality analysis and Geographical Information Systems (GIS). Fourteen wells were identified from the study area and samples were collected and analyzed using standard protocols (American Public Health Association, 1998). Parameters analyzed include pH, hardness, nitrate, chloride, sulfate, phosphate, trace metals (cadmium, zinc, copper, and lead), and fecal coliforms. All parameters except pH, cadmium, and fecal coliforms were within the limit of drinking water quality standards prescribed by the Bureau of Indian Standards (BIS) (BIS, 1983). The spatial distribution of physico-chemical and biological parameters was analyzed using the Inverse Distance Weighted (IDW) approach and the maps thus obtained were integrated using the raster calculator option of spatial analyst in ArcGIS 8.3 software, and a water quality index (WQI) was calculated. Based on the WQI values, the study area was divided into poor, moderate, and good water quality zones.


The effect of experience and gender on cardiovascular and metabolic responses with dynamic Tae Kwon Do exercise.
This study, conducted at the Exercise Physiology Laboratory of Auburn University, AL, addressed and compared the acute cardiovascular and metabolic effects elicited by novice and experienced men and women participants during a single bout of dynamic Tae Kwon Do exercise and investigated whether or not dynamic Tae Kwon Do practice is an exercise modality that provides sufficient cardiorespiratory demand for enhancing aerobic fitness and promoting weight and fat loss. Twenty-eight men and women (aged 19-42) were assigned to 1 of the following 4 groups: Tae Kwon Do experienced and trained men (ME), Tae Kwon Do experienced and trained women (FE), novice Tae Kwon Do men (MN), and novice Tae Kwon Do women (FN). The results of this investigation indicate that this form of exercise can be performed for an extended period of 20 minutes. All 4 groups achieved the recommended stimulus for effective initiation of cardiovascular adaptations and conditioning. The mean exercise heart rate responses (88.3-92.2% of maximal heart rate [HR max]) were similar for all groups. The observed exercise intensity ranged from 67.9 to 72.1% VO2max, and no significant difference based on the experience and gender and exercise oxygen uptake could be established. Data in this study indicate a high caloric expenditure for this mode of exercise. Total caloric cost of 20 minutes of dynamic Tae Kwon Do, 194.8 and 201.6 kcal for novice women and experienced women, respectively, was significantly lower in comparison with that of their men counterparts (316.5 and 286.5 kcal, respectively), but no significant relationship between experience and energy cost was found. The conclusion of this study indicates that dynamic Tae Kwon Do is an exercise modality that can be appropriately prescribed for cardiovascular conditioning, weight control, and fat loss.


Electroacupuncture Ameliorates Depressive-Like State and Synaptic Deficits Induced by Hyper-Cholinergic Tone During Chronic Stress in Rats.
BACKGROUND Major depressive disorder (MDD) is the leading cause of disability around the world. It is generally agreed that the central cholinergic system plays an important role in emotional regulation. Acetylcholine (ACh) is now a new target for antidepressants. Therefore, the aim of this study was to evaluate the effect of acupuncture on depressive behaviors, cholinergic tones, and synaptic plasticity in the prefrontal cortex (PFC) in chronic unpredictable mild stress (CUMS). MATERIAL AND METHODS We randomly divided 36 male Sprague-Dawley (SD) rats into the Normal group, Stress group, Physostigmine+stress (Phys+stress) group, and Electroacupuncture+physostigmine+stress (EA+Phys+stress) group. Rats underwent CUMS exposure for 42 days. After 28 days of CUMS, rats received physostigmine or EA treatment for 2 weeks. Rats in the Phys+stress and EA+Phys+stress group received an intraperitoneal injection of physostigmine (TOCRIS, UK, 5 mg/kg) daily. Rats in the EA+Phys+stress group also received EA stimulation at GV 20 (Baihui), GV 29 (Yintang), LI 4 (Hegu), and LR 3 (Taichong) daily for 2 weeks. RESULTS We found that EA ameliorated weight loss and the depressive-like behaviors in the sucrose preference test, novelty-suppressed feeding test, and open-field test. There was significantly decreased expression of ACh and increased expression of acetylcholinesterase (AChE) after EA treatment. Consistent with the behavior tests and cholinergic tones, there were increased spine density and expressions of synaptic proteins, including brain-derived neurotrophic factor (BDNF), glutamate receptor 1 (GluR1), glutamate receptor 2 (GluR2), postsynaptic density protein 95 (PSD95), and synapsin I in the PFC. CONCLUSIONS The results suggest that EA can reverse the depressive-like behaviors and synaptic deficits induced by hyper-cholinergic tone during chronic stress via the modulation of hyper-cholinergic tone.