Prognostic Significance of Thyroglobulin Antibodies in Differentiated Thyroid Cancer.
To investigate whether variations in thyroglobulin autoantibodies (TgAb) are related to the recurrence or persistence of differentiated thyroid carcinoma (DTC) and may therefore be useful as surrogate tumor markers. Design and Methods. We retrospectively studied 98 subjects (83 women, 47 ± 15 years old) from an initial cohort of 1017 patients treated for DTC in five hospitals, with positive TgAb at any time during the follow-up. Patients presented five different patterns of evolution of serum TgAb concentrations: (1) stable positive TgAb, (2) de novo appearance, (3) an increase of more than 50%, (4) TgAb levels from positive to negative, and (5) a decrease of more than 50%. In the group of 11 patients with stable TgAb, four cases presented persistence of the disease with structural incomplete response. In the group of 22 patients with sustained increasing trend rising more than 50% or de novo detectable TgAb levels, three patients were diagnosed with structural incomplete response. There was no evidence of recurrence or persistence of the disease in any of the 65 patients who showed a significant decrease in (n = 35) or disappearance of (n = 30) TgAb. Our results suggest that not only the appearance of a significant increase in TgAb but also stable concentrations of TgAb should be regarded as a sufficient risk condition for an active search for recurrent or persistent disease. Conversely, a significant decrease in TgAb levels can represent a good prognostic sign.


Regulatory T cells in the treatment of disease.
Regulatory T (Treg) cells suppress inflammation and regulate immune system activity. In patients with systemic or organ-specific autoimmune diseases or those receiving transplanted organs, Treg cells are compromised. Approaches to strengthen Treg cell function, either by expanding them ex vivo and reinfusing them or by increasing the number or capacity of existing Treg cells, have entered clinical trials. Unlike the situation in autoimmunity, in patients with cancer, Treg cells limit the antitumour immune response and promote angiogenesis and tumour growth. Their immunosuppressive function may, in part, explain the failure of many immunotherapies in cancer. Strategies to reduce the function and/or number of Treg cells specifically in tumour sites are being investigated to promote antitumour immunity and regression. Here, we describe the current progress in modulating Treg cells in autoimmune disorders, transplantation and cancer.


Positive Chemotaxis of the Entomopathogenic Nematode Steinernema australe (Panagrolaimorpha: Steinenematidae) towards High-Bush Blueberry (Vaccinium corymbosum) Root Volatiles.
The foraging behavior of the infective juveniles (IJs) of entomopathogenic nematodes (EPNs) relies on host-derived compounds, but in a tri-trophic context, herbivore-induced root volatiles act as signals enhancing the biological control of insect pests by recruiting EPNs. In southern Chile, the EPN Steinernema australe exhibits the potential to control the raspberry weevil, Aegorhinus superciliosus, a key pest of blueberry Vaccinium corymbosum. However, there is no information on the quality of the blueberry root volatile plume or the S. australe response to these chemicals as putative attractants. Here, we describe the root volatile profile of blueberries and the chemotaxis behavior of S. australe towards the volatiles identified from Vaccinium corymbosum roots, infested or uninfested with A. superciliosus larvae. Among others, we found linalool, α-terpineol, limonene, eucalyptol, 2-carene, 1-nonine, 10-undecyn-1-ol, and methyl salicylate in root volatiles and, depending on the level of the emissions, they were selected for bioassays. In the dose-response tests, S. australe was attracted to all five tested concentrations of methyl salicylate, 1-nonine, α-terpineol, and 2-carene, as well as to 100 µg mL-1 of 10-undecyn-1-ol, 0.1 and 100 µg mL-1 of linalool, and 100 µg mL-1 of limonene, whereas eucalyptol elicited no attraction or repellency. These results suggest that some volatiles released from damaged roots attract S. australe and may have implications for the biocontrol of subterranean pests.


Effects of diet supplementation with Camu-camu (Myrciaria dubia HBK McVaugh) fruit in a rat model of diet-induced obesity.
Amazonian Camu-camu fruit (Myrciaria dubia HBK Mc Vaugh) has attracted interest from food and cosmetics industries because of its rich content of vitamin C, flavonoids and anthocyanins. The goal of this study was investigates the antiobesity action of the ingestion of the Camu-camu pulp in a rat model of diet-induced obesity. Wistar rats with obesity induced by subcutaneous injection of monosodium glutamate receiving diet ad libitum. The rats were divided in two groups: an experimental group that ingested 25 mL/day of Camu-camu pulp (CCG) and a non treated group (CG). After 12 weeks, the animals were sacrificed. Blood, liver, heart, white adipose tissues were collected and weighted, biochemical and inflammatory profiles were determinate as well. Animals that received the pulp of Camu-camu reduced their weights of the fat in white adipose tissues, glucose, total cholesterol, triglycerides, LDL-c and insulin blood levels. There was an increase in HDL-c levels. No change was observed in inflammatory markers and liver enzymes. Camu-camu pulp was able to improve the biochemical profile of obesity in rats suggesting that this Amazonian fruit can be further used such a functional food ingredient in control of chronic diseases linked to obesity.


Perfect light trapping in nanoscale thickness semiconductor films with a resonant back reflector and spectrum-splitting structures.
The optical absorption of nanoscale thickness semiconductor films on top of light-trapping structures based on optical interference effects combined with spectrum-splitting structures is theoretically investigated. Nearly perfect absorption over a broad spectrum range can be achieved in <100 nm thick films on top of a one-dimensional photonic crystal or metal films. This phenomenon can be attributed to interference induced photonic localization, which enhances the absorption and reduces the reflection of the films. Perfect solar absorption and low carrier thermalization loss can be achieved when the light-trapping structures with a wedge-shaped spacer layer or semiconductor films are combined with spectrum-splitting structures.


Spirometry for the primary care provider.
Spirometry is used in conjunction with a patient's history and physical examination to help evaluate lung function and assist in diagnosing or monitoring different categories of lung disease. This article reviews the fundamentals of spirometry, including patient education and interpreting results.


Effect of high-flow nasal cannula oxygen therapy in patients with chronic obstructive pulmonary disease: A meta-analysis.
High-flow nasal cannula oxygen therapy reduces the arterial partial pressure of carbon dioxide and acute exacerbation but does not increase exercise capacity or decrease hospitalisation or mortality. The study aimed to test the hypothesis that in chronic obstructive pulmonary disease patients, the use of high-flow nasal cannula decreases arterial partial pressure of carbon dioxide and increases the partial pressure of oxygen and 6-min walking distance. PubMed, Embase and the Cochrane library were searched for eligible studies published from database inception to November 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist). The primary outcomes were partial pressure of carbon dioxide and partial pressure of oxygen, and the secondary outcomes were transcutaneous partial pressure of carbon dioxide and 6-min walking distance. Nine studies (680 patients) were included. high-flow nasal cannula did not decrease partial pressure of carbon dioxide compared with the control interventions (mean difference = -0.81, 95% confidence interval: -2.68 to 1.06, p = .395; I2 = 42.9%, pheterogeneity = .105). high-flow nasal cannula decreased partial pressure of carbon dioxide compared with long-term oxygen therapy (mean difference = -3.25, 95% confidence interval: -5.65 to -0.85, p = .008; I2 = 0%, pheterogeneity = .375); no difference was observed for the control modalities. high-flow nasal cannula resulted in better partial pressure of carbon dioxide compared with control interventions in hypoxemic patients (mean difference = -2.59, 95% confidence interval: -4.82 to -0.35, p = .023; I2 = 32.5%, pheterogeneity = .224), but not in other types of patients. high-flow nasal cannula did not increase partial pressure of oxygen compared with the control interventions (mean difference = 1.17, 95% confidence interval: -1.50 to 3.83, p = .390; I2 = 0%, pheterogeneity = .660). high-flow nasal cannula decreased transcutaneous carbon dioxide tension (transcutaneous partial pressure of carbon dioxide) compared with the control interventions (mean difference = 2.37, 95% confidence interval: 0.07-4.68, p = .044; I2 = 8.7%, pheterogeneity = .295). high-flow nasal cannula increased 6-min walking distance compared with the control interventions (mean difference = 18.22, 95% confidence interval: 0.86-,35.57, p = .040; I2 = 0%, pheterogeneity = .918). The sensitivity analyses showed that the results were robust. High-flow nasal cannula did not significantly decrease partial pressure of carbon dioxide or increase partial pressure of oxygen in chronic obstructive pulmonary disease patients, which is different from the previous meta-analysis, but it decreases transcutaneous partial pressure of carbon dioxide and increased 6-min walking distance. This meta-analysis shows that in patients with chronic obstructive pulmonary disease, high-flow nasal cannula improves both transcutaneous partial pressure of carbon dioxide and 6-min walking distance, suggesting the high-flow nasal cannula has benefits in the management of chronic obstructive pulmonary disease. Considering that the literature suggests no impact of high-flow nasal cannula on hospitalisation and mortality, the benefits of high-flow nasal cannula might be limited to the patients who survive the chronic obstructive pulmonary disease events. Still, the global impact of high-flow nasal cannula on the quality of life of patients with chronic obstructive pulmonary disease should be examined.


Upper gastrointestinal tract malignant obstruction: initial results of palliation with a flexible covered stent.
The authors treated 21 patients with inoperable upper gastrointestinal tract malignant obstruction from the esophagus to the duodenum by means of intubation with a flexible covered stent with fluoroscopic guidance. Stent placement was successful and relief of dysphagia was immediate in 18 (86%) patients, without serious complication. The average dysphagia score decreased from 2.6 (dysphagia to liquids) to 1.0 (dysphagia to normal solid food). Placement of a flexible covered stent provides easy, safe, and effective palliation of upper gastrointestinal malignant obstruction.


[Bone marrow aplasia and gold salts. Review of the literature apropos of 2 cases].
Bone marrow aplasia remains the most serious adverse effect with gold therapy. Its prevalence is still a controversial issue and at present it is not possible to give accurate figures on its frequency. Two patients diagnosed of rheumatoid arthritis are reported. They underwent chrysotherapy and developed bone marrow aplasia within a 2-month period of therapy. The pathogenic mechanism of blood dyscrasias secondary to gold salts is still unknown. The best available method in the prevention of this serious condition is the periodical obtention of complete blood counts.


[Changes of cytokine levels in ascitic fluid after intraperitoneal administration of OK-432 or CDDP].
In order to evaluate the biological response after intraperitoneal administration of OK-432 and CDDP, we studied the changes of cytokine levels in ascitic fluid. A total of 53 gastric cancer patients were included in this study. OK-432 20KE was administered in 7 patients and CDDP was administered in 4 patients intraperitoneally during operation. The IL-6, IL-8, TNF-alpha and sTNF RI levels in ascitic fluid were measured from 0 to 5 postoperative day. These results were compared with those obtained from the control groups (42 patients). The ascitic level of IL-6 increased immediately after operation, then gradually decreased. The elevations of IL-6 from 0 to 5 postoperative day were remarkably higher in the OK-432 treated group, and those on 0 and 1 postoperative days were remarkably lower in CDDP treated group than in the control group. Similarly, the ascitic level of IL-8 elevated soon after operation and then decreased gradually. In the OK-432 treated group, the ascitic level of IL-8 was significantly higher than in the control group from 0 to 2 postoperative day. Ascitic TNF-alpha was detectable only in the ascites soon after operation in the OK-432 treated group. The ascitic level of sTNF RI peaked on 2 postoperative day in the control and the OK-432 treated group and 1 postoperative day in the CDDP treated group. There were no significant differences between these groups.


Ultrastructural localization and function of dopamine D1-like receptors in the substantia nigra pars reticulata and the internal segment of the globus pallidus of parkinsonian monkeys.
The motor symptoms of Parkinson's disease (PD) are commonly attributed to striatal dopamine loss, but reduced dopamine innervation of basal ganglia output nuclei, the internal globus pallidus (GPi) and the substantia nigra pars reticulata (SNr) may also contribute to symptoms and signs of PD. Both structures express dopamine D1 and D5 receptors under normal conditions, and we have recently demonstrated that their local activation reduces neuronal discharge rates and enhances bursts and oscillatory activity in both nuclei of normal monkeys [M.A. Kliem et al. (2007)J. Neurophysiol., 89, 1489-1500]. Here, we determined the ultrastructural localization and function of D1-like receptors in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated parkinsonian monkeys. In both normal and MPTP-treated monkeys, most of the D1 and D5 receptor immunoreactivity was associated with unmyelinated axons, but we also found significant postsynaptic D5 receptor immunostaining in dendrites of GPi and SNr neurons. A significant proportion of axonal D1 immunostaining was bound to the plasma membrane in both normal and MPTP-treated monkeys. Local microinjections of the D1/D5 receptor agonist SKF82958 significantly reduced discharge rates in GPi and SNr neurons, while they increased burst firing and oscillatory activity in the 3-15-Hz band in SNr, but not in GPi, of parkinsonian monkeys. Together with our recent findings from normal monkeys, these data provide evidence that functional D1/D5 receptors are expressed in GPi and SNr in both normal and parkinsonian states, and that their activation by endogenous dopamine (under normal conditions) or dopamine receptor agonists (in parkinsonism) may regulate basal ganglia outflow.


[Five-year experience with ileal neobladder according to original and modified Hautmann method].
Radical cystectomy is the method of treatment of muscle invasive tumor of the urinary bladder, T2-T4a, N0-Nx, M0, which is also performed in patients at high risk of superficial tumors G3, CIS (carcinoma in situ), which are resistant to BCG and diffuse papillary tumors which can not be controlled by conservative treatment. After radical cystectomy, an adequate derivation of the urine is needed, and in the best interest for patient's comfort, is to make a new bladder from the parts of gastrointestinal tract and suture it to the rest of the urethra. In 1988, German surgeon Richard Hautmann published his method of creating a new bladder, for what he used 60cm of ileum. This method is in use at Department of Urology, Military Medical Academy, Belgrade, but, we introduced our modification of original operation because of early and late postoperative complications. The analysis of early and late complications after derivative surgery of orthotopic ileal bladder according to Hautmann. The patients operated according to original and modified method were analyzed. From 2000-2004, 117 radical cystectomies were performed due to malignant urinary bladder tumors as well as the same number of derivative surgeries at the Clinic for Urology, Military Medical Academy, Belgrade. During this five-year period, the orthotopic ileal neobladder surgery according to Hautmann was performed in 41 patients after radical cystectomy. Twenty three patients were operated on using the original method and 18 patients by our modification. Metabolic disorders and problems of high capacity of neobladder were manifested in all patients operated on by original method, while the stenosis of the ureteroileal anastomosis was present in most of these patients. Metabolic disorders were less frequent and of lower degree in patients operated by our modification and there was no stenosis of the ureteroileal anastomosis. The problems with urination were not reported. In our opinion and on the basis of our experience, Hautmann method is the method with fewer complications. However, our modifications are also acceptable because the number of complications is smaller and the value of operation is being kept.


Different nanocellulose morphologies (cellulose nanofibers, nanocrystals and nanospheres) extracted from Sunn hemp (Crotalaria Juncea).
Nanocellulose of different morphologies was extracted from Sunn Hemp (Crotalaria Juncea) using acid hydrolysis. The work focused on two objectives: first, to valorize the Sunn Hemp fibers for nanocellulose (NC) production, and second, to study the effects of acid concentration on different morphologies of NC and their properties. The study extracted nanocellulose at five different concentrations of H2SO4: 16 %, 32 %, 48 %, 64 %, and 72 %. Obtained nanocellulose was characterized by Scanning Electron Microscopy (FE-SEM), Atomic Force Microscopy (AFM), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD) and Thermogravimetric Analysis (TGA). AFM and FE-SEM confirmed the production of three different morphologies of nanocellulose. The NC-32 had a web-like structure typically observed for cellulose nanofibrils (CNF), whereas NC-48 and NC-64 were observed as cellulose nanocrystals (CNC) with rod-like and needle-like shapes, respectively, and NC-72 displayed spherical particles termed cellulose nanospheres (CNS). The total crystallinity index of NC was calculated using FTIR, and a similar trend of crystallinity was also observed from XRD analysis. NC-32 was obtained with the highest yield of 94.83 %, followed by 91.40 % and 81.70 % for NC-48 and NC-64, respectively, whereas NC-72 yielded the lowest yield of 12.03 %. NC-72 had the highest thermal stability among other NC morphologies.


Effect of reinforcement on facial responsivity and persistence in children with attention-deficit hyperactivity disorder.
Children with Attention Deficit-Hyperactivity Disorder (ADHD) may learn poorly under conditions of inconsistent (partial) reinforcement because they are easily frustrated and fail to develop persistence. To test this hypothesis, a nonsense word spelling task was used with 22 ADHD and 20 control children to investigate the effects of partial and continuous reinforcement on facial responsivity (frustration measure), words spelled correctly (learning performance measure), and persistence ratings. Partially reinforced ADHD children manifested higher levels of frustration in both acquisition and extinction than any other group and gave significantly lower persistence ratings across acquisition than partially reinforced control children. ADHD children spelled fewer words correctly than controls, regardless of reinforcement schedule. These findings suggest that partial reinforcement training develops persistence in normal but not ADHD children. The findings have theoretical implications for the etiology of ADHD as well as practical implications for designing behavior modification programs to treat ADHD.


(1S*,4'S*,5R*)-1-Isopropyl-5-meth-oxy-2',3-dimethyl-4,6-dioxa-2-aza-spiro-[bicyclo-[3.2.0]hept-2-ene-7,4'-isoquinoline]-1',3'(2'H,4'H)-dione.
In the isoquinoline ring system of the title mol-ecule, C(18)H(20)N(2)O(5), the N-heterocyclic ring is in a half-boat conformation. The dioxa-2-aza-spiro ring is essentially planar, with a maximum deviation of 0.029 (1) Å, and makes a dihedral angle of 30.63 (5)° with the benzene ring. The mol-ecular structure is stabilized by a weak intra-molecular C-H⋯O hydrogen bond, which generates a S(6) ring motif. In the crystal, mol-ecules are linked via weak inter-molecular C-H⋯O hydrogen bonds into a three-dimensional supra-molecular network. Additional stabilization is provided by π-π stacking inter-actions between symmetry-related benzene rings with a centroid-centroid distance of 3.6507 (5) Å.


Chemotherapy cardiotoxicity: cardioprotective drugs and early identification of cardiac dysfunction.
Chemotherapy cardiotoxicity is an emerging problem and it is very important to prevent cardiac dysfunction caused by anticancer drugs. The aim of this study was to assess the alterations of the cardiac function induced by chemotherapy in a follow-up of 2 years and to evaluate the cardioprotective role of angiotensin-converting enzyme inhibitors (ACEIs) in the prevention of cardiac dysfunction. A prospective study was carried out using patients with breast cancer (85 women; median age 57 ± 12 years) and other inclusion and exclusion criteria. On the basis of treatment, patients were divided into six groups: fluorouracil-epirubicincyclophosphamide, FEC (group A); FEC and trastuzumab (B); trastuzumab (C); FEC and taxotere (D); FEC, paclitaxel and trastuzumab (E); and chemotherapy and cardioprotective drugs (F). Cardiological evaluation including electrocardiogram and conventional echocardiogram with tissue Doppler imaging (TDI) was carried out at T0 (before starting chemotherapy), T1 (after 6 months from the start of chemotherapy) and T2 (2 years after the end of chemotherapy). Significant changes in the TDI parameters of systolic and diastolic function were observed at T1 and T2 in all patients. A significant reduction of left ventricular ejection fraction (LVEF) was observed only at T2. In the patients treated with ACEI (F), these changes were less significant than in other groups and they do not have significant changes in the indices of diastolic function. TDI is more sensitive than conventional echocardiogram in the early diagnosis of cardiac dysfunction and ACEIs seem to have an important role in the prevention of cardiotoxicity.


Monitoring the kinetics of reactions between natural organic matter and Al(III) ions using differential absorbance spectra.
This study examined the kinetics of the binding of Al(III) ions by natural organic matter (NOM) exemplified by Suwannee River humic acid (SRHA). This processes was studied for a 5-8 pH range and environmentally relevant concentrations of the system components. Al(III)-NOM interactions were quantified using differential absorbance spectra whose intensity and shape depended on pH and reaction time. In all cases the differential spectra had four bands with maxima located at 245, 275, 320, 380 nm. These bands were assigned to the engagement of the carboxylic-like and/or phenolic-like groups, as well as electrostatic gel in NOM. Several parameters of the absorbance spectra (e.g., spectral slopes of log-transformed spectra in wavelength range 260-270 and 350-400 nm, ΔS260-270 and ΔS350-400 respectively) were linearly correlated (R2 = 0.98) with concentrations of carboxylic-like groups and total NOM-bound Al(III) ions predicted based on the NICA-Donnan model. The binding of Al(III) ion by NOM at all pHs was modeled assuming the presence of three kinetically distinct sites. This study demonstrates that differential absorbance spectroscopy can be used to quantify the kinetics and mechanisms of NOM-metal ions interactions and monitor them in practically important system including water treatment operations.


Intertwined arbovirus transmission activity: reassessing the transmission cycle paradigm.
Arboviruses are emerging/reemerging infectious agents worldwide. The factors within this scenario include vector and host population fluctuations, climatic changes, anthropogenic activities that disturb ecosystems, an increase in international flights, human mobility, and genetic mutations that allow spill-over phenomenon. Arboviruses are maintained by biologic transmission among vectors and hosts. Sometimes this biological transmission is specific and includes one vector and host species such as Chikungunya (CHIKV), Dengue (DENV), and urban Yellow Fever (YFV). However, most of the arboviruses are generalist and they use many vectors and hosts species. From this perspective, arboviruses are maintained through a transmission network rather than a transmission cycle. This allows us to understand the complexity and dynamics of the transmission and maintenance of arboviruses in the ecosystems. The old perspective that arboviruses are maintained in close and stable transmission cycles should be modified by a new more integrative and dynamic idea, representing the real scenario where biological interactions have a much broader representation, indicating the constant adaptability of the biological entities.


Improved spontaneous erectile function in men with mild-to-moderate arteriogenic erectile dysfunction treated with a nightly dose of sildenafil for one year: a randomized trial.
To test the hypothesis that sildenafil (50 mg nightly for one year) can improve spontaneous erectile function (EF) in men with mild-to-moderate arteriogenic erectile dysfunction (ED) responsive to erectogenic treatment. In a prospective open-label trial, 112 men with ED were randomized to sildenafil 50 mg nightly or sildenafil 50 or 100 mg as needed for 12 months, followed by one-month and 6-month non-medicated periods. Non-randomized, non-medicated men with ED were also assessed. The EF domain of the International Index of Erectile Function (IIEF EF) and the peak systolic velocity (PSV) of penile cavernous arteries were used to measure the efficacy. After sildenafil treatment and a subsequent non-medicated month, IIEF EF was normal in 29 of 48 (60.4%, 95% confidence interval [CI]: 45.3-74.2%) of the nightly group vs. 4 of 49 (8.2%, 95% CI: 2.3-19.6%) of the as-needed group. PSV improved by 11.2 cm/s (95% CI: 4.7-21.4; P=0.012) in the nightly group but only by 3.4 cm/s (-5.1-14.7; P=0.435) in the as-needed group. IIEF EF normalized in 1 of 18 (5.6%, 95% CI: 0.1-27.3%) non-medicated men and the PSV declined slightly. Six months after treatment, the IIEF EF remained normal and PSV was stabilized in most (28/29, 97%) nightly group men who had initially normalized. Sildenafil nightly for one year resulted in ED regression that persisted well beyond the end of treatment, so that spontaneous EF was characterized as normal on the IIEF in most men. The results from this open-label, randomized trial warrant verification under double-blind, placebo-controlled conditions.


Merkel Cell Carcinoma of the Trunk: Two Case Reports and Imaging Review.
Merkel cell carcinoma (MCC) is a rare malignant cutaneous tumor primarily located in the head and neck. We report the imaging features of pathologically confirmed MCC in the trunk. On US, MCC showed heterogeneous echogenicity with perpendicular hypoechoic linear bands that resembled "columns of smoke" in the skin and subcutaneous layers as well as prominent vascularity. On MRI, the tumor showed hypointensity on T1-weighted images and hyperintensity on proton density and T2-weighted images with linear low-signal bands in the skin and subcutaneous layers as well as intense enhancement on T1-enhanced images. Although MCC has nonspecific imaging features, these characteristics may be helpful for the early diagnosis of this disease.


Autosomal recessive primary microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings.
Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder. It is characterized by two principal features, microcephaly present at birth and nonprogressive mental retardation. The microcephaly is the consequence of a small but architecturally normal brain, and it is the cerebral cortex that shows the greatest size reduction. There are at least seven MCPH loci, and four of the genes have been identified: MCPH1, encoding Microcephalin; MCPH3, encoding CDK5RAP2; MCPH5, encoding ASPM; and MCPH6, encoding CENPJ. These findings are starting to have an impact on the clinical management of families affected with MCPH. Present data suggest that MCPH is the consequence of deficient neurogenesis within the neurogenic epithelium. Evolutionary interest in MCPH has been sparked by the suggestion that changes in the MCPH genes might also be responsible for the increase in brain size during human evolution. Indeed, evolutionary analyses of Microcephalin and ASPM reveal evidence for positive selection during human and great ape evolution. So an understanding of this rare genetic disorder may offer us significant insights into neurogenic mitosis and the evolution of the most striking differences between us and our closest living relatives: brain size and cognitive ability.


Identification of oxidative stress-induced gene expression profiles in cavernosal endothelial cells.
The aim of the present study was to explore the regulation status of genes in oxidative stress (OS)‑induced endothelial dysfunction and to elucidate the mechanism of action of OS‑associated genes, which induce cavernosal endothelial dysfunction in erectile dysfunction (ED). OS was established in purified cavernosal endothelial cells (CECs) using xanthine/xanthine oxidase and the differentially expressed OS‑associated genes were analyzed using gene microarrays. In addition, an ED rat model was established through bilateral internal iliac artery ligation with hyperlipidemia and was verified by an intracavernosal pressure test. The selected OS‑associated genes were validated in the CECs and ED rat model using reverse transcription‑quantitative polymerase chain reaction. Student's t‑test and one‑way analysis of variance were performed using SBC analysis system. Gene microarray analysis revealed that 13090 (31.92%) genes were expressed in the control group, whereas 12039 (29.35%) genes were expressed in the treated group. The cut‑off value for differential expression was set at 2.0 fold‑change and 2480 genes were found to be differentially expressed compared with the control group. Of these cells, 1454 were upregulated and 1026 were downregulated. Cluster analysis identified relevant cell signaling pathways that were hypothesized to be significant in OS‑associated endothelial dysfunction, including the cytokine‑cytokine receptor interactions, nitrogen metabolism, coagulation cascades and cell adherens. Cxcl12, Tgfbr1, Asns, Bdkrb1 and Cdh3 genes showed a corresponding variation in the CECs and ED rat model compared with the results of the gene microarray analysis. In conclusion, in the present study, the network of differentially expressed genes and OS‑associated signaling pathways identified using gene microarray analysis were validated in the CECs and ED rat model. The results indicated that OS may lead to endothelial dysfunction through certain cell signaling pathways, inducing ED. However, further functional verification is required in order to elucidate the underlying mechanisms of OS‑associated cell signaling pathways in ED.


Escape statistics for parameter sweeps through bifurcations.
We consider the dynamics of systems undergoing parameter sweeps through bifurcation points in the presence of noise. Of interest here are local codimension-one bifurcations that result in large excursions away from an operating point that is transitioning from stable to unstable during the sweep, since information about these "escape events" can be used for system identification, sensing, and other applications. The analysis is based on stochastic normal forms for the dynamic saddle-node and subcritical pitchfork bifurcations with a time-varying bifurcation parameter and additive noise. The results include formulation and numerical solution for the distribution of escape events in the general case and analytical approximations for delayed bifurcations for which escape occurs well beyond the corresponding quasistatic bifurcation points. These bifurcations result in amplitude jumps encountered during parameter sweeps and are particularly relevant to nano- and microelectromechanical systems, for which noise can play a significant role.


[Vascularization of the choroid tela of the 4th ventricle in sheep (Ovis aries)].
The tela choroïdea of the fourth ventricle of the sheep is vascularized principally by the caudal cerebellar artery and the dorsal network of the medulla. The choroidal branches arising from these arteries supply the capillary network of the choroïd plexus. The latter drains towards the sigmoid sinus either through the dorsal veins of the medulla or by an anastomose with the ventral veins. The latter are arched and seem to be metameric. Some choroid veins are tributary of the hemispheric cerebellar veins.


The genetic versus pharmacological invalidation of the cannabinoid CB(1) receptor results in differential effects on 'non-associative' memory and forebrain monoamine concentrations in mice.
The endocannabinoid CB(1) receptor has been implicated in the inhibitory control of learning and memory. In the present experiment, we compared the behavioral response of CB(1) receptor knockout mice (CB(1)R(-/-)) with animals administered CB(1) receptor antagonist/inverse agonist SR141716A (rimonabant; 3 mg/kg IP, 30 min pre-trial) in terms of acquisition and retention of a habituation task and changes in cerebral monoamines. The results can be summarized as follows: (i) the acute and chronic invalidation of the CB(1) receptor resulted in an increase of behavioral habituation during the first exposure to an open field, indicative of enhanced acquisition of the task; (ii) CB(1)R(-/-) mice, but not rimonabant-treated animals, showed enhanced retention of the habituation task when re-tested 48 h and 1 week subsequent to the first exposure to the open field, respectively; (iii) the facilitation of retention of the habituation task in CB(1)R(-/-) mice was accompanied by a selective and site-specific increase in serotonin activity in hippocampus; and (iv) rimonabant-treated animals displayed 'antidepressant-like' neurochemical alterations of cerebral monoamines, that is, most parameters of monoaminergic activity were increased especially in dorsal striatum and hippocampus. Taken together, the present findings demonstrate that the genetic disruption of the CB(1) receptor gene can cause an improvement of behavioral habituation, which is considered to represent a form of 'non-associative' learning. Furthermore, our data support the assumption of a rimonabant-sensitive cannabinoid receptive site that is different from the 'classical' CB(1) receptor and which, under physiological conditions, might be involved in the inhibitory control of the acquisition but not retention of non-associative learning tasks.


Non-obstructive azoospermia and maturation arrest with complex translocation 46,XY t(9;13;14)(p22;q21.2;p13) is consistent with the Luciani-Guo hypothesis of latent aberrant autosomal regions and infertility.
To describe clinical and histological features observed in the setting of an unusual complex translocation involving three autosomes (9, 13, and 14) identified in an otherwise healthy male referred for infertility consultation. The patient was age 30 and no family history was available (adopted). Total azoospermia was confirmed on multiple semen analyses. Peripheral karyotype showed a 46,XY t(9;13;14)(p22:q21.2;p13) genotype; no Y-chromosome microdeletions were identified. Cystic fibrosis screening was negative. Bilateral testis biopsy revealed uniform maturation arrest and peritubular fibrosis. Formal genetic counseling was obtained and the extant literature reviewed with the couple. Given the low probability of obtaining sperm on testicular biopsy, as well as the high risk of any retrieved sperm having an unbalanced genetic rearrangement, the couple elected to proceed with fertility treatment using anonymous donor sperm for insemination. Although genes mapped to the Y-chromosome have been established as critical to normal testicular development and spermatogenesis, certain autosomal genes are now also recognized as important in these processes. Here we present clinical evidence to support the Luciani-Guo hypothesis (first advanced in 1984 and refined in 2002), which predicts severe spermatogenic impairment with aberrations involving chromosomes 9, 13, and/or 14, independent of Y-chromosome status. Additional study including fluorescent in situ hybridization and molecular analysis of specific chromosomal regions is needed to characterize more fully the contribution(s) of these autosomes to male testicular development and spermatogenesis.


Improved method for recovery of bacteriophage from large volumes of water using negatively charged microporous filters.
Current virus-recovery procedures using negatively charged microporous filters provide an inexpensive, reliable method for the recovery and detection of enteroviruses from water and wastewater; however, adjustment of the test samples to pH 3.5 to promote enterovirus adsorption results in significant inactivation of bacteriophage and an inability to simultaneously recover them from large volumes of water using this procedure. Procedures specifically designed for the detection of bacteriophage are currently in use but generally are only effective for small volumes of water. Positively charged filters can be used to recover both enteroviruses and bacteriophage from large volumes of water at neutral pH; however, the filters are expensive. The addition of manganese chloride to test solutions at pH 3.5 prior to filtration through negatively charged Filterite filters allowed for sampling of larger volumes of water by reducing the inactivation of bacteriophage and increasing the recovery of PRD1, MS2, and naturally isolated bacteriophage by a factor of four or five when compared with recoveries from solutions without MnCl2. This method provides an inexpensive, reliable alternative to large-volume bacteriophage recovery procedures that use positively charged filters at neutral pH.


Surface properties of the conidiospores of Phanerochaete chrysosporium and their relevance to pellet formation.
The conidiospores of the white rot basidiomycete Phanerochaete chrysosporium tend to aggregate during swelling and germination in agitated liquid medium; as time passes, the initial aggregates tend to associate together and to capture conidiospores that remain isolated. The surface chemical compositions of the conidiospores and of developed hyphae were analyzed by X-ray photoelectron spectroscopy. The data were interpreted by modelling the surface in terms of proteins, polysaccharides and hydrocarbonlike compounds. The surface molecular composition of the dormant conidiospores was estimated to be about 45% proteins, 20% carbohydrates, and 35% hydrocarbonlike compounds. There was an increase in the polysaccharide content during germination. Later, when the hyphae were developed, the polysaccharide content became still higher, and the protein content dropped. The initial step of aggregation is attributed to polysaccharide bridging; its occurrence cannot be explained by a change of the overall hydrophobicity or electrical properties of the conidiospores.


Pump-probe localization technique of varying solid contacts.
A baseline-free defect localization method in thin plates is proposed and tested. In this proof-of-concept work, a steel ball pressed against an aluminum plate is used to mimic a surface contact defect. The technique takes benefit of a repetitive nonlinear pump-probe interaction with a backpropagation imaging algorithm. High-frequency probe waves are periodically emitted by a piezoelectric patch transducer glued to the plate. Propagated flexural waves are recorded using a distributed array of transducers. At the same time, a continuous low-frequency pump vibration provided by a shaker fixed to the plate modulates the contact state. By combining multiple probe signals, the contact can be successfully localized. Contrast of the localization images is finally improved by a factor of 3 to 5 by implementing a modified version based on synchronous detection of the imaging algorithm.


[Successful epicardial ablation of a postinfarction ventricular tachycardia].
Endocardial radiofrequency catheter ablation was performed because of frequent, 150/min monomorphic ventricular tachycardia (VT). In February 2005 it was many times terminated only by ICD shock in a 55-year-old postinfarction patient who received an implantable cardioverter defibrillator (ICD) 5 years ago because of rapid, monomorphic VT. After being asymptomatic for two months, a slower, 120/min, however, incessant ventricular tachycardia was present which was untreatable by a repeated endocardial ablation. Combined antiarrhythmic treatment was not effective either. In June 2005, after another unsuccessful endocardial ablation, epicardial ablation was decided as an "ultimum refugium". After subxyphoidal percutaneous pericardial punction we positioned the ablation catheter in the pericardial space, and ablation at the earliest activation point terminated the permanently ongoing arrhythmia for one and a half month within 5 seconds. After another three ablations we were unable to induce ventricular arrhythmia even with programmed ventricular extrastimulation. During a three-year follow-up, ventricular tachycardia was noticed in only two cases, ICD terminated both arrhythmias with the first antitachycardia pacing. The patient is in NYHA stage II at present. According to our knowledge, our case is the first successful epicardial ablation of incessant ventricular tachycardia in a postinfarction patient in Hungary.


Intrinsic defect formation and the effect of transition metal doping on transport properties in a ductile thermoelectric material α-Ag2S: a first-principles study.
In this paper, the electronic structure and transport properties of a ductile thermoelectric material α-Ag2S are examined using first-principles calculations combined with the Boltzmann transport equation within a constant relaxation-time approximation. The use of the exchange-correlation functional SCAN + rVV10 successfully describes the geometric and electronic structure of α-Ag2S with a direct bandgap value of 0.99 eV, which is consistent with the previous experimental observations. Based on the calculations of the formation energy of typical intrinsic defects, it is found that intrinsic defect formation greatly affects the conductivity of the system where silver vacancy and interstitial silver act as p-type and n-type defects, respectively. Large Seebeck coefficients at room-temperature, of around -760 μV K-1 for n-type and 1400 μV K-1 for p-type, are realized. It is also suggested that the doping of fully filled d-block elements such as Cu and Au not only maintained the Seebeck coefficients at high values but also improved electrical conductivity by more than 1.4 times, leading to the improvement of the power factor by up to 40% compared to the non-doped sample at low carrier concentration.


Pterostilbene leads to DNMT3B-mediated DNA methylation and silencing of OCT1-targeted oncogenes in breast cancer cells.
Transcription factor (TF)-mediated regulation of genes is often disrupted during carcinogenesis. The DNA methylation state of TF-binding sites may dictate transcriptional activity of corresponding genes. Stilbenoid polyphenols, such as pterostilbene (PTS), have been shown to exert anticancer action by remodeling DNA methylation and gene expression. However, the mechanisms behind these effects still remain unclear. Here, the dynamics between oncogenic TF OCT1 binding and de novo DNA methyltransferase DNMT3B binding in PTS-treated MCF10CA1a invasive breast cancer cells has been explored. Using chromatin immunoprecipitation (ChIP) followed by next generation sequencing, we determined 47 gene regulatory regions with decreased OCT1 binding and enriched DNMT3B binding in response to PTS. Most of those genes were found to have oncogenic functions. We selected three candidates, PRKCA, TNNT2, and DANT2, for further mechanistic investigation taking into account PRKCA functional and regulatory connection with numerous cancer-driving processes and pathways, and some of the highest increase in DNMT3B occupancy within TNNT2 and DANT2 enhancers. PTS led to DNMT3B recruitment within PRKCA, TNNT2, and DANT2 at loci that also displayed reduced OCT1 binding. Substantial decrease in OCT1 with increased DNMT3B binding was accompanied by PRKCA promoter and TNNT2 and DANT2 enhancer hypermethylation, and gene silencing. Interestingly, DNA hypermethylation of the genes was not detected in response to PTS in DNMT3B-CRISPR knockout MCF10CA1a breast cancer cells. It indicates DNMT3B-dependent methylation of PRKCA, TNNT2, and DANT2 upon PTS. Our findings provide a better understanding of mechanistic players and their gene targets that possibly contribute to the anticancer action of stilbenoid polyphenols.


Influence of continuous mining arrangements on respirable dust exposures.
In underground continuous mining operations, ventilation, water sprays and machine-mounted flooded-bed scrubbers are the primary means of controlling respirable dust exposures at the working face. Changes in mining arrangements - such as face ventilation configuration, orientation of crosscuts mined in relation to the section ventilation and equipment operator positioning - can have impacts on the ability of dust controls to reduce occupational respirable dust exposures. This study reports and analyzes dust concentrations measured by the Pittsburgh Mining Research Division for remote-controlled continuous mining machine operators as well as haulage operators at 10 U.S. underground mines. The results of these respirable dust surveys show that continuous miner exposures varied little with depth of cut but are significantly higher with exhaust ventilation. Haulage operators experienced elevated concentrations with blowing face ventilation. Elevated dust concentrations were observed for both continuous miner operators and haulage operators when working in crosscuts driven into or counter to the section airflow. Individual cuts are highlighted to demonstrate instances of minimal and excessive dust exposures attributable to particular mining configurations. These findings form the basis for recommendations for lowering face worker respirable dust exposures.


Minimally invasive concomitant cardiac procedures and repair of pectus excavatum: case report.
A minimally invasive concomitant repair of an atrial-septal defect II with patent ductus arteriosus and pectus excavatum, using a substernal steel bar was successfully done in a 10-year-old girl. Postoperative outcomes and cosmetic appearance were excellent. Therefore, a simultaneous repair of pectus excavatum with cardiac lesions performed in a minimally invasive way is feasible and should be considered, particularly in female children.


Modified physiological and operative score for the enumeration of mortality and morbidity risk assessment model in general surgery.
To establish a scoring system for predicting the incidence of postoperative complications and mortality in general surgery based on the physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM), and to evaluate its efficacy. Eighty-four patients with postoperative complications or death and 172 patients without postoperative complications, who underwent surgery in our department during the previous 2 years, were retrospectively analyzed by logistic regression. Fifteen indexes were investigated including age, cardiovascular function, respiratory function, blood test results, endocrine function, central nervous system function, hepatic function, renal function, nutritional status, extent of operative trauma, and course of anesthesia. Modified POSSUM (M-POSSUM) was developed using significant risk factors with its efficacy evaluated. The significant risk factors were found to be age, cardiovascular function, respiratory function, hepatic function, renal function, blood test results, endocrine function, nutritional status, duration of operation, intraoperative blood loss, and course of anesthesia. These factors were all included in the scoring system. There were significant differences in the scores between the patients with and without postoperative complications, between the patients died and survived with complications, and between the patients died and survived without complications. The receiver operating characteristic curves showed that the M-POSSUM could accurately predict postoperative complications and mortality. M-POSSUM correlates well with postoperative complications and mortality, and is more accurate than POSSUM.


Airline networks and the international diffusion of severe acute respiratory syndrome (SARS).
In fewer than four months in 2003, severe acute respiratory syndrome (SARS) spread from China to 25 countries and Taiwan, becoming the first new, easily transmissible infectious disease of the twenty-first century. The role of air transport in the diffusion of the disease became obvious early in the crisis; to assess that role more carefully, this study relates the spatial-temporal pattern of the SARS outbreak to a measure of airline network accessibility. Specifically, the accessibility from those countries that were infected by SARS, beginning with China, to other countries was measured using airline schedules. The country-pair accessibility measure, along with other country-level factors relevant to the disease, were tested as determinants of the speed with which SARS arrived in infected countries as well as its failure to arrive in most countries. The analyses indicate that airline network accessibility was an especially influential variable but also that the importance of this variable diminished in the latter weeks of the outbreak. The latter finding is partly attributable to public health measures, particularly health screening in airports. The timing and geography of those measures are reviewed using data from media reports and interim World Health Organization (WHO) documents during the outbreak. The uneven effort to curtail the international diffusion of SARS suggests further planning is needed to develop a concerted response to contain future epidemics.


Two different clones of Candida pelliculosa bloodstream infection in a tertiary neonatal intensive care unit.
Fungemia in preterm infants results in high mortality and morbidity. The genotypes, drug susceptibilities of Candida pelliculosa strains, and clinical features of two outbreaks of neonatal candidemia caused by C. pelliculosa were analyzed, in order to provide evidence for the outbreaks and characteristics of C. pelliculosa neonatal candidemia. The strains were genotyped by pulsed-field gel electrophoresis to investigate their genetic relatedness. The broth microdilution method was used to determine in vitro susceptibility of the isolates to antifungal drugs. Clinical features of the infected patients were collected to analyze the risks for C. pelliculosa infection. Fourteen neonates, hospitalized in the neonatal intensive care unit from November 2012 to October 2013, were infected by C. pelliculosa. All 14 patients were cured after treatment with fluconazole and discharged without any complications. The C. pelliculosa isolates from the 14 patients were clustered into two groups, indicating that the outbreaks were caused by two types of strains. Eight of nine strains isolated from the 2013 outbreak were clustered into the same group, while one isolate was grouped together with five isolates from the 2012 outbreak. In vitro experiments demonstrated high antifungal activity of fluconazole, voriconazole, amphotericin B, and 5-fluorocytosine to C. pelliculosa. The common symptoms of C. pelliculosa candidaemia were fever, cyanosis, polypnea, hypoactivity, and apnea. The current study revealed high in vitro susceptibility of C. pelliculosa to antifungals. As C. pelliculosa candidaemia cannot be characterized by clinical symptoms and routine blood testing alone, monitoring unusual strains isolated from immunodeficient hosts is very important to prevent possible outbreaks.


Contemporary Review of Grafting Techniques for the Surgical Treatment of Peyronie's Disease.
Peyronie's disease (PD) is a benign fibrotic disorder of the tunica albuginea of the penis, which can cause penile pain, curvature, shortening, erectile dysfunction, and psychological distress. Surgery is indicated when penile curvature prevents satisfactory sexual intercourse. Plaque incision or excision with grafting has been suggested as an option in patients with a penile curvature greater than 60°, a shortened penis, and/or an hourglass or complex deformity. To provide an overview of recent studies reporting outcomes of grafting techniques and to report advances in the development of new grafting materials for PD surgery. A literature review was performed through PubMed from 2011 through 2016 regarding grafting techniques for PD. Key words used for the search were grafting techniques, grafts, graft materials, Peyronie's disease, surgical outcomes, and surgical therapy. To report on novel and promising graft materials for PD and to discuss surgical techniques, outcomes, and limitations. Discussed outcomes include postoperative penile straightening, shortening, erectile function, glans sensation, and patient satisfaction. Various surgical techniques and grafting materials can be used for the coverage of the tunica albuginea defect after partial plaque excision or incision. Autologous and non-autologous grafts have been used in this setting. A major advantage of the available "off-the-shelf" grafts is that they do not require donor site harvesting, thus decreasing morbidity and operative time. Tissue-engineered grafts represent the future, but more research is needed to further improve surgical handling and postoperative outcomes. Patients opting for grafting techniques should have sufficient erectile rigidity preoperatively. Surgeon experience, careful patient selection, patient preference, and type of penile deformity affect the choice of graft and surgical approach used. Hatzichristodoulou G, Osmonov D, Kübler H, et al. Contemporary Review of Grafting Techniques for the Surgical Treatment of Peyronie's Disease. Sex Med Rev 2017;5:544-552.


The application of HSP70 as a target for gene therapy.
The 70-kDa heat shock proteins (HSP70s) are well-studied and characterized heat shock proteins (HSPs). They constitute essential components of a quality control system of protein synthesis, and function as molecular chaperones to prevent proteins from misfolding and aggregating during both de novo synthesis and under conditions of stress. Moreover, it is now well established that HSP70s play important cytoprotective roles in various pathological settings. Recognition of molecular chaperone and cytoprotective functions of HSP70s is fostering active investigations into the potential of HSP70s as therapeutic targets at the laboratory level. Gaining insight into these recent advances may have profound implications in the development of HSP70-based clinical studies.


Circular RNAs in digestive system cancer: potential biomarkers and therapeutic targets.
Circular RNAs (circRNAs) are a series of special closed circular RNA molecules with stability and conservatism. In recent years, advances in high-throughput RNA sequencing technology have led to explosive discovery of circRNAs in different types of species and cells. Moreover, circRNAs can accomplish a remarkable multitude of biological functions, such as regulating transcription or splicing, serving as miRNA sponges, interacting with RNA-binding proteins, and translating proteins. Meanwhile, circRNAs involve in the biogenesis and development of many diseases, including cardiovascular disorders, nervous system disorders, cancers, etc. Herein, we discuss the latest research progress of circRNA, as well as their diagnostic and prognostic significance in digestive system cancers. In addition, this paper highlights that circRNAs might serve as potential therapeutic targets for novel drugs by taking digestive system cancer as an illustrative example.


Quality of life of children with benign rolandic epilepsy.
The first objective of this study was to determine the quality of life of children with benign rolandic epilepsy. Secondly, this investigation aimed to predict the influence of cognition on quality of life, controlling for the emotional impact of the epilepsy on the parent. Initial recruitment was through the major electroencephalography laboratories of metropolitan Sydney. The syndrome was defined using the International League Against Epilepsy classification. Patients underwent a comprehensive cognitive assessment, and parents completed the Child Health Questionnaire, Child Behavior Checklist, and Quality of Life in Childhood Epilepsy Questionnaire. Parental emotional impact was assessed using a subscale from the Child Health Questionnaire. The cohort included 30 patients (22 males, 8 females), mean age 9.67 years. There was a higher incidence of competence problems compared with normative data. The average psychosocial score was significantly lower than normative data. Controlling for parental emotional impact, general intellectual ability predicted quality of life in the areas of self-esteem and language. Clinical variables had minimal impact and were not included in the regression models. Parental emotional impact, however, was a major independent predictor of quality of life. Quality of life may be compromised in children with benign rolandic epilepsy and is related to cognitive variables and emotional impact of the epilepsy on the parent.


Improving self-awareness of prospective memory function after TBI using experiential feedback on a board game activity: An observational study.
This study investigated whether experiential and video feedback on performance of prospective memory (PM) tasks embedded within a board game activity improved self-awareness of PM function in adults with moderate-severe traumatic brain injury. An observational pre-post study design with 26 participants from a larger trial of a 6-session PM rehabilitation programme. Sessions 3 and 4 included a board game activity with embedded time-, event-, and activity-based PM tasks. Verbal feedback was provided by therapists during the game and video feedback afterwards. Self-ratings of performance were used to divide the sample into under-estimators (n = 7), accurate estimators (n = 9) and over-estimators (n = 10) of actual PM performance. The discrepancy between self- and therapist ratings of PM performance was measured before and after the game, and following video feedback, and compared between timepoints using non-parametric statistics. Post-task self-evaluations were more accurate than pre-task self-evaluations for the under- and over-estimator groups. Under-estimators showed significant improvement in accuracy of ratings for activity-based PM. Over-estimators showed improvement for event-based PM. Further improvements after video feedback were not significant. The board game activity provided a vehicle for experiential feedback and a means of engaging both those with impaired self-awareness and heightened self-awareness of PM in cognitive rehabilitation.


Involvement of ILC1-like innate lymphocytes in human autoimmunity, lessons from alopecia areata.
Here, we have explored the involvement of innate lymphoid cells-type 1 (ILC1) in the pathogenesis of alopecia areata (AA), because we found them to be significantly increased around lesional and non-lesional HFs of AA patients. To further explore these unexpected findings, we first co-cultured autologous circulating ILC1-like cells (ILC1lc) with healthy, but stressed, organ-cultured human scalp hair follicles (HFs). ILClc induced all hallmarks of AA ex vivo: they significantly promoted premature, apoptosis-driven HF regression (catagen), HF cytotoxicity/dystrophy, and most important for AA pathogenesis, the collapse of the HFs physiological immune privilege. NKG2D-blocking or IFNγ-neutralizing antibodies antagonized this. In vivo, intradermal injection of autologous activated, NKG2D+/IFNγ-secreting ILC1lc into healthy human scalp skin xenotransplanted onto SCID/beige mice sufficed to rapidly induce characteristic AA lesions. This provides the first evidence that ILC1lc, which are positive for the ILC1 phenotype and negative for the classical NK markers, suffice to induce AA in previously healthy human HFs ex vivo and in vivo, and further questions the conventional wisdom that AA is always an autoantigen-dependent, CD8 +T cell-driven autoimmune disease.


Predicting contrast-induced nephropathy after CT pulmonary angiography in the critically ill: a retrospective cohort study.
It is uncertain whether we can predict contrast-induced nephropathy (CIN) after CT pulmonary angiography (CTPA). This study compared the ability of a validated CIN prediction score with the Pulmonary Embolism Severity Index (PESI) in predicting CIN after CTPA. This cohort study involved critically ill adult patients who required a CTPA to exclude acute pulmonary embolism (PE). Patients with end-stage renal failure requiring dialysis were excluded. CIN was defined as an elevation in plasma creatinine concentrations > 44.2μmol/l (or 0.5 mg/dl) within 48 h after CTPA. Of the 137 patients included, 77 (51%) were hypotensive, 54 (39%) required inotropic support, and 68 (50%) were mechanically ventilated prior to the CTPA. Acute PE was confirmed in 21 patients (15%) with 14 (10%) being bilateral. CIN occurred in 56 patients (41%) with 35 (26%) required dialysis subsequent to CTPA. The CIN prediction score had a good ability to discriminate between patients with and without developing CIN (Area under the receiver-operating-characteristic (AUROC) curve 0.864, 95% confidence interval [CI] 0.795-0.916) and requiring subsequent dialysis (AUROC 0.897, 95% CI 0.833-0.942) and was better than the PESI in predicting both outcomes (AUROC 0.731, 95% CI 0.649-0.804 and 0.775, 95% CI 0.696-0.842, respectively). A CIN risk score > 10 and 12 had an 82.1 and 85.7% sensitivity and 81.5 and 78.4% specificity to predict subsequent CIN and dialysis, respectively. The CIN prediction model tended to underestimate the observed risks of dialysis, but this was improved after recalibrating the slope and intercept of the original prediction equation. The CIN prediction score had a good ability to discriminate between critically ill patients with and without developing CIN after CTPA. Used together for critically ill patients with suspected acute PE, the CIN prediction score and PESI may be useful to inform clinicians when the benefits of a CTPA scan will outweigh its potential harms.


Ultrafiltration to remove endotoxins and other cytokine-inducing materials from tissue culture media and parenteral fluids.
The presence of small amounts of endotoxins are often undesirable when investigating cytokines such as interleukin-1 and tumor necrosis factor alpha. Polymyxin B, widely used to block endotoxins, does not block several forms of endotoxins, and at high concentrations, polymyxin B itself stimulates interleukin-1 production. Human peripheral blood mononuclear cells are highly sensitive to endotoxins; they respond with cytokine production to endotoxins at concentrations of 10-50 pg/ml and detect pyrogenic materials nonreactive in the Limulus test. In the present study, ultrafiltration using polysulfone filters was found to remove all interleukin-1- and tumor necrosis factor alpha-inducing substances produced in E. coli cultures. Interleukin-1- and tumor necrosis factor alpha-inducing substances derived from Pseudomonas aeruginosa cultures were also rejected by the filters. Ultrafiltration is therefore a convenient and effective procedure to remove interleukin-1 and tumor necrosis factor alpha-inducing substances from parenteral fluids and solutions that come in contact with blood such as fluids used in hemodialysis. This technique is also applicable for the large-scale production of culture media for mammalian cell expression of recombinant, pyrogen-free proteins intended for use in humans.


[Insulinoma. Clinical and surgical considerations concerning a case].
Insulinoma is the most common endocrine tumor of the pancreas. It arises from the beta-islet cells of Langerhans. Insulinomas synthesize and secrete insulin autonomously in the presence of low blood glucose levels, causing spontaneous hypoglycemia and characteristic clinical symptoms. The authors examined data the from the most important international research projects on this topic during the past 20 years. Insulinomas are rare, with an annual incidence of 0.5 per million population. Up to 90% patients have benign solitary pancreatic insulinomas. People of all ages can be affected with this neoplasm. The authors reported a case of a large insulinoma of the body and tail of the pancreas, with atypical psychic symptoms. A distal pancreatectomy with splenectomy was performed. No surgical complications occurred in the postoperative course. The psychic symptoms were emphasized with refusal of food. The patient underwent Parenteral Nutrition and was discharged 24 days after the operation. The surgical removal of the tumor permitted the patient to recover completely, with glucose and insulin blood levels in normal range.


Mathematical modeling of Dengue virus serotypes propagation in Mexico.
The Dengue virus (DENV) constitutes a major vector borne virus disease worldwide. Prediction of the DENV spread dynamics, prevalence and infection rates are crucial elements to guide the public health services effort towards meaningful actions. The existence of four DENV serotypes further complicates the virus proliferation forecast. The different serotypes have varying clinical impacts, and the symptomatology of the infection is dependent on the infection history of the patient. Therefore, changes in the prevalent DENV serotype found in one location have a profound impact on the regional public health. The prediction of the spread and intensity of infection of the individual DENV serotypes in specific locations would allow the authorities to plan local pesticide spray to control the vector as well as the purchase of specific antibody therapy. Here we used a mathematical model to predict serotype-specific DENV prevalence and overall case burden in Mexico.


Electroacupuncture Treatment Suppresses Transcription Factor IRF8 in Spinal Cord of Rats with Spared Nerve Injury.
Neuropathic pain with complex mechanisms has become a major public health problem that greatly impacts patients' quality of life. Therefore, novel and more effective strategies against neuropathic pain need further investigation. Electroacupuncture (EA) has an ameliorating effect on neuropathic pain following spared nerve injury (SNI), but the underlying mechanism remains to be fully clarified. Interferon regulatory factor 8 (IRF8), a critical transcription factor, was reported to be involved in the modulation of neuropathic pain. Here, we focused on exploring whether 2 Hz EA stimulation exerts an inhibitory action on spinal IRF8 in SNI rats. In this study, SNI rats were treated with 2 Hz EA once every other day for 21 days. Paw withdrawal threshold (PWT) was applied to determine the analgesic effect of 2 Hz EA on SNI rats. The spinal IRF8 and CX3CRl expressions were detected with qRT-PCR and western blot, and immunofluorescence staining was used to evaluate colocation of IRF8 or CX3CRl with microglial activation marker CD11b in the spinal cord. It was found that SNI induced significant elevation of spinal IRF8 and CX3CRl mRNA and protein expression. Additionally, immunofluorescence results showed that SNI elicited the coexpression of IRF8 with CD11b, as well as CX3CRl with CD11b in the spinal cord. Meanwhile, 2 Hz EA treatment of SNI rats not only reduced IRF8 and CX3CRl mRNA and protein expression, but also reversed the coexpression of IRF8 or CX3CRl with CD11b in the spinal cord, along with an attenuation of SNI-evoked mechanical hypersensitivity. This experiment highlighted that 2 Hz EA can inhibit IRF8 expression and microglial activation in the spinal cord of SNI rats. Hence, targeting IRF8 may be a promising therapeutic strategy for 2 Hz EA treatment of neuropathic pain.


[Investigation of O25b-ST131 Clone Frequency and Presence of Carbapenem and Fosfomycin Resistance Genes in Escherichia coli Isolates: First Detection of fosA3 from Escherichia coli O25bSTf131 Clone from Türkiye].
Escherichia coli ST131 clone was first reported in 2008 and defined as a 'high-risk pandemic clone'. This clone plays a critical role in the spread of antimicrobial resistance worldwide. It was reported in many studies that the E.coli ST131 clone is widespread worldwide and can carry virulence and antibiotic resistance genes. E.coli ST131 clone is associated with a fluoroquinolone and broad-spectrum cephalosporin resistance. The agents used in the treatment of infections caused by the E.coli ST131 clone are limited. For this reason, monitoring the resistance status of these limited agents is crucial. In this study, we aimed to investigate the prevalence of the O25b-ST131 clone, and the presence of carbapenem and fosfomycin resistance genes in fluoroquinolone-resistant E.coli isolates isolated from mid-stream urine samples. For the detection of the O25b-ST131 clone in fluoroquinolone-resistant E.coli isolates, amplification was performed with primers O25pabBspe-F and O25pabBspe-R. For the determination of resistance genes, carbapenem resistance genes blaNDM, blaVIM, blaKPC, blaIMP, and blaOXA-48 in carbapenem resistant isolates and plasmid-mediated fosfomycin resistance genes fosA3 and fosC2 in fosfomycin resistant isolates were investigated by multiplex PCR method. According to PCR results, the prevalence of E.coli O25b-ST131 isolates was 51.2%. Carbapenem resistance rate was 3.41%, and fosfomycin resistance rate was 3.41% in fluoroquinolone-resistant E.coli isolates. Carbapenem and fosfomycin resistance rates in E.coli O25bST131 isolates were determined as 0.83% and 2.5%, respectively. At least one of the carbapenem-resistance genes (blaNDM and/or blaOXA-48) was detected in six of the eight carbapenem-resistant isolates. Fosfomycin resistance gene fosA3 was seen in four of eight fosfomycin-resistant isolates. fosC2 gene was not detected in any of the isolates. In addition, the plasmid-mediated fosfomycin resistance gene fosA3 was detected in an E.coli O25b-ST131 isolate, and this result was confirmed by sequence analysis. To the best of our knowledge, this is the second report about fosA3 positivity in E.coli ST131 isolates from the world and the first reported from Europe and Türkiye. As a result, approximately half of the fluoroquinolone-resistant E.coli isolates were identified as E.coli ST131 clones. Despite the high rate of this clone, the carbapenem and fosfomycin resistance rates are still relatively low, which is pleasing for the future of treatment. However, it should not be forgotten that resistance rates and the prevalence of resistance genes should be constantly monitored.


Economic injury level for second-generation cottonwood leaf beetle (Coleoptera: Chrysomelidae) in two-year-old Populus.
The cottonwood leaf beetle, Chrysomela scripta F., is a major defoliating pest of Populus in North America. As the use of Populus in short-rotation woody crop plantations continues to increase, there are increasing economic and environmental needs to develop rational pest management programs to reduce the impact of this insect. Our objective was to determine the economic injury levels for the second generation of the cottonwood leaf beetle during plantation establishment. Integrating the cost of the management, market value, insect injury, and host response to the injury, the economic injury levels for second generation cottonwood leaf beetle on 2-yr-old Populus were determined to be from 0.2 to 0.9 egg masses per actively growing terminal.


Prevalence of transfusion-transmitted virus infection in patients on maintenance hemodialysis from New Delhi, India.
Transfusion-transmitted virus (TTV) has been reported from a number of hemodialysis (HD) units from various countries throughout the world. TTV has been associated with liver diseases, viral hepatitis B, and C. Clinical details and information regarding TTV prevalence from India are insufficient. The prevalence and clinical significance of TTV infection were studied in New Delhi, India in HD patients. Serum samples were derived from 75 patients on maintenance HD, and 75 age- and sex-matched voluntary blood donors were examined for TTV viremia by nested polymerase chain reaction (PCR) using primers derived from UTR (A) region of the TTV genome. The prevalence of TTV DNA in patients on HD (83%) was significantly (p<0.05) higher than in blood donors (43%). Clinical background including the mean age, sex, mean duration of HD, and mean alanine aminotransferase (ALT) levels did not differ significantly between TTV DNA-positive and -negative HD patients. Fifty-four (72%) TTV-positive HD patients and 7 (56%) TTV-negative HD patients had blood transfusion histories (p>0.05). Among TTV-positive patients, Hepatitis B virus (HBV) co-infection was present in 14.2% cases while hepatitis C virus (HCV) co-infection was absent. Persistent elevation of ALT levels was observed in 7(9.3%) HD patients; 3 (43%) of them were TTV positive and 4 (57%) were TTV negative (p>0.05). All 3 TTV-positive patients with elevated ALT levels were co-infected with HBV. Patients with TTV infection alone showed normal ALT levels. Prevalence of TTV infection is high in North Indian patients on maintenance HD. Also, none of the exclusively TTV DNA-positive patients had clinical or biochemical signs of liver disease. TTV seems to spread through parenteral routes. More often, TTV seems to be associated with parenterally transmitted virus HBV, indicating a parenteral mode of TTV transmission. The pathogenicity of TTV remains unclear from the present study.


The Impact of Tic Severity, Comorbidity and Peer Attachment on Quality of Life Outcomes and Functioning in Tourette's Syndrome: Parental Perspectives.
The aim of this controlled, community-based study based on data from parents of youth (aged 7-16 years) with Tourette's syndrome (TS; n = 86) and parents of age and gender matched peers (n = 108) was to test several hypotheses involving a range of variables salient to the TS population, including peer attachment, quality of life, severity of tics, comorbidity, and psychological, behavioural and social dysfunction. Multivariate between-group analyses confirmed that TS group youth experienced lower quality of life, increased emotional, behavioural and social difficulties, and elevated rates of insecure peer attachment relative to controls, as reported by their primary caregiver. Results also confirmed the main hypothesis that security of peer attachment would be associated with individual variability in outcomes for youth with TS. As predicted, multivariate within-TS group analyses determined strong relationships among adverse quality of life outcomes and insecure attachment to peers, increased tic severity, and the presence of comorbid disorder. Findings suggest that youth with TS are at increased risk for insecure peer attachment and that this might be an important variable impacting the quality of life outcomes for those diagnosed.


Content, participants and outcomes of three diabetes care programmes in three low and middle income countries.
To improve access and quality of diabetes care for people in low-income countries, it is important to understand which elements of diabetes care are effective. This paper analyses three diabetes care programmes in the DR Congo, Cambodia and the Philippines. Three programmes offering diabetes care and self-management were selected. Programme information was collected through document review and interviews. Data about participants' characteristics, health outcomes, care utilisation, expenditures, care perception and self-management were extracted from a study database. Comparative univariate analyses were performed. Kin-réseau (DR Congo) is an urban primary care network with 8000 patients. MoPoTsyo (Cambodia) is a community-based peer educator network, covering 7000 patients. FiLDCare (Philippines) is a programme in which 1000 patients receive care in a health facility and self-management support from a community health worker. Content of care of the programmes is comparable, the focus on self-management largest in MoPoTsyo. On average, Kin-réseau patients have a higher age, longer diabetes history and more overweight. MoPoTsyo includes most female, most illiterate and most lean patients. Health outcomes (HbA1C level, systolic blood pressure, diabetes foot lesions) were most favourable for MoPoTsyo patients. Diabetes-related health care expenditure was highest for FiLDCare patients. This study shows it possible to maintain a diabetes programme with minimal external resources, offering care and self-management support. It also illustrates that health outcomes of persons with diabetes are determined by their bio-psycho-social characteristics and behaviour, which are each subject to the content of care and the approach to chronic illness and self-management of the programme, in turn influenced by the larger context.


A pilot randomized controlled trial of an oral care intervention to reduce mucositis severity in stem cell transplant patients.
Oral mucositis remains a significant problem in autologous stem cell transplantation (ASCT). This pilot trial assessed the effectiveness of oral cryotherapy plus an oral care protocol in reducing oral mucositis severity in ASCT patients. Patients admitted for ASCT were randomly allocated to either the experimental arm (n=23) or usual care (n=23). All participants received information on principles of good oral hygiene and skills training in oral self-care. Patients in the experimental arm had a 60-minute regimen of oral cryotherapy. The primary outcome of oral mucositis severity and secondary outcomes of mucositis-related pain and functional intake of food and fluids were measured at Days -1, 3, 6, 9, and 12. Length of hospital stay was determined by counting backward from discharge day to admission. Perception of tolerability and acceptability of the 60-minute cryotherapy and frequency of the oral care regimen also were assessed. Forty-eight patients were recruited at the study site in six months. The overall mean (SE) of oral mucositis severity for the experimental arm was significantly lower than that for the control group: 0.43 (0.12) vs. 1.14 (0.12); P<0.001, on a 0-4 scale. The overall mean (SE) mucositis-related pain score for the experimental arm also was significantly lower than that for the control group: 0.30 (0.23) vs. 1.64 (0.24); P<0.001, on a 0-10 scale. Oral cryotherapy plus an oral care protocol appears to be beneficial in reducing severity of mucositis compared with an oral care protocol alone.


De Novo Transcriptome Assembly, Gene Annotations, and Characterization of Functional Profiling Reveal Key Genes for Lead Alleviation in the Pb Hyperaccumulator Greek Mustard (Hirschfeldia incana L.).
Lead (Pb) contamination is a widespread environmental problem due to its toxicity to living organisms. Hirschfeldia incana L., a member of the Brassicaceae family, commonly found in the Mediterranean regions, is characterized by its ability to tolerate and accumulate Pb in soils and hydroponic cultures. This plant has been reported as an excellent model to assess the response of plants to Pb. However, the lack of genomic data for H. incana hinders research at the molecular level. In the present study, we carried out RNA deep transcriptome sequencing (RNA-seq) of H. incana under two conditions, control without Pb(NO3)2 and treatment with 100 µM of Pb(NO3)2 for 15 days. A total of 797.83 million reads were generated using Illumina sequencing technology. We assembled 77,491 transcript sequences with an average length of 959 bp and N50 of 1330 bp. Sequence similarity analyses and annotation of these transcripts were performed against the Arabidopsis thaliana nr protein database, Gene Ontology (GO), and KEGG databases. As a result, 13,046 GO terms and 138 KEGG maps were created. Under Pb stress, 577 and 270 genes were differentially expressed in roots and aboveground parts, respectively. Detailed elucidation of regulation of metal transporters, transcription factors (TFs), and plant hormone genes described the role of actors that allow the plant to fine-tune Pb stress responses. Our study revealed that several genes related to jasmonic acid biosynthesis and alpha-linoleic acid were upregulated, suggesting these components' implication in Hirschfeldia incana L responses to Pb stress. This study provides data for further genomic analyses of the biological and molecular mechanisms leading to Pb tolerance and accumulation in Hirschfeldia incana L.


Regulation of interleukin-12 by complement receptor 3 signaling.
Complement receptor type 3 (CR3, CD11b/CD18) serves as a receptor for a number of endogenous ligands and infectious organisms, and is involved in adhesion and host defense functions. Here, we report that signaling via CR3 plays an important role in regulating production of interleukin-12 (IL-12), a key mediator of cell-mediated immunity (CMI). We demonstrate with a variety of stimuli a dose-dependent, specific downregulation of IL-12 secretion by human monocytes in vitro after exposure to antibodies to CR3 (anti-CD11b and anti-CD18), as well as to the natural CR3 ligands, iC3b, and Histoplasma capsulatum. CR3 antibodies also suppressed interferon-gamma (IFN-gamma) production in cultures of human peripheral blood mononuclear cells (PBMC). We determined that one mechanism by which CR3 antibodies may suppress IL-12 production is by the inhibition of IFN-gamma-induced tyrosine phosphorylation. Finally, in a murine model of IL-12-dependent septic shock, we provide evidence that administration of CR3 antibodies leads to suppression of IL-12 and IFN-gamma in vivo. Our studies thus define a novel role for CR3 in regulating CMI functions via IL-12.


Luminally Acting Agents for Constipation Treatment: A Review Based on Literatures and Patents.
Constipation is one of the most frequently reported gastrointestinal (GI) disorders that negatively impacts quality of life and is associated with a significant economic burden to the patients and society. Traditional treatments including lifestyle modification and laxatives are often ineffective in the more severe forms of constipation and over the long term. New medications targeting at intestinal chloride channels and colonic serotonin receptors have been demonstrated effective in recent years. Emerging agents focusing on improving intestinal secretion and/or colonic motility have been shown effective in animal models and even in clinical trials. Recognization of the role of cystic fibrosis transmembrane regulator (CFTR) and calcium-activated chloride channels (CaCCs) in intestine fluid secretion and motility modulation makes CFTR and CaCCs promising molecule targets for anti-constipation therapy. Although there are multiple choices for constipation treatment, there is still a recognized need for new medications in anti-constipation therapy. The present review covers the discovery of luminally acting agents for constipation treatment described in both patents (2011-present) and scientific literatures.


Increase in proteins involved in mitochondrial fission, mitophagy, proteolysis and antioxidant response in type I endometrial cancer as an adaptive response to respiratory complex I deficiency.
Pathogenic mtDNA mutations associated with alterations of respiratory complex I, mitochondrial proliferation (oncocytic-like phenotype) and increase in antioxidant response were previously reported in type I endometrial carcinoma (EC). To evaluate whether in the presence of pathogenic mtDNA mutations other mitochondrial adaptive processes are triggered by cancer cells, the expression level of proteins involved in mitochondrial dynamics, mitophagy, proteolysis and apoptosis were evaluated in type I ECs harboring pathogenic mtDNA mutations and complex I deficiency. An increase in the fission protein Drp1, in the mitophagy protein BNIP3, in the mitochondrial protease CLPP, in the antioxidant and anti-apoptotic protein ALR and in Bcl-2 as well as a decrease in the fusion protein Mfn2 were found in cancer compared to matched non malignant tissue. Moreover, the level of these proteins was measured in type I EC, in hyperplastic (the premalignant form) and in non malignant tissues to verify whether the altered expression of these proteins is a common feature of endometrial cancer and of hyperplastic tissue. This analysis confirmed in type I EC samples, but not in hyperplasia, an alteration of the expression level of these proteins. These results suggest that in this cancer mitochondrial fission, antioxidant and anti-apoptotic response may be activated, as well as the discharge of damaged mitochondrial proteins as adaptation processes to mitochondrial dysfunction.


Safety and efficacy of metallic stent for unresectable distal malignant biliary obstruction in elderly patients.
To study the safety of insertion of metallic stents in elderly patients with unresectable distal malignant biliary obstruction. Of 272 patients with unresectable distal malignant biliary obstruction, 184 patients under the age of 80 were classified into Group A, and 88 subjects aged 80 years or more were classified into Group B. The safety of metallic stent insertion, metal stent patency period, and the obstruction rate were examined in each group. In Group B, patients had a significantly worse performance status, high blood pressure, heart disease, cerebrovascular disease, and dementia; besides the rate of patients orally administered antiplatelet drugs or anticoagulants tended to be higher (P < 0.05). Metallic stents were successfully inserted in all patients. The median patency period was 265.000 ± 26.779 (1-965) d; 252.000 ± 35.998 (1-618) d in Group A and 269.000 ± 47.885 (1-965) d in Group B, with no significant difference between the two groups. Metallic stent obstruction occurred in 82 of the 272 (30.15%) patients; in 53/184 (28.80%) patients in Group A and in 29/88 (32.95%) of those in Group B, showing no significant difference between the two groups. Procedural accidents due to metal stent insertion occurred in 24/272 (8.8%) patients; in 17/184 (9.2%) of patients in Group A and in 7/88 (8.0%) of those in Group B, with no significant difference between the two groups, either. These results suggested that metallic stents can be safely inserted to treat unresectable distal malignant biliary obstruction even in elderly patients aged 80 years or more.


[Report on the capsule-dosage and mixing system. 4. Correctness and precision in the dosage of multi-component materials; pre-dosage in daily practice as a preliminary solution to the capsule-dosage and mixing system].
The significance of the factors "accuracy" and "precision" in the preparation of multicomponent materials is outlined with special regard to problems related to dosage. The present technological development permits to shift the responsibility for accuracy and precision to the manufacturers of dental materials. In view of the applicability of the capsule dosing and mixing system, the author presents an intermediate solution (based on the experimental verification of various dosing methods) that permits to benefit from the main advantages of the capsule system in everyday practice prior to the establishment of centralized dosing facilities.


Perception through visuomotor anticipation in a mobile robot.
Several scientists suggested that certain perceptual qualities are based on sensorimotor anticipation: for example, the softness of a sponge is perceived by anticipating the sensations resulting from a grasping movement. For the perception of spatial arrangements, this article demonstrates that this concept can be realized in a mobile robot. The robot first learned to predict how its visual input changes under movement commands. With this ability, two perceptual tasks could be solved: judging the distance to an obstacle in front by 'mentally' simulating a movement toward the obstacle, and recognizing a dead end by simulating either an obstacle-avoidance algorithm or a recursive search for an exit. A simulated movement contained a series of prediction steps. In each step, a multilayer perceptron anticipated the next image, which, however, became increasingly noisy. To denoise an image, it was split into patches, and each patch was projected onto a manifold obtained by modelling the density of the distribution of training patches with a mixture of Gaussian functions.


Polyclonal gammopathy with beta-globulin-gamma-globulin bridging. Two unusual cases.
Polyclonal gammopathy with beta-globulin-gamma-globulin (beta-gamma) bridging has been classically, though not exclusively, described with cirrhosis. We studied two unusual cases that exhibited polyclonal gammopathy with beta-gamma bridging. In the first case, the coexistence of Kaposi's sarcoma appeared with angioimmunoblastic lymphadenopathy. In the second, liver disease developed as a complication of alpha 1-antitrypsin deficiency and retroperitoneal malignant fibrous histiocytoma involving the porta hepatis.


Thermal behavior of a 13-molecule hydrogen cluster under pressure.
The thermal behavior of a 13-molecule hydrogen cluster is studied as a function of pressure and temperature using a combination of trajectory and density functional theory simulations. The analysis is performed in terms of characteristic descriptors such as caloric curve, root-mean-square bond length fluctuation, pair correlation function, velocity autocorrelation function, volume thermal expansion, and diffusion coefficients. The discussion addresses on the peculiarities of the transition from the ordered-to-disordered state as exhibited by the cluster under different pressures and temperatures.


Autologous tissue patch rich in stem cells created in the subcutaneous tissue.
To investigate whether we could create natural autologous tissue patches in the subcutaneous space for organ repair. We implanted the following three types of inert foreign bodies in the subcutaneous tissue of rats to produce autologous tissue patches of different geometries: (1) a large-sized polyvinyl tube (L = 25 mm, internal diameter = 7 mm) sealed at both ends by heat application for obtaining a large flat piece of tissue patch for organ repair; (2) a fine polyvinyl tubing (L = 25 mm, internal diameter = 3 mm) for creating cylindrically shaped grafts for vascular or nerve repair; and (3) a slurry of polydextran particle gel for inducing a bladder-like tissue. Implantation of inert materials was carried out by making a small incision on one or either side of the thoracic-lumbar region of rats. Subcutaneous pockets were created by blunt dissection around the incision into which the inert bodies were inserted (1 or 2 per rat). The incisions were closed with silk sutures, and the animals were allowed to recover. In case of the polydextran gel slurry 5 mL of the slurry was injected in the subcutaneous space using an 18 gauge needle. After implanting the foreign bodies a newly regenerated encapsulating tissue developed around the foreign bodies. The tissues were harvested after 4-42 d of implantation and studied by gross examination, histology, and histochemistry for organization, vascularity, and presence of mesenchymal stem cells (MSCs) (CD271+CD34+ cells). Implanting a large cylindrically shaped polyvinyl tube resulted in a large flat sheet of tissue that could be tailored to a specific size and shape for use as a tissue patch for repairing large organs. Implanting a smaller sized polyvinyl tube yielded a cylindrical tissue that could be useful for repairing nerves and blood vessels. This type of patch could be obtained in different lengths by varying the length of the implanted tube. Implanting a suspension of inert polydextran suspension gave rise to a bladder-like tissue that could be potentially used for repairing heart valves. Histologically, the three different types of tissue patches generated were organized similarly, consisting of three layers, increasing in thickness until day 14. The inner layer in contact with the inert material was avascular; a middle layer that was highly vascular and filled with matrix, and an outer layer consisting of loose connective tissue. MSCs identified as CD271+CD34+ cells were present in the medial layer and around major blood vessels at day 4 but absent at later time points. The early-harvested tissues, endowed with MSCs, could be used for tissue repair, while the later-harvested tissues, being less vascular but thicker and tougher, could be used as filler tissue for cosmetic purposes. An autologous, vascularized tissue patch of desired shape and size can be created in the subcutaneous space by implanting different types of inert bodies.


Deficient response inhibition as a cognitive endophenotype of ADHD.
To investigate whether a deficient response inhibition is a cognitive endophenotype of attention-deficit/hyperactivity disorder (ADHD). The authors hypothesized that nonaffected siblings of ADHD probands would have a response inhibition between that of ADHD probands and normal controls, although they resembled the controls at a behavioral level. Participants were 25 ADHD probands with a family history of ADHD, their nonaffected siblings (n = 25), and 48 normal controls matched for age and IQ. All participants were between 6 and 17 years of age. The nonaffected siblings were compared with their ADHD siblings and with controls on measures reflecting different types of response inhibition. The nonaffected siblings had results similar to those of the ADHD probands, who differed from the controls on all inhibition measures (p <.05). Siblings of ADHD probands, while not behaviorally expressing the disorder, have ADHD-associated deficits in response inhibition. This suggests that subtyping based on measures of response inhibition can help identify genetic susceptibility to ADHD. Children with a genetic vulnerability to ADHD may have hidden cognitive deficits in the absence of manifest behavioral symptoms. Therefore, they should be monitored to detect possible learning problems.


Clarifying Microbial Nitrous Oxide Reduction under Aerobic Conditions: Tolerant, Intolerant, and Sensitive.
One of the major challenges for the bioremediation application of microbial nitrous oxide (N2O) reduction is its oxygen sensitivity. While a few strains were reported capable of reducing N2O under aerobic conditions, the N2O reduction kinetics of phylogenetically diverse N2O reducers are not well understood. Here, we analyzed and compared the kinetics of clade I and clade II N2O-reducing bacteria in the presence or absence of oxygen (O2) by using a whole-cell assay with N2O and O2 microsensors. Among the seven strains tested, N2O reduction of Stutzerimonas stutzeri TR2 and ZoBell was not inhibited by oxygen (i.e., oxygen tolerant). Paracoccus denitrificans, Azospirillum brasilense, and Gemmatimonas aurantiaca reduced N2O in the presence of O2 but slower than in the absence of O2 (i.e., oxygen sensitive). N2O reduction of Pseudomonas aeruginosa and Dechloromonas aromatica did not occur when O2 was present (i.e., oxygen intolerant). Amino acid sequences and predicted structures of NosZ were highly similar among these strains, whereas oxygen-tolerant N2O reducers had higher oxygen consumption rates. The results suggest that the mechanism of O2 tolerance is not directly related to NosZ structure but is rather related to the scavenging of O2 in the cells and/or accessory proteins encoded by the nos cluster. IMPORTANCE Some bacteria can reduce N2O in the presence of O2, whereas others cannot. It is unclear whether this trait of aerobic N2O reduction is related to the phylogeny and structure of N2O reductase. The understanding of aerobic N2O reduction is critical for guiding emission control, due to the common concurrence of N2O and O2 in natural and engineered systems. This study provided the N2O reduction kinetics of various bacteria under aerobic and anaerobic conditions and classified the bacteria into oxygen-tolerant, -sensitive, and -intolerant N2O reducers. Oxygen-tolerant N2O reducers rapidly consumed O2, which could help maintain the low O2 concentration in the cells and keep their N2O reductase active. These findings are important and useful when selecting N2O reducers for bioremediation applications.


Substance P induces gastric mucosal protection at supraspinal level via increasing the level of endomorphin-2 in rats.
The aim of the present study was to analyze the potential role of substance P (SP) in gastric mucosal defense and to clarify the receptors and mechanisms that may be involved in it. Gastric ulceration was induced by oral administration of acidified ethanol in male Wistar rats. Mucosal levels of calcitonin gene-related peptide (CGRP) and somatostatin were determined by radioimmunoassay. For analysis of gastric motor activity the rubber balloon method was used. We found that central (intracerebroventricular) injection of SP (9.3-74 pmol) dose-dependently inhibited the formation of ethanol-induced ulcers, while intravenously injected SP (0.37-7.4 nmol/kg) had no effect. The mucosal protective effect of SP was inhibited by pretreatment with neurokinin 1-, neurokinin 2-, neurokinin 3- and μ-opioid receptor antagonists, while δ- and κ-opioid receptor antagonists had no effect. Endomorphin-2 antiserum also antagonized the SP-induced mucosal protection. In the gastroprotective dose range SP failed to influence the gastric motor activity. Inhibition of muscarinic cholinergic receptors, or the synthesis of nitric oxide or prostaglandins significantly reduced the effect of SP. In addition, centrally injected SP reversed the ethanol-induced reduction of gastric mucosal CGRP content. It can be concluded, that SP may induce gastric mucosal protection initiated centrally. Its protective effect is likely to be mediated by endomorphin-2, and vagal nerve may convey the centrally initiated protection to the periphery, where both prostaglandins, nitric oxide and CGRP are involved in mediating this effect.